bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Clinical Protocol for a Timely Diagnosis and Treatment of Hydrocephalus in Patients with Severe Acquired Brain Injury
Authors: Cava Francesca Cesira , Castellani Giovanna Barbara , Maietti Elisa , Salucci Pamela , Colombo Valentina , Palandri Giorgio
Published: July 2023

Background: Secondary hydrocephalus is a well-known complication of severe acquired brain injuries (sABIs) often diagnosed during inpatient rehabilitation. Currently, there is no gold standard for its detection. Therefore, we designed a novel clinical diagnostic protocol that integrates clinical, functional, biochemical and neuroradiological assessments to improve the accuracy of its diagnosis in patients with sABIs. Methods: This prospective cohort study will be conducted in a tertiary referral rehabilitation center in Italy. A historical cohort of patients will be compared with a prospective cohort undergoing the new clinical diagnostic protocol. Expected Results: The expected results include an increase in the proportion of diagnosed cases, a reduced incidence of clinical complications, an increase in the rehabilitative outcomes at discharge, a significant reduction in the length of hospital stay, and useful information about the diagnostic and prognostic value of the neuroradiological characteristics. Conclusion: We expect that this clinical diagnostic protocol will result in a more appropriate assessment and timely treatment of secondary hydrocephalus in patients with sABIs, with the ultimate goal of improving their prognosis. In addition, it could be adopted by other rehabilitation centers to improve hydrocephalus diagnosis and treatment, thereby reducing the length of hospital stay and accelerating recovery with benefits for both patients and hospitals.
Spurious Autobiographical Memory of Psychosis: A Mechanistic Hypothesis for the Resolution, Persistence, and Recurrence of Positive Symptoms in Psychotic Disorders
Authors: Chen Eric Y. H. , Wong Stephanie M. Y. , Tang Eric Y. H. , Lei Lauren K. S. , Suen Yi-nam , Hui Christy L. M.
Published: July 2023

Psychotic disorders are complex disorders with multiple etiologies. While increased dopamine synthesis capacity has been proposed to underlie psychotic episodes, dopamine-independent processes are also involved (less responsive to dopamine receptor-blocking medications). The underlying mechanism(s) of the reduction in antipsychotic responsiveness over time, especially after repeated relapses, remain unclear. Despite the consistent evidence of dopamine overactivity and hippocampal volume loss in schizophrenia, few accounts have been provided based on the interactive effect of dopamine on hippocampal synapse plasticity mediating autobiographical memory processes. The present hypothesis builds upon previous works showing the potential effects of dopamine overactivity on hippocampal-mediated neuroplasticity underlying autobiographical memory, alongside known patterns of autobiographical memory dysfunction in psychosis. We propose that spurious autobiographical memory of psychosis (SAMP) produced during active psychosis may be a key mechanism mediating relapses and treatment non-responsiveness. In a hyperdopaminergic state, SAMP is expected to be generated at an increased rate during active psychosis. Similar to other memories, it will undergo assimilation, accommodation, and extinction processes. However, if SAMP fails to integrate with existing memory, a discontinuity in autobiographical memory may result. Inadequate exposure to normalizing experiences and hyposalience due to overmedication or negative symptoms may also impede the resolution of SAMP. Residual SAMP is hypothesized to increase the propensity for relapse and treatment non-responsiveness. Based on recent findings on the role of dopamine in facilitating hippocampal synapse plasticity and autobiographical memory formation, the SAMP hypothesis is consistent with clinical observations of DUP effects, including the repetition of contents in psychotic relapses as well as the emergence of treatment non-responsiveness after repeated relapses. Clinical implications of the hypothesis highlight the importance of minimizing active psychosis, integrating psychosis memory, avoiding over-medication, and fostering normalizing experiences.
Emotional Intelligence, Innovative Work Behavior, and Cultural Intelligence Reflection on Innovation Performance in the Healthcare Industry
Authors: Binsaeed Rima H. , Yousaf Zahid , Grigorescu Adriana , Condrea Elena , Nassani Abdelmohsen A.
Published: July 2023

Innovation requires creativity, risk-taking, and the ability to manage change effectively, all of which are closely linked to emotional intelligence. Individuals with high levels of emotional intelligence are more flexible, adaptable, and resilient in technological advancements and are better able to respond effectively to new challenges and opportunities. Thus, this study aims to recognize the significant role of emotional intelligence, along with the mediation of innovative work behavior (IWB) and the moderation role of cultural intelligence in the attainment of innovation performance. This is quantitative research and for data collection, a questionnaire was used in healthcare institutions. The result shows that emotional intelligence is an antecedent of innovation performance. The finding also proved that IWB mediates the linkage between emotional intelligence and innovation performance. In addition, the outcomes show that cultural intelligence strengthens the relationship between emotional intelligence and innovation performance. However, the current dynamic business world has created an urgency to understand the linkage between the employee’s emotional intelligence and employee innovative performance, particularly taking into consideration the mediation effect of IWB. Emotional intelligence and innovation are closely linked, and innovative work behavior connects this link in a stronger way. This study offered a unique framework for achieving innovation performance through the nexus of emotional intelligence, innovative work behavior, and cultural intelligence.
How Does the Design of Consultation Pages Affect Patients’ Perception of Physician Authority and Willingness to Seek Offline Treatment: A Randomized Controlled Trial
Authors: Wang Qi , Wang Hao , Wang Si , Zhang Wen
Published: July 2023

This study aimed to assess the impact of the color and font size of a dialogue box on an online physician–patient interaction page on patients’ perceptions of the physician’s authority and their willingness to schedule an offline appointment. A 2 × 2 between-group experiment was conducted to compare the effects of two dialogue box colors (gold vs. grey) and two font sizes (large vs. regular) on patients’ perceptions. The results showed that a larger font size had a significant positive impact on patients’ perceptions of the physician’s authority, and the use of a gold-colored dialogue box also had a significant positive effect. A significant interaction was found between the dialogue box color and font size and patients’ perceptions of the physician’s authority. In addition, it was found that positive perceptions of the physician’s authority significantly affected patients’ willingness to schedule offline appointments and played a fully mediating role in the path of page design affecting offline appointment intentions. This study provides evidence that the design elements of a dialogue box—particularly, its color and font size—can influence patients’ perceptions of a physician’s authority and their willingness to schedule an offline appointment. These findings suggest that modifying the page design could improve the effectiveness of physician–patient communication.
A Fourier Series-Based Multi-Point Excitation Model for Crowd Jumping Loads
Authors: Xiong Jiecheng , Cao Zhongsui , Duan Shuqian , Cao Bei , Qian Hui , Li Chenyang
Published: July 2023

Crowd jumping loads are often simplified to a single-point excitation in the existing Fourier series-based models, most of which lack the data support of crowd jumping experiments. A Fourier series-based multi-point excitation model for crowd jumping loads is herein developed, where two parameters, the jumping frequency, and the time lag shift, are selected to quantify the crowd synchronization. After the verification of 3D motion capture technology, the probability distributions of the jumping frequency and the time lag shift are modeled based on the crowd jumping experiment, in which the trajectories of the reflective markers of 48 test subjects were simultaneously recorded by 3D motion capture technology. Through repeated sampling, the jumping load of each person in a crowd is simulated. This model could offer a useful method for evaluating the vibration performance of assembly structures like grandstands, gymnasiums, and concert venues.
Factors Hindering Solar Photovoltaic System Implementation in Buildings and Infrastructure Projects: Analysis through a Multiple Linear Regression Model and Rule-Based Decision Support System
Authors: Mustafa Mansoor , Malik Muhammad Omer Farooq
Published: July 2023

Energy plays a predominant role in the development of society. With advancements in technology and the growth of society (buildings and infrastructures), the demand for energy is rapidly increasing. Developing countries typically rely on the import of fossil fuels and capital investments in infrastructure development to meet their energy needs. The execution of solar PV projects in developing countries is currently not being implemented promisingly. Therefore, the determination of the critical success factors hindering the implementation of solar PV projects is the need of the hour. The aim of this study is to determine the factors that hinder the implementation of solar PV projects through the use of a multiple linear regression model (MLRM) and a rule-based decision support system (RBDSS). Seven categories of factors were identified through a detailed literature review and interviews with energy experts. Four hundred and twenty-nine complete responses were collected in total through a questionnaire, and they were analyzed using relative importance indexing (RII) and MLRM and RBDSS approaches. A comparison was carried out against both methodologies to determine the most critical barriers to the implementation of solar PV projects. The findings regarding the MLRM approach showed that the top seven critical factors were economic conditions, encouraging policies, technological knowledge, organizational support, social awareness, market stability, and miscellaneous aspects. Similarly, the results for the RBDSS approach identified that the top seven critical factors were encouraging policies, economic conditions, organizational support, technological knowledge, market stability, social awareness, and miscellaneous aspects. The application of MLRM and RBDSS will help stakeholders in making timely decisions and corrections during the implementation phase, providing a systematic way to support the performance and execution of solar projects.
Investigation of RC Buildings after 6 February 2023, Kahramanmaraş, Türkiye Earthquakes
Authors: Mertol Halit Cenan , Tunç Gökhan , Akış Tolga , Kantekin Yunus , Aydın İshak Can
Published: July 2023

Two major earthquakes struck Pazarcık and Elbistan, towns in Kahramanmaraş, Türkiye, on 6 February 2023, approximately 9 h apart. The first earthquake, recorded at 04:17 local time, had a Mw = 7.7, with a focal depth of 8.6 km. At 13:24 local time, a second earthquake occurred with Mw = 7.6 at a focal depth of 7 km, approximately 90 km north of the first one. A total of 11 provinces were severely affected by these earthquakes. As of 15 April 2023, they caused close to 51,000 deaths and almost 215,000 completely destroyed/severely damaged buildings. At some locations, the largest horizontal peak ground acceleration (PGA) values of the first and second earthquakes exceeded the code-generated PGAs by almost 3 and 1.75 times, respectively. A technical team visited these areas within 15 h of the first earthquake. The purpose of this article is to present their observations, findings, and the characteristics of the two earthquakes, with comprehensive site survey results supported by photographs. This study concludes that most of the collapsed and severely/moderately damaged buildings in the region were built between 1975 and 2000, when site inspections were rare or non-existent. In addition to the high PGAs recorded in these earthquakes, it was verified that the design and construction of these buildings did not fully comply with the earthquake codes valid at the time. The collapsed buildings and their damage patterns confirm inadequate development length, violation of bending stirrup ends at 135°, deficiencies in construction materials and reinforcement configuration, noncompliance with confinement zones, violation of the strong beam-stronger column analogy, and issues related to building inspection. Based on the extent of the damage, it is strongly recommended that the structural performance inspection of all other buildings located near major fault lines, specifically those constructed between 1975 and 2000, should be completed. Since these earthquakes generated much higher PGAs, which is believed to be one of the main reasons for the extensive damage, a re-evaluation of all other PGAs along major fault lines is also recommended.
Framework for a City’s Performance Assessment in the Case of an Earthquake
Authors: Koren David , Rus Katarina
Published: July 2023

A comprehensive assessment of a city’s vulnerability and resilience is a prerequisite for an effective response to a natural disaster, such as an earthquake. However, an appropriate method for assessing the seismic performance of a complex urban system is still being researched. To address this gap, the purpose of this paper is to introduce a method for seismic performance assessment of a city as a socio-physical system. Therefore, various studies of individual urban components and their interactions were combined into a holistic framework and presented in a case study of a small mid-European town. The seismic vulnerability of the building inventory was assumed or assessed based on the fragility curves adopted from the literature on similar European building stock. Seismic scenarios of different earthquake intensity (PGA of 0.15 g and 0.30 g) combined with conservative and risky approaches were applied. Considering the human perspective, urban performance was evaluated on the basis of accessibility to urban services that satisfy basic human needs (for survival and protection) via graph theory measures of global efficiency and the shortest path. The temporal aspect (before the earthquake, immediately after it, after evacuation, and after recovery) was also included to obtain a comprehensive resilience assessment. It turned out that a stronger earthquake (PGA of 0.30 g) would have far-reaching consequences for the urban performance of the investigated town, and the old city center would be particularly affected. Following the event, the system’s performance is less than half as effective compared to the initial level, indicating a sharp deterioration in the quality of life as reflected in the possibility of meeting basic human needs.
A Comparison of the Project Management Methodologies PRINCE2 and PMBOK in Managing Repetitive Construction Projects
Authors: Simonaitis Aivaras , Daukšys Mindaugas , Mockienė Jūratė
Published: July 2023

Nowadays, companies employ various project management (PM) methodologies to ensure that their projects are effective and successful. It is worth knowing that differences in principles and processes of PM methodologies influence the use of different PMs in managing non-repetitive and repetitive construction projects. This paper presents the selection and application of a rational construction PM methodology to a repetitive construction project after a comparison of two PM methodologies, namely Project Management Body of Knowledge (PMBOK) and Projects IN Controlled Environments (PRINCE2). The object of this study is a repetitive anti-corrosion works project for steel structures conducted at Company X. The research was carried out in two steps. First, a quantitative survey of the respondents from companies involved in the management and execution of construction projects was conducted with the aim to identify a rational approach to construction PM. The questionnaire consisted of fourteen closed-ended questions, six of which were generic and eight were PMBOK- and PRINCE2-specific questions. Companies that took part in the quantitative study identified the PRINCE2 project management approach as the most suitable for managing a repetitive construction project. Using the PRINCE2 PM methodology, the repetitive construction project would aim to provide as much information as possible to the project participants, form a team and assign team leaders responsible for the phases, establish a financial plan, a detailed timetable for the execution of the works, a quality control plan, and a plan of responsible persons, and detail the technological sequencing of the works. Second, a quantitative study on the selection of a rational construction project management approach for a repetitive construction project was pursued, and a qualitative assessment of construction project monitoring trends and actions was conducted. The qualitative research was performed using a structured interview method and asking the representatives of different companies X, Y, and Z the same 15 questions. The results of the qualitative research showed that a successful PM depends on the size of the project team, the PM tools and methodologies used, the PM philosophy, and the frequency of monitoring and discussing the project progress.
SBXception: A Shallower and Broader Xception Architecture for Efficient Classification of Skin Lesions
Authors: Mehmood Abid , Gulzar Yonis , Ilyas Qazi Mudassar , Jabbari Abdoh , Ahmad Muneer , Iqbal Sajid
Published: July 2023

Skin cancer is a major public health concern around the world. Skin cancer identification is critical for effective treatment and improved results. Deep learning models have shown considerable promise in assisting dermatologists in skin cancer diagnosis. This study proposes SBXception: a shallower and broader variant of the Xception network. It uses Xception as the base model for skin cancer classification and increases its performance by reducing the depth and expanding the breadth of the architecture. We used the HAM10000 dataset, which contains 10,015 dermatoscopic images of skin lesions classified into seven categories, for training and testing the proposed model. Using the HAM10000 dataset, we fine-tuned the new model and reached an accuracy of 96.97% on a holdout test set. SBXception also achieved significant performance enhancement with 54.27% fewer training parameters and reduced training time compared to the base model. Our findings show that reducing and expanding the Xception model architecture can greatly improve its performance in skin cancer categorization.
Sensory Processing in Children and Adolescents with Neurofibromatosis Type 1
Authors: Pride Natalie A. , Haebich Kristina M. , Walsh Karin S. , Lami Francesca , Rouel Melissa , Maier Alice , Chisholm Anita K. , Lorenzo Jennifer , Hearps Stephen J. C. , North Kathryn N. , Payne Jonathan M.
Published: July 2023

Despite the evidence of elevated autistic behaviors and co-occurring neurodevelopmental difficulties in many children with neurofibromatosis type 1 (NF1), we have a limited understanding of the sensory processing challenges that may occur with the condition. This study examined the sensory profile of children and adolescents with NF1 and investigated the relationships between the sensory profiles and patient characteristics and neuropsychological functioning. The parent/caregivers of 152 children with NF1 and 96 typically developing children completed the Sensory Profile 2 (SP2), along with standardized questionnaires assessing autistic behaviors, ADHD symptoms, internalizing symptoms, adaptive functioning, and social skills. Intellectual functioning was also assessed. The SP2 data indicated elevated sensory processing problems in children with NF1 compared to typically developing children. Over 40% of children with NF1 displayed differences in sensory registration (missing sensory input) and were unusually sensitive to and unusually avoidant of sensory stimuli. Sixty percent of children with NF1 displayed difficulties in one or more sensory modalities. Elevated autistic behaviors and ADHD symptoms were associated with more severe sensory processing difficulties. This first detailed assessment of sensory processing, alongside other clinical features, in a relatively large cohort of children and adolescents with NF1 demonstrates the relationships between sensory processing differences and adaptive skills and behavior, as well as psychological well-being. Our characterization of the sensory profile within a genetic syndrome may help facilitate more targeted interventions to support overall functioning.
Single-Cell Transcriptomics for Unlocking Personalized Cancer Immunotherapy: Toward Targeting the Origin of Tumor Development Immunogenicity
Authors: Khodayari Saeed , Khodayari Hamid , Saeedi Elnaz , Mahmoodzadeh Habibollah , Sadrkhah Alireza , Nayernia Karim
Published: July 2023

Cancer immunotherapy is a promising approach for treating malignancies through the activation of anti-tumor immunity. However, the effectiveness and safety of immunotherapy can be limited by tumor complexity and heterogeneity, caused by the diverse molecular and cellular features of tumors and their microenvironments. Undifferentiated tumor cell niches, which we refer to as the “Origin of Tumor Development” (OTD) cellular population, are believed to be the source of these variations and cellular heterogeneity. From our perspective, the existence of distinct features within the OTD is expected to play a significant role in shaping the unique tumor characteristics observed in each patient. Single-cell transcriptomics is a high-resolution and high-throughput technique that provides insights into the genetic signatures of individual tumor cells, revealing mechanisms of tumor development, progression, and immune evasion. In this review, we explain how single-cell transcriptomics can be used to develop personalized cancer immunotherapy by identifying potential biomarkers and targets specific to each patient, such as immune checkpoint and tumor-infiltrating lymphocyte function, for targeting the OTD. Furthermore, in addition to offering a possible workflow, we discuss the future directions of, and perspectives on, single-cell transcriptomics, such as the development of powerful analytical tools and databases, that will aid in unlocking personalized cancer immunotherapy through the targeting of the patient’s cellular OTD.
iPSC-Derived Glioblastoma Cells Have Enhanced Stemness Wnt/β-Catenin Activity Which Is Negatively Regulated by Wnt Antagonist sFRP4
Authors: Yasmin Ishmat Ara , Dharmarajan Arun , Warrier Sudha
Published: July 2023

Growing evidence indicates that cancer stem cells (CSCs) endow the tumor with stem-like properties. Recently, induced pluripotent stem cells (iPSCs) have gained increased attention because of their easy derivation and availability and their potential to differentiate into any cell type. A CSC model derived from iPSCs of human origin would help understand the driving force of tumor initiation and early progression. We report the efficient generation of feeder-free SSEA4, TRA-1-60 and TRA-1-81 positive iPSCs from amniotic membrane-derived mesenchymal stem cells (AMMSCs), which successfully differentiated into three germ layers. We then developed human iPSC-derived glioblastoma multiforme (GBM) model using conditioned media (CM) from U87MG cell line and CSCs derived from U87MG, which confer iPSCs with GBM and GSC-like phenotypes within five days. Both cell types overexpress MGMT and GLI2, but only GSCs overexpress CD133, CD44, ABCG2 and ABCC2. We also observed overexpression of LEF1 and β-catenin in both cell types. Down-regulation of Wnt antagonist secreted frizzled-related protein 4 (sFRP4) in GBM and GSCs, indicating activation of the Wnt/β-catenin pathway, which could be involved in the conversion of iPSCs to CSCs. From future perspectives, our study will help in the creation of a rapid cell-based platform for understanding the complexity of GBM.
Progress in the Preparation of Metal Oxide Electrodes for the Electrochemical Treatment of Organic Wastewater: A Short Review
Authors: Jing Xiaosheng , Wang Xinyu , Li Xiaoliang , Wang Dongqi , Xu Hao , Yan Wei
Published: July 2023

The direct discharge of untreated organic wastewater poses significant threats to the environment and to human health. To address these threats, electrocatalytic oxidation technology has emerged as a key solution for organic wastewater treatment. Building on research conducted over the past three years, this review highlights the considerable advantages of electrocatalytic oxidation technology in the context of organic wastewater treatment, with a particular emphasis on the application of metal oxide electrodes. The review also provides a summary of the primary methods used in the preparation of such electrodes. Subsequently, the applications of both single-metal-oxide electrodes and metal oxide composite electrodes in organic wastewater treatment are summarized. Finally, we discuss the future development of metal oxide electrodes.
Correction: Fleischer et al. Similarities and Differences between Site-Selective Acylation and Phosphorylation of Amphiphilic Diols, Promoted by Nucleophilic Organocatalysts Decorated with Outer-Sphere Appendages. Catalysts 2023, 13, 361
Authors: Fleischer Or , Targel Tom , Saady Fatma , Portnoy Moshe
Published: July 2023

The authors wish to make the following corrections to this paper [...]
Isomerization Properties of Pt/SAPO-11 Catalysts for the Production of Bio-Aviation Kerosene
Authors: Yang Sangni , Liu Xuejun , Zhang Xin , Sun Wuji , Ma Qiqi , Song Nianhua , Lu Meizhen , Hu Jianming
Published: July 2023

The hydroisomerization of n-alkanes is an important step in the production of high-quality bio-aviation kerosene. A SAPO-11 molecular sieve was synthesized using the hydrothermal synthesis method, and a 0.5 wt% Pt/SAPO-11 catalyst was prepared using the impregnation method. The crystal phase, pore structure, acidity, and morphology of Pt/SAPO-11 were characterized via X-ray diffraction, N2 adsorption-desorption, NH3 temperature-programmed desorption, scanning electron microscopy, and transmission electron microscopy, respectively. The hydroisomerization performance of the catalyst was evaluated with bio-n-hexadecane as the model compound. The results showed that temperature and space velocity had significant effects. Under the conditions of 340 °C, 1.5 MPa, WHSV = 1.0 h−1, V(H2): V(n-hexadecane) = 1000:1, the conversion of n-hexadecane and the selectivity of i-hexadecane were 81.8% and 86.5%, respectively.
Deep Learning-Based Computational Cytopathologic Diagnosis of Metastatic Breast Carcinoma in Pleural Fluid
Authors: Park Hong Sik , Chong Yosep , Lee Yujin , Yim Kwangil , Seo Kyung Jin , Hwang Gisu , Kim Dahyeon , Gong Gyungyub , Cho Nam Hoon , Yoo Chong Woo , Choi Hyun Joo
Published: July 2023

A Pleural effusion cytology is vital for treating metastatic breast cancer; however, concerns have arisen regarding the low accuracy and inter-observer variability in cytologic diagnosis. Although artificial intelligence-based image analysis has shown promise in cytopathology research, its application in diagnosing breast cancer in pleural fluid remains unexplored. To overcome these limitations, we evaluate the diagnostic accuracy of an artificial intelligence-based model using a large collection of cytopathological slides, to detect the malignant pleural effusion cytology associated with breast cancer. This study includes a total of 569 cytological slides of malignant pleural effusion of metastatic breast cancer from various institutions. We extracted 34,221 augmented image patches from whole-slide images and trained and validated a deep convolutional neural network model (DCNN) (Inception-ResNet-V2) with the images. Using this model, we classified 845 randomly selected patches, which were reviewed by three pathologists to compare their accuracy. The DCNN model outperforms the pathologists by demonstrating higher accuracy, sensitivity, and specificity compared to the pathologists (81.1% vs. 68.7%, 95.0% vs. 72.5%, and 98.6% vs. 88.9%, respectively). The pathologists reviewed the discordant cases of DCNN. After re-examination, the average accuracy, sensitivity, and specificity of the pathologists improved to 87.9, 80.2, and 95.7%, respectively. This study shows that DCNN can accurately diagnose malignant pleural effusion cytology in breast cancer and has the potential to support pathologists.
Mathematical Modeling of Clonal Interference by Density-Dependent Selection in Heterogeneous Cancer Cell Lines
Authors: Veith Thomas , Schultz Andrew , Alahmari Saeed , Beck Richard , Johnson Joseph , Andor Noemi
Published: July 2023

Many cancer cell lines are aneuploid and heterogeneous, with multiple karyotypes co-existing within the same cell line. Karyotype heterogeneity has been shown to manifest phenotypically, thus affecting how cells respond to drugs or to minor differences in culture media. Knowing how to interpret karyotype heterogeneity phenotypically would give insights into cellular phenotypes before they unfold temporally. Here, we re-analyzed single cell RNA (scRNA) and scDNA sequencing data from eight stomach cancer cell lines by placing gene expression programs into a phenotypic context. Using live cell imaging, we quantified differences in the growth rate and contact inhibition between the eight cell lines and used these differences to prioritize the transcriptomic biomarkers of the growth rate and carrying capacity. Using these biomarkers, we found significant differences in the predicted growth rate or carrying capacity between multiple karyotypes detected within the same cell line. We used these predictions to simulate how the clonal composition of a cell line would change depending on density conditions during in-vitro experiments. Once validated, these models can aid in the design of experiments that steer evolution with density-dependent selection.
BDNF/TrkB Is a Crucial Regulator in the Inflammation-Mediated Odontoblastic Differentiation of Dental Pulp Stem Cells
Authors: Kim Ji-Hyun , Irfan Muhammad , Hossain Md Akil , George Anne , Chung Seung
Published: July 2023

The odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there is a link between inflammation and dental tissue regeneration, identified via enhanced DPSC-mediated dentinogenesis in vitro. Brain-derived neurotrophic factor (BDNF) is a nerve growth factor-related gene family molecule which functions through tropomyosin receptor kinase B (TrkB). While the roles of BDNF in neural tissue repair and other regeneration processes are well identified, its role in dentinogenesis has not been explored. Furthermore, the role of BDNF receptor-TrkB in inflammation-induced dentinogenesis remains unknown. The role of BDNF/TrkB was examined during a 17-day odontogenic differentiation of DPSCs. Human DPSCs were subjected to odontogenic differentiation in dentinogenic media treated with inflammation inducers (LTA or TNFα), BDNF, and a TrkB agonist (LM22A-4) and/or antagonist (CTX-B). Our data show that BDNF and TrkB receptors affect the early and late stages of the odontogenic differentiation of DPSCs. Immunofluorescent data confirmed the expression of BDNF and TrkB in DPSCs. Our ELISA and qPCR data demonstrate that TrkB agonist treatment increased the expression of dentin matrix protein-1 (DMP-1) during early DPSC odontoblastic differentiation. Coherently, the expression levels of runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) were increased. TNFα, which is responsible for a diverse range of inflammation signaling, increased the levels of expression of dentin sialophosphoprotein (DSPP) and DMP1. Furthermore, BDNF significantly potentiated its effect. The application of CTX-B reversed this effect, suggesting TrkB`s critical role in TNFα-mediated dentinogenesis. Our studies provide novel findings on the role of BDNF-TrkB in the inflammation-induced odontoblastic differentiation of DPSCs. This finding will address a novel regulatory pathway and a therapeutic approach in dentin tissue engineering using DPSCs.
Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids
Authors: Park Dongil , Lee Dahye , Kim Yoonjoo , Park Yeonhee , Lee Yeon-Jae , Lee Jeong Eun , Yeo Min-Kyung , Kang Min-Woong , Chong Yooyoung , Han Sung Joon , Choi Jinwook , Park Jong-Eun , Koh Yongjun , Lee Jaehyeok , Park YongKeun , Kim Ryul , Lee Jeong Seok , Choi Jimin , Lee Sang-Hyun , Ku Bosung , Kang Da Hyun , Chung Chaeuk
Published: July 2023

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.
Targeting Prohibitins to Inhibit Melanoma Growth and Overcome Resistance to Targeted Therapies
Authors: Najem Ahmad , Krayem Mohammad , Sabbah Serena , Pesetti Matilde , Journe Fabrice , Awada Ahmad , Désaubry Laurent , Ghanem Ghanem E.
Published: July 2023

Despite important advances in the treatment of metastatic melanoma with the development of MAPK-targeted agents and immune checkpoint inhibitors, the majority of patients either do not respond to therapies or develop acquired resistance. Furthermore, there is no effective targeted therapy currently available for BRAF wild-type melanomas (approximately 50% of cutaneous melanoma). Thus, there is a compelling need for new efficient targeted therapies. Prohibitins (PHBs) are overexpressed in several types of cancers and implicated in the regulation of signaling networks that promote cell invasion and resistance to cell apoptosis. Herein, we show that PHBs are highly expressed in melanoma and are associated with not only poor survival but also with resistance to BRAFi/MEKi. We designed and identified novel specific PHB inhibitors that can inhibit melanoma cell growth in 3D spheroid models and a large panel of representative cell lines with different molecular subtypes, including those with intrinsic and acquired resistance to MAPKi, by significantly moderating both MAPK (CRAF-ERK axis) and PI3K/AKT pathways, and inducing apoptosis through the mitochondrial pathway and up-regulation of p53. In addition, autophagy inhibition enhances the antitumor efficacy of these PHB ligands. More important, these ligands can act in synergy with MAPKi to more efficiently inhibit cell growth and overcome drug resistance in both BRAF wild-type and mutant melanoma. In conclusion, targeting PHBs represents a very promising therapeutic strategy in melanoma, regardless of mutational status.
Neutrophil Extracellular Traps Drive Dacryolithiasis
Authors: Zlatar Leticija , Timm Thomas , Lochnit Günter , Bilyy Rostyslav , Bäuerle Tobias , Munoz-Becerra Marco , Schett Georg , Knopf Jasmin , Heichel Jens , Ali Mohammad Javed , Schapher Mirco , Paulsen Friedrich , Herrmann Martin
Published: July 2023

Mucopeptide concretions, previously called dacryoliths, are macroscopic stones that commonly obstruct the lacrimal sac. The mechanism behind dacryolithiasis remains unclear; however, the involvement of various immune cells, including neutrophils, has been confirmed. These findings remain limited, and no information on neutrophil extracellular traps (NETs), essentially involved in the pathogenesis of other lithiases, is available yet. Here, we employ microcomputed tomography, magnetic resonance tomography, histochemistry, mass spectrometry, and enzyme activity analyses to investigate the role of neutrophils and NETs in dacryolithiasis. We classify mucopeptide concretions into three types, with respect to the quantity of cellular and acellular material, polysaccharides, and mucosubstances. We propose the role of neutrophils and NETs within the existing model of gradual formation and growth of mucopeptide concretions, with neutrophils contributing to the initial stages of dacryolithiasis, as they localized on the inner (older) parts of the tissue. As NETs localized on the outer (newer) parts of the tissue, we link their role to the late stages of dacryolithiasis, presumably maintaining the proinflammatory environment and preventing efficient clearance. An abundance of IgG on the surface indicates the involvement of the adaptive immune system later as well. These findings bring new perspectives on dacryolithiasis, in which the innate and adaptive immune system are essentially involved.
Redefining Precision Management of r/r Large B-Cell Lymphoma: Novel Antibodies Take on CART and BMT in the Quest for Future Treatment Strategies
Authors: Dada Reyad
Published: July 2023

The treatment paradigms for patients with relapsed large B-cell lymphoma are expanding. Chimeric antigen receptor technology (CAR-T) has revolutionized the management of these patients. Novel bispecific antibodies and antibody–drug conjugates, used as chemotherapy-free single agents or in combination with other novel therapeutics, have been quickly introduced into the real-world setting. With such a paradigm shift, patients have an improved chance of better outcomes with unpredictable complete remission rates. Additionally, the excellent tolerance of new antibodies targeting B-cell lymphomas is another motivation to broaden its use in relapsed and refractory patients. With the increasing number of approved therapy approaches, future research needs to focus on optimizing the sequence and developing new combination strategies for these antibodies, both among themselves and with other agents. Clinical, pathological, and genetic risk profiling can assist in identifying which patients are most likely to benefit from these costly therapeutic options. However, new combinations may lead to new side effects, which we must learn to deal with. This review provides a comprehensive overview of the current state of research on several innovative antibodies for the precision management of large B-cell lymphoma. It explores various treatment strategies, such as CAR-T vs. ASCT, naked antibodies, antibody–drug conjugates, bispecific antibodies, and bispecific T-cell engagers, as well as discussing the challenges and future perspectives of novel treatment strategies. We also delve into resistance mechanisms and factors that may affect decision making. Moreover, each section provides a detailed analysis of the available literature and ongoing clinical trials.
C2O Nanotubes with Negative Strain Energies and Improvements of Thermoelectric Properties via N-Doping Predicted from First-Principle Calculations
Authors: Wu Jianbao , Jiang Liyuan , Li Xiaoyi , Yin Zhixiang
Published: July 2023

In this study, the geometric structure, strain energy, and electronic properties of armchair C2O nanotubes (A_C2ONTs(n,n)) and zigzag C2O nanotubes  (Z_C2ONTs(n,0)) are studied in detail. The results show that these nanotubes behave as special shapes; the section of Z_C2ONTs(n,0) along the axial direction is an n-edge type, and the section tends to be round with an increase in n while the boundary of section along the axial direction for A_C2ONTs(n,n) fluctuates. With an increase in n, the fluctuation disappears gradually, and the section also tends to be round. Compared with C2O nanosheets (g_C2O), C2O nanotubes have similar or even smaller strain energy, when the tube diameter is greater than or equal to 15 Å, the strain energy begins to show a negative value, and the negative value tends to be stable as the pipe diameter increases. Z_C2ONTs start to show negative strain energies from n = 8 and A_C2ONTs from n = 12, indicating their higher stabilities relative to the g_C2O sheets. The calculation of the electronic band structure shows that Z_C2ONTs are an indirect band gap semiconductor, and A_C2ONT is a direct band gap semiconductor. The band gap value of Z_C2ONTs first increases and then stabilizes with the diameters of the nanotubes, and the band gap value of A_C2ONTs decreases with the increase in the nanotubes and tends to the band gap value of the g_C2O sheet. In addition, the electronic properties and thermoelectric properties of C2ONTs(n=4,6,8) before and after N-doping were also studied. We found that N-doping changed the electronic and thermoelectric properties of C2ONTs. It reduced the nanotube band gap value and significantly improved the thermoelectric figures of merit of Z_C2ONTs(n=4,6,8) and A_C2ONT(4,4), which comprised an effective strategy to improve the thermoelectric figure of merit of nanotubes. The results showed that the C2ONTs had potential as thermoelectric materials after N-doping, which provided important guidance for designing low-dimensional g_C2O nanostructures.
Synthesis, Crystal Structure, and Computational Investigations of 2-(2-(4-Fluorophenyl)-2-oxoethyl)-6-methyl-5-(4-methylbenzyl)pyridazin-3(2H)-one as Antiviral Agent
Authors: El Kalai Fouad , Abraham Christina Susan , Kansiz Sevgi , Oulmidi Afaf , Muthu Sambantham , Prasana Johanan Christian , Dege Necmi , Abuelizz Hatem A. , Al-Salahi Rashad , Benchat Noureddine , Karrouchi Khalid
Published: July 2023

The aim of this work was to scrutinize the physiochemical properties of a new pyridazin-3(2H)-one derivative with potential pharmaceutical effectiveness via density functional theory (DFT) and molecular docking analysis. The compound 2-(2-(4-fluorophenyl)-2-oxoethyl)-6-methyl-5-(4-methylbenzyl)pyridazin-3(2H)-one (FOMMP) was synthesized and characterized by FT-IR, UV-Vis, 1H-NMR, 13C-NMR, ESI-MS, and single-crystal XRD analysis. In addition, the geometrical structure of the molecule was analyzed. Frontier molecular orbital (FMO) analysis showed a low energy gap that suggests the chemical reactivity of the title compound. The electrophilicity index (ω) points towards the probable biological activity of FOMMP. The molecular electrostatic potential (MEP) was used to assess the local reactivity properties and suggests that the nitrogen atom sites are electronegative. Computational and experimental UV-spectral analyses were performed to attain the bandgap associated with electronic transitions while the charge transfer length helped us determine that the excitation mode associated with the electronic transitions is long-ranged. Natural hybrid orbital (NHO) and natural bond orbital (NBO) analyses depicted the prominent acceptor-donor interactions in terms of the stabilization energies. Hirshfeld surface analysis was performed to analyze the intermolecular interactions in the crystal structure. In addition, a molecular docking study was executed to evaluate the potential of the protease inhibitors (PIs) against SARS-CoV-2.
Advanced Energetic Materials: Testing and Modeling
Authors: Liu Rui , Wen Yushi , Pang Weiqiang
Published: July 2023

Energetic Materials (EMs) are a traditional branch of materials [...]
Radiation-Induced Oropharyngeal Squamous Cell Carcinoma: Case Report and Review of the Literature
Authors: Giannini Lorenzo , Alliata Andrea , Cristofaro Valentina , Incandela Fabiola , Pompilio Madia , Ottini Arianna , Cavalieri Stefano , Nuzzolese Imperia , Iacovelli Nicola Alessandro , Franceschini Marzia , Deganello Alberto
Published: July 2023

Background: Radiation therapy (RT) is a mainstay for the treatment of head and neck (HN) cancers, with 80% of patients receiving such treatment. Radiation-induced malignancies represent a life-threatening long-term effect of RT, with an incidence of 0.5% to 15%. Case Description: After 13 years, a 33-year-old woman treated with chemo-radiotherapy for nasopharyngeal carcinoma developed a locally advanced, radiation-induced, p16-negative oropharyngeal squamous cell carcinoma (SCC) at the base of the tongue. Chemo/immunotherapy was administered as a first-line treatment. Given the optimal response and the feasibility of surgery, after three cycles, the patient underwent a total glossectomy, bilateral neck dissection, and reconstruction with a thoraco-dorsal free flap. A histological examination found SCC with a residual cancer burden of 70% and free margins. Discussion: The mechanisms responsible for carcinogenesis after RT are still not completely clear. Diagnosis may be challenging due to the previous treatment; growth patterns are unusual, and lymphotropism is lower. Prognosis is usually poor since surgical resectability is often not achievable. Conclusions: Radiation-induced malignancies are difficult to treat. Patient management should always be discussed at a multidisciplinary level. Future research is needed to assess whether the promising results of clinical studies with pre-operative immunotherapy in locally advanced HN SCC patients may be translated into radiation-induced cancers.