bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase Correction Model for Fourier Transform Spectroscopy
Authors: Cheng Huishi , Shen Honghai , Meng Lingtong , Ben Chenzhao , Jia Ping
Published: February 2024

In Fourier transform spectroscopy (FTS), the conventional Mertz method is commonly used to correct phase errors of recovered spectra, but it performs poorly in correcting nonlinear phase errors. This paper proposes a phase correlation method–all-pass filter (PCM-APF) model to correct phase errors. In this model, the proposed improved phase correlation method can correct linear phase errors, and all-pass filters are applied to correct the residual nonlinear phase errors. The optimization algorithm for the digital all-pass filters employs an improved algorithm which combines the subtraction-average-based optimizer (SABO) and the golden sine algorithm (Gold-SA). The proposed PCM-APF model demonstrates high correction precision, and the optimization algorithm for the filters converges faster than traditional intelligent optimization algorithms.
On the Variation of Cup Anemometer Performance Due to Changes in the Air Density
Authors: Alfonso-Corcuera Daniel , Meseguer-Garrido Fernando , Torralbo-Gimeno Ignacio , Pindado Santiago
Published: February 2024

In the present paper, the effect of air density variations on cup anemometer performance is analyzed. The effect on the sensor’s performance is mainly due to the difference between the altitude at which the cup anemometer is working and the altitude at which this instrument was calibrated. Data from the available literature are thoroughly analyzed, focusing on explaining the coupled effect of the air temperature on both the rotor’s friction torque and the air density (that is, related to the aerodynamic torque on the rotor). As a result, the effect of air density variation at constant temperature (that is, leaving aside any variation of friction forces at the anemometer rotor shaft) on the sensor transfer function (i.e., on the calibration constants) is evaluated. The analysis carried out revealed a trend change in the variation with air density of the transfer function of the cup anemometer. For densities greater than 0.65, the calibration constants of the instrument have a variation with density that must necessarily change suddenly as the start-up speed, represented by the calibration constant B, becomes zero around this value of air density. To highlight the relevance of the present research, some estimations of the effect of wind speed measurement errors associated with air density changes on the Annual Energy Production (AEP) of wind turbines are included. A 1.5% decrease in the AEP forecast at air density corresponding to 2917 m above sea level is estimated for 3000–4500 kW wind turbines.
Adjuvant Effects of Lavandula angustifolia Oil in Experimental Carrageenan-Induced Thrombosis
Authors: But Valeriu Mihai , Rus Vasile , Ilyés Tamás , Gherman Mădălina Luciana , Stănescu Ioana Cristina , Bolboacă Sorana D. , Bulboacă Adriana Elena
Published: February 2024

Antinociceptive, sedative, anti-inflammatory, and antioxidant effects of lavender oil (LO) have been documented. The aim of our study was to evaluate the adjuvant effects of pretreatment with LO compared to standard treatment (low molecular weight heparin) in thrombosis. We evaluated the effects of two doses of LO in addition to nadroparin calcium (NC) on experimentally induced thrombosis in rats. The groups were as follows: the control (C) group received intraperitoneal (i.p.) saline and vehicle (DMSO), the thrombosis (T) group received saline plus vehicle pretreatment, nadroparin calcium (NC) was administrated subcutaneously (s.c.), TNCL1 and TNCL2 received pretreatment with LO (TNCL1—100 mg/kg body weight (b.w.) i.p. and TNCL2—200 mg/kg b.w. i.p. and NC s.c.). Thrombosis was successfully obtained in all groups, except the C group. Statistically significant differences between groups (p-values < 0.001) were found for the levels of oxidative stress biomarkers (malondialdehyde, nitric oxide, and total oxidative stress) and antioxidant parameters (total antioxidant capacity and thiols), TNF-α, MCP-1, and RANTES. Dose-dependent effects are seen on the biomarkers under evaluation, with higher LO doses producing the best outcomes. When compared to the group receiving standard treatment (NC alone), the LO pretreatment led to an increase in antioxidant levels (p-values < 0.001) and a decrease in oxidative stress and pro-inflammatory levels (p-values < 0.001). Lavender oil associated with NC treatment alleviates the inflammatory components of experimental carrageenan-induced thrombosis in rats by decreasing oxidative stress and inflammatory cytokines and improving antioxidant activity.
Attributes Required by Physiotherapists to Increase Adoption and Implementation of Practice Management Software: A Qualitative Study Using Focus Groups
Authors: Arza-Moncunill Eduardo , Martín-San Agustín Rodrigo , Moreno-Seguro Noemí , Escriche-Escuder Adrián , Medina-Mirapeix Francesc
Published: February 2024

(1) Background: The aim of this study was to identify the practice management software (PMS) attributes required by physiotherapists to improve software design and development in order to increase the adoption and implementation of software and minimize the impact on the workflow of the clinic. (2) Methods: In total, 27 graduated physiotherapists with clinical and management expertise and experience in management software for physiotherapy services participated in six focus groups. Research staff members recorded, transcribed, and analyzed the focus groups, using a thematic analysis to code and classify the comments. (3) Results: A total of 43 categories of coded statements divided into 12 subthemes and five broad themes were identified and compiled in two core areas of content: clinical care and administrative tasks. In order to improve the adoption and implementation of physiotherapy PMS, this research provides experiential knowledge on the inefficiencies perceived by physiotherapists regarding current software programs and the specific attributes to assist practice management and facilitate workflows. The focus group analyses led us to map the multifaceted framework for physiotherapy PMS. (4) Conclusion: These findings provide valuable information as to what aspects are meaningful for the future design and development of physiotherapy PMS, thus providing guidance to both software developers and to end-users when benchmarking software solutions.
Analyzing and Discovering Spatial Algorithm Complexity Vulnerabilities in Recursion
Authors: Wang Ziqi , Bu Debao , Tian Weihan , Cui Baojiang
Published: February 2024

The algorithmic complexity vulnerability (ACV) that may lead to denial of service attacks greatly disrupts the security and availability of applications, and due to the widespread use of third-party libraries, its impact may be amplified through the software supply chain. The existing work in the field is dedicated to abstract loop or iterative patterns and fuzzing the entire application to discover algorithm complexity vulnerabilities, but they still face efficiency and effectiveness issues. Our research focuses on: (1) proposing a representation and extraction method for code features related to algorithmic complexity vulnerabilities, helping analysts quickly understand program logic; (2) providing a new ACV detecting model, focusing on the spatial complexity anomalies caused by deep recursion structures, and proposing a new filtering method; and (3) aiming at the difficulty of efficiently generating complex-data-type-related payloads using existing symbol execution techniques, a call-chain-guided payload construction method is proposed. We tested third-party components in the open-source Java Maven Repository, identified many unexposed vulnerabilities, and eight of them received Common Vulnerabilities and Exposures (CVE) identifiers, and demonstrated that our method can discover more algorithmic complexity vulnerabilities compared to existing tools with better performance.
Sensitive Areas’ Observation Simulation Experiments of Typhoon “Chaba” Based on Ensemble Transform Sensitivity Method
Authors: Ao Yanlong , Zhang Yu , Shao Duanzhou , Zhang Yinhui , Tang Yuan , Hu Jiazheng , Zhang Zhifei , Sun Yuhan , Lyu Peining , Yu Qing , He Ziyan
Published: February 2024

High-impact weather (HIW) events, such as typhoons, usually have sensitive regions where additional observations can be deployed and sensitive observations assimilated, which can improve forecasting accuracy. The ensemble transform sensitivity (ETS) method was employed to estimate the sensitive regions in the “Chaba” case in order to explore the impact of observation data in sensitive areas on typhoon forecasting during the rapid intensification phase. A set of observation system simulation experiments were conducted, with assimilations of sensitive observations (SEN), randomly selected observations (RAN), whole domain observations (ALL), and no assimilation (CTRL). The results show that (1) the sensitive areas of Typhoon “Chaba” are primarily located in the southwest of the typhoon center and are associated with the distribution of the wind field structure; (2) the typhoon intensity and tracks simulated by the SEN and RAN experiments are closer to the truth than the CTRL; (3) the SEN experiment, with only 3.6% of assimilated data observations, is comparable with the ALL experiment during the rapid intensification phase of the typhoon; (4) the uncertainty of the mesoscale model can be improved by capturing large-scale vertical wind shear and vorticity features from the GEFS data and then using the data assimilation method, which makes the vertical shear and vorticity field more reasonable.
Long-Lived Levels in Multiply and Highly Charged Ions
Authors: Träbert Elmar
Published: February 2024

Atoms and ions remain in some long-lived excited levels for much longer than in typical “normal” levels, but not forever. Various cases of this so-called metastability that occur in multiply or even highly charged ions are discussed in a tutorial review, as well as examples of atomic lifetime measurements on such levels, their intentions, and some present and future applications.
Intraoperative Measurement of Insertion Speed in Cochlear Implant Surgery: A Preliminary Experience with Cochlear SmartNav
Authors: Concheri Stefano , Brotto Davide , Ariano Marzia , Daloiso Antonio , Di Pasquale Fiasca Valerio Maria , Sorrentino Flavia , Coppadoro Beatrice , Trevisi Patrizia , Zanoletti Elisabetta , Franchella Sebastiano
Published: February 2024

Objectives: The objectives were to present the real-time estimated values of cochlear implant (CI) electrode insertion speed (IS) during intraoperative sessions using the Cochlear Nucleus SmartNav System to assess whether this measure affected CI outcomes and to determine whether real-time feedback assists expert surgeons in achieving slow insertion. Methods: The IS was measured in 52 consecutive patients (65 implanted ears) using the CI632 electrode. The IS values were analyzed in relation to procedure repetition over time, NRT ratio, and CI audiological outcomes. Results: The average IS was 0.64 mm/s (SD = 0.24); minimum and maximum values were 0.23 and 1.24 mm/s, respectively. The IS significantly decreased with each array insertion by the operator (p = 0.006), and the mean decreased by 24% between the first and last third of procedures; however, this reduction fell within the error range of SmartNav for IS (+/−0.48 mm/s). No correlation was found between IS and the NRT ratio (p = 0.51), pure-tone audiometry (PTA) at CI activation (p = 0.506), and PTA (p = 0.94) or word recognition score (p = 0.231) at last evaluation. Conclusions: The estimated IS reported by SmartNav did not result in a clinically significant reduction in insertion speed or an improvement in CI hearing outcomes. Real-time feedback of IS could potentially be used for training, but its effectiveness requires confirmation through additional studies and more accurate tools. Implementation of IS assessment in clinical practice will enable comparisons between measurement techniques and between manual and robot-assisted insertions. This will help define the optimal IS range to achieve better cochlear implant (CI) outcomes.
Some Properties of Zipf’s Law and Applications
Authors: Bolea Speranta Cecilia , Pirnau Mironela , Bejinariu Silviu-Ioan , Apopei Vasile , Gifu Daniela , Teodorescu Horia-Nicolai
Published: February 2024

The article extends the theoretical and applicative analysis of Zipf’s law. We are concerned with a set of properties of Zipf’s law that derive directly from the power law expression and from the discrete nature of the objects to which the law is applied, when the objects are words, lemmas, and the like. We also search for variations of Zipf’s law that can help explain the noisy results empirically reported in the literature and the departures of the empirically obtained nonlinear graph from the theoretical linear one, with the variants analyzed differing from Mandelbrot and lognormal distributions. A problem of interest that we deal with is that of mixtures of populations obeying Zipf’s law. The last problem has relevance in the analysis of texts with words with various etymologies. Computational aspects are also addressed.
Regression Metamodel-Based Digital Twin for an Industrial Dynamic Crossflow Filtration Process
Authors: Heusel Matthias , Grim Gunnar , Rauhut Joel , Franzreb Matthias
Published: February 2024

Dynamic crossflow filtration (DCF) is the state-of-the-art technology for solid–liquid separation from viscous and sensitive feed streams in the food and biopharma industry. Up to now, the potential of industrial processes is often not fully exploited, because fixed recipes are usually applied to run the processes. In order to take the varying properties of biological feed materials into account, we aim to develop a digital twin of an industrial brownfield DCF plant, allowing to optimize setpoint decisions in almost real time. The core of the digital twin is a mechanistic–empirical process model combining fundamental filtration laws with process expert knowledge. The effect of variation in the selected process and model parameters on plant productivity has been assessed using a model-based design-of-experiments approach, and a regression metamodel has been trained with the data. A cyclic program that bidirectionally communicates with the DCF asset serves as frame of the digital twin. It monitors the process dynamics membrane torque and transmembrane pressure and feeds back the optimum permeate flow rate setpoint to the physical asset in almost real-time during process runs. We considered a total of 24 industrial production batches from the filtration of grape juice from the years 2022 and 2023 in the study. After implementation of the digital twin on site, the campaign mean productivity increased by 15% over the course of the year 2023. The presented digital twin framework is a simple example how an industrial established process can be controlled by a hybrid model-based algorithm. With a digital process dynamics model at hand, the presented metamodel optimization approach can be easily transferred to other (bio)chemical processes.
Characteristics of Developmental and Epileptic Encephalopathy Associated with PACS2 p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature
Authors: Stoian Adina , Bajko Zoltan , Bălașa Rodica , Andone Sebastian , Stoian Mircea , Ormenișan Ioana , Muntean Carmen , Bănescu Claudia
Published: February 2024

Background: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. Methods: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. Results: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs’ involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. Conclusions: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.
Mediating and Moderating Effects of Uncertainty on the Relationship between Family Function, Self-Care, and Depression among Blood Cancer Survivors
Authors: Yeom Hyun-E , Park Da-Som
Published: February 2024

Uncertainty in cancer survivorship poses a substantial challenge to survivors’ coping mechanisms and psychological well-being. This study investigated the intricate interplay among family function, uncertainty, self-care, and depression in this context, with a primary focus on discerning the mediating and moderating roles of uncertainty in the relationship between family function, self-care, and depression among blood cancer survivors. Cross-sectional data from 147 survivors in South Korea underwent analysis using descriptive statistics, Pearson’s correlations, and the PROCESS macro in SPSS version 26.0. The results revealed that family function significantly predicted both self-care and depression. Notably, uncertainty mediated the relationship between family function and these outcomes. Furthermore, the impact of family function on depression was moderated by uncertainty, indicating a relatively weaker association in survivors facing higher uncertainty levels. This study contributes valuable insights by elucidating the role of uncertainty in regulating how family function influences self-care and depression among survivors of blood cancer. It emphasizes the critical need to enhance family function and alleviate uncertainty for the improved adjustment of cancer survivorship. The findings underscore the importance of targeted support for individuals grappling with different levels of uncertainty, aiming to prevent or mitigate depressive symptoms through the reinforcement of family function.
Nature of Occupational Incidents among Roofing Contractors: A Data Mining Approach
Authors: Onuchukwu Ikechukwu Sylvester , Gholizadeh Pouya , Liko Gentian , Esmaeili Behzad
Published: February 2024

Given that roofing contractors in the construction industry have the highest fatality rate among specialty contractors, understanding the root cause of incidents among roofers is critical for improving safety outcomes. This study applied frequency analysis and decision tree data-mining techniques to analyze roofers’ fatal and non-fatal accident reports. The frequency analysis yielded insights into the leading cause of accidents, with fall to a lower level (83%) being the highest, followed by incidence sources relating to structures and surfaces (56%). The most common injuries experienced by roofing contractors were fractures (49%) and concussions (15%), especially for events occurring in residential buildings, maintenance and repair works, small projects (i.e., $50,000 or less), and on Mondays. According to the decision tree analysis, the most important factor for determining the nature of the injury is the nonfragile injured body part, followed by injury caused by coating works. The decision tree also produced decision rules that provide an easy interpretation of the underlying association between the factors leading to incidents. The decision tree models developed in this study can be used to predict the nature of potential injuries for strategically selecting the most effective injury-prevention strategies.
Investigating the Influence of the Improved Multibody Rope Approach on the Structural Behavior of Dakar Mosque Gridshell Structure
Authors: Melchiorre Jonathan , Invernizzi Stefano , Manuello Bertetto Amedeo
Published: February 2024

Gridshell structures are characterized by an impressive strength-to-weight ratio, allowing their application in large-span roofing structures. However, their complex construction process and maintenance limited their widespread application. In recent years, the development of parametric and computational design tools has rekindled interest in this type of structure. Among these techniques, the Multibody Rope Approach (MRA) is a form-finding method based on the dynamic equilibrium of a system of masses (nodes) connected by ropes, which allows optimizing the structural shape starting from the dual geometry of the funicular network. To optimize the construction process, an improved version of the MRA, i-MRA, has been recently developed by the authors with the goal of uniforming the size of the structural components. To investigate the impact of the i-MRA method on the structural behavior of gridshell structures, the practical case of the design of a mosque roof is here analyzed. The comparison is carried out in terms of structural performance with respect to permanent and equivalent quasi-static loads. In addition, free-vibration natural-frequency shift is obtained by performing linear modal analysis. Finally, the global behavior with respect to buckling and elastic instability is assessed solving the relevant eigenvalue problem. The results demonstrate that for the roofing of the Dakar mosque, the structural configuration obtained through i-MRA is superior in terms of both construction efficiency and structural performance. The achieved shape exhibits a more uniform distribution of stresses induced by the applied loads together with very limited structural element typologies.
Analysis of Mechanical Response of Epoxy Asphalt-Repaired Pavement in Pothole Interface on Steel Bridge Deck under Coupled Temperature-Dynamic Loading
Authors: Zhuang Yizhou , Liu Kai , Zhan Xiaoli
Published: February 2024

The persistence of pothole maintenance represents an enduring challenge. Past studies have largely concentrated on the materials and techniques used for remediation, with a lack of attention given to the pothole interface. This paper employed epoxy asphalt rubber (EAR-10) as the repair material, exploring the impact of coupled temperature-dynamic loading on the mechanical response of the interface. Finite element modelling (FEM), adopting the viscoelastic characteristics of EAR-10, was deployed to investigate the mechanical response of the interface under three temperature service conditions high, medium, and low when a dynamic load traversed the pothole. The stress variations in the interface at various inclinations and thicknesses of the repair blocks were also studied. In addition, the comparative analysis of high-temperature rut resistance for powdered rubber composite-modified asphalt and SBS modified asphalt was conducted via the multiple stress examination in terms of its high-temperature resilience, resistance to moisture-induced damage, and fatigue life by employing the asphalt mixture rutting test, low-temperature bending test on small beams, and the water immersion Marshall stability test, respectively. The repair efficacy of EAR-10 was appraised through post-repair water immersion rutting tests and bending tests on composite structural small beams. The results indicated that incorporating coupled temperature-dynamic loading led to a considerable increase in stress, particularly under low-temperature service conditions. An inclination angle of 30 degrees was found to be optimal for the interface. The research methodology presented here is pertinent to guiding the pothole repair in the steel bridge pavement, ensuring the strength and durability of the interface rivals that of newly constructed layers.
Assessing the Digital Transformation Readiness of the Construction Industry Utilizing the Delphi Method
Authors: Naji Khalid K. , Gunduz Murat , Alhenzab Fahid , Al-Hababi Hamed , Al-Qahtani Abdulla
Published: February 2024

The rapid advancement of digital technology has enabled digital transformation across various sectors, including construction. The construction industry has long been associated with conventional, labor-intensive practices that can adversely influence the entire construction process. However, this culture is changing as key players in the sector are progressively identifying and embracing the vast opportunities and associated benefits of using digital tools and technologies to improve the performance and outcomes of the overall project lifecycle. To this end, this study uses the Delphi technique to identify 70 factors that contribute to the digital transformation of the construction industry, categorizing them into five groups: management, design, technology, policy, and infrastructure. Delphi analysis is used to examine the critical success factors for digital transformation identified in the literature and rate their importance during the preconstruction, construction, and facility management phases. Furthermore, this research results in the introduction of the Digital Transformation Level of Readiness Framework (DTRLF) to help facility management firms, clients, organizations, contractors, and designers comprehend the implementation of digital transformation within their respective domains and support decision-makers in establishing action to adapt related technologies in their respected project phases.
Ex Vivo Fluorescence Confocal Microscopy of MRI-Guided Targeted Prostate Biopsies for Rapid Detection of Clinically Significant Carcinomas—A Feasibility Study
Authors: Titze Ulf , Titze Barbara , Hansen Torsten , Barth Peter J. , Ali Furat Abd , Schneider Fried , Benndorf Matthias , Sievert Karl-Dietrich
Published: February 2024

Background: MRI-guided prostate biopsies from visible tumor-specific lesions (TBx) can be used to diagnose clinically significant carcinomas (csPCa) requiring treatment more selectively than conventional systematic biopsies (SBx). Ex vivo fluorescence confocal microscopy (FCM) is a novel technique that can be used to examine TBx prior to conventional histologic workup. Methods: TBx from 150 patients were examined with FCM on the day of collection. Preliminary findings were reported within 2 h of collection. The results were statistically compared with the final histology. Results: 27/40 (68%) of the csPCa were already recognized in the intraday FCM in accordance with the results of conventional histology. Even non-significant carcinomas (cisPCa) of the intermediate and high-risk groups (serum prostate-specific antigen (PSA) > 10 or 20 ng/mL) according to conventional risk stratifications were reliably detectable. In contrast, small foci of cisPCa were often not detected or were difficult to distinguish from reactive changes. Conclusion: The rapid reporting of preliminary FCM findings helps to reduce the psychological stress on patients, and can improve the clinical management of csPCa. Additional SBx can be avoided in individual cases, leading to lower rates of complications and scarring in the future surgical area. Additional staging examinations can be arranged without losing time. FCM represents a promising basis for future AI-based diagnostic algorithms.
Impact of Hypoxia on Radiation-Based Therapies for Liver Cancer
Authors: Villalobos Alexander , Lee Jean , Westergaard Sarah A. , Kokabi Nima
Published: February 2024

Background: Hypoxia, a state of low oxygen level within a tissue, is often present in primary and secondary liver tumors. At the molecular level, the tumor cells’ response to hypoxic stress induces proteomic and genomic changes which are largely regulated by proteins called hypoxia-induced factors (HIF). These proteins have been found to drive tumor progression and cause resistance to drug- and radiation-based therapies, ultimately contributing to a tumor’s poor prognosis. Several imaging modalities have been developed to visualize tissue hypoxia, providing insight into a tumor’s microbiology. Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane, and Google Scholar for all reports related to hypoxia on liver tumors. All relevant studies were summarized. Results: This review will focus on the impact of hypoxia on liver tumors and review PET-, MRI-, and SPECT-based imaging modalities that have been developed to predict and assess a tumor’s response to radiation therapy, with a focus on liver cancers. Conclusion: While there are numerous studies that have evaluated the impact of hypoxia on tumor outcomes, there remains a relative paucity of data evaluating and quantifying hypoxia within the liver. Novel and developing non-invasive imaging techniques able to provide functional and physiological information on tumor hypoxia within the liver may be able to assist in the treatment planning of primary and metastatic liver lesions.
Preclinical Characterization of the Anti-Leukemia Activity of the CD33/CD16a/NKG2D Immune-Modulating TriNKET® CC-96191
Authors: Lunn-Halbert Margaret C. , Laszlo George S. , Erraiss Sarah , Orr Mark T. , Jessup Heidi K. , Thomas Heather J. , Chan Henry , Jahromi Mahan A. , Lloyd Jonathan , Cheung Ann F. , Chang Gregory P. , Dichwalkar Tanmay , Fallon Daniel , Grinberg Asya , Rodríguez-Arbolí Eduardo , Lim Sheryl Y. T. , Kehret Allie R. , Huo Jenny , Cole Frances M. , Scharffenberger Samuel C. , Walter Roland B.
Published: February 2024

Increasing efforts are focusing on natural killer (NK) cell immunotherapies for AML. Here, we characterized CC-96191, a novel CD33/CD16a/NKG2D immune-modulating TriNKET®. CC-96191 simultaneously binds CD33, NKG2D, and CD16a, with NKG2D and CD16a co-engagement increasing the avidity for, and activation of, NK cells. CC-96191 was broadly active against human leukemia cells in a strictly CD33-dependent manner, with maximal efficacy requiring the co-engagement of CD16a and NKG2D. A frequent CD33 single nucleotide polymorphism, R69G, reduced CC-96191 potency but not maximal activity, likely because of reduced CD33 binding. Similarly, the potency, but not the maximal activity, of CC-96191 was reduced by high concentrations of soluble CD33; in contrast, the soluble form of the NKG2D ligand MICA did not impact activity. In the presence of CD33+ AML cells, CC-96191 activated NK cells but not T cells; while maximum anti-AML efficacy was similar, soluble cytokine levels were 10- to >100-fold lower than with a CD33/CD3 bispecific antibody. While CC-96191-mediated cytolysis was not affected by ABC transporter proteins, it was reduced by anti-apoptotic BCL-2 family proteins. Finally, in patient marrow specimens, CC-96191 eliminated AML cells but not normal monocytes, suggesting selectivity of TriNKET-induced cytotoxicity toward neoplastic cells. Together, these findings support the clinical exploration of CC-96191 as in NCT04789655.
Evaluation of the Prognostic Value of Pretherapeutic Magnetic Resonance Imaging in Predicting Soft Tissue Sarcoma Radiation Response: A Retrospective Study from a Large Institutional Sarcoma Imaging Database
Authors: Vogin Guillaume , Lepage Matthias , Salleron Julia , Cuenin Mathilde , Blum Alain , Gondim Teixeira Pedro Augusto
Published: February 2024

Background: RT-induced hyalinization/fibrosis was recently evidenced as a significant independent predictor for complete response to neoadjuvant radiotherapy (RT) and survival in patients with soft tissue sarcoma (STS). Purpose: Non-invasive predictive markers of histologic response after neoadjuvant RT of STS are expected. Materials and Methods: From May 2010 to April 2017, patients with a diagnosis of STS who underwent neoadjuvant RT for limb STS were retrieved from a single center prospective clinical imaging database. Tumor Apparent Diffusion Coefficients (ADC) and areas under the time-intensity perfusion curve (AUC) were compared with the histologic necrosis ratio, fibrosis, and cellularity in post-surgical specimens. Results: We retrieved 29 patients. The median ADC value was 134.3 × 10−3 mm2/s. ADC values positively correlated with the post-treatment tumor necrosis ratio (p = 0.013). Median ADC values were lower in patients with less than 50% necrosis and higher in those with more than 50% (120.3 × 10−3 mm2/s and 202.0 × 10−3 mm2/s, respectively (p = 0.020). ADC values higher than 161 × 10−3 mm2/s presented a 95% sensitivity and a 55% specificity for the identification of tumors with more than 50% tumor necrosis ratio. Tumor-to-muscle AUC ratios were associated with histologic fibrosis (p = 0.036). Conclusions: ADC and perfusion AUC correlated, respectively, with radiation-induced tumor necrosis and fibrosis.
Supplement Use and Increased Risks of Cancer: Unveiling the Other Side of the Coin
Authors: Jabbari Parnian , Yazdanpanah Omid , Benjamin David J. , Rezazadeh Kalebasty Arash
Published: February 2024

There is a rising trend in the consumption of dietary supplements, especially among adults, with the purpose of improving health. While marketing campaigns tout the potential health benefits of using dietary supplements, it is critical to evaluate the potential harmful effects associated with these supplements as well. The majority of the scarce research on the potential harmful effects of vitamins focuses on the acute or chronic toxicities associated with the use of dietary supplements. Quality research is still required to further investigate the risks of long-term use of dietary supplements, especially the risk of developing cancers. The present review concentrates on studies that have investigated the association between the risk of developing cancers and associated mortality with the risk of dietary supplements. Such an association has been reported for several vitamins, minerals, and other dietary supplements. Even though several of these studies come with their own shortcomings and critics, they must draw attention to further investigate long-term adverse effects of dietary supplements and advise consumers and healthcare providers to ponder the extensive use of dietary supplements.
Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy
Authors: Yim Hyung Joon , Kang Seong Hee , Jung Young Kul , Ahn Sang Hoon , Kim Won , Yang Jin Mo , Jang Jae Young , Kweon Yong Oh , Cho Yong Kyun , Kim Yoon Jun , Hong Gun Young , Kim Dong Joon , Sohn Joo Hyun , Lee Jin Woo , Park Sung Jae , Yim Sun Young , Park Jin Kyung , Um Soon Ho
Published: February 2024

No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806.
B1 Power Modification for Amide Proton Transfer Imaging in Parotid Glands: A Strategy for Image Quality Accommodation and Evaluation of Tumor Detection Feasibility
Authors: Wu Xiaoqian , Su Tong , Chen Yu , Xu Zhentan , Wang Xiaoqi , Hu Geli , Wang Yunting , Wong Lun M. , Zhang Zhuhua , Zhang Tao , Jin Zhengyu
Published: February 2024

Background: In the application of APTw protocols for evaluating tumors and parotid glands, inhomogeneity and hyperintensity artifacts have remained an obstacle. This study aimed to improve APTw imaging quality and evaluate the feasibility of difference B1 values to detect parotid tumors. Methods: A total of 31 patients received three APTw sequences to acquire 32 lesions and 30 parotid glands (one patient had lesions on both sides). Patients received T2WI and 3D turbo-spin-echo (TSE) APTw imaging on a 3.0 T scanner for three sequences (B1 = 2 μT, 1 μT, and 0.7 μT in APTw 1, 2, and 3, respectively). APTw image quality was evaluated using four-point Likert scales in terms of integrity and hyperintensity artifacts. Image quality was compared between the three sequences. An evaluable group and a trustable group were obtained for APTmean value comparison. Results: Tumors in both APT2 and APT3 had fewer hyperintensity artifacts than in APT1. With B1 values decreasing, tumors had less integrity in APTw imaging. APTmean values of tumors were higher than parotid glands in traditional APT1 sequence though not significant, while the APTmean subtraction value was significantly different. Conclusions: Applying a lower B1 value could remove hyperintensity but could also compromise its integrity. Combing different APTw sequences might increase the feasibility of tumor detection.
Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells’ Escape from the Bone Marrow Microenvironment
Authors: Verbruggen Stefaan W. , Freeman Ciara L. , Freeman Fiona E.
Published: February 2024

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments. To build upon these advances, it is crucial to develop models of MM evolution, particularly focusing on understanding the biological mechanisms behind its development outside the bone marrow. This comprehensive understanding is essential to devising innovative treatment strategies. This review emphasizes the role of 3D models, specifically addressing the bone marrow microenvironment and development of extramedullary sites. It explores the current state-of-the-art in MM modelling, highlighting challenges in replicating the disease’s complexity. Recognizing the unique demand for accurate models, the discussion underscores the potential impact of these advanced 3D models on understanding and combating this heterogeneous and still incurable disease.
Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy
Authors: Chang Pei-Hung , Chen Hung-Yi , Chang Yueh-Shih , Su Po-Jung , Huang Wen-Kuan , Lin Cheng-Feng , Hsieh Jason Chia-Hsun , Wu Chun-Te
Published: February 2024

This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%, p = 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months, p = 0.078) and OS (median, not reached vs. 26.8 months, p = 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.
Survival of Patients with Sinonasal Cancers in a Population-Based Registry, Lombardy, Italy, 2008–2023
Authors: Consonni Dario , Stella Simona , Denaro Nerina , Binazzi Alessandra , Dallari Barbara , Rugarli Sabrina , Borello Flavia , Coviello Enzo , Mensi Carolina
Published: February 2024

Sinonasal cancers (SNCs) are rare malignancies associated with occupational exposures. The aim of this study was to analyse the survival of SNC patients using data from the population-based SNC registry of the Lombardy region (10 million people), Italy. We included epithelial SNC cases registered in 2008–2020 and followed-up for vital status until 31 July 2023. Multivariate flexible parametric models with time-dependent covariates were fitted to calculate excess hazard ratios (EHRs) and 95% confidence intervals (CIs) of death. Based on 827 cases (553 males, 274 females) and 514 deaths (345 males, 169 females), the 5-year observed survival was 49% and the net survival was 57%. Age had a substantial impact on survival, particularly within the first year (EHR, 1.35; 95% CI, 1.12–1.51 per 10 years). Compared with the nasal cavity, the EHR for paranasal sinuses was 4.70 (95% CI, 2.96–7.47) soon after diagnosis. Compared with squamous cell carcinomas, the EHR was 0.69 (95% CI, 0.52–0.91) for adenocarcinomas, 1.68 (95% CI, 1.20–2.35) for undifferentiated and unspecified carcinomas, and 1.78 (95% CI, 1.07–2.95) for neuroendocrine carcinomas. Age and cancer site showed time-dependent effects on prognosis, especially within the first month after diagnosis. Prognosis was also markedly affected by cancer morphology. No associations were found for gender and period of diagnosis.
The Efficacy and Safety of Immune Checkpoint Inhibitors in Adrenocortical Carcinoma: A Systematic Review and Meta-Analysis
Authors: Ababneh Obada , Ghazou Alina , Alawajneh Mohmmad , Alhaj Mohammad Saleh , Bani-Hani Abdullah , Alrabadi Nasr , Shreenivas Aditya
Published: February 2024

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC) remains uncertain. Thus, we conducted a systematic review and meta-analysis to summarize the efficacy and tolerability of ICIs in patients with advanced ACC. We searched PubMed, Scopus, and CENTRAL for studies that used ICIs in ACC. Studies with more than five patients were included in the meta-analysis of the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and grade 3/4 adverse events. Twenty studies with 23 treatment arms and 250 patients were included. Single-agent anti-PD1 or anti-PD-L1 treatment was utilized in 13 treatment arms, whereas an anti-PD1 or anti-PD-L1 and anti-CTLA4 combination was used in 4 treatment arms. Other anti-PD1- or anti-PD-L1-based combinations were used in five treatment arms. The ORR was 14% (95% CI = 10–19%, I2 = 0%), and the DCR was 43% (95% CI = 37–50%, I2 = 13%). The combination anti-PD1- or anti-PD-L1-based treatment strategies did not correlate with higher responses compared with monotherapy. The median OS was 13.9 months (95% CI = 7.85–23.05), and the median PFS was 2.8 months (95% CI = 1.8–5.4). ICIs have a modest efficacy in advanced ACC but a good OS. Further studies are needed to investigate predictive biomarkers for ICI response and to compare ICI-based strategies with the current standard of care.
Ubiquitin B, Ubiquitin C, and β-Catenin as Promising Diagnostic and Prognostic Tools in Prostate Cancer
Authors: Piątkowska Daria , Klimaszewska-Wiśniewska Anna , Kosińska Alicja , Wujec Radosław , Grzanka Dariusz , Durślewicz Justyna
Published: February 2024

Prostate cancer (PC) is a major global public health concern, imposing a significant burden on men and ranking as the second most prevalent malignancy. This study delves into the intricate world of ubiquitination processes and expression regulation, with a specific focus on understanding the roles of ubiquitin B (UBB), ubiquitin C (UBC), and β-Catenin in PC development. We thoroughly analyze the expression profiles of UBB, UBC, and β-Catenin, investigating their interactions and associations with clinical and histopathological data. These findings offer valuable insights into their potential as robust prognostic markers and their significance for patient survival. Our research uncovers the upregulation of UBB and UBC expression in PC tissues, and an even more pronounced expression in lymph node metastases, highlighting their pivotal roles in PC progression. Moreover, we identify a compelling correlation between high UBB and UBC levels and diminished overall survival in PC patients, emphasizing their clinical relevance. Additionally, we observe a significant reduction in membranous β-Catenin expression in PC tissues. Importantly, abnormal β-Catenin expression is strongly associated with shorter survival in PC patients and serves as a significant, independent prognostic factor for patient outcomes. Kaplan–Meier survival analysis indicates that patients with tumors characterized by simultaneous UBB and aberrant β-Catenin expression exhibit the poorest overall survival. These collective insights underline the clinical importance of evaluating UBB, UBC, and β-Catenin as combined prognostic markers in PC.