bluuebunny/crossref_metadata_2025 huggingface dataset:
Color Standardization of Chemical Solution Images Using Template-Based Histogram Matching in Deep Learning Regression
Authors: Kwiek Patrycja , Jakubowska Małgorzata
Published: August 2024

Color distortion in an image presents a challenge for machine learning classification and regression when the input data consists of pictures. As a result, a new algorithm for color standardization of photos is proposed, forming the foundation for a deep neural network regression model. This approach utilizes a self-designed color template that was developed based on an initial series of studies and digital imaging. Using the equalized histogram of the R, G, B channels of the digital template and its photo, a color mapping strategy was computed. By applying this approach, the histograms were adjusted and the colors of photos taken with a smartphone were standardized. The proposed algorithm was developed for a series of images where the entire surface roughly maintained a uniform color and the differences in color between the photographs of individual objects were minor. This optimized approach was validated in the colorimetric determination procedure of vitamin C. The dataset for the deep neural network in the regression variant was formed from photos of samples under two separate lighting conditions. For the vitamin C concentration range from 0 to 87.72 µg·mL−1, the RMSE for the test set ranged between 0.75 and 1.95 µg·mL−1, in comparison to the non-standardized variant, where this indicator was at the level of 1.48–2.29 µg·mL−1. The consistency of the predicted concentration results with actual data, expressed as R2, ranged between 0.9956 and 0.9999 for each of the standardized variants. This approach allows for the removal of light reflections on the shiny surfaces of solutions, which is a common problem in liquid samples. This color-matching algorithm has universal character, and its scope of application is not limited.
Pitfalls in Metaheuristics Solving Stoichiometric-Based Optimization Models for Metabolic Networks
Authors: Briones-Báez Mónica Fabiola , Aguilera-Vázquez Luciano , Rangel-Valdez Nelson , Zuñiga Cristal , Martínez-Salazar Ana Lidia , Gomez-Santillan Claudia
Published: August 2024

Flux Balance Analysis (FBA) is a constraint-based method that is commonly used to guide metabolites through restricting pathways that often involve conditions such as anaplerotic cycles like Calvin, reversible or irreversible reactions, and nodes where metabolic pathways branch. The method can identify the best conditions for one course but fails when dealing with the pathways of multiple metabolites of interest. Recent studies on metabolism consider it more natural to optimize several metabolites simultaneously rather than just one; moreover, they point out the use of metaheuristics as an attractive alternative that extends FBA to tackle multiple objectives. However, the literature also warns that the use of such techniques must not be wild. Instead, it must be subject to careful fine-tuning and selection processes to achieve the desired results. This work analyses the impact on the quality of the pathways built using the NSGAII and MOEA/D algorithms and several novel optimization models; it conducts a study on two case studies, the pigment biosynthesis and the node in glutamate metabolism of the microalgae Chlorella vulgaris, under three culture conditions (autotrophic, heterotrophic, and mixotrophic) while optimizing for three metabolic intermediaries as independent objective functions simultaneously. The results show varying performances between NSGAII and MOEA/D, demonstrating that the selection of an optimization model can greatly affect predicted phenotypes.
Hyperspectral Python: HypPy
Authors: Bakker Wim , van Ruitenbeek Frank , van der Werff Harald , Hecker Christoph , Dijkstra Arjan , van der Meer Freek
Published: August 2024

This paper describes the design, implementation, and usage of a Python package called Hyperspectral Python (HypPy). Proprietary software for processing hyperspectral images is expensive, and tools developed using these packages cannot be freely distributed. The idea of HypPy is to be able to process hyperspectral images using free and open-source software. HypPy was developed using Python and relies on the array-processing capabilities of packages like NumPy and SciPy. HypPy was designed with practical imaging spectrometry in mind and has implemented a number of novel ideas. To name a few of these ideas, HypPy has BandMath and SpectralMath tools for processing images and spectra using Python statements, can process spectral libraries as if they were images, and can address bands by wavelength rather than band number. We expect HypPy to be beneficial for research, education, and projects using hyperspectral data because it is flexible and versatile.
A Frequency-Independent Phase Shifter
Authors: Csanád Máté , Val Baker Amira K. F. , Oomen Paul
Published: August 2024

In this paper, we utilise optimization methods to determine a frequency-independent phase shift such that two phase-shifted versions of a signal can be summed and the resulting amplitude spectrum is unchanged. A phase difference between two signals is thus defined, which remains constant for all frequencies within a given range. For the intended purpose of this study, we set the frequency range to the audible human hearing range of 16 Hz–20 kHz. We found that a new 3-stage filter method provides a variable phase shifter (i.e., ϕ = 0–360°) without the need for additional amplifiers. In addition, we present a new method that reduces the number of filters necessary, improving both the accuracy and efficiency of current techniques.
Integrated Design and Simulation of Helicopter Nuclear, Biological, and Chemical Protection System
Authors: Wen Yilong , Mao Xiaodong , Wang Hexiang , Pang Liping , Zhao Quanyu
Published: August 2024

The helicopter’s aircrew faces significant challenges in nuclear, biological, and chemical (NBC) environments due to limited protection devices and crowded space. To safeguard the security and ensure the comfort of the aircrew, the development of a helicopter NBC protection system is crucial. In this study, a helicopter NBC protection system was designed using a top-level architecture with an advanced system-integrated approach. Detailed configuration designs were developed for each subsystem, including air source pressurization, renewable NBC filtration ventilation, cabin temperature, and pressure control system. To verify the reliability of the adsorbent model, a Langmuir isotherm equation was adapted and validated using the experiment data. To verify the performance of the designed system, a dynamic simulation model was created using AMESIM. The findings demonstrate that the cabin temperature and pressure control system can greatly satisfy the demand for aircrews under various working conditions. Furthermore, the renewable NBC filtration ventilation system effectively adsorbs NBC substances and achieves onboard regeneration, thereby extending the working lifespan in contaminated environments. This study contributes to providing an innovative idea for helicopter NBC protection systems.
Ultrasound-Guided Interphalangeal Injection (US-IPI) of Mucoid Cysts as a Non-Surgical Option: Technical Notes and Clinical Efficacy
Authors: Faiella Eliodoro , Vergantino Elva , Santucci Domiziana , Bruno Amalia , Pacella Giuseppina , Panasiti Vincenzo , Beomonte Zobel Bruno , Grasso Rosario Francesco
Published: August 2024

Digital mucous cysts (DMCs) are common soft tissue tumors affecting interphalangeal joints. Various treatment options exist, with surgical excision being the standard. Ultrasound-guided cortisone (CC) injection into the distal interphalangeal (DIP) joint has been proposed as a therapeutic alternative. This study aims to assess the technical success and clinical efficacy of US-IPI in terms of swelling resolution and pain control. Fifty-two patients with DMCs underwent CCs DIP joint ultrasound-guided infiltration. Eighty-three percent of patients exhibited a positive response to US-IPI, with a significant reduction in NRS pain scores (p < 0.01). Persistent pain in 17% of patients was effectively managed with marked improvement after a secondary infiltration. Joint swelling was reduced in 68% of patients within 1 month, with complete resolution by 3 to 6 months. No recurrence was reported at the 6-month follow-up. Pain assessment using the Numeric Rating Scale and joint swelling evaluation were conducted at follow-ups of 2 weeks, 1, 3, and 6 months. Statistical analysis was performed to compare pre- and post-procedure NRS pain scores. Here, we show that US-IPI of DMCs is an effective therapeutic option that provides immediate pain relief and long-term aesthetic improvement, resulting in an alternative option to surgical excision.
A Retrospective Observational Study of Post-Induction Low Systolic Blood Pressure and Associated Patient and Perioperative Factors in Infants Undergoing General Anesthesia for Inguinal Hernia Repair
Authors: Nelson Olivia , Wu Lezhou , Berger Jessica A. , Yuan Ian , Padiyath Asif , Stricker Paul A. , Tsui Fuchiang Rich , Simpao Allan F.
Published: August 2024

Background: Infants are at risk of cerebral hypoperfusion from low blood pressure during anesthesia. We conducted a retrospective observational study to determine the patient and perioperative factors associated with low systolic blood pressure (SBP) in healthy infants. Methods: We obtained perioperative data of 266 infants aged 0–6 months who underwent inguinal hernia repair between January 2015 and March 2019 at our institution. SBP was analyzed during two phases: the preparation phase (20 min before procedure start until incision) and the surgical phase (15 to 35 min after procedure start). Low SBP was defined as a value lower than two standard deviations below the 50th percentile for a phase- and weight-specific reference value. Results: Low SBP was observed in 11% (29/265) and 5% (13/259) of patients during the preparation and surgical phases, respectively. Neuromuscular blockade use was associated with normal SBP in both phases (regression coefficient β = 6.15 and p = 0.002, regression coefficient β = 6.52 and p < 0.001, respectively). SBP was more strongly associated with weight than with age (ratio of adjusted standardized regression coefficient = 2.0 in both phases). After controlling for covariates, patients given neuromuscular blockade had significantly fewer low SBP measurements during the preparation phase (regression coefficient β = −1.99 and p < 0.001). Conclusions: With respect to patient factors, in healthy infants under general anesthesia, weight was more strongly associated with SBP than age. A neuromuscular blocking agent administered during anesthesia induction was associated with fewer low SBP measurements in the preparation phase.
Basic Circuit Model of Voltage Source Converters: Methodology and Modeling
Authors: Ndeke Christian Bipongo , Adonis Marco , Almaktoof Ali
Published: August 2024

Voltage source converters (VSCs) have emerged as the key components in modern power systems, facilitating efficient energy conversion and flexible power flow control. Understanding the fundamental circuit model of VSCs is essential for their accurate modeling and analysis in power system studies. A basic voltage source converter circuit model connected to an LC filter is essential because it lowers the harmonic distortions and enhances the overall power quality of the micro-grid. This guarantees a clean and steady power supply, which is necessary for the integration of multiple renewable energy sources and sensitive loads. A comprehensive methodology for developing a basic circuit model of VSCs, focusing on the key components and principals involved, is presented in this paper. The methodology includes the modeling of space vector pulse-width modulation (SVPWM) as well as the direct quadrature zero synchronous reference frame. Different design controls, including the design of current control loop in the S-domain, the design of the direct current (DC) bus voltage control loop in the S-domain, and the design of the alternating current (AC) voltage control loop in the S-domain, are explored to capture the dynamic behavior and control strategies of VSCs accurately. The proposed methodology provides a systematic framework for modeling VSCs, enabling engineers and researchers to analyze their performance and assess their impact on power system stability and operation. Future studies can be conducted by using case studies and simulation scenarios to show the efficiency and applicability of the developed models in analyzing VSC-based power electronics applications, including high-voltage direct current (HVDC) transmission systems and flexible alternating current transmission systems (FACTS). The significance of this work lies in its potential to advance the understanding and application of VSCs, contributing to more resilient and efficient power systems. By providing a solid foundation for future research and development, this study supports the ongoing integration of renewable energy sources and the advancement of modern electrical infrastructure.
Multi–Dimensional Data Analysis of Deep Language in J.R.R. Tolkien and C.S. Lewis Reveals Tight Mathematical Connections
Authors: Matricciani Emilio
Published: August 2024

Scholars of English Literature unanimously say that J.R.R. Tolkien influenced C.S. Lewis’s writings. For the first time, we have investigated this issue mathematically by using an original multi-dimensional analysis of linguistic parameters, based on surface deep language variables and linguistic channels. To set our investigation in the framework of English Literature, we have considered some novels written by earlier authors, such as C. Dickens, G. MacDonald and others. The deep language variables and the linguistic channels, discussed in the paper, are likely due to writers’ unconscious design and reveal connections between texts far beyond the writers’ awareness. In summary, the capacity of the extended short-term memory required to readers, the universal readability index of texts, the geometrical representation of texts and the fine tuning of linguistic channels within texts—all tools largely discussed in the paper—revealed strong connections between The Lord of the Rings (Tolkien), The Chronicles of Narnia, The Space Trilogy (Lewis) and novels by MacDonald, therefore agreeing with what the scholars of English Literature say.
A Longitudinal Study: Microbiological Quality of Raw Beef from Halal and Non-Halal Meat Markets in the United States
Authors: Al-Mahmood Omar A. , Jiang Xiuping , Bridges William C. , Fraser Angela M.
Published: August 2024

Halal means permissible according to Islamic law. Halal meat is obtained by hand slaughtering an animal that is not stunned and that is blessed by a Muslim individual immediately before slaughter. The purpose of this study was to determine the microbiological quality of raw meat from halal meat markets. A total of 138 beef samples were purchased from three halal (n = 72 samples) and three non-halal markets (n = 66 samples) between November 2016 and October 2017. All samples were analyzed for the presence of indicator organisms—aerobic plate counts (APCs), Enterobacteriaceae counts (ECs), total coliform counts (TCCs), and generic Escherichia coli (ECCs). The levels of APCs, ECs, TCCs, and ECCs (mean log CFU/g) in halal samples were 4.93 (100%), 2.89 (91.7%), 2.87 (94.4%), and 1.09 (18.1%), respectively, and those in non-halal samples were 4.92 (100%), 3.07 (95.5%), 3.02 (89.4%), and 1.15 (16.7%), respectively. The levels of TCCs and ECs were higher in halal samples during the summer compared to the other three seasons, whereas the highest ECCs in halal samples were found during autumn. In non-halal samples, significant differences were observed in the ECCs, TCCs, and ECs across seasons, with the highest level of contamination during autumn. Samples having higher levels of indicator organisms (APCs, ECs, TCCs, and ECCs) were more likely to be positive for pathogenic bacteria. The high levels of indicator organisms in both halal and non-halal retail meat samples suggest that the operation size, and not halal or non-halal meat classification, is associated with the microbiological quality. These findings can inform food safety interventions targeting small meat markets in the United States.
Therapeutic Architecture and Temporality: Evidence-Based Design for Long-Stay Facilities for Individuals with Severe Intellectual Disabilities and Challenging Behaviour
Authors: Vollmer Tanja C. , Koppen Gemma , Iovița Claudia , Schießl Lara
Published: August 2024

Since individuals with severe and profound Intellectual Disabilities (IDs) have no concept of time, it is difficult for them to autonomously maintain daily structures. Those affected are dependent throughout their lives on external care structures. Even though research suggests that individuals with IDs should live in smaller facilities, individuals with higher support needs are more likely to be placed in large institutions and clustered group homes. The aim of this study was to define design criteria and test their applicability to a residential building design whose architecture enables individuals with IDs to develop autonomy through spatially experienced temporality. Qualitative data was collected in a mixed method evidence-based design approach: systematic behavioural observations, structured interviews, focus groups, and the UV-index method. Four design criteria could be described that contribute to an autonomy-promoting temporality: (a) spatial sequencing and repetition, (b) privacy-related variation of spatial dimensions, (c) spatial orchestration of daylight, and (d) constant emotional proximity to the caregiver. The hypothesis of using architecture to promote temporality in clients with IDs and Challenging Behaviour (CB) has proven to be potentially effective in designing a therapeutic environment. Our findings provide valuable data on how long-stay facilities should be designed in the future.
Optimizing Unmanned Air–Ground Vehicle Maneuvers Using Nonlinear Model Predictive Control and Moving Horizon Estimation
Authors: Morando Alessandra Elisa Sindi , Bozzi Alessandro , Graffione Simone , Sacile Roberto , Zero Enrico
Published: August 2024

In this paper, Nonlinear Model Predictive Control (NMPC) and Nonlinear Moving Horizon Estimator (NMHE) are combined to control, in a distributed way, a heterogeneous fleet composed of a steering car and a quadcopter. In particular, the ground vehicle in the role of the leader communicates its one-step future position to the drone, which keeps the formation along the desired trajectory. Inequality constraints are introduced in a switching control fashion to the leader’s NMPC formulation to avoid obstacles. In the literature, few works using NMPC and NMHE deal with these two vehicles together. Moreover, the presented scheme can tackle noisy, partial, and missing measurements of the agents’ state. Results show that the ground car can avoid detected obstacles, keeping the tracking errors of both robots in the order of a few centimeters, thanks to trustworthy NMHE estimates and NMPC predictions.
Cost Function Approach for Dynamical Component Analysis: Full Recovery of Mixing and State Matrix
Authors: Hüper Knut , Schlarb Markus , Uhl Christian
Published: August 2024

A reformulation of the dynamical component analysis (DyCA) via an optimization-free approach is presented. The original cost function approach is converted into a numerical linear algebra problem, i.e., the computation of coupled singular-value decompositions. A simple algorithm is presented together with numerical experiments to document the feasability of the approach. This methodology is able to recover the mixing and state matrices of multivariate signals from high-dimensional measured data fully.
Cloud Point Extraction in Beverage Analysis: Innovations and Applications for Trace Elements
Authors: Hagarová Ingrid , Urík Martin
Published: August 2024

Cloud point extraction (CPE) has emerged as a highly promising method for the isolation and preconcentration of trace elements from beverages. By utilizing nonionic surfactants to form micellar structures that encapsulate analytes, CPE significantly enhances extraction efficiency and detection limits, often achieving improvements by several orders of magnitude. The optimization of CPE conditions, particularly the selection of surfactants and complexing agents, plays a crucial role in ensuring accurate analytical results. This review underscores the integration of CPE with spectrometric methods as a powerful approach for the separation, preconcentration, and quantification of numerous (ultra)trace elements across a wide range of beverages, including drinking water, wine, beer, juices, tea, and milk. The analytical potential of this integration is substantiated by the comprehensive examples listed in this paper, which include various strategies for sample preparation tailored specifically for different beverage types. While highlighting the effectiveness of conventional CPE methods, this review also emphasizes recent modifications and advancements in CPE techniques that further enhance their utility in beverage analysis. These advancements not only improve detection sensitivity but also align with the principles of green chemistry by reducing solvent consumption and energy requirements.
Verification and Validation of Advanced Control Systems for a Spinal Joint Wear Simulator
Authors: Iyer Kaushikk Ravender , Keeling David , Hall Richard M.
Published: August 2024

Wear simulation aims to assess wear rates and their dependence on factors like load, kinematics, temperature, and implant orientation. Despite its significance, there is a notable gap in research concerning advancements in simulator control systems and the testing of clinically relevant waveforms. This study addresses this gap by focusing on enhancing the conventional proportional–integral–derivative (PID) controller used in joint simulators through the development of a fuzzy logic-based controller. Leveraging a single-input multiple-output (SIMO) fuzzy logic control system, this study aimed to improve displacement control, augmenting the traditional proportional–integral (PI) tuning approach. The implementation and evaluation of a novel Fuzzy-PI control algorithm were conducted on the Leeds spine wear simulator. This study also included the testing of dailyliving (DL) profiles, particularly from the hip joint, to broaden the scope of simulation scenarios. While both the conventional PI controller and the Fuzzy-PI controller met ISO tolerance criteria for the spine flexion–extension (FE) profile at 1 Hz, the Fuzzy-PI controller demonstrated superior performance at higher frequencies and with DL profiles due to its real-time adaptive tuning capability. The Fuzzy-PI controller represents a significant advancement in joint wear simulation, offering improved control functionalities and more accurate emulation of real-world physiological dynamics.
Exploring Cognitive Impairments Associated with Primary Open-Angle Glaucoma and Exfoliation Glaucoma
Authors: Kadoh Yoichi , Kubota Suguru , Shimomine Soichiro , Tanito Masaki
Published: August 2024

This study explored the link between different types of glaucoma and cognitive function in a cohort of 620 Japanese patients. Participants were categorized into primary open-angle glaucoma (PG), exfoliation glaucoma (EG), and non-glaucomatous control groups. The findings revealed a significant decline in cognitive function as indicated by the Mini-Cog test in the EG group (mean ± SD: 4.0 ± 1, 95% CI: 3.9 to 4.2) compared to the PG group (4.4 ± 0.1, 4.3 to 4.5, p < 0.0001). Levels of fingertip measured advanced glycation end-products (AGEs) were significantly higher in the EG group (mean ± SD: 0.45 ± 0.006, 95% CI: 0.44 to 0.46) compared to the PG group (0.43 ± 0.004, 0.42 to 0.44, p = 0.0014). Although the multivariate analysis initially showed no direct association between glaucoma types and Mini-Cog scores, the EG group exhibited higher age and intraocular pressure (IOP) compared to the PG group. Further analysis revealed that high levels of AGEs were associated with cognitive decline and decreased mean visual fields in the EG group. Age was identified as a cofounding factor in these associations. An inverse correlation was observed between the accumulation of AGEs and skin carotenoid levels. Early detection of cognitive decline in glaucoma patients could enable timely intervention to preserve visual fields. Fingertip measurements of skin carotenoids and AGEs offer promising potential as non-invasive, straightforward diagnostic tools that could be widely adopted for monitoring ophthalmic and cognitive health in glaucoma patients.
Mitral Transcatheter Edge-to-Edge Repair and Clinical Value of Novel Echocardiographic Biomarkers: A Hypothesis-Generating Study
Authors: Solsona-Caravaca Javier , Fernández-Galera Rubén , González-Fernández Víctor , Airale Lorenzo , Rivas Johny , Scudeler Luca , Vallejo Núria , Teixidó-Turà Gisela , Casas Guillem , Valente Filipa , Oliveró Ruper , Belahnech Yassin , Martí Gerard , García Bruno , Ferreira-González Ignacio , Rodríguez-Palomares José F. , Galian-Gay Laura
Published: August 2024

Background: Longitudinal data on reverse cardiac remodeling and outcomes after transcatheter edge-to-edge repair (TEER) are limited. Methods: A total of 78 patients with severe mitral regurgitation (MR) were included retrospectively. All patients had echocardiography at baseline and again six months after TEER. They were monitored for a primary composite endpoint, consisting of heart failure hospitalization and cardiovascular death, over 13 months. Results: Significant decreases in the left ventricular ejection fraction (LVEF), all myocardial work indices (except global wasted work), and the left atrial reservoir were observed after TEER. Additionally, there was a decrease in the pulmonary artery systolic pressure and an increase in the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. A post-TEER TAPSE/PASP ratio of <0.47 (HR: 4.76, p-value = 0.039), and a post-TEER left atrial reservoir of <9.0% (HR: 2.77, p-value = 0.047) were associated with the primary endpoint. Conclusions: Echocardiography post-TEER reflects impairment in ventricular performance due to preload reduction and right ventricle and pulmonary artery coupling improvement. Short-term echocardiography after TEER identifies high-risk patients who could benefit from a close clinical follow-up. The prognostic significance of LA strain and the TAPSE/PASP ratio should be validated in subsequent large-scale prospective studies.
Ceftriaxone Inhibits Conditioned Fear and Compulsive-like Repetitive Marble Digging without Central Nervous System Side Effects Typical of Diazepam—A Study on DBA2/J Mice and a High-5HT Subline of Wistar–Zagreb 5HT Rats
Authors: Poljak Ljiljana , Miše Branko , Čičin-Šain Lipa , Tvrdeić Ante
Published: August 2024

Background: Ceftriaxone upregulates GLT1 glutamate transporter in the brain and may have anti-CFC and anti-OCD effects. Methods: Twenty WZ-5HT rats were used to investigate the effects of ceftriaxone on obsessive–compulsive (OCD)-like behaviour in the marble-burying (MB) test, freezing behaviour in contextual fear conditioning (CFC) and expression of GLT1 protein in the hippocampus or amygdala using immunoblots. Fifteen DBA/2J mice were used in the MB test. We also compared diazepam with ceftriaxone in open-field, beam-walking, and wire-hanging tests on 47 DBA/2J mice. Ceftriaxone (200 mg/kg) and saline were applied intraperitoneally, once daily for 7 (rats) or 5 (mice) consecutive days. A single dose of diazepam (1.5–3.0 mg/kg) or saline was injected 30 min before the behavioural tests. Results: Ceftriaxone significantly diminished OCD-like behaviour (↓ number of marbles buried) and freezing behaviour in CFC context session (↑ latencies, ↓ total duration, ↓ duration over four 2 min periods of the session) but increased GLT1 protein expression in the amygdala and hippocampus of rats. Diazepam induced sedation, ataxia and myorelaxation in mice. Ceftriaxone did not have these side effects. Conclusions: The results of this study confirm the anti-CFC and anti-OCD effects of ceftriaxone, which did not produce the unwanted effects typical of diazepam.
Cell-Based Treatment in Acute Myeloid Leukemia Relapsed after Allogeneic Stem Cell Transplantation
Authors: Canichella Martina , de Fabritiis Paolo
Published: August 2024

Allogeneic stem cell transplant (ASCT) remains the only treatment option for patients with high-risk acute myeloid leukemia (AML). Recurrence of leukemic cells after ASCT represents a dramatic event associated with a dismal outcome, with a 2-year survival rate of around 20%. Adoptive cell therapy (ACT) is a form of cell-based strategy that has emerged as an effective therapy to treat and prevent post-ASCT recurrence. Lymphocytes are the principal cells used in this therapy and can be derived from a hematopoietic stem cell donor, the patient themselves, or healthy donors, after being engineered to express the chimeric antigen receptor (CAR-T and UniCAR-T). In this review, we discuss recent advances in the established strategy of donor lymphocyte infusion (DLI) and the progress and challenges of CAR-T cells.
Perspectives on CRISPR Genome Editing to Prevent Prion Diseases in High-Risk Individuals
Authors: Medd Milan M. , Cao Qi
Published: August 2024

Prion diseases are neurodegenerative disorders caused by misfolded prion proteins. Although rare, the said diseases are always fatal; they commonly cause death within months of developing clinical symptoms, and their diagnosis is exceptionally difficult pre-mortem. There are no known cures or treatments other than symptomatic care. Given the aggressiveness of prion diseases on onset, therapies after disease onset could be challenging. Prevention to reduce the incidence or to delay the disease onset has been suggested to be a more feasible approach. In this perspective article, we summarize our current understandings of the origin, risk factors, and clinical manifestations of prion diseases. We propose a PCR testing of the blood to identify PRNP gene polymorphisms at codons 129 and 127 in individuals with familial PRNP mutations to assess the risk. We further present the CRISPR/Cas9 gene editing strategy as a perspective preventative approach for these high-risk individuals to induce a polymorphic change at codon 127 of the PRNP gene, granting immunity to prion diseases in selected high-risk individuals, in particular, in individuals with familial PRNP mutations.
The Role of Sodium Fluoride Mouthwash in Regulating FGF-2 and TGF-β Expression in Human Gingival Fibroblasts
Authors: Kato Nobue , Nakai Kumiko , Tanaka Hideki , Fukuzawa Kyoko , Hayashi Minii , Aoki Mikio , Kawato Takayuki
Published: August 2024

Sodium fluoride (NaF) is a fluoride application recommended by the World Health Organization for its efficacy and safety in preventing dental caries. Gingival fibroblasts that constitute the majority of connective tissue cells play a major role in wound healing via the expression of growth factors, including fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-β). This study examined the effect of NaF mouthwash on FGF-2 and TGF-β expression in human gingival fibroblasts (HGnFs). Fibroblasts were exposed to a medium with 225 ppmF NaF for 1 min, then switched to either 15 ppmF NaF for continuous stimulation or no NaF for transient stimulation. Continuous NaF stimulation significantly increased the gene and protein expression of FGF-2 and TGF-β in HGnFs compared to controls, suggesting NaF’s potential role in modulating periodontal tissue wound healing. Signaling pathway investigations showed the involvement of heterotrimeric GTP-binding proteins, calcium/calmodulin-dependent kinase II (CaMKII), and extracellular signal-regulated kinase (ERK) phosphorylation. Inhibiting CaMKII reduced NaF-induced FGF-2 and TGF-β expression, while ERK phosphorylation increased after NaF stimulation. These results highlight NaF mouthwash’s potential in promoting wound healing in extraction sockets, particularly during the mixed dentition period. Understanding NaF’s effects is clinically relevant due to the common use of fluoride products.
De-Escalation Strategies in HPV-Associated Oropharynx Cancer: A Historical Perspective with Future Direction
Authors: Wu Clinton , Kuzmin Paulina , Julian Ricklie
Published: August 2024

The incidence of HPV-related oropharyngeal cancers has increased in recent decades. While cure rates exceed those of HPV-negative head and neck cancers, both acute and long-term sequelae of chemotherapy, radiation and surgery have led to clinical investigation into de-escalation of treatment. De-escalation trials have sought to reduce long-term treatment-related morbidity by altering or omitting chemotherapy, reducing radiation, or incorporating less invasive surgical resection through transoral surgery. More recent approaches include the use of novel agents such as immunotherapy in place of cisplatin. With the advent of tumor-tissue-modified HPV DNA detection and monitoring in blood, new strategies incorporating this biomarker are being developed.
Proton Pencil Beam Scanning Facilitates the Safe Treatment of Extended Radiation Targets for Hodgkin Lymphoma: A Report from the Proton Collaborative Group Registry
Authors: Ebadi Maryam , Pankuch Mark , Boyer Sean , Chang John , Stevens Craig , Hall Matthew D. , Hasan Shaakir , Bates James E. , Flampouri Stella , Kole Adam J. , Mohindra Pranshu , Rossi Carl , Sanghvi Parag , McGee Lisa , Rana Zaker , Tseng Yolanda D.
Published: August 2024

Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT.
Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release
Authors: Harrer Dennis Christoph , Eder Matthias , Barden Markus , Pan Hong , Herr Wolfgang , Abken Hinrich
Published: August 2024

Chimeric antigen receptor (CAR) T cell therapy has achieved extraordinary success in eliminating B cell malignancies; however, so far, it has shown limited efficacy in the treatment of solid tumors, which is thought to be due to insufficient CAR T cell activation. We hypothesized that the transcription factor PU.1, a master regulator of innate cell functionality, may augment pro-inflammatory CAR T cell activation. T cells were engineered with a CEA-specific CAR together with the constitutive expression of PU.1. CAR-redirected T cell activation was recorded for canonical functionality in vitro under conditions of prolonged repetitive antigen exposure. Ectopic PU.1 expression in CAR T cells upregulated the costimulatory receptors CD40, CD80, CD86, and CD70, which, unexpectedly, did not augment effector functions but hampered the upregulation of 4-1BB, decreased IL-2 production, reduced CAR T cell proliferation, and impaired their cytotoxic capacities. Under “stress” conditions of repetitive engagement of cognate tumor cells, CAR T cells with ectopic PU.1 showed reduced persistence, and finally failed to control the growth of cancer cells. Mechanistically, PU.1 caused CAR T cells to secrete IFN-β, a cytokine known to promote CAR T cell attrition and apoptosis. Collectively, PU.1 can polarize the functional capacities of CAR T cells towards innate cells.
Diagnosis of Sarcopenia and Myosteatosis by Computed Tomography in Patients with Esophagogastric and Pancreatic Cancer
Authors: Sales-Balaguer Nerea , Sorribes-Carreras Patricia , Morillo Macias Virginia
Published: August 2024

The increase in the global incidence of cancer highlights the need to continue advancing in the techniques of diagnosis and nutritional assessment of cancer patients, given the prognostic and therapeutic impact of nutritional status. In this study, sarcopenia was evaluated as an independent predictor of morbidity and mortality. Data from 45 patients diagnosed with esophagogastric or pancreatic cancer were analyzed. Body composition was determined using computed tomography images, and functionality tests were performed. Sarcopenia was present in 22.2% of the patients, while only 31.1% had correct musculature. A reduction in muscle mass or function was observed in 46.7% of the patients. Likewise, the prevalence of myosteatosis reached 60% of the patients. No significant differences were found with regard to the presence of sarcopenia according to BMI classifications, so it is necessary to evaluate the patient with body composition techniques that include the evaluation of the different muscle and fat compartments. In conclusion, a comprehensive intervention is necessary to improve the detection of sarcopenia/myosteatosis and, in the future, to be able to carry out an approach that improves the quality of life and survival rates of patients.
Serum CD133-Associated Proteins Identified by Machine Learning Are Connected to Neural Development, Cancer Pathways, and 12-Month Survival in Glioblastoma
Authors: Joyce Thomas , Tasci Erdal , Jagasia Sarisha , Shephard Jason , Chappidi Shreya , Zhuge Ying , Zhang Longze , Cooley Zgela Theresa , Sproull Mary , Mackey Megan , Camphausen Kevin , Krauze Andra V.
Published: August 2024

Glioma is the most prevalent type of primary central nervous system cancer, while glioblastoma (GBM) is its most aggressive variant, with a median survival of only 15 months when treated with maximal surgical resection followed by chemoradiation therapy (CRT). CD133 is a potentially significant GBM biomarker. However, current clinical biomarker studies rely on invasive tissue samples. These make prolonged data acquisition impossible, resulting in increased interest in the use of liquid biopsies. Our study, analyzed 7289 serum proteins from 109 patients with pathology-proven GBM obtained prior to CRT using the aptamer-based SOMAScan® proteomic assay technology. We developed a novel methodology that identified 24 proteins linked to both serum CD133 and 12-month overall survival (OS) through a multi-step machine learning (ML) analysis. These identified proteins were subsequently subjected to survival and clustering evaluations, categorizing patients into five risk groups that accurately predicted 12-month OS based on their protein profiles. Most of these proteins are involved in brain function, neural development, and/or cancer biology signaling, highlighting their significance and potential predictive value. Identifying these proteins provides a valuable foundation for future serum investigations as validation of clinically applicable GBM biomarkers can unlock immense potential for diagnostics and treatment monitoring.
Five-Year Relative Survival Rates of Women Diagnosed with Uterine Cancer by County-Level Socioeconomic Status Overall and across Histology and Race/Ethnicity
Authors: Wijayabahu Akemi T. , McGee-Avila Jennifer K. , Shiels Meredith S. , Harsono Alfonsus Adrian H. , Arend Rebecca C. , Clarke Megan A.
Published: August 2024

Understanding socioeconomic factors contributing to uterine cancer survival disparities is crucial, especially given the increasing incidence of uterine cancer, which disproportionately impacts racial/ethnic groups. We investigated the impact of county-level socioeconomic factors on five-year survival rates of uterine cancer overall and by histology across race/ethnicity. We included 333,013 women aged ≥ 30 years with microscopically confirmed uterine cancers (2000–2018) from the Surveillance, Epidemiology, and End Results 22 database followed through 2019. Age-standardized five-year relative survival rates were compared within race/ethnicity and histology, examining the differences across tertiles of county-level percent (%) <high-school education, %<150 percent poverty, %unemployment, median household income, and %urbanicity. Overall age-adjusted five-year relative survival was 77.7%. Rates were lowest among those residing in the least advantaged counties (tertile 3) and highest among the most advantaged (tertile 1): education (74.7% vs. 80.2%), poverty (72.9% vs. 79.8%), unemployment (75.7% vs. 80.5%), and income (73.3% tertile 1 vs. 78.1% tertile 3). Impact of county-level socioeconomic characteristics on survival across histology was minimal. We observed considerable survival disparities among NH-Black and NH-Native American/Alaskan Native women, regardless of tumor and socioeconomic characteristics. These findings add to our understanding of how county-level socioeconomic characteristics affect uterine cancer survival inequalities among racial/ethnic groups.
Senolytics and Senomorphics Targeting p38MAPK/NF-κB Pathway Protect Endothelial Cells from Oxidative Stress-Mediated Premature Senescence
Authors: Ya Jingyuan , Bayraktutan Ulvi
Published: August 2024

Oxidative stress is a prominent causal factor in the premature senescence of microvascular endothelial cells and the ensuing blood–brain barrier (BBB) dysfunction. Through the exposure of an in vitro model of human BBB, composed of brain microvascular endothelial cells (BMECs), astrocytes, and pericytes to H2O2, this study examined whether a specific targeting of the p38MAPK/NF-κB pathway and/or senescent cells could delay oxidative stress-mediated EC senescence and protect the BBB. Enlarged BMECs, displaying higher β-galactosidase activity, γH2AX staining, p16 expression, and impaired tubulogenic capacity, were regarded as senescent. The BBB established with senescent BMECs had reduced transendothelial electrical resistance and increased paracellular flux, which are markers of BBB integrity and function, respectively. Premature senescence disrupted plasma-membrane localization of the tight junction protein, zonula occludens-1, and elevated basement membrane-degrading matrix metalloproteinase-2 activity and pro-inflammatory cytokine release. Inhibition of p38MAPK by BIRB796 and NF-κB by QNZ and the elimination of senescent cells by a combination of dasatinib and quercetin attenuated the effects of H2O2 on senescence markers; suppressed release of the pro-inflammatory cytokines interleukin-8, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1; restored tight junctional unity; and improved BBB function. In conclusion, therapeutic approaches that mitigate p38MAPK/NF-κB activity and senescent cell accumulation in the cerebrovasculature may successfully protect BBB from oxidative stress-induced BBB dysfunction.
Sulfation of Various Polysaccharide Structures: Different Methods and Perspectives
Authors: Berezhnaya Yaroslava D. , Kazachenko Aleksandr S. , Kazachenko Anna S. , Malyar Yuriy N. , Borovkova Valentina S.
Published: August 2024

Sulfated polysaccharides have a variety of important biologically active properties, such as anticoagulant, hypolipidemic, antiviral activity, the ability to be a means of targeted drug delivery and to improve the water solubility of certain drugs. Initial and sulfated polysaccharides’ biological activity depends on the method of their preparation, composition and structure. Currently, there is an extensive body of literature data on methods for the sulfation of various natural polysaccharides. However, modern reviews on this topic mainly focus on the biological activity and application of sulfated polymers, rather than on synthesis methods. The latest comprehensive review on methods for the synthesis of sulfated polysaccharides was performed by Caputo in 2019. To further study this area, you need to know the latest trends in this topic. Based on this, we decided to create a new, up-to-date review covering most of the existing methods for the synthesis of sulfated polysaccharides. This work examined methods for the synthesis of biologically active polysaccharide sulfates and their effect on polymer characteristics, as well as the advantages and disadvantages of each method. Traditional methods for sulfating polysaccharides were reviewed such as using a complex of sulfur trioxide with pyridine, and new methods based on the use of toxic free and corrosive free reagents. Some data on the biological activity of the obtained polysaccharides are considered.
Lactone-Terminated Self-Assembled Monolayers for Mimicking Nanoscale Polyester Surfaces
Authors: Tajalli Pooria , Hernandez Rivera Jennifer M. , Omidiyan Mina , Lee Jong Moon , Tran Hung-Vu , Lee T. Randall
Published: August 2024

Two series of lactone-terminated alkanethiol adsorbates with five- and six-membered lactone groups, γ-COCnSH and δ-COCnSH (n = 11, 12), were synthesized and employed to create nanoscale self-assembled monolayers (SAMs) on gold substrates to mimic the properties of commercially available poly(lactic-co-glycolic acid) (PLGA) and poly(glycolic acid) (PGA) surfaces. 1H and 13C nuclear magnetic resonance (NMR) were employed to characterize the adsorbate molecules. The thicknesses of the corresponding self-assembled monolayers (SAMs) were evaluated by ellipsometry. The conformational characteristics of the SAMs were analyzed using polarization modulation infrared reflection adsorption spectroscopy (PM-IRRAS), with a focus on the C-H antisymmetric stretching vibrations of the alkyl spacers. To evaluate the packing densities of the monolayers, X-ray photoelectron spectroscopy (XPS) measurements were performed. Separately, contact angle measurements provided insights into the wettability of the surfaces. Remarkably, the contact angle data across a broad range of probe liquids for the γ-COC11SH and γ-COC12SH SAMs were consistently similar to each other and to the contact angle values of the PLGA surface, rather than to PGA. This finding suggests that the lactone-terminated SAMs investigated in this study effectively mimic nanoscale polyester surfaces, enabling the exploration of interfacial properties of polyesters in the absence of swelling and/or surface reconstruction phenomena.