bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering 3D-Printed Advanced Healthcare Materials for Periprosthetic Joint Infections
Authors: Yuste Iván , Luciano Francis C. , Anaya Brayan J. , Sanz-Ruiz Pablo , Ribed-Sánchez Almudena , González-Burgos Elena , Serrano Dolores R.
Published: July 2023

The use of additive manufacturing or 3D printing in biomedicine has experienced fast growth in the last few years, becoming a promising tool in pharmaceutical development and manufacturing, especially in parenteral formulations and implantable drug delivery systems (IDDSs). Periprosthetic joint infections (PJIs) are a common complication in arthroplasties, with a prevalence of over 4%. There is still no treatment that fully covers the need for preventing and treating biofilm formation. However, 3D printing plays a major role in the development of novel therapies for PJIs. This review will provide a deep understanding of the different approaches based on 3D-printing techniques for the current management and prophylaxis of PJIs. The two main strategies are focused on IDDSs that are loaded or coated with antimicrobials, commonly in combination with bone regeneration agents and 3D-printed orthopedic implants with modified surfaces and antimicrobial properties. The wide variety of printing methods and materials have allowed for the manufacture of IDDSs that are perfectly adjusted to patients’ physiognomy, with different drug release profiles, geometries, and inner and outer architectures, and are fully individualized, targeting specific pathogens. Although these novel treatments are demonstrating promising results, in vivo studies and clinical trials are required for their translation from the bench to the market.
Enterococcus hirae Mitral Valve Infectious Endocarditis: A Case Report and Review of the Literature
Authors: Gaudiano Roberta , Trizzino Marcello , Torre Salvatore , Virruso Roberta , Fiorino Fabio , Argano Vincenzo , Cascio Antonio
Published: July 2023

Enterococcus hirae is a rare pathogen in human infections, although its incidence may be underestimated due to its difficult isolation. We describe the first known case of E. hirae infective endocarditis (IE), which involves the mitral valve alone, and the seventh E. hirae IE worldwide. Case presentation: a 62-year-old male was admitted to our department with a five-month history of intermittent fever without responding to antibiotic treatment. His medical history included mitral valve prolapse, recent pleurisy, and lumbar epidural steroid injections due to lumbar degenerative disc disease. Pre-admission transesophageal echocardiography (TEE) showed mitral valve vegetation, and Enterococcus faecium was isolated on blood cultures by MALDI-TOF VITEK MS. During hospitalization, intravenous (IV) therapy with ampicillin and ceftriaxone was initiated, and E. hirae was identified by MALDI-TOF Bruker Biotyper on three blood culture sets. A second TEE revealed mitral valve regurgitation, which worsened due to infection progression. The patient underwent mitral valve replacement with a bioprosthetic valve and had an uncomplicated postoperative course; he was discharged after six weeks of IV ampicillin and ceftriaxone treatment.
Adaptive Parameter Estimation of the Generalized Extreme Value Distribution Using Artificial Neural Network Approach
Authors: Phoophiwfa Tossapol , Laosuwan Teerawong , Volodin Andrei , Papukdee Nipada , Suraphee Sujitta , Busababodhin Piyapatr
Published: July 2023

Parameter estimation strategies have long been a focal point in research due to their significant implications for understanding data behavior, including the dynamics of big data. This study offers an advancement in these strategies by proposing an adaptive parameter estimation approach for the Generalized Extreme Value distribution (GEVD) using an artificial neural network (ANN). Through the proposed adaptive parameter estimation approach, based on ANNs, this study addresses the parameter estimation challenges associated with the GEVD. By harnessing the power of ANNs, the proposed methodology provides an innovative and effective solution for estimating the parameters of the GEVD, enhancing our understanding of extreme value analysis. To predict the flood risk areas in the Chi river watershed in Thailand, we first determine the variables that are significant in estimation of the three GEVD parameters μ,σ, and ξ by considering the respective correlation coefficient and then estimating these parameters. The data were compiled from satellite and meteorological data in the Chi watershed gathered from the Meteorological Department and 92 meteorological stations from 2010 to 2021, and consist of such variables as the Normalized Difference Vegetation Index (NDVI), climate, rainfall, runoff, and so on. The parameter estimation focuses on the GEVD. Taking into consideration that the processes could be stationary (parameters are constant over time, S) or non-stationary (parameters change over time, NS), maximum likelihood estimation and ANN approaches are applied, respectively. Both cases are modeled with the GEVD for the monthly maximum rainfall. The Nash-Sutcliffe coefficient (NSE), is used to compare the performance and accuracy of the models. The results illustrate that the non-stationary model was suitable for 82 stations, while the stationary model was suitable for only 10 stations. The NSE values in each model range from 0.6 to 0.9. This indicated that all 92 models were highly accurate. Furthermore, it is found that meteorological variables, geographical coordinates, and NDVI, that are correlated with the shape parameter in the ANN model, are more significant than others. Finally, two-dimensional maps of the return levels in the 2, 5, 10, 20, 50, and 100-year return periods are presented for further application. Overall, this study contributes to the advancement of parameter estimation strategies in the context of extreme value analysis and offers practical implications for water resource management and flood risk mitigation.
Boosting the Performance of Lithium Metal Anodes with Three-Dimensional Lithium Hosts: Recent Progress and Future Perspectives
Authors: Chen Lina , Liu Haipeng , Li Mengrui , Zhou Shiqiang , Mo Funian , Yu Suzhu , Wei Jun
Published: July 2023

Li metal has emerged as a promising anode material for high energy density batteries, due to its low electrochemical potential and high specific capacity of 3860 mAh·g−1. These characteristics make it an attractive choice for electric vehicles and power grids. However, Li-metal batteries are plagued by dendrite issues stemming from the high reactivity of Li metal, which can ultimately result in battery failure or even safety concerns. To overcome this challenge, various strategies have been proposed to prevent dendrite formation and enhance the safety of Li-metal batteries. This review critically examines the recent progress in the development of dendrite-free Li-metal batteries, with a particular emphasis on advanced approaches of 3D Li metal host construction. Our goal is to provide a comprehensive overview of the 3D hosts for suppressing Li dendrites and to offer guidance for the future development of superior Li metal batteries.
Outcomes Using Focused Shockwave for Treatment of Bone Stress Injury in Runners
Authors: Beling Alexandra , Saxena Amol , Hollander Karsten , Tenforde Adam S.
Published: July 2023

Bone stress injury (BSI) is a common overuse injury that can result in prolonged time away from sport. Limited studies have characterized the use of extracorporeal shockwave therapy (ESWT) for the treatment of BSI. The purpose of this study was to describe the use of ESWT for the management of BSI in runners. A retrospective chart review was performed to identify eligible patients in a single physician’s clinic from 1 August 2018 to 30 September 2022. BSI was identified in 40 runners with 41 injuries (28 females; average age and standard deviation: 30 ± 13 years; average pre-injury training 72 ± 40 km per week). Overall, 63% (n = 26) met the criteria for moderate- or high-risk Female or Male Athlete Triad categories. Runners started ESWT at a median of 36 days (IQR 11 to 95 days; range 3 days to 8 years) from BSI diagnosis. On average, each received 5 ± 2 total focused ESWT treatments. Those with acute BSI (ESWT started <3 months from BSI diagnosis) had an average return to run at 12.0 ± 7.5 weeks, while patients with delayed union (>3 months, n = 3) or non-union (>6 months, n = 9) had longer time for return to running (19.8 ± 14.8 weeks, p = 0.032). All runners returned to pain-free running after ESWT except one runner with non-union of grade 4 navicular BSI who opted for surgery. No complications were observed with ESWT. These findings suggest that focused ESWT may be a safe treatment for the management of BSI in runners.
The Dynamic Relationship between the Glymphatic System, Aging, Memory, and Sleep
Authors: Voumvourakis Konstantinos I. , Sideri Eleni , Papadimitropoulos Georgios N. , Tsantzali Ioanna , Hewlett Paul , Kitsos Dimitrios , Stefanou Marianna , Bonakis Anastasios , Giannopoulos Sotirios , Tsivgoulis Giorgios , Paraskevas George P.
Published: July 2023

The process of memory entails the activation of numerous neural networks and biochemical pathways throughout the brain. The phenomenon of memory decline in relation to aging has been the subject of extensive research for several decades. The correlation between the process of aging and memory is intricate and has various aspects to consider. Throughout the aging process, there are various alterations that take place within the brain and, as expected, affect other functions that have already been linked to memory and its function such as involving microcirculation and sleep. Recent studies provide an understanding of how these mechanisms may be interconnected through the relatively new concept of the glymphatic system. The glymphatic system is strongly correlated to sleep processes. Sleep helps the glymphatic system remove brain waste solutes. Astrocytes expand and contract to form channels for cerebrospinal fluid (CSF) to wash through the brain and eliminate waste. However, the details have not been totally elusive, but the discovery of what we call the glymphatic system enables us to connect many pieces of physiology to understand how such factors are interconnected and the interplay between them. Thus, the purpose of this review is to discuss how the glymphatic system, sleep, memory, and aging are interconnected through a network of complex mechanisms and dynamic interactions.
The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease
Authors: Ganizada Berta H. , Reesink Koen D. , Parikh Shaiv , Ramaekers Mitch J. F. G. , Akbulut Asim C. , Saraber Pepijn J. M. H. , Debeij Gijs P. ,   MUMC-TAA Student Team, Jaminon Armand M. , Natour Ehsan , Lorusso Roberto , Wildberger Joachim E. , Mees Barend , Schurink Geert Willem , Jacobs Michael J. , Cleutjens Jack , Krapels Ingrid , Gombert Alexander , Maessen Jos G. , Accord Ryan , Delhaas Tammo , Schalla Simon , Schurgers Leon J. , Bidar Elham
Published: July 2023

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5–5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold of <55 mm. Moreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue–cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell–matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.
A Holistic Approach to Hard-to-Treat Cancers: The Future of Immunotherapy for Glioblastoma, Triple Negative Breast Cancer, and Advanced Prostate Cancer
Authors: Puig-Saenz Carles , Pearson Joshua R. D. , Thomas Jubini E. , McArdle Stéphanie E. B.
Published: July 2023

Immunotherapy represents an attractive avenue for cancer therapy due to its tumour specificity and relatively low frequency of adverse effects compared to other treatment modalities. Despite many advances being made in the field of cancer immunotherapy, very few immunotherapeutic treatments have been approved for difficult-to-treat solid tumours such as triple negative breast cancer (TNBC), glioblastoma multiforme (GBM), and advanced prostate cancer (PCa). The anatomical location of some of these cancers may also make them more difficult to treat. Many trials focus solely on immunotherapy and have failed to consider or manipulate, prior to the immunotherapeutic intervention, important factors such as the microbiota, which itself is directly linked to lifestyle factors, diet, stress, social support, exercise, sleep, and oral hygiene. This review summarises the most recent treatments for hard-to-treat cancers whilst factoring in the less conventional interventions which could tilt the balance of treatment in favour of success for these malignancies.
Vertical Graphene-Based Printed Electrochemical Biosensor for Simultaneous Detection of Four Alzheimer’s Disease Blood Biomarkers
Authors: Li Mifang , Zeng Yu , Huang Zhen , Zhang Lingyan , Liu Yibiao
Published: July 2023

Early detection and timely intervention play a vital role in the effective management of Alzheimer’s disease. Currently, the diagnostic accuracy for Alzheimer’s disease based on a single blood biomarker is relatively low, and the combined use of multiple blood biomarkers can greatly improve diagnostic accuracy. Herein, we report a printed electrochemical biosensor based on vertical graphene (VG) modified with gold nanoparticles (VG@nanoAu) for the simultaneous detection of four Alzheimer’s disease blood biomarkers. The printed electrochemical electrode array was constructed by laser etching and inkjet printing. Then gold nanoparticles were modified onto the working electrode surface via electrodeposition to further improve the sensitivity of the sensor. In addition, the entire printed electrochemical sensing system incorporates an electrochemical micro-workstation and a smartphone. The customized electrochemical micro-workstation incorporates four electro-chemical control chips, enabling the sensor to simultaneously analyze four biomarkers. Consequently, the printed electrochemical sensing system exhibits excellent analytical performance due to the large surface area, biocompatibility, and good conductivity of VG@nanoAu. The detection limit of the sensing system for Aβ40, Aβ42, T-tau, and P-tau181 was 0.072, 0.089, 0.071, and 0.051 pg/mL, respectively, which meets the detection requirements of Alzheimer’s disease blood biomarkers. The printed electrochemical sensing system also exhibits good specificity and stability. This work has great value and promising prospects for early Alzheimer’s disease diagnosis using blood biomarkers.
Resveratrol Promotes Autophagy to Improve neuronal Injury in Parkinson’s Disease by Regulating SNHG1/miR-128-3p/SNCA Axis
Authors: Shen Dong-Fang , Qi Hui-Ping , Zhang Wei-Na , Sang Wen-Xu
Published: July 2023

Background: Parkinson’s disease (PD) is seriously threatening the health and life quality of the elderly, who have a high incidence and high disability rate. Resveratrol (RES) was reported to play a protective role in PD. However, the functions and potential mechanism of RES in PD remain unclear, which need to be further explored. Methods: Human neuroblastoma cells (SH-SY5Y and SK-N-SH) were subjected to 1-Methyl-4-phenylpyridium (MPP+) induction to construct a cell model of PD. Cell viability was evaluated using CCK-8. The gene expression was evaluated using qRT-PCR and western blot. Luciferase activity assay and RIP were performed to validate interactions among SNHG1, miR-128-3p and SNCA. Results: Our results exhibited that RES reduced SNHG1 and SNCA expression but elevated miR-128-3p expression in human neuroblastoma cells upon MPP+ induction. Functionally, RES resulted in the promotion of cell autophagy in MPP+-induced human neuroblastoma cells, while these influences were abolished by SNHG1 overexpression. Mechanistically, SNHG1 could indirectly elevate SNCA expression via sponging miR-128-3p. Moreover, SNCA overexpression reversed SNHG1 silencing-induced cell autophagy in MPP+-induced human neuroblastoma cells upon RES pre-incubation. Conclusions: RES prevented MPP+-induced repression of cell autophagy through inhibiting the SNHG1/miR-128-3p/SNCA axis, suggesting that RES might play a preventive effect on PD progression.
Measuring Engagement in Robot-Assisted Therapy for Autistic Children
Authors: Al-Nafjan Abeer , Alhakbani Noura , Alabdulkareem Amal
Published: July 2023

Children with autism face a range of challenges when it comes to verbal and nonverbal communication. It is essential that children participate in a variety of social, educational, and therapeutic activities to acquire knowledge that is essential for cognitive and social development. Recent studies have shown that children with autism may be interested in playing with an interactive robot. The robot can engage these children in ways that demonstrate and train essential aspects of human interaction, guiding them in therapeutic sessions to practice more complex forms of interaction found in social human-to-human interactions. This study sets out to investigate Robot-Assisted Autism Therapy (RAAT) and the use of artificial intelligence (AI) approaches for measuring the engagement of children during therapy sessions. The study population consisted of five native Arabic-speaking autistic children aged between 4 and 11 years old. The child–robot interaction was recorded by the robot camera and later used for analysis to detect engagement. The results show that the proposed system offers some accuracy in measuring the engagement of children with ASD. Our findings revealed that robot-assisted therapy is a promising field of application for intelligent social robots, especially to support autistic children in achieving their therapeutic and educational objectives.
Reward Behavior Disengagement, a Neuroeconomic Model-Based Objective Measure of Reward Pathology in Depression: Findings from the EMBARC Trial
Authors: Giles Michael A. , Cooper Crystal M. , Jha Manish K. , Chin Fatt Cherise R. , Pizzagalli Diego A. , Mayes Taryn L. , Webb Christian A. , Greer Tracy L. , Etkin Amit , Trombello Joseph M. , Chase Henry W. , Phillips Mary L. , McInnis Melvin G. , Carmody Thomas , Adams Phillip , Parsey Ramin V. , McGrath Patrick J. , Weissman Myrna , Kurian Benji T. , Fava Maurizio , Trivedi Madhukar H.
Published: July 2023

The probabilistic reward task (PRT) has identified reward learning impairments in those with major depressive disorder (MDD), as well as anhedonia-specific reward learning impairments. However, attempts to validate the anhedonia-specific impairments have produced inconsistent findings. Thus, we seek to determine whether the Reward Behavior Disengagement (RBD), our proposed economic augmentation of PRT, differs between MDD participants and controls, and whether there is a level at which RBD is high enough for depressed participants to be considered objectively disengaged. Data were gathered as part of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, a double-blind, placebo-controlled clinical trial of antidepressant response. Participants included 195 individuals with moderate to severe MDD (Quick Inventory of Depressive Symptomatology (QIDS–SR) score ≥ 15), not in treatment for depression, and with complete PRT data. Healthy controls (n = 40) had no history of psychiatric illness, a QIDS–SR score < 8, and complete PRT data. Participants with MDD were treated with sertraline or placebo for 8 weeks (stage I of the EMBARC trial). RBD was applied to PRT data using discriminant analysis, and classified MDD participants as reward task engaged (n = 137) or reward task disengaged (n = 58), relative to controls. Reward task engaged/disengaged groups were compared on sociodemographic features, reward–behavior, and sertraline/placebo response (Hamilton Depression Rating Scale scores). Reward task disengaged MDD participants responded only to sertraline, whereas those who were reward task engaged responded to sertraline and placebo (F(1293) = 4.33, p = 0.038). Reward task engaged/disengaged groups did not differ otherwise. RBD was predictive of reward impairment in depressed patients and may have clinical utility in identifying patients who will benefit from antidepressants.
Perceptions of Young Adults on the Critical Success Factors of the Build-to-Rent Housing Model in Sydney, Australia
Authors: Abidoye Rotimi Boluwatife , Ge Janet , Ahiadu Albert Agbeko , Adilieme Chibuikem Michael , Swanzy-Impraim Samuel
Published: July 2023

Amid Australia’s surging house prices, rental housing has become the safety net for young adults experiencing housing stress. The attention of policymakers is drawn towards the build-to-rent (BTR) housing model, a growing housing option for many young Australian adults. Although BTR’s integration into Australia’s housing and planning landscape is unfolding, the perception of young adults is lacking in policy reforms for this growing industry. This study examines the perspectives of young adults aged 18 to 34 years on the critical success factors (CSFs) of the BTR housing provision in Australia. The responses are analysed using an explanatory factor analysis, relative importance index, and ANOVA. Our findings show a critically low awareness of BTR among young adults in Australia. Respondents, between 18 and 24 years, are most concerned with public awareness, an indication of their desire for transparency and engagement in decision making at the policy level. Young adults rank regulation and government policy interventions as the most important CSF of BTR housing. This shows that they are more concerned about the affordability of BTR houses. This study concludes that young adults’ viewpoints on BTR are important in ongoing policy reforms. There is a need to ensure that this asset class is accessible and affordable to this target group.
Finite Element Analysis Using the Crack Strain Separation Model for Reinforced Concrete Membrane
Authors: Mitchell Jeffrey P. , Chae Seung-Un , Kim Yoo-Jae , Abaza Mohamed E.
Published: July 2023

This paper presents a finite element analysis of the bi-directional orthogonal model, which incorporates individual crack strain separation and tracking. The objective of this research is to expand the current shear friction model to manage bi-directional cracking at any angle, allowing for a more universal model that can be applied to intricate structures and non-proportional loading cases. The proposed model was initially developed as a total strain-based model, with the assumption that crack strains are equivalent to total strains, but it was subsequently recalculated to improve accuracy by separating crack strains from total strains. Furthermore, a separate crack strain formulation was created to account for strains in the concrete’s uncracked portions and locked-in crack strains. The article then discusses the testing of various convergence methods and loading programs to achieve high convergence. Comparative analyses of the generalized shear friction model with other models for crack orientation, and loading cases similar to those of a reinforced concrete membrane, are also presented. The MATLAB program successfully applied the bi-directional cracking model for one finite element under a uniform cyclical strain state, using a secant stiffness formulation.
Diffusion-Weighted MRI for Treatment Response Assessment in Osteoblastic Metastases—A Repeatability Study
Authors: Eveslage Maria , Rassek Philipp , Riegel Arne , Maksoud Ziad , Bauer Jochen , Görlich Dennis , Noto Benjamin
Published: July 2023

The apparent diffusion coefficient (ADC) is a candidate marker of treatment response in osteoblastic metastases that are not evaluable by morphologic imaging. However, it is unclear whether the ADC meets the basic requirement for reliable treatment response evaluation, namely a low variance of repeated measurements in relation to the differences found between viable and nonviable metastases. The present study addresses this question by analyzing repeated in vivo ADCmedian measurements of 65 osteoblastic metastases in nine patients, as well as phantom measurements. PSMA-PET served as a surrogate for bone metastasis viability. Measures quantifying repeatability were calculated and differences in mean ADC values according to PSMA-PET status were examined. The relative repeatability coefficient %RC of ADCmedian measurements was 5.8% and 12.9% for phantom and in vivo measurements, respectively. ADCmedian values of bone metastases ranged from 595×10−6mm2/s to 2090×10−6mm2/s with an average of 63% higher values in nonviable metastases compared with viable metastases (p < 0.001). ADC shows a small repeatability coefficient in relation to the difference in ADC values between viable and nonviable metastases. Therefore, ADC measurements fulfill the technical prerequisite for reliable treatment response evaluation in osteoblastic metastases.
Radical Tumor Denervation Activates Potent Local and Global Cancer Treatment
Authors: Mitsou John D. , Tseveleki Vivian , Dimitrakopoulos Foteinos-Ioannis , Konstantinidis Konstantinos , Kalofonos Haralabos
Published: July 2023

This preliminary study seeks to determine the effect of R&P denervation on tumor growth and survival in immunocompetent rats bearing an aggressive and metastatic breast solid tumor. A novel microsurgical approach was applied “in situ”, aiming to induce R&P denervation through the division of every single nerve fiber connecting the host with the primary tumor via its complete detachment and re-attachment, by resecting and reconnecting its supplying artery and vein (anastomosis). This preparation, known as microsurgical graft or flap, is radically denervated by definition, but also effectively delays or even impedes the return of innervation for a significant period of time, thus creating a critical and therapeutic time window. Mammary adenocarcinoma cells (HH-16.cl4) were injected into immunocompetent Sprague Dawley adult rats. When the tumors reached a certain volume, the subjects entered the study. The primary tumor, including a substantial amount of peritumoral tissue, was surgically isolated on a dominant artery and vein, which was resected and reconnected using a surgical microscope (orthotopic tumor auto-transplantation). Intending to simulate metastasis, two or three tumors were simultaneously implanted and only one was treated, using the surgical technique described herein. Primary tumor regression was observed in all of the microsurgically treated subjects, associated with a potent systemic anticancer effect and prolonged survival. In stark contrast, the subjects received a close to identical surgical operation; however, with the intact neurovascular connection, they did not achieve the therapeutic result. Animals bearing multiple tumors and receiving the same treatment in only one tumor exhibited regression in both the “primary” and remote- untreated tumors at a clinically significant percentage, with regression occurring in more than half of the treated subjects. A novel therapeutic approach is presented, which induces the permanent regression of primary and, notably, remote tumors, as well as, evidently, the naturally occurring metastatic lesions, at a high rate. This strategy is aligned with the impetus that comes from the current translational research data, focusing on the abrogation of the neuro–tumoral interaction as an alternative treatment strategy. More data regarding the clinical significance of this are expected to come up from a pilot clinical trial that is ongoing.
Trends in Diet and Cancer Research: A Bibliometric and Visualization Analysis
Authors: Giles Erin D. , Purcell Sarah A. , Olson Jessica , Vrieling Alina , Hirko Kelly A. , Woodruff Kary , Playdon Mary C. , Thomas Gwendolyn A. , Gilmore L. Anne , Moberly Heather K. , Newell-Fugate Annie E.
Published: July 2023

Diet plays a critical role for patients across the cancer continuum. The World Cancer Research Fund International and the American Cancer Society have published evidence supporting the role of nutrition in cancer prevention. We conducted an analysis of the literature on dietary nutrients and cancer to uncover opportunities for future research. The objective of the bibliometric analysis was to describe trends in peer-reviewed publications on dietary components and cancer and to highlight research gaps. PubMed was queried for manuscripts with diet- and cancer-related keywords and Medical Subject Headings (MeSH) terms. Metadata covering 99,784 publications from 6469 journals were analyzed to identify trends since 1970 on diet topics across 19 tumor types. Publications focused largely on breast, colorectal, and liver cancer, with fewer papers linking diet with other cancers such as brain, gallbladder, or ovarian. With respect to “unhealthy” diets, many publications focused on high-fat diets and alcohol consumption. The largest numbers of publications related to “healthy” diets examined the Mediterranean diet and the consumption of fruits and vegetables. These findings highlight the need for additional research focused on under-investigated cancers and dietary components, as well as dietary studies during cancer therapy and post-therapy, which may help to prolong survivorship.
Creating Opportunities to Eliminate Disparities in Lung Cancer Outcomes: A Call for Diverse Study Populations. Comment on Kohan et al. Disparity and Diversity in NSCLC Imaging and Genomics: Evaluation of a Mature, Multicenter Database. Cancers 2023, 15, 2096
Authors: Washington Caretia JeLayne , Braithwaite Dejana
Published: July 2023

We read with extensive interest the recently published paper, by Kohan et al., “Disparity and Diversity in NSCLC Imaging and Genomics: Evaluation of a Mature, Multicenter Database” [...]
Applications of Anti-Cytomegalovirus T Cells for Cancer (Immuno)Therapy
Authors: Britsch Isabel , van Wijngaarden Anne Paulien , Helfrich Wijnand
Published: July 2023

Infection with cytomegalovirus (CMV) is highly prevalent in the general population and largely controlled by CD8pos T cells. Intriguingly, anti-CMV T cells accumulate over time to extraordinarily high numbers, are frequently present as tumor-resident ‘bystander’ T cells, and remain functional in cancer patients. Consequently, various strategies for redirecting anti-CMV CD8pos T cells to eliminate cancer cells are currently being developed. Here, we provide an overview of these strategies including immunogenic CMV peptide-loading onto endogenous HLA complexes on cancer cells and the use of tumor-directed fusion proteins containing a preassembled CMV peptide/HLA-I complex. Additionally, we discuss conveying the advantageous characteristics of anti-CMV T cells in adoptive cell therapy. Utilization of anti-CMV CD8pos T cells to generate CAR T cells promotes their in vivo persistence and expansion due to appropriate co-stimulation through the endogenous (CMV-)TCR signaling complex. Designing TCR-engineered T cells is more challenging, as the artificial and endogenous TCR compete for expression. Moreover, the use of expanded/reactivated anti-CMV T cells to target CMV peptide-expressing glioblastomas is discussed. This review highlights the most important findings and compares the benefits, disadvantages, and challenges of each strategy. Finally, we discuss how anti-CMV T cell therapies can be further improved to enhance treatment efficacy.
Normo- or Hypo-Fractionated Photon or Proton Radiotherapy in the Management of Locally Advanced Unresectable Pancreatic Cancer: A Systematic Review
Authors: Elkhamisy Sally A. , Valentini Chiara , Lattermann Annika , Radhakrishna Ganesh , Künzel Luise A. , Löck Steffen , Troost Esther G. C.
Published: July 2023

LAPC is associated with a poor prognosis and requires a multimodal treatment approach. However, the role of radiation therapy in LAPC treatment remains controversial. This systematic review aimed to explore the role of proton and photon therapy, with varying radiation techniques and fractionation, in treatment outcomes and their respective toxicity profiles. Methods: Clinical studies published from 2012 to 2022 were systematically reviewed using PubMed, MEDLINE (via PubMed) and Cochrane databases. Different radiotherapy-related data were extracted and analyzed. Results: A total of 31 studies matched the inclusion criteria. Acute toxicity was less remarkable in stereotactic body radiotherapy (SBRT) compared to conventionally fractionated radiotherapy (CFRT), while in proton beam therapy (PBT) grade 3 or higher acute toxicity was observed more commonly with doses of 67.5 Gy (RBE) or higher. Late toxicity was not reported in most studies; therefore, comparison between groups was not possible. The range of median overall survival (OS) for the CFRT and SBRT groups was 9.3–22.9 months and 8.5–20 months, respectively. For the PBT group, the range of median OS was 18.4–22.3 months. Conclusion: CFRT and SBRT showed comparable survival outcomes with a more favorable acute toxicity profile for SBRT. PBT is a promising new treatment modality; however, additional clinical studies are needed to support its efficacy and safety.
The Mitochondrial ATP Synthase/IF1 Axis in Cancer Progression: Targets for Therapeutic Intervention
Authors: Domínguez-Zorita Sonia , Cuezva José
Published: July 2023

Cancer poses a significant global health problem with profound personal and economic implications on National Health Care Systems. The reprograming of metabolism is a major trait of the cancer phenotype with a clear potential for developing effective therapeutic strategies to combat the disease. Herein, we summarize the relevant role that the mitochondrial ATP synthase and its physiological inhibitor, ATPase Inhibitory Factor 1 (IF1), play in metabolic reprogramming to an enhanced glycolytic phenotype. We stress that the interplay in the ATP synthase/IF1 axis has additional functional roles in signaling mitohormetic programs, pro-oncogenic or anti-metastatic phenotypes depending on the cell type. Moreover, the same axis also participates in cell death resistance of cancer cells by restrained mitochondrial permeability transition pore opening. We emphasize the relevance of the different post-transcriptional mechanisms that regulate the specific expression and activity of ATP synthase/IF1, to stimulate further investigations in the field because of their potential as future targets to treat cancer. In addition, we review recent findings stressing that mitochondria metabolism is the primary altered target in lung adenocarcinomas and that the ATP synthase/IF1 axis of OXPHOS is included in the most significant signature of metastatic disease. Finally, we stress that targeting mitochondrial OXPHOS in pre-clinical mouse models affords a most effective therapeutic strategy in cancer treatment.
Patients Undergoing Systemic Anti-Cancer Therapy Who Require Surgical Intervention: What Surgeons Need to Know
Authors: Robinson Matthew D. , McNamara Mairéad G. , Clouston Hamish W. , Sutton Paul A. , Hubner Richard A. , Valle Juan W.
Published: July 2023

As part of routine cancer care, patients may undergo elective surgery with the aim of long-term cure. Some of these patients will receive systemic anti-cancer therapy (SACT) in the neoadjuvant and adjuvant settings. The majority of patients, usually with locally advanced or metastatic disease, will receive SACT with palliative intent. These treatment options are expanding beyond traditional chemotherapy to include targeted therapies, immunotherapy, hormone therapy, radionuclide therapy and gene therapy. During treatment, some patients will require surgical intervention on an urgent or emergency basis. This narrative review examined the evidence base for SACT-associated surgical risk and the precautions that a surgical team should consider in patients undergoing SACT.
A Recyclable Co-Fe Bimetallic Immobilized Cellulose Hydrogel Bead (CoFeO@CHB) to Boost Singlet Oxygen Evolution for Tetracycline Degradation
Authors: Chen Xinying , Zhang He , Xu Shizhe , Du Xiaoge , Zhang Kaida , Hu Chun-Po , Zhan Sihui , Mi Xueyue , Oh Wen Da , Hu Xiao , Pan Ziyong , Bao Yueping
Published: July 2023

In the current work, a novel Co-Fe bimetallic immobilized cellulose hydrogel bead (CoFeO@CHB) was prepared via in situ chemical precipitation followed by heat treatment and applied for tetracycline (TC) degradation in the presence of peroxymonosulfate (PMS). The characterization results indicated that the Co-Fe particles were evenly distributed within the porous cellulose hydrogel beads, without affecting their morphologies or crystal structures. During the TC degradation, the CoFeO@CHB/PMS system showed a high resistance and stability to different water bodies, and the common anions and natural organic matters showed a limited effect on TC degradation. The chemical quenching experiments (using chemicals to react with specific reactive species) as well as electron paramagnetic resonance (EPR) results showed that CoFeO@CHB can effectively active PMS to generate multiple reactive oxygen species (ROS, such as SO4•−, •OH and 1O2), in which the 1O2-dominated non-radical pathway played a vital role in TC degradation. Both Co and Fe were proposed as the active sites for PMS activation, and the CoFeO@CHB/PMS system showed a high potential in practical application due to its high selectivity and robustness with much less toxic intermediate products. Furthermore, a long-term continuous home-made dead-end filtration device was constructed to evaluate the stability and application potential of the CoFeO@CHB/PMS system, in which a >70% removal was maintained in a continuous 800 min filtration. These results showed the promising potential for cellulose hydrogel beads utilized as a metal-based nanomaterial substrate for organic degradation via PMS activation.
Early Administration of the Phytocannabinoid Cannabidivarin Prevents the Neurobehavioral Abnormalities Associated with the Fmr1-KO Mouse Model of Fragile X Syndrome
Authors: Premoli Marika , Fyke William , Bellocchio Luigi , Lemaire Valerie , Wolley-Roberts Marie , Bontempi Bruno , Pietropaolo Susanna
Published: July 2023

Phytocannabinoids, including the non-addictive cannabis component cannabidivarin (CBDV), have been reported to hold therapeutic potential in several neurodevelopmental disorders (NDDs). Nonetheless, the therapeutic value of phytocannabinoids for treating Fragile X syndrome (FXS), a major NDD, remains unexplored. Here, we characterized the neurobehavioral effects of CBDV at doses of 20 or 100 mg/kg in the Fmr1-knockout (Fmr1-KO) mouse model of FXS using two temporally different intraperitoneal regimens: subchronic 10-day delivery during adulthood (Study 1: rescue treatment) or chronic 5-week delivery at adolescence (Study 2: preventive treatment). Behavioral tests assessing FXS-like abnormalities included anxiety, locomotor, cognitive, social and sensory alterations. Expression of inflammatory and plasticity markers was investigated in the hippocampus and prefrontal cortex. When administered during adulthood (Study 1), the effects of CBDV were marginal, rescuing at the lower dose only the acoustic hyper-responsiveness of Fmr1-KO mice and at both doses their altered hippocampal expression of neurotrophins. When administered during adolescence (Study 2), CBDV at both doses prevented the cognitive, social and acoustic alterations of adult Fmr1-KO mice and modified the expression of several inflammatory brain markers in both wild-type littermates and mutants. These findings warrant the therapeutic potential of CBDV for preventing neurobehavioral alterations associated with FXS, highlighting the relevance of its early administration.
The REThink Online Therapeutic Game: A Usability Study
Authors: Iuga Ioana , Tomoiaga Cristina , David Oana
Published: July 2023

Background: Children and adolescents’ help-seeking behaviors are often limited by fear, uncertainty, and stigma, as well as challenges with finding the right intervention, help, and a lack of familiarity with the process. A promising direction for the development of therapeutic interventions targeted at children is embedding them into gamified interventions, known as therapeutic or serious games. The aim of this paper is to describe the protocol of the beta REThink therapeutic game and to evaluate the usability of the game in a sample of children and adolescents. Methods: The study was delivered in schools, where 137 children and adolescents aged between 9 and 16 years old played the levels of the REThink game, followed by filling in the usability questionnaire. Findings: The results show above average evaluations for all levels of the game, for every dimension evaluated, namely presence/immersion, enjoyment, learning effectiveness, narratives, goal clarity, adequacy of learning material, and motivation. This study contributes to the literature on the usability of cognitive behavioral therapy-based therapeutic games for improvements in the emotion regulation abilities of children and adolescents, which can guide researchers interested in testing the REThink game in different protocols, as well to encourage its use by mental health specialists and parents.
Self-Polarization in PbTiO3 Crystals Induced by Chemical Inhomogeneity in the Surface Layer
Authors: Stephanovich Vladimir A. , Rodenbücher Christian , Pilch Michal , Szade Jacek , Molak Andrzej , Bihlmayer Gustav , Szot Krzysztof
Published: July 2023

We study the so-called self-polarization phenomenon in single, electroded PbTiO3 crystals. In this case, near the electrodes, surface layers are formed with a chemically modified perovskite structure. This generates a built-in electric polarization, which cannot be switched permanently by an external electric field. While the initial samples, having two such surface layers with opposite directions of built-in polarization, exhibit ordinary symmetric hysteresis loops, the “asymmetric” samples, with one of these surface layers removed, show asymmetric hysteresis loops. To describe our experimental findings, we combine two kinds of models: one is phenomenological, utilizing the above general features; and the other is ab initio, taking into account the actual atomic structure at the bulk ferroelectric–surface layer–electrode interface. Namely, the ab initio calculations show that the electric polarization within the surface layer occurs due to the shifts of the relaxed Ti ions with respect to the oxygen ion octahedra on the PbO-terminated surface. We ascribe the self-polarization effect to the occurrence of the built-in electric field resulting from the formation of Pb-O planes within the surface layer.
An Evaluation of Interactive mHealth Applications for Adults Living with Cancer
Authors: Wasserman Sydney , Ould Brahim Lydia , Attiya Ameer , Belzile Eric , Lambert Sylvie D.
Published: July 2023

This study evaluated the quality and usefulness of interactive mobile health (mHealth) applications (apps) for adults with cancer. The PRISMA guidelines were followed to add rigor to the search, as well as to the data collection and analysis. The apps available in the most used app stores (Google Play and Apple) with interactive tailored features were identified. To supplement this, a Google web search was also conducted. The apps were evaluated for their quality using the validated Mobile App Rating Scale (MARS) and for their usefulness using a checklist of end users‘ desired features derived from the literature. The searches returned 3046 apps and 17 were retained for evaluation. The average quality score of the apps across the sample was 3.62/5 (SD 0.26, range: 3.14–4.06), with Outcomes4me scoring the highest. On average, the apps scored 50% (SD 2.5, range: 31–88%) on the usefulness checklist, with Cancer.net scoring the highest. The lowest-scoring categories were communications features on the usefulness checklist and “information” on the MARS, indicating areas for future work. The findings identified the apps of an acceptable quality and usefulness that could be recommended to those with cancer.
Perceptions of Cancer in Parents of Adolescent Daughters in Northwest Cameroon
Authors: Elit Laurie , Tum Eric , Ngalla Calvin , Fungchwi Glenn , Fokom Domgue Joel , Nouvet Elysee
Published: July 2023

Background: Cancer is a rapidly rising cause of morbidity and mortality in sub-Saharan Africa. Cervical cancer, in particular, is still one of the leading causes of mortality for women in this setting. The uptake of healthcare services is in part influenced by patients’ belief systems. We sought to better understand the perception of cancer in the Kom tribe of Northwest Cameroon. Methods: A qualitative research study was completed using a semi-structured interview guide and one-on-one interviews with 45 parents of girls aged 9–14 years. These girls were candidates for free HPV vaccination to prevent cervical cancer. The interviews were recorded, transcribed, and analyzed using ATLAS.ti 9. Results: Thirty-five mothers and ten fathers with a median age of 42 yo were interviewed from Mbingo, Belo, Njinikom, and Fundong. Half of the parents were farmers, with three being herbalists or traditional medicine doctors. Seventy-seven percent had either no or only primary school education. None had had cancer. All knew at least one person with cancer. The most common word for cancer in the Kom language is “ngoissu”. It can refer to a bad infection or cancer. The occurrence of ngoissu is the result of either a curse placed on you, ancestral retribution, or transgressing the ngoulatta (snail shell spoken over and usually placed in a garden). The implications are that treatment of ngoissu must involve the traditional doctor who determines the spiritual issue and prescribes a remedy (like a herb or tea) and/or an incantation. Within the context of cancer, this can lead to a delay in diagnosis until the disease is no longer curable by conventional therapies. Conclusion: Ways to bridge biomedical healthcare services and traditional medicine are needed, especially in tribal contexts where the latter is an integral part of daily life.