bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into Chemical Interactions and Related Toxicities of Deep Eutectic Solvents with Mammalian Cells Observed Using Synchrotron Macro–ATR–FTIR Microspectroscopy
Authors: Bryant Saffron J. , Shaw Z. L. , Huang Louisa Z. Y. , Elbourne Aaron , Abraham Amanda N. , Vongsvivut Jitraporn , Holt Stephen A. , Greaves Tamar L. , Bryant Gary
Published: May 2023

Deep eutectic solvents (DESs) and ionic liquids (ILs) are highly tailorable solvents that have shown a lot of promise for a variety of applications including cryopreservation, drug delivery, and protein stabilisation. However, to date, there is very limited information on the detailed interactions of these solvents with mammalian cells. In this work, we studied six DESs and one IL that show promise as cryoprotective agents, applying synchrotron macro–ATR–FTIR to examine their effects on key biochemical components of HaCat mammalian cells. These data were paired with resazurin metabolic assays and neutron reflectivity experiments to correlate cellular interactions with cellular toxicity. Stark differences were observed even between solvents that shared similar components. In particular, it was found that solvents that are effective cryoprotective agents consistently showed interactions with cellular membranes, while high toxicity correlated with strong interactions of the DES/IL with nucleic acids and proteins. This work sheds new light on the interactions between novel solvents and cells that may underpin future biomedical applications.
AI Machine Learning Technique Characterizes Potential Markers of Depression in Two Animal Models of Depression
Authors: Zhang Jing , Zhang Ran , Peng Ying , Aa Jiye , Wang Guangji
Published: May 2023

(1) Background: there is an urgent clinical need for rapid and effective antidepressants. (2) Methods: We employed proteomics to profile proteins in two animal models (n = 48) of Chronic Unpredictable Stress and Chronic Social Defeat Stress. Additionally, partial least squares projection to latent structure discriminant analysis and machine learning were used to distinguish the models and the healthy control, extract and select protein features and build biomarker panels for the identification of different mouse models of depression. (3) Results: The two depression models were significantly different from the healthy control, and there were common changes in proteins in the depression-related brain regions of the two models; i.e., SRCN1 was down-regulated in the dorsal raphe nucleus in both models of depression. Additionally, SYIM was up-regulated in the medial prefrontal cortex in the two depression models. Bioinformatics analysis suggested that perturbed proteins are involved in energy metabolism, nerve projection, etc. Further examination confirmed that the trends of feature proteins were consistent with mRNA expression levels. (4) Conclusions: To the best of our knowledge, this is the first study to probe new targets of depression in multiple brain regions of two typical models of depression, which could be targets worthy of study.
Modification of Body-Related Attentional Bias through Virtual Reality and Eye-Tracking in Healthy Participants: Implications for Anorexia Nervosa Treatments
Authors: Miquel-Nabau Helena , Briseño-Oloriz Natalia , Porras-Garcia Bruno , Ascione Mariarca , Meschberger-Annweiler Franck-Alexandre , Ferrer-Garcia Marta , Moreno-Sanchez Manuel , Serrano-Troncoso Eduardo , Carulla-Roig Marta , Gutiérrez Maldonado José
Published: May 2023

Cognitive biases have a significant impact on the etiology and treatment of eating disorders (EDs). These biases, including selective attentional bias (AB) to disliked body parts, may reinforce concerns about body shape, fear of gaining weight and body image disturbances and may contribute to dietary restriction and restraint. Decreasing AB could reduce core symptoms in anorexia nervosa (AN). This study represents a preliminary exploration aiming to assess whether AB towards weight-related (WR) and non-weight-related (NW) body parts could be reduced through an AB modification task in a virtual reality (VR) environment in healthy participants. A total of 54 female participants, aged 22.98 ± 1.89, were recruited. The task consisted of directing the participants’ attention towards all body parts equally in a VR setting. Eye-tracking (ET) measurements (complete fixation time [CFT] and number of fixations [NF]) were made before and after the task. The results showed a significant reduction of the AB in the two groups with an initial AB towards WR body parts or towards NW body parts. Participants showed a tendency to more balanced (non-biased) attention after the intervention. This study provides evidence of the usefulness of AB modification tasks in a non-clinical sample.
Unpacking the Relationship between Fear Motives and Self-Control Strategies among Managers: The Mediating Role of Intrusive Thoughts
Authors: Bakaç Cafer , Kehr Hugo M.
Published: May 2023

In motive research, only a handful of studies have appeared on the correlates and antecedents of fear motives. In this research, we contribute to both research and practice by investigating the relationships between fear motives, intrusive thoughts, self-control strategies, and positive affect. We propose that fear motives, similar to trait anxiety, are positively associated with intrusive thoughts and that intrusive thoughts, in return, are negatively related to the frequency with which individuals employ self-control strategies. Finally, we propose that the frequency of self-control strategies is positively associated with positive affect. To test these, two field studies with managers (Study 1: N = 100 and Study 2: N = 80) were conducted. Bayesian mediation analyses showed that in both Study 1 and Study 2, fear motives were positively associated with intrusive thoughts, and intrusive thoughts were negatively related to self-control strategies. Additionally, in line with predictions, intrusive thoughts mediated the fear motives-self-control strategies relation. Finally, in Study 2, we found self-regulation strategies to be significantly and positively associated with positive affect. The theoretical and practical implications of the study are discussed.
The Role of Platform Quality on Consumer Purchase Intention in the Context of Cross-Border E-Commerce: The Evidence from Africa
Authors: Han Lintong , Ma Yuehuan , Addo Prince Clement , Liao Miyan , Fang Jiaming
Published: May 2023

Africa, as one of the rapidly growing markets, presents a significant opportunity for cross-border e-commerce companies to penetrate their consumer market, which is in dire need of development. This study utilizes the Information System Success model to investigate the impact of cross-border e-commerce platform quality on consumers’ purchase intentions. Additionally, the study identifies the role of perceived value and trust in the purchase process. Moreover, the moderating effect of consumer acculturation on the relationship between cross-border platform quality and perceived value is examined. A total of 446 valid responses were obtained through a questionnaire survey and analyzed using structural equations. The findings reveal that platform information quality, system quality, and service quality significantly enhance consumers’ perceived value, thereby positively influencing their purchase intention. Furthermore, the results highlight the joint effect of perceived value and trust on purchase intention, and trust plays a mediating role in this relationship. The moderating effect of acculturation is also confirmed, indicating that it negatively moderates the impact of system and information quality on perceived value, while positively moderating the impact of service quality on perceived value. These findings complement and extend existing cross-border e-commerce research and provide valuable insights into the buying behavior of African consumers.
Why Does the Impact of Psychological Empowerment Increase Employees’ Knowledge-Sharing Intention? A Moderated Mediation Model of Belonging and Perceived Organizational Support
Authors: Seo Jungmin (Jamie)
Published: May 2023

This study examines the role of a sense of belonging in the relationship between the impact of psychological empowerment (PE) and employees’ knowledge-sharing intention (KSI). The research finding based on a survey sample of 422 full-time employees collected in South Korea reports that a sense of belonging is a key mediator that translates the effect of an employee’s perceived impact on the work environment into their KSI. The moderated mediation model shows that the mediating effect of a sense of belonging is more significant when employees perceive that organizational support is high. This study advances the literature on employee motivation and knowledge sharing by offering insights into the role played by employees’ sense of control and influence (i.e., impact) in developing social connections, which in turn influence their intention to share knowledge.
Brain Trauma and the Secondary Cascade in Humans: Review of the Potential Role of Vitamins in Reparative Processes and Functional Outcome
Authors: Denniss Rebecca J. , Barker Lynne A.
Published: May 2023

An estimated sixty-nine million people sustain a traumatic brain injury each year. Trauma to the brain causes the primary insult and initiates a secondary biochemical cascade as part of the immune and reparative response to injury. The secondary cascade, although a normal physiological response, may also contribute to ongoing neuroinflammation, oxidative stress and axonal injury, continuing in some cases years after the initial insult. In this review, we explain some of the biochemical mechanisms of the secondary cascade and their potential deleterious effects on healthy neurons including secondary cell death. The second part of the review focuses on the role of micronutrients to neural mechanisms and their potential reparative effects with regards to the secondary cascade after brain injury. The biochemical response to injury, hypermetabolism and excessive renal clearance of nutrients after injury increases the demand for most vitamins. Currently, most research in the area has shown positive outcomes of vitamin supplementation after brain injury, although predominantly in animal (murine) models. There is a pressing need for more research in this area with human participants because vitamin supplementation post-trauma is a potential cost-effective adjunct to other clinical and therapeutic treatments. Importantly, traumatic brain injury should be considered a lifelong process and better evaluated across the lifespan of individuals who experience brain injury.
Well-Being, Resilience and Social Support of Athletes with Disabilities: A Systematic Review
Authors: Mira Tânia , Costa Aldo M. , Jacinto Miguel , Diz Susana , Monteiro Diogo , Rodrigues Filipe , Matos Rui , Antunes Raúl
Published: May 2023

Sport for people with disabilities appears to play a positive role in the well-being, resilience and social support of athletes with disabilities. Thus, this systematic review aims to evaluate the effect of adapted sport on the well-being, resilience and social support in a population with disabilities. The Pubmed, Web of Science, Scopus and SportDiscus databases were used, with several descriptors and Boolean operators. A total of 287 studies were identified through searching the databases. After the data extraction process, twenty-seven studies were included for analysis. In general, these studies show that adapted sport has a positive impact on the levels of well-being, resilience and social support resources for people with disabilities, contributing to their personal development, quality of life and integration into society. Considering the impact on the variables studied, these results are important to support and encourage the development of adapted sport.
A Meta-Analysis of Evidence Synthesis for a Healthy Campus Built Environment by Adopting Active Design Approaches to Promote Physical Activity
Authors: Azeez Sweyda Abdullah , Mustafa Faris Ali , Ahmed Rizgar Maghded
Published: May 2023

The spread of chronic diseases, particularly obesity, has become a significant social issue on a global level concerning human inactivity and unhealthy behavior. The new approach to active design introduced by AIA and Sport England to increase human activity through physical activity in the built environment includes certifications such as Fitwell and LEED. An active design is any design feature that encourages physical activity, thus encouraging the user to be physically, mentally, and socially active in the built environment. This study aims to assemble evidence on the active design approach through physical activity in the campus built environment by using a meta-analysis approach and statistical analyses. There were 1993 papers identified during the search; following the screening, eligibility, and inclusion stages, 10 studies that addressed physical activity in colleges and universities were chosen. Findings indicate that physical activity has a positive impact on human health in the built environment. I² is (96.38%), which indicates considerable heterogeneity with p < 0.0001 and an absence of publication bias. Accordingly, a model was designed to integrate an active design approach and healthy behavior theories for future research. Overall, the evidence shows the importance of active design and physical activity for a healthy built environment to achieve healthy social behavior.
Distribution Characteristics of Cooking Oil Fume Particles in Residential Kitchens in Cold Regions
Authors: Yuan Yang , Wang Qingqin , Zhang Shuai , Zhu Neng , Zhao Mengmeng
Published: May 2023

A kitchen is an important part of a residence, and air quality in kitchens is a major factor affecting residents’ health and performance. Its influence is especially more evident in kitchens with typical Chinese cooking. Thus, it is important to understand distribution characteristics of oil fume particles in Chinese kitchens, and research on typical Chinese kitchen environments and movement characteristics of soot particles should be emphasized. Therefore, to understand the air pollution in kitchen environments, a full-scale experimental platform was built based on common Chinese-style residential kitchens to monitor the soot particles, explore the space–time distribution characteristics of the soot particles, and analyze the variation characteristics and distribution laws of number concentration (NC) and mass concentration (MC). The results indicated that NC0.3μm value fluctuated slightly during the whole cooking process, while NC0.3μm~0.5μm and NC0.5μm~1.0μm fluctuated sharply. During the peak period, NC0.3μm~0.5μm and NC0.5μm~1.0μm were significantly higher than those at the beginning and end of cooking (p < 0.05), and there was no significant difference between values of NC0.3μm~0.5μm and NC0.5μm~1.0μm at the beginning and end of cooking (p > 0.05 for both). NC0.3μm and NC0.3μm~0.5μm were significantly different between each position (p < 0.05 for all). There were also significant differences in NC0.3μm between pure meat dishes, pure vegetable dishes, and mixed dishes (p < 0.001). The proportion of cooking meat will significantly affect the composition and concentration of lampblack particles. Type of dishes is an important influencing factor for the emission rates of particulate pollutants. Small-sized lampblack particles were more likely to diffuse to the surroundings and affected the air quality of the whole room. Particulate matter in the kitchen space during the frying process is more harmful to the health of personnel.
Experimental and Numerical Study on Axial Compression Cold-Formed Steel Composite Wall under Concentrated Loads
Authors: Yao Bin , Fang Haojie , Qian Zhenghao , Wang Qiang , Sun Jian , Wang Weiyong
Published: May 2023

This paper presents the experimental and numerical studies in the investigation of the concentrated compressive behaviors of cold-formed steel-foam concrete composite wall. The failure modes, load–displacement curves, and load–strain curves of the specimens were obtained from the experiments. The infilled specimen failed due to distortional buckling of the end stud and cracking of the concrete near the corner of the wall. The strength of the high strength cold-formed steel was not being fully utilized. A finite element model was established by ABAQUS software and validated by the test results to investigate the effect of the concrete strength, steel strength, the spacing between stud openings, and the thickness of the concrete protective layer on the behaviors of the composite wall. The results indicate that the improvement of concrete strength has the most obvious effect on the bearing capacity of the composite wall, while the changes in steel strength, concrete cover thickness, and hole spacing have limited effects.
Prognosticators for Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Therapy and Pancreatectomy
Authors: Tong Yi Tat , Lai Zongshan , Katz Matthew H. G. , Prakash Laura R , Wang Hua , Chatterjee Deyali , Kim Michael , Tzeng Ching-Wei D. , Lee Jeffrey E. , Ikoma Naruhiko , Rashid Asif , Wolff Robert A. , Zhao Dan , Koay Eugene J. , Maitra Anirban , Wang Huamin
Published: May 2023

Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies.
Immune Checkpoint Profiling in Humanized Breast Cancer Mice Revealed Cell-Specific LAG-3/PD-1/TIM-3 Co-Expression and Elevated PD-1/TIM-3 Secretion
Authors: Bruss Christina , Kellner Kerstin , Albert Veruschka , Hutchinson James A. , Seitz Stephan , Ortmann Olaf , Brockhoff Gero , Wege Anja K.
Published: May 2023

Checkpoint blockade is particularly based on PD-1/PD-L1-inhibiting antibodies. However, an efficient immunological tumor defense can be blocked not only by PD-(L)1 but also by the presence of additional immune checkpoint molecules. Here, we investigated the co-expression of several immune checkpoint proteins and the soluble forms thereof (e.g., PD-1, TIM-3, LAG-3, PD-L1, PD-L2 and others) in humanized tumor mice (HTM) simultaneously harboring cell line-derived (JIMT-1, MDA-MB-231, MCF-7) or patient-derived breast cancer and a functional human immune system. We identified tumor-infiltrating T cells with a triple-positive PD-1, LAG-3 and TIM-3 phenotype. While PD-1 expression was increased in both the CD4 and CD8 T cells, TIM-3 was found to be upregulated particularly in the cytotoxic T cells in the MDA-MB-231-based HTM model. High levels of soluble TIM-3 and galectin-9 (a TIM-3 ligand) were detected in the serum. Surprisingly, soluble PD-L2, but only low levels of sPD-L1, were found in mice harboring PD-L1-positive tumors. Analysis of a dataset containing 3039 primary breast cancer samples on the R2 Genomics Analysis Platform revealed increased TIM-3, galectin-9 and LAG-3 expression, not only in triple-negative breast cancer but also in the HER2+ and hormone receptor-positive breast cancer subtypes. These data indicate that LAG-3 and TIM-3 represent additional key molecules within the breast cancer anti-immunity landscape.
The Subtype Identity of Testicular Cancer Cells Determines Their Immunostimulatory Activity in a Coculture Model
Authors: Gayer Fabian A. , Henkel Miriam , Luft Juliane , Reichardt Sybille D. , Fichtner Alexander , Legler Tobias J. , Reichardt Holger M.
Published: May 2023

Testicular germ cell cancer (TGCC) is subdivided into several subtypes. While seminomatous germ cell tumors (SGCT) are characterized by an intensive infiltration of immune cells which constitute a pro-inflammatory tumor micromilieu (TME), immune cells in non-seminomatous germ cell tumors (NSGCT) are differently composed and less abundant. Previously, we have shown that the seminomatous cell line TCam-2 promotes T cell and monocyte activation in a coculture model, resulting in mutual interactions between both cell types. Here we set out to compare this feature of TCam-2 cells with the non-seminomatous cell line NTERA-2. Peripheral blood T cells or monocytes cocultured with NTERA-2 cells failed to secrete relevant amounts of pro-inflammatory cytokines, and significantly downregulated the expression of genes encoding activation markers and effector molecules. In contrast, immune cells cocultured with TCam-2 cells produced IL-2, IL-6 and TNFα, and strongly upregulated the expression of multiple pro-inflammatory genes. Furthermore, the expression of genes involved in proliferation, stemness and subtype specification remained unaltered in NTERA-2 cells during coculture with T cells or monocytes, indicating the absence of mutual interactions. Collectively, our findings uncover fundamental differences between SGCT and NSGCT in their capability to generate a pro-inflammatory TME, which possibly impacts the clinical features and prognosis of both TGCC subtypes.
Vinblastine/Methotrexate for Debilitating and Progressive Plexiform Neurofibroma in Children and Young Adults with Neurofibromatosis Type 1: A Phase 2 Study
Authors: Kotch Chelsea , Wagner Kristina , Broad J. Harris , Dombi Eva , Minturn Jane E. , Phillips Peter , Smith Katherine , Li Yimei , Jacobs Ian N. , Elden Lisa M. , Fisher Michael J. , Belasco Jean
Published: May 2023

Limited therapies exist for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). For this reason, the activity of vinblastine (VBL) and methotrexate (MTX) was evaluated in children and young adults with NF1 and PN. Patients ≤ 25 years of age with progressive and/or inoperable NF1-PN received VBL 6 mg/m2 and MTX 30 mg/m2 weekly for 26 weeks, followed by every 2 weeks for 26 weeks. Objective response rate was the primary endpoint. Of 25 participants enrolled, 23 were evaluable. The median age of participants was 6.6 years (range 0.3–20.7). The most frequent toxicities were neutropenia and elevation of transaminases. On two-dimensional (2D) imaging, 20 participants (87%) had stable tumor, with a median time to progression of 41.5 months (95% confidence interval 16.9, 64.9). Two of eight participants (25%) with airway involvement demonstrated functional improvements including decreased positive pressure requirements and apnea-hypopnea index. A post hoc three-dimensional (3D) analysis of PN volumes was completed on 15 participants with amenable imaging; 7 participants (46%) had progressive disease on or by the end of therapy. VBL/MTX was well-tolerated but did not result in objective volumetric response. Furthermore, 3D volumetric analysis highlighted the lack of sensitivity of 2D imaging for PN response evaluation.
Autophagic-Related Proteins in Brain Gliomas: Role, Mechanisms, and Targeting Agents
Authors: Pizzimenti Cristina , Fiorentino Vincenzo , Franchina Mariausilia , Martini Maurizio , Giuffrè Giuseppe , Lentini Maria , Silvestris Nicola , Di Pietro Martina , Fadda Guido , Tuccari Giovanni , Ieni Antonio
Published: May 2023

The present review focuses on the phenomenon of autophagy, a catabolic cellular process, which allows for the recycling of damaged organelles, macromolecules, and misfolded proteins. The different steps able to activate autophagy start with the formation of the autophagosome, mainly controlled by the action of several autophagy-related proteins. It is remarkable that autophagy may exert a double role as a tumour promoter and a tumour suppressor. Herein, we analyse the molecular mechanisms as well as the regulatory pathways of autophagy, mainly addressing their involvement in human astrocytic neoplasms. Moreover, the relationships between autophagy, the tumour immune microenvironment, and glioma stem cells are discussed. Finally, an excursus concerning autophagy-targeting agents is included in the present review in order to obtain additional information for the better treatment and management of therapy-resistant patients.
CD51 Intracellular Domain Promotes Cancer Cell Neurotropism through Interacting with Transcription Factor NR4A3 in Colorectal Cancer
Authors: Huang Tianze , Lin Yanyun , Chen Junguo , Hu Jiancong , Chen Hao , Zhang Yanhong , Zhang Bin , He Xiaosheng
Published: May 2023

The abundant nervous system in intestine provides the basis for perineural invasion (PNI) of colorectal cancer (CRC). PNI is defined as the invasion of the nerves by cancer cells. Although PNI is already known to be an independent prognostic factor in CRC, the molecular mechanism underlying PNI remains obscure. In this study, we first demonstrated that CD51 could promote the neurotropism of tumor cells through cleavage with γ-secretase to generate an intracellular domain (ICD). Mechanistically, ICD of CD51 could bind to the transcription factor NR4A3, and act as a coactivator to promote the expression of downstream effectors, such as NTRK1, NTRK3, and SEMA3E. Pharmacological inhibition of γ-secretase impedes PNI mediated by CD51 in CRC both in vitro and in vivo and may become a potential therapeutic target for PNI in CRC.
Supported Ni Single-Atom Catalysts: Synthesis, Structure, and Applications in Thermocatalytic Reactions
Authors: Nishchakova Alina D. , Bulusheva Lyubov G. , Bulushev Dmitri A.
Published: May 2023

Nickel is a well-known catalyst in hydrogenation and dehydrogenation reactions. It is currently used in industrial processes as a homogenous and heterogeneous catalyst. However, to reduce the cost and increase the efficiency of catalytic processes, the development of single-atom catalysts (SACs) seems promising. Some SACs have already shown increased activity and stability as compared to nanoparticle catalysts. From year to year, the number of reports devoted to nickel SACs is growing rapidly. Among them, there are very few articles devoted to thermal catalysis, but at the same time, this subject is important. Thus, this review discusses recent advances in the synthesis, structure, and application of nickel SACs, mainly in catalytic hydrogenation/dehydrogenation reactions and in the dry reforming of methane. The collected and analyzed data can be useful in the development of novel nickel SACs for various processes.
Cellular Mechanisms Mediating Exercise-Induced Protection against Cardiotoxic Anthracycline Cancer Therapy
Authors: Dozic Sanela , Howden Erin J. , Bell James R. , Mellor Kimberley M. , Delbridge Lea M. D. , Weeks Kate L.
Published: May 2023

Anthracyclines such as doxorubicin are widely used chemotherapy drugs. A common side effect of anthracycline therapy is cardiotoxicity, which can compromise heart function and lead to dilated cardiomyopathy and heart failure. Dexrazoxane and heart failure medications (i.e., beta blockers and drugs targeting the renin–angiotensin system) are prescribed for the primary prevention of cancer therapy-related cardiotoxicity and for the management of cardiac dysfunction and symptoms if they arise during chemotherapy. However, there is a clear need for new therapies to combat the cardiotoxic effects of cancer drugs. Exercise is a cardioprotective stimulus that has recently been shown to improve heart function and prevent functional disability in breast cancer patients undergoing anthracycline chemotherapy. Evidence from preclinical studies supports the use of exercise training to prevent or attenuate the damaging effects of anthracyclines on the cardiovascular system. In this review, we summarise findings from experimental models which provide insight into cellular mechanisms by which exercise may protect the heart from anthracycline-mediated damage, and identify knowledge gaps that require further investigation. Improved understanding of the mechanisms by which exercise protects the heart from anthracyclines may lead to the development of novel therapies to treat cancer therapy-related cardiotoxicity.
New Insights into the Impact of Human Papillomavirus on Oral Cancer in Young Patients: Proteomic Approach Reveals a Novel Role for S100A8
Authors: Miranda-Galvis Marisol , Carneiro Soares Carolina , Moretto Carnielli Carolina , Ramalho Buttura Jaqueline , Sales de Sá Raisa , Kaminagakura Estela , Marchi Fabio Albuquerque , Paes Leme Adriana Franco , Lópes Pinto Clóvis A. , Santos-Silva Alan Roger , Moraes Castilho Rogerio , Kowalski Luiz Paulo , Squarize Cristiane Helena
Published: May 2023

Human papillomavirus (HPV) infection has recently been linked to a subset of cancers affecting the oral cavity. However, the molecular mechanisms underlying HPV-driven oral squamous cell carcinoma (OSCC) onset and progression are poorly understood. Methods: We performed MS-based proteomics profiling based on HPV status in OSCC in young patients, following biological characterization and cell assays to explore the proteome functional landscape. Results: Thirty-nine proteins are differentially abundant between HPV (+) and HPV (−) OSCC. Among them, COPS3, DYHC1, and S100A8 are unfavorable for tumor recurrence and survival, in contrast to A2M and Serpine1, low levels of which show an association with better DFS. Remarkably, S100A8 is considered an independent prognostic factor for lower survival rates, and at high levels, it alters tumor-associated immune profiling, showing a lower proportion of M1 macrophages and dendritic cells. HPV (+) OSCC also displayed the pathogen-associated patterns receptor that, when activated, triggered the S100A8 and NFκB inflammatory responses. Conclusion: HPV (+) OSCC has a peculiar microenvironment pattern distinctive from HPV (−), involving the expression of pathogen-associated pattern receptors, S100A8 overexpression, and NFκB activation and responses, which has important consequences in prognosis and may guide therapeutic decisions.
Protein Networks Associated with Native Metabotropic Glutamate 1 Receptors (mGlu1) in the Mouse Cerebellum
Authors: Mansouri Mahnaz , Kremser Leopold , Nguyen Thanh-Phuong , Kasugai Yu , Caberlotto Laura , Gassmann Martin , Sarg Bettina , Lindner Herbert , Bettler Bernhard , Carboni Lucia , Ferraguti Francesco
Published: May 2023

The metabotropic glutamate receptor 1 (mGlu1) plays a pivotal role in synaptic transmission and neuronal plasticity. Despite the fact that several interacting proteins involved in the mGlu1 subcellular trafficking and intracellular transduction mechanisms have been identified, the protein network associated with this receptor in specific brain areas remains largely unknown. To identify novel mGlu1-associated protein complexes in the mouse cerebellum, we used an unbiased tissue-specific proteomic approach, namely co-immunoprecipitation followed by liquid chromatography/tandem mass spectrometry analysis. Many well-known protein complexes as well as novel interactors were identified, including G-proteins, Homer, δ2 glutamate receptor, 14-3-3 proteins, and Na/K-ATPases. A novel putative interactor, KCTD12, was further investigated. Reverse co-immunoprecipitation with anti-KCTD12 antibodies revealed mGlu1 in wild-type but not in KCTD12-knock-out homogenates. Freeze-fracture replica immunogold labeling co-localization experiments showed that KCTD12 and mGlu1 are present in the same nanodomain in Purkinje cell spines, although at a distance that suggests that this interaction is mediated through interposed proteins. Consistently, mGlu1 could not be co-immunoprecipitated with KCTD12 from a recombinant mammalian cell line co-expressing the two proteins. The possibility that this interaction was mediated via GABAB receptors was excluded by showing that mGlu1 and KCTD12 still co-immunoprecipitated from GABAB receptor knock-out tissue. In conclusion, this study identifies tissue-specific mGlu1-associated protein clusters including KCTD12 at Purkinje cell synapses.
The Role of Eosinophil-Derived Neurotoxin and Vascular Endothelial Growth Factor in the Pathogenesis of Eosinophilic Asthma
Authors: Tota Maciej , Łacwik Julia , Laska Julia , Sędek Łukasz , Gomułka Krzysztof
Published: May 2023

Asthma is a chronic complex pulmonary disease characterized by airway inflammation, remodeling, and hyperresponsiveness. Vascular endothelial growth factor (VEGF) and eosinophil-derived neurotoxin (EDN) are two significant mediators involved in the pathophysiology of asthma. In asthma, VEGF and EDN levels are elevated and correlate with disease severity and airway hyperresponsiveness. Diversity in VEGF polymorphisms results in the variability of responses to glucocorticosteroids and leukotriene antagonist treatment. Targeting VEGF and eosinophils is a promising therapeutic approach for asthma. We identified lichochalcone A, bevacizumab, azithromycin (AZT), vitamin D, diosmetin, epigallocatechin gallate, IGFBP-3, Neovastat (AE-941), endostatin, PEDF, and melatonin as putative add-on drugs in asthma with anti-VEGF properties. Further studies and clinical trials are needed to evaluate the efficacy of those drugs. AZT reduces the exacerbation rate and may be considered in adults with persistent symptomatic asthma. However, the long-term effects of AZT on community microbial resistance require further investigation. Vitamin D supplementation may enhance corticosteroid responsiveness. Herein, anti-eosinophil drugs are reviewed. Among them are, e.g., anti-IL-5 (mepolizumab, reslizumab, and benralizumab), anti-IL-13 (lebrikizumab and tralokinumab), anti-IL-4 and anti-IL-13 (dupilumab), and anti-IgE (omalizumab) drugs. EDN over peripheral blood eosinophil count is recommended to monitor the asthma control status and to assess the efficacy of anti-IL-5 therapy in asthma.
“Combo” Multi-Target Pharmacological Therapy and New Formulations to Reduce Inflammation and Improve Endogenous Remyelination in Traumatic Spinal Cord Injury
Authors: Moretti Marzia , Caraffi Riccardo , Lorenzini Luca , Ottonelli Ilaria , Sannia Michele , Alastra Giuseppe , Baldassarro Vito Antonio , Giuliani Alessandro , Duskey Jason Thomas , Cescatti Maura , Ruozi Barbara , Aloe Luigi , Vandelli Maria Angela , Giardino Luciana , Tosi Giovanni , Calzà Laura
Published: May 2023

Spinal cord injury (SCI) is characterized by a cascade of events that lead to sensory and motor disabilities. To date, this condition is irreversible, and no cure exists. To improve myelin repair and limit secondary degeneration, we developed a multitherapy based on nanomedicines (NMeds) loaded with the promyelinating agent triiodothyronine (T3), used in combination with systemic ibuprofen and mouse nerve growth factor (mNGF). Poly-L-lactic-co-glycolic acid (PLGA) NMeds were optimized and loaded with T3 to promote sustained release. In vitro experiments confirmed the efficacy of T3-NMeds to differentiate oligodendrocyte precursor cells. In vivo rat experiments were performed in contusion SCI to explore the NMed biodistribution and efficacy of combo drugs at short- and long-term post-lesion. A strong anti-inflammatory effect was observed in the short term with a reduction of type M1 microglia and glutamate levels, but with a subsequent increase of TREM2. In the long term, an improvement of myelination in NG2-IR, an increase in MBP content, and a reduction of the demyelination area were observed. These data demonstrated that NMeds can successfully be used to obtain more controlled local drug delivery and that this multiple treatment could be effective in improving the outcome of SCIs.
Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes
Authors: Boeckhaus Jan , Mohr Lea , Dihazi Hassan , Tönshoff Burkhard , Weber Lutz T. , Pape Lars , Latta Kay , Fehrenbach Henry , Lange-Sperandio Baerbel , Kettwig Matthias , Staude Hagen , König Sabine , John-Kroegel Ulrike , Gellermann Jutta , Hoppe Bernd , Galiano Matthias , Haffner Dieter , Rhode Heidrun , Gross Oliver
Published: May 2023

The urinary albumin- and protein-to-creatinine ratios (UACR and UPCR, respectively) are key endpoints in most clinical trials assessing risk of progression of chronic kidney disease (CKD). For the first time, the current study compares the UACR versus the UPCR head-to-head at early stages of CKD, taking use of the hereditary podocytopathy Alport syndrome (AS) as a model disease for any CKD. Urine samples originated from the prospective randomized, controlled EARLY PRO-TECT Alport trial (NCT01485978). Urine samples from 47 children with confirmed diagnoses of AS at very early stages of CKD were divided according to the current stage of AS: stage 0 (UACR < 30 mg/g), stage 1 (30–300 mg/g) or stage 2 (>300 mg/g). The range of estimated glomerular filtration rate was 75–187.6 mL/min. The mean age was 10.4 ± 4.5 years. In children at stage 0, proteinuria in spot urine, confirmed in 24 h urine, was almost ten times higher than albuminuria (106.4 ± 42.2 vs. 12.5 ± 9.7; p < 0.05); it was “only” about three times higher in stage 1 (328.5 ± 210.1 vs. 132.3 ± 80.5; p < 0.05) and almost equal in stage 2 (1481.9 ± 983.4 vs. 1109.7 ± 873.6; p = 0.36). In 17 children, UACRs and UPCRs were measured simultaneously in 24 h urine and spot urine in the same study visit. Interestingly, the UACR (and UPCR) in 24 h urine vs. in spot urine varied by less than 10% (266.8 ± 426.4 vs. 291.2 ± 530.2). In conclusion, our study provides the first evidence that in patients with normal glomerular filtration rate (GFR) and low amounts of albuminuria, especially in children with podocytopathies such as AS, measuring the UACR and UPCR in spot urine is a reliable and convenient alternative to 24 h urine collection. Our study advocates both the UACR and the UPCR as relevant diagnostic biomarkers in future clinical trials in children with glomerular diseases because the UPCR seems to be a very significant parameter at very early stages of podocytopathies. The German Federal Ministry of Education and Research funded this trial (01KG1104).
Surface Functionalization of Calcium Phosphate Nanoparticles via Click Chemistry: Covalent Attachment of Proteins and Ultrasmall Gold Nanoparticles
Authors: Kostka Kathrin , Epple Matthias
Published: May 2023

Calcium phosphate nanoparticles (60 nm) were stabilized with either polyethyleneimine (PEI; polycationic electrolyte) or carboxymethylcellulose (CMC; polyanionic electrolyte). Next, a silica shell was added and terminated with either azide or alkyne groups via siloxane coupling chemistry. The particles were covalently functionalized by copper-catalyzed azide-alkyne cycloaddition (CuAAC; click chemistry) with proteins or gold nanoparticles that carried the complementary group, i.e., either alkyne or azide. The model proteins hemoglobin and bovine serum albumin (BSA) were attached as well as ultrasmall gold nanoparticles (2 nm). The number of protein molecules and gold nanoparticles attached to each calcium phosphate nanoparticle was quantitatively determined by extensive fluorescent labelling and UV–Vis spectroscopy on positively (PEI) or negatively (CMC) charged calcium phosphate nanoparticles, respectively. Depending on the cargo and the nanoparticle charge, this number was in the range of several hundreds to thousands. The functionalized calcium phosphate particles were well dispersible in water as shown by dynamic light scattering and internally amorphous as shown by X-ray powder diffraction. They were easily taken up by HeLa cells and not cytotoxic. This demonstrates that the covalent surface functionalization of calcium phosphate nanoparticles is a versatile method to create transporters with firmly attached cargo molecules into cells.
SARS-CoV-2 and Swabs: Disease Severity and the Numbers of Cycles of Gene Amplification, Single Center Experience
Authors: Falsaperla Raffaele , Sortino Vincenzo , Collotta Ausilia Desiree , Marino Silvia , Pavone Piero , Grassi Laura , Privitera Grete Francesca , Ruggieri Martino
Published: May 2023

Pediatric COVID-19 determines a mild clinical picture, but few data have been published about the correlation between disease severity and PCR amplification cycles of SARS-CoV-2 from respiratory samples. This correlation is clinically important because it permits the stratification of patients in relation to their risk of developing a serious disease. Therefore, the primary endpoint of this study was to establish whether disease severity at the onset, when evaluated with a LqSOFA score, correlated with the gene amplification of SARS-CoV-2. LqSOFA score, also named the Liverpool quick Sequential Organ Failure Assessment, is a pediatric score that indicates the severity of illness with a range from 0 to 4 that incorporates age-adjusted heart rate, respiratory rate, capillary refill and consciousness level (AVPU). The secondary endpoint was to determine if this score could predict the days of duration for symptoms and positive swabs. Our study included 124 patients aged between 0 and 18 years. The LqSOFA score was negatively correlated with the number of PCR amplification cycles, but this was not significant (Pearson’s index −0.14, p-value 0.13). Instead, the correlation between the LqSOFA score and the duration of symptoms was positively related and statistically significant (Pearson’s index 0.20, p-value 0.02), such as the correlation between the LqSOFA score and the duration of a positive swab (Pearson’s index 0.40, p-value < 0.01). So, the LqSOFA score upon admission may predict the duration of symptoms and positive swabs; the PCR amplification of SARS-CoV-2 appears not to play a key role at onset in the prediction of disease severity.
Enhancing Post-Operative Recovery in Spastic Diplegia through Physical Therapy Rehabilitation following Selective Dorsal Rhizotomy: A Case Report and Thorough Literature Analysis
Authors: Shahid Jawaria , Kashif Ayesha , Shahid Muhammad Kashif
Published: May 2023

Spasticity is a common issue among children, especially those with bilateral spastic cerebral palsy (CP). Selective dorsal rhizotomy (SDR) is a surgical procedure that is often used to decrease lower limb rigidity, alongside other treatment options such as intrathecal medication, peripheral nerve surgery, and deep brain stimulation (DBS). The objective of these therapies is to improve the standard of living for young individuals. This article intends to explain the motor deficits observed in spastic diplegia and a rehabilitation program using physical therapy after SDR. The information can help with counseling parents about the prognosis and developing a clinical treatment plan. The article presents a case study of a 12-year-old girl who recently underwent L3, L4, and L5 nerve root rhizotomy in the physical therapy department. It highlights the importance of long-term physical therapy follow-up and orthotic usage in the management of spastic diplegia.
State of the Art Bowel Management for Pediatric Colorectal Problems: Anorectal Malformations
Authors: Bokova Elizaveta , Svetanoff Wendy Jo , Lopez Joseph J. , Levitt Marc A. , Rentea Rebecca M.
Published: May 2023

Up to 79% of patients with anorectal malformations (ARMs) experience constipation and/or soiling after a primary posterior sagittal anoplasty (PSARP) and are referred to a bowel management program. We aim to report the recent updates in evaluating and managing these patients as part of the manuscript series on the current bowel management protocols for patients with colorectal diseases (ARMs, Hirschsprung disease, functional constipation, and spinal anomalies). The unique anatomic features of ARM patients, such as maldeveloped sphincter complex, impaired anal sensation, and associated spine and sacrum anomalies, indicate their bowel management plan. The evaluation includes an examination under anesthesia and a contrast study to exclude anatomic causes of poor bowel function. The potential for bowel control is discussed with the families based on the ARM index calculated from the quality of the spine and sacrum. The bowel management options include laxatives, rectal enemas, transanal irrigations, and antegrade continence enemas. In ARM patients, stool softeners should be avoided as they can worsen soiling.
City-Wise Assessment of Suitable CMIP6 GCM in Simulating Different Urban Meteorological Variables over Major Cities in Indonesia
Authors: Bhanage Vinayak , Lee Han Soo , Kubota Tetsu , Pradana Radyan Putra , Fajary Faiz Rohman , Arya Putra I Dewa Gede , Nimiya Hideyo
Published: May 2023

This study evaluates the performance of 6 global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6) for simulating temperature, precipitation, wind speed, and relative humidity over 29 cities in Indonesia. Modern-Era Retrospective Analysis for Research Applications (MERRA-2) was considered as reference data to assess the city-wise performance of surface air temperature, precipitation, wind speed, and relative humidity simulated by the CMIP6 GCMs during 1980–2014. Six statistical measures were computed in this process (mean annual, seasonal amplitude, mean annual bias, root mean square error, correlation coefficient, and standard deviation). For 29 cities, the mean annual values of surface air temperature, precipitation, wind speed, and relative humidity obtained from the GCMs range between 290 to 302 K, 100 cm to 450 cm, 1 to 6 m/s, and 70 to 94%, respectively. The correlation coefficient between the GCMs and the surface air temperature (precipitation) reanalysis dataset ranges from 0.3 to 0.85 (−0.14 to 0.77). The correlation coefficient for wind speed (relative humidity) varies from 0.2 to 0.6 and is positive in some cases (0.2 to 0.8). Subsequently, the relative error that combines the statistical measurement results was calculated for each city and meteorological variable. Results show that for surface air temperature and precipitation, the performance of TaiESM was outstanding over the 10 or more cities. In contrast, for wind speed and relative humidity, NOR-MM and MPI-HR were the best over 7 and 19 cities, respectively. For all the meteorological variables, the performance of AWI was found to be worst over all the cities. The outcomes of this study are essential for climate-resilience planning and GCM selection while performing downscaling experiments. It will also be useful for producing updated national climate change projections for each city in Indonesia and providing new insights into the climate system.