bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface-Based Cortical Measures in Multimodal Association Brain Regions Predict Chess Expertise
Authors: Trevisan Nicolò , Jaillard Assia , Cattarinussi Giulia , De Roni Prisca , Sambataro Fabio
Published: November 2022

The complex structure of the brain supports high-order cognition, which is crucial for mastering chess. Surface-based measures, including the fractional dimension (FD) and gyrification index (GI), may be more sensitive in detecting cortical changes relative to volumetric indexes. For this reason, structural magnetic resonance imaging data from 29 chess experts and 29 novice participants were analyzed using the CAT12 toolbox. FD and GI for each brain region were compared between the groups. A multivariate model was used to identify surface-based brain measures that can predict chess expertise. In chess experts, FD is increased in the left frontal operculum (p < 0.01), and this change correlates with the starting age of chess practice (ρ = −0.54, p < 0.01). FD is decreased in the right superior parietal lobule (p < 0.01). Chess expertise is predicted by the FD in a network of fronto-parieto-temporal regions and is associated with GI changes in the middle cingulate gyrus (p < 0.01) and the superior temporal sulcus (p < 0.01). Our findings add to the evidence that chess expertise is based on the complex properties of the brain surface of a network of transmodal association areas important for flexible high-level cognitive functions. Interestingly, these changes are associated with long-lasting practice, suggesting that neuroplastic effects develop over time.
Ultimate Bearing Capacity Analysis of Pile Caps with New Socket Connections
Authors: Ge Jiping , Lai Luqi , Liu Side , Yan Xingfei
Published: November 2022

Socket connection need a groove reserved in the cap to accommodate a bridge pier, which greatly weaken the vertical bearing capacity of the cap. The conventional treatment measure is to increase the thickness of the cap, and the corresponding cost will increase. The measures to enhance the vertical bearing capacity of socket caps without increasing the thickness of the cap were discussed in this paper, including a rough interface at the bottom of the pier, additional hanging bars, high-strength grouting material in the seam, and large-diameter metal corrugated pipes, etc. Based on a previous test, the finite element analysis of the vertical bearing capacity of pile caps with new socket connections was carried out. The analysis parameters included the construction method, steel bar diameter in the bottom of the cap, socket depth, thickness of the bottom plate, pile length, and friction coefficient, etc. The bearing capacity M–N relation of the full-scale model was also analyzed. Research indicated the vertical bearing capacity of the cap is mainly provided by rough interfaces, the bottom plate, and the additional hanging bars, and the contribution of the three parts was about 40%, 34%, and 26%; the vertical bearing capacity was proportional to the areas of steel bars on the cap and the thickness of the bottom plate, and was inversely proportional to the length of the pile. To obtain the vertical bearing capacity of the overall cast-in-place plan for the socket cap, the thickness of the cap needs to be increased by 27%. At last, a design formula for the calculation of the vertical bearing capacity was proposed.
Melanoma of the Upper Limb and Shoulder: A Surveillance, Epidemiology, and End Results Analysis of Epidemiology and Survival 2000–2019
Authors: Walz Solange N. , Martineau Jérôme , Scampa Matteo , Kalbermatten Daniel F. , Oranges Carlo M.
Published: November 2022

(1) Background: Melanoma is the most common life-threatening cancer among skin cancers. Almost all locations of the skin can be affected by melanoma, and the upper limbs are one of the most frequent locations. We aimed to study the epidemiology and survival outcomes of patients with melanoma localized in the upper extremities compared with other sites. (2) Methods: The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database is considered the most representative of the U.S. population; we extracted melanoma cases diagnosed between 2000 and 2019. Several characteristics, including demographical, pathological, and therapeutic, were recorded, and upper extremity melanomas and melanomas from other areas were compared. Overall survival was assessed, and the groups were compared. (3) Results: 69,436 patients had melanoma in the upper limbs and shoulders and 204,794 in other body parts. Overall, 35,267 patients with upper extremity melanoma were males, 34,169 were females, and the mean age was 60. For the rest of the body, there were 118,654 males and 86,140 females, with a mean age of 59. Surgery alone was the most commonly used treatment, while radiation therapy was the least used for all sites. Women appear to have better survival than men. Superficial spreading melanoma is the least lethal subtype, while nodular melanoma is the most dangerous. (4) Conclusion: Women under 50 are more at risk than men of the same age. The trend reverses after age 50 where men are at greater risk. In addition to gender and age, disease stage and major histologic subtypes influence survival.
Combined Vaccination with B Cell Peptides Targeting Her-2/neu and Immune Checkpoints as Emerging Treatment Option in Cancer
Authors: Tobias Joshua , Drinić Mirjana , Schmid Anna , Hladik Anastasiya , Watzenböck Martin L. , Battin Claire , Garner-Spitzer Erika , Steinberger Peter , Kundi Michael , Knapp Sylvia , Zielinski Christoph C. , Wiedermann Ursula
Published: November 2022

The application of monoclonal antibodies (mAbs), targeting tumor-associated (TAAs) or tumor-specific antigens or immune checkpoints (ICs), has shown tremendous success in cancer therapy. However, the application of mAbs suffers from a series of limitations, including the necessity of frequent administration, the limited duration of clinical response and the emergence of frequently pronounced immune-related adverse events. However, the introduction of mAbs has also resulted in a multitude of novel developments for the treatment of cancers, including vaccinations against various tumor cell-associated epitopes. Here, we reviewed recent clinical trials involving combination therapies with mAbs targeting the PD-1/PD-L1 axis and Her-2/neu, which was chosen as a paradigm for a clinically highly relevant TAA. Our recent findings from murine immunizations against the PD-1 pathway and Her-2/neu with peptides representing the mimotopes/B cell peptides of therapeutic antibodies targeting these molecules are an important focus of the present review. Moreover, concerns regarding the safety of vaccination approaches targeting PD-1, in the context of the continuing immune response, as a result of induced immunological memory, are also addressed. Hence, we describe a new frontier of cancer treatment by active immunization using combined mimotopes/B cell peptides aimed at various targets relevant to cancer biology.
Methylation Profiling in Diffuse Gliomas: Diagnostic Value and Considerations
Authors: Wenger Anna , Carén Helena
Published: November 2022

Diffuse gliomas cause significant morbidity across all age groups, despite decades of intensive research efforts. Here, we review the differences in diffuse gliomas in adults and children, as well as the World Health Organisation (WHO) 2021 classification of these tumours. We explain how DNA methylation-based classification works and list the methylation-based tumour types and subclasses for adult and paediatric diffuse gliomas. The benefits and utility of methylation-based classification in diffuse gliomas demonstrated to date are described. This entails the identification of novel tumour types/subclasses, patient stratification and targeted treatment/clinical management, and alterations in the clinical diagnosis in favour of the methylation-based over the histopathological diagnosis. Finally, we address several considerations regarding the use of DNA methylation profiling as a diagnostic tool, e.g., the threshold of the classifier, the calibrated score, tumour cell content and intratumour heterogeneity.
Spice-Derived Bioactive Compounds Confer Colorectal Cancer Prevention via Modulation of Gut Microbiota
Authors: Dacrema Marco , Ali Arif , Ullah Hammad , Khan Ayesha , Di Minno Alessandro , Xiao Jianbo , Martins Alice Maria Costa , Daglia Maria
Published: November 2022

Colorectal cancer (CRC) is the second most frequent cause of cancer-related mortality among all types of malignancies. Sedentary lifestyles, obesity, smoking, red and processed meat, low-fiber diets, inflammatory bowel disease, and gut dysbiosis are the most important risk factors associated with CRC pathogenesis. Alterations in gut microbiota are positively correlated with colorectal carcinogenesis, as these can dysregulate the immune response, alter the gut’s metabolic profile, modify the molecular processes in colonocytes, and initiate mutagenesis. Changes in the daily diet, and the addition of plant-based nutraceuticals, have the ability to modulate the composition and functionality of the gut microbiota, maintaining gut homeostasis and regulating host immune and inflammatory responses. Spices are one of the fundamental components of the human diet that are used for their bioactive properties (i.e., antimicrobial, antioxidant, and anti-inflammatory effects) and these exert beneficial effects on health, improving digestion and showing anti-inflammatory, immunomodulatory, and glucose- and cholesterol-lowering activities, as well as possessing properties that affect cognition and mood. The anti-inflammatory and immunomodulatory properties of spices could be useful in the prevention of various types of cancers that affect the digestive system. This review is designed to summarize the reciprocal interactions between dietary spices and the gut microbiota, and highlight the impact of dietary spices and their bioactive compounds on colorectal carcinogenesis by targeting the gut microbiota.
The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer
Authors: Yu Irene , Wu Rongrong , Tokumaru Yoshihisa , Terracina Krista P. , Takabe Kazuaki
Published: November 2022

The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of therapeutic responses, there has been an explosion of research into the mechanisms of microbial effects on CRC. Harnessing and reprogramming the microbiome may allow for the expansion of these successes to broader categories of CRC, the prevention of CRC in high-risk patients, and the enhancement of standard treatments. In this review, we pull together both well-documented phenomena and recent discoveries that pertain to the microbiome and CRC. We explore the microbial mechanisms associated with CRC pathogenesis and progression, recent advancements in CRC systemic therapy, potential options for diagnosis and prevention, as well as directions for future research.
Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2
Authors: Cao Fuyang , Yang Desong , Tang Feiyu , Lu Can , He Xiang , Chen Songming , Yang Zhanghuan , Gong Siyuan , Sun Lunquan , Enomoto Atsushi , Takahashi Masahide , Weng Liang
Published: November 2022

Girdin, an Akt substrate, has been reported to promote tumorigenesis in various tumors. However, the role of Girdin in a spontaneous tumor model has not yet been explored. Here, we studied the role of Girdin in lung adenocarcinoma (LUAD) using the autochthonous mouse model and found that Girdin led to LUAD progression and chemoresistance by enhancing the Warburg effect. Mechanistically, Girdin interacted with pyruvate kinase M2 (PKM2), which played a vital role in aerobic glycolysis. Furthermore, Girdin impaired Platelet Derived Growth Factor Receptor Beta (PDGFRβ) degradation, which in turn, promoted PKM2 tyrosine residue 105 (Y105) phosphorylation and inhibited PKM2 activity, subsequently promoting aerobic glycolysis in cancer cells. Taken together, our study demonstrates that Girdin is a crucial regulator of tumor growth and may be a potential therapeutic target for overcoming the resistance of LUAD cells to chemotherapy.
Nonsurgical Treatment Strategies for Elderly Head and Neck Cancer Patients: An Emerging Subject Worldwide
Authors: Okuda Hiroshi , Shibata Hirofumi , Watanabe Takahiro , Terazawa Kosuke , Mori Kenichi , Ueda Natsuko , Ohashi Toshimitsu , Ogawa Takenori
Published: November 2022

Consistent with the increasing rate of head and neck cancers among elderly adults, there has been an increase in the rate of those receiving nonsurgical treatments to maintain their function and quality of life. However, various problems, such as poor tolerance to chemoradiotherapy-related toxicity, are of greater concern in elderly adults than in younger individuals. In this review, we describe adverse events that should be particularly noted in elderly patients and provide an overview of countermeasures in nonsurgical treatments. We mainly focus on cisplatin-based chemoradiotherapy—the primary treatment for head and neck squamous cell carcinoma (HNSCC). Furthermore, we review the molecular targeted drugs and immune checkpoint inhibitors for elderly patients with HNSCC. Although the number of older patients is increasing worldwide, clinical trials aimed at determining the standard of care typically enroll younger or well-conditioned elderly patients. There is still very little evidence for treating elderly HNSCC older patients, and the question of optimal treatment needs to be explored.
Amino Acids in Cancer and Cachexia: An Integrated View
Authors: Ragni Maurizio , Fornelli Claudia , Nisoli Enzo , Penna Fabio
Published: November 2022

Rapid tumor growth requires elevated biosynthetic activity, supported by metabolic rewiring occurring both intrinsically in cancer cells and extrinsically in the cancer host. The Warburg effect is one such example, burning glucose to produce a continuous flux of biomass substrates in cancer cells at the cost of energy wasting metabolic cycles in the host to maintain stable glycemia. Amino acid (AA) metabolism is profoundly altered in cancer cells, which use AAs for energy production and for supporting cell proliferation. The peculiarities in cancer AA metabolism allow the identification of specific vulnerabilities as targets of anti-cancer treatments. In the current review, specific approaches targeting AAs in terms of either deprivation or supplementation are discussed. Although based on opposed strategies, both show, in vitro and in vivo, positive effects. Any AA-targeted intervention will inevitably impact the cancer host, who frequently already has cachexia. Cancer cachexia is a wasting syndrome, also due to malnutrition, that compromises the effectiveness of anti-cancer drugs and eventually causes the patient’s death. AA deprivation may exacerbate malnutrition and cachexia, while AA supplementation may improve the nutritional status, counteract cachexia, and predispose the patient to a more effective anti-cancer treatment. Here is provided an attempt to describe the AA-based therapeutic approaches that integrate currently distant points of view on cancer-centered and host-centered research, providing a glimpse of several potential investigations that approach cachexia as a unique cancer disease.
Can Pre-Operative Neutrophil-to-Lymphocyte Ratio (NLR) Help Predict Non-Metastatic Renal Carcinoma Recurrence after Nephrectomy? (UroCCR-61 Study)
Authors: Allenet Clément , Klein Clément , Rouget Benjamin , Margue Gaëlle , Capon Grégoire , Alezra Eric , Blanc Peggy , Estrade Vincent , Bladou Franck , Robert Grégoire , Bernhard Jean-Christophe
Published: November 2022

Recent studies suggested that the neutrophil-to-lymphocyte ratio (NLR) could play a key role in tumor initiation, progression and response to treatments. The main objective was to assess the prognostic value of the pre-operative NLR on recurrence-free survival (RFS) in patients with non-hereditary localized renal cell carcinoma. From the UroCCR database (NCT03293563), factors influencing the disease recurrence of consecutive patients who underwent nephrectomy for cT1-T4 N0M0 were analyzed using multi-variate cox regression and log-rank methods. We included 786 patients, among which 135 (17.2%) experienced a recurrence at a median time of 23.7 [8.5–48.6] months. RFS for patients with a pre-operative NLR of <2.7 was 94% and 88% at 3 and 5 years, respectively, versus 76% and 63% for patients with a NLR of ≥2.7 (p < 0.001, log-rank test). To predict the risk of post-operative recurrence, the NLR was combined with the UCLA integrated staging system (UISS), and we defined four groups of the UroCCR-61 predictive model. The RFS rates at 3 and 5 years were 100% and 97% in the very-low-risk group, 93% and 86% in the low-risk group, 78% and 68% in the intermediate-risk group and 63% and 46% in the high-risk group (p < 0.0001). The pre-operative NLR seems to be an inexpensive and easily accessible prognostic bio-marker for non-metastatic RCCs.
Systemic Therapy in Advanced Nodular Melanoma versus Superficial Spreading Melanoma: A Nation-Wide Study of the Dutch Melanoma Treatment Registry
Authors: Rauwerdink Daan Jan Willem , van Doorn Remco , van der Hage Jos , Van den Eertwegh Alfonsus J. M. , Haanen John B. A. G. , Aarts Maureen , Berkmortel Franchette , Blank Christian U. , Boers-Sonderen Marye J. , De Groot Jan Willem B. , Hospers Geke A. P. , de Meza Melissa , Piersma Djura , Van Rijn Rozemarijn S. , Stevense Marion , Van der Veldt Astrid , Vreugdenhil Gerard , Wouters Michel W. J. M. , Suijkerbuijk Karijn , van der Kooij Monique , Kapiteijn Ellen
Published: November 2022

Nodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry. The primary objectives were distant metastasis-free survival (DMFS) and overall survival (OS). In total, 1086 NM and 2246 SSM patients were included. DMFS was significantly shorter for advanced NM patients at 1.9 years (CI 95% 0.7–4.2) compared with SSM patients at 3.1 years (CI 95% 1.3–6.2) (p < 0.01). Multivariate survival analysis for immunotherapy and BRAF/MEKi demonstrated a hazard ratio for immunotherapy of 1.0 (CI 95% 0.85–1.17) and BRAF/MEKi of 0.95 (CI 95% 0.81–1.11). A shorter DMFS for NM patients developing advanced disease compared with SSM patients was observed, while no difference was observed in the efficacy of systemic immunotherapy or BRAF/MEKi between NM and SSM patients. Our results suggests that the worse overall survival of NM is mainly driven by propensity of metastatic outgrowth of NM after primary diagnosis.
Acute Pancreatitis Increases the Risk of Gastrointestinal Cancer in Type 2 Diabetic Patients: A Korean Nationwide Cohort Study
Authors: Choi Jin Ho , Paik Woo Hyun , Jang Dong Kee , Kim Min Kyu , Ryu Ji Kon , Kim Yong-Tae , Han Kyungdo , Lee Sang Hyub
Published: November 2022

The association between acute pancreatitis (AP) and gastrointestinal cancers in diabetic patients is currently not well understood. The study aim was to investigate the association between AP and gastrointestinal cancers in diabetic patients. Data from the Korean National Health Insurance Service database were analyzed. Participants with diabetes who underwent a health examination between 2009 and 2012 were followed up till December 2018. The primary outcome was the occurrence of gastrointestinal cancer. A total of 2,263,184 patients were included in the final analysis. Patients with a history of AP (n = 2390) were found to have a significantly higher risk of gastrointestinal cancer, except for esophageal cancer, as follows: gastric cancer (aHR = 1.637, 95% CI: 1.323–2.025), colorectal cancer (aHR = 2.183, 95% CI: 1.899–2.51), liver cancer (aHR = 2.216, 95% CI: 1.874–2.621), pancreatic cancer (aHR = 4.558, 95% CI: 4.078–5.095), bile duct cancer (aHR = 3.996, 95% CI: 3.091–5.269), and gallbladder cancer (aHR = 2.445, 95% CI: 1.459–4.099). The history of AP is associated with the increased risk of gastrointestinal cancer in diabetic patients. It is necessary to investigate the history of AP and more actively recommend screening for gastrointestinal cancers in such patients.
Approaches to the Management of Metastatic Adenoid Cystic Carcinoma
Authors: Lee Rex H. , Wai Katherine C. , Chan Jason W. , Ha Patrick K. , Kang Hyunseok
Published: November 2022

High rates of recurrence and distant metastasis are a foremost challenge in the management of adenoid cystic carcinoma (ACC), occurring in approximately 40% of all ACC patients. Despite the morbidity and mortality resulting from recurrent/metastatic (R/M) disease, there are no FDA-approved systemic agents for these patients. In this review, we summarize pertinent ACC pathophysiology and its implications for different systemic treatment regimens in R/M ACC. We review the evidence for the most widely used systemic agents — cytotoxic chemotherapy and tyrosine kinase inhibitors (TKIs) targeting VEGFR — in addition to immune checkpoint inhibitors and non-TKI biologic agents. Exciting emerging targets for R/M ACC, including inhibitors of Notch signaling, stemness, PRMT5, and Axl, are also discussed. Lastly, we review local therapies for small-volume lung disease in patients with oligometastatic ACC, specifically pulmonary metastasectomy and stereotactic body radiation therapy (SBRT). Future development of targeted molecular agents which exploit the underlying biology of this disease may yield novel therapeutic options to improve clinical outcomes in patients with R/M ACC.
Dietary EPA+DHA Mitigate Hepatic Toxicity and Modify the Oxylipin Profile in an Animal Model of Colorectal Cancer Treated with Chemotherapy
Authors: Monirujjaman Md , Bathe Oliver F. , Mazurak Vera C.
Published: November 2022

Irinotecan (CPT-11) and 5-fluorouracil (5-FU) are commonly used to treat metastatic colorectal cancer, but chemotherapy-associated steatosis/steatohepatitis (CASSH) frequently accompanies their use. The objective of this study was to determine effect of CPT-11+5-FU on liver toxicity, liver oxylipins, and cytokines, and to explore whether these alterations could be modified by dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oil (EPA+DHA). Tumor-bearing animals were administered CPT-11+5-FU and maintained on a control diet or a diet containing EPA+DHA (2.3 g/100 g). Livers were collected one week after chemotherapy for the analysis of oxylipins, cytokines, and markers of liver pathology (oxidized glutathione, GSSH; 4-hydroxynonenal, 4-HNE, and type-I collagen fiber). Dietary EPA+DHA prevented the chemotherapy-induced increases in liver GSSH (p < 0.011) and 4-HNE (p < 0.006). Compared with the tumor-bearing animals, ten oxylipins were altered (three/ten n-6 oxylipins were elevated while seven/ten n-3 oxylipins were reduced) following chemotherapy. Reductions in the n-3 fatty-acid-derived oxylipins that were evident following chemotherapy were restored by dietary EPA+DHA. Liver TNF-α, IL-6 and IL-10 were elevated (p < 0.05) following chemotherapy; dietary EPA+DHA reduced IL-6 (p = 0.09) and eotaxin (p = 0.007) levels. Chemotherapy-induced liver injury results in distinct alterations in oxylipins and cytokines, and dietary EPA+DHA attenuates these pathophysiological effects.
Search for Synergistic Drug Combinations to Treat Chronic Lymphocytic Leukemia
Authors: Hezkiy Eleonora Ela , Kumar Santosh , Gahramanov Valid , Yaglom Julia , Hesin Arkadi , Jadhav Suchita Suryakant , Guzev Ekaterina , Patel Shivani , Avinery Elena , Firer Michael A. , Sherman Michael Y.
Published: November 2022

Finding synergistic drug combinations is an important area of cancer research. Here, we sought to rationally design synergistic drug combinations with an inhibitor of BTK kinase, ibrutinib, which is used for the treatment of several types of leukemia. We (a) used a pooled shRNA screen to identify genes that protect cells from the drug, (b) identified protective pathways via bioinformatics analysis of these gene sets, and (c) identified drugs that inhibit these pathways. Based on this analysis, we established that inhibitors of proteasome and mTORC1 could synergize with ibrutinib both in vitro and in vivo. We suggest that FDA-approved inhibitors of these pathways could be effectively combined with ibrutinib for the treatment of chronic lymphocytic leukemia (CLL).
Tumor Immunogenic Cell Death as a Mediator of Intratumor CD8 T-Cell Recruitment
Authors: Roussot Nicolas , Ghiringhelli François , Rébé Cédric
Published: November 2022

The success of anticancer treatments relies on a long-term response which can be mediated by the immune system. Thus, the concept of immunogenic cell death (ICD) describes the capacity of dying cancer cells, under chemotherapy or physical stress, to express or release danger-associated molecular patterns (DAMPs). These DAMPs are essential to activate dendritic cells (DCs) and to stimulate an antigen presentation to CD8 cytotoxic cells. Then, activated CD8 T cells exert their antitumor effects through cytotoxic molecules, an effect which is transitory due to the establishment of a feedback loop leading to T-cell exhaustion. This phenomenon can be reversed using immune checkpoint blockers (ICBs), such as anti-PD-1, PD-L1 or CTLA-4 Abs. However, the blockade of these checkpoints is efficient only if the CD8 T cells are recruited within the tumor. The CD8 T-cell chemoattraction is mediated by chemokines. Hence, an important question is whether the ICD can not only influence the DC activation and resulting CD8 T-cell activation but can also favor the chemokine production at the tumor site, thus triggering their recruitment. This is the aim of this review, in which we will decipher the role of some chemokines (and their specific receptors), shown to be released during ICD, on the CD8 T-cell recruitment and antitumor response. We will also analyze the clinical applications of these chemokines as predictive or prognostic markers or as new targets which should be used to improve patients’ response.
Hyperglycemia Negatively Affects IPSC-Derived Myoblast Proliferation and Skeletal Muscle Regeneration and Function
Authors: Badu-Mensah Agnes , Valinski Paola , Parsaud Hemant , Hickman James J. , Guo Xiufang
Published: November 2022

Diabetic myopathy is a co-morbidity diagnosed in most diabetes mellitus patients, yet its pathogenesis is still understudied, which hinders the development of effective therapies. This project aimed to investigate the effect of hyperglycemia on human myoblast physiology, devoid of other complicating factors, by utilizing human myoblasts derived from induced pluripotent stem cells (iPSCs), in a defined in vitro system. IPSC-derived myoblasts were expanded under three glucose conditions: low (5 mM), medium (17.5 mM) or high (25 mM). While hyperglycemic myoblasts demonstrated upregulation of Glut4 relative to the euglycemic control, myoblast proliferation demonstrated a glucose dose-dependent impedance. Further cellular analysis revealed a retarded cell cycle progression trapped at the S phase and G2/M phase and an impaired mitochondrial function in hyperglycemic myoblasts. Terminal differentiation of these hyperglycemic myoblasts resulted in significantly hypertrophic and highly branched myotubes with disturbed myosin heavy chain arrangement. Lastly, functional assessment of these myofibers derived from hyperglycemic myoblasts demonstrated comparatively increased fatigability. Collectively, the hyperglycemic myoblasts demonstrated deficient muscle regeneration capability and functionality, which falls in line with the sarcopenia symptoms observed in diabetic myopathy patients. This human-based iPSC-derived skeletal muscle hyperglycemic model provides a valuable platform for mechanistic investigation of diabetic myopathy and therapeutic development.
microRNA Bioinformatics
Authors: Taguchi Y-h.
Published: November 2022

Firstly, I apologize for the delayed publication of this Special Issue in the form of a book title [...]
Natural Cross-Kingdom Spread of Apple Scar Skin Viroid from Apple Trees to Fungi
Authors: Tian Mengyuan , Wei Shuang , Bian Ruiling , Luo Jingxian , Khan Haris Ahmed , Tai Huanhuan , Kondo Hideki , Hadidi Ahmed , Andika Ida Bagus , Sun Liying
Published: November 2022

Viroids are the smallest known infectious agents that are thought to only infect plants. Here, we reveal that several species of plant pathogenic fungi that were isolated from apple trees infected with apple scar skin viroid (ASSVd) carried ASSVd naturally. This finding indicates the spread of viroids to fungi under natural conditions and further suggests the possible existence of mycoviroids in nature. A total of 117 fungal isolates were isolated from ASSVd-infected apple trees, with the majority (85.5%) being an ascomycete Alternaria alternata and the remaining isolates being other plant-pathogenic or -endophytic fungi. Out of the examined samples, viroids were detected in 81 isolates (69.2%) including A. alternata as well as other fungal species. The phenotypic comparison of ASSVd-free specimens developed by single-spore isolation and ASSVd-infected fungal isogenic lines showed that ASSVd affected the growth and pathogenicity of certain fungal species. ASSVd confers hypovirulence on ascomycete Epicoccum nigrum. The mycobiome analysis of apple tree-associated fungi showed that ASSVd infection did not generally affect the diversity and structure of fungal communities but specifically increased the abundance of Alternaria species. Taken together, these data reveal the occurrence of the natural spread of viroids to plants; additionally, as an integral component of the ecosystem, viroids may affect the abundance of certain fungal species in plants. Moreover, this study provides further evidence that viroid infection could induce symptoms in certain filamentous fungi.
Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer
Authors: Barresi Caterina , Rossiter Heidemarie , Buchberger Maria , Pammer Johannes , Sukseree Supawadee , Sibilia Maria , Tschachler Erwin , Eckhart Leopold
Published: November 2022

Autophagy is a ubiquitous degradation mechanism, which plays a critical role in cellular homeostasis. To test whether autophagy suppresses or supports the growth of tumors in the epidermis of the skin, we inactivated the essential autophagy gene Atg7 specifically in the epidermal keratinocytes of mice (Atg7∆ep) and subjected such mutant mice and fully autophagy-competent mice to tumorigenesis. The lack of epithelial Atg7 did not prevent tumor formation in response to 7, 12-dimethylbenz(a)anthracene (DMBA) as the initiator and 12-O tetradecanoylphorbol-13-acetate (TPA) as the promoter of tumor growth. However, the number of tumors per mouse was reduced in mice with epithelial Atg7 deficiency. In the K5-SOS EGFRwa2/wa2 mouse model, epithelial tumors were initiated by Son of sevenless (SOS) in response to wounding. Within 12 weeks after tumor initiation, 60% of the autophagy-competent K5-SOS EGFRwa2/wa2 mice had tumors of 1 cm diameter and had to be sacrificed, whereas none of the Atg7∆ep K5-SOS EGFRwa2/wa2 mice formed tumors of this size. In summary, the deletion of Atg7 reduced the growth of epithelial tumors in these two mouse models of skin cancer. Thus, our data show that the inhibition of autophagy limits the growth of epithelial skin tumors.
Increased Lipid Peroxidation and Lowered Antioxidant Defenses Predict Methamphetamine Induced Psychosis
Authors: Al-Hakeim Hussein Kadhem , Altufaili Mazin Fadhil , Almulla Abbas F. , Moustafa Shatha Rouf , Maes Michael
Published: November 2022

Background: a significant percentage of methamphetamine (MA) dependent patients develop psychosis. The associations between oxidative pathways and MA-induced psychosis (MIP) are not well delineated. Objective: the aim of this study is to delineate whether acute MA intoxication in MA dependent patients is accompanied by increased nitro-oxidative stress and whether the latter is associated with MIP. Method: we recruited 30 healthy younger males and 60 acutely intoxicated males with MA dependence and assessed severity of MA use and dependence and psychotic symptoms during intoxication, and serum oxidative toxicity (OSTOX) biomarkers including oxidized high (oxHDL) and low (oxLDL)-density lipoprotein, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO), and antioxidant defenses (ANTIOX) including HDL-cholesterol, zinc, glutathione peroxidase (GPx), total antioxidant capacity (TAC), and catalase-1. Results: a large part (50%, n = 30) of patients with MA dependence could be allocated to a cluster characterized by high psychosis ratings including delusions, suspiciousness, conceptual disorganization and difficulties abstract thinking and an increased OSTOX/ANTIOX ratio. Partial Least Squares analysis showed that 29.9% of the variance in MIP severity (a first factor extracted from psychosis, hostility, excitation, mannerism, and formal thought disorder scores) was explained by HDL, TAC and zinc (all inversely) and oxLDL (positively). MA dependence and dosing explained together 44.7% of the variance in the OSTOX/ANTIOX ratio. Conclusions: MA dependence and intoxication are associated with increased oxidative stress and lowered antioxidant defenses, both of which increase risk of MIP during acute intoxication. MA dependence is accompanied by increased atherogenicity due to lowered HDL and increased oxLDL and oxHDL.
A Comparison of the bébé VieScope™ and Direct Laryngoscope for Use While Wearing PPE-AGP: A Randomized Crossover Simulation Trial
Authors: Wieczorek Pawel , Szarpak Lukasz , Dabrowska Agata , Pruc Michal , Navolokina Alla , Raczynski Andrzej , Smereka Jacek
Published: November 2022

This study aimed to compare the intubation effectiveness of the bébé Vie Scope™ (VieScope) and direct laryngoscopy for emergency intubation in a pediatric manikin model performed by paramedics with and without personal protective equipment for aerosol generating procedures (PPE-AGP). Participants performed endotracheal intubation using VieScope and standard Macintosh laryngoscope (MAC) in two research scenarios: (1) without PPE-AGP, and (2) with PPE-AGP. Fifty-one paramedics without any previous experience with the VieScope participated in this study. In the PPE-AGP scenario, in the VieScope group, the percentage of successful tracheal intubation on the first attempt was higher compared to the MAC group (94.1 vs. 78.4%, p = 0.031), intubation time was shorter (29.8 vs. 33.9 s, p < 0.001), and percentage of glottic opening (POGO) score was higher 91.0 vs 77.8 (p < 0.001). On the Cormack–Lehane scale, intubation with VieScope intubation was associated with higher scores rated at 1 (64.7 vs. 29.4%) than in the MAC group (p = 0.001). For intubation in the non-PPE scenario, there were no statistically significant differences between VieScope and MAC in relation to above parameters. Summarize, the bébé VieScope™ under PPE-AGP wearing conditions has proven to be a useful device for airway management in children providing better visualization of the larynx, better intubation conditions, and a higher success rate of tracheal intubation on the first attempt and reduced intubation time compared to the standard Macintosh laryngoscope.
Recreational Soccer Training Effects on Pediatric Populations Physical Fitness and Health: A Systematic Review
Authors: Clemente Filipe Manuel , Moran Jason , Ramirez-Campillo Rodrigo , Oliveira Rafael , Brito João , Silva Ana Filipa , Badicu Georgian , Praça Gibson , Sarmento Hugo
Published: November 2022

This systematic review analyzed the effects of recreational soccer programs on physical fitness and health-related outcomes in youth populations. Studies were sought in the following databases: (i) PubMed, (ii) Scopus, (iii) SPORTDiscus, and (iv) Web of Science. The eligibility criteria included (1) population: youth (<18 years old) populations with no restrictions on sex or health condition; (2) intervention: exposure to a recreational soccer training program of at least four weeks duration; (3) comparator: a passive or active control group not exposed to a recreational soccer training program; (4) outcomes: physical fitness (e.g., aerobic, strength, speed, and change-of-direction) or health-related measures (e.g., body composition, blood pressure, heart rate variability, and biomarkers); (5) study design: a randomized parallel group design. The search was conducted on 6 September 2022 with no restrictions as to date or language. The risk of bias was assessed using the PEDro scale for randomized controlled studies. From a pool of 37,235 potentially relevant articles, 17 were eligible for inclusion in this review. Most of the experimental studies revealed the beneficial effects of recreational soccer for improving aerobic fitness and its benefits in terms of blood pressure and heart-rate markers. However, body composition was not significantly improved by recreational soccer. The main results revealed that recreational soccer training programs that are implemented twice a week could improve the generality of physical fitness parameters and beneficially impact cardiovascular health and biomarkers. Thus, recreational soccer meets the conditions for being included in the physical education curriculum as a good strategy for the benefit of the general health of children and young people.
Consensus on the Best Practice Guidelines for Psychomotor Intervention in Preschool Children with Autism Spectrum Disorder
Authors: Frazão Adriana , Santos Sofia , Rodrigues Ana , Brandão Teresa , Simões Celeste , Lebre Paula
Published: November 2022

Psychomotor intervention has been used to promote development by the enhancement of psychomotor and socio-emotional competence. However, studies with high-quality evidence, describing psychomotor-intervention processes and outcomes are scarce. Therefore, we aimed to generate expert consensus regarding psychomotor-intervention guidelines to support psychomotor therapists through the design and implementation of interventions for preschool (3–6 years old) children with autism spectrum disorder (ASD). A formal consensus process was carried out, using modified nominal group (phase I) and Delphi survey (phase II) techniques. We recruited 39 Portuguese experts in psychomotor intervention with preschool children with ASD in phase I. Experts participated in at least one of the five online meetings, discussing themes (e.g., objectives, methods, strategies) concerning psychomotor intervention with preschool children with ASD. A deductive thematic analysis from phase I resulted in 111 statements composing round 1 of the Delphi survey. Thirty-five experts completed round 1, and 23 round 2. The experts reached a consensus (agreement > 75%) on 88 statements, grouped under 16 sections, (e.g., intervention source, general setting, intended facilitation-style), reflecting generic psychomotor-intervention guidelines. Consensus guidelines may be used to support transparent and standard psychomotor interventions, although further studies should be undertaken to determine their efficacy.
Neurotoxic Impact of Individual Anesthetic Agents on the Developing Brain
Authors: Ji Dabin , Karlik Joelle
Published: November 2022

Concerns about the safety of anesthetic agents in children arose after animal studies revealed disruptions in neurodevelopment after exposure to commonly used anesthetic drugs. These animal studies revealed that volatile inhalational agents, propofol, ketamine, and thiopental may have detrimental effects on neurodevelopment and cognitive function, but dexmedetomidine and xenon have been shown to have neuroprotective properties. The neurocognitive effects of benzodiazepines have not been extensively studied, so their effects on neurodevelopment are undetermined. However, experimental animal models may not truly represent the pathophysiological processes in children. Multiple landmark studies, including the MASK, PANDA, and GAS studies have provided reassurance that brief exposure to anesthesia is not associated with adverse neurocognitive outcomes in infants and children, regardless of the type of anesthetic agent used.
Statistical Study on the Motivation of Patients in the Pediatric Dentistry
Authors: Josan Lucian , Bucur Sorana Maria , Păcurar Mariana , Teodorescu Elina , Sălcudean Andreea , Molnar Varlam Cristina Stanca , Ormenișan Alina
Published: November 2022

Our statistical study included 344 participants selected from the patients of the Pedodontics–Orthodontics Discipline of the Tîrgu-Mureş University of Medicine and Pharmacy. The patients’ age was between 6 and 18 years, with an average of 13.70 and a standard deviation of 4.62. The study participants were informed and agreed to complete two questionnaires of our conception regarding their health status, oral hygiene, and motivation for pedodontics or orthodontic treatment. The results of the two questionnaires were interpreted according to the gender and age of the patients. Data processing was performed with NCSS/PASS Dawson Edition statistical software, using the CHI2 test, considering a p of less than 0.05 as significant for comparative results. Results showed that girls were more motivated than boys in addressing pedodontic services due to dental, periodontal, and articular problems. Children, aged between 11 and 14 years, were less intrinsically motivated to solve oral health problems due to their low frequency. The intrinsic motivation for a more beautiful dentition was very strong, regardless of age and sex. Girls were more intrinsically motivated for orthodontic treatment than boys. There was a linear increase together in the age of those who wanted to improve their smile and facial appearance. Children between 11 and 14 years had the best self-perception of the appearance of their teeth, mouth, smile, and facial harmony. The strongest extrinsic motivation for orthodontic treatment came from parents or another doctor. The most important reason for orthodontics was dental malpositions, the last one was the improvement of masticatory efficiency. The extrinsic motivation from parents for orthodontics decreases linearly with age, along with the increase in motivation from the person with whom the participants relate emotionally and from the group of friends.
Corrosion Properties of DLC Film in Weak Acid and Alkali Solutions
Authors: Guo Dong , Zhang Shuling , Huang Tenglong , Wu Shuaizheng , Ma Xinghua , Guo Feng
Published: November 2022

As an important joint material, tantalum (Ta) needs to be studied intensively in terms of wear and corrosion resistance. Two films of Ta/Ti/DLC (diamond-like carbon) (referred to as TD film) and Ta/Ti/TiN/Ti/DLC (referred to as TTTD film) were prepared by magnetron sputtering technology, and their electrochemical corrosion performance in lactic acid and sodium bicarbonate solutions was also investigated. The morphology observation, electrochemical corrosion experiment, and static contact angle measurement were carried out using a scanning electron microscope, electrochemical workstation, and a contact angle meter. This paper mainly discusses and analyzes the corrosion influencing factors and corrosion mechanisms of these two films under two different environments. The 20-day immersion experiments show that the TD film in both solutions results in severe surface corrosion due to its loose structure and many internal defects. In contrast, the surface of the TTTD film with a dense structure, a multilayer structure, and a thicker thickness is not corroded under the same conditions. The electrochemical corrosion experiments show that the corrosion resistance of the TD film is worse than that of the Ta substrate, while the TTTD film has the strongest corrosion resistance, improving the corrosion resistance of the Ta substrate. Although the TD film had a higher sp3 content than the TTTD film, it does not provide protection to the Ta substrate due to increased structural defects in the TD film. The results of the contact angle show that the contact angle of the TTTD film is smaller than that of the TD film in both solutions. However, the TTTD film has the lowest roughness and the densest structure, and thus the TTTD film is more resistant to corrosion. It is finally concluded that the surface morphology and internal structure of the films are the main factors affecting corrosion resistance. This provides an important reference for the application of DLC film in weak alkaline and weak acid environments.
Auto-Encoder Classification Model for Water Crystals with Fine-Tuning
Authors: Hosni Mahmoud Hanan A. , Ali Hakami Nada
Published: November 2022

Water is one of the important, though scarce, resources on earth. The 2021 World Water Resource Report claims that environmental challenges threaten the sustainability of water resources. Therefore, it is vital to screen water quality to sustain water resources. Water quality is related to water crystal structure in its solid state. Intelligent models classify water crystals to predict their quality. Methods to analyze water crystals can aid in predicting water quality. Therefore, the major contribution of our research is the prediction of water crystal classes. The proposed model analyzes water crystals in solid states, employing image analysis and the deep learning method. The model specifies several feature groups, including crystal shape factors, solid-state features, crystal geometry and discrete cosine transform coefficients. The model utilizes feature fusion for better training. The proposed model utilized the EP water crystal dataset from the WC image depository and its accuracy was tested with the multi-feature Validation technique. The nature of our data inclined us to utilize F-Measure and sensitivity for the testing phase. Our proposed model outperformed other state of the art water crystal classification models by more than 6% in accuracy and 7% in f-measures, with performance exceeding 11% for triple feature fusion. Furthermore, our model was faster in training time (10% of the training time of the comparative models) and had 1.42 s classification time.