bluuebunny/crossref_metadata_2025 huggingface dataset:
Removal of p16INK4 Expressing Cells in Late Life has Moderate Beneficial Effects on Skeletal Muscle Function in Male Mice
Authors: Guzman Steve D. , Judge Jennifer , Shigdar Shahjahan M. , Paul Thomas A. , Davis Carol S. , Macpherson Peter C. , Markworth James F. , Van Remmen Holly , Richardson Arlan , McArdle Anne , Brooks Susan V.
Published: January 2022

Aging results in the progressive accumulation of senescent cells in tissues that display loss of proliferative capacity and acquire a senescence-associated secretory phenotype (SASP). The tumor suppressor, p16INK4A, which slows the progression of the cell cycle, is highly expressed in most senescent cells and the removal of p16-expressing cells has been shown to be beneficial to tissue health. Although much work has been done to assess the effects of cellular senescence on a variety of different organs, little is known about the effects on skeletal muscle and whether reducing cellular senescent load would provide a therapeutic benefit against age-related muscle functional decline. We hypothesized that whole-body ablation of p16-expressing cells in the advanced stages of life in mice would provide a therapeutic benefit to skeletal muscle structure and function. Treatment of transgenic p16-3MR mice with ganciclovir (GCV) from 20 to 26 months of age resulted in reduced p16 mRNA levels in muscle. At 26 months of age, the masses of tibialis anterior, extensor digitorum longus, gastrocnemius and quadriceps muscles were significantly larger in GCV-treated compared with vehicle-treated mice, but this effect was limited to male mice. Maximum isometric force for gastrocnemius muscles was also greater in GCV-treated male mice compared to controls. Further examination of muscles of GCV- and vehicle-treated mice showed fewer CD68-positive macrophages present in the tissue following GCV treatment. Plasma cytokine levels were also measured with only one, granulocyte colony stimulating factor (G-CSF), out of 22 chemokines analyzed was reduced in GCV-treated mice. These findings show that genetic ablation of p16+ senescent cells provides moderate and sex specific therapeutic benefits to muscle mass and function.
Convolutional Neural Network-Based Technique for Gaze Estimation on Mobile Devices
Authors: Akinyelu Andronicus A. , Blignaut Pieter
Published: January 2022

Eye tracking is becoming a very popular, useful, and important technology. Many eye tracking technologies are currently expensive and only available to large corporations. Some of them necessitate explicit personal calibration, which makes them unsuitable for use in real-world or uncontrolled environments. Explicit personal calibration can also be cumbersome and degrades the user experience. To address these issues, this study proposes a Convolutional Neural Network (CNN) based calibration-free technique for improved gaze estimation in unconstrained environments. The proposed technique consists of two components, namely a face component and a 39-point facial landmark component. The face component is used to extract the gaze estimation features from the eyes, while the 39-point facial landmark component is used to encode the shape and location of the eyes (within the face) into the network. Adding this information can make the network learn free-head and eye movements. Another CNN model was designed in this study primarily for the sake of comparison. The CNN model accepts only the face images as input. Different experiments were performed, and the experimental result reveals that the proposed technique outperforms the second model. Fine-tuning was also performed using the VGG16 pre-trained model. Experimental results show that the fine-tuned results of the proposed technique perform better than the fine-tuned results of the second model. Overall, the results show that 39-point facial landmarks can be used to improve the performance of CNN-based gaze estimation models.
Spindle Cell Lipoma of the Spermatic Cord: A Case Presentation and Literature Review of a Urologic Rarity and Radiologic Mimic of Malignant Liposarcoma
Authors: Dahmen Aaron , Juwono Timothy , Russo Nicholas W. , Patel Trushar
Published: January 2022

Background

Spindle cell lipomas are uncommon variants of typical lipomas, and presentation within the spermatic cord is exceedingly rare. Only three other cases have been reported in medical literature.

Case Presentation

We present the fourth case of spindle cell lipoma of the spermatic cord, which in this particular case had imaging findings suggestive of a malignant liposarcoma prompting radical orchiectomy. Histological investigation later concluded that this represented a benign, spindle cell lipoma of the spermatic cord as evidence by positive CD34 staining and microscopic analysis.

Conclusion

Although this particular variant of lipoma is rare, it is the hope that these findings contribute to the continued study of this disease process and can potentially prompt further evaluation prior to radical orchiectomy to limit patient morbidity.
Treatment of Mucous Cyst of the Distal Interphalangeal Joint With Osteophyte Excision and Joint Debridement
Authors: Fan Zhiyi , Chang Li , Su Xing , Yang Binbin , Zhu Zhe
Published: January 2022

Background

Mucous cyst of the distal interphalangeal joint (DMC) or interphalangeal connection of the thumb is common in middle-aged and elderly people, and it often occurs in the fingers of people with osteoarthritis (OA). Although there are many conservative treatments, DMC is usually treated by surgery. The common complications of surgical treatment are recurrence of DMC and skin necrosis. This article introduces the method and clinical effect of osteophyte excision and joint debridement in the treatment of DMC of the distal interphalangeal (DIP) joint.

Methods

In total, 19 cases of affected fingers made an 'S' incision in the DIP joint under local anesthesia to remove the osteophyte of the DIP joint, clean the dorsal joint capsule, wash the joint, and retain only the bilateral collateral ligament and extensor tendon device. It is suspected that the injured finger of the extensor tendon should be protected by external fixation.

Results

Out of 15 patients, 1 patient presented with partial skin necrosis that healed after dressing changes while the other patients recovered well. The visual analog scale (VAS) scores of all affected fingers after surgery were lower than those before the surgery (VAS score: 4.93 ± 0.88 vs. 4.07 ± 1.03, p < 0.05). The range of motion (ROM) of the affected finger decreased in one patient, and the post-operative activity of the other fingers increased in varying degrees (ROM: 67.60 ± 5.40 vs. 71.27 ± 7.06, p > 0.05).

Conclusions

Using osteophyte excision and joint debridement to treat DMC can avoid skin necrosis caused by cyst removal and can avoid the recurrence of DMC to the greatest extent, so it is a safe and effective way of treatment.
Surgical Treatment of a Giant Pleomorphic Adenoma of the Submandibular Gland: A Case Report
Authors: Wu Zehui , Liu Defeng , Peng Shihao , Wang Yuejun , Zhan Xiaolin , Li Laibin , Wan Hong , Li Yangyang , Guo Tao , Xu Aman
Published: January 2022

Pleomorphic adenomas (PAs) are the most common benign salivary neoplasms. PAs are generally slow-growing but may sometimes become aggressive and grow rapidly within a short period of time. Here, we report the case of an 83-year-old Chinese woman with an anterior neck mass that had been growing over the past 30 years. She felt uncomfortable because the mass had grown quite rapidly in the past year. The final diagnosis of a PA of the left submandibular gland was confirmed by histopathological and immunohistochemical examinations after surgical resection. Our patient recalled a history of an excision of a neck mass 40 years prior to presentation at another hospital. Based on our imaging findings and surgical findings, we speculate that the neck mass 40 years prior may also have been a PA. Our case reminds us the rare recurrence possibility of PAs, and early and thorough resection may have a good prognosis. In addition, to the best of our knowledge, this is the largest PA of the submandibular gland reported to date.
Obraz Bałkanów w twórczości Andrzeja Stasiuka i Małgorzaty
Rejmer
Authors: Nowaczewski Artur
Published: January 2022

The history of the term the Balkans and stigmatising images of the Balkan
area, created by travellers and writers from Western Europe, have been
described in works by Maria Todorova and Božidar Jezernik, which can already
be considered classical. After 1989, the image of the countries of Southeast
Europe in Poland was shaped under the infl uence of the Western discourse,
but it also had distinguishing features. These included the positioning of the
Balkans against of the myth of Central Europe and, to an extent, against the
common experience of communism. The most interesting (and infl uential)
narratives of Polish writers about the countries of this part of Europe are related
to the literary works by Andrzej Stasiuk and Małgorzata Rejmer. They also fi t
into the discussion about the boundaries of reportage that took place in Poland
in the 21st century after the death of Ryszard Kapuściński.
Пpiзвища yкраїнцiв cxiдної Галичини,
мотивованi влаcними iмeнами польського пoxoдження
Authors: Korpalo Oksana , Mytsan Daria
Published: January 2022

Surnames are an integral part of a person’s family identity and accompany
a person throughout their life. The study of regional anthroponymy is the basis
for dialectology, lexicography, etymology, word formation, and comparative
linguistics. This paper considers various principles of classifi cation of surnames
in general, and in particular it analyses surnames of Ukrainians from Eastern
Galicia, motivated by their own Polish names. The source of the surnames was
the telephone books of Ivano-Frankivsk, Lviv, and Ternopil.
The sample consists of 657 surnames, out of which 57 names were used:
41 male and 16 female ones. Most names became the basis for the formation of
not one but many surnames.
The materials and results of the research can be used in writing comparative
works on Ukrainian and Slavic onomastics, in research on lexicology and history
of language.
Detection of Potential Markers for Lip Vermilion Epithelium in Japanese Macaques Based on the Results of Gene Expression Profile
Authors: Kato Hiroko , Ling Yiwei , Hoshikawa Emi , Suzuki Ayako , Haga Kenta , Naito Eriko , Uenoyama Atsushi , Okuda Shujiro , Izumi Kenji
Published: January 2022

Development of effective in vitro human lip models, specific to the vermilion epithelium, has not progressed as much as that of skin and oral mucosa/gingiva models in vitro. Our histologic examination demonstrated that a Japanese macaque (male, 7 years and 9 months old) had vermilion in the lip distinct from adjacent skin and oral mucosa, resembling histological characteristics of the human lip. Therefore, in this study, we examined the gene expression profile of the three distinct epithelia (skin/vermilion/oral mucosa) within the lip of a Japanese macaque to explore a single potential marker of human vermilion epithelium. Six pairwise comparisons in the skin/vermilion/oral mucosa epithelium in vitro and in vivo revealed 69 differentially up-regulated genes in vermilion epithelium in vivo, in which a few unique genes were highly expressed when compared with both skin and oral mucosa epithelium in vivo using clustering analysis. However, we could not detect a single marker specific to vermilion epithelium supported by the gene expression profile of a Japanese macaque. Instead, the pair of keratin 10 and small proline-rich protein 3 resulted in a potential marker of vermilion epithelium in the human lip (female, 53-year-old) via a double-immunostaining technique. Nonetheless, our result may provide further clues leading to other potential markers of the vermilion epithelium.
Time to Shift Focus from Oxidative Stress to Redox Regulation in COPD
Authors: Reynaert Niki L.
Published: January 2022

Chronic obstructive pulmonary disease (COPD) is a non-communicable chronic disease that is top-ranking with respect to mortality and morbidity rates, posing an enormous burden on patients, caregivers and societies at large [...]
Quality of Public Housing in Singapore: Spatial Properties of Dwellings and Domestic Lives
Authors: Tamura Junko , Fang Kent
Published: January 2022

Singapore’s public housing policies are widely known for their success in providing housing for over 80% of the residential population, with most owning homes. Extensive housing schemes generally offer a set of fixed housing layouts; yet, at the microscale of an individual dwelling, alterations to the units can be made by rearranging the floor plans to reflect the usage patterns of the household, thus adding diversity to the fixed configuration. The aim of this paper is to identify associations among a housing unit’s spatial properties by analysing fixed configurations and altered floor plans as well as determining the spatial preferences of the inhabitants. The research methodology applied in this paper has been divided into two parts: spatial network analysis and survey analysis. In the spatial network analysis, the configurations of individual housing units and altered units were compared by translating floor plans into graphs. The survey functions as a qualitative analysis to relate the lifestyle patterns of contemporary society to housing configurations.
Biosynthesis and Biological Significances of LacdiNAc Group on N- and O-Glycans in Human Cancer Cells
Authors: Hirano Kiyoko , Furukawa Kiyoshi
Published: January 2022

An increasing number of studies have shown that the disaccharide GalNAcβ1→4GlcNAc (LacdiNAc) group bound to N- and O-glycans in glycoproteins is expressed in a variety of mammalian cells. Biosynthesis of the LacdiNAc group was well studied, and two β4-N-acetylgalactosaminyltransferases, β4GalNAcT3 and β4GalNAcT4, have been shown to transfer N-acetylgalactosamine (GalNAc) to N-acetylglucosamine (GlcNAc) of N- and O-glycans in a β-1,4-linkage. The LacdiNAc group is often sialylated, sulfated, and/or fucosylated, and the LacdiNAc group, with or without these modifications, is recognized by receptors and lectins and is thus involved in the regulation of several biological phenomena, such as cell differentiation. The occurrences of the LacdiNAc group and the β4GalNAcTs appear to be tissue specific and are closely associated with the tumor progression or regression, indicating that they will be potent diagnostic markers of particular cancers, such as prostate cancer. It has been demonstrated that the expression of the LacdiNAc group on N-glycans of cell surface glycoproteins including β1-integrin is involved in the modulation of their protein functions, thus affecting cellular invasion and other malignant properties of cancer cells. The biological roles of the LacdiNAc group in cancer cells have not been fully understood. However, the re-expression of the LacdiNAc group on N-glycans, which is lost in breast cancer cells by transfection of the β4GalNAcT4 gene, brings about the partial restoration of normal properties and subsequent suppression of malignant phenotypes of the cells. Therefore, elucidation of the biological roles of the LacdiNAc group in glycoproteins will lead to the suppression of breast cancers.
Longitudinal Monitoring of Intra-Tumoural Heterogeneity Using Optical Barcoding of Patient-Derived Colorectal Tumour Models
Authors: Shembrey Carolyn , Smith Jai , Grandin Mélodie , Williams Nathalia , Cho Hyun-Jung , Mølck Christina , Behrenbruch Corina , Thomson Benjamin NJ. , Heriot Alexander G. , Merino Delphine , Hollande Frédéric
Published: January 2022

Geno- and phenotypic heterogeneity amongst cancer cell subpopulations are established drivers of treatment resistance and tumour recurrence. However, due to the technical difficulty associated with studying such intra-tumoural heterogeneity, this phenomenon is seldom interrogated in conventional cell culture models. Here, we employ a fluorescent lineage technique termed “optical barcoding” (OBC) to perform simultaneous longitudinal tracking of spatio-temporal fate in 64 patient-derived colorectal cancer subclones. To do so, patient-derived cancer cell lines and organoids were labelled with discrete combinations of reporter constructs, stably integrated into the genome and thus passed on from the founder cell to all its clonal descendants. This strategy enables the longitudinal monitoring of individual cell lineages based upon their unique optical barcodes. By designing a novel panel of six fluorescent proteins, the maximum theoretical subpopulation resolution of 64 discriminable subpopulations was achieved, greatly improving throughput compared with previous studies. We demonstrate that all subpopulations can be purified from complex clonal mixtures via flow cytometry, permitting the downstream isolation and analysis of any lineages of interest. Moreover, we outline an optimized imaging protocol that can be used to image optical barcodes in real-time, allowing for clonal dynamics to be resolved in live cells. In contrast with the limited intra-tumour heterogeneity observed in conventional 2D cell lines, the OBC technique was successfully used to quantify dynamic clonal expansions and contractions in 3D patient-derived organoids, which were previously demonstrated to better recapitulate the heterogeneity of their parental tumour material. In summary, we present OBC as a user-friendly, inexpensive, and high-throughput technique for monitoring intra-tumoural heterogeneity in in vitro cell culture models.
Peripheral Blood Transcriptome in Breast Cancer Patients as a Source of Less Invasive Immune Biomarkers for Personalized Medicine, and Implications for Triple Negative Breast Cancer
Authors: Čelešnik Helena , Potočnik Uroš
Published: January 2022

Transcriptome studies of peripheral blood cells can advance our understanding of the systemic immune response to the presence of cancer and the mechanisms underlying cancer onset and progression. This enables the identification of novel minimally invasive immune biomarkers for early cancer detection and personalized cancer management and may bring forward new immunotherapy options. Recent blood gene expression analyses in breast cancer (BC) identified distinct patient subtypes that differed in the immune reaction to cancer and were distinct from the clinical BC subtypes, which are categorized based on expression of specific receptors on tumor cells. Introducing new BC subtypes based on peripheral blood gene expression profiles may be appropriate, since it may assist in BC prognosis, the identification of patients likely to benefit from immunotherapy, and treatment efficacy monitoring. Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous, and difficult-to-treat disease, and identification of novel biomarkers for this BC is crucial for clinical decision-making. A few studies have reported TNBC-enriched blood transcriptional signatures, mostly related to strong inflammation and augmentation of altered immune signaling, that can differentiate TNBC from other classical BC subtypes and facilitate diagnosis. Future research is geared toward transitioning from expression signatures in unfractionated blood cells to those in immune cell subpopulations.
Metabolic Phenotyping in Prostate Cancer Using Multi-Omics Approaches
Authors: Gómez-Cebrián Nuria , Poveda José Luis , Pineda-Lucena Antonio , Puchades-Carrasco Leonor
Published: January 2022

Prostate cancer (PCa), one of the most frequently diagnosed cancers among men worldwide, is characterized by a diverse biological heterogeneity. It is well known that PCa cells rewire their cellular metabolism to meet the higher demands required for survival, proliferation, and invasion. In this context, a deeper understanding of metabolic reprogramming, an emerging hallmark of cancer, could provide novel opportunities for cancer diagnosis, prognosis, and treatment. In this setting, multi-omics data integration approaches, including genomics, epigenomics, transcriptomics, proteomics, lipidomics, and metabolomics, could offer unprecedented opportunities for uncovering the molecular changes underlying metabolic rewiring in complex diseases, such as PCa. Recent studies, focused on the integrated analysis of multi-omics data derived from PCa patients, have in fact revealed new insights into specific metabolic reprogramming events and vulnerabilities that have the potential to better guide therapy and improve outcomes for patients. This review aims to provide an up-to-date summary of multi-omics studies focused on the characterization of the metabolomic phenotype of PCa, as well as an in-depth analysis of the correlation between changes identified in the multi-omics studies and the metabolic profile of PCa tumors.
T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis
Authors: Trailin Andriy , Červenková Lenka , Ambrozkiewicz Filip , Ali Esraa , Kasi Phanindra , Pálek Richard , Hošek Petr , Třeška Vladislav , Daum Ondrej , Tonar Zbyněk , Liška Václav , Hemminki Kari
Published: January 2022

In this retrospective study on 67 patients with hepatocellular carcinoma (HCC), after tumor resection, we evaluated the significance of CD3+ and CD8+ T-lymphocytes and CD20+ B-lymphocytes in tumor and non-tumor liver for time to recurrence (TTR), disease-free survival (DFS) and overall survival. After immunohistochemical staining, the density of nucleated lymphocyte profiles (QA) was estimated stereologically in the tumor center (TC), inner margin (inn M), outer margin (out M), peritumor and non-tumor liver. In TC, intermediate and high QA of CD8+ cells predicted longer TTR, whereas CD3+ and CD20+ were predictive only at high QA. DFS was predicted by high QA of CD3+, CD8+ and CD20+ cells in TC. The inn M harbored smaller QA of CD3+, CD8+ and CD20+ lymphocytes than out M. In contrast to out M, high T-cells’ QA and intermediate and high B-cell QA in inn M predicted longer TTR and DFS. High inn M/out M QA ratios of CD3+ and CD20+ cells were associated with longer TTR and DFS, whereas high inn M/out M QA ratio of CD8+ was predictive only for DFS. Patients with intermediate-high QA of combined CD8+ and CD20+ cells in inn M showed longer TTR and DFS, compared to CD8+-high or CD20+-high alone. Our findings highlight overall heterogeneity of the tumor invasive margin, the importance of inn M, and the predictive role of B-cells.
The Patient’s Point of View: COVID-19 and Neuroendocrine Tumor Disease
Authors: Krug Sebastian , Khosravian Maryam , Weissbach Julia , George Katharina , Damm Marko , Garbe Jakob , Walldorf Jens , Reuken Philipp A. , Amin Tania , Siebenhüner Alexander , Rosendahl Jonas , Gress Thomas M. , Michl Patrick , Schrader Jörg , Rinke Anja
Published: January 2022

The assessment of cancer patient care during the COVID-19 pandemic has been mainly reported from a physician’s perspective. Patients with rare tumor entities such as neuroendocrine tumors (NET), which require a complex and specialized care infrastructure, were highly affected by the COVID-19 crisis. Using a structured questionnaire consisting of a general section on the disease and a special COVID-19 section to record medical care, vaccination behavior as well as social and psycho-emotional parameters were collected from NET patients. The survey was distributed via direct medical contact and via the patient organization NETZWERK NeT. A total of 684 patients participated in the survey and 79.2% (n = 542) of the participants answered the questionnaire completely (54 questions). Patient characteristics were comparable to those in large NET registries. The majority of participants were patients with pancreatic and small bowel NET on somatostatin analogue (SSA) therapy. Medical care under COVID-19 was adequate and appointment cancellations and postponements were not common. Nevertheless, the majority of patients were worried about adequate treatment for their tumor disease during the crisis. Most of the participants considered themselves to be at risk of severe COVID-19 infection and were therefore very concerned. This was accompanied by an extremely high vaccination readiness rate of 90%. Increased distress in the social and psycho-emotional domains in the course of the crisis reflected a need for optimization in the medical care of NET patients, although the rate of COVID-19 positive participants was low (3.7%). Therefore, patient-reported measurements are required to identify and address all areas of medical care. Overall, our survey provides an essential contribution to the care of NET patients during the COVID-19 pandemic from the patient’s perspective.
PD-L1 near Infrared Photoimmunotherapy of Ovarian Cancer Model
Authors: Jin Jiefu , Sivakumar Ishwarya , Mironchik Yelena , Krishnamachary Balaji , Wildes Flonné , Barnett James D. , Hung Chien-Fu , Nimmagadda Sridhar , Kobayashi Hisataka , Bhujwalla Zaver M. , Penet Marie-France
Published: January 2022

(1) Background: Despite advances in surgical approaches and drug development, ovarian cancer is still a leading cause of death from gynecological malignancies. Patients diagnosed with late-stage disease are treated with aggressive surgical resection and chemotherapy, but recurrence with resistant disease is often observed following treatment. There is a critical need for effective therapy for late-stage ovarian cancer. Photoimmunotherapy (PIT), using an antibody conjugated to a near infrared (NIR) dye, constitutes an effective theranostic strategy to detect and selectively eliminate targeted cell populations. (2) Methods: Here, we are targeting program death ligand 1 (PD-L1) using NIR-PIT in a syngeneic mouse model of ovarian cancer. PD-L1 PIT-mediated cytotoxicity was quantified in RAW264.7 macrophages and ID8-Defb29-VEGF cells in culture, and in vivo with orthotopic ID8-Defb29-VEGF tumors. (3) Results: Treatment efficacy was observed both in vitro and in vivo. (4) Conclusions: Our data highlight the need for further investigations to assess the potential of using NIR-PIT for ovarian cancer therapy to improve the treatment outcome of ovarian cancer.
Targeted Delivery Methods for Anticancer Drugs
Authors: Veselov Valery V. , Nosyrev Alexander E. , Jicsinszky László , Alyautdin Renad N. , Cravotto Giancarlo
Published: January 2022

Several drug-delivery systems have been reported on and often successfully applied in cancer therapy. Cell-targeted delivery can reduce the overall toxicity of cytotoxic drugs and increase their effectiveness and selectivity. Besides traditional liposomal and micellar formulations, various nanocarrier systems have recently become the focus of developmental interest. This review discusses the preparation and targeting techniques as well as the properties of several liposome-, micelle-, solid-lipid nanoparticle-, dendrimer-, gold-, and magnetic-nanoparticle-based delivery systems. Approaches for targeted drug delivery and systems for drug release under a range of stimuli are also discussed.
Advances in and the Applicability of Machine Learning-Based Screening and Early Detection Approaches for Cancer: A Primer
Authors: Benning Leo , Peintner Andreas , Peintner Lukas
Published: January 2022

Despite the efforts of the past decades, cancer is still among the key drivers of global mortality. To increase the detection rates, screening programs and other efforts to improve early detection were initiated to cover the populations at a particular risk for developing a specific malignant condition. These diagnostic approaches have, so far, mostly relied on conventional diagnostic methods and have made little use of the vast amounts of clinical and diagnostic data that are routinely being collected along the diagnostic pathway. Practitioners have lacked the tools to handle this ever-increasing flood of data. Only recently, the clinical field has opened up more for the opportunities that come with the systematic utilisation of high-dimensional computational data analysis. We aim to introduce the reader to the theoretical background of machine learning (ML) and elaborate on the established and potential use cases of ML algorithms in screening and early detection. Furthermore, we assess and comment on the relevant challenges and misconceptions of the applicability of ML-based diagnostic approaches. Lastly, we emphasise the need for a clear regulatory framework to responsibly introduce ML-based diagnostics in clinical practice and routine care.
Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?
Authors: Verhulst Emile , Garnier Delphine , De Meester Ingrid , Bauvois Brigitte
Published: January 2022

Cell surface proteases (also known as ectoproteases) are transmembrane and membrane-bound enzymes involved in various physiological and pathological processes. Several members, most notably dipeptidyl peptidase 4 (DPP4/CD26) and its related family member fibroblast activation protein (FAP), aminopeptidase N (APN/CD13), a disintegrin and metalloprotease 17 (ADAM17/TACE), and matrix metalloproteinases (MMPs) MMP2 and MMP9, are often overexpressed in cancers and have been associated with tumour dysfunction. With multifaceted actions, these ectoproteases have been validated as therapeutic targets for cancer. Numerous inhibitors have been developed to target these enzymes, attempting to control their enzymatic activity. Even though clinical trials with these compounds did not show the expected results in most cases, the field of ectoprotease inhibitors is growing. This review summarizes the current knowledge on this subject and highlights the recent development of more effective and selective drugs targeting ectoproteases among which small molecular weight inhibitors, peptide conjugates, prodrugs, or monoclonal antibodies (mAbs) and derivatives. These promising avenues have the potential to deliver novel therapeutic strategies in the treatment of cancers.
Constitutive Changes in Nutrients and Phytochemicals in Kernels of Aluminium-Tolerant Maize (Zea mays L.)
Authors: Ortiz-Islas Sofia , Serna-Saldivar Sergio , García-Lara Silverio
Published: January 2022

Maize (Zea mays L.) is among the three most important food crops worldwide. Maize growth is affected by high aluminium content in acid soils, which constitute nearly 50% of the world’s cultivable area. Therefore, the cultivation of aluminium-tolerant maize hybrids could be a healthier alternative and an attractive food source in these regions. In this regard, to produce hybrids kernels, 16 inbred lines aluminium-tolerant (Al-T) and aluminium-susceptible (Al-S) maize were screened for their constitutive patterns of selected nutrients and phytochemicals. Proximate analysis, free phenolic acids (FPA) and cell wall-bound phenolic acids (CPA) contents, as well as antioxidant capacity (AOX) were assayed in the anatomical kernel parts (pericarp, endosperm, and germ). Kernels of Al-T maize contained significantly higher germ protein, oil, and fibre (2.9, 3.0, and 0.5%, respectively) than Al-S kernels (1.9, 1.8, and 0.3%, respectively). Importantly, the nutraceutical contents in terms of pericarp FPA and germ CPA were significantly higher in kernels belonging to Al-T maize (92 mg and 140 mg EGA/100 g). The highest AOX was observed in germ CPA of Al-T kernels (9.0 mmol TE/100 g). The results herein indicate that Al-tolerance mechanisms induce positive changes in the nutrients and phytochemicals; this implies that the hybrids generated using Al-T maize inbred lines could emerge as an attractive source of nutrients and phytochemicals in farming regions containing acid soils.
Diversity Patterns of Late Jurassic Chondrichthyans: New Insights from a Historically Collected Hybodontiform Tooth Assemblage from Poland
Authors: Stumpf Sebastian , Meng Stefan , Kriwet Jürgen
Published: January 2022

Here, we provide a detailed taxonomic reassessment of a historically collected chondrichthyan dental assemblage from the lower Kimmeridgian of Czarnogłowy in north-western Poland and discuss its significance for better understanding hybodontiform diversity patterns prior to their post-Jurassic decline in fully marine environments. In spite of its low taxonomic diversity, consisting of four large-toothed taxa (viz., Strophodus udulfensis, Asteracanthus ornatissimus, Planohybodus sp. and cf. Meristodonoides sp.), this assemblage is remarkable in that there are only very few Mesozoic hybodontiform assemblages with more large-toothed genera or even species. Comparisons with other European Late Jurassic hybodontiform-bearing localities demonstrate fairly homogenous distribution patterns characterized by large-bodied epipelagic forms of high dispersal ability. This is in stark contrast to post-Jurassic hybodontiform associations, which are dominated by smaller species that were predominantly bound to marginal marine and continental waters, suggesting a major reorganization of chondrichthyan communities during the Early Cretaceous.
Entropy Method of Road Safety Management: Case Study of the Russian Federation
Authors: Petrov Artur I.
Published: January 2022

Within the framework of this paper, the author’s entropy method of road safety management in large-sized systems is considered. The road safety management system in the Russian Federation, the largest country in the world, was selected for this case study. The purpose of the article is to present the opportunities and methodology of the use of quantitative assessments of the orderliness of the road accident rate formation process in regional transport systems for road safety management. Orderliness, in other words, systemic anti-chaos, can be quantified using the C. Shannon informational entropy H. The article consists of the results of the issue’s state analysis; methodology of assessment of the orderliness of the road accident rate formation process based on the using of the cause-and-effect chain; entropic method of the road safety management in large-scale systems, in particular, the algorithm of management of regional road safety in Russia taking into account the level of its entropic orderliness; and examples of the quantitative evaluation of the orderliness of regional road safety provision systems in Russia. The key results of the research are spatio-temporal patterns of the change of the orderliness of the road safety provision systems in the Russian Federation in 2004–2020. Based on the results, conclusions and recommendations about the practical application of the entropic method of road safety management in large federal states with complex administrative structures were formulated. These results give an idea of the possibilities of the usage of entropic approaches in road safety management to assess the orderliness of the regional transport systems and the advantages of the entropic method over other managerial methods.
The Classical-Quantum Dichotomy from the Perspective of the Process Algebra
Authors: Sulis William
Published: January 2022

The classical-quantum dichotomy is analyzed from the perspective of the Process Algebra approach, which views fundamental phenomena through the lens of complex systems theory and Whitehead’s process theory. Broadly, the dichotomy can be framed in terms of differences in ontology (phenomena and their behavior) and differences in epistemology (theoretical languages used in their description). The Process Algebra posits a reality, generated by processes, whose fundamental characteristics include becoming, generativity, transience, locality, and contextuality. From this perspective, the classical-quantum dichotomy appears to be a false dichotomy—it arises because of stereotyped, strawman-like depictions of what it means to be classical or quantum. A more careful examination reveals that reality is unitary, that whether a system behaves in a quantum or classical manner depends upon its particularities, in particular, whether it is complex or not, and how information flows govern its dynamics.
Clinical Profile and Acute-Phase Management Modalities of Pediatric Hand Burn: A Retrospective Study
Authors: Gurbuz Kayhan , Demir Mete
Published: January 2022

Although the hands constitute approximately 5% of the total body surface area (TBSA), the sequelae and subsequent functional outcomes following hand burns (HBs) significantly impact the quality of life for affected patients. HBs, which frequently accompany severe burns and are often neglected, deserve additional attention in the management of burns of this anatomical region, as they are responsible for a majority of postburn morbidity. In addition, many questions remain unanswered in almost every aspect of HB management. Moreover, recent articles suggest that the primary issue of optimal timing concerning skin closure for HBs, which seemed well answered, has been questioned, and even this fundamental question may require further investigation. Appropriate initial management of HBs commencing from the acute phase in children remains of great importance in optimizing functional outcomes and minimizing long-term scar formation. In this context, our primary purpose in this retrospective cohort study was to present the epidemiological characteristics of HBs in children as a whole and to discuss the incidence and mechanisms, in addition to the outcomes of superficial and deep HB acute-phase management modalities. During the 5-year study period, HBs were detected in 27% (n = 422) of 1580 hospitalized pediatric burn patients in the Adana Faculty of Medicine-University of Health Sciences (AFM-UHS) Burn Center. Movement and functional status of the hands were evaluated with a simple qualitative staging system adapted from the original scoring tools used by Stiefel et al., and Sheridan et al. Good, moderate, and poor scores in the study were graded as Category A, Category B, and Category C, respectively. According to the hand movement and function assessment categorization, 84% of the cases were observed as Category-A who had good/normal regular movements/functions of the hands/fingers, followed by Category-B and -C with percentages of 15 and 1, respectively, during the 5.8 ± 3.4 month follow-up period.
The Quality of Training Staff for the Digital Economy of Russia within the Framework of STEAM Education: Problems and Solutions in the Context of Distance Learning
Authors: Anisimova Tatyana , Sabirova Fairuza , Shatunova Olga , Bochkareva Tatyana , Vasilev Vladimir
Published: January 2022

The purpose of this study is to analyze the problems of quality training of personnel for the digital economy of Russia during the pandemic within the framework of STEAM education and to identify their solutions with the help of the most effective distance learning tools. The research is based on a survey of 138 respondents (students of the Department of Mathematics and Natural Sciences of the Yelabuga Institute of the Kazan Federal University), who have mastered professional competencies in a distance learning format during the pandemic. The results of the survey confirmed the conclusion that distance learning tools such as Moodle, Google Classroom, and Microsoft Teams have shown their effectiveness and can be successfully used not only in the context of extreme situations, for example, a pandemic, but also as elements of blended learning while bringing variety to the forms of learning, and thereby strengthening the process of training STEAM education specialists. The scientific novelty of the study lies in a deep analysis of the distance learning tools used for training specialists for the digital economy of Russia, namely STEAM education specialists, based on the collection of information from students during the period of transformational changes in the pedagogical education system.
Does Energy Community Membership Change Sustainable Attitudes and Behavioral Patterns? Empirical Evidence from Community Wind Energy in Germany
Authors: Radtke Jörg , Yildiz Özgür , Roth Lucas
Published: January 2022

Community energy is seen as a helping hand for local, decentralized energy transition. Besides the main goal of supporting the community-friendly and socially acceptable development of renewable energies, the hope is also that a pro-environmental influence on sustainability behavior will be triggered when joining a community energy project. An analysis of a survey among 16 community energy projects in Germany, with 565 completed questionnaires, shows that a certain part of the members pays more attention to their energy behavior and develop a more positive attitude towards a decentralized energy transition and citizen participation after joining the community energy project. Therefore, we can empirically support that climate protection projects, such as community energy, influence pro-environmental attitudes and behavior, but this does not apply equally to all population groups. Members with higher income and stronger interest in returns are less likely to change their behavior. Based on these findings, we recommend the development of community energy policies that are more responsive to differences in social structure and address both privileged and underprivileged groups in a sophisticated way using specific offers and modes of involvement within the associations.
A Data-Centric Machine Learning Methodology: Application on Predictive Maintenance of Wind Turbines
Authors: Garan Maryna , Tidriri Khaoula , Kovalenko Iaroslav
Published: January 2022

Nowadays, the energy sector is experiencing a profound transition. Among all renewable energy sources, wind energy is the most developed technology across the world. To ensure the profitability of wind turbines, it is essential to develop predictive maintenance strategies that will optimize energy production while preventing unexpected downtimes. With the huge amount of data collected every day, machine learning is seen as a key enabling approach for predictive maintenance of wind turbines. However, most of the effort is put into the optimization of the model architectures and its parameters, whereas data-related aspects are often neglected. The goal of this paper is to contribute to a better understanding of wind turbines through a data-centric machine learning methodology. In particular, we focus on the optimization of data preprocessing and feature selection steps of the machine learning pipeline. The proposed methodology is used to detect failures affecting five components on a wind farm composed of five turbines. Despite the simplicity of the used machine learning model (a decision tree), the methodology outperformed model-centric approach by improving the prediction of the remaining useful life of the wind farm, making it more reliable and contributing to the global efforts towards tackling climate change.
Nondestructive Testing of the Integrity of Solid Oxide Fuel Cell Stack Elements by Ultrasound and Thermographic Techniques
Authors: Netzelmann Udo , Mross Andrea , Waschkies Thomas , Weber Dietmar , Toma Ewald , Neurohr Holger
Published: January 2022

Single planar fuel cell elements consisting of metallic interconnectors that are bonded and sealed by a thin glass solder layer form the core of a solid oxide fuel cell. For reliable operation, the bonding layer has to adhere well and must be without voids or foreign material inclusions, which might cause gas leakage, electrical shorts or mechanical weakening and structural failure. Nondestructive testing (NDT) by the high-frequency ultrasound in immersion technique and by air-coupled ultrasound was optimized to find such defects. Another technique was flash light excited thermography for detection of voids. The NDT techniques used are complementary to each other, as they are based on different physical principles. Voids and small steel platelets of different sizes were prepared in the glass solder layer before the high-temperature bonding process and then monitored by the NDT techniques through the interconnector plates. Two selected NDT techniques were then validated in a probability of detection (POD) study. The study resulted in detection limits for the two main types of defects. As a step towards production testing, a demonstrator was built combining testing by air-coupled ultrasound and that by flash thermography. During the testing steps, the cell elements were handled by a collaborative robot.
Demonstration of 5G Solutions for Smart Energy Grids of the Future: A Perspective of the Smart5Grid Project
Authors: Porcu Daniele , Castro Sonia , Otura Borja , Encinar Paula , Chochliouros Ioannis , Ciornei Irina , Hadjidemetriou Lenos , Ellinas Georgios , Santiago Rita , Grigoriou Elisavet , Antonopoulos Angelos , Cadenelli Nicola , di Pietro Nicola , Betzler August , Prieto Inmaculada , Battista Fabrizio , Brodimas Dimitrios , Rumenova Ralitsa , Bachoumis Athanasios
Published: January 2022

As the complexity of electric systems increases, so does the required effort for the monitoring and management of grid operations. To solve grid performance issues, smart grids require the exchange of higher volumes of data, high availability of the telecommunication infrastructure, and very low latency. The fifth generation (5G) mobile network seems to be the most promising technology to support such requirements, allowing utilities to have dedicated virtual slices of network resources to maximize the service availability in case of network congestions. Regarding this evolving scenario, this work presents the Smart5Grid project vision on how 5G can support the energy vertical industry for the fast deployment of innovative digital services. Specifically, this work introduces the concept of network applications (NetApps), a new paradigm of virtualization that are envisioned to facilitate the creation of a new market for information technology (IT), small and medium enterprises (SMEs), and startups. This concept, and the open architecture that facilitates its implementation, is showcased by four real-life 5G-enabled demonstrators: (1) automatic fault detection in a medium voltage (MV) grid in Italy, (2) real-time safety monitoring for operators in high voltage (HV) substations in Spain, (3) remote distributed energy resources (DER) monitoring in Bulgaria, and (4) wide area monitoring in a cross-border scenario between Greece and Bulgaria.
Raspberry Pi Design and Hardware Implementation of Fuzzy-PI Controller for Three-Phase Grid-Connected Inverter
Authors: Mostafa Sameh , Zekry Abdelhalim , Youssef Ayman , Anis Wagdi Refaat
Published: January 2022

A photovoltaic system is one of the major sources of renewable energy. The grid-connected inverter controllers play an important role in the conversion and transmission of solar energy. Therefore, they must be improved to meet the demands for grid interconnection. This article introduces the design and hardware implementation of the intelligent fuzzy-PI controller of the inverter part of the grid-connected photovoltaic system. First, the paper discusses the design of the three-phase grid-connected fuzzy-PI controller. Next, the paper describes the implementation of a Matlab graphical user interface (GUI) to design any grid-connected inverter and size the photovoltaic systems. The code generation of the fuzzy-PI controller of the system is accomplished by using Matlab Simulink simulation software. The hardware components of the PV system are implemented experimentally. In the hardware implementation, a 70 W prototype is realized to test the functionality of the controller, such that one can develop a realistic controller without taking risks or falling into security concerns in the case of performing experiments on high-power systems. The prototype proves that the controller model can be directly transformed from Simulink to the control device. It also shows that the fuzzy-PI controller is working properly in the 70-watt prototype. The achieved performance parameters of the proposed fuzzy-PI controller are satisfactory. The proposed method to design and implement the fuzzy-PI controller does not require complicated programming, where a Matlab coder is proposed to transform the Simulink controller into C code that can be directly utilized as a software control program loaded in the microcontrollers embedded in the hardware of the controller. The main result is that the fuzzy-PI controller for the three-phase grid-connected systems can be implemented using low-cost reconfigurable microcontrollers.