bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the Biocidal Performance of Multi-Functional Resin/Copper Nanocomposites with Superior Mechanical Response in SLA 3D Printing
Authors: Vidakis Nectarios , Petousis Markos , Velidakis Emmanuel , Mountakis Nikolaos , Tsikritzis Dimitris , Gkagkanatsiou Aikaterini , Kanellopoulou Sotiria
Published: January 2022

Metals, such as silver, gold, and copper are known for their biocidal properties, mimicking the host defense peptides (HDPs) of the immune system. Developing materials with such properties has great importance in medicine, especially when combined with 3D printing technology, which is an additional asset for various applications. In this work, copper nanoparticles were used as filler in stereolithography (SLA) ultraviolet (UV) cured commercial resin to induce such biocidal properties in the material. The nanocomposites developed featured enhanced mechanical responses when compared with the neat material. The prepared nanocomposites were employed to manufacture specimens with the SLA process, to be tested for their mechanical response according to international standards. The process followed was evaluated with Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), energy-dispersive X-ray spectroscopy (EDS), and thermogravimetric analysis (TGA). The antibacterial activity of the fabricated nanocomposites was evaluated using the agar-well diffusion method. Results showed enhanced mechanical performance of approximately 33.7% in the tensile tests for the nanocomposites filled with 1.0 wt.%. ratios, when compared to the neat matrix material, while this loading showed sufficient antibacterial performance when compared to lower filler loadings, providing an added value for the fabrication of effective nanocomposites in medical applications with the SLA process.
Blinding in tDCS Studies: Correct End-of-Study Guess Does Not Moderate the Effects on Associative and Working Memory
Authors: Stanković Marija , Živanović Marko , Bjekić Jovana , Filipović Saša R.
Published: January 2022

Transcranial direct current stimulation (tDCS) has become a valuable tool in cognitive neuroscience research as it enables causal inferences about neural underpinnings of cognition. However, studies using tDCS to modulate cognitive functions often yield inconsistent findings. Hence, there is an increasing interest in factors that may moderate the effects, one of which is the participants’ beliefs of the tDCS condition (i.e., real or sham) they received. Namely, whether participants’ correct guessing of sham condition may lead to false-positive tDCS effects. In this study, we aimed to explore if participants’ beliefs about received stimulation type (i.e., the success of blinding) impacted their task performance in tDCS experiments on associative (AM) and working memory (WM). We analyzed data from four within-subject, sham-controlled tDCS memory experiments (N = 83) to check if the correct end-of-study guess of sham condition moderated tDCS effects. We found no evidence that sham guessing moderated post-tDCS memory performance in experiments in which tDCS effects were observed as well as in experiments that showed null effects of tDCS. The results suggest that the correct sham guessing (i.e., placebo-like effect) is unlikely to influence the results in tDCS memory experiments. We discuss the results in light of the growing debate about the relevance and effectiveness of blinding in brain stimulation research.
Correction: Petry-Schmelzer et al. Selecting the Most Effective DBS Contact in Essential Tremor Patients Based on Individual Tractography. Brain Sci. 2020, 10, 1015
Authors: Petry-Schmelzer Jan Niklas , Dembek Till A. , Steffen Julia K. , Jergas Hannah , Dafsari Haidar S. , Fink Gereon R. , Visser-Vandewalle Veerle , Barbe Michael T.
Published: January 2022

The authors wish to make the following correction to [...]
Test–Retest Reliability of Synchrony and Metastability in Resting State fMRI
Authors: Yang Lan , Wei Jing , Li Ying , Wang Bin , Guo Hao , Yang Yanli , Xiang Jie
Published: January 2022

In recent years, interest has been growing in dynamic characteristic of brain signals from resting-state functional magnetic resonance imaging (rs-fMRI). Synchrony and metastability, as neurodynamic indexes, are considered as one of methods for analyzing dynamic characteristics. Although much research has studied the analysis of neurodynamic indices, few have investigated its reliability. In this paper, the datasets from the Human Connectome Project have been used to explore the test–retest reliabilities of synchrony and metastability from multiple angles through intra-class correlation (ICC). The results showed that both of these indexes had fair test–retest reliability, but they are strongly affected by the field strength, the spatial resolution, and scanning interval, less affected by the temporal resolution. Denoising processing can help improve their ICC values. In addition, the reliability of neurodynamic indexes was affected by the node definition strategy, but these effects were not apparent. In particular, by comparing the test–retest reliability of different resting-state networks, we found that synchrony of different networks was basically stable, but the metastability varied considerably. Among these, DMN and LIM had a relatively higher test–retest reliability of metastability than other networks. This paper provides a methodological reference for exploring the brain dynamic neural activity by using synchrony and metastability in fMRI signals.
Evidence from ERP and Eye Movements as Markers of Language Dysfunction in Dyslexia
Authors: Premeti Aikaterini , Bucci Maria Pia , Isel Frédéric
Published: January 2022

Developmental dyslexia is a complex reading disorder involving genetic and environmental factors. After more than a century of research, its etiology remains debated. Two hypotheses are often put forward by scholars to account for the causes of dyslexia. The most common one, the linguistic hypothesis, postulates that dyslexia is due to poor phonological awareness. The alternative hypothesis considers that dyslexia is caused by visual-attentional deficits and abnormal eye movement patterns. This article reviews a series of selected event-related brain potential (ERP) and eye movement studies on the reading ability of dyslexic individuals to provide an informed state of knowledge on the etiology of dyslexia. Our purpose is to show that the two abovementioned hypotheses are not necessarily mutually exclusive, and that dyslexia should rather be considered as a multifactorial deficit.
Carbon Nanomaterials for Theranostic Use
Authors: Kościk Izabela , Jankowski Daniel , Jagusiak Anna
Published: January 2022

Based on statistics from the National Cancer Institute in the US, the rate of new cases of cancer is 442.4 per 100,000 men and women per year, and more than one-third do not survive the disease. Cancer diagnosis and treatment are the most important challenges in modern medicine. The majority of cancer cases are diagnosed at an early stage. However, the possibility of simultaneous diagnosis and application of therapy (theranostics) will allow for acceleration and effectiveness of treatment. Conventional chemotherapy is not effective in reducing the chemoresistance and progression of various types of cancer. In addition, it causes side effects, which are mainly a result of incorrect drug distribution. Hence, new therapies are being explored as well as new drug delivery strategies. In this regard, nanotechnology has shown promise in the targeted delivery of therapeutics to cancer cells. This review looks at the latest advances in drug delivery-based diagnosis and therapy. Drug delivery nanosystems made of various types of carbon (graphene, fullerenes, and carbon nanotubes) are discussed. Their chemical properties, advantages, and disadvantages are explored, and these systems are compared with each other.
The X-ray, Raman and TEM Signatures of Cellulose-Derived Carbons Explained
Authors: Mubari Petros Kasaira , Beguerie Théotime , Monthioux Marc , Weiss-Hortala Elsa , Nzihou Ange , Puech Pascal
Published: January 2022

Structural properties of carbonized cellulose were explored to conjugate the outcomes from various characterization techniques, namely X-ray diffraction (XRD), Raman spectroscopy, and high-resolution transmission electron microscopy. All these techniques have evidenced the formation of graphene stacks with a size distribution. Cellulose carbonized at 1000 and 1800 °C at a heating rate of 2 °C/min showed meaningful differences in Raman spectroscopy, whereas in XRD, the differences were not well pronounced, which implies that the crystallite sizes calculated by each technique have different significations. In the XRD patterns, the origin of a specific feature at a low scattering angle commonly reported in the literature but poorly explained so far, was identified. The different approaches used in this study were congruous in explaining the observations that were made on the cellulose-derived carbon samples. The remnants of the basic structural unit (BSU) are developed during primary carbonization. Small graphene-based crystallites inherited from the BSUs, which formerly developed during primary carbonization, were found to coexist with larger ones. Even if the three techniques give information on the average size of graphenic domains, they do not see the same characteristics of the domains; hence, they are not identical, nor contradictory but complementary. The arguments developed in the work to explain which characteristics are deduced from the signal obtained by each of the three characterization techniques relate to physics phenomena; hence, they are quite general and, therefore, are valid for all kind of graphenic materials.
The Systemic Inflammatory Response Identifies Patients with Adverse Clinical Outcome from Immunotherapy in Hepatocellular Carcinoma
Authors: Muhammed Ambreen , Fulgenzi Claudia Angela Maria , Dharmapuri Sirish , Pinter Matthias , Balcar Lorenz , Scheiner Bernhard , Marron Thomas U. , Jun Tomi , Saeed Anwaar , Hildebrand Hannah , Muzaffar Mahvish , Navaid Musharraf , Naqash Abdul Rafeh , Gampa Anuhya , Ozbek Umut , Lin Junk-Yi , Perone Ylenia , Vincenzi Bruno , Silletta Marianna , Pillai Anjana , Wang Yinghong , Khan Uqba , Huang Yi-Hsiang , Bettinger Dominik , Abugabal Yehia I. , Kaseb Ahmed , Pressiani Tiziana , Personeni Nicola , Rimassa Lorenza , Nishida Naoshi , Di Tommaso Luca , Kudo Masatoshi , Vogel Arndt , Mauri Francesco A. , Cortellini Alessio , Sharma Rohini , D’Alessio Antonio , Ang Celina , Pinato David J.
Published: January 2022

Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic responses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.
Correlation Analysis of Protein Expression of 10 HDAC/Sirtuin Isoenzymes with Sensitivities of 23 Anticancer Drugs in 17 Cancer Cell Lines and Potentiation of Drug Activity by Co-Treatment with HDAC Inhibitors
Authors: Behnisch-Cornwell Steven , Grathwol Christoph W. , Schulig Lukas , Voigt Anika , Baecker Daniel , Link Andreas , Bednarski Patrick J.
Published: January 2022

Inhibiting the activity of histone deacetylase (HDAC) is an ongoing strategy in anticancer therapy. However, to our knowledge, the relationships between the expression of HDAC proteins and the antitumor drug sensitivity of cancer cells have not been studied until now. In the current work, we investigated the relative expression profiles of 10 HDAC isoenzymes comprising the classes I–III (HDAC1/2/4/6; Sirt1/2/3/5/6/7) in a panel of 17 cancer cell lines, including the breast, cervix, oesophageal, lung, oral squamous, pancreas, as well as urinary bladder carcinoma cells. Correlations between the data of mRNA expression for these enzymes obtained from the National Cancer Institute (NCI) 60 cancer cell line program were also examined. Next, we performed univariate analysis between the expression patterns of HDAC/Sirt isoenzymes with the sensitivity of a 16 cell panel of cancer cell lines towards several antitumor drugs. In a univariate correlation analysis, we found a strong relation between Sirt2 expression and cytotoxicity caused by busulfan, etoposide, and hydroxyurea. Moreover, it was identified that Sirt5 correlates with the effects exerted by oxaliplatin or topotecan, as well as between HDAC4 expression and these two drugs. Correlations between the data of mRNA expression for enzymes with the potencies of the same anticancer agents obtained from the NCI 60 cancer cell line program were also found, but none were the same as those we found with our protein expression data. Additionally, we report here the effects upon combination of the approved HDAC inhibitor vorinostat and one other known inhibitor trichostatin A as well as newer hetero-stilbene and diazeno based sirtuin inhibitors on the potency of cisplatin, lomustine, and topotecan. For these three anticancer drugs, we found a significantly enhanced cytotoxicity when co-incubated with HDAC inhibitors, demonstrating a potentially beneficial influence of HDAC inhibition on anticancer drug treatment.
CNV Hotspots in Testicular Seminoma Tissue and Seminal Plasma
Authors: Raos Dora , Abramović Irena , Tomić Miroslav , Vrtarić Alen , Kuliš Tomislav , Ćorić Marijana , Ulamec Monika , Katušić Bojanac Ana , Ježek Davor , Sinčić Nino
Published: January 2022

Seminoma (SE) is the most frequent type of testicular tumour, affecting predominantly young men. Early detection and diagnosis of SE could significantly improve life quality and reproductive health after diagnosis and treatment. Copy number variation (CNV) has already been associated with various cancers as well as SE. In this study, we selected four genes (MAGEC2, NANOG, RASSF1A, and KITLG) for CNV analysis in genomic DNA (gDNA), which are located on chromosomes susceptible to gains, and whose aberrant expression was already detected in SE. Furthermore, CNV was analysed in cell-free DNA (cfDNA) from seminal plasma. Analysis was performed by droplet digital polymerase chain reaction (ddPCR) on gDNA from SE and nonmalignant testicular tissue. Seminal plasma cfDNA from SE patients before and after surgery was analysed, as well as from healthy volunteers. The CNV hotspot in gDNA from SE tissue was detected for the first time in all analysed genes, and for two genes, NANOG and KITLG it was reflected in cfDNA from seminal plasma. Although clinical value is yet to be determined, presented data emphasize a potential use of CNV as a potential SE biomarker from a liquid biopsy.
Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer
Authors: Wallace-Povirk Adrianne , Hou Zhanjun , Nayeen Md. Junayed , Gangjee Aleem , Matherly Larry H.
Published: January 2022

New therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. To identify new approaches for targeting EOC, metabolic vulnerabilities must be discovered and strategies for the selective delivery of therapeutic agents must be established. Folate receptor (FR) α and the proton-coupled folate transporter (PCFT) are expressed in the majority of EOCs. FRβ is expressed on tumor-associated macrophages, a major infiltrating immune population in EOC. One-carbon (C1) metabolism is partitioned between the cytosol and mitochondria and is important for the synthesis of nucleotides, amino acids, glutathione, and other critical metabolites. Novel inhibitors are being developed with the potential for therapeutic targeting of tumors via FRs and the PCFT, as well as for inhibiting C1 metabolism. In this review, we summarize these exciting new developments in targeted therapies for both tumors and the tumor microenvironment in EOC.
A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy
Authors: Guo Feifei , Estévez-Vázquez Olga , Benedé-Ubieto Raquel , Maya-Miles Douglas , Zheng Kang , Gallego-Durán Rocío , Rojas Ángela , Ampuero Javier , Romero-Gómez Manuel , Philip Kaye , Egbuniwe Isioma U. , Chen Chaobo , Simon Jorge , Delgado Teresa C. , Martínez-Chantar María Luz , Sun Jie , Reissing Johanna , Bruns Tony , Lamas-Paz Arantza , Moral Manuel Gómez del , Woitok Marius Maximilian , Vaquero Javier , Regueiro José R. , Liedtke Christian , Trautwein Christian , Bañares Rafael , Cubero Francisco Javier , Nevzorova Yulia A.
Published: January 2022

Background: Metabolic-associated fatty liver disease (MAFLD) has risen as one of the leading etiologies for hepatocellular carcinoma (HCC). Oncogenes have been suggested to be responsible for the high risk of MAFLD-related HCC. We analyzed the impact of the proto-oncogene c-MYC in the development of human and murine MAFLD and MAFLD-associated HCC. Methods: alb-myctg mice were studied at baseline conditions and after administration of Western diet (WD) in comparison to WT littermates. c-MYC expression was analyzed in biopsies of patients with MAFLD and MAFLD-associated HCC by immunohistochemistry. Results: Mild obesity, spontaneous hyperlipidaemia, glucose intolerance and insulin resistance were characteristic of 36-week-old alb-myctg mice. Middle-aged alb-myctg exhibited liver steatosis and increased triglyceride content. Liver injury and inflammation were associated with elevated ALT, an upregulation of ER-stress response and increased ROS production, collagen deposition and compensatory proliferation. At 52 weeks, 20% of transgenic mice developed HCC. WD feeding exacerbated metabolic abnormalities, steatohepatitis, fibrogenesis and tumor prevalence. Therapeutic use of metformin partly attenuated the spontaneous MAFLD phenotype of alb-myctg mice. Importantly, upregulation and nuclear localization of c-MYC were characteristic of patients with MAFLD and MAFLD-related HCC. Conclusions: A novel function of c-MYC in MAFLD progression was identified opening new avenues for preventative strategies.
The Emerging Role of PIWI-Interacting RNAs (piRNAs) in Gastrointestinal Cancers: An Updated Perspective
Authors: Riquelme Ismael , Pérez-Moreno Pablo , Letelier Pablo , Brebi Priscilla , Roa Juan Carlos
Published: January 2022

Gastrointestinal (GI) cancers produce ~3.4 million related deaths worldwide, comprising 35% of all cancer-related deaths. The high mortality among GI cancers is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not adequately guide patient management, thereby new and more reliable biomarkers and therapeutic targets are still needed for these diseases. RNA-seq technology has allowed the discovery of new types of RNA transcripts including PIWI-interacting RNAs (piRNAs), which have particular characteristics that enable these molecules to act via diverse molecular mechanisms for regulating gene expression. Cumulative evidence has described the potential role of piRNAs in the development of several tumor types as a likely explanation for certain genomic abnormalities and signaling pathways’ deregulations observed in cancer. In addition, these piRNAs might be also proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in malignancies. This review describes important topics about piRNAs including their molecular characteristics, biosynthesis processes, gene expression silencing mechanisms, and the manner in which these transcripts have been studied in samples and cell lines of GI cancers to elucidate their implications in these diseases. Moreover, this article discusses the potential clinical usefulness of piRNAs as biomarkers and therapeutic targets in GI cancers.
CTCF Expression and Dynamic Motif Accessibility Modulates Epithelial–Mesenchymal Gene Expression
Authors: Johnson Kelsey S. , Hussein Shaimaa , Chakraborty Priyanka , Muruganantham Arvind , Mikhail Sheridan , Gonzalez Giovanny , Song Shuxuan , Jolly Mohit Kumar , Toneff Michael J. , Benton Mary Lauren , Lin Yin C. , Taube Joseph H.
Published: January 2022

Epithelial–mesenchymal transition (EMT) and its reversal, mesenchymal–epithelial transition (MET) drive tissue reorganization critical for early development. In carcinomas, processing through EMT, MET, or partial states promotes migration, invasion, dormancy, and metastatic colonization. As a reversible process, EMT is inherently regulated at epigenetic and epigenomic levels. To understand the epigenomic nature of reversible EMT and its partial states, we characterized chromatin accessibility dynamics, transcriptomic output, protein expression, and cellular phenotypes during stepwise reversible EMT. We find that the chromatin insulating protein machinery, including CTCF, is suppressed and re-expressed, coincident with broad alterations in chromatin accessibility, during EMT/MET, and is lower in triple-negative breast cancer cell lines with EMT features. Through an analysis of chromatin accessibility using ATAC-seq, we identify that early phases of EMT are characterized by enrichment for AP-1 family member binding motifs, but also by a diminished enrichment for CTCF binding motifs. Through a loss-of-function analysis, we demonstrate that the suppression of CTCF alters cellular plasticity, strengthening the epithelial phenotype via the upregulation of epithelial markers E-cadherin/CDH1 and downregulation of N-cadherin/CDH2. Conversely, the upregulation of CTCF leads to the upregulation of EMT gene expression and an increase in mesenchymal traits. These findings are indicative of a role of CTCF in regulating epithelial–mesenchymal plasticity and gene expression.
Phototheranostics of Cervical Neoplasms with Chlorin e6 Photosensitizer
Authors: Gilyadova Aida , Ishchenko Anton , Shiryaev Artem , Alekseeva Polina , Efendiev Kanamat , Karpova Radmila , Loshchenov Maxim , Loschenov Victor , Reshetov Igor
Published: January 2022

(1) Purpose: Improving the treatment effectiveness of intraepithelial neoplasia of the cervix associated with human papillomavirus infection, based on the application of the method of photodynamic therapy with simultaneous laser excitation of fluorescence to clarify the boundaries of cervical neoplasms. (2) Methods: Examination and treatment of 52 patients aged 22 to 53 years with morphologically and cytologically confirmed mild to severe intraepithelial cervix neoplasia, preinvasive, micro-invasive, and squamous cell cervix carcinoma. All patients were carriers of human papillomavirus infection. The patients underwent photodynamic therapy with simultaneous laser excitation of fluorescence. The combined use of video and spectral fluorescence diagnostics for cervical neoplasms made it possible to control the photodynamic therapy process at all stages of the procedure. Evaluation of the photodynamic therapy of intraepithelial cervical neoplasms was carried out with colposcopic examination, cytological conclusion, and morphological verification of the biopsy material after the photodynamic therapy course. The success of human papillomavirus therapy was assessed based on the results of the polymerase chain reaction. (3) Results. The possibility of simultaneous spectral fluorescence diagnostics and photodynamic therapy using a laser source with a wavelength of 660 nm has been established, making it possible to assess the fluorescence index in real-time and control the photobleaching of photosensitizers in the irradiated area. The treatment of all 52 patients was successful after the first photodynamic therapy procedure. According to the PCR test of the discharge from the cervical canal, the previously identified HPV types were not observed in 48 patients. Previously identified HPV types were absent after repeated PDT in four patients (CIN III (n = 2), CIS (n = 2)). In 80.8% of patients, regression of the lesion was noted. (4) Conclusions. The high efficiency of photodynamic therapy with intravenous photosensitizer administration of chlorin e6 has been demonstrated both in relation to eradication therapy of human papillomavirus and in relation to the treatment of intraepithelial lesions of the cervix.
Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study
Authors: Tantari Matteo , Bogliolo Stefano , Morotti Matteo , Balaya Vincent , Bouttitie Florent , Buenerd Annie , Magaud Laurent , Lecuru Fabrice , Guani Benedetta , Mathevet Patrice ,   on behalf of the SENTICOL Group
Published: January 2022

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.
Synergistic Action of Immunotherapy and Nanotherapy against Cancer Patients Infected with SARS-CoV-2 and the Use of Artificial Intelligence
Authors: Gupta Tanvi , Debele Tilahun Ayane , Wei Yu-Feng , Gupta Anish , Murtaza Mohd , Su Wen-Pin
Published: January 2022

Since 2019, the SARS-CoV-2 pandemic has caused a huge chaos throughout the world and the major threat has been possessed by the immune-compromised individuals involving the cancer patients; their weakened immune response makes them vulnerable and susceptible to the virus. The oncologists as well as their patients are facing many problems for their treatment sessions as they need to postpone their surgery, chemotherapy, or radiotherapy. The approach that could be adopted especially for the cancer patients is the amalgamation of immunotherapy and nanotherapy which can reduce the burden on the healthcare at this peak time of the infection. There is also a need to predict or analyze the data of cancer patients who are at a severe risk of being exposed to an infection in order to reduce the mortality rate. The use of artificial intelligence (AI) could be incorporated where the real time data will be available to the physicians according to the different patient’s clinical characteristics and their past treatments. With this data, it will become easier for them to modify or replace the treatment to increase the efficacy against the infection. The combination of an immunotherapy and nanotherapy will be targeted to treat the cancer patients diagnosed with SARS-CoV-2 and the AI will act as icing on the cake to monitor, predict and analyze the data of the patients to improve the treatment regime for the most vulnerable patients.
FoxO3a Inhibits Tamoxifen-Resistant Breast Cancer Progression by Inducing Integrin α5 Expression
Authors: Ricci Elena , Fava Mariarosa , Rizza Pietro , Pellegrino Michele , Bonofiglio Daniela , Casaburi Ivan , Lanzino Marilena , Giordano Cinzia , Bruno Rosalinda , Sirianni Rosa , Barone Ines , Sisci Diego , Morelli Catia
Published: January 2022

Resistance to endocrine therapy is still a major clinical challenge in the management of estrogen receptor α-positive (ERα+) breast cancer (BC). Here, the role of the Forkhead box class O (FoxO)3a transcription factor in tumor progression has been evaluated in tamoxifen-resistant BC cells (TamR), expressing lower levels of FoxO3a compared to sensitive ones. FoxO3a re-expression reduces TamR motility (wound-healing and transmigration assays) and invasiveness (matrigel transwell invasion assays) through the mRNA (qRT-PCR) and protein (Western blot) induction of the integrin α5 subunit of the α5β1 fibronectin receptor, a well-known membrane heterodimer controlling cell adhesion and signaling. The induction occurs through FoxO3a binding to a specific Forkhead responsive core sequence located on the integrin α5 promoter (cloning, luciferase, and ChIP assays). Moreover, FoxO3a failed to inhibit migration and invasion in integrin α5 silenced (siRNA) cells, demonstrating integrin α5 involvement in both processes. Finally, using large-scale gene expression data sets, a strong positive correlation between FoxO3a and integrin α5 in ERα+, but not in ER-negative (ERα−), BC patients emerged. Altogether, our data show how the oncosuppressor FoxO3a, by increasing the expression of its novel transcriptional target integrin α5, reverts the phenotype of endocrine-resistant BC toward a lower aggressiveness.
Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results
Authors: Foti Pietro Valerio , Inì Corrado , Broggi Giuseppe , Farina Renato , Palmucci Stefano , Spatola Corrado , Liardo Rocco Luca Emanuele , Milazzotto Roberto , Raffaele Luigi , Salamone Vincenzo , Caltabiano Rosario , Puzzo Lidia , Russo Andrea , Reibaldi Michele , Longo Antonio , Vigneri Paolo , Venturini Massimo , Giurazza Francesco , Avitabile Teresio , Basile Antonio
Published: January 2022

Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.
Microsatellite Instability, Epstein–Barr Virus, and Programmed Cell Death Ligand 1 as Predictive Markers for Immunotherapy in Gastric Cancer
Authors: Yu Hung-Yuan , Li Chung-Pin , Huang Yi-Hsiang , Hsu Shao-Jung , Wang Yen-Po , Hsieh Yun-Cheng , Fang Wen-Liang , Huang Kuo-Hung , Li Anna Fen-Yau , Lee Rheun-Chuan , Lee Kang-Lung , Wu Yuan-Hung , Lai I-Chun , Yang Wan-Chin , Hung Yi-Ping , Wang Yu-Chao , Chen Shu-Hui , Chen Ming-Huang , Chao Yee
Published: January 2022

Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers—microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein–Barr encoding region (EBER)—were analyzed. Eight patients had MSI-H, five patients had EBER, 29 patients had CPS ≥ 1, and 20 patients had no biomarker. The overall response rates (ORRs) of the MSI-H, EBER, PD-L1 CPS ≥ 1, and all-negative group were 75%, 60%, 44.8%, and 15%, respectively. Compared with that of the all-negative group, progression-free survival (PFS) was better in the MSI-H (p = 0.018), CPS ≥ 5 (p = 0.012), and CPS ≥ 10 (p = 0.006) groups, but not in the EBER (p = 0.2) and CPS ≥ 1 groups (p = 0.35). Ten patients had combined biomarkers, CPS ≥ 1 with either MSI-H or EBER. The ORRs were 66.7% for CPS ≥ 1 and MSI-H and 75% for CPS ≥ 1 and EBER. PFS was better in patients with combined biomarkers (p = 0.01). MSI-H, EBER, and CPS are useful biomarkers for predicting the efficacy of immunotherapy.
Arterial Administration of DNA Crosslinking Agents with Restraint of Homologous Recombination Repair by Intravenous Low-Dose Gemcitabine Is Effective for Locally Advanced Pancreatic Cancer
Authors: Mori Hiromu , Tanoue Shuichi , Takaji Ryo , Ueda Shinya , Okahara Mika , Ueda Saori Sugi
Published: January 2022

(1) Background: Pretreatment by Rad51-inhibitory substances such as gemcitabine followed by arterial chemotherapy using antineoplastic agents causing DNA crosslink might be more beneficial for patients with locally advanced pancreatic cancers than conventional treatments. The efficacy of arterial administration of DNA crosslinking agents with pretreatment of intravenous low-dose gemcitabine for patients with unresectable locally advanced or metastatic pancreatic cancer (LAPC or MPC) is evaluated. (2) Methods: A single-arm, single-center, institutional review board-approved prospective study was conducted between 2005 and 2015. Forty-five patients (23 LAPC, 22 MPC) were included. Patients received a weekly low dose of gemcitabine intravenously for three weeks followed by arterial administration of mitomycin C and epirubicin hydrochloride at tumor-supplying arteries on the fifth or sixth week. This treatment course was repeated at 1.5-to-2-month intervals. Overall survival (OS), local progression-free survival (LPFS), and therapeutic response were evaluated. LAPC or MPC were divided according to treatment compliance, excellent or poor (1 or 2), to subgroups L1, L2, M1, and M2. (3) Results: OS of LAPC and MPC were 23 months and 13 months, respectively. The OS of LAPC with excellent treatment compliance (subgroup L1, 10 patients) was 33 months with 31 months of LPFS, and four patients (40%) had a complete response (CR). The OS of the L1 subgroup was significantly longer than those of other subgroups L2, M1, and M2, which were 17 months, 17 months, and 8 months, respectively. As Grade 3 adverse effects, severe bone marrow suppression, interstitial pneumonitis, and hemolytic uremic syndrome were observed in six (13.0%), three (6.5%), and three (6.5%) patients, respectively. (4) Conclusions: Arterial DNA crosslinking with the systemic restraint of homologous recombination repair can be a new treatment option for LAPC.
A Scoping Review Examining Governance, Co-Creation, and Social and Ecological Justice in Living Labs Literature
Authors: Galway Lindsay P. , Levkoe Charles Z. , Portinga Rachel L. W. , Milun Kathryn
Published: January 2022

Living Labs (LLs) are increasingly being used as an approach to address complex sustainability-related challenges. Inspired by existing knowledge and practice gaps, calls for further examination of governance and co-creation in relation to LLs work, and our experiences in the Lake Superior Living Labs Network, we conducted a scoping review of the recent (2015–2019) LLs literature. This review focused on peer-reviewed LLs literature aimed at addressing sustainability-related challenges and involving universities as key collaborators specifically. This scoping review addressed the research questions: how are LLs conceptualized, described, and applied? how are LLs governed? How is co-creation supported in LLs work? and, are social and/or environmental justice considered in LLs work? From the 729 citations gathered in the electronic database searches, 48 papers were identified as relevant through the screening and eligibility assessment. We found that this literature is growing rapidly, highly interdisciplinary, and predominantly taking place within European urban centres. We summarize the findings in relation to our research questions and outline implications for interrogating governance, unpacking co-creation, and working towards social and ecological justice in LLs research and practice. We conclude by outlining four key research directions to advance LLs work, including, (1) expanding research across a greater diversity of settings; (2) examining and analyzing governance and power dynamics; (3) exploring how learning evolves via co-creation; and (4) examining how universities are impeding and/or supporting advances in relation to governance, co-creation, and justice in LLs work.
Study on Behavior of the Heat Exchanger with Conically-Corrugated Tubes and HDD Baffles
Authors: Wu Zhiwei , Qian Caifu
Published: January 2022

Baffles with holes in different diameters (or HDD baffles) and conically-corrugated tubes are respectively longitudinal flow baffle and high-efficiency heat exchange tubes proposed by the author. In this paper, vibrations of tube bundles with HDD baffles and fluid flow as well as heat transfer inside conically-corrugated tubes were numerically simulated, and the heat exchanger with conically-corrugated tubes and HDD baffles was tested for the heat transfer efficiency. It is found that compared with the traditional segmental baffles, tube bundle vibrations in heat exchangers, if using the HDD baffles, can be significantly reduced. Regarding heat transfer efficiency, conically-corrugated tubes are much better than smooth tubes and even better than other high-efficiency heat transfer tubes. Compared with the traditional heat exchangers, heat exchangers constructed with conically-corrugated tubes and the HDD baffles can provide better heat transfer efficiency and less tube bundle vibration.
Psychometric Properties of Scared-C Scale in a Romanian Community Sample and Its Future Utility for Dental Practice
Authors: Bucur Sorana-Maria , Moraru Adela , Adamovits Beata , Bud Eugen Silviu , Olteanu Cristian Doru , Vaida Luminița Ligia
Published: January 2022

The psychological management of children and adolescents in need of pedodontics or orthodontic treatments continues to be an essential objective in dental activity because along with the accuracy of the techniques that are used, anxiety reduction, and knowledge of how to approach the patient are necessary for the treatment to be successful. Therefore, our study aimed to validate the Screen for Child Anxiety Related Emotional Disorders questionnaire, the child version of 41 items (SCARED-C) in the Romanian population for later use in pediatric dentistry. The instrument showed moderate to good internal consistency (α Cronbach from 0.63 to 0.91 for the total scale) and good test–retest reliability (0.70) on a subset of a sample comprising 85 children. A confirmatory factorial analysis (CFA) was conducted to test the factor structure of the Romanian version of the SCARED-C; the results showed that SCARED-C has good psychometric properties that can be used for screening anxiety in Romanian children and adolescents. The implications of using the SCARED-C in dental practice are discussed. Future studies need to be conducted to explore the convergent and discriminative validity of the instrument and its sensitivity to current DSM-V criteria. Application on a pediatric dental sample is also required.
Comparison of Distance and Angular Analysis for Measurement of Hamstring Flexibility in Preschoolers
Authors: Hua Anke , Bai Jingyuan , Fan Yong , Wang Jian
Published: January 2022

The study aimed to (1) investigate the reliability and usefulness of a proposed angular analysis during a modified sit-and-reach (MSR) test, and (2) compare the proposed MSR angular analysis and the commonly used MSR distance to verify the influence of the anthropometric characteristics in preschoolers. 194 preschoolers participated in the study. Before testing, the anthropometric characteristics were collected. Each participant performed the MSR test twice. The MSR distance score was obtained from the starting point to the reaching point, while the MSR angle score was calculated according to the approximate hip flexion angle. Both the relative and absolute reliability were good for the angular analysis during an MSR test in preschoolers (ICC ranging from 0.82 to 0.91, CV% ranging from 8.21 to 9.40). The angular analysis demonstrated good usefulness, with a lower typical error than the smallest worthwhile change in 3- and 5-year-old groups. The MSR angle scores could eliminate the concern of the influence of anthropometric characteristics, while MSR distance and anthropometric characteristics (i.e., sitting height and arm length) were found to be weakly correlated. In conclusion, the angular analysis when performing the MSR test is reliable and appears to eliminate the concern regarding the limb length bias.
Staphylococcus lugdunensis Bacteremia with an Infected Aortic Thrombus in a Preterm Infant
Authors: Mani Srinivasan , Chandrasekharan Praveen
Published: January 2022

Staphylococcus lugdunensis is a rare cause of late-onset sepsis in preterm infants. To our best knowledge, we report the fourth case of a male preterm infant who developed fulminant late-onset sepsis due to Staphylococcus lugdunensis with persistent bacteremia secondary to an infected aortic thrombus confirmed with two positive blood cultures. Our patient was an extremely low birth weight growth-restricted infant born at 27 weeks gestation and initially required an umbilical arterial catheter for blood pressure and blood gas monitoring. The course of this neonate was complicated by severe respiratory distress syndrome that evolved into chronic lung disease along with multiple episodes of tracheitis. Hemodynamically, the infant had a significant patent ductus arteriosus, and an episode of medical necrotizing enterocolitis followed by Staphylococcus lugdunensis septicemia. He was diagnosed with an infected aortic thrombus, probably the occult focus responsible for the persistent bacteremia. After a 6-week course of intravenous antibiotics and 4-week course of anticoagulant therapy, the infant responded and recovered without complications.
Reference Values of Thromboelastometry Parameters in Healthy Term Neonates Using NATEM in Cord Blood Samples
Authors: Sulaj Alma , Tsaousi Marina , Karapati Eleni , Pouliakis Abraham , Iliodromiti Zoi , Boutsikou Theodora , Valsami Serena , Iacovidou Nicoletta , Politou Marianna , Sokou Rozeta
Published: January 2022

Background: ROTEM assay has gained increasing acceptance as a method for rapid and specific coagulation pathway assessment. However, its use in the neonatal population remains limited since reference ranges have not yet been established. Aims: (1) to determine reference ranges for healthy term neonates of ROTEM parameters using non-activated assay (NATEM) in cord blood samples; (2) to assess whether delivery mode, gender, gestational age, birth weight and blood group (ABO and Rhesus) of the neonate, coagulation disorder and anticoagulant medication of the mother have an impact on NATEM parameters. Methods: NATEM assay was conducted in cord blood samples of 189 term neonates without any medical history. Results: Reference ranges (2.5th and 97.5th percentiles) are established for clotting time (CT), clot formation time (CFT), α-angle, clot amplitude at 5, 10 and 20 min (A5, A10, A20), maximum clot firmness (MCF), lysis index at 30 and 60 min (LI30, LI60, %) and maximum clot elasticity (MCE). Reference ranges for NATEM are CT 182–499 s, CFT 63–176 s, α-angle 58–78°, A5 28–52 mm, A10 37–61 mm, A20 42–66 mm, MCF 43–67 mm, LI30 97–100%, LI60 87–98% and MCE 75–203. Male neonates appear to be more hypocoagulable than females. Conclusions: We demonstrate reference ranges for healthy term neonates in NATEM assay that could be used as a reference group for future studies of neonates with an underlying pathology.
Associations between Cultural Identity, Household Membership and Diet Quality among Native Hawaiian, Pacific Islander, and Filipino Infants in Hawaiʻi
Authors: Kai Jessie , Chen John J. , Braun Kathryn L. , Kaholokula Joseph Keaweʻaimoku , Novotny Rachel , Boushey Carol J. , Fialkowski Marie K.
Published: January 2022

Public health efforts to reduce diet-related health disparities experienced by indigenous peoples could be enhanced by efforts to improve complementary infant feeding practices. The latter is possible through interventions informed by cultural determinants. This cross-sectional secondary analysis explored possible determinants of the complementary feeding practices of Native Hawaiian, Pacific Islander, and/or Filipino infants (NHPIF) in Hawaiʻi, ages 3–12 months. The objective was to determine the association between caregiver cultural identity and infant household membership with indicators of infant diet healthfulness. The cultural identities, infant household memberships, early infant feeding practices and additional demographic information (infant age and sex, household income) were assessed via an online questionnaire. Surrogate reporting of the infants’ diets over four days was evaluated using an image-based mobile food record (mFR). Data collected by the mFR were evaluated to derive the World Health Organization’s minimum dietary diversity (MDD) indicator and food group consumption. Data were summarized by descriptive statistics and analyzed using multivariate linear and logistic regressions. Seventy infant participants, ages 3–12 months, and their primary caregivers completed the study. Of these, there were 56 infant participants between the age of 6–12 months. Approximately 10% of infants, ages 6–12 months, met MDD for all four days. Meeting MDD and the number of food groups consumed were significantly associated with age. Caregiver cultural identity, infant household membership and infant sex had non-significant associations with indicators of infant diet quality. Findings inform the influences shaping dietary patterns of Native Hawaiian, Pacific Islander and Filipino infants in Hawaiʻi.