bluuebunny/crossref_metadata_2025 huggingface dataset:
Nephronectin as a Matrix Effector in Cancer
Authors: Magnussen Synnøve Norvoll , Toraskar Jimita , Hadler-Olsen Elin , Steigedal Tonje S. , Svineng Gunbjørg
Published: February 2021

The extracellular matrix protein nephronectin plays an important regulatory role during embryonic development, controlling renal organogenesis through integrin α8β1 association. Nephronectin has three main domains: five N-terminal epidermal growth factor-like domains, a linker region harbouring two integrin-binding motifs (RGD and LFEIFEIER), and a C-terminal MAM domain. In this review, we look into the domain-related functions of nephronectin, and tissue distribution and expression. During the last two decades it has become evident that nephronectin also plays a role during cancer progression and in particular metastasis. Nephronectin is overexpressed in both human and mouse breast cancer compared to normal breast tissue where the protein is absent. Cancer cells expressing elevated levels of nephronectin acquire increased ability to colonise distant organs. In particular, the enhancer-motif (LFEIFEIER) which is specific to the integrin α8β1 association induces viability via p38 MAPK and plays a role in colonization. Integrins have long been desired as therapeutic targets, where low efficiency and receptor redundancy have been major issues. Based on the summarised publications, the enhancer-motif of nephronectin could present a novel therapeutic target.
Redox Imbalance and Biochemical Changes in Cancer by Probing Redox-Sensitive Mitochondrial Cytochromes in Label-Free Visible Resonance Raman Imaging
Authors: Abramczyk Halina , Brozek-Pluska Beata , Kopec Monika , Surmacki Jakub , Błaszczyk Maciej , Radek Maciej
Published: February 2021

To monitor redox state changes and biological mechanisms occurring in mitochondrial cytochromes in cancers improving methods are required. We used Raman spectroscopy and Raman imaging to monitor changes in the redox state of the mitochondrial cytochromes in ex vivo human brain and breast tissues at 532 nm, 633 nm, 785 nm. We identified the oncogenic processes that characterize human infiltrating ductal carcinoma (IDC) and human brain tumors: gliomas; astrocytoma and medulloblastoma based on the quantification of cytochrome redox status by exploiting the resonance-enhancement effect of Raman scattering. We visualized localization of cytochromes by Raman imaging in the breast and brain tissues and analyzed cytochrome c vibrations at 750, 1126, 1337 and 1584 cm−1 as a function of malignancy grade. We found that the concentration of reduced cytochrome c becomes abnormally high in human brain tumors and breast cancers and correlates with the grade of cancer. We showed that Raman imaging provides additional insight into the biology of astrocytomas and breast ductal invasive cancer, which can be used for noninvasive grading, differential diagnosis.
Analyzing Longitudinal wb-MRI Data and Clinical Course in a Cohort of Former Smoldering Multiple Myeloma Patients: Connections between MRI Findings and Clinical Progression Patterns
Authors: Wennmann Markus , Hielscher Thomas , Kintzelé Laurent , Menze Bjoern H. , Langs Georg , Merz Maximilian , Sauer Sandra , Kauczor Hans-Ulrich , Schlemmer Heinz-Peter , Delorme Stefan , Goldschmidt Hartmut , Weinhold Niels , Hillengass Jens , Weber Marc-André
Published: February 2021

The purpose of this study was to analyze size and growth dynamics of focal lesions (FL) as well as to quantify diffuse infiltration (DI) in untreated smoldering multiple myeloma (SMM) patients and correlate those MRI features with timepoint and cause of progression. We investigated 199 whole-body magnetic resonance imaging (wb-MRI) scans originating from longitudinal imaging of 60 SMM patients and 39 computed tomography (CT) scans for corresponding osteolytic lesions (OL) in 17 patients. All FLs >5 mm were manually segmented to quantify volume and growth dynamics, and DI was scored, rating four compartments separately in T1- and fat-saturated T2-weighted images. The majority of patients with at least two FLs showed substantial spatial heterogeneity in growth dynamics. The volume of the largest FL (p = 0.001, c-index 0.72), the speed of growth of the fastest growing FL (p = 0.003, c-index 0.75), the DI score (DIS, p = 0.014, c-index 0.67), and its dynamic over time (DIS dynamic, p < 0.001, c-index 0.67) all significantly correlated with the time to progression. Size and growth dynamics of FLs correlated significantly with presence/appearance of OL in CT within 2 years after the respective MRI assessment (p = 0.016 and p = 0.022). DIS correlated with decrease of hemoglobin (p < 0.001). In conclusion, size and growth dynamics of FLs correlate with prognosis and local bone destruction. Connections between MRI findings and progression patterns (fast growing FL—OL; DIS—hemoglobin decrease) might enable more precise diagnostic and therapeutic approaches for SMM patients in the future.
miR-449a Repression Leads to Enhanced NOTCH Signaling in TMPRSS2:ERG Fusion Positive Prostate Cancer Cells
Authors: Bauer Simone , Ratz Leonie , Heckmann-Nötzel Doreen , Kaczorowski Adam , Hohenfellner Markus , Kristiansen Glen , Duensing Stefan , Altevogt Peter , Klauck Sabine M. , Sültmann Holger
Published: February 2021

About 50% of prostate cancer (PCa) tumors are TMPRSS2:ERG (T2E) fusion-positive (T2E+), but the role of T2E in PCa progression is not fully understood. We were interested in investigating epigenomic alterations associated with T2E+ PCa. Using different sequencing cohorts, we found several transcripts of the miR-449 cluster to be repressed in T2E+ PCa. This repression correlated strongly with enhanced expression of NOTCH and several of its target genes in TCGA and ICGC PCa RNA-seq data. We corroborated these findings using a cellular model with inducible T2E expression. Overexpression of miR-449a in vitro led to silencing of genes associated with NOTCH signaling (NOTCH1, HES1) and HDAC1. Interestingly, HDAC1 overexpression led to the repression of HES6, a negative regulator of the transcription factor HES1, the primary effector of NOTCH signaling, and promoted cell proliferation by repressing the cell cycle inhibitor p21. Inhibition of NOTCH as well as knockdown of HES1 reduced the oncogenic properties of PCa cell lines. Using tissue microarray analysis encompassing 533 human PCa cores, ERG-positive areas exhibited significantly increased HES1 expression. Taken together, our data suggest that an epigenomic regulatory network enhances NOTCH signaling and thereby contributes to the oncogenic properties of T2E+ PCa.
Tumour-Infiltrating Lymphocytes (TILs) and PD-L1 Expression Correlate with Lymph Node Metastasis, High-Grade Transformation and Shorter Metastasis-Free Survival in Patients with Acinic Cell Carcinoma (AciCC) of the Salivary Glands
Authors: Hiss Selina , Eckstein Markus , Segschneider Patricia , Mantsopoulos Konstantinos , Iro Heinrich , Hartmann Arndt , Agaimy Abbas , Haller Florian , Mueller Sarina K.
Published: February 2021

Objectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Acinic Cell Carcinoma (AciCC) of the salivary glands, to enable a correlation with clinico-pathological features and to analyse their prognostic impact. Methods: This single centre retrospective study represents a cohort of 36 primary AciCCs with long-term clinical follow-up. Immunohistochemically defined immune cell subtypes, i.e., those expressing T-cell markers (CD3, CD4 and CD8) or a B-cell marker (CD20) were characterized on tumour tissue sections. The number of TILs was quantitatively evaluated using software for digital bioimage analysis (QuPath). PD-L1 expression on the tumour cells and on immune cells was assessed immunohistochemically employing established scoring criteria: tumour proportion score (TPS), Ventana immune cell score (IC-Score) and combined positive score (CPS). Results: Higher numbers of tumour-infiltrating T- and B-lymphocytes were significantly associated with high-grade transformation. Furthermore, higher counts of T-lymphocytes correlated with node-positive disease. There was a significant correlation between higher levels of PD-L1 expression and lymph node metastases as well as the occurrence of high-grade transformation. Moreover, PD-L1 CPS was associated with poor prognosis regarding metastasis-free survival (p = 0.049). Conclusions: The current study is the first to demonstrate an association between PD-L1 expression and lymph node metastases as well as grading in AciCCs. In conclusion, increased immune cell infiltration of T and B cells as well as higher levels of PD-L1 expression in AciCC in association with high-grade transformation, lymph node metastasis and unfavourable prognosis suggests a relevant interaction between tumour cells and immune cell infiltrates in a subset of AciCCs, and might represent a rationale for immune checkpoint inhibition.
Vaccine Increases the Diversity and Activation of Intratumoral T Cells in the Context of Combination Immunotherapy
Authors: Horn Lucas A. , Fousek Kristen , Hamilton Duane H. , Hodge James W. , Zebala John A. , Maeda Dean Y. , Schlom Jeffrey , Palena Claudia
Published: February 2021

Resistance to immune checkpoint blockade therapy has spurred the development of novel combinations of drugs tailored to specific cancer types, including non-inflamed tumors with low T-cell infiltration. Cancer vaccines can potentially be utilized as part of these combination immunotherapies to enhance antitumor efficacy through the expansion of tumor-reactive T cells. Utilizing murine models of colon and mammary carcinoma, here we investigated the effect of adding a recombinant adenovirus-based vaccine targeting tumor-associated antigens with an IL-15 super agonist adjuvant to a multimodal regimen consisting of a bifunctional anti-PD-L1/TGF-βRII agent along with a CXCR1/2 inhibitor. We demonstrate that the addition of vaccine induced a greater tumor infiltration with T cells highly positive for markers of proliferation and cytotoxicity. In addition to this enhancement of cytotoxic T cells, combination therapy showed a restructured tumor microenvironment with reduced Tregs and CD11b+Ly6G+ myeloid cells. Tumor-infiltrating immune cells exhibited an upregulation of gene signatures characteristic of a Th1 response and presented with a more diverse T-cell receptor (TCR) repertoire. These results provide the rationale for the addition of vaccine-to-immune checkpoint blockade-based therapies being tested in the clinic.
Anti-Tumor Effects of a Penetratin Peptide Targeting Transcription of E2F-1, 2 and 3a Is Enhanced When Used in Combination with Pemetrexed or Cisplatin
Authors: Rather Gulam Mohmad , Anyanwu Michael , Minko Tamara , Garbuzenko Olga , Szekely Zoltan , Bertino Joseph R.
Published: February 2021

Background: We tested the antitumor effects of a modified E2F peptide substituting D-Arg for L-Arg, conjugated to penetratin (PEP) against solid tumor cell lines and the CCRF-leukemia cell line, alone and in combination with pemetrexed or with cisplatin. For in-vivo studies, the peptide was encapsulated in PEGylated liposomes (PL-PEP) to increase half-life and stability. Methods: Prostate cancer (DU145 and PC3), breast cancer (MCF7, MDA-MB-468, and 4T1), lymphoma (CCRF-CEM), and non-small cell lung cancer (NSCLC) cell lines (H2009, H441, H1975, and H2228) were treated with D-Arg PEP in combination with cisplatin or pemetrexed. Western blot analysis was performed on the NSCLC for E2F-1, pRb, thymidylate synthase, and thymidine kinase. The H2009 cell line was selected for an in-vivo study. Results: When the PEP was combined with cisplatin and tested against solid tumor cell lines and the CCRF-CEM leukemia cell line, there was a modest synergistic effect. A marked synergistic effect was seen when the combination of pemetrexed and the PEP was tested against the adenocarcinoma lung cancer cell lines. The addition of the PEP to pemetrexed enhanced the antitumor effects of pemetrexed in a xenograft of the H2009 in mice. Conclusions: The D-Arg PEP in combination with cisplatin caused synergistic cell kill against prostate, breast, lung cancers, and the CCRF-CEM cell line. Marked synergy resulted when the D-Arg PEP was used in combination with pemetrexed against the lung adenocarcinoma cell lines. A xenograft study using the PL-PEP in combination with pemetrexed showed enhanced anti-tumor effects compared to each drug alone.
Identification of BXDC2 as a Key Downstream Effector of the Androgen Receptor in Modulating Cisplatin Sensitivity in Bladder Cancer
Authors: Jiang Guiyang , Teramoto Yuki , Goto Takuro , Mizushima Taichi , Inoue Satoshi , Ide Hiroki , Nagata Yujiro , Kashiwagi Eiji , Baras Alexander S. , Netto George J. , Yang Zhiming , Miyamoto Hiroshi
Published: February 2021

Underlying mechanisms for resistance to cisplatin-based chemotherapy in bladder cancer patients are largely unknown, although androgen receptor (AR) activity, as well as extracellular signal-regulated kinase (ERK) signaling, has been indicated to correlate with chemosensitivity. We also previously showed ERK activation by androgen treatment in AR-positive bladder cancer cells. Because our DNA microarray analysis in control vs. AR-knockdown bladder cancer lines identified BXDC2 as a potential downstream target of AR, we herein assessed its functional role in cisplatin sensitivity, using bladder cancer lines and surgical specimens. BXDC2 protein expression was considerably downregulated in AR-positive or cisplatin-resistant cells. BXDC2-knockdown sublines were significantly more resistant to cisplatin, compared with respective controls. Without cisplatin treatment, BXDC2-knockdown resulted in significant increases/decreases in cell proliferation/apoptosis, respectively. An ERK activator was also found to reduce BXDC2 expression. Immunohistochemistry showed downregulation of BXDC2 expression in tumor (vs. non-neoplastic urothelium), higher grade/stage tumor (vs. lower grade/stage), and AR-positive tumor (vs. AR-negative). Patients with BXDC2-positive/AR-negative muscle-invasive bladder cancer had a significantly lower risk of disease-specific mortality, compared to those with a BXDC2-negative/AR-positive tumor. Additionally, in those undergoing cisplatin-based chemotherapy, BXDC2 positivity alone (p = 0.083) or together with AR negativity (p = 0.047) was associated with favorable response. We identified BXDC2 as a key molecule in enhancing cisplatin sensitivity. AR-ERK activation may thus be associated with chemoresistance via downregulating BXDC2 expression in bladder cancer.
Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol
Authors: Dávila Fajardo Raquel , Furtwängler Rhoikos , van Grotel Martine , van Tinteren Harm , Pasqualini Claudia , Pritchard-Jones Kathy , Al-Saadi Reem , de Camargo Beatriz , Ramírez Villar Gema L. , Graf Norbert , Muracciole Xavier , Melchior Patrick , Saunders Daniel , Rübe Christian , van den Heuvel-Eibrink Marry M. , Janssens Geert O. , Verschuur Arnauld C.
Published: February 2021

Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol.
Systematic Identification of MACC1-Driven Metabolic Networks in Colorectal Cancer
Authors: Lisec Jan , Kobelt Dennis , Walther Wolfgang , Mokrizkij Margarita , Grötzinger Carsten , Jaeger Carsten , Baum Katharina , Simon Mareike , Wolf Jana , Beindorff Nicola , Brenner Winfried , Stein Ulrike
Published: February 2021

MACC1 is a prognostic and predictive metastasis biomarker for more than 20 solid cancer entities. However, its role in cancer metabolism is not sufficiently explored. Here, we report on how MACC1 impacts the use of glucose, glutamine, lactate, pyruvate and fatty acids and show the comprehensive analysis of MACC1-driven metabolic networks. We analyzed concentration-dependent changes in nutrient use, nutrient depletion, metabolic tracing employing 13C-labeled substrates, and in vivo studies. We found that MACC1 permits numerous effects on cancer metabolism. Most of those effects increased nutrient uptake. Furthermore, MACC1 alters metabolic pathways by affecting metabolite production or turnover from metabolic substrates. MACC1 supports use of glucose, glutamine and pyruvate via their increased depletion or altered distribution within metabolic pathways. In summary, we demonstrate that MACC1 is an important regulator of metabolism in cancer cells.
Rabdosianone I, a Bitter Diterpene from an Oriental Herb, Suppresses Thymidylate Synthase Expression by Directly Binding to ANT2 and PHB2
Authors: Watanabe Motoki , Yamada Yasumasa , Kurumida Yoichi , Kameda Tomoshi , Sukeno Mamiko , Iizuka-Ohashi Mahiro , Sowa Yoshihiro , Iizumi Yosuke , Takakura Hideki , Miyamoto Shingo , Sakai Toshiyuki , Mutoh Michihiro
Published: February 2021

Natural products have numerous bioactivities and are expected to be a resource for potent drugs. However, their direct targets in cells often remain unclear. We found that rabdosianone I, which is a bitter diterpene from an oriental herb for longevity, Isodon japonicus Hara, markedly inhibited the growth of human colorectal cancer cells by downregulating the expression of thymidylate synthase (TS). Next, using rabdosianone I-immobilized nano-magnetic beads, we identified two mitochondrial inner membrane proteins, adenine nucleotide translocase 2 (ANT2) and prohibitin 2 (PHB2), as direct targets of rabdosianone I. Consistent with the action of rabdosianone I, the depletion of ANT2 or PHB2 reduced TS expression in a different manner. The knockdown of ANT2 or PHB2 promoted proteasomal degradation of TS protein, whereas that of not ANT2 but PHB2 reduced TS mRNA levels. Thus, our study reveals the ANT2- and PHB2-mediated pleiotropic regulation of TS expression and demonstrates the possibility of rabdosianone I as a lead compound of TS suppressor.
Novel Immune Stimulant Amplifies Direct Tumoricidal Effect of Cancer Ablation Therapies and Their Systemic Antitumor Immune Efficacy
Authors: Korbelik Mladen , Hode Tomas , Lam Samuel S. K. , Chen Wei R.
Published: February 2021

Ablation therapies have emerged as an effective tool for destroying cancerous tissue, but for advanced and disseminated tumors their application remains mainly a palliative measure. However, it is becoming increasingly clear that this limitation can be redressed by the use of intratumoral immune stimulating agents for amplifying potential antitumor immune responses that are induced by ablation therapies. A novel immune stimulating drug IP-001, a specific variant of the N-dihydrogalactochitosan (GC) family of molecules, has shown to be effective against metastatic tumors, when combined with different forms tumor ablation. It acts as a multi-function immune stimulant both by directly inhibiting cell membrane repair and recycling of ablation-damaged tumor cells, and indirectly by sequestering ablation-released tumor antigens, as well as recruiting and stimulating antigen presenting cells to induce a potent Th1 type T cell response against the cancer. In this review, we briefly discuss the current applications of local ablation for cancer treatment and the effects of GC in combination with other ablation therapies, a therapeutic approach that is pioneering the field of Interventional Immuno-Oncology (IIO).
Transient Receptor Potential Canonical Channels in Health and Disease: A 2020 Update
Authors: Kirtley Priya R. , Sooch Gagandeep S. , White Fletcher A. , Obukhov Alexander G.
Published: February 2021

This 2020 Special Issue “TRPC channels” of Cells was dedicated to commemorating the 25th anniversary of discovery of the Transient Receptor Potential Canonical (TRPC) channel subfamily [...]
Differential Leukocyte and Platelet Profiles in Distinct Models of Traumatic Brain Injury
Authors: Hubbard William Brad , Banerjee Meenakshi , Vekaria Hemendra , Prakhya Kanakanagavalli Shravani , Joshi Smita , Wang Qing Jun , Saatman Kathryn E. , Whiteheart Sidney W. , Sullivan Patrick G.
Published: February 2021

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) model of contusion brain injury and the closed head injury (CHI) model of mild diffuse brain injury. Hematology parameters, platelet-neutrophil aggregation, and platelet respirometry were assessed acutely after injury. CCI resulted in an early drop in blood leukocyte counts, while CHI increased blood leukocyte counts early after injury. Platelet-neutrophil aggregation was altered acutely after CCI compared to sham. Furthermore, platelet bioenergetic coupling efficiency was transiently reduced at 6 h and increased at 24 h post-CCI. After CHI, oxidative phosphorylation in intact platelets was reduced at 6 h and increased at 24 h compared to sham. Taken together, these data demonstrate that brain trauma initiates alterations in platelet-leukocyte dynamics and platelet metabolism, which may be time- and injury-dependent, providing evidence that platelets carry a peripheral signature of brain injury. The unique trend of platelet bioenergetics after two distinct types of TBI suggests the potential for utilization in prognosis.
Mimickers of Urothelial Carcinoma and the Approach to Differential Diagnosis
Authors: Manini Claudia , Angulo Javier C. , López José I.
Published: February 2021

A broad spectrum of lesions, including hyperplastic, metaplastic, inflammatory, infectious, and reactive, may mimic cancer all along the urinary tract. This narrative collects most of them from a clinical and pathologic perspective, offering urologists and general pathologists their most salient definitory features. Together with classical, well-known, entities such as urothelial papillomas (conventional (UP) and inverted (IUP)), nephrogenic adenoma (NA), polypoid cystitis (PC), fibroepithelial polyp (FP), prostatic-type polyp (PP), verumontanum cyst (VC), xanthogranulomatous inflammation (XI), reactive changes secondary to BCG instillations (BCGitis), schistosomiasis (SC), keratinizing desquamative squamous metaplasia (KSM), post-radiation changes (PRC), vaginal-type metaplasia (VM), endocervicosis (EC)/endometriosis (EM) (müllerianosis), malakoplakia (MK), florid von Brunn nest proliferation (VB), cystitis/ureteritis cystica (CC), and glandularis (CG), among others, still other cellular proliferations with concerning histological features and poorly understood etiopathogenesis like IgG4-related disease (IGG4), PEComa (PEC), and pseudosarcomatous myofibroblastic proliferations (post-operative spindle cell nodule (POS), inflammatory myofibroblastic tumor (IMT)), are reviewed. Some of these diagnoses are problematic for urologists, other for pathologists, and still others for both. Interestingly, the right identification of their definitory features will allow their correct diagnoses, thus, avoiding overtreatment. The literature selected for this review also focuses on the immunohistochemical and/or molecular data useful to delineate prognosis.
Nanosecond-Pulse Laser Assisted Cold Spraying of Al–Cu Aluminum Alloy
Authors: Zhang Chen , Zhang Dongbin , Luo Can , Peng Weiping , Zang Xusheng
Published: February 2021

In this study, nanosecond-pulse laser is used in combination with cold spraying to form a hybrid solid-state forming technology: nanosecond-pulse laser assisted cold spraying. This method successfully manufactured Al-Cu high-strength aluminum alloy coatings. The nanosecond-pulse laser reduced the porosity of the coatings. The laser-induced micro-texture on the substrate surface had the ability of improving the bonding strength of the coating-substrate interface. The bonding strength was closely related to the depth of the micro-texture. The deeper micro-texture caused an unfused interface on the bottom of the texture, which produced voids and reduced the bonding strength. The nanosecond-pulse lasers can also increase the hardness of the coatings. The assistance of the nanosecond-pulse laser has proved to be an effective method to improve the quality of cold sprayed metal coatings.
Low-Damage and Self-Limiting (Al)GaN Etching Process through Atomic Layer Etching Using O2 and BCl3 Plasma
Authors: Hwang Il-Hwan , Cha Ho-Young , Seo Kwang-Seok
Published: February 2021

This paper reports on the use of low-damage atomic layer etching (ALE) performed using O2 and BCl3 plasma for etching (Al)GaN. The proposed ALE process led to excellent self-limiting etch characteristics with a low direct current (DC) self-bias, which resulted in a high linearity between the etching depth and number of cycles. The etching damage was evaluated using several methods, including atomic force microscopy, photoluminescence (PL), and X-ray photoelectron spectroscopy, and the I–V properties of the recessed Schottky diodes were compared with those of digital etching performed using O2 plasma and HCl solution. The electrical characteristics of the recessed Schottky diode fabricated using the proposed ALE process were superior to those of the diodes fabricated using the conventional digital etching process. Moreover, the ALE process yielded a higher PL intensity and N/(Al + Ga) ratio of the etched AlGaN surface, along with a smoother etched surface.
Preparation of Modified Silane Composite Emulsion and Its Effect on Surface Properties of Cement-Based Materials
Authors: Chen Xu , Geng Yongjuan , Li Shaochun , Hou Dongshuai , Meng Shuling , Gao Yan , Zhang Ping , Ai Hongxiang
Published: February 2021

A new type of waterproofing composite emulsion with high silane content and good economic efficiency was synthesized by sol synthesis. The effects of the amount and proportion of the compound emulsifier, amount of tetraethyl orthosilicate, and mixing time on the properties of the emulsifier were investigated. The optimum conditions for the synthesis of a tetraethyl orthosilicate/isobutyl triethoxysilane emulsion were determined. The composite emulsion was characterized by infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and energy-dispersive spectrometry, along with a series of microscopic testing techniques. It was verified that the composite emulsion was coated on the surface of the paste to form a hydrophobic protective layer. The results show that the composite emulsion can achieve a permeability and impervious effect after coating the concrete material, and microhardness tests prove that the composite emulsion will not reduce the surface hardness of cement-based materials.
Current Research in Pulsed Laser Deposition
Authors: Duta Liviu , Popescu Andrei C.
Published: February 2021

In industry, thin films proved invaluable for protection of tools withstanding high frictions and elevated temperatures, but also found successful applications as sensors, solar cells, bioactive coatings for implants, photocatalysis and in lithography [...]
Molecular Mechanism Study on Stereo-Selectivity of α or β Hydroxysteroid Dehydrogenases
Authors: Gao Miaomiao , Nie Kaili , Qin Meng , Xu Haijun , Wang Fang , Liu Luo
Published: February 2021

Hydroxysteroid dehydrogenases (HSDHs) are from two superfamilies of short-chain dehydrogenase (SDR) and aldo–keto reductase (AKR). The HSDHs were summarized and classified according to their structural and functional differences. A typical pair of enzymes, 7α–hydroxysteroid dehydrogenase (7α–HSDH) and 7β–hydroxysteroid dehydrogenase (7β–HSDH), have been reported before. Molecular docking of 7-keto–lithocholic acid(7–KLA) to the binary of 7β–HSDH and nicotinamide adenine dinucleotide phosphate (NADP+) was realized via YASARA, and a possible binding model of 7β–HSDH and 7–KLA was obtained. The α side of 7–KLA towards NADP+ in 7β–HSDH, while the β side of 7–KLA towards nicotinamide adenine dinucleotide (NAD+) in 7α–HSDH, made the orientations of C7–OH different in products. The interaction between Ser193 and pyrophosphate of NAD(P)+ [Ser193–OG⋯3.11Å⋯O1N–PN] caused the upturning of PN–phosphate group, which formed a barrier with the side chain of His95 to make 7–KLA only able to bind to 7β–HSDH with α side towards nicotinamide of NADP+. A possible interaction of Tyr253 and C24 of 7–KLA may contribute to the formation of substrate binding orientation in 7β–HSDH. The results of sequence alignment showed the conservation of His95, Ser193, and Tyr253 in 7β–HSDHs, exhibiting a significant difference to 7α–HSDHs. The molecular docking of other two enzymes, 17β–HSDH from the SDR superfamily and 3(17)α–HSDH from the AKR superfamily, has furtherly verified that the stereospecificity of HSDHs was related to the substrate binding orientation.
Effect of Biomass Fly Ash on Fresh and Hardened Properties of High Volume Fly Ash Mortars
Authors: Teixeira Elisabete , Camões Aires , Branco Fernando , Matos José
Published: February 2021

The objective of this work was to assess the use of biomass fly ash (BFA) as cement replacement material or as an alkalinity source in high volume fly ash mortar and concrete. Mortar formulations were prepared with different types of cement replacement: fly ash from thermal power plants, BFA, a blend of two pozzolans, and small amounts of BFA or/and hydrated lime (HL). Mortar formulations were tested both in the fresh and hardened state. The replacement of cement by the two fly ashes led to a decrease in the mechanical strength. The best strength values were obtained when higher HL content was introduced in mortars, however, mortars with the lower BFA content presented the best results for the majority of the tests. In general, BFA has a similar effect on cementitious mortars to coal fly ash, having good performance as cement replacement.
Topological Features of the Alluaudite-Type Framework and Its Derivatives: Synthesis and Crystal Structure of NaMnNi2(H2/3PO4)3
Authors: Aksenov Sergey M. , Yamnova Natalia A. , Kabanova Natalia A. , Volkov Anatoly S. , Gurbanova Olga A. , Deyneko Dina V. , Dimitrova Olga V. , Krivovichev Sergey V.
Published: February 2021

A new sodium manganese-nickel phosphate of alluaudite supergroup with the general formula NaMnNi2(H2/3PO4)3 was synthesized by a hydrothermal method. The synthesis was carried out in the temperature range from 540 to 660 K and at the general pressure of 80 atm from the oxides mixture in the molar ratio MnCl2: 2NiCl2: 2Na3PO4: H3BO3: 10H2O. The crystal structure was studied by a single-crystal X-ray diffraction analysis: space group C2/c (No. 15), a = 16.8913(4), b = 5.6406(1), c = 8.3591(3) Å, β = 93.919(3), V = 794.57(4) Å3. The compound belongs to the alluaudite structure type based upon a mixed hetero-polyhedral framework formed by MX6-octahedra and TX4-tetrahedra. The characteristic feature of the title compound is the absence of cations or H2O molecules in channel II, while the negative charge of the framework is balanced by the partial protonation of PO4 tetrahedra. The presence of the transition metals at the A-type sites results in the changes of stoichiometry and the local topological features. Topological analysis of the hetero-polyhedral alluaudite-type frameworks and its derivatives (johillerite-, KCd4(VO4)3-, and keyite-type) and quantitative characterization of their differences was performed by means of natural tilings.
Low-Temperature Co-Precipitation Synthesis of HoFeO3 Nanoparticles
Authors: Mai Vo Quang , Tien Nguyen Anh
Published: February 2021

In this research, we investigate and discuss the characteristics of HoFeO3 nanoparticles synthesized by the co-precipitation method at low temperature (t° ≤ 4 °C). The single-phase HoFeO3 samples with the orthorhombic structure formed after annealing of the precipitates at different temperatures up to 950 °C. The annealed HoFeO3 nanoparticles have an average crystal size of 10–20 nm (SEM, TEM). UV-Vis spectrum of HoFeO3 sample annealed at 750 °C showed strong UV and Vis absorption with small optical energy gap (Eg = 1.56 eV). In the range temperature of 100–300 K, the HoFeO3 samples showed superparamagnetic behaviour at 5 kOe with high magnetization (Ms = 1.3–2.4 emu/g) and very low susceptibility (χ << 1).
A Review of Canadian Cancer-Related Clinical Practice Guidelines and Resources during the COVID-19 Pandemic
Authors: Farah Eliya , Ali Rami , Tope Parker , El-Zein Mariam , Franco Eduardo , McGill Task Force on COVID-19 and Cancer
Published: February 2021

(1) Background: Preventive measures taken in response to the coronavirus disease 2019 (COVID-19) pandemic have adversely affected an entire range of cancer-related medical activities. The reallocation of medical resources, staff, and ambulatory services, as well as critical shortages in pharmaceutical and medical supplies have compelled healthcare professionals to prioritize patients with cancer to treatment and screening services based on a set of classification criteria in cancer-related guidelines. Cancer patients themselves have been affected on multiple levels, and addressing their concerns poses another challenge to the oncology community. (2) Methods: We conducted a Canada-wide search of cancer-related clinical practice guidelines on the management and prioritization of individuals into treatment and screening services. We also outlined the resources provided by Canadian cancer charities and patient advocacy groups to provide cancer patients, or potential cancer patients, with useful information and valuable support resources. (3) Results: The identified provincial guidelines emphasized cancer care (i.e., treatment) more than cancer control (i.e., screening). For cancer-related resources, a clear significance was placed on knowledge & awareness and supportive resources, mainly relating to mental health. (4) Conclusion: We provided a guidance document outlining cancer-related guidelines and resources that are available to healthcare providers and patients across Canada during the COVID-19 pandemic.
Improvement of EGFR Testing over the Last Decade and Impact of Delaying TKI Initiation
Authors: Blanc-Durand Félix , Florescu Marie , Tehfe Mustapha , Routy Bertrand , Alameddine Raafat , Tran-Thanh Danh , Blais Normand
Published: February 2021

Background: Epidermal growth factor receptor (EGFR) is the most common oncogenic mutation in lung adenocarcinoma and tyrosine kinase inhibitors (TKIs) have been considered standard treatment for more than a decade. However, time to initiation of TKIs (TTIT) from diagnosis is often delayed and represents a challenge for clinicians. We aimed to assess the impact of TTIT on clinical outcomes and complications. Method: TTIT was defined as the time between confirmed advanced diagnosis and the initiation of a TKI. Complications during this pre-TKI period were retrospectively collected from all patients with EGFR-mutant non small cell lung cancer (NSCLC) in our institution. Results: 102 patients were diagnosed with EGFR mutated NSCLC between 2006 and 2019. The median PFS and OS were 12.9 and 22.5 months, respectively. TTIT was 5.7 months (95% CI 3.4–8) with a significant decrease in the latter years of this cohort. During the pre-TKI period, 23 patients received chemotherapy as first line treatment, of which 5 developed severe adverse events and 3 were not fit to receive TKI thereafter. Additionally, 29 patients had rapid clinical deterioration before initiation of first line TKI and 16 had to be hospitalized. Among the patients presenting a performance status deterioration, their prognosis was markedly affected compared to the remainder of the cohort (p = 0.01). Conclusion: Our real-world evidence study supports the concept that a delay to treat EGFR mutant NSCLC with TKIs is associated with adverse events, patient progression, hospitalization, and decreased overall survival. Rapid molecular diagnosis, including access to ctDNA technology may circumvent these deleterious delays.
Implications of Historical and Contemporary Processes on Genetic Differentiation of a Declining Boreal Songbird: The Rusty Blackbird
Authors: Wilson Robert E. , Matsuoka Steven M. , Powell Luke L. , Johnson James A. , Demarest Dean W. , Stralberg Diana , Sonsthagen Sarah A.
Published: February 2021

The arrangement of habitat features via historical or contemporary events can strongly influence genomic and demographic connectivity, and in turn affect levels of genetic diversity and resilience of populations to environmental perturbation. The rusty blackbird (Euphagus carolinus) is a forested wetland habitat specialist whose population size has declined sharply (78%) over recent decades. The species breeds across the expansive North American boreal forest region, which contains a mosaic of habitat conditions resulting from active natural disturbance regimes and glacial history. We used landscape genomics to evaluate how past and present landscape features have shaped patterns of genetic diversity and connectivity across the species’ breeding range. Based on reduced-representation genomic and mitochondrial DNA, genetic structure followed four broad patterns influenced by both historical and contemporary forces: (1) an east–west partition consistent with vicariance during the last glacial maximum; (2) a potential secondary contact zone between eastern and western lineages at James Bay, Ontario; (3) insular differentiation of birds on Newfoundland; and (4) restricted regional gene flow among locales within western and eastern North America. The presence of genomic structure and therefore restricted dispersal among populations may limit the species’ capacity to respond to rapid environmental change.
Cetacean Strandings and Museum Collections: A Focus on Sicily Island Crossroads for Mediterranean Species
Authors: Lo Brutto Sabrina , Calascibetta Andrea , Pavan Gianni , Buffa Gaspare
Published: February 2021

The study examined the extent of the cetacean strandings in Italy, with a particular focus on Sicily Island. The paper aimed to contribute to the description of a pattern that contemplates the “regular and rare” cetacean species passage along the Sicilian coast. The estimate of marine cetacean strandings was extrapolated from the National Strandings Data Bank (BDS—Banca Dati Spiaggiamenti) and evaluated according to a subdivision in three coastal subregions: the Tyrrhenian sub-basin (northern Sicilian coast), the Ionian sub-basin (eastern Sicilian coast), and the Channel of Sicily (southern Sicilian coast). Along the Italian coast, more than 4880 stranding events have been counted in the period 1990–2019. Most of these were recorded in five Italian regions: Apulia, Sicily, Sardinia, Tuscany, and Calabria. Approximately 15% of the recorded strandings in Italy occurred on the Sicilian coast. In Sicily Island, 725 stranded cetaceans were recorded in 709 stranding events, resulting in approximately 20 carcasses every year; the total number of specimens identified to species level was 539. The distribution along the Sicilian coast was the following: 312 recorded in the Tyrrhenian sub-basin, 193 in the Ionian sub-basin, and 220 in the Channel of Sicily. Stenella coeruleoalba was the species that can be considered as the stable record along the time-lapse investigated, and some rare species have been recorded as well. The role of Sicily Island as a sentinel territory of the cetacean distribution for the central Mediterranean Sea and as a region receiving a marine resource suitable for the scientific research and cetological museum collections is discussed herein.
A Data Resource for Sulfuric Acid Reactivity of Organic Chemicals
Authors: Bains William , Petkowski Janusz Jurand , Seager Sara
Published: February 2021

We describe a dataset of the quantitative reactivity of organic chemicals with concentrated sulfuric acid. As well as being a key industrial chemical, sulfuric acid is of environmental and planetary importance. In the absence of measured reaction kinetics, the reaction rate of a chemical with sulfuric acid can be estimated from the reaction rate of structurally related chemicals. To allow an approximate prediction, we have collected 589 sets of kinetic data on the reaction of organic chemicals with sulfuric acid from 262 literature sources and used a functional group-based approach to build a model of how the functional groups would react in any sulfuric acid concentration from 60–100%, and between −20 °C and 100 °C. The data set provides the original reference data and kinetic measurements, parameters, intermediate computation steps, and a set of first-order rate constants for the functional groups across the range of conditions −20 °C–100 °C and 60–100% sulfuric acid. The dataset will be useful for a range of studies in chemistry and atmospheric sciences where the reaction rate of a chemical with sulfuric acid is needed but has not been measured.
FIKWaste: A Waste Generation Dataset from Three Restaurant Kitchens in Portugal
Authors: Pereira Lucas , Aguiar Vitor , Vasconcelos Fábio
Published: February 2021

In the era of big data and artificial intelligence, public datasets are becoming increasingly important for researchers to build and evaluate their models. This paper presents the FIKWaste dataset, which contains time series data for the volume of waste produced in three restaurant kitchens in Portugal. Organic (undifferentiated) and inorganic (glass, paper, and plastic) waste bins were monitored for a consecutive period of four weeks. In addition to the time series measurements, the FIKWaste dataset contains labels for waste disposal events, i.e., when the waste bins are emptied, and technical and non-technical details of the monitored kitchens.
Diagnostic and Management Difficulty of Bleeding Aorto-Duodenal Fistula Associated with Hodgkin’s Lymphoma
Authors: Nachmias Boaz , Bloom Allan I. , Gural Alexander
Published: February 2021

Primary aorto-enteric fistula (AEF) resulting from abdominal malignancy is a rare and often fatal complication. The few reports to date are mostly secondary to solid tumors. We present a case of a patient with refractory Hodgkin’s lymphoma who developed life-threatening AEF. We describe the diagnostic and therapeutic efforts, requiring a multi-disciplinary team of interventional radiology, gastroenterology, and transfusion medicine, resulting in a favorable outcome. Importantly, we offer several insights regarding the identification and management of high-risk patients, with an emphasis on pre-treatment considerations and urgent diagnosis and intervention.
Suitability of Bronchoscopic Biopsy Tissue Samples for Next-Generation Sequencing
Authors: Murakami Shuji , Yokose Tomoyuki , Nemoto Daiji , Suzuki Masaki , Usui Ryou , Nakahara Yoshiro , Kondo Tetsuro , Kato Terufumi , Saito Haruhiro
Published: February 2021

A sufficiently large tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥1 mm2) and tumor content rate (≥30%) on the success rate of the Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.
A Comprehensive Review of Computer-Aided Diagnosis of Major Mental and Neurological Disorders and Suicide: A Biostatistical Perspective on Data Mining
Authors: Mansourian Mahsa , Khademi Sadaf , Marateb Hamid Reza
Published: February 2021

The World Health Organization (WHO) suggests that mental disorders, neurological disorders, and suicide are growing causes of morbidity. Depressive disorders, schizophrenia, bipolar disorder, Alzheimer’s disease, and other dementias account for 1.84%, 0.60%, 0.33%, and 1.00% of total Disability Adjusted Life Years (DALYs). Furthermore, suicide, the 15th leading cause of death worldwide, could be linked to mental disorders. More than 68 computer-aided diagnosis (CAD) methods published in peer-reviewed journals from 2016 to 2021 were analyzed, among which 75% were published in the year 2018 or later. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was adopted to select the relevant studies. In addition to the gold standard, the sample size, neuroimaging techniques or biomarkers, validation frameworks, the classifiers, and the performance indices were analyzed. We further discussed how various performance indices are essential based on the biostatistical and data mining perspective. Moreover, critical information related to the Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines was analyzed. We discussed how balancing the dataset and not using external validation could hinder the generalization of the CAD methods. We provided the list of the critical issues to consider in such studies.