bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Investigation and Numerical Simulation of a Levy Hinged-Beam Cable Dome
Authors: Ding Mingmin , Luo Bin , Ding Shuyao , Shen Yuzhou , Huang Lifan
Published: March 2021

According to existing rigid roofing projects, a new structure called the Levy hinged-beam cable dome is proposed. By replacing the upper flexible cables with hinged beams, rigid plates can be installed overhead. To fulfill the requirements of integral tow-lifting construction, the setting criteria for the temporary hinged joints on ridge beams were presented. An 8-m diameter specimen was manufactured and monitored to investigate the structural configurations during the accumulative traction-hoisting construction process. Finally, the specimen was tested under full-span and half-span loading conditions, while a numerical model was built to verify the experimental values. The results show that in the early stages of traction-hoisting, the structure establishes the overall prestress and finds its internal force balance, while the entire structure is in a shape of “ω”. As the component’s internal force increases during the construction steps, and the local deformations of the hinged beams gradually decrease, with the entire structure changing from “ω” to “m”, and finally reach their designed states. Under full-span loads, large local deformations occurred at the HB-3 hinges, while the bending stresses of these hinged beams were relatively small. Under half-span loads, the loading part exhibits a downward appearance, while the unloading part exhibits upward deflection.
Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies
Authors: Chyuan I-Tsu , Chu Ching-Liang , Hsu Ping-Ning
Published: March 2021

Immune checkpoints play critical roles in the regulation of T-cell effector function, and the effectiveness of their inhibitors in cancer therapy has been established. Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy in general and cancer immunotherapy in particular. Immunotherapy has been indicated to reinvigorate antitumor T-cell activity and dynamically modulate anticancer immune responses. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. Overall, immunotherapy involves a certain degree of uncertainty and complexity. Research on the exploration of cellular and molecular factors within the tumor microenvironment (TME) aims to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies involving the specific targeting of the TME for cancer immunotherapy. The combination of this approach with other types of treatment, including immune checkpoint blockade therapy involving multiple agents, most of the responses and effects in cancer therapy could be significantly enhanced, but the appropriate combinations have yet to be established. Moreover, the in-depth exploration of complexity within the TME allows for the exploration of pathways of immune dysfunction. It may also aid in the identification of new therapeutic targets. This paper reviews recent advances in the improvement of therapeutic efficacy on the immune context of the TME and highlights its contribution to cancer immunotherapy.
Comparative Therapeutic Exploitability of Acute Adaptation Mechanisms to Photon and Proton Irradiation in 3D Head and Neck Squamous Cell Carcinoma Cell Cultures
Authors: Meerz Annina , Deville Sara Sofia , Müller Johannes , Cordes Nils
Published: March 2021

For better tumor control, high-precision proton beam radiation therapy is currently being intensively discussed relative to conventional photon therapy. Here, we assumed that radiation type-specific molecular response profiles in more physiological 3D, matrix-based head and neck squamous cell carcinoma (HNSCC) cell cultures can be identified and therapeutically exploited. While proton irradiation revealed superimposable clonogenic survival and residual DNA double strand breaks (DSB) relative to photon irradiation, kinome profiles showed quantitative differences between both irradiation types. Pharmacological inhibition of a subset of radiation-induced kinases, predominantly belonging to the mitogen-activated protein kinase (MAPK) family, failed to sensitize HNSCC cells to either proton or photon irradiation. Likewise, inhibitors for ATM, DNA-PK and PARP did not discriminate between proton and photon irradiation but generally elicited a radiosensitization. Conclusively, our results suggest marginal cell line-specific differences in the radiosensitivity and DSB repair without a superiority of one radiation type over the other in 3D grown HNSCC cell cultures. Importantly, radiation-induced activity changes of cytoplasmic kinases induced during the first, acute phase of the cellular radiation response could neither be exploited for sensitization of HNSCC cells to photon nor proton irradiation.
ECG Scoring for the Evaluation of Therapy-Naïve Cancer Patients to Predict Cardiotoxicity
Authors: Pohl Julia , Mincu Raluca-Ileana , Mrotzek Simone , Wakili Reza , Mahabadi Amir , Potthoff Sophia , Siveke Jens , Keller Ulrich , Landmesser Ulf , Rassaf Tienush , Anker Markus , Totzeck Matthias
Published: March 2021

Objective: To evaluate a new electrocardiographic (ECG) score reflecting domains of electrical and structural alterations in therapy-naïve cancer patients to assess their risk of cardiotoxicity. Methods: We performed a retrospective analysis of 134 therapy-naïve consecutive cancer patients in our two university hospitals concerning four ECG score parameters: Contiguous Q-waves, markers of left ventricular (LV) hypertrophy, QRS duration and JTc prolongation. Cardiotoxicity was assessed after a short-term follow-up (up to 12 months). Results: Of all the patients (n = 25), 19% reached 0 points, 50% (n = 67) reached 1 point, 25% (n = 33) reached 2 points, 5% (n = 7) reached 3 points and 0.7% reached 4 or 5 points (n = 1 respectively). The incidence of cardiotoxicity (n = 28 [21%]) increased with the ECG score, with 0 points at 0%, 1 point 7.5%, 2 points 55%, 3 points 71% and ≥3 points 50%. In the ROC (Receiver operating curves) analysis, the best cut-off for predicting cardiotoxicity was an ECG score of ≥2 points (sensitivity 82%, specificity 82%, AUC 0.84, 95% CI 0.77–0.92, p < 0.0001) which was then defined as a high-risk score. High-risk patients did not differ concerning their age, LV ejection fraction, classical cardiovascular risk factors or cardiac biomarkers compared to those with a low-risk ECG score. Conclusion: ECG scoring prior to the start of anti-cancer therapies may help to identify therapy-naïve cancer patients at a higher risk for the development of cardiotoxicity.
Neo-Fs Index: A Novel Immunohistochemical Biomarker Panel Predicts Survival and Response to Anti-Angiogenetic Agents in Clear Cell Renal Cell Carcinoma
Authors: Kim Jisup , Park Jee-Young , Shin Su-Jin , Lim Beom Jin , Go Heounjeong
Published: March 2021

Background: Frameshift indels have emerged as a predictor of immunotherapy response but were not evaluated yet to predict anti-angiogenetic agent (AAA) response or prognosis in clear cell renal cell carcinoma (ccRCC). Methods: Here, to develop biomarkers that predict survival and response to AAA, we evaluated the immunohistochemical expression of proteins whose genes frequently harbor frameshift indels in 638 ccRCC patients and correlated the individual and integrated markers with prognosis and AAA response. The mutational landscape was evaluated using targeted next-generation sequencing in 12 patients concerning protein markers. Immune gene signatures were retrieved from TCGA RNA seq data. Results: Five proteins (APC, NOTCH1, ARID1A, EYS, and filamin A) were independent adverse prognosticators and were incorporated into the Neo-fs index. Better overall, disease-specific and recurrence-free survival were observed with high Neo-fs index in univariate and multivariate survival analyses. Better AAA responses were observed with a high Neo-fs index, which reflected increased MHC class I, CD8+ T cell, cytolytic activity, and plasmacytoid dendritic cell signatures and decreased type II-IFN response signatures, as well as greater single-nucleotide variant (SNV) and indel counts. Conclusions: Neo-fs index, reflecting antitumor immune signature and more SNVs. and indels, is a powerful predictor of survival and AAA response in ccRCC.
Bioinformatic Analysis of the Nicotinamide Binding Site in Poly(ADP-Ribose) Polymerase Family Proteins
Authors: Manasaryan Garri , Suplatov Dmitry , Pushkarev Sergey , Drobot Viktor , Kuimov Alexander , Švedas Vytas , Nilov Dmitry
Published: March 2021

The PARP family consists of 17 members with diverse functions, including those related to cancer cells’ viability. Several PARP inhibitors are of great interest as innovative anticancer drugs, but they have low selectivity towards distinct PARP family members and exert serious adverse effects. We describe a family-wide study of the nicotinamide (NA) binding site, an important functional region in the PARP structure, using comparative bioinformatic analysis and molecular modeling. Mutations in the NA site and D-loop mobility around the NA site were identified as factors that can guide the design of selective PARP inhibitors. Our findings are of particular importance for the development of novel tankyrase (PARPs 5a and 5b) inhibitors for cancer therapy.
Current Status of Management and Outcome for Patients with Ewing Sarcoma
Authors: Hesla Asle Charles , Papakonstantinou Andri , Tsagkozis Panagiotis
Published: March 2021

Ewing sarcoma is the second most common bone sarcoma in children after osteosarcoma. It is a very aggressive malignancy for which systemic treatment has greatly improved outcome for patients with localized disease, who now see survival rates of over 70%. However, for the quarter of patients presenting with metastatic disease, survival is still dismal with less than 30% of patients surviving past 5 years. Patients with disease relapse, local or distant, face an even poorer prognosis with an event-free 5-year survival rate of only 10%. Unfortunately, Ewing sarcoma patients have not yet seen the benefit of recent years’ technical achievements such as next-generation sequencing, which have enabled researchers to study biological systems at a level never seen before. In spite of large multinational studies, treatment of Ewing sarcoma relies entirely on chemotherapeutic agents that have been largely unchanged for decades. As many promising modern therapies, including monoclonal antibodies, small molecules, and immunotherapy, have been disappointing to date, there is no clear candidate as to which drug should be investigated in the next large-scale clinical trial. However, the mechanisms driving tumor development in Ewing sarcoma are slowly unfolding. New entities of Ewing-like tumors, with fusion transcripts that are related to the oncogenic EWSR1-FLI1 fusion seen in the majority of Ewing tumors, are being mapped. These tumors, although sharing much of the same morphologic features as classic Ewing sarcoma, behave differently and may require a different treatment. There are also controversies regarding local treatment of Ewing sarcoma. The radiosensitive nature of the disease and the tendency for Ewing sarcoma to arise in the axial skeleton make local treatment very challenging. Surgical treatment and radiotherapy have their pros and cons, which may give rise to different treatment strategies in different centers around the world. This review article discusses some of these controversies and reproduces the highlights from recent publications with regard to diagnostics, systemic treatment, and surgical treatment of Ewing sarcoma.
Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias
Authors: Swatler Julian , Turos-Korgul Laura , Kozlowska Ewa , Piwocka Katarzyna
Published: March 2021

Both chronic myeloid leukemia and acute myeloid leukemia evade the immune response during their development and disease progression. As myeloid leukemia cells modify their bone marrow microenvironment, they lead to dysfunction of cytotoxic cells, such as CD8+ T cells or NK cells, simultaneously promoting development of immunosuppressive regulatory T cells and suppressive myeloid cells. This facilitates disease progression, spreading of leukemic blasts outside the bone marrow niche and therapy resistance. The following review focuses on main immunosuppressive features of myeloid leukemias. Firstly, factors derived directly from leukemic cells – inhibitory receptors, soluble factors and extracellular vesicles, are described. Further, we outline function, properties and origin of main immunosuppressive cells - regulatory T cells, myeloid derived suppressor cells and macrophages. Finally, we analyze interplay between recovery of effector immunity and therapeutic modalities, such as tyrosine kinase inhibitors and chemotherapy.
Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells
Authors: You Kyu Sic , Yi Yong Weon , Cho Jeonghee , Seong Yeon-Sun
Published: March 2021

There is an unmet medical need for the development of new targeted therapeutic strategies for triple-negative breast cancer (TNBC). With drug combination screenings, we found that the triple combination of the protein kinase inhibitors (PKIs) of the epidermal growth factor receptor (EGFR), v-akt murine thymoma viral oncogene homolog (AKT), and MAPK/ERK kinase (MEK) is effective in inducing apoptosis in TNBC cells. A set of PKIs were first screened in combination with gefitinib in the TNBC cell line, MDA-MB-231. The AKT inhibitor, AT7867, was identified and further analyzed in two mesenchymal stem-like (MSL) subtype TNBC cells, MDA-MB-231 and HS578T. A combination of gefitinib and AT7867 reduced the proliferation and long-term survival of MSL TNBC cells. However, gefitinib and AT7867 induced the activation of the rat sarcoma (RAS)/ v-raf-1 murine leukemia viral oncogene homolog (RAF)/MEK/ extracellular signal-regulated kinase (ERK) pathway. To inhibit this pathway, MEK/ERK inhibitors were further screened in MDA-MB-231 cells in the presence of gefitinib and AT7867. As a result, we identified that the MEK inhibitor, PD-0325901, further enhanced the anti-proliferative and anti-clonogenic effects of gefitinib and AT7867 by inducing apoptosis. Our results suggest that the dual inhibition of the AKT and MEK pathways is a novel potential therapeutic strategy for targeting EGFR in TNBC cells.
N-3 Long-Chain Polyunsaturated Fatty Acids, Eicosapentaenoic and Docosahexaenoic Acid, and the Role of Supplementation during Cancer Treatment: A Scoping Review of Current Clinical Evidence
Authors: Newell Marnie , Mazurak Vera , Postovit Lynne M. , Field Catherine J.
Published: March 2021

This scoping review examines the evidence for n-3 long-chain polyunsaturated fatty acid [LCPUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation in clinical cancer therapy. A comprehensive literature search was performed to identify relevant clinical intervention studies conducted through August 2020. Fifty-seven unique cancer trials, assessing EPA and/or DHA supplementation pre- or post-treatment, concomitant with neoadjuvant chemotherapy, radiation or surgery, or in palliative therapy were included. Breast, head and neck, gastrointestinal, gastric, colorectal/rectal, esophageal, leukemia/lymphoma, lung, multiple myeloma and pancreatic cancers were investigated. Across the spectrum of cancers, the evidence suggests that supplementation increased or maintained body weight, increased progression-free and overall survival, improved overall quality of life, resulted in beneficial change in immune parameters and decreased serious adverse events. Taken together, the data support that EPA and/or DHA could be used to improve outcomes important to the patient and disease process. However, before incorporation into treatment can occur, there is a need for randomized clinical trials to determine the dose and type of n-3 LCPUFA intervention required, and expansion of outcomes assessed and improved reporting of outcomes.
Exploring Older Women’s Attitudes to and Experience of Treatment for Advanced Ovarian Cancer: A Qualitative Phenomenological Study
Authors: Dumas Lucy , Lidington Emma , Appadu Laura , Jupp Philippa , Husson Olga , Banerjee Susana
Published: March 2021

Older women with ovarian cancer more often receive less intensive treatment and early discontinuation compared to younger women. There is little understanding of older women’s treatment experience and whether this contributes to declining intensive treatment. We aimed to explore the lived experience of older patients with advanced ovarian cancer undergoing chemotherapy, their treatment preferences and treatment burden. We conducted a phenomenological qualitative study with 15 women who had completed at least three cycles of first-line chemotherapy for advanced epithelial ovarian cancer, aged 65 years or older at the first cycle, at one tertiary cancer centre. We conducted interviews and focus groups and analysed the transcripts using inductive thematic analysis. Women reported a strong preference for active treatment despite treatment burden and toxicities. Participants undertook treatment to lengthen their lives for themselves and their families. Participants did not see age as a barrier to treatment. Patients expressed determination not to let cancer interfere with daily life. Women felt overwhelmed with information and struggled with daily tasks due to fatigue. Logistical issues, such as transportation and ineffective communication between healthcare providers, caused substantial distress. Despite these logistical burdens and toxicities, participants were positive about their care experience and desire for anticancer treatment. Older women may benefit from additional support to facilitate effective communication during the early stages of treatment.
Telomerase Regulation: A Role for Epigenetics
Authors: Dogan Fatma , Forsyth Nicholas R.
Published: March 2021

Telomerase was first described by Greider and Blackburn in 1984, a discovery ultimately recognized by the Nobel Prize committee in 2009. The three decades following on from its discovery have been accompanied by an increased understanding of the fundamental mechanisms of telomerase activity, and its role in telomere biology. Telomerase has a clearly defined role in telomere length maintenance and an established influence on DNA replication, differentiation, survival, development, apoptosis, tumorigenesis, and a further role in therapeutic resistance in human stem and cancer cells including those of breast and cervical origin. TERT encodes the catalytic subunit and rate-limiting factor for telomerase enzyme activity. The mechanisms of activation or silencing of TERT remain open to debate across somatic, cancer, and stem cells. Promoter mutations upstream of TERT may promote dysregulated telomerase activation in tumour cells but additional factors including epigenetic, transcriptional and posttranscriptional modifications also have a role to play. Previous systematic analysis indicated methylation and mutation of the TERT promoter in 53% and 31%, respectively, of TERT expressing cancer cell lines supporting the concept of a key role for epigenetic alteration associated with TERT dysregulation and cellular transformation. Epigenetic regulators including DNA methylation, histone modification, and non-coding RNAs are now emerging as drivers in the regulation of telomeres and telomerase activity. Epigenetic regulation may be responsible for reversible silencing of TERT in several biological processes including development and differentiation, and increased TERT expression in cancers. Understanding the epigenetic mechanisms behind telomerase regulation holds important prospects for cancer treatment, diagnosis and prognosis. This review will focus on the role of epigenetics in telomerase regulation.
The Ionic Organic Cage: An Effective and Recyclable Testbed for Catalytic CO2 Transformation
Authors: Wang Wenlong , Mao Yuanyou , Jin Jutao , Huo Yanping , Cui Lifeng
Published: March 2021

Porous organic cages (POC) are a class of relatively new molecular porous materials, whose concept was raised in 2009 by Cooper’s group and has rarely been directly used in the area of organic catalysis. In this contribution, a novel ionic quasi-porous organic cage (denoted as Iq-POC), a quaternary phosphonium salt, was easily synthesized through dynamic covalent chemistry and a subsequent nucleophilic addition reaction. Iq-POC was applied as an effective nucleophilic catalyst for the cycloaddition reaction of CO2 and epoxides. Owing to the combined effect of the relatively large molecular weight (compared with PPh3+I−) and the strong polarity of Iq-POC, the molecular catalyst Iq-POC displayed favorable heterogeneous nature (i.e., insolubility) in this catalytic system. Therefore, the Iq-POC catalyst could be easily separated and recycled by simple centrifugation method, and the catalyst could be reused five times without obvious loss of activity. The molecular weight augmentation route in this study (from PPh3+I− to Iq-POC) provided us a “cage strategy” of designing separable and recyclable molecular catalysts.
Modification of Ag8SnS6 Photoanodes with Incorporation of Zn Ions for Photo-Driven Hydrogen Production
Authors: Yeh Lin-Ya , Cheng Kong-Wei
Published: March 2021

In this study, Zn ions were incorporated into Ag8SnS6 thin films on glass and indium–tin–oxide-coated glass substrates using chemical bath deposition. Detailed procedures for the growth of Ag–Zn–Sn–S semiconductor films and their optical, physical and photoelectrochemical performances were investigated. X-ray diffraction patterns of samples revealed that kesterite Ag2ZnSnS4 phase with a certain amount of Ag8SnS6 phase can be obtained using ethylenediaminetetraacetic acid disodium salt and trisodium citrate as the chelating agent couples. Images of field-emission scanning electron microscope showed that plate-like microstructures with some spherical aggregates were observed for the sample at low Zn content. It changed to irregular spherical grains with the [Zn]/[Sn] ratios being higher than 0.95 in samples. The energy band gaps of the samples were in the range of 1.57–2.61 eV, depending on the [Zn]/[Sn] molar ratio in sample. From the Hall measurements, the carrier concentrations and mobilities of samples were in the ranges of 6.57 × 1012–1.76 × 1014 cm−3 and 7.14–39.22 cm2/V·s, respectively. All samples were n-type semiconductors. The maximum photoelectrochemical performance of sample was 1.38 mA/cm2 in aqueous 0.25 M K2SO3 and 0.35 M Na2S solutions.
Nicotinamide Treatment Facilitates Mitochondrial Fission through Drp1 Activation Mediated by SIRT1-Induced Changes in Cellular Levels of cAMP and Ca2+
Authors: Song Seon Beom , Park Jin Sung , Jang So Young , Hwang Eun Seong
Published: March 2021

Mitochondrial autophagy (or mitophagy) is essential for mitochondrial quality control, which is critical for cellular and organismal health by attenuating reactive oxygen species generation and maintaining bioenergy homeostasis. Previously, we showed that mitophagy is activated in human cells through SIRT1 activation upon treatment of nicotinamide (NAM). Further, mitochondria are maintained as short fragments in the treated cells. In the current study, molecular pathways for NAM-induced mitochondrial fragmentation were sought. NAM treatment induced mitochondrial fission, at least in part by activating dynamin-1-like protein (Drp1), and this was through attenuation of the inhibitory phosphorylation at serine 637 (S637) of Drp1. This Drp1 hypo-phosphorylation was attributed to SIRT1-mediated activation of AMP-activated protein kinase (AMPK), which in turn induced a decrease in cellular levels of cyclic AMP (cAMP) and protein kinase A (PKA) activity, a kinase targeting S637 of Drp1. Furthermore, in NAM-treated cells, cytosolic Ca2+ was highly maintained; and, as a consequence, activity of calcineurin, a Drp1-dephosphorylating phosphatase, is expected to be elevated. These results suggest that NAD+-mediated SIRT1 activation facilitates mitochondrial fission through activation of Drp1 by suppressing its phosphorylation and accelerating its dephosphorylation. Additionally, it is suggested that there is a cycle of mitochondrial fragmentation and cytosolic Ca2+-mediated Drp1 dephosphorylation that may drive sustained mitochondrial fragmentation.
Muscle Enriched Lamin Interacting Protein (Mlip) Binds Chromatin and Is Required for Myoblast Differentiation
Authors: Ahmady Elmira , Blais Alexandre , Burgon Patrick G.
Published: March 2021

Muscle-enriched A-type lamin-interacting protein (Mlip) is a recently discovered Amniota gene that encodes proteins of unknown biological function. Here we report Mlip’s direct interaction with chromatin, and it may function as a transcriptional co-factor. Chromatin immunoprecipitations with microarray analysis demonstrated a propensity for Mlip to associate with genomic regions in close proximity to genes that control tissue-specific differentiation. Gel mobility shift assays confirmed that Mlip protein complexes with genomic DNA. Blocking Mlip expression in C2C12 myoblasts down-regulates myogenic regulatory factors (MyoD and MyoG) and subsequently significantly inhibits myogenic differentiation and the formation of myotubes. Collectively our data demonstrate that Mlip is required for C2C12 myoblast differentiation into myotubes. Mlip may exert this role as a transcriptional regulator of a myogenic program that is unique to amniotes.
Patient-Reported Outcomes of Bladder and Bowel Control in Children with Spina Bifida
Authors: Träff Helen , Börjesson Anna , Salö Martin
Published: March 2021

Background: The primary aim was to describe patient-reported morbidity from neurogenic bladder and bowel dysfunction in a cohort of children with spina bifida. The secondary aim was to describe the overall surgical burden in these children. Methods: Children with meningocele or myelomeningocele, born between 2000–2016, and followed by a tertiary spina bifida center were evaluated in a cross-sectional cohort study using data from charts and a prospective national follow-up program. Results: In the group of 62 patients, clean intermittent catheterization (CIC) was used by 47 (76%) of the patients, and anticholinergic treatment was used by 36 (58%). More than one third of the patients reported inadequate results with daily urinary leakage. Laxatives and enema were used regularly by 45 (73%) and 39 (63%) patients, respectively. Inadequate results were reported by seven (11%) patients. One or more urogenital or gastrointestinal operations had been performed in 26 (42%) patients, with a total of 109 procedures overall. Conclusions: Despite substantial bowel and bladder management, a significant portion of children suffered from inadequate results concerning bladder and bowel control. Many surgeries were performed in a defined group of the children. Prospective, long-term studies can evaluate if more aggressive medical and/or surgical management could increase bowel and bladder control.
Outcomes in Establishing Individual Vessel Patency for Pediatric Pulmonary Vein Stenosis
Authors: Callahan Ryan , Gauvreau Kimberlee , Marshall Audrey C. , Sena Laureen M. , Baird Christopher W. , Ireland Christina M. , McEnaney Kerry , Bjornlund Elsa C. , Mendonca Juliana T. , Jenkins Kathy J.
Published: March 2021

The purpose of this study was to determine what patient and pulmonary vein characteristics at the diagnosis of intraluminal pulmonary vein stenosis (PVS) are predictive of individual vein outcomes. A retrospective, single-center, cohort sub-analysis of individual pulmonary veins of patients enrolled in the clinical trial NCT00891527 using imatinib mesylate +/− bevacizumab as adjunct therapy for the treatment of multi-vessel pediatric PVS between March 2009 and December 2014 was performed. The 72-week outcomes of the individual veins are reported. Among the 48 enrolled patients, 46 patients and 182 pulmonary veins were included in the study. Multivariable analysis demonstrated that patients with veins without distal disease at baseline (odds ratio, OR 3.69, 95% confidence interval, CI [1.52, 8.94], p = 0.004), location other than left upper vein (OR 2.58, 95% CI [1.07, 6.19], p = 0.034), or veins in patients ≥ 1 y/o (OR 5.59, 95% CI [1.81, 17.3], p = 0.003) were at higher odds of having minimal disease at the end of the study. Veins in patients who received a higher percentage of eligible drug doses required fewer reinterventions (IRR 0.76, 95% CI [0.68, 0.85], p < 0.001). The success of a multi-modal treatment approach to aggressive PVS depends on the vein location, disease severity, and drug dose intensity.
In-Situ Repair Plasma-Induced Damage and Cap Dielectric Barrier for Porous Low-Dielectric-Constant Materials by HMDS Plasma Treatment
Authors: Lee Chih-Yen , Yan Chi-Yang , Cheng Yi-Lung
Published: March 2021

Plasma damage and metal ion penetration are critical issues for porous low-dielectric-constant (low-k) materials used in the back-end-of-line interconnects. This study proposed a novel process with in-situ repairing plasma-induced damage and capping a barrier for porous low-k materials by Hexamethyldisilazane (HDMS) plasma treatment. For a plasma-damaged porous low-k material, its surface hydrophilic state was transformed to hydrophobic state by HDMS plasma treatment, revealing that damage was repaired. Simultaneously, a dielectric film was capped onto the porous low-k material, and displayed better barrier capability against Cu migration. Additionally, the breakdown reliability of the stacked dielectric was enhanced by the means of HDMS plasma treatment. The optimized HDMS plasma treatment time was found to be 10 s. Therefore, this proposed HDMS plasma treatment processing is a promising technique for highly applicable low-k material used for advanced technology nodes.
RETRACTED: Efficacy of Mesenchymal Stem Cell and Vitamin D in the Treatment of Diabetes Mellitus Induced in a Rat Model: Pancreatic Tissues
Authors: Hamza Reham , Al-Eisa Rasha , El-Shenawy Nahla
Published: March 2021

Treatment with mesenchyme stem cells (MSCs) plays a significant role in the therapies of many diseases such as diabetics. Vitamin D plays a significant role in the development of insulin and can increase the insulin action sensitivity of peripheral tissues. Moreover, there is limited research concerning the mechanism of the therapeutic action of MSCs with the combination of vitamin D (vit. D). Therefore, we evaluated the effect of MSC intervention in a diabetic animal model. Diabetes was induced by streptozotocin (STZ) injection at a dose of 50 mg/kg in adult male rats The diabetic rats were injected with MSCs derived from bone marrow (2 × 106 per rat), either alone or in combination with vit. D through the tail vein for four weeks. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, and lipid profile levels were determined. Pancreatic oxidative stress, histology, and electron microscopy were evaluated, and the gene expression of cytokines was assessed by real-time polymerase chain reaction PCR. MSC treatment suppressed pancreatic inflammatory cytokine secretion and oxidative stress in diabetic rats, resulting in improved pancreatic histology and cellular structure, and the complication of hyperglycemia was observed. Engrafted MSCs were found inside degraded pancreatic regions and regulated inflammatory cytokines. Our results demonstrated that treatment with MSCs and vit. D in combination prevented pancreatic injury via antioxidant and immune regulation in diabetic rats, contributing to the prevention of pancreatic dysfunction, improvement of lipid metabolism, and regulation of cytokine gene expression compared with each one separately. All these mechanisms also improved the histological structure of the pancreas based on transmission electron microscopy. The combination of MSCs and vit. D appears to have contributed to a greater improvement in the diabetic pancreatic complication of rats than was observed by each one separately. Therefore, this association can be used as antidiabetic therapy.
Fast Tunable Biological Fluorescence Detection Device with Integrable Liquid Crystal Filter
Authors: Yang Qing , Sun Tong , Wu Xinyu , Cui Guangchao , Yang Mengzheng , Bai Zhongyang , Wang Lin , Li Helin , Chen Wenjing , Leng Qunwen , Puers Robert , Frederik Ceyssens , Kraft Michael , Song Qinglin , Fang Huabin , Tian Dewen , Wang Dexin , Zhao Huijie , Zhao Weisheng , Nie Tianxiao , Guo Qi , Wen Lianggong
Published: March 2021

Detecting a variety of biological samples accurately and swiftly in an integrated way is of great practical significance. Currently, biofluorescent spectrum detection still largely relies on microscopic spectrometers. In this study, we propose an integrable method to detect biofluorescent spectrums with designed liquid crystal tunable filter (LCTF), in order to identify typical biological samples such as cells and bacteria. Hela cells labeled with red and green fluorescent proteins and Pseudomonas with fluorescence wavelengths of 610 nm, 509 nm and 450 nm, respectively, are inspected. High-resolution (6 μm) biofluorescent results have been achieved, together with clear images of the Hela cell clusters and the Pseudomonas bacteria colonies. Biofluorescence signals can be detected at a high transmittance (above 80%), and the response time of the device can reach 20 ms or below. The proposed method has the potential to be integrated into a microfluidic system to detect and identify the biofluorescent signals as a high throughput, low-cost option, for both high resolution and large field observation applications.
Synchrotron Radiation-Based Refraction-Contrast Tomographic Images Using X-ray Dark-Field Imaging Optics in Human Lung Adenocarcinoma and Histologic Correlations
Authors: Yi Eunjue , Sunaguchi Naoki , Lee Jeong Hyeon , Kim Chul-Yong , Lee Sungho , Jheon Sanghoon , Ando Masami , Seok Yangki
Published: March 2021

The aim of this study was to evaluate the clinical implication of synchrotron radiation imaging techniques for human lung adenocarcinoma in comparison with pathologic examination. A refraction-based tomographic imaging technique called the X-ray dark-field imaging (XDFI) method was used to obtain computed tomographic images of human lung adenocarcinoma at the beam line at Photon Factory BL 14B at the High Energy Accelerator Research Organization (KEK) in Tsukuba, Japan. Images of normal lung tissue were also obtained using the same methods and reconstructed as 3D images. Both reconstructed images were compared with pathologic examinations from histologic slides which were made with identical samples. Pulmonary alveolar structure including terminal bronchioles, alveolar sacs, and vasculatures could be identified in synchrotron radiation images of normal lung. Hyperplasia of interstitial tissue and dysplasia of alveolar structures were noticed in images of lung adenocarcinoma. Both synchrotron radiation images were considerably correlated with images from histologic slides. Lepidic patterns of cancer tissue were distinguished from the invasive area in synchrotron radiation images of lung adenocarcinoma. Refraction-contrast tomographic techniques using synchrotron radiation could provide high-resolution images of lung adenocarcinoma which are compatible with those from pathologic examinations.
Volumetric MRI Analysis of Brain Structures in Patients with History of First and Repeated Suicide Attempts: A Cross Sectional Study
Authors: Sarkinaite Milda , Gleizniene Rymante , Adomaitiene Virginija , Dambrauskiene Kristina , Raskauskiene Nijole , Steibliene Vesta
Published: March 2021

Structural brain changes are found in suicide attempters and in patients with mental disorders. It remains unclear whether the suicidal behaviors are related to atrophy of brain regions and how the morphology of specific brain areas is changing with each suicide attempt. The sample consisted of 56 patients hospitalized after first suicide attempt (first SA) (n = 29), more than one suicide attempt (SA > 1) (n = 27) and 54 healthy controls (HC). Brain volume was measured using FreeSurfer 6.0 automatic segmentation technique. In comparison to HC, patients with first SA had significantly lower cortical thickness of the superior and rostral middle frontal areas, the inferior, middle and superior temporal areas of the left hemisphere and superior frontal area of the right hemisphere. In comparison to HC, patients after SA > 1 had a significantly lower cortical thickness in ten areas of frontal cortex of the left hemisphere and seven areas of the right hemisphere. The comparison of hippocampus volume showed a significantly lower mean volume of left and right parts in patients with SA > 1, but not in patients with first SA. The atrophy of frontal, temporal cortex and hippocampus parts was significantly higher in repeated suicide attempters than in patients with first suicide attempt.
A Novel Tongue Pressure Measurement Instrument with Wireless Mobile Application Control Function and Disposable Positioning Mouthpiece
Authors: Liu Hsiu-Yueh , Chen Chun-Hung , Kuo Chao-Hung , Feng Ming-Chu , Chen Jen-Hao , Wang Hsuan-Wen , Chen Kun-Chun , Lin Chun-Li
Published: March 2021

This study developed a novel chair-side tongue pressure (TP) measuring instrument with a disposable positioning mouthpiece controlled using a smartphone application (APP), denoted as the TP wireless application (TPWA). The mouthpiece was designed with a palate-shaped air balloon containing a tongue contact bump and a plastic bite positioning tube. Fatigue load testing was performed to evaluate mouthpiece durability by applying 700 displacement cycles (50 times a day for one week during training, with twice the safety factor) on the air balloon. The main component used in developing this instrument was a silicon pressure sensor equipped with wireless Bluetooth connection. Young (52 adults; mean age = 20.23 ± 2.17) and elderly (40 adults; mean age = 72.60 ± 7.03) individuals participated in the test with the new instrument, with the results compared to those of a commercial device. The TPWA mouthpiece fatigue test showed that mean response pressures were maintained at 12 kPa. No significant (p > 0.05) differences were found during testing repetitions 0–10 and 701–710. There were no significant differences in the maximum TP values presented between the test sequences using different instruments for young and elderly participants. The TPWA results showed that TP values gradually decreased with increasing age (40.77 kPa for young and 16.55 kPa for elderly participants). The maximum TP for males (43.51 kPa) was significantly larger than that for females (35.14 kPa) in the young group, but an opposite trend was seen in the elderly group (12.97 for males and 17.59 for females). Thus, this study developed a novel chair-side TP measurement instrument with Bluetooth wireless mobile application control. A durable positioning oral mouthpiece was approved for measuring pressure sufficiently, reliably, and precisely for TP screening.
Measuring Spinal Mobility Using an Inertial Measurement Unit System: A Reliability Study in Axial Spondyloarthritis
Authors: O’Grady Megan , O’Dwyer Tom , Connolly James , Condell Joan , Esquivel Karla Muñoz , O’Shea Finbar D. , Gardiner Philip , Wilson Fiona
Published: March 2021

The objectives of this study were to evaluate the reliability of wearable inertial motion unit (IMU) sensors in measuring spinal range of motion under supervised and unsupervised conditions in both laboratory and ambulatory settings. A secondary aim of the study was to evaluate the reliability of composite IMU metrology scores (IMU-ASMI (Amb)). Forty people with axSpA participated in this clinical measurement study. Participant spinal mobility was assessed by conventional metrology (Bath Ankylosing Spondylitis Metrology Index, linear version—BASMILin) and by a wireless IMU sensor-based system which measured lumbar flexion-extension, lateral flexion and rotation. Each sensor-based movement test was converted to a normalized index and used to calculate IMU-ASMI (Amb) scores. Test-retest reliability was evaluated using intra-class correlation coefficients (ICC). There was good to excellent agreement for all spinal range of movements (ICC > 0.85) and IMU-ASMI (Amb) scores (ICC > 0.87) across all conditions. Correlations between IMU-ASMI (Amb) scores and conventional metrology were strong (Pearson correlation ≥ 0.85). An IMU sensor-based system is a reliable way of measuring spinal lumbar mobility in axSpA under supervised and unsupervised conditions. While not a replacement for established clinical measures, composite IMU-ASMI (Amb) scores may be reliably used as a proxy measure of spinal mobility.
A Novel Approach on Microwave Hyperthermia
Authors: Altintas Gulsah , Akduman Ibrahim , Janjic Aleksandar , Yilmaz Tuba
Published: March 2021

Microwave hyperthermia (MH) requires the selective focusing of microwave energy on the targeted region while minimally affecting the healthy tissue. Emerging from the simple nature of the linear antenna arrays, this work demonstrates focusing maps as an application guide for MH focusing by adjusting the antenna phase values. The focusing of the heating potential (HP) on different density breast models is performed via the proposed method using Vivaldi antennas. The effect of the tumor conductivity on the focusing is discussed. As a straightforward approach and utilizing the Vivaldi antennas, the system can be further combined with MH monitoring application.
Exploring Indigenous Science to Identify Contents and Contexts for Science Learning in Order to Promote Education for Sustainable Development
Authors: Zidny Robby , Solfarina S , Aisyah Ratna Sari Siti , Eilks Ingo
Published: March 2021

Indigenous science is comprised of the science-related knowledge and associated practices of indigenous cultures. Indigenous science provides rich contexts that can contribute to understanding the relationship of sociocultural life and environmental ethics in certain communities. It can also lead to better reflection upon Western modern views of science. Based on a qualitative analysis of indigenous science in the Baduy community (Indonesia), we describe how indigenous science can provide relevant contexts for students to learn scientific concepts, as well as help them to recognise the value of promoting sustainability. We present potential topics encompassing the sociocultural context of Baduy science that can be associated with sustainability issues. Topics were identified from six themes (agriculture, medicine, natural dyes, household chemicals, renewable energy, and astronomy). Potential implications of these topics to science learning are also presented. We view contextualization of science teaching and learning by indigenous science as a promising source to enhance students’ perception of the relevance of science learning. It can also promote education for sustainable development.
Investigation on a 220 GHz Quasi-Optical Antenna for Wireless Power Transmission
Authors: Han Meng , Guan Xiaotong , Einat Moshe , Fu Wenjie , Yan Yang
Published: March 2021

This paper investigates a 220 GHz quasi-optical antenna for millimeter-wave wireless power transmission. The quasi-optical antenna consists of an offset dual reflector, and fed by a Gaussian beam that is based on the output characteristics of a high-power millimeter-wave radiation source-gyrotron. The design parameter is carried on by a numerical code based on geometric optics and vector diffraction theory. To realize long-distance wireless energy transmission, the divergence angle of the output beam must be reduced. Electromagnetic simulation results show that the divergence angle of the output beam of the 5.6 mm Gaussian feed source has been significantly reduced by the designed quasi-optical antenna. The far-field divergence angle of the quasi-optical antenna in the E plane and H plane is 1.0596° and 1.0639°, respectively. The Gaussian scalar purity in the farthest observation field (x = 1000 m) is 99.86%. Thus, the quasi-optical antenna can transmit a Gaussian beam over long-distance and could be used for millimeter-wave wireless power transmission.
AlGaN Channel High Electron Mobility Transistors with Regrown Ohmic Contacts
Authors: Abid Idriss , Mehta Jash , Cordier Yvon , Derluyn Joff , Degroote Stefan , Miyake Hideto , Medjdoub Farid
Published: March 2021

High power electronics using wide bandgap materials are maturing rapidly, and significant market growth is expected in a near future. Ultra wide bandgap materials, which have an even larger bandgap than GaN (3.4 eV), represent an attractive choice of materials to further push the performance limits of power devices. In this work, we report on the fabrication of AlN/AlGaN/AlN high-electron mobility transistors (HEMTs) using 50% Al-content on the AlGaN channel, which has a much wider bandgap than the commonly used GaN channel. The structure was grown by metalorganic chemical vapor deposition (MOCVD) on AlN/sapphire templates. A buffer breakdown field as high as 5.5 MV/cm was reported for short contact distances. Furthermore, transistors have been successfully fabricated on this heterostructure, with low leakage current and low on-resistance. A remarkable three-terminal breakdown voltage above 4 kV with an off-state leakage current below 1 μA/mm was achieved. A regrown ohmic contact was used to reduce the source/drain ohmic contact resistance, yielding a drain current density of about 0.1 A/mm.
Impact of the Chaotic Synchronization’s Stability on the Performance of QCPSK Communication System
Authors: Babajans Ruslans , Cirjulina Darja , Grizans Juris , Aboltins Arturs , Pikulins Dmitrijs , Zeltins Maris , Litvinenko Anna
Published: March 2021

The current work presents a study of the implementation of a quadrature chaos phase-shift keying communication system (QCPSK) based on the employment of different chaos oscillators. The research takes two directions, with one being the study of the chaos synchronization’s noise immunity for several chaos oscillators that are the potential core blocks of the QCPSK system. The correlation coefficient over time is used to estimate the synchronization noise immunity. The second direction is the estimation of the QCPSK system’s baseband model performance in the AWGN propagation channel using the bit error ratio (BER) as the estimation method for several chaos oscillators employed as the core of the QCPSK system’s model.