bluuebunny/crossref_metadata_2025 huggingface dataset:
State of the Art on Heat Pumps for Residential Buildings
Authors: Wang Zheng , Luther Mark B. , Amirkhani Mehdi , Liu Chunlu , Horan Peter
Published: August 2021

Heat Pumps are becoming one of the most considered mechanical conditioning equipment in our buildings. While they are popular, there appears to be quite a vast range of system types and applications in building conditioning. This paper primarily reviews the literature on heat pumps, the various types, and the consideration of design end uses. The fact that there are different energy sources for heat pumps is considered, as well as the different sinks in which energy is stored or dissipated. It is evident that advanced heat pump systems cater well to the use of renewable energy resources. Therefore, in the move towards net-zero energy building operation, the correct selection of a heat pump can help to increase self-consumption of solar PV generation and even make use of direct solar energy heating. This paper reviews the technologies for heat pump selection, application, and design for residential buildings.
BIM Applications in Post-Conflict Contexts: The Reconstruction of Mosul City
Authors: Saeed Zaid O. , Almukhtar Avar , Abanda Henry , Tah Joseph
Published: August 2021

Post-conflict reconstruction has been one of the most challenging themes for the AEC industry, urban designers and planners, and related decision-makers, especially in complex urban contexts with severe destruction in terms of infrastructure. The city of Mosul in Iraq is a case where there is an urgent need for reconstruction, in particular the housing sector after the enormous destruction caused by the ISIS war of 2014–2017. Today, advanced technologies in construction present opportunities to address post-conflict reconstruction challenges. BIM has been used in recent years since it is an integrated and effective process for planning, monitoring and managing contemporary construction projects. Nevertheless, BIM has not been investigated properly in planning and managing post-conflict reconstruction, especially in developing countries. This paper discusses the potential of adopting BIM in post-conflict reconstruction through investigating the validity of the BIM process in planning and assessing possible housing solutions for the reconstruction of Mosul city, using BIM applications. The main findings suggest that BIM applications present significant potential in the process of planning, assessing and managing the reconstruction of post-conflict contexts in developing countries, where conventional methods are limited, dysfunctional and inefficient.
Evaluating the Indoor Air Quality after Renovation at the Greens in Dubai, United Arab Emirates
Authors: Awad Jihad , Jung Chuloh
Published: August 2021

The Public Health and Safety Department of Dubai Municipality had evaluated the indoor air quality in public buildings in 2013, then established the IAQ (Indoor Air Quality) regulation. Even though IAQ in public building is in control, indoor air pollution in new and renovated housing is still very problematic. The objective of this paper is to measure the indoor air quality of the residential unit in an apartment after renovation to evaluate the actual condition and to analyze the influential factors. As a methodology, field measurements, resident interviews, and observations were conducted for 20 residential units to investigate basic information, renovation contents, ventilation characteristics, and SBS (Sick Building Syndrome) symptoms. The results showed that renovation related to the indoor air quality was the replacement of finishing materials. It was statistically proven that the average CO2 for each house was 683–2309.4 ppm, and 15 houses exceeded the WHO IAQ standards. TVOC had an average concentration of 0–3.0 ppm per house, exceeding the standard in 10 houses. Formaldehyde (CH2O) had an average concentration of 0–1.02 ppm per house, exceeding the WHO IAQ standard (0.1 ppm) in 12 houses. However, even though the indoor air quality was polluted, the residents were hardly aware of it based on subjective response survey. As the amount of renovation increases, the concentration of formaldehyde (CH2O) increases significantly, and excessive renovation should be avoided. This study will serve as a basic dataset to suggest that the new IAQ regulation not be compulsory for residents; rather, they must induce contractors with stipulation to maintain IAQ during and after renovation.
A Novel Urine Exosomal lncRNA Assay to Improve the Detection of Prostate Cancer at Initial Biopsy: A Retrospective Multicenter Diagnostic Feasibility Study
Authors: Li Yun , Ji Jin , Lyu Ji , Jin Xin , He Xing , Mo Shaojia , Xu Huan , He Jingyi , Cao Zhi , Chen Xi , Xu Yalong , Wang Lei , Wang Fubo
Published: August 2021

Purpose: This study aimed at developing and validating a novel noninvasive urinary exosome-based post-DRE (digital rectal examination) lncRNA assay to diagnose PCa (prostate cancer) and clinically significant PCa (Gleason score ≥ 7) from the initial prostate biopsy. Methods: A total of 602 urine samples from eligible participants were collected. The expression levels of urinary exosomal PCA3 (prostate cancer antigen 3) and MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) were detected by qPCR (quantitative real-time PCR). Receiver operating characteristic (ROC) analysis was applied to evaluate the diagnostic performance of PCA3, MALAT1 and the lncRNA assay. A decision curve analysis (DCA) and waterfall plots were used to assess the clinical value of the lncRNA assay. Results: Urinary exosomal PCA3 and MALAT1 were overexpressed in PCa and clinically significant PCa (p < 0.001). The lncRNA assay combining PCA3 and MALAT1 had a better diagnostic performance (AUC 0.828) than the current clinical parameters in detecting PCa. More importantly, the lncRNA assay yielded an AUC of 0.831 to detect clinically significant PCa, which is much higher than that of the current clinical parameters. The lncRNA assay was superior to PSA, f/tPSA and the base model for detecting PCa and clinically significant PCa, with a higher net benefit for almost all threshold probabilities. At the cutoff value of 95% sensitivity, the lncRNA assay could avoid 24.2% unnecessary biopsies while only missing 1.2% of the cases of clinically significant PCa. Conclusion: We developed and validated a novel noninvasive post-DRE urine-based lncRNA assay that presented good diagnostic power and clinical utility for the early diagnosis of PCa and high-grade PCa.
The Dimeric Form of HPV16 E6 Is Crucial to Drive YAP/TAZ Upregulation through the Targeting of hScrib
Authors: Messa Lorenzo , Celegato Marta , Bertagnin Chiara , Mercorelli Beatrice , Alvisi Gualtiero , Banks Lawrence , Palù Giorgio , Loregian Arianna
Published: August 2021

Human papillomavirus is the most common viral infectious agent responsible for cancer development in humans. High-risk strains are known to induce cancer through the expression of the viral oncogenes E6 and E7, yet we have only a partial understanding of the precise mechanisms of action of these viral proteins. Here we investigated the molecular mechanism through which the oncoprotein E6 alters the Hippo-YAP/TAZ pathway to trigger YAP/TAZ induction in cancer cells. By employing E6 overexpression systems combined with protein–protein interaction studies and loss-of-function approaches, we discovered that the E6-mediated targeting of hScrib, which supports YAP/TAZ upregulation, intimately requires E6 homodimerization. We show that the self-association of E6, previously reported only in vitro, takes place in the cytoplasm and, as a dimer, E6 targets the fraction of hScrib at the cell cortex for proteasomal degradation. Thus, E6 homodimerization emerges as an important event in the mechanism of E6-mediated hScrib targeting to sustain downstream YAP/TAZ upregulation, unraveling for the first time the key role of E6 homodimerization in the context of its transforming functions and thus paving the way for the possible development of E6 dimerization inhibitors.
Causes and Consequences of HPV Integration in Head and Neck Squamous Cell Carcinomas: State of the Art
Authors: Balaji Harini , Demers Imke , Wuerdemann Nora , Schrijnder Julia , Kremer Bernd , Klussmann Jens Peter , Huebbers Christian Ulrich , Speel Ernst-Jan Maria
Published: August 2021

A constantly increasing incidence in high-risk Human Papillomaviruses (HPV)s driven head and neck squamous cell carcinomas (HNSCC)s, especially of oropharyngeal origin, is being observed. During persistent infections, viral DNA integration into the host genome may occur. Studies are examining if the physical status of the virus (episomal vs. integration) affects carcinogenesis and eventually has further-reaching consequences on disease progression and outcome. Here, we review the literature of the most recent five years focusing on the impact of HPV integration in HNSCCs, covering aspects of detection techniques used (from PCR up to NGS approaches), integration loci identified, and associations with genomic and clinical data. The consequences of HPV integration in the human genome, including the methylation status and deregulation of genes involved in cell signaling pathways, immune evasion, and response to therapy, are also summarized.
Dietary and Genetic Cholesterol Loading Rather Than Steatosis Promotes Liver Tumorigenesis and NASH-Driven HCC
Authors: Ribas Vicent , Conde de la Rosa Laura , Robles David , Núñez Susana , Segalés Paula , Insausti-Urkia Naroa , Solsona-Vilarrasa Estel , Fernández-Checa José , García-Ruiz Carmen
Published: August 2021

The association of nonalcoholic steatohepatitis (NASH) with obesity and type 2 diabetes is a major determinant factor for the continued rise of NASH-driven HCC. Unfortunately, the mechanisms underlying the progression from NASH to HCC are not well-understood. Steatosis is characterized by the accumulation of different lipid species, and cholesterol has emerged as an important player in NASH development, which has been shown to promote NASH-driven HCC. However, recent findings indicated a tumor suppressor role of cholesterol in liver carcinogenesis and HCC development. Thus, we examined the contribution of hepatic steatosis with or without cholesterol accumulation induced by dietary or genetic approaches in liver tumorigenesis and whether the role of cholesterol in NASH-driven HCC is species-dependent. While diethylnitrosamine (DEN) treatment to rats or mice fed a choline-deficient diet decreased the hepatic steatosis, feeding an atherogenic diet enriched in cholesterol potentiated the liver tumor markers. Similar effects were observed in DEN-treated transgenic SREBP-2 mice but not wild-type (WT) mice fed a regular chow diet. Remarkably, long-term feeding of a high-fat high-cholesterol diet (HFHC) but not a high-fat diet (HFD) to WT mice caused severe NASH with spontaneous progression to HCC. A similar outcome was observed in MUP-uPA transgenic mice fed a HFHC diet, which resulted in increased liver tumors and expression of the genes involved in the immune checkpoints. Ezetimibe treatment ameliorated chronic liver disease and, more importantly, tumor multiplicity in HFHC-fed MUP-uPA mice or DEN-treated WT mice. Thus, these results revealed a differential role of steatosis and cholesterol in NASH-driven HCC and indicated that the tumor-promoter role of cholesterol is species-independent and associated with impaired immunosurveillance.
Midterm MRI Follow-Up of Untreated Enchondroma and Atypical Cartilaginous Tumors in the Long Bones
Authors: Deckers Claudia , Rooy Jacky W. J. de , Flucke Uta , Schreuder H. W. Bart , Dierselhuis Edwin F. , Geest Ingrid C. M. van der
Published: August 2021

Management of atypical cartilaginous tumors (ACTs) in the long bones is shifting towards active surveillance to avoid unnecessary surgeries. The frequency and duration of active surveillance for these tumors is unclear as there is little knowledge of its biological behavior. In this retrospective study, we examined the natural course of enchondroma and ACTs through active surveillance. A total of 128 central cartilaginous tumors, located in the long bones, with a minimum interval of 24 months between baseline and last MRI were included. MRI characteristics (e.g., size, scalloping, fat entrapment) were scored and tumors were classified according to the changes between MRIs. Mean follow-up of this study was 50 months, range = 25–138 months. The majority of the cartilaginous tumors (87%) remained stable (n = 65) or showed regression (n = 46) on MRI. A total of 87% of the cases that developed tumor regression presented with entrapped fat at diagnosis. Only 13% (n = 17) showed some progression on MRI, although none of the tumors developed characteristics of high-grade chondrosarcoma. Based on our results, active surveillance is considered safe for enchondroma and ACTs of the long bones. We propose active surveillance for all asymptomatic enchondroma or ACTs in the long bones irrespective of tumor size, and follow-up schemes should be tailored on natural course.
Molecularly Targeted Therapies for Gastric Cancer. State of the Art
Authors: Reddavid Rossella , Dagatti Simona , Franco Caterina , Puca Lucia , Tomatis Mariano , Corso Simona , Giordano Silvia , Degiuli Maurizio
Published: August 2021

Many phase III trials failed to demonstrate a survival benefit from the addition of molecular therapy to conventional chemotherapy for advanced and metastatic gastric cancer, and only three agents were approved by the FDA. We examined the efficacy and safety of novel drugs recently investigated. PubMed, Embase and Cochrane Library were searched for phase III randomized controlled trials published from January 2016 to December 2020. Patients in the experimental arm received molecular therapy with or without conventional chemotherapy, while those in the control arm had conventional chemotherapy alone. The primary outcomes were overall and progression-free survival. The secondary outcomes were the rate of tumor response, severe adverse effects, and quality of life. Eight studies with a total of 4223 enrolled patients were included. The overall and progression-free survival of molecular and conventional therapy were comparable. Most of these trials did not find a significant difference in tumor response rate and in the number of severe adverse effects and related deaths between the experimental and control arms. The survival benefits of molecular therapies available to date for advanced and metastatic gastric cancer are rather unclear, mostly due to inaccurate patient selection, particularly concerning oncogene amplification and copy number.
Smart Modification on Magnetic Nanoparticles Dramatically Enhances Their Therapeutic Properties
Authors: Lafuente-Gómez Nuria , Milán-Rois Paula , García-Soriano David , Luengo Yurena , Cordani Marco , Alarcón-Iniesta Hernán , Salas Gorka , Somoza Álvaro
Published: August 2021

Magnetic nanoparticles (MNP) are employed as nanocarriers and in magnetic hyperthermia (MH) for the treatment of cancers. Herein, a smart drug delivery system composed of MNP functionalized with the cytotoxic drug gemcitabine (MNP-GEM) has been thoroughly evaluated. The linker employed is based on a disulfide bond and allows the controlled release of GEM under a highly reducing environment, which is frequently present in the cytoplasm of tumor cells. The stability, MH, and the interaction with plasma proteins of the nanoparticles are evaluated, highlighting their great potential for biological applications. Their cytotoxicity is assessed in three pancreatic cancer cell lines with different sensitivity to GEM, including the generation of reactive oxygen species (ROS), the effects on the cell cycle, and the mechanisms of cell death involved. Remarkably, the proposed nanocarrier is better internalized than unmodified nanoparticles, and it is particularly effective in PANC-1 cells, resistant to GEM, but not in non-tumoral keratinocytes. Additionally, its combination with MH produces a synergistic cytotoxic effect in all cancer cell lines tested. In conclusion, MNP-GEM presents a promising potential for treating pancreatic cancer, due to multiple parameters, such as reduced binding to plasma proteins, increased internalization, and synergistic activity when combined with MH.
Overexpression of miR-20a-5p in Tumor Epithelium Is an Independent Negative Prognostic Indicator in Prostate Cancer—A Multi-Institutional Study
Authors: Stoen Maria J. , Andersen Sigve , Rakaee Mehrdad , Pedersen Mona I. , Ingebriktsen Lise M. , Donnem Tom , Lombardi Ana P. G. , Kilvaer Thomas K. , Busund Lill-Tove R. , Richardsen Elin
Published: August 2021

Objective: assessing the prognostic role of miR-20a-5p, in terms of clinical outcome, in a large multi-institutional cohort study. Methods: Tissue microarrays from 535 patients’ prostatectomy specimens were constructed. In situ hybridization was performed to assess the expression level of miR-20a-5p in different tissue subregions: tumor stroma (TS) and tumor epithelium (TE). In vitro analysis was performed on prostate cancer cell lines. Results: A high miR-20a-5p expression was found negatively in association with biochemical failure in TE, TS and TE + TS (p = 0.001, p = 0.003 and p = 0.001, respectively). Multivariable analysis confirmed that high miR-20a-5p expression in TE independently predicts dismal prognosis for biochemical failure (HR = 1.56, 95% CI: 1.10–2.21, p = 0.014). Both DU145 and PC3 cells exhibited increased migration ability after transient overexpression of miR-20a-5p, as well as significant elevation of invasion in DU145 cells. Conclusion: A high miR-20a-5p expression in tumor epithelium is an independent negative predictor for biochemical prostate cancer recurrence.
Predictors of Sentinel Lymph Node Metastasis in Postoperatively Upgraded Invasive Breast Carcinoma Patients
Authors: Yu Chi-Chang , Cheung Yun-Chung , Hsueh Chuen , Chen Shin-Cheh
Published: August 2021

Sentinel lymph node (SLN) biopsy (SLNB) usually need not be simultaneously performed with breast-conserving surgery (BCS) for patients diagnosed with ductal carcinoma in situ (DCIS) by preoperative core needle biopsy (CNB), but must be performed once there is invasive carcinoma (IC) found postoperatively. This study aimed to investigate the factors contributing to SLN metastasis in underestimated IC patients with an initial diagnosis of DCIS by CNB. We retrospectively reviewed 1240 consecutive cases of DCIS by image-guided CNB from January 2010 to December 2017 and identified 316 underestimated IC cases with SLNB. Data on clinical characteristics, radiologic features, and final pathological findings were examined. Twenty-three patients (7.3%) had SLN metastasis. Multivariate analysis indicated that an IC tumor size > 0.5 cm (odds ratio: 3.11, p = 0.033) and the presence of lymphovascular invasion (odds ratio: 32.85, p < 0.0001) were independent risk predictors of SLN metastasis. In the absence of any predictors, the incidence of positive SLNs was very low (2.6%) in the total population and extremely low (1.3%) in the BCS subgroup. Therefore, omitting SLNB may be an acceptable option for patients who initially underwent BCS without risk predictors on final pathological assessment. Further prospective studies are necessary before clinical application.
First Comparison between [18f]-FMISO and [18f]-Faza for Preoperative Pet Imaging of Hypoxia in Lung Cancer
Authors: Thureau Sébastien , Piton Nicolas , Gouel Pierrick , Modzelewski Romain , Dujon Antoine , Baste Jean-Marc , Melki Jean , Rinieri Philippe , Peillon Christophe , Rastelli Olivier , Lequesne Justine , Hapdey Sébastien , Sabourin Jean-Christophe , Bohn Pierre , Vera Pierre
Published: August 2021

Hypoxic areas are typically resistant to treatment. However, the fluorine-18-fluoroazomycin-arabinoside (FAZA) and fluorine 18 misonidazole (FMISO) tracers have never been compared in non small cell lung cancer (NSCLC). This study compares the capability of 18F-FAZA PET/CT with that of 18F-FMISO PET/CT for detecting hypoxic tumour regions in early and locally advanced NSCLC patients. We prospectively evaluated patients who underwent preoperative PET scans before surgery for localised NSCLC (i.e., fluorodeoxyglucose (FDG)-PET, FMISO-PET, and FAZA-PET). The PET data of the three tracers were compared with each other and then compared to immunohistochemical analysis (GLUT-1, CAIX, LDH-5, and HIF1-Alpha) after tumour resection. Overall, 19 patients with a mean age of 68.2 ± 8 years were included. There were 18 lesions with significant uptake (i.e., SUVmax >1.4) for the F-MISO and 17 for FAZA. The mean SUVmax was 3 (±1.4) with a mean volume of 25.8 cc (±25.8) for FMISO and 2.2 (±0.7) with a mean volume of 13.06 cc (±13.76) for FAZA. The SUVmax of F-MISO was greater than that of FAZA (p = 0.0003). The SUVmax of F-MISO shows a good correlation with that of FAZA at 0.86 (0.66–0.94). Immunohistochemical results are not correlated to hypoxia PET regardless of the staining. The two tracers show a good correlation with hypoxia, with FMISO being superior to FAZA. FMISO, therefore, remains the reference tracer for defining hypoxic volumes.
Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML
Authors: Millot Frédéric , Suttorp Meinolf , Ragot Stéphanie , Leverger Guy , Dalle Jean-Hugues , Thomas Caroline , Cheikh Nathalie , Nelken Brigitte , Poirée Marilyne , Plat Geneviève , Versluys Birgitta , Lausen Birgitte , Borisevich Marina
Published: August 2021

Within the International Registry of Childhood Chronic Myeloid Leukemia (CML), we identified 18 patients less than 18 years old at diagnosis of CML who were in the chronic phase and exhibiting a sustained deep molecular response (DMR) to imatinib defined as BCR-ABL1/ABL1 < 0.01% (MR4) for at least two years followed by discontinuation of imatinib. Before discontinuation, the median duration of imatinib was 73.2 months (range, 32–109) and the median duration of MR4 was 46.2 months (range, 23.9–98.6). Seven patients experienced loss of major molecular response (MMR) 4.1 months (range, 1.9–6.4) after stopping and so restarted imatinib. The median molecular follow-up after discontinuation was 51 months (range, 6–100) for the nine patients without molecular relapse. The molecular free remission rate was 61% (95% CI, 38–83%), 56% (95% CI, 33–79%) and 56% (95% CI, 33–79%) at 6, 12 and 36 months, respectively. Six of the seven children who experienced molecular relapse after discontinuation regained DMR (median, 4.7 months; range, 2.5–18) after restarting imatinib. No withdrawal syndrome was observed. In univariate analysis, age, sex, Sokal and ELTS scores, imatinib treatment and DMR durations before discontinuation had no influence on treatment free remission. These data suggest that imatinib can be safely discontinued in children with sustained MR4 for at least two years.
Blood-Based Multi-Cancer Detection Using a Novel Variant Calling Assay (DEEPGENTM): Early Clinical Results
Authors: Ris Frederic , Hellan Minia , Douissard Jonathan , Nieva Jorge J. , Triponez Frederic , Woo Yanghee , Geller David , Buchs Nicolas C. , Buehler Leo , Moenig Stefan , Iselin Christophe E. , Karenovics Wolfram , Petignat Patrick , Lam Giang Thanh , Undurraga Malinervo Manuela , Tuttle Rebecca , Ouellette James , Bose Debashish , Ismail Nael , Toso Christian
Published: August 2021

This is an early clinical analysis of the DEEPGENTM platform for cancer detection. Newly diagnosed cancer patients and individuals with no known malignancy were included in a prospective open-label case-controlled study (NCT03517332). Plasma cfDNA that was extracted from peripheral blood was sequenced and data were processed using machine-learning algorithms to derive cancer prediction scores. A total of 260 cancer patients and 415 controls were included in the study. Overall, sensitivity for all cancers was 57% (95% CI: 52, 64) at 95% specificity, and 43% (95% CI: 37, 49) at 99% specificity. With 51% sensitivity and 95% specificity for all stage 1 cancers, the stage-specific sensitivities trended to improve with higher stages. Early results from this preliminary clinical, prospective evaluation of the DEEPGENTM liquid biopsy platform suggests the platform offers a clinically relevant ability to differentiate individuals with and without known cancer, even at early stages of cancer.
Skeletal Muscle Loss and Octogenarian Status Are Associated with S-1 Adjuvant Therapy Discontinuation and Poor Prognosis after Pancreatectomy
Authors: Tsukagoshi Mariko , Harimoto Norifumi , Araki Kenichiro , Kubo Norio , Watanabe Akira , Igarashi Takamichi , Ishii Norihiro , Yamanaka Takahiro , Hagiwara Kei , Hoshino Kouki , Muranushi Ryo , Yajima Toshiki , Shirabe Ken
Published: August 2021

The efficacy and prognosis of adjuvant chemotherapy for resected pancreatic cancer remain unclear. We investigated the utility and risk factors of S-1 adjuvant chemotherapy in patients with pancreatic cancer undergoing pancreatectomy. This study comprised 80 patients, including 58 patients who received S-1 adjuvant chemotherapy. Skeletal muscle loss was defined using cutoff values of skeletal muscle mass index. In total, 16 (20%) octogenarian patients underwent pancreatectomy. Skeletal muscle loss was present in 56 (70%) patients. The entire course of S-1 adjuvant chemotherapy for 6 months was completed in 33 patients (41%). S-1 adjuvant chemotherapy <6 months was an independent prognostic indicator of poor overall survival. Patients who completed S-1 adjuvant chemotherapy exhibited significantly longer overall and relapse-free survival rates than those did not complete the chemotherapy (p < 0.0001 and p = 0.0003, respectively). Being an octogenarian and skeletal muscle loss were independent variables associated with the discontinuation of S-1 adjuvant chemotherapy. Finally, the S-1 adjuvant chemotherapy rates were 6.3% (1/16) and 28.6% (16/56) in octogenarian patients and those with skeletal muscle loss, respectively. S-1 adjuvant chemotherapy completion was associated with improved prognosis in patients with pancreatic cancer. Skeletal muscle loss and octogenarian status predicted the failure of S-1 adjuvant chemotherapy completion.
Extranodal Extension Predicts Poor Survival Outcomes among Patients with Bladder Cancer
Authors: Liao Yi-An , Chiang Chun-Ju , Lee Wen-Chung , Zhuang Bo-Zhi , Chen Chung-Hsin , Pu Yeong-Shiau
Published: August 2021

Background: Several lymph node-related prognosticators were reported in bladder cancer patients with lymph node involvement and receiving radical cystectomy. However, extranodal extension (ENE) remained a debate to predict outcomes. Methods: A retrospective analysis of 1303 bladder cancer patients receiving radical cystectomy and bilateral pelvic lymph node dissection were identified in the National Taiwan Cancer Registry database from 2011 to 2017. Based on the 304 patients with lymph node involvement, the presence of ENE and major clinical information were recorded and calculated. The overall survival (OS) and cancer-specific survival (CSS) were estimated with Kaplan–Meier analysis and compared using the log-rank test. Hazard ratios (HR) and the associated 95% confidence intervals were calculated in the univariate and stepwise multivariable models. Results: In the multivariable analysis, ENE significantly reduced OS (HR = 1.74, 95% CI 1.09–2.78) and CSS (HR = 1.69, 95% CI 1.01–2.83) more than non-ENE. In contrast, adjuvant chemotherapy was significantly associated with better OS and CSS upon the identification of pathological nodal disease. Conclusions: Reduced OS and CSS outcomes were observed in the pathological nodal bladder cancer patients with ENE compared with those without ENE. After the identification of pathological nodal disease, adjuvant chemotherapy was associated with better survival outcomes.
A Warp-Knitted Light-Emitting Fabric-Based Device for In Vitro Photodynamic Therapy: Description, Characterization, and Application on Human Cancer Cell Lines
Authors: Thécua Elise , Ziane Laurine , Grolez Guillaume Paul , Fagart Alexandre , Kumar Abhishek , Leroux Bertrand , Baert Gregory , Deleporte Pascal , Vermandel Maximilien , Vignion-Dewalle Anne-Sophie , Delhem Nadira , Mordon Serge
Published: August 2021

Photodynamic therapy (PDT) appears to be a promising strategy in biomedical applications. However, the complexity of its parameters prevents wide acceptance. This work presents and characterizes a novel optical device based on knitted light-emitting fabrics and dedicated to in vitro PDT involving low irradiance over a long illumination period. Technical characterization of this device, called CELL-LEF, is performed. A cytotoxic study of 5-ALA-mediated PDT on human cancer cell lines is provided as a proof of concept. The target of delivering an irradiance of 1 mW/cm2 over 750 cm2 is achieved (mean: 0.99 mW/cm2; standard deviation: 0.13 mW/cm2). The device can maintain a stable temperature with the mean thermal distribution of 35.1 °C (min: 30.7 °C; max: 38.4 °C). In vitro outcomes show that 5-ALA PDT using CELL-LEF consistently and effectively induced a decrease in tumor cell viability: Almost all the HepG2 cells died after 80 min of illumination, while less than 60% of U87 cell viability remained. CELL-LEF is suitable for in vitro PDT involving low irradiance over a long illumination period.
MicroRNAs as Potential Predictors of Response to CDK4/6 Inhibitor Treatment
Authors: Andrikopoulou Angeliki , Shalit Almog , Zografos Eleni , Koutsoukos Konstantinos , Korakiti Anna-Maria , Liontos Michalis , Dimopoulos Meletios-Athanasios , Zagouri Flora
Published: August 2021

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel treatment options in the management of advanced or metastatic breast cancer. MicroRNAs are endogenous non-coding 19–22-nucleotide-long RNAs that regulate gene expression in development and tumorigenesis. Herein, we systematically review all microRNAs associated with response to CDK4/6 inhibitors in solid tumors and hematological malignancies. Eligible articles were identified by a search of the MEDLINE and ClinicalTrials.gov databases for the period up to1 January 2021; the algorithm consisted of a predefined combination of the words “microRNAs”, “cancer” and “CDK 4/6 inhibitors”. Overall, 15 studies were retrieved. Six microRNAs (miR-126, miR-326, miR3613-3p, miR-29b-3p, miR-497 and miR-17-92) were associated with sensitivity to CDK4/6 inhibitors. Conversely, six microRNAs (miR-193b, miR-432-5p, miR-200a, miR-223, Let-7a and miR-21) conferred resistance to treatment with CDK4/6 inhibitors. An additional number of microRNAs (miR-124a, miR9, miR200b and miR-106b) were shown to mediate cellular response to CDK4/6 inhibitors without affecting sensitivity to treatment. Collectively, our review provides evidence that microRNAs could serve as predictive biomarkers for treatment with CDK4/6 inhibitors. Moreover, microRNA-targeted therapy could potentially maximize sensitivity to CDK4/6 inhibition.
Catalyst and Elemental Analysis Involving Biodiesel from Various Feedstocks
Authors: Simbi Ines , Aigbe Uyiosa Osagie , Oyekola Oluwaseun , Osibote Otolorin Adelaja
Published: August 2021

The world is currently faced with the depletion of fossil fuel energy sources and their use is associated with environmental pollution. This has triggered the need to seek alternative energy sources that are renewable, sustainable and environmentally benign. Biodiesel, an alternative fuel of interest, is obtainable from biomass feedstocks. In existing biodiesel fuel, there are concerns that it is a contaminant due to its elemental contents, which over time also affect its quality. This study aimed to investigate the influence of a bifunctional catalyst on the conversion of free fatty acids and the elemental composition of biodiesel obtained from waste oils of sunflower and palm feedstocks. The synthesised catalyst was characterised using BET, XRD, FTIR and SEM while ICP-OES and Rancimat were used for elemental contents and oxidation in feedstocks and biodiesels. The effect of Cu, Zn and Fe metals on the stability of synthesised biodiesel was further studied. The catalyst showed characteristics of bifunctionality with improved textural properties necessary for the conversion of high free fatty acids feedstocks to biodiesel, despite increasing Ca content within the produced biodiesel. Sunflower biodiesel showed superior fuel quality, although palm biodiesel had more oxidation stability. An increase in the concentration of metals decreased the induction period, with Cu and Fe being more effective than Zn metal.
Acenaphthene-Based N-Heterocyclic Carbene Metal Complexes: Synthesis and Application in Catalysis
Authors: Baczewska Paulina , Śniady Katarzyna , Kośnik Wioletta , Michalak Michał
Published: August 2021

N-Heterocyclic carbene (NHC) ligands have become a privileged structural motif in modern homogenous and heterogeneous catalysis. The last two decades have brought a plethora of structurally and electronically diversified carbene ligands, enabling the development of cutting-edge transformations, especially in the area of carbon-carbon bond formation. Although most of these were accomplished with common imidazolylidene and imidazolinylidene ligands, the most challenging ones were only accessible with the acenaphthylene-derived N-heterocyclic carbene ligands bearing a π-extended system. Their superior σ-donor capabilities with simultaneous ease of modification of the rigid backbone enhance the catalytic activity and stability of their transition metal complexes, which makes BIAN-NHC (BIAN—bis(imino)acenaphthene) ligands an attractive tool for the development of challenging reactions. The present review summarizes synthetic efforts towards BIAN-NHC metal complexes bearing acenaphthylene subunits and their applications in modern catalysis, with special emphasis put on recently developed enantioselective processes.
Photo-Oxidation of Ammonia to Molecular Nitrogen in Water under UV, Vis and Sunlight Irradiation
Authors: Conte Francesco , Pellegatta Veronica , Tripodi Antonio , Ramis Gianguido , Rossetti Ilenia
Published: August 2021

Titanium dioxide-based photocatalysts have been used to perform the photo-oxidation of ammonium/ammonia to molecular nitrogen. Different light sources were employed, i.e., UV, LED visible light and natural sunlight, and their performance was compared in order to understand which setup was the most efficient. It was found that under selected conditions, the LED lamp, in combination with silver-promoted TiO2, was able to push the conversion of ammonium toward 48% after 4 h of reaction time. On the other hand, with a more powerful UV lamp, lower conversion was achieved, ca. 40%. Natural sunlight under the same conditions attained more than 38% conversion, but the fluctuation of the reaction conditions remain a very critical issue for the real exploitation of sunlight in water treatment.
Gut Microbiota and Neuroplasticity
Authors: Murciano-Brea Julia , Garcia-Montes Martin , Geuna Stefano , Herrera-Rincon Celia
Published: August 2021

The accumulating evidence linking bacteria in the gut and neurons in the brain (the microbiota–gut–brain axis) has led to a paradigm shift in the neurosciences. Understanding the neurobiological mechanisms supporting the relevance of actions mediated by the gut microbiota for brain physiology and neuronal functioning is a key research area. In this review, we discuss the literature showing how the microbiota is emerging as a key regulator of the brain’s function and behavior, as increasing amounts of evidence on the importance of the bidirectional communication between the intestinal bacteria and the brain have accumulated. Based on recent discoveries, we suggest that the interaction between diet and the gut microbiota, which might ultimately affect the brain, represents an unprecedented stimulus for conducting new research that links food and mood. We also review the limited work in the clinical arena to date, and we propose novel approaches for deciphering the gut microbiota–brain axis and, eventually, for manipulating this relationship to boost mental wellness.
Radiation-Induced Overexpression of TGFβ and PODXL Contributes to Colorectal Cancer Cell Radioresistance through Enhanced Motility
Authors: Lee Hyunjung , Kong Joon-Seog , Lee Seung-Sook , Kim Areumnuri
Published: August 2021

The primary cause of colorectal cancer (CRC) recurrence is increased distant metastasis after radiotherapy, so there is a need for targeted therapeutic approaches to reduce the metastatic-relapse risk. Dysregulation of the cell-surface glycoprotein podocalyxin-like protein (PODXL) plays an important role in promoting cancer-cell motility and is associated with poor prognoses for many malignancy types. We found that CRC cells exposed to radiation demonstrated increased TGFβ and PODXL expressions, resulting in increased migration and invasiveness due to increased extracellular matrix deposition. In addition, both TGFβ and PODXL were highly expressed in tissue samples from radiotherapy-treated CRC patients compared to those from patients without this treatment. However, it is unclear whether TGFβ and PODXL interactions are involved in cancer-progression resistance after radiation exposure in CRC. Here, using CRC cells, we showed that silencing PODXL blocked radiation-induced cell migration and invasiveness. Cell treatment with galunisertib (a TGFβ-pathway inhibitor) also led to reduced viability and migration, suggesting that its clinical use may enhance the cytotoxic effects of radiation and lead to the effective inhibition of CRC progression. Overall, the results demonstrate that downregulation of TGFβ and its-mediated PODXL may provide potential therapeutic targets for patients with radiotherapy-resistant CRC.
Immobilization of Jagged1 Enhances Vascular Smooth Muscle Cells Maturation by Activating the Notch Pathway
Authors: Zohorsky Kathleen , Lin Shigang , Mequanint Kibret
Published: August 2021

In Notch signaling, the Jagged1-Notch3 ligand-receptor pairing is implicated for regulating the phenotype maturity of vascular smooth muscle cells. However, less is known about the role of Jagged1 presentation strategy in this regulation. In this study, we used bead-immobilized Jagged1 to direct phenotype control of primary human coronary artery smooth muscle cells (HCASMC), and to differentiate embryonic multipotent mesenchymal progenitor (10T1/2) cell towards a vascular lineage. This Jagged1 presentation strategy was sufficient to activate the Notch transcription factor HES1 and induce early-stage contractile markers, including smooth muscle α-actin and calponin in HCASMCs. Bead-bound Jagged1 was unable to regulate the late-stage markers myosin heavy chain and smoothelin; however, serum starvation and TGFβ1 were used to achieve a fully contractile smooth muscle cell. When progenitor 10T1/2 cells were used for Notch3 signaling, pre-differentiation with TGFβ1 was required for a robust Jagged1 specific response, suggesting a SMC lineage commitment was necessary to direct SMC differentiation and maturity. The presence of a magnetic tension force to the ligand-receptor complex was evaluated for signaling efficacy. Magnetic pulling forces downregulated HES1 and smooth muscle α-actin in both HCASMCs and progenitor 10T1/2 cells. Taken together, this study demonstrated that (i) bead-bound Jagged1 was sufficient to activate Notch3 and promote SMC differentiation/maturation and (ii) magnetic pulling forces did not activate Notch3, suggesting the bead alone was able to provide necessary clustering or traction forces for Notch activation. Notch is highly context-dependent; therefore, these findings provide insights to improve biomaterial-driven Jagged1 control of SMC behavior.
Insulin Sensitivity Is Retained in Mice with Endothelial Loss of Carcinoembryonic Antigen Cell Adhesion Molecule 1
Authors: Muturi Harrison T. , Khuder Saja S. , Ghadieh Hilda E. , Esakov Emily L. , Noh Hyelim , Kang Heejoon , McInerney Marcia F. , Kim Jason K. , Lee Abraham D. , Najjar Sonia M.
Published: August 2021

CEACAM1 regulates endothelial barrier integrity. Because insulin signaling in extrahepatic target tissues is regulated by insulin transport through the endothelium, we aimed at investigating the metabolic role of endothelial CEACAM1. To this end, we generated endothelial cell-specific Ceacam1 null mice (VECadCre+Cc1fl/fl) and carried out their metabolic phenotyping and mechanistic analysis by comparison to littermate controls. Hyperinsulinemic-euglycemic clamp analysis showed intact insulin sensitivity in VECadCre+Cc1fl/fl mice. This was associated with the absence of visceral obesity and lipolysis and normal levels of circulating non-esterified fatty acids, leptin, and adiponectin. Whereas the loss of endothelial Ceacam1 did not affect insulin-stimulated receptor phosphorylation, it reduced IRS-1/Akt/eNOS activation to lower nitric oxide production resulting from limited SHP2 sequestration. It also reduced Shc sequestration to activate NF-κB and increase the transcription of matrix metalloproteases, ultimately inducing plasma IL-6 and TNFα levels. Loss of endothelial Ceacam1 also induced the expression of the anti-inflammatory CEACAM1-4L variant in M2 macrophages in white adipose tissue. Together, this could cause endothelial barrier dysfunction and facilitate insulin transport, sustaining normal glucose homeostasis and retaining fat accumulation in adipocytes. The data assign a significant role for endothelial cell CEACAM1 in maintaining insulin sensitivity in peripheral extrahepatic target tissues.
The State of Immunotherapy in Hepatobiliary Cancers
Authors: Ilyas Farhan Z. , Beane Joal D. , Pawlik Timothy M.
Published: August 2021

Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials. In advanced CCA and GBC, PD-1 ICIs have resulted in antitumor responses, but only in a minority of select patients. Other ICIs are being investigated for patients with CCA and GBC. Adoptive transfer may hold promise, with reports of complete durable regression in metastatic CCA, yet this therapeutic approach may not be generalizable. Alternative approaches have been developed and promising results have been observed, but clinical trials are needed to validate their utility. While the treatment of hepatobiliary cancers involves unique challenges that these cancers present, the progress seen with ICIs and adoptive transfer has solidified immunotherapy as an important approach in these challenging patients with few other effective treatment options.
Type 1 Diabetes and Addison’s Disease: When the Diagnosis Is Suggested by the Continuous Glucose Monitoring System
Authors: Vinci Francesco , d’Annunzio Giuseppe , Napoli Flavia , Bassi Marta , Montobbio Carolina , Ferrando Giulia , Minuto Nicola
Published: August 2021

Our objective is to emphasize the important role of continuous glucose monitoring (CGM) in suggesting adrenal insufficiency in patients affected by type 1 diabetes. We describe an adolescent girl with type 1 diabetes and subsequent latent Addison’s disease diagnosed based on a recurrent hypoglycemic trend detected by CGM. In patients with type 1 diabetes, persistent unexplained hypoglycemic episodes at dawn together with reduced insulin requirement arouse souspicionof adrenal insufficiency. Adrenal insufficiency secondary to autoimmune Addison’s disease, even if rarely encountered among young patients, may be initially symptomless and characterized by slow progression up to acute adrenal crisis, which represents a potentially life-threatening condition. Besides glycometabolic assessment and adequate insulin dosage adjustment, type 1 diabetes needs prompt recognition of potentially associated autoimmune conditions. Among these, Addison’s disease can be suspected, although latent or paucisymptomatic, through periodic and careful evaluation of CGM data.
Functionalized Carbon Nanotubes for Chemical Sensing: Electrochemical Detection of Hydrogen Isotopes
Authors: Iordache Stefan-Marian , Ionete Eusebiu Ilarian , Iordache Ana-Maria , Stamatin Ioan , Zoita Nicolae Catalin , Sobetkii Arcadie , Grigorescu Cristiana Eugenia Ana
Published: August 2021

In this study, we propose a palladium-functionalized CNT composite working as a sensitive material to evaluate the deuterium concentration in aqueous samples. The sensitive material was prepared by the deposition of Pd nanoparticles onto MWCNT–OH by the micellization process. A modified electrode was prepared by drop casting 60 μL of Pd-decorated MWCNT suspension on a clean glassy carbon electrode surface. The sensing behavior was investigated in a series of deuterium-enriched solutions ranging from 25 to 10,000 ppm. We performed cyclic voltammetry and impedance spectroscopy studies on the samples. The process is quasi-reversible with the reduction curve more pronounced than the oxidation curve, which indicates a low tendency to desorption for the hydrogen atoms.
A Study on Solution-Processed Y2O3 Films Modified by Atomic Layer Deposition Al2O3 as Dielectrics in ZnO Thin Film Transistor
Authors: Xu Haiyang , Ding Xingwei , Qi Jie , Yang Xuyong , Zhang Jianhua
Published: August 2021

In this work, Y2O3–Al2O3 dielectrics were prepared and used in ZnO thin film transistor as gate insulators. The Y2O3 film prepared by the sol–gel method has many surface defects, resulting in a high density of interface states with the active layer in TFT, which then leads to poor stability of the devices. We modified it by atomic layer deposition (ALD) technology that deposited a thin Al2O3 film on the surface of a Y2O3 dielectric layer, and finally fabricated a TFT device with ZnO as the active layer by ALD. The electrical performance and bias stability of the ZnO TFT with a Y2O3–Al2O3 laminated dielectric layer were greatly improved, the subthreshold swing was reduced from 147 to 88 mV/decade, the on/off-state current ratio was increased from 4.24 × 106 to 4.16 × 108, and the threshold voltage shift was reduced from 1.4 to 0.7 V after a 5-V gate was is applied for 800 s.