bluuebunny/crossref_metadata_2025 huggingface dataset:
Markers of Genetic Variation in Blue Gourami (Trichogaster trichopterus) as a Model for Labyrinth Fish
Authors: Degani Gad , Veksler-Lublinsky Isana , Meerson Ari
Published: March 2021

Markers of genetic variation between species are important for both applied and basic research. Here, various genes of the blue gourami (Trichogaster trichopterus, suborder Anabantoidei, a model labyrinth fish), many of them involved in growth and reproduction, are reviewed as markers of genetic variation. The genes encoding the following hormones are described: kisspeptins 1 and 2, gonadotropin-releasing hormones 1, 2, and 3, growth hormone, somatolactin, prolactin, follicle- stimulating hormone and luteinizing hormone, as well as mitochondrial genes encoding cytochrome b and 12S rRNA. Genetic markers in blue gourami, representing the suborder Anabantoidei, differ from those in other bony fishes. The sequence of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene of blue gourami is often used to study the Anabantoidei suborder. Among the genes involved in controlling growth and reproduction, the most suitable genetic markers for distinguishing between species of the Anabantoidei have functions in the hypothalamic–pituitary–somatotropic axis: pituitary adenylate cyclase-activating polypeptide and growth hormone, and the 12S rRNA gene.
Peptide Dendrimers with Non-Symmetric Bola Structure Exert Long Term Effect on Glioblastoma and Neuroblastoma Cell Lines
Authors: Sowińska Marta , Szeliga Monika , Morawiak Maja , Ziemińska Elżbieta , Zabłocka Barbara , Urbańczyk-Lipkowska Zofia
Published: March 2021

Background: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system (CNS). Neuroblastoma (NB) is one of the most common cancers of childhood derived from the neural crest cells. The survival rate for patients with GBM and high-risk NB is poor; therefore, novel therapeutic approaches are needed. Increasing evidence suggests a dual role of redox-active compounds in both tumorigenesis and cancer treatment. Therefore, in this study, polyfunctional peptide-based dendrimeric molecules of the bola structure carrying residues with antiproliferative potential on one side and the antioxidant residues on the other side were designed. Methods: We synthesized non-symmetric bola dendrimers and assessed their radical scavenging potency as well as redox capability. The influence of dendrimers on viability of rat primary cerebellar neurons (CGC) and normal human astrocytes (NHA) was determined by propidium iodide staining and cell counting. Cytotoxicity against human GBM cell lines, T98G and LN229, and NB cell line SH-SY5Y was assessed by cell counting and colony forming assay. Results: Testing of CGC and NHA viability allowed to establish a range of optimal dendrimers structure and concentration for further evaluation of their impact on two human GBM and one human NB cell lines. According to ABTS, DPPH, FRAP, and CUPRAC antioxidant tests, the most toxic for normal cells were dendrimers with high charge and an excess of antioxidant residues (Trp and PABA) on both sides of the bola structure. At 5 μM concentration, most of the tested dendrimers neither reduced rat CGC viability below 50–40%, nor harmed human neurons (NHA). The same dose of compounds 16 or 22, after 30 min treatment decreased the number of SH-SY5Y and LN229 cells, but did not affect the number of T98G cells 48 h post treatment. However, either compound significantly reduced the number of colonies formed by SH-SY5Y, LN229, and T98G cells measured 14 days after treatment. Conclusions: Peptide dendrimers with non-symmetric bola structure are excellent scaffolds for design of molecules with pro/antioxidant functionality. Design of molecules with an excess of positive charges and antioxidant residues rendered molecules with high neurotoxicity. Single, 30 min exposition of the GBM and NB cell lines to the selected bola dendrimers significantly suppressed their clonogenic potential
Animal Models for Radiotherapy Research: All (Animal) Models Are Wrong but Some Are Useful
Authors: Butterworth Karl T. , Williams Jacqueline P.
Published: March 2021

The distinguished statistician, George E [...]
Time-to-Treatment in Oral Cancer: Causes and Implications for Survival
Authors: Saka-Herrán Constanza , Jané-Salas Enric , Mari-Roig Antoni , Estrugo-Devesa Albert , López-López José
Published: March 2021

The purpose of this review was to identify and describe the causes that influence the time-intervals in the pathway of diagnosis and treatment of oral cancer and to assess its impact on prognosis and survival. The review was structured according to the recommendations of the Aarhus statement, considering original data from individual studies and systematic reviews that reported outcomes related to the patient, diagnostic and pre-treatment intervals. The patient interval is the major contributor to the total time-interval. Unawareness of signs and/or symptoms, denial and lack of knowledge about oral cancer are the major contributors to the process of seeking medical attention. The diagnostic interval is influenced by tumor factors, delays in referral due to higher number of consultations and previous treatment with different medicines or dental procedures and by professional factors such as experience and lack of knowledge related to the disease and diagnostic procedures. Patients with advanced stage disease, primary treatment with radiotherapy, treatment at an academic facility and transitions in care are associated with prolonged pre-treatment intervals. An emerging body of evidence supports the impact of prolonged pre-treatment and treatment intervals with poorer survival from oral cancer.
NFκB-Activated COX2/PGE2/EP4 Axis Controls the Magnitude and Selectivity of BCG-Induced Inflammation in Human Bladder Cancer Tissues
Authors: Ibrahim Omar M. , Basse Per H. , Jiang Weijian , Guru Khurshid , Chatta Gurkamal , Kalinski Pawel
Published: March 2021

Bacillus Calmette-Guérin (BCG) is commonly used in the immunotherapy of bladder cancer (BlCa) but its effectiveness is limited to only a fraction of patients. To identify the factors that regulate the response of human BlCa tumor microenvironment (TME) to BCG, we used the ex vivo whole-tissue explant model. The levels of COX2 in the BCG-activated explants closely correlated with the local production of Treg- and MDSCS attractants and suppressive factors, while the baseline COX2 levels did not have predictive value. Accordingly, we observed that BCG induced high levels of MDSC- and Treg-attracting chemokines (CCL22, CXCL8, CXCL12) and suppressive factors (IDO1, IL-10, NOS2). These undesirable effects were associated with the nuclear translocation of phosphorylated NFκB, induction of COX2, the key enzyme controlling PGE2 synthesis, and elevation of a PGE2 receptor, EP4. While NFκB blockade suppressed both the desirable and undesirable components of BCG-driven inflammation, the inhibitors of PGE2 synthesis (Celecoxib or Indomethacin) or signaling (EP4-selective blocker, ARY-007), selectively eliminated the induction of MDSC/Treg attractants and immunosuppressive factors but enhanced the production of CTL attractants, CCL5, CXCL9 and CXCL10. PGE2 blockade allowed for the selectively enhanced migration of CTLs to the BCG-treated BlCa samples and eliminated the enhanced migration of Tregs. Since the balance between the CTLs and suppressive cells in the TME predicts the outcomes in patients with BlCa and other diseases, our data help to elucidate the mechanisms which limit the effectiveness of BCG therapies and identify new targets to enhance their therapeutic effects.
Baseline Characteristics and Outcomes of Cancer Patients Infected with SARS-CoV-2 in the Lombardy Region, Italy (AIOM-L CORONA): A Multicenter, Observational, Ambispective, Cohort Study
Authors: Di Cosimo Serena , Tagliaferri Barbara , Generali Daniele , Giudici Fabiola , Agustoni Francesco , Bernardo Antonio , Borgonovo Karen , Farina Gabriella , Luchena Giovanna , Luciani Andrea , Nolè Franco , Palmeri Laura , Pietrantonio Filippo , Poggi Guido , Zucali Paolo Andrea , Balletti Emanuela , Catania Giovanna , Bernocchi Ottavia , D’Antonio Federica , Giordano Monica , Grossi Francesco , Lasagna Angioletta , La Verde Nicla , Manzoni Mariangela , Montagna Benedetta , Olgiati Angelo , Raimondi Alessandra , Rampinelli Irene , Verri Elena , Zaniboni Alberto , Di Maio Massimo , Beretta Giordano , Danova Marco
Published: March 2021

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years; 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12–218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32–2.15); however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11–0.51, p < 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.
Immune-Stimulatory Effects of Curcumin on the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma
Authors: Kötting Charlotte , Hofmann Linda , Lotfi Ramin , Engelhardt Daphne , Laban Simon , Schuler Patrick J. , Hoffmann Thomas K. , Brunner Cornelia , Theodoraki Marie-Nicole
Published: March 2021

Curcumin is known to have immune-modulatory and antitumor effects by interacting with more than 30 different proteins. An important feature of curcumin is the inhibition of nuclear factor kappa of activated B-cells (NF-κB). Here, we evaluate the potential of curcumin to reverse the epithelial to mesenchymal transition (EMT) of head and neck squamous cell carcinoma (HNSCC) cells as a part of tumor escape mechanisms. We examined the impact of curcumin on the expression of different pro- and antitumoral chemokines in ex vivo HNSCC tumor tissue and primary macrophage cultures. Further, we evaluated the combinatorial effect of curcumin and toll-like receptor 3 (TLR3) agonist Poly I:C (PIC) on NF-κB inhibition and regulatory T-cell (Treg) attraction. Mesenchymal markers were significantly reduced in cancer specimens after incubation with curcumin, with simultaneous reduction of key transcription factors of EMT, Snail, and Twist. Furthermore, a decrease of the Treg-attracting chemokine CCL22 was observed. Additionally, curcumin-related inhibition of NF-κB nuclear translocation was evident. The combination of PIC with curcumin resulted in further NF-κB inhibition, whereas PIC alone contrarily resulted in NF-κB activation. Furthermore, curcumin was more effective in inhibiting PIC-dependent NF-κB activation and Treg attraction compared to known NF-κB inhibitors BAY 11-7082 or caffeic acid phenethyl ester (CAPE). The presented results show, for the first time, the immune-modulating effects of curcumin in HNSCC, with potent inhibition of the Treg-attracting effects of PIC. Hence, curcumin presents a promising drug in cancer therapy as a supplement to already established treatments.
Diagnostic Algorithm for Metastatic Lymph Nodes of Differentiated Thyroid Carcinoma
Authors: Chung Sae Rom , Baek Jung Hwan , Choi Young Jun , Sung Tae-Yon , Song Dong Eun , Kim Tae Yong , Lee Jeong Hyun
Published: March 2021

We aimed to evaluate appropriate strategies for interpreting fine-needle aspiration cytology (FNAC) and thyroglobulin concentrations obtained through aspiration (FNA-Tg) results based on the sonographic features of lymph nodes (LNs). Consecutive patients who underwent ultrasound-guided FNAC and FNA-Tg for metastatic LNs from differentiated thyroid carcinomas (DTCs) from January 2014 to December 2018 were reviewed retrospectively. LNs were categorized sonographically as suspicious, indeterminate, or benign. The optimal FNA-Tg cutoff for metastatic LNs was evaluated preoperatively, after lobectomy, and after total thyroidectomy. The diagnostic performances of FNA-Tg, FNAC, and their combination were analyzed based on the sonographic features of LNs. The malignancy rates of LNs were analyzed based on the sonographic features, FNAC, and FNA-Tg results. Of the 1543 LNs analyzed, 528 were benign, whereas 1015 were malignant. FNA-Tg increased the sensitivity and accuracy of FNAC for LNs. The malignancy rate of LNs found to be malignant by FNAC or elevated FNA-Tg ranged from 82% to 100%, regardless of the sonographic features. The malignancy rate of LNs with indeterminate or benign FNAC findings and low FNA-Tg were stratified according to their sonographic features. We propose a diagnostic algorithm, based on combined FNAC, FNA-Tg, and ultrasound features of LNs, for diagnosing metastatic LNs of DTCs.
Detection of Rare Germline Variants in the Genomes of Patients with B-Cell Neoplasms
Authors: Mosquera Orgueira Adrián , Cid López Miguel , Peleteiro Raíndo Andrés , Díaz Arias José Ángel , Antelo Rodríguez Beatriz , Bao Pérez Laura , Alonso Vence Natalia , Bendaña López Ángeles , Abuin Blanco Aitor , Melero Valentín Paula , Ferreiro Ferro Roi , Aliste Santos Carlos , Fraga Rodríguez Máximo Francisco , González Pérez Marta Sonia , Pérez Encinas Manuel Mateo , Bello López José Luis
Published: March 2021

There is growing evidence indicating the implication of germline variation in cancer predisposition and prognostication. Here, we describe an analysis of likely disruptive rare variants across the genomes of 726 patients with B-cell lymphoid neoplasms. We discovered a significant enrichment for two genes in rare dysfunctional variants, both of which participate in the regulation of oxidative stress pathways (CHMP6 and GSTA4). Additionally, we detected 1675 likely disrupting variants in genes associated with cancer, of which 44.75% were novel events and 7.88% were protein-truncating variants. Among these, the most frequently affected genes were ATM, BIRC6, CLTCL1A, and TSC2. Homozygous or germline double-hit variants were detected in 28 cases, and coexisting somatic events were observed in 17 patients, some of which affected key lymphoma drivers such as ATM, KMT2D, and MYC. Finally, we observed that variants in six different genes were independently associated with shorter survival in CLL. Our study results support an important role for rare germline variation in the pathogenesis and prognosis of B-cell lymphoid neoplasms.
Oral and Intravenous Iron Therapy Differentially Alter the On- and Off-Tumor Microbiota in Anemic Colorectal Cancer Patients
Authors: Phipps Oliver , Al-Hassi Hafid O. , Quraishi Mohammed N. , Dickson Edward A. , Segal Jonathan , Steed Helen , Kumar Aditi , Acheson Austin G. , Beggs Andrew D. , Brookes Matthew J.
Published: March 2021

Iron deficiency anemia is a common complication of colorectal cancer and may require iron therapy. Oral iron can increase the iron available to gut bacteria and may alter the colonic microbiota. We performed an intervention study to compare oral and intravenous iron therapy on the colonic tumor-associated (on-tumor) and paired non-tumor-associated adjacent (off-tumor) microbiota. Anemic patients with colorectal adenocarcinoma received either oral ferrous sulphate (n = 16) or intravenous ferric carboxymaltose (n = 24). On- and off-tumor biopsies were obtained post-surgery and microbial profiling was performed using 16S ribosomal RNA analysis. Off-tumor α- and β-diversity were significantly different between iron treatment groups. No differences in on-tumor diversity were observed. Off-tumor microbiota of oral iron-treated patients showed higher abundances of the orders Clostridiales, Cytophagales, and Anaeroplasmatales compared to intravenous iron-treated patients. The on-tumor microbiota was enriched with the orders Lactobacillales and Alteromonadales in the oral and intravenous iron groups, respectively. The on- and off-tumor microbiota associated with intravenous iron-treated patients infers increased abundances of enzymes involved in iron sequestration and anti-inflammatory/oncogenic metabolite production, compared to oral iron-treated patients. Collectively, this suggests that intravenous iron may be a more appropriate therapy to limit adverse microbial outcomes compared to oral iron.
The Fusion Gene Landscape in Taiwanese Patients with Non-Small Cell Lung Cancer
Authors: Chang Ya-Sian , Tu Siang-Jyun , Yen Ju-Chen , Lee Ya-Ting , Fang Hsin-Yuan , Chang Jan-Gowth
Published: March 2021

Background: Analyzing fusion gene transcripts may yield an effective approach for selecting cancer treatments. However, few comprehensive analyses of fusions in non-small cell lung cancer (NSCLC) patients have been performed. Methods: We enrolled 54 patients with NSCLC, and performed RNA-sequencing (RNA-Seq). STAR (Spliced Transcripts Alignment to a Reference)-Fusion was used to identify fusions. Results: Of the 218 fusions discovered, 24 had been reported and the rest were novel. Three fusions had the highest occurrence rates. After integrating our gene expression and fusion data, we found that samples harboring fusions containing ASXL1, CACNA1A, EEF1A1, and RET also exhibited increased expression of these genes. We then searched for mutations and fusions in cancer driver genes in each sample and found that nine patients carried both mutations and fusions in cancer driver genes. Furthermore, we found a trend for mutual exclusivity between gene fusions and mutations in the same gene, with the exception of DMD, and we found that EGFR mutations are associated with the number of fusion genes. Finally, we identified kinase gene fusions, and potentially druggable fusions, which may play roles in lung cancer therapy. Conclusion: The clinical use of RNA-Seq for detecting driver fusion genes may play an important role in the treatment of lung cancer.
Heterogeneity in Signaling Pathway Activity within Primary and between Primary and Metastatic Breast Cancer
Authors: Inda Márcia A. , van Swinderen Paul , van Brussel Anne , Moelans Cathy B. , Verhaegh Wim , van Zon Hans , den Biezen Eveline , Bikker Jan Willem , van Diest Paul J. , van de Stolpe Anja
Published: March 2021

Targeted therapy aims to block tumor-driving signaling pathways and is generally based on analysis of one primary tumor (PT) biopsy. Tumor heterogeneity within PT and between PT and metastatic breast lesions may, however, impact the effect of a chosen therapy. Whereas studies are available that investigate genetic heterogeneity, we present results on phenotypic heterogeneity by analyzing the variation in the functional activity of signal transduction pathways, using an earlier developed platform to measure such activity from mRNA measurements of pathways’ direct target genes. Statistical analysis comparing macro-scale variation in pathway activity on up to five spatially distributed PT tissue blocks (n = 35), to micro-scale variation in activity on four adjacent samples of a single PT tissue block (n = 17), showed that macro-scale variation was not larger than micro-scale variation, except possibly for the PI3K pathway. Simulations using a “checkerboard clone-size” model showed that multiple small clones could explain the higher micro-scale variation in activity found for the TGFβ and Hedgehog pathways, and that intermediate/large clones could explain the possibly higher macro-scale variation of the PI3K pathway. While within PT, pathway activities presented a highly positive correlation, correlations weakened between PT and lymph node metastases (n = 9), becoming even worse for PT and distant metastases (n = 9), including a negative correlation for the ER pathway. While analysis of multiple sub-samples of a single biopsy may be sufficient to predict PT response to targeted therapies, metastatic breast cancer treatment prediction requires analysis of metastatic biopsies. Our findings on phenotypic intra-tumor heterogeneity are compatible with emerging ideas on a Big Bang type of cancer evolution in which macro-scale heterogeneity appears not dominant.
Hyperglycemia-Induced miR-467 Drives Tumor Inflammation and Growth in Breast Cancer
Authors: Gajeton Jasmine , Krukovets Irene , Muppala Santoshi , Verbovetskiy Dmitriy , Zhang Jessica , Stenina-Adognravi Olga
Published: March 2021

The tumor microenvironment contains the parenchyma, blood vessels, and infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs affect the developing tumor and drive cancer inflammation. We used mouse models of hyperglycemia and cancer and specimens from hyperglycemic breast cancer (BC) patients to demonstrate that miR-467 mediates the effects of high blood glucose on cancer inflammation and growth. Hyperglycemic patients have a higher risk of developing breast cancer. We have identified a novel miRNA-dependent pathway activated by hyperglycemia that promotes BC angiogenesis and inflammation supporting BC growth. miR-467 is upregulated in endothelial cells (EC), macrophages, BC cells, and in BC tumors. A target of miR-467, thrombospondin-1 (TSP-1), inhibits angiogenesis and promotes resolution of inflammation. Systemic injections of a miR-467 antagonist in mouse models of hyperglycemia resulted in decreased BC growth (p < 0.001). Tumors from hyperglycemic mice had a two-fold increase in macrophage accumulation compared to normoglycemic controls (p < 0.001), and TAM infiltration was prevented by the miR-467 antagonist (p < 0.001). BC specimens from hyperglycemic patients had increased miR-467 levels, increased angiogenesis, decreased levels of TSP-1, and increased TAM infiltration in malignant breast tissue in hyperglycemic vs. normoglycemic patients (2.17-fold, p = 0.002) and even in normal breast tissue from hyperglycemic patients (2.18-fold increase, p = 0.04). In malignant BC tissue, miR-467 levels were upregulated 258-fold in hyperglycemic patients compared to normoglycemic patients (p < 0.001) and increased 56-fold in adjacent normal tissue (p = 0.008). Our results suggest that miR-467 accelerates tumor growth by inducing angiogenesis and promoting the recruitment of TAMs to drive hyperglycemia-induced cancer inflammation.
Magnetron Sputtering Thin Films as Tool to Detect Triclosan in Infant Formula Powder: Electronic Tongue Approach
Authors: Magro Cátia , Sardinha Margarida , Ribeiro Paulo A. , Raposo Maria , Sério Susana
Published: March 2021

Triclosan (TCS) is being detected in breast milk and in infants of puerperal women. The harmful effects caused by this compound on living beings are now critical and thus it is pivotal find new tools to TCS monitoring. In the present study, an electronic tongue (e-tongue) device comprising an array of sputtered thin films based on Multi-Walled Carbon Nanotubes and titanium dioxide was developed to identify TCS concentrations, from 10−15 to 10−5 M, in both water and milk-based solutions. Impedance spectroscopy was used for device signal transducing and data was analyzed by principal component analysis (PCA). The e-tongue revealed to be able to distinguish water from milk-based matrices through the two Principal Components (PC1 and PC2), which represented 67.3% of the total variance. The PC1 values of infant formula milk powder prepared with tap water (MT) or mineral water (MMW) follows a similar exponential decay curve when plotted with the logarithm of concentration. Therefore, considering the TCS concentration range between 10−15 and 10−9 M, the PC1 values are fitted by a straight line and values of −1.9 ± 0.2 and of 7.6 × 10−16 M were calculated for the sensor sensitivity and sensor resolution, respectively. Additionally, a strong correlation (R = 0.96) between MT and MMW PC1 data was found. These results have shown that the proposed device corresponds to a promisor method for the detection of TCS in milk-based solutions.
Sodium, Silver and Lithium-Ion Conducting β″-Alumina + YSZ Composites, Ionic Conductivity and Stability
Authors: Zhu Liangzhu , Virkar Anil V.
Published: March 2021

Na-β″-alumina (Na2O.~6Al2O3) is known to be an excellent sodium ion conductor in battery and sensor applications. In this study we report fabrication of Na- β″-alumina + YSZ dual phase composite to mitigate moisture and CO2 corrosion that otherwise can lead to degradation in pure Na-β″-alumina conductor. Subsequently, we heat-treated the samples in molten AgNO3 and LiNO3 to respectively form Ag-β″-alumina + YSZ and Li-β″-alumina + YSZ to investigate their potential applications in silver- and lithium-ion solid state batteries. Ion exchange fronts were captured via SEM and EDS techniques. Their ionic conductivities were measured using electrochemical impedance spectroscopy. Both ion exchange rates and ionic conductivities of these composite ionic conductors were firstly reported here and measured as a function of ion exchange time and temperature.
Strategies for High-Performance Large-Area Perovskite Solar Cells toward Commercialization
Authors: Dai Tianzhao , Cao Qiaojun , Yang Lifeng , Aldamasy Mahmoud , Li Meng , Liang Qifeng , Lu Hongliang , Dong Yiming , Yang Yingguo
Published: March 2021

Perovskite solar cells (PSCs) have received a great deal of attention in the science and technology field due to their outstanding power conversion efficiency (PCE), which increased rapidly from 3.9% to 25.5% in less than a decade, comparable to single crystal silicon solar cells. In the past ten years, much progress has been made, e.g. impressive ideas and advanced technologies have been proposed to enlarge PSC efficiency and stability. However, this outstanding progress has always been referred to as small-area (<0.1 cm2) PSCs. Little attention has been paid to the preparation processes and their micro-mechanisms for large-area (>1 cm2) PSCs. Meanwhile, scaling up is an inevitable way for large-scale application of PSCs. Therefore, we firstly summarize the current achievements for high efficiency and stability large-area perovskite solar cells, including precursor composition, deposition, growth control, interface engineering, packaging technology, etc. Then we include a brief discussion and outlook for the future development of large-area PSCs in commercialization.
The Out-of-Pocket Cost Burden of Cancer Care—A Systematic Literature Review
Authors: Iragorri Nicolas , de Oliveira Claire , Fitzgerald Natalie , Essue Beverley
Published: March 2021

Background: Out-of-pocket costs pose a substantial economic burden to cancer patients and their families. The purpose of this study was to evaluate the literature on out-of-pocket costs of cancer care. Methods: A systematic literature review was conducted to identify studies that estimated the out-of-pocket cost burden faced by cancer patients and their caregivers. The average monthly out-of-pocket costs per patient were reported/estimated and converted to 2018 USD. Costs were reported as medical and non-medical costs and were reported across countries or country income levels by cancer site, where possible, and category. The out-of-pocket burden was estimated as the average proportion of income spent as non-reimbursable costs. Results: Among all cancers, adult patients and caregivers in the U.S. spent between USD 180 and USD 2600 per month, compared to USD 15–400 in Canada, USD 4–609 in Western Europe, and USD 58–438 in Australia. Patients with breast or colorectal cancer spent around USD 200 per month, while pediatric cancer patients spent USD 800. Patients spent USD 288 per month on cancer medications in the U.S. and USD 40 in other high-income countries (HICs). The average costs for medical consultations and in-hospital care were estimated between USD 40–71 in HICs. Cancer patients and caregivers spent 42% and 16% of their annual income on out-of-pocket expenses in low- and middle-income countries and HICs, respectively. Conclusions: We found evidence that cancer is associated with high out-of-pocket costs. Healthcare systems have an opportunity to improve the coverage of medical and non-medical costs for cancer patients to help alleviate this burden and ensure equitable access to care.
Genetic Consequences of Fence Confinement in a Population of White-Tailed Deer
Authors: Latch Emily K. , Gee Kenneth L. , Webb Stephen L. , Honeycutt Rodney L. , DeYoung Randy W. , Gonzales Robert A. , Demarais Stephen , Toby Ryan
Published: March 2021

Fencing wildlife populations can aid wildlife management goals, but potential benefits may not always outweigh costs of confinement. Population isolation can erode genetic diversity and lead to the accumulation of inbreeding, reducing viability and limiting adaptive potential. We used microsatellite and mitochondrial DNA data collected from 640 white-tailed deer confined within a 1184 ha fence to quantify changes in genetic diversity and inbreeding over the first 12 years of confinement. Genetic diversity was sustained over the course of the study, remaining comparable to unconfined white-tailed deer populations. Uneroded genetic diversity suggests that genetic drift is mitigated by a low level of gene flow, which supports field observations that the fence is not completely impermeable. In year 9 of the study, we observed an unexpected influx of mtDNA diversity and drop in inbreeding as measured by FIS. A male harvest restriction imposed that year increased male survival, and more diverse mating may have contributed to the inbreeding reduction and temporary genetic diversity boost we observed. These data add to our understanding of the long-term impacts of fences on wildlife, but also highlight the importance of continued monitoring of confined populations.
Artificial Intelligence Applied to Chest X-ray for Differential Diagnosis of COVID-19 Pneumonia
Authors: Salvatore Christian , Interlenghi Matteo , Monti Caterina B. , Ippolito Davide , Capra Davide , Cozzi Andrea , Schiaffino Simone , Polidori Annalisa , Gandola Davide , Alì Marco , Castiglioni Isabella , Messa Cristina , Sardanelli Francesco
Published: March 2021

We assessed the role of artificial intelligence applied to chest X-rays (CXRs) in supporting the diagnosis of COVID-19. We trained and cross-validated a model with an ensemble of 10 convolutional neural networks with CXRs of 98 COVID-19 patients, 88 community-acquired pneumonia (CAP) patients, and 98 subjects without either COVID-19 or CAP, collected in two Italian hospitals. The system was tested on two independent cohorts, namely, 148 patients (COVID-19, CAP, or negative) collected by one of the two hospitals (independent testing I) and 820 COVID-19 patients collected by a multicenter study (independent testing II). On the training and cross-validation dataset, sensitivity, specificity, and area under the curve (AUC) were 0.91, 0.87, and 0.93 for COVID-19 versus negative subjects, 0.85, 0.82, and 0.94 for COVID-19 versus CAP. On the independent testing I, sensitivity, specificity, and AUC were 0.98, 0.88, and 0.98 for COVID-19 versus negative subjects, 0.97, 0.96, and 0.98 for COVID-19 versus CAP. On the independent testing II, the system correctly diagnosed 652 COVID-19 patients versus negative subjects (0.80 sensitivity) and correctly differentiated 674 COVID-19 versus CAP patients (0.82 sensitivity). This system appears promising for the diagnosis and differential diagnosis of COVID-19, showing its potential as a second opinion tool in conditions of the variable prevalence of different types of infectious pneumonia.
Immunity and Genetics at the Revolving Doors of Diagnostics in Primary Immunodeficiencies
Authors: Rispoli Francesco , Valencic Erica , Girardelli Martina , Pin Alessia , Tesser Alessandra , Piscianz Elisa , Boz Valentina , Faletra Flavio , Severini Giovanni Maria , Taddio Andrea , Tommasini Alberto
Published: March 2021

Primary immunodeficiencies (PIDs) are a large and growing group of disorders commonly associated with recurrent infections. However, nowadays, we know that PIDs often carry with them consequences related to organ or hematologic autoimmunity, autoinflammation, and lymphoproliferation in addition to simple susceptibility to pathogens. Alongside this conceptual development, there has been technical advancement, given by the new but already established diagnostic possibilities offered by new genetic testing (e.g., next-generation sequencing). Nevertheless, there is also the need to understand the large number of gene variants detected with these powerful methods. That means advancing beyond genetic results and resorting to the clinical phenotype and to immunological or alternative molecular tests that allow us to prove the causative role of a genetic variant of uncertain significance and/or better define the underlying pathophysiological mechanism. Furthermore, because of the rapid availability of results, laboratory immunoassays are still critical to diagnosing many PIDs, even in screening settings. Fundamental is the integration between different specialties and the development of multidisciplinary and flexible diagnostic workflows. This paper aims to tell these evolving aspects of immunodeficiencies, which are summarized in five key messages, through introducing and exemplifying five clinical cases, focusing on diseases that could benefit targeted therapy.
Integration and Disintegration of EMU Government Bond Markets
Authors: Leschinski Christian , Voges Michelle , Sibbertsen Philipp
Published: March 2021

It is commonly found that the markets for long-term government bonds of Economic and Monetary Union (EMU) countries were integrated prior to the EMU debt crisis. Contrasting this, we show, based on the interrelation between market integration and fractional cointegration, that there were periods of integration and disintegration that coincide with bull and bear market periods in the stock market. An econometric argument about the spectral behavior of long-memory time series leads to the conclusion that there is a stronger differentiation between bonds with different default risks. This implied the possibility of macroeconomic and fiscal divergence between the EMU countries before the crisis periods.
Cognitive and Functional Impairment of Hospitalized Patients over 65 Years of Age
Authors: Calero-García Mª José , Cruz Lendínez Alfonso J.
Published: March 2021

The first objective of this research is to establish and study how the different stages of cognitive impairment and the levels of dependence evolve in patients over 65 years of age, admitted to an acute care hospital, as well as the relationship between these factors and the different social and demographical variables. The results show that the level of dependence decreases suddenly at the time of admission and undergoes a slight recovery at the time of discharge. Although this recovery continues at home after discharge, patients do not get the same level of independence that they used to have before admission. In addition, significant differences in terms of age, marital status and education level were found. In general, our results show that elderly men over 80 years of age, without no education and widowers are more likely to suffer from severe cognitive impairment and be more functionally dependent when admitted to hospital.
Healthy aging: gender and lifecourse perspective cycle
Authors: Montero Mª Pilar , López-Giménez Mª Rosario , Acevedo Paula , Mora Ana I.
Published: March 2021

Objective: To identify biocultural and social factors acting at different stages of lifecourse, involved in the form of aging in women and men over 65 years. Material and Methods: The sample consists of 213 individuals; mean age was 73.9 years (std=5.8) for women and 74.8 (std=6.6) for men. Data were collected in Cultural and Leisure Centers in the Community of Madrid. Healthy aging (created from the number of diagnosed diseases, perceived health, life satisfaction, hearing and oral status) was considered as the dependent variable. The independent variables considered in this study were age, sex, educational level, sitting height, spam, age at first maternity and the total number of children. Linear multiple regression models were used for statistical analysis. Results: Healthy aging was negatively associated with age and positively with the sitting height in men. In women, healthy aging was positively associated with years of education, when age at first motherhood is included in the model, this in the only variable remaining with a significant effect. Conclusions: There are several factors acting across the life of men and women and that affect differently the way women and men get old.
Leisure, recreation and quality of life for active aging, University of Burgos case
Authors: Gañán Ángel , Villafruela Itxaso
Published: March 2021

With this research we try to find the relationship between the entertainment, leisure and perceived quality of life by students attending our education program for older people achieving aging asset quality. We are at present a major challenge to the achievement of welfare all inclusive society and to all groups within it. As we can confirm in the report published in 2008 by IMSERSO in 2010 17.2% of total the population was at an age of 65 years. The growth rate of the population is 1.26% higher than the average annual population growth. Overall, in Spain we can see this change in the demographic trend, it also assures us as the median age of the Spanish settlement established in the year 2000 to 38.8 years. The projected median age in 2050 will stand at 49.5 years positioning ourselves for that year above the European Middle Ages. with this describe how research in our Educational Program for People Major contributing to active aging cataloging data on Leisure, the Leisure and the Quality of Life. The work will also compare the data obtained by sex and age to compare them with other statistics official published so far at both state and international level.
Effect size and meta-analysis in Spanish professional psychologists
Authors: Badenes-Ribera Laura , Frías-Navarro Dolores , Bonilla-Campos Amparo
Published: March 2021

The Evidence-Based Practice approach is based on the use of scientific research in decision-making in an effort to produce the best possible services in clinical practice. The knowledge level about effect size statistics and meta-analysis studies may affect the decision soft professionals and jeopardize the quality of psychological interventions. This paper presents the result so fan on-line survey on the degree of knowledge of these topics among Spanish practitioner psychologists. The sample consisted of 77 participants (68.8% women and 31.2% men), with a mean age of 41.44 years (SD=9.42), with age range of 25-64 years. The results suggest that most of the psychologists survey eddid not have adequate knowledge about effect size index, meta-analysis studies, or methodological quality checklists. It is therefore necessary to improve the statistical education of practitioner psychologists, which might also contribute to their provement of professional practice.
A Hybrid Supervised Machine Learning Classifier System for Breast Cancer Prognosis Using Feature Selection and Data Imbalance Handling Approaches
Authors: Solanki Yogendra Singh , Chakrabarti Prasun , Jasinski Michal , Leonowicz Zbigniew , Bolshev Vadim , Vinogradov Alexander , Jasinska Elzbieta , Gono Radomir , Nami Mohammad
Published: March 2021

Nowadays, breast cancer is the most frequent cancer among women. Early detection is a critical issue that can be effectively achieved by machine learning (ML) techniques. Thus in this article, the methods to improve the accuracy of ML classification models for the prognosis of breast cancer are investigated. Wrapper-based feature selection approach along with nature-inspired algorithms such as Particle Swarm Optimization, Genetic Search, and Greedy Stepwise has been used to identify the important features. On these selected features popular machine learning classifiers Support Vector Machine, J48 (C4.5 Decision Tree Algorithm), Multilayer-Perceptron (a feed-forward ANN) were used in the system. The methodology of the proposed system is structured into five stages which include (1) Data Pre-processing; (2) Data imbalance handling; (3) Feature Selection; (4) Machine Learning Classifiers; (5) classifier’s performance evaluation. The dataset under this research experimentation is referred from the UCI Machine Learning Repository, named Breast Cancer Wisconsin (Diagnostic) Data Set. This article indicated that the J48 decision tree classifier is the appropriate machine learning-based classifier for optimum breast cancer prognosis. Support Vector Machine with Particle Swarm Optimization algorithm for feature selection achieves the accuracy of 98.24%, MCC = 0.961, Sensitivity = 99.11%, Specificity = 96.54%, and Kappa statistics of 0.9606. It is also observed that the J48 Decision Tree classifier with the Genetic Search algorithm for feature selection achieves the accuracy of 98.83%, MCC = 0.974, Sensitivity = 98.95%, Specificity = 98.58%, and Kappa statistics of 0.9735. Furthermore, Multilayer Perceptron ANN classifier with Genetic Search algorithm for feature selection achieves the accuracy of 98.59%, MCC = 0.968, Sensitivity = 98.6%, Specificity = 98.57%, and Kappa statistics of 0.9682.
Impact of Management Tools Supporting Industry 4.0 on the Importance of CSR during COVID-19. Generation Z
Authors: Cyfert Szymon , Glabiszewski Waldemar , Zastempowski Maciej
Published: March 2021

Taking into account the impact of the COVID-19 and adopting the assessment optics of students from Generation Z currently entering the labor market, we have made the aim of this article to provide better insight into the relationship between Industry 4.0 and corporate social responsibility. The survey was conducted in the form of an online survey in two leading universities in Poland in the field of economic education. 646 students took part in the survey. The data were analyzed using logit regression models. The results of the study suggest that the increase in the use of management solutions supporting Industry 4.0 in the wake of the COVID-19 crisis will increase the importance of the economic, social, and environmental dimensions of corporate social responsibility. Pointing to the forecasted increase importance of corporate social responsibility, we suggest linking management solutions supporting Industry 4.0 with corporate social responsibility. However, we also draw attention to the impact of individual management solutions supporting Industry 4.0 on specific Corporate Social Responsibility (CSR) dimensions.
Entropy Rates and Efficiency of Convecting-Radiating Fins
Authors: Giorgi Claudio , Zullo Federico
Published: March 2021

We present a novel indicator for the effectiveness of longitudinal, convecting-radiating fins to dissipate heat. Starting from an analysis of the properties of the entropy rate of the steady state, we show how it is possible to assess the efficiency of such devices by looking at the amount of entropy produced in the heat transfer process. Our study concerns both purely convective fins and convection-radiant fins and takes advantage of explicit expressions for the distribution of heat along the fin. It is shown that, in a suitable limit, the standard definition of efficiency and the entropic definition coincide. The role of the fluid temperature is explicit in the new definition and in the purely convective case. An application to an aluminium fin is given. Analytical and numerical results are discussed.
Wet Drilled Cuttings Bed Rheology
Authors: Pedrosa Camilo , Saasen Arild , Lund Bjørnar , Ytrehus Jan David
Published: March 2021

The cuttings transport efficiency of various drilling fluids has been studied in several approaches. This is an important aspect, since hole cleaning is often a bottleneck in well construction. The studies so far have targeted the drilling fluid cuttings’ transport capability through experiments, simulations or field data. Observed differences in the efficiency due to changes in the drilling fluid properties and compositions have been reported but not always fully understood. In this study, the cuttings bed, wetted with a single drilling fluid, was evaluated. The experiments were performed with parallel plates in an Anton Paar Physica 301 rheometer. The results showed systematic differences in the internal friction behaviors between tests of beds with oil-based and beds with water-based fluids. The observations indicated that cutting beds wetted with a polymeric water-based fluid released clusters of particles when external forces overcame the bonding forces and the beds started to break up. Similarly, it was observed that an oil-based fluid wetted bed allowed particles to break free as single particles. These findings may explain the observed differences in previous cutting transport studies.
Investigations of the Dynamic Travel Time Information Impact on Drivers’ Route Choice in an Urban Area—A Case Study Based on the City of Bialystok
Authors: Ziółkowski Robert , Dziejma Zbigniew
Published: March 2021

Increasing traffic volumes in cities leads to common traffic congestions building up, especially during peak hours. To protect city dwellers from excessive fuel exhaust and traffic noise and to prevent drivers from time loss due to overloaded routes, it is important to inform them about real-time traffic conditions and possible delays in advance. Effectively influencing drivers’ decisions to divert from an original route choice in case of traffic hinderance is essential, and application of dynamic travel information in the form of variable message signs (VMSs) is believed to be effective in these terms. The paper examines drivers’ willingness to divert from an initial route choice due to the information provided on VMS boards. Their behavior was analyzed in terms of their response to everyday and artificially elongated travel times displayed on the VMSs. Maximum simulated elongation reached 200% and 300% of the initial state, depending on the characteristics of the pre-peak conditions. To assess the effectiveness of VMSs, the changes in traffic intensities were statistically analyzed. In general, apart from few significant differences, the results revealed drivers’ ignorance of the travel time information provided on the VMS, regardless of the extension of the original times.