bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Psychological Reactions and Psychological Aids for Medical Staff During the COVID-19 Outbreak in China
Authors: Su Qinji , Ma Xiaoyun , Liu Shun , Liu Shaogang , Goodman Bernard A. , Yu Miaoyu , Guo Wenbin
Published: April 2021

Background: The outbreak of the novel coronavirus disease COVID-19 caused panic and psychological stress throughout the World. We investigated the extent of adverse psychological reactions in two medical staff groups in China, and explored the importance of online psychological assistance for them.

Methods: A cross-sectional online survey including Hospital Anxiety and Depression Scale (HADS) and Insomnia Severity Index (ISI) was utilized to assess anxiety, depression, and insomnia. Propensity score matching (PSM) was applied to match sex and age between the two groups. Differences in the prevalence of adverse psychological reactions between the two groups were compared by a Chi-square test. A multivariate logistic regression analysis was utilized to search for associated adverse psychological reaction factors of two groups.

Results: A total of 2,920 medical staff took part in the survey, including 470 frontline and 2,450 non-frontline medical staff. The risk of the frontline group experiencing anxiety, depression, insomnia-early, insomnia-middle, and insomnia-late were 1.16, 1.28, 1.26, 1.22, 1.28 times those of the non-frontline group after PSM. For frontline medical staff, the spinsterhood state (OR = 1.23, 95% CI: 1.00–1.51; P = 0.05) was a risk factor for anxiety. Bachelor or college degree (OR = 2.23, 95% CI: 1.24–4.02, P = 0.01) and a contact history with COVID-19 patients (OR = 1.62, 95% CI: 1.10–2.40; P = 0.02) were risk factors for insomnia. For non-frontline medical staff, being a woman (OR = 1.49, 95% CI: 1.08–2.06, P = 0.01) was a risk factor for anxiety, whilst being in a middle age group was a protective factor for anxiety (OR = 0.70, 95% CI: 0.50–0.99, P = 0.04) and depression (OR = 0.65, 95% CI: 0.45–0.93, P = 0.02). Being a woman (OR = 1.47, 95% CI: 1.14–1.89, P = 0.003) and working in a COVID-19 unit (OR = 1.31, 95% CI: 1.11–1.54, P = 0.001) were risk factors for insomnia, whilst the spinsterhood state (OR = 0.80, 95% CI: 0.67–0.95; P = 0.01) was a protective factor for insomnia. Online forms of psychological aid were all popular with medical staff.

Conclusions: The prevalence of anxiety, depression, and insomnia in frontline medical staff was significantly higher than in the non-frontline group. Appropriate intervention methods should be adopted according to the different influencing factors of the two groups. Online psychological aid was the preferred mechanism for relieving psychological problems.
Negative Appraisals of the COVID-19 Social Impact Associated With the Improvement of Depression and Anxiety in Patients After COVID-19 Recovery
Authors: Chen Wentao , Ju Yumeng , Liu Bangshan , Huang Mei , Yang Aiping , Zhou Yun , Wang Mi , Liao Mei , Shu Kongliang , Liu Jiyang , Zhang Yan
Published: April 2021

Objective: Little is known about the factors affecting the recovery of mental health in COVID-19 patients. The purpose of this study is to look into the change of psychological distress and to explore the role of negative appraisals in the improvement of psychological distress in COVID-19 patients after they recovered from the infection.

Methods: We conducted a longitudinal survey on patients with COVID-19 infection in Changsha. The 9-item Patient Health scale, the 7-item Generalized Anxiety Disorder scale, and a newly developed measure, the COVID-19 Impact Scale (CIS) were applied to assess patients' depression, anxiety, and negative appraisal toward COVID-19 infection during their hospitalization and 1 month post-discharge.

Results: Seventy-two patients were included in the analysis. A significant decrease in anxiety and depression levels was observed after patients were discharged from hospital. Two meaningful factors of the CIS were extracted based on factor analysis, namely “health impact,” and “social impact.” The change of social impact explained the 12.7 and 10.5% variance in the depression and anxiety symptom improvement, respectively.

Conclusions: Change in negative appraisals, especially the appraisals related to COVID-19 social impact may play a vital role in the relief of psychological distress of infected patients. Therefore, a cognitive and social care perspective might be considered when promoting the mental health recovery and readjustment to society among COVID-19 patients.
Autism-Associated Variant in the SLC6A3 Gene Alters the Oral Microbiome and Metabolism in a Murine Model
Authors: DiCarlo Gabriella E. , Mabry Samuel J. , Cao Xixi , McMillan Clara , Woynaroski Tiffany G. , Harrison Fiona E. , Reddy India A. , Matthies Heinrich J. G. , Flynn Charles R. , Wallace Mark T. , Wu Hui , Galli Aurelio
Published: April 2021

Background: Altered dopamine (DA) signaling has been associated with autism spectrum disorder (ASD), a neurodevelopmental condition estimated to impact 1 in 54 children in the United States. There is growing evidence for alterations in both gastrointestinal function and oral microbiome composition in ASD. Recent work suggests that rare variants of the SLC6A3 gene encoding the DA transporter (DAT) identified in individuals with ASD result in structural and functional changes to the DAT. One such recently identified de novo mutation is a threonine to methionine substitution at position 356 of the DAT (DAT T356M). The DAT T356M variant is associated with ASD-like phenotypes in mice homozygous for the mutation (DAT T356M+/+), including social deficits, hyperactivity, and impaired DA signaling. Here, we determine the impact of this altered DA signaling as it relates to altered oral microbiota, and metabolic and gastrointestinal dysfunction.

Methods: In the DAT T356M+/+ mouse, we determine the oral microbiota composition, metabolic function, and gastrointestinal (GI) function. We examined oral microbiota by 16S RNA sequencing. We measured metabolic function by examining glucose tolerance and we probed gastrointestinal parameters by measuring fecal dimensions and weight.

Results: In the DAT T356M+/+ mouse, we evaluate how altered DA signaling relates to metabolic dysfunction and altered oral microbiota. We demonstrate that male DAT T356M+/+ mice weigh less (Wild type (WT) = 26.48 ± 0.6405 g, DAT T356M+/+ = 24.14 ± 0.4083 g) and have decreased body fat (WT = 14.89 ± 0.6206%, DAT T356M+/+ = 12.72 ± 0.4160%). These mice display improved glucose handling (WT = 32.60 ± 0.3298 kcal/g, DAT T356M+/+ = 36.97 ± 0.4910 kcal/g), and an altered oral microbiota. We found a significant decrease in Fusobacterium abundance. The abundance of Fusobacterium was associated with improved glucose handling and decreased body fat.

Conclusions: Our findings provide new insights into how DAT dysfunction may alter gastrointestinal function, composition of the oral microbiota, and metabolism. Our data suggest that impaired DA signaling in ASD is associated with a number of metabolic and gastrointestinal changes which are common in individuals with ASD.
Genomic Analysis and Lineage Identification of SARS-CoV-2 Strains in Migrants Accessing Europe Through the Libyan Route
Authors: Tramuto Fabio , Reale Stefano , Lo Presti Alessandra , Vitale Francesco , Pulvirenti Claudio , Rezza Giovanni , Vitale Fabrizio , Purpari Giuseppa , Maida Carmelo Massimo , Zichichi Salvatore , Scibetta Silvia , Mazzucco Walter , Stefanelli Paola
Published: April 2021

Many African countries, representing the origin of the majority of refugees, asylum-seekers, and other migrants, toward regions bordering on the Mediterranean area, are experiencing sustained local transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sicily is one of the main entry gates of migrants crossing into Europe. We conducted a pilot study, based on the full-genome sequencing of SARS-CoV-2 strains isolated from migrants coming to Sicily by crossing the Mediterranean Sea, with the aim to investigate the viral genome polymorphism and to describe their genetic variations and the phylogenetic relationships. On June 21, a nongovernmental organization vessel rescued 210 migrants crossing the Mediterranean Sea from Libya to Sicily. Of them, 13.4% tested positive for SARS-CoV-2. Eighteen whole genome sequences were obtained to explore viral genetic variability. All but one of the sequences clustered with other viral African strains within the lineage A, whereas only one intermixed among B.1 lineage genomes. Our findings documented that most of the investigated migrants acquired SARS-CoV-2 infection before landing in Sicily. However, SARS-CoV-2 transmission during travel or in overcrowded Libyan immigrant camps and/or illegal transport boats could not be ruled out. SARS-CoV-2 molecular surveillance on migrants arriving in Europe through the Sicilian gate may improve the knowledge of global SARS-CoV-2 transmission dynamic also in light of the emergence of new variants.
Research and Management of Rare Diseases in the COVID-19 Pandemic Era: Challenges and Countermeasures
Authors: Chowdhury Sanjana Fatema , Sium Syed Muktadir Al , Anwar Saeed
Published: April 2021

The ongoing coronavirus disease 2019 (COVID-19) pandemic has disrupted every aspect of our life. The need to provide high-level care for an enormous number of patients with COVID-19 infection during this pandemic has impacted resourcing for and restricted the routine care of all non-COVID-19 conditions. Since the beginning of the pandemic, the people living with rare disorders, who represent a marginalized group of the population even in a normal world, have not received enough attention that they deserve. Due to the pandemic situation, they have experienced (and experiencing) an extreme inadequacy of regular clinical services, counseling, and therapies they need, which have made their life more vulnerable and feel more marginalized. Besides, the clinicians, researchers, and scientists working on rare genetic diseases face extra challenges due to the pandemic. Many ongoing research projects and clinical trials for rare and genetic diseases were stalled to avoid patients' and research staff's transmission to COVID-19. Still, with all the odds, telehealth and virtual consultations for rare disease patients have shown hope. The clinical, organizational, and economic challenges faced by institutions, patients, their families, and the caregivers during the pandemic indicate the importance of ensuring continuity of care in managing rare diseases, including adequate diagnostics and priority management strategies for emergencies. In this review, we endeavored to shed light on the issues the rare disease community faces during the pandemic and the adaptations that could help the rare disease community to better sustain in the coming days.
Fatigue Damage–Resistant Physical Hydrogel Adhesion
Authors: Li Qi , Wang Luochang , Liu Qihan , Hong Wei , Yang Canhui
Published: April 2021

Strong adhesion between hydrogels and various engineering surfaces has been achieved; yet, achieving fatigue-resistant hydrogel adhesion remains challenging. Here, we examine the fatigue of a specific type of hydrogel adhesion enabled by hydrogen bonds and wrinkling and show that the physical interactions–based hydrogel adhesion can resist fatigue damage. We synthesize polyacrylamide hydrogel as the adherend and poly(acrylic acid-co-acrylamide) hydrogel as the adhesive. The adherend and the adhesive interact via hydrogen bonds. We further introduce wrinkles at the interface by biaxially prestretching and then releasing the adherends and perform butt-joint tests to probe the adhesion performance. Experimental results reveal that the samples with a wrinkled interface resist fatigue damage, while the samples with a flat interface fail in ~9,000 cycles at stress levels of 70 and 63% peak stresses in static failure. The endurance limit of the wrinkled-interface samples is comparable to the peak stress of the flat-interface samples. Moreover, we find that the nearly perfectly elastic polyacrylamide hydrogel also suffers fatigue damage, which limits the fatigue life of the wrinkled-interface samples. When cohesive failure ensues, the evolutions of the elastic modulus of wrinkled-interface samples and hydrogel bulk, both in satisfactory agreements with the predictions of damage accumulation theory, are alike. We observe similar behaviors in different material systems with polyacrylamide hydrogels with different water contents. This work proves that physical interactions can be engaged in engineering fatigue-resistant adhesion between soft materials such as hydrogels.
When It Rains, It Pours: Integrating Citizen Science Methods to Understand Resilience of Urban Green Spaces
Authors: Pudifoot Bethany , Cárdenas Macarena L. , Buytaert Wouter , Paul Jonathan D. , Narraway Claire L. , Loiselle Steven
Published: April 2021

Urban green spaces are often promoted as nature-based solutions, thus helping to mitigate the negative effects of climate change. Estimating the potential environmental benefits provided by urban green space is difficult because of inconsistencies in management practices and their heterogeneous nature. Collecting data across such a spectrum of contexts at a large scale is costly and time consuming. In this study, we explore a novel integrated method for citizen scientists to assess the flood mitigation potential of urban green spaces. In three European cities, citizen scientists measured infiltration rate and associated soil characteristics in managed and unmanaged urban green spaces. The results show that simple citizen science-based measurements can indicate the infiltration potential (i.e., high vs. low) of soil at these sites. Infiltration rate was best predicted by measurements of soil compaction, soil color, air temperature, and level of insolation (i.e., high vs. low). These simple, fast methods can be repeated over time and space by citizen scientists to provide robust estimates of soil characteristics and the infiltration potential of soils that exist in similar temperate urban areas. A classification flow diagram was constructed and validated that allows citizen scientists to carry out such tests over a wider geographical region and at a higher frequency than would be available to research scientists alone. Most importantly, it allows citizens to take actions to improve infiltration in their local green space and support local flood resilience.
Caloric Restriction in Group-Housed Mice: Littermate and Sex Influence on Behavioral and Hormonal Data
Authors: Perea Cristina , Vázquez-Ágredos Ana , Ruiz-Leyva Leandro , Morón Ignacio , Zúñiga Jesús Martín , Cendán Cruz Miguel
Published: April 2021

Much of the research done on aging, oxidative stress, anxiety, and cognitive and social behavior in rodents has focused on caloric restriction (CR). This often involves several days of single housing, which can cause numerous logistical problems, as well as cognitive and social dysfunctions. Previous results in our laboratory showed the viability of long-term CR in grouped rats. Our research has studied the possibility of CR in grouped female and male littermates and unrelated CB6F1/J (C57BL/6J × BALBc/J hybrid strain) mice, measuring: (i) possible differences in body mass proportions between mice in ad libitum and CR conditions (at 70% of ad libitum), (ii) aggressive behavior, using the number of pushes and chasing behavior time as an indicator and social behavior using the time under the feeder as indicator, and (iii) difference in serum adrenocorticotropic hormone (ACTH) concentrations (stress biomarker), under ad libitum and CR conditions. Results showed the impossibility of implementing CR in unrelated male mice. In all other groups, CR was possible, with a less aggressive behavior (measured only with the number of pushes) observed in the unrelated female mice under CR conditions. In that sense, the ACTH levels measured on the last day of CR showed no difference in stress levels. These results indicate that implementantion of long-term CR in mice can be optimized technically and also related to their well-being by grouping animals, in particular, related mice.
Modulatory Effects of Echinococcus multilocularis emu-let-7-5p on the Immunological Functions of RAW264.7 Macrophages
Authors: Jin Xiaoliang , Li Yating , Yang Xing , Zheng Yadong
Published: April 2021

Echinococcus multilocularis is a zoonotic tapeworm with great medical significance. In E. multilocularis-infected mice, parasite-derived let-7-5p (emu-let-7-5p) is present in the sera, but its role remains unclear. Using qPCR, ELISA and flow cytometry, the immunomodulatory effects of emu-let-7-5p were in vitro investigated using RAW264.7 macrophages. Compared with the control, emu-let-7-5p significantly downregulated IL-1α (p < 0.05), but anti-inflammatory cytokine genes remained to be stably expressed in the treated macrophages. Moreover, significantly decreased expression of ripk1 and nf-kB, key components in the LPS/TLR4 signaling pathway, was also observed in the emu-let-7-5p-transfected cells (p < 0.05). Furthermore, CD40 was upregulated in these transfected cells (p < 0.05), while CD86, CD54 and CD80 remained unchanged compared that in the control. These results demonstrate a property of emu-let-7-5p in regulation of immune functions of macrophages, making it be possibly involved in the pathogen-host interplay during E. multilocularis infection.
The Efficiency of Spa Rehabilitation in Chronic Ischemic Stroke Patients—Preliminary Reports
Authors: Pniak Bogumiła , Leszczak Justyna , Kurczab Jadwiga , Krzemińska Aleksandra , Pięta Joanna , Plis Agnieszka , Czenczek-Lewandowska Ewelina , Guzik Agnieszka
Published: April 2021

Background: Rehabilitation-oriented therapy after a stroke must continue in various forms as a life-long effort. Aim: The study investigated the impact of spa rehabilitation on the quality of life and functional efficiency in patients after an ischemic stroke at a chronic stage of recovery. Methods: The assessment was carried out in a spa resort in southeastern Poland. It involved 32 patients with strokes who participated in a three-week rehabilitation program. Three examinations were performed: upon admission, on the day of discharge and at a two-month follow-up. The quality of life and functional efficiency were assessed with the WHOQOL-BREF and Barthel Index. Results: The quality of life was significantly higher in Exam II compared with Exam I (p < 0.001), and improvement was retained at the follow-up. The Barthel scores were higher in Exam II compared with Exam I (79.84 vs. 68.59), while the differences between the scores in Exams II and III were small (p = 0.039). Conclusions: Three-week spa rehabilitation seems to favorably affect the functional efficiency and quality of life after a stroke. The effects appear to be long-term. The gender, age and time from stroke onset do not seem to impact short-term effects. However, long-term effects are related to the time from stroke onset.
Potential Therapeutic Significance of Laminin in Head and Neck Squamous Carcinomas
Authors: Meireles Da Costa Nathalia , Mendes Fábio A. , Pontes Bruno , Nasciutti Luiz Eurico , Ribeiro Pinto Luis Felipe , Palumbo Júnior Antonio
Published: April 2021

Head and neck squamous cell carcinomas (HNSCC) are among the most common and lethal tumors worldwide, occurring mostly in oral cavity, pharynx, and larynx tissues. The squamous epithelia homeostasis is supported by the extracellular matrix (ECM), and alterations in this compartment are crucial for cancer development and progression. Laminin is a fundamental component of ECM, where it represents one of the main components of basement membrane (BM), and data supporting its contribution to HNSCC genesis and progression has been vastly explored in oral cavity squamous cell carcinoma. Laminin subtypes 111 (LN-111) and 332 (LN-332) are the main isoforms associated with malignant transformation, contributing to proliferation, adhesion, migration, invasion, and metastasis, due to its involvement in the regulation of several pathways associated with HNSCC carcinogenesis, including the activation of the EGFR/MAPK signaling pathway. Therefore, it draws attention to the possibility that laminin may represent a convergence point in HNSCC natural history, and an attractive potential therapeutic target for these tumors.
Cancer Nanopharmaceuticals: Physicochemical Characterization and In Vitro/In Vivo Applications
Authors: Zielińska Aleksandra , Szalata Marlena , Gorczyński Adam , Karczewski Jacek , Eder Piotr , Severino Patrícia , Cabeda José M. , Souto Eliana B. , Słomski Ryszard
Published: April 2021

Physicochemical, pharmacokinetic, and biopharmaceutical characterization tools play a key role in the assessment of nanopharmaceuticals’ potential imaging analysis and for site-specific delivery of anti-cancers to neoplastic cells/tissues. If diagnostic tools and therapeutic approaches are combined in one single nanoparticle, a new platform called nanotheragnostics is generated. Several analytical technologies allow us to characterize nanopharmaceuticals and nanoparticles and their properties so that they can be properly used in cancer therapy. This paper describes the role of multifunctional nanoparticles in cancer diagnosis and treatment, describing how nanotheragnostics can be useful in modern chemotherapy, and finally, the challenges associated with the commercialization of nanoparticles for cancer therapy.
Histopathologic, Genetic and Molecular Characterization of Endometrial Cancer Racial Disparity
Authors: Javadian Pouya , Washington Christina , Mukasa Shylet , Benbrook Doris Mangiaracina
Published: April 2021

In contrast to the decline in incidence and mortality of most other cancers, these rates are rising for endometrial cancer. Black women with endometrial cancer have earlier diagnosis, more aggressive histology, advanced stage and worse outcomes compared with their White counterparts. Socioeconomic status, a higher incidence of aggressive histology, and comorbid conditions are known factors leading to racial disparity in patients with endometrial cancer; nevertheless, they do not account for the entire racial disparity; which emphasizes the roles of molecular, histopathological and genetic factors. We performed a comprehensive review of all published scientific literature up to January 2021 reporting histopathologic, genetic and molecular factors associated with racial disparities in patients with endometrial cancer. The interactions and pathways of molecules reported to have significant differential expression in endometrial cancers from Black and White patients were identified with Ingenuity Pathway Analysis. The majority of studies compared Black and White patients; however, limited data are available for other racial and ethnic groups. Reported differences that could account for the worse survival of Black endometrial cancer patients include more aggressive histopathologies and molecular alterations, including upregulation of molecules driving cell cycle progression, and p53 and HER2/NEU signaling. Several of these molecules are targeted by existing pharmaceuticals. These findings encourage further study and the development of race-specific treatment strategies.
Immunotherapy Combined with Metronomic Dosing: An Effective Approach for the Treatment of NSCLC
Authors: Skavatsou Eleni , Semitekolou Maria , Morianos Ioannis , Karampelas Theodoros , Lougiakis Nikolaos , Xanthou Georgina , Tamvakopoulos Constantin
Published: April 2021

Pioneering studies on tumor and immune cell interactions have highlighted immune checkpoint inhibitors (ICIs) as revolutionizing interventions for the management of NSCLC, typically combined with traditional MTD chemotherapies, which usually lead to toxicities and resistance to treatment. Alternatively, MTR chemotherapy is based on the daily low dose administration of chemotherapeutics, preventing tumor growth indirectly by targeting the tumor microenvironment. The effects of MTR administration of an oral prodrug of gemcitabine (OralGem), alone or with anti-PD1, were evaluated. Relevant in vitro and in vivo models were developed to investigate the efficacy of MTR alone or with immunotherapy and the potential toxicities associated with each dosing scheme. MTR OralGem restricted tumor angiogenesis by regulating thrombospondin-1 (TSP-1) and vascular endothelial growth factor A (VEGFA) expression. MTR OralGem enhanced antitumor immunity by increasing T effector responses and cytokine release, concomitant with dampening regulatory T cell populations. Promising pharmacokinetic properties afforded minimized blood and thymus toxicity and favorable bioavailability upon MTR administration compared to MTD. The combination of MTR OralGem with immunotherapy was shown to be highly efficacious and tolerable, illuminating it as a strong candidate therapeutic scheme for the treatment of NSCLC.
Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group
Authors: Caravatta Luciana , Mantello Giovanna , Valvo Francesca , Franco Pierfrancesco , Gasparini Lucrezia , Rosa Consuelo , Slim Najla , Manfrida Stefania , De Felice Francesca , Gerardi Marianna A. , Vagge Stefano , Krengli Marco , Palazzari Elisa , Osti Maria Falchetto , Gonnelli Alessandra , Catalano Gianpiero , Pittoni Patrizia , Ivaldi Giovani Battista , Galardi Alessandra , Lupattelli Marco , Rosetto Maria Elena , Niespolo Rita Marina , Guido Alessandra , Durante Oreste , Macchia Gabriella , Munoz Fernando , El khouzai Badr , Lucido Maria Rosaria , Porreca Annamaria , Di Nicola Marta , Gambacorta Maria Antonietta , Donato Vittorio , Genovesi Domenico
Published: April 2021

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.
Circular RNA in Chemonaive Lymph Node Negative Colon Cancer Patients
Authors: van den Berg Inge , Smid Marcel , Coebergh van den Braak Robert R. J. , van Deurzen Carolien H. M. , de Weerd Vanja , Foekens John A. , IJzermans Jan N. M. , Martens John W. M. , Wilting Saskia M.
Published: April 2021

Circular RNAs (circRNAs) appear important in tumor progression of colon cancer (CC). We identified an extensive catalog of circRNAs in 181 chemonaive stage I/II colon tumors, who underwent curative surgery between 2007 and 2014. We identified circRNAs from RNAseq data, investigated common biology related to circRNA expression, and studied the association between circRNAs and relapse status, tumor stage, consensus molecular subtypes (CMS), tumor localization and microsatellite instability (MSI). We identified 2606 unique circRNAs. 277 circRNAs (derived from 260 genes) were repeatedly occurring in at least 20 patients of which 153 showed a poor or even negative (R < 0.3) correlation with the expression level of their linear gene. The circular junctions for circSATB2, circFGD6, circKMT2C and circPLEKHM3 were validated by Sanger sequencing. Multiple correspondence analysis showed that circRNAs were often co-expressed and that high diversity in circRNAs was associated with favorable disease-free survival (DFS), which was confirmed by Cox regression analysis (Hazard Ratio (HR) 0.60, 95% CI 0.38–0.97, p = 0.036). Considering individual circRNAs, absence of circMGA was significantly associated with relapse, whereas circSATB2, circNAB1, and circCEP192 were associated with both MSI and CMS. This study represents a showcase of the potential clinical utility of circRNAs for prognostic stratification in patients with stage I–II colon cancer and demonstrated that high diversity in circRNAs is associated with favorable DFS.
Hypoxia-Driven HIF-1α Activation Reprograms Pre-Activated NK Cells towards Highly Potent Effector Phenotypes via ERK/STAT3 Pathways
Authors: Lim Seon Ah , Moon Yunwon , Shin Min Hwa , Kim Tae-Jin , Chae Sehyun , Yee Cassian , Hwang Daehee , Park Hyunsung , Lee Kyung-Mi
Published: April 2021

NK cells are the predominant innate lymphocyte subsets specialized to kill malignant tumor cells. In patients with advanced cancer, hypoxic stress shapes NK cells toward tumor-resistant and immunosuppressive phenotypes, hence a strategy to restore NK function is critical for successful tumor immunotherapy. Here, we present evidence that pre-activation and subsequent HIF-1α-dependent metabolic shift of NK cells from oxidative phosphorylation into glycolysis are keys to overcome hypoxia-mediated impairment in NK cell survival, proliferation, and tumor cytotoxicity. Specifically, exposing NK cells to 7–9 days of normoxic culture followed by a pO2 of 1.5% hypoxia led to a highly potent effector phenotype via HIF-1α stabilization and upregulation of its target genes, BNIP3, PDK1, VEGF, PKM2, and LDHA. RNA sequencing and network analyses revealed that concomitant reduction of p21/p53 apoptotic pathways along with upregulation of cell cycle-promoting genes, CCNE1, CDC6, CDC20, and downregulation of cell cycle-arrest genes, CDKN1A, GADD45A, and MDM2 were accountable for superior expansion of NK cells via ERK/STAT3 activation. Furthermore, HIF-1α-dependent upregulation of the NKp44 receptor in hypoxia-exposed NK cells resulted in increased killing against K562, CEM, and A375 tumor targets both in-vitro and in-vivo tumor clearance assays. Therefore, hypoxic exposure on pre-activated proliferating NK cells triggered HIF-1α-dependent pathways to initiate coordinated regulation of cell cycle, apoptosis, and cytotoxicity at the global gene transcription level. Our results uncover a previously unidentified role of HIF-1α-mediated metabolic reprogramming that can reverse impaired NK effector phenotypes to generate requisite numbers of functionally robust NK cells for adoptive cellular therapy for clinical evaluation.
Automated Non-Coplanar VMAT for Dose Escalation in Recurrent Head and Neck Cancer Patients
Authors: Woods Kaley , Chin Robert K. , Cook Kiri A. , Sheng Ke , Kishan Amar U. , Hegde John V. , Tenn Stephen , Steinberg Michael L. , Cao Minsong
Published: April 2021

This study evaluates the potential for tumor dose escalation in recurrent head and neck cancer (rHNC) patients with automated non-coplanar volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) planning (HyperArc). Twenty rHNC patients are planned with conventional VMAT SBRT to 40 Gy while minimizing organ-at-risk (OAR) doses. They are then re-planned with the HyperArc technique to match these minimal OAR doses while escalating the target dose as high as possible. Then, we compare the dosimetry, tumor control probability (TCP), and normal tissue complication probability (NTCP) for the two plan types. Our results show that the HyperArc technique significantly increases the mean planning target volume (PTV) and gross tumor volume (GTV) doses by 10.8 ± 4.4 Gy (25%) and 11.5 ± 5.1 Gy (26%) on average, respectively. There are no clinically significant differences in OAR doses, with maximum dose differences of <2 Gy on average. The average TCP is 23% (± 21%) higher for HyperArc than conventional plans, with no significant differences in NTCP for the brainstem, cord, mandible, or larynx. HyperArc can achieve significant tumor dose escalation while maintaining minimal OAR doses in the head and neck—potentially enabling improved local control for rHNC SBRT patients without increased risk of treatment-related toxicities.
Alternative Vascularization Mechanisms in Tumor Resistance to Therapy
Authors: Belotti Dorina , Pinessi Denise , Taraboletti Giulia
Published: April 2021

Blood vessels in tumors are formed through a variety of different mechanisms, each generating vessels with peculiar structural, molecular, and functional properties. This heterogeneity has a major impact on tumor response or resistance to antineoplastic therapies and is now emerging as a promising target for strategies to prevent drug resistance and improve the distribution and efficacy of antineoplastic treatments. This review presents evidence of how different mechanisms of tumor vessel formation (vasculogenesis, glomeruloid proliferation, intussusceptive angiogenesis, vasculogenic mimicry, and vessel co-option) affect tumor responses to antiangiogenic and antineoplastic therapies, but also how therapies can promote alternative mechanisms of vessel formation, contributing to tumor recurrence, malignant progression, and acquired drug resistance. We discuss the possibility of tailoring treatment strategies to overcome vasculature-mediated drug resistance or to improve drug distribution and efficacy.
Progress on Research Regarding Ecology and Biodiversity of Coastal Fisheries and Nektonic Species and Their Habitats within Coastal Landscapes
Authors: Peterson Mark S. , Andres Michael J.
Published: April 2021

This paper aims to highlight the new research and significant advances in our understanding of links between coastal habitat quality/quantity/diversity and the diversity of fisheries species and other mobile aquatic species (hereafter nekton) that use them within coastal landscapes. This topic is quite diverse owing to the myriad of habitat types found in coastal marine waters and the variety of life history strategies fisheries species and nekton use in these environments. Thus, we focus our review on five selective but relevant topics, habitat templates, essential fish habitat, habitat mosaics/habitat connectivity, transitory/ephemeral habitat, and the emerging/maturing approaches to the study of fish-habitat systems as a roadmap to its development. We have highlighted selected important contributions in the progress made on each topic to better identify and quantify landscape scale interactions between living biota and structured habitats set within a dynamic landscape.
Temperature and Prey Species Richness Drive the Broad-Scale Distribution of a Generalist Predator
Authors: Michailidou Danai-Eleni , Lazarina Maria , Sgardelis Stefanos P.
Published: April 2021

The ongoing climate change and the unprecedented rate of biodiversity loss render the need to accurately project future species distributional patterns more critical than ever. Mounting evidence suggests that not only abiotic factors, but also biotic interactions drive broad-scale distributional patterns. Here, we explored the effect of predator-prey interaction on the predator distribution, using as target species the widespread and generalist grass snake (Natrix natrix). We used ensemble Species Distribution Modeling (SDM) to build a model only with abiotic variables (abiotic model) and a biotic one including prey species richness. Then we projected the future grass snake distribution using a modest emission scenario assuming an unhindered and no dispersal scenario. The two models performed equally well, with temperature and prey species richness emerging as the top drivers of species distribution in the abiotic and biotic models, respectively. In the future, a severe range contraction is anticipated in the case of no dispersal, a likely possibility as reptiles are poor dispersers. If the species can disperse freely, an improbable scenario due to habitat loss and fragmentation, it will lose part of its contemporary distribution, but it will expand northwards.
On the Locally Polynomial Complexity of the Projection-Gradient Method for Solving Piecewise Quadratic Optimisation Problems
Authors: Prusińska Agnieszka , Szkatuła Krzysztof , Tret’yakov Alexey
Published: April 2021

This paper proposes a method for solving optimisation problems involving piecewise quadratic functions. The method provides a solution in a finite number of iterations, and the computational complexity of the proposed method is locally polynomial of the problem dimension, i.e., if the initial point belongs to the sufficiently small neighbourhood of the solution set. Proposed method could be applied for solving large systems of linear inequalities.
Nonequilibrium Entropy Conservation and the Transport Equations of Mass, Momentum, and Energy
Authors: Peters Michael H.
Published: April 2021

Nonequilibrium statistical mechanics or molecular theory has put the transport equations of mass, momentum and energy on a firm or rigorous theoretical foundation that has played a critical role in their use and applications. Here, it is shown that those methods can be extended to nonequilibrium entropy conservation. As already known, the “closure” of the transport equations leads to the theory underlying the phenomenological laws, including Fick’s Law of Diffusion, Newton’s Law of Viscosity, and Fourier’s Law of Heat. In the case of entropy, closure leads to the relationship of entropy flux to heat as well as the Second Law or the necessity of positive entropy generation. It is further demonstrated how the complete set of transport equations, including entropy, can be simplified under physically restrictive assumptions, such as reversible flows and local equilibrium flows. This analysis, in general, yields a complete, rigorous set of transport equations for use in applications. Finally, it is also shown how this basis set of transport equations can be transformed to a new set of nonequilibrium thermodynamic functions, such as the nonequilibrium Gibbs’ transport equation derived here, which may have additional practical utility.
An Optimization Based Power Usage Scheduling Strategy Using Photovoltaic-Battery System for Demand-Side Management in Smart Grid
Authors: Ali Sajjad , Khan Imran , Jan Sadaqat , Hafeez Ghulam
Published: April 2021

Due to rapid population growth, technology, and economic development, electricity demand is rising, causing a gap between energy production and demand. With the emergence of the smart grid, residents can schedule their energy usage in response to the Demand Response (DR) program offered by a utility company to cope with the gap between demand and supply. This work first proposes a novel optimization-based energy management framework that adapts consumer power usage patterns using real-time pricing signals and generation from utility and photovoltaic-battery systems to minimize electricity cost, to reduce carbon emission, and to mitigate peak power consumption subjected to alleviating rebound peak generation. Secondly, a Hybrid Genetic Ant Colony Optimization (HGACO) algorithm is proposed to solve the complete scheduling model for three scenarios: without photovoltaic-battery systems, with photovoltaic systems, and with photovoltaic-battery systems. Thirdly, rebound peak generation is restricted by using Multiple Knapsack Problem (MKP) in the proposed algorithm. The presented model reduces the cost of using electricity, alleviates the peak load and peak-valley, mitigates carbon emission, and avoids rebound peaks without posing high discomfort to the consumers. To evaluate the applicability of the proposed framework comparatively with existing frameworks, simulations are conducted. The results show that the proposed HGACO algorithm reduced electricity cost, carbon emission, and peak load by 49.51%, 48.01%, and 25.72% in scenario I; by 55.85%, 54.22%, and 21.69% in scenario II, and by 59.06%, 57.42%, and 17.40% in scenario III, respectively, compared to without scheduling. Thus, the proposed HGACO algorithm-based energy management framework outperforms existing frameworks based on Ant Colony Optimization (ACO) algorithm, Particle Swarm Optimization (PSO) algorithm, Genetic Algorithm (GA), Hybrid Genetic Particle swarm Optimization (HGPO) algorithm.
A Two-Dimensional Partitioning of Fracture–Matrix Flow in Fractured Reservoir Rock Using a Dual-Porosity Percolation Model
Authors: Liu Jinhui , Zhou Yuli , Chen Jianguo
Published: April 2021

Fractures and micropores have varying contributions to the gas permeability of fractured reservoirs. The quantification of the contribution of fractures and micropores that form a dual-porosity system for gas permeability is critical when attempting to accurately evaluate gas production. However, due to insufficient knowledge of fracture–matrix flow partitioning in such dual-porosity systems, it is challenging for previous models to quantitatively characterize the fracture heterogeneity and accurately evaluate the gas flow and permeability in fractured rocks. In this study, we propose a dual-porosity percolation model to quantitatively investigate the contributions of fractures and matrix micropores towards the gas permeability of fractured rocks. Using percolation theory, we establish fracture networks with complex heterogeneity, which are characterized by various fracture densities and percolation probabilities within a porous matrix with various fracture/matrix permeability ratios. The compressible Navier–Stokes and Brinkman equations were adopted to describe the gas flow in the fractures and porous matrix, respectively. The simulation results indicate that the gas permeability of the dual-porosity system has an exponential relationship with the fracture density and matrix permeability. The contribution of fractures and matrix micropores toward gas permeability can be classified by establishing a two-dimensional partitioning of the fracture–matrix flow related to the fracture heterogeneity and fracture/matrix permeability ratio. The contribution of matrix micropores cannot be neglected if the fracture density is lower than a critical value.
Fault Analysis and Non-Redundant Fault Tolerance in 3-Level Double Conversion UPS Systems Using Finite-Control-Set Model Predictive Control
Authors: Caseiro Luís , Mendes André
Published: April 2021

Fault-tolerance is critical in power electronics, especially in Uninterruptible Power Supplies, given their role in protecting critical loads. Hence, it is crucial to develop fault-tolerant techniques to improve the resilience of these systems. This paper proposes a non-redundant fault-tolerant double conversion uninterruptible power supply based on 3-level converters. The proposed solution can correct open-circuit faults in all semiconductors (IGBTs and diodes) of all converters of the system (including the DC-DC converter), ensuring full-rated post-fault operation. This technique leverages the versatility of Finite-Control-Set Model Predictive Control to implement highly specific fault correction. This type of control enables a conditional exclusion of the switching states affected by each fault, allowing the converter to avoid these states when the fault compromises their output but still use them in all other conditions. Three main types of corrective actions are used: predictive controller adaptations, hardware reconfiguration, and DC bus voltage adjustment. However, highly differentiated corrective actions are taken depending on the fault type and location, maximizing post-fault performance in each case. Faults can be corrected simultaneously in all converters, as well as some combinations of multiple faults in the same converter. Experimental results are presented demonstrating the performance of the proposed solution.
Multilevel Factors Associated with Frailty among the Rural Elderly in Korea Based on the Ecological Model
Authors: Jang Ah Ram , Yoon Ju Young
Published: April 2021

Frailty is prevalent in the rural elderly and, as a result, they are vulnerable to serious health problems. The purpose of this study was to examine the multilevel factors affecting frailty among the rural elderly using the ecological model. A total of 386 participants aged 65 years or older from 60 rural areas were included in the study. Frailty was measured using the Cardiovascular Health Study frailty index. Multilevel logistic regression analysis was used to identify the factors affecting frailty among the rural elderly. The results show that the levels of prevalence for robust, pre-frailty, and frailty groups were 81 (21%), 216 (56%), and 89 (23%), respectively. As for intrapersonal factors, old age, lower than middle school education, low and moderate levels of physical activity, depressive symptoms, and cognitive dysfunction significantly increased the risk of frailty; however, no interpersonal and community factors were significant in affecting frailty. The findings indicate that individualized strategies to encourage physical activity, prevent depressive symptoms, and preserve cognitive function are needed to prevent frailty in the rural elderly.
Outdoor Playground Design Criteria Development for Early Childhood Development: A Delphi Study from the Perspective of Fundamental Movement Skills and Perceptual-Motor Skills
Authors: Jeon Heejun , Jun Sunhye
Published: April 2021

The purpose of this research is to discover adequate and environmental outdoor playground design criteria based on the collected opinions of experts. Taking the case of South Korea into account, this research focuses on the development of a new outdoor playground design criteria that could offset the limited motor activities and environmental use which has been restricted by the current regulations. In particular, this research approaches the issue from the perspective of children’s fundamental movement skills and the development of their perceptual-motor abilities. The research conducted three rounds of a Delphi survey and held a consensus of experts in child development, child physical education, and playground designs. The research achieved results defining 9 categories and 23 items within the categories of design criteria for outdoor playgrounds. Significantly, the discussions were not limited to children’s holistic development—from motor and physical development to attaining mental, social, and cognitive skills—but also included discussions of children’s dynamic interaction with the surrounding nature and environment, especially in challenge making and risk taking.