bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Cardiovascular Disease and Associated Factors Among Type 2 Diabetes Patients in Selected Hospitals of Harari Region, Eastern Ethiopia
Authors: Regassa Lemma Demissie , Tola Assefa , Ayele Yohanes
Published: February 2021

Background: Cardiovascular disease (CVD) is the most prevalent complication and the leading cause of death among patients with diabetes mellitus (DM). Type 2 diabetes mellitus (T2DM) patients have a 2- to 4-fold increased risk of CVD. There is a scarcity of data about the magnitude of CVD among patients with diabetes in Ethiopia. This study aimed to assess the prevalence and associated factors of CVD among T2DM patients at selected hospitals of Harari regional state of Ethiopia.

Methods: This hospital-based retrospective data review was conducted among T2DM patients on follow-up in the diabetes clinics of selected hospitals of Harari regional state. The records of T2DM patients who have been diagnosed between January 1, 2013, and December 31, 2017, were reviewed from March to April 2018. Data were collected by using structured checklists from all necessary documents of T2DM patients. Statistical analysis was done using STATA 14.1. Bivariate and multivariate logistic regressions were used to identify factors associated with CVD.

Result: The records of 454 T2DM patients were extracted from three government hospitals in Harari regional state. Their age was ranging from 15 to 86 years with a mean age (±SD) of 45.39 (14.76). The overall prevalence of CVD among T2DM patients was 42.51%, composed of hypertensive heart diseases (38.99%), heart failure (6.83%), and stroke (2.20%). The final multivariate logistic regression model revealed that age older than 60 years [adjusted odds ratio (AOR) = 3.22; 95% CI: 1.71–6.09], being physically inactive (AOR = 1.45; 95 CI: 1.06–2.38), drinking alcohol (AOR = 2.39; 95% CI: 1.17–6.06), hypertension (AOR = 2.41; 95% CI: 1.52–3.83), body mass index >24.9 kg/m2 (AOR = 1.81; 95% CI: 1.07–3.07), and experiencing microvascular diabetic complications (AOR = 3.62; 95% CI: 2.01–6.53) were significantly associated with the odds of having CVD.

Conclusion: The prevalence of CVD was high and associated with advanced age, physical inactivity, drinking alcohol, higher body mass index, hypertension, and having microvascular complications. Health care workers should educate T2DM patients about healthy lifestyles like physical activity, weight reduction, blood pressure control, and alcohol secession, which can reduce the risk of CVD.
Hemorrhagic Fever With Renal Syndrome in Vladivostok City, Russia
Authors: Yashina Liudmila N. , Hay John , Smetannikova Natalia A. , Kushnareva Tatiana V. , Iunikhina Olga V. , Kompanets Galina G.
Published: February 2021

Hemorrhagic fever with renal syndrome (HFRS) is a public health problem in Vladivostok city, Russia. From 1997 to 2019, a study of hantaviruses in Norway rats (Rattus norvegicus), a natural reservoir of Seoul virus (SEOV), and in HFRS patients was conducted. We demonstrated the presence of SEOV in the local population of Norway rats and detected SEOV in 10, Amur virus (AMRV) in 4 and Hantaan virus (HTNV) in 1 out of 15 HFRS patients. Genetic analysis based on partial S, M and L segment sequences revealed that the Russian SEOV strains were related most closely to strains from Cambodia and Vietnam. We postulate that the SEOV strains found in the port city of Vladivostok have been spread from South-East Asia as a result of distribution of rats during standard shipping trade activities. Moreover, we suggest that city residents may have acquired AMRV and HTNV infection during visits to rural areas.
Road Use Pattern and Street Crossing Habits of Schoolchildren in India
Authors: Tiwari Rajnarayan R. , Patel Shruti , Soju Annie , Trivedi Prarthana
Published: February 2021

Road traffic accidents (RTAs) contribute significant DALYs in the global burden of diseases. Vulnerable groups particularly pedestrians and children are at an increased risk. Road use pattern, street crossing habits, and road safety awareness are important determinants of RTAs. The present study was carried out to assess the road use pattern and street crossing habits of schoolchildren. This cross-sectional study included 497 schoolchildren of 12–15 years. The interview technique was used as a tool for data collection on a predesigned questionnaire. A total of 40.4% of schoolchildren did not like to go to school alone and wanted somebody from the family to drop them to school. About one quarter of the students were afraid of traffic and expressed their inability to deal with traffic on the road. A total of 10.7% reported crossing the street in groups, and 1.4% reported running while crossing the street. Only 80.9% of students received some form of road safety training, and the parents and schools were the major source of information for such safety training. Age <14 years and a lower level of mother's education were found to be significant contributors for poor road crossing habit in univariate as well as multivariate analysis. The study suggests that the knowledge regarding safe road use and street crossing was lacking among study participants albeit in a small proportion only. Safety aspects can be partly strengthened by imparting practical knowledge about road use pattern, street crossing habits, and road safety procedures.
What Are Poop Transplants and How Do They Work?
Authors: Patwardhan Sushmita , Diener Christian , Swegle Stephanie , Howsmon Becky , Gibbons Sean M.
Published: February 2021

Microbes are tiny creatures that live in and on our bodies. Many of them, especially those in the gut, help to keep us healthy. Sometimes, when we eat spoiled food or take antibiotics, we wipe out many of these good microbes. Usually, our good microbes recover from these disturbances, but sometimes harmful microbes can take their place and cause disease. Clostridioides difficile is a harmful microbe that causes severe diarrhea. Usually, antibiotics can kill C. difficile and return the gut to a healthy state, but in some cases, this microbe can come back again and again. Some people end up dying from these recurrent, antibiotic-resistant C. difficile infections. Recently, scientists have found that recurrent C. difficile can be cured by transplanting poop from a healthy person into a sick person. This process is called fecal microbiota transplantation (FMT) and it saves thousands of lives in the U.S. each year.
Effect of Age, Breed, and Sex on the Health-Related Quality of Life of Owner Assessed Healthy Dogs
Authors: Rodger Susan , Scott E Marian , Nolan Andrea , Wright Andrea K , Reid Jacqueline
Published: February 2021

Using an app, this exploratory study generated information on HRQL in a large cohort of dogs deemed healthy according to the owner. It forms the basis for further studies investigating the natural history of HRQL of dogs to inform the interpretation of interventional studies, but highlights the risks of relying on owner impression of health status. A previously published health-related quality of life (HRQL) instrument (VetMetrica™) that generates scores in four domains of quality of life in dogs - Energetic and Enthusiastic (E/E), Happy and Content (H/C), Active and Comfortable (A/C), and Calm and Relaxed (C/R), generated information on HRQL in 4,217 dogs (3 months−21 years). Dogs were categorized by age; young, 3–47 months, middle-aged, 48–95 months, and old, 96 months and older. Owners considered 2,959 dogs (3–95 months) to be “in perfect health” and these were used to explore the relationship between age, sex, breed and HRQL in apparently healthy dogs. Mean score was significantly greater (better) in young compared to middle-aged dogs in E/E, H/C and A/C and declined with advancing age. In H/C there was a small but significant difference in mean score between female and male dogs (mean greater in females), with a similar rate of decline in each gender with advancing age. In E/E there were very small but statistically significant differences in mean scores between certain breeds. In A/C there was a statistically significant interaction between breed and age and the rate of decline with advancing age differed with breed. Overall, age, breed, and sex predicted very little of the variation seen in HRQL scores. Data from a subset of 152 dogs, for whom clinical information was available, were used to examine the agreement between clinical evidence and owner opinion. According to the clinical records, 89 dogs were healthy and 63 had evidence of chronic disease. There was an approximately 40% disagreement between owner opinion on health status and clinical evidence of chronic disease (35% disagreement in all dogs and 43% in old dogs). HRQL scores were generally higher in dogs for whom there was no evidence of disease in the clinical record.
Dynamic Changes in the Expression of Interferon-Stimulated Genes in Joints of SPF Chickens Infected With Avian Reovirus
Authors: Wang Sheng , Xie Liji , Xie Zhixun , Wan Lijun , Huang Jiaoling , Deng Xianwen , Xie Zhi qin , Luo Sisi , Zeng Tingting , Zhang Yanfang , Zhang Minxiu , Zhou Lei
Published: February 2021

Avian reovirus (ARV) can induce many diseases as well as immunosuppression in chickens, severely endangering the poultry industry. Interferons (IFNs) play an antiviral role by inducing the expression of interferon-stimulated genes (ISGs). The effect of ARV infection on the expression of host ISGs is unclear. Specific-pathogen-free (SPF) chickens were infected with ARV strain S1133 in this study, and real time quantitative PCR was used to detect changes in the dynamic expression of IFNs and common ISGs in joints of SPF chickens. The results showed that the transcription levels of IFNA, IFNB, and several ISGs, including myxovirus resistance (MX), interferon-induced transmembrane protein 3 (IFITM3), protein kinase R (PKR), oligoadenylate synthase (OAS), interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), interferon-stimulated gene 12 (ISG12), virus inhibitory protein (VIPERIN), interferon-alpha-inducible protein 6 (IFI6), and integrin-associated protein (CD47), were upregulated in joints on days 1–7 of infection (the levels of increase of MX, IFIT5, OAS, VIPERIN, ISG12, and IFI6 were the most significant, at hundreds-fold). In addition, the expression levels of the ISGs encoding zinc finger protein 313 (ZFP313), and DNA damage–inducible transcript 4 (DDIT4) increased suddenly on the 1st or 2nd day, then decreased to control levels. The ARV viral load in chicken joints rapidly increased after 1 day of viral challenge, and the viral load remained high within 6 days of viral challenge. The ARV viral load sharply decreased starting on day 7. These results indicate that in SPF chicken joints, many ISGs have mRNA expression patterns that are basically consistent with the viral load in joints. IFNA, IFNB, and the ISGs MX, IFITM3, PKR, OAS, IFIT5, ISG12, VIPERIN, IFI6, and CD47 play important roles in defending against ARV invasion, inhibiting ARV replication and proliferation, and promoting virus clearance. These results enrich our understanding of the innate immune response mechanisms of hosts against ARV infection and provide a theoretical basis for prevention and control of ARV infection.
Effects of Nonlinearity and Network Architecture on the Performance of Supervised Neural Networks
Authors: Kulathunga Nalinda , Ranasinghe Nishath Rajiv , Vrinceanu Daniel , Kinsman Zackary , Huang Lei , Wang Yunjiao
Published: February 2021

The nonlinearity of activation functions used in deep learning models is crucial for the success of predictive models. Several simple nonlinear functions, including Rectified Linear Unit (ReLU) and Leaky-ReLU (L-ReLU) are commonly used in neural networks to impose the nonlinearity. In practice, these functions remarkably enhance the model accuracy. However, there is limited insight into the effects of nonlinearity in neural networks on their performance. Here, we investigate the performance of neural network models as a function of nonlinearity using ReLU and L-ReLU activation functions in the context of different model architectures and data domains. We use entropy as a measurement of the randomness, to quantify the effects of nonlinearity in different architecture shapes on the performance of neural networks. We show that the ReLU nonliearity is a better choice for activation function mostly when the network has sufficient number of parameters. However, we found that the image classification models with transfer learning seem to perform well with L-ReLU in fully connected layers. We show that the entropy of hidden layer outputs in neural networks can fairly represent the fluctuations in information loss as a function of nonlinearity. Furthermore, we investigate the entropy profile of shallow neural networks as a way of representing their hidden layer dynamics.
Tracking Changes on Soil Structure and Organic Carbon Sequestration after 30 Years of Different Tillage and Management Practices
Authors: Bienes Ramón , Marques Maria Jose , Sastre Blanca , García-Díaz Andrés , Esparza Iris , Antón Omar , Navarrete Luis , Hernánz José L. , Sánchez-Girón Víctor , Sánchez del Arco María J. , Alarcón Remedios
Published: February 2021

Long-term field trials are essential for monitoring the effects of sustainable land management strategies for adaptation and mitigation to climate change. The influence of more than thirty years of different management is analyzed on extensive crops under three tillage systems, conventional tillage (CT), minimum tillage (MT), and no-tillage (NT), and with two crop rotations, monoculture winter-wheat (Triticum aestivum L.) and wheat-vetch (Triticum aestivum L.-Vicia sativa L.), widely present in the center of Spain. The soil under NT experienced the largest change in organic carbon (SOC) sequestration, macroaggregate stability, and bulk density. In the MT and NT treatments, SOC content was still increasing after 32 years, being 26.5 and 32.2 Mg ha−1, respectively, compared to 20.8 Mg ha−1 in CT. The SOC stratification (ratio of SOC at the topsoil/SOC at the layer underneath), an indicator of soil conservation, increased with decreasing tillage intensity (2.32, 1.36, and 1.01 for NT, MT, and CT respectively). Tillage intensity affected the majority of soil parameters, except the water stable aggregates, infiltration, and porosity. The NT treatment increased available water, but only in monocropping. More water was retained at the permanent wilting point in NT treatments, which can be a disadvantage in dry periods of these edaphoclimatic conditions.
Photoperiod-Treatment in Mediterranean Bucks Can Improve the Reproductive Performance of the Male Effect Depending on the Extent of Their Seasonality
Authors: Zarazaga Luis A. , Gatica María Carolina , Delgado-Pertíñez Manuel , Hernández Horacio , Guzmán José Luis , Delgadillo José Alberto
Published: February 2021

This study examines the effectiveness of the photoperiod treatment (extra light for 88 days) to render the bucks sexually active during the seasonal anoestrous in order to induce a male effect, depending on the reproductive seasonality of the breed of the bucks used. In April, 57 anoestrous Blanca Andaluza does were distributed into four groups with three males each: 13 were exposed to control Murciano–Granadina bucks (lower seasonality); 15 were exposed to photostimulated Murciano–Granadina bucks; 14 were exposed to control Blanca Andaluza bucks (higher seasonality), and 15 were exposed to photostimulated Blanca Andaluza bucks. After male introduction, the sexual behaviour of the bucks was assessed, and harness marks recorded doe oestrous behaviour. Ovulation was confirmed from plasma progesterone, and the ovulation rate was assessed by transrectal ultrasonography. Fecundity, fertility, prolificacy and productivity were also determined. All of the does in all of the groups showed ovulation. Interaction between both sources of variation was observed: the percentage of females showing oestrous (p < 0.01) and productivity (p < 0.05) was the lowest in the Blanca Andaluza control group (50% and 0.36 ± 0.17 goat kids born/female, respectively). In conclusion, photoperiod-treated bucks efficiently induce a male effect, but photostimulation could be more necessary for breeds with deep seasonality.
Handling Associated with Drenching Does Not Impact Survival and General Health of Low Birth Weight Piglets
Authors: Van Tichelen Kevin , Prims Sara , Ayuso Miriam , Van Kerschaver Céline , Vandaele Mario , Degroote Jeroen , Van Cruchten Steven , Michiels Joris , Van Ginneken Chris
Published: February 2021

The increase in litter sizes in recent years has resulted in more low birth weight (LBW) piglets, accompanied by a higher mortality. A potential intervention to overcome this is drenching bioactive substances. However, if the act of drenching provokes additional stress in LBW piglets, it might counteract the supplement’s effect and be detrimental for the piglet’s survival. To study the effect of the drenching act, piglets from 67 sows were weighed within 4 h after birth. The mean litter birth weight (MLBW) and standard deviation (SD) were calculated. LBW piglets (n = 76) were defined as weighing between (MLBW-1*SD) and (MLBW-2.5*SD). They were randomly allocated to two treatments: “sham” (conducting the act of drenching by inserting an empty 2.5 mL syringe in the mouth during 20 s, once a day, d1 till d7; n = 37) or “no treatment” (no handling; n = 39). On day 1, 3, 9, 24 and 38, piglets were weighed and scored for skin lesions. Blood samples were collected on day 9 and 38 and analyzed to determine glucose, non-esterified fatty acids (NEFA), urea, immunoglobulin G (IgG), insulin-like growth factor 1 (IGF-1) and a standard blood panel test. There was no difference between sham drenched and untreated piglets regarding any of the parameters. In conclusion, this study showed that drenching does not impose a significant risk to LBW piglets and can be applied safely during the first 7 days after birth.
Analysis of the Sustainability of Fattening Systems for Iberian Traditional Pig Production through a Technical and Environmental Approach
Authors: García-Gudiño Javier , Blanco-Penedo Isabel , Font-i-Furnols Maria , Angón Elena , Perea José Manuel
Published: February 2021

At present, two types of fattening are carried out in Iberian traditional pig production. The montanera is the fattening system where fatteners are fed on acorns and pasture in the dehesa, and cebo de campo is the fattening where the pigs are fed on compound feed and natural resources, mainly pasture. The aim of this paper is to analyze Iberian fattening production from an economic and environmental approach in order to identify fattening strategies to increase the sustainability of this traditional livestock activity. Based on technical-economic and environmental variables, the differences between Iberian farms according to the types of fattening were determined using discriminant analysis techniques. The model based on environmental variables showed a greater predictive ability than that found in the model based on technical-economic variables. Consequently, environmental variables can be used as reference points to classify the Iberian farms according to the type of fattening. Furthermore, canonical correlation analysis allowed to study the relationships between both sets of variables, showing that environmental values had a strong correlation with technical-economic variables. The results of this study show that it is possible to improve the sustainability of Iberian traditional pig production through fattening strategies in both types of fattening.
Ambient Noise Measurements to Constrain the Geological Structure of the Güevéjar Landslide (S Spain)
Authors: Delgado José , Galiana-Merino Juan José , García-Tortosa Francisco J. , Garrido Jesús , Lenti Luca , Martino Salvatore , Peláez José A. , Rodríguez-Peces Martín J. , de Galdeano Carlos Sanz , Soler-Llorens Juan L.
Published: February 2021

The reactivation of very large landslides may cause severe damage to society. Its prevention and management requires detailed information on the geometry and structure of these landslides, but the use of standard techniques (boreholes) may be prohibitive from an economic point of view. To overcome these difficulties, geophysical techniques are of special interest because they allow for studying very large areas at a reasonable cost. In this paper, we present a case study wherein the analysis of ambient noise allowed us to produce a model of a large landslide near Granada (southern Spain). The geometry and location of the failure zone, as well as the assessment of the state of involved materials, were estimated by combining two available boreholes and different geophysical techniques (downhole tests and the spectral analysis of ambient noise, horizontal to vertical spectral ratios (HVSR) and the frequency-wavenumber (f-k) methods). The results have allowed us to differentiate between values within the landslide mass with respect to those of stable materials, and to perform for the first time a comprehensive geological model of this unstable mass. Differences were also observed within the landslide mass (earth flow vs. slide zones), which are attributed to differences in the degree of alteration and the disturbance of the internal structure of materials constituting the landslide mass. These results show that techniques based on the measurement of ambient noise are of special interest for studying very large, highly remolded landslide masses.
Art as Critique under Neoliberalism: Negativity Undoing Economic Naturalism
Authors: Gawronski Alexander
Published: February 2021

This essay considers the possibilities of contemporary art as a viable medium of socio-political critique within a cultural terrain dominated by naturalised neoliberal economics. It begins by considering the centrality of negativity to the historical project of critical theory most forcefully pursued by Adorno as ‘negative dialectics.’ Subsequent varieties of postmodern critique fairly dispensed with dialectics variously favouring complexity and an overriding emphasis on textuality. With the birth of neoliberalism and its burgeoning emphasis on ‘the contemporary’, economic values begin to penetrate every aspect of contemporary life and experience, including art and culture. Contemporary capitalism dematerialised as financialisation now comprises a naturalised ambience that is both everywhere and nowhere. Capitalist ambience is echoed in contemporary art that suggests criticality and yet seems to side with the imagery, values and logics of the prevailing financial order. The naturalisation of the neoliberal order is further internalised by artists online. Exacerbated contemporary emphasis on the ‘self as entrepreneur’ coincides with the biopolitical transformation of the contemporary artist into an individual ‘enterprise unit’. This is particularly observable online on social media where an artist’s whole life is simultaneously the subject and object of art. Criticality in art does not disappear but becomes ‘self-annulling’: it acts as a conduit questioning the commodity-identity of art while pointing to phenomena and affects outside the art world. With the recent appearance of the COVID-19 virus, added to the unignorable impact of global climate change, ‘real nature’ assumes a critical role, undermining neoliberalism’s ideological naturalisation while laying-bare the extent of its structural contradictions. Art criticality is revivified by divesting from art contexts saturated with neoliberal imperatives. Criticality is negatively practiced as an ‘un-’ or ‘not-doing’, defining modes of exodus while, crucially, not abandoning art’s institutional definition altogether.
Editorial of Special Issue “Health Impact Assessment of Air Pollution”
Authors: Krzyzanowski Michal
Published: February 2021

It is well recognized that air pollution affects health [...]
Cardiopulmonary and Neurologic Dysfunctions in Fibrodysplasia Ossificans Progressiva
Authors: Khan Fatima , Yu Xiaobing , Hsiao Edward C.
Published: February 2021

Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare but debilitating disorder characterized by spontaneous, progressive, and irreversible heterotopic ossifications (HO) at extraskeletal sites. FOP is caused by gain-of-function mutations in the Activin receptor Ia/Activin-like kinase 2 gene (Acvr1/Alk2), with increased receptor sensitivity to bone morphogenetic proteins (BMPs) and a neoceptor response to Activin A. There is extensive literature on the skeletal phenotypes in FOP, but a much more limited understanding of non-skeletal manifestations of this disease. Emerging evidence reveals important cardiopulmonary and neurologic dysfunctions in FOP including thoracic insufficiency syndrome, pulmonary hypertension, conduction abnormalities, neuropathic pain, and demyelination of the central nervous system (CNS). Here, we review the recent research and discuss unanswered questions regarding the cardiopulmonary and neurologic phenotypes in FOP.
Early Adolescence Prefrontal Cortex Alterations in Female Rats Lacking Dopamine Transporter
Authors: Illiano Placido , Leo Damiana , Gainetdinov Raul R. , Pardo Marta
Published: February 2021

Monoamine dysfunctions in the prefrontal cortex (PFC) can contribute to diverse neuropsychiatric disorders, including ADHD, bipolar disorder, PTSD and depression. Disrupted dopamine (DA) homeostasis, and more specifically dopamine transporter (DAT) alterations, have been reported in a variety of psychiatric and neurodegenerative disorders. Recent studies using female adult rats heterozygous (DAT+/−) and homozygous (DAT−/−) for DAT gene, showed the utility of those rats in the study of PTSD and ADHD. Currently, a gap in the knowledge of these disorders affecting adolescent females still represents a major limit for the development of appropriate treatments. The present work focuses on the characterization of the PFC function under conditions of heterozygous and homozygous ablation of DAT during early adolescence based on the known implication of DAT and PFC DA in psychopathology during adolescence. We report herein that genetic ablation of DAT in the early adolescent PFC of female rats leads to changes in neuronal and glial cell homeostasis. In brief, we observed a concurrent hyperactive phenotype, accompanied by PFC alterations in glutamatergic neurotransmission, signs of neurodegeneration and glial activation in DAT-ablated rats. The present study provides further understanding of underlying neuroinflammatory pathological processes that occur in DAT-ablated female rats, what can provide novel investigational approaches in human diseases.
Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia
Authors: Vial Jean Philippe , Lechevalier Nicolas , Lacombe Francis , Dumas Pierre-Yves , Bidet Audrey , Leguay Thibaut , Vergez François , Pigneux Arnaud , Béné Marie C.
Published: February 2021

The assessment of minimal residual disease (MRD) is increasingly considered to monitor response to therapy in hematological malignancies. In acute myeloblastic leukemia (AML), molecular MRD (mMRD) is possible for about half the patients while multiparameter flow cytometry (MFC) is more broadly available. However, MFC analysis strategies are highly operator-dependent. Recently, new tools have been designed for unsupervised MFC analysis, segregating cell-clusters with the same immunophenotypic characteristics. Here, the Flow-Self-Organizing-Maps (FlowSOM) tool was applied to assess MFC-MRD in 96 bone marrow (BM) follow-up (FU) time-points from 40 AML patients with available mMRD. A reference FlowSOM display was built from 19 healthy/normal BM samples (NBM), then simultaneously compared to the patient’s diagnosis and FU samples at each time-point. MRD clusters were characterized individually in terms of cell numbers and immunophenotype. This strategy disclosed subclones with varying immunophenotype within single diagnosis and FU samples including populations absent from NBM. Detectable MRD was as low as 0.09% in MFC and 0.051% for mMRD. The concordance between mMRD and MFC-MRD was 80.2%. MFC yielded 85% specificity and 69% sensitivity compared to mMRD. Unsupervised MFC is shown here to allow for an easy and robust assessment of MRD, applicable also to AML patients without molecular markers.
The Prognostic Value of the De Ritis Ratio for Progression-Free Survival in Patients with NET Undergoing [177Lu]Lu-DOTATOC-PRRT: A Retrospective Analysis
Authors: Ruhwedel Tristan , Rogasch Julian M. M. , Huang Kai , Jann Henning , Schatka Imke , Furth Christian , Amthauer Holger , Wetz Christoph
Published: February 2021

Background: The De Ritis ratio (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) has demonstrated prognostic value in various cancer entities. We evaluated the prognostic capability of the De Ritis ratio in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). Methods: Unicentric, retrospective analysis of 125 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC (female: 37%; median age: 66 years; G1+G2 NET: 95%). The prognostic value regarding progression-free survival (PFS) was analyzed with univariable and multivariable Cox regression. Prognostic accuracy was determined with Harrell’s C index and a likelihood ratio test. Results: Progression, relapse, or death after PRRT was observed in 102/125 patients. Median progression-free survival (PFS) was 15.8 months. Pancreatic or pulmonary origin, high De Ritis ratio, and high Chromogranin A (CgA) significantly predicted shorter PFS in univariable Cox. In multivariable Cox regression, only high De Ritis ratio >0.927 (HR: 1.7; p = 0.047) and high CgA >twice the upper normal limit (HR: 2.1; p = 0.005) remained independent predictors of shorter PFS. Adding the De Ritis ratio to the multivariable Cox model (age, Eastern Cooperative Oncology Group (ECOG) performance status, primary origin, CgA) significantly improved prognostic accuracy (p < 0.001). Conclusions: The De Ritis ratio is simple to obtain in clinical routine and can provide independent prognostic value for PFS in patients with NET undergoing PRRT.
NRF2 Activation Confers Resistance to eIF4A Inhibitors in Cancer Therapy
Authors: Sanghvi Viraj R. , Mohan Prathibha , Singh Kamini , Cao Linlin , Berishaj Marjan , Wolfe Andrew L. , Schatz Jonathan H. , Lailler Nathalie , de Stanchina Elisa , Viale Agnes , Wendel Hans-Guido
Published: February 2021

Inhibition of the eIF4A RNA helicase with silvestrol and related compounds is emerging as a powerful anti-cancer strategy. We find that a synthetic silvestrol analogue (CR-1-31 B) has nanomolar activity across many cancer cell lines. It is especially active against aggressive MYC+/BCL2+ B cell lymphomas and this likely reflects the eIF4A-dependent translation of both MYC and BCL2. We performed a genome-wide CRISPR/Cas9 screen and identified mechanisms of resistance to this new class of therapeutics. We identify three negative NRF2 regulators (KEAP1, CUL3, CAND1) whose inactivation is sufficient to cause CR1-31-B resistance. NRF2 is known to alter the oxidation state of translation factors and cause a broad increase in protein production. We find that NRF2 activation particularly increases the translation of some eIF4A-dependent mRNAs and restores MYC and BCL2 production. We know that NRF2 functions depend on removal of sugar adducts by the frutosamine-3-kinase (FN3K). Accordingly, loss of FN3K results in NRF2 hyper-glycation and inactivation and resensitizes cancer cells to eIF4A inhibition. Together, our findings implicate NRF2 in the translation of eIF4A-dependent mRNAs and point to FN3K inhibition as a new strategy to block NRF2 functions in cancer.
Safety and Efficacy of Weekly Paclitaxel and Cisplatin Chemotherapy for Ovarian Cancer Patients with Hypersensitivity to Carboplatin
Authors: Tate Shinichi , Nishikimi Kyoko , Matsuoka Ayumu , Otsuka Satoyo , Shozu Makio
Published: February 2021

Background: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). Methods: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed carboplatin HSR during previous chemotherapy (carboplatin and paclitaxel) at our institution between 2011 and 2019. After premedication was administered, paclitaxel was administered over 1 h, followed by cisplatin over 1 h (paclitaxel 80 mg/m2; cisplatin 25 mg/m2; 1, 8, 15 day/4 weeks). We investigated the incidence of patients who successfully received wTP for at least one cycle, treatments compliance, progression-free survival (PFS), and overall survival (OS). Results: The median number of wTP administration cycles was 4 (Interquartile Range IQR, 3–7), 71 patients (83%) successfully received wTP, and 15 patients (17%) developed cisplatin HSR. The efficacy of treatment was as follows: 55 (64%) patients completed the scheduled wTP, 9 (10%) patients discontinued due to HSR to cisplatin within 6 cycles, 1 (1%) patient discontinued due to renal toxicity (grade 2) at the 6th cycle, and 21 (24%) patients discontinued due to progressive disease within 6 cycles. The median PFS and OS after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95% CI: 19.0–50.2), respectively. Conclusions: wTP was safe and well-tolerated in patients who developed carboplatin HSR.
Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression
Authors: Rigiracciolo Damiano Cosimo , Cirillo Francesca , Talia Marianna , Muglia Lucia , Gutkind Jorge Silvio , Maggiolini Marcello , Lappano Rosamaria
Published: February 2021

Breast cancer represents the most common diagnosed malignancy and the main leading cause of tumor-related death among women worldwide. Therefore, several efforts have been made in order to identify valuable molecular biomarkers for the prognosis and prediction of therapeutic responses in breast tumor patients. In this context, emerging discoveries have indicated that focal adhesion kinase (FAK), a non-receptor tyrosine kinase, might represent a promising target involved in breast tumorigenesis. Of note, high FAK expression and activity have been tightly correlated with a poor clinical outcome and metastatic features in several tumors, including breast cancer. Recently, a role for the integrin-FAK signaling in mechanotransduction has been suggested and the function of FAK within the breast tumor microenvironment has been ascertained toward tumor angiogenesis and vascular permeability. FAK has been also involved in cancer stem cells (CSCs)-mediated initiation, maintenance and therapeutic responses of breast tumors. In addition, the potential of FAK to elicit breast tumor-promoting effects has been even associated with the capability to modulate immune responses. On the basis of these findings, several agents targeting FAK have been exploited in diverse preclinical tumor models. Here, we recapitulate the multifaceted action exerted by FAK and its prognostic significance in breast cancer. Moreover, we highlight the recent clinical evidence regarding the usefulness of FAK inhibitors in the treatment of breast tumors.
Amphiregulin Regulates Melanocytic Senescence
Authors: Pommer Michaela , Kuphal Silke , Bosserhoff Anja K.
Published: February 2021

Oncogene-induced senescence (OIS) is a decisive process to suppress tumor development, but the molecular details of OIS are still under investigation. Using an established OIS model of primary melanocytes transduced with BRAF V600E and compared to control cells, amphiregulin (AREG) was shown to be induced. In addition, AREG expression was observed in nevi, which by definition, are senescent cell clusters, compared to melanocytes. Interestingly, treatment of melanocytes with recombinant AREG did induce senescence. This led to the assumption that extracellular AREG has an important function in this process. Inhibition of the epidermal growth factor receptor (EGFR) using Gefitinib identified AREG as one of EGFR ligands responsible for senescence. Furthermore, depletion of AREG expression in senescent BRAF V600E melanocytes resulted in a significant reduction of senescent melanocytes. This study reveals AREG as an essential molecular component of signaling pathways leading to senescence in melanocytes.
Genetic Abnormalities in Multiple Myeloma: Prognostic and Therapeutic Implications
Authors: Cardona-Benavides Ignacio J. , de Ramón Cristina , Gutiérrez Norma C.
Published: February 2021

Some genetic abnormalities of multiple myeloma (MM) detected more than two decades ago remain major prognostic factors. In recent years, the introduction of cutting-edge genomic methodologies has enabled the extensive deciphering of genomic events in MM. Although none of the alterations newly discovered have significantly improved the stratification of the outcome of patients with MM, some of them, point mutations in particular, are promising targets for the development of personalized medicine. This review summarizes the main genetic abnormalities described in MM together with their prognostic impact, and the therapeutic approaches potentially aimed at abrogating the undesirable pathogenic effect of each alteration.
Seeing and Overcoming the Complexities of Intersectionality
Authors: Thomas Cate , MacMillan Colleen , McKinnon Merryn , Torabi Hayley , Osmond-McLeod Megan , Swavley Ellen , Armer Tamzen , Doyle Kimberley
Published: February 2021

Background: Intersectionality contests that individuals have multiple characteristics in their identity that cannot be siloed or deemed exclusive to each other. Understanding and utilising an intersectional lens in organisations can increase inclusion of individuals and organisational performance. An educational package known as the Intersectionality Walk (IW) was developed by the authors, piloted, and evaluated in order to break down the commonly held descriptors of diversity silos that fragments inclusion, and to understand how various identity characteristics compound disadvantage. The paper outlines the need to transition from siloed views of diversity to a more intrinsic view of identity to achieve inclusivity. Methods: The IW was developed and trialled with a series of work-based scenarios and realistic multifaceted personas. Data collection occurred pre- and post-IW utilising a mixed methods approach. Responses to Likert scale surveys and open-ended questions were captured and analysed via inductive and grounded theory perspectives. Results: An improved awareness and understanding of individual knowledge, reflectivity and positionality relating to intersectionality and intersectional approaches was reported on completion of the IW. Furthermore, responses reported how and why organisations can approach and improve inclusivity via using intersectional approaches. Conclusions: The IW as an educational package has a positive impact and is a key linkage for all employers to build an inclusive culture and to harness the talent of all employees. Further research will occur to measure the implemented change in organisations following the IW.
Development of Iron-Doped Hydroxyapatite Coatings
Authors: Predoi Daniela , Iconaru Simona Liliana , Ciobanu Steluta Carmen , Predoi Silviu-Adrian , Buton Nicolas , Megier Christelle , Beuran Mircea
Published: February 2021

It is known that iron is found as a trace element in bone tissue, the main inorganic constituent of which is hydroxyapatite. Therefore, iron-doped hydroxyapatite (HApFe) materials could be new alternatives for many biomedical applications. A facile dip coating process was used to elaborate the iron-doped hydroxyapatite (HApFe) nanocomposite coatings. The HApFe suspension used to prepare the coatings was achieved using a co-precipitation method, which was adapted in the laboratory. The quality of the HApFe suspension was assessed through dynamic light scattering (DLS), ultrasonic measurements, and zeta potential values. The hydroxyapatite XRD patterns were observed in the HApFe nanocomposite with no significant shifting of peak positions, thus suggesting that the incorporation of iron did not significantly modify the hydroxyapatite structure. The morphology of the HApFe nanoparticles was evaluated using transmission electron microscopy (TEM). Scanning electron microscopy (SEM) was used in order to investigate the morphologies of HApFe particles and coatings, while their chemical compositions were assessed using energy-dispersive X-ray spectroscopy (EDS). The SEM results suggested that the HApFe consists mainly of spherical nanometric particles and that the surfaces of the coatings are continuous and homogeneous. Additionally, the EDS spectra highlighted the purity of the samples and confirmed the presence of calcium, phosphorous, and iron in the analyzed sample. The in vitro cytotoxicity of the HApFe suspensions and coatings was evidenced using osteoblast cells. The MTT assay showed that both the HApFe suspensions and coatings exhibited biocompatible properties.
Prediction of Friction Degradation in Highways with Linear Mixed Models
Authors: Santos Adriana , Freitas Elisabete F. , Faria Susana , Oliveira Joel R. M. , Rocha Ana Maria A. C.
Published: February 2021

The development of a linear mixed model to describe the degradation of friction on flexible road pavements to be included in pavement management systems is the aim of this study. It also aims at showing that, at the network level, factors such as temperature, rainfall, hypsometry, type of layer, and geometric alignment features may influence the degradation of friction throughout time. A dataset from six districts of Portugal with 7204 sections was made available by the Ascendi Concession highway network. Linear mixed models with random effects in the intercept were developed for the two-level and three-level datasets involving time, section and district. While the three-level models are region-specific, the two-level models offer the possibility to be adopted to other areas. For both levels, two approaches were made: One integrating into the model only the variables inherent to traffic and climate conditions and the other including also the factors intrinsic to the highway characteristics. The prediction accuracy of the model was improved when the variables hypsometry, geometrical features, and type of layer were considered. Therefore, accurate predictions for friction evolution throughout time are available to assist the network manager to optimize the overall level of road safety.
Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series
Authors: Elkrief Arielle , Kazandjian Suzanne , Alcindor Thierry
Published: February 2021

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.
Computation in Complex Networks
Authors: Pizzuti Clara , Socievole Annalisa
Published: February 2021

The Special Issue on “Computation in Complex Networks” focused on gathering highly original papers in the field of current complex network research [...]
A New Family of Continuous Probability Distributions
Authors: El-Morshedy M. , Alshammari Fahad Sameer , Hamed Yasser S. , Eliwa Mohammed S. , Yousof Haitham M.
Published: February 2021

In this paper, a new parametric compound G family of continuous probability distributions called the Poisson generalized exponential G (PGEG) family is derived and studied. Relevant mathematical properties are derived. Some new bivariate G families using the theorems of “Farlie-Gumbel-Morgenstern copula”, “the modified Farlie-Gumbel-Morgenstern copula”, “the Clayton copula”, and “the Renyi’s entropy copula” are presented. Many special members are derived, and a special attention is devoted to the exponential and the one parameter Pareto type II model. The maximum likelihood method is used to estimate the model parameters. A graphical simulation is performed to assess the finite sample behavior of the estimators of the maximum likelihood method. Two real-life data applications are proposed to illustrate the importance of the new family.
Safety Bubbles: A Review of the Proposed Functions of Froth Nesting among Anuran Amphibians
Authors: Gould John
Published: February 2021

The adults of several anuran amphibian species deposit their eggs externally in mucus secretions that are purposely aerated to produce a froth nest. This type of clutch structure has evolved independently several times in this group and has been proposed to serve a variety and often simultaneous adaptive functions associated with protecting offspring from sub-optimal conditions during embryogenesis and later stages after hatching has occurred. These functions range from buffering offspring from sub-optimal temperatures and desiccation, to defending against predation and improving oxygenation. This versatility has likely helped facilitate the reduced reliance of egg development on water and thus the penetration of anurans into environments where permanent aquatic systems are not always available. In this paper, I review the hypothesised functions of the anuran froth nest as a mucus-based solution to the environmental challenges offspring face during development, with consideration of the functions of froth nest breakdown and communal froth nesting, as well.
Temporary Water Holes May Benefit the Breeding of the Common Skipper Frog Euphlyctis cyanophlyctis (Anura: Dicroglossidae)
Authors: Chowdhury Mohammad Abdul Wahed , Shil Shimu Rani , Rahman Md. Mizanur
Published: February 2021

Seasonal fluctuations in adult Euphlyctis cyanophlyctis density were recorded in two permanent ponds in Southeastern Bangladesh. From a two-year dataset of seven habitat parameters, the seasonal suitability of two different pond habitats was examined to understand these fluctuations of frog density. The combined influence of the parameters on the density was significant in all three seasons. One combination was found to be optimal: water temperature of 24 °C, a pH of approximately 6, and a water depth of 2.29 m. These conditions supported more than 24 frogs per acre in the round pond. In the forestry pond, the optimal parameters were a water temperature of 27 °C and a water depth of less than 1 m, which accommodated 27 frogs per acre. The result indicates that a slight increase in any of these parameters was found to sharply lower the accommodation capacity of the studied ponds to less than half of the aforesaid densities, especially in the rainy season. During this season, the adults were found to breed in the small waterholes adjacent to the ponds. This may be the response of anuran to temporal unsuitability, for example, the depth of water and the pH of the permanent ponds.