bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Unfounded Enthusiasm for Soft Selective Sweeps III: The Supervised Machine Learning Algorithm That Isn’t
Authors: Elhaik Eran , Graur Dan
Published: April 2021

In the last 15 years or so, soft selective sweep mechanisms have been catapulted from a curiosity of little evolutionary importance to a ubiquitous mechanism claimed to explain most adaptive evolution and, in some cases, most evolution. This transformation was aided by a series of articles by Daniel Schrider and Andrew Kern. Within this series, a paper entitled “Soft sweeps are the dominant mode of adaptation in the human genome” (Schrider and Kern, Mol. Biol. Evolut. 2017, 34(8), 1863–1877) attracted a great deal of attention, in particular in conjunction with another paper (Kern and Hahn, Mol. Biol. Evolut. 2018, 35(6), 1366–1371), for purporting to discredit the Neutral Theory of Molecular Evolution (Kimura 1968). Here, we address an alleged novelty in Schrider and Kern’s paper, i.e., the claim that their study involved an artificial intelligence technique called supervised machine learning (SML). SML is predicated upon the existence of a training dataset in which the correspondence between the input and output is known empirically to be true. Curiously, Schrider and Kern did not possess a training dataset of genomic segments known a priori to have evolved either neutrally or through soft or hard selective sweeps. Thus, their claim of using SML is thoroughly and utterly misleading. In the absence of legitimate training datasets, Schrider and Kern used: (1) simulations that employ many manipulatable variables and (2) a system of data cherry-picking rivaling the worst excesses in the literature. These two factors, in addition to the lack of negative controls and the irreproducibility of their results due to incomplete methodological detail, lead us to conclude that all evolutionary inferences derived from so-called SML algorithms (e.g., S/HIC) should be taken with a huge shovel of salt.
Intragenic Deletions in FLNB Are Part of the Mutational Spectrum Causing Spondylocarpotarsal Synostosis Syndrome
Authors: Fukushima Kaya , Parthasarathy Padmini , Wade Emma M. , Morgan Tim , Gowrishankar Kalpana , Markie David M. , Robertson Stephen P.
Published: April 2021

Spondylocarpotarsal synostosis syndrome (SCT) is characterized by vertebral fusions, a disproportionately short stature, and synostosis of carpal and tarsal bones. Pathogenic variants in FLNB, MYH3, and possibly in RFLNA, have been reported to be responsible for this condition. Here, we present two unrelated individuals presenting with features typical of SCT in which Sanger sequencing combined with whole genome sequencing identified novel, homozygous intragenic deletions in FLNB (c.1346-1372_1941+389del and c.3127-353_4223-1836del). Both deletions remove several consecutive exons and are predicted to result in a frameshift. To our knowledge, this is the first time that large structural variants in FLNB have been reported in SCT, and thus our findings add to the classes of variation that can lead to this disorder. These cases highlight the need for copy number sensitive methods to be utilized in order to be comprehensive in the search for a molecular diagnosis in individuals with a clinical diagnosis of SCT.
Accessibility, Natural User Interfaces and Interactions in Museums: The IntARSI Project
Authors: Pietroni Eva , Pagano Alfonsina , Biocca Luigi , Frassineti Giacomo
Published: April 2021

In a museum context, people have specific needs in terms of physical, cognitive, and social accessibility that cannot be ignored. Therefore, we need to find a way to make art and culture accessible to them through the aid of Universal Design principles, advanced technologies, and suitable interfaces and contents. Integration of such factors is a priority of the Museums General Direction of the Italian Ministry of Cultural Heritage, within the wider strategy of museum exploitation. In accordance with this issue, the IntARSI project, publicly funded, consists of a pre-evaluation and a report of technical specifications for a new concept of museology applied to the new Museum of Civilization in Rome (MuCIV). It relates to planning of multimedia, virtual, and mixed reality applications based on the concept of “augmented” and multisensory experience, innovative tangible user interfaces, and storytelling techniques. An inclusive approach is applied, taking into account the needs and attitudes of a wide audience with different ages, cultural interests, skills, and expectations, as well as cognitive and physical abilities.
Health Service Access among Indonesian Migrant Domestic Workers in Taiwan
Authors: Weng Shuen-Fu , Malik Azis , Wongsin Utoomporn , Lohmeyer Franziska Michaela , Lin Li-Fong , Atique Suleman , Jian Wen-Shan , Gusman Yuherina , Iqbal Usman
Published: April 2021

The number of migrant workers in Taiwan increases annually. The majority is from Indonesia and most of them are female caregivers. This study aims to determine the access to health services and the associated factors among Indonesian female domestic workers in Taiwan. In this cross-sectional study, data were collected from February to May 2019, using a structured questionnaire. Subsequently, multiple logistic regression was used to examine the association between socio-demographic factors and health service access. Two hundred and eighty-four domestic migrant workers were interviewed. Eighty-five percent of the respondents declared sickness at work, but only 48.8% seek health care services. Factors associated with health service access were marital status, income, and the availability of an attendant to accompany the migrant workers to the healthcare facilities. Language barrier and time flexibility were the main obstacles. Further research and an effective health service policy are needed for the domestic migrant workers to better access health care services.
Home-Advantage during COVID-19: An Analysis in Portuguese Football League
Authors: Matos Rui , Monteiro Diogo , Antunes Raul , Mendes Diogo , Botas João , Clemente João , Amaro Nuno
Published: April 2021

Covid-19 pandemic forced, at the final rounds of 2019–2020 season, in many different sport leagues worldwide, teams to play without an audience. Therefore, the present paper aims to compare the home advantage score in the last ten rounds in 2019–2020 season with the first 24 rounds in same season using Pollard’s (1986) and Matos et al.’s (2020) methods. In addition, comparisons across different seasons (2016–2017; 2017–2018; 2018–2019 and 2019–2020) using the same methods were also analyzed. Results showed no differences (p > 0.05) between first 24 rounds and the last 10 in 2019–2020 season as well as in the 3 previous seasons. With Pollard’s method, no differences (p > 0.05) were also found among those four seasons on global (all 34 rounds) home advantage. However, a significance difference between 2017–2018 and 2019–2020 (p < 0.05) was founded using Matos et al.’s (2020) method, which is an indicator of the importance of using complementary methods when analyzing the same realities. Overall, despite what might be expectable from recent findings, the lack of an audience in the last 10 rounds of Portuguese Football League 2019–2020 season, due to COVID-19 pandemic, did not affect home advantage. Therefore, future studies could try to analyze other different variables in Portuguese Football League, such as referees’ behaviors, rules changing (e.g., the possibility of making five substitutions, instead of three), crowd dimension and density as well as include variables about odds as forecasts in football being played without crowds.
“The Power of a Firm’s Benevolent Act”: The Influence of Work Overload on Turnover Intention, the Mediating Role of Meaningfulness of Work and the Moderating Effect of CSR Activities
Authors: Hwang Yun-Seok , Kim Byung-Jik
Published: April 2021

Although previous works have examined how work overload affects the perceptions, attitudes, and behaviors of members in an organization, those studies have paid insufficient attention to the mediating and contingent factors in the work overload–turnover intention link from the perspective of positive psychology. Considering the theoretical and practical value and importance of positive psychology, studies that use it to investigate underlying processes are needed. Also, existing studies on work overload have focused on the moderating role of individual-level variables to reduce the negative effects of work overload, mostly ignoring the importance of organizational-level moderators. To resolve those issues, we hypothesize that the meaningfulness of an employee’s work mediates the relationship between work overload and turnover intention. Corporate social responsibility (CSR) practices could moderate the association between work overload and the meaningfulness of work. Using a three-wave data set gathered from 356 currently working employees in South Korea, we reveal not only that the meaningfulness of work mediates the work overload–turnover intention link, but also that CSR activities play a buffering role in the work overload–meaningfulness of work link. Our findings suggest that, from the perspective of positive psychology, the degree of meaningfulness of work (as a mediator) and CSR activities (as a moderator) function as intermediating mechanisms in the work overload–turnover intention link.
Running Performance Variability among Runners from Different Brazilian States: A Multilevel Approach
Authors: Thuany Mabliny , Gomes Thayse Natacha , Hill Lee , Rosemann Thomas , Knechtle Beat , Almeida Marcos B.
Published: April 2021

The ecological model theory highlights that human development (or a given behavior) is the result of the interaction of variables derived from different levels, comprising those directly related to the subjects and those related to the environment. Given that, the purpose of this study is to establish whether runners’ performance may vary among different Brazilian states, as the factors associated with this difference. The sample comprised 1151 Brazilian runners (61.8% men) that completed an online questionnaire, providing information about biological (sex, age, height, and weight), training (running pace, frequency and volume/week, and motivation), sociodemographic (place of residence and wage) aspects, and perceptions about the environmental influences on the practice. Information about state variables was obtained from official institutes, and comprised the human development index (HDI), athletics events, and violence index. Multilevel analysis was conducted in HLM software. State-level characteristics explained ≈3% of the total variance in running performance. Of the total variance explained for the individual level, 56.4% was associated with male sex (β = −54.98; p < 0.001), age (β = 1.09; p < 0.001), body mass index (β = 6.86; p < 0.001), economic status (β = 6.23; p = 0.003), the perception of the natural environment (β = 7.58; p = 0.02), training frequency (β = −16.64; p < 0.001), and weekly volume (β = −0.30; p < 0.001). At the state level, only athletics events presented a positive and significant influence on performance. There is a significant role of the environment on the explanation of running performance variability, and given the diversity across states, environmental variables should not be neglected, as they are relevant to the exploration of other variables possibly related to running performance.
Pregnancy Outcome during the First COVID 19 Lockdown in Vienna, Austria
Authors: Kirchengast Sylvia , Hartmann Beda
Published: April 2021

The COVID 19 pandemic represents a major stress factor for non-infected pregnant women. Although maternal stress during pregnancy increases the risk of preterm birth and intrauterine growth restriction, an increasing number of studies yielded no negative effects of COVID 19 lockdowns on pregnancy outcome. The present study focused on pregnancy outcome during the first COVID 19 lockdown phase in Austria. In particular, it was hypothesized that the national lockdown had no negative effects on birth weight, low birth weight rate and preterm birth rate. In a retrospective medical record-based single center study, the outcome of 669 singleton live births in Vienna Austria during the lockdown phase between March and July 2020 was compared with the pregnancy outcome of 277 live births at the same hospital during the pre-lockdown months of January and February 2020 and, in addition, with the outcome of 28,807 live births between 2005 and 2019. The rate of very low gestational age was significantly lower during the lockdown phase than during the pre-lockdown phase. The rate of low gestational age, however, was slightly higher during the lockdown phase. Mean birth weight was significantly higher during the lockdown phase; the rates of low birth weight, very low birth weight and extremely low birth weight were significantly lower during the lockdown phase. In contrast, maternal gestational weight gain was significantly higher during the lockdown phase. The stressful lockdown phase in Austria seems to have no negative affect on gestational length and newborn weight among non-infected mothers.
The Effects of Urban Forms on the PM2.5 Concentration in China: A Hierarchical Multiscale Analysis
Authors: Jiang Mingyue , Wu Yizhen , Chang Zhijian , Shi Kaifang
Published: April 2021

For a better environment and sustainable development of China, it is indispensable to unravel how urban forms (UF) affect the fine particulate matter (PM2.5) concentration. However, research in this area have not been updated consider multiscale and spatial heterogeneities, thus providing insufficient or incomplete results and analyses. In this study, UF at different scales were extracted and calculated from remote sensing land-use/cover data, and panel data models were then applied to analyze the connections between UF and PM2.5 concentration at the city and provincial scales. Our comparison and evaluation results showed that the PM2.5 concentration could be affected by the UF designations, with the largest patch index (LPI) and landscape shape index (LSI) the most influential at the provincial and city scales, respectively. The number of patches (NP) has a strong negative influence (−0.033) on the PM2.5 concentration at the provincial scale, but it was not statistically significant at the city scale. No significant impact of urban compactness on the PM2.5 concentration was found at the city scale. In terms of the eastern and central provinces, LPI imposed a weighty positive influence on PM2.5 concentration, but it did not exert a significant effect in the western provinces. In the western cities, if the urban layout were either irregular or scattered, exposure to high PM2.5 pollution levels would increase. This study reveals distinct ties of the different UF and PM2.5 concentration at the various scales and helps to determine the reasonable UF in different locations, aimed at reducing the PM2.5 concentration.
DNA Methylation Patterns Correlate with the Expression of SCNN1A, SCNN1B, and SCNN1G (Epithelial Sodium Channel, ENaC) Genes
Authors: Pierandrei Silvia , Truglio Gessica , Ceci Fabrizio , Del Porto Paola , Bruno Sabina Maria , Castellani Stefano , Conese Massimo , Ascenzioni Fiorentina , Lucarelli Marco
Published: April 2021

The interplay between the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial sodium channel (ENaC) in respiratory epithelia has a crucial role in the pathogenesis of cystic fibrosis (CF). The comprehension of the mechanisms of transcriptional regulation of ENaC genes is pivotal to better detail the pathogenic mechanism and the genotype–phenotype relationship in CF, as well as to realize therapeutic approaches based on the transcriptional downregulation of ENaC genes. Since we aimed to study the epigenetic transcriptional control of ENaC genes, an assessment of their expression and DNA methylation patterns in different human cell lines, nasal brushing samples, and leucocytes was performed. The mRNA expression of CFTR and ENaC subunits α, β and γ (respectively SCNN1A, SCNN1B, and SCNN1G genes) was studied by real time PCR. DNA methylation of 5′-flanking region of SCNN1A, SCNN1B, and SCNN1G genes was studied by HpaII/PCR. The levels of expression and DNA methylation of ENaC genes in the different cell lines, brushing samples, and leukocytes were very variable. The DNA regions studied of each ENaC gene showed different methylation patterns. A general inverse correlation between expression and DNA methylation was evidenced. Leukocytes showed very low expression of all the 3 ENaC genes corresponding to a DNA methylated pattern. The SCNN1A gene resulted to be the most expressed in some cell lines that, accordingly, showed a completely demethylated pattern. Coherently, a heavy and moderate methylated pattern of, respectively, SCNN1B and SCNN1G genes corresponded to low levels of expression. As exceptions, we found that dexamethasone treatment appeared to stimulate the expression of all the 3 ENaC genes, without an evident modulation of the DNA methylation pattern, and that in nasal brushing a considerable expression of all the 3 ENaC genes were found despite an apparent methylated pattern. At least part of the expression modulation of ENaC genes seems to depend on the DNA methylation patterns of specific DNA regions. This points to epigenetics as a controlling mechanism of ENaC function and as a possible therapeutic approach for CF.
MicroRNA Regulation of Breast Cancer Stemness
Authors: Humphries Brock , Wang Zhishan , Yang Chengfeng
Published: April 2021

Recent advances in our understanding of breast cancer have demonstrated that cancer stem-like cells (CSCs, also known as tumor-initiating cell (TICs)) are central for progression and recurrence. CSCs are a small subpopulation of cells present in breast tumors that contribute to growth, metastasis, therapy resistance, and recurrence, leading to poor clinical outcome. Data have shown that cancer cells can gain characteristics of CSCs, or stemness, through alterations in key signaling pathways. The dysregulation of miRNA expression and signaling have been well-documented in cancer, and recent studies have shown that miRNAs are associated with breast cancer initiation, progression, and recurrence through regulating CSC characteristics. More specifically, miRNAs directly target central signaling nodes within pathways that can drive the formation, maintenance, and even inhibition of the CSC population. This review aims to summarize these research findings specifically in the context of breast cancer. This review also discusses miRNAs as biomarkers and promising clinical therapeutics, and presents a comprehensive summary of currently validated targets involved in CSC-specific signaling pathways in breast cancer.
Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model
Authors: Kedziora Sarah M. , Kräker Kristin , Markó Lajos , Binder Julia , Sugulle Meryam , Gauster Martin , Müller Dominik N. , Dechend Ralf , Haase Nadine , Herse Florian
Published: April 2021

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.
Anti-Angiogenic Therapy: Current Challenges and Future Perspectives
Authors: Lopes-Coelho Filipa , Martins Filipa , Pereira Sofia A. , Serpa Jacinta
Published: April 2021

Anti-angiogenic therapy is an old method to fight cancer that aims to abolish the nutrient and oxygen supply to the tumor cells through the decrease of the vascular network and the avoidance of new blood vessels formation. Most of the anti-angiogenic agents approved for cancer treatment rely on targeting vascular endothelial growth factor (VEGF) actions, as VEGF signaling is considered the main angiogenesis promotor. In addition to the control of angiogenesis, these drugs can potentiate immune therapy as VEGF also exhibits immunosuppressive functions. Despite the mechanistic rational that strongly supports the benefit of drugs to stop cancer progression, they revealed to be insufficient in most cases. We hypothesize that the rehabilitation of old drugs that interfere with mechanisms of angiogenesis related to tumor microenvironment might represent a promising strategy. In this review, we deepened research on the molecular mechanisms underlying anti-angiogenic strategies and their failure and went further into the alternative mechanisms that impact angiogenesis. We concluded that the combinatory targeting of alternative effectors of angiogenic pathways might be a putative solution for anti-angiogenic therapies.
Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside
Authors: Obrișcă Bogdan , Sorohan Bogdan , Tuță Liliana , Ismail Gener
Published: April 2021

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disorders caused by a loss of tolerance to endogenous nuclear antigens triggering an aberrant autoimmune response targeting various tissues. Lupus nephritis (LN), a major cause of morbidity and mortality in patients with SLE, affects up to 60% of patients. The recent insights into the genetic and molecular basis of SLE and LN paved the way for newer therapies to be developed for these patients. Apart from the traditional B-cell-centered view of this disease pathogenesis, acknowledging that multiple extrarenal and intrarenal pathways contribute to kidney-specific autoimmunity and injury may help refine the individual therapeutic and prognostic characterization of such patients. Accordingly, the formerly induction-maintenance treatment strategy was recently challenged with the exciting results obtained from the trials that evaluated add-on therapy with voclosporin, belimumab, or Obinutuzumab. The scope of this review is to provide an insight into the current knowledge of LN pathogenesis and future therapeutic strategies.
Molecular Characterization of Heat-Induced HSP11.0 and Master-Regulator HSF from Cotesia chilonis and Their Consistent Response to Heat Stress
Authors: He Fu-Jing , Zhu Feng , Lu Ming-Xing , Du Yu-Zhou
Published: April 2021

Small heat shock proteins (sHSPs) are members of the heat shock protein (HSP) family that play an important role in temperature stress, and heat shock factors (HSFs) are transcriptional activators that regulate HSP expression. Cotesia chilonis, the major endoparasitoid of Chilo suppressalis, modulates the C. suppressalis population in the field. In this study, we cloned and characterized two genes from C.chilonis: the heat-induced HSP11.0 gene (Cchsp11.0) that consisted of a 306-bp ORF, and the master regulator HSF (Cchsf) containing an 1875-bp ORF. CcHSP11.0 contained a chaperonin cpn10 signature motif that is conserved in other hymenopteran insects. CcHSF is a typical HSF and contains a DNA-binding domain, two hydrophobic heptad repeat domains, and a C-terminal trans-activation domain. Neither Cchsp11.0 or Cchsf contain introns. Real-time quantitative PCR revealed that Cchsp11.0 and Cchsf were highly induced at 36 °C and 6 °C after a 2-h exposure. Overall, the induction of Cchsf was lower than Cchsp11.0 at low temperatures, whereas the opposite was true at high temperatures. In conclusion, both Cchsp11.0 and Cchsf are sensitive to high and low temperature stress, and the expression pattern of the two genes were positively correlated during temperature stress.
Developing New Agents for Treatment of Childhood Cancer: Challenges and Opportunities for Preclinical Testing
Authors: Ghilu Samson , Kurmasheva Raushan T. , Houghton Peter J.
Published: April 2021

Developing new therapeutics for the treatment of childhood cancer has challenges not usually associated with adult malignancies. Firstly, childhood cancer is rare, with approximately 12,500 new diagnoses annually in the U.S. in children 18 years or younger. With current multimodality treatments, the 5-year event-free survival exceeds 80%, and 70% of patients achieve long-term “cure”, hence the overall number of patients eligible for experimental drugs is small. Childhood cancer comprises many disease entities, the most frequent being acute lymphoblastic leukemias (25% of cancers) and brain tumors (21%), and each of these comprises multiple molecular subtypes. Hence, the numbers of diagnoses even for the more frequently occurring cancers of childhood are small, and undertaking clinical trials remains a significant challenge. Consequently, development of preclinical models that accurately represent each molecular entity can be valuable in identifying those agents or combinations that warrant clinical evaluation. Further, new regulations under the Research to Accelerate Cures and Equity for Children Act (RACE For Children Act) will change the way in which drugs are developed. Here, we will consider some of the limitations of preclinical models and consider approaches that may improve their ability to translate therapy to clinical trial more accurately.
Factors Influencing Contrast Sensitivity Function in Eyes with Mild Cataract
Authors: Kamiya Kazutaka , Fujimura Fusako , Kawamorita Takushi , Ando Wakako , Iida Yoshihiko , Shoji Nobuyuki
Published: April 2021

This study was aimed to evaluate the relationship between the area under the log contrast sensitivity function (AULCSF) and several optical factors in eyes suffering mild cataract. We enrolled 71 eyes of 71 patients (mean age, 71.4 ± 10.7 (standard deviation) years) with cataract formation who were under surgical consultation. We determined the area under the log contrast sensitivity function (AULCSF) using a contrast sensitivity unit (VCTS-6500, Vistech). We utilized single and multiple regression analyses to investigate the relevant factors in such eyes. The mean AULSCF was 1.06 ± 0.16 (0.62 to 1.38). Explanatory variables relevant to the AULCSF were, in order of influence, logMAR best spectacle-corrected visual acuity (BSCVA) (p < 0.001, partial regression coefficient B = −0.372), and log(s) (p = 0.023, B = −0.032) (adjusted R2 = 0.402). We found no significant association with other variables such as age, gender, uncorrected visual acuity, nuclear sclerosis grade, or ocular HOAs. Eyes with better BSCVA and lower log(s) are more susceptible to show higher AULCSF, even in mild cataract subjects. It is indicated that both visual acuity and intraocular forward scattering play a role in the CS function in such eyes.
Translating Virtual Reality Cue Exposure Therapy for Binge Eating into a Real-World Setting: An Uncontrolled Pilot Study
Authors: Nameth Katherine , Brown Theresa , Bullock Kim , Adler Sarah , Riva Giuseppe , Safer Debra , Runfola Cristin
Published: April 2021

Binge-eating disorder (BED) and bulimia nervosa (BN) have adverse psychological and medical consequences. Innovative interventions, like the integration of virtual reality (VR) with cue-exposure therapy (VR-CET), enhance outcomes for refractory patients compared to cognitive behavior therapy (CBT). Little is known about the feasibility and acceptability of translating VR-CET into real-world settings. To investigate this question, adults previously treated for BED or BN with at least one objective or subjective binge episode/week were recruited from an outpatient university eating disorder clinic to receive up to eight weekly one-hour VR-CET sessions. Eleven of 16 (68.8%) eligible patients were enrolled; nine (82%) completed treatment; and 82% (9/11) provided follow-up data 7.1 (SD = 2.12) months post-treatment. Overall, participant and therapist acceptability of VR-CET was high. Intent-to-treat objective binge episodes (OBEs) decreased significantly from 3.3 to 0.9/week (p < 0.001). Post-treatment OBE 7-day abstinence rate for completers was 56%, with 22% abstinent for 28 days at follow-up. Among participants purging at baseline, episodes decreased from a mean of one to zero/week, with 100% abstinence maintained at follow-up. The adoption of VR-CET into real-world clinic settings appears feasible and acceptable, with a preliminary signal of effectiveness. Findings, including some loss of treatment gains during follow-up may inform future treatment development.
The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology: A Retrospective Review
Authors: Layfield Lester J.
Published: April 2021

Since the introduction of the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology, much experience has been gained and published concerning the utility of the diagnostic categories, malignancy risk of the categories and reproducibility of the system. This new information has resulted in modifications to the system which will become part of the World Health Organization (WHO) System for Reporting Pancreatic Cytology. Herein we report our experience with the system and information from the published literature.
What Is the Optimal Duration of Adjuvant Mitotane Therapy in Adrenocortical Carcinoma? An Unanswered Question
Authors: Basile Vittoria , Puglisi Soraya , Altieri Barbara , Canu Letizia , Libè Rossella , Ceccato Filippo , Beuschlein Felix , Quinkler Marcus , Calabrese Anna , Perotti Paola , Berchialla Paola , Dischinger Ulrich , Megerle Felix , Baudin Eric , Bourdeau Isabelle , Lacroix André , Loli Paola , Berruti Alfredo , Kastelan Darko , Haak Harm R. , Fassnacht Martin , Terzolo Massimo
Published: April 2021

A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence.
A Pocket-Textured Surface for Improving the Tribological Properties of Point Contact under Starved Lubrication
Authors: Wang Wei , Zhao Wenhan , Liu Yang , Zhang Hui , Hua Meng , Dong Guangneng , Tam Hon-Yuen , Chin Kwai-Sang
Published: April 2021

This paper reports a novel pocket-textured surface for improving the tribological properties of point contact under starved lubrication by possibly storing and releasing oil, and homogenizing the surface contact pressure. The ball-on-disk experimental results confirmed the coefficient of friction (COF) and wear reduction effect of such pocket-texturing. The maximum reduction rate was 40% compared with a flat surface under the same operating conditions. Analyses on experimental results attributed the oil storage effect and enhanced the secondary lubrication effect within the starved lubrication state, to become the main mechanism. In addition, the plate elasticity and the Hertzian contact principles were employed to estimate the pressure and the load acting on the surface. The experimental results and numerical analysis substantiated the design of pocket-textured surface, making it likely to enlarge about 50% of contact surface and to reduce 90% of equivalent stress in comparison to those of conventional surfaces.
Seasonal Variation of the Proximate Composition, Mineral Content, Fatty Acid Profiles and Other Phytochemical Constituents of Selected Brown Macroalgae
Authors: Garcia-Vaquero Marco , Rajauria Gaurav , Miranda Marta , Sweeney Torres , Lopez-Alonso Marta , O’Doherty John
Published: April 2021

The main objective was to determine the chemical, phytochemical, fatty acid and mineral profiles of three commercially relevant brown macroalgae (Laminaria digitata, Laminaria hyperborea and Ascophyllum nodosum) collected each season for two years off the west coast of Ireland. All the chemical, phytochemical, fatty acid and minerals analysed varied significantly depending on the macroalgal species, season and year of collection. Overall, the protein contents of macroalgae were negatively correlated with carbohydrate content. Protein (2–11%) was at its highest during winter and/or spring, decreasing to a minimum during summer and/or autumn. The three macroalgal species analysed in this study had clearly differentiated fatty acid profiles. The concentration of fatty acids was higher in A. nodosum compared with both Laminaria species. The mineral profile of the three macroalgal species was rich in essential metals, particularly Ca, Mg and P, while the levels of I were approximately 9- to 10-fold higher in both Laminaria spp. compared with A. nodosum. The levels of toxic metals (Cd, Hg and Pb) in all the macroalgal species studied were low in the current study; while the levels of total As were high (49–64 mg/kg DW macroalgae) compared with previous reports.
Nanocomposite Anion Exchange Membranes with a Conductive Semi-Interpenetrating Silica Network
Authors: Sgreccia Emanuela , Di Vona Maria , Antonaroli Simonetta , Ercolani Gianfranco , Sette Marco , Pasquini Luca , Knauth Philippe
Published: April 2021

Nanocomposite anion exchange membranes were synthesized based on poly(sulfone trimethylammonium) chloride. A hybrid semi-interpenetrating silica network containing a large amount of quaternary ammonium groups was prepared by two sol–gel routes, in situ with a single precursor, N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (TMSP), or ex situ mixing two precursors, TMSP and 3-(2-aminoethylamino)propyldimethoxy-methylsilane (AEAPS). The properties of these hybrid composites and their degradation after immersion in 1 M KOH at 60 °C were studied. The degradation is reduced in the composite materials with a lower decrease in the ion exchange capacity. FTIR spectra showed that a main degradation mechanism with a single precursor TMSP is the dissolution of the hybrid silica network in KOH, whereas it is stable with the mixture of TMSP/AEASP. This conclusion is in agreement with the thermogravimetric analysis. The mechanical properties show a better ductility with a single precursor and higher stiffness and strength, but less ductility, by the ex situ route. The activation energy was between 0.25 and 0.14 eV for Cl and OH ion conduction, respectively, consistent with the migration mechanism.
Effect of Alloying Additives and Microadditives on Hardenability Increase Caused by Action of Boron
Authors: Białobrzeska Beata
Published: April 2021

The presented work was aimed at evaluating influence of boron on hardenability of steel quantitatively and evaluating this effect during complex use of boron with other alloying additives like chromium, vanadium and titanium. For this purpose, eight melts with variable chemical compositions were prepared. From the ingots, cylindrical specimens with normalized dimensions according to EN ISO 642:1999 were cut out and subjected to full annealing at 1200 °C and to normalizing at 900 °C. Such specimens were subjected to the hardenability Jominy test. In order to distinguish the influence of boron on hardenability of a given melt and thus to eliminate the differences resulting from its chemical composition, grain size and austenitizing temperature, the obtained ideal critical diameter was corrected and the boron effectiveness factor was determined. The performed examinations and analyses showed that inadequate quantities of microadditives result in losing the benefits coming from introduction of boron as the hardenability-improving element and can even result in a reduction of hardenability of the boron-containing steel.
Fabrication of Roughened Electrodeposited Copper Coating on Steel for Dissimilar Joining of Steel and Thermoplastic Resin
Authors: Arai Susumu , Iwashita Ryosuke , Shimizu Masahiro , Inoue Junki , Horita Masaomi , Nagaoka Takashi , Itabashi Masami
Published: April 2021

Electrodeposition of a roughened copper coating onto steel was carried out to produce a bonding surface for thermoplastic resin (polyphenylenesulfide). The roughened copper film was electrodeposited using a copper sulfate bath containing polyacrylic acid (PAA). Following injection molding of the resin, the bonding strength was evaluated in a tensile lap shear strength test, followed by durability testing at high temperature and humidity (85 ± 2 °C and 85 ± 2% relative humidity, respectively) for 2000 h, and a thermal shock test (−50 °C–150 °C) for 1000 cycles. An analysis of the boundary microstructure showed that the PAA concentration had a large effect on the surface morphology of the copper film. The shear strength of the joint between the coated steel substrate and the resin was more than 40 MPa, and the bonding strength also remained above 40 MPa throughout the durability test. During the thermal shock test, although the bonding strength gradually decreased with increasing number of cycles, it remained at over 20 MPa, even after 1000 cycles. This method achieves not only high initial bonding strength, but also durability for joints between dissimilar materials such as steel and resin.
Recovery of Gold from Ore with Potassium Ferrocyanide Solution under UV Light
Authors: Liu Ziyuan , Kou Jue , Xing Yi , Sun Chunbao
Published: April 2021

In this study, potassium ferrocyanide, a nontoxic cyanide precursor in dark and diffuse reflection environment, was applied as reagent for the leaching of gold. The free cyanide ions could gradually release from potassium ferrocyanide solution under the ultraviolet light. Orthogonal leaching experiments were performed in gold ore to analyze the effect of solution pH, potassium ferrocyanide dosage, and temperature in a potassium ferrocyanide solution system under UV light. Response surface methodology (RSM) was applied to explore the role of potassium ferrocyanide in gold leaching; optimized results showed that the gold recovery reached 67.74% in a high-alkaline environment at a 12.6 pH, 3.8 kg/t potassium ferrocyanide dosage, 62 °C, and irradiance of 10 mW·cm−2. The gold leaching kinetics were monitored by quartz crystal microbalance with dissipation (QCM-D) of potassium ferrocyanide solution. The results indicate that the gold extraction process could be divided into two stages: adsorption and leaching, and a rigid adsorption layer formed on the reaction surface. Furthermore, X-ray photoelectron spectroscopy (XPS) analysis of the gold sensor surface after leaching reaction showed that –C≡N appears on the gold sensor surface, and the gold is oxidized to form AuCN complexes.
Modulation of Renal Function in a Metabolic Syndrome Rat Model by Antioxidants in Hibiscus sabdariffa L.
Authors: Rodríguez-Fierros Félix Leao , Guarner-Lans Verónica , Soto María Elena , Manzano-Pech Linaloe , Díaz-Díaz Eulises , Soria-Castro Elizabeth , Rubio-Ruiz María Esther , Jiménez-Trejo Francisco , Pérez-Torres Israel
Published: April 2021

Metabolic syndrome (MS) is the association of three or more pathologies among which obesity, hypertension, insulin resistance, dyslipidemia, and diabetes are included. It causes oxidative stress (OS) and renal dysfunction. Hibiscus sabdariffa L. (HSL) is a source of natural antioxidants that may control the renal damage caused by the MS. The objective of this work was to evaluate the effect of a 2% HSL infusion on renal function in a MS rat model induced by the administration of 30% sucrose in drinking water. 24 male Wistar rats were divided into 3 groups: Control rats, MS rats and MS + HSL rats. MS rats had increased body weight, systolic blood pressure, triglycerides, insulin, HOMA index, and leptin (p ≤ 0.04). Renal function was impaired by an increase in perfusion pressure in the isolated and perfused kidney, albuminuria (p ≤ 0.03), and by a decrease in clearance of creatinine (p ≤ 0.04). The activity of some antioxidant enzymes including the superoxide dismutase isoforms, peroxidases, glutathione peroxidase, glutathione-S-transferase was decreased (p ≤ 0.05). Lipoperoxidation and carbonylation were increased (p ≤ 0.001). The nitrates/nitrites ratio, total antioxidant capacity, glutathione levels and vitamin C were decreased (p ≤ 0.03). The treatment with 2% HSL reversed these alterations. The results suggest that the treatment with 2% HSL infusion protects renal function through its natural antioxidants which favor an improved renal vascular response. The infusion contributes to the increase in the glomerular filtration rate, by promoting an increase in the enzymatic and non-enzymatic antioxidant systems leading to a decrease in OS and reestablishing the normal renal function.
Bioactivity-Guided Isolation of Phytochemicals from Vaccinium dunalianum Wight and Their Antioxidant and Enzyme Inhibitory Activities
Authors: Zhao Tianrui , Sun Mengxue , Kong Lingpeng , Xue Qingwang , Wang Yudan , Wang Yifen , Khan Afsar , Cao Jianxin , Cheng Guiguang
Published: April 2021

Vaccinium dunalianum Wight, usually processed as a traditional folk tea beverage, is widely distributed in the southwest of China. The present study aimed to investigate the antioxidant, α-glucosidase and pancreatic lipase inhibitory activities of V.dunalianum extract and isolate the bioactive components. In this study, the crude extract (CE) from the buds of V. dunalianum was prepared by the ultrasound-assisted extraction method in 70% methanol and then purified with macroporous resin D101 to obtain the purified extract (PM). Five fractions (Fr. A–E) were further obtained by MPLC column (RP-C18). Bioactivity assays revealed that Fr. B with 40% methanol and Fr. D with 80% methanol had better antioxidant with 0.48 ± 0.03 and 0.62 ± 0.01 nM Trolox equivalent (TE)/mg extract for DPPH, 0.87 ± 0.02 and 1.58 ± 0.02 nM TE/mg extract for FRAP, 14.42 ± 0.41 and 19.25 ± 0.23 nM TE/mg extract for ABTS, and enzyme inhibitory effects with IC50 values of 95.21 ± 2.21 and 74.55 ± 3.85 for α-glucosidase, and 142.53 ± 11.45 and 128.76 ± 13.85 µg/mL for pancreatic lipase. Multivariate analysis indicated that the TPC and TFC were positively related to the antioxidant activities. Further phytochemical purification led to the isolation of ten compounds (1–10). 6-O-Caffeoylarbutin (7) showed significant inhibitory effects on α-glucosidase and pancreatic lipase enzymes with values of 38.38 ± 1.84 and 97.56 ± 7.53 µg/mL, and had the highest antioxidant capacity compared to the other compounds.
Increase in Autoantibodies-Abzymes with Peroxidase and Oxidoreductase Activities in Experimental Autoimmune Encephalomyelitis Mice during the Development of EAE Pathology
Authors: Tolmacheva Anna S. , Aulova Kseniya S. , Urusov Andrey E. , Orlovskaya Irina A. , Nevinsky Georgy A.
Published: April 2021

The exact mechanisms of multiple sclerosis (MS) development are still unknown, but the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice is associated with the violation of bone marrow hematopoietic stem cells (HSCs) differentiation profiles associated with the production of harmful for human’s autoantibodies hydrolyzing myelin basic protein, myelin oligodendrocyte glycoprotein (MOG35–55), and DNA. It was shown that IgGs from the sera of healthy humans and autoimmune patients oxidize many different compounds due to their H2O2-dependent peroxidase and oxidoreductase activity in the absence of H2O2. Here we first analyzed the change in the relative redox activities of IgGs antibodies from the blood of C57BL/6 mice over time at different stages of the EAE development. It was shown that the peroxidase activity of mice IgGs in the oxidation of ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) is on average 6.9-fold higher than the oxidoreductase activity. The peroxidase activity of IgGs increased during the spontaneous development of EAE during 40 days, 1.4-fold. After EAE development acceleration due to mice immunization with MOG35–55 (5.3-fold), complexes of bovine DNA with methylated bovine serum albumin (DNA-metBSA; 3.5-fold), or with histones (2.6-fold), the activity was increased much faster. The increase in peroxidase activity after mice immunization with MOG35–55 and DNA-metBSA up to 40 days of experiments was relatively gradual, while for DNA-histones complex was observed its sharp increase at the acute phase of EAE (14–20 days). All data show that IgGs’ redox activities can play an important role in the protection of mice from toxic compounds and oxidative stress.
Advances in Nanotoxicology: Towards Enhanced Environmental and Physiological Relevance and Molecular Mechanisms
Authors: Kahru Anne , Mortimer Monika
Published: April 2021

Nanotoxicology, a discipline transpired by the need to assess the human and environmental safety of nanoscale materials, has evolved over the past 15 years into a mature area of toxicology [...]
Synchrotron Radiation Spectroscopy and Transmission Electron Microscopy Techniques to Evaluate TiO2 NPs Incorporation, Speciation, and Impact on Root Cells Ultrastructure of Pisum sativum L. Plants
Authors: Muccifora Simonetta , Castillo-Michel Hiram , Barbieri Francesco , Bellani Lorenza , Ruffini Castiglione Monica , Spanò Carmelina , Pradas del Real Ana E. , Giorgetti Lucia , Tassi Eliana L.
Published: April 2021

Biosolids (Bs) for use in agriculture are an important way for introducing and transferring TiO2 nanoparticles (NPs) to plants and food chain. Roots of Pisum sativum L. plants grown in Bs-amended soils spiked with TiO2 800 mg/kg as rutile NPs, anatase NPs, mixture of both NPs and submicron particles (SMPs) were investigated by Transmission Electron Microscopy (TEM), synchrotron radiation based micro X-ray Fluorescence and micro X-ray Absorption Near-Edge Structure (µXRF/µXANES) and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). TEM analysis showed damages in cells ultrastructure of all treated samples, although a more evident effect was observed with single anatase or rutile NPs treatments. Micro-XRF and TEM evidenced the presence of nano and SMPs mainly in the cortex cells near the rhizodermis. Micro-XRF/micro-XANES analysis revealed anatase, rutile, and ilmenite as the main TiO2 polymorphs in the original soil and Bs, and the preferential anatase uptake by the roots. For all treatments Ti concentration in the roots increased by 38–56%, however plants translocation factor (TF) increased mostly with NPs treatment (261–315%) and less with SMPs (about 85%), with respect to control. In addition, all samples showed a limited transfer of TiO2 to the shoots (very low TF value). These findings evidenced a potential toxicity of TiO2 NPs present in Bs and accumulating in soil, suggesting the necessity of appropriate regulations for the occurrence of NPs in Bs used in agriculture.