bluuebunny/crossref_metadata_2025 huggingface dataset:
Mental Health and the Symptoms of PTSD in People with Depression and Anxiety Disorders during the COVID-19 Pandemic
Authors: Golińska Paulina Beata , Cieślak Mariusz , Hubert Olimpia , Bidzan Mariola
Published: May 2021

The purpose of this study was to examine the severity of post-traumatic stress disorder (PTSD) symptoms related to the COVID-19 pandemic in people with no diagnosis of mental illness, as well as in people who were diagnosed with depression or anxiety. Moreover, this study aimed to investigate the interplay between PTSD symptoms and self-assessed mental health associated with well-being. The 210 participants were divided into 3 groups: mentally healthy, participants with diagnosed depression, and participants with anxiety disorders. To evaluate the subjective well-being of the participants, the Polish adaptation of the Mental Health Continuum–Short Form (MHC–SF) was applied. The Impact Event Scale-Revised (IES-R) was used to measure the severity of PTSD symptoms. At least a moderate worsening of PTSD symptoms was observed in participants of all groups. The results were as follows: healthy participants M = 37.35 (SD = 18.46); participants with depression M = 36.05 (SD = 18.02); participants with anxiety M = 44.52 (SD = 18.08). The participants diagnosed with depression showed the lowest level of mental well-being M = 41.58 (SD = 15.02). Conclusion: People diagnosed with depression had both the lowest level of well-being and the lowest severity of symptoms specific to PTSD. In all three groups, lower emotional well-being was linked to greater PTSD symptoms.
The Effect of a Physical Activity Coaching Intervention on Accelerometer-Measured Sedentary Behaviours in Insufficiently Physically Active Ambulatory Hospital Patients
Authors: Barrett Stephen , Begg Stephen , O′Halloran Paul , Kingsley Michael
Published: May 2021

Little is known about the impact that physical activity (PA) coaching interventions have on sedentary behaviours. The aim of this study was to investigate if a coaching intervention that increases PA coincidentally influences objectively measured sedentary time in insufficiently physically active adults. We recruited 120 insufficiently physically active ambulatory hospital patients and randomized them to either receive a PA coaching intervention designed to increase objectively measured moderate-to-vigorous-intensity PA (MVPA) or be part of a control group. Participants wore an accelerometer for seven days at baseline, post-intervention (three months) and follow-up (nine months). Changes in the average length of sedentary bouts, proportion of time in sedentary behaviours and number of sedentary bouts were evaluated using mixed-model ANOVAs. At baseline, both groups undertook 67 ± 13 sedentary bouts and spent 69% ± 6% of their time in sedentary behaviours. Compared with control, the intervention group decreased the number of sedentary bouts by 24% and the proportion of time in sedentary behaviours by 7% (p < 0.001). Significant changes were not observed between the groups for average length of sedentary bouts. The PA intervention led to a decrease in the number of sedentary bouts and proportion of time in sedentary behaviours. Future research should investigate PA coaching interventions designed to target simultaneous changes in MVPA and sedentary behaviours.
Are Core Stability Tests Related to Single Leg Squat Performance in Active Females?
Authors: Guillén-Rogel Paloma , Barbado David , Franco-Escudero Cristina , San Emeterio Cristina , Marín Pedro J.
Published: May 2021

Core stability (CS) deficits can have a significant impact on lower limb function. The aim of this study was to investigate the relationship between two dynamic core exercise assessments and dynamic knee valgus during single-leg squats. In total, 20 physically active female students participated in this study. The OCTOcore smartphone application assesses CS during two dynamic exercise tests, the partial range single-leg deadlift (SLD) test and the bird-dog (BD) test. A two-dimensional assessment of a single-leg squat test was used to quantify participants’ hip frontal angle (HFASLS) and knee frontal plane projection angle (FPPASLS). Ankle dorsiflexion was evaluated through the weight-bearing dorsiflexion test. The correlational analyses indicated that the HFASLS was significantly related to the partial range single-leg deadlift test (r = 0.314, p < 0.05) and ankle dorsiflexion (r = 0.322, p < 0.05). The results showed a significant difference (p < 0.05) in the CS test between cases categorised as dynamic knee valgus (>10°) and normal (≤10°). The CS deficit may influence the neuromuscular control of the lumbopelvic-hip complex during single-leg movements. The link between CS and kinematic factors related to knee injuries was only observed when CS was measured in the SLD test but not in the BD test.
Cognitive Neural Mechanism of Social Anxiety Disorder: A Meta-Analysis Based on fMRI Studies
Authors: Yu Xianglian , Ruan Yijun , Zhang Yawen , Wang Jiayi , Liu Yuting , Zhang Jibiao , Zhang Lin
Published: May 2021

Objective: The present meta-analysis aimed to explore the cognitive and neural mechanism of social anxiety disorder (SAD) from a whole-brain view, and compare the differences in brain activations under different task paradigms. Methods: We searched Web of Science Core Collection and other databases with the keywords related to social anxiety, social phobia, and functional magnetic resonance imaging (fMRI) for comparing persons with SAD to healthy controls and used the activation likelihood estimation method. Thirty-seven papers met the inclusion criteria, including 15 with emotional faces as stimuli, 8 presenting specific situations as stimuli, and 14 using other types of tasks as stimuli. Among these papers, 654 participants were in the SAD group and 594 participants were in the control group with 335 activation increase points and 115 activation decrease points. Results: Whole-brain analysis showed that compared with healthy controls, persons with SAD showed significantly lower activation of the left anterior cingulate gyrus (MNI coordinate: x = −6, y = 22, z = 38; p 0.001). Sub-group analysis based on task indicated that when performing tasks with emotional faces as stimuli, persons with SAD showed significantly lower activation of the left cerebellar slope and fusiform gyrus (MNI coordinate: x = −26, y = −68, z = −12; p 0.001), and significantly higher activation of the right supramarginal gyrus and angular gyrus, than healthy controls (MNI coordinate: x = 58, y = −52, z = 30; p 0.001). Conclusion: Individuals with social anxiety disorder show abnormal activation in the cingulate gyrus, which is responsible for the process of attention control, and task type can influence the activation pattern.
Different Patterns in Ranking of Risk Factors for the Onset Age of Acute Myocardial Infarction between Urban and Rural Areas in Eastern Taiwan
Authors: Huang Hsiu-Ju , Lee Chih-Wei , Li Tse-Hsi , Hsieh Tsung-Cheng
Published: May 2021

This cross-sectional study aimed to investigate the difference in ranking of risk factors of onset age of acute myocardial infarction (AMI) between urban and rural areas in Eastern Taiwan. Data from 2013 initial onset of AMI patients living in the urban areas (n = 1060) and rural areas (n = 953) from January 2000 to December 2015, including onset age, and conventional risk factors including sex, smoking, diabetes, hypertension, dyslipidemia, and body mass index (BMI). The results of multiple linear regressions analysis showed smoking, obesity, and dyslipidemia were early-onset reversible risk factors of AMI in both areas. The ranking of impacts of them on the age from high to low was obesity (β = −6.7), smoking (β = −6.1), and dyslipidemia (β = −4.8) in the urban areas, while it was smoking (β = −8.5), obesity (β= −7.8), and dyslipidemia (β = −5.1) in the rural areas. Furthermore, the average onset ages for the patients who smoke, are obese, and have dyslipidemia simultaneously was significantly earlier than for patients with none of these comorbidities in both urban (13.6 years) and rural (14.9 years) areas. The findings of this study suggest that the different prevention strategies for AMI should be implemented in urban and rural areas.
Human Biomonitoring Data Enables Evidence-Informed Policy to Reduce Internal Exposure to Persistent Organic Compounds: A Case Study
Authors: Colles Ann , Coertjens Dries , Morrens Bert , Den Hond Elly , Paulussen Melissa , Bruckers Liesbeth , Govarts Eva , Covaci Adrian , Koppen Gudrun , Croes Kim , Nelen Vera , Van Larebeke Nicolas , De Henauw Stefaan , Fierens Tine , Van Gestel Griet , Chovanova Hana , Mampaey Maja , Van Campenhout Karen , Loots Ilse , Baeyens Willy , Schoeters Greet
Published: May 2021

Human biomonitoring (HBM) monitors levels of environmental pollutants in human samples, which often is a topic of concern for residents near industrially contaminated sites (ICSs). Around an ICS area in Menen (Belgium), including a (former) municipal waste incinerator and a metal recovery plant, increasing environmental concentrations of dioxins and polychlorinated biphenyls (PCBs) were observed, causing growing concern among residents and authorities. The local community succeeded in convincing the responsible authorities to investigate the problem and offer research funding. Persistent organic pollutants (POPs) were measured in two consecutive HBM studies (2002–2006 and 2010–2011), in the context of the Flemish Environment and Health Study (FLEHS), as well as in soil and locally produced food. Meanwhile, local authorities discouraged consumption of locally produced food in a delineated area of higher exposure risk. Ultimately, HBM and environmental data enabled tailored dietary recommendations. This article demonstrates the usefulness of HBM in documenting the body burdens of residents near the ICS, identifying exposure routes, evaluating remediating actions and providing information for tailored policy strategies aiding to further exposure reduction. It also highlights the role of the local stakeholders as an example of community-based participatory research and how such an approach can create societal support for research and policy.
Tobacco Harm Reduction as a Path to Restore Trust in Tobacco Control
Authors: Antin Tamar M. J. , Hunt Geoffrey , Annechino Rachelle
Published: May 2021

The controversy of tobacco harm reduction in the United States persists despite evidence that an important audience of tobacco prevention and control, i.e., the people who use or are likely to use nicotine and tobacco products, are engaging in practices that may be considered harm reduction. Despite this, a significant proportion of the US tobacco control and prevention field continues to be guided by a precept that there is “no safe tobacco,” therefore failing to acknowledge practices that may be used to reduce the harms associated with consuming combustible forms of nicotine and tobacco. In this commentary, we argue that ignoring the potential benefits of harm reduction strategies may unintentionally lead to an erosion of trust in tobacco control among some members of the public. Trust in tobacco control as an institution is crucial for the success of tobacco control efforts. To ensure trust, we must return to our basic principles of doing no harm, developing programs that are responsive to people’s experiences, and providing resources in assisting people to reduce the harms that may be associated with practices, such as smoking, which adversely affect health. Only by respecting an individual’s priorities can we cultivate trust and develop tobacco prevention efforts that are grounded in the realities of people’s lives and responsive to their needs.
Health Care Resources and 24,910 Deaths Due to Traffic Accidents: An Ecological Mortality Study in Poland
Authors: Genowska Agnieszka , Jamiołkowski Jacek , Szafraniec Krystyna , Fryc Justyna , Pająk Andrzej
Published: May 2021

Background: Deaths due to traffic accidents are preventable and the access to health care is an important determinant of traffic accident case fatality. This study aimed to assess the relation between mortality due to traffic accidents and health care resources (HCR), at the population level, in 66 sub-regions of Poland. Methods: An area-based HCR index was delivered from the rates of physicians, nurses, and hospital beds. Associations between mortality from traffic accidents and the HCR index were tested using multivariate Poisson regression models. Results: In the sub-regions studied, the average mortality from traffic accidents was 11.7 in 2010 and 9.3/100.000 in 2015. After adjusting for sex, age and over time trends in mortality, out-of-hospital deaths were more frequently compared to hospitalized fatal cases (incidence rate ratio (IRR) = 1.68, 95% CI 1.45–1.93). Compared to sub-regions with high HCR, mortality from traffic accidents was higher in sub-regions with low and moderate HCR (IRR = 1.25, 95% CI 1.11–1.42 and IRR = 1.19, 95% CI 1.02–1.38, respectively), which reflected the differences in out-of-hospital mortality most pronounced in car accidents. Conclusions: Poor HCR is an important factor that explains the territorial differentiation of mortality due to traffic accidents in Poland. The high percentage of out-of-hospital deaths indicates the importance of preventive measures and the need for improvement in access to health care to reduce mortality due to traffic accidents.
Impacts of Autonomous Vehicles on Greenhouse Gas Emissions—Positive or Negative?
Authors: Massar Moneim , Reza Imran , Rahman Syed Masiur , Abdullah Sheikh Muhammad Habib , Jamal Arshad , Al-Ismail Fahad Saleh
Published: May 2021

The potential effects of autonomous vehicles (AVs) on greenhouse gas (GHG) emissions are uncertain, although numerous studies have been conducted to evaluate the impact. This paper aims to synthesize and review all the literature regarding the topic in a systematic manner to eliminate the bias and provide an overall insight, while incorporating some statistical analysis to provide an interval estimate of these studies. This paper addressed the effect of the positive and negative impacts reported in the literature in two categories of AVs: partial automation and full automation. The positive impacts represented in AVs’ possibility to reduce GHG emission can be attributed to some factors, including eco-driving, eco traffic signal, platooning, and less hunting for parking. The increase in vehicle mile travel (VMT) due to (i) modal shift to AVs by captive passengers, including elderly and disabled people and (ii) easier travel compared to other modes will contribute to raising the GHG emissions. The result shows that eco-driving and platooning have the most significant contribution to reducing GHG emissions by 35%. On the other side, easier travel and faster travel significantly contribute to the increase of GHG emissions by 41.24%. Study findings reveal that the positive emission changes may not be realized at a lower AV penetration rate, where the maximum emission reduction might take place within 60–80% of AV penetration into the network.
Vasculitis, Autoimmunity, and Cytokines: How the Immune System Can Harm the Brain
Authors: Tesser Alessandra , Pin Alessia , Mencaroni Elisabetta , Gulino Virginia , Tommasini Alberto
Published: May 2021

More and more findings suggest that neurological disorders could have an immunopathological cause. Thus, immune-targeted therapies are increasingly proposed in neurology (even if often controversial), as anakinra, inhibiting IL-1 for febrile inflammatory illnesses, and JAK inhibitors for anti-interferons treatment. Precision medicine in neurology could be fostered by a better understanding of the disease machinery, to develop a rational use of immuno-modulators in clinical trials. In this review, we focus on monogenic disorders with neurological hyper-inflammation/autoimmunity as simplified “models” to correlate immune pathology and targeted treatments. The study of monogenic models yields great advantages for the elucidation of the pathogenic mechanisms that can be reproduced in cellular/animal models, overcoming the limitations of biological samples to study. Moreover, monogenic disorders provide a unique tool to study the mechanisms of neuroinflammatory and autoimmune brain damage, in all their manifestations. The insight of clinical, pathological, and therapeutic aspects of the considered monogenic models can impact knowledge about brain inflammation and can provide useful hints to better understand and cure some neurologic multifactorial disorders.
Classroom Movement Breaks Reduce Sedentary Behavior and Increase Concentration, Alertness and Enjoyment during University Classes: A Mixed-Methods Feasibility Study
Authors: Peiris Casey L. , O’Donoghue Gráinne , Rippon Lewis , Meyers Dominic , Hahne Andrew , De Noronha Marcos , Lynch Julia , Hanson Lisa C.
Published: May 2021

This mixed-methods study aimed to determine the feasibility of incorporating movement breaks into university classes in terms of acceptability (disruption, engagement, satisfaction), practicality (ease of scheduling and conducting breaks) and efficacy (sedentary time, concentration, alertness, enjoyment). Movement breaks of five to 10 min duration were scheduled after 20 min of sedentary time during 2-h classes. Classes without movement breaks were used as a comparison. Data were collected using surveys, objective physical activity monitoring and focus group interviews of students (n = 85) and tutors (n = 6). Descriptive statistics (quantitative data) and independent coding and thematic analysis (qualitative data) were completed. Students (mean age 23 ± 2 years, 69% female) actively engaged in movement breaks with no adverse events. Movement breaks were perceived to be beneficial for concentration, engagement and productivity. Timing of the break was perceived to be important to enhance the benefit and reduce disruption. Students preferred outdoor or competitive movement breaks. Students spent 13 min less time sitting (95%CI 10 to 17), took 834 more steps (95%CI 675 to 994) and had higher levels of concentration, alertness and enjoyment (p < 0.001) in classes with movement breaks compared to classes without. Classroom movement breaks are feasible and may be considered for incorporation into university classes to reduce sedentary behaviour and increase physical activity, alertness, concentration and enjoyment.
Pain Status and Its Association with Physical Activity, Psychological Stress, and Telework among Japanese Workers with Pain during the COVID-19 Pandemic
Authors: Yoshimoto Takahiko , Fujii Tomoko , Oka Hiroyuki , Kasahara Satoshi , Kawamata Kayo , Matsudaira Ko
Published: May 2021

Changes in working styles and physical activities, and an increase in psychological stress during the coronavirus disease 2019 (COVID-19) pandemic, may have affected pain conditions among workers with pain; however, these associations are still poorly understood. Therefore, we conducted a web-based, cross-sectional study to investigate these changes among Japanese workers suffering from pain. A total of 1941 workers who were aged 20–64 years and suffered from body pain within 4 weeks prior to the study were included. Information was collected using a self-reported questionnaire between July and August 2020. Among the respondents, 15% reported that their pain worsened during the COVID-19 pandemic. Approximately half of the workers claimed to have decreased physical activity (47%) and increased psychological stress (47%) during the pandemic. Multivariable logistic regression analyses found that telework (odds ratio 2.27, 95% confidence interval 1.68–3.06), decreased physical activity (3.18, 2.38–4.27), and increased psychological stress (2.16, 1.64–2.84) were associated significantly with pain augmentation. The group of workers who participated in telework and had decreased physical activity comprised the highest proportion of those with augmented pain. Our findings suggest that measures, which consider physical activities, psychological aspects, and working styles, to alleviate pain may be required for the working population in the future.
Promoting Media Literacy Online: An Intervention on Performance and Appearance Enhancement Substances with Sport High School Students
Authors: Galli Federica , Palombi Tommaso , Mallia Luca , Chirico Andrea , Zandonai Thomas , Alivernini Fabio , De Maria Alessandra , Zelli Arnaldo , Lucidi Fabio
Published: May 2021

The outbreak of coronavirus required adjustment regarding the delivery of interventions. Media literacy interventions are necessary to help people acquire relevant skills to navigate the complexities of media communications, and to encourage health-promoting behaviors. The present study aimed to promote a media literacy intervention regarding performance and appearance enhancement substances use in sports high school students. The COVID-19 contingency allowed us to evaluate whether online sessions can effectively promote greater awareness of media influence, a stronger sense of confidence in persuading others to deal with media messages, and healthier attitudes about PAES use among high school students. The study relied on an “intervention group” comprising 162 students (31.5% female) and a “control group” comprising 158 students (42% female). Data were analyzed through repeated measures of Group X Time MANOVA and ANOVA, demonstrating some degree of efficacy of the media literacy intervention. The “intervention group” reported higher awareness of potential newspapers’ influence and a significant increase in their sense of confidence in dealing with media influence compared to the “control group”. Findings support the efficacy of online media literacy programs to prevent doping consumption in adolescents.
The Perspective of Physical Education Teachers in Spain Regarding Barriers to the Practice of Physical Activity among Immigrant Children and Adolescents: A Qualitative Study
Authors: Marconnot Romain , Pérez-Corrales Jorge , Cuenca-Zaldívar Juan Nicolás , Güeita-Rodríguez Javier , Carrasco-Garrido Pilar , García-Bravo Cristina , Solera-Hernández Eva , Gómez-Calcerrada Sonia Gutiérrez , Palacios-Ceña Domingo
Published: May 2021

Physical activity (PA) contributes to the development of children and adolescents and to their mental and physical health. The practice of PA in the school context can contribute towards generating a more inclusive educational community for immigrant children and adolescents. The aim of this study was to describe the perspectives of Spanish physical education (PE) teachers on the practice of PA among immigrant children and adolescents. This research was a qualitative exploratory study. A purposeful sampling strategy was used. Data were collected through semi-structured interviews and field notes. Twenty teachers were recruited. An inductive thematic analysis and content analysis were applied. The following topics were identified: (a) Professional expectations; (b) Economic resources; (c) Integration; (d) Family; (e) Religious beliefs and practices; and (f) Gender difference. A predominance of positive emotions was identified in the narratives, and the most repeated words in word clouds were ‘Caribbean’, ‘Latin’, and ‘population’. These findings help to identify PA barriers for immigrant children and adolescents and may contribute to the creation of PA-based interventions in social and educational contexts.
Temporal Trends in Notification and Mortality of Tuberculosis in China, 2004–2019: A Joinpoint and Age–Period–Cohort Analysis
Authors: Wang Luqi , Wang Weibing
Published: May 2021

Tuberculosis (TB) remains a major public health problem in China and worldwide. In this article, we used a joinpoint regression model to calculate the average annual percent change (AAPC) of TB notification and mortality in China from 2004 to 2019. We also used an age–period–cohort (APC) model based on the intrinsic estimator (IE) method to simultaneously distinguish the age, period and cohort effects on TB notification and mortality in China. A statistically downward trend was observed in TB notification and mortality over the period, with AAPCs of −4.2% * (−4.9%, −3.4%) and −5.8% (−7.5%, −4.0%), respectively. A bimodal pattern of the age effect was observed, peaking in the young adult (aged 15–34) and elderly (aged 50–84) groups. More specifically, the TB notification risk populations were people aged 20–24 years and 70–74 years; the TB mortality risk population was adults over the age of 60. The period effect suggested that TB notification and mortality risks were nearly stable over the past 15 years. The cohort effect on both TB notification and mortality presented a continuously decreasing trend, and it was no longer a risk factor after 1978. All in all, the age effect should be paid more attention.
Non-Obese MAFLD Is Associated with Colorectal Adenoma in Health Check Examinees: A Multicenter Retrospective Study
Authors: Fukunaga Shuhei , Nakano Dan , Kawaguchi Takumi , Eslam Mohammed , Ouchi Akihiro , Nagata Tsutomu , Kuroki Hidefumi , Kawata Hidemichi , Abe Hirohiko , Nouno Ryuichi , Kawaguchi Koutaro , George Jacob , Mitsuyama Keiichi , Torimura Takuji
Published: May 2021

Colorectal adenoma is linked to metabolic dysfunction. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a precise definition and three subtypes, including non-obese MAFLD. We aimed to investigate the impact of MAFLD on the prevalence of colorectal adenoma by comparing it to non-alcoholic fatty liver disease (NAFLD) in health check-up examinees. This is a multicenter retrospective study. We enrolled 124 consecutive health check-up examinees who underwent colonoscopy. NAFLD and MAFLD were present in 58 and 63 examinees, respectively. Colorectal adenoma was diagnosed by biopsy. The impact of the MAFLD definition on the prevalence of colorectal adenoma was investigated by logistic regression, decision-tree, and random forest analyses. In logistic regression analysis, MAFLD was identified as the only independent factor associated with the presence of colorectal adenoma (OR 3.191; 95% CI 1.494–7.070; p = 0.003). MAFLD was also identified as the most important classifier for the presence of colorectal adenoma in decision-tree and random forest analyses (29 variable importance value). Among the three subtypes of MAFLD, non-obese MAFLD was the sole independent factor associated with the presence of colorectal adenoma (OR 3.351; 95% CI 1.589–7.262; p ≤ 0.001). Non-obese MAFLD was also the most important classifier for the presence of colorectal adenoma in decision-tree and random forest analyses (31 variable importance value). MAFLD, particularly non-obese MAFLD, is the most important factor associated with the presence of colorectal adenoma rather than NAFLD. Colonoscopy examination should be considered in patients with MAFLD, especially those who are non-obese.
Improved Identification of Small Open Reading Frames Encoded Peptides by Top-Down Proteomic Approaches and De Novo Sequencing
Authors: Wang Bing , Wang Zhiwei , Pan Ni , Huang Jiangmei , Wan Cuihong
Published: May 2021

Small open reading frames (sORFs) have translational potential to produce peptides that play essential roles in various biological processes. Nevertheless, many sORF-encoded peptides (SEPs) are still on the prediction level. Here, we construct a strategy to analyze SEPs by combining top-down and de novo sequencing to improve SEP identification and sequence coverage. With de novo sequencing, we identified 1682 peptides mapping to 2544 human sORFs, which were all first characterized in this work. Two-thirds of these new sORFs have reading frame shifts and use a non-ATG start codon. The top-down approach identified 241 human SEPs, with high sequence coverage. The average length of the peptides from the bottom-up database search was 19 amino acids (AA); from de novo sequencing, it was 9 AA; and from the top-down approach, it was 25 AA. The longer peptide positively boosts the sequence coverage, more efficiently distinguishing SEPs from the known gene coding sequence. Top-down has the advantage of identifying peptides with sequential K/R or high K/R content, which is unfavorable in the bottom-up approach. Our method can explore new coding sORFs and obtain highly accurate sequences of their SEPs, which can also benefit future function research.
Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study
Authors: Kannan Siddarth , O’Connor Geraldine Martina , Bakker Emyr Yosef
Published: May 2021

Immune checkpoint blockade targeting PD-1 (PDCD1)/PD-L1 (CD274) is increasingly used for multiple cancers. However, efficacy and adverse-related events vary significantly. This bioinformatic study interrogated molecular differences pertaining to PDCD1/CD274 and their correlated genes on a pan-cancer basis to identify differences between cancer types. Patient RNA-seq data from fifteen cancer types were accessed on cBioPortal to determine the role of PDCD1/CD274 in patient survival and to identify positively and negatively correlated genes, which were also assessed for clinical relevance. Genes correlating with PDCD1/CD274 across multiple cancers were taken forward for drug repurposing via DRUGSURV and microRNA analysis using miRDB and miRabel. MicroRNAs were also screened for clinical relevance using OncomiR. Forty genes were consistently correlated with PDCD1/CD274 across multiple cancers, with the cancers themselves exhibiting a differential role for the correlated genes in terms of patient survival. Esophageal and renal cancers in particular stood out in this regard as having a unique survival profile. Forty-nine putative microRNAs were identified as being linked to the PDCD1/CD274 network, which were taken forward and further assessed for clinical relevance using OncomiR and previously published literature. One hundred and thirty significant survival associations for 46 microRNAs across fourteen groups of cancers were identified. Finally, a total of 23 putative repurposed drugs targeting multiple components of the PDCD1/CD274 network were identified, which may represent immunotherapeutic adjuvants. Taken together, these results shed light on the varying PDCD1/CD274 networks between individual cancers and signpost a need for more cancer-specific investigations and treatments.
Ubiquitination and Deubiquitination in Oral Disease
Authors: Tsuchida Sachio , Nakayama Tomohiro
Published: May 2021

Oral health is an integral part of the general health and well-being of individuals. The presence of oral disease is potentially indicative of a number of systemic diseases and may contribute to their early diagnosis and treatment. The ubiquitin (Ub) system has been shown to play a role in cellular immune response, cellular development, and programmed cell death. Ubiquitination is a post-translational modification that occurs in eukaryotes. Its mechanism involves a number of factors, including Ub-activating enzymes, Ub-conjugating enzymes, and Ub protein ligases. Deubiquitinating enzymes, which are proteases that reversely modify proteins by removing Ub or Ub-like molecules or remodeling Ub chains on target proteins, have recently been regarded as crucial regulators of ubiquitination-mediated degradation and are known to significantly affect cellular pathways, a number of biological processes, DNA damage response, and DNA repair pathways. Research has increasingly shown evidence of the relationship between ubiquitination, deubiquitination, and oral disease. This review investigates recent progress in discoveries in diseased oral sites and discusses the roles of ubiquitination and deubiquitination in oral disease.
Demethoxycurcumin Suppresses Human Brain Glioblastoma Multiforme GBM 8401 Cell Xenograft Tumor in Nude Mice In Vivo
Authors: Huang Yi-Ping , Ma Yi-Shih , Kuo Chao-Lin , Liao Ching-Lung , Chen Po-Yuan , Peng Shu-Fen , Hsu Fei-Ting , Lai Kuang-Chi
Published: May 2021

Demethoxycurcumin (DMC), a derivate of curcumin, has been shown to induce apoptotic cell death in human glioblastoma multiforme GBM 8401 cells via cell cycle arrest and induction of cell apoptosis. However, there is no report showing DMC suppresses glioblastoma multiforme cells in vivo. In the present study, we investigated the effects of DMC on GBM8401 cells in vivo. At first, we established a luciferase-expressing stable clone named GBM 8401/luc2. Second, mice were inoculated subcutaneously with GBM 8401/luc2 cells to generate a xenograft tumor mice model. After inoculation, tumor volume reached 100–120 mm3, and all mice were randomly divided into three groups: Group I was treated with 110 µL phosphate-buffered solution (PBS) containing 0.1% dimethyl sulfoxide, Group II with 30 mg/kg of DMC, and Group III with 60 mg/kg of DMC. Mice from each group were given the oral treatment of DMC by gavage for 21 days. The body weight and tumor volume were recorded every 3 days. DMC significantly decreased the tumor volumes, and 60 mg/kg treatment showed a higher decrease in tumor volumes than that of 30 mg/kg, However, DMC did not affect the body weights. The photons emitted from mice tumors were detected with Xenogen IVIS imaging system, DMC at both doses decreased the total photon flux and 60 mg/kg treatment of DMC has low total photon flux than that of 30 mg/kg. The tumor volumes and weights in 60 mg/kg treatment of DMC were lower than that of 30 mg/kg. Immunohistochemical analysis was used to measure protein expression of tumors and results showed that DMC treatment led to lightly staining with anti-Bcl-2 and -XIAP and 60 mg/kg treatment of DMC has lighter staining with anti-Bcl-2 and -XIAP than that of 30 mg/kg. The higher dose (60 mg/kg) of DMC has higher signals of cleaved-caspase-3 than that of the lower dose (30 mg/kg). Furthermore, the hematoxylin and eosin (H&E) staining of liver tissues showed no significant difference between DMC-treated and control-groups. Overall, these observations showed that DMC suppressed tumor properties in vivo and DMC may be used against human glioblastoma multiforme in the future.
DeepD2V: A Novel Deep Learning-Based Framework for Predicting Transcription Factor Binding Sites from Combined DNA Sequence
Authors: Deng Lei , Wu Hui , Liu Xuejun , Liu Hui
Published: May 2021

Predicting in vivo protein–DNA binding sites is a challenging but pressing task in a variety of fields like drug design and development. Most promoters contain a number of transcription factor (TF) binding sites, but only a small minority has been identified by biochemical experiments that are time-consuming and laborious. To tackle this challenge, many computational methods have been proposed to predict TF binding sites from DNA sequence. Although previous methods have achieved remarkable performance in the prediction of protein–DNA interactions, there is still considerable room for improvement. In this paper, we present a hybrid deep learning framework, termed DeepD2V, for transcription factor binding sites prediction. First, we construct the input matrix with an original DNA sequence and its three kinds of variant sequences, including its inverse, complementary, and complementary inverse sequence. A sliding window of size k with a specific stride is used to obtain its k-mer representation of input sequences. Next, we use word2vec to obtain a pre-trained k-mer word distributed representation model. Finally, the probability of protein–DNA binding is predicted by using the recurrent and convolutional neural network. The experiment results on 50 public ChIP-seq benchmark datasets demonstrate the superior performance and robustness of DeepD2V. Moreover, we verify that the performance of DeepD2V using word2vec-based k-mer distributed representation is better than one-hot encoding, and the integrated framework of both convolutional neural network (CNN) and bidirectional LSTM (bi-LSTM) outperforms CNN or the bi-LSTM model when used alone. The source code of DeepD2V is available at the github repository.
Circulating Tumor DNA Testing for Homology Recombination Repair Genes in Prostate Cancer: From the Lab to the Clinic
Authors: Cimadamore Alessia , Cheng Liang , Massari Francesco , Santoni Matteo , Pepi Laura , Franzese Carmine , Scarpelli Marina , Lopez-Beltran Antonio , Galosi Andrea Benedetto , Montironi Rodolfo
Published: May 2021

Approximately 23% of metastatic castration-resistant prostate cancers (mCRPC) harbor deleterious aberrations in DNA repair genes. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) therapy has shown improvements in overall survival in patients with mCRPC who harbor somatic and/or germline alterations of homology recombination repair (HRR) genes. Peripheral blood samples are typically used for the germline mutation analysis test using the DNA extracted from peripheral blood leucocytes. Somatic alterations can be assessed by extracting DNA from a tumor tissue sample or using circulating tumor DNA (ctDNA) extracted from a plasma sample. Each of these genetic tests has its own benefits and limitations. The main advantages compared to the tissue test are that liquid biopsy is a non-invasive and easily repeatable test with the value of better representing tumor heterogeneity than primary biopsy and of capturing changes and/or resistance mutations in the genetic tumor profile during disease progression. Furthermore, ctDNA can inform about mutation status and guide treatment options in patients with mCRPC. Clinical validation and test implementation into routine clinical practice are currently very limited. In this review, we discuss the state of the art of the ctDNA test in prostate cancer compared to blood and tissue testing. We also illustrate the ctDNA testing workflow, the available techniques for ctDNA extraction, sequencing, and analysis, describing advantages and limits of each techniques.
P2Y2R Deficiency Ameliorates Hepatic Steatosis by Reducing Lipogenesis and Enhancing Fatty Acid β-Oxidation through AMPK and PGC-1α Induction in High-Fat Diet-Fed Mice
Authors: Dusabimana Theodomir , Park Eun Jung , Je Jihyun , Jeong Kyuho , Yun Seung Pil , Kim Hye Jung , Kim Hwajin , Park Sang Won
Published: May 2021

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease associated with obesity and insulin resistance. Activation of the purinergic receptor P2Y2R has been reported to promote adipogenesis, inflammation and dyslipidemia in adipose tissues in obese mice. However, the role of P2Y2R and its mechanisms in NAFLD remain unknown. We hypothesized that P2Y2R deficiency may play a protective role in NAFLD by modulating lipid metabolism in the liver. In this study, we fed wild type and P2Y2R knockout mice with a high-fat diet (HFD) for 12 weeks and analyzed metabolic phenotypes. First, P2Y2R deficiency effectively improved insulin resistance with a reduction in body weight and plasma insulin. Second, P2Y2R deficiency attenuated hepatic lipid accumulation and injury with reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Third, P2Y2R deficiency decreased the expression of fatty acid synthesis mediators (cluster of differentiation (CD36), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1)); and increased the expression of adipose triglyceride lipase (ATGL), a lipolytic enzyme. Mechanistically, P2Y2R deficiency increased the AMP-activated protein kinase (AMPK) activity to improve mitochondrial fatty acid β-oxidation (FAO) by regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1A (CPT1A)-mediated FAO pathway. In addition, P2Y2R deficiency increased peroxisome proliferator-activated gamma co-activator-1α (PGC-1α)-mediated mitochondrial biogenesis. Conclusively, P2Y2R deficiency ameliorated HFD-induced hepatic steatosis by enhancing FAO through AMPK signaling and PGC-1α pathway, suggesting P2Y2R as a promising therapeutic target for NAFLD.
Migraine and Sleep—An Unexplained Association?
Authors: Waliszewska-Prosół Marta , Nowakowska-Kotas Marta , Chojdak-Łukasiewicz Justyna , Budrewicz Sławomir
Published: May 2021

Migraine and sleep disorders are common chronic diseases in the general population, with significant negative social and economic impacts. The association between both of these phenomena has been observed by clinicians for years and is confirmed by many epidemiological studies. Despite this, the nature of this relationship is still not fully understood. In recent years, there has been rapid progress in understanding the common anatomical structures of and pathogenetic mechanism between sleep and migraine. Based on a literature review, the authors present the current view on this topic as well as ongoing research in this field, with reference to the key points of the biochemical and neurophysiological processes responsible for both these disorders. In the future, a better understanding of these mechanisms will significantly expand the range of treatment options.
Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression
Authors: Eichelmann Ann-Kathrin , Mayne George C. , Chiam Karen , Due Steven L. , Bastian Isabell , Butz Frederike , Wang Tingting , Sykes Pamela J. , Clemons Nicholas J. , Liu David S. , Michael Michael Z. , Karapetis Christos S. , Hummel Richard , Watson David I. , Hussey Damian J.
Published: May 2021

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.
Generation of GCaMP6s-Expressing Zebrafish to Monitor Spatiotemporal Dynamics of Calcium Signaling Elicited by Heat Stress
Authors: Li Fengyang , Long Yong , Xie Juhong , Ren Jing , Zhou Tong , Song Guili , Li Qing , Cui Zongbin
Published: May 2021

The ability of organisms to quickly sense and transduce signals of environmental stresses is critical for their survival. Ca2+ is a versatile intracellular messenger involved in sensing a wide variety of stresses and regulating the subsequent cellular responses. So far, our understanding for calcium signaling was mostly obtained from ex vivo tissues and cultured cell lines, and the in vivo spatiotemporal dynamics of stress-triggered calcium signaling in a vertebrate remains to be characterized. Here, we describe the generation and characterization of a transgenic zebrafish line with ubiquitous expression of GCaMP6s, a genetically encoded calcium indicator (GECI). We developed a method to investigate the spatiotemporal patterns of Ca2+ events induced by heat stress. Exposure to heat stress elicited immediate and transient calcium signaling in developing zebrafish. Cells extensively distributed in the integument of the head and body trunk were the first batch of responders and different cell populations demonstrated distinct response patterns upon heat stress. Activity of the heat stress-induced calcium signaling peaked at 30 s and swiftly decreased to near the basal level at 120 s after the beginning of exposure. Inhibition of the heat-induced calcium signaling by LaCl3 and capsazepine and treatment with the inhibitors for CaMKII (Ca²2/calmodulin-dependent protein kinase II) and HSF1 (Heat shock factor 1) all significantly depressed the enhanced heat shock response (HSR). Together, we delineated the spatiotemporal dynamics of heat-induced calcium signaling and confirmed functions of the Ca2+-CaMKII-HSF1 pathway in regulating the HSR in zebrafish.
Induced Pluripotent Stem Cell-Derived Conditioned Medium Promotes Endogenous Leukemia Inhibitory Factor to Attenuate Endotoxin-Induced Acute Lung Injury
Authors: Su Vincent Yi-Fong , Chiou Shih-Hwa , Chen Wei-Chih , Yu Wen-Kuang , Wu Huai-Hsuan , Chen Hao , Yang Kuang-Yao
Published: May 2021

The conditioned medium of induced pluripotent stem cells (iPSC-CM) can attenuate neutrophil recruitment and endothelial leakage of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Therefore, we investigated the mechanisms by which iPSC-CM regulate the interaction between neutrophils and the endothelium in ALI. Murine iPSCs (miPSCs) were delivered intravenously to male C57BL/6 mice (8–12 weeks old) 4 h after intratracheal LPS injection. A miPSC-derived conditioned medium (miPSC-CM) was delivered intravenously to mice after intratracheal LPS injection. DMSO-induced HL-60 cells (D-HL-60, neutrophil-like cells) and human umbilical vein endothelial cells (HUVECs) were used as in vitro models to assess the interaction of neutrophils and endothelial cells. miPSC-CM diminished the histopathological changes in the lungs and the neutrophil count in bronchoalveolar lavage fluids of ALI mice. miPSC-CM attenuated the expression of adhesion molecules in the lungs of ALI mice. Human iPSC conditioned medium (hiPSC-CM) reduced the expression of adhesion molecules in a HUVEC and D-HL-60 co-culture after LPS stimulation, which decreased the transendothelial migration (TEM) of D-HL-60. A human angiogenesis factors protein array revealed that leukemia inhibitory factor (LIF) was not detected in the absence of D-HL-60 and hiPSC-CM groups. hiPSC-CM significantly promoted the production of endogenous LIF in in vitro models. Administration of an anti-LIF antibody not only reversed the effect of iPSC-CM in ALI mice, but also blocked the effect of iPSC-CM on neutrophils TEM in in vitro models. However, a controlled IgG had no such effect. Our study demonstrated that iPSC-CM promoted endogenous LIF to inhibit neutrophils TEM and attenuate the severity of sepsis-induced ALI.
Massachusetts’ Findings from Statewide Newborn Screening for Spinal Muscular Atrophy
Authors: Hale Jaime E. , Darras Basil T. , Swoboda Kathryn J. , Estrella Elicia , Chen Jin Yun Helen , Abbott Mary-Alice , Hay Beverly N. , Kumar Binod , Counihan Anne M. , Gerstel-Thompson Jacalyn , Sahai Inderneel , Eaton Roger B. , Comeau Anne Marie
Published: May 2021

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent SMN1 Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life). Another ten SMN1 hybrids were observed but never referred. The nine referred infants who were confirmed to have SMA were entered into treatment protocols. Early data show that some SMA-affected children have remained asymptomatic and are meeting developmental milestones and some have mild to moderate delays. The Massachusetts experience demonstrates that SMA NBS is feasible, can be implemented on a population basis, and helps engage infants for early treatment to maximize benefit.