bluuebunny/crossref_metadata_2025 huggingface dataset:
Tough and Resilient Hydrogels Enabled by a Multifunctional Initiating and Cross-Linking Agent
Authors: Cao Zhenxing , Yuan Zhaoyang , Wu Rui , Wu Haitao , Jin Biqiang , Zheng Jing , Wu Jinrong
Published: October 2021

Many high-strength hydrogels have been developed in recent years; however, few of them are both tough and resilient, and their intrinsic paradoxical nature makes designing a gel with both high toughness and high resilience a great challenge. To address this problem, we introduced both N,N,N,N-pentamethyldiethylenetriamine (PA) and N,N-methylenebisacrylamide (MBA) into polyacrylamide hydrogel networks to construct an entangled network that contains chemically cross-linked chains and branched chains simultaneously. The entanglements of branched chains can act as a physical cross-linking point to uniformly disperse stress on molecular chains, and chemical cross-linking ensures the stability of the hydrogel network. The increase in the number and length of branched chains is able to achieve an enhancement in strength while the slip of the entangled polymer chains can effectively achieve energy dissipation and can improve the toughness of the gel. Moreover, the resultant hydrogels exhibit an excellent resilience (>98%). Therefore, high toughness and resilience are achieved simultaneously. In addition, we also investigated the initiation mechanism of PA. This strategy creates a new way for the preparation of next-generation high toughness and high resilience hydrogel-based materials, which have promising applications in wearable, flexible strain/pressure sensors.
Regulatory Single Nucleotide Polymorphism of the Bovine IFITM3 Gene Induces Differential Transcriptional Capacities of Hanwoo and Holstein Cattle
Authors: Kim Yong-Chan , Jeong Min-Ju , Jeong Byung-Hoon
Published: October 2021

Interferon-induced transmembrane protein 3 (IFITM3), a crucial effector of the host’s innate immune system, prohibits an extensive range of viruses. Previous studies have reported that single nucleotide polymorphisms (SNPs) of the IFITM3 gene are associated with the expression level and length of the IFITM3 protein and can impact susceptibility to infectious viruses and the severity of infection with these viruses. However, there have been no studies on polymorphisms of the bovine IFITM3 gene. In the present study, we finely mapped the bovine IFITM3 gene and annotated the identified polymorphisms. We investigated polymorphisms of the bovine IFITM3 gene in 108 Hanwoo and 113 Holstein cattle using direct sequencing and analyzed genotype, allele, and haplotype frequencies and linkage disequilibrium (LD) between the IFITM3 genes of the two cattle breeds. In addition, we analyzed transcription factor-binding sites and transcriptional capacity using PROMO and luciferase assays, respectively. Furthermore, we analyzed the effect of a nonsynonymous SNP of the IFITM3 gene using PolyPhen-2, PANTHER, and PROVEAN. We identified 23 polymorphisms in the bovine IFITM3 gene and found significantly different genotype, allele, and haplotype frequency distributions and LD scores between polymorphisms of the bovine IFITM3 gene in Hanwoo and Holstein cattle. In addition, the ability to bind the transcription factor Nkx2-1 and transcriptional capacities were significantly different depending on the c.-193T > C allele. Furthermore, nonsynonymous SNP (F121L) was predicted to be benign. To the best of our knowledge, this is the first genetic study of bovine IFITM3 polymorphisms.
A Call for More Snow Sampling
Authors: Fassnacht Steven R.
Published: October 2021

The snowpack is important for water resources, tourism, ecology, and the global energy budget. Over the past century, we have gone from point measurements of snow water equivalent (SWE) to estimate spring and summer runoff volumes, to remote sensing of various snowpack properties at continuously finer spatial and temporal resolutions, to various complexities of snowpack and hydrological modeling, to the current fusion of field data with remote sensing and modeling, all to improve our estimates of the snowpack and the subsequent runoff. However, we are still limited by the uncertainty induced by scaling from point field measurements to the area represented by remote sensing and modeling. This paper uses several examples of fine-resolution sampling to issue a call to snow hydrologists and other earth scientists to collect more data, or at least to thoroughly evaluate their sampling strategy for collecting ground-truth measurements. Recommendations are provided for different approaches to have more representative sampling, when at all possible, to collect at least a few more samples or data points.
Disparities across Diverse Populations in the Health and Treatment of Patients with Osteoarthritis
Authors: Faison Warachal E. , Harrell P. Grace , Semel David
Published: October 2021

The study of disparities across diverse populations regarding the health and treatment of patients with osteoarthritis (OA) is recognized as a priority for investigation and action by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the American Academy of Orthopedic Surgeons (AAOS). OA is a common condition that increases with age, but with prevalence generally similar across racial and ethnic groups. However, disparities in the treatment of OA among racial, ethnic, and socioeconomic groups are well-documented and continue to rise and persist. The reasons are complex, likely involving a combination of patient, provider, and healthcare system factors. Treatment disparities among these different populations have an impact on clinical outcomes, healthcare, and productivity, and are projected to increase significantly with the growing diversity of the United States population. The aim of this short review is to summarize studies of racial, ethnic, and socioeconomic disparities among patients with OA in the United States, with a focus on prevalence, treatment utilization, and clinical and economic outcomes.
Water Stress in Dwarfing Cherry Rootstocks: Increased Carbon Partitioning to Roots Facilitates Improved Tolerance of Drought
Authors: Wheeler Will , Black Brent , Bugbee Bruce
Published: October 2021

Cherry orchards are transitioning to high-density plantings and dwarfing rootstocks to maximize production, but the response of these rootstocks to drought stress is poorly characterized. We used a 16-container, automated lysimeter system to apply repeated water stress to ungrafted Krymsk® 5 and 6 rootstocks during two growing cycles. Drought stress was imposed by withholding irrigation until the daily transpiration rate of each tree was 25% and 30% of the unstressed rate during the first trial and second trial, respectively. After this point was reached, the root-zone water status was restored to field capacity. Whole-tree transpiration measurements were supplemented with leaf-level gas-exchange measurements. Krymsk® 6 had a higher rate of photosynthesis, more vigorous vegetative growth and less conservative stomatal regulation during incipient drought than Krymsk® 5. At harvest, carbon partitioning to roots was greater in Krymsk® 6 than Krymsk® 5. The conservative rate of water use in Krymsk® 5 could be a function of greater stomatal control or reduced carbon partitioning to roots, which thereby limited transpiration rates. Further studies are needed to confirm that these results are applicable to trees grown using a common grafted scion under field conditions.
Changes in Sugar Accumulation and Related Enzyme Activities of Red Bayberry (Myrica rubra) in Greenhouse Cultivation
Authors: Wu Bo-Ping , Zhang Cong , Gao Yong-Bin , Zheng Wei-Wei , Xu Kai
Published: October 2021

The harvest period of bayberry fruit cultivated in the open field is short and often suffers from continuous cloudy and rainy days, leading to a decrease in yield and a decline in fruit quality. However, cultivating bayberries in greenhouses could avoid the harm due to rain, improve fruit quality and prolong the supply period, thus significantly increasing economic returns. Bayberry fruit quality, assessed by single fruit weight, vertical and horizontal diameters, soluble solids content and sugar-acid ratios, was significantly superior in fruit produced under greenhouse conditions than in fruit produced in the open field. Analysis of the soluble sugar components and the related enzyme activities indicated that the sucrose accumulation and metabolism of bayberry fruit were significantly improved by greenhouse cultivation, possibly owing to differences in sucrose-phosphate synthase and acid invertase activities.
The Combined Effect of Pseudomonas stutzeri and Biochar on the Growth Dynamics and Tolerance of Lettuce Plants (Lactuca sativa) to Cadmium Stress
Authors: Elbagory Mohssen , Farrag Diaa K. , Hashim Ahmed M. , Omara Alaa El-Dein
Published: October 2021

Agricultural activities lead to the accumulation of cadmium (Cd) in the soil. It is necessary to identify effective and economical ways to reduce the soil Cd bioavailability. To achieve this, three bacterial strains, Pseudomonas stutzeri, P. koreensis, and P. fluorescens, were tested for tolerance and biosorption of different concentrations of Cd (0, 5, 10, 15, 20, and 25 mg L−1). During the 2020 and 2021 seasons, a pot experiment was conducted using four different soil amendments (control, biochar, P. stutzeri, and a combination) under four levels of Cd (0, 40, 80, and 120 mg kg−1) and assessing the effect on growth parameters, physiological modifications, antioxidant enzymes, and Cd accumulation in lettuce plants (Lactuca sativa cv. Balady). In vitro, the results showed that P. stutzeri was the most tolerant of Cd. Our findings in pot trials showed that T4 (biochar + P. stutzeri) was a more efficient treatment in terms of the growth parameters, with 452.00 g plant−1 was recorded for fresh weight, 40.10 g plant−1 for dry weight, 18.89 cm plant−1 for plant height, 6.03 cm2 for leaf area, and 20.48 for the number of leaves plant−1, while in terms of physiological characteristics, we recorded 1.29 mg g−1 FW, 0.35 μg g−1 FW, and 3.69 μg g−1 FW for total chlorophyll, carotenoids, and total soluble sugar, respectively; this was also reflected in the number of antioxidant enzymes and intensity of soil biological activities in soil treated with 120 mg kg−1 Cd compared with the control and other treatments in the first season. A similar trend was observed in the second season. Additionally, significantly lower Cd was observed in both the root (67%) and shoots (78%). Therefore, a combined application of biochar and P. stutzeri could be used as an alternative to mitigate Cd toxicity.
Assessment of Oral Chemotherapy Nonadherence in Chronic Myeloid Leukemia Patients Using Brief Measures in Community Cancer Clinics: A Pilot Study
Authors: Davis Terry C. , Arnold Connie L. , Mills Glenn , Lesser Glenn J. , Brown W. Mark , Schulz Richard , Weaver Kathryn E. , Pawloski Pamala A.
Published: October 2021

The purpose of this pilot study was to assess Chronic Myeloid Leukemia (CML) patients’ adherence to, beliefs about, and barriers to oral anticancer agents (OAC) using brief self-report measures in community-based cancer clinics. Patients completed a structured interview including a health literacy assessment, a Brief Medication Questionnaire, two single-item self-report adherence questions, and the Medications Adherence Reasons Scale. Of the 86 participants, 88.4% were white; 55.8% male; mean age, 58.7 years; and 22.1% had limited health literacy. Nonadherence (missing at least one dose in the last week) was reported by 18.6% of participants and associated (p < 0.003) with less-than-excellent perceived ability to take CML medications (16.3%). Black participants reported more difficulty taking CML medications than white participants (28.6% vs. 8.3%, p = 0.053). Among all participants, 43.0% reported their CML medicine was ineffective and 24.4% that taking CML pills was somewhat to very hard. The most common reasons for missing a dose were simply missed it (24.4%) and side effects (18.6%). Most patients perceived their ability to take CML medication was good to excellent, yet nearly one in five reported missing at least one dose in the last week. Brief, no-cost self-report assessments to screen CML patients’ OAC adherence, barriers, and beliefs could facilitate counseling in busy community cancer clinics.
Nursing Interventions for Patient Empowerment during Intensive Care Unit Discharge: A Systematic Review
Authors: Cuzco Cecilia , Torres-Castro Rodrigo , Torralba Yolanda , Manzanares Isabel , Muñoz-Rey Pilar , Romero-García Marta , Martínez-Momblan Ma. Antonia , Martínez-Estalella Gemma , Delgado-Hito Pilar , Castro Pedro
Published: October 2021

Intensive care unit discharge is an important transition that impacts a patient’s wellbeing. Nurses can play an essential role in this scenario, potentiating patient empowerment. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (the PRISMA Statement. Embase), PubMed/MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), CUIDEN Plus, and LILACS databases; these were evaluated in May 2021. Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of evidence. Quality of the studies included was assessed using the Cochrane risk-of-bias tool. Of the 274 articles initially identified, eight randomized controlled trials that reported on nursing interventions had mainly focused on patients’ ICU discharge preparation through information and education. The creation of ICU nurse-led teams and nurses’ involvement in critical care multidisciplinary teams also aimed to support patients during ICU discharge. This systematic review provides an update on the clinical practice aimed at improving the patient experience during ICU discharge. The main nursing interventions were based on information and education, as well as the development of new nursing roles. Understanding transitional needs and patient empowerment are key to making the transition easier.
Ethics of Gamification in Health and Fitness-Tracking
Authors: Arora Chirag , Razavian Maryam
Published: October 2021

The use of game-like elements is become increasingly popular in the context of fitness and health apps. While such “gamified” apps hold great potential in motivating people to improve their health, they also come with a “darker side”. Recent work suggests that these gamified health apps raise a number of ethical challenges that, if left unaddressed, are not only morally problematic but also have adverse effects on user health and engagement with the apps. However, studies highlighting the ethical challenges of gamification have also met with criticism, indicating that they fall short of providing guidance to practitioners. In avoiding this mistake, this paper seeks to advance the goal of facilitating a practice-relevant guide for designers of gamified health apps to address ethical issues raised by use of such apps. More specifically, the paper seeks to achieve two major aims: (a) to propose a revised practice-relevant theoretical framework that outlines the responsibilities of the designers of gamified health apps, and (b) to provide a landscape of the various ethical issues related to gamified health apps based on a systematic literature review of the empirical literature investigating adverse effects of such apps.
The Influence of Robot-Assisted Learning System on Health Literacy and Learning Perception
Authors: Wei Chun-Wang , Kao Hao-Yun , Wu Wen-Hsiung , Chen Chien-Yu , Fu Hsin-Pin
Published: October 2021

Healthy aging is a new challenge for the world. Therefore, health literacy education is a key issue in the current health care field. This research has developed a robot-assisted learning system to explore the possibility of significantly improving health literacy and learning perception through interaction with robots. In particular, this study adopted an experimental design, in which the experiment lasted for 90 min. A total of 60 participants over the age of 50 were randomly assigned to different learning modes. The RobotLS group learned by interacting with robots, while the VideoLS group watched health education videos on a tablet computer. The content dealt with hypertension related issues. This study used the European Health Literacy Survey Questionnaire (HLS-EU-Q16), Health Knowledge Questionnaire, Reduced Instructional Materials Motivation Survey (RIMMS), and Flow Scale as evaluation tools. The result shows no significant difference in the pre-test scores between the two groups. Compared with the video-assisted learning system, the robot-assisted learning system can significantly improve health knowledge, health literacy, learning motivation, and flow perception. According to the findings of this study, a robot-assisted learning system can be introduced in the future into homes and care institutions to enhance the health literacy of the elderly.
Differences in Student Brain Activation from Digital Learning Based on Risk of Digital Media Addiction
Authors: Seomun GyeongAe , Noh Wonjung
Published: October 2021

Although digital media usage is prevalent among middle school students, the safety of digital media-based learning activities for students at risk of digital media addiction is unknown. The goal of this study was to evaluate the differences in students’ brain activity in relation to their risk of digital media addiction. The study was quasi-experimental, with a pre- to post-test control group design. The study participants included 83 middle school students who were engaged in digital learning. We measured their brainwaves to evaluate brain activity using a PolyG-I (LAXTHA Inc.). We found no statistically significant differences in the location of the attention index between the two groups before and after digital learning. However, there were statistically significant differences between the two groups in the P3, P4, and F4 locations of the relaxation index. These results indicate that students at risk of digital media addiction may experience learning difficulties. These results can be used to guide healthcare professionals in developing digital learning programs that are safe for students and to also verify the effects of these programs.
Contextual Determinants of General Household Hygiene Conditions in Rural Indonesia
Authors: Daniel D.
Published: October 2021

Household hygiene is critical to prevent pathogen transmission at the household level. Assessing household hygiene conditions and their determinants are needed to improve hygiene conditions, especially in rural and less developed areas where the housing conditions are relatively worse than they are in urban areas. This study used data from 278 household interviews and observations in rural areas in the district of East Sumba, province East Nusa Tenggara, Indonesia. The data were analyzed using statistical methods. In general, the household hygiene conditions in the study need to be improved. The main potential sources of pathogen transmission were from the surrounding environment, i.e., non-permanent floor and garbage, and personal hygiene, i.e., handwashing facilities with water and soap were only observed in the homes of four out of ten respondents. The presence of livestock roaming freely in the house’s yard was another source of contamination. Easy access to water and wealth significantly influenced the hygiene conditions. Implementing low-cost interventions, i.e., cleaning the house of garbage and animal feces and cleaning nails, should be the priority in immediate intervention, while providing easier access to water supply, especially during the dry season, could be a long-term intervention. This paper also argues that analyzing household hygiene conditions or practices should be complemented by analyzing contextual determinants of the hygiene conditions or practices, so that we can develop more precise intervention by considering the local or household context.
Distress Levels of Parents of Children with Neurodevelopmental Disorders during the COVID-19 Pandemic: A Comparison between Italy and Australia
Authors: Burnett Dayle , Masi Anne , Mendoza Diaz Antonio , Rizzo Renata , Lin Ping-I , Eapen Valsamma
Published: October 2021

Parents of children with a neurodevelopmental disorder (NDD) report higher levels of distress compared to those of typically developing children. Distress levels may be heightened by the restrictions associated with the COVID-19 pandemic. However, it is unclear whether distress levels of parents varied by the diagnosis of neurodevelopmental disorder in children during the COVID-19 pandemic. This study aims to investigate whether parental distress was influenced by the type of NDD. Participants were from Australia (N = 196) and Italy (N = 200); the parents of children aged 3–18 were invited to complete an online self-reported survey which included the 6-item Kessler Psychological Distress Scale (K6) to determine parental distress. The results show that intellectual or learning disorder (ILD) is a major contributor to parental distress compared to other NDDs in both Australia and Italy. Moreover, the worsening of symptomatic changes in children with NDDs was significantly associated with parental distress. The differences between the two countries in terms of the pandemic impact, however, were not statistically significant. The results suggest that intervention strategies need to be tailored for individual clinical information and factor in the society’s stringency level of anti-contagion policies to improve parental wellbeing.
Predictive Model of Preventive Behaviors against COVID-19 in the Older Adult: The PREASOC-COVID-19 Study
Authors: Sarabia-Cobo Carmen María , Delgado Uria Aroa , García Lecue Marta , Izaguirre Palazuelos Eva , Martínez Ruiz César , Fernández-Rodríguez Ángela
Published: October 2021

Background: The purpose of this study was to analyze the relationship between COVID-19 preventive behaviors, as the dependent variable, with risk perception, coping style and sense of coherence, as independent variables, in older people living in the community. Methods: An observational design for predictive model development. This study was reported following the STROBE statement. The subjects were people over 65 years of age living in the community. Data collection included sociodemographic variables related to COVID-19, risk perception and types, coping styles in the face of contagion, sense of coherence, and preventive behaviors in the face of COVID-19. The data collection period was from November 2020 to January 2021. Results: A total of 305 people participated in this study (71.5% women, mean age 71.34 years; 6.9% suffered from COVID-19 and 44.3% knew someone close to them who suffered from the virus). The coping style variables problem-focused, emotion-focused, and sense of coherence subscales Significance and manageability explained 17% of the variable preventive behaviors against COVID-19. There were statistically significant differences by gender in all subscales, with women scoring higher in all of them; Conclusions: Men with low risk perception, extrinsic risk perception, and low sense of coherence presented worse COVID-19 preventive behaviors. It would be interesting to develop specific prevention and health education campaigns for this population.
Supervised Kohonen Self-Organizing Maps of Acute Asthma from Air Pollution Exposure
Authors: Kebalepile Moses Mogakolodi , Dzikiti Loveness Nyaradzo , Voyi Kuku
Published: October 2021

There are unanswered questions with regards to acute respiratory outcomes, particularly asthma, due to environmental exposures. In contribution to asthma research, the current study explored a computational intelligence paradigm of artificial neural networks (ANNs) called self-organizing maps (SOM). To train the SOM, air quality data (nitrogen dioxide, sulphur dioxide and particulate matter), interpolated to geocoded addresses of asthmatics, were used with clinical data to classify asthma outcomes. Socio-demographic data such as age, gender and race were also used to perform the classification by the SOM. All pollutants and demographic traits appeared to be important for the correct classification of asthma outcomes. Age was more important: older patients were more likely to have asthma. The resultant SOM model had low quantization error. The study concluded that Kohonen self-organizing maps provide effective classification models to study asthma outcomes, particularly when using multidimensional data. SO2 was concluded to be an important pollutant that requires strict regulation, particularly where frail subpopulations such as the elderly may be at risk.
Association between Participation in Counseling and Retention in a Buprenorphine-Assisted Treatment Program for People Experiencing Homelessness with Opioid Use Disorder
Authors: Berry Amanda R. W. , Finlayson Tracy L. , Mellis Luke M. , Urada Lianne A.
Published: October 2021

The opioid epidemic is a public health crisis that disproportionately affects our unsheltered neighbors. Because medication-assisted treatment (MAT) is effective for preventing deaths from drug overdose and retention is associated with better health outcomes, there is a clear need for more research on factors impacting retention in care. This retrospective cohort analysis examines the relationship between attendance in counseling and retention on buprenorphine for three or more months for individuals experiencing homelessness being treated at a Federally Qualified Health Center (FQHC) and Public Health Service Act §330(h) Health Care for the Homeless Program grantee in San Diego County, California. The cohort included 306 adults experiencing homelessness who had at least one prescription for buprenorphine and participated in a MAT program between 2017 and 2019. The sample included 64.4% men, almost exclusively white, and 35% lived in a place not meant for human habitation. Of the sample, 97 patients were retained at 3 months and 209 were not. Results from a logistic regression model showed that counseling appointments were positively associated with retention at three months (OR = 1.57, p < 0.001). Findings from this study inform future MAT program design components for people experiencing homelessness.
Status of Constipation and Its Association with Sarcopenia in Older Adults: A Population-Based Cohort Study
Authors: Park Hyungchul , Lim Jihye , Baek Ji Yeon , Lee Eunju , Jung Hee-Won , Jang Il-Young
Published: October 2021

(1) Background: As the clinical relevance of constipation and sarcopenia is not well studied, we aimed to investigate the association between them in older adults. (2) Methods: A cross-sectional study was conducted on 1278 community-dwelling older adults in South Korea. The Rome IV criteria were used to identify patients with clinically defined constipation, while sarcopenia was defined by the Asian Working Group for Sarcopenia consensus. The cohort was classified into three groups: no constipation, self-reported constipation only, and clinically defined constipation. (3) Results: The presence of constipation was associated with sarcopenia and slow gait speed (p < 0.001). After adjustment for possible covariates, the association with sarcopenia attenuated, while that for slow gait speed persisted. In terms of geriatric parameters, both groups with clinically defined and self-reported constipation had a higher burden of cognitive impairment, IADL disability, and lower QOL scores (p < 0.05) compared with those without constipation. (4) Conclusions: Sarcopenia and slow gait speed associated with constipation in community-dwelling older adults. Individuals with self-reported constipation symptoms alone showed comparable sarcopenic and geriatric burden to those with clinically defined constipation. Clinical suspicion for possible co-existing sarcopenia is warranted in older patients with constipation.
The HOME Study: Understanding How College Students at a Hispanic Serving Institution Coped with Food Insecurity in a Pandemic
Authors: Manboard Miriam , Johnson Cassandra M. , Thornton Hannah , Biediger-Friedman Lesli
Published: October 2021

College students represent a unique population of adults, who may be more likely to experience food insecurity due to their transient circumstances, limited access to resources, and increased educational expenses. But little is known about how college students and their households mitigate food insecurity, particularly during a crisis like the COVID-19 pandemic. The Household Observations of Meals and Environments (HOME) Study described how college students in the US utilized multilevel resources, including an on-campus food pantry, to maintain food security during the pandemic. A convenience sample of college students (n = 18) were recruited from an on-campus food pantry and provided quantitative and qualitative data through online surveys and in-depth Zoom interviews. Survey data were analyzed to describe sociodemographic characteristics. In-depth interviews were recorded, transcribed, coded, and analyzed thematically to identify emergent themes. Social support and the use of an on-campus food pantry were primary factors in maintaining a food security safety net. Students faced barriers when trying to access federal and state food assistance programs and identified multilevel resources, their food security, and the role of social support as facilitators in their perceptions of food insecurity status and experiences. Findings highlight practical implications for research related to on-campus food insecurity interventions and policies to support food security among college students.
Race, Ethnicity, Nativity and Perceptions of Health Risk during the COVID-19 Pandemic in the US
Authors: Jamieson Thomas , Caldwell Dakota , Gomez-Aguinaga Barbara , Doña-Reveco Cristián
Published: October 2021

Previous research demonstrates that pandemics, including COVID-19, have disproportionate effects on communities of color, further exacerbating existing healthcare inequities. While increasing evidence points to the greater threat posed by COVID-19 to Latinx communities, less remains known about how identification as Latinx and migration status influence their perception of risk and harm. In this article, we use cross-sectional data from a large national probability sample to demonstrate a large positive association between ethnic identity and migration status and perceptions of harm from COVID-19 in the US. We find that individuals identifying as Hispanic/Latinx and first-generation immigrants report significantly greater risks of becoming infected by COVID-19 in the next three months, and dying from the virus if they do contract it. Further, subgroup analysis reveals that health risks are especially felt by individuals of Mexican descent, who represent the largest share of US Latinxs. Collectively, our results provide evidence about how the pandemic places increased stress on people from Latinx and immigrant communities relative to White non-Hispanic individuals in the US.
Structural Analysis and Spatiotemporal Expression of Atxn1 Genes in Zebrafish Embryos and Larvae
Authors: Vauti Franz , Vögele Viktoria , Deppe Isabel , Hahnenstein Susanne T. , Köster Reinhard W.
Published: October 2021

Zebrafish have come into focus to model cerebellar diseases such as spinocerebellar ataxias (SCAs), which is caused by an expansion of translated CAG repeats in several unrelated genes. In spinocerebellar ataxia type 1 (SCA1), gain-of-function in the mutant ATXN1 contributes to SCA1’s neuropathy. Human ATXN1 and its paralog ATXN1L are chromatin-binding factors, act as transcriptional repressors, and have similar expression patterns. However, little is known about atxn1 genes in zebrafish. Recently, two family members, atxn1a and atxn1b, were identified as duplicate orthologs of ATXN1, as was atxn1l, the ortholog of ATXN1L. In this study, we analyzed the phylogenetic relationship of the atxn1 family members in zebrafish, compared their genetic structures, and verified the predicted transcripts by both RT-PCR and whole-mount in situ hybridization. All three genes, atxn1a, atxn1b, and atxn1l, show overlapping, but also distinct, expression domains during embryonic and larval development. While atxn1a and atxn1l display similar spatiotemporal embryonic expression, atxn1b expression is initiated during the onset of brain development and is predominantly expressed in the cerebellum throughout zebrafish development. These results provide new insights into atxn1 genes and their expression patterns in zebrafish during embryonic and late-larval development and may contribute importantly to future experiments in disease modeling of SCAs.
Activation of Hypoxia-Inducible Factor-1α Signaling Pathway Has the Protective Effect of Intervertebral Disc Degeneration
Authors: Kim Jin-Woo , An Hyun-Ju , Yeo HyunJeong , Jeong Yunhui , Lee HyeonHae , Lee Jusung , Nam Kisik , Lee Jongheon , Shin Dong-Eun , Lee Soonchul
Published: October 2021

Intervertebral discs (IVDs) have poor nutrient diffusion, because the nucleus pulposus (NP) lacks direct vascular supply and likely generates adenosine triphosphate by anaerobic glycolysis. Regulation of glycolysis is mediated by hypoxia-inducible factor-1α (HIF-1α), a transcription factor that responds to local oxygen tension. Constitutively active HIF-1α (CA HIF-1α) was created by point mutation and determined the protective role of HIF-1α in IVD degeneration. Under fluoroscopy, rat caudal IVD segments were stabbed by a needle puncture, and pcDNA3- HIF-1α wild-type (WT) or pcDNA3-CA HIF-1α was transfected into NP cell lines. The constitutive activity of CA HIF-1α was analyzed using a luciferase assay after cell lysis. Next, IVD tissue samples were retrieved from five patients with degenerative lumbar spinal stenosis at the time of surgery, and NP cells were cultured. NP cells were transfected with CA HIF-1α, and relevant gene expression was measured. HIF-1α protein levels in the nucleus were significantly higher, and transcriptional activity was 10.3-fold higher in NP cells with CA HIF-1α than in those with HIF-1α WT. Gene transfer of CA HIF-1α into NP cells enhanced the expression of Glut-1, Glut-3, aggrecan, type II collagen, and Sox9. Moreover, CA HIF-1α reduced the apoptosis of NP cells induced by the Fas ligand. The HIF-1α and collagen 2 expression levels were notably increased in the NP cells of the CA HIF-1α transfected segments in histology and immunohistochemistry study. Collectively, these results suggest that activation of HIF-1α signaling pathway may play a protective role against IVD degeneration and could be used as a future therapeutic agent.
Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway
Authors: Deng Jiaqiang , Ouyang Ping , Li Weiyao , Zhong Lijun , Gu Congwei , Shen Liuhong , Cao Suizhong , Yin Lizi , Ren Zhihua , Zuo Zhicai , Deng Junliang , Yan Qigui , Yu Shumin
Published: October 2021

Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene (Atg) 7 and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.
Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies
Authors: Popov Jelena , Caputi Valentina , Nandeesha Nandini , Rodriguez David Avelar , Pai Nikhil
Published: October 2021

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.
Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration
Authors: Damian Corina , Ghuman Harmanvir , Mauney Carrinton , Azar Reem , Reinartz Janina , Badylak Stephen F. , Modo Michel
Published: October 2021

Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14- and 28-days post-stroke were efficiently (80%) degraded by 14-days post-bioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14- and 28-days post-stroke but reduced in the 90-days post-stroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain.
Anti-Inflammatory Activities of Captopril and Diuretics on Macrophage Activity in Mouse Humoral Immune Response
Authors: Bryniarski Paweł , Nazimek Katarzyna , Marcinkiewicz Janusz
Published: October 2021

Hypertension is accompanied by the over-activation of macrophages. Diuretics administered alone or in combination with hypotensive drugs may have immunomodulatory effects. Thus, the influence of tested drugs on mouse macrophage-mediated humoral immunity was investigated. Mice were treated intraperitoneally with captopril (5 mg/kg) with or without hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) by 8 days. Mineral oil-induced peritoneal macrophages were harvested to assess the generation of cytokines in ELISA, and the expression of surface markers was analyzed cytometrically. Macrophages were also pulsed with sheep red blood cells (SRBC) and transferred to naive mice for evaluation of their ability to induce a humoral immune response. Tested drugs increase the expression of surface markers important for the antigen phagocytosis and presentation. SRBC-pulsed macrophages from mice treated with captopril combined with diuretics increased the secretion of antigen-specific antibodies by recipient B cells, while macrophages of mice treated with hydrochlorothiazide or furosemide with captopril increased the number of antigen-specific B cells. Tested drugs alter the macrophage secretory profile in favor of anti-inflammatory cytokines. Our results showed that diuretics with or without captopril modulate the humoral response by affecting the function of macrophages, which has significant translational potential in assessing the safety of antihypertensive therapy.
A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism
Authors: Thistlethwaite Sian , Jeffreys Laura N. , Girvan Hazel M. , McLean Kirsty J. , Munro Andrew W.
Published: October 2021

CYP102A1 (BM3) is a catalytically self-sufficient flavocytochrome fusion protein isolated from Bacillus megaterium, which displays similar metabolic capabilities to many drug-metabolizing human P450 isoforms. BM3′s high catalytic efficiency, ease of production and malleable active site makes the enzyme a desirable tool in the production of small molecule metabolites, especially for compounds that exhibit drug-like chemical properties. The engineering of select key residues within the BM3 active site vastly expands the catalytic repertoire, generating variants which can perform a range of modifications. This provides an attractive alternative route to the production of valuable compounds that are often laborious to synthesize via traditional organic means. Extensive studies have been conducted with the aim of engineering BM3 to expand metabolite production towards a comprehensive range of drug-like compounds, with many key examples found both in the literature and in the wider industrial bioproduction setting of desirable oxy-metabolite production by both wild-type BM3 and related variants. This review covers the past and current research on the engineering of BM3 to produce drug metabolites and highlights its crucial role in the future of biosynthetic pharmaceutical production.
Ultramicronized Palmitoylethanolamide in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation
Authors: D’Amico Ramona , Monaco Francesco , Siracusa Rosalba , Cordaro Marika , Fusco Roberta , Peritore Alessio Filippo , Gugliandolo Enrico , Crupi Rosalia , Cuzzocrea Salvatore , Di Paola Rosanna , Impellizzeri Daniela , Genovese Tiziana
Published: October 2021

Disseminated intravascular coagulation (DIC) is a severe condition characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. In the last years, it represents one of the most frequent consequences of coronavirus disease 2019 (COVID-19). The pathogenesis of DIC is complex, with cross-talk between the coagulant and inflammatory pathways. The objective of this study is to investigate the anti-inflammatory action of ultramicronized palmitoylethanolamide (um-PEA) in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by continual infusion of LPS (30 mg/kg) for 4 h through the tail vein. Um-PEA (30 mg/kg) was given orally 30 min before and 1 h after the start of intravenous infusion of LPS. Results showed that um-PEA reduced alteration of coagulation markers, as well as proinflammatory cytokine release in plasma and lung samples, induced by LPS infusion. Furthermore, um-PEA also has the effect of preventing the formation of fibrin deposition and lung damage. Moreover, um-PEA was able to reduce the number of mast cells (MCs) and the release of its serine proteases, which are also necessary for SARS-CoV-2 infection. These results suggest that um-PEA could be considered as a potential therapeutic approach in the management of DIC and in clinical implications associated to coagulopathy and lung dysfunction, such as COVID-19.
BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury
Authors: Ahn So Yoon , Sung Dong Kyung , Chang Yun Sil , Sung Se In , Kim Young Eun , Kim Hyo-Jin , Lee Soon Min , Park Won Soon
Published: October 2021

We investigated whether irradiated brain-derived neurotropic factor (BDNF)-overexpressing engineered human mesenchymal stem cells (BDNF-eMSCs) improve paracrine efficiency and, thus, the beneficial potency of naïve MSCs against severe hypoxic ischemic (HI) brain injury in newborn rats. Irradiated BDNF-eMSCs hyper-secreted BDNF > 10 fold and were >5 fold more effective than naïve MSCs in attenuating the oxygen-glucose deprivation-induced increase in cytotoxicity, oxidative stress, and cell death in vitro. Only the irradiated BDNF-eMSCs, but not naïve MSCs, showed significant attenuating effects on severe neonatal HI-induced short-term brain injury scores, long-term progress of brain infarct, increased apoptotic cell death, astrogliosis and inflammatory responses, and impaired negative geotaxis and rotarod tests in vivo. Our data, showing better paracrine potency and the resultant better therapeutic efficacy of the irradiated BDNF-eMSCs, compared to naïve MSCs, suggest that MSCs transfected with the BDNF gene might represent a better, new therapeutic strategy against severe neonatal HI brain injury.
Elevated Monocytic Interleukin-8 Expression under Intermittent Hypoxia Condition and in Obstructive Sleep Apnea Patients
Authors: Chuang Li-Pang , Wu Huang-Pin , Lee Li-Ang , Chiu Li-Chung , Lin Shih-Wei , Hu Han-Chung , Kao Kuo-Chin , Chen Ning-Hung , Tsai Jung-Wei , Pang Jong-Hwei Su
Published: October 2021

Obstructive sleep apnea (OSA) is a disease with great cardiovascular risk. Interleukin-8 (IL-8), an important chemokine for monocyte chemotactic migration, was studied under intermittent hypoxia condition and in OSA patients. Monocytic THP-1 cells were used to investigate the effect of intermittent hypoxia on the regulation of IL-8 by an intermittent hypoxic culture system. The secreted protein and mRNA levels were studied by means of enzyme-linked immunosorbent assay and RT/real-time PCR. The chemotactic migration of monocytes toward a conditioned medium containing IL-8 was performed by means of the transwell filter migration assay. Peripheral venous blood was collected from 31 adult OSA patients and RNA was extracted from the monocytes for the analysis of IL-8 expression. The result revealed that intermittent hypoxia enhanced the monocytic THP-1 cells to actively express IL-8 at both the secreted protein and mRNA levels, which subsequently increased the migration ability of monocytes toward IL-8. The ERK, PI3K and PKC pathways were demonstrated to contribute to the activation of IL-8 expression by intermittent hypoxia. In addition, increased monocytic IL-8 expression was found in OSA patients, with disease severity dependence and diurnal changes. This study concluded the monocytic IL-8 gene expression can be activated by intermittent hypoxia and increased in OSA patients.