bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender and Childhood Victimization: A Longitudinal Study of Heavy Drinking in Young Adulthood
Authors: Ash-Houchen William , Lo Celia C. , Gerling Heather M. , Cheng Tyrone C.
Published: October 2021

The present longitudinal study, for 12 years, followed a group of young adults, examining (1) whether/how victimization in childhood increased the likelihood of heavy drinking; (2) whether depression mediated the strain–heavy drinking relationship; and (3) whether/how relationships among strain, depression, and heavy drinking differed across two gender groups. Data came from the National Longitudinal Survey of Youth 1997 cohort, dating 2004–2015 (5 interview waves and 22,549 person-wave measurements total). We linked consumption of 5+ drinks (during the month prior) to four discrete measures of violent victimization, to one measure of stressful events, and to depression. We needed to consider repeat measures of the same variables over time, so we used generalized estimating equations (GEE) to analyze data. Depression was found to increase heavy drinking uniformly. Empirical evidence confirmed that in the strain–heavy drinking relationship, depression plays a minor mediating role. Gender moderated heavy drinking’s associations. Specifically, bullying in childhood raised risk for female respondents. The current strain was associated with a higher risk of heavy drinking among male respondents. Childhood victimization, as well as current life stress, play an important role in depression and heavy drinking. Future research should focus on the development of specific, targeted care to reduce heavy drinking’s harm and promote equity among Americans.
Differences in Perceived Risk of Contracting SARS-CoV-2 during and after the Lockdown in Sub-Saharan African Countries
Authors: Osuagwu Uchechukwu Levi , Timothy Chikasirimobi G , Langsi Raymond , Abu Emmanuel K , Goson Piwuna Christopher , Mashige Khathutshelo P , Ekpenyong Bernadine , Ovenseri-Ogbomo Godwin O , Miner Chundung Asabe , Oloruntoba Richard , Ishaya Tanko , Charwe Deborah Donald , Envuladu Esther Awazzi , Nwaeze Obinna , Agho Kingsley Emwinyore
Published: October 2021

This study investigated risk perception of contracting and dying of SARS-CoV-2 in sub-Sahara Africa during and after the lockdown periods. Two online surveys were conducted one year apart, with participants 18 years and above living in sub-Sahara Africa or the diaspora. Each survey took four weeks. The first survey was taken from 18 April to 16 May 2020, i.e., during the lockdown. The second survey was taken from 14 April to 14 May 2021, i.e., after the lockdown. A cross-sectional study using adopted and modified questionnaires for both surveys were distributed through online platforms. Question about risks perception of contracting and dying of SARS-CoV-2 were asked. The Helsinki declaration was applied, and ethical approvals were obtained. Total responses for both surveys, i.e., both during and after the lockdown, was 4605. The mean age was similar in both surveys (18–28 years). The mean risk perception scores were higher after lockdown by 3.59%. Factors associated with risk perception of COVID-19 were survey period, age group, region of residence, and occupation. Non-health care workers had a lower risk perception of COVID-19. This first comparative study on the level of risk perception of Africans during and after the lockdown shows that one in every three and every four persons in sub-Sahara Africa felt at high risk of contracting COVID-19 and thought they could die from contracting the same, respectively.
Formative Research to Design a Child-Friendly Latrine in Bangladesh
Authors: Huda Tarique Md. Nurul , Jahir Tania , Sarker Sushobhan , Yeasmin Farzana , Masud Abdullah Al , Sultana Jesmin , Das Jyoti Bhushan , Nizame Fosiul Alam , Leontsini Elli , Shoab Abul Kasham , Kwong Laura H. , Rahman Mahbubur , Luby Stephen P. , Winch Peter J.
Published: October 2021

In low- and middle-income countries, most latrines are not accessible to young children. We explored how to modify existing pit latrines to make them child friendly. We conducted four focus group discussions with mothers to explore barriers to child latrine use. We then enrolled 20 households with a child aged 3–7 years old to test six enabling technologies developed based on the identified barriers. Two to three weeks after installing the selected enabling technologies in each household, researchers conducted 19 in-depth interviews with caregivers to explore the technologies’ acceptance and feasibility. Common barriers included the discomfort of squatting on a large pan, fear of darkness, and fear of a slippery floor. Of the potential solutions, a ring to stabilize the child while squatting in the latrine was preferred by children and was affordable and available. A wooden board with a smaller hole than the usual pan reduced fears of falling and helped eliminate discomfort but was inconvenient to handle and clean. A transparent fiberglass roof tile was affordable, available, increased visibility, and kept the latrine floor dry. In conclusion, the fiberglass roof tile and stability ring were two affordable and locally available technologies that facilitated latrine use by children aged 3–7 years.
T1DMicro: A Clinical Risk Calculator for Type 1 Diabetes Related Microvascular Complications
Authors: Tran Paul Minh Huy , Kim Eileen , Tran Lynn Kim Hoang , Khaled Bin Satter , Hopkins Diane , Gardiner Melissa , Bryant Jennifer , Bernard Risa , Morgan John , Bode Bruce , Reed John Chip , She Jin-Xiong , Purohit Sharad
Published: October 2021

Development of complications in type 1 diabetes patients can be reduced by modifying risk factors. We used a cross-sectional cohort of 1646 patients diagnosed with type 1 diabetes (T1D) to develop a clinical risk score for diabetic peripheral neuropathy (DPN), autonomic neuropathy (AN), retinopathy (DR), and nephropathy (DN). Of these patients, 199 (12.1%) had DPN, 63 (3.8%) had AN, 244 (14.9%) had DR, and 88 (5.4%) had DN. We selected five variables to include in each of the four microvascular complications risk models: age, age of T1D diagnosis, duration of T1D, and average systolic blood pressure and HbA1C over the last three clinic visits. These variables were selected for their strong evidence of association with diabetic complications in the literature and because they are modifiable risk factors. We found the optimism-corrected R2 and Harrell’s C statistic were 0.39 and 0.87 for DPN, 0.24 and 0.86 for AN, 0.49 and 0.91 for DR, and 0.22 and 0.83 for DN, respectively. This tool was built to help inform patients of their current risk of microvascular complications and to motivate patients to control their HbA1c and systolic blood pressure in order to reduce their risk of these complications.
Psychological Factors, Leisure Activities, and Satisfaction during the COVID-19 Pandemic: A Cross-Sectional Study in Eleven Spanish-Speaking Countries
Authors: Hidalgo-Andrade Paula , Paz Clara , Hermosa-Bosano Carlos , García-Manglano Javier , Sádaba-Chalezquer Charo , López-Madrigal Claudia , Serrano Cecilia , Fernández-Zapico Aurelio
Published: October 2021

The COVID-19 pandemic has affected the lives of millions of people worldwide. This study aimed to analyze the effects of several psychological factors (self-esteem, self-control, and emotional stability) over lifestyle-related variables (time spent on leisure activities) and the levels of satisfaction (family, friends, work, and leisure satisfaction) experienced during the COVID-19 outbreak. Data for this article were retrieved as part of a cross-sectional international study conducted in eleven Spanish-speaking countries between March and September 2020. The analyses were conducted using the responses of 9500 persons (65.95% women, 34.05% men). Structural equation modeling was used to test the direct and indirect effects of the psychological variables on satisfaction variables mediated by the time engaged in leisure activities. Our model indicated that psychological factors significantly predicted the amount of time spent in leisure activities and satisfaction. Overall, results indicate that self-esteem is a relevant psychological factor to consider in the development of psychological interventions directed at promoting healthy lifestyles. Nevertheless, further research is needed to validate the direction of the associations found in this study.
Malaysia’s Health Systems Response to COVID-19
Authors: Ang Zen Yang , Cheah Kit Yee , Shakirah Md. Sharif , Fun Weng Hong , Anis-Syakira Jailani , Kong Yuke-Lin , Sararaks Sondi
Published: October 2021

This study aimed to highlight the COVID-19 response by the Ministry of Health (MOH) and the Government of Malaysia in order to share Malaysia’s lessons and to improve future pandemic preparedness. The team conducted a rapid review using publicly available information from MOH, PubMed, and World Health Organisation (WHO) Global Research on Coronavirus Disease Database to compile Malaysia’s responses during the COVID-19 pandemic. Measures taken between 31 December 2019 and 3 June 2020 were classified into domains as well as the pillars described in the WHO COVID-19 Strategic Preparedness and Response Plan (WHO SPRP). Malaysia’s response incorporated all pillars in the WHO SPRP and consisted of five domains, (i) whole-of-government, (ii) cordon sanitaire/lockdown, (iii) equity of access to services and supports, (iv) quarantine and isolation systems, and (v) legislation and enforcement. Some crucial measures taken were activation of a centralised multi-ministerial coordination council where MOH acted as an advisor, with collaboration from non-government organisations and private sectors which enabled an effective targeted screening approach, provision of subsidised COVID-19 treatment and screening, isolation or quarantine of all confirmed cases, close contacts and persons under investigation, with all strategies applied irrespective of citizenship. This was provided for by way of the Prevention and Control of Infectious Diseases Act 1988. A combination of these measures enabled the nation to contain the COVID-19 outbreak by the end of June 2020.
No Association between Metabolic Syndrome and Periodontitis in Korean Postmenopausal Women
Authors: Kim Jeong-In , Choi Choong-Ho , Chung Ki-Ho
Published: October 2021

This study aimed to determine the association between metabolic syndrome (MetS) and periodontitis in Korean postmenopausal women. The study selected 3320 menopause women (40–79-year-old) from those who participated in the seventh Korea National Health and Nutrition Survey (2016–2018). This association was determined using frequency and multiple logistic regression analyses. The prevalence of MetS in postmenopausal women was 33.2%, and among the MetS components, abdominal obesity showed a higher odds ratio of periodontitis by 1.36 (95% confidence interval (CI): 1.12–1.65; p < 0.05). The odds ratio for periodontitis was 1.34 times higher (95% CI: 1.12–1.60) in the MetS prevalence group with three or more MetS components (p < 0.05); however, after adjusting for demographic characteristics and health behavior variables, it was not statistically significant. Therefore, our results indicated that MetS has no association with periodontitis in postmenopausal women after adjusting for confounding variables.
An Analysis of Male and Female Managers’ Responses to Work Stress: Focused on the Case of South Korea
Authors: Roh Kyung-Ran , Kim Eun-Bee
Published: October 2021

This study aims to determine how work the stress of female and male managers in Korean companies influences their capabilities and career development behavior and analyzes how it affects their turnover intention. According to the analysis results determined using the panel data from the Korean Women’s Development Institute, first, work stress experienced by managers increases their turnover intentions regardless of gender. Secondly, more work stress decreases the development behavior of male mangers but strengthens the career development behavior of female managers. Thirdly, greater work stress decreases manager capabilities but strengthens the capabilities of female managers. Fourthly, career development behavior and capabilities as a mediator variable act differently according to gender on the relationship between work stress and turnover intention. We discussed the results of this study while considering the peculiarities of Korea, which has strong male-centered corporate culture, and presented theoretical and practical implications of the results of this study.
The Importance of Cardiorespiratory vs. Muscular Fitness in Reducing the Odds of Hypertension in War Veterans: A Population-Based Study
Authors: Kasović Mario , Štefan Lovro , Kalčik Zvonimir
Published: October 2021

Purpose: The purpose of the study was to examine separate and combined associations between cardiorespiratory fitness (CRF) and musculoskeletal fitness (MF) with hypertension. Methods: In this cross-sectional study, participants were 764 men and women aged 45–75 years, who were part of the Homeland War between 1990 to 1995 (33.5% women). CRF included the 2-min step test, while MF was consisted of push-ups in 30 s, chair-stands in 30 s and sit-ups in 30 s. The prevalence of hypertension was defined according to new American College of Cardiology and American Hearts Association Blood Pressure Guidelines for systolic and diastolic blood pressure of ≥130 mmHg and/or ≥80 mmHg. Results: In models adjusted for sex, age, fatness and fasting blood glucose, we found a graded inverse association between CRF and MF with hypertension. Less cardiorespiratory and muscular fit individuals were more likely to have hypertension. When CRF and MF were combined, individuals with high MF and low CRF, low MF and high CRF and low MF and CRF were 1.77, 2.15 and 7.09 more likely to have of hypertension. Conclusion: Both CRF and MF are associated with the prevalence of hypertension, while the magnitude of the associations between MF and hypertension was more pronounced.
Towards an Ideology-Free, Truly Mechanistic Health Psychology
Authors: Hommel Bernhard , Beste Christian
Published: October 2021

Efficient transfer of concepts and mechanistic insights from the cognitive to the health sciences and back requires a clear, objective description of the problem that this transfer ought to solve. Unfortunately, however, the actual descriptions are commonly penetrated with, and sometimes even motivated by, cultural norms and preferences, a problem that has colored scientific theorizing about behavioral control—the key concept for many psychological health interventions. We argue that ideologies have clouded our scientific thinking about mental health in two ways: by considering the societal utility of individuals and their behavior a key criterion for distinguishing between healthy and unhealthy people, and by dividing what actually seem to be continuous functions relating psychological and neurocognitive underpinnings to human behavior into binary, discrete categories that are then taken to define clinical phenomena. We suggest letting both traditions go and establish a health psychology that restrains from imposing societal values onto individuals, and then taking the fit between behavior and values to conceptualize unhealthiness. Instead, we promote a health psychology that reconstructs behavior that is considered to be problematic from well-understood mechanistic underpinnings of human behavior.
Bioprinting of Cartilage with Bioink Based on High-Concentration Collagen and Chondrocytes
Authors: Beketov Evgeny E. , Isaeva Elena V. , Yakovleva Nina D. , Demyashkin Grigory A. , Arguchinskaya Nadezhda V. , Kisel Anastas A. , Lagoda Tatiana S. , Malakhov Egor P. , Kharlov Valentin I. , Osidak Egor O. , Domogatsky Sergey P. , Ivanov Sergey A. , Shegay Petr V. , Kaprin Andrey D.
Published: October 2021

The study was aimed at the applicability of a bioink based on 4% collagen and chondrocytes for de novo cartilage formation. Extrusion-based bioprinting was used for the biofabrication. The printing parameters were tuned to obtain stable material flow. In vivo data proved the ability of the tested bioink to form a cartilage within five to six weeks after the subcutaneous scaffold implantation. Certain areas of cartilage formation were detected as early as in one week. The resulting cartilage tissue had a distinctive structure with groups of isogenic cells as well as a high content of glycosaminoglycans and type II collagen.
Auxin and Target of Rapamycin Spatiotemporally Regulate Root Organogenesis
Authors: Xie Xiulan , Wang Ying , Datla Raju , Ren Maozhi
Published: October 2021

The programs associated with embryonic roots (ERs), primary roots (PRs), lateral roots (LRs), and adventitious roots (ARs) play crucial roles in the growth and development of roots in plants. The root functions are involved in diverse processes such as water and nutrient absorption and their utilization, the storage of photosynthetic products, and stress tolerance. Hormones and signaling pathways play regulatory roles during root development. Among these, auxin is the most important hormone regulating root development. The target of rapamycin (TOR) signaling pathway has also been shown to play a key role in root developmental programs. In this article, the milestones and influential progress of studying crosstalk between auxin and TOR during the development of ERs, PRs, LRs and ARs, as well as their functional implications in root morphogenesis, development, and architecture, are systematically summarized and discussed.
Hepatocarcinogenesis Prevention by Pirfenidone Is PPARγ Mediated and Involves Modification of Nuclear NF-kB p65/p50 Ratio
Authors: Silva-Gomez Jorge Antonio , Galicia-Moreno Marina , Sandoval-Rodriguez Ana , Miranda-Roblero Hipolito Otoniel , Lucano-Landeros Silvia , Santos Arturo , Monroy-Ramirez Hugo Christian , Armendariz-Borunda Juan
Published: October 2021

Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis might modulate human HCC development. Pirfenidone (PFD) has shown anti-fibrotic and anti-inflammatory functions in both clinical and experimental studies. The aim of this study was to evaluate PPARγ expression and localization in samples of primary human tumors and assess PFD-effect in early phases of hepatocarcinogenic process. Human HCC tissue samples were obtained by surgical resection. Experimental hepatocarcinogenesis was induced in male Fischer-344 rats. TGF-β1 and α-SMA expression was evaluated as fibrosis markers. NF-kB cascade, TNFα, IL-6, and COX-2 expression and localization were evaluated as inflammation indicators. Caspase-3, p53, and PARP-1 were used as apoptosis markers, PCNA for proliferation. Finally, PPARα and PPARγ expression were evaluated to understand the effect of PFD on the activation of such pathways. PPARγ expression was predominantly localized in cytoplasm in human HCC tissue. PFD was effective to prevent histopathological damage and TGF-β1 and α-SMA overexpression in the experimental model. Anti-inflammatory effects of PFD correlate with diminished IKK and decrease in both IkB-phosphorylation/NF-kB p65 expression and p65-translocation into the nucleus. Pro-apoptotic PFD-induced effects are related with p53 expression, Caspase-3 p17 activation, and PARP-1-cleavage. In conclusion, PFD acts as a tumor suppressor by preventing fibrosis, reducing inflammation, and promoting apoptosis in MRHM.
Short Peptides Make a Big Difference: The Role of Botany-Derived AMPs in Disease Control and Protection of Human Health
Authors: Luo Xiumei , Wu Wenxian , Feng Li , Treves Haim , Ren Maozhi
Published: October 2021

Botany-derived antimicrobial peptides (BAMPs), a class of small, cysteine-rich peptides produced in plants, are an important component of the plant immune system. Both in vivo and in vitro experiments have demonstrated their powerful antimicrobial activity. Besides in plants, BAMPs have cross-kingdom applications in human health, with toxic and/or inhibitory effects against a variety of tumor cells and viruses. With their diverse molecular structures, broad-spectrum antimicrobial activity, multiple mechanisms of action, and low cytotoxicity, BAMPs provide ideal backbones for drug design, and are potential candidates for plant protection and disease treatment. Lots of original research has elucidated the properties and antimicrobial mechanisms of BAMPs, and characterized their surface receptors and in vivo targets in pathogens. In this paper, we review and introduce five kinds of representative BAMPs belonging to the pathogenesis-related protein family, dissect their antifungal, antiviral, and anticancer mechanisms, and forecast their prospects in agriculture and global human health. Through the deeper understanding of BAMPs, we provide novel insights for their applications in broad-spectrum and durable plant disease prevention and control, and an outlook on the use of BAMPs in anticancer and antiviral drug design.
Screening and Identification of Candidate GUN1-Interacting Proteins in Arabidopsis thaliana
Authors: Wang Linjuan , Huang Xingqi , Li Kui , Song Shuyuan , Jing Yunhe , Lu Shan
Published: October 2021

Chloroplasts are semi-autonomous organelles governed by the precise coordination between the genomes of their own and the nucleus for functioning correctly in response to developmental and environmental cues. Under stressed conditions, various plastid-to-nucleus retrograde signals are generated to regulate the expression of a large number of nuclear genes for acclimation. Among these retrograde signaling pathways, the chloroplast protein GENOMES UNCOUPLED 1 (GUN1) is the first component identified. However, in addition to integrating aberrant physiological signals when chloroplasts are challenged by stresses such as photooxidative damage or the inhibition of plastid gene expression, GUN1 was also found to regulate other developmental processes such as flowering. Several partner proteins have been found to interact with GUN1 and facilitate its different regulatory functions. In this study, we report 15 possible interacting proteins identified through yeast two-hybrid (Y2H) screening, among which 11 showed positive interactions by pair-wise Y2H assay. Through the bimolecular fluorescence complementation assay in Arabidopsis protoplasts, two candidate proteins with chloroplast localization, DJC31 and HCF145, were confirmed to interact with GUN1 in planta. Genes for these GUN1-interacting proteins showed different fluctuations in the WT and gun1 mutant under norflurazon and lincomycin treatments. Our results provide novel clues for a better understanding of molecular mechanisms underlying GUN1-mediated regulations.
NR4A3: A Key Nuclear Receptor in Vascular Biology, Cardiovascular Remodeling, and Beyond
Authors: Martínez-González José , Cañes Laia , Alonso Judith , Ballester-Servera Carme , Rodríguez-Sinovas Antonio , Corrales Irene , Rodríguez Cristina
Published: October 2021

The mechanisms committed in the activation and response of vascular and inflammatory immune cells play a major role in tissue remodeling in cardiovascular diseases (CVDs) such as atherosclerosis, pulmonary arterial hypertension, and abdominal aortic aneurysm. Cardiovascular remodeling entails interrelated cellular processes (proliferation, survival/apoptosis, inflammation, extracellular matrix (ECM) synthesis/degradation, redox homeostasis, etc.) coordinately regulated by a reduced number of transcription factors. Nuclear receptors of the subfamily 4 group A (NR4A) have recently emerged as key master genes in multiple cellular processes and vital functions of different organs, and have been involved in a variety of high-incidence human pathologies including atherosclerosis and other CVDs. This paper reviews the major findings involving NR4A3 (Neuron-derived Orphan Receptor 1, NOR-1) in the cardiovascular remodeling operating in these diseases.
Reconstitution of Monocyte Subsets and PD-L1 Expression but Not T Cell PD-1 Expression in Obstructive Sleep Apnea Patients upon PAP Therapy
Authors: Polasky Christina , Steffen Armin , Loyal Kristin , Lange Christian , Bruchhage Karl-Ludwig , Pries Ralph
Published: October 2021

Obstructive sleep apnea (OSA) is characterized by nocturnal breathing intermissions resulting in oxidative stress and eventually, a low-grade systemic inflammation. The study aimed to investigate the impact of positive airway pressure (PAP) therapy on the inflammatory milieu as measured by monocyte and T cell phenotypic alterations. Participants were assessed for their OSA severity before PAP therapy and about six months later, including patient-reported outcome and therapy usage by telemetry readout. The distributions of the CD14/CD16-characterized monocyte subsets as well as the CD4/CD8-characterized effector T cell subsets with regard to their PD-1 and PD-L1 expression were analyzed by flow cytometry from blood samples. Data of 25 patients revealed a significant reconstitution of the monocyte subset distribution and a decrease in PD-L1 expression on pan-monocytes and CD8+ T cells without an association to initial AHI and overweight. The PD-1 expression was still increased on T cell subsets, especially on CD4+ TH17/22 cells. We conclude that PAP therapy might have a rapid effect on the monocyte phenotype and overall PD-L1 expression levels. However, T cell immune alterations especially on TH17/22 cells persist longer, indicating an ongoing disturbance of the adaptive immune system.
Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery
Authors: Market Marisa , Tennakoon Gayashan , Auer Rebecca C.
Published: October 2021

Surgical resection is the foundation for the curative treatment of solid tumors. However, metastatic recurrence due to the difficulty in eradicating micrometastases remain a feared outcome. Paradoxically, despite the beneficial effects of surgical removal of the primary tumor, the physiological stress resulting from surgical trauma serves to promote cancer recurrence and metastasis. The postoperative environment suppresses critical anti-tumor immune effector cells, including Natural Killer (NK) cells. The literature suggests that NK cells are critical mediators in the formation of metastases immediately following surgery. The following review will highlight the mechanisms that promote the formation of micrometastases by directly or indirectly inducing NK cell suppression following surgery. These include tissue hypoxia, neuroendocrine activation, hypercoagulation, the pro-inflammatory phase, and the anti-inflammatory phase. Perioperative therapeutic strategies designed to prevent or reverse NK cell dysfunction will also be examined for their potential to improve cancer outcomes by preventing surgery-induced metastases.
Properties of Two Broad Host Range Phages of Yersinia enterocolitica Isolated from Wild Animals
Authors: Hammerl Jens A. , Barac Andrea , Erben Philipp , Fuhrmann Julius , Gadicherla Ashish , Kumsteller Franziska , Lauckner Anne , Müller Felix , Hertwig Stefan
Published: October 2021

Yersinia (Y.) enterocolitica and Y. pseudotuberculosis are important zoonotic agents which can infect both humans and animals. To combat these pathogens, the application of strictly lytic phages may be a promising tool. Since only few Yersinia phages have been described yet, some of which demonstrated a high specificity for certain serotypes, we isolated two phages from game animals and characterized them in terms of their morphology, host specificity, lytic activity on two bio-/serotypes and genome composition. The T7-related podovirus vB_YenP_Rambo and the myovirus vB_YenM_P281, which is very similar to a previously described phage PY100, showed a broad host range. Together, they lysed all the 62 tested pathogenic Y. enterocolitica strains belonging to the most important bio-/serotypes in Europe. A cocktail containing these two phages strongly reduced cultures of a bio-/serotype B4/O:3 and a B2/O:9 strain, even at very low MOIs (multiplicity of infection) and different temperatures, though, lysis of bio-/serotype B2/O:9 by vB_YenM_P281 and also by the related phage PY100 only occurred at 37 °C. Both phages were additionally able to lyse various Y. pseudotuberculosis strains at 28 °C and 37 °C, but only when the growth medium was supplemented with calcium and magnesium cations.
Mass Customized Outlook for Regenerative Heart Failure Care
Authors: Yamada Satsuki , Bartunek Jozef , Behfar Atta , Terzic Andre
Published: October 2021

Heart failure pathobiology is permissive to reparative intent. Regenerative therapies exemplify an emerging disruptive innovation aimed at achieving structural and functional organ restitution. However, mixed outcomes, complexity in use, and unsustainable cost have curtailed broader adoption, mandating the development of novel cardio-regenerative approaches. Lineage guidance offers a standardized path to customize stem cell fitness for therapy. A case in point is the molecular induction of the cardiopoiesis program in adult stem cells to yield cardiopoietic cell derivatives designed for heart failure treatment. Tested in early and advanced clinical trials in patients with ischemic heart failure, clinical grade cardiopoietic cells were safe and revealed therapeutic improvement within a window of treatment intensity and pre-treatment disease severity. With the prospect of mass customization, cardiopoietic guidance has been streamlined from the demanding, recombinant protein cocktail-based to a protein-free, messenger RNA-based single gene protocol to engineer affordable cardiac repair competent cells. Clinical trial biobanked stem cells enabled a systems biology deconvolution of the cardiopoietic cell secretome linked to therapeutic benefit, exposing a paracrine mode of action. Collectively, this new knowledge informs next generation regenerative therapeutics manufactured as engineered cellular or secretome mimicking cell-free platforms. Launching biotherapeutics tailored for optimal outcome and offered at mass production cost would contribute to advancing equitable regenerative care that addresses population health needs.
The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization
Authors: Liang Zhan-Ling , Tan Heng Wee , Wu Jia-Yi , Chen Xu-Li , Wang Xiu-Yun , Xu Yan-Ming , Lau Andy T. Y.
Published: October 2021

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.
Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis in Klebsiella pneumoniae Infection
Authors: Dong Guokai , Xu Nana , Wang Meng , Zhao Yunyun , Jiang Fei , Bu Huimin , Liu Jinjuan , Yuan Bo , Li Rongpeng
Published: October 2021

Given the rise of morbidity and mortality caused by Klebsiella pneumoniae (KP), the increasing number of strains resistant to antibiotics, and the emergence of hypervirulent Klebsiella pneumonia, treatment of KP infection becomes difficult; thus, novel drugs are necessary for treatment. Anthocyanins, or natural flavonoids, have an extensive effect against bacterial infection. However, few studies on anti-KP are identified. Here, we evaluated the therapeutic effect of purple sweet potato anthocyanins (PSPAs) on KP, containing 98.7% delphinidin 3-sambubioside. Results showed that KP-infected mice after PSPAs treatment manifested decreased mortality, weakened lung injury, dampened inflammatory responses, and reduced bacterial systemic dissemination in vivo. In Vitro, PSPAs significantly suppressed pyroptosis and restricted NLRP3 inflammasome activation in alveolar macrophages infected with KP. As for the mechanism, PSPAs promote mitophagy by recruiting Parkin to the mitochondria. PSPAs-conferred mitophagy increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species and mitochondrial DNA, resulting in impaired NLRP3 inflammasome activation. In addition, the promotion of mitophagy by PSPAs required the Nrf2 signaling pathway. Collectively, these findings suggest that PSPAs are a potential option for the treatment of KP infection.
Role of Orai3 in the Pathophysiology of Cancer
Authors: Sanchez-Collado Jose , Jardin Isaac , López Jose J. , Ronco Victor , Salido Gines M. , Dubois Charlotte , Prevarskaya Natalia , Rosado Juan A.
Published: October 2021

The mammalian exclusive Orai3 channel participates in the generation and/or modulation of two independent Ca2+ currents, the store-operated current, Icrac, involving functional interactions between the stromal interaction molecules (STIM), STIM1/STIM2, and Orai1/Orai2/Orai3, as well as the store-independent arachidonic acid (AA) (or leukotriene C4)-regulated current Iarc, which involves Orai1, Orai3 and STIM1. Overexpression of functional Orai3 has been described in different neoplastic cells and cancer tissue samples as compared to non-tumor cells or normal adjacent tissue. In these cells, Orai3 exhibits a cell-specific relevance in Ca2+ influx. In estrogen receptor-positive breast cancer cells and non-small cell lung cancer (NSCLC) cells store-operated Ca2+ entry (SOCE) is strongly dependent on Orai3 expression while in colorectal cancer and pancreatic adenocarcinoma cells Orai3 predominantly modulates SOCE. On the other hand, in prostate cancer cells Orai3 expression has been associated with the formation of Orai1/Orai3 heteromeric channels regulated by AA and reduction in SOCE, thus leading to enhanced proliferation. Orai3 overexpression is associated with supporting several cancer hallmarks, including cell cycle progression, proliferation, migration, and apoptosis resistance. This review summarizes the current knowledge concerning the functional role of Orai3 in the pathogenesis of cancer.
Can a Wastewater Treatment Plant Power Itself? Results from a Novel Biokinetic-Thermodynamic Analysis
Authors: Erguvan Mustafa , MacPhee David W.
Published: October 2021

The water–energy nexus (WEN) has become increasingly important due to differences in supply and demand of both commodities. At the center of the WEN is wastewater treatment plants (WWTP), which can consume a significant portion of total electricity usage in many developed countries. In this study, a novel multigeneration energy system has been developed to provide an energetically self-sufficient WWTP. This system consists of four major subsystems: an activated sludge process, an anerobic digester, a gas power (Brayton) cycle, and a steam power (Rankine) cycle. Furthermore, a novel secondary compressor has been attached to the Brayton cycle to power aeration in the activated sludge system in order to increase the efficiency of the overall system. The energy and exergy efficiencies have been investigated by varying several parameters in both WWTP and power cycles. The effect of these parameters (biological oxygen demand, dissolved oxygen level, turbine inlet temperature, compression ratio and preheater temperature) on the self-efficiency has also been investigated. It was found here that up to 109% of the wastewater treatment energy demand can be produced using the proposed system. The turbine inlet temperature of the Brayton cycle has the largest effect on self-sufficiency of the system. Energy and exergy efficiencies of the overall system varied from 35.7% to 46.0% and from 30.6% to 33.55%, respectively.
Reproductive, Obstetric and Neonatal Outcomes in Women with Congenital Uterine Anomalies: A Systematic Review and Meta-Analysis
Authors: Kim Min-A , Kim Hyo Sun , Kim Young-Han
Published: October 2021

Congenital uterine anomalies (CUA) may influence reproductive performance, resulting in adverse pregnancy associated complications. This study aimed to assess the association of CUA subtypes with reproductive, obstetric, and perinatal outcomes. We performed a systematic search of the MEDLINE, EMBASE, and Cochrane libraries for studies comparing pregnancy outcomes between women with CUA and those with a normal uterus. The random effects model was used to estimate the odds ratios (ORs) with a 95% confidence interval (CI). Women with CUA had a lower rate of live births (OR 0.47; 95% CI 0.33–0.69), and a higher rate of first trimester miscarriage (OR, 1.79; 95% CI 1.34–2.4), second trimester miscarriage (OR 2.92; 95% CI 1.35–6.32), preterm birth (OR 2.98; 95% CI 2.43–3.65), malpresentation (OR 9.1; 95% CI 5.88–14.08), cesarean section (OR 2.87; 95% CI 1.56–5.26), and placental abruption (OR 3.12; 95% CI 1.58–6.18). Women with canalization defects appear to have the poorest reproductive performance during early pregnancy. However, unification defects were associated with obstetric and neonatal outcomes throughout the course of pregnancy. It may be beneficial for clinicians to advise on potential complications that may be increased depending on the type and severity of CUA.
Interstitial Lung Disease in Connective Tissue Diseases: Survival Patterns in a Population-Based Cohort
Authors: Hyldgaard Charlotte , Bendstrup Elisabeth , Pedersen Alma Becic , Pedersen Lars , Ellingsen Torkell
Published: October 2021

Objectives: Interstitial lung disease (ILD) is associated with impaired survival among patients with connective tissue diseases (CTDs), but population-based data on the frequency of ILD and pulmonary hypertension (PH) in different CTD subtypes and the impact on survival are sparse. Methods: We included patients with a first-time ICD-10 diagnosis of systemic sclerosis (SSc), mixed connective tissue disease (MCTD), myositis, systemic lupus erythematosus (SLE), or Sjögren’s disease registered in the Danish National Patient Registry between 2000 and 2015. Among these, we identified patients with ILD and PH. Using Kaplan–Meier analysis, we assessed survival for the five subtypes of CTD ± ILD and compared survival among CTD patients overall ± ILD with survival in the general population ± ILD. Results: We identified 11,731 patients with a diagnosis of CTD; 637 (5.4%) had a diagnosis of ILD. The proportion of patients with ILD was higher in SSc (13.4%) and MCTD (9.1%) than in myositis (6.0%), SLE (4.1%), and Sjögren (2.8%). Fifty-one percent were diagnosed with ILD in their fifties and sixties. PH was more frequent in SSc (7.5%) and MCTD (4.1%). Five-year survival was 73.3% (66.7–80.6) in SSc-ILD, 81.0% (69.0–95.1) in MCTD-ILD, 84.7% (77.3–92.9) in myositis-ILD, 83.5% (76.2–91.5) in SLE-ILD, and 84.7 (78.4–91.6) in Sjögren-associated ILD. Survival in CTD-ILD overall was impaired for all age groups compared with CTD alone. Age-stratified survival was comparable between CTD-ILD and ILD in the general population. The survival gap between ILD and non-ILD increased with age. Conclusion: Survival was comparable between different CTD-ILD subtypes and comparable to survival in non-CTD-ILD.
Old and New Calcineurin Inhibitors in Lupus Nephritis
Authors: Ponticelli Claudio , Reggiani Francesco , Moroni Gabriella
Published: October 2021

Calcineurin inhibitors (CNIs) are drugs that inhibit calcineurin, a key phosphatase that dephosphorylates a transcription factor called the nuclear factor of activated T cells (NFAT), allowing its translocation into the nucleus of quiescent T cells. In the nucleus, NFAT activates interleukin 2, which stimulates the proliferation and differentiation of T-cells. CNIs can also stabilize the actin cytoskeleton of podocytes reducing proteinuria. Thanks to these characteristics, CNIs have been often used in the treatment of autoimmune diseases. However, the therapeutic index of CNIs is narrow, and their interactions with other drugs can increase toxicity or reduce efficacy. In lupus nephritis, cyclosporine and tacrolimus have been used both in induction and maintenance therapies. Observational studies and randomized controlled trials showed that both cyclosporine and tacrolimus can increase efficacy. Tolerance is satisfactory if low doses are used and the patient is carefully monitored. More recently, a new CNI, called voclosporin (VCS), has been approved by the Food and Drug Administration for use in lupus nephritis. VCS offers potential advantages over other CNIs. In two large multiethnic trials, VCS was not associated with adverse renal and metabolic events and obtained positive results despite a novel and rapid corticosteroid tapering regime.
An Evaluation of the Performance of Five Burnout Screening Tools: A Multicentre Study in Anaesthesiology, Intensive Care, and Ancillary Staff
Authors: Ong John , Lim Wan Yen , Doshi Kinjal , Zhou Man , Sng Ban Leong , Tan Li Hoon , Ong Sharon
Published: October 2021

Burnout is an important occupational hazard and early detection is paramount in preventing negative sequelae in physicians, patients, and healthcare systems. Several screening tools have been developed to replace lengthy diagnostic tools for large-scale screening, however, comprehensive head–to–head evaluation for performance and accuracy are lacking. The primary objective of this study was to compare the diagnostic performance of five burnout screening tools, including a novel rapid burnout screening tool (RBST). This was a cross-sectional study involving 493 hospital staff (anaesthesiology and intensive care doctors, nurses, and ancillary staff) at the COVID-19 frontline across four hospitals in Singapore between December 2020 and April 2021. The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was used as the reference standard. Five burnout screening tools, the single-item MBI measure of burnout (SI-MBI), dual-item MBI (DI-MBI), abbreviated MBI (aMBI), Single Item Burnout Question (SIBOQ), and the RBST, were administered via a 36-item online survey. Tools were administered simultaneously and responses were anonymised. Burnout prevalence was 19.9%. The RBST and the SI-MBI had the two highest accuracies (87.8% and 81.9% respectively) and AUROC scores (0.86, 95% CI: 0.83–0.89 and 0.86, 95% CI: 0.82–0.89 respectively). However, the accuracy of the RBST was significantly higher than the SI-MBI (p < 0.0001), and it had the highest positive likelihood ratio (+LR = 7.59, 95% CI 5.65–10.21). Brief screening tools detect burnout albeit with a wide range of accuracy. This can strain support services and resources. The RBST is a free screening tool that can detect burnout with a high degree of accuracy.
The Combination of Albumin–Bilirubin Score and Prothrombin Time Is a Useful Tool for Predicting Liver Dysfunction after Transcatheter Arterial Chemoembolization in Child–Pugh Class A Patients with Hepatocellular Carcinoma within Up-to-Seven Criteria
Authors: Takaya Hiroaki , Namisaki Tadashi , Takeda Soichi , Kaji Kosuke , Ogawa Hiroyuki , Ishida Koji , Tsuji Yuki , Takagi Hirotetsu , Ozutsumi Takahiro , Fujinaga Yukihisa , Furukawa Masanori , Kitagawa Koh , Nishimura Norihisa , Sawada Yasuhiko , Shimozato Naotaka , Kawaratani Hideto , Moriya Kei , Akahane Takemi , Mitoro Akira , Yoshiji Hitoshi
Published: October 2021

Mortality and recurrence rates of hepatocellular carcinoma (HCC) are high. Recent studies show that for patients with HCC beyond up-to-seven criteria, treatment with molecular-targeted agents (MTAs) is recommended because the treatment efficiency of transcatheter arterial chemoembolization (TACE) is poor; further, TACE increases decline in liver function. However, the relationship between TACE and liver function decline in patients with HCC within up-to-seven criteria has not been clarified. Hence, we aimed to investigate this relationship. This retrospective observational study included 189 HCC tumors within up-to-seven criteria in 114 Child–Pugh class A patients. Twenty-four (12.7%) tumors were changed from Child–Pugh class A to B after TACE, and 116 (61.4%) tumors exhibited recurrence within 6 months after TACE. Prothrombin time (PT) and albumin–bilirubin (ALBI) score before TACE were significantly associated with liver dysfunction from Child–Pugh class A to B. The combination of PT and ALBI score before TACE had high predictive ability for liver dysfunction from Child–Pugh class A to B after TACE (specificity = 100%, sensitivity = 91.7%). The combined use of pre-TACE PT and ALBI score has a high predictive ability for liver dysfunction after TACE for Child–Pugh class A patients with HCC within up-to-seven criteria.
Extracorporeal Membrane Oxygenation for COVID 2019-Acute Respiratory Distress Syndrome: Comparison between First and Second Waves (Stage 2)
Authors: Dognon Nicolas , Gaudet Alexandre , Parmentier-Decrucq Erika , Normandin Sylvain , Vincentelli André , Moussa Mouhamed , Poissy Julien , Duburcq Thibault ,   Lille Intensive Care COVID-19 Group
Published: October 2021

We aimed to compare the outcomes of patients under veno-venous extracorporeal membrane oxygenation (V-V ECMO) for COVID-19-Acute Respiratory Distress Syndrome (CARDS) between the first and the second wave. From 1 March 2020 to 30 November 2020, fifty patients requiring a V-V ECMO support for CARDS were included. Patient demographics, pre-ECMO, and day one, three, and seven on-ECMO data and outcomes were collected. The 90-day mortality was 11% higher during the second wave (18/26 (69%)) compared to the first wave (14/24 (58%) (p = 0.423). During the second wave, all of the patients were given steroids compared to 16.7% during the first wave (p < 0.001). The second wave’s patients had been on non-invasive ventilation support for a longer period than in the first wave, with the median time from ICU admission to ECMO implantation being significantly higher (14 (11–20) vs. 7.7 (5–12) days; p < 0.001). Mechanical properties of the lung were worsened in the second wave’s CARDS patients before ECMO implantation (median static compliance 20 (16–26) vs. 29 (25–37) mL/cmH2O; p < 0.001) and during ECMO days one, three, and seven. More bacterial co-infections before implantation and under ECMO were documented in the second wave group. Despite a better evidence-driven critical care management, we depicted fewer encouraging outcomes during the second wave.