bluuebunny/crossref_metadata_2025 huggingface dataset:
“No One Manages It; We Just Sign Them Up and Do It”: A Whole System Analysis of Access to Healthcare in One Remote Australian Community
Authors: Osborn Eloise , Ritha Marida , Macniven Rona , Agius Tim , Christie Vita , Finlayson Heather , Gwynn Josephine , Hunter Kate , Martin Robyn , Moir Rachael , Taylor Donna , Tobin Susannah , Ward Katrina , Gwynne Kylie
Published: March 2022

Objective: To assess the accessibility, availability and utilisation of a comprehensive range of community-based healthcare services for Aboriginal people and describe contributing factors to providing effective healthcare services from the provider perspective. Setting: A remote community in New South Wales, Australia. Participants: Aboriginal and non-Aboriginal health and education professionals performing various roles in healthcare provision in the community. Design: Case study. Methodology: The study was co-designed with the community. A mixed-methods methodology was utilised. Data were gathered through structured interviews. Descriptive statistics were used to analyse the availability of 40 health services in the community, whilst quotations from the qualitative research were used to provide context for the quantitative findings. Results: Service availability was mapped for 40 primary, specialised, and allied health services. Three key themes emerged from the analysis: (1) there are instances of both underservicing and overservicing which give insight into systemic barriers to interagency cooperation; (2) nurses, community health workers, Aboriginal health workers, teachers, and administration staff have an invaluable role in healthcare and improving patient access to health services and could be better supported through further funding and opportunities for specialised training; and (3) visiting and telehealth services are critical components of the system that must be linked to existing community-led primary care services. Conclusion: The study identified factors influencing service availability, accessibility and interagency cooperation in remote healthcare services and systems that can be used to guide future service and system planning and resourcing.
Prevalence of Obesity and Associated Risk Factors among Children and Adolescents in the Eastern Cape Province
Authors: Nomatshila Sibusiso , Mabunda Sikhumbuzo , Puoane Thandi , Apalata Teke
Published: March 2022

Obesity is a global public health concern that begins in childhood and is on the rise among people aged 18 and up, with substantial health consequences that offer socioeconomic challenges at all levels, from households to governments. Obesity and associated risk factors were investigated in children and adolescents in the Eastern Cape Province of South Africa. A cross-sectional study was conducted at Mt Frere among 209 conveniently selected participants using anthropometric measurements and a structured questionnaire. Chi-squared statistics or Fisher’s exact test were used to evaluate the risk factors predicting different outcomes such as hypertension or diabetes mellitus. A 5% level of significance was used for statistical significance (p-value 0.05). The prevalence of overweight or obesity among females when using waist circumference (2.7%), triceps skinfold (6.9%), and body mass index cut-offs (16.4%) were respectively higher when compared to those of males. About 89% engaged in physical activities. After school, 53% watched television. About 24.9% of participants did not eat breakfast. Most of overweight or obese participants (92.9%) brought pocket money to school. Use of single anthropometric measurements for assessing nutritional status indicated inconclusive results. Strengthening parental care, motivation for consumption of breakfast and limiting pocket money for children going to school are important steps to improve child health.
Cardiometabolic Health Status, Ethnicity and Health-Related Quality of Life (HRQoL) Disparities in an Adult Population: NutrIMDEA Observational Web-Based Study
Authors: Ribot-Rodriguez Rosa , Higuera-Gomez Andrea , San-Cristobal Rodrigo , Martín-Hernández Roberto , Micó Víctor , Espinosa-Salinas Isabel , Ramírez de Molina Ana , Martínez J. Alfredo
Published: March 2022

Precision public health supported on online tools is increasingly emerging as a potential strategy to achieve health promotion and disease prevention. Our aim was to assess the relationships of sociodemographic variables, anthropometric data, dietary habits and lifestyle factors with health-related quality of life (HRQoL), cardiometabolic health status and ethnicity in an online recruited adult population (NutrIMDEA Study). NutrIMDEA Study is a web-based cross-sectional survey that included 17,333 adults. Self-reported sociodemographic characteristics, anthropometric data, clinical and family history of cardiometabolic illnesses, dietary habits, lifestyle factors and HRQoL features were collected. Diseased individuals showed significative poorer MedDiet and worse HRQoL than those in the healthy cardiometabolic status group (p < 0.05). In comparison, European/Caucasian individuals reported a significantly better HRQoL, higher MedDiet and HRQoL values compared with those of other ethnicities (p < 0.05). We obtained a total of 16.8% who reported poor/fair, 56.5% good and 26.6% very good/excellent HRQoL. Respondents with very good/excellent HRQoL showed lower BMI, greater adherence to a Mediterranean diet (MedDiet) and higher physical activity. The results suggest the presence of interactions between the mental and physical components of HRQoL with obesity, sedentarism and dietary intake, which were dependent on disease status and ethnicity. Online HRQoL assessment could contribute to wider implementation of precision public health strategies to promote health targeted interventions with policy implications to community health promotion.
Assessment of Quality of Life in Men Treated for Infertility in Poland
Authors: Makara-Studzińska Marta , Limanin Agnieszka , Anusiewicz Agnieszka , Janczyk Paula , Raczkiewicz Dorota , Wdowiak-Filip Anita , Filip Michał , Bojar Iwona , Lukaszuk Krzysztof , Wdowiak Artur
Published: March 2022

The aim of this study was to assess the quality of life (QoL) of men treated for infertility in Poland. This cross-sectional study was conducted using the Abbreviated World Health Organization Quality of Life questionnaire (WHOQoL-BREF), Fertility Quality of Life tool (FertiQoL) and an author-constructed questionnaire. The study included 1200 men treated for infertility without the use of assisted reproductive technology (non-ART), intrauterine insemination (IUI) and in vitro fertilization (IVF). The control group consisted of 100 healthy men with confirmed fertility. The quality of life assessed by the WHOQoL-BREF questionnaire was significantly lower in study groups in the Environmental domain, compared to the control group (p = 0.009). Statistically significant differences were found in the case of FertiQoL subscales: Emotional, Mind-Body, Relational, and Treatment Environment, depending on applied treatment. Men whose partners were treated without the use of ART assessed their QoL significantly more negatively than those treated with IUI. Reproductive problems and type of their treatment influenced the quality of life of the affected men. Non-ART treatment, rural place of residence, and increased BMI were associated with lower QoL.
The Use of Virtual and Computational Technologies in the Psychomotor and Cognitive Development of Children with Down Syndrome: A Systematic Literature Review
Authors: Boato Elvio , Melo Geiziane , Filho Mário , Moresi Eduardo , Lourenço Carla , Tristão Rosana
Published: March 2022

Individuals with Down syndrome (DS) have numerous comorbidities due to trisomy 21. However, virtual reality-based therapy (VRT) has been used nowadays as a learning and visual motor tool in order to facilitate the development and learning process of this group. The aim of this article was to carry out an integrative review of the literature on the use of virtual and computational technologies in the stimulation of children with DS. A search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through single key words or their combinations using AND or OR operators: “Down syndrome” AND (“development” OR “cognition” OR “visomotor” OR “digital game” OR “virtual reality”). Eventually, 18 articles were included in our review. The games used in the research were able to stimulate, through the visual field, global motor skills, balance, body scheme and spatial organization, in addition to the learning of mathematical concepts, in order to directly influence the autonomous life activities, language skills, social skills and educational aspects of people with DS. Electronic games contribute to the teaching-learning relationship and stimulate neuropsychomotor and cognitive functions and development in children with DS.
Development of Teacher Rating Scale of Risky Play for 3- to 6-Year-Old Pre-Schoolers in Anji Play Kindergartens of East China
Authors: Lin Wenqi , Wu Jianfen , Wu Yunpeng , He Hongli
Published: March 2022

To help teachers better evaluate the level of risky play for pre-schoolers, the present study aimed to develop a Teacher Rating Scale of Risky Play (TRSRP) for 3–6 years Chinese Pre-schoolers. The scale was administered to a pre-schooler sample consisting of 1376 children (Mage = 57.53 months, SD = 10.38; 54.30% boys; 44.80% only child) recruited from Anji play kindergartens in Hangzhou, China. The psychometric properties of the instrument were examined. The reliability of scale was reported by calculating internal consistency. The construct validity of the scale was investigated by exploratory factor analysis and confirmatory factor analysis. The final 7-item measure was structured into two subscales: play with great heights and play with high speed. The results suggested that the TRSRP has acceptable internal consistency and construct validity and can be used as an effective tool to measure the level of risky play for 3–6 years pre-schoolers in China’s Anji play kindergartens.
A Scoping Review on the Epidemiology of Chronic Low Back Pain among Adults in Sub-Saharan Africa
Authors: Kahere Morris , Hlongwa Mbuzeleni , Ginindza Themba G.
Published: March 2022

Background: The global burden of chronic low back pain (CLBP) is a major concern in public health. Several CLBP epidemiological studies have been conducted in high-income-countries (HICs) with little known in low-and-middle-income-countries (LMICs) due to other competing priorities of communicable diseases. The extrapolation of results of studies from HICs for use in LMICs is difficult due to differences in social norms, healthcare systems, and legislations, yet there is urgent need to address this growing burden. It is against this backdrop that we conducted this review to map the current evidence on the distribution of CLBP in Sub-Saharan Africa (SSA). Methods: A comprehensive literature search was conducted from the following databases: PubMed, Google Scholar, Science Direct databases, World Health Organizations library databases, EMBASE, EBSCOhost by searching the following databases within the platform; academic search complete, CINAHL with full text, health sources: nursing/academic and MEDLINE. The title, abstract and the full text screening phases were performed by two independent reviewers with the third reviewer employed to adjudicate discrepancies. The reference list of all included articles was also searched for eligible articles. This scoping review was reported in accordance with the PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation, as well as guided by Arksey and O’Malley’s scoping review framework. A thematic content analysis was used to give a narrative account of the review. Results: The electronic search strategy retrieved 21,189 articles. Title/abstract and full text screening only identified 11 articles, which were included in this review. The prevalence of CLBP among the general population ranged from 18.1% to 28.2% and from 22.2% to 59.1% among LBP patients. The prevalence of occupation based CLBP ranged from 30.1% to 55.5%. Identified risk factors for CLBP are multifactorial and included biomechanical, psychological, socioeconomic and lifestyle factors, with psychosocial factors playing a significant role. Hypertension, diabetes mellitus, peptic ulcer disease were the most common comorbidities identified. CLBP disability was significantly associated with psychosocial factors. The management of CLBP in primary care follows the traditional biomedical paradigm and primarily involves pain medication and inconsistent with guidelines. Conclusions: There are limited epidemiological data on CLBP in SSA, however, this study concluded that the prevalence and risk factors of CLBP in SSA are comparable to reports in HICs. Considering the projected increase in the burden of CLBP in LMICs extensive research effort is needed to close this knowledge gap.
Sociodemographic Patterns of Exclusive and Dual Combustible Tobacco and E-Cigarette Use among US Adolescents—A Nationally Representative Study (2017–2020)
Authors: Usidame Bukola , Hirschtick Jana L. , Mattingly Delvon T. , Patel Akash , Patrick Megan E. , Fleischer Nancy L.
Published: March 2022

This study assessed the sociodemographic predictors of exclusive and dual use of the most frequently used nicotine/tobacco products, e-cigarettes, and combustible tobacco among adolescents. Cross-sectional data was from the 2017–2020 Monitoring the Future nationally representative study of eighth, tenth, and twelfth-grade students. We coded past 30 day nicotine/tobacco use into four mutually exclusive categories: no use, e-cigarette use only, combustible use (cigarette or cigar) only, and dual use (e-cigarette and combustible). We pooled the 2017–2020 data to examine the relationship between sex, race/ethnicity, parental education, and each product-use category using multinomial logistic regression, stratified by grade level. Among eighth (N = 11,189), tenth (N = 12,882), and twelfth graders (N = 11,385), exclusive e-cigarette use was the most prevalent pattern (6.4%, 13.2%, 13.8%, respectively), followed by dual use (2.7%, 4.5%, 8.9%), and exclusive combustible use (1.5%, 2.5%, 5.3%). eighth and tenth-grade adolescents whose highest parental education was a 4-year college degree or more had lower odds of exclusive combustible and dual use when compared to adolescents whose highest parental education was less than a high school degree. Research should continue to monitor the differential use of combustible tobacco products and e-cigarettes among adolescents from low socioeconomic status backgrounds or racial/ethnic minority households to inform ongoing and future interventions or policies.
The Impact of Online Learning on Physical and Mental Health in University Students during the COVID-19 Pandemic
Authors: Chu Yu-Hsiu , Li Yao-Chuen
Published: March 2022

Higher education organizations have been influenced by the COVID-19 pandemic. During school closures, online teaching and learning has become a new routine that may lead to changes in lifestyles and adversely affect university students’ health. Therefore, this study was to understand the potential impact of online learning on physical and mental health by investigating the differences in physical activity, psychological distress, and student life stress in Taiwanese university students between the in-class learning and online learning periods. A total of 181 students were recruited from a local university. All participants were requested to complete an online survey and self-report physical activity, psychological distress, and life stress in the in-class learning and online learning periods, respectively. The results indicated a significant reduction in physical activity of various intensities (p < 0.05). Specifically, male university students showed a greater decrease in vigorous physical activity compared to their female peers. Yet, there was no significant increase in psychological distress and life stress from the in-class learning period to the online learning period. In summary, physical activity drastically reduces during the online learning period in Taiwanese university students. Notably, male students may be at greater risk of insufficient participation in vigorous physical activity.
Can El Niño–Southern Oscillation Increase Respiratory Infectious Diseases in China? An Empirical Study of 31 Provinces
Authors: Tang Qingyun , Gong Ke , Xiong Li , Dong Yuanxiang , Xu Wei
Published: March 2022

Respiratory infectious diseases (RID) are the major form of infectious diseases in China, and are highly susceptible to climatic conditions. Current research mainly focuses on the impact of weather on RID, but there is a lack of research on the effect of El Niño–Southern Oscillation (ENSO) on RID. Therefore, this paper uses the system generalized method of moments (SYS-GMM) and the data of 31 provinces in China from 2007 to 2018 to construct a dynamic panel model to empirically test the causality between ENSO and RID morbidity. Moreover, this paper considers the moderating effects of per capita disposable income and average years of education on this causality. The results show that ENSO can positively and significantly impact RID morbidity, which is 5.842% higher during El Niño years than normal years. In addition, per capita disposable income and average years of education can effectively weaken the relationship between ENSO and RID morbidity. Thus, this paper is of great significance for improving the RID early climate warning system in China and effectively controlling the spread of RID.
The Influence of Economic Factors on the Relationship between Partnership Status and Health: A Gender Approach to the Spanish Case
Authors: Gumà-Lao Jordi
Published: March 2022

This study explores the relevance of economic factors (e.g., a household’s economic capacity and the prevailing economic context) to understand the relationship between the partnership status and the health of Spanish adult women and men (age 30–59). To do so, it draws on cross-sectional data from the Spanish sample of the European Union Statistics on Income and Living Conditions (EU-SILC) for the years 2005, 2010, and 2015 (i.e., before, during, and after the 2008–2012 economic recession). The results reveal dissimilar patterns of association between partnership status and both the health of, and the economic difficulties faced by Spanish women and men in each of the three years studied. Most notably, the partnership status of Spanish women has a greater impact on their likelihood of experiencing economic difficulties and poor health than does that of their male counterparts. Additionally, women are also more likely to experience economic difficulties during and after the economic recession. The disadvantageous situation of Spanish women in the public sphere is shown to have a negative impact on their ability to cope with the economic difficulties associated with the end of a union and a contextual recession.
Quantifying the Impact of Urban Form and Socio-Economic Development on China’s Carbon Emissions
Authors: Huang Cheng , Qu Yang , Huang Lingfang , Meng Xing , Chen Yulong , Pan Ping
Published: March 2022

Carbon emissions (CEs) are one of the most important factors causing global warming. The development of social economy and the acceleration of the urbanization process leads to increasing CEs, especially in China. Therefore, it has become an international community consensus to control the growth of CEs and mitigate global warming. Understanding the changing patterns and driving forces of CEs are important prerequisites for formulating policies that target the reduction of CEs in response to global warming. This study developed an improved logarithmic mean Divisia index (Spatial-LMDI) to explore the urban form and socio-economic driving forces of CEs in China. Comparing with previous studies, this study is unique in the way of applying spatial landscape index to LMDI decomposition analysis. The results show that population, per capita GDP, investment intensity and urban expansion are the top driving forces of CEs growth from 1995 to 2019. Investment efficiency, technology level, and aggregation are the most important factors in terms of restraining the growth of CEs. To achieve the goal of energy saving, CEs reduction and climate change mitigation, we proposed that strategies should be formulated as follows: improving efficiency of energy investment, optimizing the spatial distribution of construction land aggregation, and rationalizing distribution of industries.
Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP
Authors: Hong Yeon-Mi , Min Seo Yeon , Kim Dayeong , Kim Subin , Seo Daekwan , Lee Kyoung Hwa , Han Sang Hoon
Published: March 2022

Attenuating the expression of immediate early (IE) proteins is essential for controlling the lytic replication of human cytomegalovirus (HCMV). The human microRNAs (hsa-miRs), miR-200b-3p and miR-200c-3p, have been identified to bind the 3′-untranslated region (3′-UTR) of the mRNA encoding IE proteins. However, whether hsa-miRs can reduce IE72 expression and HCMV viral load or exhibit a crosstalk with the host cellular signaling machinery, most importantly the NF-κB cascade, has not been evaluated. In this study, argonaute-crosslinking and immunoprecipitation-seq revealed that miR-200b-3p and miR-200c-3p bind the 3′-UTR of UL123, which is a gene that encodes IE72. The binding of these miRNAs to the 3′-UTR of UL123 was verified in transfected cells stably expressing GFP. We used miR-200b-3p/miR-200c-3p mimics to counteract the downregulation of these miRNA after acute HCMV infection. This resulted in reduced IE72/IE86 expression and HCMV VL during lytic infection. We determined that IE72/IE86 alone can inhibit the phosphorylation of RelA/p65 at the Ser536 residue and that p-Ser536 RelA/p65 binds to the major IE promoter/enhancer (MIEP). The upregulation of miR-200b-3p and miR-200c-3p resulted in the phosphorylation of RelA/p65 at Ser536 through the downregulation of IE, and the binding of the resultant p-Ser536 RelA/p65 to MIEP resulted in a decreased production of pro-inflammatory cytokines. Overall, miR-200b-3p and miR-200c-3p—together with p-Ser536 RelA/p65—can prevent lytic HCMV replication during acute and latent infection.
Polyamines Metabolism Interacts with γ-Aminobutyric Acid, Proline and Nitrogen Metabolisms to Affect Drought Tolerance of Creeping Bentgrass
Authors: Tan Meng , Hassan Muhammad Jawad , Peng Yan , Feng Guangyan , Huang Linkai , Liu Lin , Liu Wei , Han Liebao , Li Zhou
Published: March 2022

Due to increased global warming and climate change, drought has become a serious threat to horticultural crop cultivation and management. The purpose of this study was to investigate the effect of spermine (Spm) pretreatment on metabolic alterations of polyamine (PAs), γ-aminobutyric acid (GABA), proline (Pro), and nitrogen associated with drought tolerance in creeping bentgrass (Agrostis stolonifera). The results showed that drought tolerance of creeping bentgrass could be significantly improved by the Spm pretreatment, as demonstrated by the maintenance of less chlorophyll loss and higher photosynthesis, gas exchange, water use efficiency, and cell membrane stability. The Spm pretreatment further increased drought-induced accumulation of endogenous PAs, putrescine, spermidine, and Spm, and also enhanced PAs metabolism through improving arginine decarboxylases, ornithine decarboxylase, S-adenosylmethionine decarboxylase, and polyamine oxidase activities during drought stress. In addition, the Spm application not only significantly improved endogenous GABA content, glutamate content, activities of glutamate decarboxylase and α-ketoglutarase, but also alleviated decline in nitrite nitrogen content, nitrate reductase, glutamine synthetase, glutamate synthetase, and GABA aminotransferase activities under drought stress. The Spm-pretreated creeping bentgrass exhibited significantly lower ammonia nitrogen content and nitrite reductase activity as well as higher glutamate dehydrogenase activity than non-pretreated plants in response to drought stress. These results indicated beneficial roles of the Spm on regulating GABA and nitrogen metabolism contributing towards better maintenance of Tricarboxylic acid (TCA) cycle in creeping bentgrass. Interestingly, the Spm-enhanced Pro metabolism rather than more Pro accumulation could be the key regulatory mechanism for drought tolerance in creeping bentgrass. Current findings provide a comprehensive understanding of PAs interaction with other metabolic pathways to regulate drought tolerance in grass species.
Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences
Authors: Boulahtouf Zakaria , Virzì Alessia , Baumert Thomas F. , Verrier Eloi R. , Lupberger Joachim
Published: March 2022

Chronic viral hepatitis is a main cause of liver disease and hepatocellular carcinoma. There are striking similarities in the pathological impact of hepatitis B, C, and D, although these diseases are caused by very different viruses. Paired with the conventional study of protein–host interactions, the rapid technological development of -omics and bioinformatics has allowed highlighting the important role of signaling networks in viral pathogenesis. In this review, we provide an integrated look on the three major viruses associated with chronic viral hepatitis in patients, summarizing similarities and differences in virus-induced cellular signaling relevant to the viral life cycles and liver disease progression.
Allosteric Inter-Domain Contacts in Bacterial Hsp70 Are Located in Regions That Avoid Insertion and Deletion Events
Authors: Gala Michal , Pristaš Peter , Žoldák Gabriel
Published: March 2022

Heat shock proteins 70 (Hsp70) are chaperones consisting of a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD), the latter of which binds protein clients. After ATP binds to the NBD, the SBD α/β subdomains’ shared interface opens, and the open SBD docks to the NBD. Such allosteric effects are stabilized by the newly formed NBD-SBD interdomain contacts. In this paper, we examined how such an opening and formation of subdomain interfaces is affected during the evolution of Hsp70. In particular, insertion and deletion events (indels) can be highly disruptive for the mechanical events since such changes introduce a collective shift in the pairing interactions at communicating interfaces. Based on a multiple sequence alignment analysis of data collected from Swiss-Prot/UniProt database, we find several indel-free regions (IFR) in Hsp70. The two largest IFRs are located in interdomain regions that participate in allosteric structural changes. We speculate that the reason why the indels have a lower likelihood of occurrence in these regions is that indel events in these regions cause dysfunction in the protein due to perturbations of the mechanical balance. Thus, the development of functional allosteric machines requires including in the rational design a concept of the balance between structural elements.
Identification and Functional Analysis of a Defensin CcDef2 from Coridius chinensis
Authors: Gong Tao , Du Juan , Li Shang-Wei , Huang Hai , Qi Xiao-Lang
Published: March 2022

Coridius chinensis belongs to Dinidoridae, Hemiptera. Previous studies have indicated that C. chinensis contains abundant polypeptides with antibacterial and anticancer activities. Antimicrobial peptides (AMPs), as endogenous peptides with immune function, play an indispensable role in the process of biological development and immunity. AMPs have become one of the most potential substitutes for antibiotics due to their small molecular weight and broad-spectrum antimicrobial activity. In this study, a defensin CcDef2 from C. chinensis was characterized based on bioinformatics and functional analyses. The mature peptide of CcDef2 is a typical cationic peptide composed of 43 amino acid residues with five cations, and contains three intramolecular disulfide bonds and a typical cysteine-stabilized αβ motif in defensins. Phylogenetic analysis showed that CcDef2 belongs to the insect defensin family. Analysis of gene expression patterns showed that CcDef2 was expressed throughout developmental stages of C. chinensis with high levels at the nymphal stage and in adult tissues tested with the highest level in the fat body. In addition, the CcDef2 expression was significantly upregulated in adults infected by bacteria. After expressed in Escherichia coli BL21(DE3) and renatured, the recombinant CcDef2 showed a significant antibacterial effect on three kinds of Gram-positive bacteria. These results indicate that CcDef2 is an excellent antibacterial peptide and a highly effective immune effector in the innate immunity of C. chinensis. This study provides a foundation for further understanding the function of CcDef2 and developing new antimicrobial drugs.
Homeostasis and Cancer Initiation: Organoids as Models to Study the Initiation of Gastric Cancer
Authors: Idowu Sulaimon , Bertrand Paul P. , Walduck Anna K.
Published: March 2022

Gastric cancer represents a significant disease burden worldwide. The factors that initiate cancer are not well understood. Chronic inflammation such as that triggered by H. pylori infection is the most significant cause of gastric cancer. In recent years, organoid cultures developed from human and animal adult stem cells have facilitated great advances in our understanding of gastric homeostasis. Organoid models are now being exploited to investigate the role of host genetics and bacterial factors on proliferation and DNA damage in gastric stem cells. The impact of a chronic inflammatory state on gastric stem cells and the stroma has been less well addressed. This review discusses what we have learned from the use of organoid models to investigate cancer initiation, and highlights questions on the contribution of the microbiota, chronic inflammatory milieu, and stromal cells that can now be addressed by more complex coculture models.
Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson’s Disease Mouse Model
Authors: Ruan Zhengzheng , Zhang Dongdong , Huang Ruixue , Sun Wei , Hou Liyan , Zhao Jie , Wang Qingshan
Published: March 2022

Chronic neuroinflammation has been considered to be involved in the progressive dopaminergic neurodegeneration in Parkinson’s disease (PD). However, the mechanisms remain unknown. Accumulating evidence indicated a key role of the blood–brain barrier (BBB) dysfunction in neurological disorders. This study is designed to elucidate whether chronic neuroinflammation damages dopaminergic neurons through BBB dysfunction by using a rotenone-induced mouse PD model. Results showed that rotenone dose-dependently induced nigral dopaminergic neurodegeneration, which was associated with increased Evans blue content and fibrinogen accumulation as well as reduced expressions of zonula occludens-1 (ZO-1), claudin-5 and occludin, three tight junction proteins for maintaining BBB permeability, in mice, indicating BBB disruption. Rotenone also induced nigral microglial activation. Depletion of microglia or inhibition of microglial activation by PLX3397 or minocycline, respectively, greatly attenuated BBB dysfunction in rotenone-lesioned mice. Mechanistic inquiry revealed that microglia-mediated activation of matrix metalloproteinases-2 and 9 (MMP-2/-9) contributed to rotenone-induced BBB disruption and dopaminergic neurodegeneration. Rotenone-induced activation of MMP-2/-9 was significantly attenuated by microglial depletion and inactivation. Furthermore, inhibition of MMP-2/-9 by a wide-range inhibitor, SB-3CT, abrogated elevation of BBB permeability and simultaneously increased tight junctions expression. Finally, we found that microglial depletion and inactivation as well as inhibition of MMP-2/-9 significantly ameliorated rotenone-elicited nigrostriatal dopaminergic neurodegeneration and motor dysfunction in mice. Altogether, our findings suggested that microglial MMP-2/-9 activation-mediated BBB dysfunction contributed to dopaminergic neurodegeneration in rotenone-induced mouse PD model, providing a novel view for the mechanisms of Parkinsonism.
Conformational Stabilization of Gp41-Mimetic Miniproteins Opens Up New Ways of Inhibiting HIV-1 Fusion
Authors: Cano-Muñoz Mario , Lucas Julie , Lin Li-Yun , Cesaro Samuele , Moog Christiane , Conejero-Lara Francisco
Published: March 2022

Inhibition of the HIV-1 fusion process constitutes a promising strategy to neutralize the virus at an early stage before it enters the cell. In this process, the envelope glycoprotein (Env) plays a central role by promoting membrane fusion. We previously identified a vulnerability at the flexible C-terminal end of the gp41 C-terminal heptad repeat (CHR) region to inhibition by a single-chain miniprotein (named covNHR-N) that mimics the first half of the gp41 N-terminal heptad repeat (NHR). The miniprotein exhibited low stability, moderate binding to its complementary CHR region, both as an isolated peptide and in native trimeric Envs, and low inhibitory activity against a panel of pseudoviruses. The addition of a disulfide bond stabilizing the miniprotein increased its inhibitory activity, without altering the binding affinity. Here, to further study the effect of conformational stability on binding and inhibitory potency, we additionally stabilized these miniproteins by engineering a second disulfide bond stapling their N-terminal end, The new disulfide-bond strongly stabilizes the protein, increases binding affinity for the CHR target and strongly improves inhibitory activity against several HIV-1 strains. Moreover, high inhibitory activity could be achieved without targeting the preserved hydrophobic pocket motif of gp41. These results may have implications in the discovery of new strategies to inhibit HIV targeting the gp41 CHR region.
Unsupervised Learning in Drug Design from Self-Organization to Deep Chemistry
Authors: Polanski Jaroslaw
Published: March 2022

The availability of computers has brought novel prospects in drug design. Neural networks (NN) were an early tool that cheminformatics tested for converting data into drugs. However, the initial interest faded for almost two decades. The recent success of Deep Learning (DL) has inspired a renaissance of neural networks for their potential application in deep chemistry. DL targets direct data analysis without any human intervention. Although back-propagation NN is the main algorithm in the DL that is currently being used, unsupervised learning can be even more efficient. We review self-organizing maps (SOM) in mapping molecular representations from the 1990s to the current deep chemistry. We discovered the enormous efficiency of SOM not only for features that could be expected by humans, but also for those that are not trivial to human chemists. We reviewed the DL projects in the current literature, especially unsupervised architectures. DL appears to be efficient in pattern recognition (Deep Face) or chess (Deep Blue). However, an efficient deep chemistry is still a matter for the future. This is because the availability of measured property data in chemistry is still limited.
Comparative Analysis of Mitochondrial Genomes among Twelve Sibling Species of the Genus Atkinsoniella Distant, 1908 (Hemiptera: Cicadellidae: Cicadellinae) and Phylogenetic Analysis
Authors: Jiang Yan , Li Hao-Xi , Yu Xiao-Fei , Yang Mao-Fa
Published: March 2022

The herbivorous leafhopper genus Atkinsoniella Distant, 1908 (Hemiptera: Cicadellidae: Cicadellinae), a large genus of subfamily Cicadellinae, consists of 98 valid species worldwide and 88 species recorded in China. Some species of the genus are very similar in morphological characteristics, so they are difficult to identify accurately. In this study, 12 mitochondrial genomes of Atkinsoniella species with similar morphological characteristics were first obtained through high-throughput sequencing, which featured a typical circular molecule of 15,034–15,988 bp in length. The arrangement and orientation of 37 genes were identical to those of typical Cicadellidae mitogenomes. The phylogenetic relationship within the subfamily Cicadellinae was reconstructed using maximum-likelihood (ML) and Bayesian inference (BI) methods based on three concatenated datasets. The topological structures of the six obtained phylogenetic trees were highly consistent. The results suggested that Atkinsoniella was recovered as a monophyletic group and emerged as a sister group with the monophyletic clade of Bothrogonia, Paracrocampsa (part), and Draeculacephala (part). The branches of the 12 newly sequenced species were clearly separated, with most nodes receiving strong support in all analyses. In addition, the key to the 12 Atkinsoniella species was provided to identify species according to morphological characteristics. This study further promotes research on the classification, genetics, evolution, and phylogeny of the genus Atkinsoniella and subfamily Cicadellinae.
Scheduling UWB Ranging and Backbone Communications in a Pure Wireless Indoor Positioning System
Authors: Charlier Maximilien , Koutsiamanis Remous-Aris , Quoitin Bruno
Published: March 2022

In this paper, we present and evaluate an ultra-wideband (UWB) indoor processing architecture that allows the performing of simultaneous localizations of mobile tags. This architecture relies on a network of low-power fixed anchors that provide forward-ranging measurements to a localization engine responsible for performing trilateration. The communications within this network are orchestrated by UWB-TSCH, an adaptation to the ultra-wideband (UWB) wireless technology of the time-slotted channel-hopping (TSCH) mode of IEEE 802.15.4. As a result of global synchronization, the architecture allows deterministic channel access and low power consumption. Moreover, it makes it possible to communicate concurrently over multiple frequency channels or using orthogonal preamble codes. To schedule communications in such a network, we designed a dedicated centralized scheduler inspired from the traffic aware scheduling algorithm (TASA). By organizing the anchors in multiple cells, the scheduler is able to perform simultaneous localizations and transmissions as long as the corresponding anchors are sufficiently far away to not interfere with each other. In our indoor positioning system (IPS), this is combined with dynamic registration of mobile tags to anchors, easing mobility, as no rescheduling is required. This approach makes our ultra-wideband (UWB) indoor positioning system (IPS) more scalable and reduces deployment costs since it does not require separate networks to perform ranging measurements and to forward them to the localization engine. We further improved our scheduling algorithm with support for multiple sinks and in-network data aggregation. We show, through simulations over large networks containing hundreds of cells, that high positioning rates can be achieved. Notably, we were able to fully schedule a 400-cell/400-tag network in less than 11 s in the worst case, and to create compact schedules which were up to 11 times shorter than otherwise with the use of aggregation, while also bounding queue sizes on anchors to support realistic use situations.
Advances in the Treatment Strategies in Hypertension: Present and Future
Authors: Verdecchia Paolo , Cavallini Claudio , Angeli Fabio
Published: March 2022

Hypertension is the most frequent chronic and non-communicable disease all over the world, with about 1.5 billion affected individuals worldwide. Its impact is currently growing, particularly in low-income countries. Even in high-income countries, hypertension remains largely underdiagnosed and undertreated, with consequent low rates of blood pressure (BP) control. Notwithstanding the large number of clinical observational studies and randomized trials over the past four decades, it is sad to note that in the last few years there has been an impressive paucity of innovative studies. Research focused on BP mechanisms and novel antihypertensive drugs is slowing dramatically. The present review discusses some advances in the management of hypertensive patients, and could play a clinical role in the years to come. First, digital/health technology is expected to be increasingly used, although some crucial points remain (development of non-intrusive and clinically validated devices for ambulatory BP measurement, robust storing systems enabling rapid analysis of accrued data, physician-patient interactions, etc.). Second, several areas should be better outlined with regard to BP diagnosis and treatment targets. Third, from a therapeutic standpoint, existing antihypertensive drugs, which are generally effective and well tolerated, should be better used by exploiting available and novel free and fixed combinations. In particular, spironolactone and other mineral-corticoid receptor antagonists should be used more frequently to improve BP control. In particular, some drugs initially developed for conditions different from hypertension including heart failure and diabetes have demonstrated to lower BP significantly and should therefore be considered. Finally, renal artery denervation is another procedure that has proven effective in the management of hypertension.
Using the NYHA Classification as Forecasting Tool for Hospital Readmission and Mortality in Heart Failure Patients with COVID-19
Authors: Citu Ioana Mihaela , Citu Cosmin , Gorun Florin , Neamtu Radu , Motoc Andrei , Burlea Bogdan , Rosca Ovidiu , Bratosin Felix , Hosin Samer , Manolescu Diana , Patrascu Raul , Gorun Oana Maria
Published: March 2022

During the COVID-19 pandemic, it was observed that patients with heart disease are more likely to be hospitalized and develop severe COVID-19. Cardiac disease takes the top position among patient comorbidities, heart failure (HF) prevalence reaching almost 5% in the general population older than 35 years in Romania. This retrospective study aimed to determine the potential use of the NYHA classification for HF in hospitalized patients with COVID-19 as prognostic tool for in-hospital mortality, length of hospitalization, and probability of rehospitalization for HF decompensation. We observed that patients with advanced HF had a history of significantly more comorbid conditions that are associated with worse disease outcomes than the rest of patients classified as NYHA I and II. However, regardless of existing diseases, NYHA III, and, especially, NYHA IV, patients were at greatest risk for mortality following SARS-CoV-2 infection. They required significantly longer durations of hospitalization, ICU admission for mechanical ventilation, and developed multiple severe complications. NYHA IV patients required a median duration of 20 days of hospitalization, and their in-hospital mortality was as high as 47.8%. Cardiac biomarkers were significantly altered in patients with SARS-CoV-2 and advanced HF. Although the study sample was small, all patients with NYHA IV who recovered from COVID-19 required a rehospitalization in the following month, and 65.2% of the patients at initial presentation died during the next six months. The most significant risk factor for mortality was the development of severe in-hospital complications (OR = 4.38), while ICU admission was the strongest predictor for rehospitalization (OR = 5.19). Our result highlights that HF patients continue to be vulnerable post SARS-CoV-2 infection. Physicians and policymakers should consider this population’s high likelihood of hospital readmissions when making discharge, hospital capacity planning, and post-discharge patient monitoring choices.
The Application of an Allogenic Bone Screw for Stabilization of a Modified Chevron Osteotomy: A Prospective Analysis
Authors: Huber Thorsten , Hofstätter Stefan G. , Fiala Rainer , Hartenbach Florian , Breuer Robert , Rath Björn
Published: March 2022

Background: Distal first metatarsal osteotomies are commonly performed operative procedures for hallux valgus deformity, and usually involve fixation with a metal screw. However, various bioabsorbable osteosynthesis materials have been in use for a number of years. One recent innovation is the Shark Screw®, a human cortical bone allograft. This study aimed to evaluate the efficacy and safety of this allogeneic screw in the stabilization of Reversed L-Shaped osteotomy, a modified Chevron osteotomy. Methods: In a prospective study, 15 patients underwent a Reversed L-Shaped osteotomy stabilized with the allogenic bone screw Radiological data on osteointegration of the screw and correction of the intermetatarsal angle were recorded. Furthermore, each follow-up examination included the collection of clinical data, the American Orthopedic Foot and Ankle Society (AOFAS) score, evaluation of pain level, and patient’s overall satisfaction. Results: Full osseous fusion of the osteotomy was seen in all patients. The bone screws were radiographically integrated after approximately 6.5 (±2.6) months. Neither nonunion nor failure occurred in any of our cases. Furthermore, we did not find any potential graft reaction. The AOFAS score improved significantly from 51.6 (±15.2) points to 90.9 (±10.3) (p < 0.001). The preoperative hallux valgus angle and intermetatarsal angle decreased significantly from 24.8 (±4.9) degrees to 7.2 (±4.4) degrees (p < 0.001) and 12.6 (±3.2) degrees to 4.8 (±1.3) degrees (p < 0.001), respectively. Conclusions: With this study, we demonstrated the efficiency of the allogenic bone screw (Shark Screw®) in regard to clinical and radiological short-term outcomes.
Pharmacological Treatment in Presbyopia
Authors: Grzybowski Andrzej , Ruamviboonsuk Varis
Published: March 2022

Pharmacological treatment of presbyopia may be an alternative for those who want a spectacle-free scenario and an easy-to-use method with lower risk of irreversible ocular adverse events. There are two main agents, miotics and lens softeners, investigated as agents for the pharmacological treatment. Miotic agents treat presbyopia by creating a pinhole effect which may increase the depth of focus at all working distances. The miotic agents have been studied for application to only one eye for monovision or both eyes. Their effect is temporary with common adverse events, such as headache and dim vision at nighttime, with no known long-term safety and efficacy. There have been studies on the miotic agents in combination with other agents for additive treatment effects or lessening adverse events, however, these combination effects are not clear. Lens softeners increase the elasticity of the lens, which is targeted at one of the etiologic mechanisms of presbyopia. There is only one lens softener being investigated in only a few trials. The results were inconclusive. The recent approval of 1.25% pilocarpine for treatment of presbyopia by the US FDA may be an important milestone for investigation of real-world data of pharmacological treatment of presbyopia.