bluuebunny/crossref_metadata_2025 huggingface dataset:
Islamic Guidance Model Case Study of New Students who Repeat Class at Madrasah Qudsiyyah Kudus
Authors: Ihsan Ihsan
Published: January 2021

This study aims to describe how the Islamic guidance model is implemented at Madrasah Qudsiyyah. It is as part of the process of transforming the religious behavior of new students who repeat the class and how their religious behavior in the class. This study used a phenomenological approach with qualitative research method. Data were obtained through observation, interviews and documentation, then analyzed and concluded. The results of this study indicate that the students who repeat at Madrasah Qudsiyyah are new students who based on the entry selection test, their abilities are below the average so they must repeat in fifth or sixth grade of MI. Even though they have graduated from SD or MI in previous schools, as well as when they enter the Aliyah level, most of them will repeat in ninth grade of MTs Qudsiyyah. habituation. Using this way, the teachers succeeded in changing the santri attitude to be more enthusiastic, optimistic, istiqamah and tawadlu'.
Pre-Marriage Guidance as an Effort to Form Harmonious Families in the Office of Religious Affairs (KUA) Perspective of Islamic Satisfaction
Authors: Saliyo Saliyo , Sanusi Sanusi , Putri Risqi Nidiya
Published: January 2021

This study aims to determine Pre-Marriage Guidance as an Effort to Form Harmonious Families in the Office of Religious Affairs (KUA) Perspective of Islamic Satisfaction and some of its problems. This research was conducted at the Office of Religious Affairs (KUA) of Bae Kudus District. This article is the result of field research with a qualitative approach. Data collection uses interview, observation and documentation and triangulation methods. The number of informants is 12 people using non-possible sampling and the determination of informants by purposive sampling. The results showed that: a) The role of religious counselors as guides in providing pre-marital guidance can form harmonious families with the satisfaction of Islamic marriage. With the couple's notes running the material delivered in pre-marital guidance; b) Pre-marital guidance in KUA of Bae District is carried out after an examination of administrative data of the bride and groom is carried out within 30-60 minutes. Material delivered about the ins and outs of married life to be fostered in the future. Among them are the rights and obligations as husband and wife and so forth. The methods used in pre-marital guidance are lectures, questions and answers and discussions in the form of seminars; c) Problems in pre-marital guidance activities include lack of time, lack of concern for the catin (bride-to-be), the distance where Catin lives and funding from the government. Things that support are a comfortable environment, knowledge of qualified religious instructors, pre-supporting facilities and good KUA citizen participation.
The Effect of Lifestyle and Risk Factor Modification on Occlusive Peripheral Arterial Disease Outcomes: Standard Healthcare vs Structured Programme: for a Randomised Controlled Trial Protocol
Authors: Elfghi Marah , Jordan Fionnuala , Dunne Denise , Gibson Irene , Jones Jennifer , Flaherty Gerard , Sultan Sherif , Tawfick Wael
Published: January 2021

Background Peripheral arterial disease (PAD) affects more than 200 million of the global population. PAD represents a marker for premature cardiovascular events. Patients with PAD, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as patients with a history of coronary or cerebrovascular disease. Despite the high prevalence of PAD and the strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive appropriate treatment for their atherosclerotic risk factors than those who are being treated for coronary artery disease. Atherosclerotic risk factor identification and modification play an important role in reducing the number of adverse outcomes among patients with atherosclerosis. Risk reduction therapy decreases the risk of cardiovascular mortality and morbidity in patients with PAD. In this study we aim to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors Methods This is a randomised, parallel group, active-control trial to compare the effectiveness of the risk factor modification intervention programme to standard healthcare in a tertiary vascular care centre, in the reduction of modified risk factors in PAD patients. The primary outcome of this study is to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors at 3 and 12 months. The secondary outcomes are to compare the impact of the programme on clinical outcomes in PAD patients at 12 months. Secondary outcomes include amputation-free survival, clinical improvement, haemodynamic improvement, need for revascularisation procedures, outcomes of revascularisation procedures, changes in quality of life and the incidence of adverse events. Discussion This study will provide clear evidence on the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors, through a high quality, well-powered clinical trial. Trial registration This trial was registered (11/07/2017) on the European Clinical Trials Database (EudraCT number 2017-002964-41) and ClinicalTrials.gov (NCT03935776) which was registered on 02 May 2019.
How does the self-reported health of undergraduate nursing students change during their degree programme? Survey results from a Scottish University
Authors: Evans Josie , Andreis Federico , Cameron Dawn M , Eades Claire E
Published: January 2021

Background: The lifestyle behaviours, and the physical and mental health of nurses, are poorer than those of other allied health professionals, and of the general population. However, these were no less favourable among first year undergraduate nursing students at a Scottish Higher Education Institution (HEI) than among similar people of the same age. We compared health and health behaviours among the same cohort of undergraduate nursing students over the course of their degree. Methods: An anonymous self-complete repeat cross-sectional survey was administered during a timetabled teaching session at three time-points to undergraduate nursing students at the start of Years 1, 2 and 3 of their programme. They had received written information about the study previously. Results: Self-reported health did not change significantly over time, but there was a clear decline over the three years in the proportions of students rating their mental health as excellent/very good/good and a concomitant increase in those rating their mental health as fair/poor. Correspondingly, the mean WEMWBS wellbeing score declined over the three years, with the proportion of students with a score of <46 (indicating either high risk of major depression, or in high risk of psychological distress and increased risk of depression) increasing from one quarter to one half. This effect was captured and described using a Bayesian regression analysis. The most noticeable change in health behaviours was a decline in physical activity levels over the study period. The proportion of students managing 150 minutes of weekly physical activity decreased from three quarters to two thirds. This was reflected in higher self-reported sedentary time, although there were no observable trends over time in mean BMI, or proportions of students categorised as overweight or obese. Conclusions: This paper suggests that there may be a decline in mental health and in participation in physical activity among nursing students over the course of their degree. We recommend the incorporation of an intervention into the undergraduate nursing curriculum that promotes and encourages regular physical activity, offering students the opportunity to learn about health promotion and lifestyle change in practice, to improve their own physical health, and to address mental wellbeing.
Subjective sleep quality and association with depression syndrome, chronic diseases and health-related physical fitness in the middle-aged and elderly
Authors: Hsu Min-Fang , Lee Kang-Yun , Lin Tsung-Ching , Liu Wen-Te , Ho Shu-Chuan
Published: January 2021

Background: As a complex phenomenon, sleep quality is difficult to objectively define and measure, and multiple factors related to sleep quality, such as age, lifestyle, physical activity, and physical fitness, feature prominently in older adult populations. The aim of the present study was to evaluate subjective sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and to associate sleep quality with health-related physical fitness factors, depressive symptoms, and the number of chronic diseases in the middle-aged and elderly.Methods: We enrolled a total of 283 middle-aged and elderly participants from a rehabilitation clinic or health examination department. The PSQI was used to evaluate sleep quality. The health-related fitness assessment included anthropometric and physical fitness parameters. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D) short form. Data were analyzed with SPSS 18.0, and descriptive statistics and logistic regression analysis were used for the analyses.Results: Overall, 27.9% of participants in this study demonstrated bad sleepers (with a PSQI score of >5), 10.2% of study participants frequently used sleep medication to help them fall asleep, and 6.0% reported having significant depressive symptoms (with a CES-D score of ≥10). There are two major findings: (1) depression symptoms, the number of chronic diseases, self-rated health, and arthritis were significantly associated with a poor sleep quality, and (2) the 2-min step test was associated with longer sleep latency. These results confirmed that the 2-min step was associated with a longer sleep latency among the health-related physical fitness items.Conclusions: Our study found that depressive syndrome, chronic disease numbers, a poor self-rated health status, and arthritis were the main risk factors that influenced subjective sleep quality.
Exceptional parallelisms characterize the evolutionary transition to live birth in phrynosomatid lizards
Authors: Domínguez-Guerrero Saúl , Cruz Fausto Méndez-de la , Manríquez-Morán Norma , Olson Mark , Galina-Tessaro Patricia , Arenas-Moreno Diego , Moral Adán Bautista-del , Benítez-Villaseñor Adriana , Gadsden Héctor , Lara-Reséndiz Rafael , Maciel-Mata Carlos , Muñoz-Nolasco Francisco , Santos-Bibiano Rufino , Valdez-Villavicencio Jorge , Woolrich-Piña Guillermo , Muñoz Martha
Published: January 2021

Viviparity is an evolutionary innovation that enhances maternal protection of developing embryos relative to egg-laying ancestors. The behavioral, physiological, morphological, and life history pathways underpinning this innovation, however, remain unclear. We capitalized on the repeated origin of viviparity in phrynosomatid lizards to tease apart the phenotypic patterns associated with evolutionary transitions to live birth. We detected tandem reductions in mass-specific metabolic rate and mass-specific production in viviparous lineages, in turn reflecting decreases in thermal physiology and fecundity, respectively. These pathways reduce the energetic burden of viviparity without concomitant reductions in offspring body size. Although viviparous lizards are more prevalent in cold environments, transitions in thermal habitat only weakly predict parity mode evolution. Likewise, only cold tolerance adapts rapidly to thermal environment. Heat tolerance and preferred body temperatures track the thermal environment, but with a lag at million-year timescales. This lag likely reflects behavioral buffering: viviparous lizards thermoregulate to low body temperatures, regardless of ambient conditions. Rather than representing an adaptation to cold climates, the lower thermal and metabolic physiology of viviparous species are likely an energetic adjustment for reproduction that facilitated their prolific colonization of cooler environments.
Beneficial land-use change in Europe: deployment scenarios for multifunctional riparian buffers and windbreaks
Authors: Englund Oskar , Börjesson Pål , Mola-Yudego Blas , Berndes Göran , Dimitriou Ioannis , Cederberg Christel , Scarlat Nicolae
Published: January 2021

The land sector needs to increase biomass production to meet multiple demands while reducing negative land use impacts and transitioning from being a source to being a sink of carbon. The new Common Agricultural Policy of the EU (CAP) steers towards a more needs-based, targeted approach to addressing multiple environmental and climatic objectives, in coherence with other EU policies. In relation to this, new schemes are developed to offer farmers direct payments to adapt practices beneficial for climate, water, soil, air and biodiversity. Multifunctional biomass production systems have potential to reduce environmental impacts from agriculture while maintaining or increasing biomass production for the bioeconomy across Europe. Here, we present the first attempt to model the deployment of two such systems, riparian buffers and windbreaks, across >81.000 landscapes in Europe (EU27 + UK), aiming to quantify the resulting ecosystem services and environmental benefits, considering three deployment scenarios with different incentives for implementation. We found that these multifunctional biomass production systems can reduce N emissions to water and soil loss by wind erosion, respectively, down to a “low” impact level all over Europe, while simultaneously providing substantial environmental co-benefits, using less than 1% of the area under annual crops in the EU. The GHG emissions savings of utilizing the biomass produced in these systems for replacing fossil alternatives, combined with the increases in soil organic carbon, correspond to 1-1,4% of total GHG emissions in EU28. The introduction of “eco-schemes” in the new CAP may resolve some of the main barriers to implementation of large-scale multifunctional biomass production systems. Increasing the knowledge of these opportunities among all EU member states, before designing and introducing country-specific Eco-scheme options in the new CAP, is critical.
Fluorescence umpolung enables light-up sensing of N-acetyltransferases and nerve agents
Authors: Yan Chenxu , Guo Zhiqian , Chi Weijie , Fu Wei , Liu Xiaogang , Tian He , Zhu Wei-Hong
Published: January 2021

Intramolecular charge transfer (ICT) is a fundamental mechanism that enables the development of numerous fluorophores and probes for bioimaging and sensing. However, the electron-withdrawing targets (EWTs)-induced fluorescence quenching is a long-standing and unsolved issue in ICT fluorophores, and significantly limits the widespread applicability. Here we report a simple and generalizable structural-modification for completely overturning the intramolecular rotation driving energy, and thus fully reversing the ICT fluorophores’ quenching mode into light-up mode. Specifically, the insertion of an indazole unit into ICT scaffold can fully amplify the intramolecular rotation in donor-indazole-π-acceptor fluorophores (fluorescence OFF), whereas efficiently suppressing the rotation in their EWT-substituted system (fluorescence ON). The novel molecular strategy is generalizable, yielding a palette of chromophores with fluorescence umpolung that spans visible and near-infrared range. This strategy expands the bio-analytical toolboxes and has for the first time allowed exploiting ICT fluorophores for unprecedented light-up sensing of EWTs including N-acetyltransferases and nerve agents.
Synbiotic Combinations of Lactobacillus Gasseri 505 and Cudrania Tricuspidata Leaf Extracts Ameliorate Reproductive Dysfunction in Mice Under Chronic Stress
Authors: Oh Nam Su , Kim Sae Hun , Joung Jae Yeon , Lim Whasun , Ham Jiyeon , Seo Yeon Jeong
Published: January 2021

The objective of this study was to investigate the effects of Lactobacillus gasseri 505 (505) and the synbiotic combination of 505 and Cudrania tricuspidata leaf extracts (CT) on the hypothalamic-pituitary-gonadal axis in mice during chronic stress. In our previous study, a synbiotic combination (Syn) of a fermented CT-supplemented milk with 505 exhibited good anti-inflammatory and hepatoprotective activities in mice. Therefore, we hypothesized that a Syn may exert some preventive effects in the male reproductive system when suffering from unpredictable chronic mild stress (UCMS). UCMS significantly decreased the serum levels of corticosterone, however, treatment with 505 and its Syn suppressed UCMS-induced decreases. Histopathological analysis of the testes showed that these organs experienced some damage during UCMS, but this was repaired following treatment with 505 or Syn. Similarly, the transcription levels of gonadotropin-releasing hormone (GnRH), GnRH receptor, and gonadotropins, moreover, testicular development (i.e., Adam5, Adam29, and Spam1) - and steroidogenesis (i.e., Lhr, Egfr, and StAR) -related genes were significantly downregulated by UCMS. These UCMS-induced changes were inhibited following the administration of 505 or Syn, which was confirmed by the results of in situ hybridization analysis. These results suggest that the administration of a Syn could attenuate the testicular dysfunctions induced by UCMS.
Embedding Supervised Exercise Training for Men on Androgen Deprivation Therapy Into Standard Prostate Cancer Care: A Feasibility and Acceptability Study
Authors: Reale Sophie , Turner Rebecca , Sutton Eileen , Steed Liz , Taylor Stephanie , Morrissey Dylan , Doherty Patrick , Greenfield Diana , Collinson Michelle , Hewison Jenny , Brown Janet , Ibeggazene Said , Mason Malcolm , Rosario Derek , Bourke Liam
Published: January 2021

Lifestyle interventions involving exercise training offset the adverse effects of androgen deprivation therapy in men with prostate cancer (PCa). Yet provision of integrated exercise pathways in cancer care is sparse. This study assessed the feasibility and acceptability of an embedded supervised exercise training intervention into standard PCa care in a single-arm, multicentre prospective cohort study. Feasibility included recruitment, retention, adherence, fidelity and safety. Acceptability of behaviourally informed healthcare and exercise professional training was assessed qualitatively. Despite the imposition of lockdown for the COVID-19 pandemic, referral rates into and adherence to, the intervention was high. Of the 45 men eligible for participation, 79% received the intervention. Patients completed a mean of 27 minutes of aerobic exercise per session (SD=3.48), at 77% heart rate maximum (92% of target dose), and 3 sets of 10 reps of 3 resistance exercises twice weekly for 12 weeks, without serious adverse event. The intervention was delivered by healthcare and exercise professionals with moderate to high fidelity and the intervention was deemed highly acceptable to patients. The impact of societal changes due to the pandemic on the delivery of this face-to-face intervention remain uncertain but positive impacts of embedding exercise provision into PCa care warrant long-term investigation.
Reconstructing Network Structures from Partial Measurements
Authors: Tyloo Melvyn , Delabays Robin , Jacquod Philippe
Published: January 2021

The dynamics of systems of interacting agents is determined by the structure of their coupling
network. The knowledge of the latter is therefore highly desirable, for instance to develop efficient
control schemes, to accurately predict the dynamics or to better understand inter-agent processes.
In many important and interesting situations, the network structure is not known, however, and
previous investigations have shown how it may be inferred from complete measurement time series,
on each and every agent. These methods implicitly presuppose that, even though the network is not
known, all its nodes are. A major shortcoming of theirs is that they cannot provide any reliable
information, not even on partial network structures, as soon as some agents are unobservable.
Here, we construct a novel method that determines network structures even when not all agents
are measurable. We establish analytically and illustrate numerically that velocity signal correlators
encode not only direct couplings, but also geodesic distances in the coupling network, within the
subset of measurable agents. When dynamical data are accessible for all agents, our method is
furthermore algorithmically more efficient than the traditional ones, because it does not rely on
matrix inversion.
Immunological Off-Target Effects of microRNA Control Sequences.
Authors: Al-Modawi Rua , Brinchmann Jan , Karlsen Tommy
Published: January 2021

Immunological off-target effects of RNA and RNAi therapy are a considerable challenge in research and the future of RNA-therapy. Here we investigated some of the hurdles we previously encountered when transfecting mircroRNA (miRNA) control sequences into chondrocytes in an inflammatory model simulating osteoarthritis (OA). We investigated different negative control sequences of different technologies; Pre-miR miRNA Precursor and mirVana from Thermo Fisher Scientific. We used RT-qPCR, western blot analysis and mass spectrometry to asses for the effects of the transfected control sequences.The data did not show a global immunological off-target effect, however a specific off-target effect on IL6 and IL8 was observed. IL6 and IL8 were both upregulated by the negative control from the Pre-miR miRNA Precursor technology (Pre-neg #1), and downregulated by the negative control from the mirVana technology (mirVana-neg). Moreover, the results suggested that the effect on IL6 and IL8 was dependent on both sequence and type of chemical modifications in addition to donor variation. We conclude that negative controls should be selected wisely, and suggest that scientists need to test several controls to ensure correct interpretation of data before drawing any conclusions.
Whole exome sequencing and gene expression analysis of canine osteosarcomas identify mutant TP53 and enriched immune pathways associated with longer survival
Authors: Das Sunetra , Idate Rupa , Regan Daniel , Fowles Jared , Lana Susan , Thamm Douglas , Gustafson Daniel , Duval Dawn
Published: January 2021

Osteosarcoma affects about 2.8% of dogs with cancer, with a one-year survival rate of approximately 45%. The purpose of this study was to characterize the mutation and expression profiles of canine osteosarcoma associated with outcome in samples from dogs treated by amputation and chemotherapy.
The number of somatic variants identified across 26 samples ranged from 145 to 2,697 with top recurrent mutations observed in TP53 (82% of the samples) and SETD2 (22%). Additionally, 47 cancer genes were identified with copy number variations in at least 58% of the samples. We observed transcriptional down-regulation of myogenesis genes and up-regulation of extracellular matrix genes in tumors compared to normal bone. Patients with longer disease-free intervals (DFI) showed increased transcript levels of anti-tumor immune response genes. Wild-type/NULL TP53 mutation status and high pre-treatment blood monocyte counts were associated with a shorter DFI. Immune cell infiltration was quantified via immunohistochemistry and gene expression profiling. CD3+ and MAC387+ myeloid cell quantifications were not significantly associated with outcome. Expression of immune related genes PDL-1, CD160 and ICOS were correlated with T-cell abundance.
Overall, the association of gene expression and mutation profiles to outcome provides insights into pathogenesis and therapeutic interventions in osteosarcoma patients.
Realising and Compressing Quantum Circuits With Quantum Reservoir Computing
Authors: Ghosh Sanjib , Krisnanda Tanjung , Paterek Tomasz , Liew Timothy
Published: January 2021

Quantum computers require precise control over parameters and careful engineering of the underlying physical system. In contrast, neural networks have evolved to tolerate imprecision and inhomogeneity. Here, using a reservoir computing architecture we show how a random network of quantum nodes can be used as a robust hardware for quantum computing. It induces quantum operations by optimising only a single layer of quantum nodes, a key advantage over the traditional neural networks where many layers of neurons have to be optimised. We demonstrate how a single network can induce different quantum gates, including a universal gate set. Moreover, we show that sequences of multiple quantum gates in quantum circuits can be compressed with a single operation, greatly reducing the operation time and complexity. As the key resource is a random network of nodes, with no specific topology or structure, this architecture is a hardware friendly alternative paradigm for quantum computation.
Global Health Effects of Future Atmospheric Mercury Emissions
Authors: Zhang Yanxu , Song Zhengcheng , Huang Shaojian , Zhang Peng , Peng Yiming , Wu Peipei , Gu Jing , Dutkiewicz Stephanie , Zhang Huanxin , Wu Shiliang , Wang Feiyue , Chen Long , Wang Shuxiao , Li Ping
Published: January 2021

Mercury (Hg) is a potent neurotoxin that poses health risks to the global population. Anthropogenic Hg emissions to the atmosphere are projected to decrease in the future due to enhanced policy efforts such as the Minamata Convention, a legally-binding international treaty entered into force in 2017. To project the health benefits of emission reduction requires considering both primary sources and recycling of previously deposited Hg from the land and ocean. Here we report the development of a comprehensive climate-atmosphere-land-ocean-ecosystem and exposure-risk model framework for Hg and its application to project the health effects of future atmospheric emissions. We find the projected Hg health risk changes nonlinearly with emission changes, and the most optimistic scenario (maximum feasible reduction, MFR) leads to Hg levels in the freshwater and marine biota half of the present-day levels. Our results show that the accumulated health effects associated with Hg exposure during 2010–2050 are $19 (range: 10–27) trillion (2020 USD) realized to 2050 (3% discount rate) for the current policy scenario. The MFR scenario is projected to have a health benefit of $2.4 trillion, while a business-as-usual scenario results in an additional $4.9 trillion health loss. Our results suggest a substantial increase in global human health cost if emission reduction actions are delayed. This comprehensive modeling approach provides a much-needed tool to help parties to evaluate the effectiveness of Hg emission controls as required by the Minamata Convention.
Regulation of Abnormal Expression of hsa_circRNA_0127523 on Proliferation, Migration and Invasion and miR-515-5p Expression in Oral Squamous Cell Carcinoma.
Authors: Wei Jianing , Wang Zekun , Gao Jiping , Liang Yuxiang , Xu Guoqiang , Wang Xiaotang , Xiao Lanfei , Yan Xiaoru , Song Guohua
Published: January 2021

Circular RNA (circRNA) play an important role in many biological processes of occurrence and development of cancers. In this research, we established an animal model by DMBA-induced buccal sac tissue and discovered the differential expression of circRNAs by the second-generation sequencing. Models were identified by HE staining and ultrastructural observation. We found total of 3485 circRNAs were differentially expressed which the top 8 different expression circRNAs in sequencing results were confirmed by qRT-PCR. GO and KEGG analyses showed that differently expressed circRNAs function and pathway. Moreover, the axis relationship of circRNA-miRNA was predicted by miRanda. Silencing hsa_circ_0127523 significantly suppressed the proliferation, migration and invasion abilities of oral squamous cell carcinoma (OSCC) cells by RNAi, CCK-8, transwell migration and invasion assays. Furthermore, bioinformatics databases suggested that hsa_circ_0127523 might function by sponging miR-515-5p to regulate the expression of TRIP13. It was subsequently identified that hsa_circ_0127523 may inhibit miR-515-5p expression and increase TRIP13 expression in the OSCC cells. In summary, the results of the present study revealed that OSCC tissues have abundant circRNAs and we firstly explore the role of the hsa_circ_0127523 in the behavior regulation of OSCC cells. Its demonstrating that hsa_circ_0127523 may be a potential biomarker and therapeutic target of OSCC.
SARS-CoV-2 protein encoded by ORF8 contains a histone mimic that disrupts chromatin regulation
Authors: Kee John , Thudium Samuel , Glastad Karl , Palozola Katherine , Zhang Zhen , Li Yize , Cesare Joseph , Truitt Rachel , Cardenas Fabian , Kotton Darrell , Alysandratos Konstantinos-Dionysios , Yang Wenli , Morrisey Edward , Garcia Benjamin , Weiss Susan , Berger Shelley , Korb Erica
Published: January 2021

SARS-CoV-2 emerged in China at the end of 2019 and caused the global pandemic of COVID-19, a disease with high morbidity and mortality. While our understanding of this novel virus is rapidly increasing, gaps remain in our understanding of how SARS-CoV-2 can effectively suppress host cell antiviral responses. Recent work on other viruses has demonstrated a novel mechanism through which viral proteins can mimic critical regions of human histone proteins. Histone proteins are responsible for governing genome accessibility and their precise regulation is critical for a cell’s ability to control transcription and respond to viral threats. Here, we show that the protein encoded by ORF8 (Orf8) in SARS-CoV-2 functions as a histone mimic of two critical histone 3 sites containing an ARKS motif. Orf8 expression in cells disrupts multiple critical histone post-translational modifications (PTMs) while Orf8 lacking this histone mimic motif does not. Orf8 binds to numerous histone-associated proteins and to DNA, and is itself acetylated within the histone mimic site. Importantly, SARS-CoV-2 infection of multiple susceptible cell types causes the same global changes of histone post-translational modifications that are disrupted by Orf8 expression; these include induced pluripotent stem cell-derived alveolar type 2 cells (iAT2) and cardiomyocytes (iCM) and postmortem patient lung tissue. These findings demonstrate a novel function for the poorly understood SARS-CoV-2 ORF8 encoded protein and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Notably, this work provides a potential mechanism for emerging findings from human patients indicating that ORF8 deletion results in less severe illness and describes a potentially druggable pathway that may contribute to the virulence of SARS-CoV-2.
Geothermal as resource for megacities
Authors: Vargas Carlos , Caracciolo Luca , Ball Philip
Published: January 2021

33 Megacities are distributed around the world, a number that will increase to 43 by 2030. Megacities are critical for the world’s economy, however, their management is particularly challenging in terms of transportation, water, waste, sanitation, security, electricity, and environmental impact. The increase of energy demand, in parallel to population growth and climate change, requires investment in sustainable energies. Geothermal energy – differently from solar, wind and hydroelectric is independent from weather conditions. A number of megacities around the world are located in areas with anomalous geothermal gradients, proximal to the margins of tectonic plates. This colocation makes geothermal an attractive resilient, baseload, low-carbon, energy source helping Megacities reduce their environmental impact. In this paper, we discuss the advantages of using geothermal energy, leading the study for the city of Bogotá, and applying the same workflow for Los Angeles and Jakarta. We aim to provoke the inclusion of geothermal in energy policies of other megacities around the world.
CRISPRi mediated Down regulation of SFPQ Gene Expression in Human induced Pluripotent Stem Cells Results in Massive Cell Death
Authors: Lam Navya , Yamanaka Shinya , Perli Samuel
Published: January 2021

CRISPR-Cas9 is widely used for targeted genome editing for a wide range of organisms. In this study, we used CRISPR interference (CRISPRi) which employs a catalytically inactive version of Cas9 (known as Dead Cas9 or dCas9) fused to KRAB a chromatin modifier. Similar to Cas9, the dCas9 protein forms a complex along with single guide RNA (sgRNA) and binds desired DNA sequences in the presence of a protospacer adjacent motif (PAM). However, unlike Cas9, dCas9 doesn’t cleave the DNA sequence but can repress gene expression when fused with KRAB. The role of paraspeckles in human cell biology is relatively unknown. In this study, we used CRISPRi to investigate the role of splicing factor proline and glutamine rich (SFPQ), also known as PSF (PTB-associated splicing factor), which is a conserved and core component of paraspeckles. We designed and constructed six different sgRNAs to target different locations of the SFPQ gene in Human induced Pluripotent Stem Cells (HiPSCs). The most effective sgRNA (sgRNA #5) knocked down the expression of SFPQ up to > 99%. We also observed that the knockdown of SFPQ exhibits severe cell-death phenotype in HiPSCs. This finding suggests that CRISPRi based SFPQ repression can modulate stem cell proliferation and maintenance. This study also suggests that SFPQ could play a vital role in proliferating cells such as cancer cells. Most importantly, these results are significant because in mice, knocking out another core component of paraspeckles results in no apparent phenotype despite the complete loss of paraspeckles. Given that traditional drug testing approaches rely on animal models, it is consequential to consider that human cell biology is more distinct than previously imagined. This study provides a new insight for role and function of SFPQ in iPSCs.
Cationic Nanostructures for the Treatment of Inflammatory Bone Loss
Authors: Huang Hanyao , Pan Weiyi , Wang Yi-Fan , Kim Hyesung , Shao Dan , Huang Baoding , Ho Tzu-Chieh , Lao Yeh-Hsing , Quek Chai Hoon , Shi Jiayu , Shi Bing , Zhang Sheng-Min , Zhao Lei , Leong Kam W.
Published: January 2021

Periodontitis is a common type of inflammatory bone loss and is a risk factor for systemic diseases. The pathogenesis of periodontitis relies on inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. Here we demonstrate that cell-free DNA (cfDNA) is correlated with periodontitis in patient samples, and that cfDNA/TLR9 interactions participate in the immune response of periodontitis. We then tested the hypothesis that removing cfDNA would benefit periodontitis treatment. To create nucleic acid-binding nanoparticles (NABNs) specific for periodontitis, we coated bone-mimicking selenium-doped hydroxyapatite nanoparticles with cationic polyamidoamine dendrimers (PAMAM-G3), and compared the activities of these NABNs with those of soluble PAMAM-G3 polymers. Both NABNs and PAMAM-G3 inhibited periodontitis-related inflammation in vitro by scavenging cfDNA, and alleviated inflammatory bone loss in a mouse model of ligature-induced periodontitis. Both cfDNA scavengers also regulated the mononuclear phagocyte system in a periodontitis environment, promoting the M1 over the M2 macrophage phenotype. However, NABNs showed greater therapeutic effects than PAMAM-G3 in terms of scavenging and reducing inflammation and bone loss in vivo. Our findings demonstrate the importance of cfDNA in periodontitis and the potential for using cfDNA-scavenging and hydroxyapatite-based NABNs to ameliorate inflammation and bone loss in periodontitis.
Gene Regulatory Network Analysis Defines Transcriptome Landscape with Alternative Splicing of Human Umbilical Vein Endothelial Cells during Replicative Senescence
Authors: Ohori Momoko , Nakayama Yusuke , Shimizu-Ogasawara Mari , Toyoshiba Hiroyoshi , Nakanishi Atsushi , Aparicio Samuel , Araki Shinsuke
Published: January 2021

BackgroundEndothelial cell senescence is the state of permanent cell cycle arrest and plays a critical role in the pathogenesis of age-related diseases. However, a comprehensive understanding of the gene regulatory network, including genome-wide alternative splicing machinery, involved in endothelial cell senescence is lacking.ResultsWe thoroughly described the transcriptome landscape of replicative senescent human umbilical vein endothelial cells. Genes showing a monotonic increase or decrease in expression with the culture period were defined as hub genes in the co-expression network. Computational network analysis of these genes led to the identification of canonical and non-canonical senescence pathways, such as MYC and SIRT2 signaling, which were down-regulated in metabolism and chromosome organization processes pathways. Additionally, we showed that endothelial cell senescence involves alternative splicing. Importantly, the first and last exon types of splicing, as observed in FLT1 and ACACA, were preferentially altered among the alternatively spliced genes during endothelial senescence. We further identified novel microexons in PRUNE2 and PSAP, each containing 9 nt, which were altered within the specific domain during endothelial senescence.ConclusionsThese findings unveil the comprehensive transcriptome pathway and novel signaling regulated by RNA processing, including gene expression and splicing, in replicative endothelial senescence.
Determinants of Oral Health Behaviour Among Community Health Workers in Kottayam- A Cross-Sectional Study
Authors: P Najmunnisa K , Thomas Susan Thomas , Gomez Mary Shimi S , James Jesline Merly , Narayan Vivek
Published: January 2021

BackgroundBeliefs and attitudes of community health workers affect their oral health behaviour and knowledge which in turn affects their potential to motivate the public to undertake preventive oral health measures. This study was performed to assess knowledge, attitude, and practices as well as determinants of oral health behaviour among community health workers in rural regions of Kerala.MethodsA cross-sectional study was conducted among 123 community healthcare workers at primary health centres in the Ettumanoor block zone, Kottayam. A two-stage cluster sampling method was used. Data regarding knowledge, attitude, and practice of oral health were acquired through self-administered questionnaires and analyzed using SPSS software version 25. Statistical association between responses in different group of health workers were determined by using Chi-square test. Independent t-test and ANOVA were used to test the difference in attitude and knowledge scores. Bivariate and multivariate regression analyses were applied to identify factors associated with the oral health behaviour of community health workers.ResultsAbout 65% of the participants exhibited poor oral health behaviour. A positive attitude has a significant relation with oral health behaviour status of the participants (p=0.003). Community health workers who attended an oral health education program had a better oral health behaviour status when compared to those who had not attended (p=0.006). Conclusions﻿The results emphasize that oral health education should be given to all the community health workers to enhance their awareness about preventive oral health care.
Appendicitis During the COVID-19 Pandemic: Lessons Learnt From a District General Hospital
Authors: Pringle Heather Caroline Mitchell , Donigiewicz Urszula , Bennett Melissa-Rose , Walker Eleanor , Fowler George , Narang Sunil , Ball Susan , Bethune Robert Mackenzie
Published: January 2021

BackgroundThe COVID-19 pandemic dramatically influenced the delivery of healthcare. In line with the UK Royal Colleges’ advice the management of acute appendicitis (AA) changed with greater consideration for non-operative management (NOM) or open appendicectomy when operative management (OM) was sought. We describe our experience of the presentation, management and outcomes for these patients to inform care for future viral pandemics. MethodsThis retrospective, cohort study compared patients diagnosed with AA between March and July 2019 with those during the pandemic period of March to July 2020. Medical records were reviewed to obtain demographics, inflammatory markers, imaging, severity, management, histology, length of stay (LOS) and 90-day outcomes. ResultsThere were 149 and 125 patients in the 2019 and 2020 cohorts respectively. 14 patients (9.4%) had NOM in 2019 versus 31 (24.8%) in 2020 (p = 0.001). In the 2019 operative management (OM) group 125 patients (92.6%) had laparoscopic appendicectomy versus 65 (69.1%) in 2020. 59 patients (39.6%) had a CT in 2019 versus 70 (56%) in 2020. The median LOS was 4 days in 2019 and 3 days in 2020 (p=0.03). Two patients in each year who received NOM had treatment failure (14.3% in 2019 and 6.5% in 2020). Three patients in 2019 who received OM had treatment failure (2.2%). Of 95 patients tested for COVID-19 all but one tested negative.ConclusionDuring the COVID-19 pandemic there was no observed increase in severity of AA, patients had a shorter LOS and were more likely to have imaging. NOM proportionally increased with no observed change in outcomes.
Coagulation Phenotypes in Sepsis and Effects of Recombinant Human Thrombomodulin: An Analysis of Three Multicenter Observational Studies
Authors: Kudo Daisuke , Goto Tadahiro , Uchimido Ryo , Hayakawa Mineji , Yamakawa Kazuma , Abe Toshikazu , Shiraishi Atsushi , Kushimoto Shigeki
Published: January 2021

Background: A recent randomized trial showed that recombinant thrombomodulin did not benefit patients who had sepsis with coagulopathy and organ dysfunction, suggesting that the effects of thrombomodulin are heterogeneous across sepsis phenotypes. We examined the latent phenotypes of sepsis with coagulopathy and the associations between thrombomodulin treatment and 28-day and in-hospital mortality for each phenotype.Methods: This was a secondary analysis of multicenter registries containing data on adult patients (aged ≥16 years) who were admitted to intensive care units for severe sepsis or septic shock in Japan. Three multicenter registries were divided into derivation (two registries) and validation (one registry) cohorts. Phenotypes were derived using k-means with coagulation markers, platelet counts, prothrombin time/international normalized ratios, fibrinogen, fibrinogen/fibrin-degradation-products (FDP), D-dimer, and antithrombin activities. Associations between thrombomodulin treatment and survival outcomes (28-day and in-hospital mortality) were assessed in derived clusters using a generalized estimating equation.Results: Four sepsis phenotypes were derived from 3,694 patients in the derivation cohort. Cluster dA (n = 323) had severe coagulopathy with high FDP and D-dimer levels, severe organ dysfunction, and high mortality. Cluster dB had severe disease with moderate coagulopathy. Clusters dC and dD had moderate and mild disease with and without coagulopathy, respectively. Thrombomodulin was associated with a lower 28-day (adjusted risk difference [RD]: −17.8% [95% CI −28.7% to −6.9%]) and in-hospital (adjusted RD: −17.7% [95% CI −27.6 to −7.8%]) mortality only in cluster dA. Sepsis phenotypes were similar in the validation cohort, and thrombomodulin treatment was also associated with lower 28-day (RD: −24.9% [95%CI ­−49.1% to −0.7%]) and in-hospital mortality (RD: −30.9% [95%CI ­−55.3 to −6.6%]).Conclusions: We identified four coagulation marker-based sepsis phenotypes. The treatment effects of thrombomodulin varied across sepsis phenotypes. This finding will facilitate future trials of thrombomodulin, in which a sepsis phenotype with high FDP and D-dimer can be targeted.
Adrenocortical Adenoma With Myelolipomatous Metaplasia as a Diagnostic Pitfall: A Case Report and Review of the Literature
Authors: Anbardar Mohammad Hossein , Soleimani Neda , Nikeghbalian Saman , Mohebbi Maryam
Published: January 2021

BackgroundAdrenal incidentalomas are often found during investigation for another tumor or unrelated problems. Except for adrenal myelolipoma (second most common primary adrenal incidentaloma following adrenocortical adenomas), adrenal lipomatous tumors are uncommon generally and are often described as case reports in the literature. Since the amount of fat is variable, without the help of advanced imaging techniques, some adrenal lipomatous tumors may be misdiagnosed before pathologic examination. Herein, we report a case of adrenal adenoma with myelolipomatous metaplasia which was excised as a periceliac mass in the setting of recurrent pancreatic cyst.Case reportA 45-year-old woman with hypertension and end stage renal disease presented with recurrence of a pancreatic cyst (previous pathologic report was mucinous cyst adenoma). During exploratory laparatomy, the mentioned pancreatic cyst was tightly attached to the stomach and jejunum. There was also a periceliac round rubbery lesion(firstly diagnosed by endoscopic ultrasound) which was excised for ruling out malignancy. Histologic examination of the periceliac mass was found to be adrenocortical adenoma with foci of myelolipomatous metaplasia. The pancreatic cyst histology was just a pseudocyst.ConclusionOur case highlights the significance of complete evaluation of incidental findings before surgical intervention, even in the setting of another primary tumor. Myelolipoma and myelolipomatous change (metaplasia) are two different entities. Although very similar as to pathogenesis, there are still some differences.
Primary Giant Cell Tumor of the Axis: a Case Report
Authors: Wang Peng , Song Chunhao , Chen Cong , Liu Bo , Jia Jun , Chu Xiangquan
Published: January 2021

Background: Primary giant cell tumor of the axis is a rare. The authors reported a case of a primary giant cell tumor of the axis revealed by cervical pain, and discussed the diagnosis and treatment of giant cell tumor.Case presentation: The patient presented to our clinic with neck pain and unstable gait. X-ray, computed tomography and magnetic resonance imaging showed osteolysis of the body and vertebral arch of the axis. Histologic evaluation gave a conclusion of a giant tumor, grade II. Spondylectomy of the axis was performed by the transoral approach. The local recurrence of the tumor was found 3 months later and the patient refused further therapy.Conclusion: Primary giant cell tumor of the axis is a rare type tumor with poor prognosis. Definitive diagnosis should be based on histopathological morphology and surgical treatment should be performed as soon as possible.