bluuebunny/crossref_metadata_2025 huggingface dataset:
Ubiquitin ligase RIPLET mediates polyubiquitination of RIG-I and LGP2 and regulates the innate immune responses to SARS-CoV-2 infection
Authors: Kouwaki Takahisa , Nishimura Tasuku , Wang Guanming , Nakagawa Reiko , Oshiumi Hiroyuki
Published: January 2021

RIG-I, a cytoplasmic viral RNA sensor, is crucial for innate antiviral immune responses; however, there are controversies about RIG-I’s regulatory mechanism by several ubiquitin ligases and LGP2. Our genetic study revealed that the RIPLET ubiquitin ligase was a general activating factor for RIG-I signaling, whereas another ubiquitin ligase, TRIM25, activated RIG-I in a cell-type-specific manner. These RIPLET and TRIM25 functions were modulated by accessory factors, such as ZCCH3C and NLRP12. Interestingly, we found an additional role of RIPLET in innate immune responses. RIPLET induced delayed polyubiquitination of LGP, resulting in the attenuation of excessive cytokine expression at the late phase. Moreover, RIPLET was involved in the innate immune responses against SARS-CoV-2 infection, a cause of the recent COVID-19 pandemic. Our data indicate that RIPLET fine-tunes innate immune responses via polyubiquitination of RIG-I and LGP2 against virus infection, including SARS-CoV-2.
Commitment to inclusion: a review of SEND provision across mainstream secondary schools in Southampton
Authors: Belli Clare
Published: January 2021

This short piece of action research seeks to identify the strengths of secondary school provision for students with SEND, in order to provide a city wide overview in which good practice and expertise can be shared. It also considers the particular barriers faced by secondary schools and examines how schools are working to overcome these barriers. The research suggests that despite the challenges of reduced funding, some schools are developing innovative ways to maximise resources and provide flexible pathways of provision for pupils with SEND. These include establishing a graduated approach to support with clear mechanisms for early identification of need, ongoing monitoring of progress and robust systems for self‐evaluation leading to school improvement. In addition, some schools have sought to design a modified and enhanced curriculum for more vulnerable students, with flexible access to short‐term interventions and alternative provision. However, there is evidence to suggest that an emphasis on summative attainment data with a lack of specificity around target setting, sometimes leaves pupils unclear about the progress they are making and what they need to do to improve. The research suggests that schools should consider how a vision for SEND needs to be driven by senior leadership teams and how the role of the SENCo can be strengthened by adopting the principles of distributed leadership to bring about collective influence. Consideration of how schools can work together to share expertise and develop structured opportunities for continuous professional development, could help to secure positive outcomes for pupils with SEND and create long‐term sustainability.
The Chief Rabbinate and Israel's Independence Day Religio‐National Rituals During the 1950s†
Authors: Sherzer Adi
Published: January 2021

This article investigates the place of the Israeli Chief Rabbinate in the formation of Israel's national symbolic language during the country's first Independence Days. My main argument is that, like other state churches, the Rabbinate act as an important agent of memory that imparts collective myths and authenticate them. However, the Rabbinate was not willing to fully integrate the new national stance into the traditional ritual language and was therefore criticised accordingly. This criticism, and the alternative rituals it gave rise to, shows that certain circles of Israeli society were willing to go much further with the integration of national components into the traditional Jewish world. In addition, it demonstrates the necessity of the public's “approval” of the ritual, and therefore reveals the limits of memory agents. The first section of the article presents the background for the religious observance of the national holiday, the second section illustrates the nature of the first Independence Day synagogue services, the third section describes the criticism they had provoked, and the fourth section analyses the alternative rituals held on Mount Zion and the radical religious‐national integration they created. Finally, the conclusion seeks to place this case within the wider context of nation‐building and its religious aspects.
Microbial community dynamics of fermented kefir beverages changes over time
Authors: de Almeida Brasiel Poliana Guiomar , Dutra Medeiros Julliane , Barbosa Ferreira Machado Alessandra , Schuchter Ferreira Maíra , Gouveia Peluzio Maria do Carmo , Potente Dutra Luquetti Sheila Cristina
Published: January 2021

Kefir is a traditional fermented milk associated with several health benefits, such as immune system modulation, as well as antimicrobial, antitumor and antioxidant activity. The aim of the current study was to investigate the microbial dynamics of kefir production based on high‐throughput DNA sequencing. Results of sequence analysis have grouped the reads into 303 and 112 amplicon sequence variants (ASV) for bacteria and fungi, respectively. Firmicutes, Bacteroidetes and Proteobacteria were the prevalent bacterial phyla, whereas Lactococcus was the prevalent bacterial genus. Ascomycota was the main fungal phylum. Data have shown heterogeneity in diversity and abundance distributions between milk kefir samples.
Identifying outlier patterns of inconsistent ambulance billing in Medicare
Authors: Sanghavi Prachi , Jena Anupam B. , Newhouse Joseph P. , Zaslavsky Alan M.
Published: January 2021

Objective

To illustrate a method that accounts for sampling variation in identifying suppliers and counties with outlying rates of a particular pattern of inconsistent billing for ambulance services to Medicare.

Data Sources

US Medicare claims for a 20% simple random sample of 2010‐2014 fee‐for‐service beneficiaries.

Study Design

We identified instances in which ambulance suppliers billed Medicare for transporting a patient to a hospital, but no corresponding hospital visit appeared in billing claims. We estimated the distributions of outlier supplier and county rates of such “ghost rides” by fitting a nonparametric empirical Bayes model with flexible distributional assumptions to account for sampling variation.

Data Collection

We included Basic and advanced life support ground emergency ambulance claims with a hospital destination.

Principal Findings

“Ghost ride” rates varied considerably across both ambulance suppliers and counties. We estimated 6.1% of suppliers and 5.0% of counties had rates that exceeded 3.6%, which was twice the national average of “ghost rides” (1.8% of all ambulance transports).

Conclusions

Health care fraud and abuse are frequently asserted but can be difficult to detect. Our data‐driven approach may be a useful starting point for further investigation.
Probiotic Lactobacillus casei Shirota prevents acute liver injury by reshaping the gut microbiota to alleviate excessive inflammation and metabolic disorders
Authors: Yan Ren , Wang Kaicen , Wang Qiangqiang , Jiang Huiyong , Lu Yingfeng , Chen Xiaoxiao , Zhang Hua , Su Xiaoling , Du Yiling , Chen Lifeng , Li Lanjuan , Lv Longxian
Published: January 2021

Millions of people die from liver diseases annually, and liver failure is one of the three major outcomes of liver disease. The gut microbiota plays a crucial role in liver diseases. This study aimed to explore the effects of Lactobacillus casei strain Shirota (LcS), a probiotics used widely around the world, on acute liver injury (ALI), as well as the underlying mechanism. Sprague Dawley rats were intragastrically administered LcS suspensions or placebo once daily for 7 days before induction of ALI by intraperitoneal injection of D‐galactosamine (D‐GalN). Histopathological examination and assessments of liver biochemical markers, inflammatory cytokines, and the gut microbiota, metabolome and transcriptome were conducted. Our results showed that pretreatment with LcS reduced hepatic and intestinal damage and reduced the elevation of serum gamma‐glutamyltranspeptidase (GGT), total bile acids, IL‐5, IL‐10, G‐CSF and RANTES. The analysis of the gut microbiota, metabolome and transcriptome showed that LcS lowered the ratio of Firmicutes to Bacteroidetes; reduced the enrichment of metabolites such as chenodeoxycholic acid, deoxycholic acid, lithocholic acid, d‐talose and N‐acetyl‐glucosamine, reduce the depletion of d‐glucose and l‐methionine; and alleviated the downregulation of retinol metabolism and PPAR signalling and the upregulation of the pyruvate metabolism pathway in the liver. These results indicate the promising prospect of using LcS for the treatment of liver diseases, particularly ALI.
An unusual overrepresentation of genetic factors related to iron homeostasis in the genome of the fluorescent Pseudomonas sp. ABC1
Authors: Valenzuela‐Heredia Daniel , Henríquez‐Castillo Carlos , Donoso Raúl , Lavín Paris , Ringel Michael T. , Brüser Thomas , Campos José Luis
Published: January 2021

Members of the genus Pseudomonas inhabit diverse environments, such as soil, water, plants and humans. The variability of habitats is reflected in the diversity of the structure and composition of their genomes. This cosmopolitan bacterial genus includes species of biotechnological, medical and environmental importance. In this study, we report on the most relevant genomic characteristics of Pseudomonas sp. strain ABC1, a siderophore‐producing fluorescent strain recently isolated from soil. Phylogenomic analyses revealed that this strain corresponds to a novel species forming a sister clade of the recently proposed Pseudomonas kirkiae. The genomic information reveals an overrepresented repertoire of mechanisms to hoard iron when compared to related strains, including a high representation of fecI‐fecR family genes related to iron regulation and acquisition. The genome of the Pseudomonas sp. ABC1 contains the genes for non‐ribosomal peptide synthetases (NRPSs) of a novel putative Azotobacter‐related pyoverdine‐type siderophore, a yersiniabactin‐type siderophore and an antimicrobial betalactone; the last two are found only in a limited number of Pseudomonas genomes. Strain ABC1 can produce siderophores in a low‐cost medium, and the supernatants from cultures of this strain promote plant growth, highlighting their biotechnological potential as a sustainable industrial microorganism.
Deep brain stimulation versus ablative surgery for treatment‐refractory obsessive‐compulsive disorder: A meta‐analysis
Authors: Hageman Sarah Babette , van Rooijen Geeske , Bergfeld Isidoor O. , Schirmbeck Frederike , de Koning Pelle , Schuurman P. Rick , Denys Damiaan
Published: January 2021

Objective

Ablative surgery (ABL) and deep brain stimulation (DBS) are last‐resort treatment options for patients suffering from treatment‐refractory obsessive‐compulsive disorder (OCD). The aim of this study was to conduct an updated meta‐analysis comparing the clinical outcomes of the ablative procedures capsulotomy and cingulotomy and deep brain stimulation.

Methods

We conducted a PubMed search to identify all clinical trials on capsulotomy, cingulotomy, and DBS. Random effects meta‐analyses were performed on 38 articles with a primary focus on efficacy in reducing OCD symptoms as measured by a reduction in the Yale‐Brown Obsessive‐Compulsive Scale (Y‐BOCS) score and the responder rate (≥35% reduction in Y‐BOCS score).

Results

With responder rates of 48% and 53% after 12–16 months and 56% and 57% at last follow‐up for ABL and DBS, respectively, and large effect sizes in the reduction in Y‐BOCS scores, both surgical modalities show effectiveness in treating refractory OCD. Meta‐regression did not show a statistically significant difference between ABL and DBS regarding these outcomes. Regarding adverse events, a statistically significant higher rate of impulsivity is reported in studies on DBS.

Conclusion

This meta‐analysis shows equal efficacy of ABL and DBS in the treatment of refractory OCD. For now, the choice of intervention should, therefore, rely on factors such as risk of developing impulsivity, patient preferences, and experiences of psychiatrist and neurosurgeon. Future research should provide more insight regarding differences between ABL and DBS and response prediction following direct comparisons between the surgical modalities, to enable personalized and legitimate choices between ABL and DBS.
Paradoxical effect of SARS‐CoV‐2 infection in patients with immune thrombocytopenia
Authors: de la Cruz‐Benito Beatriz , Rivas‐Pollmar María I. , Álvarez Román María T. , Trelles‐Martínez Roberto , Martín‐Salces Monica , Lázaro‐del Campo Paula , Ramírez‐López Andrés , García‐Barcenilla Sara , Cebanu Tamara , Acuña‐Butta Paula , Monzón‐Manzano Elena , González‐Zorrilla Elena , Jiménez‐Yuste Victor , Butta Nora V.
Published: January 2021

Thrombocytopenia has been identified as a common complication of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection in the general population. In an attempt to determine the impact of coronavirus disease 2019 (COVID‐19) in patients with immune thrombocytopenia (ITP), a retrospective single‐centre study was performed. Thrombocytosis was observed in patients with chronic ITP after SARS‐CoV‐2 infection, frequently needing treatment adjustment or even discontinuation of therapy. Relapses and newly diagnosed cases showed a fast response after initial treatment compared to ITP. Reduced immune activity due to lymphopenia during COVID‐19 could explain this paradoxical effect, although further studies are needed.
Efficacy of parthenium hysterophorus waste biomass compared with activated charcoal for the removal of CI Reactive Red 239 textile dye from wastewater
Authors: Bapat Shreyas , Jaspal Dipika , Malviya Arti
Published: January 2021

In the quest to find an eco‐friendly, cost‐effective and efficient alternative to expensive and non‐biodegradable activated charcoal (AC), in the current study the potential of a weed, parthenium hysterophorus (PH), has been explored as a bio‐adsorbent for purification of textile wastewater. Root, stem and leaves of PH weed have been used as bio‐adsorbents in raw and surface‐treated forms and compared with AC for removal of toxic textile dye CI Reactive Red 239 (Remazol Brilliant Red 3BS [RBR 3BS]) from wastewater. The surface treatment carried out using QAS (N‐Cetyl‐N,N,N–trimethylammonium bromide) in the current study is a novel way to enhance the dye adsorption capacity of raw adsorbents of PH. Characterisation tools like Fourier Transform–infrared spectroscopy, scanning electron microscopy, elemental analysis and potential of zero charge have been used to confirm the surface treatment. The impact of various process variables like pH, dosage of adsorbent, contact time, solution temperature and dye concentration have been studied. Isothermal, kinetic and thermodynamics modelling for adsorption data have been thoroughly investigated to ascertain the mechanism of adsorption. Statistical error functions like root mean square error, chi‐square test, sum of absolute error and normalized standard deviation (NSD) have been used to validate the adsorption data. Results revealed that novel surface treatment significantly improved the dye adsorption capacity of raw PH adsorbents (ca. 15‐16 times). Of all the weed bio‐adsorbents, surface‐treated PH stem showed the highest dye adsorption capacity (105 mg/g), which was 10‐folds greater than commercial grade AC (10.4 mg/g at 27°C). For both adsorbents, surface‐treated PH stem and AC, adsorption followed pseudo‐second order kinetics, and the Langmuir isotherm was the best fit with film diffusion as a rate‐controlling step. Thermodynamic parameters infer the spontaneous and exothermic nature of adsorption. Therefore, in the current study, surface‐treated PH stem bio‐adsorbent has been revealed as a superior alternative to AC for the removal of RBR 3BS dye from wastewater, opening a new gateway to the utilisation of waste weeds for the purpose of wastewater treatment.
Population pharmacokinetic and exposure‐response analyses of ivosidenib in patients with IDH1‐mutant advanced hematologic malignancies
Authors: Jiang Xuemin , Wada Russ , Poland Bill , Kleijn Huub Jan , Fan Bin , Liu Guowen , Liu Hua , Kapsalis Stephanie , Yang Hua , Le Kha
Published: January 2021

Ivosidenib is a once daily (q.d.), orally available, potent mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor approved for treatment of patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and intensive chemotherapy ineligible AML with a susceptible IDH1 mutation. Population pharmacokinetics (PKs; N = 253), exposure‐response (efficacy [n = 201] and safety [n = 253]), and concentration‐corrected electrocardiogram QT interval (QTc; n = 171) analyses were performed using phase I data (100 mg twice daily and 300–1200 mg q.d.). Ivosidenib disposition was well‐described by a two‐compartment PK model with first‐order absorption and elimination. Between‐subject variability was moderate for PK parameters. Intrinsic factors did not affect ivosidenib PKs. Moderate/strong CYP3A4 inhibitors increased the area under the plasma ivosidenib concentration‐time curve at steady state (AUCss) by 60%. Efficacy responders and nonresponders had similar ivosidenib exposures. Based on AUCss, there was no apparent relationship between ivosidenib exposure and efficacy or adverse events. The plasma ivosidenib concentration‐QT analysis showed a mean change in QTc using Fridericia’s method (ΔQTcF) of 17.2 msec at the approved 500 mg q.d. dose. Because of the direct association between ivosidenib exposure and QTcF, patients should have their electrocardiograms and electrolytes monitored, and comedications that increase ivosidenib exposure or prolong the QT interval should be avoided. These model‐based analyses quantitatively provide a framework to describe the relationship among ivosidenib dose, exposure, and clinical end points. With precautions for QTc prolongation, the exposure‐response analyses support the 500 mg q.d. dose in patients with AML with a susceptible IDH1 mutation.
Vergleich der Wirksamkeit und Sicherheit von Biologika bei mittelstark bis stark ausgeprägter Plaque‐Psoriasis: Metaanalyse multipler Therapien
Authors: Xu Shanshan , Gao Xing , Deng Jixiang , Yang Jiajia , Pan Faming
Published: January 2021

Ziel

Vergleich der Wirksamkeit und Sicherheit von Biologika bei Patienten mit mittelstark bis stark ausgeprägter Plaque‐Psoriasis.

Methoden

Systematische Auswertung von 60 randomisierten, kontrollierten Studien mit insgesamt 34 020 Teilnehmern, in denen 14 Biologika zur Behandlung der mittelstark bis stark ausgeprägten Plaque‐Psoriasis verglichen wurden. Die Hauptkriterien in der Analyse waren eine Verminderung des Schweregrades im Psoriasis Area and Severity Index um ≥ 90 % (PASI 90) sowie die Anzahl der Patienten, die unter der Behandlung aufgetretene Nebenwirkungen (NW) berichteten. Sekundäre Kriterien waren ≥ 75 % Verminderungen im Psoriasis Area and Severity Index (PASI 75), ein Physician’s Global Assessment von 0/1 (PGA 0/1) sowie Infektionen.

Ergebnisse

Diese Netzwerk‐Metaanalyse zeigt, dass Biologika signifikant wirksamer sind als Placebo. Ixekizumab, Risankizumab und Bimekizumab gehören zu den wirksamsten Behandlungsmöglichkeiten, während Tildrakizumab, Guselkumab und Risankizumab den anderen Arzneimitteln in der Sicherheit überlegen sind. Risankizumab und Guselkumab zeigten sowohl in der Wirksamkeit als auch in der Sicherheit stabile Ergebnisse. Betrachtet man die unterschiedlichen Wirkstoffklassen, dann erweisen sich die Interleukin (IL)‐17A‐Hemmer als besonders wirksam und die Hemmstoffe der p19‐Untereinheit des IL‐23 unter allen wirksamen Biologika als am besten verträglich.

Schlussfolgerungen

Ixekizumab zeigte sich im PASI 90 als die wirksamste Substanz, während die IL‐23p19‐Hemmstoffe Risankizumab und Guselkumab sowohl in der Wirksamkeit als auch in der Sicherheit relativ stabile Ergebnisse erbrachten.
Comparison of patient pathways in the early detection of skin cancer – a claims data analysis
Authors: Krensel Magdalene , Petersen Jana , Stephan Brigitte , Katalinic Alexander , Augustin Jobst
Published: January 2021

Background

Regarding skin cancer screening, patients in Germany have the choice between a direct screening by dermatologists or an initial screening by general practitioners followed by dermatological screening if further examination is required. The aim of this study is to evaluate whether screening by general practitioners is associated with risk selection in subsequent dermatological screenings.

Patients and Methods

We conducted a retrospective observational study based on claims data from a German health insurance company (Barmer GEK). Patient pathways in skin cancer screenings between 2008 and 2016 were analyzed, and differences between the two groups were tested at 95 % confidence intervals.

Results

A total of 495,000 initial and 111,000 secondary examinations by dermatologists were analyzed. The proportion of subsequent excisions was lower in initial screenings by dermatologists. To diagnose one person with non‐melanoma skin cancer or melanoma, five or 23 to 42 excisions were necessary, depending on the type of excision considered. The number of examinations to identify one patient ranged from 25 to 53 for non‐melanoma skin cancer and 42 to 165 for melanoma. For melanoma, the number of excisions and screenings to diagnose skin cancer was lower in secondary examinations.

Conclusions

The results indicate a risk selection through initial examinations by general practitioners. However, there are other aspects that should be taken into account when comparing the two pathways.
Large‐scale eDNA metabarcoding survey reveals marine biogeographic break and transitions over tropical north‐western Australia
Authors: West Katrina , Travers Michael J. , Stat Michael , Harvey Euan S. , Richards Zoe T. , DiBattista Joseph D. , Newman Stephen J. , Harry Alastair , Skepper Craig L. , Heydenrych Matthew , Bunce Michael
Published: January 2021

Aim

Environmental DNA (eDNA) metabarcoding has demonstrated its applicability as a highly sensitive biomonitoring tool across small spatial and temporal scales in marine ecosystems. However, it has rarely been tested across large spatial scales or biogeographical barriers. Here, we scale up marine eDNA metabarcoding, test its ability to detect a major marine biogeographic break and evaluate its use as a regional biomonitoring tool in Australia.

Location

North‐western Australia (NWA).

Methods

We applied metabarcoding assays targeting the mitochondrial 16S rRNA and CO1 genes to 284 surface seawater eDNA samples collected from 71 mid‐shelf, inshore, coastal and nearshore estuarine sites over 700 km of the NWA coastline.

Results

Metabarcoding detected a wide range of bony fish (404 taxa), elasmobranchs (44) and aquatic reptiles (5). We detected bioregional and depth differentiation within inshore bony fish communities. These findings support the presence of a marine biogeographic break, which is purported to occur in the vicinity of Cape Leveque, demarcating the border between the Kimberley and Canning bioregions. Inshore bony fish and elasmobranch communities, as well as coastal bony fish assemblages, were additionally found to differ between the South and North Kimberley regions suggesting previously unrecognized subregional differentiation amongst these taxa. The overall compositional data have been used to update distribution information for a number of endangered, elusive and data‐deficient taxa, including sawfish (family: Pristidae), northern river shark (Glyphis garricki) and wedgefish (genus: Rhynchobatus).

Main conclusions

eDNA metabarcoding demonstrated a high level of sensitivity that was able to discern fine‐scale patterns across the large‐scale, remote and oceanographically complex region of North‐western Australia. Importantly, this study highlights the potential of integrating broad‐scale eDNA metabarcoding alongside other baseline surveys and long‐term monitoring approaches, which are crucial for the sustainable management and conservation of marine biodiversity in this unique marine region.
Formation of a multi‐layered 3‐dimensional structure of the heterochromatin compartment during early mammalian development
Authors: Poonperm Rawin , Hiratani Ichiro
Published: January 2021

During embryogenesis in mammals, the 3‐dimensional (3D) genome organization changes globally in parallel with transcription changes in a cell‐type specific manner. This involves the progressive formation of heterochromatin, the best example of which is the inactive X chromosome (Xi) in females, originally discovered as a compact 3D structure at the nuclear periphery known as the Barr body. The heterochromatin formation on the autosomes and the Xi is tightly associated with the differentiation state and the developmental potential of cells, making it an ideal readout of the cellular epigenetic state. At a glance, the heterochromatin appears to be uniform. However, recent studies are beginning to reveal a more complex picture, with multiple hierarchical levels co‐existing within the heterochromatin compartment. Such hierarchical levels appear to exist in the heterochromatin compartment on autosomes as well as on the Xi. Here, we review recent progress in our understanding of the 3D genome organization changes during the period of differentiation surrounding pluripotency in vivo and in vitro, with a focus on the heterochromatin compartment. We first look at the whole genome, then focus on the Xi, and discuss their differences and similarities. Finally, we present a unified view of how the heterochromatin compartment is formed and regulated during early development. In particular, we emphasize that there are multiple layers within the heterochromatic compartment on both the autosomes and the Xi, with regulatory mechanisms common and specific to each layer.
Glucocorticoids for acute respiratory distress syndrome: A systematic review with meta‐analysis and trial sequential analysis
Authors: Junhai Zhen , Bangchuan Hu , Shijin Gong , Jing Yan , Li Li
Published: January 2021

Background

Glucocorticoids are some of the most commonly used drugs for patients with acute respiratory distress syndrome (ARDS). However, the curative effect and side effects of glucocorticoids in treating patients with ARDS remain controversial.

Methods

Three databases were searched until 2 July 2020, and randomized controlled trials (RCTs) that compared glucocorticoids versus other therapies in the treatment of ARDS were included in this meta‐analysis. Trial sequential analysis (TSA) was conducted.

Results

A total of 14 RCTs with 1362 ARDS patients were assessed. Overall, no statistically significant effect was found on mortality between the glucocorticoid group and the control group of ARDS patients. In the subgroup analysis, no benefit of glucocorticoids for ARDS on mortality was found in trials stratified according to low versus high risk of bias or with vs. without a loading dose. As for the dose and length of therapy, no statistically significant effect was found on mortality with high‐dose, short‐course glucocorticoid therapy. However, lower‐dose and longer‐course therapy with glucocorticoids was found to decrease the mortality of ARDS patients (lower dose: RR = 0.69, 95% CI = 0.51‐0.93, P = .02; longer‐course therapy: RR = 0.60, 95% CI = 0.37‐0.99, P = .04). The TSA showed that more trials are needed to confirm the results.

Conclusions

Longer‐ and lower‐dose glucocorticoid treatment may improve the prognosis of ARDS patients, but RCTs with higher quality and larger sample sizes are needed to further clarify the clinical effects of glucocorticoids on ARDS.
ID1 inhibits foot‐and‐mouth disease virus replication via targeting of interferon pathways
Authors: Ren Tingting , Chen Haotai , Liu Xinsheng , Wang Yanxue , Fan Aixia , Qi Linlin , Pan Li , Bai Wenlong , Zhang Yongguang , Sun Yuefeng
Published: January 2021

Inhibitor of DNA‐binding 1 (ID1) protein has been studied intensively for its functions in tumorigenesis and maintenance of stem cell‐like properties, but its roles in virus infection are less understood. In the present study, we have clearly shown that the foot‐and‐mouth disease virus (FMDV) promotes ID1 degradation via Cdh1‐mediated ubiquitination to facilitate its replication. Mechanistic investigations reveal Forkhead Box O1 (FOXO1) as an ID1 partner, which suppresses interferon regulatory factors 3 expression and interferon (IFN) production. Further investigation identified that ID1 suppresses FOXO1 transcription activity through HDAC4‐mediated deacetylation, promoting IFN production and antiviral immune response. These studies establish a prominent role for ID1 in suppressing FDMV replication, which may be extended to other viruses.
The role of task repetition in a Korean as a foreign language classroom: Writing quality, attention to form, and learning of Korean grammar
Authors: Kim YouJin , Kang Sanghee , Yun Hyunae , Kim Binna , Choi Bumyong
Published: January 2021

Task repetition is being increasingly examined in the fields of second language acquisition and task‐based language teaching, and the findings have revealed insightful theoretical and pedagogical implications for foreign language instruction. However, previous research has mainly focused on speaking tasks, and the role of different types of task repetition using collaborative writing tasks has received little attention. This study compared two task repetition types (exact task repetition and procedural repetition) on the quality of writing output (i.e., complexity and accuracy), learner attention to linguistic forms, and the learning of four Korean grammar features. Thirty‐eight Korean‐language learners were assigned to either an exact task repetition or a procedural repetition condition. They completed a pretest, two collaborative writing tasks, and a posttest over two weeks. Written output was analyzed for complexity and accuracy, and learners' oral interactions during collaborative writing were analyzed for the occurrence of language‐related episodes. Pretest and posttest responses were scored for suppliance and accuracy of target feature production. Results showed that exact task repetition benefitted syntactic complexity and the accuracy of target features. However, little evidence of benefits for global accuracy was found. The procedural repetition group performed less well during the second task performance than they did on the first task. However, they scored significantly higher on the posttest compared to the exact repetition group.
Relationships between health literacy and quality of life among survivors with breast cancer
Authors: Wei Ching‐Wen , Wu Mei‐Lan , Tung Heng‐Hsin
Published: January 2021

Purpose

During the survival period of breast cancer patients, an understanding of and ability to implement health knowledge may be important for survivors' physical and mental quality of life (QOL). This study aims to investigate the health literacy and predictors of QOL for survivors of breast cancer.

Method

A cross‐sectional design was used, and convenience sampling was performed. Eighty‐six survivors with breast cancer were recruited from a general hospital in northern Taiwan from February to August 2017. Taiwan's health literacy scale and SF‐12 questionnaire were used for data collection.

Results

The average health literacy score was 3.28. Education level and breast cancer stage were significant factors for the health literacy of survivors with breast cancer. Age, body mass index and health literacy were predictors of physical health‐related QOL. Health literacy also was a predictor of mental health‐related QOL.

Conclusion

The results provide the factors associated health literacy as well as health‐related QOL. Nurses should understand the health literacy among survivors with breast cancer and improve health literacy to optimize their quality of life.
Electric field assisted solid‐state interfacial joining of TaC‐HfC ceramics without filler
Authors: Nisar Ambreen , Dolmetsch Tyler , Paul Tanaji , Zhang Cheng , Boesl Benjamin , Agarwal Arvind
Published: January 2021

The application of ultra‐high‐temperature ceramics (UHTCs) demands effective ways of joining in overcoming the problems associated with the fabrication of complex‐shaped components. In this study, we choose to investigate a new method of rapidly joining pre‐sintered TaC and HfC ceramics without any filler material using the spark plasma sintering (SPS) technique. A well‐bonded TaC–HfC interface was observed with no apparent cracking and porosity at the joint. The joining mechanisms were predominantly driven by solid‐state diffusion and localized plastic deformation. The nanomechanical properties of the TaC‐HfC joint are better than the HfC while comparable to that of the TaC. High‐load indentation (up to 200 N) results suggest that the TaC–HfC interface is stronger than the parent UHTCs with no crack propagating at the interface. Upon comparison with the parent UHTCs, the damaged area and the average crack length at the interface, reduced up to ~94% and ~56%, respectively. This study shows that the SPS technique can also apply to joining other UHTCs without any filler, resulting in the new field of developing complex components for the thermal protection system (TPS).
Outcomes of two versus three incision techniques: Results from the subcutaneous ICD post‐approval study
Authors: El‐Chami Mikhael , Weiss Raul , Burke Martin C. , Gold Michael R. , Prutkin Jordan M. , Kalahasty Gautham , Shen Sharon , Mirro Michael J. , Carter Nathan , Aasbo Johan D.
Published: January 2021

Background

Traditionally, implantation of the subcutaneous implantable cardioverter defibrillator (S‐ICD) requires incisions near the lateral chest wall, the xyphoid, and the superior sternal region (three‐incision technique [3IT]). A two‐incision technique (2IT) avoids the superior incision and has been shown to be a viable alternative in small studies with limited follow‐up.

Objectives

To report on the long‐term safety and efficacy of the 2IT compared to the 3IT procedure in a large patient cohort.

Methods

Patients enrolled in the S‐ICD post approval study (PAS) were stratified by procedural technique (2IT vs. 3IT). Baseline demographics, comorbidities and procedural outcomes were collected. Complications and S‐ICD effectiveness in treating ventricular arrhythmias through an average 3‐year follow‐up period were compared.

Results

Of 1637 patients enrolled in the S‐ICD PAS, 854 pts (52.2%) were implanted using the 2IT and 782 were implanted using the 3IT (47.8%). The 2IT became more prevalent over time, increasing from 40% to 69% of implants (Q1–Q4). Mean procedure time was shorter with 2IT (69.0 vs. 86.3 min, p < .0001). No other differences in outcomes were observed between the two groups, including rates of infection, electrode migration, inappropriate shocks and first shock efficacy for treating ventricular arrhythmias.

Conclusion

In this large cohort of patients implanted with an S‐ICD and followed for 3 years the 2IT was as safe and effective as the 3IT while significantly reducing procedure time.
Interactions between hypertension and inflammatory tone and the effect on blood pressure and outcomes in patients with COVID‐19
Authors: Amar Jacques , Touront Nicolas , Ciron Antoine M. , Pendaries Caroline
Published: January 2021

Arterial hypertension represented one of the most common comorbidities in patients with COVID‐19. However, the impact of hypertension on outcome in COVID‐19 patients is not clear. Close connections between inflammation and blood pressure (BP) have been described, and inflammation plays a key role in the outcome for patients with COVID‐19. Whether hypertension impairs the relationship between inflammation, BP, and outcomes in this context is not known. The aim of this study was to examine the effects of the interactions between inflammation and hypertension status on BP and clinical outcome in patients hospitalized with COVID‐19. We designed a retrospective study in 129 patients hospitalized with COVID‐19 at Toulouse University Hospital. The hospital outcome was admission to the intensive care unit or death. The inflammatory markers were blood C‐reactive protein level (CRP), neutrophil to lymphocyte, and platelet to lymphocyte ratios. We identified strong correlations between CRP (P < .01) and the other inflammatory markers recorded on admission (P < .001) with mean BP within 3 days after admission in normotensive patients, whereas these correlations were absent in patients with hypertension. Also, we observed after multivariate adjustment (P < .05) that CRP level predicted a worse prognosis in hypertensive patients (relative risk 2.52; 95% confidence intervals [1.03‐ 6.17]; P = .04), whereas CRP was not predictive of outcome in patients without hypertension. In conclusion, the study revealed that in COVID‐19 patients, hypertension impairs the relationship between inflammation and BP and interacts with inflammation to affect prognosis. These findings provide insights that could explain the relationship between hypertension and outcomes in COVID‐19 patients.
Effect of angiotensin receptor blockers on the development of cancer: A nationwide cohort study in korea
Authors: Jung Mi‐Hyang , Lee Ju‐Hee , Lee Chan Joo , Shin Jeong‐Hun , Kang Si Hyuck , Kwon Chang Hee , Kim Dae‐Hee , Kim Woo‐hyeun , Kim Hack Lyoung , Kim Hyue Mee , Cho In Jeong , Cho Iksung , Hwang Jinseub , Ryu Soorack , Kang Chaeyeong , Lee Hae‐Young , Chung Wook‐Jin , Ihm Sang‐Hyun , Kim Kwang Il , Cho Eun Joo , Sohn Il‐Suk , Park Sungha , Shin Jinho , Ryu Sung Kee , Rhee Moo‐Yong , Kang Seok‐Min , Pyun Wook Bum , Cho Myeong‐Chan , Sung Ki‐Chul
Published: January 2021

The potential cancer risk associated with long‐term exposure to angiotensin receptor blockers (ARBs) is still unclear. We assessed the risk of incident cancer among hypertensive patients who were treated with ARBs compared with patients exposed to angiotensin‐converting enzyme inhibitors (ACEIs), which are known to have a neutral effect on cancer development. Using the Korean National Health Insurance Service database, we analyzed the data of patients diagnosed with essential hypertension from January 2005 to December 2012 who were aged ≥40 years, initially free of cancer, and were prescribed either ACEI or ARB (n = 293,962). Cox proportional hazard model adjusted for covariates was used to evaluate the risk of incident cancer. During a mean follow‐up of 10 years, 24,610 incident cancers were observed. ARB use was associated with a decreased risk of overall cancer compared with ACEI use (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.72‐0.80). Similar results were obtained for lung (HR 0.73, 95% CI 0.64‐0.82), hepatic (HR 0.56, 95% CI 0.48‐0.65), and gastric cancers (HR 0.74, 95% CI 0.66‐0.83). Regardless of the subgroup, greater reduction of cancer risk was seen among patients treated with ARB than that among patients treated with ACEIs. Particularly, the decreased risk of cancer among ARB users was more prominent among males and heavy drinkers (interaction P < .005). Dose‐response analyses demonstrated a gradual decrease in risk with prolonged ARB therapy than that with ACEI use. In conclusion, ARB use was associated with a decreased risk of overall cancer and several site‐specific cancers.
Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT‐20 cells
Authors: Xia Liqun , Shen Danyang , Zhang Youyun , Lu Jieyang , Wang Mingchao , Wang Huan , Chen Yuanlei , Xue Dingwei , Xie Dajiang , Li Gonghui
Published: January 2021

Drug options for the life‐threatening Cushing's disease are limited, and surgical resection or radiation therapy is not invariably effective. Testicular receptor 4 (TR4) has been identified as a novel drug target to treat Cushing's disease. We built the structure model of TR4 and searched the TR4 antagonist candidate via in silico virtual screening. Bexarotene was identified as an antagonist of TR4 that can directly interact with TR4 ligand binding domain (TR4‐LBD) and induces a conformational change in the secondary structure of TR4‐LBD. Bexarotene suppressed AtT‐20 cell growth, proopiomelanocortin (POMC) expression and adrenocorticotropin (ACTH) secretion. Mechanism dissection revealed that bexarotene could suppress TR4‐increased POMC expression via promoting the TR4 translocation from the nucleus to the cytoplasm. This TR4 translocation might then result in reducing the TR4 binding to the TR4 response element (TR4RE) on the 5’ promoter region of POMC. Results from in vivo mouse model also revealed that oral bexarotene administration markedly suppressed ACTH‐secreting tumour growth, adrenal enlargement and the secretion of ACTH and corticosterone in mice with already established tumours. Together, these results suggest that bexarotene may be developed as a potential novel therapeutic drug to better suppress Cushing's disease.
Evaluation of a test method to detect hepatitis A virus in salted shellfish
Authors: Lee Deog‐Yong , Cho Seung‐Rye , Chae Su‐Jin , Choi Wooyoung , Han Myung‐Guk
Published: January 2021

Contaminated salted shellfish were a suspected cause of the 2019 hepatitis A outbreak in Korea; however, no virus was detected in the shellfish by the virus detection tests used. In this study, we investigated the shortcomings of these detection tests for identifying hepatitis A virus in salted shellfish to serve as a guide for improvement of these tests. Salted shellfish were washed and desalted before collecting the mid‐guts for testing. For verification of the method, the mid‐guts were first inoculated with norovirus and then RT‐qPCR was performed to determine the presence of norovirus genes. The norovirus gene was amplified normally along with an internal positive control; however, when the nucleic acid was extracted to be concentrated, gene amplification was inhibited. Since NaCl was the suspected contaminant, RT‐qPCR was then performed on samples that had been desalinated for 2 days, and hepatitis A virus genes were successfully detected. Gene amplification enabled analyzing the relationship between patients in the outbreak and the distributed salted shellfish. To detect viral contamination in salted and fermented specimens such as salted shellfish, it is imperative to extract the mid‐gut intestinal tract and remove any PCR inhibitors (e.g., excess salt). In this study, desalting salted shellfish using sterile distilled water before harvesting the mid‐gut was effective in facilitating hepatitis A detection. Development of future test methods requires accurately determining the effect of PCR inhibitors through the incorporation of an IPC in genetic detection tests.
International Policies on Sharing Genomic Research Results with Relatives: Approaches to Balancing Privacy with Access
Authors: Branum Rebecca , Wolf Susan M.
Published: January 2021

Debate over return of results and incidental findings to participants in genetic and genomic research has exploded over the last decade. At this point, there is wide agreement that investigators have a responsibility to anticipate discovery of findings that may warrant return, to incorporate in protocols a plan for evaluating such findings, and to offer at least some of these results to participants consenting to such return. However, the issue of how to handle questions from a participant’s genetic relatives about their own risk, or whether investigators should alert relatives to a genetic risk they may share, has garnered much less attention. Only recently has the genomic research community begun to debate these questions and offer recommendations.
International Guidelines for Privacy in Genomic Biobanking (or the Unexpected Virtue of Pluralism)
Authors: Thorogood Adrian , Zawati Ma'n H.
Published: January 2021

In an era of unrivalled sequencing, computation and networking capability, international sharing of genomic samples and data is becoming a modus operandi for modern medical research. Researchers are collaborating to establish large collections with global scale. Having never before set foot outside the cell, the molecules that shape us are being digitized and launched across the globe. Protecting individual privacy interests in this information is a central challenge of the genomic research era.

This article reviews international privacy norms governing human genomic biobanks and databases. It will not directly consider biobanks established for other health-related purposes, such as screening or therapy. A genomic biobank is “a hybrid infrastructure,” an organized collection of human biological material combined with associated health information: physical measurements, outcome data in medical records, and epidemiological information, as well as genomic data derived from the samples.
Privacy and Biobanking in China: A Case of Policy in Transition
Authors: Chen Haidan , Chan Benny , Joly Yann
Published: January 2021

With a population of over 1.3 billion, China is the most populous country in the world. It is facing an acute aging population problem, with a projected 440 million residents over age 60 and 101 million over age 80 by 2050. Furthermore, rapid industrialization and urbanization in China have resulted in serious air pollution and associated public health problems, including an increase in respiratory diseases and cancers. These and other demographic trends have generated concerns about the cost of health care and its impact on population health. In recent years, the Chinese government has invested heavily in the fields of translational research and biobanking with the hope that research in both fields can yield effective solutions to improve the public’s health and quality of life. The establishment of national biobanks was identified as a major initiative needed for the biomedical industry in the 12th Five-Year National Development Plan of Strategic Emerging Industries promulgated by the State Council in 2012.
Biobank/Genomic Research in Nigeria: Examining Relevant Privacy and Confidentiality Frameworks
Authors: Nnamuchi Obiajulu
Published: January 2021

Health research raises profound concerns of an ethical and legal nature — concerns primarily centered on how to balance researchers’ quest for scientific discovery against societal interest in protecting individuals whose participation makes the discovery possible. Particularly in a country such as Nigeria, which, not too long ago, suffered major abuse of research subjects (Pfizer’s clinical trial of Trovafloxacin and resulting death of eleven children in 1996), deploying a robust ethicolegal regime capable of curbing excesses and protecting research participants whilst contemporaneously not frustrating scientific progress is not an easy task. This is even more critical in the context of novel scientific endeavors, such as biobanking and genomic research, particularly when a significant pool of potential donors are inadequately informed about the processes involved in their participation or the result.
Taiwan Regulation of Biobanks
Authors: Fan Chien-Te , Hung Tzu-Hsun , Yeh Chan-Kun
Published: January 2021

Taiwan is an island country situated in the northwest Pacific, close to the southeast of China. The land area is about 36,000 square kilometers. The population of Taiwan is about 23 million, and it consists of the majority Han ethnic groups (it can be further divided into Ho-ló, Hakka, and Mainlander) and dozens of minority groups who are collectively called “Formosan,” an appellation for indigenous peoples in Taiwan. Formosans can be divided into Pingpu (plain-land indigenous peoples) and Gaoshan (mountain indigenous peoples) by their living area. In recent years, marriages between Taiwanese, Mainland Chinese, and Southeast Asians have increased significantly. Because of the genetic background of the Taiwanese people, it was thought to be highly beneficial for Taiwan to establish a biobank specifically designed for the Taiwanese population, as it would enable large-scale cohort studies to be carried out for common diseases occurring in Taiwan.