bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunosuppressive Drug‐Resistant Armored T‐Cell Receptor T Cells for Immune Therapy of HCC in Liver Transplant Patients
Authors: Hafezi Morteza , Lin Meiyin , Chia Adeline , Chua Alicia , Ho Zi Zong , Fam Royce , Tan Damien , Aw Joey , Pavesi Andrea , Krishnamoorthy Thinesh Lee , Chow Wan Cheng , Chen Wenjie , Zhang Qi , Wai Lu‐En , Koh Sarene , Tan Anthony T. , Bertoletti Antonio
Published: November 2020

Background and Aims

HBV‐specific T‐cell receptor (HBV‐TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR‐T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection.

Approach and Results

We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR‐T cells in liver transplanted patients with HBV‐HCC recurrence receiving HBV‐TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF). Immunosuppressive Drug Resistant Armored TCR‐T cells of desired specificity (HBV or Epstein‐Barr virus) were then engineered by concomitantly electroporating mRNA encoding specific TCRs and mutated variants of calcineurin B (CnB) and inosine‐5′‐monophosphate dehydrogenase (IMPDH), and their function was assessed through intracellular cytokine staining and cytotoxicity assays in the presence of TAC and MMF. Liver transplanted HBV‐HCC patients receiving different immunosuppressant drugs exhibited varying levels of activated (CD39+ Ki67+) peripheral blood mononuclear cells after HBV‐TCR T‐cell infusions that positively correlate with clinical efficacy. In vitro experiments with TAC and MMF showed a potent inhibition of TCR‐T cell polyfunctionality. This inhibition can be effectively negated by the transient overexpression of mutated variants of CnB and IMPDH. Importantly, the resistance only lasted for 3‐5 days, after which sensitivity was restored.

Conclusions

We engineered TCR‐T cells of desired specificities that transiently escape the immunosuppressive effects of TAC and MMF. This finding has important clinical applications for the treatment of HBV‐HCC relapses and other pathologies occurring in organ transplanted patients.
Psychosocial Obstacles to Hepatitis C Treatment Initiation Among Patients in Care: A Hitch in the Cascade of Cure
Authors: Spradling Philip R. , Zhong Yuna , Moorman Anne C. , Rupp Loralee B. , Lu Mei , Gordon Stuart C. , Teshale Eyasu H. , Schmidt Mark A. , Daida Yihe G. , Boscarino Joseph A. ,   for the Chronic Hepatitis Cohort Study (CHeCS) Investigators
Published: November 2020

There are limited data examining the relationship between psychosocial factors and receipt of direct‐acting antiviral (DAA) treatment among patients with hepatitis C in large health care organizations in the United States. We therefore sought to determine whether such factors were associated with DAA initiation. We analyzed data from an extensive psychological, behavioral, and social survey (that incorporated several health‐related quality of life assessments) coupled with clinical data from electronic health records of patients with hepatitis C enrolled at four health care organizations during 2017‐2018. Of 2,681 patients invited, 1,051 (39.2%) responded to the survey; of 894 respondents eligible for analysis, 690 (77.2%) initiated DAAs. Mean follow‐up among respondents was 9.2 years. Compared with DAA recipients, nonrecipients had significantly poorer standardized scores for depression, anxiety, and life‐related stressors as well as poorer scores related to physical and mental function. Lower odds of DAA initiation in multivariable analysis (adjusted by age, race, sex, study site, payment provider, cirrhosis status, comorbidity status, and duration of follow‐up) included Black race (adjusted odds ratio [aOR], 0.59 vs. White race), perceived difficulty getting medical care in the preceding year (aOR, 0.48 vs. no difficulty), recent injection drug use (aOR, 0.11 vs. none), alcohol use disorder (aOR, 0.58 vs. no alcohol use disorder), severe depression (aOR, 0.42 vs. no depression), recent homelessness (aOR, 0.36 vs. no homelessness), and recent incarceration (aOR, 0.34 vs. no incarceration). Conclusion: In addition to racial differences, compared with respondents who initiated DAAs, those who did not were more likely to have several psychological, behavioral, and social impairments. Psychosocial barriers to DAA initiation among patients in care should also be addressed to reduce hepatitis C‐related morbidity and mortality.
Human Nonalcoholic Steatohepatitis on a Chip
Authors: Freag May S. , Namgung Bumseok , Reyna Fernandez Maria E. , Gherardi Ermanno , Sengupta Shiladitya , Jang Hae Lin
Published: November 2020

We developed a NASH-on-a-chip where human primary hepatocytes (HCs), Kupffer cells (KCs), and hepatic stellate cells (HSCs) were cultured in the 3D hydrogel scaffold, while a blood vessel mimetic endothelialized inlet channel was engineered using human liver sinusoidal endothelial cells (LSECs), via which the system was exposed to metabolic and inflammatory stressors. Exposing liver chips to a lipotoxic environment led to the gradual development of NASH phenotypic characteristics, including intracellular lipids accumulation, hepatocellular ballooning, HSC activation, and elevation of inflammatory and profibrotic molecular markers. We demonstrate that the NASH-on-a-chip can be used to test the efficacy of pharmacological agents to inhibit the development of NASH.

Nonalcoholic steatohepatitis (NASH), an advanced stage of nonalcoholic fatty liver disease (NAFLD), is a rapidly growing and global health problem compounded by the current absence of specific treatments. A major limiting factor in the development of new NASH therapies is the absence of models that capture the unique cellular structure of the liver microenvironment and recapitulate the complexities of NAFLD progression to NASH. Organ-on-a-chip platforms have emerged as a powerful approach to dynamically model diseases and test drugs. Herein, we describe a NASH-on-a-chip platform. Four main types of human primary liver cells (hepatocytes [HCs], Kupffer cells, liver sinusoidal endothelial cells, and hepatic stellate cells [HSCs]) were cocultured under microfluidic dynamics. Our chip-based model successfully recapitulated a functional liver cellular microenvironment with stable albumin and urea secretion for at least 2 weeks. Exposing liver chips to a lipotoxic environment led to gradual development of NASH phenotypic characteristics, including intracellular lipid accumulation, hepatocellular ballooning, HSC activation, and elevation of inflammatory and profibrotic markers. Further, exposure of the chip to elafibranor, a drug under study for the therapy of NASH, inhibited the development of NASH-specific hallmarks, causing an ˜8-fold decrease in intracellular lipids, a 3-fold reduction in number of ballooned HCs, a significant reduction in HSC activation, and a significant decrease in the levels of inflammatory and profibrotic markers compared with controls. Conclusion: We have successfully developed a microfluidic NASH-on-a-chip platform that recapitulates the main NASH histologic endpoints in a single chip and that can emerge as a powerful noninvasive, human-relevant, in vitro platform to study disease pathogenesis and develop novel anti-NASH drugs.
Knowledge of social distancing measures and adherence to restrictions during the COVID‐19 pandemic
Authors: Sturman Daniel , Auton Jaime C. , Thacker Jemma
Published: November 2020

Issue addressed

With no efficacious treatments or vaccines available, social distancing measures remain the most effective approach for reducing the transmission of the COVID‐19 virus. However, adherence to social distance measures presumably requires knowledge and understanding of the current social distancing restrictions.

Methods

A modified version of the Theory of Planned Behaviour examined the role of knowledge and understanding of current social distancing measures in predicting intentions to adhere to social distancing restrictions. An online survey was administered to respondents (N = 374) in Melbourne, Australia during a period of heightened social distancing restrictions. In addition to measuring respondents’ general intentions to adhere to restrictions, vignettes were used to assess intended behaviour in specific situations.

Results

Knowledge of social distancing restrictions predicted intentions to adhere in specific situations, but not general intentions to adhere. Knowledge of restrictions also predicted positive attitudes towards current restrictions and a greater perceived ability to adhere to the restrictions, while positive attitudes was a good predictor of both general and specific intentions to adhere.

Conclusions

The findings suggest that attitudes towards restrictions may influence whether individuals attempt to adhere to restrictions, but knowledge of the restrictions influences whether the intended behaviour actually adheres to current restrictions.

So what?

These outcomes indicate that members of the public should be educated regarding the negative consequences associated with the COVID‐19 virus and the capacity of social distancing to reduce transmission of the virus, and a need for social distancing restrictions to be uncomplicated and clearly communicated.
Data entry quality of double data entry vs automated form processing technologies: A cohort study validation of optical mark recognition and intelligent character recognition in a clinical setting
Authors: Paulsen Aksel , Harboe Knut , Dalen Ingvild
Published: November 2020

Background and Aims

Patient‐reported outcome measures (PROMs) are increasingly used in health services. Paper forms are still often used to register such data. Manual double data entry (DDE) has been defined as the gold standard for transferring data to an electronic format but is laborious and costly. Automated form processing (AFP) is an alternative, but validation in a clinical context is warranted. The study objective was to examine and validate a local hospital AFP setup.

Methods

Patients over 18 years of age who were scheduled for knee or hip replacement at Stavanger University Hospital from 2014 to 2017 who answered PROMs were included in the study and contributed PROM data. All paper PROMs were scanned using the AFP techniques of optical mark recognition (OMR) and intelligent character recognition (ICR) and were processed by DDE by health secretaries using a data entry program. OMR and ICR were used to capture different types of data. The main outcome was the proportion of correctly entered numbers, defined as the same response recorded in AFP and DDE or by consulting the original paper questionnaire at the data field, item, and PROM level.

Results

A total of 448 questionnaires from 255 patients were analyzed. There was no statistically significant difference in error proportions per 10 000 data fields between OMR and DDE for data from check boxes (3.52 95% confidence interval (CI) 2.17 to 5.72 and 4.18 (95% CI 2.68‐6.53), respectively P = .61). The error proportion for ICR (nine errors) was statistically significantly higher than that for DDE (two errors), that is, 3.53 (95% CI 1.87‐6.57) vs 0.78 (95% CI 0.22‐2.81) per 100 data fields/items/questionnaires; P = .033. OMR (0.04% errors) outperformed ICR (3.51% errors; P < .001), Fisher's exact test.

Conclusions

OMR can produce an error rate that is comparable to that of DDE. In our setup, ICR is still problematic and is highly dependent on manual validation. When AFP is used, data quality should be tested and documented.
ATF4‐modified serum exosomes derived from osteoarthritic mice inhibit osteoarthritis by inducing autophagy
Authors: Wang Yan , He Shi‐Hao , Liang Xu , Zhang Xin‐Xin , Li Shan‐Shan , Li Tian‐Fang
Published: November 2020

Activating transcription factor 4 (ATF4) is critical for chondrocyte proliferation and bone formation. Exosomes are considered as promising gene‐delivery vehicles for the treatment of osteoarthritis (OA). This study utilized the serum‐derived exosomes from OA mice as the gene‐delivery vehicles for ATF4 gene therapy and explored their therapeutic effects on OA. Meniscus injury‐induced OA model was established by the excision of anterior part of medial meniscus in the right knee of C57BL/6J mice. Exosomes were isolated from serum samples of sham and OA mice, and were referred to as sham‐Exo and OA‐Exo, respectively. ATF4‐overexpressing OA‐Exo (ATF4‐OA‐Exo) was developed by introducing ATF4 mRNA into OA‐Exo via electroporation. Four weeks after surgery, OA mice received intra‐articular injections of sham‐Exo, OA‐Exo, and ATF4‐OA‐Exo, respectively. The results showed that intra‐articular injection of ATF4‐OA‐Exo alleviated articular cartilage degeneration or damage and inflammatory response of OA mice. Autophagy was weakened in knee joint cartilage of OA mice, which was partially restored by intra‐articular injection of ATF4‐OA‐Exo. Further in vitro assays revealed that ATF4‐OA‐Exo promoted chondrocyte autophagy and inhibited chondrocyte apoptosis in the TNF‐α‐ or tunicamycin‐treated chondrocytes. Together, ATF4‐modified serum exosomes derived from OA mice protect cartilage and alleviate OA progression by inducing autophagy.
Oxidized low‐density lipoprotein accelerates the injury of endothelial cells viacirc‐USP36/miR‐98‐5p/VCAM1axis
Authors: Peng Kuang , Jiang Peiyong , Du Yafang , Zeng Dianmei , Zhao Junbi , Li Meiling , Xia Chunchen , Xie Zhong , Wu Jie
Published: November 2020

Circular RNAs (circRNAs) are a group of RNAs featured by a covalently closed continuous loop structure. This study aimed to uncover the function and mechanism of circ‐ubiquitin specific peptidase 36 (USP36) in endothelial cells treated with oxidized low‐density lipoprotein (ox‐LDL). The levels of circ‐USP36, microRNA‐98‐5p (miR‐98‐5p) and vascular cell adhesion molecule 1 (VCAM1) were examined by a quantitative real‐time polymerase chain reaction (qRT‐PCR). The viability, apoptosis and inflammation were detected by (4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, flow cytometry and enzyme‐linked immunosorbent assay (ELISA), respectively. Western blot assay was performed to detect the expression of apoptosis and proliferation‐related markers and VCAM1 protein level. The targets of circ‐USP36 and miR‐98‐5p were searched using starBase website, and dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the above predictions. Ox‐LDL exposure induced the upregulation of circ‐USP36 in HUVEC cells. Circ‐USP36 accelerated ox‐LDL‐induced apoptosis, inflammatory and viability inhibition of HUVEC cells. MiR‐98‐5p was a direct downstream gene of circ‐USP36. Circ‐USP36 promoted the injury of ox‐LDL‐induced HUVEC cells through targeting miR‐98‐5p. VCAM1 could bind to miR‐98‐5p, and the protective effects of miR‐98‐5p accumulation on ox‐LDL‐induced HUVEC cells were reversed by the transfection of VCAM1. VCAM1 was regulated by circ‐USP36/miR‐98‐5p signaling in HUVEC cells. Ox‐LDL promoted the apoptosis and inflammation but suppressed the viability of HUVEC cells through upregulating circ‐USP36, thus elevating the expression of VCAM1 via miR‐98‐5p.
Parathyroid hormone ameliorates osteogenesis of human bone marrow mesenchymal stem cells against glucolipotoxicity through p38 MAPK signaling
Authors: Wang Yuli , Huang Lintong , Qin Ziyue , Yuan Hua , Li Bing , Pan Yongchu , Wang Xiaoqian , Du Xin , Hao Shushu , Du Yifei , Wang Ruixia , Shen Yi
Published: November 2020

Diabetes mellitus (DM)‐induced glucolipotoxicity is a factor strongly contributing to alveolar bone deficiency. Parathyroid hormone (PTH) has been identified as a main systemic mediator to balance physiological calcium in bone. This study aimed to uncover PTH's potential role in ameliorating the osteogenic capacity of human bone marrow mesenchymal stem cells (HBMSCs) against glucolipotoxicity. Optimal PTH concentrations and high glucose and palmitic acid (GP) were administered to cells, followed by alkaline phosphatase (ALP) staining and ALP activity assay. Quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) and Immunoblot were carried out for assessing mRNA and protein amounts, respectively. Cell counting kit‐8 (CCK‐8) and flow cytometry were performed for quantitating cell proliferation. Osteogenesis and oxidative stress were determined, and the involvement of mitogen‐activated protein kinase (MAPK) signaling was further verified. About 1–50 mmol/ml GP significantly inhibited the osteogenic differentiation of HBMSCs. 10−9 mol/L PTH was found to be the optimal concentration for HBMSC induction. PTH had no effects on HBMSC proliferation, with or without GP treatment. PTH reversed inadequate osteogenesis and excessive oxidative stress in GP‐treated HBMSCs. Mechanistically, PTH activated p38 MAPK signaling, while inhibiting p38 MAPK‐suppressed PTH's beneficial impacts on HBMSCs. Collectively, PTH promotes osteogenic differentiation in HBMSCs against glucolipotoxicity via p38 MAPK signaling.
Facilitation Literacy: Circulating Power in Professional Learning Conversations With Teacher Colleagues
Authors: Lillge Danielle
Published: November 2020

The author describes how and why a team of literacy leaders fruitfully studied their own efforts to address the challenges they faced in supporting teacher colleagues’ learning and teaching. Actively resisting facilitation models that privilege facilitators’ power to fix colleagues’ dilemmas and consistent with their belief that professional learning is socially constructed, the facilitators adopted a view of power as a resource that, when circulated, offers people opportunities to be who they wish, and be seen as knowledgeable without challenge. To explore ways of circulating power, the facilitators studied transcripts of their interactions with colleagues. Through co‐analysis of their transcripts, the team identified five discursive strategies supporting circulation of power: identifying sticking points, listening, posing clarifying questions, reframing the challenge, and soliciting feedback. The facilitators’ efforts to circulate power cultivated generative social and discursive spaces, which afforded their colleagues opportunities to negotiate self‐identified dilemmas to advocate for themselves and their students’ literacy learning.
A Meta-Analysis of the Transferability of Bone Mineral Density Genetic Loci Associations From European to African Ancestry Populations
Authors: Yau Michelle S , Kuipers Allison L , Price Ryan , Nicolas Aude , Tajuddin Salman M , Handelman Samuel K , Arbeeva Liubov , Chesi Alessandra , Hsu Yi-Hsiang , Liu Ching-Ti , Karasik David , Zemel Babette S , Grant Struan FA , Jordan Joanne M , Jackson Rebecca D , Evans Michele K , Harris Tamara B , Zmuda Joseph M , Kiel Douglas P
Published: November 2020

Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5000 individuals with both genetic data and assessments of BMD. Genotype imputation was conducted using the 1000G reference panel. We assessed single-nucleotide polymorphism (SNP) associations with femoral neck and lumbar spine BMD in each cohort separately, then combined results in fixed effects (or random effects if study heterogeneity was high, I2 index >60) inverse variance weighted meta-analyses. In secondary analyses, we conducted locus-based analyses of rare variants using SKAT-O. Mean age ranged from 12 to 68 years. One cohort included only men and another cohort included only women; the proportion of women in the other four cohorts ranged from 52% to 63%. Of 56 BMD loci tested, one locus, 6q25 (C6orf97, p = 8.87 × 10−4), was associated with lumbar spine BMD and two loci, 7q21 (SLC25A13, p = 2.84 × 10−4) and 7q31 (WNT16, p = 2.96 × 10−5), were associated with femoral neck BMD. Effects were in the same direction as previously reported in European ancestry studies and met a Bonferroni-adjusted p value threshold, the criteria for transferability to African ancestry populations. We also found associations that met locus-specific Bonferroni-adjusted p value thresholds in 11q13 (LRP5, p < 2.23 × 10−4), 11q14 (DCDC5, p < 5.35 × 10−5), and 17p13 (SMG6, p < 6.78 × 10−5) that were not tagged by European ancestry index SNPs. Rare single-nucleotide variants in AKAP11 (p = 2.32 × 10−2), MBL2 (p = 4.09 × 10−2), MEPE (p = 3.15 × 10−2), SLC25A13 (p = 3.03 × 10−2), STARD3NL (p = 3.35 × 10−2), and TNFRSF11A (p = 3.18 × 10−3) were also associated with BMD. The majority of known BMD loci were not transferable. Larger genetic studies of BMD in African ancestry populations will be needed to overcome limitations in statistical power and to identify both other loci that are transferable across populations and novel population-specific variants. © 2020 American Society for Bone and Mineral Research (ASBMR).
Impact of Genetic and Pharmacologic Inhibition of Myostatin in a Murine Model of Osteogenesis Imperfecta
Authors: Omosule Catherine L , Gremminger Victoria L , Aguillard Ashley M , Jeong Youngjae , Harrelson Emily N , Miloscio Lawrence , Mastaitis Jason , Rafique Ashique , Kleiner Sandra , Pfeiffer Ferris M , Zhang Anqing , Schulz Laura C , Phillips Charlotte L
Published: November 2020

Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by compromised skeletal integrity, altered microarchitecture, and bone fragility. Current OI treatment strategies focus on bone antiresorptives and surgical intervention with limited effectiveness, and thus identifying alternative therapeutic options remains critical. Muscle is an important stimulus for bone formation. Myostatin, a TGF-β superfamily myokine, acts through ActRIIB to negatively regulate muscle growth. Recent studies demonstrated the potential benefit of myostatin inhibition with the soluble ActRIIB fusion protein on skeletal properties, although various OI mouse models exhibited variable skeletal responses. The genetic and clinical heterogeneity associated with OI, the lack of specificity of the ActRIIB decoy molecule for myostatin alone, and adverse events in human clinical trials further the need to clarify myostatin's therapeutic potential and role in skeletal integrity. In this study, we determined musculoskeletal outcomes of genetic myostatin deficiency and postnatal pharmacological myostatin inhibition by a monoclonal anti-myostatin antibody (Regn647) in the G610C mouse, a model of mild–moderate type I/IV human OI. In the postnatal study, 5-week-old wild-type and +/G610C male and female littermates were treated with Regn647 or a control antibody for 11 weeks or for 7 weeks followed by a 4-week treatment holiday. Inhibition of myostatin, whether genetically or pharmacologically, increased muscle mass regardless of OI genotype, although to varying degrees. Genetic myostatin deficiency increased hindlimb muscle weights by 6.9% to 34.4%, whereas pharmacological inhibition increased them by 13.5% to 29.6%. Female +/mstn +/G610C (Dbl.Het) mice tended to have similar trabecular and cortical bone parameters as Wt showing reversal of +/G610C characteristics but with minimal effect of +/mstn occurring in male mice. Pharmacologic myostatin inhibition failed to improve skeletal bone properties of male or female +/G610C mice, although skeletal microarchitectural and biomechanical improvements were observed in male wild-type mice. Four-week treatment holiday did not alter skeletal outcomes. © 2020 American Society for Bone and Mineral Research (ASBMR).
Ferritin as a key risk factor for nonalcoholic fatty liver disease in children with obesity
Authors: Zhang Junfeng , Cao Jiajia , Xu Hui , Dong Guanping , Huang Ke , Wu Wei , Ye Jingjing , Fu Junfen
Published: November 2020

Background

The association between serum ferritin and nonalcoholic fatty liver disease (NAFLD) in children with obesity is not clear. This study was designed to investigate whether serum ferritin can be an independent predictor for NAFLD.

Methods

According to the hepatic ultrasound results, a total of 347 children with obesity were enrolled in this study. Among them, 95 patients with NAFLD and 95 without NAFLD were matched for gender, age, blood pressure and body mass index, the odds ratios (OR) and 95% confidence intervals (CI) for the association of ferritin and the risk of NAFLD were analyzed.

Results

After propensity score matching, ferritin values of the patients with NAFLD were significantly higher than those without NAFLD group. Alanine aminotransferase and ferritin were strongly associated with NAFLD in multivariate stepwise logistic regression analysis. The medium and high levels of ferritin increased risk of NAFLD, and the adjusted ORs were 3.298 (95% CI:1.326‐8.204), 7.322 (95% CI:2.725‐19.574) across the ferritin concentration tertiles after adjustment for confounders. Ferritin was shown to be the best predictor for NAFLD with sensitivity and specificity of 60.0% and 77.9%, respectively, area under the curve was 0.733.

Conclusion

The results show that serum ferritin can usefully be considered as a predictor of NAFLD in children with obesity.
Current status and role of programmed ventricular stimulation in patients without sustained ventricular arrhythmias and reduced ejection fraction: Analysis of the Japan cardiac device treatment registry database
Authors: Yokoshiki Hisashi , Shimizu Akihiko , Mitsuhashi Takeshi , Ishibashi Kohei , Kabutoya Tomoyuki , Yoshiga Yasuhiro , Kohno Ritsuko , Abe Haruhiko , Nogami Akihiko ,   Members of the Implantable Cardioverter‐Defibrillator (ICD) Committee of the Japanese Heart Rhythm Society
Published: November 2020

Background

The aim of this study was to clarify the current status and role of programmed ventricular stimulation in patients without sustained ventricular arrhythmias and reduced left ventricular ejection fraction (LVEF).

Methods

The follow‐up data of the Japan cardiac device treatment registry (JCDTR) was analyzed in 746 patients with LVEF ≦35% and no prior history of sustained ventricular arrhythmias who underwent de novo implantable cardioverter‐defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT‐D) implantation between January 2011 and August 2015.

Results

Electrophysiological study (EPS) with programmed ventricular stimulation had been performed before the device implant in 118 patients (15.8%, EPS group). During the mean follow‐up of 21 ± 12 months, the rate of freedom from any death and appropriate defibrillator therapy was not significantly different between EPS group (n = 118) and No EPS group (n = 628). NYHA class II‐IV, and QRS duration were negatively associated with performing EPS. Among patients in the EPS group, the rate of ventricular tachycardia (VT)/ventricular fibrillation (VF) induction was 48%. The inducibility was not a predictor of appropriate defibrillator therapy, whereas BNP ≧535 pg/mL and no use of amiodarone were significantly associated with a risk of the appropriate therapy.

Conclusion

EPS for induction of VT/VF had been performed in about 16% of patients with reduced LVEF before primary prevention ICD/CRT‐D implantation. Elevated BNP levels and no use of amiodarone, but not inducibility of VT/VF, appeared to be associated with appropriate defibrillator therapy in these populations.
Evaluation of heart rate variability using 24‐hour Holter electrocardiography in hypertensive patients
Authors: Julario Rerdin , Mulia Eka Prasetya Budi , Rachmi Dita Aulia , A’yun Maya Qurota , Septianda Imanita , Dewi Ivana Purnama , Juwita Rahima Ratna , Dharmadjati Budi Baktijasa
Published: November 2020

Background

Hypertension (HTN) remains a serious risk factor for cardiovascular mortality across the world. Hypertensive state has been shown to be associated with autonomic nervous function. This study aimed to explore the association between autonomic nervous impairment assessed by heart rate variability (HRV) and HTN.

Methods

A total of 52 hypertensive and 55 non‐hypertensive patients were consecutively studied using 24‐hour Holter. The hypertensive patients were grouped into controlled blood pressure (BP) and uncontrolled BP. This study compared HRV in non‐hypertensive and hypertensive patients; and hypertensive patients with controlled and uncontrolled BP. HRV parameters include time and frequency domain.

Results

Mean age for hypertensive and non‐hypertensive patients were 53.58 ± 14.31 and 44.89 ± 16.63 years old, respectively. Median (IQR) SDNN for hypertensive and non‐hypertensive group were 109.00 (90.00‐145.00) and 129.00 (107.00‐169.00), respectively. SDNN, ASDNN, rMSSD, pNN50, BB50, VLF, and HF values were significantly lower in the hypertensive group compared to non‐hypertensive group (all P < .05). A multiple regression analysis showed that HRV parameters: SDANN, ASDNN, rMSSD, and LF values were independent risk factors of HTN. SDNN, SDANN, ASDNN, VLF, LF, and HF values were significantly lower in the uncontrolled BP compared to controlled BP group (all P < .05). A multiple regression analysis showed that HRV parameters: SDNN, SDANN, rMSSD, and HF values were independent risk factors of uncontrolled BP in hypertensive patients.

Conclusions

Our study showed that cardiac autonomic nervous impairment, as demonstrated by reduced HRV, is significantly associated with HTN. Decreased HRV was more evident in uncontrolled BP than in controlled BP group.
Amplification of Winter Sea surface temperature response over East China Seas to global warming acceleration and slowdown
Authors: Tan Hongjian , Cai Rongshuo , Yan Xiuhua , Li Cuihua
Published: November 2020

The global mean surface temperature does not increase monotonously over the past decades, with accelerated warming from the late 1970s to 1998 and followed by the warming slowdown during 1998–2013 (the so‐called warming hiatus). This study assessed and compared the temporal evolutions of sea surface temperature (SST) trends in the East China Seas (ECS, including Bohai, Yellow and East China Sea) and other key ocean regions. The results revealed an amplified response of ECS SST to both global warming acceleration and hiatus. This amplification was manifested as remarkably enhanced winter warming rates in the ECS of over 1.1 and 0.8°C⋅decade–1 for the 1980–1989 and 1990–1999, respectively, and as an obvious cooling trend of nearly −0.5°C⋅decade‑1 during 1998–2013. The enhanced response can be explained well by the combined effects of the Kuroshio Current (KC) and East Asian Winter Monsoon (EAWM). The weakened EAWM during the 1980s, accompanied by lower wind speeds and higher air temperatures, impeded the releases of latent and sensible heat fluxes from the ocean to the atmosphere, resulting in rapid ECS warming. During 1998–2013, the strengthened EAWM led to the enhanced cooling trend in the ECS. In addition, the volume transport of the KC east of Taiwan strengthened (weakened) during the 1990s (2000s), which might also have contributed to the enhanced warming (cooling) in the ECS. Our research suggests their sensitivity makes the ECS potentially vulnerable to the effects of global climate change, which has important implications regarding regional impact assessments.
Sweetness Perception is not Involved in the Regulation of Blood Glucose after Oral Application of Sucrose and Glucose Solutions in Healthy Male Subjects
Authors: Grüneis Verena , Schweiger Kerstin , Galassi Claudia , Karl Corinna M. , Treml Julia , Ley Jakob P. , König Jürgen , Krammer Gerhard E. , Somoza Veronika , Lieder Barbara
Published: November 2020

Scope

This study investigates the effect of the sweetness of a sucrose versus an isocaloric glucose solution in dietary concentrations on blood glucose regulation by adjusting the sweetness level using the sweet taste inhibitor lactisole.

Methods and Results

A total of 27 healthy males participated in this randomized, crossover study with four treatments: 10% glucose, 10% sucrose, 10% sucrose + 60 ppm lactisole, and 10% glucose + 60 ppm lactisole. Plasma glucose, insulin, glucagon‐like peptide 1, and glucagon levels are measured at baseline and 15, 30, 60, 90, and 120 min after beverage consumption. Test subjects rated the sucrose solution to be sweeter than the isocaloric glucose solution, whereas no difference in sweetness is reported after addition of lactisole to the sucrose solution. Administration of the less sweet glucose solution versus sucrose led to higher blood glucose levels after 30 min, as reflected by a lower ΔAUC for sucrose (1072 ± 136) than for glucose (1567 ± 231). Application of lactisole leads to no differences in glucose, insulin, or glucagon responses induced by sucrose or glucose.

Conclusion

The results indicate that the structure of the carbohydrate has a stronger impact on the regulation of blood glucose levels than the perceived sweetness.
Overexpression of exogenous biuret hydrolase in rice plants confers tolerance to biuret toxicity
Authors: Ochiai Kumiko , Uesugi Asuka , Masuda Yuki , Nishii Megumi , Matoh Toru
Published: November 2020

Biuret, a common impurity in urea fertilizers, is toxic to plants, but little is known about the physiological mechanisms underlying its toxicity. Here, we analyzed biuret toxicity in rice (Oryza sativa) plants. We carried out uptake experiments using 15N‐labelled biuret and demonstrated that biuret could reach sub millimolar concentrations in rice plants. We also demonstrated that the hydrolysis of biuret in plant cells could confer biuret tolerance to rice plants. This occurred because transgenic rice plants that overexpressed an exogenous biuret hydrolase cloned from a soil bacterium gained improved tolerance to biuret toxicity. Our results indicate that biuret toxicity is not an indirect toxicity caused by the presence of biuret outside the roots, and that biuret is not quickly metabolized in wild‐type rice plants. Additionally, it was suggested that biuret was used as an additional nitrogen source in transgenic rice plants, because biuret hydrolase‐overexpressing rice plants accumulated more biuret‐derived N, as compared to wild‐type rice.
Potassium nutrition in oil palm: The potential of metabolomics as a tool for precision agriculture
Authors: Cui Jing , Chao de la Barca Juan Manuel , Lamade Emmanuelle , Tcherkez Guillaume
Published: November 2020

Societal Impact Statement

Oil palm is the first oil‐producing crop globally, representing nearly 20 million ha. In the recent past, oil palm cultivation has been controversial not only because of land utilisation at the expense of primary tropical forests or health concerns associated with palm oil, but also pollution caused by fertilization (including CO2 produced to synthesise fertilizers). Oil palm fields are heavily fertilized with potassium (K), and thus finding better, more parsimonious methods to monitor K nutrition is more important than ever. Here, we suggest that metabolomics and subsequent machine learning of metabolic signatures represent a promising tool to probe K requirements, opening avenues for precision agriculture in oil palm industry.
Genome‐wide assessment and development of molecular diagnostic methods for imidacloprid‐resistance in the brown planthopper, Nilaparvata lugens (Hemiptera; Delphacidae)
Authors: Yokoi Kakeru , Nakamura Yuki , Jouraku Akiya , Akiduki Gaku , Uchibori‐Asano Miwa , Kuwazaki Seigo , Suetsugu Yoshitaka , Daimon Takaaki , Yamamoto Kimiko , Noda Hiroaki , Sanada‐Morimura Sachiyo , Matsumura Masaya , Cuong Le Quoc , Van Chien Ho , Estoy Gerardo F , Shinoda Tetsuro
Published: November 2020

BACKGROUND

The brown planthopper, Nilaparvata lugens (Stål), is one of the most notorious pests of rice throughout Asia. The brown planthopper has developed high resistance to imidacloprid, a member of neonicotinoid insecticides. Several genes and mutations conferring imidacloprid resistance in N. lugens, especially in eastern and southeastern Asia populations, have been reported. Thus, the key mechanisms of imidacloprid resistance need to be examined.

RESULTS

RNA‐seq analyses revealed that only one cytochrome P450 monooxygenase gene, CYP6ER1, was commonly upregulated in the five resistant strains tested. Sequences of CYP6ER1, which were highly expressed in the imidacloprid‐resistant strains, contained a three‐nucleotide deletion in the coding region, and amino acid substitutions and deletion, compared to that in an imidacloprid‐susceptible strain. RNAi‐mediated gene knockdown of CYP6ER1 increased imidacloprid susceptibility in a resistant strain. Further, we established two simple and convenient PCR‐based molecular diagnostic methods to detect the CYP6ER1 locus with the three‐nucleotide deletion. Using these methods, the resistance of F2 progenies derived from the crosses of F1 siblings from susceptible and resistant parents was analyzed, showing that the imidacloprid resistance had a relationship to the CYP6ER1 locus with the three‐nucleotide deletion.

CONCLUSION

The overexpression of a variant CYP6ER1 with amino acid substitutions and deletion was involved in imidacloprid resistance in N. lugens. Based on these findings, molecular diagnostic methods have been developed and are promising tools for monitoring imidacloprid resistance in paddy fields. © 2020 Society of Chemical Industry
Steered Quantum Coherence and Quantum Criticality in the XY Model with Dzyaloshinsky–Moriya Interaction
Authors: Xie Yu-Xia
Published: November 2020

The critical behaviors of the steered quantum coherence (SQC) in the transverse field XY model with Dzyaloshinsky–Moriya (DM) interaction are explored. It is found that there is an inflexion for the SQC at the critical field of quantum phase transition (QPT) for two long‐distance spins, and there is a divergence for the derivative of the SQC with respect to the magnetic field at the critical field of QPT for any two spins in the chain. Moreover, SQC shows distinct behaviors in different phase regions of the model, which is also a signature of the QPT. Furthermore, the SQC method is robust in studying quantum criticality even under environmental coupling.
“Rapunzel, Rapunzel,Lanza Tu Pelo”: Storytelling in a Transcultural, Translanguaging Dialogic Exchange
Authors: Flynn Erin E.
Published: November 2020

In this study, we examined story circles to understand how the small‐group activity supports and shapes the storytelling of young students in multicultural, multilingual preschool classrooms. Through a representative example, we show how language development unfolds in the context of a transcultural and translanguaging dialogic exchange of stories. We describe features of increasing linguistic complexity present in students’ storytelling as they established affinity‐affirming connections over ideas, shared ways of languaging, and shared ways of storytelling. By examining changes in one student’s storytelling in the context of a mixed‐language story circle group, we offer insights into both language development and features of the language ecology in which such changes are supported.
The damselfly palaeofauna from the Eocene of Wyoming and Colorado, USA (Insecta, Odonata, Zygoptera)
Authors: Bechly Günter , Garrouste Romain , Aase Arvid , Karr Jered A. , Grande Lance , Nel André
Published: November 2020

A new family, five new genera, and nine new species of fossil damselflies (Insecta, Odonata, Zygoptera, Calopterygida) from the USA are described, seven from the Eocene Fossil Lake deposits and one from Lake Uinta deposits, both from the Green River Formation, and an additional specimen from the Wind River Formation of Wyoming and Colorado. Namely, Carlea eocenica gen. et sp. nov. (in Carleidae fam. nov.), Labandeiraia riveri sp. nov., Labandeiraia browni sp. nov., Eodysphaea magnifica gen. et sp. nov., Litheuphaea sp. cf. coloradensis Petrulevičius et al., 2007, Zacallites cockerelli sp. nov., Dysagrion integrum sp. nov., Tenebragrion shermani gen. et sp. nov., Tynskysagrion brookeae gen. et sp. nov., and Oreodysagrion tenebris gen. et sp. nov. Epallagoidea and Amphipterygoidea are most common while Calopterygoidea, Coenagrionoidae and Lestoidea damselflies are less diverse. Genera of zygopteran Dysagrionidae are known from Europe and North America, further supporting the hypothesis of Palaeogene terrestrial interchange. Representatives of Epallagoidea and Amphipterygoidea in the Green River Formation confirm that warm conditions occurred at the time of deposition.
Four millennia of vegetation and environmental history above the Hyrcanian forest, northern Iran
Authors: Homami Totmaj Leila , Ramezani Elias , Alizadeh Kammaledin , Behling Hermann
Published: November 2020

Past vegetation, fire, and climate dynamics, as well as human impact, have been reconstructed for the first time in the highlands of the Gilan province in the Alborz mountains (above the Hyrcanian forest) for the last 4,300 cal yrs bp. Multi-proxy analysis, including pollen, spores, non-pollen palynomorphs, charcoal, and geochemical analysis, has been applied to investigate the environmental changes at 2,280 m a.s.l., above the Hyrcanian forest. Dominant steppe vegetation occurred in the study area throughout the recorded period. The formation of the studied mire deposits, as well as vegetation composition, suggest a change to wetter climatic conditions after 4,300 until 1,700 cal yrs bp. Fires were frequent, which may imply long-lasting anthropogenic activities in the area. Less vegetation cover with a marked decrease of the Moisture Index (MI) suggests drier conditions between 1,700 and 1,000 cal yrs bp. A high proportion of Cichorioideae and Amaranthaceae, as well as the reduction of trees, in particular Fagus and Quercus, at lower elevations, indicate human activities such as intense livestock grazing and deforestation. Soil erosion as the result of less vegetation due to dry conditions and/or human activities can be reconstructed from a marked increase of Glomus spores and high values of K and Ti. Since 1,000 cal yrs bp, the increasing MI, as well as the rise of Poaceae and Cyperaceae together with forest recovery, suggest a change to wetter conditions. The occurrence of still frequent Cichorioideae and Plantago lanceolata along with Sordaria reflect continued intense grazing of livestock by humans.
Radio-luno-triquetral bone-ligament transfer as an additional stabilizer in scapholunate-instability
Authors: Haug Luzian C. P. , Adler Tom , Bignion Dietmar , Voegelin Esther
Published: November 2020

Introduction

Reconstruction of the scapho-lunate (SL) ligament is still challenging. Many different techniques, such as capsulodesis, tendon graft and bone-ligament-bone graft have been described to stabilize reducible SL dissociation. If primary ligament repair alone is not possible, an additional stabilizer is needed to achieve scapho-lunate stability. A new local bone-ligament transfer using half of the radio-luno-triquetral ligament is performed. The direction of traction of the transposed ligament is very similar to the original ligament. Ideal tension can be attained by fixation of the bone block at the dorsal ridge of the scaphoid. The biomechanical stability of this bone-ligament transfer shall be examined biomechanically.

Material and methods

Computed tomography imaging was performed using eight cadaveric forearms with a defined position of the wrist. Axial load was accomplished with tension springs attached to the extensor and flexor tendons. Three series ([a] native, [b] divided SL ligament and [c]) after reconstruction with bone-ligament transfer] were reconstructed three-dimensionally to determine the angles between radius, scaphoid and lunate. The radial distal part including a bone fragment of the radio-luno-triquetral ligament was transferred from its insertion at the distal edge of the radius to be attached to the dorsal ridge of the scaphoid.

Results

SL gap was widened after its transection. Average SL distance was 6.6 ± 1.6 mm. After ligament reconstruction, the gap could be narrowed significantly to 4.2 mm (± 0.7 mm). The movement of the scaphoid and lunate showed significant changes, especially in wrist flexion, fist closure and radial deviation. These deviations could be corrected by the bone ligament transfer.

Conclusion

Reconstruction of a transected SL ligament with a bone-ligament transfer from the radio-luno-triquetral ligament reduces SL dissociation under axial load. The described surgical technique causes low donor-side morbidity and can be considered in addition to improve stability if SL ligament suture alone does not appear sufficient.

Level of evidence

Level II, therapeutic investigating experimental study.
Who is Best at Mediating a Social Conflict? Comparing Robots, Screens and Humans
Authors: Druckman Daniel , Adrian Lin , Damholdt Malene Flensborg , Filzmoser Michael , Koszegi Sabine T. , Seibt Johanna , Vestergaard Christina
Published: November 2020

The impacts of various mediation platforms on negotiation outcomes and perceptions are compared in this article. The mediator platforms contrasted were a (teleoperated) Telenoid robot, a human, and a computer screen. All of these platforms used the same script for process diagnosis, analysis, and advice on how to resolve an impasse in a simulated high-tech company de-merger negotiation. A fourth experimental condition consisted of a no-mediation control. More agreements and more integrative agreements were attained by the robotic platform than by the other types of mediator platforms and the control. Mediation via the Telenoid robot also produced more non-structured agreements, which consisted of decisions made outside of the scenario options. Negotiators in this condition had more positive perceptions of the mediation experience, were more satisfied with the outcome, and thought that the mediator’s advice was more useful. Indirect analyses showed that the outcomes mediated the effects of the conditions on perceived satisfaction. Implications of the findings are discussed in terms of responses to novelty, which include creative and divergent modes of thinking.
Kelp in IMTAs: small variations in inorganic nitrogen concentrations drive different physiological responses of Saccharina latissima
Authors: Rugiu L. , Hargrave M. S. , Enge S. , Sterner M. , Nylund G. M. , Pavia H.
Published: November 2020

Kelps can be included in integrated multitrophic aquaculture (IMTA) where their growth and quality might benefit from the nutrient load released by other species like finfish and mussels transforming effluents from the cultured animals into valuable products. We studied how different nutrient concentrations affect growth, photosynthesis, chemical composition and pigment content of the kelpSaccharina latissima. We exposed kelps to natural seawater, water enriched to levels of ammonium and nitrate simulating finfish cage waste (IMTA1) and a combination of such enrichment with natural effluents coming from mussels (IMTA2). The algal biomass was higher and produced elevated total organic content when exposed to both IMTA1 and IMTA2. The photosynthetic responses in terms of relative electron transfer rate (rETRmax), PSII saturation irradiance (Ek) and total nitrogen content were also positively affected by both IMTA1 and IMTA2. We found a significant enhancement in pigment content only when algae were exposed to the strongest enrichment of our study (IMTA2). Finally, we found a positive relationship between rETRmaxand growth, and the content of chlorophyllaand fucoxanthin. Our results show significant physiological responses ofS. latissimato nutrient enrichment mimicking IMTA settings, as well as the benefit of added nutrients through a boost in photosynthetic activity that leads to higher kelp biomass and pigment production. This study suggests that modest nitrogen enrichment such as the one in our IMTA2 setup is enough to generate not only higher kelp biomass, but also an increased biomass quality with potentially higher market value.