bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic comparison of three fully automated chemiluminescent immunoassay platforms for the detection of SARS-CoV-2 antibodies
Authors: Parai Debaprasad , Dash Girish Chandra , Choudhary Hari Ram , Peter Annalisha , Rout Usha Kiran , Nanda Rashmi Ranjan , Kshatri Jaya Singh , Kanungo Srikanta , Palo Subrata Kumar , Turuk Jyotirmayee , Pati Sanghamitra , Bhattacharya Debdutta
Published: October 2020

The whole world is battling against coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various strategies are taken to curb the spread of the virus and to move out from the enforced lockdown stage. Serological tests are the neediest diagnostic and surveillance tool to complement the gold standard molecular diagnostic method to track down the transmission rate of SARS-CoV-2. Automated chemiluminescent immunoassay (CLIA) based analyzers become highly demanding platforms both to clinicians and policy makers for the detection anti-SARS-CoV-2 antibodies. In this study, serum from 594 patients positive for COVID-19 and 100 samples from pre-COVID cases were tested by three automated platforms: Abbott architect i2000SR, Roche cobas e411 and Yhlo iFlash 1800 and their diagnostic accuracy were compared. All three platforms showed high specificity as claimed by manufacturer. Clinical sensitivities of the machines were calculated as 64.48% (58.67-70.3) for Abbott, 80.48% (76.62-84.34) for Roche and 76.94% (72.65-81.23) for Yhlo. The Cohen’s kappa value was determined from 0.69-0.89 when inter-rater agreements were calculated. The area under the curves (AUC) values demonstrated Roche Cobas e411 as the diagnostically most accurate platform among the three CLIA analyzers.
How deep brain stimulation and levodopa affect gait variability in Parkinson’s disease
Authors: Su Zi , Patel Salil , Gavin Bronwyn , Buchanan Tim , Bogdanovic Marko , Sarangmat Nagaraja , Green Alexander L. , Aziz Tipu Z. , FitzGerald James J. , Antoniades Chrystalina A.
Published: October 2020

Background

Disorders of gait are a very common feature of Parkinson’s Disease. We examined how deep brain stimulation of the subthalamic nucleus (STN DBS) and dopaminergic medication affect gait and more specifically its rhythmicity.

Objectives

We accurately quantified multiple gait parameters in Parkinson’s patients during on and off stages of their treatment (levodopa or STN DBS) to compare and contrast the treatment-induced changes in gait.

Methods

We studied 11 patients with STN DBS, 15 patients on levodopa and 42 healthy controls. They all completed the MDS-UPDRS part III along with a gait assessment protocol while wearing six nine-axis inertial measurement units (lumbar, sternal, and all four extremities).

Results

Both medication and stimulation significantly improved stride length, while medication further significantly increased gait speed. In the lower limbs, both medication and stimulation had a normalising effect on lower limb angles, significantly increasing the foot strike angle and toe-off angle.

Conclusions

STN DBS reduced the step to step variability in a range of lower limb gait parameters in PD, while antiparkinsonian medication had no significant effect. This suggests that STN stimulation, but not dopaminergic medication, has access to circuits that control gait rhythm, and that the resulting effect of stimulation on gait is beneficial. However, the results we observed for movement of the trunk and upper limbs were strikingly different to those seen in the lower limbs. We propose a hypothesis to explain why we observe these results, focusing on cholinergic pedunculopontine projections.
Isolation of infected people and their contacts is likely to be effective against many short-term epidemics
Authors: Geffen Nathan , Low Marcus
Published: October 2020

Background

Isolation of infected people and their contacts may be an effective way to control outbreaks of infectious disease, such as influenza and SARS-CoV-2. Models can provide insights into the efficacy of contact tracing, coupled with isolating or quarantining at risk people.

Methods

We developed an agent-based model and simulated 15, 000 short term illnesses, with varying characteristics. For each illness we ran ten simulations on the following scenarios: (1) No tracing or isolation (None), (2) isolation of agents who have tested positive (Isolation), (3) scenario 2 coupled with minimal contact tracing and quarantine of contacts (Minimum), (4) scenario 3 with more effective contact tracing (Moderate), and (5) perfect isolation of agents who test positive and perfect tracing and quarantine of all their contacts (Maximum).

Results

The median total infections of the Isolation, Minimum, Moderate and Maximum scenarios were 80%, 40%, 17% and 4% of the no intervention scenario respectively.

Conclusions

Isolation of infected patients and quarantine of their contacts, even if moderately well implemented, is likely to substantially reduce the number of infections in an outbreak. Randomized controlled trials to confirm these results in the real world and to analyse the cost effectiveness of contact tracing and isolation during coronavirus and influenza outbreaks are warranted.
Probabilistic method corrects previously uncharacterized Hi-C artifact
Authors: Shen Yihang , Kingsford Carl
Published: October 2020

Three-dimensional chromosomal structure plays an important role in gene regulation. Chromosome conformation capture techniques, especially the high-throughput, sequencing-based technique Hi-C, provide new insights on spatial architectures of chromosomes. However, Hi-C data contains artifacts and systemic biases that substantially influence subsequent analysis. Computational models have been developed to address these biases explicitly, however, it is difficult to enumerate and eliminate all the biases in models. Other models are designed to correct biases implicitly, but they will also be invalid in some situations such as copy number variations. We characterize a new kind of artifact in Hi-C data. We find that this artifact is caused by incorrect alignment of Hi-C reads against approximate repeat regions and can lead to erroneous chromatin contact signals. The artifact cannot be corrected by current Hi-C correction methods. We design a probabilistic method and develop a new Hi-C processing pipeline by integrating our probabilistic method with the HiC-Pro pipeline. We find that the new pipeline can remove this new artifact effectively, while preserving important features of the original Hi-C matrices.
Mechanisms underlying vaccination protocols that may optimally elicit broadly neutralizing antibodies against highly mutable pathogens
Authors: Ganti Raman S. , Chakraborty Arup K.
Published: October 2020

Effective prophylactic vaccines usually induce the immune system to generate potent antibodies that can bind to an antigen and thus prevent it from infecting host cells. B cells produce antibodies by a Darwinian evolutionary process called affinity maturation (AM). During AM, the B cell population evolves in response to the antigen to produce antibodies that bind specifically and strongly to the antigen. Highly mutable pathogens pose a major challenge to the development of effective vaccines because antibodies that are effective against one strain of the virus may not protect against a mutant strain. Antibodies that can protect against diverse strains of a mutable pathogen have high “breadth” and are called broadly neutralizing antibodies (bnAbs). In spite of extensive studies, an effective vaccination strategy that can generate bnAbs in humans does not exist for any highly mutable pathogen. Here we study a minimal model to explore the mechanisms underlying how the selection forces imposed by antigens can be optimally chosen to guide AM to maximize the evolution of bnAbs. For logistical reasons, only a finite number of antigens can be administered in a finite number of vaccinations; that is, guiding the non-equilibrium dynamics of AM to produce bnAbs must be accomplished non-adiabatically. The time-varying Kullback-Leibler divergence (KLD) between the existing B cell population distribution and the fitness landscape imposed by antigens is a quantitative metric of the thermodynamic force acting on B cells. If this force is too small, adaptation is minimal. If the force is too large, contrary to expectations, adaptation is not faster; rather, the B cell population is extinguished for reasons that we describe. We define the conditions necessary for the force to be set optimally such that the flux of B cells from low to high breadth states is maximized. Even in this case we show why the dynamics of AM prevent perfect adaptation. If two shots of vaccination are allowed, the optimal protocol is characterized by a relatively low optimal KLD during the first shot that appropriately increases the diversity of the B cell population so that the surviving B cells have a high chance of evolving into bnAbs upon subsequently increasing the KLD during the second shot. Phylogenetic tree analysis further reveals the evolutionary pathways that lead to bnAbs. The connections between the mechanisms revealed by our analyses and recent simulation studies of bnAb evolution, the problem of generalist versus specialist evolution, and learning theory are discussed.
Pseudomonas aeruginosaStimulates Inflammation and Enhances KSHV-Induced Cell Proliferation and Cellular Transformation through Both LPS and Flagellin
Authors: Markazi Ashley , Bracci Paige M. , McGrath Michael , Gao Shou-Jiang
Published: October 2020

Inflammation triggered by innate immunity promotes carcinogenesis in cancer. Kaposi’s sarcoma (KS), a hyperproliferative and inflammatory tumor caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, is the most common cancer in AIDS patients. KSHV infection sensitizes cells to pathogen-associated molecular patterns (PAMPs). We examined the role ofPseudomonas aeruginosa(PA), an opportunistic bacterium that can affect AIDS patients, in inflammation and cell proliferation of KSHV-transformed cells. PA stimulation increased cell proliferation and efficiency of colony formation in softagar of KSHV-transformed rat primary mesenchymal precursor (KMM) cells but had no significant effect on the untransformed (MM) cells. PA stimulation also increased cell proliferation of KSHV-infected human B-cells, Bjab, but not the uninfected cells. Mechanistically, PA stimulation resulted in increased inflammatory cytokines and activation of p38, ERK1/2, and JNK mitogen-activated protein kinase (MAPK) pathways in KMM cells while having no obvious effect on MM cells. PA induction of inflammation and MAPKs were observed with and without inhibition of Toll-like receptor 4 (TLR4) pathway while a flagellin-deleted mutant of PA required a functional TLR4 pathway to induce inflammation and MAPKs. Furthermore, treatment with both LPS or flagellin alone was sufficient to induce inflammatory cytokines, activate MAPKs, and increase cell proliferation and efficiency of colony formation in softagar of KMM cells. These results demonstrate that both LPS and flagellin are PAMPs that contribute to PA induction of inflammation in KSHV-transformed cells. Because AIDS-KS patients are susceptible to PA infection, our work highlights the preventive and therapeutic potential of targeting PA infection in these patients.

Importance

Kaposi’s sarcoma (KS), caused by infection of Kaposi’s sarcoma-associated herpesvirus (KSHV), is one of the most common cancers in AIDS patients. KS is a highly inflammatory tumor but how KSHV infection induces inflammation remains unclear. We have previously shown that KSHV infection upregulates Toll-like receptor 4 (TLR4), sensitizing cells to lipopolysaccharide (LPS) andEscherichia coli. In the current study, we examined the role ofPseudomonas aeruginosa(PA), an opportunistic bacterium that can affect AIDS patients, in inflammation and cell proliferation of KSHV-transformed cells. PA stimulation increased cell proliferation, inflammatory cytokines, and activation of growth and survival pathways in KSHV-transformed cells through two pathogen-associated molecular patterns LPS and flagellin. Because AIDS-KS patients are susceptible to PA infection, our work highlights the preventive and therapeutic potential of targeting PA infection in these patients.
Hybrid assembly of an agricultural slurry virome reveals a diverse and stable community with the potential to alter the metabolism and virulence of veterinary pathogens
Authors: Cook Ryan , Hooton Steve , Trivedi Urmi , King Liz , Dodd Christine E.R. , Hobman Jon L. , Stekel Dov J. , Jones Michael A. , Millard Andrew D.
Published: October 2020

Background

Viruses are the most abundant biological entities on Earth, known to be crucial components of microbial ecosystems. However, there is little information on the viral community within agricultural waste. There are currently~2.7 million dairy cattle in the UK producing 7-8% of their own bodyweight in manure daily, and 28 million tonnes annually. To avoid pollution of UK freshwaters, manure must be stored and spread in accordance with guidelines set by DEFRA. Manures are used as fertiliser, and widely spread over crop fields, yet little is known about their microbial composition. We analysed the virome of agricultural slurry over a five-month period using short and long-read sequencing.

Results

Hybrid sequencing uncovered more high-quality viral genomes than long or short-reads alone; yielding 7,682 vOTUs, 174 of which were complete viral genomes. The slurry virome was highly diverse and dominated by lytic bacteriophage, the majority of which represent novel genera (~98%). Despite constant influx and efflux of slurry, the composition and diversity of the slurry virome was extremely stable over time, with 55% of vOTUs detected in all samples over a five-month period. Functional annotation revealed a diverse and abundant range of auxiliary metabolic genes and novel features present in the community. Including the agriculturally relevant virulence factor VapE, which was widely distributed across different phage genera that were predicted to infect several hosts. Furthermore, we identified an abundance of phage-encoded diversity-generating retroelements, which were previously thought to be rare on lytic viral genomes. Additionally, we identified a group of crAssphages, including lineages that were previously thought only to be found in the human gut.

Conclusions

The cattle slurry virome is complex, diverse and dominated by novel genera, many of which are not recovered using long or short-reads alone. Phages were found to encode a wide range of AMGs that are not constrained to particular groups or predicted hosts, including virulence determinants and putative ARGs. The application of agricultural slurry to land may therefore be a driver of bacterial virulence and antimicrobial resistance in the environment.
Persistence of Zika virus RNA in the epididymis of the male reproductive tract
Authors: Vogt Megan B. , Frere Francesca , Hawks Seth A. , Perez Claudia E. , Coutermarsh-Ott Sheryl , Duggal Nisha K.
Published: October 2020

Zika virus (ZIKV) can infect developing fetusesin uteroand cause severe congenital defects. Thisin uterotransmission can occurs following ZIKV infection during pregnancy via sexual transmission or mosquito bite. Infected men may shed ZIKV RNA in semen for over six months post symptom onset, indicating that ZIKV may persistently infect the male reproductive tract (MRT). However, the site of persistent infection in the MRT and whether ZIKV can recrudesce in the MRT is unknown. We hypothesized that if ZIKV establishes a persistent infection in the MRT, then immunosuppressant treatment should stimulate ZIKV replication. We tested this hypothesis in a wild-type mouse model of ZIKV sexual transmission. Male mice were infected with ZIKV and immunosuppressed when they no longer shed infectious virus in their ejaculates. After immunosuppression, ejaculates and MRT tissues were monitored for infectious virus and ZIKV RNA. Our results show that ZIKV recrudescence did not occur following immunosuppression, as we did not detect significant levels of infectious virus in ejaculates or MRT tissues following immunosuppression. We did detect ZIKV RNA in the epididymides of mice treated with the immunosuppressant cyclophosphamide. Further analysis revealed that this ZIKV RNA was contained within the lumen of the epididymis. Our findings suggest that ZIKV persistently infects the epididymis within the male reproductive tract. This study provides insight into the mechanisms behind ZIKV sexual transmission, which may inform public health decisions regarding ZIKV risks.

Importance

Zika virus (ZIKV) is an emerging mosquito-transmitted virus that typically causes mild and self-limiting febrile illness in humans; however, during the recent epidemic of ZIKV in the Americas, severe birth defects, such as microcephaly and club foot, were reported in infants born to ZIKV infected mothers. Additionally, sexual transmission has been identified as a secondary method of ZIKV transmission. Since ZIKV can be isolated from semen of infected men long after initial infection, it is imperative to understand the mechanism(s) of ZIKV infection of the male reproductive tract to prevent sexual transmission and ZIKV-associated birth defects. The significance of our research is in identifying a site of persistent ZIKV infection in the male reproductive tract and in assessing the likelihood that a persistently infected individual will begin shedding infectious virus in semen again. This information will enhance our understanding of ZIKV sexual transmission and inform health decisions regarding ZIKV risks.
Function expansion of antitumor transcriptional activator NFE2L1 by the original discovery of its non-transcription factor activity
Authors: Lu Qiu , Qiufang Yang , Peng Li , Xiaowen Zhou , Yonghui Yang , Xiuman Zhou , Shanshan Gou , Wenjie Zhai , Guodong Li , Yonggang Ren , Wenshan Zhao , Yahong Wu , Yuanming Qi , Yanfeng Gao
Published: October 2020

Antitumor transcription activator NFE2L1, with the functions to regulate redox homeostasis, protein turnover, and material metabolism, plays an important role in embryonic development and specialization of tissue and organ functions. Deficiency ofNFE2L1gene in different regions yields distinct phenotypes, suggesting that NFE2L1 may have a transcription factor-independent function. Here we originally discovered the non-transcription factor activity of NFE2L1 by constructing a truncated protein-NFE2L1ΔCwithout 152 aa at the C-terminus which lost the transcription factor activity. The regulation of NFE2L1 on redox homeostasis, proteasome function, and immune response mainly depends on its transcription activator function in nucleus, while the regulation on metabolism, ribosome function, and canceration is germanely to its non-transcription factor activity in cytoplasm. Surprisingly, the results indicated the tumor suppressive effect of NFE2L1 by repression of Wnt/β-catenin signaling in a non-transcription factor manner, indicating the potential value of NFE2L1 as a therapeutic target in clinical cancer treatment independent of its transcription factor activity. Our observations reveal the non-transcription factor activity of NFE2L1 for the first time, and lay foundation for the basic and applied research of NFE2L1.
Modulation of Transient receptor potential melastatin 3 by protons through its intracellular binding sites
Authors: Saad Md Zubayer Hossain , Xiang Liuruimin , Liao Yan-Shin , Reznikov Leah R. , Du Jianyang
Published: October 2020

Transient receptor potential melastatin 3 channel (TRPM3) is a calcium-permeable nonselective cation channel that plays an important role in modulating glucose homeostasis in the pancreatic beta cells. However, how TRPM3 is regulated under physiological and pathological conditions is poorly understood. In this study, we found that both intracellular and extracellular protons block TRPM3 through its intracellular binding sites. We demonstrated that external protons indirectly block TRPM3, whereas internal protons inhibit TRPM3 directly with an inhibitory pH50of 6.9 ± 0.11. We identified three titratable residues, D1059, D1062, and D1073, at the inner vestibule of the channel pore that contribute to pH sensitivity. The mutation of D1073Q reduces TRPM3 current intensity and pH sensitivity; Replacement of Asp 1073 by Gln 1073 changes the reduction of TRPM3 outward current by low external pH 5.5, from 62 ± 3 % in WT to 25 ± 6.0 % in D1073Q. These results indicate that D1073 is not only essential for intracellular pH sensitivity, but it is also crucial for TRPM3 channel gating. In addition, a single mutation of D1059 or D1062 enhances pH sensitivity. In summary, our findings provide a novel molecular determinant for pH regulation of TRPM3. The inhibition of TRPM3 by protons may indicate an endogenous mechanism governing TRPM3 gating and its physiological/ pathological functions.
Signatures of processing complexity during global cognitive states in ventromedial prefrontal cortex
Authors: Mehta Priyanka S. , Michael Yoo Seng Bum , Hayden Benjamin Y.
Published: October 2020

Behavioral neuroscience almost exclusively studies behavior during tasks and ignores the unstructured inter-trial interval (ITI). However, it is unlikely that the ITI is simply an idling or paused mode; instead, it is a likely time for globally focused cognition, in which attention is disengaged from the task at hand and oriented more broadly. To gain insight into the computational underpinnings of globally focused cognition, we recorded from neurons in a core decision-making region, area 14 of ventromedial prefrontal cortex (vmPFC), as macaques performed a foraging search task with long inter-trial intervals (ITIs). We find that during the ITI, ensemble firing is associated with increased discriminability of a key mnemonic variable, recent reward rate, which in turn predicts upcoming search strategy. ITI activity is also associated with increased ensemble dimensionality and faster subspace reorganization, presumed markers of processing complexity. These results demonstrate the flexible nature of mnemonic processing and support the idea that the brain makes use of ostensible downtime to engage in complex processing.
A Machine Learning approach for assessing drug development risk
Authors: Vergetis Vangelis , Liaropoulos Gerasimos , Georganaki Maria , Dimakakos Andreas , Skaltsas Dimitrios , Gorgoulis Vassilis G , Tsirigos Aristotelis
Published: October 2020

Characterizing drug development risk – the probability that a drug will eventually receive regulatory approval – has been notoriously hard given the complexities of drug biology and clinical trials. This often leads to an inefficient allocation of resources, and an overall reduction in R&D productivity. We propose a Machine Learning (ML) approach that provides a more accurate and unbiased estimate of drug development risk than traditional models.
COVID-19 initial preparedness and response in Vietnam during the first six months of the pandemic and the lessons for Sendai framework implementation
Authors: Linh Tran Nu Quy , Hanh Tran Thi Tuyet , Shaw Rajib
Published: October 2020

Purpose

This paper aims to analyze the current responses applied in Vietnam to the Coronavirus disease (COVID-19) pandemic and link these measures to priority actions highlighted in the Sendai Framework for Disaster Risk Reduction (SFDRR). From there, strengths, limitations and recommendations on applying the SFDRR to build the pandemic resilience in the future are discussed.

Design/methodology/approach

The authors synthesize literature on response measures to the COVID-19 pandemic in Vietnam from January to June 2020 and compare to four priority actions of the SFDRR including understanding risk, strengthening governance, investing in risk reduction for resilience and enhancing preparedness for effective response and resilient recovery.

Findings

Vietnam has effectively controlled the pandemic with 401 infected cases and no death so far. Well preparation, timely policies’ implementation, risk communication and comprehensive approaches are key strategies. These measures are same as the four priority actions in the SFDRR.

Originality/value

To the best of the authors’ knowledge, this is the first study in Vietnam to link the COVID-19 response and the SFDRR, which can serve as an important example for other countries in responding to the pandemic. Some measures have surpassed SFDRR’s guidance, especially preventive responses applied nationwide with strong political will and the community’s commitment accompanied by sanctions. Cultural factors such as the habit of using masks to prevent air pollution have contributed to the good observance of wearing mask regulations during the pandemic. However, some areas that need more attention include specific solutions for vulnerable groups, limiting fake news and ensuring patient privacy.
Is agile the latest management fad? A review of success factors of agile transformations
Authors: Naslund Dag , Kale Rahul
Published: October 2020

Purpose

Agile is the new popular management change method and agile has lots of momentum. Management consulting firms are promoting agile via articles and newsletters. While history does not repeat itself, it often rhymes, and thus agile will probably be a successful change effort in some organizations. On the other hand, there is a high probability that agile will not deliver the expected results for most organizations. History reveals that about two-thirds of the change efforts are deemed unsuccessful – regardless of the actual change method. In this paper, we present the results of a systematic literature review on agile and we compare and contrast it with other similar organizational change methods. The purpose of this paper is to explore what one may learn from the history of the earlier change methods in terms of how organizations may succeed in their agile efforts.

Design/methodology/approach

The paper is based on a structured literature review of the agile concept – including agile transformation, and with a specific focus on critical success factors.

Findings

In addition to presenting the state of the art on agile in general, we identify, structure and categorize critical success factors (CSF) for agile. From the 13 categories, we form three clusters, which constitute a 3P framework (purpose, process and people). We also compare and contrast the CSF literature regarding agile with CSFs for organizational change in general. history indicates that most organizational change efforts are not successful. Based on the framework and the discussion, we provide recommendations to hopefully increase the probability of successful agile implementations.

Originality/value

Given the relative novelty or at least the renewed interest in agile, a structured literature review of the current status of this “new” method provides value as it may help organizations and managers to not repeat old mistakes – once again.
An exploration of the leadership strategies of Facebook community leaders
Authors: Gazit Tali , Bronstein Jenny
Published: October 2020

Purpose

Understanding leadership in newly created online social spaces, such Facebook communities, is an important new area of study within leadership research. This study explores an existing leadership model in offline environments by analyzing leadership strategies used by Facebook community leaders.

Design/methodology/approach

By using both quantitative and qualitative methods, data were collected through a survey from 94 Facebook community leaders about their leadership strategies.

Findings

Findings show that the framework of leadership behavior in offline groups can also be observed in Facebook communities. The content analysis of the open-ended questions reveals new categories reflecting unique leadership strategies in online environments. Leaders that participated in the study focused on strategies of content and team management, provided their groups with relevant content and personal stories to engage their members and strived to lead both offline and online-related social spaces to build a sense of community.

Originality/value

The growing number of Facebook community leaders and their key role in social media communities raise new questions about their position in light of what is already known about traditional leadership. Since social media occupies a central place in almost every aspect in everyday life, understanding the way that leaders manage these online communities is ever more important, and it can lead to an advancement in online communications.

Peer review

The peer review history for this article is available at:https://publons.com/publon/10.1108/OIR-01-2020-0034.
Processes at the soil–root interface determine the different responses of nutrient limitation and metal toxicity in forbs and grasses to nitrogen enrichment
Authors: Tian Qiuying , Lu Peng , Ma Pengfei , Zhou Huirong , Yang Ming , Zhai Xiufeng , Chen Mengmeng , Wang Hong , Li Wenchao , Bai Wenming , Lambers Hans , Zhang Wen‐Hao
Published: October 2020

Nutrient limitation and metal toxicity have been implicated in changes of grassland communities by nitrogen (N) deposition. Below‐ground processes, especially those at the soil–root interface, play important roles in determining variation in nutrient concentrations in plants. However, few studies have specifically focused on the roles of these processes in mineral‐element acquisition in grassland plants in response to N enrichment.

Here we investigated the contributions of below‐ground processes at the soil–root interface to the differential acquisition of phosphorus (P), calcium (Ca) and manganese (Mn) by forbs and grasses of a temperate steppe in response to N addition by combining field and glasshouse experiments.

Nitrogen addition increased the concentrations of both leaf P ([P]) and Mn ([Mn]) and decreased leaf [Ca] of forbs while it had little effects on leaf concentrations of these elements in grasses. Nitrogen addition led to a higher activity of acid phosphatase in the rhizosphere of forbs, and greater release of protons and carboxylates from forb roots than grass roots, contributing to the differential [P], [Ca] and [Mn] in the leaves of forbs and grasses. Applying oxalate to soil to simulate the release of carboxylates by N enrichment enhanced [P] and [Mn], and decreased [Ca] in the soil solution. However, addition of hydrogen‐ion increased [P], [Mn] and [Ca] in the soil solution. Lime addition mitigated the N‐addition‐induced soil acidification while it did not abolish the stimulatory effect of short‐term N addition on leaf [P] and [Mn] of forbs. Therefore, we conclude that differences in the eco‐physiological processes at the soil–root interface account for changes in leaf [P], [Ca] and [Mn] under short‐term N addition, and that soil acidification aggravates the responses of these elements, especially [Ca] and [Mn], to long‐term N enrichment.

Synthesis. Our results highlight the contribution of below‐ground processes, especially those at the soil–root interface, to variation in plant element concentrations between dominant forbs and grasses in the temperate steppe. These findings greatly enhance our mechanistic understanding of the effects of N deposition on grassland communities.
“It helped us, and it hurt us” The role of social media in shaping agency and action among youth in post‐disaster Nepal
Authors: Dahal Leena , Idris Mussa S. , Bravo Vanessa
Published: October 2020

This case study explores the communication platforms that youth in Nepal used to respond to the Gorkha earthquake that struck this country on 25 April 2015, and it delves into the role that social media played in shaping the relief efforts initialled and led by youth in Nepal. The data were collected through ethnographic fieldwork and 50 in‐depth interviews conducted in Nepal during the summers of 2015 and 2016 with Nepali youth directly involved in the relief efforts during the immediate aftermath. Findings show that Nepali youth served as integral agents of influence in the chaotic aftermath of the Gorkha earthquake, it highlights the various ways in which virtual communities mostly helped but (in some cases) hindered the relief distribution and coordination process, and it analyses how these 50 young people in Nepal conceptualized social media's role in shaping their agency and resilience. Implications are discussed on how the results of this case study can allow academics and practitioners gauge the effectiveness of social media platforms to respond to crises, understand their impact for people in distinct generations and evaluate the feasibility and inclusivity of using social media as a tool in national crises, especially in developing countries.
Pregnancy and childbirth outcomes as signposts to the future
Authors: Thorp John M
Published: October 2020

Deputy Editor‐in‐Chief, Dr John M Thorp, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/november-editorial-2020
Dermestes maculatus (Coleoptera: Dermestidae) development under fluoxetine effect using two drug administration models
Authors: Zanetti Noelia I. , Costantino Andrea , Lazzarini Natalia , Ferrero Adriana A. , Centeno Néstor D.
Published: October 2020

Fluoxetine is a selective serotonin reuptake inhibitor, commonly used for the treatment of a variety of psychopathological conditions. As such, fluoxetine may be expected to appear in clinical and forensic cases. Dermestes maculatus De Geer (Coleoptera: Dermestidae) has been recognized as a relevant component of the insect fauna associated with decomposing human and animal remains. Experiments were conducted to study the effect of fluoxetine on developing D. maculatus using two‐drug administration models: a non‐living animal model (pork muscle) and a living one (Sus scrofa L. pigs). We assessed the duration of immature stages and total life cycle, as well as morphological parameters (body length, cephalic width, and weight). The effect of fluoxetine was studied at an overdose concentration: In the non‐living animal model the drug was mixed with macerated pork muscle (2000 mg/kg) and in the living animal model, pigs were given the drug orally (833 mg/kg). A control was used for each model. Daily observations were performed from the beginning to the end of the experiments. GC‐MS was used for drug detection and quantification. There were no statistically significant differences in the duration of immature stages, life cycle, larval mortality, morphological parameters, or sex ratio, between treatment and control, regardless of the drug administration model. Given that fluoxetine had no detectable effect on the development of D. maculatus, detection of this drug in forensic situations would not compromise the accuracy of PMI estimations.
Lung adenocarcinoma in a patient with a cis EGFR L858R‐K860I doublet mutation identified using NGS‐based profiling test: Negative diagnosis on initial companion test and successful treatment with osimertinib
Authors: Onozawa Hiroto , Saito Haruhiro , Sunami Kuniko , Kubo Takashi , Yamamoto Noboru , Kasajima Rika , Ohtsu Takashi , Hiroshima Yukihiko , Kanamori Heiwa , Yokose Tomoyuki , Miyagi Yohei
Published: October 2020

Tyrosine kinase inhibitors are used as first‐line treatment for non‐small cell lung cancer (NSCLC) patients harboring driver mutations in EGFR, ALK, ROS1, and BRAF. Currently, standard molecular testing approaches help identify single genes for such targetable driver mutations in NSCLC; however, next‐generation sequencing (NGS)‐based genetic profiling provides a more comprehensive approach and is hence strongly recommended. This case study aimed to highlight the benefits of NGS‐based tests for the diagnosis of complex EGFR L858R mutations. A patient was diagnosed with stage IVB NSCLC using a government‐approved in vitro diagnostic test and was noted to have a high programmed death‐ligand 1 tumor proportion score. This patient was treated with pembrolizumab monotherapy followed by cisplatin and pemetrexed owing to the lack of actionable driver gene mutations, including EGFR mutations. After treatment failure, a sample harvested from the same transbronchial lung biopsy specimen (formalin‐fixed and paraffin‐embedded) used for the initial EGFR test was subjected to NGS‐based broad genetic profiling. The NGS‐based test identified an EGFR L858R‐K860I cis doublet mutation; however, neither of these mutations was identified upon initial molecular testing. The patient was then successfully treated with a third‐generation EGFR‐tyrosine kinase inhibitor, osimertinib. In this study, we delved deeper into the realm of L858R and K860I mutations in NSCLC and discuss the potential causes underlying our initial negative diagnosis. Furthermore, this study highlighted the additional benefits of replacing typical molecular tests with NGS‐based broad profiling approaches.

Key points

Significant findings of the study

The EGFR L858R‐K860I cis doublet mutation was not detected by a PCR‐based EGFR test.

A next generation sequencing (NGS)‐based test was able to identify the L858R‐K860I cis doublet mutation.

What this study adds

Osimertinib was effective in an NSCLC patient with EGFR L858R and K860I mutations.
Association between caregivers’ coping and children’s psychiatric symptoms in the heart transplantation process: A pilot study
Authors: Yilmaz Kafali Helin , Kalyoncu Tugba , Ozbaran Burcu , Kalyoncu Emir , Tuncer Osman Nuri , Ozturk Pelin , Engin Cagatay , Yagdi Tahir , Ulger Zulal , Atay Yuksel , Ozbaran Mustafa
Published: October 2020

Our aim was to investigate whether there is an association between caregivers’ coping and children's psychiatric symptoms and quality of life in adolescent heart transplant (HTx) recipients and HTx candidates with left ventricular assist device (LVAD). Fourteen patients were recruited for this pilot study (HTx (n = 8), LVAD (n = 6)). Schedule for Affective Disorders and Schizophrenia for School Aged Children, Present and Lifetime Version (K‐SADS) was administered to detect the psychiatric diagnosis of patients. Children's Depression Inventory (CDI), State‐Trait Anxiety Inventory, and Pediatric Quality of Life Inventory (PedsQL) were completed by adolescents; Brief Coping Styles Inventory by their caregivers. Six of the participants had an internalizing disorder. Optimistic coping strategy score was significantly higher in the caregivers of adolescents without an internalizing disorder than caregivers of those with an internalizing disorder (U = 2.500, P = .005). Utilizing Spearman's correlation, caregivers’ optimistic approach (rho = −0.736, P = .004), and self‐confident approach (rho = −0.634, P = .020) had significant negative correlations with children's CDI scores. Moreover, caregivers’ optimistic approach score had a significant positive correlation with children's PedsQL score (rho = 0.563, P = .045). According to our preliminary results, it seems that caregivers’ optimistic and self‐confident coping strategies may be associated with fewer internalizing symptoms and a better quality of life in adolescents in the HTx process. A future multicentered longitudinal study will be planned to assess the effect of caregivers’ coping strategies on the psychological adjustment of these children.
The Evolution of the ṣāraʿat Ritual in Leviticus 13:1‐46
Authors: Skidmore Simon
Published: October 2020

The problematic assumption that biblical purity thematically represents life and death is commonly held within modern biblical studies. Building upon this assumption, many scholars have attempted to explain the treatment of the ṣāraʿat patient in Leviticus 13:1‐46 as a symbolic banishment of death. However, the current paper attempts to move beyond this reading towards a method of reconstructing the evolution of biblical rituals and practices. Through the utilisation of René Girard’s four scapegoat stereotypes, the current paper identifies the scapegoat mechanism in Leviticus 13:1‐46, and reconstructs a proposed evolution of this ritual. This paper suggests that the ritual presented in Leviticus 13:1‐46 may have evolved from an earlier tradition, in which ṣāraʿat patients were executed to halt a mimetic crisis.
Placental maternally expressed gene 3 differentially methylated region methylation profile is associated with maternal glucose concentration and newborn birthweight
Authors: Chen Cheng , Jiang Ying , Yan Ting , Chen Yuan , Yang Mengmeng , Lv Min , Xi Fangfang , Lu Juefei , Zhao Baihui , Luo Qiong
Published: October 2020

Aims/Introduction

Emerging evidence shows that epigenetic modifications occurring during fetal development in response to intrauterine exposures could be one of the mechanisms involved in the early determinants of adult metabolic disorders. This study aimed to investigate whether the placental maternally expressed gene 3 (MEG3) deoxyribonucleic acid (DNA) methylation profile is associated with maternal gestational diabetes mellitus status and newborn birthweight.

Materials and Methods

Samples for measurement were collected from 23 women with gestational diabetes mellitus and 23 healthy controls. MEG3 gene expression and DNA methylation levels were assessed using quantitative real‐time polymerase chain reaction and MethylTargetTM, respectively. Pearson correlation analyses were used to examine associations between placental DNA methylation levels and clinical variables of interest. The associated results were adjusted by multivariate linear regression for maternal age, body mass index, height, gestational age and newborn sex as confounders.

Results

We found that the DNA methylation levels in the MEG3 differentially methylated region were significantly different between the gestational diabetes mellitus and control groups on the maternal side of the placenta (40.64 ± 2.15 vs 38.33 ± 2.92; P = 0.004). Furthermore, the mean MEG3 DNA methylation levels were correlated positively with maternal fasting glucose concentrations (R = 0.603, P < 0.001) and newborn birthweight (R = 0.568, P < 0.001).

Conclusions

The placental DNA methylation status in the MEG3 differentially methylated region was correlated with maternal glucose concentrations and newborn birthweight. These epigenetic adaptations might contribute to late‐onset obesity, underlining the adverse intrauterine environment.
Development, behaviour and sensory processing in Marshall–Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes
Authors: Mulder P. A. , van Balkom I. D. C. , Landlust A. M. , Priolo M. , Menke L. A. , Acero I. H. , Alkuraya F. S. , Arias P. , Bernardini L. , Bijlsma E. K. , Cole T. , Coubes C. , Dapia I. , Davies S. , Di Donato N. , Elcioglu N. H. , Fahrner J. A. , Foster A. , González N. G. , Huber I. , Iascone M. , Kaiser A.‐S. , Kamath A. , Kooblall K. , Lapunzina P. , Liebelt J. , Lynch S. A. , Maas S. M. , Mammì C. , Mathijssen I. B. , McKee S. , Mirzaa G. M. , Montgomery T. , Neubauer D. , Neumann T. E. , Pintomalli L. , Pisanti M. A. , Plomp A. S. , Price S. , Salter C. , Santos‐Simarro F. , Sarda P. , Schanze D. , Segovia M. , Shaw‐Smith C. , Smithson S. , Suri M. , Tatton‐Brown K. , Tenorio J. , Thakker R. V. , Valdez R. M. , Van Haeringen A. , Van Hagen J. M. , Zenker M. , Zollino M. , Dunn W. W. , Piening S. , Hennekam R. C.
Published: October 2020

Background

Ultrarare Marshall–Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross‐sectional study, and results are presented with genetic findings.

Methods

Behavioural phenotypes are compared of eight individuals with Marshall‐Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long‐term follow‐up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall–Smith syndrome.

Results

Marshall–Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow‐up measurement of cognition and adaptive behaviour in Marshall–Smith syndrome shows different individual learning curves over time.

Conclusions

Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person‐environment fit.
Family monetary incentives as a value‐based care model for oral hygiene: rationale and design of the BEhavioral EConomics for Oral health iNnovation (BEECON) trial
Authors: Ramos‐Gomez Francisco , White Justin S. , Lindau Helen E. , Lin Tracy K. , Finlayson Tracy L. , Liu Jenny X. , Gansky Stuart A.
Published: October 2020

Background

Effective prevention‐focused, value‐based strategies are needed to improve oral health. Despite evidence that monetary incentives can motivate healthy behavior, well‐powered studies have yet to examine incentives for improving children's oral hygiene.

Aim

Describe the rationale and design of the BEhavioral EConomics for Oral health iNnovation (BEECON) trial, which tests lottery‐based monetary incentives as a consumer‐oriented, value‐based care model for improving children's oral hygiene.

Design

Phase II, stratified, permuted block randomized, controlled, two‐arm, parallel groups, prevention trial.

Setting

Study visits occur at three Los Angeles, CA health clinics.

Participants

Two hundred and forty‐four parent‐child dyads with a child aged 6‐48 months.

Interventions

Eligible dyads were randomized in equal allocation to one of two groups: lottery incentive group or waitlist (delayed incentive) control group. Weekly lottery incentives were offered for 6 months based on Bluetooth‐recorded toothbrushing frequency. Both groups received weekly text message feedback on toothbrushing performance.

Outcomes

The primary outcome was toothbrushing performance from baseline to 6 months, measured as the mean number of qualifying half‐day Bluetooth‐recorded episodes per week when the child's teeth were brushed. Secondary outcomes included toothbrushing performance sustainability through 12 months and dental caries status.

Conclusions

BEECON offers a consumer‐oriented approach to promoting value‐based oral health care. We hypothesize that lottery‐based incentives can improve oral hygiene in young children. Study results will inform programming efforts to enhance oral disease prevention in young children.

Trial Registration

ClinicalTrials.gov identifier NCT03576326.