bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-biofouling NH3 gas sensor based on reentrant thorny ZnO/graphene hybrid nanowalls
Authors: Hang Tian , Wu Jiangming , Xiao Shuai , Li Baohong , Li Hongbo , Yang Chengduan , Yang Cheng , Hu Ning , Xu Yonghang , Zhang Yu , Xie Xi
Published: July 2020

Since toxic gas leakage may cause ecological environmental problems and even life-threatening damage, effective monitoring of toxic gas is of great importance and subject to increasing demand. However, complicated environmental factors, as well as various coexisting interferences can easily affect the sensitivity and selectivity of gas sensors, hindering their performance. Recent reports have successfully demonstrated the development of hierarchical nanostructures with desirable self-cleaning properties, yet gas sensors that can resist contamination have rarely been realized. Here, we developed a reentrant thorny ZnO/graphene hybrid nanowall structure that simultaneously repels liquid contamination and possesses NH3 gas sensing properties. The unique reentrant and hierarchical structure, featuring an interconnected vertical graphene nanowall framework with numerous ZnO nanospikes branched on the top nanowall, is highly repellent to liquids, even biofluids with low surface tension. The hierarchical structure consisting of gas sensing graphene and ZnO can be successfully applied as an NH3 gas sensor at room temperature, exhibiting not only excellent sensitivity, selectivity, and repeatability, but also outstanding stability even after bacterial contamination. This study provides a versatile method for fabricating reentrant and hierarchical structures with excellent liquid repellency, and offers a promising method for designing reliable gas sensors with anti-biofouling properties.
Flexible, diamond-based microelectrodes fabricated using the diamond growth side for neural sensing
Authors: Fan Bin , Rusinek Cory A. , Thompson Cort H. , Setien Monica , Guo Yue , Rechenberg Robert , Gong Yan , Weber Arthur J. , Becker Michael F. , Purcell Erin , Li Wen
Published: July 2020

Diamond possesses many favorable properties for biochemical sensors, including biocompatibility, chemical inertness, resistance to biofouling, an extremely wide potential window, and low double-layer capacitance. The hardness of diamond, however, has hindered its applications in neural implants due to the mechanical property mismatch between diamond and soft nervous tissues. Here, we present a flexible, diamond-based microelectrode probe consisting of multichannel boron-doped polycrystalline diamond (BDD) microelectrodes on a soft Parylene C substrate. We developed and optimized a wafer-scale fabrication approach that allows the use of the growth side of the BDD thin film as the sensing surface. Compared to the nucleation surface, the BDD growth side exhibited a rougher morphology, a highersp3content, a wider water potential window, and a lower background current. The dopamine (DA) sensing capability of the BDD growth surface electrodes was validated in a 1.0 mM DA solution, which shows better sensitivity and stability than the BDD nucleation surface electrodes. The results of these comparative studies suggest that using the BDD growth surface for making implantable microelectrodes has significant advantages in terms of the sensitivity, selectivity, and stability of a neural implant. Furthermore, we validated the functionality of the BDD growth side electrodes for neural recordings both in vitro and in vivo. The biocompatibility of the microcrystalline diamond film was also assessed in vitro using rat cortical neuron cultures.
Neurodevelopmental impairment induced by prenatal valproic acid exposure shown with the human cortical organoid-on-a-chip model
Authors: Cui Kangli , Wang Yaqing , Zhu Yujuan , Tao Tingting , Yin Fangchao , Guo Yaqiong , Liu Haitao , Li Fei , Wang Peng , Chen Yuejun , Qin Jianhua
Published: July 2020

Prenatal exposure to environmental insults can increase the risk of developing neurodevelopmental disorders. Administration of the antiepileptic drug valproic acid (VPA) during pregnancy is tightly associated with a high risk of neurological disorders in offspring. However, the lack of an ideal human model hinders our comprehensive understanding of the impact of VPA exposure on fetal brain development, especially in early gestation. Herein, we present the first report indicating the effects of VPA on brain development at early stages using engineered cortical organoids from human induced pluripotent stem cells (hiPSCs). Cortical organoids were generated on micropillar arrays in a controlled manner, recapitulating the critical features of human brain development during early gestation. With VPA exposure, cortical organoids exhibited neurodevelopmental dysfunction characterized by increased neuron progenitors, inhibited neuronal differentiation and altered forebrain regionalization. Transcriptome analysis showed new markedly altered genes (e.g., KLHL1, LHX9, and MGARP) and a large number of differential expression genes (DEGs), some of which are related to autism. In particular, comparison of transcriptome data via GSEA and correlation analysis revealed the high similarity between VPA-exposed organoids with the postmortem ASD brain and autism patient-derived organoids, implying the high risk of autism with prenatal VPA exposure, even in early gestation. These new findings facilitate a better understanding of the cellular and molecular mechanisms underlying postnatal brain disorders (such as autism) with prenatal VPA exposure. This established cortical organoid-on-a-chip platform is valuable for probing neurodevelopmental disorders under environmental exposure and can be extended to applications in the study of diseases and drug testing.
Digital health data-driven approaches to understand human behavior
Authors: Marsch Lisa A.
Published: July 2020

Advances in digital technologies and data analytics have created unparalleled opportunities to assess and modify health behavior and thus accelerate the ability of science to understand and contribute to improved health behavior and health outcomes. Digital health data capture the richness and granularity of individuals’ behavior, the confluence of factors that impact behavior in the moment, and the within-individual evolution of behavior over time. These data may contribute to discovery science by revealing digital markers of health/risk behavior as well as translational science by informing personalized and timely models of intervention delivery. And they may help inform diagnostic classification of clinically problematic behavior and the clinical trajectories of diagnosable disorders over time. This manuscript provides a review of the state of the science of digital health data-driven approaches to understanding human behavior. It reviews methods of digital health assessment and sources of digital health data. It provides a synthesis of the scientific literature evaluating how digitally derived empirical data can inform our understanding of health behavior, with a particular focus on understanding the assessment, diagnosis and clinical trajectories of psychiatric disorders. And, it concludes with a discussion of future directions and timely opportunities in this line of research and its clinical application.
Intranasal oxytocin increases heart-rate variability in men at clinical high risk for psychosis: a proof-of-concept study
Authors: Martins Daniel , Davies Cathy , De Micheli Andrea , Oliver Dominic , Krawczun-Rygmaczewska Alicja , Fusar-Poli Paolo , Paloyelis Yannis
Published: July 2020

Autonomic nervous system (ANS) dysfunction (i.e., increased sympathetic and/or decreased parasympathetic activity) has been proposed to contribute to psychosis vulnerability. Yet, we still lack directed therapeutic strategies that improve ANS regulation in psychosis or at-risk states. The oxytocin system constitutes a potential therapeutic target, given its role in ANS regulation. However, whether intranasal oxytocin ameliorates autonomic regulation during emerging psychosis is currently unknown. We pooled together two datasets, one of 30 men at clinical high risk for psychosis (CHR-P), and another of 17 healthy men, who had participated in two double-blinded, placebo-controlled, randomised, crossover MRI studies with similar protocols. All participants self-administered 40 IU of intranasal oxytocin or placebo using a nasal spray. We recorded pulse plethysmography during a period of 8 min at about 1 h post dosing and estimated heart rate (HR) and high-frequency HR variability (HF-HRV), an index of cardio-parasympathetic activity. CHR-P and healthy men did not differ at resting HR or HF-HRV under placebo. We found a significant condition × treatment effect for HF-HRV, showing that intranasal oxytocin, compared with placebo, increased HF-HRV in CHR-P but not in healthy men. The main effects of treatment and condition were not significant. In this proof-of-concept study, we show that intranasal oxytocin increases cardio-parasympathetic activity in CHR-P men, highlighting its therapeutic potential to improve autonomic regulation in this clinical group. Our findings support the need for further research on the preventive and therapeutic potential of intranasal oxytocin during emerging psychosis, where we lack effective treatments.
LncRNA SNHG15 regulates EGFR-TKI acquired resistance in lung adenocarcinoma through sponging miR-451 to upregulate MDR-1
Authors: Huang Jiayuan , Pan Banzhou , Xia Guohao , Zhu Jingni , Li Chenchen , Feng Jifeng
Published: July 2020

Lung adenocarcinoma (LUAD) is the main component of non-small-cell lung cancer (NSCLC) and causes a great health concern globally. The top priority of LUAD treatment is to deal with gefitinib resistance. Long non-coding RNAs are certified to modify gefitinib resistance in the course of tumor aggravation. The study focuses on addressing the function of small nucleolar RNA host gene 15 (SNHG15) on modifying gefitinib resistance in LUAD. Previously, NOTCH pathway is implicated in LUAD chemo-resistance. SNHG15 level was boosted following the depletion of NOTCH-1 in A549/GR and H1975/GR cells. Functional studies indicated that SNHG15 and multidrug resistance protein 1 (MDR-1) were overexpressed and possess tumor-promoting functions in gefitinib-resistant LUAD cells while miR-451 was downregulated and possess tumor-suppressive behaviors in gefitinib-resistant LUAD cells. Mechanically, the SNHG15 was cytoplasmically distributed in GR LUAD cells. In addition, SNHG15 released MDR-1 from the suppression of miR-451, leading to MDR-1 promotion. In addition, the elevation of SNHG15 could be attributed to ZEB1. Rescue assays highlighted that downstream molecules MDR-1 and miR-451 could reverse the effects of SNHG15 downregulation on gefitinib-resistant LUAD cells. SNHG15 could alter chemo-resistance of LUAD cells to Gefitinib via regulating miR-451/MDR-1, which could be inspiring findings for the advancement of chemo-therapies for LUAD.
Echinatin suppresses esophageal cancer tumor growth and invasion through inducing AKT/mTOR-dependent autophagy and apoptosis
Authors: Hong Pan , Liu Qin-Wen , Xie Yao , Zhang Qi-Hua , Liao Long , He Qing-Yu , Li Bin , Xu Wen Wen
Published: July 2020

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor survival. It is urgent to search for new efficient drugs with good stability and safety for clinical therapy. This study aims to identify potential anticancer drugs from a compound library consisting of 429 natural products. Echinatin, a compound isolated from the Chinese herb Glycyrrhiza uralensis Fisch, was found to markedly induce apoptosis and inhibit proliferation and colony-formation ability in ESCC. Confocal fluorescence microscopy data showed that echinatin significantly induced autophagy in ESCC cells, and autophagy inhibitor bafilomycinA1 attenuated the suppressive effects of echinatin on cell viability and apoptosis. Mechanistically, RNA sequencing coupled with bioinformatics analysis and a series of functional assays revealed that echinatin induced apoptosis and autophagy through inactivation of AKT/mTOR signaling pathway, whereas constitutive activation of AKT significantly abrogated these effects. Furthermore, we demonstrated that echinatin had a significant antitumor effect in the tumor xenograft model and markedly suppressed cell migration and invasion abilities of ESCC cells in a dose-dependent manner. Our findings provide the first evidence that echinatin could be a novel therapeutic strategy for treating ESCC.
Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration
Authors: Wei Xiaowei , Ma Wei , Gu Hui , Liu Dan , Luo Wenting , Bai Yuzuo , Wang Weilin , Lui Vincent Chi Hang , Yang Peixin , Yuan Zhengwei
Published: July 2020

Neural tube defects (NTDs) lead to prenatal mortality and lifelong morbidity. Currently, surgical closure of NTD lesions results in limited functional recovery. We previously suggested that nerve regeneration was critical for NTD therapy. Here, we report that transamniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for NTDs during early development may achieve beneficial functional recovery. In our ex vivo rat embryonic NTD model, BMSCs injected into the amniotic cavity spontaneously migrated into the defective neural tissue. Hepatocyte growth factor and its receptor c-MET were found to play critical roles in this NTD lesion-specific migration. Using the in vivo rat fetal NTD model, we further discovered that the engrafted BMSCs specifically differentiated into the cell types of the defective tissue, including skin and different types of neurons in situ. BMSC treatment triggered skin repair in fetuses, leading to a 29.9 ± 5.6% reduction in the skin lesion area. The electrophysiological functional recovery assay revealed a decreased latency and increased motor-evoked potential amplitude in the BMSC-treated fetuses. Based on these positive outcomes, ease of operation, and reduced trauma to the mother and fetus, we propose that transamniotic BMSC administration could be a new effective therapy for NTDs.
Decarboxylative Umpolung Synthesis of Amines from Carbonyl Compounds
Authors: Zhao Baoguo , Chen Wen-Wen
Published: July 2020

2-Azaallyl anions are valuable intermediates which have versatile applications in functionalization with various electrophiles. Decarboxylation of the imines formed from aromatic aldehydes and α,α-diphenylglycine provides an interesting and efficient way to generate delocalized 2-azaallyl anions, which display high reactivity toward different electrophiles with excellent regioselectivity at the diphenylketimino aryl carbon of the 2-azaallyl anions. The transformation produces various amines in good yields under very mild conditions. This Synpacts article highlights the recent advances on the decarboxylative umpolung synthesis of amines from carbonyl compounds.

1 Introduction

2 Decarboxylative Umpolung Reactions of Carbonyl Compounds with Different Electrophiles

2.1 Reaction with π-Allyl–Pd(II) Species

2.2 Reaction with Morita–Baylis–Hillman Adducts

2.3 Reaction with Imines

2.3.1 Intermolecular Reaction with N-Ts Imines

2.3.2 Intramolecular Reaction with Chiral N-tert-Butanesulfinyl Imines

2.4 Reaction with Aldehydes and Ketones

3 Decarboxylative Umpolung Reaction of α,β-Unsaturated Aldehydes with Aldehydes

4 Conclusion
Complete Resection of a Large Mediastinal Calcifying Fibrous Tumor
Authors: Bono Géraldine L. P. , Lehner Markus , Schilling Freimut H. , Stahr Nikolai , Nowack Miriam , Szavay Philipp O.
Published: July 2020

Calcifying fibrous tumor (CFT) is a benign tumor entity which can present in a variety of different sites. Till date, eight cases with a mediastinal manifestation have been published in literature. Surgical removal is the treatment of choice for this often incidentally detected tumor. Surgery of thoracic CFT may be challenging due to its localization within the mediastinum. A 10-year old boy with a right-sided thoracic pectus carinatum-like deformity was referred for further evaluation, incidentally, revealing a mediastinal mass in computed tomography (CT). Laboratory results were all within normal range. Magnetic resonance imaging (MRI) showed a large tumor in the upper anterior mediastinum suggesting expansive but not infiltrative character. The tumor was displacing surrounding structures like the heart and the diaphragm. Lower venous stasis with dilation of the inferior cava vein could be demonstrated. The tumor was considered to be of benign dignity and surgical removal was indicated. Complete tumor resection could be achieved through a sternotomy approach, along with thymectomy. A partial resection of both the pericardium and diaphragm was required due to adhesion with soft tissue at those sites. The specimen's size was 320 mm × 145 mm × 100 mm, histologically confirmed as CFT. The patient showed no residual tumor at 3- and 9-month follow-up. This case is a report on a large mediastinal CFT which underwent successful complete surgical removal. Following tumor resection, prognosis is considered to be good; however, key issue is complete resection to avoid local tumor recurrence.
Clinical Quiz: Reconstructive Strategies in a 5-Month-Old Infant with a Cloaca
Authors: Lane Victoria A. , Levitt Marc A.
Published: July 2020

Herein we present a case of 5-month-old female born with a cloaca. She underwent a colostomy at birth and then underwent endoscopy and cloacagram to plan for the definitive reconstruction. The case is presented with a focus on the reconstructive strategies, and questions for the readers are posed in a quiz format.
Reasons for Hospitalization of Patients with Acute Pulmonary Embolism Based on the Hestia Decision Rule
Authors: Hendriks Stephan V. , den Exter Paul L. , Zondag Wendy , Brouwer Rolf , Eijsvogel Michiel , Grootenboers Marco J. , Faber Laura M. , Heller-Baan Roxanne , Hofstee Herman M. A. , Iglesias del Sol Antonio , Kruip Marieke J. H. A. , Mairuhu Albert T. A. , Melissant Christian F. , Peltenburg Henny G. , van de Ree Marcel A. , Serné Erik H. , Huisman Menno V. , Klok Frederikus A. ,   on behalf of the Hestia/Vesta investigators
Published: July 2020

Background The Hestia criteria can be used to select pulmonary embolism (PE) patients for outpatient treatment. The subjective Hestia criterion “medical/social reason for admission” allows the treating physician to consider any patient-specific circumstances in the final management decision. It is unknown how often and why this criterion is scored.

Methods This is a patient-level post hoc analysis of the combined Hestia and Vesta studies. The main outcomes were the frequency of all scored Hestia items in hospitalized patients and the explicit reason for scoring the subjective criterion. Hemodynamic parameters and computed tomography-assessed right ventricular (RV)/left ventricular (LV) ratio of those only awarded with the subjective criterion were compared with patients treated at home.

Results From the 1,166 patients screened, data were available for all 600 who were hospitalized. Most were hospitalized to receive oxygen therapy (45%); 227 (38%) were only awarded with the subjective criterion, of whom 51 because of “intermediate to intermediate-high risk PE.” Compared with patients with intermediate risk PE (RV/LV ratio > 1.0) treated at home (179/566, 32%), hospitalized patients with only the subjective criterion had a higher mean RV/LV ratio (mean difference +0.30, 95% confidence interval [CI] 0.19–0.41) and a higher heart rate (+18/min, 95% CI 10–25). No relevant differences were observed for other hemodynamic parameters.

Conclusion The most frequent reason for hospital admission was oxygen therapy. In the decision to award the subjective criterion as sole argument for admission, the severity of the RV overload and resulting hemodynamic response of the patient was taken into account rather than just abnormal RV/LV ratio.
Current Avenues for COVID-19 Serology
Authors: Srivastava Saumya , Jain Vidhi , Nag Vijaya Lakshmi , Misra Sanjeev , Singh Kuldeep
Published: July 2020

Development of rapid, reliable, and easy diagnostic tests with high-throughput is the need of the hour for laboratories combating the COVID-19 pandemic. While real-time polymerase chain reaction (RT-PCR) is the gold standard for diagnosing active infections, it is expensive and time-consuming. Serological diagnostic assays with a premise to aid rapid contact tracing, immune status determination, and identification of potential convalescent plasma donors hold great promise. Timely diagnosis, effective treatment, and future prevention are key to management of COVID-19.
Molecular Diagnosis of COVID-19: An Update and Review
Authors: Priyadarshi Ketan , Nag Vijaya Lakshmi , Kombade Sarika P. , Gadepalli Ravi Sekhar , Misra Sanjeev , Singh Kuldeep
Published: July 2020

SARS-CoV-2 belongs to genus Betacoronavirus subgenus Sarbecovirus of the family Coronaviridae, which originated as a global public health problem. The disease caused is termed as Coronavirus Disease (COVID-19). The virus spread in more than 213 countries and territories all over the world and disease was declared as a pandemic. SARS-CoV-2 is an enveloped positive-sense single- stranded ribonucleic acid (ssRNA) virus. Severe infection and high-mortality are seen in patients with comorbid conditions like diabetes, hypertension, cancer, old age, malnutrition, children, and pregnancy. In India, strategy for testing of COVID-19 has been framed and revised over the course of time by the Indian Council of Medical Research (ICMR), Department of Health Research (DHR), Ministry of Health and Family Welfare (MOHFW), Government of India. ICMR has created a network of viral research and diagnostic laboratories (VRDLs) all over the country, and COVID-19 testing has also been undertaken by ICMR. AIIMS Jodhpur is a regional level VRDL, mentoring 38 government and private laboratories for molecular diagnosis of COVID-19 in the states of Rajasthan and Gujarat. Currently, real-time reverse transcription polymerase chain reaction (rRT-PCR) assay is used all over the country for diagnosis of COVID-19. It uses the TaqMan fluorogenic probe-based chemistry and 5′- nuclease activity of Taq DNA polymerase. It targets specific genes like the RdRp gene, HKU-Orf1ab gene, E gene, and N gene. Apart from rRT-PCR, other isothermal nucleic acid test (NAT)-like transcription-mediated amplification (TMA), loop-mediated isothermal amplification (LAMP), etc. are emerging diagnostic tools to detect COVID-19. Cepheid Xpert Xpress SARS- CoV-2 test and Truenat betaCoV are point-of-care molecular assays which gives results in less than 1 hour, and helps to provide rapid and accurate results. Automated molecular assays like Cobas SARS-CoV-2 and Multiplex NAAT BioFire Respiratory Panel 2.1 (RP2.1) are newer techniques to curb the disease. Sherlock CRISPR SARS-CoV-2 kit is a highly specific and sensitive assay developed to diagnose COVID-19. rRT-PCR has been combined with techniques like bead hybridization, digital droplet PCR, microarray, etc. for improving the correct diagnosis. Recent molecular assays are the future pillars for containment of COVID-19 outbreaks all over the world.
Coronavirus and Cardiovascular System
Authors: Parekh Sandeep , Talwar Kewal Krishan
Published: July 2020

With the pandemic of COVID-19 infection spreading throughout the world leading to unprecedented serious burden on healthcare, our understanding of the virus continues to grow on a daily basis with the whole world united to find a vaccine/cure to combat the disease. Clinical experience with growing number of cases has provided us with insight into the pathophysiology of the disease and the various systems of the body it affects. The growing experience shows that cardiovascular complications occur in significant number of cases and contribute to increased mortality. The complications and mortality is also higher in those with pre-existing cardiovascular disease. The pathogenesis of increased cardiac complications is possibly related to the action of virus surface spike proteins through ACE2 receptors expressed in the myocardium. Although various drugs/therapies are being tried currently, no effective therapy is still available. It is emphasized that those with existing cardiac disease should optimally take their medicines, and religiously follow preventive measures like social distancing, self-isolation and hand hygiene.
Interpopulation variation in germination response to fire-related cues and after-ripening in seeds of the evergreen perennial Anigozanthos flavidus (Haemodoraceae)
Authors: Ma Hongyuan , Erickson Todd E. , Walck Jeffrey L. , Merritt David J.
Published: July 2020

Variations in the degree of seed dormancy expressed among conspecific populations provide a basis for improving understanding of the mechanisms controlling species persistence, especially in fire-prone ecosystems. We investigated seed germination of 12 Anigozanthos flavidus populations in response to various fire-related cues that included exposure to karrikinolide, glyceronitrile and smoke water at five temperatures, and the effects of heat shock and its interaction with glyceronitrile. Seeds from populations with deep-degree dormancy (DD) and light-degree dormancy (LD) were subjected to 0–8 months of after-ripening, and the viability of the ungerminated seeds was tested. The degree of seed dormancy and responses to fire-related cues were highly variable among populations. Glyceronitrile and smoke water significantly improved germination in 12 and 8 populations respectively. Heat significantly enhanced germination in all populations, but was less effective when combined with glyceronitrile. After-ripening for 3 months increased germination, whereas ≥4 months led to secondary dormancy or loss of viability. Loss of viability was greater for DD than for LD seeds. Interpopulation variations in the degree of seed dormancy, seed germination requirements for fire-related cues and germination viability in response to after-ripening in A. flavidus contribute to persistence in the variable and unpredictable Mediterranean environment.
Adjunctive Daptomycin in the Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Randomized, Controlled Trial
Authors: Cheng Matthew P , Lawandi Alexander , Butler-Laporte Guillaume , De l’Étoile-Morel Samuel , Paquette Katryn , Lee Todd C
Published: July 2020

Background

Bloodstream infections (BSIs) with methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. Our objective in this study was to determine the efficacy of synergistic treatment with daptomycin when given with either cefazolin or cloxacillin for the treatment of MSSA BSI.

Methods

A randomized, double-blind, placebo-controlled trial was performed at 2 academic hospitals in Montreal, Canada. Patients aged ≥18 years with MSSA BSI receiving either cefazolin or cloxacillin monotherapy were considered for inclusion. In addition to the standard-of-care treatment, participants received a 5-day course of adjunctive daptomycin or placebo. The primary outcome was the duration of MSSA BSI in days.

Results

Of 318 participants screened, 115 were enrolled and 104 were included in the intention-to-treat analysis (median age, 67 years; 34.5% female). The median duration of bacteremia was 2.04 days among patients who received daptomycin vs 1.65 days in those who received placebo (absolute difference, 0.39 days; P = .40). In a modified intention-to-treat analysis that involved participants who remained bacteremic at the time of enrollment, we found a median duration of bacteremia of 3.06 days among patients who received daptomycin vs 3.0 days in those who received placebo (absolute difference, 0.06 days; P = .77). Ninety-day mortality in the daptomycin arm was 18.9% vs 17.7% in the placebo arm (P = 1.0).

Conclusions

Among patients with MSSA BSIs, the administration of adjunctive daptomycin therapy to standard-of-care treatment did not shorten the duration of bacteremia and should not be routinely considered.

Clinical Trials Registration

NCT02972983.
A Modern View on Forward Security
Authors: Boyd Colin , Gellert Kai
Published: July 2020

Forward security ensures that compromise of entities today does not impact the security of cryptographic primitives employed in the past. Such a form of security is regarded as increasingly important in the modern world due to the existence of adversaries with mass storage capabilities and powerful infiltration abilities. Although the idea of forward security has been known for over 30 years, current understanding of what it really should mean is limited due to the prevalence of new techniques and inconsistent terminology. We survey existing methods for achieving forward security for different cryptographic primitives and propose new definitions and terminology aimed at a unified treatment of the notion.
Beyond survival experiments: using biomarkers of oxidative stress and neurotoxicity to assess vulnerability of subterranean fauna to climate change
Authors: Pallarés Susana , Sanchez-Hernandez Juan C , Colado Raquel , Balart-García Pau , Comas Jordi , Sánchez-Fernández David
Published: July 2020

Accurate assessments of species vulnerability to climate change need to consider the physiological capacity of organisms to deal with temperature changes and identify early signs of thermally induced stress. Oxidative stress biomarkers and acetylcholinesterase activity are useful proxies of stress at the cellular and nervous system level. Such responses are especially relevant for poor dispersal organisms with limited capacity for behavioural thermoregulation, like deep subterranean species. We combined experimental measurements of upper lethal thermal limits, acclimation capacity and biomarkers of oxidative stress and neurotoxicity to assess the impact of heat stress (20°C) at different exposure times (2 and 7 days) on the Iberian endemic subterranean beetle Parvospeonomus canyellesi. Survival response (7 days of exposure) was similar to that reported for other subterranean specialist beetles (high survival up to 20°C but no above 23°C). However, a low physiological plasticity (i.e. incapacity to increase heat tolerance via acclimation) and signs of impairment at the cellular and nervous system level were observed after 7 days of exposure at 20°C. Such sublethal effects were identified by significant differences in total antioxidant capacity, glutathione S-transferase activity, the ratio of reduced to oxidized forms of glutathione and acetylcholinesterase activity between the control (cave temperature) and 20°C treatment. At 2 days of exposure, most biomarker values indicated some degree of oxidative stress in both the control and high-temperature treatment, likely reflecting an initial altered physiological status associated to factors other than temperature. Considering these integrated responses and the predicted increase in temperature in its unique locality, P. canyellesi would have a narrower thermal safety margin to face climate change than that obtained considering only survival experiments. Our results highlight the importance of exploring thermally sensitive processes at different levels of biological organization to obtain more accurate estimates of the species capacity to face climate change.
The Ups and Downs of Daily Life During COVID-19: Age Differences in Affect, Stress, and Positive Events
Authors: Klaiber Patrick , Wen Jin H , DeLongis Anita , Sin Nancy L
Published: July 2020

Objectives

Past research has linked older age with greater emotional well-being and decreased reactivity to stressors, but it is unknown whether age-related advantages in emotional well-being are maintained in the wake of COVID-19. We examined age differences in exposure and affective reactivity to daily stressors and positive events in the first several weeks of the COVID-19 outbreak.

Methods

In March and April 2020, 776 adults from Canada and the United States aged 18–91 (mean age 45) years reported COVID-19 threats at baseline, then completed nightly surveys for 1 week about their daily stressors, positive events, and affect.

Results

Younger age predicted more concerns about the threat of COVID-19 across multiple domains, in addition to lower positive affect, higher negative affect, and less frequent positive events. Younger adults had more non-COVID-19 daily stressors and higher perceived control over stressors, but lower perceived coping efficacy than older adults. There were no age differences in the frequency of COVID-19 daily stressors nor perceived stressor severity. Younger adults had greater reductions in negative affect on days when more positive events occurred and greater increases in negative affect on days when non-COVID-19 stressors occurred. Age moderation was attenuated for negative affective reactivity to COVID-19 stressors. Age did not moderate positive affective reactivity to daily events.

Discussion

In the early weeks of the pandemic, older adults showed better emotional well-being and less reactivity to stressors but did not differ from younger adults in their exposure to COVID-19 stressors. Additionally, younger adults benefited more from positive events.
Effect of human papilloma virus vaccination on sexual behaviours among adolescent women in Rwanda: a regression discontinuity study
Authors: Hategeka Celestin , Ogilvie Gina , Nisingizwe Marie Paul , Rulisa Stephen , Law Michael R
Published: July 2020

Increasing human papilloma virus (HPV) vaccination coverage is one of the key approaches to preventing cervical cancer globally. However, some argue that HPV vaccine recipients may engage in risky compensatory sexual behaviours because of perceived protection afforded by the vaccine. Therefore, we investigated the impact of a wide-scale HPV vaccination programme on sexual behaviours among adolescent women in Rwanda—the first African country to implement a national HPV vaccination. We identified a cohort of women who were eligible for the HPV vaccination and those who were not eligible from the most recent Rwanda Demographic and Health Survey. We used a quasi-experimental regression discontinuity design, exploiting the quasi-random change in HPV vaccination eligibility in 2011, to compare sexual behaviours among vaccinated and unvaccinated adolescent women. We studied the impact of the vaccination on reported sexual intercourse, average number of sexual partners and teenage pregnancy across the vaccination eligibility threshold. Our analysis included 3052 adolescent women (mean age: 18.6 years), of whom 58% were eligible for HPV vaccination. Nearly one in five adolescents reported having had sexual intercourse (18.5%). The average reported lifetime number of sexual partners was 1.41. The proportion of teenage pregnancy was 5.3%. We found no evidence that HPV vaccination was associated with any significant changes across the eligibility threshold in reported sexual behaviours we studied: no significant increase in the proportion of having sexual intercourse [odds ratio (OR): 0.80, 95% confidence interval (CI): 0.57–1.12; P = 0.19], in lifetime number of sexual partners (rate ratio 0.99, 95% CI: 0.83–1.17, P = 0.91) and in the proportion of teen pregnancies (OR 1.05, 95% CI: 0.50 to 2.20, P = 0.89) at the eligibility threshold. The Rwandan national HPV vaccination programme did not increase sexual behaviours among adolescent women, assuaging concerns of engaging in risky compensatory sexual behaviours some have feared.
Catching up through green windows of opportunity in an era of technological transformation: Empirical evidence from the Chinese wind energy sector
Authors: Dai Yixin , Haakonsson Stine , Oehler Lars
Published: July 2020

Recent transformations in the global wind energy industry have considerable implications for firms to catch up as the sectoral frontier advances from on- and offshore wind turbines towards digital/hybrid systems. These technological shifts potentially precipitate new green windows of opportunity. This article finds that latecomer firms show different capabilities in responding to technological transformation at the global level, which explains variations in catch-up trajectories under the same framework conditions.
Evaluating acoustic-trawl survey strategies using an end-to-end ecosystem model
Authors: Holmin Arne Johannes , Mousing Erik A , Hjøllo Solfrid S , Skogen Morten D , Huse Geir , Handegard Nils Olav
Published: July 2020

Fisheries independent surveys support science and fisheries assessments but are costly. Evaluating the efficacy of a survey before initiating it could save costs. We used the NORWECOM.E2E model to simulate Northeast Atlantic mackerel and Norwegian spring spawning herring distributions in the Norwegian Sea, and we ran vessel transects in silico to simulate acoustic-trawl surveys. The simulated data were processed using standard survey estimation software and compared to the stock abundances in the ecosystem model. Three existing real surveys were manipulated to demonstrate how the simulation framework can be used to investigate effects of changes in survey timing, direction, and coverage on survey estimates. The method picked up general sources of biases and variance, i.e. that surveys conducted during fish migrations are more vulnerable in terms of bias to timing and changes in survey direction than during more stationary situations and that increased effort reduced the sampling variance.
How Concrete Language Shapes Customer Satisfaction
Authors: Packard Grant , Berger Jonah
Published: July 2020

Consumers are often frustrated by customer service. But could a simple shift in language help improve customer satisfaction? We suggest that linguistic concreteness—the tangibility, specificity, or imaginability of words employees use when speaking to customers—can shape consumer attitudes and behaviors. Five studies, including text analysis of over 1,000 real consumer–employee interactions in two different field contexts, demonstrate that customers are more satisfied, willing to purchase, and purchase more when employees speak to them concretely. This occurs because customers infer that employees who use more concrete language are listening (i.e., attending to and understanding their needs). These findings deepen understanding of how language shapes consumer behavior, reveal a psychological mechanism by which concreteness impacts person perception, and provide a straightforward way that managers could help enhance customer satisfaction.
A rare case of duplicated appendix presenting as perforated appendicitis
Authors: Raja A Ashwin , Vasanthakumaran Tamilarasy
Published: July 2020

Anomalies of the appendix have been reported mostly in adults as an incidental finding during surgery. The incidence of duplication of the vermiform appendix is reported to be 0.004% and <10 cases of appendicitis have been reported in duplicated appendix. This is a case report of an 18-year-old male who was diagnosed to have perforated appendicitis by imaging, and on open surgical exploration was found to have appendiceal duplication. Histopathological examination of both specimens revealed a perforated necrotic first appendix and an acutely inflamed second appendix. Surgeons must always bear in mind a high degree of suspicion regarding the possibility of duplicated appendices in all cases that are clinically and radiologically suspected to have acute appendicitis or perforated appendicitis. A thorough intraoperative examination of caecum is mandatory to avoid missing the duplication; thus, preventing post-operative complications and medicolegal issues.
Titanium clip migration after cholecystectomy: original technique for laparoscopic transcystic extraction when endoscopic retrograde cholangiopancreatography fails
Authors: Pantoja Pachajoa Diana A , Bruno Marco A , Doniquian Alejandro M , Alvarez Fernando A
Published: July 2020

Surgical clip migration into the common bile duct (CBD) is a rare complication after laparoscopic cholecystectomy (LC). Few cases of surgical clip migration have been reported in the literature, and most of them have been successfully treated with endoscopic retrograde cholangiopancreatography (ERCP). We present a 71-year-old woman with 48 h of abdominal pain, jaundice and fever 6 years after laparoscopic cholecystectomy. She was diagnosed with common bile duct obstruction from surgical clip migration. After failure of ERCP, the patient was successfully treated with an innovative approach by laparoscopic transcystic extraction using endoscopic hose-type biopsy forceps. The presented technique was feasible and safe in expert hands, representing a valuable alternative to avoid the need of a choledochotomy in patients with unsuccessful ERCP.
Corynebacterium diphtheriae Infection in Mahajanga, Madagascar: First Case Report
Authors: Rakotomalala Rivo Solotiana , Andrianirina Zo Zafitsara , Ratsima Elisoa , Randrianandraina Patrick , Randrianirina Frédérique , Edosoa Glenn Torrencelli , Rabenandrianina Tahirimalala , Badell Edgar , Toubiana Julie , Andrianarimanana Diavolana , Brisse Sylvain , Rasamindrakotroka Andry
Published: July 2020

Diphtheria is an infection that has been unreported for more than two decades in Mahajanga. A child, aged 4, presented with a pseudomembranous pharyngitis was associated with a dysphagia. He was from a rural municipality of Ambato Boeny at Mahajanga province and was admitted to the Pediatric Unit of the University Hospital Center. The child was not immunized against diphtheria. A throat swab was performed and cultured, from which Corynebacterium diphtheriae was identified. The strain, of biovar Mitis, was confirmed as diphtheria toxin (DT)-gene positive and produced DT (Elek test). Unfortunately, the child developed cardiac and neurological complications and died of respiratory and heart failure.
The impact of global selection on local adaptation and reproductive isolation
Authors: Bisschop Gertjan , Setter Derek , Rafajlović Marina , Baird Stuart J. E. , Lohse Konrad
Published: July 2020

Despite the homogenizing effect of strong gene flow between two populations, adaptation under symmetric divergent selection pressures results in partial reproductive isolation: adaptive substitutions act as local barriers to gene flow, and if divergent selection continues unimpeded, this will result in complete reproductive isolation of the two populations, i.e. speciation. However, a key issue in framing the process of speciation as a tension between local adaptation and the homogenizing force of gene flow is that the mutation process is blind to changes in the environment and therefore tends to limit adaptation. Here we investigate how globally beneficial mutations (GBMs) affect divergent local adaptation and reproductive isolation. When phenotypic divergence is finite, we show that the presence of GBMs limits local adaptation, generating a persistent genetic load at the loci that contribute to the trait under divergent selection and reducing genome-wide divergence. Furthermore, we show that while GBMs cannot prohibit the process of continuous differentiation, they induce a substantial delay in the genome-wide shutdown of gene flow.

This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers’.
The limits to parapatric speciation 3: evolution of strong reproductive isolation in presence of gene flow despite limited ecological differentiation
Authors: Blanckaert Alexandre , Bank Claudia , Hermisson Joachim
Published: July 2020

Gene flow tends to impede the accumulation of genetic divergence. Here, we determine the limits for the evolution of postzygotic reproductive isolation in a model of two populations that are connected by gene flow. We consider two selective mechanisms for the creation and maintenance of a genetic barrier: local adaptation leads to divergence among incipient species due to selection against migrants, and Dobzhansky–Muller incompatibilities (DMIs) reinforce the genetic barrier through selection against hybrids. In particular, we are interested in the maximum strength of the barrier under a limited amount of local adaptation, a challenge that many incipient species may initially face. We first confirm that with classical two-locus DMIs, the maximum amount of local adaptation is indeed a limit to the strength of a genetic barrier. However, with three or more loci and cryptic epistasis, this limit holds no longer. In particular, we identify a minimal configuration of three epistatically interacting mutations that is sufficient to confer strong reproductive isolation.

This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers’.
The importance of intrinsic postzygotic barriers throughout the speciation process
Authors: Coughlan Jenn M. , Matute Daniel R.
Published: July 2020

Intrinsic postzygotic barriers can play an important and multifaceted role in speciation, but their contribution is often thought to be reserved to the final stages of the speciation process. Here, we review how intrinsic postzygotic barriers can contribute to speciation, and how this role may change through time. We outline three major contributions of intrinsic postzygotic barriers to speciation. (i)reduction of gene flow: intrinsic postzygotic barriers can effectively reduce gene exchange between sympatric species pairs. We discuss the factors that influence how effective incompatibilities are in limiting gene flow. (ii)early onset of species boundaries via rapid evolution: intrinsic postzygotic barriers can evolve between recently diverged populations or incipient species, thereby influencing speciation relatively early in the process. We discuss why the early origination of incompatibilities is expected under some biological models, and detail how other (and often less obvious) incompatibilities may also serve as important barriers early on in speciation. (iii)reinforcement: intrinsic postzygotic barriers can promote the evolution of subsequent reproductive isolation through processes such as reinforcement, even between relatively recently diverged species pairs. We incorporate classic and recent empirical and theoretical work to explore these three facets of intrinsic postzygotic barriers, and provide our thoughts on recent challenges and areas in the field in which progress can be made.

This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers’.
Can the genomics of ecological speciation be predicted across the divergence continuum from host races to species? A case study inRhagoletis
Authors: Meyers Peter J. , Doellman Meredith M. , Ragland Gregory J. , Hood Glen R. , Egan Scott P. , Powell Thomas H. Q. , Nosil Patrik , Feder Jeffrey L.
Published: July 2020

Studies assessing the predictability of evolution typically focus on short-term adaptation within populations or the repeatability of change among lineages. A missing consideration in speciation research is to determine whether natural selection predictably transforms standing genetic variation within populations into differences between species. Here, we test whether and how host-related selection on diapause timing associates with genome-wide differentiation during ecological speciation by comparing ancestral hawthorn and newly formed apple-infesting host races ofRhagoletis pomonellato their sibling speciesRhagoletis mendaxthat attacks blueberries. The associations of 57 857 single nucleotide polymorphisms in a diapause genome-wide-association study (GWAS) on the hawthorn race strongly predicted the direction and magnitude of genomic divergence among the three fly populations at a field site in Fennville, MI, USA. The apple race andR. mendaxshow parallel changes in the frequencies of putative inversions on three chromosomes associated with the earlier fruiting times of apples and blueberries compared to hawthorns. A diapause GWAS onR. mendaxrevealed compensatory changes throughout the genome accounting for the earlier eclosion of blueberry, but not apple flies. Thus, a degree of predictability, although not complete, exists in the genomics of diapause across the ecological speciation continuum inRhagoletis. The generality of this result is placed in the context of other similar systems.

This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers'.