bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine With an Adenovirus 26 Vector Encoding Prefusion F (Ad26.RSV.preF) in Adults Aged ≥60 Years
Authors: Williams Kristi , Bastian Arangassery Rosemary , Feldman Robert Allen , Omoruyi Edmund , de Paepe Els , Hendriks Jenny , van Zeeburg Hester , Godeaux Olivier , Langedijk Johannes P M , Schuitemaker Hanneke , Sadoff Jerry , Callendret Benoit
Published: April 2020

Background

Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilized in prefusion conformation.

Methods

This phase 1 clinical trial was performed in healthy adults aged ≥60 years. Seventy-two participants received 1 or 2 intramuscular injections of low-dose (LD; 5 × 1010 vector particles) or high-dose (HD; 1 × 1011 vector particles) Ad26.RSV.preF vaccine or placebo, with approximately 12 months between doses and 2-year follow-up for safety and immunogenicity outcomes.

Results

Solicited adverse events were reported by 44% of vaccine recipients and were transient and mild or moderate in intensity. No serious adverse events were related to vaccination. After the first vaccination, geometric mean titers for RSV-A2 neutralization increased from baseline (432 for LD and 512 for HD vaccine) to day 29 (1031 for LD and 1617 for HD). Pre-F–specific antibody geometric mean titers and median frequencies of F-specific interferon γ–secreting T cells also increased substantially from baseline. These immune responses were still maintained above baseline levels 2 years after immunization and could be boosted with a second immunization at 1 year.

Conclusions

Ad26.RSV.preF (LD and HD) had an acceptable safety profile and elicited sustained humoral and cellular immune responses after a single immunization in older adults.
The Stringent Response Contributes to Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection Through the Purine Biosynthetic Pathway
Authors: Li Liang , Bayer Arnold S , Cheung Ambrose , Lu Lou , Abdelhady Wessam , Donegan Niles P , Hong Jong-In , Yeaman Michael R , Xiong Yan Q
Published: April 2020

Persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections represent a significant clinical-therapeutic challenge. Of particular concern is antibiotic treatment failure in infections caused by MRSA that are “susceptible” to antibiotic in vitro. In the current study, we investigate specific purine biosynthetic pathways and stringent response mechanism(s) related to this life-threatening syndrome using genetic matched persistent and resolving MRSA clinical bacteremia isolates (PB and RB, respectively), and isogenic MRSA strain sets. We demonstrate that PB isolates (vs RB isolates) have significantly higher (p)ppGpp production, phenol-soluble-modulin expression, polymorphonuclear leukocyte lysis and survival, fibronectin/endothelial cell (EC) adherence, and EC damage. Importantly, an isogenic strain set, including JE2 parental, relP-mutant and relP-complemented strains, translated the above findings into significant outcome differences in an experimental endocarditis model. These observations indicate a significant regulation of purine biosynthesis on stringent response, and suggest the existence of a previously unknown adaptive genetic mechanism in persistent MRSA infection.
Subordinate-State Agency and US Hegemony: Colombian Consent versus Bolivian Dissent
Authors: Kat Quintijn B
Published: April 2020

The strategies of subordinate states in hegemonic or asymmetrical relations have been widely studied by international relations scholars. Such works generally focus on how a subordinate state can influence the hegemon's behavior so as to address and further the interests of the subordinate state. The relation between subordinate-state agency and the hegemonic system, the makeup of the hegemonic order, itself receives less attention. Through analysis of two cases of US hegemony in Latin America, this article examines how subordinate-state agency may strengthen or weaken the hegemonic system and, as such, makes a case for subordinate-state agency as an underpinning element of hegemony. It explores Colombian agency in the design phase of Plan Colombia as contributing to US hegemony, while Bolivian agency under the presidency of Evo Morales is examined as a challenge. In both instances, it was the United States, rather than the Latin American states, that took on a passive role, leaving the initiative with Colombia and Bolivia. Therefore, instead of reaffirmations of active one-way US hegemony versus passive subordinate states, the paper proposes to understand both cases as demonstrating the importance of subordinate-state agency in the configuration of the hegemonic system.
Comparison of LC-MS/MS and Enzymatic Methods for the Determination of Total Choline and Total Carnitine in Infant Formula and Milk Products
Authors: Gill Brendon D , Indyk Harvey E , Kobayashi Tadashi , McGrail Iain J , Woollard David C
Published: April 2020

Background

Choline and l-carnitine are classified as pseudo-vitamins because of their conditionally essential status. As they are involved in multiple physiological metabolic pathways in the human body, they are routinely fortified in infant and adult nutritional formulas.

Objective

The performance of an LC-MS/MS method for the analysis of choline and carnitine, compared with enzymatic methods in routine use for the analysis of total carnitine and total choline, is described.

Method

Powder samples were reconstituted, with release of carnitine and choline facilitated by both acid and alkaline hydrolysis and the extract analyzed by LC-MS/MS. Quantitation was by internal standard technique using deuterium-labeled carnitine and deuterium-labeled choline.

Results

Method range, specificity, sensitivity, precision, recovery, accuracy, and ruggedness were assessed for milk powders, infant formulas, and soy- and milk-based nutritional products. Spike recoveries of 94.0–108.4% were obtained for both total carnitine and choline, and no statistical bias (α = 0.05) between measured results and certified values (choline: P = 0.36; free carnitine: P = 0.67) was found for NIST 1849a certified reference material (NIST1849a). Precision, as repeatability relative standard deviation (RSD), was 2.0% RSDr for total carnitine and 1.7% RSDr for total choline. Equivalent results for total choline and total carnitine were obtained by LC-MS/MS and enzymatic methods (n = 30).

Conclusions

The described LC-MS/MS method is fit for purpose for routine product compliance release testing environments. This validation study has confirmed that alternative enzymatic assays can be used with confidence in laboratories in which LC-MS/MS platforms are unavailable.

Highlights

An LC-MS/MS method was evaluated and found to be fit-for-purpose for routine product compliance release testing of infant formula. The LC-MS/MS method was compared with enzymatic methods for the analysis of total carnitine and total choline. Alternative enzymatic assays can be used with confidence in laboratories in which LC-MS/MS platforms are unavailable.
Formaldehyde Reacts with Amino Acids and Peptides with a Potential Role in Acute Methanol Intoxication
Authors: Sýkora David , Jindřich Jindřich , Král Vladimír , Jakubek Milan , Tatar Ameneh , Kejík Zdeněk , Martásek Pavel , Zakharov Sergey
Published: April 2020

Methanol, an aliphatic alcohol widely used in the industry, causes acute and chronic intoxications associated with severe long-term health damage, including permanent visual impairment, brain damage, mainly necrosis of the basal ganglia and high mortality due to cancer. However, the role of formaldehyde, an intermediate metabolite of methanol oxidation, in methanol toxicity remains unclear. Thus, we studied the reactivity of several amino acids and peptides in the presence of formaldehyde by identifying products by direct infusion electrospray high-resolution mass spectrometry (MS) and matrix-assisted laser desorption-ionization MS. Cysteine, homocysteine and two peptides, CG and CGAG, provided cyclic products with a +12 amu mass shift with respect to the original compounds. The proposed structures of the products were confirmed by high-resolution tandem MS. Moreover, the formation of the products with +12 amu mass shift was also shown for two biologically relevant peptides, fragments of ipilimumab, which is a human IgG1 monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4. Overall, our experimental results indicate that formaldehyde reacts with some amino acids and peptides, yielding covalently modified structures. Such chemical modifications may induce undesirable changes in the properties and function of vital biomolecules (e.g., hormones, enzymes) and consequently pathogenesis.
The Exceptional Responders Initiative: Feasibility of a National Cancer Institute Pilot Study
Authors: Conley Barbara A , Staudt Lou , Takebe Naoko , Wheeler David A , Wang Linghua , Cardenas Maria F , Korchina Viktoriya , Zenklusen Jean Claude , McShane Lisa M , Tricoli James V , Williams Paul M , Lubensky Irina , O’Sullivan-Coyne Geraldine , Kohn Elise , Little Richard F , White Jeffrey , Malik Shakun , Harris Lyndsay N , Mann Bhupinder , Weil Carol , Tarnuzzer Roy , Karlovich Chris , Rodgers Brian , Shankar Lalitha , Jacobs Paula M , Nolan Tracy , Berryman Sean M , Gastier-Foster Julie , Bowen Jay , Leraas Kristen , Shen Hui , Laird Peter W , Esteller Manel , Miller Vincent , Johnson Adrienne , Edmondson Elijah F , Giordano Thomas J , Kim Benjamin , Ivy S Percy
Published: April 2020

Background

Tumor molecular profiling from patients experiencing exceptional responses to systemic therapy may provide insights into cancer biology and improve treatment tailoring. This pilot study evaluates the feasibility of identifying exceptional responders retrospectively, obtaining pre-exceptional response treatment tumor tissues, and analyzing them with state-of-the-art molecular analysis tools to identify potential molecular explanations for responses.

Methods

Exceptional response was defined as partial (PR) or complete (CR) response to a systemic treatment with population PR or CR rate less than 10% or an unusually long response (eg, duration >3 times published median). Cases proposed by patients’ clinicians were reviewed by clinical and translational experts. Tumor and normal tissue (if possible) were profiled with whole exome sequencing and, if possible, targeted deep sequencing, RNA sequencing, methylation arrays, and immunohistochemistry. Potential germline mutations were tracked for relevance to disease.

Results

Cases reflected a variety of tumors and standard and investigational treatments. Of 520 cases, 476 (91.5%) were accepted for further review, and 222 of 476 (46.6%) proposed cases met requirements as exceptional responders. Clinical data were obtained from 168 of 222 cases (75.7%). Tumor was provided from 130 of 168 cases (77.4%). Of 117 of the 130 (90.0%) cases with sufficient nucleic acids, 109 (93.2%) were successfully analyzed; 6 patients had potentially actionable germline mutations.

Conclusion

Exceptional responses occur with standard and investigational treatment. Retrospective identification of exceptional responders, accessioning, and sequencing of pretreatment archived tissue is feasible. Data from molecular analyses of tumors, particularly when combining results from patients who received similar treatments, may elucidate molecular bases for exceptional responses.
Unexpected Cholera Bacteremia in a 91 Year Old Caucasian Male Patient
Authors: Thwe Phyu M , Schilling Matthew , Reynoso David , Ren Ping
Published: April 2020

Cholera is an illness caused by Vibrio cholerae; its main symptom is acute watery diarrhea. Some infections are asymptomatic or result in patients presenting with mild diarrhea, but complications, such as bacteremia, can be fatal. Being endemic in Africa, Southeast Asia, and Haiti, V. cholerae infection cases in the United States are primarily considered travel-related. Herein, we report a case of a 91 year old Caucasian man, a Texas Gulf Coast resident, who developed bacteremia due to V. cholerae despite having no international travel history. Culture workup by mass spectrometry, automated biochemical system, and 16S ribosomal RNA (rRNA) gene sequencing confirmed V. cholerae. This case conveys an important reminder to clinicians and laboratory professionals regarding potentially serious cholera illnesses due to the domestic prevalence of V. cholerae in the coastal regions of the United States.
Case Report: Buprenorphine Induction Using Transdermal Buprenorphine in a Veteran With Opioid Use Disorder and Psychosis, Managing Precipitated Withdrawal
Authors: Kinasz Kathryn R , Herbst Ellen D , Kalapatapu Raj K
Published: April 2020

Buprenorphine induction can lead to precipitated opioid withdrawal, even when using novel techniques such as transdermal buprenorphine. Involuntary limb movements are a distressing symptom of precipitated withdrawal that can be difficult to treat. We report a case of a military veteran transitioning from methadone to buprenorphine for the treatment of opioid use disorder (OUD) using small doses of transdermal buprenorphine. Herein, we review the literature associated with opioid withdrawal-related restlessness. Despite the known risk of concurrent benzodiazepine and buprenorphine administration, including decreased respiratory rate and death, we present a clinical presentation in which this medication combination may be necessary while under medical supervision. We suggest a stepwise algorithm for pharmacotherapy in patients experiencing involuntary limb movements associated with precipitated withdrawal. To safeguard the success of medication-assisted treatment (MAT) for opioid addiction, clinicians should be aware of potential clinical challenges when managing precipitated opioid withdrawal in patients with complex psychiatric comorbidities.
The History of Swedish Military Healthcare System and Its Path Toward Civilian-Military Collaboration From a Total Defense Perspective
Authors: Khorram-Manesh Amir , Robinson Yohan , Boffard Ken , Örtenwall Per
Published: April 2020

Introduction

The interaction between military and civilian healthcare systems has contributed to the development of medical care. Swedish innovations such as the Seldinger technique for angiography, Leksell Gamma Knife for cranial surgery, and the introduction of pacemakers and ultrasound have contributed to the global development of medicine. Several authors have described the Swedish civilian healthcare system and its development. However, the development and history of its military healthcare system and its influence on the civilian healthcare system remain untold. This review aims to describe the historical development of the Swedish military healthcare system and its path toward civilian-military collaboration and a total defense healthcare system.

Material and Methods

A search for all published scientific papers in Swedish and English, along with available legal documents and directives, was made. We used CINAHL, PubMed, Scopus, and Gothenburg University’s databases and search engines. The following keywords, Swedish, military, civilian, healthcare, collaboration, and development, were searched for, alone or in combination, using a PRISMA flow chart. Duplicates, abstracts, and nonscientific publications were excluded.

Results

Each of the four distinct periods of historical development in the Swedish military healthcare system can be characterized by the changes necessary for transforming Sweden from an aggressive to a defensive and collaborative nation, with national and international engagement. Collaboration not only encompasses readiness and willingness to share resources and information, and to adjust routines and guidelines, but also needs a culture of consensus and respect for each other’s limitations and capabilities. The definition of military medicine and the military physician’s role in Sweden is imperative for further civilian-military collaboration.

Conclusions

Recent global sociopolitical changes necessitate civilian-military healthcare collaboration. Although civilian-military healthcare partnerships in various medical fields have been reported earlier, the Swedish concept of total defense’s healthcare system integration and collaboration may be a more fruitful approach. The collaboration within the total defense healthcare system will result in technical achievements, innovations, and medical advancements for the benefit of the whole nation.
Colour–colour and colour–magnitude diagrams for hot Jupiters
Authors: Melville G , Kedziora-Chudczer L , Bailey J
Published: April 2020

We use ground-based and space-based eclipse measurements for the near-infrared (IR) bands (JHKs) and Spitzer 3.6- and 4.5-μm bands to construct colour–colour and colour–magnitude diagrams for hot Jupiters. We compare the results with previous observations of substellar objects and find that hot Jupiters, when corrected for their inflated radii, lie near the blackbody line and in the same region of the colour–magnitude diagrams as brown dwarfs, including low-gravity dwarfs that have been previously suggested as exoplanet analogues. We use theoretical emission spectra to investigate the effects of different metallicity, C/O ratios, and temperatures on the IR colours. In general, we find that while differences in C/O ratio and metallicity do correspond to different locations on these diagrams, the measurement errors are too large to use this method to put strong constraints on the composition of individual objects. However, as a class, hot Jupiters cluster around the location expected for solar metallicity and C/O ratio.
The flatness problem and the age of the Universe
Authors: Helbig Phillip
Published: April 2020

Several authors have made claims, none of which has been rebutted, that the flatness problem, as formulated by Dicke and Peebles, is not really a problem but rather a misunderstanding. Nevertheless, the flatness problem is still widely perceived to be real. Most of the arguments against the idea of a flatness problem are based on the change with time of the density parameter Ω and normalized cosmological constant λ and, since the Hubble constant H is not considered, are independent of time-scale. An independent claim is that fine-tuning is required in order to produce a Universe which neither collapsed after a short time nor expanded so quickly that no structure formation could take place. I show that this claim does not imply that fine-tuning of the basic cosmological parameters is necessary, in part for similar reasons as in the more restricted flatness problem and in part due to an incorrect application of the idea of perturbing the early Universe in a gedankenexperiment; I discuss some typical pitfalls of the latter.
The CO-dark molecular gas mass in 30 Doradus
Authors: Chevance Mélanie , Madden Suzanne C , Fischer Christian , Vacca William D , Lebouteiller Vianney , Fadda Dario , Galliano Frédéric , Indebetouw Remy , Kruijssen J M Diederik , Lee Min-Young , Poglitsch Albrecht , Polles Fiorella L , Cormier Diane , Hony Sacha , Iserlohe Christof , Krabbe Alfred , Meixner Margaret , Sabbi Elena , Zinnecker Hans
Published: April 2020

Determining the efficiency with which gas is converted into stars in galaxies requires an accurate determination of the total reservoir of molecular gas mass. However, despite being the most abundant molecule in the Universe, H2 is challenging to detect through direct observations and indirect methods have to be used to estimate the total molecular gas reservoir. These are often based on scaling relations from tracers such as CO or dust, and are generally calibrated in the Milky Way. Yet, evidence that these scaling relations are environmentally dependent is growing. In particular, the commonly used CO-to-H2 conversion factor (XCO) is expected to be higher in metal-poor and/or strongly UV-irradiated environments. We use new SOFIA/FIFI-LS observations of far-infrared fine-structure lines from the ionized and neutral gas and the Meudon photodissociation region model to constrain the physical properties and the structure of the gas in the massive star-forming region of 30 Doradus in the Large Magellanic Cloud, and determine the spatially resolved distribution of the total reservoir of molecular gas in the proximity of the young massive cluster R136. We compare this value with the molecular gas mass inferred from ground-based CO observations and dust-based estimates to quantify the impact of this extreme environment on commonly used tracers of the molecular gas. We find that the strong radiation field combined with the half-solar metallicity of the surrounding gas is responsible for a large reservoir of ‘CO-dark’ molecular gas, leaving a large fraction of the total H2 gas (≳75 per cent) undetected when adopting a standard XCO factor in this massive star-forming region.
The closest extremely low-mass white dwarf to the Sun
Authors: Kawka Adela , Simpson Jeffrey D , Vennes Stéphane , Bessell Michael S , Da Costa Gary S , Marino Anna F , Murphy Simon J
Published: April 2020

We present the orbit and properties of 2MASS J050051.85−093054.9, establishing it as the closest (d ≈ 71 pc) extremely low-mass white dwarf to the Sun. We find that this star is hydrogen rich with $T_\textrm {eff}\approx 10\, 500$ K, log g ≈ 5.9, and, following evolutionary models, has a mass of ≈0.17 M⊙. Independent analysis of radial velocity and Transiting Exoplanet Survey Satellite(TESS) photometric time series reveals an orbital period of ≈9.5 h. Its high velocity amplitude ($K\approx 144~\textrm {km}\, \textrm {s}^{-1}$) produces a measurable Doppler beaming effect in the TESSlight curve with an amplitude of 1 mmag. The unseen companion is most likely a faint white dwarf. J0500−0930 belongs to a class of post-common envelope systems that will most likely merge through unstable mass transfer and in specific circumstances lead to Type Ia supernova explosions.
H2B ubiquitylation enhances H3K4 methylation activities of human KMT2 family complexes
Authors: Kwon Minjung , Park Kihyun , Hyun Kwangbeom , Lee Jeong-Heon , Zhou Linjiao , Cho Young-Wook , Ge Kai , Skalnik David G , Muir Tom W , Kim Jaehoon
Published: April 2020

In mammalian cells, distinct H3K4 methylation states are created by deposition of methyl groups by multiple complexes of histone lysine methyltransferase 2 (KMT2) family proteins. For comprehensive analyses that directly compare the catalytic properties of all six human KMT2 complexes, we employed a biochemically defined system reconstituted with recombinant KMT2 core complexes (KMT2CoreCs) containing minimal components required for nucleosomal H3K4 methylation activity. We found that each KMT2CoreC generates distinct states and different levels of H3K4 methylation, and except for MLL3 all are stimulated by H2Bub. Notably, SET1BCoreC exhibited the strongest H3K4 methylation activity and, to our surprise, did not require H2B ubiquitylation (H2Bub); in contrast, H2Bub was required for the H3K4me2/3 activity of the paralog SET1ACoreC. We also found that WDR5, RbBP5, ASH2L and DPY30 are required for efficient H3K4 methyltransferase activities of all KMT2CoreCs except MLL3, which could produce H3K4me1 in the absence of WDR5. Importantly, deletion of the PHD2 domain of CFP1 led to complete loss of the H3K4me2/3 activities of SET1A/BCoreCs in the presence of H2Bub, indicating a critical role for this domain in the H2Bub-stimulated H3K4 methylation. Collectively, our results suggest that each KMT2 complex methylates H3K4 through distinct mechanisms in which individual subunits differentially participate.
Emergence of a novel immune-evasion strategy from an ancestral protein fold in bacteriophage Mu
Authors: Karambelkar Shweta , Udupa Shubha , Gowthami Vykuntham Naga , Ramachandra Sharmila Giliyaru , Swapna Ganduri , Nagaraja Valakunja
Published: April 2020

The broad host range bacteriophage Mu employs a novel ‘methylcarbamoyl’ modification to protect its DNA from diverse restriction systems of its hosts. The DNA modification is catalyzed by a phage-encoded protein Mom, whose mechanism of action is a mystery. Here, we characterized the co-factor and metal-binding properties of Mom and provide a molecular mechanism to explain ‘methylcarbamoyl’ation of DNA by Mom. Computational analyses revealed a conserved GNAT (GCN5-related N-acetyltransferase) fold in Mom. We demonstrate that Mom binds to acetyl CoA and identify the active site. We discovered that Mom is an iron-binding protein, with loss of Fe2+/3+-binding associated with loss of DNA modification activity. The importance of Fe2+/3+ is highlighted by the colocalization of Fe2+/3+ with acetyl CoA within the Mom active site. Puzzlingly, acid-base mechanisms employed by >309,000 GNAT members identified so far, fail to support methylcarbamoylation of adenine using acetyl CoA. In contrast, free-radical chemistry catalyzed by transition metals like Fe2+/3+ can explain the seemingly challenging reaction, accomplished by collaboration between acetyl CoA and Fe2+/3+. Thus, binding to Fe2+/3+, a small but unprecedented step in the evolution of Mom, allows a giant chemical leap from ordinary acetylation to a novel methylcarbamoylation function, while conserving the overall protein architecture.
The efficacy and safety of roxadustat for anemia in patients with chronic kidney disease: a meta-analysis
Authors: Zheng Qiyan , Yang Huisheng , Fu Xinwen , Huang Yishan , Wei Ruojun , Wang Yahui , Liu Yu Ning , Liu Wei Jing
Published: April 2020

Background

Chronic kidney disease (CKD) is an increasing public health issue. Anemia, which is a complication of CKD, is associated with reduced quality of life and increased morbidity and mortality. Currently quite a few clinical studies have been conducted to compare roxadustat with epoetin alfa [all for dialysis-dependent (DD) patients] or placebo [all for nondialysis-dependent (NDD) patients]. Our meta-analysis aimed to investigate the efficacy and safety of roxadustat for anemia in patients with CKD.

Methods

We thoroughly searched eight electronic resource databases for randomized controlled trials (RCTs) comparing the efficacy and safety between roxadustat versus epoetin alfa or placebo for the treatment of anemia in patients with CKD.

Results

Four Phase 2 and two Phase 3 studies with 1010 participants were included. Hemoglobin (Hb) and transferrin levels were increased significantly in the roxadustat group versus those in the placebo {standard mean difference [SMD] 1.57 [95% confidence interval (CI) 1.17–1.98]; SMD 1.81 [95% CI 1.53–2.08]; respectively, both low-quality evidence} or epoetin alfa group [SMD 0.47 (95% CI 0.02–0.93), very low-quality evidence; SMD 1.05 (95% CI 0.81–1.29), low-quality evidence; respectively]. Hepcidin levels were reduced significantly in the roxadustat group versus those in the placebo [SMD −1.72 (95% CI −3.03 to −0.41), very low-quality evidence] or epoetin alfa group [SMD −0.23 (95% CI −0.43 to −0.02), low-quality evidence]. Ferritin and serum transferrin saturation (TSAT) levels were reduced significantly in the roxadustat group versus those in the placebo group [SMD −0.82 (95% CI −1.31 to −0.33); SMD −0.54 (95% CI −0.76 to −0.32), respectively; both low-quality evidence] and ferritin and TSAT levels in the roxadustat group were comparable to those in the epoetin alfa group [SMD 0.02 (95% CI −0.18–0.21); SMD 0.15 (95% CI −0.04–0.35), respectively, both low-quality evidence]. As for safety, the incidence of adverse events (AEs) in the roxadustat group was insignificantly different from that of the placebo group [risk ratio (RR) 0.99 (95% CI 0.83–1.18); P = 0.89, very low-quality evidence]. But the incidence of AEs in the roxadustat group was significantly higher than that in the epoetin alfa group [RR 1.25 (95% CI 1.01–1.54); P = 0.04, low-quality evidence]. There was no significant association between roxadustat and the incidence of serious AEs (SAEs) for both NDD and DD patients [RR 1.08 (95% CI 0.51–2.28) and RR 1.43 (95% CI 0.85–2.40), respectively, both very low-quality evidence].

Conclusion

In this meta-analysis of RCTs, we found evidence that after the oral administration of roxadustat, NDD patients’ Hb levels were increased effectively and DD patients’ Hb levels were maintained effectively. The risk of SAEs was not observed with the short-term use of roxadustat. These findings support roxadustat for the treatment of anemia in patients with CKD.
Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic
Authors: Anders Hans-Joachim , Bruchfeld Annette , Fernandez Juarez Gema Maria , Floege Jürgen , Goumenos Dimitrios , Turkmen Kultigin , van Kooten Cees , Tesar Vladimir , Segelmark Mårten
Published: April 2020

The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.
Sleep disturbances among medical workers during the outbreak of COVID-2019
Authors: Wang S , Xie L , Xu Y , Yu S , Yao B , Xiang D
Published: April 2020

Background

The outbreak of Corona Virus Disease-2019 (COVID-19) has posed unprecedented pressure and threats to healthcare workers in Wuhan and the entire country.

Aims

To assess the effect of the COVID-19 outbreak on the sleep quality of healthcare workers in a children’s healthcare centre in Wuhan.

Methods

A cross-sectional, anonymized, self-reported questionnaire survey was conducted at the Children’s Healthcare Centre of Renmin Hospital, Wuhan University, Wuhan, China. The questionnaire consisted of three parts, including socio-demographic characteristics and COVID-19 epidemic-related factors, the Pittsburgh sleep quality index (PSQI), and Zung’s self-rating anxiety scale (SAS) and self-rating depression scale (SDS).

Results

In total, 47 out of 123 (38%) participants with PSQI scores > 7 were identified as having sleep disturbance. A logistic regression analysis showed that sleep disturbance was independently associated with being an only child (adjusted odds ratio (OR) and 95% confidence interval (CI) 3.40 (1.21–9.57), P < 0.05), exposure to COVID-19 patients (adjusted OR and 95% CI 2.97 (1.08–8.18), P < 0.05) and depression (adjusted OR and 95% CI 2.83 (1.10–7.27), P < 0.05).

Conclusions

We observed that, during the outbreak of COVID-19, sleep disturbance was highly prevalent among paediatric healthcare workers, and sleep disturbance was independently associated with being an only child, exposure to COVID-19 patients and depression. Therefore, more mental health services are required for front-line paediatric healthcare workers in Wuhan.
Sero-evaluation of Immune Responses to Vibrio cholerae in a Postelimination Setting
Authors: Diep Tai The , Jensen Owen , Van Thuong Nguyen , Nhi Nguyen Thi Ngoc , Thu Nguyen Ngoc Anh , Quang Vo Ngoc , Hieu Truong Cong , Thang Hoang Anh , Thuy Nguyen Dieu , Thang Ho Vinh , Tuyen Ho Trung , Ngan Le Dang , Ha Nguyen Thi Thanh , Dung Than Duc , Anderson Cole P , Azman Andrew S , Leung Daniel T
Published: April 2020

Cholera remains a significant public health problem worldwide. In settings of declining incidence, serosurveillance may be used to augment clinical surveillance. We utilized dried blood spot sampling and cholera-specific antibody testing to examine the serologic profiles of vaccinated and unvaccinated children in southern Vietnam, where cholera was recently eliminated.
Practicing Antimicrobial Stewardship: De-Escalating Antibiotics in Patients With Acute Myeloid Leukemia and Neutropenic Fever
Authors: Fuller Risa , Moshier Erin , Jacobs Samantha E , Tremblay Douglas , Lancman Guido , Coltoff Alexander , Caro Jessica , Mascarenhas John , Rana Meenakshi
Published: April 2020

We compared risk of recurrent fever in patients with acute myeloid leukemia undergoing induction chemotherapy with febrile neutropenia without an infectious source in which antibacterials were de-escalated before neutrophil recovery versus continued. There was less recurrent fever when antibacterials were de-escalated early with no increased adverse events.
Discovery of radio jets in the Phoenix galaxy cluster center
Authors: Akahori Takuya , Kitayama Tetsu , Ueda Shutaro , Izumi Takuma , Lee Kianhong , Kawabe Ryohei , Kohno Kotaro , Oguri Masamune , Takizawa Motokazu
Published: April 2020

We report the results of the Australia Telescope Compact Array (ATCA) 15 mm observation of the Phoenix galaxy cluster possessing an extreme star-burst brightest cluster galaxy (BCG) at the cluster center. We spatially resolved radio emission around the BCG, and found diffuse bipolar and bar-shape structures extending from the active galactic nucleus (AGN) of the BCG. They are likely radio jets/lobes, whose sizes are ∼10–20 kpc and locations are aligned with X-ray cavities. If we assume that the radio jets/lobes expand with the sound velocity, their ages are estimated to be ∼10 Myr. We also found compact radio emissions near the center and suggest that they are more young bipolar jets ∼1 Myr in age. Moreover, we found extended radio emission surrounding the AGN and discussed the possibility that the component is a product of the cooling flow, by considering synchrotron radiation partially absorbed by molecular clumps, free–free emission from the warm ionized gas, and the spinning dust emission from the dusty circumgalactic medium.
86-GHz SiO masers in Galactic centre OH/IR stars
Authors: Messineo Maria , Sjouwerman Lorant O , Habing Harm J , Omont Alain
Published: April 2020

We present results on a search for 86.243-GHz SiO (J = 2→1, $v$ = 1) maser emission toward 67 OH/IR stars located near the Galactic centre. We detected 32 spectral peaks, of which 28 correspond to SiO maser lines arising from the envelopes of these OH/IR stars. In OH/IR stars, we obtained an SiO maser detection rate of about $40\%$. We serendipitously detected two other lines from OH/IR stars at ≈86.18 GHz, which could be due to a CCS-molecule transition at 86.181 GHz or probably to an highly excited OH molecular transition at 86.178 GHz. The detection rate of 86-GHz maser emission is found to be about $60\%$ for sources with the Midcourse Space Experiment (MSX) A − E < 2.5 mag; but it drops to $25\%$ for the reddest OH/IR stars with MSX A − E > 2.5 mag. This supports the hypothesis by Messineo (2002, A&A, 393, 115) that the SiO masers are primarily found in relatively thinner circumstellar material.
Drought tolerance and acclimation in Pinus ponderosa seedlings: the influence of nitrogen form
Authors: Sigala José A , Uscola Mercedes , Oliet Juan A , Jacobs Douglass F
Published: April 2020

Drought is a limiting factor to forest regeneration and restoration, which is likely to increase in intensity and duration under future climates. Nitrogen (N) nutrition is related to drought-resistance mechanisms in trees. However, the influence of chemical N form (inorganic and organic N) on physiological traits related to drought resistance has been sparsely studied in conifer seedlings. We investigated the effect of N forms on morpho-physiological traits of Pinus ponderosa Dougl. ex Laws. seedlings and subsequent influences in drought tolerance and acclimation. One-year-old seedlings were fertilized during 10 weeks at 9 mM N with different N forms [either NH4+, NO3− or organic N (amino acids mixture)] in their second year of growth. After fertilization, we measured traits associated with intrinsic drought tolerance (shoot water relations, osmotic regulation, photosynthesis and cell membrane stability). Seedlings were then subjected to an 8-week drought period at varying drought intensities to evaluate plant acclimation mechanisms. We demonstrated that P. ponderosa seedlings could efficiently use amino acids as a primary N source, showing similar performance to those grown with inorganic N forms. Nitrogen form influenced mainly drought-acclimation mechanisms rather than intrinsic drought tolerance. Osmotic potential at saturation (Ψπsat) was marginally affected by N form, and a significant relationship between proline concentration in needles and Ψπsat was found. During acclimation, seedlings fertilized with organic N minimized needle senescence, retained more nutrients in the oldest needles, had maximum increments in proline concentration and hastened the development of water-use efficiency mechanisms compared with those fertilized with inorganic N sources. Our results suggest an improved physiological drought acclimation of organic N-fertilized seedlings.
The acid invertase gene family is involved in internode elongation in Phyllostachys heterocycla cv. pubescens
Authors: Guo Xiaoqin , Chen Hongjun , Liu Yue , Chen Wei , Ying Yeqing , Han Junjie , Gui Renyi , Zhang Hongxia
Published: April 2020

Acid invertases (INVs) play a pivotal role in both vegetative and reproductive growth of plants. However, their possible functions in fast-growing plants such as bamboo are largely unknown. Here, we report the molecular characterization of acid INVs in Phyllostachys heterocycla cv. pubescens, a fast-growing bamboo species commercially grown worldwide. Nine acid INVs (PhINVs), including seven cell wall INVs (PhCWINV1, PhCWINV2, PhCWINV3, PhCWINV4, PhCWINV5, PhCWINV6 and PhCWINV7) and two vacuolar INVs (PhVINV11 and PhVINV12) were isolated. Bioinformatic analyses demonstrated that they all share high amino acid identity with other INVs from different plant species and contain the motifs typically conserved in acid INV. Enzyme activity assays revealed a significantly higher INV activity in the fast-growing tissues, such as the elongating internodes of stems. Detailed quantitative reverse-transcription PCR analyses showed various expression patterns of PhINVs at different developmental stages of the elongating stems. With the exception of PhCWINV6, all PhINVs were ubiquitously expressed in a developmental-specific manner. Further studies in Arabidopsis exhibited that constitutive expression of PhCWINV1, PhCWINV4 or PhCWINV7 increased the biomass production of transgenic plants, as indicated by augmented plant heights and shoot dry weights than the wild-type plants. All these results suggest that acid INVs play a crucial role in the internode elongation of P. heterocycla cv. pubescens and would provide valuable information for the dissection of their exact biological functions in the fast growth of bamboo.
Endophytic Colonization of Rice (Oryza sativa L.) by the Symbiotic Strain Nostoc punctiforme PCC 73102
Authors: Álvarez Consolación , Navarro José A. , Molina-Heredia Fernando P. , Mariscal Vicente
Published: April 2020

Cyanobacteria are phototrophic microorganisms able to establish nitrogen-fixing symbiotic associations with representatives of all four of the major phylogenetic divisions of terrestrial plants. Despite increasing knowledge on the beneficial effects of cyanobacteria in rice fields, the information about the interaction between these microorganisms and rice at the molecular and structural levels is still limited. We have used the model nitrogen-fixing cyanobacterium Nostoc punctiforme to promote a long-term stable endophytic association with rice. Inoculation with this strain of hydroponic cultures of rice produces a fast adherence of the cyanobacterium to rice roots. At longer times, cyanobacterial growth in the proximity of the roots increased until reaching a plateau. This latter phase coincides with the intracellular colonization of the root epidermis and exodermis. Structural analysis of the roots revealed that the cyanobacterium use an apoplastic route to colonize the plant cells. Moreover, plant roots inoculated with N. punctiforme show both the presence of heterocysts and nitrogenase activity, resulting in the promotion of plant growth under nitrogen deficiency, thus providing benefits for the plant.
Overexpression of Strigolactone-Associated Genes Exerts Fine-Tuning Selection on Soybean Rhizosphere Bacterial and Fungal Microbiome
Authors: Liu Fang , Rice John Hollis , Lopes Valeria , Grewal Parwinder , Lebeis Sarah L. , Hewezi Tarek , Staton Margaret E.
Published: April 2020

Strigolactones are a recently discovered class of carotenoid-derived plant hormones with a wide variety of functions, including acting as signaling molecules in the rhizosphere to promote arbuscular mycorrhizal fungi colonization and parasitic seed germination. To determine whether strigolactones influence the recruitment of microbes to the rhizosphere, we characterized both bacterial and fungal communities in response to the overexpression of genes involved in strigolactone biosynthesis (MAX1d) and signaling perception (D14 and MAX2a) in soybean (Glycine max). The amplicon sequencing-based results suggest that strigolactone overexpression lines had altered soybean rhizosphere bacteria composition at both the community level and individual taxa level with genera including Shinella and Bdellovibrio consistently more abundant across all three overexpression constructs. In addition, the responses of the soybean rhizosphere bacteria community differed significantly across the genes, with lines overexpressing genes involved in strigolactone biosynthesis (MAX1d) yielding a divergent bacterial community in comparison with those with altered expression of strigolactone perception genes (D14 and MAX2a). The overexpressed genes did not significantly impact the overall fungal community distribution; however, some individual taxa were altered in abundance. MAX1d and D14 overexpression lines had significantly enriched abundance of Fusarium solani. The mediating role of strigolactone biosynthesis and signaling genes on soybean rhizosphere bacterial and fungal communities confirmed strigolactone’s importance in the rhizosphere host–microbe communication and microbial community structure.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Identification, Pathogenicity, and Fungicide Sensitivity of Ascochyta caulina (Teleomorph: Neocamarosporium calvescens) Associated with Black Stem on Quinoa in China
Authors: Yin Hui , Zhou Jianbo , Lv Hong , Qin Nan , Chang Fang Juan , Zhao Xiaojun
Published: April 2020

Quinoa black stem is a new disease that affects the stems of quinoa plants and is more likely to develop under cool conditions (15 to 25°C, RH = 55 ± 2%). The typical symptoms include the formation of black necrotic lesions on the stem, which can completely wrap around the stem, causing lodging and blanking (development of ‘empty’ and sterile grain on the panicle). Furthermore, the pycnidia form small round protrusions on the surface of the lesions. Phylogenetic analysis revealed that representative isolates LMHS-3 and LMHS-5 were closely related to Ascochyta caulina (teleomorph: Neocamarosporium calvescens). Comprehensive morphological and molecular characterizations confirmed A. caulina as the pathogen that caused quinoa black stem. A. caulina mainly infected quinoa stems and could produce many pycnidia, but it rarely infected quinoa leaves. Pathogenicity testing showed that the most suitable temperature for the onset of quinoa black stem was from 15 to 25°C. When the temperature was increased above 30°C, the conidial germination of A. caulina became malformed, and when the temperature was decreased below 5°C, mycelium growth of A. caulina became extremely slow; thus, both extreme high and low temperatures affected the pathogenicity of A. caulina. Mancozeb and azoxystrobin fungicides were revealed to have had the strongest inhibitory effects on the conidial germination of A. caulina, and in some cases caused malformations in conidial germination. Tebuconazole and difenoconazole had the strongest inhibitory effects on A. caulina mycelial growth and less on the effects on the conidial germination. The results of the present study provide a basis for the recognition and management of quinoa black stem.
Nitrate supplementation enhances exercise performance: A systematic review and meta‐analysis
Authors: Regimbal Riley , Senefeld Jonathon , Wiggins Chad , Dominelli Paolo , Baker Sarah , Joyner Michael
Published: April 2020

Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO3−) supplementation (e.g. beetroot juice) in young, healthy men and women, it is unclear if participant and environmental factors modulate the well‐described ergogenic effects—particularly relevant factors include biological sex, aerobic fitness and fraction of inspired oxygen (FiO2) during exercise. To address this limitation, the literature was systematically reviewed for randomized, cross‐over, placebo‐controlled studies reporting exercise performance outcome metrics with NO3− supplementation in young, healthy adults. There were 2,033 articles identified, and 80 articles met inclusion criteria for the meta‐analysis. Random‐effects meta‐analysis demonstrated that exercise performance was improved with NO3− supplementation compared to placebo (d=0.174, 95% CI [0.120–0.229], P<0.001). Subgroup analyses conducted on biological sex, aerobic fitness and FiO2 demonstrated that the ergogenic effect of NO3− supplementation was: 1) not observed in studies with only women (n=6, d=0.116, 95% CI [−0.126–0.358], P=0.347), 2) not observed in participants with moderate aerobic fitness (less than 45 mL·kg−1·min−1; n=4, d=0.168, 95% CI [−0.134–0.469], P=0.276) or elite aerobic fitness (65 mL·kg−1·min−1 or greater; n=26, d=0.021, 95% CI [−0.103–0.144], P=0.745) and 3) was not modulated by FiO2 (hypoxia: n=17, d=0.214, 95% CI [0.054–0.375], P=0.009 vs. normoxia n=97, d=0.175, 95% CI [0.114–0.237], P<0.001). Together, the meta‐analyses demonstrated a clear ergogenic effect of NO3− supplementation in recreationally‐active, young, healthy men across many different exercise paradigms and NO3− supplementation parameters; however, the effect size of NO3− supplementation was objectively small. Although NO3− supplementation may be effective in moderately fit, healthy men, NO3− supplementation has limited utility as an ergogenic aid in participants that have optimized other training parameters. Mechanistic research and studies incorporating a wide variety of subjects (e.g. women) are needed to advance the study of NO3− supplementation; however, additional descriptive studies of young healthy men may have limited utility.

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