bluuebunny/crossref_metadata_2025 huggingface dataset:
Cumulative cellulolytic enzyme activities and initial litter quality in prediction of cellulose degradation in an alpine meadow of the eastern Tibetan Plateau
Authors: Chen Yamei , Liu Yang , Zhang Jian , Yang Wanqin , Deng Changchun , He Runlian
Published: September 2019

Aims

Plant litter decomposition is a key ecosystem process that determines carbon and nutrient cycling in terrestrial ecosystems. As a main component of litter, cellulose is a vital energy source for the microbes associated with litter decomposition. The important role of cellulolytic enzymes in litter cellulose degradation is well understood, but seasonal patterns of cellulose degradation and whether cumulative enzyme activities and litter quality forecast cellulose degradation in an alpine meadow remain elusive, which limits our understanding of cellulose degradation in herbaceous plant litter.

Methods

A two-year field litterbag experiment involving three dominant species (Ajuga ovalifolia, Festuca wallichanica, and Pedicularis roylei) was conducted in an alpine meadow of the eastern Tibetan Plateau to explore the seasonal patterns of cellulose degradation and how cumulative cellulolytic enzyme activities and initial litter quality impact cellulose degradation.

Important findings

Our study demonstrates that cellulose degraded rapidly and exceeded 50% during the first year, which mainly occurred in the first growing season (31.9%–43.3%). At two years of decomposition, cellulose degradation was driven by cumulative endoglucanase (R2 = 0.70), cumulative cellobiohydrolase (R2 = 0.59) and cumulative 1,4-β-glucosidase (R2 = 0.57). In addition, the concentrations of cellulose, dissolved organic carbon, total phenol, lignin and lignin/N accounted for 52%–78% of the variation in cellulose degradation during the two years of decomposition. The best model for predicting cellulose degradation was the initial cellulose concentration (R2 = 0.78). The enzymatic efficiencies and the allocation of cellulolytic enzyme activities were different among species. The cellulolytic enzyme efficiencies were higher in the litter of F. wallichanica with relatively lower quality. For the complete cellulose degradation of the leaf litter, A. ovalifolia and F. wallichanica required 4-fold and 6.7-fold more endoglucanase activity, 3-fold and 4.5-fold more cellobiohydrolase activity and 1.2-fold and 1.4-fold more 1,4-β-glucosidase activity, respectively, than those required by P. roylei. Our results demonstrated that although microbial activity and litter quality both have significant impacts on cellulose degradation in an alpine meadow, using cellulose concentration to predict cellulose degradation is a good way to simplify the model of cellulose degradation and C cycling during litter decomposition.
Iatrogenic injury to a vesicourachal diverticulum during laparoscopic appendectomy successfully managed conservatively
Authors: Alobaysi Saad , Alsairi Saud , Aljasser Abdullah , Alkhaddam Ahmad , Alshamrani Abdullah
Published: September 2019

A vesicourachal diverticulum is a rare congenital anomaly that arises from the incomplete closure of the urachus at the bladder end. We describe a 12-year-old boy who presented with severe persistent right iliac fossa pain associated with subjective fever, nausea, vomiting, and anorexia. A computed tomography (CT) scan of the abdomen and pelvis revealed findings consistent with appendicitis. The patient underwent a laparoscopic appendectomy; however, his postoperative course was remarkable for a low urine output and urine leakage from the suprapubic port site. A CT cystography showed a vesicourachal diverticulum and conservative management was offered. This management consisted of Foley catheter placement, hourly monitoring of the patient’s urine output, antibiotic prophylaxis, daily laboratory investigations and a cystography performed after 7 days. Overall, injury to the vesicourachal diverticulum is rare, and surgeons should be aware of this rare clinical entity and exercise caution during port placement. Surgeons should also have a high index of suspicion to identify these injuries and appropriately manage the condition early.
Summer Hajj pilgrimage in the era of global warming: a call for vigilance and better understanding of the risks
Authors: Yezli Saber , Khan Anas , Bouchama Abderrezak
Published: September 2019

Hajj, one of the largest and most ethnically and geographically diverse annual mass gatherings in the world, presents many of the risk factors for heat-related illnesses. In the era of global warming, these illnesses are a major health threat at the event, especially while Hajj is in the hot cycle.
The presence of interstellar scintillation in the 15 GHz interday variability of 1158 OVRO-monitored blazars
Authors: Koay J Y , Jauncey D L , Hovatta T , Kiehlmann S , Bignall H E , Max-Moerbeck W , Pearson T J , Readhead A C S , Reeves R , Reynolds C , Vedantham H
Published: September 2019

We have conducted the first systematic search for interday variability in a large sample of extragalactic radio sources at 15 GHz. From the sample of 1158 radio-selected blazars monitored over an ∼10 yr span by the Owens Valley Radio Observatory 40-m telescope, we identified 20 sources exhibiting significant flux density variations on 4-d time-scales. The sky distribution of the variable sources is strongly dependent on the line-of-sight Galactic H α intensities from the Wisconsin H α Mapper Survey, demonstrating the contribution of interstellar scintillation (ISS) to their interday variability. 21 per cent of sources observed through sightlines with H α intensities larger than 10  rayleighs exhibit significant ISS persistent over the ∼10 yr period. The fraction of scintillators is potentially larger when considering less significant variables missed by our selection criteria, due to ISS intermittency. This study demonstrates that ISS is still important at 15 GHz, particularly through strongly scattered sightlines of the Galaxy. Of the 20 most significant variables, 11 are observed through the Orion–Eridanus superbubble, photoionized by hot stars of the Orion OB1 association. The high-energy neutrino source TXS 0506+056 is observed through this region, so ISS must be considered in any interpretation of its short-term radio variability. J0616−1041 appears to exhibit large ∼20 per cent interday flux density variations, comparable in magnitude to that of the very rare class of extreme, intrahour scintillators that includes PKS0405−385, J1819+3845, and PKS1257−326; this needs to be confirmed by higher cadence follow-up observations.
NGTS-7Ab: an ultrashort-period brown dwarf transiting a tidally locked and active M dwarf
Authors: Jackman James A G , Wheatley Peter J , Bayliss Dan , Gill Samuel , Hodgkin Simon T , Burleigh Matthew R , Braker Ian P , Günther Maximilian N , Louden Tom , Turner Oliver , Anderson David R , Belardi Claudia , Bouchy François , Briegal Joshua T , Bryant Edward M , Cabrera Juan , Casewell Sarah L , Chaushev Alexander , Costes Jean C , Csizmadia Szilard , Eigmüller Philipp , Erikson Anders , Gänsicke Boris T , Gillen Edward , Goad Michael R , Jenkins James S , McCormac James , Moyano Maximiliano , Nielsen Louise D , Pollacco Don , Poppenhaeger Katja , Queloz Didier , Rauer Heike , Raynard Liam , Smith Alexis M S , Udry Stéphane , Vines Jose I , Watson Christopher A , West Richard G
Published: September 2019

We present the discovery of NGTS-7Ab, a high-mass brown dwarf transiting an M dwarf with a period of 16.2 h, discovered as part of the Next Generation Transit Survey (NGTS). This is the shortest period transiting brown dwarf around a main or pre-main sequence star to date. The M star host (NGTS-7A) has an age of roughly 55 Myr and is in a state of spin–orbit synchronization, which we attribute to tidal interaction with the brown dwarf acting to spin-up the star. The host star is magnetically active and shows multiple flares across the NGTS and follow-up light curves, which we use to probe the flare–star-spot phase relation. The host star also has an M star companion at a separation of 1.13 arcsec with very similar proper motion and systemic velocity, suggesting that the NGTS-7 system is a hierarchical triple. The combination of tidal synchronisation and magnetic braking is expected to drive on-going decay of the brown dwarf orbit, with a remaining lifetime of only 5–10 Myr.
The contribution from rotating massive stars to the enrichment in Sr and Ba of the Milky Way
Authors: Rizzuti F , Cescutti G , Matteucci F , Chieffi A , Hirschi R , Limongi M
Published: September 2019

Most neutron capture elements have a double production by r- and s-processes, but the question of production sites is complex and still open. Recent studies show that including stellar rotation can have a deep impact on nucleosynthesis. We studied the evolution of Sr and Ba in the Milky Way. A chemical evolution model was employed to reproduce the Galactic enrichment. We tested two different nucleosynthesis prescriptions for s-process in massive stars, adopted from the Geneva group and the Rome group. Rotation was taken into account, studying the effects of stars without rotation or rotating with different velocities. We also tested different production sites for the r-process: magneto rotational driven supernovae and neutron star mergers. The evolution of the abundances of Sr and Ba is well reproduced. The comparison with the the most recent observations shows that stellar rotation is a good assumption, but excessive velocities result in overproduction of these elements. In particular, the predicted evolution of the [Sr/Ba] ratio at low metallicity does not explain the data at best if rotation is not included. Adopting different rotational velocities for different stellar mass and metallicity better explains the observed trends. Despite the differences between the two sets of adopted stellar models, both show a better agreement with the data assuming an increase of rotational velocity toward low metallicity. Assuming different r-process sources does not alter this conclusion.
An extragalactic chromosome map: the intermediate-age SMC cluster Lindsay 1
Authors: Saracino S , Bastian N , Kozhurina-Platais V , Cabrera-Ziri I , Dalessandro E , Kacharov N , Lardo C , Larsen S S , Mucciarelli A , Platais I , Salaris M
Published: September 2019

The discovery of star-to-star abundance variations (a.k.a. multiple populations – MPs) within globular clusters (GCs), which are generally not found in the field or in lower mass open clusters, has led to a search for the unique property of GCs that allow them to host this phenomenon. Recent studies have shown that MPs are not limited to the ancient GCs but are also found in massive clusters with ages down to (at least) 2 Gyr. This finding is important for understanding the physics of the MP phenomenon, as these young clusters can provide much stronger constraints (e.g. on potential age spreads within the clusters) than older ones. However, a direct comparison between ancient GCs and intermediate clusters has not yet been possible due to the different filters adopted in their studies. Here we present new Hubble Space Telescope UV photometry of the 7.5 Gyr, massive Small Magellanic Cloud cluster, Lindsay 1, in order to compare its pseudo colour–colour diagram to that of Galactic GCs. We find that they are almost identical and conclude that the MPs phenomenon is the same, regardless of cluster age and host galaxy.
Play with Closing Markers: Cadential Multivalence in 1960s Prechoruses and Related Schemas
Authors: Heetderks David
Published: September 2019

In 1960s pop/rock, the end of a prechorus often uses text, breakaway from harmonic loops, hypermeter, or a change of melody to heighten expectation for tonic harmony and create structural closure. Songs harness this heightened expectation to underscore the importance of the chorus and illustrate the singer’s lyrics. These closing markers provide a wide range of expressive and formal options by creating various cadential effects, including a closed cadence overlapping with the chorus, an open cadence before the chorus, or—in passages often depicting marked emotional states—conflicting formal cues.
Molecular determinants for enzalutamide-induced transcription in prostate cancer
Authors: Yuan Fuwen , Hankey William , Wu Dayong , Wang Hongyan , Somarelli Jason , Armstrong Andrew J , Huang Jiaoti , Chen Zhong , Wang Qianben
Published: September 2019

Enzalutamide, a second-generation androgen receptor (AR) antagonist, has demonstrated clinical benefit in men with prostate cancer. However, it only provides a temporary response and modest increase in survival, indicating a rapid evolution of resistance. Previous studies suggest that enzalutamide may function as a partial transcriptional agonist, but the underlying mechanisms for enzalutamide-induced transcription remain poorly understood. Here, we show that enzalutamide stimulates expression of a novel subset of genes distinct from androgen-responsive genes. Treatment of prostate cancer cells with enzalutamide enhances recruitment of pioneer factor GATA2, AR, Mediator subunits MED1 and MED14, and RNA Pol II to regulatory elements of enzalutamide-responsive genes. Mechanistically, GATA2 globally directs enzalutamide-induced transcription by facilitating AR, Mediator and Pol II loading to enzalutamide-responsive gene loci. Importantly, the GATA2 inhibitor K7174 inhibits enzalutamide-induced transcription by decreasing binding of the GATA2/AR/Mediator/Pol II transcriptional complex, contributing to sensitization of prostate cancer cells to enzalutamide treatment. Our findings provide mechanistic insight into the future combination of GATA2 inhibitors and enzalutamide for improved AR-targeted therapy.
The impact of biomarkers of acute kidney injury on individual patient care
Authors: Koyner Jay L , Zarbock Alexander , Basu Rajit K , Ronco Claudio
Published: September 2019

Acute kidney injury (AKI) remains a common clinical syndrome associated with increased morbidity and mortality. In the last several years there have been several advances in the identification of patients at increased risk for AKI through the use of traditional and newer functional and damage biomarkers of AKI. This article will specifically focus on the impact of biomarkers of AKI on individual patient care, focusing predominantly on the markers with the most expansive breadth of study in patients and reported literature evidence. Several studies have demonstrated that close monitoring of widely available biomarkers such as serum creatinine and urine output is strongly associated with improved patient outcomes. An integrated approach to these biomarkers used in context with patient risk factors (identifiable using electronic health record monitoring) and with tests of renal reserve may guide implementation and targeting of care bundles to optimize patient care. Besides traditional functional markers, biochemical injury biomarkers have been increasingly utilized in clinical trials both as a measure of kidney injury as well as a trigger to initiate other treatment options (e.g. care bundles and novel therapies). As the novel measures are becoming globally available, the clinical implementation of hospital-based real-time biomarker measurements involves a multidisciplinary approach. This literature review discusses the data evidence supporting both the strengths and limitations in the clinical implementation of biomarkers based on the authors’ collective clinical experiences and opinions.
The South China Sea is not a mini-Atlantic: plate-edge riftingvsintra-plate rifting
Authors: Wang Pinxian , Huang Chi-Yue , Lin Jian , Jian Zhimin , Sun Zhen , Zhao Minghui
Published: September 2019

The South China Sea, as ‘a non-volcanic passive margin basin’ in the Pacific, has often been considered as a small-scale analogue of the Atlantic. The recent ocean drilling in the northern South China Sea margin found, however, that the Iberian model of non-volcanic rifted margin from the Atlantic does not apply to the South China Sea. In this paper, we review a variety of rifted basins and propose to discriminate two types of rifting basins: plate-edge type such as the South China Sea and intra-plate type like the Atlantic. They not only differ from each other in structure, formation process, lifespan and geographic size, but also occur at different stages of the Wilson cycle. The intra-plate rifting occurred in the Mesozoic and gave rise to large oceans, whereas the plate-edge rifting took place mainly in the mid-Cenozoic, with three-quarters of the basins concentrated in the Western Pacific. As a member of the Western Pacific system of marginal seas, the South China Sea should be studied not in isolation on its origin and evolution, but in a systematic context to include also its neighboring counterparts.
Evaluation of Sex Differences in the Elasticity of Demand for Nicotine and Food in Rats
Authors: Chellian Ranjithkumar , Wilson Ryann , Polmann Michaela , Knight Parker , Behnood-Rod Azin , Bruijnzeel Adriaan W
Published: September 2019

Introduction

Animal studies can inform policy regarding nicotine levels in tobacco products and e-cigarette solutions. Increasing the price of nicotine-containing products decreases their use, but it is unknown how the relationship between price and consumption is affected by both sex and nicotine dose.

Methods

A behavioral economics procedure was used to determine the demand elasticity for nicotine in male and female rats. Demand elasticity describes the relationship between price and consumption. A high level of elasticity indicates that consumption is relatively sensitive to increases in price. The rats self-administered a low dose (0.01 mg/kg/inf) or a standard dose (0.03 mg/kg/inf) of nicotine for 9 days under a fixed-ratio (FR) 1 schedule. Then the price (FR schedule) of nicotine was increased, and a demand analysis was conducted. A similar study was conducted with palatable food pellets.

Results

There were no sex differences in nicotine or food intake under the FR1 schedule. However, demand for 0.03 mg/kg/inf of nicotine was more elastic in females than males. Demand for 0.01 mg/kg/inf of nicotine and food was more elastic in males than females.

Conclusions

These findings indicate that there are no differences in nicotine and food intake between males and females when the price is low. When the price of nicotine or food is increased, males maintain their old level of intake longer than females when they have access to a standard dose of nicotine, and females maintain their intake longer when they have access to a low dose of nicotine or food.

Implications

This behavioral economics analysis indicates that there is no sex difference in nicotine intake when the price of nicotine is low. Increasing the price of nicotine decreases nicotine intake in a dose- and sex-specific manner. Males maintain their old level of intake longer when they have access to a standard dose of nicotine and females when they have access to a low dose. This has implications for tobacco regulatory policy. In a regulatory environment where only low nicotine-containing products are allowed, increasing the price of nicotine products may lead to a greater decrease in nicotine use in males than females.
Learning Experiences Within Infectious Diseases Pharmacy Residency Programs in the United States: A Cross-Sectional Survey
Authors: Cho Jonathan C , Crotty Matthew P , Kufel Wesley D , Chahine Elias B , Sofjan Amelia K , Gallagher Jason C , Estrada Sandy J
Published: September 2019

Background

Pharmacists with residency training in infectious diseases (ID) optimize antimicrobial therapy outcomes in patients and support antimicrobial stewardship (AS) programs. Although most ID residencies are accredited and assessed by certain standards, the degree to which these programs are similar is not known.

Methods

A 19-item, cross-sectional, multicentered, electronic survey was distributed via e-mail to pharmacy residency program directors (RPDs) of all 101 second-year postgraduate (PGY-2) ID residency programs in the United States.

Results

Survey responses were collected from 71 RPDs (70.3%); 64.8% were associated with an academic medical center and 97.2% focused primarily in adult ID. Rotations in the microbiology laboratory, adult AS, and adult ID consult were required in 98.6% of residency programs. Only 28.2% of responding programs required pediatric AS and pediatric ID consult rotations. Programs at academic medical centers were more likely to offer immunocompromised host ID consult (P = .003), pediatric ID consult (P = .006), and hospital epidemiology (P = .047) rotations but less frequently offered outpatient AS (P = .003), viral hepatitis clinics (P = .001), and travel medicine clinics (P = .007) rotations compared to programs at nonacademic medical centers. Residents were frequently involved in AS committees (97.2%), pharmacokinetic dosing of antimicrobials (83.1%), precepting pharmacy trainees (80.3%), and performing research projects (91.5%).

Conclusions

The PGY-2 ID pharmacy residency programs demonstrated consistency in required adult ID consult, antimicrobial management activities, committee service, and teaching and research opportunities. Pediatric experiences were less common. The PGY-2 ID residency programs prepare pharmacists to become antimicrobial stewards for adult patients.
Diurnal.plant.tools: Comparative Transcriptomic and Co-expression Analyses of Diurnal Gene Expression of the Archaeplastida Kingdom
Authors: Ng Jonathan Wei Xiong , Tan Qiao Wen , Ferrari Camilla , Mutwil Marek
Published: September 2019

Almost all organisms coordinate some aspects of their biology through the diurnal cycle. Photosynthetic organisms, and plants especially, have established complex programs that coordinate physiological, metabolic and developmental processes with the changing light. The diurnal regulation of the underlying transcriptional processes is observed when groups of functionally related genes (gene modules) are expressed at a specific time of the day. However, studying the diurnal regulation of these gene modules in the plant kingdom was hampered by the large amount of data required for the analyses. To meet this need, we used gene expression data from 17 diurnal studies spanning the whole Archaeplastida kingdom (Plantae kingdom in the broad sense) to make an online diurnal database. We have equipped the database with tools that allow user-friendly cross-species comparisons of gene expression profiles, entire co-expression networks, co-expressed clusters (involved in specific biological processes), time-specific gene expression and others. We exemplify how these tools can be used by studying three important biological questions: (i) the evolution of cell division, (ii) the diurnal control of gene modules in algae and (iii) the conservation of diurnally controlled modules across species. The database is freely available at http://diurnal.plant.tools.
Cytosolic Acetyl-CoA Generated by ATP-Citrate Lyase Is Essential for Acetylation of Cell Wall Polysaccharides
Authors: Zhong Ruiqin , Cui Dongtao , Richardson Elizabeth A , Phillips Dennis R , Azadi Parastoo , Lu Grace , Ye Zheng-Hua
Published: September 2019

Plant cell wall polysaccharides, including xylan, glucomannan, xyloglucan and pectin, are often acetylated. Although a number of acetyltransferases responsible for the acetylation of some of these polysaccharides have been biochemically characterized, little is known about the source of acetyl donors and how acetyl donors are translocated into the Golgi, where these polysaccharides are synthesized. In this report, we investigated roles of ATP-citrate lyase (ACL) that generates cytosolic acetyl-CoA in cell wall polysaccharide acetylation and effects of simultaneous mutations of four Reduced Wall Acetylation (RWA) genes on acetyl-CoA transport into the Golgi in Arabidopsis thaliana. Expression analyses of genes involved in the generation of acetyl-CoA in different subcellular compartments showed that the expression of several ACL genes responsible for cytosolic acetyl-CoA synthesis was elevated in interfascicular fiber cells and induced by secondary wall-associated transcriptional activators. Simultaneous downregulation of the expression of ACL genes was demonstrated to result in a substantial decrease in the degree of xylan acetylation and a severe alteration in secondary wall structure in xylem vessels. In addition, the degree of acetylation of other cell wall polysaccharides, including glucomannan, xyloglucan and pectin, was also reduced. Moreover, Golgi-enriched membrane vesicles isolated from the rwa1/2/3/4 quadruple mutant were found to exhibit a drastic reduction in acetyl-CoA transport activity compared with the wild type. These findings indicate that cytosolic acetyl-CoA generated by ACL is essential for cell wall polysaccharide acetylation and RWAs are required for its transport from the cytosol into the Golgi.
Using Implementation Frameworks to Provide Proactive Physical Therapy for People With Parkinson Disease: Case Report
Authors: Rafferty Miriam R , MacDonald Jillian , Byskosh Alexandria , Sloan Laura , Toledo Santiago , Marciniak Christina , Simuni Tanya
Published: September 2019

Background and Purpose

European clinical practice guidelines recommend physical therapy for people with Parkinson disease (PD) soon after diagnosis to provide education, physical activity advice, and individualized interventions when needed. However, therapy is frequently not used until after gait and balance problems occur. The purpose of this administrative case study is to present the application of a proactive physical therapy (PAPT) approach at 1 rehabilitation center using implementation frameworks to support the (1) implementation process, (2) determinants of implementation success, and (3) implementation evaluation.

Case Description

The PAPT program targeted people with PD before the onset of significant mobility dysfunction. It was initiated in 1 outpatient neurological rehabilitation center. The program used shared decision-making to promote long-term maintenance of independent exercise. The Knowledge-to-Action Framework was used by champions to plan implementation processes. Implementation barriers were addressed using the Consolidated Framework for Implementation Research. The program was evaluated using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework with mixed methods.

Outcomes

In the program’s first year, 38 people were referred, 28 were evaluated, and 20 participated in the 6-month program evaluation. Following PAPT, the number of participants reporting regular participation in aerobic, strengthening, and flexibility exercise approximately doubled, while those engaging in balance activities increased from 1 to 8. They reported a median of 140 minutes of aerobic exercise per week. Implementation barriers included location, insurance coverage, and difficulty scheduling long-term follow-up visits. Participants reported physical and emotional benefits of the program.

Discussion

Implementation frameworks assisted with the implementation and evaluation of a PAPT delivery model that helped people with PD to increase and maintain independent exercise participation.
Effects of an Individualized Exercise Program Plus Behavioral Change Enhancement Strategies for Managing Fatigue in Older People Who Are Frail: Protocol for a Cluster Randomized Controlled Trial
Authors: Liu Justina Y W , Kor Patrick P K , Lee Paul L , Chien Wai T , Siu Parco M , Hill Keith D
Published: September 2019

Background

Although the evidence suggests that general fatigue is a strong indicator of rapid aging, frailty, and disability, general fatigue is undertreated in gerontological care.

Objective

The aim of this study is to investigate whether an individualized exercise program with and without behavioral change enhancement (BCE) strategies for older people who are frail and have general fatigue will reduce their fatigue and symptoms of frailty.

Design

A 3-arm, single-blind, cluster randomized controlled trial registered with ClinicalTrials.gov (NCT03394495) will be conducted.

Setting

The study will be conducted in a community setting.

Participants

Two hundred eighty-five community-dwelling older people with general fatigue will be recruited from 12 district community health centers.

Intervention

People from each center will be randomized to one of three groups. The combined group will receive a 16-week combined intervention consisting of individualized exercise training and the BCE program, plus two booster sessions at 2 and 6 months after the program. The exercise group will receive exercise training and health talks only. The control group will receive health talks only.

Measurements

Outcome measures will be collected at baseline, at the midpoint (week 8) of the program, and then at 1 week, 6 months, and 12 months after the end of the program. The primary outcome---level of fatigue---will be measured using the Multidimensional Fatigue Inventory. Secondary outcomes will include the participants’ frailty status, strength, mobility, exercise self-efficacy, and habitual physical activity.

Limitations

A self-reported level of fatigue will be used.

Conclusions

The effect of exercise and BCE strategies on general fatigue among older people who are frail is not known. This study will be a pioneering interventional study on how general fatigue among older people who are frail can be managed and how fatigue-related frailty can be prevented or minimized.
A simplified radiographic score effectively predicts radiographic progression of early arthritis in a large nationwide French cohort
Authors: Carvajal Alegria Guillermo , Milin Morgane , Gandjbakhch Frédérique , Saraux Alain , Bailly Florian , Jousse-Joulin Sandrine , Schaeverbeke Thierry , Lukas Cédric , Foltz Violaine , Fautrel Bruno , Devauchelle-Pensec Valérie
Published: September 2019

Objective

Evaluating radiographic progression is a key component of the follow-up of patients with RA. Existing scores are ill-suited to everyday clinical practice. The objective here was to validate a new simplified radiographic score (SRS) for evaluating radiographic progression in patients with early arthritis.

Methods

Patients with arthritis of <6 months’ duration were included in the large, prospective, nationwide, French ESPOIR cohort. Radiographs of the hands and feet were obtained at inclusion then 1 and 5 years later. The modified Sharp scores and SRS were determined by blinded readers. Interobserver reliability and intraobserver repeatability of each score, as well as agreement between the two scores, were assessed by computing the intraclass correlation coefficients. The rates of progression over the first year and the next 4 years were determined.

Results

The 506 patients with complete data for the first 5 years were included. At inclusion, the intraclass correlation coefficient between the two scores was good for erosions (0.715, P < 0.001), joint space narrowing (0.892, P < 0.001) and the total score (0.896, P < 0.001). Agreement between the two scores was also good for radiographic progression after 1 year (0.781, P < 0.001). The SRS had good positive and negative predictive values for slow and for rapid progression. SRS determination was less time consuming.

Conclusion

The SRS is effective for monitoring radiographic progression in early arthritis and is easier to use and less time-consuming than the Sharp score. The usefulness of the SRS in clinical practice deserves further evaluation.
The active construction of passive investors: roboadvisors and algorithmic ‘low-finance’
Authors: Hayes Adam S
Published: September 2019

How does algorithmic finance operate in society as it crosses the threshold into the hands of lay investors? This article builds on original ethnographic research into a new class of algorithmic trading programs known as ‘roboadvisors’—inexpensive, automated, digital financial platforms that enable ordinary people to invest very small minimum amounts and that rely to a large extent on passive, index strategies that follow the prescripts of Modern Portfolio Theory. The main argument of the article is that roboadvisors, representing an ethos of ‘low-finance’, are actively constructing passive investors by disciplining them through technologies that embody canonical models of financial economics. Roboadvisors and their algorithms reconfigure their users and objectify them through automating investment decisions and enforcing a principle of ‘don’t do’ vis-à-vis the market. Implications that bear on agency, market structure and regulatory regimes are discussed.
Identification of Candidate Risk Factor Genes for Human Idelalisib Toxicity Using a Collaborative Cross Approach
Authors: Mosedale Merrie , Cai Yanwei , Eaddy John Scott , Corty Robert W , Nautiyal Manisha , Watkins Paul B , Valdar William
Published: September 2019

Idelalisib is a phosphatidylinositol 3-kinase inhibitor highly selective for the delta isoform that has shown good efficacy in treating chronic lymphocytic leukemia and follicular lymphoma. In clinical trials, however, idelalisib was associated with rare, but potentially serious liver and lung toxicities. In this study, we used the Collaborative Cross (CC) mouse population to identify genetic factors associated with the drug response that may inform risk management strategies for idelalisib in humans. Eight male mice (4 matched pairs) from 50 CC lines were treated once daily for 14 days by oral gavage with either vehicle or idelalisib at a dose selected to achieve clinically relevant peak plasma concentrations (150 mg/kg/day). The drug was well tolerated across all CC lines, and there were no observations of overt liver injury. Differences across CC lines were seen in drug concentration in plasma samples collected at the approximate Tmax on study Days 1, 7, and 14. There were also small but statistically significant treatment-induced alterations in plasma total bile acids and microRNA-122, and these may indicate early hepatocellular stress required for immune-mediated hepatotoxicity in humans. Idelalisib treatment further induced significant elevations in the total cell count of terminal bronchoalveolar lavage fluid, which may be analogous to pneumonitis observed in the clinic. Genetic mapping identified loci associated with interim plasma idelalisib concentration and the other 3 treatment-related endpoints. Thirteen priority candidate quantitative trait genes identified in CC mice may now guide interrogation of risk factors for adverse drug responses associated with idelalisib in humans.
High-efficient utilization and uptake of N contribute to higher NUE of ‘Qinguan’ apple under drought and N-deficient conditions compared with ‘Honeycrisp’
Authors: Wang Qian , Liu Changhai , Huang Dong , Dong Qinglong , Li Pengmin , Ma Fengwang
Published: September 2019

Drought and nitrogen (N) deficiency are common factors that limit apple production in the Loess Plateau region of China. Different apple cultivars respond to drought and low N differently; however, the mechanism that underlies the difference in nitrogen-use efficiency (NUE) under drought conditions is not well understood. In this study, by comparing the physiological responses of two apple (Malus domestica Borkh.) cultivars with contrasting NUE, ‘Qinguan’ (higher NUE) and ‘Honeycrisp’ (lower NUE), under low N and drought conditions, we discovered that, ‘Qinguan’ had larger stomatal apertures, higher chlorophyll fluorescence levels, more active N metabolism and antioxidant enzymes, higher abscisic acid and auxin concentrations, larger root size and more efficient N uptake mediated by higher expression of MdNRT2.4 in rootstock than that of ‘Honeycrisp’. Additionally, we experimentally confirmed that MdNRT2.4 enhanced low N and osmotic stress tolerance in Arabidopsis when being overexpressed. Taken together, our findings shed light on the mechanism that underlies the difference in NUE of apple under drought and N-deficient conditionss and provide MdNRT2.4 as a candidate gene for future genetic engineering.
Evaluation of the effectiveness of community health workers in the fight against malaria in the Central African Republic (2012–2017)
Authors: Ferdinand Djerandouba Yotobumbeti , Nadlaou Bessimbaye , Samuel Nzalapan , Oscar Bekaka Youlet , Raphael Mbailao , Christophe Ndoua , Lopes Sergio , Allan Richard
Published: September 2019

Background

This last decade’s ongoing conflict in the Central African Republic (CAR) has led to gradual and continuous destruction of health services. With severe gaps in qualified health professionals, community health workers (CHWs) have become essential to ensuring health care access to the affected population. This article aims to evaluate the effectiveness of a 10-y CHW program in the CAR.

Methods

Routine case management data from CHWs were collected in the Paoua district from January 2012 to December 2017 and analysed. Structured interviews were conducted in the Paoua and Carnot health districts among individuals from three different groups (health service beneficiaries, CHWs and health facility managers).

Results

From 2012 to 2017, 353 948 people consulted for malaria suspicion with CHWs and 86% were found to be malaria positive after a rapid diagnostic test. Among those diagnosed patients, 98.5% received adequate treatment and nearly 1.5% were referred to health facilities. Also, 94.5% of respondents identified fever as the major malaria symptom. About 70% of the population could identify three malaria signs/symptoms and 84.4% accepted and used CHW services. Interviews with CHWs revealed that 45.8% of them received at least four training sessions per month as part of their capacity building.

Conclusions

CHWs can be a resourceful solution when other health professional are scarce. This study showed that CHWs are not only able to deliver curative and preventive health services, but they are also well accepted by the served communities.
Fusarium Crown Rot of Winter Wheat Influenced by Resource Competition Near a Tree Windbreak
Authors: Smiley Richard W. , Machado Stephen
Published: September 2019

Fusarium crown rot becomes most severe when wheat is stressed for water near the time of anthesis. This research examined the potential to study crown rot in the gradient of resource competition near a tree windbreak. Winter wheat was planted for 2 years into a field infested by Fusarium pseudograminearum and bordered by 17-m-high Austrian pines. Crown rot, plant growth and yield, and soil water content were evaluated at six distances (5 to 46 m) perpendicular to the tree line in strip plots inoculated or not inoculated with the pathogen. Crown rot was minor (<5% whiteheads) in noninoculated strips and greater in inoculated strips (26 to 35%) in a 21-m zone from 9 to 30 m from the tree line (0.5–1.8 times the tree height; 0.5–1.8H). At 46 m (2.7H), crown rot was similar in noninoculated and inoculated strips (2 to 5% whiteheads). Whiteheads and culm browning were roughly the reverse of soil water depletion by tree roots. Grain yield at 23 m compared with 46 m was reduced by 33 to 35% in noninoculated plots and by 43 to 49% in inoculated plots. It is possible to study associations between water stress and Fusarium crown rot in the zone of resource competition near windbreaks.
Physiological Response of Cape Gooseberry Seedlings to Three Biological Control Agents Under Fusarium oxysporum f. sp. physali Infection
Authors: Chaves-Gómez José Luis , Chavez-Arias Cristian Camilo , Cotes Prado Alba Marina , Gómez-Caro Sandra , Restrepo-Díaz Hermann
Published: September 2019

Cape gooseberry (Physalis peruviana) fruit has gained recognition owing to its nutritional value and versatility to be consumed processed or as a fresh product. These characteristics have made it an important product in both national and international markets. One of the main limitations for this crop is Fusarium wilt caused by the fungus Fusarium oxysporum f. sp. physalis, for which biological control is emerging as an alternative to conventional management with chemical synthesis products. However, information on the effect that biological control agents have on the growth and development of plants is scarce. In this research, the physiological response of cape gooseberry plants (stomatal conductance, leaf water potential, growth parameters, total chlorophyll, carotenoid, and proline and malondialdehyde contents) to the treatment with three potential biocontrol agents (BCAs) Trichoderma koningiopsis, Trichoderma virens, and Bacillus velezensis was determined. The study was conducted under greenhouse conditions; F. oxysporum was inoculated in the soil, and BCAs were soil drenched in the germination and transplanting stages. Plants inoculated with the pathogen and plants without inoculation were used as controls. It was found that the plants inoculated and treated with T. virens showed the lowest disease levels (area under the disease progress curve of 48.5 and disease severity index of 2.1). Additionally, they showed a lower water potential (−0.317 Mpa), a greater leaf area (694.7 cm2), and a higher stomatal conductance (110.3 mmol m−2 s−1) compared with the control. Consequently, it can be concluded that T. virens can be a good candidate for the management of Fusarium wilt in the cape gooseberry crop.
Screening Tall Fescue for Resistance to Rhizoctonia solani and Rhizoctonia zeae Using Digital Image Analysis
Authors: Sykes Virginia R. , Horvath Brandon J. , McCall David S. , Baudoin Antonius B. , Askew Shawn D. , Goatley James M. , Warnke Scott E.
Published: September 2019

Brown patch, caused by Rhizoctonia solani, is a destructive disease on tall fescue. Compared with R. solani, Rhizoctonia zeae causes indistinguishable symptoms in the field but varies in geographic distribution. This may contribute to geographic variability observed in the resistance response of improved brown patch–resistant cultivars. This study examined R. solani and R. zeae susceptibility of four cultivars, selected based on brown patch performance in the National Turfgrass Evaluation Program (NTEP), and nine plant introductions (PIs). Twenty genotypes per PI/cultivar were evaluated by using four clonal replicates in a randomized complete block design. Plants were inoculated under controlled conditions with two repetitions per pathogen. Disease severity was assessed digitally in APS Assess, and analysis of variance and correlations were performed in SAS 9.3. Mean disease severity was higher for R. solani (65%) than for R. zeae (49%) (P = 0.0137). Interaction effects with pathogen were not significant for PI (P = 0.0562) but were for genotype (P < 0.001). Moderately to highly resistant NTEP cultivars compared with remaining PIs exhibited lower susceptibility to R. zeae (P < 0.0001) but did not differ in susceptibility to R. solani (P = 0.7458). Correlations between R. solani and R. zeae disease severity were not significant for either PI (R = 0.06, P = 0.8436) or genotype (R = 0.11, P = 0.09). Breeding for resistance to both pathogens could contribute to a more geographically stable resistance response. Genotypes were identified with improved resistance to R. solani (40), R. zeae (122), and both pathogens (26).
Mettl17, a regulator of mitochondrial ribosomal RNA modifications, is required for the translation of mitochondrial coding genes
Authors: Shi Zhennan , Xu Siyuan , Xing Shenghui , Yao Ke , Zhang Lei , Xue Luxi , Zhou Peng , Wang Ming , Yan Guoquan , Yang Pengyuan , Liu Jing , Hu Zeping , Lan Fei
Published: September 2019

Embryonic stem cells (ESCs) are pluripotent stem cells with the ability to self‐renew and to differentiate into any cell types of the 3 germ layers. Recent studies have demonstrated that there is a strong connection between mitochondrial function and pluripotency. Here, we report that methyltransferase like (Mettl) 17, identified from the clustered regularly interspaced short palindromic repeats knockout screen, is required for proper differentiation of mouse embryonic stem cells (mESCs). Mettl17 is located in mitochondria through its N‐terminal targeting sequence and specifically interacts with 12S mitochondrial ribosomal RNA (mt‐rRNA) as well as small subunits of mitochondrial ribosome (MSSUs). Loss of Mettl17 affects the stability of both 12S mt‐rRNA and its associated proteins of MSSUs. We further showed that Mettl17 is an S‐adenosyl methionine (SAM)‐binding protein and regulates mitochondrial ribosome function in a SAM‐binding–dependent manner. Loss of Mettl17 leads to around 70% reduction of m4C840 and 50% reduction of m5C842 of 12S mt‐rRNA, revealing the first regulator of the m4C840 and indicating a crosstalk between the 2 nearby modifications. The defects of mitochondrial ribosome caused by deletion of Mettl17 lead to the impaired translation of mitochondrial protein‐coding genes, resulting in significant changes in mitochondrial oxidative phosphorylation and cellular metabolome, which are important for mESC pluripotency.—Shi, Z., Xu, S., Xing, S., Yao, K., Zhang, L., Xue, L., Zhou, P., Wang, M., Yan, G., Yang, P., Liu, J., Hu, Z., Lan, F. Mettl17 a regulator of mitochondrial ribosomal RNA modifications is required for the translation of mitochondrial coding genes. FASEB J. 33, 13040–13050 (2019). www.fasebj.org
Effect of Polyethylene-glycolated Carboxyhemoglobin on Renal Microcirculation in a Rat Model of Hemorrhagic Shock
Authors: Guerci Philippe , Ergin Bulent , Kapucu Aysegul , Hilty Matthias P. , Jubin Ronald , Bakker Jan , Ince Can
Published: September 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Primary resuscitation fluid to treat hemorrhagic shock remains controversial. Use of hydroxyethyl starches raised concerns of acute kidney injury. Polyethylene-glycolated carboxyhemoglobin, which has carbon monoxide–releasing molecules and oxygen-carrying properties, was hypothesized to sustain cortical renal microcirculatory Po
2 after hemorrhagic shock and reduce kidney injury.

Methods

Anesthetized and ventilated rats (n = 42) were subjected to pressure-controlled hemorrhagic shock for 1 h. Renal cortical Po
2 was measured in exposed kidneys using a phosphorescence quenching method. Rats were randomly assigned to six groups: polyethylene-glycolated carboxyhemoglobin 320 mg · kg−1, 6% hydroxyethyl starch (130/0.4) in Ringer’s acetate, blood retransfusion, diluted blood retransfusion (~4 g · dl−1), nonresuscitated animals, and time control. Nitric oxide and heme oxygenase 1 levels were determined in plasma. Kidney immunohistochemistry (histologic scores of neutrophil gelatinase-associated lipocalin and tumor necrosis factor-α) and tubular histologic damages analyses were performed.

Results

Blood and diluted blood restored renal Po
2 to 51 ± 5 mmHg (mean difference, −18; 95% CI, −26 to −11; P < 0.0001) and 47 ± 5 mmHg (mean difference, −23; 95% CI, −31 to −15; P < 0.0001), respectively, compared with 29 ± 8 mmHg for hydroxyethyl starch. No differences between polyethylene-glycolated carboxyhemoglobin and hydroxyethyl starch were observed (33 ± 7 mmHg vs. 29 ± 8 mmHg; mean difference, −5; 95% CI, −12 to 3; P = 0.387), but significantly less volume was administered (4.5 [3.3–6.2] vs. 8.5[7.7–11.4] ml; mean rank difference, 11.98; P = 0.387). Blood and diluted blood increased the plasma bioavailability of nitric oxide compared with hydroxyethyl starch (mean rank difference, −20.97; P = 0.004; and −17.13; P = 0.029, respectively). No changes in heme oxygenase 1 levels were observed. Polyethylene-glycolated carboxyhemoglobin limited tubular histologic damages compared with hydroxyethyl starch (mean rank difference, 60.12; P = 0.0012) with reduced neutrophil gelatinase-associated lipocalin (mean rank difference, 84.43; P < 0.0001) and tumor necrosis factor-α (mean rank difference, 49.67; P = 0.026) histologic scores.

Conclusions

Polyethylene-glycolated carboxyhemoglobin resuscitation did not improve renal Po
2 but limited tubular histologic damages and neutrophil gelatinase-associated lipocalin upregulation after hemorrhage compared with hydroxyethyl starch, whereas a lower volume was required to sustain macrocirculation.