bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal survival costs in an asocial mammal
Authors: Kanaziz Rachel , Huyvaert Kathryn P. , Wells Caitlin P. , Van Vuren Dirk H. , Aubry Lise M.
Published: May 2022

Maternal characteristics, social dynamics, and environmental factors can all influence reproduction and survival and shape trade‐offs that might arise between these components of fitness. Short‐lived mammals like the golden‐mantled ground squirrel (GMGS; Callospermophilus lateralis) tend to maximize effort toward current reproduction at the expense of survival but may be complicated by other aspects of the species’ life history and environment. Here, we use 25 years of data (1995–2020) collected from a population of GMGS at the Rocky Mountain Biological Research Laboratory in Gothic, Colorado, to test the effect of several maternal characteristics (e.g., age, experience, and timing of litter emergence), social context (e.g., litter sex ratio and kin density), and environmental context (e.g., date of bare ground and length of vegetative growing season) on survival of reproductive female GMGS using Cox proportional hazard models. Our results indicated that social dynamics (i.e., density) and environmental conditions (i.e., standardized first day of permanent snow cover and length of growing season) explained significant variation in annual maternal survival, while maternal characteristics did not. A higher density of related breeding females and the total number of females (both related and unrelated to the focal mother) were associated with an increase in the mortality hazard. A later standardized date of the first day of permanent snow cover and a shorter growing season both reduced the maternal mortality hazard. Together, our results suggest that factors extrinsic to the squirrels affect maternal survival and thus may also influence local population growth and dynamics in GMGS and other short‐lived, territorial mammal species.
Trophic interactions and feedbacks maintain intact and degraded states of Hawaiian tropical forests
Authors: Yelenik Stephanie , Rose Eli , Paxton Eben H.
Published: May 2022

Feedbacks within ecosystems can lead to internal reinforcement of the current state providing ecosystem resilience. Often, multiple biotic interactions across trophic levels play a role in such feedbacks, yet these are generally studied independently, obscuring the relative importance of interactions among different factors. We look at various potential feedbacks in intact and degraded mesic forests on Hawaiʻi Island where managers have planted nativeAcacia koa(koa) trees in an attempt to jumpstart succession in former cattle pastures. These restoration forests, however, have not undergone secondary succession, instead maintaining a koa overstory with an exotic pasture grass understory. We contrasted different trophic level processes that influence the capacity for natural understory regeneration: feedbacks between bird‐mediated seed rain and fruiting understory (“top‐down”), as well as links between understory composition and microhabitats for native seed germination (“bottom‐up”). We quantified bird‐mediated seed rain under canopy trees along transects spanning intact, fragmented, and restoration forests. Along these transects, we established plots around focal overstory trees to measure abundance of fruiting understory species, ground cover (e.g., exotic grass, bryophyte), and obtained estimates of bird density to evaluate the contribution of each of these factors to seedling abundance. We also used a factorial seed addition/grass removal experiment to directly compare the influence of seed rain and germination substrate. We found evidence of both top‐down and bottom‐up feedbacks that reinforced the current state of each forest type. In the intact and fragmented forests, the combination of comparatively high seed rain and ample germination substrate is likely critical for maintaining a diverse forest system. In contrast, exotic grasses exhibit priority effects in restoration forests, inhibiting seed germination and effectively negating any benefits that could be derived from bird‐mediated seed rain. Such internal reinforcement suggests that active, rather than passive, restoration would be beneficial to increase forest diversity in restoration areas.
Fish and invertebrate use of restored vs. natural oyster reefs in a shallow temperate latitude estuary
Authors: Grabowski Jonathan H. , Baillie Christopher J. , Baukus Adam , Carlyle Rachael , Fodrie F. Joel , Gittman Rachel K. , Hughes A. Randall , Kimbro David L. , Lee Juhyung , Lenihan Hunter S. , Powers Sean P. , Sullivan Kevin
Published: May 2022

Coastal marine habitats continue to be degraded, thereby compelling large‐scale restoration in many parts of the world. Whether restored habitats function similarly to natural habitats and fully recover lost ecosystem services is unclear. In estuaries, oyster reefs have been degraded by multiple anthropogenic activities including destructive fishing practices and reduced water quality, motivating restoration to maintain oyster fisheries and other ecosystem services, often at relatively high cost. We compared fish and invertebrate communities on recently restored (0–1 year post‐restoration), older restored (3–4 years post‐restoration), and natural oyster reefs to determine if and when restored reefs support functionally similar faunal communities. To test the influence of landscape setting on the faunal communities, the restored and natural reefs, as well as a control without reef present, were distributed among three landscapes (on the edge of salt marsh away from seagrass [salt marsh landscape], on mudflats [mudflat landscape], and near to seagrass and salt marsh [seagrass landscape]). Oyster density and biomass were greatest on restored reef habitat, as were those of non‐oyster bivalve species. Total abundance of invertebrates was much greater on oyster reefs than in control plots, regardless of reef or landscape type, yet were frequently highest on older restored reefs. Meanwhile, juvenile fish densities were greatest on natural reefs, at intermediate densities on older restored reefs, and least abundant on controls. When comparing the effects of reef age and landscape setting, juvenile fish densities were greatest on younger reefs within the mudflat landscape. Collectively, these results indicate that oyster reefs harbor higher densities of resident invertebrate prey, which may explain why reef habitat is also important for juvenile fish. Laboratory and field experiments supported the notion that gag grouper (a predatory demersal fish) forage more effectively on oyster reefs than on unstructured mud bottom, whereas our experiments suggest that flounders that utilize oyster reefs likely forage on adjacent mud bottom. Because landscape setting influenced fish and invertebrate communities on restored reefs, the ecological consequences of landscape setting should be incorporated into restoration decision making and site selection to enhance the recovery of ecosystem goods and services.
The researcher's lament: Why do they ignore my science?
Authors: Bisbal Gustavo A.
Published: May 2022

The researcher's lament is shared by many environmental and conservation scientists who complain about the little support they receive for their research proposals during the review and selection process. Understandably, any hopes of having their anticipated scientific findings applied toward the formulation of environmental management decisions or natural resource policy action are shattered. They attribute this lack of endorsement to shortcomings and limitations among decision makers and proposal selection officials when, in many cases, the rejection of project proposals is often a function of a handful of self‐inflicted failures by applied scientists who anchor themselves stubbornly to doomed approaches. Familiar deficiencies in their research proposals perpetuate the disconnect between the enterprise of science and real‐world resource management challenges. Researchers themselves can affect conditions that turn up the appetite for their scientific endeavors as a more meaningful component of the decision‐making process, namely, to stage and deliver science that is more readily “actionable.” Perhaps it is time for them to consider a course correction to improve the viability of their actionable science proposals. A few basic steps may help rejigger the science planning process in this direction and, consequently, help avoid the researcher's lament. The likelihood of gaining support during the proposal review and award adjudication process, and securing practical application of scientific products, increases when the products are (1) the result of active engagement of researchers with decision makers; (2) better connected to social and political priorities; (3) clearly designed to inform specific management decisions; and (4) tailored to fit the needs of targeted end users. These considerations and activities exist beyond the comfort zone of many environmental or conservation scientists. Yet, those who adopt them will spend less time lamenting rejection and become more influential in the production of actionable knowledge.
Prognostic significance of serum potassium in patients hospitalized for acute heart failure
Authors: Lombardi Carlo Mario , Carubelli Valentina , Peveri Giulia , Inciardi Riccardo Maria , Pagnesi Matteo , Ravera Alice , Tomasoni Daniela , Garafa Emirena , Oriecuia Chiara , Specchia Claudia , Metra Marco
Published: May 2022

Aim

We investigated the prognostic significance of serum potassium abnormalities at discharge in patients hospitalized for acute heart failure (AHF).

Methods and results

In a retrospective analysis, we included 926 patients hospitalized for AHF, stratified by serum potassium levels at discharge as hypokalaemia (<3.5 mEq/L), normokalaemia (3.5–5.0 mEq/L), and hyperkalaemia (>5.0 mEq/L). The primary endpoint was all‐cause death at 1 year since hospital discharge. At discharge, 40 patients had hypokalaemia (4.3%), 840 normokalaemia (90.7%), and 46 hyperkalaemia (5.0%). Patients with hyperkalaemia at discharge were more frequently men, had more signs of congestion, and lower LVEF while patients with hypokalaemia were more likely to be women with HFpEF. Treatment with ACEi/ARBs and MRAs ≥50% of target dose at discharge was similar across groups. One year all‐cause death occurred in 10% of the patients with hypokalaemia, 13.9% of those with normokalaemia, and 30.4% of those with hyperkalaemia (P = 0.006). After adjustment for covariates, including renal function, background treatment, and baseline potassium level, hyperkalaemia resulted an independent predictor of the primary endpoint (HR 1.96, 95% IC [1.01–3.82]; P = 0.048).

Conclusions

In patients with AHF, the presence of hyperkalaemia at discharge is an independent predictor of 1 year all‐cause death.
Prognostic relevance of B‐type natriuretic peptide in patients with moderate mixed aortic valve disease
Authors: Onishi Hirokazu , Naganuma Toru , Izumo Masaki , Ouchi Toru , Yuki Haruhito , Mitomo Satoru , Nakamura Sunao
Published: May 2022

Aims

Data on B‐type natriuretic peptide (BNP) levels and adverse outcomes in patients with moderate mixed aortic valve disease (MAVD), defined as moderate aortic stenosis (AS) and regurgitation (AR), are scarce. Therefore, this study investigated the impact of BNP on the clinical outcomes in such patients.

Methods and results

Clinical data from 81 patients (mean age, 74.1 ± 6.8 years; 50.6%, men) treated for moderate MAVD and left ventricular ejection fraction (LVEF) ≥ 50% during 2010–2018 were retrospectively analysed. Specific echocardiographic data of the study patients were LVEF of 57.8 ± 5.0%, aortic valve index of 0.64 ± 0.04 cm2/m2, peak aortic valve velocity of 3.38 ± 0.29 m/s, and AR vena contracta width of 4.2 ± 0.7 mm. The median BNP level was 61.4 pg/mL (interquartile range, 29.7–109.9). The primary endpoint was a composite of all‐cause death, heart failure hospitalization, and aortic valve replacement, and its cumulative incidence at 5 years was 57.7%. Multivariable analysis revealed that age (hazard ratio, 1.079; 95% confidence interval, 1.028–1.133; P = 0.002) and BNP levels (hazard ratio, 1.028; 95% confidence interval, 1.003–1.053; P = 0.027) were significantly related to the endpoint; specifically, BNP > 61.4 pg/mL had significantly higher incidence rates of the endpoint than those with a BNP ≤ 61.4 pg/mL (70.3% vs. 45.5% at 5 years; P = 0.018). Compared with patients with BNP ≤ 61.4 pg/mL, those with BNP > 61.4 pg/mL had significantly worse left ventricular global longitudinal strain (−17.1 ± 3.6% vs. −18.7 ± 2.6%; P = 0.029), along with higher left ventricular mass index (116.9 ± 27.8 g/m2 vs. 103.5 ± 19.7 g/m2; P = 0.014), relative wall thickness (0.45 ± 0.07 vs. 0.42 ± 0.05; P = 0.022), left atrial volume index (46.0 ± 28.4 mL/m2 vs. 31.4 ± 10.3 mL/m2; P = 0.003), pulmonary artery systolic pressure (32.6 ± 9.7 mmHg vs. 28.2 ± 4.7 mmHg; P = 0.011), and prevalence of moderate or greater tricuspid regurgitation (15.0% vs. 0.0%; P = 0.012).

Conclusions

Patients with moderate MAVD are at higher risk of unfavourable clinical outcomes, and age and BNP are independently related to the occurrence of adverse events. High BNP levels may reflect extravalvular cardiac damage in patients with moderate MAVD.
Stabilization of Ethynyl‐Substituted Aryl‐λ3‐Iodanes by Tethered N‐Heterocylces**
Authors: Kuczmera Thomas J. , Boelke Andreas , Nachtsheim Boris J.
Published: May 2022

A systematic investigation of ethynyl N‐heterocycle‐substituted‐λ3‐iodanes (ENHIs) is presented. In a straightforward one‐pot synthesis these novel reagents can be obtained in high yields bearing a variety of N‐heterocycles. Their reactivity as electrophilic alkyne group transfer reagents was benchmarked in well‐established and novel inter‐ and intramolecular group transfer reactions.
Flow Conditions‐Controlled Divergent Oxidative Cyclization of Reticuline‐Type Alkaloids to Aporphine and Morphinandienone Natural Products
Authors: Bali Judicaël Tra Bi , Abollé Abollé , Coeffard Vincent , Felpin François‐Xavier
Published: May 2022

Described herein is a divergent continuous‐flow approach for the biomimetic oxidative cyclization of reticuline‐type alkaloids to aporphine and morphinandienone natural products using hypervalent iodine(III) reagents. The method was based on the detailed knowledge of the reaction mechanisms in order to develop robust reaction conditions toward the selective synthesis of either aporphine or morphinandienone natural products. In this frame, we exploited the ability of HFIP to stabilize radical cation intermediates and to activate hypervalent iodine(III) oxidants for the flow synthesis of aporphine natural products such as glaucine, rogersine and nantenine. On the other hand, we established that PhI(OAc)(OTf), prepared by action of TMSOTf on PhI(OAc)2, was a powerful oxidant for the synthesis of morphinandienone natural products such as sebiferine and amurine.
Palladium‐Catalyzed Synthesis of Alkylcarbazoles and Their Identification in Petroleum and Source Rocks**
Authors: Theumer Gabriele , Bauer Ingmar , Jäger Anne , Schwark Lorenz , Knölker Hans‐Joachim
Published: May 2022

We describe the synthesis of seven C2‐alkylcarbazoles via a sequence of Buchwald–Hartwig coupling of arylamines with aryl halides followed by oxidative cyclization of the resulting diarylamines. Methyl groups at the positions 4 and 5 were introduced by taking advantage of the ortho‐directed palladation of meta‐pivaloyloxy‐substituted diarylamines and subsequent conversion of the pivaloyloxy to methyl groups through Stille coupling of intermediate triflates. The obtained ethyl‐ and dimethylcarbazoles served as analytical standards for their identification in petroleum samples and source rocks.
Independent development and validation of a novel six‐color fluorescence multiplex panel including 61 diallelic DIPs and 2 miniSTRs for forensic degradation sample
Authors: Liu Yanfang , Mei Shuyan , Jin Xiaoye , Zhao Ming , Zhu Bofeng
Published: May 2022

Current forensic DNA profiles are obtained based on analyses of PCR product sizes or DNA sequence polymorphisms. Sometimes routine forensic analysis using short tandem repeat (STR) generates unsuccessful DNA testing result if the biological sample encountered is excessively degraded and low‐template DNA. Herein, a new six‐color fluorescence labeling system, including 59 autosomal diallelic deletion or insertion polymorphisms (DIPs), 2 miniSTRs, 2 Y‐chromosome DIPs, and 1 Amelogenin gene with the amplicon sizes of less than 200 bp, was self‐developed. According to the validation guidelines for DNA analysis methods formulated by the Scientific Working Group on DNA Analysis Methods, the validation studies have also been carried out for the multiplex system. This novel panel possessed the features of strong stability, high sensitivity, and good specificity, which was especially suitable for the forensic degraded and mixed sample detections. The cumulative power of exclusion and cumulative matching probability of the system were 0.9999978 and 9.833E‐28, respectively, in Han Chinese in Hunan, China. Moreover, this system will be an effective new tool that can be independently applied to forensic personal identification and paternity testing in the populations from the East Asia region, even from the South Asia, America, and Europe regions. The system can also contribute to population phylogenetic affinity and genetic structure analyses among different populations.
Normalization methods for spatio‐temporal analysis of environmental performance: Revisiting the Min–Max method
Authors: Mazziotta Matteo , Pareto Adriano
Published: May 2022

Over the last few years, composite indices for ranking or assessing country performance in a wide variety of complex phenomena, such as environmental sustainability, have gained a lot of popularity. However, not all indices allow for detailed spatio‐temporal analyses. For instance, if individual indicators to be aggregated are normalized by the Min–Max method, they are converted to a common scale with a range of [0, 1] and it can be difficult to appreciate any absolute change in country performance at the extremes of the range (i.e., when a country scores 0 to 1). In this article, an alternative method for normalizing data in a three‐way array of the type units × variables × times, is considered. It normalizes the range of individual indicators, similarly to the Min–Max method, but uses a common reference that allows to “center” them, without forcing them into a closed range. An application to renewable energy consumption data is also shown.
Co‐production of bioethanol and commercially important exopolysaccharides from the marine cyanobacterium Synechococcus elongatusBDU 10144 in a novel low‐cost seawater‐fertilizer‐based medium
Authors: Chandra Neha , Mallick Nirupama
Published: May 2022

The production of bioethanol by cyanobacteria can become economically sustainable if other valuable commercial products, such as exopolysaccharides (EPS), are produced simultaneously. This study investigates the feasibility of producing bioethanol and the commercially important EPS from a non‐nitrogen fixing marine cyanobacterium, Synechococcus elongatus BDU 10144 in a novel low‐cost seawater‐fertilizer medium for the development of a biorefinery strategy. Herein, agricultural fertilizer diammonium phosphate (DAP) (nitrogen source), magnesium sulfate (MgSO4) and potassium were optimized by the central composite design to produce maximum biomass and carbohydrate accretion. The optimal physical conditions for attaining maximum growth and carbohydrate accumulation were determined to be pH 10, 50 μmol m−2 s−1 (light intensity) and 25°C. Further, different concentrations of seawater were mixed with the optimized fertilizer‐salts, and it was observed that 70% of seawater mixed with the optimized fertilizer‐salts (hereafter FSW medium) was an optimum condition for growing the test cyanobacterium, which ultimately reduced the cost of the medium by >40 times compared to the standard artificial seawater nutrient (ASN‐III) medium. Under the optimal conditions, the maximum biomass (1.79 g/L) and carbohydrate (702.4 mg/L) yield obtained were ~1.7 and 2.2 times higher than the ASN‐III. The yield of bioethanol was noted to be 318.1 mg/L, which was ~2.3 times greater than ASN‐III. The commercially important EPS was obtained from the discarded supernatant (0.28 g/L), which was ~1.6 times higher in the FSW medium. Thus, the present investigation paves a way forward for mass cultivation of the S. elongatus BDU 1044 in the novel FSW medium for the cost‐efficient and sustainable development of a biorefinery concept.
Optimization of flame stabilization methods in the premixed microcombustion of hydrogen–air mixture
Authors: Jha Vikalp , Velidi Gurunadh , Emani Sampath
Published: May 2022

The premixed combustion of a lean hydrogen–air mixture is analyzed in this study to examine various properties and flame stabilization. A two‐dimensional (2D) analysis of a microscale combustor is performed with various shapes of bluff bodies (e.g., circular and triangular). Nine bluff bodies are placed at the entrance of the microscale combustor and solved with 2D governing equations. The analysis is performed with the three velocities of 10, 20, and 30 m/s, but the equivalence ratio is fixed in all cases. The various characteristics of the microscale combustor are studied such as the temperature of the wall, difference in peak temperature, the mean velocity at the outlet, and temperature of the exhaust gases. Flame stabilization depends on various factors such as bluff body shape and size, and the velocity of the fuel–air mixture at the inlet and recirculation zone. In comparison to all bluff body cases, we observe that the wall blade bluff body is the most efficient (low exhaust gas temperature, large recirculation zone, low mean velocity at the outlet of the microcombustor, and high wall temperature) compared with all eight other bluff body cases. Combustion efficiency is directly proportional to the wall temperature, meaning that the microcombustor with wall blade bluff bodies is more efficient with a stabilized flame. The simulation results are compared with published data on an L/D ratio of 15.
Study on the agricultural crop drought index based on weights of growth stages
Authors: Pei Wei , Fu Qiang , Ren Yongtai , Li Tianxiao
Published: May 2022

Drought is one of the main natural disasters affecting economic development and food security. Drought monitoring and identification are the premise of disaster risk management, and the drought index is the main means of monitoring and identifying drought. The paper proposes a new drought index, the agricultural crop drought index (ACDI), which is suitable for rainfed agriculture in arid areas. ACDI calculates water deficit from precipitation and evapotranspiration and considers the weight of crop growth stage. The weight of growth stage and water deficit constitute the weighted data series. The fitting distribution is optimized by Kolmogorov–Smirnov test, and the data are standardized to obtain ACDI. The weight of growth stage is determined by the multiple correlation coefficient between meteorological factors and grain yield. A large weight is equivalent to a large coefficient, large coefficient means that meteorological factors in this growth stage will have a greater impact on grain yield, so the water deficit in this growth stage should play a more important role in defining drought index to better identify agricultural drought from the perspective of crops. Finally, Qiqihar, a semiarid area in Northeast China, is selected as the research area for the case study. Comparing ACDI with standard precipitation index (SPI), standardized precipitation evapotranspiration index (SPEI) and crop water deficit index (CWDI), the standard deviation of ACDI is larger, which indicates that the difference between index values is larger and it is relatively good in distinguishing the degree of drought. In addition, the correlation coefficient between ACDI and climate grain yield passed the test with a significance level of 0.05, while the other three indexes did not pass the test, which shows that the relationship between ACDI and grain yield is higher than the other three drought indexes. For arid areas, grain yield can reflect the impact of drought. Therefore, ACDI looks more promising to identify agricultural drought from the perspective of crops. ACDI provides a reference for monitoring agricultural drought from the perspective of crop growth stage, and enriches the drought index theory.
Characterizing the landscape of cervical squamous cell carcinoma immune microenvironment by integrating the single‐cell transcriptomics and RNA‐Seq
Authors: Yin Ruiling , Zhai Xiuming , Han Hongyan , Tong Xuedong , Li Yan , Deng Kun
Published: May 2022

Background

Cervical squamous cell carcinoma (CSCC), caused by the infection of high‐risk human papillomavirus, is one of the most common malignancies in women worldwide.

Methods

RNA expression data, including those from the Cancer Genome Atlas, Gene Expression Omnibus, and Genotype‐Tissue Expression databases, were used to identify the expression of RNAs in normal and tumor tissue. Correlation analysis was performed to identify the immune‐related long noncoding RNAs (IRLs) and hypoxia‐related genes (IRHs) that can influence the activity of the immune system. Prognosis models of immune‐related RNAs (IRRs) were used to construct a coexpression network of the immune system. We identified the role of IRRs in immunotherapy by correlation analysis with immune checkpoint genes (ICGs). We then validated the expression data by integrating two single‐cell sequencing data sets of CSCC to identify the key immune features.

Results

In total, six immune‐related gene (IRG), four IRL, and five IRH signatures that can significantly influence the characteristics of the tumor immune microenvironment (TIME) were selected using machine learning methods. The expression level of ICGs was significantly upregulated in GZMB+CD8+ T‐cells and tumor‐associated macrophages (TAMs) in tumor tissues. TGFBI+ TAMs are a kind of blood‐derived monocyte‐derived M0‐like TAM linked to hypoxia and a poor prognosis. IFI30+ M1‐like TAMs participate in the process of immune‐regulation and showed a role in the promotion of CD8+ T‐cells and Type 1 T helper (Th1)/Th2 cells in the coexpression network, together with several IRLs, IRGs, and ICGs.

Conclusions

CD16+ monocyte‐derived IFI30+ TAMs participated in our coexpression network to regulate the TIME, showing the potential to be a novel immunotherapy target. The enrichment of M0‐like TAMs was associated with a worse prognosis in the high‐risk score group with IRH signatures. Remarkably, M0‐like TAMs in tumor tissues overexpressed TGFBI and were associated with several well‐known tumor‐proliferation pathways.
Groundwater modelling of a shallow aquifer for the assessment of water logging: A case study of the Cebala‐Borj Touil irrigation perimeter, northern Tunisia
Authors: Rzigui Houda , Bogacki Wolfgang , Hörmann Georg , Hachicha Mohamed
Published: May 2022

The Cebala‐Borj Touil (Cebala) Plain in Tunisia is a large perimeter with an area of 3,200 ha. In 1990, a drainage and irrigation system was installed. The groundwater system is complex due to the proximity to the sea, the low slope, and the low performance of natural drainage. It is characterized by shallow groundwater and soil water logging. The flooded area is controlled by natural and artificial factors. The natural parameters are the flat slope and the soil texture. The man‐made problems are caused by inappropriate irrigation and drainage deficiency. The numerical groundwater flow simulation model FEFLOW (Finite Element Subsurface Flow System) was used to simulate the groundwater depth variability. The calculated water table depth ranged from less than 0.5 m from the ground surface to more than 8 m. Based on the calibrated model, several management scenarios were investigated to study the possibilities to mitigate the problem of water logging in the perimeter. The model results showed that improving the drainage efficiency and reducing the irrigation amounts could solve the water logging problem, but not entirely. For the low flooded parts, a pumping option could be considered. The final management scheme might include the combination of all the tested management scenarios.
In vitro fungicide sensitivity of Clarireedia, Fusarium, and Microdochium isolates from grasses
Authors: Gagkaeva Tatiana , Orina Aleksandra , Gavrilova Olga , Usoltseva Marina , Crouch Jo Anne , Normann Karin , Entwistle Kate , Torp Torfinn , Espevig Tatsiana
Published: May 2022

Clarireedia spp., Fusarium culmorum, and Microdochium nivale are destructive and widespread fungal pathogens causing turfgrass disease. Chemical control is a key tool for managing these diseases on golf greens but are most effective when used in a manner that reduces overall inputs, maximizes fungicide efficacy, and minimizes the risk of fungicide resistance. In this study, sensitivity to eight commonly used fungicides was tested in 13 isolates of Clarireedia spp., F. culmorum, and M. nivale via in vitro toxicity assays. Fungicide sensitivity varied significantly among the three species, with isolates of F. culmorum showing the least sensitivity. The sensitivity of M. nivale to all tested fungicides was high (with the exception of tebuconazole), but only four fungicides (Banner Maxx®, Instrata® Elite, Medallion TL, and Switch® 62,5 WG) suppressed the growth of M. nivale completely at a concentration of 1% of the recommended dose. All three fludioxonil‐containing fungicides either alone (Medallion TL) or in combination with difeconazole (Instrata® Elite) or cyprodinil (Switch® 62,5 WG) had the same high efficacy against isolates of both M. nivale and Clarireedia spp. On average, the Clarireedia isolates tested in this study showed high sensitivity to the tested fungicides, except for Heritage (azoxystrobin). The observed variation in sensitivity among isolates within the same fungal species to different fungicides needs further investigation, as an analysis of the differences in fungal growth within each fungal group revealed a significant isolate × fungicide interaction (p < .001).
Nowcasting tail risk to economic activity at a weekly frequency
Authors: Carriero Andrea , Clark Todd E. , Marcellino Massimiliano
Published: May 2022

This paper focuses on nowcasts of tail risk to GDP growth, with a potentially wide array of monthly and weekly information used to produce nowcasts on a weekly basis. We consider Bayesian mixed frequency regressions with stochastic volatility and Bayesian quantile regressions. Our results show that, within some limits, more information helps the accuracy of nowcasts of tail risk to GDP growth. Accuracy typically improves as time moves forward within a quarter, making additional data available, with monthly data more important to accuracy than weekly data. Accuracy also typically improves with the use of financial indicators in addition to a base set of macroeconomic indicators.
Robust inference under time‐varying volatility: A real‐time evaluation of professional forecasters
Authors: Demetrescu Matei , Hanck Christoph , Kruse‐Becher Robinson
Published: May 2022

In many forecast evaluation applications, standard tests as well as tests allowing for time‐variation in relative forecast ability build on heteroskedasticity‐and‐autocorrelation consistent (HAC) covariance estimators. Yet, the finite‐sample performance of these asymptotics is often poor. “Fixed‐
” asymptotics, used to account for long‐run variance estimation, improve finite‐sample performance under homoskedasticity, but lose asymptotic pivotality under time‐varying volatility. Moreover, loss of pivotality due to time‐varying volatility is found in the standard HAC framework in certain cases as well. We prove a wild bootstrap implementation to restore asymptotically pivotal inference for the above and new CUSUM‐ and Cramér‐von Mises‐based tests in a fairly general setup, allowing for estimation uncertainty from either a rolling window or a recursive approach when fixed‐
asymptotics are adopted to achieve good finite‐sample performance. We then investigate the (time‐varying) performance of professional forecasters relative to naive no‐change and model‐based predictions in real‐time. We exploit the Survey of Professional Forecasters (SPF) database and analyze nowcasts and forecasts at different horizons for output and inflation. We find that not accounting for time‐varying volatility seriously affects outcomes of tests for equal forecast ability: wild bootstrap inference typically yields convincing evidence for advantages of the SPF, while tests using non‐robust critical values provide remarkably less. Moreover, we find significant evidence for time‐variation of relative forecast ability, the advantages of the SPF weakening considerably after the “Great Moderation.”
Linear ubiquitination modification of NR6A1 by LUBAC inhibits RIPK3 kinase activity and attenuates apoptosis of vascular smooth muscle cells
Authors: Cai Zhou , He Xin , Liu Shuai , Bai Yang , Pan Baihong , Wu Kemin
Published: May 2022

Nuclear receptor subfamily 6 group A member 1 (NR6A1) is involved in promoting the apoptotic process of vascular smooth muscle cells (VSMCs) which is a critical process involved in atherosclerosis, but the action mechanism remains to be determined. Therefore, we studied the underlying mechanisms by which NR6A1 accelerated VSMC apoptosis in atherosclerosis. An atherosclerosis model has been established in apolipoprotein E‐deficient rats with a high‐fat diet for 12 weeks, which was characterized by pathological aortic plaques, increased lipid deposition and collagen content in aortic tissues, and high cholesterol and triglycerides levels in the serum. NR6A1 was experimentally shown to increase at protein level rather than messenger RNA level in atherosclerotic rats. Immunofluorescence exhibited the main location of NR6A1 in the cell nucleus of rat aortic tissues. By performing ectopic expression experiments, NR6A1 was demonstrated to suppress the viability and expedite the apoptosis of VSMCs, corresponding to augmented caspase‐3, caspase‐8, and caspase‐9 activities. It was further unraveled that NR6A1 could activate receptor‐interacting serine/threonine‐protein kinase 3 (RIPK3) by inducing its phosphorylation. Conversely, RIPK3 inhibitor GSK872 undermined the proapoptotic effect of NR6A1 on VSMCs. The co‐immunoprecipitation assay identified that linear ubiquitin chain assembly complex (LUBAC) can be pulled down by NR6A1. Furthermore. LUBAC inhibited the expression of NR6A1 by promoting its linear ubiquitination, thereby dephosphorylating RIPK3 and consequently inhibiting the VSMC apoptosis. Overall, LUBAC‐induced linear ubiquitination of NR6A1 can potentially arrest the apoptosis of VSMCs in atherosclerosis by downregulating RIPK3 and attenuating caspase activity. This finding suggests promising athero‐protective targets by limiting VSMC apoptosis.
Simulation studies of polypeptoids using replica exchange with dynamical scaling and dihedral biasing
Authors: Raubenolt Bryan A. , Rick Steven W.
Published: May 2022

Polypeptoids differ from polypeptides in that the amide bond can more frequently adopt both cis and trans conformations. The transition between the two conformations requires overcoming a large energy barrier, making it difficult for conventional molecular simulations to adequately visit the cis and trans structures. A replica‐exchange method is presented that allows for easy rotations of the amide bond and also an efficient linking to a high temperature replica. The method allows for just three replicas (one at the temperature and Hamiltonian of interest, a second high temperature replica with a biased dihedral potential, and a third connecting them) to overcome the amide bond sampling problem and also enhance sampling for other coordinates. The results indicate that for short peptoid oligomers, the conformations can range from all cis to all trans with an average cis/trans ratio that depends on side chain and potential model.
Comparison of Race‐Based and Non–Race‐Based Equations for Kidney Function Estimation in Critically Ill Thai Patients for Vancomycin Dosing
Authors: Sitaruno Sirima , Santimaleeworagun Wichai , Pattharachayakul Sutthiporn , DeBacker Kenneth C. , Vattanavanit Veerapong , Binyala Wanrada , Pai Manjunath P.
Published: May 2022

Empiric antibiotic dosing frequently relies on an estimate of kidney function based on age, serum creatinine, sex, and race (on occasion). New non–race‐based estimated glomerular filtration rate (eGFR) equations have been published, but their role in supporting dosing is not known. Here, we report on a population pharmacokinetic model of vancomycin that serves as a useful probe substrate of eGFR in critically ill Thai patients. Data were obtained from medical records during a 10‐year period. A nonlinear mixed‐effects modeling approach was conducted to estimate vancomycin parameters. Data from 208 critically ill patients (58.2% men and 36.0% septic shock) with 398 vancomycin concentrations were collected. Twenty‐three covariates including 12 kidney function estimates were tested and ranked on the basis of the model performance. The median (min, max) age, weight, and serum creatinine was 69 (18, 97) years, 60.0 (27, 120) kg, and 1.53 (0.18, 7.15) mg/dL, respectively. The best base model was a 1‐compartment linear elimination with zero‐order input and proportional error model. A Thai‐specific eGFR equation not indexed to body surface area model best predicted vancomycin clearance (CL). The typical value for volume of distribution and CL was 67.5 L and 1.22 L/h, respectively. A loading dose of 2000 mg followed by maintenance dose regimens based on eGFR is suggested. The Thai GFR not indexed to BSA model best predicts vancomycin CL and dosing in the critically ill Thai population. A 5% to 10% absolute gain in the vancomycin probability of target attainment is expected with the use of this population‐specific eGFR equation.
Impact of prenatally diagnosed congenital heart defects on outcomes and management
Authors: Wong Jennifer , Kohari Katherine , Bahtiyar Mert Ozan , Copel Joshua
Published: May 2022

Fetal echocardiogram aids in prenatal identification of neonates at high risk for congenital heart defects (CHD). Prenatal detection rates for CHD have increased with improved ultrasound technology, the use of the early fetal echocardiography, and standardization of the performance of the fetal echocardiogram. Accurate prenatal detection of CHD, particularly complex CHD, is an important contributor to improved survival rates for patients with CHD. Early detection allows for families to choose whether or not to continue with pregnancy, referral to pediatric cardiology specialists for patient education, and delivery planning. Better psychosocial supports are needed for families with CHD.
Chronic fibrosing esophagitis with diffuse esophageal intramural pseudo‐diverticulosis
Authors: Hentschel Florian
Published: May 2022

Diffuse esophageal intramural pseudo‐diverticulosis (DEIPD) is a chronic fibrosing inflammation of the esophagus of unknown origin. Its name derives from the characteristic pseudo‐diverticula formed by dilated ducts of submucosal glands. With an assumed prevalence of approximately 5–50/100 000, DEIPD is more frequent than previously estimated. It preferentially affects men between 50 and 70 years of age with a history of alcohol and tobacco abuse. Key symptoms are chronic dysphagia and food impactions. Typical endoscopic findings are multiple small, longitudinally aligned pseudo‐diverticle openings and trachealization of the esophagus. Additionally, the usually gray mucosa may show a fine‐grained pattern of very small red dots that merge into a pink tint, called “faux uni pattern.” Once established, clinical symptoms and endoscopic changes persist throughout life. Although there is no known causal therapy, complications like bolus impactions, candida infections, or reflux can and should be treated.
Oral pre‐exposure prophylaxis preference, uptake, adherence and continuation among adolescent girls and young women in Kampala, Uganda: a prospective cohort study
Authors: Mayanja Yunia , Kamacooko Onesmus , Lunkuse Jane Frances , Muturi‐Kioi Vincent , Buzibye Allan , Omali Denis , Chinyenze Kundai , Kuteesa Monica , Kaleebu Pontiano , Price Matt A.
Published: May 2022

Introduction

Oral pre‐exposure prophylaxis (PrEP) has been scaled up; however, data from real‐world settings are limited. We studied oral PrEP preference, uptake, adherence and continuation among adolescent girls and young women (AGYW) vulnerable to HIV in sub‐Saharan Africa.

Methods

We conducted a prospective cohort study among 14‐ to 24‐year‐old AGYW without HIV who were followed for 12 months in Kampala, Uganda. Within at least 14 days of enrolment, they received two education sessions, including demonstrations on five biomedical interventions that are; available (oral PrEP), will be available soon (long‐acting injectable PrEP and anti‐retroviral vaginal ring) and in development (PrEP implant and HIV vaccine). Information included mode and frequency of delivery, potential side effects and method availability. Volunteers ranked interventions, 1 = most preferred to 5 = least preferred. Oral PrEP was “preferred” if ranked among the top two choices. All were offered oral PrEP, and determinants of uptake assessed using Poisson regression with robust error variance. Adherence was assessed using plasma tenofovir levels and self‐reports.

Results

Between January and October 2019, 532 volunteers were screened; 285 enrolled of whom 265 received two education sessions. Mean age was 20 years (SD±2.2), 92.8% reported paid sex, 20.4% reported ≥10 sexual partners in the past 3 months, 38.5% used hormonal contraceptives, 26.9% had chlamydia, gonorrhoea and/or active syphilis. Of 265 volunteers, 47.6% preferred oral PrEP. Willingness to take PrEP was 90.2%; however, uptake was 30.6% (n = 81). Following enrolment, 51.9% started PrEP on day 14 (same day PrEP offered), 20.9% within 30 days and 27.2% after 30 days. PrEP uptake was associated with more sexual partners in the past 3 months: 2–9 partners (aRR = 2.36, 95% CI: 1.20–4.63) and ≥10 partners (aRR 4.70, 95% CI 2.41–9.17); oral PrEP preference (aRR 1.53, 95% CI 1.08–2.19) and being separated (aRR 1.55, 95% CI 1.04–2.33). Of 100 samples from 49 volunteers during follow up, 19 had quantifiable tenofovir levels (>10 μg/L) of which only three were protective (>40 μg/L).

Conclusions

Half of AGYW preferred oral PrEP, uptake and adherence were low, uptake was associated with sexual behavioural risk and oral PrEP preference. Development of alternative biomedical products should be expedited to meet end‐user preferences and, community delivery promoted during restricted movement.
Research priorities for mitochondrial disorders: Current landscape and patient and professional views
Authors: Thomas Rhys H. , Hunter Amy , Butterworth Lyndsey , Feeney Catherine , Graves Tracey D. , Holmes Sarah , Hossain Pushpa , Lowndes Jo , Sharpe Jenny , Upadhyaya Sheela , Varhaug Kristin N. , Votruba Marcela , Wheeler Russell , Staley Kristina , Rahman Shamima
Published: May 2022

Primary mitochondrial disorders encompass a wide range of clinical presentations and a spectrum of severity. They currently lack effective disease‐modifying therapies and have a high mortality and morbidity rate. It is therefore essential to know that competitively funded research designed by academics meets the core needs of people with mitochondrial disorders and their clinicians. Priority setting partnerships are an established collaborative methodology that brings patients, carers and families, charity representatives and clinicians together to try to establish the most pressing and unanswered research priorities for a particular disease. We developed a web‐based questionnaire, requesting all patients affected by primary mitochondrial disease, their carers and clinicians to pose their research questions. This yielded 709 questions from 147 participants. These were grouped into overarching themes including basic biology, causation, health services, clinical management, social impacts, prognosis, prevention, symptoms, treatment and psychological impact. Following the removal of “answered questions”, the process resulted in a list of 42 discrete, answerable questions. This was further refined by web‐based ranking by the community to 24 questions. These were debated at a face‐to‐face workshop attended by a diverse range of patients, carers, charity representatives and clinicians to create a definitive “Top 10 of unanswered research questions for primary mitochondrial disorders”. These Top 10 questions related to understanding biological processes, including triggers of disease onset, mechanisms underlying progression and reasons for differential symptoms between individuals with identical genetic mutations; new treatments; biomarker discovery; psychological support and optimal management of stroke‐like episodes and fatigue.
Regional Analysis of Liver Surface Nodularity in a Single Axial MR Image for Staging Liver Fibrosis
Authors: Kim Tae‐Hoon , Kim Youe Ree , Jeong Chang‐Won , Kim Hyung Joong , Kim Jin Woong , Lee Young Hwan , Yoon Kwon‐Ha
Published: May 2022

Background

The assessment of liver surface nodularity (LSN) for staging hepatic fibrosis is restricted in clinical practice because it requires customized software and time‐consuming procedures. A simplified method to estimate LSN score may be useful in the clinic.

Purpose

To evaluate the regional analysis of LSN and processing time in a single axial liver MR image for staging liver fibrosis.

Study Type

Retrospective.

Population

A total of 210 subjects, a multicenter study.

Field Strength/Sequence

A 3 T/noncontrast gradient echo T1WI.

Assessment

Subjects were divided into five fibrosis groups (F0 = 29; F1 = 20; F2 = 32; F3 = 50; F4 = 79) based on the METAVIR fibrosis scoring system. The mean LSN (on three slices) and regional LSN (on one slice) measurements, and the processing times, are compared. The regional LSN scores in five regions‐of‐interests (ROI1‐5) were analyzed in a single axial MRI at the level of the hilum by two independent observers.

Statistical Tests

Regional variations in LSN scores were compared using ANOVA with Tukey test. Agreement between the mean and regional LSN measurements was evaluated using Pearson correlation coefficients (r) and Bland–Altman plots. The diagnostic performance of mean and regional LSN scores according to fibrosis stage was evaluated with the AUROC. A P value < 0.05 was considered statistically significant.

Results

Total processing time for a regional LSN measurement (3.6 min) was 75.5% less than that for mean LSN measurement (14.7 min). Mean LSN scores and all five regional LSN scores showed significant differences between fibrosis groups. Among regional LSN scores, ROI5 showed the highest AUROC (0.871 at cut‐off 1.12) for discriminating F0‐2 vs. F3‐4 and the best correlation with mean LSN score (r = 0.800, −0.07 limit of agreement).

Conclusion

Quantitative regional LSN measurement in a single axial MR image reduces processing time. Regional ROI5 LSN score might be useful for clinical decision‐making and for distinguishing the difference between early fibrosis (F0‐2) and advanced fibrosis (F3−4) in the liver.

Evidence Level

3

Technical Efficacy

Stage 2