bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased curative treatment is associated with decreased prostate cancer‐specific and overall mortality in senior adults with high‐risk prostate cancer; results from a national registry‐based cohort study
Authors: Aas Kirsti , Dorothea Fosså Sophie , Åge Myklebust Tor , Møller Bjørn , Kvåle Rune , Vlatkovic Ljiljana , Berge Viktor
Published: August 2020

Background

The association between curative treatment (CurTrt) and mortality in senior adults (≥70 years) with high‐risk prostate cancer (PCa) is poorly documented. In a population‐based cohort we report temporal trends in treatment and PCa‐specific mortality (PCSM), investigating the association between CurTrt and mortality in senior adults with high‐risk PCa, compared to findings in younger men (<70 years).

Methods

Observational study from the Cancer Registry of Norway. Patients with high‐risk PCa were stratified for three diagnostic periods (2005‐08, 2009‐12 and 2013‐16), age (<70, vs ≥70) and primary treatment (CurTrt: Radical prostatectomy (RP), Radiotherapy (RAD) vs no curative treatment (NoCurTrt)). Competing risk and Kaplan‐Meier methods estimated PCSM and overall mortality (OM), respectively. Multivariable logistic regression models estimated odds for CurTrt, and multivariable Fine Gray and Cox regression models evaluated the hazard ratios for PCSM and OM.

Results

Of 19 763 evaluable patients, 54% were aged ≥70 years. Senior adults had more unfavorable PCa characteristics than younger men. Across diagnostic periods, use of CurTrt increased from 15% to 51% in men aged ≥70 and 65% to 81% in men aged < 70 years. With median five years follow‐up, PCSM decreased in all patients (P < .05), in the third period restricted to senior adults. In all patients NoCurTrt was associated with three‐fold higher 5‐year PCSM and two‐fold higher OM compared to CurTrt.

Conclusions

In high‐risk PCa patients, increased use of CurTrt, greatest in senior men, was observed along with decreased PCSM and OM in both senior and younger adults. CurTrt should increasingly be considered in men ≥70 years.
Extended multiplicative signal correction to improve prediction accuracy of protein content in weathered sorghum grain samples
Authors: Peiris Kamaranga H. S. , Bean Scott R. , Jagadish S. V. Krishna
Published: August 2020

Background and objectives

Sorghum grains may be subjected to weathering damage in the field as naked grains on the panicle are exposed to adverse environmental conditions during grain development or dry down before harvest. A near infrared (NIR) protein calibration model did not work as expected for weathered grains. Extended multiplicative signal correction was tested as a preprocessing method for spectra to improve the prediction accuracy of the model when weathered grain samples are evaluated.

Findings

NIR spectra of weathered sorghum grain samples showed marked distortions with a higher apparent absorbance at lower wavelengths in the 950–1650 nm spectral range. A partial least squares calibration developed with sound grain samples using spectra preprocessed with multiplicative signal correction (MSC) predicted protein content of validation sample set of sound grains with a root mean square error of prediction (RMSEP) = 0.67% and coefficient of determination (r2) = 0.83. However, performance of this calibration model dropped with RMSEP = 13.14% and r2 = 0.04 when used to predict proteins in weathered grain samples. Introduction of weathered grain spectra to the calibration improved predictive performance with RMSEP = 0.92% and r2 = 0.69. Application of extended multiplicative scatter correction (EMSC) to preprocess the spectra of the calibration with weathered grain samples enhanced the prediction performance with RMSEP = 0.61% and r2 = 0.85.

Conclusions

Inclusion of weathered grain spectra in the calibration and preprocessing spectra with EMSC markedly improved the robustness of the sorghum protein calibration.

Significance and novelty

Sorghum breeders using NIR spectroscopy for evaluation of protein levels in sorghum breeding lines can get the weathered grain samples also analyzed for protein levels by using this method.
Management of a complex traumatic dental injury: Crown, crown‐root, and root fracture
Authors: Sanaei‐rad Parisa , Hajihassani Neda , Jamshidi Davoud
Published: August 2020

Dental trauma can result in different kinds of injuries based on the extent, direction, and location of the impact. Multidisciplinary management of traumatized teeth is critical for successful treatment and improvement of the prognosis.
Enzymatic Synthesis of Aliphatic Acyloins Catalyzed by Thermostable Transketolase
Authors: Casajus Hubert , Lagarde Aurélie , Leremboure Martin , De Dios Miguel Thomas , Nauton Lionel , Thery Vincent , Fessner Wolf‐Dieter , Duguet Nicolas , Charmantray Franck , Hecquet Laurence
Published: August 2020

The thermostable transketolase from Geobacillus stearothermophilus (TKgst) was successfully engineered for the synthesis of aliphatic acyloins with varying carbon backbone lengths (C5−C10) based on protein structure‐guided studies. Efficient TKgst variants were identified with enhanced activities for substrate combinations of aliphatic aldehydes as acceptors together with aliphatic pyruvate homologues as donors. The TKgst single variant L382F was able to catalyze efficiently the transfer of the ketol group from hydroxypyruvate on all targeted aliphatic aldehydes (C3−C8) to give the corresponding 1,3‐dihydroxy ketones with good yields and excellent enantioselectivity. The combination of the H102L/H474S mutation previously designed for the improved utilization of aliphatic pyruvate homologues together with a F435I exchange gave the new variant H102L/H474S/F435I, which is able to transfer the acyl goup of 2‐oxobutyrate and 2‐oxovalerate to aliphatic aldehydes, giving mono hydroxylated ketones.
Insights into the Suzuki‐Miyaura Reaction Catalyzed by Novel Pd−Carbene Complexes. Are Palladium−Tetra‐ carbene Entities the Key Active Species?
Authors: De Tovar Jonathan , Rataboul Franck , Djakovitch Laurent
Published: August 2020

The assumption that the real active species involved in the Suzuki‐Miyaura reaction are homogeneous, heterogeneous or both is often proposed. However a lack in the characterization of true catalytic entities and their monitoring makes assumptions somewhat elusive. Here, three families of palladium(II) complexes bearing bisNHC, bispyridyl and bisphosphine ligands were synthesized in order to get new insights into the formation of active species in the Suzuki‐Miyaura reaction. Their comparative catalytic study reveals that the nature of the ligands as well as their spacer lengths are pivotal parameters governing the performance. All complexes evolve to Pd NPs under reaction conditions, and an orthogonal behavior is observed for two bisNHC complexes that form homoleptic tetracarbene species. Notably, these species are presumably involved in a new catalytic modus operandi. This ligand‐controlled reactivity and the formation of tetracarbene species open new routes towards the design of novel cross‐coupling catalysts via the mastering of highly‐active catalytic species.
Immunotherapy‐based combination strategies for advanced urothelial cancer: A long quest
Authors: Khaki Ali Raza , Agarwal Neeraj , Pal Sumanta K. , Grivas Petros
Published: August 2020

Lay Summary

Despite longer survival with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD‐1)/programmed cell death–ligand 1 (PD‐L1), metastatic urothelial carcinoma remains lethal. There is an unmet need to further improve the efficacy of these agents.

In their phase 2 trial, Zhang et al. evaluated the combination of pembrolizumab (a PD‐1 inhibitor) plus acalabrutinib (a novel agent inhibiting an enzyme considered relevant to immunotherapy resistance) based on strong rationale but did not demonstrate clinical benefit compared with pembrolizumab alone.

Future trials that examine such promising rational combinations may be able to evaluate selected patients based on validated biomarkers to optimize benefit in an endless pursuit of personalizing therapies.
Breast imaging, breast surgery, and cancer genetics in the age of COVID‐19
Authors: Yin Kanhua , Singh Preeti , Drohan Brian , Hughes Kevin S.
Published: August 2020

Background

The objective of the current study was to provide insight into the effect of coronavirus disease 2019 (COVID‐19) on breast cancer screening, breast surgery, and genetics consultations.

Methods

User data from a risk assessment company were collected from February 2 to April 11, 2020. The use of risk assessment was used as a proxy for the use of 3 breast cancer services, namely, breast imaging, breast surgery, and genetics consultation. Changes in the use of these services during the study period were analyzed.

Results

All 3 services experienced significant declines after the COVID‐19 outbreak. The decline in breast surgery began during the week of March 8, followed by breast imaging and genetics consultation (both of which began during the week of March 15). Breast imaging experienced the most significant reduction, with an average weekly decline of 61.7% and a maximum decline of 94.6%. Breast surgery demonstrated an average weekly decline of 20.5%. When surgical consultation was stratified as breast cancer versus no breast cancer, the decrease among in non–breast cancer patients was more significant than that of patients with breast cancer (a decline of 66.8% vs 11.5% from the pre‐COVID average weekly volume for non–breast cancer patients and patients with breast cancer, respectively). During the week of April 5, use of genetics consultations dropped to 39.9% of the average weekly volumes before COVID‐19.

Conclusions

COVID‐19 has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment.
Trimetallic Nanoparticles Encapsulated into Bamboo‐Like N‐Doped Carbon Nanotubes as a Robust Catalyst for Efficient Oxygen Evolution Electrocatalysis
Authors: Lu Mengting , Li Yuwen , Wu Yuhang , Xu Hui , Gao Junkuo , Xu Shiqing
Published: August 2020

High‐efficiency oxygen evolution reaction (OER) electrocatalysts based on transition metal materials are one of the most promising alternatives, but their activity and durability are still far from desirable. Here, we report trimetallic N‐doped carbon nanotubes with rapid electron transport and rapid diffusion of the electrolyte that can significantly enhance the OER. The introduction of a third metal can adjust the electronic structure, thereby causing favorable intermediate adsorption on the catalysts. The optimized catalyst CoFeNi@CNTs exhibits a low overpotential of 287 mV at 10 mA cm−2 and a small Tafel slope of 32 mV dec−1, which are obviously superior to the precious catalyst IrO2 and most previously reported catalysts. The CoFeNi@CNTs also exhibit excellent OER stability with small current density decay after 12 h. The outstanding OER activity is ascribed to the unique carbon nanotube structure and strong synergy between three metals.
A multi‐illuminant synthetic image test set
Authors: Hao Xiangpeng , Funt Brian
Published: August 2020

A new multi‐illuminant synthetic image test set called MIST is described and made publicly available. MIST is intended primarily for evaluating illumination estimation and color constancy methods, but additional data are provided to make it useful for other computer vision applications as well. MIST addresses the problem found in most existing real‐image datasets, which is that the groundtruth illumination is only measured at a very limited number of locations, despite the fact that illumination tends to vary significantly in almost all scenes. In contrast, MIST provides for each pixel: (a) the percent surface spectral reflectance, (b) the spectrum of the incident illumination, (c) the separate specular and diffuse components of the reflected light, and (d) the depth (ie, camera‐to‐surface distance). The dataset contains 900 stereo pairs, each of the 1800 images being a 30‐band multispectral image covering the visible spectrum from 400 to 695 nm at a 5 nm interval. Standard sRGB versions of the multispectral images are also provided. The images are synthesized by extending the Blender Cycles ray‐tracing renderer. The rendering is done in a way that ensures the images are not only photorealistic, but physically accurate as well.
Nitrogen Fixation and Biological Behavior of Nanodiamond Colloidal Solutions
Authors: Kurakov Alexander V. , Batsanov Andrei S. , Gavrilkin Sergei M. , Batsanov Stepan S.
Published: August 2020

Detonation‐produced nanodiamond, both as a powder (with adsorbed water) and especially when suspended in an aqueous colloid, can support the growth (both aerobic and anaerobic) of bacteria and fungi. These were isolated and identified by microbiological methods, optical and electron microscopy, as species of Penicillium, Purpureocillium, Beaveria, Trichoderma and Aspergillus genera. The C : N molar ratio of the developing fibers (comprising fungal mycelia with attached bacteria and entrapped nanodiamond) decreased from 25 to 11 between the 1st and 10th week of incubation (cf. 40 in initial nanodiamond, 4.6 typical for bacteria and 8.3 for fungi), and from 4 to <1 after the 12th week, as the lysis of microorganisms releases carbon as CO2 and nitrogen as NH4+ or NO3−. The nitrogen content of the colloid increased by an order of magnitude and more, due to fixation of N2 by nanodiamond under ambient conditions.The process requires water but not necessarily oxygen present.
Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough
Authors: Mazzone Stuart B. , McGarvey Lorcan
Published: August 2020

Chronic cough, defined as a cough lasting > 8 weeks, is a common medical condition that exerts a substantial physical, mental, and social burden on patients. A subset of patients with chronic cough are troubled with a cough that persists despite optimal treatment of presumed associated common and uncommon conditions (refractory chronic cough; RCC) or in which no diagnosable cause for cough can be identified despite extensive assessment (unexplained chronic cough; UCC). Many of these patients exhibit clinical features of cough hypersensitivity, including laryngeal paresthesia, hypertussia, and allotussia. Over‐the‐counter cough remedies are ineffective and can lead to intolerable side effects when used for RCC/UCC, and the lack of approved treatments indicated for these conditions reflects a major unmet need. An increased understanding of the anatomy and neurophysiology of protective and pathologic cough has fostered a robust clinical development pipeline of several targeted therapies for RCC/UCC. This manuscript reviews the mechanisms presumed to underly RCC/UCC together with the rationale and clinical evidence for several targeted therapies currently under clinical investigation, including transient receptor potential channel antagonists, P2X3‐receptor antagonists, voltage‐gated sodium channel blockers, neuromodulators, and neurokinin‐1–receptor antagonists. Finally, we provide an overview of targets that have been investigated in preclinical models of cough and other airway diseases that may hold future promise for clinical studies in RCC/UCC. Development of targeted therapies with different sites of action may foster a precision medicine approach to treat this heterogeneous, underserved patient population.
Quantitative Systems Toxicology Modeling Predicts that Reduced Biliary Efflux Contributes to Tolvaptan Hepatotoxicity
Authors: Beaudoin James J. , Brock William J. , Watkins Paul B. , Brouwer Kim L. R.
Published: August 2020

Patients with autosomal dominant polycystic kidney disease (ADPKD) exhibit enhanced susceptibility to tolvaptan hepatotoxicity relative to other patient populations. In a rodent model of ADPKD, the expression and function of the biliary efflux transporter Mrp2 was reduced, and biliary excretion of a major tolvaptan metabolite (DM‐4103) was decreased. The current study investigated whether reduced biliary efflux could contribute to increased susceptibility to tolvaptan‐associated hepatotoxicity using a quantitative systems toxicology (QST) model (DILIsym). QST simulations revealed that decreased biliary excretion of DM‐4103, but not tolvaptan, resulted in substantial hepatic accumulation of bile acids, decreased electron transport chain activity, reduced hepatic adenosine triphosphate concentrations, and an increased incidence of hepatotoxicity. In vitro experiments (C‐DILI) with sandwich‐cultured human hepatocytes and HepaRG cells were performed to assess tolvaptan‐associated hepatotoxic effects when MRP2 was impaired by chemical inhibition (MK571, 50 µM) or genetic knockout, respectively. Tolvaptan (64 µM, 24‐hour) treatment of these cells increased cytotoxicity markers up to 27.9‐fold and 1.6‐fold, respectively, when MRP2 was impaired, indicating that MRP2 dysfunction may be involved in tolvaptan‐associated cytotoxicity. In conclusion, QST modeling supported the hypothesis that reduced biliary efflux of tolvaptan and/or DM‐4103 could account for increased susceptibility to tolvaptan‐associated hepatotoxicity; in vitro experiments implicated MRP2 dysfunction as a key factor in susceptibility. QST simulations revealed that DM‐4103 may contribute to hepatotoxicity more than the parent compound. ADPKD progression and gradual reduction in MRP2 activity may explain why acute liver events can occur well after one year of tolvaptan treatment.
Osteosarcoma pleural effusion: A diagnostic challenge with some cytologic hints
Authors: AbdullGaffar Badr
Published: August 2020

Pleural effusions can be the first manifestation, recurrence, or metastasis of small round cell sarcomas in children. The most common are Ewing sarcoma, neuroblastoma, and rhabdomyosarcoma. The cytomorphology is variable, the cells can be cohesive, single cells, small or large, morphologically mimicking lymphomas, carcinomas, melanomas, and mesothelioma depending on the sarcoma involved. Osteosarcomas are rare. Their rarity, variable histomorphologic features, immunophenotypic heterogeneity, being of osseous or extraosseous origin and focality of malignant osteoid matrix make their cytologic recognition a diagnostic challenge. They can be confused with small round cell sarcomas, may be misinterpreted as degenerative inflammatory cells, or masked by florid reactive mesothelial hyperplasia particularly in pleural effusions. However, attention to certain cytomorphologic features in smears and cellblock sections should raise suspicion. We report a case of a 9‐year‐old child who presented with cough, chest pain and breathing difficulty, left pleural effusion, a collapsed consolidated lower lung lobe, and a clinical impression of pneumonia. Pleural fluid cytology was initially reported as inflammatory effusion with florid reactive mesothelial hyperplasia. Tissue biopsy of the lung mass showed histomorphologic features consistent with osteosarcoma. A careful look at the cytology materials and cellblock sections showed helpful cytomorphologic features that were masked by florid reactive mesothelial cells and misinterpreted as degenerative inflammatory lymphocytes. An extracellular matrix was a helpful hint. Malignant pleural effusion secondary to osteosarcoma is rare. Cytologic examination may help reach the correct diagnosis if the smears and cellblock sections are carefully evaluated for certain helpful cytomorphologic features, particularly osteoid matrix.
Activation of the μ‐opioid receptor by alicyclic fentanyls: Changes from high potency full agonists to low potency partial agonists with increasing alicyclic substructure
Authors: Åstrand Anna , Vikingsson Svante , Jakobsen Ingrid , Björn Niclas , Kronstrand Robert , Gréen Henrik
Published: August 2020

Fentanyl analogs represent an important group of new psychoactive substances and knowing their efficacy and potency might assist in interpreting observed concentrations. The potency of fentanyl analogs can be estimated from in vitro studies and can be used to establish structure–activity relationships. In this study, recombinant CHO‐K1 cells (AequoScreen) expressing the human μ‐opioid receptor were used to establish dose–response curves via luminescent analysis for cyclopropyl‐, cyclobutyl‐, cyclopentyl‐, cyclohexyl‐, and 2,2,3,3‐tetramethylcyclopropylfentanyl (TMCPF), on three separate occasions, using eight different concentrations in an eight‐fold serial dilution in triplicates starting at ~60 μM. Fentanyl was used as a full agonist reference while morphine and buprenorphine were included for comparison. Cyclopropylfentanyl (EC50 = 4.3 nM), cyclobutylfentanyl (EC50 = 6.2 nM), and cyclopentylfentanyl (EC50 = 13 nM) were full agonists slightly less potent than fentanyl (EC50 = 1.7 nM). Cyclohexylfentanyl (EC50 = 3.1 μM, efficacy 48%) and TMCPF (EC50 = 1.5 μM, efficacy 65%) were partial agonists less potent than morphine (EC50 = 430 nM). Based on the results, cyclopropyl‐, cyclobutyl‐, and cyclopentylfentanyl would be expected to induce intoxication or cause fatal poisonings at similar concentrations to fentanyl, while the toxic or fatal concentrations of cyclohexylfentanyl and TMCPF would be expected to be much higher.
The frugivory network properties of a simplified ecosystem: Birds and plants in a Neotropical periurban park
Authors: Salazar‐Rivera Gabriela I. , Dáttilo Wesley , Castillo‐Campos Gonzalo , Flores‐Estévez Norma , Ramírez García Brenda , Ruelas Inzunza Ernesto
Published: August 2020

Frugivory networks exhibit a set of properties characterized by a number of network theory‐derived metrics. Their structures often form deterministic patterns that can be explained by the functional roles of interacting species. Although we know lots about how these networks are organized when ecosystems are in a complete, functional condition, we know much less about how incomplete and simplified networks (such as those found in urban and periurban parks) are organized, which features are maintained, which ones are not, and why. In this paper, we examine the properties of a network between frugivorous birds and plants in a small Neotropical periurban park. We found a frugivory network composed of 29 species of birds and 23 of plants. The main roles in this network are played by four species of generalist birds (three resident, one migratory: Myiozetetes similis, Turdus grayi, Chlorospingus flavopectus, and Dumetella carolinensis) and three species of plants (one exotic, two early successional: Phoenix canariensis, Phoradendron sp., and Witheringia stramoniifolia). When compared to reference data from other locations in the Neotropics, species richness is low, one important network‐level metric is maintained (modularity) whereas another one is not (nestedness). Nestedness, a metric associated with network specialists, is a feature this network lacks. Species‐level metrics such as degree, species strength, and module roles, are not maintained. Our work supports modularity as the most pervasive network‐level metric of altered habitats. From a successional point of view, our results suggest that properties revealed by species‐level indices may be developed at a later time, lagging the acquisition of structural elements.
Investigating population‐scale allelic differential expression in wild populations of Oithona similis (Cyclopoida, Claus, 1866)
Authors: Laso‐Jadart Romuald , Sugier Kevin , Petit Emmanuelle , Labadie Karine , Peterlongo Pierre , Ambroise Christophe , Wincker Patrick , Jamet Jean‐Louis , Madoui Mohammed‐Amin
Published: August 2020

Acclimation allowed by variation in gene or allele expression in natural populations is increasingly understood as a decisive mechanism, as much as adaptation, for species evolution. However, for small eukaryotic organisms, as species from zooplankton, classical methods face numerous challenges. Here, we propose the concept of allelic differential expression at the population‐scale (psADE) to investigate the variation in allele expression in natural populations. We developed a novel approach to detect psADE based on metagenomic and metatranscriptomic data from environmental samples. This approach was applied on the widespread marine copepod, Oithona similis, by combining samples collected during the Tara Oceans expedition (2009–2013) and de novo transcriptome assemblies. Among a total of 25,768 single nucleotide variants (SNVs) of O. similis, 572 (2.2%) were affected by psADE in at least one population (FDR < 0.05). The distribution of SNVs under psADE in different populations is significantly shaped by population genomic differentiation (Pearson r = 0.87, p = 5.6 × 10−30), supporting a partial genetic control of psADE. Moreover, a significant amount of SNVs (0.6%) were under both selection and psADE (p < .05), supporting the hypothesis that natural selection and psADE tends to impact common loci. Population‐scale allelic differential expression offers new insights into the gene regulation control in populations and its link with natural selection.
Meiofauna promotes litter decomposition in stream ecosystems depending on leaf species
Authors: Wang Fang , Lin Dunmei , Li Wei , Dou Pengpeng , Han Le , Huang Mingfen , Qian Shenhua , Yao Jingmei
Published: August 2020

Litter decomposition, a fundamental process of nutrient cycling and energy flow in freshwater ecosystems, is driven by a diverse array of decomposers. As an important component of the heterotrophic food web, meiofauna can provide a trophic link between leaf‐associated microbes (i.e., bacteria and fungi)/plant detritus and macroinvertebrates, though their contribution to litter decomposition is not well understood. To investigate the role of different decomposer communities in litter decomposition, especially meiofauna, we compared the litter decomposition of three leaf species with different lignin to nitrogen ratios in litter bags with different mesh sizes (0.05, 0.25, and 2 mm) in a forested stream, in China for 78 days. The meiofauna significantly enhanced the decomposition of leaves of high‐and medium‐ quality, while decreasing (negative effect) or increasing (positive effect) the fungal biomass and diversity. Macrofauna and meiofauna together contributed to the decomposition of low‐quality leaf species. The presence of meiofauna and macrofauna triggered different aspects of the microbial community, with their effects on litter decomposition varying as a function of leaf quality. This study reveals that the meiofauna increased the trophic complexity and modulated their interactions with microbes, highlighting the important yet underestimated role of meiofauna in detritus‐based ecosystems.
Carbon budget of the Harvard Forest Long‐Term Ecological Research site: pattern, process, and response to global change
Authors: Finzi Adrien C. , Giasson Marc‐André , Barker Plotkin Audrey A. , Aber John D. , Boose Emery R. , Davidson Eric A. , Dietze Michael C. , Ellison Aaron M. , Frey Serita D. , Goldman Evan , Keenan Trevor F. , Melillo Jerry M. , Munger J. William , Nadelhoffer Knute J. , Ollinger Scott V. , Orwig David A. , Pederson Neil , Richardson Andrew D. , Savage Kathleen , Tang Jianwu , Thompson Jonathan R. , Williams Christopher A. , Wofsy Steven C. , Zhou Zaixing , Foster David R.
Published: August 2020

How, where, and why carbon (C) moves into and out of an ecosystem through time are long‐standing questions in biogeochemistry. Here, we bring together hundreds of thousands of C‐cycle observations at the Harvard Forest in central Massachusetts, USA, a mid‐latitude landscape dominated by 80–120‐yr‐old closed‐canopy forests. These data answered four questions: (1) where and how much C is presently stored in dominant forest types; (2) what are current rates of C accrual and loss; (3) what biotic and abiotic factors contribute to variability in these rates; and (4) how has climate change affected the forest’s C cycle? Harvard Forest is an active C sink resulting from forest regrowth following land abandonment. Soil and tree biomass comprise nearly equal portions of existing C stocks. Net primary production (NPP) averaged 680–750 g C·m−2·yr−1; belowground NPP contributed 38–47% of the total, but with large uncertainty. Mineral soil C measured in the same inventory plots in 1992 and 2013 was too heterogeneous to detect change in soil‐C pools; however, radiocarbon data suggest a small but persistent sink of 10–30 g C·m−2·yr−1. Net ecosystem production (NEP) in hardwood stands averaged ~300 g C·m−2·yr−1. NEP in hemlock‐dominated forests averaged ~450 g C·m−2·yr−1until infestation by the hemlock woolly adelgid turned these stands into a net C source. Since 2000, NPP has increased by 26%. For the period 1992–2015, NEP increased 93%. The increase in mean annual temperature and growing season length alone accounted for ~30% of the increase in productivity. Interannual variations in GPP and NEP were also correlated with increases in red oak biomass, forest leaf area, and canopy‐scale light‐use efficiency. Compared to long‐term global change experiments at the Harvard Forest, the C sink in regrowing biomass equaled or exceeded C cycle modifications imposed by soil warming, N saturation, and hemlock removal. Results of this synthesis and comparison to simulation models suggest that forests across the region are likely to accrue C for decades to come but may be disrupted if the frequency or severity of biotic and abiotic disturbances increases.
Prioritizing symptom management in the treatment of chronic heart failure
Authors: Koshy Aaron O. , Gallivan Elisha R. , McGinlay Melanie , Straw Sam , Drozd Michael , Toms Anet G. , Gierula John , Cubbon Richard M. , Kearney Mark T. , Witte Klaus K.
Published: August 2020

Chronic heart failure (CHF) is a chronic, progressive disease that has detrimental consequences on a patient's quality of life (QoL). In part due to requirements for market access and licensing, the assessment of current and future treatments focuses on reducing mortality and hospitalizations. Few drugs are available principally for their symptomatic effect despite the fact that most patients' symptoms persist or worsen over time and an acceptance that the survival gains of modern therapies are mitigated by poorly controlled symptoms. Additional contributors to the failure to focus on symptoms could be the result of under‐reporting of symptoms by patients and carers and a reliance on insensitive symptomatic categories in which patients frequently remain despite additional therapies. Hence, formal symptom assessment tools, such as questionnaires, can be useful prompts to encourage more fidelity and reproducibility in the assessment of symptoms. This scoping review explores for the first time the assessment options and management of common symptoms in CHF with a focus on patient‐reported outcome tools. The integration of patient‐reported outcomes for symptom assessment into the routine of a CHF clinic could improve the monitoring of disease progression and QoL, especially following changes in treatment or intervention with a targeted symptom approach expected to improve QoL and patient outcomes.
CD8+ T cells are crucial for humoral immunity establishment by SA14‐14‐2 live attenuated Japanese encephalitis vaccine in mice
Authors: Kalia Anurag , Agrawal Mona , Gupta Nimesh
Published: August 2020

The live attenuated SA14‐14‐2 Japanese encephalitis (JE) vaccine is a historical vaccine that protects against JE. Despite its extensive use, the mechanism of protective immunity conferred by the SA14‐14‐2 vaccine is not well established. Here, we used mouse models to understand the mechanism of the development of humoral immunity against the vaccine. The vaccine induces robust GC responses within a week postimmunization. In lethal virus challenge, we show that CD4+ T cells alone, but not CD8+ T cells, are sufficient to confer vaccine‐mediated protection. However, the CD4‐mediated protection was potentiated in the presence of vaccine‐primed CD8+ T cells. Employing CD8‐deficient mice, we show that both the protective traits of CD4+ T cells and the quality of antibody response to the vaccine are impaired in absence of CD8+ T cells. We further demonstrate that the poor protective immune response induced by the vaccine in absence of CD8+ T cells is mainly due to the impaired differentiation and function of follicular Th cells, leading to suboptimal GC reaction. Our study highlights an unprecedented role of CD8+ T cells in the establishment of humoral responses to the vaccine. By elucidating underlying cellular determinants of vaccine‐induced protective immunity, our work has implications for rational design of vaccines against JE virus and related flaviviruses.
Influence of spectral acceleration correlation models on conditional mean spectra and probabilistic seismic hazard analysis
Authors: Rodríguez‐Castellanos Ali , Ruiz Sonia E. , Bojórquez Edén , Reyes‐Salazar Alfredo
Published: August 2020

Innovative engineering applications are proposed to satisfy the current necessities of earthquake engineering, which are well established from a conceptual perspective, and frequently, the development of some missing inputs is only required to employ them, such as the case of the correlations between spectral values at different vibration periods. Accordingly, we computed the correlation between spectral accelerations at two vibration periods using ground motions from interplate and, alternatively, intraslab events, recorded in firm ground of Mexico City. Results show that the spreading of correlation values depends on the rupture mechanism. Then, based on hypothesis test analyses, we used four correlation models available in the literature to predict our correlation values. According to the findings, we proposed a predictive correlation mathematical model for interplate and, separately, for intraslab seismic events. We evaluated the influence of the predictive correlation models on the results corresponding to two earthquake engineering applications. The first refers to compute conditional mean spectra and the second to perform probabilistic seismic hazard analysis (PSHA) using INp and, alternatively, Saavg, intensity measures. We found that while the conditional mean spectra might be affected in the region of short vibration periods, the computations of the PSHA with improved intensity measures are not affected significantly.
The pressure behind corporate social performance: Ownership and institutional configurations
Authors: Desender Kurt , Epure Mircea
Published: August 2020

Research summary

Drawing on the “varieties of capitalism” literature, we develop an actor‐centered framework that explains firm‐level corporate social performance (CSP) by emphasizing the importance of considering owners' and other stakeholders' motives toward CSP—which can be instrumental, relational or moral—and their salience in the national institutional setting. Results from an international panel show that investment company (government) ownership has a stronger negative (positive) relationship with CSP in liberal markets, in which owners are the key stakeholder, as compared to coordinated markets, which counterbalance the interests of multiple stakeholders. Family and company ownership have weaker links to CSP across institutional settings. We discuss implications for research and practice and argue that CSP policies may hold more relevance in liberal rather than coordinated market economies.

Managerial summary

Existing debates focus on the impact of corporate social performance (CSP) on firm outcomes. Less is known about the motives and pressures behind CSP, which may explain its variability across firms and institutional settings. We argue that powerful owners' motives are important for explaining CSP in liberal markets, where shareholders are the most important stakeholder, as compared to coordinated markets, which confer prominence to multiple stakeholders. Owners' motives are not homogenous and depending on the type of owners the link between ownership concentration and CSP can be negative (for investment companies) or positive (for governments). In coordinated markets, owners have a weaker impact on CSP, which is mostly attributable to their lower salience relative to stakeholders, rather than to a change in their motives.
Order aggressiveness and flash crashes
Authors: Rzayev Khaladdin , Ibikunle Gbenga
Published: August 2020

We present a novel framework illustrating the links between order aggressiveness and flash crashes. Our framework involves a trading sequence beginning with significant increases in aggressive sell orders relative to aggressive buy orders until instruments' prices fall to their lowest levels. Thereafter, a rise in aggressive buy orders propels prices back to their pre‐crash levels. Using a sample of S&P 500 stocks trading during the May 6, 2010, flash crash, we show that our framework is correctly specified and provide a basis for linking flash crashes to aggressive strategies, which are found to be more profitable during flash crashes.
Interest rate as the last link of chain during crisis
Authors: Kudar Alibey
Published: August 2020

In the literature, there are studies which conclude that interest rates have either positive or negative effect on exchange rates during financial crises in emerging markets. These results are in accordance with the traditional or revisionist views respectively. However, in the literature, there are also researches which result in interest rates not having influence on exchange rates, signalling that there might be an alternative to these two approaches. In this study, it is investigated whether interest rates can be cause of exchange rates by taking stock market into consideration and using the data of 2001 financial crisis in Turkey. In the analysis, ARDL co‐integration, VECM and Granger causality methods are applied and it is reached that the relationship was from stock market and exchange rates to interest rates, not vice versa.
Optimized parameters for the preparation of silk fibroin drug‐loaded microspheres based on the response surface method and a genetic algorithm–backpropagation neural network model
Authors: Zhang Xujing , Zhou Jianping , Xu Yan
Published: August 2020

Using silk fibroin as the base material, the drug‐loaded microspheres are prepared by an emulsification method. In order to determine the drug‐loading and drug‐release performance parameters of the microspheres, the central composite design method is used to design and investigate the effects of the parameters of the microsphere preparation process, such as the oil–water ratio, stirring temperature, and stirring rate, on the microsphere particle size, drug‐loading rate, and drug release rate. The “overall desirability” is taken as a comprehensive evaluation index, and the response surface method (RSM) and genetic algorithm–backpropagation (GA–BP) neural network GA–BP model are used to predict and evaluate the parameters of the drug‐loaded microsphere preparation process. The root‐mean‐square error values obtained from the RSM and BP–GA model experiments are 0.000325 and 0.00022, respectively. The results show that the BP–GA model has better prediction accuracy and optimization ability than the RSM. The optimal microsphere preparation process conditions were determined to be as follows: a water–oil ratio of 10:1, at a temperature of 45°C with stirring at a speed of 400 rpm, the particle size of the microspheres is 1.392 μm, the drug‐loading rate is 3.218%, and the drug release rate is 51.991%. The results of this study indicate that this approach is an effective method for the optimization of the parameters of the drug‐loaded microsphere preparation process.
Satellite cell self‐renewal in endurance exercise is mediated by inhibition of mitochondrial oxygen consumption
Authors: Abreu Phablo , Kowaltowski Alicia J.
Published: August 2020

Background

Skeletal muscle stem cells (satellite cells) are well known to participate in regeneration and maintenance of the tissue over time. Studies have shown increases in the number of satellite cells after exercise, but their functional role in endurance training remains unexplored.

Methods

Young adult mice were submitted to endurance exercise training and the function, differentiation, and metabolic characteristics of satellite cells were investigated in vivo and in vitro.

Results

We found that injured muscles from endurance‐exercised mice display improved regenerative capacity, demonstrated through higher densities of newly formed myofibres compared with controls (evidenced by an increase in embryonic myosin heavy chain expression), as well as lower inflammation (evidenced by quantifying CD68‐marked macrophages), and reduced fibrosis. Enhanced myogenic function was accompanied by an increased fraction of satellite cells expressing self‐renewal markers, while control satellite cells had morphologies suggestive of early differentiation. The beneficial effects of endurance exercise were associated with satellite cell metabolic reprogramming, including reduced mitochondrial respiration (O2 consumption) under resting conditions (absence of muscle injury) and increased stemness. During proliferation or activated states (3 days after injury), O2 consumption was equal in control and exercised cells, while exercise enhanced myogenic colony formation. Surprisingly, inhibition of mitochondrial O2 consumption was sufficient to enhance muscle stem cell self‐renewal characteristics in vitro. Moreover, transplanted muscle satellite cells from exercised mice or cells with reduced mitochondrial respiration promoted a significant reduction in inflammation compared with controls.

Conclusions

Our results indicate that endurance exercise promotes self‐renewal and inhibits differentiation in satellite cells, an effect promoted by metabolic reprogramming and respiratory inhibition, which is associated with a more favourable muscular response to injury.
Inhibition of cyclin‐dependent kinase 9 synergistically enhances venetoclax activity in mantle cell lymphoma
Authors: Zhao Xiaoxian , Bodo Juraj , Chen Ruoying , Durkin Lisa , Souers Andrew J. , Phillips Darren C. , Hsi Eric D.
Published: August 2020

Mantle cell lymphoma (MCL) is an aggressive and largely incurable subtype of non‐Hodgkin's lymphoma. Venetoclax has demonstrated efficacy in MCL patients with relapsed or refractory disease, however response is variable and less durable than CLL. This may be the result of co‐expression of other anti‐apoptotic proteins such as MCL‐1, which is associated with both intrinsic and acquired resistance to venetoclax in B‐cell malignancies. One strategy for neutralizing MCL‐1 and other short‐lived survival factors is to inhibit CDK9, which plays a key role in transcription. Here, we report the response of MCL cell lines and primary patient samples to the combination of venetoclax and novel CDK9 inhibitors. Primary samples represented de novo patients and relapsed disease, including relapse after ibrutinib failure. Despite the diverse responses to each single agent, possibly due to variable expression of the BCL‐2 family members, venetoclax plus CDK9 inhibitors synergistically induced apoptosis in MCL cells. The synergistic effect was also confirmed via venetoclax plus a direct MCL‐1 inhibitor. Murine xenograft studies demonstrated potent in vivo efficacy of venetoclax plus CDK9 inhibitor that was superior to each agent alone. Together, this study supports clinical investigation of this combination in MCL, including in patients who have progressed on ibrutinib.
One‐pot homo‐ and cross‐coupling of diazanaphthalenes via C‐H substitution: Synthesis of Bis‐ and Tris‐diazanaphthalenes
Authors: Ucar Sefa , Dastan Arif
Published: August 2020

The transition metal‐free coupling reactions of unactivated diazanaphthalenes were studied using only lithium tetramethylpiperidine (LiTMP) reagent. Symmetrical and nonsymmetrical bis‐diazanaphthalenes were synthesized in moderate to high yield by homo‐ and cross‐coupling of related monomers. In addition, the single‐step synthesis of diquinoxalino [2,3‐a: 2', 3'c] phenazine and 2,2': 3', 2″ ‐ terquinoxaline using the appropriate equivalent amount of LiTMP was performed. The products were characterized by means of NMR spectroscopy and HRMS spectrometry.
An Insight View on Synthetic Protocol, Surface Activity, and Biological Aspects of Novel Biocompatible Quaternary Ammonium Cationic Gemini Surfactants
Authors: Akram Mohd , Lal Hira , Osama Mohammad , Ansari Farah , Anwar Sana , Kabir‐ud‐Din  , Ahmad Ajaz , Samreen  , Azum Naved , Marwani Hadi M. , Asiri Abdullah M.
Published: August 2020

In this study, we prepared a novel series of diester‐functionalized cationic gemini surfactants (Cm‐E2O2‐Cm) containing ethylene oxide as a spacer with varying alkyl chain lengths and characterized by 1H NMR, FT‐IR, elemental analysis, and ESI‐MS. The physicochemical properties of the geminis were explored by tensiometry, fluorescence, dye solubilization, and Krafft point. These geminis acquire superior surface activity than the conventional surfactants. Fluorescence spectroscopy analysis affirmed that the micropolarity and aggregation number of micelles diminished with increase in the alkyl chain length. These geminis represent a new group of amphiphiles of considerably high biodegradability, better cleavability, and low toxicity as assessed by BOD test, FT‐IR analysis, and HC50 analysis, respectively. They also showed significant level of antimicrobial activity toward some specified bacterial strains of Gram‐positive and Gram‐negative by using agar well diffusion method. Furthermore, the thermogravimetric analysis provided information regarding thermal stabilities of the newly synthesized gemini surfactants.
Yield prediction with machine learning algorithms and satellite images
Authors: Sharifi Alireza
Published: August 2020

BACKGROUND

Barley is one of the strategic agricultural products available in the world, and yield prediction is important for ensuring food security. One way of estimating a product is to use remote sensing data in conjunction with field data and meteorological data. One of the main issues surrounding this comprises the use of machine learning techniques to create a multi‐resource data‐based estimation model. Many studies have been conducted on barley yield prediction from planting to harvest. Still, the effect of different time intervals on yield prediction has not been investigated. Furthermore, the effect of different periods on yield prediction has not been investigated.

RESULTS

In the present study, the whole growth period was divided into three parts. Using one of the major barley production areas in Iran, the performance of the proposed model was evaluated. In the first step, a model for integrating field data, remote sensing data and meteorological data was prepared. The results obtained show that, among the four machine learning methods implemented, the gaussian process regression algorithm performed best and estimated yield with r2 = 0.84, root mean square error = 737 kg ha−1 and mean absolute = 650 kg ha−1, 1 month before harvest.

CONCLUSION

It was found that the estimation results change depending on different agricultural zones and temporal training settings. The findings of the present study provide a powerful potential tool for the yield prediction of barley using multi‐source data and machine learning. © 2020 Society of Chemical Industry