bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic identification of activity cliffs with dual‐atom replacements and their rationalization on the basis of single‐atom replacement analogs and X‐ray structures
Authors: Hu Huabin , Bajorath Jürgen 
Published: November 2021

AbstractVery small chemical changes in active compounds causing large potency effects are of particular interest in medicinal chemistry and drug design. We have systematically searched active compounds with available high‐confidence activity data for pairs of structural analogs with dual‐atom replacements and additional analogs with corresponding single‐atom replacements. From ~287,000 unique qualifying compounds with activity against nearly 1900 unique targets, ~3500 target‐based analog pairs with dual‐atom replacements were identified. These included 852 pairs with significant differences in compound potency, representing a set of previously unobserved activity cliffs. Comparing these pairs with corresponding single‐atom replacement analogs, which were frequently identified, made it possible to systematically analyze how potency changes propagated from single‐ to dual‐atom replacements. The analysis uncovered different potency effects and revealed that individual atom replacements were often decisive for activity cliff formation. For a limited number of activity cliffs, X‐ray structures of targets in complex with cliff compounds were available, which aided in rationalizing potency alterations among analogs with single‐ or dual‐atom replacements. The analog pairs identified herein provide a rich resource of structure‐activity relationship information and attractive test cases for calibrating computational methods.
Microbial profiles of peri‐implant mucositis and peri‐implantitis: Submucosal microbial dysbiosis correlates with disease severity
Authors: Shi Yitian , Tong Zian , Zhang Yu , Si Misi , He Fuming 
Published: November 2021

AbstractObjectiveTo investigate the microbiome characteristics of peri‐implant mucositis (PM) and peri‐implantitis (PI), and to analyse the correlation between disease severity and submucosal microbial dysbiosis.Materials and MethodsA cross‐sectional study design was conducted. Submucosal biofilm samples from 27 PM sites and 37 PI sites from 64 patients were collected and analysed using 16S rRNA gene sequencing (Illumina). Differences in microbiological profiles between PM and PI were evaluated using the α‐diversity, β‐diversity and linear discriminant analysis effect size (LEfSe) analysis. The relative abundances of the taxa at the phylum and genus levels were compared using the Wilcoxon rank test and logistic regression. The microbial dysbiosis index (MDI) was calculated, and its relationship with clinical measurements (probing depth, bleeding on probing and marginal bone loss, among others) was analysed using Pearson's correlation coefficient.ResultsThe overall microbiome distribution in the PM and PI sites was similar according to α‐ and β‐diversity. Twenty‐three taxa at the genus level and two taxa at the phylum level showed significant differences in relative abundance between the two clinical classifications. Five taxa at the genus level were screened out for the MDI calculation after logistic regression. No clinical measurements but marginal bone loss showed a significant positive correlation with microbial dysbiosis.ConclusionThe microbiome richness, diversity and distribution were similar in PM and PI sites, including both common periodontal bacteria and novel species. In addition, an increase in marginal bone loss was significantly associated with submucosal microbial dysbiosis.
Assessment of the knowledge ofcanalis sinuosusamongst dentists and dental students: An online‐based cross‐sectional study
Authors: Lopes‐Santos Gabriela , Salzedas Leda Maria Pescinini , Bernabé Daniel Galera , Ikuta Carla Renata Sanomiya , Miyahara Glauco Issamu , Tjioe Kellen Cristine 
Published: November 2021

AbstractIntroductionCanalis sinuosus(CS) is a neurovascular canal that corresponds to a small branch of the infraorbital canal. This study aimed at assessing the knowledge and detection performance of CS amongst dentists and dental students.Materials and MethodsFour‐hundred and five dentists and dental students answered a questionnaire with three parts: 1. Socio‐demographical; 2. Clinical cases with cone‐ beam computed tomography (CBCT) sections showing CS and 3. Previous knowledge about CS. The chi‐squared test and Spearman's correlation test were used to compare results as appropriate.p‐values below .05 were considered statistically significant.ResultsMost participants did not identify CS in any CBCT. There was an association between the number of correct answers and dental specialties. Most individuals had not learned about CS previously. There was an association between past knowledge of CS and gender, highest academic degree, working environment, dental specialty and number of correct answers but not with age or experience in Dentistry.ConclusionThis study suggests that most dentists are not aware about CS and do not know how to diagnose it. Previous knowledge about CS positively influenced its identification in CBCT.
Effect of mutation supply on population dynamics and trait evolution in an experimental microbial community
Authors: Cairns Johannes , Jousset Alexandre , Becks Lutz , Hiltunen Teppo 
Published: November 2021

AbstractMutation supply can influence evolutionary and thereby ecological dynamics in important ways which have received little attention. Mutation supply influences features of population genetics, such as the pool of adaptive mutations, evolutionary pathways and importance of processes, such as clonal interference. The resultant trait evolutionary dynamics, in turn, can alter population size and species interactions. However, controlled experiments testing for the importance of mutation supply on rapid adaptation and thereby population and community dynamics have primarily been restricted to the first of these aspects. To close this knowledge gap, we performed a serial passage experiment with wild‐type Pseudomonas fluorescens and a mutant with reduced mutation rate. Bacteria were grown at two resource levels in combination with the presence of a ciliate predator. A higher mutation supply enabled faster adaptation to the low‐resource environment and anti‐predatory defence. This was associated with higher population size at the ecological level and better access to high‐recurrence mutational targets at the genomic level with higher mutation supply. In contrast, mutation rate did not affect growth under high‐resource level. Our results demonstrate that intrinsic mutation rate influences population dynamics and trait evolution particularly when population size is constrained by extrinsic conditions.
COVID‐19 vaccine take‐up rate and safety in adults with epilepsy: Data from a multicenter study in China
Authors: Lu Lu , Zhang Qi , Xiao Jing , Zhang Yingying , Peng Wei , Han Xiong , Chen Shengli , Yang Dan , Sander Josemir W. , Zhou Dong , Xiong Weixi 
Published: November 2021

SummaryObjectiveThis study was undertaken to investigate the COVID‐19 vaccine uptake rate and possible postvaccination effects in adults with epilepsy.MethodsWe invited adults with epilepsy attending three centers in China from July 24 to August 31, 2021 to participate in this study. We also asked age‐ and sex‐matched controls among people attending for other chronic neuropsychiatric conditions and healthy controls accompanying people with illness attending the hospitals to participate. We excluded people who, under the national guidelines, had evident contradictions to vaccination. Participants were interviewed face‐to‐face using questionnaires. Vaccine uptake and postvaccine adverse events among the people with epilepsy were compared with those with neuropsychiatric conditions and controls. We also compared the willingness and reasons for hesitancy among unvaccinated participants.ResultsWe enrolled 981 people, of whom 491 had epilepsy, 217 had other neuropsychiatric conditions, and 273 were controls. Forty‐two percent of those with epilepsy had had the first dose of a vaccine, compared with 93% of controls and 84% of the people with neuropsychiatric conditions (p < .0001). The majority (93.8%) of those immunized had inactivated vaccines. Among the unvaccinated people with epilepsy, 59.6% were willing to have the vaccine. Their main reasons for hesitation were potential adverse effects (53.3%) and concerns about losing seizure control (47.0%). The incidence of adverse events in the epilepsy group was similar to controls. Nineteen people with epilepsy reported an increase in seizure frequency. No episode of status epilepticus or prolonged seizures was reported. Two controls had their first‐ever seizure, which was unlikely related to the vaccine.SignificanceThe vaccine uptake rate in people with epilepsy was lower than in their same‐age controls. The postvaccination effect was no higher than in controls. We found no evidence suggesting worsening seizures after vaccination. Measurement and education focused on increasing the vaccination rate in epilepsy are warranted.
Climate and conspecific density inform phenotypic forecasting of juvenile Pacific salmon body size
Authors: Ulaski Marta E. , Finkle Heather , Beaudreau Anne H. , Westley Peter A. H. 
Published: November 2021

Abstract

Predicting effects of climate on fitness‐linked phenotypic traits, such as body size, is important for the management and conservation of species in the face of global change. During sensitive life stages, small changes in mean trait values can have large effects on survival and population productivity.

The transition from freshwater to saltwater by migrating anadromous fishes such as Pacific salmon (genus Oncorhynchus) is a critical life history transition, where survival is mediated by the size of migrating individuals. For salmon that spend extended periods rearing in freshwater, the size at ocean entry (i.e., smolt length) may be sensitive to changes in freshwater conditions shaped by biotic and abiotic factors, yet long‐term phenotypic time series for exploring these responses are rare.

We reconstructed a four‐decade time series of smolt length from archives of returning adult scales to quantify population‐specific responses to climate and conspecific density in a small watershed.

Dynamic linear modeling found that the relationship between a proxy for cohort density and smolt length at ocean entry was consistently negative, suggestive of competition. In contrast, there was a positive, yet dynamic, relationship between a proxy for density of emerging fry during the second summer of growth and smolt length.

The effect of temperature on smolt length was not consistent between two populations of sockeye salmon O. nerka that likely use distinct habitats within the watershed. A positive relationship between smolt length and temperature was only detected for the less abundant, early returning population.

Predictions of smolt length showed variable responses under scenarios of increasing temperature and high and low densities of conspecifics. Collectively, these results reveal population‐specific responses to temperature and density, suggesting that local habitat conditions may filter larger‐scale climate drivers.
Divergent fate of coccolithophores in a warming tropical ecosystem
Authors: Frada Miguel José , Keuter Sabine , Koplovitz Gil , Avrahami Yoav 
Published: November 2021

AbstractRising ocean temperatures will alter the diversity of marine phytoplankton communities, likely leading to modifications in food‐web and biogeochemical dynamics. Here we focus on coccolithophores, a prominent group of calcifying phytoplankton that plays a central role in the global carbon cycle. Using both new (2017–2020) and historical (1975–1976) data from the northern Red Sea, we found that during ‘mild summers’, the most common coccolithophores ‐ Emiliania huxleyi and Gephyrocapsa ericsonii ‐ co‐exist at similar densities. Both species then particularly flourish during subsequent winter periods where nutrient availability is higher due to convective mixing. However, during ‘hot summers’, which have become progressively the norm over the last decades with average surface temperatures exceeding 27°C for long time‐periods, G. ericsonii density markedly declined. Moreover, G. ericsonii remains at low background levels even during winter mixing periods, while E. huxleyi succession and development during winter appears unchanged. Further incubation assays using native assemblages confirmed that G. ericsonii’s growth over 27°C is significantly reduced relative to E. huxleyi. Additional factors likely contribute to impair G. ericsonii populations at sea, but temperature is a key factor. Our results illustrate the divergent impact of ongoing ocean warming in tropical phytoplankton species.
Capital Structure and Leverage in Private Equity Buyouts
Authors: Brown Greg , Harris Robert , Munday Shawn 
Published: November 2021

Private equity capital structures have evolved over time as financial markets and PE firms have created new ways to attract debt capital. In addition to borrowing by individual portfolio companies, debt is being backed by the fund or the general partner, producing different incentive and risk‐sharing features.The use of leverage has been a central feature of the PE model by, first of all, making possible a concentrated ownership position. Studies show that this model has created value for investors and can improve management of the underlying assets. What's more, PE's demonstrated effectiveness in reducing the potential costs of financial distress created by leverage is viewed as evidence of its “comparative advantage” in managing high leverage—one that effectively enables PE‐backed firms to take on higher levels of debt than comparable public companies. Nevertheless, PE structures have the potential to introduce agency conflicts of interests and incentives between GPs and LPs that may be managed with only partial success through contractual arrangements.The outcomes of capital structure decisions in PE vary considerably across the cycle, with rises and falls in leverage and concomitant changes in investment and returns. A number of studies offer explanations of the highly cyclical nature of private equity activity, suggesting that institutional features combined with macroeconomic cycles are to some degree “hardwired” into the industry.In providing evidence of continuing PE outperformance of public companies, the authors also show that the relationship between debt and performance depends on how leverage is measured. When debt is measured as a percentage of deal value, higher leverage is associated with higher average returns, reflecting the positive risk‐return trade‐off that basic finance theory would predict. But when leverage is measured as a multiple of EBITDA—as industry practitioners tend to do—the relationship with performance is weak and negative, suggesting that companies with high debt‐to‐value ratios are more likely to be mature “value” firms, whereas companies with high leverage ratios tilt towards “growth.”
Associations between dietary intake of total protein and sources of protein (plant vs. animal) and risk of all‐cause and cause‐specific mortality in older Australian men: The Concord Health and Ageing in Men Project
Authors: Das Arpita , Cumming Robert , Naganathan Vasikaran , Blyth Fiona , Couteur David G. Le , Handelsman David J. , Waite Louise M. , Ribeiro Rosilene V. R. , Simpson Stephen J. , Hirani Vasant 
Published: November 2021

AbstractBackgroundThe association between dietary protein intake and the risk of mortality is still controversial. The present study aimed to examine the associations between dietary total, animal and plant protein intake and all‐cause and cause‐specific mortality.MethodsCommunity‐dwelling men aged ≥ 70 years were recruited from local government areas surrounding Concord Hospital in Sydney, New South Wales for the Concord Health and Ageing in Men Project (CHAMP). The research dietitian administered a standardised validated diet history questionnaire to capture baseline dietary intake. In total, 794 men participated in a detailed diet history interview at the third wave. Adequacy of protein intake was assessed by comparing participant intake with the Nutrient Reference Values. Total protein intake was categorised into quintiles. Sources of protein were also captured. Mortality was ascertained through the New South Wales death registry. Cox proportional hazard models were used to assess the association between dietary total, animal and plant protein intake and risk of mortality.ResultsThe mean age of the CHAMP men was 81 years. In total, 162 men died during a median follow‐up of 3.7 years. Of these, 54 (33.3%) and 49 (30.2%) men died due to cancer and cardiovascular disease, respectively. There were U‐shaped associations between protein intake and all‐cause and cancer mortality. In multiple adjusted analysis, the second (hazard ratio [HR] = 0.38; 95% confidence interval [CI] = 0.18–0.82) and third (HR = 0.36; 95% CI = 0.16–0.82) quintiles of protein intakes were significantly associated with reduced risk of all‐cause and only second quintile (HR = 0.47; 95% CI = 0.10–0.93) of protein intake was significantly associated with cancer mortality. Each serve increase in animal protein was significantly associated with 12% (HR = 1.12; 95% CI = 1.00–1.26) and 23% (HR = 1.23; 95% CI = 1.02–1.49) increased risk of all‐cause mortality and cancer mortality respectively. Conversely, each serve increase in plant protein intake was significantly associated with 25% (HR = 0.75; 95% CI 0.61–0.92) and 28% (HR = 0.72; 95% CI = 0.53–0.97) reduced risk of all‐cause and cancer mortality, respectively. No such associations were observed for cardiovascular disease mortality.ConclusionsBoth second and third quintiles of total protein intake were associated with reduced all‐cause and cancer mortality. Plant protein was inversely associated with all‐cause and cancer mortality, whereas animal protein intake was positively associated with mortality.
Improvement of urban eye skin in Chinese female by supramolecular retinol plus acmella oleracea extract‐containing product
Authors: Ye Ying , Li Yanan , Bi Tianyu , Jiang Ligang 
Published: November 2021

AbstractBackgroundStudies on the anti‐wrinkle effects of retinol have been widely reported, but there are few reports on the infraorbital dark circles reducing effects.ObjectiveTo evaluate the efficiency and tolerance of one novel formulation containing supramolecular retinol plus acmella oleracea extract in Chinese urban eye skin.MethodsThirty‐three women with dark circles and visible fine wrinkles around the eyes, aged 20–45 years, were enrolled and instructed to use the formula for 6 weeks. Instrumental measures and subject assessment were obtained at baseline and at 3‐week intervals.ResultsAfter 6 weeks, Mexameter MX18 results demonstrated a statistically significant 13.8% decrease in MI (melanin index) value, and Colorimeter CL400 results demonstrated a statistically significant 0.5% increase in L* (lightness) value, which proved the efficacy of reducing dark circles. Primos‐Lite data showed that the wrinkles parameters of Ra, the wrinkle area %, and number of the wrinkles under the eyes and crow's feet revealed significant reduction to varying degrees. Cutometer results showed that R2 value increased significantly by 13.0%, indicating the benefits of firmer skin. In addition, subject assessment revealed that at the end of 6 weeks, the eye skin was noticeably improved.ConclusionsBy clinical evaluation and subject assessment, the novel formulation containing supramolecular retinol plus acmella oleracea extract can effectively diminish the collective signs of stressed urban eye skin for Chinese female in terms of dark circles, fine wrinkles, and sagging skin with good tolerance.
Do Younger Children Benefit More From Cognitive and Academic Interventions? How Training Studies Can Provide Insights Into Developmental Changes in Plasticity
Authors: Park Anne T. , Mackey Allyson P. 
Published: November 2021

ABSTRACTEducational interventions are frequently designed to occur during early childhood, based on the idea that earlier intervention will have greater long‐term academic benefits. However, surprisingly little is known about when cognitive and academic skills are most plastic, or malleable, during development. One way to study plasticity is to ask whether learning from targeted practice varies as a function of age. In this review, we summarize behavioral and neuroimaging studies that have tested for age‐related differences in cognitive training gains, for executive functions, and for academic skills (reading and math). Findings are mixed, with no clear evidence for an overall younger age benefit. We discuss current challenges and opportunities for leveraging research on cognitive and brain plasticity to inform the timing and content of early academic interventions.
Partitive Articles and Indefinites, Micro and Macrovariation
Authors: Pinzin Francesco , Poletto Cecilia 
Published: November 2021

AbstractThis introductory paper provides an overview of the main phenomena investigated in this Special Issue, such as the relation between the encoding of indefinites and the presence of genitive and definite markers, the relation between partitivity and indefiniteness and the distribution of these phenomena in minority, or “micro”, varieties – such as Italian dialects, Galloromance varieties, North and South Saami – compared to the distribution of the same phenomena in majority, or “macro”, varieties – such as French, Italian, Spanish, Brazilian Portuguese, Estonian, Finnish, Czech and Serbian. The second part of the paper, then, provides an overview of the content of each original paper collected in the special issue.
Broad‐spectrum stress tolerance conferred by suppressing jasmonate signaling attenuation in Arabidopsis JASMONIC ACID OXIDASE mutants
Authors: Marquis Valentin , Smirnova Ekaterina , Graindorge Stéfanie , Delcros Pauline , Villette Claire , Zumsteg Julie , Heintz Dimitri , Heitz Thierry 
Published: November 2021

SUMMARYJasmonate signaling for adaptative or developmental responses generally relies on an increased synthesis of the bioactive hormone jasmonoyl‐isoleucine (JA‐Ile), triggered by environmental or internal cues. JA‐Ile is embedded in a complex metabolic network whose upstream and downstream components strongly contribute to hormone homeostasis and activity. We previously showed that JAO2, an isoform of four Arabidopsis JASMONIC ACID OXIDASES, diverts the precursor jasmonic acid (JA) to its hydroxylated form HO‐JA to attenuate JA‐Ile formation and signaling. Consequently, JAO2‐deficient lines have elevated defenses and display improved tolerance to biotic stress. Here we further explored the organization and regulatory functions of the JAO pathway. Suppression of JAO2 enhances the basal expression of nearly 400 JA‐regulated genes in unstimulated leaves, many of which being related to biotic and abiotic stress responses. Consistently, non‐targeted metabolomic analysis revealed the constitutive accumulation of several classes of defensive compounds in jao2‐1 mutant, including indole glucosinolates and breakdown products. The most differential compounds were agmatine phenolamides, but their genetic suppression did not alleviate the strong resistance of jao2‐1 to Botrytis infection. Furthermore, jao2 alleles and a triple jao mutant exhibit elevated survival capacity upon severe drought stress. This latter phenotype occurs without recruiting stronger abscisic acid responses, but relies on enhanced JA‐Ile signaling directing a distinct survival pathway with MYB47 transcription factor as a candidate mediator. Our findings reveal the selected spectrum of JA responses controlled by the JAO2 regulatory node and highlight the potential of modulating basal JA turnover to pre‐activate mild transcriptional programs for multiple stress resilience.