bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, synthesis and biological evaluation of benz‐fused five‐membered heterocyclic compounds as tubulin polymerization inhibitors with anticancer activities
Authors: Komuraiah Buduma , Ren Yichang , Xue Mingming , Cheng Binbin , Liu Jin , Liu Yao , Chen Jianjun 
Published: February 2021

AbstractA series of benz‐fused five‐membered heterocyclic compounds were designed and synthesized as novel tubulin inhibitors targeting the colchicine binding site. Among them, compound 4d displayed the highest antiproliferative activity against four cancer cell lines with an IC50 value of 4.9 μM in B16‐F10 cells. Compound 4d effectively inhibited tubulin polymerization in vitro (IC50 of 13.1 μM). Further, 4d induced cell cycle arrest in G2/M phase. Finally, 4d inhibited the migration of cancer cells in a dose‐dependent manner. In summary, these results suggest that compound 4d represents a new class of tubulin inhibitors deserving further investigation.
Exercise training and reproductive outcomes in women with polycystic ovary syndrome: A pilot randomized controlled trial
Authors: Benham Jamie L. , Booth Jane E. , Corenblum Bernard , Doucette Steve , Friedenreich Christine M. , Rabi Doreen M. , Sigal Ronald J. 
Published: February 2021

AbstractObjectiveExercise is recommended for polycystic ovary syndrome (PCOS), but the most effective exercise prescription is unclear. This trial compared effects of high‐intensity interval training (HIIT), continuous aerobic exercise training (CAET) and no‐exercise control on reproductive, anthropometric and cardiometabolic outcomes in PCOS.DesignPilot randomized controlled trial.ParticipantsPreviously inactive women aged 18–40 years with PCOS.MeasurementsFeasibility outcomes included recruitment, retention, adherence to exercise and daily ovulation prediction kit (OPK) testing. Preliminary efficacy outcomes included reproductive, anthropometric and cardiometabolic health markers.ResultsForty‐seven women were randomized to no‐exercise control (n = 17), HIIT (n = 16), or CAET (n = 14). Forty (85%) participants completed the trial. Median exercise adherence was 68% (IQR 53%, 86%). Median daily OPK‐testing adherence in the first half of the intervention was 87% (IQR 61%, 97%) compared with 65% (IQR 0%, 96%) in the second half. Body mass index decreased significantly in CAET compared with control (−1.0 kg/m2, p = .01) and HIIT (−0.9 kg/m2, p = .04). Mean waist circumference decreased in all groups (−7.3 cm, −6.9 cm, −4.5 cm in HIIT, CAET and control) with no significant between‐group differences. Mean LDL‐C was significantly reduced for HIIT compared to CAET (−0.33 mmol/L, p = .03). HDL‐C increased in HIIT compared with control (0.18 mmol/L, p = .04).ConclusionsThere were feasibility challenges with adherence to daily ovulation assessment limiting the ability to analyse the effect of the exercise interventions on ovulation. CAET and HIIT were both effective at improving anthropometrics and some cardiometabolic health markers. Further studies need to determine optimal and acceptable exercise prescriptions for this population.
Aesthetic outcomes of non‐functional immediately restored single post‐extraction implants with and without connective tissue graft: A multicentre randomized controlled trial
Authors: Ferrantino Luca , Camurati Andrea , Gambino Paolo , Marzolo Michele , Trisciuoglio Davide , Santoro Giacomo , Farina Vittorio , Fontana Filippo , Asa'ad Farah , Simion Massimo 
Published: February 2021

AbstractObjectivesTo compare the 1‐year aesthetic results of flapless single implants, placed in fresh extraction sockets with bone replacement and immediate provisional restoration with or without a connective tissue graft (CTG).Material and MethodsThe present study proposes a partially blinded multicentre parallel randomized controlled trial, where computer‐generated tables were used for central randomization to allocate treatments. A total of 59 of the 60 patients screened by eight private practices in Northern Italy fulfilled the inclusion criteria. Immediate implants were placed in a fresh extraction socket with a non‐functional immediate provisional restoration with (Test group) or without (Control group) a CTG. The primary outcome variable was the implant Crown Aesthetic Index (ICAI) at the 1‐year follow‐up.ResultsICAI for the 59 randomized patients (Test group = 31, Control group = 28) at the 1‐year follow‐up was 4.69 (95% CI = 3.16–6.22) for the Test group and 3.45 (95% CI = 1.83–5.08) for the Control group, without statistically significant difference between the two groups (p = .086). One implant failure was recorded in each group, resulting in an implant survival rate of 96.8% [95% CI = 83.3–99.9] for the Test group and 96.4% [95% CI = 81.7–99.9] for the Control group. Other secondary outcome variables and complication rates were comparable across the two groups.ConclusionsWithin the limitations of the present clinical trial, the results suggested that the adjunct use of CTG is not mandatory to achieve successful aesthetic outcomes for a well‐planned immediate implant placement with immediate non‐functional provisional restoration in a fresh extraction socket.
Protocol for a multi‐centre observational and mixed methods pilot study to identify factors predictive of poor functional recovery after major gastrointestinal surgery and strategies to enhance uptake of perioperative optimization
Authors: Daniels Sarah L. , Lee Matthew J. , Moug Susan , Wilson Tim R. , Burton Maria , George Jayan , Brown Steven R. , Wyld Lynda 
Published: February 2021

AbstractIntroductionNational datasets report large variations in outcomes from older people (≥65 years) between different UK surgical units. This implies that not all patients receive the same level of care or access to resources, such as rehabilitation or allied health professional input. This might impact functional decline.AimsOur aim is to evaluate the baseline status of older patients facing major gastrointestinal surgery and the impact of variation in perioperative assessment and provision of perioperative support on functional outcomes. Patients’ experiences and views of assessment and optimization will be explored via integrated qualitative semi‐structured interviews.Methods and analysisThis multi‐centre, pilot cohort study will include patients ≥65 years presenting via both elective and emergency pathways at three to five South Yorkshire NHS hospitals (Clinical Trials registration NCT04545125). The primary outcome is functional recovery measured using the World Health Organization Disability Assessment Schedule 2.0 at 6 weeks post‐operation. Secondary outcomes include feasibility, quality of life, length of stay and complication rate. An opportunistic sample size of 120 has been estimated and will inform the design of a future, adequately powered study. For the qualitative study, 20–30 semi‐structured patient interviews will be undertaken with patients from the cohort study to explore experiences of assessment and optimization. Interviews will be digitally recorded, transcribed verbatim and analysed according to the framework approach.Ethics and disseminationThis study has been approved by the National Health Service Research Ethics Committee and is registered centrally with Health Research Authority. It has been adopted by the National Institute for Health Research Portfolio scheme. Dissemination will be via international and national surgical and geriatric conferences.
Harassment‐induced changes in lion space use as a conflict mitigation tool
Authors: Petracca Lisanne S. , Frair Jacqueline L. , Bastille‐Rousseau Guillaume , Macdonald David W. , Loveridge Andrew J. 
Published: February 2021

AbstractHuman‐wildlife conflict represents a substantial threat to rural livelihoods and species persistence. Directed harassment (i.e., hazing) is one method for mitigating conflict, though gauging its effectiveness is often complicated by a lack of replication, controls, or effective contrasts. Herein we assessed whether African lions (Panthera leo) shifted their space use in response to a hazing program intended to deter lions from community lands adjacent to Hwange National Park, Zimbabwe. Using GPS‐collared lions (n = 16) from unique prides, we investigated the degree to which individuals exhibited (a) a large‐scale response by shifting their home ranges away from community lands, or (b) a fine‐scale response by increasingly avoiding areas near households post‐program initiation. Responses between “at‐risk” (those exposed to the program; n = 5) and “protected” (n = 11) lions varied, with at‐risk males shifting their home ranges to include 12.08% more national park and 9.04% less community lands post‐program (median), a shift not replicated by at‐risk females nor protected lions. However, the majority of at‐risk lions demonstrated increased attraction to households post‐program. We demonstrated that while aversive stimulus approaches may alter large‐scale space use by individual lions, constraints imposed by social structure and available habitat alternatives will affect the level of effort required to achieve program success.
Reproducibility and validity of the Functional Communication Classification System for young children with cerebral palsy
Authors: Caynes Katy , Rose Tanya A , Burmester Debbie , Ware Robert S , Johnston Leanne M 
Published: February 2021

AimTo examine interrater agreement and validity of the Functional Communication Classification System (FCCS) for young children with cerebral palsy (CP) aged 2 or 3 years.MethodSpeech‐language pathologist (SLP) and parent FCCS ratings for 31 children with CP (aged 2y, n=16; aged 3y, n=15; 18 males, 13 females) were examined for interrater agreement using a weighted Cohen’s kappa statistic. Relationships between FCCS (SLP) ratings and: (1) concurrent validity with the Language Use Inventory, a standardized pragmatic assessment for children aged 18 to 47 months, (2) gross motor and fine motor function, (3) associated impairments (visual and intellectual), and (4) primary expressive communication mode were examined using Spearman’s correlation coefficients.ResultsAlmost perfect interrater agreement between SLP and parent FCCS ratings were found (kw=0.94). Correlations with FCCS (SLP) were excellent for pragmatic function (rs=−0.83, p<0.001), intellectual function (rs=0.89, p<0.001), and primary expressive communication mode (rs=0.92, p<0.001). Correlations were good for gross motor function (rs=0.72, p<0.001) and visual impairment (rs=0.70, p<0.001) and fair for fine motor function (rs=0.53, p<0.002). Analysis was unwarranted for epilepsy (n=1 out of 31) and hearing‐associated impairments (n=0 out of 31).InterpretationThe FCCS has excellent interrater agreement and validity for communication classification of children with CP aged 2 or 3 years and is highly suitable for surveillance and research purposes.What this paper adds

The Functional Communication Classification System (FCCS) is a valid instrument for children with cerebral palsy (CP) aged 2 or 3 years.

Excellent agreement exists between speech‐language pathologist and parent FCCS ratings.

The FCCS has excellent correlation with intelligence, pragmatic function, and primary expressive mode.

Stronger correlations with the Gross Motor Function Classification System and vision exist for children aged 2 or 3 years.

Weaker correlations with manual ability exist when compared to older children with CP.
Spontaneous healing of a ruptured mycotic aneurysm of the posterior mitral leaflet: Unexpected resolution of a severe mitral regurgitation
Authors: Ruisanchez Villar Cristina , Gonzalez Lizarbe Sofia , Lerena Saenz Piedad , Gil Ongay Aritz , Borderias Villarroel Teresa , Teira Calderon Andrea , Cabrera Rubio Indira , Cuesta Cosgaya Jose Maria 
Published: February 2021

AbstractMycotic mitral valve aneurysm is an uncommon complication that rarely appears in isolated mitral valve endocarditis. The weakened aneurysmal wall may rupture, causing severe mitral regurgitation. In this situation surgery is essential. We present a case of a rare complicated mycotic posterior mitral aneurysm. After completing the antibiotic course for Streptococcus agalactiae infective endocarditis, an unexpected healing process within the aneurysm led to the virtual disappearance of the mitral regurgitation and remarkably changed the patient's clinical outcome. We emphasize the key role of three‐dimensional transesophageal echocardiography, as it is becoming the reference imaging technique for infective endocarditis.
Fostering global value chains through international agreements: Evidence from Vietnam
Authors: Malesky Edmund J. , Milner Helen V. 
Published: February 2021

AbstractWhich is more reassuring to foreign investors—domestic laws or international agreements? A substantial literature argues that foreign investment may be underprovided, because governments cannot offer credible guarantees that judicial institutions are impartial and that investors will be able to fairly resolve disputes with business partners and enforce contracts. This time inconsistency problem deters profitable business partnerships between foreign investors and domestic firms in the host country. Consequently, for emerging market leaders seeking to deepen their countries’ integration into global value chains (GVCs), enhancing the confidence of investors in contracting institutions is critical. In this paper, we study the emerging market of Vietnam to examine which type of reassurance mechanism is most successful. Using a survey of 1,583 foreign firms, we inform investors about either a domestic law or international treaty designed to strengthen commercial arbitration procedures. We find that priming foreign firms about the international investment agreement has a larger positive impact on their views about the future profitability of their projects and the likelihood of contracting with other firms in GVCs than simply learning about the commitments in domestic law.
Climatic and evolutionary contexts are required to infer plant life history strategies from functional traits at a global scale
Authors: Kelly Ruth , Healy Kevin , Anand Madhur , Baudraz Maude E. A. , Bahn Michael , Cerabolini Bruno E. L. , Cornelissen Johannes H. C. , Dwyer John M. , Jackson Andrew L. , Kattge Jens , Niinemets Ülo , Penuelas Josep , Pierce Simon , Salguero‐Gómez Roberto , Buckley Yvonne M. 
Published: February 2021

AbstractLife history strategies are fundamental to the ecology and evolution of organisms and are important for understanding extinction risk and responses to global change. Using global datasets and a multiple response modelling framework we show that trait‐climate interactions are associated with life history strategies for a diverse range of plant species at the global scale. Our modelling framework informs our understanding of trade‐offs and positive correlations between elements of life history after accounting for environmental context and evolutionary and trait‐based constraints. Interactions between plant traits and climatic context were needed to explain variation in age at maturity, distribution of mortality across the lifespan and generation times of species. Mean age at maturity and the distribution of mortality across plants’ lifespan were under evolutionary constraints. These findings provide empirical support for the theoretical expectation that climatic context is key to understanding trait to life history relationships globally.
The role of new medical treatments for the management of developmental and epileptic encephalopathies: Novel concepts and results
Authors: Johannessen Landmark Cecilie , Potschka Heidrun , Auvin Stéphane , Wilmshurst Jo M. , Johannessen Svein I. , Kasteleijn‐Nolst Trenité Dorothée , Wirrell Elaine C. 
Published: February 2021

AbstractDevelopmental and epileptic encephalopathies (DEEs) are among the most challenging of all epilepsies to manage, given the exceedingly frequent and often severe seizure types, pharmacoresistance to conventional antiseizure medications, and numerous comorbidities. During the past decade, efforts have focused on development of new treatment options for DEEs, with several recently approved in the United States or Europe, including cannabidiol as an orphan drug in Dravet and Lennox–Gastaut syndromes and everolimus as a possible antiepileptogenic and precision drug for tuberous sclerosis complex, with its impact on the mammalian target of rapamycin pathway. Furthermore, fenfluramine, an old drug, was repurposed as a novel therapy in the treatment of Dravet syndrome. The evolution of new insights into pathophysiological processes of various DEEs provides possibilities to investigate novel and repurposed drugs and to place them into the context of their role in future management of these patients. The purpose of this review is to provide an overview of these new medical treatment options for the DEEs and to discuss the clinical implications of these results for improved treatment.
External validation of automated focal cortical dysplasia detection using morphometric analysis
Authors: David Bastian , Kröll‐Seger Judith , Schuch Fabiane , Wagner Jan , Wellmer Jörg , Woermann Friedrich , Oehl Bernhard , Van Paesschen Wim , Breyer Tobias , Becker Albert , Vatter Hartmut , Hattingen Elke , Urbach Horst , Weber Bernd , Surges Rainer , Elger Christian Erich , Huppertz Hans‐Jürgen , Rüber Theodor 
Published: February 2021

AbstractObjectiveFocal cortical dysplasias (FCDs) are a common cause of drug‐resistant focal epilepsy but frequently remain undetected by conventional magnetic resonance imaging (MRI) assessment. The visual detection can be facilitated by morphometric analysis of T1‐weighted images, for example, using theMorphometric Analysis Program(v2018; MAP18), which was introduced in 2005, independently validated for its clinical benefits, and successfully integrated in standard presurgical workflows of numerous epilepsy centers worldwide. Here we aimed to develop an artificial neural network (ANN) classifier for robust automated detection of FCDs based on these morphometric maps and probe its generalization performance in a large, independent data set.MethodsIn this retrospective study, we created a feed‐forward ANN for FCD detection based on the morphometric output maps of MAP18. The ANN was trained and cross‐validated on 113 patients (62 female, mean age ± SD =29.5 ± 13.6 years) with manually segmented FCDs and 362 healthy controls (161 female, mean age ± SD =30.2 ± 9.6 years) acquired on 13 different scanners. In addition, we validated the performance of the trained ANN on an independent, unseen data set of 60 FCD patients (28 female, mean age ± SD =30 ± 15.26 years) and 70 healthy controls (42 females, mean age ± SD = 40.0 ± 12.54 years).ResultsIn the cross‐validation, the ANN achieved a sensitivity of 87.4% at a specificity of 85.4% on the training data set. On the independent validation data set, our method still reached a sensitivity of 81.0% at a comparably high specificity of 84.3%.SignificanceOur method shows a robust automated detection of FCDs and performance generalizability, largely independent of scanning site or MR‐sequence parameters. Taken together with the minimal input requirements of a standard T1 image, our approach constitutes a clinically viable and useful tool in the presurgical diagnostic routine for drug‐resistant focal epilepsy.
Introduced populations of ragweed show as much evolutionary potential as native populations
Authors: McGoey Brechann V. , Stinchcombe John R. 
Published: February 2021

AbstractInvasive species are a global economic and ecological problem. They also offer an opportunity to understand evolutionary processes in a colonizing context. The impacts of evolutionary factors, such as genetic variation, on the invasion process are increasingly appreciated, but there remain gaps in the empirical literature. The adaptive potential of populations can be quantified using genetic variance–covariance matrices (G), which encapsulate the heritable genetic variance in a population. Here, we use a multivariate Bayesian approach to assess the adaptive potential of invasive populations of ragweed (Ambrosia artemisiifolia), a serious allergen and agricultural weed. We compared several aspects of genetic architecture and the structure of G matrices between three native and three introduced populations, based on phenotypic data collected in a field common garden experiment. We found moderate differences in the quantitative genetic architecture among populations, but we did not find that introduced populations suffer from a limited adaptive potential or increased genetic constraint compared with native populations. Ragweed has an annual life history, is an obligate outcrosser, and produces very large numbers of seeds and pollen grains. These characteristics, combined with the significant additive genetic variance documented here, suggest ragweed will be able to respond quickly to selection pressures in both its native and introduced ranges.
The influence of seafloor terrain on fish and fisheries: A global synthesis
Authors: Borland Hayden P. , Gilby Ben L. , Henderson Christopher J. , Leon Javier X. , Schlacher Thomas A. , Connolly Rod M. , Pittman Simon J. , Sheaves Marcus , Olds Andrew D. 
Published: February 2021

AbstractThe structure of seafloor terrain affects the distribution and diversity of animals in all seascapes. Effects of terrain on fish assemblages have been reported from most ecosystems, but it is unclear whether bathymetric effects vary among seascapes or change in response to seafloor modification by humans. We reviewed the global literature linking seafloor terrain to fish species and assemblages (96 studies) and determined that relief (e.g. depth), complexity (e.g. roughness), feature classes (e.g. substrate types) and morphology (e.g. curvature), have widespread effects on fish assemblages. Research on the ecological consequences of terrain have focused on coral reefs, rocky reefs, continental shelves and the deep sea (n ≥ 20 studies), but are rarely tested in estuaries (n = 7). Fish associate with a variety of terrain attributes, and assemblages change with variation in the depth and aspect of bathymetric features in reef and shelf seascapes, and in the deep sea. Fish from different seascapes also respond to distinct metrics, with fluctuations in slope of slope (coral reefs), rugosity (rocky reefs) and slope (continental shelves, deep sea) each linked to changes in assemblage composition. Terrain simplification from coastal urbanization (e.g. dredging) and resource extraction (e.g. trawling) can reduce fish diversity and abundance, but assemblages can also recover inside effective marine reserves. The consequences of these terrain changes for fish and fisheries are, however, rarely measured in most seascapes. The key challenge now is to examine how terrain modification and conservation combine to alter fish distributions and fisheries productivity across diverse coastal seascapes.
Study on the fracture behavior of prefabricated fissures granite based on DIC and laser scanning techniques
Authors: Hao Jiawang , Qiao Lan , Li Zhanjin , Li Qingwen 
Published: February 2021

AbstractThe initiation, propagation, and coalescence of cracks in the rock bridge are the root causes of rock failure. However, the identification of cracks propagation paths is a problem in rock mechanics. This paper studies the evolutionary law of the strain field in the rock bridge region of granite with pre‐fissures using 3D‐DIC after equivalence and simplification. Based on the real crack initiation mechanism of “relative slip between regions” proposed in this paper, combined with the priority order of crack propagation at the edge of the rock bridge, the pattern of cracks propagation and coalescence was obtained. We analyze the fracture characteristics in roughness and morphology to verify the validity of the proposed mechanism. The tensile and shear failure areas around the rock bridge were identified quantitatively, and the roughness, fractal dimension, and energy consumption of the sections formed by tensile failure and shear failure are different.