bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amplifying the antidiabetic actions of glucagon‐like peptide‐1: Potential benefits of new adjunct therapies
Authors: Tanday Neil , Flatt Peter R. , Irwin Nigel 
Published: September 2021

AbstractClinically approved for the treatment of diabetes and obesity, glucagon‐like peptide‐1 (GLP‐1) receptor agonists display prominent glucose‐ and weight‐lowering effects as well as positive cardioprotective and neuroprotective actions. Despite these benefits, bariatric surgery remains superior in producing robust and sustained weight loss alongside improvements in metabolic control with possible diabetes remission. The current review considers the potential for adjunct therapies to augment the therapeutic actions of GLP‐1 receptor agonists. In this regard, several gut‐derived hormones also, modulated by bariatric surgery, display additive properties when combined with GLP‐1 receptor agonists in both preclinical and clinical studies. In addition, glucocorticoids and oestrogen have shown promise in augmenting the biological actions of GLP‐1 in animal models. Additionally, GLP‐1 efficacy can also be enhanced by use of compounds that prolong GLP‐1 receptor coupling to potentiate downstream receptor signalling. Taken together, therapies that activate GLP‐1 receptor signalling, in combination with various other cell signalling pathways, show potential for treating type 2 diabetes and obesity with superiority over GLP‐1 receptor agonist therapy alone.
Formalizing agricultural rentals in China: Does local public action help?
Authors: Qiu Tongwei , Shi Xinjie , Luo Biliang 
Published: September 2021

SummaryMotivationFrom 2002, local governments and village collectives in China have been allowed and encouraged to facilitate and formalize agricultural land rentals. Before, most temporary land transfers within villages were informal agreements between farmers who knew each other well. Changes were introduced to make it easier for outsiders to rent land, and thereby bring capital and know‐how to the village.PurposeThis study tests whether public intervention increases market‐based land rentals and how it affects rentals among acquaintances.Methods and approachDrawing on data from the 2017 and 2019 China Family Panel Surveys conducted in 29 provinces, ordinary least squares and fixed effect models are used to test the effects of public intervention in agricultural rentals.FindingsPublic intervention increases land rentals and the widespread use of written contracts for defined periods. Rentals between acquaintances within the same village have become more formal, with rents at market levels. When local authorities facilitate land rentals in villages, all rentals become more formal, with market‐based rents.Policy implicationsPublic intervention in Chinese agricultural land rental has reduced transaction costs for outsiders, has led to more market‐based rentals, and has facilitated land transfers—in a setting where some farmers are looking to switch from farming to off‐farm work. Policy changes have worked.
The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies
Authors: Unchiti Kantarakorn , Leurcharusmee Prangmalee , Samerchua Artid , Pipanmekaporn Tanyong , Chattipakorn Nipon , Chattipakorn Siriporn C. 
Published: September 2021

AbstractNeurological disorders following brain injuries and neurodegeneration are on the rise worldwide and cause disability and suffering in patients. It is crucial to explore novel neuroprotectants. Dexmedetomidine, a selective α2‐adrenoceptor agonist, is commonly used for anxiolysis, sedation and analgesia in clinical anaesthesia and critical care. Recent studies have shown that dexmedetomidine exerts protective effects on multiple organs. This review summarized and discussed the current neuroprotective effects of dexmedetomidine, as well as the underlying mechanisms. In preclinical studies, dexmedetomidine reduced neuronal injury and improved functional outcomes in several models, including hypoxia‐induced neuronal injury, ischaemic‐reperfusion injury, intracerebral haemorrhage, post‐traumatic brain injury, anaesthetic‐induced neuronal injury, substance‐induced neuronal injury, neuroinflammation, epilepsy and neurodegeneration. Several mechanisms are associated with the neuroprotective function of dexmedetomidine, including neurotransmitter regulation, inflammatory response, oxidative stress, apoptotic pathway, autophagy, mitochondrial function and other cell signalling pathways. In summary, dexmedetomidine has the potential to be a novel neuroprotective agent for a wide range of neurological disorders.
Seed movement in small‐scale vegetation restoration
Authors: Elliott Carole P , Commander Lucy E , Williams Matthew R , Golos Peter J 
Published: September 2021

SummaryQuantifying ecological interactions can inform restoration practitioners of the recovery of ecosystem function in restored areas. Plant–animal interactions that move seeds are critical for plant recruitment, animal food sources and ecosystem function, but seed movement immediately after sowing can affect calculations of seedling emergence in restored areas. We set up seed cafeterias in undisturbed, native vegetation and restored areas to quantify and compare the removal of seeds of eight native plant species of banded ironstone ranges to determine the recovery of this ecological interaction and the potential effect on monitoring protocols. Overall, the average amounts of seeds removed from cafeterias over two days were between 17 and 23%, but this varied considerably between replicates. Seeds with or without a food body (i.e. elaiosome) were both removed from cafeterias by invertebrates. Seeds removed by invertebrates (most likely ants) after surface sowing for restoration are expected to negatively affect calculations of seedling emergence because the known quantity of sown seeds has been reduced, deflating emergence calculations. Restoration protocols should consider the potential negative effect of seed movement on seedling emergence. Encouragingly, these restoration areas have maintained ecological interactions that move seeds in the landscape at comparable levels to undisturbed vegetation.
Long‐term MRI changes in a patient with Kelch‐like protein 11‐associated paraneoplastic neurological syndrome
Authors: Ishikawa Hidehiro , Mandel‐Brehm Caleigh , Shindo Akihiro , Cady Martha A. , Mann Sabrina A. , Niwa Atsushi , Miyashita Koichi , Ii Yuichiro , Zorn Kelsey C. , Taniguchi Akira , Maeda Masayuki , Wilson Michael R. , DeRisi Joseph L. , Tomimoto Hidekazu 
Published: September 2021

AbstractBackground and purposeThe aim of this study was to identify the long‐term radiological changes, autoantibody specificities, and clinical course in a patient with kelch‐like protein 11 (KLHL11)‐associated paraneoplastic neurological syndrome (PNS).MethodsSerial brain magnetic resonance images were retrospectively assessed. To test for KLHL11 autoantibodies, longitudinal cerebrospinal fluid (CSF) and serum samples were screened by Phage‐display ImmunoPrecipitation and Sequencing (PhIP‐Seq). Immunohistochemistry was also performed to assess for the presence of KLHL11 in the patient's seminoma tissue.ResultsA 42‐year‐old man presented with progressive ataxia and sensorineural hearing loss. Metastatic seminoma was detected 11 months after the onset of the neurological symptoms. Although immunotherapy was partially effective, his cerebellar ataxia gradually worsened over the next 8 years. Brain magnetic resonance imaging revealed progressive brainstem and cerebellar atrophy with a “hot‐cross‐bun sign”, and low‐signal intensity on susceptibility‐weighted imaging (SWI) in the substantia nigra, red nucleus and dentate nuclei. PhIP‐Seq enriched for KLHL11‐derived peptides in all samples. Immunohistochemical staining of mouse brain with the patient CSF showed co‐localization with a KLHL11 commercial antibody in the medulla and dentate nucleus. Immunohistochemical analysis of seminoma tissue showed anti‐KLHL11 antibody‐positive particles in cytoplasm.ConclusionsThis study suggests that KLHL11‐PNS should be included in the differential diagnosis for patients with brainstem and cerebellar atrophy and signal changes not only on T2‐FLAIR but also on SWI, which might otherwise be interpreted as secondary to a neurodegenerative disease such as multiple system atrophy.
Development and validation of the dialysis dementia risk score: A retrospective, population‐based, nested case‐control study
Authors: Ling Tsai‐Chieh , Chang Chiung‐Chih , Li Chung‐Yi , Sung Junne‐Ming , Sun Chien‐Yao , Tsai Kuen‐Jer , Cheng Ya‐Yun , Wu Jia‐Ling , Kuo Yi‐Ting , Chang Yu‐Tzu 
Published: September 2021

AbstractBackgroundDementia is prevalent and underdiagnosed in the dialysis population. We aimed to develop and validate a simple dialysis dementia scoring system to facilitate identification of individuals who are at high risk for dementia.MethodsWe applied a retrospective, nested case‐control study design using a national dialysis cohort derived from the National Health Insurance Research Database in Taiwan. Patients aged between 40 and 80 years were included and 2940 patients with incident dementia were matched to 29,248 non‐dementia controls. All subjects were randomly divided into the derivation and validation sets with a ratio of 4:1. Conditional logistic regression models were used to identify factors contributing to the risk score. The cutoff value of the risk score was determined by Youden's J statistic and the graphic method.ResultsThe dialysis dementia risk score (DDRS) finally included age and 10 comorbidities as risk predictors. The C‐statistic of the model was 0.71 (95% confidence interval [CI] 0.70–0.72). Calibration revealed a strong linear relationship between predicted and observed dementia risk (R2 = 0.99). At a cutoff value of 50 points, the high‐risk patients had an approximately three‐fold increased risk of having dementia compared to those with low risk (odds ratio [OR] 3.03, 95% CI 2.78–3.31). The DDRS performance, including discrimination (C‐statistic 0.71, 95% CI 0.69–0.73) and calibration (p value of Hosmer−Lemeshow test for goodness of fit = 0.18), was acceptable during validation. The OR value (2.82, 95% CI 2.37–3.35) was similar to those in the derivation set.ConclusionThe DDRS system has the potential to serve as an easily accessible screening tool to determine the high‐risk groups who deserve subsequent neurological evaluation in daily clinical practice.
Eliciting symptom‐diagnosis knowledge from online medical Q&A
Authors: Yu Ying , Huang Hao 
Published: September 2021

AbstractWith the objective to automatically detect diseases from symptoms in free‐text data, a methodology to extract symptom‐diagnosis knowledge from online medical textual data in Q&A domain is proposed in this paper: (1) a term frequency‐inverse document frequency and PRECISION method is adopted to retrieve symptom words from unstructured text; (2) a variable precision rough set based genetic algorithm is applied to reduce redundant symptom words, and a rough set based rule is utilized for adding discriminative symptom words assisting to discriminate diseases sharing similar symptoms; (3) by employing fuzzy linguistic variables to express the risk level of disease or severity level of symptoms, a knowledge base with fuzzy belief structure is generated. Using data extracted from a Chinese medical Q&A forum for training and testing, some classical gastrointestinal diseases serve as a case study to evaluate the efficiency of the proposed methodology. Subsequently performance comparisons are made between the proposed methodology and some other classifiers, such as the decision tree algorithms including ID3 and J45, and the Bayesian network classifier. The comparative results demonstrate that the proposed methodology outperforms the decision tree algorithms and the Bayesian network classifier.
Segmentation of malignant tumours in mammogram images: A hybrid approach using convolutional neural networks and connected component analysis
Authors: Roy Abhijit , Singh Bikesh Kumar , Banchhor Sumit K. , Verma Kesari 
Published: September 2021

AbstractThe segmentation of breast lesions is an important step in the computer‐aided analysis of the mammogram. The presence of noise in mammograms makes lesion detection challenging particularly for complex malignant lesions. Pre‐processing techniques can deal with the noise issue but distorts the important shape features. This motivates us to propose a novel hybrid approach by combining a convolution neural network (CNN) with connected component analysis (CCA) to segment malignant breast lesions without any pre‐processing to avoid any distortion in image sharpness at the initial stages. Two well‐known segmentation techniques namely, K‐means (KM) and Fuzzy c‐means (FCM) are also used to compare the results. From a pool of 1045 mammographic cancer images acquired from the Digital Database for Screening Mammography (DDSM), 1016 are used for training and validation, and 29 are used for testing. All three results (Hybrid, KM and FCM) are compared against the results by the expert Radiologist. The results indicate that, among various segmentation techniques, the proposed hybrid approach achieves the highest accuracy (90%), Matthew's correlation coefficient (0.79), Jaccard index (0.73) and the Dice similarity coefficient (0.84). Other performance evaluation techniques such as; precision, sensitivity, specificity, false‐positive rate, false discovery rate, negative predictive value and false‐negative rate also show the superior performance of the proposed hybrid approach. Statistical analysis (Mann–Whitney U test, T‐test, Chi‐square test, Kolmogorov–Smirnov test and Wilcoxon test), graphical analysis (Regression and Bland–Altman plots) and receiver operating characteristic curve further demonstrate the stability and consistency of the results.
Common but differentiated rights and responsibilities in tuna fisheries management
Authors: Sinan Hussain , Bailey Megan , Hanich Quentin , Azmi Kamal 
Published: September 2021

AbstractThe UN Law of the Sea Convention (LOSC) and one of the implementing agreements of the Convention—the UN Fish Stocks Agreement (UNFSA)—mandates all states to cooperate in the management of highly migratory and straddling fish stocks. In doing so, the UNFSA specifies that the special requirements of developing states need to be taken into account. To date, except in the Western and Central Pacific Fisheries Commission (WCPFC), there is no formal mechanism to identify these differential responsibilities in tuna regional fisheries management organizations (RFMOs). Although some conservation and management measures exempt small‐scale and artisanal fishing vessels, power imbalances within RFMOs tend to favour the interests of more developed and larger distant water fishing nations over those of small developing coastal states. To facilitate the implementation of differentiated responsibilities as mandated in UNFSA, in this study we develop a three‐step framework that could be applied in the case of new conservation and management measure proposals. The framework has also been tested based on two developing countries and compared with a developed state in the Indian Ocean Tuna Commission and the adopted resolutions in 2019. To facilitate better transparency and equitable decision‐making processes across RFMOs, this framework could be adapted based on member states' fisheries management objectives and target and non‐target species.
How democratic is government really? The impact of subnational regime variation on evaluations of democracy
Authors: Fidalgo Amanda 
Published: September 2021

AbstractDemocracy is not an exclusively national concept, and subnational governments vary in respect for democratic norms and institutions. In subnational authoritarian enclaves, incumbents manipulate elections using fraud, corruption, institutional manipulation, or repression to maintain power. While we know a fair amount about how these authoritarian enclaves form and democratize, we know much less about how they affect the people that live in them. Does subnational democracy influence evaluations of democratic performance? I argue that individuals incorporate subnational outcomes into overall evaluations of democracy, and that subnational democracy positively influences these evaluations. To test this argument, I combine a new measure of subnational democracy, the Subnational Electoral Democracy Scale, with the fifth and sixth waves of the World Values Survey. I find that people living in states with high electoral democracy scores are likely to believe that elections are not manipulated, human rights are protected, and that their country is democratic.
Post‐hoc analysis on the long‐term response to fixed‐dose prophylaxis with N8‐GP in patients with haemophilia A
Authors: Tiede Andreas , Hampton Kingsley , Jiménez‐Yuste Victor , Young Guy , Benchikh el Fegoun Soraya , Chowdary Pratima 
Published: September 2021

AbstractIntroductionChallenges with personalised prophylaxis in haemophilia remain, including designing unique dosing schedules that require continual adjustments and monitoring using complex sampling procedures.AimTo assess long‐term efficacy and pharmacokinetic outcomes with fixed‐dose N8‐GP prophylaxis.MethodsDescriptive analyses were performed on data from the pathfinder 2 and pathfinder 5 trials of patients with severe haemophilia A. Bleed frequency and reoccurrence were assessed in relation to several clinical criteria of interest. Bleed risk relative to time since last dose was assessed using calculated annualised bleeding rate (ABR). Long‐term ABR and mean factor VIII (FVIII) trough levels were assessed in patients who received consistent N8‐GP prophylaxis every 4 days (Q4D).ResultsDuring pathfinder 2, 117/136 patients with study‐drug exposure of ≥600 days experienced bleeding episodes; 8.6% of bleeds were reoccurring bleeds; bleed reoccurrence decreased over time. For patients who received consistent Q4D prophylaxis across the trial (n = 61), mean ABR decreased from 3.5 bleeds/year (Year 1) to 1.6 bleeds/year (Year 6); mean FVIII trough levels stabilised at approximately 5% (Year 6). Across patients who received prophylaxis at some point during pathfinder 2 (n = 177), 125/126 (99%) reoccurring bleeds were joint bleeds. For patients receiving Q4D prophylaxis, bleeding risk generally increased as the time since the last prophylaxis dose increased. A similar reduction in ABR and stabilisation of trough level was observed in pathfinder 5.ConclusionLong‐term exposure (> 5 years) to fixed‐dose N8‐GP prophylaxis resulted in a protective haemostatic effect, with reduction in bleed frequency and reoccurrence, and stabilisation of FVIII trough level over time.
The prognostic significance of pleomorphism in gastrointestinal stromal tumours
Authors: Isidro Raymond A , Hornick Jason L 
Published: September 2021

AimGastrointestinal stromal tumours (GISTs) typically show uniform nuclear morphology, with spindle cell, epithelioid or mixed histology. Risk of progression in GIST is estimated based on anatomical site, tumour size and mitotic index. Pleomorphic GISTs are rare and have not been systematically investigated. We evaluated the prognostic significance of pleomorphism in GIST.Methods and resultsIn total, 108 of 2517 (4.3%) GISTs reviewed between 2000 and 2021 were reported to show pleomorphism. Seventeen cases underwent mutational testing. Pleomorphism was noted prior to therapy in 37 GISTs, affecting 18 males and 19 females, with a mean age of 55.4 years. Most tumours arose in the stomach (n = 15) or small intestine (n = 19), with a mean size of 9.2 cm and a median mitotic rate of seven per 5 mm2; the median follow‐up was 5.7 years. Immunohistochemistry for KIT was positive in 36 (97.3%) tumours. Mutational testing revealed KIT and PDGFRA mutations in 68.4 and 21.0% of cases, respectively; no SDHX, KIT or PDGFRA alterations were found in two cases (one of which was succinate dehydrogenase‐deficient). According to standard risk assessment criteria for progressive disease, 18 tumours were high‐risk, five were moderate‐risk, four were low‐risk, five were very low‐risk and one had no risk. Disease progression was exclusive to high‐risk tumours (79%; P < 0.001).ConclusionsPleomorphism is present prior to therapy in approximately 2% of GISTs and is most prevalent in high‐risk gastric and small intestinal GISTs. Pleomorphism appears to have no prognostic significance beyond conventional risk stratification.
Endodontic inflammatory disease: A risk indicator for a first myocardial infarction
Authors: Sebring Dan , Buhlin Kåre , Norhammar Anna , Rydén Lars , Jonasson Peter ,   EndoReCo, Lund Henrik , Kvist Thomas 
Published: September 2021

AbstractAimTo study the association between endodontic inflammatory disease and a first myocardial infarction (MI).MethodologyThe study comprised 805 patients with recent experience of a first MI, each gender, age and geographically matched with a control. Panoramic radiographs were available for 797 patients and 796 controls. Endodontic inflammatory disease was assessed radiographically. The sum of decayed, missing and filled teeth (DMFT) was calculated, and the number of root filled teeth and teeth with periapical lesions were recorded. The associated risk of a first MI was expressed as odds ratios (OR) with 95% confidence intervals (CI), unadjusted and adjusted for confounders (family history of cardiovascular disease, smoking habits, marital status, education and diabetes).ResultsPatients who had suffered a first MI had higher DMFT (mean 22.5 vs. 21.9, p = .013) and more missing teeth (mean 7.5 vs. 6.3; p < .0001) than the healthy controls. The number of missing teeth was associated with an increased risk of a first MI (adjusted OR 1.04; CI 1.02–1.06). Conversely, decay‐free, filled teeth were associated with decreased risk (adjusted OR 0.98; CI 0.96–1.00). Analysis based on age disclosed the following variables to be associated with an increased risk of a first MI: number of decayed teeth (adjusted OR 1.18; CI 1.02–1.37, in patients <60 years), any primary periapical lesion (adjusted OR 1.57; CI 1.08–2.29, in patients <65 years) and the proportion of root filled teeth (adjusted OR 1.18; CI 1.03–1.36, in patients ≥65 years).ConclusionsMore missing teeth was independently associated with an increased risk of a first MI. In addition, endodontic inflammatory disease may contribute as an independent risk factor to cardiovascular disease since untreated caries, periapical lesions and root fillings, depending on age, were significantly associated with a first MI.