bluuebunny/crossref_metadata_2025_split huggingface dataset:
Switching to aflibercept versus continuing bevacizumab for treatment‐resistant neovascular age‐related macular degeneration: a one‐year comparative observational study
Authors: Husum Yngvil Solheim , Moe Morten Carstens , Bragadóttir Ragnheiður , Jørstad Øystein Kalsnes 
Published: February 2021

AbstractPurposeTo compare outcomes of a treatment algorithm that allows for switching treatment‐resistant neovascular age‐related macular degeneration (nAMD) eyes to aflibercept with continuing bevacizumab.MethodsRetrospective study of nAMD patients who initiated treatment in 2012 (aflibercept unavailable) and 2018 (aflibercept available). Eyes were included in the case of residual macular fluid after a minimum of 4 monthly bevacizumab injections. Only eyes in the 2018 group could then switch to aflibercept.ResultsThe study included 40 eyes from 2012 and 88 eyes from 2018. Patient characteristics were similar across the groups at baseline and 4 months. In 2018, 59 eyes (67%) were switched to aflibercept after 4 months. Mean change in BCVA from 4 months to one year was +2.8 letters in 2018 versus −1.7 letters in 2012 (p = 0.043). Mean change in BCVA from baseline to one year was +9.4 letters in 2018 (p < 0.001) and +4.4 letters in 2012 (p = 0.073). Mean change in CRT from 4 months to one year was −36 µm in 2018 versus −23 µm in 2012 (p = 0.373). Mean change in CRT from baseline to one year was −100 µm in 2018 (p < 0.001) and −75 µm in 2012 (p < 0.001). Mean number of injections given in one year was 11.8 in 2018 versus 10.4 in 2012 (p < 0.001). After one year, a majority of eyes in both groups still received treatment at 4‐week intervals.ConclusionThe study suggests that the possibility of switching eyes with treatment‐resistant nAMD to aflibercept leads to a modest visual benefit compared with continuing first‐line bevacizumab therapy.
External evaluation of the predictive performance of seven population pharmacokinetic models for phenobarbital in neonates
Authors: Ryu Sunae , Jung Woo Jin , Jiao Zheng , Chae Jung‐Woo , Yun Hwi‐yeol 
Published: February 2021

AimSeveral studies have reported population pharmacokinetic models for phenobarbital (PB), but the predictive performance of these models has not been well documented. This study aims to do external evaluation of the predictive performance in published pharmacokinetic models.MethodsTherapeutic drug monitoring data collected in neonates and young infants treated with PB for seizure control was used for external evaluation. A literature review was conducted through PubMed to identify population pharmacokinetic models. Prediction‐ and simulation‐based diagnostics, and Bayesian forecasting were performed for external evaluation. The incorporation of allometric scaling for body size and maturation factors into the published models was also tested for prediction improvement.ResultsA total of 79 serum concentrations from 28 subjects were included in the external dataset. Seven population pharmacokinetic studies of PB were identified as relevant in the literature search and included for our evaluation. The model by Voller et al showed the best performance concerning prediction‐based evaluation. In simulation‐based analyses, the normalized prediction distribution error of two models (those of Shellhaas et al and Marsot et al) obeyed a normal distribution. Bayesian forecasting with more than one observation improved predictive capability. Incorporation of both allometric size scaling and maturation function generally enhanced the predictive performance, with improvement as observed in the model of Vucicevic et al.ConclusionsThe predictive performance of published pharmacokinetic models of PB was diverse. Bayesian forecasting and incorporation of both size and maturation factors could improve the predictability of the models for neonates.
Studying the helical conformations of aspereline peptides
Authors: Blanár Eszter , Leitgeb Balázs 
Published: February 2021

AbstractAsperelines are short‐sequence peptaibol molecules, and these peptides composed of 10 residues were isolated from the Trichoderma asperellum. In our study, a detailed structural characterization was performed on the asperelines by means of molecular dynamics methods. For the aspereline peptides, the occurrence of various secondary structural elements (i.e. β‐turns and helical structures) was investigated along their entire sequences. The results derived from the simulated annealing calculations led to the observations that in the case of asperelines, the types I, III and III’ β‐turn structures, as well as their stabilizing i ← i+3 H‐bonds appeared. However, beside the different β‐turns, shorter or longer helical structures were also detected. Based on the results obtained by the molecular dynamics simulations, it was concluded that the three‐dimensional structure of aspereline peptides could be characterized by helical conformations (i.e. 310‐ and α‐helix). Nevertheless, on the basis of individual molecular dynamics trajectories, it was observed that the asperelines could adopt not only the right‐handed, but also the left‐handed helical structures.
Ursolic and betulinic semisynthetic derivatives show activity against CQ‐resistant Plasmodium falciparum isolated from Amazonia
Authors: Sol Sol de Medeiros Daniel , Tasca Cargnin Simone , Azevedo dos Santos Ana Paula , de Souza Rodrigues Moreno , Berton Zanchi Fernando , Soares de Maria de Medeiros Patrícia , de Almeida e Silva Alexandre , Bioni Garcia Teles Carolina , Baggio Gnoatto Simone Cristina 
Published: February 2021

AbstractACT’s low levels of Plasmodium parasitemia clearance are worrisome since it is the last treatment option against P. falciparum. This scenario has led to investigations of compounds with different mechanisms of action for malaria treatment. Natural compounds like ursolic acid (UA) and betulinic acid (BA), distinguished by their activity against numerous microorganisms, including P. falciparum, have become relevant. This study evaluated the antiplasmodial activity of imidazole derivatives of UA and BA against P. falciparum in vitro. Eight molecules were obtained by semisynthesis and tested against P. falciparum strains (NF54 and CQ‐resistant 106/cand isolated in Porto Velho, Brazil); 2a and 2b showed activity against NF54 and 106/cand strains with IC50 < 10 µM. They presented high selectivity indexes (SI > 25) and showed synergism when combined with artemisinin. 2b inhibited the parasite's ring and schizont forms regardless of when the treatment began. In silico analysis presented a tight bind of 2b in the topoisomerase II‐DNA complex. This study demonstrates the importance of natural derivate compounds as new candidates for malarial treatment with new mechanisms of action. Semisynthesis led to new triterpenes that are active against P. falciparum and may represent new alternatives for malaria drug development.
Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives
Authors: Alsayed Shahinda S. R. , Lun Shichun , Payne Alan , Bishai William R. , Gunosewoyo Hendra 
Published: February 2021

AbstractSeveral rationally designed isoniazid (INH), pyrazinamide (PZA) and ciprofloxacin (CPF) derivatives were conveniently synthesized and evaluated in vitro against H37Rv Mycobacterium tuberculosis (M. tb) strain. CPF derivative 16 displayed a modest activity (MIC = 16 µg/ml) and was docked into the M. tb DNA gyrase. Isoniazid‐pyrazinoic acid (INH‐POA) hybrid 21a showed the highest potency in our study (MIC = 2 µg/ml). It also retained its high activity against the other tested M. tb drug‐sensitive strain (DS) V4207 (MIC = 4 µg/ml) and demonstrated negligible cytotoxicity against Vero cells (IC50 ≥ 64 µg/ml). Four tested drug‐resistant (DR) M. tb strains were refractory to 21a, similar to INH, whilst being sensitive to CPF. Compound 21a was also inactive against two non‐tuberculous mycobacterial (NTM) strains, suggesting its selective activity against M. tb. The noteworthy activity of 21a against DS strains and its low cytotoxicity highlight its potential to treat DS M. tb.
Nicotine dependence and its association with health utility ratings among a sample of Indian dental patients
Authors: Acharya Shashidhar , Acharya Shruthi , Pentapati Kalyana Chakravarthy , Thomson William Murray 
Published: February 2021

AbstractObjectivesTo measure utility ratings and quality‐adjusted life‐years(QALYs) for nicotine dependence‐related health states using the standard gamble approach among a sample of dental patients; investigate the possible associations of nicotine dependence, and study the influences on tobacco‐related health state utilities estimates among patients.MethodsA sample of 200 adult outpatients who were current or former consumers of tobacco were included in the cross‐sectional study. Demographic, oral health self‐rating and tobacco‐related data (Fagerstrom scale for nicotine dependence, type of tobacco consumed, frequency and duration of the habit) were collected. A standard gamble method of utility valuation was also carried out.ResultsOlder age, lower educational attainment, higher frequency of consumption, increased duration of the habit, consumption of chewing tobacco, as opposed to smoking tobacco, and poor oral health were associated with higher nicotine dependence. Lower nicotine dependence, better oral health and quitting the habit were associated with better health utility estimates. QALYs lost due to the habit among the ‘low to moderate’ and ‘significant’ nicotine dependence groups were 2.7 (sd, 3.7) and 6.7 (sd, 8.0) years, respectively.ConclusionsHigher health utility ratings were seen among patients with ‘low to moderate’ nicotine dependence, better oral health status and quitters of the tobacco habit. Quality of life weights generated through this method could be used for cost‐utility analyses of tobacco cessation/prevention interventions in different settings and cultures.
Predictors of hypertensive disorders in pregnancy in women with and without polycystic ovary syndrome: The Australian Longitudinal Study of Women's Health
Authors: Bahri Khomami Mahnaz , Earnest Arul , Loxton Deborah , Teede Helena J. , Joham Anju E. 
Published: February 2021

AbstractObjectivesA higher risk of hypertensive disorders in pregnancy (HDP) is frequently reported in women with polycystic ovary syndrome (PCOS). These women, however, have a higher risk profile for HDP compared with women without PCOS. The aim of this study was to elucidate the impact of PCOS per se on the incidence of HDP through post hoc subgroup analyses of the Australian Longitudinal Study on Women's Health by level of risk.DesignLongitudinal study.PatientsOf a total of 14,247 participants, 5838 women met the inclusion criteria. Eligible women were required to report PCOS and HDP status in at least one pregnancy within the study.MeasurementsIncluded risk factors were age, body mass index, country of birth, parity, multiple pregnancy, subfertility, infertility treatment (hormonal vs. in vitro fertilization), gestational diabetes (GDM), family history of GDM and socioeconomic status. Longitudinal association between PCOS and HDP was assessed the using Cox proportional hazard regression with Efron's method.ResultsWhile PCOS was associated with a higher incidence of HDP in a univariate model [hazard ratio (HR): 1.34, 95% confidence interval (CI): 1.05, 1.72], the significance was not retained after adjustment for risk factors [HR: 1.19, 95% CI: 0.79, 1.79]. However in multivariate analysis of subgroups, PCOS remained significantly associated with higher risk of HDP in non‐obese women only [HR: 1.77, 95% CI: 1.11, 2.82].ConclusionsHigher risk of HDP in PCOS is likely related to risk factors other than PCOS.
Revealing stakeholders' motivation and influence in crane conservation in the Republic of Korea: Net‐Map as a tool
Authors: Jin Hyeyeon Sarah , Hemminger Karoline , Fong Jonathan J. , Sattler Claudia , Lee SueKyoung , Bieling Claudia , König Hannes J. 
Published: February 2021

AbstractBiodiversity conservation in protected areas requires strict legal limitations to land use. In the Civilian Control Zone (CCZ) of the Republic of Korea (ROK), military control has created an accidental sanctuary for the world's rarest crane species: the white‐naped crane (Antigone vipio) and the red‐crowned crane (Grus japonensis). Yet varying land use demands on the CCZ by stakeholders have caused disagreements in achieving cooperative crane conservation. This paper aims to clarify relevant stakeholders' interconnection and their motives that have led them to either promote or inhibit crane conservation in the Cheorwon Basin of the CCZ. To answer these questions, we conducted participatory Net‐Map interviews and identified stakeholders with a powerful role in crane conservation. Our results identify 44 stakeholders whose trust relations occurred twice as often as conflicts. More than 80% of stakeholders included in this study supported crane conservation initiatives. We attribute local farmers' increased level of environmental stewardship to two key schemes: a community‐led farming project generating financial incentives and a communication channel for stakeholders. Our case study demonstrates that Net‐Map is a valid tool to analyze human‐crane interactions, which is critical to ensure acceptance of legal restrictions to land use as well as crane conservation.
Living Donor Liver Transplant in patients with Hepatorenal Syndrome without the use of Intraoperative Renal Replacement Therapy, a single‐center experience
Authors: Singh Shweta A. , Prabhudesai Aaditya Anil , Subramaniyan Rajkumar , Madan Kaushal , Yadav Vivek , Pandey Vijaykant , Nasa Vaibhav , Goyal Sumit , Das Dibya Jyoti , Acharya Rajgopal M. , Agarwal Shaleen , Gupta Subhash 
Published: February 2021

AbstractBackgroundContinuous Renal Replacement Therapy (CRRT) is often used to support the intraoperative course during liver transplantation (LT) for patients with HRS. However, the use of intraoperative CRRT (IOCRRT) is not without its problems. Living donor liver transplantation (LDLT) is a planned operation and is possible without IOCRRT as the recipient can be optimized.AimTo study the peritransplant outcomes of patients with CLD and HRS undergoing LT without IOCRRT.MethodsAnalysis of LT program database for perioperative outcomes in patients with HRS from Feb 2017 to Dec 2018.Results87/363 (23.9%) adult LDLT patients had HRS, of whom 31 (35.6%) did not respond (NR) to standard medical therapy (SMT) prior to LT. Modified perioperative protocol enabled the NR patients (who were sicker and in persistent renal failure) to undergo LT without IOCRRT. Postoperative renal dysfunction was similar (2 in NR and 2 in R) at 1 year. Post‐LT survival was also not different at one month (83.87% in NR and 87.5% in R [p = .640]) and at 1 year (77% in NR vs 80.4% in non‐responders [p = .709]).ConclusionIOCRRT can be avoided in HRS patients undergoing LDLT without compromising their outcomes (post‐LT survival and RD), even in patients who have not responded to SMT, preoperatively.
Treatment decision‐making for a post‐traumatic malocclusion in an elderly patient: A case report.
Authors: Amadi Jude Ugochukwu , Delitala Filippo , Liberatore Gianmauro , Scozzafava Emanuele , Brevi Bruno Carlo 
Published: February 2021

AbstractTraumatic dental injuries in elderly patients are a rising trend due to demographic and social changes of the population. Older dentulous patients in good health have become increasingly common. The development of a post‐traumatic malocclusion is a common sequela resulting from mandibular condyle fracture, as in the case reported in this paper. The decision‐making process led the authors to rule out conservative treatment options and to perform orthognathic surgery on an 81‐year‐old patient, an unprecedented report in the literature. At one‐year follow‐up, prophylactic therapy, a specific surgical technique, and osteotomy fixation have restored the occlusion to the pre‐traumatic condition.
Horizontal Europeanisation among mobile doctoral candidates in the context of the European Union and the European Research Area
Authors: Schäfer Gregor 
Published: February 2021

AbstractThe processes of Europeanisation—meaning the deepening of European integration on various levels—have previously been discussed from the point of view of political science, economics, linguistics, and cultural studies, with a macro‐perspective on states, institutions, and organisations. However, Europe and the European Union (EU) are populated by individuals, who are actors of European transnationalism, which this paper conceptualises as horizontal Europeanisation. Spatial mobility is also becoming more relevant for thriving academics, and the EU aims to close ranks in Europe in the field of higher education and research. Therefore, this paper asks how the process of horizontal Europeanisation among early‐career academics manifests itself. This process is discussed against the background of the framework of the EU and the European Research Area (ERA), where academics make use of a common scientific market. The basis for the qualitative empirical analysis is 60 biographical interviews with intra‐EU mobile doctoral candidates. The findings show that the EU and ERA contribute to the processes of horizontal Europeanisation and support it. However, many decisive factors for horizontal Europeanisation lie beyond the EU and the concept of ERA. The novelty of this article as a contribution to European studies is the explanation of horizontal Europeanisation among academics through spatial mobility patterns.
Expectancy changes the self‐monitoring of voice identity
Authors: Johnson Joseph F. , Belyk Michel , Schwartze Michael , Pinheiro Ana P. , Kotz Sonja A. 
Published: February 2021

AbstractSelf‐voice attribution can become difficult when voice characteristics are ambiguous, but functional magnetic resonance imaging (fMRI) investigations of such ambiguity are sparse. We utilized voice‐morphing (self‐other) to manipulate (un‐)certainty in self‐voice attribution in a button‐press paradigm. This allowed investigating how levels of self‐voice certainty alter brain activation in brain regions monitoring voice identity and unexpected changes in voice playback quality. FMRI results confirmed a self‐voice suppression effect in the right anterior superior temporal gyrus (aSTG) when self‐voice attribution was unambiguous. Although the right inferior frontal gyrus (IFG) was more active during a self‐generated compared to a passively heard voice, the putative role of this region in detecting unexpected self‐voice changes during the action was demonstrated only when hearing the voice of another speaker and not when attribution was uncertain. Further research on the link between right aSTG and IFG is required and may establish a threshold monitoring voice identity in action. The current results have implications for a better understanding of the altered experience of self‐voice feedback in auditory verbal hallucinations.
Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis
Authors: Agnello Luisa , Colletti Tiziana , Lo Sasso Bruna , Vidali Matteo , Spataro Rossella , Gambino Caterina Maria , Giglio Rosaria Vincenza , Piccoli Tommaso , Bivona Giulia , La Bella Vincenzo , Ciaccio Marcello 
Published: February 2021

AbstractBackground and purposeTo test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls.MethodsWe enrolled 196 ALS patients and 91 controls, who included patients with ALS‐mimicking diseases and those with non‐neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay.ResultsPatients with ALS showed significantly higher levels of CSF tTau and a lower pTau/tTau ratio than controls (tTau: 245 vs. 146 pg/ml; p < 0.001; pTau/tTau ratio: 0.12 vs. 0.18; p < 0.001, respectively). No differences in pTau levels were detected. Receiver‐operating characteristic curve analysis showed a good diagnostic accuracy of tTau and pTau/tTau ratio (tTau: area under the curve [AUC] 0.685, 95% confidence interval [CI] 0.616–0.754, p = 0.039; pTau/tTau ratio: AUC 0.777, 95% CI 0.707–0.848, p < 0.001). Among ALS patients, increased tTau levels were associated with advanced age of onset, increased revised amyotrophic lateral sclerosis functional rating scale (ALSFRS‐R) score (ΔFS) rate of progression, and spinal onset. Multivariate analysis showed that in ALS patients, this biomarker was an independent negative predictor of overall survival.ConclusionsOur findings suggest that tTau and pTau/tTau ratio can be diagnostic biomarkers of ALS. In addition, CSF tTau level at diagnosis might play a relevant prognostic role in the disease.
Disentangling complexity of fishing fleets: using sequence analysis to classify distinguishable groups of vessels based on commercial landings
Authors: Meyer Steffi , Krumme Uwe 
Published: February 2021

AbstractCapturing the diversity of fishing fleets and identifying distinct subgroups is essential for effectively directing research and management efforts. In this study, the German Baltic gillnet fleet was split into distinguishable groups of vessels by applying a stepwise approach. Monthly landing profiles were classified using clustering techniques and arranged as annual landing sequences, as the basis to form groups of vessels with distinct annual landing sequences using sequence analysis. Commercial landings from 1243 vessels across 11 years (2008–2018) resulted in 8031 annual landing sequences, which were clustered into eight groups, each with a characteristic, annually recurring, seasonal landing pattern (cod group, cod‐herring group, herring‐flounder group, herring group, freshwater fish group, pikeperch group, eel group and port group). The results highlight the heterogeneity of the fleet and a strong adaptation to regional and seasonal resource availability. Studying sequences of landings instead of isolated events in time provides insight into the interlinkage and succession of landings and can aid at classifying fishing fleets and better targeting groups of vessels of interest.