bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9
Authors: Zeitlinger Markus , Bauer Martin , Reindl-Schwaighofer Roman , Stoekenbroek Robert M. , Lambert Gilles , Berger-Sieczkowski Evelyn , Lagler Heimo , Oesterreicher Zoe , Wulkersdorfer Beatrix , Lührs Petra , Galabova Gergana , Schwenke Carsten , Mader Robert M. , Medori Rossella , Landlinger Christine , Kutzelnigg Alexandra , Staffler Günther 
Published: May 2021

Abstract
Purpose
AT04A and AT06A are two AFFITOPE® peptide vaccine candidates being developed for the treatment of hypercholesterolemia by inducing proprotein convertase subtilisin/kexin type 9 (PCSK9)-specific antibodies. This study aimed to investigate safety, tolerability, antibody development, and reduction of low-density lipoprotein cholesterol (LDLc) following four subcutaneous immunizations.

Methods
This phase I, single-blind, randomized, placebo-controlled study was conducted in a total of 72 healthy subjects with a mean fasting LDLc level at baseline of 117.1 mg/dL (range 77–196 mg/dL). Each cohort enrolled 24 subjects to receive three priming immunizations at weeks 0, 4, and 8 and to receive a single booster immunization at week 60 of either AT04A, AT06A, or placebo. In addition to safety (primary objective), the antigenic peptide- and PCSK9-specific antibody response and the impact on LDLc were evaluated over a period of 90 weeks.

Results
The most common systemic treatment-related adverse events (AEs) reported were fatigue, headache, and myalgia in 75% of subjects in the AT06A group and 58% and 46% of subjects in the placebo and AT04A groups, respectively. Injection site reactions (ISR) representing 63% of all treatment-emergent adverse events (TEAEs), were transient and mostly of mild or moderate intensity and rarely severe (3%). Both active treatments triggered a robust, long-lasting antibody response towards the antigenic peptides used for immunization that optimally cross-reacted with the target epitope on PCSK9. In the AT04A group, a reduction in serum LDLc was observed with a mean peak reduction of 11.2% and 13.3% from baseline compared to placebo at week 20 and 70 respectively, and over the whole study period, the mean LDLc reduction for the AT04A group vs. placebo was −7.2% (95% CI [−10.4 to −3.9], P < 0.0001). In this group, PCSK9 target epitope titers above 50 were associated with clinically relevant LDLc reductions with an individual maximal decrease of 39%.

Conclusions
Although both AT04A and AT06 were safe and immunogenic, only AT04A demonstrated significant LDLc-lowering activity, justifying further development.

Trial registration
EudraCT: 2015-001719-11. ClinicalTrials.gov
Identifier: NCT02508896.
Studies of the seasonal prediction of heavy late spring rainfall over southeastern China
Authors: Zhang Shouwen , Wang Hui , Jiang Hua , Ma Wentao 
Published: May 2021

AbstractThe late spring rainfall may account for 15% of the annual total rainfall, which is crucial to early planting in southeastern China. A better understanding of the precipitation variations in the late spring and its predictability not only greatly increase our knowledge of related mechanisms, but it also benefits society and the economy. Four models participating in the North American Multi-Model Ensemble (NMME) were selected to study their abilities to forecast the late spring rainfall over southeastern China and the major sources of heavy rainfall from the perspective of the sea surface temperature (SST) field. We found that the models have better abilities to forecast the heavy rainfall over the middle and lower reaches of the Yangtze River region (MLYZR) with only a 1-month lead time, but they failed for a 3-month lead time since the occurrence of the heavy rainfall was inconsistent with the observations. The observations indicate that the warm SST anomalies in the tropical eastern Indian Ocean are vital to the simultaneously heavy rainfall in the MLYZR in May, but an El Niño event is not a necessary condition for determining the heavy rainfall over the MLYZR. The heavy rainfall over the MLYZR in May is always accompanied by warming of the northeastern Indian Ocean and of the northeastern South China Sea (NSCS) from April to May in the models and observations, respectively. In the models, El Niño events may promote the warming processes over the northeastern Indian Ocean, which leads to heavy rainfall in the MLYZR. However, in the real world, El Niño events are not the main reason for the warming of the NSCS, and further research on the causes of this warming is still needed.
Machine learning classifier to identify clinical and radiological features relevant to disability progression in multiple sclerosis
Authors: Tommasin Silvia , Cocozza Sirio , Taloni Alessandro , Giannì Costanza , Petsas Nikolaos , Pontillo Giuseppe , Petracca Maria , Ruggieri Serena , De Giglio Laura , Pozzilli Carlo , Brunetti Arturo , Pantano Patrizia 
Published: May 2021

AbstractObjectivesTo evaluate the accuracy of a data-driven approach, such as machine learning classification, in predicting disability progression in MS.MethodsWe analyzed structural brain images of 163 subjects diagnosed with MS acquired at two different sites. Participants were followed up for 2–6 years, with disability progression defined according to the expanded disability status scale (EDSS) increment at follow-up. T2-weighted lesion load (T2LL), thalamic and cerebellar gray matter (GM) volumes, fractional anisotropy of the normal appearing white matter were calculated at baseline and included in supervised machine learning classifiers. Age, sex, phenotype, EDSS at baseline, therapy and time to follow-up period were also included. Classes were labeled as stable or progressed disability. Participants were randomly chosen from both sites to build a sample including 50% patients showing disability progression and 50% patients being stable. One-thousand machine learning classifiers were applied to the resulting sample, and after testing for overfitting, classifier confusion matrix, relative metrics and feature importance were evaluated.ResultsAt follow-up, 36% of participants showed disability progression. The classifier with the highest resulting metrics had accuracy of 0.79, area under the true positive versus false positive rates curve of 0.81, sensitivity of 0.90 and specificity of 0.71. T2LL, thalamic volume, disability at baseline and administered therapy were identified as important features in predicting disability progression. Classifiers built on radiological features had higher accuracy than those built on clinical features.ConclusionsDisability progression in MS may be predicted via machine learning classifiers, mostly evaluating neuroradiological features.
Ligation of the middle hepatic vein to increase hypertrophy induction during the ALPPS procedure
Authors: Dondorf F. , Deeb A. Ali , Bauschke A. , Felgendreff P. , Tautenhahn H. M. , Ardelt M. , Settmacher U. , Rauchfuss F. 
Published: May 2021

Abstract
Purpose
Here, we analyse the technical modification of the ALPPS procedure, ligating the middle hepatic vein during the first step of the operation to enhance remnant liver hypertrophy.

Methods
In 20 of 37 ALPPS procedures, the middle hepatic vein was ligated during the first step. Hypertrophy of the functional remnant liver volume was assessed in addition to postoperative courses.

Results
Volumetric analysis showed a significant volume increase, especially for patients with colorectal metastases. Pre-existing liver parenchyma damage (odds ratio = 0.717, p = 0.017) and preoperative chemotherapy were found to be significant predictors (odds ratio = 0.803, p = 0.045) of higher morbidity and mortality. In addition, a survival benefit for maintenance of middle hepatic vein was shown.

Conclusion
This technical modification of the ALPPS procedure can accentuate future liver remnant volume hypertrophy. The higher morbidity and mortality observed are most likely associated with pre-existing parenchymal damage within this group.
Irregular Tilings of Regular Polygons with Similar Triangles
Authors: Laczkovich Miklos 
Published: May 2021

AbstractWe say that a triangle T tiles a polygon A, if A can be dissected into finitely many nonoverlapping triangles similar to T. We show that if $$N>42$$

N
>
42

, then there are at most three nonsimilar triangles T such that the angles of T are rational multiples of $$\pi $$
π
and T tiles the regular N-gon. A tiling into similar triangles is called regular, if the pieces have two angles, $$\alpha $$
α
and $$\beta $$
β
, such that at each vertex of the tiling the number of angles $$\alpha $$
α
is the same as that of $$\beta $$
β
. Otherwise the tiling is irregular. It is known that for every regular polygon A there are infinitely many triangles that tile A regularly. We show that if $$N>10$$

N
>
10

, then a triangle T tiles the regular N-gon irregularly only if the angles of T are rational multiples of $$\pi $$
π
. Therefore, the number of triangles tiling the regular N-gon irregularly is at most three for every $$N>42$$

N
>
42

.
A Choosing Wisely top-5 list to support general practitioners in Austria
Authors: Glechner Anna , Rabady Susanne , Bachler Herbert , Dachs Christoph , Flamm Maria , Glehr Reinhold , Hoffmann Kathryn , Hoffmann-Dorninger Renate , Kamenski Gustav , Lutz Matthias , Poggenburg Stephanie , Tschiggerl Wilfried , Horvath Karl 
Published: May 2021

SummaryFrom a pool of 147 reliable recommendations, ten experts from the Austrian Society of General Practice and Family Medicine selected 21 relevant recommendations as the basis for the Delphi process. In two Delphi rounds, eleven experts established a top‑5 list of recommendations designed for Austrian family practice to reduce medical overuse. Three of the chosen recommendations address the issue of antibiotic usage in patients with viral upper respiratory tract infections, in children with mild otitis media, and in patients with asymptomatic bacteriuria. The other two “do not do” recommendations concern imaging studies for nonspecific low back pain and routine screening to detect prostate cancer. A subsequent survey identified the reasons for selecting these top‑5 recommendations: the frequency of the issue, potential harms, costs, and patients’ expectations. Experts hope the campaign will save time in educating patients and provide legal protection for omitting measures.
Vibration characteristics of piezoelectric functionally graded carbon nanotube-reinforced composite doubly-curved shells
Authors: Tham V. V. , Tran H. Q. , Tu T. M. 
Published: May 2021

AbstractThis paper presents an analytical solution for the free vibration behavior of functionally graded carbon nanotube-reinforced composite (FG-CNTRC) doubly curved shallow shells with integrated piezoelectric layers. Here, the linear distribution of electric potential across the thickness of the piezoelectric layer and five different types of carbon nanotube (CNT) distributions through the thickness direction are considered. Based on the four-variable shear deformation refined shell theory, governing equations are obtained by applying Hamilton’s principle. Navier’s solution for the shell panels with the simply supported boundary condition at all four edges is derived. Several numerical examples validate the accuracy of the presented solution. New parametric studies regarding the effects of different material properties, shell geometric parameters, and electrical boundary conditions on the free vibration responses of the hybrid panels are investigated and discussed in detail.
Observations on recent mass mortality events of marine mussels in the Oosterschelde, the Netherlands
Authors: Capelle Jacob J. , Garcia Ainhoa Blanco , Kamermans Pauline , Engelsma Marc Y. , Jansen Henrice M. 
Published: May 2021

AbstractTwo mass mortality events (MMEs) of marine mussels that took place in the Oosterschelde, the Netherlands—the first in 2015/2016 and the second in 2019—both severely affected mussel production. The current study presents our observations on the onset and course of both MMEs and discusses probable putative causes. The two MMEs displayed a distinct course of events. The first event started in November 2015 with high mortality rates on culture plots, which remained elevated until the autumn of 2016. Approximately 40–50% of mussels from all age classes were lost on culture plots and 100% were lost from wild seed beds. The second event started in April–May 2019 and continued until the end of July, with mortality ranging from 20 to 100%, again from all age classes. Culture areas other than the Oosterschelde and other shellfish species were not affected. Histological and bacteriological screening produced no evidence for common pathogens or pollution as a primary mortality factor and there is no indication of abnormal environmental conditions preceding or during the events. We hypothesize that a cumulation of stressors results in weakening of the mussels and in elevated mortality rates. In 2019, this cumulation of stressors could be high spawning activities (an unusual high concentration of mussel larvae was found in April) that resulted in very low condition from April to June, a Phaeocystis bloom in April to May that prevented a quick recovery, and the development of granulocytomas that were found in up to 60 to 70% of live mussels as a consequence of cumulative stress. Although no (single) putative causes could be identified, this study contributes to the knowledge on MMEs in mussels and fits in a wider and disturbing trend on mortality events in shellfish.
Bird communities in a degraded forest biodiversity hotspot of East Africa
Authors: Mulwa Moses , Teucher Mike , Ulrich Werner , Habel Jan Christian 
Published: May 2021

AbstractTropical forests suffer severe habitat destruction. Thus, tropical forests frequently consist today of only a few small remnants that are often embedded within a matrix of agricultural fields and tree plantations. Forest specialist species have experienced severe population declines under these circumstances. We studied bird communities based on census plots set up in a near-natural forest block, as well as degraded forest patches, tree plantations, and agricultural fields, across the Taita Hills in southern Kenya. We classified each bird species according its ecology and behavior. We quantified the land cover and landscape configuration around each census plot. Typical forest species were mainly observed in the near-natural forest block, and to a lower extent in degraded forest patches. Plantations were almost devoid of birds. Bird communities of small forest fragments were more similar to that of agricultural land than the near-natural forest block. Most frugivorous, insectivorous and nectarivorous birds occurred in forest habitats, while granivorous bird species dominated the bird communities of agricultural land. The surrounding landscape had a marginal impact on bird species composition at local sites. Our study showed that the preservation of near-natural cloud forest, including small forest patches, is essential for the conservation of forest-dependent species, and that plantations do not serve as surrogate habitats.
On the Role of Bilateral Brain Hypofunction and Abnormal Lateralization of Cortical Information Flow as Neural Underpinnings of Conventional Metaphor Processing Impairment in Schizophrenia: An fMRI and EEG Study
Authors: Adamczyk Przemysław , Jáni Martin , Ligeza Tomasz S. , Płonka Olga , Błądziński Piotr , Wyczesany Miroslaw 
Published: May 2021

AbstractFigurative language processing (e.g. metaphors) is commonly impaired in schizophrenia. In the present study, we investigated the neural activity and propagation of information within neural circuits related to the figurative speech, as a neural substrate of impaired conventional metaphor processing in schizophrenia. The study included 30 schizophrenia outpatients and 30 healthy controls, all of whom were assessed with a functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG) punchline-based metaphor comprehension task including literal (neutral), figurative (metaphorical) and nonsense (absurd) endings. The blood oxygenation level-dependent signal was recorded with 3T MRI scanner and direction and strength of cortical information flow in the time course of task processing was estimated with a 64-channel EEG input for directed transfer function. The presented results revealed that the behavioral manifestation of impaired figurative language in schizophrenia is related to the hypofunction in the bilateral fronto-temporo-parietal brain regions (fMRI) and various differences in effective connectivity in the fronto-temporo-parietal circuit (EEG). Schizophrenia outpatients showed an abnormal pattern of connectivity during metaphor processing which was related to bilateral (but more pronounced at the left hemisphere) hypoactivation of the brain. Moreover, we found reversed lateralization patterns, i.e. a rightward-shifted pattern during metaphor processing in schizophrenia compared to the control group. In conclusion, the presented findings revealed that the impairment of the conventional metaphor processing in schizophrenia is related to the bilateral brain hypofunction, which supports the evidence on reversed lateralization of the language neural network and the existence of compensatory recruitment of alternative neural circuits in schizophrenia.
Pathways and pitfalls in extreme event attribution
Authors: van Oldenborgh Geert Jan , van der Wiel Karin , Kew Sarah , Philip Sjoukje , Otto Friederike , Vautard Robert , King Andrew , Lott Fraser , Arrighi Julie , Singh Roop , van Aalst Maarten 
Published: May 2021

AbstractThe last few years have seen an explosion of interest in extreme event attribution, the science of estimating the influence of human activities or other factors on the probability and other characteristics of an observed extreme weather or climate event. This is driven by public interest, but also has practical applications in decision-making after the event and for raising awareness of current and future climate change impacts. The World Weather Attribution (WWA) collaboration has over the last 5 years developed a methodology to answer these questions in a scientifically rigorous way in the immediate wake of the event when the information is most in demand. This methodology has been developed in the practice of investigating the role of climate change in two dozen extreme events world-wide. In this paper, we highlight the lessons learned through this experience. The methodology itself is documented in a more extensive companion paper. It covers all steps in the attribution process: the event choice and definition, collecting and assessing observations and estimating probability and trends from these, climate model evaluation, estimating modelled hazard trends and their significance, synthesis of the attribution of the hazard, assessment of trends in vulnerability and exposure, and communication. Here, we discuss how each of these steps entails choices that may affect the results, the common problems that can occur and how robust conclusions can (or cannot) be derived from the analysis. Some of these developments also apply to other attribution methodologies and indeed to other problems in climate science.
Heat vulnerability and adaptive capacities: findings of a household survey in Ludwigsburg, BW, Germany
Authors: Laranjeira Kevin , Göttsche Franziska , Birkmann Joern , Garschagen Matthias 
Published: May 2021

AbstractIn 2019, record-setting temperatures in Europe adversely affected human health and wellbeing (WMO 2020) and cities—thus, people in urban areas suffered particularly under heat stress. However, not only heat stress but also the differential vulnerability of people exposed is key when defining adaptation priorities. Up to now, local data on vulnerability and particularly adaptive capacities is rather rare. Various aspects of human vulnerability to heat and capacities to adapt to heat stress in urban areas still have to be explored and assessed, for example in terms of the adaptation at home, during work or while commuting to work. The paper presents new findings of a household survey on how and where different groups experience heat stress and how they assess their susceptibility and capacities to cope and adapt. The findings are based on a survey conducted in the medium-sized city of Ludwigsburg, Germany. Findings show significant linkages and correlations between socio-economic factors and heat vulnerability and capacities to respond. The analysis gives special emphasis to relationships between willingness to implement adaptive measures to reduce heat stress risks and risk perception and adaptive capacities. Particularly, the analysis of future adaptation options and the ability and willingness of different households to implement these provides new insights on the differential capacities to adapt and the need for tailor-made transformation programs.
Mobility, ecotoxicity, bioaccumulation and sources of trace elements in the bottom sediments of the Rożnów reservoir
Authors: Szara-Bąk Magdalena , Baran Agnieszka , Klimkowicz-Pawlas Agnieszka , Tkaczewska Joanna , Wojtasik Barbara 
Published: May 2021

AbstractThe aim of the study was to use of geochemical, chemical, ecotoxicological and biological indicators for a comprehensive assessment of ecological risks related to the mobility, ecotoxicity and bioavailability of trace elements in the bottom sediment of the Rożnów reservoir. The study found three elements deserving attention in the sediments: cadmium, nickel and chromium. Cadmium proved to be the most mobile and bioavailable, although the total cadmium content and geochemical indicators did not reveal any risk to organisms. Geochemical indicators showed that the sediments are contaminated with nickel and chromium, but both elements had a low bioaccumulation factor. Fractional analysis also revealed relatively low mobility of Cr and Ni and a higher potential risk of bioavailability for nickel. Most of the tested sediment samples had low toxicity in relation to the tested organisms. For H. incongruens, 11% of the samples were non-toxic, 50% of the samples had low toxicity, and 39% of the samples were toxic. For A. fischeri, no toxicity was found in 7% of the samples, low toxicity in 76% of the samples and toxicity in 17% of the sediment samples. The As, Cd, Cu content in the F1 fraction correlated significantly positively with the content of these metals in mussel tissues. Both biotesting and chemical analysis can reveal a potential risk to aquatic organisms. For a real assessment of the ecological risks associated with trace elements, it is necessary to use bioindicators taken from the environment and exposed to trace elements in situ.