bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemoprotective antimalarials identified through quantitative high-throughput screening of Plasmodium blood and liver stage parasites
Authors: Dorjsuren Dorjbal , Eastman Richard T. , Wicht Kathryn J. , Jansen Daniel , Talley Daniel C. , Sigmon Benjamin A. , Zakharov Alexey V. , Roncal Norma , Girvin Andrew T. , Antonova-Koch Yevgeniya , Will Paul M. , Shah Pranav , Sun Hongmao , Klumpp-Thomas Carleen , Mok Sachel , Yeo Tomas , Meister Stephan , Marugan Juan Jose , Ross Leila S. , Xu Xin , Maloney David J. , Jadhav Ajit , Mott Bryan T. , Sciotti Richard J. , Winzeler Elizabeth A. , Waters Norman C. , Campbell Robert F. , Huang Wenwei , Simeonov Anton , Fidock David A. 
Published: January 2021

AbstractThe spread of Plasmodium falciparum parasites resistant to most first-line antimalarials creates an imperative to enrich the drug discovery pipeline, preferably with curative compounds that can also act prophylactically. We report a phenotypic quantitative high-throughput screen (qHTS), based on concentration–response curves, which was designed to identify compounds active against Plasmodium liver and asexual blood stage parasites. Our qHTS screened over 450,000 compounds, tested across a range of 5 to 11 concentrations, for activity against Plasmodium falciparum asexual blood stages. Active compounds were then filtered for unique structures and drug-like properties and subsequently screened in a P. berghei liver stage assay to identify novel dual-active antiplasmodial chemotypes. Hits from thiadiazine and pyrimidine azepine chemotypes were subsequently prioritized for resistance selection studies, yielding distinct mutations in P. falciparum cytochrome b, a validated antimalarial drug target. The thiadiazine chemotype was subjected to an initial medicinal chemistry campaign, yielding a metabolically stable analog with sub-micromolar potency. Our qHTS methodology and resulting dataset provides a large-scale resource to investigate Plasmodium liver and asexual blood stage parasite biology and inform further research to develop novel chemotypes as causal prophylactic antimalarials.
Anatomical and ontogenetic influences on muscle density
Authors: Leonard Kaitlyn C. , Worden Nikole , Boettcher Marissa L. , Dickinson Edwin , Omstead Kailey M. , Burrows Anne M. , Hartstone-Rose Adam 
Published: January 2021

AbstractPhysiological cross-sectional area (PCSA), an important biomechanical variable, is an estimate of a muscle’s contractile force potential and is derived from dividing muscle mass by the product of a muscle’s average fascicle length and a theoretical constant representing the density of mammalian skeletal muscle. This density constant is usually taken from experimental studies of small samples of several model taxa using tissues collected predominantly from the lower limbs of adult animals. The generalized application of this constant to broader analyses of mammalian myology assumes that muscle density (1) is consistent across anatomical regions and (2) is unaffected by the aging process. To investigate the validity of these assumptions, we studied muscles of rabbits (Oryctolagus cuniculus) in the largest sample heretofore investigated explicitly for these variables, and we did so from numerous anatomical regions and from three different age-cohorts. Differences in muscle density and histology as a consequence of age and anatomical region were evaluated using Tukey’s HSD tests. Overall, we observed that older individuals tend to have denser muscles than younger individuals. Our findings also demonstrated significant differences in muscle density between anatomic regions within the older cohorts, though none in the youngest cohort. Approximately 50% of the variation in muscle density can be explained histologically by the average muscle fiber area and the average percent fiber area. That is, muscles with larger average fiber areas and a higher proportion of fiber area tend to be denser. Importantly, using the age and region dependent measurements of muscle density that we provide may increase the accuracy of PCSA estimations. Although we found statistically significant differences related to ontogeny and anatomical region, if density cannot be measured directly, the specific values presented herein should be used to improve accuracy. If a single muscle density constant that has been better validated than the ones presented in the previous literature is preferred, then 1.0558 and 1.0502 g/cm3 would be reasonable constants to use across all adult and juvenile muscles respectively.
Post-conception heat exposure increases clinically unobserved pregnancy losses
Authors: Hajdu Tamás , Hajdu Gábor 
Published: January 2021

AbstractEvidence of the relationship between temperature during pregnancy and human embryo mortality is limited. Most importantly, the literature lacks causal estimations and studies on early pregnancy losses. Here, we estimate the impact of early pregnancy temperature exposure on the clinically unobserved pregnancy loss rate. We use administrative data of clinically observed pregnancies from more than three decades for Hungary. We apply an empirical approach that allows us to infer the impact of temperature on the clinically unobserved pregnancy loss rate from the estimated effects on the clinically observed conception rate. The results show that exposure to hot temperatures during the first few weeks after the conception week increases the clinically unobserved pregnancy loss rate, whereas exposure to colder temperatures seems to decrease it. Importantly, the temperature-induced changes represent changes in the total number of pregnancy losses rather than a compositional change between clinically observed and clinically unobserved pregnancy losses.
Headache and musculoskeletal pain in school children are associated with uncorrected vision problems and need for glasses: a case–control study
Authors: Thorud Hanne-Mari Schiøtz , Aurjord Rakel , Falkenberg Helle K. 
Published: January 2021

AbstractMusculoskeletal pain and headache are leading causes of years lived with disability, and an escalating problem in school children. Children spend increasingly more time reading and using digital screens, and increased near tasks intensify the workload on the precise coordination of the visual and head-stabilizing systems. Even minor vision problems can provoke headache and neck- and shoulder (pericranial) pain. This study investigated the association between headaches, pericranial tenderness, vision problems, and the need for glasses in children. An eye and physical examination was performed in twenty 10–15 year old children presenting to the school health nurse with headache and pericranial pain (pain group), and twenty age-and-gender matched classmates (control group). The results showed that twice as many children in the pain group had uncorrected vision and needed glasses. Most children were hyperopic, and glasses were recommended mainly for near work. Headache and pericranial tenderness were significantly correlated to reduced binocular vision, reduced distance vision, and the need for new glasses. That uncorrected vision problems are related to upper body musculoskeletal symptoms and headache, indicate that all children with these symptoms should have a full eye examination to promote health and academic performance.
Effects of open-label placebos on test performance and psychological well-being in healthy medical students: a randomized controlled trial
Authors: Kleine-Borgmann Julian , Schmidt Katharina , Billinger Marieke , Forkmann Katarina , Wiech Katja , Bingel Ulrike 
Published: January 2021

AbstractPsychological distress is prevalent in students and can predispose to psychiatric disorders. Recent findings indicate that distress might be linked to impaired cognitive performance in students. Experimental findings in healthy participants suggest that placebo interventions can improve cognition. However, whether non-deceptive (i.e., open-label, OLP) placebos can enhance cognitive function and emotional well-being is unclear. Using a randomized-controlled design we demonstrate a positive impact of OLP on subjective well-being (i.e., stress, fatigue, and confusion) after a 21-day OLP application in healthy students during midterm exams. OLP did not improve test performance, but, within the OLP group, test performance was positively correlated with measures of general belief in the benefit of medication. These results show that OLP can counteract negative effects of acute stress on psychological well-being and might improve cognitive performance if supported by positive treatment expectations. Additionally, our findings in healthy volunteers warrant further investigation in exploring the potential of OLP in reducing stress-related psychological effects in patients. The trial was preregistered at the German Clinical Trials Register on December 20, 2017 (DRKS00013557).
Deep learning predicts postsurgical recurrence of hepatocellular carcinoma from digital histopathologic images
Authors: Yamashita Rikiya , Long Jin , Saleem Atif , Rubin Daniel L. , Shen Jeanne 
Published: January 2021

AbstractRecurrence risk stratification of patients undergoing primary surgical resection for hepatocellular carcinoma (HCC) is an area of active investigation, and several staging systems have been proposed to optimize treatment strategies. However, as many as 70% of patients still experience tumor recurrence at 5 years post-surgery. We developed and validated a deep learning-based system (HCC-SurvNet) that provides risk scores for disease recurrence after primary resection, directly from hematoxylin and eosin-stained digital whole-slide images of formalin-fixed, paraffin embedded liver resections. Our model achieved concordance indices of 0.724 and 0.683 on the internal and external test cohorts, respectively, exceeding the performance of the standard Tumor-Node-Metastasis classification system. The model’s risk score stratified patients into low- and high-risk subgroups with statistically significant differences in their survival distributions, and was an independent risk factor for post-surgical recurrence in both test cohorts. Our results suggest that deep learning-based models can provide recurrence risk scores which may augment current patient stratification methods and help refine the clinical management of patients undergoing primary surgical resection for HCC.
Mixture model investigation of the inner–outer asymmetry in visual crowding reveals a heavier weight towards the visual periphery
Authors: Shechter Adi , Yashar Amit 
Published: January 2021

AbstractCrowding, the failure to identify a peripheral item in clutter, is an essential bottleneck in visual information processing. A hallmark characteristic of crowding is the inner–outer asymmetry in which the outer flanker (more eccentric) produces stronger interference than the inner one (closer to the fovea). We tested the contribution of the inner-outer asymmetry to the pattern of crowding errors in a typical radial crowding display in which both flankers are presented simultaneously on the horizontal meridian. In two experiments, observers were asked to estimate the orientation of a Gabor target. Instead of the target, observers reported the outer flanker much more frequently than the inner one. When the target was the outer Gabor, crowding was reduced. Furthermore, when there were four flankers, two on each side of the target, observers misreported the outer flanker adjacent to the target, not the outermost flanker. Model comparisons suggested that orientation crowding reflects sampling over a weighted sum of the represented features, in which the outer flanker is more heavily weighted compared to the inner one. Our findings reveal a counterintuitive phenomenon: in a radial arrangement of orientation crowding, within a region of selection, the outer item dominates appearance more than the inner one.
A combined convolutional and recurrent neural network for enhanced glaucoma detection
Authors: Gheisari Soheila , Shariflou Sahar , Phu Jack , Kennedy Paul J. , Agar Ashish , Kalloniatis Michael , Golzan S. Mojtaba 
Published: January 2021

AbstractGlaucoma, a leading cause of blindness, is a multifaceted disease with several patho-physiological features manifesting in single fundus images (e.g., optic nerve cupping) as well as fundus videos (e.g., vascular pulsatility index). Current convolutional neural networks (CNNs) developed to detect glaucoma are all based on spatial features embedded in an image. We developed a combined CNN and recurrent neural network (RNN) that not only extracts the spatial features in a fundus image but also the temporal features embedded in a fundus video (i.e., sequential images). A total of 1810 fundus images and 295 fundus videos were used to train a CNN and a combined CNN and Long Short-Term Memory RNN. The combined CNN/RNN model reached an average F-measure of 96.2% in separating glaucoma from healthy eyes. In contrast, the base CNN model reached an average F-measure of only 79.2%. This proof-of-concept study demonstrates that extracting spatial and temporal features from fundus videos using a combined CNN and RNN, can markedly enhance the accuracy of glaucoma detection.
Development and large volume production of extremely high current density YBa2Cu3O7 superconducting wires for fusion
Authors: Molodyk A. , Samoilenkov S. , Markelov A. , Degtyarenko P. , Lee S. , Petrykin V. , Gaifullin M. , Mankevich A. , Vavilov A. , Sorbom B. , Cheng J. , Garberg S. , Kesler L. , Hartwig Z. , Gavrilkin S. , Tsvetkov A. , Okada T. , Awaji S. , Abraimov D. , Francis A. , Bradford G. , Larbalestier D. , Senatore C. , Bonura M. , Pantoja A. E. , Wimbush S. C. , Strickland N. M. , Vasiliev A. 
Published: January 2021

AbstractThe fusion power density produced in a tokamak is proportional to its magnetic field strength to the fourth power. Second-generation high temperature superconductor (2G HTS) wires demonstrate remarkable engineering current density (averaged over the full wire), JE, at very high magnetic fields, driving progress in fusion and other applications. The key challenge for HTS wires has been to offer an acceptable combination of high and consistent superconducting performance in high magnetic fields, high volume supply, and low price. Here we report a very high and reproducible JE in practical HTS wires based on a simple YBa2Cu3O7 (YBCO) superconductor formulation with Y2O3 nanoparticles, which have been delivered in just nine months to a commercial fusion customer in the largest-volume order the HTS industry has seen to date. We demonstrate a novel YBCO superconductor formulation without the c-axis correlated nano-columnar defects that are widely believed to be prerequisite for high in-field performance. The simplicity of this new formulation allows robust and scalable manufacturing, providing, for the first time, large volumes of consistently high performance wire, and the economies of scale necessary to lower HTS wire prices to a level acceptable for fusion and ultimately for the widespread commercial adoption of HTS.
Association between triglyceride glucose index and peak growth hormone in children with short stature
Authors: Zhao Qianqian , Chu Yuntian , Pan Hui , Zhang Mei , Ban Bo 
Published: January 2021

AbstractGrowth hormone (GH) secretion is related to many factors, such as weight and puberty, and the reproducibility of GH provocation tests is very poor. This study aimed to evaluate whether the triglyceride (TyG) index was associated with peak GH in children with short stature. This study included 1095 children with short stature divided into two groups based on peak GH level in GH provocation tests [GH deficiency (GHD) group = 733 children; non-GHD group = 362 children]. We found that the TyG index was significantly higher in the GHD group than in the non-GHD group (P < 0.001). A nonlinear relationship was detected between the TyG index and peak GH, whose point was 7.8. A significant negative association between the TyG index and peak GH was observed when the TyG index was greater than 7.8 (β − 2.61, 95% CI − 3.98, − 1.24;P < 0.001), whereas, the relationship between the TyG index and peak GH was not significant when the TyG index was lower than 7.8 (β 0.25, 95% CI − 1.68, 2.17;P = 0.799). There is a nonlinear relationship between the TyG index and peak GH, and a higher TyG index is associated with decreased peak GH in children with short stature.
Genetic deletion of Abcc6 disturbs cholesterol homeostasis in mice
Authors: Ibold Bettina , Tiemann Janina , Faust Isabel , Ceglarek Uta , Dittrich Julia , Gorgels Theo G. M. F. , Bergen Arthur A. B. , Vanakker Olivier , Van Gils Matthias , Knabbe Cornelius , Hendig Doris 
Published: January 2021

AbstractGenetic studies link adenosine triphosphate-binding cassette transporter C6 (ABCC6) mutations to pseudoxanthoma elasticum (PXE).ABCC6 sequence variations are correlated with altered HDL cholesterol levels and an elevated risk of coronary artery diseases. However, the role of ABCC6 in cholesterol homeostasis is not widely known. Here, we report reduced serum cholesterol and phytosterol levels in Abcc6-deficient mice, indicating an impaired sterol absorption. Ratios of cholesterol precursors to cholesterol were increased, confirmed by upregulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) expression, suggesting activation of cholesterol biosynthesis inAbcc6−/−mice. We found that cholesterol depletion was accompanied by a substantial decrease in HDL cholesterol mediated by lowered ApoA-I and ApoA-II protein levels and not by inhibited lecithin-cholesterol transferase activity. Additionally, higher proprotein convertase subtilisin/kexin type 9 (Pcsk9) serum levels inAbcc6−/−mice and PXE patients and elevated ApoB level in knockout mice were observed, suggesting a potentially altered very low-density lipoprotein synthesis. Our results underline the role of Abcc6 in cholesterol homeostasis and indicate impaired cholesterol metabolism as an important pathomechanism involved in PXE manifestation.
Simple design of efficient broadband multifunctional polarization converter for X-band applications
Authors: Nguyen Thi Kim Thu , Nguyen Thi Minh , Nguyen Hong Quang , Cao Thanh Nghia , Le Dac Tuyen , Bui Xuan Khuyen , Bui Son Tung , Truong Chi Lam , Vu Dinh Lam , Nguyen Thi Quynh Hoa 
Published: January 2021

AbstractA simple design of a broadband multifunctional polarization converter using an anisotropic metasurface for X-band application is proposed. The proposed polarization converter consists of a periodic array of the two-corner-cut square patch resonators based on the FR-4 substrate that achieves both cross-polarization and linear-to-circular polarization conversions. The simulated results show that the polarization converter displays the linear cross-polarization conversion in the frequency range from 8 to 12 GHz with the polarization conversion efficiency above 90%. The efficiency is kept higher than 80% with wide incident angle up to 45°. Moreover, the proposed design achieves the linear-to-circular polarization conversion at two frequency bands of 7.42–7.6 GHz and 13–13.56 GHz. A prototype of the proposed polarization converter is fabricated and measured, showing a good agreement between the measured and simulated results. The proposed polarization converter exhibits excellent performances such as simple structure, multifunctional property, and large cost-efficient bandwidth and wide incident angle insensitivity in the linear cross polarization conversion, which can be useful for X-band applications. Furthermore, this structure can be extended to design broadband polarization converters in other frequency bands.
Correlation between fundus autofluorescence and visual function in patients with cone-rod dystrophy
Authors: Kanda Satoru , Hara Takumi , Fujino Ryosuke , Azuma Keiko , Soga Hirotsugu , Asaoka Ryo , Obata Ryo , Inoue Tatsuya 
Published: January 2021

AbstractThis study aimed to investigate the relationship between autofluorescence (AF) signal measured with ultra-wide field imaging and visual functions in patients with cone-rod dystrophy (CORD). A retrospective chart review was performed for CORD patients. We performed the visual field test and fundus autofluorescence (FAF) measurement and visualized retinal structures with optical coherence tomography (OCT) on the same day. Using binarised FAF images, we identified a low FAF area ratio (LFAR: low FAF/30°). Relationships between age and logMAR visual acuity (VA), central retinal thickness (CRT), central choroidal thickness (CCT), mean deviation (MD) value, and LFAR were investigated. Thirty-seven eyes of 21 CORD patients (8 men and 13 women) were enrolled. The mean patient age was 49.8 years. LogMAR VA and MD were 0.52 ± 0.47 and − 17.91 ± 10.59 dB, respectively. There was a significant relationship between logMAR VA and MD (p = 0.001). LogMAR VA significantly correlated with CRT (p = 0.006) but not with other parameters. Conversely, univariate analysis suggested a significant relationship between MD and LFAR (p = 0.001). In the multivariate analysis, LFAR was significantly associated with MD (p = 0.002). In conclusion, it is useful to measure the low FAF area in patients with CORD. The AF measurement reflects the visual field deterioration but not VA in CORD.
Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis
Authors: Conti Elisa , Sala Gessica , Diamanti Susanna , Casati Marco , Lunetta Christian , Gerardi Francesca , Tarlarini Claudia , Mosca Lorena , Riva Nilo , Falzone Yuri , Filippi Massimo , Appollonio Ildebrando , Ferrarese Carlo , Tremolizzo Lucio 
Published: January 2021

AbstractAmyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in serum, wherein cognate naturally-occurring auto-antibodies (anti-TDP-43 NAb) might be also present, albeit they have never been documented before. In this exploratory study, we quantified the levels of both anti-TDP-43 NAb and TDP-43 protein as putative accessible markers for improving the ALS diagnostic process by using ELISA in N = 70 ALS patients (N = 4 carrying TARDBP mutations), N = 40 age-comparable healthy controls (CTRL), N = 20 motor neuron disease mimics (MN-m), N = 20 Alzheimer’s disease (AD) and N = 15 frontotemporal lobar degeneration (FTLD) patients. Anti-TDP-43 NAb were found to be significantly increased in ALS patients compared to all the other groups (p < 0.001). On the other hand, the distribution of serum levels of TDP-43 protein was highly variable among the various groups. Levels were increased in ALS patients, albeit the highest values were detected in MN-m patients. NAb and protein serum levels failed to correlate. For the first time, we report that serum anti-TDP-43 NAb are detectable in human serum of both healthy controls and patients affected by a variety of neurodegenerative disorders; furthermore, their levels are increased in ALS patients, representing a potentially interesting trait core marker of this disease. Further studies are needed to clarify the exact role of the NAb. This information might be extremely useful for paving the way toward targeting TDP-43 by immunotherapy in ALS.