bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Cathepsin D in the central nervous system results in microglia and astrocyte activation and the accumulation of proteinopathy-related proteins
Authors: Suzuki Chigure , Yamaguchi Junji , Sanada Takahito , Oliva Trejo Juan Alejandro , Kakuta Souichirou , Shibata Masahiro , Tanida Isei , Uchiyama Yasuo 
Published: July 2022

AbstractNeuronal ceroid lipofuscinosis is one of many neurodegenerative storage diseases characterized by excessive accumulation of lipofuscins. CLN10 disease, an early infantile neuronal ceroid lipofuscinosis, is associated with a gene that encodes cathepsin D (CtsD), one of the major lysosomal proteases. Whole body CtsD-knockout mice show neurodegenerative phenotypes with the accumulation of lipofuscins in the brain and also show defects in other tissues including intestinal necrosis. To clarify the precise role of CtsD in the central nervous system (CNS), we generated a CNS-specific CtsD-knockout mouse (CtsD-CKO). CtsD-CKO mice were born normally but developed seizures and their growth stunted at around postnatal day 23 ± 1. CtsD-CKO did not exhibit apparent intestinal symptoms as those observed in whole body knockout. Histologically, autofluorescent materials were detected in several areas of the CtsD-CKO mouse’s brain, including: thalamus, cerebral cortex, hippocampus, and cerebellum. Expression of ubiquitin and autophagy-associated proteins was also increased, suggesting that the autophagy-lysosome system was impaired. Microglia and astrocytes were activated in the CtsD-CKO thalamus, and inducible nitric oxide synthase (iNOS), an inflammation marker, was increased in the microglia. Interestingly, deposits of proteinopathy-related proteins, phosphorylated α-synuclein, and Tau protein were also increased in the thalamus of CtsD-CKO infant mice. Considering these results, we propose thatt the CtsD-CKO mouse is a useful mouse model to investigate the contribution of cathepsin D to the early phases of neurodegenerative diseases in relation to lipofuscins, proteinopathy-related proteins and activation of microglia and astrocytes.
A dynamically structured matrix population model for insect life histories observed under variable environmental conditions
Authors: Erguler Kamil , Mendel Jacob , Petrić Dušan Veljko , Petrić Mina , Kavran Mihaela , Demirok Murat Can , Gunay Filiz , Georgiades Pantelis , Alten Bulent , Lelieveld Jos 
Published: July 2022

AbstractVarious environmental drivers influence life processes of insect vectors that transmit human disease. Life histories observed under experimental conditions can reveal such complex links; however, designing informative experiments for insects is challenging. Furthermore, inferences obtained under controlled conditions often extrapolate poorly to field conditions. Here, we introduce a pseudo-stage-structured population dynamics model to describe insect development as a renewal process with variable rates. The model permits representing realistic life stage durations under constant and variable environmental conditions. Using the model, we demonstrate how random environmental variations result in fluctuating development rates and affect stage duration. We apply the model to infer environmental dependencies from the life history observations of two common disease vectors, the southern (Culex quinquefasciatus) and northern (Culex pipiens) house mosquito. We identify photoperiod, in addition to temperature, as pivotal in regulating larva stage duration, and find that carefully timed life history observations under semi-field conditions accurately predict insect development throughout the year. The approach we describe augments existing methods of life table design and analysis, and contributes to the development of large-scale climate- and environment-driven population dynamics models for important disease vectors.
Interval-valued intuitionistic fuzzy multi-attribute group decision-making method considering risk preference of decision-makers and its application
Authors: Fu Sha , Xiao Ye-zhi , Zhou Hang-jun 
Published: July 2022

AbstractAn improved interval-valued intuitionistic fuzzy multi-attribute group decision-making method considering the risk preference of decision-makers is proposed to solve the multi-attribute group decision-making problem with interval-valued intuitionistic fuzzy numbers and the condition that the attribute weight information is completely unknown. Firstly, the decision-maker weight of each attribute is determined by combining similarity and proximity. In order to consider the influence of the decision-maker's risk preference on the decision result and avoid the asymptotic behavior of interval-valued intuitionistic fuzzy matrix, the risk aversion coefficient of the decision-maker is introduced and combined with the determined decision-maker's weight aggregation to form a group decision matrix. Then, the information of group decision matrix is mined, and the interval-valued intuitionistic fuzzy entropy is used to determine the attribute weight and relative weight. Based on the interval-valued intuitionistic fuzzy distance measure formula and the TODIM method, the overall superiority of each scheme relative to other schemes is obtained by calculating the superiority between schemes, and the optimal scheme is determined by comparing and sequencing. Finally, the rationality and effectiveness of the proposed method are verified by an example of mechanical assembly supplier selection decision.
Deep convolutional neural network-based skeletal classification of cephalometric image compared with automated-tracing software
Authors: Kim Ho-Jin , Kim Kyoung Dong , Kim Do-Hoon 
Published: July 2022

AbstractThis study aimed to investigate deep convolutional neural network- (DCNN-) based artificial intelligence (AI) model using cephalometric images for the classification of sagittal skeletal relationships and compare the performance of the newly developed DCNN-based AI model with that of the automated-tracing AI software. A total of 1574 cephalometric images were included and classified based on the A-point-Nasion- (N-) point-B-point (ANB) angle (Class I being 0–4°, Class II > 4°, and Class III < 0°). The DCNN-based AI model was developed using training (1334 images) and validation (120 images) sets with a standard classification label for the individual images. A test set of 120 images was used to compare the AI models. The agreement of the DCNN-based AI model or the automated-tracing AI software with a standard classification label was measured using Cohen’s kappa coefficient (0.913 for the DCNN-based AI model; 0.775 for the automated-tracing AI software). In terms of their performances, the micro-average values of the DCNN-based AI model (sensitivity, 0.94; specificity, 0.97; precision, 0.94; accuracy, 0.96) were higher than those of the automated-tracing AI software (sensitivity, 0.85; specificity, 0.93; precision, 0.85; accuracy, 0.90). With regard to the sagittal skeletal classification using cephalometric images, the DCNN-based AI model outperformed the automated-tracing AI software.
Bound states in the continuum (BIC) protected by self-sustained potential barriers in a flat band system
Authors: Zhang Yi-Cai 
Published: July 2022

AbstractIn this work, we investigate the bound states in the continuum (BIC) of a one-dimensional spin-1 flat band system. It is found that, when the potential is sufficiently strong, there exists an effective attractive potential well surrounded by infinitely high self-sustained barriers. Consequently, there exist some BIC in the effective potential well. These bound states are protected by the infinitely high potential barriers, which could not decay into the continuum. Taking a long-ranged Coulomb potential and a short-ranged exponential potential as two examples, the bound state energies are obtained. For a Coulomb potential, there exists a series of critical potential strengths, near which the bound state energy can go to infinity. For a sufficiently strong exponential potential, there exist two different bound states with a same number of wave function nodes. The existence of BIC protected by the self-sustained potential barriers is quite a universal phenomenon in the flat band system under a strong potential. A necessary condition for the existence of BIC is that the maximum of potential is larger than two times band gap.
Improved geometric accuracy of whole body diffusion-weighted imaging at 1.5T and 3T using reverse polarity gradients
Authors: Sjöholm T. , Kullberg J. , Strand R. , Engström M. , Ahlström H. , Malmberg F. 
Published: July 2022

AbstractWhole body diffusion-weighted imaging (WB-DWI) is increasingly used in oncological applications, but suffers from misalignments due to susceptibility-induced geometric distortion. As such, DWI and structural images acquired in the same scan session are not geometrically aligned, leading to difficulties in e.g. lesion detection and segmentation. In this work we assess the performance of the reverse polarity gradient (RPG) method for correction of WB-DWI geometric distortion. Multi-station DWI and structural magnetic resonance imaging (MRI) data of healthy controls were acquired at 1.5T (n = 20) and 3T (n = 20). DWI data was distortion corrected using the RPG method based on b = 0 s/mm2 (b0) and b = 50 s/mm2 (b50) DWI acquisitions. Mutual information (MI) between low b-value DWI and structural data increased with distortion correction (P < 0.05), while improvements in region of interest (ROI) based similarity metrics, comparing the position of incidental findings on DWI and structural data, were location dependent. Small numerical differences between non-corrected and distortion corrected apparent diffusion coefficient (ADC) values were measured. Visually, the distortion correction improved spine alignment at station borders, but introduced registration-based artefacts mainly for the spleen and kidneys. Overall, the RPG distortion correction gave an improved geometric accuracy for WB-DWI data acquired at 1.5T and 3T. The b0- and b50-based distortion corrections had a very similar performance.
Intramuscular delivery of formulated RNA encoding six linked nanobodies is highly protective for exposures to three Botulinum neurotoxin serotypes
Authors: Mukherjee Jean , Ondeck Celinia A. , Tremblay Jacqueline M. , Archer Jacob , Debatis Michelle , Foss Alexa , Awata Junya , Erasmus Jesse H. , McNutt Patrick M. , Shoemaker Charles B. 
Published: July 2022

AbstractSingle domain antibodies (sdAbs), also called nanobodies, have substantial biophysical advantages over conventional antibodies and are increasingly being employed as components of immunotherapeutic agents. One particularly favorable property is the ability to link different sdAbs into heteromultimers. This feature allows production of single molecules capable of simultaneously targeting more than one antigen. In addition, cooperative binding of multiple linked sdAbs to non-overlapping epitopes on the same target can produce synergistic improvements in target affinity, variant specificity, and in vivo potencies. Here we seek to test the option of increased component sdAbs in these heteromultimers by testing different sdAb heterohexamers in which each of the six camelid sdAb components (VHHs) can neutralize one of three different Botulinum neurotoxin (BoNT) serotypes, A, B or E. Each heterohexamer bound all three targeted BoNT serotypes and protected mice from at least 100 MIPLD50 of each serotype. To test the potential of mRNA therapeutics encoding long sdAb heteromultimers, one heterohexamer was encoded as replicating RNA (repRNA), formulated with a cationic nanocarrier, and delivered to mice via intramuscular injection. Heterohexamer antitoxin serum expression levels were easily detected by 8 h post-treatment, peaked at 5–10 nM around two days, and persisted for more than three days. Mice treated with the formulated repRNA one day post-treatment survived challenge with 100 MIPLD50 of each toxin serotype, demonstrating the function of all six component VHHs. Use of long sdAb multimers, administered as proteins or repRNA, offer the potential for substantially improved versatility in the development of antibody-based therapeutics.
Evaluation of long-term outcomes associated with extended heavy-silicone oil use for the treatment of inferior retinal detachment
Authors: Horozoglu Fatih , Sener Hidayet , Polat Osman Ahmet , Sever Ozkan , Potoglu Busra , Celik Erkan , Turkoglu Elif Betul , Evereklioglu Cem 
Published: July 2022

AbstractTo evaluate macular status with optical coherence tomography (OCT) in eyes that underwent pars plana vitrectomy (PPV) and heavy-silicone oil (HSO) endotamponade for the treatment of rhegmatogenous retinal detachment (RRD) with inferior breaks. Twenty eyes of 20 patients who have RRD with inferior breaks included in the study. Oxane HD was used as an intraocular tamponade for all surgeries. Postoperatively, anatomic reattachment, macular status using OCT imaging, and any long-term complications were evaluated. The mean age was 60.4 ± 11.2 years (range, 37–83). The duration of HSO endotamponade was 15.3 ± 11.0 months (range, 6–48) with some postoperative complications such as HSO emulsification, intraocular pressure elevation, and epiretinal membrane (ERM) formation. Mean follow-up time was 19.5 ± 10.5 months (range, 10–59) after HSO removal or ERM surgery. Primary reattachment was achieved in 90% of eyes and the success rate was 100% with further interventions. Ellipsoid zone (EZ) was continuous in 13 of 20 eyes in which OCT imaging performed as well as the fellow eye. PPV and heavy-silicone oil injection for the treatment of eyes with RRD from inferior break(s) have a good long-term EZ continuity. ERM formation and its removal do not affect EZ.
Tetradentate copper complex supported on boehmite nanoparticles as an efficient and heterogeneous reusable nanocatalyst for the synthesis of diaryl ethers
Authors: Jabbari Arida , Moradi Parisa , Hajjami Maryam , Tahmasbi Bahman 
Published: July 2022

AbstractIn this work boehmite nanoparticles (BNPs) were prepared through addition of aqueous solution of NaOH to solution of Al(NO3)3·9H2O. Then, the surface of BNPs was modified by (3-chloropropyl)trimethoxysilane (CPTMS) and further tetradentate ligand (MP-bis(AMP)) was anchored on its surface. At final step, a tetradentate organometallic complex of copper was stabilized on the surface of modified BNPs (Cu(II)-MP-bis(AMP)@boehmite). These obtained nanoparticles were characterized using SEM imaging, WDX, EDS, AAS and TGA analysis, BET method, FT-IR spectroscopy, and XRD pattern. In continue, the catalytic activity of Cu(II)-MP-bis(AMP)@boehmite has been used as a much efficient, reusable and hybrid of organic–inorganic nanocatalyst in the synthesis of ether derivatives through C–O coupling reaction under palladium-free and phosphine-free conditions. Cu(II)-MP-bis(AMP)@boehmite catalyst has been recovered and reused again for several times in the synthesis of ether derivatives.
A medium-chain triglyceride containing ketogenic diet exacerbates cardiomyopathy in a CRISPR/Cas9 gene-edited rat model with Duchenne muscular dystrophy
Authors: Fujikura Yuri , Kimura Koichi , Yamanouchi Keitaro , Sugihara Hidetoshi , Hatakeyama Masaki , Zhuang Haotong , Abe Tomoki , Daimon Masao , Morita Hiroyuki , Komuro Issei , Oishi Katsutaka 
Published: July 2022

AbstractDuchenne muscular dystrophy (DMD) is an X-linked recessive myopathy caused by dystrophin mutations. Although respiratory management has improved the prognosis of patients with DMD, inevitable progressive cardiomyopathy is a current leading cause of premature death. Recently, we showed that a medium-chain triglyceride containing ketogenic diet (MCTKD) improves skeletal muscle function and pathology in a CRISPR/Cas9 gene-edited rat model with DMD. In this study, we sought to clarify whether MCTKD also improves the cardiomyopathy in these rats. DMD rats were fed either the MCTKD or normal diet (ND) from ages of 3 weeks to 9 months old. Compared with the ND-fed rats, MCTKD-fed rats showed significantly prolonged QRS duration, decreased left ventricular fractional shortening, an increased heart weight/body weight ratio, and progression of cardiac fibrosis. In contrast to our previous study which found that MCTKD improved skeletal myopathy, the current study showed unexpected exacerbation of the cardiomyopathy. Further studies are needed to explore the underlying mechanisms for these differences and to explore modified dietary options that improve skeletal and cardiac muscles simultaneously.
The effects of protected areas on the ecological niches of birds and mammals
Authors: Santangeli Andrea , Mammola Stefano , Lehikoinen Aleksi , Rajasärkkä Ari , Lindén Andreas , Saastamoinen Marjo 
Published: July 2022

AbstractProtected areas are a cornerstone for biodiversity conservation, and typically support more natural and undisturbed habitats compared to unprotected lands. The effect of protected areas on intra-specific ecological niche has been rarely investigated. Here, we explore potential differences in ecological niche properties of birds and mammals across protected and unprotected areas, and relate such differences to species traits. We combine two decades of survey data of birds and mammals from protected and unprotected areas, and apply robust matching to obtain a set of environmentally comparable protected and unprotected sites. Next, we calculate intra-specific niche volume change and habitat shift between protected and unprotected areas, and use generalized linear mixed models to explain these responses with species traits (habitat specialization, body mass, diet, and red list status). The majority of bird and mammal species (83% and 90%, respectively) show different habitat use when occurring within and outside protected areas, with the magnitude of this shift highly varying across species. A minority of species (16% of birds and 10% of mammals) do not change their niche volume nor shift their habitat between protected and unprotected areas. Variation in niche properties is largely unrelated to species traits. Overall, the varying ecological niche responses of birds and mammals to protected areas underscore that there is no universal niche-based response, and that niche responses to land protection are species-specific.
Capacitive humidity sensing properties of freestanding bendable porous SiO2/Si thin films
Authors: Park Soobin , Seo Jinmyeong , Park Jungjoon , Hwang Inseong , Lee Han-Seung , Jung Hyunsung , Yoo Bongyoung 
Published: July 2022

AbstractThe fabrication of freestanding bendable films without polymer substrates is demonstrated as a capacitive humidity-sensing material. The bendable and porous SiO2/Si films are simply prepared by electrochemical-assisted stripping, metal-assisted chemical etching, followed by oxidation procedures. The capacitive humidity-sensing properties of the fabricated porous SiO2/Si film are characterized as a function of the relative humidity and frequency. The remarkable sensing performance is demonstrated in the wide RH range from 13.8 to 79.0%. The sensing behavior of the porous SiO2/Si film is studied by electrochemical impedance spectroscopy analysis. Additionally, the reliability of the porous SiO2/Si sensing material is confirmed by cyclic and long-term sensing tests.
Fast cross-staining alignment of gigapixel whole slide images with application to prostate cancer and breast cancer analysis
Authors: Wang Ching-Wei , Lee Yu-Ching , Khalil Muhammad-Adil , Lin Kuan-Yu , Yu Cheng-Ping , Lien Huang-Chun 
Published: July 2022

AbstractJoint analysis of multiple protein expressions and tissue morphology patterns is important for disease diagnosis, treatment planning, and drug development, requiring cross-staining alignment of multiple immunohistochemical and histopathological slides. However, cross-staining alignment of enormous gigapixel whole slide images (WSIs) at single cell precision is difficult. Apart from gigantic data dimensions of WSIs, there are large variations on the cell appearance and tissue morphology across different staining together with morphological deformations caused by slide preparation. The goal of this study is to build an image registration framework for cross-staining alignment of gigapixel WSIs of histopathological and immunohistochemical microscopic slides and assess its clinical applicability. To the authors’ best knowledge, this is the first study to perform real time fully automatic cross staining alignment of WSIs with 40× and 20× objective magnification. The proposed WSI registration framework consists of a rapid global image registration module, a real time interactive field of view (FOV) localization model and a real time propagated multi-level image registration module. In this study, the proposed method is evaluated on two kinds of cancer datasets from two hospitals using different digital scanners, including a dual staining breast cancer data set with 43 hematoxylin and eosin (H&E) WSIs and 43 immunohistochemical (IHC) CK(AE1/AE3) WSIs, and a triple staining prostate cancer data set containing 30 H&E WSIs, 30 IHC CK18 WSIs, and 30 IHC HMCK WSIs. In evaluation, the registration performance is measured by not only registration accuracy but also computational time. The results show that the proposed method achieves high accuracy of 0.833 ± 0.0674 for the triple-staining prostate cancer data set and 0.931 ± 0.0455 for the dual-staining breast cancer data set, respectively, and takes only 4.34 s per WSI registration on average. In addition, for 30.23% data, the proposed method takes less than 1 s for WSI registration. In comparison with the benchmark methods, the proposed method demonstrates superior performance in registration accuracy and computational time, which has great potentials for assisting medical doctors to identify cancerous tissues and determine the cancer stage in clinical practice.
Rapid reverse genetics systems for Nothobranchius furzeri, a suitable model organism to study vertebrate aging
Authors: Oginuma Masayuki , Nishida Moana , Ohmura-Adachi Tomomi , Abe Kota , Ogamino Shohei , Mogi Chihiro , Matsui Hideaki , Ishitani Tohru 
Published: July 2022

AbstractThe African turquoise killifish Nothobranchius furzeri (N. furzeri) is a useful model organism for studying aging, age-related diseases, and embryonic diapause. CRISPR/Cas9-mediated gene knockout and Tol2 transposon-mediated transgenesis in N. furzeri have been reported previously. However, these methods take time to generate knockout and transgenic fish. In addition, knock-in technology that inserts large DNA fragments as fluorescent reporter constructs into the target gene in N. furzeri has not yet been established. Here, we show that triple-target CRISPR-mediated single gene disruption efficiently produces whole-body biallelic knockout and enables the examination of gene function in the F0 generation. In addition, we developed a method for creating the knock-in reporter N. furzeri without crossing by optimizing the CRISPR/Cas9 system. These methods drastically reduce the duration of experiments, and we think that these advances will accelerate aging and developmental studies using N. furzeri.