bluuebunny/crossref_metadata_2025_split huggingface dataset:
A common variant in 11q23.3 associated with hyperlipidemia is mediated by the binding and regulation of GATA4
Authors: Chou Wen-Cheng , Chen Wei-Ting , Shen Chen-Yang 
Published: January 2022

AbstractLarge-scale genome-wide associations comprising multiple studies have identified hundreds of genetic loci commonly associated with hyperlipidemia-related phenotypes. However, single large cohort remains necessary in aiming to investigate ethnicity-specific genetic risks and mechanical insights. A community-based cohort comprising 23,988 samples that included both genotype and biochemical information was assembled for the genome-wide association analysis (GWAS) of hyperlipidemia. The analysis identified fifty genetic variants (P < 5 × 10−8) on five different chromosomes, and a subsequent validation analysis confirmed the significance of the lead variants. Integrated analysis combined with cell-based experiments of the most statistically significant locus in 11q23.3 revealed rs651821 (P = 4.52 × 10−76) as the functional variant. We showed transcription factor GATA4 preferentially binds the T allele of rs651821, the protective allele for hyperlipidemia, which promoted APOA5 expression in liver cells and individuals with the TT genotype of rs651821. As GATA4-APOA5 axis maintains triglyceride homeostasis, GATA4 activation by phenylephrine implies synergism for lowering triglyceride levels in hyperlipidemia patients. Our study demonstrates that rs651821 mediates APOA5 activation via allele-specific regulation by GATA4. We suggest elevating GATA4 activity could provide a therapeutic potential for treating the development of hyperlipidemia.
Correlation-driven electron-hole asymmetry in graphene field effect devices
Authors: Dale Nicholas , Mori Ryo , Utama M. Iqbal Bakti , Denlinger Jonathan D. , Stansbury Conrad , Fatuzzo Claudia G. , Zhao Sihan , Lee Kyunghoon , Taniguchi Takashi , Watanabe Kenji , Jozwiak Chris , Bostwick Aaron , Rotenberg Eli , Koch Roland J. , Wang Feng , Lanzara Alessandra 
Published: January 2022

AbstractElectron-hole asymmetry is a fundamental property in solids that can determine the nature of quantum phase transitions and the regime of operation for devices. The observation of electron-hole asymmetry in graphene and recently in twisted graphene and moiré heterostructures has spurred interest into whether it stems from single-particle effects or from correlations, which are core to the emergence of intriguing phases in moiré systems. Here, we report an effective way to access electron-hole asymmetry in 2D materials by directly measuring the quasiparticle self-energy in graphene/Boron Nitride field-effect devices. As the chemical potential moves from the hole to the electron-doped side, we see an increased strength of electronic correlations manifested by an increase in the band velocity and inverse quasiparticle lifetime. These results suggest that electronic correlations intrinsically drive the electron-hole asymmetry in graphene and by leveraging this asymmetry can provide alternative avenues to generate exotic phases in twisted moiré heterostructures.
SUPT4H1-edited stem cell therapy rescues neuronal dysfunction in a mouse model for Huntington’s disease
Authors: Park Hyun Jung , Han Areum , Kim Ji Yeon , Choi Jiwoo , Bae Hee Sook , Cho Gyu-bon , Shin Hyejung , Shin Eun ji , Lee Kang-in , Kim Seokjoong , Lee Jae Young , Song Jihwan 
Published: January 2022

AbstractHuntington’s disease (HD) is a severe inherited neurological disorder caused by a CAG repeat expansion in the huntingtin gene (HTT), leading to the accumulation of mutant huntingtin with polyglutamine repeats. Despite its severity, there is no cure for this debilitating disease. HTT lowering strategies, including antisense oligonucleotides (ASO) showed promising results very recently. Attempts to develop stem cell-based therapeutics have shown efficacy in preclinical HD models. Using an HD patient’s autologous cells, which have genetic defects, may hamper therapeutic efficacy due to mutant HTT. Pretreating these cells to reduce mutant HTT expression and transcription may improve the transplanted cells’ therapeutic efficacy. To investigate this, we targeted the SUPT4H1 gene that selectively supports the transcription of long trinucleotide repeats. Transplanting SUPT4H1-edited HD-induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) into the YAC128 HD transgenic mouse model improved motor function compared to unedited HD iPSC-NPCs. Immunohistochemical analysis revealed reduced mutant HTT expression without compensating wild-type HTT expression. Further, SUPT4H1 editing increased neuronal and decreased reactive astrocyte differentiation in HD iPSC-NPCs compared to the unedited HD iPSC-NPCs. This suggests that ex vivo editing of SUPT4H1 can reduce mutant HTT expression and provide a therapeutic gene editing strategy for autologous stem cell transplantation in HD.
Diffusion kernel-based predictive modeling of KRAS dependency in KRAS wild type cancer cell lines
Authors: Ulmer Bastian , Odenthal Margarete , Buettner Reinhard , Roth Wilfried , Kloth Michael 
Published: January 2022

AbstractRecent progress in clinical development of KRAS inhibitors has raised interest in predicting the tumor dependency on frequently mutated RAS-pathway oncogenes. However, even without such activating mutations, RAS proteins represent core components in signal integration of several membrane-bound kinases. This raises the question of applications of specific inhibitors independent from the mutational status. Here, we examined CRISPR/RNAi data from over 700 cancer cell lines and identified a subset of cell lines without KRAS gain-of-function mutations (KRASwt) which are dependent on KRAS expression. Combining machine learning-based modeling and whole transcriptome data with prior variable selection through protein-protein interaction network analysis by a diffusion kernel successfully predicted KRAS dependency in the KRASwtsubgroup and in all investigated cancer cell lines. In contrast, modeling by RAS activating events (RAE) or previously published RAS RNA-signatures did not provide reliable results, highlighting the heterogeneous distribution of RAE in KRASwtcell lines and the importance of methodological references for expression signature modeling. Furthermore, we show that predictors of KRASwtmodels contain non-substitutable information signals, indicating a KRAS dependency phenotype in the KRASwtsubgroup. Our data suggest that KRAS dependent cancers harboring KRAS wild type status could be targeted by directed therapeutic approaches. RNA-based machine learning models could help in identifying responsive and non-responsive tumors.
Diagnostic error rates and associated factors for lower gastrointestinal perforation
Authors: Harada Taku , Watari Takashi , Watanuki Satoshi , Hiroshige Juichi , Kushiro Seiko , Miyagami Taiju , Syusa Syunsuke , Suzuki Satoshi , Hiyoshi Tetsuya , Hasegawa Suguru , Nabeshima Shigeki , Aihara Hidetoshi , Yamashita Shun , Tago Masaki , Yoshimura Fumitaka , Kunitomo Kotaro , Tsuji Takahiro , Hirose Masanori , Tsuchida Tomoya , Shimizu Taro 
Published: January 2022

AbstractLower gastrointestinal perforation is rare and challenging to diagnose in patients presenting with an acute abdomen. However, no study has examined the frequency and associated factors of diagnostic errors related to lower gastrointestinal perforation. This large-scale multicenter retrospective study investigated the frequency of diagnostic errors and identified the associated factors. Factors at the level of the patient, symptoms, situation, and physician were included in the analysis. Data were collected from nine institutions, between January 1, 2015 and December 31, 2019. Timely diagnosis was defined as diagnosis at the first visit in computed tomography (CT)-capable facilities or referral to an appropriate medical institution immediately following the first visit to a non-CT-capable facility. Cases not meeting this definition were defined as diagnostic errors that resulted in delayed diagnosis. Of the 439 cases of lower gastrointestinal perforation identified, delayed diagnosis occurred in 138 cases (31.4%). Multivariate logistic regression analysis revealed a significant association between examination by a non-generalist and delayed diagnosis. Other factors showing a tendency with delayed diagnosis included presence of fever, absence of abdominal tenderness, and unavailability of urgent radiology reports. Initial misdiagnoses were mainly gastroenteritis, constipation, and small bowel obstruction. In conclusion, diagnostic errors occurred in about one-third of patients with a lower gastrointestinal perforation.
Administration of mucuna beans (Mucuna pruriences (L.) DC. var. utilis) improves cognition and neuropathology of 3 × Tg-AD mice
Authors: Konishi Fumiko , Furusho Tadasu , Soeda Yoshiyuki , Yamauchi Jun , Kobayashi Shoko , Ito Masatoshi , Araki Takuma , Kogure Sarasa , Takashima Akihiko , Takekoshi Susumu 
Published: January 2022

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of extracellular amyloid-beta peptides (Aβ) resulting in senile plaques and intracellular hyperphosphorylated tau protein resulting in neurofibrillary tangles (NFTs). Mucuna beans (Mucuna pruriences (L.) DC. var. utilis) are unique plants containing 3–9% L-3,4-dihydroxyphenylalanine (L-DOPA). Here we investigated the effect of the administration of Mucuna beans on AD prevention by feeding triple-transgenic mice (3 × Tg-AD mice) with a diet containing Mucuna beans for 13 months. The levels of Aβ oligomers and detergent-insoluble phosphorylated tau decreased in the brain of mice fed with Mucuna beans (Mucuna group) compared to those of the Control group. Aβ accumulation and phosphorylated tau accumulation in the brain in the Mucuna group were also reduced. In addition, administration of Mucuna beans improved cognitive function. These results suggest that administration of Mucuna beans may have a preventive effect on AD development in 3 × Tg-AD mice.
Age-period-cohort analysis of the incidence of multiple sclerosis over twenty years in Lorraine, France
Authors: Gbaguidi Brigitte , Guillemin Francis , Soudant Marc , Debouverie Marc , Mathey Guillaume , Epstein Jonathan 
Published: January 2022

AbstractMultiple sclerosis (MS) is a neurodegenerative disease of the central nervous system. An increase in MS incidence over time is reported in several regions of the world. We aimed to describe the evolution of the annual MS incidence in the Lorraine region, France, from 1996 to 2015 and to analyze potential components of a possible change by a temporal effect of age at MS onset, MS onset period, and birth cohort, overall and for each sex. Cases were identified from ReLSEP, a population-based registry of MS cases living in Lorraine, northeastern France, with MS onset between 1996 and 2015. Age-period-cohort modeling was used to describe trends in MS incidence. Annual age- and sex-standardized incidences were relatively stable: 6.76/100 000 population (95%CI [5.76–7.91]) in 1996 and 6.78/100 000 (95%CI [5.72–7.97]) in 2015. The incidence ratio between women and men was 2.4. For all time periods, the peak incidence occurred between ages 25 and 35 years. Age-period–adjusted cohort and age-cohort–adjusted period analyses did not reveal a period or cohort effect. The incidence of MS remained stable over the study period in Lorraine, and we could not identify any particular effect of disease onset period or birth period on this evolution.
Physically unclonable functions taggant for universal steganographic prints
Authors: Fukuoka Takao , Mori Yasushige , Yasunaga Toshiya , Namura Kyoko , Suzuki Motofumi , Yamaguchi Akinobu 
Published: January 2022

AbstractCounterfeiting of financial cards and marketable securities is a major social problem globally. Electronic identification and image recognition are common anti-counterfeiting techniques, yet they can be overcome by understanding the corresponding algorithms and analysis methods. The present work describes a physically unclonable functions taggant, in an aqueous-soluble ink, based on surface-enhanced Raman scattering of discrete self-assemblies of Au nanoparticles. Using this stealth nanobeacon, we detected a fingerprint-type Raman spectroscopy signal that we clearly identified even on a business card with a pigment mask such as copper-phthalocyanine printed on it. Accordingly, we have overcome the reverse engineering problem that is otherwise inherent to analogous anti-counterfeiting techniques. One can readily tailor the ink to various information needs and application requirements. Our stealth nanobeacon printing will be particularly useful for steganography and provide a sensitive fingerprint for anti-counterfeiting.
Exploiting time series of Sentinel-1 and Sentinel-2 to detect grassland mowing events using deep learning with reject region
Authors: Komisarenko Viacheslav , Voormansik Kaupo , Elshawi Radwa , Sakr Sherif 
Published: January 2022

AbstractGovernments pay agencies to control the activities of farmers who receive governmental support. Field visits are costly and highly time-consuming; hence remote sensing is widely used for monitoring farmers’ activities. Nowadays, a vast amount of available data from the Sentinel mission significantly boosted research in agriculture. Estonia is among the first countries to take advantage of this data source to automate mowing and ploughing events detection across the country. Although techniques that rely on optical data for monitoring agriculture events are favourable, the availability of such data during the growing season is limited. Thus, alternative data sources have to be evaluated. In this paper, we developed a deep learning model with an integrated reject option for detecting grassland mowing events using time series of Sentinel-1 and Sentinel-2 optical images acquired from 2000 fields in Estonia in 2018 during the vegetative season. The rejection mechanism is based on a threshold over the prediction confidence of the proposed model. The proposed model significantly outperforms the state-of-the-art technique and achieves event accuracy of 73.3% and end of season accuracy of 94.8%.
Diagnosis of early mild cognitive impairment using a multiobjective optimization algorithm based on T1-MRI data
Authors: Zamani Jafar , Sadr Ali , Javadi Amir-Homayoun 
Published: January 2022

AbstractAlzheimer’s disease (AD) is the most prevalent form of dementia. The accurate diagnosis of AD, especially in the early phases is very important for timely intervention. It has been suggested that brain atrophy, as measured with structural magnetic resonance imaging (sMRI), can be an efficacy marker of neurodegeneration. While classification methods have been successful in diagnosis of AD, the performance of such methods have been very poor in diagnosis of those in early stages of mild cognitive impairment (EMCI). Therefore, in this study we investigated whether optimisation based on evolutionary algorithms (EA) can be an effective tool in diagnosis of EMCI as compared to cognitively normal participants (CNs). Structural MRI data for patients with EMCI (n = 54) and CN participants (n = 56) was extracted from Alzheimer’s disease Neuroimaging Initiative (ADNI). Using three automatic brain segmentation methods, we extracted volumetric parameters as input to the optimisation algorithms. Our method achieved classification accuracy of greater than 93%. This accuracy level is higher than the previously suggested methods of classification of CN and EMCI using a single- or multiple modalities of imaging data. Our results show that with an effective optimisation method, a single modality of biomarkers can be enough to achieve a high classification accuracy.
A panel of emerging EMT genes identified in malignant mesothelioma
Authors: Wu Licun , Amjad Shaheer , Yun Hana , Mani Sendurai , de Perrot Marc 
Published: January 2022

AbstractMalignant mesothelioma (MESO) is a highly aggressive cancer with poor prognosis. Epithelial–mesenchymal transition (EMT) is a critical process in malignancies involved in tumor angiogenesis, progression, invasion and metastasis, immunosuppressive microenvironment and therapy resistance. However, there is a lack of specific biomarkers to identify EMT in MESO. Biphasic MESO with dual phenotypes could be an optimal model to study EMT process. Using a powerful EMTome to investigate EMT gene signature, we identified a panel of EMT genes COL5A2, ITGAV, SPARC and ACTA2 in MESO. In combination with TCGA database, Timer2.0 and other resources, we observed that overexpression of these emerging genes is positively correlated with immunosuppressive infiltration, and an unfavorable factor to patient survival in MESO. The expression of these genes was confirmed in our patients and human cell lines. Our findings suggest that these genes may be novel targets for therapeutics and prognosis in MESO and other types of cancers.
Evolution of the bovid cranium: morphological diversification under allometric constraint
Authors: Bibi Faysal , Tyler Joshua 
Published: January 2022

AbstractThe role of environmental selection in generating novel morphology is often taken for granted, and morphology is generally assumed to be adaptive. Bovids (antelopes and relatives) are widely differentiated in their dietary and climatic preferences, and presumably their cranial morphologies are the result of adaptation to different environmental pressures. In order to test these ideas, we performed 3D geometric morphometric analyses on 141 crania representing 96 bovid species in order to assess the influence of both extrinsic (e.g. diet, habitat) and intrinsic (size, modularity) factors on cranial shape. Surprisingly, we find that bovid crania are highly clumped in morphospace, with a large number of ecologically disparate species occupying a very similar range of morphology clustered around the mean shape. Differences in shape among dietary, habitat, and net primary productivity categories are largely non-significant, but we found a strong interaction between size and diet in explaining shape. We furthermore found no evidence for modularity having played a role in the generation of cranial differences across the bovid tree. Rather, the distribution of bovid cranial morphospace appears to be mainly the result of constraints imposed by a deeply conserved size-shape allometry, and dietary diversification the result of adaptation of existing allometric pathways.
Evolutionary alterations in gene expression and enzymatic activities of gibberellin 3-oxidase 1 in Oryza
Authors: Kawai Kyosuke , Takehara Sayaka , Kashio Toru , Morii Minami , Sugihara Akihiko , Yoshimura Hisako , Ito Aya , Hattori Masako , Toda Yosuke , Kojima Mikiko , Takebayashi Yumiko , Furuumi Hiroyasu , Nonomura Ken-ichi , Mikami Bunzo , Akagi Takashi , Sakakibara Hitoshi , Kitano Hidemi , Matsuoka Makoto , Ueguchi-Tanaka Miyako 
Published: January 2022

AbstractProper anther and pollen development are important for plant reproduction. The plant hormone gibberellin is important for anther development in rice, but its gametophytic functions remain largely unknown. Here, we report the functional and evolutionary analyses of rice gibberellin 3-oxidase 1 (OsGA3ox1), a gibberellin synthetic enzyme specifically expressed in the late developmental stages of anthers. Enzymatic and X-ray crystallography analyses reveal that OsGA3ox1 has a higher GA7 synthesis ratio than OsGA3ox2. In addition, we generate an osga3ox1 knockout mutant by genome editing and demonstrate the bioactive gibberellic acid synthesis by the OsGA3ox1 action during starch accumulation in pollen via invertase regulation. Furthermore, we analyze the evolution of Oryza GA3ox1s and reveal that their enzyme activity and gene expression have evolved in a way that is characteristic of the Oryza genus and contribute to their male reproduction ability.
Competition and resource depletion shape the thermal response of population fitness in Aedes aegypti
Authors: Huxley Paul J. , Murray Kris A. , Pawar Samraat , Cator Lauren J. 
Published: January 2022

AbstractMathematical models that incorporate the temperature dependence of lab-measured life history traits are increasingly being used to predict how climatic warming will affect ectotherms, including disease vectors and other arthropods. These temperature-trait relationships are typically measured under laboratory conditions that ignore how conspecific competition in depleting resource environments—a commonly occurring scenario in nature—regulates natural populations. Here, we used laboratory experiments on the mosquito Aedes aegypti, combined with a stage-structured population model, to investigate this issue. We find that intensified larval competition in ecologically-realistic depleting resource environments can significantly diminish the vector’s maximal population-level fitness across the entire temperature range, cause a ~6 °C decrease in the optimal temperature for fitness, and contract its thermal niche width by ~10 °C. Our results provide evidence for the importance of considering intra-specific competition under depleting resources when predicting how arthropod populations will respond to climatic warming.
Linker micro-regulation of a Hofmann-based metal–organic framework for efficient propylene/propane separation
Authors: Liu Puxu , Chen Kaiming , Chen Yang , Wang Xiaoqing , Yang Jiangfeng , Li Libo , Li Jinping 
Published: January 2022

A highly stable Hofmann-based metal−organic framework has been purposely synthesized for efficient C3H6/C3H8 separation through the linker modification strategy using direct mixing method under ambient conditions.
Exploiting angular spread in channel estimation of millimeter wave MIMO system
Authors: You You , Zhang Li 
Published: January 2022

AbstractMillimeter wave (mmWave) frequency spectrum can mitigate severe spectrum shortage caused by the explosive growth of mobile data demand. To overcome the high propagation loss of mmWave signals, massive multi‐input multi‐output (MIMO) and hybrid architecture are employed. As in microwave communication systems, channel state information (CSI) is essential to fully achieve the advantages of mmWave communication. However, due to the massive number of antennas and hybrid architecture, the CSI acquisition is challenging. The sparsity of mmWave channel can be utilized to reduce the training overhead. In addition to sparsity, real‐world measurements in dense urban propagation environments reveal that the mmWave channel may spread in form of cluster of paths over the angular domains, namely the angular spread. In this paper, it is utilized to formulate the channel estimation as a block‐sparse signal recovery problem. The block orthogonal matching pursuit (BOMP) is used to validate the model. Then, block fast Bayesian matching pursuit (BFBMP) algorithm is proposed to solve the above problem. Compared with other existing channel estimation methods, simulation results show that the angular spread feature and the proposed BFBMP can considerably improve the CSI estimation with less complexity.