bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryo model completes gastrulation to neurulation and organogenesis
Authors: Amadei Gianluca , Handford Charlotte E. , Qiu Chengxiang , De Jonghe Joachim , Greenfeld Hannah , Tran Martin , Martin Beth K. , Chen Dong-Yuan , Aguilera-Castrejon Alejandro , Hanna Jacob H. , Elowitz Michael B. , Hollfelder Florian , Shendure Jay , Glover David M. , Zernicka-Goetz Magdalena 
Published: August 2022

AbstractEmbryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro1–5, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells6–11. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization. Our embryo model displays headfolds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extraembryonic yolk sac that initiates blood island development. Notably, we demonstrate that the neurulating embryo model assembled from Pax6-knockout ES cells aggregated with wild-type TS cells and iXEN cells recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6-knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse cell lineages and genes in development. Our results demonstrate the self-organization ability of ES cells and two types of extraembryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.
Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial
Authors: Gogishvili Miranda , Melkadze Tamar , Makharadze Tamta , Giorgadze Davit , Dvorkin Mikhail , Penkov Konstantin , Laktionov Konstantin , Nemsadze Gia , Nechaeva Marina , Rozhkova Irina , Kalinka Ewa , Gessner Christian , Moreno-Jaime Brizio , Passalacqua Rodolfo , Li Siyu , McGuire Kristina , Kaul Manika , Paccaly Anne , Quek Ruben G. W. , Gao Bo , Seebach Frank , Weinreich David M. , Yancopoulos George D. , Lowy Israel , Gullo Giuseppe , Rietschel Petra 
Published: August 2022

AbstractFirst-line cemiplimab (anti-programmed cell death-1 (PD-1)) monotherapy has previously shown significant improvement in overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced non-small cell lung cancer (aNSCLC) and PD-ligand 1 (PD-L1) expression ≥50%. EMPOWER-Lung 3 (NCT03409614), a double-blind, placebo-controlled, phase 3 study, examined cemiplimab plus platinum-doublet chemotherapy as first-line treatment for aNSCLC, irrespective of PD-L1 expression or histology. In this study, 466 patients with stage III/IV aNSCLC without EGFR, ALK or ROS1 genomic tumor aberrations were randomized (2:1) to receive cemiplimab 350 mg (n = 312) or placebo (n = 154) every 3 weeks for up to 108 weeks in combination with four cycles of platinum-doublet chemotherapy (followed by pemetrexed maintenance as indicated). In total, 57.1% (266/466 patients) had non-squamous NSCLC, and 85.2% (397/466 patients) had stage IV disease. The primary endpoint was OS. The trial was stopped early per recommendation of the independent data monitoring committee, based on meeting preset OS efficacy criteria: median OS was 21.9 months (95% confidence interval (CI), 15.5–not evaluable) with cemiplimab plus chemotherapy versus 13.0 months (95% CI, 11.9–16.1) with placebo plus chemotherapy (hazard ratio (HR) = 0.71; 95% CI, 0.53–0.93; P = 0.014). Grade ≥3 adverse events occurred with cemiplimab plus chemotherapy (43.6%, 136/312 patients) and placebo plus chemotherapy (31.4%, 48/153 patients). Cemiplimab is only the second anti-PD-1/PD-L1 agent to show efficacy in aNSCLC as both monotherapy and in combination with chemotherapy for both squamous and non-squamous histologies.
Extended longevity of DNA preservation in Levantine Paleolithic sediments, Sefunim Cave, Israel
Authors: Slon Viviane , Clark Jamie L. , Friesem David E. , Orbach Meir , Porat Naomi , Meyer Matthias , Kandel Andrew W. , Shimelmitz Ron 
Published: August 2022

AbstractPaleogenomic research can elucidate the evolutionary history of human and faunal populations. Although the Levant is a key land-bridge between Africa and Eurasia, thus far, relatively little ancient DNA data has been generated from this region, since DNA degrades faster in warm climates. As sediments can be a source of ancient DNA, we analyzed 33 sediment samples from different sedimentological contexts in the Paleolithic layers of Sefunim Cave (Israel). Four contained traces of ancient Cervidae and Hyaenidae mitochondrial DNA. Dating by optical luminescence and radiocarbon indicates that the DNA comes from layers between 30,000 and 70,000 years old, surpassing theoretical expectations regarding the longevity of DNA deposited in such a warm environment. Both identified taxa are present in the zooarchaeological record of the site but have since gone extinct from the region, and a geoarchaeological study suggests little movement of the sediments after their deposition, lending further support to our findings. We provide details on the local conditions in the cave, which we hypothesize were particularly conducive to the long-term preservation of DNA—information that will be pertinent for future endeavors aimed at recovering ancient DNA from the Levant and other similarly challenging contexts.
Emergence of sensory attenuation based upon the free-energy principle
Authors: Idei Hayato , Ohata Wataru , Yamashita Yuichi , Ogata Tetsuya , Tani Jun 
Published: August 2022

AbstractThe brain attenuates its responses to self-produced exteroceptions (e.g., we cannot tickle ourselves). Is this phenomenon, known as sensory attenuation, enabled innately, or acquired through learning? Here, our simulation study using a multimodal hierarchical recurrent neural network model, based on variational free-energy minimization, shows that a mechanism for sensory attenuation can develop through learning of two distinct types of sensorimotor experience, involving self-produced or externally produced exteroceptions. For each sensorimotor context, a particular free-energy state emerged through interaction between top-down prediction with precision and bottom-up sensory prediction error from each sensory area. The executive area in the network served as an information hub. Consequently, shifts between the two sensorimotor contexts triggered transitions from one free-energy state to another in the network via executive control, which caused shifts between attenuating and amplifying prediction-error-induced responses in the sensory areas. This study situates emergence of sensory attenuation (or self-other distinction) in development of distinct free-energy states in the dynamic hierarchical neural system.
Electrical resistivity of polycrystalline graphene: effect of grain-boundary-induced strain fields
Authors: Krasavin S. E. , Osipov V. A. 
Published: August 2022

AbstractWe have revealed the decisive role of grain-boundary-induced strain fields in electron scattering in polycrystalline graphene. To this end, we have formulated the model based on Boltzmann transport theory which properly takes into account the microscopic structure of grain boundaries (GB) as a repeated sequence of heptagon–pentagon pairs. We show that at naturally low GB charges the strain field scattering dominates and leads to physically reasonable and, what is important, experimentally observable values of the electrical resistivity. It ranges from 0.1 to 10 k$$\Omega$$
Ω
$$\upmu m$$

μ
m

for different types of symmetric GBs with a size of 1 $$\upmu$$
μ
m and has a strong dependence on misorientation angle. For low-angle highly charged GBs, two scattering mechanisms may compete. The resistivity increases markedly with decreasing GB size and reaches values of 60 k$$\Omega$$
Ω
$$\upmu$$
μ
m and more. It is also very sensitive to the presence of irregularities modeled by embedding of partial disclination dipoles. With significant distortion, we found an increase in resistance by more than an order of magnitude, which is directly related to the destruction of diffraction on the GB. Our findings may be of interest both in the interpretation of experimental data and in the design of electronic devices based on poly- and nanocrystalline graphene.
Survival prediction in triple negative breast cancer using multiple instance learning of histopathological images
Authors: Sandarenu Piumi , Millar Ewan K. A. , Song Yang , Browne Lois , Beretov Julia , Lynch Jodi , Graham Peter H. , Jonnagaddala Jitendra , Hawkins Nicholas , Huang Junzhou , Meijering Erik 
Published: August 2022

AbstractComputational pathology is a rapidly expanding area for research due to the current global transformation of histopathology through the adoption of digital workflows. Survival prediction of breast cancer patients is an important task that currently depends on histopathology assessment of cancer morphological features, immunohistochemical biomarker expression and patient clinical findings. To facilitate the manual process of survival risk prediction, we developed a computational pathology framework for survival prediction using digitally scanned haematoxylin and eosin-stained tissue microarray images of clinically aggressive triple negative breast cancer. Our results show that the model can produce an average concordance index of 0.616. Our model predictions are analysed for independent prognostic significance in univariate analysis (hazard ratio = 3.12, 95% confidence interval [1.69,5.75], p < 0.005) and multivariate analysis using clinicopathological data (hazard ratio = 2.68, 95% confidence interval [1.44,4.99], p < 0.005). Through qualitative analysis of heatmaps generated from our model, an expert pathologist is able to associate tissue features highlighted in the attention heatmaps of high-risk predictions with morphological features associated with more aggressive behaviour such as low levels of tumour infiltrating lymphocytes, stroma rich tissues and high-grade invasive carcinoma, providing explainability of our method for triple negative breast cancer.
Scraping nasal cytology in the diagnostics of rhinitis and the comorbidities
Authors: Myszkowska Dorota , Bazgier Monika , Brońska Sara , Nowak Karol , Ożga Joanna , Woźniak Aleksandra , Stanisz Andrzej , Szaleniec Joanna 
Published: August 2022

AbstractNasal scraping cytology is a non-invasive tool used in the diagnostics of allergic and non-allergic rhinitis. The study aimed to analyze to what extent the cytological picture of the nasal mucosa coincides with the diagnosis of a given disease, taking into account the content of eosinophils. Retrospective analysis of the cytograms performed in 842 patients was carried out in relation to the disease entities and the content of eosinophils. Significant relationship between the Epith:Infl ratio and the four groups of diseases (Chi2 = 9.6488; p = .014) was confirmed. The more intensive inflammation was found, the higher percentage of patients had manifested the increased level of eosinophils (> 1% in the inflammatory cells). The value of 20% of eosinophils in all counted cells corresponds to around 45% of eosinophils in the inflammatory cells in patients with the evident inflammatory picture. Allergic rhinitis presents a different cytological picture regarding the eosinophilic reaction against the background of the inflammation process: the higher degree of inflammation observed, the lower amount of eosinophils detected, with the exception of allergic rhinitis provoked by pollen allergens.
Fire and termite resistance of wood treated with PF6-based ionic liquids
Authors: Miyafuji Hisashi , Minamoto Koji 
Published: August 2022

AbstractSix PF6-based ionic liquids (ILs) were investigated to evaluate their potential as chemicals for enhancing fire and termite resistance of wood. The ILs used in this study included 1-methyl-1-propylpyrrolidinium hexafluorophosphate ([MPPL]PF6), 1-methyl-1-propylpiperidinium hexafluorophosphate ([MPPR]PF6), 1-ethyl-3-methylimidazolium hexafluorophosphate ([EMIM]PF6), tetrabutylphosphonium hexafluorophosphate ([TBP]PF6), trihexyltetradecylphosphonium hexafluorophosphate ([THP]PF6), and 1-butylpyridinium hexafluorophosphate ([BPYR]PF6). All of the IL-treated wood samples did not undergo any morphological changes, and exhibited enhanced fire- and termite resistance compared with untreated wood. The fire resistance properties of all of the prepared IL-treated wood specimens were comparable. However, the [EMIM]PF6- and [THP]PF6-treated wood showed slightly inferior termite resistance among the tested IL-treated woods. Overall, [TBP]PF6 was the most promising candidate among the evaluated PF6-based ILs because it is stable in wood without leaching after water penetration.
An early prediction model for canine chronic kidney disease based on routine clinical laboratory tests
Authors: Kokkinos Yiannis , Morrison JoAnn , Bradley Richard , Panagiotakos Theodoros , Ogeer Jennifer , Chew Dennis , O’Flynn Ciaran , De Meyer Geert , Watson Phillip , Tagkopoulos Ilias 
Published: August 2022

AbstractThe aim of this study was to derive a model to predict the risk of dogs developing chronic kidney disease (CKD) using data from electronic health records (EHR) collected during routine veterinary practice. Data from 57,402 dogs were included in the study. Two thirds of the EHRs were used to build the model, which included feature selection and identification of the optimal neural network type and architecture. The remaining unseen EHRs were used to evaluate model performance. The final model was a recurrent neural network with 6 features (creatinine, blood urea nitrogen, urine specific gravity, urine protein, weight, age). Identifying CKD at the time of diagnosis, the model displayed a sensitivity of 91.4% and a specificity of 97.2%. When predicting future risk of CKD, model sensitivity was 68.8% at 1 year, and 44.8% 2 years before diagnosis. Positive predictive value (PPV) varied between 15 and 23% and was influenced by the age of the patient, while the negative predictive value remained above 99% under all tested conditions. While the modest PPV limits its use as a stand-alone diagnostic screening tool, high specificity and NPV make the model particularly effective at identifying patients that will not go on to develop CKD.
Airway epithelial immunoproteasome subunit LMP7 protects against rhinovirus infection
Authors: Dimasuay Kris Genelyn , Schaunaman Niccolette , Berg Bruce , Cervantes Diana , Kruger Elke , Heppner Frank L. , Ferrington Deborah A. , Chu Hong Wei 
Published: August 2022

AbstractImmunoproteasomes (IP) serve as an important modulator of immune responses to pathogens and other pathological factors. LMP7/β5i, one of the IP subunits, plays a critical role in autoimmune diseases by downregulating inflammation. Rhinovirus (RV) infection is a major risk factor in the exacerbations of respiratory inflammatory diseases, but whether LMP7 regulates RV-mediated inflammation in the lung particularly in the airway epithelium, the first line of defense against RV infection, remains unclear. In this study, we determined whether airway epithelial LMP7 promotes the resolution of RV-mediated lung inflammation. Inducible airway epithelial-specific LMP7-deficient (conditional knockout, CKO) mice were generated to reveal the in vivo anti-inflammatory and antiviral functions of LMP7. By using LMP7-deficient primary human airway epithelial cells generated by CRISPR-Cas9, we confirmed that airway epithelial LMP7 decreased pro-inflammatory cytokines and viral load during RV infection. Additionally, airway epithelial LMP7 enhanced the expression of a negative immune regulator A20/TNFAIP3 during viral infection that may contribute to the anti-inflammatory function of LMP7. We also discovered that induction of LMP7 by a low dose of polyinosinic:polycytidylic acid (PI:C) reduced RV-mediated inflammation in our CKO mice infected with RV. Our findings suggest that airway epithelial LMP7 has anti-inflammatory and antiviral functions that is critical to the resolution of RV-mediated lung inflammation. Induction of airway epithelial LMP7 may open a novel avenue for therapeutic intervention against RV infection.
A metasurface composed of orifice-type unit cells for the redirection of acoustic waves
Authors: Park Choon Mahn , Yim Geo-Su , Lee Sang Hun 
Published: August 2022

AbstractTo implement a sound wave redirection system, a two-dimensional (2D) slice of a three-dimensional (3D) metasurface is designed and fabricated using a one-dimensional (1D) face-centred orifice cubic (FCOC) unit cell. The metasurface consists of five identical periodic groups, of which one periodic group consists of eight unit-cell groups with a phase shift of $$\pi /4$$

π
/
4

adjacent to each other. One unit-cell group consists of four 1D FCOC unit cells with the same orifice diameter. From the numerical simulation results of the designed metasurface, we observed the redirections of sound waves and compared them with the expected theoretical results. It was confirmed that the experimental results agree well with the simulated results with respect to the different incident angles and frequencies. The used frequencies that satisfy the homogeneous medium condition of the metamaterial for the redirection of incident waves range between 1500 and 2700 Hz. At the characteristic frequency of 1540 Hz at normal incidence, it is considered that stationary evanescent waves exist at the boundary of the metasurface due to the characteristics of the surface wave and the limited end boundary. The FCOC-based metasurface provides a new method of metasurface fabrication and is expected to expand the applicability of the metasurface because it can be easily applied to a surface with any shape.
An automated deep learning method and novel cardiac index to detect canine cardiomegaly from simple radiography
Authors: Jeong Yeojin , Sung Joohon 
Published: August 2022

AbstractSince most of degenerative canine heart diseases accompany cardiomegaly, early detection of cardiac enlargement is main priority healthcare issue for dogs. In this study, we developed a new deep learning-based radiographic index quantifying canine heart size using retrospective data. The proposed “adjusted heart volume index” (aHVI) was calculated as the total area of the heart multiplied by the heart’s height and divided by the fourth thoracic vertebral body (T4) length from simple lateral X-rays. The algorithms consist of segmentation and measurements. For semantic segmentation, we used 1000 dogs’ radiographic images taken between Jan 2018 and Aug 2020 at Seoul National University Veterinary Medicine Teaching Hospital. The tversky loss functions with multiple hyperparameters were used to capture the size-unbalanced regions of heart and T4. The aHVI outperformed the current clinical standard in predicting cardiac enlargement, a common but often fatal health condition for small old dogs.
Members of Venezuelan Equine Encephalitis complex entry into host cells by clathrin-mediated endocytosis in a pH-dependent manner
Authors: Ghietto Lucia Maria , Gil Pedro Ignacio , Olmos Quinteros Paloma , Gomez Emiliano , Piris Franco Martin , Kunda Patricia , Contigiani Marta , Paglini Maria Gabriela 
Published: August 2022

AbstractPixuna virus (PIXV) and Río Negro virus (RNV) are mosquito-borne alphaviruses belonging to the Venezuelan Equine Encephalitis (VEE) complex, which includes pathogenic epizootic and enzootic subtypes responsible for life-threatening diseases in equines. Considering that the first steps in viral infection are crucial for the efficient production of new progeny, the aim of this study was to elucidate the early events of the replication cycle of these two viruses. To this end, we used chemical inhibitors and the expression of dominant-negative constructs to study the dependence of clathrin and endosomal pH on PIXV and RNV internalization mechanisms. We demonstrated that both viruses are internalized primarily via clathrin-mediated endocytosis, where the low pH in endosomes is crucial for viral replication. Contributing knowledge regarding the entry route of VEE complex members is important to understand the pathogenesis of these viruses and also to develop new antiviral strategies.
Life cycle impact assessment and life cycle cost assessment for centralized and decentralized wastewater treatment plants in Thailand
Authors: Prateep Na Talang Rutjaya , Sirivithayapakorn Sanya , Polruang Sucheela 
Published: August 2022

AbstractThis research investigates the cost-effectiveness of four sludge treatment scenarios for centralized (C) and decentralized (D) wastewater treatment plants (WWTP) using life cycle cost assessment (LCCA). The environmental impacts and costs are quantified by Stepwise2006. The most environmentally and financially viable WWTP construction option for Bangkok, Thailand (2022–2031) is determined in terms of LCCA and net present value (NPV). The environmental costs of D-treatment scenarios are lower than those of C-treatment scenarios. The total environmental costs of C- and D-fertilizer scenarios are lower than those of C- and D-dewatering scenarios. The net cash flow per functional unit of C-WWTPs is higher than that of D-WWTPs. The C-fertilizer scenario is the most environmentally and economically viable treatment scenario due to the lowest LCCA deficit (−5.58 THB2020 per m3 treated effluent). Composting should thus be adopted for treating sludge. The most environmentally and financially viable WWTP construction option is option I (building four C-WWTPs within 10 years) due to the lowest LCCA deficit (−19925 million THB2020) and smallest financial loss (NPV = −6309.96 million THB2020). Essentially, the local administration of the capital should adopt option I as a guideline in formulating the wastewater treatment management policy of 2022–2031.