Miracle-dz/UniFAR-FTUs huggingface dataset:
Toripalimab: the First Domestic Anti-Tumor PD-1 Antibody in China

Toripalimab (Tuoyi™) is a selective, recombinant, humanized monoclonal antibody against programmed death protein 1 (PD-1) developed by Shanghai Junshi Bioscience Co., Ltd. Toripalimab is able to bind to PD-1 and block the interaction with its ligands. The binding of toripalimab to PD-1 is mainly attributed to the heavy chain of the former and the FG loop of the latter. Toripalimab received a conditional approval in China for the treatment of melanoma (second-line) in December, 2018. It has also received approvals to treat nasopharyngeal carcinoma (first-line and third-line) and urothelial carcinoma (second-line) in 2021. Additionally, several orphan drug designations were granted to toripalimab by the US Food and Drug Administration. Toripalimab has exhibited primary anti-tumor effects in tumors such as melanoma, lung cancer, digestive tract tumors, hepatobiliary and pancreatic tumors, neuroendocrine neoplasms, nasopharyngeal carcinoma and urothelial carcinoma. It showed a satisfactory anti-tumor effect and long-term survival benefits in Chinese melanoma patients, while the combination of axitinib with toripalimab exhibited an impressive result in metastatic mucosal melanoma. As a checkpoint inhibitor, toripalimab was generally well-tolerated in the enrolled patients. Due to different study populations, comparisons could not be made directly between toripalimab and other drugs in most cases. Nevertheless, the introduction of toripalimab may offer a valuable choice for decision-making in the treatment of tumors in the future.
Differences and Similarities in Motives to Decrease Drinking, and to Drink in General Between Former and Current Heavy Drinkers—Implications for Changing Own Drinking Behaviour

The evidence on why people initiate or cease drinking is vast; however, little is known regarding why people change their frequency and amount of drinking from intense (heavy or dependent drinking) to recreational (with little risk). Therefore, the purpose of this study was to investigate how drinking motives and motives to decrease drinking differ between former heavy drinkers (problematic and dependent), current dependent, and current recreational drinkers. Data were obtained from four groups of individuals (n = 263) using alcohol with different severity. The participants were Polish young adults aged between 18 and 35 years. About 53% of the sample were women. The Alcohol Use Disorder Identification Test (AUDIT) was used to assess the level of drinking; the Drinking Motive Questionnaire-Revised Short Form (DMQ-R SF) was used to assess drinking motives (social, coping, enhancement, and conformity). The reasons for abstaining and limiting drinking (RALD) instrument was used to assess the RALD. Additionally, a set of questions regarding motives to decrease drinking were analysed. The results show that differences were observed between the investigated groups: the current dependent group scored significantly higher on all the dimensions of drinking motives than the current low-risk group and significantly higher on coping, social, and enhancement motives than former heavy drinkers (both groups). The two groups of former heavy drinkers did not differ from each other on drinking motives. The investigated groups differed on the motives to reduce drinking—low-risk users scored the lowest on all the motives, whereas current dependent—the highest. The differences in motives to decrease drinking between current-depended and former heavy drinkers indicate which motives can be associated with the prevention strategies, programmes, and therapeutic approaches.
[18F] Sodium Fluoride Dose Reduction Enabled by Digital Photon Counting PET/CT for Evaluation of Osteoblastic Activity

The aim of the study was to assess the quality and reproducibility of reducing the injected [18F] sodium fluoride ([18F]NaF) dose while maintaining diagnostic imaging quality in bone imaging in a preclinical skeletal model using digital photon counting PET (dPET) detector technology. Beagles (n = 9) were administered three different [18F]NaF doses: 111 MBq (n = 5), 20 MBq (n = 5), and 1.9 MBq (n = 9). Imaging started ≃45 min post-injection for ≃30 min total acquisition time. Images were reconstructed using Time-of-Flight, ultra-high definition (voxel size of 1 × 1 × 1 mm3), with 3 iterations and 3 subsets. Point spread function was modeled and Gaussian filtering was applied. Skeleton qualitative and quantitative molecular image assessment was performed. The overall diagnostic quality of all images scored excellent (61%) and acceptable (39%) by all the reviewers. [18F]NaF SUVmean showed no statistically significant differences among the three doses in any of the region of interest assessed. This study demonstrated that a 60-fold [18F]NaF dose reduction was not significantly different from the highest dose, and it had not significant effect on overall image quality and quantitative accuracy. In the future, ultra-low dose [18F]NaF dPET/CT imaging may significantly decrease PET radiation exposure to preclinical subjects and personnel.
Enhanced Catalytic Activity of Boron Nitride Nanotubes by Encapsulation of Nickel Wire Toward O2 Activation and CO Oxidation: A Theoretical Study

Perfect boron nitride (BN) nanotubes are chemically inert, and hardly considered as catalysts. Nevertheless, metal wire encapsulated BN nanotubes show extraordinarily high chemical activity. We report nickel (Ni) nanowire encapsulated BN(8.0) and BN(9.0) nanotubes toward O2 activation and CO oxidization on the basis of first-principles calculations. Our results suggest that Ni wire encapsulated BN(8.0) and BN(9.0) nanotubes can easily adsorb and activate O2 molecules to form peroxo or superoxo species exothermically. Meanwhile, superoxo species are ready to react with CO molecules forming OCOO intermediate state and finally yielding CO2 molecules. Meanwhile, the rate-limiting step barrier is only 0.637 eV, implying excellent performance for CO oxidation on Ni nanowire encapsulated BN nanotubes. Furthermore, encapsulation of nickel wire improves the catalytic activity of BN nanotubes by facilitating electron transfer from Ni wire to BN nanotubes, which facilitates the adsorption of highly electronegative O2 molecules and subsequent CO oxidation. This study provides a practical and efficient strategy for activating O2 on a metal encapsulated BN nanotube toward CO oxidation.
Oral Health-Related Quality of Life in Patients With Chronic Respiratory Diseases—Results of a Systematic Review

Background: This systematic review evaluates the oral health-related quality of life (OHRQoL) of patients with chronic respiratory diseases. Methods: A systematic literature search was performed based on the PubMed, Medline, Web of Science, and Scopus, using the search terms: “oral health-related quality of life” and “respiratory disease” or “lung” and “oral health-related quality of life. ” Full-text articles published until June 30, 2021 and reporting any OHRQoL measurement in children or adults with a chronic respiratory disease or condition were included and analyzed qualitatively. Results: A total of seven out of 44 studies were included, of which four studies examined adults and three studies investigated children. The respective diseases were chronic obstructive pulmonary disease (COPD) (n = 2), sleep apnea (n = 2), severe asthma (n = 1), cystic fibrosis (n = 1), and lung transplantation (n = 1). Four studies confirmed a worse OHRQoL in the respiratory diseased group compared to healthy controls. The overall OHRQoL was reduced in the included studies. Oral health, health-related quality of life, and disease-related parameters were rarely examined with regard to OHRQoL. Conclusion: Patients with chronic respiratory diseases show a reduced OHRQoL. Oral health should be fostered in these individuals to support their OHRQoL.
Oridonin Alleviates LPS-Induced Depression by Inhibiting NLRP3 Inflammasome via Activation of Autophagy

Objective: Oridonin (Ori) is a diterpene compound that has multiple biological properties. Here, our study was conducted to observe the therapeutic effect of Ori on depression as well as to uncover the mechanism. Methods: Lipopolysaccharide (LPS)-induced depression models were established both in C57BL/6 mice and primary astrocytes, which were treated with Ori, autophagy agonist Rapamycin (Rap) and autophagy inhibitor 3-Methyladenine (3-MA). The depressive-like behaviors were assessed with behavioral tests. Autophagy was evaluated in the hippocampus and astrocytes by investigating autophagosomes under transmission electron microscope (TEM) and detecting LC3II/I, Beclin1 and P62 through western blotting. Astrocyte marker glial fibrillary acidic protein (GFAP) was investigated by immunofluorescence. NLRP3 inflammasome activation was evaluated by detecting IL-1β, NLRP3, ASC and Caspase-1 expression and reactive oxygen species (ROS) accumulation was quantified via DCFH-DA probe. Autolysosomes, autophagosomes and mitophagy were separately observed through mTag-Wasabi-LC3 plasmid, MitoTracker Deep Red staining, and TEM. Results: Our results showed that Ori administration alleviated LPS-induced depressive-like behaviors and increased GFAP expression in the hippocampus. Furthermore, Ori treatment promoted autophagy activation and cell viability as well as weakened NLRP3 inflammasome activation and ROS accumulation both in LPS-induced mice and astrocytes. Ori promoted the autophagic flux unblocked through enhancing fusion of autophagosomes with lysosomes as well as enhanced mitophagy in LPS-treated astrocytes. The therapeutic effect of Ori was enhanced by Rap and weakened by 3-MA. Conclusion: Collectively, our findings provided a promising antidepressant drug and uncovered that Ori alleviated LPS-induced depression by inhibiting NLRP3 inflammasome through activation of autophagy.
Keep Calm and Do Not Carry-Forward: Toward Sensor-Data Driven AI Agent to Enhance Human Learning

The integration of Multimodal Data (MMD) and embodied learning systems (such as Motion Based Educational Games, MBEG), can help learning researchers to better understand the synergy between students' interactions and their learning experiences. Unfolding the dynamics behind this important synergy can lead to the design of intelligent agents which leverage students' movements and support their learning. However, real-time use of student-generated MMD derived from their interactions with embodied learning systems (MBEG in our case) is challenging and remains under-explored due to its complexity (e.g., handle sensor-data and enable an AI agent to use them). To bridge this gap, we conducted an in-situ study where 40 children, aged 9–12, played MBEG on maths and language development. We automatically, unobtrusively, and continuously monitored students' experiences using eye-tracking glasses, physiological wristbands, and Kinect, during game-play. This allowed us to understand the different cognitive and physiological dimensions of students' progress (right/wrong responses) during the three different stages of the MBEG problem-solving processes, namely the “see-solve-move-respond” (S2MR) cycle. We introduce the novel Carry Forward Effect (CFE); a phenomenon occurring in such games, whereby students propagate, or “carry forward,” the cognitive and physiological effects derived from their MMD, to subsequent phases in the see-solve-move-respond cycle. By identifying moments when the Carry Forward Effect is congruent (or not) to students' learning performance, we uncover opportunities for feedback delivery to encourage or subdue the impact of the CFE. Our results demonstrate the importance of wristband and eye-tracking data as key indicators for prioritizing adaptive feedback to support students in MBEG and emphasize the significance of using MMD to support students' performance in real-time educational settings.
A SIMPLIFIED PRACTICAL METHOD FOR EVALUATING LIQUEFACTION-INDUCED FLOW

液状化に伴って生じる地盤の流動を線形の有限要素法により簡易的に評価する手法を提案している. 流動を液状化後ゆっくりと生じる現象と想定し, 繰返しせん断応力を加えて液状化させた後単調に載荷させる実験を行い, 液状化後の砂の応力-ひずみ関係を求めたところ, 剛性が非常に小さい, 微小抵抗領域とその後の剛性回復領域に分けられることが分かった. これらをそれぞれ線形の関係に置くことで, 簡易解析に用いる砂の応力-ひずみ関係をモデル化した. さらに, 液状化層上部の非液状化層やケーソン直下の地盤についても線形の応力-ひずみ関係にモデル化する方法を提案した. これらを用いて, 地震被害解析を行ったところ, かなりの精度で実被害を説明できることが分かった.
Does the Use of Complex Sentences Differentiate Between Bilinguals With and Without DLD? Evidence From Conversation and Narrative Tasks

Over-identification of language disorder among bilingual children with typical development (TD) is a risk factor in assessment. One strategy for improving assessment accuracy with bilingual children is to determine which linguistic sub-domains differentiate bilingual children with TD from bilingual children with developmental language disorder (DLD). To date, little research on sequential bilinguals with TD and DLD has focussed on complex (multi-clausal) sentences in naturalistic production, even though this is a noted domain of weakness for school-age monolinguals with DLD. Accordingly, we sought to determine if there were differences in the use of complex sentences in conversational and narrative tasks between school-age sequential bilinguals with TD and with DLD at the early stages of L2 acquisition. We administered a conversation and a narrative task to 63 English L2 children with TD and DLD, aged 5–7 years with 2 years of exposure to the L2. Children had diverse first language backgrounds. The L2-TD and L2-DLD groups were matched for age, length of L2 exposure and general L2 proficiency (receptive vocabulary size). Language samples from both tasks were coded and analyzed for the use of complex versus simple sentences, for the distribution of complex sentence types, for clausal density and mean length of utterance (MLU). Complex sentences included coordinated clauses, sentential complement clauses, adverbial clauses and relative clauses. Using regression modelling and PERMANOVA, we found that the L2-TD group produced more complex sentences than the L2-DLD group, with coordinated clauses, adverbial clauses and relative clauses differing the most between the groups. Furthermore, the two groups differed for mean clausal density, but not for MLU, indicating that clausal density and MLU did not estimate identical morphosyntactic abilities. Individual variation in complex sentence production for L2-TD was predicted by longer L2 exposure and task; by contrast, for L2-DLD, it was predicted by older age. This study indicates that complex sentence production is an area of weakness for bilingual children with DLD, as it is for monolinguals with DLD. The clinical implications of these findings are discussed.
A deep learning-based approach for segmenting and counting reproductive organs from digitized herbarium specimen images using refined Mask Scoring R-CNN

The accurate segmentation and counting of the reproductive organs within the herbarium specimen play an important role in studying the impact of climate change on plant development over time. Recently, the researchers have gained a lot of knowledge about plant phenology owing to herbaria’s digitization efforts, which may help accelerate plant phenology research by making large digitized specimen collections publicly available. Nevertheless, the automatic segmentation and counting of the reproductive organs is a challenging problem. This is because of the high variability of reproductive organs, which vary in size, shape, orientation, and color. The use of machine learning techniques, including deep learning, has recently been shown to be helpful in this endeavor. We proposed in this paper a deep learning method based on the refined Mask Scoring R-CNN approach to segment and count reproductive organs, including buds, flowers, and fruits from specimen images. Our proposed method achieved a precision rate of 94.5% and a recall rate of 93%.
The Influence of Aging on the Functional Connectivity of the Human Basal Ganglia

Although basal ganglia (BG) are involved in the motor disorders of aged people, the effect of aging on the functional interaction of BG is not well-known. This work was aimed at studying the influence of aging on the functional connectivity of the motor circuit of BG (BGmC). Thirty healthy volunteers were studied (young-group 26.4 ± 5.7 years old; aged-group 63.1 ± 5.8 years old) with a procedure planned to prevent the spurious functional connectivity induced by the closed-loop arrangement of the BGmC. BG showed different functional interactions during the inter-task intervals and when subjects did not perform any voluntary task. Aging induced marked changes in the functional connectivity of the BGmC during these inter-task intervals. The finger movements changed the functional connectivity of the BG, these modifications were also different in the aged-group. Taken together, these data show a marked effect of aging on the functional connectivity of the BGmC, and these effects may be at the basis of the motor handicaps of aged people during the execution of motor-tasks and when they are not performing any voluntary motor task.
Generation of Porcine Induced Neural Stem Cells Using the Sendai Virus

The reprogramming of cells into induced neural stem cells (iNSCs), which are faster and safer to generate than induced pluripotent stem cells, holds tremendous promise for fundamental and frontier research, as well as personalized cell-based therapies for neurological diseases. However, reprogramming cells with viral vectors increases the risk of tumor development due to vector and transgene integration in the host cell genome. To circumvent this issue, the Sendai virus (SeV) provides an alternative integration-free reprogramming method that removes the danger of genetic alterations and enhances the prospects of iNSCs from bench to bedside. Since pigs are among the most successful large animal models in biomedical research, porcine iNSCs (piNSCs) may serve as a disease model for both veterinary and human medicine. Here, we report the successful generation of piNSC lines from pig fibroblasts by employing the SeV. These piNSCs can be expanded for up to 40 passages in a monolayer culture and produce neurospheres in a suspension culture. These piNSCs express high levels of NSC markers (PAX6, SOX2, NESTIN, and VIMENTIN) and proliferation markers (KI67) using quantitative immunostaining and western blot analysis. Furthermore, piNSCs are multipotent, as they are capable of producing neurons and glia, as demonstrated by their expressions of TUJ1, MAP2, TH, MBP, and GFAP proteins. During the reprogramming of piNSCs with the SeV, no induced pluripotent stem cells developed, and the established piNSCs did not express OCT4, NANOG, and SSEA1. Hence, the use of the SeV can reprogram porcine somatic cells without first going through an intermediate pluripotent state. Our research produced piNSCs using SeV methods in novel, easily accessible large animal cell culture models for evaluating the efficacy of iNSC-based clinical translation in human medicine. Additionally, our piNSCs are potentially applicable in disease modeling in pigs and regenerative therapies in veterinary medicine.
Assessing the Long-term Success of Reigate Stone Conservation at Hampton Court Palace and the Tower

Reigate stone was extensively used in medieval London and is prone to rapid decay. A variety of different conservation treatments has been applied in the past; in many cases, these have not mitigated on-going decay. This paper presents an overview of wax, limewash, silane and ammonium tartrate treatment at the Tower of London and Hampton Court Palace. Documentary analysis and visual inspection indicate that whilst these methods have provided protection to some stones, no single method has resulted in the protection of all stones. Non-destructive and minimally-destructive testing is used to more closely assess the effects of ammonium tartrate treatment. The results imply that inherent stone mineralogy, past decay pathways and/or present environmental factors are a greater influence on ongoing decay than treatment histories. ARTICLE HISTORY Received June 2019 Accepted March 2020
SGP-C: A Broad Host Range Temperate Bacteriophage; Against Salmonella gallinarum

Salmonella gallinarum is a poultry restricted-pathogen causing fowl-typhoid disease in adult birds with mortality rates up-to 80% and exhibit resistance against commonly used antibiotics. In this current study, a temperate broad host range bacteriophage SGP-C was isolated against S. gallinarum from poultry digesta. It showed infection ability in all the 15 tested field strains of S. gallinarum. The SGP-C phage produced circular, turbid plaques with alternate rings. Its optimum activity was observed at pH 7.0 and 37–42°C, with a latent period of 45 min and burst size of 187 virions/bacterial cell. The SGP-C lysogens, SGPC-L5 and SGPC-L6 exhibited super-infection immunity against the same phage, an already reported feature of lysogens. A virulence index of 0.5 and 0.001 as MV50 of SGP-C suggests its moderate virulence. The genome of SGP-C found circular double stranded DNA of 42 Kbp with 50.04% GC content, which encodes 63 ORFs. The presence of repressor gene at ORF49, and absence of tRNA sequence in SGP-C genome indicates its lysogenic nature. Furthermore, from NGS analysis of lysogens we propose that SGP-C genome might exist either as an episome, or both as integrated and temporary episome in the host cell and warrants further studies. Phylogenetic analysis revealed its similarity with Salmonella temperate phages belonging to family Siphoviridae. The encoded proteins by SGP-C genome have not showed homology with any known toxin and virulence factor. Although plenty of lytic bacteriophages against this pathogen are already reported, to our knowledge SGP-C is the first lysogenic phage against S. gallinarum reported so far.
Gfi1aa/Lsd1 Facilitates Hemangioblast Differentiation Into Primitive Erythrocytes by Targeting etv2 and sox7 in Zebrafish

The first wave of hematopoiesis is the primitive hematopoiesis, which produces embryonic erythroid and myeloid cells. Primitive erythrocytes are thought to be generated from bipotent hemangioblasts, but the molecular basis remains unclear. Transcriptional repressors Gfi1aa and Gfi1b have been shown to cooperatively promote primitive erythrocytes differentiation from hemangioblasts in zebrafish. However, the mechanism of these repressors during the primitive wave is largely unknown. Herein, by functional analysis of zebrafish gfi1aa smu10 , gfi1b smu11 , gfi1ab smu12 single, double, and triple mutants, we found that Gfi1aa not only plays a predominant role in primitive erythropoiesis but also synergizes with Gfi1ab. To screen Gfi1aa downstream targets, we performed RNA-seq and ChIP-seq analysis and found two endothelial transcription factors, etv2 and sox7, to be repressed by Gfi1aa. Genetic analysis demonstrated Gfi1aa to promote hemangioblast differentiation into primitive erythrocytes by inhibiting both etv2 and sox7 in an Lsd1-dependent manner. Moreover, the H3K4me1 level of etv2 and sox7 were increased in gfi1aa mutant. Taken together, these results suggest that Gfi1aa/Lsd1-dependent etv2/sox7 downregulation is critical for hemangioblast differentiation during primitive hematopoiesis by inhibition of endothelial specification. The different and redundant roles for Gfi1(s), as well as their genetic and epigenetic regulation during primitive hematopoiesis, help us to better know the molecular basis of the primitive hematopoiesis and sheds light on the understanding the Gfi1(s) related pathogenesis.