bluuebunny/crossref_metadata_2025 huggingface dataset:
State Responsibility for International Bail Jumping
Authors: CURRIE ROBERT J. , MATHESON ELIZABETH
Published: July 2022

Over the last decade, there has been a spate of incidents in Canada and the United States involving Saudi Arabian nationals who, while out on bail for predominantly sexual crimes, were able to abscond from the countries despite having surrendered their passports. Investigation has revealed evidence supporting a reasonable inference that the government of Saudi Arabia has, in fact, assisted its nationals to escape on these occasions. This article makes the case that this kind of conduct amounts not just to unfriendly acts but also to infringements upon the territorial sovereignty of both states and serious breaches of the international law of jurisdiction. It surveys the possible remedies available to both injured states and, in light of the fact that neither state has sought any such remedy, examines possible remedial routes for the victims of the Saudi nationals’ crimes. It remarks upon the utter failure of either Canada or the United States to address these acts, concluding that such wilful neglect both corrodes sovereignty and undermines the will to address sexual crimes.
Climate Change and International Legal Personality: “Climate Deterritorialized Nations” as Emerging Subjects of International Law?
Authors: LAPAŠ DAVORIN
Published: July 2022

This article deals with the sea level rise phenomenon caused by the climate change process and its impact on the statehood of so-called disappearing island states as well as on the consequent factual and legal status of their populations. In classical international law doctrine, the loss of a state’s territory will lead to the extinction of statehood and, consequently, the loss of that state’s international legal personality, and possibly also to the statelessness of its nationals. This article proposes an alternative solution based on the transformation of disappearing island states into new non-territorial subjects of international law — “climate deterritorialized nations” — as successors to disappeared inundated states.
Thermoacoustic effects on the propagation of non-planar sound in a circular duct
Authors: Sugimoto Nobumasa
Published: July 2022

This paper examines thermoacoustic effects on the propagation of non-planar sound in a circular duct subjected to an axial temperature gradient. Of particular concern are thermoviscous diffusive effects, which are taken into account by the boundary-layer approximation in a framework of the linear theory. For disturbances expanded into Fourier and Fourier–Bessel series in the azimuthal and radial directions, respectively, the pressure in each mode is described by a one-dimensional, dispersive wave equation, if non-diffusive propagation is assumed. When the diffusive effects are included, each radial mode is coupled to the other radial modes through the boundary layer. Focusing on a single azimuthal and radial mode only, the dispersion relation for the propagation along an infinite duct of a uniform gas is first derived. Effects of the temperature gradient are then examined by solving boundary-value problems for a duct of finite length in four typical cases. Assuming that the wall temperature increases exponentially along the duct, eigenfrequencies and decay rates in the lowest axial mode are obtained as well as axial distributions of the sound pressure and the axial velocity in the duct. The frequency and the decay rate increase as the temperature ratio at both ends becomes higher. It is found from the acoustic energy equation that the dispersion combined with the diffusion acts to reduce the damping and that the temperature gradient makes little contribution to the production of the energy. However, it is unveiled that the non-uniformity in temperature yields thermoacoustic sound confinement in the vicinity of the cold end.
The Failure of “Yugoslavia’s Last Chance”: Ante Marković and his Reformists in the 1990 Elections
Authors: Glaurdić Josip , Filipović Vladimir , Lesschaeve Christophe
Published: July 2022

The last Prime Minister of Yugoslavia Ante Marković was considered by many within the country and in the international community to be Yugoslavia’s last chance for a peaceful transition toward democracy and capitalism. In spite of his popularity, the Reformist party he created failed decisively in the first democratic elections of 1990. We expose the reasons for this failure by analyzing electoral, economic, and sociodemographic data on the level of more than two hundred Yugoslav municipalities where the Reformists put forward their candidates. Our analysis shows that the party’s failure had little to do with the voters’ exposure to the effects of the free market reforms undertaken by Marković’s federal government during this period. Instead, the Reformists’ results were largely determined by the communities’ ethnic makeup and interethnic balance. The Reformists suffered at the hands of a strong negative campaign by the Serbian regime of Slobodan Milošević, and they were squeezed out by the ethnically based parties that benefited from voters behaving strategically in the electoral marketplace dominated by questions of nationalism. The analysis presented here offers important lessons for our understanding of Yugoslavia’s breakup, post-communist transitions in general, and electoral politics in societies on the verge of ethnic conflict.
The dispersion and propagation of topological Langmuir-cyclotron waves in cold magnetized plasmas
Authors: Fu Yichen , Qin Hong
Published: July 2022

The topological Langmuir-cyclotron wave (TLCW) is a recently identified topological surface excitation in magnetized plasmas. We show that TLCW originates from the topological phase transition at the Langmuir wave-cyclotron wave resonance. By isofrequency surface analysis and two- and three-dimensional time-dependent simulations, we demonstrate that the TLCW can propagate robustly along complex phase transition interfaces in a unidirectional manner and without scattering. Because of these desirable features, the TLCW could be explored as an effective mechanism to drive current and flow in magnetized plasmas. The analysis also establishes a close connection between the newly instituted topological phase classification of plasmas and the classical Clemmow-Mullaly-Allis (CMA) diagram of plasma waves.
Integrating morphological and contextual cues in lexical inferencing of Chinese fourth graders
Authors: Zhang Huan , Zhang Jie , Han Chunxiang , Zhou Xuelian , Su Yongqiang , Li Hong
Published: July 2022

The study investigated the strategies used by Chinese students in inferring meanings of unfamiliar words and the influential factors of successful use of different lexical inferencing strategies. A total of 104 fourth graders inferred 36 unfamiliar semitransparent compound words in three conditions: word in isolation, contextual information only, and both word and context. Results revealed that students were more likely to obtain the correct meaning of words when both morphological information and contextual information were available. The likelihood of using a morpheme-based or context-based lexical inferencing strategy was strongly influenced by the presentation condition of target words and precursors. Students with higher vocabulary knowledge and reading comprehension ability were more sensitive to morphological and contextual information and were able to synthesize multiple sources of information, whereas children with lower vocabulary knowledge and reading comprehension ability showed difficulties in integration and tended to overly rely on morphological information. The findings reveal the interactions between available source information and individual differences in vocabulary knowledge and reading comprehension in predicting lexical inferencing and have implications for vocabulary and reading instruction.
Gina Oselio and Opera inFin-de-SiècleNorway
Authors: Sasser Patricia Puckett
Published: July 2022

In 1888, Norwegian newspapers eagerly announced the arrival of ‘Miss Gina Oselio’, who was returning to Norway ‘after seven years of staying abroad’. Oselio (Ingeborg Aas (1858–1937)) had achieved tremendous success as an opera singer in Europe and her performance on the Norwegian concert stage did not disappoint. Her new popularity positioned the singer as a member of the country's cultural elite and introduced a new complexity to her operatic identity. Unlike other Norwegian musicians who were treated primarily in terms of their nationality, her ‘Norwegianness’ had been largely incidental during her career. Oselio's private papers, however, offer new insights into the complex relationship between the singer and the nation. Together with her reception history, these materials invite a fresh examination of Oselio's position infin-de-siècleNorwegian musical life. They show how she cultivated her career and her identity outside Norway, as well as her deliberate decision to assert her ‘Norwegianness’. They demonstrate the roles that Oselio wished to occupy on the country's stages and how other Norwegians responded to these roles. Ultimately, they document a period of transition, as artists, critics and audiences sought to determine the place that opera would occupy within the nation.
Turning a Silk Purse into a Sow's Ear: A Speculative Note on Humay and Humayun in Philadelphia
Authors: SIMPSON MARIANNA SHREVE
Published: July 2022

The Rare Books department at the Free Library of Philadelphia owns a deluxe manuscript of Sa'di's Kulliyat, originally produced in mid-sixteenth century Shiraz and substantially modified in more modern times. Among the alterations was the insertion of a copy of the famous Timurid painting “Humay and Humayun in a garden”, belonging to the Musée des Arts Décoratifs, Paris. The Philadelphia version of the Paris painting was likely based on either a published reproduction or a photograph taken of the original composition when it was on view at the ground-breaking 1910 exhibition “Meisterwerke muhammedanischer Kunst” in Munich. That photographic reproductions could result in pictorial replicas reveals once again the market forces behind the great interest in, demand for, and production of classical Persian painting during the early twentieth century.
Altered neural flexibility in children with attention-deficit/hyperactivity disorder
Authors: Yin Weiyan , Li Tengfei , Mucha Peter J. , Cohen Jessica R. , Zhu Hongtu , Zhu Ziliang , Lin Weili
Published: July 2022

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood, and is often characterized by altered executive functioning. Executive function has been found to be supported by flexibility in dynamic brain reconfiguration. Thus, we applied multilayer community detection to resting-state fMRI data in 180 children with ADHD and 180 typically developing children (TDC) to identify alterations in dynamic brain reconfiguration in children with ADHD. We specifically evaluated MR derived neural flexibility, which is thought to underlie cognitive flexibility, or the ability to selectively switch between mental processes. Significantly decreased neural flexibility was observed in the ADHD group at both the whole brain (raw p = 0.0005) and sub-network levels (p < 0.05, FDR corrected), particularly for the default mode network, attention-related networks, executive function-related networks, and primary networks. Furthermore, the subjects with ADHD who received medication exhibited significantly increased neural flexibility (p = 0.025, FDR corrected) when compared to subjects with ADHD who were medication naïve, and their neural flexibility was not statistically different from the TDC group (p = 0.74, FDR corrected). Finally, regional neural flexibility was capable of differentiating ADHD from TDC (Accuracy: 77% for tenfold cross-validation, 74.46% for independent test) and of predicting ADHD severity using clinical measures of symptom severity (R2: 0.2794 for tenfold cross-validation, 0.156 for independent test). In conclusion, the present study found that neural flexibility is altered in children with ADHD and demonstrated the potential clinical utility of neural flexibility to identify children with ADHD, as well as to monitor treatment responses and disease severity.
PLAA suppresses ovarian cancer metastasis via METTL3-mediated m6A modification of TRPC3 mRNA
Authors: Shen Zhangjin , Gu Lingkai , Liu Yuwan , Wang Lingfang , Zhu Jiawei , Tang Sangsang , Wei Xinyi , Wang Jiaying , Zhang Songfa , Wang Xinyu , Cheng Xiaodong , Xie Xing , Lu Weiguo
Published: July 2022

Wide metastasis contributes to a high death rate in ovarian cancer, and understanding of the molecular mechanism helps to find effective targets for metastatic ovarian cancer therapy. It has been found that phospholipase A2-activating protein (PLAA) is inactivated in some cancers, but its role in cancer metastasis remains unknown. Here, we found that PLAA was significantly downregulated in ovarian cancer highly metastatic cell lines and patients, and the low expression of PLAA was associated with poorer prognosis and high-risk clinicopathological features of patients. PLAA inhibited the migration and invasion of ovarian cancer cells and metastasis of transplanted tumor in the orthotopic xenograft mouse model. Meanwhile, PLAA inhibited metastasis of ovarian cancer by inhibiting transient receptor potential channel canonical 3 (TRPC3)-mediated the intracellular Ca2+ level. Mechanistically, PLAA inhibited methyltransferase-like 3 (METTL3) expression through the ubiquitin-mediated degradation, and METTL3 stabilized TRPC3 mRNA expression via N6-methyladenosine (m6A) modification. Our study verified the function and mechanism of the PLAA-METTL3-TRPC3 axis involved in ovarian cancer metastasis, with a view to providing a potential therapeutic approach for ovarian cancer.
Heterozygotic Brca1 mutation initiates mouse genome instability at embryonic stage
Authors: Wu Xiaobing , Guo Maoni , Cui Jian , Cai Haoyang , Wang San Ming
Published: July 2022

BRCA1 mutation is the genetic predisposition in causing genome instability towards cancer. BRCA1 mutation is predominantly germline inherited at the fertilization. However, when the inherited mutation initiates genome instability in the mutation carriers remains largely elusive. We used a heterozygotic Brca1-knockout mouse as a model to investigate the issue. Through whole-genome sequencing and bioinformatics analysis, we monitored genome status across the developmental stages from embryo to adulthood in the mouse model. We observed that genome instability as reflected by structural variation, indel and copy number variation already appeared at 10.5-day embryo and progressively towards adulthood. We also observed that the genome instability was not linearly accumulated but dynamically changed along the developmental process, affecting many oncogenic genes and pathways including DNA damage repair, estrogen signaling, and oncogenesis. We further observed that many genome abnormalities in the cancer caused by Brca1 mutation were originated at embryonic stage, and Trp53 (TP53) mutation was not essential for the Brca1 mutation-caused genome instability in the non-cancer cells. Our study revealed that heterozygotic Brca1 mutation alone can cause genome instability at embryonic stage, highlighting that prevention of BRCA1 mutation-related cancer in humans may need to start earlier than currently considered.
Small changes in rhizosphere microbiome composition predict disease outcomes earlier than pathogen density variations
Authors: Gu Yian , Banerjee Samiran , Dini-Andreote Francisco , Xu Yangchun , Shen Qirong , Jousset Alexandre , Wei Zhong
Published: July 2022

Even in homogeneous conditions, plants facing a soilborne pathogen tend to show a binary outcome with individuals either remaining fully healthy or developing severe to lethal disease symptoms. As the rhizosphere microbiome is a major determinant of plant health, we postulated that such a binary outcome may result from an early divergence in the rhizosphere microbiome assembly that may further cascade into varying disease suppression abilities. We tested this hypothesis by setting up a longitudinal study of tomato plants growing in a natural but homogenized soil infested with the soilborne bacterial pathogen Ralstonia solanacearum. Starting from an originally identical species pool, individual rhizosphere microbiome compositions rapidly diverged into multiple configurations during the plant vegetative growth. This variation in community composition was strongly associated with later disease development during the later fruiting state. Most interestingly, these patterns also significantly predicted disease outcomes 2 weeks before any difference in pathogen density became apparent between the healthy and diseased groups. In this system, a total of 135 bacterial OTUs were associated with persistent healthy plants. Five of these enriched OTUs (Lysinibacillus, Pseudarthrobacter, Bordetella, Bacillus, and Chryseobacterium) were isolated and shown to reduce disease severity by 30.4–100% when co-introduced with the pathogen. Overall, our results demonstrated that an initially homogenized soil can rapidly diverge into rhizosphere microbiomes varying in their ability to promote plant protection. This suggests that early life interventions may have significant effects on later microbiome states, and highlights an exciting opportunity for microbiome diagnostics and plant disease prevention.
MicroRNA-mediated regulation of lipid metabolism in virus-infected Emiliania huxleyi
Authors: Zhang Enquan , Gao Jingjing , Wei Zehua , Zeng Jun , Li Jian , Li Guiling , Liu Jingwen
Published: July 2022

The interactions between Emiliania huxleyi and E. huxleyi virus (EhV) regulate marine carbon and sulfur biogeochemical cycles and play a prominent role in global climate change. As a large DNA virus, EhV has developed a novel “virocell metabolism” model to meet its high metabolic needs. Although it has been widely demonstrated that EhV infection can profoundly rewire lipid metabolism, the epigenetic regulatory mechanisms of lipid metabolism are still obscure. MicroRNAs (miRNAs) can regulate biological pathways by targeting hub genes in the metabolic processes. In this study, the transcriptome, lipidome, and miRNAome were applied to investigate the epigenetic regulation of lipid metabolism in E. huxleyi cells during a detailed time course of viral infection. Combined transcriptomic, lipidomic, and physiological experiments revealed reprogrammed lipid metabolism, along with mitochondrial dysfunction and calcium influx through the cell membrane. A total of 69 host miRNAs (including 1 known miRNA) and 7 viral miRNAs were identified, 27 of which were differentially expressed. Bioinformatic prediction revealed that miRNAs involved in the regulation of lipid metabolism and a dual-luciferase reporter assay suggested that phosphatidylinositol 3-kinase (PI3K) gene might be a target of ehx-miR5. Further qPCR and western blot analysis showed a significant negative correlation between the expression of ehx-miR5 and its target gene PI3K, along with the lower activity of its downstream components (p-Akt, p-TOR, SREBP), indicating that lipid metabolism might be regulated by ehx-miR5 through the PI3K-Akt-TOR signaling pathway. Our findings reveal several novel mechanisms of viral strategies to manipulate host lipid metabolism and provide evidence that ehx-miR5 negatively modulates the expression of PI3K and disturbs lipid metabolism in the interactions between E. huxleyi and EhV.
Factors affecting the quality of endodontic treatment in general dental practice in Scotland: a qualitative focus group study
Authors: Khamuani Sonia , Ross Alastair , Robertson Douglas
Published: July 2022

Introduction The quality of endodontic treatment worldwide is variable despite clear clinical guidelines being available.

Aims Identify the factors that affect the quality of endodontic treatment in general dental practice in Scotland and how to overcome the barriers identified.

Methods Four online focus group interview sessions were conducted in which a total of 16 participants were recruited, including general dental practitioners, endodontic specialists and educationalists. Topics for facilitated discussion were based on healthcare system theory and included education/training, patient factors, resources and equipment factors; themes were identified via template analysis.

Results A number of themes and subthemes affecting the quality of care are reported, including aspects to do with remuneration, time, education, training, support from secondary care and the impact of COVID-19.

Conclusion Findings support: increase practical experience for undergraduates; access to postgraduate mentoring and training; development of a managed clinical network to facilitate access to appropriately trained specialists; and increased remuneration to allow sufficient time and adequate equipment to achieve clinical standards.
Non-canonical EphA2 activation underpins PTEN-mediated metastatic migration and poor clinical outcome in prostate cancer
Authors: Sachdeva Ashwin , Hart Claire A. , Kim Kyungmin , Tawadros Thomas , Oliveira Pedro , Shanks Jonathan , Brown Mick , Clarke Noel
Published: July 2022

Background

The key process of mesenchymal to amoeboid transition (MAT), which enables prostate cancer (PCa) transendothelial migration and subsequent development of metastases in red bone marrow stroma, is driven by phosphorylation of EphA2S897 by pAkt, which is induced by the omega-6 polyunsaturated fatty acid arachidonic acid. Here we investigate the influence of EphA2 signalling in PCa progression and long-term survival.

Methods

The mechanisms underpinning metastatic biopotential of altered EphA2 signalling in relation to PTEN status were assessed in vitro using canonical (EphA2D739N) and non-canonical (EphA2S897G) PC3-M mutants, interrogation of publicly available PTEN-stratified databases and clinical validation using a PCa TMA (n = 177) with long-term follow-up data. Spatial heterogeneity of EphA2 was assessed using a radical prostatectomy cohort (n = 67).

Results

Non-canonical EphA2 signalling via pEphA2S897 is required for PCa transendothelial invasion of bone marrow endothelium. High expression of EphA2 or pEphA2S897 in a PTENlow background is associated with poor overall survival. Expression of EphA2, pEphA2S897 and the associated MAT marker pMLC2 are spatially regulated with the highest levels found within lesion areas within 500 µm of the prostate margin.

Conclusion

EphA2 MAT-related signalling confers transendothelial invasion. This is associated with a substantially worse prognosis in PTEN-deficient PCa.
SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin
Authors: Feng Daniel , Gao Peng , Henley Nathalie , Dubuissez Marion , Chen Nan , Laurin Louis-Philippe , Royal Virginie , Pichette Vincent , Gerarduzzi Casimiro
Published: July 2022

Renal Cell Carcinoma (RCC) is the most common form of all renal cancer cases, and well-known for its highly aggressive metastatic behavior. SMOC2 is a recently described non-structural component of the extracellular matrix (ECM) that is highly expressed during tissue remodeling processes with emerging roles in cancers, yet its role in RCC remains elusive. Using gene expression profiles from patient samples, we identified SMOC2 as being significantly expressed in RCC tissue compared to normal renal tissue, which correlated with shorter RCC patient survival. Specifically, de novo protein synthesis of SMOC2 was shown to be much higher in the tubular epithelial cells of patients with biopsy-proven RCC. More importantly, we provide evidence of SMOC2 triggering kidney epithelial cells into an epithelial-to-mesenchymal transition (EMT), a phenotype known to promote metastasis. We found that SMOC2 induced mesenchymal-like morphology and activities in both RCC and non-RCC kidney epithelial cell lines. Mechanistically, treatment of RCC cell lines ACHN and 786-O with SMOC2 (recombinant and enforced expression) caused a significant increase in EMT-markers, -matrix production, -proliferation, and -migration, which were inhibited by targeting SMOC2 by siRNA. We further characterized SMOC2 activation of EMT to occur through the integrin β3, FAK and paxillin pathway. The proliferation and metastatic potential of SMOC2 overexpressing ACHN and 786-O cell lines were validated in vivo by their significantly higher tumor growth in kidneys and systemic dissemination into other organs when compared to their respective controls. In principle, understanding the impact that SMOC2 has on EMT may lead to more evidence-based treatments and biomarkers for RCC metastasis.
Mesenchymal/stromal stem cells: necessary factors in tumour progression
Authors: Li Xinyu , Fan Qing , Peng Xueqiang , Yang Shuo , Wei Shibo , Liu Jingang , Yang Liang , Li Hangyu
Published: July 2022

Mesenchymal/stromal stem cells (MSCs) are a crucial component of the tumour microenvironment (TME). They can be recruited from normal tissues into the TME and educated by tumour cells to transform into tumour-associated MSCs, which are oncogenic cells that promote tumour development and progression by impacting or transforming into various kinds of cells, such as immune cells and endothelial cells. Targeting MSCs in the TME is a novel strategy to prevent malignant processes. Exosomes, as communicators, carry various RNAs and proteins and thus link MSCs and the TME, which provides options for improving outcomes and developing targeted treatment.
ACSL4 is essential for radiation-induced intestinal injury by initiating ferroptosis
Authors: Ji Qian , Fu Shengqiao , Zuo Hao , Huang Yumeng , Chu Liangmei , Zhu Yanyan , Hu Jing , Wu Yuting , Chen Shuangwei , Wang Yue , Ren Yongfei , Pu Xi , Liu Na , Li Rongkun , Wang Xu , Dai Chunhua
Published: July 2022

Lipid peroxidation-induced ferroptosis is a newly recognized type of programmed cell death. With the method of RNA sequencing, we found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes, whereas reduced the expression of ferroptosis suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues. By using ferroptosis inducer RSL-3 and inhibitor liproxstatin-1, we found that ferroptosis is essential for IR-induced intestinal injury. Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) is an important component for ferroptosis execution, and we found that ACSL4 expression was significantly upregulated in irradiated intestine tissues, but not in liver or lung tissues. Antibacterial and antifungal regents reduced the expression of ASCL4 and protected against tissue injury in irradiated intestine tissues. Further studies showed that troglitazone, a ACSL4 inhibitor, succeeded to suppresses intestine lipid peroxidation and tissue damage after IR.
Implantable vision-enhancing devices and postoperative rehabilitation in advanced age-related macular degeneration
Authors: Borkenstein Andreas F. , Borkenstein Eva-Maria , Augustin Albert J.
Published: July 2022

Age-related macular degeneration (AMD) results in progressive vision loss that significantly impacts patients’ quality of life and ability to perform routine daily activities. Although pharmaceutical treatments for AMD are available and in clinical development, patients with late-stage AMD are relatively underserved. Specialized rehabilitation programs and external low-vision aids are available to support visual performance for those with advanced AMD; but intraocular vision-improving devices, including implantable miniature telescope (IMT) and intraocular lens (IOL) implants, offer advantages regarding head motion, vestibular ocular reflex development, and depth perception. IMT and IOL technologies are rapidly evolving, and many patients who could benefit from them remain unidentified. This review of recent literature summarizes available information on implantable devices for improving vision in patients with advanced AMD. Furthermore, it discusses recent attempts of developing the quality of life tests including activities of daily life and objective assessments. This may offer the ophthalmologist but also the patient a better possibility to detect changes or improvements before and after surgery. It is evident that surgery with new implants/devices is no longer the challenge, but rather the more complex management of patients before and after surgery as well as the correct selection of cases.
Neurocomputational mechanisms of confidence in self and others
Authors: Bang Dan , Moran Rani , Daw Nathaniel D. , Fleming Stephen M.
Published: July 2022

Computing confidence in one’s own and others’ decisions is critical for social success. While there has been substantial progress in our understanding of confidence estimates about oneself, little is known about how people form confidence estimates about others. Here, we address this question by asking participants undergoing fMRI to place bets on perceptual decisions made by themselves or one of three other players of varying ability. We show that participants compute confidence in another player’s decisions by combining distinct estimates of player ability and decision difficulty – allowing them to predict that a good player may get a difficult decision wrong and that a bad player may get an easy decision right. We find that this computation is associated with an interaction between brain systems implicated in decision-making (LIP) and theory of mind (TPJ and dmPFC). These results reveal an interplay between self- and other-related processes during a social confidence computation.
Accurate somatic variant detection using weakly supervised deep learning
Authors: Krishnamachari Kiran , Lu Dylan , Swift-Scott Alexander , Yeraliyev Anuar , Lee Kayla , Huang Weitai , Leng Sim Ngak , Skanderup Anders Jacobsen
Published: July 2022

Identification of somatic mutations in tumor samples is commonly based on statistical methods in combination with heuristic filters. Here we develop VarNet, an end-to-end deep learning approach for identification of somatic variants from aligned tumor and matched normal DNA reads. VarNet is trained using image representations of 4.6 million high-confidence somatic variants annotated in 356 tumor whole genomes. We benchmark VarNet across a range of publicly available datasets, demonstrating performance often exceeding current state-of-the-art methods. Overall, our results demonstrate how a scalable deep learning approach could augment and potentially supplant human engineered features and heuristic filters in somatic variant calling.
Emergency triage of brain computed tomography via anomaly detection with a deep generative model
Authors: Lee Seungjun , Jeong Boryeong , Kim Minjee , Jang Ryoungwoo , Paik Wooyul , Kang Jiseon , Chung Won Jung , Hong Gil-Sun , Kim Namkug
Published: July 2022

Triage is essential for the early diagnosis and reporting of neurologic emergencies. Herein, we report the development of an anomaly detection algorithm (ADA) with a deep generative model trained on brain computed tomography (CT) images of healthy individuals that reprioritizes radiology worklists and provides lesion attention maps for brain CT images with critical findings. In the internal and external validation datasets, the ADA achieved area under the curve values (95% confidence interval) of 0.85 (0.81–0.89) and 0.87 (0.85–0.89), respectively, for detecting emergency cases. In a clinical simulation test of an emergency cohort, the median wait time was significantly shorter post-ADA triage than pre-ADA triage by 294 s (422.5 s [interquartile range, IQR 299] to 70.5 s [IQR 168]), and the median radiology report turnaround time was significantly faster post-ADA triage than pre-ADA triage by 297.5 s (445.0 s [IQR 298] to 88.5 s [IQR 179]) (all p < 0.001).
Personalized bacteriophage therapy to treat pandrug-resistant spinal Pseudomonas aeruginosa infection
Authors: Ferry T. , Kolenda C. , Laurent F. , Leboucher G. , Merabischvilli M. , Djebara S. , Gustave C.-A. , Perpoint T. , Barrey C. , Pirnay J.-P. , Resch G.
Published: July 2022

Bone and joint infections (BJI) are one of the most difficult-to-treat bacterial infection, especially in the era of antimicrobial resistance. Lytic bacteriophages (phages for short) are natural viruses that can selectively target and kill bacteria. They are considered to have a high therapeutic potential for the treatment of severe bacterial infections and especially BJI, as they also target biofilms. Here we report on the management of a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess who was treated with surgery and a personalized combination of phage therapy that was added to antibiotics. As the infecting P. aeruginosa strain was resistant to the phages developed by private companies that were contacted, we set up a unique European academic collaboration to find, produce and administer a personalized phage cocktail to the patient in due time. After two surgeries, despite bacterial persistence with expression of small colony variants, the patient healed with local and intravenous injections of purified phages as adjuvant therapy.
Construction of the axolotl cell landscape using combinatorial hybridization sequencing at single-cell resolution
Authors: Ye Fang , Zhang Guodong , E. Weigao , Chen Haide , Yu Chengxuan , Yang Lei , Fu Yuting , Li Jiaqi , Fu Sulei , Sun Zhongyi , Fei Lijiang , Guo Qile , Wang Jingjing , Xiao Yanyu , Wang Xinru , Zhang Peijing , Ma Lifeng , Ge Dapeng , Xu Suhong , Caballero-Pérez Juan , Cruz-Ramírez Alfredo , Zhou Yincong , Chen Ming , Fei Ji-Feng , Han Xiaoping , Guo Guoji
Published: July 2022

The Mexican axolotl (Ambystoma mexicanum) is a well-established tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, a process that triggers many dramatic changes in diverse organs, accompanied by gradually decline of their regeneration capacity and lifespan. However, the molecular regulation and cellular changes in neotenic and metamorphosed axolotls are still poorly investigated. Here, we develop a single-cell sequencing method based on combinatorial hybridization to generate a tissue-based transcriptomic landscape of the neotenic and metamorphosed axolotls. We perform gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell landscape. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls reveal the heterogeneity of non-immune parenchymal cells in different tissues and established their regulatory network. Furthermore, we describe dynamic gene expression patterns during limb development in neotenic axolotls. This system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls, serves as a resource to explore the molecular identity of the axolotl and facilitates better understanding of metamorphosis.
A temperature-regulated circuit for feeding behavior
Authors: Qian Shaowen , Yan Sumei , Pang Ruiqi , Zhang Jing , Liu Kai , Shi Zhiyue , Wang Zhaoqun , Chen Penghui , Zhang Yanjie , Luo Tiantian , Hu Xianli , Xiong Ying , Zhou Yi
Published: July 2022

Both rodents and primates have evolved to orchestrate food intake to maintain thermal homeostasis in coping with ambient temperature challenges. However, the mechanisms underlying temperature-coordinated feeding behavior are rarely reported. Here we find that a non-canonical feeding center, the anteroventral and periventricular portions of medial preoptic area (apMPOA) respond to altered dietary states in mice. Two neighboring but distinct neuronal populations in apMPOA mediate feeding behavior by receiving anatomical inputs from external and dorsal subnuclei of lateral parabrachial nucleus. While both populations are glutamatergic, the arcuate nucleus-projecting neurons in apMPOA can sense low temperature and promote food intake. The other type, the paraventricular hypothalamic nucleus (PVH)-projecting neurons in apMPOA are primarily sensitive to high temperature and suppress food intake. Caspase ablation or chemogenetic inhibition of the apMPOA→PVH pathway can eliminate the temperature dependence of feeding. Further projection-specific RNA sequencing and fluorescence in situ hybridization identify that the two neuronal populations are molecularly marked by galanin receptor and apelin receptor. These findings reveal unrecognized cell populations and circuits of apMPOA that orchestrates feeding behavior against thermal challenges.
Functional data-driven framework for fast forecasting of electrode slurry rheology simulated by molecular dynamics
Authors: Duquesnoy Marc , Lombardo Teo , Caro Fernando , Haudiquez Florent , Ngandjong Alain C. , Xu Jiahui , Oularbi Hassan , Franco Alejandro A.
Published: July 2022

The computational simulation of the manufacturing process of lithium-ion battery composite electrodes based on mechanistic models allows capturing the influence of manufacturing parameters on electrode properties. However, ensuring that these properties match with experimental data is typically computationally expensive. In this work, we tackled this costly procedure by proposing a functional data-driven framework, aiming first to retrieve the early numerical values calculated from a molecular dynamics simulation to predict if the observable being calculated is prone to match with our range of experimental values, and in a second step, recover additional values of the ongoing simulation to predict its final result. We demonstrated this approach in the context of the calculation of electrode slurries viscosities. We report that for various electrode chemistries, the expected mechanistic simulation results can be obtained 11 times faster with respect to the complete simulations, while being accurate with a $${R}_{\rm{score}}^{2}$$

R

score

2

equals to 0.96.
Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson’s disease and other synucleinopathies
Authors: Magalhães Pedro , Lashuel Hilal A.
Published: July 2022

Parkinson’s disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10–15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with other neurodegenerative diseases (NDDs) linked to alpha-synuclein (aSyn) aggregation, also called synucleinopathies. Therefore, there is an urgent need to discover and validate early diagnostic and prognostic markers that reflect disease pathophysiology, progression, severity, and potential differences in disease mechanisms between PD and other NDDs. The close association between aSyn and the development of pathology in synucleinopathies, along with the identification of aSyn species in biological fluids, has led to increasing interest in aSyn species as potential biomarkers for early diagnosis of PD and differentiate it from other synucleinopathies. In this review, we (1) provide an overview of the progress toward mapping the distribution of aSyn species in the brain, peripheral tissues, and biological fluids; (2) present comparative and critical analysis of previous studies that measured total aSyn as well as other species such as modified and aggregated forms of aSyn in different biological fluids; and (3) highlight conceptual and technical gaps and challenges that could hinder the development and validation of reliable aSyn biomarkers; and (4) outline a series of recommendations to address these challenges. Finally, we propose a combined biomarker approach based on integrating biochemical, aggregation and structure features of aSyn, in addition to other biomarkers of neurodegeneration. We believe that capturing the diversity of aSyn species is essential to develop robust assays and diagnostics for early detection, patient stratification, monitoring of disease progression, and differentiation between synucleinopathies. This could transform clinical trial design and implementation, accelerate the development of new therapies, and improve clinical decisions and treatment strategies.
Experimental and numerical study of steady state stability in a toluene biodegrading biofilter
Authors: Süß Michael , De Visscher Alex
Published: July 2022

Different steady states in a toluene biodegrading biofilter were explored experimentally and numerically. Experimental results showed that a gradual increase of the toluene inlet concentration over several weeks leads to a consistently low exit concentration, with a drastic increase at an inlet concentration change from 7.7 to 8.5 g m−3, indicating an alteration in steady state. A significant and sudden drop in the removal efficiency from 88 to 46% was observed. A model that includes nitrogen and biomass dynamics predicted results matching the experimental biofilter performance well, but the timing of the concentration jump was not reproduced exactly. A model that assumes a gradual increase of toluene inlet concentration of 0.272 g m−3 per day, accurately reproduced the experimental relationship between inlet and outlet concentration. Although there was variation between experimental and simulated results, a clear confirmation of the jump from one steady state to another was found.
A global equation-of-state model from mathematical interpolation between low- and high-density limits
Authors: Xue Ti-Wei , Guo Zeng-Yuan
Published: July 2022

The ideal gas equation of state (EOS) model is a well-known low-density limiting model. Recently, an ideal dense matter EOS model for the high-density limit symmetric to the ideal gas model has been developed. Here, by mathematically interpolating between the ideal gas and ideal dense matter limiting models, we establish a global model containing two EOS in the form of P-V-T and P-S-T for arbitrary ranges of densities. Different from empirical or semi-empirical EOS, the coefficients in the global EOS have a clear physical meaning and can be determined from a priori knowledge. The proposed global model is thermodynamically consistent and continuous. It reduces to the ideal gas model when approaching the low-density limit and to the ideal dense matter model when approaching the high-density limit. Verifications for 4He show that the global model reproduces the large-range behavior of matter well, along with providing important insight into the nature of the large-range behavior. Compared to the third-order virial EOS and the Benedict–Webb–Rubin EOS, the global P-V-T EOS has higher descriptive accuracy with fewer coefficients over a wide range of data for N2. The global model is shown to work well in extreme applied sciences. It predicts a linear, inverse relationship between entropy and volume when the temperature-to-pressure ratio is constant, which can explain the entropy-production behavior in shock-Hugoniots.
Standardization and quantitative analysis of Araucaria Heterophylla extract via an UPLC-MS/MS method and its formulation as an antibacterial phytonanoemulsion gel
Authors: Younis Nermin A. , Hemdan A. , Zafer Mai M. , Abd-Elsalam Wessam H. , Abouelatta Samar M.
Published: July 2022

Skin infections are among the bacterial infections that present significant therapeutic challenges due to antibiotic resistance. Recently, herbal products clutched a significant attention as safe replacements for other medications but their low aqueous solubility and poor bioavailability are considered major challenges which could be circumvented via formulation. As a species of genera Araucaria, Araucaria Heterophylla possesses pharmacological activities such as antioxidant and antibacterial actions, and this study aimed to standardize the extract of the plant against 4ʹʹʹmethoxyamentoflavone (as a main component of the extract) through a validated UPLC-MS/MS method and evaluate its antibacterial activity, which was followed by loading the standardized extract into a nanoemulsion to form a phytonanoemulsion (PNE), where the design analysis and optimization were performed through a simplex lattice design. The optimized PNE (PNE 3) was then loaded into HPMC/Pluronic F-127 gel (in ratio 1:4) to sustain the release of the active constituent. The heightened penetrability of PNE 3 gel was visualized via confocal laser scanning microscopy, and its prolonged effect was proved thru an in vivo study conducted on male Wistar rats. A histopathological study revealed the safety of the formulation when applied topically. Thus, PNE gel could be a potentially broad-spectrum antibacterial drug delivery system.
Evaluation of foliar application of selenium and flowering stages on selected properties of Iranian Borage as a medicinal plant
Authors: Hosseinzadeh Rostam Kalaei Mazaher , Abdossi Vahid , Danaee Elham
Published: July 2022

Many of the active constituents of drug or medicines were originally derived from medicinal plants. Iranian Borage are still being used in regular basis. Selenium (Se) is an essential mineral nutrient for animal and human growth. The aim of this research was to determine the effect of (2, 4, 8 and 16 mg L−1) of as sodium selenate (Na2SeO4) and as sodium selenite (Na2SeO3) on some important properties of Iranian Borage in factorial based on Randomized Complete Block Design via four steps: 2 true leaves stage, ten leaves, 2 weeks and 1 week before flowering. The traits were evaluated during flowering period. Results showed that the highest shoot fresh and dry weight and shoot length, total alkaloid, essential oil percentage were obtained by 4 mg L−1 sodium selenate at the end of flowering. In addition, 4 mg L−1 sodium selenate concentration significantly improved flower yield (diameter, number, weight). The plants were treated with 8 mg L−1 sodium selenate, the higher total phenols and flavonoids, antioxidant activity, soluble sugars, root and fresh weight was seen at end of flowering. When the plants were sprayed with 4 mg L−1 sodium selenite higher total chlorophyll was observed at full of flowering. 16 mg L−1 sodium selenite released the maximum Se acclimation in the petals. 20 composites were discovered containing ɑ-Pinene (23.61%) with sodium selenate in 4 mg L−1. Generally, selenium sources significantly improved morpho-physiological and phytochemical.