bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of RET inhibitor resistance in RET-driven lung and thyroid cancers
Authors: Rosen Ezra Y. , Won Helen H. , Zheng Youyun , Cocco Emiliano , Selcuklu Duygu , Gong Yixiao , Friedman Noah D. , de Bruijn Ino , Sumer Onur , Bielski Craig M. , Savin Casey , Bourque Caitlin , Falcon Christina , Clarke Nikeysha , Jing Xiaohong , Meng Fanli , Zimel Catherine , Shifman Sophie , Kittane Srushti , Wu Fan , Ladanyi Marc , Ebata Kevin , Kherani Jennifer , Brandhuber Barbara J. , Fagin James , Sherman Eric J. , Rekhtman Natasha , Berger Michael F. , Scaltriti Maurizio , Hyman David M. , Taylor Barry S. , Drilon Alexander
Published: March 2022

The efficacy of the highly selective RET inhibitor selpercatinib is now established in RET-driven cancers, and we sought to characterize the molecular determinants of response and resistance. We find that the pre-treatment genomic landscape does not shape the variability of treatment response except for rare instances of RAS-mediated primary resistance. By contrast, acquired selpercatinib resistance is driven by MAPK pathway reactivation by one of two distinct routes. In some patients, on- and off-target pathway reactivation via secondary RET solvent front mutations or MET amplifications are evident. In other patients, rare RET-wildtype tumor cell populations driven by an alternative mitogenic driver are selected for by treatment. Multiple distinct mechanisms are often observed in the same patient, suggesting polyclonal resistance may be common. Consequently, sequential RET-directed therapy may require combination treatment with inhibitors targeting alternative MAPK effectors, emphasizing the need for prospective characterization of selpercatinib-treated tumors at the time of monotherapy progression.
Characterization of protein unfolding by fast cross-linking mass spectrometry using di-ortho-phthalaldehyde cross-linkers
Authors: Wang Jian-Hua , Tang Yu-Liang , Gong Zhou , Jain Rohit , Xiao Fan , Zhou Yu , Tan Dan , Li Qiang , Huang Niu , Liu Shu-Qun , Ye Keqiong , Tang Chun , Dong Meng-Qiu , Lei Xiaoguang
Published: March 2022

Chemical cross-linking of proteins coupled with mass spectrometry is widely used in protein structural analysis. In this study we develop a class of non-hydrolyzable amine-selective di-ortho-phthalaldehyde (DOPA) cross-linkers, one of which is called DOPA2. Cross-linking of proteins with DOPA2 is 60–120 times faster than that with the N-hydroxysuccinimide ester cross-linker DSS. Compared with DSS cross-links, DOPA2 cross-links show better agreement with the crystal structures of tested proteins. More importantly, DOPA2 has unique advantages when working at low pH, low temperature, or in the presence of denaturants. Using staphylococcal nuclease, bovine serum albumin, and bovine pancreatic ribonuclease A, we demonstrate that DOPA2 cross-linking provides abundant spatial information about the conformations of progressively denatured forms of these proteins. Furthermore, DOPA2 cross-linking allows time-course analysis of protein conformational changes during denaturant-induced unfolding.
Hydrogen spillover assisted by oxygenate molecules over nonreducible oxides
Authors: Tan Mingwu , Yang Yanling , Yang Ying , Chen Jiali , Zhang Zhaoxia , Fu Gang , Lin Jingdong , Wan Shaolong , Wang Shuai , Wang Yong
Published: March 2022

Spontaneous migration of atomic hydrogen species from metal particles to the surface of their support, known as hydrogen spillover, has been claimed to play a major role in catalytic processes involving hydrogen. While this phenomenon is well established on reducible oxide supports, its realization on much more commonly used non-reducible oxides is still challenged. Here we present a general strategy to enable effective hydrogen spillover over non-reducible SiO2 with aid of gaseous organic molecules containing a carbonyl group. By using hierarchically-porous-SiO2-supported bimetallic Pt-Fe catalysts with Pt nanoparticles exclusively deposited into the micropores, we demonstrate that activated hydrogen species generated on the Pt sites within the micropores can be readily transported by these oxygenate molecules to Fe sites located in macropores, leading to significantly accelerated hydrodeoxygenation rates on the latter sites. This finding provides a molecule-assisted approach to the rational design and optimization of multifunctional heterogeneous catalysts, reminiscent of the role of molecular coenzymes in bio-catalysis.
A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats
Authors: Winans Shelby , Yu Hyun Jae , de los Santos Kenia , Wang Gary Z. , KewalRamani Vineet N. , Goff Stephen P.
Published: March 2022

Retroviruses utilize the viral integrase (IN) protein to integrate a DNA copy of their genome into host chromosomal DNA. HIV-1 integration sites are highly biased towards actively transcribed genes, likely mediated by binding of the IN protein to specific host factors, particularly LEDGF, located at these gene regions. We here report a substantial redirection of integration site distribution induced by a single point mutation in HIV-1 IN. Viruses carrying the K258R IN mutation exhibit a high frequency of integrations into centromeric alpha satellite repeat sequences, as assessed by deep sequencing, a more than 10-fold increase over wild-type. Quantitative PCR and in situ immunofluorescence assays confirm this bias of the K258R mutant virus for integration into centromeric DNA. Immunoprecipitation studies identify host factors binding to IN that may account for the observed bias for integration into centromeres. Centromeric integration events are known to be enriched in the latent reservoir of infected memory T cells, as well as in elite controllers who limit viral replication without intervention. The K258R point mutation in HIV-1 IN is also present in databases of latent proviruses found in patients, and may reflect an unappreciated aspect of the establishment of viral latency.
N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis
Authors: Han Hui , Yang Chunlong , Ma Jieyi , Zhang Shuishen , Zheng Siyi , Ling Rongsong , Sun Kaiyu , Guo Siyao , Huang Boxuan , Liang Yu , Wang Lu , Chen Shuang , Wang Zhaoyu , Wei Wei , Huang Ying , Peng Hao , Jiang Yi-Zhou , Choe Junho , Lin Shuibin
Published: March 2022

Mis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. Here we reveal that tRNA m7G methyltransferase complex proteins METTL1 and WDR4 are significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor ESCC prognosis. In addition, METTL1 and WDR4 promote ESCC progression via the tRNA m7G methyltransferase activity in vitro and in vivo. Mechanistically, METTL1 or WDR4 knockdown leads to decreased expression of m7G-modified tRNAs and reduces the translation of a subset of oncogenic transcripts enriched in RPTOR/ULK1/autophagy pathway. Furthermore, ESCC models using Mettl1 conditional knockout and knockin mice uncover the essential function of METTL1 in promoting ESCC tumorigenesis in vivo. Our study demonstrates the important oncogenic function of mis-regulated tRNA m7G modification in ESCC, and suggest that targeting METTL1 and its downstream signaling axis could be a promising therapeutic target for ESCC treatment.
S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy
Authors: Li Jianjie , Shu Xiaodong , Xu Jun , Su Sek Man , Chan Un In , Mo Lihua , Liu Jianlin , Zhang Xin , Adhav Ragini , Chen Qiang , Wang Yuqing , An Tingting , Zhang Xu , Lyu Xueying , Li Xiaoling , Lei Josh Haipeng , Miao Kai , Sun Heng , Xing Fuqiang , Zhang Aiping , Deng Chuxia , Xu Xiaoling
Published: March 2022

Immune checkpoint blockade (ICB) is a powerful approach for cancer therapy although good responses are only observed in a fraction of cancer patients. Breast cancers caused by deficiency of breast cancer-associated gene 1 (BRCA1) do not have an improved response to the treatment. To investigate this, here we analyze BRCA1 mutant mammary tissues and tumors derived from both BRCA1 mutant mouse models and human xenograft models to identify intrinsic determinants governing tumor progression and ICB responses. We show that BRCA1 deficiency activates S100A9-CXCL12 signaling for cancer progression and triggers the expansion and accumulation of myeloid-derived suppressor cells (MDSCs), creating a tumor-permissive microenvironment and rendering cancers insensitive to ICB. These oncogenic actions can be effectively suppressed by the combinatory treatment of inhibitors for S100A9-CXCL12 signaling with αPD-1 antibody. This study provides a selective strategy for effective immunotherapy in patients with elevated S100A9 and/or CXCL12 protein levels.
CrysXPP: An explainable property predictor for crystalline materials
Authors: Das Kishalay , Samanta Bidisha , Goyal Pawan , Lee Seung-Cheol , Bhattacharjee Satadeep , Ganguly Niloy
Published: March 2022

We present a deep-learning framework, CrysXPP, to allow rapid and accurate prediction of electronic, magnetic, and elastic properties of a wide range of materials. CrysXPP lowers the need for large property tagged datasets by intelligently designing an autoencoder, CrysAE. The important structural and chemical properties captured by CrysAE from a large amount of available crystal graphs data helped in achieving low prediction errors. Moreover, we design a feature selector that helps to interpret the model’s prediction. Most notably, when given a small amount of experimental data, CrysXPP is consistently able to outperform conventional DFT. A detailed ablation study establishes the importance of different design steps. We release the large pre-trained model CrysAE. We believe by fine-tuning the model with a small amount of property-tagged data, researchers can achieve superior performance on various applications with a restricted data source.
Antioxidant high-conductivity copper paste for low-cost flexible printed electronics
Authors: Hong Shuqing , Liu Chimin , Hao Shuqiang , Fu Wenxing , Peng Jian , Wu Binghui , Zheng Nanfeng
Published: March 2022

The flexible printed electronics (e.g., wearable devices, roll-up displays, heating circuits, radio frequency identification (RFID) tags) calls for high-conductivity and low-cost materials, particularly for copper pastes. It is still a big challenge to develop reliable copper pastes for both antioxidant and high-conductivity flexible printed films and lines. In this work, an antioxidant copper paste was achieved using copper microflakes with surface passivation by formate ions and thiols, with high conductivity of 13400 S cm−1 (the same order of magnitude of silver pastes, 1.8–2.5 × 104 S cm−1). The universal applications of as-prepared copper paste in flexible printed electronics (e.g., electromagnetic interference (EMI) shielding films, anti-fog films, and RFID tags) via screen printing and curing at 170 °C under ambient atmosphere were demonstrated. The as-printed electronics showed high performance in flexibility, stability, and reliability. This work shows the great potential of anti-oxidation copper pastes in low-cost flexible printed electronics for commercial usage.
Molecular ferroelectric/semiconductor interfacial memristors for artificial synapses
Authors: Cai Yichen , Zhang Jialong , Yan Mengge , Jiang Yizhou , Jawad Husnain , Tian Bobo , Wang Wenchong , Zhan Yiqiang , Qin Yajie , Xiong Shisheng , Cong Chunxiao , Qiu Zhi-Jun , Duan Chungang , Liu Ran , Hu Laigui
Published: March 2022

With the burgeoning developments in artificial intelligence, hardware implementation of artificial neural network is also gaining pace. In this pursuit, ferroelectric devices (i.e., tunneling junctions and transistors) with voltage thresholds were recently proposed as suitable candidates. However, their development is hindered by the inherent integration issues of inorganic ferroelectrics, as well as poor properties of conventional organic ferroelectrics. In contrast to the conventional ferroelectric synapses, here we demonstrated a two-terminal ferroelectric synaptic device using a molecular ferroelectric (MF)/semiconductor interface. The interfacial resistance can be tuned via the polarization-controlled blocking effect of the semiconductor, owing to the high ferroelectricity and field amplification effect of the MF. Typical synaptic features including spike timing-dependent plasticity are substantiated. The introduction of the semiconductor also enables the attributes of optoelectronic synapse and in-sensor computing with high image recognition accuracies. Such interfaces may pave the way for the hardware implementation of multifunctional neuromorphic devices.
The emerging postural instability phenotype in idiopathic Parkinson disease
Authors: Skidmore Frank M. , Monroe William S. , Hurt Christopher P. , Nicholas Anthony P. , Gerstenecker Adam , Anthony Thomas , Jololian Leon , Cutter Gary , Bashir Adil , Denny Thomas , Standaert David , Disbrow Elizabeth A.
Published: March 2022

Identification of individuals at high risk for rapid progression of motor and cognitive signs in Parkinson disease (PD) is clinically significant. Postural instability and gait dysfunction (PIGD) are associated with greater motor and cognitive deterioration. We examined the relationship between baseline clinical factors and the development of postural instability using 5-year longitudinal de-novo idiopathic data (n = 301) from the Parkinson’s Progressive Markers Initiative (PPMI). Logistic regression analysis revealed baseline features associated with future postural instability, and we designated this cohort the emerging postural instability (ePI) phenotype. We evaluated the resulting ePI phenotype rating scale validity in two held-out populations which showed a significantly higher risk of postural instability. Emerging PI phenotype was identified before onset of postural instability in 289 of 301 paired comparisons, with a median progression time of 972 days. Baseline cognitive performance was similar but declined more rapidly in ePI phenotype. We provide an ePI phenotype rating scale (ePIRS) for evaluation of individual risk at baseline for progression to postural instability.
Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson’s disease
Authors: Hauser Robert A. , Lytle Judy , Formella Andrea E. , Tanner Caroline M.
Published: March 2022

Maintaining consistent levodopa benefits while simultaneously controlling dyskinesia can be difficult. Recently, an amantadine delayed release/extended release (DR/ER) formulation (Gocovri®) indicated for dyskinesia received additional FDA approval as an adjunct to levodopa for the treatment of OFF episodes. We evaluated OFF time reductions with amantadine-DR/ER in a pooled analysis of two phase III amantadine-DR/ER trials (NCT02136914, NCT02274766) followed by a 2-year open-label extension trial (NCT02202551). OFF outcomes were analyzed for the mITT population, as well as stratified by baseline OFF time of ≥2.5 h/day or <2.5 h/day. At Week 12, mean placebo-subtracted treatment difference in OFF time was −1.00 [−1.57, −0.44] h in the mITT population (n = 196), −1.2 [−2.08, −0.32] h in the ≥2.5 h subgroup (n = 102) and −0.77 [−1.49, −0.06] in the <2.5 h subgroup (n = 94). Amantadine-DR/ER-treated participants showed reduced MDS-UPDRS Part IV motor fluctuation subscores by week 2 that were maintained below baseline to Week 100.
Reconstructing social mixing patterns via weighted contact matrices from online and representative surveys
Authors: Koltai Júlia , Vásárhelyi Orsolya , Röst Gergely , Karsai Márton
Published: March 2022

The unprecedented behavioural responses of societies have been evidently shaping the COVID-19 pandemic, yet it is a significant challenge to accurately monitor the continuously changing social mixing patterns in real-time. Contact matrices, usually stratified by age, summarise interaction motifs efficiently, but their collection relies on conventional representative survey techniques, which are expensive and slow to obtain. Here we report a data collection effort involving over $$2.3\%$$

2.3
%

of the Hungarian population to simultaneously record contact matrices through a longitudinal online and sequence of representative phone surveys. To correct non-representative biases characterising the online data, by using census data and the representative samples we develop a reconstruction method to provide a scalable, cheap, and flexible way to dynamically obtain closer-to-representative contact matrices. Our results demonstrate that although some conventional socio-demographic characters correlate significantly with the change of contact numbers, the strongest predictors can be collected only via surveys techniques and combined with census data for the best reconstruction performance. We demonstrate the potential of combined online-offline data collections to understand the changing behavioural responses determining the future evolution of the outbreak, and to inform epidemic models with crucial data.
Identification of hub genes and transcription factors in patients with rheumatoid arthritis complicated with atherosclerosis
Authors: Xiao Lu , Yang Zhou , Lin Shudian
Published: March 2022

The aim of this study was to explore the overlapping key genes, pathway networks and transcription factors (TFs) related to the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. The gene expression profiles of RA and atherosclerosis were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between RA and atherosclerosis were identified. The biological roles of common DEGs were explored through enrichment analysis. Hub genes were identified using protein–protein interaction networks. TFs were predicted using Transcriptional Regulatory Relationships Unraveled by Sentence Based Text Mining (TRRUST) database. The hub genes and TFs were validated with other datasets. The networks between TFs and hub genes were constructed by CytoScape software. A total of 131 DEGs (all upregulated) were identified. Functional enrichment analyses indicated that DEGs were mostly enriched in leukocyte migration, neutrophil activation, and phagocytosis. CytoScape demonstrated 12 hub genes and one gene cluster module. Four of the 12 hub genes (CSF1R, CD86, PTPRC, and CD53) were validated by other datasets. TRRUST predicted two TFs, including Spi-1 proto-oncogene (SPI1) and RUNX family transcription factor 1(RUNX1). The expression of RUNX1 was validated with another dataset. Our study explored the common pathogenesis of RA and atherosclerosis. These results may guide future experimental research and clinical transformation.
Response of tomatoes primed by mycorrhizal colonization to virulent and avirulent bacterial pathogens
Authors: Fujita Moeka , Kusajima Miyuki , Fukagawa Masatomo , Okumura Yasuko , Nakajima Masami , Akiyama Kohki , Asami Tadao , Yoneyama Koichi , Kato Hisaharu , Nakashita Hideo
Published: March 2022

Most plants interact with arbuscular mycorrhizal fungi, which enhance disease resistance in the host plant. Because the effects of resistance against bacterial pathogens are poorly understood, we investigated the effects of mycorrhizal colonization on virulent and avirulent pathogens using phytopathological and molecular biology techniques. Tomato plants colonized by Gigaspora margarita acquired resistance not only against the fungal pathogen, Botrytis cinerea, but also against a virulent bacterial pathogen, Pseudomonas syringae pv. tomato DC3000 (Pst). In G. margarita-colonized tomato, salicylic acid (SA)- and jasmonic acid (JA)-related defense genes were expressed more rapidly and strongly compared to those in the control plants when challenged by Pst, indicating that the plant immunity system was primed by mycorrhizal colonization. Gene expression analysis indicated that primed tomato plants responded to the avirulent pathogen, Pseudomonas syringae pv. oryzae, more rapidly and strongly compared to the control plant, where the effect on the JA-mediated signals was stronger than in the case with Pst. We found that the resistance induced by mycorrhizal colonization was effective against both fungal and bacterial pathogens including virulent and avirulent pathogens. Moreover, the activation of both SA- and JA-mediated signaling pathways can be enhanced in the primed plant by mycorrhizal colonization.
Emission from human skin in the sub THz frequency band
Authors: Betzalel Noa , Ben Ishai Paul , Puzenko Alexander , Feldman Yuri
Published: March 2022

Recently published Radiometric measurements of human subjects in the frequency range 480–700 GHz, demonstrate the emission of blackbody radiation from the body core, rather than the skin surface. We present a detailed electromagnetic simulation of the dermis and epidermis, taking into account the presence of the sweat duct. This complex structure can be considered as an electromagnetic bio-metamaterial, whereby the layered structure, along with the topology of the sweat duct, reveals a complex interference pattern in the skin. The model is capable of accurately representing the skin greyness factor as a function of frequency and this is confirmed by radiometry of living human skin.
Residual characteristics and safety assessment of the insecticides spiromesifen and chromafenozide in lettuce and perilla
Authors: Sardar Syed Wasim , Byeon Geon Doo , Choi Jeong Yoon , Ham Hun Ju , Ishag Abd Elaziz Sulieman Ahmed , Hur Jang Hyun
Published: March 2022

This study was performed to investigate the residual characteristics, safety assessment, and pre-harvest interval (PHI) of spiromesifen and chromafenozide in lettuce (Latuca sativa L.) and perilla (Perilla frutescens (L.) Britton) leaves. Samples were harvested periodically, extracted using QuEChERS method, and analyzed by LC-MS/MS. Average recoveries of spiromesifen and its metabolite BSN2060-enol and chromafenozide were ranged from 80.6 to 107.9%, with relative standard deviation < 10%. Spiromesifen and cromafenozide initial residues in lettuce were dissipated to 81.45 and 95.52% after 7 days, with half-lives of 2.89 and 1.69 days respectively. Values in perilla leaves were 76.68 and 61.27% after the same period, with half-lives of 4.25 and 6.30 days, respectively. Risk assessment results showed that %ADI (acceptable daily intake) of spiromesifen and chromafenozide was 6.83 and 0.56, in lettuce and 4.60 and 0.25% in perilla leaves, respectively. Theoretical maximum daily intakes of spiromesifen and chromafenozide were 67.49 and 3.43%, respectively, indicating that residues of both compounds pose no considerable health risks to consumers. This study provides data for setting maximum residue limits and PHIs for the safe use of spiromesifen and chromafenozide in lettuce and perilla.
An intuitive protocol for polarization-entanglement restoral of quantum dot photon sources with non-vanishing fine-structure splitting
Authors: Varo Simone , Juska Gediminas , Pelucchi Emanuele
Published: March 2022

Generation of polarization-entangled photons from quantum dots via the biexciton-exciton recombination cascade is complicated by the presence of an energy splitting between the intermediate excitonic levels, which severely degrades the quality of the entangled photon source. In this paper we present a novel, conceptually simple and straightforward proposal for restoring the entanglement of said source by applying a cascade of time-dependent operations on the emitted photons. This is in striking contrast with the techniques usually employed, that act on the quantum emitter itself in order to remove the fine structure splitting at its root. The feasibility of the implementation with current technology is discussed, and the robustness of the proposed compensation scheme with respect to imperfections of the experimental apparatus is evaluated via a series of Monte Carlo simulations.
Admission electrolyte and osmotic pressure levels are associated with the incidence of contrast-associated acute kidney injury
Authors: Lv Qingbo , Li Duanbin , Wang Yao , Yu Pengcheng , Zhao Liding , Chen Songzan , Wang Min , Fu Guosheng , Zhang Wenbin
Published: March 2022

This retrospective study aimed to explore the relationships between electrolytes and osmotic pressure homeostasis with contrast-associated acute kidney injury (CA-AKI) risk in patients with percutaneous coronary intervention or coronary angiography. We totally enrolled 4386 hospitalized patients, who were categorized into five groups based on the predetermined cutoff values of electrolytes and osmotic pressure. CA-AKI was defined as an increase in serum creatine by 0.5 mg/dL (44.2 mol/L) or a 25% increase of the highest level post-operation compared to baseline. Multivariable logistic analysis was used to examine the association of CA-AKI incidence with electrolytes and osmotic pressure levels. Piecewise linear regression models and restricted cubic spline analysis were further utilized to determine the nonlinear relationship. The results showed U-shaped relationships between sodium, chloride, magnesium, and osmotic pressure levels and CA-AKI incidence. The lowest incidence was observed in the categories of 139–141.9 mmol/L, 107.0–109.9 mmol/L, 0.91–1.07 mmol/L, and 290.0–299.9 mOsm/kg, respectively. J-shaped associations were observed for potassium and phosphate levels and CA-AKI incidence, with the lowest incidence in the categories of 3.50–4.09 mmol/L and 0.96–1.28 mmol/L, respectively. A negative correlation was observed between calcium level and CA-AKI incidence, with the lowest CA-AKI risk in the category of ≥ 2.58 mmol/L. In conclusion, abnormally higher or lower sodium, chloride, magnesium, phosphate, and osmotic pressure levels on admission were associated with increased risks of CA-AKI. While for potassium and calcium, the status of hyperkalemia and hypocalcemia on admission showed more susceptibility for CA-AKI.
Transcriptome analysis of the bivalve Placuna placenta mantle reveals potential biomineralization-related genes
Authors: Song Ningjing , Li Jiangfeng , Li Baosheng , Pan Ercai , Ma Yurong
Published: March 2022

The shells of window pane oyster Placuna placenta are very thin and exhibit excellent optical transparency and mechanical robustness. However, little is known about the biomineralization-related proteins of the shells of P. placenta. In this work, we report the comprehensive transcriptome of the mantle tissue of P. placenta for the first time. The unigenes of the mantle tissue of P. placenta were annotated by using the public databases such as nr, GO, KOG, KEGG, and Pfam. 24,343 unigenes were annotated according to Pfam database, accounting for 21.48% of the total unigenes. We find that half of the annotated unigenes of the mantle tissue of P. placenta are consistent to the annotated unigenes from pacific oyster Crassostrea gigas according to nr database. The unigene sequence analysis from the mantle tissue of P. placenta indicates that 465,392 potential single nucleotide polymorphisms (SNPs) and 62,103 potential indel markers were identified from 60,371 unigenes. 178 unigenes of the mantle tissue of P. placenta are found to be homologous to those reported proteins related to the biomineralization process of molluscan shells, while 18 of them are highly expressed unigenes in the mantle tissue. It is proposed that four unigenes with the highest expression levels in the mantle tissue are very often related to the biomineralization process, while another three unigenes are potentially related to the biomineralization process according to the Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis. In summary, the transcriptome analysis of the mantle tissue of P. Placenta shows the potential biomineralization-related proteins and this work may shed light for the shell formation mechanism of bivalves.
T1 reduction rate with Gd-EOB-DTPA determines liver function on both 1.5 T and 3 T MRI
Authors: Obmann Verena Carola , Catucci Damiano , Berzigotti Annalisa , Gräni Christoph , Ebner Lukas , Heverhagen Johannes Thomas , Christe Andreas , Huber Adrian Thomas
Published: March 2022

Magnetic resonance T1 mapping before and after Gd-EOB-DTPA administration allows quantification of the T1 reduction rate as a non-invasive surrogate marker of liver function. A major limitation of T1 relaxation time measurement is its dependency on MRI field strengths. Since T1 reduction rate is calculated as the relative shortening of T1 relaxation time before and after contrast administration, we hypothesized that the T1 reduction rate is comparable between 1.5 and 3 T. We thus compared liver T1 relaxation times between 1.5 and 3 T in a total of 243 consecutive patients (124, 1.5 T and 119, 3 T) between 09/2018 and 07/2019. T1 reduction rates were compared between patients with no cirrhosis and patients with cirrhosis Child–Pugh A-C. There was no significant difference of T1 reduction rate between 1.5 and 3 T in any patient group (p-value 0.126–0.861). On both 1.5 T and 3 T, T1 reduction rate allowed to differentiate between patients with no cirrhosis and patients with liver cirrhosis Child A-C (p < 0.001). T1 reduction rate showed a good performance to predict liver cirrhosis Child A (AUC = 0.83, p < 0.001), Child B (AUC = 0.83, p < 0.001) and Child C (AUC = 0.92, p < 0.001). In conclusion, T1 reduction rate allows to determine liver function on Gd-EOB-DTPA MRI with comparable values on 1.5 T and 3 T.
Attributing changes in food insecurity to a changing climate
Authors: Dasgupta Shouro , Robinson Elizabeth J. Z.
Published: March 2022

It is generally accepted that climate change is having a negative impact on food security. However, most of the literature variously focuses on the complex and many mechanisms linking climate stressors; the links with food production or productivity rather than food security; and future rather than current effects. In contrast, we investigate the extent to which current changes in food insecurity can be plausibly attributed to climate change. We combine food insecurity data for 83 countries from the FAO food insecurity experience scale (FIES) with reanalysed climate data from ERA5-Land, and use a panel data regression with time-varying coefficients. This framework allows us to estimate whether the relationship between food insecurity and temperature anomaly is changing over time. We also control for Human Development Index, and drought measured by six-month Standardized Precipitation Index. Our empirical findings suggest that for every 1 $$^{\circ }\hbox {C}$$∘Cof temperature anomaly, severe global food insecurity has increased by 1.4% (95% CI 1.3–1.47) in 2014 but by 1.64% (95% CI 1.6–1.65) in 2019. This impact is higher in the case of moderate to severe food insecurity, with a 1 $$^{\circ }\hbox {C}$$∘Cincrease in temperature anomaly resulting in a 1.58% (95% CI 1.48–1.68) increase in 2014 but a 2.14% (95% CI 2.08–2.20) increase in 2019. Thus, the results show that the temperature anomaly has not only increased the probability of food insecurity, but the magnitude of this impact has increased over time. Our counterfactual analysis suggests that climate change has been responsible for reversing some of the improvements in food security that would otherwise have been realised, with the highest impact in Africa. Our analysis both provides more evidence of the costs of climate change, and as such the benefits of mitigation, and also highlights the importance of targeted and efficient policies to reduce food insecurity. These policies are likely to need to take into account local contexts, and might include efforts to increase crop yields, targeted safety nets, and behavioural programs to promote household resilience.
Advances in multiscale image processing and its effects on image quality in skeletal radiography
Authors: Notohamiprodjo Susan , Roeper K. M. , Mueck F. G. , Maxien D. , Wanninger F. , Hoberg B. , Verstreepen L. , Treitl K. M. , Fischer F. , Peschel O. , Wirth S.
Published: March 2022

Multi-frequency processing (MFP) leads to enhanced image quality (IQ) of radiographs. This study is to determine the effect of third generation MFP (M3) on IQ in comparison to standard second-generation MFP (M2). 20 cadavers were examined and post-processing of radiographs was performed with both M2 and M3. Three readers blinded to the MFP used for each image independently compared corresponding image pairs according to overall IQ and depiction of bony structures and soft tissue (+ 2: notably better > 0: equal > − 2: notably worse). A significant deviation of the median grade from grade 0 (equal) (p < 0.01) for each evaluator A, B and C speaks against an equal image quality of M2- and M3-images. M3-images were categorized with better grades (+ 1, + 2) in 87.7% for overall image quality, in 90.4% for soft tissue and 81.8% for bony structures. M3 images showed significant higher averaged SNR and CNR for all investigated lower extremities than that of M2 images (0.031 < p < 0.049). The newest generation of MFP leads to significantly better depiction of anatomical structures and overall image quality than in images processed with the preceding generation of MFP. This provides increased diagnostic accuracy and further decreased radiation exposure.
Reduced-cost two-level surrogate antenna modeling using domain confinement and response features
Authors: Pietrenko-Dabrowska Anna , Koziel Slawomir , Ullah Ubaid
Published: March 2022

Electromagnetic (EM) simulation tools have become indispensable in the design of contemporary antennas. Still, the major setback of EM-driven design is the associated computational overhead. This is because a single full-wave simulation may take from dozens of seconds up to several hours, thus, the cost of solving design tasks that involve multiple EM analyses may turn unmanageable. This is where faster system representations (surrogates) come into play. Replacing expensive EM-based evaluations by cheap yet accurate metamodels seems to be an attractive solution. Still, in antenna design, application of surrogate models is hindered by the curse of dimensionality. A practical workaround has been offered by the recently reported reference-design-free constrained modeling techniques that restrict the metamodel domain to the parameter space region encompassing high-quality designs. Therein, the domain is established using only a handful of EM-simulations. This paper proposes a novel modeling technique, which incorporates the response feature technology into the constrained modeling framework. Our methodology allows for rendering accurate surrogates using exceptionally small training data sets, at the expense of reducing the generality of the modeling procedure to antennas that exhibit consistent shape of input characteristics. The proposed technique can be employed in other fields that employ costly simulation models (e.g., mechanical or aerospace engineering).
l-Carnitine reduces reactive oxygen species/endoplasmic reticulum stress and maintains mitochondrial function during autophagy-mediated cell apoptosis in perfluorooctanesulfonate-treated renal tubular cells
Authors: Lee Yuan-Chii Gladys , Chou Hsiu-Chu , Chen Yen-Ting , Tung Szu-Yu , Ko Tsui-Ling , Buyandelger Batsaikhan , Wen Li-Li , Juan Shu-Hui
Published: March 2022

We previously reported that perfluorooctanesulfonate (PFOS) causes autophagy-induced apoptosis in renal tubular cells (RTCs) through a mechanism dependent on reactive oxygen species (ROS)/extracellular signal-regulated kinase. This study extended our findings and determined the therapeutic potency of l-Carnitine in PFOS-treated RTCs. l-Carnitine (10 mM) reversed the effects of PFOS (100 µM) on autophagy induction and impaired autophagy flux. Furthermore, it downregulated the protein level of p47Phox, which is partly related to PFOS-induced increased cytosolic ROS in RTCs. Moreover, l-Carnitine reduced ROS production in mitochondria and restored PFOS-impeded mitochondrial function, leading to sustained normal adenosine triphosphate synthesis and oxygen consumption and reduced proton leakage in a Seahorse XF stress test. The increased inositol-requiring enzyme 1α expression by PFOS, which indicated endoplasmic reticulum (ER) stress activation, was associated with PFOS-mediated autophagy activation that could be attenuated through 4-phenylbutyrate (5 mM, an ER stress inhibitor) and l-Carnitine pretreatment. Therefore, by reducing the level of IRE1α, l-Carnitine reduced the levels of Beclin and LC3BII, consequently reducing the level of apoptotic biomarkers including Bax and cleaving PARP and caspase 3. Collectively, these results indicate that through the elimination of oxidative stress, extracellular signal–regulated kinase activation, and ER stress, l-Carnitine reduced cell autophagy/apoptosis and concomitantly increased cell viability in RTCs. This study clarified the potential mechanism of PFOS-mediated RTC apoptosis and provided a new strategy for using l-Carnitine to prevent and treat PFOS-induced RTC apoptosis.
New proposed ITER divertor design using carbon insert on tungsten to mitigate ELMs and secondary radiation effects on nearby components
Authors: Sizyuk V. , Hassanein A.
Published: March 2022

Building a successful device for the magnetic fusion energy production is a great challenge. ITER is an international project of the tokamak based magnetic fusion design being developed for the demonstration of the feasibility of thermonuclear technologies for future realization of successful commercial fusion energy. A key obstacle to a successful magnetic fusion energy production is however, the performance during abnormal events including plasma disruptions and edge-localized modes (ELMs). A credible reactor design must tolerate at least a few of these transient events without serious consequences such as melting of the structure. This paper investigates and compares the performance of the current ITER tokamak design during two types of transient events, i.e., ELMs occurring at normal operation and disruptions during abnormal operation. We simulated the divertor components response using our integrated 3D HEIGHTS package. The simulations include self-consistent modeling of the interaction of the released core plasma particles with the initial solid divertor material, energy deposition processes, vaporization of divertor material, secondary plasma formation and MHD evolution, incident core particles collisions and scattering from this dense secondary plasma, photon radiation of secondary plasma, and the resulting heat loads on nearby components. Our simulations showed that using a small carbon insert around the strike point can significantly reduce the overall expected damage on the tungsten dome structure, reflector plates, and prevent tungsten vaporization and its potential core plasma contamination.
Using deep learning to predict human decisions and using cognitive models to explain deep learning models
Authors: Fintz Matan , Osadchy Margarita , Hertz Uri
Published: March 2022

Deep neural networks (DNNs) models have the potential to provide new insights in the study of cognitive processes, such as human decision making, due to their high capacity and data-driven design. While these models may be able to go beyond theory-driven models in predicting human behaviour, their opaque nature limits their ability to explain how an operation is carried out, undermining their usefulness as a scientific tool. Here we suggest the use of a DNN model as an exploratory tool to identify predictable and consistent human behaviour, and using explicit, theory-driven models, to characterise the high-capacity model. To demonstrate our approach, we trained an exploratory DNN model to predict human decisions in a four-armed bandit task. We found that this model was more accurate than two explicit models, a reward-oriented model geared towards choosing the most rewarding option, and a reward-oblivious model that was trained to predict human decisions without information about rewards. Using experimental simulations, we were able to characterise the exploratory model using the explicit models. We found that the exploratory model converged with the reward-oriented model’s predictions when one option was clearly better than the others, but that it predicted pattern-based explorations akin to the reward-oblivious model’s predictions. These results suggest that predictable decision patterns that are not solely reward-oriented may contribute to human decisions. Importantly, we demonstrate how theory-driven cognitive models can be used to characterise the operation of DNNs, making DNNs a useful explanatory tool in scientific investigation.
Symmetry-dependent exciton-exciton interaction and intervalley biexciton in monolayer transition metal dichalcogenides
Authors: Cam Hoang Ngoc , Phuc Nguyen Thanh , Osipov Vladimir A.
Published: March 2022

The multivalley band structure of monolayer transition metal dichalcogenides (TMDs) gives rise to intravalley and intervalley excitons. Much knowledge of these excitons has been gained, but fundamental questions remain, such as how to describe them all in a unified picture with their correlations, how are those from different valleys coupled to form the intervalley biexciton? To address the issues, we derive an exciton Hamiltonian from interpair correlations between the constituent carriers-fermions of two excitons. Identifying excitons by irreducible representations of their point symmetry group, we find their pairwise interaction depending on interacting excitons’ symmetry. It is generally repulsive, except for the case excitons from different valleys, which attract each other to form the intervalley biexciton. We establish a semianalytical relationship between the biexciton binding energy with exciton mass and dielectric characteristics of the material and surroundings. Overall, by providing insight into the nature of diverse excitons and their correlations, our theoretical model captures the exciton interaction properties permitting an inclusive description of the structure and energy features of the intervalley biexciton in monolayer TMDs.
ZIKV can infect human term placentas in the absence of maternal factors
Authors: Villazana-Kretzer Diana L. , Wuertz Kathryn McGuckin , Newhouse Daniel , Damicis Jennifer R. , Dornisch Elisabeth M. , Voss Kathleen M. , Muruato Antonio E. , Paymaster Jennifer A. , Schmiedecke Stacey S. , Edwards Sarah M. , Napolitano Peter G. , Tisoncik-Go Jennifer , Ieronimakis Nicholas , Gale Michael
Published: March 2022

Zika virus infection can result in devastating pregnancy outcomes when it crosses the placental barrier. For human pregnancies, the mechanisms of vertical transmission remain enigmatic. Utilizing a human placenta-cotyledon perfusion model, we examined Zika virus exposure in the absence of maternal factors. To distinguish responses related to viral infectionvs. recognition, we evaluated cotyledons perfused with either active or inactivated Zika virus. Active Zika virus exposure resulted in infection, cell death and syncytium injury. Pathology corresponded with transcriptional changes related to inflammation and innate immunity. Inactive Zika virus exposure also led to syncytium injury and related changes in gene expression but not cell death. Our observations reveal pathologies and innate immune responses that are dependent on infection or virus placenta interactions independent of productive infection. Importantly, our findings indicate that Zika virus can infect and compromise placentas in the absence of maternal humoral factors that may be protective.
Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice
Authors: Ordonez Alvaro A. , Bullen C. Korin , Villabona-Rueda Andres F. , Thompson Elizabeth A. , Turner Mitchell L. , Merino Vanessa F. , Yan Yu , Kim John , Davis Stephanie L. , Komm Oliver , Powell Jonathan D. , D’Alessio Franco R. , Yolken Robert H. , Jain Sanjay K. , Jones-Brando Lorraine
Published: March 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are limited therapeutic options for the prevention and treatment of SARS-CoV-2 infections. We evaluated the antiviral activity of sulforaphane (SFN), the principal biologically active phytochemical derived from glucoraphanin, the naturally occurring precursor present in high concentrations in cruciferous vegetables. SFN inhibited in vitro replication of six strains of SARS-CoV-2, including Delta and Omicron, as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN should be explored as a potential agent for the prevention or treatment of coronavirus infections.
A global microbiome survey of vineyard soils highlights the microbial dimension of viticultural terroirs
Authors: Gobbi Alex , Acedo Alberto , Imam Nabeel , Santini Rui G. , Ortiz-Álvarez Rüdiger , Ellegaard-Jensen Lea , Belda Ignacio , Hansen Lars H.
Published: March 2022

The microbial biodiversity found in different vitivinicultural regions is an important determinant of wine terroir. It should be studied and preserved, although it may, in the future, be subjected to manipulation by precision agriculture and oenology. Here, we conducted a global survey of vineyards’ soil microbial communities. We analysed soil samples from 200 vineyards on four continents to establish the basis for the development of a vineyard soil microbiome’s map, representing microbial biogeographical patterns on a global scale. This study describes vineyard microbial communities worldwide and establishes links between vineyard locations and microbial biodiversity on different scales: between continents, countries, and between different regions within the same country. Climate data correlates with fungal alpha diversity but not with prokaryotes alpha diversity, while spatial distance, on a global and national scale, is the main variable explaining beta-diversity in fungal and prokaryotes communities. Proteobacteria, Actinobacteria and Acidobacteria phyla, and Archaea genus Nitrososphaera dominate prokaryotic communities in soil samples while the overall fungal community is dominated by the genera Solicoccozyma, Mortierella and Alternaria. Finally, we used microbiome data to develop a predictive model based on random forest analyses to discriminate between microbial patterns and to predict the geographical source of the samples with reasonable precision.
Mineral-enriched biochar delivers enhanced nutrient recovery and carbon dioxide removal
Authors: Buss Wolfram , Wurzer Christian , Manning David A. C. , Rohling Eelco J. , Borevitz Justin , Mašek Ondřej
Published: March 2022

Biochar production via biomass pyrolysis with subsequent burial in soils provides a carbon dioxide removal technology that is ready for implementation, yet uptake requires acceleration; notably, through generation of cost reductions and co-benefits. Here we find that biomass enrichment (doping) with refined minerals, mineral by-products, or ground rocks reduces carbon loss during pyrolysis, lowering carbon dioxide removal costs by 17% to US$ 80–150 t−1 CO2, with 30% savings feasible at higher biomass costs. As a co-benefit, all three additives increase plant-available nutrient levels. Doping with potassium-bearing minerals can increase both potassium and phosphorus release. Mineral doping in biochar production therefore offers carbon dioxide removal at lower costs, while alleviating global phosphorus and potassium shortages. This makes it unique among carbon dioxide removal technologies.