bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsupervised content-preserving transformation for optical microscopy
Authors: Li Xinyang , Zhang Guoxun , Qiao Hui , Bao Feng , Deng Yue , Wu Jiamin , He Yangfan , Yun Jingping , Lin Xing , Xie Hao , Wang Haoqian , Dai Qionghai
Published: March 2021

The development of deep learning and open access to a substantial collection of imaging data together provide a potential solution for computational image transformation, which is gradually changing the landscape of optical imaging and biomedical research. However, current implementations of deep learning usually operate in a supervised manner, and their reliance on laborious and error-prone data annotation procedures remains a barrier to more general applicability. Here, we propose an unsupervised image transformation to facilitate the utilization of deep learning for optical microscopy, even in some cases in which supervised models cannot be applied. Through the introduction of a saliency constraint, the unsupervised model, named Unsupervised content-preserving Transformation for Optical Microscopy (UTOM), can learn the mapping between two image domains without requiring paired training data while avoiding distortions of the image content. UTOM shows promising performance in a wide range of biomedical image transformation tasks, including in silico histological staining, fluorescence image restoration, and virtual fluorescence labeling. Quantitative evaluations reveal that UTOM achieves stable and high-fidelity image transformations across different imaging conditions and modalities. We anticipate that our framework will encourage a paradigm shift in training neural networks and enable more applications of artificial intelligence in biomedical imaging.
Towards next generation white LEDs: optics-electronics synergistic effect in a single-layer heterophase halide perovskite
Authors: Rogach Andrey L.
Published: March 2021

A novel concept of the heterophase optics-electronics synergistic effect has been demonstrated in a single-layer α/δ-heterophase perovskite CsPbI3 in order to realize white LEDs featuring only one broadband emissive layer.
Genomic network analysis of environmental and livestock F-type plasmid populations
Authors: Matlock William , Chau Kevin K , AbuOun Manal , Stubberfield Emma , Barker Leanne , Kavanagh James , Pickford Hayleah , Gilson Daniel , Smith Richard P , Gweon H Soon , Hoosdally Sarah J , Swann Jeremy , Sebra Robert , Bailey Mark J , Peto Timothy E A , Crook Derrick W , Anjum Muna F , Read Daniel S , Walker A Sarah , Stoesser Nicole , Shaw Liam P ,   REHAB consortium, AbuOun Manal , Anjum Muna F , Bailey Mark J , Brett H , Bowes Mike J , Chau Kevin K , Crook Derrick W , de Maio Nicola , Duggett Nicholas , Wilson Daniel J , Gilson Daniel , Gweon H Soon , Hubbard Alasdair , Hoosdally Sarah J , Matlock William , Kavanagh James , Jones Hannah , Peto Timothy E A , Read Daniel S , Sebra Robert , Shaw Liam P , Sheppard Anna E , Smith Richard P , Stubberfield Emma , Stoesser Nicole , Swann Jeremy , Walker A Sarah , Woodford Neil
Published: March 2021

F-type plasmids are diverse and of great clinical significance, often carrying genes conferring antimicrobial resistance (AMR) such as extended-spectrum β-lactamases, particularly in Enterobacterales. Organising this plasmid diversity is challenging, and current knowledge is largely based on plasmids from clinical settings. Here, we present a network community analysis of a large survey of F-type plasmids from environmental (influent, effluent and upstream/downstream waterways surrounding wastewater treatment works) and livestock settings. We use a tractable and scalable methodology to examine the relationship between plasmid metadata and network communities. This reveals how niche (sampling compartment and host genera) partition and shape plasmid diversity. We also perform pangenome-style analyses on network communities. We show that such communities define unique combinations of core genes, with limited overlap. Building plasmid phylogenies based on alignments of these core genes, we demonstrate that plasmid accessory function is closely linked to core gene content. Taken together, our results suggest that stable F-type plasmid backbone structures can persist in environmental settings while allowing dramatic variation in accessory gene content that may be linked to niche adaptation. The association of F-type plasmids with AMR may reflect their suitability for rapid niche adaptation.
Fine-scale metabolic discontinuity in a stratified prokaryote microbiome of a Red Sea deep halocline
Authors: Michoud Grégoire , Ngugi David Kamanda , Barozzi Alan , Merlino Giuseppe , Calleja Maria Ll , Delgado-Huertas Antonio , Morán Xosé Anxelu G , Daffonchio Daniele
Published: March 2021

Deep-sea hypersaline anoxic basins are polyextreme environments in the ocean’s interior characterized by the high density of brines that prevents mixing with the overlaying seawater, generating sharp chemoclines and redoxclines up to tens of meters thick that host a high concentration of microbial communities. Yet, a fundamental understanding of how such pycnoclines shape microbial life and the associated biogeochemical processes at a fine scale, remains elusive. Here, we applied high-precision sampling of the brine–seawater transition interface in the Suakin Deep, located at 2770 m in the central Red Sea, to reveal previously undocumented fine-scale community structuring and succession of metabolic groups along a salinity gradient only 1 m thick. Metagenomic profiling at a 10-cm-scale resolution highlighted spatial organization of key metabolic pathways and corresponding microbial functional units, emphasizing the prominent role and significance of salinity and oxygen in shaping their ecology. Nitrogen cycling processes are especially affected by the redoxcline with ammonia oxidation processes being taxa and layers specific, highlighting also the presence of novel microorganisms, such as novel Thaumarchaeota and anammox, adapted to the changing conditions of the chemocline. The findings render the transition zone as a critical niche for nitrogen cycling, with complementary metabolic networks, in turn underscoring the biogeochemical complexity of deep-sea brines.
Antihypertensive treatment guided by genetics: PEARL-HT, the randomized proof-of-concept trial comparing rostafuroxin with losartan
Authors: Citterio Lorena , Bianchi Giuseppe , Scioli Giuseppe A. , Glorioso Nicola , Bigazzi Roberto , Cusi Daniele , Staessen Jan A. , Cavuto Silvio , Ferrandi Mara , Lanzani Chiara , Li Xiaoyi , Lau Lit-Fui , Chiang Chern-En , Wang Tzung-Dau , Wang Kang-Ling , Ferrari Patrizia , Manunta Paolo
Published: March 2021

We compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension. Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10–11 M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in office systolic blood pressure (OSBP) after 2-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (LSS and HSD3B1), EO transport (MDR1/ABCB1), adducin (ADD1 and ADD3); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6–19.0), P = 0.038 and 13.4 (25.4–2.5), P = 0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former (P = 0.038); this difference was abolished by rostafuroxin at 10–11 M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that genetics may guide drug treatment for primary hypertension in Caucasians.
sRNAanno—a database repository of uniformly annotated small RNAs in plants
Authors: Chen Chengjie , Li Jiawei , Feng Junting , Liu Bo , Feng Lei , Yu Xiaoling , Li Guanliang , Zhai Jixian , Meyers Blake C. , Xia Rui
Published: March 2021

Small RNAs (sRNAs) are essential regulatory molecules, and there are three major sRNA classes in plants: microRNAs (miRNAs), phased small interfering RNAs (phased siRNAs or phasiRNAs), and heterochromatic siRNAs (hc-siRNAs). Excluding miRNAs, the other two classes are not well annotated or available in public databases for most sequenced plant genomes. We performed a comprehensive sRNA annotation of 143 plant species that have fully sequenced genomes and next-generation sequencing sRNA data publicly available. The results are available via an online repository called sRNAanno (www.plantsRNAs.org). Compared with other public plant sRNA databases, we obtained was much more miRNA annotations, which are more complete and reliable because of the consistent and highly stringent criteria used in our miRNA annotations. sRNAanno also provides free access to genomic information for >22,721 PHAS loci and >22 million hc-siRNA loci annotated from these 143 plant species. Both miRNA and PHAS loci can be easily browsed to view their main features, and a collection of archetypal trans-acting siRNA 3 (TAS3) genes were annotated separately for quick access. To facilitate the ease of sRNA annotation, sRNAanno provides free service for sRNA annotations to the community. In summary, the sRNAanno database is a great resource to facilitate genomic and genetic research on plant small RNAs.
Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy
Authors: Jiang Cheng-Tao , Chen Kai-Ge , Liu An , Huang Hua , Fan Ya-Nan , Zhao Dong-Kun , Ye Qian-Ni , Zhang Hou-Bing , Xu Cong-Fei , Shen Song , Xiong Meng-Hua , Du Jin-Zhi , Yang Xian-Zhu , Wang Jun
Published: March 2021

Modulating effector immune cells via monoclonal antibodies (mAbs) and facilitating the co-engagement of T cells and tumor cells via chimeric antigen receptor- T cells or bispecific T cell-engaging antibodies are two typical cancer immunotherapy approaches. We speculated that immobilizing two types of mAbs against effector cells and tumor cells on a single nanoparticle could integrate the functions of these two approaches, as the engineered formulation (immunomodulating nano-adaptor, imNA) could potentially associate with both cells and bridge them together like an ‘adaptor’ while maintaining the immunomodulatory properties of the parental mAbs. However, existing mAbs-immobilization strategies mainly rely on a chemical reaction, a process that is rough and difficult to control. Here, we build up a versatile antibody immobilization platform by conjugating anti-IgG (Fc specific) antibody (αFc) onto the nanoparticle surface (αFc-NP), and confirm that αFc-NP could conveniently and efficiently immobilize two types of mAbs through Fc-specific noncovalent interactions to form imNAs. Finally, we validate the superiority of imNAs over the mixture of parental mAbs in T cell-, natural killer cell- and macrophage-mediated antitumor immune responses in multiple murine tumor models.
Single-molecule long-read sequencing reveals a conserved intact long RNA profile in sperm
Authors: Sun Yu H. , Wang Anqi , Song Chi , Shankar Goutham , Srivastava Rajesh K. , Au Kin Fai , Li Xin Zhiguo
Published: March 2021

Sperm contributes diverse RNAs to the zygote. While sperm small RNAs have been shown to impact offspring phenotypes, our knowledge of the sperm transcriptome, especially the composition of long RNAs, has been limited by the lack of sensitive, high-throughput experimental techniques that can distinguish intact RNAs from fragmented RNAs, known to abound in sperm. Here, we integrate single-molecule long-read sequencing with short-read sequencing to detect sperm intact RNAs (spiRNAs). We identify 3440 spiRNA species in mice and 4100 in humans. The spiRNA profile consists of both mRNAs and long non-coding RNAs, is evolutionarily conserved between mice and humans, and displays an enrichment in mRNAs encoding for ribosome. In sum, we characterize the landscape of intact long RNAs in sperm, paving the way for future studies on their biogenesis and functions. Our experimental and bioinformatics approaches can be applied to other tissues and organisms to detect intact transcripts.
Rational design of isostructural 2D porphyrin-based covalent organic frameworks for tunable photocatalytic hydrogen evolution
Authors: Chen Rufan , Wang Yang , Ma Yuan , Mal Arindam , Gao Xiao-Ya , Gao Lei , Qiao Lijie , Li Xu-Bing , Wu Li-Zhu , Wang Cheng
Published: March 2021

Covalent organic frameworks have recently gained increasing attention in photocatalytic hydrogen generation from water. However, their structure-property-activity relationship, which should be beneficial for the structural design, is still far-away explored. Herein, we report the designed synthesis of four isostructural porphyrinic two-dimensional covalent organic frameworks (MPor-DETH-COF, M = H2, Co, Ni, Zn) and their photocatalytic activity in hydrogen generation. Our results clearly show that all four covalent organic frameworks adopt AA stacking structures, with high crystallinity and large surface area. Interestingly, the incorporation of different transition metals into the porphyrin rings can rationally tune the photocatalytic hydrogen evolution rate of corresponding covalent organic frameworks, with the order of CoPor-DETH-COF < H2Por-DETH-COF < NiPor-DETH-COF < ZnPor-DETH-COF. Based on the detailed experiments and calculations, this tunable performance can be mainly explained by their tailored charge-carrier dynamics via molecular engineering. This study not only represents a simple and effective way for efficient tuning of the photocatalytic hydrogen evolution activities of covalent organic frameworks at molecular level, but also provides valuable insight on the structure design of covalent organic frameworks for better photocatalysis.
Transcription organizes euchromatin via microphase separation
Authors: Hilbert Lennart , Sato Yuko , Kuznetsova Ksenia , Bianucci Tommaso , Kimura Hiroshi , Jülicher Frank , Honigmann Alf , Zaburdaev Vasily , Vastenhouw Nadine L.
Published: March 2021

In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA. Euchromatin, which is permissive for transcription, is spatially organized into transcriptionally inactive domains interspersed with pockets of transcriptional activity. While transcription and RNA have been implicated in euchromatin organization, it remains unclear how their interplay forms and maintains transcription pockets. Here we combine theory and experiment to analyze the dynamics of euchromatin organization as pluripotent zebrafish cells exit mitosis and begin transcription. We show that accumulation of RNA induces formation of transcription pockets which displace transcriptionally inactive chromatin. We propose that the accumulating RNA recruits RNA-binding proteins that together tend to separate from transcriptionally inactive euchromatin. Full phase separation is prevented because RNA remains tethered to transcribed euchromatin through RNA polymerases. Instead, smaller scale microphases emerge that do not grow further and form the typical pattern of euchromatin organization.
Structure of mammalian Mediator complex reveals Tail module architecture and interaction with a conserved core
Authors: Zhao Haiyan , Young Natalie , Kalchschmidt Jens , Lieberman Jenna , El Khattabi Laila , Casellas Rafael , Asturias Francisco J.
Published: March 2021

The Mediator complex plays an essential and multi-faceted role in regulation of RNA polymerase II transcription in all eukaryotes. Structural analysis of yeast Mediator has provided an understanding of the conserved core of the complex and its interaction with RNA polymerase II but failed to reveal the structure of the Tail module that contains most subunits targeted by activators and repressors. Here we present a molecular model of mammalian (Mus musculus) Mediator, derived from a 4.0 Å resolution cryo-EM map of the complex. The mammalian Mediator structure reveals that the previously unresolved Tail module, which includes a number of metazoan specific subunits, interacts extensively with core Mediator and has the potential to influence its conformation and interactions.
Photoresponsive supramolecular coordination polyelectrolyte as smart anticounterfeiting inks
Authors: Li Zhiqiang , Liu Xiao , Wang Guannan , Li Bin , Chen Hongzhong , Li Huanrong , Zhao Yanli
Published: March 2021

While photoluminescence printing is a widely applied anticounterfeiting technique, there are still challenges in developing new generation anticounterfeiting materials with high security. Here we report the construction of a photoresponsive supramolecular coordination polyelectrolyte (SCP) through hierarchical self-assembly of lanthanide ion, bis-ligand and diarylethene unit, driven by metal-ligand coordination and ionic interaction. Owing to the conformation-dependent photochromic fluorescence resonance energy transfer between the lanthanide donor and diarylethene acceptor, the ring-closure/ring-opening isomerization of the diarylethene unit leads to a photoreversible luminescence on/off switch in the SCP. The SCP is then utilized as security ink to print various patterns, through which photoreversible multiple information patterns with visible/invisible transformations are realized by simply alternating the irradiation with UV and visible light. This work demonstrates the possibility of developing a new class of smart anticounterfeiting materials, which could be operated in a noninvasive manner with a higher level of security.
Genome editing reveals fitness effects of a gene for sexual dichromatism in Sulawesian fishes
Authors: Ansai Satoshi , Mochida Koji , Fujimoto Shingo , Mokodongan Daniel F. , Sumarto Bayu Kreshna Adhitya , Masengi Kawilarang W. A. , Hadiaty Renny K. , Nagano Atsushi J. , Toyoda Atsushi , Naruse Kiyoshi , Yamahira Kazunori , Kitano Jun
Published: March 2021

Sexual selection drives rapid phenotypic diversification of mating traits. However, we know little about the causative genes underlying divergence in sexually selected traits. Here, we investigate the genetic basis of male mating trait diversification in the medaka fishes (genusOryzias) from Sulawesi, Indonesia. Using linkage mapping, transcriptome analysis, and genome editing, we identifycsf1as a causative gene for red pectoral fins that are unique to maleOryzias woworae. Acis-regulatory mutation enables androgen-induced expression ofcsf1in male fins.csf1-knockout males have reduced red coloration and require longer for mating, suggesting that coloration can contribute to male reproductive success. Contrary to expectations, non-red males are more attractive to a predatory fish than are red males. Our results demonstrate that integrating genomics with genome editing enables us to identify causative genes underlying sexually selected traits and provides a new avenue for testing theories of sexual selection.
Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations
Authors: Iyengar Neil M. , Zhou Xi Kathy , Mendieta Hillary , El-Hely Omar , Giri Dilip D. , Winston Lisle , Falcone Domenick J. , Wang Hanhan , Meng Lingsong , Ha Taehoon , Pollak Michael , Morrow Monica , Dannenberg Andrew J.
Published: March 2021

Obesity is associated with an increased risk of breast cancer in post-menopausal women and decreased risk in pre-menopausal women. Conversely, in BRCA1/2 mutation carriers, pre-menopausal obesity is associated with early-onset breast cancer. Here we show that obese, pre-menopausal BRCA1/2 mutation carriers have increased levels of aromatase and inflammation in the breast, as occurs in post-menopausal women. In a prospective cohort study of 141 women with germline BRCA1 (n = 74) or BRCA2 (n = 67) mutations, leptin, and aromatase expression were higher in the breast tissue of obese versus lean individuals (P < 0.05). Obesity was associated with breast white adipose tissue inflammation, which correlated with breast aromatase levels (P < 0.01). Circulating C-reactive protein, interleukin-6, and leptin positively correlated with body mass index and breast aromatase levels, whereas negative correlations were observed for adiponectin and sex hormone-binding globulin (P < 0.05). These findings could help explain the increased risk of early-onset breast cancer in obese BRCA1/2 mutation carriers.
Lymphovascular invasion, race, and the 21-gene recurrence score in early estrogen receptor-positive breast cancer
Authors: Makower Della , Lin Juan , Xue Xiaonan , Sparano Joseph A.
Published: March 2021

Lymphovascular invasion (LVI) and Black race are associated with poorer prognosis in early breast cancer (EBC). We evaluated the association between LVI and race, and whether LVI adds prognostic benefit to the 21-gene recurrence score (RS) in EBC. Women with ER+ HER2− EBC measuring up to 5 cm, with 0–3 involved axillary nodes, diagnosed between 1 January 2010 and 1 January 2014, who underwent surgery as first treatment and had available RS, were identified in the NCDB database. Bivariate associations between two categorical variables were examined using chi-square test. Multivariate Cox proportional hazards model were used to assess the association of LVI, race, and other covariates with overall survival (OS). 77,425 women, 65,018 node-negative (N0), and 12,407 with 1–3 positive (N+) nodes, were included. LVI was present in 12.7%, and associated with poor grade, RS 26–100, and N+ (all p < 0.0001), but not Black race. In multivariate analysis, LVI was associated with worse OS in N0 [HR 1.37 (95% CI 1.27, 1.57], but not N+ EBC. LVI was associated with worse OS in N0 patients with RS 11–25 [HR 1.31 (95% CI 1.09, 1.57)] and ≥26 [HR 1.58 (95% CI 1.30, 1.93)], but not RS 0–10. No interaction between LVI and chemotherapy benefit was seen. Black race was associated with worse OS in N0 (HR 1.21, p = 0.009) and N+ (HR 1.37, p = 0.015) disease. LVI adds prognostic information in ER+, HER2−, N0 BCA with RS 11–100, but does not predict chemotherapy benefit. Black race is associated with worse OS, but not LVI.
High-power amplified spontaneous emission pulses with tunable coherence for efficient non-linear processes
Authors: Valero Nicolas , Marion Denis , Lhermite Jerome , Delagnes Jean-Christophe , Renard William , Royon Romain , Cormier Eric
Published: March 2021

We report on a detailed study of an amplified spontaneous emission source operated in a pulsed regime with particular attention paid to the influence of high-intensity chaotic temporal events on the generation of nonlinear processes. To this aim, we have developed a monolithic high-power fiber system delivering partially coherent pulses of adjustable coherence. We also have demonstrated a non-linear method to characterize the stochastic properties of the source mitigating the bandwidth limitation of linear techniques. Measured parameters of the source for various configurations are presented. An enhanced classical model has been established to reproduce the statistical properties of the source and predict the behaviour when exciting non-linear processes. Finally, a non-linear process (second harmonic generation) is investigated comparing the efficiency when the process is pumped by a pulsed beam with maximal and low coherence.
Gas chromatography techniques to evaluate the hydrogen permeation characteristics in rubber: ethylene propylene diene monomer
Authors: Jung Jae Kap , Kim In Gyoo , Chung Ki Soo , Baek Un Bong
Published: March 2021

We established an ex-situ technique for evaluating hydrogen gas permeability by thermal desorption analysis (TDA) gas chromatography (GC) and by self-developed diffusion analysis software. Absorbed hydrogen mass in rubber, related to the GC-peak area, is recorded as a function of elapsed time after decompressing the hydrogen under high-pressure. From the charging amount (CH0) and diffusivity (D) obtained by the developed diffusion analysis program, the solubility(S) and permeability(P) is evaluated via Henry’s law and P = SD, respectively. The techniques were applied to ethylene propylene diene monomer (EPDM) rubber, sealing material candidates in hydrogen infrastructures. EPDM sample mixed with carbon black fillers showed dual hydrogen diffusion behaviors, whereas EPDM sample without carbon black showed a single hydrogen diffusion behavior. There was no appreciable pressure or size dependence on D, S and P. P are consistent with that measured by different researcher within the expanded uncertainty.
3D reconstruction of structures of hatched larva and young juvenile of the larvacean Oikopleura dioica using SBF-SEM
Authors: Nishida Hiroki , Ohno Nobuhiko , Caicci Federico , Manni Lucia
Published: March 2021

The larvaceanOikopleura dioicais a planktonic chordate and an emerging model organism with a short life cycle of 5 days that belongs toTunicata (Urochordata), the sister clade of vertebrates. It is characterized by the rapid development of a tadpole-shaped body. Organ formation in the trunk proceeds within 7 h after the hatching of the tailbud larvae at 3 h after fertilization (hpf) and is completed at 10 hpf, giving rise to fully functional juveniles as miniature adult form. Serial block face scanning electron microscopy was used to acquire ~ 2000 serial transverse section images of a 3 hpf larva and a 10 hpf juvenile to characterize the structures and cellular composition of the trunk and organs using 3D images and movies. Germ cells were found to fuse and establish a central syncytial cell in the gonad as early as 10 hpf. Larval development gave rise to functional organs after several rounds of cell division through trunk morphogenesis. The feature would makeO. dioicaideal for analyzing cellular behaviors during morphogenetic processes using live imaging. The detailed descriptions of the larvae and juveniles provided in this study can be utilized as the start and end points of organ morphogenesis in this rapidly developing organism.
Ferritin is associated with the severity of lung involvement but not with worse prognosis in patients with COVID-19: data from two Italian COVID-19 units
Authors: Carubbi Francesco , Salvati Lia , Alunno Alessia , Maggi Fabio , Borghi Erika , Mariani Rinalda , Mai Francesca , Paoloni Maurizio , Ferri Claudio , Desideri Giovambattista , Cicogna Sabrina , Grassi Davide
Published: March 2021

The coronavirus 2019 disease (COVID-19) is characterised by a heterogeneous clinical presentation, a complex pathophysiology and a wide range of imaging findings, depending on disease severity and time course. We conducted a retrospective evaluation of hospitalized patients with proven SARS-CoV-2 infection, clinical signs of COVID-19 and computed tomography (CT) scan-proven pulmonary involvement, in order to identify relationships between clinical, serological, imaging data and disease outcomes in patients with COVID-19. Clinical and serological records of patients admitted to two COVID-19 Units of the Abruzzo region in Italy with proven SARS-CoV-2 pulmonary involvement investigated with CT scan, assessed at the time of admission to the hospital, were retrospectively evaluated. Sixty-one patients (22 females and 39 males) of median age 65 years were enrolled. Fifty-six patients were discharged while death occurred in 5 patients. None of the lung abnormalities detected by CT was different between discharged and deceased patients. No differences were observed in the features and extent of pulmonary involvement according to age and gender. Logistic regression analysis with age and gender as covariates demonstrated that ferritin levels over the 25th percentile were associated with the involvement of all 5 pulmonary lobes (OR = 14.5, 95% CI 2.3–90.9, p = 0.004), the presence of septal thickening (OR = 8.2, 95% CI 1.6–40.9, p = 0.011) and the presence of mediastinal lymph node enlargement (OR = 12.0, 95% CI 1.1–127.5, p = 0.039) independently of age and gender. We demonstrated that ferritin levels over the 25th percentile are associated with a more severe pulmonary involvement, independently of age and gender and not associated with disease outcomes. The identification of reliable biomarkers in patients with COVID-19 may help guiding clinical decision, tailoring therapeutic approaches and ultimately improving the care and prognosis of patients with this disease.
A coffee berry borer (Hypothenemus hampei) genome assembly reveals a reduced chemosensory receptor gene repertoire and male-specific genome sequences
Authors: Navarro-Escalante Lucio , Hernandez-Hernandez Erick M. , Nuñez Jonathan , Acevedo Flor E. , Berrio Alejandro , Constantino Luis M. , Padilla-Hurtado Beatriz E. , Molina Diana , Gongora Carmenza , Acuña Ricardo , Stuart Jeff , Benavides Pablo
Published: March 2021

Coffee berry borer—CBB (Hypothenemus hampei) is a globally important economic pest of coffee (Coffea spp.). Despite current insect control methods for managing CBB, development of future control strategies requires a better understanding of its biology and interaction with its host plant. Towards this objective, we performed de novo CBB genome and transcriptome sequencing, improved CBB genome assembly and predicted 18,765 protein-encoding genes. Using genome and transcriptome data, we annotated the genes associated with chemosensation and found a reduced gene repertoire composed by 67 odorant receptors (ORs), 62 gustatory receptors (GRs), 33 ionotropic receptors (IRs) and 29 odorant-binding proteins (OBPs). In silico transcript abundance analysis of these chemosensory genes revealed expression enrichment in CBB adults compared with larva. Detection of differentially expressed chemosensory genes between males and females is likely associated with differences in host-finding behavior between sexes. Additionally, we discovered male-specific genome content and identified candidate male-specific expressed genes on these scaffolds, suggesting that a Y-like chromosome may be involved in the CBB’s functional haplodiploid mechanism of sex determination.
Human METTL7B is an alkyl thiol methyltransferase that metabolizes hydrogen sulfide and captopril
Authors: Maldonato Benjamin J. , Russell Drake A. , Totah Rheem A.
Published: March 2021

Methylation of alkyl thiols is a biotransformation pathway designed to reduce thiol reactivity and potential toxicity, yet the gene and protein responsible for human alkyl thiol methyltransferase (TMT) activity remain unknown. Here we demonstrate with a range of experimental approaches using cell lines, in vitro systems, and recombinantly expressed enzyme, that human methyltransferase-like protein 7B (METTL7B) catalyzes the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to hydrogen sulfide (H2S) and other exogenous thiol small molecules. METTL7B gene modulation experiments, including knockdown in HepG2 cells and overexpression in HeLa cells, directly alter the methylation of the drug captopril, a historic probe substrate for TMT activity. Furthermore, recombinantly expressed and purified wild-type METTL7B methylates several thiol compounds, including H2S, 7α-thiospironolactone, l-penicillamine, and captopril, in a time- and concentration-dependent manner. Typical for AdoMet-dependent small molecule methyltransferases, S-adenosyl-l-homocysteine (AdoHcy) inhibited METTL7B activity in a competitive fashion. Similarly, mutating a conserved aspartate residue, proposed to anchor AdoMet into the active site, to an alanine (D98A) abolished methylation activity. Endogenous thiols such as glutathione and cysteine, or classic substrates for other known small molecule S-, N-, and O-methyltransferases, were not substrates for METTL7B. Our results confirm, for the first time, that METTL7B, a gene implicated in multiple disease states including rheumatoid arthritis and breast cancer, encodes a protein that methylates small molecule alkyl thiols. Identifying the catalytic function of METTL7B will enable future pharmacological research in disease pathophysiology where altered METTL7B expression and, potentially H2S levels, can disrupt cell growth and redox state.
Deep learning approaches for challenging species and gender identification of mosquito vectors
Authors: Kittichai Veerayuth , Pengsakul Theerakamol , Chumchuen Kemmapon , Samung Yudthana , Sriwichai Patchara , Phatthamolrat Natthaphop , Tongloy Teerawat , Jaksukam Komgrit , Chuwongin Santhad , Boonsang Siridech
Published: March 2021

Microscopic observation of mosquito species, which is the basis of morphological identification, is a time-consuming and challenging process, particularly owing to the different skills and experience of public health personnel. We present deep learning models based on the well-known you-only-look-once (YOLO) algorithm. This model can be used to simultaneously classify and localize the images to identify the species of the gender of field-caught mosquitoes. The results indicated that the concatenated two YOLO v3 model exhibited the optimal performance in identifying the mosquitoes, as the mosquitoes were relatively small objects compared with the large proportional environment image. The robustness testing of the proposed model yielded a mean average precision and sensitivity of 99% and 92.4%, respectively. The model exhibited high performance in terms of the specificity and accuracy, with an extremely low rate of misclassification. The area under the receiver operating characteristic curve (AUC) was 0.958 ± 0.011, which further demonstrated the model accuracy. Thirteen classes were detected with an accuracy of 100% based on a confusion matrix. Nevertheless, the relatively low detection rates for the two species were likely a result of the limited number of wild-caught biological samples available. The proposed model can help establish the population densities of mosquito vectors in remote areas to predict disease outbreaks in advance.
Phase I dose escalation study of sorafenib plus S-1 for advanced solid tumors
Authors: Tsai Hui-Jen , Shiah Her-Shyong , Chang Jang-Yang , Su Wu-Chou , Chiang Nai-Jung , Chen Li-Tzong
Published: March 2021

S-1, an oral pyrimidine fluoride-derived agent, is effective against various cancers. Sorafenib, an oral multikinase inhibitor, was found to prolong the survival of various cancers and enhance the cytotoxicity of chemotherapeutic agents. We conducted a phase I dose escalation study to determine dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of S-1 when combined with sorafenib for refractory solid tumors. Eligible patients received escalating doses (30, 35, and 40 mg/m2 bid) of S-1 Day 1 (D1)–D14 and continuous sorafenib 400 mg bid from cycle 1 D8 every 21 days in a standard 3 + 3 study design. Primary endpoint was MTD. Thirteen patients were enrolled between May 2010 and Feb 2012. DLT developed in two (one grade 3 erythema and one prolonged grade 2 hand-foot-skin reaction) of the 6 patients at 35 mg/m2 dose level. One pancreatic neuroendocrine tumor (pNET) patient achieved a durable partial response (27.9 months). Four colon cancer patients had stable disease and 3 of them had progression-free survival greater than 6 months. This study determined the recommended (MTD) S-1 dose of 30 mg/m2 bid for this regimen. This result warrants further phase II studies for advanced pNET and colon cancer to evaluate the efficacy of this combination.
Novel proton conducting core–shell PAMPS-PVBS@Fe2TiO5 nanoparticles as a reinforcement for SPEEK based membranes
Authors: Salarizadeh Parisa , Javanbakht Mehran , Askari Mohammad Bagher , Hooshyari Khadijeh , Moradi Morteza , Beydaghi Hossein , Rastgoo-Deylami Mohadese , Enhessari Morteza
Published: March 2021

In this study, new nanocomposite membranes from sulfonated poly (ether ether ketone) (SPEEK) and proton-conducting Fe2TiO5 nanoparticles are prepared by the solution casting method. Sulfonated core–shell Fe2TiO5 nanoparticles are synthesized by redox polymerization. Therefore, 4-Vinyl benzene sulfonate (VBS) and 2-acrylamide-2-methyl-1-propane sulfonic acid (AMPS) are grafted on the surface of nanoparticles through radical polymerization. The different amounts of hybrid nanoparticles (PAMPS@Fe2TiO5 and PVBS@Fe2TiO5) are incorporated into the SPEEK matrix. The results show higher proton conductivity for all prepared nanocomposites than that of the SPEEK membrane. Embedding the sulfonated Fe2TiO5 nanoparticles into the SPEEK membrane improves proton conductivity by creating the new proton conducting sites. Besides, the nanocomposite membranes showed improved mechanical and dimensional stability in comparison with that of the SPEEK membrane. Also, the membranes including 2 wt% of PAMPS@Fe2TiO5 and PVBS@Fe2TiO5 nanoparticles indicate the maximum power density of 247 mW cm−2 and 226 mW cm−2 at 80 °C, respectively, which is higher than that of for the pristine membrane. Our prepared membranes have the potential for application in polymer electrolyte fuel cells.
Involvement of the vertebral artery in hemifacial spasm: clinical features and surgical strategy
Authors: Lee Seunghoon , Han Junghoon , Park Sang-Ku , Lee Jeong-A. , Joo Byung-Euk , Park Kwan
Published: March 2021

The vertebral artery (VA)-involved hemifacial spasm (HFS) has distinctive clinical features and performing microvascular decompression (MVD) is challenging. We described the clinical presentations of VA-involved HFS and the outcomes of MVD using the interposition method. Between January 2008 and March 2015, MVD was performed in 271 patients with VA-involved HFS. Demographic characteristics, preoperative severity, intraoperative findings, spasm-free outcome, and complications were retrospectively evaluated. A control group of 1500 consecutive patients with non-VA-involved HFS was enrolled. VA-involved HFS was associated with older age (p < 0.001), less female predominance (p < 0.001), more left-sided predominance (p < 0.001), and rapid symptom progression before MVD (p < 0.001). The Teflon Fulcrum method allowed intraoperative identification of the neurovascular compression site in 92.6% of the cases, and showed more severe indentation on the facial nerve (p < 0.001). Changes in the brainstem auditory evoked potentials during MVD (p < 0.001) and postoperative non-serviceable hearing loss (p < 0.001) were more frequent in patients with VA-involved than in non-VA-involved HFS. The spasm-free outcome and overall complication rates after MVD were not significantly different between the groups. VA-involved HFS has distinctive clinical features and poses a major surgical challenge for MVD success. The interposition method is a feasible surgical strategy in VA-involved HFS.
Restoration of amyloid PET images obtained with short-time data using a generative adversarial networks framework
Authors: Jeong Young Jin , Park Hyoung Suk , Jeong Ji Eun , Yoon Hyun Jin , Jeon Kiwan , Cho Kook , Kang Do-Young
Published: March 2021

Our purpose in this study is to evaluate the clinical feasibility of deep-learning techniques for F-18 florbetaben (FBB) positron emission tomography (PET) image reconstruction using data acquired in a short time. We reconstructed raw FBB PET data of 294 patients acquired for 20 and 2 min into standard-time scanning PET (PET20m) and short-time scanning PET (PET2m) images. We generated a standard-time scanning PET-like image (sPET20m) from a PET2m image using a deep-learning network. We did qualitative and quantitative analyses to assess whether the sPET20m images were available for clinical applications. In our internal validation, sPET20m images showed substantial improvement on all quality metrics compared with the PET2m images. There was a small mean difference between the standardized uptake value ratios of sPET20m and PET20m images. A Turing test showed that the physician could not distinguish well between generated PET images and real PET images. Three nuclear medicine physicians could interpret the generated PET image and showed high accuracy and agreement. We obtained similar quantitative results by means of temporal and external validations. We can generate interpretable PET images from low-quality PET images because of the short scanning time using deep-learning techniques. Although more clinical validation is needed, we confirmed the possibility that short-scanning protocols with a deep-learning technique can be used for clinical applications.
Optimism and pasture access in dairy cows
Authors: Crump Andrew , Jenkins Kirsty , Bethell Emily J. , Ferris Conrad P. , Kabboush Helen , Weller Jennifer , Arnott Gareth
Published: March 2021

Allowing dairy cattle to access pasture can promote natural behaviour and improve their health. However, the psychological benefits are poorly understood. We compared a cognitive indicator of emotion in cattle either with or without pasture access. In a crossover experiment, 29 Holstein–Friesian dairy cows had 18 days of overnight pasture access and 18 days of full-time indoor housing. To assess emotional wellbeing, we tested cows on a spatial judgement bias task. Subjects learnt to approach a rewarded bucket location, but not approach another, unrewarded bucket location. We then presented cows with three “probe” buckets intermediate between the trained locations. Approaching the probes reflected an expectation of reward under ambiguity—an “optimistic” judgement bias, suggesting positive emotional states. We analysed the data using linear mixed-effects models. There were no treatment differences in latency to approach the probe buckets, but cows approached the known rewarded bucket slower when they had pasture access than when they were indoors full-time. Our results indicate that, compared to cattle housed indoors, cattle with pasture access display less anticipatory behaviour towards a known reward. This reduced reward anticipation suggests that pasture is a more rewarding environment, which may induce more positive emotional states than full-time housing.
Assessment of the embolization effect of temperature-sensitive p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels in the rabbit renal artery by CT perfusion and confirmed by macroscopic examination
Authors: Zhang Zhen , Cen Chunyuan , Qian Kun , Li Han , Zhang Xin , Zhang Hongsen , Ma Guina , Chen Yan , Jiang Nanchuan , Zheng Chuansheng , Zhao Yanbing , Han Ping
Published: March 2021

Transcatheter embolization is an important treatment method in clinical therapy, and vascular embolization material plays a key role in embolization. The temperature-sensitive p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogel is a novel embolic agent. To evaluate the feasibility of the nanogel as a blood vessel embolization agent, we aimed to assess the effect of embolization with PIB nanogels in the rabbit renal artery by non-invasive computed tomography (CT) perfusion, macroscopic and histological examination. Ten healthy adult Japanese rabbits were used to implement RAE of PIB nanogels in their right kidneys. CT perfusion scans were performed pre- and post-treatment at various time-points (1, 4, 8, and 12 weeks). Two rabbits were euthanized and histologically examined at each time-point, and the remaining rabbits were euthanized at 12 weeks after embolization. The RAE efficacy of the nanogels was further confirmed by macroscopic and histological examination. The renal volume and renal blood flow (BF) of the right kidney were significantly decreased post-treatment compared with those pre-treatment (volume: pre, 9278 ± 1736 mm3; post 1 week, 5155 ± 979 mm3, P < 0.0001; post 4 weeks, 3952 ± 846 mm3, P < 0.0001; post 8 weeks, 3226 ± 556 mm3, P < 0.0001; post 12 weeks, 2064 ± 507 mm3, P < 0.0001. BF: pre, 530.81 ± 51.50 ml/min/100 ml; post 1 week, 0 ml/min/100 ml, P < 0.0001; post 4 weeks, 0 ml/min/100 ml, P < 0.0001; post 8 weeks, 0 ml/min/100 ml, P < 0.0001; post 12 weeks, 0 ml/min/100 ml, P < 0.0001). No revascularization or collateral circulation was observed on histological examination during this period, and PIB nanogels were dispersed in all levels of the renal arteries. Twelve weeks after embolization, CT perfusion showed no BF in the right renal artery and renal tissue, a finding that was consistent with histological examination showing complete embolization of the right renal artery with a lack of formation of collateral vessels. The effect of embolization on PIB was adequate, with good dispersion and permanency, and could be evaluated by non-invasive and quantitative CT perfusion.
Synthesis and characterization of Na-P1 (GIS) zeolite using a kaolinitic rock
Authors: Novembre Daniela , Gimeno Domingo , Del Vecchio Alessandro
Published: March 2021

This work focuses on the hydrothermal synthesis of Na-P1 zeolite by using a kaolinite rock coming from Romana (Sassari, Italy). The kaolin is calcined at a temperature of 650 °C and then mixed with calculated quantities of NaOH. The synthesis runs are carried out at ambient pressure and at variable temperatures of 65 and 100 °C. For the first time compared to the past, the Na-P1 zeolite is synthesized without the use of additives and through a protocol that reduces both temperatures and synthesis times. The synthesis products are analysed by X-ray diffraction, high temperature X-ray diffraction, infrared spectroscopy, scanning electron microscopy and inductively coupled plasma optical emission spectrometry. The cell parameters are calculated using the Rietveld method. Density and specific surface area are also calculated. The absence of amorphous phases and impurities in synthetic powders is verified through quantitative phase analysis using the combined Rietveld and reference intensity ratio methods. The results make the experimental protocol very promising for an industrial transfer.
Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations
Authors: Nusinovici Simon , Sabanayagam Charumathi , Lee Kristine E. , Zhang Liang , Cheung Carol Y. , Tai E. Shyong , Tan Gavin S. W. , Cheng Ching Yu , Klein Barbara E. K. , Wong Tien Yin
Published: March 2021

The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascular caliber (arteriolar—CRAE, and venular—CRVE) and diabetic retinopathy (DR). Incident cases of DKD were identified after ~ 6-year. Incident cases were defined based on eGFR in SEED and proteinuria or history of renal dialysis in WESDR. The incidence of DKD were 11.8% in SEED and 14.0% in WESDR. Wider CRAE in SEED (OR = 1.58 [1.02, 2.45]) and wider CRVE (OR = 1.69 [1.02, 2.80)) in WESDR were associated with increased risk of DKD. Presence of DR was associated with an increased risk of DKD in both cohorts (SEED: OR = 1.91 [1.21, 3.01] in SEED, WESDR: OR = 1.99 [1.18, 3.35]). Adding DR and retinal vascular calibers in the model beyond traditional risk factors led to an improvement of predictive performance of DKD risk between 1.1 and 2.4%; and improved classification (NRI 3 between 9%). Microvascular changes in the retina are longitudinally associated with risk of DKD.