bluuebunny/crossref_metadata_2025 huggingface dataset:
The associations of maternal and paternal obesity with latent patterns of offspring BMI development between 7 and 17 years of age: pooled analyses of cohorts born in 1958 and 2001 in the United Kingdom
Authors: Johnson William , Pereira Snehal M. Pinto , Costa Silvia , Baker Jennifer L. , Norris Tom
Published: November 2022

Objective

We aimed to 1) describe how the UK obesity epidemic reflects a change over time in the proportion of the population demonstrating adverse latent patterns of BMI development and 2) investigate the potential roles of maternal and paternal BMI in this secular process.

Methods

We used serial BMI data between 7 and 17 years of age from 13220 boys and 12711 girls. Half the sample was born in 1958 and half in 2001. Sex-specific growth mixture models were developed. The relationships of maternal and paternal BMI and weight status with class membership were estimated using the 3-step BCH approach, with covariate adjustment.

Results

The selected models had five classes. For each sex, in addition to the two largest normal weight classes, there were “normal weight increasing to overweight” (17% of boys and 20% of girls), “overweight increasing to obesity” (8% and 6%), and “overweight decreasing to normal weight” (3% and 6%) classes. More than 1-in-10 children from the 2001 birth cohort were in the “overweight increasing to obesity” class, compared to less than 1-in-30 from the 1958 birth cohort. Approximately 75% of the mothers and fathers of this class had overweight or obesity. When considered together, both maternal and paternal BMI were associated with latent class membership, with evidence of negative departure from additivity (i.e., the combined effect of maternal and paternal BMI was smaller than the sum of the individual effects). The odds of a girl belonging to the “overweight increasing to obesity” class (compared to the largest normal weight class) was 13.11 (8.74, 19.66) times higher if both parents had overweight or obesity (compared to both parents having normal weight); the equivalent estimate for boys was 9.01 (6.37, 12.75).

Conclusions

The increase in obesity rates in the UK over more than 40 years has been partly driven by the growth of a sub-population demonstrating excess BMI gain during adolescence. Our results implicate both maternal and paternal BMI as correlates of this secular process.
Novel long noncoding RNA LINC02820 augments TNF signaling pathway to remodel cytoskeleton and potentiate metastasis in esophageal squamous cell carcinoma
Authors: Wang Jing , Huang Tie-Jun , Mei Yan , Luo Fei-Fei , Xie De-Huan , Peng Li-Xia , Liu Bao-Qi , Fan Mei-Ling , Zhang Jiang-Bo , Zheng Shu-Tao , Qian Chao-Nan , Huang Bi-Jun
Published: November 2022

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China. However, there are no targets to treat ESCC because the molecular mechanism behind the cancer is still unclear. Here, we found a novel long noncoding RNA LINC02820 was upregulated in ESCC and associated with the ESCC clinicopathological stage. Through a series of functional experiments, we observed that LINC02820 only promoted the migration and invasion capabilities of ESCC cell lines. Mechanically, we found that LINC02820 may affect the cytoskeletal remodeling, interact with splice factor 3B subunit 3 (SF3B3), and cooperate with TNFα to amplify the NF-κB signaling pathway, which can lead to ESCC metastasis. Overall, our findings revealed that LINC02820 is a potential biomarker and therapeutic target for the diagnosis and treatment of ESCC.
Novel protein complexes containing autophagy and UPS components regulate proteasome-dependent PARK2 recruitment onto mitochondria and PARK2-PARK6 activity during mitophagy
Authors: Kocaturk Nur Mehpare , Peker Nesibe , Eberhart Karin , Akkoc Yunus , Deveci Gamze , Dengjel Joern , Gozuacik Devrim
Published: November 2022

Autophagy is an evolutionarily conserved eukaryotic cellular mechanism through which cytosolic fragments, misfolded/aggregated proteins and organelles are degraded and recycled. Priming of mitochondria through ubiquitylation is required for the clearance the organelle by autophagy (mitophagy). Familial Parkinson’s Disease-related proteins, including the E3-ligase PARK2 (PARKIN) and the serine/threonine kinase PARK6 (PINK1) control these ubiquitylation reactions and contribute to the regulation of mitophagy. Here we describe, novel protein complexes containing autophagy protein ATG5 and ubiquitin-proteasome system (UPS) components. We discovered that ATG5 interacts with PSMA7 and PARK2 upon mitochondrial stress. Results suggest that all three proteins translocate mitochondria and involve in protein complexes containing autophagy, UPS and mitophagy proteins. Interestingly, PARK2 and ATG5 recruitment onto mitochondria requires proteasome components PSMA7 and PSMB5. Strikingly, we discovered that subunit of 20 S proteasome, PSMA7, is required for the progression of PARK2-PARK6-mediated mitophagy and the proteasome activity following mitochondrial stress. Our results demonstrate direct, dynamic and functional interactions between autophagy and UPS components that contribute to the regulation of mitophagy.
Emergence of distinct electronic states in epitaxially-fused PbSe quantum dot superlattices
Authors: Kavrik Mahmut S. , Hachtel Jordan A. , Ko Wonhee , Qian Caroline , Abelson Alex , Unlu Eyup B. , Kashyap Harshil , Li An-Ping , Idrobo Juan C. , Law Matt
Published: November 2022

Quantum coupling in arrayed nanostructures can produce novel mesoscale properties such as electronic minibands to improve the performance of optoelectronic devices, including ultra-efficient solar cells and infrared photodetectors. Colloidal PbSe quantum dots (QDs) that self-assemble into epitaxially-fused superlattices (epi-SLs) are predicted to exhibit such collective phenomena. Here, we show the emergence of distinct local electronic states induced by crystalline necks that connect individual PbSe QDs and modulate the bandgap energy across the epi-SL. Multi-probe scanning tunneling spectroscopy shows bandgap modulation from 0.7 eV in the QDs to 1.1 eV at their necks. Complementary monochromated electron energy-loss spectroscopy demonstrates bandgap modulation in spectral mapping, confirming the presence of these distinct energy states from necking. The results show the modification of the electronic structure of a precision-made nanoscale superlattice, which may be leveraged in new optoelectronic applications.
An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington’s disease patient neurons
Authors: Krach Florian , Stemick Judith , Boerstler Tom , Weiss Alexander , Lingos Ioannis , Reischl Stephanie , Meixner Holger , Ploetz Sonja , Farrell Michaela , Hehr Ute , Kohl Zacharias , Winner Beate , Winkler Juergen
Published: November 2022

Huntington’s disease (HD) is a neurodegenerative disorder caused by poly-Q expansion in the Huntingtin (HTT) protein. Here, we delineate elevated mutant HTT (mHTT) levels in patient-derived cells including fibroblasts and iPSC derived cortical neurons using mesoscale discovery (MSD) HTT assays. HD patients’ fibroblasts and cortical neurons recapitulate aberrant alternative splicing as a molecular fingerprint of HD. Branaplam is a splicing modulator currently tested in a phase II study in HD (NCT05111249). The drug lowers total HTT (tHTT) and mHTT levels in fibroblasts, iPSC, cortical progenitors, and neurons in a dose dependent manner at an IC50 consistently below 10 nM without inducing cellular toxicity. Branaplam promotes inclusion of non-annotated novel exons. Among these Branaplam-induced exons, there is a 115 bp frameshift-inducing exon in the HTT transcript. This exon is observed upon Branaplam treatment in Ctrl and HD patients leading to a profound reduction of HTT RNA and protein levels. Importantly, Branaplam ameliorates aberrant alternative splicing in HD patients’ fibroblasts and cortical neurons. These findings highlight the applicability of splicing modulators in the treatment of CAG repeat disorders and decipher their molecular effects associated with the pharmacokinetic and -dynamic properties in patient-derived cellular models.
Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers
Authors: Cantley Jennifer , Ye Xiaofen , Rousseau Emma , Januario Tom , Hamman Brian D. , Rose Christopher M. , Cheung Tommy K. , Hinkle Trent , Soto Leofal , Quinn Connor , Harbin Alicia , Bortolon Elizabeth , Chen Xin , Haskell Roy , Lin Eva , Yu Shang-Fan , Del Rosario Geoff , Chan Emily , Dunlap Debra , Koeppen Hartmut , Martin Scott , Merchant Mark , Grimmer Matt , Broccatelli Fabio , Wang Jing , Pizzano Jennifer , Dragovich Peter S. , Berlin Michael , Yauch Robert L.
Published: November 2022

The mammalian SWItch/Sucrose Non-Fermentable (SWI/SNF) helicase SMARCA4 is frequently mutated in cancer and inactivation results in a cellular dependence on its paralog, SMARCA2, thus making SMARCA2 an attractive synthetic lethal target. However, published data indicates that achieving a high degree of selective SMARCA2 inhibition is likely essential to afford an acceptable therapeutic index, and realizing this objective is challenging due to the homology with the SMARCA4 paralog. Herein we report the discovery of a potent and selective SMARCA2 proteolysis-targeting chimera molecule (PROTAC), A947. Selective SMARCA2 degradation is achieved in the absence of selective SMARCA2/4 PROTAC binding and translates to potent in vitro growth inhibition and in vivo efficacy in SMARCA4 mutant models, compared to wild type models. Global ubiquitin mapping and proteome profiling reveal no unexpected off-target degradation related to A947 treatment. Our study thus highlights the ability to transform a non-selective SMARCA2/4-binding ligand into a selective and efficacious in vivo SMARCA2-targeting PROTAC, and thereby provides a potential new therapeutic opportunity for patients whose tumors contain SMARCA4 mutations.
An improved 9 micron thick separator for a 350 Wh/kg lithium metal rechargeable pouch cell
Authors: Chang Zhi , Yang Huijun , Pan Anqiang , He Ping , Zhou Haoshen
Published: November 2022

The use of separators that are thinner than conventional separators (> 20 µm) would improve the energy densities and specific energies of lithium batteries. However, thinner separators increase the risk of internal short circuits from lithium dendrites formed in both lithium-ion and lithium metal batteries. Herein, we grow metal-organic frameworks (MOFs) inside the channels of a polypropylene separator (8 µm thick) using current-driven electrosynthesis, which aggregates the electrolyte in the MOF channels. Compared to unmodified polypropylene separators, the MOF-modified separator (9 µm thick) vastly improves the cycling stability and dendrite resistance of cells assembled with Li metal anodes and carbonate-based electrolytes. As a demonstration, a 354 Wh kg−1 pouch cell with a lithium metal anode and LiNi0.8Co0.15Al0.05O2 (NCA)-based cathode (N/P = 3.96) is assembled with 9 µm layer of the MOF-modified separator and retains 80% of its capacity after 200 cycles (charged at 75 mA g−1, discharged at 100 mA g−1) at 25 °C.
Mapping global dynamics of benchmark creation and saturation in artificial intelligence
Authors: Ott Simon , Barbosa-Silva Adriano , Blagec Kathrin , Brauner Jan , Samwald Matthias
Published: November 2022

Benchmarks are crucial to measuring and steering progress in artificial intelligence (AI). However, recent studies raised concerns over the state of AI benchmarking, reporting issues such as benchmark overfitting, benchmark saturation and increasing centralization of benchmark dataset creation. To facilitate monitoring of the health of the AI benchmarking ecosystem, we introduce methodologies for creating condensed maps of the global dynamics of benchmark creation and saturation. We curate data for 3765 benchmarks covering the entire domains of computer vision and natural language processing, and show that a large fraction of benchmarks quickly trends towards near-saturation, that many benchmarks fail to find widespread utilization, and that benchmark performance gains for different AI tasks are prone to unforeseen bursts. We analyze attributes associated with benchmark popularity, and conclude that future benchmarks should emphasize versatility, breadth and real-world utility.
The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma
Authors: Vdovin Alexander , Jelinek Tomas , Zihala David , Sevcikova Tereza , Durech Michal , Sahinbegovic Hana , Snaurova Renata , Radhakrishnan Dhwani , Turi Marcello , Chyra Zuzana , Popkova Tereza , Venglar Ondrej , Hrdinka Matous , Hajek Roman , Simicek Michal
Published: November 2022

Serum monoclonal immunoglobulin (Ig) is the main diagnostic factor for patients with multiple myeloma (MM), however its prognostic potential remains unclear. On a large MM patient cohort (n = 4146), we observe no correlation between serum Ig levels and patient survival, while amount of intracellular Ig has a strong predictive effect. Focused CRISPR screen, transcriptional and proteomic analysis identify deubiquitinase OTUD1 as a critical mediator of Ig synthesis, proteasome inhibitor sensitivity and tumor burden in MM. Mechanistically, OTUD1 deubiquitinates peroxiredoxin 4 (PRDX4), protecting it from endoplasmic reticulum (ER)-associated degradation. In turn, PRDX4 facilitates Ig production which coincides with the accumulation of unfolded proteins and higher ER stress. The elevated load on proteasome ultimately potentiates myeloma response to proteasome inhibitors providing a window for a rational therapy. Collectively, our findings support the significance of the Ig production machinery as a biomarker and target in the combinatory treatment of MM patients.
Fully-exposed Pt-Fe cluster for efficient preferential oxidation of CO towards hydrogen purification
Authors: Jia Zhimin , Qin Xuetao , Chen Yunlei , Cai Xiangbin , Gao Zirui , Peng Mi , Huang Fei , Xiao Dequan , Wen Xiaodong , Wang Ning , Jiang Zheng , Zhou Wu , Liu Hongyang , Ma Ding
Published: November 2022

Hydrogen is increasingly being discussed as clean energy for the goal of net-zero carbon emissions, applied in the proton-exchange-membrane fuel cells (PEMFC). The preferential oxidation of CO (PROX) in hydrogen is a promising solution for hydrogen purification to avoid catalysts from being poisoned by the trace amount of CO in hydrogen-rich fuel gas. Here, we report the fabrication of a novel bimetallic Pt-Fe catalyst with ultralow metal loading, in which fully-exposed Pt clusters bonded with neighbor atomically dispersed Fe atoms on the defective graphene surface. The fully-exposed PtFe cluster catalyst could achieve complete elimination of CO through PROX reaction and almost 100% CO selectivity, while maintaining good stability for a long period. It has the mass-specific activity of 6.19 (molCO)*(gPt)−1*h−1at room temperature, which surpasses those reported in literatures. The exhaustive experimental results and theoretical calculations reveal that the construction of fully-exposed bimetallic Pt-Fe cluster catalysts with maximized atomic efficiency and abundant interfacial sites could facilitate oxygen activation on unsaturated Fe species and CO adsorption on electron-rich Pt clusters to hence the probability of CO oxidation, leading to excellent reactivity in practical applications.
Enormous-stiffness-changing polymer networks by glass transition mediated microphase separation
Authors: Chen Lie , Zhao Cong , Huang Jin , Zhou Jiajia , Liu Mingjie
Published: November 2022

The rapid development of flexible electronics and soft robotics has an urgent demand for materials with wide-range switchable stiffness. Here, we report a polymer network that can isochorically and reversibly switch between soft ionogel and rigid plastic accompanied by a gigantic stiffness change from about 600 Pa to 85 MPa. This transition is realized by introducing polymer vitrification to regulate the liquid–liquid phase separation, namely the Berghmans’ point in the phase diagram of binary gel systems. Regulating the Lewis acid-base interactions between polymer and ionic liquids, the stiffness-changing ratio of polymer network can be tuned from 10 to more than 105. These wide-range stiffness-changing ionogels show excellent shape adaptability and reconfigurability, which can enhance the interfacial adhesion between ionogel and electrode by an order of magnitude and reduce interfacial impedance by 75%.
Emergent ferromagnetism and insulator-metal transition in δ-doped ultrathin ruthenates
Authors: Ali Zeeshan , Saghayezhian Mohammad , Wang Zhen , O’Hara Andrew , Shin Donghan , Ge Wenbo , Chan Ying Ting , Zhu Yimei , Wu Weida , Pantelides Sokrates T. , Zhang Jiandi
Published: November 2022

Heterostructures of complex transition metal oxides are known to induce extraordinary emergent quantum states that arise from broken symmetry and other discontinuities at interfaces. Here we report the emergence of unusual, thickness-dependent properties in ultrathin CaRuO3 films by insertion of a single isovalent SrO layer (referred to as δ-doping). While bulk CaRuO3 is metallic and nonmagnetic, films thinner than or equal to ~15-unit cells (u.c.) are insulating though still nonmagnetic. However, δ-doping to middle of such CaRuO3 films induces an insulator-to-metal transition and unusual ferromagnetism with strong magnetoresistive behavior. Atomically resolved imaging and density-functional-theory calculations reveal that the whole δ-doped film preserves the bulk-CaRuO3 orthorhombic structure, while appreciable structural and electronic changes are highly localized near the SrO layer. The results highlight delicate nature of magnetic instability in CaRuO3 and subtle effects that can alter it, especially the role of A-site cation in electronic and magnetic structure additional to lattice distortion in ruthenates. It also provides a practical approach to engineer material systems via highly localized modifications in their structure and composition that may offer new routes to the design of oxide electronics.
Hierarchical optofluidic microreactor for water purification using an array of TiO2 nanostructures
Authors: Kim Hyejeong , Kwon Hyunah , Song Ryungeun , Shin Seonghun , Ham So-Young , Park Hee-Deung , Lee Jinkee , Fischer Peer , Bodenschatz Eberhard
Published: November 2022

Clean water for human consumption is, in many places, a scarce resource, and efficient schemes to purify water are in great demand. Here, we describe a method to dramatically increase the efficiency of a photocatalytic water purification microreactor. Our hierarchical optofluidic microreactor combines the advantages of a nanostructured photocatalyst with light harvesting by base substrates, together with a herringbone micromixer for the enhanced transport of reactants. The herringbone micromixer further improves the reaction efficiency of the nanostructured photocatalyst by generating counter-rotating vortices along the flow direction. In addition, the use of metal-based substrates underneath the nanostructured catalyst increases the purification capacity by improving the light-harvesting efficiency. The photocatalyst is grown from TiO2 as a nanohelix film, which exhibits a large surface-to-volume ratio and a reactive microstructure. We show that the hierarchical structuring with micro- to nanoscale features results in a device with markedly increased photocatalytic activity as compared with a solid unstructured catalyst surface. This is evidenced by the successful degradation of persistent aqueous contaminants, sulfamethoxazole, and polystyrene microplastics. The design can potentially be implemented with solar photocatalysts in flow-through water purification systems.
Stain-free identification of cell nuclei using tomographic phase microscopy in flow cytometry
Authors: Pirone Daniele , Lim Joowon , Merola Francesco , Miccio Lisa , Mugnano Martina , Bianco Vittorio , Cimmino Flora , Visconte Feliciano , Montella Annalaura , Capasso Mario , Iolascon Achille , Memmolo Pasquale , Psaltis Demetri , Ferraro Pietro
Published: November 2022

Quantitative phase imaging has gained popularity in bioimaging because it can avoid the need for cell staining, which, in some cases, is difficult or impossible. However, as a result, quantitative phase imaging does not provide the labelling of various specific intracellular structures. Here we show a novel computational segmentation method based on statistical inference that makes it possible for quantitative phase imaging techniques to identify the cell nucleus. We demonstrate the approach with refractive index tomograms of stain-free cells reconstructed using tomographic phase microscopy in the flow cytometry mode. In particular, by means of numerical simulations and two cancer cell lines, we demonstrate that the nucleus can be accurately distinguished within the stain-free tomograms. We show that our experimental results are consistent with confocal fluorescence microscopy data and microfluidic cyto-fluorimeter outputs. This is a remarkable step towards directly extracting specific three-dimensional intracellular structures from the phase contrast data in a typical flow cytometry configuration.
Detection of m6A from direct RNA sequencing using a multiple instance learning framework
Authors: Hendra Christopher , Pratanwanich Ploy N. , Wan Yuk Kei , Goh W. S. Sho , Thiery Alexandre , Göke Jonathan
Published: November 2022

RNA modifications such as m6A methylation form an additional layer of complexity in the transcriptome. Nanopore direct RNA sequencing can capture this information in the raw current signal for each RNA molecule, enabling the detection of RNA modifications using supervised machine learning. However, experimental approaches provide only site-level training data, whereas the modification status for each single RNA molecule is missing. Here we present m6Anet, a neural-network-based method that leverages the multiple instance learning framework to specifically handle missing read-level modification labels in site-level training data. m6Anet outperforms existing computational methods, shows similar accuracy as experimental approaches, and generalizes with high accuracy to different cell lines and species without retraining model parameters. In addition, we demonstrate that m6Anet captures the underlying read-level stoichiometry, which can be used to approximate differences in modification rates. Overall, m6Anet offers a tool to capture the transcriptome-wide identification and quantification of m6A from a single run of direct RNA sequencing.
A global dataset of pandemic- and epidemic-prone disease outbreaks
Authors: Torres Munguía Juan Armando , Badarau Florina Cristina , Díaz Pavez Luis Rodrigo , Martínez-Zarzoso Inmaculada , Wacker Konstantin M.
Published: November 2022

This paper presents a new dataset of infectious disease outbreaks collected from the Disease Outbreak News and the Coronavirus Dashboard produced by the World Health Organization. The dataset contains information on 70 infectious diseases and 2227 public health events that occurred over the period from January 1996 to March 2022 in 233 countries and territories around the world. We illustrate the potential use of this dataset to the research community by analysing the spatial distribution of disease outbreaks. We find evidence of spatial clusters of high incidences (“hot spots”) in Africa, America, and Asia. This spatial analysis enables policymakers to identify the regions with the greatest likelihood of suffering from disease outbreaks and, taking into account their degree of preparedness and vulnerability, to develop policies that may help contain the spreading of future outbreaks. Further applications could focus on combining our data with other information sources to study, for instance, the link between environmental, globalization, and/or socioeconomic factors with disease outbreaks.
Bacterial plasmid-associated and chromosomal proteins have fundamentally different properties in protein interaction networks
Authors: Downing Tim , Rahm Alexander
Published: November 2022

Plasmids facilitate horizontal gene transfer, which enables the diversification of pathogens into new anatomical and environmental niches, implying that plasmid-encoded genes can cooperate well with chromosomal genes. We hypothesise that such mobile genes are functionally different to chromosomal ones due to this ability to encode proteins performing non-essential functions like antimicrobial resistance and traverse distinct host cells. The effect of plasmid-driven gene gain on protein–protein interaction network topology is an important question in this area. Moreover, the extent to which these chromosomally- and plasmid-encoded proteins interact with proteins from their own groups compared to the levels with the other group remains unclear. Here, we examined the incidence and protein–protein interactions of all known plasmid-encoded proteins across representative specimens from most bacteria using all available plasmids. We found that plasmid-encoded genes constitute ~ 0.65% of the total number of genes per bacterial sample, and that plasmid genes are preferentially associated with different species but had limited taxonomical power beyond this. Surprisingly, plasmid-encoded proteins had both more protein–protein interactions compared to chromosomal proteins, countering the hypothesis that genes with higher mobility rates should have fewer protein-level interactions. Nonetheless, topological analysis and investigation of the protein–protein interaction networks' connectivity and change in the number of independent components demonstrated that the plasmid-encoded proteins had limited overall impact in > 96% of samples. This paper assembled extensive data on plasmid-encoded proteins, their interactions and associations with diverse bacterial specimens that is available for the community to investigate in more detail.
Evidence for compositionality in baboons (Papio papio) through the test case of negation
Authors: Dautriche Isabelle , Buccola Brian , Berthet Melissa , Fagot Joel , Chemla Emmanuel
Published: November 2022

Can non-human animals combine abstract representations much like humans do with language? In particular, can they entertain a compositional representation such as ‘not blue’? Across two experiments, we demonstrate that baboons (Papio papio) show a capacity for compositionality. Experiment 1 showed that baboons can entertain negative, compositional, representations: they can learn to associate a cue with iconically related referents (e.g., a blue patch referring to all blue objects), but also to the complement set associated with it (e.g., a blue patch referring to all non-blue objects). Strikingly, Experiment 2 showed that baboons not only learn to associate a cue with iconically related referents, but can learn to associate complex cues (composed of the same cue and an additional visual element) with the complement object set. Thus, they can learn an operation, instantiated by this additional visual element, that can be compositionally combined with previously learned cues. These results significantly reduce any claim that would make the manipulation and combination of abstract representations a solely human privilege.
Simplified inelastic electron tunneling spectroscopy based on low-noise derivatives
Authors: Kesarwani Shankar , Misra Shobhna , Saha Dipankar , Della Rocca Maria Luisa , Roy Indrajit , Ganguly Swaroop , Mahajan Ashutosh
Published: November 2022

A standard experimental setup for Inelastic Electron Tunneling Spectroscopy (IETS) performs the measurement of the second derivative of the current with respect to the voltage ($$d^2I/dV^2$$

d
2

I
/
d

V
2

) using a small AC signal and a lock-in based second harmonic detection. This avoids noise arising from direct differentiation of the current-voltage characteristics (I–V) by standard numerical methods. Here we demonstrate a noise-filtering algorithm based on Tikhonov Regularization to obtain IET spectra (i.e. $$d^2I/dV^2$$

d
2

I
/
d

V
2

vs. V) from measured DC I–V curves. This leads to a simple and effective numerical method for IETS extraction. We apply the algorithm to I–V data from a molecular junction and a metal-insulator-semiconductor tunneling device, demonstrating that the computed first/second derivatives have a workable match with those obtained from our lock-in measurements; the computed IET spectral peaks also correlate well with reported experimental ones. Finally, we present a scheme for automated tuning of the algorithm parameters well-suited for the use of this numerical protocol in real applications.
Characteristics of site-specific response using the measured data from seismic accelerometers in Pohang Yeongil New Port under 9.12 and Pohang earthquakes
Authors: Seo Jihye , Won Deokhee
Published: November 2022

Recently, medium-sized earthquakes such as the Gyeongju 9.12 earthquake (September 12, 2016, ML = 5.8) and the Pohang earthquake (November 15, 2017, ML = 5.4) occurred in Korea, thereby increasing social concern about earthquakes. Because Korea is not located near the Circum-Pacific Belt, also referred to as the “Ring of Fire”, people in Korea are not used to earthquake disasters. Coastal areas in Korea are lined with multiple mega-cities and major industrial facilities. Most of them constructed on landfill, they have a high threat level to the damage to populations and structures leading to complex disasters in the event of an earthquake. However, studies of seismic hazards in ports is incomplete compared with those of onshore sites. Improving the understanding of seismic hazards and characterizing them catching up with related research from various perspectives being actively conducted. In this study, the site-specific response characteristics of the Pohang International Container Terminal in Pohang Yeongil New Port were analyzed using the S-wave energy of 10 sets of ground motions recorded by seismic accelerometers operated by the Ministry of Oceans and Fisheries based on the horizontal-to-vertical spectral ratio (H/V ratio) method. As a result of analysis, the H/V ratio curves show that the peak frequency values for the target site averages 9 Hz, and the natural period values of the site were preliminarily predicted to average 0.11 s. In addition, site amplification characteristics are different based on the seismic wave calculation method. The result can be used as data for identifying ground dynamic characteristics and verifying the site amplification coefficients and design spectrum in the seismic design.
Loop-mediated isothermal amplification (LAMP) assay for specific and rapid detection of Dickeya fangzhongdai targeting a unique genomic region
Authors: DeLude Anuhea , Wells Riley , Boomla Sherine , Chuang Shu-Cheng , Urena Frank , Shipman Aaron , Rubas Noelle , Kuehu Donna Lee , Bickerton Buster , Peterson Taylor , Dobhal Shefali , Arizala Dario , Klair Diksha , Ochoa-Corona Francisco , Ali Md Emran , Odani Jenee , Bingham Jon-Paul , Jenkins Daniel M. , Fletcher Jacqueline , Stack James P. , Alvarez Anne M. , Arif Mohammad
Published: November 2022

Dickeya fangzhongdai, a bacterial pathogen of taro (Colocasia esculenta), onion (Allium sp.), and several species in the orchid family (Orchidaceae) causes soft rot and bleeding canker diseases. No field-deployable diagnostic tool is available for specific detection of this pathogen in different plant tissues. Therefore, we developed a field-deployable loop-mediated isothermal amplification (LAMP) assay using a unique genomic region, present exclusively in D. fangzhongdai. Multiple genomes of D. fangzhongdai, and other species of Dickeya, Pectobacterium and unrelated genera were used for comparative genomic analyses to identify an exclusive and conserved target sequence from the major facilitator superfamily (MFS) transporter gene region. This gene region had broad detection capability for D. fangzhongdai and thus was used to design primers for endpoint PCR and LAMP assays. In-silico validation showed high specificity with D. fangzhongdai genome sequences available in the NCBI GenBank genome database as well as the in-house sequenced genome. The specificity of the LAMP assay was determined with 96 strains that included all Dickeya species and Pectobacterium species as well as other closely related genera and 5 hosts; no false positives or false negatives were detected. The detection limit of the assay was determined by performing four sensitivity assays with tenfold serially diluted purified genomic DNA of D. fangzhongdai with and without the presence of crude host extract (taro, orchid, and onion). The detection limit for all sensitivity assays was 100 fg (18–20 genome copies) with no negative interference by host crude extracts. The assays were performed by five independent operators (blind test) and on three instruments (Rotor-Gene, thermocycler and dry bath); the assay results were concordant. The assay consistently detected the target pathogen from artificially inoculated and naturally infected host samples. The developed assay is highly specific for D. fangzhongdai and has applications in routine diagnostics, phytosanitary and seed certification programs, and epidemiological studies.
Hemorrhagic risk prediction in coronary artery disease patients based on photoplethysmography and machine learning
Authors: He Zhengling , Zhang Huajun , Chen Xianxiang , Shi Junshan , Bai Lu , Fang Zhen , Wang Rong
Published: November 2022

Hemorrhagic events are the main focus of attention during antithrombosis therapy in patients with coronary artery disease (CAD). This study aims to investigate the potential of using photoplethysmography (PPG) and machine learning techniques to assess hemorrhagic risk in patients with CAD. A total of 1638 patients with CAD were enrolled from January 2018 to October 2019, among which 114 patients were observed to have at least one positive event. Importantly, 102 patients with 9933 records were finally retained for analysis in this study. Participants were required to collect data using the portable PPG acquisition device and the specially designed Android APP. The data was collected and uploaded to a remote server. Based on collected PPG signals, we extracted features in a total of 30 dimensions from time-domain, frequency-domain, and wavelet packet decomposition. Logistic regression, support vector regression, random forest, and XGBoost regression models were established to achieve hemorrhagic risk evaluation, and then, their performances were compared. In total, 10 features extracted from PPG showed statistical significance (p < 0.01) between negative and positive groups. The newly established XGBoost model performed best in the hemorrhagic risk evaluation experiment, wherein the mean area under the curve (AUC) with tenfold cross-validation was 0.762 ± 0.024 and the sensitivity and specificity were 0.679 ± 0.051 and 0.714 ± 0.014, respectively. We established a data acquisition system for PPG signal collection, and demonstrated that a set of features extracted from PPG and the proposed machine learning model are promising in the evaluation of hemorrhagic risk among patients with CAD. In comparison with the traditional HAS-BLED score, the proposed method can obtain the quantitative risk prediction probability from a single PPG record, which has the advantages of dynamics and continuity, and can provide timely feedback for doctors' antithrombotic treatment, which is of great significance for doctors to quickly determine the effectiveness of the treatment and adjust the timely treatment plans accordingly.
Thirty percent conversion efficiency from radiofrequency power to thrust energy in a magnetic nozzle plasma thruster
Authors: Takahashi Kazunori
Published: November 2022

Innovations for terrestrial transportation technologies, e.g., cars, aircraft, and so on, have driven historical industries so far, and a similar breakthrough is now occurring in space owing to the successful development of electric propulsion devices such as gridded ion and Hall effect thrusters, where solar power is converted into the momentum of the propellant via acceleration of the ionized gases, resulting in a high specific impulse. A magnetic nozzle (MN) radiofrequency (rf) plasma thruster consisting of a low-pressure rf plasma source and a MN is an attractive candidate for a high-power electric propulsion device for spacecraft, as it will provide a long lifetime operation at a high-power level due to the absence of an electrode exposed to the plasma and a high thrust density. The high-density plasma produced in the source is transported along the magnetic field lines toward the open-source exit and the plasma is then spontaneously accelerated in the MN. By ejecting the plasma flow from the system, the reaction forces are exerted to the thruster structure including the source and the MN, and the spacecraft is resultantly propelled. The thruster will open the next door for space technologies, while the performance of the MN rf plasma thruster has been lower than those of the mature electric propulsion devices due to the energy loss to the physical walls. Here the thruster efficiency of about 30%, being the highest to date in this type of thruster, is successfully obtained in the MN rf plasma thruster by locating a cusp magnetic field inside the source, which acts as a virtual magnetic wall isolating the plasma from the source wall. The increase in the thrust by the cusp can be explained by considering the reductions of the loss area and the plasma volume in a thrust analysis combining a global source model and a one-dimensional MN model.
Rosa26-LSL-dCas9-VPR: a versatile mouse model for tissue specific and simultaneous activation of multiple genes for drug discovery
Authors: Pakalniškytė Dalia , Schönberger Tanja , Strobel Benjamin , Stierstorfer Birgit , Lamla Thorsten , Schuler Michael , Lenter Martin
Published: November 2022

Transgenic animals with increased or abrogated target gene expression are powerful tools for drug discovery research. Here, we developed a CRISPR-based Rosa26-LSL-dCas9-VPR mouse model for targeted induction of endogenous gene expression using different Adeno-associated virus (AAV) capsid variants for tissue-specific gRNAs delivery. To show applicability of the model, we targeted low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9), either individually or together. We induced up to ninefold higher expression of hepatocellular proteins. In consequence of LDLR upregulation, plasma LDL levels almost abolished, whereas upregulation of PCSK9 led to increased plasma LDL and cholesterol levels. Strikingly, simultaneous upregulation of both LDLR and PCSK9 resulted in almost unaltered LDL levels. Additionally, we used our model to achieve expression of all α1-Antitrypsin (AAT) gene paralogues simultaneously. These results show the potential of our model as a versatile tool for optimized targeted gene expression, alone or in combination.
Testing the effects of perceptual grouping on visual search in older adults
Authors: Jingling Li , Lai Sung-Nan
Published: November 2022

Visual search is to find targets while ignoring distractors. Previous studies established that a target is more difficult to identify if aligned collinearly with other items, called the collinear search impairment. Since older adults have lower perceptual grouping ability than younger adults, benefits in visual search may occur for older adults for they may be less distracted by the collinear distractors. Three experiments were carried out to compare 45 younger and 45 older healthy adults. Participants were asked to identify a local target either in the column with items collinearly aligned to each other (the overlapping condition) or in the background (the non-overlapping condition), and the response difference between the two conditions is the collinear search impairment. Results showed that both groups showed reliable search impairment specific to collinear distractor regardless of grouping difficulty and task demands, and the impairment strength increased with the grouping strength of the collinear distractor. Further analysis revealed that the response times of older adults increased in a multiplicative manner to that of younger adults, suggesting that longer response of older adults spread to multiple underlying processing including grouping and suppression of collinear distractors. Together, the results suggest that older adults were still distracted in visual search even when grouping was required on a distractor. Our findings also highlight how general slowing may delay suppression processing in visual search.
Deep learning signature of brain [18F]FDG PET associated with cognitive outcome of rapid eye movement sleep behavior disorder
Authors: Ryoo Hyun Gee , Byun Jung-Ick , Choi Hongyoon , Jung Ki-Young
Published: November 2022

An objective biomarker to predict the outcome of isolated rapid eye movement sleep behavior disorder (iRBD) is crucial for the management. This study aimed to investigate cognitive signature of brain [18F]FDG PET based on deep learning (DL) for evaluating patients with iRBD. Fifty iRBD patients, 19 with mild cognitive impairment (MCI) (RBD-MCI) and 31 without MCI (RBD-nonMCI), were prospectively enrolled. A DL model for the cognitive signature was trained by using Alzheimer’s Disease Neuroimaging Initiative database and transferred to baseline [18F]FDG PET from the iRBD cohort. The results showed that the DL-based cognitive dysfunction score was significantly higher in RBD-MCI than in RBD-nonMCI. The AUC of ROC curve for differentiating RBD-MCI from RBD-nonMCI was 0.70 (95% CI 0.56–0.82). The baseline DL-based cognitive dysfunction score was significantly higher in iRBD patients who showed a decrease in CERAD scores during 2 years than in those who did not. Brain metabolic features related to cognitive dysfunction-related regions of individual iRBD patients mainly included posterior cortical regions. This work demonstrates that the cognitive signature based on DL could be used to objectively evaluate cognitive function in iRBD. We suggest that this approach could be extended to an objective biomarker predicting cognitive decline and neurodegeneration in iRBD.
Large studies reveal how reference bias limits policy applications of self-report measures
Authors: Lira Benjamin , O’Brien Joseph M. , Peña Pablo A. , Galla Brian M. , D’Mello Sidney , Yeager David S. , Defnet Amy , Kautz Tim , Munkacsy Kate , Duckworth Angela L.
Published: November 2022

There is growing policy interest in identifying contexts that cultivate self-regulation. Doing so often entails comparing groups of individuals (e.g., from different schools). We show that self-report questionnaires—the most prevalent modality for assessing self-regulation—are prone to reference bias, defined as systematic error arising from differences in the implicit standards by which individuals evaluate behavior. In three studies, adolescents (N = 229,685) whose peers performed better academically rated themselves lower in self-regulation and held higher standards for self-regulation. This effect was not observed for task measures of self-regulation and led to paradoxical predictions of college persistence 6 years later. These findings suggest that standards for self-regulation vary by social group, limiting the policy applications of self-report questionnaires.
Effect of the sagittal osteotomy inclination angle on the posterior tibial slope change in high tibial osteotomy: three-dimensional simulation study
Authors: Chung Jai Hyun , Choi Chong Hyuk , Kim Sung-Hwan , Kim Sung-Jae , Suk Yong June , Jung Min
Published: November 2022

In performing medial open-wedge high tibial osteotomy, it is recommended not to alter the posterior tibial slope. However, it remains unclear whether the osteotomy inclination angle affects the posterior tibial slope in the sagittal plane. This study aimed to verify how anterior or posterior osteotomy inclination angle affects the tendency of change in the posterior tibial slope and to conduct quantitative analysis of the extent to which the posterior tibial slope changes according to the degree of the osteotomy inclination angle change in MOWHTO. Computed tomography images of 30 patients who underwent MOWHTO were collected. Three-dimensional models of preoperative original tibia were reconstructed, and virtual osteotomies were performed. The sagittal osteotomy inclination angles formed by the osteotomy line and the medial tibial plateau line were classified as positive in case of anteriorly inclined osteotomy and negative in case of posteriorly inclined osteotomy. Thirteen osteotomies were performed for each tibial model at intervals of 5° from − 30° to 30°. The posterior tibial slope was assessed, and the proportional relationship between the sagittal osteotomy inclination angle and the posterior tibial slope change was analyzed. The posterior tibial slope changed significantly after osteotomy (p < 0.001), except for the cases where the sagittal osteotomy inclination angles were 5°, 0°, and − 5°. Anteriorly and posteriorly inclined osteotomy caused increase and decrease in the posterior tibial slope, respectively. As the inclination angle increased by 1°, the posterior tibial slope increased by 0.079° in anterior inclination osteotomy, while in posterior inclination osteotomy, as the inclination angle decreased by 1°, the posterior tibial slope decreased by 0.067°. The osteotomy inclination angle in the sagittal plane significantly affected the posterior tibial slope. When there was an inclination angle occurred between the osteotomy line and the medial tibial plateau line in the sagittal plane, the posterior tibial slope changed after MOWHTO. The posterior tibial slope tended to increase in anteriorly inclined osteotomy and decrease in posteriorly inclined osteotomy. The change in the posterior tibial slope was proportionally related to the absolute value of the osteotomy inclination angle.
Real-world clinical effectiveness and sustainability of universal bloodborne virus testing in an urban emergency department in the UK
Authors: Smout Elizabeth , Phyu Khine , Hughes Gareth J. , Parker Lee , Rezai Roozbeh , Evans Amy , McLaren Joscelyne , Bush Stephen , Davey Sarah , Aldersley Mark A. , Ruf Murad , Page Emma E.
Published: November 2022

Innovative testing approaches and care pathways are required to meet HIV, hepatitis B (HBV) and hepatitis C (HCV) elimination goals. Routine testing for blood-borne viruses (BBVs) within emergency departments (EDs) is suggested by the European Centre for Disease Prevention and Control but there is a paucity of supporting evidence. We evaluated the introduction of routine BBV testing in EDs at a large teaching hospital in northern England. In October 2018, we modified the electronic laboratory ordering system to reflex opt-out HIV, HBV and HCV testing for all ED attendees aged 16–65 years who had a routine blood test for urea and electrolytes (U&Es). Linkage to care (LTC) was attempted for newly diagnosed patients, those never referred and those who had previously disengaged from care. The project operated for 18 months, here we present evaluation of the initial nine months (2 October 2018–1 July 2019). We analysed testing uptake, BBV seropositivity, LTC and treatment initiation within six months post-diagnosis. Over 9 months, 17,026/28,178 (60.4%) ED attendees who had U&Es performed were tested for ≥ 1 BBV. 299 active BBV infections were identified: 70 HIV Ab/Ag-positive (0.4% seroprevalence), 73 HBsAg-positive (0.4%) and 156 HCV RNA-positive (1.0%). Only 24.3% (17/70) HIV Ab/Ag-positive individuals required LTC, compared to 94.9% (148/156) HCV RNA-positive and 53.4% (39/73) HBsAg-positive individuals. LTC was successful in 94.1% (16/17) HIV Ab/Ag-positive and 69.3% (27/39) HBsAg-positive individuals. However, at 6 months LTC was just 39.2% (58/148) for HCV RNA-positive individuals, with 64% (37/58) of these commencing treatment. Universal opt-out ED BBV testing proved feasible and effective in identifying active BBV infections, especially among marginalised populations with reduced healthcare access. Our integrated approach achieved good LTC rates although further service development is necessary, particularly for HCV RNA-positive people who inject drugs.