bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence-Based Policy Making during the Coronavirus Disease 2019 Pandemic: A Systematic Review
Authors: Matsuda Shinpei , Yoshimura Hitoshi
Published: March 2023

Introduction:

The aim of this systematic review was to collect evidence and recommendations for the applicability of the concept of evidence-based policy making (EBPM) during the coronavirus disease 2019 (COVID-19) pandemic and to discuss the implementation of this concept from a medical science perspective.

Methods:

This study was performed according to the guidelines, checklist, and flow diagram of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. An electronic literature search was conducted on September 20, 2022 using PubMed, Web of Science, Cochrane Library, and CINAHL databases with the following search terms: “evidence based policy making” and “infectious disease.” Study eligibility assessment was performed based on the flow diagram of PRISMA 2020, and risk of bias assessment was performed using The Critical Appraisal Skills Program.

Results:

Eleven eligible articles were included in this review and divided into three groups as follows: early, middle, and late stages of the COVID-19 pandemic. Basics of COVID-19 control were suggested in the early stage. The articles published in the middle stage discussed the importance of the collection and analysis of evidence of COVID-19 from around the world for the establishment of EBPM in the COVID-19 pandemic. The articles published in the late stage discussed the collection of large amounts of high-quality data and the development of methods to analyze them, as well as emerging issues related to the COVID-19 pandemic.

Conclusions:

This study revealed that the concept of EBPM applicable to emerging infectious disease pandemics changed between the early, middle, and late stages of the pandemic. The concept of EBPM will play an important role in medicine in the future.
Using Machine Learning to Cut the Cost of Dynamical Downscaling
Authors: Hobeichi Sanaa , Nishant Nidhi , Shao Yawen , Abramowitz Gab , Pitman Andy , Sherwood Steve , Bishop Craig , Green Samuel
Published: March 2023

Global climate models (GCMs) are commonly downscaled to understand future local climate change. The high computational cost of regional climate models (RCMs) limits how many GCMs can be dynamically downscaled, restricting uncertainty assessment. While statistical downscaling is cheaper, its validity in a changing climate is unclear. We combine these approaches to build an emulator leveraging the merits of dynamical and statistical downscaling. A machine learning model is developed for each coarse grid cell to predict fine grid variables, using coarse‐scale climate predictors with fine grid land characteristics. Two RCM emulators, one Multilayer Perceptron (MLP) and one Multiple Linear Regression error‐reduced with Random Forest (MLR‐RF), are developed to downscale daily evapotranspiration from 12.5 km (coarse‐scale) to 1.5 km (fine‐scale). Out‐of‐sample tests for the MLP and MLR‐RF achieve Kling‐Gupta‐Efficiency of 0.86 and 0.83, correlation of 0.89 and 0.86, and coefficient of determination (R2) of 0.78 and 0.75, with a relative bias of −6% to 5% and −5% to 4%, respectively. Using histogram match for spatial efficiency, both emulators achieve a median score of ∼0.77. This is generally better than a common statistical downscaling method in a range of metrics. Additionally, through “spatial transitivity,” we can downscale GCMs for new regions at negligible cost and only minor performance loss. The framework offers a cheap and quick way to downscale large ensembles of GCMs. This could enable high‐resolution climate projections from a larger number of global models, enabling uncertainty quantification, and so better support for resilience and adaptation planning.
Decadal Changes in Ventilation and Anthropogenic Carbon in the Nordic Seas
Authors: Jeansson Emil , Tanhua Toste , Olsen Are , Smethie William M. , Rajasakaren Balamuralli , Ólafsdóttir Sólveig R. , Ólafsson Jón
Published: March 2023

We evaluate the decadal evolution of ventilation and anthropogenic carbon (Cant) in the Nordic Seas between 1982 and the 2010s. Ventilation changes on decadal timescale are identified by evaluating decadal changes in mean ages and apparent oxygen utilization in each of the four main basins of the Nordic Seas (the Greenland and Iceland Seas, and the Norwegian and Lofoten Basins). The ages are derived from the transient time distribution approach, based on the transient tracers chlorofluorocarbon‐12 (CFC‐12) and sulfur hexafluoride (SF6). The different decades show different phases in ventilation, with the 2000s being overall better ventilated than the 1990s in all basins. For the Greenland Sea, we also show that the 2010s are better ventilated than the 2000s, with a clear shift in hydrographic properties. The evolution of concentrations and inventory of Cant is linked to the ventilation state. The deep waters get progressively older over the analyzed period, which is connected to the increased fraction of deep water from the Arctic Ocean.
Regime‐Specific Cloud Vertical Overlap Characteristics From Radar and Lidar Observations at the ARM Sites
Authors: Balmes Kelly A. , Sedlar Joseph , Riihimaki Laura D. , Olson Joseph B. , Turner David D. , Lantz Kathleen
Published: March 2023

Climate and numerical weather prediction models require assumptions to represent the vertical distribution of subgrid‐scale clouds, which have radiative transfer implications. In this study, nearly 25 years of ground‐based radar and lidar observations of vertical cloud profiles at the Atmospheric Radiation Measurement Program (ARM) Southern Great Plains (SGP) site are utilized to derive cloud vertical overlap characteristics from the Cloud Type (CLDTYPE) data product. The cloud vertical overlap characteristics are further separated by cloud regime by considering seven cloud types (i.e., low cloud, congestus, deep convection, altocumulus, altostratus, cirrostratus, and cirrus) as well as periods of shallow cumulus. The decorrelation length scale (i.e., exponential transition from maximum to random overlap with layer separation) is found to vary by cloud regime, ranging between 0.04 km for cirrostratus paired with cirrus to 4.58 km for low cloud paired with cirrus at SGP. Cloud vertical overlap characteristics are also considered for other ARM sites including the Tropical Western Pacific (TWP), North Slope of Alaska (NSA), and Eastern North Atlantic (ENA) sites among other shorter term ARM deployments globally. The decorrelation length scale ranged globally from 1.03 km in the Arctic Ocean to 3.06 km in Manacapuru, Brazil. Globally, the decorrelation length scale by cloud regime exhibited similarities (e.g., for cirrus paired with cirrus) and differences (e.g., congestus paired with cirrus). The results could help inform development of cloud vertical overlap assumptions within operational numerical weather prediction models and potentially improve prediction of radiative fluxes for weather, climate, and renewable energy forecasting.
Formation Mechanisms and Source Apportionments of Nitrate Aerosols in a Megacity of Eastern China Based On Multiple Isotope Observations
Authors: Fan Mei‐Yi , Zhang Wenqi , Zhang Yan‐Lin , Li Jianghanyang , Fang Huan , Cao Fang , Yan Ming , Hong Yihang , Guo Hai , Michalski Greg
Published: March 2023

Inorganic nitrate (NO3−) is a crucial component of fine particulate matter (PM2.5) in haze events in China. Understanding the formation mechanisms of nitrate and the sources of NOx was critical to control the air pollution. In this study, measurements of multiple isotope compositions of nitrate (δ18O‐NO3−, δ17O‐NO3−, and δ15N‐NO3−) in PM2.5 were conducted in Hangzhou from 9 October 2015 to 24 August 2016. Our results showed that oxygen anomaly of nitrate (Δ17O‐NO3−: 20.0‰–37.9‰) and nitrogen isotope of nitrate (δ15N‐NO3−: −2.9‰ to 18.1‰) values were higher in winter and lower in summer. Based on Δ17O‐NO3− observation and a Bayesian model, NO3 radical chemistry was found to dominate the nitrate formation in winter, while photochemical reaction (NO2 + OH) was the main pathway in summer. After considering the nitrogen isotopic fractionation in the NOx(g)‐NO3−(p) conversion, the average contributions of coal combustion, vehicle exhausts, biomass burning, and soil emission were 50% ± 9%, 19% ± 12%, 26% ± 15%, and 5% ± 4%, respectively, to nitrate aerosols during the whole sampling period. Coal combustion was the most important nitrate source in Hangzhou, especially in winter (∼56%). The contribution of soil emission increased significantly in summer due to active soil microbial processes under high temperature environment.
Interactions Between Depositional Regime and Climate Proxies in the Northern South China Sea Since the Last Glacial Maximum
Authors: Wang Xuesong , Zhong Yi , Clift Peter D. , Feng Yingci , Wilson David J. , Kaboth‐Bahr Stefanie , Bahr André , Gong Xun , Zhao Debo , Chen Zhong , Zhang Yanan , Tian Yuhang , Liu Yuxing , Liu Xiaoyu , Liu Jiabo , Xia Wenyue , Yang Huihui , Cao Wei , Liu Qingsong
Published: March 2023

Sedimentary deposits from the northern South China Sea (SCS) can provide important constraints on past changes in ocean currents and the East Asian summer monsoon (EASM) in this region. However, the interpretation of such records spanning the last deglaciation is complicated because sea‐level change may also have influenced the depositional processes and patterns. Here, we present new records of grain size, clay mineralogy, and magnetic mineralogy spanning the past 24 kyr from both shallow and deep‐water sediment cores in the northern SCS. Our multi‐proxy comparison among multiple cores helps constrain the influence of sea‐level change, providing confidence in interpreting the regional climate‐forced signals. After accounting for the influence of sea‐level change, we find that these multi‐proxy records reflect a combination of changes in (a) the strength of the North Pacific Intermediate Water inflow, (b) the EASM strength, and (c) the Kuroshio Current extent. Overall, this study provides new insights into the roles of varying terrestrial weathering and oceanographic processes in controlling the depositional record on the northern SCS margin in response to climate and sea‐level fluctuations.
High Energy Solar Particle Events and Their Relationship to Associated Flare, CME and GLE Parameters
Authors: Waterfall C. O. G. , Dalla S. , Raukunen O. , Heynderickx D. , Jiggens P. , Vainio R.
Published: March 2023

Large solar eruptive events, including solar flares and coronal mass ejections (CMEs), can lead to solar energetic particle (SEP) events. During these events, protons are accelerated up to several GeV and pose numerous space weather risks. These risks include, but are not limited to, radiation hazards to astronauts and disruption to satellites and electronics. The highest energy SEPs are capable of reaching Earth on timescales of minutes and can be detected in ground level enhancements (GLEs). Understanding and analyzing these events is critical to future forecasting models. However, the availability of high energy SEP data sets is limited, especially that which covers multiple solar cycles. The majority of analysis of SEP events considers data at energies <100 MeV. In this work, we use a newly calibrated data set using data from Geostationary Operational Environmental Satellite‐high energy proton and alpha detector between 1984 and 2017. Analysis of the SEP events in this time period over three high energy channels is performed, and SEP properties are compared to flare and CME parameters. In addition, neutron monitor (NM) observations are examined for the relevant GLE events. We find that correlations between SEP peak intensity and the CME speed are much weaker than for lower SEP energies. Correlations with flare intensity are broadly similar or weaker. Strong correlations are seen between >300 MeV data and GLE properties from NM data. The results of our work can be utilized in future forecasting models for both high energy SEP and GLE events.
Breaking the resolution-bandwidth limit of chip-scale spectrometry by harnessing a dispersion-engineered photonic molecule
Authors: Xu Hongnan , Qin Yue , Hu Gaolei , Tsang Hon Ki
Published: March 2023

The chip-scale integration of optical spectrometers may offer new opportunities for in situ bio-chemical analysis, remote sensing, and intelligent health care. The miniaturization of integrated spectrometers faces the challenge of an inherent trade-off between spectral resolutions and working bandwidths. Typically, a high resolution requires long optical paths, which in turn reduces the free-spectral range (FSR). In this paper, we propose and demonstrate a ground-breaking spectrometer design beyond the resolution-bandwidth limit. We tailor the dispersion of mode splitting in a photonic molecule to identify the spectral information at different FSRs. When tuning over a single FSR, each wavelength channel is encoded with a unique scanning trace, which enables the decorrelation over the whole bandwidth spanning multiple FSRs. Fourier analysis reveals that each left singular vector of the transmission matrix is mapped to a unique frequency component of the recorded output signal with a high sideband suppression ratio. Thus, unknown input spectra can be retrieved by solving a linear inverse problem with iterative optimizations. Experimental results demonstrate that this approach can resolve any arbitrary spectra with discrete, continuous, or hybrid features. An ultrahigh resolution of <40 pm is achieved throughout an ultrabroad bandwidth of >100 nm far exceeding the narrow FSR. An ultralarge wavelength-channel capacity of 2501 is supported by a single spatial channel within an ultrasmall footprint (≈60 × 60 μm2), which represents, to the best of our knowledge, the highest channel-to-footprint ratio (≈0.69 μm−2) and spectral-to-spatial ratio (>2501) ever demonstrated to date.
Erianin suppresses constitutive activation of MAPK signaling pathway by inhibition of CRAF and MEK1/2
Authors: Wang Penglei , Jia Xuechao , Lu Bingbing , Huang Han , Liu Jialin , Liu Xuejiao , Wu Qiong , Hu Yamei , Li Pan , Wei Huifang , Liu Tingting , Zhao Dengyun , Zhang Lingwei , Tian Xueli , Jiang Yanan , Qiao Yan , Nie Wenna , Ma Xinli , Bai Ruihua , Peng Cong , Dong Zigang , Liu Kangdong
Published: March 2023

Constitutive activation of RAS-RAF-MEK-ERK signaling pathway (MAPK pathway) frequently occurs in many cancers harboring RAS or RAF oncogenic mutations. Because of the paradoxical activation induced by a single use of BRAF or MEK inhibitors, dual-target RAF and MEK treatment is thought to be a promising strategy. In this work, we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases, thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS mutations. KinaseProfiler enzyme profiling, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), cellular thermal shift assay, computational docking, and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/2. Kinase assay, luminescent ADP detection assay, and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase activity. Notably, erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase activity. Moreover, erianin attenuated melanoma and colorectal cancer in vivo. Overall, we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2.
ACx-projecting cholinergic neurons in the NB influence the BLA ensembles to modulate the discrimination of auditory fear memory
Authors: Yan Yan , Song Da , Jin Yue , Deng Yujun , Wang Chunjian , Huang Tao , Tang Yuanhong , Yang Yu , Zhang Yun , Wang Zhe , Dong Zhifang , Wang Yuetian , Zhao Juan , Ni Junjun , Li Hui , Zhang Jun , Lang Yiran , Wu Yili , Qing Hong , Quan Zhenzhen
Published: March 2023

Animals need discriminating auditory fear memory (DAFM) to survive, but the related neural circuits of DAFM remain largely unknown. Our study shows that DAFM depends on acetylcholine (ACh) signal in the auditory cortex (ACx), which is projected from the nucleus basalis (NB). At the encoding stage, optogenetic inhibition of cholinergic projections of NB-ACx obfuscates distinct tone-responsive neurons of ACx recognizing from fear-paired tone to fear-unpaired tone signals, while simultaneously regulating the neuronal activity and reactivation of basal lateral amygdala (BLA) engram cells at the retrieval stage. This NBACh-ACx-BLA neural circuit for the modulation of DAFM is especially dependent on the nicotinic ACh receptor (nAChR). A nAChR antagonist reduces DAFM and diminishes the increased magnitude of ACx tone-responsive neuronal activity during the encoding stage. Our data suggest a critical role of NBACh-ACx-BLA neural circuit in DAFM: manipulation of the NB cholinergic projection to the ACx via nAChR during the encoding stage affects the activation of ACx tone-responsive neuron clusters and the BLA engram cells during the retrieval stage, thus modulating the DAFM.
TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1
Authors: Wang Xiaobo , Shi Jiawei , Huang Mingming , Chen Jiehong , Dan Jia , Tang Yunhua , Guo Zhiyong , He Xiaoshun , Zhao Qiang
Published: March 2023

Cholesterol metabolism plays a critical role in the progression of hepatocellular carcinoma (HCC), but it is not clear how cholesterol metabolism is regulated. The tubulin beta class I genes (TUBBs) are associated with the prognosis of many different cancers. To confirm the function of TUBBs in HCC, the Kaplan–Meier method and Cox analyses were performed using TCGA and GSE14520 datasets. A higher expression of TUBB2B is an independent prognostic factor for shorter over survival in HCC patients. Deletion of TUBB2B in hepatocytes inhibits proliferation and promotes tumor cell apoptosis, while over-expression of TUBB2B has the opposite function. This result was confirmed in a mouse xenograft tumor model. Mechanistically, TUBB2B induces the expression of CYP27A1, an enzyme responsible for the conversion of cholesterol to 27-hydroxycholesterol, which leads to the up-regulation of cholesterol and the progression of HCC. In addition, TUBB2B regulates CYP27A1 via human hepatocyte nuclear factor 4alpha (HNF4A). These findings indicated that TUBB2B functions as an oncogene in HCC, and plays a role in promoting cell proliferation and anti-apoptosis through targeting HNF4A/CYP27A1/cholesterol.
Tunable hybrid zeolites prepared by partial interconversion
Authors: Mendoza-Castro Monica J. , Qie Zhipeng , Fan Xiaolei , Linares Noemi , García-Martínez Javier
Published: March 2023

Zeolite interconversion is a widely used strategy due to its unique advantages in the synthesis of some zeolites. By using a long-chain quaternary amine as both a structure-directing agent and porogen, we have produced superior catalysts, which we named Hybrid Zeolites, as their structures are made of building units of different zeolite types. The properties of these materials can be conveniently tuned, and their catalytic performance can be optimized simply by stopping the interconversion at different times. For cracking the 1,3,5-triisopropylbenzene, Hybrid Zeolites made of FAU and MFI units show a 5-fold increase in selectivity towards the desired product, that is, 1,3-diisopropylbenzene, compared to the commercial FAU, and a 7-fold increase in conversion at constant selectivity compared to MFI zeolite.
Mucociliary Wnt signaling promotes cilia biogenesis and beating
Authors: Seidl Carina , Da Silva Fabio , Zhang Kaiqing , Wohlgemuth Kai , Omran Heymut , Niehrs Christof
Published: March 2023

It is widely thought that Wnt/Lrp6 signaling proceeds through the cytoplasm and that motile cilia are signaling-inert nanomotors. Contrasting both views, we here show in the mucociliary epidermis ofX. tropicalisembryos that motile cilia transduce a ciliary Wnt signal that is distinct from canonical β-catenin signaling. Instead, it engages a Wnt-Gsk3-Ppp1r11-Pp1 signaling axis. Mucociliary Wnt signaling is essential for ciliogenesis and it engages Lrp6 co-receptors that localize to cilia via a VxP ciliary targeting sequence. Live-cell imaging using a ciliary Gsk3 biosensor reveals an immediate response of motile cilia to Wnt ligand. Wnt treatment stimulates ciliary beating inX. tropicalisembryos and primary human airway mucociliary epithelia. Moreover, Wnt treatment improves ciliary function inX. tropicalisciliopathy models of male infertility and primary ciliary dyskinesia (ccdc108,gas2l2). We conclude thatX. tropicalismotile cilia are Wnt signaling organelles that transduce a distinct Wnt-Pp1 response.
Ultrafast motion in a third generation photomolecular motor
Authors: Roy Palas , Browne Wesley R. , Feringa Ben L. , Meech Stephen R.
Published: March 2023

Controlling molecular translation at the nanoscale is a key objective for development of synthetic molecular machines. Recently developed third generation photochemically driven molecular motors (3GMs), comprising pairs of overcrowded alkenes capable of cooperative unidirectional rotation offer the possibility of converting light energy into translational motion. Further development of 3GMs demands detailed understanding of their excited state dynamics. Here we use time-resolved absorption and emission to track population and coherence dynamics in a 3GM. Femtosecond stimulated Raman reveals real-time structural dynamics as the excited state evolves from a Franck-Condon bright-state through weakly-emissive dark-state to the metastable product, yielding new insight into the reaction coordinate. Solvent polarity modifies the photoconversion efficiency suggesting charge transfer character in the dark-state. The enhanced quantum yield correlates with suppression of a low-frequency flapping motion in the excited state. This detailed characterization facilitates development of 3GMs, suggesting exploitation of medium and substituent effects to modulate motor efficiency.
Localizing strain via micro-cage structure for stretchable pressure sensor arrays with ultralow spatial crosstalk
Authors: Zhang Yufei , Lu Qiuchun , He Jiang , Huo Zhihao , Zhou Runhui , Han Xun , Jia Mengmeng , Pan Caofeng , Wang Zhong Lin , Zhai Junyi
Published: March 2023

Tactile sensors with high spatial resolution are crucial to manufacture large scale flexible electronics, and low crosstalk sensor array combined with advanced data analysis is beneficial to improve detection accuracy. Here, we demonstrated the photo-reticulated strain localization films (prslPDMS) to prepare the ultralow crosstalk sensor array, which form a micro-cage structure to reduce the pixel deformation overflow by 90.3% compared to that of conventional flexible electronics. It is worth noting that prslPDMS acts as an adhesion layer and provide spacer for pressure sensing. Hence, the sensor achieves the sufficient pressure resolution to detect 1 g weight even in bending condition, and it could monitor human pulse under different states or analyze the grasping postures. Experiments show that the sensor array acquires clear pressure imaging and ultralow crosstalk (33.41 dB) without complicated data processing, indicating that it has a broad application prospect in precise tactile detection.
High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding
Authors: Zhong Jia-Yong , Niu Longjian , Lin Zhuo-Bin , Bai Xin , Chen Ying , Luo Feng , Hou Chunhui , Xiao Chuan-Le
Published: March 2023

Canonical three-dimensional (3D) genome structures represent the ensemble average of pairwise chromatin interactions but not the single-allele topologies in populations of cells. Recently developed Pore-C can capture multiway chromatin contacts that reflect regional topologies of single chromosomes. By carrying out high-throughput Pore-C, we reveal extensive but regionally restricted clusters of single-allele topologies that aggregate into canonical 3D genome structures in two human cell types. We show that fragments in multi-contact reads generally coexist in the same TAD. In contrast, a concurrent significant proportion of multi-contact reads span multiple compartments of the same chromatin type over megabase distances. Synergistic chromatin looping between multiple sites in multi-contact reads is rare compared to pairwise interactions. Interestingly, the single-allele topology clusters are cell type-specific even inside highly conserved TADs in different types of cells. In summary, HiPore-C enables global characterization of single-allele topologies at an unprecedented depth to reveal elusive genome folding principles.
Minimal non-abelian nodal braiding in ideal metamaterials
Authors: Qiu Huahui , Zhang Qicheng , Liu Tingzhi , Fan Xiying , Zhang Fan , Qiu Chunyin
Published: March 2023

Exploring new topological phases and phenomena has become a vital topic in condensed matter physics and materials sciences. Recent studies reveal that a braided colliding nodal pair can be stabilized in a multi-gap system with $$PT$$
P
T
or $${C}_{2z}T$$

C

2
z

T
symmetry. This exemplifies non-abelian topological charges beyond the scope of conventional single-gap abelian band topology. Here, we construct ideal acoustic metamaterials to realize non-abelian braiding with the fewest band nodes. By emulating the time with a sequence of acoustic samples, we experimentally observe an elegant but nontrivial nodal braiding process, including nodes creation, braiding, collision, and repulsion (i.e., impossible to annihilate), and measure the mirror eigenvalues to elucidate the braiding consequence. The latter, at the level of wavefunctions, is of prime importance since essentially braiding physics aims to entangle multi-band wavefunctions. Furthermore, we experimentally unveil the highly intricate correlation between the multi-gap edge responses and the bulk non-abelian charges. Our findings pave the way for developing non-abelian topological physics that is still in its infancy.
ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease
Authors: Stecklein Shane R. , Kimler Bruce F. , Yoder Rachel , Schwensen Kelsey , Staley Joshua M. , Khan Qamar J. , O’Dea Anne P. , Nye Lauren E. , Elia Manana , Heldstab Jaimie , Home Trisha , Hyter Stephen , Isakova Kamilla , Pathak Harsh B. , Godwin Andrew K. , Sharma Priyanka
Published: March 2023

Triple-negative breast cancer (TNBC) patients with residual disease (RD) after neoadjuvant systemic therapy (NAST) are at high risk for recurrence. Biomarkers to risk-stratify patients with RD could help individualize adjuvant therapy and inform future adjuvant therapy trials. We aim to investigate the impact of circulating tumor DNA (ctDNA) status and residual cancer burden (RCB) class on outcomes in TNBC patients with RD. We analyze end-of-treatment ctDNA status in 80 TNBC patients with residual disease who are enrolled in a prospective multisite registry. Among 80 patients, 33% are ctDNA positive (ctDNA+) and RCB class distribution is RCB-I = 26%, RCB-II = 49%, RCB-III = 18% and 7% unknown. ctDNA status is associated with RCB status, with 14%, 31%, and 57% of patients within RCB-I, -II, and -III classes demonstrating ctDNA+ status (P = 0.028). ctDNA+ status is associated with inferior 3-year EFS (48% vs. 82%, P < 0.001) and OS (50% vs. 86%, P = 0.002). ctDNA+ status predicts inferior 3-year EFS among RCB-II patients (65% vs. 87%, P = 0.044) and shows a trend for inferior EFS among RCB-III patients (13% vs. 40%, P = 0.081). On multivariate analysis accounting for T stage and nodal status, RCB class and ctDNA status independently predict EFS (HR = 5.16, P = 0.016 for RCB class; HR = 3.71, P = 0.020 for ctDNA status). End-of-treatment ctDNA is detectable in one-third of TNBC patients with residual disease after NAST. ctDNA status and RCB are independently prognostic in this setting.
Uncertainty-aware molecular dynamics from Bayesian active learning for phase transformations and thermal transport in SiC
Authors: Xie Yu , Vandermause Jonathan , Ramakers Senja , Protik Nakib H. , Johansson Anders , Kozinsky Boris
Published: March 2023

Machine learning interatomic force fields are promising for combining high computational efficiency and accuracy in modeling quantum interactions and simulating atomistic dynamics. Active learning methods have been recently developed to train force fields efficiently and automatically. Among them, Bayesian active learning utilizes principled uncertainty quantification to make data acquisition decisions. In this work, we present a general Bayesian active learning workflow, where the force field is constructed from a sparse Gaussian process regression model based on atomic cluster expansion descriptors. To circumvent the high computational cost of the sparse Gaussian process uncertainty calculation, we formulate a high-performance approximate mapping of the uncertainty and demonstrate a speedup of several orders of magnitude. We demonstrate the autonomous active learning workflow by training a Bayesian force field model for silicon carbide (SiC) polymorphs in only a few days of computer time and show that pressure-induced phase transformations are accurately captured. The resulting model exhibits close agreement with both ab initio calculations and experimental measurements, and outperforms existing empirical models on vibrational and thermal properties. The active learning workflow readily generalizes to a wide range of material systems and accelerates their computational understanding.
ATM signaling modulates cohesin behavior in meiotic prophase and proliferating cells
Authors: Yu Zhouliang , Kim Hyung Jun , Dernburg Abby F.
Published: March 2023

Cohesins are ancient and ubiquitous regulators of chromosome architecture and function, but their diverse roles and regulation remain poorly understood. During meiosis, chromosomes are reorganized as linear arrays of chromatin loops around a cohesin axis. This unique organization underlies homolog pairing, synapsis, double-stranded break induction, and recombination. We report that axis assembly inCaenorhabditiselegansis promoted by DNA-damage response (DDR) kinases that are activated at meiotic entry, even in the absence of DNA breaks. Downregulation of the cohesin-destabilizing factor WAPL-1 by ATM-1 promotes axis association of cohesins containing the meiotic kleisins COH-3 and COH-4. ECO-1 and PDS-5 also contribute to stabilizing axis-associated meiotic cohesins. Further, our data suggest that cohesin-enriched domains that promote DNA repair in mammalian cells also depend on WAPL inhibition by ATM. Thus, DDR and Wapl seem to play conserved roles in cohesin regulation in meiotic prophase and proliferating cells.
Antigenotoxic properties of the halophyte Polygonum maritimum L. highlight its potential to mitigate oxidative stress-related damage
Authors: Oliveira Daniela , Dias Maria Inês , Barros Lillian , Custódio Luísa , Oliveira Rui
Published: March 2023

Long-term exposure to dietary xenobiotics can induce oxidative stress in the gastrointestinal tract, possibly causing DNA damage and contributing to the initiation of carcinogenesis. Halophytes are exposed to constant abiotic stresses, which are believed to promote the accumulation of antioxidant metabolites like polyphenols. The aim of this study was to evaluate the antioxidant and antigenotoxic properties of the ethanol extract of the aerial part of the halophyte Polygonum maritimum L. (PME), which can represent a dietary source of bioactive compounds with potential to attenuate oxidative stress-related damage. The PME exhibited a high antioxidant potential, revealed by the in vitro capacity to scavenge the free radical DPPH (IC50 = 2.29 ± 0.10 μg/mL) and the improved viability of the yeast Saccharomyces cerevisiae under oxidative stress (p < 0.001, 10 min). An antigenotoxic effect of PME against H2O2-induced oxidative stress was found in S. cerevisiae (p < 0.05) with the dominant deletion assay. In vitro colorimetric assays and LC-DAD-ESI/MSn analysis showed that PME is a polyphenol-rich extract composed of catechin, (epi)catechin dimer and trimers, quercetin and myricetin glycosides. Hence, P. maritimum is a source of antioxidant and antigenotoxic metabolites for application in industries that develop products to provide health benefits.
Artificial intelligence-aided method to detect uterine fibroids in ultrasound images: a retrospective study
Authors: Huo Tongtong , Li Lixin , Chen Xiting , Wang Ziyi , Zhang Xiaojun , Liu Songxiang , Huang Jinfa , Zhang Jiayao , Yang Qian , Wu Wei , Xie Yi , Wang Honglin , Ye Zhewei , Deng Kaixian
Published: March 2023

We explored a new artificial intelligence-assisted method to assist junior ultrasonographers in improving the diagnostic performance of uterine fibroids and further compared it with senior ultrasonographers to confirm the effectiveness and feasibility of the artificial intelligence method. In this retrospective study, we collected a total of 3870 ultrasound images from 667 patients with a mean age of 42.45 years ± 6.23 [SD] for those who received a pathologically confirmed diagnosis of uterine fibroids and 570 women with a mean age of 39.24 years ± 5.32 [SD] without uterine lesions from Shunde Hospital of Southern Medical University between 2015 and 2020. The DCNN model was trained and developed on the training dataset (2706 images) and internal validation dataset (676 images). To evaluate the performance of the model on the external validation dataset (488 images), we assessed the diagnostic performance of the DCNN with ultrasonographers possessing different levels of seniority. The DCNN model aided the junior ultrasonographers (Averaged) in diagnosing uterine fibroids with higher accuracy (94.72% vs. 86.63%, P < 0.001), sensitivity (92.82% vs. 83.21%, P = 0.001), specificity (97.05% vs. 90.80%, P = 0.009), positive predictive value (97.45% vs. 91.68%, P = 0.007), and negative predictive value (91.73% vs. 81.61%, P = 0.001) than they achieved alone. Their ability was comparable to that of senior ultrasonographers (Averaged) in terms of accuracy (94.72% vs. 95.24%, P = 0.66), sensitivity (92.82% vs. 93.66%, P = 0.73), specificity (97.05% vs. 97.16%, P = 0.79), positive predictive value (97.45% vs. 97.57%, P = 0.77), and negative predictive value (91.73% vs. 92.63%, P = 0.75). The DCNN-assisted strategy can considerably improve the uterine fibroid diagnosis performance of junior ultrasonographers to make them more comparable to senior ultrasonographers.
Applying an ecosystem services framework on nature and mental health to recreational blue space visits across 18 countries
Authors: Garrett Joanne K. , White Mathew P. , Elliott Lewis R. , Grellier James , Bell Simon , Bratman Gregory N. , Economou Theo , Gascon Mireia , Lõhmus Mare , Nieuwenhuijsen Mark , Ojala Ann , Roiko Anne , van den Bosch Matilda , Ward Thompson Catharine , Fleming Lora E.
Published: March 2023

The effects of ‘nature’ on mental health and subjective well-being have yet to be consistently integrated into ecosystem service models and frameworks. To address this gap, we used data on subjective mental well-being from an 18-country survey to test a conceptual model integrating mental health with ecosystem services, initially proposed by Bratman et al. We analysed a range of individual and contextual factors in the context of 14,998 recreational visits to blue spaces, outdoor environments which prominently feature water. Consistent with the conceptual model, subjective mental well-being outcomes were dependent upon on a complex interplay of environmental type and quality, visit characteristics, and individual factors. These results have implications for public health and environmental management, as they may help identify the bluespace locations, environmental features, and key activities, that are most likely to impact well-being, but also potentially affect recreational demand on fragile aquatic ecosystems.
CRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization
Authors: Park Jinkyu , Cui Gang , Lee Hyundong , Jeong Han , Kwak Jay Jiyong , Lee Junwon , Byeon Suk Ho
Published: March 2023

The CRISPR/Cas9 system easily edits target genes in various organisms and is used to treat human diseases. In most therapeutic CRISPR studies, ubiquitously expressed promoters, such as CMV, CAG, and EF1α, are used; however, gene editing is sometimes necessary only in specific cell types relevant to the disease. Therefore, we aimed to develop a retinal pigment epithelium (RPE)-specific CRISPR/Cas9 system. We developed a CRISPR/Cas9 system that operates only in retinal pigment epithelium (RPE) by expressing Cas9 under the RPE-specific vitelliform macular dystrophy 2 promoter (pVMD2). This RPE-specific CRISPR/pVMD2-Cas9 system was tested in human retinal organoid and mouse model. We confirmed that this system works specifically in the RPE of human retinal organoids and mouse retina. In addition, the RPE-specific Vegfa ablation using the novel CRISPR-pVMD2-Cas9 system caused regression of choroidal neovascularization (CNV) without unwanted knock-out in the neural retina in laser-induced CNV mice, which is a widely used animal model of neovascular age-related macular degeneration. RPE-specific Vegfa knock-out (KO) and ubiquitous Vegfa KO were comparable in the efficient regression of CNV. The promoter substituted, cell type-specific CRISPR/Cas9 systems can be used in specific ‘target cell’ therapy, which edits genes while reducing unwanted off- ‘target cell’ effects.
Machine learning for detecting DNA attachment on SPR biosensor
Authors: Mondal Himadri Shekhar , Ahmed Khandaker Asif , Birbilis Nick , Hossain Md Zakir
Published: March 2023

Optoelectric biosensors measure the conformational changes of biomolecules and their molecular interactions, allowing researchers to use them in different biomedical diagnostics and analysis activities. Among different biosensors, surface plasmon resonance (SPR)-based biosensors utilize label-free and gold-based plasmonic principles with high precision and accuracy, allowing these gold-based biosensors as one of the preferred methods. The dataset generated from these biosensors are being used in different machine learning (ML) models for disease diagnosis and prognosis, but there is a scarcity of models to develop or assess the accuracy of SPR-based biosensors and ensure a reliable dataset for downstream model development. Current study proposed innovative ML-based DNA detection and classification models from the reflective light angles on different gold surfaces of biosensors and associated properties. We have conducted several statistical analyses and different visualization techniques to evaluate the SPR-based dataset and applied t-SNE feature extraction and min-max normalization to differentiate classifiers of low-variances. We experimented with several ML classifiers, namely support vector machine (SVM), decision tree (DT), multi-layer perceptron (MLP), k-nearest neighbors (KNN), logistic regression (LR) and random forest (RF) and evaluated our findings in terms of different evaluation metrics. Our analysis showed the best accuracy of 0.94 by RF, DT and KNN for DNA classification and 0.96 by RF and KNN for DNA detection tasks. Considering area under the receiver operating characteristic curve (AUC) (0.97), precision (0.96) and F1-score (0.97), we found RF performed best for both tasks. Our research shows the potentiality of ML models in the field of biosensor development, which can be expanded to develop novel disease diagnosis and prognosis tools in the future.
The impact of N-glycosylation on the properties of the antimicrobial peptide LL-III
Authors: Tortorella Attila , Leone Linda , Lombardi Angelina , Pizzo Elio , Bosso Andrea , Winter Roland , Petraccone Luigi , Del Vecchio Pompea , Oliva Rosario
Published: March 2023

The misuse of antibiotics has led to the emergence of drug-resistant pathogens. Antimicrobial peptides (AMPs) may represent valuable alternative to antibiotics; nevertheless, the easy degradation due to environmental stress and proteolytic enzyme action, limits their use. So far, different strategies have been developed to overcome this drawback. Among them, glycosylation of AMPs represents a promising approach. In this work, we synthesized and characterized the N-glycosilated form of the antimicrobial peptide LL-III (g-LL-III). The N-acetylglucosamine (NAG) was covalently linked to the Asn residue and the interaction of g-LL-III with bacterial model membranes, together with its resistance to proteases, were investigated. Glycosylation did not affect the peptide mechanism of action and its biological activity against both bacteria and eukaryotic cells. Interestingly, a higher resistance to the activity of proteolytic enzymes was achieved. The reported results pave the way for the successful application of AMPs in medicine and biotechnological fields.
Anatomical and functional outcomes of short-term DensironXTRA heavy silicone oil for rhegmatogenous retinal detachments: a comparative case series
Authors: Felfeli Tina , Murtaza Fahmeeda , Herman Joshua , Pereira Austin M. , Mandelcorn Mark S. , Mandelcorn Efrem D.
Published: March 2023

To assess the safety and efficacy of short-term DensironXTRA tamponade for repair of complicated rhegmatogenous retinal detachments (RRD). This is a retrospective consecutive case series of patients undergoing pars plana vitrectomy (PPV) with intravitreal DensironXTRA and a comparator group with gas (sulfur hexafluoride (SF6) or perfluoropropane (C3F8)) tamponades by a single surgeon between January 2017 and November 2020 at a tertiary care centre. A total of 121 eyes with DensironXTRA and 81 comparator eyes with a gas tamponade were included. The DensironXTRA group had a significantly higher number of cases with inferior breaks (82% vs. 48%; p < 0.0001) and a history of previous PPV for RRD (64% vs. 12%; p < 0.0001). DensironXTRA was removed after a median period of 70 (IQR: 48.5–105.5) days. There was similar anatomical success in both the comparator gas tamponade and DensironXTRA groups (98.8% vs. 97.5%, p = 0.6506). Although both groups experienced a significant improvement in visual acuity, this change was significantly higher in the comparator gas tamponade group versus DensironXTRA group (p = 0.0017). There was no significant change in IOP in the DensironXTRA group (mean difference − 0.7; 95% CI − 1.753 to 0.331, p = 0.1785). The rates of complications were low and not significantly different between the two groups. There was no evidence for central macular thinning with DensironXTRA compared to the contralateral eye without RRD as well as with DensironXTRA in situ versus after its removal. DensironXTRA is a promising short-term tamponade agent with good anatomical and functional outcomes and low rates of complications for the repair of complicated RRDs.
Gemcitabine–cisplatin versus MVAC chemotherapy for urothelial carcinoma: a nationwide cohort study
Authors: Lee Yong Seong , Ha Moon Soo , Tae Jong Hyun , Chang In Ho , Kim Tae-Hyoung , Myung Soon Chul , Nguyen Tuan Thanh , Kim Myoungsuk , Lee Kyung-Eun , Kim Yuwon , Woo Hyun-ki , Kyoung Dae-Sung , Kim Hasung , Choi Se Young
Published: March 2023

This study assessed the trends in methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine–cisplatin (GC) regimens in Korean patients with metastatic urothelial carcinoma (UC) and compared the side effects and overall survival (OS) rates of the two regimens using nationwide population-based data. The data of patients diagnosed with UC between 2004 and 2016 were collected using the National Health Insurance Service database. The overall treatment trends were assessed according to the chemotherapy regimens. The MVAC and GC groups were matched by propensity scores. Cox proportional hazard analysis and Kaplan–Meier analysis were performed to assess survival. Of 3108 patients with UC, 2,880 patients were treated with GC and 228 (7.3%) were treated with MVAC. The transfusion rate and volume were similar in both the groups, but the granulocyte colony-stimulating factor (G-CSF) usage rate and number were higher in the MVAC group than in the GC group. Both groups had similar OS. Multivariate analysis revealed that the chemotherapy regimen was not a significant factor for OS. Subgroup analysis revealed that a period of ≥ 3 months from diagnosis to systemic therapy enhanced the prognostic effects of the GC regimen. The GC regimen was widely used as the first-line chemotherapy in more than 90% of our study population with metastatic UC. The MVAC regimen showed similar OS to the GC regimen but needed greater use of G-CSF. The GC regimen could be a suitable treatment option for metastatic UC after ≥ 3 months from diagnosis.
The research of a novel WOG-YOLO algorithm for autonomous driving object detection
Authors: Xu Lingzhi , Yan Wei , Ji Jiashu
Published: March 2023

Object detection has been one of the critical technologies in autonomous driving. To improve the detection precision, a novel optimization algorithm is presented to enhance the performance of the YOLOv5 model. First, by improving the hunting behavior of the grey wolf algorithm(GWO) and incorporating it into the whale optimization algorithm(WOA), a modified whale optimization algorithm(MWOA) is proposed. The MWOA leverages the population’s concentration ratio to calculate $$p_h$$

p
h

for selecting the hunting branch of GWO or WOA. Tested by six benchmark functions, MWOA is proven to possess better global search ability and stability. Second, the C3 module in YOLOv5 is substituted by G-C3, and an extra detection head is added, thus a highly optimizable detection G-YOLO network is constructed. Based on the self-built dataset, 12 initial hyperparameters in the G-YOLO model are optimized by MWOA using a score fitness function of compound indicators, thus the final hyperparameters are optimized and the whale optimization G-YOLO (WOG-YOLO) model is obtained. In comparison with the YOLOv5s model, the overall mAP increases by 1.7$$\%$$
%
, the mAP of pedestrians increases by 2.6$$\%$$
%
and the mAP of cyclists increases by 2.3$$\%$$
%
.
Resculpting carbon dots via electrochemical etching
Authors: Yang Qingsong , Gavalas Spyridon , Ejsmont Aleksander , Krysmann Marta J. , Guo Jiangtao , Li Li , Guo Xuhong , Kelarakis Antonios
Published: March 2023

Substantial efforts are directed into exploring the structure-properties relationships of photoluminescent Carbon dots (C-dots). This study unravels a resculpting mechanism in C-dots that is triggered by electrochemical etching and proceeds via extensive surface oxidation and carbon–carbon breakage. The process results in the gradual shrinkage of the nanoparticles and can enhance the quantum yield by more than half order of magnitude compared to the untreated analogues.