bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainty Analysis in Multi‐Sector Systems: Considerations for Risk Analysis, Projection, and Planning for Complex Systems
Authors: Srikrishnan Vivek , Lafferty David C. , Wong Tony E. , Lamontagne Jonathan R. , Quinn Julianne D. , Sharma Sanjib , Molla Nusrat J. , Herman Jonathan D. , Sriver Ryan L. , Morris Jennifer F. , Lee Ben Seiyon
Published: August 2022

Simulation models of multi‐sector systems are increasingly used to understand societal resilience to climate and economic shocks and change. However, multi‐sector systems are also subject to numerous uncertainties that prevent the direct application of simulation models for prediction and planning, particularly when extrapolating past behavior to a nonstationary future. Recent studies have developed a combination of methods to characterize, attribute, and quantify these uncertainties for both single‐ and multi‐sector systems. Here, we review challenges and complications to the idealized goal of fully quantifying all uncertainties in a multi‐sector model and their interactions with policy design as they emerge at different stages of analysis: (a) inference and model calibration; (b) projecting future outcomes; and (c) scenario discovery and identification of risk regimes. We also identify potential methods and research opportunities to help navigate the tradeoffs inherent in uncertainty analyses for complex systems. During this discussion, we provide a classification of uncertainty types and discuss model coupling frameworks to support interdisciplinary collaboration on multi‐sector dynamics (MSD) research. Finally, we conclude with recommendations for best practices to ensure that MSD research can be properly contextualized with respect to the underlying uncertainties.
Future Characteristics of Extreme Precipitation Indicate the Dominance of Frequency Over Intensity: A Multi‐Model Assessment From CMIP6 Across India
Authors: Sarkar Subharthi , Maity Rajib
Published: August 2022

This study presents a comprehensive analysis on the past and future changes in precipitation extremes and quantifies the relative contributions from its frequency and intensity across India, considering five extremeness levels, denoted by 95th, 99th, 99.9th, 99.95th, and 99.97th percentile. Gridded station‐based observations from the historical period (1951–2020) and simulations from 14 General Circulation Models for the future (2021–2100), participating in the Coupled Model Intercomparison Project phase 6 (CMIP6) are considered. Apart from an overall increasing pattern of precipitation extremes, it is noticed that the contribution of frequency dominates over intensity. Specifically, the frequency of 99th percentile daily rainfall is projected to increase approximately by two‐ (SSP245) to three‐ (SSP585) times in future. We also proposed a new zoning of entire Indian mainland, identified as six Homogeneous Precipitation Zones (HPZs). HPZ‐wise analysis reveals that the increase in frequency dominates over intensity for all the HPZs with a varying extent. For instance, increase in frequency is more for the climatologically high‐precipitation zones (HPZ‐3: Western Ghats, and HPZ‐6: North‐east India), whereas increase in intensity is more for the low‐precipitation zones (HPZ‐1: North‐west India, and HPZ‐4: Peninsular India). The degree of increase gets even more pronounced under the worst scenario SSP585, indicating a potential impact of anthropogenic activities on changing precipitation extremes. Findings of this study should be accounted in the climate change adaptation and mitigation strategies for future.
Assessing the Internal Uppermost Crustal Structure of the Central Pyrenees by Gravity‐Constrained Cross Sections
Authors: Soto Ruth , Clariana Pilar , Ayala Conxi , Rey‐Moral Carmen , Casas‐Sainz Antonio M. , Román‐Berdiel Teresa , Margalef Aina , Rubio Félix , Oliva‐Urcia Belén , Pueyo Emilio L. , Martín‐León Juliana , Beamud Elisabet
Published: August 2022

The Pyrenees constitutes an exceptional example of an Alpine orogenic belt characterized by basement thrust sheets involving Paleozoic rocks and Mesozoic and Cenozoic cover units detached on the Triassic evaporites, the main décollement level. This work is located in the Central Pyrenees, where gravity data help to better constrain the internal architecture of the upper crust of the southern half of the Axial Zone and the northern part of the South Pyrenean Zone, a key area to understand the orogenic evolution of the chain. Previous and new gravity, petrophysical and geological data have been used to obtain the Bouguer and residual anomaly maps of the study area and six serial gravity‐constrained cross sections perpendicular to the main structural trend. The residual anomaly map shows a good correlation between basement units involved in thrust sheets of the study area and gravity highs whereas negative anomalies are interpreted to correspond with Mesozoic/Cenozoic basins, Triassic evaporites, Late Variscan igneous bodies, and Ordovician gneisses. The six gravity‐constrained cross sections highlight strong along‐strike variations on the gravity signal due to lateral differences of the superficial and subsurface occurrence of Triassic evaporites, different geometry at depth of the Late Variscan igneous bodies outcropping in the study area, and geometric lateral variations of the basement thrust sheets and their relationship with the Mesozoic‐Cenozoic units.
Distinguishing Direct Human‐Driven Effects on the Global Terrestrial Water Cycle
Authors: Kåresdotter Elisie , Destouni Georgia , Ghajarnia Navid , Lammers Richard B. , Kalantari Zahra
Published: August 2022

Population growth is increasing the pressure on water resource availability. For useful assessment and planning for societal water availability impacts, it is imperative to disentangle the direct influences of human activities in the landscape from external climate‐driven influences on water flows and their variation and change. In this study we used the water balance model, a gridded global hydrological model, to quantify and distinguish human‐driven change components, modified by interventions such as dams, reservoirs, and water withdrawals for irrigation, industry, and households, from climate‐driven change components on four key water balance variables in the terrestrial hydrological system (evapotranspiration, runoff, soil moisture, storage change). We also analyzed emergent effect patterns in and across different parts of the world, facilitating exploration of spatial variability and regional patterns on multiple spatial scales, from pixel to global, including previously uninvestigated parts of the world. Our results show that human activities drive changes in all hydrological variables, with different magnitudes and directions depending on geographical location. The differences between model scenarios with and without human activities were largest in regions with the highest population densities. In such regions, which also have relatively large numbers of dams for irrigation, water largely tends to be removed from storage and go to feed increased runoff and evapotranspiration fluxes. Our analysis considers a more complete set of hydrological variables than previous studies and can guide further research and management planning for future hydrological and water availability trends, including in relatively data‐poor parts of the world.
EdgePhase: A Deep Learning Model for Multi‐Station Seismic Phase Picking
Authors: Feng Tian , Mohanna Saeed , Meng Lingsen
Published: August 2022

In this study, we build a multi‐station phase‐picking model named EdgePhase by integrating an Edge Convolutional module with a state‐of‐the‐art single‐station phase‐picking model, EQTransformer. The Edge Convolutional module, a variant of Graph Neural Network, exchanges information relevant to seismic phases between neighboring stations. In EdgePhase, seismograms are first encoded into the latent representations, then converted into enhanced representations by the Edge Convolutional module, and finally decoded into the P‐ and S‐phase probabilities. Compared to the standard EQTransformer, EdgePhase increases the precision (fraction of phase identifications that are real) and recall (fraction of phase arrivals that are identified) rate by 5% on our training and test data sets of Southern California earthquakes. To evaluate its performance in regions of different tectonic settings, we applied EdgePhase to detect the early aftershocks following the 2020 M7.0 Samos, Greece earthquake. Compared to a local earthquake catalog, EdgePhase produced 190% additional detections with an event distribution more conformative to a planar fault interface, suggesting higher fidelity in event locations. This case study indicates that EdgePhase provides a strong regional generalization capability in real‐world applications.
Stirring and Mixing in the Wake of Velasco Reef, Palau
Authors: Johnston T. M. Shaun , Rudnick Daniel L.
Published: August 2022

Over 2 years, underwater gliders measured currents, temperature, and salinity along lines 40 km up‐ and downstream of the abrupt topography of Palau to examine topographic effects on the incident flow. The mean flow is westward and is associated with the North Equatorial Current. Salinity on isopycnals is a passive tracer. During westward flow, this tracer variance is elevated downstream in the strongest flow north of the topography at scales of 36 km (evaluated from 12 to 60 km) consistent with a wake eddy at the scale of the topography. During eastward flow, variance is elevated downstream at all measured scales. This result suggests eddies are trapped at the topography because westward eddy propagation is opposed by the incident eastward flow. This time‐mean tracer and current structure up‐ and downstream are used to estimate terms in the advection‐diffusion equation. The mean isopycnal diffusivity is about 17 times greater than background values at 36‐km scales (and 40 times greater within 20 km of the topography), while the mean diapycnal diffusivity is 100 times greater than background values for this latitude. The contrast between up‐and downstream salinity on isopycnals can reach 0.2 psu over 5–10 km, which is seen in the glider measurements and one ship‐based survey. This contrast arises due to eddies detaching from the North Equatorial Countercurrent or its recirculations. These episodes are associated with westward‐propagating, intraseasonal Rossby waves.
A state-of-the-science review and guide for measuring environmental exposure biomarkers in dried blood spots
Authors: Jacobson Tyler A. , Kler Jasdeep S. , Bae Yeunook , Chen Jiexi , Ladror Daniel T. , Iyer Ramsunder , Nunes Denise A. , Montgomery Nathan D. , Pleil Joachim D. , Funk William E.
Published: August 2022

Background

Dried blood spot (DBS) sampling is a simple, cost-effective, and minimally invasive alternative to venipuncture for measuring exposure biomarkers in public health and epidemiological research. DBS sampling provides advantages in field-based studies conducted in low-resource settings and in studies involving infants and children. In addition, DBS samples are routinely collected from newborns after birth (i.e., newborn dried blood spots, NDBS), with many states in the United States permitting access to archived NDBS samples for research purposes.

Objectives

We review the state of the science for analyzing exposure biomarkers in DBS samples, both archived and newly collected, and provide guidance on sample collection, storage, and blood volume requirements associated with individual DBS assays. We discuss recent progress regarding analytical methods, analytical sensitivity, and specificity, sample volume requirements, contamination considerations, estimating extracted blood volumes, assessing stability and analyte recovery, and hematocrit effects.

Methods

A systematic search of PubMed (MEDLINE), Embase (Elsevier), and CINAHL (EBSCO) was conducted in March 2022. DBS method development and application studies were divided into three main chemical classes: environmental tobacco smoke, trace elements (including lead, mercury, cadmium, and arsenic), and industrial chemicals (including endocrine-disrupting chemicals and persistent organic pollutants). DBS method development and validation studies were scored on key quality-control and performance parameters by two members of the review team.

Results

Our search identified 47 published reports related to measuring environmental exposure biomarkers in human DBS samples. A total of 28 reports (37 total studies) were on methods development and validation and 19 reports were primarily the application of previously developed DBS assays. High-performing DBS methods have been developed, validated, and applied for detecting environmental exposures to tobacco smoke, trace elements, and several important endocrine-disrupting chemicals and persistent organic pollutants. Additional work is needed for measuring cadmium, arsenic, inorganic mercury, and bisphenol A in DBS and NDBS samples.

Significance

We present an inventory and critical review of available assays for measuring environmental exposure biomarkers in DBS and NDBS samples to help facilitate this sampling medium as an emerging tool for public health (e.g., screening programs, temporal biomonitoring) and environmental epidemiology (e.g., field-based studies).
Regulated cell death (RCD) in cancer: key pathways and targeted therapies
Authors: Peng Fu , Liao Minru , Qin Rui , Zhu Shiou , Peng Cheng , Fu Leilei , Chen Yi , Han Bo
Published: August 2022

Regulated cell death (RCD), also well-known as programmed cell death (PCD), refers to the form of cell death that can be regulated by a variety of biomacromolecules, which is distinctive from accidental cell death (ACD). Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis, which may ultimately lead to the establishment of different potential therapeutic strategies. Hitherto, targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue, which has rapidly progressed in many types of human cancers. Thus, in this review, we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways, but the crucial pathways of other RCD subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis and lysosome-dependent cell death (LCD) in cancer. Moreover, we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment, such as single-target, dual or multiple-target small-molecule compounds, drug combinations, and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.
The overlooked role of a biotin precursor for marine bacteria - desthiobiotin as an escape route for biotin auxotrophy
Authors: Wienhausen Gerrit , Bruns Stefan , Sultana Sabiha , Dlugosch Leon , Groon Luna-Agrippina , Wilkes Heinz , Simon Meinhard
Published: August 2022

Biotin (vitamin B7) is involved in a wide range of essential biochemical reactions and a crucial micronutrient that is vital for many pro- and eukaryotic organisms. The few biotin measurements in the world’s oceans show that availability is subject to strong fluctuations. Numerous marine microorganisms exhibit biotin auxotrophy and therefore rely on supply by other organisms. Desthiobiotin is the primary precursor of biotin and has recently been detected at concentrations similar to biotin in seawater. The last enzymatic reaction in the biotin biosynthetic pathway converts desthiobiotin to biotin via the biotin synthase (BioB). The role of desthiobiotin as a precursor of biotin synthesis in microbial systems, however, is largely unknown. Here we demonstrate experimentally that bacteria can overcome biotin auxotrophy if they retain the bioB gene and desthiobiotin is available. A genomic search of 1068 bacteria predicts that the biotin biosynthetic potential varies greatly among different phylogenetic groups and that 20% encode solely bioB and thus can potentially overcome biotin auxotrophy. Many Actino- and Alphaproteobacteria cannot synthesize biotin de novo, but some possess solely bioB, whereas the vast majority of Gammaproteobacteria and Flavobacteriia exhibit the last four crucial biotin synthesis genes. We detected high intra- and extracellular concentrations of the precursor relative to biotin in the prototrophic bacterium, Vibrio campbellii, with extracellular desthiobiotin reaching up to 1.09 ± 0.15*106 molecules per cell during exponential growth. Our results provide evidence for the ecological role of desthiobiotin as an escape route to overcome biotin auxotrophy for bacteria in the ocean and presumably in other ecosystems.
Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data
Authors: Tafazoli Alireza , van der Lee Maaike , Swen Jesse J. , Zeller Anna , Wawrusiewicz-Kurylonek Natalia , Mei Hailiang , Vorderman Ruben H. P. , Konopko Krzysztof , Zankiewicz Andrzej , Miltyk Wojciech
Published: August 2022

This pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified. Four publicly available PGx bioinformatics algorithms to assign PGx haplotypes were applied to nine selected very important pharmacogenes (VIP) and revealed a 45–70% concordance rate. To ensure availability of the results at point-of-care, actionable variants were stored in a web-hosted database and PGx-cards were developed for quick access and handed to the study subjects. While a comprehensive clinical PGx profile could be successfully extracted from WES data, available tools to interpret these data demonstrated inconsistencies that complicate clinical application.
ACSL4-dependent ferroptosis does not represent a tumor-suppressive mechanism but ACSL4 rather promotes liver cancer progression
Authors: Grube Julia , Woitok Marius Maximilian , Mohs Antje , Erschfeld Stephanie , Lynen Celina , Trautwein Christian , Otto Tobias
Published: August 2022

Ferroptosis is a novel type of programmed cell death that differs from apoptosis in that it involves iron-dependent peroxidation of membrane phospholipids. Its role in a variety of human disorders, including cancer has been hypothesized in recent years. While it may function as an endogenous tumor suppressor in a variety of cancers, its role during initiation and progression of liver cancer, particularly hepatocellular carcinoma (HCC), is yet unknown. Because HCC is most commonly found in chronically injured livers, we utilized two well-established mouse models of chronic injury-dependent HCC formation: Treatment with streptozotocin and high-fat diet as metabolic injury model, as well as treatment with diethylnitrosamine and carbon tetrachloride as toxic injury model. We used mice with hepatocyte-specific deletion of Acsl4, a key mediator of ferroptosis, to explore the significance of ferroptotic cell death in hepatocytes, the cell type of origin for HCC. Surprisingly, preventing ferroptotic cell death in hepatocytes by deleting Acsl4 does not increase the formation of HCC. Furthermore, Acsl4-deficient livers display less fibrosis and proliferation, especially in the HCC model of toxic damage. Intriguingly, in this model, the absence of ACSL4-dependent processes such as ferroptosis significantly slow down the growth of HCC. These findings suggest that during HCC formation in a chronically injured liver, ferroptotic cell death is not an endogenous tumor-suppressive mechanism. Instead, we find that ACSL4-dependent processes have an unanticipated cancer-promoting effect during HCC formation, which is most likely due to aggravated liver damage as demonstrated by increased hepatic fibrosis. Previous studies suggested that ferroptosis might have beneficial effects for patients during HCC therapy. As a result, during HCC progression and therapy, ferroptosis may have both cancer-promoting and cancer-inhibitory effects, respectively.
lncRNA CYTOR promotes aberrant glycolysis and mitochondrial respiration via HNRNPC-mediated ZEB1 stabilization in oral squamous cell carcinoma
Authors: Zhu Weiwen , Wang Jie , Liu Xiang , Xu Yanbin , Zhai Rundong , Zhang Jiayi , Wang Mengqi , Wang Mengyao , Liu Laikui
Published: August 2022

Oral squamous cell carcinoma (OSCC), the most common malignancy of the oral and maxillofacial region, severely affects human health. However, current treatments for OSCC commonly show only a ~60% 5-year survival rate of patients with distant metastases, indicating an urgent need for targeted treatments for patients with advanced metastases. Here, we report a survival-related long non-coding RNA, CYTOR, which is highly expressed in the lesions of oral cancer patients. We found that CYTOR can promote both migration and invasion in oral cancer cells as well as the epithelial–mesenchymal transition (EMT). RNA-sequencing of CYTOR-knockdown oral cancer cells revealed that CYTOR can regulate mitochondrial respiration and RNA splicing. Mechanistically, we found that nuclear-localized CYTOR interacts with HNRNPC, resulting in stabilization of ZEB1 mRNAs by inhibiting the nondegradative ubiquitination of HNRNPC. By synthesizing CYTOR-targeting small interfering RNAs (siRNAs) encapsulated in Nanoscale Metal Organic Frameworks (NMOFs), we demonstrate the targeted suppression of CYTOR to inhibit invasion and metastasis of oral cancer cells in a nude mouse model. Cumulatively, this study reveals the potential role of the CYTOR-HNRNPC-ZEB1 axis in regulating mitochondrial metabolism and glycolysis of oral cancer cells, and illustrates the effective use of lncRNA targeting in anti-metastatic cancer therapies.
KCNK3 inhibits proliferation and glucose metabolism of lung adenocarcinoma via activation of AMPK-TXNIP pathway
Authors: Lin Guofu , Lin Lanlan , Lin Hai , Chen Wenhan , Chen Luyang , Chen Xiaohui , Chen Shaohua , Lin Qinhui , Xu Yuan , Zeng Yiming
Published: August 2022

Non-small cell lung cancer (NSCLC) is a primary histological subtype of lung cancer with increased morbidity and mortality. K+ channels have been revealed to be involved in carcinogenesis in various malignant tumors. However, TWIK-related acid-sensitive potassium channel 1 (TASK-1, also called KCNK3), a genetic member of K2P channels, remains an enigma in lung adenocarcinoma (LUAD). Herein, we investigated the pathological process of KCNK3 in proliferation and glucose metabolism of LUAD. The expressions of KCNK3 in LUAD tissues and corresponding adjacent tissues were identified by RNA sequencing, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry. Gain and loss-of-function assays were performed to estimate the role of KCNK3 in proliferation and glucose metabolism of LUAD. Additionally, energy metabolites of LUAD cells were identified by targeted metabolomics analysis. The expressions of metabolic molecules and active biomarkers associated with AMPK-TXNIP signaling pathway were detected via western blot and immunofluorescence. KCNK3 was significantly downregulated in LUAD tissues and correlated with patients’ poor prognosis. Overexpression of KCNK3 largely regulated the process of oncogenesis and glycometabolism in LUAD in vitro and in vivo. Mechanistic studies found that KCNK3-mediated differential metabolites were mainly enriched in AMPK signaling pathway. Furthermore, rescue experiments demonstrated that KCNK3 suppressed proliferation and glucose metabolism via activation of the AMPK-TXNIP pathway in LUAD cells. In summary, our research highlighted an emerging role of KCNK3 in the proliferative activity and glycometabolism of LUAD, suggesting that KCNK3 may be an optimal predictor for prognosis and a potential therapeutic target of LUAD.
LncRNA in tumorigenesis of non-small-cell lung cancer: From bench to bedside
Authors: Hu Qin , Ma Huiyun , Chen Hongyu , Zhang Zhouwei , Xue Qun
Published: August 2022

Lung cancer has been one of the leading causes of cancer-related death worldwide, and non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancer morbidity, yet the pathogenesis of NSCLC has not been fully elucidated. Recently, long-chain non-coding RNA (lncRNA) has attracted widespread attention. LncRNA is a type of non-coding RNA whose transcript length exceeds 200 nucleotides. After constant research, academics updated their understanding of lncRNA, especially its role in the biological processes of cancer cells, including epigenetic regulation, cell proliferation, and cell differentiation. Notably, examination of lncRNAs could serve as potential hallmarks for clinicopathological features, long-term prognosis, and drug sensitivity. Therefore, it is necessary to explore the functions of lncRNA in NSCLC and innovate potential strategies against NSCLC based on lncRNA-related research. Herein, we reviewed the functions of lncRNA in the occurrence, diagnosis, treatment, and prognosis of NSCLC, which not only help promote a comprehensive view of lncRNA in NSCLC, but also shed light on the potential of lncRNA-based diagnosis and treatment of NSCLC.
Zero dispersion Kerr solitons in optical microresonators
Authors: Anderson Miles H. , Weng Wenle , Lihachev Grigory , Tikan Alexey , Liu Junqiu , Kippenberg Tobias J.
Published: August 2022

Solitons are shape preserving waveforms that are ubiquitous across nonlinear dynamical systems from BEC to hydrodynamics, and fall into two separate classes: bright solitons existing in anomalous group velocity dispersion, and switching waves forming ‘dark solitons’ in normal dispersion. Bright solitons in particular have been relevant to chip-scale microresonator frequency combs, used in applications across communications, metrology, and spectroscopy. Both have been studied, yet the existence of a structure between this dichotomy has only been theoretically predicted. We report the observation of dissipative structures embodying a hybrid between switching waves and dissipative solitons, existing in the regime of vanishing group velocity dispersion where third-order dispersion is dominant, hence termed as ‘zero-dispersion solitons’. They are observed to arise from the interlocking of two modulated switching waves, forming a stable solitary structure consisting of a quantized number of peaks. The switching waves form directly via synchronous pulse-driving of a Si3N4microresonator. The resulting comb spectrum spans 136 THz or 97% of an octave, further enhanced by higher-order dispersive wave formation. This dissipative structure expands the domain of Kerr cavity physics to the regime near to zero-dispersion and could present a superior alternative to conventional solitons for broadband comb generation.
Individuals with ventromedial frontal damage display unstable but transitive preferences during decision making
Authors: Yu Linda Q. , Dana Jason , Kable Joseph W.
Published: August 2022

The ventromedial frontal lobe (VMF) is important for decision-making, but the precise causal role of the VMF in the decision process has not been fully established. Previous studies have suggested that individuals with VMF damage violate transitivity, a hallmark axiom of rational decisions. However, these prior studies cannot properly distinguish whether individuals with VMF damage are truly prone to choosing irrationally from whether their preferences are simply more variable. We had individuals with focal VMF damage, individuals with other frontal damage, and healthy controls make repeated choices across three categories—artworks, chocolate bar brands, and gambles. Using proper tests of transitivity, we find that, in our study, individuals with VMF damage make rational decisions consistent with transitive preferences, even though they exhibit greater variability in their preferences. That is, the VMF is necessary for having strong and reliable preferences, but not for being a rational decision maker. VMF damage affects the variability with which value is assessed, but not the consistency with which value is sought.
Vaccine effectiveness of CoronaVac against COVID-19 among children in Brazil during the Omicron period
Authors: Florentino Pilar T. V. , Alves Flávia J. O. , Cerqueira-Silva Thiago , Oliveira Vinicius de Araújo , Júnior Juracy B. S. , Jantsch Adelson G. , Penna Gerson O. , Boaventura Viviane , Werneck Guilherme L. , Rodrigues Laura C. , Pearce Neil , Barral-Netto Manoel , Barreto Mauricio L. , Paixão Enny S.
Published: August 2022

Although severe COVID-19 in children is rare, they may develop multisystem inflammatory syndrome, long-COVID and downstream effects of COVID-19, including social isolation and disruption of education. Data on the effectiveness of the CoronaVac vaccine is scarce during the Omicron period. In Brazil, children between 6 to 11 years are eligible to receive the CoronaVac vaccine. We conducted a test-negative design to estimate vaccine effectiveness using 197,958 tests from January 21, 2022, to April 15, 2022, during the Omicron dominant period in Brazil among children aged 6 to 11 years. The estimated vaccine effectiveness for symptomatic infection was 39.8% (95% CI 33.7–45.4) at ≥14 days post-second dose. For hospital admission vaccine effectiveness was 59.2% (95% CI 11.3–84.5) at ≥14 days. Two doses of CoronaVac in children during the Omicron period showed low levels of protection against symptomatic infection, and modest levels against severe illness.
Empirical evidence on the efficiency of backward contact tracing in COVID-19
Authors: Raymenants Joren , Geenen Caspar , Thibaut Jonathan , Nelissen Klaas , Gorissen Sarah , Andre Emmanuel
Published: August 2022

Standard contact tracing practice for COVID-19 is to identify persons exposed to an infected person during the contagious period, assumed to start two days before symptom onset or diagnosis. In the first large cohort study on backward contact tracing for COVID-19, we extended the contact tracing window by 5 days, aiming to identify the source of the infection and persons infected by the same source. The risk of infection amongst these additional contacts was similar to contacts exposed during the standard tracing window and significantly higher than symptomatic individuals in a control group, leading to 42% more cases identified as direct contacts of an index case. Compared to standard practice, backward traced contacts required fewer tests and shorter quarantine. However, they were identified later in their infectious cycle if infected. Our results support implementing backward contact tracing when rigorous suppression of viral transmission is warranted.
An artificial neuromorphic somatosensory system with spatio-temporal tactile perception and feedback functions
Authors: Sun Fuqin , Lu Qifeng , Hao Mingming , Wu Yue , Li Yue , Liu Lin , Li Lianhui , Wang Yingyi , Zhang Ting
Published: August 2022

The advancement in flexible electronics and neuromorphic electronics has opened up opportunities to construct artificial perception systems to emulate biological functions which are of great importance for intelligent robotics and human-machine interactions. However, artificial systems that can mimic the somatosensory feedback functions have not been demonstrated yet despite the great achievement in this area. In this work, inspired by human somatosensory feedback pathways, an artificial somatosensory system with both perception and feedback functions was designed and constructed by integrating the flexible tactile sensors, synaptic transistor, artificial muscle, and the coupling circuit. Also, benefiting from the synaptic characteristics of the designed artificial synapse, the system shows spatio-temporal information-processing ability, which can further enhance the efficiency of the system. This research outcome has a potential contribution to the development of sensor technology from signal sensing to perception and cognition, which can provide a special paradigm for the next generation of bionic tactile perception systems towards e-skin, neurorobotics, and advanced bio-robots.
Multi-disciplinary community respiratory team management of patients with chronic respiratory illness during the COVID-19 pandemic
Authors: Turner Emily , Johnson Emma , Levin Kate , Gingles Stewart , Mackay Elaine , Roux Claire , Milligan Marianne , Mackie Marion , Farrell Kirsten , Murray Kirsty , Adams Suzanne , Brand Joan , Anderson David , Bayes Hannah
Published: August 2022

The Greater Glasgow & Clyde NHS Trust Community Respiratory Response Team was established to manage patients with chronic respiratory disease at home during the COVID-19 pandemic. The team aimed to avert hospital admission while maximally utilising remote consultations. This observational study analysed outcomes of the triage pathway used, use of remote consultations, hospital admissions and mortality among patients managed by the team. Patients’ electronic health records were retrospectively reviewed. Rates of emergency department attendance, hospital admission and death within 28 days of referral were compared across triage pathways. Segmented linear regression was carried out for emergency admissions in Greater Glasgow and Clyde pre- and post- Community Respiratory Response Team implementation, using emergency admissions for chronic obstructive pulmonary disease in the rest of Scotland as control and adjusting for all-cause emergency admissions. The triage category correlated with hospital admission and death. The red pathway had the highest proportion attending the emergency department (21%), significantly higher than the amber and green pathways (p = 0.03 and p = 0.004, respectively). The highest number of deaths were in the blue “end-of-life” pathway (p < 0.001). 87% of interactions were undertaken remotely. Triage severity appropriately led to targeted home visits. No nosocomial COVID-19 infections occurred among patients or staff. The Community Respiratory Response Team was associated with a significant decrease in emergency admissions (RR = 0.96 for each additional month under the Poisson model) compared to the counterfactual if the service had not been in place, suggesting a benefit in reducing secondary care pressures. The Community Respiratory Response Team effectively managed patients with chronic respiratory disease in the community, with an associated reduction in secondary care pressures during the COVID-19 pandemic.
Increasingly frequent extreme weather events urge the development of point-of-use water treatment systems
Authors: Wang Dawei , Chen Yuanyuan , Jarin Mourin , Xie Xing
Published: August 2022

The frequency of extreme weather events, including floods, storms, droughts, extreme temperatures, and wildfires, has intensified globally over recent decades due to climate change, affecting human society profoundly. Among all the impacts of these extreme weather events, the consequences to our reliable water supply have gained increasing attention as they exacerbate the inequities in health and education, especially in marginalized populations. In this perspective, we emphasize that extreme weather events are able to undermine a stable supply of drinking water through a number of approaches, and conventional centralized water treatment is insufficient at addressing these challenges. We urge that greater recognition, increased public awareness, and more efforts on technological innovation on decentralized, especially point-of-use (POU), water treatment should be prioritized to better help tackle the challenges faced by increasingly frequent extreme weather events.
A low-profile wideband compressed single-arm spiral antenna array for mid-band 5G beam steering applications
Authors: Falkner Benjamin J. , Zhou Hengyi , Zhang Wei , Metaxas Georgios , Mehta Amit , Ziegler Volker , Multerer Thomas , Mirshekar-Syahkal Dariush , Nakano Hisamatsu
Published: August 2022

A low profile wideband spiral antenna array is presented for global mid-band 5G beam steering applications. In the global rollout of mid-band 5G, different frequencies have been licensed within each region (e.g. 3.4–3.8 GHz in the EU and 3.7–5 GHz in the USA). Therefore, antenna arrays must be able to cover a bandwidth of 3.3 GHz to 5 GHz to provide true global coverage. Initially, this work presents the design of a wideband compressed spiral antenna that provides an axial beam throughout its operational bandwidth of 3.3 GHz to 5 GHz, enabling beam steering functionality. Then, this antenna has been placed in a 4 × 4 array with a triangular lattice. The proposed spiral antenna array can provide a scanning range of − 40° ≤ θ ≤  + 40° in all azimuth directions with an average back lobe level of less than − 9.5 dB. This development will allow for low-cost integration of 5G systems for global use, such as passenger aircraft, UAVs, drones, and marine and ground vehicles.
A high-throughput microfluidic device based on controlled incremental filtration to enable centrifugation-free, low extracorporeal volume leukapheresis
Authors: Lezzar Dalia L. , Lam Fong W. , Huerta Ravin , Mukhamedshin Anton , Lu Madeleine , Shevkoplyas Sergey S.
Published: August 2022

Leukapheresis, the extracorporeal separation of white blood cells (WBCs) from red blood cells (RBCs) and platelets (PLTs), is a life-saving procedure used for treating patients with cancer and other conditions, and as the initial step in the manufacturing of cellular and gene-based therapies. Well-tolerated by adults, leukapheresis poses a significant risk to neonates and low-weight infants because the extracorporeal volume (ECV) of standard centrifugation-based machines represents a particularly large fraction of these patients’ total blood volume. Here we describe a novel high-throughput microfluidic device (with a void volume of 0.4 mL) based on controlled incremental filtration (CIF) technology that could replace centrifugation for performing leukapheresis. The CIF device was tested extensively using whole blood from healthy volunteers at multiple hematocrits (5–30%) and flow rates (10–30 mL/min). In the flow-through regime, the CIF device separated WBCs with > 85% efficiency and 10–15% loss of RBCs and PLTs while processing whole blood diluted with saline to 10% hematocrit at a flow rate of 10 mL/min. In the recirculation regime, the CIF device demonstrated a similar level of separation performance, virtually depleting WBCs in the recirculating blood (~ 98% reduction) by the end of a 3.5-hour﻿ simulated leukapheresis procedure. Importantly, the device operated without clogging or decline in separation performance, with minimal activation of WBCs and PLTs and no measurable damage to RBCs. Compared to the typical parameters of centrifugation-based leukapheresis, the CIF device had a void volume at least 100-fold smaller, removed WBCs about twice as fast, and lost ~ 2–3-fold fewer PLTs, while operating at a flow rate compatible with the current practice. The hematocrit and flow rate at which the CIF device operated were significantly higher than previously published for other microfluidic cell separation methods. Finally, this study is the first to demonstrate a highly efficient separation of cells from recirculating blood using a microfluidic device. Overall, these findings suggest the feasibility of using high-throughput microfluidic cell separation technology to ultimately enable centrifugation-free, low-ECV leukapheresis. Such a capability would be particularly useful in young children, a vulnerable group of patients who are currently underserved.
Fly casting with ligand sliding and orientational selection supporting complex formation of a GPCR and a middle sized flexible molecule
Authors: Higo Junichi , Kasahara Kota , Bekker Gert-Jan , Ma Benson , Sakuraba Shun , Iida Shinji , Kamiya Narutoshi , Fukuda Ikuo , Kono Hidetoshi , Fukunishi Yoshifumi , Nakamura Haruki
Published: August 2022

A GA-guided multidimensional virtual-system coupled molecular dynamics (GA-mD-VcMD) simulation was conducted to elucidate binding mechanisms of a middle-sized flexible molecule, bosentan, to a GPCR protein, human endothelin receptor type B (hETB). GA-mD-VcMD is a generalized ensemble method that produces a free-energy landscape of the ligand-receptor binding by searching large-scale motions accompanied with stable maintenance of the fragile cell-membrane structure. All molecular components (bosentan, hETB, membrane, and solvent) were represented with an all-atom model. Then sampling was conducted from conformations where bosentan was distant from the binding site in the hETB binding pocket. The deepest basin in the resultant free-energy landscape was assigned to native-like complex conformation. The following binding mechanism was inferred. First, bosentan fluctuating randomly in solution is captured using a tip region of the flexible N-terminal tail of hETB via nonspecific attractive interactions (fly casting). Bosentan then slides occasionally from the tip to the root of the N-terminal tail (ligand–sliding). During this sliding, bosentan passes the gate of the binding pocket from outside to inside of the pocket with an accompanying rapid reduction of the molecular orientational variety of bosentan (orientational selection). Last, in the pocket, ligand–receptor attractive native contacts are formed. Eventually, the native-like complex is completed. The bosentan-captured conformations by the tip-region and root-region of the N-terminal tail correspond to two basins in the free-energy landscape. The ligand-sliding corresponds to overcoming of a free-energy barrier between the basins.
Mapping and understanding of correlated electroencephalogram (EEG) responses to the newsvendor problem
Authors: Truong Nghi Cong Dung , Wang Xinlong , Wanniarachchi Hashini , Lang Yan , Nerur Sridhar , Chen Kay-Yut , Liu Hanli
Published: August 2022

Decision-making is one of the most critical activities of human beings. To better understand the underlying neurocognitive mechanism while making decisions under an economic context, we designed a decision-making paradigm based on the newsvendor problem (NP) with two scenarios: low-profit margins as the more challenging scenario and high-profit margins as the less difficult one. The EEG signals were acquired from healthy humans while subjects were performing the task. We adopted the Correlated Component Analysis (CorrCA) method to identify linear combinations of EEG channels that maximize the correlation across subjects ($$n=23$$

n
=
23

) or trials ($$n=40$$

n
=
40

). The inter-subject or inter-trial correlation values (ISC or ITC) of the first three components were estimated to investigate the modulation of the task difficulty on subjects’ EEG signals and respective correlations. We also calculated the alpha- and beta-band power of the projection components obtained by the CorrCA to assess the brain responses across multiple task periods. Finally, the CorrCA forward models, which represent the scalp projections of the brain activities by the maximally correlated components, were further translated into source distributions of underlying cortical activity using the exact Low Resolution Electromagnetic Tomography Algorithm (eLORETA). Our results revealed strong and significant correlations in EEG signals among multiple subjects and trials during the more difficult decision-making task than the easier one. We also observed that the NP decision-making and feedback tasks desynchronized the normalized alpha and beta powers of the CorrCA components, reflecting the engagement state of subjects. Source localization results furthermore suggested several sources of neural activities during the NP decision-making process, including the dorsolateral prefrontal cortex, anterior PFC, orbitofrontal cortex, posterior cingulate cortex, and somatosensory association cortex.
Genomic epidemiological analysis of Klebsiella pneumoniae from Portuguese hospitals reveals insights into circulating antimicrobial resistance
Authors: Spadar Anton , Phelan Jody , Elias Rita , Modesto Ana , Caneiras Cátia , Marques Cátia , Lito Luís , Pinto Margarida , Cavaco-Silva Patrícia , Ferreira Helena , Pomba Constança , Da Silva Gabriela J. , Saavedra Maria José , Melo-Cristino José , Duarte Aida , Campino Susana , Perdigão João , Clark Taane G.
Published: August 2022

Klebsiella pneumoniae (Kp) bacteria are an increasing threat to public health and represent one of the most concerning pathogens involved in life-threatening infections and antimicrobial resistance (AMR). To understand the epidemiology of AMR of Kp in Portugal, we analysed whole genome sequencing, susceptibility testing and other meta data on 509 isolates collected nationwide from 16 hospitals and environmental settings between years 1980 and 2019. Predominant sequence types (STs) included ST15 (n = 161, 32%), ST147 (n = 36, 7%), ST14 (n = 26, 5%) or ST13 (n = 26, 5%), while 31% of isolates belonged to STs with fewer than 10 isolates. AMR testing revealed widespread resistance to aminoglycosides, fluoroquinolones, cephalosporins and carbapenems. The most common carbapenemase gene was blaKPC-3. Whilst the distribution of AMR linked plasmids appears uncorrelated with ST, their frequency has changed over time. Before year 2010, the dominant plasmid group was associated with the extended spectrum beta-lactamase gene blaCTX-M-15, but this group appears to have been displaced by another carrying the blaKPC-3 gene. Co-carriage of blaCTX-M and blaKPC-3 was uncommon. Our results from the largest genomics study of Kp in Portugal highlight the active transmission of strains with AMR genes and provide a baseline set of variants for future resistance monitoring and epidemiological studies.
Characteristics of choroidal neovascularization in elderly eyes with high myopia not meeting the pathologic myopia definition
Authors: Sayanagi Kaori , Fujimoto Satoko , Hara Chikako , Fukushima Yoko , Kawasaki Ryo , Sato Shigeru , Sakaguchi Hirokazu , Nishida Kohji
Published: August 2022

The META-Analysis of Pathologic Myopia Study group proposed a new classification system for myopic maculopathy (MM) with pathologic myopia (PM) defined as MM equal to/more serious than diffuse atrophy or the presence of plus lesions and myopic choroidal neovascularization (mCNV) defined as CNV in the eye with PM. However, CNV in elderly eyes with high myopia (HM) not meeting the PM definition (high-myopia CNV) are not classified as age-related macular degeneration (nAMD) or mCNV. This retrospective study included 39 eyes with high-myopia CNV, 20 eyes with mCNV, and 20 eyes with AMD. All patients were at least 40 years old. We compared the clinical characteristics and treatment outcomes among three groups. The high-myopia CNV group had significantly more CNV types, shorter axial length and fewer lacquer cracks (P < 0.0001, respectively); larger baseline greatest linear dimension (P = 0.0002), more fellow-eye drusen (P = 0.0106), more men (P = 0.0029), and more treatments (24 months, P = 0.0098) compared to the mCNV group. Compared with the nAMD group, the high-myopia CNV group was significantly younger (P = 0.0041), and had fewer CNV types (P = 0.0316), more lacquer cracks (P = 0.0079) and fewer drusen (affected-eye, P = 0.0006 and fellow-eye, P = 0.0222), and fewer treatments (24 months, P = 0.0030). Because the CNV in elderly eyes with HM not meeting the PM definition is classified as combined mCNV and nAMD, the clinical and angiographic findings are critical to determine the treatment strategy.