bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Influencing Monkeypox Vaccination: A Cue to Policy Implementation
Authors: Rajkhowa Priyobrat , Dsouza Viola Savy , Kharel Rashmi , Cauvery K. , Mallya B. Rashmi , Raksha D. S. , Mrinalini V. , Sharma Preejana , Pattanshetty Sanjay , Narayanan Prakash , Lahariya Chandrakant , Brand Helmut
Published: April 2023

Background

Following the mpox 2022 outbreak, several high-income countries have developed plans with inclusion criteria for vaccination against the mpox disease. This study was carried out to map the factors influencing mpox vaccination uptake to help address the challenges and increase vaccination confidence.

Methods

This was a study based on Tweet analysis. The VADER, Text Blob, and Flair analyzers were adopted for sentiment analysis. The “Levesque conceptual framework for healthcare access” was adopted to evaluate the factors impacting access and the decision to get mpox vaccination. Consolidated Criteria for Reporting Qualitative Research (COREQ) criteria were adopted.

Findings

A total of 149,133 tweets were extracted between 01/05/2022 and 23/09/2022. Around 1% of the random tweets were used for qualitative analysis. Of the 149,113, tweets were classified as positive, negative and neutral, respectively, by (a) VADER: (55,040) 37.05%, (44,395) 29.89%, and (49,106) 33.06%, (b) TextBlob: (70,900) 47.73%, (22,729) 15.30%, and (54,921) 36.97%, and (c) Flair: (31,389) 21.13%, (117,152) 78.87%, and 0.00%. Sentiment trajectories revealed that communication, stigmatization, accessibility to and availability of vaccines, and concerns about vaccine safety as factors influencing decision-making in the content and flow of tweets.

Interpretation

Twitter is a key surveillance tool for understanding factors influencing decisions and access to mpox vaccination. To address vaccine mistrust and disinformation, a social media-based risk communication plan must be devised. Adopting measures to remove logistical vaccination hurdles is needed. Obtaining fact-based information from credible sources is key to improving public confidence.
Illnesses and Injuries at a Remote American Residential Summer Camp Over 3 Seasons
Authors: Schlaudecker Jeffrey , Milligan Kevin J. , Glankler Erin , Pagan Angel , Weller Andrew M. , Cohn William
Published: April 2023

Introduction

Residential and wilderness excursion summer camps are safe, but outdoor activities can lead to injuries. The frequency of various illnesses and injuries at summer camps has been incompletely described. The treatments provided and the need for escalation to higher levels of care are variable.

Methods

A retrospective cohort analysis was conducted for all visits to a camp infirmary over 3 seasons at a residential summer camp in Minnesota. Seventeen descriptive categories of chief complaints and 13 categories of treatment disposition were created for all 695 eligible infirmary visits. The frequency and illness type for which escalation to a higher level of care beyond the camp infirmary was needed were reviewed.

Results

Four hundred one campers sought medical care 695 times over 3 seasons. The most common chief complaints were related to skin (35%), musculoskeletal injury (17%), and upper-respiratory symptoms (15%). The most common treatment and dispositions were over-the-counter medications (43%) and simple bandage or dressing (19%). Escalation of care to a clinic or emergency room was uncommon, with 35 (5%) infirmary visits requiring escalation. Musculoskeletal injuries were the most common reason for escalations of care. While overall less common than musculoskeletal injury, dental injury almost always resulted in escalation of care.

Conclusions

An analysis of 3 y of visits to a summer camp infirmary was used by camp medical staff to update protocols and obtain new supplies for diagnosis and treatments. A more complete understanding of the prevalence of injuries and illnesses has the potential to allow better preparation for camp medical staff.
The Life Worth Living in Ancient Greek and Roman Philosophy
Authors: Machek David
Published: April 2023

The account of the best life for humans – i.e. a happy or flourishing life – and what it might consist of was the central theme of ancient ethics. But what does it take to have a life that, if not happy, is at least worth living, compared with being dead or never having come into life? This question was also much discussed in antiquity, and David Machek's book reconstructs, for the first time, philosophical engagements with the question from Socrates to Plotinus. Machek's comprehensive book explores ancient views on a life worth living against a background of the pessimistic outlook on the human condition which was adopted by the Greek poets, and also shows the continuities and contrasts between the ancient perspective and modern philosophical debates about biomedical ethics and the ethics of procreation. His rich study of this relatively neglected theme offers a fresh and compelling narrative of ancient ethics.
Frictional Properties and Rheological Structure at the Ecuadorian Subduction Zone Revealed by the Postseismic Deformation Due To the 2016 Mw 7.8 Pedernales (Ecuador) Earthquake
Authors: Tian Zhen , Freymueller Jeffrey T. , Yang Zhiqiang , Li Zhenhong , Sun Heping
Published: April 2023

Postseismic deformation following subduction earthquakes includes the combined effects of afterslip surrounding the coseismic rupture areas and viscoelastic relaxation in the asthenosphere and provides unique and valuable information for understanding the rheological structure. Because the two postseismic mechanisms are usually spatiotemporally intertwined, we developed an integrated model combining their contributions, based on 5 years of observations following the 2016 Pedernales (Ecuador) earthquake. The results show that the early, near‐field postseismic deformation is dominated by afterslip, both updip and downdip of the coseismic rupture, and requires heterogeneous interface frictional properties. Viscoelastic relaxation contributes more to far‐field displacements at later time periods. The best‐fit integrated model favors a 45‐km thick lithosphere overlying a Burgers body viscoelastic asthenosphere with a Maxwell viscosity of 3 × 1019 Pa s (0.9–5 × 1019 Pa s at 95% confidence), assuming the Kelvin viscosity equal to 10% of that value. In addition to the postseismic afterslip, the coastal displacement of sites north and south of the rupture clearly require extra slip in the plate motion direction due to slow slip events that may be triggered by the coseismic stress changes (CSC) but are not purely driven by the CSC. Spatially variable afterslip following the Pedernales event, combined with the SSEs during the interseismic period, demonstrate that spatial frictional variability persists throughout the whole earthquake cycle. The interaction of adjacent fault patches with heterogeneous properties may contribute to the clustered large earthquakes in this area.
Extent of the Impact of Arctic Atmospheric Uncertainty on Extended‐Range Forecasting of Cold Events in East Asia
Authors: Han Zhe , Dai Guokun , Mu Mu , Li Chunxiang , Li Shuanglin , Ma Xueying , Zhu Mengbin
Published: April 2023

The extended‐range predictability of three simulated extreme cold events in East Asia in the Community Atmosphere Model (version 4) control experiment, whose atmospheric circulation backgrounds are similar to two recent observational cases, is investigated. The results show that they have a predictability of four pentads. Then, we evaluate the extent of the forecast uncertainty in the 4th pentad caused by the initial atmospheric uncertainties in the Arctic, which are large due to sparse instrumental observations. The initial uncertainty leading to the largest forecast uncertainty is obtained by the conditional nonlinear optimal perturbation method, and referred to as the CNOP‐type initial uncertainty. The forecast of the cold surge in the 4th pentad fails after adding the CNOP‐type initial uncertainty at day 0. In comparison, the forecast uncertainties are much weaker when the initial conditions are perturbed by noises, and the weaker influence may be due to the noises' lack of spatial structure. In terms of how the CNOP‐type initial uncertainty develops, a baroclinic structure is seen in the uncertainties on the first 2 days, followed by a propagating Rossby wave feature from the 2nd pentad to the 4th pentad. Meanwhile, synoptic transient eddy feedback also plays an essential role. The results suggest that the CNOP‐type initial uncertainty has potential to identify sensitive areas for targeted observations; plus, it could serve as a member of ensemble initial perturbations, since it indicates the largest uncertainty growth.
Large Uncertainties in Precipitation Exert Considerable Impact on Land Surface Temperature Modeling Over the Tibetan Plateau
Authors: Ma Xiaogang , Tian Lei , Jiang Yaozhi , Liang Jiguang , Tian Jiaxin , Zhou Jianhong , Shao Changkun , Yang Kun
Published: April 2023

The performance of land surface temperature (LST) simulations in land surface models is subject to uncertainties in atmospheric forcing datasets. However, the contributions of forcing variables in different datasets to the simulated LST over the Tibetan Plateau (TP) remain unclear. To investigate the sensitivity of LST simulation to atmospheric forcing, we conducted a series of experiments using the Community Land Model (CLM5.0) with different forcing datasets. Results showed that the simulated LST displayed large spatiotemporal variations, and the simulation driven by the China Meteorological Forcing Data set produced more reasonable estimates than the other simulations. Sensitivity analysis suggests that the 1% increase in air temperature causes the largest variation in LST (0.54%), while the same percentage change in precipitation leads to the smallest (only 0.002%) LST variation. However, the actual uncertainty in precipitation is much larger than that in air temperature, and thus uncertainty in precipitation contributes 24% of the LST variability in the cold season, compared to 18% for air temperature. Large precipitation uncertainty leads to strong uncertainties in snow processes (snowfall and snow cover fraction), and hence strong uncertainties in surface albedo and ground absorbed shortwave radiation, further exerting the absolute impact on LST in cold season. Moreover, the snowfall is also influenced by different schemes of snowfall/rainfall partitioning. This may result in uncertainties in snowfall and consequently LST for the southeastern TP. Our study highlights the importance of high‐quality precipitation data, a forcing variable usually ignored in previous studies of LST simulation on the TP.
The Influences of the Multi‐Scale Sea Surface Temperature Anomalies in the North Pacific on the Jet Stream in Winter
Authors: Hu Haibo , Zhao Yihang , Yang Xiu‐Qun , Jiang Shunyu , Mao Kefeng , Bai Haokun
Published: April 2023

Using Climate Forecast System Reanalysis (CFSR) data and numerical simulations, the impacts of the multi‐scale sea surface temperature (SST) anomalies in the North Pacific on the boreal winter atmospheric circulations are investigated. The basin‐scale SST anomaly as the Pacific Decadal Oscillation (PDO) pattern, a narrow meridional band of frontal‐scale smoothed SST anomaly in the subtropical front zone (STFZ) and the spatial dispersed eddy‐scale SST anomalies within the STFZ are the three types of forcings. The results of statistical methods find that all three oceanic forcings may correspond to the winter North Pacific jet changing with the similar pattern. Furthermore, several atmospheric general circulation model simulations are used to reveal the differences and detail processes of the three forcings. The basin‐scale cold PDO‐pattern SST anomaly first causes negative turbulent heat flux anomalies, atmospheric cooling, and wind deceleration in the lower atmosphere. Subsequently, the cooling temperature with an amplified southern lower temperature gradient and baroclinity brings a lagging middle warming because of the enhanced atmospheric eddy heat transport. The poleward and upward development of baroclinic fluctuations eventually causes the acceleration of the upper jet. The smoothed frontal‐ and eddy‐scales SST anomalies in the STFZ cause comparable anomalous jet as the basin‐scale by changing the upward baroclinic energy and Eliassen‐Palm fluxes. The forcing effects of multi‐scales SST anomalies coexist simultaneously in the mid‐latitude North Pacific, which can cause similar anomalous upper atmospheric circulations. This is probably why it is tricky to define the certain oceanic forcing to the specific observed atmospheric circulation variation.
Toward Emulating an Explicit Organic Chemistry Mechanism With Random Forest Models
Authors: Mouchel‐Vallon Camille , Hodzic Alma
Published: April 2023

Predicting secondary organic aerosol (SOA) formation relies either on extremely detailed, numerically expensive models accounting for the condensation of individual species or on extremely simplified, numerically affordable models parameterizing SOA formation for large‐scale simulations. In this work, we explore the possibility of creating a random forest to reproduce the behavior of a detailed atmospheric organic chemistry model at a fraction of the numerical cost. A comprehensive data set was created based on thousands of individual detailed simulations, randomly initialized to account for the variety of atmospheric chemical environments. Recurrent random forests were trained to predict organic matter formation from dodecane and toluene precursors, and the partitioning between gas and particle phases. Validation tests show that the random forests perform well without any divergence over 10 days of simulations. The distribution of errors shows that the sampling of initial conditions for the training simulations needs to focus on chemical regimes where SOA production is the most sensitive. Sensitivity tests show that specializing multiple random forests for a specific chemical regime is not more efficient than training a single general random forest for the entire data set. The most important predictors are those providing information about the chemical regime, oxidants levels, and existing organic mass. The choice of predictors is crucial as using too many unimportant predictors reduces the performances of the random forests.
Orbital Characterization of the Composition and Distribution of Spinels Across the Crisium Region: Insight From Luna 20 Samples
Authors: Moriarty D. P. , Simon S. B. , Shearer C. K. , Haggerty S. E. , Petro N. , Li Shuai
Published: April 2023

Spinels represent a small fraction of lunar surface materials but provide important insights into the petrological evolution of the lunar crust and mantle. Previous remote sensing analyses of highlands spinel‐bearing lithologies have focused on pure Mg‐Al spinels, which are rare in the lunar sample collection. Using Moon Mineralogy Mapper data, we develop and test an approach for detecting spectral signatures of spinel across a wider range of Mg, Al, Fe, Cr, Ti‐bearing compositions than have been addressed in previous studies, including within mafic‐bearing assemblages. This approach is validated through integration with laboratory‐measured spinel spectra and petrographic observations of samples returned by the Luna 20 mission from the Hilly and Furrowed Terrain surrounding the Crisium Basin. Applying this approach to data from the Crisium region, small abundances of spinel (<∼5 vol%) with a range of Mg, Al, Fe, Cr, and Ti content and petrologic origin (inferred from Luna 20 samples) were found to be widespread within highlands soils across the Crisium region. This result diverges from previous remote sensing analyses, which only reported small, isolated exposures of pure Mg‐Al spinel (as well as a possible detection of Fe, Cr‐bearing spinels localized within pyroclastic materials at Sinus Aestuum). Geologic associations of candidate spinel detections across this region are consistent with a shallow crustal origin rather than excavation from depth during the Crisium‐forming impact. These spinels are detectible in near‐infrared spectroscopic data, particularly in areas of low optical maturity and may influence the spectral continuum of highlands soils.
An Intercomparison of Large‐Eddy Simulations of a Convection Cloud Chamber Using Haze‐Capable Bin and Lagrangian Cloud Microphysics Schemes
Authors: Yang Fan , Hoffmann Fabian , Shaw Raymond A. , Ovchinnikov Mikhail , Vogelmann Andrew M.
Published: April 2023

Recent in situ observations show that haze particles exist in a convection cloud chamber. The microphysics schemes previously used for large‐eddy simulations of the cloud chamber could not fully resolve haze particles and the associated processes, including their activation and deactivation. Specifically, cloud droplet activation was modeled based on Twomey‐type parameterizations, wherein cloud droplets were formed when a critical supersaturation for the available cloud condensation nuclei (CCN) was exceeded and haze particles were not explicitly resolved. Here, we develop and adapt haze‐capable bin and Lagrangian microphysics schemes to properly resolve the activation and deactivation processes. Results are compared with the Twomey‐type CCN‐based bin microphysics scheme in which haze particles are not fully resolved. We find that results from the haze‐capable bin microphysics scheme agree well with those from the Lagrangian microphysics scheme. However, both schemes significantly differ from those from a CCN‐based bin microphysics scheme unless CCN recycling is considered. Haze particles from the recycling of deactivated cloud droplets can strongly enhance cloud droplet number concentration due to a positive feedback in haze‐cloud interactions in the cloud chamber. Haze particle size distributions are more realistic when considering solute and curvature effects that enable representing the complete physics of the activation process. Our study suggests that haze particles and their interactions with cloud droplets may have a strong impact on cloud properties when supersaturation fluctuations are comparable to mean supersaturation, as is the case in the cloud chamber and likely is the case in the atmosphere, especially in polluted conditions.
Climate Change, Megafires Crush Forest Regeneration
Authors: Averett Nancy
Published: April 2023

High-intensity fires in western states kill mature trees and their seeds while warmer, drier conditions stress seedlings. But forest managers can still intervene to change this trajectory.
Exoplanets May Support Life in the Terminator Zone
Authors: Dasgupta Alakananda
Published: April 2023

A new study finds that the intersection between a searing dayside and a freezing nightside could be habitable.
Interplanetary Magnetic Field By Controls the Magnetopause Location
Authors: Aghabozorgi Nafchi M. , Němec F. , Pi G. , Němeček Z. , Šafránková J. , Grygorov K. , Šimůnek J.
Published: April 2023

We present a statistical study of interplanetary magnetic field (IMF) effects on the magnetopause location based on nearly 15,000 magnetopause crossings identified in the THEMIS A‐E, Magion 4, Geotail, and Interball‐1 satellite data. In order to exclude the dominant controlling role of the solar wind dynamic pressure, differences between observed and empirical model magnetopause distances are analyzed. We find that the magnetopause distance is significantly controlled by the IMF clock angle, not considered in the used empirical models. Furthermore, during very low Alfvén Mach numbers (MA < 4), IMF By component can induce a considerable dawn‐dusk asymmetry of the magnetopause shape. The magnetopause distance is found to be larger in the direction of the IMF vector, that is, not only the magnitude but also the orientation of the IMF By component is eventually important. The obtained results are qualitatively consistent with a magnetohydrodynamic model run at the Community Coordinated Modeling Center.
Spatial single cell analysis of tumor microenvironment remodeling pattern in primary central nervous system lymphoma
Authors: Xia Yuan , Sun Tao , Li Guosheng , Li Mingying , Wang Dongmei , Su Xiuhua , Ye Jingjing , Ji Chunyan
Published: April 2023

To determine the overall tumor microenvironment (TME), characteristics, and transition mechanisms in primary central nervous system lymphoma (PCNSL), we performed spatial transcriptomics and matched the corresponding single-cell sequencing data of PCNSL patients. We found that tumor cells may achieve a “TME remodeling pattern” through an “immune pressure-sensing model”, in which they could choose to reshape the TME into a barrier environment or a cold environment according to the immune pressure. A key FKBP5+ tumor subgroup was found to be responsible for pushing tumors into the barrier environment, which provides a possible way to evaluate the stage of PCNSL. The specific mechanism of the TME remodeling pattern and the key molecules of the immune pressure-sensing model were identified through the spatial communication analysis. Finally, we discovered the spatial and temporal distributions and variation characteristics of immune checkpoint molecules and CAR-T target molecules in immunotherapy. These data clarified the TME remodeling pattern of PCNSL, provided a reference for its immunotherapy, and provided suggestions for the TME remodeling mechanism of other cancers.
Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment
Authors: Granot-Hershkovitz Einat , Spitzer Brian , Yang Yunju , Tarraf Wassim , Yu Bing , Boerwinkle Eric , Fornage Myriam , Mosley Thomas H. , DeCarli Charles , Kristal Bruce S. , González Hector M. , Sofer Tamar
Published: April 2023

We studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)—the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed their association with MCI in datasets of diverse race/ethnicities. We first performed a GWAS for the MCI-MRS and BAIBA, in Hispanic/Latino adults (n = 3890) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We identified ten independent genome-wide significant (pvalue <5 × 10−8) variants associated with MCI-MRS or BAIBA. Variants associated with the MCI-MRS are located in the Alanine-Glyoxylate Aminotransferase 2 (AGXT2gene), which is known to be associated with BAIBA metabolism. Variants associated with BAIBA are located in theAGXT2gene and in theSLC6A13gene. Next, we tested the variants’ association with MCI in independent datasets ofn = 3178 HCHS/SOL older individuals,n = 3775 European Americans, andn = 1032 African Americans from the Atherosclerosis Risk In Communities (ARIC) study. Variants were considered associated with MCI if theirpvalue <0.05 in the meta-analysis of the three datasets and their direction of association was consistent with expectation. Rs16899972 and rs37369 from theAGXT2region were associated with MCI. Mediation analysis supported the mediation effect of BAIBA between the two genetic variants and MCI (pvalue = 0.004 for causal mediated effect). In summary, genetic variants in theAGXT2region are associated with MCI in Hispanic/Latino, African, and European American populations in the USA, and their effect is likely mediated by changes in BAIBA levels.
Artificial intelligence approach for the analysis of placebo-controlled clinical trials in major depressive disorders accounting for individual propensity to respond to placebo
Authors: Gomeni Roberto , Bressolle-Gomeni Françoise , Fava Maurizio
Published: April 2023

Treatment effect in clinical trials for major depressive disorders (RCT) can be viewed as the resultant of treatment specific and non-specific effects. Baseline individual propensity to respond non-specifically to any treatment or intervention can be considered as a major non-specific confounding effect. The greater is the baseline propensity, the lower will be the chance to detect any treatment-specific effect. The statistical methodologies currently applied for analyzing RCTs doesn’t account for potential unbalance in the allocation of subjects to treatment arms due to heterogenous distributions of propensity. Hence, the groups to be compared may be imbalanced, and thus incomparable. Propensity weighting methodology was used to reduce baseline imbalances between arms. A randomized, double-blind, placebo controlled, three arms, parallel group, 8-week, fixed-dose study to evaluate efficacy of paroxetine CR 12.5 and 25 mg/day is presented as a cases study. An artificial intelligence model was developed to predict placebo response at week 8 in subjects assigned to placebo arm using changes from screening to baseline of individual Hamilton Depression Rating Scale items. This model was used to predict the probability to respond to placebo in each subject. The inverse of the probability was used as weight in the mixed-effects model applied to assess treatment effect. The analysis with and without propensity weight indicated that the weighted analysis provided an estimate of treatment effect and effect-size about twice larger than the non-weighted analysis. Propensity weighting provides an unbiased strategy to account for heterogeneous and uncontrolled placebo effect making patients’ data comparable across treatment arms.
Facilitating dental disease screening program in prisoners using an intraoral camera in teledentistry
Authors: Santipipat Charnchai , Kaewkamnerdpong Issarapong , Limpuangthip Nareudee
Published: April 2023

Objectives

To facilitate dental disease screening program in prisoners by testing the diagnostic accuracy of teledentistry examination in comparison to direct oral examination by a dentist.

Materials and methods

This crossover study comprised three phases. Phase I, prisoner health volunteers (PHVs) enrolled teledentistry training for an intraoral camera (IOC) use. Phase II, the PHV used IOC for examining dental diseases of prisoners who reported dental-related problems, and captured symptomatic areas. The PHV and dentist independently determined tentative dental treatment need, comprising dental fillings, scaling, extraction, and surgical removal of impacted tooth. Phase III, another dentist performed direct oral examination of the prisoners who reported problems in phase II and determined dental treatment needs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, using direct oral examination by dentist as a true positive.

Results

Diagnostic accuracy was determined in 152 prisoners with 215 teeth. Sensitivity, specificity, PPV, and NPV of teledentistry and direct examination between two dentists were above 80%. The lowest sensitivity and specificity of teledentistry examination by the PHV were scaling and surgical removal.

Conclusions

IOC use in teledentistry facilitates dentists in dental diseases screening for prisoners with acceptable diagnostic accuracy in identifying possible treatment needs. However, the imaging obtained from teledentistry is not adequate to accurately identify all dental treatment needs.
Integrated circulating tumour DNA and cytokine analysis for therapy monitoring of ALK-rearranged lung adenocarcinoma
Authors: Angeles Arlou Kristina , Janke Florian , Daum Ann-Kathrin , Reck Martin , Schneider Marc A. , Thomas Michael , Christopoulos Petros , Sültmann Holger
Published: April 2023

Background

Detection of circulating tumour DNA (ctDNA) in biological fluids is a minimally invasive alternative to tissue biopsy for therapy monitoring. Cytokines are released in the tumour microenvironment to influence inflammation and tumorigenic mechanisms. Here, we investigated the potential biomarker utility of circulating cytokines vis-à-vis ctDNA in ALK-rearranged+ lung adenocarcinoma (ALK + NSCLC) and explored the optimal combination of molecular parameters that could indicate disease progression.

Methods

Longitudinal serum samples (n = 296) were collected from ALK + NSCLC patients (n = 38) under tyrosine kinase inhibitor (TKI) therapy and assayed to quantify eight cytokines: IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, MCP1 and TNF-α. Generalised linear mixed-effect modelling was performed to test the performance of different combinations of cytokines and previously determined ctDNA parameters in identifying progressive disease.

Results

Serum IL-6, IL-8 and IL-10 were elevated at progressive disease, with IL-8 having the most significant impact as a biomarker. Integrating changes in IL-8 with ctDNA parameters maximised the performance of the classifiers in identifying disease progression, but this did not significantly outperform the model based on ctDNA alone.

Conclusions

Serum cytokine levels are potential disease progression markers in ALK + NSCLC. Further validation in a larger and prospective cohort is necessary to determine whether the addition of cytokine evaluation could improve current tumour monitoring modalities in the clinical setting.
Anticipating changes in the HER2 status of breast tumours with disease progression—towards better treatment decisions in the new era of HER2-low breast cancers
Authors: Bergeron Anthony , Bertaut Aurélie , Beltjens Françoise , Charon-Barra Céline , Amet Alix , Jankowski Clémentine , Desmoulins Isabelle , Ladoire Sylvain , Arnould Laurent
Published: April 2023

Background

HER2 expression is often negative or low in primary breast cancers (BCs) but its changes with disease progression remain poorly known. We aimed to estimate them between primary and recurrent tumours, and identify predictive factors.

Methods

We compared the HER2 status, and clinical and pathological characteristics by its evolution category (stable or changed), between all primary BCs and matched recurrences registered in our database in 2000–2020 (n = 512).

Results

HER2-low tumours were the most prevalent at diagnosis (44.9%), followed by HER2-negative tumours (39.3%). HER2 status significantly changed in 37.3% of recurrences, mainly of HER2-negative and HER2-low tumours. HER2-negative tumours which relapsed as HER2-low significantly more frequently expressed oestrogen receptors (ER) and recurred later than stably HER2-negative tumours. Changed HER2 status in distant metastases correlated with lower proliferation rates and higher ER expression in primary tumours, and among metastases of hormone receptor-positive (HR+) tumours—with weak progesterone receptor (PR) expression in primary tumours.

Conclusions

HER2 status changes with BC progression, with enrichment of HER2-low tumours in advanced stages. The ER+/PR− status, low proliferation index and time to late recurrence correlated with these changes. These findings highlight the need of retesting recurrences, especially of HR + primary tumours, to identify candidates for new anti-HER2 therapies.
Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M
Authors: Poggio Elena , Vallese Francesca , Hartel Andreas J. W. , Morgenstern Travis J. , Kanner Scott A. , Rauh Oliver , Giamogante Flavia , Barazzuol Lucia , Shepard Kenneth L. , Colecraft Henry M. , Clarke Oliver Biggs , Brini Marisa , Calì Tito
Published: April 2023

Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO). As of February 2023, almost 670 million cases and 6,8 million deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain a single-stranded RNA genome enclosed in a viral capsid consisting of four structural proteins: the nucleocapsid (N) protein, in the ribonucleoprotein core, the spike (S) protein, the envelope (E) protein, and the membrane (M) protein, embedded in the surface envelope. In particular, the E protein is a poorly characterized viroporin with high identity amongst all the β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) and a low mutation rate. Here, we focused our attention on the study of SARS-CoV-2 E and M proteins, and we found a general perturbation of the host cell calcium (Ca2+) homeostasis and a selective rearrangement of the interorganelle contact sites. In vitro and in vivo biochemical analyses revealed that the binding of specific nanobodies to soluble regions of SARS-CoV-2 E protein reversed the observed phenotypes, suggesting that the E protein might be an important therapeutic candidate not only for vaccine development, but also for the clinical management of COVID designing drug regimens that, so far, are very limited.
Oligomeric states of ASC specks regulate inflammatory responses by inflammasome in the extracellular space
Authors: Yu Tae-Geun , Cha Jeong Seok , Kim Gijeong , Sohn Yoo-Kyoung , Yoo Youngki , Kim Uijin , Song Ji-Joon , Cho Hyun-Soo , Kim Hak-Sung
Published: April 2023

Inflammasomes are multi-protein complexes and play a crucial role in host defense against pathogens. Downstream inflammatory responses through inflammasomes are known to be related to the oligomerization degree of ASC specks, but the detailed mechanism still remains unexplored. Here, we demonstrate that oligomerization degrees of ASC specks regulate the caspase-1 activation in the extracellular space. A protein binder specific for a pyrin domain (PYD) of ASC (ASCPYD) was developed, and structural analysis revealed that the protein binder effectively inhibits the interaction between PYDs, disassembling ASC specks into low oligomeric states. ASC specks with a low oligomerization degree were shown to enhance the activation of caspase-1 by recruiting and processing more premature caspase-1 through interactions between CARD of caspase-1 (caspase-1CARD) and CARD of ASC (ASCCARD). These findings can provide insight into controlling the inflammasome-mediated inflammatory process as well as the development of inflammasome-targeting drugs.
Zero-field quantum beats and spin decoherence mechanisms in CsPbBr3 perovskite nanocrystals
Authors: Cai Rui , Wadgaonkar Indrajit , Lim Jia Wei Melvin , Dal Forno Stefano , Giovanni David , Feng Minjun , Ye Senyun , Battiato Marco , Sum Tze Chien
Published: April 2023

Coherent optical manipulation of exciton states provides a fascinating approach for quantum gating and ultrafast switching. However, their coherence time for incumbent semiconductors is highly susceptible to thermal decoherence and inhomogeneous broadening effects. Here, we uncover zero-field exciton quantum beating and anomalous temperature dependence of the exciton spin lifetimes in CsPbBr3 perovskite nanocrystals (NCs) ensembles. The quantum beating between two exciton fine-structure splitting (FSS) levels enables coherent ultrafast optical control of the excitonic degree of freedom. From the anomalous temperature dependence, we identify and fully parametrize all the regimes of exciton spin depolarization, finding that approaching room temperature, it is dominated by a motional narrowing process governed by the exciton multilevel coherence. Importantly, our results present an unambiguous full physical picture of the complex interplay of the underlying spin decoherence mechanisms. These intrinsic exciton FSS states in perovskite NCs present fresh opportunities for spin-based photonic quantum technologies.
Single-cell metabolic fingerprints discover a cluster of circulating tumor cells with distinct metastatic potential
Authors: Zhang Wenjun , Xu Feifei , Yao Jiang , Mao Changfei , Zhu Mingchen , Qian Moting , Hu Jun , Zhong Huilin , Zhou Junsheng , Shi Xiaoyu , Chen Yun
Published: April 2023

Circulating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the “best” indicator of metastatic risk because their heterogeneity is generally neglected. In this study, we develop a molecular typing system to predict colorectal cancer metastasis potential based on the metabolic fingerprints of single CTCs. After identification of the metabolites potentially related to metastasis using mass spectrometry-based untargeted metabolomics, setup of a home-built single-cell quantitative mass spectrometric platform for target metabolite analysis in individual CTCs and use of a machine learning method composed of non-negative matrix factorization and logistic regression, CTCs are divided into two subgroups, C1 and C2, based on a 4-metabolite fingerprint. Both in vitro and in vivo experiments demonstrate that CTC count in C2 subgroup is closely associated with metastasis incidence. This is an interesting report on the presence of a specific population of CTCs with distinct metastatic potential at the single-cell metabolite level.
Electrosynthesis of chlorine from seawater-like solution through single-atom catalysts
Authors: Liu Yangyang , Li Can , Tan Chunhui , Pei Zengxia , Yang Tao , Zhang Shuzhen , Huang Qianwei , Wang Yihan , Zhou Zheng , Liao Xiaozhou , Dong Juncai , Tan Hao , Yan Wensheng , Yin Huajie , Liu Zhao-Qing , Huang Jun , Zhao Shenlong
Published: April 2023

The chlor-alkali process plays an essential and irreplaceable role in the modern chemical industry due to the wide-ranging applications of chlorine gas. However, the large overpotential and low selectivity of current chlorine evolution reaction (CER) electrocatalysts result in significant energy consumption during chlorine production. Herein, we report a highly active oxygen-coordinated ruthenium single-atom catalyst for the electrosynthesis of chlorine in seawater-like solutions. As a result, the as-prepared single-atom catalyst with Ru-O4moiety (Ru-O4SAM) exhibits an overpotential of only ~30 mV to achieve a current density of 10 mA cm−2in an acidic medium (pH = 1) containing 1 M NaCl. Impressively, the flow cell equipped with Ru-O4SAM electrode displays excellent stability and Cl2selectivity over 1000 h continuous electrocatalysis at a high current density of 1000 mA cm−2. Operando characterizations and computational analysis reveal that compared with the benchmark RuO2electrode, chloride ions preferentially adsorb directly onto the surface of Ru atoms on Ru-O4SAM, thereby leading to a reduction in Gibbs free-energy barrier and an improvement in Cl2selectivity during CER. This finding not only offers fundamental insights into the mechanisms of electrocatalysis but also provides a promising avenue for the electrochemical synthesis of chlorine from seawater electrocatalysis.
Preparing high-concentration individualized carbon nanotubes for industrial separation of multiple single-chirality species
Authors: Yang Dehua , Li Linhai , Li Xiao , Xi Wei , Zhang Yuejuan , Liu Yumin , Wei Xiaojun , Zhou Weiya , Wei Fei , Xie Sishen , Liu Huaping
Published: April 2023

Industrial production of single-chirality carbon nanotubes is critical for their applications in high-speed and low-power nanoelectronic devices, but both their growth and separation have been major challenges. Here, we report a method for industrial separation of single-chirality carbon nanotubes from a variety of raw materials with gel chromatography by increasing the concentration of carbon nanotube solution. The high-concentration individualized carbon nanotube solution is prepared by ultrasonic dispersion followed by centrifugation and ultrasonic redispersion. With this technique, the concentration of the as-prepared individualized carbon nanotubes is increased from about 0.19 mg/mL to approximately 1 mg/mL, and the separation yield of multiple single-chirality species is increased by approximately six times to the milligram scale in one separation run with gel chromatography. When the dispersion technique is applied to an inexpensive hybrid of graphene and carbon nanotubes with a wide diameter range of 0.8–2.0 nm, and the separation yield of single-chirality species is increased by more than an order of magnitude to the sub-milligram scale. Moreover, with present separation technique, the environmental impact and cost of producing single-chirality species are greatly reduced. We anticipate that this method promotes industrial production and practical applications of single-chirality carbon nanotubes in carbon-based integration circuits.
Recognition of an Ala-rich C-degron by the E3 ligase Pirh2
Authors: Wang Xiaolu , Li Yao , Yan Xiaojie , Yang Qing , Zhang Bing , Zhang Ying , Yuan Xinxin , Jiang Chenhao , Chen Dongxing , Liu Quanyan , Liu Tong , Mi Wenyi , Yu Ying , Dong Cheng
Published: April 2023

The ribosome-associated quality-control (RQC) pathway degrades aberrant nascent polypeptides arising from ribosome stalling during translation. In mammals, the E3 ligase Pirh2 mediates the degradation of aberrant nascent polypeptides by targeting the C-terminal polyalanine degrons (polyAla/C-degrons). Here, we present the crystal structure of Pirh2 bound to the polyAla/C-degron, which shows that the N-terminal domain and the RING domain of Pirh2 form a narrow groove encapsulating the alanine residues of the polyAla/C-degron. Affinity measurements in vitro and global protein stability assays in cells further demonstrate that Pirh2 recognizes a C-terminal A/S-X-A-A motif for substrate degradation. Taken together, our study provides the molecular basis underlying polyAla/C-degron recognition by Pirh2 and expands the substrate recognition spectrum of Pirh2.
Revised Minoan eruption volume as benchmark for large volcanic eruptions
Authors: Karstens Jens , Preine Jonas , Crutchley Gareth J. , Kutterolf Steffen , van der Bilt Willem G. M. , Hooft Emilie E. E. , Druitt Timothy H. , Schmid Florian , Cederstrøm Jan Magne , Hübscher Christian , Nomikou Paraskevi , Carey Steven , Kühn Michel , Elger Judith , Berndt Christian
Published: April 2023

Despite their global societal importance, the volumes of large-scale volcanic eruptions remain poorly constrained. Here, we integrate seismic reflection and P-wave tomography datasets with computed tomography-derived sedimentological analyses to estimate the volume of the iconic Minoan eruption. Our results reveal a total dense-rock equivalent eruption volume of 34.5 ± 6.8 km³, which encompasses 21.4 ± 3.6 km³ of tephra fall deposits, 6.9 ± 2 km³ of ignimbrites, and 6.1 ± 1.2 km³ of intra-caldera deposits. 2.8 ± 1.5 km³ of the total material consists of lithics. These volume estimates are in agreement with an independent caldera collapse reconstruction (33.1 ± 1.2 km³). Our results show that the Plinian phase contributed most to the distal tephra fall, and that the pyroclastic flow volume is significantly smaller than previously assumed. This benchmark reconstruction demonstrates that complementary geophysical and sedimentological datasets are required for reliable eruption volume estimates, which are necessary for regional and global volcanic hazard assessments.
Single-neuron mechanisms of neural adaptation in the human temporal lobe
Authors: Reber Thomas P. , Mackay Sina , Bausch Marcel , Kehl Marcel S. , Borger Valeri , Surges Rainer , Mormann Florian
Published: April 2023

A central function of the human brain is to adapt to new situations based on past experience. Adaptation is reflected behaviorally by shorter reaction times to repeating or similar stimuli, and neurophysiologically by reduced neural activity in bulk-tissue measurements with fMRI or EEG. Several potential single-neuron mechanisms have been hypothesized to cause this reduction of activity at the macroscopic level. We here explore these mechanisms using an adaptation paradigm with visual stimuli bearing abstract semantic similarity. We recorded intracranial EEG (iEEG) simultaneously with spiking activity of single neurons in the medial temporal lobes of 25 neurosurgical patients. Recording from 4917 single neurons, we demonstrate that reduced event-related potentials in the macroscopic iEEG signal are associated with a sharpening of single-neuron tuning curves in the amygdala, but with an overall reduction of single-neuron activity in the hippocampus, entorhinal cortex, and parahippocampal cortex, consistent with fatiguing in these areas.
Hydrogel dressing integrating FAK inhibition and ROS scavenging for mechano-chemical treatment of atopic dermatitis
Authors: Jia Yuanbo , Hu Jiahui , An Keli , Zhao Qiang , Dang Yang , Liu Hao , Wei Zhao , Geng Songmei , Xu Feng
Published: April 2023

Atopic dermatitis (AD) is a chronic skin disease caused by skin immune dyshomeostasis and accompanied by severe pruritus. Although oxidative stress and mechanical scratching can aggravate AD inflammation, treatment targeting scratching is often overlooked, and the efficiency of mechano-chemically synergistic therapy remains unclear. Here, we find that enhanced phosphorylation of focal adhesion kinase (FAK) is associated with scratch-exacerbated AD. We then develop a multifunctional hydrogel dressing that integrates oxidative stress modulation with FAK inhibition to synergistically treat AD. We show that the adhesive, self-healing and antimicrobial hydrogel is suitable for the unique scratching and bacterial environment of AD skin. We demonstrate that it can scavenge intracellular reactive oxygen species and reduce mechanically induced intercellular junction deficiency and inflammation. Furthermore, in mouse AD models with controlled scratching, we find that the hydrogel alleviates AD symptoms, rebuilds the skin barrier, and inhibits inflammation. These results suggest that the hydrogel integrating reactive oxygen species scavenging and FAK inhibition could serve as a promising skin dressing for synergistic AD treatment.
Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation
Authors: Yang Wei , Liu Li-Bo , Liu Feng-Liang , Wu Yan-Hua , Zhen Zi-Da , Fan Dong-Ying , Sheng Zi-Yang , Song Zheng-Ran , Chang Jia-Tong , Zheng Yong-Tang , An Jing , Wang Pei-Gang
Published: April 2023

Zika virus (ZIKV) is a potential threat to male reproductive health but the mechanisms underlying its influence on testes during ZIKV infection remain obscure. To address this question, we perform single-cell RNA sequencing using testes from ZIKV-infected mice. The results reveal the fragility of spermatogenic cells, especially spermatogonia, to ZIKV infection and show that the genes of the complement system are significantly upregulated mainly in infiltrated S100A4 + monocytes/macrophages. Complement activation and its contribution to testicular damage are validated by ELISA, RT‒qPCR and IFA and further verify in ZIKV-infected northern pigtailed macaques by RNA genome sequencing and IFA, suggesting that this might be the common response to ZIKV infection in primates. On this basis, we test the complement inhibitor C1INH and S100A4 inhibitors sulindac and niclosamide for their effects on testis protection. C1INH alleviates the pathological change in the testis but deteriorates ZIKV infection in general. In contrast, niclosamide effectively reduces S100A4 + monocyte/macrophage infiltration, inhibits complement activation, alleviates testicular damage, and rescues the fertility of male mice from ZIKV infection. This discovery therefore encourages male reproductive health protection during the next ZIKV epidemic.