bluuebunny/crossref_metadata_2025 huggingface dataset:
Sixteen-year trends in adolescent consumption of sugar-sweetened soda in six European countries with a soda tax and comparison countries: a repeated cross-sectional survey analysis
Authors: Chatelan Angeline , Rouche Manon , Dzielska Anna , Fismen Anne-Siri , Kelly Colette , Pedroni Camille , Desbouys Lucille , Castetbon Katia
Published: November 2022

Objective:

To examine changes in the proportions of daily, weekly and occasional consumers of sugar-sweetened soda in six European countries that introduced/updated a tax between 2001–2002 and 2017–2018 and in neighbouring comparison countries (without a tax).

Design:

Repeated cross-sectional surveys.

Setting:

Health Behaviour in School-aged Children study, spanning five survey years (school years 2001–2002 to 2017–2018).

Participants:

Nationally representative samples of 13-year- and 15-year-old adolescents (n 236 623, 51·0 % girls).

Results:

Tax sizes (€0·02/l to €0·22/l) and pre-tax soda consumption were heterogeneous across countries. Prevalence of daily soda consumption reduced in the survey year following tax implementation in Latvia (from 17·9 to 11·9 %, P = 0·01), Finland (4·2 to 2·5 %, P = 0·001), Belgium (35·1 to 27·8 %, P < 0·001) and Portugal (17·4 to 14·9 %, P = 0·02), but not in Hungary (29·8 to 31·3 %, P = 0·47) or France (29·4 to 28·2 %, P = 0·27). However, reductions were similar (Finland) or smaller (Belgium, Portugal) than those in the comparison countries, except in Latvia where the reduction was larger (Pinteraction < 0·001). Prevalence of weekly soda consumption remained stable (Finland, Hungary and France) or increased (Latvia, Belgium); only Portugal experienced a decline (P < 0·001), which was larger than in the comparison country (Pinteraction < 0·001). Prevalence of occasional soda consumption (<1x/week) did not rise after implementation of the tax in Latvia, Finland, Hungary, France or Belgium, or the rise was similar to the comparison country in Portugal (Pinteraction = 0·15).

Conclusions:

Countries with a soda tax did not experience larger beneficial changes in post-tax adolescent consumption frequency of soda than comparison countries. Further studies, with different taxation types, are needed in the adolescent population.
Competing visions: schooling the nation and the “revolt” at the Ockenden Tibetan school
Authors: Choedup Ugyan
Published: November 2022

This article examines the incident of a “revolt” in the Ockenden Tibetan refugee school in the early 1960s. By analyzing this previously unknown incident of “revolt” in the Tibetan refugee school within the broader historical context of early years in exile, this article aims to underline the contested and contingent process of nation-building in exile. I argue that the Ockenden incident, as forgotten fragments of the Tibetan past, provides us a rare glimpse into the early history of contestation over the production of national history and discourse on Tibet, where exiled Bonpos, a non-Buddhist minority, attempted to renegotiate their marginality by producing alternative history and discourse on Tibet. By focusing on the history of the Ockenden incident as a forgotten fragment from the exile Tibetan past, this article aims to decenter the teleology of Tibetan nationalism by bringing to light one of the unrealized alternative future agendas different groups of exiled Tibetans had in those early moments of discursive formation.
Factor Structure and Validity of the Suicidal Narrative Inventory Among Indian Adults
Authors: Menon Vikas , Bafna Anokhi Rajiv , Rogers Megan L. , Cohen Lisa J. , Richards Jenelle , Galynker Igor
Published: November 2022

Abstract: Background: The suicidal narrative is a presuicidal state comprising several risk factors for suicide and is assessed using the Suicidal Narrative Inventory (SNI). Aims To assess the internal structure, reliability, and validity of SNI among Indian adults. Methods Between August 2020 and January 2021, the SNI, together with other self-report measures, was administered to adult respondents using an online anonymized questionnaire. Confirmatory factor analysis (CFA) was carried out to test the factor structure of the SNI. Results Usable responses were obtained from 302 participants ( Mage = 43.5 ± 17.9 years, 53.6% female). The results of an eight-factor CFA of the SNI resulted in good model fit (χ2 [637] = 969.73, p < .001, comparative fit index = 1.00, root mean square error of approximation = .04). Internal consistencies of SNI subscale scores ranged from acceptable to excellent (range α = .67–.92). Most subscales significantly converged with other measures although these associations were minimal for the goal disengagement and reengagement subscales. Limitations The use of an online survey method to collect data introduced sampling bias. Conclusion The eight-factor CFA of the SNI, among Indian adults, was consistent with prior data. Our findings provide preliminary support for the use of SNI to assess the suicidal narrative construct among Indian adults.
Authigenic Formation of Clay Minerals in the Abyssal North Pacific
Authors: Steiner Zvi , Rae James W. B. , Berelson William M. , Adkins Jess F. , Hou Yi , Dong Sijia , Lampronti Giulio I. , Liu Xuewu , Achterberg Eric P. , Subhas Adam V. , Turchyn Alexandra V.
Published: November 2022

Present estimates of the biogeochemical cycles of calcium, strontium, and potassium in the ocean reveal large imbalances between known input and output fluxes. Using pore fluid, incubation, and solid sediment data from North Pacific multi‐corer cores we show that, contrary to the common paradigm, the top centimeters of abyssal sediments can be an active site of authigenic precipitation of clay minerals. In this region, clay authigenesis is the dominant sink for potassium and strontium and consumes nearly all calcium released from benthic dissolution of calcium carbonates. These observations support the idea that clay authigenesis occurring over broad regions of the world ocean may be a major buffer for ocean chemistry on the time scale of the ocean overturning circulation, and key to the long‐term stability of Earth's climate.
Water Balance in Alpine Catchments by Sentinel Data
Authors: Perico R. , Brunner P. , Frattini P. , Crosta G. B.
Published: November 2022

A comprehensive and reliable water balance of snow‐dominated alpine catchments is required for a holistic analysis of the hydrological and hydrogeological processes. A major limitation to the elaboration of this balance in alpine terrain is the difficulty of data acquisition as well as the limited presence of meteorological stations. Remotely sensed data can provide valuable information for the water balance assessment on a regional scale. We exploited Sentinel‐satellite data to estimate the groundwater storage for one hydrologic year in an extensive Alpine catchment located in northern Italy by means of the residual water balance approach. In particular, Evapotranspiration (ET) and Snow Water Equivalent were estimated with the combined use of Sentinel data, at a spatial resolution of 20 and 30 m, respectively. The results show that the adopted satellite‐based methods allow obtaining consistent and physically realistic values to describe the groundwater storage dynamics. In the period 2018–2020, a positive storage occurred only during the snowmelt period and the overall storage was negative, leading to a net lowering of the groundwater level in the floodplain. In addition, the influence of physiographic parameters (altitude, slope, and aspect) and seasonality on the estimates of ET and snow‐depth were investigated.
Effect of Amplitude and Duration of Cyclic Loading on Frictional Sliding Instability in Granular Media: Implication to Earthquake Triggering of Landslides
Authors: Hu Wei , Luo Hui , Xu Qiang , McSaveney Mauri , Huang Runqiu , Zheng Jie , Wang Yujie , Jia Xiaoping
Published: November 2022

Strong earthquakes with larger magnitude and longer durations trigger many landslides, however, how magnitude and duration affect landslides is still unclear. Many factors could contribute to this, including additional shear stress provided by strong ground motion, or “seismogenic liquefaction”; herein, we hypothesize that the dynamic weakening of sliding zone gouge is important. We explored the influence of earthquake magnitude and duration on landslide triggering by simulating the seismic response of sliding zone gouge using a dynamic ring‐shear device and glass spheres. The experiments showed that vibration with larger amplitudes and longer durations more easily trigger deformation and even instability in dry granular materials. We used a dynamic triaxial‐bender system to find that the shear modulus of these materials decreased with the increase in duration and amplitude of cyclic loading. We suggest that this universal decrease in shear modulus is an important landslide‐trigger mechanism. Our results revealed how magnitude and duration of earthquakes affect co‐seismic landslides and why earthquakes with larger magnitude and long durations can trigger more co‐seismic landslides.
Power‐Law Viscoelastic Flow of the Lower Accretionary Prism in the Makran Subduction Zone Following the 2013 Baluchistan Earthquake
Authors: Cheng Guo , Barnhart William D. , Li Shaoyang
Published: November 2022

Subduction zone accretionary prisms are commonly modeled as elastic structures where permanent deformation is accommodated by faulting and folding of otherwise elastic materials, yet accretionary prisms may exhibit other deformation styles over relatively short time scales. In this study, we use 6.5‐year (2014–2021) Sentinel‐1 interferometric synthetic aperture radar (InSAR) time‐series of post‐seismic deformation in the Makran accretionary prism of southeast Pakistan to characterize non‐linear viscoelastic deformation within an active accretionary prism on short timescales (months to years). We constructed a series of 3‐D finite‐element models of the Makran subduction zone, including an accretionary prism, and constrained the elastic thickness of the upper wedge and the flow‐law parameters (power‐law exponent, activation enthalpy, and pre‐exponential constant) of the lower wedge through forward model fits to the InSAR time‐series. Our results show that the prism is elastically thin (8–12 km) and the non‐linear viscoelastic relaxation of the deep portions of the prism alone can sufficiently explain the post‐seismic surface deformation. Our best fitting flow‐law parameters (n = 3.76 ± 0.39, Q = 82.2 ± 37.73 kJ mol−1, and A = 10−3.36±4.69) are consistent with triggering of low temperature dislocation creep within fluid‐saturated siliciclastic rocks. We believe that the fluids necessary for this weakening originate from sedimentary underplating and/or the presence the hydrocarbons. The presence of power‐law rheology within the lower wedge impacts the estimated plate coupling and the stress state in the subduction system, with respect to the conventional elastic wedge model, and hence should to be considered in future earthquake cycle models.
Alpine Fault‐Related Microstructures and Anisotropy of the Mantle Beneath the Southern Alps, New Zealand
Authors: Shao Yilun , Prior David J. , Scott James M. , Kidder Steven B. , Negrini Marianne
Published: November 2022

Mantle xenoliths from the Southern Alps, New Zealand, provide insight into the origin of mantle seismic anisotropy related to the Australian‐Pacific plate boundary. Most xenoliths from within 100 km lateral distance of the Alpine Fault are coarse grained, but a small number are finer grained protomylonites. The protomylonites contain connected networks of fine grains with a different crystallographic preferred orientation (CPO) to coarse porphyroclasts in the same xenolith, suggesting that protomylonites and coarse‐grained samples record different deformation kinematics. The CPOs of fine grains in protomylonites have monoclinic symmetry, with the 2‐fold rotation axis normal to a plane that contains olivine [010] and orthopyroxene [100] maxima, suggesting that the protomylonite deformation involved significant simple shear. Some coarse‐grained samples contain unconnected lenses and layers of fine grains with the same CPO as the coarse grains. Microstructures suggest that these fine grains formed by subgrain rotation recrystallization and that protomylonites may represent an up‐strain progression of this microstructure, where the connectivity of fine grains has allowed them to localize shear and develop a new Alpine Fault CPO. The samples tell us about the state of the mantle at 25 Ma, in the early history of the plate boundary. If this suite of samples is representative of the mantle beneath the Alpine Fault in the present day, then we can interpret the complex seismic anisotropy patterns in the lithospheric mantle as representative of blocks containing variably rotated older CPOs juxtaposed by narrow shear zones associated with Alpine Fault deformation.
Imaging of Small‐Scale Heterogeneity and Absorption Using Adjoint Envelope Tomography: Results From Laboratory Experiments
Authors: Zhang Tuo , Sens‐Schönfelder Christoph , Epple Niklas , Niederleithinger Ernst
Published: November 2022

To complement the information provided by deterministic seismic imaging at length scales above a certain resolution limit we present the first application of adjoint envelope tomography (AET) to experimental data. AET uses the full envelopes of seismic records including scattered coda waves to obtain information about the distribution of absorption and small‐scale heterogeneity which provide complementary information about the investigated medium. Being below the resolution limit this small‐scale structure cannot be resolved by conventional tomography but still affects wave propagation by attenuating ballistic waves and generating scattered waves. Using ultrasound data from embedded sensors in a meter‐sized concrete specimen we image the distribution of absorption and heterogeneity expressed by the intrinsic quality factor Q−1 and the fluctuation strength ɛ that characterizes the strength of the heterogeneity. The forward problem is solved by modeling the 2‐D multiple nonisotropic scattering in an acoustic medium with spatially variable heterogeneity and attenuation using the Monte‐Carlo method. Gradients for the model updates are obtained by convolution with the back‐propagated envelope misfit using the adjoint formalism in analogy to full waveform inversion. We use a late coda time window to invert for absorption and an earlier time window to infer the distribution of heterogeneity. The results successfully locate an area of salt concrete with increased scattering and concentric anomalies of intrinsic attenuation. The resolution test shows that the recovered anomalies constitute reasonable representations of internal structure of the specimen.
Cascading Delays in the Monsoon Rice Growing Season and Postmonsoon Agricultural Fires Likely Exacerbate Air Pollution in North India
Authors: Liu T. , Mickley L. J. , Patel P. N. , Gautam R. , Jain M. , Singh S. , Balwinder‐Singh  , DeFries R. S. , Marlier M. E.
Published: November 2022

Over the past two decades, smoke aerosols from crop residue burning have increasingly degraded postmonsoon (October‐November) air quality in north India. We use satellite data and atmospheric modeling to investigate whether cascading delays in monsoon rice growth and postmonsoon fires over 2003–2019 have exacerbated the already poor urban air quality downwind of the fires. Beginning in 2008, a government effort to combat groundwater depletion in Punjab mandated rice sowing until closer to the arrival of monsoon rains. We find evidence of district‐level delays in the timing of both monsoon rice growth and postmonsoon fires, which vary from 1 to 4 weeks with largely an east‐west gradient. These delays are correlated spatially (r = 0.51–0.77), with northern and western districts in Punjab, which rely less on groundwater for irrigation, tending to have the greatest delays. Had the delays in fire activity not occurred, we estimate that cities downwind and near the fire source would have consistently seen less smoke‐related fine particulate matter (PM2.5), on average ranging from 11% to 21% for New Delhi, Bathinda, and Jind during 2008–2019. This net benefit of earlier postmonsoon burning could have been even larger given that (a) a longer rice‐to‐wheat transition could incentivize farmers to find alternatives to burning crop residues; and (b) background PM2.5 is less abundant earlier in the season, decreasing the likelihood of extreme pollution episodes. Strategies aiming to mitigate air pollution while conserving groundwater may be more effective by promoting an earlier monsoon growing season in districts with less groundwater depletion.
Full‐Tracking Algorithm for Convective Thunderstorm System From Initiation to Complete Dissipation
Authors: Yin Jianhua , Pan Zengxin , Rosenfeld Daniel , Mao Feiyue , Zang Lin , Zhu Yannian , Hu Jiaxi , Chen Jiangping , Gong Jianya
Published: November 2022

Accurate tracking of all components (including core, anvil, and cirrus) of deep convective systems (DCSs) throughout their lifecycle is key to quantifying their impacts on radiative forcing, especially of the anvil and cirrus. Here, a new Full‐tracking Algorithm for Convective Thunderstorm System is developed based on geostationary satellite. It successfully tracks DCSs starting from the initial core to complete dissipation of cirrus detrained from them, and integrates all the related components that split from the initial convective core into a whole DCS. Results show that more than half of the tracked DCSs experience splitting evolutions, with an average of eight sub‐cores during their lifetime. With tracking cirrus generated by DCSs, the lifetime of DCSs is lengthened by up to 10 hr, and their area is enlarged by 16% on average. Generally, long‐lived DCSs have lower cloud top temperature, greater rainfall, and larger area, with more frequent splitting evolutions than short‐lived DCSs. Additionally, DCSs always reach their peaks within 6 hr after initiation regardless of their lifetime. This paper provides a basis for further quantifying the evolution of DCS properties, their impacts on the global radiation budget, and the water cycle in the climate system.
The Origin of the Fracture Networks in the Mudstones of Gale Crater Mars; Their Implications Regarding the State of Stress and Fluid Pressure During Their Formation and the Depth to Which They Were Buried
Authors: Cosgrove John W. , Banham Steven G. , Gupta Sanjeev , Barnes Robert
Published: November 2022

The aim of this article is to establish what can be determined about conditions on Mars during the formation of the fractures and veins that characterize the mudstones which crops out in Gale crater, and to determine whether these rocks represent superficial, alluvial deposits which have remained close to the surface or whether they have been subjected to significant burial and compaction. Spectacular, close‐up images of the fracture and vein networks on horizontal bedding planes reveal their geometries in great detail and this facilitates fracture analysis, a technique that can be used to determine the order in which the various fractures were formed and the stress field operating during their formation. The veins and their textures give an indication of the mechanism of formation of the fractures and of the possible role of high fluid pressures. In addition, the geometry of the veins when viewed in a vertical section can be used to indicate the amount of compaction that the mudstones have experienced which can be used to estimate the minimum depth of burial that has occurred.
Magnetic Evidence for an Extended Hydrogen Exosphere at Mercury
Authors: Schmid D. , Lammer H. , Plaschke F. , Vorburger A. , Erkaev N. V. , Wurz P. , Narita Y. , Volwerk M. , Baumjohann W. , Anderson B. J.
Published: November 2022

Remote observations by the Mariner 10 and MErcury Surface, Space ENvironment, GEophysics, and Ranging (MESSENGER) spacecraft have shown the existence of hydrogen in the exosphere of Mercury. However, to date the hydrogen number densities could only be estimated indirectly from exospheric models, based on the remotely observed Lyman‐α radiances for atomic H, and the detection threshold of the Mariner 10 occultation experiment for molecular H2. Here, we show the first on‐site determined altitude‐density profile of atomic H, derived from in situ magnetic field observations by MESSENGER. The results reveal an extended H exosphere with densities that are ∼1–2 orders of magnitude larger than previously predicted. Using an exospheric model that reproduces the H altitude‐density profile allows us to constrain the so far unknown H2 density at the surface, which is ∼2–3 orders of magnitude smaller than previously assumed. These findings demonstrate the importance of (a) in situ measurements supporting remote observations of Mercury's exosphere that will be realized in the near future by the BepiColombo mission and (b) that dissociation processes play a crucial role in Mercury's exosphere.
Daily Dynamo Electric Fields Derived by Using Equatorial Ionization Anomaly Crests of the Total Electron Content
Authors: Cheng Ching‐Chung , Liu Jann‐Yenq , Lin Charles C. H. , Cheng Yin‐Chen
Published: November 2022

Latitudinal distances between the two equatorial ionization anomaly (EIA) crests in total electron content (TEC) of global ionosphere map (GIM) are used to derive the daily dynamo eastward electric field by comparing the eastward electric field calculated by ROCSAT‐1 vertical ion velocity in four seasons. The electric fields derived by the EIA crests of GIM TEC, ROCSAT‐1 ion velocity, and the incoherent scatter radar (ISR) observations at Jicamarca are generally in good agreement in longitudes and seasons. Meanwhile, the electric fields derived by the EIA crests agree well with those by ROCSAT‐1, FORMOSAT‐7/COSMIC‐2, and Jicamarca ISR on individual days. A long‐term study of the GIM‐TEC crest distance reveals obvious solar activity dependency of the daily dynamo electric field during 1999–2020. These agreements confirm that the EIA crest can be used to derive the daily eastward dynamo electric field and the associated vertical ion velocity which is responsible to the strength of equatorial plasma fountain and the latitudinal extend of the EIA. Moreover, the vertical ion velocity derived by the GIM‐TEC crest distance is further used to improve the SAMI2 model for space weather applications.
ICESat‐2 Based River Surface Slope and Its Impact on Water Level Time Series From Satellite Altimetry
Authors: Scherer Daniel , Schwatke Christian , Dettmering Denise , Seitz Florian
Published: November 2022

The water surface slope (WSS) of rivers is essential for estimating flow velocity and discharge. It is also helpful as a correction applied to range measurements of satellite altimetry missions to derive water level time series at a virtual station. Using radar altimetry, WSS can only be roughly estimated and is limited to wide rivers because of its coarse spatiotemporal resolution. In contrast, the lidar sensor onboard Ice, Cloud, and Land Elevation Satellite 2 (ICESat‐2) can also observe small rivers. Using ICESat‐2's unique measurement geometry with six parallel laser beams, we derive instantaneous WSS along and across the satellite's ground track, time‐variable WSS (with an average of 5 days of records in the studied epoch between October 2018 and October 2021), and average WSS on reach‐scale. Although the method can be applied globally, this study is limited to 815 reaches in Europe and North America where sufficient validation data is available. We compare the ICESat‐2 WSS with time‐variable WSS derived from multiple gauges and constant data from the “SWOT River Database.” For 89% of the studied reaches, ICESat‐2 can be used to estimate the average WSS with a median absolute error of 23 mm/km. We also show the possible performance gain at multiple virtual stations (VS) in the “Database for Hydrological Time Series of Inland Waters” (https://dahiti.dgfi.tum.de), applying the WSS as a correction for altimetry satellites' ground track variability. We correct 137 VS for the derived ICESat‐2 WSS and yield improvements in the root mean square error by up to 30 cm or 66%.
PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer
Authors: Shi Qiyun , Xuhong Juncheng , Luo Tao , Ge Jia , Liu Feng , Lan Yang , Chen Qingqiu , Tang Peng , Fan Linjun , Chen Li , Liang Yan , Wang Minghao , Hu Ying , Zhang Yi , Bian Xiuwu , Qi Xiaowei , Jiang Jun
Published: November 2022

Background

Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer.

Methods

The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored.

Results

Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%;P = 0.00057), and remained significant after a multiple comparison adjustment (Padjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827−0.997) was achieved in the integrated model.

Conclusions

Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.
Bottom-up assembly of viral replication cycles
Authors: Staufer Oskar , Gantner Gösta , Platzman Ilia , Tanner Klaus , Berger Imre , Spatz Joachim P.
Published: November 2022

Bottom-up synthetic biology provides new means to understand living matter by constructing minimal life-like systems. This principle can also be applied to study infectious diseases. Here we summarize approaches and ethical considerations for the bottom-up assembly of viral replication cycles.
speedingCARs: accelerating the engineering of CAR T cells by signaling domain shuffling and single-cell sequencing
Authors: Castellanos-Rueda Rocío , Di Roberto Raphaël B. , Bieberich Florian , Schlatter Fabrice S. , Palianina Darya , Nguyen Oanh T. P. , Kapetanovic Edo , Läubli Heinz , Hierlemann Andreas , Khanna Nina , Reddy Sai T.
Published: November 2022

Chimeric antigen receptors (CARs) consist of an antigen-binding region fused to intracellular signaling domains, enabling customized T cell responses against targets. Despite their major role in T cell activation, effector function and persistence, only a small set of immune signaling domains have been explored. Here we present speedingCARs, an integrated method for engineering CAR T cells via signaling domain shuffling and pooled functional screening. Leveraging the inherent modularity of natural signaling domains, we generate a library of 180 unique CAR variants genomically integrated into primary human T cells by CRISPR-Cas9. In vitro tumor cell co-culture, followed by single-cell RNA sequencing (scRNA-seq) and single-cell CAR sequencing (scCAR-seq), enables high-throughput screening for identifying several variants with tumor killing properties and T cell phenotypes markedly different from standard CARs. Mapping of the CAR scRNA-seq data onto that of tumor infiltrating lymphocytes further helps guide the selection of variants. These results thus help expand the CAR signaling domain combination space, and supports speedingCARs as a tool for the engineering of CARs for potential therapeutic development.
Tempo: an unsupervised Bayesian algorithm for circadian phase inference in single-cell transcriptomics
Authors: Auerbach Benjamin J. , FitzGerald Garret A. , Li Mingyao
Published: November 2022

The circadian clock is a 24 h cellular timekeeping mechanism that regulates human physiology. Answering several fundamental questions in circadian biology will require joint measures of single-cell circadian phases and transcriptomes. However, no widespread experimental approaches exist for this purpose. While computational approaches exist to infer cell phase directly from single-cell RNA-sequencing data, existing methods yield poor circadian phase estimates, and do not quantify estimation uncertainty, which is essential for interpretation of results from very sparse single-cell RNA-sequencing data. To address these unmet needs, we introduce Tempo, a Bayesian variational inference approach that incorporates domain knowledge of the clock and quantifies phase estimation uncertainty. Through simulations and analyses of real data, we demonstrate that Tempo yields more accurate estimates of circadian phase than existing methods and provides well-calibrated uncertainty quantifications. Tempo will facilitate large-scale studies of single-cell circadian transcription.
Deep learning empowered volume delineation of whole-body organs-at-risk for accelerated radiotherapy
Authors: Shi Feng , Hu Weigang , Wu Jiaojiao , Han Miaofei , Wang Jiazhou , Zhang Wei , Zhou Qing , Zhou Jingjie , Wei Ying , Shao Ying , Chen Yanbo , Yu Yue , Cao Xiaohuan , Zhan Yiqiang , Zhou Xiang Sean , Gao Yaozong , Shen Dinggang
Published: November 2022

In radiotherapy for cancer patients, an indispensable process is to delineate organs-at-risk (OARs) and tumors. However, it is the most time-consuming step as manual delineation is always required from radiation oncologists. Herein, we propose a lightweight deep learning framework for radiotherapy treatment planning (RTP), named RTP-Net, to promote an automatic, rapid, and precise initialization of whole-body OARs and tumors. Briefly, the framework implements a cascade coarse-to-fine segmentation, with adaptive module for both small and large organs, and attention mechanisms for organs and boundaries. Our experiments show three merits: 1) Extensively evaluates on 67 delineation tasks on a large-scale dataset of 28,581 cases; 2) Demonstrates comparable or superior accuracy with an average Dice of 0.95; 3) Achieves near real-time delineation in most tasks with <2 s. This framework could be utilized to accelerate the contouring process in the All-in-One radiotherapy scheme, and thus greatly shorten the turnaround time of patients.
Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis
Authors: Hiroto Alex , Kim Won Kyung , Pineda Ariana , He Yongfeng , Lee Dong-Hoon , Le Vien , Olson Adam W. , Aldahl Joseph , Nenninger Christian H. , Buckley Alyssa J. , Xiao Guang-Qian , Geradts Joseph , Sun Zijie
Published: November 2022

The androgen receptor (AR)-signaling pathways are essential for prostate tumorigenesis. Although significant effort has been devoted to directly targeting AR-expressing tumor cells, these therapies failed in most prostate cancer patients. Here, we demonstrate that loss of AR in stromal sonic-hedgehog Gli1-lineage cells diminishes prostate epithelial oncogenesis and tumor development using in vivo assays and mouse models. Single-cell RNA sequencing and other analyses identified a robust increase of insulin-like growth factor (IGF) binding protein 3 expression in AR-deficient stroma through attenuation of AR suppression on Sp1-regulated transcription, which further inhibits IGF1-induced Wnt/β-catenin activation in adjacent basal epithelial cells and represses their oncogenic growth and tumor development. Epithelial organoids from stromal AR-deficient mice can regain IGF1-induced oncogenic growth. Loss of human prostate tumor basal cell signatures reveals in basal cells of stromal AR-deficient mice. These data demonstrate a distinct mechanism for prostate tumorigenesis and implicate co-targeting stromal and epithelial AR-signaling for prostate cancer.
N6-methyladenosine RNA modification promotes viral genomic RNA stability and infection
Authors: Zhang Tianye , Shi Chaonan , Hu Haichao , Zhang Zhuo , Wang Ziqiong , Chen Zhiqing , Feng Huimin , Liu Peng , Guo Jun , Lu Qisen , Zhong Kaili , Chen ZhiHui , Liu Jiaqian , Yu Jiancheng , Chen Jianping , Chen Feng , Yang Jian
Published: November 2022

Molecular manipulation of susceptibility (S) genes that are antipodes to resistance (R) genes has been adopted as an alternative strategy for controlling crop diseases. Here, we show the S gene encoding Triticum aestivum m6A methyltransferase B (TaMTB) is identified by a genome-wide association study and subsequently shown to be a positive regulator for wheat yellow mosaic virus (WYMV) infection. TaMTB is localized in the nucleus, is translocated into the cytoplasmic aggregates by binding to WYMV NIb to upregulate the m6A level of WYMV RNA1 and stabilize the viral RNA, thus promoting viral infection. A natural mutant allele TaMTB-SNP176C is found to confer an enhanced susceptibility to WYMV infection through genetic variation analysis on 243 wheat varieties. Our discovery highlights this allele can be a useful target for the molecular wheat breeding in the future.
Optical gearbox enabled versatile multiscale high-throughput multiphoton functional imaging
Authors: Lin Jianian , Cheng Zongyue , Yang Guang , Cui Meng
Published: November 2022

To understand the function and mechanism of biological systems, it is crucial to observe the cellular dynamics at high spatiotemporal resolutions within live animals. The recent advances in genetically encoded function indicators have significantly improved the response rate to a near millisecond time scale. However, the widely employed in vivo imaging systems often lack the temporal solution to capture the fast biological dynamics. To broadly enable the capability of high-speed in vivo deep-tissue imaging, we developed an optical gearbox. As an add-on module, the optical gearbox can convert the common multiphoton imaging systems for versatile multiscale high-throughput imaging applications. In this work, we demonstrate in vivo 2D and 3D function imaging in mammalian brains at frame rates ranging from 50 to 1000 Hz. The optical gearbox’s versatility and compatibility with the widely employed imaging components will be highly valuable to a variety of deep tissue imaging applications.
Nociceptor neurons affect cancer immunosurveillance
Authors: Balood Mohammad , Ahmadi Maryam , Eichwald Tuany , Ahmadi Ali , Majdoubi Abdelilah , Roversi Karine , Roversi Katiane , Lucido Christopher T. , Restaino Anthony C. , Huang Siyi , Ji Lexiang , Huang Kai-Chih , Semerena Elise , Thomas Sini C. , Trevino Alexandro E. , Merrison Hannah , Parrin Alexandre , Doyle Benjamin , Vermeer Daniel W. , Spanos William C. , Williamson Caitlin S. , Seehus Corey R. , Foster Simmie L. , Dai Hongyue , Shu Chengyi J. , Rangachari Manu , Thibodeau Jacques , V. Del Rincon Sonia , Drapkin Ronny , Rafei Moutih , Ghasemlou Nader , Vermeer Paola D. , Woolf Clifford J. , Talbot Sebastien
Published: November 2022

Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems1–5. Whether the neo-innervation of tumours by pain-initiating sensory neurons affects cancer immunosurveillance remains unclear. Here we show that melanoma cells interact with nociceptor neurons, leading to increases in their neurite outgrowth, responsiveness to noxious ligands and neuropeptide release. Calcitonin gene-related peptide (CGRP)—one such nociceptor-produced neuropeptide—directly increases the exhaustion of cytotoxic CD8+ T cells, which limits their capacity to eliminate melanoma. Genetic ablation of the TRPV1 lineage, local pharmacological silencing of nociceptors and antagonism of the CGRP receptor RAMP1 all reduced the exhaustion of tumour-infiltrating leukocytes and decreased the growth of tumours, nearly tripling the survival rate of mice that were inoculated with B16F10 melanoma cells. Conversely, CD8+ T cell exhaustion was rescued in sensory-neuron-depleted mice that were treated with local recombinant CGRP. As compared with wild-type CD8+ T cells, Ramp1−/− CD8+ T cells were protected against exhaustion when co-transplanted into tumour-bearing Rag1-deficient mice. Single-cell RNA sequencing of biopsies from patients with melanoma revealed that intratumoral RAMP1-expressing CD8+ T cells were more exhausted than their RAMP1-negative counterparts, whereas overexpression of RAMP1 correlated with a poorer clinical prognosis. Overall, our results suggest that reducing the release of CGRP from tumour-innervating nociceptors could be a strategy to improve anti-tumour immunity by eliminating the immunomodulatory effects of CGRP on cytotoxic CD8+ T cells.
Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD
Authors: Gandal Michael J. , Haney Jillian R. , Wamsley Brie , Yap Chloe X. , Parhami Sepideh , Emani Prashant S. , Chang Nathan , Chen George T. , Hoftman Gil D. , de Alba Diego , Ramaswami Gokul , Hartl Christopher L. , Bhattacharya Arjun , Luo Chongyuan , Jin Ting , Wang Daifeng , Kawaguchi Riki , Quintero Diana , Ou Jing , Wu Ye Emily , Parikshak Neelroop N. , Swarup Vivek , Belgard T. Grant , Gerstein Mark , Pasaniuc Bogdan , Geschwind Daniel H.
Published: November 2022

Neuropsychiatric disorders classically lack defining brain pathologies, but recent work has demonstrated dysregulation at the molecular level, characterized by transcriptomic and epigenetic alterations1–3. In autism spectrum disorder (ASD), this molecular pathology involves the upregulation of microglial, astrocyte and neural–immune genes, the downregulation of synaptic genes, and attenuation of gene-expression gradients in cortex1,2,4–6. However, whether these changes are limited to cortical association regions or are more widespread remains unknown. To address this issue, we performed RNA-sequencing analysis of 725 brain samples spanning 11 cortical areas from 112 post-mortem samples from individuals with ASD and neurotypical controls. We find widespread transcriptomic changes across the cortex in ASD, exhibiting an anterior-to-posterior gradient, with the greatest differences in primary visual cortex, coincident with an attenuation of the typical transcriptomic differences between cortical regions. Single-nucleus RNA-sequencing and methylation profiling demonstrate that this robust molecular signature reflects changes in cell-type-specific gene expression, particularly affecting excitatory neurons and glia. Both rare and common ASD-associated genetic variation converge within a downregulated co-expression module involving synaptic signalling, and common variation alone is enriched within a module of upregulated protein chaperone genes. These results highlight widespread molecular changes across the cerebral cortex in ASD, extending beyond association cortex to broadly involve primary sensory regions.
Entorhinal cortex directs learning-related changes in CA1 representations
Authors: Grienberger Christine , Magee Jeffrey C.
Published: November 2022

Learning-related changes in brain activity are thought to underlie adaptive behaviours1,2. For instance, the learning of a reward site by rodents requires the development of an over-representation of that location in the hippocampus3–6. How this learning-related change occurs remains unknown. Here we recorded hippocampal CA1 population activity as mice learned a reward location on a linear treadmill. Physiological and pharmacological evidence suggests that the adaptive over-representation required behavioural timescale synaptic plasticity (BTSP)7. BTSP is known to be driven by dendritic voltage signals that we proposed were initiated by input from entorhinal cortex layer 3 (EC3). Accordingly, the CA1 over-representation was largely removed by optogenetic inhibition of EC3 activity. Recordings from EC3 neurons revealed an activity pattern that could provide an instructive signal directing BTSP to generate the over-representation. Consistent with this function, our observations show that exposure to a second environment possessing a prominent reward-predictive cue resulted in both EC3 activity and CA1 place field density that were more elevated at the cue than at the reward. These data indicate that learning-related changes in the hippocampus are produced by synaptic plasticity directed by an instructive signal from the EC3 that seems to be specifically adapted to the behaviourally relevant features of the environment.
Hydroclimatic vulnerability of peat carbon in the central Congo Basin
Authors: Garcin Yannick , Schefuß Enno , Dargie Greta C. , Hawthorne Donna , Lawson Ian T. , Sebag David , Biddulph George E. , Crezee Bart , Bocko Yannick E. , Ifo Suspense A. , Mampouya Wenina Y. Emmanuel , Mbemba Mackline , Ewango Corneille E. N. , Emba Ovide , Bola Pierre , Kanyama Tabu Joseph , Tyrrell Genevieve , Young Dylan M. , Gassier Ghislain , Girkin Nicholas T. , Vane Christopher H. , Adatte Thierry , Baird Andy J. , Boom Arnoud , Gulliver Pauline , Morris Paul J. , Page Susan E. , Sjögersten Sofie , Lewis Simon L.
Published: November 2022

The forested swamps of the central Congo Basin store approximately 30 billion metric tonnes of carbon in peat1,2. Little is known about the vulnerability of these carbon stocks. Here we investigate this vulnerability using peat cores from a large interfluvial basin in the Republic of the Congo and palaeoenvironmental methods. We find that peat accumulation began at least at 17,500 calibrated years before present (cal. yr bp; taken asad1950). Our data show that the peat that accumulated between around 7,500 to around 2,000 cal. yr bpis much more decomposed compared with older and younger peat. Hydrogen isotopes of plant waxes indicate a drying trend, starting at approximately 5,000 cal. yrbpand culminating at approximately 2,000 cal. yr bp, coeval with a decline in dominant swamp forest taxa. The data imply that the drying climate probably resulted in a regional drop in the water table, which triggered peat decomposition, including the loss of peat carbon accumulated prior to the onset of the drier conditions. After approximately 2,000 cal. yr bp, our data show that the drying trend ceased, hydrologic conditions stabilized and peat accumulation resumed. This reversible accumulation–loss–accumulation pattern is consistent with other peat cores across the region, indicating that the carbon stocks of the central Congo peatlands may lie close to a climatically driven drought threshold. Further research should quantify the combination of peatland threshold behaviour and droughts driven by anthropogenic carbon emissions that may trigger this positive carbon cycle feedback in the Earth system.
Extracellular fluid viscosity enhances cell migration and cancer dissemination
Authors: Bera Kaustav , Kiepas Alexander , Godet Inês , Li Yizeng , Mehta Pranav , Ifemembi Brent , Paul Colin D. , Sen Anindya , Serra Selma A. , Stoletov Konstantin , Tao Jiaxiang , Shatkin Gabriel , Lee Se Jong , Zhang Yuqi , Boen Adrianna , Mistriotis Panagiotis , Gilkes Daniele M. , Lewis John D. , Fan Chen-Ming , Feinberg Andrew P. , Valverde Miguel A. , Sun Sean X. , Konstantopoulos Konstantinos
Published: November 2022

Cells respond to physical stimuli, such as stiffness1, fluid shear stress2and hydraulic pressure3,4. Extracellular fluid viscosity is a key physical cue that varies under physiological and pathological conditions, such as cancer5. However, its influence on cancer biology and the mechanism by which cells sense and respond to changes in viscosity are unknown. Here we demonstrate that elevated viscosity counterintuitively increases the motility of various cell types on two-dimensional surfaces and in confinement, and increases cell dissemination from three-dimensional tumour spheroids. Increased mechanical loading imposed by elevated viscosity induces an actin-related protein 2/3 (ARP2/3)-complex-dependent dense actin network, which enhances Na+/H+exchanger 1 (NHE1) polarization through its actin-binding partner ezrin. NHE1 promotes cell swelling and increased membrane tension, which, in turn, activates transient receptor potential cation vanilloid 4 (TRPV4) and mediates calcium influx, leading to increased RHOA-dependent cell contractility. The coordinated action of actin remodelling/dynamics, NHE1-mediated swelling and RHOA-based contractility facilitates enhanced motility at elevated viscosities. Breast cancer cells pre-exposed to elevated viscosity acquire TRPV4-dependent mechanical memory through transcriptional control of the Hippo pathway, leading to increased migration in zebrafish, extravasation in chick embryos and lung colonization in mice. Cumulatively, extracellular viscosity is a physical cue that regulates both short- and long-term cellular processes with pathophysiological relevance to cancer biology.
Bioinformatics analysis of prognostic value and immunological role of MeCP2 in pan-cancer
Authors: Wang Yanfeng , Zhang Yunqing , Wang Fenghui , Li Ting , Song Xinqiu , Shi Haiyan , Du Juan , Zhang Huahua , Jing Hongmei , Han Jiaqi , Tong Dongdong , Zhang Jing
Published: November 2022

Methyl-CpG-binding protein 2(MeCP2) is an important epigenetic regulatory factor that promotes many tumor developments, such as liver cancer, breast cancer, and colorectal cancer. So far, no pan-cancer analysis has been reported. Therefore, this study aims to explore pan-cancer's prognostic value, immune infiltration pattern, and biological function. We used bioinformatics methods to analyze the expression and prognostic significance of MeCP2, and the relationship between MeCP2 and clinicopathological parameters, genetic variation, methylation, phosphorylation, immune cell infiltration, and biological function in pan-cancer from using a public database. The results showed that expression of MeCP2 was up-regulated in 8 cancers and down-regulated in 2 cancers, which was remarkably correlated with the prognosis, pathological stage, grade and subtype of cancers. The promoter methylation level of MeCP2 DNA was decreased in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), liver hepatocellular carcinoma (LIHC), prostate adenocarcinoma (PRAD), uterine corpus endometrial carcinoma (UCEC), testicular germ cell tumors (TGCT), and stomach adenocarcinoma (STAD);decreased phosphorylation of S25, S90, S92, S241, S286, S325 and S435 was found in MeCP2, such as UCEC, lung adenocarcinoma (LUAD), ovarian serous cystadenocarcinoma (OV), colon adenocarcinoma (COAD), and kidney renal clear cell carcinoma (KIRC). Furthermore, MeCP2 expression was significantly associated with multiple immunomodulators and immune cell infiltration levels across most tumors. Therefore, our pan-cancer explored the prognostic markers and immunotherapeutic value of MeCP2 in different cancers.