bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of sensing system for experimental modeling of soft actuator applied for finger rehabilitation
Authors: Davarzani Shokoufeh , Ahmadi-Pajouh Mohammad Ali , Ghafarirad Hamed
Published: October 2021

Safe interaction and inherent compliance with soft robots have motivated the evolution of soft rehabilitation robots. Among these, soft robotic gloves are known as an effective tool for stroke rehabilitation. This research proposed a pneumatically actuated soft robotic for index finger rehabilitation. The proposed system consists of a soft bending actuator and a sensing system equipped with four inertial measurement unit sensors to generate kinematic data of the index finger. The designed sensing system can estimate the range of motion (ROM) of the finger’s joints by combining angular velocity and acceleration values with the standard Kalman filter. The sensing system is evaluated regarding repeatability and reliability through static and dynamic experiments in the first step. The root mean square error attained in static and dynamic states are 2$^\circ$and 3$^\circ$, sequentially, representing an efficient function of the fusion algorithm. In the next step, experimental models have been developed to analyze and predict a soft actuator’s behavior in free and constrained states using the sensing system’s data. Thus, parametric system identification methods, artificial neural network—multilayer perceptron (ANN-MLP), and artificial neural network—radial basis function algorithms (ANN-RBF) have been compared to achieve an optimal model. The results reveal that ANN models, particularly RBF ones, can predict the actuator behavior with reasonable accuracy in the free and constrained state (<1$^\circ$). Hence, the need for intricate analytical modeling and material characterization will be eliminated, and controlling the soft actuator will be more practical. Besides, it assesses the ROM and finger functionality.
Calcium carbonate saturation states along the West Antarctic Peninsula
Authors: Jones Elizabeth M. , Hoppema Mario , Bakker Karel , de Baar Hein J.W.
Published: October 2021

The waters along the West Antarctic Peninsula (WAP) have experienced warming and increased freshwater inputs from melting sea ice and glaciers in recent decades. Challenges exist in understanding the consequences of these changes on the inorganic carbon system in this ecologically important and highly productive ecosystem. Distributions of dissolved inorganic carbon (CT), total alkalinity (AT) and nutrients revealed key physical, biological and biogeochemical controls of the calcium carbonate saturation state (Ωaragonite) in different water masses across the WAP shelf during the summer. Biological production in spring and summer dominated changes in surface water Ωaragonite (ΔΩaragonite up to +1.39; ~90%) relative to underlying Winter Water. Sea-ice and glacial meltwater constituted a minor source of AT that increased surface water Ωaragonite (ΔΩaragonite up to +0.07; ~13%). Remineralization of organic matter and an influx of carbon-rich brines led to cross-shelf decreases in Ωaragonite in Winter Water and Circumpolar Deep Water. A strong biological carbon pump over the shelf created Ωaragonite oversaturation in surface waters and suppression of Ωaragonite in subsurface waters. Undersaturation of aragonite occurred at < ~1000 m. Ongoing changes along the WAP will impact the biologically driven and meltwater-driven processes that influence the vulnerability of shelf waters to calcium carbonate undersaturation in the future.
Quadricuspid aortic valve and a large patent ductus arteriosus treated with device closure
Authors: Sultan Mehboob , Awan Khush Bakht , Khan Asad
Published: October 2021

Quadricuspid aortic valve is a remarkably rare congenital cardiac anomaly that predominantly becomes regurgitant with the passage of time. Aortic valve stenosis and aortic root dilatation are less common in quadricuspid aortic valve as compared to bicuspid aortic valve. The clinical presentation depends upon the functional status of the aortic valve, left ventricular function, and associated cardiac or coronary anomalies. The quadricuspid aortic valve is easily visualised during transthoracic echocardiogram with a characteristic X pattern of aortic valve in diastole. The association of quadricuspid aortic valve with patent ductus arteriosus is exceedingly rare. We are reporting a case of young girl with mildly regurgitant quadricuspid aortic valve, large patent ductus arteriosus, and volume-loaded left heart who underwent a successful device closure of her patent ductus arteriosus. To the best of our knowledge, such a case is being reported from Pakistan for the first time.
Are interventions delivered by healthcare professionals effective for weight management? A systematic review of systematic reviews
Authors: Epton Tracy , Keyworth Christopher , Goldthorpe Joanna , Calam Rachel , Armitage Christopher J
Published: October 2021

Objective:

There are many systematic reviews of weight management interventions delivered by healthcare professionals (HCP), but it is not clear under what circumstances interventions are effective due to differences in review methodology. This review of systematic reviews synthesises the evidence about: (a) the effectiveness of HCP-delivered weight management interventions and (b) intervention and sample characteristics related to their effectiveness.

Design:

The review of reviews involved searching six databases (inception – October 2020). Reviews were included if they were (a) systematic, (b) weight management interventions delivered, at least partially, by HCP, (c) of randomised controlled trials and (d) written in English. Data regarding weight management outcomes (e.g. weight) and moderating factors were extracted. Secondary analyses were conducted using study-level data reported in each of the reviews.

Setting:

The review included studies that were delivered by HCP in any clinical or non-clinical setting.

Participants:

Not applicable.

Results:

Six systematic reviews were included (forty-six unique studies). First-level synthesis showed that weight management interventions delivered by HCP are effective. The second-level synthesis found that interventions are only successful for up to 6 months, are most effective for women, non-Caucasians and adults and are most effective if they have at least six sessions.

Conclusions:

As interventions are only successful for up to 6 months, they are not sufficient for achieving and maintaining a healthy weight.
Developmental Origins of Health and Disease, resilience and social justice in the COVID era
Authors: Penkler Michael , Jacob Chandni M , Müller Ruth , Kenney Martha , Norris Shane A. , da Costa Clarissa P , Richardson Sarah S. , Roseboom Tessa J. , Hanson Mark
Published: October 2021

The COVID-19 pandemic has shone a spotlight on how health outcomes are unequally distributed among different population groups, with disadvantaged communities and individuals being disproportionality affected in terms of infection, morbidity and mortality, as well as vaccine access. Recently, there has been considerable debate about how social disadvantage and inequality intersect with developmental processes to result in a heightened susceptibility to environmental stressors, economic shocks and large-scale health emergencies. We argue that DOHaD Society members can make important contributions to addressing issues of inequality and improving community resilience in response to COVID-19. In order to do so, it is beneficial to engage with and adopt a social justice framework. We detail how DOHaD can align its research and policy recommendations with a social justice perspective to ensure that we contribute to improving the health of present and future generations in an equitable and socially just way.
Rapid necrosis II: physiological and molecular analysis of 2,4-D resistance in Sumatran fleabane (Conyza sumatrensis)
Authors: de Queiroz Andrew R. S. , Delatorre Carla A. , Markus Catarine , Lucio Felipe R. , Angonese Paula S. , Merotto Aldo
Published: October 2021

In 2015, plants of Sumatran fleabane [Conyza sumatrensis (Retz.) E. Walker] were identified in a crop field with an unusual rapid necrosis herbicide symptom after application of 2,4-D. An initial study identified that the symptoms began about 2 h after herbicide application, the resistance factor was high (resistance factor = 19), and the resistance decreased at low light. The mechanism of resistance is not yet known, but the symptomatology suggests it may be related to reduced translocation, ATP-binding cassette (ABC) class B transporters, changes on auxin perception genes, or induction of genes involved in response to pathogens and abiotic stresses. The objective of this study was to use inhibitors of enzymes involved in detoxification and carriers to investigate the mechanisms involved in the resistance to 2,4-D caused by rapid necrosis. Neither the inhibitors of ABC and auxin transporters, triiodobenzoic acid (TIBA), 1-N-naphythylphthalamic acid (NPA), verapamil, and orthovanadate, nor the inhibitors of detoxifying enzymes, such as malathion, 4-chloro-7-nitrobenzofurazan (NBD-Cl), and imidazole, reduced the frequency of the rapid necrosis phenotype. However, orthovanadate and sodium azide (possibly related to auxin transport) were able to partially reduce oxidative stress in leaf disks. The expression of ABCM10 (an ABCD transporter gene), TIR1_1 (an auxin receptor gene), and CAT4 (an amino acid transporter gene) was quickly reduced after 2,4-D application in the resistant accession. Contrary to our hypothesis, LESION SIMULATING DISEASE RESISTANCE 1_3 (LSD1_3) expression increased in response to 2,4-D. LSD1_3 is important for the response to pathogen and abiotic stresses. The rapid necrosis mechanism is not related to 2,4-D detoxification but might be related to changes in the TIR receptor or auxin transport. Mutations in other transporters or in proteins involved in abiotic and pathogen stresses cannot be ruled out.
Properties of Saharan Dust Versus Local Urban Dust—A Case Study
Authors: Szczepanik Dominika M. , Stachlewska Iwona S. , Tetoni Eleni , Althausen Dietrich
Published: October 2021

On June 29–30, 2019, the Barcelona Dust Forecast Center with Non‐hydrostatic Multiscale Model (NMMB/BSC‐Dust) and the Navy Aerosol Analysis and Prediction System forecasted huge amounts of mineral dust over Poland. The Hybrid Single Particle Lagrangian Integrated Trajectory model confirmed uniquely fast (120 hr) long‐range air‐mass transport form North Africa to Poland. This remarkable dust event was observed using lidar at the Aerosol, Clouds and Trace Gases Research InfraStructure site in Warsaw, Central Poland; the only site equipped with Raman‐Mie polarization water vapor lidar in East‐Central Europe. The excellent capabilities of PollyXT lidar allowed to obtain an impressive number of 31 full sets of aerosol optical properties profiles, which enabled study of dust properties evolution on a rare hourly scale. The analyses were completed with the separation of fine and coarse mode dust particles form non‐dust particles using the POlarization‐LIdar PHOtometer Networking algorithm. Huge amount of an exceptionally pure mineral dust from Sahara measured in the free troposphere was characterized by a gradually decreasing coarse dust fraction (76%–21%) with a peak of fine dust fraction (67%) and particle linear depolarization ratio (26%) in the middle of the event. Within the boundary layer, a local urban dust mixed with pollution was observed with fine mode dust particles dominating (44%) and lower particle linear depolarization ratio (7.4%). The influx of pure mineral dust has been unique to this geographical region and will therefore be a reference point for future research and comparative studies.
Future Summer Marine Heatwaves in the Western South Atlantic
Authors: Costa Natasha V. , Rodrigues Regina R.
Published: October 2021

Marine heatwaves (MHWs) are periods of abnormally high ocean temperatures and their impacts threaten physical, biological, and human systems. Here, we show through different scenarios of the Coupled Model Intercomparison Project Phase 6 (CMIP6) that significant positive trends in frequency, duration, and cumulative intensity are identified for the western South Atlantic, leading to an almost permanent state of MHW by the end of the 21st century considering a constant baseline. We also find that the main mechanism that causes MHWs in this region, atmospheric blocking, is likely to intensify in the future. Thus, the increase in occurrence of MHWs is not just due to the direct effect of long‐term warming. Moreover, the largest trends occur during 2021–2050, and not during 2071–2100. This has important implications for marine ecosystems and the ocean ability of absorbing heat and CO2, underlying the urgency for a global reduction in greenhouse gas emissions.
Varying Partitioning of Surface Turbulent Fluxes Regulates Temperature‐Humidity Dissimilarity in the Convective Atmospheric Boundary Layer
Authors: Liu Cheng , Liu Heping , Huang Jianping , Xiao Hongwei
Published: October 2021

Experimental evidence shows that temperature‐humidity () similarity in the atmospheric surface layer (ASL) is reduced as Bowen ratio () increases over land. However, underlying physical mechanisms remain not well understood. With large‐eddy simulations, dissimilarity is investigated in the steady‐state, convective boundary layer (CBL) over homogeneous landscape with varying . As increases from 0.4 to 2.0, the entrainment ratio for slightly decreases but that for q largely increases. As a result, local production of humidity variance is substantially enhanced in the upper CBL and transported to the lower CBL by vigorous large eddies, contributing significantly to nonlocal fraction. However, the increased temperature variance in the ASL associated with strong heat flux is larger than that transported from the upper CBL. Such asymmetry in vertical diffusion induced by varying partitioning of surface fluxes strongly regulates dissimilarity even under perfect conditions valid for Monin‐Obukhov similarity theory.
Deep Learning Estimation of Daily Ground‐Level NO2 Concentrations From Remote Sensing Data
Authors: Ghahremanloo Masoud , Lops Yannic , Choi Yunsoo , Yeganeh Bijan
Published: October 2021

The limited number of nitrogen dioxide (NO2) surface measurements calls for the development of highly accurate approaches to estimating surface NO2 concentrations. In this study, we leverage a new satellite instrument, the TROPOspheric Monitoring Instrument (TROPOMI), along with other predictor variables, to estimate daily surface NO2 concentrations over Texas in 2019. We use the deep convolutional neural network (Deep‐CNN), an advanced deep learning algorithm, to obtain estimates and achieve a correlation coefficient (R) of 0.91, an index of agreement (IOA) of 0.95, and a mean absolute bias (MAB) of 1.75 ppb in surface NO2 estimation. Additionally, we leverage a novel approach, shapley additive explanations (SHAP), to describe how Deep‐CNN understands each predictor variable. The SHAP results show that the Deep‐CNN model has an advanced understanding of the data set, revealing that TROPOMI closely captures levels of NO2. In addition, we show the superiority of our Deep‐CNN model at estimating surface NO2 over other well‐known machine learning and regression models in the field, including the support vector machines (SVM), random forest (RF), and multiple linear regression (MLR). Although SVM and RF show strong capabilities at estimating surface NO2 concentrations, their accuracy is inferior to that of the Deep‐CNN model, ranking second and third in model accuracy in this study. The MLR, however, shows a poor ability at NO2 estimation and ranks last among all models. Testing the impact of sample size on model performance, we also show that, compared to other models, Deep‐CNN needs more samples to trigger its strength at surface NO2 estimation.
Impact of Unmitigated HFC Emissions on Stratospheric Ozone at the End of the 21st Century as Simulated by Chemistry‐Climate Models
Authors: Dupuy Eric , Akiyoshi Hideharu , Yamashita Yousuke
Published: October 2021

Hydrofluorocarbons (HFCs) have been increasingly replacing chlorofluorocarbons and hydrochlorofluorocarbons. Although their direct chemical ozone‐depleting potential is negligible, as potent greenhouse gases they modify atmospheric temperature and circulation patterns, thereby indirectly influencing stratospheric ozone recovery. Measurements and model projections must continue to evaluate HFC limitation measures and assess the long‐term impact of HFCs on the atmospheric radiation budget and stratospheric ozone. In this study, we present multi‐member ensemble simulations designed to estimate the impact of HFCs on stratospheric temperature, ozone and circulation changes at the end of the century. We compared simulations with and without HFCs for two three‐dimensional chemistry‐climate models that use the same chemistry module but different physical schemes. At low and mid‐latitudes, temperature and ozone responses were comparable for both models and in general agreement with previous studies. HFCs induced a marked temperature increase up to about 10–20 hPa and vertically alternating positive and negative ozone anomalies. We explained this pattern by competing effects of vertical motion (low and middle stratosphere) and temperature (upper stratosphere) anomalies. At northern high latitudes, there were strong discrepancies with previous studies and between the models themselves, attributed to differences in ozone anomalies caused by wave activity during winter. Quantitatively, we found a net positive, but small, HFC impact on total ozone amounts. Largest anomalies were less than 1% in the winter polar stratosphere. Our results indicate that increasing HFC amounts will likely have a limited impact on stratospheric ozone recovery within this century, with large uncertainty in the polar regions.
Effects of Hydrogen on the Phase Relations in Fe‐FeS at Pressures of Mars‐Sized Bodies
Authors: Piet H. , Leinenweber K. , Greenberg E. , Prakapenka V. B. , Shim S.‐H.
Published: October 2021

The large radius, and therefore low density, of the Martian core found in the InSight mission data analysis highlights the importance of considering other light elements besides sulfur (S), which has been considered as the main light element for Mars for decades. Hydrogen (H) is abundant in the solar system and becomes siderophile at high pressures. Although Fe‐S and Fe‐H systems have been studied individually, the Fe‐S‐H ternary system has only been investigated up to 16 GPa and 1723 K. We have investigated the Fe‐S‐H system at pressures and temperatures (P‐T) relevant to the cores of Mars‐sized planets (up to 45 GPa and well above the melting temperature of FeS) in the laser‐heated diamond anvil cell combined with in situ synchrotron X‐ray diffraction. We found that sufficient hydrogen leads to the disappearance of Fe3S at high P‐T. Instead, separate Fe‐H and Fe‐S phases appear at 23–35 GPa. At pressures above 35 GPa, we found a new phase appearing while Fe‐S phases disappear and Fe‐H phases remain. Our analysis indicates that the new phase likely contains both S and H in the crystal structure (tentatively FeSxHy where x ≈ 1 and y ≈ 1). The observed pressure‐dependent changes in the phase relation may be important for understanding the structure and dynamics of the Martian core and the cores of Mars‐sized exoplanets.
Inhibition of the RacGEF VAV3 by the small molecule IODVA1 impedes RAC signaling and overcomes resistance to tyrosine kinase inhibition in acute lymphoblastic leukemia
Authors: Hegde Shailaja , Gasilina Anjelika , Wunderlich Mark , Lin Yuan , Buchholzer Marcel , Krumbach Oliver H. F. , Akbarzadeh Mohammad , Ahmadian Mohammad Reza , Seibel William , Zheng Yi , Perentesis John P. , Mizukawa Benjamin E. , Vinnedge Lisa Privette , Cancelas José A. , Nassar Nicolas N.
Published: October 2021

Aberrant RHO guanine nucleotide exchange factor (RhoGEF) activation is chief mechanism driving abnormal activation of their GTPase targets in transformation and tumorigenesis. Consequently, a small-molecule inhibitor of RhoGEF can make an anti-cancer drug. We used cellular, mouse, and humanized models of RAC-dependent BCR-ABL1-driven and Ph-like acute lymphoblastic leukemia to identify VAV3, a tyrosine phosphorylation–dependent RacGEF, as the target of the small molecule IODVA1. We show that through binding to VAV3, IODVA1 inhibits RAC activation and signaling and increases pro-apoptotic activity in BCR-ABL1-transformed cells. Consistent with this mechanism of action, cellular and animal models of BCR-ABL1-induced leukemia in Vav3-null background do not respond to IODVA1. By durably decreasing in vivo RAC signaling, IODVA1 eradicates leukemic propagating activity of TKI-resistant BCR-ABL1(T315I) B-ALL cells after treatment withdrawal. Importantly, IODVA1 suppresses the leukemic burden in the treatment refractory pediatric Ph+ and TKI-resistant Ph+ B-ALL patient-derived xenograft models better than standard-of-care dasatinib or ponatinib and provides a more durable response after treatment withdrawal. Pediatric leukemia samples with diverse genetic lesions show high sensitivity to IODVA1 ex vivo and this sensitivity is VAV3 dependent. IODVA1 thus spearheads a novel class of drugs that inhibits a RacGEF and holds promise as an anti-tumor therapy.
Shrinking multiplexed orbital angular momentum to the nanoscale
Authors: He Chao , Shen Yijie , Forbes Andrew , Booth Martin J.
Published: October 2021

Orbital angular momentum interactions at the nanoscale have remained elusive because the phase structure becomes unresolved. Now researchers have shown how to overcome this with tightly focused beams, demonstrating a record-high six-dimensional encoding in an ultra-dense nanoscale volume.
Networks of worry—towards a connectivity-based signature of late-life worry using higher criticism
Authors: Gerlach Andrew R. , Karim Helmet T. , Kazan Joseph , Aizenstein Howard J. , Krafty Robert T. , Andreescu Carmen
Published: October 2021

Severe worry is a complex transdiagnostic phenotype independently associated with increased morbidity, including cognitive impairment and cardiovascular diseases. We investigated the neurobiological basis of worry in older adults by analyzing resting state fMRI using a large-scale network-based approach. We collected resting fMRI on 77 participants (>50 years old) with varying worry severity. We computed region-wise connectivity across the default mode network (DMN), anterior salience network, and left executive control network. All 22,366 correlations were regressed on worry severity and adjusted for age, sex, race, education, disease burden, depression, anxiety, rumination, and neuroticism. We employed higher criticism, a second-level method of significance testing for rare and weak features, to reveal the functional connectivity patterns associated with worry. The analysis suggests that worry has a complex, yet distinct signature associated with resting state functional connectivity. Intra-connectivities and inter-connectivities of the DMN comprise the dominant contribution. The anterior cingulate, temporal lobe, and thalamus are heavily represented with overwhelmingly negative association with worry. The prefrontal regions are also strongly represented with a mix of positive and negative associations with worry. Identifying the most salient connections may be useful for targeted interventions for reducing morbidity associated with severe worry in older adults.
Diversity of cell death signaling pathways in macrophages upon infection with modified vaccinia virus Ankara (MVA)
Authors: Klaas Lioba , Vier Juliane , Gentle Ian E. , Häcker Georg , Kirschnek Susanne
Published: October 2021

Regulated cell death frequently occurs upon infection by intracellular pathogens, and extent and regulation is often cell-type-specific. We aimed to identify the cell death-signaling pathways triggered in macrophages by infection with modified vaccinia virus Ankara (MVA), an attenuated strain of vaccinia virus used in vaccination. While most target cells seem to be protected by antiapoptotic proteins encoded in the MVA genome, macrophages die when infected with MVA. We targeted key signaling components of specific cell death-pathways and pattern recognition-pathways using genome editing and small molecule inhibitors in an in vitro murine macrophage differentiation model. Upon infection with MVA, we observed activation of mitochondrial and death-receptor-induced apoptosis-pathways as well as the necroptosis-pathway. Inhibition of individual pathways had a little protective effect but led to compensatory death through the other pathways. In the absence of mitochondrial apoptosis, autocrine/paracrine TNF-mediated apoptosis and, in the absence of caspase-activity, necroptosis occurred. TNF-induction depended on the signaling molecule STING, and MAVS and ZBP1 contributed to MVA-induced apoptosis. The mode of cell death had a substantial impact on the cytokine response of infected cells, indicating that the immunogenicity of a virus may depend not only on its PAMPs but also on its ability to modulate individual modalities of cell death. These findings provide insights into the diversity of cell death-pathways that an infection can trigger in professional immune cells and advance our understanding of the intracellular mechanisms that govern the immune response to a virus.
Akt-mediated Ephexin1–Ras interaction promotes oncogenic Ras signaling and colorectal and lung cancer cell proliferation
Authors: Kim Jeeho , Jeon Young Jin , Lim Sung-Chul , Ryu Joohyun , Lee Jung-Hee , Chang In-Youb , You Ho Jin
Published: October 2021

Abstrct

Ephexin1 was reported to be highly upregulated by oncogenic Ras, but the functional consequences of this remain poorly understood. Here, we show that Ephexin1 is highly expressed in colorectal cancer (CRC) and lung cancer (LC) patient tissues. Knockdown of Ephexin1 markedly inhibited the cell growth of CRC and LC cells with oncogenic Ras mutations. Ephexin1 contributes to the positive regulation of Ras-mediated downstream target genes and promotes Ras-induced skin tumorigenesis. Mechanically, Akt phosphorylates Ephexin1 at Ser16 and Ser18 (pSer16/18) and pSer16/18 Ephexin1 then interacts with oncogenic K-Ras to promote downstream MAPK signaling, facilitating tumorigenesis. Furthermore, pSer16/18 Ephexin1 is associated with both an increased tumor grade and metastatic cases of CRC and LC, and those that highly express pSer16/18 exhibit poor overall survival rates. These data indicate that Ephexin1 plays a critical role in the Ras-mediated CRC and LC and pSer16/18 Ephexin1 might be an effective therapeutic target for CRC and LC.
RETRACTED ARTICLE: Inhibition of TGF-β repairs spinal cord injury by attenuating EphrinB2 expressing through inducing miR-484 from fibroblast
Authors: Pan Dayu , Yang Fuhan , Zhu Shibo , Li Yongjin , Ning Guangzhi , Feng Shiqing
Published: October 2021

Spinal cord injury (SCI) can lead to severe loss of motor and sensory function with high disability and mortality. The effective treatment of SCI remains unknown. Here we find systemic injection of TGF-β neutralizing antibody induces the protection of axon growth, survival of neurons, and functional recovery, whereas erythropoietin-producing hepatoma interactor B2 (EphrinB2) expression and fibroblasts distribution are attenuated. Knockout of TGF-β type II receptor in fibroblasts can also decrease EphrinB2 expression and improve spinal cord injury recovery. Moreover, miR-488 was confirmed to be the most upregulated gene related to EphrinB2 releasing in fibroblasts after SCI and miR-488 initiates EphrinB2 expression and physical barrier building through MAPK signaling after SCI. Our study points toward elevated levels of active TGF-β as inducer and promoters of fibroblasts distribution, fibrotic scar formation, and EphrinB2 expression, and deletion of global TGF-β or the receptor of TGF-β in Col1α2 lineage fibroblasts significantly improve functional recovery after SCI, which suggest that TGF-β might be a therapeutic target in SCI.
A cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries
Authors: Sera Francesco , Armstrong Ben , Abbott Sam , Meakin Sophie , O’Reilly Kathleen , von Borries Rosa , Schneider Rochelle , Royé Dominic , Hashizume Masahiro , Pascal Mathilde , Tobias Aurelio , Vicedo-Cabrera Ana Maria ,   MCC Collaborative Research Network, Hu Wenbiao , Tong Shilu , Lavigne Eric , Correa Patricia Matus , Meng Xia , Kan Haidong , Kynčl Jan , Urban Aleš , Orru Hans , Ryti Niilo R. I. , Jaakkola Jouni J. K. , Cauchemez Simon , Dallavalle Marco , Schneider Alexandra , Zeka Ariana , Honda Yasushi , Ng Chris Fook Sheng , Alahmad Barrak , Rao Shilpa , Di Ruscio Francesco , Carrasco-Escobar Gabriel , Seposo Xerxes , Holobâcă Iulian Horia , Kim Ho , Lee Whanhee , Íñiguez Carmen , Ragettli Martina S. , Aleman Alicia , Colistro Valentina , Bell Michelle L. , Zanobetti Antonella , Schwartz Joel , Dang Tran Ngoc , Scovronick Noah , de Sousa Zanotti Stagliorio Coélho Micheline , Diaz Magali Hurtado , Zhang Yuzhou ,   CMMID COVID-19 Working Group, Russell Timothy W. , Koltai Mihaly , Kucharski Adam J. , Barnard Rosanna C. , Quaife Matthew , Jarvis Christopher I. , Lei Jiayao , Munday James D. , Chan Yung-Wai Desmond , Quilty Billy J. , Eggo Rosalind M. , Flasche Stefan , Foss Anna M. , Clifford Samuel , Tully Damien C. , Edmunds W. John , Klepac Petra , Brady Oliver , Krauer Fabienne , Procter Simon R. , Jombart Thibaut , Rosello Alicia , Showering Alicia , Funk Sebastian , Hellewell Joel , Sun Fiona Yueqian , Endo Akira , Williams Jack , Gimma Amy , Waterlow Naomi R. , Prem Kiesha , Bosse Nikos I. , Gibbs Hamish P. , Atkins Katherine E. , Pearson Carl A. B. , Jafari Yalda , Villabona-Arenas C. Julian , Jit Mark , Nightingale Emily S. , Davies Nicholas G. , van Zandvoort Kevin , Liu Yang , Sandmann Frank G. , Waites William , Abbas Kaja , Medley Graham , Knight Gwenan M. , Gasparrini Antonio , Lowe Rachel
Published: October 2021

There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.
Specialized transendothelial dendritic cells mediate thymic T-cell selection against blood-borne macromolecules
Authors: Vollmann Elisabeth H. , Rattay Kristin , Barreiro Olga , Thiriot Aude , Fuhlbrigge Rebecca A. , Vrbanac Vladimir , Kim Ki-Wook , Jung Steffen , Tager Andrew M. , von Andrian Ulrich H.
Published: October 2021

T cells undergo rigorous selection in the thymus to ensure self-tolerance and prevent autoimmunity, with this process requiring innocuous self-antigens (Ags) to be presented to thymocytes. Self-Ags are either expressed by thymic stroma cells or transported to the thymus from the periphery by migratory dendritic cells (DCs); meanwhile, small blood-borne peptides can access the thymic parenchyma by diffusing across the vascular lining. Here we describe an additional pathway of thymic Ag acquisition that enables circulating antigenic macromolecules to access both murine and human thymi. This pathway depends on a subset of thymus-resident DCs, distinct from both parenchymal and circulating migratory DCs, that are positioned in immediate proximity to thymic microvessels where they extend cellular processes across the endothelial barrier into the blood stream. Transendothelial positioning of DCs depends on DC-expressed CX3CR1 and its endothelial ligand, CX3CL1, and disrupting this chemokine pathway prevents thymic acquisition of circulating proteins and compromises negative selection of Ag-reactive thymocytes. Thus, transendothelial DCs represent a mechanism by which the thymus can actively acquire blood-borne Ags to induce and maintain central tolerance.
Temperature dependence of quantum oscillations from non-parabolic dispersions
Authors: Guo Chunyu , Alexandradinata A. , Putzke Carsten , Estry Amelia , Tu Teng , Kumar Nitesh , Fan Feng-Ren , Zhang Shengnan , Wu Quansheng , Yazyev Oleg V. , Shirer Kent R. , Bachmann Maja D. , Peng Hailin , Bauer Eric D. , Ronning Filip , Sun Yan , Shekhar Chandra , Felser Claudia , Moll Philip J. W.
Published: October 2021

The phase offset of quantum oscillations is commonly used to experimentally diagnose topologically nontrivial Fermi surfaces. This methodology, however, is inconclusive for spin-orbit-coupled metals where π-phase-shifts can also arise from non-topological origins. Here, we show that the linear dispersion in topological metals leads to a T2-temperature correction to the oscillation frequency that is absent for parabolic dispersions. We confirm this effect experimentally in the Dirac semi-metal Cd3As2 and the multiband Dirac metal LaRhIn5. Both materials match a tuning-parameter-free theoretical prediction, emphasizing their unified origin. For topologically trivial Bi2O2Se, no frequency shift associated to linear bands is observed as expected. However, the π-phase shift in Bi2O2Se would lead to a false positive in a Landau-fan plot analysis. Our frequency-focused methodology does not require any input from ab-initio calculations, and hence is promising for identifying correlated topological materials.
Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells
Authors: Zhang Cheng , Zhu Hongyuan , Ren Xinru , Gao Bin , Cheng Bo , Liu Shaobao , Sha Baoyong , Li Zhaoqing , Zhang Zheng , Lv Yi , Wang Haohua , Guo Hui , Lu Tian Jian , Xu Feng , Genin Guy M. , Lin Min
Published: October 2021

Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell’s mechanical microenvironment changes substantially over the course of development, beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed “mechanical memory” in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems.
Quantitative 3D imaging of the cranial microvascular environment at single-cell resolution
Authors: Rindone Alexandra N. , Liu Xiaonan , Farhat Stephanie , Perdomo-Pantoja Alexander , Witham Timothy F. , Coutu Daniel L. , Wan Mei , Grayson Warren L.
Published: October 2021

Vascularization is critical for skull development, maintenance, and healing. Yet, there remains a significant knowledge gap in the relationship of blood vessels to cranial skeletal progenitors during these processes. Here, we introduce a quantitative 3D imaging platform to enable the visualization and analysis of high-resolution data sets (>100 GB) throughout the entire murine calvarium. Using this technique, we provide single-cell resolution 3D maps of vessel phenotypes and skeletal progenitors in the frontoparietal cranial bones. Through these high-resolution data sets, we demonstrate that CD31hiEmcnhi vessels are spatially correlated with both Osterix+ and Gli1+ skeletal progenitors during postnatal growth, healing, and stimulated remodeling, and are concentrated at transcortical canals and osteogenic fronts. Interestingly, we find that this relationship is weakened in mice with a conditional knockout of PDGF-BB in TRAP+ osteoclasts, suggesting a potential role for osteoclasts in maintaining the native cranial microvascular environment. Our findings provide a foundational framework for understanding how blood vessels and skeletal progenitors spatially interact in cranial bone, and will enable more targeted studies into the mechanisms of skull disease pathologies and treatments. Additionally, our technique can be readily adapted to study numerous cell types and investigate other elusive phenomena in cranial bone biology.
Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo
Authors: Hitchings Matt D. T. , Ranzani Otavio T. , Dorion Murilo , D’Agostini Tatiana Lang , de Paula Regiane Cardoso , de Paula Olivia Ferreira Pereira , de Moura Villela Edlaine Faria , Torres Mario Sergio Scaramuzzini , de Oliveira Silvano Barbosa , Schulz Wade , Almiron Maria , Said Rodrigo , de Oliveira Roberto Dias , Silva Patricia Vieira , de Araújo Wildo Navegantes , Gorinchteyn Jean Carlo , Andrews Jason R. , Cummings Derek A. T. , Ko Albert I. , Croda Julio
Published: October 2021

A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4–39.7) against Covid-19, 55.1% (95% CI, 46.6–62.2) against hospitalization, and 61.8% (95% CI, 48.9–71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2–84.2) against Covid-19, 87.6% (95% CI, 78.2–92.9) against hospitalization, and 93.6% (95% CI, 81.9–97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation.
The impact of the timely birth dose vaccine on the global elimination of hepatitis B
Authors: de Villiers Margaret J. , Nayagam Shevanthi , Hallett Timothy B.
Published: October 2021

In 2016 the World Health Organization set the goal of eliminating hepatitis B globally by 2030. Horizontal transmission has been greatly reduced in most countries by scaling up coverage of the infant HBV vaccine series, and vertical transmission is therefore becoming increasingly dominant. Here we show that scaling up timely hepatitis B birth dose vaccination to 90% of new-borns in 110 low- and middle-income countries by 2030 could prevent 710,000 (580,000 to 890,000) deaths in the 2020 to 2030 birth cohorts compared to status quo, with the greatest benefits in Africa. Maintaining this could lead to elimination by 2030 in the Americas, but not before 2059 in Africa. Drops in coverage due to disruptions in 2020 may lead to 15,000 additional deaths, mostly in South-East Asia and the Western Pacific. Delays in planned scale-up could lead to an additional 580,000 deaths globally in the 2020 to 2030 birth cohorts.
Congenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5
Authors: Linders Peter T. A. , Gerretsen Eveline C. F. , Ashikov Angel , Vals Mari-Anne , de Boer Rinse , Revelo Natalia H. , Arts Richard , Baerenfaenger Melissa , Zijlstra Fokje , Huijben Karin , Raymond Kimiyo , Muru Kai , Fjodorova Olga , Pajusalu Sander , Õunap Katrin , ter Beest Martin , Lefeber Dirk , van den Bogaart Geert
Published: October 2021

The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two protein isoforms, Stx5 Long (Stx5L) from the first starting methionine and Stx5 Short (Stx5S) from an alternative starting methionine at position 55. In this study, we identify a human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform. Patients suffer from an early fatal multisystem disease, including severe liver disease, skeletal abnormalities and abnormal glycosylation. Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking. Measurements of cognate binding SNAREs, based on biotin-synchronizable forms of Stx5 (the RUSH system) and Förster resonance energy transfer (FRET), revealed that the short isoform of Stx5 is essential for intra-Golgi transport. Alternative starting codons of Stx5 are thus linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking.
Partially overlapping spatial environments trigger reinstatement in hippocampus and schema representations in prefrontal cortex
Authors: Zheng Li , Gao Zhiyao , McAvan Andrew S. , Isham Eve A. , Ekstrom Arne D.
Published: October 2021

When we remember a city that we have visited, we retrieve places related to finding our goal but also non-target locations within this environment. Yet, understanding how the human brain implements the neural computations underlying holistic retrieval remains unsolved, particularly for shared aspects of environments. Here, human participants learned and retrieved details from three partially overlapping environments while undergoing high-resolution functional magnetic resonance imaging (fMRI). Our findings show reinstatement of stores even when they are not related to a specific trial probe, providing evidence for holistic environmental retrieval. For stores shared between cities, we find evidence for pattern separation (representational orthogonalization) in hippocampal subfield CA2/3/DG and repulsion in CA1 (differentiation beyond orthogonalization). Additionally, our findings demonstrate that medial prefrontal cortex (mPFC) stores representations of the common spatial structure, termed schema, across environments. Together, our findings suggest how unique and common elements of multiple spatial environments are accessed computationally and neurally.
Analyzing the performance of variational quantum factoring on a superconducting quantum processor
Authors: Karamlou Amir H. , Simon William A. , Katabarwa Amara , Scholten Travis L. , Peropadre Borja , Cao Yudong
Published: October 2021

In the near-term, hybrid quantum-classical algorithms hold great potential for outperforming classical approaches. Understanding how these two computing paradigms work in tandem is critical for identifying areas where such hybrid algorithms could provide a quantum advantage. In this work, we study a QAOA-based quantum optimization approach by implementing the Variational Quantum Factoring (VQF) algorithm. We execute experimental demonstrations using a superconducting quantum processor, and investigate the trade off between quantum resources (number of qubits and circuit depth) and the probability that a given biprime is successfully factored. In our experiments, the integers 1099551473989, 3127, and 6557 are factored with 3, 4, and 5 qubits, respectively, using a QAOA ansatz with up to 8 layers and we are able to identify the optimal number of circuit layers for a given instance to maximize success probability. Furthermore, we demonstrate the impact of different noise sources on the performance of QAOA, and reveal the coherent error caused by the residual ZZ-coupling between qubits as a dominant source of error in a near-term superconducting quantum processor.
Cognitive, creative, functional, and clinical symptom improvements in schizophrenia after an integrative cognitive remediation program: a randomized controlled trial
Authors: Sampedro Agurne , Peña Javier , Sánchez Pedro , Ibarretxe-Bilbao Naroa , Gómez-Gastiasoro Ainara , Iriarte-Yoller Nagore , Pavón Cristóbal , Tous-Espelosin Mikel , Ojeda Natalia
Published: October 2021

This study analyzed the effectiveness of an integrative cognitive remediation program (REHACOP) in improving neurocognition, social cognition, creativity, functional outcome, and clinical symptoms in patients with schizophrenia. In addition, possible mediators predicting improvement in functional outcomes were explored. The program combined cognitive remediation with social cognitive training and social and functional skill training over 20 weeks. The sample included 94 patients, 47 in the REHACOP group and 47 in the active control group (occupational activities). Significant differences were found between the two groups in change scores of processing speed, working memory, verbal memory (VM), inhibition, theory of mind, emotion processing (EP), figural creative strengths, functional competence, disorganization, excitement, and primary negative symptoms. A mediational analysis revealed that changes in VM, inhibition, and EP partially explained the effect of cognitive remediation on functional competence improvement. This study provides initial evidence of the effect of integrative cognitive remediation on primary negative symptoms and creativity.
Exploiting viral sensing mediated by Toll-like receptors to design innovative vaccines
Authors: Sartorius Rossella , Trovato Maria , Manco Roberta , D’Apice Luciana , De Berardinis Piergiuseppe
Published: October 2021

Toll-like receptors (TLRs) are transmembrane proteins belonging to the family of pattern-recognition receptors. They function as sensors of invading pathogens through recognition of pathogen-associated molecular patterns. After their engagement by microbial ligands, TLRs trigger downstream signaling pathways that culminate into transcriptional upregulation of genes involved in immune defense. Here we provide an updated overview on members of the TLR family and we focus on their role in antiviral response. Understanding of innate sensing and signaling of viruses triggered by these receptors would provide useful knowledge to prompt the development of vaccines able to elicit effective and long-lasting immune responses. We describe the mechanisms developed by viral pathogens to escape from immune surveillance mediated by TLRs and finally discuss how TLR/virus interplay might be exploited to guide the design of innovative vaccine platforms.