bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory gating, neurocognition, social cognition and real-life functioning: a 2-year follow-up of early psychosis
Authors: Li Shen , Chan Shi Yu , Higgins Amy , Hall Mei-Hua
Published: November 2021

Background

Diminished sensory gating (SG) is a robust finding in psychotic disorders, but studies of early psychosis (EP) are rare. It is unknown whether SG deficit leads to poor neurocognitive, social, and/or real-world functioning. This study aimed to explore the longitudinal relationships between SG and these variables.

Methods

Seventy-nine EP patients and 88 healthy controls (HCs) were recruited at baseline. Thirty-three and 20 EP patients completed 12-month and 24-month follow-up, respectively. SG was measured using the auditory dual-click (S1 & S2) paradigm and quantified as P50 ratio (S2/S1) and difference (S1-S2). Cognition, real-life functioning, and symptoms were assessed using the MATRICS Consensus Cognitive Battery, Global Functioning: Social (GFS) and Role (GFR), Multnomah Community Ability Scale (MCAS), Awareness of Social Inference Test (TASIT), and the Positive and Negative Syndrome Scale (PANSS). Analysis of variance (ANOVA), chi-square, mixed model, correlation and regression analyses were used for group comparisons and relationships among variables controlling for potential confounding variables.

Results

In EP patients, P50 ratio (p < 0.05) and difference (p < 0.001) at 24-month showed significant differences compared with that at baseline. At baseline, P50 indices (ratio, S1-S2 difference, S1) were independently associated with GFR in HCs (all p < 0.05); in EP patients, S2 amplitude was independently associated with GFS (p = 0.037). At 12-month and 24-month, P50 indices (ratio, S1, S2) was independently associated with MCAS (all p < 0.05). S1-S2 difference was a trending predictor of future function (GFS or MCAS).

Conclusions

SG showed progressive reduction in EP patients. P50 indices were related to real-life functioning.
Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits
Authors: Otsuka Ikuo , Galfalvy Hanga , Guo Jia , Akiyama Masato , Rujescu Dan , Turecki Gustavo , Hishimoto Akitoyo , Mann J. John
Published: November 2021

Background

Suicidal behavior is moderately heritable and a consequence of a combination of the diathesis traits for suicidal behavior and suicide-related major psychiatric disorders. Here, we sought to examine shared polygenic effects between various psychiatric disorders/traits and suicidal behavior and to compare the shared polygenic effects of various psychiatric disorders/traits on non-fatal suicide attempt and suicide death.

Methods

We used our genotyped European ancestry sample of 260 non-fatal suicide attempters, 317 suicide decedents and 874 non-psychiatric controls to test whether polygenic risk scores (PRSs) obtained from large GWASs for 22 suicide-related psychiatric disorders/traits were associated with suicidal behavior. Results were compared between non-fatal suicide attempt and suicide death in a sensitivity analysis.

Results

PRSs for major depressive disorder, bipolar disorder, schizophrenia, ADHD, alcohol dependence, sensitivity to environmental stress and adversity, educational attainment, cognitive performance, and IQ were associated with suicidal behavior (Bonferroni-corrected p < 2.5 × 10−4). The polygenic effects of all 22 psychiatric disorders/traits had the same direction (p for binomial tests = 4.8 × 10−7) and were correlated (Spearman's ρ = 0.85) between non-fatal suicide attempters and suicide decedents.

Conclusions

We found that polygenic effects for major psychiatric disorders and diathesis-related traits including stress responsiveness and intellect/cognitive function contributed to suicidal behavior. While we found comparable polygenic architecture between non-fatal suicide attempters and suicide decedents based on correlations with PRSs of suicide-related psychiatric disorders/traits, our analyses are limited by small sample size resulting in low statistical power to detect difference between non-fatal suicide attempt and suicide death.
RIVERBED, BANKS AND BEYOND: AN EXAMINATION OF ROMAN INFRASTRUCTURE AND INTERVENTIONS IN RESPONSE TO HYDROLOGICAL RISK IN THE PO–VENETIAN PLAIN
Authors: Page James
Published: November 2021

Water poses a particular challenge to the cities and settlements of the Po–Venetian plain. The region has some of the highest levels of precipitation in Italy and is criss-crossed by dozens of rivers, including the Po, Adige and Tagliamento. Throughout history, there was considerable hydrological risk to the well-being of riparian communities from hazards such as flooding and lateral channel movement, yet local residents did not sit idly by. This article synthesizes the available evidence for Roman responses to hydrological risk in the Po–Venetian plain from the first century BC to the sixth century AD, examining their workings and the hazards they sought to counteract, integrating them into wider discussions on risk in the Roman world. The responses are divided into the categories of defensive works (embankments and dykes) and channel interventions (channel rectification, channel diversion and dredging). While the effectiveness of these methods is questioned, in particular their potential to cause unintended changes to the watercourse, the decision by riparian communities to undertake them suggests a degree of local success. Nevertheless, an examination of the archaeological and palaeoclimatic evidence suggests a discrepancy between peak intervention and peak risk, implying increasing vulnerability and risk acceptance amongst riparian communities during late antiquity.
Interpersonal dysfunction in individuals high in chronic worry: relations with interpersonal problem-solving
Authors: Malivoire Bailee L. , Koerner Naomi
Published: November 2021

Background:

Interpersonal dysfunction has been proposed as an important maintenance factor in chronic worry and generalized anxiety disorder (GAD). Perceptions of problems and the problem-solving process as threatening, and unhelpful (e.g. avoidant, impulsive) problem-solving styles are implicated in worry and have also been suggested to be associated with dysfunctional interpersonal styles.

Aims:

The present study assessed the relationships between interpersonal dysfunction and problem-solving orientation, approach, and effectiveness in a sample of individuals high in chronic worry and investigated the indirect effect of interpersonal dysfunction on GAD symptom severity through negative problem-solving beliefs and approaches.

Method:

Fifty-nine community participants completed questionnaires and an interpersonal problem-solving task.

Results:

Greater interpersonal dysfunction was significantly associated with greater negative problem-solving orientation and greater habitual avoidant and impulsive/careless problem-solving styles. Greater interpersonal dysfunction was associated with poorer effectiveness of solutions when the task problem involved conflict with a romantic partner. Negative problem-solving orientation fully mediated the relationship between interpersonal dysfunction and GAD symptoms.

Conclusions:

These findings support that problem-solving processes are implicated in interpersonal dysfunction and that negative beliefs about problem-solving account for the relationship between interpersonal dysfunction and GAD symptoms. Theoretical implications are discussed.
Using 360-degree videos for virtual reality exposure in CBT for panic disorder with agoraphobia: a feasibility study
Authors: Lundin Johan , Lundström Anders , Gulliksen Jan , Blendulf Joakim , Ejeby Kersti , Nyman Hedda , Björkander Daniel , Hedman-Lagerlöf Erik
Published: November 2021

Background:

Cognitive behavioural therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PDA). However, implementation of some of the procedures involved, particularly in vivo exposure, can be time consuming and taxing for routine health care services. CBT with exposure taking place in virtual reality (VR-CBT) is a more time-efficient option and has shown promising results in the treatment of PDA. However, VR-CBT requires expensive equipment and appropriate virtual environments, which historically has been costly and cumbersome to produce. Thus, access to VR-CBT has been sparse in regular care environments.

Aims:

The aim of this study was to investigate whether VR-CBT using filmed virtual environments produced with a low-cost 360-degree film camera can be a feasible and acceptable treatment for PDA when implemented in a primary care context.

Method:

This was an open feasibility trial with a within-group design, with assessments conducted at pre-test, post-test, and 6-month follow-up. Participants (n = 12) received a 10–12 week treatment programme of VR-CBT and PDA-related symptoms were assessed by the primary outcome measure The Mobility Inventory for Agoraphobia (MIA) and the Panic-Disorder Severity Scale-Self Rated (PDSS-SR).

Results:

The results showed that treatment satisfaction was high and participants were significantly improved on PDA-related measures at post-treatment and at 6-month follow-up with large effect sizes (Cohen’s d range = 1.46–2.82). All 12 participants completed the treatment.

Conclusions:

These findings suggest that VR-CBT with 360-degree video virtual environments delivered to primary care patients with PDA is feasible, acceptable, and potentially efficacious.
Illiberal Communication and Election Intervention during the Refugee Crisis in Germany
Authors: Elshehawy Ashrakat , Gavras Konstantin , Marinov Nikolay , Nanni Federico , Schoen Harald
Published: November 2021

Populist discourse—which tends to benefit anti-systemic parties—has been on the rise in the world’s democratic states. Powerful non-democratic states have both the means and the incentive to spread such discourse to democratic states. We clarify the incentives illiberal states have to produce such communication, and delineate how this type of political communication fuses traditional state-to-state propaganda with election interventions. We draw on the case of Kremlin-sponsored communication on the issue of refugees in Germany to illustrate the mechanisms through which the discourse operates in target countries. We create a corpus of over a million news stories to identify the prevalence of illiberal discourse and its timing relative to Germany’s elections. We show that the Kremlin intervened in the 2017 federal elections by promoting refugee stories over and above the rate at which German outlets did. We discuss the broader implications for the use of directed political communication as a form of election intervention.
Stufen der Veränderung
Authors: Hieke André
Published: November 2021

Was ist zu diesem Thema bereits bekannt?

Der Einsatz des in England entwickelten Assessmentinstruments ist derzeit begrenzt auf bestimmte englischsprachige Länder, wo es von vielen Einrichtungen genutzt wird, um Menschen mit einer Vielzahl von kurz- und langfristigen psychischen Problemen zu unterstützen. Im deutschsprachigen Raum, insbesondere in Deutschland, werden die Recovery-Stars™ bisher nicht verwendet.

Wie wird eine neue Perspektive eingebracht?

Mithilfe des MHRS™ und seiner zehn Bereiche (siehe Abbildung 1) lässt sich deutlich erkennen, auf welcher Entwicklungsstufe ein Betroffener sich gerade befindet. Der MHRS™ hilft den Betroffenen, das Ganze zu sehen und macht es für die professionell Tätigen leichter, die jeweiligen Veränderungen oder Stagnationen im Behandlungsprozess sichtbar zu machen. Aus Sicht des Verfassers ist der MHRS™ eine Bewertungshilfe und ein Messinstrument für Behandlungserfolge in der recovery-orientierten psychiatrischen Versorgung.

Was sind die Auswirkungen auf die Praxis?

Verschiedene Konzepte wie die Bezugspersonenpflege und das Recovery-Konzept wirbeln das klassische Rollenverständnis von professionell Tätigen in der Psychiatrie (Pflegenden, Psycholog_innen, Ärzt_innen) durcheinander. Psychisch erkrankte Menschen und professionell Tätige rücken bei beiden Konzepten näher zusammen und werden gleichberechtigte Partner im Behandlungs- und Unterstützungsprozess. Mithilfe des MHRS™ steht der oder die Betroffene im Mittelpunkt der Behandlung, denn nur er oder sie entscheidet, wohin der Weg geht. Die professionell Tätigen unterstützen ihn oder sie im Rahmen ihrer Möglichkeiten.
A Theory of Media Multitasking Intensity
Authors: Zamanzadeh Nicole N. , Rice Ronald E.
Published: November 2021

Abstract. This article first situates media multitasking in the changing media ecology. Then, grounded in concepts of stress and flow, limited capacity, and threaded cognition, it develops a four-dimensional theory of media multitasking intensity. Based on the key aspects of media multitasking intensity, the subsequent section proposes two primary influences (executive functioning and self-regulation) and one primary outcome (general stress). An application example focuses on several media multitasking issues and the stress outcome for adolescents within their family environment. The final section suggests a few key methodological implications for studying the theory of media multitasking intensity (self-report, and both temporal and social contexts). The theory of media multitasking intensity generates insights about the functional (i.e., valuable) variation within experiences of media as they overlap with and interrupt experiences of the physical and mediated world.
HAPI: An API Standard for Accessing Heliophysics Time Series Data
Authors: Weigel Robert S. , Vandegriff Jon , Faden Jeremy , King Todd , Roberts D Aaron , Harris Bernard , Candey Robert , Lal Nand , Boardsen Scott , Lindholm Chris , Lindholm Doug , Baltzer Thomas , Brown Lawrence E. , Grimes Eric W. , Cecconi Baptiste , Génot Vincent , Renard Benjamin , Masson Arnaud , Martinez Beatriz
Published: November 2021

Heliophysics data analysis often involves combining diverse science measurements, many of them captured as time series. Although there are now only a few commonly used data file formats, the diversity in mechanisms for automated access to and aggregation of such data holdings can make analysis that requires intercomparison of data from multiple data providers difficult. The Heliophysics Application Programmer's Interface (HAPI) is a recently developed standard for accessing distributed time series data to increase interoperability. The HAPI specification is based on the common elements of existing data services, and it standardizes the two main parts of a data service: the request interface and the response data structures. The interface is based on the REpresentational State Transfer (REST) or RESTful architecture style, and the HAPI specification defines five required REST endpoints. Data are returned via a streaming format that hides file boundaries; the metadata is detailed enough for the content to be scientifically useful, e.g., plotted with appropriate axes layout, units, and labels. Multiple mature HAPI‐related open‐source projects offer server‐side implementation tools and client‐side libraries for reading HAPI data in multiple languages (IDL, Java, MATLAB, and Python). Multiple data providers in the US and Europe have added HAPI access alongside their existing interfaces. Based on this experience, data can be served via HAPI with little or no information loss compared to similar existing web interfaces. Finally, HAPI has been recommended as a COSPAR standard for time series data delivery.
Structural and Thermal Evolution of an Infant Subduction Shear Zone: Insights From Sub‐Ophiolite Metamorphic Rocks Recovered From Oman Drilling Project Site BT‐1B
Authors: Kotowski Alissa J. , Cloos Mark , Stockli Daniel F. , Bos Orent Eytan
Published: November 2021

Subduction interface thermal structure changes drastically within the first few million years of underthrusting (i.e., subduction infancy). Metamorphic soles beneath ophiolites record snapshots of dynamic conditions and mechanical coupling during subduction infancy. Beneath the Samail Ophiolite (Oman), the sole comprises structurally higher high‐temperature (HT) and lower low‐temperature (LT) units. This inverted metamorphic gradient has been attributed to evolving metamorphic Pressure‐Temperature (P‐T) conditions during infancy; however, peak P‐T and timing of LT sole subduction are poorly constrained. Oman Drilling Project core BT‐1B sampled the base of the ophiolite in a location lacking the HT sole. Metasedimentary and meta‐mafic samples collected from 104 m of core reveal that the LT sole subducted to similar peak P as HT rocks preserved elsewhere in Oman, but experienced ∼300°C lower peak T. Prograde fabrics record Si‐in‐phengite and amphibole chemistries consistent with peak P‐T of ∼7–10 kbar and ∼450–550°C in the epidote‐amphibolite facies. Retrograde fabrics record a transition from near‐pervasive ductile to localized brittle strain under greenschist facies conditions. Titanite U‐Pb ages (n = 2) constrain timing of peak LT sole subduction to ∼91 Ma (post‐dating initial HT sole subduction by ∼12–13 Myr) and dynamic retrogression through ∼90 Ma. Combined with existing geo/thermo‐chronology, our results support a model of protracted subduction and accretion while the infant subduction zone experienced multi‐phase, slow‐fast‐slow cooling. Temporal overlap of HT sole cooling (rehydration?) and ophiolite formation suggests that cooling may lead to interface weakening, facilitating upper‐plate extension and spreading. The LT sole formed in a rapidly‐refrigerating forearc after ophiolite formation and may reflect the transition to self‐sustaining subduction.
Intra‐Annual Variation of Eddy Diffusion (kzz) in the MLT, From SABER and SCIAMACHY Atomic Oxygen Climatologies
Authors: Swenson G. R. , Vargas F. , Jones M. , Zhu Y. , Kaufmann M. , Yee J. H. , Mlynczak M.
Published: November 2021

Atomic oxygen (O) in the mesosphere and lower thermosphere (MLT) results from a balance between production via photo‐dissociation in the lower thermosphere and chemical loss by recombination in the upper mesosphere. The transport of O downward from the lower thermosphere into the mesosphere is preferentially driven by the eddy diffusion process that results from dissipating gravity waves and instabilities. The motivation here is to probe the intra‐annual variability of the eddy diffusion coefficient (kzz) and eddy velocity in the MLT based on the climatology of the region, initially accomplished by Garcia and Solomon (1985, https://doi.org/10.1029/JD090iD02p03850). In the current study, the intra‐annual cycle was divided into 26 two‐week periods for each of three zones: the northern hemisphere (NH), southern hemisphere (SH), and equatorial (EQ). Both 16 years of SABER (2002–2018) and 10 years of SCIAMACHY (2002–2012) O density measurements, along with NRLMSIS® 2.0 were used for calculation of atomic oxygen eddy diffusion velocities and fluxes. Our prominent findings include a dominant annual oscillation below 87 km in the NH and SH zones, with a factor of 3–4 variation between winter and summer at 83 km, and a dominant semiannual oscillation at all altitudes in the EQ zone. The measured global average kzz at 96 km lacks the intra‐annual variability of upper atmosphere density data deduced by Qian et al. (2009, https://doi.org/10.1029/2008JA013643). The very large seasonal (and hemispherical) variations in kzz and O densities are important to separate and isolate in satellite analysis and to incorporate in MLT models.
Modeling the Sulfate Aerosol Evolution After Recent Moderate Volcanic Activity, 2008–2012
Authors: Brodowsky Christina , Sukhodolov Timofei , Feinberg Aryeh , Höpfner Michael , Peter Thomas , Stenke Andrea , Rozanov Eugene
Published: November 2021

Volcanic activity is a major natural climate forcing and an accurate representation of volcanic aerosols in global climate models is essential. This is a complex task involving many uncertainties in the model design and setup and observations. We analyze the performance of the aerosol‐chemistry‐climate model SOCOL‐AERv2 for three medium‐sized volcanic eruptions. We focus on the impact of differences in volcanic plume height and SO2 estimates on the stratospheric aerosol burden. The influence of internal model variability and dynamics are addressed through an ensemble of free‐running and nudged simulations at different vertical resolutions. Comparing the modeled evolution of the stratospheric aerosol loading to satellite measurements reveals a good model performance. However, a conclusive validation is complicated by uncertainties in observations and emission estimates. The large spread in emitted sulfur amount and its vertical distribution consequently lead to differences in simulated aerosol burdens. Varying tropopause heights among free‐running simulations add to these differences, modulating the amount of sulfur injected into the stratosphere. In nudged mode, volcanic aerosol burden peaks are well reproduced, however changes in convection and clouds affect SO2 oxidation paths and cross‐tropopause transport, leading to increased background burdens compared to observations. This effect can be reduced by leaving temperatures unconstrained. A higher vertical resolution of 90 levels increases the stratospheric residence time of sulfate aerosol by reducing the diffusion out of the tropical reservoir. We conclude that the model set‐up (vertical resolution and free‐running vs. nudged) as well as forcing parameters (volcanic emission strength and plume height) contribute equally to the model uncertainties.
Impacts of Bias‐Corrected ERA5 Initial Snow Depth on Dynamical Downscaling Simulations for the Tibetan Plateau
Authors: Lin Qian , Chen Jie , Chen Deliang , Wang Xun , Li Wei , Scherer Dieter
Published: November 2021

The Tibetan Plateau (TP) is often called the “Water Tower of Asia,” which contains the largest amount of snow and glaciers outside the polar regions. As an important and variable feature of the land surface, snow coverage on the TP has great impacts on regional climate. However, the commonly used ERA5 reanalysis in dynamical downscaling largely overestimates the snow depth for the TP. To improve the representation of snow cover in ERA5, a new ERA5‐driven downscaling data set (High Asia Refined analysis version 2, HAR v2) was generated by the Weather Research and Forecasting (WRF) model with the bias‐corrected snow depth. This study aims to identify and better understand the impact of bias‐corrected initial snow conditions on simulated regional climate, by comparing the HAR v2 with a 5‐year ERA5 forced WRF simulation without bias correction of initial snow depth (referred to as WRF_ERA5). The results show that the bias correction significantly improves the simulation of 2 m air temperature (T2), with regional mean cold bias reduced by 0.2°C–2.4°C, but no significant improvement in precipitation simulation is found. Further comparative analysis reveals that higher snow depth in WRF_ERA5 leads to T2, mean daily precipitation, summer extreme precipitation, and contributions of convective precipitation to summer mean daily precipitation decrease by 0°C–4°C, 0%–60%, 0%–40%, and 0%–10%, respectively, in most areas of the TP. In addition, the bias‐corrected initial snow depth also has impacts on simulated diurnal cycles of precipitation and T2 and leads to peak hours one hour earlier. Overall, this study confirms the importance of snow cover for the climate in the TP.
The Onset of a Globally Ice‐Covered State for a Land Planet
Authors: Kodama T. , Genda H. , Leconte J. , Abe‐Ouchi A.
Published: November 2021

The climates of terrestrial planets with a small amount of water on their surface, called land planets, are significantly different from the climates of planets having a large amount of surface water. Land planets have a higher runaway greenhouse threshold than aqua planets, which extends the inner edge of the habitable zone inward. Land planets also have the advantage of avoiding global freezing due to drier tropics, leading to a lower planetary albedo. In this study, we systematically investigate the complete freezing limit for various surface water distributions using a three‐dimensional dynamic atmospheric model. As in a previous study, we found that a land planet climate has dry tropics that result in less snow and fewer clouds. The complete freezing limit decreases from that for aqua planets (92% S0, where S0 is Earth's present insolation) to that for land planets (77% S0) with an increasing dry area. Values for the complete freezing limit for zonally uniform surface water distributions are consistently lower than those for meridionally uniform surface water distribution. This is because the surface water distribution in the tropics in the meridionally uniform cases causes ice‐albedo feedback until a planet lapses into the complete freezing state. For a surface water distribution using the topographies of the terrestrial planets, the complete freezing limit has values near those for the meridionally uniform cases. Our results indicate that the water distribution is important for the onset of a global ice‐covered state for Earth‐like exoplanets.
Fidelity of the Coral Sr/Ca Paleothermometer Following Heat Stress in the Northern Galápagos
Authors: Cheung Anson H. , Cole Julia E. , Thompson Diane M. , Vetter Lael , Jimenez Gloria , Tudhope Alexander W.
Published: November 2021

Coral Sr/Ca records have been widely used to reconstruct and understand past sea surface temperature (SST) variability in the tropical Pacific. However, in the eastern equatorial Pacific, coral growth conditions are marginal, and strong El Niño events have led to high mortality, limiting opportunities for coral Sr/Ca‐based SST reconstructions. In this study, we present two ∼25‐year Sr/Ca and Mg/Ca records measured on modern Porites lobata from Wolf and Darwin Islands in the northern Galápagos. In these records, we confirm the well‐established relationship between Sr/Ca and SST and investigate the impact of heat stress on this relationship. We demonstrate a weakened relationship between Sr/Ca and SST after a major (Degree Heating Months 9°C‐months) heat stress event during the 1997–1998 El Niño, with a larger response in the Wolf core. However, removing data that covers the 1997–1998 El Niño from calibration does not improve reconstruction statistics. Nevertheless, we find that excluding data after the 1997–1998 El Niño event from the calibration reduces the SST reconstruction error slightly. These results confirm that coral Sr/Ca is a reliable SST proxy in this region, although it can respond adversely to unusual heat stress. We suggest that noise in Sr/Ca‐SST calibrations may be reduced by removing data immediately following large heat extremes.
Biopsy-free in vivo virtual histology of skin using deep learning
Authors: Li Jingxi , Garfinkel Jason , Zhang Xiaoran , Wu Di , Zhang Yijie , de Haan Kevin , Wang Hongda , Liu Tairan , Bai Bijie , Rivenson Yair , Rubinstein Gennady , Scumpia Philip O. , Ozcan Aydogan
Published: November 2021

An invasive biopsy followed by histological staining is the benchmark for pathological diagnosis of skin tumors. The process is cumbersome and time-consuming, often leading to unnecessary biopsies and scars. Emerging noninvasive optical technologies such as reflectance confocal microscopy (RCM) can provide label-free, cellular-level resolution, in vivo images of skin without performing a biopsy. Although RCM is a useful diagnostic tool, it requires specialized training because the acquired images are grayscale, lack nuclear features, and are difficult to correlate with tissue pathology. Here, we present a deep learning-based framework that uses a convolutional neural network to rapidly transform in vivo RCM images of unstained skin into virtually-stained hematoxylin and eosin-like images with microscopic resolution, enabling visualization of the epidermis, dermal-epidermal junction, and superficial dermis layers. The network was trained under an adversarial learning scheme, which takes ex vivo RCM images of excised unstained/label-free tissue as inputs and uses the microscopic images of the same tissue labeled with acetic acid nuclear contrast staining as the ground truth. We show that this trained neural network can be used to rapidly perform virtual histology of in vivo, label-free RCM images of normal skin structure, basal cell carcinoma, and melanocytic nevi with pigmented melanocytes, demonstrating similar histological features to traditional histology from the same excised tissue. This application of deep learning-based virtual staining to noninvasive imaging technologies may permit more rapid diagnoses of malignant skin neoplasms and reduce invasive skin biopsies.
A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents
Authors: Nishitani Shota , Fujisawa Takashi X. , Hiraoka Daiki , Makita Kai , Takiguchi Shinichiro , Hamamura Shoko , Yao Akiko , Shimada Koji , Smith Alicia K. , Tomoda Akemi
Published: November 2021

Child maltreatment dysregulates the brain’s oxytocinergic system, resulting in dysfunctional attachment patterns. However, how the oxytocinergic system in children who are maltreated (CM) is epigenetically affected remains unknown. We assessed differences in salivary DNA methylation of the gene encoding oxytocin (OXT) between CM (n = 24) and non-CM (n = 31), alongside its impact on brain structures and functions using multi-modal brain imaging (voxel-based morphometry, diffusion tensor imaging, and task and resting-state functional magnetic resonance imaging). We found that CM showed higher promoter methylation than non-CM, and nine CpG sites were observed to be correlated with each other and grouped into one index (OXTmi). OXTmi was significantly negatively correlated with gray matter volume (GMV) in the left superior parietal lobule (SPL), and with right putamen activation during a rewarding task, but not with white matter structures. Using a random forest regression model, we investigated the sensitive period and type of maltreatment that contributed the most to OXTmi in CM, revealing that they were 5–8 years of age and physical abuse (PA), respectively. However, the presence of PA (PA+) was meant to reflect more severe cases, such as prolonged exposure to multiple types of abuse, than the absence of PA. PA+ was associated with significantly greater functional connectivity between the right putamen set as the seed and the left SPL and the left cerebellum exterior. The results suggest that OXT promoter hypermethylation may lead to the atypical development of reward and visual association structures and functions, thereby potentially worsening clinical aspects raised by traumatic experiences.
Inhibition of DTYMK significantly restrains the growth of HCC and increases sensitivity to oxaliplatin
Authors: Sun Fengze , Liu Yuanyuan , Gong Tingting , Pan Qiuzhong , Xiang Tong , Zhao Jingjing , Tang Yan , Chen Hao , Han Yulong , Song Mengjia , Huang Yue , Li Han , Chen Yuanyuan , Yang Chaopin , Yang Jieying , Wang Qijing , Li Yongqiang , He Jia , Weng Desheng , Peng Ruiqing , Xia Jianchuan
Published: November 2021

Most patients with hepatocellular carcinoma (HCC) are in the middle or advanced stage at the time of diagnosis, and the therapeutic effect is limited. Therefore, this study aimed to verify whether deoxythymidylate kinase (DTYMK) increased in HCC and was an effective therapeutic target in HCC. The findings revealed that the DTYMK level significantly increased and correlated with poor prognosis in HCC. However, nothing else is known, except that DTYMK could catalyze the phosphorylation of deoxythymidine monophosphate (dTMP) to form deoxythymidine diphosphate (dTDP). A number of experiments were performed to study the function of DTYMK in vitro and in vivo to resolve this knowledge gap. The knockdown of DTYMK was found to significantly inhibit the growth of HCC and increase the sensitivity to oxaliplatin, which is commonly used in HCC treatment. Moreover, DTYMK was found to competitively combine with miR-378a-3p to maintain the expression of MAPK activated protein kinase 2 (MAPKAPK2) and thus activate the phospho-heat shock protein 27 (phospho-HSP27)/nuclear factor NF-kappaB (NF-κB) axis, which mediated the drug resistance, proliferation of tumor cells, and infiltration of tumor-associated macrophages by inducing the expression of C-C motif chemokine ligand 5 (CCL5). Thus, this study demonstrated a new mechanism and provided a new insight into the role of mRNA in not only encoding proteins to regulate the process of life but also regulating the expression of other genes and tumor microenvironment through the competing endogenous RNA (ceRNA) mechanism.
Molecular and histological traits of reduced lysosomal acid lipase activity in the fatty liver
Authors: Carotti Simone , Lettieri-Barbato Daniele , Piemonte Fiorella , Ruggiero Sergio , Rosina Marco , Zalfa Francesca , Zingariello Maria , Arciprete Francesca , Valentini Francesco , Francesconi Maria , D’Amico Jessica , De Vincentis Antonio , Baiocchini Andrea , Perrone Giuseppe , Antonelli-Incalzi Raffaele , Morini Sergio , Picardi Antonio , Aquilano Katia , Vespasiani-Gentilucci Umberto
Published: November 2021

Recent studies demonstrated reduced blood lysosomal acid lipase (LAL) activity in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to verify hepatic LAL protein content and activity in in vitro and in vivo models of fat overload and in NAFLD patients. LAL protein content and activity were firstly evaluated in Huh7 cells exposed to high-glucose/high-lipid (HGHL) medium and in the liver of C57BL/6 mice fed with high-fat diet (HFD) for 4 and 8 months. LAL protein was also evaluated by immunohistochemistry in liver biopsies from 87 NAFLD patients and 10 controls, and correlated with hepatic histology. Huh7 cells treated with HGHL medium showed a significant reduction of LAL activity, which was consistent with reduced LAL protein levels by western blotting using an antibody towards the N-term of the enzyme. Conversely, antibodies towards the C-term of the enzyme evidenced LAL accumulation, suggesting a post-translational modification that masks the LAL N-term epitope and affects enzymatic activity. Indeed, we found a high rate of ubiquitination and extra-lysosomal localization of LAL protein in cells treated with HGHL medium. Consistent with these findings, inhibition of proteasome triggered dysfunctional LAL accumulation and affected LAL activity. Accumulation of ubiquitinated/dysfunctional LAL was also found in the liver of HFD fed mice. In NAFLD patients, hepatic levels of non-ubiquitinated/functional LAL were lower than in controls and inversely correlated with disease activity and some of the hallmarks of reduced LAL. Fat overload leads to LAL ubiquitination and impairs its function, possibly reducing hepatic fat disposal and promoting NAFLD activity.
Giant field-like torque by the out-of-plane magnetic spin Hall effect in a topological antiferromagnet
Authors: Kondou Kouta , Chen Hua , Tomita Takahiro , Ikhlas Muhammad , Higo Tomoya , MacDonald Allan H. , Nakatsuji Satoru , Otani YoshiChika
Published: November 2021

Spin-orbit torques (SOT) enable efficient electrical control of the magnetic state of ferromagnets, ferrimagnets and antiferromagnets. However, the conventional SOT has severe limitation that only in-plane spins accumulate near the surface, whether interpreted as a spin Hall effect (SHE) or as an Edelstein effect. Such a SOT is not suitable for controlling perpendicular magnetization, which would be more beneficial for realizing low-power-consumption memory devices. Here we report the observation of a giant magnetic-field-like SOT in a topological antiferromagnet Mn3Sn, whose direction and size can be tuned by changing the order parameter direction of the antiferromagnet. To understand the magnetic SHE (MSHE)- and the conventional SHE-induced SOTs on an equal footing, we formulate them as interface spin-electric-field responses and analyzed using a macroscopic symmetry analysis and a complementary microscopic quantum kinetic theory. In this framework, the large out-of-plane spin accumulation due to the MSHE has an inter-band origin and is likely to be caused by the large momentum-dependent spin splitting in Mn3Sn. Our work demonstrates the unique potential of antiferromagnetic Weyl semimetals in overcoming the limitations of conventional SOTs and in realizing low-power spintronics devices with new functionalities.
Dynamic transformation of cubic copper catalysts during CO2 electroreduction and its impact on catalytic selectivity
Authors: Grosse Philipp , Yoon Aram , Rettenmaier Clara , Herzog Antonia , Chee See Wee , Roldan Cuenya Beatriz
Published: November 2021

To rationally design effective and stable catalysts for energy conversion applications, we need to understand how they transform under reaction conditions and reveal their underlying structure-property relationships. This is especially important for catalysts used in the electroreduction of carbon dioxide where product selectivity is sensitive to catalyst structure. Here, we present real-time electrochemical liquid cell transmission electron microscopy studies showing the restructuring of copper(I) oxide cubes during reaction. Fragmentation of the solid cubes, re-deposition of new nanoparticles, catalyst detachment and catalyst aggregation are observed as a function of the applied potential and time. Using cubes with different initial sizes and loading, we further correlate this dynamic morphology with the catalytic selectivity through time-resolved scanning electron microscopy measurements and product analysis. These comparative studies reveal the impact of nanoparticle re-deposition and detachment on the catalyst reactivity, and how the increased surface metal loading created by re-deposited nanoparticles can lead to enhanced C2+ selectivity and stability.
Asymmetric radical carboesterification of dienes
Authors: Zhu Xiaotao , Jian Wujun , Huang Meirong , Li Daliang , Li Yajun , Zhang Xinhao , Bao Hongli
Published: November 2021

The straightforward strategy of building a chiral C-O bond directly on a general carbon radical center is challenging and stereocontrol of the reactions of open-chain hydrocarbon radicals remains a largely unsolved problem. Advance in this elementary step will spur the development of asymmetric radical C-O bond construction. Herein, we report a copper-catalyzed regioselective and enantioselective carboesterification of substituted dienes using alkyl diacyl peroxides as the source of both the carbon and oxygen substituents. The participation of external acids in this reaction substantially extends its applicability and leads to structurally diverse allylic ester products. This work represents the advance in the key elementary reaction of intermolecular enantioselective construction of C-O bond on open-chain hydrocarbon radicals and may lead to the discovery of other asymmetric radical reactions.
Genetic fusions favor tumorigenesis through degron loss in oncogenes
Authors: Liu Jing , Tokheim Collin , Lee Jonathan D. , Gan Wenjian , North Brian J. , Liu X. Shirley , Pandolfi Pier Paolo , Wei Wenyi
Published: November 2021

Chromosomal rearrangements can generate genetic fusions composed of two distinct gene sequences, many of which have been implicated in tumorigenesis and progression. Our study proposes a model whereby oncogenic gene fusions frequently alter the protein stability of the resulting fusion products, via exchanging protein degradation signal (degron) between gene sequences. Computational analyses of The Cancer Genome Atlas (TCGA) identify 2,406 cases of degron exchange events and reveal an enrichment of oncogene stabilization due to loss of degrons from fusion. Furthermore, we identify and experimentally validate that some recurrent fusions, such as BCR-ABL, CCDC6-RET and PML-RARA fusions, perturb protein stability by exchanging internal degrons. Likewise, we also validate that EGFR or RAF1 fusions can be stabilized by losing a computationally-predicted C-terminal degron. Thus, complementary to enhanced oncogene transcription via promoter swapping, our model of degron loss illustrates another general mechanism for recurrent fusion proteins in driving tumorigenesis.
Synchronized multi-wavelength soliton fiber laser via intracavity group delay modulation
Authors: Mao Dong , Wang Huaqiang , Zhang Heze , Zeng Chao , Du Yueqing , He Zhiwen , Sun Zhipei , Zhao Jianlin
Published: November 2021

Locking of longitudinal modes in laser cavities is the common path to generate ultrashort pulses. In traditional multi-wavelength mode-locked lasers, the group velocities rely on lasing wavelengths due to the chromatic dispersion, yielding multiple trains of independently evolved pulses. Here, we show that mode-locked solitons at different wavelengths can be synchronized inside the cavity by engineering the intracavity group delay with a programmable pulse shaper. Frequency-resolved measurements fully retrieve the fine temporal structure of pulses, validating the direct generation of synchronized ultrafast lasers from two to five wavelengths with sub-pulse repetition-rate up to ~1.26 THz. Simulation results well reproduce and interpret the key experimental phenomena, and indicate that the saturable absorption effect automatically synchronize multi-wavelength solitons in despite of the small residual group delay difference. These results demonstrate an effective approach to create synchronized complex-structure solitons, and offer an effective platform to study the evolution dynamics of nonlinear wavepackets.
Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage
Authors: Martín-Alonso Mara , Iqbal Sharif , Vornewald Pia M. , Lindholm Håvard T. , Damen Mirjam J. , Martínez Fernando , Hoel Sigrid , Díez-Sánchez Alberto , Altelaar Maarten , Katajisto Pekka , Arroyo Alicia G. , Oudhoff Menno J.
Published: November 2021

Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle cells may have. Here, we show that smooth muscle cells may be the dominant suppliers of BMP antagonists, which are niche factors essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the membrane-bound matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle cells, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we propose that MMP17 affects intestinal epithelial reprogramming after damage indirectly by cleaving diffusible factor(s) such as the matricellular protein PERIOSTIN. Together, we identify an important signaling axis that establishes a role for smooth muscle cells as modulators of intestinal epithelial regeneration and the intestinal stem cell niche.
Global predictions of primary soil salinization under changing climate in the 21st century
Authors: Hassani Amirhossein , Azapagic Adisa , Shokri Nima
Published: November 2021

Soil salinization has become one of the major environmental and socioeconomic issues globally and this is expected to be exacerbated further with projected climatic change. Determining how climate change influences the dynamics of naturally-occurring soil salinization has scarcely been addressed due to highly complex processes influencing salinization. This paper sets out to address this long-standing challenge by developing data-driven models capable of predicting primary (naturally-occurring) soil salinity and its variations in the world’s drylands up to the year 2100 under changing climate. Analysis of the future predictions made here identifies the dryland areas of South America, southern and western Australia, Mexico, southwest United States, and South Africa as the salinization hotspots. Conversely, we project a decrease in the soil salinity of the drylands in the northwest United States, the Horn of Africa, Eastern Europe, Turkmenistan, and west Kazakhstan in response to climate change over the same period.
A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin
Authors: Woodworth Joshua S. , Clemmensen Helena Strand , Battey Hannah , Dijkman Karin , Lindenstrøm Thomas , Laureano Raquel Salvador , Taplitz Randy , Morgan Jeffrey , Aagaard Claus , Rosenkrands Ida , Lindestam Arlehamn Cecilia S. , Andersen Peter , Mortensen Rasmus
Published: November 2021

Given the encouraging clinical results of both candidate subunit vaccines and revaccination with Bacillus Calmette-Guérin (BCG) against tuberculosis (TB), there is support for combining BCG and subunit vaccination for increased efficacy. BCG and Mycobacterium tuberculosis (Mtb) share ~98% of their genome and current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study is to design a TB subunit vaccine composed of antigens not shared with BCG and explore the advantages of this design in a BCG + subunit co-administration vaccine strategy. Eight protective antigens are selected to create an Mtb-specific subunit vaccine, named H107. Whereas traditional vaccines containing BCG-shared antigens exhibit in vivo cross-reactivity to BCG, H107 shows no cross-reactivity and does not inhibit BCG colonization. Instead, co-administering H107 with BCG leads to increased adaptive responses against both H107 and BCG. Importantly, rather than expanding BCG-primed T cells, H107 broadens the overall vaccine repertoire with new T cell clones and introduces ‘adjuvant-imprinted’ qualities including Th17 responses and less-differentiated Th1 cells. Collectively, these features of H107 are associated with a substantial increase in long-term protection.
Age-seroprevalence curves for the multi-strain structure of influenza A virus
Authors: Vinh Dao Nguyen , Nhat Nguyen Thi Duy , de Bruin Erwin , Vy Nguyen Ha Thao , Thao Tran Thi Nhu , Phuong Huynh Thi , Anh Pham Hong , Todd Stacy , Quan Tran Minh , Thanh Nguyen Thi Le , Lien Nguyen Thi Nam , Ha Nguyen Thi Hong , Hong Tran Thi Kim , Thai Pham Quang , Choisy Marc , Nguyen Tran Dang , Simmons Cameron P. , Thwaites Guy E. , Clapham Hannah E. , Chau Nguyen Van Vinh , Koopmans Marion , Boni Maciej F.
Published: November 2021

The relationship between age and seroprevalence can be used to estimate the annual attack rate of an infectious disease. For pathogens with multiple serologically distinct strains, there is a need to describe composite exposure to an antigenically variable group of pathogens. In this study, we assay 24,402 general-population serum samples, collected in Vietnam between 2009 to 2015, for antibodies to eleven human influenza A strains. We report that a principal components decomposition of antibody titer data gives the first principal component as an appropriate surrogate for seroprevalence; this results in annual attack rate estimates of 25.6% (95% CI: 24.1% – 27.1%) for subtype H3 and 16.0% (95% CI: 14.7% – 17.3%) for subtype H1. The remaining principal components separate the strains by serological similarity and associate birth cohorts with their particular influenza histories. Our work shows that dimensionality reduction can be used on human antibody profiles to construct an age-seroprevalence relationship for antigenically variable pathogens.