bluuebunny/crossref_metadata_2025 huggingface dataset:
University Students' Life Stressors and Mental Health in Georgia and German-Speaking Switzerland
Authors: Bachem Rahel , Makhashvili Nino , Maercker Andreas , Javakhishvili Jana Darejan , Aeschlimann Anaïs , Pilauri Ketevan , Latibashvili Tekla , Levin Yafit , Shengelia Natia
Published: March 2023

Abstract: Background: The university years are associated with a variety of stressors, and recently, COVID-19 has presented an additional burden on students’ mental well-being. As mental health manifestations of stressors may differ between countries, this study compared students from Switzerland and the Republic of Georgia regarding the burden of stressors and the role of potentially culture-dependent risk and protective factors of mental health (i.e., help-seeking, cross-cultural coping, fatalism, sense of coherence). Method: We assessed two samples of university students in Georgia ( N = 425) and German-speaking Switzerland ( N = 298), using a cross-sectional design. Quantitative data were collected with online questionnaires during the third wave of the pandemic. Mental health screenings included measures of depression, anxiety, and adjustment disorder. Results: General life- and COVID-19-related stress levels were higher in Georgia than in Switzerland. Georgian students experienced more adjustment disorder symptoms but lower levels of depression and anxiety. While Swiss students reported more protective factors (formal and informal help-seeking, sense of coherence), Georgian students experienced more risk factors (fatalism and avoidance coping). Despite significant correlations between potentially culture-dependent risk and protective factors and mental health, few associations remained significant above and beyond the impact of general life stress. Conclusions: The high prevalence of stressors and adjustment disorder symptoms and risk factors for mental health among Georgian students illustrates a potential need for psychosocial support with stress management. The cross-cultural applicability of Western models of student mental health services should be evaluated.
An Assessment of the Oceanic Physical and Biogeochemical Components of CMIP5 and CMIP6 Models for the Ross Sea Region
Authors: Rickard Graham J. , Behrens Erik , Bahamondes Dominguez Angela A. , Pinkerton Matt H.
Published: March 2023

The physical and biogeochemical performance of 16 CMIP5 and 16 CMIP6 Earth System models (ESM) are examined relative to present day (1976–2005) observational data sets for a Ross Sea Region (RSR) containing the Ross Gyre (RG) and the Ross Sea Continental Shelf. A relative ranking scheme using error metrics and published ESM properties (including climate sensitivity parameters and anomalous deep ocean convection statistics) enables identification of a “best” ensemble of models for the RSR. Over the RSR the CMIP6 models are generally found to have improved physical representations compared to the CMIP5 set (based on our metrics for sea ice concentration, sea surface temperature, salinity, and height, and mixed layer depth), but the CMIP5 and CMIP6 biogeochemical representations remain similar. Examination of mean properties for the period 2081 to 2100 for RCP8.5 and SSP585 for CMIP5 and CMIP6, respectively, shows significant surface temperature increases, with significant decreases in sea surface salinity, sea ice concentration, and mixed layer depth across the RSR. Biogeochemically, there are generally small increases in surface values for chlorophyll, integrated primary production, and zooplankton carbon concentrations. The projections also have robust reductions in surface nitrate, phosphate, and silicate across the RSR. For that part of the RG circulation to the east of 180°E—which we refer to as the “inner RG”—significant barotropic transport increases are found by the end of century.
The Representation of Sea Salt Aerosols and Their Role in Polar Climate Within CMIP6
Authors: Lapere Rémy , Thomas Jennie L. , Marelle Louis , Ekman Annica M. L. , Frey Markus M. , Lund Marianne Tronstad , Makkonen Risto , Ranjithkumar Ananth , Salter Matthew E. , Samset Bjørn Hallvard , Schulz Michael , Sogacheva Larisa , Yang Xin , Zieger Paul
Published: March 2023

Natural aerosols and their interactions with clouds remain an important uncertainty within climate models, especially at the poles. Here, we study the behavior of sea salt aerosols (SSaer) in the Arctic and Antarctic within 12 climate models from CMIP6. We investigate the driving factors that control SSaer abundances and show large differences based on the choice of the source function, and the representation of aerosol processes in the atmosphere. Close to the poles, the CMIP6 models do not match observed seasonal cycles of surface concentrations, likely due to the absence of wintertime SSaer sources such as blowing snow. Further away from the poles, simulated concentrations have the correct seasonality, but have a positive mean bias of up to one order of magnitude. SSaer optical depth is derived from the MODIS data and compared to modeled values, revealing good agreement, except for winter months. Better agreement for aerosol optical depth than surface concentration may indicate a need for improving the vertical distribution, the size distribution and/or hygroscopicity of modeled polar SSaer. Source functions used in CMIP6 emit very different numbers of small SSaer, potentially exacerbating cloud‐aerosol interaction uncertainties in these remote regions. For future climate scenarios SSP126 and SSP585, we show that SSaer concentrations increase at both poles at the end of the 21st century, with more than two times mid‐20th century values in the Arctic. The pre‐industrial climate CMIP6 experiments suggest there is a large uncertainty in the polar radiative budget due to SSaer.
Estimating Groundwater Recharge in Fully Integrated pde‐Based Hydrological Models
Authors: Waldowski Bastian , Sánchez‐León Emilio , Cirpka Olaf A. , Brandhorst Natascha , Hendricks Franssen Harrie‐Jan , Neuweiler Insa
Published: March 2023

Groundwater recharge is the main forcing of regional groundwater flow. In traditional partial‐differential‐equation (pde)‐based models that treat aquifers as separate compartments, groundwater recharge needs to be defined as a boundary condition or it is a coupling condition to other compartments. Integrated models that treat the vadose and phreatic zones as a continuum allow for a more sophisticated calculation of subsurface fluxes, as feedbacks between both zones are captured. However, they do not contain an explicit groundwater‐recharge term so it needs to be estimated by post‐processing. Groundwater recharge consists of changes in groundwater storage and of the flux crossing the water table, which can be calculated based on hydraulic gradients. We introduce a method to evaluate the change of groundwater storage by a time‐cumulative water balance over the depth section of water table fluctuations, avoiding the use of a specific yield. We demonstrate the approach first by a simple 1‐D vertical model that does not allow for lateral outflow and illustrates the ambiguity of computing groundwater recharge by different methods. We then apply the approach to a 3‐D model with a complex topography and subsurface structure. The latter example shows that groundwater recharge is highly variable in space and time with notable differences between regional and local estimates. Local heterogeneity of topography or subsurface properties results in complex redistribution patterns of groundwater. In fully integrated models, river‐groundwater exchange flow may severely bias the estimate of groundwater recharge. We, therefore, advise masking out groundwater recharge at river locations.
Large‐Domain Multisite Precipitation Generation: Operational Blueprint and Demonstration for 1,000 Sites
Authors: Papalexiou Simon Michael , Serinaldi Francesco , Clark Martyn P.
Published: March 2023

Stochastic simulations of spatiotemporal patterns of hydroclimatic processes, such as precipitation, are needed to build alternative but equally plausible inputs for water‐related design and management, and to estimate uncertainty and assess risks. However, while existing stochastic simulation methods are mature enough to deal with relatively small domains and coarse spatiotemporal scales, additional work is required to develop simulation tools for large‐domain analyses, which are more and more common in an increasingly interconnected world. This study proposes a methodological advancement in the CoSMoS framework, which is a flexible simulation framework preserving arbitrary marginal distributions and correlations, to dramatically decrease the computational burden and make the algorithm fast enough to perform large‐domain simulations in short time. The proposed approach focuses on correlated processes with mixed (zero‐inflated) Uniform marginal distributions. These correlated processes act as intermediates between the target process to simulate (precipitation) and parent Gaussian processes that are the core of the simulation algorithm. Working in the mixed‐Uniform space enables a substantial simplification of the so‐called correlation transformation functions, which represent a computational bottle neck in the original CoSMoS formulation. As a proof of concept, we simulate 40 years of daily precipitation records from 1,000 gauging stations in the Mississippi River basin. Moreover, we extend CoSMoS incorporating parent non‐Gaussian processes with different degrees of tail dependence and suggest potential improvements including the separate simulation of occurrence and intensity processes, and the use of advection, anisotropy, and nonstationary spatiotemporal correlation functions.
Paleogeographic Reconstruction of Precambrian Terranes Reworked by Phanerozoic Orogens: An Example Based on Detrital Zircon REE From Lhasa Terrane in Southern Tibet
Authors: Hu Pei‐yuan , Zhai Qing‐guo , Cawood Peter A. , Weinberg Roberto F. , Zhao Guo‐chun , Tang Yue , Liu Yi‐ming
Published: March 2023

Paleogeographic reconstruction of Precambrian terranes reworked by Phanerozoic orogens (e.g., the Tibetan Plateau) results in complex lithotectonic relations due to intracrustal reworking by tectonothermal events. Detrital zircon rare earth element (REE) databases at global (global major river sands) and regional (the Gangdese Mountains, southern Tibet) scales reveal trends in and Eu/Eu* that effectively record the crustal evolution of the source, including crustal thickness and redox state of the magma that generated the zircons. Regional comparisons of these chemical markers provide a new approach for paleogeographic reconstructions that we apply to study the origin of the Lhasa terrane, southern Tibet. Using Precambrian to early Paleozoic sedimentary and igneous rocks in the Lhasa terrane and compiling detrital zircon analyses from the northern margin of Gondwana, we show that the Lhasa terrane had an African affinity in the Rodinia–Gondwana supercontinent cycles (ca. 1.4–0.4 Ga).
Arbitrarily polarized bound states in the continuum with twisted photonic crystal slabs
Authors: Qin Haoye , Su Zengping , Liu Mengqi , Zeng Yixuan , Tang Man-Chung , Li Mengyao , Shi Yuzhi , Huang Wei , Qiu Cheng-Wei , Song Qinghua
Published: March 2023

Arbitrary polarized vortex beam induced by polarization singularity offers a new platform for both classical optics and quantum entanglement applications. Bound states in the continuum (BICs) have been demonstrated to be associated with topological charge and vortex polarization singularities in momentum space. For conventional symmetric photonic crystal slabs (PhCSs), BIC is enclosed by linearly polarized far fields with winding angle of 2π, which is unfavorable for high-capacity and multi-functionality integration-optics applications. Here, we show that by breaking σz-symmetry of the PhCS, asymmetry in upward and downward directions and arbitrarily polarized BIC can be realized with a bilayer-twisted PhCS. It exhibits elliptical polarization states with constant ellipticity angle at every point in momentum space within the vicinity of BIC. The topological nature of BIC reflects on the orientation angle of polarization state, with a topological charge of 1 for any value of ellipticity angle. Full coverage of Poincaré sphere (i.e., $$- {{\pi \over 4}} \le \chi \le {{\pi \over 4}}$$

−

π

4

≤
χ
≤

π

4

and $$- {{\pi \over 2}} \le \psi \le {{\pi \over 2}}$$

−

π

2

≤
ψ
≤

π

2

) and higher-order Poincaré sphere can be realized by tailoring the twist angles. Our findings may open up new avenues for applications in structured light, quantum optics, and twistronics for photons.
Deep clinical phenotyping of patients with obsessive-compulsive disorder: an approach towards detection of organic causes and first results
Authors: Runge Kimon , Reisert Marco , Feige Bernd , Nickel Kathrin , Urbach Horst , Venhoff Nils , Tzschach Andreas , Schiele Miriam A. , Hannibal Luciana , Prüss Harald , Domschke Katharina , Tebartz van Elst Ludger , Endres Dominique
Published: March 2023

In the revised diagnostic classification systems ICD-11 and DSM-5, secondary, organic forms of obsessive-compulsive disorder (OCD) are implemented as specific nosological entities. Therefore, the aim of this study was to clarify whether a comprehensive screening approach, such as the Freiburg-Diagnostic-Protocol for patients with OCD (FDP-OCD), is beneficial for detecting organic OCD forms. The FDP-OCD includes advanced laboratory tests, an expanded magnetic resonance imaging (MRI) protocol, and electroencephalography (EEG) investigations as well as automated MRI and EEG analyses. Cerebrospinal fluid (CSF), [18F]fluorodeoxyglucose positron emission tomography, and genetic analysis were added for patients with suspected organic OCD. The diagnostic findings of the first 61 consecutive OCD inpatients (32 female and 29 male; mean age: 32.7 ± 12.05 years) analyzed using our protocol were investigated. A probable organic cause was assumed in five patients (8%), which included three patients with autoimmune OCD (one patient with neurolupus and two with specific novel neuronal antibodies in CSF) and two patients with newly diagnosed genetic syndromes (both with matching MRI alterations). In another five patients (8%), possible organic OCD was detected (three autoimmune cases and two genetic cases). Immunological serum abnormalities were identified in the entire patient group, particularly with high rates of decreased “neurovitamin” levels (suboptimal vitamin D in 75% and folic acid in 21%) and increased streptococcal (in 46%) and antinuclear antibodies (ANAs; in 36%). In summary, the FDP-OCD screening led to the detection of probable or possible organic OCD forms in 16% of the patients with mostly autoimmune forms of OCD. The frequent presence of systemic autoantibodies such as ANAs further support the possible influence of autoimmune processes in subgroups of patients with OCD. Further research is needed to identify the prevalence of organic OCD forms and its treatment options.
Early-life stress biases responding to negative feedback and increases amygdala volume and vulnerability to later-life stress
Authors: Dutcher Ethan G. , Lopez-Cruz Laura , Pama E. A. Claudia , Lynall Mary-Ellen , Bevers Iris C. R. , Jones Jolyon A. , Khan Shahid , Sawiak Stephen J. , Milton Amy L. , Clatworthy Menna R. , Robbins Trevor W. , Bullmore Edward T. , Dalley Jeffrey W.
Published: March 2023

Early-life stress (ELS) or adversity, particularly in the form of childhood neglect and abuse, is associated with poor mental and physical health outcomes in adulthood. However, whether these relationships are mediated by the consequences of ELS itself or by other exposures that frequently co-occur with ELS is unclear. To address this question, we carried out a longitudinal study in rats to isolate the effects of ELS on regional brain volumes and behavioral phenotypes relevant to anxiety and depression. We used the repeated maternal separation (RMS) model of chronic ELS, and conducted behavioral measurements throughout adulthood, including of probabilistic reversal learning (PRL), responding on a progressive ratio task, sucrose preference, novelty preference, novelty reactivity, and putative anxiety-like behavior on the elevated plus maze. Our behavioral assessment was combined with magnetic resonance imaging (MRI) for quantitation of regional brain volumes at three time points: immediately following RMS, young adulthood without further stress, and late adulthood with further stress. We found that RMS caused long-lasting, sexually dimorphic biased responding to negative feedback on the PRL task. RMS also slowed response time on the PRL task, but without this directly impacting task performance. RMS animals were also uniquely sensitive to a second stressor, which disproportionately impaired their performance and slowed their responding on the PRL task. MRI at the time of the adult stress revealed a larger amygdala volume in RMS animals compared with controls. These behavioral and neurobiological effects persisted well into adulthood despite a lack of effects on conventional tests of ‘depression-like’ and ‘anxiety-like’ behavior, and a lack of any evidence of anhedonia. Our findings indicate that ELS has long-lasting cognitive and neurobehavioral effects that interact with stress in adulthood and may have relevance for understanding the etiology of anxiety and depression in humans.
Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes β-catenin palmitoylation to drive colorectal cancer progression
Authors: Zhang Qiang , Yang Xiaoya , Wu Jinjie , Ye Shubiao , Gong Junli , Cheng Wai Ming , Luo Zhanhao , Yu Jing , Liu Yugeng , Zeng Wanyi , Liu Chen , Xiong Zhizhong , Chen Yuan , He Zhen , Lan Ping
Published: March 2023

Metabolic reprogramming is a hallmark of cancer. However, it is not well known how metabolism affects cancer progression. We identified that metabolic enzyme acyl-CoA oxidase 1 (ACOX1) suppresses colorectal cancer (CRC) progression by regulating palmitic acid (PA) reprogramming. ACOX1 is highly downregulated in CRC, which predicts poor clinical outcome in CRC patients. Functionally, ACOX1 depletion promotes CRC cell proliferation in vitro and colorectal tumorigenesis in mouse models, whereas ACOX1 overexpression inhibits patient-derived xenograft growth. Mechanistically, DUSP14 dephosphorylates ACOX1 at serine 26, promoting its polyubiquitination and proteasomal degradation, thereby leading to an increase of the ACOX1 substrate PA. Accumulated PA promotes β-catenin cysteine 466 palmitoylation, which inhibits CK1- and GSK3-directed phosphorylation of β-catenin and subsequent β-Trcp-mediated proteasomal degradation. In return, stabilized β-catenin directly represses ACOX1 transcription and indirectly activates DUSP14 transcription by upregulating c-Myc, a typical target of β-catenin. Finally, we confirmed that the DUSP14-ACOX1-PA-β-catenin axis is dysregulated in clinical CRC samples. Together, these results identify ACOX1 as a tumor suppressor, the downregulation of which increases PA-mediated β-catenin palmitoylation and stabilization and hyperactivates β-catenin signaling thus promoting CRC progression. Particularly, targeting β-catenin palmitoylation by 2-bromopalmitate (2-BP) can efficiently inhibit β-catenin-dependent tumor growth in vivo, and pharmacological inhibition of DUSP14-ACOX1-β-catenin axis by Nu-7441 reduced the viability of CRC cells. Our results reveal an unexpected role of PA reprogramming induced by dephosphorylation of ACOX1 in activating β-catenin signaling and promoting cancer progression, and propose the inhibition of the dephosphorylation of ACOX1 by DUSP14 or β-catenin palmitoylation as a viable option for CRC treatment.
Self-folding soft-robotic chains with reconfigurable shapes and functionalities
Authors: Gu Hongri , Möckli Marino , Ehmke Claas , Kim Minsoo , Wieland Matthias , Moser Simon , Bechinger Clemens , Boehler Quentin , Nelson Bradley J.
Published: March 2023

Magnetic continuum soft robots can actively steer their tip under an external magnetic field, enabling them to effectively navigate in complex in vivo environments and perform minimally invasive interventions. However, the geometries and functionalities of these robotic tools are limited by the inner diameter of the supporting catheter as well as the natural orifices and access ports of the human body. Here, we present a class of magnetic soft-robotic chains (MaSoChains) that can self-fold into large assemblies with stable configurations using a combination of elastic and magnetic energies. By pushing and pulling the MaSoChain relative to its catheter sheath, repeated assembly and disassembly with programmable shapes and functions are achieved. MaSoChains are compatible with state-of-the-art magnetic navigation technologies and provide many desirable features and functions that are difficult to realize through existing surgical tools. This strategy can be further customized and implemented for a wide spectrum of tools for minimally invasive interventions.
Limitations of gene editing assessments in human preimplantation embryos
Authors: Liang Dan , Mikhalchenko Aleksei , Ma Hong , Marti Gutierrez Nuria , Chen Tailai , Lee Yeonmi , Park Sang-Wook , Tippner-Hedges Rebecca , Koski Amy , Darby Hayley , Li Ying , Van Dyken Crystal , Zhao Han , Wu Keliang , Zhang Jingye , Hou Zhenzhen , So Seongjun , Han Jongsuk , Park Jumi , Kim Chong-Jai , Zong Kai , Gong Jianhui , Yuan Yilin , Gu Ying , Shen Yue , Olson Susan B. , Yang Hui , Battaglia David , O’Leary Thomas , Krieg Sacha A. , Lee David M. , Wu Diana H. , Duell P. Barton , Kaul Sanjiv , Kim Jin-Soo , Heitner Stephen B. , Kang Eunju , Chen Zi-Jiang , Amato Paula , Mitalipov Shoukhrat
Published: March 2023

Range of DNA repair in response to double-strand breaks induced in human preimplantation embryos remains uncertain due to the complexity of analyzing single- or few-cell samples. Sequencing of such minute DNA input requires a whole genome amplification that can introduce artifacts, including coverage nonuniformity, amplification biases, and allelic dropouts at the target site. We show here that, on average, 26.6% of preexisting heterozygous loci in control single blastomere samples appear as homozygous after whole genome amplification indicative of allelic dropouts. To overcome these limitations, we validate on-target modifications seen in gene edited human embryos in embryonic stem cells. We show that, in addition to frequent indel mutations, biallelic double-strand breaks can also produce large deletions at the target site. Moreover, some embryonic stem cells show copy-neutral loss of heterozygosity at the cleavage site which is likely caused by interallelic gene conversion. However, the frequency of loss of heterozygosity in embryonic stem cells is lower than in blastomeres, suggesting that allelic dropouts is a common whole genome amplification outcome limiting genotyping accuracy in human preimplantation embryos.
Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251
Authors: Mattathil Jeffy G. , Volz Asisa , Onabajo Olusegun O. , Maynard Sean , Bixler Sandra L. , Shen Xiaoying X. , Vargas-Inchaustegui Diego , Robert-Guroff Marjorie , Lebranche Celia , Tomaras Georgia , Montefiori David , Sutter Gerd , Mattapallil Joseph J.
Published: March 2023

Human immunodeficiency virus (HIV) is a mucosally transmitted virus that causes immunodeficiency and AIDS. Developing efficacious vaccines to prevent infection is essential to control the epidemic. Protecting the vaginal and rectal mucosa, the primary routes of HIV entry has been a challenge given the significant compartmentalization between the mucosal and peripheral immune systems. We hypothesized that direct intranodal vaccination of mucosa associated lymphoid tissue (MALT) such as the readily accessible palatine tonsils could overcome this compartmentalization. Here we show that rhesus macaques primed with plasmid DNA encoding SIVmac251-env and gag genes followed by an intranodal tonsil MALT boost with MVA encoding the same genes protects from a repeated low dose intrarectal challenge with highly pathogenic SIVmac251; 43% (3/7) of vaccinated macaques remained uninfected after 9 challenges as compared to the unvaccinated control (0/6) animals. One vaccinated animal remained free of infection even after 22 challenges. Vaccination was associated with a ~2 log decrease in acute viremia that inversely correlated with anamnestic immune responses. Our results suggest that a combination of systemic and intranodal tonsil MALT vaccination could induce robust adaptive and innate immune responses leading to protection from mucosal infection with highly pathogenic HIV and rapidly control viral breakthroughs.
Transient dynamics of the phase transition in VO2 revealed by mega-electron-volt ultrafast electron diffraction
Authors: Xu Chenhang , Jin Cheng , Chen Zijing , Lu Qi , Cheng Yun , Zhang Bo , Qi Fengfeng , Chen Jiajun , Yin Xunqing , Wang Guohua , Xiang Dao , Qian Dong
Published: March 2023

Vanadium dioxide (VO2) exhibits an insulator-to-metal transition accompanied by a structural transition near room temperature. This transition can be triggered by an ultrafast laser pulse. Exotic transient states, such as a metallic state without structural transition, were also proposed. These unique characteristics let VO2 have great potential in thermal switchable devices and photonic applications. Although great efforts have been made, the atomic pathway during the photoinduced phase transition is still not clear. Here, we synthesize freestanding quasi-single-crystal VO2 films and examine their photoinduced structural phase transition with mega-electron-volt ultrafast electron diffraction. Leveraging the high signal-to-noise ratio and high temporal resolution, we observe that the disappearance of vanadium dimers and zigzag chains does not coincide with the transformation of crystal symmetry. After photoexcitation, the initial structure is strongly modified within 200 femtoseconds, resulting in a transient monoclinic structure without vanadium dimers and zigzag chains. Then, it continues to evolve to the final tetragonal structure in approximately 5 picoseconds. In addition, only one laser fluence threshold instead of two thresholds suggested in polycrystalline samples is observed in our quasi-single-crystal samples. Our findings provide essential information for a comprehensive understanding of the photoinduced ultrafast phase transition in VO2.
A Global Database of Soil Plant Available Phosphorus
Authors: McDowell R. W. , Noble A. , Pletnyakov P. , Haygarth P. M.
Published: March 2023

Soil phosphorus drives food production that is needed to feed a growing global population. However, knowledge of plant available phosphorus stocks at a global scale is poor but needed to better match phosphorus fertiliser supply to crop demand. We collated, checked, converted, and filtered a database of c. 575,000 soil samples to c. 33,000 soil samples of soil Olsen phosphorus concentrations. These data represent the most up-to-date repository of freely available data for plant available phosphorus at a global scale. We used these data to derive a model (R2 = 0.54) of topsoil Olsen phosphorus concentrations that when combined with data on bulk density predicted the distribution and global stock of soil Olsen phosphorus. We expect that these data can be used to not only show where plant available P should be boosted, but also where it can be drawn down to make more efficient use of fertiliser phosphorus and to minimise likely phosphorus loss and degradation of water quality.
WAVES – The Lucile Packard Children’s Hospital Pediatric Physiological Waveforms Dataset
Authors: Miller Daniel R. , Dhillon Gurpreet S. , Bambos Nicholas , Shin Andrew Y. , Scheinker David
Published: March 2023

WAVES is a large, single-center dataset comprising 9 years of high-frequency physiological waveform data from patients in intensive and acute care units at a large academic, pediatric medical center. The data comprise approximately 10.6 million hours of 1 to 20 concurrent waveforms over approximately 50,364 distinct patient encounters. The data have been de-identified, cleaned, and organized to facilitate research. Initial analyses demonstrate the potential of the data for clinical applications such as non-invasive blood pressure monitoring and methodological applications such as waveform-agnostic data imputation. WAVES is the largest pediatric-focused and second largest physiological waveform dataset available for research.
CD24-associated ceRNA network reveals prognostic biomarkers in breast carcinoma
Authors: Yu Bin , Zhao Ziyue , Chen Zhuoyuan , Xiang Cheng , Wang Pingxiao , Xiao Bo , Xia Yu , Li Aoyu , Xiao Tao , Li Hui
Published: March 2023

Breast cancer is one of the most common cancer types which is described as the leading cause of cancer death in women. After competitive endogenous RNA (ceRNA) hypothesis was proposed, this triple regulatory network has been observed in various cancers, and increasing evidences reveal that ceRNA network plays a significant role in the migration, invasion, proliferation of cancer cells. In the current study, our target is to construct a CD24-associated ceRNA network, and to further identify key prognostic biomarkers in breast cancer. Using the transcriptom profiles from TCGA database, we performed a comprehensive analysis between CD24high tumor samples and CD24low tumor samples, and identified 132 DElncRNAs, 602 DEmRNAs and 26 DEmiRNAs. Through comprehensive analysis, RP1-228H13.5/miR-135a-5p/BEND3 and SIM2 were identified as key CD24-associated biomarkers, which exhibited highly significance with overall survival, immune microenvironment as well as clinical features. To sum up the above, the current study constructed a CD24-associated ceRNA network, and RP1-228H13.5/miR-135a-5p/BEND3 and SIM2 axis worked as a potential therapeutic target and a predictor for BRCA diagnosis and prognosis.
Defining metabolic migraine with a distinct subgroup of patients with suboptimal inflammatory and metabolic markers
Authors: Gross Elena C. , Putananickal Niveditha , Orsini Anna-Lena , Schoenen Jean , Fischer Dirk , Soto-Mota Adrian
Published: March 2023

Emerging evidence suggest migraine is a response to cerebral energy deficiency or oxidative stress in the brain. Beta-hydroxybutyrate (BHB) is likely able to circumvent some of the meta-bolic abnormalities reported in migraine. Exogenous BHB was given to test this assumption and, in this post-hoc analysis, multiple metabolic biomarkers were identified to predict  clinical improvements. A randomized clinical trial, involving 41 patients with episodic migraine. Each treatment period was 12 weeks long, followed by eight weeks of washout phase / second run-in phase before entering the corresponding second treatment period. The primary endpoint was the number of migraine days in the last 4 weeks of treatment adjusted for baseline. BHB re-sponders were identified (those with at least a 3-day reduction in migraine days over placebo) and its predictors were evaluated using Akaike’s Information Criterion (AIC) stepwise boot-strapped analysis and logistic regression. Responder analysis showed that metabolic markers could identify a “metabolic migraine” subgroup, which responded to BHB with a 5.7 migraine days reduction compared to the placebo. This analysis provides further support for a “metabolic migraine” subtype. Additionally, these analyses identified low-cost and easily accessible biomarkers that could guide recruitment in future research on this subgroup of patients.

This study is part of the trial registration: ClinicalTrials.gov: NCT03132233, registered on 27.04.2017, https://clinicaltrials.gov/ct2/show/NCT03132233
Associations of body size with all-cause and cause-specific mortality in healthy older adults
Authors: Carr Prudence R. , Webb Katherine L. , Neumann Johannes T. , Thao Le T. P. , Beilin Lawrence J. , Ernst Michael E. , Fitzgibbon Bernadette , Gasevic Danijela , Nelson Mark R. , Newman Anne B. , Orchard Suzanne G. , Owen Alice , Reid Christopher M. , Stocks Nigel P. , Tonkin Andrew M. , Woods Robyn L. , McNeil John J.
Published: March 2023

In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0–29.9 kg/m2 [HR25-29.9 vs 21–24.9 kg/m2: 0.85; 95% CI, 0.73–1.00] while the highest risk was in those who were underweight [HRBMI <21 kg/m2 vs BMI 21–24.9 kg/m2: 1.82; 95% CI 1.30–2.55], leading to a clear U-shaped relationship. In women, all-cause mortality was highest in those with the lowest BMI leading to a J-shaped relationship (HRBMI <21 kg/m2 vs BMI 21–24.9 kg/m2: 1.64; 95% CI 1.26–2.14). Waist circumference showed a weaker relationship with all-cause mortality in both men and women. There was little evidence of a relationship between either index of body size and subsequent cancer mortality in men or women, while non-cardiovascular non-cancer mortality was higher in underweight participants. For older men, being overweight was found to be associated with a lower risk of all-cause mortality, while among both men and women, a BMI in the underweight category was associated with a higher risk. Waist circumference alone had little association with all-cause or cause-specific mortality risk.

Trial registration ASPREE https://ClinicalTrials.gov number NCT01038583.
Examining behavioural test sensitivity and locomotor proxies of anxiety-like behaviour in zebrafish
Authors: Johnson Andréa , Loh Erica , Verbitsky Ryan , Slessor Jordan , Franczak Brian C. , Schalomon Melike , Hamilton Trevor J.
Published: March 2023

This study assessed the sensitivity of four anxiety-like behaviour paradigms in zebrafish: the novel tank dive test, shoaling test, light/dark test, and the less common shoal with novel object test. A second goal was to measure the extent to which the main effect measures are related to locomotor behaviours to determine whether swimming velocity and freezing (immobility) are indicative of anxiety-like behaviour. Using the well-established anxiolytic, chlordiazepoxide, we found the novel tank dive to be most sensitive followed by the shoaling test. The light/dark test and shoaling plus novel object test were the least sensitive. A principal component analysis and a correlational analysis also showed the locomotor variables, velocity and immobility, did not predict the anxiety-like behaviours across all behaviour tests.
Verteporfin-induced proteotoxicity impairs cell homeostasis and survival in neuroblastoma subtypes independent of YAP/TAZ expression
Authors: Condurat Alexandra-Larisa , Aminzadeh-Gohari Sepideh , Malnar Mirjana , Schider Nicole , Opitz Leonie , Thomas Ria , Menon Vishal , Kofler Barbara , Pruszak Jan
Published: March 2023

Neuroblastoma (NB) is a highly aggressive extracranial solid tumor in children. Due to its heterogeneity, NB remains a therapeutic challenge. Several oncogenic factors, including the Hippo effectors YAP/TAZ, are associated with NB tumorigenesis. Verteporfin (VPF) is an FDA-approved drug shown to directly inhibit YAP/TAZ activity. Our study aimed to investigate VPF’s potential as a therapeutic agent in NB. We show that VPF selectively and efficiently impairs the viability of YAP/TAZ-expressing NB GI-ME-N and SK-N-AS cells, but not of non-malignant fibroblasts. To investigate whether VPF-mediated NB cell killing is YAP-dependent, we tested VPF potency in CRISPR-mediated YAP/TAZ knock-out GI-ME-N cells, and BE(2)-M17 NB cells (a MYCN-amplified, predominantly YAP-negative NB subtype). Our data shows that VPF-mediated NB cell killing is not dependent on YAP expression. Moreover, we determined that the formation of higher molecular weight (HMW) complexes is an early and shared VPF-induced cytotoxic mechanism in both YAP-positive and YAP-negative NB models. The accumulation of HMW complexes, involving STAT3, GM130 and COX IV proteins, impaired cell homeostasis and triggered cell stress and cell death mechanisms. Altogether, our study shows significant in vitro and in vivo VPF-induced suppression of NB growth, making VPF a potential therapeutic candidate against NB.
Enhanced performance of flexible quantum dot light-emitting diodes using a low-temperature processed PTAA hole transport layer
Authors: Ha Hyoun Ji , Kim Min Gye , Ma Jin Hyun , Jeong Jun Hyung , Park Min Ho , Kang Seong Jae , Kim Wonsik , Park Soohyung , Kang Seong Jun
Published: March 2023

Low-temperature processing is important for improving the stability and performance of flexible quantum dot light-emitting diodes (QLEDs). In this study, QLEDs were fabricated using poly[bis(4-phenyl) (2,4,6-trimethylphenyl)amine] (PTAA) as a suitable hole transport layer (HTL) material owing to its low-temperature processability and vanadium oxide as the low-temperature solution-processable hole injection layer material. The maximum luminance and highest current efficiency of the QLEDs on a glass substrate with an optimal PTAA HTL was 8.9 × 104 Cd/m2 and 15.9 Cd/A, respectively, which was comparable to that of conventional devices. The QLEDs on a flexible substrate showed a maximum luminance of 5.4 × 104 Cd/m2 and highest current efficiency of 5.1 Cd/A. X-ray and ultraviolet photoelectron spectroscopies were used to investigate the chemical state and interfacial electronic structure according to the materials and the state changes of the HTL, respectively. The interfacial electronic structure showed that PTAA exhibited a better hole transport ability owing to its low hole injection barrier ($${\Phi }_{{\text{h}}}$$

Φ
h

). Moreover, QLEDs with a PTAA HTL could operate as photosensors under reverse bias conditions. These results indicate that the low-temperature-processed PTAA HTL is suitable for improving the performance of flexible QLEDs.
A high throughput method for egg size measurement in Drosophila
Authors: Barghi Neda , Ramirez-Lanzas Claudia
Published: March 2023

Life-history traits are used as proxies of fitness in insects including Drosophila. Egg size is an adaptive and ecologically important trait potentially with genetic variation across different populations. However, the low throughput of manual measurement of egg size has hampered the widespread use of this trait in evolutionary biology and population genetics. We established a method for accurate and high throughput measurement of Drosophila egg size using large particle flow cytometry (LPFC). The size estimates using LPFC are accurate and highly correlated with the manual measurements. The measurement of egg size is high throughput (average of 214 eggs measured per minute) and viable eggs of a specific size can be sorted rapidly (average of 70 eggs per minute). Sorting by LPFC does not reduce the survival of eggs making it a suitable approach for sorting eggs for downstream analyses. This protocol can be applied to any organism within the detectable size range (10–1500 µm) of the large particle flow cytometers. We discuss the potential applications of this method and provide recommendations for optimizing the protocol for other organisms.
A transparent artificial intelligence framework to assess lung disease in pulmonary hypertension
Authors: Mamalakis Michail , Dwivedi Krit , Sharkey Michael , Alabed Samer , Kiely David , Swift Andrew J.
Published: March 2023

Recent studies have recognized the importance of characterizing the extent of lung disease in pulmonary hypertension patients by using Computed Tomography. The trustworthiness of an artificial intelligence system is linked with the depth of the evaluation in functional, operational, usability, safety and validation dimensions. The safety and validation of an artificial tool is linked to the uncertainty estimation of the model’s prediction. On the other hand, the functionality, operation and usability can be achieved by explainable deep learning approaches which can verify the learning patterns and use of the network from a generalized point of view. We developed an artificial intelligence framework to map the 3D anatomical models of patients with lung disease in pulmonary hypertension. To verify the trustworthiness of the framework we studied the uncertainty estimation of the network’s prediction, and we explained the learning patterns of the network. Therefore, a new generalized technique combining local explainable and interpretable dimensionality reduction approaches (PCA-GradCam, PCA-Shape) was developed. Our open-source software framework was evaluated in unbiased validation datasets achieving accurate, robust and generalized results.
Serum metabolomic profile of hair dye use
Authors: Lim Jung-eun , Huang Jiaqi , Weinstein Stephanie J. , Parisi Dominick , Mӓnnistö Satu , Albanes Demetrius
Published: March 2023

The International Agency for Research on Cancer reported that some chemicals in hair dyes are probably carcinogenic to those exposed to them occupationally. Biological mechanisms through which hair dye use may be related to human metabolism and cancer risk are not well-established. We conducted the first serum metabolomic examination comparing hair dye users and nonusers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Metabolite assays were conducted using ultrahigh performance liquid chromatography-tandem mass spectrometry. The association between metabolite levels and hair dye use was estimated using linear regression, adjusting for age, body mass index, smoking, and multiple comparisons. Among the 1,401 detected metabolites, 11 compounds differed significantly between the two groups, including four amino acids and three xenobiotics. Redox-related glutathione metabolism was heavily represented, with L-cysteinylglycine disulfide showing the strongest association with hair dye (effect size (β) =  −  0.263; FDR adjusted p-value = 0.0311), along with cysteineglutathione disulfide (β =  − 0.685; FDR adjusted p-value = 0.0312). 5alpha-Androstan-3alpha,17beta-diol disulfate was reduced in hair dye users (β =  − 0.492; FDR adjusted p-value = 0.077). Several compounds related to antioxidation/ROS and other pathways differed significantly between hair dye users and nonusers, including metabolites previously associated with prostate cancer. Our findings suggest possible biological mechanisms through which the use of hair dye could be associated with human metabolism and cancer risk.
Controllable large positive and negative Goos–Hänchen shifts with a double-Lambda atomic system
Authors: Othman Anas , Asiri Saeed , Al-Amri M.
Published: March 2023

We study the Goos–Hänchen shift (GHS) of a reflected light beam from a cavity containing a double-$$\Lambda$$
Λ
atomic medium that is bounded by two glass slabs. Applying both coherent and incoherent fields to the atomic medium leads to positive and negative controllability of GHS. For some specific values of the parameters of the system, the amplitude of the GHS becomes large, namely, in the order of $$\sim 10^{3}$$

∼

10
3

times the wavelength of the incident light beam. These large shifts are found at more than one angle of incidence with a wide range of parameters of the atomic medium.
The role of scarcity promotion and cause-related events in impulse purchase in the agricultural product live stream
Authors: Li Xiaolin , Guo Mengqian , Huang Dunhu
Published: March 2023

Harvest agricultural products are perishable. If they cannot be sold, there will be serious grain loss and food waste. It is an important issue related to human sustainable development and urgent to address. As the most popular way of shopping, live shopping has achieved remarkable achievements, while the existing research is relatively silent on how to promote the sales of agricultural products in the context of live streams. Based on S–O–R theory and dual-system theory, three studies investigated the intrinsic mechanism of consumers’ impulse purchase intention (IPI) in live streams. The results show that scarcity promotion (SP) and cause-related events (CRE) are positively correlated with consumers’ IPI through arousal and moral elevation. Interestingly, when SP and CRE are presented at the same time, the impact of CRE on IPI is no longer significant. Overall, the proposed model could be used to predict consumers’ willingness and provide the choice of marketing strategy to promote the sale of agricultural products, which has significant theoretical and practical value.
Stent expansion evaluated by optical coherence tomography and subsequent outcomes
Authors: Lee Bom , Baraki Teklay Gebrehaweria , Kim Byung Gyu , Lee Yong-Joon , Lee Seung-Jun , Hong Sung-Jin , Ahn Chul-Min , Shin Dong-Ho , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo , Kim Jung-Sun
Published: March 2023

Regarding stent expansion indices, previous optical coherence tomography (OCT) studies have shown minimal stent area (MSA) to be most predictive of adverse events. We sought to evaluate the impact of various stent expansion and apposition indices by post-stent OCT on clinical outcomes and find OCT-defined optimal stent implantation criteria. A total of 1071 patients with 1123 native coronary artery lesions treated with new-generation drug-eluting stents with OCT guidance and final post-stent OCT analysis were included. Several stent expansion indices (MSA, MSA/average reference lumen area, MSA/distal reference lumen area, mean stent expansion, and stent expansion by linear model [stent volume/adaptive reference lumen volume]) were evaluated for their association with device-oriented clinical endpoints (DoCE) including cardiac death, target vessel-related myocardial infarction (MI) or stent thrombosis, and target lesion revascularization. MSA was negatively correlated with the risk of DoCE (hazard ratio [HR] 0.80 [0.68‒0.94]). However, stent expansion by linear model representing the overall volumetric stent expansion was associated with greater risk of DoCE (HR 1.02 [1.00‒1.04]). As categorical criteria, MSA < 5.0 mm2 (HR 3.90 [1.99‒7.65]), MSA/distal reference lumen area < 90% (HR 2.16 [1.12‒4.19]), and stent expansion by linear model ≥ 65.0% (HR 1.95 [1.03‒3.89]) were independently associated with DoCE. This OCT study highlights the importance of sufficient stent expansion to achieve adequate, absolute, and relative MSA criteria for improving clinical outcome. It also emphasises that overall volumetric excessive stent expansion may have detrimental effects.