bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual and ocular findings in children with fetal alcohol spectrum disorders (FASD): validating the FASD Eye Code in a clinical setting
Authors: Ayoub Lucyn , Aring Eva , Gyllencreutz Emelie , Landgren Valdemar , Svensson Leif , Landgren Magnus , Grönlund Marita Andersson 
Published: March 2023

ObjectiveFetal alcohol spectrum disorders (FASD) is an umbrella term covering a spectrum of medical conditions caused by prenatal alcohol exposure. The FASD Eye Code is a new complementary ophthalmological diagnostic tool created to corroborate the complex FASD diagnosis. The aim of this work was to validate the FASD Eye Code by testing it on a second group of children diagnosed with FASD in a clinical setting.Methods and analysisA clinical study was carried out in a group of 21 children (13 males, 8 females, mean age 13.3 years) investigated for suspected FASD and a healthy sex-matched and age-matched control group (n=21). The participants underwent a detailed ophthalmological examination including visual perception problems (VPPs) assessment. Clinical examination results were compiled, and total scores were calculated according to the FASD Eye Code protocol (range 4–16).ResultsThe median total score in the FASD group was 8. Eight individuals in the FASD group and none of the controls obtained a total score of ≥9 corresponding to 38% sensitivity and 100% specificity with an area under the curve of 0.90. A cut-off total score of ≥8 showed 52% sensitivity and 95% specificity. One individual in the FASD group versus 12 controls had a total score of 4, representing normal findings. No significant difference between the two groups regarding VPPs was seen.ConclusionThe FASD Eye Code can be used as a complementary diagnostic tool for FASD to assist in diagnosis and to detect ophthalmological abnormalities in individuals with suspected FASD.
A cross-sectional study of anxiety and depression caseness in female competitive figure skaters in Sweden
Authors: Jederström Moa , Agnafors Sara , Ekegren Christina L , Fagher Kristina , Gauffin Håkan , Korhonen Laura , Park Jennifer , Spreco Armin , Timpka Toomas 
Published: March 2023

ObjectivesLittle is known about figure skaters’ mental health. This study aimed to describe anxiety and depression caseness (defined as a screening condition qualifying for psychiatric examination) in competitive figure skaters and analyse factors associated with such caseness.MethodsA cross-sectional study was performed in April 2019 among all competitive figure skaters in the south-eastern region of Sweden (N=400). The primary outcomes were anxiety caseness, measured using the short-form Spielberger State-Trait Anxiety Inventory and depression caseness, measured using the WHO-5 index. Multivariable logistic regression models were employed to determine the association between anxiety caseness and explanatory factors.ResultsIn total, 36% (n=142) of the invited skaters participated. Only females (n=137), mean age 12.9 (SD 3.0) years) were selected for analysis. Of the participating skaters, 47% displayed anxiety caseness and 10% depression caseness. Overweight body image perception (OR 5.9; 95% CI 2.0 to 17.6; p=0.001) and older age (OR 1.2; 95% CI 1.1 to 1.4; p=0.005) were associated with anxiety caseness. Skaters reporting no caseness were younger than those reporting only anxiety caseness (mean age difference −1.9 years; 95% CI −3.1 to −0.7; p=0.001) or anxiety and depression caseness (OR −3.5 years; 95% CI −5.6 to −1.5 years; p<0.001).ConclusionAnxiety caseness was associated with overweight body image perception and older age in female competitive figure skaters. Older skaters reported generally worse mental health. More research on the mental health of figure skaters is warranted, considering comorbidity and focusing on those needing further assessment and support.
Reproductive and sexual health of Australian adolescents exposed to family and domestic violence
Authors: Orr Carol , Kelty Erin , O'Donnell Melissa , Fisher Colleen M , Glauert Rebecca , Preen David B 
Published: March 2023

BackgroundThere is a dearth of research investigating sexually transmitted infections (STIs) in children exposed to family and domestic violence (FDV). Further, there is no research on terminations of pregnancy in children exposed to FDV.MethodsThis retrospective cohort study used linked administrative data from Western Australia to investigate whether exposure to FDV is associated with a risk of hospitalisations for STIs and terminations of pregnancy in adolescents. This study involved children born from 1987 to 2010 whose mother was a victim of FDV. Identification of family and domestic violence was from two sources: police and hospital records. This approach provided an exposed cohort of 16 356 and a non-exposed cohort of 41 996. Dependant variables were hospitalisations for pregnancy terminations and STIs in children aged from 13 up to 18 years of age. The primary explanatory variable was exposure to FDV. Multivariable Cox regression was used to investigate the association of FDV exposure and the outcomes.ResultsFollowing adjustment for sociodemographic and clinical factors, children exposed to FDV had an increased risk of hospitalisations for STIs (HR 1.49, 95% CI 1.15 to 1.92) and terminations of pregnancy (HR 1.34, 95% CI 1.09 to 1.63) as an adolescent than non-exposed peers.ConclusionChildren exposed to FDV are at an increased risk of hospitalisation for STI and termination of pregnancy as an adolescent. Effective interventions are needed to support children exposed to FDV.
Risk of COVID-19 among unvaccinated and vaccinated patients with systemic lupus erythematosus: a general population study
Authors: Jiang Xiaofeng , Sparks Jeffrey , Wallace Zachary , Deng Xinjia , Li Hui , Lu Na , Xie Dongxing , Wang Yilun , Zeng Chao , Lei Guanghua , Wei Jie , Zhang Yuqing 
Published: March 2023

ObjectiveTo compare the risk of SARS-CoV-2 infection and its related severe sequelae between patients with systemic lupus erythematosus (SLE) and the general population according to COVID-19 vaccination status.MethodsWe performed cohort studies using data from The Health Improvement Network to compare the risks of SARS-CoV-2 infection and severe sequelae between patients with SLE and the general population. Individuals aged 18–90 years with no previously documented SARS-CoV-2 infection were included. We estimated the incidence rates and HRs of SARS-CoV-2 infection and severe sequelae between patients with SLE and the general population according to COVID-19 vaccination status using exposure score overlap weighted Cox proportional hazards model.ResultsWe identified 3245 patients with SLE and 1 755 034 non-SLE individuals from the unvaccinated cohort. The rates of SARS-CoV-2 infection, COVID-19 hospitalisation, COVID-19 death and combined severe outcomes per 1000 person-months were 10.95, 3.21, 1.16 and 3.86 among patients with SLE, and 8.50, 1.77, 0.53 and 2.18 among general population, respectively. The corresponding adjusted HRs were 1.28 (95% CI: 1.03 to 1.59), 1.82 (95% CI: 1.21 to 2.74), 2.16 (95% CI: 1.00 to 4.79) and 1.78 (95% CI: 1.21 to 2.61). However, no statistically significant differences were observed between vaccinated patients with SLE and vaccinated general population over 9 months of follow-up.ConclusionWhile unvaccinated patients with SLE were at higher risk of SARS-CoV-2 infection and its severe sequelae than the general population, no such difference was observed among vaccinated population. The findings indicate that COVID-19 vaccination provides an adequate protection to most patients with SLE from COVID-19 breakthrough infection and its severe sequelae.
Do isotropic tidal forces imply isotropic cosmic expansion?
Authors: Dias Fabio Scalco , Gomes Leandro Gustavo , Mello Luis Fernando 
Published: March 2023

AbstractWe investigate the dynamics of the spatially flat universes submitted to isotropic tidal forces and adiabatic expansion under Einstein’s equations. Surprisingly, the tendency to a high Hubble anisotropy at late times starts to appear as far as we assume a strong-like energy condition to hold, a characteristic which becomes dominant in the radiation era and even more stringent under a stiff matter regime. This is a rather counter-intuitive behavior that shows us how, from the conceptual viewpoint, the Hubble parameter tends to anisotropize even when the universe is dominated by isotropic gravitational forces and usual physical conditions. We introduce the parameterb, which measures the relative variation in the magnitudes of the Hubble anisotropy against the scale factor, to show that mechanisms violating such an energy condition can compensate for this anisotropy increase. We also discuss if there is theoretical support for the existence of observational Hubble anisotropy in the late-time universe.
The hubble rate trouble: an effective field theory of dark matter
Authors: Jesus Alvaro S. de , Pinto-Neto Nelson , Queiroz Farinaldo S. , Silk Joseph , Silva Dêivid R. da 
Published: March 2023

AbstractThe Hubble constant inferred from the 6-parameter fit to the CMB power spectrum conflicts with the value obtained from direct measurements via type Ia supernova and Cepheids observations. We write down effective operators involving spin-0, spin-1/2, and spin-1 dark matter that lead to the relativistic production of dark matter particles at early times, and consequently lead to an increase in the number of relativistic degrees of freedom. This mechanism which is amenable to CMB, BBN, and structure formation observables can sufficiently raise the value of the Hubble constant derived from CMB and reconcile local and CMB probes of the Hubble constant. This mechanism alone increases $$H_0$$

H
0

up to $$70\, \textrm{km}\, \textrm{s}^{-1} \, \textrm{Mpc}^{-1}$$

70

km

s

-
1

Mpc

-
1

, and with the help of a Phantom-like cosmology, reach $$H_0 \simeq $$

H
0

≃

71–73 $$\textrm{km} \,\textrm{s}^{-1} \textrm{Mpc}^{-1}$$

km

s

-
1

Mpc

-
1

. Lastly, we outline the region of parameter space which reproduces $$H_0 \simeq $$

H
0

≃

71–73 $$\textrm{km} \,\textrm{s}^{-1} \, \textrm{Mpc}^{-1}$$

km

s

-
1

Mpc

-
1

while obeying all relevant constraints.
p38MAPKα Stromal Reprogramming Sensitizes Metastatic Breast Cancer to Immunotherapy
Authors: Faget Douglas V. , Luo Xianmin , Inkman Matthew J. , Ren Qihao , Su Xinming , Ding Kai , Waters Michael R. , Raut Ganesh Kumar , Pandey Gaurav , Dodhiawala Paarth B. , Ramalho-Oliveira Renata , Ye Jiayu , Cole Thomas , Murali Bhavna , Zheleznyak Alexander , Shokeen Monica , Weiss Kurt R. , Monahan Joseph B. , DeSelm Carl J. , Lee Adrian V. , Oesterreich Steffi , Weilbaecher Katherine N. , Zhang Jin , DeNardo David G. , Stewart Sheila A. 
Published: March 2023

Abstract

Metastatic breast cancer is an intractable disease that responds poorly to immunotherapy. We show that p38MAPKα inhibition (p38i) limits tumor growth by reprogramming the metastatic tumor microenvironment in a CD4+ T cell-, IFNγ-, and macrophage-dependent manner. To identify targets that further increased p38i efficacy, we utilized a stromal labeling approach and single-cell RNA sequencing. Thus, we combined p38i and an OX40 agonist that synergistically reduced metastatic growth and increased overall survival. Intriguingly, patients with a p38i metastatic stromal signature had better overall survival that was further improved by the presence of an increased mutational load, leading us to ask if our approach would be effective in antigenic breast cancer. The combination of p38i, anti-OX40, and cytotoxic T-cell engagement cured mice of metastatic disease and produced long-term immunologic memory. Our findings demonstrate that a detailed understanding of the stromal compartment can be used to design effective antimetastatic therapies.

Significance:
Immunotherapy is rarely effective in breast cancer. We dissected the metastatic tumor stroma, which revealed a novel therapeutic approach that targets the stromal p38MAPK pathway and creates an opportunity to unleash an immunologic response. Our work underscores the importance of understanding the tumor stromal compartment in therapeutic design.
This article is highlighted in the In This Issue feature, p. 1275
Digital Spatial Profiling Links Beta-2-microglobulin Expression with Immune Checkpoint Blockade Outcomes in Head and Neck Squamous Cell Carcinoma
Authors: Gavrielatou Niki , Vathiotis Ioannis , Aung Thazin Nwe , Shafi Saba , Burela Sneha , Fernandez Aileen I. , Moutafi Myrto , Burtness Barbara , Economopoulou Panagiota , Anastasiou Maria , Foukas Periklis , Psyrri Amanda , Rimm David L. 
Published: March 2023

Programmed cell death protein-1 (PD-1)-targeted immunotherapy is approved for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treatment. Although its efficacy correlates with PD-L1 expression, response is limited even among positive cases. We employed digital spatial profiling (DSP) to discover potential biomarkers of immunotherapy outcomes in HNSCC. Fifty prospectively collected, pretreatment biopsy samples from patients with anti-PD-1–treated R/M HNSCC, were assessed using DSP, for 71 proteins in four molecularly defined compartments (tumor, leukocyte, macrophage, and stroma). Markers were evaluated for associations with progression-free (PFS) and overall survival (OS). High beta-2 microglobulin (B2M), LAG-3, CD25, and 4-1BB in tumor; high B2M, CD45, CD4 in stroma, and low fibronectin in the macrophage compartment, correlated with prolonged PFS. Improved PFS and OS were observed for cases with high B2M by quantitative and mRNA. Findings were validated in an independent cohort for PFS (HR, 0.41; 95% confidence interval, 0.19–0.93; P = 0.034). B2M-high tumors showed enrichment with immune cell and immune checkpoint markers. Our study illustrates B2M expression is associated with improved survival for immune checkpoint inhibitor (ICI)-treated HNSCC.Significance:In the current study, DSP revealed the positive association of B2M expression in the tumor compartment with immunotherapy outcomes in R/M HNSCC.
Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy
Authors: Subramaniam Gunasekaran , Schleicher Katharina , Kovanich Duangnapa , Zerio Anna , Folkmanaite Milda , Chao Ying-Chi , Surdo Nicoletta C. , Koschinski Andreas , Hu Jianshu , Scholten Arjen , Heck Albert J.R. , Ercu Maria , Sholokh Anastasiia , Park Kyung Chan , Klussmann Enno , Meraviglia Viviana , Bellin Milena , Zanivan Sara , Hester Svenja , Mohammed Shabaz , Zaccolo Manuela 
Published: March 2023

Background:
Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac β-adrenergic signaling has served as the prototypical system to elucidate cAMP compartmentalization. Although studies in cardiac myocytes have provided an understanding of the location and properties of a handful of cAMP subcellular compartments, an overall view of the cellular landscape of cAMP nanodomains is missing.

Methods:
Here, we combined an integrated phosphoproteomics approach that takes advantage of the unique role that individual PDEs play in the control of local cAMP, with network analysis to identify previously unrecognized cAMP nanodomains associated with β-adrenergic stimulation. We then validated the composition and function of one of these nanodomains using biochemical, pharmacological, and genetic approaches and cardiac myocytes from both rodents and humans.

Results:
We demonstrate the validity of the integrated phosphoproteomic strategy to pinpoint the location and provide critical cues to determine the function of previously unknown cAMP nanodomains. We characterize in detail one such compartment and demonstrate that the PDE3A2 isoform operates in a nuclear nanodomain that involves SMAD4 (SMAD family member 4) and HDAC-1 (histone deacetylase 1). Inhibition of PDE3 results in increased HDAC-1 phosphorylation, leading to inhibition of its deacetylase activity, derepression of gene transcription, and cardiac myocyte hypertrophic growth.

Conclusions:
We developed a strategy for detailed mapping of subcellular PDE-specific cAMP nanodomains. Our findings reveal a mechanism that explains the negative long-term clinical outcome observed in patients with heart failure treated with PDE3 inhibitors.
A Translation of Jaun Elia’s Preface of Shāyad
Authors: Iqbal Hamza 
Published: March 2023

Abstract
Arguably the most “popular” Hindi-Urdu poet today, Jaun Elia involuntarily migrated from his hometown of Amroha in 1957 and soon after started his literary and intellectual activities in the foreign sprawling landscape of Karachi. He served as an editor and publisher of a literary journal titled Inshā’, produced scholarly works, and translated important philosophical and theological texts from Arabic and Persian into Urdu. But Jaun’s most sincere investment remained towards the craft of poetry, particularly to the ghazal, which he wrote prolifically and recited routinely at local and international mushāʿarahs till his death in 2002.
The dibāchah (prologue-essay) from his first poetry collection, Shāyad, that was published only when Jaun was approaching sixty, is a formidable—even if at times formally complex—example of modern Urdu prose. This translation of the prologue-essay is not only intended to introduce Jaun’s philosophical, ideological, and aesthetical influences to the broader English-speaking publics but also to provide an aperture to those symbolic flashes from the poet’s biography which he wished to share with his readers.
Climatology of Low-Level Clouds over Western Equatorial Africa Based on Ground Observations and Satellites
Authors: Champagne O. , Aellig R. , Fink A. H. , Philippon N. , Camberlin P. , Moron V. , Knippertz P. , Seze G. , van der Linden R. 
Published: March 2023

Abstract
The tropical cloud forest ecosystem in western equatorial Africa (WEA) is known to be sensitive to the presence of an extensive and persistent low-level stratiform cloud deck during the long dry season from June to September (JJAS). Here, we present a new climatology of the diurnal cycle of the low-level cloud cover from surface synoptic stations over WEA during JJAS 1971–2019. For the period JJAS 2008–19, we also utilized estimates of cloudiness from four satellite products, namely, the Satellite Application Facility on Support to Nowcasting and Very Short Range Forecasting (SAFNWC) cloud classification, the Day and Night Microphysical Schemes (DMS/NMS), and cross sections from CALIPSO and CloudSat (2B-GEOPROF-lidar). A comparison with surface stations reveals that the NMS at night together with SAFNWC at daytime yield the smallest biases. The climatological analysis reveals that low-level clouds persist during the day over the coastal plains and windward side of the low mountain ranges. Conversely, on their leeward sides, i.e., over the plateaus, a decrease of the low-level cloud frequency is observed in the afternoon, together with a change from stratocumulus to cumulus. At night, the low-level cloud deck reforms over this region with the largest cloud occurrence frequencies in the morning. Vertical profiles from 2B-GEOPROF-lidar reveal cloud tops below 3000 m even at daytime. The station data and the suitable satellite products form the basis to better understand the physical processes controlling the clouds and to evaluate cloudiness from reanalyses and models.
Upstream Precursors to High-Resolution Modeled Extreme Precipitation Events in the Mountainous Regions of Southern California
Authors: De Biasio Erica F. , Georgakakos Konstantine P. 
Published: March 2023

Abstract
The enhancement of precipitation over the mountain regions of Southern California, in conjunction with mesoscale and synoptic-scale forcings, can result in high-intensity, short-duration extreme precipitation events (EPEs) that are often associated with hazardous impacts. In this study, candidate upstream atmospheric precursors at relevant spatiotemporal scales to such hazards are explored using a WRF mesoscale model with 5-km grid spacing and an hourly temporal resolution. This high-resolution model, once validated against observations, is used to discern statistically significant physics-based signals between hypothetical mesoscale forcings and the modeled precipitation response. Specifically, the role of upstream instability in modeled EPEs is indexed by convective available potential energy (CAPE) and is examined for two mountainous regions of Southern California at several lag times. A Monte Carlo approach reveals statistically significant differences between the relationship of CAPE associated with EPEs in comparison to the analogous relationship for any precipitation event. These findings hold even with accounting for the well-established role of favorably oriented low-level moisture flux in orographic precipitation. This could indicate that atmospheric instability plays a role in providing additional lifting mechanisms, in conjunction with orographic and synoptic-scale forcings, to facilitate the high short-duration precipitation intensities that have been observed in the region. This diagnostic exploratory study provides additional candidate indicators of predictability of such EPEs at higher spatiotemporal scales than previous work, based on mesoscale model physics. Further analysis should examine the identified precursors using observational data with adequate resolution.
Simultaneous Optimization of 20 Key Parameters of the Integrated Forecasting System of ECMWF Using OpenIFS. Part I: Effect on Deterministic Forecasts
Authors: Tuppi Lauri , Ekblom Madeleine , Ollinaho Pirkka , Järvinen Heikki 
Published: March 2023

Abstract
Numerical weather prediction models contain parameters that are inherently uncertain and cannot be determined exactly. It is thus desirable to have reliable objective approaches for estimation of optimal values and uncertainties of these parameters. Traditionally, the parameter tuning has been done manually, which can lead to the tuning process being a maze of subjective choices. In this paper we present how to optimize 20 key physical parameters in the atmospheric model Open Integrated Forecasting System (OpenIFS) that have a strong impact on forecast quality. The results show that simultaneous optimization of O(20) parameters is possible with O(100) algorithm steps using an ensemble of O(20) members; the results also show that the optimized parameters lead to substantial enhancement of predictive skill. The enhanced predictive skill can be attributed to reduced biases in low-level winds and upper-tropospheric humidity in the optimized model. We find that the optimization process is dependent on the starting values of the parameters that are optimized (starting from better-suited values results in a better model). The results show also that the applicability of the tuned parameter values across different model resolutions is somewhat limited because of resolution-dependent model biases, and we also found that the parameter covariances provided by the tuning algorithm seem to be uninformative.

Significance Statement
The purpose of this work is to show how to use algorithmic methods to optimize a weather model in a computationally efficient manner. Traditional manual model tuning is an extremely laborious and time-consuming process, so algorithmic methods have strong potential for saving the model developers’ time and accelerating development. This paper shows that algorithmic optimization is possible and that weather forecasts can be improved. However, potential issues related to the use of the optimized parameter values across different model resolutions are discussed as well as other shortcomings related to the tuning process.