bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceptions of telemedicine at a pediatric otolaryngology-head and neck surgery program
Authors: Gwilt Claire , Metzger Gregory , Jatana Kris , Bourgeois Tran , Walz Patrick 
Published: November 2022

ObjectiveWith few studies investigating the effectiveness of telemedicine (TM) in pediatric otolaryngology (ear, nose, and throat; ENT), its role in clinical practice is unclear. The objective of this study was to investigate provider perspectives regarding utility of TM in pediatric ENT practice.MethodsA survey gauging the relative merits of TM visits for common pediatric ENT chief complaints and postoperative visits was distributed to all pediatric ENT providers at a tertiary care, free-standing children’s hospital. Respondents were asked to assess the effectiveness of TM visits compared with in-person visits for completing the following tasks: history collection, physical examination, medical decision-making, and patient counseling.ResultsProviders rated TM visits as less useful than in-person visits for completing the most predefined tasks but did identify advantages in history taking via TM for the majority of complaints. Compared with providers with ≥10 years of experience, those with <10 years of experience found TM to be more effective than the in-person appointment for making clinical decisions for patients presenting with recurrent/chronic pharyngitis, neck masses, and stridor/noisy breathing. Opinions regarding the utility of TM for postoperative visits were mixed, with adenoidectomy, tonsillectomy and superficial procedures being most frequently deemed appropriate for TM.ConclusionsThe introduction of TM to pediatric ENT faces limitations in detailed examination of areas not accessible without specialized instrumentation. Due to its strength in history taking, results suggest an asynchronous, ‘store and forward’ encounter followed by an in-person physical examination to confirm the diagnosis and treatment plan could be beneficial.
Inverse method applied to autonomous broadband hydroacoustic survey detects higher densities of zooplankton in near-surface aggregations than vessel-based net survey
Authors: Dunn Muriel , Pedersen Geir , Basedow Sünnje L. , Daase Malin , Falk-Petersen Stig , Bachelot Loïc , Camus Lionel , Geoffroy Maxime 
Published: November 2022

Throughout all oceans, aggregations of zooplankton and ichthyoplankton appear as horizontal sound scattering layers (SSLs) when detected with active acoustic techniques. Quantifying the composition and density of these layers is prone to sampling biases. We conducted a net and trawl survey of the epipelagic fauna in northern Norway (70° N) in June 2018 while an autonomous surface vehicle equipped with a broadband echosounder (283–383 kHz) surveyed the same region. Densities from the autonomous hydroacoustic survey were calculated using forward estimates from the relative density from the net and trawl, and inversion estimates with statistical data-fitting. All four methods (net, trawl, acoustic forward and inverse methods) identified that copepods dominated the epipelagic SSL, while pteropods, amphipods and fish larvae were present in low densities. The density estimates calculated with the inverse method were higher for mobile zooplankton, such as euphausiid larvae, than with the other methods. We concluded that the inverse method applied to broadband autonomous acoustic surveys can improve density estimates of epipelagic organisms by diminishing avoidance biases and increasing the spatio-temporal resolution of ship-based surveys.
Design and Preclinical Evaluation of a Novel B7-H4–Directed Antibody–Drug Conjugate, AZD8205, Alone and in Combination with the PARP1-Selective Inhibitor AZD5305
Authors: Kinneer Krista , Wortmann Philipp , Cooper Zachary A. , Dickinson Niall J. , Masterson Luke , Cailleau Thais , Hutchinson Ian , Vijayakrishnan Balakumar , McFarlane Mary , Ball Kathryn , Davies Michael , Lewis Arthur , Huang Yue , Rosenbaum Anton I. , Yuan Jiaqi , Chesebrough Jon , Anderton Judith , Monks Noel , Novick Steven , Wang Jixin , Dimasi Nazzareno , Christie R. James , Sabol Darrin , Tosto Frances Anne , Wallez Yann , Leo Elisabetta , Albertella Mark R. , Staniszewska Anna D. , Tice David A. , Howard Philip W. , Luheshi Nadia , Sapra Puja 
Published: November 2022

AbstractPurpose:We evaluated the activity of AZD8205, a B7-H4–directed antibody–drug conjugate (ADC) bearing a novel topoisomerase I inhibitor (TOP1i) payload, alone and in combination with the PARP1-selective inhibitor AZD5305, in preclinical models.Experimental Design:IHC and deep-learning–based image analysis algorithms were used to assess prevalence and intratumoral heterogeneity of B7-H4 expression in human tumors. Several TOP1i-ADCs, prepared with Val-Ala or Gly–Gly–Phe–Gly peptide linkers, with or without a PEG8 spacer, were compared in biophysical, in vivo efficacy, and rat toxicology studies. AZD8205 mechanism of action and efficacy studies were conducted in human cancer cell line and patient-derived xenograft (PDX) models.Results:Evaluation of IHC-staining density on a per-cell basis revealed a range of heterogeneous B7-H4 expression across patient tumors. This informed selection of bystander-capable Val-Ala–PEG8–TOP1i payload AZ14170133 and development of AZD8205, which demonstrated improved stability, efficacy, and safety compared with other linker–payload ADCs. In a study of 26 PDX tumors, single administration of 3.5 mg/kg AZD8205 provided a 69% overall response rate, according to modified RECIST criteria, which correlated with homologous recombination repair (HRR) deficiency (HRD) and elevated levels of B7-H4 in HRR-proficient models. Addition of AZD5305 sensitized very low B7-H4–expressing tumors to AZD8205 treatment, independent of HRD status and in models representing clinically relevant mechanisms of PARPi resistance.Conclusions:These data provide evidence for the potential utility of AZD8205 for treatment of B7-H4–expressing tumors and support the rationale for an ongoing phase 1 clinical study (NCT05123482).See related commentary by Pommier and Thomas, p. 991
IL1β Expression Driven by Androgen Receptor Absence or Inactivation Promotes Prostate Cancer Bone Metastasis
Authors: DiNatale Anthony , Worrede Asurayya , Iqbal Waleed , Marchioli Michael , Toth Allison , Sjöström Martin , Zhu Xiaolin , Corey Eva , Feng Felix Y. , Zhou Wanding , Fatatis Alessandro 
Published: November 2022

We report the inverse association between the expression of androgen receptor (AR) and IL1β in a cohort of patients with metastatic castration-resistant prostate cancer. We also discovered that AR represses the IL1β gene by binding an androgen response element half-site located within the promoter, which explains the IL1β expression in AR-negative (ARNEG) cancer cells. Consistently, androgen depletion or AR-pathway inhibitors (ARI) derepressed IL1β in AR-positive cancer cells, both in vitro and in vivo. The AR transcriptional repression is sustained by histone deacetylation at the H3K27 mark in the IL1β promoter. Notably, patients’ data suggest that DNA methylation prevents IL1β expression, even if the AR-signaling axis is inactive. Our previous studies show that secreted IL1β supports metastatic progression in mice by altering the transcriptome of tumor-associated bone stroma. Thus, in patients with prostate cancer harboring ARNEG tumor cells or treated with androgen-deprivation therapy/ARIs, and with the IL1β gene unmethylated, IL1β could condition the metastatic microenvironment to sustain disease progression.Significance:IL1β plays a crucial role in promoting skeletal metastasis. The current standard of care for patients with prostate cancer inhibits the AR-signaling axis in tumor cells and will consequently unleash IL1β production. Thus, hormonal deprivation and AR inhibitors should be combined with targeting IL1β signaling, and screening for DNA methylation on the IL1β locus will identify patients that benefit the most from this approach.
Independent Associations of Education, Intelligence, and Cognition With Hypertension and the Mediating Effects of Cardiometabolic Risk Factors: A Mendelian Randomization Study
Authors: Wang Yiying , Ye Chaojie , Kong Lijie , Zheng Jie , Xu Min , Xu Yu , Li Mian , Zhao Zhiyun , Lu Jieli , Chen Yuhong , Wang Weiqing , Ning Guang , Bi Yufang , Wang Tiange 
Published: November 2022

Background:
Education, intelligence, and cognition are associated with hypertension, but which one plays the most prominent role in the pathogenesis of hypertension and which modifiable risk factors mediate the causal effects remains unknown.

Methods:
Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted 2-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, or cognition on hypertension (FinnGen study, 70 651 cases/223 663 controls; UK Biobank, 77 723 cases/330 366 controls) and blood pressure (International Consortium of Blood Pressure, 757 601 participants), and used 2-step Mendelian randomization to evaluate 25 potential mediators of the association and calculate the mediated proportions.

Results:
Meta-analysis of inverse variance weighted Mendelian randomization results from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.2 years) higher education was associated with 44% (95% CI: 0.40–0.79) decreased hypertension risk and 1.682 mm Hg lower systolic and 0.898 mm Hg lower diastolic blood pressure, independently of intelligence and cognition. While the causal effects of intelligence and cognition on hypertension were not independent of education; 6 out of 25 cardiometabolic risk factors were identified as mediators of the association between education and hypertension, ranked by mediated proportions, including body mass index (mediated proportion: 30.1%), waist-to-hip ratio (22.8%), body fat percentage (14.1%), major depression (7.0%), high-density lipoprotein cholesterol (4.7%), and triglycerides (3.4%). These results were robust to sensitivity analyses.

Conclusions:
Our findings illustrated the causal, independent impact of education on hypertension and blood pressure and outlined cardiometabolic mediators as priority targets for prevention of hypertension attributable to low education.
Dynamics of Functional Networks for Syllable and Word-Level Processing
Authors: Rimmele Johanna M. , Sun Yue , Michalareas Georgios , Ghitza Oded , Poeppel David 
Published: November 2022

Abstract
Speech comprehension requires the ability to temporally segment the acoustic input for higher-level linguistic analysis. Oscillation-based approaches suggest that low-frequency auditory cortex oscillations track syllable-sized acoustic information and therefore emphasize the relevance of syllabic-level acoustic processing for speech segmentation. How syllabic processing interacts with higher levels of speech processing, beyond segmentation, including the anatomical and neurophysiological characteristics of the networks involved, is debated. In two MEG experiments, we investigate lexical and sublexical word-level processing and the interactions with (acoustic) syllable processing using a frequency-tagging paradigm. Participants listened to disyllabic words presented at a rate of 4 syllables/s. Lexical content (native language), sublexical syllable-to-syllable transitions (foreign language), or mere syllabic information (pseudo-words) were presented. Two conjectures were evaluated: (i) syllable-to-syllable transitions contribute to word-level processing; and (ii) processing of words activates brain areas that interact with acoustic syllable processing. We show that syllable-to-syllable transition information compared to mere syllable information, activated a bilateral superior, middle temporal and inferior frontal network. Lexical content resulted, additionally, in increased neural activity. Evidence for an interaction of word- and acoustic syllable-level processing was inconclusive. Decreases in syllable tracking (cerebroacoustic coherence) in auditory cortex and increases in cross-frequency coupling between right superior and middle temporal and frontal areas were found when lexical content was present compared to all other conditions; however, not when conditions were compared separately. The data provide experimental insight into how subtle and sensitive syllable-to-syllable transition information for word-level processing is.
Lagrangian Overturning Pathways in the Eastern Subpolar North Atlantic
Authors: Tooth Oliver J. , Johnson Helen L. , Wilson Chris 
Published: November 2022

Abstract
The strength of the Atlantic meridional overturning circulation (AMOC) at subpolar latitudes is dominated by water mass transformation in the eastern subpolar North Atlantic Ocean (SPNA). However, the distribution of this overturning across the individual circulation pathways of both the Subpolar Gyre (SPG) and the Nordic seas overflows remains poorly understood. Here, we introduce a novel Lagrangian measure of the density-space overturning to quantify the principal pathways of the time-mean overturning circulation within an eddy-permitting ocean model hindcast. By tracing the trajectories of water parcels initialized from the northward inflows across the Overturning in the Subpolar North Atlantic Program (OSNAP) East section, we show that water mass transformation along the pathways of the eastern SPG accounts for 55% of the mean strength of the eastern subpolar AMOC. Water parcels following the dominant SPG pathway, sourced from the Subarctic Front, form upper North Atlantic Deep Water by circulating horizontally across sloping isopycnals in less than 2 years. A slower SPG route, entrained by overflow waters south of the Iceland–Faroes Ridge, is a crucial conduit for subtropical-origin water masses to penetrate the deep ocean on subdecadal time scales. On reproducing our findings using time-averaged velocity and hydrographic fields, we further show that the Nordic seas overflow pathways integrate multiple decades of water mass transformation before returning across the Greenland–Scotland Ridge. We propose that the strong disparity between the overturning time scales of the SPG (interannual) and the Nordic seas overflows (multidecadal) has important implications for the propagation of density anomalies within the eastern SPNA and hence the sources of AMOC variability.
Linking Large-Scale Double-ITCZ Bias to Local-Scale Drizzling Bias in Climate Models
Authors: Zhou Wenyu , Leung L. Ruby , Lu Jian 
Published: November 2022

Abstract
Tropical precipitation in climate models presents significant biases in both the large-scale pattern (i.e., double intertropical convergence zone bias) and local-scale characteristics (i.e., drizzling bias with too frequent drizzle/convection and reduced occurrences of no and heavy precipitation). By untangling the coupled system and analyzing the biases in precipitation, cloud, and radiation, this study shows that local-scale drizzling bias in atmospheric models can lead to large-scale double-ITCZ bias in coupled models by inducing convective-regime-dependent biases in precipitation and cloud radiative effects (CRE). The double-ITCZ bias consists of a hemispherically asymmetric component that arises from the asymmetric SST bias and a nearly symmetric component that exists in atmospheric models without the SST bias. By increasing light rain but reducing heavy rain, local-scale drizzling bias induces positive (negative) precipitation bias in the moderate (strong) convective regime, leading to the nearly symmetric wet bias in atmospheric models. By affecting the cloud profile, local-scale drizzling bias induces positive (negative) CRE bias in the stratocumulus (convective) regime in atmospheric models. Because the stratocumulus (convective) region is climatologically more pronounced in the southern (northern) tropics, the CRE bias is deemed to be hemispherically asymmetric and drives warm and wet (cold and dry) biases in the southern (northern) tropics when coupled to ocean. Our results suggest that correcting local-scale drizzling bias is critical for fixing large-scale double-ITCZ bias. The drizzling and double-ITCZ biases are not alleviated in models with mesoscale (0.25°–0.5°) or even storm-resolving (∼3 km) resolution, implying that either large-eddy simulation or fundamental improvement in small-scale subgrid parameterizations is needed.
Modulation by the QBO of the Relationship between the NAO and Northeast China Temperature in Late Winter
Authors: Zuo Jinqing , Xie Fei , Yang Liuni , Sun Chenghu , Wang Lin , Zhang Ruhua 
Published: November 2022

Abstract
The North Atlantic Oscillation (NAO) generally has an in-phase relationship with surface air temperature (SAT) anomalies over Northeast China in late winter. The present study shows that such an NAO–SAT relationship becomes stronger during easterly phases of the quasi-biennial oscillation (QBO), but is relatively weak during westerly phases. Observational evidence reveals that the modulation effect of the QBO on the NAO–SAT relationship over Northeast China is attributable to QBO-induced changes in the spatial structure of the NAO and associated stratosphere–troposphere coupling. During easterly QBO phases, the NAO has a strong connection with the Northern Hemisphere stratospheric polar vortex, facilitating a hemisphere-wide structure of the NAO and thus a downstream extension of NAO signal from the Euro–Atlantic sector toward Northeast Asia. During westerly QBO phases, however, the NAO has a limited connection with the stratospheric polar vortex. In this case, the NAO features a classically regional mode, with the signal in the SAT field mainly confined to the Euro-Atlantic sector. By examining historical simulations from six climate models participating in CMIP6 and including stratospheric processes, it is found that none of these models captures a significant difference in the spatial structure of the NAO and its connection with the stratospheric polar vortex between the easterly and westerly QBO phases in late winter. A key reason may be related to the poor performance of the models in simulating the Holton–Tan effect, which is critical for linking the QBO and NAO.

Significance Statement
The QBO is the dominant mode of equatorial stratospheric variability and important for seasonal forecasting. This study aims to better understand the surface influence of the QBO by examining the relationship between the NAO and temperature anomalies over China according to the phases of the QBO during boreal winter. Our results highlight the importance of the QBO in modulating the spatial structure and thus climate impact of the NAO via stratosphere–troposphere coupling in observations, while state-of-the-art climate models perform poorly in simulating the QBO-related stratosphere–troposphere coupling and thus the QBO–NAO connection. These findings have important implications for seasonal prediction and model development in the future.
Simulated Mid-Holocene and Last Interglacial Climate Using Two Generations of AWI-ESM
Authors: Shi Xiaoxu , Werner Martin , Wang Qiang , Yang Hu , Lohmann Gerrit 
Published: November 2022

Abstract
Numerical simulations allow us to gain a comprehensive understanding of the underlying mechanisms of past, present, and future climate changes. The mid-Holocene (MH) and the last interglacial (LIG) were the two most recent warm episodes of Earth’s climate history and are the focus of paleoclimate research. Here, we present results of MH and LIG simulations with two versions of the state-of-the-art Earth system model AWI-ESM. Most of the climate changes in MH and LIG compared to the preindustrial era are agreed upon by the two model versions, including 1) enhanced seasonality in surface temperature that is driven by the redistribution of seasonal insolation; 2) a northward shift of the intertropical convergence zone (ITCZ) and tropical rain belt; 3) a reduction in annual mean Arctic sea ice concentration; 4) weakening and northward displacement of the Northern Hemisphere Hadley circulation, which is related to the decrease and poleward shift of the temperature gradient from the subtropical to the equator in the Northern Hemisphere; 5) a westward shift of the Indo-Pacific Walker circulation due to anomalous warming over the Eurasia and North Africa during boreal summer; and 6) an expansion and intensification of Northern Hemisphere summer monsoon rainfall, with the latter being dominated by the dynamic component of moisture budget (i.e., the strengthening of wind circulation). However, the simulated responses of the Atlantic meridional overturning circulation (AMOC) in the two models yield different results for both the LIG and the MH. AMOC anomalies between the warm interglacial and preindustrial periods are associated with changes in North Atlantic westerly winds and stratification of the water column at the North Atlantic due to changes in ocean temperature, salinity, and density.
Can DSD Assumptions Explain the Differences in Satellite Estimates of Warm Rain?
Authors: Schulte Richard M. , Kummerow Christian D. 
Published: November 2022

Abstract
Satellite-based oceanic precipitation estimates, particularly those derived from the Global Precipitation Measurement (GPM) satellite and CloudSat, suffer from significant disagreement over regions of the globe where warm rain processes are dominant. GPM estimates of average rain rate tend to be lower than CloudSat estimates, due in part to GPM being less sensitive to shallow and/or light precipitation. Using coincident observations between GPM and CloudSat, we find that the GPM_2BCMB product misses about two-thirds of total accumulated warm rain compared to the CloudSat 2C-RAIN-PROFILE product. This difference becomes much smaller when products are compared at 1000 m above the surface (mitigating surface clutter issues) and when forcing the frequency of rain from CloudSat to match the frequency from GPM (mitigating sensitivity issues). However, even then a gap of about 25% remains. Using an optimal estimation retrieval algorithm on the underlying data, we retrieve a similar result, but find that the remaining difference between the GPM and CloudSat retrieved rain rates can be almost entirely accounted for by inconsistent assumptions about the shape of the drop size distribution (DSD) that are made in the two retrievals. We conclude that DSD assumptions contribute significantly to the relative underestimation of warm rain by GPM compared to CloudSat. Because the choice of DSD model has such a large effect on retrieved rain rates, more work is needed to determine whether the DSD models assumed by either the GPM_2BCMB or 2C-RAIN-PROFILE algorithms are actually appropriate for warm rain.