bluuebunny/crossref_metadata_2025_split huggingface dataset:
Children’s use of demonstrative words: spatial deictics beyond infancy
Authors: GUIJARRO-FUENTES Pedro , GUDDE Harmen B. , GONZÁLEZ-PEÑA Patricia , COVENTRY Kenny R. 
Published: November 2022

AbstractDemonstrative words are one of the most important ways of establishing reference in conversation. This work describes Spanish-speaking children’s demonstrative production between ages 2 to 10 using data from the CHILDES corpora. Results indicate that children feature all demonstratives in their lexicon – however, the distal term is scarce throughout development. Moreover, patterns of demonstrative use are not adult-like at age 10. We compare adult and child data to conclude that children’s development of demonstrative production is largely protracted. Adult use of the distal demonstrative is higher than in young children, although both older children and adults use the medial term ese more than any other demonstratives. In contrast, younger children use proximals relatively more frequently than older children and adults. Suggestions for future research and theoretical implications for the Spanish demonstrative system are discussed.
The Ethical Acceptability of a Recipient’s Choice of Donor in Directed and Nondirected Transplantation: Japanese Perspective
Authors: Nakazawa Eisuke , Shaw Margie H. , Akabayashi Akira 
Published: November 2022

AbstractIn organ transplantation, there is a lack of ethical discussion about the recipient’s right not to receive a transplant. Using the current situation of living organ transplantation and deceased organ transplantation in Japan as an example, we prospectively discussed to what extent the recipient’s right not to receive a transplant is ethically acceptable. In directed transplantation from a living donor, a recipient may refuse organ donation from a particular donor. It is preferable that a recipient’s request for organ donation from a donor occurs as part of a transparent process. In nondirected transplantation from a deceased donor, refusal of transplantation from a particular type of donor appears potentially justifiable. There are both moral and pragmatic considerations. Certain refusals based solely on belief are morally unacceptable, and refusal to transplant a recipient based on the donor’s age jeopardizes the entire transplant system. When religious beliefs affect mental and physical health, individualized measures are required for transplant rejection. We also deductively developed a prospective argument based on the current status of donor–recipient communication in living organ transplantation in Japan and the 2010 amendment of the law allowing relatives to be given priority in organ transplantation from deceased donors.
Healthcare Professionals’ Conflicts When Treating Transgender Youth: Is It Necessary to Prioritize Protection Over Respect?
Authors: Hädicke Maximiliane , Föcker Manuel , Romer Georg , Wiesemann Claudia 
Published: November 2022

AbstractIncreasingly, transgender minors are seeking medical care such as puberty-suppressing or gender-affirming hormone therapies. Yet, whether these interventions should be performed at all is highly controversial. Some healthcare practitioners oppose irreversible interventions, considering it their duty to protect children from harm. Others view minors, like adults, as transgender individuals who must be protected from discrimination. The underlying ethical question is presented as a problem of priority. Is it primarily relevant that minors are involved? Or should decision makers focus on the fact that they treat transgender individuals? The paper explores the relevance for medical practice. We provide results of an interview study with German healthcare professionals. We discuss the general question whether prioritization among different group memberships of the same person is ethically defensible. We conclude that priority conflicts between group memberships of the same person can be deceptive and should be addressed by an intersectional approach. Eventually, we discuss practical implications.
Parental childhood vaccine hesitancy and predicting uptake of vaccinations: a systematic review
Authors: Obohwemu Kennedy , Christie-de Jong Floor , Ling Jonathan 
Published: November 2022

Abstract

Aim:
This review aims are to (1) identify relevant quantitative research on parental childhood vaccine hesitancy with vaccine uptake and vaccination intention being relevant outcomes and (2) map the gaps in knowledge on vaccine hesitancy to develop suggestions for further research and to guide interventions in this field.

Background:
Vaccine hesitancy recognises a continuum between vaccine acceptance and vaccine refusal, de-polarising past anti-vaccine, and pro-vaccine categorisations of individuals and groups. Vaccine hesitancy poses a serious challenge to international efforts to lessen the burden of vaccine-preventable diseases. Potential vaccination barriers must be identified to inform initiatives aimed at increasing vaccine awareness, acceptance, and uptake.

Methods:
Five databases were searched for peer-reviewed articles published between 1998 and 2020 in the fields of medicine, nursing, public health, biological sciences, and social sciences. Across these datasets, a comprehensive search technique was used to identify multiple variables of public trust, confidence, and hesitancy about vaccines. Using PRISMA guidelines, 34 papers were included so long as they focused on childhood immunisations, employed multivariate analysis, and were published during the time frame. Significant challenges to vaccine uptake or intention were identified in these studies. Barriers to vaccination for the target populations were grouped using conceptual frameworks based on the Protection Motivation Theory and the World Health Organization’s Strategic Advisory Group of Experts on Immunization Working Group model and explored using the 5C psychological antecedents of vaccination.

Findings:
Although several characteristics were shown to relate to vaccine hesitancy, they do not allow for a thorough classification or proof of their individual and comparative level of influence. Understudied themes were also discovered during the review. Lack of confidence, complacency, constraints, calculation, and collective responsibility have all been highlighted as barriers to vaccination uptake among parents to different degrees.
Breaking Up for Good
Authors: Krakowiak K. Maja 
Published: November 2022

Abstract: In recent years, entertainment scholars have investigated the extent to which negative emotions such as grief, distress, and loneliness are experienced by viewers following the departure of a favorite character or the cancellation or completion of a television series – also referred to as parasocial breakup (PSB). An online questionnaire ( N = 814) was administered to understand predictors of PSB following the end of a series as they relate to character involvement and holistic enjoyment and appreciation experiences. Findings revealed that a parasocial relationship (PSR) with a favorite character and liking of and identification with the character positively enhanced enjoyment of the series. PSR and identification also facilitated appreciation of the series. Moreover, while PSR and appreciation increased PSB, character liking and enjoyment of the series decreased it. Theoretical implications for the contrasting roles of hedonic and eudaimonic media experiences in predicting PSB are discussed.
Haline Сontrol of Unusually Deep Winter Mixing in the Gulf of Maine Investigated Using a Regional Data‐Assimilative Model
Authors: Levin J. C. , Grodsky S. A. , Vandemark D. , Wilkin J. L. 
Published: November 2022

AbstractAn unusually large positive salinity anomaly was observed across the eastern Gulf of Maine in winter 2017–2018. Buoy measurements in Jordan Basin found this anomaly extended down to at least 100 m, the deepest mixing observed in the past 19 years. Similarly, this is the strongest positive regional salt anomaly ever observed in sea surface salinity (SSS) satellite observations. To determine the source waters driving this event and to diagnose the relative importance of forcing processes, passive tracer adjoint sensitivity experiments are performed using a data assimilating version of the Regional Ocean Modeling System. The model suggests that northeastward Scotian Shelf wind anomalies is one factor in the dramatic decrease in freshwater transport to Jordan Basin, which leads to an early winter upper water column salinity surplus. This salinity change weakens the normally haline‐controlled vertical stratification across the eastern Gulf. Modeled upper ocean density and vertical diffusivity from 2007 to 2021 both show a maximum in January 2018. Winter 2017–2018 is the only period where the enhanced winter mixing extends below 100 m. Thus, anomalous vertical entrainment of saltier subsurface Gulf water is the major factor driving the extreme positive satellite‐observed SSS anomaly across the eastern Gulf including Jordan Basin. Other factors, including a modest increase in wind‐forced slope water transport, and positive fall 2017 salinity anomalies on the Scotian Shelf and Slope Sea, appear to play lesser roles in the observed salinification. The adjoint sensitivity analysis demonstrates its utility for back tracing transport pathways for periods of several months.
Non‐Stationary Probabilistic Tsunami Hazard Assessments Compounding Tides and Sea Level Rise
Authors: Sepúlveda Ignacio , Liu Philip L.‐F. , Grigoriu Mircea , Haase Jennifer S. , Winckler Patricio 
Published: November 2022

AbstractTides are often the largest source of sea levels fluctuations. Two new probabilistic tsunami hazard assessments (PTHA) methods are proposed to combine the tidal phase uncertainty at the moment of tsunami occurrence with other sources of uncertainty. The first method adopts a Stochastic Reduced Order Model (SROM) producing sets of tidal phase samples to be used in tsunami simulations. The second method uses tsunami simulations with prescribed collocation tidal phases and tide probability distributions to model the uncertainty. The methods are extended to non‐stationary probabilistic tsunami hazard assessment, compounding tsunamis, tides and sea level rise (SLR). As an illustration, these methods are applied for assessing tsunamis generated in the Manila Subduction Zone, on the coasts of Kao Hsiung and Hong Kong. While the SROM‐based method is faster solving for the PTHA if only tides are considered, the collocation‐based method is faster when both SLR and tides are considered. For the illustration case, tides have a relevant impact on PTHA results, however, the SLR within an exposure time of 100 years has stronger impact. PTHA curves of the maximum tsunami elevation are affected by tides and SLR differently. While tides and SLR increase the dispersion of PTHA hazard curve distributions, the latter also produces a translation toward higher elevations. The development of formulations based on SROM or collocation tides is the key to establishing a method which feasibly can be applied to other regions for comprehensive analysis at a global scale.
Impingement of Subsurface Anticyclonic Eddies on the Kuroshio Mainstream East of Taiwan
Authors: Wang Ran , Nan Feng , Yu Fei , Wang Bin 
Published: November 2022

AbstractThis study shows that North Pacific subtropical mode water (STMW) characterized by low potential vorticity can approach and impinge on the Kuroshio mainstream east of Taiwan. The results of the analyses of observations and output from eddy‐resolving models show that the STMW appears with the frequency of 32.1% and 19.9% in the Kuroshio east of Taiwan. A case study with the output of the ocean general circulation model for the earth simulator during October 2015–March 2016 indicates that mode water moves southwestward toward the Kuroshio in accordance with a vertically lens‐shaped subsurface anticyclonic eddy (SAE). After the shoreward edge of the SAE impinges on the offshore edge of the Kuroshio, the northward velocity, especially subsurface velocity, of the Kuroshio increases significantly in the subsurface layer and the Kuroshio central position (KCP) extends eastward. While the SAE moves and dissipates, the offshore edge of the Kuroshio moves inshore, and then transport decreases. Both the northward velocity and the KCP changes result in the Kuroshio transport change during the impingement of SAE in the case. Statistic analysis further demonstrate that eddies those can trap moving STMW are dominated by SAEs. When SAEs encounter the Kuroshio, their subsurface northward velocity increases by 67.8% and the KCP moves eastward, and thus the northward transport of the Kuroshio increases by 43.4%.
The Effects of Ocean Surface Waves on Tropical Cyclone Intensity: Numerical Simulations Using a Regional Atmosphere‐Ocean‐Wave Coupled Model
Authors: Zhao Biao , Wang Guansuo , Zhang Jun A. , Liu Li , Liu Jiping , Xu Jing , Yu Hao , Zhao Chang , Yu Xinzhu , Sun Chao , Qiao Fangli 
Published: November 2022

AbstractTropical cyclones (TCs), especially landfalling intense storms often pose serious threats to life and property in coastal areas. Although TC track forecast skill has been improved in the past decades, the progress of advancing the intensity forecast lags that of the track forecast. One possible limiting factor is the absence of ocean surface waves in forecast systems. To better represent the interaction of TC and underlying ocean, a regional atmosphere‐ocean‐wave coupled model is employed in this study. Twenty‐one TCs of a whole year in 2013 are retrospectively simulated through twin simulations, a Control and a Fully coupled run. Results show that TC intensity bias has been significantly reduced in the fully coupled simulation, in which five ocean surface wave related physical processes are considered, including wave modulation of momentum flux, sea spray effect on enthalpy flux, surface current and Stokes drift on air sea flux, non‐breaking wave induced mixing in the upper ocean as well as rain induced ocean surface cooling. A case study approach is used to diagnose the effect of individual surface wave related physical process on TC simulations. Similar to the effect of sea spray, surface waves also act as positive feedback on TC intensification by modulating air‐sea momentum flux. Absolute angular momentum budget analysis suggests that larger radial inflows and stronger updrafts near the eyewall promote the radial and vertical advections of absolute angular momentum and in turn lead to a stronger TC in Fully coupled simulation. The TC structure and size agree better with observations in Fully coupled simulation.
Assessing Drivers of Coastal Tundra Retreat at Point Hope, Alaska
Authors: Cohn Nicholas , Bosche Lauren V. , Midgley Taber , Small Christopher , Douglas Thomas A. , King Jeffrey 
Published: November 2022

AbstractShoreline erosion over the last few decades along the Point Hope, Alaska, USA coastline has led to considerable loss of tundra behind the beach. Analysis of available remote sensing, morphology, and hydrodynamic datasets are used to inform the time scales and mechanisms of coastal land loss at Point Hope, in part through integration of these data into an analytical retreat model originally developed for coastal foredunes. At shorter time scales, these analyses indicate that steeper local beach slopes influence higher wave runup that can enhance the scale of tundra retreat at a particular section of coast. Coastal stretches that are most vulnerable to wave attack of the tundra scarp appear to shift with time related to complex spatio‐temporal variability in shoreline change rates. These local beach erosion rates primarily control the retreat of the tundra at decadal scales. However, independent of the fronting beach morphology, the largest erosion events throughout the region generally occur when there is the coincidence of both high wave energy and elevated still water levels. Additional exploratory modeling results indicate that future changes to sea level and changes in wave energy will further enhance the magnitude of tundra erosion.
NRBF2-mediated autophagy contributes to metabolite replenishment and radioresistance in glioblastoma
Authors: Kim Jeongha , Kang Hyunkoo , Son Beomseok , Kim Min-Jung , Kang JiHoon , Park Kang Hyun , Jeon Jaewan , Jo Sunmi , Kim Hae Yu , Youn HyeSook , Youn BuHyun 
Published: November 2022

AbstractOvercoming therapeutic resistance in glioblastoma (GBM) is an essential strategy for improving cancer therapy. However, cancer cells possess various evasion mechanisms, such as metabolic reprogramming, which promote cell survival and limit therapy. The diverse metabolic fuel sources that are produced by autophagy provide tumors with metabolic plasticity and are known to induce drug or radioresistance in GBM. This study determined that autophagy, a common representative cell homeostasis mechanism, was upregulated upon treatment of GBM cells with ionizing radiation (IR). Nuclear receptor binding factor 2 (NRBF2)—a positive regulator of the autophagy initiation step—was found to be upregulated in a GBM orthotopic xenograft mouse model. Furthermore, ATP production and the oxygen consumption rate (OCR) increased upon activation of NRBF2-mediated autophagy. It was also discovered that changes in metabolic state were induced by alterations in metabolite levels caused by autophagy, thereby causing radioresistance. In addition, we found that lidoflazine—a vasodilator agent discovered through drug repositioning—significantly suppressed IR-induced migration, invasion, and proliferation by inhibiting NRBF2, resulting in a reduction in autophagic flux in both in vitro models and in vivo orthotopic xenograft mouse models. In summary, we propose that the upregulation of NRBF2 levels reprograms the metabolic state of GBM cells by activating autophagy, thus establishing NRBF2 as a potential therapeutic target for regulating radioresistance of GBM during radiotherapy.
The role of dendritic cells in the immunomodulation to implanted biomaterials
Authors: Wang Siyuan , Chen Yanqi , Ling Zhaoting , Li Jia , Hu Jun , He Fuming , Chen Qianming 
Published: November 2022

AbstractConsidering the substantial role played by dendritic cells (DCs) in the immune system to bridge innate and adaptive immunity, studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces, their intrinsic properties can direct their orientation and conformation, forming “biomaterial-associated molecular patterns (BAMPs)”. Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins (HSPs) and high mobility group box 1 (HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.
In vivo PDX CRISPR/Cas9 screens reveal mutual therapeutic targets to overcome heterogeneous acquired chemo-resistance
Authors: Wirth Anna-Katharina , Wange Lucas , Vosberg Sebastian , Henrich Kai-Oliver , Rausch Christian , Özdemir Erbey , Zeller Christina M. , Richter Daniel , Feuchtinger Tobias , Kaller Markus , Hermeking Heiko , Greif Philipp A. , Senft Daniela , Jurinovic Vindi , Bahrami Ehsan , Jayavelu Ashok Kumar , Westermann Frank , Mann Matthias , Enard Wolfgang , Herold Tobias , Jeremias Irmela 
Published: November 2022

AbstractResistance towards cancer treatment represents a major clinical obstacle, preventing cure of cancer patients. To gain mechanistic insights, we developed a model for acquired resistance to chemotherapy by treating mice carrying patient derived xenografts (PDX) of acute lymphoblastic leukemia with widely-used cytotoxic drugs for 18 consecutive weeks. In two distinct PDX samples, tumors initially responded to treatment, until stable disease and eventually tumor re-growth evolved under therapy, at highly similar kinetics between replicate mice. Notably, replicate tumors developed different mutations in TP53 and individual sets of chromosomal alterations, suggesting independent parallel clonal evolution rather than selection, driven by a combination of stochastic and deterministic processes. Transcriptome and proteome showed shared dysregulations between replicate tumors providing putative targets to overcome resistance. In vivo CRISPR/Cas9 dropout screens in PDX revealed broad dependency on BCL2, BRIP1 and COPS2. Accordingly, venetoclax re-sensitized derivative tumors towards chemotherapy, despite genomic heterogeneity, demonstrating direct translatability of the approach. Hence, despite the presence of multiple resistance-associated genomic alterations, effective rescue treatment for polychemotherapy-resistant tumors can be identified using functional testing in preclinical models.
EGFR-induced suppression of HPV E6/E7 is mediated by microRNA-9-5p silencing of BRD4 protein in HPV-positive head and neck squamous cell carcinoma
Authors: Nantajit Danupon , Presta Luana , Sauter Thomas , Tavassoli Mahvash 
Published: November 2022

AbstractEGFR upregulation is an established biomarker of treatment resistance and aggressiveness in head and neck cancers (HNSCC). EGFR-targeted therapies have shown benefits for HPV-negative HNSCC; surprisingly, inhibiting EGFR in HPV-associated HNSCC led to inferior therapeutic outcomes suggesting opposing roles for EGFR in the two HNSCC subtypes. The current study aimed to understand the link between EGFR and HPV-infected HNSCC particularly the regulation of HPV oncoproteins E6 and E7. We demonstrate that EGFR overexpression suppresses cellular proliferation and increases radiosensitivity of HPV-positive HNSCC cell lines. EGFR overexpression inhibited protein expression of BRD4, a known cellular transcriptional regulator of HPV E6/E7 expression and DNA damage repair facilitator. Inhibition of EGFR by cetuximab restored the expression of BRD4 leading to increased HPV E6 and E7 transcription. Concordantly, pharmacological inhibition of BRD4 led to suppression of HPV E6 and E7 transcription, delayed cellular proliferation and sensitised HPV-positive HNSCC cells to ionising radiation. This effect was shown to be mediated through EGFR-induced upregulation of microRNA-9-5p and consequent silencing of its target BRD4 at protein translational level, repressing HPV E6 and E7 transcription and restoring p53 tumour suppressor functions. These results suggest a novel mechanism for EGFR inhibition of HPV E6/E7 oncoprotein expression through an epigenetic pathway, independent of MAPK, but mediated through microRNA-9-5p/BRD4 regulation. Therefore, targeting EGFR may not be the best course of therapy for certain cancer types including HPV-positive HNSCC, while targeting specific signalling pathways such as BRD4 could provide a better and potentially new treatment to improve HNSCC therapeutic outcome.