bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bispecific γδ T-cell Engager Targeting EGFR Activates a Potent Vγ9Vδ2 T cell–Mediated Immune Response against EGFR-Expressing Tumors
Authors: King Lisa A. , Toffoli Elisa C. , Veth Myrthe , Iglesias-Guimarais Victoria , Slot Manon C. , Amsen Derk , van de Ven Rieneke , Derks Sarah , Fransen Marieke F. , Tuynman Jurriaan B. , Riedl Thilo , Roovers Rob C. , Adang Anton E.P. , Ruben Jurjen M. , Parren Paul W.H.I. , de Gruijl Tanja D. , van der Vliet Hans J. 
Published: June 2023

Abstract
Vγ9Vδ2 T cells are effector cells with proven antitumor efficacy against a broad range of cancers. This study aimed to assess the antitumor activity and safety of a bispecific antibody directing Vγ9Vδ2 T cells to EGFR-expressing tumors. An EGFR-Vδ2 bispecific T-cell engager (bsTCE) was generated, and its capacity to activate Vγ9Vδ2 T cells and trigger antitumor activity was tested in multiple in vitro, in vivo, and ex vivo models. Studies to explore safety were conducted using cross-reactive surrogate engagers in nonhuman primates (NHP). We found that Vγ9Vδ2 T cells from peripheral blood and tumor specimens of patients with EGFR+ cancers had a distinct immune checkpoint expression profile characterized by low levels of PD-1, LAG-3, and TIM-3. Vγ9Vδ2 T cells could be activated by EGFR-Vδ2 bsTCEs to mediate lysis of various EGFR+ patient–derived tumor samples, and substantial tumor growth inhibition and improved survival were observed in in vivo xenograft mouse models using peripheral blood mononuclear cells (PBMC) as effector cells. EGFR-Vδ2 bsTCEs exerted preferential activity toward EGFR+ tumor cells and induced downstream activation of CD4+ and CD8+ T cells and natural killer (NK) cells without concomitant activation of suppressive regulatory T cells observed with EGFR-CD3 bsTCEs. Administration of fully cross-reactive and half-life extended surrogate engagers to NHPs did not trigger signals in the safety parameters that were assessed. Considering the effector and immune-activating properties of Vγ9Vδ2 T cells, the preclinical efficacy data and acceptable safety profile reported here provide a solid basis for testing EGFR-Vδ2 bsTCEs in patients with EGFR+ malignancies.
Using Environmental Litigation to Advance Ecological Restoration under the Convention on Biological Diversity in China
Authors: Rong Zhenzhen 
Published: June 2023

Abstract
In response to unprecedented global biodiversity loss, the obligation of restoration has been integrated into the Convention on Biological Diversity (CBD, or Convention). As a Party to the CBD, China has implemented restoration commitments through the ‘National Biodiversity Strategy and Action Plan (2011–2030)’. This article focuses on how such commitments have been translated into the Chinese legal framework and environmental litigation, and how environmental litigation can advance ecological restoration. There exist restoration obligations of governments and individuals. When they fail to fulfil their restoration obligations or cause damage to ecosystems, their wrong actions or inactions can be corrected through restoration orders imposed by Chinese courts, namely primary restoration orders and alternative restoration orders. Also, some weaknesses exist due to relying on forcing defendants to pay to restore damaged ecosystems, including that alternative restoration funds could be misappropriated, and the current legal mechanisms could incentivize a ‘license to trash’ style culture.
A market
Authors: Osborne Martin J. , Rubinstein Ariel 
Published: June 2023

This chapter, unlike in the previous one, assumes that the ownership of a house is recognized and protected. Each house is initially owned by some individual. Houses can be exchanged only with the mutual consent of both owners; no individual can force another individual to give up her house.
The model allows us to introduce the central economic idea of prices as a means of guiding the individuals to a reallocation of the houses in which no group of individuals want to voluntarily exchange their houses.
A market
Authors: Osborne Martin J. , Rubinstein Ariel 
Published: June 2023

This chapter, unlike in the previous one, assumes that the ownership of a house is recognized and protected. Each house is initially owned by some individual. Houses can be exchanged only with the mutual consent of both owners; no individual can force another individual to give up his house.
The model allows us to introduce the central economic idea of prices as a means of guiding the individuals to a reallocation of the houses in which no group of individuals want to voluntarily exchange their houses.
Lagrangian and Eulerian Supersaturation Statistics in Turbulent Cloudy Rayleigh–Bénard Convection: Applications for LES Subgrid Modeling
Authors: Chandrakar Kamal Kant , Morrison Hugh , Shaw Raymond A. 
Published: June 2023

Abstract
Turbulent fluctuations of scalar and velocity fields are critical for cloud microphysical processes, e.g., droplet activation and size distribution evolution, and can therefore influence cloud radiative forcing and precipitation formation. Lagrangian and Eulerian water vapor, temperature, and supersaturation statistics are investigated in direct numerical simulations (DNS) of turbulent Rayleigh–Bénard convection in the Pi Convection Cloud Chamber to provide a foundation for parameterizing subgrid-scale fluctuations in atmospheric models. A subgrid model for water vapor and temperature variances and covariance and supersaturation variance is proposed, valid for both clear and cloudy conditions. Evaluation of phase change contributions through an a priori test using DNS data shows good performance of the model. Supersaturation is a nonlinear function of temperature and water vapor, and relative external fluxes of water vapor and heat (e.g., during entrainment-mixing and phase change) influence turbulent supersaturation fluctuations. Although supersaturation has autocorrelation and structure functions similar to the independent scalars (temperature and water vapor), the autocorrelation time scale of supersaturation differs. Relative scalar fluxes in DNS without cloud make supersaturation PDFs less skewed than the adiabatic case, where they are highly negatively skewed. However, droplet condensation changes the PDF shape response: it becomes positively skewed for the adiabatic case and negatively skewed when the sidewall relative fluxes are large. Condensation also increases correlations between water vapor and temperature in the presence of relative scalar fluxes but decreases correlations for the adiabatic case. These changes in correlation suppress supersaturation variability for the nonadiabatic cases and increase it for the adiabatic case. Implications of this work for subgrid microphysics modeling using a Lagrangian stochastic scheme are also discussed.
A Surface Radiation Balance Dataset from Siple Dome in West Antarctica for Atmospheric and Climate Model Evaluation
Authors: Lubin Dan , Ghiz Madison L. , Castillo Sergio , Scott Ryan C. , LeBlanc Samuel E. , Silber Israel 
Published: June 2023

Abstract
A field campaign at Siple Dome in West Antarctica during the austral summer 2019/20 offers an opportunity to evaluate climate model performance, particularly cloud microphysical simulation. Over Antarctic ice sheets and ice shelves, clouds are a major regulator of the surface energy balance, and in the warm season their presence occasionally induces surface melt that can gradually weaken an ice shelf structure. This dataset from Siple Dome, obtained using transportable and solar-powered equipment, includes surface energy balance measurements, meteorology, and cloud remote sensing. To demonstrate how these data can be used to evaluate model performance, comparisons are made with meteorological reanalysis known to give generally good performance over Antarctica (ERA5). Surface albedo measurements show expected variability with observed cloud amount, and can be used to evaluate a model’s snowpack parameterization. One case study discussed involves a squall with northerly winds, during which ERA5 fails to produce cloud cover throughout one of the days. A second case study illustrates how shortwave spectroradiometer measurements that encompass the 1.6-μm atmospheric window reveal cloud phase transitions associated with cloud life cycle. Here, continuously precipitating mixed-phase clouds become mainly liquid water clouds from local morning through the afternoon, not reproduced by ERA5. We challenge researchers to run their various regional or global models in a manner that has the large-scale meteorology follow the conditions of this field campaign, compare cloud and radiation simulations with this Siple Dome dataset, and potentially investigate why cloud microphysical simulations or other model components might produce discrepancies with these observations.

significance statement
Antarctica is a critical region for understanding climate change and sea level rise, as the great ice sheets and the ice shelves are subject to increasing risk as global climate warms. Climate models have difficulties over Antarctica, particularly with simulation of cloud properties that regulate snow surface melting or refreezing. Atmospheric and climate-related field work has significant challenges in the Antarctic, due to the small number of research stations that can support state-of-the-art equipment. Here we present new data from a suite of transportable and solar-powered instruments that can be deployed to remote Antarctic sites, including regions where ice shelves are most at risk, and we demonstrate how key components of climate model simulations can be evaluated against these data.
Influence of Underlying Surface Datasets on Simulated Hydrological Variables in the Xijiang River Basin
Authors: Liu Songnan , Wang Jun , Wang Huijun , Ge Shilong 
Published: June 2023

Abstract
Hydrological models play an important role in water resources management and extreme events forecasting, and they are sensitive to the underlying conditions. This study aims to evaluate the impact of different soil-type maps and land-use maps on hydrological simulations and watershed responses by applying the WRF-Hydro (Weather Research and Forecasting Model Hydrological modeling system) distributed hydrological model to the Xijiang River basin. WRF-Hydro runs for four different scenarios for the period 1992–2013. FAO (Food and Agriculture Organization) and GSDE (Global Soil Dataset for Earth System Science) soil-type maps, and MODIS (Moderate-Resolution Imaging Spectroradiometer) and CNLUCC (China Land Use Land Cover Remote Sensing Monitoring Dataset) land-use maps are used in this study. These soil-type maps and land-use maps are freely combined to form four scenarios. It is found that soil moisture and surface runoff are sensitive to soil-type maps, and absorbed shortwave radiation is found to be the least sensitive to soil-type maps. Absorbed shortwave radiation and heat flux are sensitive to land-use maps. The model performance of simulating soil moisture has increased when the soil-type map changes from FAO to GSDE and the land-use map changes from MODIS to CNLUCC for most stations. When the soil-type map changes from FAO to GSDE and the land-use map changes from MODIS to CNLUCC, the biases of simulating streamflow decrease. This study shows that the performance of the offline WRF-Hydro is significantly influenced by soil-type and land-use maps, and better simulation results can be obtained with more realistic underlying surface maps.

Significance Statement
The purpose of this study is to evaluate the impacts of land-use and soil-type maps on hydrological processes at the watershed scale by applying a distributed hydrological model WRF-Hydro model for the Xijiang River basin and reveal the importance of choosing land-use and soil-type maps. In this study, two soil-type maps and two land-use maps are used. It is found that soil moisture and surface runoff are sensitive to soil-type maps, and absorbed shortwave radiation and heat flux are sensitive to land-use maps. When using GSDE soil-type and CNLUCC land-use maps, the performance of the model is improved. The underlying conditions should be considered when applying the models in practice.
Children as social actors negotiating their privacy in the digital commercial context
Authors: Srivastava Sonali , Wilska Terhi-Anna , Nyrhinen Jussi 
Published: June 2023

This study advances research on children’s negotiation of online commercial privacy by identifying an act of digital agency by children that may serve their current needs but can also impact children negatively. Secondly, it identifies certain factors children consider while evaluating the trustworthiness of apps and websites before disclosing information online. Eight focus group discussions with children (13–16 years) in Finland’s capital region are analysed using thematic analysis. Our findings highlight that while children’s digital literacy education is needed, ensuring that education translates to children’s online practices is also essential. We also recommend increasing corporations’ accountability in ensuring children’s privacy.
DOT1L Epigenetically Regulates Autophagy and Mitochondria Fusion in Cell Lines of Renal Cancer
Authors: Hou Yanguang , Liu Jiachen , Huang Shiyu , Wang Lei , Hu Juncheng , Liu Xiuheng 
Published: June 2023

Objectives DOT1L, a histone methylase, is overexpression in renal cell cancer. However, the role and detailed molecular mechanism of DOT1L involved in renal cancer development remain unknown. Methods The inhibition of DOT1L was used by SGC0946 and short hairpin RNA silencing. Monodansylcadaverine staining and transmission electron microscope were performed to detect autophagy changes as a result of the inhibition of DOT1L. MitoTracker Red assay was used to analyze mitochondrial morphology. The autophagy markers and mitochondria-related proteins were analyzed by Western blot, qPCR, or immunofluorescence. ChIP assay was performed to demonstrate H3K79me2 is involved in the direct regulation of Farnesoid X receptor transcription. Results DOT1L inhibition increased autophagy activity and promoted mito chondria fusion in cell lines of renal cancer. Inhibition of DOT1L upregulated levels of LC3α/β, P62, MFN1, and MFN2, which contributed to autophagy activity or mitochondria fusion. DOT1L knockdown showed a similar the above process. DOT1L inhibition or silencing resulted in AMP-activated protein kinase activation and mammalian target of rapamycin inhibition. Mechanistically, the DOT1L inhibitor and its short hairpin RNAs decreased the expression of Farnesoid X receptor in a histone methylase-dependent manner. Conclusion We revealed the essential role of Farnesoid X receptor in regulating DOT1L-induced autophagy and mitochondrial fission through the AMP-activated protein kinase/mammalian target of rapamycin pathway in cell lines of renal cancer, which may provide new insights into the pathogenesis of renal cell cancer.
Architectural Design Qualities of an Adolescent Psychiatric Hospital to Benefit Patients and Staff
Authors: Norouzi Neda , Martinez Antonio , Rico Zayra 
Published: June 2023

Objectives: This study is focused on how architectural design of adolescent psychiatric hospitals could positively affect not only patients but also staff members working at the hospitals. Background: Adolescents between the ages of 12 and 18 are among the young population with the highest percentage of mental illness. However, there are limited number of intentionally designed psychiatric hospitals for adolescents. Staff who work in adolescent psychiatric hospitals may face workplace violence. Studies on environmental impacts suggest that the built environment affects patients’ well-being and safety as well as staff’s satisfaction, working condition, safety, and health. However, there are very few studies that focus on adolescent psychiatric hospitals and the impact of the built environment on both staff and patients. Methods: Data were collected through literature analysis and semi-structured interviews with staff of three psychiatric state hospitals with adolescent patient units. The triangulation of multiple data sources informed a set of environmental design conditions that captures the complexity and connectedness of architectural design and the occupants of an adolescent psychiatric hospital. Results: The results present architectural composition, atmosphere, lighting, natural environment, safety, and security as indispensable design conditions to create an enclosed and city-like campus that provides a serene, secure, and structured environment that benefit staff and adolescent patients. Conclusion: The specific design strategies that need to be incorporated in the architectural design of a safe and secure adolescent psychiatric hospital include an open floor plan that respects patients’ autonomy and offers privacy while always providing staff with full visibility of patients.
Analysis of outcome of prostatic UroLift placement in benign prostatic hyperplasia in a district hospital
Authors: Biswas Krishnendu , Ahmed Saad , Soundararasha Kasthury , Rix Gerald , Pillai Rajiv , Maan Zafar , Keoghane Stephen , Datta Soumendra Nath 
Published: June 2023

Aims and Objective: To analyse the outcome of prostatic UroLift (PUL) placement done at our hospital for the treatment of benign prostatic hyperplasia (BPH). Materials and Methods: Demographic and perioperative data were collected for all patients who underwent PUL placement for BPH at out hospital from December 2017 to January 2020. International prostate symptom score (IPSS), quality of life (QoL), maximum urinary flow rate (Q-max), complications and requirement of auxiliary procedures were noted till date. Mann–Whitney U test was used to compare the pre- and post-operative parameters. Results: A total of 45 patients underwent PUL placement and were followed up for a median period of 26 months (range 14–37 months). The median age of the patients and prostate volume were 76 years (range 54–90 years) and 50 mL (range 30–70 mL), respectively. Five patients had median lobe. An average of 3.2 ± 1.1 clips were placed. The mean IPSS, QoL and Q-max in the pre-operative and latest follow-up period were 19.3 ± 5.9 and 11.1 ± 5.6 ( p < 0.001), 4.3 ± 1.1 and 2.5 ± 1.4 ( p < 0.001), 9.8 ± 5.0 mL/s and 12.8 ± 6.2 mL/s ( p = 0.004), respectively. Complications were dysuria (one patient, 2.2%), urinary tract infection (one patient, 2.2%), haematuria (one patient, 2.2%), transient urinary retention (two patients, 4.4%), post-void dribbling (two patients, 4.4%), bladder stone (one patient, 2.2%) and clip migration (one patient 2.2%). Six patients (13.3%) required auxiliary treatment in follow-up. Conclusion: PUL placement improved the IPSS, QoL and Q-max significantly over a median follow-up of 26 months with retreatment rate of 13.3%. It is a safe procedure with few easily manageable complications. Level of evidence: Not applicable
Resident Physician Education in the Human Trafficking Medical Safe Haven
Authors: Kelly Kiersten , Gibson Matthew , Chambers Ronald 
Published: June 2023

INTRODUCTION Human trafficking is a widespread public health problem across the United States. In recognition of the incredible need among victims and survivors of human trafficking for longitudinal, trauma-informed care, the Medical Safe Haven (MSH) was developed in 2016 through the Dignity Health Family Medicine Residency Program in Sacramento, California, and subsequently expanded to 2 other Dignity Health residency program sites. The MSH program included 3 sessions of trafficking-specific curriculum for resident physicians to prepare them to provide care for MSH patients. The current study aimed to evaluate resident physician learner confidence after participating in the MSH curriculum along with perceptions of the MSH program as a whole upon their graduation. METHODS The study was a retrospective, preassessment/postassessment design. Resident physicians completed surveys that assessed learner confidence after each of the 3 training sessions, utilizing Likert scale items. Third-year resident physicians also completed a survey that included scaled and open-ended questions. Paired t-tests were used to evaluate the data in addition to content analysis for the open-ended questions. RESULTS There were significant increases in learner confidence after the training sessions on all items measured, including identifying and caring for victims and survivors of trafficking. Third-year residents responded that the MSH program helped them to more effectively communicate and care for victims and survivors and many planned to take the trauma-informed care model to their future practices. CONCLUSION While generalizability of the study was limited due to the retrospective design, the MSH program was found to have a meaningful impact on the resident physicians who participated in the training.
Birtamimab plus standard of care in light-chain amyloidosis: the phase 3 randomized placebo-controlled VITAL trial
Authors: Gertz Morie A. , Cohen Adam D. , Comenzo Raymond L. , Kastritis Efstathios , Landau Heather J. , Libby Edward N. , Liedtke Michaela , Sanchorawala Vaishali , Schönland Stefan , Wechalekar Ashutosh , Zonder Jeffrey A. , Palladini Giovanni , Walling Jackie , Guthrie Spencer , Nie Christie , Karp Carol , Jin Yuying , Kinney Gene G. , Merlini Giampaolo 
Published: June 2023

Abstract
Amyloid light-chain (AL) amyloidosis is a rare, typically fatal disease characterized by the accumulation of misfolded immunoglobulin light chains (LCs). Birtamimab is an investigational humanized monoclonal antibody designed to neutralize toxic LC aggregates and deplete insoluble organ-deposited amyloid via macrophage-induced phagocytosis. VITAL was a phase 3 randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of birtamimab + standard of care (SOC) in 260 newly diagnosed, treatment-naive patients with AL amyloidosis. Patients received 24 mg/kg IV birtamimab + SOC or placebo + SOC every 28 days. The primary composite end point was the time to all-cause mortality (ACM) or centrally adjudicated cardiac hospitalization ≥91 days after the first study drug infusion. The trial was terminated early after an interim futility analysis; there was no significant difference in the primary composite end point (hazard ratio [HR], 0.826; 95% confidence interval [CI], 0.574-1.189; log-rank P = .303). A post hoc analysis of patients with Mayo stage IV AL amyloidosis, those at the highest risk of early mortality, showed significant improvement in the time to ACM with birtamimab at month 9 (HR, 0.413; 95% CI, 0.191-0.895; log-rank P = .021). At month 9, 74% of patients with Mayo stage IV AL amyloidosis treated with birtamimab and 49% of those given placebo survived. Overall, the rates of treatment-emergent adverse events (TEAEs) and serious TEAEs were generally similar between treatment arms. A confirmatory phase 3 randomized, double-blind, placebo-controlled clinical trial of birtamimab in patients with Mayo stage IV AL amyloidosis (AFFIRM-AL; NCT04973137) is currently enrolling. The VITAL trial was registered at www.clinicaltrials.gov as #NCT02312206.