bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor–Resistant, EGFR-Mutated Non–Small Cell Lung Cancer
Authors: Jänne Pasi A. , Baik Christina , Su Wu-Chou , Johnson Melissa L. , Hayashi Hidetoshi , Nishio Makoto , Kim Dong-Wan , Koczywas Marianna , Gold Kathryn A. , Steuer Conor E. , Murakami Haruyasu , Yang James Chih-Hsin , Kim Sang-We , Vigliotti Michele , Shi Rong , Qi Zhenhao , Qiu Yang , Zhao Lihui , Sternberg David , Yu Channing , Yu Helena A. 
Published: September 2021

Abstract

Receptor tyrosine-protein kinase ERBB3 (HER3) is expressed in most EGFR-mutated lung cancers but is not a known mechanism of resistance to EGFR inhibitors. HER3-DXd is an antibody–drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. This phase I, dose escalation/expansion study included patients with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor (TKI) therapy. Among 57 patients receiving HER3-DXd 5.6 mg/kg intravenously once every 3 weeks, the confirmed objective response rate by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1) was 39% [95% confidence interval (CI), 26.0–52.4], and median progression-free survival was 8.2 (95% CI, 4.4–8.3) months. Responses were observed in patients with known and unknown EGFR TKI resistance mechanisms. Clinical activity was observed across a broad range of HER3 membrane expression. The most common grade ≥3 treatment-emergent adverse events were hematologic toxicities. HER3-DXd has clinical activity in EGFR TKI–resistant cancers independent of resistance mechanisms, providing an approach to treat a broad range of drug-resistant cancers.

Significance:
In metastatic EGFR-mutated NSCLC, after disease progression on EGFR TKI therapy, treatment approaches include genotype-directed therapy targeting a known resistance mechanism or chemotherapy. HER3-DXd demonstrated clinical activity spanning known and unknown EGFR TKI resistance mechanisms. HER3-DXd could present a future treatment option agnostic to the EGFR TKI resistance mechanism.
See related commentary by Lim et al., p. 16.
This article is highlighted in the In This Issue feature, p. 1
Fli1 Promotes Vascular Morphogenesis by Regulating Endothelial Potential of Multipotent Myogenic Progenitors
Authors: Ferdous Anwarul , Singh Sarvjeet , Luo Yuxuan , Abedin Md. J. , Jiang Nan , Perry Cameron E. , Evers Bret M. , Gillette Thomas G. , Kyba Michael , Trojanowska Maria , Hill Joseph A. 
Published: September 2021

Rationale:
Fetal growth and survival depend critically on proper development and integrity of the vascular system. Fli1 (Friend leukemia integration 1), a member of the Ets family of transcription factors, plays critical roles in vascular morphogenesis and homeostasis at mid-gestation, the developmental stage at which expression of its upstream regulator, Etv2, ceases. However, molecular mechanisms of Fli1 action in vascular morphogenesis remain incompletely understood.

Objective:
To dissect molecular mechanisms of vascular morphogenesis governed by Fli1.

Methods and Results:

Utilizing
Fli1
promoter-driven lineage-specific
LacZ
expression, Fli1 loss-of-function strategies, and a series of molecular techniques, we demonstrate that
Fli1
expression in multipotent myogenic progenitor cells (MPCs) occurs independent of Etv2, and loss of Fli1 expression results in a significant increase in LacZ
+
cells in mesoderm within somites and limb buds, leading to reciprocal regulation of the expression of several key endothelial and myogenic genes and vascular abnormalities. Conversely, embryos harboring conditional Fli1 gain-of-function in MPCs manifested aberrant vasculogenesis with lack of myogenesis. Mechanistically, elevated Fli1 activity in myoblasts and in adult MPCs (also called satellite cells) of X-linked muscular dystrophic
mdx
mice markedly induced endothelial, but attenuated myogenic, gene expression and differentiation. Importantly, ectopic expression of Myf5 or MyoD, two key myogenic regulators, in Fli1-expressing myoblasts restored their differentiation potential, indicating that levels of Fli1 and myogenic regulators in MPCs inversely regulate their endothelial versus myogenic potential.

Conclusions:
Fli1 governs vascular morphogenesis by regulating endothelial potential by inversely regulating endothelial versus myogenic programs in MPCs. Our data uncover an important and previously unrecognized mechanism of vascular morphogenesis governed by Fli1 and highlight the physiological significance of the fine tuning of Fli1 activity in multipotent progenitors for proper vascular and muscle morphogenesis during development and disease.
The Paris Agreement as Analogy in Global Environmental Politics
Authors: Chan Nicholas 
Published: September 2021

AbstractThe Paris Agreement is increasingly being used as an analogy in global environmental politics to discuss issues beyond climate change. This Forum article explores the two main ways in which this analogy has been discursively employed: as a symbol of diplomatic success to be emulated and as a model for institutional treaty design. It illustrates the broader meanings associated with the Paris Agreement, reflecting its preeminent public and political profile among environmental issues just a few years into its history and its potential significance in shaping subsequent global environmental negotiations.
Invasive Species in Post-2020 Global Environmental Politics
Authors: Cruz Jesann Gonzalez , Johnson McKenzie F. 
Published: September 2021

Abstract
As goods and people more rapidly traverse our interconnected world, invasive alien species (IAS) are increasingly frequent, ecologically damaging, economically significant, and culturally concerning. Through examinations of IAS, global environmental politics (GEP) scholars can more deeply engage long-standing and newly emerging research problems within the three areas of global governance, global political economy, and environmental security. First, GEP scholars can use IAS research to further develop insights about the impact of problem structure on global governance. Second, examining IAS dispersal risks and associated costs, as well as intercountry variation in management responses, can generate insights about North–South power dynamics in the global political economy and how distributive conflict is likely to shape future invasion risk. Third, notions of environmental security in GEP scholarship can be challenged and further developed by examining the conceptualization and operationalization of “biosecurity” amid increasingly diverse multispecies assemblages. Greater research attention to IAS in GEP is long overdue, and we intend for this article to open novel pathways for GEP interdisciplinary research on IAS.
Do Infants Really Learn Phonetic Categories?
Authors: Feldman Naomi H. , Goldwater Sharon , Dupoux Emmanuel , Schatz Thomas 
Published: September 2021

AbstractEarly changes in infants’ ability to perceive native and nonnative speech sound contrasts are typically attributed to their developing knowledge of phonetic categories. We critically examine this hypothesis and argue that there is little direct evidence of category knowledge in infancy. We then propose an alternative account in which infants’ perception changes because they are learning a perceptual space that is appropriate to represent speech, without yet carving up that space into phonetic categories. If correct, this new account has substantial implications for understanding early language development.
Introducing and Evaluating the Climate Hazards Center IMERG with Stations (CHIMES): Timely Station-Enhanced Integrated Multisatellite Retrievals for Global Precipitation Measurement
Authors: Funk Chris C. , Peterson Pete , Huffman George J. , Landsfeld Martin Francis , Peters-Lidard Christa , Davenport Frank , Shukla Shraddhanand , Peterson Seth , Pedreros Diego H. , Ruane Alex C. , Mutter Carolyn , Turner Will , Harrison Laura , Sonnier Austin , Way-Henthorne Juliet , Husak Gregory J. 
Published: September 2021

Abstract
As human exposure to hydroclimatic extremes increase and the number of in situ precipitation observations declines, precipitation estimates, such as those provided by the Integrated Multisatellite Retrievals for Global Precipitation Measurement (GPM) (IMERG) mission, provide a critical source of information. Here, we present a new gauge-enhanced dataset [the Climate Hazards Center IMERG with Stations (CHIMES)] designed to support global crop and hydrologic modeling and monitoring. CHIMES enhances the IMERG Late Run product using an updated Climate Hazards Center (CHC) high-resolution climatology (CHPclim) and low-latency rain gauge observations. CHPclim differs from other products because it incorporates long-term averages of satellite precipitation, which increases CHPclim’s fidelity in data-sparse areas with complex terrain. This fidelity translates into performance increases in unbiased IMERGlate data, which we refer to as CHIME. This is augmented with gauge observations to produce CHIMES. The CHC’s curated rain gauge archive contains valuable contributions from many countries. There are two versions of CHIMES: preliminary and final. The final product has more copious and better-curated station data. Every pentad and month, bias-adjusted IMERGlate fields are combined with gauge observations to create pentadal and monthly CHIMESprelim and CHIMESfinal. Comparisons with pentadal, high-quality gridded station data show that IMERGlate performs well (r = 0.75), but has some systematic biases which can be reduced. Monthly cross-validation results indicate that unbiasing increases the variance explained from 50% to 63% and decreases the mean absolute error from 48 to 39 mm month−1. Gauge enhancement then increases the variance explained to 75%, reducing the mean absolute error to 27 mm month−1.
Evaluation of the Performance of CMIP5 and CMIP6 Models in Simulating the Victoria Mode–El Niño Relationship
Authors: Wang Zhenchao , Han Lin , Zheng Jiayu , Ding Ruiqiang , Li Jianping , Hou Zhaolu , Chao Jinghua 
Published: September 2021

AbstractThe Victoria mode (VM) is the second dominant sea surface temperature mode in the North Pacific, forced by North Pacific Oscillation–like extratropical atmospheric variability. Observational studies have shown that the boreal spring VM is closely connected to the following winter El Niño, with the VM efficiently acting as a precursor signal to El Niño events. This study evaluates the relationship of the spring VM with subsequent winter El Niño in the preindustrial simulations of phases 5 and 6 of the Coupled Model Intercomparison Project (CMIP5 and CMIP6). We found that most CMIP5 and CMIP6 models can simulate the basic characteristics of the VM reasonably well. The current CMIP6 models simulate the VM–El Niño connections more realistically as compared to the earlier CMIP5 models. The analysis further suggests that the improved capability of the CMIP6 models to simulate the VM–El Niño relationship is because the CMIP6 models are better able to capture the VM-related surface air–sea thermodynamic coupling process over the subtropical/tropical Pacific and the seasonal evolution of VM-related anomalous subsurface ocean temperature in the equatorial Pacific.
Acceptance of COVID-19 Vaccine Among Refugees in the United States
Authors: Zhang Mengxi , Gurung Ashok , Anglewicz Philip , Subedi Parangkush , Payton Colleen , Ali Ahmed , Ibrahim Anisa , Haider Mahri , Hamidi Navid , Atem Jacob , Thang Jenni , Wang Siqin , Kim Curi , Kimball Sarah L. , Karaki Fatima , Nazhat Najib , Abouagila Mouammar , Yun Katherine 
Published: September 2021

Objective Little is known about COVID-19 vaccination intentions among refugee communities in the United States. The objective of this study was to measure COVID-19 vaccination intentions among a sample of refugees in the United States and the reasons for their vaccine acceptance or hesitancy. Methods From December 2020 through January 2021, we emailed or text messaged anonymous online surveys to 12 bilingual leaders in the Afghan, Bhutanese, Somali, South Sudanese, and Burmese refugee communities in the United States. We asked community leaders to complete the survey and share the link with community members who met the inclusion criteria (arrived in the United States as refugees, were aged ≥18, and currently lived in the United States). We compared the characteristics of respondents who intended to receive the COVID-19 vaccine with those of respondents who did not intend to receive the vaccine or were unsure. We then conducted crude and adjusted logistic regression analysis to measure the association between employment as an essential worker and COVID-19 vaccine acceptance. Results Of 435 respondents, 306 (70.3%) indicated that they planned to receive a COVID-19 vaccine. Being an essential worker (adjusted odds ratio [aOR] = 2.37; 95% CI, 1.44-3.90) and male sex (aOR = 1.87; 95% CI, 1.12-3.12) were significantly associated with higher odds of intending to receive a COVID-19 vaccine. Among respondents who intended to receive a COVID-19 vaccine, wanting to protect themselves (68.6%), family members (65.0%), and other people (54.3%) were the main reasons. Conclusion Many refugees who responded to the survey, especially those who worked in essential industries, intended to receive a COVID-19 vaccine. Community organizations, health care providers, and public health agencies should work together to ensure that vaccine registration and vaccination sites are accessible to refugees.
Assessment of One Health Knowledge, Animal Welfare Implications, and Emergency Preparedness Considerations for Effective Public Health Response
Authors: Pimentel Linda C. , May Alicia C. , Iskander John K. , Banks Ronald E. , Gibbins John D. 
Published: September 2021

Objectives Information on knowledge of public health professionals about health aspects of the human–animal interface, referred to as One Health, is limited. The objective of this study was to identify factors associated with animal welfare attitudes, practices, and One Health awareness among US Public Health Service (USPHS) officers to assess preparedness for public health response. Methods USPHS officers participated in an online, self-administered survey from February 15 through March 2, 2018. A total of 1133 of 6474 (17.5%) USPHS officers responded. We collected information on officers’ demographic characteristics, animal welfare attitudes and practices, volunteer and work exposure to animals, and One Health knowledge. We compared (1) One Health knowledge and animal work exposure (deployment, regular assignment, or none) and (2) animal welfare importance and animal work exposure. To adjust for demographic characteristics associated with One Health knowledge, we used multivariable logistic regression. Results One-third of nonveterinary officers reported encountering animals during deployment, and 65% reported that animal welfare was very or extremely important. We found no difference in One Health knowledge between nonveterinary officers who participated in deployments involving animals and nonveterinary officers who had no work exposure to animals (adjusted odds ratio [aOR] = 1.11; 95% CI, 0.71-1.75). Nonveterinary officers who participated in animal-related public health activities during regular assignment were more likely to have One Health knowledge than nonveterinary officers who had no work exposure to animals (aOR = 7.88; 95% CI, 5.36-11.59). Conclusions One Health knowledge and awareness should be further explored in the current US public health workforce to identify training needs for emergency preparedness and other collaborative opportunities.
Price Transparency and Compliance With Federal Regulation for Pediatric Tonsillectomy
Authors: Ayoub Noel Fahed , Balakrishnan Karthik 
Published: September 2021

ObjectiveTo improve hospital price transparency, the Centers for Medicare & Medicaid Services (CMS) requires, as of January 2021, that all hospitals reveal charges for specific items and services. This analysis investigates whether otolaryngology residency–affiliated hospitals have complied with this new regulation, and it evaluates the variability in hospital‐reported charges for pediatric tonsillectomy.Study DesignCross‐sectional analysis.SettingsSubset of hospitals affiliated with otolaryngology residency programs.MethodsHospital websites were searched to determine compliance rates with CMS guidelines by posting a price transparency tool and specific charges for Current Procedural Terminology code 42820 (tonsillectomy and adenoidectomy, <12 years old). Various charges were collected: gross charge, discounted cash price, deidentified minimum and maximum negotiated charges, hospital fees, and physician fees.ResultsOverall 104 unique hospitals were analyzed: 81 (78%) provided pricing data, but only 28 (27%) complied with CMS guidelines. The median reported total gross charge was $13,239 (range, $600‐$41,957); deidentified minimum negotiated charge, $9222 (range, $337‐$25,164); and deidentified maximum negotiated charge, $17,355 (range, $1002‐$54,987). Hospital fees (median, $11,900; range, $2304‐$38,831) were consistently higher than physician fees (median, $1827; range, $420‐$5063). All estimates included a disclaimer stating that values likely underrepresent true prices.ConclusionHospital compliance with the new regulation remains low, which limits efforts toward improved price transparency. There is wide variability in reported charges for pediatric tonsillectomy and adenoidectomy.
Technology-Based Interventions to Improve Help-Seeking for Mental Health Concerns: A Systematic Review
Authors: Johnson Jemimah A. , Sanghvi Prachi , Mehrotra Seema 
Published: September 2021

Background: Despite the high prevalence of mental health disorders worldwide, a significant proportion of distressed individuals do not seek professional help. Digital technology can be a potential bridge to reduce the treatment gap for mental disorders. A systematic review was undertaken to examine the technology-based interventions aimed at improving help-seeking attitude, intention, or behavior for mental health concerns. Methods: The literature search was conducted in January–February 2020 through various e-databases using relevant keywords that targeted help-seeking interventions for mental health disorders via different technology modes. Results: 21 studies (15 randomized controlled trials and six non-randomized studies) were reviewed. The included studies were published between April 2006 to February 2020. Majority of the interventions led to an increase in the help-seeking variables. The crucial role of online delivery, participant involvement, and embedded links to professional services in encouraging help-seeking is highlighted. The review emphasizes the need for understanding utility of multicomponent interventions with personalized elements targeting help-seeking behavior, particularly in low-middle-income countries, and studies involving longer duration follow-ups. Conclusion: This systematic review is the first of its kind to examine technology-based interventions to improve help-seeking for mental health and suggests that such interventions play a crucial role in positively impacting help-seeking. The complex interplay between the relevant variables such as mental health literacy, stigma, help-seeking attitude, intention and behavior, and the intervention components that may have a differential bearing on these variables are issues that merit urgent attention in further research.
Anesthetic choice for arteriovenous access creation: A National Anesthesia Clinical Outcomes Registry analysis
Authors: Woods Kaitlin , Minc Samantha D , Thibault Dylan , Lambert Jacob , Jalil Amaris , Marone Luke , Ellison Matthew , Hayanga JW Awori , Hayanga Heather K 
Published: September 2021

Background: We sought to evaluate differences in primary anesthetic type used in arteriovenous access creation with the hypothesis that administration of regional anesthesia and monitored anesthesia care (MAC) with local anesthesia as the primary anesthetic has increased over time. Methods: National Anesthesia Clinical Outcomes Registry data were retrospectively evaluated. Covariates were selected a priori within multivariate models to determine predictors of anesthetic type in adults who underwent elective arteriovenous access creation between 2010 and 2018. Results: A total of 144,392 patients met criteria; 90,741 (62.8%) received general anesthesia. The use of regional anesthesia and MAC decreased over time (8.0%–6.8%, 36.8%–27.8%, respectively; both p < 0.0001). Patients who underwent regional anesthesia were more likely to have ASA physical status >III and to reside in rural areas (52.3% and 12.9%, respectively; both p < 0.0001). Patients who underwent MAC were more likely to be older, male, receive care outside the South, and reside in urban areas (median age 65, 56.8%, 68.1%, and 70.8%, respectively; all p < 0.0001). Multivariate analysis revealed that being male, having an ASA physical status >III, and each 5-year increase in age resulted in increased odds of receiving alternatives to general anesthesia (regional anesthesia adjusted odds ratios (AORs) 1.06, 1.12, and 1.26, MAC AORs 1.09, 1.2, and 1.1, respectively; all p < 0.0001). Treatment in the Midwest, South, or West was associated with decreased odds of receiving alternatives to general anesthesia compared to the Northeast (regional anesthesia AORs 0.28, 0.38, and 0.03, all p < 0.0001; MAC 0.76, 0.13, and 0.43, respectively; all p < 0.05). Conclusions: Use of regional anesthesia and MAC with local anesthesia for arteriovenous access creation has decreased over time with general anesthesia remaining the primary anesthetic type. Anesthetic choice, however, varies with patient characteristics and geography.
Changes in pediatric major trauma epidemiology, injury patterns, and outcome during COVID-19–associated lockdown
Authors: Pines Naama , Bala Miklosh , Gross Itai , Ohana-Sarna-Cahan Lea , Shpigel Ruth , Nama Ahmad , Asaf Kedar , Rosenberg Bsc Moriah P , Hashavya Saar 
Published: September 2021

Introduction The COVID-19 pandemic and its associated preventive measures such as national and regional lockdowns have dramatically changed the epidemiology of pediatric admissions to the emergency department. Nevertheless, there are scant data on the epidemiology and injury patterns of major pediatric trauma injuries during these lockdown periods. Methods A single-center retrospective study of data obtained from a tertiary level 1 trauma hospital trauma registry. The data included demographics, injury mechanisms, injury severity and type, treatment, and resource utilization in children aged 0–18 years who required trauma team activation upon arrival. The analysis compares the data from the 5-week lockdown period from March to May 2020 in Jerusalem, Israel, to its parallel periods in 2018–2019. Results A total of 187 trauma visits that required trauma team activation (TTA) were analyzed: 48 visits during the lockdown period vs. 139 in 2018–2019, corresponding to a 40% drop in TTA. There was a significant decrease of 34% in MVA-related injuries ( p = 0.0001) but a significant increase of 14% in burns ( p = 0.01) and a 16% increase in bicycle-related injuries ( p = 0.001). No changes in ISS, injury patterns, admission rate, PICU utilization, or need for interventions were observed. Conclusion There was a significant decrease in the number of overall pediatric trauma visits during the 2020 lockdown, mainly in MVA-associated trauma, but an increase in burns and bicycle injuries. These findings can thus inform policy makers as to the need to formulate prevention awareness programs alerting the public to indoor hazards and the dangers of activities outside the home. Furthermore, it can inform hospital policy decision-making in future lockdowns. The fact that PICU admissions and the need for operating rooms stayed unchanged suggests that it is vital to maintain trauma team capabilities even during lockdowns.