bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma
Authors: Saliby Renee Maria , El Zarif Talal , Bakouny Ziad , Shah Valisha , Xie Wanling , Flippot Ronan , Denize Thomas , Kane M. Harry , Madsen Katrine N. , Ficial Miriam , Hirsch Laure , Wei Xiao X. , Steinharter John A. , Harshman Lauren C. , Vaishampayan Ulka N. , Severgnini Mariano , McDermott David F. , Lee Gwo-Shu Mary , Xu Wenxin , Van Allen Eliezer M. , McGregor Bradley A. , Signoretti Sabina , Choueiri Toni K. , McKay Rana R. , Braun David A. 
Published: June 2023

Abstract
Renal cell carcinoma (RCC) of variant histology comprises approximately 20% of kidney cancer diagnoses, yet the optimal therapy for these patients and the factors that impact immunotherapy response remain largely unknown. To better understand the determinants of immunotherapy response in this population, we characterized blood- and tissue-based immune markers for patients with variant histology RCC, or any RCC histology with sarcomatoid differentiation, enrolled in a phase II clinical trial of atezolizumab and bevacizumab. Baseline circulating (plasma) inflammatory cytokines were highly correlated with one another, forming an “inflammatory module” that was increased in International Metastatic RCC Database Consortium poor-risk patients and was associated with worse progression-free survival (PFS; P = 0.028). At baseline, an elevated circulating vascular endothelial growth factor A (VEGF-A) level was associated with a lack of response (P = 0.03) and worse PFS (P = 0.021). However, a larger increase in on-treatment levels of circulating VEGF-A was associated with clinical benefit (P = 0.01) and improved overall survival (P = 0.0058). Among peripheral immune cell populations, an on-treatment decrease in circulating PD-L1+ T cells was associated with improved outcomes, with a reduction in CD4+PD-L1+ [HR, 0.62; 95% confidence interval (CI), 0.49–0.91; P = 0.016] and CD8+PD-L1+ T cells (HR, 0.59; 95% CI, 0.39–0.87; P = 0.009) correlated with improved PFS. Within the tumor itself, a higher percentage of terminally exhausted (PD-1+ and either TIM-3+ or LAG-3+) CD8+ T cells was associated with worse PFS (P = 0.028). Overall, these findings support the value of tumor and blood-based immune assessments in determining therapeutic benefit for patients with RCC receiving atezolizumab plus bevacizumab and provide a foundation for future biomarker studies for patients with variant histology RCC receiving immunotherapy-based combinations.
Indagando as aparências, apontando as evidências: resquícios da cultura caipira no hit de Chitãozinho & Xororó
Authors: Santos Julio César Ribeiro dos 
Published: June 2023

Parto da canção romântico-popular “Evidências” (Augusto; Valle, 1990) e suas traduções por Chitãozinho & Xororó nos álbuns Caubóis do Asfalto (1990), Elas em evidências (2015) e como tema de encerramento da turnê Evidências (2016-2020) no intento de investigar os refluxos e recrudescimentos do povo caipira naquilo que se chama canção sertaneja no âmbito da Indústria Cultural. Sirvo-me de alguns elementos teoria da linguagem proposta por Henri Meschonnic (2006; 2008; 2015) para elucidar a compreensão da maneira como afeto e conceito em um só bocado de palavra agem e transformam os modos de ver, de ouvir e sentir (Meschonnic 2015: 9). Índices como tonalidade anasalada, extensão de tessitura, falsetes, dupla melodia principal, alguma arrogância e idealização afetiva, presentes em Caubóis do asfalto (1990), revigoram via intertextualidade o povo caipira da Paulistânia (RIBEIRO, 1995), trazendo os brãos da roça (Corrêa 2014) e o sertanejo (Lima 1972) onde inicialmente havia pop; em Elas em evidências (2015), há deslocamentos dados, sobretudo, pelo acréscimo das diferentes formas de empoderamento feminino por distintas oralidades (Meschonnic 2006) numa importante articulação que atende ao escopo (Veermer 1996 apud Pyn 2017) dos interesses de mercado. Já como tema de encerramento (Paladini 2015), emerge como virtuose o rock progressivo superando as expectativas do receptor e deslocando os limites das ordens do discurso.
Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms
Authors: Wang Xin , Khurshid Shaan , Choi Seung Hoan , Friedman Samuel , Weng Lu-Chen , Reeder Christopher , Pirruccello James P. , Singh Pulkit , Lau Emily S. , Venn Rachael , Diamant Nate , Di Achille Paolo , Philippakis Anthony , Anderson Christopher D. , Ho Jennifer E. , Ellinor Patrick T. , Batra Puneet , Lubitz Steven A. 
Published: June 2023

BACKGROUND:
Artificial intelligence (AI) models applied to 12-lead ECG waveforms can predict atrial fibrillation (AF), a heritable and morbid arrhythmia. However, the factors forming the basis of risk predictions from AI models are usually not well understood. We hypothesized that there might be a genetic basis for an AI algorithm for predicting the 5-year risk of new-onset AF using 12-lead ECGs (ECG-AI)-based risk estimates.

METHODS:
We applied a validated ECG-AI model for predicting incident AF to ECGs from 39 986 UK Biobank participants without AF. We then performed a genome-wide association study (GWAS) of the predicted AF risk and compared it with an AF GWAS and a GWAS of risk estimates from a clinical variable model.

RESULTS:

In the ECG-AI GWAS, we identified 3 signals (
P
<5×10
−8
) at established AF susceptibility loci marked by the sarcomeric gene
TTN
and sodium channel genes
SCN5A
and
SCN10A
. We also identified 2 novel loci near the genes
VGLL2
and
EXT1
. In contrast, the clinical variable model prediction GWAS indicated a different genetic profile. In genetic correlation analysis, the prediction from the ECG-AI model was estimated to have a higher correlation with AF than that from the clinical variable model.

CONCLUSIONS:
Predicted AF risk from an ECG-AI model is influenced by genetic variation implicating sarcomeric, ion channel and body height pathways. ECG-AI models may identify individuals at risk for disease via specific biological pathways.
Development and Impact of an Intercultural STEAM Program on Science Classroom Creativity
Authors: Kim Ei Seul , Chu Hye-eun , Song Jinwoong 
Published: June 2023

Abstract
As collaboration among scientists from diverse backgrounds can help generate theories and foster the discovery of natural phenomena, the importance of creativity via collaboration in science learning has been widely recognized. This study aimed to investigate the science classroom creativity of Korean high school students who participated in an Australia-Korea intercultural STEAM program (ISP). Due to COVID-19 restrictions, data was only collected from Korean students. The Revised Science Classroom Creativity Questionnaire (R-SCCQ) was administered to 25 Korean students, and interviews were conducted with 10 students to explore creative behavior. The results showed a significant increase in students’ science classroom creativity following their participation in the ISP. This study shows that the intercultural experience provided by the program can help induce a more flexible mindset and encourage different perspectives, ultimately enhancing science classroom creativity. This finding is significant as it highlights the potential of the ISP as a new teaching method for promoting creativity in science education.
Using an Artificial Intelligence Chatbot in Scientific Inquiry: Focusing on a Guided-Inquiry Activity Using Inquirybot
Authors: Chang Jina , Park Joonhyeong , Park Jisun 
Published: June 2023

Abstract
This study aims to explore how to use an AI chatbot pedagogically in scientific inquiry by developing a guided-inquiry activity using an AI chatbot and applying it. The developed guided-inquiry activity consisted of designing and doing inquiry activities using the transmission of sound as the topic. In this activity, a chatbot, which was given the name Inquirybot, was designed with conversation flow and scripts for guiding the inquiry design process. By applying the developed inquiry activities and Inquirybot to fifth- and sixth-grade gifted students, we found several practical possibilities and challenges for using an AI chatbot in scientific inquiry. Based on the results, future tasks and educational implications are discussed in terms of efficiently adapting AI chatbots in scientific-inquiry activities.
Opposite Changes in Monsoon Precipitation and Low Pressure System Frequency in Response to Orographic Forcing
Authors: Thomas Tresa Mary , Bala Govindasamy , Vemavarapu Srinivas Venkata , Boos William R. 
Published: June 2023

Abstract
Monsoon low pressure systems (LPS) are synoptic-scale disturbances that form along the quasi-stationary trough of the larger-scale South Asian summer monsoon, producing a large fraction of total monsoon precipitation. Here, we use an Earth system model to investigate the influence of Tibetan and Himalayan orography (THO) on mean monsoon strength and LPS activity. The influence of THO height on LPS activity has not been investigated before. The model simulates decreased mean monsoon circulation and precipitation when THO is removed, but the number of LPS and the meridional extent of LPS activity increase; this is an unexpected, important finding given that LPS are principal rain-bearing systems of the monsoon. The decreased mean monsoon circulation and precipitation on removal of THO are attributed to enhanced mixing of dry extratropical air into the humid monsoon domain, as demonstrated by prior studies. The increase in LPS frequency and the meridional extent of LPS activity is attributed to the increase in magnitude and meridional extent of the low-level meridional shear of zonal wind, which previous work showed amplifies LPS through barotropic growth. Specifically, as monsoon precipitation decreases, the sensible heat-driven low-level trough intensifies and shifts equatorward; this strengthens the shear zone in which LPS grow. Conversely, increasing THO height decreases the magnitude and meridional extent of cyclonic shear over India, decreasing LPS frequency and the spatial extent of LPS activity while increasing total monsoon precipitation. These results demonstrate that LPS activity and total monsoon rainfall can undergo large, opposing changes in response to imposed forcings.

Significance Statement
Monsoon low pressure systems (LPS) are propagating atmospheric vortices that deliver a large fraction of seasonal-mean precipitation to agricultural regions of India. The influence of Tibetan and Himalayan orography (THO) on the South Asian monsoon is an active area of research, but its effect on LPS has remained unexplored. Here, a global climate model is used to simulate LPS characteristics for different heights of THO. Flattening the THO reduces total summer monsoon precipitation but increases the number of LPS and the spatial extent of LPS activity. We attribute these LPS changes to a decrease in the magnitude and meridional extent of the hydrodynamically unstable low-level cyclonic shear zone over South Asia that occurs when orography is flattened.
Response of the Snowball Earth Climate to Orbital Forcing at a High CO2 Level
Authors: Wu Jiacheng , Liu Yonggang 
Published: June 2023

Abstract
How the climate responded to orbital forcing during the Neoproterozoic snowball Earth events, the most extreme glaciations on Earth, is still unclear. Here, we investigate this problem using a climate model. To simplify the analysis, continents are removed. The results show that even in this simplified situation, the snowball Earth climate is sensitive to orbital configurations. The globally averaged annual surface temperature can differ by 2.4°C, and the maximum monthly mean temperature can differ by 3.7°C under different orbital configurations. Therefore, a snowball Earth could be deglaciated more easily in some orbital configurations than in others. The climatic effect of a particular orbital parameter is highly dependent on the values of other parameters. For example, the effect of obliquity on tropical surface temperature is generally small (<1°C), but it can become large (3.8°C) when eccentricity is large and the northern autumn occurs at perihelion (precession = 180°). Surprisingly, the global temperature is generally lower at high eccentricity than at near-zero eccentricity, even though the total insolation received by Earth is higher in the former than in the latter. Moreover, we find that the Milankovitch hypothesis is valid not only in the extratropical region, but also in the tropics; the snow thickness in the tropical region is inversely proportional to the maximum monthly insolation received in this region.
Hypothyroidism Complicated by Vitamin C and Thiamin Deficiency in Surgical Patients
Authors: Bonatti Hugo J. R. , Gona Sridhar Rao , Feaga Catherine , George Aaron E. 
Published: June 2023

Multiple vitamin deficiencies together with endocrinopathy may be encountered in individuals presenting with critical illness. Following the surprise postmortem diagnosis of concomitant scurvy, Wernicke, and hypothyroidism in an elderly woman presenting with a mix of atypical symptoms, patients considered at risk were tested for TSH, vitamin C, and thiamin levels. Between September 1, 2018, and December 31, 2022, 801 vitamin C levels in 679 patients were measured in our rural hospital and 309 (39%) were found <0.4 mg/dL. In this population, 39% of 626 thiamin levels were found to be low. Twenty-two patients with vitamin C and/or thiamin deficiency and elevated TSH levels were identified. Two patients died from scurvy; one also had myxedema. The incidence of vitamin C and thiamin deficiency in our patient population was higher than expected. Further studies should determine if this is unique to our rural setting or part of a bigger trend associated with poor dietary choices.
Learning Curves in Establishing a New Minimally Invasive Pancreas Program
Authors: Park Joon Y. , Mirzaie Sarah , Premji Aly , Seo Youngji , Mederos Michael , Hines Joe , Donahue Timothy , Tomlinson James , King Jonathan , Girgis Mark 
Published: June 2023

Introduction Robotic pancreaticoduodenectomy (rPD) is a complex operation with a reported learning curve of 80 cases. Two recent graduates of a formal robotic complex general surgical oncology training program have been performing rPD at our institution since 2016, which had no previous institutional experience with rPD. Objective To evaluate the learning curve associated with developing a new robotic pancreaticoduodenectomy (rPD) program by fellowship trained surgeons with institutional support. Methods Sixty patients undergoing rPD from 2016 to 2022 were reviewed for and compared with proficiency benchmarks set by the University of Pittsburg experience. Results By 30 cases, operative time met the proficiency benchmark of 391 minutes. Additionally, the entire cohort had comparable rates of clinically relevant postoperative pancreatic fistula (6.7% vs 3%, P = .6), 30-day mortality (0% vs 3%, P = .18), major complications (Clavien >2; 23% vs 17%, P = .14), and length of stay (6 vs 7 days, P = .49) when compared to the benchmark. Conclusion Perioperative outcomes were comparable to proficiency benchmarks from initiation of the new rPD program, and operative time reached proficiency benchmark by 30 cases. This data suggests that graduates of formal rPD training programs can safely establish new minimally invasive pancreas programs at sites with no previous institutional rPD experience.
Prospective Assessment of Social Determinants of Health and Length of Stay Among Emergency General Surgery and Trauma Patients
Authors: DePolo Nicole , Bathan Karen , Tran Zachary , Peng Jiahao , Singh Pramil , Lum Sharon S. , Wu Esther 
Published: June 2023

Background Social determinants of health (SDOH) including insurance and substance use affect 50-90% of health outcomes, yet there remains no standard means to quantify or predict their impact. We prospectively evaluated the effects of SDOH on length of stay (LOS) and readmissions among emergency general surgery (EGS) and trauma patients. We compared these outcomes with Medicare Diagnosis Related Group (DRG) data to better quantify the impact of SDOH. Methods Adult (≥18 years old) EGS/trauma patients admitted July 7-28, 2020 at a Level 1 trauma center were prospectively enrolled. Primary outcomes were overall LOS, one-year readmissions, and excess LOS (eLOS), defined as days beyond DRG mean LOS. Results Assessment of SDOH among the 52 patients enrolled revealed that 5.8% of patients were homeless; 26.9% experienced substance abuse; 13.5% were uninsured on admission; and 7.7% on discharge. Mean LOS was 5 ± 4 days; 1-year readmission rate 25.0%; eLOS mean 1.75 ± 2.4 days. LOS was associated with substance use (OR 70.6 95% CI 11.7-160.4). eLOS was associated with substance use (OR 6.1, 95% CI 1.5-25.1) and public or no insurance (OR 26.0, 95% CI 4.9-138.1). No correlations were found between SDOH and readmission rates. Discussion EGS and trauma patients experience high rates of negative SDOH which affect clinical outcomes including LOS and readmissions. Medicare DRG determined eLOS is a fiscally relevant measure of the impact of SDOH and differs from LOS and readmissions. Further investigation is required to determine if eLOS can delineate the effects of other SDOH on admission outcomes for this patient population.
Assessment of cardiac load-responsiveness in veno-arterial extracorporeal life support: A case series
Authors: Cornelisse Y , Weerwind PW , Bol ME , Simons AP 
Published: June 2023

Introduction Well-timed explant of veno-arterial extracorporeal life support (V-A ECLS) depends on adequate assessment of cardiac recovery. Often, evaluation of cardiac recovery consists of reducing support flow while visualizing cardiac response using transoesophageal echocardiography (TEE). This method, however, is time consuming and based on subjective findings. The dynamic filling index (DFI) may aid in the quantitative assessment of cardiac load-responsiveness. The dynamic filling index is based on the relationship of support flow and pump speed, which varies with varying hemodynamic conditions. This case series intends to investigate whether the DFI may support TEE in facilitating the assessment of cardiac load-responsiveness. Methods Measurements for DFI-determination were performed in seven patients while simultaneously assessing ventricular function by measuring the aortic velocity time integral (VTI) using TEE. Measurements consisted of multiple consecutive transient speed manipulations (∼100 r/min) during weaning trials, both at full support and during cardiac reloading at reduced support. Results The VTI increased between full and reduced support in six weaning trials. In five of these trials DFI decreased or remained equal, and in one case DFI increased. Of the three trials in which VTI decreased between full and reduced support, DFI increased in two cases and decreased in one case. Changes in DFI, however, are mostly smaller than the detection threshold of 0.4 mL/rotation. Conclusion Even though current level of accuracy of the parameter requires further investigation to increase reliability and possibly predictability, DFI seems likely to be a potential parameter in supporting TEE for the assessment of cardiac load-responsiveness.
Mapping Publication Status and Exploring Hotspots in a Research Field: Breastfeeding
Authors: Sabancı Baransel Esra , Uçar Tuba , Çelik Osman Tayyar 
Published: June 2023

Background: Breastfeeding has been the subject of scientific studies for many years. Identifying the current trends and hotspots in breastfeeding research can further advance understanding in the field. Research Aim: This study aimed to review the basic and conceptual structure of the literature on breastfeeding from a macro perspective. Methods: The dataset for this study included 8,509 articles published between 1980 and 2022 accessed through the Web of Science database. Bibliometric methods were used to assess the growth direction of the literature on breastfeeding, the publication performance by country, influential journals and articles, co-citation networks, and keywords. Results: Research on breastfeeding developed slowly until the 2000s, at which point the speed of growth increased. The United States was the country in which most of the breastfeeding research was produced as well as being at the center of international collaborative networks. An examination of author productivity established that there was no specialization in breastfeeding. The results of citation and keyword analyses demonstrated that the literature on breastfeeding is sensitive to current developments, and the psychological aspects of breastfeeding have been intensively discussed, especially in recent years. Moreover, our results demonstrate that breastfeeding support programs are a distinct area if interest. Despite the abundance of research available, more studies are needed for specialization in this field. Conclusion: This broad overview of the field of breastfeeding research can inform the direction and advancement of the literature.
Sexual and reproductive health needs of young women living with perinatally acquired HIV
Authors: Nott Veronica R , Hazell George A , Ayres Sara , Kirkhope Natalie , Fidler Sarah , Foster Caroline 
Published: June 2023

Background Increasingly, young women living with perinatally acquired HIV (YWLPaHIV) have transitioned from paediatric to adult services. There remains a paucity of data on the sexual and reproductive health (SRH) needs of YWLPaHIV and their access to youth-friendly care. Amidst healthcare changes due to COVID-19 pandemic restrictions, we explored SRH needs of a cohort of YWLPaHIV. Methods Evaluation of SRH needs of YWLPaHIV attending a UK NHS-youth HIV service with data collected from patient records and self-reported questionnaires amongst women attending between July and November 2020 following easing of the first lockdown and reintroduction of in-person appointments. Results 71 of 112 YWLPaHIV registered at the clinic completed questionnaires during the study period and were included in the analysis. Median age was 23 y (IQR 21–27, range 18–36). 51/71(72%) reported coitarche, average age 17.6 y (IQR 16–18, range 14–24). 24 women reported 47 pregnancies resulting in 16 (34%) HIV-negative live-births, 19 (40%) terminations, 9(19%) miscarriages, with 3 pregnancies ongoing. 31/48(65%) sexually active women reported current contraception: 10 (32%) condoms, 19 (62%) long-acting, and 3(10%) oral contraceptive pill. 18/51(35%) reported a previous sexually transmitted infection; human papillomavirus (HPV) (11), Chlamydia trachomatis (9) and herpes simplex (2). 27/71(38%) women had undergone cervical cytology including 20/28(71%) women aged ≥25 y with abnormalities documented in 29%. HPV vaccination was reported in 83%, with protective hepatitis B titres in 71%. Conclusion High rates of unplanned pregnancy, STIs and cervical abnormalities highlight the continuing SRH needs of YWLPaHIV and requirement for open access to integrated HIV/SRH services despite pandemic restrictions.