bluuebunny/crossref_metadata_2025_split huggingface dataset:
KRAS mutation subtypes responded differently to combination immunotherapy via disturbing myeloid-derived suppressor cells in non-small cell lung cancer.
Authors: Gong Caifeng , Yang Xu , Zhang Jinsong , Wan Rui , Zhong Jia , Wang Zhijie , Wang Jie 
Published: June 2024

8635 Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has shown high efficacy in non-small cell lung cancer (NSCLC) patients, but further exploration of the predictive biomarkers is needed. KRAS is the most common driver oncogene in patients with NSCLC. However, the influence of different KRAS mutation subtypes on immunotherapy response remains controversial. We aimed to evaluate the value of KRAS mutation subtypes for predicting response to immunotherapy in NSCLC patients and to further analyze the related tumor immune microenvironment (TiME) phenotypes. Methods: In this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICIs and whose available molecular analysis included KRAS mutation information between January 2017 and December 2022. NSCLC tissue samples were collected for TiME analysis. Differences in immune cell subsets between different groups were analyzed using the Mann‒Whitney U test. Clinical characteristics, ICI treatment efficacy, progression-free survival (PFS), and overall survival (OS) were analyzed using multivariate Cox models. Results: A total of 1913 eligible KRAS-mutated NSCLC patients were screened, and 137 patients who received systemic immunotherapy were enrolled (108 males vs 29 females), with a median age of 62 (range, 39-84) years. Among them, 126 (92.0%) patients had adenocarcinoma, 99 (72.3%) patients were systemic therapy naïve, and 124 (90.5%) patients received combined immunotherapy. Among the patients with KRAS mutations, 48 (35.0%) had G12C, 20 (14.6%) had G12V, 27 (19.7%) had G12D and 42 (30.7%) had other subtypes. PFS was significantly longer in the G12C subgroup than in the other mutation subgroup (median PFS: 11.3 vs 6.8 months, P = 0.001). The median PFS times in the G12C/G12V subgroup and the other groups were 11.1 months and 6.5 months, respectively ( P= 0.0005). Multivariate analysis of the immunotherapy cohort revealed that G12C/G12V was an independent predictor of PFS ( P = 0.003, hazard ratio (HR): 2.021, 95% CI: 1.265-3.227). Further TiME analysis suggested that the infiltration of myeloid-derived suppressor cells (MDSCs, CD33+CD11b+) in the tumor and stromal areas in the G12C/G12V subgroup was significantly lower than that in the other subgroup (tumor area, P= 0.045; stroma area, P= 0.015). However, no significant difference in PD-L1 expression was found between the G12C/G12V group and the other groups. Conclusions: KRAS G12C and G12V were associated with favorable combined ICI treatment efficacy in patients with NSCLC. Patients with G12C or G12V mutations had longer PFS and lower infiltration of MDSCs. KRAS mutation subtypes are potential predictive biomarkers disturbed by MDSCs for combination therapy in NSCLC patients.
Loss of heterozygosity (LOH) in KEAP1/STK11-mutated lung adenocarcinoma to characterize a new subgroup of hard-to-treat patients with unmet need in the real-world setting.
Authors: Hempel Louisa , Boos Laura Amanda , Fábregas-Ibáñez Luis , Gut Gabriele , Nowak Marta , Zoche Martin , Wicki Andreas 
Published: June 2024

8641 Background: Recent research suggests that loss of heterozygosity (LOH) in KEAP1/STK11 mutated lung adenocarcinoma (LUAD) may present a new immunological and biological aggressive subtype unresponsive to current standard of care treatment options. Currently, there is limited data on the clinical impact of LOH in KEAP1/STK11 co-alterations in real-world settings. Methods: From November 1st, 2021, to October 1st, 2023, patients with LUAD and mutations detected by FoundationOne CDx in any of the genes KEAP1, STK11, KRAS were enrolled in the study. Clinical data, including overall survival (OS), duration of response to different treatment lines (DOR), and real-world progression-free survival (rwPFS) according to the treatment lines, were retrospectively assessed in patients who had given informed general consent. Multivariate Cox regression models included patient characteristics, selected two-way interactions, OS, LOH, PD-L1 status and rwPFS for patients with STK11, KEAP1, KRAS mutations. Results: A total of 104 patients were included, 63 (60.6%) males with a median age of 64.4 years; [range: 38-90]). 23 (22.1%) patients with STK11/KEAP1/KRASmutations, 15 (14.4%) patients with KEAP1/LOH mutations, 10 (10.4%) patients with STK11/KRAS mutations and six (5.8%) patients with STK11/KEAP1. In the KEAP1/LOH mutated subgroup, median OS (mOS) was 14 months (ms), whereas in the subgroup with KEAP1/KRASmutations mOS was 13 ms. Across all groups mOS was 14 ms. Compared to Keynote 189 with a PFS of 8.8 ms, rwPFS for the first treatment line (rwPFS1) was shorter in patients with KEAP1/LOH status and KRAS/STK11 mutations at 3.5 ms and 3 ms respectively. Additionally, DOR and rwPFS for further treatment lines were analyzed according to PD-L1 and TMB status, as well as the treatment lines patients received. Conclusions: Patients with mutations on STK11/KEAP1/KRAS or with LOH presented an mOS inferior to what is currently expected from historic data for metastatic LUAD, with a worse prognosis and shorter rwPFS1 for the subgroup of K EAP1/LOH, KEAP1/KRAS and KRAS/STK11. Surprisingly, the percentage of patients carrying concurrent mutations of interest was much higher in the analyzed population than previously described, emphasizing the importance of broad NGS panel testing, including STK11 and KEAP1 mutations. Our findings based on real-world data indicate that in addition to the already known STK11/KEAP1/KRASconcomitant mutations, KEAP1/LOH mutations define a new subset of hard-to-treat genetic alterations. These patients represent a subgroup associated with primary therapy resistance, highlighting a new unmet need for tailored therapeutic strategies. Furthermore, our data emphasizes the benefit of upfront panel sequencing, including STK11/KEAP1 mutations and LOH, to identify at-need patients.
Two years of teaching close to home: Lessons learned from a near-peer model for an introductory lecture series for hematology-oncology fellows.
Authors: Iacoviello Anthony , Lam Barbara , Patell Rushad , Berry Jonathan L , Rangachari Deepa 
Published: June 2024

9027 Background: First-year hematology-oncology fellows face a large initial knowledge gap due to limited disease-specific content exposure during residency training. To facilitate their transition, we introduced a near-peer lecture series during academic year (AY) 2021-22, featuring near-peers (2nd and 3rd year [“senior”] fellows) as the primary instructors guided by content experts (disease specific faculty) [Berry, et al. JCO OP 2023]. This follow-up study’s primary aim was to assess the lectures’ continued impact on learning for 1st year fellows, as well as the impact on the educational skills of senior fellows. We also sought to assess the continued support of this format by faculty. Methods: For AY 2023-24, each rising senior fellow attended a one-hour preparatory workshop on active learning techniques in Spring 2023. They were then assigned 2-3 topics to teach and paired with ≥1 expert faculty. Lectures were conducted from July to September 2023. We administered anonymous surveys immediately post-lecture to attendees and at end-of-series to senior fellows and faculty. Results are summarized as proportions with binomial 95% confidence intervals (CI). Results: We received 109 immediate post-lecture responses for 26 lectures (66% of total lectures). Of 1st year fellow respondents (82.5% of all responses), 80% (95% CI [72-88%]) found the lectures very engaging, 82% (95% CI [76-90%]) found them relevant, 54% (95% [CI 46-62%]) felt very confident in disease diagnosis and staging, and 43% (95% CI [37-49%]) felt very confident in disease treatment following the lectures. All responding senior fellows (N=7) endorsed the lecture format. The majority of senior fellows (67%, 95% CI [50-84%]) found the one-hour workshop only somewhat helpful, and 71% (95% CI [50-92%]) felt only somewhat well equipped to give their lecture. Over half (57%, 95% CI [41-73%]) of senior fellows reused previous slide decks and did not meet with faculty in person to prepare for their sessions. On qualitative review of senior fellow feedback, common themes included time constraints and lack of structured format during the preparation phase. Of faculty respondents (N=9), 78% (95% CI [50-99%]) supported continuation of the format, but only 44% (95% CI [38-50%]) met in-person with their assigned senior fellow in advance of the teaching session. Conclusions: Our near-peer lecture series has broad support for its continuation and is meeting the needs of 1st year fellows. To better help senior fellows improve their education skills, future iterations will focus on optimizing the pre-session coaching and preparatory phase. This will include structured coaching with an expert educator for content planning and development, an augmented process for pre-session meetings between senior fellows and faculty, and greater focus on defining the optimal timeline for session preparation.
Development of a professional oncology navigation training and credentialing program: ACS Leadership in Oncology Navigation (ACS LION).
Authors: Morris Bonny , Kamal Arif , Franklin Elizabeth , Calhoun Elizabeth , Balistreri Jennifer , Sivendran Shanthi 
Published: June 2024

9045 Background: Navigation by trained professionals is a key component to improving cancer outcomes in the US, helping to ensure every cancer patient has access to timely, quality, and culturally competent care. Due to limited standardized training and lack of sustainable funding for navigation, patients are not receiving the comprehensive care they deserve. The new Center for Medicare (CMS) 2024 physician fee schedule pathway for reimbursement of non-clinical patient navigation (PN) offers a pathway to create sustainable oncology navigation. Methods: The American Cancer Society developed the Leadership in Oncology Navigation (ACS LION) training and credentialing program with the goal of increasing access to high quality, standardized navigation training in compliance with Medicare requirements and in alignment with the Oncology Navigation Standards of Professional Practice. The program includes 10 learning modules and associated quizzes and a final summative assessment that is remotely live-proctored to demonstrate learning comprehension. This mixed methods analysis includes program descriptive data and paired t-tests of pre- and post-course comprehension and qualitative thematic analysis of open-ended survey responses. Results: The ACS LION program was piloted among 11 organizations nationally, including both academic health systems and community-based organizations. Of the 79 participants, 23% were Black and 14% were Hispanic. 18% of participants had less than one year of experience and 29% had more than 5 years of experience in navigation. 28% held clinical job titles. 51% had organization-specific in-service training and only 11% had taken an external standardized training program. Compared with pre-course scores, the program was significantly associated with higher post-course self-reported comprehension of 9 CMS required PN competencies (p<0.001; p=0.08 for professionalism and ethical conduct). Qualitative analysis revealed 4 themes: learner experience, practicality, comprehensiveness, and role delineation. Post-program ratings averaged 4.5 out of 5.0, including overall learning experience, meeting a need, would recommend to others, and enhanced their professional experience. Conclusions: Pilot participants from diverse racial, ethnic, and work experience backgrounds found ACS LION to be comprehensive, engaging, and provided either critical foundational knowledge for less experienced navigators or enhanced their existing knowledge for experienced navigators, providing practical tools and resources. Pilot results informed the course that was launched nationally on Jan 1, 2024. Webinars, learning collaboratives, refresher courses, and re-credentialing will continue to be developed and offered as part of ACS LION and ACS commitment to advancing high quality professional navigation.
Exploring the digital footprint: Social media use among hematology oncology fellowship programs in the U.S.
Authors: Vegivinti Charan Thej Reddy , Thakur Rahul Kumar , Shikhrakar Shreeja , Hammami M Bakri , Ray Barun , Kakumani Kiranmayi , Kumar Abhishek 
Published: June 2024

9048 Background: Social media platforms have emerged as pivotal tools for communication, outreach, and engagement. This study aims to assess the adoption and utilization of social media among Accreditation Council for Graduate Medical Education (ACGME) accredited Hematology Oncology (HO) fellowship programs, examining the correlation between program characteristics and social media presence. Methods: A comprehensive review was conducted of all ACGME-accredited HO fellowship programs to identify their presence on popular social media platforms, Twitter/X and Instagram. Collected metrics included the presence of official accounts, the date of creation, and follower counts as of February 2023. Additional details such as university affiliation, program size, and geographic location were also gathered to understand their influence on social media usage. Results: Out of 183 programs, 54 programs (29.5%) were found to be using Twitter, while 21 programs (11.5%) had an Instagram presence. Of these, 9 programs (4.9%) had a dual presence. Regional analysis revealed that the East North Central region had the highest Twitter/X presence, with 14 programs (25.9%), while on Instagram, the Pacific region led with 5 programs (23.8%). A significant association was observed between program type (university vs. community) and Twitter/X use. Programs with a higher number of fellowship positions (four or more) were more likely to use social media. In the period post-2021, approximately 20 programs adopted Twitter, and 15 began using Instagram. Descriptive statistics, including median values and interquartile ranges for posts, followers, and accounts followed, along with verification percentages, are detailed in the accompanying table. Conclusions: The use of social media within HO fellowship programs is a strategic tool for increasing program visibility and engaging with the next generation of medical professionals. The findings highlight a predominant use of social media in larger, possibly more resource-endowed programs, and suggest that these platforms may be an effective medium for recruitment in a digital age. This study emphasizes the significance of social media in the contemporary recruitment landscape and lays the groundwork for future research on its impact on program attractiveness and applicant selection processes in the medical field. [Table: see text]
Mucoadhesive Chitosan Composite Sponge as a Carrier for β-Sitosterol Cubosomes for Thermal Burn Treatment
Authors: Khattab Abeer , Ismail Soha , Abd-Elrazek Areeg M. 
Published: June 2024

AbstractOur study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly soluble in water. Here, we have taken advantage of the unique characteristics that cubosomes have to provide as a drug delivery system. These characteristics include a large surface area, thermal stability, and the capacity to encapsulate molecules that are hydrophobic, amphiphilic, and hydrophilic. The cubosomal formulation was optimized by building a central composite design. The optimum dispersion exhibited a particle size of 88.3 nm, a zeta potential of -43, a polydispersity index of 0.358, and drug entrapment of 95.6%. It was composed of 15% w/w oleic acid and 5% w/w pluronic F127. The optimized cubosome dispersion was incorporated into a sponge formulation. The optimized cubosome sponge achieved a higher drug release compared with the cubosome dispersion. The SEM micrograph of the selected sponge showed that it has an interwoven irregular fibrous lamellar structure with low density and high porosity. The in-vivo data revealed that topical application of the β-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the β-sitosterol product (Mebo)®.
Graphical Abstract
Diazoxide-related Hyperglycemic Hyperosmolar State in a Child With Kabuki Syndrome
Authors: Kahlon Harsh , Stanley Joshua R , Lineen Cillian , Lam Carol 
Published: June 2024

Abstract
Diazoxide is a commonly used first-line medication for the treatment of hyperinsulinism. Hyperglycemia may occur with diazoxide use. However, hyperglycemic hyperosmolar state (HHS) secondary to diazoxide is an exceedingly rare but potentially life-threatening adverse effect. We present a case of a 2-year-old with Kabuki syndrome and hyperinsulinism on diazoxide. She presented with 4 days of fever, respiratory symptoms, and lethargy. She was influenza B positive. Initial workup indicated HHS, with an elevated serum glucose (47.1 mmol/L [847.8 mg/dL]; reference range 3.9-6.0 mmol/L; 70-108 mg/dL), serum osmolality (357 mmol/kg H2O; reference 282-300 mmol/kg H2O) but absent urine ketones and no metabolic acidosis (venous pH 7.34). Her course was complicated by an acute kidney injury. Management in the hospital included discontinuation of diazoxide and intravenous fluid resuscitation, following which hyperglycemia and hyperosmolarity resolved. No insulin therapy was required. She remained normoglycemic without diazoxide for 2 weeks but subsequently required restarting of diazoxide for hypoglycemia. This case highlights the need for early recognition and prompt management of diazoxide-related HHS to reduce negative outcomes. We present the first case report of a child with Kabuki syndrome and hyperinsulinism with diazoxide-induced HHS.
The Information Isolation Trope: Isolation, Infection, and Information Silos in Early American Literature
Authors: Tillman Kacy Dowd 
Published: June 2024

Abstract
Many early American novels feature at least one character who becomes physically isolated, is restricted access to communication, becomes ill, spreads their sickness, and then either dies or becomes permanently disabled. This repeated pattern of isolation, infection, information, and death/disability underscores just how concerned early Americans were with the potentially harmful effects of information silos. The concern with information siloing, at first glance, seems anachronistic to early America. Eli Pariser popularized the concept of a “filter bubble” in 2011 when lamenting the many ways that algorithms create echo chambers and political fragmentation. While this essay concurs that content-recommendation bubbles are exacerbated by new media technologies, early American novels suggest that people have been worrying about the regulation and isolation of information since the dawn of the new republic. Early American novels—particularly those published between 1789 and 1815—are often read as seduction narratives, didactic narratives, or both; this article argues that attending to this pattern offers a new way of reading early American fiction that underscores just how concerned readers and writers were with the potentially harmful effects of information silos and the regulation of information on the body, the body politic, and public health.
Manufacturing Belief: Religion, Slavery, and Benito Cereno
Authors: Traister Bryce 
Published: June 2024

Abstract
Although not typically read as either a religious text or a narrative preoccupied with religious issues, Herman Melville’s novella of maritime slave revolution and recontainment demonstrates how antebellum Americans came to “believe” in slavery. Focusing on the narrative’s staging of religious declension within the theater of enslavement aboard the San Dominick, this essay shows how the novella positions the practice of human slavery as an object of belief and obligation, thereby rendering human slavery into a coherent feature of the national landscape.
Legacies of Protest Art in Iran
Authors: Moss Anne Eakin , Haeri Niloofar , Bajoghli Narges 
Published: June 2024

Abstract
This article examines the art practice of a group of professors and students—who later came to be known as Group 57—at the Fine Arts College of the University of Tehran during the revolutionary period of 1978 to 1980. Through interviews with artists and art historical research, the authors describe the artists’ workshop where they produced posters against the Shah, the United States, and imperialism. Their posters drew on the bold colors, clear text, symbolic imagery, and easy reproducibility of international radical poster art and the early Russian revolutionary avant-garde. The authors recover these aesthetic and intellectual connections in the academic and professional training of the artists and in the art historical context of the posters themselves, examining the posters’ recent and more distant influences, and reinscribing the artists in the history of Iranian art and international art history. The authors also point toward connections between Group 57 and protest art in Iran today.
Extermination as Protection
Authors: Blacksin Isaac 
Published: June 2024

Abstract
Drawing on ethnographic fieldwork with international war reporters, this article interrogates dominant meanings for warfare and for the civilian death that results. It takes as a case study the 2016 to 2017 battle for Mosul, Iraq. Lauded reportage from Mosul revealed official underestimates of US-caused civilian harm in anti-Islamic State operations, exemplifying journalism's ability to “speak truth to power.” Yet in questioning official death tallies, journalists failed to challenge the rationale offered for this death: an accidental exception or necessary excess to justified violence. The article demonstrates how a humanitarian turn in war reportage transforms war from the effects of policy on populations to the effects of violence on the innocent. Emphasizing the morality of militarism while mystifying its political logic, news coverage of civilian death, widely presumed to function as a critique of mass violence, serves to sanction official rationales for global war.