bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propargyl-Substituted Furazanoazepines: Synthesis, Structure, Enthalpy of Formation, Ballistic Efficiency
Authors: Lempert D. B. , Ignatieva E. L. , Stepanov A. I. , Dashko D. V. , Kazakov A. I. , Nabatova A. V. , Shilov G. V. , Lagodzinskaya G. V. , Korchagin D. V. , Aldoshin S. M. 
Published: April 2024

Abstract
7-propargyl-7H-difurazano[3,4-b:3',4'-f]furoxano[3",4"-d]azepine (Az(O)Prg) and 7-propargyl-7H-trifurazano[3,4-b:3',4'-d:3",4"-f]azepine (AzPrg) are synthesized as potential dispersants of solid fuels for gas-generator engines for the first time. Their molecular structure, enthalpies of combustion and formation are determined. The relative aircraft flight range is estimated when using Az(O)Prg and AzPrg as fuel dispersants.
Gastric emptying during and following resolution of moderate diabetic ketoacidosis in type 1 diabetes: a case series
Authors: Jalleh Ryan J , Phillips Liza , Umapathysivam Mahesh M , Jones Karen L , Marathe Chinmay S , Watson Linda E , Bound Michelle , Rayner Christopher K , Horowitz Michael 
Published: April 2024

IntroductionTo use the ‘gold standard’ technique of scintigraphy to quantify gastric emptying (GE) as soon as practicable during an admission with diabetic ketoacidosis (DKA) and following its resolution at least 7 days later.Research design and methodsFive patients with type 1 diabetes, age 29±12 years; Body Mass Index 23±3 kg/m2; hemoglobin A1c 11.3%±1.9%, were studied during an admission with DKA and following its resolution. Solid and liquid GE were measured using scintigraphy. Solid emptying was assessed via the percentage intragastric retention at 100 min and that of liquid by the 50% emptying time.ResultsThere was no difference in either solid or liquid GE at the initial study compared with the follow-up. Median (IQR) solid retention was 47±20 versus 38%±33%, respectively; p=0.31, and time to empty 50% of liquid was 37±25 min versus 35±15 min, p=0.31, at the initial and follow-up GE study, respectively.ConclusionsGE of solids and liquids is not affected by moderate DKA, inferring that earlier reintroduction of oral intake may be appropriate.
Modified sutureless and glue-free method versus conventional sutures for conjunctival autograft fixation in primary pterygium surgery: a systematic review and meta-analysis
Authors: Aljahdali Faisal , Khayyat Waleed , BinYamin Abdulelah T , Al-Qahtani Sultan A , Alghamdi Mohammed D , Alsudais Ali Saleh , Alalgum Husain A , Bin Helayel Halah , AlMutlak Mohammed 
Published: April 2024

BackgroundPterygium is a common ocular surface disorder that requires surgical intervention for treatment. Conjunctival autografts are preferred over simple excision due to lower recurrence rates. This systematic review and meta-analysis compared the modified sutureless glue-free (MSGF) method with conventional sutures (CS) for conjunctival autograft fixation in primary pterygium surgery.MethodsA comprehensive search was conducted in MEDLINE, Embase, CENTRAL, Google Scholar and ClinicalTrials.gov for randomised controlled trials (RCTs) comparing MSGF and CS conjunctival autografts. Outcome measures included operation time, recurrence and postoperative complications. Standardised mean difference (SMD) and risk ratio (RR) were used for continuous and dichotomous outcomes, respectively.Results11 RCTs involving 833 participants were included. The analysis revealed that MSGF had a significantly shorter operation time compared with CS (SMD −3.704, 95% CI −5.122 to −2.287, p<0.001). CS was associated with a higher risk of foreign body sensation (RR 0.22, 95% CI 0.06 to 0.74, p=0.01). MSGF was associated with a higher risk of graft dehiscence (RR 9.01, 95% CI 2.74 to 29.68, p=0.000) and graft retraction (RR 2.37, 95% CI 1.17 to 4.77, p=0.02). No significant differences were found in recurrence, graft haemorrhage, granuloma, Dellen and conjunctival oedema.ConclusionUsing the MSGF technique in conjunctival autograft fixation for pterygium surgery reduces operation time by relying solely on the patient’s blood for fixation. However, it increases the risk of graft dehiscence and retraction. However, CS is linked to a higher likelihood of experiencing foreign body sensations. Understanding the learning curve and surgeon familiarity with novel techniques is crucial for optimising patient care and surgical outcomes, while individualised decision-making is necessary considering the advantages and disadvantages of each approach. Further research is warranted to minimise complications and optimise surgical outcomes.
Recruitment and baseline characteristics of young adults at risk of early-onset knee osteoarthritis after ACL reconstruction in the SUPER-Knee trial
Authors: Culvenor Adam G , West Thomas J , Bruder Andrea M , Scholes Mark J , Barton Christian J , Roos Ewa M , Oei Edwin H G , McPhail Steven M , Souza Richard B , Lee Jusuk , Patterson Brooke E , Girdwood Michael A , Couch Jamon L , Crossley Kay M 
Published: April 2024

ObjectivesThe study aims to (1) report the process of recruiting young adults into a secondary knee osteoarthritis prevention randomised controlled trial (RCT) after anterior cruciate ligament reconstruction (ACLR); (2) determine the number of individuals needed to be screened to include one participant (NNS) and (3) report baseline characteristics of randomised participants.MethodsThe SUpervised exercise-therapy and Patient Education Rehabilitation (SUPER)-Knee RCT compares SUPER and minimal intervention for young adults (aged 18–40 years) with ongoing symptoms (ie, mean score of <80/100 from four Knee injury and Osteoarthritis Outcome Score subscales (KOOS4)) 9–36 months post-ACLR. The NNS was calculated as the number of prospective participants screened to enrol one person. At baseline, participants provided medical history, completed questionnaires (demographic, injury/surgery, rehabilitation characteristics) and underwent physical examination.Results1044 individuals were screened to identify 567 eligible people, from which 184 participants (63% male) enrolled. The sample of enrolled participants was multicultural (29% born outside Australia; 2% Indigenous Australians). The NNS was 5.7. For randomised participants, mean±SD age was 30±6 years. The mean body mass index was 27.3±5.2 kg/m2, with overweight (43%) and obesity (21%) common. Participants were, on average, 2.3 years post-ACLR. Over half completed <8 months of postoperative rehabilitation, with 56% having concurrent injury/surgery to meniscus and/or cartilage. The most affected KOOS (0=worst, 100=best) subscale was quality of life (mean 43.7±19.1).ConclusionYoung adults post-ACLR were willing to participate in a secondary osteoarthritis prevention trial. Sample size calculations should be multiplied by at least 5.7 to provide an estimate of the NNS. The SUPER-Knee cohort is ideally positioned to monitor and intervene in the early development and trajectory of osteoarthritis.Trial registration numberACTRN12620001164987.
The VEGF-Hypoxia Signature Is Upregulated in Basal-like Breast Tumors from Women of African Ancestry and Associated with Poor Outcomes in Breast Cancer
Authors: Han Yoo Jane , Liu Siyao , Hardeman Ashley , Rajagopal Padma Sheila , Mueller Jeffrey , Khramtsova Galina , Sanni Ayodele , Ajani Mustapha , Clayton Wendy , Hurley Ian W. , Yoshimatsu Toshio F. , Zheng Yonglan , Parker Joel , Perou Charles M. , Olopade Olufunmilayo I. 
Published: April 2024

Abstract

Purpose:
Black women experience the highest breast cancer mortality rate compared with women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry.

Experimental Design:
We developed a NanoString nCounter gene expression panel and applied it to breast tumors from Nigeria (n = 182) and the University of Chicago (Chicago, IL; n = 161). We also analyzed RNA sequencing data from Nigeria (n = 84) and The Cancer Genome Atlas (TCGA) datasets (n = 863). Patient prognosis was analyzed using multiple datasets.

Results:
The VEGF-hypoxia signature was highest in the basal-like subtype compared with other subtypes, with greater expression in Black women compared with White women. In TCGA dataset, necrotic breast tumors had higher scores for the VEGF-hypoxia signature compared with non-necrosis tumors (P &lt; 0.001), with the highest proportion in the basal-like subtype. Furthermore, necrotic breast tumors have higher scores for the proliferation signature, suggesting an interaction between the VEGF-hypoxia signature, proliferation, and necrosis. T-cell gene expression signatures also correlated with the VEGF-hypoxia signature when testing all tumors in TCGA dataset. Finally, we found a significant association of the VEGF-hypoxia profile with poor outcomes when using all patients in the METABRIC (P &lt; 0.0001) and SCAN-B datasets (P = 0.002).

Conclusions:
These data provide further evidence for breast cancer heterogeneity across diverse populations and molecular subtypes. Interventions selectively targeting VEGF-hypoxia and the immune microenvironment have the potential to improve overall survival in aggressive breast cancers that disproportionately impact Black women in the African Diaspora.
Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine
Authors: Mouillet-Richard Sophie , Cazelles Antoine , Sroussi Marine , Gallois Claire , Taieb Julien , Laurent-Puig Pierre 
Published: April 2024

Abstract
Over the past decade, our understanding of the diversity of colorectal cancer has expanded significantly, raising hopes of tailoring treatments more precisely for individual patients. A key achievement in this direction was the establishment of the consensus molecular classification, particularly identifying the challenging consensus molecular subtype (CMS) CMS4 associated with poor prognosis. Because of its aggressive nature, extensive research is dedicated to the CMS4 subgroup. Recent years have unveiled molecular and microenvironmental features at the tissue level specific to CMS4 colorectal cancer. This has paved the way for mechanistic studies and the development of preclinical models. Simultaneously, efforts have been made to easily identify patients with CMS4 colorectal cancer. Reassessing clinical trial results through the CMS classification lens has improved our understanding of the therapeutic challenges linked to this subtype. Exploration of the biology of CMS4 colorectal cancer is yielding potential biomarkers and novel treatment approaches. This overview aims to provide insights into the clinico-biological characteristics of the CMS4 subgroup, the molecular pathways driving this subtype, and available diagnostic options. We also emphasize the therapeutic challenges associated with this subtype, offering potential explanations. Finally, we summarize the current tailored treatments for CMS4 colorectal cancer emerging from fundamental and preclinical studies.
An Integrated Cancer Prevention Strategy: the Viewpoint of the Leon Berard Comprehensive Cancer Center Lyon, France
Authors: Fervers Beatrice , Pérol Olivia , Lasset Christine , Moumjid Nora , Vidican Pauline , Saintigny Pierre , Tardy Juliette , Biaudet Julien , Bonadona Valérie , Triviaux Dominique , Marijnen Philippe , Mongondry Rodolf , Cattey-Javouhey Anne , Buono Romain , Bertrand Amandine , Marec-Bérard Perrine , Rousset-Jablonski Christine , Pilleul Frank , Christophe Veronique , Girodet Magali , Praud Delphine , Solodky Marie-Laure , Crochet Hugo , Achache Abdel , Michallet Mauricette , Galvez Christelle , Miermont Anne , Sebileau Damien , Zrounba Philippe , Beaupère Sophie , Philip Thierry , Blay Jean-Yves 
Published: April 2024

Abstract
This article describes some of the key prevention services in the Leon Berard Comprehensive Cancer Center (CLB) Lyon, France, which are based on clinical prevention services, outreach activities, and collaboration with professional and territorial health communities. In addition, research is embedded at all stages of the prevention continuum, from understanding cancer causes through to the implementation of prevention interventions during and after cancer. Health promotion activities in the community and dedicated outpatient primary cancer prevention services for individuals at increased risk have been implemented. The CLB's experience illustrates how prevention can be integrated into the comprehensive mission of cancer centers, and how in turn, the cancer centers may contribute to bridging the current fragmentation between cancer care and the different components of primary, secondary, and tertiary prevention. With increasing cancer incidence, the shift toward integrated prevention-centered cancer care is not only key for improving population health, but this may also provide a response to the shortage of hospital staff and overcrowding in cancer services, as well as offer opportunities to reduce carbon emissions from cancer care.
Activating Point Mutations in the MET Kinase Domain Represent a Unique Molecular Subset of Lung Cancer and Other Malignancies Targetable with MET Inhibitors
Authors: Pecci Federica , Nakazawa Seshiru , Ricciuti Biagio , Harada Guilherme , Lee Jessica K. , Alessi Joao V. , Barrichello Adriana , Vaz Victor R. , Lamberti Giuseppe , Di Federico Alessandro , Gandhi Malini M. , Gazgalis Dimitris , Feng William W. , Jiang Jie , Baldacci Simon , Locquet Marie-Anaïs , Gottlieb Felix H. , Chen Monica F. , Lee Elinton , Haradon Danielle , Smokovich Anna , Voligny Emma , Nguyen Tom , Goel Vikas K. , Zimmerman Zachary , Atwal Sumandeep , Wang Xinan , Bahcall Magda , Heist Rebecca S. , Iqbal Sumaiya , Gandhi Nishant , Elliott Andrew , Vanderwalde Ari M. , Ma Patrick C. , Halmos Balazs , Liu Stephen V. , Che Jianwei , Schrock Alexa B. , Drilon Alexander , Jänne Pasi A. , Awad Mark M. 
Published: April 2024

Abstract
Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic in a subset of papillary renal cell carcinomas. Here, using comprehensive genomic profiling among &gt;600,000 patients, we identify activating MET TKD point mutations as putative oncogenic driver across diverse cancers, with a frequency of ∼0.5%. The most common mutations in the MET TKD defined as oncogenic or likely oncogenic according to OncoKB resulted in amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling of these alterations confirmed their oncogenic potential and also demonstrated differential patterns of sensitivity to type I and type II MET inhibitors. Two patients with metastatic lung adenocarcinoma harboring MET TKD mutations (H1094Y, F1200I) and no other known oncogenic drivers achieved confirmed partial responses to a type I MET inhibitor. Activating MET TKD mutations occur in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors.
Significance: The identification of targetable genomic subsets of cancer has revolutionized precision oncology and offers patients treatments with more selective and effective agents. Here, we demonstrate that activating, oncogenic MET tyrosine kinase domain mutations are found across a diversity of cancer types and are responsive to MET tyrosine kinase inhibitors.
CD8-Targeted IL2 Unleashes Tumor-Specific Immunity in Human Cancer Tissue by Reviving the Dysfunctional T-cell Pool
Authors: Kaptein Paulien , Slingerland Nadine , Metoikidou Christina , Prinz Felix , Brokamp Simone , Machuca-Ostos Mercedes , de Roo Guido , Schumacher Ton N.M. , Yeung Yik A. , Moynihan Kelly D. , Djuretic Ivana M. , Thommen Daniela S. 
Published: April 2024

Abstract
Tumor-specific CD8+ T cells are key effectors of antitumor immunity but are often rendered dysfunctional in the tumor microenvironment. Immune-checkpoint blockade can restore antitumor T-cell function in some patients; however, most do not respond to this therapy, often despite T-cell infiltration in their tumors. We here explored a CD8-targeted IL2 fusion molecule (CD8–IL2) to selectively reactivate intratumoral CD8+ T cells in patient-derived tumor fragments. Treatment with CD8–IL2 broadly armed intratumoral CD8+ T cells with enhanced effector capacity, thereby specifically enabling reinvigoration of the dysfunctional T-cell pool to elicit potent immune activity. Notably, the revival of dysfunctional T cells to mediate effector activity by CD8–IL2 depended on simultaneous antigen recognition and was quantitatively and qualitatively superior to that achieved by PD-1 blockade. Finally, CD8–IL2 was able to functionally reinvigorate T cells in tumors resistant to anti–PD-1, underscoring its potential as a novel treatment strategy for patients with cancer.
Significance: Reinvigorating T cells is crucial for response to checkpoint blockade therapy. However, emerging evidence suggests that the PD-1/PD-L1 axis is not the sole impediment for activating T cells within tumors. Selectively targeting cytokines toward specific T-cell subsets might overcome these barriers and stimulate T cells within resistant tumors.
See related article by Moynihan et al., p. 1206 (32).
Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non–Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors
Authors: Schoenfeld Adam J. , Lee Sylvia M. , Doger de Spéville Bernard , Gettinger Scott N. , Häfliger Simon , Sukari Ammar , Papa Sophie , Rodríguez-Moreno Juan F. , Graf Finckenstein Friedrich , Fiaz Rana , Catlett Melissa , Chen Guang , Qi Rongsu , Masteller Emma L. , Gontcharova Viktoria , He Kai 
Published: April 2024

Abstract
In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non–small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. The median number of prior systemic therapies was 2 (range, 1–6). Lifileucel was successfully manufactured using tumor tissue from different anatomic sites, predominantly lung. The objective response rate was 21.4% (6/28). Responses occurred in tumors with profiles typically resistant to immunotherapy, such as PD-L1–negative, low tumor mutational burden, and STK11 mutation. Two responses were ongoing at the time of data cutoff, including one complete metabolic response in a PD-L1−negative tumor. Adverse events were generally as expected and manageable. Two patients died of treatment-emergent adverse events: cardiac failure and multiple organ failure. Lifileucel is a potential treatment option for patients with mNSCLC refractory to prior therapy.
Significance: Autologous tumor-infiltrating lymphocyte therapy lifileucel was administered to 28 patients with heavily pretreated metastatic non–small cell lung cancer (mNSCLC). Responses were observed in patients with driver mutations, and various tumor mutational burdens and PD-L1 expression, potentially addressing an unmet medical need in patients with mNSCLC refractory to prior therapy.
See related commentary by Lotze et al., p. 1366
Phosphocreatine Promotes Epigenetic Reprogramming to Facilitate Glioblastoma Growth Through Stabilizing BRD2
Authors: Chen Lishu , Qi Qinghui , Jiang Xiaoqing , Wu Jin , Li Yuanyuan , Liu Zhaodan , Cai Yan , Ran Haowen , Zhang Songyang , Zhang Cheng , Wu Huiran , Cao Shuailiang , Mi Lanjuan , Xiao Dake , Huang Haohao , Jiang Shuai , Wu Jiaqi , Li Bohan , Xie Jiong , Qi Ji , Li Fangye , Liang Panpan , Han Qiuying , Wu Min , Zhou Wenchao , Wang Chenhui , Zhang Weina , Jiang Xin , Zhang Kun , Li Huiyan , Zhang Xuemin , Li Ailing , Zhou Tao , Man Jianghong 
Published: April 2024

Abstract
Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells reprogram the epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to the elevated transcription of brain-type creatine kinase, mediated by Zinc finger E-box binding homeobox 1. PCr inhibits the poly-ubiquitination of the chromatin regulator bromodomain containing protein 2 (BRD2) by outcompeting the E3 ubiquitin ligase SPOP for BRD2 binding. Pharmacological disruption of PCr biosynthesis by cyclocreatine (cCr) leads to BRD2 degradation and a decrease in its targets’ transcription, which inhibits chromosome segregation and cell proliferation. Notably, cyclocreatine treatment significantly impedes tumor growth and sensitizes tumors to a BRD2 inhibitor in mouse GBM models without detectable side effects. These findings highlight that high production of PCr is a druggable metabolic feature of GBM and a promising therapeutic target for GBM treatment.
Significance: Glioblastoma (GBM) exhibits an adaptable metabolism crucial for survival and therapy resistance. We demonstrate that GBM stem cells modify their epigenetics by producing phosphocreatine (PCr), which prevents bromodomain containing protein 2 (BRD2) degradation and promotes accurate chromosome segregation. Disrupting PCr biosynthesis impedes tumor growth and improves the efficacy of BRD2 inhibitors in mouse GBM models.
Nós-em-obra, em-fluxo, em-incorporação.
Authors: Dias Kenia 
Published: April 2024

O objetivo desse artigo é abordar processos de criação em artes cênicas a partir da análise de trechos do diário de montagem da peça Nós do Grupo Galpão (MG) e do diário de whatsApp da Prática Aisthesis (DF). Para tanto, proponho analisá-los e relacioná-los em uma perspectiva processual, dinâmica, móvel e que está para além do armazenamento de informações, mas inseridos na complexa relação e mobilidade entre obra e processo. A reflexão é, também, sobre a manutenção dos processos nas obras a partir da ideia de fluxos, gerúndios e corporalidades presentes nas trajetórias de criação. O diálogo teórico se fundamenta nas pesquisas de criação em rede alavancadas por Cecília Salles nas quais destaca as pluralidades de pontos de vista e o aspecto relacional nos processos de criação, assim como, nos estudos de Diana Taylor que questiona e fortalece as relações entre arquivo e repertório.