bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR05: A novel kinase inhibitor for B-catenin mutant hepatocellular carcinoma
Authors: Rialdi Alexander , Duffy Mary , Scopton Alex , Lujambio Amaia , Dar Arvin , Guccione Ernesto 
Published: September 2022

Abstract
Purpose: We recently developed a chemical strategy for the diversification and disease-specific improvement of tool and FDA-approved kinase inhibitors, and sought to use this strategy for genotype-specific drug discovery in hepatocellular carcinoma (HCC). Experimental Procedures: Primary and murine-derived HCC organoids were used for drug screening. Expansive multiomic (phosphoproteomics, RNAseq, and ChIPseq) and target engagement analyses were used in combination with in vitro rescue and in vivo efficacy experiments. Data Summary: Currently there are few personalized therapeutic approaches for advanced HCC, which is a leading cause of cancer-related deaths worldwide. b-catenin (CTNNB1)-mutated HCC represents 30% of the disease and is a subset of Wnt-driven tumors particularly unresponsive to current therapies. Using focused chemical libraries derived from clinical multi-kinase inhibitor scaffolds, we screened HCC organoids to identify a CTNNB1-mutant selective small molecule that we dub WNTinib. WNTinib retained exquisite selectivity in human and murine models expressing oncogenic b-catenin, including patient samples. Our multidisciplinary approach revealed that WNTinib inhibits KIT/MAPK signaling at multiple nodes. Moreover, we demonstrate that lack of direct engagement on BRAF and p38a/b kinases differentiates WNTinib from existing clinical kinase inhibitors, is necessary to avoid compensatory feedback signaling, and thereby provides a durable and selective transcriptional block of mutant b-catenin and Wnt targets through re-activation of cytoplasmic enhancer of zest homolog 2 (EZH2). Finally, we demonstrate that the unique mechanism of WNTinib provides superior activity compared to clinical therapies in vivo, including in drug-resistant models of mutant b-catenin HCC. Conclusion: Our studies identify a novel inhibitor of the Wnt pathway and uncover a previously unknown mechanism to harness the KIT/MAPK/EZH2 pathway to potently and selectively antagonize CTNNB1-mutant HCC with an unprecedented wide therapeutic index. Our study also provides the rationale to explore WNTinib in proof-of-concept trials with enriched CTNNB1- mutant advanced HCC patients.
Citation Format: Alexander Rialdi, Mary Duffy, Alex Scopton, Amaia Lujambio, Arvin Dar, Ernesto Guccione. A novel kinase inhibitor for B-catenin mutant hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PR05.
Sociocultural Factors, Access to Healthcare, and Lifestyle: Multifactorial Indicators in Association with Colorectal Cancer Risk
Authors: Warren Andersen Shaneda , Zheng Wei , Steinwandel Mark , Murff Harvey J. , Lipworth Loren , Blot William J. 
Published: September 2022

Abstract

Black Americans of low socioeconomic status (SES) have higher colorectal cancer incidence than other groups in the United States. However, much of the research that identifies colorectal cancer risk factors is conducted in cohorts of high SES and non-Hispanic White participants. Adult participants of the Southern Community Cohort Study (N = 75,182) were followed for a median of 12.25 years where 742 incident colorectal cancers were identified. The majority of the cohort are non-Hispanic White or Black and have low household income. Cox models were used to estimate HRs for colorectal cancer incidence associated with sociocultural factors, access to and use of healthcare, and healthy lifestyle scores to represent healthy eating, alcohol intake, smoking, and physical activity. The association between Black race and colorectal cancer was consistent and not diminished by accounting for SES, access to healthcare, or healthy lifestyle [HR = 1.34; 95% confidence interval (CI),1.10–1.63]. Colorectal cancer screening was a strong, risk reduction factor for colorectal cancer (HR = 0.65; 95% CI, 0.55–0.78), and among colorectal cancer-screened, Black race was not associated with risk. Participants with high school education were at lower colorectal cancer risk (HR = 0.81; 95% CI, 0.67–0.98). Income and neighborhood-level SES were not strongly associated with colorectal cancer risk. Whereas individual health behaviors were not associated with risk, participants that reported adhering to ≥3 health behaviors had a 19% (95% CI, 1–34) decreased colorectal cancer risk compared with participants that reported ≤1 behaviors. The association was consistent in fully-adjusted models, although HRs were no longer significant. Colorectal cancer screening, education, and a lifestyle that includes healthy behaviors lowers colorectal cancer risk. Racial disparities in colorectal cancer risk may be diminished by colorectal cancer screening.

Prevention Relevance:
Colorectal cancer risk may be reduced through screening, higher educational attainment and performing more health behaviors. Importantly, our data show that colorectal cancer screening is an important colorectal cancer prevention strategy to eliminate the racial disparity in colorectal cancer risk.
See related Spotlight, p. 561
Quantifying the Effect of Physical Activity on Endometrial Cancer Risk
Authors: Kitson Sarah J. , Aurangzeb Olivia , Parvaiz Jawaria , Lophatananon Artitaya , Muir Kenneth R. , Crosbie Emma J. 
Published: September 2022

Abstract

Endometrial cancer incidence is rising, with 435,000 global cases in 2019. An effective, low-cost primary prevention strategy is required to reduce disease burden. Obesity, insulin resistance, and inflammation contribute to endometrial carcinogenesis and physical activity targets these pathways. This study sought to quantify the amount of physical activity required to impact upon endometrial cancer risk. Physical activity data from 222,031 female participants with an intact uterus in the UK Biobank study were analyzed using a multivariable Cox proportional hazards model. A systematic review of the literature was performed, searching CENTRAL, Embase, and MEDLINE databases up to April 19, 2021. Studies including participants with and without endometrial cancer investigating the effect of physical activity measured in MET-hours/week (MET-h/week) on disease risk were included. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias. Within the UK Biobank, each 1 MET-h/week increase in total physical activity was associated with a 0.2% [95% confidence interval (CI), 0.1–0.4; P = 0.020] reduction in endometrial cancer risk, equating to a 10.4% reduction if performing 50 MET-h/week or 7 hours of jogging per week. Eleven cohort and 12 case–control studies were identified in the systematic review, including 821,599 participants. One study reported a nonsignificant effect of 1 MET-h/week increases in physical activity on endometrial cancer risk (OR, 1.00; 95% CI, 0.99–1.00). Eight studies found significant reductions in disease risk of 15%–53%, but only in the most physically active individuals. Physical activity reduces endometrial cancer risk, but the effect size appears small. Regular vigorous activity should be encouraged to maximize the health benefit observed.

Prevention Relevance:
Effective, low-cost primary prevention strategies are urgently needed to tackle the rapid global increase in endometrial cancer. We sought to quantify the effect of physical activity on endometrial cancer risk, noting a linear inverse relationship influenced by body mass index. The most beneficial type and amount of activity remain unclear.
What Are the Factors Underlying Colorectal Cancer Health Disparities?
Authors: Petrick Jessica L. , Barber Lauren E. , Rosenberg Lynn 
Published: September 2022

Abstract
Black Americans have the highest colorectal cancer incidence and mortality rates of any U.S. racial/ethnic group. Warren Andersen and colleagues report that sociocultural, lifestyle, and healthcare factors did not explain the racial disparity in colorectal cancer incidence, but colorectal cancer screening lessened the disparity. While screening is a cornerstone of colorectal cancer prevention, an improved understanding of etiologic factors may inform additional strategies for primary prevention or risk stratification. As important “established” colorectal cancer risk factors have not been corroborated for Black Americans, this begs the question of what other etiologic factors are important for colorectal cancer development in Black American populations.
See related article, p. 595
Violencia simbólica en relaciones de pareja desde la marginalidad en mujeres jóvenes
Authors: Cadavid-Marín Angela María , Marínez-Garcés Janier Deyanira 
Published: September 2022

(analítico)El método biográfico narrativo permitió escuchar a seis mujeres jóvenes que habitan contextos marginales. A partir de un diseño narrativo, se concretaron narrativas biográficas; en ellas expusieron los modos como han configurado sus relaciones de pareja en torno a las prácticas y discursos de la violencia simbólica, dejando al descubierto una realidad atravesada por la violencia de un sector enclavado en el olvido institucional y el señalamiento colectivo. El análisis de la información se realizó mediante un Biograma, el cual permitió encontrar que la despolitización y la idealización son los modos como han construido sus relaciones. La relevancia de este estudio se centra en dar a conocer la resistencia a los mecanismos de poder como posibilidad de transformar la construcción de amor que habitualmente se ha promovido en otras mujeres..
Palabras clave: Jóvenes; marginalidad; relaciones (de pareja); violencia (simbólica); despolitización; idealización.
A new species and record of Biancolina Della Valle, 1893 (Amphipoda, Senticaudata, Ampithoidae) from the Southwestern Atlantic
Authors: Andrade Renan de Melo , Souza-Filho Jesser Fidelis 
Published: September 2022

Here we describe a new species of Biancolina from Pernambuco, Brazil, found in association with the brown algae Sargassum spp., between 0.5 and 1.0 m depth. The new species differs from its congeners mainly by the following combination of characters: antenna 1 twice the length of antenna 2, lacinia mobilis present in both mandibles, article 4 of the maxilliped bulbose; coxa 6 with anteroventral lobe well developed as in posteroventral lobe, peduncle of uropod 1 weakly setose, palm of pereopods 5-7 lacking robust seta. This is the first record of Biancolina from the southwestern Atlantic.
Recensional Traces in Codex Vaticanus in the Light of Papyrus 967
Authors: Candido Dionisio 
Published: September 2022

Abstract
This article focuses on some readings of the book of Esther in Codex Vaticanus (4th century CE), unanimously regarded as the best witness of the Old Greek text. A first comparison is made with the text of 𝔓 967 (3rd century CE), a special papyrus within the Greek textual tradition. All the relevant differences between the two are considered. Once scribal error is excluded, attention is directed to possible parallel readings with the Masoretic Text in order to ascertain whether these readings show traces of a revision of the text of Codex Vaticanus (B) towards MT.
Observations Concerning the Origins and the Relation of Codex Vaticanus to Codex Sinaiticus
Authors: Kreuzer Siegfried 
Published: September 2022

Abstract
This paper analyzes the origin of Codex Vaticanus and its relation to Codex Sinaiticus. It presents observations that point towards an origin in Caesarea/Palaestina. Although most authors who have written about the relation and origin of Codex Vaticanus and Codex Sinaiticus seem to be convinced about their view, it is, as even some quite determined authors admit, a matter of interpretation of some details. In this situation, additional observations may be welcome.
Financial Leverage, Innovation and Cournot Output: Limited Liability Effect Under Demand Uncertainty
Authors: Saxena Mohina , Bhattacharyya Surajit 
Published: September 2022

We address the strategic interdependence among capital structure, firm-level (process) innovation, and subsequent output decisions. In the backdrop of the limited liability effect, the interlinkage among financial and real variables is established through a three-stage game. The levered duopolist produces higher output and earns a larger profit than its unlevered counterpart. Even the industry output is higher when one of the duopolists is levered. However, if the levered duopolist undertakes investment in (process) innovation, then the debt-financed innovation induced output is larger than the innovation-led output of a completely equity financed firm. The levered innovative firm eventually becomes a monopolist by driving out the unlevered innovative duopolist. JEL Codes: D21, G32, L13, O31
Burnout prevalence and degree among undergraduate medical students in Indonesia during 1 month of the COVID-19 pandemic: A cross-sectional descriptive survey
Authors: Cipta Darien Alfa , Wijovi Felix , Melisa Leslie , Lili Rossalina , Marcella Elizabeth , Tancherla Angeline , Siswanto Febby Gunawan , Adiya Dewa Ayu Kalista Liani , Chen Sharon , Dermawan Gabriel Julio Caesar Ika , Louis Mellybeth Indriani , Citraningtyas Theresia , Molodynski Andrew 
Published: September 2022

Background: Medical students are under high pressure to perform academically and also face the impact of the COVID-19 pandemic, putting them at risk of developing burnout. Aims: This study aims to evaluate the prevalence and degree of burnout among medical students in Indonesia during 1 month of the COVID-19 pandemic. Methods: From April to May 2021, we conducted an online survey of Indonesian medical students to assess burnout (using Maslach Burnout Inventory-Student Survey, MBI-SS). Results: A total of 1,947 students from 27 universities participated in the study. About 35.5% had burnout, 41.7% with a moderate to high level of emotional exhaustion, 45% had moderate to high level of depersonalization and 66.7% had a low level of personal accomplishment. Conclusion: A total of 35.5% of medical students in our sample experienced burnout. We suggest further research to explore and identify factors related to these findings and the need for potential interventions at global and national level to enhance the well-being of medical students.
Valtrate antagonizes malignant phenotypes of lung cancer cells by reducing SLC7A11
Authors: Xu Wei , Yu Huan 
Published: September 2022

Objectives This research explored the efficacy of valtrate (Val) in lung cancer (LC). Methods A549 and H1299 cells were dealt with Val. SLC7A11 was overexpressed by cell transfection. Xenograft model was established in nude mice. Cell viability, proliferation and apoptosis were measured by CCK-8, EdU and Annexin-V and propidium iodide staining, respectively. Ferroptosis was assessed by iron assay kit. reactive oxygen species level was tested by ROS assay kit. Histopathological changes in tumor tissues were analyzed by HE staining. Protein expression was analyzed employing Immunohistochemical staining and western blot. Results A549 and H1299 cell viability were notably lowered by Val in a concentration-dependent way. Cell proliferation was markedly repressed by 10 and 20 μM of Val, while apoptosis and ROS generation were markedly augmented. SLC7A11 and GPX4 expression was both distinctly lowered, while Fe2+ level was remarkably improved by 10 and 20 μM of Val. However, 20 μM of Val-triggered effects were distinctly counteracted by SLC7A11 overexpression. In vivo assay revealed that both tumor volume and weight were distinctly declined by 10 mg/mL Val. The variations of proliferation, apoptosis and ferroptosis-related proteins were in line with the results in vitro assay. Conclusion Val might antagonize malignant phenotypes of LC cells by reducing SLC7A11.
Effects of acupuncture on microglial polarization and the TLR4/TRIF/MyD88 pathway in a rat model of traumatic brain injury
Authors: Cao Lu-Xi , Lin Shu-Jun , Zhao Si-Si , Wang Shi-Qi , Zeng Hai , Chen Wen-An , Lin Zhuo-Wen , Chen Jia-Xu , Zhu Ming-Min , Zhang Yi-Min 
Published: September 2022

Objective: Neuroinflammation caused by traumatic brain injury (TBI) can lead to neurological deficits. Acupuncture can inhibit neuroinflammation and promote nerve repair; however, the specific mechanism is still unclear. The purpose of this study was to explore whether acupuncture could modulate the M1 and M2 phenotypic polarization of microglia in a rat model of TBI via the toll-like receptor 4 (TLR4)/intracellular toll-interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-β (TRIF)/myeloid differentiation factor 88 (MyD88) pathway. Methods: A total of 90 adult male Sprague-Dawley (SD) rats, SPF grade, were randomly divided into a normal group, model group and acupuncture group. Each group was further divided into three subgroups (first, third, and fifth day groups) according to the treatment time ( n = 10 rats/subgroup). We used the modified neurological severity score (mNSS) method to quantify neurological deficits before and after modeling. We used Nissl staining to observe the pathological changes in brain tissue, flow cytometry to detect the proportion of M1 and M2 polarized microglia in the injured area on the first, third and fifth day, and co-immunoprecipitation (Co-IP) to examine TLR4/TRIF/MyD88 expression in microglia on the first, third and fifth day, as well as expression of the amount of binding of TLR4 with TRIF and MyD88. Results: Compared to the model group, mNSS in the acupuncture group gradually decreased and pathological morphology improved. The proportion of CD11b/CD86 positive cells was decreased, while that of CD11b/CD206 was increased in the acupuncture group. Expression of IP TLR4, IP TRIF and IP MyD88 also decreased in the acupuncture group. Conclusion: The results of this study demonstrate that one of the mechanisms through which acupuncture mitigates neuroinflammation and promotes nerve repair in TBI rats may be inhibition of M1 phenotypic polarization and promotion of M2 phenotypic polarization through inhibition of the TLR4/TRIF/MyD88 signaling pathway.
Stability of coagulation factors in feline fresh frozen plasma intended for transfusion after 1 year of storage
Authors: Blasi-Brugué Carles , Ferreira Rui RF , Sanchez Ignacio M , de Matos Augusto JF , Ruiz de Gopegui Rafael 
Published: September 2022

Objectives The most common use of plasma transfusion is for haemostatic purposes, but coagulation factor activities in stored feline plasma are unknown. The concentration and stability of coagulation factors I (fibrinogen), II, V, VII, VIII, IX, X, XI and XII in feline fresh frozen plasma (fFFP) stored for 1 year were studied. Methods Fifty-five units of fFFP were produced from 55 fresh whole-blood donations obtained from indoor healthy blood donor cats. Twenty-one units were stored for <2 weeks (T0) and 34 were stored for 1 year (T1). After the completion of storage, specific coagulation factor activities for factors II, V, VII, VIII, IX, X, XI and XII were tested using modified one-stage activated partial thromboplastin or prothrombin time assays. Fibrinogen was determined using the Clauss method. Results Significantly decreased activities were observed for factors II (T0: 101.94% ± 19.06%; T1: 73.23% ± 39.06% [ P = 0.001]), VII (T0: 102.78% ± 24.69%; T1: 60.08% ± 38.17% [ P <0.001]), VIII (T0: 77.52% ± 30.39%; T1: 50.32% ± 23.8% [ P = 0.001]), XI (T0: 88.76% ± 22.73%; T1: 66.28% ± 22.2% [ P = 0.001]) and XII (T0: 89.50% ± 21.85%; T1: 55.46% ± 23.18% [ P <0.001]) when comparing units at time 0 and after 1 year of storage. No significant difference was observed for factors IX (T0: 84.86% ± 29.35%; T1: 71.37% ± 22.23% [ P = 0.064]) and X (T0: 96.24% ± 25.1%; T1: 83.91% ± 49.54% [ P = 0.236]). Unexpectedly, a significant increase was observed for factor V (T0: 71.94% ± 24.14%; T1: 97.89% ± 62.33%; P = 0.046). Fibrinogen was 2.76 ± 1.09 g/l at T1. Factors VIII, XII and VII had the lowest mean activities after 1 year. Conclusions and relevance Although a decrease in most coagulation factors activities was noted with storage, 1-year-old fFFP was haemostatically active in vitro. The most suitable factors for quality control assessment of fFFP are factors VII and VIII. Approximately 13–20 ml/kg of fFFP is required to administer a minimum of 10 IU/kg coagulation factor activity.
Factory-Calibrated Continuous Glucose Monitoring System Accuracy During Exercise in Adolescents With Type 1 Diabetes Mellitus
Authors: Dyess Ryan J. , McKay Timothy , Feygin Yana , Wintergerst Kupper , Thrasher Bradly J. 
Published: September 2022

Background: Continuous glucose monitors (CGMs) are widely used for individuals with diabetes mellitus, particularly those with type 1 diabetes (T1D). Advancements in CGM technology allow for glycemic assessment without capillary glucose measurements as many come factory calibrated. However, exercise, an essential component of diabetes care, has been reported to alter accuracy of earlier generation CGM. Considering the importance of physical activity for individuals with T1D and the progression of CGM technology, we aimed to investigate the accuracy of the Dexcom G6 during physical activity. Methods: Adolescents (ages 13-20 years) exercised on a treadmill for 40 minutes, with a 10-minute break at minute 20. We obtained paired CGM and glucometer measurements before and every 10 minutes during and after exercise. Accuracy analysis was determined by mean absolute relative difference (MARD), mean absolute difference (MAD), and Clarke Error Grid Analyses. Results: Mean absolute relative difference and MAD increased during exercise (14%-33% and 24.3-34 mg/dL) but improved after exercise. We noted certain CGM locations produced greater changes in accuracy as MARD and MAD increased markedly when the CGM was on the buttocks (18%-46% and 30-41 mg/dL). We also noted decreased odds of Zone A in the Clarke error grid when the CGM was on the buttocks compared to the abdomen (odds ratio [OR]: 0.146; P = 0.0003; 95% CI = 0.052-0.415). Conclusions: This CGM system showed alterations in accuracy during exercise. Our findings additionally suggest interstitial fluid changes in muscles during exercise alter accuracy of CGM; however, additional research is required.