bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic implications of phosphoproteomics in molecular cancer diagnostics.
Authors: Schneider Annika , Woortman Julia , Jensen Cecilia Bang , Sakhteman Amirhossein , Teleanu Maria-Veronica , Horak Peter , Kreutzfeldt Simon , Hutter Barbara , Huellein Jennifer , Resch Moritz , Stange Christoph , Lee Chien-Yun , Witt Olaf , Jones David T.W. , Hübschmann Daniel , Pfister Stefan M. , Weichert Wilko , The Matthew , Froehling Stefan , Kuster Bernhard 
Published: June 2024

3068 Background: Precision oncology approaches employing genomics-guided targeted therapies for individual patients have provided significant survival benefits in several cancer types. However, varying response rates in solid malignancies, many patients without actionable genomic lesions, and increasing evidence that non-genomic mechanisms may play an important role in tumors indicate that genomics alone is often insufficient to inform and guide the clinical care of patients. Since most targeted anti-cancer drugs inhibit the activity of protein kinases, measuring the tumor phosphoproteome as a direct readout of oncogenic pathway activity is poised to enhance molecular stratification. Methods: We established a clinical (phospho)proteomic workflow for integration into the molecular tumor board (MTB) workflow of the Germany-wide INFORM (for children with relapsed cancers) and MASTER (for young adults with refractory cancers and patients with rare tumors) registry studies and profiled > 1000 tumor tissue specimen from patients enrolled in the DKFZ/NCT/DKTK MASTER study or the INFORM registry trial. To assess the aberrant activity of druggable signaling pathways, we developed a new tumor pathway activity (TUPAC) scoring methodology using expression data of > 8,000 proteins and > 20,000 phospho-sites per patient in a heterogeneous pan-cancer cohort. TUPAC scores integrate protein expression and phosphopeptide abundance data at several levels to detect aberrant signaling pathway activities of several interdependent oncogenic signaling pathways within one tumor specimen. Results: We show for the first time that comprehensive (phospho)proteome profiling is feasible and informative in a real-world prospective precision oncology setting. Discussion of (phospho)proteomic data of > 500 prospective patients in weekly MTB meetings revealed that adding a (phospho)proteomic layer can supply critical information for personalized therapies that is not discernible from genomic and transcriptomic data. In an independent value evaluation (329 target recommendations in 104 patients), the phosphoproteome layer was decisive in 22% of all recommended targets. Based on anecdotal cases with available clinical follow-up, we provide evidence that (phospho)proteome profiling carries important diagnostic value by detecting actionable tumor-driving kinase signaling in patients without actionable genomic lesions or by functionalizing genomic variants of unknown significance. Conclusions: Measuring the tumor phosphoproteome as a direct readout of oncogenic pathway activity is feasible and adds complementary, therapy-relevant information in a real-world prospective precision oncology setting.
CDK7 as a biomarker to predict response to etoposide and carboplatin treatment in limited-stage small cell lung cancer with surgical resection.
Authors: Tong Shanshi , Lin Chengbin , Shen Weiyu 
Published: June 2024

e20104 Background: The etoposide and carboplatin (EC) treatment has achieved great success in the adjuvant therapy of small cell lung cancer (SCLC), but its response rate is still low. However, there are currently no good biological indicators to suggest EC treatment sensitivity in limited-stage small cell lung cancer (LS-SCLC) patient with surgical resection. We aimed to explore reliable biomarkers for EC treatment during adjuvant therapy. Methods: We chose LS-SCLC patients undergoing adjuvant etoposide and carboplatin (4 cycles) after surgical resection in Ningbo Medical Center Lihuili Hospital from Jan, 2016 to Dec, 2023. Assessments of status including complete remission (CR), partial remission (PR), disease stable (SD) and progressive disease (PD) were according to the efficacy evaluation criteria of solid tumor (RECIST) version 1.1. We collected the clinical characteristics and overall survival (OS) of LS-SCLC patients for analysis. The formaldehyde-fixed, paraffin-embedded samples were collected to conduct immunohistochemistry (IHC) of CDK7 (CST, 2916, 1:1000). The H-score was calculated by IHC Profiler. All statistical analyses were evaluated using Graphpad and Excel. P value < 0.05 were considered statistically significant. Results: Clinical characteristics were displayed in table. The CDK7 expression was significantly correlated with the responsivity. Patients with higher CDK7 expression levels had lower responsivity to EC therapy, while there is no correlation between other clinical indicators (age, gender, smoke, SCLC type and ki-67 index) and EC therapy responsivity. Moreover, the expression of CDK7 and OS displayed significantly negative correlation (P < 0.05). Patients were divided into two groups depends on CDK7 expression. The Kaplan-Meier curves shows that OS was significantly different (P<0.01). Conclusions: Our study indicated that CDK7 acted as a promising biomarker for both EC treatment sensitivity and clinic outcome prediction in LS-SCLC patients with surgery. [Table: see text]
Effect of CDC7 inhibition and MYC degradation on neuroendocrine transformation in the lung and prostate cancer.
Authors: Quintanal-Villalonga Alvaro , Kawasaki Kenta , Redin Esther , Rakhade Swanand , Durani Vidushi , Sabet Amin , Karthaus Wouter , Zaidi Samir , Zhan Yingqian A. , Manoj Parvathy , Sridhar Harsha , Zhong Hong , Mello Barbara , Ciampricotti Metamia , Bhanot Umesh , Haffner Michael C. , Socci Nicholas D. , Yu Helena Alexandra , Chan Joseph Minhow , Rudin Charles M. 
Published: June 2024

e20105 Background: Neuroendocrine (NE) transformation occurs as a mechanism of resistance to targeted therapy in up to 14% and 30% of EGFR-mutant lung and AR-dependent prostate adenocarcinomas, respectively, leading to poor prognosis. Even if we know the tumor population at high risk of transformation ( TP53/RB1-mutated), no therapies to prevent NE relapse are currently available. Methods: To identify therapeutic vulnerabilities for tumors undergoing NE transformation, we performed an in vitro CRISPR screen in a NE-transformed lung tumor model, followed by functional validation in in vivo prostate and lung models of NE transformation, including pharmacologic as well as genetic (isogenic cell line with overexpression or knock of CDC7) validation. Results: Our screen identified CDC7, involved in DNA replication and DNA damage response, as a potential therapeutic target in this setting. Proteogenomic analyses revealed CDC7 upregulation in lung and prostate clinical samples undergoing NE transformation, detected already in pre-transformation adenocarcinomas. Importantly, TP53/RB1-inactivation induced sensitivity to the CDC7 inhibitor simurosertib, unraveling a therapeutic vulnerability in tumors at high risk of NE transformation. Thus, we tested the combination of simurosertib with targeted therapy in vivo in different lung and prostate patient-derived models of NE transformation. In these, simurosertib was able to suppress NE transformation and dramatically delay tumor relapse. Trajectory analysis on single-cell transcriptomic data for such models revealed a NE transformation transcriptional program occurring already in the untreated tumors before transformation. CDC7 inhibition led to increased proteasomal activity and degradation of MYC, a stemness transcription factor involved in NE transformation. Ectopic overexpression of MYCT58A, a proteasome degradation-resistant MYC isoform, rescued the NE phenotype in these transformation models, suggesting that CDC7 inhibition-induced MYC degradation is the mechanism by which NE transformation is prevented. Conclusions: In sum, CDC7 inhibition may suppress, or at least dramatically delay NE transformation in patients with lung and prostate adenocarcinomas at high risk of transformation, by inducing MYC proteasomal degradation. The clinical availability of CDC7 inhibitors, currently in phase II clinical trials after demonstrating tolerability and preliminary efficacy, will allow rapid translation of these results into the clinics.
Real world outcomes in extensive stage small cell lung cancer (ES-SCLC) treated with consolidative thoracic radiation (cTRT) and chemoimmunotherapy (CIT): A population level study.
Authors: Gibson Amanda Williams , Dean Michelle Liane , Kerba Marc , Navani Vishal 
Published: June 2024

e20111 Background: Despite recent survival improvements from the combination of immune checkpoint inhibitors (ICI) with chemotherapy for patients with ES-SCLC, outcomes remain limited for the majority of patients. Addition of cTRT may elicit a synergistic response and contribute to improved disease control and survival, but there is limited data supporting routine use from either the trial or real world contexts. This study aims to investigate the safety and time-to-event outcomes of patients treated with CIT and cTRT. Methods: Demographic, clinical, treatment and outcome details were extracted from the Glans-Look Lung Cancer Research Database, a province-wide real-world outcomes registry of patients treated in routine practice. A population-level cohort of ES-SCLC patients receiving CIT and cTRT between 2019 and 2023 were identified. Results: 30 patients were identified. Median age was 68y. At CIT initiation; 63% had ECOG performance status ≤ 1, 17% had brain metastases; 20% received prophylactic cranial irradiation. CIT was comprised of platinum-etoposide and ICI: durvalumab (67%) or atezolizumab (33%), followed by maintenance ICI (median 5.8 months). cTRT was administered a median 4.8 months after CIT initiation; n=13 (43%) received 30Gy/10, n=2 (7%) received dose escalation to 40-45Gy in 14-20 fractions, and n= 15 (50%) received 20Gy-25Gy over 5-10 fractions. Reasons for discontinuation of CIT were primarily to progressive disease (n=18, 75%); with n=16 patients receiving second line systemic treatment (94% chemotherapy, 6% durvalumab rechallenge), and n=1 receiving additional thoracic stereotactic ablative body radiation. Post-cTRT pneumonitis was recorded in n=3 (10%) of patients, ranging from (CTCAE v5.0 Grade 1-3 severity), requiring hospitalization + treatment break (n=1), ICI termination (n=1), or resolving without intervention (n=1). Time-to-event outcomes are presented in the table. Receiving durvalumab as opposed to atezolizumab did not impact either mPFS (10 vs. 12 months, log rank=0.4; HR: 1.3 [95% CI: 0.8 - 5.9], p=0.12) or OS (17 vs. 13.2 months, log rank p=0.87; HR: 2.2 [95% CI: 0.4 – 4.4], p=0.67). Conclusions: ES-SCLC treatment comprised of both CIT and cTRT appears feasible and effective in among real-world patients. Pneumonitis, a potential complication of combined ICI and thoracic radiation, was infrequently observed in this cohort. Use of cTRT in addition to CIT appears to numerically surpass the ~13-month mOS observed within clinical trials which used first-line CIT without additional cTRT for ES-SCLC. [Table: see text]
Prospective Associations of Maternal Cardiometabolic Health With Children Cardiometabolic Health at Ages 3 to 6 Years
Authors: Jing Guangzhuang , Ye Peiqi , Wei Qian , Zou Jiaojiao , Zhang Yunhui , Shi Huijing 
Published: June 2024

Abstract

Objective
Maternal cardiometabolic health (MCMH) may have critical effects on offspring lifetime cardiometabolic health (CMH), whereas evidence on the relationship between MCMH during pregnancy and children CMH (CCMH) at ages 3∼6 years remains unknown.

Method
The study included 1478 mother-child dyads from the Shanghai Maternal-Child Pairs Cohort study. MCMH was examined at a mean of 27.8 (24-36) weeks’ gestation based on 8 metrics of the “Life Essential 8” framework involving prepregnancy body mass index, total cholesterol, glucose level, blood pressure, physical activity, sleep, diet quality, and nicotine exposure. CCMH was examined at the age of 3 to 6 based on 5 metrics including body mass index, physical activity, sleep health, diet quality, and nicotine exposure. To validate the robustness of the main analysis, 499 children were selected to reevaluate CCMH by 6 metrics (adding blood pressure) for sensitivity analysis.

Results
Among 1478 mother-child dyads, the mean (SD) MCMH during pregnancy and CCMH scores were 67.07 (SD 8.82) and 73.80 (SD 10.75), respectively. After adjusting important confounders, each 10-point increase in (more favorable) MCMH score was significantly associated with a higher CCMH score [β: .85; 95% confidence interval (CI): .22, 1.47]. Subgroup analysis showed similar results in girls but not in boys. For cardiometabolic risk factors in children, the risk of overweight/obesity and hypertension in children decreased with increased MCMH score [overweight/obesity, relative risks (RRs): .98, 95% CI: .96, .99; hypertension, RRs: .66, 95% CI: .47, .92]. Sensitivity analysis showed similar results.

Conclusion
Better MCMH in pregnancy was associated with better CCMH at ages 3∼6 years.
Foraging task specialization in honey bees (Apis mellifera): the contribution of floral rewards to the learning performance of pollen and nectar foragers
Authors: Moreno Emilia , Arenas Andrés 
Published: June 2024

ABSTRACT
Social insects live in communities where cooperative actions heavily rely on the individual cognitive abilities of their members. In the honey bee (Apis mellifera), the specialization in nectar or pollen collection is associated with variations in gustatory sensitivity, affecting both associative and non-associative learning. Gustatory sensitivity fluctuates as a function of changes in motivation for the specific floral resource throughout the foraging cycle, yet differences in learning between nectar and pollen foragers at the onset of food collection remain unexplored. Here, we examined nectar and pollen foragers captured upon arrival at food sources. We subjected them to an olfactory proboscis extension reflex (PER) conditioning using a 10% sucrose solution paired (S10%+P) or unpaired (S10%) with pollen as a co-reinforcement. For non-associative learning, we habituated foragers with S10%+P or S10%, followed by dishabituation tests with either a 50% sucrose solution paired (S50%+P) or unpaired (S50%) with pollen. Our results indicate that pollen foragers show lower performance than nectar foragers when conditioned with S10%. Interestingly, performance improves to levels similar to those of nectar foragers when pollen is included as a rewarding stimulus (S10%+P). In non-associative learning, pollen foragers tested with S10%+P displayed a lower degree of habituation than nectar foragers and a higher degree of dishabituation when pollen was used as the dishabituating stimulus (S10%+P). Altogether, our results support the idea that pollen and nectar honey bee foragers differ in their responsiveness to rewards, leading to inter-individual differences in learning that contribute to foraging specialization.
Relative importance of intensity and spectrum of artificial light at night in disrupting behavior of a nocturnal rodent
Authors: Longcore Travis , Villanueva Sophia Anne Marie B. , Nguyen-Ngo Kyle , Ghiani Cristina A. , Harrison Benjamin , Colwell Christopher S. 
Published: June 2024

ABSTRACT
The influence of light spectral properties on circadian rhythms is of substantial interest to laboratory-based investigation of the circadian system and to field-based understanding of the effects of artificial light at night. The trade-offs between intensity and spectrum regarding masking behaviors are largely unknown, even for well-studied organisms. We used a custom LED illumination system to document the response of wild-type house mice (Mus musculus) to 1-h nocturnal exposure of all combinations of four intensity levels (0.01, 0.5, 5 and 50 lx) and three correlated color temperatures (CCT; 1750, 1950 and 3000 K). Higher intensities of light (50 lx) suppressed cage activity substantially, and consistently more for the higher CCT light (91% for 3000 K, 53% for 1750 K). At the lowest intensity (0.01 lx), mean activity was increased, with the greatest increases for the lowest CCT (12.3% increase at 1750 K, 3% increase at 3000 K). Multiple linear regression confirmed the influence of both CCT and intensity on changes in activity, with the scaled effect size of intensity 3.6 times greater than that of CCT. Activity suppression was significantly lower for male than for female mice. Assessment of light-evoked cFos expression in the suprachiasmatic nucleus at 50 lx showed no significant difference between high and low CCT exposure. The significant differences by spectral composition illustrate a need to account for light spectrum in circadian studies of behavior, and confirm that spectral controls can mitigate some, but certainly not all, of the effects of light pollution on species in the wild.
PRP DIVA PORTELA: EXPERIÊNCIAS FORMATIVAS
Authors: Moraes Queiroz de Melo Tatiana , Damasceno de Jesus Débora , Leite Rodrigues Tainara , De Jesus Bacelar Joice Ellen , Sampaio Santos Joicy Elen , Regis Souza Ana Carolina , Pereira de Azevedo Freitas Denize 
Published: June 2024

O presente relato de experiência tem por finalidade apresentar as experiências pedagógicas que foram vivenciadas por meio do Programa de Residência Pedagógica (PRP). Este programa intenciona o aperfeiçoamento da formação docente, promovendo a imersão dos graduandos de licenciaturas na educação básica. Especificamente, neste estudo, o trabalho foi desenvolvido com os Residentes do Curso de Licenciatura em
Educação Física da Universidade Estadual de Feira de Santana (UEFS). A escola campo das intervenções foi o Colégio da Polícia Militar Diva Portela, localizado no município de Feira de Santana. As observações e intervenções foram desenvolvidas com turmas dos Anos Finais do Ensino Fundamental e as do Ensino Médio. Concluímos que os conteúdos da Educação Física são de suma importância no ambiente escolar contribuindo significativamente para a formação humana do estudante ao tematizar fatores sociais, ambientais, motores e históricos. Ainda destacamos que a imersão das Residentes no ambiente escolar possibilitou que as experiências pedagógicas, desde o planejamento ao desenvolvimento das aulas até a constatação dos desafios pedagógicos, potencializaram a construção de uma visão crítica e reflexiva, materializando-se como uma experiência enriquecedora para a formação docente de cada um dos envolvidos.
Acceptance and commitment therapy for patients with chronic pain: A systematic review and meta-analysis on psychological outcomes and quality of life
Authors: Ye Lu , Li Yunhua , Deng Qingchuan , Zhao Xin , Zhong Lili , Yang Li 
Published: June 2024

Objectives
To assess the efficacy of acceptance and commitment therapy (ACT) for patients with chronic pain.

Materials and methods
The research conducted a systematic search of the Cochrane Library, Web of Science, PubMed, EMBASE, PsycINFO, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases following the PRISMA guidelines. The retrieval time limit was from the establishment of the database to October 2023. A meta-analysis was carried out for the randomized controlled trials (RCTs) that meet the inclusion and exclusion criteria by using RevMan 5.3.

Results
Twenty-one RCTs were included. At post-treatment, a significant medium effect size (ES) was found in measuring pain interference, functional impairment, pain acceptance, psychological inflexibility, and depression; Pain intensity, anxiety, and quality of life (QOL) had a small ES. At three months post-treatment, a large ES was found in measuring functional impairment, and a medium ES was found in the other indicators.

Conclusion
The researchers provided evidence for the effectiveness of ACT as an intervention for patients with chronic pain, which can be applied by clinicians or nurses in practice. Future research should explore the applicability of ACT to different pain conditions and modalities.

Implications for nursing
Post-treatment data highlight the efficacy of ACT in moderating pain-related outcomes. Clinical nurses are encouraged to incorporate ACT into routine patient education and interventions, including promoting pain acceptance, promoting mindfulness practices, and using cognitive stress reduction techniques. Standardized follow-up after an ACT intervention for patients with chronic pain is critical, including regular assessment, feedback, and realignment of treatment strategies. Overall, ACT became an important tool for nurses to improve the lives of patients with chronic pain.
Pacific Presences: Volume 1: Oceanic Art and European Museums, Lucie Carreau, Alison Clark, Alana Jelinek, Erna Lilje and Nicholas Thomas (eds) (2018)
Authors: Mückler Hermann 
Published: June 2024

Review of: Pacific Presences: Volume 1: Oceanic Art and European Museums, Lucie Carreau, Alison Clark, Alana Jelinek, Erna Lilje and Nicholas Thomas (eds) (2018)
Leiden: Sidestone Press, 253 pp.,
ISBN 978 9 08890 589 6 (pbk), €45

Pacific Presences: Volume 2: Oceanic Art and European Museums, Lucie Carreau, Alison Clark, Alana Jelinek, Erna Lilje and Nicholas Thomas (eds) (2018)
Leiden: Sidestone Press, 511 pp.,
ISBN 978 9 08890 626 8 (pbk), €85
Understanding Intercultural Communication as a Condition for Sustainable Development
Authors: Aleksandrova Olena , Kolinko Marina , Ishchuk Alla , Kozlovets Mykola , Petryshyn Halyna , Hotsalyuk Alla , Taran Ganna 
Published: June 2024

Intercultural communication plays a significant role in promoting the principles of sustainable development by fostering global interactions, resolving conflicts, and facilitating cultural exchange. In this study, diverse aspects of intercultural communication are investigated, with the highlight of its significance in shaping fresh social dynamics across various cultural landscapes. The phenomenon of ‘communicative space’ is depicted as a vibrant arena where individuals from different cultures share their perspectives, influencing both the potential for interaction and the obstacles to cross-cultural understanding. Language, as the socio-cultural space of speech activity, plays a central role in facilitating communication, alongside strategic communication practices tailored to intercultural contexts. Additionally, the study highlights the significance of sustainable development goals in guiding the formulation of practical communication models, with an emphasis on preserving cultural diversity as a key aspect. Insights from a survey examining the relationship between sustainable values and interpersonal communication are integrated, offering practical implications for promoting effective intercultural dialogue. In conclusion, this research contributes theoretical insights and pragmatic strategies to advance intercultural communication for sustainable development, underscoring the imperative of cultural diversity preservation on a global scale.
Keywords: intercultural communication, interpersonal communication, sustainable development, cultural context, communicative space, language strategies, sustainable value perception, global communication dynamics