bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mississippi, USA's local landscapes: geoheritage value and educational benefits within college palaeontology classrooms
Authors: Clary Renee M. 
Published: January 2024

Abstract
In Mississippi, USA, exposures of fossiliferous Cretaceous and Paleogene strata contributed to geological investigations for more than 200 years. Since 2012, four Mississippi fossiliferous field sites were regularly integrated within university palaeontology classrooms, with community engaged learning (CEL) introduced in 2018. Through CEL projects, the students assisted local organizations with optimizing and/or protecting local fossiliferous sites. Analysis of student surveys demonstrated that students were overwhelmingly positive toward local field sites and CEL inclusion in the palaeontology courses. Students acknowledged ‘real-world’ interdisciplinary CEL experiences moved them beyond the palaeontology content and made them stakeholders in modern issues. While these four sites contain landscapes that qualify as local geoheritage sites because of their educational and potential geotourism value, only one site, W.M. Browning Cretaceous Fossil Park, is preserved for future generations. The other sites (Blue Springs, Osborn Prairie, Smith County) face challenges in their long-term sustainability.
Foretinib Is Effective in Acute Myeloid Leukemia by Inhibiting FLT3 and Overcoming Secondary Mutations That Drive Resistance to Quizartinib and Gilteritinib
Authors: Wang Peihong , Zhang Yvyin , Xiang Rufang , Yang Jie , Xu Yanli , Deng Tingfen , Zhou Wei , Wang Caixia , Xiao Xinhua , Wang Shunqing 
Published: January 2024

Abstract

FLT3 internal tandem duplication (FLT3-ITD) mutations are one of the most prevalent somatic alterations associated with poor prognosis in patients with acute myeloid leukemia (AML). The clinically approved FLT3 kinase inhibitors gilteritinib and quizartinib improve the survival of patients with AML with FLT3-ITD mutations, but their long-term efficacy is limited by acquisition of secondary drug-resistant mutations. In this study, we conducted virtual screening of a library of 60,411 small molecules and identified foretinib as a potent FLT3 inhibitor. An integrated analysis of the BeatAML database showed that foretinib had a lower IC50 value than other existing FLT3 inhibitors in patients with FLT3-ITD AML. Foretinib directly bound to FLT3 and effectively inhibited FLT3 signaling. Foretinib potently inhibited proliferation and promoted apoptosis in human AML cell lines and primary AML cells with FLT3-ITD mutations. Foretinib also significantly extended the survival of mice bearing cell-derived and patient-derived FLT3-ITD xenografts, exhibiting stronger efficacy than clinically approved FLT3 inhibitors in treating FLT3-ITD AML. Moreover, foretinib showed potent activity against secondary mutations of FLT3-ITD that confer resistance to quizartinib and gilteritinib. These findings support the potential of foretinib for treating patients with AML with FLT3-ITD mutations, especially for those carrying secondary mutations after treatment failure with other FLT3 inhibitors.

Significance:
Foretinib exhibits superior efficacy to approved drugs in AML with FLT3-ITD mutations and retains activity in AML with secondary FLT3 mutations that mediate resistance to clinical FLT3 inhibitors.
Inhibition of Ephrin B2 Reverse Signaling Abolishes Multiple Myeloma Pathogenesis
Authors: Sasine Joshua P. , Kozlova Natalia Y. , Valicente Lisa , Dukov Jennifer , Tran Dana H. , Himburg Heather A. , Kumar Sanjeev , Khorsandi Sarah , Chan Aldi , Grohe Samantha , Li Michelle , Kan Jenny , Sehl Mary E. , Schiller Gary J. , Reinhardt Bryanna , Singh Brijesh Kumar , Ho Ritchie , Yue Peibin , Pasquale Elena B. , Chute John P. 
Published: January 2024

Abstract

Bone marrow vascular endothelial cells (BM EC) regulate multiple myeloma pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating multiple myeloma. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote multiple myeloma growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in multiple myeloma–supportive ECs. Expression of ephrin B2 (EFNB2), the binding partner for EPHB1 and EPHB4, was significantly increased in multiple myeloma cells. Silencing EPHB1 or EPHB4 in ECs suppressed multiple myeloma growth in coculture. Similarly, loss of EFNB2 in multiple myeloma cells blocked multiple myeloma proliferation and survival in vitro, abrogated multiple myeloma engraftment in immune-deficient mice, and increased multiple myeloma sensitivity to chemotherapy. Administration of an EFNB2-targeted single-chain variable fragment also suppressed multiple myeloma growth in vivo. In contrast, overexpression of EFNB2 in multiple myeloma cells increased STAT5 activation, increased multiple myeloma cell survival and proliferation, and decreased multiple myeloma sensitivity to chemotherapy. Conversely, expression of mutant EFNB2 lacking reverse signaling capacity in multiple myeloma cells increased multiple myeloma cell death and sensitivity to chemotherapy and abolished multiple myeloma growth in vivo. Complementary analysis of multiple myeloma patient data revealed that increased EFNB2 expression is associated with adverse-risk disease and decreased survival. This study suggests that EFNB2 reverse signaling controls multiple myeloma pathogenesis and can be therapeutically targeted to improve multiple myeloma outcomes.

Significance:
Ephrin B2 reverse signaling mediated by endothelial cells directly regulates multiple myeloma progression and treatment resistance, which can be overcome through targeted inhibition of ephrin B2 to abolish myeloma.
Post-translational Modification of PD-1: Potential Targets for Cancer Immunotherapy
Authors: Lee Te-An , Tsai En-Yun , Liu Shou-Hou , Hsu Hung Shih-Duo , Chang Shing-Jyh , Chao Chi-Hong , Lai Yun-Ju , Yamaguchi Hirohito , Li Chia-Wei 
Published: January 2024

Abstract
Activation of effector T cells leads to upregulation of PD-1, which can inhibit T-cell activity following engagement with its ligand PD-L1. Post-translational modifications (PTM), including glycosylation, phosphorylation, ubiquitination, and palmitoylation, play a significant role in regulating PD-1 protein stability, localization, and interprotein interactions. Targeting PTM of PD-1 in T cells has emerged as a potential strategy to overcome PD-1–mediated immunosuppression in cancer and enhances antitumor immunity. The regulatory signaling pathways that induce PTM of PD-1 can be suppressed with small-molecule inhibitors, and mAbs can directly target PD-1 PTMs. Preliminary outcomes from exploratory studies suggest that focusing on the PTM of PD-1 has strong therapeutic potential and can enhance the response to anti-PD-1.
Rural–Urban Differences in Sun Exposure and Protection Behaviors in the United States
Authors: Dona Allison C. , Jewett Patricia I. , Henning-Smith Carrie , Ahmed Rehana L. , Wei Maria L. , Lazovich DeAnn , Vogel Rachel I. 
Published: January 2024

Abstract

Background:
Evidence regarding whether rural residence is a risk factor for skin cancer is mixed. We compared sun exposure and protection behaviors between rural and urban residents by ethno-racial group in the United States.

Methods:
We analyzed data from three (2013–2018) National Health and Nutrition Examination Survey cycles. We compared self-reported sun exposure and protection measures (sunburn, time spent outside, sunscreen use, wearing long sleeves, staying in shade) by rural–urban residential status using survey-weighted logistic regression models stratified by ethno-racial group, adjusting for age, sex, income, education, body mass index, and smoking.

Results:
Hispanic rural versus urban residents more often reported sunburns in the past year [41.6% vs. 31.2%, adjusted OR (aOR): 1.46 (1.15–1.86)]. White rural versus urban residents more often spent 2+ hours outside on workdays [42.9% vs. 29.1%, aOR: 1.60 (1.27–2.01)] and non-workdays [72.2% vs. 64.8%, aOR: 1.45 (1.12–1.88)] and less often used sunscreen [26.0% vs. 35.1%, aOR: 0.74 (0.59–0.93)] and stayed in the shade [21.7% vs. 26.7%, aOR: 0.72 (0.57–0.89)]. Black rural versus urban residents stayed in the shade less often [31.6% vs. 43.9%, aOR: 0.60 (0.39–0.91)] but less often spent 2+ hours outside on non-workdays [47.6% vs. 56.8%, aOR: 0.67 (0.51–0.90)].

Conclusions:
Across all ethno-racial groups included, rural residents reported greater sun risk behaviors than urban residents, with some nuances by ethno-racial identity, suggesting rural residence is a potential risk factor for skin cancer.

Impact:
Sun protection promotion programs should consider rural–urban settings while also accounting for ethno-racial identities.
Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study
Authors: Ahn Daniel H. , Barzi Afsaneh , Ridinger Maya , Samuëlsz Errin , Subramanian Ramanand A. , Croucher Peter J.P. , Smeal Tod , Kabbinavar Fairooz F. , Lenz Heinz-Josef 
Published: January 2024

Abstract

Purpose:
Onvansertib is a highly specific inhibitor of polo-like kinase 1 (PLK1), with demonstrated safety in solid tumors. We evaluated, preclinically and clinically, the potential of onvansertib in combination with chemotherapy as a therapeutic option for KRAS-mutant colorectal cancer.

Patients and Methods:
Preclinical activity of onvansertib was assessed (i) in vitro in KRAS wild-type and -mutant isogenic colorectal cancer cells and (ii) in vivo, in combination with irinotecan, in a KRAS-mutant xenograft model. Clinically, a phase Ib trial was conducted to investigate onvansertib at doses 12, 15, and 18 mg/m2 (days 1–5 and 14–19 of a 28-day cycle) in combination with FOLFIRI/bevacizumab (days 1 and 15) in patients with KRAS-mutant metastatic colorectal cancer who had prior oxaliplatin exposure. Safety, efficacy, and changes in circulating tumor DNA (ctDNA) were assessed.

Results:
In preclinical models, onvansertib displayed superior activity in KRAS-mutant than wild-type isogenic colorectal cancer cells and demonstrated potent antitumor activity in combination with irinotecan in vivo. Eighteen patients enrolled in the phase Ib study. Onvansertib recommended phase II dose was established at 15 mg/m2. Grade 3 and 4 adverse events (AE) represented 15% of all treatment-related AEs, with neutropenia being the most common. Partial responses were observed in 44% of patients, with a median duration of response of 9.5 months. Early ctDNA dynamics were predictive of treatment efficacy.

Conclusions:
Onvansertib combined with FOLIFRI/bevacizumab exhibited manageable safety and promising efficacy in second-line treatment of patients with KRAS-mutant metastatic colorectal cancer. Further exploration of this combination therapy is ongoing.
See related commentary by Stebbing and Bullock, p. 2005
Mass Spectrometry–Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer
Authors: Huang Yufeng , Gong Ming , Chen Hongmin , Deng Chuangzhong , Zhu Xiaojun , Lin Jiaming , Huang Anfei , Xu Yanyang , Tai Yi , Song Guohui , Xu Huaiyuan , Hu Jinxin , Feng Huixiong , Tang Qinglian , Lu Jinchang , Wang Jin 
Published: January 2024

Abstract

Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry–based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell–dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM.

Implications:
SB9 as a therapeutic target for LCBM.
Conhecer (n)os sonhos: uma busca na Antropologia
Authors: Nascimento Maria Sampaio do , Creado Eliana S. J 
Published: January 2024

Escrever sobre os sonhos é desafiador. É acreditar no que não se vê, mas aguçar a curiosidade frente aos mistérios proporcionados pelas experiências oníricas. São dois os objetivos principais neste artigo: primeiro, refletir sobre o que alguns teóricos escreveram sobre sonhos, pondo em diálogo autores de etnologia indígena e estudos sobre religiões afro-brasileiras; segundo, por em diálogo relatos de sonhos em que relações entre humanos e não humanos foram fundamentais: de um lado, um parente falecido e uma cachorrinha; de outro, espíritos de Pretas Velhas. Os sonhos podem ser uma das vias para, ao mesmo tempo, compreender relações e acontecimentos (d)e perdas, bem como a existência de outros mundos a entrelaçar o individual e o coletivo, o humano e o não humano.
Sex Differences in the Association of Age at Hypertension Diagnosis With Brain Structure
Authors: Kaur Amanpreet , Angarita Fonseca Adriana , Lissaman Rikki , Behlouli Hassan , Rajah M. Natasha , Pilote Louise 
Published: January 2024

BACKGROUND:
Sex differences exist in the likelihood of cognitive decline. The age at hypertension diagnosis is a unique contributor to brain structural changes associated with cerebral small vessel disease. However, whether this relationship differs between sexes remains unclear. Therefore, our objective was to evaluate sex differences in the association between the age at hypertension diagnosis and cerebral small vessel disease–related brain structural changes.

METHODS:
We used data from the UK Biobank to select participants with a known age at hypertension diagnosis and brain magnetic resonance imaging (n=9430) and stratified them by sex and age at hypertension diagnosis. Control participants with magnetic resonance imaging scans but no hypertension were chosen at random matched by using propensity score matching. For morphological brain structural changes, generalized linear models were used while adjusting for other vascular risk factors. For the assessment of white matter microstructure, principal component analysis led to a reduction in the number of fractional anisotropy variables, followed by regression analysis with major principal components as outcomes.

RESULTS:
Males but not females with a younger age at hypertension diagnosis exhibited lower brain gray and white matter volume compared with normotensive controls. The volume of white matter hyperintensities was greater in both males and females with hypertension than normotensive controls, significantly higher in older females with hypertension. Compared with normotensive controls, white matter microstructural integrity was lower in individuals with hypertension, which became more prominent with increasing age.

CONCLUSIONS:
Our study demonstrates that the effect of hypertension on cerebral small vessel disease–related brain structure differs by sex and by age at hypertension diagnosis.
Perceived Stress From Childhood to Adulthood and Cardiometabolic End Points in Young Adulthood: An 18‐Year Prospective Study
Authors: Guo Fangqi , Chen Xinci , Howland Steve , Danza Phoebe , Niu Zhongzheng , Gauderman W. James , Habre Rima , McConnell Rob , Yan Mingzhu , Whitfield Lora , Li Yanjie , Hodis Howard N. , Breton Carrie V. , Bastain Theresa M. , Farzan Shohreh F. 
Published: January 2024

Background
We investigated how childhood‐to‐adulthood perceived stress patterns predict adult cardiometabolic risk.

Methods and Results
This study included 276 participants from the Southern California Children's Health Study (2003–2014), and a follow‐up assessment (2018–2021). Perceived stress (Perceived Stress Scale) was initially reported by participants' parents for themselves during early childhood (mean age, 6.3 years), and later self‐reported during adolescence (13.3 years) and young adulthood (23.6 years). Participants were grouped into 4 stress patterns: consistently high, decreasing, increasing, and consistently low. Cardiometabolic risk was assessed in young adulthood by carotid artery intima‐media thickness, systolic and diastolic blood pressure, obesity, percent body fat, android/gynoid ratio, and glycated hemoglobin. A cardiometabolic risk score was generated by summing the clinically abnormal markers. Multivariable linear and logistic regression models were used to (1) examine the associations between Perceived Stress Scale at 3 time points and adult cardiometabolic risk, and (2) assess the impact of stress pattern on adult cardiometabolic risk. Findings suggested that in adulthood, higher Perceived Stress Scale score was associated with increased overall cardiometabolic risk (β=0.12 [95% CI, 0.01–0.22]), carotid artery intima‐media thickness (β=0.01 [95% CI, 0.0003–0.02]), systolic blood pressure (β=1.27 [95% CI, 0.09–2.45]), and diastolic blood pressure (β=0.94 [95% CI, 0.13–1.75]). Individuals with a consistently high adolescence‐to‐adulthood stress pattern had greater overall cardiometabolic risk (β=0.31 [95% CI, 0.02–0.60]), android/gynoid ratio (β=0.07 [95% CI, 0.02–0.13]), percent body fat (β=2.59 [95% CI, 0.01–5.17]), and greater odds of obesity (odds ratio, 5.57 [95% CI, 1.62–19.10]) in adulthood, compared with those with a consistently low Perceived Stress Scale score.

Conclusions
Consistently high perceived stress from adolescence to adulthood may contribute to greater cardiometabolic risk in young adulthood.
Methods for decoding cortical gradients of functional connectivity
Authors: Peraza Julio A. , Salo Taylor , Riedel Michael C. , Bottenhorn Katherine L. , Poline Jean-Baptiste , Dockès Jérôme , Kent James D. , Bartley Jessica E. , Flannery Jessica S. , Hill-Bowen Lauren D. , Lobo Rosario Pintos , Poudel Ranjita , Ray Kimberly L. , Robinson Jennifer L. , Laird Robert W. , Sutherland Matthew T. , de la Vega Alejandro , Laird Angela R. 
Published: January 2024

AbstractMacroscale gradients have emerged as a central principle for understanding functional brain organization. Previous studies have demonstrated that a principal gradient of connectivity in the human brain exists, with unimodal primary sensorimotor regions situated at one end and transmodal regions associated with the default mode network and representative of abstract functioning at the other. The functional significance and interpretation of macroscale gradients remains a central topic of discussion in the neuroimaging community, with some studies demonstrating that gradients may be described using meta-analytic functional decoding techniques. However, additional methodological development is necessary to fully leverage available meta-analytic methods and resources and quantitatively evaluate their relative performance. Here, we conducted a comprehensive series of analyses to investigate and improve the framework of data-driven, meta-analytic methods, thereby establishing a principled approach for gradient segmentation and functional decoding. We found that a two-segment solution determined by a k-means segmentation approach and an LDA-based meta-analysis combined with the NeuroQuery database was the optimal combination of methods for decoding functional connectivity gradients. Finally, we proposed a method for decoding additional components of the gradient decomposition. The current work aims to provide recommendations on best practices and flexible methods for gradient-based functional decoding of fMRI data.
Expectation modifies the representational fidelity of complex visual objects
Authors: Moore Margaret Jane , Robinson Amanda K. , Mattingley Jason B. 
Published: January 2024

Abstract
Prediction has been shown to play a fundamental role in facilitating efficient perception of simple visual features such as orientation and motion, but it remains unclear whether expectations modulate neural representations of more complex stimuli. Here, we addressed this issue by characterising patterns of brain activity evoked by two-dimensional images of familiar, real-world objects which were either expected or unexpected based on a preceding cue. Participants (n=30) viewed stimuli in rapid serial visual presentation (RSVP) streams which contained both high-fidelity and degraded (diffeomorphically warped) object images. Multivariate pattern analyses of electroencephalography (EEG) data were used to quantify and compare the degree of information represented in neural activity when stimuli were random (unpredictable), expected, or unexpected. Degraded images elicited reduced representational fidelity relative to high-fidelity images. However, degraded images were represented with improved fidelity when they were presented in expected relative to random sequence positions; and stimuli in unexpected sequence positions yielded reduced representational fidelity relative to random presentations. Most notably, neural responses to unexpected stimuli contained information pertaining to the expected (but not presented) stimulus. Debriefing at the conclusion of the experiment revealed that participants were not aware of the relationship between cue and target stimuli within the RSVP streams, suggesting that the differences in stimulus decoding between conditions arose in the absence of explicit predictive knowledge. Our findings extend fundamental understanding of how the brain detects and employs predictive relationships to modulate high-level visual perception.
The Efficacy of the Development Studies Programme in Zimbabwe’s Development Work
Authors: Muzorewa Terence Tapiwa , Sillah Ramphal , Chibanda Tawanda William 
Published: January 2024

Abstract
The article analyses the impact of the development studies (DS) programme at Zimbabwean higher education institutions on development work in Zimbabwe. It describes how development studies became one of the most popular subjects in the humanities, offered by more than 10 universities and colleges in Zimbabwe. More than two decades later, there is convincing evidence that the programme’s influence on the development sector in Zimbabwe is diminishing. The article contends that the programme has been essential in sparking policy debates and incubating development theory among students and academics. However, the discipline has provided little in terms of actual practice and expertise in development work and community implementation. Therefore, development studies in Zimbabwe is an academic discipline with limited relevance to community development on the ground. This research is qualitative in nature. Qualitative data collected using purposive sampling is used to illustrate the rise of the discipline and its disparate effects on development activities in Zimbabwe. The article recommends a revision of the DS curriculum so that it fits the practical requirements for development work in Zimbabwe.