bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia
Authors: Torres-Diz Manuel , Reglero Clara , Falkenstein Catherine D. , Castro Annette , Hayer Katharina E. , Radens Caleb M. , Quesnel-Vallières Mathieu , Ang Zhiwei , Sehgal Priyanka , Li Marilyn M. , Barash Yoseph , Tasian Sarah K. , Ferrando Adolfo , Thomas-Tikhonenko Andrei 
Published: August 2024

Abstract
Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer–related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B-ALL patients, suggesting additional mechanisms of resistance. By mining RNA sequencing datasets of paired diagnostic/relapse pediatric B-ALL samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers of resistance to glucocorticoids, antifolates, and thiopurines. Most splicing variations represented cassette exon skipping, “poison” exon inclusion, and intron retention, phenocopying well-documented loss-of-function mutations. In contrast, relapse-associated AS of NT5C2 mRNA yielded an isoform with the functionally uncharacterized in-frame exon 6a. Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine resistance. Consistent with this finding, NT5C2ex6a and the R238W hotspot variant conferred comparable levels of resistance to 6-mercaptopurine in B-ALL cells both in vitro and in vivo. Furthermore, both NT5C2ex6a and the R238W variant induced collateral sensitivity to the inosine monophosphate dehydrogenase inhibitor mizoribine. These results ascribe to splicing perturbations an important role in chemotherapy resistance in relapsed B-ALL and suggest that inosine monophosphate dehydrogenase inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias.
Significance: Alternative splicing is a potent mechanism of acquired drug resistance in relapsed/refractory acute lymphoblastic leukemias that has diagnostic and therapeutic implications for patients who lack mutations in known chemoresistance genes.
The Interplay between Extracellular Matrix Remodeling and Cancer Therapeutics
Authors: Prakash Jai , Shaked Yuval 
Published: August 2024

Abstract
The extracellular matrix (ECM) is an abundant noncellular component of most solid tumors known to support tumor progression and metastasis. The interplay between the ECM and cancer therapeutics opens up new avenues in understanding cancer biology. While the ECM is known to protect the tumor from anticancer agents by serving as a biomechanical barrier, emerging studies show that various cancer therapies induce ECM remodeling, resulting in therapy resistance and tumor progression. This review discusses critical issues in this field including how the ECM influences treatment outcome, how cancer therapies affect ECM remodeling, and the challenges associated with targeting the ECM.
Significance: The intricate relationship between the extracellular matrix (ECM) and cancer therapeutics reveals novel insights into tumor biology and its effective treatment. While the ECM may protect tumors from anti-cancer agents, recent research highlights the paradoxical role of therapy-induced ECM remodeling in promoting treatment resistance and tumor progression. This review explores the key aspects of the interplay between ECM and cancer therapeutics.
Lung Cancer Adoptive Cell Therapy: Inspiring TIL ACT Comes Center Stage
Authors: Lotze Michael T. , Maeurer Markus , Quezada Sergio A. , Coukos George 
Published: August 2024

Summary:Schoenfeld and colleagues report, in this issue, a measurable objective response rate in 6/28 (21.4%) of patients with advanced non–small cell lung cancer treated with lifileucel, a cell therapy product based on autologous tumor-infiltrating lymphocytes (TIL). Extending solid evidence in advanced melanoma that led to FDA approval of lifileucel, this new evidence bodes well for treating patients with other common tumor histologies, justifying important efforts by a large number of academic and biotechnology companies engaged in improving the TIL process.See related article by Schoenfeld et al., p. 1389 (1).
Iron: The Secret Ingredient Breaking PARPi Resistance
Authors: Alborzinia Hamed , Friedmann Angeli José Pedro 
Published: August 2024

Summary:PARP inhibitors (PARPi) are used as a first-line treatment option for cancers with BRCA1/2 mutations, yet a significant number of patients show a limited response to these agents. In the present study, Lei and colleagues demonstrate that PARPi promote increased ferroptosis sensitivity and this can be exploited therapeutically to improve the response to PARPi, marking an important therapeutic concept to exploit ferroptosis-based strategies in clinical settings.See related article by Lei et al., p. 1476 (2).
Intramyocardial Sprouting Tip Cells Specify Coronary Arterialization
Authors: Cano Elena , Schwarzkopf Jennifer , Kanda Masatoshi , Lindberg Eric L. , Hollfinger Irene , Pogontke Cristina , Braeuning Caroline , Fischer Cornelius , Hübner Norbert , Gerhardt Holger 
Published: August 2024

BACKGROUND:
The elaborate patterning of coronary arteries critically supports the high metabolic activity of the beating heart. How coronary endothelial cells coordinate hierarchical vascular remodeling and achieve arteriovenous specification remains largely unknown. Understanding the molecular and cellular cues that pattern coronary arteries is crucial to develop innovative therapeutic strategies that restore functional perfusion within the ischemic heart.

METHODS:
Single-cell transcriptomics and histological validation were used to delineate heterogeneous transcriptional states of the developing and mature coronary endothelium with a focus on sprouting endothelium and arterial cell specification. Genetic lineage tracing and high-resolution 3-dimensional imaging were used to characterize the origin and mechanisms of coronary angiogenic sprouting, as well as to fate-map selective endothelial lineages. Integration of single-cell transcriptomic data from ischemic adult mouse hearts and human embryonic data served to assess the conservation of transcriptional states across development, disease, and species.

RESULTS:

We discover that coronary arteries originate from cells that have previously transitioned through a specific tip cell phenotype. We identify nonoverlapping intramyocardial and subepicardial tip cell populations with differential gene expression profiles and regulatory pathways.
Esm1
-lineage tracing confirmed that intramyocardial tip cells selectively contribute to coronary arteries and endocardial tunnels, but not veins. Notably, prearterial cells are detected from development stages to adulthood, increasingly in response to ischemic injury, and in human embryos, suggesting that tip cell-to-artery specification is a conserved mechanism.

CONCLUSIONS:
A tip cell-to-artery specification mechanism drives arterialization of the intramyocardial plexus and endocardial tunnels throughout life and is reactivated upon ischemic injury. Differential sprouting programs govern the formation and specification of the venous and arterial coronary plexus.
Humans Learn Language from Situated Communicative Interactions. What about Machines?
Authors: Beuls Katrien , Van Eecke Paul 
Published: August 2024

Abstract
Humans acquire their native languages by taking part in communicative interactions with their caregivers. These interactions are meaningful, intentional, and situated in their everyday environment. The situated and communicative nature of the interactions is essential to the language acquisition process, as language learners depend on clues provided by the communicative environment to make sense of the utterances they perceive. As such, the linguistic knowledge they build up is rooted in linguistic forms, their meaning, and their communicative function. When it comes to machines, the situated, communicative, and interactional aspects of language learning are often passed over. This applies in particular to today’s large language models (LLMs), where the input is predominantly text-based, and where the distribution of character groups or words serves as a basis for modeling the meaning of linguistic expressions. In this article, we argue that this design choice lies at the root of a number of important limitations, in particular regarding the data hungriness of the models, their limited ability to perform human-like logical and pragmatic reasoning, and their susceptibility to biases. At the same time, we make a case for an alternative approach that models how artificial agents can acquire linguistic structures by participating in situated communicative interactions. Through a selection of experiments, we show how the linguistic knowledge that is captured in the resulting models is of a fundamentally different nature than the knowledge captured by LLMs and argue that this change of perspective provides a promising path towards more human-like language processing in machines.
Reliability of task-based fMRI in the dorsal horn of the human spinal cord
Authors: Dabbagh Alice , Horn Ulrike , Kaptan Merve , Mildner Toralf , Müller Roland , Lepsien Jöran , Weiskopf Nikolaus , Brooks Jonathan C.W. , Finsterbusch Jürgen , Eippert Falk 
Published: August 2024

Abstract
The application of functional magnetic resonance imaging (fMRI) to the human spinal cord is still a relatively small field of research and faces many challenges. Here we aimed to probe the limitations of task-based spinal fMRI at 3T by investigating the reliability of spinal cord blood oxygen level dependent (BOLD) responses to repeated nociceptive stimulation across 2 consecutive days in 40 healthy volunteers. We assessed the test–retest reliability of subjective ratings, autonomic responses, and spinal cord BOLD responses to short heat-pain stimuli (1 s duration) using the intraclass correlation coefficient (ICC). At the group level, we observed robust autonomic responses as well as spatially specific spinal cord BOLD responses at the expected location, but no spatial overlap in BOLD response patterns across days. While autonomic indicators of pain processing showed good-to-excellent reliability, both β-estimates and z-scores of task-related BOLD responses showed poor reliability across days in the target region (gray matter of the ipsilateral dorsal horn). When taking into account the sensitivity of gradient-echo echo planar imaging (GE-EPI) to draining vein signals by including the venous plexus in the analysis, we observed BOLD responses with fair reliability across days. Taken together, these results demonstrate that heat-pain stimuli as short as 1 s are able to evoke a robust and spatially specific BOLD response, which is, however, strongly variable within participants across time, resulting in low reliability in the dorsal horn gray matter. Further improvements in data acquisition and analysis techniques are thus necessary before event-related spinal cord fMRI as used here can be reliably employed in longitudinal designs or clinical settings.
Cybercrime Investigation and Prosecution in Nigeria: Bridging the Gaps
Authors: Nwafor Ifeoma E. 
Published: August 2024

Abstract
The investigatory framework of cybercrime is as essential as the legal and institutional framework governing cybercrime. This article argues that an effective investigation process is fundamental to the effective prosecution of cybercrime offences. Cybercrime investigation involves digital forensics, intelligence gathering, lawful interception, and use of communication data and internet networks. At its core, cybercrime investigation necessitates a comprehensive cybercrime investigation framework backed by a legal framework that ensures effective evidence collection, preservation, and analysis. This article evaluates the cybercrime investigation structure in Nigeria and highlights the gaps in Nigeria’s regulatory framework. It identifies the challenges that hinder Nigeria’s successful investigation and prosecution of cybercrime offences. The study adopts a comparative methodology by juxtaposing cybercrime investigation in Nigeria with the law and practice in the United Kingdom (UK). The UK has a robust cybercrime investigation framework, strengthened by its Cyber Security Strategy 2022. The findings show that, unlike the UK’s Regulation of Investigatory Powers Act, 2000 and the Investigatory Powers Act, 2016, the Nigerian Cybercrimes (Amendment) Act, 2024, the Administration of Criminal Justice Act, 2015 and other laws, are silent on essential investigatory initiatives, steps and specialised powers. The study proposes a practical cybercrime investigation framework to implement Nigeria’s effective prosecution of cybercrime offences.
The 30% Gender Quota Law in Sierra Leone: A Game Changer for Women’s Access to Parliament?
Authors: Lihiru Victoria Melkisedeck 
Published: August 2024

Abstract
The June 2023 elections in Sierra Leone occurred against the backdrop of amendments to the Public Elections Act (pea), the enactment of the Gender Equality and Women’s Empowerment Act (gewe), and a switch from the First Past the Post (fptp) electoral system to the Proportional Representation (pr) electoral system. For the first time in Sierra Leone’s history, law reforms, among other things, introduced a 30% gender quota rule for parliamentary and councillorship seats. After the 2023 elections, women won 41 out of the 135 elected parliamentary seats, increasing the percentage of women parliamentarians from 12.32% in the 2018 elections to 30.37%. Despite the increase, there have been concerns about the overall effectiveness of the gender quota rule in facilitating women’s access to parliamentary seats. The gender quota rule is set below 50%, is not accompanied by the candidates’ ranking order, does not apply in the election of 14 paramount chiefs, and operates within poor data desegregation of the candidates. This article highlights the required reforms to address the identified legal challenges to facilitate women’s equal access to representation in Sierra Leone’s Parliament.
Jane Addams and the Limits of Sympathy. Failures, Corrections, and Lessons to be Learned
Authors: Mattarollo Livio , Santarelli Matteo 
Published: August 2024

Abstract
Jane Addams takes sympathetic knowledge as a key concept for her moral and political philosophy. However, regarding the classical objections to sympathy as a foundation for morality and democracy, some theoretical remarks are still needed. In this article we aim at showing that the main problem is not due to the absence but to the qualitative import of sympathy in democratic societies. To achieve this goal, we firstly consider Addams’ idea of sympathetic knowledge in light of the influence of social evolutionary theorizing and her distinction between individual and social ethics. Secondly, we analyze the 1894 Pullman strike and the “newsboy” case, and we argue that failures in sympathy may be corrected by a horizontal process. As a result, we consider them not only as failures but mainly as lessons to be learned towards democracy as a rule of living.
L1 Attrition and Repair in Remnant Language Islands
Authors: Schreiber Henning 
Published: August 2024

Abstract
Sociolinguistically, isolation can be seen as a speech-community event which is commonly the result of migration, e.g., if speakers from a larger speech community migrate into a language island, leading to contact-induced variation. Another type of language island results from extensive language shift when a formerly larger language area shrinks to a remnant speech community, an enclave. The literature shows, however, that in both cases ethno-linguistic vitality is precarious, and that the impact of language contact is observable at all levels. Nevertheless, the question arises as to whether contact-induced variation is sociolinguistically distinct from variation in an enclave island. The paper describes the enregisterment of semi-speech and repair strategies similar to ‘L1 creolisation’ in an endangered Eastern Mande language, Kyanga, spoken on the border of Benin/Nigeria.
Stealthily Breaching Dikes and the Bare Sticks Substatute: Notes on Some Legal Aspects of River Hydraulics in Late Imperial China
Authors: Amelung Iwo 
Published: August 2024

Abstract
Human-induced breaches in the dikes of the major river systems were a common phenomenon in late imperial China. The article examines cases mainly related to the Yellow River and how these cases were dealt with on the basis of the legal code.
While the extensive coverage of such cases in legal documents is an important reminder of the high degree of attention that the state paid to hydraulic installations, the phenomenon also needs to be understood as an manifestation of societal conflicts resulting from the pressures of the demographic and environmental developments of China in the late imperial period.
Articulating the Pacific Economy: Chinese Mercury, American Silver, and Californian Sea Otters
Authors: Giráldez Arturo , Richard Analiese 
Published: August 2024

Abstract
Among Hans Ulrich Vogel’s important contributions to Chinese and world history has been his work on the outsized influence China exercised in the early history of globalization. In this brief article, we pay tribute to his careful research and deep insights by describing the interconnected circuits of exchange of three commodities – mercury, silver, and sea otter pelts – through which the early Pacific economy was articulated and transformed. Following Professor Vogel’s lead, we explain how the Chinese demand that drove these exchanges fueled competitive economic expansion of European powers in the Pacific, setting in motion political, social, ecological, and economic patterns whose influence endures into the present.
Are Our Climate Data Fit for Your Purpose?
Authors: Dee Dick , Obregon André , Buontempo Carlo 
Published: August 2024

Abstract
This paper describes the vision and objectives for evaluation and quality control of datasets available on the Climate Data Store (CDS) of the Copernicus Climate Change Service (C3S). The CDS is a cloud service providing reliable, open, and free access to climate datasets from many different sources, including observations and derived climate data records, global and regional reanalysis products, and output from global and regional climate models. CDS data and information are widely used to monitor climate change, for policy development, environmental impact studies, business plans, public awareness, and many other purposes. CDS users include policymakers, technical consultants, and data scientists who are climate literate but not necessarily specialized in climate science. A key objective for C3S is to simplify data discovery and access and to ensure that all information provided is fit for purpose. The role of evaluation and quality control is to generate useful statements about the technical and scientific quality of the datasets available on the CDS, presented in a form that can be mapped directly to user requirements associated with specific application contexts. The ambition is to enable users to select, locate, access, and process climate data that are fit for purpose, simply by expressing their requirements in their own words.
The Influence of Caribbean Current Eddies on Coastal Circulation in the Southwest Caribbean Sea
Authors: Kastner S. E. , Pawlak G. , Giddings S. N. , Adelson Anne E. , Collin R. , Davis K. A. 
Published: August 2024

Abstract
Westward-propagating Caribbean Current eddies modify the volume-integrated potential vorticity (PV) balance in the western Caribbean Sea, influencing the circulation of the Panamá–Colombia Gyre (PCG) and coastal currents hundreds of kilometers to the south of the eddies’ mean trajectory. Using 22 years of output from the Hybrid Coordinate Ocean Model, we apply a volume-integrated eddy phase-averaged 1.5-layer PV balance, showing that PV fluxes into the PCG region are balanced by frictional PV dissipation represented by linear drag along the coastline. Coastal currents in the PCG region vary by a factor of 2 in phase with the passage of a Caribbean Current eddy over the 116-day average eddy period. Flow separation at the Isthmus of Panamá results in a vortex shed from the Darien Gulf, which slows the coastal currents in the gyre region from their maximum during eddy events. An annual ensemble average PV balance in the gyre region shows that the mean PV influx to this region is higher from August to October. Correspondingly, the range of coastal currents in the gyre region over an eddy event is modestly influenced by the PV influx magnitude. Eddy-influenced reversals in the coastal current can occur between November and July at Bocas del Toro and year-round at Colón. Such coastal current reversals are important for the alongshore transport of larvae, freshwater, and chemical tracers.
Pain From a Distance: Can Third-Person Self-Talk Mitigate Pain Sensitivity and Pain Related Distress During Experimentally Induced Pain?
Authors: Gunnarsson Helena , Agerström Jens 
Published: August 2024

Pain is self-immersive, leading to a narrow, egocentric focus on the self in the here and now. Preliminary evidence suggests that distancing oneself from the pain can reduce experimentally induced pain. The primary aim of this experimental study was to examine whether a hitherto unexplored, simple self-distancing strategy – “third-person self-talk” – has an analgesic effect on physiological and psychological pain variables. Participants ( N = 292) were randomly assigned to one of four conditions (third-person self-talk, first-person self-talk, and two control conditions). Pain was induced with a cold pressor apparatus and pain tolerance, pain intensity, negative affect and blood pressure were measured for each group. While in pain, participants engaged in strategic self-talk aided by cue-cards. Data were analyzed with univariate planned comparisons. Few significant differences emerged for the third-person self-talk versus the other conditions. It is concluded that third-person self-talk does not seem to have a meaningful effect on physiological and psychological pain variables, although a small effect size could not be ruled out. Practical implications are discussed. The study was registered at ClinicalTrials.gov with the ClinicalTrials.gov ID NCT05511857.
An Innovative Approach to the Psychology Capstone Course
Authors: Bitz Kristi L. , Hair Rodney 
Published: August 2024

Background While capstone courses are popular among psychology programs, the capstone course design at a small private Midwestern university seems less conventional. Objective Along with meeting five course objectives, the course addresses understanding vocation, identifying academic and career strengths and weaknesses, identifying talents and gifts, articulating goals, defining servant leadership, knowing what it takes to persist in college and what career to pursue, and understanding purpose and calling. Method Students completed a 10-item questionnaire addressing the aforementioned items on the first and last days of class during four consecutive fall offerings of the Senior Capstone in Psychology course. Results Analysis of pre and posttest data revealed high confidence in positive change from the beginning to the end of the semester on every item measured. Conclusion Significant perceived student growth among each of the 10 questionnaire items was evident. Teaching Implications Institutions that wish to aid in the development of students related to vocation, servant leadership, and calling may want to consider the course design.