bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)
Authors: Hashimoto Tadayoshi , Tsukada Yuichiro , Ito Masaaki , Kanato Keisuke , Mizusawa Junki , Fukuda Haruhiko , Tsukamoto Shunsuke , Takashima Atsuo , Kanemitsu Yukihide 
Published: August 2023

IntroductionIn locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers. Therefore, we have launched a multi-institutional prospective observational study of ctDNA for MRD detection in conjunction with JCOG1801, a randomised, controlled phase III trial evaluating the efficacy of preoperative chemoradiotherapy (pre-CRT) compared with up-front surgery for LRRC (jRCTs031190076,NCT04288999).Methods and analysisJCOG1801A1 is the first correlative study that assesses ctDNA in LRRC patients enrolled in JCOG1801. Patients randomised to up-front surgery will provide whole blood samples at three time points (prior to surgery, after surgery and after postoperative chemotherapy); those to pre-CRT will provide at five time points (prior to pre-CRT, after pre-CRT, prior to surgery, after surgery and after postoperative chemotherapy). Cell-free DNA will be extracted from plasma and analysed by Guardant Reveal, a tumour tissue–agnostic assay that assesses both genomic alterations and methylation patterns to determine the presence or absence of ctDNA. We will compare the prognosis and treatment response of patients according to their ctDNA status after surgery and at other time points.Ethics and disseminationThe study protocol received approval from the Institutional Review Board of National Cancer Center Hospital East on behalf of the participating institutions in February 2023. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent will be obtained from all eligible patients prior to registration.
Multimodal molecular landscape of response to Y90-resin microsphere radioembolization followed by nivolumab for advanced hepatocellular carcinoma
Authors: Kaya Neslihan Arife , Tai David , Lim Xinru , Lim Jia Qi , Lau Mai Chan , Goh Denise , Phua Cheryl Zi Jin , Wee Felicia Yu Ting , Joseph Craig Ryan , Lim Jeffrey Chun Tatt , Neo Zhen Wei , Ye Jiangfeng , Cheung Lawrence , Lee Joycelyn , Loke Kelvin S H , Gogna Apoorva , Yao Fei , Lee May Yin , Shuen Timothy Wai Ho , Toh Han Chong , Hilmer Axel , Chan Yun Shen , Lim Tony Kiat-Hon , Tam Wai Leong , Choo Su Pin , Yeong Joe , Zhai Weiwei 
Published: August 2023

BackgroundCombination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown.MethodsBy collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial.ResultsWe found that higher tumor mutation burden,NCOR1mutations and higher expression of interferon gamma pathways occurred more frequently in responders. Meanwhile, non-responders tended to be enriched for a novel Asian-specific transcriptomic subtype (Kaya_P2) with a high frequency of chromosome 16 deletions and upregulated cell cycle pathways. Strikingly, unlike other cancer types, we did not observe any association between T-cell populations and treatment response, but tumors from responders had a higher proportion of CXCL9+/CXCR3+macrophages. Moreover, biomarkers discovered in previous immunotherapy trials were not predictive in the current cohort, suggesting a distinctive molecular landscape associated with differential responses to the combination therapy.ConclusionsThis study unraveled extensive molecular changes underlying distinctive responses to the novel treatment and pinpointed new directions for harnessing combination therapy in patients with advanced HCC.
Personalized neoantigen viro-immunotherapy platform for triple-negative breast cancer
Authors: Brito Baleeiro Renato , Liu Peng , Chard Dunmall Louisa S , Di Gioia Carmela , Nagano Ai , Cutmore Lauren , Wang Jun , Chelala Claude , Nyambura Lydon Wainaina , Walden Peter , Lemoine Nicholas , Wang Yaohe 
Published: August 2023

BackgroundTriple-negative breast cancer (TNBC) corresponds to approximately 20% of all breast tumors, with a high propensity for metastasis and a poor prognosis. Because TNBC displays a high mutational load compared with other breast cancer types, a neoantigen-based immunotherapy strategy could be effective. One major bottleneck in the development of a neoantigen-based vaccine for TNBC is the selection of the best targets, that is, tumor-specific neoantigens which are presented at the surface of tumor cells and capable of eliciting robust immune responses. In this study, we aimed to set up a platform for identification and delivery of immunogenic neoantigens in a vaccine regimen for TNBC using oncolytic vaccinia virus (VV).MethodsWe used bioinformatic tools and cell-based assays to identify immunogenic neoantigens in TNBC patients’ samples, human and murine cell lines. Immunogenicity of the neoantigens was tested in vitro (human) and ex vivo (murine) in T-cell assays. To assess the efficacy of our regimen, we used a preclinical model of TNBC where we treated tumor-bearing mice with neoantigens together with oncolytic VV and evaluated the effect on induction of neoantigen-specific CD8+T cells, tumor growth and survival.ResultsWe successfully identified immunogenic neoantigens and generated neoantigen-specific CD8+T cells capable of recognizing a human TNBC cell line expressing the mutated gene. Using a preclinical model of TNBC, we showed that our tumor-specific oncolytic VV was able to change the tumor microenvironment, attracting and maintaining mature cross-presenting CD8α+dendritic cells and effector T-cells. Moreover, when delivered in a prime/boost regimen together with oncolytic VV, long peptides encompassing neoantigens were able to induce neoantigen-specific CD8+T cells, slow tumor growth and increase survival.ConclusionsOur study provides a promising approach for the development of neoantigen-based immunotherapies for TNBC. By identifying immunogenic neoantigens and developing a delivery system through tumor-specific oncolytic VV, we have demonstrated that neoantigen-based vaccines could be effective in inducing neoantigen-specific CD8+T cells response with significant impact on tumor growth. Further studies are needed to determine the safety and efficacy of this approach in clinical trials.
Augmentation of flow diverter vessel wall apposition using the Comaneci device: case experience from a novel, off-label technique
Authors: Lin Li-Mei , Collard de Beaufort Jonathan , Wang Alice S , Campos Jessica K , Zarrin David A , Meyer Benjamen M , Colby Geoffrey P , Coon Alexander L 
Published: August 2023

BackgroundFlow diversion (FD) embolization of intracranial cerebral aneurysms is an increasingly common modality where treatment success depends on adequate vessel wall apposition of the device. This study aimed to investigate off-label use of the Comaneci device for augmenting vessel wall apposition in post-deployed flow diversion stents (FDS).MethodsOver a 20- month period, all FD cases for the treatment of internal carotid artery (ICA) aneurysms were reviewed. Cases in which the Comaneci device was used to augment vessel wall apposition were analyzed. Data including patient demographics, case characteristics, and procedural outcomes were collected and analyzed as counts.ResultsFrom a total of 74 ICA FD cases, the Comaneci device was used to improve vessel wall apposition in 22 cases (29.7%) . Of these cases, 91% were female with a mean patient age of 64.9±11.3 years, and an average aneurysm size of 4.5±2.5 mm. Comaneci device deployment and retrieval was successful in all (100%) cases, with an average fluoroscopy time of 27.3±7.8 min, an average contrast usage of 25.8±13.2 mL, and an average radiation exposure of 915.1±320.8 mGy. Only two cases (9%) required subsequent balloon angioplasty after Comaneci deployment to improve vessel wall apposition throughout the FDS.ConclusionOur experience with this technique demonstrates the feasibility of using the Comaneci device for augmentation of FDS vessel wall apposition with 100% success in the deployment and retrieval of the Comaneci device.
Planck length in classical and quantum Hamiltonian formulations of general relativity
Authors: Cremaschini Claudio 
Published: August 2023

AbstractThe physical meaning of the Planck length ($$\ell _{P}$$

ℓ
P

) is investigated in the framework of the unconstrained synchronous variational formulation of classical general relativity (GR). This theoretical setting permits the establishment of manifestly-covariant Lagrangian and Hamiltonian theories for the Einstein field equations of the continuum gravitational field. It is shown that such a formulation is distinguished by the existence of a novel variational contribution expressed by an infinite series summation of suitable 4-scalar terms in which the coupling coefficients are even powers of the Planck length. However, the requirement of realization of a classical GR Hamiltonian theory places stringent constraints on the admissible Planck-length power terms to be retained. In fact, excluding the trivial gauge constant, it is proved that only the $$O\left( \ell _{P}^{0}\right) $$

O

ℓ

P

0

contribution of the series is ultimately permitted, namely the unique one which is independent of $$\ell _{P}$$

ℓ
P

. Therefore, the Planck length is effectively not allowed to appear at the classical level for consistency with the Hamiltonian principle. This places important consequences on the mathematical establishment of the corresponding canonical quantum gravity theory, which is then found to be correct through $$O\left( \ell _{P}^{2}\right) $$

O

ℓ

P

2

. Additional implications concern the physical significance of related quantum momenta and their meaning in the semi-classical limit, as well as the role of the Planck length in the same quantum-gravity realm.
Spatio-temporal changes in racial segregation and diversity in large US cities from 1990 to 2020: a visual data analysis
Authors: Dmowska Anna , Stepinski Tomasz F. 
Published: August 2023

AbstractUrban populations in large US cities exhibit racial and ethnic diversity, yet they remain residentially segregated. The examination of temporal trends in segregation and diversity is crucial for sociologists and urban planners. In this study, we investigate the spatio-temporal changes in segregation and diversity across 61 major US cities, utilizing data from four US Censuses conducted between 1990 and 2020. Unlike previous studies, our approach relies on visual data analysis, enabling us to capture the overarching changes in racial coresidence during this period. We employ four distinct perspectives – geographical, temporal, groups evolution, and desegregation scale limit – to visualize and analyze the data. Geographical analysis uncovers a decrease in regional disparities in urban diversity and segregation since 1990, as urban racial integration extends beyond West Coast and Southwestern cities to encompass the entire US. Through temporal analysis, we observe a general trend of rapidly increasing diversity and gradual reduction in segregation, albeit with varying rates across different cities. Groups evolution analysis reveals that cities grouped based on their diversity and segregation metrics in 1990 follow the overall trend toward larger diversity and smaller segregation while preserving group’s coherence but not their distinctiveness. Finally, the desegregation scale limit perspective suggests that, on average, over the 1990 to 2020 period, the desegregation scale has started to subceed the lower limit of the census block. By employing these diverse analytical perspectives, our study provides a comprehensive understanding of the changes in racial segregation and diversity within US cities over the past three decades.
Towards hypergraph cognitive networks as feature-rich models of knowledge
Authors: Citraro Salvatore , De Deyne Simon , Stella Massimo , Rossetti Giulio 
Published: August 2023

AbstractConceptual associations influence how human memory is structured: Cognitive research indicates that similar concepts tend to be recalled one after another. Semantic network accounts provide a useful tool to understand how related concepts are retrieved from memory. However, most current network approaches use pairwise links to represent memory recall patterns (e.g. reading “airplane” makes one think of “air” and “pollution”, and this is represented by links “airplane”-“air” and “airplane”-“pollution”). Pairwise connections neglect higher-order associations, i.e. relationships between more than two concepts at a time. These higher-order interactions might covariate with (and thus contain information about) how similar concepts are along psycholinguistic dimensions like arousal, valence, familiarity, gender and others. We overcome these limits by introducing feature-rich cognitive hypergraphs as quantitative models of human memory where: (i) concepts recalled together can all engage in hyperlinks involving also more than two concepts at once (cognitive hypergraph aspect), and (ii) each concept is endowed with a vector of psycholinguistic features (feature-rich aspect). We build hypergraphs from word association data and use evaluation methods from machine learning features to predict concept concreteness. Since concepts with similar concreteness tend to cluster together in human memory, we expect to be able to leverage this structure. Using word association data from the Small World of Words dataset, we compared a pairwise network and a hypergraph with $N= 3586$
N
=
3586
concepts/nodes. Interpretable artificial intelligence models trained on (1) psycholinguistic features only, (2) pairwise-based feature aggregations, and on (3) hypergraph-based aggregations show significant differences between pairwise and hypergraph links. Specifically, our results show that higher-order and feature-rich hypergraph models contain richer information than pairwise networks leading to improved prediction of word concreteness. The relation with previous studies about conceptual clustering and compartmentalisation in associative knowledge and human memory are discussed.
Development and Stabilization of Value-Added Functional Drink Using Melon By-Product Agricultural Waste
Authors: Namet Saba , Khan Moazzam Rafiq , Aadil Rana Muhammad , Zia Muhammad Anjum 
Published: August 2023

Melon (Cucumis melo L.) is a widely grown horticulture crop in many parts of the world widely known for its nutritive properties. Processing of melon leads to the production of a wide range of natural end-user products and produces a significant quantity of underutilized by-products about 35%, which are made up of 3–7% of seeds and 25–44% of peels. The objective of the present research is the development of a value-added drink to effectively utilize melon by-products which are considered an excellent source of antioxidants and bioactive compounds using varying concentrations of peel and seed powder (5 and 10%) and their extracts (1 and 3%) alongside control treatment for comparison purpose. The prepared value-added drinks were stored for 3 months at

4
±
1

°C and analyzed at 15-day intervals for physicochemical characteristics, bioactive components, antioxidant indices, and sensorial evaluation. A significant (

p
<
0.05

) decrease in pH and an increase in acidity were noticed while total soluble sugars decreased slightly in all treatments throughout storage. In comparison to other drinks, value-added drink (

T

6

) prepared by incorporating 3% melon peel extract preserved total phenolic contents (

1.80
±
0.07

mg GAE/g), total flavonoid contents (

0.53
±
0.003

mg QE/g), DPPH (

53.23
±
0.07
%

), and FRAP (

3.85
±
0.08

μM FeSO4/g) at the end of storage and was effective in maintaining quality attribute, better retention of bioactive compounds, and longer shelf life due to higher antioxidant potential. In terms of sensorial scores,

T

4

(10% melon seed powder) was more acceptable and was effective in maintaining physicochemical attributes throughout storage. The conversion of such waste in developing innovative functional foods could maximize profit, reduce environmental issues, and improve the sustainability of food by incorporating food waste into the food chain. Such research investigation is aimed at allaying growing concerns about food waste by reusing rejected food by-products.
Integrative Genomic Analyses Identify LncRNA Regulatory Networks across Pediatric Leukemias and Solid Tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J. 
Published: August 2023

Abstract

Long noncoding RNAs (lncRNA) play an important role in gene regulation and contribute to tumorigenesis. While pan-cancer studies of lncRNA expression have been performed for adult malignancies, the lncRNA landscape across pediatric cancers remains largely uncharted. Here, we curated RNA sequencing data for 1,044 pediatric leukemia and extracranial solid tumors and integrated paired tumor whole genome sequencing and epigenetic data in relevant cell line models to explore lncRNA expression, regulation, and association with cancer. A total of 2,657 lncRNAs were robustly expressed across six pediatric cancers, including 1,142 exhibiting histotype-elevated expression. DNA copy number alterations contributed to lncRNA dysregulation at a proportion comparable to protein coding genes. Application of a multidimensional framework to identify and prioritize lncRNAs impacting gene networks revealed that lncRNAs dysregulated in pediatric cancer are associated with proliferation, metabolism, and DNA damage hallmarks. Analysis of upstream regulation via cell type–specific transcription factors further implicated distinct histotype-elevated and developmental lncRNAs. Integration of these analyses prioritized lncRNAs for experimental validation, and silencing of TBX2-AS1, the top-prioritized neuroblastoma-specific lncRNA, resulted in significant growth inhibition of neuroblastoma cells, confirming the computational predictions. Taken together, these data provide a comprehensive characterization of lncRNA regulation and function in pediatric cancers and pave the way for future mechanistic studies.

Significance:
Comprehensive characterization of lncRNAs in pediatric cancer leads to the identification of highly expressed lncRNAs across childhood cancers, annotation of lncRNAs showing histotype-specific elevated expression, and prediction of lncRNA gene regulatory networks.
Center-Sindh Relations in Pakistan after the 18th Amendment: Anatomy of Executive Federalism Under the PTI Government 2018–2022
Authors: Faiz Asma 
Published: August 2023

Abstract
This article examines the practice of Center-Province interaction in Pakistan by analyzing intergovernmental relations (IGR) between the federal (i.e., Center) and Sindh provincial governments. It focuses on the period when the Pakistan Tehreek-I-Insaaf (PTI) was in power at the Center (i.e., 2018–2022). Analyzing executive federalism and provincial governments is an understudied area of research in Pakistan. I provide an overview of the emerging literature on IGR and map out the institutional architecture of federalism in Pakistan. I pay special attention to platforms for managing Center-Province conflict, especially the Council of Common Interests (CCI). I then trace the trajectory of provincial autonomy in Sindh in the context of Pakistan’s centralized federation. My focus is on the impact of 2010 18th Amendment on regional power and the management of executive relations. I explore the critical issues of discord between the federal government of the PTI and the provincial one of the Pakistan Peoples Party (PPP) in Sindh. My analysis reflects continuing dominance of the Center and its linkage with party politics in the framework of executive interactions between governments at the two levels, characterized by a significant differential in their authority. I argue that constitutional devolution needs to be cushioned by a corresponding decentralization of powers to provinces like Sindh in the administrative and financial sectors.
Autonomy and equality: exploring the antinomy of modernity (if any)
Authors: Wagner Peter 
Published: August 2023

Abstract
The notion of modernity is mostly seen as closely connected with the concept of equality, along with freedom or autonomy, at least since the Enlightenment and the French Revolution. Recently, though, Johann Arnason cast doubts on this connection and even went as far as contemplating that equality might be the antinomy of autonomy. This article first discusses in detail Arnason’s reflections, in particular in the light of the relation between conceptual and historical analysis therein. It is shown that the suggested tension between autonomy and equality arises strongly once one assumes a comprehensive understanding of equality in which all aspects of the concept, which are otherwise often kept distinct, are included. In the second step, a historical sketch is meant to demonstrate that the political imaginary of modernity was based on such a comprehensive framework, but that any attempt at translating such a framework into institutions limited the scope of equality by setting boundaries for inclusion. Our present time is marked by the erosion of many such social boundaries, leading to a thin understanding of equality, while the simultaneous reaching of planetary boundaries turns equality into the receding horizon of modernity.