bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Boltzmann equation and equilibrium thermodynamics in Lorentz-violating theories
Authors: Potting Robertus 
Published: April 2023

AbstractIn this work, we adapt the foundations of relativistic kinetic theory and the Boltzmann equation to particles with Lorentz-violating dispersion relations. The latter are taken to be those associated to two commonly considered sets of coefficients in the minimal Standard-Model Extension. We treat both the cases of classical (Maxwell–Boltzmann) and quantum (Fermi–Dirac and Bose–Einstein) statistics. It is shown that with the appropriate definition of the entropy current, Boltzmann’s H-theorem continues to hold. We derive the equilibrium solutions and then identify the Lorentz-violating effects for various thermodynamic variables, as well as for Bose–Einstein condensation. Finally, a scenario with nonelastic collisions between multiple species of particles corresponding to chemical or nuclear reactions is considered.
Detecting topological phases in the square–octagon lattice with statistical methods
Authors: Wunderlich Paul , Ferrari Francesco , Valentí Roser 
Published: April 2023

AbstractElectronic systems living on Archimedean lattices such as kagome and square–octagon networks are presently being intensively discussed for the possible realization of topological insulating phases. Coining the most interesting electronic topological states in an unbiased way is however not straightforward due to the large parameter space of possible Hamiltonians. A possible approach to tackle this problem is provided by a recently developed statistical learning method (Mertz and Valentí in Phys Rev Res 3:013132, 2021. https://doi.org/10.1103/PhysRevResearch.3.013132), based on the analysis of a large data sets of randomized tight-binding Hamiltonians labeled with a topological index. In this work, we complement this technique by introducing a feature engineering approach which helps identifying polynomial combinations of Hamiltonian parameters that are associated with non-trivial topological states. As a showcase, we employ this method to investigate the possible topological phases that can manifest on the square–octagon lattice, focusing on the case in which the Fermi level of the system lies at a high-order van Hove singularity, in analogy to recent studies of topological phases on the kagome lattice at the van Hove filling.
The Lightweight Count System of Intensive Jellyfish Based on Deep Learning
Authors: Jin Yun , Zhang Haidong , Li Jiaxin , Bi Weihong 
Published: April 2023

The number of jellyfish outbreaks is on the rise around the world, and they have been considered a serious ecological disaster. As part of the emergency response plan for jellyfish disasters, in-situ detection research that can distinguish jellyfish species and quantities is urgently required to support accurate data collection. As a typical fully supervised regression task, counting is usually regarded as requiring a large number of labeled datasets in conventional counting methods. To treat counting as a few-shot regression task that is semi-supervised, a novel adaptation strategy based on deep learning is presented in this paper. The method combines the test image with several example objects from the test image and takes advantage of the strong similarities present in the test image and the example objects contained in the image. Effective counting can be achieved without training the target object. Prediction of the density map of the test image’s objects of interest is the objective of the test. This method has been shown to be more robust than the method of detection first and counting later, and its accuracy can exceed 95%.
Risk Factors and Trends for HPV-Associated Subsequent Malignant Neoplasms among Adolescent and Young Adult Cancer Survivors
Authors: Ou Judy Y. , Bennion Natalie , Parker Kellee , Fair Douglas , Hanson Heidi A. , Kepka Deanna , Warner Echo L. , Ramsay Joemy M. , Kaddas Heydon K. , Kirchhoff Anne C. 
Published: April 2023

Abstract

Background:
Subsequent malignant neoplasms (SMN; new cancers that arise after an original diagnosis) contribute to premature mortality among adolescent and young adult (AYA) cancer survivors. Because of the high population prevalence of human papillomavirus (HPV) infection, we identify demographic and clinical risk factors for HPV-associated SMNs (HPV-SMN) among AYA cancer survivors in the SEER-9 registries diagnosed from 1976 to 2015.

Methods:
Outcomes included any HPV-SMN, oropharyngeal-SMN, and cervical-SMN. Follow-up started 2 months after their original diagnosis. Standardized incidence ratios (SIR) compared risk between AYA survivors and general population. Age-period-cohort (APC) models examined trends over time. Fine and Gray's models identified therapy effects controlling for cancer and demographic confounders.

Results:
Of 374,408 survivors, 1,369 had an HPV-SMN, occurring on average 5 years after first cancer. Compared with the general population, AYA survivors had 70% increased risk for any HPV-SMN [95% confidence interval (CI), 1.61–1.79] and 117% for oropharyngeal-SMN (95% CI, 2.00–2.35); cervical-SMN risk was generally lower in survivors (SIR, 0.85; 95% CI, 0.76–0.95), but Hispanic AYA survivors had a 8.4 significant increase in cervical-SMN (SIR, 1.46; 95% CI, 1.01–2.06). AYAs first diagnosed with Kaposi sarcoma, leukemia, Hodgkin, and non-Hodgkin lymphoma had increased HPV-SMN risks compared with the general population. Oropharyngeal-SMN incidence declined over time in APC models. Chemotherapy and radiation were associated with any HPV-SMN among survivors with first HPV-related cancers, but not associated among survivors whose first cancers were not HPV-related.

Conclusions:
HPV-SMN in AYA survivors are driven by oropharyngeal cancers despite temporal declines in oropharyngeal-SMN. Hispanic survivors are at risk for cervical-SMN relative to the general population.

Impact:
Encouraging HPV vaccination and cervical and oral cancer screenings may reduce HPV-SMN burden among AYA survivors.
Dynamics of Sequence and Structural Cell-Free DNA Landscapes in Small-Cell Lung Cancer
Authors: Sivapalan Lavanya , Iams Wade T. , Belcaid Zineb , Scott Susan C. , Niknafs Noushin , Balan Archana , White James R. , Kopparapu Prasad , Cann Christopher , Landon Blair V. , Pereira Gavin , Velculescu Victor E. , Hann Christine L. , Lovly Christine M. , Anagnostou Valsamo 
Published: April 2023

Abstract

Purpose:
Patients with small-cell lung cancer (SCLC) have an exceptionally poor prognosis, calling for improved real-time noninvasive biomarkers of therapeutic response.

Experimental Design:
We performed targeted error-correction sequencing on 171 serial plasmas and matched white blood cell (WBC) DNA from 33 patients with metastatic SCLC who received treatment with chemotherapy (n = 16) or immunotherapy-containing (n = 17) regimens. Tumor-derived sequence alterations and plasma aneuploidy were evaluated serially and combined to assess changes in total cell-free tumor load (cfTL). Longitudinal dynamic changes in cfTL were monitored to determine circulating cell-free tumor DNA (ctDNA) molecular response during therapy.

Results:
Combined tiered analyses of tumor-derived sequence alterations and plasma aneuploidy allowed for the assessment of ctDNA molecular response in all patients. Patients classified as molecular responders (n = 9) displayed sustained elimination of cfTL to undetectable levels. For 14 patients, we observed initial molecular responses, followed by ctDNA recrudescence. A subset of patients (n = 10) displayed a clear pattern of molecular progression, with persistence of cfTL across all time points. Molecular responses captured the therapeutic effect and long-term clinical outcomes in a more accurate and rapid manner compared with radiographic imaging. Patients with sustained molecular responses had longer overall (log-rank P = 0.0006) and progression-free (log-rank P &lt; 0.0001) survival, with molecular responses detected on average 4 weeks earlier than imaging.

Conclusions:
ctDNA analyses provide a precise approach for the assessment of early on-therapy molecular responses and have important implications for the management of patients with SCLC, including the development of improved strategies for real-time tumor burden monitoring.
See related commentary by Pellini and Chaudhuri, p. 2176
Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma
Authors: Mender Ilgen , Siteni Silvia , Barron Summer , Flusche Ann Marie , Kubota Naoto , Yu Chunhua , Cornelius Crystal , Tedone Enzo , Maziveyi Mazvita , Grichuk Anthony , Venkateswaran Niranjan , Conacci-Sorrell Maralice , Hoshida Yujin , Kang Rui , Tang Daolin , Gryaznov Sergei , Shay Jerry W. 
Published: April 2023

Abstract
A select group of patients with hepatocellular carcinomas (HCC) benefit from surgical, radiologic, and systemic therapies that include a combination of anti-angiogenic and immune-checkpoint inhibitors. However, because HCC is generally asymptomatic in its early stages, this not only leads to late diagnosis, but also to therapy resistance. The nucleoside analogue 6-thio-dG (THIO) is a first-in-class telomerase-mediated telomere-targeting anticancer agent. In telomerase expressing cancer cells, THIO is converted into the corresponding 5′-triphosphate, which is efficiently incorporated into telomeres by telomerase, activating telomere damage responses and apoptotic pathways. Here, we show how THIO is effective in controlling tumor growth and, when combined with immune checkpoint inhibitors, is even more effective in a T-cell-dependent manner. We also show telomere stress induced by THIO increases both innate sensing and adaptive antitumor immunity in HCC. Importantly, the extracellular high-mobility group box 1 protein acts as a prototypical endogenous DAMP (Damage Associated Molecular Pattern) in eliciting adaptive immunity by THIO. These results provide a strong rationale for combining telomere-targeted therapy with immunotherapy.
Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma
Authors: Hoppe Michal Marek , Jaynes Patrick , Shuangyi Fan , Peng Yanfen , Sridhar Shruti , Hoang Phuong Mai , Liu Clementine Xin , De Mel Sanjay , Poon Limei , Chan Esther Hian Li , Lee Joanne , Ong Choon Kiat , Tang Tiffany , Lim Soon Thye , Nagarajan Chandramouli , Grigoropoulos Nicholas F. , Tan Soo-Yong , Hue Susan Swee-Shan , Chang Sheng-Tsung , Chuang Shih-Sung , Li Shaoying , Khoury Joseph D. , Choi Hyungwon , Harris Carl , Bottos Alessia , Gay Laura J. , Runge Hendrik F.P. , Moutsopoulos Ilias , Mohorianu Irina , Hodson Daniel J. , Farinha Pedro , Mottok Anja , Scott David W. , Pitt Jason J. , Chen Jinmiao , Kumar Gayatri , Kannan Kasthuri , Chng Wee Joo , Chee Yen Lin , Ng Siok-Bian , Tripodo Claudio , Jeyasekharan Anand D. 
Published: April 2023

Abstract

Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6− (M+2+6−) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6− percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and MYC/BCL2/BCL6-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6− unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance.

Significance:
Using single-cell–resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer.
This article is highlighted in the In This Issue feature, p. 1027
The Polyamine–Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma
Authors: Nakanishi Shima , Li Jiannong , Berglund Anders E. , Kim Youngchul , Zhang Yonghong , Zhang Ling , Yang Chunying , Song Jinming , Mirmira Raghavendra G. , Cleveland John L. 
Published: April 2023

Abstract

The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine–hypusine circuit, which posttranslationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and maintenance of MYC-driven lymphoma, where the loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. Mechanistically, integrating RNA sequencing, ribosome sequencing, and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including regulators of G1–S phase cell-cycle progression and DNA replication. This circuit thus controls MYC's proliferative response, and it is also activated across multiple malignancies. These findings suggest the hypusine circuit as a therapeutic target for several human tumor types.

Significance:
Elevated EIF5A and the polyamine–hypusine circuit are manifest in many malignancies, including MYC-driven tumors, and eIF5A hypusination is necessary for MYC proliferative signaling. Not­ably, this circuit controls an oncogenic translational program essential for the development and maintenance of MYC-driven lymphoma, supporting this axis as a target for cancer prevention and treatment.
See related commentary by Wilson and Klein, p. 248.
This article is highlighted in the In This Issue feature, p. 247
Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950
Authors: Okano Fumiyoshi , Saito Takanori , Minamida Yoshitaka , Kobayashi Shinichi , Ido Takayoshi , Miyauchi Yasushi , Wasai Ukei , Akazawa Daisuke , Kume Masahiko , Ishibashi Masaki , Jiang Ke , Aicher Alexandra , Heeschen Christopher , Yonehara Tetsu 
Published: April 2023

Specific targets for cancer treatment are highly desirable, but still remain to be discovered. While previous reports suggested that CAPRIN-1 localizes in the cytoplasm, here we now show that part of this molecule is strongly expressed on the cell membrane surface in most solid cancers, but not normal tissues. Notably, the membrane expression of CAPRIN-1 extended to the subset of highly tumorigenic cancer stem cells and epithelial–mesenchymal transition (EMT)–induced metastatic cancer cells. In addition, we revealed that cancer cells with particularly high CAPRIN-1 surface expression exhibited enhanced tumorigenicity. We generated a therapeutic humanized anti-CAPRIN-1 antibody (TRK-950), which strongly and specifically binds to various cancer cells and shows antitumor effects via engagement of immune cells. TRK-950 was further developed as a new cancer drug and a series of preclinical studies demonstrates its therapeutic potency in tumor-bearing mouse models and safety in a relevant cynomolgus monkey model. Together, our data demonstrate that CAPRIN-1 is a novel and universal target for cancer therapies. A phase I clinical study of TRK-950 has been completed (NCT02990481) and a phase Ib study (combination with approved drugs) is currently underway (NCT03872947) in the United States and France. In parallel, a phase I study in Japan is in progress as well (NCT05423262).

Significance:
Antibody-based cancer therapies have been demonstrated to be effective, but are only approved for a limited number of targets, because the majority of these markers is shared with healthy tissue, which may result in adverse effects. Here, we have successfully identified CAPRIN-1 as a novel truly cancer-specific target, universally expressed on membranes of various cancer cells including cancer stem cells. Clinical studies are underway for the anti-CAPRIN-1 therapeutic antibody TRK-950.
Integrative Metatranscriptomic Analysis Reveals Disease-specific Microbiome–host Interactions in Oral Squamous Cell Carcinoma
Authors: Jain Vinay , Baraniya Divyashri , El-Hadedy Doaa E. , Chen Tsute , Slifker Michael , Alakwaa Fadhl , Cai Kathy Q. , Chitrala Kumaraswamy N. , Fundakowski Christopher , Al-Hebshi Nezar N. 
Published: April 2023

Studies on the microbiome of oral squamous cell carcinoma (OSCC) have been limited to 16S rRNA gene sequencing. Here, laser microdissection coupled with brute-force, deep metatranscriptome sequencing was employed to simultaneously characterize the microbiome and host transcriptomes and predict their interaction in OSCC. The analysis involved 20 HPV16/18-negative OSCC tumor/adjacent normal tissue pairs (TT and ANT) along with deep tongue scrapings from 20 matched healthy controls (HC). Standard bioinformatic tools coupled with in-house algorithms were used to map, analyze, and integrate microbial and host data. Host transcriptome analysis identified enrichment of known cancer-related gene sets, not only in TT versus ANT and HC, but also in the ANT versus HC contrast, consistent with field cancerization. Microbial analysis identified a low abundance yet transcriptionally active, unique multi-kingdom microbiome in OSCC tissues predominated by bacteria and bacteriophages. HC showed a different taxonomic profile yet shared major microbial enzyme classes and pathways with TT/ANT, consistent with functional redundancy. Key taxa enriched in TT/ANT compared with HC were Cutibacterium acnes, Malassezia restricta, Human Herpes Virus 6B, and bacteriophage Yuavirus. Functionally, hyaluronate lyase was overexpressed by C. acnes in TT/ANT. Microbiome-host data integration revealed that OSCC-enriched taxa were associated with upregulation of proliferation-related pathways. In a preliminary in vitro validation experiment, infection of SCC25 oral cancer cells with C. acnes resulted in upregulation of MYC expression. The study provides a new insight into potential mechanisms by which the microbiome can contribute to oral carcinogenesis, which can be validated in future experimental studies.Significance:Studies have shown that a distinct microbiome is associated with OSCC, but how the microbiome functions within the tumor interacts with the host cells remains unclear. By simultaneously characterizing the microbial and host transcriptomes in OSCC and control tissues, the study provides novel insights into microbiome-host interactions in OSCC which can be validated in future mechanistic studies.
African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J. 
Published: April 2023

African American (AA) prostate cancer associates with vitamin D3 deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex. Likewise, in AA cells, Assay for Transposase-Accessible Chromatin using sequencing established greater 1α,25(OH)2D3-regulated chromatin accessibility, chromatin immunoprecipitation sequencing revealed significant enhancer-enriched VDR cistrome, and RNA sequencing identified the largest 1α,25(OH)2D3-dependent transcriptome. These VDR functions were significantly corrupted in the isogenic AA RC43T prostate cancer cells, and significantly distinct from EA cell models. We identified reduced expression of the chromatin remodeler, BAZ1A, in three AA prostate cancer cohorts as well as RC43T compared with RC43N. Restored BAZ1A expression significantly increased 1α,25(OH)2D3-regulated VDR-dependent gene expression in RC43T, but not HPr1AR or LNCaP cells. The clinical impact of VDR cistrome-transcriptome relationships were tested in three different clinical prostate cancer cohorts. Strikingly, only in AA patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH)2D3-dependent open chromatin (i) predicted progression from high-grade prostatic intraepithelial neoplasia to prostate cancer; (ii) responded to vitamin D3 supplementation in prostate cancer tumors; (iii) differentially responded to 25(OH)D3 serum levels. Finally, partial correlation analyses established that BAZ1A and components of the VDR complex identified by RIME significantly strengthened the correlation between VDR and target genes in AA prostate cancer only. Therefore, VDR transcriptional control is most potent in AA prostate cells and distorted through a BAZ1A-dependent control of VDR function.

Significance:
Our study identified that genomic ancestry drives the VDR complex composition, genomic distribution, and transcriptional function, and is disrupted by BAZ1A and illustrates a novel driver for AA prostate cancer.
p35 is a Crucial Player in NK-cell Cytotoxicity and TGFβ-mediated NK-cell Dysfunction
Authors: Wong Derek P. , Fritz Claire E. , Feinberg Daniel , Huang Alex Y. , Parameswaran Reshmi 
Published: April 2023

Natural killer (NK) cells are innate lymphocytes with cytotoxic activity. Understanding the factors regulating cytotoxicity is crucial for improving NK-cell adoptive therapies. Here, we studied a previously unknown role of p35 (CDK5R1), a coactivator of cyclin-dependent kinase 5 (CDK5) in NK-cell function. p35 expression was thought to be neuronal-specific and the majority of studies are still focused on neuronal cells. Here, we show that CDK5 and p35 are expressed in NK cells and are kinase-active. NK cells from p35 knockout mice were analyzed and showed significantly increased cytotoxicity against murine cancer cells, while they did not show any differences in cell numbers or maturation stages. We confirmed this using human NK cells transduced with p35 short hairpin RNA (shRNA), showing similar increase in cytotoxicity against human cancer cells. Overexpression of p35 in NK cells resulted in moderate decrease in cytotoxicity, while expressing a kinase-dead mutant of CDK5 displayed increased cytotoxicity. Together, these data suggest that p35 negatively regulates NK-cell cytotoxicity. Surprisingly, we found that TGFβ, a known negative regulator of NK-cell cytotoxicity, induces p35 expression in NK cells. NK cells cultured with TGFβ exhibit reduced cytotoxicity, while NK cells transduced with p35 shRNA or mutant CDK5 expression exhibited partial reversal of this inhibitory effect pointing to an interesting hypothesis that p35 plays an important role in TGFβ-mediated NK-cell exhaustion.

Significance:
This study reports a role for p35 in NK-cell cytotoxicity and this might help to improve NK-cell adoptive therapy.