tbuckley/cabot-search huggingface dataset:
NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024
Authors: Al B. Benson, Alan P. Venook, Mohamed Adam, George Chang, Yi-Jen Chen, Kristen K. Ciombor, Stacey A. Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, Paul Haste, J. Randolph Hecht, Sarah Hoffe, Steven Hunt, Hisham Hussan, Kimberly L. Johung, Nora Joseph, Natalie Kirilcuk, Smitha Krishnamurthi, Midhun Malla, Jennifer K. Maratt, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, Benjamin Shogan, John M. Skibber, Constantinos T. Sofocleous, Anna Tavakkoli, Christopher G. Willett, Christina Wu, Frankie Jones, Lisa Gurski
Journal: Journal of the National Comprehensive Cancer Network (2024)

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a “watch-and-wait” nonoperative management approach for clinical complete responders to neoadjuvant therapy.
Current and Emerging Biomarkers: Impact on Risk Stratification for Neuroblastoma
Authors: Meredith S. Irwin, Kelly C. Goldsmith
Journal: Journal of the National Comprehensive Cancer Network (2024)

Neuroblastoma has heterogenous clinical presentations that are reflected by several well-defined clinical factors and biomarkers. Combinations of these clinical and biologic prognostic factors have been used for decades to generate classifiers to stratify patients into risk groups (low, intermediate, and high), which in turn are used to inform and tailor treatment as reported in the new NCCN Clinical Practice Guidelines in Oncology for Neuroblastoma. Risk classification uses clinical features, such as age and tumor stage, along with the most significant prognostic tumor biomarkers, including histologic features (differentiation and mitosis-karyorrhexis index), MYCN amplification status, chromosomal copy number alterations (segmental or numerical), and ploidy (DNA content). Recent next-generation sequencing approaches have identified additional tumor-specific genetic factors that have potential roles as prognostic and predictive biomarkers. These emerging biomarkers include telomerase maintenance mechanisms, such as telomerase reverse transcription (TERT) expression and alternative lengthening of telomeres (ALT) status. Somatic alterations of genes, including mutations in the anaplastic lymphoma kinase gene ALK, detected in >10% of patients with newly diagnosed disease, have both prognostic and predictive roles in determining eligibility for targeted therapies (eg, ALK tyrosine kinase inhibitors). In addition to diagnostic tumor-derived biomarkers, significant effort is being directed toward identification of markers to predict response to chemotherapy and immunotherapies. With the increasing use of GD2-containing immunotherapy regimens, efforts are aimed at identifying host or tumor microenvironment immune correlatives that can serve as predictive biomarkers. Understanding the potential role of liquid biopsies as biomarkers during and following treatment, including sequential circulating tumor DNA or tumor-specific mRNA transcripts, is expected to enhance the ability to predict recurrences and also inform understanding of tumor evolution and therapy resistance. These and other emerging biomarkers will lead to refinement and optimization of future neuroblastoma risk classification systems.
A survey of the representativeness and usefulness of wastewater-based surveillance systems in 10 countries across Europe in 2023
Authors: Guido Benedetti, Lene Wulff Krogsgaard, Sabine Maritschnik, Hans Peter Stüger, Veronik Hutse, Raphael Janssens, Soile Blomqvist, Tarja Pitkänen, Anastasia Koutsolioutsou, Eszter Róka, Marta Vargha, Giuseppina La Rosa, Elisabetta Suffredini, Henry-Michel Cauchie, Leslie Ogorzaly, Rudolf FHJ van der Beek, Willemijn J Lodder, Elisabeth Henie Madslien, Jose Antonio Baz Lomba, Steen Ethelberg
Journal: Eurosurveillance (2024)

Wastewater-based surveillance (WBS) has become a widespread method to monitor transmission of SARS-CoV-2 and other human pathogens in Europe. We conducted a survey about WBS systems’ objectives, approaches, representativeness and usefulness in 10 invited European countries in 2023, i.e. Austria, Belgium, Denmark, Finland, Greece, Hungary, Italy, Luxembourg, the Netherlands and Norway. All countries completed the study questionnaire about their SARS-CoV-2 WBS systems, and shared information about WBS of other pathogens as deemed relevant. SARS-CoV-2 WBS systems primarily monitored national and subnational trends (population coverage: 25–99%), and a majority (8/10) also tracked variant distribution. Nine of 10 countries reported that their SARS-CoV-2 WBS systems were representative of their population and all countries remarked that the findings were valuable for public health decision-making. Results were shared with relevant public health authorities and published via dedicated websites and/or dashboards. WBS systems of other pathogens were mostly in the early stages, with some countries implementing pilots. Notable exceptions were the well-established poliovirus surveillance systems in Finland, Italy and the Netherlands. This study brings understanding the diverse landscape of WBS in Europe, offering insights for future developments and collaborations. Furthermore, it highlights the need for further integration of WBS into other European surveillance systems.
Weight gain leads to greater adverse metabolic responses in South Asian compared with white European men: the GlasVEGAS study
Authors: James McLaren, Xuan Gao, Nazim Ghouri, Dilys J. Freeman, Janice Richardson, Naveed Sattar, Jason M. R. Gill
Journal: Nature Metabolism (2024)

Abstract South Asians (SAs) develop type 2 diabetes at lower body mass index values than white Europeans (WEs). This basic human experimental study aimed to compare the metabolic consequences of weight gain in SA and WE men without overweight or obesity. Fourteen SAs and 21 WEs had assessments of body composition, metabolic responses to mixed-meal ingestion, cardiorespiratory fitness and physical activity, and a subcutaneous abdominal adipose tissue biopsy, before and after 4–6 weeks of overfeeding to induce 5–7% weight gain. Here we show that body mass index and whole-body adipose tissue volume increases similarly between ethnic groups, but SAs gain less lean tissue. SAs experience a substantially greater decrease in insulin sensitivity compared with WEs (38% versus 7% decrease, P = 0.009), have fewer small (37.1% versus 60.0%, P = 0.003) and more large (26.2% versus 9.1%, P = 0.005) adipocytes at baseline and have a smaller decrease in very small adipocytes with weight gain (−0.1% versus −1.9%, P &lt; 0.0001). Ethnic differences in adipocyte morphology are associated with SA’s greater adverse metabolic changes with weight gain. ClinicalTrials.gov registration: NCT02399423 .
Differences between males and females in infectious diseases notifications in the EU/EEA, 2012 to 2021
Authors: Julien Beauté, Francesco Innocenti
Journal: Eurosurveillance (2024)

Background There are differences between males and females for most diseases both for exposure and course of illness, including outcome. These differences can be related to biological sex or gender i.e. socio-cultural factors that may impact exposure and healthcare access. Aim We aimed to quantify differences between males and females in infectious disease notifications in Europe and identify countries with these differences significantly different from the European Union and European Economic Area (EU/EEA) average. Methods Notifiable infectious disease surveillance data are reported by EU/EEA countries to ECDC. We retrieved surveillance data for 2012−2021. Using a cut-off median of annual disability-adjusted life years above 1 per 100,000 population, we included 16 infectious diseases. We calculated median male proportion and interquartile range by disease, year, country and age group and used boxplots to identify outliers. Results For campylobacteriosis, acute hepatitis B, Legionnaires’ disease, malaria and HIV and AIDS, all countries had male proportion above 50%. Most countries had a male proportion below 50% for pertussis (25/28 countries), STEC infection (21/28 countries) and Chlamydia trachomatis infection (16/24 countries). Chlamydia trachomatis infection and listeriosis showed the greatest dispersion of male proportion across age groups. Most outliers were countries reporting few cases. Conclusion We observed important differences in male proportion across infectious disease notifications in EU/EEA countries. For some diseases with high male proportions in all countries, such as HIV and hepatitis B, behaviours play a role in disease transmission. Screening offered to specific populations may explain differences across countries for example for C. trachomatis infection.
A new silicon phthalocyanine dye induces pyroptosis in prostate cancer cells during photoimmunotherapy
Authors: Isis Wolf, Jonas Storz, Susanne Schultze-Seemann, Philipp R Esser, Stefan F Martin, Susan Lauw, Peer Fischer, Marie Peschers, Wolfgang Melchinger, Robert Zeiser, Oliver Gorka, Olaf Groß, Christian Gratzke, Reinhard Brückner, Philipp Wolf
Journal: Bioactive Materials (2024)

Photoimmunotherapy (PIT) combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers (PS) and is a promising new cancer therapy. We designed and synthesized, in a highly convergent manner, the silicon phthalocyanine dye WB692-CB2, which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines. In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen (PSMA). The resulting antibody dye conjugate revealed high affinity and specificity towards PSMA-expressing prostate cancer cells and induced cell death after irradiation with red light. Treated cells exhibited morphological characteristics associated with pyroptosis. Mechanistic studies revealed the generation of reactive oxygen species, triggering a cascade of intracellular events involving lipid peroxidation, caspase-1 activation, gasdermin D cleavage and membrane rupture followed by release of pro-inflammatory cellular contents. In first
NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors
Authors: Kensuke Nakagawara, Makoto Ando, Tanakorn Srirat, Setsuko Mise-Omata, Taeko Hayakawa, Minako Ito, Koichi Fukunaga, Akihiko Yoshimura
Journal: Journal for ImmunoTherapy of Cancer (2024)

Antitumor effect of chimeric antigen receptor (CAR)-T cells against solid tumors is limited due to various factors, such as low infiltration rate, poor expansion capacity, and exhaustion of T cells within the tumor. NR4A transcription factors have been shown to play important roles in T-cell exhaustion in mice. However, the precise contribution of each NR4a factor to human T-cell differentiation remains to be clarified.
Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology
Authors: Rochelle Bagatell, Julie R. Park, Sahaja Acharya, Jennifer Aldrink, Jenna Allison, Elizabeth Alva, Carola Arndt, Daniel Benedetti, Erin Brown, Steve Cho, Alanna Church, Andrew Davidoff, Ami Desai, Steven DuBois, Douglas Fair, Joaquim Farinhas, Douglas Harrison, Frederick Huang, Paul Iskander, Susan Kreissman, Margaret Macy, Brian Na, Farzana Pashankar, Praveen Pendyala, Navin Pinto, Stephanie Polites, Raja Rabah, Hiroyuki Shimada, Leonora Slatnick, Elizabeth Sokol, Clare Twist, Kieuhoa Vo, Tanya Watt, Suzanne Wolden, Peter Zage, Ryan Schonfeld, Lisa Hang
Journal: Journal of the National Comprehensive Cancer Network (2024)

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.
Effectiveness and Safety of Extended Treatment Apixaban Versus Low-Molecular-Weight Heparin in Cancer-Associated Venous Thromboembolism
Authors: Alexander T. Cohen, Amol D. Dhamane, Xuejun Liu, Risho Singh, Stella Han, Robert Stellhorn, Jane Wang, Xuemei Luo
Journal: Journal of the National Comprehensive Cancer Network (2024)

Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months.
Identification, risk factors, and clinical course of CNS relapse in DLBCL patients across 19 prospective phase 2 and 3 trials—a LYSA and GLA/ DSHNHL collaboration
Authors: Fabian Frontzek, Loïc Renaud, Ulrich Dührsen, Viola Poeschel, Sophie Bernard, Loïc Chartier, Nicolas Ketterer, Christian Récher, Olivier Fitoussi, Gerhard Held, Olivier Casasnovas, Corinne Haioun, Nicolas Mounier, Hervé Tilly, Franck Morschhauser, Steven Le Gouill, Imke E. Karsten, Gerben Duns, Christian Steidl, David W. Scott, Wolfram Klapper, Andreas Rosenwald, German Ott, Thierry Molina, Georg Lenz, Marita Ziepert, Bettina Altmann, Catherine Thieblemont, Norbert Schmitz
Journal: Leukemia (2024)
StaVia: spatially and temporally aware cartography with higher-order random walks for cell atlases
Authors: Shobana V. Stassen, Minato Kobashi, Edmund Y. Lam, Yuanhua Huang, Joshua W. K. Ho, Kevin K. Tsia
Journal: Genome biology (2024)

Abstract Single-cell atlases pose daunting computational challenges pertaining to the integration of spatial and temporal information and the visualization of trajectories across large atlases. We introduce StaVia, a computational framework that synergizes multi-faceted single-cell data with higher-order random walks that leverage the memory of cells’ past states, fused with a cartographic Atlas View that offers intuitive graph visualization. This spatially aware cartography captures relationships between cell populations based on their spatial location as well as their gene expression and developmental stage. We demonstrate this using zebrafish gastrulation data, underscoring its potential to dissect complex biological landscapes in both spatial and temporal contexts.
Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives
Authors: Chenliang Zhang, Tingting Huang, Liping Li
Journal: Journal of Hematology & Oncology (2024)

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation of dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and the loss of iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress and triggering cell death. Recently, cuproptosis has garnered significant interest in tumor research due to its potential as a crucial therapeutic strategy against cancer. In this review, we summarized the cellular and molecular mechanisms of cuproptosis and its relationship with other types of cell death. Additionally, we reviewed the current drugs or strategies available to induce cuproptosis in tumor cells, including Cu ionophores, small compounds, and nanomedicine. Furthermore, we targeted cell metabolism and specific regulatory genes in cancer therapy to enhance tumor sensitivity to cuproptosis. Finally, we discussed the feasibility of targeting cuproptosis to overcome tumor chemotherapy and immunotherapy resistance and suggested future research directions. This study suggested that targeting cuproptosis could open new avenues for developing tumor therapy.
EU-US data transfers: an enduring challenge for health research collaborations
Authors: Teodora Lalova-Spinks, Peggy Valcke, John P. A. Ioannidis, Isabelle Huys
Journal: npj Digital Medicine (2024)

EU-US data transfers for health research remain a particularly thorny issue in view of the stringent rules of the EU General Data Protection Regulation (GDPR) and the challenges related to US mass surveillance programs, particularly the manner in which US law enforcement and national security agencies can access personal data originating from the EU. Since the entry into force of the GDPR, evidence of impeded collaborations is increasing, particularly in the case of sharing data with US public institutions. The adoption of a new EU-US adequacy decision in July 2023 does not hold the promise for a long-lasting solution due to the risks of being challenged and invalidated – yet again – at the Court of Justice of the EU. As the research community is calling for answers, the new proposal for a European Health Data Space regulation may hold a key to solving some of the existing issues. In this paper, we critically discuss the current rules and outline a possible way forward for transfers between public bodies.
Comparisons of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy, in third-line or later relapsed/refractory large B-cell lymphoma
Authors: Allison Rosenthal, Javier Munoz, Monika Jun, Tongsheng Wang, Alex Mutebi, Anthony Wang, Shibing Yang, Kojo Osei-Bonsu, Brian Elliott, Fernando Rivas Navarro, Junhua Yu, Samantha Brodkin, Mariana Sacchi, Andrew Ip
Journal: Journal of Hematology & Oncology (2024)

Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.
scParser: sparse representation learning for scalable single-cell RNA sequencing data analysis
Authors: Kai Zhao, Hon-Cheong So, Zhixiang Lin
Journal: Genome biology (2024)

The rapid rise in the availability and scale of scRNA-seq data needs scalable methods for integrative analysis. Though many methods for data integration have been developed, few focus on understanding the heterogeneous effects of biological conditions across different cell populations in integrative analysis. Our proposed scalable approach, scParser, models the heterogeneous effects from biological conditions, which unveils the key mechanisms by which gene expression contributes to phenotypes. Notably, the extended scParser pinpoints biological processes in cell subpopulations that contribute to disease pathogenesis. scParser achieves favorable performance in cell clustering compared to state-of-the-art methods and has a broad and diverse applicability.
Benchmarking computational methods for single-cell chromatin data analysis
Authors: Siyuan Luo, Pierre-Luc Germain, Mark D. Robinson, Ferdinand von Meyenn
Journal: Genome biology (2024)

Abstract Background Single-cell chromatin accessibility assays, such as scATAC-seq, are increasingly employed in individual and joint multi-omic profiling of single cells. As the accumulation of scATAC-seq and multi-omics datasets continue, challenges in analyzing such sparse, noisy, and high-dimensional data become pressing. Specifically, one challenge relates to optimizing the processing of chromatin-level measurements and efficiently extracting information to discern cellular heterogeneity. This is of critical importance, since the identification of cell types is a fundamental step in current single-cell data analysis practices. Results We benchmark 8 feature engineering pipelines derived from 5 recent methods to assess their ability to discover and discriminate cell types. By using 10 metrics calculated at the cell embedding, shared nearest neighbor graph, or partition levels, we evaluate the performance of each method at different data processing stages. This comprehensive approach allows us to thoroughly understand the strengths and weaknesses of each method and the influence of parameter selection. Conclusions Our analysis provides guidelines for choosing analysis methods for different datasets. Overall, feature aggregation, SnapATAC, and SnapATAC2 outperform latent semantic indexing-based methods. For datasets with complex cell-type structures, SnapATAC and SnapATAC2 are preferred. With large datasets, SnapATAC2 and ArchR are most scalable.