tbuckley/cabot-search huggingface dataset:
A CT-based multitask deep learning model for predicting tumor stroma ratio and treatment outcomes in patients with colorectal cancer: a multicenter cohort study
Authors: Yanfen Cui, Ke Zhao, Xiaochun Meng, Yun Mao, Chu Han, Zhenwei Shi, Xiaotang Yang, Tong Tong, Lei Wu, Zaiyi Liu
Journal: International Journal of Surgery (2024)

Background: Tumor-stroma interactions, as indicated by tumor-stroma ratio (TSR), offer valuable prognostic stratification information. Current histological assessment of TSR is limited by tissue accessibility and spatial heterogeneity. We aimed to develop a multitask deep learning (MDL) model to noninvasively predict TSR and prognosis in colorectal cancer (CRC). Materials and Methods: In this retrospective study including 2268 patients with resected CRC recruited from four centers, we developed an MDL model using preoperative CT images for the simultaneous prediction of TSR and overall survival. Patients in the training cohort (n=956) and internal validation cohort (IVC, n=240) were randomly selected from center I. Patients in the external validation cohort1(EVC1, n=509), EVC2 (n=203), and EVC3 (n=360) were recruited from other three centers. Model performance was evaluated with respect to discrimination and calibration. Furthermore, we evaluated whether the model could predict the benefit from adjuvant chemotherapy. Results: The MDL model demonstrated strong TSR discrimination, yielding areas under the receiver operating curves (AUCs) of 0.855 (95%CI, 0.800-0.910), 0.838(95% CI, 0.802-0.874), and 0.857(95% CI, 0.804-0.909) in the three validation cohorts, respectively. The MDL model was also able to predict overall survival and disease-free survival across all cohorts. In multivariable Cox analysis, the MDL score (MDLS) remained an independent prognostic factor after adjusting for clinicopathological variables (all P &lt;0.05). For stage II and stage III disease, patients with a high MDLS benefited from adjuvant chemotherapy (hazard ratio [HR] 0.391 [95%CI, 0.230–0.666], P =0.0003; HR=0.467[95%CI, 0.331-0.659], P &lt;0.0001, respectively), whereas those with a low MDLS did not. Conclusion: The multitask DL model based on preoperative CT images effectively predicted TSR status and survival in CRC patients, offering valuable guidance for personalized treatment. Prospective studies are needed to confirm its potential to select patients who might benefit from chemotherapy.
Does patient size matter when comparing the operation time between single-incision and conventional laparoscopic sleeve gastrectomy?
Authors: Cheuk-Kwan Sun, I-Wen Chen, I-Ting Tsai, Kuo-Chuan Hung
Journal: International Journal of Surgery (2024)

aDepartment of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung City, Taiwan bSchool of Medicine, College of Medicine, I-Shou University, Kaohsiung city, Taiwan cDepartment of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan city, Taiwan dDepartment of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung city, Taiwan eDepartment of Anesthesiology, Chi Mei Medical Center, Tainan city, Taiwan Short title: Usefulness of single-incision laparoscopic sleeve gastrectomy Footnote: The affiliations for I-Wen Chen (affiliation 3) and Kuo-Chuan Hung (affiliation 5) represent different hospitals, despite both being under the Chi Mei Medical Center. These affiliations should not be combined or confused as they are distinct entities within different locations I-Wen Chen and Cheuk-Kwan Sun contributed equally as first authors to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Department of Anesthesiology, Chi Mei Medical Center, Tainan city, Taiwan, Chi Mei Medical Center, No.901, ChungHwa Road, YungKung Dist, Tainan 71004, Taiwan. Tel: +886-6-281-2811; fax: +886-6-283-3806. E-mail address: [email protected] (K-C. Hung). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Postgraduate Institute of India (<scp>PGI</scp>) textbook of laboratory and clinical hematology. By Koyamangalath Krishnan (Ed.), Mumbai, India: Bhalani Publishing House. 2024. pp. 3244. ISBN: 9789381496763
Authors: Rajiv K. Pruthi
Journal: American Journal of Hematology (2024)

Author declares no conflict of interest.
pyHiM: a new open-source, multi-platform software package for spatial genomics based on multiplexed DNA-FISH imaging
Authors: Xavier Devos, Jean-Bernard Fiche, Marion Bardou, Olivier Messina, Christophe Houbron, Julian Gurgo, Marie Schaeffer, Markus Götz, Thomas Walter, Florian Mueller, Marcelo Nollmann
Journal: Genome biology (2024)

Abstract Genome-wide ensemble sequencing methods improved our understanding of chromatin organization in eukaryotes but lack the ability to capture single-cell heterogeneity and spatial organization. To overcome these limitations, new imaging-based methods have emerged, giving rise to the field of spatial genomics. Here, we present pyHiM, a user-friendly python toolbox specifically designed for the analysis of multiplexed DNA-FISH data and the reconstruction of chromatin traces in individual cells. pyHiM employs a modular architecture, allowing independent execution of analysis steps and customization according to sample specificity and computing resources. pyHiM aims to facilitate the democratization and standardization of spatial genomics analysis.
Finding the Middle Ground for Intravenous Therapy
Authors: Vineet Chopra
Journal: JAMA Network Open (2024)

With shifts in care delivery from inpatient to outpatient settings, a growing need for reliable devices that enable intravenous (IV) therapies outside the hospital has emerged. 1 Peripherally inserted central catheters (PICCs) have longed served as the go-to device for this purpose.PICCs offer many advantages in this regard, eg, their insertion in the hospital or home setting is straightforward and convenient; they provide durable venous access for both infusion and phlebotomy; patients and families can be taught to care for them with relative ease; and home-based teams or skilled nursing facilities are well versed in managing these devices.
Atrial function after percutaneous occluder device and suture-mediated patent fossa ovalis closure
Authors: Carmela Tarsia, Carlo Gaspardone, Antonella De Santis, Emanuela D’Ascoli, Fabiana Piccioni, Gregory Angelo Sgueglia, Maria Iamele, Stefania Leonetti, Maria Benedetta Giannico, Achille Gaspardone
Journal:  (2024)

Abstract Aims Suture-mediated patent fossa ovalis (PFO) closure is a recent technique, achieving closure by means of a simple suture. The differences between traditional occluders and suture might have different impacts on atrial function. The aim of this study was to evaluate atrial function after PFO closure by direct suture and traditional occluders. Methods and results We prospectively studied 40 patients, 20 undergoing PFO closure by occluder and 20 by suture. Trans-thoracic echocardiography was carried out the day before and 1 year after the procedure. Left atrial (LA) and right atrial (RA) function was evaluated by using speckle-tracking analysis assessing the strain values of the reservoir (st-RES), conduit (st-CD), and contraction phase (st-CT). Compared with values baseline PFO closure, at 1-year follow-up, patients with occluder implantation had significantly worse indices of LA and RA reservoir (LA st-RES P &amp;lt; 0.001; RA st-RES P &amp;lt; 0.001), conduit (LA st-CD P &amp;lt; 0.001; RA st-CD P &amp;lt; 0.001), and contraction function (LA st-CT P &amp;lt; 0.05; RA st-CT P &amp;lt; 0.05). In patients with suture-mediated PFO closure, no significant differences were observed in the same indices of reservoir (LA st-RES P = 0.848; RA st-RES P = 0.183), conduit (LA st-CD P = 0.156; RA st-CD P = 0.419), and contraction function (LA st-CT P = 0.193; RA st-CT P = 0.375). Conclusion Suture-mediated PFO closure does not alter atrial function. Conversely, PFO closure by metallic occluders is associated with a deterioration of atrial function. This detrimental effect on atrial function could favour the development of atrial arrhythmias.
A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma
Authors: Christina L. Roland, Elise F. Nassif Haddad, Emily Z. Keung, Wei-Lien Wang, Alexander J. Lazar, Heather Lin, Manoj Chelvanambi, Edwin R. Parra, Khalida Wani, B. Ashleigh Guadagnolo, Andrew J. Bishop, Elizabeth M. Burton, Kelly K. Hunt, Keila E. Torres, Barry W. Feig, Christopher P. Scally, Valerae O. Lewis, Justin E. Bird, Ravin Ratan, Dejka Araujo, M. Alexandra Zarzour, Shreyaskumar Patel, Robert Benjamin, Anthony P. Conley, J. Andrew Livingston, Vinod Ravi, Hussein A. Tawbi, Patrick P. Lin, Bryan S. Moon, Robert L. Satcher, Bilal Mujtaba, Russell G. Witt, Raymond S. Traweek, Brandon Cope, Rossana Lazcano, Chia-Chin Wu, Xiao Zhou, Mohammad M. Mohammad, Randy A. Chu, Jianhua Zhang, Ashish Damania, Pranoti Sahasrabhojane, Taylor Tate, Kate Callahan, Sa Nguyen, Davis Ingram, Rohini Morey, Shadarra Crosby, Grace Mathew, Sheila Duncan, Cibelle F. Lima, Jean-Yves Blay, Wolf Herman Fridman, Kenna Shaw, Ignacio Wistuba, Andrew Futreal, Nadim Ajami, Jennifer A. Wargo, Neeta Somaiah
Journal: Nature Cancer (2024)
Interplay of a well‐known medication and newly discovered transporters driving bacteria‐induced inflammation in psoriasis
Authors: Greta Lücke
Journal: Allergy (2024)

SLC46A2 is crucial for the transportation of DAP-muropeptides into the cytosol, leading to NOD1 activation. Subsequent neutrophil recruitment through the release of IL-1α proves to be critical for the progression of psoriatic inflammation. The commonly prescribed anti-inflammatory drug methotrexate inhibits Slc46a2-mediated DAP-muropeptide transport in the mouse model, suggesting a therapeutic mechanism for suppressing psoriatic inflammation. C. accolens; Corynebacterium accolens; DAP, diaminopimelic acid; IMQ, imiquimod; MTX, methotrexate; Nod, nucleotide-binding and oligomerization domain; ns, not stimulated; SLC46, solute carrier family 46 The author declares no conflict of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
The dopamine transporter antagonist vanoxerine inhibits G9a and suppresses cancer stem cell functions in colon tumors
Authors: Christopher J. Bergin, Aïcha Zouggar, Amanda Mendes da Silva, Tanguy Fenouil, Joshua R. Haebe, Angelique N. Masibag, Gautam Agrawal, Muhammad S. Shah, Tamara Sandouka, Mario Tiberi, Rebecca C. Auer, Michele Ardolino, Yannick D. Benoit
Journal: Nature Cancer (2024)
Selenium reduction of ubiquinone via SQOR suppresses ferroptosis
Authors: Namgyu Lee, Sung Jin Park, Mike Lange, Tenzin Tseyang, Mihir B. Doshi, Tae Yong Kim, Yoseb Song, Dong In Kim, Paul L. Greer, James A. Olzmann, Jessica B. Spinelli, Dohoon Kim
Journal: Nature Metabolism (2024)
Distinct ontogenetic lineages dictate cDC2 heterogeneity
Authors: Carlos M. Minutti, Cécile Piot, Mariana Pereira da Costa, Probir Chakravarty, Neil Rogers, Hector Huerga Encabo, Ana Cardoso, Jane Loong, Gilles Bessou, Cyrille Mionnet, Jean Langhorne, Dominique Bonnet, Marc Dalod, Elena Tomasello, Caetano Reis e Sousa
Journal: Nature Immunology (2024)

Abstract Conventional dendritic cells (cDCs) include functionally and phenotypically diverse populations, such as cDC1s and cDC2s. The latter population has been variously subdivided into Notch-dependent cDC2s, KLF4-dependent cDC2s, T-bet + cDC2As and T-bet − cDC2Bs, but it is unclear how all these subtypes are interrelated and to what degree they represent cell states or cell subsets. All cDCs are derived from bone marrow progenitors called pre-cDCs, which circulate through the blood to colonize peripheral tissues. Here, we identified distinct mouse pre-cDC2 subsets biased to give rise to cDC2As or cDC2Bs. We showed that a Siglec-H + pre-cDC2A population in the bone marrow preferentially gave rise to Siglec-H − CD8α + pre-cDC2As in tissues, which differentiated into T-bet + cDC2As. In contrast, a Siglec-H − fraction of pre-cDCs in the bone marrow and periphery mostly generated T-bet − cDC2Bs, a lineage marked by the expression of LysM. Our results showed that cDC2A versus cDC2B fate specification starts in the bone marrow and suggest that cDC2 subsets are ontogenetically determined lineages, rather than cell states imposed by the peripheral tissue environment.
Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial
Authors: Benjamin Besse, Elvire Pons-Tostivint, Keunchil Park, Sylvia Hartl, Patrick M. Forde, Maximilian J. Hochmair, Mark M. Awad, Michael Thomas, Glenwood Goss, Paul Wheatley-Price, Frances A. Shepherd, Marie Florescu, Parneet Cheema, Quincy S. C. Chu, Sang-We Kim, Daniel Morgensztern, Melissa L. Johnson, Sophie Cousin, Dong-Wan Kim, Mor T. Moskovitz, David Vicente, Boaz Aronson, Rosalind Hobson, Helen J. Ambrose, Sajan Khosla, Avinash Reddy, Deanna L. Russell, Mohamed Reda Keddar, James P. Conway, J. Carl Barrett, Emma Dean, Rakesh Kumar, Marlene Dressman, Philip J. Jewsbury, Sonia Iyer, Simon T. Barry, Jan Cosaert, John V. Heymach
Journal: Nature Medicine (2024)

Abstract For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11 /LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)–ceralasertib (ATR kinase inhibitor), durvalumab–olaparib (PARP inhibitor), durvalumab–danvatirsen (STAT3 antisense oligonucleotide) or durvalumab–oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab–ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6–7.4) versus 2.7 (1.8–2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1–20.3) versus 9.4 (7.5–10.6) months. Benefit with durvalumab–ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM -altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab–ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab–ceralasertib is under further investigation in immunotherapy-refractory NSCLC. ClinicalTrials.gov identifier: NCT03334617
Large-scale gene expression alterations introduced by structural variation drive morphotype diversification in Brassica oleracea
Authors: Xing Li, Yong Wang, Chengcheng Cai, Jialei Ji, Fengqing Han, Lei Zhang, Shumin Chen, Lingkui Zhang, Yinqing Yang, Qi Tang, Johan Bucher, Xuelin Wang, Limei Yang, Mu Zhuang, Kang Zhang, Honghao Lv, Guusje Bonnema, Yangyong Zhang, Feng Cheng
Journal: Nature Genetics (2024)

Abstract Brassica oleracea , globally cultivated for its vegetable crops, consists of very diverse morphotypes, characterized by specialized enlarged organs as harvested products. This makes B. oleracea an ideal model for studying rapid evolution and domestication. We constructed a B. oleracea pan-genome from 27 high-quality genomes representing all morphotypes and their wild relatives. We identified structural variations (SVs) among these genomes and characterized these in 704 B. oleracea accessions using graph-based genome tools. We show that SVs exert bidirectional effects on the expression of numerous genes, either suppressing through DNA methylation or promoting probably by harboring transcription factor-binding elements. The following examples illustrate the role of SVs modulating gene expression: SVs promoting BoPNY and suppressing BoCKX3 in cauliflower/broccoli, suppressing BoKAN1 and BoACS4 in cabbage and promoting BoMYBtf in ornamental kale. These results provide solid evidence for the role of SVs as dosage regulators of gene expression, driving B. oleracea domestication and diversification.
Response to correspondence: Prediction of adult asthma risk in early childhood using novel adult asthma predictive risk scores
Authors: Abdal J. Farhan, Dilini M. Kothalawala, Ramesh J. Kurukulaaratchy, Raquel Granell, Angela Simpson, Clare Murray, Adnan Custovic, Graham Roberts, Hongmei Zhang, S. Hasan Arshad
Journal: Allergy (2024)

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Multicancer screening test based on the detection of circulating non haematological proliferating atypical cells
Authors: Natalia Malara, Maria Laura Coluccio, Fabiana Grillo, Teresa Ferrazzo, Nastassia C. Garo, Giuseppe Donato, Annamaria Lavecchia, Franco Fulciniti, Anna Sapino, Eliano Cascardi, Antonella Pellegrini, Prassede Foxi, Cesare Furlanello, Giovanni Negri, Guido Fadda, Arrigo Capitanio, Salvatore Pullano, Virginia M. Garo, Francesca Ferrazzo, Alarice Lowe, Angela Torsello, Patrizio Candeloro, Francesco Gentile
Journal: Molecular Cancer (2024)

Abstract Background the problem in early diagnosis of sporadic cancer is understanding the individual’s risk to develop disease. In response to this need, global scientific research is focusing on developing predictive models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.e. atypical epithelial hyperplasia, is still in a subclinical stage of proliferative dysregulation. Methods a well-established procedure to identify proliferating circulating tumor cells was deployed to measure the cell proliferation of circulating non-haematological cells which may suggest tumor pathology. Moreover, the data collected were processed by a supervised machine learning model to make the prediction. Results the developed test combining circulating non-haematological cell proliferation data and artificial intelligence shows 98.8% of accuracy, 100% sensitivity, and 95% specificity. Conclusion this proof of concept study demonstrates that integration of innovative non invasive methods and predictive-models can be decisive in assessing the health status of an individual, and achieve cutting-edge results in cancer prevention and management.
Real‐world experience of pegcetacoplan in paroxysmal nocturnal hemoglobinuria
Authors: Morag Griffin, Richard Kelly, Isabelle Brindel, Lynda Maafa, Roochi Trikha, Petra Muus, Talha Munir, Abraham Mullasseril Varghese, Lindsay Mitchell, Sateesh Nagumantry, Shreyans Gandhi, Alex Pike, Austin G. Kulasekararaj, Regis Peffault de Latour
Journal: American Journal of Hematology (2024)

Pegcetacoplan significantly improves outcomes for patients with paroxysmal nocturnal hemoglobinuria (PNH) experiencing extravascular hemolysis (EVH) on eculizumab, leading to approval in 2021/2022 (USA/Europe). We report the first collaborative real-world evidence on pegcetacoplan use in UK and France. A total of 48 patients were either currently receiving or previously received pegcetacoplan (2019-2023). A total of 12 patients had participated in the PEGASUS clinical trial, continuing treatment after trial completion. Five patients were on combination treatment of C5 inhibition and pegcetacoplan. Mean pegcetacoplan duration was 20.2 months. Indication for pegcetacoplan was EVH on C5 inhibitors (Eculizumab, n = 29, Ravulizumab n = 16, others n = 3) with 35/48 patients requiring blood transfusion within the previous 12 months. Mean hemoglobin and reticulocyte count at pegcetacoplan commencement and after 3 months: 91 g/L and 205 × 10
Using Drosophila to uncover the role of organismal physiology and the tumor microenvironment in cancer
Authors: Chaitali Khan, Nasser M. Rusan
Journal: Trends in cancer (2024)

Cancer metastasis causes over 90% of cancer patient fatalities. Poor prognosis is determined by tumor type, the tumor microenvironment (TME), organ-specific biology, and animal physiology. While model organisms do not fully mimic the complexity of humans, many processes can be studied efficiently owing to the ease of genetic, developmental, and cell biology studies. For decades, Drosophila has been instrumental in identifying basic mechanisms controlling tumor growth and metastasis. The ability to generate clonal populations of distinct genotypes in otherwise wild-type animals makes Drosophila a powerful system to study tumor–host interactions at the local and global scales. This review discusses advancements in tumor biology, highlighting the strength of Drosophila for modeling TMEs and systemic responses in driving tumor progression and metastasis.
Targeting solid tumor antigens with chimeric receptors: cancer biology meets synthetic immunology
Authors: Gabriele J. Kembuan, Joanna Y. Kim, Marcela V. Maus, Max Jan
Journal: Trends in cancer (2024)

Chimeric antigen receptor (CAR) T cell therapy is a medical breakthrough in the treatment of B cell malignancies. There is intensive focus on developing solid tumor-targeted CAR-T cell therapies. Although clinically approved CAR-T cell therapies target B cell lineage antigens, solid tumor targets include neoantigens and tumor-associated antigens (TAAs) with diverse roles in tumor biology. Multiple early-stage clinical trials now report encouraging signs of efficacy for CAR-T cell therapies that target solid tumors. We review the landscape of solid tumor target antigens from the perspective of cancer biology and gene regulation, together with emerging clinical data for CAR-T cells targeting these antigens. We then discuss emerging synthetic biology strategies and their application in the clinical development of novel cellular immunotherapies.