tbuckley/cabot-search huggingface dataset:
Multi-modal cell-free DNA genomic and fragmentomic patterns enhance cancer survival and recurrence analysis
Authors: Norbert Moldovan, Ymke van der Pol, Tom van den Ende, Dries Boers, Sandra Verkuijlen, Aafke Creemers, Jip Ramaker, Trang Vu, Sanne Bootsma, Kristiaan J. Lenos, Louis Vermeulen, Marieke F. Fransen, Michiel Pegtel, Idris Bahce, Hanneke van Laarhoven, Florent Mouliere
Journal: Cell Reports Medicine (2023)

The structure of cell-free DNA (cfDNA) is altered in the blood of patients with cancer. From whole-genome sequencing, we retrieve the cfDNA fragment-end composition using a new software (FrEIA [fragment end integrated analysis]), as well as the cfDNA size and tumor fraction in three independent cohorts (n = 925 cancer from >10 types and 321 control samples). At 95% specificity, we detect 72% cancer samples using at least one cfDNA measure, including 64% early-stage cancer (n = 220). cfDNA detection correlates with a shorter overall (p = 0.0086) and recurrence-free (p = 0.017) survival in patients with resectable esophageal adenocarcinoma. Integrating cfDNA measures with machine learning in an independent test set (n = 396 cancer, 90 controls) achieve a detection accuracy of 82% and area under the receiver operating characteristic curve of 0.96. In conclusion, harnessing the biological features of cfDNA can improve, at no extra cost, the diagnostic performance of liquid biopsies.
ATR‐dependent ubiquitin‐specific protease 20 phosphorylation confers oxaliplatin and ferroptosis resistance
Authors: Jianing Tang, Guo Long, Desheng Xiao, Shuang Liu, Liang Xiao, Ledu Zhou, Yongguang Tao
Journal: MedComm (2023)

Oxaliplatin (OXA) resistance is a major clinic challenge in hepatocellular carcinoma (HCC). Ferroptosis is a kind of iron-dependent cell death. Triggering ferroptosis is considered to restore sensitivity to chemotherapy. In the present study, we found that USP20 was overexpressed in OXA-resistant HCC cells. High expression of USP20 in HCC was associated with poor prognosis. USP20 contributes OXA resistance and suppress ferroptosis in HCC. Pharmacological inhibition or knockdown of USP20 triggered ferroptosis and increased the sensitivity of HCC cells to OXA both in vitro and in vivo. Coimmunoprecipitation results revealed that the UCH domain of USP20 interacted with the N terminal of SLC7A11. USP20 stabilized SLC7A11 via removing K48-linked polyubiquitination of SLC7A11 protein at K30 and K37. Most importantly, DNA damage-induced ATR activation was required for Ser132 and Ser368 phosphorylation of USP20. USP20 phosphorylation at Ser132 and Ser368 enhanced its stability and thus conferred OXA and ferroptosis resistance of HCC cells. Our study reveals a previously undiscovered association between OXA and ferroptosis and provides new insight into mechanisms regarding how DNA damage therapies always lead to therapeutic resistance. Therefore, targeting USP20 may mitigate the development of drug resistance and promote ferroptosis of HCC in patients receiving chemotherapy.
PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma
Authors: Ghassan K Abou-Alfa, Peter R Galle, Yee Chao, Joseph Erinjeri, Jeong Heo, Mitesh J Borad, Angelo Luca, James Burke, Adina Pelusio, Delphine Agathon, Monika Lusky, Caroline Breitbach, Shukui Qin, Edward Gane
Journal: Liver Cancer (2023)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment. The primary endpoint is overall survival (OS). Key secondary endpoints included time to progression (TTP), progression-free survival, overall response rate (ORR), and disease control rate (DCR). Safety was assessed in all patients who received ≥1 dose of study treatment. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The study was conducted at 142 sites in 16 countries. From December 30, 2015, to the interim analysis on August 2, 2019, 459 patients were randomly assigned (pexa-vec plus sorafenib: 234, sorafenib: 225). At the interim analysis, the median OS was 12.7 months (95% CI: 9.89, 14.95) in the pexa-vec plus sorafenib arm and 14.0 months (95% CI: 11.01, 18.00) in the sorafenib arm. This led to the early termination of the study. The median TTP was 2.0 months (95% CI: 1.77, 2.96) and 4.2 months (95% CI: 2.92, 4.63); ORR was 19.2% (45 patients) and 20.9% (47 patients); and DCR was 50.0% (117 patients) and 57.3% (129 patients) in the pexa-vec plus sorafenib and sorafenib arms, respectively. Serious adverse events were reported in 117 (53.7%) patients in the pexa-vec plus sorafenib and 77 (35.5%) patients in the sorafenib arm. Liver failure was the most frequently reported in both groups. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Sequential pexa-vec plus sorafenib treatment did not demonstrate increased clinical benefit in advanced HCC and fared worse compared to sorafenib alone. The advent of the added value of checkpoint inhibitors should direct any further development of oncolytic virus therapy strategies.
Resected lymph nodes and survival of patients with esophageal squamous cell carcinoma in pT2 and pT3
Authors: Kexun Li, Xuefeng Leng, Lin Peng
Journal: International Journal of Surgery (2023)

aDivision of Thoracic Surgery, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China bDepartment of Thoracic Surgery I, Key Laboratory of Lung Cancer of Yunnan Province, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China Running title: Resected lymph nodes in esophageal carcinoma Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Division of Thoracic Surgery, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), 55 Section 4, South Renmin Road, Chengdu, Chengdu 610041, China, Tel: +8618908178797, Fax: 86-028-85420156. E-mail address: [email protected] (L. Peng). 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/
How long can pulmonary resection surgery be performed after SARS-CoV-2 infection? a multicenter retrospective study
Authors: Jiangnan Duan, Ying Zhou, Bengang Hui, Yabo Zhao, Rongxin Shang, Bowei Qiao, Yinxi Zhou, Weibo Yang, Kai Cui, Xi Zhang, Xiaolong Yan, Tao Jiang, Jie Lei
Journal: International Journal of Surgery (2023)

Background: No studies to date have focused on the timing of pulmonary resection in patients with previous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. In the present study, the authors analyzed the surgical outcomes and evaluated the optimal time point of pulmonary resection surgery following SARS-CoV-2 infection. Materials and methods: In this multicenter retrospective cohort study, patients were divided into different groups according to the time interval between SARS-CoV-2 diagnosis and pulmonary resection. The primary outcome measure was postoperative complications within 30 days after surgery, which was investigated to determine the optimal time point of pulmonary resection. Logistic regression models were used to calculate the risk factors for postoperative complications. Results: In total, 400 patients were enrolled, and the postoperative pathologic examination of 322 (80.5%) patients showed lung cancer. As the interval between SARS-CoV-2 infection and pulmonary resection increased, the incidence of complications gradually decreased in each group. The incidence of grade ≥II complications was higher in the ≤2-week and 2-week to 4-week groups than in the 4-week to 6-week, 6-week to 8-week and &gt;8-week groups [3 (21.4%), 17 (20.2%), 10 (10.6%), 13 (7.9%), and 3 (6.5%), respectively] ( P &lt;0.05). Multiclassification regression analysis showed that the risk of grade ≥II complications in the ≤2-week and 2-week to 4-week groups was significantly higher than that in the &gt;8-week group [odds ratio (95% CI), 3.937 (1.072–14.459), P =0.039 and 3.069 (1.232–6.863), P =0.015]. The logistic regression analysis suggested that underlying disease, persistent SARS-CoV-2 symptoms, and surgical timing (≤4 weeks) were independent risk factors for complications of pulmonary resection after SARS-CoV-2 infection. Conclusion: Pulmonary resection should be delayed for at least 4 weeks following SARS-CoV-2 infection to reduce the risk of postoperative complications.
Infectious disease among adults with allergic contact dermatitis: a propensity score-matched case–control study
Authors: Parsa Abdi, Zaim Haq, Michael J Diaz, Howard I Maibach
Journal: British Journal of Dermatology (2023)

Although recent studies have hinted at associations between allergic contact dermatitis (ACD) and infectious diseases, extensive cohort analyses on the direct correlations between ACD and increased susceptibility to these infections remain limited. After analysing the ‘All of Us’ database, which includes a diverse cohort of 287 011 participants, the study identified 4854 patients with ACD. Comparisons with matched controls revealed a significant association between ACD and various infectious cutaneous comorbidities. Specifically, individuals with ACD showed a heightened risk of conditions like impetigo, scabies, cutaneous herpes simplex virus, cutaneous candidiasis, cutaneous abscess and verruca vulgaris.
Human breastmilk-derived <i>Bifidobacterium longum</i> subsp. <i>infantis</i> CCFM1269 regulates bone formation by the GH/IGF axis through PI3K/AKT pathway
Authors: Mengfan Ding, Bowen Li, Haiqin Chen, Dong Liang, R. Paul Ross, Catherine Stanton, Jianxin Zhao, Wei Chen, Bo Yang
Journal: Gut Microbes (2023)

Bifidobacterium longum subsp. infantis is a prevalent member of the gut microbiota of breastfed infants. In this study, the effects of human breastmilk-derived B.longum subsp. infantis CCFM1269 on bone formation in developing BALB/c mice were investigated. Newborn female and male mice were assigned to control group (administered saline), CCFM1269 group (administered B. longum subsp. infantis CCFM1269, 1 × 109 CFU/mouse/day) and I5TI group (administered B. longum subsp. infantis I5TI, 1 × 109 CFU/mouse/day) from 1-week-old to 3-, 4- and 5-week old. B. longum subsp. infantis I5TI served as a negative control in this study. The results demonstrated that B. longum subsp. infantis CCFM1269 promoted bone formation in growing mice by modulating the composition of the gut microbiota and metabolites. The expression of genes and proteins in the PI3K/AKT pathway was stimulated by B. longum subsp. infantis CCFM1269 through the GH/IGF-1 axis in growing mice. This finding suggests B. longum subsp. infantis CCFM1269 may be useful for modulating bone metabolism during growth.
Assessing and managing mental health of people with vitiligo: UK-wide consultation exercise
Authors: Richard Barlow, Alia Ahmed, Jodie Fellows, Jon Goulding, Kelly Handley, Alex Schneider, Andrew Thompson, Marie Valente, Cerith Waters, Viktoria Eleftheriadou
Journal: British Journal of Dermatology (2023)

Significant variation exists in the assessment and management of people with vitiligo and psychological distress. This consultation exercise suggests an unmet need for an online, centralized intervention for people with vitiligo and moderate-to-severe psychological distress. Further actions should be taken to raise awareness of sources of support to clinicians around pathways available to mental health services.
A Novel Air Trapping Segment Score Identifies Opposing Effects of Obesity and Eosinophilia on Air Trapping in Asthma
Authors: Clarus Leung, Monica Tang, Brendan K Huang, Sean B Fain, Eric A. Hoffman, Jiwoong Choi, Eleanor M. Dunican, David T Mauger, Loren C Denlinger, Nizar N Jarjour, Elliot Israel, Bruce D. Levy, Sally E. Wenzel, Kaharu Sumino, Annette T Hastie, Joshua Schirm, Charles E. McCulloch, Michael C. Peters, Prescott G. Woodruff, Ronald L. Sorkness, Mario Castro, John V Fahy
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole-lung level but are not informative for AT in specific bronchopulmonary segments.
Nir‐Ii Emissive Superoxide Radical Photogenerator for Photothermal/photodynamic Therapy Against Hypoxic Tumor
Authors: Huichun Xiao, Yuran Wang, Jian Chen, Simin Xi, Zeyu Duan, Qiyu Zhan, Ye Tian, Lei Wang, Jinqing Qu, Ruiyuan Liu
Journal: Advanced Healthcare Materials (2023)

Abstract Due to the “Achilles' heels” of hypoxia, complicated location in solid tumor, small molecular photosensitizers with second near‐infrared window (NIR‐II) fluorescence, type‐I photodynamic therapy (PDT), and photothermal therapy (PTT) have attracted great attention. However, these photosensitizers are still few but yet challenging. Herein, an “all in one” NIR‐II acceptor–donor–acceptor fused‐ring photosensitizer, Y6‐Th, is presented for the in‐depth diagnosis and efficient treatment of cancer. Benefiting from the strong intramolecular charge transfer, promoted highly efficient intersystem crossing, largely p‐conjugated fused‐ring structure, and reduced planarity, the fabricated nanoparticles (Y6‐Th nanoparticles) can emit NIR‐II fluorescence with the peak located at 1020 nm, exclusively generate O2•− for type‐I PDT, and display excellent PTT performance under an 808 nm laser stimulation. These characteristics make Y6‐Th a distinguished NIR‐wavelength‐triggered phototheranostic agent, which can effectively therapy the hypoxic tumor using NIR‐II‐fluorescence‐guided type‐I PDT/PTT. This work provides a valuable guideline for fabricating high‐performing NIR‐II emissive superoxide radical photogenerators.
Nomogram for soiling prediction in post-surgery hirschsprung children: a retrospective study
Authors: Pei Wang, Erhu Fang, Xiang Zhao, Jiexiong Feng
Journal: International Journal of Surgery (2023)

Purpose: The aim of this study was to develop a nomogram for predicting the probability of postoperative soiling in patients aged greater than 1 year operated for Hirschsprung disease (HSCR). Materials and methods: The authors retrospectively analyzed HSCR patients with surgical therapy over 1 year of age from January 2000 and December 2019 at our department. Eligible patients were randomly categorized into the training and validation set at a ratio of 7:3. By integrating the least absolute shrinkage and selection operator [LASSO] and multivariable logistic regression analysis, crucial variables were determined for establishment of the nomogram. And, the performance of nomogram was evaluated by C-index, area under the receiver operating characteristic curve, calibration curves, and decision curve analysis. Meanwhile, a validation set was used to further assess the model. Results: This study enrolled 601 cases, and 97 patients suffered from soiling. Three risk factors, including surgical history, length of removed bowel, and surgical procedures were identified as predictive factors for soiling occurrence. The C-index was 0.871 (95% CI: 0.821–0.921) in the training set and 0.878 (95% CI: 0.811–0.945) in the validation set, respectively. And, the AUC was found to be 0.896 (95% CI: 0.855−0.929) in the training set and 0.866 (95% CI: 0.767−0.920) in the validation set. Additionally, the calibration curves displayed a favorable agreement between the nomogram model and actual observations. The decision curve analysis revealed that employing the nomogram to predict the risk of soiling occurrence would be advantageous if the threshold was between 1 and 73% in the training set and 3–69% in the validation set. Conclusion: This study represents the first efforts to develop and validate a model capable of predicting the postoperative risk of soiling in patients aged greater than 1 year operated for HSCR. This model may assist clinicians in determining the individual risk of soiling subsequent to HSCR surgery, aiding in personalized patient care and management.
Seladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis
Authors: Andreas E. Kremer, Marlyn J. Mayo, Gideon M. Hirschfield, Cynthia Levy, Christopher L. Bowlus, David E. Jones, Jeff D. Johnson, Charles A. McWherter, Yun-Jung Choi
Journal: Hepatology (2023)

Pruritus is a debilitating symptom for many people living with primary biliary cholangitis (PBC). In studies with seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, patients with PBC experienced significant improvement in pruritus and reduction of serum bile acids. Interleukin-31 (IL-31) is a cytokine known to mediate pruritus, and blocking IL-31 signaling provides relief in pruritic skin diseases. This study examined the connection between seladelpar's antipruritic effects and IL-31 and bile acid levels in patients with PBC.
An invited commentary on “preoperative ca19.9 level predicts lymph node metastasis in resectable adenocarcinoma of the head of the pancreas: a further plea for biological resectability criteria”
Authors: Roberto Valente, Chiara Maria Scandavini, Marco Del Chiaro
Journal: International Journal of Surgery (2023)

Valente, Roberto; Scandavini, Chiara Maria MD; Del Chiaro, Marco MD, PhD Author Information
A Large-Scale Meta-Analysis Reveals Positive Feedback between Macrophages and T Cells That Sensitizes Tumors to Immunotherapy
Authors: Jing Yang, Qi Liu, Yu Shyr
Journal: Cancer Research (2023)

Although considerable efforts have been dedicated to identifying predictive signatures for immune checkpoint inhibitor (ICI) treatment response, current biomarkers suffer from poor generalizability and reproducibility across different studies and cancer types. The integration of large-scale multiomics studies holds great promise for discovering robust biomarkers and shedding light on the mechanisms of immune resistance. In this study, we conducted the most extensive meta-analysis involving 3,037 ICI-treated patients with genetic and/or transcriptomics profiles across 14 types of solid tumor. The comprehensive analysis uncovered both known and novel reliable signatures associated with ICI treatment outcomes. The signatures included tumor mutational burden (TMB), IFNG and PDCD1 expression, and notably, interactions between macrophages and T cells driving their activation and recruitment. Independent data from single-cell RNA sequencing and dynamic transcriptomic profiles during the ICI treatment provided further evidence that enhanced cross-talk between macrophages and T cells contributes to ICI response. A multivariable model based on eight nonredundant signatures significantly outperformed existing models in five independent validation datasets representing various cancer types. Collectively, this study discovered biomarkers predicting ICI response that highlight the contribution of immune cell networks to immunotherapy efficacy and could help guide patient treatment.
Health-related quality of life trajectories up to 15 years after curative treatment for esophageal cancer: a prospective cohort study
Authors: Zhao Cheng, Asif Johar, Jesper Lagergren, Anna Schandl, Pernilla Lagergren
Journal: International Journal of Surgery (2023)

Background: The differentiation of specific, long-term health-related quality of life (HRQL) trajectories among esophageal cancer survivors remains unclear. The authors aimed to identify potentially distinctly different HRQL-trajectories and uncover the underlying factors of such trajectories in patients having undergone surgery (esophagectomy) for esophageal cancer. Materials and methods: This nationwide, prospective, and longitudinal cohort study included 420 patients who underwent curative treatment for esophageal cancer, including esophageal cancer surgery, in Sweden from 2001to 2005. The main outcome was HRQL summary score trajectories, measured by the well-validated EORTC QLQ-C30 questionnaire at 6 months, 3, 5, 10, and 15 years after esophagectomy, and analyzed using growth mixture models. Potentially underlying factors for these trajectories (age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications) were analyzed using weighted logistic regression providing odds ratios (OR) with 95% CI. Results: Four distinct HRQL summary score trajectories were identified: Persistently good, improving, deteriorating, and persistently poor. The odds of belonging to a persistently poor trajectory were decreased by longer education (&gt;12 years versus &lt;9 years: OR 0.18, 95% CI: 0.05–0.66) and adenocarcinoma histology (adenocarcinoma versus squamous cell carcinoma: OR 0.37, 95% CI: 0.16–0.85), and increased by more advanced pathological tumor stage (III–IV versus 0–I: OR 2.82, 95% CI: 1.08–7.41) and postoperative complications (OR 2.94, 95% CI: 1.36–6.36). Conclusion: Distinct trajectories with persistently poor or deteriorating HRQL were identified after curative treatment for esophageal cancer. Education, tumor histology, pathological tumor stage, and postoperative complications might influence HRQL trajectories. The results may contribute to a more tailored follow-up with timely and targeted interventions. Future research remains to confirm these findings.
Soft Bioelectronics for Neuroengineering: New Horizons in the Treatment of Brain Tumor and Epilepsy
Authors: Seungwon Yoo, Minjeong Kim, Changsoon Choi, Dae‐Hyeong Kim, Gi Doo Cha
Journal: Advanced Healthcare Materials (2023)

Soft bioelectronic technologies for neuroengineering have shown remarkable progress, which include novel soft material technologies and device design strategies. Such technological advances that are initiated from fundamental brain science are applied to clinical neuroscience and provided meaningful promises for significant improvement in the diagnosis efficiency and therapeutic efficacy of various brain diseases recently. System-level integration strategies in consideration of specific disease circumstances can enhance treatment effects further. Here, recent advances in soft implantable bioelectronics for neuroengineering, focusing on materials and device designs optimized for the treatment of intracranial disease environments, are reviewed. Various types of soft bioelectronics for neuroengineering are categorized and exemplified first, and then details for the sensing and stimulating device components are explained. Next, application examples of soft implantable bioelectronics to clinical neuroscience, particularly focusing on the treatment of brain tumor and epilepsy are reviewed. Finally, an ideal system of soft intracranial bioelectronics such as closed-loop-type fully-integrated systems is presented, and the remaining challenges for their clinical translation are discussed.
Predicting cytopenias, progression, and survival in patients with clonal cytopenia of undetermined significance: a prospective cohort study
Authors: Catherine Cargo, Elsa Bernard, Tumas Beinortas, Kelly L Bolton, Paul Glover, Helen Warren, Daniel Payne, Rukhsaar Ali, Alesia Khan, Mike Short, Suzan Van Hoppe, Alex Smith, Jan Taylor, Paul Evans, Elli Papaemmanuil, Simon Crouch
Journal: The Lancet Haematology (2023)