tbuckley/cabot-search huggingface dataset:
Adsorbed polymer conjugates to adaptively inhibit blood coagulation activation by medical membranes
Authors: Tina Helmecke, Dominik Hahn, André Ruland, Mikhail V. Tsurkan, Manfred F. Maitz, Carsten Werner
Journal: Journal of Controlled Release (2024)

Adaptive drug release can combat coagulation and inflammation activation at the blood-material interface with minimized side effects. For that purpose, poly(styrene-alt-maleic-anhydride) copolymers were conjugated to heparin via coagulation-responsive linker peptides and shown to tightly adsorb onto poly(ethersulfone) (PES)-surfaces from aqueous solutions as monolayers. Coagulation-responsive release of unfractionated as well as low molecular weight heparins from the respective coatings was demonstrated to be functionally beneficial in human plasma and whole blood incubation with faster release kinetics resulting in stronger anticoagulant effects. Coated poly(ethersulfone)/poly(vinylpyrrolidone) (PES/PVP) flat membranes proved the technology to offer an easy, effective and robust anticoagulant interfacial functionalization of hemodialysis membranes. In perspective, the modularity of the adaptive release system will be used for inhibiting multiple activation processes.
Anatomic Subtype Differences in Extramammary Paget Disease
Authors: Nour Kibbi, Joshua L. Owen, Brandon Worley, Jake X. Wang, Vishnu Harikumar, Sumaira Z. Aasi, Sunandana Chandra, Jennifer N. Choi, Yasuhiro Fujisawa, Christos Iavazzo, John Y. S. Kim, Naomi Lawrence, Mario M. Leitao, Allan B. MacLean, Jeffrey S. Ross, Anthony M. Rossi, Sabah Servaes, Michael J. Solomon, Murad Alam
Journal: JAMA Dermatology (2024)

Extramammary Paget disease (EMPD) is a rare, highly recurrent cutaneous malignant neoplasm of unclear origin. EMPD arises most commonly on the vulvar and penoscrotal skin. It is not presently known how anatomic subtype of EMPD affects disease presentation and management.
Personalized circulating tumor DNA monitoring improves recurrence surveillance and management after curative resection of colorectal liver metastases: a prospective cohort study
Authors: Yaqi Li, Jing Xu, Xiang Hu, Yikuan Chen, Fangqi Liu, Yun Chen, Xiaoji Ma, Qiduo Dong, Lei Sun, Shaobo Mo, Long Zhang, Xingfeng He, Shanyou Tong, Huizi Wu, Wenhua Li, Sanjun Cai, Shida Zhu, Qi Pan, Junjie Peng
Journal: International Journal of Surgery (2024)

Background: Approximately 60% of patients with CRLM experience relapse within 2 years after radical resection, previous studies have proven that repeat local treatment (LT) could prolong survival, however, it is difficult to seize the window for LT due to the lack of a high-sensitive surveillance method. In this study, we aim to examine the value of longitudinal circulating tumor DNA (ctDNA) in guiding adjuvant chemotherapy (ACT), optimizing clinical surveillance strategy, and thereby improving CRLM outcomes. Materials and Methods: We conducted a prospective clinical trial using a personalized, tumor-informed ctDNA assay to monitor 60 CRLM patients undergoing resection with curative intent. Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected after surgery. Blood samples were collected before surgery, 30 days after surgery (post-OP), and every third month until relapse or up to 2 years. Results: A total of 394 plasma samples from 60 eligible patients were analyzed, with a median follow-up time of 31.3 months. Landmark analyses revealed that detectable ctDNA at post-OP (HR, 4.8), post-ACT (HR, 6.0), and end-of-treatment (EOT) (HR, 5.6) were associated with higher recurrence risk ( P &lt; 0.001). Post-OP ctDNA positivity served as the only independent prognostic marker in the multivariant analysis (HR, 5.1; P &lt; 0.001). Longitudinal ctDNA analysis identified relapsed patients at both sensitivity and specificity of 100%. Most (75%) patients were found with radiological relapse within 6 months after the first detectable ctDNA with a median lead time of 3.5 months. In relapsed patients, 73.2% had oligometastatic disease and 61% were liver-restricted, of which 72.0% received repeat LTs, and 60.0% achieved a secondary no evidence of disease (NED) status. Conclusions: Longitudinal ctDNA monitoring assists in early prediction of relapse, and thereby improves survival of CRLM patients by increased secondary resection rate and secondary NED rate.
A commentary on ‘High ligation of the anal fistula tract by lateral approach: A prospective cohort study on a modification of the ligation of the intersphincteric fistula tract technique’
Authors: Shiwei Yang, Liwei Yan, Keliang Jia, Chao Gu, Guang Zhang
Journal: International Journal of Surgery (2024)

aDepartment of General Surgery, The First Affiliated Hospital of Shandong First Medical University,Jinan 250014,Shandong,China bDepartment of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China cDepartment of Health Management, The First Affiliated Hospital of ShandongFirst Medical University ,Jinan 250014,Shandong,China #Co-authors: Shiwei Yang and Liwei Yan equally contributed to the article. 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 Health Management, The First Affiliated Hospital of ShandongFirst Medical University ,Jinan 250014,Shandong,China. E-mail address: [email protected] (G. Zhang). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort
Authors: Sindhu Pandurangi, Reena Mourya, Shreya Nalluri, Lin Fei, Shun Dong, Sanjiv Harpavat, Stephen L. Guthery, Jean P. Molleston, Philip Rosenthal, Ronald J. Sokol, Kasper S. Wang, Vicky Ng, Estella M. Alonso, Evelyn K. Hsu, Saul J. Karpen, Kathleen M. Loomes, John C. Magee, Benjamin L. Shneider, Simon P. Horslen, Jeffrey H. Teckman, Jorge A. Bezerra
Journal: Hepatology (2024)

Background and Aims: High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated the accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort. Approach and Results: MMP-7 was measured in serum samples of 399 infants with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays. The discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an AUROC of 0.90 (CI: 0.87–0.94). At cutoff 52.8 ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77–0.86), stool color = 0.68 (CI: 0.63–0.73), and pathology = 0.84 (CI: 0.76–0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+gamma-glutamyl transferase AUROC to 0.91 (CI: 0.88–0.95). Serum concentrations produced by time resolved fluorescence energy transfer differed from single-plex, with an optimal cutoff of 18.2 ng/mL. Results were consistent within each assay technology and generated similar AUROCs. Conclusions: Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in the evaluation of infants with cholestasis may simplify diagnostic algorithms and shorten the time to hepatoportoenterostomy.
Macro-clusters: CD301b+ DCs prime Th2 responses
Authors: Hanna Abberger, Joanna R. Groom
Journal: The Journal of Experimental Medicine (2024)

In this issue of JEM, Lyons-Cohen et al. (https://doi.org/10.1084/jem.20231282) reveal that lymph node macro-clusters provide a spatial niche where CD301b+ cDC2s and CD4+ T cells interact. These integrin-mediated cellular hubs promote enhanced co-stimulation and cytokine signaling to drive Th2 differentiation.
Analyzing circulating tumor cells and epithelial-mesenchymal transition status of papillary thyroid carcinoma patients following thyroidectomy: a prospective cohort study
Authors: Hyeong Won Yu, Eunju Park, Ja Kyung Lee, Woochul Kim, Ju Hyun Kong, Joseph Sunoo, Soon-Cheol Hong, June Young Choi
Journal: International Journal of Surgery (2024)

Background: This study investigated the prevalence and subtype distribution of circulating tumor cells (CTCs) in patients with papillary thyroid cancer (PTC) before and after thyroidectomy to determine the potential of CTC count as a non-invasive marker of the efficacy of surgical treatment in PTC. Materials and Methods: Between January 2021 and January 2022, 62 PTC patients who underwent thyroidectomy at OOOOOOO Hospital were prospectively evaluated. Peripheral blood samples (7.5 ml) were collected from each patient for CTC analysis before surgery and at 2 weeks and 3 months after surgery. CTC count and the distribution of CTC subtypes, including epithelial, epithelial-mesenchymal, and mesenchymal phenotypes, were analyzed using the negative selection method and immunofluorescence staining. The relationship between CTC count and clinicopathological characteristics was analyzed before and after surgery. Results: Before surgery, CTCs were detected in 87% (54/62) of patients; the mean CTC count was 8.0 and the median was 5.0 in 7.5 ml of peripheral blood. The mesenchymal or epithelial-mesenchymal phenotypes were predominant. After thyroidectomy, the mean and median CTC count values decreased to 5.3 and 2.5, respectively, at 2 weeks and to 4.3 and 3.0, respectively, at 3 months. This postoperative reduction in CTCs was more pronounced in patients with lymphatic invasion, lymph node metastasis, or BRAF V600E mutation. Conclusion: CTCs were detected in patients with PTC with a predominance of cells undergoing epithelial-mesenchymal transition. The CTC count decreased postoperatively, suggesting that liquid biopsy with CTC detection could be a valuable non-invasive tool for monitoring the efficacy of surgery in PTC.
VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model
Authors: Ligia Simoes Braga Boisserand, Luiz Henrique Geraldo, Jean Bouchart, Marie-Renee El Kamouh, Seyoung Lee, Basavaraju G. Sanganahalli, Myriam Spajer, Shenqi Zhang, Sungwoon Lee, Maxime Parent, Yuechuan Xue, Mario Skarica, Xiangyun Yin, Justine Guegan, Kevin Boyé, Felipe Saceanu Leser, Laurent Jacob, Mathilde Poulet, Mingfeng Li, Xiodan Liu, Sofia E. Velazquez, Ruchith Singhabahu, Mark E. Robinson, Michael H. Askenase, Artem Osherov, Nenad Sestan, Jiangbing Zhou, Kari Alitalo, Eric Song, Anne Eichmann, Lauren H. Sansing, Helene Benveniste, Fahmeed Hyder, Jean-Leon Thomas
Journal: The Journal of Experimental Medicine (2024)

Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intracerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon cauterization of the dCLN afferent lymphatics and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke.
Whether surgical procedure can improve the prognosis of endometrial cancer arising in adenomyosis (EC-AIA)? A systematic review and meta-analysis
Authors: Yi Sun, Shitong Lin, Weijia Wu, Fangfang Nie, Yuchen Liu, Jing Wen, Xiaoran Cheng, Qianwen Liu, Yuanpei Wang, Fang Ren
Journal: International Journal of Surgery (2024)

Purpose: Endometrial cancer arising in adenomyosis (EC-AIA) is frequently detected accidentally following a general hysterectomy for adenomyosis. Whether supplemental lymphadenectomy in patients with EC-AIA can improve the survival outcome remains inconclusive. Herein, we summarized the data of patients with EC-AIA and further explored the impact of lymphadenectomy on the prognosis of these patients. Methods: Five electronic databases, namely MEDLINE, Web of Science, PubMed, Embase, and the Cochrane Library were employed for searching articles from inception to May 2023. Results: In total, 38 eligible studies enrolling 56 patients were included. Of these, 44 patients had a traceable prognosis. Kaplan–Meier curves demonstrated that patients who had undergone lymphadenectomy had a better progression-free survival (PFS) compared with those who had not undergone lymphadenectomy ( P =0.016), but there was no difference in overall survival (OS). Univariable ( P =0.025, HR=0.25, 95%CI=0.08–0.84) and multivariable ( P =0.042, HR=0.13, 95%CI=0.020–0.930) Cox regression analyses revealed that lymphadenectomy was an independent protective factor for PFS. Conclusion: For patients diagnosed with EC-AIA following hysterectomy for benign disease, further supplementary lymphadenectomy is recommended to improve PFS.
Open-door policy versus treatment-as-usual in urban psychiatric inpatient wards: a pragmatic, randomised controlled, non-inferiority trial in Norway
Authors: Anne-Marthe Rustad Indregard, Hans Martin Nussle, Milada Hagen, Per Olav Vandvik, Martin Tesli, Jakov Gather, Nikolaj Kunøe
Journal: The Lancet Psychiatry (2024)
Immunogenicity and safety of a bivalent (omicron BA.5 plus ancestral) SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose: interim analysis of a phase 3, non-inferiority, randomised, clinical trial
Authors: Chijioke Bennett, Wayne Woo, Mark Bloch, King Cheung, Paul Griffin, Rahul Mohan, Sachin Deshmukh, Mark Arya, Oscar Cumming, A Munro Neville, Toni G McCallum Pardey, Joyce S Plested, Shane Cloney-Clark, Mingzhu Zhu, Raj Kalkeri, Nita Patel, Alex Marcheschi, Jennifer Swan, Gale Smith, Iksung Cho, Gregory M Glenn, Robert Walker, Raburn M Mallory, Anna Anderson, Mary Ang, Timothy Barnes, Michelle Bassin, Kate Bessey, Simon Bowler, Sheetal Bull, Lucy Burr, Robert Burton, Michelle Byrne, Robert Carroll, Nicholas Chee, Aaron Choy, Malcolm Clark, Marije Dalebout, Peter De Wet, Kshama Deshmukh, Sergio Diez Alvarez, Dominic Douglas, Jacqueline Engelander, Carla Evangelista, Stuart Game, Noor Glass, Elizabeth Gunner, Jennifer Han, Michael Harrison, Jason Doong Hing Kiang, Thazin Hlaing, Divyansh Joshi, Sheree Joyce, Karen Kaluhin, Milanka Kavic, Juliana Kononov, Gary Lee, Wei-I Lee, Indika Leelasena, Esmond Leong, Ivan Lim, Graham Lister, Denissa Loh, Mary Magdy, Callum Maggs, Amith Mammoottil, Shannon McCarthy, Nicole McKay, Mariah Melek, Adrian Michael Barnett, Rahul Mohan, Andrew Moore, Amanda Moore, Louise Murdoch, Fiona Napier-Flood, Ushma Narsai, Alexander Neville, Paul Nguyen, Ekaterina Odarchenko, Toni Pardey, Dick Quan, Ushank Ranagsinghe, Roy Rasalam, Shiva Rayar, Gonasagaran Jay Ruthnam, Pi Seet, Deon Smith, Krishna Srilakshmanan, Angela Taggart, Florence Tiong, Boon Toh, Eniko Ujvary, Stephanie Wallace, Rebecca Wolf, Ian Wong, Hye Yoo, Rhys Young
Journal: The Lancet Infectious Diseases (2024)

SARS-CoV-2 variants evade immunity despite vaccination with prototype COVID-19 vaccines or previous infection. The 2019nCoV-311 (part 2) study is evaluating immune responses after two booster doses of a vaccine containing the omicron BA.5 subvariant spike protein in adults previously vaccinated with a prototype mRNA vaccine. This interim analysis reports on day 28 immunogenicity and safety outcomes after one booster dose.
Undiagnosed type 2 diabetes: an invisible risk factor
Authors: None The Lancet Diabetes & Endocrinology
Journal: The Lancet Diabetes & Endocrinology (2024)

There are diseases that puzzle doctors. Patients with these diseases often remain undiagnosed for years and some will die without an accurate diagnosis. The diagnosis of patients with mysterious diseases, many of which are rare diseases, can entail a long, complex, and detailed process that requires specialist knowledge and investigations. Patients and families often have a sense of relief upon receiving a diagnosis. A diagnosis can reduce uncertainty and fear and is essential to ensure appropriate medical treatment (if available), support, and health-care coverage.
Alzheimer’s Disease — Anti-Amyloid Medications, Early Detection, and Screening
Authors: Nathaniel A Chin, Debra Dinsmore, Tony Gonzales, Betsy Groves, DeLois Johnson, Julia Napolitano, Allan Ropper, Stephen Salloway, Lori Weiss
Journal: New England Journal of Medicine (2024)

In this Double Take video from the New England Journal of Medicine, Drs. Nathanial Chin and Stephen Salloway review the pathophysiology of Alzheimer's disease and discuss how anti-amyloid medications can help in early stages of the disease. The video notes disparities in diagnosis and treatment of Alzheimer's disease and provides guidance on screening and diagnosis and on which patients should be referred to specialty care. A related podcast, referenced in the video, is available at NEJM.org: Intention to Treat, episode 20: Alzheimer's Update, Part 1 (November 9, 2023).
Peeling and Plummeting
Authors: Caoilfhionn M Connolly, Monica Meeks, Avi Z Rosenberg, Jacqueline E Birkness-Gartman, Allan C Gelber
Journal: New England Journal of Medicine (2024)

A 20-year-old Guatemalan woman who had immigrated to Maryland 6 years earlier presented with a 6-month history of progressive pain and swelling in the hands, wrists, and ankles. Other symptoms included unintentional weight loss.
Platinum Nanoparticles‐Enhanced Ferritin–Mn<sup>2+</sup> Interaction for Magnetic Resonance Contrast Enhancement and Efficient Tumor Photothermal Therapy
Authors: Shuangqing Liu, Liya Tian, Mengyao Mu, Ziyan Liu, Mengzhen Dong, Yufang Gong, Hui Liu, Ximing Wang, Qingwei Meng, Haidong Zhang, Xiao Sun
Journal: Advanced Healthcare Materials (2024)

Nanoplatforms with high Mn
Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency–related cholestasis
Authors: Bikrant Bihari Lal, Seema Alam, Anupam Sibal, Karunesh Kumar, Somashekara Hosaagrahara Ramakrishna, Vaibhav Shah, Nirmala Dheivamani, Ashish Bavdekar, Aabha Nagral, Nishant Wadhwa, Arjun Maria, Aashay Shah, Ira Shah, Zahabiya Nalwalla, Pandey Snehavardhan, K.P. Srikanth, Subhash Gupta, Viswanathan M. Sivaramakrishnan, Yogesh Waikar, Arya Suchismita, A. Ashritha, Vikrant Sood, Rajeev Khanna
Journal: Hepatology (2024)

The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency.
Scale‐Up Preparation of Manganese‐Iron Prussian Blue Nanozymes as Potent Oral Nanomedicines for Acute Ulcerative Colitis
Authors: Chengyun Hu, Xue Yuan, Ronghua Zhao, Biao Hong, Chuang Chen, Qingjun Zhu, Yanmin Zheng, Jinming Hu, Yue Yuan, Zhengyan Wu, Jia Zhang, Chaoliang Tang
Journal: Advanced Healthcare Materials (2024)

Abstract Prussian blue (PB) nanozymes are demonstrated as effective therapeutics for ulcerative colitis (UC), yet an unmet practical challenge remains in the scalable production of these nanozymes and uncertainty over their efficacy. With a novel approach, a series of porous manganese‐iron PB (MnPB) colloids, which are shown to be efficient scavengers for reactive oxygen species (ROS) including hydroxyl radical, superoxide anion, and hydrogen peroxide, are prepared. In vitro cellular experiments confirm the capability of the nanozyme to protect cells from ROS attack. In vivo, the administration of MnPB nanozyme through gavage at a dosage of 10 mg kg −1 per day for three doses in total potently ameliorates the pathological symptoms of acute UC in a murine model, resulting in mitigated inflammatory responses and improved viability rate. Significantly, the nanozyme produced at a large scale can be achieved at an unprecedented yield weighting ≈11 g per batch of reaction, demonstrating comparable anti‐ROS activities and treatment efficacy to its small‐scale counterpart. This work represents the first demonstration of the scale‐up preparation of PB analog nanozymes for UC without compromising treatment efficacy, laying the foundation for further testing of these nanozymes on larger animals and promising clinical translation.
Back to the Future in Alabama
Authors: R Alta Charo
Journal: New England Journal of Medicine (2024)

Audio Interview Interview with R. Alta Charo on the potential implications of the Alabama Supreme Court's decision in LePage v. Center for Reproductive Medicine. 14m 12s Download AbstractAn Alabama Supreme Court decision about frozen embryos may trigger a wave of activism that sends much of the country back to the 1980s, as abortion politics again force women to endure substandard care.
Enfortumab Vedotin and Pembrolizumab — A New Perspective on Urothelial Cancer
Authors: Günter Niegisch
Journal: New England Journal of Medicine (2024)

For several decades, platinum-based chemotherapy has been the standard first-line option for patients with advanced inoperable or metastatic (or both) urothelial carcinoma. This paradigm, in which platinum-based chemotherapy was considered to be the only effective first-line chemotherapy, was implemented in the 1980s1 and remained unchanged even after immune checkpoint inhibitors were introduced in recent years as part of the treatment regimen for metastatic urothelial carcinoma. Treatment advances were made by replacing older treatments with less toxic combinations (e.g., gemcitabine and cisplatin2) or by replacing cisplatin with carboplatin in patients who were ineligible to receive cisplatin3 rather than by improving treatment . . .
Predictive factors for decompensating events in patients with cirrhosis with primary biliary cholangitis under different lines of therapy
Authors: Javier Ampuero, Ana Lucena, Marina Berenguer, Manuel Hernández-Guerra, Esther Molina, Judith Gómez-Camarero, Carlos Valdivia, Elena Gómez, Marta Casado, Carmen Álvarez-Navascuez, Francisco Jorquera, Luisa García-Buey, Álvaro Díaz-González, Rosa Morillas, Montserrat García-Retortillo, Jose M. Sousa, Indhira Pérez-Medrano, Miguel Á. Simón, Javier Martínez, Juan Arenas, María Carlota Londoño, Antonio Olveira, Conrado Fernández-Rodríguez
Journal: Hepatology (2024)

The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients.