tbuckley/cabot-search huggingface dataset:
Targeted dual degradation of HER2 and EGFR obliterates oncogenic signaling, overcomes therapy resistance, and inhibits metastatic lesions in HER2-positive breast cancer models
Authors: Lu Yang, Arup Bhattacharya, Darrell Peterson, Yun Li, Xiaozhuo Liu, Elisabetta Marangoni, Valentina Robila, Yuesheng Zhang
Journal: Drug Resistance Updates (2024)

Human epidermal growth factor receptor 2 (HER2) is an oncogenic receptor tyrosine kinase amplified in approximately 20% of breast cancer (BC). HER2-targeted therapies are the linchpin of treating HER2-positive BC. However, drug resistance is common, and the main resistance mechanism is unknown. We tested the hypothesis that drug resistance results mainly from inadequate or lack of inhibition of HER2 and its family member epidermal growth factor receptor (EGFR). We used clinically relevant cell and tumor models to assess the impact of targeted degradation of HER2 and EGFR on trastuzumab resistance. Trastuzumab is the most common clinically used HER2 inhibitor. Targeted degradation of HER2 and EGFR was achieved using recombinant human protein PEPDG278D, which binds to the extracellular domains of the receptors. siRNA knockdown was used to assess the relative importance of EGFR and HER2 in trastuzumab resistance. Both HER2 and EGFR are overexpressed in all trastuzumab-resistant HER2-positive BC cell and tumor models and that all trastuzumab-resistant models are highly vulnerable to targeted degradation of HER2 and EGFR. Degradation of HER2 and EGFR induced by PEPDG278D causes extensive inhibition of oncogenic signaling in trastuzumab-resistant HER2-positive BC cells. This is accompanied by strong growth inhibition of cultured cells, orthotopic patient-derived xenografts, and metastatic lesions in the brain and lung of trastuzumab-resistant HER2-positive BC. siRNA knockdown indicates that eliminating both HER2 and EGFR is necessary to maximize therapeutic outcome. This study unravels the therapeutic vulnerability of trastuzumab-resistant HER2-positive BC and shows that an agent that targets the degradation of both HER2 and EGFR is highly effective in overcoming drug resistance in this disease. The findings provide new insights and innovations for advancing treatment of drug-resistant HER2-positive breast cancer that remains an unmet problem.
Polyelectrolyte‐Cation Complexes Using PAsp‐Sr Complexes Induce Biomimetic Mineralization with Antibacterial Ability (Adv. Healthcare Mater. 7/2024)
Authors: Yuedan Xu, Dongni Shen, Zihuai Zhou, Yi Sun, Xinni Pan, Wei Liu, Chun Hung Chu, Ling Zhang, Matthias Hannig, Baiping Fu
Journal: Advanced Healthcare Materials (2024)
The selfish network: how the brain preserves behavioral function through shifts in neuronal network state
Authors: Albrecht Stroh, Susann Schweiger, Jan-Marino Ramirez, Oliver Tüscher
Journal: Trends in Neurosciences (2024)

Neuronal networks possess the ability to regulate their activity states in response to disruptions. How and when neuronal networks turn from physiological into pathological states, leading to the manifestation of neuropsychiatric disorders, remains largely unknown. Here, we propose that neuronal networks intrinsically maintain network stability even at the cost of neuronal loss. Despite the new stable state being potentially maladaptive, neural networks may not reverse back to states associated with better long-term outcomes. These maladaptive states are often associated with hyperactive neurons, marking the starting point for activity-dependent neurodegeneration. Transitions between network states may occur rapidly, and in discrete steps rather than continuously, particularly in neurodegenerative disorders. The self-stabilizing, metastable, and noncontinuous characteristics of these network states can be mathematically described as attractors. Maladaptive attractors may represent a distinct pathophysiological entity that could serve as a target for new therapies and for fostering resilience.
The role of the mitochondrial protein VDAC1 in inflammatory bowel disease: a potential therapeutic target
Authors: Ankit Verma, Srinivas Pittala, Belal Alhozeel, Anna Shteinfer-Kuzmine, Ehud Ohana, Rajeev Gupta, Jay H. Chung, Varda Shoshan-Barmatz
Journal: Molecular Therapy (2024)
mRNA vaccine platforms to prevent bacterial infections
Authors: Carson Bergstrom, Nicholas O. Fischer, Jessica Z. Kubicek-Sutherland, Zachary R. Stromberg
Journal: Trends in Molecular Medicine (2024)

Bacterial infections are an urgent public health priority. The application of mRNA vaccine technology to prevent bacterial infections is a promising therapeutic strategy undergoing active development. This article discusses recent advances and limitations of mRNA vaccines to prevent bacterial diseases and provides perspectives on future research directions.
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Journal: JAMA Surgery (2024)

Roger Olofsson Bagge, MD, PhD; Rasmus Mikiver, BS; Michael A. Marchetti, MD; Serigne N. Lo, PhD; Alexander C. J. van Akkooi, MD, PhD; Daniel G. Coit, MD; Christian Ingvar, MD, PhD; Karolin Isaksson, MD, PhD; Richard A. Scolyer, MD; John F. Thompson, MD; Alexander H. R. Varey, MD; Sandra L. Wong, MD; Johan Lyth, PhD; Edmund K. Bartlett, MD
Dermatology Images: Monkeypox
Authors: Andrés Grau-Echevarría, Rodrigo Peñuelas-Leal, Carolina Labrandero-Hoyos, Javier Lorca-Spröhnle, Daniel Blaya-Imbernón, Malena Finello, Amparo Pérez-Ferriols, Pablo Hernández-Bel
Journal: Journal of the American Academy of Dermatology (2024)
No impact of immunomodulatory treatments on SARS-CoV-2 (COVID-19) vaccine outcomes: A cross-sectional analysis of biologic and small molecule inhibitors used for psoriasis and hidradenitis suppurativa patients from the Epic Cosmos database
Authors: Bella R. Lee, Autumn R. Brostek, Benjamin H. Kaffenberger
Journal: Journal of the American Academy of Dermatology (2024)
Availability of drugs and resistance testing for bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaL(M)) regimen for rifampicin-resistant tuberculosis in Europe
Authors: Gunar Günther, Lorenzo Guglielmetti, Yousra Kherabi, Raquel Duarte, Christoph Lange
Journal: Clinical Microbiology and Infection (2024)
ESMO Clinical Practice Guideline interim update on first-line therapy in advanced urothelial carcinoma
Authors: T. Powles, J. Bellmunt, E. Comperat, M. De Santis, R. Huddart, Y. Loriot, A. Necchi, B.P. Valderrama, A. Ravaud, S.F. Shariat, B. Szabados, M.S. van der Heijden, S. Gillessen
Journal: Annals of Oncology (2024)
Accurate Spatio‐Temporal Delivery of Nitric Oxide Facilitates the Programmable Repair of Avascular Dense Connective Tissues Injury
Authors: Yubo Feng, Lefeng Su, Lei Liu, Zhanyi Chen, Yucheng Ji, Yuwei Hu, Dandan Zheng, Zhi Chen, Changbin Lei, He Xu, Yingchao Han, Hongxing Shen
Journal: Advanced Healthcare Materials (2024)

Abstract Avascular dense connective tissues (e.g., the annulus fibrosus (AF) rupture, the meniscus tear, and tendons and ligaments injury) repair remains a challenge due to the “biological barrier” that hinders traditional drug permeation and limits self‐healing of the injured tissue. Here, accurate delivery of nitric oxide (NO) to penetrate the “AF biological barrier” is achieved thereby enabling programmable AF repair. NO‐loaded BioMOFs are synthesized and mixed in a modified polyvinyl alcohol and PCL‐composited electrospun fiber membrane with excellent reactive oxygen species‐responsive capability (LN@PM). The results show that LN@PM could respond to the high oxidative stress environment at the injured tissue and realize continuous and substantial NO release. Based on low molecular weight and lipophilicity, NO could penetrate through the “biological barrier” for accurate AF drug delivery. Moreover, the dynamic characteristics of the LN@PM reaction can be matched with the pathological microenvironment to initiate programmable tissue repair including sequential remodeling microenvironment, reprogramming the immune environment, and finally promoting tissue regeneration. This tailored programmable treatment strategy that matches the pathological repair process significantly repairs AF, ultimately alleviating intervertebral disc degeneration. This study highlights a promising approach for avascular dense connective tissue treatment through intelligent NO release, effectively overcoming “AF biological barriers” and programmable treatment.
Artificial intelligence-assisted system for the assessment of Forrest classification of peptic ulcer bleeding: a multicenter diagnostic study
Authors: Xiao-Jian He, Xiao-Ling Wang, Tian-Kang Su, Li-Jia Yao, Jing Zheng, Xiao-Dong Wen, Qin-Wei Xu, Qian-Rong Huang, Li-Bin Chen, Chang-Xin Chen, Hai-Fan Lin, Yi-Qun Chen, Yan-Xing Hu, Kai-Hua Zhang, Chuan-Shen Jiang, Gang Liu, Da-Zhou Li, Dong-Liang Li, Wang Wen
Journal: Endoscopy (2024)

Abstract Background Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). Methods A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. Results The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%–92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%–97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. Conclusion The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.
Author Correction: Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial
Authors: Thomas A Wadden, Ariana M Chao, Sriram Machineni, Robert Kushner, Jamy Ard, Gitanjali Srivastava, Bruno Halpern, Shuyu Zhang, Jiaxun Chen, Mathijs C Bunck, Nadia N Ahmad, Tammy Forrester
Journal: Nature Medicine (2024)
Author Correction: Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans
Authors: Verena M Link, Poorani Subramanian, Foo Cheung, Kyu Lee Han, Apollo Stacy, Liang Chi, Brian A Sellers, Galina Koroleva, Amber B Courville, Shreni Mistry, Andrew Burns, Richard Apps, Kevin D Hall, Yasmine Belkaid
Journal: Nature Medicine (2024)
Greenhouse gas emissions associated with suboptimal asthma care in the UK: the SABINA healthCARe-Based envirONmental cost of treatment (CARBON) study
Authors: Alexander J K Wilkinson, Ekaterina Maslova, Christer Janson, Vasanth Radhakrishnan, Jennifer K Quint, Nigel Budgen, Trung N Tran, Yang Xu, Andrew Menzies-Gow, John P Bell
Journal: Thorax (2024)

Background Poorly controlled asthma is associated with increased morbidity and healthcare resource utilisation (HCRU). Therefore, to quantify the environmental impact of asthma care, this retrospective, cohort, healthCARe-Based envirONmental cost of treatment (CARBON) study estimated greenhouse gas (GHG) emissions in the UK associated with the management of well-controlled versus poorly controlled asthma. Methods Patients with current asthma (aged ≥12 years) registered with the Clinical Practice Research Datalink (2008‒2019) were included. GHG emissions, measured as carbon dioxide equivalent (CO 2 e), were estimated for asthma-related medication use, HCRU and exacerbations during follow-up of patients with asthma classified at baseline as well-controlled (&lt;3 short-acting β 2 -agonist (SABA) canisters/year and no exacerbations) or poorly controlled (≥3 SABA canisters/year or ≥1 exacerbation). Excess GHG emissions due to suboptimal asthma control included ≥3 SABA canister prescriptions/year, exacerbations and any general practitioner and outpatient visits within 10 days of hospitalisation or an emergency department visit. Results Of the 236 506 patients analysed, 47.3% had poorly controlled asthma at baseline. Scaled to the national level, the overall carbon footprint of asthma care in the UK was 750 540 tonnes CO 2 e/year, with poorly controlled asthma contributing excess GHG emissions of 303 874 tonnes CO 2 e/year, which is equivalent to emissions from &gt;124 000 houses in the UK. Poorly controlled versus well-controlled asthma generated 3.1-fold higher overall and 8.1-fold higher excess per capita carbon footprint, largely SABA-induced, with smaller contributions from HCRU. Conclusions These findings suggest that addressing the high burden of poorly controlled asthma, including curbing high SABA use and its associated risk of exacerbations, may significantly alleviate asthma care-related carbon emissions.
Multicenter prospective randomized controlled clinical trial comparing the pocket-creation method with and without single-clip traction of colonic endoscopic submucosal dissection
Authors: Takaaki Morikawa, Daiki Nemoto, Tomohiro Kurokawa, Takeshi Yamashina, Yoshikazu Hayashi, Masafumi Kitamura, Masahiro Okada, Takahito Takezawa, Yuki Nakajima, Yuka Kowazaki, Hisashi Fukuda, Tatsuma Nomura, Nikolaos Lazaridis, Noriyoshi Fukushima, Keijiro Sunada, Hironori Yamamoto
Journal: Endoscopy (2024)

Abstract Background The pocket-creation method (PCM) was developed to overcome the technical difficulties of endoscopic submucosal dissection (ESD), although opening the pocket remains challenging. We developed a novel technique of PCM with single-clip traction (PCM-CT), which uses a reopenable clip as a traction device to maintain stability during the procedure. No prospective study has compared the efficacy of PCM-CT and PCM. This study aimed to investigate the effectiveness of PCM-CT vs. PCM in a randomized controlled trial. Methods This randomized controlled clinical trial was conducted at four Japanese institutions. Patients with superficial colorectal neoplastic lesions were included following Japanese guidelines for colorectal cancer. Seven moderately experienced endoscopists performed the ESD procedures using either PCM-CT or PCM. Results 100 patients were enrolled in the study. Compared with PCM, PCM-CT achieved significantly faster mean (SD) dissection speed (21.4 [10.8] vs. 27.0 [14.5] mm2/min [95%CI 0.5 to 10.7], P = 0.03), and reduced the mean procedure time (81.8 [57.9] vs. 64.8 [47.6] minutes [95%CI –38.2 to 4.3], P = 0.12) and pocket-opening time (37.8 [33.0] vs. 30.0 [28.9] minutes [95%CI –20.2 to 4.6], P = 0.22). En bloc and R0 resection rates were not significantly different between the two groups (100% vs. 100%, P &gt;0.99; 100% vs. 96%, P = 0.50, respectively). No significant differences were observed in adverse events between the two groups. Conclusion ESD facilitated by the novel PCM-CT method appeared to be significantly faster than PCM. Both methods achieved high R0 resection rates.
Changes in the Workforce Characteristics of Providers Who Care for Adult Patients With Rheumatologic and Musculoskeletal Disease in the United States
Authors: Melissa L. Mannion, Fenglong Xie, John D. FitzGerald, Amanda Alexander, Amy Mudano, Yujie Su, Kenneth G. Saag, Jeffrey R. Curtis
Journal: Arthritis & Rheumatology (2024)

The aim of this study was to describe the adult rheumatology workforce in the United States, assess change in rheumatology providers over time, and identify variation in rheumatology practice characteristics.
A diagnostic performance study of the 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for patients with antiphospholipid syndrome from the Antiphospholipid Syndrome Chinese Collaborative cohort presenting with suspected antiphospholipid syndrome
Authors: Qingyi Lu, Yuzhou Gan, Zhongqiang Yao, Chun Li
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Association of Muscle Quality and Pain in Adults With Symptomatic Knee Osteoarthritis, Independent of Muscle Strength: Findings From a <scp>Cross‐Sectional</scp> Study
Authors: Alisa J. Johnson, Sarah M. Barron, Jennifer A. Nichols, Yenisel Cruz‐Almeida
Journal: Arthritis & Rheumatology (2024)

Objective Knee osteoarthritis (OA) is a leading cause of chronic pain in adults and shows wide interindividual variability, with peripheral and central factors contributing to the pain experience. Periarticular factors, such as muscle quality (eg, echo intensity [EI] and shear wave velocity [SWV]), may contribute to knee OA pain; however, the role of muscle quality in OA symptoms has yet to be fully established. Methods Twenty‐six adults (age &gt;50 years) meeting clinical criteria for knee OA were included in this cross‐sectional study. Quantitative ultrasound imaging was used to quantify EI and SWV in the rectus femoris of the index leg. Pearson correlations followed by multiple linear regression was used to determine associations between muscle quality and pain, controlling for strength, age, sex, and body mass index. Results EI and SWV were significantly associated with movement‐evoked pain (b = 0.452–0.839, P = 0.024–0.029). Clinical pain intensity was significantly associated with SWV (b = 0.45, P = 0.034), as were pressure pain thresholds at the medial (b = −0.41, P = 0.025) and lateral (b = −0.54, P = 0.009) index knee joint line, adjusting for all covariates. Pain interference was significantly associated with knee extension strength (b = −0.51, P = 0.041). Conclusion These preliminary findings suggest that EI and SWV may impact knee OA pain and could serve as malleable treatment targets. Findings also demonstrate that muscle quality is a unique construct, distinct from muscle strength, which may impact pain and treatment outcomes. More research is needed to fully understand the role of muscle quality in knee OA.
Underwater coagulation using hybrid knife in peroral endoscopic myotomy for achalasia
Authors: Antonio Capogreco, Roberto de Sire, Davide Massimi, Ludovico Alfarone, Roberta Maselli, Cesare Hassan, Alessandro Repici
Journal: Endoscopy (2024)

Achalasia is an idiopathic esophageal motility disorder, characterized by the insufficient relaxation of the lower esophageal sphincter and the absence of peristalsis in the esophageal body, leading to disabling symptoms, such as dysphagia, regurgitation, chest pain, and weight loss [1]. Until a few years ago, common interventional therapeutic approaches included botulinum toxin injection, endoscopic pneumatic balloon dilation, and laparoscopic Heller myotomy. Nevertheless, the first options have proved to be of only limited efficacy, while the surgical approach is highly invasive, costly, and burdened by potential severe complications and long recovery times [2].
Endoscopic removal of a whole ascaris from the colonic lumen
Authors: Cheng Guo, Wei Liu, Yijun Wang, Tao Chen, Meidong Xu
Journal: Endoscopy (2024)

A 67-year-old previous healthy woman was admitted to our hospital with paroxysmal abdominal colic. She reported that she loved eating raw food. She underwent colonoscopy, which revealed a reddish white, cylindrical ascaris with horizontal stripes wriggling vigorously in the lumen of the ascending colon ([Fig. 1] a). We used forceps to grab the middle of the live ascaris and pull it out of the patient's body under direct visualization ([Fig. 1] b; [Video 1]). The ascaris was found to be more than 20 cm long ([Fig. 2]).
Endoscopic radial incision of a congenital antral web in a child
Authors: Nuoya Zhou, Ou Chen, Xianglei Yuan, Bing Hu
Journal: Endoscopy (2024)

A 5-year-old boy presented with intermittent nonbilious vomiting for over 1 year. During the gastroscopy examination, an antral web with a central aperture was found with the pylorus visible in the distance ([Fig. 1]). A barium swallow test showed narrowing in the area of antrum and pylorus, but the contrast agent could still pass through ([Fig. 2]). The definitive diagnosis of "congenital antral web, incomplete antral web" was made. Endoscopic treatment was subsequently performed ([Fig. 3], [Video 1]). The web was incised directly using an insulated-tipped knife (Olympus, Tokyo, Japan) in a radial pattern at eleven, three, and seven o'clock until the circular muscle was completely cut, clearly exposing the antrum and pylorus. The endoscope was able to pass the pylorus smoothly after the incision. The patient was discharged in stable condition after 6 days without any adverse events. The patient's symptoms were significantly resolved and a follow-up endoscopy at 6 months suggested good wound healing and widened aperture of the residual web ([Fig. 4]).
Biliary ascariasis: extraction
Authors: Muhammad Rahimi, Ikhwan Sani Mohamad, Maya Mazuwin Yahya, Mohd Azem Fathi Mohammad Azmi, Leow Voon Meng
Journal: Endoscopy (2024)

Biliary ascariasis is one of the complications of Ascaris lumbricoides infestation. The condition results from the migration of the A. lumbricoides worm into the biliary tract, causing symptoms ranging from mild biliary colic to severe cholangitis [1]. Despite A. lumbricoides being one of the most common helminth infestations in Malaysia, biliary ascariasis is rare [2].
Cholangioscopy findings of biliary candidiasis post-liver transplantation
Authors: Da Yeon Ryoo, Sylvester M. Black, Ashley Limkemann, Shaoli Sun, Nicole Gray, Samuel Han
Journal: Endoscopy (2024)

Solid organ transplant patients are often subject to immunosuppressive agents, which predispose them to opportunistic infections. Of those infectious agents, fungal infections such as Candida are associated with the highest mortality rate [1].
A rare case of endoscopic full-thickness resection of a laterally spreading tumor at the anastomotic site of appendectomy
Authors: Yinong Zhu, Wei Liu, Bing Hu
Journal: Endoscopy (2024)

A 67-year-old man who had undergone an appendectomy 20 years ago was admitted owing to the presence of a laterally spreading tumor (LST) at the anastomotic site of the previous surgery ([Fig. 1] a, [Video 1]). After a thorough preoperative examination and considering the inherent difficulty of performing endoscopic submucosal dissection (ESD) at the appendiceal orifice and the additional challenge posed by surgical anastomotic scar adhesions, endoscopic full-thickness resection (EFTR) was chosen as the treatment modality. During the procedure, a C-shaped incision revealed a severe postoperative tissue adhesion ([Fig. 1] b), confirming the difficulty associated with ESD. Utilizing the initial C-shaped incision, partial dissection of the submucosal layer was performed, followed by a circumferential incision of the lesion mucosa using the DualKnife (Olympus, Tokyo, Japan). After that, an IT knife (Olympus) was used to complete the endoscopic full-thickness resection. The defect was closed using nylon cords (Micro-Tech, Nanjing, China) and 14 titanium clips ([Fig. 1] c, [Fig. 1] d). The patient was discharged 4 days after the treatment, and the pathology revealed a tubular adenoma.