tbuckley/cabot-search huggingface dataset:
Diagnosis and management of resistant hypertension
Authors: Ernesto L Schiffrin, Naomi D L Fisher
Journal: BMJ (2024)

Abstract Resistant hypertension is defined as blood pressure that remains above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different classes, including a diuretic, with all agents administered at maximum or maximally tolerated doses. Resistant hypertension is also diagnosed if blood pressure control requires four or more antihypertensive drugs. Assessment requires the exclusion of apparent treatment resistant hypertension, which is most often the result of non-adherence to treatment. Resistant hypertension is associated with major cardiovascular events in the short and long term, including heart failure, ischemic heart disease, stroke, and renal failure. Guidelines from several professional organizations recommend lifestyle modification and antihypertensive drugs. Medications typically include an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a long acting thiazide-type/like diuretic; if a fourth drug is needed, evidence supports addition of a mineralocorticoid receptor antagonist. After a long pause since 2007 when the last antihypertensive class was approved, several novel agents are now under active development. Some of these may provide potent blood pressure lowering in broad groups of patients, such as aldosterone synthase inhibitors and dual endothelin receptor antagonists, whereas others may provide benefit by allowing treatment of resistant hypertension in special populations, such as non-steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease. Several device based approaches have been tested, with renal denervation being the best supported and only approved interventional device treatment for resistant hypertension.
Polymersomal Poly(I:C) Self‐Magnifies Antitumor Immunity by Inducing Immunogenic Cell Death and Systemic Immune Activation
Authors: Jingyi Wang, Beibei Guo, Zhiwei Sun, Songsong Zhao, Li Cao, Zhiyuan Zhong, Fenghua Meng
Journal: Advanced Healthcare Materials (2024)

Immunotherapy has emerged as a powerful weapon against lung cancer, yet only a fraction of patients respond to the treatment. Poly(I:C) (PIC) effectively triggers both innate and adaptive immunity. It can also induce immunogenic cell death (ICD) in tumor cells. However, its efficacy is hindered by its instability in vivo and limited cellular uptake. To address this, PIC is encapsulated in cRGD-functionalized polymersomes (t-PPIC), which significantly increases its stability and uptake, thus activating dendritic cells (DCs) and inducing apoptosis of lung tumor cells in vitro. In a murine LLC lung tumor model, systemic administration of t-PPIC effectively suppresses tumor growth and leads to survival benefits, with 40% of the mice becoming tumor-free. Notably, t-PPIC provokes stronger apoptosis and ICD in tumor tissue and elicits a more potent stimulation of DCs, recruitment of natural killer (NK) cells, and activation of CD8
Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome
Authors: Shucheng Si, Hongyan Liu, Lu Xu, Siyan Zhan
Journal: Genome Medicine (2024)

Abstract Background Chronic kidney disease (CKD) is a progressive disease for which there is no effective cure. We aimed to identify potential drug targets for CKD and kidney function by integrating plasma proteome and transcriptome. Methods We designed a comprehensive analysis pipeline involving two-sample Mendelian randomization (MR) (for proteins), summary-based MR (SMR) (for mRNA), and colocalization (for coding genes) to identify potential multi-omics biomarkers for CKD and combined the protein–protein interaction, Gene Ontology (GO), and single-cell annotation to explore the potential biological roles. The outcomes included CKD, extensive kidney function phenotypes, and different CKD clinical types (IgA nephropathy, chronic glomerulonephritis, chronic tubulointerstitial nephritis, membranous nephropathy, nephrotic syndrome, and diabetic nephropathy). Results Leveraging pQTLs of 3032 proteins from 3 large-scale GWASs and corresponding blood- and tissue-specific eQTLs, we identified 32 proteins associated with CKD, which were validated across diverse CKD datasets, kidney function indicators, and clinical types. Notably, 12 proteins with prior MR support, including fibroblast growth factor 5 (FGF5), isopentenyl-diphosphate delta-isomerase 2 (IDI2), inhibin beta C chain (INHBC), butyrophilin subfamily 3 member A2 (BTN3A2), BTN3A3, uromodulin (UMOD), complement component 4A (C4a), C4b, centrosomal protein of 170 kDa (CEP170), serologically defined colon cancer antigen 8 (SDCCAG8), MHC class I polypeptide-related sequence B (MICB), and liver-expressed antimicrobial peptide 2 (LEAP2), were confirmed. To our knowledge, 20 novel causal proteins have not been previously reported. Five novel proteins, namely, GCKR (OR 1.17, 95% CI 1.10–1.24), IGFBP-5 (OR 0.43, 95% CI 0.29–0.62), sRAGE (OR 1.14, 95% CI 1.07–1.22), GNPTG (OR 0.90, 95% CI 0.86–0.95), and YOD1 (OR 1.39, 95% CI 1.18–1.64,) passed the MR, SMR, and colocalization analysis. The other 15 proteins were also candidate targets (GATM, AIF1L, DQA2, PFKFB2, NFATC1, activin AC, Apo A-IV, MFAP4, DJC10, C2CD2L, TCEA2, HLA-E, PLD3, AIF1, and GMPR1). These proteins interact with each other, and their coding genes were mainly enrichment in immunity-related pathways or presented specificity across tissues, kidney-related tissue cells, and kidney single cells. Conclusions Our integrated analysis of plasma proteome and transcriptome data identifies 32 potential therapeutic targets for CKD, kidney function, and specific CKD clinical types, offering potential targets for the development of novel immunotherapies, combination therapies, or targeted interventions.
A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia
Authors: Yunfei Chen, Yanmei Xu, Huiyuan Li, Ting Sun, Xuan Cao, Yuhua Wang, Feng Xue, Wei Liu, Xiaofan Liu, Huan Dong, Rongfeng Fu, Xinyue Dai, Wentian Wang, Yueshen Ma, Zhen Song, Ying Chi, Mankai Ju, Wenjing Gu, Xiaolei Pei, Renchi Yang, Lei Zhang
Journal: New England Journal of Medicine (2024)

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells.
Development and validation of a clinical decision tool for preoperative micropapillary and solid pattern lung adenocarcinoma of CT≤2 cm
Authors: Zhen Gao, Shang Liu, Han Xiao, Meng Li, Wan-gang Ren, Zhen Fen, Lin Xu, Zhong-min Peng
Journal: International Journal of Surgery (2024)

Micropapillary (MP) and solid(S) pattern adenocarcinoma are highly malignant subtypes of lung adenocarcinoma. In today's era of increasingly conservative surgery for small lung cancer, effective preoperative identification of these subtypes is greatly important for surgical planning and long term survival of patients.
Mortality in relation to diabetes remission in Swedish Obese Subjects -a prospective cohort study
Authors: Lena M.S. Carlsson, Björn Carlsson, Peter Jacobson, Cecilia Karlsson, Johanna C. Andersson-Assarsson, Felipe M. Kristensson, Sofie Ahlin, Per-Arne Svensson, Magdalena Taube, Ingmar Näslund, Kristjan Karason, Markku Peltonen, Kajsa Sjöholm
Journal: International Journal of Surgery (2024)

Background: People with obesity and type 2 diabetes (T2D) have reduced life expectancy, partly explained by increased risk of cardiovascular diseases and cancer. Here, we examined whether 2-year diabetes remission after bariatric surgery or usual care is associated with long-term mortality. Materials and methods: This report includes 586 participants with obesity and concomitant T2D from the prospective Swedish Obese Subjects (SOS) cohort study; 338 underwent bariatric surgery and 248 received usual obesity care. At inclusion, age was 37–60 years and BMI ≥34 kg/m 2 in men and ≥38 kg/m 2 in women. Median follow-up was 26.2 years (interquartile range 22.7–28.7). Diabetes status was determined using self-reported data on diabetes medication and in-study measures of blood glucose and HbA1c. The study was cross-linked to Swedish national registers for data on morbidity, death, and emigration. Results: Overall, 284 participants, 71.9% of surgery and 16.5% of usual care patients were in remission at the 2-year examination. During follow-up, mortality rates were 16.6 deaths per 1000 person-years (95% CI: 13.7–20.1) in the remission subgroup and 26.0 deaths per 1000 person-years (95% CI:22.2–30.4) in the non-remission subgroup (adjusted hazard ratio (HR adj )=0.71, 95% CI:0.54–0.95, P =0.019). The adjusted median life expectancy in the remission subgroup was 2.5 years (95% CI:0.3–4.7) longer than in the non-remission subgroup. Specifically, remission was associated with decreased cardiovascular mortality (sub-HR adj =0.54, 95% CI: 0.35–0.85, P =0.008), but no detectable association with cancer mortality was found (sub-HR adj =1.06, 95% CI:0.60–1.86), P =0.841). Conclusion: In this post-hoc analysis of data from the SOS study, patients who achieved short-term diabetes remission had increased life expectancy and decreased cardiovascular death over up to 32 years of follow-up. Future studies should confirm these findings.
Development and validation of a deep learning model for predicting gastric cancer recurrence based on CT Imaging: a multicenter study
Authors: Mengxuan Cao, Can Hu, Feng Li, Jingyang He, Enze Li, Ruolan Zhang, Wenyi Shi, Yanqiang Zhang, Yu Zhang, Qing Yang, Qianyu Zhao, Lei Shi, Zhiyuan Xu, Xiangdong Cheng
Journal: International Journal of Surgery (2024)

The postoperative recurrence of gastric cancer has a significant impact on the overall prognosis of patients. Therefore, accurately predicting the postoperative recurrence of gastric cancer is crucial.
Commentary on: One-year results of the flowdynamics dense mesh stent for residual dissection after proximal repair of stanford type a or type b aortic dissection: a multicenter, prospective and randomized study
Authors: Tao Liu, Chenfan Guo, Pandeng Wang, Baoshi Zheng
Journal: International Journal of Surgery (2024)

aDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China bDepartment of Cardiothoracic Surgery, Guangxi International Zhuang Medicine Hospital, Guangxi University of Chinese Medicine, Nanning 530200, Guangxi, China This article does not refer to any raw data. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Guangxi Medical University First Affiliated Hospital: The First Affiliated Hospital of Guangxi Medical University CHINA. E-mail: [email protected] (B. Zheng). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Anatomical predispositions for silent cerebral infarction post carotid artery stenting: A retrospective cohort
Authors: Tianhua Li, Renjie Yang, Jie Wang, Tao Wang, Guangjie Liu, Jiaqi Jin, Xuesong Bai, Ran Xu, Taoyuan Lu, Yabing Wang, Adam A. Dmytriw, Bin Yang, Liqun Jiao
Journal: International Journal of Surgery (2024)

Background: Silent cerebral infarction (SCI) that manifests following carotid artery stenting (CAS) has been postulated to correlate with cognitive decline, the onset of dementia, and an increased risk of subsequent cerebrovascular events. This investigation aimed to thoroughly examine the potential anatomical predispositions that are linked to the occurrence of SCI post-CAS, and further develop a predictive nomogram that could accurately forecast the risk of SCI post-CAS. Methods: The present investigation conducted a retrospective examination of datasets from 250 individuals presenting with carotid artery stenosis who had been subjected to CAS within a tertiary healthcare institution from June 2020 to November 2021. Stratified by the procedural date, participants were allocated into a training cohort and a validation cohort. A nomogram was constructed predicated on salient prognostic determinants discerned via a multivariate logistic regression analysis. Results: An aggregate of 184 patients were incorporated into the study, of which 60 (32.6%) manifested SCI, whereas 124 (67.4%) did not. Within the training cohort (n=123), age (OR 1.08, 95%CI 1.01-1.16; P =0.034), aortic arch type (Type III vs. I: OR 10.79, 95%CI 2.12-54.81; P =0.005), aortic arch variant (OR 47.71, 95%CI 6.05-376.09; P &lt;0.001), common carotid artery (CCA) ostium lesions (OR 6.93, 95%CI 1.49-32.32; P =0.014), and proximal tortuosity index (TI) (OR 1.01, 95%CI 1.00-1.02; P =0.029) were demarcated as standalone risk predispositions for SCI subsequent to CAS. The concordance index (C-index) for the training cohort's nomogram stood at 0.89 (95% CI, 0.84-0.95). Moreover, the said nomogram exhibited commendable efficacy within the validation cohort (C-index=0.94) as well as the entire participant base (C-index=0.90). Furthermore, the decision curve analysis illustrated the exemplary clinical applicability of the nomogram. Conclusions: The findings of this inquiry underscore that age, aortic arch type, aortic arch variant, CCA ostium lesions, and proximal TI serve as independent determinants linked with SCI post-CAS. The formulated nomogram, predicated on these risk factors, possesses robust prognostic significance and might serve as a valuable adjunct to inform clinical decision-making.
Extracorporeal shock wave therapy with imaging examination for early osteonecrosis of the femoral head: a systematic review
Authors: Han Tan, Peiyuan Tang, Hua Chai, Wenbo Ma, Yangbin Cao, Bin Lin, Ying Zhu, Wenfeng Xiao, Ting Wen, Yusheng Li
Journal: International Journal of Surgery (2024)

Background: Extracorporeal shockwave therapy (ESWT) is a traditional non-invasive therapy to treat osteonecrosis of the femur head (ONFH). This systematic review aims to investigate whether ESWT can improve the clinical function of ONFH and whether differences in improvement can be observed in radiographic outcomes. Materials and methods: Two authors independently searched PubMed, Embase, Cochrane Library, and Web of Science for English articles until October 21, 2023. After screening and reading the literature, the two authors independently used corresponding scales to evaluate the quality of the included articles and extracted data. The key data extracted included the Harris Hip Score (HHS), Visual Analog Scale (VAS), changes in lesion size, the change in the Association Research Circulation Osseous (ARCO) stage, and bone marrow edema stage. Results: Nine articles included 468 males and 248 females. The average age was 43.29 years and the mean follow-up time was 15.19 months. After receiving ESWT, five studies involving 146 hips showed a higher HHS (MD=−33.38; 95%CI, -46.31, -20.45), and the difference was statistically significant ( P &lt;0.00001). The average VAS before treatment was above 5, but it dropped to 1.2 after ESWT (MD=4.64; 95%CI, 3.63, 5.64), and the difference was statistically significant ( P &lt;0.00001). Three studies found no significant differences in the areas of femoral head necrosis before and after treatment with ESWT(MD=9.66; 95%CI, -0.36, 19.67; P =0.06; I 2 =84%). Two articles showed that the use of ESWT had no significant effect on the change in the ARCO stage (MD=1.11; 95%CI, 0.76, 1.62; P =0.60; I 2 =0%). Three studies indicated that using ESWT could improve the bone marrow edema symptom in the early stage of ONFH (MD=4.35; 95%CI, 1.32, 14.37; P =0.02; I 2 =62%). Conclusion: Based on the current evidence, ESWT shows promise as a therapy to enhance hip function and alleviate pain in the early stage of ONFH. With the advancement of more precise imaging techniques, ESWT can potentially reduce the area affected by ONFH. However, such reduction was not found to be statistically significant at the imaging level. Additionally, ESWT could improve symptoms of bone marrow edema in the early stage. However, no significant change in ARCO grade was observed with ESWT treatment.
Electronic symptom monitoring after lung cancer surgery: establishing a core set of patient-reported outcomes for surgical oncology care in a longitudinal cohort study
Authors: Hongfan Yu, Cheng Lei, Xing Wei, Yaqin Wang, Wei Xu, Li Tang, Wei Dai, Jia Liao, Yang Pu, Ruoyan Gong, Xueyao Su, Yu Qingsong, Jiayuan Zhang, Lijun Zhang, Yanyan Huang, Xiang Zhuang, Jin Bai, Zhibiao Wang, Qiang Li, Qiuling Shi
Journal: International Journal of Surgery (2024)

Background: Electronic symptom monitoring via patient-reported outcomes in surgical oncology is limited owing to lengthy instruments and non-specific items in common patient-reported outcome instruments. To establish electronic symptom monitoring through a clinically relevant and fit-for-purpose core set of patient-reported outcome in patients undergoing lung cancer surgery. Materials and methods: One qualitative (Cohort 1) and two prospective studies (Cohorts 2 and 3) were conducted between 2018 and 2022. Patients undergoing lung cancer surgery were recruited. Items of symptoms and daily functioning were generated through extensive interviews in Cohort 1 and incorporated into a smartphone-based platform to establish the electronic Perioperative Symptom Assessment for Lung surgery (ePSA-Lung). This instrument was finalized and validated in Cohort 2. Patients in Cohort 3 were longitudinally monitored for the first-year post-surgery using the validated ePSA-Lung. Results: In total, 1037 patients scheduled for lung cancer surgery were recruited. The 11-item draft PSA-Lung was generated based on qualitative interview with 39 patients and input from a Delphi study involving 42 experts. A 9-item ePSA-Lung was finalized by assessing 223 patients in the validation cohort; the results supported the instrument’s understandability, reliability, sensitivity, and surgical specificity. In Cohort 3 ( n =775), compliance ranged from 63.21 to 84.76% during the 1-year follow-up after discharge. Coughing, shortness of breath, and disturbed sleep were the most severe symptoms after discharge. Longitudinally, patients who underwent single-port video-assisted thoracic surgery had a lower symptom burden than those who underwent multi-port video-assisted thoracic surgery or thoracotomy (all symptoms, P &lt;0.001). Conclusions: The ePSA-Lung is valid, concise, and clinically applicable as it supports electronic symptom monitoring in surgical oncology care. The need for long-term extensive care was identified for patients after discharge, even in early-stage cancer with potential curative treatment.
Sharing brain imaging data in the Open Science era: how and why?
Authors: Kathrin Giehl, Henk-Jan Mutsaerts, Kristien Aarts, Frederik Barkhof, Svenja Caspers, Gaël Chetelat, Marie-Elisabeth Colin, Emrah Düzel, Giovanni B Frisoni, M Arfan Ikram, Jorge Jovicich, Silvia Morbelli, Wolfgang Oertel, Christian Paret, Daniela Perani, Petra Ritter, Bàrbara Segura, Laura E M Wisse, Elke De Witte, Stefano F Cappa, Thilo van Eimeren
Journal: The Lancet Digital Health (2024)

The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.
PKD1 mutant clones within cirrhotic livers inhibit steatohepatitis without promoting cancer
Authors: Min Zhu, Yunguan Wang, Tianshi Lu, Jason Guo, Lin Li, Meng-Hsiung Hsieh, Purva Gopal, Yi Han, Naoto Fujiwara, Darren P. Wallace, Alan S.L. Yu, Xiangyi Fang, Crystal Ransom, Sara Verschleisser, David Hsiehchen, Yujin Hoshida, Amit G. Singal, Adam Yopp, Tao Wang, Hao Zhu
Journal: Cell Metabolism (2024)
Corrigendum to: “Circumventing drug resistance in gastric cancer: A spatial multi-omics exploration of chemo and immuno-therapeutic response dynamics” [Drug Resist Updates 74 (2024) 101080]
Authors: Gang Che, Jie Yin, Wankun Wang, Yandong Luo, Yiran Chen, Xiongfei Yu, Haiyong Wang, Xiaosun Liu, Zhendong Chen, Xing Wang, Yu Chen, Xujin Wang, Kaicheng Tang, Jiao Tang, Wei Shao, Chao Wu, Jianpeng Sheng, Qing Li, Jian Liu
Journal: Drug Resistance Updates (2024)
Targeting endothelial glycolytic reprogramming by tsRNA-1599 for ocular anti-angiogenesis therapy
Authors: Xiao-Yan Han, Ling-Jie Kong, Duo Li, Ming Tong, Xiu-Miao Li, Chen Zhao, Qin Jiang, Biao Yan
Journal: Theranostics (2024)

Current treatments for ocular angiogenesis primarily focus on blocking the activity of vascular endothelial growth factor (VEGF), but unfavorable side effects and unsatisfactory efficacy remain issues. The identification of novel targets for anti-angiogenic treatment is still needed.
Adeno-associated-virus-mediated delivery of CRISPR-CasRx induces efficient RNA knockdown in the mouse testis
Authors: Kai Li, Mengzhen Li, Yanyun Luo, Dingfeng Zou, Yahui Li, Xinyu Mang, Zexuan Zhang, Pengyu Li, Yan Lu, Shiying Miao, Wei Song
Journal: Theranostics (2024)

In male mammals, many developmental-stage-specific RNA transcripts (both coding and noncoding) are preferentially or exclusively expressed in the testis, where they play important roles in spermatogenesis and male fertility. However, a reliable platform for efficiently depleting various types of RNA transcripts to study their biological functions during spermatogenesis