tbuckley/cabot-search huggingface dataset:
Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma
Authors: Karisa C. Schreck, Roy E. Strowd, Louis B. Nabors, Benjamin M. Ellingson, Michael Chang, Sze K. Tan, Zied Abdullaev, Rust Turakulov, Kenneth Aldape, Neeraja Danda, Serena Desideri, Joy Fisher, Michaella Iacoboni, Trisha Surakus, Michelle A. Rudek, Chetan Bettegowda, Stuart A. Grossman, Xiaobu Ye
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Although fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600–mutated HGG. Patients and Methods: In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles. Eligible patients were required to have HGG or glioblastoma with a BRAF-V600E alteration that was recurrent following at least one line of therapy, including radiotherapy. Results: Five patients enrolled between January 2020 and administrative termination in November 2021 (due to closure of the ABTC). Enrolled patients received treatment for 2 to 40 months; currently one patient remains on treatment. Centrally determined radiographic response rate was 60%, with one complete response and two partial responses. Methylation profiling revealed that all tumors cluster most closely with anaplastic pleomorphic xanthoastrocytoma (PXA). Transcriptional profile for MAPK-response signature was similar across all tumors at baseline and did not correlate with response in this small population. Circulating tumor DNA measured in plasma samples before treatment, during response, and upon progression showed feasibility of detection for the BRAF-V600E alteration. No new safety signal was detected. Conclusions: Encorafenib and binimetinib exhibit positive tumor responses in patients with recurrent BRAF-V600E mutant HGG in this small series, warranting therapeutic consideration. Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients.
Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk
Authors: Duc Tran, J. Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C.C. Chan, Zilan Xin, Michael H. Kramer, Armel L. Batchi-Bouyou, Xiaoyu Zong, Matthew J. Walter, Giulia E.M. Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T. Oh, Daniel C. Link, Ben Busby, Yin Cao, Kelly L. Bolton
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet, our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development. Experimental Design: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard regression was used to test for an association between plasma protein levels and MN risk. Results: We identified 115 proteins associated with MN risk, of which 30% (N = 34) were also associated with CH. These were enriched for known regulators of the innate and adaptive immune system. Plasma proteomics improved the prediction of MN risk (AUC = 0.85; P = 5×10–9) beyond clinical factors and CH (AUC = 0.80). In an independent group (N = 381,485), we used inherited polygenic risk scores (PRS) for plasma protein levels to validate the relevance of these proteins toMNdevelopment. PRS analyses suggest that most MN-associated proteins we identified are not directly causally linked toMN risk, but rather represent downstream markers of pathways regulating the progression of CH to MN. Conclusions: These data highlight the role of immune cell regulation in the progression of CH to MN and the promise of leveraging multi-omic characterization of CH to improveMN risk stratification. See related commentary by Bhalgat and Taylor, p. 3095
Contextualizing remote fall risk: Video data capture and implementing ethical AI
Authors: Jason Moore, Peter McMeekin, Thomas Parkes, Richard Walker, Rosie Morris, Samuel Stuart, Victoria Hetherington, Alan Godfrey
Journal: npj Digital Medicine (2024)

Abstract Wearable inertial measurement units (IMUs) are being used to quantify gait characteristics that are associated with increased fall risk, but the current limitation is the lack of contextual information that would clarify IMU data. Use of wearable video-based cameras would provide a comprehensive understanding of an individual’s habitual fall risk, adding context to clarify abnormal IMU data. Generally, there is taboo when suggesting the use of wearable cameras to capture real-world video, clinical and patient apprehension due to ethical and privacy concerns. This perspective proposes that routine use of wearable cameras could be realized within digital medicine through AI-based computer vision models to obfuscate/blur/shade sensitive information while preserving helpful contextual information for a comprehensive patient assessment. Specifically, no person sees the raw video data to understand context, rather AI interprets the raw video data first to blur sensitive objects and uphold privacy. That may be more routinely achieved than one imagines as contemporary resources exist. Here, to showcase/display the potential an exemplar model is suggested via off-the-shelf methods to detect and blur sensitive objects (e.g., people) with an accuracy of 88%. Here, the benefit of the proposed approach includes a more comprehensive understanding of an individual’s free-living fall risk (from free-living IMU-based gait) without compromising privacy. More generally, the video and AI approach could be used beyond fall risk to better inform habitual experiences and challenges across a range of clinical cohorts. Medicine is becoming more receptive to wearables as a helpful toolbox, camera-based devices should be plausible instruments.
The effect of omentoplasty in various surgical operations: systematic review and meta-analysis
Authors: Yaqi Peng, Shan Xiong, Yujin Ding, Limin Xie, Yihang Wang, Ying Mei, Wei Liu, Tuo Deng
Journal: International Journal of Surgery (2024)

Omentoplasty is commonly used in various surgeries. However, its effectiveness is unsure due to lack of convincing data and research. To clarify the impact of omentoplasty on postoperative complications of various procedures, this systematic review and meta-analysis was performed.
Emergency trauma care: Pakistan’s preparedness amidst the growing impact of rapid climate change
Authors: Ayesha Muhammad, Areej Z. Qureshi, Muhammad Farhan, Malik Olatunde Oduoye, Faizan Shehzad, Muhammad Imran
Journal: International Journal of Surgery (2024)

Muhammad, Ayesha; Qureshi, Areej Z.; Farhan, Muhammad; Oduoye, Malik O.; Shehzad, Faizan; Imran, Muhammad Author Information
A commentary on can ChatGPT assist urologists manage overactive bladder?
Authors: Changkun Mao, Tao Zhang
Journal: International Journal of Surgery (2024)

Department of Urology, Anhui Provincial Children's Hospital, Hefei,230022,Anhui, China 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 Urology, Anhui Provincial Children's Hospital, Hefei, 230022, Anhui, China. E-mail address: [email protected] (C.-K. Mao). 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/
C-reactive protein/lymphocyte ratio as a prognostic biomarker in acute pancreatitis: a cross-sectional study assessing disease severity
Authors: Xinqi Chen, Zhijin Lin, Yani Chen, Chanchan Lin
Journal: International Journal of Surgery (2024)

Background: The C-reactive protein/lymphocyte ratio (CLR) is a prognostic biomarker of various diseases. However, its significance in acute pancreatitis (AP) remains unknown. The main aim of this study was to investigate the association between the CLR and disease severity in patients with AP. Methods: This cross-sectional study included 476 AP patients (mild acute pancreatitis (MAP), n =176; moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), n=300). The primary exposure of interest was the baseline CLR. The primary outcome was the incidence of moderate to severe AP. Multivariate logistic regression and restricted cubic spline analyses were performed to evaluate the association between the CLR and the incidence of moderate to severe AP. Receiver operating characteristic (ROC) analysis was conducted to assess the predictive efficacy, sensitivity, and specificity of CLR in predicting the incidence of moderate to severe AP. Results: The mean age of the patients was 44±13.2 years, and 76.5% were male. The distribution of CLR was 31.6 (interquartile range, 4.5, 101.7). Moderate to severe AP occurred in 300 cases (63.0%). After multiple adjustments, CLR was independently associated with the incidence of moderate to severe AP (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03, 1.05; P &lt; 0.001). A nonlinear relationship was found between CLR and the incidence of moderate to severe AP, with a threshold of approximately 45. The effect size and CI below and above the threshold value were 1.061 (1.033–1.089) and 1.014 (0.997–1.031), respectively. The area under the curve (AUC) for CLR was 87.577% (95% CI: 84.443% ~ 90.710%) with an optimal cut-off value of 30.835, resulting in a sensitivity of 73.7% and a specificity of 88.6%. Conclusions: There was a nonlinear relationship with a saturation effect between the CLR and the incidence of moderate to severe AP. The CLR measured within 24 h of admission may serve as a promising biomarker for predicting the emergence of moderate to severe AP, thereby providing a more scientifically grounded basis for preventing such cases. Nonetheless, further research is warranted to validate and strengthen these findings.
Impact of preoperative virtual reality education on surgical patients: additional considerations
Authors: Zhi-Qing Zhan, Zhangkai J. Cheng
Journal: International Journal of Surgery (2024)

aDepartment of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China bDivision of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Guangzhou Medical University CHINA. E-mail address: [email protected] (Z.J. Cheng). 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/
Revolutionizing oral and maxillofacial surgery: ChatGPT’s impact on decision support, patient communication, and continuing education
Authors: Mohmed Isaqali Karobari, Hema Suryawanshi, Santosh R. Patil
Journal: International Journal of Surgery (2024)

Karobari, Mohmed Isaqali BDS, MSC (Endo), MFDS. RCPS(Galsg), [PhD Scholar]; Suryawanshi, Hema; Patil, Santosh R. Author Information
A commentary on ‘Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study’
Authors: Xin Zhao, Fengwei Gao, Zehua Lei
Journal: International Journal of Surgery (2024)

aDepartment of Hepato-Pancreato-biliary Surgery,People's Hospital of Leshan, Leshan, 614000, China bLiver Transplantation Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: People's Hospital of Leshan, No. 238, Baita street, Shizhong District, Leshan, Sichuan Province, China. E-mail address: [email protected] (Z. Lei). 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/
Practice for the treatment of noncontiguous double-level lumbar spinal stenosis with degenerative spondylolisthesis and scoliosis with Endo-LIF
Authors: Changjun Chen, Qingwei Ma, Lei Zhang
Journal: International Journal of Surgery (2024)

Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China 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 Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China. Tel: +86 053189269860. E-mail address: [email protected] (C. Chen). *Corresponding author. Address: Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China. Tel: +86 053189269860. E-mail address: [email protected] (L. Zhang). 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/
Management for degenerative lumbar spondylolisthesis: a network meta-analysis and systematic review basing on randomized controlled trials
Authors: Hao Jia, Zhuo Zhang, Jianpu Qin, Lipei Bao, Jun Ao, Hu Qian
Journal: International Journal of Surgery (2024)

Background: Consensus on the various interventions for degenerative lumbar spondylolisthesis (DLS) remains unclear. Materials and methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and major scientific websites until Nov 01, 2023, to screen eligible randomized controlled trials (RCTs) involving the treatment of DLS. The seven most common DLS interventions (non-surgical [NS], decompression only [DO], decompression plus fusion without internal fixation [DF], decompression plus fusion with internal fixation [DFI], endoscopic decompression plus fusion [EDF], endoscopic decompression [ED], and circumferential fusion [360F]) were compared. The primary (pain and disability) and secondary (complications, reoperation rate, operation time, blood loss, length of hospital stay, and satisfaction) outcomes were analyzed. Results: Data involving 3,273 patients in 16 RCTs comparing the efficacy of different interventions for DLS were reported. In terms of improving patient pain and dysfunction, there was a significant difference between surgical and NS. EDF showed the greatest improvement in short-term and long-term dysfunction (probability, 7.1% and 21.0%). Moreover, EDF had a higher complication rate (probability 70.8%), lower reoperation rate (probability, 20.2%), and caused greater blood loss (probability, 82.5%) than other surgical interventions. Endoscopic surgery had the shortest hospitalization time (EDF: probability, 42.6%; ED: probability, 3.9%). DF and DFI had the highest satisfaction scores. Conclusions: Despite the high complication rate of EDF, its advantages include improvement in pain, lower reoperation rate, and shorter hospitalization duration. Therefore, EDF may be a good option for patients with DLS as a less invasive surgical approach.
Anatomic and Functional Discordance Among Patients With Nonobstructive Coronary Disease
Authors: Jennifer A. Rymer, Nicholas Ng, Hidenobu Takagi, Lynne M. Koweek, Pamela S. Douglas, Bernard De Bruyne, Bjarne L. Norgaard, Manesh R. Patel, Jonathon A. Leipsic, Melissa A. Daubert
Journal: JACC. Cardiovascular imaging (2024)
Author Correction: Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial
Authors: Yara L Verschoor, Joris van de Haar, José G van den Berg, Johanna W van Sandick, Liudmila L Kodach, Jolanda M van Dieren, Sara Balduzzi, Cecile Grootscholten, Marieke E IJsselsteijn, Alexander A F A Veenhof, Koen J Hartemink, Marieke A Vollebergh, Adham Jurdi, Shruti Sharma, Erik Spickard, Emilia C Owers, Annemarieke Bartels-Rutten, Peggy den Hartog, Noel F C C de Miranda, Monique E van Leerdam, John B A G Haanen, Ton N Schumacher, Emile E Voest, Myriam Chalabi
Journal: Nature Medicine (2024)
Sex differences in kidney metabolism may reflect sex-dependent outcomes in human diabetic kidney disease
Authors: Sergi Clotet-Freixas, Olga Zaslaver, Max Kotlyar, Chiara Pastrello, Andrew T. Quaile, Caitriona M. McEvoy, Aninda D. Saha, Sofia Farkona, Alex Boshart, Katarina Zorcic, Slaghaniya Neupane, Kieran Manion, Maya Allen, Michael Chan, Xuqi Chen, Arthur P. Arnold, Peggy Sekula, Inga Steinbrenner, Anna Köttgen, Allison B. Dart, Brandy Wicklow, Jon M. McGavock, Tom D. Blydt-Hansen, Clara Barrios, Marta Riera, María J. Soler, Amandine Isenbrandt, Jérôme Lamontagne-Proulx, Solène Pradeloux, Katherine Coulombe, Denis Soulet, Shravanthi Rajasekar, Boyang Zhang, Rohan John, Aman Mehrotra, Adam Gehring, Maija Puhka, Igor Jurisica, Minna Woo, James W. Scholey, Hannes Röst, Ana Konvalinka
Journal: Science Translational Medicine (2024)

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) and progresses faster in males than in females. We identify sex-based differences in kidney metabolism and in the blood metabolome of male and female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy males displayed increased mitochondrial respiration, oxidative stress, apoptosis, and greater injury when exposed to high glucose compared with PTECs from healthy females. Male human PTECs showed increased glucose and glutamine fluxes to the TCA cycle, whereas female human PTECs showed increased pyruvate content. The male human PTEC phenotype was enhanced by dihydrotestosterone and mediated by the transcription factor HNF4A and histone demethylase KDM6A. In mice where sex chromosomes either matched or did not match gonadal sex, male gonadal sex contributed to the kidney metabolism differences between males and females. A blood metabolomics analysis in a cohort of adolescents with or without diabetes showed increased TCA cycle metabolites in males. In a second cohort of adults with diabetes, females without DKD had higher serum pyruvate concentrations than did males with or without DKD. Serum pyruvate concentrations positively correlated with the estimated glomerular filtration rate, a measure of kidney function, and negatively correlated with all-cause mortality in this cohort. In a third cohort of adults with CKD, male sex and diabetes were associated with increased plasma TCA cycle metabolites, which correlated with all-cause mortality. These findings suggest that differences in male and female kidney metabolism may contribute to sex-dependent outcomes in DKD.
Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice
Authors: Qiuhua Yang, Yongfeng Cai, Qian Ma, Albert Xiong, Peishan Xu, Zhidan Zhang, Jiean Xu, Yaqi Zhou, Zhiping Liu, Dingwei Zhao, John Asara, Wei Li, Huidong Shi, Ruth B. Caldwell, Akrit Sodhi, Yuqing Huo
Journal: Science Translational Medicine (2024)

Anti–vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A ( Adora2a ), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury–induced CNV or mice with a deficiency in the very low–density lipoprotein receptor), we found that deletion of Adora2a either globally or specifically in endothelial cells reduced subretinal fibrosis independently of angiogenesis. We showed that Adora2a -dependent endothelial-to-mesenchymal transition contributed to the development of subretinal fibrosis in mice with laser injury–induced CNV. Deficiency of Adora2a in cultured mouse and human choroidal endothelial cells suppressed induction of the endothelial-to-mesenchymal transition. A metabolomics analysis of cultured human choroidal endothelial cells showed that ADORA2A knockdown with an siRNA reversed the increase in succinate because of decreased succinate dehydrogenase B expression under fibrotic conditions. Pharmacological inhibition of ADORA2A with a small-molecule KW6002 in both mouse models recapitulated the reduction in subretinal fibrosis observed in mice with genetic deletion of Adora2a . ADORA2A inhibition may be a therapeutic approach to treat subretinal fibrosis associated with nAMD.