tbuckley/cabot-search huggingface dataset:
Combined endoscopic submucosal dissection and endoscopic laryngopharyngeal surgery for an oropharyngeal lesion extending to the flap of a glossopharyngeal reconstruction
Authors: Kotaro Waki, Kenshi Matsuno, Hideaki Miyamoto, Ryosuke Gushima, Daizo Murakami, Yorihisa Orita, Yasuhito Tanaka
Journal: Endoscopy (2024)

Pharyngeal endoscopic submucosal dissection (ESD) [1] and endoscopic laryngopharyngeal surgery (ELPS) [2] [3] are reportedly effective treatments for superficial pharyngeal cancer (SPC). ESD allows the clinician to perform highly precise procedures involving large treatable areas owing to endoscopic manipulation. Although the treatable area of ELPS is limited by the mobility of the transoral devices, the operator can independently control the traction during dissection, resulting in efficient procedures [3]. Considering these characteristics, we present a case of SPC extending to the reconstructed flap that was resected using a combined ESD and ELPS procedure.
Cholecystohepaticogastrostomy: novel endoscopic gallbladder drainage technique to prevent acute cholecystitis following endoscopic ultrasound-guided biliary drainage
Authors: Juan Alfonso Maclang Mendoza, Yu-Ting Kuo, Chen-Ling Peng, Hsiu-Po Wang
Journal: Endoscopy (2024)

For malignant distal biliary obstruction (DBO), placing a stent in an antegrade manner across the obstruction and papilla, followed by endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), establishes dual biliary drainage pathways and may prolong stent patency [1]. However, acute cholecystitis can occur after biliary drainage with a fully covered self-expandable metal stent (FCSEMS) in cases of DBO [2]. We present a novel endoscopic approach for gallbladder drainage via the HGS tract, offering a viable option for high-risk patients who develop acute cholecystitis following FCSEMS placement.
Modified NOTES technique for creation of an endoscopic gastrojejunostomy
Authors: Natalie J. Wilson, Rahul Karna, Mohammad Bilal
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) with a lumen-apposing metal stent (LAMS) relies on endosonographic visualization of the jejunum. In cases where jejunal visualization is not possible, natural orifice transluminal endoscopic surgery (NOTES) can offer an alternative technique for performing endoscopic gastrojejunostomy (EGJ).
Assessment methods for senior resident attainment based on a new training model
Authors: Hiroki Kato, Makoto Kobayashi, Hirotaka Takeshima, Hiroshi Nakayabu, Akihiro Maruyama, Shintaro Tominaga, Hitoshi Sugiyama
Journal: Endoscopy (2024)

We previously reported on the use of the Endoscopist & Assistant's Simulator dry lab (EASY; Tanac Co. Ltd., Gifu, Japan) for recruiting junior residents and training senior residents in cold snare polypectomy (CSP) [1] [2] ([Fig. 1]). This study examined the time required for CSP training to assess senior residents' achievement levels.
Reverse cannulation and dilation successfully assist the cannulation of the accessory pancreatic duct
Authors: Yi-Li Cai, Fan Wang, Miao Liu, Ting Yang, Zhao-Shen Li, Liang-Hao Hu
Journal: Endoscopy (2024)

A 68-year-old woman with chronic pancreatitis and pancreatic duct stones was admitted to hospital due to recurrent abdominal pain. Extracorporeal shock wave lithotripsy was performed before endoscopic retrograde cholangiopancreatography (ERCP). Pancreatogram revealed that the main pancreatic duct (MPD) was twisted and formed an α loop structure, which made stent placement impossible ([Fig. 1]). In this case, the accessory pancreatic duct (APD) assumed the drainage function.
Endoluminal single-clip traction-assisted endoscopic submucosal dissection: a green tip to reduce waste and cost
Authors: Zeyu Wu, Yonggang Ding, Qide Zhang
Journal: Endoscopy (2024)

A 66-year-old man was referred to our hospital for endoscopic submucosal dissection (ESD) of a descending colonic laterally spreading tumor with pit pattern type IIIL and IVV ([Fig. 1]). The lesion was located on the lower side with respect to gravity when the patient underwent endoscopic operation in the left lateral position. We designed an endoluminal single-clip traction (ECT) method to assist ESD.
Over-the-scope pre-looping method using an endoloop in endoscopic full-thickness resection of gastric gastrointestinal stromal tumor
Authors: Reona Kawamura, Seiichiro Abe, Yasuhiko Mizuguchi, Satoru Nonaka, Yutaka Saito
Journal: Endoscopy (2024)

Endoscopic full-thickness resection (EFTR) for small gastric gastrointestinal stromal tumors (GISTs) is a feasible and effective procedure [1]. However, visual field obstruction during defect approximation post-EFTR often poses a challenge due to inadequate gastric distension [2].
Cerebral endothelial 3-mercaptopyruvate sulfurtransferase improves ischemia-induced cognitive impairment via interacting with protein phosphatase 2A
Authors: Li Zhu, Yi Huang, Jing Jin, Rongjun Zou, Rui Zuo, Yong Luo, Ziqing Song, Linfeng Dai, Minyi Zhang, Qiuhe Chen, Yunting Wang, Wei Wang, Rongrong He, Yang Chen
Journal: Acta Pharmaceutica Sinica B (2024)

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H2S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H2S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2AEC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H2S signaling pathway. A robust reduction in endothelial MPST-dependent H2S production followed PP2A deficiency. Exogenous H2S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2AEC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H2S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.
YOD1 regulates microglial homeostasis by deubiquitinating MYH9 to promote the pathogenesis of Alzheimer’s disease
Authors: Jinfeng Sun, Fan Chen, Lingyu She, Yuqing Zeng, Hao Tang, Bozhi Ye, Wenhua Zheng, Li Xiong, Liwei Li, Luyao Li, Qin Yu, Linjie Chen, Wei Wang, Guang Liang, Xia Zhao
Journal: Acta Pharmaceutica Sinica B (2024)

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.
The PGAM5–NEK7 interaction is a therapeutic target for NLRP3 inflammasome activation in colitis
Authors: Cheng-Long Gao, Jinqian Song, Haojie Wang, Qinghong Shang, Xin Guan, Gang Xu, Jiayang Wu, Dalei Wu, Yueqin Zheng, Xudong Wu, Feng Zhao, Xindong Liu, Lei Shi, Tao Pang
Journal: Acta Pharmaceutica Sinica B (2024)

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.
Osteosarcopenic adiposity and its relation to cancer and chronic diseases: Implications for research to delineate mechanisms and improve clinical outcomes
Authors: Jasminka Z Ilich, Biljana Pokimica, Danijela Ristić-Medić, Snjezana Petrović, Aleksandra Arsić, Nadja Vasiljević, Vesna Vučić, Owen J Kelly
Journal: Ageing Research Reviews (2024)
Safety, pharmacokinetics, and early bactericidal activity of quabodepistat in combination with delamanid, bedaquiline, or both in adults with pulmonary tuberculosis: a randomised, active-controlled, open-label trial
Authors: Rodney Dawson, Andreas H Diacon, Veronique De Jager, Kim Narunsky, V Mischka Moodley, Kelly W Stinson, Yongge Liu, Bo Zheng, Jeffrey Hafkin
Journal: The Lancet Infectious Diseases (2024)
Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cells
Authors: Han Liu, Yujie Hong, Hui Chen, Xianggui Wang, Jiale Dong, Xiaoqian Li, Zihan Shi, Qian Zhao, Longyuan Zhou, JiaXin Wang, Qiuling Zeng, Qinglin Tang, Qi Liu, Florian Rieder, Baili Chen, Minhu Chen, Rui Wang, Yao Zhang, Ren Mao, Xianxing Jiang
Journal: Acta Pharmaceutica Sinica B (2024)

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.
Sequential activation of osteogenic microenvironment via composite peptide-modified microfluidic microspheres for promoting bone regeneration
Authors: Liang Wu, Tao Xu, Sen Li, Kai Sun, Ziyang Tang, Hui Xu, Yong Qiu, Zhenhua Feng, Zhen Liu, Zezhang Zhu, Xiaodong Qin
Journal: Biomaterials (2024)
A Primer on Reinforcement Learning in Medicine for Clinicians
Authors: Pushkala Jayaraman, Jacob Desman, Moein Sabounchi, Girish N. Nadkarni, Ankit Sakhuja
Journal: npj Digital Medicine (2024)

Reinforcement Learning (RL) is a machine learning paradigm that enhances clinical decision-making for healthcare professionals by addressing uncertainties and optimizing sequential treatment strategies. RL leverages patient-data to create personalized treatment plans, improving outcomes and resource efficiency. This review introduces RL to a clinical audience, exploring core concepts, potential applications, and challenges in integrating RL into clinical practice, offering insights into efficient, personalized, and effective patient care.
De-escalated neoadjuvant weekly nab-paclitaxel with trastuzumab and pertuzumab versus docetaxel, carboplatin, trastuzumab, and pertuzumab in patients with HER2-positive early breast cancer (HELEN-006): a multicentre, randomised, phase 3 trial
Authors: Xiu-Chun Chen, De-Chuang Jiao, Jiang-Hua Qiao, Cheng-Zheng Wang, Xian-Fu Sun, Zhen-Duo Lu, Lian-Fang Li, Chong-Jian Zhang, Min Yan, Ya Wei, Bo Chen, Yue-Qing Feng, Miao Deng, Ming-De Ma, Jennifer K Plichta, You-Wen He, Zhen-Zhen Liu
Journal: The Lancet Oncology (2024)
A novel CD71 Centyrin:Gys1 siRNA targeting and delivery platform reduces glycogen synthesis and glycogen levels in a mouse model of Pompe disease
Authors: Bryce D Holt, Samuel J Elliott, Rebecca Meyer, Daniela Reyes, Karyn O'Neil, Zhanna Druzina, Swapnil Kulkarni, Beth L Thurberg, Steven G Nadler, Bartholomew A Pederson
Journal: Molecular Therapy (2024)

Pompe disease is caused by acid alpha-glucosidase (GAA) deficiency, resulting in lysosomal glycogen accumulation. This disease is characterized by progressive skeletal muscle weakness, respiratory distress, and in the infantile-onset form, cardiomyopathy. The only approved treatment is enzyme replacement therapy (ERT) with human recombinant GAA. While ERT therapy extends life span, residual symptoms remain, with poor muscle uptake and immunogenicity limiting efficacy. We examined a novel Centyrin protein-short interfering ribonucleic acid (siRNA) conjugate targeting CD71 (transferrin receptor type 1, TfR1) and GYS1, a key enzyme involved in glycogen synthesis. Unlike existing ERTs designed to degrade aberrant glycogen deposits observed in Pompe patients, the CD71 Centyrin:Gys1 siRNA is designed to restore glycogen balance by inhibiting glycogen synthesis. To this end, we administered the CD71 Centyrin:Gys1 siRNA conjugate to the 6
Expanded immune imprinting and neutralization spectrum by hybrid immunization following breakthrough infections with SARS-CoV-2 variants after three-dose vaccination
Authors: Tingting Jia, Fuxiang Wang, Yihao Chen, Guancheng Liao, Qiuyi Xu, Jiamin Chen, Jiani Wu, Nina Li, Liangliang Wang, Lifang Yuan, Dongli Wang, Qian Xie, Chuming Luo, Huanle Luo, Yanqun Wang, Yongkun Chen, Yuelong Shu
Journal: Journal of Infection (2024)
p38α–eIF6–Nsun2 axis promotes ILC3’s rapid response to protect host from intestinal inflammation
Authors: Jida Huang, Jing Zhang, Panwei Song, Jiaoyan Huang, Zi Yang, Jiahuai Han, Li Wu, Xiaohuan Guo
Journal: The Journal of Experimental Medicine (2024)

Group 3 innate lymphoid cells (ILC3s) are important for maintaining gut homeostasis. Upon stimulation, ILC3s can rapidly produce cytokines to protect against infections and colitis. However, the regulation of ILC3 quick response is still unclear. Here, we find that eIF6 aggregates with Nsun2 and cytokine mRNA in ILC3s at steady state, which inhibits the methyltransferase activity of Nsun2 and the nuclear export of cytokine mRNA, resulting in the nuclear reservation of cytokine mRNA. Upon stimulation, phosphorylated p38α phosphorylates eIF6, which in turn releases Nsun2 activity, and promotes the nuclear export of cytokine mRNA and rapid cytokine production. Genetic disruption of p38α, Nsun2, or eIF6 in ILC3s influences the mRNA nuclear export and protein expression of the protective cytokines, thus leading to increased susceptibility to colitis. Together, our data identify a crucial role of the p38α–eIF6–Nsun2 axis in regulating rapid ILC3 immune response at the posttranscriptional level, which is critical for gut homeostasis maintenance and protection against gut inflammation.
Randomized Controlled Trial of a Virtually Delivered Exercise and Stress Management Program to Improve Physical Performance of Hematopoietic Cell Transplant Survivors
Authors: David D. Ma, Zhixin Liu, Kimberley Au, Mei Tran, Crisbel M. Artuz, Matthew Greenwood, Ian Bilmon, David Kliman
Journal: Journal of Clinical Oncology (2024)

Because of advances in hematopoietic cell transplant (HCT), meeting the long-term health needs of increasing numbers of HCT survivors remains challenging. This multicenter trial aimed to assess the short- and long-term effects of an exercise and mindfulness intervention delivered by telehealth. One hundred thirty-nine participants >6 months post-HCT were randomly assigned 1:1 to a 6-week personalized exercise and mindfulness training with three motivation sessions at 3-6 months via an online meeting platform or usual care. Physical and quality-of-life (QOL) assessments were conducted online for 12 months. The primary end point was the 6-minute walk test (6-MWT) at 3 months. The median time post-HCT was 21 months (range, 7-67 months). Improvement in mean difference of 6-MWT was found in the intervention group compared with control (intention-to-treat) at 3 months (51.4 m [95% CI, 27.3 to 75.5]; P < .001; effect size [ES], 0.52) and was maintained at 12 months (59.3 m, P = .003; ES, 0.60). Sustained improvements in mean difference for sit-to-stand (STS) at 3 and 12 months were seen. There were no significant changes in hand grip strength or QOL outcomes between groups. A significant difference in serum soluble intercellular adhesion molecule-1 (sICAM-1) concentration was observed between the intervention and control groups in the exploratory study. No intervention adverse events were found. The supervised multimodal telehealth intervention provided clinically meaningful and durable improvement of physical capacity in HCT survivors. This home-based program has the potential to provide an unmet need for HCT survivors. Similar programs may benefit survivors of other cancers, organ transplants, and chronic disorders.
COP29: Deal to raise $300bn a year by 2035 for poorer countries is hailed and slated
Authors: Dominic Murphy
Journal: BMJ (2024)

Baku's COP29 climate talks ended on 24 November with a finance deal that fell far short of some countries' expectations, while others hailed it as a success.After two weeks of intense-and often fraught-negotiations in the Azerbaijani capital, developed nations have agreed to raise at least $300bn (£238bn; €286bn) a year for low and middle income countries by 2035.This is to help them phase out fossil fuels and adapt to climate change.1 Club of Rome.Open letter on COP reform to all states that are parties to the convention.15 November
Role of age and exposure duration in the association between metabolic syndrome and risk of incident dementia: a prospective cohort study
Authors: Danial Qureshi, Robert Luben, Shabina Hayat, Robert Talarico, Naomi E Allen, Elżbieta Kuźma, Thomas J Littlejohns
Journal: The Lancet Healthy Longevity (2024)

Metabolic syndrome could be a modifiable risk factor for dementia. However, the effects of age and duration of exposure to metabolic syndrome on dementia risk remains underexplored. The aim of this study was to determine whether the association between metabolic syndrome and risk of dementia differs across mid-life versus late-life, and to explore how duration of metabolic syndrome affects this risk. We conducted a population-based prospective study using data from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort. Metabolic syndrome was defined as having at least three of the following: elevated waist circumference, triglycerides, blood pressure, or glycated haemoglobin, or reduced HDL cholesterol. Incident all-cause dementia was ascertained through hospital inpatient, death, and mental health-care records. In full-cohort analyses, we studied 20 150 adults without dementia aged 50-79 years who attended baseline assessments. Cox proportional hazards models were used to estimate the association between metabolic syndrome and dementia in the full sample, and in mid-life (50-59 years and 60-69 years) and late-life (70-79 years). To assess duration of metabolic syndrome, group-based trajectory analysis was performed on 12 756 participants who attended at least two health assessments over 20 years. The mean age of participants was 62·6 years (SD 7·5), and 10 857 (54%) were female. Over 25 years of follow-up (mean 18·8 years [SD 6·3]), 2653 (13%) participants developed dementia. In the full cohort, metabolic syndrome was associated with an increased risk of dementia (hazard ratio 1·11, 95% CI 1·01-1·21). In age-specific analyses, the association was similar for participants in late mid-life (age 60-69 years: 1·21, 1·05-1·39) and, although non-significant, in early mid-life (age 50-59 years: 1·12, 0·87-1·43), but attenuated for participants in late-life (age 70-79 years: 0·96, 0·81-1·14). A linear trend was observed between the number of metabolic syndrome components and dementia risk in those aged 60-69 years (ptrend=0·0040), but not in other age groups. In trajectory analysis, a prolonged duration of metabolic syndrome was associated with a significantly increased risk of developing dementia (1·26, 1·13-1·40) when compared to those with consistently low metabolic syndrome. No association was found for increasing metabolic syndrome (1·01, 0·88-1·17). These findings provide insights into how certain age windows and time periods might differentially affect dementia risk in the context of metabolic syndrome, and highlight the importance of considering age and duration of exposure to metabolic syndrome when devising dementia prevention strategies. Canadian Institutes of Health Research-Institute of Aging, Oxford Population Health, and the Nicolaus and Margrit Langbehn Foundation.
Safety and immunogenicity of the ChAdOx1–MVA-vectored conserved mosaic HIVconsvX candidate T-cell vaccines in HIV-CORE 005.2, an open-label, dose-escalation, first-in-human, phase 1 trial in adults living without HIV-1 in the UK
Authors: Nicola Borthwick, Natalia Fernandez, Peter J Hayes, Edmund G-T Wee, Belkis M Akis Yildirim, Andrea Baines, Megan Baker, Nicholas Byard, Oliver Conway, Molly Glaze, Daniel Jenkin, Colin Larkworthy, Michael Luciw, Abigail Platt, Ian Poulton, Merin Thomas, Jack Quaddy, Marion Watson, Alison Crook, Paola Cicconi, Tomáš Hanke
Journal: The Lancet Microbe (2024)
Are digital psychological interventions for psychological distress and quality of life in cancer patients effective? A systematic review and network meta-analysis
Authors: Tao Zhang, Zhihong Ren, Claire Elizabeth Wakefield, Bryant Pui Hung Hui, Tatsuo Akechi, Congrong Shi, Xiayu Du, Wenke Chen, Lizu Lai, Chunxiao Zhao, Ying Li, Yubu Zhou
Journal: Clinical Psychology Review (2024)