tbuckley/cabot-search huggingface dataset:
Depression Onset After a Spouse’s Cardiovascular Event
Authors: Toshiaki Komura, Yusuke Tsugawa, Naoki Kondo, Kosuke Inoue
Journal: JAMA Network Open (2024)

Importance Although cardiovascular disease (CVD) is a known risk factor for depression, evidence is lacking regarding whether and to what extent a spouse’s CVD is associated with the subsequent mental health of individuals. Objective To examine the association between CVD onset in spouses and subsequent depression. Design, Setting, and Participants This cohort study examined 277 142 matched married couples enrolled in the Japan Health Insurance Association health insurance program between April 2015 and March 2022, covering approximately 40% of the working-age population in Japan. Index individuals (primary insured) whose spouses (dependent) experienced incident CVD between April 2016 and March 2022 were 1:1 matched to controls whose spouses did not experience CVD. Matching was based on age, sex, income, or the onset date of the spouses’ CVD. Data analysis was conducted from April 2016 to March 2022. Exposure Spousal onset of CVD between fiscal years 2016 and 2021. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes were used to identify the composite CVD outcomes (stroke, heart failure, and myocardial infarction). Main Outcomes and Measures Multivariate Cox proportional hazards models were used to investigate the association between spouses’ new-onset CVD and individuals’ depression, adjusting for sociodemographic characteristics and comorbidities of index individuals (diabetes, hypertension, and CVD) and spouses (diabetes, hypertension, and depression). Subgroup analyses were conducted according to sex, age, income levels, and history of CVD. Results Among 277 142 matched pairs of married couples, 263 610 (95.1%) had a male index individual; the mean (SD) age of index individuals was 58.2 (10.2) years. A new onset of depression was observed in 4876 individuals (1.8%). In multivariable Cox models, there was an association between the spouse’s CVD and the individuals’ depression (hazard ratio, 1.13 [95% CI, 1.07-1.20]). The subgroup analysis found no evidence of heterogeneity in sex, age, income level, or CVD history. The results were consistent when additionally adjusted for health behaviors (smoking, alcohol consumption, physical activity, and use of antihypertensive drugs) and objectively measured physical health conditions (body mass index, blood pressure, cholesterol levels, glucose levels, and estimated glomerular filtration rate) (hazard ratio, 1.16 [95% CI, 1.06-1.28]). Conclusions and Relevance In this nationwide cohort study of matched couples, a spouse’s onset of CVD was associated with an increased risk of an individual’s depression. These findings highlight the importance of preventive care for mental health disorders in individuals whose spouses experience incident CVD.
Self-regulating CAR-T cells modulate cytokine release syndrome in adoptive T-cell therapy
Authors: Meng-Yin Lin, Eunwoo Nam, Ryan M. Shih, Amanda Shafer, Amber Bouren, Melanie Ayala Ceja, Caitlin Harris, Mobina Khericha, Kenny H. Vo, Minsoo Kim, Chi-Hong Tseng, Yvonne Y. Chen
Journal: The Journal of Experimental Medicine (2024)

Cytokine release syndrome (CRS) is a frequently observed side effect of chimeric antigen receptor (CAR)-T cell therapy. Here, we report self-regulating T cells that reduce CRS severity by secreting inhibitors of cytokines associated with CRS. With a humanized NSG-SGM3 mouse model, we show reduced CRS-related toxicity in mice treated with CAR-T cells secreting tocilizumab-derived single-chain variable fragment (Toci), yielding a safety profile superior to that of single-dose systemic tocilizumab administration. Unexpectedly, Toci-secreting CD19 CAR-T cells exhibit superior in vivo antitumor efficacy compared with conventional CD19 CAR-T cells. scRNA-seq analysis of immune cells recovered from tumor-bearing humanized mice revealed treatment with Toci-secreting CD19 CAR-T cells enriches for cytotoxic T cells while retaining memory T-cell phenotype, suggesting Toci secretion not only reduces toxicity but also significantly alters the overall T-cell composition. This approach of engineering T cells to self-regulate inflammatory cytokine production is a clinically compatible strategy with the potential to simultaneously enhance safety and efficacy of CAR-T cell therapy for cancer.
Remotely controlled drug release in deep brain regions of non-human primates
Authors: Matthew G. Wilson, Taylor D. Webb, Henrik Odéen, Jan Kubanek
Journal: Journal of Controlled Release (2024)

Many areas of science and medicine would benefit from selective release of drugs in specific regions. Nanoparticle drug carriers activated by focused ultrasound—remotely applied, depth-penetrating energy—may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects' visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MR imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior.
Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the <scp>ESC</scp>
Authors: Wilfried Mullens, Kevin Damman, Sebastiaan Dhont, Debasish Banerjee, Antoni Bayes‐Genis, Antonio Cannata, Ovidiu Chioncel, Maja Cikes, Justin Ezekowitz, Andreas J. Flammer, Pieter Martens, Alexandre Mebazaa, Robert J. Mentz, Òscar Miró, Brenda Moura, Julio Nunez, Jozine M. Ter Maaten, Jeffrey Testani, Roland van Kimmenade, Frederik H. Verbrugge, Marco Metra, Giuseppe M.C. Rosano, Gerasimos Filippatos
Journal: European Journal of Heart Failure (2024)
Immune drivers of physiological and pathological pain
Authors: Aakanksha Jain, Sara Hakim, Clifford J. Woolf
Journal: The Journal of Experimental Medicine (2024)

Physiological pain serves as a warning of exposure to danger and prompts us to withdraw from noxious stimuli to prevent tissue damage. Pain can also alert us of an infection or organ dysfunction and aids in locating such malfunction. However, there are instances where pain is purely pathological, such as unresolved pain following an inflammation or injury to the nervous system, and this can be debilitating and persistent. We now appreciate that immune cells are integral to both physiological and pathological pain, and that pain, in consequence, is not strictly a neuronal phenomenon. Here, we discuss recent findings on how immune cells in the skin, nerve, dorsal root ganglia, and spinal cord interact with somatosensory neurons to mediate pain. We also discuss how both innate and adaptive immune cells, by releasing various ligands and mediators, contribute to the initiation, modulation, persistence, or resolution of various modalities of pain. Finally, we propose that the neuroimmune axis is an attractive target for pain treatment, but the challenges in objectively quantifying pain preclinically, variable sex differences in pain presentation, as well as adverse outcomes associated with immune system modulation, all need to be considered in the development of immunotherapies against pain.
Hybrid biomineralized nanovesicles to enhance inflamed lung biodistribution and reduce side effect of glucocorticoid for ARDS therapy
Authors: Qi Qiao, Xiaonan Li, Xiangjun Ou, Xiong Liu, Chuansheng Fu, Yi Wang, Boning Niu, Li Kong, Conglian Yang, Zhiping Zhang
Journal: Journal of Controlled Release (2024)
B cell pathway dual inhibition for systemic lupus erythematosus: a prospective single‐arm cohort study of telitacicept
Authors: Lanlan Ji, Yan Geng, Xiaohui Zhang, Xuerong Deng, Zhibo Song, Meng Tan, Ying Tan, Chenxue Qu, Zhuoli Zhang
Journal: MedComm (2024)

Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with B‐cell hyperactivity. Telitacicept is a transmembrane activator, calcium modulator, and cyclophilin ligand interactor‐Fc fusion protein, which can neutralize both B‐cell lymphocyte stimulator and a proliferation‐inducing ligand. Patients with active SLE who received telitacicept were prospectively followed at month 1, 3, 6, 9, and 12 after telitacicept initiation. Thirty‐seven participants were involved and followed for 6.00 [3.00, 6.00] months. SRI‐4 rate at month 6 was 44.7%. The median dosage of prednisone was decreased by 43.8% (from 10 to 5.62 mg/d) at month 6. The anti‐dsDNA level was significantly decreased, while complement levels were significantly increased at month 6 from baseline. Continuously significant reductions in serum immunoglobin (Ig)G IgA, and IgM levels were also observed. Patients experienced significant decreases in the numbers of total and naive B cells, whereas memory B cells and T cell populations did not change. The number of NK cells was significantly increased during the follow‐up. At month 6, 58.3% (14 out of 24) patients experienced improved fatigue accessed by FACIT–Fatigue score exceeding the minimum clinically important difference of 4. Most adverse events were mild, but one each case of severe hypogammaglobulinemia, psychosis with suicidal behavior, and B‐cell lymphoma were occurred. In our first prospective real‐world study, telitacicept treatment led to a significant clinical and laboratory improvement of disease activity, as well as fatigue amelioration in patients with SLE. Safety profile was favorable overall, but more studies are greatly needed.
Frequent oil baths and skin barrier during infancy in the PreventADALL study
Authors: Eva Maria Rehbinder, Sabina Wärnberg Gerdin, Angela Hoyer, Maria Bradley, Karin C Lødrup Carlsen, Berit Granum, Gunilla Hedlin, Christine Monceyron Jonassen, Marissa Leblanc, Björn Nordlund, Knut Rudi, Håvard O Skjerven, Anne Cathrine Staff, Riyas Vettukattil, Cilla Söderhäll
Journal: British Journal of Dermatology (2024)

In the general population randomized controlled trial PreventADALL, frequent emollient bath additives from 2 weeks of age did not prevent atopic dermatitis, while the effect on skin barrier function throughout infancy is not established.
How to learn from interval cancers in colorectal cancer screening
Authors: Michael Bretthauer
Journal: Endoscopy (2024)

High quality performance is important to prevent colorectal cancers (CRCs) after colonoscopy. Therefore, we endoscopists are measured every day on our rates of cecal intubation, detection of polyps and adenomas, and patient satisfaction. That is great, and we support it. It helps us to understand our own performance in comparison to our peers, increases patient benefits, and reduces harms. After all, our endoscopies are there for the benefit of the people we treat: our patients.
Multifunctional Cu<sub>2</sub>Se/F127 Hydrogel with SOD‐Like Enzyme Activity for Efficient Wound Healing
Authors: Jia He, Wei Zhang, Yuyu Cui, Liang Cheng, Xu‐Lin Chen, Xianwen Wang
Journal: Advanced Healthcare Materials (2024)

Free radicals are secreted following skin damage and cause oxidative stress and inflammatory reactions that increase the difficulty of wound healing. In this study, copper-based nanozyme Cu
Use of a self-assembling peptide to control complications associated with endoscopic balloon dilation of refractory anastomotic stricture
Authors: Takehide Fukuchi, Shigeru Iwase, Kingo Hirasawa, Shin Maeda
Journal: Endoscopy (2024)

PuraStat (3-D Matrix, Tokyo, Japan) is a novel self-assembling peptide hydrogel developed as a hemostatic agent that is believed to be effective in reducing the risk of delayed perforation due to excessive cautery burns [1] [2] [3]. Additionally, studies in animal models have suggested the potential of PuraStat for preventing esophageal strictures after endoscopic submucosal dissection for esophageal cancer [4] [5]. In this report, we present a case in which the self-assembling peptide gel effectively managed esophageal stricture and safely addressed complications related to endoscopic balloon dilation (EBD) ([Video 1]).
Endoscopic submucosal dissection combined with endoscopic hand suturing for a laterally spreading tumor spanning the anastomosis after radical resection of a rectal carcinoma
Authors: Shibo Song, Yi Liu, Lizhou Dou, Guiqi Wang
Journal: Endoscopy (2024)

Precancerous lesions or early cancers located at the anastomosis after radical resection of a rectal carcinoma are relatively rare [1] [2]. Recently, several studies have suggested that endoscopic submucosal dissection (ESD) is a favorable treatment for such lesions [3] [4] [5]; however, because of severe adhesion in the submucosa of lesions that are located at the anastomosis, partial excision of the circular muscle layer may be required to prevent positive margins. We report a novel measure combining endoscopic hand suturing (EHS) with ESD, to close the postoperative defect following this, which is expected to be an ideal endoscopic method for precancerous lesions or early cancers that span the anastomosis after radical resection of a rectal carcinoma.
Comparative evaluation of a language model and human specialists in the application of European guidelines for the management of inflammatory bowel diseases and malignancies
Authors: Matti Waterman, Yuri Gorelik, Itai Ghersin, Roni Weisshof, Eduard Koifman, Haggai Bar-Yoseph, Dana Ben Hur, Itay Maza, Erez Hasnis, Roni Nasser, Baruch Ovadia, Dikla Dror Zur
Journal: Endoscopy (2024)

Abstract Background Society guidelines on colorectal dysplasia screening, surveillance, and endoscopic management in inflammatory bowel disease (IBD) are complex, and physician adherence to them is suboptimal. We aimed to evaluate the use of ChatGPT, a large language model, in generating accurate guideline-based recommendations for colorectal dysplasia screening, surveillance, and endoscopic management in IBD in line with European Crohn’s and Colitis Organization (ECCO) guidelines. Methods 30 clinical scenarios in the form of free text were prepared and presented to three separate sessions of ChatGPT and to eight gastroenterologists (four IBD specialists and four non-IBD gastroenterologists). Two additional IBD specialists subsequently assessed all responses provided by ChatGPT and the eight gastroenterologists, judging their accuracy according to ECCO guidelines. Results ChatGPT had a mean correct response rate of 87.8%. Among the eight gastroenterologists, the mean correct response rates were 85.8% for IBD experts and 89.2% for non-IBD experts. No statistically significant differences in accuracy were observed between ChatGPT and all gastroenterologists (P=0.95), or between ChatGPT and the IBD experts and non-IBD expert gastroenterologists, respectively (P=0.82). Conclusions This study highlights the potential of language models in enhancing guideline adherence regarding colorectal dysplasia in IBD. Further investigation of additional resources and prospective evaluation in real-world settings are warranted.
Cause‐specific death in heart failure across the ejection fraction spectrum: A comprehensive assessment of over 100 000 patients in the Swedish Heart Failure Registry
Authors: Camilla Settergren, Lina Benson, Angiza Shahim, Ulf Dahlström, Tonje Thorvaldsen, Gianluigi Savarese, Lars H. Lund, Bahira Shahim
Journal: European Journal of Heart Failure (2024)

Abstract Aim To assess cause‐specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). Methods and results Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000–2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66–82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non‐CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28–1.38, p &lt; 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82–0.88, p &lt; 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non‐CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non‐CV deaths due to cancer, respiratory disease, and infections increased with increasing EF. Conclusion Cardiovascular death was more common than non‐CV death across all EF categories although the risk of non‐CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non‐CV deaths, respectively, regardless of EF category.
Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells
Authors: Dalia Rosano, Emre Sofyali, Heena Dhiman, Chiara Ghirardi, Diana Ivanoiu, Timon Heide, Andrea Vingiani, Alessia Bertolotti, Giancarlo Pruneri, Eleonora Canale, Hannah F. Dewhurst, Debjani Saha, Neil Slaven, Iros Barozzi, Tong Li, Grigory Zemlyanskiy, Henry Phillips, Chela James, Balázs Győrffy, Claire Lynn, George D. Cresswell, Farah Rehman, Roberta Noberini, Tiziana Bonaldi, Andrea Sottoriva, Luca Magnani
Journal: Cancer Discovery (2024)

Abstract Patients with estrogen receptor–positive breast cancer receive adjuvant endocrine therapies (ET) that delay relapse by targeting clinically undetectable micrometastatic deposits. Yet, up to 50% of patients relapse even decades after surgery through unknown mechanisms likely involving dormancy. To investigate genetic and transcriptional changes underlying tumor awakening, we analyzed late relapse patients and longitudinally profiled a rare cohort treated with long-term neoadjuvant ETs until progression. Next, we developed an in vitro evolutionary study to record the adaptive strategies of individual lineages in unperturbed parallel experiments. Our data demonstrate that ETs induce nongenetic cell state transitions into dormancy in a stochastic subset of cells via epigenetic reprogramming. Single lineages with divergent phenotypes awaken unpredictably in the absence of recurrent genetic alterations. Targeting the dormant epigenome shows promising activity against adapting cancer cells. Overall, this study uncovers the contribution of epigenetic adaptation to the evolution of resistance to ETs. Significance: This study advances the understanding of therapy-induced dormancy with potential clinical implications for breast cancer. Estrogen receptor-positive breast cancer cells adapt to endocrine treatment by entering a dormant state characterized by strong heterochromatinization with no recurrent genetic changes. Targeting the epigenetic rewiring impairs the adaptation of cancer cells to ETs. See related commentary by Llinas-Bertran et al., p. 704. This article is featured in Selected Articles from This Issue, p. 695
Successful underwater endoscopic submucosal dissection with gel immersion for early gastric cancer in an upside-down stomach
Authors: Takahiro Muramatsu, Tomoaki Tashima, Tsubasa Ishikawa, Tomonori Kawasaki, Yumi Mashimo, Takao Itoi, Shomei Ryozawa
Journal: Endoscopy (2024)

An upside-down stomach (UDS) is a relatively rare type of esophageal hiatal hernia; almost the entire stomach prolapses into the posterior mediastinum in affected patients [1].
Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency
Authors: Hirotsugu Oda, Kalpana Manthiram, Pallavi Pimpale Chavan, Eva Rieser, Önay Veli, Öykü Kaya, Charles Rauch, Shuichiro Nakabo, Hye Sun Kuehn, Mariël Swart, Yanli Wang, Nisa Ilgim Çelik, Anne Molitor, Vahid Ziaee, Nasim Movahedi, Mohammad Shahrooei, Nima Parvaneh, Nasrin Alipour-olyei, Raphael Carapito, Qin Xu, Silvia Preite, David B. Beck, Jae Jin Chae, Michele Nehrebecky, Amanda K. Ombrello, Patrycja Hoffmann, Tina Romeo, Natalie T. Deuitch, Brynja Matthíasardóttir, James Mullikin, Hirsh Komarow, Jennifer Stoddard, Julie Niemela, Kerry Dobbs, Colin L. Sweeney, Holly Anderton, Kate E. Lawlor, Hiroyuki Yoshitomi, Dan Yang, Manfred Boehm, Jeremy Davis, Pamela Mudd, Davide Randazzo, Wanxia Li Tsai, Massimo Gadina, Mariana J. Kaplan, Junya Toguchida, Christian T. Mayer, Sergio D. Rosenzweig, Luigi D. Notarangelo, Kazuhiro Iwai, John Silke, Pamela L. Schwartzberg, Bertrand Boisson, Jean-Laurent Casanova, Seiamak Bahram, Anand Prahalad Rao, Nieves Peltzer, Henning Walczak, Najoua Lalaoui, Ivona Aksentijevich, Daniel L. Kastner
Journal: Nature Immunology (2024)
Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis
Authors: Marisol Alvarez-Martinez, Luke S. Cox, Claire F. Pearson, William J. Branchett, Probir Chakravarty, Xuemei Wu, Hubert Slawinski, Alaa Al-Dibouni, Vasileios A. Samelis, Leona Gabryšová, Simon L. Priestnall, Alejandro Suárez-Bonnet, Anna Mikolajczak, James Briscoe, Fiona Powrie, Anne O’Garra
Journal: Nature Immunology (2024)

Abstract Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4 + T cells to show that the transcription factors Blimp-1 (encoded by Prdm1 ) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1 fl/fl Maf fl/fl Cd4 Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in T H 1/NK/ILC1 effector genes in LPLs, while Prdm1 fl/fl Cd4 Cre and Maf fl/fl Cd4 Cre mice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maf fl/fl Cd4 Cre mice had increased type 17 responses with increased Il17a and Il22 expression and an increase in granulocytes and myeloid cell numbers, resulting in increased T cell–myeloid–neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1 or Maf , revealing potential mechanisms of human disease.
Fast and Comfortable Interactive Mobile Robot-to-Human Object Handover
Authors: Chongxi Meng, Tianwei Zhang, Da Zhao, Tin Lun Lam
Journal: Cyborg and Bionic Systems (2024)

In this work, we present a method that enables a mobile robot to hand over objects to humans efficiently and safely by combining mobile navigation with visual perception. Our robotic system can map its environment in real time and locate objects to pick up. It uses advanced algorithms to grasp objects in a way that suits human preference and employs path planning and obstacle avoidance to navigate back to the human user. The robot adjusts its movements during handover by analyzing the human’s posture and movements through visual sensors, ensuring a smooth and collision-free handover. Tests of our system show that it can successfully hand over various objects to humans and adapt to changes in the human’s hand position, highlighting improvements in safety and versatility for robotic handovers.