tbuckley/cabot-search huggingface dataset:
Challenges and prospects of visual contactless physiological monitoring in clinical study
Authors: Bin Huang, Shen Hu, Zimeng Liu, Chun-Liang Lin, Junfeng Su, Changchen Zhao, Li Wang, Wenjin Wang
Journal: npj Digital Medicine (2023)

The monitoring of physiological parameters is a crucial topic in promoting human health and an indispensable approach for assessing physiological status and diagnosing diseases. Particularly, it holds significant value for patients who require long-term monitoring or with underlying cardiovascular disease. To this end, Visual Contactless Physiological Monitoring (VCPM) is capable of using videos recorded by a consumer camera to monitor blood volume pulse (BVP) signal, heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2) and blood pressure (BP). Recently, deep learning-based pipelines have attracted numerous scholars and achieved unprecedented development. Although VCPM is still an emerging digital medical technology and presents many challenges and opportunities, it has the potential to revolutionize clinical medicine, digital health, telemedicine as well as other areas. The VCPM technology presents a viable solution that can be integrated into these systems for measuring vital parameters during video consultation, owing to its merits of contactless measurement, cost-effectiveness, user-friendly passive monitoring and the sole requirement of an off-the-shelf camera. In fact, the studies of VCPM technologies have been rocketing recently, particularly AI-based approaches, but few are employed in clinical settings. Here we provide a comprehensive overview of the applications, challenges, and prospects of VCPM from the perspective of clinical settings and AI technologies for the first time. The thorough exploration and analysis of clinical scenarios will provide profound guidance for the research and development of VCPM technologies in clinical settings.
Improvements in Survival and Clinical Benefit With Gemcitabine as First-Line Therapy for Patients With Advanced Pancreas Cancer: A Randomized Trial
Authors: H A Burris, M J Moore, J Andersen, M R Green, M L Rothenberg, M R Modiano, M C Cripps, R K Portenoy, A M Storniolo, P Tarassoff, R Nelson, F A Dorr, C D Stephens, D D Von Hoff
Journal: Journal of Clinical Oncology (2023)

Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer.
Indications for adjuvant radiotherapy in high-risk squamous cell carcinoma with clear margins: a Delphi consensus
Authors: Elvira Moscarella, Eugenia Veronica Di Brizzi, Paolo Alpi, Alessandra Arcelli, Serena Badellino, Paolo Bossi, Pier Giacomo Calzavara-Pinton, Alessandro Di Stefani, Emi Dika, Laura Eibenschutz, Maria Concetta Fargnoli, Bruno Fionda, Giovanni Luca Gravina, Barbara Grilli Leonulli, Caterina Longo, Lucia Lospalluti, Valerio Nardone, Nicola Pimpinelli, Pietro Quaglino, Paola Queirolo, Pietro Rubegni, Luca Tagliaferri, Teresa Troiani, Andrea Vavassori, Giuseppe Argenziano
Journal: British Journal of Dermatology (2023)

The aim of this study was to provide indications for adjuvant radiotherapy in high-risk cutaneous squamous cell carcinoma.
Defining curative endpoints for transfusion‐dependent β‐thalassemia in the era of gene therapy and gene editing
Authors: Selim Corbacioglu, Haydar Frangoul, Franco Locatelli, William Hobbs, Mark Walters
Journal: American Journal of Hematology (2023)

β-thalassemia is a monogenic disease that results in varying degrees of anemia. In the most severe form, known as transfusion-dependent β-thalassemia (TDT), the clinical hallmarks are ineffective erythropoiesis and a requirement of regular, life-long red blood cell transfusions, with the development of secondary clinical complications such as iron overload, end-organ damage, and a risk of early mortality. With the exception of allogeneic hematopoietic cell transplantation, current treatments for TDT address disease symptoms and not the underlying cause of disease. Recently, a growing number of gene addition and gene editing-based treatments for patients with TDT with the potential to provide a one-time functional cure have entered clinical trials. A key challenge in the design and evaluation of these trials is selecting endpoints to evaluate if these novel genetic therapies have a curative versus an ameliorative effect. Here, we present an overview of the pathophysiology of TDT, review emerging gene addition or gene editing therapeutic approaches for TDT currently in clinical trials, and identify a series of endpoints that can quantify therapeutic effects, including a curative outcome.
Remodelling of cAMP dynamics within the SERCA2a microdomain in heart failure with preserved ejection fraction caused by obesity and type 2 diabetes
Authors: Ping Lai, Susanne S Hille, Hariharan Subramanian, Robert Wiegmann, Pia Roser, Oliver J Müller, Viacheslav O Nikolaev, Kirstie A De Jong
Journal: Cardiovascular Research (2023)

Abstract Aims Despite massive efforts, we remain far behind in our attempts to identify effective therapies to treat heart failure with preserved ejection fraction (HFpEF). Diastolic function is critically regulated by sarcoplasmic/endoplasmic reticulum (SR) calcium ATPase 2a (SERCA2a), which forms a functional cardiomyocyte (CM) microdomain where 3′,5′-cyclic adenosine monophosphate (cAMP) produced upon β-adrenergic receptor (β-AR) stimulation leads to phospholamban (PLN) phosphorylation and facilitated Ca2+ re-uptake. Methods and results To visualize real-time cAMP dynamics in the direct vicinity of SERCA2a in healthy and diseased myocytes, we generated a novel mouse model on the leprdb background that stably expresses the Epac1-PLN Förster resonance energy transfer biosensor. Mice homozygous for the leprdb mutation (db/db) developed obesity and type 2 diabetes and presented with a HFpEF phenotype, evident by mild left ventricular hypertrophy and elevated left atria filling pressures. Live cell imaging uncovered a substantial β2-AR subtype stimulated cAMP response within the PLN/SERCA2a microdomain of db/db but not healthy control (db/+) CMs, which was accompanied by increased PLN phosphorylation and accelerated calcium re-uptake. Importantly, db/db CMs also exhibited a desensitization of β1-AR stimulated cAMP pools within the PLN/SERCA2a microdomain, which was accompanied by a blunted lusitropic effect, suggesting that the increased β2-AR control is an intrinsic compensatory mechanism to maintain PLN/SERCA2a-mediated calcium dynamics and cardiac relaxation. Mechanistically, this was due to a local loss of cAMP-degrading phosphodiesterase 4 associated specifically with the PLN/SERCA2a complex. Conclusion These newly identified alterations of cAMP dynamics at the subcellular level in HFpEF should provide mechanistic understanding of microdomain remodelling and pave the way towards new therapies.
Delusions of parasitosis: A retrospective case control study examining biometric and pharmaceutical associations
Authors: Anissa Bernardez, Debolina Kanjilal, An-Lin Cheng, Colleen Reisz
Journal: Journal of the American Academy of Dermatology (2023)

To the Editor: Delusions of parasitosis (DOP) predominates in middle-aged women and has associations with renal failure and some medications.1 A recent study found that afflicted patients often have other psychiatric conditions.2 We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in clearance capacity. Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.
Dual‐Frequency Ultrasound Assisted Thrombolysis in Interventional Therapy of Deep Vein Thrombosis
Authors: Yunfan Pan, Yongjian Li, Yuexin Chen, Jiang Li, Haosheng Chen
Journal: Advanced Healthcare Materials (2023)

Deep vein thrombosis (DVT) is one of the main causes of disability and death worldwide. Currently, the treatment of DVT still needs a long time and faces a high risk of major bleeding. It is necessary to find a rapid and safe method for the therapy of DVT. Here, a dual-frequency ultrasound assisted thrombolysis (DF-UAT) is reported for the interventional treatment of DVT. A series of piezoelectric elements are placed in an interventional catheter to emit ultrasound waves with two independent frequencies in turn. The low-frequency ultrasound drives the drug-loaded droplets into the thrombus, while the high-frequency ultrasound causes the cavitation of the droplets in the thrombus. With the joint effect of the enhanced drug diffusion and the cavitation under the dual-frequency ultrasound, the thrombolytic efficacy can be improved. In a proof-of-concept experiment performed with living sheep, the recanalization of the iliac vein is realized in 15 min using the DF-UAT technology. Therefore, the DF-UAT can be one of the most promising methods in the interventional treatment of DVT.
A pH/ROS dual-responsive system for effective chemoimmunotherapy against melanoma via remodeling tumor immune microenvironment
Authors: Leilei Wang, Shanshan He, Rong Liu, Yuan Xue, Yuan Quan, Rongying Shi, Xueying Yang, Qing Lin, Xun Sun, Zhirong Zhang, Ling Zhang
Journal: Acta Pharmaceutica Sinica B (2023)

Chemotherapeutics can induce immunogenic cell death (ICD) in tumor cells, offering new possibilities for cancer therapy. However, the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment (TME). Here, we developed a pH/reactive oxygen species (ROS) dual-response system to enhance chemoimmunotherapy for melanoma. The system productively accumulated in tumors by specific binding of phenylboronic acid (PBA) to sialic acids (SA). The nanoparticles (NPs) rapidly swelled and released quercetin (QUE) and doxorubicin (DOX) upon the stimulation of tumor microenvironment (TME). The
Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1
Authors: Shanshan Rao, Zehui He, Zun Wang, Hao Yin, Xiongke Hu, Yijuan Tan, Tengfei Wan, Hao Zhu, Yi Luo, Xin Wang, Hongming Li, Zhenxing Wang, Xinyue Hu, Chungu Hong, Yiyi Wang, Mingjie Luo, Wei Du, Yuxuan Qian, Siyuan Tang, Hui Xie, Chunyuan Chen
Journal: Acta Pharmaceutica Sinica B (2023)

Aging increases the risks of various diseases and the vulnerability to death. Cellular senescence is a hallmark of aging that contributes greatly to aging and aging-related diseases. This study demonstrates that extracellular vesicles from human urine-derived stem cells (USC-EVs) efficiently inhibit cellular senescence
EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway
Authors: Yongyun Li, Tianyu Zhu, Jie Yang, Qianqian Zhang, Shiqiong Xu, Shengfang Ge, Renbing Jia, Jianming Zhang, Xianqun Fan
Journal: Acta Pharmaceutica Sinica B (2023)

Constitutive activation of
Small-molecule agents for cancer immunotherapy
Authors: Fang Wang, Kai Fu, Yujue Wang, Can Pan, Xueping Wang, Zeyu Liu, Chuan Yang, Ying Zheng, Xiaopeng Li, Yu Lu, Kenneth Kin Wah To, Chenglai Xia, Jianye Zhang, Zhi Shi, Zeping Hu, Min Huang, Liwu Fu
Journal: Acta Pharmaceutica Sinica B (2023)

Cancer immunotherapy, exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy, is revolutionizing cancer therapy. They induce long-term tumor regression and overall survival benefit in many types of cancer. With the advances in our knowledge about the tumor immune microenvironment, remarkable progress has been made in the development of small-molecule drugs for immunotherapy. Small molecules targeting PRR-associated pathways, immune checkpoints, oncogenic signaling, metabolic pathways, cytokine/chemokine signaling, and immune-related kinases have been extensively investigated. Monotherapy of small-molecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance. Here, we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.
Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy
Authors: Qi Shang, Wandong Liu, Faith Leslie, Jiapei Yang, Mingmei Guo, Mingjiao Sun, Guangji Zhang, Qiang Zhang, Feihu Wang
Journal: Acta Pharmaceutica Sinica B (2023)

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.
Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy
Authors: Renming Fan, Ruizhuo Lin, Shuo Zhang, Aohua Deng, Yongrui Hai, Junyan Zhuang, Yang Liu, Maosheng Cheng, Gaofei Wei
Journal: Acta Pharmaceutica Sinica B (2023)

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to the activation of cellular oxidative stress and immune responses. While the role of mitochondrial membrane remodeling in promoting inflammation in hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which is composed of oxaliplatin (Oxa) and acetaminophen (APAP), to enhance its anti-tumor effects and amplify the immune response. Our findings demonstrate that OAP2 induces nuclear DNA damage, resulting in the production of nuclear DNA. Additionally, OAP2 downregulates the expression of mitochondrial Sam50, to promote mitochondrial membrane remodeling and trigger mtDNA secretion, leading to double-stranded DNA accumulation and ultimately synergistically activating the intracellular cGAS-STING pathway. The mitochondrial membrane remodeling induced by OAP2 overcomes the limitations of Oxa in activating the STING pathway and simultaneously promotes gasdermin-D-mediated cell pyroptosis. OAP2 also promotes dendritic cell maturation and enhances the quantity and efficacy of cytotoxic T cells, thereby inhibiting cancer cell proliferation and metastasis. Briefly, our study introduces the first novel small-molecule inhibitor that regulates mitochondrial membrane remodeling for active immunotherapy in anti-tumor research, which may provide a creative idea for targeting organelle in anti-tumor therapy.
Engineered mischarged transfer RNAs for correcting pathogenic missense mutations
Authors: Yichen Hou, Wen Zhang, Philip T. McGilvray, Marek Sobczyk, Tianxin Wang, Shao Huan Samuel Weng, Allen Huff, Sihao Huang, Noah Pena, Christopher D. Katanski, Tao Pan
Journal: Molecular Therapy (2023)
Post-colonoscopy colorectal cancers in a national fecal immunochemical test-based colorectal cancer screening program
Authors: Pieter H. A. Wisse, Sybrand Y. de Boer, Marco Oudkerk Pool, Jochim S Terhaar sive Droste, Claudia Verveer, Gerrit A. Meijer, Evelien Dekker, Manon C. W. Spaander
Journal: Endoscopy (2023)

Abstract Background Post-colonoscopy colorectal cancers (PCCRCs) decrease the effect of colorectal cancer (CRC) screening programs. To enable PCCRC incidence reduction in the long-term, we classified PCCRCs diagnosed after colonoscopies performed in a fecal immunochemical test (FIT)-based screening program. Methods PCCRCs diagnosed after colonoscopies performed between 2014–2016 for a positive FIT in the Dutch CRC screening program were included. PCCRCs were categorized according to the World Endoscopy Organization consensus statement into (a) interval PCCRC (diagnosed before the recommended surveillance); (b) non-interval type A (diagnosed at the recommended surveillance interval); (c) non-interval type B (diagnosed after the recommended surveillance interval); or (d) non-interval type C (diagnosed after the intended recommended surveillance interval, with surveillance not implemented owing to co-morbidity). The most probable etiology was determined by root-cause analysis. Tumor stage distributions were compared between categories. Results 116362 colonoscopies were performed after a positive FIT with 9978 screen-detected CRCs. During follow-up, 432 PCCRCs were diagnosed. The 3-year PCCRC rate was 2.7%. PCCRCs were categorized as interval (53.5%), non-interval type A (14.6%), non-interval type B (30.6%), and non-interval type C (1.4%). The most common etiology for interval PCCRCs was possible missed lesion with adequate examination (73.6%); they were more often diagnosed at an advanced stage (stage III/IV; 53.2%) compared with non-interval type A (15.9%; P&lt;0.001) and non-interval type B (40.9%; P=0.03) PCCRCs. Conclusions The 3-year PCCRC rate was low in this FIT-based CRC screening program. Approximately half of PCCRCs were interval PCCRCs. These were mostly caused by missed lesions and were diagnosed at a more advanced stage. This emphasizes the importance of high quality colonoscopy with optimal polyp detection.
The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies
Authors: Longsheng Wang, Jie Zhang, Wenxin Zhang, Mingming Zheng, Hongjie Guo, Xiaohui Pan, Wen Li, Bo Yang, Ling Ding
Journal: Acta Pharmaceutica Sinica B (2023)

Adenosine (Ado) is significantly elevated in the tumor microenvironment (TME) compared to normal tissues. It binds to adenosine receptors (AdoRs), suppressing tumor antigen presentation and immune cell activation, thereby inhibiting tumor adaptive immunity. Ado downregulates major histocompatibility complex II (MHC II) and co-stimulatory factors on Dendritic cells (DCs) and macrophages, inhibiting antigen presentation. It suppresses anti-tumor cytokine secretion and T cell activation by disrupting T cell receptor (TCR) binding and signal transduction. Ado also inhibits chemokine secretion and KCa3.1 channel activity, impeding effector T cell trafficking and infiltration into the tumor site. Furthermore, Ado diminishes T cell cytotoxicity against tumor cells by promoting immune-suppressive cytokine secretion, upregulating immune checkpoint proteins, and enhancing immune-suppressive cell activity. Reducing Ado production in the TME can significantly enhance anti-tumor immune responses and improve the efficacy of other immunotherapies. Preclinical and clinical development of inhibitors targeting Ado generation or AdoRs is underway. Therefore, this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity, as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses.
Hurdles in translating science from lab to market in delivery systems for Cosmetics: An industrial perspective
Authors: Sheila Siqueira Andrade, Alessandra Valéria de Sousa Faria, Alioscka Augusto Sousa, Rodrigo da Silva Ferreira, Nichollas Serafim Camargo, Mosar Corrêa Rodrigues, João Paulo Figueiró Longo
Journal: Advanced Drug Delivery Reviews (2023)
Trajectory analysis of rhinitis in a birth cohort from lower-income New York City neighborhoods
Authors: Nina M. Flores, Stephanie Lovinsky-Desir, Adnan Divjan, Lori A. Hoepner, Jungang Zou, Rachel L. Miller, Julie B. Herbstman, Frederica P. Perera, Matthew S. Perzanowski, Qixuan Chen
Journal: Journal of Allergy and Clinical Immunology (2023)
Association of systemic inflammatory markers and tertiary lymphoid structure with pathological complete response in gastric cancer patients receiving preoperative treatment: a retrospective cohort study
Authors: Yingying Wu, Junjie Zhao, Zhaoming Wang, Dan Liu, Chenyu Tian, Botian Ye, Yihong Sun, Haojie Li, Xuefei Wang
Journal: International Journal of Surgery (2023)

Background: Assessment of systemic and local immune responses is crucial in determining the efficacy of cancer interventions. The identification of specific factors that correlate with pathological complete response (pCR) is essential for optimizing treatment decisions. Methods: In this retrospective study, a total of 521 patients diagnosed with gastric adenocarcinoma who underwent curative gastrectomy following preoperative treatment were reviewed. Of these patients, 463 did not achieve pCR (non-pCR) and 58 achieved pCR. Clinicopathological factors were evaluated to identify predictors for pCR using a logistic regression model. Additionally, a smaller cohort ( n =76) was derived using propensity score matching to investigate local immune response, specifically the features of tertiary lymphoid structure (TLS) using H&amp;E staining, immunohistochemistry, and multiplex immunofluorescence. Results: The multivariate regression analysis demonstrated a significant association between low systemic inflammatory status and pCR, as evidenced by reduced levels of the combined systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) (SII+NLR) (odds ratio: 3.33, 95% CI: 1.79–6.17, P &lt;0.001). In the smaller cohort analysis, distinct TLS characteristics were correlated with the presence of pCR. Specifically, a higher density of TLS and a lower proportion of PD1+ cells and CD8+ cells within TLS in the tumor bed were strongly associated with pCR. Conclusion: Both systemic and local immune profile were associated with pCR. A low level of SII+NLR served as an independent predictor of pCR, while distinct TLS features were associated with the presence of pCR. Focusing on the immune profile was crucial for optimal management of gastric cancer patients receiving preoperative treatment.
Use of disposable endoscope for variceal sclerotherapy
Authors: Kisako Fujiwara, Takayuki Kondo, Kentaro Fujimoto, Mai Fujie, Naoya Kanogawa, Sadahisa Ogasawara, Naoya Kato
Journal: Endoscopy (2023)

Diagnostic esophagogastric endoscopy has recently been performed using new sterile single-use disposable endoscopes (Ambu aScope Gastro; Ambu, Ballerup, Denmark) ([Fig. 1]) due to the potential risk of cross-infection associated with reusable endoscopes [1] [2].
Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR
Authors: Evangelia Kokalaki, Biao Ma, Mathieu Ferrari, Thomas Grothier, Warren Hazelton, Somayya Manzoor, Eren Costu, Julia Taylor, Anna Bulek, Saket Srivastava, Isaac Gannon, Ram Jha, Rosalind Gealy, Lukas Stanczuk, Tatiana Rizou, Mathew Robson, Mohamed El-Kholy, Vania Baldan, Matteo Righi, James Sillibourne, Simon Thomas, Shimobi Onuoha, Shaun Cordoba, Martin Pule
Journal: Molecular Therapy (2023)
School bullying in children and adolescents with neurodevelopmental and psychiatric conditions: a systematic review and meta-analysis
Authors: Renzo Abregú-Crespo, Alexandra Garriz-Luis, Miriam Ayora, Nuria Martín-Martínez, Vito Cavone, Miguel Ángel Carrasco, David Fraguas, Javier Martín-Babarro, Celso Arango, Covadonga M Díaz-Caneja
Journal: The Lancet Child & Adolescent Health (2023)