tbuckley/cabot-search huggingface dataset:
5,7,4′‐Trimethoxyflavone triggers cancer cell PD‐L1 ubiquitin–proteasome degradation and facilitates antitumor immunity by targeting HRD1
Authors: Jianhua Xia, Mengting Xu, Hongmei Hu, Qing Zhang, Dianping Yu, Minchen Cai, Xiangxin Geng, Hongwei Zhang, Yanyan Zhang, Mengmeng Guo, Dong Lu, Hanchi Xu, Linyang Li, Xing Zhang, Qun Wang, Sanhong Liu, Weidong Zhang
Journal: MedComm (2024)

Abstract Targeting the programmed cell death 1/programmed cell death ligand 1 (PD‐1/PD‐L1) pathway has been identified as a successful approach for tumor immunotherapy. Here, we identified that the small molecule 5,7,4′‐trimethoxyflavone (TF) from Kaempferia parviflora Wall reduces PD‐L1 expression in colorectal cancer cells and enhances the killing of tumor cells by T cells. Mechanistically, TF targets and stabilizes the ubiquitin ligase HMG‐CoA reductase degradation protein 1 (HRD1), thereby increasing the ubiquitination of PD‐L1 and promoting its degradation through the proteasome pathway. In mouse MC38 xenograft tumors, TF can activate tumor‐infiltrating T‐cell immunity and reduce the immunosuppressive infiltration of myeloid‐derived suppressor cells and regulatory T cells, thus exerting antitumor effects. Moreover, TF synergistically exerts antitumor immunity with CTLA‐4 antibody. This study provides new insights into the antitumor mechanism of TF and suggests that it may be a promising small molecule immune checkpoint modulator for cancer therapy.
Associations of blood pressure in the third trimester and risk of venous thromboembolism postpartum
Authors: Qian Li, Hongfei Wang, Huafang Wang, Jun Deng, Zhipeng Cheng, Fengjuan Fan, Wenyi Lin, Ruiqi Zhu, Shi Chen, Jinrong Guo, Yuxiong Weng, Liang V. Tang, Yu Hu
Journal: MedComm (2024)

Abstract Studies on the associations of blood pressure (BP) and the risk of venous thromboembolism (VTE) had been performed neither among pregnant women nor in Chinese population. This study included participants of pregnant women from a retrospective multicenter cohort, between May 2020 and April 2023. Systolic BP (SBP) and diastolic BP (DBP) of the participants were measured in the third trimester. The incidences of VTE (including deep venous thrombosis and/or pulmonary embolism) at 42 days postpartum were followed. With regards to SBP, pregnant women in the Q1 (≤114 mmHg), Q2 (115–122 mmHg), and Q4 group (≥131 mmHg) had increased risk of VTE than those in Q3 group (123–130 mmHg), with ORs 4.48 [1.69, 11.85], 3.52 [1.30, 9.59], and 3.17 [1.12, 8.99], respectively. Compared with pregnant women with the Q4 of DBP (≥85 mmHg), women of Q1 (≤71 mmHg) were found to have elevated risk of VTE (OR 2.73 [1.25, 5.96]). A one standard deviation decrease of DBP (9 mmHg) was related with 37% elevated risk of VTE (OR 1.37 [1.05, 1.79]). This study demonstrated a U‐shaped association of SBP in the third trimester and VTE postpartum and inverse association of DBP in the third trimester and VTE postpartum.
Long‐term tafamidis efficacy in patients with transthyretin amyloid cardiomyopathy by baseline left ventricular ejection fraction
Authors: Brian Drachman, Thibaud Damy, Mazen Hanna, Ronnie Wang, Franca S. Angeli, Pablo Garcia‐Pavia
Journal: European Journal of Heart Failure (2024)

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) present with diverse left ventricular ejection fraction (LVEF). This study assessed tafamidis efficacy by baseline LVEF in the phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and its long-term extension (LTE) study.
Cardiovascular‐kidney‐metabolic overlap in heart failure with preserved ejection fraction: Cardiac structure and function, clinical outcomes, and response to sacubitril/valsartan in PARAGON‐HF
Authors: Mats C.H. Lassen, John W. Ostrominski, Brian L. Claggett, Milton Packer, Michael Zile, Akshay S. Desai, Amil M. Shah, Maja Cikes, Bela Merkely, Mauro Gori, Xiaowen Wang, Sheila M. Hegde, Marc A. Pfeffer, Martin Lefkowitz, John J.V. McMurray, Scott D. Solomon, Muthiah Vaduganathan
Journal: European Journal of Heart Failure (2024)
Effects of canagliflozin on total heart failure events across the kidney function spectrum: Participant‐level pooled analysis from the <scp>CANVAS</scp> Program and <scp>CREDENCE</scp> trial
Authors: Muthiah Vaduganathan, Christopher P. Cannon, Meg J. Jardine, Hiddo J.L. Heerspink, Clare Arnott, Brendon L. Neuen, Ashish Sarraju, Jagadish Gogate, Jochen Seufert, Bruce Neal, Vlado Perkovic, Kenneth W. Mahaffey, Mikhail N. Kosiborod
Journal: European Journal of Heart Failure (2024)
Role of noninvasive tests in the prognostication of metabolic dysfunction-associated steatotic liver disease
Authors: Yue Wang, Sherlot Juan Song, Yichong Jiang, Jimmy Che-To Lai, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
Journal: Clinical and Molecular Hepatology (2024)

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial.The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings.They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications.Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications.Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker.For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis.Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis; and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy.Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings.Expanding their future use in clinical practice depends on factors such as cost and facility availability.
Caffeine Inhibits Both Basal and Insulin‐Activated Urate Transport
Authors: Asim K. Mandal, Tony R. Merriman, Hyon K. Choi, David B. Mount
Journal: Arthritis & Rheumatology (2024)

Caffeine, an adenosine receptor antagonist, is a potent central nervous system stimulant that also impairs insulin signaling. Recent studies have suggested that coffee consumption lowers serum urate (SU) and protects against gout by unknown mechanisms. We hypothesized that caffeine lowers SU by affecting activity of urate transporters.
A multi-center study on the adaptability of a shared foundation model for electronic health records
Authors: Lin Lawrence Guo, Jason Fries, Ethan Steinberg, Scott Lanyon Fleming, Keith Morse, Catherine Aftandilian, Jose Posada, Nigam Shah, Lillian Sung
Journal: npj Digital Medicine (2024)

Foundation models are transforming artificial intelligence (AI) in healthcare by providing modular components adaptable for various downstream tasks, making AI development more scalable and cost-effective. Foundation models for structured electronic health records (EHR), trained on coded medical records from millions of patients, demonstrated benefits including increased performance with fewer training labels, and improved robustness to distribution shifts. However, questions remain on the feasibility of sharing these models across hospitals and their performance in local tasks. This multi-center study examined the adaptability of a publicly accessible structured EHR foundation model (FM
Artificial intelligence and personalized diagnostics in periodontology: A narrative review
Authors: Vinay Pitchika, Martha Büttner, Falk Schwendicke
Journal: Periodontology 2000 (2024)

Periodontal diseases pose a significant global health burden, requiring early detection and personalized treatment approaches. Traditional diagnostic approaches in periodontology often rely on a "one size fits all" approach, which may overlook the unique variations in disease progression and response to treatment among individuals. This narrative review explores the role of artificial intelligence (AI) and personalized diagnostics in periodontology, emphasizing the potential for tailored diagnostic strategies to enhance precision medicine in periodontal care. The review begins by elucidating the limitations of conventional diagnostic techniques. Subsequently, it delves into the application of AI models in analyzing diverse data sets, such as clinical records, imaging, and molecular information, and its role in periodontal training. Furthermore, the review also discusses the role of research community and policymakers in integrating personalized diagnostics in periodontal care. Challenges and ethical considerations associated with adopting AI-based personalized diagnostic tools are also explored, emphasizing the need for transparent algorithms, data safety and privacy, ongoing multidisciplinary collaboration, and patient involvement. In conclusion, this narrative review underscores the transformative potential of AI in advancing periodontal diagnostics toward a personalized paradigm, and their integration into clinical practice holds the promise of ushering in a new era of precision medicine for periodontal care.
The use of patient‐related outcomes (<scp>PRO</scp>) and experience (<scp>PRE</scp>) in assessing the periodontal and implant patient
Authors: Sirikarn P. Arunyanak, Kajorn Kungsadalpipob, Kyle E. Wright, Keskanya Subbalekha, Irina Dragan, Nikos Mattheos
Journal: Periodontology 2000 (2024)

The purpose of this review was to summarize the evidence with regard to behavioral and psychosocial assessment of the periodontitis patient, the candidate for implant therapy, and the peri-implantitis patient. Periodontitis has an adverse effect on quality of life and its treatment can lead to significant improvements experienced by the patient. The latter is true for rehabilitation with dental implants, although patients harbor diverse expectations and perceptions of implant therapy, which can often interfere with satisfaction and/or influence long-term success. A thorough behavioral assessment of the candidate for implant therapy is essential, which should include, perceptions, expectations, as well as risk for behavioral disorders. Remedial action is essential to correct misperceptions and any identified risks. Finally, patients have limited awareness of limited ability to identify signs of peri-implantitis. The diagnosis of peri-implantitis can be a cause of significant distress, resentment, and loss of trust to the treatment and the caregivers. Despite documented value in clinical research, currently available instruments assessing patient-reported outcomes have little application in day-to-day clinical practice. Face-to-face patient to doctor open-ended communication remains the most effective way to comprehensively establish the long-term "therapeutic alliance" essential for the long journey for the periodontitis patient.
Unraveling host genetics and microbiome genome crosstalk: a novel therapeutic approach
Authors: Qian Zhang, Dennis Schwarz, Yumei Cheng, Yahya Sohrabi
Journal: Trends in Molecular Medicine (2024)

The ability of the gut microbiome to adapt to a new environment and utilize a new metabolite or dietary compound by inducing structural variations (SVs) in the genome has an important role in human health. Here, we discuss recent data on host genetic regulation of SV induction and its use as a new therapeutic approach.
Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer’s Disease
Authors: Maria Luisa De Paolis, Ilaria Paoletti, Claudio Zaccone, Fioravante Capone, Marcello D’Amelio, Paraskevi Krashia
Journal: Translational Neurodegeneration (2024)

Abstract The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer’s Disease (AD) and to testing new drugs, with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments, such as non-invasive stimulation techniques on AD neuropathology and symptoms. Among the different non-invasive brain stimulation approaches, transcranial alternating current stimulation (tACS) is gaining particular attention due to its ability to externally control gamma oscillations. Here, we outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD, applied specifically at 40 Hz frequency, and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials.
Maximizing Treatment Opportunities: Assessing Protocol Waivers’ Impact on Safety and Outcome in the Drug Rediscovery Protocol
Authors: Jade M. van Berge Henegouwen, Laurien J. Zeverijn, Birgit S. Geurts, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Alwin D.R. Huitema, Filip Y.F. de Vos, Katrien Grünberg, Haiko J. Bloemendal, Henk M.W. Verheul, Emile E. Voest, Hans Gelderblom
Journal: Clinical Cancer Research (2024)

Although eligibility criteria are essential in trial design, overly restrictive criteria contribute to low accrual and limited generalizability. To enhance trial inclusivity, there has been growing interest in broadening eligibility criteria, especially for patients with advanced or treatment-refractory disease. Yet, the impact on patient safety remains uncertain. In the Drug Rediscovery Protocol (DRUP), protocol exceptions are frequently requested and occasionally granted. Here we describe the impact of these waivers on treatment safety and efficacy.
Tumor cell-released autophagosomes (TRAPs) induce PD-L1-decorated NETs that suppress T-cell function to promote breast cancer pulmonary metastasis
Authors: Xiaohe Zhou, Chengdong Wu, Xuru Wang, Ning Pan, Xiaotong Sun, Bohao Chen, Shiya Zheng, Yiting Wei, Jing Chen, Yuyang Wu, Fengjiao Zhu, Jinpeng Chen, Huabiao Chen, Li-xin Wang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Lung metastasis is the primary cause of breast cancer-related mortality. Neutrophil extracellular traps (NETs) are involved in the progression of breast cancer. However, the mechanism of NET formation is not fully understood. This study posits that tumor cell-released autophagosomes (TRAPs) play a crucial role in this process. Methods TRAPs were isolated from breast cancer cell lines to analyze their impact on NET formation in both human and mouse neutrophils. The study used both in vitro and in vivo models, including Toll-like receptor 4 (TLR4 − / − ) mice and engineered breast cancer cell lines. Immunofluorescence, ELISA, Western blotting, RNA sequencing, and flow cytometry were employed to dissect the signaling pathways leading to NET production and to explore their immunosuppressive effects, particularly focusing on the impact of NETs on T-cell function. The therapeutic potential of targeting TRAP-induced NETs and their immunosuppressive functions was evaluated using DNase I and αPD-L1 antibodies. Clinical relevance was assessed by correlating circulating levels of TRAPs and NETs with lung metastasis in patients with breast cancer. Results This study showed that TRAPs induced the formation of NETs in both human and mouse neutrophils by using the high mobility group box 1 and activating the TLR4-Myd88-ERK/p38 signaling axis. More importantly, PD-L1 carried by TRAP-induced NETs inhibited T-cell function in vitro and in vivo, thereby contributing to the formation of lung premetastatic niche (PMN) immunosuppression. In contrast, Becn1 KD-4T1 breast tumors with decreased circulating TRAPs in vivo reduced the formation of NETs, which in turn attenuated the immunosuppressive effects in PMN and resulted in a reduction of breast cancer pulmonary metastasis in murine models. Moreover, treatment with αPD-L1 in combination with DNase I that degraded NETs restored T-cell function and significantly reduced tumor metastasis. TRAP levels in the peripheral blood positively correlated with NET levels and lung metastasis in patients with breast cancer. Conclusions Our results demonstrate a novel role of TRAPs in the formation of PD-L1-decorated NETs, which may provide a new strategy for early detection and treatment of pulmonary metastasis in patients with breast cancer.
Poverty, race, ethnicity, and survival in pediatric nonmetastatic osteosarcoma: a Children’s Oncology Group report
Authors: Lenka Ilcisin, Ruxu Han, Mark Krailo, David S Shulman, Brent R Weil, Christopher B Weldon, Puja Umaretiya, Rahela Aziz-Bose, Katie A Greenzang, Richard Gorlick, Damon R Reed, R Lor Randall, Helen Nadel, Odion Binitie, Steven G Dubois, Katherine A Janeway, Kira Bona
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Children living in poverty and those of marginalized race or ethnicity experience inferior disease outcomes across many cancers. Whether survival disparities exist in osteosarcoma is poorly defined. We investigated the association between race, ethnicity, and proxied poverty exposures and event-free and overall survival for children with nonmetastatic osteosarcoma receiving care on a cooperative group trial. Methods We conducted a retrospective cohort study of US patients with nonmetastatic, osteosarcoma aged 5-21 years enrolled on the Children’s Oncology Group trial AOST0331. Race and ethnicity were categorized to reflect historically marginalized populations, as Hispanic, non-Hispanic Black, non-Hispanic Other, and non-Hispanic White. Poverty was proxied at the household and neighborhood levels. Overall survival and event-free survival functions of time from trial enrollment were estimated using the Kaplan–Meier method. Hypotheses of associations between risks for event-free survival, death, and postrelapse death with race and ethnicity were assessed using log-rank tests. Results Among 758 patients, 25.6% were household-poverty and 28.5% neighborhood-poverty exposed. Of the patients, 21% of children identified as Hispanic, 15.4% non-Hispanic Black, 5.3% non-Hispanic Other, and 54.0% non-Hispanic White. Neither household or neighborhood poverty nor race and ethnicity were statistically significantly associated with risks for event-free survival or death. Postrelapse risk for death differed statistically significantly across race and ethnicity with non-Hispanic Black patients at greatest risk (4-year postrelapse survival 35.7% Hispanic vs 13.0% non-Hispanic Black vs 43.8% non-Hispanic Other vs 38.9% non-Hispanic White; P = .0046). Conclusions Neither proxied poverty exposures or race and ethnicity were associated with event-free survival or overall survival, suggesting equitable outcomes following frontline osteosarcoma trial-delivered therapy. Non-Hispanic Black children experienced statistically significant inferior postrelapse survival. Investigation of mechanisms underlying postrelapse disparities are paramount.
Prevalence and Rapid Screen Method of Diagnostic Criteria for Psychosomatic Research Syndromes in Human Papillomavirus-Infected Patients
Authors: Xuelian Cui, Lixin Ding, Yongjuan Xu, Xiaosong Yuan, Qiaoli Zhang, Chiara Rafanelli, Sara Gostoli, Zhiwei Liu, Jianxin Cao
Journal: Psychotherapy and Psychosomatics (2024)

The early and rapid identification of psychosomatic symptoms is crucial to prevent harmful outcomes in patients with human papillomavirus (HPV) infection in busy comprehensive clinics. This study aimed to explore the prevalence and rapid screening method of the Diagnostic Criteria for Psychosomatic Research-revised (DCPR) syndromes in patients with HPV infection.
PHACTboost: A Phylogeny-aware Pathogenicity Predictor for the Missense Mutations via Boosting
Authors: Onur Dereli, Nurdan Kuru, Emrah Akkoyun, Aylin Bircan, Oznur Tastan, Ogün Adebali
Journal: Molecular Biology and Evolution (2024)

Most algorithms that are used to predict the effects of variants rely on evolutionary conservation. However, a majority of such techniques compute evolutionary conservation by solely using the alignment of multiple sequences while overlooking the evolutionary context of substitution events. We had introduced PHACT, a scoring-based pathogenicity predictor for missense mutations that can leverage phylogenetic trees, in our previous study. By building on this foundation, we now propose PHACTboost, a gradient boosting tree-based classifier that combines PHACT scores with information from multiple sequence alignments, phylogenetic trees, and ancestral reconstruction. By learning from data, PHACTboost outperforms PHACT. Furthermore, the results of comprehensive experiments on carefully constructed sets of variants demonstrated that PHACTboost can outperform 40 prevalent pathogenicity predictors reported in the dbNSFP, including conventional tools, metapredictors, and deep learning-based approaches as well as more recent tools such as AlphaMissense, EVE, and CPT-1. The superiority of PHACTboost over these methods was particularly evident in case of hard variants for which different pathogenicity predictors offered conflicting results. We provide predictions of 215 million amino acid alterations over 20,191 proteins. PHACTboost is available at https://github.com/CompGenomeLab/PHACTboost. PHACTboost can improve our understanding of genetic diseases and facilitate more accurate diagnoses.
Emotional Changes during Imagery Rescripting of Aversive Social Memories in Social Anxiety Disorder: A Randomized Controlled Trial
Authors: Rosa J Seinsche, Susanne Fricke, Marie K Neudert, Raphaela I Zimmer, Rudolf Stark, Andrea Hermann
Journal: Psychotherapy and Psychosomatics (2024)

Imagery rescripting (ImRs) is a psychotherapeutic intervention targeting aversive memories. During the three-phase intervention, patients reexperience their aversive memory (phase 1), observe the scene from their adult perspective, and intervene to help their former selves (phase 2), and reexperience it again with the positive changes (phase 3). Previous studies have rarely investigated emotional and regulatory processes taking place during the intervention.
Network Pharmacology as a Platform for Drug Discovery for Hypertrophic Scars
Authors: Jennifer Y Wang, Margaret Kabakova, Evan Austin, Jared Jagdeo
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Network Pharmacology as a Platform for Drug Discovery for Hypertrophic Scars Get access Jennifer Y Wang, Jennifer Y Wang Department of Dermatology, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA Search for other works by this author on: Oxford Academic Google Scholar Margaret Kabakova, Margaret Kabakova Department of Dermatology, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA Search for other works by this author on: Oxford Academic Google Scholar Evan Austin, Evan Austin Department of Dermatology, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA Search for other works by this author on: Oxford Academic Google Scholar Jared Jagdeo Jared Jagdeo Department of Dermatology, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA Corresponding Author: Jared Jagdeo MD, MS, Email:jrjagdeo@gmail.com https://orcid.org/0000-0002-7619-7650 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae272, https://doi.org/10.1093/bjd/ljae272 Published: 27 June 2024 Article history Received: 18 June 2024 Accepted: 25 June 2024 Published: 27 June 2024