tbuckley/cabot-search huggingface dataset:
Systolic Blood Pressure and Survival to Very Old Age: Results From the Women’s Health Initiative
Authors: Bernhard Haring, Chris A. Andrews, Kathleen Hovey, Aladdin H. Shadyab, Andrea LaCroix, Lisa Warsinger Martin, Milagros C. Rosal, Lewis H. Kuller, Elena Salmoirago-Blotcher, Nazmus Saquib, Patrick Koo, Deepika Laddu, Marcia L. Stefanick, JoAnn E. Manson, Sylvia Wassertheil-Smoller, Michael J. LaMonte
Journal: Circulation (2024)

The relationship between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine which SBP levels in women ≥65 years of age with or without blood pressure medication were associated with the highest probability of surviving to 90 years of age. The study population consisted of 16 570 participants enrolled in the Women's Health Initiative who were eligible to survive to 90 years of age by February 28, 2020, without a history of cardiovascular disease, diabetes, or cancer. Blood pressure was measured at baseline (1993 through 1998) and then annually through 2005. The outcome was defined as survival to 90 years of age with follow-up. Absolute probabilities of surviving to 90 years of age were estimated for all combinations of SBP and age using generalized additive logistic regression modeling. The SBP that maximized survival was estimated for each age, and a 95% CI was generated. During a median follow-up of 19.8 years, 9723 of 16 570 women (59%) survived to 90 years of age. Women with an SBP between 110 and 130 mm Hg at attained ages of 65, 70, 75, and 80 years had a 38% (95% CI, 34%-48%), 54% (52%-56%), 66% (64%-67%), or 75% (73%-78%) absolute probability to survive to 90 years of age, respectively. The probability of surviving to 90 years of age was lower for greater SBP levels. Women at the attained age of 80 years with 0%, 20%, 40%, 60%, 80%, or 100% time in therapeutic range (defined as an SBP between 110 and 130 mm Hg) had a 66% (64%-69%), 68% (67%-70%), 71% (69%-72%), 73% (71%-74%), 75% (72%-77%), or 77% (74%-79%) absolute survival probability to 90 years of age. For women >65 years of age with low cardiovascular disease and other chronic disease risk, an SBP level <130 mm Hg was found to be associated with longevity. These findings reinforce current guidelines targeting an SBP target <130 mm Hg in older women.
Immunoproteasomal Processing of IsoLG-Adducted Proteins Is Essential for Hypertension
Authors: Néstor de la Visitación, Wei Chen, Jaya Krishnan, Justin P. Van Beusecum, Venkataraman Amarnath, Elizabeth M. Hennen, Shilin Zhao, Mohammad Saleem, Mingfang Ao, Sergey I. Dikalov, Anna E. Dikalova, David G. Harrison, David M. Patrick
Journal: Circulation Research (2024)

Hypertension is characterized by CD8
The relationships between insomnia, nightmares, and dreams: A systematic review
Authors: Julia-Pizzamiglio Delage, Jeannie Côté, William-Girard Journault, Alexandre Lemyre, Célyne H. Bastien
Journal: Sleep Medicine Reviews (2024)

Insomnia and nightmares are both prevalent and debilitating sleep difficulties. The present systematic review aims to document the relationships between insomnia and nightmares in individuals without a concomitant psychopathology. The relationships between insomnia and dreams are also addressed. PsycINFO and Medline were searched for papers published in English or French from 1970 to March 2023. Sixty-seven articles were included for review. Most results support positive relationships between insomnia variables and nightmare variables in individuals with insomnia, individuals with nightmares, the general population, students, children and older adults, and military personnel and veterans. These positive relationships were also apparent in the context of the COVID-19 pandemic. Some psychological interventions, such as Imagery Rehearsal Therapy, might be effective in alleviating both nightmares and insomnia symptoms. Regarding the relationships between insomnia and dreams, compared with controls, the dreams of individuals with insomnia are characterized by more negative contents and affects. The results show that insomnia and nightmares are connected and may be mutually aggravating. A model is proposed to explain how insomnia might increase the likelihood of experiencing nightmares, and how nightmares can in turn lead to sleep loss and nonrestorative sleep.
Proteomic Analyses in Diverse Populations Improved Risk Prediction and Identified New Drug Targets for Type 2 Diabetes
Authors: Pang Yao, Andri Iona, Alfred Pozarickij, Saredo Said, Neil Wright, Kuang Lin, Iona Millwood, Hannah Fry, Christiana Kartsonaki, Mohsen Mazidi, Yiping Chen, Fiona Bragg, Bowen Liu, Ling Yang, Junxi Liu, Daniel Avery, Dan Schmidt, Dianjianyi Sun, Pei Pei, Jun Lv, Canqing Yu, Michael Hill, Derrick Bennett, Robin Walters, Liming Li, Robert Clarke, Huaidong Du, Zhengming Chen
Journal: Diabetes Care (2024)

Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D).
Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: A systematic review and meta-analysis
Authors: Harry Crane, Guy D. Eslick, Cameron Gofton, Anjiya Shaikh, George Cholankeril, Mark Cheah, Jian-Hong Zhong, Gianluca Svegliati-Baroni, Alessandro Vitale, Beom Kyung Kim, Sang Hoon Ahn, Mi Na Kim, Simone I Strasser, Jacob George
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD).Methods: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC.Results: 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC.Conclusions: MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.
Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic liver disease
Authors: Yiyuan Zheng, Lina Zhao, Zhekun Xiong, Chaoyuan Huang, Qiuhong Yong, Dan Fang, Yugang Fu, Simin Gu, Chong Chen, Jiacheng Li, Yingying Zhu, Jing Liu, Fengbin Liu, Yong Li
Journal: Clinical and Molecular Hepatology (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.
Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake
Authors: Yawen Cheng, Yuan Zhu, Yaoshan Liu, Xuenan Liu, Yanan Ding, Deli Li, Xiao Zhang, Yunsong Liu
Journal: International Journal of Oral Science (2024)

Abstract Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.
Characterizing glucokinase variant mechanisms using a multiplexed abundance assay
Authors: Sarah Gersing, Thea K. Schulze, Matteo Cagiada, Amelie Stein, Frederick P. Roth, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Journal: Genome biology (2024)

Abstract Background Amino acid substitutions can perturb protein activity in multiple ways. Understanding their mechanistic basis may pinpoint how residues contribute to protein function. Here, we characterize the mechanisms underlying variant effects in human glucokinase (GCK) variants, building on our previous comprehensive study on GCK variant activity. Results Using a yeast growth-based assay, we score the abundance of 95% of GCK missense and nonsense variants. When combining the abundance scores with our previously determined activity scores, we find that 43% of hypoactive variants also decrease cellular protein abundance. The low-abundance variants are enriched in the large domain, while residues in the small domain are tolerant to mutations with respect to abundance. Instead, many variants in the small domain perturb GCK conformational dynamics which are essential for appropriate activity. Conclusions In this study, we identify residues important for GCK metabolic stability and conformational dynamics. These residues could be targeted to modulate GCK activity, and thereby affect glucose homeostasis.
Ruxolitinib Cream 1.5%: A Review in Non-Segmental Vitiligo
Authors: Connie Kang
Journal: Drugs (2024)

Topical ruxolitinib 1.5% cream (Opzelura®), a Janus kinase (JAK) inhibitor, is the first treatment to be approved in several countries for use in patients aged ≥ 12 years with non-segmental vitiligo. In the identical phase III TRuE-V1 and TRuE-V2 trials, significantly more ruxolitinib cream recipients were able to achieve statistically significant and clinically meaningful facial and total body repigmentation, as well as reductions in vitiligo noticeability, compared with vehicle recipients. Efficacy was sustained in longer-term analyses to week 104 of treatment. Ruxolitinib 1.5% cream was generally tolerable in these trials; the most common treatment-related adverse events were acne, pruritus and exfoliation, all at the application site. As with orally administered JAK inhibitors, topical ruxolitinib carries boxed warnings in the USA for serious infections, mortality, malignancy, major adverse cardiovascular events (MACE) and thrombosis, although the incidences were low with topical application. Thus, topical ruxolitinib 1.5% cream is an effective and generally tolerable treatment option for patients aged ≥ 12 years with non-segmental vitiligo. Non-segmental vitiligo is a chronic autoimmune disease where the skin throughout the body loses its pigmentation, and is usually managed with topical therapies, light therapy or surgery. Topical ruxolitinib 1.5% cream (Opzelura®) is the first treatment approved in several countries for patients aged ≥ 12 years with non-segmental vitiligo. It inhibits Janus kinase (JAK) proteins, reducing the destruction of skin pigment-producing cells. In two clinical trials, significantly more ruxolitinib cream recipients achieved significant and meaningful skin repigmentation compared with patients who received a non-medicated cream; these results were sustained to week 104 of treatment. Ruxolitinib 1.5% cream was generally tolerable; the most common treatment-related adverse events were acne, itchiness and exfoliation, all at the application site. Topical ruxolitinib has special warnings in the USA for major adverse cardiovascular events (MACE), blood clots, serious infections, death and cancer (associated with the use of oral JAK inhibitors), although incidence rates for these adverse events were low in the clinical trials. Topical ruxolitinib 1.5% cream is an effective and generally tolerable treatment option for patients aged ≥ 12 years with non-segmental vitiligo.
Making a virtue out of an evil: Are red blood cells from chronic mountain sickness patients eligible for transfusions?
Authors: Emeric Stauffer, Aurélien P. Pichon, Benoit Champigneulle, Michaël Furian, Ivan Hancco, Alexis Darras, Paul Robach, Julien V. Brugniaux, Elie Nader, Philippe Connes, Samuel Verges, Lars Kaestner
Journal: American Journal of Hematology (2024)

We investigated highlanders, permanently living at an altitude of 5100 m and compared Chronic Mountain Sickness (CMS) patients with control volunteers. While we found differences in systemic parameters such as blood oxygen content, hematocrit, hemoglobin concentration, and blood viscosity, the mechanical and rheological properties of single red blood cells did not differ between the two investigated groups.
Cuproptosis: Advances in Stimulus‐Responsive Nanomaterials for Cancer Therapy
Authors: Jiacheng Lu, Yuqing Miao, Yuhao Li
Journal: Advanced Healthcare Materials (2024)

Abstract Cuproptosis, a recently identified non‐apoptotic programmed cell death modality, attracts considerable attention in the realm of cancer therapeutics owing to its unique cellular demise mechanisms. Since its initial report in 2022, strategies inducing or amplifying cuproptosis for cancer treatment emerge. The engineering of nano‐systems to elicit cuproptosis effectively circumvents constraints associated with conventional small‐molecule pharmaceutical interventions, presenting novel prospects for oncological therapy. Stimulus‐responsive nanomaterials, leveraging their distinctive spatiotemporal control attributes, are investigated for their role in modulating the induction or augmentation of cuproptosis. In this comprehensive review, the physiological characteristics of cuproptosis, encompassing facets such as copper overload and depletion, coupled with regulatory factors intrinsic to cuproptosis, are expounded upon. Subsequently, design methodologies for stimulus‐responsive induction or enhancement of cuproptosis, employing stimuli such as light, ultrasound, X‐ray, and the tumor microenvironment, are systematically delineated. This review encompasses intricacies in nanomaterial design, insights into the therapeutic processes, and the associated advantages. Finally, challenges inherent in stimulus‐responsive induction/enhancement of cuproptosis are deliberated upon and prospective insights into the future trajectory of copper‐mediated cancer therapy are provided.
Active learning using adaptable task-based prioritisation
Authors: Shaheer U. Saeed, João Ramalhinho, Mark Pinnock, Ziyi Shen, Yunguan Fu, Nina Montaña-Brown, Ester Bonmati, Dean C. Barratt, Stephen P. Pereira, Brian Davidson, Matthew J. Clarkson, Yipeng Hu
Journal: Medical Image Analysis (2024)

Supervised machine learning-based medical image computing applications necessitate expert label curation, while unlabelled image data might be relatively abundant. Active learning methods aim to prioritise a subset of available image data for expert annotation, for label-efficient model training. We develop a controller neural network that measures priority of images in a sequence of batches, as in batch-mode active learning, for multi-class segmentation tasks. The controller is optimised by rewarding positive task-specific performance gain, within a Markov decision process (MDP) environment that also optimises the task predictor. In this work, the task predictor is a segmentation network. A meta-reinforcement learning algorithm is proposed with multiple MDPs, such that the pre-trained controller can be adapted to a new MDP that contains data from different institutes and/or requires segmentation of different organs or structures within the abdomen. We present experimental results using multiple CT datasets from more than one thousand patients, with segmentation tasks of nine different abdominal organs, to demonstrate the efficacy of the learnt prioritisation controller function and its cross-institute and cross-organ adaptability. We show that the proposed adaptable prioritisation metric yields converging segmentation accuracy for a new kidney segmentation task, unseen in training, using between approximately 40% to 60% of labels otherwise required with other heuristic or random prioritisation metrics. For clinical datasets of limited size, the proposed adaptable prioritisation offers a performance improvement of 22.6% and 10.2% in Dice score, for tasks of kidney and liver vessel segmentation, respectively, compared to random prioritisation and alternative active sampling strategies.
TCTAP C-082 Out With the Old, in With the New: Previous Stent Rotablation With Intravascular Lithotripsy
Authors: Mohd Asyiq Al-Fard Bin Mohd Raffali, Boon Cong Beh, Noor Diyana binti Mohamad Farouk, Shawal Faizal Mohamad, Muhamad Ali SK Abdul Kader, Hamat Hamdi Che Hassan
Journal: Journal of the American College of Cardiology (2024)
TCTAP C-032 Against All Odds
Authors: Liew Kai Soon, Vijayendran Rajalingam, Yuen Hoong Phang, Kenneth Kay Leong Khoo, Huan Yean Kang, Aditya Fahmi Prianda, Chai Yih Tan, Kantha Rao Narasamuloo, Saravanan Krishinan, Chee Tat Liew, Dharmaraj Karthikesan
Journal: Journal of the American College of Cardiology (2024)
TCTAP C-076 An Imaging Guided Percutaneous Intervention to Ostial Chronic Total Occlusion of Left Anterior Descending Artery
Authors: Chai Yih Tan, Kai Soon Liew, Huan Yean Kang, Aditya Fahmi Prianda, Yuen Hoong Phang, Kenneth Kay Leong Khoo, Kantha Rao Narasamuloo, Saravanan Krishinan, Chee Tat Liew, Dharmaraj Karthikesan
Journal: Journal of the American College of Cardiology (2024)
TCTAP A-047 Outcomes of Mechanical Ventilation in Patients With Cardiogenic Shock Requiring Intra-Aortic Balloon Pump: A 10-Year Retrospective Data Review
Authors: Khaled Al Khodari, Alaa Rahhal, Mohammed Awad Ashour, Raad Tahtouh, Eman Shehada, Wael Kanjo, Abdelaziz M. Tawengi, Mohamed Mahmoud Tawengi, Mohamad Fael, Nourelhuda Issa, Abdul Rahman Arabi
Journal: Journal of the American College of Cardiology (2024)
TCTAP C-210 Patient-Specific Computer Simulation of Virtual Balloon Pre-dilatation and Accurate Assessment of a High-Risk Patient Before Transcatheter Aortic Valve Replacement
Authors: Xinlei Wu, Zhu Jinyun, Xing Liu, YiQiu Jiang, Yongfang Liu, Daozhu Wu, Xinmin Zhang, Lianpin Wu
Journal: Journal of the American College of Cardiology (2024)
TCTAP A-033 Impact of Postprocedural Percent Diameter Stenosis of 30 on Cumulative 3-Year Cardiovascular Outcomes After Elective Drug-Coated Balloon Angioplasty to de Novo Coronary Stenosis
Authors: Yohei Tamura, Tetsuya Ishikawa, Kota Yamada, Tomoaki Ukaj, Yuki Kondo, Masatoshi Shimura, Taro Takeyama, Kahoko Mori, Arai Miona, Jun Usami, Yoshihiro Mera, Itaru Hisauchi, Shiro Nakahara, Yuji Itabashi, Sayuki Kobayash, Yoshihiko Sakai, Isao Taguchi
Journal: Journal of the American College of Cardiology (2024)
Unique Interplay Between Antinuclear Antibodies and Nuclear Molecules in the Pathogenesis of Systemic Lupus Erythematosus
Authors: David S. Pisetsky
Journal: Arthritis & Rheumatology (2024)

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that primarily affects young women and causes a wide range of inflammatory manifestations. The hallmark of SLE is the production of antibodies to components of the cell nucleus (antinuclear antibodies [ANAs]). These antibodies can bind to DNA, RNA, and protein complexes with nucleic acids. Among ANAs, antibodies to DNA (anti-DNA) are markers for classification and disease activity, waxing and waning disease activity in many patients. In the blood, anti-DNA antibodies can bind to DNA to form immune complexes with two distinct roles in pathogenesis: (1) renal deposition to provoke nephritis and (2) stimulation of cytokine production following uptake into innate immune cells and interaction with internal nucleic acid sensors. These sensors are part of an internal host defense system in the cell cytoplasm that can respond to DNA from infecting organisms; during cell stress, DNA from nuclear and mitochondrial sources can also trigger these sensors. The formation of immune complexes requires a source of extracellular DNA in an immunologically accessible form. As shown in in vivo and in vitro systems, extracellular DNA can emerge from dead and dying cells in both a free and a particulate form. Neutrophils undergoing the process of NETosis can release DNA in mesh-like structures called neutrophil extracellular traps. In SLE, therefore, the combination of ANAs and immunologically active DNA can create new structures that can promote inflammation throughout the body as well as drive organ inflammation and damage.
TCTAP C-042 A Challenging Case of Calcified Chronic Total Occlusion Lesion in Multivessel Coronary Angioplasty
Authors: Hisham Shahrom, Huzairi Sani, Ing Xiang Pang, Abdul Ariff, Ahmad Faisal Badaruddin, Shaiful Azmi Yahaya
Journal: Journal of the American College of Cardiology (2024)