tbuckley/cabot-search huggingface dataset:
Meet the First Authors
Authors: An-Jing Ren, Sneha Raju, Kathryn Howe
Journal: Circulation Research (2024)

in China.His MS and PhD areas of expertise are physiology, and his postdoctoral research focused on pathophysiology.This work is a continuation of the previous study on cardiac dysfunction following ZBTB20 global knockout.His main research area is the pathogenesis of cardiovascular diseases.The biggest realization he had in this research is that no matter how many difficulties one encounters, as long as you persist, you will definitely achieve success.
Mechanism of Ventricular Tachycardia Occurring in Chronic Myocardial Infarction Scar
Authors: J. Kevin Donahue, Jonathan Chrispin, Olujimi A. Ajijola
Journal: Circulation Research (2024)

Cardiac arrest is the leading cause of death in the more economically developed countries. Ventricular tachycardia associated with myocardial infarct is a prominent cause of cardiac arrest. Ventricular arrhythmias occur in 3 phases of infarction: during the ischemic event, during the healing phase, and after the scar matures. Mechanisms of arrhythmias in these phases are distinct. This review focuses on arrhythmia mechanisms for ventricular tachycardia in mature myocardial scar. Available data have shown that postinfarct ventricular tachycardia is a reentrant arrhythmia occurring in circuits found in the surviving myocardial strands that traverse the scar. Electrical conduction follows a zigzag course through that area. Conduction velocity is impaired by decreased gap junction density and impaired myocyte excitability. Enhanced sympathetic tone decreases action potential duration and increases sarcoplasmic reticular calcium leak and triggered activity. These elements of the ventricular tachycardia mechanism are found diffusely throughout scar. A distinct myocyte repolarization pattern is unique to the ventricular tachycardia circuit, setting up conditions for classical reentry. Our understanding of ventricular tachycardia mechanisms continues to evolve as new data become available. The ultimate use of this information would be the development of novel diagnostics and therapeutics to reliably identify at-risk patients and prevent their ventricular arrhythmias.
Impact of micronutrients and nutraceuticals on cognitive function and performance in Alzheimer's disease
Authors: Lorenza Guarnieri, Francesca Bosco, Antonio Leo, Rita Citraro, Ernesto Palma, Giovambattista De Sarro, Vincenzo Mollace
Journal: Ageing Research Reviews (2024)

Alzheimer's disease (AD) is a major global health problem today and is the most common form of dementia. AD is characterized by the formation of β-amyloid (Aβ) plaques and neurofibrillary clusters, leading to decreased brain acetylcholine levels in the brain. Another mechanism underlying the pathogenesis of AD is the abnormal phosphorylation of tau protein that accumulates at the level of neurofibrillary aggregates, and the areas most affected by this pathological process are usually the cholinergic neurons in cortical, subcortical, and hippocampal areas. These effects result in decreased cognitive function, brain atrophy, and neuronal death. Malnutrition and weight loss are the most frequent manifestations of AD, and these are also associated with greater cognitive decline. Several studies have confirmed that a balanced low-calorie diet and proper nutritional intake may be considered important factors in counteracting or slowing the progression of AD, whereas a high-fat or hypercholesterolemic diet predisposes to an increased risk of developing AD. Especially, fruits, vegetables, antioxidants, vitamins, polyunsaturated fatty acids, and micronutrients supplementation exert positive effects on aging-related changes in the brain due to their antioxidant, anti-inflammatory, and radical scavenging properties. The purpose of this review is to summarize some possible nutritional factors that may contribute to the progression or prevention of AD, understand the role that nutrition plays in the formation of Aβ plaques typical of this neurodegenerative disease, to identify some potential therapeutic strategies that may involve some natural compounds, in delaying the progression of the disease.
Cytogenetic and Molecular Associations with Outcomes in Higher-Risk Myelodysplastic Syndromes Treated with Hypomethylating Agents plus Venetoclax
Authors: Alexandre Bazinet, Sai Prasad Desikan, Ziyi Li, Juan Jose Rodriguez-Sevilla, Sangeetha Venugopal, Samuel Urrutia, Guillermo Montalban-Bravo, Koji Sasaki, Kelly S. Chien, Danielle Hammond, Rashmi Kanagal-Shamanna, Irene Ganan-Gomez, Tapan M. Kadia, Gautam Borthakur, Courtney D. DiNardo, Naval G. Daver, Elias J. Jabbour, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated with outcomes with this combination for HR-MDS are incompletely understood. Experimental Design: We pooled patient data from 3 prospective trials evaluating HMA–venetoclax in HR-MDS to study associations between cytogenetic and molecular factors and overall response rate (ORR), overall survival (OS), and event-free survival (EFS). The Kaplan–Meier method was used to estimate time-to-event endpoints. Univariate and multivariate analyses using logistic regression (for ORR) or the Cox proportional hazards model (for OS and EFS) were used to identify associations between clinical, cytogenetic, and molecular factors and outcomes. Results: A total of 80 patients (52 HMA-naïve, 28 HMA-failure) were included. ORR was 90% in HMA-naïve and 57% in HMA-failure. Median OS was 28.2 and 8.3 months in HMA-naïve and HMA-failure, respectively. Median EFS was 17.9 and 5.5 months in HMA-naïve and HMA-failure, respectively. In addition, 24/52 (46%) of the HMA-naïve and 3/28 (11%) of the HMA-failure patients proceeded to allogeneic stem cell transplantation (SCT). Factors associated with inferior outcomes were prior HMA failure, complex cytogenetics, trisomy 8, TP53 mutations, and RAS pathway mutations. Mutations in RNA splicing, DNA methylation, and ASXL1 appeared favorable. Blast percentage was not predictive of outcomes. Conclusions: Knowledge of cytogenetic and molecular alterations may help identify which patients with HR-MDS benefit the most from venetoclax.
Improving Community Care of Individuals with CKD
Authors: Cynthia Ciwei Lim, Wei Yi Tay
Journal: Journal of the American Society of Nephrology (2024)

1Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore 2Population Health and Integrated Care Office, SingHealth, Singapore, Singapore 3Family Medicine Continuing Care, Singapore General Hospital, Singapore, Singapore Correspondence: Dr. Cynthia Ciwei Lim, Department of Renal Medicine, Singapore General Hospital. Academia Level 3, 20 College Road. Singapore 169856. Email: [email protected] Published online ahead of print. Publication date available at www.jasn.org. See original article, "Proceedings of a Workshop to Promote Community Health Worker Interventions in Nephrology," in Vol. 34, Iss. 11, 1812–1818.
The D84G mutation in STIM1 causes nuclear envelope dysfunction and myopathy in mice
Authors: Victoria Bryson, Chaojian Wang, Zirui Zhou, Kavisha Singh, Noah Volin, Eda Yildirim, Paul Rosenberg
Journal: Journal of Clinical Investigation (2024)

Stromal interaction molecule 1 (STIM1) is a Ca2+ sensor located in the sarcoplasmic reticulum (SR) of skeletal muscle where it is best known for its role in store operated Ca2+ entry (SOCE). Genetic syndromes resulting from STIM1 mutations are recognized as a cause of muscle weakness and atrophy. Here, we focus on a gain of function mutation that occurs in humans and mice (STIM1+/D84G mice) where muscles exhibit constitutive SOCE. Unexpectedly, this constitutive SOCE did not affect global Ca2+ transients, SR Ca2+ content or excitation contraction coupling (ECC) and was therefore unlikely to underlie the reduced muscle mass and weakness observed in these mice. Instead, we demonstrate that the presence of D84G STIM1 in the nuclear envelope disrupts nuclear-cytosolic coupling causing severe derangement in nuclear architecture of STIM1+/D84G muscle, DNA damage and altered lamina A associated gene expression. Functionally, we found D84G STIM1 reduced the transfer of Ca2+ from the cytosol to the nucleus in myoblasts resulting in a reduction of [Ca2+]N. Taken together, we propose a novel role for STIM1 in the nuclear envelope that links Ca2+ signaling to nuclear stability in skeletal muscle.
HER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial
Authors: Zheqi Li, Otto Metzger Filho, Giuseppe Viale, Patrizia dell’Orto, Leila Russo, Marie-Anne Goyette, Avni Kamat, Denise A. Yardley, Vandana Gupta Abramson, Carlos L. Arteaga, Laura M. Spring, Kami Chiotti, Carol Halsey, Adrienne G. Waks, Tari A. King, Susan C. Lester, Jennifer R. Bellon, Eric P. Winer, Paul T. Spellman, Ian E. Krop, Kornelia Polyak
Journal: Journal of Clinical Investigation (2024)

BACKGROUNDHER2-targeting therapies have great efficacy in HER2-positive breast cancer, but resistance, in part due to HER2 heterogeneity (HET), is a significant clinical challenge. We previously described that in a phase II neoadjuvant trastuzumab emtansine (T-DM1) and pertuzumab (P) clinical trial in early-stage HER2-positive breast cancer, none of the patients with HER2-HET tumors had pathologic complete response (pCR).METHODSTo investigate cellular and molecular differences among tumors according to HER2 heterogeneity and pCR, we performed RNA sequencing and ERBB2 FISH of 285 pretreatment and posttreatment tumors from 129 patients in this T-DM1+P neoadjuvant trial. A subset of cases was also subject to NanoString spatial digital profiling.RESULTSPretreatment tumors from patients with pCR had the highest level of ERBB2 mRNA and ERBB signaling. HER2 heterogeneity was associated with no pCR, basal-like features, and low ERBB2 expression yet high ERBB signaling sustained by activation of downstream pathway components. Residual tumors showed decreased HER2 protein levels and ERBB2 copy number heterogeneity and increased PI3K pathway enrichment and luminal features. HET tumors showed minimal treatment-induced transcriptomic changes compared with non-HET tumors. Immune infiltration correlated with pCR and HER2-HET status.CONCLUSIONResistance mechanisms in HET and non-HET tumors are distinct. HER2-targeting antibodies have limited efficacy in HET tumors. Our results support the stratification of patients based on HET status and the use of agents that target downstream components of the ERBB signaling pathway in patients with HET tumors.TRIAL REGISTRATIONClinicalTrials.gov NCT02326974.FUNDINGThis study was funded by Roche and the National Cancer Institute.
Combining Genomic Biomarkers to Guide Immunotherapy in Non–Small Cell Lung Cancer
Authors: Joris van de Haar, Joanne M. Mankor, Karlijn Hummelink, Kim Monkhorst, Egbert F. Smit, Lodewyk F.A. Wessels, Edwin Cuppen, Joachim G.J.V. Aerts, Emile E. Voest
Journal: Clinical Cancer Research (2024)

The clinical value of STK11, KEAP1, and EGFR alterations for guiding immune checkpoint blockade (ICB) therapy in non-small cell lung cancer (NSCLC) remains controversial, as some patients with these proposed resistance biomarkers show durable ICB responses. More specific combinatorial biomarker approaches are urgently needed for this disease.
Post-cardiac arrest temporal evolution of left ventricular function in a rat model: speckle-tracking echocardiography and cardiac circulating biomarkers
Authors: Daria De Giorgio, Davide Olivari, Francesca Fumagalli, Deborah Novelli, Marianna Cerrato, Francesca Motta, Giuseppe Ristagno, Roberto Latini, Lidia Staszewsky
Journal:  (2024)

Abstract Aims There is little information from experimental studies regarding the evolution of post-resuscitation cardiac arrest [post-return of spontaneous circulation (post-ROSC)] myocardial dysfunction during mid-term follow-up. For this purpose, we assessed left ventricular (LV) function and circulating cardiac biomarkers at different time points in a rat model of cardiac arrest (CA). Methods and results Rats were divided into two groups: control and post-ROSC rats. Eight minutes of untreated ventricular fibrillation were followed by 8 min of cardiopulmonary resuscitation. Conventional and speckle-tracking echocardiographic (STE) parameters and cardiac circulating biomarkers concentrations were assessed, at 3, 4, 72, and 96 h post-ROSC. At 3 and 4 h post-ROSC, LV systolic function was severely impaired, and high-sensitivity cardiac troponin T and N-terminal pro-atrial natriuretic peptide (NT-proANP) plasma concentrations were significantly increased, compared with control rats (P &amp;lt; 0.0001 for all). At 72 and 96 h post-ROSC, LV ejection fraction (LVEF) normalized. At 96 h, the following variables were significantly different from control rats: early trans-mitral peak velocity, 56.8 ± 3.1 vs. 87.8 ± 3.8 cm/s, P &amp;lt; 0.0001; late trans-mitral peak velocity, 50.6 ± 4.7 vs. 73.7 ± 4.2 cm/s, P &amp;lt; 0.0001; mean s′ wave velocity, 4.6 ± 0.3 vs. 5.9 ± 0.3 cm/s, P &amp;lt; 0.0001, global longitudinal strain (GLS) −7.5 ± 0.5 and vs. −11 ± 1.2%, P &amp;lt; 0.01; GLS rate (GLSR) −0.9 ± 0.4 and −2.3 ± 0.2 1/s, P &amp;lt; 0.01; and NT-proANP concentration, 2.5 (0.2; 6.0) vs. 0.4 (0.01; 1.0) nmol/L, P &amp;lt; 0.01. Conclusion s′ velocity, GLS, and GLSR indicated that LV systolic function was still impaired 96 h post-ROSC. These findings agree with NT-proANP concentrations, which continue to be high. Normalization of LVEF supports the use of STE for its greater sensitivity for monitoring post-CA cardiac function. Further investigations are needed to provide evidence of the post-ROSC LV diastolic function pattern.
Outcomes of cutaneous surgery for nonmelanoma skin cancer in patients with different Fitzpatrick skin types: A nationwide, multicenter, prospective study
Authors: Umer Nadir, Michael D. Yi, Eric Koza, Victoria J. Shi, Loma Dave, Farhana Ikmal Hisham, Amanda Maisel-Campbell, Katherine A. Lin, Sarah A. Ibrahim, Bianca Y. Kang, Noor Anvery, McKenzie A. Dirr, Rachel E. Christensen, Julia M. Riley, Roopal V. Kundu, Juliet L. Aylward, Omar Bari, Hamza Bhatti, Diana Bolotin, Basil S. Cherpelis, Joel L. Cohen, Sean Condon, Sheila Farhang, Bahar Firoz, Algin B. Garrett, Roy G. Geronemus, Nicholas J. Golda, Tatyana R. Humphreys, Eva A. Hurst, Oren H. Jacobson, Shang Brian Jiang, Pritesh S. Karia, Arash Kimyai-Asadi, David J. Kouba, Martha Laurin Council, Marilyn Le, Deborah F. MacFarlane, Ian A. Maher, Stanley J. Miller, Eduardo K. Moioli, Meghan Morrow, Julia Neckman, Samuel R. Peterson, Christine Poblete-Lopez, Chad L. Prather, Jennifer S. Ranario, Ashley G. Rubin, Andrew M. Swanson, Christopher Urban, Yaohui (Gloria) Xu, Ross Pearlman, Brian A. Cahn, Simon Yoo, Vishnu Harikumar, Alexandra Weil, Matthew Schaeffer, Sanjana Iyengar, Emily Poon, Murad Alam
Journal: Journal of the American Academy of Dermatology (2024)
Association of Cutaneous Keloids, Hypertrophic Scarring, and Fibrosis with Risk of Postoperative Proliferative Vitreoretinopathy
Authors: Danny A. Mammo, Karen Wai, Ehsan Rahimy, Carolyn K. Pan, Sunil K. Srivastava, Prithvi Mruthyunjaya
Journal: Ophthalmology (2024)

PurposeTo assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) with risk of post-operative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair.DesignRetrospective population-based cohort studyParticipantsPatients ≥ 18 years who underwent initial RD repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology (CPT) 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003 – March 1, 2023.MethodsA de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Statistical Classification of Diseases (ICD)-10 codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2), and CPT codes for secondary surgery including complex RD repair (67113) was determined. Proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) patients were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) was used to match for age, sex, and race.Main outcome measuresPrevalence of H35.2 and CPT 67113 within 180 days after RRD repair in KHF cohort versus non-KHF cohort.ResultsAmong patients with CPT 67108, 1,061 patients in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (SD) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (p=0.00, OR 3.2; 95% CI, 2.13-4.71). 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (p=0.008; OR 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF vs non-KHF cohort (9.0% vs 4.2%, p < 0.01; OR 2.28 (1.64-3.16).ConclusionA dermatologic history of keloids, hypertrophic scarring, or fibrosis may be a risk factor for proliferative vitreoretinopathy after retinal detachment repair.
Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry
Authors: Charlotte Durrington, Judith A. Hurdman, Charlie A. Elliot, Rhona Maclean, Joost Van Veen, Giorgia Saccullo, Duneesha De-Foneska, Andrew J. Swift, Rajaram Smitha, Catherine Hill, Steven Thomas, Krit Dwivedi, Samer Alabed, James M. Wild, Athanasios Charalampopoulos, Abdul Hameed, Alexander M.K. Rothman, Lisa Watson, Neil Hamilton, A.A. Roger Thompson, Robin Condliffe, David G. Kiely
Journal: European Respiratory Journal (2024)

Background Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined. Methods Over a 10-year period (2010–2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15–20 million) were included. Results Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p&lt;0.01), better exercise capacity (p&lt;0.05) and less severe pulmonary haemodynamics (p&lt;0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11–11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9–5.2 and 1.7–2.3 per million per year, respectively, for non-Sheffield residents. Conclusions In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH.
Cystic fibrosis in Europe: improved lung function and longevity – reasons for cautious optimism, but challenges remain
Authors: Eitan Kerem, Annalisa Orenti, Arianna Adamoli, Elpis Hatziagorou, Lutz Naehrlich, Isabelle Sermet-Gaudelus
Journal: European Respiratory Journal (2024)

Prognosis and disease severity in cystic fibrosis (CF) are linked to declining lung function. To characterise lung function by the number of adults in countries with different levels of Gross National Income (GNI), data from the European Cystic Fibrosis Society Patient Registry were utilised.
Physical Activity and Cognitive Decline Among Older Adults
Authors: Paula Iso-Markku, Sari Aaltonen, Urho M. Kujala, Hanna-Leena Halme, Daniel Phipps, Keegan Knittle, Eero Vuoksimaa, Katja Waller
Journal: JAMA Network Open (2024)

Importance Physical activity is associated with the risk for cognitive decline, but much of the evidence in this domain comes from studies with short follow-ups, which is prone to reverse causation bias. Objective To examine how length of follow-up, baseline age, physical activity amount, and study quality modify the longitudinal associations of physical activity with cognition. Data Sources Observational studies of adults with a prospective follow-up of at least 1 year, a valid baseline cognitive measure or midlife cohort, and an estimate of the association of baseline physical activity and follow-up cognition were sought from PsycInfo, Scopus, CINAHL, Web of Science, SPORTDiscus, and PubMed, with the final search conducted on November 2, 2022. Study Selection Two independent researchers screened titles with abstracts and full-text reports. Data Extraction and Synthesis Two reviewers independently assessed study quality and extracted data. Pooled estimates of association were calculated with random-effects meta-analyses. An extensive set of moderators, funnel plots, and scatter plots of physical activity amount were examined. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures Pooled estimates of the associations between physical activity and global cognition, as well as specific cognitive domains, were examined. Results A total of 104 studies with 341 471 participants were assessed. Analysis of binary outcomes included 45 studies with 102 452 individuals, analysis of follow-up global cognition included 14 studies with 41 045 individuals, and analysis of change in global cognition included 25 studies with 67 463 individuals. Physical activity was associated with a decreased incidence of cognitive impairment or decline after correction for funnel plot asymmetry (pooled risk ratio, 0.97; 95% CI, 0.97-0.99), but there was no significant association in follow-ups longer than 10 years. Physical activity was associated with follow-up global cognition (standardized regression coefficient, 0.03; 95% CI, 0.02-0.03) and change in global cognition (standardized regression coefficient, 0.01; 95% CI, 0.01 to 0.02) from trim-and-fill analyses, with no clear dose-response or moderation by follow-up length, baseline age, study quality or adjustment for baseline cognition. The specific cognitive domains associated with physical activity were episodic memory (standardized regression coefficient, 0.03; 95% CI, 0.02-0.04) and verbal fluency (standardized regression coefficient, 0.05; 95% CI, 0.03-0.08). Conclusions and Relevance In this meta-analysis of the association of physical activity with cognitive decline, physical activity was associated with better late-life cognition, but the association was weak. However, even a weak association is important from a population health perspective.