tbuckley/cabot-search huggingface dataset:
The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score–Matched Study
Authors: Zilin Zhuang, Ailifeire Yilihamu, Zhihua Li, Rong Lei, Xun Li, Mengjia Han, Wei Wei, Guangxin Li, Zhen Ma, Yulu Zhang, Hui Hu, Xiaoyun Xiao, Yan Nie
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. Patients and Methods: Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence–free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. Results: We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS ( P =.501) or OS ( P =.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS ( P =.934) or 5-year OS ( P =.328). Conclusions: According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.
Effect of antihypertensive deprescribing on hospitalisation and mortality: long-term follow-up of the OPTiMISE randomised controlled trial
Authors: James P Sheppard, Eleanor Temple, Ariel Wang, Anne Smith, Stephanie Pollock, Gary A Ford, F D Richard Hobbs, Nicola Kenealy, Paul Little, Mark Lown, Simon de Lusignan, Jonathan Mant, David McCartney, Rupert A Payne, Marney Williams, Ly-Mee Yu, Richard J McManus
Journal: The Lancet Healthy Longevity (2024)

Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. The OPTiMISE trial showed that this deprescribing can be achieved with no differences in blood pressure control at 3 months compared with usual care. We aimed to examine effects of deprescribing on longer-term hospitalisation and mortality.
The results reported by Van de Schootbrugge-Vandermeer et al. might not support their conclusions
Authors: Pernille T. Larsen, Susanne F. Jørgensen, Sisse H. Njor
Journal: Endoscopy (2024)

Letter to: Interval post-colonoscopy colorectal cancer following a negative colonoscopy in a fecal immunochemical test-based screening programEndoscopy 2023; 55(12): 1061-1069DOI: 10.1055/a-2136-6564
Update on SickleInAfrica: a collaborative and multidimensional approach to conduct research and improve health
Authors: Siana Nkya, Upendo Masamu, Patience Kuona, Sarah Kiguli, Aldiouma Guindo, Fred Stephen Sarfo, Obiageli Nnodu, Ambroise Wonkam, Emmanuel Balandya, Julie Makani
Journal: The Lancet Haematology (2024)
Response to Larsen et al.
Authors: Hilliene J. van de Schootbrugge-Vandermeer, Arthur Kooyker, Esther Toes-Zoutendijk, Manon C.W. Spaander, Monique E van Leerdam
Journal: Endoscopy (2024)

Letter to: The results reported by Van de Schootbrugge-Vandermeer et al. might not support their conclusionsEndoscopy 2024; 56(08): 635-635DOI: 10.1055/a-2271-2035
ESGE and Education in Endoscopy
Authors: Marianna Arvanitakis, Istvan Hritz
Journal: Endoscopy (2024)

Organizing, offering, and promoting educational activities aiming to provide knowledge, enhance skills and improve the quality of gastrointestinal endoscopy has been one of the cornerstones of the ESGE. The Education Committee was one of the first committees to be established in 1996. The position of Chair has been held by a series of endoscopists that share a passion regarding education, including Andrzej Nowak (Poland, 1996–2000), Aksel Kruse (Denmark, 2000–2004), Lars Aabbaken (Norway, 2004–2008), Istvan Racz (Hungary, 2008–2010), Mario Dinis-Ribeiro (Portugal, 2010–2014), Tomas Hucl (Czech Republic, 2014–2018), Marianna Arvanitakis (Belgium, 2018–2022) and currently Istvan Hritz (Hungary, 2022–2026).
Astrocyte reactivity is associated with tau tangle load and cortical thinning in Alzheimer’s disease
Authors: Tengfei Guo, Anqi Li, Pan Sun, Zhengbo He, Yue Cai, Guoyu Lan, Lin Liu, Jieyin Li, Jie Yang, Yalin Zhu, Ruiyue Zhao, Xuhui Chen, Dai Shi, Zhen Liu, Qingyong Wang, Linsen Xu, Liemin Zhou, Pengcheng Ran, Xinlu Wang, Kun Sun, Jie Lu, Ying Han
Journal: Molecular Neurodegeneration (2024)

Abstract Background It is not fully established whether plasma β-amyloid(Aβ) 42 /Aβ 40 and phosphorylated Tau 181 (p-Tau 181 ) can effectively detect Alzheimer’s disease (AD) pathophysiology in older Chinese adults and how these biomarkers correlate with astrocyte reactivity, Aβ plaque deposition, tau tangle aggregation, and neurodegeneration. Methods We recruited 470 older adults and analyzed plasma Aβ 42 /Aβ 40 , p-Tau 181 , glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. Among them, 301, 195, and 70 underwent magnetic resonance imaging, Aβ and tau positron emission tomography imaging. The plasma Aβ 42 /Aβ 40 and p-Tau 181 thresholds were defined as ≤0.0609 and ≥2.418 based on the receiver operating characteristic curve analysis using the Youden index by comparing Aβ-PET negative cognitively unimpaired individuals and Aβ-PET positive cognitively impaired patients. To evaluate the feasibility of using plasma Aβ 42 /Aβ 40 (A) and p-Tau 181 (T) to detect AD and understand how astrocyte reactivity affects this process, we compared plasma GFAP, Aβ plaque, tau tangle, plasma NfL, hippocampal volume, and temporal-metaROI cortical thickness between different plasma A/T profiles and explored their relations with each other using general linear models, including age, sex, APOE-ε4 , and diagnosis as covariates. Results Plasma A+/T + individuals showed the highest levels of astrocyte reactivity, Aβ plaque, tau tangle, and axonal degeneration, and the lowest hippocampal volume and temporal-metaROI cortical thickness. Lower plasma Aβ 42 /Aβ 40 and higher plasma p-Tau 181 were independently and synergistically correlated with higher plasma GFAP and Aβ plaque. Elevated plasma p-Tau 181 and GFAP concentrations were directly and interactively associated with more tau tangle formation. Regarding neurodegeneration, higher plasma p-Tau 181 and GFAP concentrations strongly correlated with more axonal degeneration, as measured by plasma NfL, and lower plasma Aβ 42 /Aβ 40 and higher plasma p-Tau 181 were related to greater hippocampal atrophy. Higher plasma GFAP levels were associated with thinner cortical thickness and significantly interacted with lower plasma Aβ 42 /Aβ 40 and higher plasma p-Tau 181 in predicting more temporal-metaROI cortical thinning. Voxel-wise imaging analysis confirmed these findings. Discussion This study provides a valuable reference for using plasma biomarkers to detect AD in the Chinese community population and offers novel insights into how astrocyte reactivity contributes to AD progression, highlighting the importance of targeting reactive astrogliosis to prevent AD.
Cardiac troponin T associates with left ventricular function and synchrony assessed by CMR in the general population: results from the Akershus Cardiac Examination 1950 Study
Authors: Joanna Sulkowska, Aikilu Woldegabriel Melles, Julia Brox Skranes, Trygve Berge, Arnljot Tveit, Helge Røsjø, Magnus Nakrem Lyngbakken, Torbjørn Omland, Siri Lagethon Heck
Journal:  (2024)

Abstract Background and aim Cardiac troponin T (cTnT) is a blood biomarker of myocardial injury that is associated with future adverse cardiovascular events in the general population. Left ventricular (LV) global longitudinal strain (GLS) and mechanical dispersion (MD) are metrics of systolic function and synchrony that can be obtained from cardiac imaging. Studies suggest an association between cTnT and echocardiographically assessed GLS and MD, but it is unknown whether cTnT relates to these metrics when assessed by cardiac magnetic resonance (CMR). We hypothesized that cTnT associates with GLS and with MD assessed by CMR feature tracking (CMR-FT) in the general population. Methods and results cTnT and CMR-FT measurements were performed in 186 community dwellers from the Akershus Cardiac Examination 1950 Study. The participants’ age ranged from 68 to 70 years. Median cTnT concentration was 7.0 ng/L (interquartile interval 5.0–12.6 ng/L), median absolute value of GLS was 17.3% (interquartile interval 15.7–18.8%), and median MD was 80.7 milliseconds (interquartile interval 61.8–105.0 milliseconds). In multivariable linear regression models adjusted for common clinical risk factors of cardiovascular disease, with GLS and MD as outcome and cTnT as the predictor variable of interest, log10 transformed cTnT was significantly associated with both absolute GLS [β-coefficient −1.65, confidence interval (−2.84, −0.46)] and MD [β-coefficient 28.56, confidence interval (12.14, 44.92)]. Conclusion In older adults from the general population, higher cTnT concentrations are associated with worse systolic function and synchrony assessed by CMR-FT LV GLS and MD, adding information about myocardial function to traditional risk factors.
How to Test <i>HER2</i> for Predicting Resistance to Anti-Epidermal Growth Factor Receptor Therapy in Metastatic Colorectal Cancer? Evidence From the Secondary Analysis of Biomarkers of CALGB/SWOG 80405
Authors: Andrea Sartore-Bianchi, Silvia Marsoni, Alessio Amatu, Valter Torri, Emanuela Bonoldi, Alberto Bardelli, Livio Trusolino, Salvatore Siena
Journal: Journal of Clinical Oncology (2024)
Improving Access to Patient-Focused, Decentralized Clinical Trials Requires Streamlined Regulatory Requirements: An ASCO Research Statement
Authors: Ramya Thota, Patricia A. Hurley, Therica M. Miller, Suanna S. Bruinooge, Craig Lipset, R. Donald Harvey, Lora J. Black, Amanda Dinsdale, Janette K. Merrill, Teri Pollastro, Sheila A. Prindiville, Mujahid A. Rizvi, Shimere Sherwood, Grzegorz S. Nowakowski
Journal: Journal of Clinical Oncology (2024)

Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders. ASCO held multistakeholder meetings with leaders in oncology research and concluded that research-related regulatory and administrative requirements and burdens present critical barriers to decentralizing trials. One example is sponsor and contract research organization (CRO) use of US Food and Drug Administration (FDA)'s Statement of Investigator (Form 1572), which was found to exceed FDA's stated intent and used in conservative ways disproportionate to potential risks to participants and scientific integrity. As a result, research sites experience an avalanche of downstream administrative and regulatory activities that consume considerable resources. This statement recommends four key solutions to address such barriers and recalibrate regulatory and administrative expectations for decentralizing trials: (1) FDA should engage the research community in a public-private partnership to modernize standards and enable local access to trials; (2) sponsors and CROs should develop standards and protocols that accommodate flexible approaches, enable local participation, provide clarity around roles and requirements, and promote consistency; (3) research centers, networks, and sites should update policies and procedures to implement decentralized trial elements; and (4) research community should develop a streamlined, uniform mechanism to simplify regulatory data collection and documentation and use it consistently across trials. We can and must prioritize a concerted commitment to simplify and streamline regulatory requirements and practices to broaden access to and participation in cancer clinical trials.
Can β-blockers prevent intracranial aneurysm rupture?: insights from Computational Fluid Dynamics analysis
Authors: Kornelia M Kliś, Roger M Krzyżewski, Borys M Kwinta, Krzysztof Stachura, Tadeusz J Popiela, Igor Szydłowski, Bartłomiej Łasocha, Tomasz Grodzicki, Jerzy Gąsowski
Journal: Cardiovascular Research (2024)

Abstract Aims Hypertension is a risk factor for intracranial aneurysm rupture. We analysed whether the intake of drugs from specific classes of anti-hypertensive medications affects haemodynamic parameters of intracranial aneurysm dome. Methods and results We recorded medical history including medications and the in-hospital blood pressure values. We then obtained 3D reconstruction of each patients’ aneurysm dome and the feeding artery. Using OpenFOAM software, we performed Computational Fluid Dynamics analysis of blood flow through the modelled structures. Blood was modelled as Newtonian fluid, using the incompressible transient solver. As the inlet boundary condition, we used the patient-specific Internal Carotid Artery blood velocity waves obtained with Doppler ultrasound. We calculated haemodynamic parameters of the aneurysm dome. All presented analyses are cross-sectional. We included 72 patients with a total of 91 unruptured intracranial aneurysms. The history of β-blocker intake significantly influenced haemodynamic parameters of aneurysm dome. The patients on β-blockers had significantly smaller aneurysm domes (5.09 ± 2.11 mm vs. 7.41 ± 5.89 mm; P = 0.03) and did not have aneurysms larger than 10 mm (0% vs. 17.0%; P = 0.01). In the Computational Fluid Dynamics analysis, walls of aneurysms in patients who took β-blockers were characterized by lower Wall Shear Stress Gradient (1.67 ± 1.85 Pa vs. 4.3 ± 6.06 Pa; P = 0.03), Oscillatory Shear Index (0.03 ± 0.02 vs. 0.07 ± 0.10; P = 0.04), and Surface Vortex Fraction (16.2% ± 5.2% vs. 20.0% ± 6.8%; P &amp;lt; 0.01). After controlling for covariates, we demonstrated difference of Surface Vortex Fraction (F[1, 48] = 4.36; P = 0.04) and Oscillatory Shear Index (F[1, 48] = 6.51; P = 0.01) between patients taking and not taking β-blockers, respectively. Conclusion Intake of β-blockers might contribute to more favourable haemodynamics inside aneurysmal sac. Other anti-hypertensive medication classes were not associated with differences in intracranial aneurysm parameters.
Light-activated nanoclusters with tunable ROS for wound infection treatment
Authors: Xin Wang, Jianing Ding, Xiao Chen, Sicheng Wang, Zhiheng Chen, Yuanyuan Chen, Guowang Zhang, Ji Liu, Tingwang Shi, Jian Song, Shihao Sheng, Guangchao Wang, Jianguang Xu, Jiacan Su, Wei Zhang, Xiaofeng Lian
Journal: Bioactive Materials (2024)

Infected wounds pose a significant clinical challenge due to bacterial resistance, recurrent infections, and impaired healing. Reactive oxygen species (ROS)-based strategies have shown promise in eradicating bacterial infections. However, the excess ROS in the infection site after treatments may cause irreversible damage to healthy tissues. To address this issue, we developed bovine serum albumin-iridium oxide nanoclusters (BSA-IrO
SMARCA4 controls state plasticity in small cell lung cancer through regulation of neuroendocrine transcription factors and REST splicing
Authors: Esther Redin, Harsha Sridhar, Yingqian A. Zhan, Barbara Pereira Mello, Hong Zhong, Vidushi Durani, Amin Sabet, Parvathy Manoj, Irina Linkov, Juan Qiu, Richard P. Koche, Elisa de Stanchina, Maider Astorkia, Doron Betel, Álvaro Quintanal-Villalonga, Charles M. Rudin
Journal: Journal of Hematology & Oncology (2024)

Small Cell Lung Cancer (SCLC) can be classified into transcriptional subtypes with distinct degrees of neuroendocrine (NE) differentiation. Recent evidence supports plasticity among subtypes with a bias toward adoption of low-NE states during disease progression or upon acquired chemotherapy resistance. Here, we identify a role for SMARCA4, the catalytic subunit of the SWI/SNF complex, as a regulator of subtype shift in SCLC.
Status and timing of angiotensin receptor–neprilysin inhibitor implementation in patients with heart failure and reduced ejection fraction: Data from the Swedish Heart Failure Registry
Authors: Davide Stolfo, Lina Benson, Felix Lindberg, Ulf Dahlström, Oskar Käck, Gianfranco Sinagra, Lars H. Lund, Gianluigi Savarese
Journal: European Journal of Heart Failure (2024)

We explored timing, settings and predictors of angiotensin receptor-neprilysin inhibitor (ARNI) initiation in a large, nationwide cohort of patients with heart failure (HF) with reduced ejection fraction (HFrEF).
Modelling the demographic history of human North African genomes points to a recent soft split divergence between populations
Authors: Jose M. Serradell, Jose M. Lorenzo-Salazar, Carlos Flores, Oscar Lao, David Comas
Journal: Genome biology (2024)

Abstract Background North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa. Results We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at &gt; 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa. Conclusions We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.
Using contact network dynamics to implement efficient interventions against pathogen spread in hospital settings: A modelling study
Authors: Quentin J. Leclerc, Audrey Duval, Didier Guillemot, Lulla Opatowski, Laura Temime
Journal: PLoS Medicine (2024)

Long-term care facilities (LTCFs) are hotspots for pathogen transmission. Infection control interventions are essential, but the high density and heterogeneity of interindividual contacts within LTCF may hinder their efficacy. Here, we explore how the patient-staff contact structure may inform effective intervention implementation.
Negative Pressure Ventilation Can Prevent Ventilator-associated Brain Injury
Authors: Clementina M. van Rijn, James H. M. Roberts, Malcolm G. Coulthard, Heather J. Lambert, David S. McKeown, David J. Howard, Jan van Egmond
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Negative Pressure Ventilation Can Prevent Ventilator-associated Brain Injury." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Myocardial Calcification: Case Reports and Systematic Review
Authors: Takashi Kido, Kazuki Tanimoto, Takuji Watanabe, Masaki Taira, Jun Narita, Hidekazu Ishida, Ryo Ishii, Takayoshi Ueno, Shigeru Miyagawa
Journal:  (2024)

Myocardial calcification is an unusual condition in which excess calcium is deposited in the myocardium. Herein, we report two cases of myocardial calcification from our clinical experience. Furthermore, we conduct a systematic review to examine the clinical course and associated pathologies of myocardial calcification.
REXO5 promotes genomic integrity through regulating R-loop using its exonuclease activity
Authors: Ye Jin Lee, Seo Yun Lee, Soomi Kim, Soo-Hyun Kim, Soo Hyeon Lee, Sungho Park, Jae Jin Kim, Dong-Wook Kim, Hongtae Kim
Journal: Leukemia (2024)

Chronic myeloid leukemia (CML), caused by BCR::ABL1 fusion gene, is known to regulate disease progression by altering the expression of genes. However, the molecular mechanisms underlying these changes are largely unknown. In this study, we identified RNA Exonuclease 5 (REXO5/LOC81691) as a novel gene with elevated mRNA expression levels in chronic myeloid leukemia (CML) patients. Additionally, using the REXO5 knockout (KO) K562 cell lines, we revealed a novel role for REXO5 in the DNA damage response (DDR). Compared to wild-type (WT) cells, REXO5 KO cells showed an accumulation of R-loops and increased DNA damage. We demonstrated that REXO5 translocates to sites of DNA damage through its RNA recognition motif (RRM) and selectively binds to R loops. Interestingly, we identified that REXO5 regulates R-loop levels by degrading mRNA within R-loop using its exonuclease domain. REXO5 KO showed ATR-CHK1 activation. Collectively, we demonstrated that REXO5 plays a key role in the physiological control of R-loops using its exonuclease domain. These findings may provide novel insights into how REXO5 expression changes contribute to CML pathogenesis.
Tumor evolution analysis uncovered immune-escape related mutations in relapse of diffuse large B-cell lymphoma
Authors: Xueshuai Han, Jingru Sui, Kui Nie, Yang Zhao, Xuan Lv, Jindou Xie, Leonard Tan, Rex K. H. Au-Yeung, Jiao Ma, Giorgio Inghirami, Olivier Elemento, Wayne Tam, Zhaoqi Liu
Journal: Leukemia (2024)