tbuckley/cabot-search huggingface dataset:
Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease
Authors: Gennaro Pagano, Kirsten I. Taylor, Judith Anzures Cabrera, Tanya Simuni, Kenneth Marek, Ronald B. Postuma, Nicola Pavese, Fabrizio Stocchi, Kathrin Brockmann, Hanno Svoboda, Dylan Trundell, Annabelle Monnet, Rachelle Doody, Paulo Fontoura, Geoffrey A. Kerchner, Patrik Brundin, Tania Nikolcheva, Azad Bonni
Journal: Nature Medicine (2024)

Abstract Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson’s disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab’s potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus &lt;60 years); sex (male versus female); disease duration (&gt;12 months versus &lt;12 months); age at diagnosis (≥60 years versus &lt;60 years); motor subphenotypes (akinetic–rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson’s disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.
Long-Term Follow-up of Patients With Autonomous Thyroid Nodules Treated With Radioiodine
Authors: Débora Moroto, Isabel C. O. Torquato-Vieira, Lia B. Fiorin, Cléber P. Camacho, Mário Luiz V. Castiglioni, Rui M. B. Maciel, Reinaldo P. Furlanetto, Luiza K. Matsumura, Carolina C. P. S. Janovsky, Susan C. Lindsey, João Roberto M. Martins
Journal: Clinical Nuclear Medicine (2024)

Purpose This article aims to describe the presentation of Plummer disease and its evolution after radioiodine treatment and determine factors that may influence treatment efficacy. Patients and Methods The sample included retrospective medical records of 165 adult patients with toxic nodular goiter treated with radioiodine between 1997 and 2017, followed up at a single thyroid center. Results The efficacy of treatment with a single dose of radioiodine was higher than 90%. The mean radioiodine activity was 28.9 ± 3.4 mCi. The mean time between radioiodine performance and hyperthyroidism resolution was 3.6 ± 3.0 months, ranging from 1–12 months. After the first year, 33.9% of the patients were under hypothyroidism, 59.4% under euthyroidism, and 6.7% under hyperthyroidism. Among the nonresponders, the variables that showed statistical difference were the presence of multinodular goiter and the radioiodine activity (mean, 25.5 ± 6.5 mCi; median, 30 [15–30 mCi]). The cumulative rate of hypothyroidism was 48.9% over 20 years of follow-up. Conclusions Radioiodine therapy is an effective and safe treatment. In Plummer disease, high rates of euthyroidism are expected after the radioiodine treatment. Therapeutic failure was observed mainly in patients with larger multinodular goiters treated with lower doses of radioiodine. The evolution to hypothyroidism was mostly observed in younger patients with larger and uninodular goiters.
Imaging associations enhance the understanding of ECG abnormalities in male Brazilian football players: findings from the B-Pro Foot ECG study
Authors: Filipe Ferrari, Anderson D da Silveira, Patrícia K Ziegelmann, Haroldo Aleixo, Guilherme D Dilda, Luiz G M Emed, Flávia C O Magalhães, Fernando B Cardoso, Henrique C da Silva, Felipe E F Guerra, Luciano G Soares, Fernando Bassan, Fabrício Braga, Artur H Herdy, Victor Froelicher, Ricardo Stein
Journal: British Journal of Sports Medicine (2024)

Objectives To evaluate the prevalence of abnormal ECG findings and their association with imaging results in male Brazilian football players. Methods The ‘B-Pro Foot ECG’ is a multicentre observational study conducted in 82 Brazilian professional clubs. It analysed 6125 players aged 15–35 years (2496 white, 2004 mixed-race and 1625 black individuals) who underwent cardiovascular screening from 2002 to 2023. All ECGs were reviewed by two experienced cardiologists in the athlete’s care. Those with abnormal findings underwent further investigations, including a transthoracic echocardiogram (TTE). Cardiac magnetic resonance (CMR) was subsequently performed based on TTE findings or clinical suspicion. Results In total, 180 (3%) players had abnormal ECGs and 176 (98%) showed normal TTE results. Athletes aged 26–35 years had a higher prevalence of abnormal ECGs than younger athletes (15–25 years). Black players had a higher prevalence of T-wave inversion (TWI) in the inferior leads than white players (2.6% vs 1.4%; p=0.005), as well as in V5 (2.9%) and V6 (2.1%) compared with white (1.2% and 1.0%; p&lt;0.001) and mixed-race (1.5% and 1.2%; p&lt;0.05) players, respectively. TTE parameters were similar across ethnicities. However, four out of 75 players with inferolateral TWI showed abnormal TTEs and CMR findings consistent with cardiomyopathies. CMR also showed cardiomyopathies or myocarditis in four players with inferolateral TWI and normal TTEs. In total, nine (0.1%) athletes were diagnosed with cardiac diseases and were followed for 40±30 months, with no cardiac events documented. Conclusion This study found a 3% prevalence of abnormal ECGs in male Brazilian football players. Inferolateral TWI was associated with cardiac pathologies confirmed by CMR, even in athletes with a normal TTE.
Enhancing Cerebral Amyloid Angiopathy–Related Inflammation Diagnosis With PET Using Pittsburgh Compound B
Authors: Shinobu Adaniya, Hiroshi Matsuda, Masaki Tomori, Chikako Kaneko, Noriaki Tomura
Journal: Clinical Nuclear Medicine (2024)

Abstract Cerebral amyloid angiopathy–related inflammation is a rare encephalopathy characterized by inflammation against amyloid protein accumulated in cerebral small vessels. A 50-year-old man was presented with a subacute consciousness disorder. Brain MRI revealed high intensity lesions in the white matter of the right parietal and occipital lobes on fluid-attenuated inversion recovery sequences and cerebral microbleeds in the right parietal and occipital lobes on T2*-weighted images. Pittsburgh compound B-PET demonstrated accumulation in the right temporoparietal lobe, confirming a potential diagnosis of probable cerebral amyloid angiopathy–related inflammation without brain biopsy. Steroid pulse therapy was initiated, with good results.
The Efficacy and Safety of Andexanet Alfa in Patients With Acute Gastrointestinal Bleeding While Taking Factor Xa Inhibitors: An ANNEXA-4 Subanalysis
Authors: Deborah M. Siegal, Nauzer Forbes, John Eikelboom, Jan Beyer-Westendorf, Alexander T. Cohen, Lizhen Xu, Stuart J. Connolly, Mark Crowther
Journal: Circulation (2024)
Fitusiran reduces bleeding in Factor X-deficient mice
Authors: Sebastien Verhenne, Geneviève McCluskey, Hortense Maynadié, Frédéric Adam, Caterina Casari, Laurence Panicot-Dubois, Lydie Crescence, Christophe Dubois, Cécile V. Denis, Peter J. Lenting, Olivier D. Christophe
Journal: Blood (2024)
Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies
Authors: Petra Langerbeins, Adam Giza, Sandra Robrecht, Paula Cramer, Julia von Tresckow, Othman Al-Sawaf, Anna Maria Fink, Moritz Fürstenau, Nadine Kutsch, Florian Simon, Valentin Goede, Manuela Hoechstetter, Carsten Utoft Niemann, Caspar da Cunha-Bang, Arnon Kater, Julie Dubois, Michael Gregor, Philipp Bernhard Staber, Eugen Tausch, Christof Schneider, Stephan Stilgenbauer, Barbara Eichhorst, Kirsten Fischer, Michael Hallek
Journal: Blood (2024)
Acalabrutinib, venetoclax, and obinutuzumab in relapsed/refractory CLL: final efficacy and ctDNA analysis of the CLL2-BAAG trial
Authors: Moritz Fürstenau, Adam Giza, Jonathan Weiss, Fanni Kleinert, Sandra Robrecht, Fabian Franzen, Janina Stumpf, Petra Langerbeins, Othman Al-Sawaf, Florian Simon, Anna-Maria Fink, Christof Schneider, Eugen Tausch, Johannes Schetelig, Peter Dreger, Sebastian Böttcher, Kirsten Fischer, Karl-Anton Kreuzer, Matthias Ritgen, Anke Schilhabel, Monika Brüggemann, Stephan Stilgenbauer, Barbara Eichhorst, Michael Hallek, Paula Cramer
Journal: Blood (2024)
Sudan is facing a devastating humanitarian crisis—the world must do more to protect the population’s health
Authors: Tedros Adhanom Ghebreyesus
Journal: BMJ (2024)

Sudan is facing a devastating humanitarian crisis-the world must do more to protect the population's health Tedros Adhanom Ghebreyesus directorgeneralIt's been one year since war broke out in Sudan.The country is facing a devastating humanitarian crisis, which is not attracting sufficient attention from the international community or media headlines.Half of the population, or 25 million people, are in need of humanitarian assistance. 1 Over 8.6 million people are displaced within Sudan and in neighbouring countries. 2Many of them have been forced to move multiple times.
Response by Aggarwal et al to Letter Regarding Article, “Development and Validation of the DOAC Score: A Novel Bleeding Risk Prediction Tool for Patients With Atrial Fibrillation on Direct-Acting Oral Anticoagulants”
Authors: Rahul Aggarwal, Christian T. Ruff, Saverio Virdone, Sylvie Perreault, Ajay K. Kakkar, Michael G. Palazzolo, Marc Dorais, Gloria Kayani, Robert W. Yeh
Journal: Circulation (2024)
Predicting the risks of kidney failure and death in adults with moderate to severe chronic kidney disease
Authors: Thomas Alexander Gerds, Pietro Ravani
Journal: BMJ (2024)

The risk prediction model for kidney failure and death in people with chronic kidney disease (CKD) presented in the linked study is a super learner. A super learner is an algorithm that repeatedly splits the data into training and test sets and then chooses the best performing model from a list of candidate prediction models. This article describes why and how the super learner was implemented in the linked study.
Predicting the outcomes of chronic kidney disease in older adults
Authors: Andre Pascal Kengne, Cindy George, Oluwatoyin Idaomeh Ameh
Journal: BMJ (2024)

Clinical prediction models use mathematical functions to combine information from an individual's characteristics and use the resulting output to estimate the chances that a condition of interest is present (diagnostic models) or will occur in the future (prognostic models). 1 These estimates are in turn used to start or withhold treatments, to order new tests, or to educate individuals on their condition's outlook.
Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials
Authors: Laura M. Jacobsen, David Cuthbertson, Brian N. Bundy, Mark A. Atkinson, Wayne Moore, Michael J. Haller, William E. Russell, Stephen E. Gitelman, Kevan C. Herold, Maria J. Redondo, Emily K. Sims, Diane K. Wherrett, Antoinette Moran, Alberto Pugliese, Peter A. Gottlieb, Jay M. Sosenko, Heba M. Ismail
Journal: Diabetes Care (2024)

OBJECTIVE Mixed-meal tolerance test–stimulated area under the curve (AUC) C-peptide at 12–24 months represents the primary end point for nearly all intervention trials seeking to preserve β-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy. RESEARCH DESIGN AND METHODS We examined data from six Type 1 Diabetes TrialNet immunotherapy randomized controlled trials in a post hoc analysis and included additional stimulated metabolic indices beyond C-peptide AUC. We partitioned the analysis into successful and unsuccessful trials and analyzed the data both in the aggregate as well as individually for each trial. RESULTS Among trials meeting their primary end point, we identified a treatment effect at 3 and 6 months when using C-peptide AUC (P = 0.030 and P &amp;lt; 0.001, respectively) as a dynamic measure (i.e., change from baseline). Importantly, no such difference was seen in the unsuccessful trials. The use of C-peptide AUC as a 6-month dynamic measure not only detected treatment efficacy but also suggested long-term C-peptide preservation (R2 for 12-month C-peptide AUC adjusted for age and baseline value was 0.80, P &amp;lt; 0.001), and this finding supported the concept of smaller trial sizes down to 54 participants. CONCLUSIONS Early dynamic measures can identify a treatment effect among successful immune therapies in type 1 diabetes trials with good long-term prediction and practical sample size over a 6-month period. While external validation of these findings is required, strong rationale and data exist in support of shortening early-phase clinical trials.
TCTAP A-045 Reconstructive Surgery of the Infrainguinal Arterial Segment in Patients With Chronic and Subcritical Ischemia of the Lower Extremities: A One-Year Experience of a New Vascular Center
Authors: Leonid Ladyshenskij, Anastasiia Sochnieva, Veronika Sliziuk, Paulina Labun
Journal: Journal of the American College of Cardiology (2024)
TCTAP A-039 Efficacy and Safety of Angiotensin Receptor-Neprilysin Inhibitor Versus Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker in Acute Myocardial Infarction Patients: A Meta-Analysis of Randomized Controlled Trials
Authors: Muammar Emir Ananta, Ignatius Ivan, Alya Darin Wijaya, Chabib Fachry Albab, Siska Danny
Journal: Journal of the American College of Cardiology (2024)
TCTAP C-154 Impella Assisted Percutaneous Coronary Intervention for In-Stent Restenosis of Right Coronary Artery Stent Jutting Out Into Aorta for a Patient in Cardiogenic Shock
Authors: Lakshmi Durga Kumaraguruparan, Subashini Subramanian, Nagendra Boopathy Senguttuvan, Ramesh Sankaran, Vinod Kumar Balakrishnan, S. Sadhanandham, Thoddi Ramamurthy Muralidharan, Sadagopan Thanikachalam
Journal: Journal of the American College of Cardiology (2024)
TCTAP C-195 Unveiling the Overlooked: Subclavian Steal Syndrome as an Underrecognized Neurovascular Culprit
Authors: Hanestya Oky Hermawan, Putu Dwipa Krisna Devi, Primasitha Maharany Harsoyo, Mohammad Budiarto, J. Nugroho Eko Putranto
Journal: Journal of the American College of Cardiology (2024)
TCTAP A-062 Optical Coherence Tomography-Guided or Intravascular Ultrasound-Guided PCI for True Bifurcation Lesions in the OCTIVUS Trial
Authors: Seongbong Wee, Do-Yoon Kang, Duk-Woo Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2024)
Hierarchical self-recognition and response in CSC and non-CSC micro-niches for cancer therapy
Authors: Yiliang Yang, Yiwei Peng, Yitian Du, Meng Lin, Jiajia Li, Datong Gao, Zhenzhen Yang, Wei Wang, Yanxia Zhou, Xinru Li, Taiqiang Yan, Xianrong Qi
Journal: Biomaterials (2024)
The genome and population genomics of allopolyploid Coffea arabica reveal the diversification history of modern coffee cultivars
Authors: Jarkko Salojärvi, Aditi Rambani, Zhe Yu, Romain Guyot, Susan Strickler, Maud Lepelley, Cui Wang, Sitaram Rajaraman, Pasi Rastas, Chunfang Zheng, Daniella Santos Muñoz, João Meidanis, Alexandre Rossi Paschoal, Yves Bawin, Trevor J. Krabbenhoft, Zhen Qin Wang, Steven J. Fleck, Rudy Aussel, Laurence Bellanger, Aline Charpagne, Coralie Fournier, Mohamed Kassam, Gregory Lefebvre, Sylviane Métairon, Déborah Moine, Michel Rigoreau, Jens Stolte, Perla Hamon, Emmanuel Couturon, Christine Tranchant-Dubreuil, Minakshi Mukherjee, Tianying Lan, Jan Engelhardt, Peter Stadler, Samara Mireza Correia De Lemos, Suzana Ivamoto Suzuki, Ucu Sumirat, Ching Man Wai, Nicolas Dauchot, Simon Orozco-Arias, Andrea Garavito, Catherine Kiwuka, Pascal Musoli, Anne Nalukenge, Erwan Guichoux, Havinga Reinout, Martin Smit, Lorenzo Carretero-Paulet, Oliveiro Guerreiro Filho, Masako Toma Braghini, Lilian Padilha, Gustavo Hiroshi Sera, Tom Ruttink, Robert Henry, Pierre Marraccini, Yves Van de Peer, Alan Andrade, Douglas Domingues, Giovanni Giuliano, Lukas Mueller, Luiz Filipe Pereira, Stephane Plaisance, Valerie Poncet, Stephane Rombauts, David Sankoff, Victor A. Albert, Dominique Crouzillat, Alexandre de Kochko, Patrick Descombes
Journal: Nature Genetics (2024)

Abstract Coffea arabica , an allotetraploid hybrid of Coffea eugenioides and Coffea canephora , is the source of approximately 60% of coffee products worldwide, and its cultivated accessions have undergone several population bottlenecks. We present chromosome-level assemblies of a di-haploid C. arabica accession and modern representatives of its diploid progenitors, C. eugenioides and C. canephora . The three species exhibit largely conserved genome structures between diploid parents and descendant subgenomes, with no obvious global subgenome dominance. We find evidence for a founding polyploidy event 350,000–610,000 years ago, followed by several pre-domestication bottlenecks, resulting in narrow genetic variation. A split between wild accessions and cultivar progenitors occurred ~30.5 thousand years ago, followed by a period of migration between the two populations. Analysis of modern varieties, including lines historically introgressed with C. canephora , highlights their breeding histories and loci that may contribute to pathogen resistance, laying the groundwork for future genomics-based breeding of C. arabica .
Microplastic contamination in rivers: a survey from the Nan River, Thailand
Authors: Kewalin Kongkamee, Apinya Chaimee, Pantip Hinhumpatch, Nithra Kitreerawutiwong, Romnalin Keanjoom, Sudawadee Yasaka
Journal: The Lancet Planetary Health (2024)

<h2>Abstract</h2><h3>Background</h3> Since the 1970s, microplastic contamination has been discovered in various environments. These emerging pollutants threaten water quality and freshwater ecosystems. We aimed to assess microplastic contamination in the Nan River by quantifying their presence, characterising their morphology, and identifying their polymer composition. <h3>Methods</h3> The survey was conducted along the Nan River in northern Thailand, which is divided into three distinct zones based on land use (ie, community areas, agricultural areas, and natural areas). A wide array of samples, including surface water, sediment, and specimens from five aquatic species—<i>Barbonymus altus, Laides hexanema, Kryptopterus cryptopterus, Pomacea canaliculata</i>, and <i>Pseudodon cambodjensis cambodjensis</i>—were collected. The presence of microplastics was analysed via the wet peroxide oxidation process for sample digestion, morphological characteristics were assessed through microscopic examination, and Fourier transform infrared spectrophotometry was used to identify the polymer composition of the microplastics. <h3>Findings</h3> Natural areas had the highest mean concentration of microplastics in surface water (23·67 pcs/L, SD 14·22), whereas community areas had the highest mean concentration in soil sediment (24·67 pcs/g, 15·04). No statistically significant differences in the amounts of microplastics were observed among the various land-use zones. Microplastics were predominantly found in the gastrointestinal tracts of fish specimens, with varying quantities observed among different aquatic species; <i>B altus</i> had the highest concentration (11·80 pcs/g, 8·98). The primary microplastic shapes identified were filaments (53·99%), fragments (35·58%), and cylindrical forms (10·43%). We identified ten different polymer types, with polypropylene, nylons, and polymethyl methacrylate being the most prevalent among them. <h3>Interpretation</h3> Analysing microplastic pollution in this area brings attention to the issues affecting the rivers of Thailand and emphasises ecological risks, particularly microplastic presence in aquatic species. Because of the Nan River's ecological importance, we call for increased research and collaboration to address the increasing threat of microplastic pollution. <h3>Funding</h3> Naresuan University.
Discovery and characterization of novel potent non-covalent small molecule inhibitors targeting papain-like protease from SARS-CoV-2
Authors: Miao Zheng, Bo Feng, Yumin Zhang, Xin Liu, Na Zhao, Hui Liu, Zichao Xu, Xinheng He, Zhiyan Qu, Shizhao Chen, Zhidong Jiang, Xi Cheng, Hong Liu, Yi Zang, Linxiang Zhao, Jie Zheng, Leike Zhang, Jia Li, Yu Zhou
Journal: Acta Pharmaceutica Sinica B (2024)
Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum
Authors: Joline Ingels, Laurenz De Cock, Dieter Stevens, Rupert L. Mayer, Fabien Théry, Guillem Sanchez Sanchez, David Vermijlen, Karin Weening, Saskia De Smet, Nele Lootens, Marieke Brusseel, Tasja Verstraete, Jolien Buyle, Eva Van Houtte, Pam Devreker, Kelly Heyns, Stijn De Munter, Sandra Van Lint, Glenn Goetgeluk, Sarah Bonte, Lore Billiet, Melissa Pille, Hanne Jansen, Eva Pascal, Lucas Deseins, Lies Vantomme, Maarten Verdonckt, Ria Roelandt, Thomas Eekhout, Niels Vandamme, Georges Leclercq, Tom Taghon, Tessa Kerre, Floris Vanommeslaeghe, Annemieke Dhondt, Liesbeth Ferdinande, Jo Van Dorpe, Liesbeth Desender, Frederic De Ryck, Frank Vermassen, Veerle Surmont, Francis Impens, Björn Menten, Karim Vermaelen, Bart Vandekerckhove
Journal: Cell Reports Medicine (2024)

Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial in which a dendritic cell (DC) vaccine targeting patient-individual neoantigens is evaluated in patients with resected NSCLC. Vaccine manufacturing is feasible in six of 10 enrolled patients. Toxicity is limited to grade 1-2 adverse events. Systemic T cell responses are observed in five out of six vaccinated patients, with T cell responses remaining detectable up to 19 months post vaccination. Single-cell analysis indicates that the responsive T cell population is polyclonal and exhibits the near-entire spectrum of T cell differentiation states, including a naive-like state, but excluding exhausted cell states. Three of six vaccinated patients experience disease recurrence during the follow-up period of 2 years. Collectively, these data support the feasibility, safety, and immunogenicity of this treatment in resected NSCLC.