tbuckley/cabot-search huggingface dataset:
Phylogenetic Analysis of 590 Species Reveals Distinct Evolutionary Patterns of Intron-Exon Gene Structures Across Eukaryotic Lineages
Authors: Lior Glick, Silvia Castiglione, Gil Loewenthal, Pasquale Raia, Tal Pupko, Itay Mayrose
Journal: Molecular Biology and Evolution (2024)

Introns are highly prevalent in most eukaryotic genomes. Despite the accumulating evidence for benefits conferred by the possession of introns, their specific roles and functions, as well as the processes shaping their evolution, are still only partially understood. Here we explore the evolution of the eukaryotic intron-exon gene structure by focusing on several key features such as the intron length, the number of introns, and the intron-to-exon length ratio in protein-coding genes. We utilize whole genome data from 590 species covering the main eukaryotic taxonomic groups and analyze them within a statistical phylogenetic framework. We found that the basic gene structure differs markedly among the main eukaryotic groups, with animals, and particularly chordates, displaying intron-rich genes, compared to plants and fungi. Reconstruction of gene structure evolution suggests that these differences evolved prior to the divergence of the main phyla and have remained mostly conserved within groups. We revisit the previously reported association between the genome size and the mean intron length, and report that this association differs considerably among phyla. Analyzing a large and diverse dataset of species with whole genome information while applying advanced modeling techniques allowed us to obtain a global evolutionary perspective. Our findings may indicate that introns play different molecular and evolutionary roles in different organisms.
Neuro-Oncological Superiority of Supratotal Resection in Lower-Grade Gliomas
Authors: Alberto L Gallotti, Marco Rossi, Marco Conti Nibali, Tommaso Sciortino, Lorenzo G Gay, Guglielmo Puglisi, Antonella Leonetti, Francesco Bruno, Roberta Rudà, Riccardo Soffietti, Gabriella Cerri, Lorenzo Bello
Journal: Neuro-Oncology (2024)

Supratotal-Resection (SpTR) is a promising surgical strategy in Lower-grade gliomas (LGGs). SpTR assessment, feasibility and distinctive features, as well as clinical benefit at first and second surgery and on overall-survival must be better characterized. The critical percentage of resection exceeding FLAIR margins to obtain clinical benefit and its impact on long-term functional performance are also undefined.
Practical and statistical aspects of subgroup analyses in surgical neuro-oncology: A comprehensive review from the PIONEER Consortium
Authors: Jasper K W Gerritsen, Philipp Karschnia, Jacob S Young, Martin J van den Bent, Susan M Chang, Timothy R Smith, Brian V Nahed, Jordina Rincon-Torroella, Chetan Bettegowda, Nader Sanai, Sandro M Krieg, Takashi Maruyama, Philippe Schucht, Marike L D Broekman, Joerg-Christian Tonn, Patrick Y Wen, Steven De Vleeschouwer, Arnaud J P E Vincent, Shawn Hervey-Jumper, Mitchel S Berger, Rania A Mekary, Annette M Molinaro
Journal: Neuro-Oncology (2024)

Subgroup analyses are essential to generate new hypotheses or to estimate treatment effects in clinically meaningful subgroups of patients. They play an important role in taking the next step towards personalized surgical treatment for brain tumor patients. However, subgroup analyses must be used with consideration and care because they have significant potential risks. Although some recommendations are available on the pearls and pitfalls of these analyses, a comprehensive guide is lacking, especially one focused on surgical neuro-oncology patients. This paper, therefore, reviews and summarizes for the first time comprehensively the practical and statistical considerations that are critical to this field. First, we evaluate the considerations when choosing a study design for surgical neuro-oncology studies and examine those unique to this field. Second, we give an overview of the relevant aspects to interpret subgroup analyses adequately. Third, we discuss the practical and statistical elements necessary to appropriately design and use subgroup analyses. The paper aims to provide an in-depth and complete guide to better understand risk modeling and assist the reader with practical examples of designing, using, and interpreting subgroup analyses.
Predicting control of cardiovascular disease risk factors in South Asia using machine learning
Authors: Anna Reuter, Mohammed K. Ali, Viswanathan Mohan, Lydia Chwastiak, Kavita Singh, K. M. Venkat Narayan, Dorairaj Prabhakaran, Nikhil Tandon, Nikkil Sudharsanan
Journal: npj Digital Medicine (2024)

A substantial share of patients at risk of developing cardiovascular disease (CVD) fail to achieve control of CVD risk factors, but clinicians lack a structured approach to identify these patients. We applied machine learning to longitudinal data from two completed randomized controlled trials among 1502 individuals with diabetes in urban India and Pakistan. Using commonly available clinical data, we predict each individual's risk of failing to achieve CVD risk factor control goals or meaningful improvements in risk factors at one year after baseline. When classifying those in the top quartile of predicted risk scores as at risk of failing to achieve goals or meaningful improvements, the precision for not achieving goals was 73% for HbA1c, 30% for SBP, and 24% for LDL, and for not achieving meaningful improvements 88% for HbA1c, 87% for SBP, and 85% for LDL. Such models could be integrated into routine care and enable efficient and targeted delivery of health resources in resource-constrained settings.
Early Restrictive vs Liberal Oxygen for Trauma Patients
Authors: Tobias Arleth, Josefine Baekgaard, Volkert Siersma, Andreas Creutzburg, Felicia Dinesen, Oscar Rosenkrantz, Johan Heiberg, Dan Isbye, Søren Mikkelsen, Peter M. Hansen, Stine T. Zwisler, Søren Darling, Louise B. Petersen, Maria C. R. Mørkeberg, Mikkel Andersen, Christian Fenger-Eriksen, Peder T. Bach, Mark G. Van Vledder, Esther M. M. Van Lieshout, Niki A. Ottenhof, Iscander M. Maissan, Dennis Den Hartog, Wolf E. Hautz, Dominik A. Jakob, Manuela Iten, Matthias Haenggi, Roland Albrecht, Jochen Hinkelbein, Markus Klimek, Lars S. Rasmussen, Jacob Steinmetz, Amanda Cleemann Wang, Helene Dalsten, Carl Johan Queitsch, Caroline Hjelmdal, Pernille Pape, Susanne Janum, Louise Lind Petersen, Annika Birgisdóttir Hansen, Kristin Dunlop, Liv Christiansdóttir Nielsen, Rannvá Stantcheva, Nivi Kousgaard, Heidi Marika Pokka, Klara Amalie Berthelsen Bäck, Albert Palmquist, Lasse Byskov Petersen, Lars Henrik Østergaard, Reinout Campfens, Zynab Zia, Niek Vianen, Matijs Palmans, Jasper van Bommel, Rob Verdonschot, Michael Lehmann, Marco Ambühl, Pascal Hänzi
Journal: JAMA (2024)

Early administration of supplemental oxygen for all severely injured trauma patients is recommended, but liberal oxygen treatment has been associated with increased risk of death and respiratory complications.
NRF2 activation in the heart induces glucose metabolic reprogramming and reduces cardiac dysfunction via upregulation of the pentose phosphate pathway
Authors: Anna Zoccarato, Ioannis Smyrnias, Christina M Reumiller, Anne D Hafstad, Mei Chong, Daniel A Richards, Celio X C Santos, Asjad Visnagri, Sharwari Verma, Daniel I Bromage, Min Zhang, Xiaohong Zhang, Greta Sawyer, Richard Thompson, Ajay M Shah
Journal: Cardiovascular Research (2024)

The transcription factor NRF2 is well recognized as a master regulator of antioxidant responses and cytoprotective genes. Previous studies showed that NRF2 enhances resistance of mouse hearts to chronic hemodynamic overload at least in part by reducing oxidative stress. Evidence from other tissues suggests that NRF2 may modulate glucose intermediary metabolism but whether NRF2 has such effects in the heart is unclear. Here, we investigate the role of NRF2 in regulating glucose intermediary metabolism and cardiac function during disease stress.
Justification, margin values, and analysis populations for oncologic noninferiority and equivalence trials: a meta-epidemiological study
Authors: Troy J Kleber, Alexander D Sherry, Andrew J Arifin, Gabrielle S Kupferman, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Esther J Beck, Avital M Miller, Adina H Passy, Zachary R Mccaw, Pavlos Msaouel, Ethan B Ludmir
Journal: JNCI Journal of the National Cancer Institute (2024)

Noninferiority (NI) and equivalence trials evaluate whether an experimental therapy's effect on the primary endpoint (PEP) is contained within an acceptable margin compared to standard-of-care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used.
A read-through circular RNA RCRIN inhibits metabolic dysfunction-associated steatotic liver disease
Authors: Yanying Wang, Jianyi Wang, Ziheng Zhou, None Yang Gu, Xiaoxiao Zhu, Zhibin Yi, Changchang Cao, Lei He, Ying Du, Hui Guo, Yong Tian, Zusen Fan
Journal: Journal of Hepatology (2024)

The molecular mechanism underlying metabolic dysfunction-associated steatotic liver disease (MASLD) is elusive and whether non-coding RNAs can serve as biomarkers and therapeutic targets of MASLD is less defined.
Designing a Time-Dependent Therapeutic Strategy using CDK4/6 Inhibitors in an Intracranial ATRT Model
Authors: Brice Martin, Sergio W Guadix, Rekha Sathian, Madeline Laramee, Abhinav Pandey, Ishani Ray, Amy Wang, Ramana Davuluri, Craig J Thomas, Nadia Dahmane, Mark Souweidane
Journal: Neuro-Oncology (2024)

Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6), crucial for cell cycle regulation, have shown promise in early-stage studies for treating central nervous system (CNS) tumors. However, challenges such as limited CNS penetration, optimal treatment duration, and systemic side effects have impeded their clinical translation for pediatric brain tumors (PBTs).
Biologics in Congenital Ichthyosis - an Incomplete Fix
Authors: Syed F H Shah, Edel A O’Toole
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Biologics in Congenital Ichthyosis - an Incomplete Fix Get access Syed F H Shah, Syed F H Shah Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK Corresponding author: Syed FH Shah Email:[email protected] https://orcid.org/0000-0003-0624-1246 Search for other works by this author on: Oxford Academic Google Scholar Edel A O'Toole Edel A O'Toole Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae475, https://doi.org/10.1093/bjd/ljae475 Published: 06 December 2024 Article history Received: 02 December 2024 Accepted: 05 December 2024 Published: 06 December 2024
The Role of Artificial Intelligence in Standardising Global Longitudinal Strain Measurements in Echocardiography
Authors: Krunoslav M Sveric, Roxana Botan, Anna Winkler, Zouhir Dindane, Ghatafan Alothman, Baris Cansiz, Jens Fassl, Michael Kaliske, Axel Linke
Journal:  (2024)

To evaluate the accuracy and feasibility of artificial intelligence (AI) in left ventricular global longitudinal strain (GLS) analysis as compared to conventional (Manual) and semi-automated (SemiAuto) method in echocardiography (Echo).
Targeting type 2 inflammation in bullous pemphigoid (BP): dupilumab as game changer opens new avenues
Authors: Luca Borradori, Michael Hertl
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Targeting type 2 inflammation in bullous pemphigoid (BP): dupilumab as game changer opens new avenues Get access Luca Borradori, Luca Borradori Department of Dermatology, University Hospital of Bern, University of Bern, Switzerland Correspondence: Luca Borradori1Email:[email protected] Search for other works by this author on: Oxford Academic Google Scholar Michael Hertl Michael Hertl Department of Dermatology and Allergology, Philipps University, Marburg, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae465, https://doi.org/10.1093/bjd/ljae465 Published: 06 December 2024 Article history Received: 18 November 2024 Accepted: 05 December 2024 Published: 06 December 2024
Geospatial analyses demonstrate variation of cutaneous T-cell lymphomas across Australia, providing insights into possible causes
Authors: Belinda A Campbell, Peter D Baade, Paramita Dasgupta, Jessica K Cameron, Sandro V Porceddu, H Miles Prince, Karin Thursky
Journal: British Journal of Dermatology (2024)

Cutaneous T-cell lymphomas (CTCL) are rare with distinct diagnostic challenges. Equitable access to cancer care is a recognised priority, internationally. To date, the geospatial distribution of CTCL has not been definitively studied. Understanding the incidence and geographical distribution of patients with CTCL are critical first steps towards the ultimate goal of equity of care. Geospatial analyses also allow the opportunity to explore environmental causative factors: for CTCL, the contribution of ultraviolet (UV) radiation on causation remains unclear.
Growth Hormone Action as a Target in Cancer: Significance, Mechanisms and Possible Therapies
Authors: Reetobrata Basu, Cesar L Boguszewski, John J Kopchick
Journal: Endocrine Reviews (2024)

Growth hormone (GH) is a pituitary derived endocrine hormone required for normal post-natal growth and development. Hypo or hypersecretion of endocrine GH results in two pathologic conditions, namely GH deficiency (GHD) and acromegaly. Additionally, GH is also produced in non-pituitary and tumoral tissues where it acts rather as a cellular growth factor with an autocrine/paracrine mode of action. An increasingly persuasive and large body of evidence over the last 70 years concur that GH action is implicit in escalating several cancer-associated events, locally and systemically. This pleiotropy of GH's effects is puzzling, but the association with cancer-risk automatically raises a concern for patients with acromegaly and for individuals treated with GH. By careful assessment of the available knowledge on the fundamental concepts of cancer, suggestions from epidemiological and clinical studies, and the evidence from specific reports, in this review we aimed to help clarify the distinction of endocrine vs. autocrine/paracrine GH in promoting cancer and reconcile the discrepancies between experimental and clinical data. Along this discourse, we critically weigh the targetability of GH action in cancer - firstly by detailing the molecular mechanisms which posit GH as a critical node in tumor circuitry, and secondly, by enumerating the currently available therapeutic options targeting GH action. On the basis of our discussion, we infer that a targeted intervention on GH action in the appropriate patient population can benefit a sizeable subset of current cancer prognoses.
The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catshark <i>Scyliorhinus canicula</i> reveal the molecular bases of sensory organ evolution in jawed vertebrates
Authors: H Mayeur, J Leyhr, J Mulley, N Leurs, L Michel, K Sharma, R Lagadec, J -M Aury, O G Osborne, P Mulhair, J Poulain, S Mangenot, D Mead, M Smith, C Corton, K Olive, J Skelton, E Betteridge, J Dolucan, O Dudchenko, A D Omer, D Weisz, E L Aiden, S McCarthy, Y Sims, J Torrance, A Tracey, K Howe, T Baril, A Hayward, C Martinand-Mari, S Sanchez, T Haitina, K Martin, S I Korsching, S Mazan, M Debiais-Thibaud
Journal: Molecular Biology and Evolution (2024)

Abstract Cartilaginous fishes (chondrichthyans: chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.
Stat Bite: Observed and predicted all-cancer incidence and mortality rates and numbers in four Nordic countries: 1943-2040
Journal: JNCI Journal of the National Cancer Institute (2024)

Observed and predicted all-cancer incidence and mortality rates and numbers in four Nordic countries: 1943-2040The left figure depicts the observed age-adjusted (world) incidence and mortality rates for all cancers but non-melanoma skin cancer in Denmark (1943-2022), Finland (1953-2022), Norway (1953-2023) and Sweden (1953Sweden ( -2022) ) together with the predicted rates up until 2045 based on the NORDPRED age-period-cohort model.The right figure depicts the corresponding new cancer cases and cancer deaths combined for the four countries; by 2045, the number of cancer cases and deaths per annum will reach over 200,000 and 70,000 respectively.
Skin immune-mesenchymal interplay within tertiarylymphoid structures promotes autoimmunepathogenesis in hidradenitis suppurativa
Authors: Wei-Wen Yu, Joy N.P. Barrett, Jie Tong, Meng-Ju Lin, Meaghan Marohn, Joseph C. Devlin, Alberto Herrera, Juliana Remark, Jamie Levine, Pei-Kang Liu, Victoria Fang, Abigail M. Zellmer, Derek A. Oldridge, E. John Wherry, Jia-Ren Lin, Jia-Yun Chen, Peter Sorger, Sandro Santagata, James G. Krueger, Kelly V. Ruggles, Fei Wang, Chang Su, Sergei B. Koralov, Jun Wang, Ernest S. Chiu, Catherine P. Lu
Journal: Immunity (2024)
Association between cardiometabolic diseases and the risk and progression of motor neuron diseases in Sweden: a population-based case–control study
Authors: Charilaos Chourpiliadis, Anikó Lovik, Christina Seitz, Yihan Hu, Jing Wu, Petter Ljungman, Rayomand Press, Kristin Samuelsson, Caroline Ingre, Fang Fang
Journal: The Lancet Regional Health - Europe (2024)
Predicting success with reduced dosing frequency of tralokinumab in patients with moderate-to-severe atopic dermatitis
Authors: Stephan Weidinger, Anthony Bewley, H Chih-ho Hong, Juan Francisco Silvestre, Ketty Peris, Andreas Wollenberg, Ulla Ivens, Anders Soehoel, Louise Abildgaard Steffensen, Ann-Marie Tindberg, Eric L Simpson
Journal: British Journal of Dermatology (2024)

Abstract Background Approved tralokinumab maintenance dosing regimens for treatment of moderate-to-severe atopic dermatitis (AD) include 300 mg every two weeks (Q2W) and every four weeks (Q4W), that clinicians may consider for patients who achieved clear or almost clear skin at Week 16 with initial Q2W dosing. Objectives To identify predictive factors associated with maintained response after switching to tralokinumab Q4W, evaluate recapture of treatment response after relapse on Q4W, and assess treatment-emergent immunogenicity with tralokinumab Q4W. Methods These post hoc analyses utilized machine learning to identify predictive factors for maintained treatment response at Week 52 using data from the Week 16 responder population (ie, patients who met Investigator’s Global Assessment of clear/almost clear skin [IGA 0/1] and/or ≥75% improvement in Eczema Area and Severity Index (EASI-75) at Week 16 with tralokinumab Q2W monotherapy) of the phase 3 ECZTRA 1 and 2 trials. Top-ranked factors were then assessed individually and together to identify factors associated with a similar maintained efficacy at Week 52 between patients re-randomized to tralokinumab Q2W or Q4W monotherapy at Week 16. Additionally, the probability of recapturing IGA 0/1 and/or EASI-75 response after relapse was assessed in tralokinumab Q4W patients transferred to the open-label arm. Results The two top-ranked predictive factors for maintained response at Week 52 were IGA score at Week 16 (76.1%) and worst daily pruritus numeric rating scale (NRS) &amp;lt;3 at Week 16 (56.5%). Among patients with a stable achievement of both IGA 0/1 and worst daily pruritus NRS &amp;lt;3 from Weeks 12-16 with tralokinumab Q2W, similarly high maintained IGA 0/1 response at Week 52 were seen regardless of dosing regimen beyond Week 16 (Q2W: 72.0%; Q4W: 72.2%). Of patients who relapsed on Q4W, 94.6% recaptured treatment response after returning to Q2W dosing. The immunogenicity potential of tralokinumab was low and patients with positive antidrug antibodies did not show loss of efficacy or higher incidences of adverse events. Conclusions These data suggest that Q4W is an effective dosing regimen for most patients who achieved stable disease control, as shown by clear/almost skin and no-to-mild itch over 4 consecutive weeks with tralokinumab Q2W.
Race and Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative, Node-Positive Breast Cancer in the Randomized RxPONDER Trial
Authors: Yara Abdou, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori J Goldstein, Stephen K L Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F Schott, Steven Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Joseph M Unger, Debasish Tripathy, Gabriel N Hortobagyi, Lajos Pusztai, Kevin Kalinsky
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The phase III RxPONDER trial has affected treatment for node-positive (1-3), hormone receptor-positive, HER2-negative breast cancer with a 21-gene recurrence score (RS) less than 26. We investigated how these findings apply to different racial and ethnic groups within the trial. Methods The trial randomly assigned women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS), with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathological characteristics, RS, and treatment. Results A total of 4048 women with self-reported race/ethnicity were included: Hispanic (15.1%), non-Hispanic Black (NHB) (6.1%), Native American/Pacific Islander (0.8%), Asian (8.0%), and non-Hispanic White (NHW) (70%). No differences in RS distribution, tumor size, or number of positive nodes were observed by race/ethnicity. Relative to NHWs, IDFS was worse for NHB participants (5-year IDFS 91.6% vs 87.1%, HR = 1.37; 95% CI = 1.03 to 1.81) and better for Asians (91.6% vs 93.9%, HR = 0.64; 95% CI = 0.46 to 0.91). Relative to NHW, DRFS was worse for NHB participants (5-year DRFS 95.8% vs 91.0%, HR = 1.65; 95% CI = 1.17 to 2.32) and better for Asians (95.8% vs 96.7%, HR = 0.59; 95% CI = 0.37 to 0.95). Adjusting for clinical characteristics, particularly body mass index, diminished the effect of race on outcomes. Chemotherapy treatment efficacy did not differ by race/ethnicity. Conclusions NHB women had worse clinical outcomes compared with NHWs in the RxPONDER trial despite similar RS and comparable treatment. Our study emphasizes the persistent racial disparities in breast cancer outcomes while highlighting complex interactions among contributing factors. Trial Registration ClinicalTrials.gov: NCT01272037.