tbuckley/cabot-search huggingface dataset:
Unveiling the PDK4-centered rituximab-resistant mechanism in DLBCL: the potential of the “Smart” exosome nanoparticle therapy
Authors: Xin Wu, Chunmei Ban, Woding Deng, Xuewei Bao, Ning Tang, Yupeng Wu, Zhixuan Deng, Jianbin Xiong, Qiangqiang Zhao
Journal: Molecular Cancer (2024)

Diffuse large B-cell lymphoma (DLBCL) represents a prevalent malignant tumor, with approximately 40% of patients encountering treatment challenges or relapse attributed to rituximab resistance, primarily due to diminished or absent CD20 expression. Our prior research identified PDK4 as a key driver of rituximab resistance through its negative regulation of CD20 expression. Further investigation into PDK4's resistance mechanism and the development of advanced exosome nanoparticle complexes may unveil novel resistance targets and pave the way for innovative, effective treatment modalities for DLBCL.
A survey of skin tone assessment in prospective research
Authors: Vanessa R. Weir, Katelyn Dempsey, Judy Wawira Gichoya, Veronica Rotemberg, An-Kwok Ian Wong
Journal: npj Digital Medicine (2024)

Increasing evidence supports reduced accuracy of noninvasive assessment tools, such as pulse oximetry, temperature probes, and AI skin diagnosis benchmarks, in patients with darker skin tones. The FDA is exploring potential strategies for device regulation to improve performance across diverse skin tones by including skin tone criteria. However, there is no consensus about how prospective studies should perform skin tone assessment in order to take this bias into account. There are several tools available to conduct skin tone assessments including administered visual scales (e.g., Fitzpatrick Skin Type, Pantone, Monk Skin Tone) and color measurement tools (e.g., reflectance colorimeters, reflectance spectrophotometers, cameras), although none are consistently used or validated across multiple medical domains. Accurate and consistent skin tone measurement depends on many factors including standardized environments, lighting, body parts assessed, patient conditions, and choice of skin tone assessment tool(s). As race and ethnicity are inadequate proxies for skin tone, these considerations can be helpful in standardizing the effect of skin tone on studies such as AI dermatology diagnoses, pulse oximetry, and temporal thermometers. Skin tone bias in medical devices is likely due to systemic factors that lead to inadequate validation across diverse skin tones. There is an opportunity for researchers to use skin tone assessment methods with standardized considerations in prospective studies of noninvasive tools that may be affected by skin tone. We propose considerations that researchers must take in order to improve device robustness to skin tone bias.
Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group
Authors: Yidian Gao, Marlene Staginnus, Yidian Gao, Marlene Staginnus, Sophie Townend, Celso Arango, Sahil Bajaj, Tobias Banaschewski, Edward D. Barker, Vivek Benegal, Kathryn Berluti, Anka Bernhard, Robert J.R. Blair, Charlotte P.S. Boateng, Arun L.W. Bokde, Daniel Brandeis, Jan K. Buitelaar, S. Alexandra Burt, Elise M. Cardinale, Josefina Castro-Fornieles, Hui Chen, Xianliang Chen, Sally C. Chester, Olivier F. Colins, Harriet Cornwell, Michael Craig, Ana I. Cubillo, Sylvane Desrivieres, Dana E. Díaz, Andrea Dietrich, Daifeng Dong, Anouk H. Dykstra, Barbara Franke, Christine M. Freitag, Jeffrey C. Glennon, Karen Gonzalez-Madruga, Cindy C. Hagan, Pieter J. Hoekstra, Bharath Holla, Luke W. Hyde, Karim Ibrahim, Nimrah Jabeen, Rebecca L. Jackson, Yali Jiang, Gregor Kohls, Kerstin Konrad, Alexandra Kypta-Vivanco, Kim Lamers, Ren Ma, Abigail A. Marsh, Anne Martinelli, Jean-Luc Martinot, Kalina J. Michalska, Qingsen Ming, Silvia Minosse, Colter Mitchell, Christopher S. Monk, Declan Murphy, Leah E. Mycue, Jilly Naaijen, Maaike Oosterling, Luca Passamonti, Ruth Pauli, Maria Jose Penzol Alonso, Harriet Phillips, Montana L. Ploe, Nora M. Raschle, Ruth Roberts, Jack C. Rogers, Mireia Rosa-Justicia, Ilyas Sagar-Ouriaghli, Ulrike M.E. Schulze, Gunter Schumann, Arjun Sethi, Areti Smaragdi, Edmund J.S. Sonuga-Barke, Christina Stadler, Michael C. Stevens, Denis G. Sukhodolsky, Kate Sully, Xiaoqiang Sun, Nicola Toschi, Christopher D. Townsend, Nic J.A. van der Wee, Robert Vermeiren, Essi Viding, Xiaoping Wang, Heidi B. Westerman, Qiong Wu, Shuqiao Yao, Jibiao Zhang, Jiansong Zhou, Jiawei Zhou, Neda Jahanshad, Sophia I. Thomopoulos, Christopher R.K. Ching, Melody J.Y. Kang, Paul M. Thompson, Eduard T. Klapwijk, Daniel S. Pine, Arielle Baskin-Sommers, Charlotte A.M. Cecil, Moji Aghajani, Esther Walton, Graeme Fairchild, Stephane A. De Brito
Journal: The Lancet Psychiatry (2024)
Assessing the impact of health-care access on the severity of low back pain by country: a case study within the GBD framework
Authors: YiFan Wu, Sarah Wulf Hanson, Garland Culbreth, Caroline Purcell, Peter Brooks, Jacek Kopec, Lyn March, Anthony D Woolf, Maja Pasovic, Erin Hamilton, Damian Santomauro, Theo Vos
Journal: The Lancet Rheumatology (2024)

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is key for policy making. Low back pain is the leading cause of disability in terms of years lived with disability (YLDs). Due to sparse data, a current limitation of GDB is that a uniform severity distribution is presumed based on 12-Item Short Form Health Survey scores derived from US Medical Expenditure Panel Surveys (MEPS). We present a novel approach to estimate the effect of exposure to health interventions on the severity of low back pain by country and over time.
Immunogenicity and safety of an 18-month booster dose of the VLA15 Lyme borreliosis vaccine candidate after primary immunisation in healthy adults in the USA: results of the booster phase of a randomised, controlled, phase 2 trial
Authors: Santhosh Kumar Ghadge, Martina Schneider, Katrin Dubischar, Laura Wagner, Vera Kadlecek, Michaela Obersriebnig, Romana Hochreiter, Anton Klingler, Julian Larcher-Senn, Ulla Derhaschnig, Wolfgang Bender, Susanne Eder-Lingelbach, Nicole Bézay
Journal: The Lancet Infectious Diseases (2024)
Celiac plexus radiosurgery for pain management in advanced cancer: a multicentre, single-arm, phase 2 trial
Authors: Yaacov R Lawrence, Marcin Miszczyk, Laura A Dawson, Dayssy Alexandra Diaz Pardo, Artur Aguiar, Dror Limon, Raphael M Pfeffer, Michael Buckstein, Aisling S Barry, Tikva Meron, Adam P Dicker, Jerzy Wydmański, Camilla Zimmermann, Ofer Margalit, David Hausner, Ofir Morag, Talia Golan, Galia Jacobson, Sergey Dubinski, Teo Stanescu, Ronen Fluss, Laurence S Freedman, Maoz Ben-Ayun, Zvi Symon
Journal: The Lancet Oncology (2024)
Validation of independent prognostic significance of blast count in a large cohort of MDS patients
Authors: Raniah Al Amri, Vandana Baloda, Sara A Monaghan, Flavia G Rosado, Erika M Moore, Bryan Rea, Miroslav Djokic, Nidhi Aggarwal, Svetlana A Yatsenko, Nathanael G Bailey
Journal: Leukemia (2024)
Injectable citrate-based polyurethane-urea as a tug-of-war-inspired bioactive self-expansive and planar-fixing screw augmented bone-tendon healing
Authors: Meihan Tao, Zhou Fang, Yuting Zhu, Yan Ju, Zhiguo Hou, Meimei Fu, Zhihui Lu, Daozhang Cai, Jian Yang, Jinshan Guo
Journal: Bioactive Materials (2024)
Attributable mortality of candidemia – Results from the ECMM Candida III multinational European Observational Cohort Study
Authors: Jon Salmanton-García, Oliver A. Cornely, Jannik Stemler, Aleksandra Barać, Jörg Steinmann, Alena Siváková, Emin Halis Akalin, Sevtap Arikan-Akdagli, Laura Loughlin, Cristina Toscano, Manjusha Narayanan, Benedict Rogers, Birgit Willinger, Deniz Akyol, Emmanuel Roilides, Katrien Lagrou, Malgorzata Mikulska, Blandine Denis, Diane Ponscarme, Urlike Scharmann, Alpay Azap, Deborah Lockhart, Tihana Bicanic, Florian Kron, Nurettin Erben, Riina Rautemaa-Richardson, Anna L. Goodman, Carolina Garcia-Vidal, Cornelia Lass-Flörl, Jean-Pierre Gangneux, Lucia Taramasso, Maite Ruiz, Yael Schick, Eric Van Wijngaerden, Christopher Milacek, Daniele Roberto Giacobbe, Clare Logan, Emily Rooney, Andrea Gori, Murat Akova, Matteo Bassetti, Martin Hoenigl, Philipp Koehler
Journal: Journal of Infection (2024)
Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting
Authors: Karin E Sandoval, Ken A Witt
Journal: Pharmacological Reviews (2024)

Over 4 decades of research support the link between Alzheimer disease (AD) and somatostatin [somatotropin-releasing inhibitory factor (SRIF)]. SRIF and SRIF-expressing neurons play an essential role in brain function, modulating hippocampal activity and memory formation. Loss of SRIF and SRIF-expressing neurons in the brain rests at the center of a series of interdependent pathological events driven by amyloid-β peptide (Aβ), culminating in cognitive decline and dementia. The connection between the SRIF and AD further extends to the neuropsychiatric symptoms, seizure activity, and inflammation, whereas preclinical AD investigations show SRIF or SRIF receptor agonist administration capable of enhancing cognition. SRIF receptor subtype-4 activation in particular presents unique attributes, with the potential to mitigate learning and memory decline, reduce comorbid symptoms, and enhance enzymatic degradation of Aβ in the brain. Here, we review the links between SRIF and AD along with the therapeutic implications. SIGNIFICANCE STATEMENT: Somatostatin and somatostatin-expressing neurons in the brain are extensively involved in cognition. Loss of somatostatin and somatostatin-expressing neurons in Alzheimer disease rests at the center of a series of interdependent pathological events contributing to cognitive decline and dementia. Targeting somatostatin-mediated processes has significant therapeutic potential for the treatment of Alzheimer disease.
Interim Phase II Results Using Panitumumab-IRDye800CW During Transoral Robotic Surgery in Patients with Oropharyngeal Cancer
Authors: Logan D. Stone, Benjamin B. Kasten, Shilpa Rao, Manuel L. Gonzalez, Todd M. Stevens, Diana Lin, William Carroll, Benjamin Greene, Lindsay S. Moore, Andrew Fuson, Sherin James, Yolanda E. Hartman, Susan McCammon, Bharat Panuganti, Lisle M. Nabell, Yufeng Li, Mei Li, Luke Bailey, Eben L. Rosenthal, Harishanker Jeyarajan, Carissa M. Thomas, Jason M. Warram
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence-guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but exhibit the greatest potential impact for improving patient care when the surgeon receives limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in patients with OPSCC. Patients and Methods: Twelve consecutive patients with OPSCC were enrolled as part of a nonrandomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. Results: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. Conclusions: The results from this patient with OPSCC cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.
A single-cell atlas deconstructs heterogeneity across multiple models in murine traumatic brain injury and identifies novel cell-specific targets
Authors: Ruchira M. Jha, Dhivyaa Rajasundaram, Chaim Sneiderman, Brent T. Schlegel, Casey O’Brien, Zujian Xiong, Keri Janesko-Feldman, Ria Trivedi, Vincent Vagni, Benjamin E. Zusman, Joshua S. Catapano, Adam Eberle, Shashvat M. Desai, Ashutosh P. Jadhav, Sandra Mihaljevic, Margaux Miller, Sudhanshu Raikwar, Anupama Rani, Jarrod Rulney, Shima Shahjouie, Itay Raphael, Aditya Kumar, Chia-Ling Phuah, Ethan A. Winkler, Dennis W. Simon, Patrick M. Kochanek, Gary Kohanbash
Journal: Neuron (2024)

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.
The Evolution of Ultraconserved Elements in Vertebrates
Authors: Mitchell Cummins, Cadel Watson, Richard J Edwards, John S Mattick
Journal: Molecular Biology and Evolution (2024)

Ultraconserved elements (UCEs) were discovered two decades ago, arbitrarily defined as sequences that are identical over a length ≥200 bp in the human, mouse and rat genomes. The definition was subsequently extended to sequences ≥100 bp identical in at least three of five mammalian genomes (including dog and cow), and shown to have undergone rapid expansion from ancestors in fish and strong negative selection in birds and mammals. Since then, many more genomes have become available, allowing better definition and more thorough examination of UCE distribution and evolutionary history. We developed a fast and flexible analytical pipeline for identifying UCEs in multiple genomes, dedUCE, which allows manipulation of minimum length, sequence identity, and number of species with a detectable UCE according to specified parameters. We suggest an updated definition of UCEs as sequences ≥100 bp and ≥97% sequence identity in ≥50% of placental mammal orders (12813 UCEs). By mapping UCEs to ∼200 species we find that placental UCEs appeared early in vertebrate evolution, well before land colonisation, suggesting the evolutionary pressures driving UCE selection were present in aquatic environments in the Cambrian-Devonian periods. Most (>90%) UCEs likely appeared after the divergence of gnathostomes from jawless predecessors, were largely established in sequence identity by early Sarcopterygii evolution - before the divergence of lobe-finned fishes from tetrapods - and became near fixed in the amniotes. UCEs are mainly located in the introns of protein-coding and non-coding genes involved in neurological and skeletomuscular development, enriched in regulatory elements, and dynamically expressed throughout embryonic development.
Gut microbiota promotes macrophage M1 polarization in hepatic sinusoidal obstruction syndrome via regulating intestinal barrier function mediated by butyrate
Authors: Si Zhao, Han Zhang, Hanlong Zhu, Tianming Zhao, Jingjing Tu, Xiaochun Yin, Suzhen Yang, Wei Zhang, Feng Zhang, Ming Zhang, Bing Xu, Yuzheng Zhuge, Jiangqiang Xiao
Journal: Gut Microbes (2024)

Background The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options.
Comparing cervical cerclage, pessary and vaginal progesterone for prevention of preterm birth in women with a short cervix (SuPPoRT): A multicentre randomised controlled trial
Authors: Natasha L. Hezelgrave, Natalie Suff, Paul Seed, Vicky Robinson, Jenny Carter, Helena Watson, Alexandra Ridout, Anna L. David, Susana Pereira, Fatemeh Hoveyda, Joanna Girling, Latha Vinayakarao, Rachel M. Tribe, Andrew H. Shennan
Journal: PLoS Medicine (2024)

Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT "Stitch, Pessary, or Progesterone Randomised Trial" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy.
Short-Term Exposure to Wildfire-Specific PM2.5 and Hospitalization for Diabetes Morbidity: A Study in Multiple Countries and Territories
Authors: Yiwen Zhang, Rongbin Xu, Wenzhong Huang, Lidia Morawska, Fay H. Johnston, Michael Abramson, Luke Knibbs, Patricia Matus, Tingting Ye, Wenhua Yu, Simon Hales, Geoffrey Morgan, Zhengyu Yang, Yanming Liu, Ke Ju, Pei Yu, Eric Lavigne, Yao Wu, Bo Wen, Yuxi Zhang, Jane Heyworth, Guy Marks, Paulo H.N. Saldiva, Micheline S.Z.S. Coelho, Yue Leon Guo, Jiangning Song, Yuming Guo, Shanshan Li
Journal: Diabetes Care (2024)

OBJECTIVE To evaluate associations of wildfire fine particulate matter ≤2.5 mm in diameter (PM2.5) with diabetes across multiple countries and territories. RESEARCH DESIGN AND METHODS We collected data on 3,612,135 diabetes hospitalizations from 1,008 locations in Australia, Brazil, Canada, Chile, New Zealand, Thailand, and Taiwan during 2000–2019. Daily wildfire-specific PM2.5 levels were estimated through chemical transport models and machine-learning calibration. Quasi-Poisson regression with distributed lag nonlinear models and random-effects meta-analysis were applied to estimate associations between wildfire-specific PM2.5 and diabetes hospitalization. Subgroup analyses were by age, sex, location income level, and country or territory. Diabetes hospitalizations attributable to wildfire-specific PM2.5 and nonwildfire PM2.5 were compared. RESULTS Each 10 µg/m3 increase in wildfire-specific PM2.5 levels over the current day and previous 3 days was associated with relative risks (95% CI) of 1.017 (1.011–1.022), 1.023 (1.011–1.035), 1.023 (1.015–1.032), 0.962 (0.823–1.032), 1.033 (1.001–1.066), and 1.013 (1.004–1.022) for all-cause, type 1, type 2, malnutrition-related, other specified, and unspecified diabetes hospitalization, respectively. Stronger associations were observed for all-cause, type 1, and type 2 diabetes in Thailand, Australia, and Brazil; unspecified diabetes in New Zealand; and type 2 diabetes in high-income locations. An estimate of 0.67% (0.16–1.18%) and 1.02% (0.20–1.81%) for all-cause and type 2 diabetes hospitalizations were attributable to wildfire-specific PM2.5. Compared with nonwildfire PM2.5, wildfire-specific PM2.5 posed greater risks of all-cause, type 1, and type 2 diabetes and were responsible for 38.7% of PM2.5-related diabetes hospitalizations. CONCLUSIONS We show the relatively underappreciated links between diabetes and wildfire air pollution, which can lead to a nonnegligible proportion of PM2.5-related diabetes hospitalizations. Precision prevention and mitigation should be developed for those in advantaged communities and in Thailand, Australia, and Brazil.
Renovascular Disease and Mitochondrial Dysfunction in Human Mesenchymal Stem Cells
Authors: Alfonso Eirin, Sarosh Siddiqi, Autumn G. Hughes, Yamei Jiang, Xiang-Yang Zhu, Sara Kazeminia, Bo Lu, Li Xing, Brandon Lu, Hui Tang, Ailing Xue, Amir Lerman, Stephen C. Textor, Lilach O. Lerman
Journal: Journal of the American Society of Nephrology (2024)

Key Points Renovascular disease impairs the capacity of human adipose tissue–derived mesenchymal stem/stromal cells to repair ischemic murine kidneys. miR-378h modulated the capacity of renovascular disease adipose tissue–derived mesenchymal stem/stromal cells to repair ischemic kidneys in vivo . Background Renovascular disease leads to renal ischemia, hypertension, and eventual kidney failure. Autologous transplantation of adipose tissue–derived mesenchymal stem/stromal cells (MSCs) improves perfusion and oxygenation in stenotic human kidneys, but associated atherosclerosis and hypertension might blunt their effectiveness. We hypothesized that renovascular disease alters the human MSC transcriptome and impairs their reparative potency. Methods MSCs were harvested from subcutaneous abdominal fat of patients with renovascular disease and healthy volunteers ( n =3 each), characterized and subsequently injected (5×10 5 /200 μ l) into mice 2 weeks after renal artery stenosis or sham surgery ( n =6/group). Two weeks later, mice underwent imaging and tissue studies. MSCs from healthy volunteers and in those with renovascular disease were also characterized by mRNA/microRNA (miRNA) sequencing. Based on these, MSC proliferation and mitochondrial damage were assessed in vitro before and after miRNA modulation and in vivo in additional renal artery stenosis mice administered with MSCs from renovascular disease pretreated with miR-378h mimic ( n =5) or inhibitor ( n =4). Results MSCs engrafted in stenotic mouse kidneys. Healthy volunteer MSCs (but not renovascular disease MSCs) decreased BP, improved serum creatinine levels and stenotic-kidney cortical perfusion and oxygenation, and attenuated peritubular capillary loss, tubular injury, and fibrosis. Genes upregulated in renovascular disease MSCs versus healthy volunteer MSCs were mostly implicated in transcription and cell proliferation, whereas those downregulated encoded mainly mitochondrial proteins. Upregulated miRNAs, including miR-378h, primarily target nuclear-encoded mitochondrial genes, whereas downregulated miRNAs mainly target genes implicated in transcription and cell proliferation. MSC proliferation was similar, but their mitochondrial structure and reparative function both in vivo and in vitro improved after miR-378h inhibition. Conclusions Renovascular disease impaired the reparative capacity of human MSCs, possibly by dysregulating miR-378h that targets mitochondrial genes. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_08_21_ASN0000000000000440.mp3
A Snapshot of Lead in Consumer Products Across Four US Jurisdictions
Authors: Kate Porterfield, Paromita Hore, Stephen G. Whittaker, Katie M. Fellows, Anshu Mohllajee, Shakoora Azimi-Gaylon, Berna Watson, Isabel Grant, Richard Fuller
Journal: Environmental Health Perspectives (2024)

Following the removal of lead from gasoline, paint and pipes were thought to be the main sources of lead exposure in the United States. However, consumer products, such as certain spices, ceramic and metal cookware, traditional health remedies, and cultural powders, are increasingly recognized as important sources of lead exposure across the United States.