tbuckley/cabot-search huggingface dataset:
Microbial Dark Matter: From Discovery to Applications
Authors: Yuguo Zha, Hui Chong, Pengshuo Yang, Kang Ning
Journal: Genomics Proteomics & Bioinformatics (2022)

With the rapid increase of the microbiome samples and sequencing data, more and more knowledge about microbial communities has been gained. However, there is still much more to learn about microbial communities, including billions of novel species and genes, as well as countless spatiotemporal dynamic patterns within the microbial communities, which together form the microbial dark matter. In this work, we summarized the dark matter in microbiome research and reviewed current data mining methods, especially artificial intelligence (AI) methods, for different types of knowledge discovery from microbial dark matter. We also provided case studies on using AI methods for microbiome data mining and knowledge discovery. In summary, we view microbial dark matter not as a problem to be solved but as an opportunity for AI methods to explore, with the goal of advancing our understanding of microbial communities, as well as developing better solutions to global concerns about human health and the environment.
Aqp2+ Progenitor Cells Maintain and Repair Distal Renal Segments
Authors: Chao Gao, Long Zhang, Enuo Chen, Wenzheng Zhang
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement Whether adult mammalian kidneys harbor progenitor cells is a long debated issue. Here we provide convincing and conclusive data demonstrating that cells expressing Aqp2 and V-ATPase subunits B1 and B2, like their embryonic and neonate counterparts, function as Aqp2 + progenitor cells (APs) in the adult mouse kidney, and play a critical role in the maintenance and regeneration of the kidney under normal and pathologic conditions (unilateral ureteral obstruction). APs may be considered the first potential candidate that meet the strict definition of progenitor cells requiring in vivo demonstration of self-renewal, clonogenicity, multipotency, and participation in maintenance and repair. Adult progenitor cells could become critical for regenerative medicine and response to diseases. Identification of APs and characterization of their role in renal maintenance and regeneration after renal injury may help in vitro kidney organoid generation. Background Adult progenitor cells presumably demonstrate clonogenicity, self-renewal, and multipotentiality, and can regenerate cells under various conditions. Definitive evidence demonstrating the existence of such progenitor cells in adult mammalian kidneys is lacking. Method We performed in vivo lineage tracing and thymidine analogue labeling using adult tamoxifen-inducible ( Aqp2ECE/+ RFP/+ , Aqp2ECE/+ Brainbow/+ , and Aqp2ECE/+ Brainbow/Brainbow ) and WT mice. The tamoxifen-inducible mice were analyzed between 1 and 300 days postinduction. Alternatively, WT and tamoxifen-induced mice were subjected to unilateral ureteral obstruction and thymidine analogue labeling and analyzed 2–14 days post-surgery. Multiple cell-specific markers were used for high-resolution immunofluorescence confocal microscopy to identify the cell types derived from Aqp2 + cells. Results Like their embryonic counterparts, adult cells expressing Aqp2 and V-ATPase subunits B1 and B2 (Aqp2 + B1B2 + ) are the potential Aqp2 + progenitor cells (APs). Adult APs rarely divide to generate daughter cells, either maintaining the property of the AP (self-renewal) or differentiating into DCT2/CNT/CD cells (multipotentiality), forming single cell–derived, multiple-cell clones (clonogenicity) during tissue maintenance. APs selectively and continuously regenerate DCT2/CNT/CD cells in response to injury resulting from ureteral ligation. AP proliferation demonstrated direct correlation with Notch activation and was inversely correlated with development of kidney fibrosis. Derivation of both intercalated and DCT2 cells was found to be cell division–dependent and –independent, most likely through AP differentiation which requires cell division and through direct conversion of APs and/or regular principal cells without cell division, respectively. Conclusion Our study demonstrates that Aqp2 + B1B2 + cells behave as adult APs to maintain and repair DCT2/CNT1/CNT2/CD segments.
Biomarker Development: Bedside to Bench
Authors: Grace E. Mishkin, Elise C. Kohn
Journal: Clinical Cancer Research (2022)

Summary This commentary complements the report from Nixon and colleagues by addressing the critical definitions, assay and analytical quality control and interpretation, and resources available to advance similar fit-for-purpose biomarker development. See related articles by Nixon et al., p. 2771 and 2779
Mobile Nanobots for Prevention of Root Canal Treatment Failure
Authors: Debayan Dasgupta, Shanmukh Peddi, Deepak Kumar Saini, Ambarish Ghosh
Journal: Advanced Healthcare Materials (2022)

Millions of root canal treatments fail worldwide due to remnant bacteria deep in the dentinal tubules located within the dentine tissue of human teeth. The complex and narrow geometry of the tubules renders current techniques relying on passive diffusion of antibacterial agents ineffective. Here, the potential of actively maneuvered nanobots is investigated to disinfect dentinal tubules, which can be incorporated during a standard root canal procedure. It is demonstrated that magnetically driven nanobots can reach the depths of the tubules not possible with current clinical practices. Subtle alterations of the magnetic drive allow both deep implantations of the nanobots isotopically distributed throughout the dentine and spatially controlled recovery from selected regions, further supported by numerical simulations. Finally, the integration of bactericidal therapeutic modality with the nanobots is demonstrated, thereby validating the tremendous potential of nanobots in dentistry and nanomedicine in general.
Analysis of Firearm Violence During the COVID-19 Pandemic in the US
Authors: Shengzhi Sun, Wangnan Cao, Yang Ge, Michael Siegel, Gregory A. Wellenius
Journal: JAMA Network Open (2022)

In the US, the COVID-19 pandemic intensified some conditions that may contribute to firearm violence, and a recent surge in firearm sales during the pandemic has been reported. However, patterns of change in firearm violence in the first year of the COVID-19 pandemic in the US remain unclear.To quantify the changes in interpersonal firearm violence associated with the pandemic across all 50 US states and the District of Columbia.This population-based cross-sectional study examined 50 US states and the District of Columbia from January 1, 2016, to February 28, 2021. The COVID-19 pandemic period was defined as between March 1, 2020, and February 28, 2021. Statistical analysis was performed from April to December 2021.A 2-stage interrupted time-series design was used to examine the excess burden of firearm-related incidents, nonfatal injuries, and deaths associated with the pandemic while accounting for long-term trends and seasonality. In the first stage, separate quasi-Poisson regression models were fit to the daily number of firearm events in each state. In the second stage, estimates were pooled using a multivariate meta-analysis.In the US (all 50 states and the District of Columbia) during the pandemic period of March 1, 2020, to February 28, 2021, there were 62 485 identified firearm-related incidents, 40 021 firearm-related nonfatal injuries, and 19 818 firearm-related deaths. The pandemic period was associated with 8138 (95% empirical confidence interval [eCI], 2769-12 948) excess incidents (increase of 15.0% [95% eCI, 4.6%-26.1%]), 10 222 (95% eCI, 8284-11 650) excess nonfatal injuries (increase of 34.3% [95% eCI, 26.1%-41.1%]), and 4381 (95% eCI, 2262-6264) excess deaths (increase of 28.4% [95% eCI, 12.9%-46.2%]). The increase in firearm-related violence was more pronounced from June to October 2020 and in Minnesota and New York State.In the US, the first year of the COVID-19 pandemic was associated with an excess burden of firearm-related incidents, nonfatal injuries, and deaths, with substantial temporal and spatial variations.
Surface Modification of Poly(ether ether ketone) by Simple Chemical Grafting of Strontium Chondroitin Sulfate to Improve its Anti‐Inflammation, Angiogenesis, Osteogenic Properties
Authors: Zhe Zheng, Liqiu Hu, Yongmei Ge, Jianchao Qi, Qili Sun, Zhenjian Li, Lijun Lin, Bin Tang
Journal: Advanced Healthcare Materials (2022)

Besides inducing osteogenic differentiation, the surface modification of poly(ether ether ketone) (PEEK) is highly expected to improve its angiogenic activity and reduce the inflammatory response in the surrounding tissue. Herein, strontium chondroitin sulfate is first attempted to be introduced into the surface of sulfonated PEEK (SPEEK-CS@Sr) based on the Schiff base reaction between PEEK and ethylenediamine (EDA) and the amidation reaction between EDA and chondroitin sulfate (CS). The surface characteristics of SPEEK-CS@Sr implant are systematically investigated, and its biological properties in vitro and in vivo are also evaluated. The results show that the surface of SPEEK-CS@Sr implant exhibits a 3D microporous structure and good hydrophilicity, and can steadily release Sr ions. Importantly, the SPEEK-CS@Sr not only displays excellent biocompatibility, but also can remarkably promote cell adhesion and spread, improve osteogenic activity and angiogenic activity, and reduce the inflammatory response compared to the original PEEK. Therefore, this study presents the surface modification of PEEK material by simple chemical grafting of strontium chondroitin sulfate to improve its angiogenesis, anti-inflammation, and osteogenic properties, and the as-fabricated SPEEK-CS@Sr has the potential to serve as a promising orthopedic implant in bone tissue engineering.
Early increases in anti-SARS-CoV-2 antibody isotypes associated with organ dysfunction and mortality in patients hospitalized with COVID-19
Authors: John R. Best, Meng Wang, Terry Lee, James A. Russell, Mari L. DeMarco, Taylor D. Pobran, Terry Lee, Matthew P. Cheng, Karen Tran, David Sweet, John Marshall, Arthur S. Slutsky, Srinivas Murthy, Joel Singer, David M. Patrick, Todd C. Lee, John H. Boyd, Keith R. Walley, Francois Lamontagne, Robert Fowler, Brent W. Winston, Greg Haljan, Donald C. Vinh, Alison McGeer, David Maslove, Puneet Mann, Kathryn Donohoe, Geraldine Hernandez, Anita Palep
Journal: Intensive Care Medicine (2022)
A multi-organ chip with matured tissue niches linked by vascular flow
Authors: Kacey Ronaldson-Bouchard, Diogo Teles, Keith Yeager, Daniel Naveed Tavakol, Yimu Zhao, Alan Chramiec, Somnath Tagore, Max Summers, Sophia Stylianos, Manuel Tamargo, Busub Marcus Lee, Susan P. Halligan, Erbil Hasan Abaci, Zongyou Guo, Joanna Jacków, Alberto Pappalardo, Jerry Shih, Rajesh K. Soni, Shivam Sonar, Carrie German, Angela M. Christiano, Andrea Califano, Karen K. Hirschi, Christopher S. Chen, Andrzej Przekwas, Gordana Vunjak-Novakovic
Journal: Nature Biomedical Engineering (2022)
Whole-genome sequencing reveals complex genomic features underlying anti-CD19 CAR T-cell treatment failures in lymphoma
Authors: Michael D. Jain, Bachisio Ziccheddu, Caroline A. Coughlin, Rawan Faramand, Anthony J. Griswold, Kayla M. Reid, Meghan Menges, Yonghong Zhang, Ling Cen, Xuefeng Wang, Mohammad Hussaini, Ola Landgren, Marco L. Davila, Jonathan H. Schatz, Frederick L. Locke, Francesco Maura
Journal: Blood (2022)
Food craving-like episodes during pregnancy are mediated by accumbal dopaminergic circuits
Authors: Roberta Haddad-Tóvolli, Sara Ramírez, Emma Muñoz-Moreno, Maria Milà-Guasch, Lluis Miquel-Rio, Macarena Pozo, Iñigo Chivite, Jordi Altirriba, Arnaud Obri, Alicia Gómez-Valadés, Miriam Toledo, Elena Eyre, Analia Bortolozzi, Emmanuel Valjent, Guadalupe Soria, Marc Claret
Journal: Nature Metabolism (2022)
MiRNA-363-3p/DUSP10/JNK axis mediates chemoresistance by enhancing DNA damage repair in diffuse large B-cell lymphoma
Authors: Wenping Zhou, Yuanlin Xu, Jiuyang Zhang, Peipei Zhang, Zhihua Yao, Zheng Yan, Haiying Wang, Junfeng Chu, Shuna Yao, Shuang Zhao, Shujun Yang, Yongjun Guo, Jinxin Miao, Kangdong Liu, Wing C. Chan, Qingxin Xia, Yanyan Liu
Journal: Leukemia (2022)

Abstract Anthracycline-based chemotherapy resistance represents a major challenge in diffuse large B-cell lymphoma (DLBCL). MiRNA and gene expression profiles ( n = 47) were determined to uncover potential chemoresistance mechanisms and therapeutic approaches. An independent correlation between high expression of miRNA-363-3p and chemoresistance was observed and validated in a larger cohort ( n = 106). MiRNA-363-3p was shown to reduce doxorubicin-induced apoptosis and tumor shrinkage in in vitro and in vivo experiments by ectopic expression and CRISPR/Cas9-mediated knockout in DLBCL cell lines. DNA methylation was found to participate in transcriptional regulation of miRNA-363-3p. Further investigation revealed that dual specificity phosphatase 10 (DUSP10) is a target of miRNA-363-3p and its suppression promotes the phosphorylation of c-Jun N-terminal kinase (JNK). The miRNA-363-3p/DUSP10/JNK axis was predominantly associated with negative regulation of homologous recombination (HR) and DNA repair pathways. Ectopic expression of miRNA-363-3p more effectively repaired doxorubicin-induced double-strand break (DSB) while enhancing non-homologous end joining repair and reducing HR repair. Targeting JNK and poly (ADP-ribose) polymerase 1 significantly inhibited doxorubicin-induced DSB repair, increased doxorubicin-induced cell apoptosis and tumor shrinkage, and improved the survival of tumor-bearing mice. In conclusion, the miRNA-363-3p/DUSP10/JNK axis is a novel chemoresistance mechanism in DLBCL that may be reversed by targeted therapy.
Author Correction: Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
Authors: Emma Nolan, Victoria Louise Bridgeman, Luigi Ombrato, Adam Karoutas, Nicolas Rabas, Celine Angeli Natascha Sewnath, Marcos Vasquez, Felipe Silva Rodrigues, Stuart Horswell, Peter Faull, Rebecca Carter, Ilaria Malanchi
Journal: Nature Cancer (2022)
Interleukin-33 antibody failed to demonstrate benefit in a phase II, double-blind, randomized, placebo-controlled study in adult patients with moderate-to-severe atopic dermatitis
Authors: Vivian Laquer, Viviana Parra, Jean-Philippe Lacour, Hidetoshi Takahashi, Jack Knorr, Angela J. Okragly, Douglas E. James, Jonathan T. Sims, Ching-Yun Chang, Jeannie Chao, Paul Klekotka
Journal: British Journal of Dermatology (2022)

Dear Editor, therapeutic intervention for atopic dermatitis (AD) focuses on neutralizing effector cytokines such as interleukin (IL)‐4 and IL‐13·1,2 IL‐33 is a driver of T helper (Th)2‐mediated inflammation and is upstream of IL‐4 and IL‐13. AD lesional skin includes more IL‐33‐expressing cells than nonlesional skin,3 while serum levels of IL‐33 are reported to be sevenfold higher in patients with AD than in healthy control participants and correlated with disease severity·4 This and proof of concept data led to the hypothesis that an anti‐IL‐33 antibody could be efficacious for the treatment of AD·5 This phase II, randomized, double‐blind, placebo‐controlled study (NCT03831191) aimed to evaluate the safety and efficacy of LY3375880, a human IgG4‐variant monoclonal antibody that binds and neutralizes soluble human IL‐33, in patients with moderate‐to‐severe AD. Investigators evaluated patients in 58 centres in nine countries in Asia, Europe, South America, and North America. Patients [Validated Investigator's Global Assessment ‐ Atopic Dermatitis (vIGA‐AD) score of ≥ 3 and an inadequate response to topical medications] were stratified according to disease severity (vIGA‐AD 3 vs. 4) and geographic region (Japan vs. non‐Japan) and randomized to receive subcutaneous injections of placebo or LY3375880 (50, 150 or 600 mg) (1: 1: 1: 1 ratio using an interactive web‐response system) every 4 weeks for 16 weeks. The primary outcome sought was the proportion of patients achieving vIGA‐AD of 0 or 1 with a ≥ 2‐point improvement at week 16. An internal assessment committee conducted an unblinded interim analysis of efficacy and safety data when one‐third of patients had completed 16 weeks of treatment or discontinued.
Biological impact of iberdomide in patients with active systemic lupus erythematosus
Authors: Peter E Lipsky, Ronald van Vollenhoven, Thomas Dörner, Victoria P Werth, Joan T Merrill, Richard Furie, Milan Petronijevic, Benito Velasco Zamora, Maria Majdan, Fedra Irazoque-Palazuelos, Robert Terbrueggen, Nikolay Delev, Michael Weiswasser, Shimon Korish, Mark Stern, Sarah Hersey, Ying Ye, Allison Gaudy, Zhaohui Liu, Robert Gagnon, Shaojun Tang, Peter H Schafer
Journal: Annals of the Rheumatic Diseases (2022)

Iberdomide is a high-affinity cereblon ligand that promotes proteasomal degradation of transcription factors Ikaros (
Trapping of CDC42 C-terminal variants in the Golgi drives pyrin inflammasome hyperactivation
Authors: Masahiko Nishitani-Isa, Kojiro Mukai, Yoshitaka Honda, Hiroshi Nihira, Takayuki Tanaka, Hirofumi Shibata, Kumi Kodama, Eitaro Hiejima, Kazushi Izawa, Yuri Kawasaki, Mitsujiro Osawa, Yu Katata, Sachiko Onodera, Tatsuya Watanabe, Takashi Uchida, Shigeo Kure, Junko Takita, Osamu Ohara, Megumu K. Saito, Ryuta Nishikomori, Tomohiko Taguchi, Yoji Sasahara, Takahiro Yasumi
Journal: The Journal of Experimental Medicine (2022)

Mutations in the C-terminal region of the CDC42 gene cause severe neonatal-onset autoinflammation. Effectiveness of IL-1β–blocking therapy indicates that the pathology involves abnormal inflammasome activation; however, the mechanism underlying autoinflammation remains to be elucidated. Using induced-pluripotent stem cells established from patients carrying CDC42R186C, we found that patient-derived cells secreted larger amounts of IL-1β in response to pyrin-activating stimuli. Aberrant palmitoylation and localization of CDC42R186C protein to the Golgi apparatus promoted pyrin inflammasome assembly downstream of pyrin dephosphorylation. Aberrant subcellular localization was the common pathological feature shared by CDC42 C-terminal variants with inflammatory phenotypes, including CDC42*192C*24 that also localizes to the Golgi apparatus. Furthermore, the level of pyrin inflammasome overactivation paralleled that of mutant protein accumulation in the Golgi apparatus, but not that of the mutant GTPase activity. These results reveal an unexpected association between CDC42 subcellular localization and pyrin inflammasome activation that could pave the way for elucidating the mechanism of pyrin inflammasome formation.
Overexpression of the energy metabolism transcriptome within clonal plasma cells is associated with the pathogenesis and outcomes of patients with multiple myeloma
Authors: Laura A. Evans, Emilie A. Anderson, Erik Jessen, Bharat Nandakumar, Ezgi Atilgan, Dragan Jevremovic, Taro Hitosugi, Rafael Fonseca, Shaji K. Kumar, Wilson I. Gonsalves
Journal: American Journal of Hematology (2022)

Altered energy metabolism and changes in glycolytic and oxidative phosphorylation pathways are hallmarks of all cancer cells. The expression of select genes associated with the production of various enzymes and proteins involved in glycolysis and oxidative phosphorylation were assessed in the clonal plasma cells derived from patients with newly diagnosed multiple myeloma (NDMM) enrolled in the Multiple Myeloma Research Foundation (MMRF) CoMMpass data set. A scoring system consisting of assigning a point for every gene where their fragments per kilobase of transcript per million (FPKM) was above the median yielded a minimum of 0 and a maximum of 12 for the set of genes in the glycolytic and oxidative phosphorylation pathways to create a total energy metabolism molecular signature (EMMS) score. This EMMS score was independently associated with worse progression free survival (PFS) and overall survival (OS) outcomes of patients with NDMM. A higher EMMS score was more likely to be present in clonal plasma cells derived from Multiple myeloma (MM) patients than those from patients with monoclonal gammopathy of undetermined significance (MGUS). This was functionally confirmed by the clonal plasma cells from MM patients having a higher rate of mitochondrial and glycolysis-derived ATP formation than clonal plasma cells from MGUS patients. Thus, this study provides evidence for the effect of energy metabolism within clonal plasma cells on pathogenesis and outcomes of patients with MM. Exploiting the energy-producing metabolic pathways within clonal plasma cells for diagnostic and therapeutic purposes in MM should be explored in the future.
Racial and Ethnic Disparities in Insurance Coverage Among US Adults Aged 60 to 64 Years
Authors: Anna Patterson, Taylor J. Robinson, Eric T. Roberts
Journal: JAMA Network Open (2022)

We analyzed the 2019 American Community Survey, which reports demographic, residential, and insurance information.We used self-reported race and ethnicity to categorize respondents as Black, Hispanic, or White.The University of Pittsburgh institutional review board waived study review and informed consent because this analysis used deidentified data.We followed Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.We conducted 2 analyses of uninsurance and racial and ethnic coverage disparities among adults aged 60 to 64 years, illustrating potential for near-universal Medicare coverage to reduce these disparities.First, we estimated national and state-level uninsured rates among Black and Hispanic adults of all incomes.We estimated state-level rates by fitting linear regression models estimating uninsurance as a function of state fixed effects.Second, among adults with incomes less than 138% FPL, we compared Black-White and Hispanic-White disparities in uninsurance between Medicaid expansion and nonexpansion states by fitting linear models to estimate uninsurance as a function of expansion status, race and ethnicity, and the interaction of these variables.All models adjusted for sex, marital status, employment status income, disability, and used ACS survey weights (eAppendix in the Supplement).Expansion status was assessed as of December 31, 2019. ResultsAmong US adults aged 60 to 64 years, 52.1% (95% CI, 52.0%-52.4%)were female, 12.3% (95% CI, 12.1%-12.5%)were Black, 11.6% (95% CI, 11.4%-11.8%)were Hispanic, and 76.1% (95% CI, 75.9%-76.4%)were White.Among adults aged 60 to 64 years who were uninsured in 2019 across all states and income levels, 6.9% (95% CI, 5.8%-8.0%)were Black, 15.1% (95% CI, 11.1%-19.2%)were
Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma—Challenges and Potential Solutions
Authors: Samer Al Hadidi, Maurizio Zangari, Frits van Rhee
Journal: JAMA Oncology (2022)

This Viewpoint discusses the multiple challenges that face patients and their treating oncologists when considering patients for chimeric antigen receptor T-cell therapy and assesses potential solutions.