tbuckley/cabot-search huggingface dataset:
Benefits and Risks of Iron Interventions in Infants in Rural Bangladesh
Authors: Sant-Rayn Pasricha, M. Imrul Hasan, Sabine Braat, Leila M. Larson, S.M. Mulk-Uddin Tipu, Sheikh J. Hossain, Shamima Shiraji, Andrew Baldi, Mohammad S.A. Bhuiyan, Fahmida Tofail, Jane Fisher, Sally Grantham-McGregor, Julie A. Simpson, Jena D. Hamadani, Beverley-Ann Biggs
Journal: New England Journal of Medicine (2021)

Universal provision of iron supplements (drops or syrup) or multiple micronutrient powders to young children in low-to-middle-income countries where anemia is prevalent is recommended by the World Health Organization and widely implemented. The functional benefits and safety of these interventions are unclear.
CD4+ T cell-mimicking nanoparticles encapsulating DIABLO/SMAC mimetics broadly neutralize HIV-1 and selectively kill HIV-1-infected cells
Authors: Grant R Campbell, Jia Zhuang, Gang Zhang, Igor Landa, Luke J Kubiatowicz, Diana Dehaini, Ronnie H Fang, Liangfang Zhang, Stephen A Spector
Journal: Theranostics (2021)

HIV-1 is a major global health challenge. The development of an effective vaccine and a therapeutic cure are top priorities. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 stymies this progress. Therapeutic strategies that provide effective and broad-spectrum neutralization against HIV-1 infection are highly desirable. Methods: We investigated the potential of nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP) encapsulating the DIABLO/SMAC mimetics LCL-161 or AT-406 (also known as SM-406 or Debio 1143) to both neutralize HIV-1 and selectively kill HIV-1-infected resting CD4+ T cells and macrophages. Results: DIABLO/SMAC mimetic-loaded TNP displayed outstanding neutralizing breadth and potency, and selectively kill HIV-1-infected cells via autophagy-dependent apoptosis while having no drug-induced off-target or cytotoxic effects on bystander cells. Genetic inhibition of early stages of autophagy abolishes this effect. Conclusion: DIABLO/SMAC mimetic loaded TNP have the potential to be used as therapeutic agents to neutralize cell-free HIV-1 and to kill specifically HIV-1-infected cells as part of an HIV-1 cure strategy.
SNAI2-Mediated Repression of <i>BIM</i> Protects Rhabdomyosarcoma from Ionizing Radiation
Authors: Long Wang, Nicole R. Hensch, Kathryn Bondra, Prethish Sreenivas, Xiang R. Zhao, Jiangfei Chen, Rodrigo Moreno Campos, Kunal Baxi, Angelina V. Vaseva, Benjamin D. Sunkel, Berkley E. Gryder, Silvia Pomella, Benjamin Z. Stanton, Siyuan Zheng, Eleanor Y. Chen, Rossella Rota, Javed Khan, Peter J. Houghton, Myron S. Ignatius
Journal: Cancer Research (2021)

Abstract Ionizing radiation (IR) and chemotherapy are mainstays of treatment for patients with rhabdomyosarcoma, yet the molecular mechanisms that underlie the success or failure of radiotherapy remain unclear. The transcriptional repressor SNAI2 was previously identified as a key regulator of IR sensitivity in normal and malignant stem cells through its repression of the proapoptotic BH3-only gene PUMA/BBC3. Here, we demonstrate a clear correlation between SNAI2 expression levels and radiosensitivity across multiple rhabdomyosarcoma cell lines. Modulating SNAI2 levels in rhabdomyosarcoma cells through its overexpression or knockdown altered radiosensitivity in vitro and in vivo. SNAI2 expression reliably promoted overall cell growth and inhibited mitochondrial apoptosis following exposure to IR, with either variable or minimal effects on differentiation and senescence, respectively. Importantly, SNAI2 knockdown increased expression of the proapoptotic BH3-only gene BIM, and chromatin immunoprecipitation sequencing experiments established that SNAI2 is a direct repressor of BIM/BCL2L11. Because the p53 pathway is nonfunctional in the rhabdomyosarcoma cells used in this study, we have identified a new, p53-independent SNAI2/BIM signaling axis that could potentially predict clinical responses to IR treatment and be exploited to improve rhabdomyosarcoma therapy. Significance: SNAI2 is identified as a major regulator of radiation-induced apoptosis in rhabdomyosarcoma through previously unknown mechanisms independent of p53.
Medial Arterial Calcification
Authors: Peter Lanzer, Fadil M. Hannan, Jan D. Lanzer, Jan Janzen, Paolo Raggi, Dominic Furniss, Mirjam Schuchardt, Rajesh Thakker, Pak-Wing Fok, Julio Saez-Rodriguez, Angel Millan, Yu Sato, Roberto Ferraresi, Renu Virmani, Cynthia St. Hilaire
Journal: Journal of the American College of Cardiology (2021)
Full-field stimulus testing: Role in the clinic and as an outcome measure in clinical trials of severe childhood retinal disease
Authors: Alejandro J. Roman, Artur V. Cideciyan, Vivian Wu, Alexandra V. Garafalo, Samuel G. Jacobson
Journal: Progress in Retinal and Eye Research (2021)

Disease mechanisms have become better understood in previously incurable forms of early-onset severe retinal dystrophy, such as Leber congenital amaurosis (LCA). This has led to novel treatments and clinical trials that have shown some success. Standard methods to measure vision were difficult if not impossible to perform in severely affected patients with low vision and nystagmus. To meet the need for visual assays, we devised a psychophysical method, which we named full-field stimulus testing (FST). From early versions based on an automated perimeter, we advanced FST to a more available light-emitting diode platform. The journey from invention to use of such a technique in our inherited retinal degeneration clinic is reviewed and many of the lessons learned over the 15 years of application of FST are explained. Although the original purpose and application of FST was to quantify visual thresholds in LCA, there are rare opportunities for FST also to be used beyond LCA to measure aspects of vision in other inherited retinal degenerations; examples are given. The main goal of the current review, however, remains to enable investigators studying and treating LCA to understand how to best use FST and how to reduce artefact and confounding complexities so the test results become more valuable to the understanding of LCA diseases and results of novel interventions.
Peroxisome proliferator-activated receptor-γ signalling protects hair follicle stem cells from chemotherapy-induced apoptosis and epithelial–mesenchymal transition
Authors: I. Piccini, L. Brunken, J. Chéret, S. Ghatak, Y. Ramot, M. Alam, T.S. Purba, J. Hardman, H. Erdmann, F. Jimenez, R. Paus, M. Bertolini
Journal: British Journal of Dermatology (2021)

Permanent chemotherapy-induced alopecia (pCIA), for which preventive interventions remain limited, can manifest with scarring. While the underlying pathomechanisms of pCIA are unclear, depletion of epithelial hair follicle (HF) stem cells (eHFSCs) is likely to play a role.To explore the hypothesis that, besides apoptosis, eHFSCs undergo pathological epithelial-mesenchymal transition (EMT) in pCIA, thus explaining the scarring phenotype. Furthermore, we tested whether a peroxisome proliferator-activated receptor (PPAR)-γ modulator could prevent pCIA-associated pathomechanisms.Organ-cultured human scalp HFs were treated with the cyclophosphamide metabolite 4-hydroperoxycyclophosphamide (4-HC). Additionally, HFs were pretreated with the agonistic PPAR-γ modulator N-acetyl-GED-0507-34-Levo (NAGED), which has previously been shown to promote K15 expression and antagonize EMT in eHFSCs.In accordance with anticipated hair bulb cytotoxicity, dystrophy and catagen induction, 4-HC promoted apoptosis along with increased p53 expression, DNA damage and pathological EMT in keratin 15+ (K15) eHFSCs, as evidenced by decreased E-cadherin expression and the appearance of fibronectin+ and vimentin+ cells in the hair bulge. Pretreatment with NAGED protected against 4-HC-induced hair bulb cytotoxicity/dystrophy, and apoptosis, p53 upregulation and EMT in the bulge, thereby significantly preventing depletion of K15+ human eHFSCs ex vivo.Since a key cyclophosphamide metabolite alone suffices to damage and deplete human scalp eHFSCs by promoting apoptosis, DNA damage and EMT ex vivo, strategies to prevent pCIA need to target these pathomechanisms. Given the ability of NAGED to prevent chemotherapy-induced eHFSCs damage ex vivo, our study introduces the stimulation of PPAR-γ signalling as a novel intervention strategy for the prevention of pCIA.
Covid-19: “Health in all policies” will help protect world from future pandemics, says commission
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Health in all policies" will help protect world from future pandemics, says commission Zosia KmietowiczThe health of humans, other animals, plants, and the environment must be considered together by all agencies and in all policies to protect the planet from a future pandemic, an independent commission has recommended. 11 Pan-European Commission on Health and Sustainable Development.Drawing light from the pandemic: a new strategy for health and sustainable development.Sep 2021.https://www.euro.who.int/en/health-topics/healthpolicy/european-programme-of-work/pan-european-commission-on-healthand-sustainable-development/publications/drawing-
Long-Term Exposure to Ultrafine Particles and Particulate Matter Constituents and the Risk of Amyotrophic Lateral Sclerosis
Authors: Zhebin Yu, Susan Peters, Loes van Boxmeer, George S. Downward, Gerard Hoek, Marianthi-Anna Kioumourtzoglou, Marc G. Weisskopf, Johnni Hansen, Leonard H. van den Berg, Roel C.H. Vermeulen
Journal: Environmental Health Perspectives (2021)
Correction: Genomic analysis of cellular hierarchy in acute myeloid leukemia using ultrasensitive LC-FACSeq
Authors: Caner Saygin, Eileen Hu, Pu Zhang, Steven Sher, Arletta Lozanski, Tzyy-Jye Doong, Deedra Nicolet, Shelley Orwick, Jadwiga Labanowska, Jordan N. Skinner, Casey Cempre, Tierney Kauffman, Virginia M. Goettl, Nyla A. Heerema, Lynne Abruzzo, Cecelia Miller, Rosa Lapalombella, Gregory Behbehani, Alice S. Mims, Karilyn Larkin, Nicole Grieselhuber, Alison Walker, Bhavana Bhatnagar, Clara D. Bloomfield, John C. Byrd, Gerard Lozanski, James S. Blachly
Journal: Leukemia (2021)
CD34-positive staining in prostate biopsy specimens predicts a poor prognosis of prostate cancer together with mast cell infiltration
Authors: Norio Nonomura, Hitoshi Takayama, Yasutomo Nakai, Masashi Nakayama, Kazuo Nishimura, Masatoshi Mukai, Akira Nagahara, Daizo Oka, Masahiro Shiba, Hitoshi Inoue, Akira Tsujimura, Akihiko Okuyama
Journal: Cancer Research (2008)

5340  Introduction and objectives: Mast cells and macrophages infiltrating into cancer tissues have been reported to play some roles in cancer progression. Tumor-infiltrating mast cells have been reported to produce some angiogenic factors such as fibroblast growth factor (FGF)-2, vascular endothelial cell growth factor (VEGF), transforming growth factor (TGF)-β and interleukin (IL)-8. These factors are all involved in tumor-associated angiogenesis. For prostate cancer (PCA), prognostic significance of tumor-infiltrating innate immune cells has not been well studied yet. In the present study, we have examined the correlation between CD34-positive staining together with tumor-infiltrating mast cell count and the prognosis of PCA using the needle biopsy specimens.  Materials and methods: Cancer-positive needle biopsy specimens from 104 PCA patients were used for immunostaining. Biopsy specimens were immunohistochemically labeled for vascular endothelial cells with monoclonal (CD34) antibody and for tumor-infiltrating mast cells with monoclonal antibody against mast cell-specific tryptase. For systematic counting of tumor-infiltrating mast cells, 3 ocular measuring fields, each real area of 0.06175 mm2, were randomly chosen under a microscope at a power of x 400 within a cancer. CD34-positive cells were evaluated using an image-analyzing software.  Results: Median value of CD34-positive staining was 1.494. The prognosis of patients with higher CD34 levels was significantly worse than those with lower levels (p
Terpenoid treatment in osteoporosis: this is where we have come in research
Authors: Daniele Bellavia, Fabio Caradonna, Eufrosina Dimarco, Viviana Costa, Valeria Carina, Angela De Luca, Lavinia Raimondi, Carla Gentile, Riccardo Alessandro, Milena Fini, Gianluca Giavaresi
Journal: Trends in Endocrinology and Metabolism (2021)
Characterising normal patterns of alanine aminotransferase elevations in ursodeoxycholic acid-treated patients with primary biliary cholangitis
Authors: Antoine Sioufi, Carla Fiorella Murillo Perez, Frederik Nevens, Aliya F. Gulamhusein, Marco Carbone, Palak Trivedi, Adriaan J. Van der Meer, Christophe Corpechot, Pier M. Battezzati, Willem J. Lammers, Nora Cazzagon, Annarosa Floreani, Albert Pares, Anna Reig, Ana Lleo, Marlyn J. Mayo, Kris V. Kowdley, Cyriel Ponsioen, George N. Dalekos, Nikolaos K. Gatselis, Douglas Thorburn, Harry L. A. Janssen, Andrew L. Mason, Xavier Verhelst, Tony Bruns, Keith D. Lindor, Olivier Chazouilleres, Pietro Invernizzi, Bettina E. Hansen, Gideon M. Hirschfield
Journal: Hepatology (2020)
MicroRNA-23b-3p Deletion Induces an IgA Nephropathy-like Disease Associated with Dysregulated Mucosal IgA Synthesis
Authors: Hongzhi Li, Zhichao Chen, Weitian Chen, Jingyi Li, Yunshuang Liu, Hongchuang Ma, Mingming Shi, Xuelian Sun, Xiusong Yao, Zhijun Li, Izabella Z.A Pawluczyk, Shuchen Zhang, Jonathan Barratt, Jicheng Lv, Kai Wang, Binghai Zhao
Journal: Journal of the American Society of Nephrology (2021)

IgA nephropathy (IgAN) is the most common primary GN worldwide. Circulating immune complexes form that are prone to deposition in the mesangium, where they trigger glomerular inflammation. A growing body of evidence suggests that dysregulated expression of microRNAs in IgAN may play a significant role in establishing the disease phenotype.We generated single miR-23b-3p(miR-23b) knockout mice using CRISPR-Cas9.In humans, miR-23b levels are downregulated in kidney biopsies and sera of patients with IgAN, and serum miR-23b levels are negatively correlated with serum IgA1 levels. We show that miR-23b-/- mice develop an IgAN-like phenotype of mesangial IgA and C3 deposition associated with development of albuminuria, hypertension, an elevated serum creatinine, and dysregulated mucosal IgA synthesis. Dysregulation of IgA production is likely mediated by the loss of miR-23b-mediated suppression of activation-induced cytidine deaminase in mucosal B cells. In addition, we show that loss of miR-23b increases the susceptibility of the kidney to progressive fibrosis through loss of regulation of expression of gremlin 2 and IgA accumulation through downregulation of the transferrin receptor.Our findings suggest an indispensable role for miR-23b in kidney disease, and in particular, IgAN. miR-23b may in the future offer a novel therapeutic target for the treatment of IgAN.
Association of Atopic Dermatitis and Mental Health Outcomes Across Childhood
Authors: Chloe Kern, Joy Wan, Kaja Z. LeWinn, Faustine D. Ramirez, Yong Lee, Charles E. McCulloch, Sinéad M. Langan, Katrina Abuabara
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Research has highlighted associations between atopic dermatitis (AD) and mental health conditions in adults. However, literature on the development of mental health comorbidities in children is limited despite the large burden of pediatric AD worldwide. <h3>Objective</h3> To examine the association between AD and internalizing behaviors and symptoms of depression at multiple points across childhood and adolescence and to explore potential mediating factors, including asthma/rhinitis, sleep, and inflammation. <h3>Design, Setting, and Participants</h3> This longitudinal, population-based birth cohort study included children followed up from birth for a mean (SD) duration of 10.0 (2.9) years from the UK Avon Longitudinal Study of Parents and Children. Data were collected from September 6, 1990, to December 31, 2009. Data were analyzed from August 30, 2019, to July 30, 2020. <h3>Exposures</h3> Annual period prevalence of AD assessed at 11 points from 6 months to 18 years of age, measured by standardized questions about flexural dermatitis. <h3>Main Outcomes and Measures</h3> Symptoms of depression, measured using child-reported responses to the Short Moods and Feelings Questionnaire at 5 points from 10 to 18 years of age and internalizing behaviors, measured by maternal report of the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire at 7 points from 4 to 16 years of age. <h3>Results</h3> Among the 11 181 children included in the analysis (5721 male [51.2%]), the period prevalence of symptoms of depression ranged from 6.0% to 21.6%; for internalizing behaviors, from 10.4% to 16.0%. Although mild to moderate AD was not associated with symptoms of depression, it was associated with internalizing behaviors as early as 4 years of age (mean increased odds of 29%-84% across childhood in adjusted models). Severe AD was associated with symptoms of depression (adjusted odds ratio, 2.38; 95% CI, 1.21-4.72) and internalizing symptoms (adjusted odds ratio, 1.90; 95% CI, 1.14-3.16). Sleep quality mediated some of this association, but it was not explained by differences in sleep duration, asthma/rhinitis, or levels of inflammatory markers (interleukin 6 and C-reactive protein). <h3>Conclusions and Relevance</h3> Within this population-based birth cohort study in the UK, severe AD was associated with symptoms of depression and internalizing behaviors throughout childhood and adolescence. Risk of internalizing symptoms was increased even for children with mild AD beginning early in childhood, highlighting the importance of behavioral and mental health awareness in this population.
H2A ubiquitination is essential for Polycomb Repressive Complex 1-mediated gene regulation in Marchantia polymorpha
Authors: Shujing Liu, Minerva S. Trejo-Arellano, Yichun Qiu, D. Magnus Eklund, Claudia Köhler, Lars Hennig
Journal: Genome biology (2021)

Abstract Background Polycomb repressive complex 1 (PRC1) and PRC2 are chromatin regulators maintaining transcriptional repression. The deposition of H3 lysine 27 tri-methylation (H3K27me3) by PRC2 is known to be required for transcriptional repression, whereas the contribution of H2A ubiquitination (H2Aub) in the Polycomb repressive system remains unclear in plants. Results We directly test the requirement of H2Aub for gene regulation in Marchantia polymorpha by generating point mutations in H2A that prevent ubiquitination by PRC1. These mutants show reduced H3K27me3 levels on the same target sites as mutants defective in PRC1 subunits MpBMI1 and the homolog MpBMI1L, revealing that PRC1-catalyzed H2Aub is essential for Polycomb system function. Furthermore, by comparing transcriptome data between mutants in MpH2A and MpBMI1/1L, we demonstrate that H2Aub contributes to the PRC1-mediated transcriptional level of genes and transposable elements. Conclusion Together, our data demonstrates that H2Aub plays a direct role in H3K27me3 deposition and is required for PRC1-mediated transcriptional changes in both genes and transposable elements in Marchantia .
Enhanced chemo-photodynamic therapy of an enzyme-responsive prodrug in bladder cancer patient-derived xenograft models
Authors: Ping Tan, Hao Cai, Qiang Wei, Xiaodi Tang, Qianfeng Zhang, Michal Kopytynski, Junxiao Yang, Yong Yi, Hu Zhang, Qiyong Gong, Zhongwei Gu, Rongjun Chen, Kui Luo
Journal: Biomaterials (2021)
P-100 A phase II study of first-line chemotherapy initiating FOLFIRI+cetuximab and switching to FOLFIRI+bevacizumab according to early tumor shrinkage at 8 weeks in RAS wild-type metastatic colorectal cancer: HYBRID trial
Authors: H. Shoji, T. Tsuda, M. Shimokawa, K. Akiyoshi, S. Tokunaga, K. Kunieda, M. Kotaka, T. Matsumoto, Y. Nagata, T. Mizukami, F. Mizuki, K. Danenberg, Y. Sunakawa, N. Boku, T. Nakajima
Journal: Annals of Oncology (2021)
Protein degradation technology: a strategic paradigm shift in drug discovery
Authors: Haobin Li, Jinyun Dong, Maohua Cai, Zhiyuan Xu, Xiang-Dong Cheng, Jiang-Jiang Qin
Journal: Journal of Hematology & Oncology (2021)

Abstract Targeting pathogenic proteins with small-molecule inhibitors (SMIs) has become a widely used strategy for treating malignant tumors. However, most intracellular proteins have been proven to be undruggable due to a lack of active sites, leading to a significant challenge in the design and development of SMIs. In recent years, the proteolysis-targeting chimeric technology and related emerging degradation technologies have provided additional approaches for targeting these undruggable proteins. These degradation technologies show a tendency of superiority over SMIs, including the rapid and continuous target consumption as well as the stronger pharmacological effects, being a hot topic in current research. This review mainly focuses on summarizing the development of protein degradation technologies in recent years. Their advantages, potential applications, and limitations are also discussed. We hope this review would shed light on the design, discovery, and clinical application of drugs associated with these degradation technologies.
The psychobiological links between chronic stress‐related diseases, periodontal/peri‐implant diseases, and wound healing
Authors: Ann M. Decker, Yvonne L. Kapila, Hom‐Lay Wang
Journal: Periodontology 2000 (2021)

Chronic stress is a relevant disease to periodontal practice, encompassing 25%-28% of the US population (American Psychological Association 2015). While it is well established that chronic psychologic stress can have significant deleterious systemic effects, only in recent decades have we begun to explore the biochemical, microbial, and physiologic impacts of chronic stress diseases on oral tissues. Currently, chronic stress is classified as a "risk indicator" for periodontal disease. However, as the evidence in this field matures with additional clinically controlled trials, more homogeneous data collection methods, and a better grasp of the biologic underpinnings of stress-mediated dysbiosis, emerging evidence suggests that chronic stress and related diseases (depression, anxiety) may be significant contributing factors in periodontal/peri-implant disease progression and inconsistent wound healing following periodontal-related therapeutics. Ideal solutions for these patients include classification of the disease process and de-escalation of chronic stress conditions through coping strategies. This paper also summarizes periodontal/implant-related therapeutic approaches to ensure predictable results for this specific patient subpopulation.
Characteristics of SARS-CoV-2 Infections in Israeli Children During the Circulation of Different SARS-CoV-2 Variants
Authors: Ido Somekh, Michal Stein, Isabella Karakis, Eric A. F. Simões, Eli Somekh
Journal: JAMA Network Open (2021)

This cohort study compares the characteristics of infections from SARS-CoV-2 variants spreading during August to October 2020 vs the variants spreading during December 2020 to February 2021 among children in Israel.