tbuckley/cabot-search huggingface dataset:
The association between heat exposure and hospitalization for undernutrition in Brazil during 2000−2015: A nationwide case-crossover study
Authors: Rongbin Xu, Qi Zhao, Micheline S. Z. S. Coelho, Paulo H. N. Saldiva, Michael J. Abramson, Shanshan Li, Yuming Guo
Journal: PLoS Medicine (2019)

Background Global warming is predicted to indirectly result in more undernutrition by threatening crop production. Whether temperature rise could affect undernutrition directly is unknown. We aim to quantify the relationship between short-term heat exposure and risk of hospitalization due to undernutrition in Brazil. Methods and findings We collected hospitalization and weather data for the hot season (the 4 adjacent hottest months for each city) from 1,814 Brazilian cities during 1 January 2000−31 December 2015. We used a time-stratified case-crossover design to quantify the association between heat exposure and hospitalization due to undernutrition. Region-specific odds ratios (ORs) were used to calculate the attributable fractions (AFs). A total of 238,320 hospitalizations for undernutrition were recorded during the 2000−2015 hot seasons. Every 1°C increase in daily mean temperature was associated with a 2.5% (OR 1.025, 95% CI 1.020−1.030, p < 0.001) increase in hospitalizations for undernutrition across lag 0–7 days. The association was greatest for individuals aged ≥80 years (OR 1.046, 95% CI 1.034−1.059, p < 0.001), 0–4 years (OR 1.039, 95% CI 1.024–1.055, p < 0.001), and 5–19 years (OR 1.042, 95% CI 1.015–1.069, p = 0.002). Assuming a causal relationship, we estimate that 15.6% of undernutrition hospitalizations could be attributed to heat exposure during the study period. The AF grew from 14.1% to 17.5% with a 1.1°C increase in mean temperature from 2000 to 2015. The main limitations of this study are misclassification of different types of undernutrition, lack of individual temperature exposure data, and being unable to adjust for relative humidity. Conclusions Our study suggests that global warming might directly increase undernutrition morbidity, by a route other than by threatening food security. This short-term effect is increasingly important with global warming. Global strategies addressing the syndemic of climate change and undernutrition should focus not only on food systems, but also on the prevention of heat exposure.
Circulating plasma exosomes in obstructive sleep apnoea and reverse dipping blood pressure
Authors: Abdelnaby Khalyfa, David Gozal, Wen-Ching Chan, Jorge Andrade, Bharati Prasad
Journal: European Respiratory Journal (2019)

Background Obstructive sleep apnoea (OSA) increases the risk of an abnormal nondipping 24 h blood pressure profile, an independent risk factor for cardiovascular disease (CVD). We examined differential exosomal microRNA (miRNA) expression in untreated OSA patients with normal dipping blood pressure (NDBP) and reverse dipping blood pressure (RDBP), an extreme form of nondipping, to understand the mechanisms underlying nondipping blood pressure in OSA. Methods 46 patients (15 RDBP versus 31 NDBP) matched for OSA severity (respiratory event index 32.6±22.5 versus 32.2±18.1 events·h −1 ; p=0.9), age (54.8±12.9 versus 49±9.9 years; p=0.09) and body mass index (36.2±6.6 versus 34.4±6.8 kg·m −2 ; p=0.4) were included. Plasma exosomes were characterised by flow cytometry and functional in vitro reporter assays were conducted on cultured endothelial cells. Exosome miRNA cargo was profiled with microarrays followed by bioinformatics analyses. Results Exosomes from RDBP patients increased the permeability of endothelial cell tight junctions and adhesion molecule expression. Principal component analyses of miRNA array data showed strict separation and identification of the two groups. A restricted and validated signature of exosomal miRNAs was identified in the RDBP versus NDBP group. Their predicted target genes involved phosphatidylinositol 3-kinase-Akt (p=0.004), Ras (p=3.42E-05), Wnt (p=0.003) and hypoxia inducible factor-1 signalling (p=0.04), inflammatory mediator regulation of transient receptor potential channels (p=0.01), and several cancer-related pathways. Conclusions Patients with RDBP have altered miRNA cargoes in circulating exosomes that invoke in vitro endothelial dysfunction. A selected number of circulating exosomal miRNAs play an important role in abnormal circadian regulation of blood pressure and may provide prognostic biomarkers of CVD risk in OSA.
Cesarean delivery and risk of atopic dermatitis
Authors: Nils Skajaa, Thomas Nørrelykke Nissen, Nina Marie Birk, Dorthe Lisbeth Jeppesen, Lisbeth Marianne Thøstesen, Christine Stabell Benn
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
βKlotho is identified as a target for theranostics in non-small cell lung cancer
Authors: Fan Li, Xiyao Li, Ziming Li, Wenxiang Ji, Shun Lu, Weiliang Xia
Journal: Theranostics (2019)

Non-small cell lung cancer (NSCLC) remains a great challenge, calling for the identification of novel molecular targets with diagnostic/therapeutic value. Here, we sought to characterize the expression of βKlotho and its anti-tumor roles in NSCLC. Methods: The expression of βKlotho was examined in NSCLC cells and tissues by western blot, qRT-PCR and immunohistochemistry staining respectively. Biological roles of βKlotho were revealed by a series of functional in vitro and in vivo studies. Serum βKlotho concentrations of patients were measured using specific ELISA methods. Results: Serum βKlotho concentrations of NSCLC patients were significantly lower than the control group. Moreover, βKlotho expression was negatively associated with lymph node metastasis, overall survival and progression-free survival. Overexpression of βKlotho or exogenous βKlotho administration inhibited the proliferation and migration of NSCLC cells, accompanied by induction of apoptosis, G1 to S phase arrest, and inactivation of ERK1/2, AKT and STAT3 signaling. Furthermore, βKlotho overexpression inhibited NSCLC tumor growth in vivo. Conclusions: βKlotho serves as a novel target for theranostics in NSCLC, which has potential clinical applications in the future.
Strategy to enhance transgene expression in proximity of amyloid plaques in a mouse model of Alzheimer's disease
Authors: Danielle Weber-Adrian, Rikke Hahn Kofoed, Josephine Wing Yee Chan, Joseph Silburt, Zeinab Noroozian, Sebastian Kügler, Kullervo Hynynen, Isabelle Aubert
Journal: Theranostics (2019)

Gene therapy can be designed to efficiently counter pathological features characteristic of neurodegenerative disorders.Here, we took advantage of the glial fibrillary acidic protein (GFAP) promoter to preferentially enhance transgene expression near plaques composed of amyloid-beta peptides (Aβ), a hallmark of Alzheimer's disease (AD), in the TgCRND8 mouse model of amyloidosis.Methods: The delivery of intravenously injected recombinant adeno-associated virus mosaic serotype 1/2 (rAAV1/2) to the cortex and hippocampus of TgCRND8 mice was facilitated using transcranial MRI-guided focused ultrasound in combination with microbubbles (MRIgFUS), which transiently and locally increases the permeability of the blood-brain barrier (BBB).rAAV1/2 expression of the reporter green fluorescent protein (GFP) under a GFAP promoter was compared to GFP expression driven by the constitutive human beta actin (HBA) promoter.Results: MRIgFUS targeting the cortex and hippocampus facilitated the entry of rAAV1/2 and GFP expression under the GFAP promoter was localized to GFAP-positive astrocytes.Adjacent to Aβ plaques where GFAP is upregulated, the volume, surface area, and fluorescence intensity of the transgene GFP were greater in rAAV1/2-GFAP-GFP compared to rAAV1/2-HBA-GFP treated animals.In peripheral organs, GFP expression was particularly strong in the liver, irrespective of the promoter. Conclusion:The GFAP promoter enhanced transgene expression in proximity of Aβ plaques in the brain of TgCRND8 mice, and it also resulted in significant expression in the liver.Future gene therapies for neurological disorders could benefit from using a GFAP promoter to regulate transgene expression in response to disease-induced astrocytic reactivity.
Discrimination, Abuse, Harassment, and Burnout in Surgical Residency Training
Authors: Yue-Yung Hu, Ryan J. Ellis, D. Brock Hewitt, Anthony D. Yang, Elaine Ooi Cheung, Judith T. Moskowitz, John R. Potts, Jo Buyske, David B. Hoyt, Thomas J. Nasca, Karl Y. Bilimoria
Journal: New England Journal of Medicine (2019)

Physicians, particularly trainees and those in surgical subspecialties, are at risk for burnout. Mistreatment (i.e., discrimination, verbal or physical abuse, and sexual harassment) may contribute to burnout and suicidal thoughts.
Changes in clinical trials of cancer drugs in mainland China over the decade 2009–18: a systematic review
Authors: Ning Li, Hui-Yao Huang, Da-Wei Wu, Zhi-Min Yang, Jun Wang, Jian-Sheng Wang, Shu-Hang Wang, Hong Fang, Yue Yu, Ying Bai, Zhao Yan, Ye Cao, Min Jiang, Yan-Fei Liu, Kun-Yan Li, Bing-He Xu, Yan Sun, Jie He
Journal: The Lancet Oncology (2019)
Case 34-2019: A 16-Year-Old Boy with Jaundice
Authors: Brian K. Alverson, Aoife Kilcoyne, Alison M. Friedmann, Aliyah R. Sohani
Journal: New England Journal of Medicine (2019)

A 16-year-old boy was admitted to the hospital in autumn because of malaise, abdominal cramping, and jaundice. Ultrasonography of the abdomen revealed splenomegaly. Atypical lymphocytes were reportedly noted in peripheral blood, and testing for Epstein–Barr virus was negative. Additional diagnostic tests were performed, and a diagnosis was made.
Authors’ reply to Pierce and Bourton, Wight, and Martin
Authors: Maria van Hove, Gillian Leng
Journal: BMJ (2019)

Pierce and Bourton raise an important point on the need to emphasise the carbon impact of drugs in a way that is easily understandable and intuitive.12 Summarised, accessible information for clinicians on the sustainability of treatments would be ideal. Bringing together data on the environmental damage of carbon dioxide, plastics, pollutants, and resource use is essential. This …
Errata
Journal: Journal of Clinical Oncology (2019)

The October 10, 2018, article by ten Broeke et al entitled Cancer Risks for PMS2-Associated Lynch Syndrome (J Clin Oncol 10.1200/JCO.2018.78.4777) was published with an error.  van Hest should have been included in the author list, between Heather Hampel and John Hopper. The following should have appeared in the list of affiliations: Liselotte van Hest, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Under AUTHOR CONTRIBUTIONS,  van Hest should have been included in the section entitled Collection and assembly of data. In the section AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST, the following should have appeared: Liselotte van Hest No relationship to disclose. This has been corrected as of February 18, 2019. The authors apologize for the error.
Bubble-Manipulated Local Drug Release from a Smart Thermosensitive Cerasome for Dual-Mode Imaging Guided Tumor Chemo-Photothermal Therapy
Authors: Suhui Sun, Sujuan Sun, Yan Sun, Ping Wang, Jianlun Zhang, Wenjing Du, Shumin Wang, Xiaolong Liang
Journal: Theranostics (2019)

Thermosensitive liposomes have demonstrated great potential for tumor-specific chemotherapy. Near infrared (NIR) dyes loaded liposomes have also shown improved photothermal effect in cancer theranostics. However, the instability of liposomes often causes premature release of drugs or dyes, impeding their antitumor efficacy. Herein, we fabricated a highly stable thermo-responsive bubble-generating liposomal nanohybrid cerasome with a silicate framework, combined with a NIR dye to achieve NIR light stimulated, tumor-specific, chemo-photothermal synergistic therapy. Methods: In this system, NIR dye of 1,1'-Dioctadecyl-3,3,3',3'- Tetramethylindotricarbocyanine iodide (DiR) with long carbon chains was self-assembled with a cerasome-forming lipid (CFL) to encapsulate ammonium bicarbonate (ABC), which was further used for actively loading doxorubicin (DOX), affording a thermosensitive and photosensitive DOX-DiR@cerasome (ABC). Results: The resulting cerasome could disperse well in different media. Upon NIR light mediated thermal effect, ABC was decomposed to generate CO2 bubbles, resulting in a permeable channel in the cerasome bilayer that significantly enhanced DOX release. After intravenous injection into tumor-bearing mice, DOX-DiR@cerasome (ABC) could be efficiently accumulated at the tumor tissue, as monitored by DiR fluorescence, lasting for more than 5 days. NIR light irradiation was then performed at 36h to locally heat the tumors, resulting in immediate CO2 bubble generation, which could be clearly detected by ultrasound imaging, facilitating the monitoring process of controlled release of the drug. Significant antitumor efficacy could be obtained for the DOX-DiR@cerasome (ABC) + laser group, which was further confirmed by tumor tissue histological analysis.
Erratum: Mina, an I14 repressor, controls T helper type 2 bias (Nature Immunology 10.1038/ni.1747)
Authors: Mariko Okamoto, Melanie Van Stry, Linda Chung, Madoka Koyanagi, Xizhang Sun, Yoshie Suzuki, Osamu Ohara, Hiroshi Kitamura, Atsushi Hijikata, Masato Kubo, Mark Bix
Journal: Nature Immunology (2009)
Epigenetic regulation of macrophages: from homeostasis maintenance to host defense
Authors: Siyuan Chen, Jing Yang, Yuquan Wei, Xiawei Wei
Journal: Cellular and Molecular Immunology (2019)

Abstract Macrophages are crucial members of the innate immune response and important regulators. The differentiation and activation of macrophages require the timely regulation of gene expression, which depends on the interaction of a variety of factors, including transcription factors and epigenetic modifications. Epigenetic changes also give macrophages the ability to switch rapidly between cellular programs, indicating the ability of epigenetic mechanisms to affect phenotype plasticity. In this review, we focus on key epigenetic events associated with macrophage fate, highlighting events related to the maintenance of tissue homeostasis, responses to different stimuli and the formation of innate immune memory. Further understanding of the epigenetic regulation of macrophages will be helpful for maintaining tissue integrity, preventing chronic inflammatory diseases and developing therapies to enhance host defense.
Imaging of T-cells and their responses during anti-cancer immunotherapy
Authors: Massis Krekorian, Gilbert O. Fruhwirth, Mangala Srinivas, Carl G. Figdor, Sandra Heskamp, Timothy H. Witney, Erik H.J.G. Aarntzen
Journal: Theranostics (2019)

Immunotherapy has proven to be an effective approach in a growing number of cancers.Despite durable clinical responses achieved with antibodies targeting immune checkpoint molecules, many patients do not respond.The common denominator for immunotherapies that have successfully been introduced in the clinic is their potential to induce or enhance infiltration of cytotoxic T-cells into the tumour.However, in clinical research the molecules, cells and processes involved in effective responses during immunotherapy remain largely obscure.Therefore, in vivo imaging technologies that interrogate T-cell responses in patients represent a powerful tool to boost further development of immunotherapy.This review comprises a comprehensive analysis of the in vivo imaging technologies that allow the characterisation of T-cell responses induced by anti-cancer immunotherapy, with emphasis on technologies that are clinically available or have high translational potential.Throughout we discuss their respective strengths and weaknesses, providing arguments for selecting the optimal imaging options for future research and patient management.
The Effects of Rare <i>SERPINA1</i> Variants on Lung Function and Emphysema in SPIROMICS
Authors: Victor E. Ortega, Xingnan Li, Wanda K. O’Neal, Lela Lackey, Elizabeth Ampleford, Gregory A. Hawkins, Philip J. Grayeski, Alain Laederach, Igor Barjaktarevic, R. Graham Barr, Christopher Cooper, David Couper, MeiLan K. Han, Richard E. Kanner, Eric C. Kleerup, Fernando J. Martinez, Robert Paine, Stephen P. Peters, Cheryl Pirozzi, Stephen I. Rennard, Prescott G. Woodruff, Eric A. Hoffman, Deborah A. Meyers, Eugene R. Bleecker, Neil E. Alexis, Wayne H. Anderson, Mehrdad Arjomandi, Lori A. Bateman, Surya P. Bhatt, Richard C. Boucher, Russell P. Bowler, Stephanie A. Christenson, Alejandro P. Comellas, Gerard J. Criner, Ronald G. Crystal, Jeffrey L. Curtis, Claire M. Doerschuk, Mark T. Dransfield, Christine M. Freeman, Craig Galban, Nadia N. Hansel, Annette T. Hastie, Yvonne Huang, Robert J. Kaner, Jerry A. Krishnan, Lisa M. LaVange, Stephen C. Lazarus, Wendy C. Moore, Laura Paulin, Nirupama Putcha, Elizabeth C. Oelsner, Sanjeev Raman, Donald P. Tashkin, J. Michael Wells, Robert A. Wise
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin,
Microengineered biosynthesized cellulose as anti-fibrotic in vivo protection for cardiac implantable electronic devices
Authors: Francesco Robotti, Ita Sterner, Simone Bottan, Josep M. Monné Rodríguez, Giovanni Pellegrini, Tanja Schmidt, Volkmar Falk, Dimos Poulikakos, Aldo Ferrari, Christoph Starck
Journal: Biomaterials (2019)

Upon cardiac implantable electronic device (CIED) exchange, upgrade, or revision surgery patients are exposed to a considerable risk of adverse events. The presence of firm fibrotic tissue endangers these procedures. Leads can be damaged in the attempt of freeing them from fibrotic tissue. Hematoma can form as result of capsulectomy, pocket debridement and leads dissection. Due to the increasing number of CIED exchange, upgrade and revision surgeries, the incidence of related complications is expected to rise in the near future.The aim of the study was to evaluate the feasibility, safety, and performance of a rationally micro-engineered non-resorbable biosynthesized cellulose (BC) membrane as conformal wrapping protection around CIED implants. Protective membranes were generated by means of a recently established method to transfer on-demand microscale geometries onto the surface of BC. A chronic minipig animal model was selected to investigate the performance of the BC anti-fibrotic protection, directly measured as reduction of fibrotic tissue formation. Sixteen (n = 16) animals received each one BC coated pacemaker (PMC) and one native pacemaker (BI) at equivalent anatomical sites. BC protective layers were juxtaposed around pacemakers through a fast and well-repeatable procedure. Explants were performed at 3 and 12 months after implantation. Endpoint analysis showed that the BC protective layers were 100% integer, with no sign of chemical or mechanical degradation and appeared as a thin layer of white-tan material, adherent to the surrounding thin fibrous capsule, from which it could be peeled off by gently pulling with forceps. The protective effect of micro-engineered BC yielded an average thickness reduction of 66% of the fibrotic tissue thickness generated around PMC, as compared to that measured around the naked counterpart (i.e. the BI). When protected by in BC, both the generator and the proximal parts of the leads were completely free from fibrotic tissue. The insertion of an anti-adhesive, non-resorbable and well-tolerated BC interface between the implant and the surrounding tissue in the surgical pocket significantly reduced the formation of fibrotic tissue, ensuring an easy access to the device pocket, and thus creating the conditions for simplified CIED revision surgeries.
TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis
Authors: Dehong Yan, Jinghui Wang, Honghong Sun, Ali Zamani, Honglin Zhang, Weihong Chen, Aifa Tang, Qingguo Ruan, Xiaolu Yang, Youhai H. Chen, Xiaochun Wan
Journal: The Journal of Experimental Medicine (2019)

Myeloid-derived suppressor cells (MDSCs) are “polarized” myeloid cells that effectively promote tumorigenesis by inhibiting antitumor immunity. How myeloid cells acquire the protumoral properties during tumorigenesis is poorly understood. We report here that the polarity protein TIPE2 (tumor necrosis factor-α–induced protein 8-like 2) mediates the functional polarization of murine and human MDSCs by specifying their pro- and antitumoral properties. Tumor cells induced the expression of TIPE2 in Gr1+CD11b+ cells through reactive oxygen species (ROS). TIPE2 in turn increased the expression of protumoral mediators such as CCAAT/enhancer-binding protein-β while inhibiting the expression of antitumoral mediators. Consequently, tumor growth in TIPE2-deficient mice was significantly diminished, and TIPE2-deficient MDSCs markedly inhibited tumor growth upon adoptive transfer. Pharmaceutical blockade of ROS inhibited TIPE2 expression in MDSCs and reduced tumor growth in mice. These findings indicate that TIPE2 plays a key role in the functional polarization of MDSCs and represents a new therapeutic target for cancer immunotherapy.
Fluorescent Terpolymers via In Situ Allocation of Aliphatic Fluorophore Monomers: Fe(III) Sensor, High‐Performance Removals, and Bioimaging
Authors: Manas Mahapatra, Arnab Dutta, Joy Sankar Deb Roy, Madhushree Mitra, Sushweta Mahalanobish, MD Hussain Sanfui, Snehasis Banerjee, Pijush Kanti Chattopadhyay, Parames C. Sil, Nayan Ranjan Singha
Journal: Advanced Healthcare Materials (2019)

Abstract Herein, purely aliphatic intrinsically fluorescent terpolymers, i.e., 1 and 2, are synthesized through one‐pot solution polymerization via N–H functionalized and multi C–C/C–N coupled in situ protrusion of fluorescent monomers using two nonemissive monomers. These scalable terpolymers are suitable for highly selective Fe(III) sensing, high‐performance exclusion of Fe(III), logic function and the imaging of normal mammalian Madin–Darby canine kidney and human osteosarcoma cancer cell lines. The structures of terpolymers, in situ attachment of fluorescent monomers, clusteroluminescence, adsorption‐mechanism, and cell‐imaging abilities are understood via unadsorbed and/or adsorbed microstructural analyses using 1 H/ 13 C NMR, Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, UV–vis spectroscopy, atomic absorption spectroscopy, thermogravimetric analysis, high‐resolution transmission electron microscopy, dynamic light scattering, fluorescence imaging, and fluorescence lifetime. The geometries, electronic structures, location of fluorophores, and singlet–singlet absorption and emission of terpolymers are examined using density functional theory (DFT) and time‐dependent DFT. For the precise identification of fluorophores, transition from occupied natural transition orbitals (NTOs) to unoccupied NTOs is computed. For 1/2, limit of detection (LOD) values and adsorption capacities are 6.0 × 10 −7 /8.0 × 10 −7 m and 147.82/120.56 mg g −1 at pH i = 7.0 and 303 K, respectively. The overall properties of 1 are more advantageous compared to 2 in sensing, cell imaging, and adsorptive exclusion of Fe(III).