tbuckley/cabot-search huggingface dataset:
Um ponto de vista multiple para comprender a resurgência e a evolução da sífilis na Europa occidental
Authors: K Fenton
Journal: Eurosurveillance (2004)

Quase oito anos depois du surto de sifilis ocorrido em Bristol, Inglaterra [1], surtos sucesivos afetaram a mayor parte dos paises da Europa occidental [2]. Este numero de Eurosurveillance trata da resurgencia recente e da evolucao da sifilis em sete paises europeus, com o objectivo de fazer uma analise critica de nossa compreensao da epidemiologia de esta doenca, e de propor solucoes para reorientar as accoes no futuro [3-9]. Estes artigos tambem permitem comprender as causas multifactoriais dos surtos de sifilis [10], e as medidas preventivas que podem fazer evoluir esta situacao.
Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices
Authors: Sarah Schillie, Claudia Vellozzi, Arthur Reingold, Aaron Harris, Penina Haber, John W. Ward, Noele P. Nelson
Journal: MMWR Recommendations and Reports (2018)

HEPATITIS B VIRUS (HBV) IS TRANSMITTED VIA BLOOD OR SEXUAL CONTACT. PERSONS WITH CHRONIC HBV INFECTION ARE AT INCREASED RISK FOR CIRRHOSIS AND LIVER CANCER AND REQUIRE MEDICAL CARE. THIS REPORT UPDATES AND SUMMARIZES PREVIOUSLY PUBLISHED RECOMMENDATIONS FROM THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) AND CDC REGARDING THE PREVENTION OF HBV INFECTION IN THE UNITED STATES. ACIP RECOMMENDS TESTING ALL PREGNANT WOMEN FOR HEPATITIS B SURFACE ANTIGEN (HBSAG), AND TESTING HBSAG-POSITIVE PREGNANT WOMEN FOR HEPATITIS B VIRUS DEOXYRIBONUCLEIC ACID (HBV DNA); ADMINISTRATION OF HEPB VACCINE AND HEPATITIS B IMMUNE GLOBULIN (HBIG) FOR INFANTS BORN TO HBV-INFECTED WOMEN WITHIN 12 HOURS OF BIRTH, FOLLOWED BY COMPLETION OF THE VACCINE SERIES AND POSTVACCINATION SEROLOGIC TESTING; UNIVERSAL HEPATITIS B VACCINATION WITHIN 24 HOURS OF BIRTH, FOLLOWED BY COMPLETION OF THE VACCINE SERIES; AND VACCINATION OF CHILDREN AND ADOLESCENTS AGED <19 YEARS WHO HAVE NOT BEEN VACCINATED PREVIOUSLY. ACIP RECOMMENDS VACCINATION OF ADULTS AT RISK FOR HBV INFECTION, INCLUDING UNIVERSAL VACCINATION OF ADULTS IN SETTINGS IN WHICH A HIGH PROPORTION HAVE RISK FACTORS FOR HBV INFECTION AND VACCINATION OF ADULTS REQUESTING PROTECTION FROM HBV WITHOUT ACKNOWLEDGMENT OF A SPECIFIC RISK FACTOR. THESE RECOMMENDATIONS ALSO PROVIDE CDC GUIDANCE FOR POSTEXPOSURE PROPHYLAXIS FOLLOWING OCCUPATIONAL AND OTHER EXPOSURES. THIS REPORT ALSO BRIEFLY SUMMARIZES PREVIOUSLY PUBLISHED AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASEST GUIDELINES FOR MATERNAL ANTIVIRAL THERAPY TO REDUCE PERINATAL HBV TRANSMISSION.
Joint registration and synthesis using a probabilistic model for alignment of MRI and histological sections
Authors: Juan Eugenio Iglesias, Marc Modat, Loïc Peter, Allison Stevens, Roberto Annunziata, Tom Vercauteren, Ed Lein, Bruce Fischl, Sebastien Ourselin
Journal: Medical Image Analysis (2018)

Nonlinear registration of 2D histological sections with corresponding slices of MRI data is a critical step of 3D histology reconstruction. This task is difficult due to the large differences in image contrast and resolution, as well as the complex nonrigid distortions produced when sectioning the sample and mounting it on the glass slide. It has been shown in brain MRI registration that better spatial alignment across modalities can be obtained by synthesizing one modality from the other and then using intra-modality registration metrics, rather than by using mutual information (MI) as metric. However, such an approach typically requires a database of aligned images from the two modalities, which is very difficult to obtain for histology/MRI. Here, we overcome this limitation with a probabilistic method that simultaneously solves for registration and synthesis directly on the target images, without any training data. In our model, the MRI slice is assumed to be a contrast-warped, spatially deformed version of the histological section. We use approximate Bayesian inference to iteratively refine the probabilistic estimate of the synthesis and the registration, while accounting for each other's uncertainty. Moreover, manually placed landmarks can be seamlessly integrated in the framework for increased performance. Experiments on a synthetic dataset show that, compared with MI, the proposed method makes it possible to use a much more flexible deformation model in the registration to improve its accuracy, without compromising robustness. Moreover, our framework also exploits information in manually placed landmarks more efficiently than MI, since landmarks inform both synthesis and registration - as opposed to registration alone. Finally, we show qualitative results on the public Allen atlas, in which the proposed method provides a clear improvement over MI based registration.
Targeting histone deacetylase 4/ubiquitin‐conjugating enzyme 9 impairs DNA repair for radiosensitization of hepatocellular carcinoma cells in mice
Authors: Chiao‐Ling Tsai, Wei‐Lin Liu, Feng‐Ming Hsu, Po‐Sheng Yang, Ruoh‐Fang Yen, Kai‐Yuan Tzen, Ann‐Lii Cheng, Pei‐Jer Chen, Jason Chia‐Hsien Cheng
Journal: Hepatology (2017)

Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach is to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or short hairpin RNA to knock down expression of HDAC4 and then irradiated (2.5‐10.0 Gy). We evaluated cell survival by a clonogenic assay; apoptosis by Annexin V immunofluorescence; γH2AX, Rad51, and HDAC4 by immunofluorescence staining; HDAC4, Rad51, and ubiquitin‐conjugating enzyme 9 (Ubc9) in HCC cell nuclei by cell fractionation and confocal microscopy; physical interaction between HDAC4/Rad51/Ubc9 by immunoprecipitation; and the downstream targets of HDAC4 knockdown by immunoblotting. Both HDAC4 knockdown and HDAC inhibitor enhanced radiation‐induced cell death and reduced homologous recombination repair of DNA double‐strand breaks and protein kinase B activation, leading to increased apoptosis. HDAC4 knockdown with or without an HDAC inhibitor significantly delayed tumor growth in a radiation‐treated xenograft model. Radiation stimulated nuclear translocation of Rad51 in an HDAC4‐dependent manner and the binding of Ubc9 directly to HDAC4, which led to Ubc9 acetylation. Moreover, these effects were accompanied by HDAC4/Ubc9/Rad51 complex dissociation through inhibiting nuclear translocation. Conclusion: HDAC4 signaling blockade enhances radiation‐induced lethality in HCC cells and xenografts. These findings raise the possibility that HDAC4/Ubc9/Rad51 complex in DNA repair may be a target for radiosensitization of HCC. (H epatology 2018;67:586‐599).
Designing 3D Biological Surfaces via the Breath‐Figure Method
Authors: Shuangshuang Chen, Su Gao, Jiange Jing, Qinghua Lu
Journal: Advanced Healthcare Materials (2018)

Abstract The fabrication of biointerfaces that mimic cellular physiological environments is critical to understanding cell behaviors in vitro and for the design of tissue engineering. Breath figure is a self‐assemble method that uses water droplets condensed from moisture as template and ends up with a highly ordered hexagonal pore array; this approach is used to fabricate various biological substrates. This progress report provides an overview of strategies to achieve topographical modifications and chemical‐patterned arrays, such as modulation of the pore size, shape and selective decoration of the honeycomb holes. Using recent results in the biological fields, potential future applications and developments of honeycomb structures are commented upon.
Review: Newer second-line drugs for diabetes are not more cost-effective than sulfonylureas
Authors: Natalia Genere, Victor M. Montori
Journal: Annals of Internal Medicine (2018)

ACP Journal Club16 January 2018Review: Newer second-line drugs for diabetes are not more cost-effective than sulfonylureasNatalia Genere, MD, Victor M. Montori, MD, MScNatalia Genere, MDMayo Clinic, Rochester, Minnesota, USA (N.G., V.M.M.), Victor M. Montori, MD, MScMayo Clinic, Rochester, Minnesota, USA (N.G., V.M.M.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-168-2-008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationCADTH Therapeutic Reviews. New drugs for type 2 diabetes: second-line therapy–science report. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health; Sep 2017.Clinical Impact RatingsGIM/FP/GP: Cardiology: Endocrinology: References1 Rodríguez-Gutiérrez R, Montori VM. Glycemic control for patients with type 2 diabetes mellitus: our evolving faith in the face of evidence. Circ Cardiovasc Qual Outcomes. 2016;9:504-12. [PMID: 27553599] Google Scholar2 Huang ES, Laiteerapong N, Liu JY, et al. Rates of complications and mortality in older patients with diabetes mellitus: the diabetes and aging study. JAMA Intern Med. 2014;174:251-8. [PMID: 24322595] Google Scholar Author, Article, and Disclosure InformationAffiliations: Mayo Clinic, Rochester, Minnesota, USA (N.G., V.M.M.)This article was published at Annals.org on 2 January 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHypoglycemia in type 2 diabetes mellitus patients — cerebral, cognitive, psychosocial and clinical aspectsThe optimization of ultrasonic-microwave assisted synergistic extraction of Lotus plumule extract rich in flavonoids and its hypoglycemic activityCurrent data on the effectiveness of gliclazide and molecular mechanisms of action of the drugrs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up StudyManagement of Type 2 Diabetes in Developing Countries: Balancing Optimal Glycaemic Control and Outcomes with Affordability and Accessibility to TreatmentPhysicochemical properties of polysaccharides separated from Camellia oleifera Abel seed cake and its hypoglycemic activity on streptozotocin-induced diabetic mice 16 January 2018Volume 168, Issue 2Page: JC8KeywordsDrugsHypoglycemiaHypoglycemicsInsulinInsulin-like growth factorsMortalityNetwork analysisSafetySafety studiesType 2 diabetes ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia
Authors: Jinghua Wang, Siyu Chen, Wei Xiao, Wende Li, Liang Wang, Shuo Yang, Weida Wang, Liping Xu, Shuangye Liao, Wenjian Liu, Yang Wang, Nawei Liu, Jianeng Zhang, Xiaojun Xia, Tiebang Kang, Gong Chen, Xiuyu Cai, Han Yang, Xing Zhang, Yue Lu, Penghui Zhou
Journal: Journal of Hematology & Oncology (2018)

Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment. We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific single-chain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-ζ signaling domain. We further investigate the function of CLL-1 CAR-T cells. The CLL-1 CAR-T cells specifically lysed CLL-1+ cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1+ myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression. CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML.
Comparison of sensitisation to prevalent allergens in children vesus adolescents in the same geographical area
Authors: Jose Alessandro Bastidas-Parlanti, Damian López-Sánchez, Maria Luisa Somoza, Elisa Haroun, Natalia Blanca-López, Laura Victorio-Puche, María Vazquez de la Torre, Maria Isabel Garcimartin, Miguel Blanca, María Gabriela Canto
Journal: Journal of Allergy and Clinical Immunology (2018)
Non-genetic engineering of cytotoxic T cells to target IL-4 receptor enhances tumor homing and therapeutic efficacy against melanoma
Authors: Gowri Rangaswamy Gunassekaran, Chae-Moon Hong, Sri Murugan Poongkavithai Vadevoo, Lianhua Chi, Padmanaban Guruprasath, Byung-Cheol Ahn, Ha-Jeong Kim, Tae Heung Kang, Byungheon Lee
Journal: Biomaterials (2018)
Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial
Authors: Kim N Chi, Andrew Protheroe, Alfredo Rodríguez-Antolín, Gaetano Facchini, Henrik Suttman, Nobuaki Matsubara, Zhangqun Ye, Bhumsuk Keam, Ronaldo Damião, Tracy Li, Kelly McQuarrie, Bin Jia, Peter De Porre, Jason Martin, Mary B Todd, Karim Fizazi
Journal: The Lancet Oncology (2018)
Abstract 10200: Translational Research of Novel Angiogenic Peptide for Wound Healing Drug; From Discovery to Clinical Trial
Authors: Hironori Nakagami, Ryuichi Morishita
Journal: Circulation (2015)

We developed a novel cationic peptide, AG30/5C, with angiogenic properties. Since it has both angiogenic and antimicrobial actions, it might be a candidate peptide for wound healing drug. We conducted a physician-initiated clinical trial of AG30/5C for severe skin ulcer in patients as an open label study. The primary outcome is safety because it is first in human trial on early stage. AG30/5C was administered with patients with skin ulcer twice per day for two weeks, and ulcer size and Methicillin-Resistant Staphylococcus Aureus amount was quantified as a secondary outcome. Two patients was registered until now and the skin ulcer of first patient was completely cured after AG30/5C treatment. The Methicillin-Resistant Staphylococcus Aureus amount of both patients was decreased during the AG30/5C treatment. This result suggests the potential of AG30/5C as a wound healing drug, however, improvement of stability and cost efficiency are required toward drug development. Thus, we addressed to the metabolites of AG30/5C which can provide a further optimized compound, SR-0379. SR-0379 also enhanced proliferation, tube formation, migration and contraction on human dermal fibroblast cells via the PI3K-Akt-mTOR pathway through integrin-mediated interactions. We evaluated the effect of SR-0379 on two different would healing model in rats, the full-thickness defects in diabetic condition and an acutely infected wound with the full-thickness defects and inoculation with S aureus. Treatment of SR-0379 significantly accelerated the wound healing compared to that of FGF2. The beneficial effects of SR-0379 on wound healing would be explained by enhanced angiogenesis, granulation tissue formation, proliferation and antimicrobial activity. These results clearly demonstrated that SR-0379 may have a potential for drug development in wound repairing, in especially critical colonization condition. Based on these results, we now conducted the physician-initiated clinical trial for severe skin ulcer in patients as a double blind study.
Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea
Authors: Scott A. Sands, Bradley A. Edwards, Philip I. Terrill, Luigi Taranto-Montemurro, Ali Azarbarzin, Melania Marques, Lauren B. Hess, David P. White, Andrew Wellman
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patient's own phenotypic causes ("traits") if a clinically applicable approach were available.
The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms
Authors: Anna de Breij, Martijn Riool, Robert A. Cordfunke, Nermina Malanovic, Leonie de Boer, Roman I. Koning, Elisabeth Ravensbergen, Marnix Franken, Tobias van der Heijde, Bouke K. Boekema, Paulus H. S. Kwakman, Niels Kamp, Abdelouahab El Ghalbzouri, Karl Lohner, Sebastian A. J. Zaat, Jan W. Drijfhout, Peter H. Nibbering
Journal: Science Translational Medicine (2018)

Infections refractory to conventional antibiotics may be targeted by the antimicrobial peptide SAAP-148.
NACSELD acute‐on‐chronic liver failure (NACSELD‐ACLF) score predicts 30‐day survival in hospitalized patients with cirrhosis
Authors: Jacqueline G. O'Leary, K. Rajender Reddy, Guadalupe Garcia‐Tsao, Scott W. Biggins, Florence Wong, Michael B. Fallon, Ram M. Subramanian, Patrick S. Kamath, Paul Thuluvath, Hugo E. Vargas, Benedict Maliakkal, Puneeta Tandon, Jennifer Lai, Leroy R. Thacker, Jasmohan S. Bajaj
Journal: Hepatology (2018)

The North American Consortium for the Study of End‐Stage Liver Disease's definition of acute‐on‐chronic liver failure (NACSELD‐ACLF) as two or more extrahepatic organ failures has been proposed as a simple bedside tool to assess the risk of mortality in hospitalized patients with cirrhosis. We validated the NACSELD‐ACLF's ability to predict 30‐day survival (defined as in‐hospital death or hospice discharge) in a separate multicenter prospectively enrolled cohort of both infected and uninfected hospitalized patients with cirrhosis. We used the NACSELD database of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 2,675). The cohort was randomly split 60%/40% into training (n = 1,605) and testing (n = 1,070) groups. Organ failures assessed were (1) shock, (2) hepatic encephalopathy (grade III/IV), (3) renal (need for dialysis), and (4) respiratory (mechanical ventilation). Patients were most commonly Caucasian (79%) men (62%) with a mean age of 57 years and a diagnosis of alcohol‐induced cirrhosis (45%), and 1,079 patients had an infection during hospitalization. The mean Model for End‐Stage Liver Disease score was 19, and the median Child score was 10. No demographic differences were present between the two split groups. Multivariable modeling revealed that the NACSELD‐ACLF score, as determined by number of organ failures, was the strongest predictor of decreased survival after controlling for admission age, white blood cell count, serum albumin, Model for End‐Stage Liver Disease score, and presence of infection. The c‐statistics were 0.8073 for the training set and 0.8532 for the validation set. Conclusion: Although infection status remains an important predictor of death, NACSELD‐ACLF was independently validated in a separate large multinational prospective cohort as a simple, reliable bedside tool to predict 30‐day survival in both infected and uninfected patients hospitalized with a diagnosis of cirrhosis. (H epatology 2018;67:2367‐2374).
ENHANCEMENT OF SORAFENIB SENSITIVITY VIA AKT DOWN-REGULATION BY PROTEIN DISULFIDE ISOMERASE INHIBITION OR PTEN ACTIVATION
Authors: Su Jong Yu, Jung-Hwan Yoon, Jeong-Hoon Lee, Eun Sun Jang, Eun Ju Cho, Hyo-Suk Lee, Yoon Jun Kim, Min-Sun Kwak
Journal: Hepatology (2010)
Immunoprofile of α‐Gal‐ and B‐antigen‐specific responses differentiates red meat‐allergic patients from healthy individuals
Authors: D. Apostolovic, R. Rodrigues, P. Thomas, M. Starkhammar, C. Hamsten, M. van Hage
Journal: Allergy (2018)

Abstract Background The galactose‐α‐1,3‐galactose (α‐Gal) epitope is involved in red meat allergy. As α‐Gal is structurally similar to the blood group B‐antigen, we explored the relationship between the immune responses to α‐Gal‐ and the B‐antigen in red meat‐allergic patients compared to healthy A/O or B blood donors. Methods Sera from 51 red meat‐allergic patients IgE‐positive to α‐Gal and 102 healthy blood donors (51 blood group A/O; 51 blood group B) were included. α‐Gal‐ and B‐antigen‐specific IgE (Immuno CAP ) and IgG/IgG 1‐4 ( ELISA ) responses were determined. Basophil activation tests were performed. Results Fifteen healthy donors were IgE positive to α‐Gal, of which 3 had blood group B. The allergic patients had significantly higher α‐Gal IgE levels compared to the healthy donors. The majority of the allergic patients, but none of the healthy donors, had IgE against the B‐antigen. Inhibition studies revealed cross‐reactivity between α‐Gal and the B‐antigen. The biological activity of the B‐antigen was confirmed by basophil activation tests. Anti‐α‐Gal IgG 1 and IgG 4 levels were significantly higher in the patients compared to the healthy donors. Moreover, the IgG response to the B‐antigen was comparable between the allergic patients and healthy A/O donors. Conclusion Red meat‐allergic patients showed significantly higher α‐Gal IgE, IgG 1 , and IgG 4 levels, reflecting a Th2 response, compared to healthy blood donors. Blood group B donors had significantly reduced antibody responses to α‐Gal, due to similarities with the B‐antigen, resulting in a lower risk of sensitization to α‐Gal and development of red meat allergy.
High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious
Authors: Caio C. A. Morais, Yukiko Koyama, Takeshi Yoshida, Glauco M. Plens, Susimeire Gomes, Cristhiano A. S. Lima, Ozires P. S. Ramos, Sérgio M. Pereira, Naomasa Kawaguchi, Hirofumi Yamamoto, Akinori Uchiyama, João B. Borges, Marcos F. Vidal Melo, Mauro R. Tucci, Marcelo B. P. Amato, Brian P. Kavanagh, Eduardo L. V. Costa, Yuji Fujino
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious.To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP).Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS.Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients).Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.