tbuckley/cabot-search huggingface dataset:
Understanding the microbiome of diabetic foot osteomyelitis: insights from molecular and microscopic approaches
Authors: K. Johani, B.G. Fritz, T. Bjarnsholt, B.A. Lipsky, S.O. Jensen, M. Yang, A. Dean, H. Hu, K. Vickery, M. Malone
Journal: Clinical Microbiology and Infection (2018)

Rigorous visual evidence on whether or not biofilms are involved in diabetic foot osteomyelitis (DFO) is lacking. We employed a suite of molecular and microscopic approaches to investigate the microbiome, and phenotypic state of microorganisms involved in DFO.In 20 consecutive subjects with suspected DFO, we collected intraoperative bone specimens. To explore the microbial diversity present in infected bone we performed next generation DNA sequencing. We used scanning electron microscopy (SEM) and peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with confocal microscopy to visualize and confirm the presence of biofilms.In 19 of 20 (95%) studied patients presenting with DFO, it was associated with an infected diabetic foot ulcer. By DNA sequencing of infected bone, Corynebacterium sp. was the most commonly identified microorganism, followed by Finegoldia sp., Staphylococcus sp., Streptococcus sp., Porphyromonas sp., and Anaerococcus sp. Six of 20 bone samples (30%) contained only one or two pathogens, while the remaining 14 (70%) had polymicrobial communities. Using a combination of SEM and PNA-FISH, we identified microbial aggregates in biofilms in 16 (80%) bone specimens and found that they were typically coccoid or rod-shaped aggregates.The presence of biofilms in DFO may explain why non-surgical treatment of DFO, relying on systemic antibiotic therapy, may not resolve some chronic infections caused by biofilm-producing strains.
Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2)
Authors: Li Zhong, Zongqi Wang, Daxin Wang, Zhe Wang, Yuka A. Martens, Linbei Wu, Ying Xu, Kai Wang, Jianguo Li, Ruizhi Huang, Dan Can, Huaxi Xu, Guojun Bu, Xiao-Fen Chen
Journal: Molecular Neurodegeneration (2018)

TREM2 is an innate immune receptor specifically expressed in microglia. Coding variations in TREM2 have been reported to increase the risk for Alzheimer's disease (AD) and other neurodegenerative diseases. While multiple studies support a role for TREM2 in microglial recruitment to amyloid plaques, the chemoattractant factor modulating TREM2-dependent microglial responses has not been defined.
Abstract 15613: Change in Cardiorespiratory Fitness is Inversely Related to Mortality Among Men and Women: Data From the Henry Ford Exercise Testing (FIT) Project
Authors: Clinton A Brawner, Mouaz H Al-Mallah, Jonathan K Ehrman, Waqas T Qureshi, John R Schairer, Michael J Blaha, Steven J Keteyian
Journal: Circulation (2015)

Background: Cardiorespiratory fitness (CRF) is inversely related to all-cause mortality and cardiovascular-related morbidity and mortality. However, there is limited data describing whether change in CRF is associated with improved outcomes. Hypothesis: Change in CRF between two clinical exercise stress tests is related to risk of all-cause mortality. Methods: In this retrospective, observational study, we identified 14,305 patients (age = 55 ± 11 y; 39% women; 30% non-white) who completed two clinically-indicated exercise tests that were at least 12 mo apart between 1991 and 2009 within the Henry Ford Health System. CRF was quantified in metabolic equivalents of task (METs) estimated from peak treadmill speed and grade. All-cause mortality was identified through April 2013 using the Social Security Death Index. Cox regression analysis was used to evaluate the risk of mortality associated with change in CRF between tests 1 and 2. Change in CRF was analyzed as the change in categorization between Poor Fitness (&lt;7 METs) and Fit (≥ 7 METs) and as an absolute change in peak METs. Based on data at test 1, covariates included age; sex; race; cardiovascular risk factors; medications; and history of coronary artery disease, heart failure, and atrial fibrillation; as well as year of test 1 and time between tests 1 and 2. Results: The mean time between test 1 and 2 was 4.3 ± 2.8 y. During 9.4 ± 3.9 y of follow-up after test 2, there were 1,980 (14%) deaths. Adjusted Cox regression results are shown in the Table. Among all patients, each 1 MET increase in CRF at test 2 was associated with a 5% lower risk of mortality (hazard ratio 95% confidence interval 0.94, 0.97; p &lt; 0.001). Conclusions: Among men and women referred for a clinical exercise test, change in CRF from Poor Fitness to Fit is associated with a 38% lower risk of all-cause mortality relative to patients who remain Poor Fit. These data support the importance of improving CRF and the clinical utility of serial assessments of CRF in risk assessment.
Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis
Authors: Chong Wu, Huiheng Ning, Mingyu Liu, Jie Lin, Shufeng Luo, Wenjie Zhu, Jing Xu, Wen-Chao Wu, Jing Liang, Chun-Kui Shao, Jiaqi Ren, Bin Wei, Jun Cui, Min-Shan Chen, Limin Zheng
Journal: Journal of Clinical Investigation (2018)

Cancer progression is associated with alterations of intra- and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here, we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs). With the distinct capability to produce and respond to granulocyte-macrophage CSF (GM-CSF), these splenic HSPCs were "primed" and committed to generating immunosuppressive myeloid cells. Mechanistically, the CCL2/CCR2 axis–dependent recruitment and the subsequent local education by the splenic stroma were critical for eliciting this splenic HSPC response. Selective abrogation of this splenic EMH was sufficient to synergistically enhance the therapeutic efficacy of immune checkpoint blockade. Clinically, patients with different types of solid tumors exhibited increased splenic HSPC levels associated with poor survival. These findings reveal a unique and important role of splenic hematopoiesis in tumor-associated myelopoiesis.
BCLC subclassification and tumour characteristics to provide prognostication of outcomes in an Asian population of locally advanced hepatocellular carcinoma treated using selective internal radiation therapy with Yttrium-90.
Authors: Eshani Nastassia Mathew, Nivedita Nadkarni, Su-Pin Choo, Han Chong Toh, David Wai-Meng Tai, Brian Goh, Alexander Chung, Chung Yip Chan, David Ng, Anthony Goh, Richard Lo, Nanda Venkatanarasimha, Apoorva Gogna, Chow Wei Too, Julianah Bee Abdul Latiff, Choon Hua Thng, Pierce K. H. Chow
Journal: Journal of Clinical Oncology (2018)

443 Background: Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) is preferentially used in locally advanced hepatocellular carcinoma (HCC) patients in the Barcelona clinic liver cancer (BCLC) B or C cohort. However, the BCLC B cohort has a wide heterogeneity. To address this, Bolondi et al. proposed a BCLC B subclassification system. Additionally, the BCLC C cohort is also diverse in their Child-Pugh (CP) stage and extent of portal vein thrombosis (PVT). The effect of these subclassifications on survival outcomes has not been studied in HCC patients treated using SIRT. Methods: 392 HCC patients treated using SIRT from 1 st January 2008 to 17 th March 2017 were analyzed. These patients were classified according to the proposed subclassification system for the BCLC B cohort, and CP stage for the BCLC C cohort, and their survival outcomes reviewed. Results: 293 patients met the study’s inclusion criteria. For B1/B2/B3/B4/ C CP-A and C CP-B, the median OS was 48.3/28.7/14.4/13.7/12.8 and 6.6 months respectively. Overall comparison between the subgroups for median OS reached statistical significance (p &lt; 0.001). The Cox proportional-hazards regression analysis found that tumour location defined as unilobar or bilobar disease significantly influenced median OS. In the BCLC C cohort, the extent of portal vein invasion significantly influenced median OS (p &lt; 0.001). For the BCLC C CP-A group, median OS for segmental/sectoral branch invasion, right and/or left portal vein invasion and main portal vein trunk invasion was 24.1, 12.8 and 6.5 months respectively. Conclusions: Bolondi et al.’s subclassification system optimizes prognostic prediction by reducing the clinical heterogeneity in BCLC B HCC patients treated using SIRT. However tumour location, unaccounted for in the proposed subclassification, is also an important prognosticator. For the BCLC C cohort CP stage, extent of PVT, and tumour location were important predictors of treatment outcomes.
NCCN Frameworks for Resource Stratification of NCCN Guidelines: Adult Cancer Pain and Palliative Care
Authors: Robert A. Swarm, Maria Dans
Journal: Journal of the National Comprehensive Cancer Network (2018)

The NCCN Framework aims to provide adapted guidelines for low- and middle-resource countries to improve the experience of patients with cancer. In particular, the NCCN Frameworks for Adult Cancer Pain and Palliative Care and were designed to help expand access to pain management and palliative care for patients in low-resource countries. The NCCN Framework is one of several tools that can improve cancer care in the developing world. The NCCN Harmonized Guidelines for Sub-Saharan Africa, a collaborative effort between NCCN, American Cancer Society, Clinton Health Access Initiative, and African Cancer Coalition, was developed to harmonize NCCN recommendations with local guidelines across Africa and to make best use of available services and resources.
Guest Editorial: Breast Milk: An Optimal Food
Authors: Jenny Pronczuk, Gerald Moy, Constanza Vallenas
Journal: Environmental Health Perspectives (2004)

Human breast milk offers the optimal nutrition for all infants and provides immunological, developmental, psychological, economic, and practical advantages when compared to artificial feeding. For proper growth, development, and health, infants should be exclusively breast-fed with no other food or drink—not even water—for their first 6 months of life [World Health Organization (WHO) 2001]; they should then receive nutritionally adequate and safe complementary foods while breast-feeding continues up to 24 months of age or beyond.
Trends in Long-Term Mortality After Congenital Heart Surgery
Authors: Logan G. Spector, Jeremiah S. Menk, Jessica H. Knight, Courtney McCracken, Amanda S. Thomas, Jeffrey M. Vinocur, Matthew E. Oster, James D. St Louis, James H. Moller, Lazaros Kochilas
Journal: Journal of the American College of Cardiology (2018)
Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase
Authors: Dietrich A. Ruess, Guus J. Heynen, Katrin J. Ciecielski, Jiaoyu Ai, Alexandra Berninger, Derya Kabacaoglu, Kivanc Görgülü, Zahra Dantes, Sonja M. Wörmann, Kalliope N. Diakopoulos, Angeliki F. Karpathaki, Marlena Kowalska, Ezgi Kaya-Aksoy, Liang Song, Eveline A. Zeeuw van der Laan, María P. López-Alberca, Marc Nazaré, Maximilian Reichert, Dieter Saur, Mert M. Erkan, Ulrich T. Hopt, Bruno Sainz, Walter Birchmeier, Roland M. Schmid, Marina Lesina, Hana Algül
Journal: Nature Medicine (2018)
Abstract 14109: Basic Life Support With Reperfusion Injury Protection Improves 24 Hour Survival Outcomes in a Porcine Model of Prolonged Cardiac Arrest
Authors: Guillaume Debaty, Keith G Lurie, Anja Metzger, Michael Lick, Jason Bartos, Jennifer N Rees, Scott McKnite, Laura Puertas, Demetris Yannopoulos
Journal: Circulation (2015)

Introduction: Ischemic postconditioning (PC) using 3 intentional short pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. Hypothesis: Basic life support (BLS) with PC will protect against reperfusion injury and enhance 24 hour functional recovery in the absence of epi. Methods: Female pigs (n=46; wt ~ 40 kg) were anesthetized (isoflurane). PC was delivered using 3 cycles alternating between automated CPR for 20 sec and no CPR for 20 sec at the start of each protocol. Protocol A: After 12 minutes of ventricular fibrillation (VF), 28 pigs were randomized in 4 groups: A/ Standard CPR (SCPR), B/ active compression-decompression with an impedance threshold device (ACD-ITD), C/ SCPR+PC (SCPR+PC) and D/ ACD-ITD+PC. Protocol B: After 15 min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD + PC. The BLS duration was 2.75 min in Protocol A and 5 min in Protocol B. Following BLS up to 3 shocks were delivered. Without return of spontaneous circulation (ROSC) CPR was resumed and epi (0.5 mg) and defibrillation delivered. The primary end point was the incidence of major adverse outcomes at 24 h (defined as death or coma, refractory seizures and cardio-respiratory distress leading to euthanasia). Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean ± standard error of mean. Results: Protocol A: ACD-ITD CPR + PC (group D) provided the highest coronary perfusion pressure after 3 min of BLS compared with the 3 other groups (28 ± 6, 35 ± 7, 23 ± 5 and 47 ± 7 for groups A, B, C, D respectively, p= 0.05 by ANOVA). ROSC with BLS was achieved in 0, 3, 0, and 3 pigs in groups A, B, C and D, respectively (p=0.22) with no significant differences in 24-hour survival between groups. Protocol B: Four hours post ROSC, LVEF was significantly higher with ACD-ITD+IPC vs ACD-ITD alone (52.5 ± 3% vs. 37.5 ± 6.6%, p = 0.045). There was a significantly lower incidence of major adverse outcomes 24 hr after ROSC with ACD-ITD+PC compared with ACD-ITD alone (Log-rank comparison, p=0.027). Conclusion: BLS using ACD-ITD + PC mitigates post resuscitation cardiac dysfunction and facilitates neurological recovery after prolonged untreated VF in pigs.
A Call for a Systems-Thinking Approach to Medication Adherence
Authors: Julie C. Lauffenburger, Niteesh K. Choudhry
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Fibrin Stiffness Mediates Dormancy of Tumor-Repopulating Cells via a Cdc42-Driven Tet2 Epigenetic Program
Authors: Yuying Liu, Jiadi Lv, Xiaoyu Liang, Xiaonan Yin, Le Zhang, Degao Chen, Xun Jin, Roland Fiskesund, Ke Tang, Jingwei Ma, Huafeng Zhang, Wenqian Dong, Siqi Mo, Tianzhen Zhang, Feiran Cheng, Yabo Zhou, Jing Xie, Ning Wang, Bo Huang
Journal: Cancer Research (2018)

Abstract Dormancy is recognized as a critical biological event for tumorigenic cells surviving in an extremely harsh environment. Understanding the molecular process of dormancy can unlock novel approaches to tackle cancers. We recently reported that stem-like tumor-repopulating cells (TRC) sense mechanical signals and rapidly proliferate in a 90 Pa soft fibrin matrix. Here, we show that a stiff mechanical environment induces TRC dormancy via an epigenetic program initiated by translocation of Cdc42, a cytosolic regulator of mechanotransduction, into the nucleus, where it promotes transcription of hydroxymethylating enzyme Tet2. Tet2 epigenetically activated cell-cycle–inhibiting genes p21 and p27 to induce dormancy, but also caused downregulation of integrin β3 to maintain dormancy. This stiffness-mediated dormancy was recapitulated in mouse models for both murine and primary human melanoma TRCs. These data identify an epigenetic program directed by mechanics, which drives highly tumorigenic TRCs to enter dormancy in a stiff mechanical environment. Significance: A mechanics-directed epigenetic program enables tumor-repopulating cells to enter dormancy in a stiff mechanical environment. Cancer Res; 78(14); 3926–37. ©2018 AACR.
Neutral pH and low–glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal dialysis
Authors: Betti Schaefer, Maria Bartosova, Stephan Macher-Goeppinger, Peter Sallay, Peter Vörös, Bruno Ranchin, Karel Vondrak, Gema Ariceta, Ariane Zaloszyc, Aysun K. Bayazit, Uwe Querfeld, Rimante Cerkauskiene, Sara Testa, Christina Taylan, Johan VandeWalle, YokChin Yap, Rafael T. Krmar, Rainer Büscher, Anne K. Mühlig, Dorota Drozdz, Salim Caliskan, Felix Lasitschka, Sahar Fathallah-Shaykh, Enrico Verrina, Günter Klaus, Klaus Arbeiter, Raj Bhayadia, Anette Melk, Philipp Romero, Bradley A. Warady, Franz Schaefer, Akos Ujszaszi, Claus Peter Schmitt
Journal: Kidney International (2018)
Convergence of placenta biology and genetic risk for schizophrenia
Authors: Gianluca Ursini, Giovanna Punzi, Qiang Chen, Stefano Marenco, Joshua F. Robinson, Annamaria Porcelli, Emily G. Hamilton, Marina Mitjans, Giancarlo Maddalena, Martin Begemann, Jan Seidel, Hidenaga Yanamori, Andrew E. Jaffe, Karen F. Berman, Michael F. Egan, Richard E. Straub, Carlo Colantuoni, Giuseppe Blasi, Ryota Hashimoto, Dan Rujescu, Hannelore Ehrenreich, Alessandro Bertolino, Daniel R. Weinberger
Journal: Nature Medicine (2018)
Junior doctor wins legal protection for all trainees who report safety concerns
Authors: Deborah Cohen
Journal: BMJ (2018)

Health Education England has conceded that it is an employer of postgraduate medical trainees and that junior doctors who raise concerns in the public interest are protected by statutory law.

The admission came at the start of an employment tribunal on 14 May before any evidence had been heard. The protracted legal battle involves Chris Day, a trainee doctor who raised concerns about understaffing to hospital managers while working in the intensive care unit at Queen Elizabeth Hospital in southeast London.

The acknowledgment of its status as an employer is a U turn for HEE, which had argued since 2015 that junior doctors were not its employees, meaning that they could not take action against it under employment law protections if they believed they had been wronged.

After the latest hearing a spokesperson for HEE told The BMJ , “We have made very clear our position on being considered as a second employer for …
Effect of Vitamin D Supplementation on Recurrent Wheezing in Black Infants Who Were Born Preterm
Authors: Anna Maria Hibbs, Kristie Ross, Leigh Ann Kerns, Carol Wagner, Mamta Fuloria, Sharon Groh-Wargo, Teresa Zimmerman, Nori Minich, Curtis Tatsuoka
Journal: JAMA (2018)

<h3>Importance</h3> Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. <h3>Objective</h3> To assess the effectiveness of 2 vitamin D dosing strategies in preventing recurrent wheezing. <h3>Design, Setting, and Participants</h3> A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks' gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. <h3>Interventions</h3> Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. <h3>Main Outcomes and Measures</h3> Recurrent wheezing by 12 months' adjusted age was the primary outcome. <h3>Results</h3> Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, −10.7% [95% CI, −27.4% to −2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, −1.6% [95% CI, −17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, −3.6% [95% CI, −16.4% to 4.4%]). <h3>Conclusions and Relevance</h3> Among black infants born preterm, sustained supplementation with vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months' adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of vitamin D supplementation on wheezing in children born preterm. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01601847