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| 1 | Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”显示文摘Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure. | Elysia A. Masters Ryan P. Trombetta Karen L. de Mesy Bentley Brendan F Boyce Ann Lindley Gill Steven R. Gill Kohei Nishitani Masahiro Ishikawa Yugo Morita Hiromu Ito Sheila N. Bello-Irizarry Mark Ninomiya James D. Brodell Jr. Charles C. Lee Stephanie P. Hao Irvin Oh Chao Xie Hani A. Awad John L. Daiss John R. Owen Stephen L. Kates Edward M. Schwarz Gowrishankar Muthukrishnan | 2019 | Bone Research2019，7，3： | 19 |
| 2 | Risk factors for post-ERCP pancreatitis: A prospective, multicenter study显示文摘 | Martin L. Freeman James A. DiSario Douglas B. Nelson M.Brian Fennerty John G. Lee David J. Bjorkman Carol S. Overby Johannes Aas Michael E. Ryan Gary S. Bochna Michael J. Shaw Harry W. Snady Robert V. Erickson Joseph P. Moore Joseph P. Roel | 2001 | Gastrointestinal Endoscopy2001，，4： | 5 |
| 3 | Malaria: Global progress 2000-2015 and future challenges显示文摘Background:2015 was the target year for malaria goals set by the World Health Assembly and other international institutions to reduce malaria incidence and mortality.A review of progress indicates that malaria programme financing and coverage have been transformed since the beginning of the millennium,and have contributed to substantial reductions in the burden of disease.Findings:Investments in malaria programmes increased by more than 2.5 times between 2005 and 2014 from US$960 million to US$2.5 billion,allowing an expansion in malaria prevention,diagnostic testing and treatment programmes.In 2015 more than half of the population of sub-Saharan Africa slept under insecticide-treated mosquito nets,compared to just 2%in 2000.Increased availability of rapid diagnostic tests and antimalarial medicines has allowed many more people to access timely and appropriate treatment.Malaria incidence rates have decreased by 37%globally and mortality rates by 60%since 2000.It is estimated that 70%of the reductions in numbers of cases in sub-Saharan Africa can be attributed to malaria interventions.Conclusions:Reductions in malaria incidence and mortality rates have been made in every WHO region and almost every country.However,decreases in malaria case incidence and mortality rates were slowest in countries that had the largest numbers of malaria cases and deaths in 2000;reductions in incidence need to be greatly accelerated in these countries to achieve future malaria targets.Progress is made challenging because malaria is concentrated in countries and areas with the least resourced health systems and the least ability to pay for system improvements.Malaria interventions are nevertheless highly cost-effective and have not only led to significant reductions in the incidence of the disease but are estimated to have saved about US$900 million in malaria case management costs to public providers in sub-Saharan Africa between 2000 and 2014.Investments in malaria programmes can not only reduce malaria morbidity and mortality,thereby contributing to the health targets of the Sustainable Development Goals,but they can also transform the well-being and livelihood of some of the poorest communities across the globe. | Richard E.Cibulskis Pedro Alonso John Aponte Maru Aregawi Amy Barrette Laurent Bergeron Cristin A.Fergus Tessa Knox Michael Lynch Edith Patouillard Silvia Schwarte Saira Stewart Ryan Williams | 2016 | Infectious Diseases of Poverty2016，5，1： | 4 |
| 4 | Chinese Renminbi Arrival in the "Tripolar" Global Monetary Regime显示文摘 | John Ryan | 2015 | China & World Economy2015，23，6： | 4 |
| 5 | Macrophages are the primary effector cells in IL-7-induced arthritis显示文摘Synovial macrophages are crucial in the development of joint inflammation and bone damage;however, the pathways that controlmacrophage remodeling in inflammatory M1 cells or bone-eroding osteoclasts are not fully understood. We determined thatelevated IL-7R/CD127 expression is the hallmark of rheumatoid arthritis (RA) M1 macrophages and that these cells are highlyresponsive to interleukin-7 (IL-7)-driven osteoclastogenesis. We established that lipopolysaccharide (LPS), interferon-γ (IFNγ), andtumor necrosis factor-α (TNFα), the classic M1 macrophage mediators, enhance IL-7R expression in RA and murine macrophages.The local expression of IL-7 provokes arthritis, predominantly through escalating the number of F480^(+)iNOS^(+) cells rather than CD3^(+)T cells. Ectopic LPS injection stabilizes IL-7-induced arthritis by increasing myeloid IL-7R expression, in part via IFNγ induction.Hence, in RAG−/− mice, IL-7-mediated arthritis is suppressed because of the reduction in myeloid IL-7R expression due to the lackof IFNγ. Moreover, the amelioration of IL-7-induced arthritis by anti-TNF therapy is due to a decrease in the number of cells in theunique F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) subset, with no impact on the F480^(+)Arginase^(+) cell or CD3^(+) T cell frequency. Consistent with thepreclinical findings, the findings of a phase 4 study performed with RA patients following 6 months of anti-TNF therapy revealedthat IL-7R expression was reduced without affecting the levels of IL-7. This study shifts the paradigm by discovering that IL-7-induced arthritis is dependent on F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) cell function, which activates TH-1 cells to amplify myeloid IL-7Rexpression and disease severity. | Seung-jae Kim Huan J.Chang Michael VVolin Sadiq Umar Katrien Van Raemdonck Aimee Chevalier Karol Palasiewicz John W.Christman Suncica Volkov Shiva Arami Mehrdad Maz Anjali Mehta Ryan K.Zomorrodi David A.Fox Nadera Sweiss Shiva Shahrara | 2020 | Cellular & Molecular Immunology2020，17，7： | 4 |
| 6 | Autonomic responses to blast overpressure can be elicited by exclusively exposing the ear in rats显示文摘Blast overpressure has become an increasing cause of brain injuries in both military and civilian populations. Though blast's direct effects on the cochlea and vestibular organs are active areas of study, little attention has been given to the ear's contribution to the overall spectrum of blast injury. Acute autonomic responses to blast exposure, including bradycardia and hypotension, can cause hypoxia and contribute to blast-induced neurotrauma. Existing literature suggests that these autonomic responses are elicited through blast impacting the thorax and lungs. We hypothesize that the unprotected ear also provides a vulnerable locus for blast to cause autonomic responses. We designed a blast generator that delivers controlled overpressure waves into the ear canal without impacting surrounding tissues in order to study the ear's specific contribution to blast injury. Anesthetized adult rats' left ears were exposed to a single blast wave ranging from 0 to 110 PSI(0-758 kPa). Blast exposed rats exhibited decreased heart rates and blood pressures with increased blast intensity, similar to results gathered using shock tubes and whole-body exposure in the literature. While rats exposed to blasts below 50 PSI(345 kPa) exhibited increased respiratory rate with increased blast intensity, some rats exposed to blasts higher than 50 PSI(345 kPa) stopped breathing immediately and ultimately died. These autonomic responses were significantly reduced in vagally denervated rats, again similar to whole-body exposure literature. These results support the hypothesis that the unprotected ear contributes to the autonomic responses to blast. | David S.Sandlin Yue Yu Jun Huang Chunming Zhang Alberto A.Arteaga John K.Lippincott Erin O.H.Peeden Ryan R.Guyton Lan Chen Laura L.S.Beneke Jerome C.Allison Hong Zhu Wu Zhou | 2018 | Journal of Otology2018，13，2： | 2 |
| 7 | Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart: A Statement for Healthcare Professionals From the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association显示文摘 | Manuel D. Cerqueira Neil J. Weissman Vasken Dilsizian Alice K. Jacobs Sanjiv Kaul Warren K. Laskey Dudley J. Pennell John A. Rumberger Thomas Ryan Mario S. Verani | 2002 | Circulation: Journal of the American Heart Association2002，，： | 2 |
| 8 | Simpli?ed point-of-care ultrasound protocol to con?rm central venous catheter placement:A prospective study显示文摘BACKGROUND: The current standard for con? rmation of correct supra-diaphragmatic central venous catheter(CVC) placement is with plain ? lm chest radiography(CXR). We hypothesized that a simple point-of-care ultrasound(POCUS) protocol could effectively con? rm placement and reduce time to con? rmation.METHODS: We prospectively enrolled a convenience sample of patients in the emergency department and intensive care unit who required CVC placement. Correct positioning was considered if turbulent flow was visualized in the right atrium on sub-xiphoid, parasternal or apical cardiac ultrasound after injecting 5 cc of sterile, non-agitated, normal saline through the CVC.RESULTS: Seventy-eight patients were enrolled. POCUS had a sensitivity of 86.8%(95%CI 77.1%–93.5%) and speci? city of 100%(95%CI 15.8%–100.0%) for identifying correct central venous catheter placement. Median POCUS and CXR completion were 16 minutes(IQR 10–29) and 32 minutes(IQR 19–45), respectively.CONCLUSION: Ultrasound may be an effective tool to confirm central venous catheter placement in instances where there is a delay in obtaining a con? rmatory CXR. | Scan P.Wilson Samer Assaf Shadi Lahham Mohammad Subeh Alan Chiem Craig Anderson Samantha Shwe Ryan Nguyen John C.Fox | 2017 | World Journal of Emergency Medicine2017，8，1： | 2 |
| 9 | A Cost-Utility Analysis of Ablative Therapy for Barrett’s Esophagus显示文摘 | John M. Inadomi Ma Somsouk Ryan D. Madanick Jennifer P. Thomas Nicholas J. Shaheen | 2009 | Gastroenterology2009，，7： | 2 |
| 10 | The Relationship Between Institutional Expenditures and Degree Attainment at Baccalaureate Colleges显示文摘 | John F. Ryan | 2004 | Research in Higher Education2004，，2： | 2 |
| 11 | Percutaneous transluminal angioplasty balloons for endoscopic ultrasound-guided pancreatic duct interventions显示文摘BACKGROUND Endoscopic ultrasound(EUS)-guided main pancreatic duct(PD)access may be used when conventional endoscopic retrograde cholangiopancreatography(ERCP)techniques fail.The use of a percutaneous transluminal angioplasty balloon(PTAB),originally developed for vascular interventions,can be used to facilitate transmural(e.g.,transgastric)PD access and to dilate high-grade pancreatic strictures.AIM To describe the technique,efficacy,and safety of PTABs for EUS-guided PD interventions.METHODS Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database.PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire.The primary outcome was technical success.Secondary outcomes included incidence of adverse events(AEs)and need for early reintervention.RESULTS A total of 23 patients were identified(48%female,mean age 55.8 years).Chronic pancreatitis was the underlying etiology in 13(56.5%)patients,surgically altered anatomy(SAA)with stricture in 7(30.4%),and SAA with post-operative leak in 3(13.0%).Technical success was achieved in 20(87%)cases.Overall AE rate was 26%(n=6).All AEs were mild and included 1 pancreatic duct leak,2 cases of post-procedure pancreatitis,and 3 admissions for post-procedural pain.No patients required early re-intervention.CONCLUSION EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails. | Jad P AbiMansour Barham K Abu Dayyeh Michael J Levy Andrew C Storm John A Martin Bret T Petersen Ryan J Law Mark D Topazian Vinay Chandrasekhara | 2022 | World Journal of Gastrointestinal Endoscopy2022，14，8： | 2 |
| 12 | A Cost-Utility Analysis of Ablative Therapy for Barrett’s Esophagus显示文摘 | John M. Inadomi Ma Somsouk Ryan D. Madanick Jennifer P. Thomas Nicholas J. Shaheen | 2009 | Gastroenterology2009，，： | 2 |
| 13 | Long-term outcomes after fractional flow reserve-guided percutaneous coronary intervention in patients with severe coronary stenosis显示文摘Objective To explore the safety and efficacy of FFR-guided percutaneous coronary intervention (PCI) in vessels with severe diameter stenosis. Methods & Results Of 1090 patients undergoing fractional flow reserve (FFR) assessment from 2002 to 2009,we identified 167 patients in whom FFR was measured in at least one 70%–89% stenotic lesion. These patients were subdivided into an FFR-defer group (n = 49) if PCI was deferred (FFR > 0.80),and an FFR-perform group (n = 118) if PCI was performed (FFR ≤ 0.80). Comparatively,an additional 1176 patients undergoing PCI in at least one lesion with 70%–89% stenosis but without measurement of FFR served as a control (angiography- guided) group. Clinical outcomes were compared during a median follow-up of 49.0 months. The 5-year Kaplan-Meier estimated revascularization rates were 16% in the FFR-defer group and 33% in the FFR-perform group (P = 0.046). The incidence of major adverse cardiac events were comparable in these two groups (HR = 0.82,95% CI: 0.37–1.82,P = 0.63). The number of stents placed was significantly lower in the FFR-guided group (0.9 ± 0.8 vs. 1.4 ± 0.8,P < 0.001). Conclusions Functional revascularization for lesions with visually severe stenosis is clinically safe and associated with fewer stents use. This study suggests that extending the use of FFR to more severe coronary lesions may be reasonable. | Ying-Hua ZHANG Jing LI Andreas J. Flammer Yoshiki Matsuo Moo-Sik Lee Ryan J. Lennon Malcolm R. Bell David R. Holmes John F. Bresnahan Charanjit S. Rihal Lilach O. Lerman Amir Lerman | 2019 | Journal of Geriatric Cardiology2019，16，4： | 2 |
| 14 | Evidence for colorectal sarcomatoid carcinoma arising from tubulovillous adenoma显示文摘Sarcomatoid carcinomas of the colorectum are rare tu- mors that display both malignant epithelial and stromal components. Clinically, they are aggressive tumors with early metastasis. Due to their infrequent occurrence, the pathogenesis is poorly understood. We report a case of a 52-year-old woman who presented with a rectal mass and intermittent hematochezia. Superficial biopsies during colonoscopy revealed a tubulovillous adenoma with high-grade dysplasia. Endoscopic ultra- sonography confirmed an invasive nature of the mass, and deeper biopsies revealed the presence of neoplasm with mixed histological components. The surgically- excised specimen demonstrated the presence of poorly differentiated spindle cells underneath the tubulovillous adenoma and an intermediate stage of invasive adeno- carcinoma. Based on the histological appearance and immunohistochemical studies, a diagnosis of sarcoma- toid carcinoma was made. Only nine cases of sarcoma- toid carcinomas of the colorectum have been reported to date. As a result, the terminology and pathogenesis of sarcomatoid carcinoma remain speculative. To the best of our knowledge, this is the first report of co- existence of sarcomatoid carcinoma and invasive ad- enocarcinoma with tubulovillous adenoma; all stages represented within the same tumor. This observation supports the 'monoclonal theory' of pathogenesis with an adenoma-sarcoma progression with or without an intermediate stage of carcinoma. | Jeffrey K Lee Pradipta Ghosh Valerie McWhorter Misty Payne Ryan Olson Mary L Krinsky Sonia Ramamoorthy John M Carethers | 2008 | World Journal of Gastroenterology2008，14，27： | 2 |
| 15 | Blockade of PD1 and TIM3 Restores Innate and Adaptive Immunity in Patients with Acute Alcoholic Hepatitis显示文摘 | Lee J.L. Markwick Antonio Riva Jennifer M. Ryan Helen Cooksley Elena Palma Tom H. Tranah Godhev K. Manakkat Vijay Nikhil Vergis Mark Thursz Alex Evans Gavin Wright Sarah Tarff John O’Grady Roger Williams Debbie L. Shawcross Shilpa Chokshi | 2014 | Gastroenterology2014，，： | 2 |
| 16 | Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses显示文摘His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4+ and CD8+ T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome. | Ryan AAdams Cátia Fernandes-Cerqueira Antonella Notarnicola Elisabeth Mertsching Zhiwen Xu Wing-Sze Lo Kathleen Ogilvie Kyle PChiang Jeanette Ampudia Sanna Rosengren Andrea Cubitt David JKing John DMendlein Xiang-Lei Yang Leslie ANangle Ingrid ELundberg Per-Johan Jakobsson Paul Schimmel | 2021 | Cellular & Molecular Immunology2021，18，6： | 2 |
| 17 | Risk factors for post-ERCP pancreatitis: A prospective, multicenter study显示文摘 | Martin L. Freeman James A. DiSario Douglas B. Nelson M.Brian Fennerty John G. Lee David J. Bjorkman Carol S. Overby Johannes Aas Michael E. Ryan Gary S. Bochna Michael J. Shaw Harry W. Snady Robert V. Erickson Joseph P. Moore Joseph P. Roel | 2001 | Gastrointestinal Endoscopy2001，，4： | 2 |
| 18 | Molecular Genetic Evidence for a Common Clonal Origin of Urinary Bladder Small Cell Carcinoma and Coexisting Urothelial Carcinoma显示文摘 | Liang Cheng Timothy D. Jones Ryan P. McCarthy John N. Eble Mingsheng Wang Gregory T. MacLennan Antonio Lopez-Beltran Ximing J. Yang Michael O. Koch Shaobo Zhang Chong-Xian Pan Lee Ann Baldridge | 2005 | The American Journal of Pathology2005，，5： | 2 |
| 19 | Work Values and Organizational Citizenship Behaviors: Values That Work for Employees and Organizations显示文摘 | John J. Ryan | 2002 | Journal of Business and Psychology2002，，1： | 1 |
| 20 | THE IL-4 RECEPTOR: Signaling Mechanisms and Biologic Functions显示文摘 | Keats Nelms Achsah D. Keegan José Zamorano John J. Ryan William E. Paul | 1999 | Annual Review of Immunology1999，，： | 1 |
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