bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the roles of substrate‐binding surface of the chaperone site in the chaperone activity of trigger factor
Authors: Fan Dongjie , Cao Shunan , Zhou Qiming , Zhang You , Yue Lei , Han Chang , Yang Bo , Wang Yu , Ma Zhuo , Zhu Lingxiang , Liu Chuanpeng 
Published: June 2018

ABSTRACTTrigger factor (TF) is a key component of the prokaryotic chaperone network, which is involved in many basic cellular processes, such as protein folding, protein trafficking, and ribosome assembly. The major chaperone site of TF has a cradle‐like structure in which protein substrate may fold without interference from other proteins. Here, we investigated in vivo and in vitro the roles of hydrophobic and charged patches on the edge and interior of cradle during TF‐assisted protein folding. Our results showed that most of the surface of the cradle was involved in TF‐assisted protein folding, which was larger than found in early studies. Although the inner surface of cradle was mostly hydrophobic, both hydrophobic and electrostatic patches were indispensable for TF to facilitate correct protein folding. However, hydrophobic patches were more important for the antiaggregation activity of TF. Furthermore, it was found that the patches on the surface of cradle were involved in TF‐assisted protein folding in a spatial and temporal order. These results suggest that the folding‐favorable interface between the cradle and substrate was dynamic during TF‐assisted protein folding, which enabled TF to be involved in the folding of substrate in an aggressive manner rather than acting as a classic holdase.—Fan, D., Cao, S., Zhou, Q., Zhang, Y., Yue, L., Han, C., Yang, B., Wang, Y., Ma, Z., Zhu, L., Liu, C. Exploring the roles of substrate‐binding surface of the chaperone site in the chaperone activity of trigger factor. FASEB J. 32, 6655–6665 (2018). www.fasebj.org
Angiotensin II receptor I blockade prevents stenosis of tissue engineered vascular grafts
Authors: de Dios Ruiz‐Rosado Juan , Lee Yong‐Ung , Mahler Nathan , Yi Tai , Robledo‐Avila Frank , Martinez‐Saucedo Diana , Lee Avione Y. , Shoji Toshihiro , Heuer Eric , Yates Andrew R. , Pober Jordan S. , Shinoka Toshiharu , Partida‐Sanchez Santiago , Breuer Christopher K. 
Published: June 2018

ABSTRACTWe previously developed a tissue‐engineered vascular graft (TEVG) made by seeding autologous cells onto a biodegradable tubular scaffold, in an attempt to create a living vascular graft with growth potential for use in children undergoing congenital heart surgery. Results of our clinical trial showed that the TEVG possesses growth capacity but that its widespread clinical use is not yet advisable due to the high incidence of TEVG stenosis. In animal models, TEVG stenosis is caused by increased monocytic cell recruitment and its classic (“M1”) activation. Here, we report on the source and regulation of these monocytes. TEVGs were implanted in wild‐type, CCR2 knockout (Ccr2−/−), splenectomized, and spleen graft recipient mice. We found that bone marrow—derived Ly6C+hi monocytes released from sequestration by the spleen are the source of mononuclear cells infiltrating the TEVG during the acute phase of neovessel formation. Furthermore, short‐term administration of losartan (0.6 g/L, 2 wk), an angiotensin II type 1 receptor antagonist, significantly reduced the macrophage populations (Ly6C+/−/F480+) in the scaffolds and improved long‐term patency in TEVGs. Notably, the combined effect of bone marrow‐derived mononuclear cell seeding with short‐term losartan treatment completely prevented the development of TEVG stenosis. Our results provide support for pharmacologic treatment with losartan as a strategy to modulate monocyte infiltration into the grafts and thus prevent TEVG stenosis.—Ruiz‐Rosado, J. D. D., Lee, Y.‐U., Mahler, N., Yi, T., Robledo‐Avila, F.,Martinez‐Saucedo,D.,Lee,A.Y.,Shoji,T., Heuer, E.,Yates,A.R., Pober, J. S., Shinoka,T., Partida‐Sanchez, S., Breuer, C. K. Angiotensin II receptor I blockade prevents stenosis of tissue engineered vascular grafts. FASEB J. 32, 6822‐6832 (2018). www.fasebj.org
O‐Glycosylation‐mediated signaling circuit drives metastatic castration‐resistant prostate cancer
Authors: Tzeng Sheue‐Fen , Tsai Chin‐Hsien , Chao Tai‐Kuang , Chou Yu‐Ching , Yang Yu‐Chih , Tsai Mong‐Hsun , Cha Tai‐Lung , Hsiao Pei‐Wen 
Published: June 2018

ABSTRACTDisseminated castration‐resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen‐deprivation therapy. The increase in human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2‐targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression. Using transcriptomic analysis of prostate cancer data sets, histopathologic examination of clinical specimens, and in vivo experiments of xenograft models, we reveal in this study a coordinated increase in glycan‐binding protein, galectin‐4, specific glycosyltransferases of core 1 synthase, glycoprotein‐N‐acetylgalactosamine 3‐β‐galactosyltransferase 1 (C1GALT1) and ST3 β‐galactoside α‐2,3‐sialyltransferase 1 (ST3GAL1), and resulting mucin‐type O‐glycans during the progression of CRPC. Furthermore, galectin‐4 engaged with C1GALT1‐dependent O‐glycans to promote castration resistance and metastasis by activating receptor tyrosine kinase signaling and cancer cell sternness properties mediated by SRY‐box 9 (SOX9). This galectin‐glycan interaction up‐regulated the MYC‐dependent expression of C1GALT1 and ST3GAL1, which altered cellular mucin‐type O‐glycosylation to allow for galectin‐4 binding. In clinical prostate cancer, high‐level expression of C1GALT1 and galectin‐4 together predict poor overall survival compared with low‐level expression of C1GALT1 and galectin‐4. In summary, MYC regulates abnormal O‐glycosylation, thus priming cells for binding to galectin‐4 and downstream signaling, which promotes castration resistance and metastasis.—Tzeng, S.‐F., Tsai, C.‐H., Chao, T.‐K., Chou, Y.‐C., Yang, Y.‐C., Tsai, M.‐H., Cha, T.‐L., Hsiao, P.‐W. O‐Glycosylation‐mediated signaling circuit drives metastatic castration‐resistant prostate cancer. FASEB J. 32, 6869–6882 (2018). www.fasebj.org
Mechanisms leading to T-cell activation in drug hypersensitivity
Authors: Meng Xiaoli , Yerly Daniel , Naisbitt Dean J. 
Published: June 2018

Purpose of review
Delayed-type or nonimmediate drug hypersensitivity reactions often involve the activation of drug-specific T cells. As such, the molecular initiating event is an interaction between HLA proteins, HLA-binding peptides and the drug. For many years, the formation of covalently modified drug protein adducts was assumed to be a prerequisite for T-cell activation. The purpose of this article is to review recent studies using human PBMC, T-cell lines and clones, which show that drugs are in fact loaded onto HLA molecules in different forms to activate T cells.

Recent findings
We now know that protein-reactive drugs such as β-lactam antibiotics activate T cells via direct noncovalent interactions with HLA or HLA-binding peptides, direct covalent modification of HLA-binding peptides and covalent binding of non-HLA associated proteins. Adducts formed inside and outside of the cells undergo protein processing to generate HLA-binding peptides that are assumed to contain the drug modification. Studies using synthetic stable (e.g. oxypurinol) and reactive (e.g. nitroso sulfamethoxazole) metabolites show that metabolites activate T cells via the same pathways. A variety of drugs with different structural features have also been shown to activate T cells though a direct HLA-binding interaction. Of note, abacavir behaves in an unexpected way, binding deep in the peptide binding cleft of one HLA, selectively activating CD8+ T cells.

Summary
In-vitro studies have revealed that a number of drug HLA-binding interactions lead to the activation of T cells. These can be categorized according to two hypotheses, namely hapten and pharmacological interactions. As we move forward with the development of diagnostic and predictive T-cell assays, it is critical to reach a consensus that direct drug HLA binding and the formation of drug protein adducts are important events for T-cell activation.
Etiology of Global Corneal Blindness and Current Practices of Corneal Transplantation: A Focused Review
Authors: Mathews Priya M. , Lindsley Kristina , Aldave Anthony J. , Akpek Esen K. 
Published: June 2018

Purpose:
The purpose of this focused review was to explore the etiologies of corneal blindness worldwide and compare them with the indications and type of keratoplasties (eg, full-thickness penetrating keratoplasty, anterior lamellar keratoplasty, or endothelial keratoplasty) performed.

Methods:
A literature search of the articles published in the top 10 journals (based on the Altmetrics score) relevant to corneal transplantation within the past 20 years was performed to determine how the focus within corneal transplantation has changed over time. These data were compared with the prevalence and etiology of corneal blindness in each respective region worldwide.

Results:
The leading etiologies of corneal blindness worldwide are primarily due to anterior corneal pathology with a normal endothelium, and the prevalence is highest in developing countries. In addition, the number and type of corneal transplantations performed globally indicate that current practices are disproportionately skewed in favor of endothelial keratoplasty, which is targeted for the pathology prevalent in developed countries. Despite the large number of individuals who would benefit from anterior lamellar keratoplasty, this technique seems to be infrequently performed.

Conclusions:
Most corneal blindness worldwide is secondary to anterior corneal pathology because of infections and trauma. However, this does not align with the current trends and practices in the field of corneal transplantation. We discuss potential solutions to address the current leading causes of global corneal blindness, including increasing the number of anterior lamellar keratoplasties performed, using long-term preserved corneas by trained surgeons, and improving eye bank handling and distribution of procured tissues.
Combined Hookwire and Methylene Blue Localization of Pulmonary Nodules
Authors: Joseph Brady John , Hirsch Reilly Christie , Guay Robert , Dasika Uday 
Published: June 2018

Objective Because of decreased tactile sensation with thoracoscopic approaches to biopsy, localization preoperatively and intraoperatively is important for successful biopsy. Our study evaluated the technique of combined computed tomography-guided hookwire and methylene blue localization. Methods Seventy-five patients from November 2007 to August 2013 who underwent combined Hawkins hookwire and methylene blue localization of 76 total pulmonary nodules before video-assisted thoracic surgery-guided wedge resection were retrospectively reviewed. Multiple patient, nodule, and procedural characteristics were analyzed for correlation with successful wire localization and wire dislodgement. Successful wire localization was defined as absence of lesions requiring re-resection, wire dislodgement necessitating re-resection, or conversion to thoracotomy for localization. Results Seventy-four patients were included in the study (75 pulmonary nodules - 1 patient had 2 lesions localized) and mean ± SD patient age was 65.8 ± 12.1 years and 50% were male. The mean ± SD largest nodule diameter was 14.6 ± 7.4 mm and 29.3% of these were subcentimeter pulmonary nodules. Increased age and history of malignancy were associated with malignant diagnoses ( P = 0.037 and 0.009, respectively) Successful wire localization was present in 86.4% of patients. Lesions with lower mean distance to the pleura correlated with successful localization ( P = 0.002). Wire dislodgement was present in 9.3% (7 patients) with 4 (5.3%) of these necessitating need for re-resection to establish pathologic diagnosis. Albeit wire dislodgement, 57.4% (4/7) still had successful thoracoscopic localization. Conclusions This study demonstrates that utilization of Hawkins hookwire in combination with methylene blue injection is an effective method to successfully localize pulmonary nodules for thoracoscopic wedge resection and should prompt further investigation for its utilization.
Using Lean to Enhance Heart Failure Patient Identification Processes and Increase Core Measure Scores
Authors: Hunt Jennifer R. , Ouellette Kelli Jo , Reece Michelle 
Published: June 2018

Background:
Heart failure (HF) is the leading cause of hospitalization among older adults in the United States. Health systems target readmission rates for quality improvement and cost reduction.

Local Problem:
Heart failure core measure (CM) scores at our medical center were lower than the national average, and methods for capturing the appropriate documentation on HF patients to ensure CM compliance were not clear.

Methods:
An interdisciplinary team determined barriers to increasing CM scores, gathered baseline data, and identified gaps in the existing process.

Interventions:
The team implemented an accurate reporting system and error-proofing process, redesigned the process for identifying patients admitted with a HF diagnosis, and developed a patient appointment section before discharge in the electronic medical record.

Results:
There was a decrease in readmissions within 30 days of implementation from 12% to 8%, and HF CM compliance score increased from 88% to 100%. The percentage of HF patients not identified during hospitalization decreased from 17% to 0%. Heart failure patients discharged with a 7-day follow-up appointment increased from 88% to 98%.

Conclusion:
Through implementation of an interdisciplinary-led process improvement and lean methodologies, metrics and CMs were achieved.
Longer Duration of Urinary Catheterization Increases Catheter-Associated Urinary Tract Infection in PICU
Authors: Fukuoka Kahoru , Furuichi Mihoko , Ito Kenta , Morikawa Yoshihiko , Watanabe Ichiro , Shimizu Naoki , Horikoshi Yuho 
Published: June 2018

Objectives:
Catheter-associated urinary tract infections account for 30% of healthcare-associated infections. To date, few studies have addressed pediatric catheter-associated urinary tract infection in PICUs. The aim of our study was to assess the risk of catheter-associated urinary tract infection in relation to the duration of catheterization in the PICU.

Design:
Retrospective cohort study.

Setting:
PICU at a tertiary children’s hospital.

Patients:
Our study was conducted between April 2012 and June 2015 at Tokyo Metropolitan Children’s Medical Center in Japan. Children in the PICU with an urethral catheter were included. Catheter-associated urinary tract infection cases were defined according to the National Healthcare Safety Network criteria. The patients’ demographic data and isolated organisms were reviewed. Duration of catheterization and the catheter-associated urinary tract infection occurrence rate were analyzed.

Interventions:
None.

Measurements and Main Results:
Among 1,890 catheterizations, 23 catheter-associated urinary tract infection cases were identified. The overall occurrence rate was 2.35/1,000 catheter-days. Among the patients with catheter-associated urinary tract infection, 13 were boys. The median age was 11 months (interquartile range, 7–35 mo), and the median duration of catheterization was 7 days (interquartile range, 5–12 d). The isolated bacteria were Escherichia coli (26.5%), Enterococcus faecalis (17.6%), and Klebsiella pneumoniae (11.8%). Two species were isolated in each of 11 cases (47.8%). Each additional day of catheterization increased the risk of catheter-associated urinary tract infection (odds ratio, 1.06; 95% CI, 1.02–1.10, and odds ratio adjusted for contact precaution status and surgical procedures was 1.05; 95% CI, 1.01–1.09).

Conclusions:
Longer duration of catheterization increased the risk of catheter-associated urinary tract infection by 5% each day at the PICU. Prompt removal of the urethral catheter is strongly recommended whenever feasible.
Caring for Pediatric Patients With Epidermolysis Bullosa in the Emergency Department
Authors: Jenkinson Helena A. , Lundgren Ashley D. , Levy Moise L. , Diaz Lucia Z. 
Published: June 2018

Abstract
Epidermolysis bullosa (EB) refers to a heterogeneous group of genetic disorders characterized by epithelial fragility. We provide guidelines for management of pediatric patients with EB in the emergency department based on a review of literature, as well as insights from our own experiences caring for patients with EB. The purpose of the guidelines proposed is prevention of avoidable iatrogenic trauma to the skin and mucosa of patients with EB who are presenting to the emergency department for a variety of reasons.
Just-in-Time Training for Intraosseous Needle Placement and Defibrillator Use in a Pediatric Emergency Department
Authors: Itoh Taichi , Lee-Jayaram Jannet , Fang Rui , Hong Travis , Berg Benjamin 
Published: June 2018

ObjectivesJust-in-time training (JITT) is a method of simulation-based training where the training occurs within the clinical environment in a concise manner. Just-in-time training has shown effects at the learner, patient, and system-wide levels. We evaluated a JITT curriculum for the procedures of intraosseous (IO) needle placement and defibrillator use in a pediatric emergency department (ED) by comparing the trainees' comfort level in performing those procedures independently (Kirkpatrick level 2a) and trainees' knowledge of the procedures/equipment (Kirkpatrick level 2b) before and after the JITT.MethodsThe study enrolled all fourth year medical students and residents (family medicine and pediatrics) who rotated through a children's hospital ED. The JITT curriculum included group discussion on storage locations of procedure equipment in the ED and clinical indications/contraindications followed by hands-on procedure training. One of 2 attending physicians facilitated the 10- to 20-minute JITT in the ED during their shifts. Trainees completed an anonymous survey to delineate medical training level, previous procedure experiences, procedure-related knowledge, and comfort level to perform the procedures independently. Identical surveys were completed before and after the JITT. The data were analyzed using percentage for categorical variables. For comparisons between pre-JITT and post-JITT survey data, χ2tests or Fisher exact tests were used.ResultsThere were 65 surveys included (34 pre-JITT and 31 post-JITT surveys). The comfort level to perform procedures independently increased from pre-JITT 0% to post-JITT 48% (P< 0.001) for IO needle placement and from pre-JITT 3% to post-JITT 32% (P= 0.0016) for defibrillator use. The procedure-related knowledge also increased by ##greater than or equal to 50% post-JITT (P< 0.0001).ConclusionsOur JITT curriculum significantly increased the comfort level of the trainees to perform IO needle insertion and defibrillator use independently. Procedure-related knowledge also increased. By increasing their comfort to perform these procedures independently, we aim to increase the likelihood that trainees can be competent contributing members of an acute medical response team in these respective roles.
Translational models of infection prevention and control: lessons from studying high risk aging populations
Authors: Mody Lona 
Published: June 2018

Purpose of review
The present review describes our research experiences and efforts in advancing the field of infection prevention and control in nursing facilities including postacute and long-term care settings.

Recent findings
There are over two million infections in postacute and long-term care settings each year in the United States and $4 billion in associated costs. To define a target group most amenable to infection prevention and control interventions, we sought to quantify the relation between indwelling device use and microbial colonization in nursing facility patients. Using various methodologies including survey methods, observational epidemiology, randomized controlled studies, and collaboratives, we showed that (1) indwelling device type is related to the site of multidrug-resistant organism (MDRO) colonization; (2) multianatomic site colonization with MDROs is common; (3) community-associated methicillin-resistant Staphylococcus aureus (MRSA) appeared in the nursing facility setting almost immediately following its emergence in acute care; (4) MDRO prevalence and catheter-associated infection rates can be reduced through a multimodal targeted infection prevention intervention; and (5) using a collaborative approach, such an intervention can be successfully scaled up.

Summary
Our work advances the infection prevention field through translational research utilizing various methodologies, including quantitative and qualitative surveys, patient-oriented randomized controlled trials, and clinical microbiologic and molecular methods. The resulting interventions employ patient-oriented methods to reduce infections and antimicrobial resistance, and with partnerships from major national entities, can be implemented nationally.
Liver Perfusate Natural Killer Cells From Deceased Brain Donors and Association With Acute Cellular Rejection After Liver Transplantation: A Time-to-Rejection Analysis
Authors: Pagano Duilio , Badami Ester , Conaldi Pier Giulio , Seidita Aurelio , Tuzzolino Fabio , Barbàra Marco , di Francesco Fabrizio , Tropea Alessandro , Liotta Rosa , Chiarello Gaia , Luca Angelo , Gruttadauria Salvatore 
Published: June 2018

Background
The ability to predict which recipients will successfully complete their posttransplant clinical course, which is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates could help identify risk factors portending adverse LT outcomes.

Methods
Liver perfusates were collected during the back-table surgical time after the procurement procedures for donors after brain death. Lymphocytic concentrations and phenotypes were matched with donors after brain death characteristics and indications, timing, surgical techniques, outcomes, and biopsy-proven acute cellular rejections (ACRs) in 46 adult recipients who underwent LT between 2010 and 2014 at our institute. Cox regression models were used to study relevant risk factors in order to estimate hazard ratios for episodes of rejection after LT.

Results
Percentage of NK cells was significantly associated with donor age (P = 0.05) and the percentage of NK T cellular subset (P = 0.001). The length of follow-up after LT was 41.0 ± 20.9 months, and 11 (23.9%) recipients experienced biopsy-proven ACR. At time-to-rejection proportional regression analysis, a cutoff value of 33.7% was optimal, with a sensitivity of 1, specificity of 0.57, and positive and negative predictive values of 0.42 and 1, respectively. The liver perfusate NK cell subset was strongly associated with biopsy-proven ACR (hazard ratio, 10.7; P = 0.02).

Conclusions
Liver perfusate cytofluorimetric phenotyping may contribute as a targeted preoperative tool to predict the risk of ACR, and as clinical test in translational studies that aim to improve donor allograft procurement and transplant outcomes.