bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Activity Monitoring in Extremely Obese Adolescents From the Teen-LABORATORIES Study
Authors: Jeffreys Renee M. , Inge Thomas H. , Jenkins Todd M. , King Wendy C. , Oruc Vedran , Douglas Andrew D. , Bray Molly S. 
Published: September 2014

Background:The accuracy of physical activity (PA) monitors to discriminate between PA, sedentary behavior, and nonwear in extremely obese (EO) adolescents is unknown.Methods:Twenty-five subjects (9 male/16 female; age = 16.5 ± 2.0 y; BMI = 51 ± 8 kg/m2) wore 3 activity monitors (StepWatch [SAM], Actical [AC], Actiheart [AH]) during a 400-m walk test (400MWT), 2 standardized PA bouts of varying duration, and 1 sedentary bout.Results:For the 400MWT, percent error between observed and monitor-recorded steps was 5.5 ± 7.1% and 82.1 ± 38.6% for the SAM and AC steps, respectively (observed vs. SAM steps: −17.2 ± 22.2 steps; observed vs. AC steps: −264.5 ± 124.8 steps). All activity monitors were able to differentiate between PA and sedentary bouts, but only SAM steps and AH heart rate were significantly different between sedentary behavior and nonwear (P < .001). For all monitors, sedentary behavior was characterized by bouts of zero steps/counts punctuated by intermittent activity steps/counts; nonwear was represented almost exclusively by zero steps/counts.Conclusion:Of all monitors tested, the SAM was most accurate in terms of counting steps and differentiating levels of PA and thus, most appropriate for EO adolescents. The ability to accurately characterize PA intensity in EO adolescents critically depends on activity monitor selection.
Intracellular Vibrio parahaemolyticus Escapes the Vacuole and Establishes a Replicative Niche in the Cytosol of Epithelial Cells
Authors: de Souza Santos Marcela , Orth Kim 
Published: September 2014

ABSTRACT

Vibrio parahaemolyticus
is a globally disseminated Gram-negative marine bacterium and the leading cause of seafood-borne acute gastroenteritis. Pathogenic bacterial isolates encode two type III secretion systems (T3SS), with the second system (T3SS2) considered the main virulence factor in mammalian hosts. For many decades,
V. parahaemolyticus
has been studied as an exclusively extracellular bacterium. However, the recent characterization of the T3SS2 effector protein VopC has suggested that this pathogen has the ability to invade, survive, and replicate within epithelial cells. Herein, we characterize this intracellular lifestyle in detail. We show that following internalization,
V. parahaemolyticus
is contained in vacuoles that develop into early endosomes, which subsequently mature into late endosomes.
V. parahaemolyticus
then escapes into the cytoplasm prior to vacuolar fusion with lysosomes. Vacuolar acidification is an important trigger for this escape. The cytoplasm serves as the pathogen’s primary intracellular replicative niche; cytosolic replication is rapid and robust, with cells often containing over 150 bacteria by the time of cell lysis. These results show how
V. parahaemolyticus
successfully establishes an intracellular lifestyle that could contribute to its survival and dissemination during infection.

IMPORTANCE
The marine bacterium
V. parahaemolyticus
is the leading cause worldwide of seafood-borne acute gastroenteritis. For decades, the pathogen has been studied exclusively as an extracellular bacterium. However, recent results have revealed the pathogen’s ability to invade and replicate within host cells. The present study is the first characterization of the
V. parahaemolyticus
’ intracellular lifestyle. Upon internalization,
V. parahaemolyticus
is contained in a vacuole that would in the normal course of events ultimately fuse with a lysosome, degrading the vacuole’s contents. The bacterium subverts this pathway, escaping into the cytoplasm prior to lysosomal fusion. Once in the cytoplasm, it replicates prolifically. Our study provides new insights into the strategies used by this globally disseminated pathogen to survive and proliferate within its host.
The Plant Pathogen Xanthomonas campestris pv.
campestris
Exploits
N
-Acetylglucosamine during Infection
Authors: Boulanger Alice , Zischek Claudine , Lautier Martine , Jamet Stevie , Rival Pauline , Carrère Sébastien , Arlat Matthieu , Lauber Emmanuelle 
Published: September 2014

ABSTRACT

N
-Acetylglucosamine (GlcNAc), the main component of chitin and a major constituent of bacterial peptidoglycan, is present only in trace amounts in plants, in contrast to the huge amount of various sugars that compose the polysaccharides of the plant cell wall. Thus, GlcNAc has not previously been considered a substrate exploited by phytopathogenic bacteria during plant infection.
Xanthomonas campestris
pv.
campestris
, the causal agent of black rot disease of
Brassica
plants, expresses a carbohydrate utilization system devoted to GlcNAc exploitation. In addition to genes involved in GlcNAc catabolism, this system codes for four TonB-dependent outer membrane transporters (TBDTs) and eight glycoside hydrolases. Expression of all these genes is under the control of GlcNAc.
In vitro
experiments showed that
X. campestris
pv.
campestris
exploits chitooligosaccharides, and there is indirect evidence that during the early stationary phase,
X. campestris
pv.
campestris
recycles bacterium-derived peptidoglycan/muropeptides. Results obtained also suggest that during plant infection and during growth in cabbage xylem sap,
X. campestris
pv.
campestris
encounters and metabolizes plant-derived GlcNAc-containing molecules. Specific TBDTs seem to be preferentially involved in the consumption of all these plant-, fungus- and bacterium-derived GlcNAc-containing molecules. This is the first evidence of GlcNAc consumption during infection by a phytopathogenic bacterium. Interestingly,
N
-glycans from plant
N
-glycosylated proteins are proposed to be substrates for glycoside hydrolases belonging to the
X. campestris
pv.
campestris
GlcNAc exploitation system. This observation extends the range of sources of GlcNAc metabolized by phytopathogenic bacteria during their life cycle.

IMPORTANCE
Despite the central role of
N
-acetylglucosamine (GlcNAc) in nature, there is no evidence that phytopathogenic bacteria metabolize this compound during plant infection. Results obtained here suggest that
Xanthomonas campestris
pv.
campestris
, the causal agent of black rot disease on
Brassica
, encounters and metabolizes GlcNAc
in planta
and
in vitro
. Active and specific outer membrane transporters belonging to the TonB-dependent transporters family are proposed to import GlcNAc-containing complex molecules from the host, from the bacterium, and/or from the environment, and bacterial glycoside hydrolases induced by GlcNAc participate in their degradation. Our results extend the range of sources of GlcNAc metabolized by this phytopathogenic bacterium during its life cycle to include chitooligosaccharides that could originate from fungi or insects present in the plant environment, muropeptides leached during peptidoglycan recycling and bacterial lysis, and
N-
glycans from plant
N
-glycosylated proteins present in the plant cell wall as well as in xylem sap.
Relaxed Substrate Specificity Leads to Extensive tRNA Mischarging by Streptococcus pneumoniae Class I and Class II Aminoacyl-tRNA Synthetases
Authors: Shepherd Jennifer , Ibba Michael 
Published: September 2014

ABSTRACT

Aminoacyl-tRNA synthetases provide the first step in protein synthesis quality control by discriminating cognate from noncognate amino acid and tRNA substrates. While substrate specificity is enhanced in many instances by
cis-
and
trans
-editing pathways, it has been revealed that in organisms such as
Streptococcus pneumoniae
some aminoacyl-tRNA synthetases display significant tRNA mischarging activity. To investigate the extent of tRNA mischarging in this pathogen, the aminoacylation profiles of class I isoleucyl-tRNA synthetase (IleRS) and class II lysyl-tRNA synthetase (LysRS) were determined. Pneumococcal IleRS mischarged tRNA
Ile
with both Val, as demonstrated in other bacteria, and Leu in a tRNA sequence-dependent manner. IleRS substrate specificity was achieved in an editing-independent manner, indicating that tRNA mischarging would only be significant under growth conditions where Ile is depleted. Pneumococcal LysRS was found to misaminoacylate tRNA
Lys
with Ala and to a lesser extent Thr and Ser, with mischarging efficiency modulated by the presence of an unusual U4:G69 wobble pair in the acceptor stems of both pneumococcal tRNA
Lys
isoacceptors. Addition of the
trans-
editing factor MurM, which also functions in peptidoglycan synthesis, reduced Ala-tRNA
Lys
production by LysRS, providing evidence for cross talk between the protein synthesis and cell wall biogenesis pathways. Mischarging of tRNA
Lys
by AlaRS was also observed, and this would provide additional potential MurM substrates. More broadly, the extensive mischarging activities now described for a number of
Streptococcus pneumoniae
aminoacyl-tRNA synthetases suggest that adaptive misaminoacylation may contribute significantly to the viability of this pathogen during amino acid starvation.

IMPORTANCE
Streptococcus pneumoniae
is a common causative agent of several debilitating and potentially life-threatening infections, such as pneumonia, meningitis, and infectious endocarditis. Such infections are increasingly difficult to treat due to widespread development of penicillin resistance. High-level penicillin resistance is known to depend in part upon MurM, a protein involved in both aminoacyl-tRNA-dependent synthesis of indirect amino acid cross-linkages within cell wall peptidoglycan and in translation quality control. The involvement of MurM in both protein synthesis and antibiotic resistance identify it as a potential target for the development of new and potent antibiotics for pneumococcal infections. The goals of this work were to identify and characterize
S. pneumoniae
pathways that can synthesize mischarged tRNAs and to relate these activities to expected changes in protein and peptidoglycan biosynthesis during antibiotic and nutritional stress.
PCTAIRE1 Phosphorylates p27 and Regulates Mitosis in Cancer Cells
Authors: Yanagi Teruki , Krajewska Maryla , Matsuzawa Shu-ichi , Reed John C. 
Published: September 2014

Abstract
PCTAIRE1 is distant relative of the cyclin-dependent kinase family that has been implicated in spermatogenesis and neuronal development, but it has not been studied in cancer. Here, we report that PCTAIRE1 is expressed in prostate, breast, and cervical cancer cells, where its RNAi-mediated silencing causes growth inhibition with aberrant mitosis due to defects in centrosome dynamics. PCTAIRE1 was not similarly involved in proliferation of nontransformed cells, including diploid human IMR-90 fibroblasts. Through yeast two-hybrid screening, we identified tumor suppressor p27 as a PCTAIRE1 interactor. In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PCTAIRE1 silencing modulated Ser10 phosphorylation on p27 and led to its accumulation in cancer cells but not in nontransformed cells. In a mouse xenograft model of PPC1 prostate cancer, conditional silencing of PCTAIRE1 restored p27 protein expression and suppressed tumor growth. Mechanistic studies in HeLa cells showed that PCTAIRE1 phosphorylates p27 during the S and M phases of the cell cycle. Notably, p27 silencing was sufficient to rescue cells from mitotic arrest caused by PCTAIRE1 silencing. Clinically, PCTAIRE1 was highly expressed in primary breast and prostate tumors compared with adjacent normal epithelial tissues. Together our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth, suggesting PCTAIRE1 as a candidate cancer therapeutic target. Cancer Res; 74(20); 5795–807. ©2014 AACR.
Genetic Associations in Classical Hodgkin Lymphoma: A Systematic Review and Insights into Susceptibility Mechanisms
Authors: Kushekhar Kushi , van den Berg Anke , Nolte Ilja , Hepkema Bouke , Visser Lydia , Diepstra Arjan 
Published: September 2014

Abstract
Both targeted and genome-wide studies have revealed genetic associations for susceptibility, prognosis, and treatment-induced secondary malignancies and toxicities in classical Hodgkin lymphoma (cHL). This review gives a systematic and comprehensive overview of significant associations and places them into a biologic context. The strongest susceptibility polymorphisms have been found for the human leukocyte antigen (HLA) genes. These associations are specific for cHL overall or for subgroups based on tumor cell Epstein–Barr virus (EBV) status. These findings strongly suggest that EBV-specific immune responses influence cHL susceptibility in EBV+ cHL and that immune responses targeting other tumor-associated antigens are important in EBV− cHL. Accordingly, most of the numerous other susceptibility loci map to genes that affect functionality of the immune system, underscoring the crucial role of the immune system in cHL development. The number of association studies on cHL prognosis is limited with one consistent association for the drug-metabolizing UGT1A1 gene. PRDM1 is associated with radiation-induced secondary malignancies and a small number of genes are associated with treatment-related toxicities. In conclusion, most loci showing genetic associations in cHL harbor genes with a potential functional relevance for cHL susceptibility. Cancer Epidemiol Biomarkers Prev; 23(12); 2737–47. ©2014 AACR.
A Chemically Defined Trifunctional Antibody–Cytokine–Drug Conjugate with Potent Antitumor Activity
Authors: List Thomas , Casi Giulio , Neri Dario 
Published: September 2014

Abstract
The combination of immunostimulatory agents with cytotoxic drugs is emerging as a promising approach for potentially curative tumor therapy, but advances in this field are hindered by the requirement of testing individual combination partners as single agents in dedicated clinical studies, often with suboptimal efficacy. Here, we describe for the first time a novel multipayload class of targeted drugs, the immunocytokine–drug conjugates (IDC), which combine a tumor-homing antibody, a cytotoxic drug, and a proinflammatory cytokine in the same molecular entity. In particular, the IL2 cytokine and the disulfide-linked maytansinoid DM1 microtubular inhibitor could be coupled to the F8 antibody, directed against the alternatively spliced EDA domain of fibronectin, in a site-specific manner, yielding a chemically defined product with selective tumor-homing performance and potent anticancer activity in vivo, as tested in two different immunocompetent mouse models. Mol Cancer Ther; 13(11); 2641–52. ©2014 AACR.
Relocation of CLIC1 Promotes Tumor Cell Invasion and Colonization of Fibrin
Authors: Gurski Lisa A. , Knowles Lynn M. , Basse Per H. , Maranchie Jodi K. , Watkins Simon C. , Pilch Jan 
Published: September 2014

AbstractChloride intracellular channel 1 (CLIC1) has been shown to be upregulated in various malignancies but its exact function remains unclear. Here, it is revealed that CLIC1 is critical for the stability of invadopodia in endothelial and tumor cells embedded in a 3-dimensional (3D) matrix of fibrin. Invadopodia stability was associated with the capacity of CLIC1 to induce stress fiber and fibronectin matrix formation following its β3 integrin (ITGB3)-mediated recruitment into invadopodia. This pathway, in turn, was relevant for fibrin colonization as well as slug (SNAI2) expression and correlated with a significant role of CLIC1 in metastasis in vivo. Mechanistically, a reduction of myosin light chain kinase (MYLK) in CLIC1-depleted as well as β3 integrin-depleted cells suggests an important role of CLIC1 for integrin-mediated actomyosin dynamics in cells embedded in fibrin. Overall, these results indicate that CLIC1 is an important contributor to tumor invasion, metastasis, and angiogenesis.Implications: This study uncovers an important new function of CLIC1 in the regulation of cell–extracellular matrix interactions and ability of tumor cells to metastasize to distant organs. Mol Cancer Res; 13(2); 273–80. ©2014 AACR.
Natural History and Outcome After Treatment of Unruptured Intradural Fusiform Aneurysms
Authors: Sacho Raphael H. , Saliou Guillaume , Kostynskyy Alex , Menezes Ravi , Tymianski Michael , Krings Timo , Radovanovic Ivan , Terbrugge Karel , Rinkel Gabriel J.E. , Willinsky Robert 
Published: September 2014

Background and Purpose—
Management of unruptured fusiform intracranial aneurysms is controversial because of the paucity of natural history data. We studied their natural history and outcome after treatment.

Methods—
We reviewed our neurovascular database from January 2000 to October 2013. Inclusion criteria were unruptured, intradural fusiform aneurysms with a diameter of <2.5 cm. Criteria were developed to define atherosclerotic aneurysms. For outcome assessment, we used the modified Ranking Scale and aneurysm measurements on serial imaging. Mann–Whittney (continuous) and Fisher exact (categorical) tests were used for risk factor analysis.

Results—
For nonatherosclerotic aneurysms (96 patients; 193 person-years follow-up), 1 patient died (rupture) during follow-up (mortality, 0.51% per year) and 8 patients (10%) showed aneurysm progression (risk, 1.6% per year). Risk factors for progression were maximum diameter (>7 mm; odds ratio, 12; 95% confidence interval, 1.4–104) and symptomatic clinical presentation (odds ratio, 16; 95% confidence interval, 3.1–81.4). Of the 23 treated patients, 3 had died (mortality, 12.5%) and 3 had serious disability (modified Ranking Scale, ≥3; 12.5%). For the atherosclerotic aneurysms (25 patients; 97 person-years follow-up), 5 had died (mortality, 5.2% per year) and 13 of 20 (65%) had aneurysm progression (risk, 12% per year). When compared with patients with nonatherosclerotic aneurysms, case fatality (odds ratio, 19.2; 95% confidence interval, 2.1–172) and aneurysm progression (odds ratio, 17.8; 95% confidence interval, 5.3–56) were higher.

Conclusions—
Nonatherosclerotic fusiform intradural aneurysms have a low risk of adverse outcome within the first few years after diagnosis and remain stable unless symptomatic on presentation or >7 mm in maximum diameter. High risks of treatment should be balanced against this benign natural history. Atherosclerotic aneurysms have a worse natural history and may represent a different disease entity.
Clinical Manifestations of IgG4-Related Disease in the Pharynx
Authors: Reder Lindsay , Della-Torre Emanuel , Stone John H. , Mori Matthew , Song Phillip 
Published: September 2014

Objective: The objective of this report is to characterize IgG4-related disease (IgG4-RD) as it is manifested in the head and neck and describe a series of patients with a rarely described presentation in laryngopharyngeal subsites. Methods: Here, we illustrate the presentation and clinical course of 3 patients with laryngopharyngeal manifestations of IgG4-RD, including the manner of diagnosis and effective treatment. Results: Three patients with laryngopharyngeal lesions were ultimately diagnosed with IgG4-RD after lengthy work-up. The diagnostic criteria and treatment protocols are explained. Conclusion: IgG4-related disease is a fibroinflammatory disorder now described in almost every organ system. The head and neck regions are among the most common areas of involvement, however, reports of laryngopharyngeal involvement are rare. We also summarize current knowledge of this entity and discuss established diagnostic criteria and clinical findings.
Endoscopic Suture Retriever for Endolaryngeal Keel Placement in Treatment of Anterior Glottic Webs
Authors: Beswick Daniel M. , Clark Amelia K. , Bergeron Jennifer , Sung C. Kwang 
Published: September 2014

Introduction: Endoscopic placement of a laryngeal keel has traditionally required the use of a Lichtenberger endo-extralaryngeal needle passer, which is not universally available. We discuss a safe and technically simple alternate technique using an endoscopic suture retriever through a percutaneously placed angiocatheter that obviates the need for the Lichtenberger instrument. Study Design: Case series. Materials and Methods: Two 14-gauge angiocatheters were passed through the anterior neck under telescopic visualization of the larynx. The suture retriever was inserted through the catheter and deployed within the larynx to withdraw a Prolene suture that was threaded through a Silastic keel. The keel was then tied in position over a sterile button on the anterior neck. Results: This procedure was performed on 2 patients with excellent outcomes in both cases. Conclusion: Endoscopic keel placement is a widely used procedure for treating anterior glottic webs and requires suture passage from within the larynx to the anterior neck to secure the keel into position. This is the first report of an exo-endolaryngeal suture retriever for placement of a laryngeal keel. This technique provides a safe, reliable, and efficient alternative to endo-extralaryngeal needle puncture and uses materials that are available in many operating room settings.
Use of Topical Nasal Anesthesia During Flexible Endoscopic Evaluation of Swallowing in Dysphagic Patients
Authors: Fife Tim A. , Butler Susan G. , Langmore Susan E. , Lester Scott , Wright S. Carter , Kemp Shannon , Grace-Martin Karen , Rees Lintzenich Catherine 
Published: September 2014

Objective: This study aimed to determine the effect of topical lidocaine on Penetration-Aspiration Scale (PAS) scores and patient comfort and tolerance of flexible endoscopic evaluation of swallowing (FEES) examinations in dysphagic patients. Methods: Adults with dysphagia referred for swallowing evaluation were recruited to participate in consecutive nonanesthetized and then anesthetized FEES examinations. Under endoscopic visualization, participants consumed 6 swallows consisting of graduated volumes of milk, pudding, and cracker in each condition and recorded their discomfort and tolerance in the 2 conditions. Penetration-Aspiration Scale scores were assigned in blinded fashion for each swallow. Results: Twenty-five adults participated in the study. Although there was no statistically significant effect of anesthesia on PAS scores ( P = .065), the odds of a higher PAS score were 33% higher during anesthetized swallows. The anesthetized condition yielded significantly less discomfort and pain during the examination, significantly less pain and discomfort during insertion and removal of the endoscope, and significantly greater overall tolerance than the nonanesthetized condition. Conclusion: The use of topical lidocaine during FEES may impair swallowing ability in patients with dysphagia, but this result does not achieve statistical significance. Topical nasal anesthesia significantly reduces subjective pain and discomfort and improves tolerance during FEES.