bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multicenter Cohort Study of Treatments and Hospital Outcomes in Neonatal Abstinence Syndrome
Authors: Hall Eric S. , Wexelblatt Scott L. , Crowley Moira , Grow Jennifer L. , Jasin Lisa R. , Klebanoff Mark A. , McClead Richard E. , Meinzen-Derr Jareen , Mohan Vedagiri K. , Stein Howard , Walsh Michele C. 
Published: July 2014

OBJECTIVES:To compare pharmacologic treatment strategies for neonatal abstinence syndrome (NAS) with respect to total duration of opioid treatment and length of inpatient hospital stay.METHODS:We conducted a cohort analysis of late preterm and term neonates who received inpatient pharmacologic treatment of NAS at one of 20 hospitals throughout 6 Ohio regions from January 2012 through July 2013. Physicians managed NAS using 1 of 6 regionally based strategies.RESULTS:Among 547 pharmacologically treated infants, we documented 417 infants managed using an established NAS weaning protocol and 130 patients managed without protocol-driven weaning. Regardless of the treatment opioid chosen, when we accounted for hospital variation, infants receiving protocol-based weans experienced a significantly shorter duration of opioid treatment (17.7 vs 32.1 days, P &lt; .0001) and shorter hospital stay (22.7 vs 32.1 days, P = .004). Among infants receiving protocol-based weaning, there was no difference in the duration of opioid treatment or length of stay when we compared those treated with morphine with those treated with methadone. Additionally, infants treated with phenobarbital were treated with the drug for a longer duration among those following a morphine-based compared with methadone-based weaning protocol. (P ≤ .002).CONCLUSIONS:Use of a stringent protocol to treat NAS, regardless of the initial opioid chosen, reduces the duration of opioid exposure and length of hospital stay. Because the major driver of cost is length of hospitalization, the implications for a reduction in cost of care for NAS management could be substantial.
First glacier‐vibroseismic experiment ‐ results from cold firn of Colle Gnifetti
Authors: Polom Ulrich , Hofstede Coen , Diez Anja , Eisen Olaf 
Published: July 2014

ABSTRACTIn the summer of 2010, a small shallow reflection seismic experiment was carried out on the firn covered cold glacier of Colle Gnifetti, Monte Rosa group, Swiss/Italian Alps. At this site, the physical properties of ice are comparable to polar conditions, which is why this site is often used for methodological tests. The experiment at 4500 m elevation was designed to explore the scope of shallow vibroseis for seismic targets within and below the glacier. A small ELVIS vibrator system was used to generate shear waves and compression waves for SH‐ and P‐wave receiver setups of two profiles. The resulting sections clearly show a boundary from ice to rock around 60 m and deeper structures below the glacier. The deepest features are estimated to be 150 m for the SH‐waves and 220 m for the P‐waves. Reflections could be detected also within the ice overburden, which are preliminarily interpreted as a change of density in the upper 30 m and possibly crystal orientation fabric in the ice column. Furthermore, elastic parameters could be derived from seismic velocities, due to clear basement reflections. The results of this unique experiment enable new insights into the internal structure of ice masses and open a promising new investigation method for sub‐ice structures and properties, such as basal sediments.
TLR4 Activation Enhances the PD-L1–Mediated Tolerogenic Capacity of Colonic CD90+ Stromal Cells
Authors: Beswick Ellen J. , Johnson Jameel R. , Saada Jamal I. , Humen Martin , House Jenifer , Dann Sara , Qiu Suimin , Brasier Allan R. , Powell Don W. , Reyes Victor E. , Pinchuk Irina V. 
Published: July 2014

Abstract
Signaling via programmed death ligand-1 (PD-L1) and PD-L2 is crucial for maintaining peripheral tolerance. CD90+ myofibroblasts/fibroblasts (CMFs) are major programmed cell death-1 (PD-1) ligand–expressing cells in normal human colonic mucosa. CMFs suppress activated CD4+ T cell proliferation via PD-1 ligands. It is not known whether signaling through TLRs contribute to the regulation PD-1 ligands on CMFs upon colonic mucosal tolerance. In this study, we demonstrated that stimulation of TLR4 on human CMFs upregulates PD-L1, but not PD-L2, and reinforces CMF-mediated suppression of CD4+ T cell proliferation and IFN-γ production. TLR4-mediated upregulation of PD-L1 on CMFs involved NF-κB pathways and was JAK2 and MyD88 dependent. MyD88-dependent stimulation of TLR1/2 and TLR5 also upregulated PD-L1 expression on CMFs in culture. PD-L1 expression was drastically decreased in vivo in the colonic mucosa of mice devoid of MyD88. Induction of MyD88 deficiency in CMFs in fibroblast-specific MyD88 conditional knockout mice resulted in a strong increase in a mucosal IFN-γ expression concomitantly with the abrogation of PD-L1 expression in CMFs under homeostasis and epithelial injury induced by dextran sodium sulfate. Together, these data suggest that MyD88-dependent TLR stimulation of CMFs in the normal colonic mucosa may reinforce these cells’ anti-inflammatory capacity and thus contribute to the maintenance of mucosal tolerance.
Ubiquitin-Specific Protease 2b Negatively Regulates IFN-β Production and Antiviral Activity by Targeting TANK-Binding Kinase 1
Authors: Zhang Lei , Zhao Xueying , Zhang Meng , Zhao Wei , Gao Chengjiang 
Published: July 2014

Abstract
TANK-binding kinase 1 (TBK1) is essential for IFN regulatory factor 3 activation and IFN-β production downstream of various innate receptors. However, how TBK1 activation is terminated is not well defined. In this study, we identified ubiquitin-specific protease (USP) 2b as a new negative regulator for TBK1 activation. Overexpression of USP2b inhibited retinoic acid–inducible gene-I–mediated IFN-β signaling; in contrast, knockdown of USP2b expression by small interfering RNA enhanced retinoic acid–inducible gene-I–mediated IFN-β signaling. Coimmunoprecipitation experiments demonstrated that USP2b interacted with TBK1. As a deubiquitinating enzyme, USP2b was demonstrated to cleave K63-linked polyubiquitin chains from TBK1 to inhibit TBK1 kinase activity. Consistent with the inhibitory roles of USP2b on TBK1 activation, knockdown of USP2b significantly inhibited the replication of vesicular stomatitis virus, whereas overexpression of USP2b resulted in enhanced replication of vesicular stomatitis virus. Therefore, our findings demonstrated that USP2b deubiquitinates K63-linked polyubiquitin chains from TBK1 to terminate TBK1 activation and negatively regulate IFN-β signaling and antiviral immune response.
The DNA Sensor, Cyclic GMP–AMP Synthase, Is Essential for Induction of IFN-β during Chlamydia trachomatis Infection
Authors: Zhang Yugen , Yeruva Laxmi , Marinov Anthony , Prantner Daniel , Wyrick Priscilla B. , Lupashin Vladimir , Nagarajan Uma M. 
Published: July 2014

Abstract
IFN-β has been implicated as an effector of oviduct pathology resulting from genital chlamydial infection in the mouse model. In this study, we investigated the role of cytosolic DNA and engagement of DNA sensors in IFN-β expression during chlamydial infection. We determined that three-prime repair exonuclease-1, a host 3′ to 5′ exonuclease, reduced IFN-β expression significantly during chlamydial infection using small interfering RNA and gene knockout fibroblasts, implicating cytosolic DNA as a ligand for this response. The DNA sensor cyclic GMP–AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic GMP–AMP, which binds to the signaling adaptor stimulator of IFN genes (STING) to induce IFN-β expression. We determined that cGAS is required for IFN-β expression during chlamydial infection in multiple cell types. Interestingly, although infected cells deficient for STING or cGAS alone failed to induce IFN-β, coculture of cells depleted for either STING or cGAS rescued IFN-β expression. These data demonstrate that cyclic GMP–AMP produced in infected cGAS+STING− cells can migrate into adjacent cells via gap junctions to function in trans in cGAS−STING+ cells. Furthermore, we observed cGAS localized in punctate regions on the cytosolic side of the chlamydial inclusion membrane in association with STING, indicating that chlamydial DNA is most likely recognized outside the inclusion as infection progresses. These novel findings provide evidence that cGAS-mediated DNA sensing directs IFN-β expression during Chlamydia trachomatis infection and suggest that effectors from infected cells can directly upregulate IFN-β expression in adjacent uninfected cells during in vivo infection, contributing to pathogenesis.
Cutting Edge: Generation of Effector Cells That Localize to Mucosal Tissues and Form Resident Memory CD8 T Cells Is Controlled by mTOR
Authors: Sowell Ryan T. , Rogozinska Magdalena , Nelson Christine E. , Vezys Vaiva , Marzo Amanda L. 
Published: July 2014

Abstract
Mucosal tissues are subject to frequent pathogen exposure and are major sites for transmission of infectious disease. CD8 T cells play a critical role in controlling mucosa-acquired infections even though their migration into mucosal tissues is tightly regulated. The mechanisms and signals that control the formation of tissue-resident memory CD8 T cells are poorly understood; however, one key regulator of memory CD8 T cell differentiation, mammalian target of rapamycin kinase, can be inhibited by rapamycin. We report that, despite enhancing the formation of memory CD8 T cells in secondary lymphoid tissues, rapamycin inhibits the formation of resident memory CD8 T cells in the intestinal and vaginal mucosa. The ability of rapamycin to block the formation of functional resident CD8 T cells in mucosal tissues protected mice from a model of CD8 T cell–mediated lethal intestinal autoimmunity. These findings demonstrate an opposing role for mammalian target of rapamycin in the formation of resident versus nonresident CD8 T cell immunity.
Transcription Factor ABF-1 Suppresses Plasma Cell Differentiation but Facilitates Memory B Cell Formation
Authors: Chiu Yi-Kai , Lin I-Ying , Su Shin-Tang , Wang Kuan-Hsiung , Yang Shii-Yi , Tsai Dong-Yan , Hsieh Yi-Ting , Lin Kuo-I 
Published: July 2014

Abstract
Ag-primed B cells that result from an immune response can form either memory B cells or Ab-secreting plasma cells; however, the molecular machinery that controls this cellular fate is poorly understood. In this study, we show that activated B cell factor-1 (ABF-1), which encodes a basic helix-loop-helix transcriptional repressor, participates in this regulation. ABF-1 was prevalently expressed in purified memory B cells and induced by T follicular helper cell–mediated signals. ABF-1 expression declined by the direct repression of B lymphocyte–induced maturation protein-1 during differentiation. Ectopic expression of ABF-1 reduced the formation of Ab-secreting cells in an in vitro differentiation system of human memory B cells. Accordingly, knockdown of ABF-1 potentiates the formation of Ab-secreting cells. A transgenic mouse that expresses inducible ABF-1 in a B cell–specific manner was generated to demonstrate that the formation of germinal center and memory B cells was augmented by induced ABF-1 in an immune response, whereas the Ag-specific plasma cell response was dampened. This effect was associated with the ability of ABF-1 to limit cell proliferation. Together, our results demonstrate that ABF-1 facilitates formation of memory B cells but prevents plasma cell differentiation.
Essential Role for the Lectin Pathway in Collagen Antibody–Induced Arthritis Revealed through Use of Adenovirus Programming Complement Inhibitor MAp44 Expression
Authors: Banda Nirmal K. , Mehta Gaurav , Kjaer Troels R. , Takahashi Minoru , Schaack Jerome , Morrison Thomas E. , Thiel Steffen , Arend William P. , Holers V. Michael 
Published: July 2014

Abstract
Previous studies using mannose-binding lectin (MBL) and complement C4–deficient mice have suggested that the lectin pathway (LP) is not required for the development of inflammatory arthritis in the collagen Ab–induced arthritis (CAIA) model. MBL, ficolins and collectin-11 are key LP pattern recognition molecules that associate with three serine proteases—MASP-1, MASP-2, and MASP-3—and with two MBL-associated proteins designated sMAP and MBL-associated protein of 44kDA (MAp44). Recent studies have shown that MAp44, an alternatively spliced product of the MASP-1/3 gene, is a competitive inhibitor of the binding of the recognition molecules to all three MASPs. In these studies, we examined the effect of treatment of mice with adenovirus (Ad) programmed to express human MAp44 (AdhMAp44) on the development of CAIA. AdhMAp44 and Ad programming GFP (AdGFP) expression were injected i.p. in C57BL/6 wild type mice prior to the induction of CAIA. AdhMAp44 significantly reduced the clinical disease activity (CDA) score by 81% compared with mice injected with AdGFP. Similarly, histopathologic injury scores for inflammation, pannus, cartilage and bone damage, as well as C3 deposition in the cartilage and synovium, were significantly reduced by AdhMAp44 pretreatment. Mice treated with AdmMAp44, programming expression of mouse MAp44, also showed significantly decreased CDA score and histopathologic injury scores. In addition, administration of AdhMAp44 significantly diminished the severity of Ross River virus–induced arthritis, an LP-dependent model. Our study provides conclusive evidence that an intact complement LP is essential to initiate CAIA, and that MAp44 may be an appropriate treatment for inflammatory arthritis.
Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice
Authors: Lam Roselind S. , O’Brien-Simpson Neil M. , Lenzo Jason C. , Holden James A. , Brammar Gail C. , Walsh Katrina A. , McNaughtan Judith E. , Rowler Dennis K. , Van Rooijen Nico , Reynolds Eric C. 
Published: July 2014

Abstract
The role of the macrophage in the immunopathology of periodontitis has not been well defined. In this study, we show that intraoral inoculation of mice with Porphyromonas gingivalis resulted in infection, alveolar bone resorption, and a significant increase in F4/80+ macrophages in gingival and submandibular lymph node tissues. Macrophage depletion using clodronate-liposomes resulted in a significant reduction in F4/80+ macrophage infiltration of gingival and submandibular lymph node tissues and significantly (p &lt; 0.01) less P. gingivalis–induced bone resorption compared with controls in BALB/c and C57BL/6 mice. In both mouse strains, the P. gingivalis–specific IgG Ab subclass and serum cytokine [IL-4, IL-10, IFN-γ, and IL-12 (p70)] responses were significantly (p &lt; 0.01) lower in the macrophage-depleted groups. Macrophage depletion resulted in a significant reduction in the level of P. gingivalis infection, and the level of P. gingivalis infection was significantly correlated with the level of alveolar bone resorption. M1 macrophages (CD86+), rather than M2 macrophages (CD206+), were the dominant macrophage phenotype of the gingival infiltrate in response to P. gingivalis infection. P. gingivalis induced a significant (p &lt; 0.01) increase in NO production and a small increase in urea concentration, as well as a significant increase in the secretion of IL-1β, IL-6, IL-10, IL-12 (p70), eotaxin, G-CSF, GM-CSF, macrophage chemoattractant protein-1, macrophage inflammatory protein-α and -β, and TNF-α in isolated murine macrophages. In conclusion, P. gingivalis infection induced infiltration of functional/inflammatory M1 macrophages into gingival tissue and alveolar bone resorption. Macrophage depletion reduced P. gingivalis infection and alveolar bone resorption by modulating the host immune response.
Breast Cancer Characteristics and Survival in a Hispanic Population of Costa Rica
Authors: Srur-Rivero Nadia , Cartin-Brenes Mayra 
Published: July 2014

Background Breast cancer characteristics may vary according to the patient's ethnic group. The goal of this cohort study was to evaluate the characteristics of a group of Costa Rican breast cancer patients and their relationship with survival. Methods Age, stage, tumor grade, immunohistochemistry, lymphovascular invasion, recurrence, and survival data on 199 Hispanic patients with breast cancer diagnosis, treated between January 2009 and May 2010, were collected from a single institution in San Jose, Costa Rica. The data were statistically analyzed for significance. Results Median age at diagnosis was 53 years. With a median follow-up of 46.5 months, there was an 88% overall survival rate. Thirty-seven percent of the patients ( p < 0.001) were at stages III and IV during diagnosis. The hormone receptor human epidermal receptor negative phenotype ( HR–HER2–) ( p < 0.001) was present in 17% of the cases. In a multivariate analysis, local (risk ratio, RR: 7.2; confidence interval, CI 95%: 3.8–7.6; p = 0.06) and distant recurrence (RR: 14.9; CI 95%: 7.7–28.9; p = 0.01) showed the strongest association with the probability of death from the disease. Patients with HR–HER2– phenotype tumors reported more local recurrences ( p = 0.04), a higher tumor grade ( p < 0.01), and lower overall survival than patients with other breast cancer phenotypes ( p = 0.01). Conclusions Although this study analyzes a modest number of cases, it is an initial insight into factors that may contribute to differences in breast cancer outcomes among Hispanic women in Costa Rica. The higher proportion of triple negative tumors, advanced stage, and younger median age at diagnosis could contribute to the inferior prognostic described among Hispanic women. There may be a different distribution of tumor subtypes compared to non-Hispanic white women. Further studies are necessary to confirm such findings.
Cardiovascular Risk and Acute Coronary Syndrome in Giant Cell Arteritis: A Population‐Based Retrospective Cohort Study
Authors: Udayakumar Prabhu D. , Chandran Arun K. , Crowson Cynthia S. , Warrington Kenneth J. , Matteson Eric L. 
Published: July 2014

ObjectiveTo assess the occurrence of acute coronary syndrome (ACS) in patients with giant cell arteritis (GCA) compared to subjects without GCA.MethodsWe retrospectively reviewed a population‐based incidence cohort of Olmsted County, Minnesota residents with GCA diagnosed in 1950–2009. We compared this cohort with a cohort of patients without GCA of similar age, sex, and calendar year from the same population.ResultsThe study included 245 patients with GCA and 245 non‐GCA subjects. The mean ± SD Framingham cardiovascular risk score was 30% ± 19% in GCA patients and 34% ± 23% in non‐GCA subjects (P = 0.096) at the incidence/index date. Diabetes mellitus was significantly less common in GCA patients than non‐GCA subjects at the index date. The mean high‐density lipoprotein was higher and triglycerides were lower, with fewer patients taking lipid‐lowering medications in the GCA cohort compared to the non‐GCA cohort at the index date. During followup, no difference between the 2 cohorts was noted in the overall rate of ACS events (hazard ratio 0.74, 95% confidence interval 0.44–1.26). Overall thrombosis in myocardial infarction scores were similar in both cohorts. Revascularization procedures were done less frequently in GCA than in non‐GCA subjects (19% versus 50%; P = 0.015). Post‐ACS hospital length of stays and complications were similar in both cohorts.ConclusionMultiple cardiovascular risk factors are less atherogenic at incidence of GCA. There is no overall increased risk of ACS in patients with GCA.
Toward a Clinical Definition of Early Osteoarthritis: Onset of Patient‐Reported Knee Pain Begins on Stairs. Data From the Osteoarthritis Initiative
Authors: Hensor Elizabeth M. A. , Dube Bright , Kingsbury Sarah R. , Tennant Alan , Conaghan Philip G. 
Published: July 2014

ObjectiveEarly detection of osteoarthritis (OA) would increase the chances of effective intervention. We aimed to investigate which patient‐reported activity is first associated with knee pain. We hypothesized that pain would occur first during activities requiring weight bearing and knee bending.MethodsData were obtained from the Osteoarthritis Initiative (OAI), a multicenter, longitudinal prospective observational cohort of people who have or are at high risk of OA. Participants completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; Likert scale) annually for up to 7 years. Rasch analysis was used to rank the WOMAC pain questions (activities) in order of affirmation as the pain score increased from 0. For each total WOMAC score category (0–20) we selected 25 individuals at random based on their maximum score across all visits. Fit to the Rasch model was assessed in this subset; stability of question ranking over successive visits was confirmed in the full OAI.ResultsWOMAC data on 4,673 people were included, with 491 selected for subset analysis. The subset data showed good fit to the Rasch model (χ2 = 43.31, P = 0.332). In the full OAI, the “using stairs” question was the first to score points as the total pain score increased from 0 (baseline logit score ± 95% confidence interval −4.74 ± 0.07), then “walking” (−2.94 ± 0.07), “standing” (−2.65 ± 0.07), “lying/sitting” (−2.00 ± 0.08), and finally “in bed” (−1.32 ± 0.09). This ordering was consistent over successive visits.ConclusionKnee pain is most likely to first appear during weight‐bearing activities involving bending of the knee, such as using stairs. First appearance of this symptom may identify a group suitable for early intervention strategies.
Pain, Anxiety, and Negative Outcome Expectations for Activity: Do Negative Psychological Profiles Differ Between the Inactive and Active?
Authors: Gyurcsik Nancy C. , Cary Miranda A. , Sessford James D. , Flora Parminder K. , Brawley Lawrence R. 
Published: July 2014

ObjectiveAdherence to physical activity at ≥150 minutes/week has proven to offer disease management and health‐promoting benefits among adults with arthritis. While highly active people seem undaunted by arthritis pain and are differentiated from the moderately active by adherence‐related psychological factors, knowledge about inactive individuals is lacking. This knowledge may identify what to change in order to help inactive people begin and maintain physical activity. The present study examined the planned, self‐regulated activity of high, moderate, and inactive individuals to determine if differences existed in negative psychological factors.MethodsAdults with a medical diagnosis of arthritis completed online measures of physical activity, perceived pain intensity, pain anxiety, and negative disease‐related outcome expectations from being active. High active (n = 94), moderately active (n = 77), and inactive (n = 104) groups were identified.ResultsA significant multivariate analysis of covariance revealed group differences (P< 0.001). Followup analyses indicated that inactive participants had the most negative psychological profile. Inactive participants reported that negative disease‐related outcomes expectancies were more distressing and likely to occur than either group of active participants and expressed greater pain intensity and pain anxiety than the highly active participants (P< 0.05 for all).ConclusionIdentifying differences in negative psychological factors aids in the understanding of differential adherence between activity groups and highlights possible factors to change in future intervention and research.
Abusive help – helping abuse: The psychodynamic impact of severe personality disorder on caring institutions
Authors: Hinshelwood R.D. 
Published: July 2014

AbstractPersonality‐disordered patients have invariably suffered abuse at the hands of carers when young, and they tend to repeat an abusive relationship when they encounter care in later life. The provision of care in psychiatric, forensic, penal and other institutions may degenerate into a form of unconscious abuse perpetrated against those in care. This is almost always unrecognized and the experience of carers is often to mismanage their own frustrated inability to understand what is happening to them, their charges and the institution.