bluuebunny/crossref_metadata_2025_split huggingface dataset:
L’appropriation d’une innovation thérapeutique dans le cadre d’une maladie chronique : enjeux individuels et organisationnels
Authors: Coutelle-Brillet Patricia , des Garets Véronique , Maubisson Laurent , Rivière Arnaud 
Published: December 2016

Face à l’importance de l’innovation médicale dans la prise en charge des patients et compte tenu des difficultés potentielles d’acceptation des traitements par ces derniers, cet article a pour objectif de mieux comprendre les mécanismes d’adoption d’une innovation thérapeutique par les individus soignés pour une maladie chronique. Dans cette perspective, le cadre théorique de cette recherche est articulé autour des concepts de la Service-Dominant Logic et de l’appropriation développés en marketing. Une étude qualitative, menée auprès de 13 patients d’un service de dialyse, montre que les interviewés ne s’approprient pas un médicament mais plus globalement un service de soins dont ils sont co-créateurs. Par ailleurs, l’étude du processus d’appropriation révèle le rôle de certains « facilitateurs » (tels les guides, les rituels), l’enjeu de la confiance (qui altère les phases d’exploration et de marquage) et l’importance de la phase de nidification. Cette appropriation du service de soins a des implications sur l’autonomie et l’observance des patients, ainsi que sur l’organisation des soins au niveau territorial.
Differing Requirements for MALT1 Function in Peripheral B Cell Survival and Differentiation
Authors: Lee Peishan , Zhu Zilu , Hachmann Janna , Nojima Takuya , Kitamura Daisuke , Salvesen Guy , Rickert Robert C. 
Published: December 2016

Abstract
During a T cell-dependent immune response, formation of the germinal center (GC) is essential for the generation of high-affinity plasma cells and memory B cells. The canonical NF-κB pathway has been implicated in the initiation of GC reaction, and defects in this pathway have been linked to immune deficiencies. The paracaspase MALT1 plays an important role in regulating NF-κB activation upon triggering of Ag receptors. Although previous studies have reported that MALT1 deficiency abrogates the GC response, the relative contribution of B cells and T cells to the defective phenotype remains unclear. We used chimeric mouse models to demonstrate that MALT1 function is required in B cells for GC formation. This role is restricted to BCR signaling where MALT1 is critical for B cell proliferation and survival. Moreover, the proapoptotic signal transmitted in the absence of MALT1 is dominant to the prosurvival effects of T cell-derived stimuli. In addition to GC B cell differentiation, MALT1 is required for plasma cell differentiation, but not mitogenic responses. Lastly, we show that ectopic expression of Bcl-2 can partially rescue the GC phenotype in MALT1-deficient animals by prolonging the lifespan of BCR-activated B cells, but plasma cell differentiation and Ab production remain defective. Thus, our data uncover previously unappreciated aspects of MALT1 function in B cells and highlight its importance in humoral immunity.
Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets
Authors: Patel Vineet I. , Booth J. Leland , Duggan Elizabeth S. , Cate Steven , White Vicky L. , Hutchings David , Kovats Susan , Burian Dennis M. , Dozmorov Mikhail , Metcalf Jordan P. 
Published: December 2016

Abstract
The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage. Six subsets of phagocytic APC (HLA-DR+) were consistently observed. Aside from alveolar macrophages, subsets of Langerin+, BDCA1−CD14+, BDCA1+CD14+, BDCA1+CD14−, and BDCA1−CD14− cells were identified. These subsets varied in their ability to internalize Escherichia coli, Staphylococcus aureus, and Bacillus anthracis particles. All subsets were more efficient at internalizing S. aureus and B. anthracis compared with E. coli. Alveolar macrophages and CD14+ cells were overall more efficient at particle internalization compared with the four other populations. Subsets were further separated into two groups based on their inherent capacities to upregulate surface CD83, CD86, and CCR7 expression levels. Whole-genome transcriptional profiling revealed a clade of “true dendritic cells” consisting of Langerin+, BDCA1+CD14+, and BDCA1+CD14− cells. The dendritic cell clade was distinct from a macrophage/monocyte clade, as supported by higher mRNA expression levels of several dendritic cell–associated genes, including CD1, FLT3, CX3CR1, and CCR6. Each clade, and each member of both clades, was discerned by specific upregulated genes, which can serve as markers for future studies in healthy and diseased states.
NKG2C/E Marks the Unique Cytotoxic CD4 T Cell Subset, ThCTL, Generated by Influenza Infection
Authors: Marshall Nikki B. , Vong Allen M. , Devarajan Priyadharshini , Brauner Matthew D. , Kuang Yi , Nayar Ribhu , Schutten Elizabeth A. , Castonguay Catherine H. , Berg Leslie J. , Nutt Stephen L. , Swain Susan L. 
Published: December 2016

Abstract
CD4 T cells can differentiate into multiple effector subsets, including ThCTL that mediate MHC class II–restricted cytotoxicity. Although CD4 T cell–mediated cytotoxicity has been reported in multiple viral infections, their characteristics and the factors regulating their generation are unclear, in part due to a lack of a signature marker. We show in this article that, in mice, NKG2C/E identifies the ThCTL that develop in the lung during influenza A virus infection. ThCTL express the NKG2X/CD94 complex, in particular the NKG2C/E isoforms. NKG2C/E+ ThCTL are part of the lung CD4 effector population, and they mediate influenza A virus–specific cytotoxic activity. The phenotype of NKG2C/E+ ThCTL indicates they are highly activated effectors expressing high levels of binding to P-selectin, T-bet, and Blimp-1, and that more of them secrete IFN-γ and readily degranulate than non-ThCTL. ThCTL also express more cytotoxicity-associated genes including perforin and granzymes, and fewer genes associated with recirculation and memory. They are found only at the site of infection and not in other peripheral sites. These data suggest ThCTL are marked by the expression of NKG2C/E and represent a unique CD4 effector population specialized for cytotoxicity.
Autophagy in Dendritic Cells and B Cells Is Critical for the Inflammatory State of TLR7-Mediated Autoimmunity
Authors: Weindel Chi G. , Richey Lauren J. , Mehta Abhiruchi J. , Shah Mansi , Huber Brigitte T. 
Published: December 2016

Abstract
Individuals suffering from autoimmune disorders possess a hyperactive cellular phenotype where tolerance to self-antigens is lost. Autophagy has been implicated in both the induction and prevention of autoimmunity, and modulators of this cellular recycling process hold high potential for the treatment of autoimmune diseases. In this study, we determine the effects of a loss of autophagy in dendritic cells (DCs), as well as both B cells and DCs, in a TLR7-mediated model of autoimmunity, similar to systemic lupus erythematosus, where both cell types are critical for disease. Although a loss of DC autophagy slowed disease, the combined loss of autophagy in both cell types resulted in a lethal sepsis-like environment, which included tissue inflammation and hyperproduction of inflammasome-associated cytokines. Ablation of B cell signaling reversed this phenotype, indicating that activation of these cells is an essential step in disease induction. Thus, autophagy plays a dichotomous role in this model of disease.
T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System
Authors: Huang Wei-Chen , Easom Nicholas J. , Tang Xin-Zi , Gill Upkar S. , Singh Harsimran , Robertson Francis , Chang Chiwen , Trowsdale John , Davidson Brian R. , Rosenberg William M. , Fusai Giuseppe , Toubert Antoine , Kennedy Patrick T. , Peppa Dimitra , Maini Mala K. 
Published: December 2016

Abstract
NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)–specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p &lt; 0.001). NKG2DL-expressing T cells were strikingly enriched within HBV-infected livers compared with the periphery or to healthy livers (p &lt; 0.001). NKG2D+NK cells were also increased and preferentially activated in the HBV-infected liver (p &lt; 0.001), in direct proportion to the percentage of MICA/B-expressing CD4 T cells colocated within freshly isolated liver tissue (p &lt; 0.001). This suggests that NKG2DL induced on T cells within a diseased organ can calibrate NKG2D-dependent activation of local NK cells; furthermore, NKG2D blockade could rescue HBV-specific and MICA/B-expressing T cells from HBV-infected livers. To our knowledge, this is the first ex vivo demonstration that non-virally infected human T cells can express NKG2DL, with implications for stress surveillance by the large number of NKG2D-expressing NK cells sequestered in the liver.
Immune Modifications in Fetal Membranes Overlying the Cervix Precede Parturition in Humans
Authors: Marcellin Louis , Schmitz Thomas , Messaoudene Meriem , Chader Driss , Parizot Christophe , Jacques Sébastien , Delaire Jérémy , Gogusev Jean , Schmitt Alain , Lesaffre Corinne , Breuiller-Fouché Michelle , Caignard Anne , Vaiman Daniel , Goffinet François , Cabrol Dominique , Gorochov Guy , Méhats Céline 
Published: December 2016

Abstract
In humans, parturition is currently viewed as an intrauterine outbreak of inflammation, accompanied by a massive release of proinflammatory cytokines at the maternal–fetal interface that comprises the maternal decidua, placenta, and fetal membranes. At term, fetal membranes overlying the cervix, the future site of rupture, show altered morphology and are termed the zone of altered morphology (ZAM). These alterations occur in normal fetal membranes during late pregnancy, in preparation for labor. In this study, transcriptome, flow cytometry, electron microscopy, and immunohistochemistry analyses collectively highlight a local shift in gene expression and lymphocyte activation in the ZAM. Just before labor, we show that highly polymorphic HLA-A, -B, and -C determinants of fetal origin are selectively exposed in the ZAM to the maternal immune system. A graft rejection-like program occurs in the ZAM, which involves 1) the activation of cytotoxic decidual NK cells, and 2) the decline of decidual immunotolerant M2-like macrophages. Comparison with a prior cohort of fetal membranes shows that acute inflammation only takes place after these first steps of immune modifications. Our results therefore strongly argue in favor of local immune remodeling at the onset of parturition.
IL-15 Enables Septic Shock by Maintaining NK Cell Integrity and Function
Authors: Guo Yin , Luan Liming , Patil Naeem K. , Wang Jingbin , Bohannon Julia K. , Rabacal Whitney , Fensterheim Benjamin A. , Hernandez Antonio , Sherwood Edward R. 
Published: December 2016

Abstract
Interleukin 15 is essential for the development and differentiation of NK and memory CD8+ (mCD8+) T cells. Our laboratory previously showed that NK and CD8+ T lymphocytes facilitate the pathobiology of septic shock. However, factors that regulate NK and CD8+ T lymphocyte functions during sepsis are not well characterized. We hypothesized that IL-15 promotes the pathogenesis of sepsis by maintaining NK and mCD8+ T cell integrity. To test our hypothesis, the pathogenesis of sepsis was assessed in IL-15–deficient (IL-15 knockout, KO) mice. IL-15 KO mice showed improved survival, attenuated hypothermia, and less proinflammatory cytokine production during septic shock caused by cecal ligation and puncture or endotoxin-induced shock. Treatment with IL-15 superagonist (IL-15 SA, IL-15/IL-15Rα complex) regenerated NK and mCD8+ T cells and re-established mortality of IL-15 KO mice during septic shock. Preventing NK cell regeneration attenuated the restoration of mortality caused by IL-15 SA. If given immediately prior to septic challenge, IL-15–neutralizing IgG M96 failed to protect against septic shock. However, M96 caused NK cell depletion if given 4 d prior to septic challenge and conferred protection. IL-15 SA treatment amplified endotoxin shock, which was prevented by NK cell or IFN-γ depletion. IL-15 SA treatment also exacerbated septic shock caused by cecal ligation and puncture when given after the onset of sepsis. In conclusion, endogenous IL-15 does not directly augment the pathogenesis of sepsis but enables the development of septic shock by maintaining NK cell numbers and integrity. Exogenous IL-15 exacerbates the severity of sepsis by activating NK cells and facilitating IFN-γ production.
A pediatric echocardiographic Z-score nomogram for a developing country
Authors: Gokhroo Rajendra Kumar , Anantharaj Avinash , Bisht Devendra , Kishor Kamal , Plakkal Nishad , Aghoram Rajeswari , Mondal Nivedita , Pandey Shashi K , Roy Ramsagar 
Published: December 2016

Background:Almost all presently available pediatric echocardiography Z-score nomograms are based on Western data. They may not be a suitable reference standard for assessing the sizes of cardiac structures of children from developing countries.Objective:This study's objective was to collect normative data of 21 commonly measured cardiovascular structures using M-mode and two-dimensional echocardiography in Indian children aged between 4 and 15 years and to derive Z-score nomograms for each.Subjects and Methods:The study was conducted at two centers in India - Ajmer, Rajasthan, and Mohali, Punjab. We studied a community-based sample involving healthy school going children. After excluding children with cardiovascular abnormalities on the screening echocardiogram, 746 children were included in the final analysis. Echocardiographic assessment was performed using a Philips iE33 system.Results and Analysis:For each parameter measured, seven models were evaluated to assess the relationship of that parameter with the body surface area and the one with the best fit was used to plot the Z-score chart for that parameter. Z score charts were thus derived.Conclusions:The Z-score nomograms derived by this study may be better alternatives to the Western nomograms for use in India and other developing countries for preprocedural decision making in the pediatric population. However, they will require validation in large-scale studies before they can become clinically applicable.
Elective nasal continuous positive airway pressure to support respiration after prolonged ventilation in infants after congenital cardiac surgery
Authors: Gandhi Hemang , Mishra Amit , Thosani Rajesh , Acharya Himanshu , Shah Ritesh , Surti Jigar , Sarvaia Alpesh 
Published: December 2016

Background:
We sought to compare the effectiveness of oxygen (O2) treatment administered by an O2 mask and nasal continuous positive airway pressure (NCPAP) in infants after congenital cardiac surgery.

Methods:
In this retrospective observational study, 54 infants undergoing corrective cardiac surgery were enrolled. According to the anesthesiologist's preference, the patients ventilated for more than 48 h were either put on NCPAP or O2 mask immediately after extubation. From pre-extubation to 24 h after treatment, arterial blood gas and hemodynamic data were measured.

Results:
After 24 h of NCPAP institution, the patients showed a significant improvement in oxygenation compared to O2 mask group. Respiratory rate (per minute) decreased from 31.67 ± 4.55 to 24.31 ± 3.69 (P < 0.0001), PO2 (mmHg) increased from 112.12 ± 22.83 to 185.74 ± 14.81 (P < 0.0001), and PCO2 (mmHg) decreased from 42.88 ± 5.01 to 37.00 ± 7.22 (P < 0.0076) in patients on NCPAP. In this group, mean pediatric cardiac surgical Intensive Care Unit (PCSICU) stay was 4.72 ± 1.60 days, with only 2 (11.11%) patients requiring re-intubation.

Conclusion:
NCPAP can be used safely and effectively in infants undergoing congenital cardiac surgery to improve oxygenation/ventilation. It also reduces the work of breathing, PCSICU stay, and may reduce the likelihood of re-intubation.
Elastography in Distinguishing Benign from Malignant Thyroid Nodules
Authors: Colakoglu Bulent , Yildirim Duzgun , Alis Deniz , Ucar Gokhan , Samanci Cesur , Ustabasioglu Fethi Emre , Bakir Alev , Ulusoy Onur Levent 
Published: December 2016

Aim:
The aim of this study is to test the diagnostic success of strain elastography in distinguishing benign from malignant thyroid nodules.

Materials and Methods:
The size, echogenicity, and halo integrity of 293 thyroid nodules and the presence of microcalcification in these nodules were evaluated on gray-scale examination. Doppler characteristics and elastography patterns were also evaluated and recorded. Nodules were classified in four categories (patterns 1–4) based on elastographic examination.

Results:
According to the cytopathological findings, 222 nodules were benign, and 71 nodules were malignant. The risk of a nodule to be malignant was 3.8 times increased by hypoechogenicity, 7.7 times increased by the presence of microcalcification, and 11.5 times increased by the absence of halo. On Doppler patterns, the presence of central vascularity increased the malignancy risk of a nodule by 5.8 times. According to the receiver operating characteristic analysis, patterns 3 and 4 were malignant, and patterns 1 and 2 were benign. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of elastography were 100%, 80.2%, 61.7%, 100%, and 85%, respectively.

Conclusion:
Strain elastography can be used as a noninvasive method in distinguishing benign from malignant thyroid nodules and in identifying the patients who would undergo surgery.
Spinal Realignment for Adult Deformity: Three-column Osteotomies Alter Total Hip Acetabular Component Positioning
Authors: Barry Jeffrey J. , Yucekul Altug , Theologis Alexander A. , Hansen Erik N. , Ames Christopher , Deviren Vedat 
Published: December 2016

Introduction:
A goal of adult spinal deformity surgery is correction of sagittal imbalance by increasing lumbar lordosis (LL), allowing a previously retroverted pelvis to normalize as evidenced by decreases in pelvic tilt (PT). Realignment of pelvic orientation may alter the position of preexisting total hip arthroplasties (THAs).

Methods:
Twenty-seven patients with unilateral THA who underwent thoracolumbar fusions for adult spinal deformity from the pelvis to L1 or above were retrospectively reviewed (levels fused, 10.3 [range, 6 to 17]; age, 70 ± 9 years). Comparisons of preoperative and postoperative spinal deformity parameters, acetabular tilt (AT), and acetabular cup abduction angle (CAA) were performed, with subgroup analysis for those who had undergone three-column osteotomy and those who had not.

Results:
Preoperative deformity was severe, with findings of a sagittal vertical axis >9 cm, PT >25°, and pelvic incidence-LL >20°. Postoperatively, AT decreased significantly (−7° ± 10°; P < 0.001), signifying relative acetabular retroversion. Comparing patients with three-column osteotomy versus those without, AT changes were greater in those with three-column osteotomy (11° ± 7° and −2 ± 10°, respectively; P = 0.024). AT was significantly correlated with changes of PT (r = 0.704; P < 0.001) and LL (r = −0.481; P = 0.011). AT decreased (ie, retroverted) 1° for every 3.23° of LL or 1.13° of PT correction. The coronal plane CAA did not change substantially.

Discussion:
Spinal deformity correction, with techniques such as three-column osteotomy, result in significant THA acetabular component repositioning in the sagittal plane. Resultant decreased AT (ie, retroversion) theoretically may affect tribology, wear, and joint stability and warrants further investigation.
Top 100 Cited Foot and Ankle–Related Articles
Authors: DeHeer Patrick A. , Adams William , Grebenyuk Faye-Rose , Meshulam Eric , Miskin Kory , Koch Tiffany Truong , Groh Corey 
Published: December 2016

Background: Article citations are a well-accepted method of evaluating the influence or impact of a particular article. Other medical specialties have published the top cited articles in their specialty. To date, an analysis of the foot and ankle podiatric medicine–related article citation method has not been published.Methods: Three citation indices were used on October 10, 2014, February 20, 2015, and May 1, 2015, to determine the top 100 cited foot and ankle–related articles.Results: Most of the top 100 cited foot and ankle podiatric medicine–related articles were published in The Journal of Bone and Joint Surgery by medical doctors in the United States in the past two decades, with most of the article topics being the diabetic foot or trauma. The predominant level of evidence for the articles is evenly distributed among levels III, IV, and V.Conclusions: Podiatric medical research and publication has made great strides during the past two decades, particularly in the diabetic foot, but continued research and peer-reviewed journal publication in additional areas regarding the foot and ankle must become a priority in the podiatric medical community.
The Effect of Walking Speed on Foot Kinematics is Modified When Increased Pronation is Induced
Authors: Hornestam Joana F. , Souza Thales R. , Arantes Paula , Ocarino Juliana , Silva Paula L. 
Published: December 2016

Background: The relation between walking speed and foot kinematics during gait is not well established, and neither is it clear whether this relation is modified in the presence of factors expected to increase pronation (eg, abnormal foot alignment). Understanding how foot kinematics is affected by walking speed under varying conditions could contribute to our understanding of stresses to the musculoskeletal system during walking. We evaluated the effect of walking speed on foot kinematics in the frontal plane during gait and determined whether this effect is modified by using medially inclined insoles that force the foot into increased pronation.Methods: Twenty-six healthy young adults were assessed while walking on a treadmill wearing flat insoles and wearing medially inclined insoles. Foot kinematics in the frontal plane was measured with a three-dimensional motion analysis system. Data were analyzed during the stance phase of gait.Results: There was no main effect of speed on average calcaneal position. However, there was a significant insole type × walking speed interaction effect. In the flat insole condition, increased walking speed was associated with a less inverted average calcaneal position (or greater magnitudes of eversion), whereas in the inclined insole condition, higher speeds were associated with a less everted average calcaneal position (or increased magnitudes of inversion).Conclusions: The magnitude of foot eversion increases at faster gait speeds under typical conditions. In the presence of factors that induce excessive pronation, however, this effect is reversed. Results suggest that individuals use greater active control of foot motion at faster speeds in the presence of excessive pronation to improve push-off efficiency. Potential clinical consequences of this functional strategy are discussed.