bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo
Analysis of Infectivity, Fusogenicity, and Incorporation of a Mutagenic Viral Glycoprotein Library Reveals Determinants for Virus Incorporation
Authors: Salamango Daniel J. , Alam Khalid K. , Burke Donald H. , Johnson Marc C. 
Published: May 2016

ABSTRACT

Enveloped viruses utilize transmembrane surface glycoproteins to gain entry into target cells. Glycoproteins from diverse viral families can be incorporated into nonnative viral particles in a process termed pseudotyping; however, the molecular mechanisms governing acquisition of these glycoproteins are poorly understood. For murine leukemia virus envelope (MLV Env) glycoprotein, incorporation into foreign viral particles has been shown to be an active process, but it does not appear to be caused by direct interactions among viral proteins. In this study, we coupled
in vivo
selection systems with Illumina next-generation sequencing (NGS) to test hundreds of thousands of MLV Env mutants for the ability to be enriched in viral particles and to perform other glycoprotein functions. NGS analyses on a subset of these mutants predicted that the residues important for incorporation are in the membrane-proximal external region (MPER), particularly W127 and W137, and the residues in the membrane-spanning domain (MSD) and also immediately flanking it (T140 to L163). These predictions were validated by directly measuring the impact of mutations in these regions on fusogenicity, infectivity, and incorporation. We suggest that these two regions dictate pseudotyping through interactions with specific lipid environments formed during viral assembly.

IMPORTANCE
Researchers from numerous fields routinely exploit the ability to manipulate viral tropism by swapping viral surface proteins. However, this process, termed pseudotyping, is poorly understood at the molecular level. For murine leukemia virus envelope (MLV Env) glycoprotein, incorporation into foreign viral particles is an active process, but it does not appear to occur through direct viral protein-protein interactions. In this study, we tested hundreds of thousands of MLV Env mutants for the ability to be enriched in viral particles as well as perform other glycoprotein functions. Our analyses on a subset of these mutants predict that the glycoprotein regions embedded in and immediately flanking the viral membrane dictate active incorporation into viral particles. We suggest that pseudotyping occurs through specific lipid-protein interactions at the viral assembly site.
Effectiveness of the Baby Friendly Community Initiative in Italy: a non-randomised controlled study
Authors: Cattaneo Adriano , Bettinelli Maria Enrica , Chapin Elise , Macaluso Anna , Córdova do Espírito Santo Lílian , Murante Anna Maria , Montico Marcella 
Published: May 2016

ObjectiveTo assess the effectiveness of the Baby Friendly Community Initiative (BFCI) on exclusive breast feeding at 6 months.DesignControlled, non-randomised trial.Setting18 Local Health Authorities in 9 regions of Italy.Participants5094 mother/infant dyads in 3 cohorts were followed up to 12 months after birth in 3 rounds of data collection: at baseline, after implementation of the intervention in the early intervention group and after implementation in the late intervention group. 689 (14%) dyads did not complete the study.InterventionImplementation of the 7 steps of the BFCI.Main outcome measuresThe rate of exclusive breast feeding at 6 months was the primary outcome; breast feeding at discharge, 3 and 12 months was also measured.ResultsThe crude rates of exclusive breast feeding at discharge, 3 and 6 months, and of any breast feeding at 6 and 12 months increased at each round of data collection after baseline in the early and late intervention groups. At the end of the project, 10% of infants were exclusively breast fed at 6 months and 38% were continuing to breast feed at 12 months. However, the comparison by adjusted rates and logistic regression failed to show statistically significant differences between groups and rounds of data collection in the intention-to-treat analysis, as well as when compliance with the intervention and training coverage was taken into account.ConclusionsThe study failed to demonstrate an effect of the BFCI on the rates of breast feeding. This may be due, among other factors, to the time needed to observe an effect on breast feeding following this complex intervention.
Prevalence, recovery patterns and predictors of quality of life and costs after non-fatal injury: the Brabant Injury Outcome Surveillance (BIOS) study
Authors: de Jongh M A C , Kruithof N , Gosens T , van de Ree C L P , de Munter L , Brouwers L , Polinder S , Lansink K W W ,   BIOS-group
Published: May 2016

IntroductionTrauma is a major public health problem worldwide that leads to high medical and societal costs. Overall, improved understanding of the full spectrum of the societal impact and burden of injury is needed. The main purpose of the Brabant Injury Outcome Surveillance (BIOS) study is to provide insight into prevalence, predictors and recovery patterns of short-term and long-term health-related quality of life (HRQoL) and costs after injury.Materials and methodsThis is a prospective, observational, follow-up cohort study in which HRQoL, psychological, social and functional outcome, and costs after trauma will be assessed during 24 months follow-up within injured patients admitted in 1 of 10 hospitals in the county Noord-Brabant, the Netherlands. Data will be collected by self-reported questionnaires at 1 week (including preinjury assessment), and 1, 3, 6, 12 and 24 months after injury. If patients are not capable of filling out the questionnaires, proxies will be asked to participate. Also, information about mechanism and severity of injury, comorbidity and indirect and direct costs will be collected. Mixed models will be used to examine the course of HRQoL, functional and psychological outcome, costs over time and between different groups, and to identify predictors for poor or good outcome.RelevanceThis study should make a substantial contribution to the international collaborative effort to assess the societal impact and burden of injuries more accurately. The BIOS results will also be used to develop an outcome prediction model for outcome evaluation including, besides the classic fatal, non-fatal outcome.Trial registration numberNCT02508675.
Cost-effectiveness of chiropractic care versus self-management in patients with musculoskeletal chest pain
Authors: Stochkendahl Mette Jensen , Sørensen Jan , Vach Werner , Christensen Henrik Wulff , Høilund-Carlsen Poul Flemming , Hartvigsen Jan 
Published: May 2016

AimsTo assess whether primary sector healthcare in the form of chiropractic care is cost-effective compared with self-management in patients with musculoskeletal chest pain, that is, a subgroup of patients with non-specific chest pain.Methods and results115 adults aged 18–75 years with acute, non-specific chest pain of musculoskeletal origin were recruited from a cardiology department in Denmark. After ruling out acute coronary syndrome and receiving usual care, patients with musculoskeletal chest pain were randomised to 4 weeks of community-based chiropractic care (n=59) or to a single information session aimed at encouraging self-management as complementary to usual care (n=56). Data on resource use were obtained from Danish national registries and valued from a societal perspective. Patient cost and health-related quality-adjusted life years (QALYs; based on EuroQol five-dimension questionnaire (EQ-5D) and Short Form 36-item Health Survey (SF-36)) were compared in cost-effectiveness analyses over 12 months from baseline. Mean costs were €2183 lower for the group with chiropractic care, but not statistically significant (95% CI −4410.5 to 43.0). The incremental cost-effectiveness ratio suggested that chiropractic care was cost-effective with a probability of 97%, given a threshold value of €30 000 per QALY gained. In both groups, there was an increase in the health-related quality of life, and the mean increases were similar over the 12-month evaluation period. The mean differences in QALYs between the groups were negligible.ConclusionsChiropractic care was more cost-effective than self-management. Therefore, chiropractic care can be seen as a good example of a targeted primary care approach for a subgroup of patients with non-specific chest pain.Trial registration numberNCT00462241.
Variabilities in the mortality-related resource utilisation for congenital heart disease
Authors: Danford David A , Karels Quentin , Kutty Shelby 
Published: May 2016

ObjectiveOur objective was to characterise the divergence of effort from outcome in congenital heart disease (CHD) care by measuring mortality-related resource utilisation fraction (MRRUF) for various CHD lesions across institutions of differing volumes.MethodsStudy design was observational analysis of an administrative database, the Pediatric Health Information System (PHIS). The setting was inpatient; 2004–2013. Patients were ≤21 years old with atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy of Fallot (TOF), hypoplastic left heart syndrome (HLHS) or other single ventricle (SV). There were no interventions but diagnosis, institution (and volume), age, length of hospitalisation, billed charges and deaths were recorded. The main outcome measure was MRRUF, the ratio of investments during hospitalisations ending in fatality to investments during all hospitalisations.ResultsThere were 50 939 admissions, 1711 deaths, 703 383 inpatient days, and $10 182 000 000 billed charges. MRRUF varied widely by diagnosis: highest in HLHS (21%), but present in ASD (2%) and VSD (4%). Highest among the very young, MRRUF also increased in HLHS and SV during adolescence. MRRUF increased with hospitalisation duration. MRRUF had no relation to institutional volume, and was static over the decade studied.ConclusionsEven in the modern era we invest heavily in inpatient CHD care that does not produce the desired outcome. Although its magnitude varies by lesion and age, MRRUF is not limited to complex disease in the very young. MRRUF is not decreasing, and is not isolated to high or low volume institutions.
Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem–like Cells
Authors: Giraud Julie , Failla Laura M. , Pascussi Jean-Marc , Lagerqvist Ebba L. , Ollier Jérémy , Finetti Pascal , Bertucci François , Ya Chu , Gasmi Imène , Bourgaux Jean-François , Prudhomme Michel , Mazard Thibault , Ait-Arsa Imade , Houhou Leila , Birnbaum Daniel , Pélegrin André , Vincent Charles , Ryall James G. , Joubert Dominique , Pannequin Julie , Hollande Frédéric 
Published: May 2016

Abstract
Subpopulations of cancer stem–like cells (CSC) are thought to drive tumor progression and posttreatment recurrence in multiple solid tumors. However, the mechanisms that maintain stable proportions of self-renewing CSC within heterogeneous tumors under homeostatic conditions remain poorly understood. Progastrin is a secreted peptide that exhibits tumor-forming potential in colorectal cancer, where it regulates pathways known to modulate colon CSC behaviors. In this study, we investigated the role of progastrin in regulating CSC phenotype in advanced colorectal cancer. Progastrin expression and secretion were highly enriched in colon CSC isolated from human colorectal cancer cell lines and colon tumor biopsies. Progastrin expression promoted CSC self-renewal and survival, whereas its depletion by RNA interference–mediated or antibody-mediated strategies altered the homeostatic proportions of CSC cells within heterogeneous colorectal cancer tumors. Progastrin downregulation also decreased the frequency of ALDHhigh cells, impairing their tumor-initiating potential, and inhibited the high glycolytic activity of ALDHhigh CSC to limit their self-renewal capability. Taken together, our results show how colorectal CSC maintain their tumor-initiating and self-renewal capabilities by secreting progastrin, thereby contributing to the tumor microenvironment to support malignancy. Cancer Res; 76(12); 3618–28. ©2016 AACR.
In SituTumor Vaccination by Combining Local Radiation and Tumor-Specific Antibody or Immunocytokine Treatments
Authors: Morris Zachary S. , Guy Emily I. , Francis David M. , Gressett Monica M. , Werner Lauryn R. , Carmichael Lakeesha L. , Yang Richard K. , Armstrong Eric A. , Huang Shyhmin , Navid Fariba , Gillies Stephen D. , Korman Alan , Hank Jacquelyn A. , Rakhmilevich Alexander L. , Harari Paul M. , Sondel Paul M. 
Published: May 2016

AbstractInterest in combining radiotherapy and immune checkpoint therapy is growing rapidly. In this study, we explored a novel combination of this type to augment antitumor immune responses in preclinical murine models of melanoma, neuroblastoma, and head and neck squamous cell carcinoma. Cooperative effects were observed with local radiotherapy and intratumoral injection of tumor-specific antibodies, arising in part from enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). We could improve this response by combining radiation with intratumoral injection of an IL2-linked tumor-specific antibody (termed here an immunocytokine), resulting in complete regression of established tumors in most animals associated with a tumor-specific memory T-cell response. Given the T-cell response elicited by combined local radiation and intratumoral immunocytokine, we tested the potential benefit of adding this treatment to immune checkpoint blockade. In mice bearing large primary tumors or disseminated metastases, the triple-combination of intratumoral immunocytokine, radiation, and systemic anti–CTLA-4 improved primary tumor response and animal survival compared with combinations of any two of these three interventions. Taken together, our results show how combining radiation and intratumoral immunocytokine in murine tumor models can eradicate large tumors and metastases, eliciting an in situ vaccination effect that can be leveraged further by T-cell checkpoint blockade, with immediate implications for clinical evaluation. Cancer Res; 76(13); 3929–41. ©2016 AACR.
Talimogene Laherparepvec for the Treatment of Advanced Melanoma
Authors: Ott Patrick A. , Hodi F. Stephen 
Published: May 2016

Abstract
Talimogene laherparepvec (T-VEC) is a first-in-class oncolytic virus that mediates local and systemic antitumor activity by direct cancer cell lysis and an “in situ vaccine” effect. Based on an increased durable response rate compared with granulocyte macrophage–colony stimulating factor in a randomized phase III trial, it was approved by the FDA for the treatment of melanoma metastatic to skin or lymph nodes. The drug is currently in clinical trials as monotherapy and in combination with immune-checkpoint inhibitors and radiotherapy in melanoma and other cancers. The mechanism of action, toxicity, and efficacy as well as its role in current clinical practice and potential future applications are reviewed. Clin Cancer Res; 22(13); 3127–31. ©2016 AACR.
Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
Authors: Xu Ran , Shimizu Fumiko , Hovinga Koos , Beal Kathryn , Karimi Sasan , Droms Leif , Peck Kyung K. , Gutin Philip , Iorgulescu J. Bryan , Kaley Thomas , DeAngelis Lisa , Pentsova Elena , Nolan Craig , Grommes Christian , Chan Timothy , Bobrow Dylan , Hormigo Adilia , Cross Justin R. , Wu Nian , Takebe Naoko , Panageas Katherine , Ivy Percy , Supko Jeffrey G. , Tabar Viviane , Omuro Antonio 
Published: May 2016

Abstract
Purpose: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role.
Experimental Design: In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood–brain barrier disruption. Finally, recurrent tumors were also sampled and assessed for Notch pathway responses while on treatment.
Results: Treatment was well tolerated and no dose-limiting toxicities were observed. IHC of treated tumors showed a significant decrease in proliferation and in the expression of the Notch intracellular domain (NICD) by tumor cells and blood vessels. Patient-specific organotypic tumor explants cultures revealed a specific decrease in the CD133+ CIS population upon treatment. Perfusion MRI demonstrated a significant decrease in relative plasma volume after drug exposure. Gene expression data in recurrent tumors suggested low Notch signaling activity, the upregulation of key mesenchymal genes, and an increase in VEGF-dependent angiogenic factors.
Conclusions: The addition of RO4929097 to temozolomide and radiotherapy was well tolerated; the drug has a variable blood–brain barrier penetration. Evidence of target modulation was observed, but recurrence occurred, associated with alterations in angiogenesis signaling pathways. Clin Cancer Res; 22(19); 4786–96. ©2016 AACR.
РЕЗУЛЬТАТИ ЗОВНІШНЬОГО І ВНУТРІШНЬОГО МОНІТОРИНГУ ЯКОСТІ ВИЩОЇ ОСВІТИ У ВДНЗУ “УКРАЇНСЬКА МЕДИЧНА СТОМАТОЛОГІЧНА АКАДЕМІЯ” ЗА 2015 КАЛЕНДАРНИЙ РІК
Authors: Zhdan V. M. , Bobyriov V. M. , Bilash S. M. , Bieliaieva O. M. 
Published: May 2016

<p class="1reziume">Стаття присвячена актуальному нині питанню моніторингу якості освіти. Проаналізовано результати зовнішнього і внутрішнього моніторингу якості вищої освіти у ВДНЗУ “Українська медична стоматологічна академія” за 2015 календарний рік. Показано, що внутрішній моніторинг у вигляді самоаналізу і самооцінювання – це вимога часу та об’єктивна потреба інноваційного розвитку освітньої діяльності навчального закладу. У висновках зазначається, що внутрішній моніторинг дає змогу простежувати динаміку процесуального і результативного аспектів якості навчання, забезпечує умови для підвищення ефективності управління якістю освітнього процесу, підвищує відповідальність усіх суб’єктів (студентів, науково-педагогічних працівників, адміністрації, навчально-допоміжного персоналу), обумовлює внесення необхідних коректив в освітній процес, слугує міцним поштовхом для розвитку культури університетської автономії. </p>
Quantitative Analysis of the Isolation Area During the Chronic Phase After a 28-mm Second-Generation Cryoballoon Ablation Demarcated by High-Resolution Electroanatomic Mapping
Authors: Miyazaki Shinsuke , Taniguchi Hiroshi , Hachiya Hitoshi , Nakamura Hiroaki , Takagi Takamitsu , Iwasawa Jin , Hirao Kenzo , Iesaka Yoshito 
Published: May 2016

Background—
The post–second-generation cryoballoon (CB) ablation isolation area during the chronic phase has not been described. The aim of this study was to quantitatively evaluate the chronic-phase isolation area after 28-mm second-generation CB ablation and compare it to the estimated conventional radiofrequency circumferential pulmonary vein isolation (CPVI) line.

Methods and Results—

Thirty-two patients with paroxysmal atrial fibrillation underwent pulmonary vein (PV) isolation using second-generation CB. After a median of 6.0 (4.0–9.0) months, the PV isolation area was evaluated using high-resolution mapping (1-mm electrode, 2-mm interelectrode spacing; 527±99 points per map) and pacing techniques in all patients (17 with and 15 without arrhythmia recurrence beyond blanking period) and compared with estimated conventional radiofrequency CPVI area. PV reconnections were observed in 34 of 126 PVs (27.0%) among 21 of 32 patients (65.6%), which were eliminated by a median of 1.0 (1.0–3.0) focal radiofrequency application. The left- and right-sided PV antrum isolation area and nonablated posterior wall areas were 9.8±1.7, 8.1±2.3, and 17.0±6.1 cm
2
, respectively. The cryoablated areas were significantly smaller than the estimated conventional radiofrequency CPVI areas in all but the right inferior PV. The difference was highest in the left superior PV. In 2 patients (6.3%), recurrent atrial fibrillation originated from the foci identified at the left superior PV antrum outside the CB isolation area but inside the estimated conventional radiofrequency CPVI line.

Conclusions—
Although the PV isolation areas during the chronic phase after the second-generation CB ablation were generally wide, they were significantly smaller than the area encircled by the CPVI line except at the right inferior PV antrum. Recurrent atrial fibrillation could originate from the left superior PV antrum and could be isolated by a CPVI but not by a CB.
Mortality Among Patients Hospitalized With Heart Failure and Diabetes Mellitus
Authors: Win Theingi Tiffany , Davis Herbert T. , Laskey Warren K. 
Published: May 2016

Background—
Case fatality and hospitalization rates for US patients with heart failure (HF) have steadily decreased during the past several decades. Diabetes mellitus (DM), a risk factor for, and frequent coexisting condition with, HF continues to increase in the general population.

Methods and Results—

We used the National Inpatient Sample to estimate overall as well as age-, sex-, and race/ethnicity-specific trends in HF hospitalizations, DM prevalence, and in-hospital mortality among 2.5 million discharge records from 2000 to 2010 with HF as primary discharge diagnosis. Multivariable logistic and Poisson regression were used to assess the impact of the above demographic characteristics on in-hospital mortality. Age-standardized hospitalizations decreased significantly in HF overall and in HF with DM. Age-standardized in-hospital mortality with HF declined from 2000 to 2010 (4.57% to 3.09%,
P
trend
<0.0001), whereas DM prevalence in HF increased (38.9% to 41.9%,
P
trend
<0.0001) as did comorbidity burden. Age-standardized in-hospital mortality in HF with DM also decreased significantly (3.53% to 2.27%,
P
trend
<0.0001). After adjusting for year, age, and comorbid burden, males remained at 17% increased risk versus females, non-Hispanics remained at 12% increased risk versus Hispanics, and whites had a 30% higher mortality versus non-white minorities. Absolute mortality rates were lower in younger versus older patients, although the rate of decline was attenuated in younger patients.

Conclusions—
In-hospital mortality in HF patients with DM significantly decreased during the past decade, despite increases in DM prevalence and comorbid conditions. Mortality rate decreases among younger patients were significantly attenuated, and mortality disparities remain among important demographic subgroups.
Michio Yanai and Tropical Waves
Authors: Takayabu Yukari N. , Kiladis George N. , Magaña Victor 
Published: May 2016

Abstract
Insights by Professor Michio Yanai on tropical waves, which have been vital ingredients for progress in tropical meteorology over the last half-century, are recollected. This study revisits various aspects of research on tropical waves over the last five decades to examine, in Yanai’s words, “the nature of ‘A-scale’ tropical wave disturbances and the interaction of the waves and the ‘B-scale’ phenomena (cloud clusters),” the fundamental problem posed by Yanai at the design phase of the GARP Atlantic Tropical Experiment (GATE) in 1971. The various contributions of Michio Yanai to the current understanding of the dynamics of the tropical atmosphere are briefly reviewed to show how his work has led to several current theories in this field.