bluuebunny/crossref_metadata_2025 huggingface dataset:
Biology and development of galls induced by Lopesia sp. (Diptera: Cecidomyiidae) on leaves of Mimosa gemmulata (Leguminosae: Caesalpinioideae)
Authors: Costa Elaine Cotrim , Carneiro Renê Gonçalves da Silva , Silva Juliana Santos , Isaias Rosy Mary dos Santos
Published: April 2018

Analyses of gall biology and development allow determination of morphogenesis events in host-plant organs that are altered by galling insects. Currently, we assume that there is a correlation between Lopesia sp. instars and the alterations in gall tissues on Mimosa gemmulata that generate the gall shape. The development of Lopesia sp. (three larval instars, pupae and adult) correlates positively with gall growth, especially on the anticlinal axis. First-instar larvae are found in galls at the stage of induction, Instar 2 in galls at early growth and development, Instar 3 in galls at late growth and development, pupae in galls at maturation, and the adult emerges from senescent galls. At induction, the larva stimulates cell differentiation in pinnula and pinna-rachis tissues on M. gemmulata. At early growth and development stages, cell division and expansion are increased, and non-glandular trichomes assist gall closing. Homogenous parenchyma and neoformed vascular bundles characterise late growth and development. At maturation, tissues are compartmentalised and cells achieve major expansion through elongation. At senescence, galls open by the falling of trichomes, and mechanical and nutritive cells have thickened walls. The neoformed nutritive tissue nurtures the developing Lopesia sp., whose feeding behaviour influences the direction of cell elongation, predominantly periclinal, determinant for gall bivalve shape.
The plant hormone ethylene restricts
Arabidopsis
growth via the epidermis
Authors: Vaseva Irina Ivanova , Qudeimat Enas , Potuschak Thomas , Du Yunlong , Genschik Pascal , Vandenbussche Filip , Van Der Straeten Dominique
Published: April 2018

Significance

Ethylene is a gaseous hormone that controls plant life throughout development. Being a simple hydrophobic molecule, it can freely enter cells; therefore, the cell type specificity of its action is challenging. By means of tissue-specific expression of two negative regulators of the signaling cascade, we selectively disrupted the ethylene signal in different cell types without affecting its biosynthesis. We demonstrate that ethylene restricts plant growth by dampening the effect of auxins in the outermost cell layer. We further show that this epidermis-specific signaling has an impact on the growth of neighboring cells, suggesting that the master controller of cell expansion resides in the epidermis, where it senses the environment and, subsequently drives growth, of the inner tissues.
Assessing historical literacy among 12‐year‐old Finns
Authors: Rantala Jukka , Khawaja Amna
Published: April 2018

The new national core curriculum has been put into operation in Finland. Teaching and learning is intended to focus on historical literacy. In this paper, we study how it can be assessed with a pen‐and‐paper test, and what that reveals in regards to the mastering of historical literacy among elementary pupils. To study this, we designed a test where pupils analysed sources, answered open‐ended questions, and filled out weighted multiple‐choice questions. Furthermore, we implemented the test with the think‐aloud method. The results from this indicate the way 12‐year‐olds read historical documents and formulate their own interpretations. The results demonstrate that most of the pupils succeeded in acquiring historical information from different sources, as well as understanding the interpretative nature of historical knowledge. The test also revealed that pupils can identify some intentions of the sources’ producers, as well as reasoning through their own interpretations using a single source. Some pupils, however, could not process the cognitive noise inherent to the test (i.e. conflicting sources). Some of them also considered an authoritative source to be principally more reliable than other sources. Our study sheds light on which kind of task can be used at the elementary level to assess historical literacy.
SFT-4/Surf4 control ER export of soluble cargo proteins and participate in ER exit site organization
Authors: Saegusa Keiko , Sato Miyuki , Morooka Nobukatsu , Hara Taichi , Sato Ken
Published: April 2018

Lipoproteins regulate the overall lipid homeostasis in animals. However, the molecular mechanisms underlying lipoprotein trafficking remain poorly understood. Here, we show that SFT-4, a Caenorhabditis elegans homologue of the yeast Erv29p, is essential for the endoplasmic reticulum (ER) export of the yolk protein VIT-2, which is synthesized as a lipoprotein complex. SFT-4 loss strongly inhibits the ER exit of yolk proteins and certain soluble cargo proteins in intestinal cells. SFT-4 predominantly localizes at ER exit sites (ERES) and physically interacts with VIT-2 in vivo, which suggests that SFT-4 promotes the ER export of soluble proteins as a cargo receptor. Notably, Surf4, a mammalian SFT-4 homologue, physically interacts with apolipoprotein B, a very-low-density lipoprotein core protein, and its loss causes ER accumulation of apolipoprotein B in human hepatic HepG2 cells. Interestingly, loss of SFT-4 and Surf4 reduced the number of COPII-positive ERES. Thus, SFT-4 and Surf4 regulate the export of soluble proteins, including lipoproteins, from the ER and participate in ERES organization in animals.
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia
Authors: Cronk James C. , Filiano Anthony J. , Louveau Antoine , Marin Ioana , Marsh Rachel , Ji Emily , Goldman Dylan H. , Smirnov Igor , Geraci Nicholas , Acton Scott , Overall Christopher C. , Kipnis Jonathan
Published: April 2018

Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.
Discussion about effecting of stiffener in four bolts in a row end plate connection for long span and heavy load steel structures in Vietnam
Authors: Huong Khang T , Nguyen Cung H
Published: April 2018

Nowadays, steel structure industry in Vietnam is in strong development. The construction of steel structure becomes larger span and heavier load. The issue spawned a number of issues arise from optimizing connections. Typical of steel connections in prefabricated steel structure that is an end plate (face plate) bolted connection. When the connection carried a heavy load, then the number of bolts is required much more. Increasing the number of rows bolts will less effective because can still not enough strength requirements, the bolts in row near rotational center will level arm reduction, then it cannot carry heavy loads. The current solution is doing multiple bolts in a row. Current standards such as EN [1], AISC [2] are no specific guidelines for calculating the connection four bolts in a row that primarily assumes the way works like a T-stub of the two bolts a row. Some articles studied T-stub four bolts in a row [3], [4], [5], [6] by component method but it has some components which weren’t considered. In this paper, in order to provide a contribution to improve the T-stub four bolts in a row, the stiffener component in T-stub will be added and compared with T-stub without stiffener by the finite element model to demonstrate effectiveness in reducing stress and displacement of T-stub. It gives ideas for the economic design of four bolts in a row end plate connection in Vietnam for future.
The effect of crack width on the service life of reinforced concrete structures
Authors: Van Hung Nguyen , Hung Vu Viet , Viet Tran Bao
Published: April 2018

Reinforced concrete has become a widely used construction material around the world. Nowadays, the assessment of deterioration and life expectancy of reinforced concrete structure is very important and necessary as concrete is a complex material with brittle failure. Under the effect of load and over time, cracks occur in the structure, significantly reducing its performance and durability. Therefore, a number of models for predicting the penetration of chloride ions into the concrete were proposed to assess the durability of the structure. In the study performed by T B Viet (2016) [1], the author proposed a new theoretical model, especially considering the effects of macro and micro cracking on the diffusion coefficient of chloride ion in the cracked concrete. The following experimental results, in term of electrical indication of concrete’s ability to resist chloride ion penetration, are used to calculate the lifespan of a reinforced concrete structure according to Dura Crete approach [8] with different crack widths to evaluate the accuracy and reliability of the above model in the range of concrete compressive strength of 30-70MPa.
Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Child Enteric Protozoan Infections in Rural Bangladesh: A Cluster-Randomized Controlled Trial
Authors: Lin Audrie , Ercumen Ayse , Benjamin-Chung Jade , Arnold Benjamin F , Das Shimul , Haque Rashidul , Ashraf Sania , Parvez Sarker M , Unicomb Leanne , Rahman Mahbubur , Hubbard Alan E , Stewart Christine P , Colford John M , Luby Stephen P
Published: April 2018

Background

We evaluated effects of individual and combined water, sanitation, handwashing (WSH), and nutritional interventions on protozoan infections in children.

Methods

We randomized geographical clusters of pregnant women in rural Bangladesh into chlorinated drinking water, hygienic sanitation, handwashing, nutrition, combined WSH, nutrition plus WSH (N+WSH), or control arms. Participants were not masked. After approximately 2.5 years of intervention, we measured Giardia, Cryptosporidium, and Entamoeba histolytica prevalence and infection intensity by multiplex real-time polymerase chain reaction of child stool. Analysis was intention-to-treat.

Results

Between May 2012 and July 2013, we randomized 5551 pregnant women. At follow-up, among 4102 available women, we enrolled 6694 children into the protozoan assessment. We analyzed stool from 5933 children (aged ~31 months) for protozoan infections. Compared with 35.5% prevalence among controls, Giardia infection prevalence was lower in the sanitation (26.5%; prevalence ratio [PR], 0.75 [95% confidence interval {CI}, .64–.88]), handwashing (28.2%; PR, 0.80 [95% CI, .66–.96]), WSH (29.7%; PR, 0.83 [95% CI, .72–.96]), and N+WSH (26.7%; PR, 0.75 [95% CI, .64–.88]) arms. Water and nutrition interventions had no effect. Low prevalence of E. histolytica and Cryptosporidium (<2%) resulted in imprecise effect estimates.

Conclusions

Individual handwashing and hygienic sanitation interventions significantly reduced childhood Giardia infections, and there were no effects of chlorinated drinking water and nutrition improvements in this context. Combined WSH interventions provided no additional benefit. To reduce Giardia infection, individual WSH interventions may be more feasible and cost-effective than combined interventions in similar rural, low-income settings.

Clinical Trials Registration

NCT01590095.
bpRNA: large-scale automated annotation and analysis of RNA secondary structure
Authors: Danaee Padideh , Rouches Mason , Wiley Michelle , Deng Dezhong , Huang Liang , Hendrix David
Published: April 2018

While RNA secondary structure prediction from sequence data has made remarkable progress, there is a need for improved strategies for annotating the features of RNA secondary structures. Here, we present bpRNA, a novel annotation tool capable of parsing RNA structures, including complex pseudoknot-containing RNAs, to yield an objective, precise, compact, unambiguous, easily-interpretable description of all loops, stems, and pseudoknots, along with the positions, sequence, and flanking base pairs of each such structural feature. We also introduce several new informative representations of RNA structure types to improve structure visualization and interpretation. We have further used bpRNA to generate a web-accessible meta-database, ‘bpRNA-1m’, of over 100 000 single-molecule, known secondary structures; this is both more fully and accurately annotated and over 20-times larger than existing databases. We use a subset of the database with highly similar (≥90% identical) sequences filtered out to report on statistical trends in sequence, flanking base pairs, and length. Both the bpRNA method and the bpRNA-1m database will be valuable resources both for specific analysis of individual RNA molecules and large-scale analyses such as are useful for updating RNA energy parameters for computational thermodynamic predictions, improving machine learning models for structure prediction, and for benchmarking structure-prediction algorithms.
Differences in Pressure Within the Sac of Human Ruptured and Nonruptured Cerebral Aneurysms
Authors: Li Yiping , Corriveau Mark , Aagaard-Kienitz Beverly , Ahmed Azam , Niemann David
Published: April 2018

BACKGROUND

Hemodynamics plays a critical role in the development, growth, and rupture of intracranial aneurysms. This data could be vital in determining individual aneurysm rupture risk and could facilitate our understanding of aneurysms.

OBJECTIVE

To present the largest prospective cross-sectional cohort study of intrasaccular pressure recordings of ruptured and nonruptured intracranial aneurysms and describe the hemodynamic differences that exist between ruptured and nonruptured aneurysms.

METHODS

During endovascular treatment, a standard 1.8-Fr 200 m length microcatheter was navigated into the dome of the aneurysm prior to coil embolization. With the microcatheter centralized within the dome of the aneurysm, an arterial pressure transducer was attached to the proximal end of the microcatheter to measure the stump pressure inside the aneurysm dome.

RESULTS

In 68 aneurysms (28 ruptured, 40 nonruptured), we observed that ruptured cerebral aneurysms had a lower systolic and mean arterial pressure compared to nonruptured cohort (P = .0008). Additionally, the pulse pressures within the dome of ruptured aneurysms were significantly more narrow than that of unruptured aneurysms (P = .0001). These findings suggest that there may be an inherent difference between ruptured and nonruptured aneurysms and such recordings obtained during routine digital subtraction angiography could potentially become a widely applied technique to augment risk stratification of aneurysms.

CONCLUSION

Our preliminary data present new evidence distinguishing ruptured from unruptured aneurysms that may have a critical role as a predictive parameter to stratify the natural history of nonruptured intracranial aneurysms and as a new avenue for future investigation.
Are Fetal-Type Posterior Cerebral Arteries Associated With an Increased Risk of Posterior Communicating Artery Aneurysms?
Authors: Thiarawat Peeraphong , Jahromi Behnam Rezai , Kozyrev Danil A , Intarakhao Patcharin , Teo Mario K , Choque-Velasquez Joham , Niemelä Mika , Hernesniemi Juha
Published: April 2018

BACKGROUND

Fetal-type posterior cerebral arteries (F-PCAs) might result in alterations in hemodynamic flow patterns and may predispose an individual to an increased risk of posterior communicating artery aneurysms (PCoAAs).

OBJECTIVE

To determine the association between PCoAAs and the presence of ipsilateral F-PCAs.

METHODS

We retrospectively reviewed the radiographic findings from 185 patients harboring 199 PCoAAs that were treated at our institution between 2005 and 2015. Our study population consisted of 4 cohorts: (A) patients with 171 internal carotid arteries (ICAs) harboring unilateral PCoAAs; (B) 171 unaffected ICAs in the same patients from the first group; (C) 28 ICAs of 14 patients with bilateral PCoAAs; and (D) 180 ICAs of 90 patients with aneurysms in other locations. We then determined the presence of ipsilateral F-PCAs and recorded all aneurysm characteristics.

RESULTS

Group A had the highest prevalence of F-PCAs (42%) compared to 19% in group B, 3% in group C, and 14% in group D (odds ratio A : B = 3.041; A : C = 19.626; and A : D = 4.308; P < .001). PCoAAs were associated with larger diameters of the posterior communicating arteries (median value 1.05 vs 0.86 mm; P = .001). The presence of F-PCAs was associated with larger sizes of the aneurysm necks (median value 3.3 vs 3.0 mm; P = .02).

CONCLUSION

PCoAAs were associated with a higher prevalence of ipsilateral F-PCAs. This variant was associated with larger sizes of the aneurysm necks but was not associated with the sizes of the aneurysm domes or with their rupture statuses.
P-A7 HIV disease history in perinatally HIV infected adolescents with interrupted care
Authors: Evans-Gilbert Tracy , Ann Williams Shelly , Reid Gail , Christie Celia
Published: April 2018

Early initiation of HAART preserves the robust immune system of perinatally HIV infected children and limits viral reservoir size. Our aim was to study the current immune and virological status of perinatally infected adolescents who returned after defaulting care. A retrospective analysis was conducted on laboratory outcomes stratified by defaulters and non-defaulters and among age bands at HAART commencement. Among 78 patients, the median age was 14 years [IQR 13,17]. HAART was commenced at a median age of 6 years [IQR 3,8] with 45 (57%) at >6 years. Among 27 defaulters the median time of default was 22 months. Total time on HAART was a mean of 8.5 years ± 3 years and 56 (71%) were on protease inhibitors. Zenith HIV RNA load was a median of 4.8 log10 copies/ml [IQR 4.2–5.2]. Nadir CD4 cell count was 368 [IQR 61,648]. Median current CD4 percent was 33.5% [IQR 18,46] Duration of CD4 of 15-25% was 12 months [IQR 4, 32] for defaulters compared with 4 months [IQR 0,8] for non-defaulters. The mean duration of viral load <500 copies/mL was 1.48 ± 1.68 years among defaulters, 3.6± 3.2 years among non defaulters (p < 0.0001); 3.9 ± 3 for those commencing HAART at age 1-5 years, and 2.4 ± 2.6 for >6 years (p < 0.05). Seventy percent of adolescents commencing HAART at 1-5 years versus 43% at age >6 year had a current CD4 count >500 (P < 0.03). Virologic suppression was 67% in the 1–5 year band versus 27% in the >6 year band (p < 0.0001). Defaulters and non defaulters did not differ with current virologic or immunologic markers. Late age at starting HAART had a greater negative influence on final outcome than interrupted therapy. These results suggest the potential in HIV remission research of interrupting HAART after early initiation of treatment.
P-A8 Establishing tissue reservoirs for the human immunodeficiency virus in humanized mice
Authors: Su Hang , Dash Prasanta , Gorantla Santhi , Poluektova Larisa , Gendelman Howard
Published: April 2018

Due to extraordinary challenges of early viral detection and restricted access to anatomical sites, it remains imperative to track early temporal dynamics of viral latency establishment. The development of humanized mice has provided new insights into the immunology, pathogenesis, treatment, prevention, and measured eradication. In the current study, we applied 2 widely used humanized mouse models of HIV/AIDS; human CD34+ hematopoietic stem cells (HSC) and peripheral blood lymphocytes (hu-PBLs)-transplanted NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice, to investigate early events in HIV latency. Twenty hu-HSC or hu-PBLs mice were injected intraperitoneally with HIV-1 ADA at 104 TCID50. Infected animals were randomly separated into 4 groups and sacrificed at day 3, 5, 7 and 14 after infection. Blood and tissues were harvested for immunohistochemistry and semi-nested PCR tests for HIV-1 DNA and RNA. Peripheral CD4+ T cells were reduced by around 10% after HIV-1 infection in hu-HSCs mice but over 20% in hu-PBLs mice. IHC tests showed HIV-1p24 expressing cells only in 14-day infected hu-HSCs mice but in all infected hu-PBLs mice. HIV-1 RNA and DNA were observed in 14-day infected hu-HSCs mice from spleen lung liver and gut at 106-8 copies/106 hCD45+ cells, whereas detected in 2/5 animals (∼106 copies) at early time points. They were observed in all infected hu-PBLs mouse tissues (∼106copies/106 hCD45+ cells in 3-day group and 106-8 copies in other time points). HIV-1 was detected both hu-HSCs and hu-PBLs models as early as 3 days after infection but more robust within the latter. This may be related to various host restriction factors. Targeting these host factors may provide stronger clues about establishment of HIV persistence.
P-E3 Assessment of internationally-available HIV test kits for their suitability to meet manufacturers' claims
Authors: Constantine Niel , Abouhamda Ahmed , Athwal Bhavneet , Saleh Ahmed , Paulus Samantha
Published: April 2018

Background:

HIV test kits, particularly rapid HIV tests, are used throughout the world as a primary measure to protect the blood supply and provide diagnosis to save lives. The US government purchases large numbers of HIV tests at considerable expense, and expects them to perform adequately.

Objective:

To assess a large number and variety of HIV test kits to determine if they meet the claims of the manufacturers.

Methods:

From September 2010 through July 2017, a total of 1,123 lots of HIV test kits from 14 manufacturers and representing 11 different tests from 26 countries, were received for evaluation at the INSTITUTE OF HUMAN VIROLOGY. Each test kit was assessed for performance characteristics using panels of sera (n=30 or 160) that included positives for HIV-1 and HIV-2 (n=8 or 80), and negatives (n=22 or 80). Several HIV-1 positive samples were weak positives derived from seroconversion panels (SeraCare). Test kits were also assessed for precision using several HIV-1 weak positive samples tested in replicate.

Results:

Of the HIV test kit lots evaluated, 99.2% successfully passed the evaluation with perfect performance. Of the 9 lots that did not pass, 3 were found to produce high background that interfered with reading, 2 performed inadequately with high-temperature testing, and 4 exhibited greater than one false-positive result. In one assessment, a country had reported poor performance of a test kit, but the test kit passed the evaluation; this resulted in a visit to the country to assess the laboratory's activities.

Conclusion:

In our evaluation of a large number and variety of HIV test kit lots from 14 manufacturers, nearly all performed as expected and met the manufacturers' claims.
P-G2 Development of engineered T-cell immmunotherapy for treating Adult-T cell leukemia caused by HTLV-1
Authors: Zapata Juan , Tagaya Yutaka
Published: April 2018

HTLV-1 is perhaps the most oncogenic virus in humans. Five percent to ten percent of individuals infected by HTLV-1 develop a fatal T-cell leukemia (ATL) after 2-3 decades of latency. Conventional chemotherapy only creates escape mutants in ATL. Novel treatments including retroviral drugs, Arsenic Trioxide/IFNa combination, or Allogeneic stem cell transplant have increased the 5-year survival, but there is still need to establish a cure. We chose an immunotherapy approach because all leukemic cells express some HTLV-1 viral proteins allowing to distinguish normal and HTLV-1 infected cells by the host immune system. In addition, anti-HTLV-1 immunity is suppressed in ATL patients. We aim to target HBZ (an antisense protein of HTLV-1) for this purpose because; 1) the frequency of T cells recognizing HBZ correlates well with low HTLV-1 proviral loads in contrast to T cells against Tax-1 or Env. 2) Unlike Tax-1, HBZ is constantly expressed by all stages of ATL cells. The challenge is that HBZ is an extremely weak immunogen. We identified a few epitopes of HBZ that stably find to class I HLA molecules. We tested them using an in vivo model of ATL in humanized mice. Immunization by HBZ showed little therapeutic effects in these mice. DC immunization showed prolonged survival, but did not protect mice from ATL. Thus, we grew anti-HBZ CD8 T cells by immunizing normal T cells ex vivo, enriched them by HBZ-tetramer sorting. T-cell therapy involving anti-HBZ CD8 T cells successfully protected host mice, prompting us to rely on an “engineered T cell” strategy as novel treatment of acute/lymphomatous ATL cases.
B-103 Fc Bridged Cellular Cytotoxicity (FcBCC): A novel mechanism by which NK cells recognize HSV
Authors: Dai Hongsheng , Caligiuri Michael A.
Published: April 2018

The initial infection by herpes simplex virus 1 (HSV1) is usually a self-limited event, but the mechanism of this protection prior to the development of a primary humoral response is unknown. Individuals deficient in natural killer (NK) cells can suffer from overwhelming and at times fatal HSV1 infection. The NK cell surface is naturally coated with IgG that is bound to Fcγ receptor CD16a. Here we show that human NK cells utilize the Fc portion of IgG bound to its cell surface to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc portion of IgG but at a site distinct from that of CD16a. The Fc-bridge formed between the HSV1-infected cell and the NK cell results in NK cell activation and spontaneous lysis of the HSV-infected cell in the absence of HSV-specific antibody. In vivo, the absence of the Fc portion of human IgG, or of NK cells, results in death from primary HSV1 infection. This mechanism, which we call Fc bridged cellular cytotoxicity (FcBCC) may be broadly applicable to Fcγ receptor-bearing immune cells and other pathogens encoding Fc-binding proteins.
B-105 Discovery to first-in-man studies of a multi-peptide-based hepatocellular carcinoma vaccine - HEPAVAC
Authors: Buonaguro Luigi
Published: April 2018

Hepatocellular (HCC)/normal adjacent tissue matched samples have been collected for HLA immunopeptidome analysis. 17 HCC samples from HLA-A*02+ patients and 15 samples from HLA-A*24+ patients have been analysed by mass spectrometry. RNA-expression profiles have been established for 12 HCC samples. HLA-presentation/expression of peptides on primary HCC samples (as well as mRNA expression) were compared to normal tissue samples from relevant organs (including heart, brain, lung, kidney, liver, nerve, skin etc.) present in the Immatics' database.

A total of 16 peptides have been selected and confirmed for immunogenicity for the HepaVac vaccine and are currently synthesized according to GMP standard. Of these, 7 are restricted to HLA-A*02; 5 to HLA-A*24 and 4 to HLA class II.

A single-arm, first-in-man trial entitled HepaVac-101 is designed to investigate in patients with very early, early and intermediate stage of HCC the off-the-shelf multi-peptide-based HCC vaccine (IMA970) plus the CV8102 adjuvant (RNAdjuvant®) following a single pre-vaccination infusion of low-dose cyclophosphamide acting as an immunomodulator. The study drugs are applied without concomitant anti-tumor therapy with the intention to reduce risk of tumor recurrence/progression in patients who have received all indicated standard treatments. The primary endpoints are safety, tolerability, and immunogenicity. Secondary/exploratory endpoints are additional immunological parameters in blood (eg, regulatory T-cells, myeloid-derived suppressor cells, impact of the standard therapy on the natural immune response), infiltrating T-lymphocytes in tumor tissue, biomarkers in blood and tissue, disease-free survival/progression-free survival and overall survival.
Illuminating Graduate Medical Education Outcomes in Order to Improve Them
Authors: Weinstein Debra F. , Thibault George E.
Published: April 2018

Optimizing clinician education is an essential step toward enhancing health outcomes, and graduate medical education (GME)—as the pipeline for producing the nation’s physicians—is an appropriate target for improvement. This Invited Commentary focuses on the need to clarify the specific goals of GME and measure achievement of those goals, using consistent metrics. The authors report on an October 2017 National Academies of Sciences, Engineering, and Medicine (NASEM) workshop focused on this agenda. A broadly representative group of participants reflected strong consensus in support of using GME outcomes data to develop better approaches to education and related policy. Implementation challenges include identifying meaningful metrics, minimizing administrative burden, addressing privacy concerns, and recognizing variability in institutional mission and capabilities. The authors recommend creating a national inventory of current data sources and initiating a pilot program to collect and share common metrics, while advancing a national effort via a “neutral” convener, such as the NASEM. The authors assert that measuring and reporting GME outcomes is a professional responsibility that must now be tackled.
Tract-Specific Volume Loss on 3T MRI in Patients With Cervical Spondylotic Myelopathy
Authors: Hopkins Benjamin S. , Weber Kenneth A. , Cloney Michael Brendan , Paliwal Monica , Parrish Todd B. , Smith Zachary A.
Published: April 2018

Study Design.

Case-control.

Objective.

The aim of this study was to understand the role of high-resolution magnetic resonance (MR) in identifying regional cord volume loss in cervical spondylotic myelopathy (CSM).

Summary of Background Data.

Preliminary studies suggest that compression of the ventral region of the cord may contribute disproportionately to CSM symptomology; however, tract-specific data are lacking in the CSM population. The current study is the first to use 3T MR imaging (MRI) images of CSM patients to determine specific volume loss at the level of detail of individual descending white matter tracts.

Methods.

Twelve patients with CSM and 14 age-matched were enrolled prospectively and underwent 3-Tesla MRI of the cervical spine. Using the high-resolution images of the spinal cord, straightening and alignment with a template was performed and specific spinal cord tract volumes were measured using Spinal Cord Tool-box version 3.0.7. Modified Japanese orthopedic association (mJOA) and Nurick disability scores were collected in a prospective manner and were analyzed in relation to descending spinal tract volumes.

Results.

Having CSM was predicted by anterior/posterior diameter, eccentricity of the cord [odds ratio (OR) 0.000000621, P = 0.004], ventral reticulospinal tract volume (OR 1.167, P = 0.063), lateral corticospinal tract volume (OR 1.034, P = 0.046), rubrospinal tract volume (OR 1.072, P = 0.011), and ventrolateral reticulospinal tract volume (OR 1.474, P = 0.005) on single variable logistic regression. Single variable linear regression showed decreases in anterior/posterior spinal cord diameter (P = 0.022), ventral reticulospinal tract volumes (P = 0.007), and ventrolateral reticulospinal tract volumes (P = 0.017) to significantly predict worsening mJOA scores. Similarly, decreases in ventral reticulospinal tract volumes significantly predicted increasing Nurick scores (P = 0.039).

Conclusion.

High-resolution 3T MRI can detect tract-specific volume loss in descending spinal cord tracts in CSM patients. Anterior/posterior spinal cord diameter, ventral reticulospinal tract, ventrolateral reticulospinal tract, lateral corticospinal tract, and rubrospinal tract volume loss are associated with CSM symptoms.

Level of Evidence: 2
Prognostic Factors of Patients With Malignant Epithelioid Vascular Tumors in the Spine
Authors: Xu Kehan , Liu Yujie , Li Bo , Li Jialin , Zhang Hao , Zhao Yuechao , Huang Quan , Wei Haifeng , Xiao Jianru
Published: April 2018

Study Design.

A retrospective study of 46 patients with malignant epithelioid vascular tumors (MEVT) in the spine was performed.

Objective.

The purpose of this study was to illustrate the clinic characteristics of MEVT in the spine and to discuss prognostic factors by survival analysis.

Summary of Background Data.

MEVT in the spine is relatively uncommon, and there is little published information regarding this subject. Therefore, prognostic factors of this disease are still controversial.

Method.

The univariate and multivariate analysis of various clinic characteristics were performed to identify the independent factor that affects prognosis for patients with MEVT in the spine who underwent surgical treatment in Changzheng Hospital Orthopedics Oncological Center (CHOOC) between 2005 and 2015. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan–Meier method to identify potential prognostic factors. Factors with P values of 0.1 or less were subjected to multivariate analysis by Cox regression analysis. P values of 0.05 or less was considered statistically significant.

Result.

A total of 46 patients with MEVT in the spine were included in the study. The mean follow-up period was 42.6 months (range, 5–143 mo). Recurrence was detected in 22 patients after initial surgery in our center, whereas death in 18 patients. The univariate analysis suggested that age (<30 yr/≥30 yr), metastasis, preoperative Frankel score, postoperative Frankel score, malignant grade and resection mode were potential prognostic factors for DFS and OS. However, as they were submitted to multivariate analyses, only malignant grade and resection mode were independent prognostic factors.

Conclusion.

Total en bloc spondylectomy can significantly improve DFS for MEVT in the spine and low-grade malignancy was favorable factor for DFS. Total spondylectomy and low-grade malignancy considerably improve OS for patients with MEVT in the spine.

Level of Evidence: 4
The Morphology and Clinical Significance of the Extraforaminal Ligaments at the T1–T12 Levels
Authors: Zhao Qinghao , Zhang Weicong , Su Zhihai , Wang Min , Yang Lianjun , Zhong Enyi , Ding Zihai , Li Qingchu , Lu Hai
Published: April 2018

Study Design.

A dissection-based study of 10 embalmed human cadavers.

Objective.

The purpose of this study was to describe the extraforaminal ligaments in the exit regions of the T1–T12 intervertebral foramina and to discuss their possible clinical significance.

Summary of Background Data.

The ligaments at the lumbar intervertebral foramina have been well studied. However, detailed descriptions of the extraforaminal ligaments at the T1–T12 levels are lacking.

Methods.

Two hundred forty T1–T12 intervertebral foramina from 10 embalmed cadavers were studied. The presence of the ligament was noted. The quantity, morphology, distributions, proximal attachments, distal attachments, and spatial orientations of the extraforaminal ligaments in the exit regions of the T1–T12 intervertebral foramina were examined. The length, width, diameter, and thickness of the ligaments were measured with digital calipers by three independent investigators.

Results.

A total of 564 extraforaminal ligaments were identified in the 229 intervertebral foramina; no ligaments were found in the other 11 intervertebral foramina, resulting in an occurrence rate of extraforaminal ligaments of 95.42%. One hundred thirty-six (24.11%) of the extraforaminal ligaments were radiating ligaments, and 428 (75.89%) were transforaminal ligaments. Radiating ligaments had a tendency to be abundant at T1 and T9–T12 and sparse at T2–T8. There were 245 (43.44%) ligaments at the anterior aspect of the exit regions of the intervertebral foramina, 225 (39.89%) ligaments at the posterior aspect, 64 (11.35%) ligaments at the inferior aspect, and 30 (5.32%) ligaments at the superior aspect.

Conclusion.

In the exit region of thoracic intervertebral foramina, there are two types of extraforaminal ligaments. They may serve as a protective mechanism against traction and play a role in the positioning of the nerves in the intervertebral foramen. Transforaminal ligaments may be an underlying cause of rib or chest pain after thoracic fracture and may be of clinical importance to surgeons.

Level of Evidence: N/A
Market and organizational factors associated with hospital vertical integration into sub-acute care
Authors: Hogan Tory H. , Lemak Christy Harris , Hearld Larry R. , Sen Bisakha P. , Wheeler Jack R.C. , Menachemi Nir
Published: April 2018

Background:

Changes in payment models incentivize hospitals to vertically integrate into sub-acute care (SAC) services. Through vertical integration into SAC, hospitals have the potential to reduce the transaction costs associated with moving patients throughout the care continuum and reduce the likelihood that patients will be readmitted.

Purpose:

The purpose of this study is to examine the correlates of hospital vertical integration into SAC.

Methodology/Approach:

Using panel data of U.S. acute care hospitals (2008–2012), we conducted logit regression models to examine environmental and organizational factors associated with hospital vertical integration. Results are reported as average marginal effects.

Findings:

Among 3,775 unique hospitals (16,269 hospital-year observations), 25.7% vertically integrated into skilled nursing facilities during at least 1 year of the study period. One measure of complexity, the availability of skilled nursing facilities in a county (ME = −1.780, p < .001), was negatively associated with hospital vertical integration into SAC. Measures of munificence, percentage of the county population eligible for Medicare (ME = 0.018, p < .001) and rural geographic location (ME = 0.069, p < .001), were positively associated with hospital vertical integration into SAC. Dynamism, when measured as the change county population between 2008 and 2011 (ME = 1.19e−06, p < .001), was positively associated with hospital vertical integration into SAC. Organizational resources, when measured as swing beds (ME = 0.069, p < .001), were positively associated with hospital vertical integration into SAC. Organizational resources, when measured as investor owned (ME = −0.052, p < .1) and system affiliation (ME = −0.041, p < .1), were negatively associated with hospital vertical integration into SAC.

Practice Implications:

Hospital adaption to the changing health care landscape through vertical integration varies across market and organizational conditions. Current Centers for Medicare and Medicaid reimbursement programs do not take these factors into consideration. Vertical integration strategy into SAC may be more appropriate under certain market conditions. Hospital leaders may consider how to best align their organization’s SAC strategy with their operating environment.
Rest Among African American Women
Authors: Herbert Harris Eboni T. , Hillfinger Messias DeAnne K. , Timmons Shirley M. , Felder Tisha M. , Estrada Robin Dawson
Published: April 2018

Effective health promotion among African American women requires knowledge and understanding of cultural influences and practices. This scoping review focused on rest, related concepts, and cultural perspectives and practices. We found a lack of conceptual distinction between fatigue and sleep and limited research on cultural meanings and practices of rest.
Use of the Modified Shuttle Walk Test During Inpatient Pediatric Cystic Fibrosis Pulmonary Exacerbation Treatment
Authors: Paranjape Shruti M. , Carson Kathryn A. , Demissie Seifu M. , Loosen Holly , Vela Kerry , Mogayzel Peter J.
Published: April 2018

Purpose:

Exercise improves pulmonary function and physical conditioning in cystic fibrosis. Exercise capacity was assessed in the inpatient setting to determine whether pulmonary exacerbation treatment with intravenous antibiotics, airway clearance, and exercise would improve exercise capacity independently of lung function.

Methods:

Exercise capacity was measured at hospital admission and hospital discharge by numbers of completed shuttles using the Modified Shuttle Walk Test (MSWT). Resting heart rate, oxyhemoglobin saturation, and assessments of breathlessness and perceived exertion were measured before and after exercise. Pulmonary function tests were obtained on the day of hospital admission and within 2 weeks of hospital discharge.

Results:

Fifty-four children performed the MSWT at hospital admission and hospital discharge. Exercise capacity increased by 15.9% during hospitalization, and lung function, measured as a percentage of the predicted forced expiratory volume in 1 second, by 15.7% during intravenous antibiotic treatment. Children with higher exercise capacity showed greater lung function (r = 0.42, P < .001) and lower preexercise resting heart rate at both hospital admission (r = −0.25, P = .03) and hospital discharge (r = −0.30, P = .007). No differences in breathlessness or perceived exertion were observed.

Conclusions:

Exercise capacity and physical conditioning improved during early pulmonary exacerbation treatment. The MSWT can be used safely to assess changes in exercise capacity during hospitalization.
Reliability, Internal Consistency, and Minimal Detectable Change of the American Physical Therapy Association Professionalism in Physical Therapy: Core Values Self-Assessment
Authors: Anderson Deborah K. , Hall Kathy D.
Published: April 2018

Introduction.

The American Physical Therapy Association identified professionalism as a key component of the professions' growth and advancement in the 21st Century. Physical therapist education programs are using the professionalism in Physical Therapy: Core Values Self-Assessment (PCVSA) for the evaluation of their students and for research. The objective of this study was to determine the extent to which the PCVSA provides a reliable measurement of professionalism in physical therapist students.

Methods.

The study sample consisted of 267 previously completed PCVSAs from physical therapist (PT) students and 29 paired PCVSAs from a current cohort of PT students. This quantitative, descriptive study examined the reliability, internal consistency, and minimal detectible change of scores from the PCVSA. Scores from previously completed PCVSAs were used to investigate internal consistency reliability using Cronbach's alpha. Scores of PCVSA from current students were used to examine test–retest reliability using the intraclass correlation coefficient (ICC) and standard error of measurement. Minimal detectable change scores were also calculated.

Results.

The total PCVSA score had excellent score consistency (α = 0.97) and stability (ICC = 0.90; 95% confidence interval [CI] = 0.78–0.95). Standard error of measurement on the total score was 5.4 points. Minimal detectable change score at the 90% CI was 13 points (95% CI was 15 points).

Discussion and Conclusion.

Utility of the total PCVSA score for formative assessment of professionalism of PT students is supported. Minimal detectable change scores can be used to track professionalism change over time. The PCVSA should not be used for high stakes decisions regarding student progression due to items that may not be appropriate for students.
Improvement in Patient-reported Hearing After Treatment With Bevacizumab in People With Neurofibromatosis Type 2
Authors: Huang Victoria , Bergner Amanda L. , Halpin Chris , Merker Vanessa L. , Sheridan Monica R. , Widemann Brigitte C. , Blakeley Jaishri O. , Plotkin Scott R.
Published: April 2018

Objective:

Assess patient-reported outcomes (PRO) for hearing and tinnitus relative to clinical hearing assessment in people with neurofibromatosis 2 (NF2) associated hearing loss.

Study Design:

Prospective, open label, phase-II clinical trial with PRO administered pre-, post-, and after treatment.

Setting:

Three tertiary referral centers.

Patients:

Fourteen patients with NF2, median age of 30 years (range, 14–79 yr) and progressive hearing loss (median baseline word recognition score, 60%; range, 13–82%). Half of these patients achieved objective hearing response (word recognition score improved beyond the 95% critical difference versus baseline).

Intervention:

Bevacizumab 7.5 mg/kg was administered every 3 weeks for 48 weeks, followed by surveillance for 24 weeks off-drug.

Main Outcome Measures:

Speech, spatial, and qualities of hearing scale (SSQ) and tinnitus reaction questionnaire (TRQ) to assess hearing difficulties in life situations and tinnitus related distress.

Results:

Patient-reported speech understanding and auditory quality improved with bevacizumab treatment and were significantly correlated with word recognition scores, but not pure tone threshold average. There was no change in spatial perception after treatment. Reduction in tinnitus distress after treatment with bevacizumab did not reach statistical significance.

Conclusion:

Participants had reductions in hearing difficulty during treatment with bevacizumab, suggesting that patients subjectively experience hearing-related benefit mirroring clinical hearing assessments. We suspect the lack of significant reduction in tinnitus distress is related to small sample size and low intensity of distress in our sample. These data highlight the usefulness of PRO measures to assess benefits of treatment in the setting of NF2-associated hearing loss.
Oval Window Size and Shape: a Micro-CT Anatomical Study With Considerations for Stapes Surgery
Authors: Zdilla Matthew J. , Skrzat Janusz , Kozerska Magdalena , Leszczyński Bartosz , Tarasiuk Jacek , Wroński Sebastian
Published: April 2018

Background:

The oval window is an important structure with regard to stapes surgeries, including stapedotomy for the treatment of otosclerosis. Recent study of perioperative imaging of the oval window has revealed that oval window niche height can indicate both operative difficulty and subjective discomfort during otosclerosis surgery. With regard to shape, structures incorporated into the oval window niche, such as cartilage grafts, must be compatible with the shape of the oval window. Despite the clinical importance of the oval window, there is little information regarding its size and shape.

Methods:

This study assessed oval window size and shape via micro-computed tomography paired with modern morphometric methodology in the fetal, infant, child, and adult populations. Additionally, the study compared oval window size and shape between sexes and between left- and right-sided ears.

Results:

No significant differences were found among traditional morphometric parameters among age groups, sides, or sexes. However, geometric morphometric methods revealed shape differences between age groups. Further, geometric morphometric methods provided the average oval window shape and most-likely shape variance.

Conclusion:

Beyond demonstrating oval window size and shape variation, the results of this report will aid in identifying patients among whom anatomical variation may contribute to surgical difficulty and surgeon discomfort, or otherwise warrant preoperative adaptations for the incorporation of materials into and around the oval window.