bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-Time Immune Monitoring to Guide Plasmid DNA Vaccination Schedule Targeting Prostatic Acid Phosphatase in Patients with Castration-Resistant Prostate Cancer
Authors: McNeel Douglas G. , Becker Jordan T. , Eickhoff Jens C. , Johnson Laura E. , Bradley Eric , Pohlkamp Isabel , Staab Mary Jane , Liu Glenn , Wilding George , Olson Brian M. 
Published: May 2014

Abstract
Purpose: We have previously reported that a DNA vaccine encoding prostatic acid phosphatase (PAP) could elicit PAP-specific T cells in patients with early recurrent prostate cancer. In the current pilot trial, we sought to evaluate whether prolonged immunization with regular booster immunizations, or “personalized” schedules of immunization determined using real-time immune monitoring, could elicit persistent, antigen-specific T cells, and whether treatment was associated with changes in PSA doubling time (PSA DT).
Experimental Design: Sixteen patients with castration-resistant, nonmetastatic prostate cancer received six immunizations at 2-week intervals and then either quarterly (arm 1) or as determined by multiparameter immune monitoring (arm 2).
Results: Patients were on study a median of 16 months; four received 24 vaccinations. Only one event associated with treatment &gt;grade 2 was observed. Six of 16 (38%) remained metastasis-free at 2 years. PAP-specific T cells were elicited in 12 of 16 (75%), predominantly of a Th1 phenotype, which persisted in frequency and phenotype for at least 1 year. IFNγ-secreting T-cell responses measured by ELISPOT were detectable in 5 of 13 individuals at 1 year, and this was not statistically different between study arms. The overall median fold change in PSA DT from pretreatment to posttreatment was 1.6 (range, 0.6–7.0; P = 0.036).
Conclusions: Repetitive immunization with a plasmid DNA vaccine was safe and elicited Th1-biased antigen-specific T cells that persisted over time. Modifications in the immunization schedule based on real-time immune monitoring did not increase the frequency of patients developing effector and memory T-cell responses with this DNA vaccine. Clin Cancer Res; 20(14); 3692–704. ©2014 AACR.
Ectopic Expression of Cancer–Testis Antigens in Cutaneous T-cell Lymphoma Patients
Authors: Litvinov Ivan V. , Cordeiro Brendan , Huang Yuanshen , Zargham Hanieh , Pehr Kevin , Doré Marc-André , Gilbert Martin , Zhou Youwen , Kupper Thomas S. , Sasseville Denis 
Published: May 2014

Abstract
Purpose: The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains only partially understood. A number of recent studies attempted to identify novel diagnostic markers and future therapeutic targets. One group of antigens, cancer–testis (CT) antigens, normally present solely in testicular germ cells, can be ectopically expressed in a variety of cancers. Currently, only a few studies attempted to investigate the expression of CT antigens in CTCL.
Experimental Design: In the present work, we test the expression of CT genes in a cohort of patients with CTCL, normal skin samples, skin from benign inflammatory dermatoses, and in patient-derived CTCL cells. We correlate such expression with the p53 status and explore molecular mechanisms behind their ectopic expression in these cells.
Results: Our findings demonstrate that SYCP1, SYCP3, REC8, SPO11, and GTSF1 genes are heterogeneously expressed in patients with CTCL and patient-derived cell lines, whereas cTAGE1 (cutaneous T-cell lymphoma-associated antigen 1) was found to be robustly expressed in both. Mutated p53 status did not appear to be a requirement for the ectopic expression of CT antigens. While T-cell stimulation resulted in a significant upregulation of STAT3 and JUNB expression, it did not significantly alter the expression of CT antigens. Treatment of CTCL cells in vitro with vorinostat or romidepsin histone deacetylase inhibitors resulted in a significant dose-dependent upregulation of mRNA but not protein. Further expression analysis demonstrated that SYCP1, cTAGE1, and GTSF1 were expressed in CTCL, but not in normal skin or benign inflammatory dermatoses.
Conclusions: A number of CT genes are ectopically expressed in patients with CTCL and can be used as biomarkers or novel targets for immunotherapy. Clin Cancer Res; 20(14); 3799–808. ©2014 AACR.
Hypoxia Regulates Alternative Splicing of HIF and non-HIF Target Genes
Authors: Sena Johnny A. , Wang Liyi , Heasley Lynn E. , Hu Cheng-Jun 
Published: May 2014

Abstract
Hypoxia is a common characteristic of many solid tumors. The hypoxic microenvironment stabilizes hypoxia-inducible transcription factor 1α (HIF1α) and 2α (HIF2α/EPAS1) to activate gene transcription, which promotes tumor cell survival. The majority of human genes are alternatively spliced, producing RNA isoforms that code for functionally distinct proteins. Thus, an effective hypoxia response requires increased HIF target gene expression as well as proper RNA splicing of these HIF-dependent transcripts. However, it is unclear if and how hypoxia regulates RNA splicing of HIF targets. This study determined the effects of hypoxia on alternative splicing (AS) of HIF and non-HIF target genes in hepatocellular carcinoma cells and characterized the role of HIF in regulating AS of HIF-induced genes. The results indicate that hypoxia generally promotes exon inclusion for hypoxia-induced, but reduces exon inclusion for hypoxia-reduced genes. Mechanistically, HIF activity, but not hypoxia per se is found to be necessary and sufficient to increase exon inclusion of several HIF targets, including pyruvate dehydrogenase kinase 1 (PDK1). PDK1 splicing reporters confirm that transcriptional activation by HIF is sufficient to increase exon inclusion of PDK1 splicing reporter. In contrast, transcriptional activation of a PDK1 minigene by other transcription factors in the absence of endogenous HIF target gene activation fails to alter PDK1 RNA splicing.
Implications: This study demonstrates a novel function of HIF in regulating RNA splicing of HIF target genes. Mol Cancer Res; 12(9); 1233–43. ©2014 AACR.
MIF Antagonist (CPSI-1306) Protects against UVB-Induced Squamous Cell Carcinoma
Authors: Nagarajan Priyadharsini , Tober Kathleen L. , Riggenbach Judith A. , Kusewitt Donna F. , Lehman Amy M. , Sielecki Thais , Pruitt James , Satoskar Abhay R. , Oberyszyn Tatiana M. 
Published: May 2014

Abstract
Macrophage migration inhibitory factor (MIF) is a homotrimeric proinflammatory cytokine implicated in chronic inflammatory diseases and malignancies, including cutaneous squamous cell carcinomas (SCC). To determine whether MIF inhibition could reduce UVB light–induced inflammation and squamous carcinogenesis, a small-molecule MIF inhibitor (CPSI-1306) was utilized that disrupts homotrimerization. To examine the effect of CPSI-1306 on acute UVB-induced skin changes, Skh-1 hairless mice were systemically treated with CPSI-1306 for 5 days before UVB exposure. In addition to decreasing skin thickness and myeloperoxidase (MPO) activity, CPSI-1306 pretreatment increased keratinocyte apoptosis and p53 expression, decreased proliferation and phosphohistone variant H2AX (γ-H2AX), and enhanced repair of cyclobutane pyrimidine dimers. To examine the effect of CPSI-1306 on squamous carcinogenesis, mice were exposed to UVB for 10 weeks, followed by CPSI-1306 treatment for 8 weeks. CPSI-1306 dramatically decreased the density of UVB-associated p53 foci in non–tumor-bearing skin while simultaneously decreasing the epidermal Ki67 proliferation index. In addition to slowing the rate of tumor development, CPSI-1306 decreased the average tumor burden per mouse. Although CPSI-1306–treated mice developed only papillomas, nearly a third of papillomas in vehicle-treated mice progressed to microinvasive SCC. Thus, MIF inhibition is a promising strategy for prevention of the deleterious cutaneous effects of acute and chronic UVB exposure.
Implications: Macrophage migration inhibitory factor is a viable target for the prevention of UVB-induced cutaneous SSCs. Mol Cancer Res; 12(9); 1292–302. ©2014 AACR.
Home‐Based Walking Exercise in Peripheral Artery Disease: 12‐Month Follow‐up of the Goals Randomized Trial
Authors: McDermott Mary M. , Guralnik Jack M. , Criqui Michael H. , Ferrucci Luigi , Zhao Lihui , Liu Kiang , Domanchuk Kathryn , Spring Bonnie , Tian Lu , Kibbe Melina , Liao Yihua , Lloyd Jones Donald , Rejeski W. Jack 
Published: May 2014

Background

We studied whether a 6‐month group‐mediated cognitive behavioral (
GMCB
) intervention for peripheral artery disease (
PAD
) participants, which promoted home‐based walking exercise, improved 6‐minute walk and other outcomes at 12‐month follow‐up, 6 months after completing the intervention, compared to a control group.

Methods and Results

We randomized
PAD
participants to a
GMCB
intervention or a control group. During phase I (months 1 to 6), the intervention used group support and self‐regulatory skills during weekly on‐site meetings to help participants adhere to home‐based exercise. The control group received weekly on‐site lectures on topics unrelated to exercise. Primary outcomes were measured at the end of phase I. During phase II (months 7 to 12), each group received telephone contact. Compared to controls, participants randomized to the intervention increased their 6‐minute walk distance from baseline to 12‐month follow‐up, (from 355.4 to 381.9 m in the intervention versus 353.1 to 345.6 m in the control group; mean difference=+34.1 m; 95% confidence interval [
CI]
=+14.6, +53.5;
P
<0.001) and their Walking Impairment Questionnaire (
WIQ
) speed score (from 36.1 to 46.5 in the intervention group versus 34.9 to 36.5 in the control group; mean difference =+8.8; 95%
CI
=+1.6, +16.1;
P
=0.018). Change in the
WIQ
distance score was not different between the 2 groups at 12‐month follow‐up (
P
=0.139).

Conclusions

A weekly on‐site
GMCB
intervention that promoted home‐based walking exercise intervention for people with
PAD
demonstrated continued benefit at 12‐month follow‐up, 6 months after the
GMCB
intervention was completed.

Clinical Trial Registration

URL:
ClinicalTrials.gov
. Unique identifier: NCT00693940.
Impaired Numerical Ability Affects Supra-Second Time Estimation
Authors: Gilaie-Dotan Sharon , Rees Geraint , Butterworth Brian , Cappelletti Marinella 
Published: May 2014

It has been suggested that the human ability to process number and time both rely on common magnitude mechanisms, yet for time this commonality has mainly been investigated in the sub-second rather than longer time ranges. Here we examined whether number processing is associated with timing in time ranges greater than a second. Specifically, we tested long duration estimation abilities in adults with a developmental impairment in numerical processing (dyscalculia), reasoning that any such timing impairment co-occurring with dyscalculia may be consistent with joint mechanisms for time estimation and number processing. Dyscalculics and age-matched controls were tested on supra-second temporal estimation (12 s), a difficulty-matched non-temporal control task, as well as mathematical abilities. Consistent with our hypothesis, dyscalculics were significantly impaired in supra-second duration estimation but not in the control task. Furthermore, supra-second timing ability positively correlated with mathematical proficiency. All participants reported that they used counting to estimate time, although no specific instructions were given with respect to counting. These results suggest that numerical processing and supra-second temporal estimation share common mechanisms. However, since this conclusion is also based on subjective observations, further work needs to be done to determine whether mathematical impairment co-occurs with supra-second time estimation impairment when counting is not involved in and is objectively controlled for during supra-second timing. We hypothesize that counting, that does not develop normally in dyscalculics, might underlie and adversely affect dyscalculics’ supra-second time estimation performance, rather than an impairment of a magnitude mechanism or the internal clock pacemaker.
A world revision of the bee fly tribe Usiini (Diptera, Bombyliidae) Part 2: Usia sensu stricto
Authors: GIBBS DAVID 
Published: May 2014

This is the second part of a world revision of the genera Usia Latreille and Parageron Paramonov, of the tribe Usiini Becker, and covers the pale-haired species, the Usia sensu stricto group. Usia sensu stricto as defined here contains 24 species of which 16 species fall into two monophyletic groups, the U. lata group with 10 species and the U. florea group with six species. Eight species cannot be placed in either of these two groups, four of them form two pairs of sibling species while the remaining four species have no clear affinities. Of the 25 formerly available names that belong in Usia sensu stricto, U. putilla Becker stat. rev., previously synonymised under U. angustifrons, is reinstated as a full species. U. sicula Egger syn. nov., is synonymised under U. manca Loew, U. anus Becker syn. nov., is synonymised under U. vestita Macquart and U. claripennis Macquart syn. nov., is synonymised under U. atrata (Fabricius). Usia vicina Macquart, formerly placed as a synonym of U. atrata, is shown to be a junior synonym of U. aenea Rossi. Five new species are described, U. anatoliensis sp. nov., U. annetteae sp. nov., U. greatheadi sp. nov., U. maghrebensis sp. nov. and U. cornigera sp. nov. Both the male and female genitalia are illustrated in detail for 21 species, female only in the cases of U. calva Loew and U. notata Loew and male only for U. incognita Paramonov.
South Asian Summer Monsoon and the Eastern Mediterranean Climate: The Monsoon–Desert Mechanism in CMIP5 Simulations
Authors: Cherchi Annalisa , Annamalai H. , Masina Simona , Navarra Antonio 
Published: May 2014

AbstractDry summers over the eastern Mediterranean are characterized by strong descent anchored by long Rossby waves, which are forced by diabatic heating associated with summer monsoon rainfall over South Asia. The large-scale teleconnection between rising and subsiding air masses is referred to as the “monsoon–desert mechanism.” This study evaluates the ability of the phase 5 of the Coupled Model Intercomparison Project (CMIP5) models in representing the physical processes involved in this mechanism.An evaluation of statistics between summer climatologies of monsoon diabatic heating and that of vertical velocity over the eastern Mediterranean suggests a linear relationship. Despite large spatial diversity in monsoon heating, descent over the Mediterranean is coherently located and realistic in intensity. To measure the sensitivity of descent to the diversity in the horizontal and vertical distribution of monsoon heating, a series of linear atmosphere model experiments are performed. It is shown that column-integrated heating over both the Bay of Bengal and the Arabian Sea provides the largest descent with a more realistic spatial pattern. In the vertical, CMIP5 models underestimate the diabatic heating at upper levels, while they overestimate it at lower levels, resulting in a weaker forced response and weaker associated descent over the Mediterranean. A moist static energy budget analysis applied to CMIP5 suggests that most models capture the dominant role of horizontal temperature advection and radiative fluxes in balancing descent over the Mediterranean. Based on the objective analysis herein, a subset of models is identified that captures the teleconnection for reasons consistent with observations. The recognized processes vary at interannual time scales as well, with imprints of severe weak/strong monsoons noticeable over the Mediterranean.
Endoscopic Gastrocnemius Recession for the Treatment of Isolated Gastrocnemius Contracture
Authors: Phisitkul Phinit , Rungprai Chamnanni , Femino John E. , Arunakul Marut , Amendola Annunziato 
Published: May 2014

Background: Endoscopic gastrocnemius recession has been proposed as a minimally invasive technique for the treatment of isolated gastrocnemius contracture. We report on the safety and efficacy of endoscopic gastrocnemius recession, as an isolated procedure or combined with other concomitant procedures in terms of improvement in ankle dorsiflexion, functional outcome, and postoperative morbidities. Methods: The data were prospectively collected in this case series. Endoscopic gastrocnemius recession was performed by a single surgeon in 320 consecutive patients (344 feet) who were diagnosed with isolated gastrocnemius contracture and failed nonoperative treatments between March 2009 and December 2012. There were 180 women and 140 men with mean age, 47.1 ± 15.7 years. The minimum follow-up was 1 year (mean, 18 months; range, 12 to 53 months). Pre- and postoperative ankle dorsiflexion, pain (Visual Analog Scale [VAS]), SF-36, and Foot Function Index (FFI) were obtained and compared using paired sample t test and Wilcoxon signed-rank test. Results: The mean ankle dorsiflexion significantly improved from −0.8 ± 5.4 degrees preoperatively to 11.0 ± 6.6 degrees at average of 13 months postoperatively (n = 294) ( P < .001). Complete preoperative and 1-year postoperative pain (VAS) (n = 274) and functional outcome scores (n = 185) were collected when possible. The mean pain (VAS) decreased from 7/10 to 3/10 postoperatively (all P < .01). The mean SF-36 including physical component summary score (PCS) and mental component summary score (MCS) increased from 34 and 44 to 45 and 51, respectively (P < .01 for both PCS and MCS). The mean FFI improved from 63 to 42 for pain, 63 to 43 for disability, 68 to 44 for activity limitation, and 61 to 41 for total score postoperatively (all P < .01). Postoperative morbidity included weakness of ankle plantarflexion (N = 11/320; 3.1% respectively) and sural nerve dysesthesia (N = 10/320; 3.4%). Wound complications or Achilles tendon rupture did not occur. There was no difference in the average improvement in ankle dorsiflexion, outcome scores, and rate of complications between the isolated and combined procedures. Conclusion: Endoscopic gastrocnemius recession demonstrated promising results in the treatment of isolated gastrocnemius contracture. Ankle dorsiflexion was significantly improved with minimal morbidity. The procedure was found effective in improving functional outcomes and relieving pain as a sole operative treatment and as a part of combined procedures in our patients. Level of Evidence: Level IV, case series.
Quantification of Shear Stresses Within a Transtibial Prosthetic Socket
Authors: Schiff Adam , Havey Robery , Carandang Gerard , Wickman Amy , Angelico John , Patwardhan Avinash , Pinzur Michael 
Published: May 2014

Background: There is a paucity of objectively recorded data delineating the pattern of weightbearing distribution within the prosthetic socket of patients with transtibial amputation. Our current knowledge is based primarily on information obtained from finite element analysis computer models. Methods: Four high-functioning transtibial amputees were fit with similar custom prosthetic sockets. Three load cells were incorporated into each socket at high stress contact areas predicted by computer modeling. Dynamic recording of prosthetic socket loading was accomplished during rising from a sitting position, stepping from a 2-leg stance to a 1-leg stance, and during the initiation of walking. By comparing the loads measured at each of the 3 critical locations, anterior/posterior shear, superior/inferior shear, and end weightbearing were recorded. Results: The same load pattern in all 4 subjects was found during each of the 3 functional activities. The load transmission at the distal end of the amputation residual limbs was negligible. Consistent forces were observed in both the anterior/posterior and superior/inferior planes. Correlation coefficients were used to compare the loads measured in each of the 4 subjects, which ranged from a low of .82 to a high of .98, where a value approaching 1.0 implies a linear relationship amongst subjects. Conclusion: This experimental model appears to have accurately recorded loading within a transtibial prosthetic socket consistent with previously reported finite element analysis computer models. Clinical Relevance: This clinical model will allow objective measurement of weightbearing within the prosthetic socket of transtibial amputees and allow objective comparison of weightbearing distribution within the prosthetic sockets of patients who have undergone creation of different versions of a transtibial amputation residual limb and prosthetic socket designs.
Functional Treatment or Cast Immobilization After Minimally Invasive Repair of an Acute Achilles Tendon Rupture
Authors: Groetelaers René P. T. G. C. , Janssen Loes , van der Velden Jolanda , Wieland Arvid W. J. , Amendt Angelique G. F. M. , Geelen Peter H. J. , Janzing Heinrich M. J. 
Published: May 2014

Background: Operative repair of an acute Achilles tendon rupture (ATR) reduces the risk of re-rupture and has therefore gained popularity as a standard treatment for ATR, especially in the young and physically active patient. There is ongoing controversy over the best surgical technique and postoperative treatment. In this prospective, randomized trial, we compared cast immobilization and functional treatment with early mobilization and weightbearing after using a minimally invasive surgical technique in patients with ATR. Methods: All patients with ATR were included. Exclusion criteria were systemic immunosuppressive therapy, re-ruptures, and severe comorbidity. All included patients underwent minimally invasive surgery, after which a below-knee splint with the foot in 10 degrees of plantar flexion was applied for the first week. Patients were then randomized to the cast immobilization group (IG) for 6 weeks or to the functional group (FG) for 6 weeks. Sixty patients were included. Median age was 43 years (range, 19-65), and 78% were male. Most ATRs were sports related. Data were collected preoperatively and during the outpatient checks at 1, 3, and 6 weeks; 3 and 6 months; and 1 year. Outcome parameters were return to work or sport, complications including re-rupture, Achilles rupture performance score (ARPS), loss of strength, range of motion, subjective result, and quality-of-life (QoL) scores. Results: In our follow-up period, we did not see differences in strength, QoL scores, return to work or sports, or ARPS between the 2 treatment groups. The patients in the FG reported more complaints, mostly pain, in the first weeks after surgery, probably because of the exercise program starting 1 week postsurgery. The overall complication rate was low. In each group, we had 1 re-rupture; in the IG, however, 2 patients had a deep venous thrombosis, despite low-molecular-weight heparin. Conclusion: The minimally invasive repair of ATR was a safe and reliable technique with good results. Early mobilization seemed to be as safe as more traditional postoperative immobilization with equal patient satisfaction. Although not significantly different, we saw more major complications in the IG. Level of Evidence: Level I, prospective randomized trial.
Dorsal Approach for Plantar Plate Repair With Weil Osteotomy
Authors: Watson Troy S. , Reid Dorian Y. , Frerichs Timothy L. 
Published: May 2014

In recent years, the role of the plantar plate in lesser metatarsophalangeal joint stability has increasingly been recognized. Tearing or attenuation of the plantar plate often will result in crossover or hammertoe deformity with hyperextension of the MTP joint. Some patients are able to have resolution of painful symptoms with conservative treatment but for those that fail these measures, surgical fixation of the plantar plate is indicated. While, there have been some described techniques for direct repair of the plantar plate, we present a surgical technique through a dorsal approach with a Weil osteotomy which accomplishes great clinical correction of the plantar plate tear and associated toe deformity as well as relief of patient’s pain. Additionally, we believe this technique is safe, efficient and reproducible. Level of Evidence: Level V, expert opinion.