bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting PIM Kinase with PD1 Inhibition Improves Immunotherapeutic Antitumor T-cell Response
Authors: Chatterjee Shilpak , Chakraborty Paramita , Daenthanasanmak Anusara , Iamsawat Supinya , Andrejeva Gabriela , Luevano Libia A. , Wolf Melissa , Baliga Uday , Krieg Carsten , Beeson Craig C. , Mehrotra Meenal , Hill Elizabeth G. , Rathmell Jeffery C. , Yu Xue-Zhong , Kraft Andrew S. , Mehrotra Shikhar 
Published: October 2018

Abstract

Purpose:
Adoptive T-cell therapy (ACT) of cancer, which involves the infusion of ex vivo–engineered tumor epitope reactive autologous T cells into the tumor-bearing host, is a potential treatment modality for cancer. However, the durable antitumor response following ACT is hampered either by loss of effector function or survival of the antitumor T cells. Therefore, strategies to improve the persistence and sustain the effector function of the antitumor T cells are of immense importance. Given the role of metabolism in determining the therapeutic efficacy of T cells, we hypothesize that inhibition of PIM kinases, a family of serine/threonine kinase that promote cell-cycle transition, cell growth, and regulate mTORC1 activity, can improve the potency of T cells in controlling tumor.

Experimental Design:
The role of PIM kinases in T cells was studied either by genetic ablation (PIM1−/−PIM2−/−PIM3−/−) or its pharmacologic inhibition (pan-PIM kinase inhibitor, PimKi). Murine melanoma B16 was established subcutaneously and treated by transferring tumor epitope gp100–reactive T cells along with treatment regimen that involved inhibiting PIM kinases, anti-PD1 or both.

Results:
With inhibition of PIM kinases, T cells had significant reduction in their uptake of glucose, and upregulated expression of memory-associated genes that inversely correlate with glycolysis. In addition, the expression of CD38, which negatively regulates the metabolic fitness of the T cells, was also reduced in PimKi-treated cells. Importantly, the efficacy of antitumor T-cell therapy was markedly improved by inhibiting PIM kinases in tumor-bearing mice receiving ACT, and further enhanced by adding anti-PD1 antibody to this combination.

Conclusions:
This study highlights the potential therapeutic significance of combinatorial strategies where ACT and inhibition of signaling kinase with checkpoint blockade could improve tumor control.
Association of CD4+ Radiation-Induced Lymphocyte Apoptosis with Fibrosis and Telangiectasia after Radiotherapy in 272 Breast Cancer Patients with &gt;10-Year Follow-up
Authors: Veldwijk Marlon R. , Seibold Petra , Botma Akke , Helmbold Irmgard , Sperk Elena , Giordano Frank A. , Gürth Nicole , Kirchner Anne , Behrens Sabine , Wenz Frederik , Chang-Claude Jenny , Herskind Carsten 
Published: October 2018

Abstract

Purpose:
Radiation-induced lymphocyte apoptosis (RILA) has been suggested as a predictive assay for adverse late reactions after radiotherapy. Thus, low RILA values of T-lymphocyte subpopulations have been associated with increased risk for various endpoints at 2 to 3 years of follow-up. The purpose was to test if such associations persist for specific endpoints (subcutaneous fibrosis, telangiectasia) in breast cancer patients with at least 10 years of follow-up.
Experimental Design: Two hundred and seventy-two female patients who had received breast-conserving therapy within the German ISE study were included (median follow-up: 11.6 years). Radiotherapy-induced side effects were scored according to the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic (LENT-SOMA) classification system. RILA in the CD4+, CD8+, and natural killer (NK) subpopulations from peripheral blood was analyzed by flow cytometry. Multivariate predictive modeling was performed including relevant clinical risk factors.

Results:
Low CD4+ RILA was associated with increased risk for both fibrosis (P = 0.011) and telangiectasia (P &lt; 0.001). For fibrosis, the association was stronger outside the surgical area (Fibout; P = 0.004) than within (Fibin; P = 0.17). Predictive multivariate modeling including clinical risk factors yielded OR of 3.48 (95% confidence interval, 1.84–6.58) for any fibrosis and 8.60 (2.71–27.3) for telangiectasia. Addition of CD4+ RILA to the clinical variables improved discrimination (c statistics) from 0.62 to 0.68 for any fibrosis, 0.62 to 0.66 for Fibin, 0.61 to 0.69 for Fibout, and from 0.65 to 0.76 for telangiectasia. CD8+ and NK RILA were not significantly associated with radiotherapy-related late reactions.

Conclusions:
The results provide first evidence that low CD4+ RILA is associated with increased subcutaneous fibrosis and telangiectasia even after 10 years. This supports the potential usefulness for predicting individual clinical risk.
Thyroid Nodule DNA Methylation Signatures: An Important Diagnostic Annotation
Authors: Mitmaker Elliot J. , Tabah Roger , How Jacques 
Published: October 2018

Abstract
Molecular profiling in thyroid cancer has made significant progress in part due to advances in somatic mutation profiling. Yet, differentiating benign from malignant thyroid nodules remains elusive. A unique set of DNA methylation signatures has the potential of improving thyroid cancer molecular diagnostics based on the DNA methylome.
See related article by Yim et al., p. 544
Fecundity, embryo size and embryo loss in the estuarine shrimp Salmoneus carvachoi Anker, 2007 (Crustacea: Alpheidae) from a tidal mudflat in northeastern Brazil
Authors: Oliveira Mário Vitor , Costa-Souza Ana Carla , Mariano Rodolfo , Almeida Alexandre Oliveira 
Published: October 2018

Studies on fecundity and embryo size have been frequently used to infer about the reproductive potential, embryogenesis, and the energy investment in embryo production in crustaceans. These parameters are relevant to the knowledge of life-history and diversity of reproductive strategies developed by this group. This study addressed the embryo production by the estuarine shrimp Salmoneus carvachoi Anker, 2007, a poorly known caridean shrimp. We investigated whether there was (1) a correlation between fecundity and carapace length, (2) an increase in embryo volume along the embryonic development, and (3) loss of embryos along development. In addition, we investigated whether the esternite length and height and width of the pleura of the second abdominal somite were good predictors of fecundity. A total of 53 embryo-carrying individuals were collected in December 2016 and February 2017 in a tidal mudflat from the estuary of the Paripe River, Ilha de Itamaracá, Pernambuco, Brazil. The carapace length ranged from 3.23 to 4.64 mm (3.78 ± 0.26 mm). Among those, 25 individuals had embryos in initial stage, 5 in intermediate stage and 15 in final stage. Fecundity ranged from 14 to 67 (33.65 ± 12.51 embryos) and was weakly correlated with carapace length. However, fecundity was strongly correlated with the width of the second sternite and width of the pleura of the second abdominal somite. Embryo volume increased markedly (93%) from the initial to the final stage of development. This increase might be due to water uptake to facilitate the membrane rupture at the onset of larvae hatching. There was significant loss of embryos only between the initial and intermediate stage. Future studies on the embryo production by other species of Salmoneus Holthuis, 1955 are necessary to understand and compare these aspects of reproductive biology.
Effects of cover crops on soil biota, soil fertility and weeds, and Pratylenchus suppression in experimental conditions
Authors: Morales Salmerón Laura , Martín-Lammerding Diana , Tenorio Pasamón José Luis , Sánchez-Moreno Sara 
Published: October 2018

SummaryCover crops are used in Mediterranean agrosystems to reduce soil degradation and restore soil function. We carried out an experiment to test the effects of two cover crops (Brachypodium distachyonandTrifolium subterraneum, mulched or incorporated) and two bare soil controls (fertilised and unfertilised) on soil properties, biodiversity, and soil natural suppressiveness againstPratylenchus neglectusin pot microcosms. Cover crop performance, weed infestation, litter decomposition rates, soil properties, and the response of soil biota (nematode indicators, mesofauna feeding activity, enzymatic activity, and mycorrhizal spores) were measured. A short-term suppressiveness experiment was performed to determineP. neglectuscolonisation of wheat roots after each treatment.Trifolium subterraneumincorporation significantly enhanced the fungal-mediated decomposition channel and decomposition rates, but enzymatic activities and mycorrhizal spore abundances did not respond to the experimental treatments. Cover crops were effective at controlling weeds, but did not increase soil suppressiveness againstP. neglectus. Brachypodium distachyoncover cropping increased root infection.
My favourite nematode – Phasmarhabditis hermaphrodita
Authors: Rae Robbie 
Published: October 2018

Summary
The terrestrial gastropod parasitic nematode Phasmarhabditis hermaphrodita is the only nematode that evolved to infect and kill slugs and snails. Because of this ability it has been formulated into a biological control agent for gardeners. In this Forum article, the author outlines several reasons why P. hemaphrodita is a nematode that is worth studying, including its ability to control the behaviour and kill slug hosts. The author discusses how P. hemaphrodita is being developed as a model nematode to be used to study the genetic evolution of parasitism, as well as potential research ideas for the future.
The Response of Hadley Circulation Extent to an Idealized Representation of Poleward Ocean Heat Transport in an Aquaplanet GCM
Authors: Hilgenbrink Casey C. , Hartmann Dennis L. 
Published: October 2018

AbstractDeeper theoretical understanding of Hadley circulation (HC) width and the mechanisms leading to HC expansion is gained by exploring the response of a zonally symmetric slab ocean aquaplanet general circulation model (GCM) to imposed poleward ocean heat transport (OHT). Poleward OHT causes the subtropical edge of the HC to shift poleward by up to 3° compared to its position in simulations without OHT. This HC widening is interpreted as being driven by a decrease in baroclinicity near the poleward edge of the HC and is divided into three components: a decrease in baroclinicity due to 1) a systematic poleward shift of the intertropical convergence zone (ITCZ) during the seasonal cycle that drives a decrease in the angular momentum of the HC and, consequently, a weakening of the vertical shear of the zonal wind; 2) an increase in subtropical static stability and the vertical extent of the HC, both of which result from OHT’s effect on global-mean temperature; and 3) a relaxation of the meridional sea surface temperature (SST) gradient in the outer tropics and subtropics by OHT. Although the third mechanism contributes the most to the response of HC width to OHT, the contributions from the first two mechanisms each account for up to 20%–30% of the HC response. This work highlights the role of ITCZ position in producing HC expansion and in setting the climatological width of the HC, a role which has been underappreciated. This study indicates a fundamental role for baroclinicity in limiting the poleward extent of the HC.
Deep Intraseasonal Variability in the Central Equatorial Atlantic
Authors: Tuchen Franz Philip , Brandt Peter , Claus Martin , Hummels Rebecca 
Published: October 2018

AbstractBesides the zonal flow that dominates the seasonal and long-term variability in the equatorial Atlantic, energetic intraseasonal meridional velocity fluctuations are observed in large parts of the water column. We use 15 years of partly full-depth velocity data from an equatorial mooring at 23°W to investigate intraseasonal variability and specifically the downward propagation of intraseasonal energy from the near-surface into the deep ocean. Between 20 and 50 m, intraseasonal variability at 23°W peaks at periods between 30 and 40 days. It is associated with westward-propagating tropical instability waves, which undergo an annual intensification in August. At deeper levels down to about 2000 m considerable intraseasonal energy is still observed. A frequency–vertical mode decomposition reveals that meridional velocity fluctuations are more energetic than the zonal ones for periods < 50 days. The energy peak at 30–40 days and at vertical modes 2–5 excludes equatorial Rossby waves and suggests Yanai waves to be associated with the observed intraseasonal energy. Yanai waves that are considered to be generated by tropical instability waves propagate their energy from the near-surface west of 23°W downward and eastward to eventually reach the mooring location. The distribution of intraseasonal energy at the mooring position depends largely on the dominant frequency and the time, depth, and longitude of excitation, while the dominant vertical mode of the Yanai waves plays only a minor role. Observations also show the presence of weaker intraseasonal variability at 23°W below 2000 m that cannot be associated with tropical instability waves.
An Integrated Method for Determining the Oceanic Bottom Mixed Layer Thickness Based on WOCE Potential Temperature Profiles
Authors: Huang Peng-Qi , Cen Xian-Rong , Lu Yuan-Zheng , Guo Shuang-Xi , Zhou Sheng-Qi 
Published: October 2018

AbstractIn this study we examined the applicability of the threshold, curvature, maximum angle, and relative variance methods for identifying the oceanic bottom mixed layer (BML) thickness . Using full-depth temperature profiles along 17 WOCE sections covering the Atlantic, Indian, and Pacific Oceans, we found that the BML thicknesses determined based on the threshold, curvature, and maximum angle methods had wider 95% confidence intervals and much lower quality indexes compared with those based on the visual inspection (). The relative variance method appeared to perform better than the other methods because the 95% confidence interval and (0.60) values were closer to those determined based on the visual inspection, although differences were still present. We then proposed an integrated method by optimizing the possible values obtained from the four methods. The BML thicknesses determined using the integrated method were closest to those based on the visual inspection according to the higher (0.64) and more stations (71%) with . Compared with the results in previous studies, the integrated method determined the consistent BML thicknesses in most regions (e.g., the northern Atlantic), and it also effectively identified the BML thicknesses in some regions where the BML was considered to be not readily detectable (e.g., the Madeira Abyssal Plain).
Is Semantic Vigilance Impaired by Narrative Memory Demands? Theory and Applications
Authors: Epling Samantha L. , Edgar Graham K. , Russell Paul N. , Helton William S. 
Published: October 2018

Objective: Two verbal tasks were utilized in a dual-task paradigm to explore performance theories and prior dual-tasking results. Background: Both the decline in vigilance performance over time, or vigilance decrement, and limited dual-tasking ability may be explained by limited mental resources. Resource theorists would recommend removing task demands to avoid cognitive overload, while mindlessness theorists may recommend adding engaging task demands to prevent boredom. Prior research demonstrated interference between a verbal free recall and semantic vigilance task, but exploring tasks with greater ecological validity is necessary. Method: A narrative memory task and semantic vigilance task were performed individually and simultaneously. Relative performance impairments were compared to a previous dual-task pairing. Results: The semantic vigilance task caused performance degradation to the narrative memory task and vice versa. A vigilance decrement was not observed, and the interference was to a lesser extent than when the semantic vigilance task was paired with a free recall task. Conclusion: Resource theory was supported, though passive learning effects during a semantic vigilance task with novel stimuli may prevent a vigilance decrement. The interference was less than that of a previous similar dual-task pairing, but even tasks as routine as listening to a conversation or story can impair other task performance. Application: A better understanding of resource theory and dual-task performance outcomes can help inform feasible task loads and improve efficiency and safety of operators in high-risk and other professions.
Postoperative Pain Control and Opioid Usage Patterns among Patients Undergoing Thyroidectomy and Parathyroidectomy
Authors: Tharakan Theresa , Jiang Sydney , Fastenberg Judd , Ow Thomas J. , Schiff Bradley , Smith Richard V. , Mehta Vikas 
Published: October 2018

ObjectivesTo examine opioid‐prescribing patterns after endocrine surgery. To evaluate factors associated with postoperative pain and opioid use.Study DesignCross‐sectional.SettingAcademic university health system.Subjects and MethodsThe study sample included 209 patients who underwent total thyroidectomy, hemithyroidectomy, or parathyroidectomy by 4 surgeons between August 2015 and November 2017. Eighty‐nine patients completed a phone survey about postoperative pain and opioid use. Prescription, demographic, and comorbidity data were collected retrospectively. Patient characteristics associated with opioid use, use of ≥10 opioid pills, and pain score were identified via chi‐square, t test, analysis of variance, or Pearson correlation. Identified factors were further assessed with multivariable logistic and linear regression modeling.ResultsThe median numbers of opioid pills prescribed were 20 for total thyroidectomy, 25 for hemithyroidectomy, and 20 for parathyroidectomy, and the median numbers of pills used were 1.5, 2, and 0, respectively. Of 1947 total prescribed pills, 19.7% were reported to be taken. The number of pills meeting the opioid needs of 80% of these patients was 10. In multivariable analyses, older age was associated with lower odds of opioid use (odds ratio, 0.97; 95% CI, 0.94‐0.999; P =. 04) and lower pain scores (Pearson correlation coefficient, –0.05; 95% CI, –0.10 to 0.001, P =. 04). Charlson Comorbidity Index score >5 was associated with use of ≥10 pills (odds ratio, 6.62; 95% CI, 1.60‐27.50; P =. 01).ConclusionExcess opioids are often prescribed for endocrine surgery. By using an ideal pill number and understanding predictors of postoperative pain, surgeons can more adequately treat pain and limit excess opioid prescriptions.
Utility of Intraoperative Frozen Section in Large Thyroid Nodules
Authors: Bollig Craig A. , Jorgensen Jeffrey B. , Zitsch Robert P. , Dooley Laura M. 
Published: October 2018

ObjectiveTo determine if the routine use of intraoperative frozen section (iFS) results in cost savings among patients with nodules >4 cm with nonmalignant cytology undergoing a thyroid lobectomy.Study DesignCase series with chart review; cost minimization analysis.SettingSingle academic center.Subjects and MethodsRecords were reviewed on a consecutive sample of 48 patients with thyroid nodules >4 cm and nonmalignant cytology who were undergoing thyroid lobectomy in which iFS was performed between 2010 and 2015. A decision tree model of thyroid lobectomy with iFS was created. Comparative parameters were obtained from the literature. A cost minimization analysis was performed comparing lobectomy with and without iFS and the need for completion thyroidectomy with costs estimated according to 2014 data from Medicare, the Bureau of Labor Statistics, and the Nationwide Inpatient Sample.ResultsThe overall malignancy rate was 25%, and 33% of these malignancies were identified intraoperatively. When the malignancy rates obtained from our cohort were applied, performing routine iFS was the less costly scenario, resulting in a savings of $486 per case. When the rate of malignancy identified on iFS was adjusted, obtaining iFS remained the less costly scenario as long as the rate of malignancies identified on iFS exceeded 12%. If patients with follicular lesions on cytology were excluded, 50% of malignancies were identified intraoperatively, resulting in a savings of $768 per case.ConclusionsFor patients with nodules >4 cm who are undergoing a diagnostic lobectomy, the routine use of iFS may result in decreased health care utilization. Additional cost savings could be obtained if iFS is avoided among patients with follicular lesions.
The Role of Oral Steroids in the Treatment of Phonotraumatic Vocal Fold Lesions in Women
Authors: Amin Milan R. , Achlatis Stratos , Gherson Shirley , Fang Yixin , Wang Binhuan , Born Hayley , Branski Ryan C. , Johnson Aaron M. 
Published: October 2018

Objectives(1) To determine the short‐term effectiveness of oral steroids in women with benign vocal fold lesions and (2) to determine the effectiveness of adjuvant oral steroids in women undergoing voice therapy for benign vocal fold lesions.Study DesignRandomized, double‐blind, placebo‐controlled clinical trial.SettingTertiary voice care center.Subjects and MethodsThirty‐six patients undergoing voice therapy for the treatment of phonotraumatic vocal fold lesions randomly received either a 4‐day course of oral steroids or a placebo prior to initiating voice therapy. Voice Handicap Index–10 (VHI‐10) scores, video and audioperceptual analyses, acoustic and aerodynamic analyses at baseline, and patient perception of improvement after a short course of steroids or a placebo and at the conclusion of voice therapy were collected.ResultsThirty patients completed the study, of whom 27 (only female) were analyzed. The primary outcome measure, VHI‐10, did not improve after the 4‐day course of steroids or placebo. Secondary measures similarly showed no improvement with steroids relative to placebo. Voice therapy demonstrated a positive effect on both VHI‐10 and patient‐perceived improvement of voice in all subjects.ConclusionA short course of oral steroids did not benefit women with phonotraumatic vocal fold lesions. In addition, steroids had little beneficial effect when used adjunctively with voice therapy in this patient cohort.
Spectroscopic Analysis of Human Tracheal Tissue during Decellularization
Authors: Tint Derrick , Stabler Collin T. , Hanifi Arash , Yousefi Farzad , Linkov Gary , Hy Kenneth , Soliman Ahmed M. S. , Pleshko Nancy 
Published: October 2018

ObjectiveTo use mid‐infrared (IR) spectroscopy to assess changes in the cartilaginous framework of human trachea during decellularization.Study DesignLaboratory‐based study.SettingResearch laboratory.MethodsSix cadaveric human tracheas were decellularized using a detergent enzymatic method (DEM). Tissue samples were obtained from each specimen after 0, 1, 10, and 25 DEM cycles for histologic and spectroscopic analysis. Decellularization was confirmed using hematoxylin and eosin (H&E) and 2‐(4‐amidinophenyl)‐1H‐indole‐6‐carboxamidine (DAPI) staining. Changes in cartilaginous framework were examined using Fourier transform infrared imaging spectroscopy (FT‐IRIS) and an attenuated total reflectance (ATR) probe in the mid‐IR frequencies. Results were statistically analyzed using 1‐way analysis of variance (ANOVA) and principal component analysis (PCA).ResultsSix decellularized tracheal scaffolds were successfully created using a DEM protocol. Histologic examination showed near‐complete nuclear loss following 25 DEM cycles. As observed with FT‐IRIS analysis, the collagen absorbance signal (1336 cm−1) was predominantly in the perichondria and remained stable after 25 DEM cycles (P =. 132), while the absorbance from sugar rings in proteoglycans and nucleic acids in hyaline cartilage (1080 cm−1) showed a significant decrease after 1 DEM cycle (P =. 0007). Examination of the luminal surface of the trachea with an ATR probe showed raw mid‐IR spectra consistent with cartilage. PCA showed significant separation of spectra corresponding to treatment cycle along the principal components 1 and 2.ConclusionMid‐IR spectroscopy is a viable method of monitoring changes in extracellular matrix components during the decellularization of human trachea.