Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy
Tumor-infiltrating lymphocytes (TILs) are associated with better clinical outcomes in many tumors. TILs represent a cell-mediated immune response against the carcinoma. CD8+ TILs are a crucial component of cell-mediated immunity. The significance of CD8+ TILs has not been reported respectively in organ- and non-organ-confined urothelial carcinoma (UC) of the bladder. We explored the prognostic value of CD8+ TILs in the two groups. The presence of CD8+ TILs was assessed by immunohistochemical staining of whole tissue sections from 75 organ and 51 non-organ-confined disease patients with long-term follow-up, and its correlation with clinicopathological features and overall survival (OS) was determined. The CD8+ TIL immunohistochemical staining score was 0 (<1%), 1 (≥1%), 2 (≥5%), or 3 (≥10%) based on the percentage of positively stained cells out of total cells. A patient was considered CD8 negative if the score was 0. There were no associations between CD8+ TILs and age, sex, nuclear grade, and adjuvant or neoadjuvant chemotherapy in organ- and non-organ-confined disease. The presence of CD8+ TILs was seen more frequently in pTa-1 than pT2 stage (p = 0.033) in organ-confined disease. No associations between CD8+ TILs and pT stage, pN stage were found in non-organ-confined disease. CD8+ TILs were associated with better OS (log-rank test, P = 0.036) in non-organ-confined disease, but with poorer OS (log-rank test, P = 0.040) in organ-confined disease by the Kaplan–Meier method. In multivariate analysis, CD8+ TILs were an independent favorable prognostic factor in non-organ-confined disease, but were an independent unfavorable prognostic factor in organ-confined disease. These results suggest that CD8+ TILs have clinically significant anti-tumor activity in non-organ-confined disease, but may have pro-tumor activity in organ-confined disease. Therefore, we should be cautious if CD8+ TILs are aimed to be exploited in the treatment of bladder cancer.
Zhang et al. (2017) Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy. PeerJ 5:e3921 https://doi.org/10.7717/peerj.3921
A retrospective study: does upper airway morphology differ between non-positional and positional obstructive sleep apnea?
Objective The objective of this study was to explore the differences in upper airway morphology between positional (POSA) and non-positional (NPOSA) obstructive sleep apnea. Methods This retrospective study enrolled 75 patients (45 NPOSA and 30 POSA) who underwent polysomnography (PSG) and computed tomography (CT). The differences in, and relationships of, the PSG values and CT data between POSA and NPOSA were analyzed. Results Significant (p < 0.05) differences between the two groups were found in the apnea/hypopnea index (AHI), lateral-AHI (L-AHI), soft palate length (SPL), cross-sectional palatopharyngeal area, and the coronal diameter (CD) of the palatopharyngeal area at the narrowest part of the glossopharynx, which were all higher in POSA, except for SPL, AHI, and L-AHI. L-AHI was correlated with the cross-sectional area (r = − 0.306, p = 0.008) and CD (r = − 0.398, p < 0.001) of the palatopharyngeal area, the cross-sectional area (r = − 0.241, p = 0.038) and CD (r = − 0.297, p = 0.010) of the narrowest level of the glossopharynx, the CD of the glossopharynx (r = 0.284, p = 0.013), body mass index (BMI, r = 0.273, p = 0.018), SPL (r = 0.284, p = 0.014), and vallecula-tip of tongue (r = 0.250, p = 0.030). The SPL and CD at the narrowest part of the glossopharynx were included in the simplified screening model. Conclusions In NPOSA, the CD of the upper airway was smaller, and the soft palate was longer, than in POSA. These differences may play significant roles in explaining the main differences between NPOSA and POSA.
Jiao et al. (2017) A retrospective study: does upper airway morphology differ between non-positional and positional obstructive sleep apnea?. PeerJ 5:e3918 https://doi.org/10.7717/peerj.3918
Neurodynamic mobilization and foam rolling improved delayed-onset muscle soreness in a healthy adult population: a randomized controlled clinical trial
Objectives Compare the immediate effects of a Neurodynamic Mobilization (NM) treatment or foam roller (FR) treatment after DOMS. Design Double blind randomised clinical trial. Setting The participants performed 100 drop jumps (5 sets of 20 repetitions, separated by 2 min rests) from a 0.5-m high box in a University biomechanics laboratory to induce muscle soreness. The participants were randomly assigned in a counter-balanced fashion to either a FR or NM treatment group. Participants Thirty-two healthy subjects (21 males and 11 females, mean age 22.6 ± 2.2 years) were randomly assigned into the NM group (n = 16) or the FR group (n = 16). Main Outcome Measures The numeric pain rating scale (NPRS; 0–10), isometric leg strength with dynamometry, surface electromyography at maximum voluntary isometric contraction (MVIC) and muscle peak activation (MPA) upon landing after a test jump were measured at baseline, 48 h after baseline before treatment, and immediately after treatment. Results Both groups showed significant reduction in NPRS scores after treatment (NM: 59%, p < .01; FR: 45%, p < .01), but no difference was found between them (p > .05). The percentage change improvement in the MVIC for the rectus femoris was the only significant difference between the groups (p < 0.05) at post-treatment. After treatment, only the FR group had a statistically significant improvement (p < 0.01) in strength compared to pre-treatment. Conclusion Our results illustrate that both treatments are effective in reducing pain perception after DOMS whereas only FR application showed differences for the MVIC in the rectus femoris and strength.
Romero-Moraleda et al. (2017) Neurodynamic mobilization and foam rolling improved delayed-onset muscle soreness in a healthy adult population: a randomized controlled clinical trial. PeerJ 5:e3908 https://doi.org/10.7717/peerj.3908
Multigene phylogeny of the scyphozoan jellyfish family Pelagiidae reveals that the common U.S. Atlantic sea nettle comprises two distinct species (Chrysaora quinquecirrha and C. chesapeakei)
Background Species of the scyphozoan family Pelagiidae (e.g., Pelagia noctiluca, Chrysaora quinquecirrha) are well-known for impacting fisheries, aquaculture, and tourism, especially for the painful sting they can inflict on swimmers. However, historical taxonomic uncertainty at the genus (e.g., new genus Mawia) and species levels hinders progress in studying their biology and evolutionary adaptations that make them nuisance species, as well as ability to understand and/or mitigate their ecological and economic impacts. Methods We collected nuclear (28S rDNA) and mitochondrial (cytochrome c oxidase I and 16S rDNA) sequence data from individuals of all four pelagiid genera, including 11 of 13 currently recognized species of Chrysaora. To examine species boundaries in the U.S. Atlantic sea nettle Chrysaora quinquecirrha, specimens were included from its entire range along the U.S. Atlantic and Gulf of Mexico coasts, with representatives also examined morphologically (macromorphology and cnidome). Results Phylogenetic analyses show that the genus Chrysaora is paraphyletic with respect to other pelagiid genera. In combined analyses, Mawia, sampled from the coast of Senegal, is most closely related to Sanderia malayensis, and Pelagia forms a close relationship to a clade of Pacific Chrysaora species (Chrysaora achlyos, Chrysaora colorata, Chrysaora fuscescens, and Chrysaora melanaster). Chrysaora quinquecirrha is polyphyletic, with one clade from the U.S. coastal Atlantic and another in U.S. Atlantic estuaries and Gulf of Mexico. These genetic differences are reflected in morphology, e.g., tentacle and lappet number, oral arm length, and nematocyst dimensions. Caribbean sea nettles (Jamaica and Panama) are genetically similar to the U.S. Atlantic estuaries and Gulf of Mexico clade of Chrysaora quinquecirrha. Discussion Our phylogenetic hypothesis for Pelagiidae contradicts current generic definitions, revealing major disagreements between DNA-based and morphology-based phylogenies. A paraphyletic Chrysaora raises systematic questions at the genus level for Pelagiidae; accepting the validity of the recently erected genus Mawia, as well as past genera, will require the creation of additional pelagiid genera. Historical review of the species-delineating genetic and morphological differences indicates that Chrysaora quinquecirrha Desor 1848 applies to the U.S. Coastal Atlantic Chrysaora species (U.S. Atlantic sea nettle), while the name C. chesapeakei Papenfuss 1936 applies to the U.S. Atlantic estuarine and Gulf of Mexico Chrysaora species (Atlantic bay nettle). We provide a detailed redescription, with designation of a neotype for Chrysaora chesapeakei, and clarify the description of Chrysaora quinquecirrha. Since Caribbean Chrysaora are genetically similar to Chrysaora chesapeakei, we provisionally term them Chrysaora c.f. chesapeakei. The presence of Mawia benovici off the coast of Western Africa provides a potential source region for jellyfish introduced into the Adriatic Sea in 2013.
Bayha et al. (2017) Multigene phylogeny of the scyphozoan jellyfish family Pelagiidae reveals that the common U.S. Atlantic sea nettle comprises two distinct species (Chrysaora quinquecirrha and C. chesapeakei). PeerJ 5:e3863 https://doi.org/10.7717/peerj.3863
Mysterious inhibitory cell regulator investigated and found likely to be secretogranin II related
In the context of a hunt for a postulated hormone that is tissue-mass inhibiting and reproductively associated, there is described probable relatedness to a granin protein. A 7–8 kDa polypeptide candidate (gels/MS) appeared in a bioassay-guided fractionation campaign involving sheep plasma. An N-terminal sequence of 14 amino acids was obtained for the polypeptide by Edman degradation. Bioinformatics and molecular biology failed to illuminate any ovine or non-ovine protein which might relate to this sequence. The N-terminal sequence was synthesized as the 14mer EPL001 peptide and surprisingly found to be inhibitory in an assay in vivo of compensatory renal growth in the rat and modulatory of nematode fecundity, in line with the inhibitory hormone hypothesis. Antibodies were raised to EPL001 and their deployment upheld the hypothesis that the EPL001 amino acid sequence is meaningful and relevant, notwithstanding bioinformatic obscurity. Immunohistochemistry (IHC) in sheep, rodents and humans yielded staining of seeming endocrine relevance (e.g. hypothalamus, gonads and neuroendocrine cells in diverse tissues), with apparent upregulation in certain human tumours (e.g. pheochromocytoma). Discrete IHC staining in Drosophila melanogaster embryo brain was seen in glia and in neuroendocrine cells, with staining likely in the corpus cardiacum. The search for the endogenous antigen involved immunoprecipitation (IP) followed by liquid chromatography and mass spectrometry (LC–MS). Feedstocks were PC12 conditioned medium and aqueous extract of rat hypothalamus—both of which had anti-proliferative and pro-apoptotic effects in an assay in vitro involving rat bone marrow cells, which inhibition was subject to prior immunodepletion with an anti-EPL001 antibody—together with fruit fly embryo material. It is concluded that the mammalian antigen is likely secretogranin II (SgII) related. The originally seen 7–8 kDa polypeptide is suggested to be a new proteoform of secretogranin II of ∼70 residues, SgII-70, with the anti-EPL001 antibody seeing a discontinuous epitope. The fly antigen is probably Q9W2X8 (UniProt), an uncharacterised protein newly disclosed as a granin and provisionally dubbed macrogranin I (MgI). SgII and Q9W2X8 merit further investigation in the context of tissue-mass inhibition.
Hart et al. (2017) Mysterious inhibitory cell regulator investigated and found likely to be secretogranin II related. PeerJ 5:e3833 https://doi.org/10.7717/peerj.3833
The intervals method: a new approach to analyse finite element outputs using multivariate statistics
Background In this paper, we propose a new method, named the intervals’ method, to analyse data from finite element models in a comparative multivariate framework. As a case study, several armadillo mandibles are analysed, showing that the proposed method is useful to distinguish and characterise biomechanical differences related to diet/ecomorphology. Methods The intervals’ method consists of generating a set of variables, each one defined by an interval of stress values. Each variable is expressed as a percentage of the area of the mandible occupied by those stress values. Afterwards these newly generated variables can be analysed using multivariate methods. Results Applying this novel method to the biological case study of whether armadillo mandibles differ according to dietary groups, we show that the intervals’ method is a powerful tool to characterize biomechanical performance and how this relates to different diets. This allows us to positively discriminate between specialist and generalist species. Discussion We show that the proposed approach is a useful methodology not affected by the characteristics of the finite element mesh. Additionally, the positive discriminating results obtained when analysing a difficult case study suggest that the proposed method could be a very useful tool for comparative studies in finite element analysis using multivariate statistical approaches.
Marcé-Nogué et al. (2017) The intervals method: a new approach to analyse finite element outputs using multivariate statistics. PeerJ 5:e3793 https://doi.org/10.7717/peerj.3793
Sediment microbial taxonomic and functional diversity in a natural salinity gradient challenge Remane’s “species minimum” concept
Several models have been developed for the description of diversity in estuaries and other brackish habitats, with the most recognized being Remane’s Artenminimum (“species minimum”) concept. It was developed for the Baltic Sea, one of the world’s largest semi-enclosed brackish water body with a unique permanent salinity gradient, and it argues that taxonomic diversity of macrobenthic organisms is lowest within the horohalinicum (5 to 8 psu). The aim of the present study was to investigate the relationship between salinity and sediment microbial diversity at a freshwater-marine transect in Amvrakikos Gulf (Ionian Sea, Western Greece) and assess whether species composition and community function follow a generalized concept such as Remane’s. DNA was extracted from sediment samples from six stations along the aforementioned transect and sequenced for the 16S rRNA gene using high-throughput sequencing. The metabolic functions of the OTUs were predicted and the most abundant metabolic pathways were extracted. Key abiotic variables, i.e., salinity, temperature, chlorophyll-a and oxygen concentration etc., were measured and their relation with diversity and functional patterns was explored. Microbial communities were found to differ in the three habitats examined (river, lagoon and sea) with certain taxonomic groups being more abundant in the freshwater and less in the marine environment, and vice versa. Salinity was the environmental factor with the highest correlation to the microbial community pattern, while oxygen concentration was highly correlated to the metabolic functional pattern. The total number of OTUs showed a negative relationship with increasing salinity, thus the sediment microbial OTUs in this study area do not follow Remane’s concept.
Pavloudi et al. (2017) Sediment microbial taxonomic and functional diversity in a natural salinity gradient challenge Remane’s “species minimum” concept. PeerJ 5:e3687 https://doi.org/10.7717/peerj.3687
Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα) as a potential biomarker of consumption and dual diagnosis
Background Cocaine use disorder (CUD) is a complex health condition, especially when it is accompanied by comorbid psychiatric disorders (dual diagnosis). Dual diagnosis is associated with difficulties in the stratification and treatment of patients. One of the major challenges in clinical practice of addiction psychiatry is the lack of objective biological markers that indicate the degree of consumption, severity of addiction, level of toxicity and response to treatment in patients with CUD. These potential biomarkers would be fundamental players in the diagnosis, stratification, prognosis and therapeutic orientation in addiction. Due to growing evidence of the involvement of the immune system in addiction and psychiatric disorders, we tested the hypothesis that patients with CUD in abstinence might have altered circulating levels of signaling proteins related to systemic inflammation. Methods The study was designed as a cross-sectional study of CUD treatment-seeking patients. These patients were recruited from outpatient programs in the province of Malaga (Spain). The study was performed with a total of 160 white Caucasian subjects, who were divided into the following groups: patients diagnosed with CUD in abstinence (N = 79, cocaine group) and matched control subjects (N = 81, control group). Participants were clinically evaluated with the diagnostic interview PRISM according to the DSM-IV-TR, and blood samples were collected for the determination of chemokine C-C motif ligand 11 (CCL11, eotaxin-1), interferon gamma (IFNγ), interleukin-4 (IL-4), interleukin-8 (IL-8), interleukin-17α (IL-17α), macrophage inflammatory protein 1α (MIP-1α) and transforming growth factor α (TGFα) levels in the plasma. Clinical and biochemical data were analyzed in order to find relationships between variables. Results While 57% of patients with CUD were diagnosed with dual diagnosis, approximately 73% of patients had other substance use disorders. Cocaine patients displayed greater cocaine symptom severity when they were diagnosed with psychiatric comorbidity. Regarding inflammatory factors, we observed significantly lower plasma levels of IL-17α (p < 0.001), MIP-1α (p < 0.001) and TGFα (p < 0.05) in the cocaine group compared with the levels in the control group. Finally, there was a significant primary effect of dual diagnosis on the plasma concentrations of TGFα (p < 0.05) in the cocaine group, and these levels were lower in patients with dual diagnoses Discussion IL-17α, MIP-1α and TGFα levels are different between the cocaine and control groups, and TGFα levels facilitate the identification of patients with dual diagnosis. Because TGFα reduction is associated with enhanced responses to cocaine in preclinical models, we propose TGFα as a potential biomarker of complex CUD in humans.
Maza-Quiroga et al. (2017) Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα) as a potential biomarker of consumption and dual diagnosis. PeerJ 5:e3926 https://doi.org/10.7717/peerj.3926
External validation of cut-off points for foveal thickness taking into account the intraretinal fluid using optical coherence tomography to diagnose diabetic macular oedema
Background In late 2015, cut-off points were published for foveal thickness to diagnose diabetic macular oedema taking into account the presence of intraretinal fluid using optical coherence tomography (OCT) in primary care patients (90 µm in the presence of intraretinal fluid and 310 µm otherwise). Methods This cross-sectional observational study was carried out on 134 eyes of diabetic patients treated in specialised ophthalmology services in a Spanish region in 2012–2013, to externally validate the aforementioned cut-off points. The main variable (Clinical Standard) was the diagnosis of macular oedema through indirect ophthalmoscopy and posterior segment slit-lamp biomicroscopy. As validation variables, both the foveal thickness and the presence of intraretinal fluid obtained by OCT were used. Validation was performed using bootstrapping by calculating the area under the ROC curve (AUC), sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR). Results Forty-one eyes presented diabetic macular oedema (30.6%). The bootstrapping validation parameters were: AUC, 0.88; sensitivity, 0.75; specificity, 0.95; PLR, 14.31; NLR, 0.26. These values were very similar to those of the original publication. Conclusion We have externally validated in specialised care patients the cut-off points published for the diagnosis of diabetic macular oedema. We suggest that others carry out validation studies in their communities.
Hernández-Martínez et al. (2017) External validation of cut-off points for foveal thickness taking into account the intraretinal fluid using optical coherence tomography to diagnose diabetic macular oedema. PeerJ 5:e3922 https://doi.org/10.7717/peerj.3922
The complete chloroplast genome sequence of strawberry (Fragaria × ananassa Duch.) and comparison with related species of Rosaceae
Compared with other members of the family Rosaceae, the chloroplast genomes of Fragaria species exhibit low variation, and this situation has limited phylogenetic analyses; thus, complete chloroplast genome sequencing of Fragaria species is needed. In this study, we sequenced the complete chloroplast genome of F. × ananassa ‘Benihoppe’ using the Illumina HiSeq 2500-PE150 platform and then performed a combination of de novo assembly and reference-guided mapping of contigs to generate complete chloroplast genome sequences. The chloroplast genome exhibits a typical quadripartite structure with a pair of inverted repeats (IRs, 25,936 bp) separated by large (LSC, 85,531 bp) and small (SSC, 18,146 bp) single-copy (SC) regions. The length of the F. × ananassa ‘Benihoppe’ chloroplast genome is 155,549 bp, representing the smallest Fragaria chloroplast genome observed to date. The genome encodes 112 unique genes, comprising 78 protein-coding genes, 30 tRNA genes and four rRNA genes. Comparative analysis of the overall nucleotide sequence identity among ten complete chloroplast genomes confirmed that for both coding and non-coding regions in Rosaceae, SC regions exhibit higher sequence variation than IRs. The Ka/Ks ratio of most genes was less than 1, suggesting that most genes are under purifying selection. Moreover, the mVISTA results also showed a high degree of conservation in genome structure, gene order and gene content in Fragaria, particularly among three octoploid strawberries which were F. × ananassa ‘Benihoppe’, F. chiloensis (GP33) and F. virginiana (O477). However, when the sequences of the coding and non-coding regions of F. × ananassa ‘Benihoppe’ were compared in detail with those of F. chiloensis (GP33) and F. virginiana (O477), a number of SNPs and InDels were revealed by MEGA 7. Six non-coding regions (trnK-matK, trnS-trnG, atpF-atpH, trnC-petN, trnT-psbD and trnP-psaJ) with a percentage of variable sites greater than 1% and no less than five parsimony-informative sites were identified and may be useful for phylogenetic analysis of the genus Fragaria.
Cheng et al. (2017) The complete chloroplast genome sequence of strawberry (Fragaria × ananassa Duch.) and comparison with related species of Rosaceae. PeerJ 5:e3919 https://doi.org/10.7717/peerj.3919