Targeting the immune checkpoint pathway has demonstrated antitumor cytotoxicity in treatment-refractory head and neck squamous cell carcinoma (HNSC). To understand the molecular mechanisms ...underpinning its antitumor response, we characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups.
A training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. We separated gene expression patterns from tumor, stromal, and immune cell gene using a non-negative matrix factorization algorithm. We correlated the expression patterns with a set of immune-related gene signatures, potential immune biomarkers, and clinicopathological features. Six independent datasets containing 838 HNSC samples were used for validation.
Approximately 40% of HNSCs in the cohort (211/522) were identified to show enriched inflammatory response, enhanced cytolytic activity, and active interferon-γ signaling (all, P < 0.001). We named this new molecular class of tumors the Immune Class. Then we found it contained two distinct microenvironment-based subtypes, characterized by markers of active or exhausted immune response. The Exhausted Immune Class was characterized by enrichment of activated stroma and anti-inflammatory M2 macrophage signatures, WNT/transforming growth factor-β signaling pathway activation and poor survival (all, P < 0.05). An enriched proinflammatory M1 macrophage signature, enhanced cytolytic activity, abundant tumor-infiltrating lymphocytes, high human papillomavirus (HPV) infection, and favorable prognosis were associated with Active Immune Class (all, P < 0.05). The robustness of these immune molecular subgroups was verified in the validation cohorts, and Active Immune Class showed potential response to programmed cell death-1 blockade (P = 0.01).
This study revealed a novel Immune Class in HNSC; two subclasses characterized by active or exhausted immune responses were also identified. These findings provide new insights into tailoring immunotherapeutic strategies for different HNSC subgroups.
Families and genera assigned to Tremellomycetes have been mainly circumscribed by morphology and for the yeasts also by biochemical and physiological characteristics. This phenotype-based ...classification is largely in conflict with molecular phylogenetic analyses. Here a phylogenetic classification framework for the Tremellomycetes is proposed based on the results of phylogenetic analyses from a seven-genes dataset covering the majority of tremellomycetous yeasts and closely related filamentous taxa. Circumscriptions of the taxonomic units at the order, family and genus levels recognised were quantitatively assessed using the phylogenetic rank boundary optimisation (PRBO) and modified general mixed Yule coalescent (GMYC) tests. In addition, a comprehensive phylogenetic analysis on an expanded LSU rRNA (D1/D2 domains) gene sequence dataset covering as many as available teleomorphic and filamentous taxa within Tremellomycetes was performed to investigate the relationships between yeasts and filamentous taxa and to examine the stability of undersampled clades. Based on the results inferred from molecular data and morphological and physiochemical features, we propose an updated classification for the Tremellomycetes. We accept five orders, 17 families and 54 genera, including seven new families and 18 new genera. In addition, seven families and 17 genera are emended and one new species name and 185 new combinations are proposed. We propose to use the term pro tempore or pro tem. in abbreviation to indicate the species names that are temporarily maintained.
Most small genera containing yeast species in the Pucciniomycotina (Basidiomycota, Fungi) are monophyletic, whereas larger genera including Bensingtonia, Rhodosporidium, Rhodotorula, Sporidiobolus ...and Sporobolomyces are polyphyletic. With the implementation of the “One Fungus = One Name” nomenclatural principle these polyphyletic genera were revised. Nine genera, namely Bannoa, Cystobasidiopsis, Colacogloea, Kondoa, Erythrobasidium, Rhodotorula, Sporobolomyces, Sakaguchia and Sterigmatomyces, were emended to include anamorphic and teleomorphic species based on the results obtained by a multi-gene phylogenetic analysis, phylogenetic network analyses, branch length-based methods, as well as morphological, physiological and biochemical comparisons. A new class Spiculogloeomycetes is proposed to accommodate the order Spiculogloeales. The new families Buckleyzymaceae with Buckleyzyma gen. nov., Chrysozymaceae with Chrysozyma gen. nov., Microsporomycetaceae with Microsporomyces gen. nov., Ruineniaceae with Ruinenia gen. nov., Symmetrosporaceae with Symmetrospora gen. nov., Colacogloeaceae and Sakaguchiaceae are proposed. The new genera Bannozyma, Buckleyzyma, Fellozyma, Hamamotoa, Hasegawazyma, Jianyunia, Rhodosporidiobolus, Oberwinklerozyma, Phenoliferia, Pseudobensingtonia, Pseudohyphozyma, Sampaiozyma, Slooffia, Spencerozyma, Trigonosporomyces, Udeniozyma, Vonarxula, Yamadamyces and Yunzhangia are proposed to accommodate species segregated from the genera Bensingtonia, Rhodosporidium, Rhodotorula, Sporidiobolus and Sporobolomyces. Ballistosporomyces is emended and reintroduced to include three Sporobolomyces species of the sasicola clade. A total of 111 new combinations are proposed in this study.
The subphylum Ustilaginomycotina (Basidiomycota, Fungi) comprises mainly plant pathogenic fungi (smuts). Some of the lineages possess cultivable unicellular stages that are usually classified as ...yeast or yeast-like species in a largely artificial taxonomic system which is independent from and largely incompatible with that of the smut fungi. Here we performed phylogenetic analyses based on seven genes including three nuclear ribosomal RNA genes and four protein coding genes to address the molecular phylogeny of the ustilaginomycetous yeast species and their filamentous counterparts. Taxonomic revisions were proposed to reflect this phylogeny and to implement the ‘One Fungus = One Name’ principle. The results confirmed that the yeast-containing classes Malasseziomycetes, Moniliellomycetes and Ustilaginomycetes are monophyletic, whereas Exobasidiomycetes in the current sense remains paraphyletic. Four new genera, namely Dirkmeia gen. nov., Kalmanozyma gen. nov., Golubevia gen. nov. and Robbauera gen. nov. are proposed to accommodate Pseudozyma and Tilletiopsis species that are distinct from the other smut taxa and belong to clades that are separate from those containing type species of the hitherto described genera. Accordingly, new orders Golubeviales ord. nov. with Golubeviaceae fam. nov. and Robbauerales ord. nov. with Robbaueraceae fam. nov. are proposed to accommodate the sisterhood of Golubevia gen. nov. and Robbauera gen. nov. with other orders of Exobasidiomycetes. The majority of the remaining anamorphic yeast species are transferred to corresponding teleomorphic genera based on strongly supported phylogenetic affinities, resulting in the proposal of 28 new combinations. The taxonomic status of a few Pseudozyma species remains to be determined because of their uncertain phylogenetic positions. We propose to use the term pro tempore or pro tem. in abbreviation to indicate the single-species lineages that are temporarily maintained.
Summary
Background
TCS (topical corticosteroids) are the first‐line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, ...pimecrolimus and ciclosporin for OLP is still controversial.
Objectives
To compare the efficacy and safety of TCI vs. TCS for OLP.
Methods
The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events.
Results
Twenty‐one trials involving 965 patients were included in the analysis. For the treatment of OLP (3–8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus–TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short‐term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious.
Conclusions
The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short‐term treatment in recalcitrant OLP. Further well‐designed trials are warranted to evaluate the long‐term efficacy and safety of TCI.
What's already known about this topic?
The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS).
Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs.
Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune‐mediated diseases.
What does this study add?
TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short‐term treatment of OLP.
The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious.
The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short‐term and long‐term efficacy and safety of TCI compared with TCS.
Linked Comment: Thongprasom. Br J Dermatol 2019; 181:1120.
Plain language summary available online
The Tremellomycetes (Basidiomycota) contains a large number of unicellular and dimorphic fungi with stable free-living unicellular states in their life cycles. These fungi have been conventionally ...classified as basidiomycetous yeasts based on physiological and biochemical characteristics. Many currently recognised genera of these yeasts are mainly defined based on phenotypical characters and are highly polyphyletic. Here we reconstructed the phylogeny of the majority of described anamorphic and teleomorphic tremellomycetous yeasts using Bayesian inference, maximum likelihood, and neighbour-joining analyses based on the sequences of seven genes, including three rRNA genes, namely the small subunit of the ribosomal DNA (rDNA), D1/D2 domains of the large subunit rDNA, and the internal transcribed spacer regions (ITS 1 and 2) of rDNA including 5.8S rDNA; and four protein-coding genes, namely the two subunits of the RNA polymerase II (RPB1 and RPB2), the translation elongation factor 1-α (TEF1) and the mitochondrial gene cytochrome b (CYTB). With the consideration of morphological, physiological and chemotaxonomic characters and the congruence of phylogenies inferred from analyses using different algorithms based on different data sets consisting of the combined seven genes, the three rRNA genes, and the individual protein-coding genes, five major lineages corresponding to the orders Cystofilobasidiales, Filobasidiales, Holtermanniales, Tremellales, and Trichosporonales were resolved. A total of 45 strongly supported monophyletic clades with multiple species and 23 single species clades were recognised. This phylogenetic framework will be the basis for the proposal of an updated taxonomic system of tremellomycetous yeasts that will be compatible with the current taxonomic system of filamentous basidiomycetes accommodating the ‘one fungus, one name’ principle.
Summary Objective Dietary loading has been reported to have an effect on temporomandibular joint (TMJ) remodeling via periodontal-muscular reflex. We therefore examined whether reducing dietary ...loading decreased TMJ degradation induced by the unilateral anterior crossbite prosthesis as we recently reported. Methods Forty 6-week-old female C57BL/6J mice were randomly divided into two experimental and two control groups. One experimental and one control group received small-size diet and the other two groups received large-size diet. Unilateral anterior crossbite prosthesis was created in the two experimental groups. The TMJ samples were collected 3 weeks after experimental operation. Histological changes in condylar cartilage and subchondral bone were assessed by Hematoxylin & Eosin, toluidine blue, Safranin O and tartrate-resistant acid phosphatase staining. Real-time polymerase chain reaction (PCR) and/or immunohistochemistry were performed to evaluate the expression levels of Collagen II, Aggrecan, a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) and RANKL/RANK/OPG in TMJ condylar cartilage and/or subchondral bone. Results Thinner and degraded cartilage, reduced cartilage cellular density, decreased expression levels of Collagen II and Aggrecan, loss of subchondral bone and enhanced osteoclast activity were observed in TMJs of both experimental groups. However, the cartilage degradation phenotype was less severe and cartilage ADAMTS-5 mRNA was lower while OPG/RANKL ratio in cartilage and subchondral bone was higher in the small-size than large-size diet experimental group. No differences of histomorphology and the tested molecules were found between the two control groups. Conclusions The current findings suggest that a lower level of functional loading by providing small-size diet could reduce TMJ degradation induced by the biomechanical stimulation from abnormal occlusion.
was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of
and
in China and has subsequently been identified worldwide in various species of the family
...encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in
Here, we investigated the effects of
on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (
,
,
,
,
, and
species) pathogens, which are often treated clinically by colistin. The effects of
on colistin resistance were determined using MIC assays of laboratory and clinical strains of
,
,
, and
Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of
led to colistin resistance in
,
, and
but only moderately reduced susceptibility in
Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of
expression among ESKAPE pathogens, especially in
and
Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of
or plasmid-mediated phosphoethanolamine transferases in general.
Background
Acupuncture is used to treat chronic functional constipation (CFC) in China, despite limited evidence. We aim to assess the effectiveness and safety of acupuncture in managing CFC.
Methods
...A multicenter randomized controlled trial was performed involving 684 patients with CFC; the patients were randomly allocated to receive He acupuncture (n = 172), Shu‐mu acupuncture (n = 171), He‐shu‐mu acupuncture (n = 171), or oral administration of mosapride (n = 170). Sixteen sessions of acupuncture were given in the treatment duration of 4 weeks. The primary outcome was the change in spontaneous bowel movements (SBMs) at week 4 (at the end of treatment) compared to baseline. The secondary outcomes included stool consistency (Bristol scale), the degree of straining during defecation, and adverse events.
Key Results
The SBMs increased in all the four groups at week 4, and the magnitude of increase was equivalent in the four groups (He acupuncture, 2.7 95% CI, 2.3‐3.1; Shu‐mu acupuncture, 2.7 95% CI, 2.3‐3.0; He‐shu‐mu acupuncture, 2.2 95% CI, 1.9‐2.5; and mosapride, 2.4 95% CI, 2.0‐2.9; P = .226). However, the change in SBMs at week 8 was significantly smaller in mosapride group (1.4 95% CI, 1.0‐1.8) than the three acupuncture groups (2.4 95% CI, 2.1‐2.7, 2.3 95% CI, 1.9‐2.7, 2.1 95% CI, 1.7‐2.5 in He, Shu‐mu, and He‐shu‐mu group, respectively, P = .005).
Conclusions & Interferences
The three acupuncture treatments were as effective as mosapride in improving stool frequency and stool consistency in CFC, but the magnitude of the treatment effect is unknown due to the lack of sham acupuncture control.
The effectiveness of acupuncture in the treatment of chronic functional constipation is unknown. Our study result showed that acupuncture treatments are as effective as mosapride in improving stool frequency and stool consistency.
Aim To evaluate the amplitude of low-frequency oscillations (LFOs) of the brain in migraine patients using amplitude of low-frequency fluctuation (ALFF) and fractional ALFF in the interictal period, ...in comparison to healthy controls (HCs). Materials and methods A total of 54 subjects, including 30 migraineurs and 24 gender- and age-matched HCs completed the fMRI. All the data and ALFF, fALFF analyses were preprocessed with the Data Processing Assistant for Resting-State fMRI (DPARSF). All of the statistical analyses were performed using the REST software to explore the differences in ALFF and fALFF between migraine patients and HCs. Results In contrast to HCs, migraine patients showed significant ALFF increase in the left medulla and pons, the bilateral cerebellum posterior lobe and right insula. The regions showing decreased ALFF in migraine patients included the bilateral cerebellum posterior lobe, left cerebellum anterior lobe, bilateral orbital cortex, right middle frontal gyrus, bilateral occipital lobe, right fusiform gyrus, and bilateral postcentral gyrus. The fALFFs in migraine patients were significantly increased in the bilateral insular and left orbital cortex, but were decreased in the left occipital lobe and bilateral cerebellum posterior lobe. Conclusion These ALFF and fALFF alterations in the brain regions of migraineurs are in keeping with the domains associated with pain and cognition. Such brain functional alteration may contribute to further understanding of migraine-related network imbalances demonstrated in previous studies.