Novel ATG7::RAF1 gene fusion in malignant glomus tumor.

Glomus tumors are classified as members of the perivascular myoid family of tumors. Nearly half of these show NOTCH-gene fusions and a smaller subset has BRAF V600E mutations. Here, we report a novel ATG7::RAF1 fusion in malignant glomus tumor occurring in a 40-year-old female which has not been reported in the malignant glomus tumor before. A 40-year-old female presented with a persistent lateral heel pain and an increase in the size of a mass along the lateral ankle for nearly 10 years. Resected specimen showed a well circumscribed lesion composed of spindled and epithelioid cells with moderate nuclear atypia and mitotic figures (7/10 high-power fields) including atypical forms without any necrosis, lymphovascular, or perineural invasion. The tumor was positive for smooth muscle actin, smooth muscle myosin heavy chain, H-caldesmon, collagen type IV, and discovered on gastronintestinal stromal tumors-1 but negative for AE1/3, desmin, S-100, CD34, and CD117. RNA sequencing showed presence of ATG7-RAF1 fusion. This fusion has not been reported in the malignant glomus tumor before. Future studies on larger cohorts are needed to ascertain the biological significance of these tumors with novel gene fusions.

Clinicopathologic characteristics and follow up outcomes of invasive breast carcinoma with different positive HER2 fluorescence in situ hybridization patterns: experience from a single academic institution.

Human epidermal growth factor receptor 2 (HER2)-positive breast carcinoma (BC) encompasses a spectrum of molecular subtypes, characterized by varying HER2/CEP17 ratios and HER2 copy numbers, influencing responses to anti-HER2 therapy. This study stratified HER2 fluorescence in situ hybridization (FISH) positive patients into three distinct groups: Group 1 with high copy number (G1-HC: ratio ≥2, copy number ≥6), Group 1 with low copy number (G1-LC: ratio ≥2, copy number ≥4 and <6), and Group 3 (G3: ratio <2.0, copy number ≥6.0), and evaluated their clinicopathologic features, response to anti-HER2 therapy and outcomes. In a cohort of 2,702 continuous primary BCs, G1-HC BCs accounted for 304 cases (11.3%), G1-LC for 37 cases (1.4%) and G3 for 75 cases (2.8%). G1-HC BCs were associated with younger age, higher tumor grade, and estrogen receptor negativity compared to G1-LC BCs. Furthermore, G1-HC BCs exhibited increased progesterone receptor negativity and HER2 immunohistochemistry (IHC) 3+ compared to G1-LC and G3 BCs. Analysis of the subgroup of HER2 IHC 2+ only cases (n=166) showed similar results. Notably, G1-HC patients exhibited significantly enhanced responses to anti-HER2 neoadjuvant chemotherapy compared to G1-LC and G3 patients. Conversely, G1-LC patients displayed a lower likelihood of disease-free status compared to G1-HC and G3 patients, albeit with no significant differences in overall survival, distant metastasis, or local recurrence among the groups. These findings offer valuable clinicopathologic insights into different HER2 FISH positive subgroups, potentially informing future criteria for interpreting HER2 FISH results.

Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol.

AIMS: A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs. METHODS: Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL). RESULTS: Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm2 to 5.7 ± 2.5 cm2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R2 = 0.87, p = 0.03) and surface area (R2 = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX). CONCLUSION: In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.

Impact of coffee-derived chlorogenic acid on cognition: a systematic review and meta-analysis.

Coffee drinking has been associated with benefits for various health outcomes, with many attributed to the most prevalent family of polyphenols within coffee, chlorogenic acids (CGA). Whilst reviews of the association between coffee and cognition exist, evidence exploring effects of coffee-specific CGA on cognition has yet to be systematically synthesised. The purpose was to systematically review the current literature investigating the relationship between CGA from coffee and cognitive performance. A further objective was to undertake a meta-analysis of relevant randomised controlled trials (RCT). Observational and intervention studies were included if they considered coffee-based CGA consumption in human participants and applied a standardised measure of cognition. Furthermore, intervention studies were required to define the CGA content and include a control group/placebo. Studies were excluded if they examined CGA alone as an extract or supplement. A search of Scopus, PubMed, Web of Science, ScienceDirect and PsycINFO resulted in including twenty-three papers, six of which were interventions. The evidence from the broader systematic review suggests that CGA from coffee may need to be consumed chronically over a sustained period to produce cognitive benefits. However, the meta-analysis of RCT showed no benefits of coffee CGA intake on cognitive function (d = 0.00, 95% CI -0.05, 0.05). Overall, this review included a limited number of studies, the sample sizes were small, and a wide range of cognitive measures have been utilised. This indicates that further, good-quality interventions and RCT are required to systematically explore the conditions under which coffee CGA may provide benefits for cognitive outcomes.

Comprehensive molecular profile of primary cutaneous epithelioid rhabdomyosarcoma: A tumor genomically and molecularly related to malignant melanoma.

The histogenesis of the rare primary cutaneous epithelioid rhabdomyosarcoma (PCERMS) remains unclear, with the morphological and immunophenotypic appearance of a rhabdomyosarcoma but a genomic profile consistent with sarcomatoid undifferentiated malignant melanoma (SUMM). Here, we provide comprehensive clinical, histopathological, and genomic analysis of a putative PCERMS presenting in an elderly patient. Histopathologic examination revealed an ulcerative tumefactive lesion with diffuse replacement of the dermis by sheets of malignant epithelioid cells with a rhabdoid appearance. By immunohistochemistry, the tumor cells were strongly and diffusely positive for desmin and myogenin. Comprehensive genomic analysis with a 542 gene DNA-based sequencing panel revealed likely biallelic NF1 inactivation (mutation and deletion), TERT promoter mutation, and a high tumor mutation burden (>100 mutations/mB) with features of a UV-mutational signature, which are all genomic features that can be seen in undifferentiated malignant melanoma. This case provides evidence of a close relationship at a molecular level between PCERMS and SUMM. Molecular genomic characterization of a larger cohort of PCERMS is warranted for further elucidation.

Transcriptomic analysis implicates ABA signaling and carbon supply in the differential outgrowth of petunia axillary buds.

BACKGROUND: Shoot branching of flowering plants exhibits phenotypic plasticity and variability. This plasticity is determined by the activity of axillary meristems, which in turn is influenced by endogenous and exogenous cues such as nutrients and light. In many species, not all buds on the main shoot develop into branches despite favorable growing conditions. In petunia, basal axillary buds (buds 1-3) typically do not grow out to form branches, while more apical axillary buds (buds 6 and 7) are competent to grow. RESULTS: The genetic regulation of buds was explored using transcriptome analyses of petunia axillary buds at different positions on the main stem. To suppress or promote bud outgrowth, we grew the plants in media with differing phosphate (P) levels. Using RNA-seq, we found many (> 5000) differentially expressed genes between bud 6 or 7, and bud 2. In addition, more genes were differentially expressed when we transferred the plants from low P to high P medium, compared with shifting from high P to low P medium. Buds 6 and 7 had increased transcript abundance of cytokinin and auxin-related genes, whereas the basal non-growing buds (bud 2 and to a lesser extent bud 3) had higher expression of strigolactone, abscisic acid, and dormancy-related genes, suggesting the outgrowth of these basal buds was actively suppressed. Consistent with this, the expression of ABA associated genes decreased significantly in apical buds after stimulating growth by switching the medium from low P to high P. Furthermore, comparisons between our data and transcriptome data from other species suggest that the suppression of outgrowth of bud 2 was correlated with a limited supply of carbon to these axillary buds. Candidate genes that might repress bud outgrowth were identified by co-expression analysis. CONCLUSIONS: Plants need to balance growth of axillary buds into branches to fit with available resources while allowing some buds to remain dormant to grow after the loss of plant parts or in response to a change in environmental conditions. Here we demonstrate that different buds on the same plant with different developmental potentials have quite different transcriptome profiles.

Incidence, Clinicopathologic Features, HER2 Fluorescence In Situ Hybridization Profile, and Oncotype DX Results of Human Epidermal Growth Factor Receptor 2-Low Breast Cancers: Experience From a Single Academic Center.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer, defined by an immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization, is emerging as a predictive marker for the use of the antibody-drug conjugate. To understand how this category differs from HER2-zero cases, we investigated clinicopathological characteristics and HER2 fluorescence in situ hybridization results in a large cohort of 1309 continuous HER2-negative invasive breast carcinomas from 2018 to 2021 evaluated by the Food and Drug Administration-approved HER2 IHC test. Additionally, we compared Oncotype DX recurrence scores and HER2 mRNA expression between HER-low and HER2-zero cases in a separate cohort of 438 estrogen receptor-positive (ER+) early-stage breast carcinoma cases from 2014 to 2016. Based on the cohort from 2018 to 2021, the incidence of HER2-low breast cancers was approximately 54%. HER2-low cases had less frequent grade 3 morphology, less frequent triple-negative results, ER and progesterone receptor negativity, and a higher mean HER2 copy number and HER2/CEP17 ratio than HER2-zero cases (P < .0001). Among ER+ cases, HER2-low cases showed significantly less frequent Nottingham grade 3 tumors. In the cohort from 2014 to 2016, HER2-low cases showed significantly higher ER+ percentages, fewer progesterone receptor-negative cases, lower Oncotype DX recurrence scores, and higher HER2 mRNA expression scores than HER2-zero cases. In summary, this is the first study, to our knowledge, using a large cohort of continuous cases evaluated by the Food and Drug Administration-approved HER2 IHC companion diagnostic test for HER2-low expression and HER2 fluorescence in situ hybridization profile in a real-world setting. Although HER2-low cases showed a higher HER2 copy number, ratio, and mRNA level than HER2-zero cases statistically, such small differences are unlikely to be biologically or clinically meaningful. However, our study suggests that HER2-low/ER+ early-stage breast carcinoma may represent a less aggressive group of breast carcinoma, given its association with a lower Nottingham grade and Oncotype DX recurrence score.

Refining prognosis in chronic lymphocytic leukemia with normal Fluorescence in situ hybridization results.

Fluorescence in situ hybridization (FISH) to detect the recurrent cytogenetics abnormalities deletion 13q, trisomy 12, deletion 11q, and deletion 17p is important for prognostication in chronic lymphocytic leukemia (CLL). A subset of patients are negative for each of these abnormalities (normal 12/13/11/17 FISH), and outcomes are heterogenous within this group. To elucidate variables important for prognostication in this subgroup we conducted a retrospective analysis of 280 treatment-naïve CLL patients with normal standard CLL FISH results. In a multivariable model, advanced Rai stage (p = 0.04, hazard ratio [HR] 1.24 (95% confidence interval [CI] 1.01-1.53)), unmutated immunoglobulin heavy chain gene (IGHV) (p < 0.0001, HR 5.59 (95% CI 3.63-8.62)) and IGH rearrangement by FISH (p = 0.02, HR 2.56 (95% CI 1.20-5.48)) were significantly associated with shorter time to first treatment. In a multivariable model for overall survival, increasing age at 5-year increments (p < 0.0001, HR 1.55 (95% CI 1.25-1.93)), unmutated IGHV (p = 0.01, HR 5.28 (95% CI 1.52-18.35)) and gain of REL (p = 0.01, HR 4.08 (5% CI 1.45-11.49)) were significantly associated with shorter survival. Our study identifies variables important for refining prognosis for CLL patients with normal standard CLL FISH results.

Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia.

Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among ELN risk groups, with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate-, and adverse-risk groups, respectively (P < .001). A multivariate Cox model for OS using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.

Activation of the RAS pathway through uncommon BRAF mutations in mucinous pancreatic cysts without KRAS mutation.

Diagnostic testing of pancreatic cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has traditionally utilized elevated carcinoembryonic antigen (CEA) (≥192 ng/ml) and cytomorphologic examination to differentiate premalignant mucinous from benign pancreatic cystic lesions (PCLs). Molecular testing for KRAS/GNAS mutations has been shown to improve accuracy of detecting mucinous PCLs. Using a targeted next-generation sequencing (NGS) panel, we assess the status of PCL-associated mutations to improve understanding of the key diagnostic variables. Molecular analysis of cyst fluid was performed on 108 PCLs that had concurrent CEA and/or cytological analysis. A 48-gene NGS assay was utilized, which included genes commonly mutated in mucinous PCLs such as GNAS, KRAS, CDKN2A, and TP53. KRAS and/or GNAS mutations were seen in 59 of 68 (86.8%) cases with multimodality diagnosis of a mucinous PCL. Among 31 patients where surgical histopathology was available, the sensitivity, specificity, and diagnostic accuracy of NGS for the diagnosis of mucinous PCL was 88.5%, 100%, and 90.3%, respectively. Cytology with mucinous/atypical findings were found in only 29 of 62 cases (46.8%), with fluid CEA elevated in 33 of 58 cases (56.9%). Multiple KRAS mutations at different variant allele frequencies were seen in seven cases favoring multiclonal patterns, with six of them showing at least two separate PCLs by imaging. Among the 6 of 10 cases with GNAS + /KRAS- results, uncommon, non-V600E exon 11/15 hotspot BRAF mutations were identified. The expected high degree of accuracy of NGS detection of KRAS and/or GNAS mutations for mucinous-PCLs, as compared with CEA and cytological examination, was demonstrated. Multiple KRAS mutations correlated with multifocal cysts demonstrated by radiology. In IPMNs that lacked KRAS mutations, the concurring BRAF mutations with GNAS mutations supports an alternate mechanism of activation in the Ras pathway.

Red and blue light treatments of ripening bilberry fruits reveal differences in signalling through abscisic acid-regulated anthocyanin biosynthesis.

The biosynthesis of anthocyanins has been shown to be influenced by light quality. However, the molecular mechanisms underlying the light-mediated regulation of fruit anthocyanin biosynthesis are not well understood. In this study, we analysed the effects of supplemental red and blue light on the anthocyanin biosynthesis in non-climacteric bilberry (Vaccinium myrtillus L.). After 6 days of continuous irradiation during ripening, both red and blue light elevated concentration of anthocyanins, up to 12- and 4-folds, respectively, compared to the control. Transcriptomic analysis of ripening berries showed that both light treatments up-regulated all the major anthocyanin structural genes, the key regulatory MYB transcription factors and abscisic acid (ABA) biosynthetic genes. However, higher induction of specific genes of anthocyanin and delphinidin biosynthesis alongside ABA signal perception and metabolism were found in red light. The difference in red and blue light signalling was found in 9-cis-epoxycarotenoid dioxygenase (NCED), ABA receptor pyrabactin resistance-like (PYL) and catabolic ABA-8'hydroxylase gene expression. Red light also up-regulated expression of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) domain transporters, which may indicate involvement of these proteins in vesicular trafficking of anthocyanins during fruit ripening. Our results suggest differential signal transduction and transport mechanisms between red and blue light in ABA-regulated anthocyanin and delphinidin biosynthesis during bilberry fruit ripening.

Double somatic mismatch repair gene pathogenic variants as common as Lynch syndrome among endometrial cancer patients.

OBJECTIVE: Lynch syndrome is the most common cause of inherited endometrial cancer, attributable to germline pathogenic variants (PV) in mismatch repair (MMR) genes. Tumor microsatellite instability (MSI-high) and MMR IHC abnormalities are characteristics of Lynch syndrome. Double somatic MMR gene PV also cause MSI-high endometrial cancers. The aim of this study was to determine the relative frequency of Lynch syndrome and double somatic MMR PV. METHODS: 341 endometrial cancer patients enrolled in the Ohio Colorectal Cancer Prevention Initiative at The Ohio State University Comprehensive Cancer Center from 1/1/13-12/31/16. All tumors underwent immunohistochemical (IHC) staining for the four MMR proteins, MSI testing, and MLH1 methylation testing if the tumor was MMR-deficient (dMMR). Germline genetic testing for Lynch syndrome was undertaken for all cases with dMMR tumors lacking MLH1 methylation. Tumor sequencing followed if a germline MMR gene PV was not identified. RESULTS: Twenty-seven percent (91/341) of tumors were either MSI-high or had abnormal IHC indicating dMMR. As expected, most dMMR tumors had MLH1 methylation; (69, 75.8% of the dMMR cases; 20.2% of total). Among the 22 (6.5%) cases with dMMR not explained by methylation, 10 (2.9% of total) were found to have Lynch syndrome (6 MSH6, 3 MSH2, 1 PMS2). Double somatic MMR PV accounted for the remaining 12 dMMR cases (3.5% of total). CONCLUSIONS: Since double somatic MMR gene PV are as common as Lynch syndrome among endometrial cancer patients, paired tumor and germline testing for patients with non-methylated dMMR tumor may be the most efficient approach for LS screening.

Gliosarcoma with PNET features mimicking a metastatic neuroendocrine carcinoma: A diagnostic dilemma.

OBJECTIVE: Gliosarcomas (GS) comprise ~ 2 - 8% of glioblastomas and are associated with a similar poor prognosis. GS have rarely been found with a primitive neuroectodermal component (PNET). We present a case of gliosarcoma with PNET features (GS-PNET) that mimicked a neuroendocrine carcinoma on initial biopsy. MATERIALS AND METHODS: A 68-year-old male presented with 2 weeks of increasing headaches and difficulties with reading, writing, and word-finding. He was found to have a left-sided parieto-occipital heterogeneously enhancing mass. RESULTS: Pathologic analysis after surgical resection initially diagnosed a poorly differentiated carcinoma with neuroendocrine features, and adjuvant therapy was guided by this diagnosis as well as systemic imaging, which was suggestive of gastrointestinal primary malignancy with central nervous system (CNS) metastasis. Subsequent progression and re-resection established a diagnosis of GS with PNET component. Genomic profiling showed shared PTEN, TERT promotor, and TP53 mutations in the original and recurrent tumors. CONCLUSION: There have only been 5 previously reported cases of GS-PNET, to our knowledge, with this case representing the first with comprehensive molecular profiling. The case also highlights the importance of further work-up of presumed metastatic carcinoma with indeterminate immunostaining and/or suspected non-epithelioid component.

The school playground environment as a driver of primary school children's physical activity behaviour: A direct observation case study.

The school playground can promote PA for large numbers of children. This study identifies areas of the playground that children visited at break-times, the decisions according to gender and the influence of contextual and environmental variables on PA levels. The playground of a culturally diverse primary school was observed during morning break-times and lunchtimes. Counts of sedentary, LPA, and MVPA episodes, and the contexts in which they occurred were recorded using the system for observing play and leisure in youth (SOPLAY). Ball sports areas had higher counts of boys (mean ± SD; 9.9 ± 4.8) compared to girls (2.0 ± 3.5); areas promoting climbing and social interaction had higher counts of girls (7.9 ± 7.2) compared to boys (3.5 ± 2.9). The proportion of MVPA episodes during break-times was 34% ± 26%. Areas of the playground with organised activities had 2.70 (95%CI: 1.87 to 3.91) times higher MVPA counts than areas "not organised". Areas with "supervision" were associated with higher MVPA counts (1.34; 1.18 to 1.53) compared with "not supervised" areas. Organisation and supervision might influence PA choices and PA levels of children in the primary school playground. Further investigation is required to explore different playgrounds settings, and context and gender preferences.

" if I care about stuff, then other people care about me". Adolescents' experiences of helpful and unhelpful aspects of brief behavioural activation therapy for depression.

Brief Behavioural Activation (Brief BA) is a time limited psychological therapy for the treatment of depression symptoms in adolescents. Research on clients' experiences of the helpful and unhelpful aspects of psychological therapies is important for developing an understanding of the therapeutic process, and for helping to improve interventions and therapists' skills. The aim of this study was to explore 12-19 year old's experiences of the helpful and unhelpful aspects of Brief BA.Thematic analysis of one-to-one interviews with nine adolescents who had completed Brief BA at school was conducted.Three main themes relating to the helpful aspects were identified: "self-discovery"; "given the tools to cope and make progress"; "having someone to talk to." One main theme relating to the unhelpful aspects of Brief BA, "discontinuation and maintenance," was also identified.Findings indicated that the participants found behavioural activation strategies, identifying values and valued activities, and therapist support to be helpful. The duration of therapy and difficulties in maintaining improvements were identified as unhelpful aspects. Future research is needed to investigate the impact of the timing of the end of therapy and how improvements can be more easily maintained after the end of Brief BA.

Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Carbon starvation reduces carbohydrate and anthocyanin accumulation in red-fleshed fruit via trehalose 6-phosphate and MYB27.

Kiwifruit (Actinidia spp.) is a recently domesticated fruit crop with several novel-coloured cultivars being developed. Achieving uniform fruit flesh pigmentation in red genotypes is challenging. To investigate the cause of colour variation between fruits, we focused on a red-fleshed Actinidia chinensis var. chinensis genotype. It was hypothesized that carbohydrate supply could be responsible for this variation. Early in fruit development, we imposed high or low (carbon starvation) carbohydrate supplies treatments; carbohydrate import or redistribution was controlled by applying a girdle at the shoot base. Carbon starvation affected fruit development as well as anthocyanin and carbohydrate metabolite concentrations, including the signalling molecule trehalose 6-phosphate. RNA-Seq analysis showed down-regulation of both gene-encoding enzymes in the anthocyanin and carbohydrate biosynthetic pathways. The catalytic trehalose 6-phosphate synthase gene TPS1.1a was down-regulated, whereas putative regulatory TPS7 and TPS11 were strongly up-regulated. Unexpectedly, under carbon starvation MYB10, the anthocyanin pathway regulatory activator was slightly up-regulated, whereas MYB27 was also up-regulated and acts as a repressor. To link these two metabolic pathways, we propose a model where trehalose 6-phosphate and the active repressor MYB27 are involved in sensing the carbon starvation status. This signals the plant to save resources and reduce the production of anthocyanin in fruits.

Whole Genome Sequence Resource of the Asian Pear Scab Pathogen Venturia nashicola.

Venturia nashicola, the cause of scab disease of Asian pears, is a host-specific, biotrophic fungus. It is restricted to Asia and is regarded as a quarantine threat outside this region. European pear displays nonhost resistance (NHR) to V. nashicola and Asian pears are nonhosts of V. pyrina (the cause of European pear scab disease). The host specificity of these two fungi is likely governed by differences in their effector arsenals, with a subset hypothesized to activate NHR. The Pyrus-Venturia pathosystem provides an opportunity to dissect the underlying genetics of nonhost interactions in this potentially more durable form of resistance. The V. nashicola genome will enable comparisons to other Venturia spp. genomes to identify effectors that potentially activate NHR in the pear scab pathosystem.

Response to 'The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement' by Cumming et al.

Please see related article: https://doi.org/10.1186/s12916-019-1410-x.