Miracle-dz/UniFAR-FTUs huggingface dataset:
The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants

Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous DNMT3A variants. Here we have undertaken a detailed clinical study of 55 individuals with de novo DNMT3A variants, including the 13 previously reported individuals. An intellectual disability and overgrowth were reported in >80% of individuals with TBRS and were designated major clinical associations. Additional frequent clinical associations (reported in 20-80% individuals) included an evolving facial appearance with low-set, heavy, horizontal eyebrows and prominent upper central incisors; joint hypermobility (74%); obesity (weight ³2SD, 67%); hypotonia (54%); behavioural/psychiatric issues (most frequently autistic spectrum disorder, 51%); kyphoscoliosis (33%) and afebrile seizures (22%). One individual was diagnosed with acute myeloid leukaemia in teenage years. Based upon the results from this study, we present our current management for individuals with TBRS
Unravelling Colletotrichum species associated with Camellia: employing ApMat and GS loci to resolve species in the C. gloeosporioides complex

We investigated the phylogenetic diversity of 144 Colletotrichum isolates associated with symptomatic and asymptomatic tissues of Camellia sinensis and other Camellia spp. from seven provinces in China (Fujian, Guizhou, Henan, Jiangxi, Sichuan, Yunnan, Zhejiang), and seven isolates obtained from other countries, including Indonesia, UK, and the USA. Based on multi-locus (ACT, ApMat, CAL, GAPDH, GS, ITS, TUB2) phylogenetic analyses and phenotypic characters, 11 species were distinguished, including nine well-characterised species (C. alienum, C. boninense, C. camelliae, C. cliviae, C. fioriniae, C. fructicola, C. gloeosporioides, C. karstii, C. sia-mense), and two novel species (C. henanense and C. jiangxiense). Of these, C. camelliae proved to be the most dominant and probably host specific taxon occurring on Camellia. An epitype is also designated for the latter species in this study. Colletotrichum jiangxiense is shown to be phylogenetically closely related to the coffee berry pathogen C. kahawae subsp. kahawae. Pathogenicity tests and the pairwise homoplasy index test suggest that C. jiangxiense and C. kahawae subsp. kahawae are two independent species. This study represents the first report of C. alienum and C. cliviae occurring on Camellia sinensis. In addition, our study demonstrated that the combined use of the loci ApMat and GS in a phylogenetic analysis is able to resolve all currently accepted species in the C. gloeosporioides species complex.
Antifungal Susceptibility Testing of Dermatophytes by Agar Based Disk Diffusion Assay in Tertiary Care Hospital, Nepal

Background: Dermatophytes are fungi, which cause most of superficial fungal infections. Several antifungal agents are commercially available to treat these dermatophytes. Methods: We adopted a newly developed agar based disk diffusion assay to test susceptibility of 72 clinically isolated dermatophytes belonging to 5 species Trichophyton interdigitale (44), Trichophtyon rubrum (13), Trichophyton tonsurans (6), Microsporum canis (6), and Epidermatophyton floccosum (3). The process involved the application of four commercially available anti-fungal disks namely Ketoconazole (15 μg), Miconazole (10 μg), Fluconazole (25 μg) and Clotrimazole (10 μg) for antifungal susceptibility testing. Results: The study shows miconazole is the most effective antifungal drugs against dermatophytes followed by ketoconazole and clotrimozazole. Original Research Article Khadka et al.; MRJI, 19(2): 1-5, 2017; Article no.MRJI. 31827 2 Conclusions: The disk diffusion assay method for antifungal susceptibility testing of dermatophytes species in this in vitro study may give insights into the application in therapeutic strategy against dermatophytic infections. Disk diffusion method is a simple and cost-effective for susceptibility testing of dermatophytes.
Associations between Living Near Water and Risk of Mortality among Urban Canadians

Background: Increasing evidence suggests that residential exposures to natural environments, such as green spaces, are associated with many health benefits. Only a single study has examined the potential link between living near water and mortality. Objective: We sought to examine whether residential proximity to large, natural water features (e.g., lakes, rivers, coasts, “blue space”) was associated with cause-specific mortality. Methods: Our study is based on a population-based cohort of nonimmigrant adults living in the 30 largest Canadian cities [i.e., the 2001 Canadian Census Health and Environment Cohort) (CanCHEC)]. Subjects were drawn from the mandatory 2001 Statistics Canada long-form census, who were linked to the Canadian mortality database and to annual income-tax filings, through 2011. We estimated associations between living within 250m of blue space and deaths from several common causes of death. We adjusted models for many personal and contextual covariates, as well as for exposures to residential greenness and ambient air pollution. Results: Our cohort included approximately 1.3 million subjects at baseline, 106,180 of whom died from nonaccidental causes during follow-up. We found significant, reduced risks of mortality in the range of 12–17% associated with living within 250m of water in comparison with living farther away, among all causes of death examined, except with external/accidental causes. Protective effects were found to be higher among women and all older adults than among other subjects, and protective effects were found to be highest against deaths from stroke and respiratory-related causes. Conclusions: Our findings suggest that living near blue spaces in urban areas has important benefits to health, but further work is needed to better understand the drivers of this association. https://doi.org/10.1289/EHP3397
Elevated expression of Tiam1 is associated with poor prognosis and promotes tumor progression in pancreatic cancer

Objective: T-cell lymphoma invasion and metastasis inducing factor 1 (Tiam1) is known to be involved in tumor progression. However, its molecular roles and mechanism in pancreatic ductal adenocarcinoma (PDAC) remain unclear. The purpose of this study is to determine Tiam1 expression levels and investigate its underlying molecular mechanism in PDAC. Materials and methods: Tiam1 protein expression levels in PDAC tissues were examined using immunohistochemistry. Tiam1 expression was confirmed in pancreatic cancer (PC) cells by Western blot and immunofluorescence staining. Tiam1-silenced PC cells were created using short interfering RNA. Subsequently, colony formation, scratch, and migration and invasion assays were carried out to explore the molecular mechanisms of Tiam1 in PC cells. Results: The results indicated that Tiam1 expression was significantly higher in PDAC tissues than in paired non-tumor tissues, and overexpression of Tiam1 was significantly correlated with histological grade ( P = 0.040) and lymph node metastasis ( P = 0.031) in PDAC. The PDAC patients with high Tiam1 expression had significantly lower 5-year overall survival than patients with low Tiam1 expression. More importantly, univariate and multivariate analysis suggested that Tiam1 expression, along with lymph node metastasis, is a significant independent prognostic factor for patients with PDAC. Furthermore, we also demonstrated that the downregulation of Tiam1 was associated with decreased cell proliferation and reduced migratory and invasive capability. Conclusion: High expression of Tiam1 plays a significant role in the progression of PDAC and may be a potential biomarker of poor prognosis as well as a therapeutic target.
Maternal postnatal depression and anxiety and their association with child emotional negativity and behavior problems at two years

Prenoveau, J. M. , Craske, M. G. , West, V. , Giannakakis, A. , Zioga, M. , Lehtonen, A. , Davies, B. , Netsi, E. , Cardy, J., Cooper, P., Murray, L. and Stein, A. (2017) Maternal postnatal depression and anxiety and their association with child emotional negativity and behavior problems at two years. Developmental Psychology, 53 (1). pp. 50­62. ISSN 0012­1649 doi: https://doi.org/10.1037/dev0000221 Available at http://centaur.reading. ac.uk/68609/
Neuronal connectivity in major depressive disorder: a systematic review

Background: The causes of major depressive disorder (MDD), as one of the most common psychiatric disorders, still remain unclear. Neuroimaging has substantially contributed to understanding the putative neuronal mechanisms underlying depressed mood and motivational as well as cognitive impairments in depressed individuals. In particular, analyses addressing changes in interregional connectivity seem to be a promising approach to capture the effects of MDD at a systems level. However, a plethora of different, sometimes contradicting results have been published so far, making general conclusions difficult. Here we provide a systematic overview about connectivity studies published in the field over the last decade considering different methodological as well as clinical issues. Methods: A systematic review was conducted extracting neuronal connectivity results from studies published between 2002 and 2015. The findings were summarized in tables and were graphically visualized. Results: The review supports and summarizes the notion of an altered fronto-limbic mood regulation circuitry in MDD patients, but also stresses the heterogeneity of the findings. The brain regions that are most consistently affected across studies are the orbitomedial prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, cerebellum and the basal ganglia. Conclusion: The results on connectivity in MDD are very heterogeneous, partly due to different methods and study designs, but also due to the temporal dynamics of connectivity. While connectivity research is an important step toward a complex systems approach to brain functioning, future research should focus on the dynamics of functional and effective connectivity. parahippocampus; PST, pallido-striatum; sACC, subgenual SFG, SMG, STG, superior temporal STP, superior pole; depression; TSD, depression; PFC; vMePFC, ventromedial PFC; vRP, ventral rostral putamen; ventral striatum. precuneus; PFC, prefrontal cortex; precentral gyrus; PHG, parahippocampus; PST, pallidostriatum; RPFC, rostral PFC; S1/M1, primary sensorimotor cortex; SFG, superior frontal gyrus; SMA, suppl. motor area; SOG, superior occipital gyrus; SPFC, superior PFC; SPG, superior parietal gyrus; STG, superior temporal gyrus; subACC, subgenual vCN, ventral CN; vLPFC, ventrolateral PFC; vMePFC, ventromedial PFC; vs, ventral striatum.
Indonesia’s forest moratorium: A stepping stone to better forest governance?

On 20 May 2011, the government of Indonesia released Presidential Instruction No. 10/2011 on ‘The postponement of issuance of new licences and improving governance of primary natural forest and peatland', as part of Indonesia's cooperation with the government of the Kingdom of Norway, according to the Letter of Intent signed by the two governments on 26 May 2010. The Presidential Instruction, which effectively imposes a 2-year moratorium on new forest concession licences, generated widespread public discourse and important policy implications. This working paper analyses the significance of the moratorium in the context of improving forest governance in Indonesia. The moratorium on new concessions in forest areas is an important step towards meeting Indonesia's voluntary commitment to reduce emissions. However, several issues are unresolved concerning the area and status of land covered by the moratorium, and hence the amount of carbon stored in the affected forests and peatlands. The moratorium should be seen as the means and breathing space to establish enabling conditions to reduce greenhouse gases emissions, improve forest and peatland governance, for when a global mechanism such as REDD+ is fully implemented. It could pave the way for successful policy reform far beyond its 2-year term.
Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase

Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome. Mpp6-exosomes can recruit Mtr4, while Mpp6 and Rrp47 each contribute to Mtr4-dependent RNA decay, with maximal Mtr4-dependent decay observed with both cofactors. The 3.3 Å structure of a twelve-subunit nuclear Mpp6 exosome bound to RNA shows the central region of Mpp6 bound to the exosome core, positioning its Mtr4 recruitment domain next to Rrp6 and the exosome central channel. Genetic analysis reveals interactions that are largely consistent with our model. DOI: http://dx.doi. org/10.7554/eLife.29062. 001
Mitochondrial Biogenesis in Diverse Cauliflower 2 Cultivars under Mild and Severe Drought Involves 3 Impaired Coordination of Transcriptomic and 4 Proteomic Response and Regulation of Various 5 Multifunctional Proteins 6

The early generative phase of cauliflower (Brassica oleracea var. botrytis) curd ripening is 21 sensitive to the water deficit. Mitochondrial responses under drought within Brassica genus are 22 poorly understood. The main goal of this study was to investigate the mitochondrial biogenesis of 23 three cauliflower cultivars varying with drought tolerance. Diverse quantitative changes 24 (down-regulations mostly) in the mitochondrial proteome were assayed by 2D PAGE coupled with 25 LC-MS/MS. Respiratory (e.g. CII, CIV and ATP synthase subunits), transporter (including diverse 26 porin isoforms) and matrix multifunctional proteins (e.g. components of RNA editing machinery) 27 appeared diversely affected in their abundance under two drought levels. Western immunoassays 28 showed also cultivar-specific responses of selected mitochondrial proteins. Dehydrin-related 29 tryptic peptides found in few 2D spots that appeared immunopositive with dehydrin-specific 30 antisera highlighted the relevance of mitochondrial dehydrin-like proteins for the drought 31 response. The level of selected messengers participating in drought response was also determined. 32 We conclude that the mitochondrial biogenesis was strongly, but diversely affected in various 33 cauliflower cultivars and associated with drought tolerance on the proteomic and functional levels. 34 However, transcriptomic and proteomic regulations were largely uncoordinated due to the 35 suggested altered availability of messengers for translation, mRNA/ribosome interactions and/or 36 miRNA impact on transcript abundance and translation. 37
Clinical Characteristics and Factors Associated With Long-Term Viral Excretion in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Single-Center 28-Day Study

Abstract Background Despite the ongoing spread of coronavirus disease 2019 (COVID-19), knowledge about factors affecting prolonged viral excretion is limited. Methods In this study, we retrospectively collected data from 99 hospitalized patients with coronavirus disease 2019 (COVID-19) between 19 January and 17 February 2020 in Zhejiang Province, China. We classified them into 2 groups based on whether the virus test results eventually became negative. Cox proportional hazards regression was used to evaluate factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding. Results Among 99 patients, 61 patients had SARS-CoV-2 clearance (virus-negative group), but 38 patients had sustained positive results (virus-positive group). The median duration of SARS-CoV-2 excretion was 15 (interquartile range, 12–19) days among the virus-negative patients. The shedding time was significantly increased if the fecal SARS-CoV-2 RNA test result was positive. Male sex (hazard ratio [HR], 0.58 [95% confidence interval {CI}, .35–.98]), immunoglobulin use (HR, 0.42 [95% CI, .24–.76]), APACHE II score (HR, 0.89 [95% CI, .84–.96]), and lymphocyte count (HR, 1.81 [95% CI, 1.05–3.1]) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. Antiviral therapy and corticosteroid treatment were not independent factors. Conclusions SARS-CoV-2 RNA clearance time was associated with sex, disease severity, and lymphocyte function. The current antiviral protocol and low-to-moderate dosage of corticosteroid had little effect on the duration of viral excretion.
ICESat full waveform signal analysis for the classification of land cover types over the cryosphere

The Earth needs attention. That is the bottom line of today’s discussion on the impact of humans on the environment and their contribution to global warming. With the rapid sea level rise and the melting ice caps, it is becoming increasingly important to understand these processes. Mass balance estimates of the cryosphere (e.g. Greenland and Antarctica) are one of the keys to unlocking the secrets of today’s concerns and predicting tomorrow’s problems. The primary objective of this research is to construct an automatic classification algorithm to that will distinguish between the polar land cover types: ice, rock, snow and water. The algorithm is based on full waveform laser altimetry measurements gathered by the Ice, Cloud and Elevation Satellite (ICESat). The results of this research have the potential to play an important role in improving the current methods for computing mass balance estimates and monitoring seasonal changes in land cover type of the cryosphere.
Towards High-Quality Specular Highlight Removal by Leveraging Large-Scale Synthetic Data

This paper aims to remove specular highlights from a single object-level image. Although previous methods have made some progresses, their performance remains somewhat limited, particularly for real images with complex specular highlights. To this end, we propose a three-stage network to address them. Specifically, given an input image, we first decompose it into the albedo, shading, and specular residue components to estimate a coarse specular-free image. Then, we further refine the coarse result to alleviate its visual artifacts such as color distortion. Finally, we adjust the tone of the refined result to match the tone of the input as closely as possible. In addition, to facilitate network training and quantitative evaluation, we present a large-scale synthetic dataset of object-level images, covering diverse objects and illumination conditions. Extensive experiments illustrate that our network is able to generalize well to unseen real object-level images, and even produce good results for scene-level images with multiple background objects and complex lighting.
The involvement of Kras gene 3 ′ -UTr polymorphisms in risk of cancer and influence on patient response to anti-egFr therapy in metastatic colorectal cancer: a meta-analysis

Background: Genetic variation of the Kras oncogene is a candidate factor for increasing susceptibility to carcinoma and modulating response of metastatic colorectal cancer (mCRC) patients treated with anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR). However, results from an increasing number of studies concerning the association of Kras gene rs712 and rs61764370 polymorphisms with risk of cancer and treatment of mCRC using anti-EGFR remain equivocal. Methods: Risk associations were evaluated in 1,661 cases and 2,139 controls from six studies concerning rs712 and 14,796 cases and 14,985 controls from 29 studies concerning rs61764370. Response association was also examined in a subset of four studies pertaining to rs61764370 and anti-EGFR treatment in mCRC. Results: Results of a meta-analysis showed that allele T ( P -value of heterogeneity test [ P H ] = 0.08, odds ratio [OR] = 1.33, 95% confidence interval [CI]: 1.08–1.64) and genotype GT/TT ( P H = 0.14, OR = 1.30, 95% CI: 1.10–1.55) in rs712 were strongly associated with cancer in Chinese sub-jects. No evidence of association was observed between rs712 and risk of cancer in the overall population or between rs61764370 and ovarian, breast, colorectal, or non-small-cell lung cancer risk in the Caucasian population. No significant association was found between rs61764370 and patient response to anti-EGFR therapy in mCRC. Conclusion: The findings not only provide further evidence that allele T of rs712 increases genetic predisposition to cancer in Chinese population, but also no significant association between rs61764370 and cancer risk in Caucasian population, and suggest that genotype GT/ TT of rs61764370 may not be a biomarker for predicting clinical outcome of anti-EGFR therapy in mCRC.
Trade Policy Uncertainty and Shareholder Returns in Mergers and Acquisitions

We use a change in US trade policy, which eliminated uncertainty regarding potential tariﬀ increases on Chinese imports, to examine the eﬀect of resolution of trade policy uncertainty on merger and acquisition (M&A) activity and shareholder value of acquiring and target ﬁrms. After this policy change, industries with greater resolution of tariﬀ uncertainty experience higher within-industry and cross-industry M&A activity, and acquiring ﬁrms in these industries experience higher announcement returns, but there is no corresponding eﬀect on target announcement returns. Acquirer shareholder wealth eﬀects are stronger for R&D-intensive acquirers; in transactions involving publicly-traded targets, especially for less proﬁtable and high-leverage targets; and for cross-industry acquisitions, especially those in which the target is in a less competitive and less ﬂuid product market than the acquirer. The eﬀects on acquirer shareholder wealth indicate that elimination of trade policy uncertainty and increase in import competition raise the bargaining power of acquirers relative to targets.
effects of creative expression therapy for older adults with mild cognitive impairment at risk of Alzheimer’s disease: a randomized controlled clinical trial

Objective: Elderly people with mild cognitive impairment (MCI) are at high risk for dementia. This study compared the effects of standard cognitive training with a creative expression (CrExp) program. Methods: Adult patients with MCI aged 60 years and older (N = 93) were randomly assigned to either CrExp therapy (n = 48) or a control group who received standard cognitive training (n = 45) for 16 weeks. The Montreal Cognitive Assessment, Chinese Version of the Auditory Verbal Learning Test, Chinese Version of the Category Verbal Fluency Test, Digit Span Test, Trail Making Test, Chinese Version of Activities of Daily Living scale, and Memory Satisfaction Questionnaire were used to measure cognitive functioning and daily living abilities. Assessments were administered at baseline, postintervention, and 6 months follow-up. Results: At postintervention, patients receiving CrExp therapy scored significantly higher than patients receiving standard cognitive training, in general cognitive functioning, memory, executive function, functional status, and everyday living ability. The improvements in cognitive functioning were maintained at the 6 month follow-up. Conclusion: CrExp therapy has greater positive effects on cognitive functions and daily living ability than standard cognitive training. This unique therapy may serve as a cost-effective adjunct to standard interventions for older adults with mild cognitive impairment.