Adaptive digital tissue deconvolution.

MOTIVATION: The inference of cellular compositions from bulk and spatial transcriptomics data increasingly complements data analyses. Multiple computational approaches were suggested and recently, machine learning techniques were developed to systematically improve estimates. Such approaches allow to infer additional, less abundant cell types. However, they rely on training data which do not capture the full biological diversity encountered in transcriptomics analyses; data can contain cellular contributions not seen in the training data and as such, analyses can be biased or blurred. Thus, computational approaches have to deal with unknown, hidden contributions. Moreover, most methods are based on cellular archetypes which serve as a reference; e.g. a generic T-cell profile is used to infer the proportion of T-cells. It is well known that cells adapt their molecular phenotype to the environment and that pre-specified cell archetypes can distort the inference of cellular compositions. RESULTS: We propose Adaptive Digital Tissue Deconvolution (ADTD) to estimate cellular proportions of pre-selected cell types together with possibly unknown and hidden background contributions. Moreover, ADTD adapts prototypic reference profiles to the molecular environment of the cells, which further resolves cell-type specific gene regulation from bulk transcriptomics data. We verify this in simulation studies and demonstrate that ADTD improves existing approaches in estimating cellular compositions. In an application to bulk transcriptomics data from breast cancer patients, we demonstrate that ADTD provides insights into cell-type specific molecular differences between breast cancer subtypes. AVAILABILITY AND IMPLEMENTATION: A python implementation of ADTD and a tutorial are available at Gitlab and zenodo (doi:10.5281/zenodo.7548362).

CT and MRI Findings of Invasive Mucormycosis in the Setting of COVID-19: Experience From a Single Center in India.

An increasing incidence of rhinoorbitocerebral mucormycosis (ROCM) among patients with COVID-19 has recently been reported in India. We report the imaging findings for 25 patients with COVID-19 and invasive ROCM at a single hospital in India. Findings included sinus wall erosions (n = 20), air within bony sinus structures (n = 11), and focal mucosal nonenhancement (n = 8). Orbital, vascular, and intracranial complications were also observed. Radiologists should recognize the increasing incidence of ROCM among patients with COVID-19 to facilitate early diagnosis.

Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia: a retrospective cohort study with follow-up from Mumbai, India.

BACKGROUND: Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm. METHOD: This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26. RESULTS: Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427-0.903, P 0.013) and higher oxygen saturation. CONCLUSION: Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted.

Role of bronchoscopy and imaging in long-standing foreign body bronchus presenting as recurrent or non-resolving lower respiratory tract infection.

INTRODUCTION: A long-standing retained foreign body in the bronchus is unusual. In majority of cases, an adequate history is not obtained, the clinical picture is usually clouded by superadded pathological changes. CASE SERIES: We report three cases of long-standing foreign body in the airway who presented with recurrent lower respiratory tract infection. Examination of respiratory system revealed no significant abnormality. Chest radiograph was normal. CT scan of the chest was useful to indicate endobronchial opacity in the airway suggestive of a foreign body. The patients underwent rigid bronchoscopy under general anesthesia for successful removal of the foreign body. CONCLUSION: So the patients with non-resolving or recurrent lower respiratory symptoms in spite of medical treatment and without any obstructive findings must undergo diagnostic bronchoscopy evaluation and imaging.

Capsular Warning Syndrome - A Case Series and Discussion on Management Dilemmas.

BACKGROUND: The term 'Capsular warning syndrome (CWS)' refers to recurrent, stereotypical transient ischemic attacks, either motor, sensory or both, without cortical symptoms or signs. Of these patients, 42-71% go on to develop infarcts. There are no defined treatment guidelines for this lesser known entity. METHODS: We studied 9 patients who presented over last 2 years to our hospital with recurrent and stereotypical transient ischemic attacks suggestive of capsular warning syndrome. Their clinical characteristics, neuroimaging findings, relevant etiological investigations, management and outcomes were studied. RESULTS: Seven out of 9 patients were under 40 years of age. The commonest presentation in our series was a pure motor syndrome. The duration of neurologic deficits ranged from 5 minutes to 20 minutes with complete recovery in between episodes. Three patients had concordant abnormalities on CT brain angiography. Five out of 9 patients received IV thrombolysis with t-PA. One patient worsened neurologically post thrombolysis, whilst the others improved clinically. DISCUSSION: Despite multiple hypotheses, the pathogenesis and management of CWS has not been established clearly. Due to fluctuating neurological symptoms with complete recovery in between the episodes, there is a dilemma concerning treatment of such patients with intravenous thrombolysis. However, intravenous thrombolysis appears to be safe in CWS as in acute ischemic stroke, followed by treatment with antiplatelet agents.

COVID-19 Associated Stroke-A Single Centre Experience.

BACKGROUND AND PURPOSE: Various neurological complications have been reported in association with COVID-19. We report our experience of COVID-19 with stroke at a single center over a period of eight months spanning 1 March to 31 October 2020. METHODS: We recruited all patients admitted to Internal Medicine with an acute stroke, who also tested positive for COVID-19 on RTPCR. We included all stroke cases in our analysis for prediction of in-hospital mortality, and separately analyzed arterial infarcts for vascular territory of ischemic strokes. RESULTS: There were 62 stroke cases among 3923 COVID-19 admissions (incidence 1.6%). Data was available for 58 patients {mean age 52.6 years; age range 17-91; F/M=20/38; 24% (14/58) aged ≤40; 51% (30/58) hypertensive; 36% (21/58) diabetic; 41% (24/58) with O2 saturation <95% at admission; 32/58 (55.17 %) in-hospital mortality}. Among 58 strokes, there were 44 arterial infarcts, seven bleeds, three arterial infarcts with associated cerebral venous sinus thrombosis, two combined infarct and bleed, and two of indeterminate type. Among the total 49 infarcts, Carotid territory was the commonest affected (36/49; 73.5%), followed by vertebrobasilar (7/49; 14.3%) and both (6/49; 12.2%). Concordant arterial block was seen in 61% (19 of 31 infarcts with angiography done). 'Early stroke' (within 48 hours of respiratory symptoms) was seen in 82.7% (48/58) patients. Patients with poor saturation at admission were older (58 vs 49 years) and had more comorbidities and higher mortality (79% vs 38%). Mortality was similar in young strokes and older patients, although the latter required more intense respiratory support. Logistic regression analysis showed that low Glasgow coma score (GCS) and requirement for increasing intensity of respiratory support predicted in-hospital mortality. CONCLUSIONS: We had a 1.6% incidence of COVID-19 related stroke of which the majority were carotid territory infarcts. In-hospital mortality was 55.17%, predicted by low GCS at admission.

LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein.

The cytokine leukaemia inhibitory factor (LIF) promotes self-renewal of mouse embryonic stem cells (ESCs) through activation of the transcription factor Stat3. However, the contribution of other ancillary pathways stimulated by LIF in ESCs, such as the MAPK and PI3K pathways, is less well understood. We show here that naive-type mouse ESCs express high levels of a novel effector of the MAPK and PI3K pathways. This effector is an isoform of the Gab1 (Grb2-associated binder protein 1) adaptor protein that lacks the N-terminal pleckstrin homology (PH) membrane-binding domain. Although not essential for rapid unrestricted growth of ESCs under optimal conditions, the novel Gab1 variant (Gab1ß) is required for LIF-mediated cell survival under conditions of limited nutrient availability. This enhanced survival is absolutely dependent upon a latent palmitoylation site that targets Gab1ß directly to ESC membranes. These results show that constitutive association of Gab1 with membranes through a novel mechanism promotes LIF-dependent survival of murine ESCs in nutrient-poor conditions.

Role of MRI in Evaluation of Spectrum of Liver Lesions in Cirrhotic Patients.

MRI provides better intrinsic soft-tissue contrast with more enhanced depiction of even subtly different tissue properties making lesion evaluation easy. Faster sequences which capture arterial sequences better, lack of ionizing radiation and simultaneous evaluation of background liver parenchyma and the liver lesions are additional advantages of using MRI as the imaging technique of choice. Comprehensive liver imaging using MRI now includes T1, T2-weighted imaging and in- and opposed-phase, in addition to dynamic post-contrast imaging with proper breath holding techniques. Wider variety of liver specific contrast agents is available for use in MR imaging with the gadolinium based agents being considered the most useful and practical, particularly for lesion characterization. AIMS AND OBJECTIVES: To evaluate MRI spectrum of liver lesions in cirrhotic patients, Role of MRI in focal liver lesion evaluation and to differentiate benign versus malignant lesions. MATERIALS AND METHODS: A prospective study of OPD or IPD patients who underwent imaging tests like Ultrasonography, or CT scan for suspected chronic liver disease was done. A total 35 patients were investigated (June 2014 - November 2016) with MRI abdomen done with the patient in supine position on a Philips Achieva 3.0T MRI scanner. Standard MRI abdomen protocol, including T2W TSE in axial and coronal plane, T2W fat suppressed (SPAIR) images in axial and coronal plane, T1W TFE, in- and out-of-phase imaging and Diffusion-weighted imaging (DWI) in axial plane along with pre-contrast baseline fat-suppressed T1W imaging in at least one plane was acquired. Breath-holding was required in few sequences. 0.1 mmol/kg Gadolinium based contrast (Gadobenate) was injected at the rate of 2.5 ml/sec followed by saline flush and dynamic contrast enhanced MRI (DCE-MRI) with post-contrast fat-suppressed T1W imaging was acquired. RESULTS AND CONCLUSIONS: In cirrhosis, there is development of nodules which are initially only microscopically detectable. With progression of cirrhosis, there is development of radiologically detectable regenerative nodules, dysplastic nodules and hepatocellular carcinoma. Amongst these regenerative nodules are completely benign lesions whereas dysplastic nodules, though benign, are considered premalignant; and hepatocellular carcinoma is a malignant condition. Differentiation of benign versus malignant lesions is possible on the basis of enhancement pattern in dynamic contrast enhanced MRI. The signal characteristics of focal lesions and other findings like portal vein thrombosis are helpful, give additional clue to the diagnosis and also helpful in assigning LIRADS grade to a lesion. Also, MRI characterization after gadolinium based contrast injection was found to be similar to the previous imaging based on non-gadolinium contrast agents.

Dermatomyositis during COVID-19 Pandemic (A Case Series): Is there a Cause Effect Relationship?

Viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes, systemic lupus erythematosus (SLE), rheumatoid arthritis and multiple sclerosis. Viral infections have also been considered as a possible trigger for autoimmune disorders like myositis through myositis specific antibodies. Dermatomyositis is an acquired inflammatory myopathy which is relatively rare with incidence of 9.3 per 1 million persons. Usually we come across 1-2 patients of dermatomyositis per year, amongst 800-1000 new patients in our tertiary care rheumatology services. A surge in the incidence was noted this year during the months of April-August of 2020, the period coinciding with the occurrence of corona virus (COVID-19) pandemic in the city of Mumbai, the total number of cases encountered being five in a span of six months. The following case series includes five such cases with review of available literature on virus-triggered autoimmunity with special reference to SARS-CoV-2 and the challenges of immunosuppression during this pandemic.

An Unusual Case of a Displaced Hemodialysis Catheter Guidewire Spontaneously Coming Out of Skull.

Hemodialysis catheter insertion is a common practice for the patients with renal failure. There are several complications associated with hemodialysis catheter insertion such as infection, catheter thrombosis, malposition, or vein stenosis; however, loss of guidewire during catheter insertion with its migration is a rare complication. We report the case of a 75-year-old male with forgotten displaced guidewire which came out spontaneously from the skull in the occipital region, three years after the hemodialysis. To the best of our knowledge, this is the only case that has been reported in literature till date. We also discuss the possible causes of a retained guidewire and measure to prevent it. How to cite this article: Muthe M, Joshi A, Firke V. An Unusual Case of a Displaced Hemodialysis Catheter Guidewire Spontaneously Coming Out of Skull. Indian J Crit Care Med 2020;24(6):480-482.

Aftermath of pulmonary tuberculosis: computed tomography assessment.

PURPOSE: Pulmonary tuberculosis (PTB) has clinically significant sequelae, even after recommended treatment completion. It is important to recognise these sequelae for accurate assessment of severity and treatment planning, if indicated. MATERIAL AND METHODS: We retrospectively analysed contrast-enhanced computed tomography (CT) scans of chest of 100 patients with previous history of treated pulmonary tuberculosis, excluding those with active pulmonary disease. CT findings were analysed based on parenchymal, airway, pleural, mediastinal, and vascular sequelae of PTB. RESULTS: Parenchymal sequelae included fibrosis with architectural distortion and volume loss (90%), cavities (21%) (with aspergillomas noted in 19% of these cases), and tuberculomas (54%). Airway involvement was noted as bronchiectasis (77%) and bronchial stenosis (4%) but none with broncholithiasis. Mediastinal sequelae included lymph node calcification (74%), fibrosing mediastinitis (1%), and pericardial tuberculosis (2%). Pleural sequelae included pleural thickening (22%), with 40.9% of these patients showing calcifications, and one patient with chronic chylous pleural effusion. Vascular sequelae included Rasmussen aneurysms (4%), enlarged bronchial arteries (3%), and systemic bronchial collaterals in 1% of our patients. CONCLUSIONS: PTB has multiple appalling sequelae, which require due attention and appropriate treatment in symptomatic cases. Radiological evaluation forms an integral part in patient assessment and decision making.

Role of 3T MRI in Evaluation of Bone Marrow Changes in Spine in Various Diseases.

ABSTRACT: Multiplanar MR imaging provides excellent spatial and contrast resolution necessary to differentiate the signal intensities of fatty (yellow) marrow elements from hematopoietic (red) marrow elements and hence it is useful for evaluation of various pathologies of bone marrow. Utilization of typical imaging features on conventional MR imaging techniques and other newer imaging techniques, such as diffusion-weighted imaging (DWI) and in- and out-of-phase MRI, for better characterisation of bone marrow pathologies has been highlighted. AIMS AND OBJECTIVES: To determine the prevalence of various bone marrow pathologies in spine. To study the MRI signal changes of bone marrow in various lesions such as anaemia, leukaemia, lymphomas and various bone marrow disorders. MATERIALS AND METHODS: A total of 100 patients who were investigated between November 2012 and October 2014 were included. MRI spine studies were done on a 3.0 Tesla Philips Achieva Medical Systems. OBSERVATIONS AND RESULTS: In our study, out of 100 cases studied for various spinal pathologies, 48 patients were male and 52 were female indicating almost equal male to female distribution. Maximum cases were degenerative with most common site of involvement being lumbar followed by cervical region. There were only 3 cases of depletion disorder and no case with deposition disorder. The mean age group was 45.37 years, with the range being 9 years to 72 years. Maximum patients (n = 67) were found in the age group of 41-60. CONCLUSION: Various bone marrow disorders were classified and evaluated separately. A systematic approach to its evaluation by categorization is essential with prudent use of both conventional and problem-solving techniques, such as CSI and DWI, for accurate diagnosis and appropriate patient management. Conventional radiology depicts changes of an altered bony matrix while MRI displays changes at a cellular level and is well suited for imaging the bone marrow. MRI serves as a screening method in bone marrow disorders and the diagnosis is established in context with the clinical findings or by biopsy.

The Effect of Hypertension and Diabetes Mellitus on White Matter Changes in MRI Brain: A Comparative Study between Patients with Alzheimer's Disease and an Age-matched Control Group.

BACKGROUND: White matter hyperintensities (WMH) on MRI brain in the periventricular and deep white matter regions are commonly seen in older persons with normal cognition and in patients with AD. AIMS: To compare presence and severity of WMHs in patients with AD with that in a cognitively normal control group, and to evaluate effect of presence of Hypertension and Diabetes on WMHs in both groups. MATERIAL AND METHODS: Thirty four patients with AD were serially recruited from Neurology and Psychiatry OPDs. An age and gender matched cohort of 24 persons with MMSE over 27/30 from the community acted as controls. Vascular risk factors, MMSE and MRI brain were assessed in all. Fezeka's and Pasquier grading of WMH and atrophy were done. Periventricular WMHs (PVWMH) and Deep WMH (DWMH) were assessed separately. RESULTS AND CONCLUSIONS: Overall, Periventricular WMHs of grade 2 and over were seen in 19/34 patients, and in 7/24 controls (P value 0.044). Significantly higher grades of PVWMHs were seen in hypertensives as compared to nonhypertensives in the case group, and in women compared to men. In the control group, hypertension had no effect on severity of PVWMHs. Among both Diabetics and non-diabetics, no difference in PVWMHs was found between the case and control groups. DWMHs were, conversely, seen only in the control group. Overall, over a quarter of cognitively normal older persons had WM hyperintensities of grade 2 and over on MRI brain; 55% of AD patients had PVWMH of Gd 2 or over, and no DWMHs.

Insights into mammalian transcription control by systematic analysis of ChIP sequencing data.

BACKGROUND: Transcription regulation is a major controller of gene expression dynamics during development and disease, where transcription factors (TFs) modulate expression of genes through direct or indirect DNA interaction. ChIP sequencing has become the most widely used technique to get a genome wide view of TF occupancy in a cell type of interest, mainly due to established standard protocols and a rapid decrease in the cost of sequencing. The number of available ChIP sequencing data sets in public domain is therefore ever increasing, including data generated by individual labs together with consortia such as the ENCODE project. RESULTS: A total of 1735 ChIP-sequencing datasets in mouse and human cell types and tissues were used to perform bioinformatic analyses to unravel diverse features of transcription control. 1- We used the Heat*seq webtool to investigate global relations across the ChIP-seq samples. 2- We demonstrated that factors have a specific genomic location preferences that are, for most factors, conserved across species. 3- Promoter proximal binding of factors was more conserved across cell types while the distal binding sites are more cell type specific. 4- We identified combinations of factors preferentially acting together in a cellular context. 5- Finally, by integrating the data with disease-associated gene loci from GWAS studies, we highlight the value of this data to associate novel regulators to disease. CONCLUSION: In summary, we demonstrate how ChIP sequencing data integration and analysis is powerful to get new insights into mammalian transcription control and demonstrate the utility of various bioinformatic tools to generate novel testable hypothesis using this public resource.

Dynamics of promoter bivalency and RNAP II pausing in mouse stem and differentiated cells.

BACKGROUND: Mammalian embryonic stem cells display a unique epigenetic and transcriptional state to facilitate pluripotency by maintaining lineage-specification genes in a poised state. Two epigenetic and transcription processes involved in maintaining poised state are bivalent chromatin, characterized by the simultaneous presence of activating and repressive histone methylation marks, and RNA polymerase II (RNAPII) promoter proximal pausing. However, the dynamics of histone modifications and RNAPII at promoters in diverse cellular contexts remains underexplored. RESULTS: We collected genome wide data for bivalent chromatin marks H3K4me3 and H3K27me3, and RNAPII (8WG16) occupancy together with expression profiling in eight different cell types, including ESCs, in mouse. The epigenetic and transcription profiles at promoters grouped in over thirty clusters with distinct functional identities and transcription control. CONCLUSION: The clustering analysis identified distinct bivalent clusters where genes in one cluster retained bivalency across cell types while in the other were mostly cell type specific, but neither showed a high RNAPII pausing. We noted that RNAPII pausing is more associated with active genes than bivalent genes in a cell type, and was globally reduced in differentiated cell types compared to multipotent.

Causal Transcription Regulatory Network Inference Using Enhancer Activity as a Causal Anchor.

Transcription control plays a crucial role in establishing a unique gene expression signature for each of the hundreds of mammalian cell types. Though gene expression data have been widely used to infer cellular regulatory networks, existing methods mainly infer correlations rather than causality. We developed statistical models and likelihood-ratio tests to infer causal gene regulatory networks using enhancer RNA (eRNA) expression information as a causal anchor and applied the framework to eRNA and transcript expression data from the FANTOM Consortium. Predicted causal targets of transcription factors (TFs) in mouse embryonic stem cells, macrophages and erythroblastic leukaemia overlapped significantly with experimentally-validated targets from ChIP-seq and perturbation data. We further improved the model by taking into account that some TFs might act in a quantitative, dosage-dependent manner, whereas others might act predominantly in a binary on/off fashion. We predicted TF targets from concerted variation of eRNA and TF and target promoter expression levels within a single cell type, as well as across multiple cell types. Importantly, TFs with high-confidence predictions were largely different between these two analyses, demonstrating that variability within a cell type is highly relevant for target prediction of cell type-specific factors. Finally, we generated a compendium of high-confidence TF targets across diverse human cell and tissue types.

Meta-analysis reveals conserved cell cycle transcriptional network across multiple human cell types.

BACKGROUND: Cell division is central to the physiology and pathology of all eukaryotic organisms. The molecular machinery underpinning the cell cycle has been studied extensively in a number of species and core aspects of it have been found to be highly conserved. Similarly, the transcriptional changes associated with this pathway have been studied in different organisms and different cell types. In each case hundreds of genes have been reported to be regulated, however there seems to be little consensus in the genes identified across different studies. In a recent comparison of transcriptomic studies of the cell cycle in different human cell types, only 96 cell cycle genes were reported to be the same across all studies examined. RESULTS: Here we perform a systematic re-examination of published human cell cycle expression data by using a network-based approach to identify groups of genes with a similar expression profile and therefore function. Two clusters in particular, containing 298 transcripts, showed patterns of expression consistent with cell cycle occurrence across the four human cell types assessed. CONCLUSIONS: Our analysis shows that there is a far greater conservation of cell cycle-associated gene expression across human cell types than reported previously, which can be separated into two distinct transcriptional networks associated with the G1/S-S and G2-M phases of the cell cycle. This work also highlights the benefits of performing a re-analysis on combined datasets.

Heat*seq: an interactive web tool for high-throughput sequencing experiment comparison with public data.

Better protocols and decreasing costs have made high-throughput sequencing experiments now accessible even to small experimental laboratories. However, comparing one or few experiments generated by an individual lab to the vast amount of relevant data freely available in the public domain might be limited due to lack of bioinformatics expertise. Though several tools, including genome browsers, allow such comparison at a single gene level, they do not provide a genome-wide view. We developed Heat*seq, a web-tool that allows genome scale comparison of high throughput experiments chromatin immuno-precipitation followed by sequencing, RNA-sequencing and Cap Analysis of Gene Expression) provided by a user, to the data in the public domain. Heat*seq currently contains over 12 000 experiments across diverse tissues and cell types in human, mouse and drosophila. Heat*seq displays interactive correlation heatmaps, with an ability to dynamically subset datasets to contextualize user experiments. High quality figures and tables are produced and can be downloaded in multiple formats. AVAILABILITY AND IMPLEMENTATION: Web application: http://www.heatstarseq.roslin.ed.ac.uk/ Source code: https://github.com/gdevailly CONTACT: Guillaume.Devailly@roslin.ed.ac.uk or Anagha.Joshi@roslin.ed.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.

Life-threatening Medical Complications Due to Ovarian Hyperstimulation Syndrome: A Hidden Etiology.

Ovarian hyperstimulation syndrome is usually an iatrogenic complication in women taking ovulation induction medications during assisted reproduction. We hereby report the case of a 25 years old female who presented with hypertension, polyserositis with tense ascites and large cystic ovaries. She developed sigmoid and transverse sinus thrombosis. She had undergone a clandestine ovulation induction therapy as a commercial ovum donor. She fitted in severe category of ovarian hyperstimulation syndrome.

TRES predicts transcription control in embryonic stem cells.

SUMMARY: Unraveling transcriptional circuits controlling embryonic stem cell maintenance and fate has great potential for improving our understanding of normal development as well as disease. To facilitate this, we have developed a novel web tool called 'TRES' that predicts the likely upstream regulators for a given gene list. This is achieved by integrating transcription factor (TF) binding events from 187 ChIP-sequencing and ChIP-on-chip datasets in murine and human embryonic stem (ES) cells with over 1000 mammalian TF sequence motifs. Using 114 TF perturbation gene sets, as well as 115 co-expression clusters in ES cells, we validate the utility of this approach. AVAILABILITY AND IMPLEMENTATION: TRES is freely available at http://www.tres.roslin.ed.ac.uk. CONTACT: Anagha.Joshi@roslin.ed.ac.uk or bg200@cam.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.