The genomic and evolutionary landscapes of anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

Factors Associated with Inhaled Bronchodilator and Oral Corticosteroid Use in Young Children with First Lower Respiratory Tract Infection.

OBJECTIVES: To examine factors associated with claims for and potential overuse of inhaled bronchodilators (IBs) and oral corticosteroids (OCSs) for children <2 years old at first lower respiratory tract infections (LRTIs). STUDY DESIGN: Retrospective cohort study using Colorado All Payer Claims data from 2009 through 2019. Children with asthma were excluded. Primary outcomes were 1) IB and 2) OCS claims within 7 days of index LRTI. Primary predictors were previous IB or OCS claims for each outcome respectively. Covariates included demographics, atopy, family history of asthma, complex chronic conditions, prior inhaled corticosteroid claim, and location of index LRTI. Separate multivariable logistic regression models were used for each outcome. RESULTS: Of 10 194 eligible children, 1468 (14.4%) had an IB and 741 (7.3%) an OCS claim at or within 7 days of index LRTI. Index LRTIs were most often at outpatient visits (64%). Adjusting for covariates, prior IB prescription was associated with the IB outcome (aOR 1.9; 95% CI 1.3, 2.8), and prior OCS prescription was associated with the OCS outcome (AOR 2.2; 95% CI 1.7, 2.9). Other variables associated with either outcome included age, sex, insurance, location, and atopy. Prior inhaled corticosteroid claim, asthma family history, and complex chronic conditions were not associated with either outcome. CONCLUSIONS: This study identifies factors that might serve as opportunities for de-implementation strategies for IB and OCS overuse in young children with LRTI.

Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects.

PURPOSE: Superficial siderosis, a progressive, debilitating, neurological disease, often presents with bilateral impairment of auditory and vestibular function. We highlight that superficial siderosis is often due to a repairable spinal dural defect of the type that can also cause spontaneous intracranial hypotension. METHODS: Retrospective chart review of five patients presenting with moderate to severe, progressive bilateral sensorineural hearing loss as well as vestibular loss. All patients had developed superficial siderosis from spinal dural defects: three after trauma, one after spinal surgery and one from a thoracic discogenic microspur. RESULTS: The diagnosis was made late in all five patients; despite surgical repair in four, hearing and vestibular loss failed to improve. CONCLUSIONS: In patients presenting with progressive bilateral sensorineural hearing loss, superficial siderosis should be considered as a possible cause. If these patients also have bilateral vestibular loss, cerebellar impairment and anosmia, then the diagnosis is likely and the inevitable disease progress might be halted by finding and repairing the spinal dural defect.

Association between early childhood lower respiratory tract infections and subsequent asthma.

OBJECTIVE: We examined the relationship between recurrent lower respiratory tract infections (LRTI) in young children and subsequent childhood asthma outcomes. METHODS: Retrospective cohort study using 2009-2017 Colorado All Payer Claims Database to assess 0- to 2-year-old children with visits due to LRTI and acute gastroenteritis (AGE). The primary exposure was number of LRTI visits prior to 2 years of age. Children with AGE served as the no LRTI comparator group. The primary outcome was incident asthma, defined by ICD-9 (490.XX) or ICD-10 (J45.9XX) codes, in the same children between 3 and 9 years of age. Multivariable accelerated failure time (AFT) models were used to estimate the effect of LRTI visits on median time to asthma diagnosis. Sensitivity analyses were performed using more conservative asthma diagnostic criteria and with hospitalized children only. RESULTS: Of 38,441 eligible subjects, 32,729 had ≥1 LRTI and 5,712 had AGE (no LRTI) between 0 and 2 years of age. Children with ≥3 LRTI visits had an 80% decrease in median time to asthma diagnosis relative to those with AGE visits only (time ratio [TR] 0.2; 95% CI 0.16, 0.24). Children with ≥3 LRTI hospitalizations had a 98% reduction in median time to asthma diagnosis relative to those with AGE hospitalizations only (TR 0.02; 95% CI 0.01, 0.07). History of atopy, wheezing, and family history of asthma documented prior to 2 years of age were also associated with earlier asthma diagnosis. CONCLUSIONS: Recurrent LRTIs, especially LRTI hospitalizations, before 2 years of age are associated with earlier diagnosis of pediatric asthma.

Sharing the load: How a personally coloured calculator for grapheme-colour synaesthetes can reduce processing costs.

Synaesthesia refers to a diverse group of perceptions. These unusual perceptions are defined by the experience of concurrents; these are conscious experiences that are catalysed by attention to some normally unrelated stimulus, the inducer. In grapheme-colour synaesthesia numbers, letters, and words can all cause colour concurrents, and these are independent of the actual colour with which the graphemes are displayed. For example, when seeing the numeral '3' a person with synaesthesia might experience green as the concurrent irrespective of whether the numeral is printed in blue, black, or red. As a trait, synaesthesia has the potential to cause both positive and negative effects. However, regardless of the end effect, synaesthesia incurs an initial cost when compared with its equivalent example from normal perception; this is the additional processing cost needed to generate the information on the concurrent. We contend that this cost can be reduced by mirroring the concurrent in the environment. We designed the Digital-Colour Calculator (DCC) app, allowing each user to personalise and select the colours with which it displays its digits; it is the first reported example of a device/approach that leverages the concurrent. In this article we report on the reactions to the DCC for a sample of fifty-three synaesthetes and thirty-five non-synaesthetes. The synaesthetes showed a strong preference for the DCC over its normal counterpart. The non-synaesthetes showed no obvious preference. When using the DCC a subsample of the synaesthete group showed consistent improvement in task speed (around 8%) whereas no synaesthete showed a decrement in their speed.

A community challenge to evaluate RNA-seq, fusion detection, and isoform quantification methods for cancer discovery.

The accurate identification and quantitation of RNA isoforms present in the cancer transcriptome is key for analyses ranging from the inference of the impacts of somatic variants to pathway analysis to biomarker development and subtype discovery. The ICGC-TCGA DREAM Somatic Mutation Calling in RNA (SMC-RNA) challenge was a crowd-sourced effort to benchmark methods for RNA isoform quantification and fusion detection from bulk cancer RNA sequencing (RNA-seq) data. It concluded in 2018 with a comparison of 77 fusion detection entries and 65 isoform quantification entries on 51 synthetic tumors and 32 cell lines with spiked-in fusion constructs. We report the entries used to build this benchmark, the leaderboard results, and the experimental features associated with the accurate prediction of RNA species. This challenge required submissions to be in the form of containerized workflows, meaning each of the entries described is easily reusable through CWL and Docker containers at https://github.com/SMC-RNA-challenge. A record of this paper's transparent peer review process is included in the supplemental information.

Observation of Photoinduced Terahertz Gain in GaAs Quantum Wells: Evidence for Radiative Two-Exciton-to-Biexciton Scattering.

We have observed photoinduced negative optical conductivity, or gain, in the terahertz frequency range in a GaAs multiple-quantum-well structure in a strong perpendicular magnetic field at low temperatures. The gain is narrow band: it appears as a sharp peak (linewidth <0.45 meV) whose frequency shifts with applied magnetic field. The gain has a circular-polarization selection rule: a strong line is observed for hole-cyclotron-resonance-active polarization. Furthermore, the gain appears only when the exciton 1s state is populated, which rules out intraexcitonic transitions to be its origin. Based on these observations, we propose a possible process in which the stimulated emission of a terahertz photon occurs while two free excitons scatter into one biexciton in an energy and angular-momentum conserving manner.

The neuro-otology of Susac syndrome.

OBJECTIVE: We characterised the clinical and neuro-otological characteristics of patients with Susac syndrome. METHODS: The medical records of 30 patients with Susac syndrome were reviewed for details of their clinical presentation and course, neuro-otological symptoms, investigation results including audiology and vestibular function tests, treatment and outcomes. RESULTS: Our findings demonstrate that 29 of our 30 patients with Susac syndrome developed neuro-otological symptoms such as hearing loss, disequilibrium, tinnitus or vertigo during their disease course. Hearing loss was the most common neuro-otological symptom occurring in 93% of patients. A rising configuration of low-frequency greater than the high-frequency sensorineural hearing loss was the most characteristic finding on audiological testing (37% of reviewed audiograms). Disproportionately poor speech discrimination was identified in 20% of cases, and one case demonstrated a retrocochlear pattern on electrophysiological testing. Four patients required hearing aids and a further two patients required a cochlear implant due to severe hearing loss. Two out of two treated patients had improvements in hearing after the prompt administration of corticosteroids, indicating the potential for recoverable hearing loss if relapses are treated early. Effects on vestibular function were variable in ten patients who were tested, with most showing preservation of function despite significant hearing loss. CONCLUSIONS: Neuro-otological symptoms in Susac syndrome are almost universal. In the correct clinical context, a rising configuration of low to high-frequency sensorineural hearing loss should prompt consideration of Susac syndrome. Treatment of inner ear symptoms in Susac syndrome requires further research as early immunotherapy may be beneficial.

Immediate Post-operative Enterocyte Injury, as Determined by Increased Circulating Intestinal Fatty Acid Binding Protein, Is Associated With Subsequent Development of Necrotizing Enterocolitis After Infant Cardiothoracic Surgery.

Objectives: 1 Measure serial serum intestinal fatty acid binding protein levels in infants undergoing cardiac surgery with cardiopulmonary bypass to evaluate for evidence of early post-operative enterocyte injury. 2 Determine the association between immediate post-operative circulating intestinal fatty acid binding protein levels and subsequent development of necrotizing enterocolitis. Design: Observational cohort study. Intestinal fatty acid binding protein was measured pre-operatively, at rewarming, and at 6 and 24 h post-operatively. Percent of goal enteral kilocalories on post-operative day 5 and episodes of necrotizing enterocolitis were determined. Multivariable analysis assessed for factors independently associated with clinical feeding outcomes and suspected/definite necrotizing enterocolitis. Setting: Quaternary free-standing children's hospital pediatric cardiac intensive care unit. Patients: 103 infants <120 days of age undergoing cardiothoracic surgery with cardiopulmonary bypass. Interventions: None. Results: Median pre-operative intestinal fatty acid binding protein level was 3.93 ng/ml (range 0.24-51.32). Intestinal fatty acid binding protein levels rose significantly at rewarming (6.35 ng/ml; range 0.54-56.97; p = 0.008), continued to rise slightly by 6 h (6.57 ng/ml; range 0.75-112.04; p = 0.016), then decreased by 24 h (2.79 ng/ml; range 0.03-81.74; p < 0.0001). Sixteen subjects (15.7%) developed modified Bell criteria Stage 1 necrotizing enterocolitis and 9 subjects (8.8%) developed Stage 2 necrotizing enterocolitis. Infants who developed necrotizing enterocolitis demonstrated a significantly higher distribution of intestinal fatty acid binding protein levels at both 6 h (p = 0.005) and 24 h (p = 0.005) post-operatively. On multivariable analysis, intestinal fatty acid binding protein was not associated with percentage of goal enteral kilocalories delivered on post-operative day 5. Higher intestinal fatty acid binding protein was independently associated with subsequent development of suspected/definite necrotizing enterocolitis (4% increase in odds of developing necrotizing enterocolitis for each unit increase in intestinal fatty acid binding protein; p = 0.0015). Conclusions: Intestinal fatty acid binding protein levels rise following infant cardiopulmonary bypass, indicating early post-operative enterocyte injury. Intestinal fatty acid binding protein was not associated with percent of goal enteral nutrition achieved on post-operative day 5, likely due to protocolized feeding advancement based on clinically observable factors. Higher intestinal fatty acid binding protein at 6 h post-operatively was independently associated with subsequent development of necrotizing enterocolitis and may help identify patients at risk for this important complication.

Temporal Stability and Prognostic Biomarker Potential of the Prostate Cancer Urine miRNA Transcriptome.

BACKGROUND: The development of noninvasive tests for the early detection of aggressive prostate tumors is a major unmet clinical need. miRNAs are promising noninvasive biomarkers: they play essential roles in tumorigenesis, are stable under diverse analytical conditions, and can be detected in body fluids. METHODS: We measured the longitudinal stability of 673 miRNAs by collecting serial urine samples from 10 patients with localized prostate cancer. We then measured temporally stable miRNAs in an independent training cohort (n = 99) and created a biomarker predictive of Gleason grade using machine-learning techniques. Finally, we validated this biomarker in an independent validation cohort (n = 40). RESULTS: We found that each individual has a specific urine miRNA fingerprint. These fingerprints are temporally stable and associated with specific biological functions. We identified seven miRNAs that were stable over time within individual patients and integrated them with machine-learning techniques to create a novel biomarker for prostate cancer that overcomes interindividual variability. Our urine biomarker robustly identified high-risk patients and achieved similar accuracy as tissue-based prognostic markers (area under the receiver operating characteristic = 0.72, 95% confidence interval = 0.69 to 0.76 in the training cohort, and area under the receiver operating characteristic curve = 0.74, 95% confidence interval = 0.55 to 0.92 in the validation cohort). CONCLUSIONS: These data highlight the importance of quantifying intra- and intertumoral heterogeneity in biomarker development. This noninvasive biomarker may usefully supplement invasive or expensive radiologic- and tissue-based assays.

Substantiating synesthesia: a novel aid in a case of grapheme-colour synesthesia and concomitant dyscalculia.

Here we present the case of SP, a 21-year-old female with life-long dyscalculia. SP was subsequently diagnosed with grapheme-color synesthesia, a diagnosis that serendipitously catalyzed our development of a novel aid:The digit-color calculator (DCC). The DCC substantiates SP's color concurrents, dramatically ameliorating her difficulties with basic calculations. We envisage the DCC and its analogues may assist others in educational settings, particularly if they experience difficulties with the acquisition of literacy and numeracy. Further devices that leverage synesthesia may also have the potential to improve the quality of life for others with trait synesthesia regardless of concomitant disorder.

Ballistic InSb Nanowires and Networks via Metal-Sown Selective Area Growth.

Selective area growth is a promising technique to realize semiconductor-superconductor hybrid nanowire networks, potentially hosting topologically protected Majorana-based qubits. In some cases, however, such as the molecular beam epitaxy of InSb on InP or GaAs substrates, nucleation and selective growth conditions do not necessarily overlap. To overcome this challenge, we propose a metal-sown selective area growth (MS SAG) technique, which allows decoupling selective deposition and nucleation growth conditions by temporarily isolating these stages. It consists of three steps: (i) selective deposition of In droplets only inside the mask openings at relatively high temperatures favoring selectivity, (ii) nucleation of InSb under Sb flux from In droplets, which act as a reservoir of group III adatoms, done at relatively low temperatures, favoring nucleation of InSb, and (iii) homoepitaxy of InSb on top of the formed nucleation layer under a simultaneous supply of In and Sb fluxes at conditions favoring selectivity and high crystal quality. We demonstrate that complex InSb nanowire networks of high crystal and electrical quality can be achieved this way. We extract mobility values of 10 000-25 000 cm2 V-1 s-1 consistently from field-effect and Hall mobility measurements across single nanowire segments as well as wires with junctions. Moreover, we demonstrate ballistic transport in a 440 nm long channel in a single nanowire under a magnetic field below 1 T. We also extract a phase-coherent length of ∼8 µm at 50 mK in mesoscopic rings.

Comparative toxicoproteogenomics of mouse and rat liver identifies TCDD-resistance genes.

The aryl hydrocarbon receptor (AHR) mediates many toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, the AHR alone does not explain the widely different outcomes among organisms. To identify the other factors involved, we evaluated three transgenic mouse lines, each expressing a different rat AHR isoform (rWT, DEL, and INS) providing widely different resistance to TCDD toxicity, as well as C57BL/6 and DBA/2 mice which exhibit a ~ tenfold divergence in TCDD sensitivity (exposures of 5-1000 µg/kg TCDD). We supplement these with whole-genome sequencing, together with transcriptomic and proteomic analyses of the corresponding rat models, Long-Evans (L-E) and Han/Wistar (H/W) rats (having a ~ 1000-fold difference in their TCDD sensitivities; 100 µg/kg TCDD), to identify genes associated with TCDD-response phenotypes. Overall, we identified up to 50% of genes with altered mRNA abundance following TCDD exposure are associated with a single AHR isoform (33.8%, 11.7%, 5.2% and 0.3% of 3076 genes altered unique to rWT, DEL, C57BL/6 and INS respectively following 1000 µg/kg TCDD). Hepatic Pxdc1 was significantly repressed in all three TCDD-sensitive animal models (C57BL/6 and rWT mice, and L-E rat) after TCDD exposure. Three genes, including Cxxc5, Sugp1 and Hgfac, demonstrated different AHRE-1 (full) motif occurrences within their promoter regions between rat strains, as well as different patterns of mRNA abundance. Several hepatic proteins showed parallel up- or downward alterations with their RNAs, with three genes (SNRK, IGTP and IMPA2) showing consistent, strain-dependent changes. These data show the value of integrating genomic, transcriptomic and proteomic evidence across multi-species models in toxicologic studies.

2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver.

Alternative splicing is a co-transcriptional mechanism that generates protein diversity by including or excluding exons in different combinations, thereby expanding the diversity of protein isoforms of a single gene. Abnormalities in this process can result in deleterious effects to human health, and several xenobiotics are known to interfere with splicing regulation through multiple mechanisms. These changes could lead to human diseases such as cancer, neurological disorders, autoimmune diseases, and developmental disorders. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant generated as a byproduct of various industrial activities. Exposure to this dioxin has been linked to a wide range of pathologies through the alteration of multiple cellular processes. However, the effects of TCDD exposure on alternative splicing have not yet been studied. Here, we investigated whether a single po. dose of 5 µg/kg or 500 µg/kg TCDD influence hepatic alternative splicing in adult male C57BL/6Kou mouse. We identified several genes whose alternative splicing of precursor messenger RNAs was modified following TCDD exposure. In particular, we demonstrated that alternative splicing of Cyp1a1, Ahrr, and Actn1 was significantly altered after TCDD treatment. These findings show that the exposure to TCDD has an impact on alternative-splicing, and suggest a new avenue for understanding TCDD-mediated toxicity and pathogenesis.

A glycopolymer improves vascoelasticity and mucociliary transport of abnormal cystic fibrosis mucus.

Cystic fibrosis (CF) is characterized by increased mucus viscosity and delayed mucociliary clearance that contributes to progressive decline of lung function. Mucus in the respiratory and GI tract is excessively adhesive in the presence of airway dehydration and excess extracellular Ca2+ upon mucin release, promoting hyperviscous, densely packed mucins characteristic of CF. Therapies that target mucins directly through ionic interactions remain unexploited. Here we show that poly (acetyl, arginyl) glucosamine (PAAG), a polycationic biopolymer suitable for human use, interacts directly with mucins in a Ca2+-sensitive manner to reduce CF mucus viscoelasticity and improve its transport. Notably, PAAG induced a linear structure of purified MUC5B and altered its sedimentation profile and viscosity, indicative of proper mucin expansion. In vivo, PAAG nebulization improved mucociliary transport in CF rats with delayed mucus clearance, and cleared mucus plugging in CF ferrets. This study demonstrates the potential use of a synthetic glycopolymer PAAG as a molecular agent that could benefit patients with a broad array of mucus diseases.

Alkaline Phosphatase Activity and Endotoxemia After Infant Cardiothoracic Surgery.

OBJECTIVE: Infant cardiopulmonary bypass (CPB) increases intestinal permeability leading to endotoxemia. Alkaline phosphatase (AP) reduces endotoxin toxicity in vitro but its effects on endotoxemia in human disease are poorly understood. We assessed the association between serum AP activity and endotoxemia in infants undergoing CPB and determined the effect of ex vivo addition of AP on endotoxemia. METHODS: Prospective cohort study of 62 infants ≤120 days of age undergoing CPB. AP activity and Endotoxin Activity Assay (EAA) were measured pre-operatively, during rewarming, and 24 h after cardiac intensive care unit admission. In 22 subjects, EAA was measured in pre-operative and rewarming whole blood samples with/without addition of 1,600 U/L of human liver AP. RESULTS: AP activity decreased during CPB (mean decrease 94.8U/L; P < 0.0001). Median EAA was 0.41 pre-operation, rose to 0.52 (P < 0.05) during rewarming, and remained stably elevated at 24 h. Subjects with low pre-operative AP activity had significantly higher pre-operative (0.47 vs. 0.36; P < 0.05) and rewarming (0.59 vs. 0.43; P < 0.01) EAA with a trend toward higher EAA at 24 h (0.52 vs. 0.45; P = 0.12). Subjects with low rewarming AP activity showed similar differences that did not reach statistical significance. Ex vivo addition of human liver AP decreased pre-operative EAA by 29% (P < 0.001) and rewarming EAA by 51% (P < 0.0001). CONCLUSION: Endotoxemia is common in infants undergoing CPB. Native AP activity and endotoxemia are inversely related and ex vivo addition of exogenous AP reduces whole blood EAA. Future research should evaluate AP as a therapy to reduce the harmful effects of endotoxemia following infant CPB.

If Time Is Brain Where Is the Improvement in Prehospital Time after Stroke?

Despite the availability of thrombolytic and endovascular therapy for acute ischemic stroke, many patients are ineligible due to delayed hospital arrival. The identification of factors related to either early or delayed hospital arrival may reveal potential targets of intervention to reduce prehospital delay and improve access to time-critical thrombolysis and clot retrieval therapy. Here, we have reviewed studies reporting on factors associated with either early or delayed hospital arrival after stroke, together with an analysis of stroke onset to hospital arrival times. Much effort in the stroke treatment community has been devoted to reducing door-to-needle times with encouraging improvements. However, this review has revealed that the median onset-to-door times and the percentage of stroke patients arriving before the logistically critical 3 h have shown little improvement in the past two decades. Major factors affecting prehospital time were related to emergency medical pathways, stroke symptomatology, patient and bystander behavior, patient health characteristics, and stroke treatment awareness. Interventions addressing these factors may prove effective in reducing prehospital delay, allowing prompt diagnosis, which in turn may increase the rates and/or efficacy of acute treatments such as thrombolysis and clot retrieval therapy and thereby improve stroke outcomes.

Mitochondrial mutations drive prostate cancer aggression.

Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer patients, and identify a median of one mitochondrial single-nucleotide variant (mtSNV) per patient. Some of these mtSNVs occur in recurrent mutational hotspots and associate with aggressive disease. Younger patients have fewer mtSNVs than those who diagnosed at an older age. We demonstrate strong links between mitochondrial and nuclear mutational profiles, with co-occurrence between specific mutations. For example, certain control region mtSNVs co-occur with gain of the MYC oncogene, and these mutations are jointly associated with patient survival. These data demonstrate frequent mitochondrial mutation in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer.In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity.

Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems.

BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease. We therefore compiled a collection of transcriptomic datasets that can be used to aid the scientific community in better understanding the transcriptional effects of ligand-activated AHR. RESULTS: Specifically, we have created a datasets package - TCDD.Transcriptomics - for the R statistical environment, consisting of 63 unique experiments comprising 377 samples, including various combinations of 3 species (human derived cell lines, mouse and rat), 4 tissue types (liver, kidney, white adipose tissue and hypothalamus) and a wide range of TCDD exposure times and doses. These datasets have been fully standardized using consistent preprocessing and annotation packages (available as of September 14, 2015). To demonstrate the utility of this R package, a subset of "AHR-core" genes were evaluated across the included datasets. Ahrr, Nqo1 and members of the Cyp family were significantly induced following exposure to TCDD across the studies as expected while Aldh3a1 was induced specifically in rat liver. Inmt was altered only in liver tissue and primarily by rat-AHR. CONCLUSIONS: Analysis of the "AHR-core" genes demonstrates a continued need for studies surrounding the impact of AHR-activity on the transcriptome; genes believed to be consistently regulated by ligand-activated AHR show surprisingly little overlap across species and tissues. Until now, a comprehensive assessment of the transcriptome across these studies was challenging due to differences in array platforms, processing methods and annotation versions. We believe that this package, which is freely available for download ( http://labs.oicr.on.ca/boutros-lab/tcdd-transcriptomics ) will prove to be a highly beneficial resource to the scientific community evaluating the effects of TCDD exposure as well as the variety of functions of the AHR.