Anaplastic Thyroid Carcinoma Histologically Mimicking a Plasmacytoma.

Anaplastic (undifferentiated) thyroid carcinoma (ATC) is a rare malignancy which may arise from transformation of a pre-existing differentiated carcinoma. We report the unique case where a lesion of thyroid origin presented with the histological features of mature plasma cells. Immunohistochemistry confirmed the lesion to be an anaplastic thyroid carcinoma arising from papillary thyroid carcinoma. A tumor mimicking a malignancy of a different cellular origin can lead clinicians to incorrect treatment approaches. Careful correlation with clinical details and knowledge of these unique presentations is important for reaching the correct diagnosis

Encapsulation kinetics and dynamics of carbon monoxide in clathrate hydrate.

Carbon monoxide clathrate hydrate is a potentially important constituent in the solar system. In contrast to the well-established relation between the size of gaseous molecule and hydrate structure, previous work showed that carbon monoxide molecules preferentially form structure-I rather than structure-II gas hydrate. Resolving this discrepancy is fundamentally important to understanding clathrate formation, structure stabilization and the role the dipole moment/molecular polarizability plays in these processes. Here we report the synthesis of structure-II carbon monoxide hydrate under moderate high-pressure/low-temperature conditions. We demonstrate that the relative stability between structure-I and structure-II hydrates is primarily determined by kinetically controlled cage filling and associated binding energies. Within hexakaidecahedral cage, molecular dynamic simulations of density distributions reveal eight low-energy wells forming a cubic geometry in favour of the occupancy of carbon monoxide molecules, suggesting that the carbon monoxide-water and carbon monoxide-carbon monoxide interactions with adjacent cages provide a significant source of stability for the structure-II clathrate framework

Defective folate metabolism causes germline epigenetic instability and distinguishes Hira as a phenotype inheritance biomarker.

The mechanism behind transgenerational epigenetic inheritance is unclear, particularly through the maternal grandparental line. We previously showed that disruption of folate metabolism in mice by the Mtrr hypomorphic mutation results in transgenerational epigenetic inheritance of congenital malformations. Either maternal grandparent can initiate this phenomenon, which persists for at least four wildtype generations. Here, we use genome-wide approaches to reveal genetic stability in the Mtrr model and genome-wide differential DNA methylation in the germline of Mtrr mutant maternal grandfathers. We observe that, while epigenetic reprogramming occurs, wildtype grandprogeny and great grandprogeny exhibit transcriptional changes that correlate with germline methylation defects. One region encompasses the Hira gene, which is misexpressed in embryos for at least three wildtype generations in a manner that distinguishes Hira transcript expression as a biomarker of maternal phenotypic inheritance

Placental secretome characterization identifies candidates for pregnancy complications.

Alterations in maternal physiological adaptation during pregnancy lead to complications, including abnormal birthweight and gestational diabetes. Maternal adaptations are driven by placental hormones, although the full identity of these is lacking. This study unbiasedly characterized the secretory output of mouse placental endocrine cells and examined whether these data could identify placental hormones important for determining pregnancy outcome in humans. Secretome and cell peptidome analyses were performed on cultured primary trophoblast and fluorescence-activated sorted endocrine trophoblasts from mice and a placental secretome map was generated. Proteins secreted from the placenta were detectable in the circulation of mice and showed a higher relative abundance in pregnancy. Bioinformatic analyses showed that placental secretome proteins are involved in metabolic, immune and growth modulation, are largely expressed by human placenta and several are dysregulated in pregnancy complications. Moreover, proof-of-concept studies found that secreted placental proteins (sFLT1/MIF and ANGPT2/MIF ratios) were increased in women prior to diagnosis of gestational diabetes. Thus, placental secretome analysis could lead to the identification of new placental biomarkers of pregnancy complications

Real-World Assessment of Asthma Specialist Visits Among U.S. Patients with Severe Asthma.

BACKGROUND: U.S. guidelines recommend that patients with severe asthma be referred to specialists (allergists/immunologists or pulmonologists) for systematic assessment or comanagement; however, contemporary, real-world data on the frequency and impact of specialist care among U.S. severe asthma patients are lacking. OBJECTIVES: To quantify the frequency of asthma specialist visits among U.S. patients with severe asthma, identify patient demographic and clinical characteristics associated with specialist visits and describe health outcomes following specialist care. METHODS: Severe asthma patients aged 6 years or older were identified between January 1, 2015, and December 31, 2017, in the IQVIA PharMetrics® Plus database of commercially insured individuals, based on Healthcare Effectiveness Data and Information Set (HEDIS) criteria and Global Initiative for Asthma (GINA) step 4 or 5 treatment regimens. The frequency of asthma specialist (allergist/immunologist or pulmonologist) visits was described over 2 years. Patient characteristics associated with having 1 or more specialist visits were analyzed using multivariate regressions. Asthma exacerbations and health care resource utilization before and after specialist visit were compared. RESULTS: Of 54,332 patients identified, 38.2% had 1 or more specialist visits over 2 years. Patient characteristics predictive of specialist visits were asthma exacerbation frequency, younger age, and allergy/respiratory comorbidity burden (all P \u3c .001). Among patients with 1 or more specialist visits, a lower prevalence of asthma exacerbations and rescue inhaler use was observed following the first observed specialist visit. CONCLUSIONS: Specialist care was observed in fewer than half of U.S. patients with severe asthma and was least frequent among older adult patients and those with more nonrespiratory comorbidities. Increased specialist involvement in managing severe asthma may help improve care and patient outcomes

Defective folate metabolism causes germline epigenetic instability and distinguishes Hira as a phenotype inheritance biomarker

Funder: Center for Trophoblast ResearchAbstract: The mechanism behind transgenerational epigenetic inheritance is unclear, particularly through the maternal grandparental line. We previously showed that disruption of folate metabolism in mice by the Mtrr hypomorphic mutation results in transgenerational epigenetic inheritance of congenital malformations. Either maternal grandparent can initiate this phenomenon, which persists for at least four wildtype generations. Here, we use genome-wide approaches to reveal genetic stability in the Mtrr model and genome-wide differential DNA methylation in the germline of Mtrr mutant maternal grandfathers. We observe that, while epigenetic reprogramming occurs, wildtype grandprogeny and great grandprogeny exhibit transcriptional changes that correlate with germline methylation defects. One region encompasses the Hira gene, which is misexpressed in embryos for at least three wildtype generations in a manner that distinguishes Hira transcript expression as a biomarker of maternal phenotypic inheritance

Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients

Circulating tumor cells (CTCs) enter peripheral blood from primary tumors and seed metastases. The genome sequencing of CTCs could offer noninvasive prognosis or even diagnosis, but has been hampered by low single-cell genome coverage of scarce CTCs. Here, we report the use of the recently developed multiple annealing and looping-based amplification cycles for whole-genome amplification of single CTCs from lung cancer patients. We observed characteristic cancer-associated single-nucleotide variations and insertions/deletions in exomes of CTCs. These mutations provided information needed for individualized therapy, such as drug resistance and phenotypic transition, but were heterogeneous from cell to cell. In contrast, every CTC from an individual patient, regardless of the cancer subtypes, exhibited reproducible copy number variation (CNV) patterns, similar to those of the metastatic tumor of the same patient. Interestingly, different patients with the same lung cancer adenocarcinoma (ADC) shared similar CNV patterns in their CTCs. Even more interestingly, patients of small-cell lung cancer have CNV patterns distinctly different from those of ADC patients. Our finding suggests that CNVs at certain genomic loci are selected for the metastasis of cancer. The reproducibility of cancer-specific CNVs offers potential for CTC-based cancer diagnostics.Chemistry and Chemical Biolog