tbuckley/cabot-search huggingface dataset:
CircRNAs in cancer metabolism: a review
Authors: Tao Yu, Yanfen Wang, Yu Fan, Na Fang, Tongshan Wang, Tongpeng Xu, Yongqian Shu
Journal: Journal of Hematology & Oncology (2019)

Altered energy metabolism is a hallmark of tumors aiming at supplying necessary nutrients for tumorigenesis and development. These redirected metabolic pathways associated with carbohydrate, lipid and amino acid are orchestrated not only by carcinogenic proteins but by non-coding RNAs. Among them, circular RNA (circRNA), as a kind of novel identified non-coding RNAs, has become the focus of attention. Through binding with corresponding microRNAs or directly contacting proteins, circRNA plays a primarily important role in regulating cellular metabolism. Herein, we analyze the emerging findings and select circRNAs contributing to mutant glycolysis, lipogenesis and lipolysis, glutam inolysis, and oxidative respiration to deepen the understanding about the cancer metabolic regulatory network. In addition, we also discuss the possibility of circRNAs exerting their functions via exosomes and cancer stem cells. Owing to their unique structures and wide impacts, circRNAs may help reap huge fruits in developing clinical treatments targeting cancer metabolism.
Expression of mitochondrial membrane–linked SAB determines severity of sex-dependent acute liver injury
Authors: Sanda Win, Robert W.M. Min, Christopher Q. Chen, Jun Zhang, Yibu Chen, Meng Li, Ayako Suzuki, Manal F. Abdelmalek, Ying Wang, Mariam Aghajan, Filbert W.M. Aung, Anna Mae Diehl, Roger J. Davis, Tin A. Than, Neil Kaplowitz
Journal: Journal of Clinical Investigation (2019)

SH3 domain–binding protein that preferentially associates with Btk (SAB) is an outer-membrane docking protein for JNK-mediated impairment of mitochondrial function. Deletion of Sab in hepatocytes inhibits sustained JNK activation and cell death. The current study demonstrates that an increase in SAB expression enhanced the severity of acetaminophen-induced (APAP-induced) liver injury. Female mice were resistant to liver injury and exhibited markedly decreased hepatic SAB protein expression compared with male mice. The mechanism of SAB repression involved a pathway from ERα to p53 expression that induced miR34a-5p. miR34a-5p targeted the Sab mRNA coding region, thereby repressing SAB expression. Fulvestrant or p53 knockdown decreased miR34a-5p and increased SAB expression in female mice, leading to increased injury from APAP and TNF/galactosamine. In contrast, an ERα agonist increased p53 and miR34a-5p, which decreased SAB expression and hepatotoxicity in male mice. Hepatocyte-specific deletion of miR34a also increased the severity of liver injury in female mice, which was prevented by GalNAc-ASO knockdown of Sab. Similar to mice, premenopausal women expressed elevated levels of hepatic p53 and low levels of SAB, whereas age-matched men expressed low levels of p53 and high levels of SAB, but there was no difference in SAB expression between the sexes in the postmenopausal stage. In conclusion, SAB expression levels determined the severity of JNK-dependent liver injury. Female mice expressed low levels of hepatic SAB protein because of the ERα/p53/miR34a pathway, which repressed SAB expression and accounted for the resistance to liver injury seen in these females.
Association of Childhood History of Parental Incarceration and Juvenile Justice Involvement With Mental Health in Early Adulthood
Authors: Nia Heard-Garris, Kaitlyn Ann Sacotte, Tyler N. A. Winkelman, Alyssa Cohen, Patricia O. Ekwueme, Elizabeth Barnert, Mercedes Carnethon, Matthew M. Davis
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Young adults with a childhood history of parental incarceration (PI) or juvenile justice involvement (JJI) are more likely to have worse mental health outcomes than their peers. However, the association between mental health and exposure to both PI and JJI (PI plus JJI) is unclear. <h3>Objective</h3> To determine the association of PI plus JJI exposure with mental health outcomes in young adulthood. <h3>Design, Setting, and Participants</h3> A cross-sectional study of the US National Longitudinal Survey of Adolescent to Adult Health was conducted to examine the associations between PI, JJI, and PI plus JJI and mental health outcomes (ie, depression, anxiety, posttraumatic stress disorder, suicidal ideation, and mental health counseling). In-home interviews were conducted of 13 083 participants; 704 participants with PI after age 18 years were excluded, and 12 379 participants formed the analysis sample. Participants were in grades 7 to 12 in 1994 to 1995 and were ages 24 to 32 years at follow-up in 2008. Data analysis was completed in 2019. <h3>Exposures</h3> Parental incarceration, JJI, or PI plus JJI before age 18 years. <h3>Main Outcomes and Measures</h3> Mental health outcomes in early adulthood (ages 24-32 years). The analysis included multivariable logistic regression models; accounted for individual, family, and geographic-level factors; and generated adjusted odds ratios. <h3>Results</h3> Among 13 083 participants (6962 female; weighted proportion, 49.6%) with a mean age at wave 1 of 15.4 years (95% CI, 15.2-15.7 years), 10 499 (80.2%) did not have a history of PI or JJI, 1247 (9.1%) had childhood PI, 704 (5.2%) had PI after age 18 years, 492 (4.5%) had JJI only, and 141 (1.2%) had PI plus JJI. Sociodemographic characteristics varied by exposure. Exposure to both PI and JJI was associated with a greater risk of depression (adjusted odds ratio, 2.80; 95% CI, 1.60-4.90), anxiety (adjusted odds ratio, 1.89; 95% CI, 1.08-3.31), and posttraumatic stress disorder (adjusted odds ratio, 2.92; 95% CI, 1.09-7.82) compared with peers with neither exposure. Exposure to both PI and JJI did not have an additive association with mental health beyond PI or JJI alone. <h3>Conclusions and Relevance</h3> This study suggests that exposure to the criminal justice system during childhood places individuals at risk for poor mental health outcomes in early adulthood. Clinical, advocacy, and policy efforts that prioritize reducing the impact of the US criminal justice system on children may yield substantive improvements in the mental well-being of those individuals as adults.
P14.117 Cost efficient test algorithm for molecular subgrouping of medulloblastomas for day-to-day practice in resource limited countries
Authors: K Kaur, P Jha, P Pathak, V Suri, M C Sharma, A Garg, A Suri, C Sarkar
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Molecular classification of medulloblastomas(MB) is prognostically and therapeutically relevant and helps in better risk-stratification. Translation of this subgrouping to routine practice still remains a challenge. The most pathologist-accessible techniques for molecular subgrouping include immunohistochemistry(IHC), fluorescent in-situ hybridization(FISH) and Nanostring assay. Objectives:(1)Molecular subgrouping of MBs by IHC and FISH, and Nanostring Assay (2)To compare their efficacy against sequencing and DNA methylation, and cost for applicability in resource-constrained centers METHODS Ninety-five cases of MB with adequate tissue were included. Molecular subgrouping was performed by IHC for β-catenin, GAB1, YAP1, and p53; FISH for MYC amplification, and sequencing for CTNNB1, and by Nanostring Assay on the same set of MBs. Further, a subset of cases were subjected to 850k DNA methylation array. RESULTS IHC+FISH classified MBs into 15.8% WNT, 16.8% SHH, and 67.4% non-WNT/non-SHH subgroups; with MYC amplification identified in 20.3% cases of non-WNT/non-SHH. A single showed diffuse strong p53 positivity among the SHH subgroup. Nanostring successfully classified 91.5% MBs into 25.3% WNT, 17.2% SHH, 23% Group3 and 34.5% Group4. However, Nanostring assay failure was seen in eight cases, all of which were &gt;8-years-old formalin-fixed paraffin-embedded tissue blocks. Concordant subgroup assignment was noted in 88.5% cases, while subgroup switching was seen in 11.5% cases. Both methods showed prognostic correlation. Among the 5 discrepant cases, which switched to WNT subgroup by Nanostring, only 2 were found to have CTNNB1 mutation. Methylation profiling performed on discordant cases revealed 1 out of 4 extra WNT identified by Nanostring to be WNT, others aligned with IHC subgroups; extra SHH by Nanostring turned out to be SHH by methylation. CONCLUSIONS Both IHC supplemented by FISH and Nanostring are robust methods for molecular subgrouping, albeit with few disadvantages. IHC cannot differentiate between Groups 3 and 4, while Nanostring cannot classify older-archived tumors, and is not available at most centres. WNT subgroup with the best prognosis is best detected by IHC or IHC followed by sequencing for confirmation. Nanostring Assay is better suitable to separate Group 3, the worst prognostic group from Group 4. Thus, both the methods complement each other and can be used in concert for high confidence allotment of molecular subgroups in clinical practice. The cost of IHC plus Nanostring will almost be the same as IHC plus FISH. We recommend a cost-efficient algorithmic approach using histopathological subtype and IHC as the first step followed by Nanostring or FISH, wherever suitable.
Carcinomas in the children and young adults: A report form Children’s Oncology Group APEC14B1 study.
Authors: Rajkumar Venkatramani, Jin Piao, Mark D. Krailo, Carlos Rodriguez-Galindo, Farzana D. Pashankar
Journal: Journal of Clinical Oncology (2019)

e21505 Background: Carcinomas are rare in the children and young adults. Systematic study of epidemiology and biology of carcinomas in this age group is lacking. Project:EveryChild, A Registry, Eligibility Screening, Biology and Outcome Study (APEC14B1) aims to collect demographic and epidemiologic information of every child and young adult diagnosed with cancer in Children’s Oncology Group institutions. It also serves as a biobank for tumor and biological tissue collected from cancer patients and their parents. Methods: We analyzed the clinical and demographic characteristics of patients with the following diagnosis enrolled in the APEC14B1 study: Thyroid cancer, adrenocortical cancer, colorectal cancer, nasopharyngeal carcinoma, and any other carcinoma. Patients with renal cell carcinoma were not included. Results: Between December 2015 and October 2018, 120 patients with carcinomas were enrolled; thyroid (n = 42, 35.0%), nasopharyngeal (n = 22, 18.3%), colorectal (n = 7, 5.8%), adrenocortical (n = 3, 2.5 %), and others (n = 46, 38.3%). Majority were female (n = 74, 61.7%), mainly due to female predominance (31/42, 73.8%) in thyroid cancer. Majority were white race (n = 81, 67.5 %) and not Hispanic (n = 89, 74.2%). Two patients were enrolled in 2015, 24 in 2016, 47 in 2017, and 47 in 2018. The median age at diagnosis was 15.6 years (range 0.5- 24.6 years). Lymph node involvement was reported in 92 patients and was positive in 58 (63.0%). Metastasis status was reported in 108 and 29 (26.8%) patients had distant metastases. Seventy eight percent (n = 94) of patients agreed to banking of biological material for future research and 90% agreed to be contacted in future for other research studies. Biological samples were banked from 46 patients (48.9%) including tissue submissions from 39 patients, blood submissions from 21 patients and serum submissions from 5 patients. Conclusions: APEC14B1 study was successful in enrolling a large number of children and young adults with carcinomas in a short period of time. Lymph node and distant metastases were common in children and young adults with carcinomas. The enrollment of patients with carcinomas will likely accelerate in the coming years as more institutions open the study. This study will serve as an important resource for investigators interested in clinical and biological research of carcinomas which occur in children and young adults.
Association Between Data Sources and US Food and Drug Administration Drug Safety Communications
Authors: Noam Tau, Tzippy Shochat, Anat Gafter-Gvili, Ariadna Tibau, Eitan Amir, Daniel Shepshelovich
Journal: JAMA Internal Medicine (2019)

This study describes sources of initial safety signals that that preceded US Food and Drug Administration (FDA) drug safety communications and examines their associations with drug characteristics and subsequent label changes.
Evolutionary History of GLIS Genes Illuminates Their Roles in Cell Reprograming and Ciliogenesis
Authors: Yuuri Yasuoka, Masahito Matsumoto, Ken Yagi, Yasushi Okazaki
Journal: Molecular Biology and Evolution (2019)

The GLIS family transcription factors, GLIS1 and GLIS3, potentiate generation of induced pluripotent stem cells (iPSCs). In contrast, another GLIS family member, GLIS2, suppresses cell reprograming. To understand how these disparate roles arose, we examined evolutionary origins and genomic organization of GLIS genes. Comprehensive phylogenetic analysis shows that GLIS1 and GLIS3 originated during vertebrate whole genome duplication, whereas GLIS2 is a sister group to the GLIS1/3 and GLI families. This result is consistent with their opposing functions in cell reprograming. Glis1 evolved faster than Glis3, losing many protein-interacting motifs. This suggests that Glis1 acquired new functions under weakened evolutionary constraints. In fact, GLIS1 induces induced pluripotent stem cells more strongly. Transcriptomic data from various animal embryos demonstrate that glis1 is maternally expressed in some tetrapods, whereas vertebrate glis3 and invertebrate glis1/3 genes are rarely expressed in oocytes, suggesting that vertebrate (or tetrapod) Glis1 acquired a new expression domain and function as a maternal factor. Furthermore, comparative genomic analysis reveals that glis1/3 is part of a bilaterian-specific gene cluster, together with rfx3, ndc1, hspb11, and lrrc42. Because known functions of these genes are related to cilia formation and function, the last common ancestor of bilaterians may have acquired this cluster by shuffling gene order to establish more sophisticated epithelial tissues involving cilia. This evolutionary study highlights the significance of GLIS1/3 for cell reprograming, development, and diseases in ciliated organs such as lung, kidney, and pancreas.
Germline DDX41 mutations define a significant entity within adult MDS/AML patients
Authors: Marie Sébert, Marie Passet, Anna Raimbault, Ramy Rahmé, Emmanuel Raffoux, Flore Sicre de Fontbrune, Marco Cerrano, Samuel Quentin, Nadia Vasquez, Mélanie Da Costa, Nicolas Boissel, Hervé Dombret, Régis Peffault de Latour, Gérard Socié, Raphaël Itzykson, Pierre Fenaux, Jean Soulier, Lionel Adès, Emmanuelle Clappier
Journal: Blood (2019)
Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies
Authors: A.B. Kimball, K.A. Papp, K. Reich, M. Gooderham, Q. Li, N. Cichanowitz, C. La Rosa, A. Blauvelt
Journal: British Journal of Dermatology (2019)

Chronic psoriasis may require medication adjustments over time. To evaluate the efficacy/safety of tildrakizumab in subgroups from the reSURFACE studies (N = 1862) that received continuous dosing, higher/lower dosing, treatment interruption/reinitiation and initiation. Responders [Psoriasis Area and Severity Index (PASI) ≥ 75%] and partial responders (PASI ≥ 50% to < 75%) in Part 3 of the reSURFACE studies (weeks 28–52 or week 64) who received tildrakizumab 200 mg or 100 mg were rerandomized to the same dosage (T100/T100 or T200/T200), a higher/lower dosage (T100/T200 or T200/T100) or placebo (PBO) (T100/PBO or T200/PBO). Patients receiving PBO who relapsed were reinitiated to tildrakizumab. Etanercept (ETN) week‐28 partial responders and nonresponders (PASI < 50%) received tildrakizumab 200 mg (ETN/T200). Among T100/T100 and T200/T200 week‐28 partial responders, the proportion of patients who achieved as‐observed PASI 75 responses increased over time. Among T100/T200 week‐28 partial responders, PASI 75 responses increased from week 32 (38·5%) to week 52 (63·2%) and remained consistent in T200/T100 week‐28 responders. Among patients who relapsed in the T100/PBO and T200/PBO groups, 86% and 83% of those who reinitiated tildrakizumab achieved PASI 75 by week 64, respectively. Among ETN/T200 week‐28 partial responders, PASI 75 responses (nonresponder imputation) increased from week 32 (24·1%) to week 52 (74·7%). PASI 90, PASI 100 and Physician's Global Assessment responses were consistent with PASI 75 results. Treatment was well tolerated. Patients generally fared well with tildrakizumab maintenance, reinitiation, dose adjustment or initiation. What's already known about this topic? Tildrakizumab demonstrated significant efficacy vs. placebo with a positive safety profile during the first 28 weeks of treatment in two randomized double‐blind trials. What does this study add? Treatment scenarios with tildrakizumab, such as long‐term continuous dosing (up to 64 weeks), treatment interruption/reinitiation and switching from another biologic, can be part of the management of plaque psoriasis with a reasonable expectation of efficacy and tolerability.
Does disallowing body checking in non-elite 13- to 14-year-old ice hockey leagues reduce rates of injury and concussion? A cohort study in two Canadian provinces
Authors: Carolyn Emery, Jean-Michel Galarneau, Luz Palacios-Derflingher, Amanda Marie Black, Paul Eliason, Maciek Krolikowski, Nicole Spencer, Stacy Kozak, Kathryn J Schneider, Shelina Babul, Martin Mrazik, Constance M Lebrun, Claude Goulet, Alison Macpherson, Brent E Hagel
Journal: British Journal of Sports Medicine (2019)

Objective To compare rates of injury and concussion among non-elite (lowest 60% by division of play) Bantam (ages 13–14 years) ice hockey leagues that disallow body checking to non-elite Bantam leagues that allow body checking. Methods In this 2-year cohort study, Bantam non-elite ice hockey players were recruited from leagues where policy allowed body checking in games (Calgary/Edmonton 2014–2015, Edmonton 2015–2016) and where policy disallowed body checking (Kelowna/Vancouver 2014–2015, Calgary 2015–2016). All ice hockey game-related injuries resulting in medical attention, inability to complete a session and/or time loss from hockey were identified using valid injury surveillance methodology. Any player suspected of having concussion was referred to a study physician for diagnosis and management. Results 49 body checking (608 players) and 33 non-body checking teams (396 players) participated. There were 129 injuries (incidence rate (IR)=5.52/1000 hours) and 54 concussions (IR=2.31/1000 hours) in the body checking teams in games. After policy change, there were 31 injuries (IR=2.50/1000 hours) and 17 concussions (IR=1.37/1000 hours) in games. Policy disallowing body checking was associated with a lower rate of all injury (adjusted incidence rate ratio (IRR)=0.45; 95% CI: 0.27 to 0.76). The point estimate showed a lower rate of concussion (adjusted IRR=0.59; 95% CI: 0.30 to 1.17), but this was not statistically significant. Conclusion Policy change disallowing body checking in non-elite Bantam ice hockey resulted in a 55% lower rate of injury. There is growing evidence that disallowing body checking in youth ice hockey is associated with fewer injuries.
Radiation-Induced Sarcoma on 18F-FDG PET/CT After Treatment of Gorham-Stout Disease of the Maxilla
Authors: Jose R. Rodriguez-Vazquez, Srinivasa R. Chandra, Megan E. Albertson, Neil J. Hansen, Craig M. Johnson
Journal: Clinical Nuclear Medicine (2019)

Gorham-Stout disease is a rare disorder characterized by proliferation of lymphatic and vascular channels within bone resulting in osteolysis. A 53-year-old man with Gorham-Stout disease involving the left maxilla underwent previous treatment including radiation therapy and intralesional chemotherapeutic injections. He later presented with anemia, facial pain, weight loss, and nasal cavity hemorrhage. CT imaging demonstrated a mass centered within the right maxillary sinus with locoregional involvement. PET/CT showed prominent FDG activity involving the mass centered in the right maxillary sinus with low-grade avidity involving the contralateral maxilla in regions of treated Gorham-Stout disease. Biopsy of the mass confirmed radiation-induced sarcoma.
The MicroRNA-92a/Sp1/MyoD Axis Regulates Hypoxic Stimulation of Myogenic Lineage Differentiation in Mouse Embryonic Stem Cells
Authors: Seo-Yeon Lee, Jimin Yang, Jung Hwa Park, Hwa Kyoung Shin, Woo Jean Kim, Su-Yeon Kim, Eun Ju Lee, Injoo Hwang, Choon-Soo Lee, Jaewon Lee, Hyo-Soo Kim
Journal: Molecular Therapy (2019)

Hypoxic microenvironments exist in developing embryonic tissues and determine stem cell fate. We previously demonstrated that hypoxic priming plays roles in lineage commitment of embryonic stem cells. In the present study, we found that hypoxia-primed embryoid bodies (Hyp-EBs) efficiently differentiate into the myogenic lineage, resulting in the induction of the myogenic marker MyoD, which was not mediated by hypoxia-inducible factor 1α (HIF1α) or HIF2α, but rather by Sp1 induction and binding to the MyoD promoter. Knockdown of Sp1 in Hyp-EBs abrogated hypoxia-induced MyoD expression and myogenic differentiation. Importantly, in the cardiotoxin-muscle injury mice model, Hyp-EB transplantation facilitated muscle regeneration in vivo, whereas transplantation of Sp1-knockdown Hyp-EBs failed to do. Moreover, we compared microRNA (miRNA) expression profiles between EBs under normoxia versus hypoxia and found that hypoxia-mediated Sp1 induction was mediated by the suppression of miRNA-92a, which directly targeted the 3′ untranslated region (3′ UTR) of Sp1. Further, the inhibitory effect of miRNA-92a on Sp1 in luciferase assay was abolished by a point mutation in specific sequence in the Sp1 3′ UTR that is required for the binding of miRNA-92a. Collectively, these results suggest that hypoxic priming enhances EB commitment to the myogenic lineage through miR-92a/Sp1/MyoD regulatory axis, suggesting a new pathway that promotes myogenic-lineage differentiation.Graphical abstract
Tissue Engineering: Self‐Assembling Peptide Hydrogel Matrices Improve the Neurotrophic Potential of Human Adipose‐Derived Stem Cells (Adv. Healthcare Mater. 17/2019)
Authors: Alessandro Faroni, Victoria L. Workman, Alberto Saiani, Adam J. Reid
Journal: Advanced Healthcare Materials (2019)

In article number 1900410 by Alessandro Faroni and co-workers, human adipose-derived stem cells (hASC) can be differentiated toward a neurotrophic phenotype (hdASC) by chemical stimulation. The differentiation causes up/downregulation of key neuroglial genes. In this study, hdASC are plated with PeptiGel-Alpha1 and Alpha2 substrates, as well as Col I, and the expression levels of differentiation genes is assessed.