tbuckley/cabot-search huggingface dataset:
Implementation and evaluation of clinical exome sequencing in childhood cancer care: The BASIC<sup>3</sup> study.
Authors: Donald W. Parsons, Murali M. Chintagumpala, Stacey L. Berg, Dolores H. López-Terrada, Angshumoy Roy, Robin A. Kerstein, Sarah Scollon, Susan G. Hilsenbeck, Uma Ramamurthy, Christine M. Eng, Yaping Yang, Richard A. Gibbs, David A. Wheeler, Richard L. Street, Laurence B. McCullough, Amy L. McGuire, Federico A. Monzon, Sharon E. Plon
Journal: Journal of Clinical Oncology (2013)

10023 Background: Advances in sequencing technologies allow for provision of genome-scale data to oncologists and geneticists caring for pediatric cancer patients. The goal of the BASIC 3 (Baylor Advancing Sequencing into Childhood Cancer Care) study is to determine the clinical impact of incorporating CLIA-certified tumor and constitutional exome sequencing into the care of children with newly diagnosed solid tumors. Methods: Blood and frozen tumor samples obtained at initial surgery are submitted for clinical exome sequencing (target enrollment 280 patients). Results are deposited into the electronic medical record and disclosed to families by their oncologist and a genetic counselor. Identification of germline cancer susceptibility mutations is compared with standard testing practices. Oncologists are surveyed on prioritization of treatment options in the hypothetical event of tumor recurrence before and after receiving tumor exome results. Patients will be followed for two years to assess the clinical utility of exome data. Preferences for reporting this complex information are obtained by interviews and audiorecording of disclosure visits. Results: Initial results reveal that41 of 49 (84%) ethnically diverse families have consented to enroll on study. Adequate tumor samples were available from 35 of 41 patients (85%), including 11 of 15 (73%) patients with CNS tumors and 24 of 26 (92%) with non-CNS tumors. Pathogenic germline cancer susceptibility mutations (TP53, MSH2) were reported in 2 of the first 11 patients, with a medically-actionable mutation in a gene (SCN5A) unrelated to cancer in 1 patient and 0-4 (median of 2) recessive carrier mutations per patient. Between 9 and 33 protein altering mutations (median of 11) have been identified in tumors, including known cancer genes such as TP53 and others with no known link to pediatric cancer. Conclusions: A robust clinical pipeline for exome sequencing of blood and tumor samples has been successfully developed with significant parental interest. Data assessing the clinical utility of both the tumor and constitutional exomes and the preferences of oncologists and parents for reporting of these results are under study. Supported by NHGRI 1U01HG006485.
Do we need to Measure the Vision of Children?
Authors: A R Fielder, M J Moseley
Journal: Journal of the Royal Society of Medicine (1988)

With the advent of the acuity card procedure, it is now possible to measure quantitatively the vision of infants and young children in a routine clinical setting. Over a 19 month period 1177 tests were performed on 586 patients; ages ranged from 0.5 weeks to 23 years. Overall 1102 (93%) were successful, as were 588 of the 627 (94%) tests performed on children under the age of two years when no conventional acuity test is possible. The results serve as a background on which the argument for and against the need to measure the vision of children is considered.
Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma
Authors: Sylvie Job, Delphine Rapoud, Alexandre Dos Santos, Patrick Gonzalez, Christophe Desterke, Gérard Pascal, Nabila Elarouci, Mira Ayadi, René Adam, Daniel Azoulay, Denis Castaing, Eric Vibert, Daniel Cherqui, Didier Samuel, Antonio Sa Cuhna, Agnès Marchio, Pascal Pineau, Catherine Guettier, Aurélien de Reyniès, Jamila Faivre
Journal: Hepatology (2019)

Intrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of the desmoplastic tumor microenvironment (TME) of ICC has been stressed but was insufficiently taken into account in the search for classifications of ICC adapted to clinical trial design. We investigated the heterogeneous tumor stroma composition and built a TME-based classification of ICC tumors that detects potentially targetable ICC subtypes.We established the bulk gene expression profiles of 78 ICCs. Epithelial and stromal compartments of 23 ICCs were laser microdissected. We quantified 14 gene expression signatures of the TME and those of 3 functional indicators (liver activity, inflammation, immune resistance). The cell population abundances were quantified using the microenvironment cell population-counter package and compared with immunohistochemistry. We performed an unsupervised TME-based classification of 198 ICCs (training set) and 368 ICCs (validation set). We determined immune response and signaling features of the different immune subtypes by functional annotations. We showed that a set of 198 ICCs could be classified into 4 TME-based subtypes related to distinct immune escape mechanisms and patient outcomes. The validity of these immune subtypes was confirmed over an independent set of 368 ICCs and by immunohistochemical analysis of 64 ICC tissue samples. About 45% of ICCs displayed an immune desert phenotype. The other subtypes differed in nature (lymphoid, myeloid, mesenchymal) and abundance of tumor-infiltrating cells. The inflamed subtype (11%) presented a massive T lymphocyte infiltration, an activation of inflammatory and immune checkpoint pathways, and was associated with the longest patient survival.We showed the existence of an inflamed ICC subtype, which is potentially treatable with checkpoint blockade immunotherapy.
Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration
Authors: Nadia Cobo-Vuilleumier, Benoit R. Gauthier
Journal: Metabolism (2020)

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that targets the destruction of islet beta-cells resulting in insulin deficiency, hyperglycemia and death if untreated. Despite advances in medical devices and longer-acting insulin, there is still no robust therapy to substitute and protect beta-cells that are lost in T1DM. Attempts to refrain from the autoimmune attack have failed to achieve glycemic control in patients highlighting the necessity for a paradigm shift in T1DM treatment. Paradoxically, beta-cells are present in T1DM patients indicating a disturbed equilibrium between the immune attack and beta-cell regeneration reminiscent of unresolved wound healing that under normal circumstances progression towards an anti-inflammatory milieu promotes regeneration. Thus, the ultimate T1DM therapy should concomitantly restore immune self-tolerance and replenish the beta-cell mass similar to wound healing. Recently the agonistic activation of the nuclear receptor LRH-1/NR5A2 was shown to induce immune self-tolerance, increase beta-cell survival and promote regeneration through a mechanism of alpha-to-beta cell phenotypic switch. This trans-regeneration process appears to be facilitated by a pancreatic anti-inflammatory environment induced by LRH-1/NR5A2 activation. Herein, we review the literature on the role of LRH1/NR5A2 in immunity and islet physiology and propose that a cross-talk between these cellular compartments is mandatory to achieve therapeutic benefits.
Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis
Authors: Takashi Namba, Judit Dóczi, Anneline Pinson, Lei Xing, Nereo Kalebic, Michaela Wilsch-Bräuninger, Katherine R. Long, Samir Vaid, Janelle Lauer, Aliona Bogdanova, Barbara Borgonovo, Anna Shevchenko, Patrick Keller, David Drechsel, Teymuras Kurzchalia, Pauline Wimberger, Christos Chinopoulos, Wieland B. Huttner
Journal: Neuron (2019)
5-Nitroimidazole refractory giardiasis is common in Matanzas, Cuba and effectively treated by secnidazole plus high-dose mebendazole or quinacrine: a prospective observational cohort study
Authors: R. Cañete, A.L. Noda, M. Rodríguez, K. Brito, E. Herrera, P.-E. Kofoed, J. Ursing
Journal: Clinical Microbiology and Infection (2020)
Graft-Versus-Host Disease Causes the Failure of Donor Hematopoietic Progenitor Cells to Reconstitute Plasmacytoid Dendritic Cells That Promote Tolerance of Donor T Cells Against the Host
Authors: Yuanyuan Tian, Lijun Meng, Hongshuang Yu, Ying Wang, Tien Bui, Shin Mineishi, Hong Zheng, Stefania Gallucci, Yanyun Zhang, Shaoyan Hu, Yi Zhang
Journal: Blood (2019)
Episodic memory is emotionally laden memory, requiring amygdala involvement
Authors: Angelica Staniloiu, Hans J. Markowitsch
Journal: Behavioral and Brain Sciences (2019)

Abstract The memory impairment of neurological and psychiatric patients is seen as occurring mainly in the autobiographical-episodic memory domain and this is considered to depend on limbic structures such as the amygdala or the septal nuclei. Especially the amygdala is a hub for giving an emotional flavor to personal memories. Bastin et al. fail to include the amygdala in their integrative memory model.
More than 50% of hip replacements seem to last 25 years
Authors: Rob Cook, Peter Davidson, Rosie Martin
Journal: BMJ (2019)

The studyHow long does a hip replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-upEvans JT, Evans JP, Walker R, Blom AW, Whitehouse MR, Sayers APublished on 16 February 2019 Lancet 2019;393:647-54This study was supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000781/more-than-50-of-hip-replacements-appear-to-last-25-years.
Photodynamic cancer therapy enhances accumulation of nanoparticles in tumor-associated myeloid cells
Authors: Ruben V. Huis in 't Veld, Laila Ritsma, Jan Willem Kleinovink, Ivo Que, Ferry Ossendorp, Luis J. Cruz
Journal: Journal of Controlled Release (2019)

In cancer treatment, nanomedicines may be employed in an attempt to improve the tumor localization of antineoplastic drugs e.g. immunotherapeutic agents either through passive or active targeting, thereby potentially enhancing therapeutic effect and reducing undesired off-target effects. However, a large number of administrated nanocarriers often fail to reach the tumor area. In the present study, we show that photodynamic therapy (PDT) enhances the tumor accumulation of systemically administered lipid-PEG layer coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). Intravital microscopy and histological analysis of the tumor area reveal that the tumor vasculature was disrupted after PDT, disturbing blood flow and coinciding with entrapment of nanocarriers in the tumor area. We observed that the nanoparticles accumulating after treatment do not confine to specific locations within the tumor, but rather localize to various cells present throughout the tumor area. Finally, we show by flow cytometry that NP accumulation occurred mostly in immune cells of the myeloid lineage present in the tumor microenvironment (TME) as well as in tumor cells, albeit to a lower extent. These data expose opportunities for combination treatments of clinical PDT with NP-based immunotherapy to modulate the TME and improve antitumor immune responses.
Contradictory iPledge Requirements Hinder Physician Practice and Patient Care
Authors: Bobak T. Pousti, Nicholas K. Mollanazar
Journal: JAMA Dermatology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Abstract 15229: Critical Protective Role of Endogenous Nitric Oxide in Established Severe Pulmonary Arterial Hypertension in Rats
Authors: Mariko Tanaka, Kohtaro Abe, Masahiko Oka, Daryl O Schwenke, Mikiyasu Shirai, Ichiro Kuwahira, Yoshitaka Hirooka, Sumio Hoka, Kenji Sunagawa
Journal: Circulation (2015)

Background: It is widely believed that impared bioavailability of endothelium-derived nitric oxide (NO) contributes to the development of pulmonary arterial hypertension (PAH). However, there are reports that show high pulmonary endothelial NO synthase (eNOS) expression in PAH patients, and the functional roles of endogenous NO in established PAH remain unclear. Hypothesis: We tested the hypothesis that pulmonary eNOS expression is increased, and that endogenous NO plays an important functional role in a rat model of PAH. Method and Results: Adult male Sprague Dawley rats (BW: 150 - 200g) were injected subcutaneously with Sugen5416 (20 mg/kg; VEGF receptor blocker), and exposed to hypoxia (10% O2) for 3 weeks followed by a return to normoxia for 5 weeks. Hemodynamic examination was performed at the 1-, 3-, 5- and 8-week (wk) time points after Sugen5416 injection. RV systolic pressure increased time-dependently (RVSP: 47 ± 6, 83 ± 14, 101 ± 22, and 122 ± 16 mmHg at 1-, 3-, 5- and 8-wk time points, n=4-6) compared with normal rats (31 ± 2 mmHg, n=4, p&lt;0.01, respectively). Blockade of NOS with Nω-nitro-L- arginine methyl ester (L-NAME, 30 mg/kg, iv) further increased RVSP acutely (ΔRVSP from each baseline: 7 ± 11, 25 ± 11, 52± 21, and 43 ± 13 at 1-, 3-, 5- and 8-wk time points) compared with normal rats (0.8 ± 1.1 mmHg). At the 8-wk time point, inhibition of NOS caused a marked RVSP elevation (165 ± 11 mmHg), leading to RV failure and death in all rats tested. In vivo pulmonary angiogram using the synchrotron radiation microangiogram system showed severe small pulmonary arterial narrowing in response to L-NAME. Western blot analysis showed increased eNOS protein levels in PAH rat lungs (n=4 each time point; p&lt;0.01 vs. normal) and immunohistochemisty revealed high expression of eNOS in remodeled pulmonary arteries at the 5- and 8-time points. Conclusion: Based on our findings that L-NAME caused marked pulmonary vasoconstriction and further elevation in RVSP and that there was high lung eNOS protein levels in advanced PAH rats, we conclude, contrary to the general assumption, that endogenous NO presumably via eNOS may play a critical protective role by counteracting severe pulmonary vasoconstriction in established PAH.
Genomics of lethal prostate cancer at diagnosis and castration resistance
Authors: Joaquin Mateo, George Seed, Claudia Bertan, Pasquale Rescigno, David Dolling, Ines Figueiredo, Susana Miranda, Daniel Nava Rodrigues, Bora Gurel, Matthew Clarke, Mark Atkin, Rob Chandler, Carlo Messina, Semini Sumanasuriya, Diletta Bianchini, Maialen Barrero, Antonella Petermolo, Zafeiris Zafeiriou, Mariane Fontes, Raquel Perez-Lopez, Nina Tunariu, Ben Fulton, Robert Jones, Ursula McGovern, Christy Ralph, Mohini Varughese, Omi Parikh, Suneil Jain, Tony Elliott, Shahneen Sandhu, Nuria Porta, Emma Hall, Wei Yuan, Suzanne Carreira, Johann S. de Bono
Journal: Journal of Clinical Investigation (2019)

The genomics of primary prostate cancer differ from those of metastatic castration-resistant prostate cancer (mCRPC). We studied genomic aberrations in primary prostate cancer biopsies from patients who developed mCRPC, also studying matching, same-patient, diagnostic, and mCRPC biopsies following treatment. We profiled 470 treatment-naive prostate cancer diagnostic biopsies and, for 61 cases, mCRPC biopsies, using targeted and low-pass whole-genome sequencing (n = 52). Descriptive statistics were used to summarize mutation and copy number profile. Prevalence was compared using Fisher's exact test. Survival correlations were studied using log-rank test. TP53 (27%) and PTEN (12%) and DDR gene defects (BRCA2 7%; CDK12 5%; ATM 4%) were commonly detected. TP53, BRCA2, and CDK12 mutations were markedly more common than described in the TCGA cohort. Patients with RB1 loss in the primary tumor had a worse prognosis. Among 61 men with matched hormone-naive and mCRPC biopsies, differences were identified in AR, TP53, RB1, and PI3K/AKT mutational status between same-patient samples. In conclusion, the genomics of diagnostic prostatic biopsies acquired from men who develop mCRPC differ from those of the nonlethal primary prostatic cancers. RB1/TP53/AR aberrations are enriched in later stages, but the prevalence of DDR defects in diagnostic samples is similar to mCRPC.
Targeted Inhibition of the Epidermal Growth Factor Receptor and Mammalian Target of Rapamycin Signaling Pathways in Olmsted Syndrome
Authors: April Zhang, Sabine Duchatelet, Nikita Lakdawala, Richard L. Tower, Carrie Diamond, Kalyani Marathe, India Hill, Gabriele Richard, Yaser Diab, Anna Yasmine Kirkorian, Flora Watanabe, Dawn H. Siegel, Alain Hovnanian
Journal: JAMA Dermatology (2020)

Olmsted syndrome is a rare and disabling genodermatosis for which no successful treatment is currently available.To evaluate the clinical response to the mammalian target of rapamycin (mTOR) inhibitor sirolimus and/or the epidermal growth factor receptor (EGFR) inhibitor erlotinib among patients with Olmsted syndrome.This case series focused on 4 children with treatment-refractory Olmsted syndrome. These children received treatments (initiated in 2017 and 2018) at the outpatient dermatology clinic at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin; Children's National Hospital in Washington, DC; and Hospital Infantil Pequeno Príncipe, Curitiba in Paraná, Brazil.Immunohistochemical analyses for mTOR and EGFR activation were performed on skin biopsy specimens from 2 patients. Oral sirolimus was administered to these 2 patients at a dosage of 0.8 mg/m2 twice daily, titrated to a goal trough whole-blood concentration of 10 to 15 ng/mL. Erlotinib was administered to all 4 patients at a dosage of 2 mg/kg/d.Clinical responses were assessed with visual analog scales for pruritus and pain and/or the Children's Dermatology Life Quality Index. Adverse effects were monitored throughout treatment.Four patients (mean [SD] age, 7 [6] years; 2 boys and 2 girls) were analyzed. Lesional skin immunostaining showed increased phosphorylated ribosomal protein S6 (RPS6) and phosphorylated EGFR staining in the epidermis, indicating enhanced mTOR and EGFR signaling activation. Patients 1 and 2 were initially treated with sirolimus, displaying substantial clinical improvement in erythema and periorificial hyperkeratosis afterward. When switched to erlotinib, these patients showed substantial palmoplantar keratoderma (PPK) improvement. Patients 3 and 4 were treated with erlotinib only and later showed rapid and near complete resolution of PPK and substantial improvement in Children's Dermatology Life Quality Index scores. All 4 patients had sustained improvements in pruritus and pain. No severe adverse effects were reported.This study's findings suggest that the EGFR-mTOR cascade may play a substantial role in the pathophysiological process of Olmsted syndrome and may serve as a major therapeutic target. Oral sirolimus and erlotinib may be a promising, life-altering treatment for pediatric patients with Olmsted syndrome.
ROS-responsive polyurethane fibrous patches loaded with methylprednisolone (MP) for restoring structures and functions of infarcted myocardium in vivo
Authors: Yuejun Yao, Jie Ding, Zhaoyi Wang, Haolan Zhang, Jieqi Xie, Yingchao Wang, Liangjie Hong, Zhengwei Mao, Jianqing Gao, Changyou Gao
Journal: Biomaterials (2019)
一项关于在化脓性汗腺炎研究中使用词语“加剧”的回顾
Authors: J.S. Kirby, B. Moore, P. Leiphart, K. Shumaker, A. Mammis-Gierbolini, F. Benhadou, V. del Marmol
Journal: British Journal of Dermatology (2020)

化脓性汗腺炎 (HS) 可导致皮肤发红、疼痛、排液性肿块和隧道样。在美国和欧洲约 0.1% 至 1% 的患者患有 HS。HS 在女性中更为常见。HS 病灶(受影响部位)大多数发生在身体褶皱处, 如腋窝、乳房下面、腹股沟或臀部。 病灶可能出现后消失或持续数月或数年。HS 可能出现多次,而且比平时更糟糕。这种情况称为“加剧”。为在未来研究中衡量加剧状况, 需要对加剧进行定义。 这项研究旨在了解过去研究中如何定义加剧。研究人员研究了关于提及词语“加剧”或“加重”的 HS 研究的已发表文章的数据库。研究人员发现 274 项已发表的研究, 其中 154 项研究适合纳入本研究。 27 项研究提及词语“加剧”, 16 项包括词语“加重”。只有 2 项研究包括“加剧”一词的定义, 只有一篇论文包括“加重”一词的定义。衡量加剧(或加重)的方法是凭借患者的经验或临床医生对皮肤的检查。 这项回顾研究表明, HS 加剧通常不会在研究中定义, 而且定义并不总是一样。需要更好地定义 HS 加剧, 以便 HS 患者、临床医生和研究人员能够更好地衡量 HS 的活动以及治疗的影响。 This summary relates to the study: 对化脓性汗腺炎“加剧”定义的叙述性回顾
Alcohol Abstinence in Drinkers with Atrial Fibrillation
Authors: Aleksandr Voskoboinik, Jonathan M. Kalman, Anurika De Silva, Thomas Nicholls, Benedict Costello, Shane Nanayakkara, Sandeep Prabhu, Dion Stub, Sonia Azzopardi, Donna Vizi, Geoffrey Wong, Chrishan Nalliah, Hariharan Sugumar, Michael Wong, Emily Kotschet, David Kaye, Andrew J. Taylor, Peter M. Kistler
Journal: New England Journal of Medicine (2020)

Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear.We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline were randomly assigned in a 1:1 ratio to either abstain from alcohol or continue their usual alcohol consumption. The two primary end points were freedom from recurrence of atrial fibrillation (after a 2-week "blanking period") and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up.Of 140 patients who underwent randomization (85% men; mean [±SD] age, 62±9 years), 70 were assigned to the abstinence group and 70 to the control group. Patients in the abstinence group reduced their alcohol intake from 16.8±7.7 to 2.1±3.7 standard drinks per week (a reduction of 87.5%), and patients in the control group reduced their alcohol intake from 16.4±6.9 to 13.2±6.5 drinks per week (a reduction of 19.5%). After a 2-week blanking period, atrial fibrillation recurred in 37 of 70 patients (53%) in the abstinence group and in 51 of 70 patients (73%) in the control group. The abstinence group had a longer period before recurrence of atrial fibrillation than the control group (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; P = 0.005). The atrial fibrillation burden over 6 months of follow-up was significantly lower in the abstinence group than in the control group (median percentage of time in atrial fibrillation, 0.5% [interquartile range, 0.0 to 3.0] vs. 1.2% [interquartile range, 0.0 to 10.3]; P = 0.01).Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation. (Funded by the Government of Victoria Operational Infrastructure Support Program and others; Australian New Zealand Clinical Trials Registry number, ACTRN12616000256471.).