tbuckley/cabot-search huggingface dataset:
Depth of tumor implantation affects response to in situ vaccination in a syngeneic murine melanoma model
Authors: Peter M Carlson, Manasi Mohan, Matthew Rodriguez, Vladimir Subbotin, Claire X Sun, Ravi B Patel, Jen Birstler, Jacquelyn A Hank, Alexander L Rakhmilevich, Zachary S Morris, Amy K Erbe, Paul M Sondel
Journal: Journal for ImmunoTherapy of Cancer (2021)

An important component of research using animal models is ensuring rigor and reproducibility. This study was prompted after two experimenters performing virtually identical studies obtained different results when syngeneic B78 murine melanoma cells were implanted into the skin overlying the flank and treated with an in situ vaccine (ISV) immunotherapy. Although both experimenters thought they were using identical technique, we determined that one was implanting the tumors intradermally (ID) and the other was implanting them subcutaneously (SC). Though the baseline in vivo immunogenicity of tumors can depend on depth of their implantation, the response to immunotherapy as a function of tumor depth, particularly in immunologically ‘cold’ tumors, has not been well studied. The goal of this study was to evaluate the difference in growth kinetics and response to immunotherapy between identically sized melanoma tumors following ID versus SC implantation. We injected C57BL/6 mice with syngeneic B78 melanoma cells either ID or SC in the flank. When tumors reached 190–230 mm 3 , they were grouped into a ‘wave’ and treated with our previously published ISV regimen (12 Gy local external beam radiation and intratumoral hu14.18-IL2 immunocytokine). Physical examination demonstrated that ID-implanted tumors were mobile on palpation, while SC-implanted tumors became fixed to the underlying fascia. Histologic examination identified a critical fascial layer, the panniculus carnosus, which separated ID and SC tumors. SC tumors reached the target tumor volume significantly faster compared with ID tumors. Most ID tumors exhibited either partial or complete response to this immunotherapy, whereas most SC tumors did not. Further, the ‘mobile’ or ‘fixed’ phenotype of tumors predicted response to therapy, regardless of intended implantation depth. These findings were then extended to additional immunotherapy regimens in four separate tumor models. These data indicate that the physical ‘fixed’ versus ‘mobile’ characterization of the tumors may be one simple method of ensuring homogeneity among implanted tumors prior to initiation of treatment. Overall, this short report demonstrates that small differences in depth of tumor implantation can translate to differences in response to immunotherapy, and proposes a simple physical examination technique to ensure consistent tumor depth when conducting implantable tumor immunotherapy experiments.
Radiologist who secretly filmed women in toilets on mobile phone is struck off
Authors: Clare Dyer
Journal: BMJ (2021)

A consultant radiologist who was twice convicted of voyeurism after hiding his mobile phone to film women in toilets has been struck off the UK medical register.

Mark McClure, 52, was only recently freed from prison after serving four and a half months of a nine month sentence imposed last December. His earlier conviction, in February 2017, was for installing his phone in a toilet air vent, although suspicious staff at Hillsborough Private Clinic in Northern Ireland, where he worked, spotted the ploy and no one was actually recorded. He received a nine month …
Advances in immunotherapy for hepatocellular carcinoma
Authors: Bruno Sangro, Pablo Sarobe, Sandra Hervás-Stubbs, Ignacio Melero
Journal: Nature Reviews Gastroenterology & Hepatology (2021)

Hepatocellular carcinoma (HCC) is a prevalent disease with a progression that is modulated by the immune system. Systemic therapy is used in the advanced stage and until 2017 consisted only of antiangiogenic tyrosine kinase inhibitors (TKIs). Immunotherapy with checkpoint inhibitors has shown strong anti-tumour activity in a subset of patients and the combination of the anti-PDL1 antibody atezolizumab and the VEGF-neutralizing antibody bevacizumab has or will soon become the standard of care as a first-line therapy for HCC, whereas the anti-PD1 agents nivolumab and pembrolizumab are used after TKIs in several regions. Other immune strategies such as adoptive T-cell transfer, vaccination or virotherapy have not yet demonstrated consistent clinical activity. Major unmet challenges in HCC checkpoint immunotherapy are the discovery and validation of predictive biomarkers, advancing treatment to earlier stages of the disease, applying the treatment to patients with liver dysfunction and the discovery of more effective combinatorial or sequential approaches. Combinations with other systemic or local treatments are perceived as the most promising opportunities in HCC and some are already under evaluation in large-scale clinical trials. This Review provides up-to-date information on the best use of currently available immunotherapies in HCC and the therapeutic strategies under development. Immunotherapeutic interventions might be effective tools for the treatment of hepatocellular carcinoma. This Review provides up-to-date information on the clinical use of currently available immunotherapies in hepatocellular carcinoma, the mechanisms of response and resistance, and the therapeutic strategies under development.
Preclinical evaluation for engraftment of CD34+ cells gene-edited at the sickle cell disease locus in xenograft mouse and non-human primate models
Authors: Naoya Uchida, Linhong Li, Tina Nassehi, Claire M. Drysdale, Morgan Yapundich, Jackson Gamer, Juan J. Haro-Mora, Selami Demirci, Alexis Leonard, Aylin C. Bonifacino, Allen E. Krouse, N. Seth Linde, Cornell Allen, Madhusudan V. Peshwa, Suk See De Ravin, Robert E. Donahue, Harry L. Malech, John F. Tisdale
Journal: Cell Reports Medicine (2021)

Sickle cell disease (SCD) is caused by a 20A > T mutation in the β-globin gene. Genome-editing technologies have the potential to correct the SCD mutation in hematopoietic stem cells (HSCs), producing adult hemoglobin while simultaneously eliminating sickle hemoglobin. Here, we developed high-efficiency viral vector-free non-footprint gene correction in SCD CD34+ cells with electroporation to deliver SCD mutation-targeting guide RNA, Cas9 endonuclease, and 100-mer single-strand donor DNA encoding intact β-globin sequence, achieving therapeutic-level gene correction at DNA (∼30%) and protein (∼80%) levels. Gene-edited SCD CD34+ cells contributed corrected cells 6 months post-xenograft mouse transplant without off-target δ-globin editing. We then developed a rhesus β-to-βs-globin gene conversion strategy to model HSC-targeted genome editing for SCD and demonstrate the engraftment of gene-edited CD34+ cells 10–12 months post-transplant in rhesus macaques. In summary, gene-corrected CD34+ HSCs are engraftable in xenograft mice and non-human primates. These findings are helpful in designing HSC-targeted gene correction trials.
Risk stratification of cardiac sequelae detected using cardiac magnetic resonance in late convalescence at the six-month follow-up of recovered COVID-19 patients
Authors: Hang Fu, Na Zhang, Yongli Zheng, Nan Jiang, Huayan Xu, Rong Xu, Linjun Xie, Zhongqin Zhou, Bin Kang, Tao Li, Jun Lin, Bennan Zhao, Tao Zeng, Keke Hou, Xiaoyu Niu, Yingkun Guo
Journal: Journal of Infection (2021)
Moving Beyond Medications That Act at the μ Receptor in the Treatment of Opioid Use Disorder
Authors: Eric C. Strain, Kyle M. Kampman, Roger D. Weiss
Journal: JAMA Psychiatry (2021)

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 Psychiatry 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 Psychiatry journal
E-selectin stimulates tyrosine kinase-dependent adhesiveness of 2 Estegrins in PMN: Role of an unidentified receptor
Authors: Licia Totani, Antonio Piccoli, Nicola Martelli, Stefano Manarini, Dietmar Vestweber, Giovanni De Gaetano, Chiara Cerletti, Virgilio Evangelista
Journal: Blood (2000)
Cancer drivers and clonal dynamics in acute lymphoblastic leukaemia subtypes
Authors: James B. Studd, Alex J. Cornish, Phuc H. Hoang, Philip Law, Ben Kinnersley, Richard Houlston
Journal: Blood Cancer Journal (2021)

To obtain a comprehensive picture of composite genetic driver events and clonal dynamics in subtypes of paediatric acute lymphoblastic leukaemia (ALL) we analysed tumour-normal whole genome sequencing and expression data from 361 newly diagnosed patients. We report the identification of both structural drivers, as well as recurrent non-coding variation in promoters. Additionally we found the transcriptional profile of histone gene cluster 1 and CTCF altered tumours shared hallmarks of hyperdiploid ALL suggesting a 'hyperdiploid like' subtype. ALL subtypes are driven by distinct mutational processes with AID mutagenesis being confined to ETV6-RUNX1 tumours. Subclonality is a ubiquitous feature of ALL, consistent with Darwinian evolution driving selection and expansion of tumours. Driver mutations in B-cell developmental genes (IKZF1, PAX5, ZEB2) tend to be clonal and RAS/RTK mutations subclonal. In addition to identifying new avenues for therapeutic exploitation, this analysis highlights that targeted therapies should take into account composite mutational profile and clonality.
Abstract 15744: Contemporary Rhythm Monitor Utilization Following Acute Ischemic Stroke
Authors: Xinye Li, Shaan Khurshid, Jeffrey M Ashburner, Steven J Atlas, Daniel E Singer, Ana T Lipsanopoulos, Priscilla R Lee, Aimee K Lin, Patrick T Ellinor, Emelia J Benjamin, Lee H Schwamm, Christopher D ANDERSON, Ludovic Trinquart, Steven A Lubitz
Journal: Circulation (2020)

Introduction: Post-stroke rhythm monitoring can detect occult AF, but contemporary utilization is not well-understood. We sought to quantify monitor deployment in a real-world stroke population and assess whether it is calibrated to clinical AF risk. Methods: We performed a single-center analysis of consecutive patients with acute ischemic stroke 10/2018-6/2019 and no AF history and assessed monitor utilization (Holter/ECG, event/patch, and implantable loop recorder [ILR]) at 6 months. We evaluated predictors of monitor deployment using Cox proportional hazards modeling with the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) AF risk score, stroke subtype, and discharge disposition. We estimated the cumulative incidence of monitoring both overall and in stroke subtype and discharge disposition subgroups, accounting for the competing risk of death and with adjustment for other factors using inverse probability weighting. Results: Of 532 acute stroke patients (mean age 65, 47% female), the 6-month incidence of monitoring was 36.2% (95% CI 31.5-40.9, Figure ). Monitoring included Holter/event monitor (74.3%), ILR (21.2%) or both (4.5%). Monitoring was more likely after cryptogenic (hazard ratio 4.36, 95%CI 3.12-6.1; 6-month monitor incidence 69.3%) and cardioembolic (1.80, 1.00-3.22; 37.3%) stroke, as opposed to other/unknown subtype (24.3%). Monitoring was also more likely after discharge home (1.92, 1.39-2.66; 47.6%) versus facility (27.7%). Monitoring was not associated with AF risk (1.08, 0.93-1.27, per 1 SD increase in CHARGE-AF), even though AF risk was associated with AF (1.67, 1.3-2.15, per 1 SD increase in CHARGE-AF). Conclusions: Rhythm monitors are underutilized after stroke. Interventions to encourage monitor deployment according to AF risk may improve the efficiency of post-stroke monitoring. Figure. Cumulative incidence of monitoring overall and within strata of stroke subtype and discharge disposition
Abstract 17326: The Effect of Maintenance of Antegrade Pulmonary Blood Flow Upon Bidirectional Glenn on Pre- and Post-Fontan Outcomes
Authors: Jae Suk Baek, Chun Soo Park, Eun Seok Choi, Bo Sang Kwon, Tae-Jin Yun, Jeong Jin Yu, Young-Hwue Kim, Jae-kon Ko
Journal: Circulation (2018)

Introduction: Maintaining pulsatility at the time of bidirectional Glenn (BDG) has theoretical advantages and disadvantages. The practice is diverse throughout the centers and individual surgeons without clear rationale behind its application. We sought to investigate the impact of antegrade pulmonary blood flow on pre- and post-Fontan outcomes. Methods: From 2003 through June 2014, among 237 patients who underwent BDG as an interim palliation for functional single ventricle (FSV), patients with preexisting pulmonary blood flow from the ventricle before BDG were included and patients undergoing Kawashima operation or having history of Norwood operation or bilateral pulmonary arterial band were excluded (n=151). Patients were grouped by their presence or absence of antegrade pulmonary blood flow following BDG: group 1 (pulsatile) (n=73) or group 2 (non-pulsatile) (n=78). The pre- and post-Fontan outcomes were compared between two groups. Results: Age and weight at BDG were 7 months and 7.8kg. Oxygen saturation was higher in group 1 (84±4%) compared to group 2 (82±4%) before Fontan (p&lt;0.001). The level of brain natriuretic peptide (BNP) was similar before Fontan (p=0.966). In pre-Fontan cardiac catheterization, mean pulmonary arterial pressure was similar (Group 1: 11±4mmHg vs. Group 2: 10±4mmHg, p=0.146), McGoon ratio seemed higher in group 1(2.6±0.6) compared to group 2(2.3±0.4) (p=0.057), and pulmonary vascular resistance was lower in group 1(1.3±0.7) compared to group 2(1.6±0.7)(p=0.038). A total of 136 patients (90%) underwent Fontan operation. Duration of stay in the intensive care unit (p=0.766), stay in hospital (p=0.142), and indwelling chest tube (p=0.128) was not different between groups. Overall survival after BDG was better in group 2 (p=0.046) [Figure]. In multivariable analysis, maintenance of pulsatility was identified as a risk factor for survival after BDG (p=0.012, HR 4.1 [CI 1.4-12.4]). Conclusions: Maintaining pulsatility at the time of BDG in FSV might be beneficial for pulmonary arterial growth and oxygen saturation without increasing BNP. However, such beneficial effect did not have a positive effect on subsequent Fontan outcome. Attention must be paid to the negative effect of pulsatility on overall post-BDG survival.
SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study
Authors: Andrew G Letizia, Yongchao Ge, Sindhu Vangeti, Carl Goforth, Dawn L Weir, Natalia A Kuzmina, Corey A Balinsky, Hua Wei Chen, Dan Ewing, Alessandra Soares-Schanoski, Mary-Catherine George, William D Graham, Franca Jones, Preeti Bharaj, Rhonda A Lizewski, Stephen E Lizewski, Jan Marayag, Nada Marjanovic, Clare M Miller, Sagie Mofsowitz, Venugopalan D Nair, Edgar Nunez, Danielle M Parent, Chad K Porter, Ernesto Santa Ana, Megan Schilling, Daniel Stadlbauer, Victor A Sugiharto, Michael Termini, Peifang Sun, Russell P Tracy, Florian Krammer, Alexander Bukreyev, Irene Ramos, Stuart C Sealfon
Journal: The Lancet Respiratory Medicine (2021)
Geriatric emergencies: psychiatric or medical?
Authors: E L Bassuk, S Minden, R Apsler
Journal: American Journal of Psychiatry (1983)

To determine how the elderly use the emergency room, the authors compared emergency patients 65 years old and older with younger patients in terms of demographics, clinical factors, patterns of emergency room use, and clinicians' responses. They found that, like younger patients, the elderly had scanty social supports but, unlike younger patients, came for care repeatedly with somatic complaints. Despite coexisting medical and psychiatric illnesses, these patients were generally managed by one service without consultation from the other. The authors, who found no differences in physicians' attitudes toward younger and older patients, emphasize the need for a holistic, psychobiologic approach to the care of the elderly emergency patient.
Cognitive and Adaptive Functioning in Youth With Retinoblastoma: A Longitudinal Investigation Through 10 Years of Age
Authors: Victoria W. Willard, Ibrahim Qaddoumi, Haitao Pan, Chia-Wei Hsu, Rachel C. Brennan, Matthew W. Wilson, Carlos Rodriguez-Galindo, Kristin Goode, Kendra Parris, Sean Phipps
Journal: Journal of Clinical Oncology (2021)

PURPOSE To describe the trajectory of cognitive and adaptive functioning in pediatric patients with retinoblastoma from diagnosis through age 10. This is an extension of a previous report that discussed findings from diagnosis through age 5. PATIENTS AND METHODS Ninety-eight participants with retinoblastoma completed psychological assessments as part of their enrollment on an institutional treatment protocol, with 73 completing an additional assessment at age 10. Trajectories of adaptive and cognitive functioning were determined, with data analyzed by treatment strata, and patients with 13q- analyzed separately. RESULTS Longitudinal trajectories identified a significant change point in trends at age 5, with functioning declining from diagnosis through age 5 and then increasing from age 5 to age 10. This pattern was observed for all strata for adaptive functioning, but only for enucleation-only patients (strata C low) for cognitive functioning. Cognitive trajectories were also influenced by laterality and enucleation status. At age 10, overall functioning was generally within the average range, although estimated intelligence quotient was significantly below the normative mean for enucleation-only (C low) patients. Patients with 13q- demonstrated very low functioning, but few analyses were significant because of small sample size. CONCLUSION The results generally indicate that previously demonstrated declines in functioning from diagnosis through age 5 improve by age 10. However, these early declines, as well as the continuous difficulties observed in patients treated with enucleation only, suggest the need for early intervention services for young patients with retinoblastoma. Continuous monitoring of the psychological functioning of patients with retinoblastoma, increased awareness of risk factors such as unilateral disease, enucleation, race, and surgery-only treatment plans, and referral to Early Intervention for all patients are indicated.
Intraoperative radiation therapy (IORT)for1200 early breast tumors
Authors: M. Epstein, M. Silverstein, P. Chen, K. Lin, B. Kim, S. Khan, L. Snyder, L. E. Guerra, C. Coleman
Journal: Cancer Research (2021)

Introduction: Two prospective randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiationtherapy (IORT) to be a safe alternative with a low-risk of local recurrence compared to whole breast radiationtherapy following breast conserving surgery for selected low-risk patients  We report the first 1200 tumors treatedwith this modality at our facility  Methods: 1200 distinct breast cancers in 1169 patients (31 bilateral) were treatedwith breast conserving surgery and X-ray IORT, using the Xoft Accent System from June 2010 to November 2018 Patients were enrolled in an IORT registry trial and data were collected at 1 week, 1 month, 6 months, 1 year, andyearly thereafter  The primary endpoint was local recurrence  Results: To date, there have been 61 events in 54patients: 50 ipsilateral local recurrences (14 DCIS and 36 invasive), 7 regional nodal recurrences and 4 distantrecurrences  Of local recurrences, 9 were within the IORT field, 21 outside of the IORT field but within the samequadrant as the index cancer, and 20 were new cancers in different quadrants  There has been no breast cancerrelated deaths and 27 non-breast cancer deaths  Currently, with a median follow-up of 52 months, Kaplan Meieranalysis projects 5 2 % local recurrence rate at 5 years  In the table below, the five-year probability of localrecurrence is analyzed by quadrant and/or type of recurrence (all recurrences or just invasive)  Using the 2017,ASTRO Categories, 520 patients (43%) were suitable for IORT, 415 (35%) were cautionary, and 265 (22%) wereunsuitable for IORT after final histopathology was evaluated  Conclusion: IORT is profoundly convenient  Whenused as the only adjuvant breast irradiation, it eliminates approximately 15-35 outpatient visits  This has become increasingly important during the current COVID-19 pandemic  In the group of patients described here, more that100,000 patient-hours were saved  The local, regional, and distant recurrence rates observed in this trial wereslightly higher than those of the prospective randomized TARGIT-A and ELIOT Trials  This may be explained by22% of our patients being considered unsuitable for IORT by ASTRO Criteria  The low complication rates previouslyreported by our group as well as the low recurrence rates reported in this study support the cautious use andcontinued study of X-ray IORT in women with low-risk breast cancer
Metabolome and lipidome derangements during a severe mast cell activation event in a patient with indolent systemic mastocytosis
Authors: Thomas Boehm, Robin Ristl, Saijo Joseph, Karin Petroczi, Kristaps Klavins, Peter Valent, Bernd Jilma
Journal: Journal of Allergy and Clinical Immunology (2021)

The number of mast cells in various organs is elevated manifold in individuals with systemic mastocytosis. Degranulation can lead to life-threatening symptomatology. No data about the alterations of the metabolome and lipidome during an attack have been published.Our aim was to analyze changes in metabolomics and lipidomics during the acute phase of a severe mast cell activation event.A total of 43 metabolites and 11 lipid classes comprising 200 subvariants from multiple plasma samples in duplicate, covering 72 hours of a severe mast cell activation attack with nausea and vomiting, were compared with 2 baseline samples by using quantitative liquid chromatography-mass spectrometry.A strong enterocyte dysfunction reflected in an almost 20-fold reduction in the functional small bowel length was extrapolated from strongly reduced ornithine and citrulline concentrations and was very likely secondary to severe endothelial cell dysfunction with hypoperfusion and extensive vascular leakage. Highly increased histamine and lactate concentrations accompanied the peak in clinical symptoms. Elevated asymmetric and symmetric dimethylarginine levels combined with reduced arginine levels compromised endothelial nitric oxide synthase activity and nitric oxide signaling. Specific and extensive depletion of many lysophosphatidylcholine variants indicates localized autotaxin activation and lysophosphatidic acid release. A strong correlation of clinical parameters with histamine concentrations and symptom reduction after 100-fold elevated plasma diamine oxidase concentrations implies that histamine is the key driver of the acute phase.Rapid elimination of elevated histamine concentrations through use of recombinant human diamine oxidase, supplementation of lysophosphatidylcholine for immunomodulation, inhibition of autotaxin activity, and/or blockade of lysophosphatidic acid receptors might represent new treatment options for life-threatening mast cell activation events.