tbuckley/cabot-search huggingface dataset:
MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences
Authors: Alberto L′Abbate, Doron Tolomeo, Ingrid Cifola, Marco Severgnini, Antonella Turchiano, Bartolomeo Augello, Gabriella Squeo, Pietro D′Addabbo, Debora Traversa, Giulia Daniele, Angelo Lonoce, Mariella Pafundi, Massimo Carella, Orazio Palumbo, Anna Dolnik, Dominique Muehlematter, Jacqueline Schoumans, Nadine Van Roy, Gianluca De Bellis, Giovanni Martinelli, Giuseppe Merla, Lars Bullinger, Claudia Haferlach, Clelia Tiziana Storlazzi
Journal: Leukemia (2018)

Double minutes (dmin), homogeneously staining regions, and ring chromosomes are vehicles of gene amplification in cancer. The underlying mechanism leading to their formation as well as their structure and function in acute myeloid leukemia (AML) remain mysterious. We combined a range of high-resolution genomic methods to investigate the architecture and expression pattern of amplicons involving chromosome band 8q24 in 23 cases of AML (AML-amp). This revealed that different MYC-dmin architectures can coexist within the same leukemic cell population, indicating a step-wise evolution rather than a single event origin, such as through chromothripsis. This was supported also by the analysis of the chromothripsis criteria, that poorly matched the model in our samples. Furthermore, we found that dmin could evolve toward ring chromosomes stabilized by neocentromeres. Surprisingly, amplified genes (mainly PVT1) frequently participated in fusion transcripts lacking a corresponding DNA template. We also detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in AML-amp cases versus AML with a normal karyotype. Our results show that 8q24 amplicons in AML are surprisingly plastic DNA structures with an unexpected association to novel fusion transcripts and circular RNAs.
Endoscopic submucosal dissection of a squamous cell carcinoma of the esophagus developing in the area of a previous Heller’s myotomy for achalasia
Authors: Dario Biasutto, Jérôme Rivory, Sabine Roman, François Mion, Jean-Christophe Saurin, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2017)

Achalasia is considered a risk factor for esophageal cancer; nevertheless, there is no consensus for any regular screening [1] [2]. A few reports have described early esophageal cancer associated with achalasia that has been resected by endoscopy [3] [4]. Here we report a case of endoscopic submucosal dissection (ESD) for a squamous cell carcinoma that developed in the area of a previous Heller’s myotomy.
Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis
Authors: Alexej Knaus, Jean Tori Pantel, Manuela Pendziwiat, Nurulhuda Hajjir, Max Zhao, Tzung-Chien Hsieh, Max Schubach, Yaron Gurovich, Nicole Fleischer, Marten Jäger, Sebastian Köhler, Hiltrud Muhle, Christian Korff, Rikke S Møller, Allan Bayat, Patrick Calvas, Nicolas Chassaing, Hannah Warren, Steven Skinner, Raymond Louie, Christina Evers, Marc Bohn, Hans-Jürgen Christen, Myrthe van den Born, Ewa Obersztyn, Agnieszka Charzewska, Milda Endziniene, Fanny Kortüm, Natasha Brown, Peter N Robinson, Helenius J Schelhaas, Yvonne Weber, Ingo Helbig, Stefan Mundlos, Denise Horn, Peter M Krawitz
Journal: Genome Medicine (2018)

Glycosylphosphatidylinositol biosynthesis defects (GPIBDs) cause a group of phenotypically overlapping recessive syndromes with intellectual disability, for which pathogenic mutations have been described in 16 genes of the corresponding molecular pathway. An elevated serum activity of alkaline phosphatase (AP), a GPI-linked enzyme, has been used to assign GPIBDs to the phenotypic series of hyperphosphatasia with mental retardation syndrome (HPMRS) and to distinguish them from another subset of GPIBDs, termed multiple congenital anomalies hypotonia seizures syndrome (MCAHS). However, the increasing number of individuals with a GPIBD shows that hyperphosphatasia is a variable feature that is not ideal for a clinical classification.We studied the discriminatory power of multiple GPI-linked substrates that were assessed by flow cytometry in blood cells and fibroblasts of 39 and 14 individuals with a GPIBD, respectively. On the phenotypic level, we evaluated the frequency of occurrence of clinical symptoms and analyzed the performance of computer-assisted image analysis of the facial gestalt in 91 individuals.We found that certain malformations such as Morbus Hirschsprung and diaphragmatic defects are more likely to be associated with particular gene defects (PIGV, PGAP3, PIGN). However, especially at the severe end of the clinical spectrum of HPMRS, there is a high phenotypic overlap with MCAHS. Elevation of AP has also been documented in some of the individuals with MCAHS, namely those with PIGA mutations. Although the impairment of GPI-linked substrates is supposed to play the key role in the pathophysiology of GPIBDs, we could not observe gene-specific profiles for flow cytometric markers or a correlation between their cell surface levels and the severity of the phenotype. In contrast, it was facial recognition software that achieved the highest accuracy in predicting the disease-causing gene in a GPIBD.Due to the overlapping clinical spectrum of both HPMRS and MCAHS in the majority of affected individuals, the elevation of AP and the reduced surface levels of GPI-linked markers in both groups, a common classification as GPIBDs is recommended. The effectiveness of computer-assisted gestalt analysis for the correct gene inference in a GPIBD and probably beyond is remarkable and illustrates how the information contained in human faces is pivotal in the delineation of genetic entities.
Supportive care day hospital: A new tool for palliative care in cancer centers.
Authors: Carole Bouleuc
Journal: Journal of Clinical Oncology (2017)

170 Background: In May 2005, the Curie Institute in Paris opened the first supportive care day hospital in France. This type of new ward is now very frequent in the French comprehensive cancer centers. Methods: Patients are managed by the palliative care team with a two-part team of a physician and a nurse in order to address their supportive care needs: advanced-care symptoms, psychosocial distress, medical questions and concerns, support need in decision making, end of life care preference and advance care plan when patients or caregivers when needed. Depending of the needs identified by the palliative care team assess, at least 2 of the following healthcare professionals will intervene: oncologist, pain physician, psycho-oncologist, dietitician, social worker, physiotherapist. Coordination with the home care team takes systematically place (with general practitioner, nurse and home palliative care team). New symptoms occurrence are explored with biological test or radiographic examination when necessary. Medical procedures are sometimes performed like venous perfusion therapy, blood transfusions, or draining effusion after ultrasonic tracking. It is possible to offer the patient hypnosis, relaxation or sophrology consultation. Eventually at the end of the in-patient stay, the patient is given a medical synthesis with therapeutic recommendations and personalized care plan. 1 Physician and two nurses are needed to manage 4 patients every day. Results: In 2016 we have admitted 350 patients and performed 948 stays in our supportive rand 55% of them have breast cancer. Median survival since the first day at supportive care day hospital is 65 days. Death at home occurred in 15% of patients and in hospice for 62%. Home death is more often when patients don’t have any dyspnea are included in a home palliative care network and when they receive the last chemotherapy more than 30 days before death. More date will be shown. Conclusions: Supportive care day hospital is really a good tool for integrated palliative care, promoting collaboration with oncologists, coordination with home care teams, and advance care planning, so that patients can longer stay at home as they often hope so.
General practice warns of bankruptcy because of high service charges
Authors: Gareth Iacobucci
Journal: BMJ (2017)

A GP surgery serving 10 000 patients in Nottingham has said that it may be forced to close because of high service charges that are threatening to bankrupt its partners.

The Wellspring Surgery, which opened in 2012, is based at the £15m Valley Centre owned by Nottingham City Council. But the practice, which occupies part of the building, is leased by the government agency NHS Property Services (NHS PS).

The practice said that charges had increased 10-fold since 2012. This had made it impossible to replace a partner who had already left, unable to accept new patients, and put it on the verge of closure, it said.

The warning came as the …
Abstract 20041: Single Ventricle Outcome Following Neonatal Palliation of Severe Ebstein’s Anomaly With Modified Starnes Procedure
Authors: S. Ram Kumar, Nathan Noh, Novell Castillo, Brian Fagan, Grace Kung, Winfield J Wells, Vaughn A Starnes
Journal: Circulation (2015)

Background: We have previously shown that neonates in profound cardiogenic shock due to severe Ebstein’s anomaly can be successfully salvaged with fenestrated right ventricular (RV) exclusion and systemic to pulmonary shunt (modified Starnes procedure). The long-term outcome of single ventricle management in these patients is not known. Methods: We retrospectively reviewed the records of 26 patients who underwent neonatal Starnes procedure between 1989 and 2011. Patient demographics, clinical variables and outcome data were collected. Data is presented as mean ± standard errors or median (interquartile ranges). Results: 26 patients (12, 46% boys) underwent Starnes procedure at 7 (5-9) days of life. All were intubated and on prostacyclin infusion, 24 (92%) were inotrope-dependent and 23 (88%) had no antegrade flow from the RV. Two patients had had prior intervention (one tricuspid annuloplasty and one shunt alone). Three patients underwent non-fenestrated RV exclusion, two (67%) of whom died. Of the remaining 23, 3 (13%) died during the same hospitalization. The 21 neonatal survivors have been followed for 7 (6-8) years. One patient died after Glenn. The remaining 20 have successfully undergone Fontan completion with an indexed pulmonary resistance of 1.8 (1.2-2.3) W/m2 and mean pulmonary pressure of 12 (9-18) mm Hg. At last follow-up, all patients have normal left ventricular function, and all but one patient are in NYHA Class I symptoms. Two patients have required pacemaker implantation, while the rest are in sinus rhythm. Survival at 1, 5 and 10 years are 81±4%, 77±3% and 77±3%, respectively. Conclusion: Long-term single ventricle outcomes amongst neonatal survivors of modified Starnes procedure are excellent. There is reliable remodeling of the excluded RV and excellent function of the left ventricle.
Towards ‘off-the-shelf’ genetically modified T cells: prolonging functional engraftment in mice by CD8 veto T cells
Authors: N Or-Geva, R Gidron-Budovsky, L Radomir, Y Edelstein, A K Singh, R Sidlik-Muskatel, E Ophir, E Bachar-Lustig, Y Reisner
Journal: Leukemia (2017)
Studies on Starling's Law of the Heart
Authors: EUGENE BRAUNWALD, CHARLES J. FRAHM
Journal: Circulation (1961)

The hemodynamic functions of the left atrium were studied in 26 patients with disturbances of left ventricular function and in 16 subjects without any abnormalities of the cardiovascular system. Attention was directed to the effect of atrial systole on the relationship between mean left atrial pressure (MLAP) and left ventricular end-diastolic pressure (LVEDP). This relationship was considered to be a meaningful one in view of the importance of the LVEDP in determining the characteristics of ventricular contraction, and of the MLAP in determining the symptoms of left heart failure. In the subjects with normal cardiovascular systems, LVEDP-MLAP averaged 0.2 mm. Hg, but this value averaged 9.0 mm. Hg in patients with left ventricular disease, in whom left atrial contraction elevated LVEDP while permitting MLAP to remain at a significantly lower level. The magnitude of the pressure difference between LVEDP and MLAP was found to be dependent on the characteristics of atrial contraction; the height of the "a" wave appeared to be related to the atrial pressure prior to the onset of atrial contraction. The elevation of atrial pressure produced by atrial systole was found to vary directly with the time interval between the onset and the peak of the "a" wave and to vary inversely with the time interval between the peak of the "a" wave and the onset of ventricular contraction. Evidence was presented that in intact human subjects the characteristics of left atrial and left ventricular contraction are functions of the pressures in these chambers prior to the onset of their contraction, thus lending further support to the concept that Starling's law is operative in the human heart.
Infezione sporadica provocata da Escherichia coli O157 enteroemorragica
Authors: F Allerberger, L Beutin, T Cheasty, G Gonedera, H Karch
Journal: Eurosurveillance (1999)

Nel 1997, l'Austrian Federal Ministry of Health ha attivato un laboratorio di riferimento per l'Escherichia coli enteroemorragica presso il Laboratorio di Sanita Pubblica ad Innsbruck. Il laboratorio di riferimento conduce indagini sulle sorgenti di infezione per le intossicazioni alimentari allo scopo di prevenire ulteriori infezioni, collaborando, quando e il caso, con il progetto della Unione Europea (UE) 'Rete di Sorveglianza sul Controllo delle Malattie Infettive nella Comunita'. Qui di seguito e riportato un esempio specifico di questa cooperazione europea.
Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder
Authors: Judith Allardyce, Ganna Leonenko, Marian Hamshere, Antonio F. Pardiñas, Liz Forty, Sarah Knott, Katherine Gordon-Smith, David J. Porteous, Caroline Haywood, Arianna Di Florio, Lisa Jones, Andrew M. McIntosh, Michael J. Owen, Peter Holmans, James T. R. Walters, Nicholas Craddock, Ian Jones, Michael C. O’Donovan, Valentina Escott-Price
Journal: JAMA Psychiatry (2017)

Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes and mechanisms.
Clinical relevance of appraisals of persistent psychotic experiences in people with and without a need for care: an experimental study
Authors: Emmanuelle Peters, Thomas Ward, Mike Jackson, Peter Woodruff, Craig Morgan, Philip McGuire, Philippa A Garety
Journal: The Lancet Psychiatry (2017)

Cognitive models of psychosis propose that appraisals (ie, the interpretation and meaning attributed to experiences) are central to the transition from anomalous experiences to psychotic symptoms. In the Unusual Experiences Enquiry (UNIQUE) study, we investigated the role of appraisals by comparing individuals with persistent psychotic experiences without a need for care with patients and people without psychotic experiences.Eligible participants were patients with diagnosed psychotic disorders (clinical group) and adults in the general population with persistent psychotic experiences (non-clinical group) and without psychotic experiences (controls). The appraisals of psychotic experiences among people in the non-clinical and clinical groups were assessed by an in-depth interview, and appraisals of anomalous experiences induced by three experimental tasks were compared between all groups.We recruited 259 participants, 84 in the clinical group, 92 in the non-clinical group, and 83 controls. The clinical group was more likely than the non-clinical group to display paranoid, personalising interpretations of their psychotic experiences (p<0·008; p values are Sidak adjusted to account for multiple testing) and less likely to have normalising (p<0·008) and supernatural (p=0·039) explanations. The clinical group also appraised their psychotic experiences as being more negative, dangerous, and abnormal and less controllable than the non-clinical group (all p<0·005), but groups did not differ for attributions of general externality (p=0·44). For experimentally induced anomalous experiences, the clinical group endorsed more threatening appraisals on all tasks than the non-clinical group (p<0·003), who did not differ from the control group (p=0·07-0·6). The pattern was similar for ratings of salience, distress, personal relevance, global threat, and incorporation of the induced experiences into participants' own psychotic experiences.We provide robust evidence that the way psychotic experiences are appraised differs between individuals with and without a need for care, supporting cognitive models of psychosis. Specifically, the absence of paranoid and threatening appraisals might protect against persistent psychotic experiences becoming clinically relevant.UK Medical Research Council.
Targeting Interleukin-1β Protects from Aortic Aneurysms Induced by Disrupted Transforming Growth Factor β Signaling
Authors: Francesco Da Ros, Raimondo Carnevale, Giuseppe Cifelli, Dario Bizzotto, Manuel Casaburo, Marialuisa Perrotta, Lorenzo Carnevale, Iolanda Vinciguerra, Stefania Fardella, Roberta Iacobucci, Giorgio M. Bressan, Paola Braghetta, Giuseppe Lembo, Daniela Carnevale
Journal: Immunity (2017)
Treatment patterns and outcomes in patients with non-small cell lung cancer (NSCLC) receiving biosimilar filgrastim for prophylaxis of chemotherapy-induced/febrile neutropenia: Results from the MONITOR-GCSF study
Authors: M. Aapro, A. Krendyukov, N. Höbel, P. Gascón
Journal: Annals of Oncology (2017)
Abstract 14066: Methamphetamine Associated Heart Failure, a New Epidemic
Authors: Marin Nishimura, Janet Ma, Isac C Thomas, Sutton Fox, Avinash Toomu, Sean Mojaver, Derek Juang, Alan Maisel
Journal: Circulation (2017)

Introduction: Methamphetamine is one of the most commonly abused illegal substances in the United States. Heart failure due to Methamphetamine use (MethHF) is a poorly characterized disease entity ...
Who, what, where, when, and how? Advance care planning documentation practices and accessibility in the electronic health record.
Authors: Evan Justin Walker, Ryan Mcmahan, Deborah Barnes, Mary Katen, Daniela Lamas, Rebecca Sudore
Journal: Journal of Clinical Oncology (2017)

2 Background: Documenting patients’ advance care planning (ACP) wishes is essential to providing value aligned care, as is having this documentation readily accessible. Early ACP is increasingly being recognized as integral to oncologic care, however, little is known about current documentation practices. In this cross-sectional study, we describe ACP documentation practices and accessibility of documented ACP discussions in the electronic health record (EHR). Methods: Participants were recruited from outpatient clinics at the San Francisco VA, were ≥60 years old, with ≥2 chronic/serious conditions and ≥2 primary care visits in the past year. ACP documentation was abstracted from the EHR in 2013-2015 and included any prior legal forms/orders and ACP discussions documented within the prior five years. Frequency and type of ACP documentation was calculated using percentages and means. For discussions, author discipline and location of documentation was determined. Discussions were deemed “accessible” if documented in a designated ACP posting location or “not easily accessible” if recorded as free text in progress notes. Results: The mean age of 414 participants was 71 years (SD ± 8), 9% were women, 43% were non-white, and 51% had documented ACP including 149 (36%) with ACP forms and 138 (33%) with ACP discussions. Seventy-five (54%) discussions were documented by social workers and 49 (36%) by primary care providers. However, 76 (55%) discussions were not easily accessible. For 27 (18%) participants with advance directives, subsequent discussions documented a change in treatment preferences. Nineteen (70%) discussions reporting a change in wishes were not easily accessible. Conclusions: Half of chronically ill, older patients had documented ACP wishes, including a third with documented ACP discussions. Most discussions were documented by social workers and were not easily accessible, although discussions often represented changes from prior advance directives. Clinician education and EHR changes to ensure documented discussions are accessible are important patient-safety and quality improvement targets to ensure patients’ wishes are honored.
Perceptions of palliative care: Cancer and non-cancer.
Authors: Ingrid Harle, Christine Knott
Journal: Journal of Clinical Oncology (2017)

148 Background: Palliative Medicine consultation is greater for cancer than non-cancer patients. Decreased symptom burden, improved survival time and quality of life, and cost savings are associated with palliative care. Most patients do not receive information about palliative care until end of life, resulting in negative outcomes. We examined perceptions and access to Palliative Medicine for persons living with advanced illnesses. The purpose was to inform the design of palliative care pathways for cancer and non-cancer diagnoses. Methods: Using Interpretive Phenomenological Analysis, patients/caregivers with metastatic cancer, chronic kidney disease, chronic obstructive pulmonary disease and advanced heart failure were interviewed. This qualitative research method explores an individual’s lived illness experience. Interviews addressed care processes, teams, understanding of palliative care and goals of care. Six reviewers read, coded, categorized interview transcripts and extracted themes. Results: Fifty interviews were completed, 36/50 with metastatic cancer or COPD. Despite different diagnoses, themes were similar. Caregiver’s responses reflected the patient’s burden and overall experience. Themes were: focused individual care; multiple dimensions of time; 24/7 home care; physical and psychological impacts; and spirituality. Perceptions about Palliative Medicine remain aligned with end of life. Conclusions: Palliative Medicine remains associated with end of life, regardless of the diagnosis. Majority had limited access to palliative care, despite pursuing information on supportive services. They also expressed high expectations of receiving such information from physicians and other providers. Results are similar to national strategies on palliative care. The project’s findings have informed the design of clinical pathways for early integration of Palliative Medicine for patients with cancer and non-cancer diagnoses.
P1.03-066 Incorporation of a Molecular Prognostic Classifier Improves Conventional Non-Small Cell Lung Cancer TNM Staging
Authors: Johannes Kratz, Nancy Cook, Gavitt Woodard, Kirk Jones, Matthew Gubens, Thierry Jahan, Il-Jin Kim, Biao He, David Jablons, Michael Mann
Journal: Journal of Thoracic Oncology (2017)