tbuckley/cabot-search huggingface dataset:
Abstract B38: Developing a functional genomics platform to interrogate rare pediatric cancers
Authors: Andrew L. Hong, Glenn S. Cowley, Yuen-Yi Tseng, Jaime H. Cheah, Oliver Jonas, Mihir B. Doshi, Bryan D. Kynnap, Coyin Oh, Stephanie Meyer, Paul Clemons, Michael Burger, Francisca Vazquez, Barbara Weir, Gregory V. Kryukov, Alanna Church, Alma Imamovic, Aviad Tsherniak, Craig Bielski, Brian Crompton, Elizabeth Mullen, Charles Roberts, Carlos Rodriguez-Galindo, Katherine A. Janeway, Kimberly Stegmaier, Paul van Hummelen, Robert Langer, Levi A. Garraway, Stuart L. Schreiber, David E. Root, Jesse S. Boehm, William C. Hahn
Journal: Cancer Research (2016)

Abstract Of pediatric solid tumors, as many as 10% of tumors are categorized as rare. Many of these rare tumors lack standard effective known therapy. The ability to identify vulnerabilities for many rare tumors has been significantly limited by the lack of in vitro and in vivo models. Furthermore, current approaches to study such vulnerabilities are usually limited to a specific compound or target. Our objectives were 1) to develop a platform to collect tumor samples and generate in vitro models and 2) to develop systematic and orthogonal approaches focused on currently known druggable cancer targets to identify vulnerabilities in these difficult to treat cancers. We have developed a proof of concept cell line from a patient who succumbed to progressive undifferentiated sarcoma treated on an aggressive multi-therapy regimen. This cell line, in its early passages, has novel gene fusions that match that of the primary tumor. Furthermore, even at early passages, this cell line was amenable to high throughput functional screens. Using a targeted pooled shRNA screen (employing matched seed controls) and an analogous CRISPR screen we identified dependencies to XPO1 and CDK4. In parallel, compounds against these targets were identified in a small molecule compound screen. These targetable dependencies were further validated in vivo with a micro-dosing device. These observations identify new targets in this rare malignancy. Furthermore, this suggests that the interrogation of patient derived cell lines facilitates the identification of testable therapeutic approaches. Citation Format: Andrew L. Hong, Glenn S. Cowley, Yuen-Yi Tseng, Jaime H. Cheah, Oliver Jonas, Mihir B. Doshi, Bryan D. Kynnap, Coyin Oh, Stephanie Meyer, Paul Clemons, Michael Burger, Francisca Vazquez, Barbara Weir, Gregory V. Kryukov, Alanna Church, Alma Imamovic, Aviad Tsherniak, Craig Bielski, Brian Crompton, Elizabeth Mullen, Charles Roberts, Carlos Rodriguez-Galindo, Katherine A. Janeway, Kimberly Stegmaier, Paul van Hummelen, Robert Langer, Levi A. Garraway, Stuart L. Schreiber, David E. Root, Jesse S. Boehm, William C. Hahn. Developing a functional genomics platform to interrogate rare pediatric cancers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B38.
Clinical Observations on Five Patients with Uremic Pericardial Tamponade
Authors: Edward B. Hager
Journal: New England Journal of Medicine (1965)

PERICARDIAL inflammation is a relatively common complication of uremia. Although its occurrence seems superficially related to the degree of renal failure the pathogenesis is still obscure. The process may or may not produce pain, and pathologically is usually confined to an aseptic fibrinous inflammation, with a variable amount of exudate. It has been uncommon for tamponade to occur. Since uremic pericarditis is generally seen in the patients with the worst renal failure it is not surprising that death has usually intervened before secondary pericardial complications could become apparent.Now that dialysis and renal transplantation are becoming commonplace, changes in the . . .
Hodgkin's Disease with Monoclonal and Polyclonal Populations of Reed–Sternberg Cells
Authors: Michael Hummel, Katharina Ziemann, Hetty Lammert, Stefano Pileri, Elena Sabattini, Harald Stein
Journal: New England Journal of Medicine (1995)

There is strong evidence that Reed–Sternberg cells have a lymphoid phenotype, but clonally rearranged genes for B-cell and T-cell antigen receptors have not been demonstrable in tumor tissue from most patients with Hodgkin's disease. To elucidate this issue, we assayed single Reed–Sternberg cells from 12 patients with classic Hodgkin's disease of a B-cell immunophenotype to detect rearranged immunoglobulin variable-region heavy-chain (Vh) genes.
Preoperative Chemoradiotherapy and Postoperative Chemotherapy with Capecitabine +/- Oxaliplatin in Locally Advanced Rectal Cancer: Interim Analysis for Disease-Free Survival of Petacc 6
Authors: H.J. Schmoll, K. Haustermans, T.J. Price, B. Nordlinger, R. Hofheinz, J. Daisne, J.F. Janssens, B. Brenner, P. Schmidt, H.H. Reinel, S. Hollerbach, K. Caca, F.W.B. Fauth, C.V. Hannig, J. Zalcberg, N.C. Tebbutt, M. Mauer, C.G.M. Messina, M.P. Lutz, E. Van Cutsem
Journal: Annals of Oncology (2014)
Assaultive behavior among psychiatric outpatients
Authors: K Tardiff, H W Koenigsberg
Journal: American Journal of Psychiatry (1985)

Of 2,916 patients evaluated by psychiatric residents in the outpatient clinics of two large private psychiatric hospitals, 3% had manifested recent assaultive behavior toward other persons. In over half the cases the target of assault was a family member other than a child. Patients more likely to be assaultive were young and male and had a diagnosis of childhood or adolescent disorder or personality disorder. The authors compare these results with those from studies of assault among inpatients and recommend that physicians in outpatient as well as inpatient settings be familiar with the management of assaultive patients.
Iliofemoral Occlusive Disease Associated with Aneurysms of the Abdominal Aorta
Authors: Timothy S. Harrison, Jeremiah Turcotte, William J. Fry, Marion S. De Weese
Journal: New England Journal of Medicine (1964)

ANEURYSMECTOMY with prosthetic replacement of the removed arterial segment is now commonplace, and accepted as the treatment of choice for aneurysms of the abdominal aorta. We have been struck by the high frequency of associated iliofemoral occlusive problems in these patients and believe that this feature of their disease has not been sufficiently emphasized in the past. We also believe that obstructing arteriosclerotic lesions of the iliac and proximal femoral arteries should be dealt with at the time of aneurysmectomy, and we wish to present a review of our experience with these lesions in the past two years to . . .
P111 Respiratory Flow Limitation in the absence of Obstructive Sleep Apnoea responds to CPAP therapy
Authors: B Chakrabarti, S Emegbo, S Craig, J Heseltine, T Wright, N Duffy, JF O’Reilly
Journal: Thorax (2015)

<h3>Background</h3> The Apnoea–Hypopnoea index (AHI) is regarded as a gold standard diagnostic marker of Obstructive Sleep Apnoea Syndrome (OSAS). However, a number of patients present with excessive daytime sleepiness (EDS), yet exhibit a raised Respiratory Disturbance Index (RDI), comprising of flow limited breaths in the presence of a normal AHI (&lt;5 events/hr). We sought to evaluate the benefits of CPAP in this “Flow Limitation” cohort compared to a matched population of OSAS subjects. <h3>Results</h3> 27 subjects (Mean age 47 (SD 8) years; ESS 17(4); 48% male; BMI 35.60 (8.12)) presented to our Sleep Service with EDS and undertook a cardio-respiratory polysomnograph, demonstrating an RDI &gt;15 and AHI &lt;5 (Mean RDI 16 (4); AHI 3(2); ODI 5(3)) 25 subjects were subsequently treated with CPAP. At “6-week compliance” visits, 20 (80%) were deemed compliant with CPAP (mean nightly usage 6.03 (1.47) hrs; pre-CPAP ESS 18(3) falling to 9 (4) following CPAP. Within the Flow Limitation cohort, statistically significant associations were observed between CPAP compliance and Female gender (100 v 55%), higher BMI (36.61 v 31.56), higher pre-CPAP ESS (18 v13) and lower Pulse Transit Time PTT (300.90 v 316 ms). This “Flow Limitation” cohort was compared with an age/gender matched “OSAS “cohort (ESS 15(5); BMI 38.33 (7.80) AHI 58.16 (25.79) ODI 48 (23)). 26 OSAS subjects were treated with CPAP with 19 (70%) deemed compliant (nightly usage 5.25 (3.55) hrs; pre-CPAP ESS 16 (5) falling to 10(5) following CPAP. Whilst the mean PTT of the OSAS cohort was lower than the “Flow Limitation” cohort, this did not reach statistical significance (298.85(15.04) v 306.44 (18.36) ms; ANOVA; p = 0.1) yet the PTT Deceleration Index (DI), a surrogate of physiological arousal, was significantly higher in the OSAS cohort (59.05(29.33) v 36.32(23.69)/hour; ANOVA; p = 0.003). <h3>Conclusion</h3> “Sleepy” subjects exhibiting an elevated Flow Limitation Index in the presence of a normal AHI appear to demonstrate a response to CPAP therapy comparable to that observed in OSAS. Female gender and a higher BMI appear to predict compliance with therapy, whilst the utility of Pulse Transit Time in guiding decision making in “sleepy” subjects with a normal AHI merits further study.
CD146 + cells are essential for kidney vasculature development
Authors: Kimmo J. Halt, Heikki E. Pärssinen, Sanna M. Junttila, Ulla Saarela, Sunder Sims-Lucas, Peppi Koivunen, Johanna Myllyharju, Susan Quaggin, Ilya N. Skovorodkin, Seppo J. Vainio
Journal: Kidney International (2016)

The kidney vasculature is critical for renal function, but its developmental assembly mechanisms remain poorly understood and models for studying its assembly dynamics are limited. Here, we tested whether the embryonic kidney contains endothelial cells (ECs) that are heterogeneous with respect to VEGFR2/Flk1/KDR, CD31/PECAM, and CD146/MCAM markers. Tie1Cre;R26RYFP-based fate mapping with a time-lapse in embryonic kidney organ culture successfully depicted the dynamics of kidney vasculature development and the correlation of the process with the CD31+ EC network. Depletion of Tie1+ or CD31+ ECs from embryonic kidneys, with either Tie1Cre-induced diphtheria toxin susceptibility or cell surface marker–based sorting in a novel dissociation and reaggregation technology, illustrated substantial EC network regeneration. Depletion of the CD146+ cells abolished this EC regeneration. Fate mapping of green fluorescent protein (GFP)-marked CD146+/CD31- cells indicated that they became CD31+ cells, which took part in EC structures with CD31+ wild-type ECs. EC network development depends on VEGF signaling, and VEGF and erythropoietin are expressed in the embryonic kidney even in the absence of any external hypoxic stimulus. Thus, the ex vivo embryonic kidney culture models adopted here provided novel ways for targeting renal EC development and demonstrated that CD146+ cells are critical for kidney vasculature development.
Nuclear magnetic resonance study of obsessive-compulsive disorder
Authors: H J Garber, J V Ananth, L C Chiu, V J Griswold, W H Oldendorf
Journal: American Journal of Psychiatry (1989)

Magnetic resonance imaging (MRI) of the brains of 32 patients who met the DSM-III criteria for obsessive-compulsive disorder and of 14 normal subjects frequently revealed abnormalities, but none was specific to obsessive-compulsive disorder. Spin-lattice relaxation time (T1) for right frontal white matter was prolonged in the patients compared to the control subjects, and the patients had greater right-minus-left T1 differences for frontal white matter. Right-minus-left T1 differences in the orbital frontal cortex were strongly correlated with symptom severity in the unmedicated patients and in the patients with family histories of obsessive-compulsive disorder.
Abstract 2875: Effect of Timing of Bone Marrow Cell Delivery on Cell Viability and Cardiac Recovery Following Myocardial Infarction
Authors: Rutger-Jan Swijnenburg, Johannes A Govaert, William Stein, Koen van der Bogt, Jeremy I Pearl, Grant Hoyt, Hannes Vogel, Robert C Robbins, Joseph C Wu
Journal: Circulation (2008)

Background: Despite ongoing clinical trails, the optimal time for delivery of bone marrow mononuclear cells (BMC) following myocardial infarction (MI) is unclear. We compared the viability and effe...
Book: The Journal of Men's Health and Gender
Authors: Tom O'Dowd
Journal: BMJ (2005)

People are worried about men and their health. Inequalities in male health are staggering. Nine out of 10 prisoners are poorly educated young males from our urban blackspots. Half are on short term sentences of six months or so and many will return to prison.​prison.




Figure 1



Elsevier, Annual subscription €405/$454 (institutional), €94/$105 (personal) ISSN 1571 8913 www.elsevier.com/locate/jmhg BMJ readers can request a trial subscription at www.ismh.org/ismhformular/newsletter.htm

Rating: ★★★⋆




In the deprived urban areas of Europe you will see many young girls pushing buggies with young babies. They usually travel in groups and you seldom see a male with them. They don't know it yet but they are a young matriarchy entering a prison all of their own, which will keep them and their children in poverty for much of their lives. Their kids are at increased risk of many things such as cot deaths, injuries, hyperactivity, and poor school performance.

All too many of the children have little experience of a father in their lives. The boy-man may be no more than a sperm donor and the relationship may break down before the baby is born. Hence the young man never gets to experience fatherhood.

Better off men often speak about the big impact that seeing their child being born has on them. They describe the feeling of responsibility that is fatherhood, how it leads them to plan for the future, reduce personal risks, buy insurance, worry about schools, and look for promotion. Most fathers are a force for good in their children's lives. The impact of the father as a role model for sons and daughters has hardly been researched, which is part of the problem. To explore the role of fathers in a systematic way society has to deem it important enough to want to know the answer.

It is hardly surprising that young biological fathers who do not experience the responsibilities of fatherhood remain as immature lads, take risks, and get into enough trouble to end up in prison. It is often easy to find out about their addiction status, suicidal intent, and literacy levels, but not as easy to find out if they are fathers. And yet being a father brings with it responsibilities that have a steadying effect on the individual and the community that is good for health.

The Journal of Men's Health and Gender is attempting to advance the study of such issues. It is thoughtful but robust enough not to shy away from important subjects such as the emergence of women in healthcare leadership (including publishing), the absence of men in refugee camps, and gender differences in coronary heart disease. And there was only one article on erectile dysfunction in the three first issues, which must be a record for a publication on men's health.

There is scope for original research along gender lines in order to add to our understanding of how men and women cope differently with health and illness. There is certainly an opportunity for the Journal of Men's Health and Gender to become an authority in the area.
Abstract P2-05-03: Whole genome transcriptome analysis of sequential breast to brain metastasis uncovers new signalling pathways and druggable targets
Authors: D Varešlija, A Fagan, P Buckley, M Farrell, A Hill, L Young
Journal: Cancer Research (2016)

Abstract The occurrence of brain metastasis (BM) in breast cancer (BC) is currently on the rise across all molecular subtypes with 10-30% reported incidence. The need to uncover the mechanisms underlying this clinically devastating complication is apparent, and in the current study we sought to identify BC cell mediators of BM. In our cohort of metastatic patients (n=196) we found that BM developed in 13% of the cases. Despite the previous reports of negative ER status being a risk factor for BM, the ER+ve patients accounted for 42% of all diagnosed BM. To elucidate the gene alterations required for successful colonisation of the brain we undertook RNA sequencing (RNA-seq) of sequential breast to brain metastasis of known receptor status (n=7).This study presents the first whole transcriptome next-generation RNA-seq analysis of resected BM and their matching primary breast tumours. We identified 500 differentially expressed genes (DEGs) (&amp;lt; 0.05, fcThreshold &amp;gt;±1.5), accounting for those that were both upregulated and downregulated in BM compared to the primary. Analysis of protein-coding genes identified collective ER-specific metastatic pathways. Additionally, common functional pathways altered included ECM, cell adhesion and neuronal differentiation. Our analysis of the BM transcriptomic landscape and verification in cell line models that preferentially metastasise to the brain has unravelled a complex network of driver genes, cooperating with stromal derived factors, responsible for the organ-specific behaviour of the metastatic cells. Genes such as ANTRX1, THBS2, FAP, VCAN and TIMP2 were found to be part of the invasion and migration network that drives the extravasation of the BM cells. Furthermore, an EMT stemness signalling network driven by ANTRX1and WNT pathway driven RUNX was prominent in the cells acquiring the ability to migrate to the brain. Additional work is being carried out on uncovering the adaptations that re-activate the dormant brain metastatic cells and the contribution of the neuronal niche in the facilitating the colonisation by the MBC. This study highlights the requirement of unique gene sets for the invasion, migration and colonisation to the brain and that functional characterisation of the DEGs will enable the identification of novel molecular targets for prevention and treatment of breast cancer BM. Citation Format: Varešlija D, Fagan A, Buckley P, Farrell M, Hill A, Young L. Whole genome transcriptome analysis of sequential breast to brain metastasis uncovers new signalling pathways and druggable targets. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-03.
MPTH-02MOLECULAR CLASSIFICATION BASED ON IDH1/2 AND TERT PROMOTER WELL-DEFINES SUBGROUPS WITH DIFFERENT OUTCOME IN ADULT DIFFUSE GLIOMAS: A REPORT FROM GLIOMA MOLECULAR CLASSIFICATION CONSORTIUM
Authors: Hideyuki Arita, Kai Yamasaki, Yuko Matsushita, Taishi Nakamura, Mitsuaki Shirahata, Kaoru Tamura, Yuzo Terakawa, Junya Fukai, Akitake Mukasa, Hiroyoshi Suzuki, Makoto Shibuya, Yonehiro Kanemura, Toshiki Yoshimine, Nobuhito Saito, Motoo Nagane, Keisuke Ueki, Takashi Komori, Ryo Nishikawa, Yoshitaka Narita, Koichi Ichimura
Journal: Neuro-Oncology (2015)

ISN-Harrlem consensus guidelines proposed incorporation of molecular information into the diagnostic criteria of brain tumors. The current recommendation for diffuse glioma is to identify IDH mutations and subclassify them into either astrocytoma or oligodendroglioma using the 1p19q or ATRX status. However, a major challenge in this scheme is to stratify IDH-wt tumors. We analyzed a series of 759 adult diffuse gliomas consisted of 171 WHO grade II, 218 grade III and 370 grade IV tumors for the IDH1/2, 1p19q and TERT promoter status. The combined IDH/TERT classification divided the series into four groups with distinct histopathological profiles and outcome. The IDH/TERT co-mutated tumors (Group A, n = 154) mainly consisted of oligodendroglial tumors (78%) and mostly harbored 1p19q co-deletion (93%). The second group was composed of IDH-mutant/TERT-wt (Group B, n = 131) and enriched with astrocytomas (69%). The double-negative (IDH wt and TERT wt) group (Group C, n = 239) showed a mixed histology, GBM being the most common (62%), however all the other histologies were also present. Tumors with IDH-wt/TERT-mut (Group D, n = 235) were mostly GBM (80%) or AA(15%). Overall survival (OS) significantly differed across the four groups (A, Not reached; B, 79 months; C, 21 months; D, 16 months). WHO grade did not associate with OS in Group A, B and D, suggesting the homogenous nature of these groups respectively. On the contrary, lower grade tumors showed significantly longer survival than grade IV tumors (33 months vs. 17 months, p < 0.001) in Group C, suggesting that IDH-wt gliomas are biologically heterogeneous group. We showed that TERT promoter mutation is a useful diagnostic marker which can stratify both IDH-mutant and IDH-wt gliomas into prognostically distinct subgroups.
Case 9-2016
Authors: Kenneth Rosenfield, Brian B. Ghoshhajra, David M. Dudzinski, James R. Stone
Journal: New England Journal of Medicine (2016)

A 29-year-old man presented with severe dyspnea and chest pain on the right side. Computed tomographic angiography revealed a filling defect in the main and right pulmonary arteries that was consistent with pulmonary embolism. Diagnostic procedures were performed.
Oral Treatment of Subacute Bacterial Endocarditis with Phenoxymethyl Penicillin (Penicillin V)
Authors: Charles A. Santos-Buch, M. Glenn Koenig, David E. Rogers
Journal: New England Journal of Medicine (1957)

THE current treatment of subacute bacterial endocarditis requires the intramuscular administration of large amounts of penicillin. Although this route is generally well tolerated, pain and inflammation at local sites of injection can become a significant problem in the management of certain patients. Because of low and unpredictable serum levels attained after oral administration of penicillin G, effective oral therapy has not previously been available.Recent studies on phenoxymethyl penicillin (penicillin V) have suggested that this agent may represent a better means of oral administration. This compound is stable and relatively insoluble at pH ranges below 3.0. It is readily converted . . .