tbuckley/cabot-search huggingface dataset:
Genome-Wide Significant Loci: How Important Are They?
Authors: Johan L.M. Björkegren, Jason C. Kovacic, Joel T. Dudley, Eric E. Schadt
Journal: Journal of the American College of Cardiology (2015)

Genome-wide association studies (GWAS) have been extensively used to study common complex diseases such as coronary artery disease (CAD), revealing 153 suggestive CAD loci, of which at least 46 have been validated as having genome-wide significance. However, these loci collectively explain <10% of the genetic variance in CAD. Thus, we must address the key question of what factors constitute the remaining 90% of CAD heritability. We review possible limitations of GWAS, and contextually consider some candidate CAD loci identified by this method. Looking ahead, we propose systems genetics as a complementary approach to unlocking the CAD heritability and etiology. Systems genetics builds network models of relevant molecular processes by combining genetic and genomic datasets to ultimately identify key "drivers" of disease. By leveraging systems-based genetic approaches, we can help reveal the full genetic basis of common complex disorders, enabling novel diagnostic and therapeutic opportunities.
Optimal length for tongue protrusion force in humans
Authors: Julian Saboisky, Billy Luu, Jane Butler, Simon Gandevia
Journal: European Respiratory Journal (2013)

Purpose There have been relatively few investigations of the length–tension curves for tongue protrusion (e.g. 1). Resting (not optimal) length is usually used with the tongue tip near the incisors to measure peak tongue protrusion force (e.g. 2). As the human tongue is a unique structure with intrinsic and extrinsic muscles in a hydrostat, its force generating capacity in protrusion likely reflects the interaction of several muscles.  Methods Quasi–isometric maximum voluntary contractions of tongue protrusion were measured in 10 healthy subjects (n=10; 6F; 27.5±1.1 years). Tongue force was recorded with the tongue tip at 8 different positions relative to the incisors, at 12 and 4mm protrusion, 0 position, and 4, 12, 16, 24 and 32mm retraction. Measurements were made at FRC. Results from each subject were normalised to the maximal value. Results given as Mean±SEM.  Results Mean peak force displayed a typical length–tension curve over the range of positions, increasing from 24±2N, at 32mm retraction, to a peak of 28±3N, at 24mm retraction. When the tongue was protruded by 12mm, mean peak force was 15±2N. Subjects generated greater forces when the tongue was retracted than when protruded (p  Conclusion These results describe voluntary protrusion forces across a wide range of tongue positions. Further studies are needed to assess the physiological relevance of these findings.  1. BuSha, et al. Resp Physiol Neurobiol (2002).  2. Eckert, et al. J Appl Physiol (2011).
The evolution of the mitochondrial D-loop region and the origin of modern man.
Authors: G Pesole, E Sbisá, G Preparata, C Saccone
Journal: Molecular Biology and Evolution (1992)

The origin of modern man is a highly debated issue that has recently been tackled by using mitochondrial DNA sequences. The limited genetic variability of human mtDNA has been explained in terms of a recent common genetic ancestry, thus implying that all modern-population mtDNAs originated from a single woman who lived in Africa less than 0.2 Mya. This divergence time is based on both the estimation of the rate of mtDNA change and its calibration date. Because different estimates of the rate of mtDNA evolution can completely change the scenario of the origin of modern man, we have reanalyzed the available mitochondrial sequence data by using an improved version of the statistical model, the "Markov clock," devised in our laboratory. Our analysis supports the African origin of modern man, but we found that the ancestral female from which all extant human mtDNAs originated lived in a time span of 0.3-0.8 Mya. Pushing back the date of the deepest root of the human implies that the earliest divergence would have been in the Homo erectus population.
Early Neutropenia is Associated with Survival in Men with Metastatic Castration-Resistant Prostate Cancer (Mcrpc) When Treated with Cabazitaxel: an Analysis of Tropic Phase III Trial
Authors: A. Meisel, S. von Felten, J.S. de Bono, R. De Wit, O. Sartor, F. Stenner-Liewen
Journal: Annals of Oncology (2014)
Basal cell carcinoma: cell of origin, cancer stem cell hypothesis and stem cell markers
Authors: K. Sellheyer
Journal: British Journal of Dermatology (2010)

Cancer stem cells have recently been described in several high-grade neoplasms. It is still unclear if they also occur in cutaneous malignancies. Cancer stem cells are not identical with somatic stem cells. The presence of tumour stem cells in a neoplasm does not in itself equal that the tumour derives from a somatic stem cell. A cell originally lacking stem cell characteristics could also acquire those features during the course of carcinogenesis and then becomes the clonal founder cell of a tumour. Basal cell carcinoma (BCC) is the most common cutaneous malignancy. A plethora of various stem cell markers has been applied to study its cellular origin. Intriguingly, the anatomical origin of BCC is still uncertain. This review will discuss the various stem cell markers used in BCC and the cellular origin of this tumour, and touches briefly on the possibility of cancer stem cells in BCC. If BCC or other skin cancers harbour tumour stem cells, these cells could be specifically targeted, making use of specific cell surface molecules such as receptor proteins. Novel drugs directed against those receptor proteins could replace currently available shotgun approaches including imiquimod.
The Enduring Search for the Koplik Spots of Psychosis
Authors: Paolo Fusar-Poli
Journal: JAMA Psychiatry (2015)

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
Regulated Necrotic Cell Death
Authors: Jason Karch, Jeffery D. Molkentin
Journal: Circulation Research (2015)

Although the molecular effectors of apoptotic cell death have been largely annotated over the past 30 years, leading to a strong biological understanding of this process and its importance in cell biology, cell death through necrosis has only recently been accepted as a similarly regulated process with definable molecular effectors. The mitochondria are important and central mediators of both apoptosis and regulated necrosis. In apoptosis, the B-cell leukemia/lymphoma 2 (Bcl-2) family members Bcl-2-associated protein x (Bax) and Bcl-2 homologues antagonist/killer (Bak) undergo oligomerization in the outer mitochondrial membrane resulting in the release of apoptosis inducing substrates and the activation of caspases and nucleases. In contrast, during necrosis the mitochondria become dysfunctional and maladaptive in conjunction with reactive oxygen species production and the loss of ATP production, in part through opening of the mitochondrial permeability transition pore. Although regulated necrosis is caspase-independent, recent evidence has shown that it still requires the apoptotic regulators Bax/Bak, which can regulate the permeability characteristics of the outer mitochondrial membrane in their nonoligomerized state. Here, we review the nonapoptotic side of Bcl-2 family, specifically the role of Bax/Bak in regulated necrotic cell death. We will also discuss how these Bcl-2 family member effectors could be part of a larger integrated network that ultimately decides the fate of a given cell somewhere within a molecular continuum between apoptosis and regulated necrosis.
Genetics and pulmonary medicine bullet 5: Genetics of drug resistant tuberculosis
Authors: A Telenti
Journal: Thorax (1998)

The emergence of multidrug-resistant tuberculosis (MDR-TB), generally defined as resistance to at least isoniazid and rifampicin, has generated concern for the future of tuberculosis control.1 The global magnitude of the problem is not well known. Most of the available studies are non-representative surveys of a population or a country, frequently failing to discriminate between primary and acquired resistance. However, emerging data (fig 1) suggest that, while multidrug resistance may not be a widespread problem, it remains a public health threat in areas with a high prevalence of tuberculosis and suboptimal tuberculosis control programmes.2 Progress in understanding of the basis of drug action and resistance is the key to development of diagnostic strategies, novel drugs and treatment programmes, and to gaining insight into the pathogenicity of drug resistant strains.



Figure 1 
Global rates of drug-resistant tuberculosis. Median, upper and lower range values reported in various studies are shown. For each drug primary (P) and acquired (A) resistance values are presented separately. WHO-IUATLD Global Surveillance Program 1985–1994.1 



Bacteria use a number of strategies to achieve drug resistance. These can be roughly summarised into three categories: (1) barrier mechanisms (decreased permeability and efflux pumps); (2) degrading or inactivating enzymes—for example, β-lactamases; and (3) drug target modifications—for example, single mutation in a key gene. The genetic information for such properties may be acquired via exogenous mobile genetic elements such as plasmids or transposons, or it may reside in the chromosome.

Mycobacteria are not basically different from many other bacteria in that they use several of these strategies. Firstly, mycobacteria are characterised by a specialised cell wall which displays significantly reduced permeability to many compounds.3 Secondly, mycobacteria produce degrading enzymes such as β-lactamases4 and other drug-modifying enzymes. These are among the factors cited to explain the natural resistance of many mycobacterial species …
Mitotic Inhibition of Epidermal Cells From Psoriasis Lesions In Vitro by Extracts From Normal Human Skin2
Authors: D. P. Chopra, B. A. Flaxman
Journal: JNCI Journal of the National Cancer Institute (1973)

Previously it was shown that mitosis of normal human epidermal cells in vitro was regulated in part by a tissue-specific mitotic inhibitor (chalone). The present study demonstrated that epidermal cells from psoriasis lesions, a condition of benign epidermal hyperplasia, were also inhibited by normal skin extract in vitro. This inhibition was tissue specific, since liver extract had no effect. It is concluded that excessive proliferation of psoriatic epidermal cells is not due to failure of target-cell response to epidermal chalone.
Can breathing pattern parameters be differentiated between healthy and severe asthma patients
Authors: Wai Lo, Anne Bruton, Anna Barney
Journal: European Respiratory Journal (2012)

Abnormal breathing patterns during acute episodes of asthma are common. However, little is known about breathing pattern parameters (BPP) in severe asthma (SA) patients during the asymptomatic phase, or how they relate to those in the healthy population.

Aim: To determine which BPP differentiate SA patients from healthy controls.

Method: Ten SA patients and 10 healthy controls were recruited. BPP were monitored over a 30 minute period by respiratory inductive plethysmography. Recorded BPP were: 1. Tidal volume (Vt); 2. Variability in tidal volume (VVt); 3. Expiration time (Te); 4. Symptoms of hyperventilation (SH); 5. End-tidal carbon dioxide (ETCO2). VVt was assessed by coefficient of variation (CV). Time series of breath by breath Vt were inspected for abnormal pattern. SH were assessed by Nijmegen questionnaire (NQ). ETCO2 was monitored by capnography. Differences between healthy controls and SA patients were explored using one-way ANOVA.

Results: Mean NQ score was higher in SA patients than in healthy controls (p=0.00). ETCO2 levels were significantly correlated with NQ score (r =-0.8, p  0.01). Time series analysis revealed sporadic episodes of frequent sighs in both groups. No significant differences between groups for any BPP were identified.

Conclusion: The recorded BPP did not differentiate between the SA patients and healthy volunteers in our small study. The higher SH found in the SA group do not appear to be associated with differences in BPP. This study raised doubt that there is a 'pattern' that is common within the SA population and therefore BPP must be considered on an individual basis.
Renal systems biology of patients with systemic inflammatory response syndrome
Authors: Ephraim L. Tsalik, Laurel K. Willig, Brandon J. Rice, Jennifer C. van Velkinburgh, Robert P. Mohney, Jonathan E. McDunn, Darrell L. Dinwiddie, Neil A. Miller, Eric S. Mayer, Seth W. Glickman, Anja K. Jaehne, Robert H. Glew, Mohan L. Sopori, Ronny M. Otero, Kevin S. Harrod, Charles B. Cairns, Vance G. Fowler, Emanuel P. Rivers, Christopher W. Woods, Stephen F. Kingsmore, Raymond J. Langley
Journal: Kidney International (2015)
Racial disparities in incidence and survival among 37,977 blacks and whites with multiple myeloma.
Authors: A. J. Waxman, P. Mink, S. Devesa, W. F. Anderson, B. M. Weiss, S. Kristinsson, K. McGlynn, O. Landgren
Journal: Journal of Clinical Oncology (2010)

8115 Background: Multiple myeloma (MM) is the most common hematologic malignancy in blacks. Prior studies suggest poorer survival among blacks than whites; however, some smaller hospital-based studies suggest similar survival in equal access health systems. We conducted a large-scale, population-based study to evaluate racial disparities in MM incidence and MM-specific survival. Methods: Data were obtained from the National Cancer Institute's Surveillance, Epidemiology and End Results-9 Registry, covering new diagnoses of MM from 1973-2005 with follow-up through 2006. Age at diagnosis was grouped into three strata (<50, 50-69, and 70+ years). Incidence rates were calculated using SEER*Stat. Cumulative MM-specific survival was assessed by the Kaplan-Meier method and the log-rank test. Results: 37,977 MM patients (5,798 blacks; 28,939 whites) were identified. Mean age at diagnosis was 65.7 years for blacks and 70.0 years for whites (p<0.001). Incidence was 2-fold higher in blacks than whites (10.9 and 4.9 per 100,000 person-years, respectively). This disparity was significantly greater among younger patients (3-fold higher incidence among patients <50 years old). MM-specific survival was better in blacks than whites at 5 and 10 years of follow-up (p<0.001). After the introduction of novel therapies, 5-year MM-specific survival for whites improved (38% in 1973-1979 vs 56% in 2000-2005; p<0.001); significant improvement was not seen in blacks over this period. Conclusions: Our study shows for the first time that, despite a 4-5 year younger average age at MM diagnosis and greater incidence rates, MM-specific survival was greater for blacks than whites. Previously reported excess mortality in blacks is only seen clinically because MM is more common in blacks than whites. These somewhat paradoxical results suggest disease heterogeneity by race. Whites demonstrate a more pronounced survival benefit following recent treatment advances, likely reflecting access disparities; regardless, blacks continue to show superior survival in the era of novel therapies. Further studies are needed to improve our understanding of the molecular basis of these patterns to appreciate disease subtype-specific features. No significant financial relationships to disclose.
Traumatic pseudocyst of the spleen
Authors: P S Sinha, T A M Stoker, N O Aston
Journal: Journal of the Royal Society of Medicine (1999)

Four patients with pseudocyst of the spleen gave histories of abdominal trauma. In one patient the pseudocyst had ruptured, necessitating emergency splenectomy 34 years after the original injury. In a second patient the pseudocyst was discovered incidentally, and was managed by spleen-preserving excision; and the third and fourth presented with abdominal pain and had splenectomy and spleen-preserving surgery, respectively. All patients with conservatively treated splenic injury are at risk of developing a pseudocyst of the spleen, and the lesion can be detected by computed tomography or ultrasound. When there are no symptoms the natural history is unknown; but if surgery is necessary, splenectomy can sometimes be avoided.
Curability of solitary bone plasmacytoma.
Authors: M A Dimopoulos, J Goldstein, L Fuller, K Delasalle, R Alexanian
Journal: Journal of Clinical Oncology (1992)

The effects of involved-field radiotherapy were assessed in patients with a solitary plasmacytoma of bone (SBP).Forty-five consecutive patients with an SBP received megavoltage irradiation of at least 3,000 cGy. The median age was 53 years, 67% of patients showed a myeloma protein, and uninvolved immunoglobulins (Igs) were preserved in 93% of patients.Permanent control of presenting disease was achieved in all but two patients, but 46% of patients developed multiple myeloma. When it occurred, progression of myeloma occurred within 3 years in two thirds of the patients, suggesting that the extent of disease was understaged at diagnosis. Myeloma protein disappeared in nine patients (30%) whose disease has not yet recurred. The median survival for all patients was 13 years and the myeloma-specific survival fraction at 10 years was 53%.In patients with an SBP, the disappearance of myeloma protein with involved-field radiotherapy predicted long-term disease-free survival and possible cure. Nonsecretory disease and persistent myeloma protein after treatment were adverse prognostic factors for which adjuvant therapy with interferon alfa should be considered.
Community-acquired Aspiration Pneumonia in Intensive Care Units
Authors: OLIVIER LEROY, CHRISTIAN VANDENBUSSCHE, CECILE COFFINIER, CHRISTOPHE BOSQUET, HUGHES GEORGES, BENOIT GUERY, DIDIER THEVENIN, GILLES BEAUCAIRE
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Over a 9-yr period, among 505 patients exhibiting severe community-acquired pneumonia and admitted into a total of six medical ICUs in the north of France, we collected 116 patients (23%) meeting the usual criteria for aspiration pneumonia. Main medical grounds of ICU admission were respiratory distress in 54 patients and neurological disturbances in 62 patients. The main underlying risk factor for aspiration pneumonia was drug overdose (39%). Mechanical ventilation was required for 73 patients. Initial shock was present in 15 patients. Pulmonary involvement was bilateral in 27 patients. There were 94 aerobic organisms isolated from 70 patients (60%), the most frequent being gram-negative bacilli (n = 38), Staphyloccus spp. (n = 27) and Streptococcus pneumoniae (n = 22). Overall mortality was 22%, but only 11 (11%) deaths were directly or indirectly related to aspiration pneumonia. Stepwise multivariate analysis identified four independent predictors of mortality: ineffective initial antimicrobial therapy (p = 0.0001), positive initial blood culture (p = 0.0001), hospital-acquired lower respiratory tract superinfections (p = 0.0054), and use of inotropic support (p = 0.0078). The importance of prevention of hospital-acquired superinfections and permanent optimization of our antimicrobial strategies warranting efficacy of the initial antimicrobial therapy is underlined.
Randomized Phase Ii Study of Capecitabine and Cisplatin with or Without Sorafenib in Patients with Metastatic Gastric Cancer: Stargate Study
Authors: Y. Kang, K.H. Lee, L. Shen, K. Yeh, Y.S. Hong, Y.I. Park, S.H. Yang, D.B. Shin, D.Y. Zang, W.K. Kang, I.J. Chung, Y.H. Kim, B. Ryoo, S.R. Park, B. Nam, M.H. Ryu
Journal: Annals of Oncology (2014)
Development of a 950-gene DNA array for examining gene expression patterns in mouse testis
Authors: John C Rockett, J Christopher Luft, J Brian Garges, Stephen A Krawetz, Mark R Hughes, Kwan Hee Kirn, Asa J Oudes, David J Dix
Journal: Genome biology (2001)

Over the past five years, interest in and use of DNA array technology has increased dramatically, and there has been a surge in demand for different types of arrays. Although manufacturers offer a number of pre-made arrays, these are generally of utilitarian design and often cannot accommodate the specific requirements of focused research, such as a particular set of genes from a particular tissue. We found that suppliers did not provide an array to suit our particular interest in testicular toxicology, and therefore elected to design and produce our own. We describe the procedures used by members of the US Environmental Protection Agency MicroArray Consortium (EPAMAC) to produce a mouse testis expression array on both filter and glass-slide formats. The approaches used in the selection and assembly of a pertinent, nonredundant list of testis-expressed genes are detailed. Hybridization of the filter arrays with normal and bromochloroacetic acid-treated mouse testicular RNAs demonstrated that all the selected genes on the array were expressed in mouse testes. We have assembled two lists of mouse (950) and human (960) genes expressed in the mouse and/or human adult testis, essentially all of which are available as sequence-verified clones from public sources. Of these, 764 are homologous and will therefore enable close comparison of gene expression between murine models and human clinical testicular samples.
Diallylnitrosamine: A Potent Respiratory Carcinogen in Syrian Golden Hamsters: Brief Communication2
Authors: J. Althoff, C. Grandjean, B. Gold
Journal: JNCI Journal of the National Cancer Institute (1977)

Diallylnitrosamine (DAN), one of the few nitrosamines tested thus far that has not induced neoplasms in rats, caused a high Incidence of respiratory tract tumors in Syrian golden hamsters treated sc with single or weekly doses of the compound. The effect was dose-dependent. The nasal cavity, larynx, and trachea were the most affected by DAN; most drug-induced tumors at those sites were adenocarcinomas and papillary polyps.
Personalized management of patients with inoperable alveolar echinococcosis undergoing treatment with albendazole: usefulness of positron-emission-tomography combined with serological and computed tomography follow-up
Authors: J. Crouzet, G.A. Mantion, T. Thevenot, V. Di Martino, S. Bresson-Hadni, F. Grenouillet, R. Piarroux, E. Delabrousse, O. Blagosklonov
Journal: Clinical Microbiology and Infection (2009)