tbuckley/cabot-search huggingface dataset:
Correlation of ABI1 and PTEN expression during prostate tumor progression.
Authors: Leszek Kotula, Anita Hryniewicz-Jankowska, Xiang Li, Katarzyna Augoff, Csaba Papp, Disharee Das, Sonia H.Y. Kung, Ladan Fazli, Tamara Jasmaspishvili, David Monty Berman, Fan Zhang, Baylee Porter, Aleksander Sikorski, Martin Gleave, Vladimir Kuznetsov, Gennady Bratslavsky
Journal: Journal of Clinical Oncology (2022)

172 Background: Mechanisms of tumor invasion are not well defined. PTEN, a key tumor suppressor frequently inactivated in epithelial cancers, acts as a central node that controls tumor invasion. Despite PI-3 kinase-phospho-Akt pathway activation resulting in enhanced tumor growth, prostate tumors with PTEN loss undergo p53-mediated senescence that restricts tumor invasion. Methods: ABI1 downregulation is associated with epithelial-mesenchymal transition in highly invasive prostate tumors; these tumors frequently loose PTEN; therefore we set to examine genetic interaction of ABI1 and PTEN using novel mouse model of prostate cancer. We analyzed the correlation of ABI1 and PTEN expression in human PCa tumor tissue. Results: Here, using Abi1/Pten KO mouse model we identified a novel mechanism that guards tumor invasion. In Pten-null tumors upregulation of Abi1 leads to sequestration of activated Src kinase. In the absence of Abi1, this regulation is lost leading to activation of non-canonical WNT-SRC-STAT3 axis and enhanced invasion through activation of MMP2 activity. This molecular mechanism explains progression of tumors with Pten loss from PIN to invasive carcinoma upon concomitant Abi1 inactivation. In human tumors with low Abi1 and Pten are associated with aggressive phenotype, biochemical recurrence and metastasis. Conclusions: ABI1 acts as failsafe mechanism in PTEN null tumors by restricting SRC-mediated tumor invasion. ABI1 might have a predictive value in clinical setting in context of PTEN levels.
Chancroid.
Authors: A. Mindel
Journal: BMJ (1989)

<h3>Summary</h3> The pathogenesis of encephalopathy-associated Covid-19 is still unclear. Multimodal brain MRI in 25 Covid-19 patients with neurological symptoms revealed angiographic and brain perfusion changes suggesting an under-recognized dysregulated brain perfusion not identified by morphological neuroimaging alone. Endothelial dysfunction, a key pathomechanism of dysregulated brain perfusion, may contribute to central-nervous-system disturbances in Covid-19.
Acute Rheumatism
Authors: J. A. Glover
Journal: Annals of the Rheumatic Diseases (1946)

<h3>Summary</h3> Signal transduction at vertebrate excitatory synapses involves the activity of ionotropic glutamate receptors, including the AMPA (α-amino-3-hydroxy-5-methyl-4-isoaxazole propionate) receptor. Technical advances in cryo-electron microscopy have brought a slew of full-length structures of AMPA receptors, on their own and in combination with auxiliary subunits. These structures illustrate a wide range of conformations, indicating that individual domains might undergo substantial lateral and rotational motions during gating. Here, we used bifunctional methanethiosulfonate cross-linkers to calibrate the conformations that occur in functional AMPA receptors both in the presence and absence of the auxiliary subunit Stargazin. Our data indicate that receptors without auxiliary subunits have considerably more conformational freedom and can get trapped in relaxed conformations. In contrast, Stargazin maintains both activated and desensitized receptors in compact arrangements. Thus, auxiliary subunits not only change the kinetics and trafficking of receptors, but also restrict their structural dynamics.
Tailoring 4Kscore thresholds to multiparametric MRI results.
Authors: Daniel R Nemirovsky, Akshay G Reddy, Benjamin McSweeney, Charles Klose, Joyce Chen, Matthew Atienza, Shawn Haji-Momenian, Danish Imtiaz, Michael Joseph Whalen
Journal: Journal of Clinical Oncology (2022)

31 Background: 4Kscore was developed and validated agnostic to prostate multiparametric MRI (mpMRI) findings, with current clinical paradigms utilizing a value of 7.5% to delineate the potential for high-grade disease. A growing body of evidence suggests improved diagnostic utility when used in conjunction with mpMRI results. Incorporation of mpMRI PIRADS scores may have potential to enhance diagnostic accuracy of 4Kscore, especially for non-definitive lesions. This study aims to examine the optimal 4Kscore threshold in PIRADS 3/4 lesions to maximize test utility and help guide clinical decision-making. Methods: A single-institution review of all patients with recorded 4Kscore, prostate MRI with dominant PIRADS 3/4 lesions, and final biopsy pathology from 2016-2020 was conducted from an IRB-approved database. Clinically significant prostate cancer (csPCa) was defined as Gleason score ≥3+4 on final biopsy. Receiver operating characteristic curves were generated, and the primary data point was chosen to maximize sensitivity and specificity. Results: 88 patients with dominant PIRADS 3 (n = 40) or PIRADS 4 (n = 48) lesions were identified. For patients with PIRADS 3 lesions, area under the curve (AUC) was 0.8083 (p &lt; 0.0039) with optimal 4Kscore threshold to detect csPCa as 18.5% (sensitivity = 70.00%, specificity = 80.00%). Negative predictive value (NPV) at 4Kscore of 18.5% in PIRADS 3 lesions was 0.93. In patients with dominant PIRADS 4 lesions, AUC was 0.7735 (p &lt; 0.002), and optimal threshold to detect csPCa was 21.5% (sensitivity = 70.59%, specificity = 76.67%). NPV at 4Kscore of 21.5% in PIRADS 4 lesions was 0.82. Conclusions: Stratification of mpMRI PIRADS 3/4 lesions suggests that utilization of more permissive 4Kscore thresholds can improve prediction of csPCa without sacrificing NPV, especially for PIRADS 3 lesions. These findings may enhance risk-adapted prostate cancer screening, reduce unnecessary prostate biopsies, and optimize clinical management.
Abstract 17174: Discrepancies in Development of Cardiac Myopathy in Males vs. Females
Authors: Gagandeep Kaur, Mobin Kheirkhahan, Nassir F Marrouche
Journal: Circulation (2018)

Introduction: Heart disease has proven to be the leading cause of mortality in women. Sudden Cardiac Death being responsible for 1 in 4 female deaths, of these women 64% display no prior symptoms. Structural remodeling associated with fibrosis, however, has been strongly linked to development of cardiovascular disease (CVD), risk factors, and co-morbidities. This study aims to provide a preliminary assessment of fibrosis manifestation in women in comparison to their male counterparts. Methods &amp; Results: Atrial Fibrillation (AF) patients (370 male, 197 female) with Late-Gadolinium Enhanced MRIs (LGE-MRI) were processed for fibrosis. Collected data included: CHADS-VASc factors, age and AF type. These two groups were matched in terms of cardiovascular co-morbidities. The LGE-MRI pre-ablation showed women had significantly higher LA fibrosis than men (17.2 ± 9.5 vs 14.6 ± 7.6, p &lt;0.001), this difference remained true even after stratifying based on Paroxysmal (women 15.6 ± 7.9 vs men 13.8 ± 6.5, p =0.04) and Persistent types of AF (women 19.9 ± 11 vs men 15.3 ± 8.4, p =0.002). Women at the time of LGE-MRI scan were older (72.2 ± 11.1 vs 67.8 ± 11.6, p &lt;0.001) and a majority of them were older than 75-years-old (40.1%), whereas the majority of men were 65 to 74-years-old (41.6%). After adjusting for age, the result of our regression model showed female gender contributes to 3.5% more LA fibrosis (CI 95% 0.53 - 6.6%, p =0.02). Conclusions: Given the obtained results, it can be concluded that women should be screened for cardiac symptoms starting at an early age. Women present with CVD symptoms at an older age along with higher fibrosis percentage at their initial visit in comparison to their male counterpart. Further research is recommended to determine what factors are associated to this discrepancy.
Abstract 17087: Competent p53 Stabilized iPS-Cardiomyocyte Transplantation in Ischemic Myocardium of Mice Reduce Fibrosis Through Exosomal miRNA-26a
Authors: Ramaswamy Kannappan, Jessica M Miller, Nikhil M Mardhekar, Jianyi Zhang
Journal: Circulation (2018)

Introduction: With the growing field of myocardial repair through transplantation of cardiomyocytes (CM) derived from human induced pluripotent stem cells (iPSC) calls for a method for reducing fibrotic tissue development at the site of cell transplantation. We tested the hypothesis whether transplanting CMs derived from p53 stabilized (p53S) iPSCs could reduce the recruitment of fibroblast and reduce fibrosis at the site of transplantation. Methods: Transcription factor p53 functions are inflammation dependent: inducing apoptosis in inflammatory and transformed cells while promoting cell cycle in normal cells. Utilizing this discriminating nature of p53 we selected iPSCs that express less inflammatory and more anti-inflammatory markers and differentiated them into CM. Control CM (ctrl-CM) and p53S-CMs were tested for transplantation induced fibrosis in a mice model. Results and Discussion: The inflammatory markers such as accumulation of ROS, superoxide and DNA damage were significantly lesser in p53S cells. RNA sequencing revealed that, in p53S-CMs, the anti-inflammatory and anti-fibrosis signaling pathways are upregulated compared to ctrl-CMs. Transplantation of both CMs into the myocardium of ischemia induced mice resulted in cell engraftment and fibrosis around the transplantation site. However, fibrotic area was significantly reduced in p53S-CM transplanted sites evidenced by COL1 and COL4 accumulation and Sirus red staining of fibrotic tissue. In vitro treatment of human fibroblast with p53S-CM exosomes (p53S-Exo) resulted in reduced expression of fibrotic markers than ctrl-CM exosomes (Ctrl-Exo) treatment. miRNA analysis of exosomes showed that the anti-inflammatory miRNA26a is upregulated and the inflammatory miRNA101 is downregulated in p53S-Exo. Overexpression of miRNA26a mimic in ctrl-Exo abrogated the fibrosis inducing property of ctrl-Exo. Interestingly, in migration study, fibroblasts preferentially migrated towards the ctrl-CMs. Conclusion: Our results clearly shows that anti-inflammatory cells can be isolated from a population of heterogeneous cells by activating p53. Transplanting p53S-CMs attracted reduced fibroblast to the engraft site and oppose fibrosis through exosomal expression of miRNA26a.
The Practitioner's Library of Medicine and Surgery
Journal: JAMA (1935)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 17244: Atrial Fibrillation is Associated With Day 90 Mortality in Patients Undergoing Bone Marrow Transplant
Authors: Matthew Subramani, Anita D’Souza, Jason Rubenstein
Journal: Circulation (2018)

Introduction: Atrial fibrillation often occurs after bone marrow transplant (BMT) and has been shown to increase hospital stay and other morbidity. Treatment can be complicated due to contraindications to anticoagulation therapy. Our objective was to describe the incidence of atrial fibrillation in patients within the first 90 days after BMT and risk predictors for overall mortality. Methods: Patients with active malignancy undergoing BMT in 2016 at the Medical College of Wisconsin were included (n=259). Medical records were reviewed for baseline patient characteristics, atrial fibrillation risk factors, incidence of atrial fibrillation, and other complications. Patients were categorized based on survival at 90 days post-BMT. Baseline characteristics and risk factors were analyzed to determine if there was an association with the development of atrial fibrillation and all cause mortality at 90 days. Results: Overall, 10.4% developed atrial fibrillation within the first 90 days after BMT. Of those that died before 90 days, 33.3% developed atrial fibrillation compared to 9.6% in those who survived (OR 4.7, 1.11-20.13 p=0.04). Those that died before 90 days were also more likely to have heart failure with reduced ejection fraction, prior radiation therapy (XRT), undergo cardioversion, and to be started on an antiarrhythmic drug (Table 1). When all significant univariate variables were included in a multivariate regression, only XRT was independently predicative of mortality (OR 11.5, 2.4-54.9, p=0.002). The development of atrial fibrillation significantly predicted early mortality (Log Rank p=0.009). Conclusion: This analysis demonstrated that the development of atrial fibrillation was predictive of early post-transplant all cause mortality. XRT and antiarrhythmic drug use also significantly predicted mortality. Further studies are required to determine if there is a mortality benefit to the prevention of atrial fibrillation in patients after BMT.
Renin, aldosterone, the aldosterone-to-renin ratio, and incident hypertension among normotensive subjects from the general population
Authors: Natalie Arnold, Iris M Hermanns, Andreas Schulz, Omar Hahad, Volker H Schmitt, Marina Panova-Noeva, Jürgen H Prochaska, Harald Binder, Norbert Pfeiffer, Manfred Beutel, Karl J Lackner, Thomas Münzel, Philipp S Wild
Journal: Cardiovascular Research (2022)

To investigate the predictive ability of direct plasma renin and aldosterone concentrations as well as their ratio [aldosterone-to-renin (ARR)] for incident hypertension in the general population.Concentration of renin and aldosterone were measured by a chemiluminescence immunoassay using the fully automated LIAISON® platform (DiaSorin) among 5362 participants of the population-based Gutenberg Health Study, who were normotensive and had no clinically overt cardiovascular disease at baseline. During a follow-up period of 5 years, 18.6% (n = 996) developed a new-onset hypertension. Comparing extreme quartiles of biomarker distribution, the relative risk (RR) for incident arterial hypertension was found to be 1.58 [95% confidence interval (CI) 1.25-2.00; P = 0.00015; Q1 vs. Q4ref] for renin; 1.29 (95% CI 1.05-1.59, P = 0.018; Q4 vs. Q1ref) for aldosterone and 1.70 (95% CI 1.33-2.12; P < 0.0001; Q4 vs. Q1ref) for ARR after multivariable adjustment in men. In females, only high ARR was independently predictive for incident hypertension over 5 years [RR 1.29 (95% CI 1.04-1.62); P = 0.024]. Even in the subgroup of individuals having biomarker concentrations within the reference range, high ARR was predictive for new-onset hypertension in men [RR 1.44 (95% CI 1.13-1.83); P = 0.003]. Finally, synergistic effects of co-prevalent obesity and ARR on incident hypertension were also demonstrated, resulting in markedly higher risk estimates as seen for biomarker alone [RR of 2.70 (95% CI 2.05-3.6) for Q4 of ARR and having body mass index ≥ 30 kg/m2 vs. low ARR (Q1ref) and normal weight; P < 0.0001].Among normotensives from the general population ARR possesses a stronger predictive value for incident hypertension than renin or aldosterone alone. The prediction of arterial hypertension by ARR was even stronger in obese subjects.
Scurvy
Authors: H. R. C. Riches
Journal: BMJ (1954)

MEDICAL MEMORANDA CBJORALkg.) of body weight gave adequate resistance.Apart from its influence on the dosage, however, the time factor is of importance, since it appears that immunization, to be effective, should be given earlier than six days before the onset of symptoms.Although gamma globulin has been used to control out- breaks of infective hepatitis in America, this appears to be the first occasion on which it has been used in this country.Indeed, as yet there has been no evidence to indicate that gamma globulin obtained from blood donors here contains sufficient antibodies to be of any imrmunizing value.The outbreak described, while in no way proving the efficacy of gamma globulin, does, however, suggest that it is a potent agent in controlling the spread of infective hepatitis.This is of considerable economic value in closed communities where infective hepatitis entails the restriction of admissions; and it may be that increased supplies will enable the use of gamma globulin as a protective agent to be more fully exploited in the future.I should like to thank Dr. C. M.
Diphtheria
Authors: E. Penny
Journal: BMJ (1886)

THE BRITISH MEDICAL JOURNBAL.1i healthy.The mental faculties are perfect.He has no couigh, diar- rhwa, or perspirations; no pyrexia or hedtic.-.REMA1X8S.*-!-The above is a tpical cUel of 'mollities: ots8Wnt.
Efficacy and Safety of Atorvastatin in the Prevention of Cardiovascular End Points in Subjects With Type 2 Diabetes: The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN)
Authors: Irene F. Gazi, Dimitri P. Mikhailidis
Journal: Diabetes Care (2006)

vasive and cost-free clinical screening tool.
The Croonian Lectures on Cerebral Localisation
Authors: D. Ferrier
Journal: BMJ (1890)

LBCTIRB IV.-TrB AUDITORY OENTIBE.MB. PILBSTDBNT AND GBNTLEMN,-AmoDg the reactions conse- quent upon electrical stimulation of the cortex there is one, or rather an assemblage of reactions, which might almost be con- sidered of itself indicative of the existence of subjective auditory sensation-a& reaction which guided me in my first attempts to de- fine the auditory sphere by the destructive method.The reaction in question is that which occurs on irritation of the superior tem- poral convolution and its homologues in the lower vertebrates: namely, quick retraction or pricking of the opposite ear, aesoci- ated frequently with opening of the eyes, dilatation of the pupils, and turning of the head and eyes to the opposite side.These are
Identifying patient profiles and mapping the patient journey across three countries in a large-scale, fully digital survey of patients with prostate cancer.
Authors: Alicia K. Morgans, Reiner Lehmann, Axel Heidenreich, Stephen Allen, Ernst-Günther Carl, Howard Wolinsky, Andreas Poschenrieder, Osvaldo Mirante, Joe M. O'Sullivan
Journal: Journal of Clinical Oncology (2022)

16 Background: A survey of patients with prostate cancer (PCa) was conducted to map their experiences, expectations and attitudes, and to identify challenges and unmet needs in diagnosis, therapy patterns, care teams, quality of life (QoL), patient organizations and resources. Here, we describe the initial survey results and explore differences in diagnosis and therapy patterns between 3 countries. Methods: Don’tBePatient Intelligence conducted a large survey in patients with non-metastatic (M−) and metastatic (M+) PCa in Germany (DE), the UK and the US from Feb 9–Apr 10, 2021 in collaboration with patient organizations and medical experts. Recruitment was through social media advertising and patient organizations. Data were evaluated using descriptive and advanced statistics. Results: Of 33,882 survey starters, 15,824 completed, split 50.1%/49.9% in rural/urban areas. In DE/US, diagnosis through healthcare screening was more frequent than in the UK (M−/M+: DE 77%/58%; UK 42%/21%; US 77%/63%) where a higher percentage of symptomatic diagnosis was recorded (M−/M+: DE 18%/39%; UK 49%/75%; US 12%/31%). Prostatectomy was the predominant therapy in M− PCa in DE/US (71%/57%). In the UK, radiotherapy was slightly more frequent than prostatectomy (48% vs. 41%) and active surveillance was more common than in DE/US (14% vs. 6%/9%). Hormone therapy was the most common therapy in M+ PCa in all countries (DE 65%; UK 77%; US 73%). Chemotherapy was received by &lt; 2% of patients with M− PCa in all countries but was more frequent in M+ PCa in the UK than DE/US (38% vs. 21%/27%; table). Satisfaction levels were generally high (&gt; 80%) for all therapies in all countries. Conclusions: To our knowledge this is the largest digital survey conducted in patients with PCa, allowing identification of unmet needs in the patient journey. Preliminary data suggest that rates of screening are lower in the UK than DE/US; this may correlate with the higher rate of symptomatic and potentially later-stage diagnosis, highlighting the role of routine screening. Relatively low active surveillance rates in DE/US may reflect a lower likelihood of men with M− versus M+ PCa to respond to the survey. Further analyses will include impact of differences in patient journey, trust in healthcare professionals, access to information, involvement with patient advocacy groups and QoL. [Table: see text]
Medical College Hospital, Calcutta
Authors: S. G. Chuckerbutty
Journal: BMJ (1862)

says: " If the fracture is simple, and there is no wound in the scalp and no symptoms of injury to the brain, it would be the worst practice in the world to make an incision into the part, and perform the operation of trephining; for by this m"eans you make what was before a simple, a compound fracture.If the fracture, how- ever, be compound, the treatment mnust be very dif- ferent, because a compound fracture is followed very generally by inflammation of the brain; and it will be of no use to trephine when inflammation is once formed; in these cases, it is necessary to trephine."The treat- ment, however, of the surgeons of the present day is not in strict accordance with this rule, especially as re- gards child-en; the " expectant practice" is more adopted.During the last few years, two cases very mnuch resembling the preceding have been admitted into tile wards of St. George's Hospital: the one a little girl, under the care of Mlr.Hawkins; the other a boy, under Mr. Johnson.In both there was a compound fracture of the skull, with considerable depression; in both, there was a total absence of all symptoms of com- pression; in both, operative measures were not resorted to; and both made a good recovery.This line of prac- tice, however, should not be relied on too implicitly; in fact, in this, as in every other class of cases, the surgeon must be guided to a certain extent by the circumstances of the case.
Factors Affecting Yield of Genetic Testing of Sudden Deaths in Young Individuals
Authors: Christopher C. Cheung, Zian H. Tseng
Journal: JAMA Cardiology (2022)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Cardiology journal