tbuckley/cabot-search huggingface dataset:
Carbon‐Quantum‐Dots‐Loaded Mesoporous Silica Nanocarriers with pH‐Switchable Zwitterionic Surface and Enzyme‐Responsive Pore‐Cap for Targeted Imaging and Drug Delivery to Tumor
Authors: Zhongning Liu, Xin Chen, Xiaojin Zhang, John Justin Gooding, Yongsheng Zhou
Journal: Advanced Healthcare Materials (2016)

Mesoporous silica nanocarriers with pH-switchable antifouling zwitterionic surface, enzyme responsive drug release properties and blue fluorescence are reported. Prolonged circulation in the blood system with zero premature release as well as efficient cellular uptake and intracellular drug release in tumor tissue are achieved.
Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), ERCC1, & thymidine phosphorylase gene expression in primary & metastatic (met) colorectal cancer (CRC) tissue in patients (pts) treated on a phase I trial of oxaliplatin (OX) & capecitabine (Xel)
Authors: J. L. Grem, K. Uchida, D. Salonga, P. Danenberg, K. Danenberg
Journal: Journal of Clinical Oncology (2005)

3549 Background: Overexpression of TS/DPD & ERCC1 in tumor tissue have been associated with insensitivity to 5-FU and OX therapy, respectively, while high TP levels predict for increased sensitivity to Xel. Methods: When feasible, biopsies of met tumor were taken in pts before OX (130 mg/m2 d1)/Xel (1200–3000 mg/m2 d1–5,8–12) q 3wk. Microdissected met & archival primary tumors were analyzed for gene expression (vs b-actin) of these 4 targets by real-time QRT-PCR. Survival (Surv) & time to treatment failure (TTF) were analyzed by log-rank. Gene expression v outcome was assessed using median (med), 25th & 75th percentiles for each target. Results: 90 pts participated. The med # prior chemotherapies was 2; 96% had prior 5-FU; 78% had prior irinotecan. Med mRNA levels were higher in met v primary tumor (table); rank sum analysis of paired samples showed (med): TS, 4.2 vs 2.2, p<0.001; DPD, 1.7 vs 0.4, p=0.005; ERCC1, 2.3 vs 1.1, p=0.002; TP, 6.3 vs 3.9 p=0.018. Pts whose tumor had ERCC1 >75th % had shorter TTF (med 162 d vs 85 d, p=0.026); pts with TP >75th % tended to have longer TTF (med 194 d vs 146 d, p=0.072). Individual mRNA levels in met tumor did not correlate with Surv, but pts whose tumors had both TS & ERCC1 < med had longer Surv (med 502 vs 296 days, p=0.038). Conclusions: In this study, target gene expression in primary tumor did not reflect levels in met tissue. In pre-treated CRC pts, mRNA levels of TP & ERCC1 in met tumor had some predictive value for TTF with OX/Xel therapy. Low levels of TS & ERCC1 predicted for improved Surv. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics, Sanofi-Synthelabo Response Genetics
Reducing the Burden of Hypertension
Authors: Nathan D. Wong, Stanley S. Franklin
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
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Authors: Salvatore Petta, Antonio Craxì
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. Reply: We recently reported that, in a large cohort of biopsy‐proven patients with nonalcoholic fatty liver disease (NAFLD), severe steatosis, diagnosed by histology or by ultrasound (US), is independently linked to increased liver stiffness measurement (LSM) values. As a consequence, we reported higher rates of false‐positive LSM results for the noninvasive assessment of F2‐F4 and F3‐F4 fibrosis by transient elastography in patients with severe steatosis compared with their counterparts.1 Accordingly, we suggested that, in NAFLD patients, the presence of severe steatosis, per se or evaluated by US, should always be taken into account in order to avoid overestimations of liver fibrosis.1 Notably, we reported similar results in the setting of chronic hepatitis C patients as well.2 We thank Eddowes et al. for their interest in our study.1 First, we agree with the authors that a high skin to capsule distance (SCD), typical of obese individuals, could lead to an overestimation of LSM. However, when excluding obese NAFLD patients from our analysis, in the 156 nonobese ones with F0‐F2 fibrosis and with presumed lower SCD, we confirmed significant higher LSM in those with severe histological steatosis compared to those without (7.3 ± 3.1 vs. 6.0 ± 2.0; P = 0.007). Second, nevertheless, as expected, patients with severe steatosis tend to have higher degrees of fibrosis, in Supporting Fig. S1 we clearly showed that when stratifying patients according to the singular stage of fibrosis (F0 alone, F1 alone, and F2 alone), individuals with severe steatosis have higher LSM compared to those without. Finally, in response to Eddowes et al., we clarify that in order to explore factors other than fibrosis affecting LSM in NAFLD, in the linear multivariate model predicting LSM, we included variables significant at univariate analysis and quality criteria known to impact on LSM, such as biopsy length and interquartile range/median value. This analysis clearly showed an independent effect of steatosis on LSM. This effect was also clearly demonstrated in Table 3, where among patients with F0‐F1 or F0‐F2 fibrosis, after stratifying for ballooning and/or for lobular inflammation, we confirmed significantly higher LSM in patients with severe steatosis compared to those without in almost all the tested subgroups. Anyway, according to the request of the authors, we confirmed the independent association of steatosis (P = 0.04) with higher LSM also after correction for fibrosis. In conclusion, we are fully confident about the strength of our results. So, consistent with our data, we are working on evaluating whether adjusting LSM for controlled attenuation parameter—a noninvasive tool measured by FibroScan and predicting steatosis—is useful in improving the diagnostic performance of LSM for fibrosis in NAFLD.
Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition
Authors: Scott A. Hubers, Nancy J. Brown
Journal: Circulation (2016)

Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiological mechanisms of heart failure: activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared with enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension.
Abstract 249: Neonatal Mouse Hearts Do Not Regenerate after Severe Cryoinjury
Authors: Ching-Ling (Ellen) Lien, Ali Darehzereshki
Journal: Circulation Research (2013)

Introduction: In contrast to adult zebrafish, mammalian adult hearts cannot regenerate in response to tissue damage. Interestingly, neonatal mouse hearts have regenerative capacity similar to adult zebrafish after ventricular resection. Zebrafish hearts regenerate in a similar manner after cryoinjury compared to other injury types (ventricular resection and genetic ablation); however scar tissue forms and it takes much more time to resolve the scar and regenerate after cryoinjury. It remains to be determined if neonatal mouse hearts regenerate after cryoinjury, which is thought to be the injury model most similar to damage caused by infarction than resection. Hypothesis: Neonatal mouse hearts respond to different types of injuries differently; there might be a limit to the regenerative capacity of neonatal mouse hearts. Methods: To determine if neonatal mouse hearts respond to different types of injuries differently, we established a cryoinjury model by utilizing a cryoprobe pre-chilled in liquid nitrogen placed at the anteriolateral ventricular wall. At different time points, cardiac functions were determined and the hearts were collected for histological analysis. Results: In contrast to ventricular resection, neonatal mouse hearts fail to regenerate at 21, 60 and 120 days after severe (transmural) cryoinjury. Minimum scar tissues remain after mild (non-transmural) cryoinjury. Echocardiography showed severe impairment of cardiac functions after severe cryoinjury. Epicardial activation and new coronary vessel formation occured after cryoinjury. However, we did not observe increased cardiomyocyte proliferation after severe cryoinjury; this is consistent with the finding that neonatal mouse hearts regenerate after ventricular resection by cardiomyocyte proliferation. When neovascularization is blocked by induction of a VEGF-sequestering soluble receptor (sVEGFR1), neonatal mouse hearts cannot survive after severe cryoinjury and form a more extensive scar following a mild cryoinjury. Conclusion: Neonatal mouse hearts do not regenerate after severe transmural injury due to failure to undergo cardiomyocyte proliferation. Furthermore, neovascularization is essential for the survival and heart regeneration of neonatal mice.
Another way to learn about teaching: What dogs can tell us about the evolution of pedagogy
Authors: Angie M. Johnston, Katherine McAuliffe, Laurie R. Santos
Journal: Behavioral and Brain Sciences (2015)

Abstract Kline argues that it is crucial to isolate the respective roles of teaching and learning in order to understand how pedagogy has evolved. We argue that doing so requires testing species that learn from pedagogy but that rarely teach themselves. Here, we review how one previously neglected species – domesticated dogs ( Canis familiaris ) – may allow researchers to do just that.
Human studies at <i>JEM</i>: Immunology and beyond
Authors: Jean-Laurent Casanova, Carl F. Nathan, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2016)

Since its inception in 1896, The Journal of Experimental Medicine ( JEM ) has aimed to publish outstanding and enduring studies in medical biology, with an emphasis on pathogenesis ([Welch, 1896][1]). The founding editors and their successors have strived to provide a prestigious platform for the
Should surveillance be considered the standard of care in stage I seminoma?
Authors: P. R. Warde, P. Chung, J. Sturgeon, T. Panzarella, M. Giuliani, B. Tew-George, M. Jewett, A. Bayley, M. Moore, C. Catton, M. Gospodarowicz
Journal: Journal of Clinical Oncology (2005)

4520 Background: Standard management for patients with stage I seminoma is adjuvant radiotherapy to the para-aortic ± ipsilateral pelvic lymph nodes. Over the past decade, surveillance has become more accepted but, despite the documented increased risk of second malignancies with adjuvant RT, it has not become widely accepted. This is partly because of the lack of long-term outcome data from surveillance series. We reviewed all patients with stage I disease over a 21 year period to compile information on outcomes in patients managed with these two approaches. Methods: 704 patients with stage I seminoma were seen at our institution between January 1981 and December 2002. Of those, 421 were placed on surveillance and 283 received adjuvant RT. Patient preference determined management approach. The median follow-up was 9.2 years (surveillance 8.1 years, adjuvant RT 10.2 years). Results: Of 421 patients on surveillance, 64 relapsed giving a 5 year relapse rate of 14.5%. The predominant site of relapse was the para-aortic lymph nodes alone in 57 patients (89%). Forty-eight (75%) of these relapses were were managed by RT, 14 with chemotherapy, and 2 with surgery. Of the 48 patients managed with RT for first relapse, 5 developed a second relapse and were salvaged with chemotherapy. The actuarial risk of requiring chemotherapy for treatment of first or second relapse on surveillance was 4.6% at 10 years. Of 283 patients who received adjuvant RT, 14 patients have relapsed giving a 5 year relapse rate of 4.9%. Of those, 10 (3.6%) were managed with chemotherapy, 3 with RT (inguinal recurrences), and 1 with surgery. The actuarial rate of requiring chemotherapy for treatment of relapse for patients managed with adjuvant RT was 3.9% at 10 years. In the whole series, only 1 patient has died of recurrent seminoma having relapsed on surveillance and failed salvage chemotherapy. Conclusions: Surveillance policy for stage I seminoma allows 85% of patients to avoid unnecessary RT. No increase in the number of patients who require chemotherapy has been observed. Given the documented risk of second malignancy associated with adjuvant RT, surveillance should be considered the standard of care with stage I seminoma. No significant financial relationships to disclose.
Bisphosphonates beyond five years
Authors: Zoe Paskins, Louise Warburton
Journal: BMJ (2016)

#### What you need to know

A 74 year old woman experienced a low impact Colles’ fracture five years ago and was started on a bisphosphonate. At her medication review she discusses for how long she should continue.

Recommendations suggest that bisphosphonate prescription is reviewed at five years.1 2 Explore the patient’s risk factors, tolerance, and adherence. Discuss the benefits, harms, and uncertainties of treatment beyond five years and agree a plan of action.

Re-evaluate the patient’s fracture risk by updating the patient’s history. Revisit the patient’s risk factors for fracture. Check for relevant comorbidities that may have developed since her last review such as rheumatoid arthritis. Review her medication for drugs such as corticosteroids and aromatase inhibitors for breast cancer that increase the risk of fracture.

Have other fractures occurred over the past five years? Explore the possibility of undiagnosed vertebral fracture. A history of thoracic back pain or height loss of more than 4 cm may suggest vertebral …
A Case of Penetrating Atherosclerotic Ulcer Treated With Thoracic Endovascular Aortic Repair
Authors: Akiko Soyama, Tatsuji Kono, Tomohiro Matsuoka, Kaoru Otsuka, Shogo Murakami, Hikari Tsuji, Kazuhisa Sakamoto, Kenji Minakata
Journal: Circulation (2015)
Knowledge of prescription medications among elderly cancer patients.
Authors: L. Chew, E. H. Si, J. Ng, R. Yap, K. N. Koo, V. Shih, D. Poon
Journal: Journal of Clinical Oncology (2010)

e19548 Background: Studies have shown that the elderly do not possess essential knowledge about the medications they consume. This may lead to many problems such as increased medications errors, adverse effects, morbidity and mortality. This study aims to determine how knowledgeable elderly cancer patients (>65 years old) are of their prescription medications and identify areas of needs for safe medication use. Methods: This is a study of elderly patients attending outpatient clinics at the National Cancer Centre Singapore. Patients were interviewed on their prescription medications, indication for use and safe medication use practices. Informed consent was taken prior to initiation of survey and conducted in language understood by patients. Medications and dosages were verified through the electronic records and patients' pharmacies. Results: A total of 196 elderly patients were interviewed. The mean age (SD) of the subjects was 71 (4.6) years. Patients took an average of four (range: 1-14) prescription medications at home. Seventy-four (37.8%) patients missed to mention at least one of their prescribed medications. Most patients correctly identified the prescribed indications for use (87.4%), prescribed doses (91.9%) and dosing frequencies (87.9%). However, few patients could name their medications (19.6%) and few were aware of precautionary instructions for use (32.1%). Survey on safe medication practices showed majority (93.4%) of patients could identify the medications they are allergic to. Almost half of patients would read drug labels (50.8%), discard medication when no longer needed (59.9%) and check expiry dates (44.0%). More than a third would check with prescribers for changes in new prescription (41.3%). Only few patients would keep a medication list (15.4%). Conclusions: A majority of our elderly cancer patients have good understanding of their prescribed medications. However, many of them do not keep a list of medications they are taking, do not always read drug labels or check the expiry dates. Communication between healthcare providers and patient, patient education and medication aids and referral for medication review could improve medication safety in this age group. No significant financial relationships to disclose.
Depressions secondary to other psychiatric disorders and medical illnesses
Authors: G Winokur, D W Black, A Nasrallah
Journal: American Journal of Psychiatry (1988)

The authors studied 401 patients with depressions secondary to psychiatric illnesses (substance abuse disorders or somatoform, anxiety, or personality disorders) or depressions secondary to medical illnesses. They found that the patients with depressions secondary to psychiatric illnesses had an earlier age at onset, were more likely to have suicidal thoughts or to have made suicide attempts, were less likely to have memory problems, were less improved with treatment and more likely to relapse on follow-up, and had more alcoholism in their families than patients with depressions secondary to medical illnesses. Depressions secondary to medical illnesses seem to fit the category of reactive depression, and depressions secondary to psychiatric illnesses fit the definition of neurotic depression.
A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach
Authors: John G. Hanly, Li Su, Murray B. Urowitz, Juanita Romero‐Diaz, Caroline Gordon, Sang‐Cheol Bae, Sasha Bernatsky, Ann E. Clarke, Daniel J. Wallace, Joan T. Merrill, David A. Isenberg, Anisur Rahman, Ellen M. Ginzler, Michelle Petri, Ian N. Bruce, M. A. Dooley, Paul Fortin, Dafna D. Gladman, Jorge Sanchez‐Guerrero, Kristjan Steinsson, Rosalind Ramsey‐Goldman, Munther A. Khamashta, Cynthia Aranow, Graciela S. Alarcón, Barri J. Fessler, Susan Manzi, Ola Nived, Gunnar K. Sturfelt, Asad A. Zoma, Ronald F. van Vollenhoven, Manuel Ramos‐Casals, Guillermo Ruiz‐Irastorza, S. Sam Lim, Kenneth C. Kalunian, Murat Inanc, Diane L. Kamen, Christine A. Peschken, Soren Jacobsen, Anca Askanase, Chris Theriault, Vernon Farewell
Journal: Arthritis & Rheumatology (2016)

To study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach.Patients in the Systemic Lupus International Collaborating Clinics inception cohort were classified annually into estimated GFR state 1 (>60 ml/minute), state 2 (30-60 ml/minute), or state 3 (<30 ml/minute) and estimated proteinuria state 1 (<0.25 gm/day), state 2 (0.25-3.0 gm/day), or state 3 (>3.0 gm/day), or end-stage renal disease (ESRD) or death. Using multistate modeling, relative transition rates between states indicated improvement and deterioration.Of 1,826 lupus patients, 700 (38.3%) developed LN. During a mean ± SD follow-up of 5.2 ± 3.5 years, the likelihood of improvement in estimated GFR and estimated proteinuria was greater than the likelihood of deterioration. After 5 years, 62% of patients initially in estimated GFR state 3 and 11% of patients initially in estimated proteinuria state 3 transitioned to ESRD. The probability of remaining in the initial states 1, 2, and 3 was 85%, 11%, and 3%, respectively, for estimated GFR and 62%, 29%, and 4%, respectively, for estimated proteinuria. Male sex predicted improvement in estimated GFR states; older age, race/ethnicity, higher estimated proteinuria state, and higher renal biopsy chronicity scores predicted deterioration. For estimated proteinuria, race/ethnicity, earlier calendar years, damage scores without renal variables, and higher renal biopsy chronicity scores predicted deterioration; male sex, presence of lupus anticoagulant, class V nephritis, and mycophenolic acid use predicted less improvement.In LN, the expected improvement or deterioration in renal outcomes can be estimated by multistate modeling and is preceded by identifiable risk factors. New therapeutic interventions for LN should meet or exceed these expectations.