tbuckley/cabot-search huggingface dataset:
Intramolecular hydrogen bonding: An opportunity for improved design in medicinal chemistry
Authors: Giulia Caron, Jan Kihlberg, Giuseppe Ermondi
Journal: Medicinal Research Reviews (2019)

Recent literature shows that intramolecular hydrogen bond (IMHB) formation can positively impact upon the triad of permeability, solubility, and potency of drugs and candidates. IMHB modulation can be applied to compounds in any chemical space as a means for discovering drug candidates with both acceptable potency and absorption, distribution, metabolism, and excretion-Tox profiles. Integrating IMHB formation in design of drugs is, therefore, an exciting and timely challenge for modern medicinal chemistry. In this review, we first provide some background about IMHBs from the medicinal chemist's point of view and highlight some IMHB-associated misconceptions. Second, we propose a classification of IMHBs for drug discovery purposes, review the most common in silico tactics to include IMHBs in lead optimization and list some experimental physicochemical descriptors, which quantify the propensity of compounds to form IMHBs. By focusing on the compounds size and the number of IMHBs that can potentially be formed, we also outline the major difficulties encountered when designing compounds based on the inclusion of IMHBs. Finally, we discuss recent case studies illustrating the application of IMHB to optimize cell permeability and physicochemical properties of small molecules, cyclic peptides and macrocycles.
Abstract 12244: 48 Week Outcomes Using Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Pulmonary Vein Stenosis
Authors: Kara Western, Mark Kieran, Christopher Baird, Christina Ireland, Steven D Colan, Kimberlee Gauvreau, Audrey C Marshall, Laureen Sena, Kathy J Jenkins
Journal: Circulation (2014)

Introduction: Intraluminal pulmonary vein stenosis (PVS) can occur in isolation, with congenital heart disease (CHD), chronic lung disease, or both. PVS can progress rapidly with vessel atresia, pulmonary hypertension, and RV failure, and can be fatal within months (mos) of diagnosis. Previous research has demonstrated that intraluminal obstruction occurs due to neointimal proliferation of myofibroblast-like cells, which express VEGF and PDGFR. Hypothesis: Adjunct targeted inhibition of VEGF (bevacizumab) and PDGFR (imatinib mesylate) may reduce disease activity in patients (pts) with multivessel intraluminal PVS and prolong survival. Methods: This is a single-arm, prospective, open-label FDA approved study using bevacizumab and imatinib mesylate to treat progressive multivessel intraluminal PVS. Pts with obstruction of ≥ 2 veins (echocardiographic (Echo) mean gradient ≥ 4 mmHg) were included after aggressive surgical or catheter based relief of obstruction. All but 3 pts had ≥ 1 PVS surgery prior to initiation. Pts with CHD received imatinib mesylate only, those without CHD or who progressed on study also received bevacizumab. Follow-up included lung scan and Echo q 4-8 weeks (wks); CT scan or angiography q 24 wks. We report initial (31 of 44 enrolled pts) who have reached 48 wks or study endpoint. Results: Among 31 pts, 17 were treated for 48 wks; 3 transplanted; 11 discontinued drug &lt; 48 wks. Mean age at diagnosis was 4 mos; drug initiation 9 mos. Two had isolated disease, 16 CHD, 3 lung disease, 10 both. Twenty-four pts received imatinib mesylate only; 7 both drugs. Median number of pulmonary veins involved was 4 (range 2-5); 12 pts had ≥ 1 atretic vessel at initiation. Pts received mean of 85% planned doses of drug. At 48 wks, 26/31 (84%) were alive, 2 post-transplant. Eight of 31 (26%) stabilized, 6/31 (19%) did not require any subsequent pulmonary vein intervention. Conclusions: Multi-modal treatment including aggressive surgical and catheter based intervention and targeted inhibition of myofibroblast proliferation resulted in a 48 wk survival of 84% among pts with multivessel intraluminal PVS. These results suggest that targeted inhibition may play an important role in managing aggressive pulmonary vein disease.
AB0356 Building a patient-centred cardiovascular risk reduction program for patients with inflammatory arthritis
Authors: I.Y. Navarro-Millan, S. Young, S. Shurbaji, C. McDavid, A. Cornelius-Schecter, B. Johnson, A. Cherrington, L. Fraenkel, J. Curtis, M. Safford
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Cardiovascular disease (CVD) is the most common cause of death among patients with inflammatory arthritis (IA) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS). <h3>Objectives</h3> This study is the formative work to help design a patient-centred intervention for a CVD risk reduction program for patients with IA. <h3>Methods</h3> We conducted a qualitative study guided by Bandura's Social Cognitive Theory, placing special focus on knowledge about the relationship between arthritis and CVD as well as barriers and facilitators to receiving healthcare related to CVD risk such as screening and management for hyperlipidemia. Participants had to have either RA, PsA or AS and were recruited from a single academic centre. Data were analysed thematically. <h3>Results</h3> We conducted three focus groups with a total of 17 participants. Mean age of participants was 56 (SD ±7.7) years; 15 were women; 3 were on a statin; and 1 previously had a stroke. The majority of the participants were Five themes emerged: 1) Need for more information about IA and medications; 2) Lack of education about CVD risk and IA; 3) CVD risk reduction as an integrated lifestyle modification; 4) Uses for peer support around relevant CVD risk factor mitigation approaches; and 5) Improving doctor-patient communication about RA. The themes that emerged in our study showed that the majority of these IA patients were not aware of the relationship between CVD and IA, and were very interested in learning about IA, medication side effects, and prognosis of IA. These participants wanted to learn first about IA and, as a secondary goal, learn about their CVD risk in the context of their IA rather than as a new condition. <h3>Conclusions</h3> Providing a clear understanding about systemic effects of IA and how to treat it will be needed before focusing on CVD risk reduction. By doing so, there will be better opportunity for the CVD risk reduction program to succeed. <h3>Disclosure of Interest</h3> I. Navarro-Millan: None declared, S. Young: None declared, S. Shurbaji: None declared, C. McDavid: None declared, A. Cornelius-Schecter: None declared, B. Johnson: None declared, A. Cherrington Grant/research support from: Boehringer Ingleheim, Consultant for: Novo Nordisk, Astra Zeneca, L. Fraenkel: None declared, J. Curtis: None declared, M. Safford Grant/research support from: Amgen, Inc
AB1093 Can dmards therapy modify clinical history of oligoarticular juvenile idiopathic arthritis (JIA)?
Authors: E. Bertoldo, C. Mansoldo, F. Martinis, G. Dallagiacoma, D. Biasi, M. Rossini, S. Pieropan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Therapy of oligoarticular JIA is based on intrarticular injections of steroids, methotrexate and biotechnological therapy. ANAs-positive oligoarticular JIA patients with an early onset of disease have a consistent risk to develop uveites. <h3>Objectives</h3> The primary aim of this study is to evaluate longitudinally the effect of non-systemic therapy and of systemic immmunomodulating drugs (e.g MTX) on ANAs in JIA patients; secondary occurance of iridocyclitis was evaluated. <h3>Methods</h3> Monocentric retrospective not randomised study of 40 patients affected by oligoarticular JIA (ILAR classification) with ANA positivity at the baseline (T0, time of diagnosis). Patient of Group 1 received only intra-articular infiltrations or NSAID. Patients of Group 2 were treated with DMARDs (most of them with subcutaneous MTX 15 mg/m2/week) or MTX +biotechnlogical therapies. The assay for ANAs (I.I.F.) was assessed in all patients at T0, at T1 (12 months) and T2 (24 months). At 24 months was also recorded the occurence of uveitis during the follow up. Exclusion criteria were the ANAs negativity at T0 and other subgroups of JIA. <h3>Results</h3> Twenty-one patients (52,5%) were treated with non-systemic therapy (Group 1), and ninenteen (47,5%) with systemic immunomodulating therapy (Group 2). In Group 2 fifteen subjects were treated with MTX, one with MTX plus cyclosporine, one with only cyclosporine, two with MTX plus biotechnological agent (etarnecept and adalimumab). At T1, in Group 1 only one patient out of 20 (4,8%) became ANAs negative versus 42,1% (8/19) of patients in Group 2 (p 0.0033). At T2 the incidence of ANAs positivity did not change in Group 1 (only 1/21 ANAs negative), while 42,1% of patients treated with systemic therapies were ANA negative (p 0.006). Three patients were lost at the follow up. The two patients who received bDMARDs in addition to MTX remained ANAs-positive both in T1 and T2. At the end of follow-up period eight uveitis have occured, six in ANAs positive patients of Group 1 (6/21, 28,5%) and two in ANA negatives patients in Group 2 (2/19, 10,5%). <h3>Conclusions</h3> ANAs-positive patients treated with methotrexate seems to have higher possibility to became ANAs-negative versus patients treated with non-systemic immunomodulating therapy. It's known that MTX might prevent onset of uveitis in JIA, as shown in our results. Demostrating a negativization of antinuclear antibodies using MTX therapy could help to add a role of this drug in the disease history of the oligoarthritis. <h3>Disclosure of Interest</h3> None declared
Optimized Arylomycins May Help Address Antibiotic Resistance
Authors: Tracy Hampton
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 19509: Palliative Care and Hospital Readmissions in Patients With Advanced Heart Failure: Insights From the PAL-HF Trial
Authors: Robert J Mentz, Bradi B Granger, Hongqiu Yang, Kevin J Anstrom, Christopher M O’Connor, Chetan B Patel, Mona Fuzat, Gwen Dodson, Patricia Adams, James A Tulsky, joseph G Rogers
Journal: Circulation (2016)

Background: The PAL-HF trial intervention improved quality of life (QOL) compared to usual care in advanced heart failure (HF) patients. Patients with end-stage HF have a significant symptom burden...
Reproducing indolent B-cell lymphoma transformation with T-cell immunosuppression in LMP1/CD40-expressing mice
Authors: Christelle Vincent-Fabert, Alexis Saintamand, Amandine David, Mehdi Alizadeh, François Boyer, Nicolas Arnaud, Ursula Zimber-Strobl, Jean Feuillard, Nathalie Faumont
Journal: Cellular and Molecular Immunology (2019)

Transformation of an indolent B-cell lymphoma is associated with a more aggressive clinical course and poor survival. The role of immune surveillance in the transformation of a B-cell indolent lymphoma towards a more aggressive form is poorly documented. To experimentally address this question, we used the L.CD40 mouse model, which is characterized by B-cell specific continuous CD40 signaling, responsible for spleen indolent clonal or oligoclonal B-cell lymphoma after one year in 60% cases. Immunosuppression was obtained either by T/NK cell depletion or by treatment with the T-cell immunosuppressive drug cyclosporin A. Immunosuppressed L.CD40 mice had larger splenomegaly with increased numbers of B-cells in both spleen and peripheral blood. High-throughput sequencing of immunoglobulin variable segments revealed that clonal expansion was increased in immunosuppressed L.CD40 mice. Tumor B cells of immunosuppressed mice were larger with an immunoblastic aspect, both on blood smears and spleen tissue sections, with increased proliferation rate and increased numbers of activated B-cells. Collectively, these features suggest that immune suppression induced a shift from indolent lymphomas into aggressive ones. Thus, as a preclinical model, immunosuppressed L.CD40 mice reproduce aggressive transformation of an indolent B-cell tumor and highlight the role of the immune surveillance in its clinical course, opening new perspective for immune restoration therapies.
Cost-Effectiveness of Blinatumomab Versus Standard of Care in Adult Patients with Philadelphia-Chromosome-Negative B-Precursor Acute Lymphoblastic Leukemia in First Hematological Complete Remission (CR) with Minimal Residual Disease (MRD) from a US Payer Perspective
Authors: Thomas Delea, Nicholas Despiegel, Diana Boyko, Jordan Amdahl, Ze Cong, Jerald Radich
Journal: Blood (2018)
Abstract 21156: Abo Status and Stroke Free Survival in Lvad Patients
Authors: Onyedika J Ilonze, David Sane, Stephen G Phillips, Katherine Shaver
Journal: Circulation (2017)

Introduction: Left Ventricular Assist Devices (LVAD) improve survival in selected patients. Complications include thromboembolism and bleeding. Alterations in von Willebrand factor (vWF) multimers may play a role, especially with continuous flow LVADs. AbO antigens are expressed on vWF where these antigens influence its processing into subunits. There are reports of higher bleeding rates in O patients and higher thrombosis rates in non-O patients. Hypothesis: ABO status is routinely determined prior to LVAD implantation and we correlated ABO status with outcomes. It may allow adjustment of anticoagulation to minimize adverse events. Methods: We studied adults with first implant of continuous axial LVAD entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). The implant operations occurred between the second quarters of 2012-2016. A total pf 6,462 patients were studied. A Cox proportional hazards model was analyzed using gender, age category, BMI, white race and blood type to predict the hazard rate of stroke or death after implant. Follow up was from time of implant until death, transplant, exchange, recovery, stroke or end of data set. Results: Increases in the hazard rate was seen in females (HR 1,26, 95% CI: 1.13-1.41; p&lt;0.0001); age &gt;50 (HR 1.62; 95% CI 1.42- 1.84; p&lt;0.0001), and white race (HR 1.18; 95% CI: 1.06-1.31; p=0.002). Blood group O decreased the hazard rate compared to patients with non-O blood group (HR 0.92; 95% CI: 0.83-1.00; p=0.06). Conclusions: O blood group was associated with improved stroke free survival in multivariate analysis including gender, age category, BMI and race. This effect could be due to the lower levels of vWF in O blood group patients. Further work is being done to assess the effect of ABO blood group status on other thromboembolic events as well as bleeding outcomes. The impact of antiplatelet agents and anticoagulants on these outcomes will also need to be evaluated.
Abstract P168: Evaluation of the American Heart Association’s “Check Change ControlTM”- Blood Pressure Control Program
Authors: Rohini J Patel, Chirag Desai, Cevadne Lee, Sang-Mi Oh, Nathan D Wong
Journal: Circulation (2016)

Background: Blood pressure (BP) awareness, treatment and control remains suboptimal among US adults with hypertension. In response, the AHA has developed the “Check. Change. Control. TM” (CCC) BP program to reduce BP in those with elevated BP. We evaluated the efficacy of this program as implemented in a sample of Asian and Hispanic senior citizens in Southern California. Methods: We studied 122 participants aged &gt;62 years (93% Chinese and 7% Hispanic) who participated in the CCC program in Los Angeles and Orange Counties, California. Systolic (SBP) and diastolic blood pressure (DBP) was recorded over the CCC program resulting in 8 readings over 4 months during which participants learned self-monitoring, tracking BP, the use of the Heart360 TM digital tool, and self-management skills. Participants in this analysis were required to have baseline, final, and at least two interim BP measures. BP changes from baseline to mid-study and final visit were examined by the paired t-test among the whole cohort and in those with elevated BP (&gt;=140 SBP and/or &gt;=90 DBP) at baseline. Results: Average baseline SBP was 136.8 (19.4) mm Hg and DBP was 76.0 (12.0) mm Hg. At baseline, 46.7% of the participants had elevated BP, which was reduced to 41% by the final visit. The figure depicts the change in SBP and DBP from baseline to mid visit and final visit for the overall cohort and those with elevated BP at baseline. There were significant reductions in both SBP and DBP overall and especially among those with elevated BP at baseline. Further, 36.1% of participants had a SBP drop of &gt;10 mm Hg from baseline to final visit. Conclusion: In conclusion, the AHA’s CCC program had a significant impact in reducing BP in our AHA CCC participants, especially among those with elevated BP at baseline. Further study should investigate the specific program and patient factors that best predict blood pressure reduction.
AB0166 Tracking of mucocutanous and musculoskeletal flares in sle using serum fas, ferritin, igfbp2 and stnfrii
Authors: S. Soliman, K. Vanarsa, A. Swilling, J. Merrill, C. Mohan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> SLE is a multisystemic autoimmune disease characterized by unpredictable disease course with periods of flares and remission. The lack of reliable methods which can predict a disease flare hampers the exploration of effective and preventive strategies for disease relapses. <h3>Objectives</h3> To study the performance of serum FAS, sTNFRII, Igfbp2 and Ferritin as biomarkers for tracking lupus flares in non-renal SLE patients. <h3>Methods</h3> Twenty-nine patients, who met the requirements of American College of Rheumatology (ACR) for classification of SLE, were recruited from Oklahoma Medical Research Foundation (OMRF) for serological testing of all four serum protein markers. None of the patients had lupus nephritis. Serum samples were obtained over 4 consecutive visits. Serum FAS, sTNFRII, Igfbp2 and Ferritin molecules were measured in all patients. Lupus disease activity was assessed by both SLEDAI and BILAG activity indices. <h3>Results</h3> In our study, all 4 tested biomarkers (FAS, Ferritin, Igfbp2 and sTNFRII) showed significant correlations with SLEDAI and BILAG. FAS (r= 0.36, p&lt;0.0001 for SLEDAI &amp; r= 0.29, p= 0.0002 for BILAG), Ferritin (r= 0.13, p=0.0494 for SLEDAI &amp; r= 0.22, p= 0.0035 for BILAG), Igfbp2 (r= 0.24, p= 0.0013 for SLEDAI &amp; r= 0.18, p= 0.0106 for BILAG) and sTNFRII (r= 0.30, p&lt;0.0001 for SLEDAI &amp; r= 0.19, p= 0.0112 for BILAG). When serial disease activity changes were examined, different serum markers performed better in different SLE patients, tracking with mucocutaneous or musculoskeletal disease flares. In studying a total of 72 disease intervals, FAS and Ferritin exhibited the highest concordance with concurrent disease activity (58–62%), followed by Igfbp2 (50%) and sTNFRII (46%), all of which were superior to the performance of complement C3, C4 and anti-DNA. Furthermore, adding FAS to other tested molecules increased its ability to track concordant disease activity changes (81% for FAS±Ferritin; 76% for FAS±Igfbp2 and FAS±sTNFRII). <h3>Conclusions</h3> Serum FAS and Ferritin emerge as potential serum markers for tracking mucocutaneous or musculoskeletal disease flares in SLE patients. <h3>Disclosure of Interest</h3> None declared
Expression Signature of Myeloma Residual Cells Is Characterized By Genes Associated with Proliferation, Epigenetic Modification, and Stem Cell Maintenance
Authors: Michael A Bauer, Matthew Henry, Purvi Patel, Yan Wang, Joshua Epstein, Faith E. Davies, Carolina D. Schinke, Maurizio Zangari, Sharmilan Thanendrarajan, Frits van Rhee, Gareth Morgan, Brian A Walker, Sarah K Johnson
Journal: Blood (2018)
A Fussy Infant With a Generalized Papulovesicular Rash
Authors: Ge Qian, Ligong Hou, Wu Guo
Journal: JAMA (2019)

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