tbuckley/cabot-search huggingface dataset:
Risk Assessment after Neoadjuvant Chemotherapy in Luminal Breast Cancer Using a Clinicomolecular Predictor
Authors: Sibylle Loibl, Karsten Weber, Jens Huober, Kristin Krappmann, Frederik Marmé, Christian Schem, Knut Engels, Berit Maria Pfitzner, Sherko Kümmel, Jenny Furlanetto, Arndt Hartmann, Silvia Darb-Esfahani, Volkmar Müller, Annette Staebler, Gunter von Minckwitz, Ralf Kronenwett, Carsten Denkert
Journal: Clinical Cancer Research (2018)

Purpose: This study aimed to evaluate a modified EPclin test (mEPclin), a combination of EndoPredict (EP) score, post-neoadjuvant pathologic tumor size and nodal status, for predicting the risk of distance recurrence after neoadjuvant chemotherapy (NACT) in patients with residual estrogen receptor (ER)-positive/HER2-negative breast cancer. We also compared the prognostic power of the mEPclin with that of the CPS-EG score.Experimental Design: A total of 428 formalin-fixed, paraffin-embedded tumor samples from GeparTrio and GeparQuattro studies were evaluated for mRNA expression of eight cancer-related and three reference genes. The mEPclin score was computed using a modified algorithm and predefined cut-off values were used to classify each patient at low or high risk. Primary endpoint was disease-free survival (DFS).Results: A higher continuous mEPclin score was significantly associated with increased risk of relapse [HR, 2.16; 95% confidence interval (CI), 1.86-2.51; P < 0.001] and death (HR, 2.28; 95% CI, 1.90-2.75; P < 0.001). Similarly, patients classified at high risk by dichotomous mEPclin showed significantly poorer DFS and overall survival compared with those at low risk. In contrast with CPS-EG, the mEPclin remained significantly prognostic for DFS in multivariate analysis (HR, 2.13; 95% CI, 1.73-2.63; P < 0.001). Combining CPS-EG and other clinicopathological variables with mEPclin yielded a significant improvement of the prognostic power for DFS versus without mEPclin (c-indices: 0.748 vs. 0.660; P < 0.001).Conclusions: The mEPclin score independently predicted the risk of distance recurrence and provided additional prognostic information to the CPS-EG score to assess more accurately the prognosis after NACT in the luminal non-pCR patient population. Therefore, this approach can be used to select patients for additional post-neoadjuvant therapies. Clin Cancer Res; 24(14); 3358-65. ©2018 AACR.
Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway
Authors: Rosemarie Tremblay-LeMay, Nasrin Rastgoo, Hong Chang
Journal: Journal of Hematology & Oncology (2018)

Even with recent advances in therapy regimen, multiple myeloma patients commonly develop drug resistance and relapse. The relevance of targeting the PD-1/PD-L1 axis has been demonstrated in pre-clinical models. Monotherapy with PD-1 inhibitors produced disappointing results, but combinations with other drugs used in the treatment of multiple myeloma seemed promising, and clinical trials are ongoing. However, there have recently been concerns about the safety of PD-1 and PD-L1 inhibitors combined with immunomodulators in the treatment of multiple myeloma, and several trials have been suspended. There is therefore a need for alternative combinations of drugs or different approaches to target this pathway. Protein expression of PD-L1 on cancer cells, including in multiple myeloma, has been associated with intrinsic aggressive features independent of immune evasion mechanisms, thereby providing a rationale for the adoption of new strategies directly targeting PD-L1 protein expression. Drugs modulating the transcriptional and post-transcriptional regulation of PD-L1 could represent new therapeutic strategies for the treatment of multiple myeloma, help potentiate the action of other drugs or be combined to PD-1/PD-L1 inhibitors in order to avoid the potentially problematic combination with immunomodulators. This review will focus on the pathophysiology of PD-L1 expression in multiple myeloma and drugs that have been shown to modulate this expression.
What Patients Expect and Deserve
Authors: Carol Elizabeth Gunn
Journal: JAMA Internal Medicine (2018)

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
Identifying early pulmonary arterial hypertension in patients with systemic sclerosis
Authors: Robin Condliffe, Gabor Kovacs
Journal: European Respiratory Journal (2018)

Pulmonary arterial hypertension (PAH) is a life-shortening complication of systemic sclerosis (SSc) with a life-time prevalence of approximately 10% [1, 2]. It is currently defined by the presence of a mean pulmonary arterial pressure (mPAP) ≥25 mmHg with a pulmonary arterial wedge pressure (PAWP) ≤15 mmHg and a pulmonary vascular resistance (PVR) >3 WU, in the absence of significant lung disease or chronic thromboembolic disease. Other forms of pulmonary hypertension (PH) may also quite commonly exist in SSc patients, including PH due to left heart disease or lung disease. It is widely agreed that identifying patients with SSc who also have PAH (SSc-PAH) earlier in their disease process is likely a good idea with the presumption that earlier diagnosis leads to earlier treatment, which hopefully leads to better outcomes. Certainly, previous data have demonstrated superior survival in patients with SSc-PAH identified by screening when compared with patients presenting due to symptoms [3]. Over the past few years several groups have investigated the optimal way of screening SSc patients for the presence of PAH, most notably the DETECT investigators [4]. The DETECT study demonstrated that in a population of SSc patients enriched for the likely presence of PAH (by including patients only with a diffusion coefficient for carbon monoxide, D LCO, <60% predicted), a two-step algorithm including electrocardiographic, echocardiographic and laboratory biomarkers selecting patients to undergo right heart catheterisation (RHC) had greater sensitivity than echocardiography alone in identifying patients with PH. Superiority in clinical practice in non-enriched populations of SSc patients when compared to approaches combining echocardiography, trends in D LCO and clinical history has not been clearly demonstrated [5]. Nevertheless, the DETECT algorithm has been a welcome introduction in stimulating efforts to identify SSc-PAH patients at an earlier stage. New data to help earlier identification of patients with pulmonary arterial hypertension associated with systemic sclerosis [ http://ow.ly/lwsC30j2055][1] [1]: http://ow.ly/lwsC30j2055
Advanced machine learning in action: identification of intracranial hemorrhage on computed tomography scans of the head with clinical workflow integration
Authors: Mohammad R. Arbabshirani, Brandon K. Fornwalt, Gino J. Mongelluzzo, Jonathan D. Suever, Brandon D. Geise, Aalpen A. Patel, Gregory J. Moore
Journal: npj Digital Medicine (2018)

Intracranial hemorrhage (ICH) requires prompt diagnosis to optimize patient outcomes. We hypothesized that machine learning algorithms could automatically analyze computed tomography (CT) of the head, prioritize radiology worklists and reduce time to diagnosis of ICH. 46,583 head CTs (~2 million images) acquired from 2007-2017 were collected from several facilities across Geisinger. A deep convolutional neural network was trained on 37,074 studies and subsequently evaluated on 9499 unseen studies. The predictive model was implemented prospectively for 3 months to re-prioritize "routine" head CT studies as "stat" on realtime radiology worklists if an ICH was detected. Time to diagnosis was compared between the re-prioritized "stat" and "routine" studies. A neuroradiologist blinded to the study reviewed false positive studies to determine whether the dictating radiologist overlooked ICH. The model achieved an area under the ROC curve of 0.846 (0.837-0.856). During implementation, 94 of 347 "routine" studies were re-prioritized to "stat", and 60/94 had ICH identified by the radiologist. Five new cases of ICH were identified, and median time to diagnosis was significantly reduced (p < 0.0001) from 512 to 19 min. In particular, one outpatient with vague symptoms on anti-coagulation was found to have an ICH which was treated promptly with reversal of anticoagulation, resulting in a good clinical outcome. Of the 34 false positives, the blinded over-reader identified four probable ICH cases overlooked in original interpretation. In conclusion, an artificial intelligence algorithm can prioritize radiology worklists to reduce time to diagnosis of new outpatient ICH by 96% and may also identify subtle ICH overlooked by radiologists. This demonstrates the positive impact of advanced machine learning in radiology workflow optimization.
Mechanistic Insights of an Immunological Adverse Event Induced by an Anti-KIT Antibody Drug Conjugate and Mitigation Strategies
Authors: Lawrence L'Italien, Olivia Orozco, Tinya Abrams, Lisa Cantagallo, Anu Connor, Jayesh Desai, Hilmar Ebersbach, Hans Gelderblom, Keith Hoffmaster, Emma Lees, Heiko Maacke, Siew Schleyer, Darko Skegro, Si Tuen Lee-Hoeflich
Journal: Clinical Cancer Research (2018)

Purpose: Hypersensitivity reactions (HSRs) were observed in three patients dosed in a phase I clinical trial treated with LOP628, a KIT targeted antibody drug conjugate. Mast cell degranulation was implicated as the root cause for the HSR. Underlying mechanism of this reported HSR was investigated with an aim to identifying potential mitigation strategies.Experimental Design: Biomarkers for mast cell degranulation were evaluated in patient samples and in human peripheral blood cell-derived mast cell (PBC-MC) cultures treated with LOP628. Mitigation strategies interrogated include pretreatment of mast cells with small molecule inhibitors that target KIT or signaling pathways downstream of FcεR1, FcγR, and treatment with Fc silencing antibody formats.Results: Transient elevation of serum tryptase was observed in patients 1-hour posttreatment of LOP628. In agreement with the clinical observation, LOP628 and its parental antibody LMJ729 induced degranulation of human PBC-MCs. Unexpectedly, KIT small molecule inhibitors did not abrogate mast cell degranulation. By contrast, small molecule inhibitors that targeted pathways downstream of Fc receptors blunted degranulation. Furthermore, interference of the KIT antibody to engage Fc receptors by pre-incubation with IgG or using engineered Fc silencing mutations reduced or prevented degranulation. Characterization of Fcγ receptors revealed human PBC-MCs expressed both FcγRII and low levels of FcγRI. Interestingly, increasing the level of FcγRI upon addition of IFNγ, significantly enhanced LOP628-mediated mast cell degranulation.Conclusions: Our data suggest LOP628-mediated mast cell degranulation is the likely cause of HSR observed in the clinic due to co-engagement of the FcγR and KIT, resulting in mast cell activation. Clin Cancer Res; 24(14); 3465-74. ©2018 AACR.
Glyphosate Levels in Older Adults—Reply
Authors: Paul J. Mills, Linda K. McEvoy, Gail A. Laughlin
Journal: JAMA (2018)

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
Clinical implication of nutrition for neoadjuvant therapy and impact of nutritional support in pancreatic cancer.
Authors: Mitsuru Tashiro, Suguru Yamada, Tsutomu Fujii, Norifumi Hattori, Hideki Takami, Masaya Suenaga, Yukiko Niwa, Masamichi Hayashi, Naoki Iwata, Mitsuro Kanda, Chie Tanaka, Daisuke Kobayashi, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2018)

416 Background: Several studies have shown that nutritional support is important to reduce chemotherapy-related toxicities and improve tolerance to chemotherapy, but little is known about the nutritional influence of neoadjuvant therapy (NAT) for pancreatic cancer. The aim of this study was to assess the influence of NAT on nutritional status and the effectiveness of postoperative nutritional support in patients with NAT for pancreatic cancer. Methods: Between 2010 and 2017, 169 consecutive patients who underwent pancreatoduodenectomy of pancreatic cancer were enrolled, and divided into the neoadjuvant group (NAG, n = 70) and the control group (CG, n = 99). We assessed the change of nutritional index (body weight, albumin and rapid turnover proteins; retinol binding protein, prealbumin and transferrin), inflammatory index, and inflammation-based prognostic scores during NAT. Perioperative change of rapid turnover proteins at the point of pre-operation, postoperative day (POD) 5, POD12 and POD21, and perioperative and oncological outcomes between NAG and CG were evaluated. Finally, we divided NAG into nutrition group (n = 27) who received postoperative enteral immunonutrition from POD 1 to POD 21 and without nutrition group (n = 41), and compared perioperative change of rapid turnover proteins between two groups. Results: After NAT, the retinol binding protein, prealbumin, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and prognostic nutrition index significantly got worse in NAG (P &lt; 0.05). The recovery of rapid turnover proteins after POD5 was significantly worse in NAG compared to CG (P &lt; 0.05). There was no significant difference in the incidence of postoperative complications and time to adjuvant therapy between two groups. The recovery of retinol binding protein and prealbumin after POD12 was significantly better in nutrition group compared to without nutrition group (P &lt; 0.05). Conclusions: NAT for pancreatic cancer could decrease nutritional status and its postoperative recovery. Postoperative enteral nutrition could be effective in patients with NAT for pancreatic cancer. Based on these results, we plan to perform the nutritional support at earlier stage of therapy.
The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial
Authors: Thomas A Rasmussen, James H McMahon, J Judy Chang, Jennifer Audsley, Ajantha Rhodes, Surekha Tennakoon, Ashanti Dantanarayana, Tim Spelman, Tina Schmidt, Stephen J Kent, Vincent Morcilla, Sarah Palmer, Julian H Elliott, Sharon R Lewin
Journal: The Lancet HIV (2018)
Estimating the numbers of pregnant women infected with Zika virus and infants with congenital microcephaly in Colombia, 2015–2017
Authors: Alys Adamski, Jeanne Bertolli, Carlos Castañeda-Orjuela, Owen J. Devine, Michael A. Johansson, Maritza Adegnis Gonzalez Duarte, Sherry L. Farr, Sarah C. Tinker, Marcela Maria Mercado Reyes, Van T. Tong, Oscar Eduardo Pacheco Garcia, Diana Valencia, Diego Alberto Cuellar Ortiz, Margaret A. Honein, Denise J. Jamieson, Martha Lucía Ospina Martínez, Suzanne M. Gilboa
Journal: Journal of Infection (2018)
Practical Guide to Surgical Data Sets: Healthcare Cost and Utilization Project National Inpatient Sample (NIS)
Authors: Jonah J. Stulberg, Elliott R. Haut
Journal: JAMA Surgery (2018)

This Guide to Statistics and Methods summarizes the key characteristics, strengths, and limitations of the National Inpatient Sample, a data set within AHRQ's Healthcare Cost and Utilization Project data set collection, for use in surgical health services research.
Lessons from the Crypt: HMGA1—Amping up Wnt for Stem Cells and Tumor Progression
Authors: Linda Resar, Lionel Chia, Lingling Xian
Journal: Cancer Research (2018)

High mobility group A1 (HMGA1) chromatin remodeling proteins are enriched in aggressive cancers and stem cells, although their common function in these settings has remained elusive until now. Recent work in murine intestinal stem cells (ISC) revealed a novel role for Hmga1 in enhancing self-renewal by amplifying Wnt signaling, both by inducing genes expressing Wnt agonist receptors and Wnt effectors. Surprisingly, Hmga1 also "builds" a stem cell niche by upregulating Sox9, a factor required for differentiation to Paneth cells; these cells constitute an epithelial niche by secreting Wnt and other factors to support ISCs. HMGA1 is also highly upregulated in colon cancer compared with nonmalignant epithelium and SOX9 becomes overexpressed during colon carcinogenesis. Intriguingly, HMGA1 is overexpressed in diverse cancers with poor outcomes, where it regulates developmental genes. Similarly, HMGA1 induces genes responsible for pluripotency and self-renewal in embryonic stem cells. These findings demonstrate that HMGA1 maintains Wnt and other developmental transcriptional networks and suggest that HMGA1 overexpression fosters carcinogenesis and tumor progression through dysregulation of these pathways. Studies are now needed to determine more precisely how HMGA1 modulates chromatin structure to amplify developmental genes and how to disrupt this process in cancer therapy. Cancer Res; 78(8); 1890-7. ©2018 AACR.
Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study
Authors: Kenneth G Saag, Rachel B Wagman, Piet Geusens, Jonathan D Adachi, Osvaldo D Messina, Ronald Emkey, Roland Chapurlat, Andrea Wang, Nicola Pannacciulli, Willem F Lems
Journal: The Lancet Diabetes & Endocrinology (2018)
Building capacity for global mental health research: challenges to balancing clinical and research training
Authors: Maria A Oquendo, Cristiane Duarte, Lidia Gouveia, Jair J Mari, Marcelo F Mello, Carolyn M Audet, Ilana Pinsky, Sten H Vermund, Ana O Mocumbi, Milton L Wainberg
Journal: The Lancet Psychiatry (2018)
Lower Cancer Incidence—Warfarin Effect or Immortal Time Bias?
Authors: Xiaojuan Li, Jennifer L. Lund, Sengwee Toh
Journal: JAMA Internal Medicine (2018)

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
Responsibility: Cognitive fragments and collaborative coherence?
Authors: James S. Uleman, Yael Granot, Yuki Shimizu
Journal: Behavioral and Brain Sciences (2018)

Abstract We describe additional research that expands upon many of Doris's points, focusing on collaboration (Ch. 5), selves, and identity (Ch. 8). We also suggest some elaboration of his treatment of dual process theories (Ch. 3). Finally, we ask whether collaborationist accounts confer logical consistency.
Gadofosveset-enhanced lung magnetic resonance imaging to detect ongoing vascular leak in pulmonary fibrosis
Authors: Sydney B. Montesi, Rohan Rao, Lloyd L. Liang, Hannah E. Goulart, Amita Sharma, Subba R. Digumarthy, Barry S. Shea, Ravi T. Seethamraju, Peter Caravan, Andrew M. Tager
Journal: European Respiratory Journal (2018)

Vascular leak is a cardinal response to tissue injury [1, 2]. When dysregulated, vascular leak has been shown to contribute to the development of pulmonary fibrosis in the bleomycin mouse model [3]. Specifically targeting vascular endothelial growth factor, initially described as vascular permeability factor [4] and a key mediator regulating capillary permeability, attenuates the development of pulmonary fibrosis in vivo [5]. Gadofosveset (Ablavar; Lantheus Medical Imaging Inc., North Billerica, MA, USA) is a US Food and Drug Administration-approved, gadolinium-based, albumin-binding contrast agent. Gadofosveset has been used to detect vascular permeability in mouse models [6] and to perform vascular imaging clinically. We hypothesised that gadofosveset-enhanced lung magnetic resonance imaging (MRI) could detect albumin extravasation in subjects with pulmonary fibrosis and demonstrate the location of ongoing tissue injury. Vascular leak is increased diffusely in the lungs in pulmonary fibrosis and is not limited to radiographic areas of disease involvement <http://ow.ly/Zz6Z30jb85l> We would like to gratefully acknowledge the important contributions from Mary O'Hara and Larry White of the Athinoula A. Martinos Center for Biomedical Imaging (Massachusetts General Hospital, Charlestown, MA, USA).