tbuckley/cabot-search huggingface dataset:
AT-101 or placebo (P) with docetaxel (D) in second-line NSCLC with gene signature biomarker development
Authors: N. Ready, A. Potti, N. Karaseva, S. Orlov, A. Luft, O. Popovych, P. Y. Liu, J. T. Holmlund, B. A. Wood, L. Leopold
Journal: Journal of Clinical Oncology (2009)

3577 Background: AT-101 inhibits the Bcl-2 protein family (Bcl-2, Bcl-xL, Mcl-1, Bcl-W) with broad preclinical activity including synergy with D. Methods: We conducted a randomized, double-blind, P-controlled phase 2 study. Patients had received 1 prior chemotherapy regimen for advanced NSCLC. Patients received AT-101 (40 mg b.i.d. days 1–3) or P with D (75 mg/m 2 day 1) Q 21 days. Primary endpoint was progression-free survival (PFS) by independent review (IR). Secondary endpoints were overall survival (OS) and investigator determined PFS. 102 patients were planned for 70 events (80% power, HR 0.6, 1-sided alpha 0.1). A biomarker of AT-101 activity was developed by treating 55 NSCLC cell lines with AT-101 and using the corresponding gene expression data to identify a genomic predictor of sensitivity to AT-101. Results: 106 patients were randomized. Baseline factors were balanced. Median OS for patients on AT-101+D was 7.3 months versus 5.6 months for P + D arm (HR 0.60, p = 0.05). The median investigator determined PFS was 12.6 weeks and 10.7 weeks for AT-101+D and P+D arms respectively (HR 1.0, p = 0.49); IR is ongoing. Common adverse events were fatigue (18%), anemia (18%), and dyspnea (18%). Grade 1/2 headaches occurred more frequently in the AT-101 arm. Analysis of gene expression data by Bayesian regression revealed a robust 500 gene predictor of sensitivity to AT-101 that was cross validated in a leave one out analysis and in an independent cohort of 32 NSCLC cell lines. Validation of the predictor in patient samples from the trial is ongoing. Conclusions: In this phase II trial AT-101, an oral pan Bcl-2 family inhibitor, had favorable OS compared to placebo when combined with docetaxel in previously treated NSCLC and was well tolerated. A genomic predictor of AT-101 sensitivity is likely to enrich for responders and identify novel therapeutic combinations for future [Table: see text]
Neuronal Migration on Silicon Microcone Arrays with Different Pitches
Authors: Jeongyeon Seo, Christina Lanara, Ji Yu Choi, Jungnam Kim, Hyeoncheol Cho, Young‐Tae Chang, Kyungtae Kang, Emmanuel Stratakis, Insung S. Choi
Journal: Advanced Healthcare Materials (2020)

Abstract Neuronal migration is a complicated but fundamental process for proper construction and functioning of neural circuits in the brain. Many in vivo studies have suggested the involvement of environmental physical features of a neuron in its migration, but little effort has been made for the in vitro demonstration of topography‐driven neuronal migration. This work investigates migratory behaviors of primary hippocampal neurons on a silicon microcone (SiMC) array that presents 14 different pitch domains (pitch: 2.5–7.3 µm). Neuronal migration becomes the maximum at the pitch of around 3 µm, with an upper migration threshold of about 4 µm. Immunocytochemical studies indicate that the speed and direction of migration, as well as its probability of occurrence, are correlated with the morphology of the neuron, which is dictated by the pitch and shape of underlying SiMC structures. In addition to the effects on neuronal migration, the real‐time imaging of migrating neurons on the topographical substrate reveals new in vitro modes of neuronal migration, which have not been observed on the conventional flat culture plate, but been suggested by in vivo studies.
Overcoming behavioral obstacles to prevent periodontal disease: Behavioral change techniques and self‐performed periodontal infection control
Authors: Birgitta Jönsson, Kajsa H. Abrahamsson
Journal: Periodontology 2000 (2020)

Abstract It is well established that periodontal infection control, by means of adequate oral hygiene such as daily toothbrushing and interdental cleaning, is essential for prevention of periodontal disease. Evidence suggests that oral health behavioral intervention is more effective if based on a theoretic framework that includes behavioral change techniques based on goals and planning and on feedback and monitoring. This review focuses on factors that influence behavioral changes in oral hygiene measures (both obstacles and facilitators) and a person‐centered approach to treatment planning and communication with patients. A person‐centered model of oral hygiene is presented that can be integrated into periodontal treatment using different behavioral techniques.
Moving the Financing of Graduate Medical Education Into the 21st Century
Authors: Justin A. Grischkan, Ari B. Friedman, Amitabh Chandra
Journal: JAMA (2020)

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
Covid-19 in India: Dharavi’s success story
Authors: Ashutosh Kumar, Vikas Pareek, Ravi K Narayan, Kamla Kant, Cheena Kapoor
Journal: BMJ (2020)

<h3>Abstract</h3> To guide social interaction, people often rely on expectations about the traits of other people based on markers of social group membership, i.e., stereotypes. Although the influence of stereotypes on social behavior is widespread, key questions remain about how traits inferred from social group membership are instantiated in the brain and incorporated into neural computations that guide social behavior. Here, we show that the human lateral orbitofrontal cortex (OFC) represents the content of stereotypes about members of different social groups in the service of social decision-making. During fMRI scanning, participants decided how to distribute resources across themselves and members of a variety of social groups in a modified Dictator Game. Behaviorally, we replicated our recent finding that perceptions of others’ traits, captured by a two-dimensional framework of stereotype content (warmth and competence), biased participants’ monetary allocation choices in a context-dependent manner: recipients’ warmth increased advantageous inequity aversion and their competence increased disadvantageous inequity aversion. Neurally, representational similarity analysis (RSA) revealed that perceptions of others’ traits in the two-dimensional space were represented in the temporoparietal junction and superior temporal sulcus, two regions associated with mentalizing, and in the lateral OFC, known to represent latent environmental features during goal-directed outcome inference outside the social domain. Critically, only the latter predicted individual choices, suggesting that the effect of stereotypes on behavior is mediated by inference-based, domain-general decision-making processes in the OFC.
Bioadhesive hydrogels demonstrating pH-independent and ultrafast gelation promote gastric ulcer healing in pigs
Authors: Xiayi Xu, Xianfeng Xia, Kunyu Zhang, Aliza Rai, Zhuo Li, Pengchao Zhao, Kongchang Wei, Li Zou, Boguang Yang, Wai-Ki Wong, Philip Wai-Yan Chiu, Liming Bian
Journal: Science Translational Medicine (2020)

Bioadhesive hydrogel with ultrafast gelation independent of environmental pH is endoscopically delivered to enhance gastric ulcer healing.
The evolution of IgE‐mediated type I hypersensitivity and its immunological value
Authors: David I. Pritchard, Franco H. Falcone, Piers D. Mitchell
Journal: Allergy (2020)

The allergic phenotype manifests itself in a spectrum of troublesome to life-threatening diseases, from seasonal hay fever, through the food allergies, atopic eczema, asthma, to anaphylaxis. Allergy, that is an overreaction to allergen in hypersensitive individuals, results from the production of IgE, mast cell and basophil sensitisation and degranulation, requiring a range of medications to manage the conditions. Yet it is highly likely that allergy evolved for a purpose and that allergic diseases are accidental consequences of an insufficiently regulated immune response. This article presents a viewpoint from which to restore the immunological reputation of the allergic phenotype. We consider the evolutionary origins of potential allergens, toxins and parasites, and how they might have influenced early-mammal species in existence when IgE first developed. We conclude that the allergic phenotype has likely saved the lives of many more mammals than have ever died from allergy, so justifying the positive role of IgE in our evolution.
Case of postpartum axial spondyloarthritis
Authors: Kazunori Furuhashi, Nanase Honda, Yuji Miyoshi, Naoto Yokogawa
Journal: Annals of the Rheumatic Diseases (2020)

Case of postpartum axial spondyloarthritisIn a recent issue of the Annals of Rheumatic Diseases, Hoballah et al reported high false-positive results on sacroiliac MRI based on the Assessment of SpondyloArthritis international Society (ASAS) criteria in the early postpartum period. 1 Similarly, Renson et al reported a markedly high prevalence of postpartum sacroiliac bone marrow oedema on sacroiliac MRI and recommended waiting at least 6 months after delivery to perform sacroiliac MRI. 2 Both studies excluded patients with inflammatory bowel disease.We would like to share below a case of new onset axial spondyloarthritis in an early postpartum patient with ulcerative colitis.A Japanese female patient in her 30s with ulcerative colitis in clinical remission without treatment was evaluated for a 2-month history of progressive right buttock pain which began 6 months after childbirth.Naproxen was ineffective in relieving the pain.Physical examination showed tenderness in the right sacroiliac joint and was positive for Patrick's test and Gaenslen test.Laboratory analysis showed serum C reactive protein 1.7 mg/dL and was negative for human leucocyte antigen-B27.A plain radiograph of the sacroiliac joint was normal.MRI revealed bone marrow oedema without erosion or ankylosis in the right sacroiliac joint, thus satisfying the ASAS criteria for active sacroiliitis (figure 1A).The pain dramatically improved 4 days after adalimumab treatment was begun, and the MRI findings improved by week 8 (figure 1B).In patients with inflammatory bowel disease, mechanical stress on the sacroiliac joint during labour may induce persistent inflammation leading to axial spondyloarthritis.Although the MRI findings are indistinguishable from non-specific bone marrow oedema, response to treatment can confirm the diagnosis of postpartum axial spondyloarthritis.In cases with a high index of suspicion, clinical diagnosis and prompt treatment can improve the patient's quality of life.
HMGB1 in inflammation and cancer
Authors: Shumin Wang, Yi Zhang
Journal: Journal of Hematology & Oncology (2020)

High mobility group box 1 (HMGB1) is a non-histone chromatin-associated protein widely distributed in eukaryotic cells and is involved in DNA damage repair and genomic stability maintenance. In response to stimulus like bacteria or chemoradiotherapy, HMGB1 can translocate to extracellular context as a danger alarmin, activate the immune response, and participate in the regulation of inflammation and cancer progression.
Impact of Proportionality of Secondary Mitral Regurgitation on Outcome After Transcatheter Mitral Valve Repair
Authors: Mathias Orban, Nicole Karam, Edith Lubos, Daniel Kalbacher, Daniel Braun, Simon Deseive, Michael Neuss, Christian Butter, Fabien Praz, Mohammad Kassar, Aniela Petrescu, Roman Pfister, Christos Iliadis, Matthias Unterhuber, Philipp Lurz, Holger Thiele, Stephan Baldus, Ralph Stephan von Bardeleben, Stefan Blankenberg, Steffen Massberg, Stephan Windecker, Jörg Hausleiter, Mathias Orban, Lukas Stolz, Martin Orban, Daniel Braun, Michael Näbauer, Simon Deseive, Steffen Massberg, Jörg Hausleiter, Nicole Karam, Tania Puscas, Noemie Tence, Christian Latremouille, Edith Lubos, Daniel Kalbacher, Dirk Westermann, Niklas Schofer, Sebastian Ludwig, Stefan Blankenberg, Michael Neuss, Marvin Bannehr, Tanja Kücken, Christoph Edlinger, Valentin Hähnel, Christian Butter, Fabien Praz, Mohammad Kassar, Nicolas Brugger, Thomas Pilgrim, Mirjam G. Winkel, Stephan Windecker, Aniela Petrescu, Stephan von Bardeleben, Roman Pfister, Christos Iliadis, Maria Körber, Viktor Mauri, Monique Wösten, Clemens Metze Stephan Baldus, Matthias Unterhuber, Philipp Lurz, Thilo Noack, Michael Borger, Stephan Blazek, Steffen Desch, Holger Thiele
Journal: JACC. Cardiovascular imaging (2020)
Cholesterol Levels In Patients With Newly Diagnosed Chronic Lymphocytic Leukemia: A retrospective Multicenter Study
Authors: Irfan Yavasoglu, Gokhan Pektas, Fergün Yilmaz, Gülsüm Akgün, Anil Tombak, Bila Toka, Sinan Dal, Hasan Ozbas, Guven Cetin, Ayhan Donmez, Oktay Bilgir, Naci Tiftik, Sehmuz Ertop, Orhan M. Ayyildiz, Mehmet Sonmez, Gurhan Kadikoylu, Murat Tombuloglu, Zahit Bolaman
Journal: Blood (2013)
Abstract LB-399: Late interferon-gamma blockade improves antitumor efficacy of anti-CTLA-4 and anti-PD-1 combination treatment
Authors: Stephen Mok, Renee Chin, James P. Allison
Journal: Cancer Research (2020)

Abstract The FDA has approved the use of immune checkpoint blockade antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) for cancer. Patients with metastatic melanoma that receive anti-CTLA-4 have a 22% 10-year overall survival rate, while those treated with anti-PD-1 have a 34% 5-year overall survival rate. The combination treatment of both mediates a 64% overall survival rate. Current literature suggests interferon signaling mediates the expression of inhibitory receptors such as programmed death-ligand 1 (PD-L1) in tumor microenvironment that may affect the responseivness to immunotherapy. However, the role of interferon signaling network throughout the timecourse of treatment remains unclear. In the B16F10 melanoma model, we first show that activated T-cells in combination treated mice produce more interferon-gamma (IFN-gamma) than naïve controls. Then, we have injected mice with anti-IFN-gamma antibody when 1) mice are first treated with combination CTLA-4/PD-1 blockade (early time point) and 2) the combination treatment is finished (late time point). We demonstrated that blocking IFN-gamma at the early time point compromises the antitumor efficacy of the combination treatment. In contrast, the antitumor efficacy of the combination treatment is improved and the expression of inducible co-stimulator (ICOS) on CD8 T-cells is increased if IFN-gamma is blocked at the late time point. Additionally, we found that the expression of PD-L1 in the tumor microenvironment is significantly reduced by IFN-gamma blockade at the late time point. Thus, we treated mice with anti-PD-L1 blocking antibody at the late time point and its antitumor tumor efficacy is similar to the mice treated with anti-IFN-gamma. It suggests that the improved antitumor efficacy of IFN-gamma blockade at the late time point in combination-treated mice is PD-L1 dependent. Collectively, we show that IFN-gamma has a complex and differential role throughout the time course of immunotherapy treatments, and this work suggests a potential combination treatment strategy with checkpoint blockade and late IFN-gamma blockade. Citation Format: Stephen Mok, Renee Chin, James P. Allison. Late interferon-gamma blockade improves antitumor efficacy of anti-CTLA-4 and anti-PD-1 combination treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-399.
TME‐Responsive Polyprodrug Micelles for Multistage Delivery of Doxorubicin with Improved Cancer Therapeutic Efficacy in Rodents
Authors: Shuguang Zhang, Peiyao Zhu, Jiayuan He, Siyuan Dong, Peiwen Li, Can Yang Zhang, Teng Ma
Journal: Advanced Healthcare Materials (2020)

Abstract It is of great significance to develop multifunctional biomaterials to effectively deliver anticancer drug to tumor cells for cancer therapy. Here, inspired by the specific tumor microenvironment (TME) cues, a unique multistage pH/redox‐responsive polyprodrug composed of amphiphilic pH‐sensitive diblock copolymer poly(ethylene glycol) methyl ether‐ b ‐poly( β ‐amino esters) conjugated with doxorubicin (DOX) via redox‐sensitive disulfide bonds (mPEG‐ b ‐PAE‐ss‐DOX) is designed and developed. This polyprodrug can self‐assemble into micelles (DOX‐ss@PMs) at low concentration with high serum stability, indicating that DOX‐ss@PMs have prolonged circulation time. The dual pH/redox‐responsiveness of the multistage platform is thoroughly evaluated. In vitro results demonstrate that DOX‐ss@PMs can highly accumulate at tumor site, followed by responding to the acidity for disassembly and effectively penetrating into the tumor cells. DOX is released from the platform due to the cleavage of disulfide bonds induced by high glutathione (GSH) concentration, thereby inducing the apoptosis of tumor cells. In vivo studies further reveal that multistage DOX‐ss@PMs can more efficiently inhibit the growth of tumors and improve the survival of tumor‐bearing mice in comparison to the free drug and control. These results imply that multistage delivery system might be a potential and effective strategy for drug delivery and DOX‐ss@PMs could be a promising nanomedicine for cancer chemotherapy.
A phase I and pharmacological study of MK-1775, a Wee1 tyrosine kinase inhibitor, in both monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors
Authors: J. H. Schellens, S. Leijen, G. I. Shapiro, A. C. Pavlick, R. Tibes, S. J. O'Day, T. Demuth, J. Viscusi, Y. Xu, A. M. Oza
Journal: Journal of Clinical Oncology (2009)

3510 Background: MK-1775 is an inhibitor of Wee1, a kinase that phosphorylates CDC2 to inactivate the CDC2/cyclin B complex (regulating the G2 checkpoint). Since most human cancers harbor p53-dependent G1 checkpoint abnormalities, they are dependent on the G2 checkpoint. G2 checkpoint abrogation may therefore sensitize p53 deficient tumor cells to anti-cancer agents. Methods: This study is evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-1775 administered as both monotherapy (MT) and combination therapy (CT) with gemcitabine (G), cisplatin (P), or carboplatin (C). PART 1 consists of a single dose of MK-1775 followed by 14 days observation. If well tolerated, the same pt continues on to one of three treatment arms in PART 2: a single lower dose of MK-1775 in combination with: 1) 1000 mg/m2 G, 2) 75 mg/m2 P or 3) C AUC 5. Maximum Tolerated Doses (MTDs) will be established for MK-1775 as both monotherapy and in combination. PD biomarkers include IHC analysis for pCDC2/CDC2 in plucked hair and skin biopsies, peripheral blood, and tumor biopsies. Wee1 gene expression signature is measured in plucked hair and tumor biopsies by qPCR. Results: To date, 37 pts (median age 61; up to 4 prior therapies) have been treated with MK-1775. 4 pts experienced DLT. One pt on G + 200mg MK-1775 had gr3 leucopenia and neutropenia; one pt on P + 200mg MK-1775 had gr3, fatigue, diarrhea and hypokalemia and another pt gr2 nausea/vomiting &gt; 48hrs requiring hospitalization. One pt on C + 325mg MK-1775 was hospitalized for gr3 bilirubin. Linear PK was demonstrated at 100, 200, 325, 650 and 1300 mg MK-1775. Terminal T½ of MK-1775 was 7.6–12.2 hrs and Tmax was 1.0–6.0 hrs. Preliminary MTDs of MK-1775 in combination with G, C and P were 200, 325 and 200mg, respectively. Significant changes in Wee1 signature gene expression were observed in plucked hair. Of 28 evaluable pts, &gt;50% regression of axillary lymphadenopathy was seen in 1 pt with melanoma on the P arm, and stable disease in 14 other pts (median duration). Conclusions: MK-1775 is a first in class Wee1 inhibitor that is well tolerated and shows promising anti-tumor activity in previously treated pts. [Table: see text]
I heard it as much as I felt it: my experience of a complete proximal hamstring rupture
Authors: Michelle Dyer
Journal: British Journal of Sports Medicine (2020)

I heard it as much as I felt it when the accident happened. I was waterskiing for the first time in 20 years and lost my balance as I was coming up out of the water. My legs straightened just as the boat hit speed and then I heard the snap. Thirty minutes later paramedics hauled me up the steep steps from the dock, strapped to a backboard, high over their heads. I was immediately worried about how this was going to impact my commitment to being active in my 40s and my new cycling hobby (figure 1).



Figure 1 
Michelle Dyer celebrating the completion of a charity cycle ride from London to Paris. Copyright: Michelle Dyer.



Theodore Woodward coined the phrase, “when you hear hoof beats, think of horses not zebras”. My consulting emergency room physician rightly assumed it was a hamstring strain—in his mind it was a horse. Back home in London 4 weeks later I met my sport and exercise medicine specialist, Dr Phil Batty at Isokinetic, who confirmed with his in-office ultrasound scanner that the muscle was retracted. This was a zebra—and not one for conservative management! He sent me for an MRI, which confirmed a full avulsion of the proximal hamstring tendon. It was 15 cm retracted, and I definitely needed surgery. …
Challenges to Professional Advancement Facing Women Surgeons—The View From Our Chairs
Authors: Janet E. Tuttle, Sharmila Dissanaike, Mary Killackey
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal