tbuckley/cabot-search huggingface dataset:
Prevention of Infanticide and Suicide in the Postpartum Period—the Importance of Emergency Care
Authors: Jurjen J. Luykx, Arianna Di Florio, Veerle Bergink
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
A multicenter, open label, uncontrolled, phase II clinical trial evaluating the safety and efficacy of venetoclax in combination with atezolizumab and obinutuzumab in richter transformation of CLL.
Authors: Marco Montillo, Davide Rossi, Emanuele Zucca, Anna Maria Frustaci, Stefano Pileri, Franco Cavalli, Alessandra Tedeschi
Journal: Journal of Clinical Oncology (2019)

TPS7575 Background: Diffuse large B-cell (DLBCL) transformation from chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), Richter Syndrome (RS), has poor prognosis. Venetoclax, Bcl-2 inhibitor, has shown activity either in DLBCL and DLBCL-type RS. Atezolizumab is a humanized immunoglobulin monoclonal antibody (MoAb) targeting PD-L1 on tumor-infiltrating immune cells or tumor cells and prevents interaction with the PD-1 receptor and B7.1. Obinutuzumab, anti CD-20 MoAb compared to rituximab, presents a greater antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis and direct cell death. Preliminary data of atezolizumab alone or in combination with obinutuzumab showed to be safe and promising in heavily pretreated DLBCL. We present a phase II trial evaluating safety and efficacy of venetoclax, atezolizumab, obinutuzumab combination in RS. Methods: Eligible pts are: ≥18 years, ECOG PS ≤2, diagnosis of DLBCL RS from CLL/SLL. Exclusion criteria: pretreated RS, prior therapy with venetoclax or atezolizumab, CNS involvement, history of autoimmune disease. The study consists of 2 phases. In the run-in phase 9 pts will be enrolled in three cohorts of 3 subjects each. If no more than 1 pt in each of the 3 groups experiences during the first 3 cycles: treatment-related death or grade 4 non-infective/non-hematologic adverse event; the expansion phase will follow enrolling up to 31 pts. Treatment consists of 35 cycles with: obinutuzumab (1000 mg C1-8), atezolizumab (1200 mg C1-18), venetoclax (400 mg/d C1-35). Primary endpoint of the study is safety and tolerability for the run-in phase; efficacy (overall response, complete remissions, response duration, progression free and overall survival) for the expansion phase. Safety and efficacy are also secondary endpoints of each phase. Exploratory consists of MRD monitored by flow cytometry and ultra-deep NGS of disease markers; correlation between outcome and disease biomarkers. EUDRACT 2018-005028-40. Clinical trial information: 2018-005028-40.
Prognostic significance of the maximal value of the baseline standardized uptake value on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for predicting pathologic malignancy of operable breast cancer.
Authors: Takayuki Kadoya, Kenjiro Aogi, Sachiko Kiyoto, Emiko Kanno, Etsushi Akimoto, Akiko Emi, Hideo Shigematsu, Norio Masumoto, Yoshifumi Sugawara, Morihito Okada
Journal: Journal of Clinical Oncology (2013)

11111 Background: [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is potentially useful in predicting prognosis of breast cancer patients. Methods: 344 breast cancer patients (mean age: 58.0 ± 12.5) with clinical stage IxIII between January 2006 and December 2011, were prospectively evaluated (median follow-up period: 52.0 months). Patients underwent a whole-body FDG PET/CT before operation. The maximal value of the baseline standardized uptake values (SUVmax) were assessed for predicting disease free survival (DFS). For the evaluation of relationship between SUVmax values and prognostic factors such as hormone receptors, human epidermal growth factor receptor 2 (HER2), nuclear grade, lymph node metastasis and tumor size, statistical analyses were performed using Student t test and log-rank test, and p values of less than 0.05 were considered to indicate statistically significant differences. Results: Clinical stage included were I (n =194), II (n=134) and III (n=16). Tumors with estrogen receptor (ER) positive were 292 (84.9%) and negative were 52 (15.1%). Patients were divided into two groups according to cut-off SUVmax established on the basis of receiver operating characteristic analysis (≤3.0 vs &gt;3.0, AUC=0.713). There was a significant difference in DFS between two groups (p=0.001) and, hormone receptor, HER2, nuclear grade, lymph node metastasis were found strong relation to SUVmax values. SUVmax and ER status were predictive factors with multivariable analysis using cox proportional hazard regression model (p=0.033 and p=0.004, respectively). Conclusions: SUVmax on FDG PET/CT before operation has a predictive value for high-grade malignancy and prognosis in operable breast cancer. [Table: see text]
Oral Janus kinase/SYK inhibition (ASN002) suppresses inflammation and improves epidermal barrier markers in patients with atopic dermatitis
Authors: Ana B. Pavel, Teresa Song, Hyun-Je Kim, Ester Del Duca, James G. Krueger, Celina Dubin, Xiangyu Peng, Hui Xu, Ning Zhang, Yeriel D. Estrada, Louis Denis, Niranjan Rao, Sandeep Gupta, David J. Zammit, Robert Bissonnette, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2019)
Chemotherapy-Induced Distal Enhancers Drive Transcriptional Programs to Maintain the Chemoresistant State in Ovarian Cancer
Authors: Stephen Shang, Jiekun Yang, Amir A. Jazaeri, Alexander James Duval, Turan Tufan, Natasha Lopes Fischer, Mouadh Benamar, Fadila Guessous, Inyoung Lee, Robert M. Campbell, Philip J. Ebert, Tarek Abbas, Charles N. Landen, Analisa Difeo, Peter C. Scacheri, Mazhar Adli
Journal: Cancer Research (2019)

Abstract Chemoresistance is driven by unique regulatory networks in the genome that are distinct from those necessary for cancer development. Here, we investigate the contribution of enhancer elements to cisplatin resistance in ovarian cancers. Epigenome profiling of multiple cellular models of chemoresistance identified unique sets of distal enhancers, super-enhancers (SE), and their gene targets that coordinate and maintain the transcriptional program of the platinum-resistant state in ovarian cancer. Pharmacologic inhibition of distal enhancers through small-molecule epigenetic inhibitors suppressed the expression of their target genes and restored cisplatin sensitivity in vitro and in vivo. In addition to known drivers of chemoresistance, our findings identified SOX9 as a critical SE-regulated transcription factor that plays a critical role in acquiring and maintaining the chemoresistant state in ovarian cancer. The approach and findings presented here suggest that integrative analysis of epigenome and transcriptional programs could identify targetable key drivers of chemoresistance in cancers. Significance: Integrative genome-wide epigenomic and transcriptomic analyses of platinum-sensitive and -resistant ovarian lines identify key distal regulatory regions and associated master regulator transcription factors that can be targeted by small-molecule epigenetic inhibitors.
In vitro and in vivo biocompatibility of Mg–Zn–Ca alloy operative clip
Authors: Pengfei Ding, Yuanchao Liu, Xianghui He, Debao Liu, Minfang Chen
Journal: Bioactive Materials (2019)

At present, titanium (Ti) and its alloys are most commonly use in hemostasis clip clinical applications. However, the Ti Clip cannot be absorbed in human body and produce artifacts on computed tomography (CT), and induce clinically relevant hypersensitivity in patients. In order to overcome the drawbacks of the non-degradable Ti clips, an Mg-Zn-Ca alloy operative clip was fabricated by combining hot extrusion and blanking processing. In vitro and in vivo biocompatibility of Mg-Zn-Ca alloy operative clip were evaluated by L-929 Cells and SD rat model respectively. It was found that Mg-Zn-Ca alloy exhibited non-cytotoxic to L929 cells. In vivo implantation showed that the newly designed Mg-Zn-Ca clip can successfully ligated carotid artery and no blood leakage occurred post-surgery. During the period of the clip degradation, a small amount of H2 gas formation and no tissue inflammation around the clips were observed. The degradation rate of the clip near the heart ligated the arteries faster than that of clip far away the heart due do the effect of arterial blood. Histological analysis and various blood biochemical parameters in rat serum samples collected at different times after clip implantation showed no tissue inflammation around the clips.
Response to: ‘Performance of the systemic lupus erythematosus disease activity score (SLE-DAS) in a Latin American population’ by Rodríguez-González<i>et al</i>
Authors: Diogo Jesus, Ana Matos, Carla Henriques, Margherita Zen, Andrea Doria, Luís Sousa Inês
Journal: Annals of the Rheumatic Diseases (2019)

It was with great interest that we read the letter ‘Performance of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) in a Latin American population’.1

Rodriguez-Gonzalez et al commented on our recent manuscript reporting the derivation and validation of Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS),2 which demonstrated a much higher performance to detect clinical meaningful changes of SLE disease activity, as compared with SLE Disease Activity Index 2000 (SLEDAI-2K).3

In their letter, Rodriguez-Gonzalez et al reported a cross-sectional monocentric cohort study of 227 Mexican Mestizo SLE patients, in which they found a very high positive correlation between the SLE-DAS and the SLEDAI-2K (rho=0.92, p<0.0001). These results are consistent with our published data in which we identified a very strong correlation between the SLE-DAS and the SLEDAI-2K in both the derivation and the external validation cohorts (rho=0.940 and 0.943, respectively, p<0.0005 for both).2

Moreover, Rodriguez-Gonzalez et al analysed the correlation of SLE-DAS and SLEDAI-2K in subgroups of patients defined according to the severity of disease …
Abstract LB-059: Hyperglycemia enhances cancer immune evasion by inducing alternative macrophage polarization through increased O-GlcNAcylation
Authors: Natalia Rodrigues Mantuano, Michal Stanczak, Isadora Oliveira, Alessandra Filardy, Ronan Silva, Alfred Zippelius, Adriane Regina Todeschini, Heinz Laubli
Journal: Cancer Research (2019)

Abstract Epidemiological studies have shown diabetes mellitus (DM) to significantly increase the risk for cancer and cancer progression. Hyperglycemia is the most important characteristic of DM and directly correlates with a poor prognosis in cancer patients. While enhanced availability of glucose can directly fuel tumor cell proliferation, the effect on the tumor immune microenvironment is less well known. Here, we demonstrate in vitro and in different murine tumor models that hyperglycemia induces an increased flux through the hexosamine biosynthetic pathway (HBP) in tumor-associated macrophages (TAMs) resulting in an upregulation of O-GlcNAcylation. Increased O-GlcNAcylation was associated with alternative M2 polarization of TAMs and reduced anti-tumor immunity. The effect of hyperglycemia on tumor growth was dependent on an intact adaptive immunity. Furthermore, inhibition of M2 polarization by the addition of anti-CSF1R antibodies abrogated the effect of hyperglycemia on tumor growth. Similarly, treatment of mice with inhibitors of the HBP or O-GlcNAcylation reduced M2 polarization of TAMs and reversed immune evasion of growing tumors. Finally, we find enhanced M2 polarization in chronically hyperglycemic patients with colorectal cancer compared to non-diabetic normoglycemic patients. Our findings provide a new and targetable mechanism of cancer immune evasion, advocating for strict control of hyperglycemia in cancer patients. Citation Format: Natalia Rodrigues Mantuano, Michal Stanczak, Isadora Oliveira, Alessandra Filardy, Ronan Silva, Alfred Zippelius, Adriane Regina Todeschini, Heinz Laubli. Hyperglycemia enhances cancer immune evasion by inducing alternative macrophage polarization through increased O-GlcNAcylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-059.
Abstract 606: Inhibition of Anastomotic Intimal Hyperplasia Using a Chimeric Decoy Strategy Against NFκB and E2F in a Rabbit Model
Authors: Takashi Miyake, Motokuni Aoki, Hirofumi Makino, Ryuichi Morishita
Journal: Circulation (2007)

Neointimal formation remains a major limitation after arterial reconstruction including prosthetic graft implantation. To overcome this problem, we focused on two important transcription factors, N...
Survival disparity in childhood acute lymphoblastic leukemia (CHD-ALL): Lessons from challenges in Nigeria (NGR).
Authors: Christopher Kwesi Oladipupo Williams
Journal: Journal of Clinical Oncology (2012)

e17013 Background: Survival disparity in CHD-ALL between developed (DVDC) and developing countries (DVPC) are linked to care assess gap but probably also to geographical variations in disease subtypes and biology. Methods: In 1982-1984, using international study protocol, 39 NGR ALL cases were immunophenotyped: in 18 &lt; 15 yr.old, 4 were "common" (c-) (%) (22.2), 2 null (11.1), 7 T (38.9 ), 4 B (22.2), and 1 (5.6) unclassifiable; in 21 ≥ 15 yr.old, these were 8 (38.1), 1 (4.8), 11 (52.4) 1 (4.8) and 0 (0.0) respectively, giving estimated CHD-ALL incidence (x10 -5 ) compared with DVDC as 0.8 vs 2.6 for ALL, and 0.18 vs 1.9 for c-, 0.31 vs 0.38 for T subtypes. Remission (RMS) induction course was with iv vincristine 2.0mg/m 2 /week x 4, and prednisolone 40mg/m 2 po daily x 28 days, iv doxorubicin hydrochloride 20-30mg/m 2 /day x 3 or cytosine arabinoside (ARA-C) 50mg/m 2 iv q12 hours days 1 to 7, and Cyclophosphamide 650mg/m 2 weekly x 2, this being repeated once in non-complete responders. Methotrexate (MTX) 12.5 mg/m 2 or ARA-C 50mg/m 2 was administered every 5 days x 6-8 doses intrathecally. Cranial irradiation and L-Asparaginase were not available. Complete and partial responders received 6-mercaptopurine 100mg/m 2 daily and MTX 12.5mg/m 2 per dose twice weekly as maintenance. RMS consolidation therapy was with 1-2 cycles of induction phase regimen but only 2 weeks of prednisolone. Results: Treatment (R x ) as planned (CR x ) vis-à-vis deviant incomplete R x were associated with RMS rate of 80% and 83%, mean RMS duration (days)157.8±115.3 and 83.4±52.2 (p&gt;0.05), survival duration 193.5±156.4 and 174.3±114.0 (p&gt;0.05). 25/26 patient had ≥1/7 adverse prognostic features. R x failure due to CNS complications was rare in CR x . Conclusions: R x outcomes were poor regardless of R x quality. While the R x regimen used differed from the contemporarily regimen in DVDC, equivalence in efficacy appeared likely, and unlikely to explain the failure pattern in NGR . Other explanations include the low CHD-ALL incidence in NGR as being due to the rarity of favorable and highly prevalent ALL subtypes of DVDC vis-à-vis less common poor prognostic subtypes of NGR. Improvement in CHD-ALL survival in DVPC requires novel R x in addition to improved access to care.
CRM1 expression in pancreatic carcinoma.
Authors: Amit Mahipal, Domenico Coppola, Shilpa Gupta, Barbara Centeno, Mokenge Peter Malafa
Journal: Journal of Clinical Oncology (2013)

e15115 Background: Increased expression of chromosomal region maintenance (CRM1) protein, also known as exportin 1, has been described in several human cancers. It is an important regulator of subcellular localization of tumor suppressor proteins and growth regulatory proteins. Direct inhibition of CRM1 blocks cell proliferation and induces apoptosis leading to the current evaluation of CRM1 inhibitors as anticancer agents in early phase clinical trials. There is a paucity of data regarding the prevalence of CRM1 expression in pancreatic cancer. Methods: We analyzed the expression of CRM1 by immunohistochemistry (IHC) in pancreatic tissue microarray (TMA) samples (malignant and non-malignant) obtained from patients who underwent potentially curative resection for pancreatic ductal adenocarcinoma. CRM1 antibody (Santa Cruz Biotechnology) was used for immunostaining the formalin fixed paraffin embedded core sections in the TMA samples. The intensity of staining and percentage of cells stained were graded on a scale of 0 to 3, with 3 being highest. The final IHC score was obtained using the product of immunostain intensity and percentage of cells stained (Range: 0-9). Low and high CRM1 expression was considered if the IHC score was 0 to 4 and 6 to 9 respectively. Results: Seventy nonmalignant and 91 pancreatic carcinoma samples were evaluated in this study. The median IHC score was 6 (range: 0-9) and 3 (range: 1-9) in malignant and nonmalignant pancreatic tissue samples respectively (P&lt;0.0001). High CRM1 expression was found in 11% (8/70) of normal tissue samples and 69% (63/91) of tumor samples (P&lt;0.0001). There were 48 paired samples of pancreatic cancer tissue and normal tissue obtained from same patient. Among these patients, 33 (69%) patients had higher CRM1 expression, 7 (15%) patients had similar expression and 8 (17%) patients had lower expression in malignant tissue sample as compared to their adjacent normal tissues. Conclusions: Higher CRM1 expression occurs frequently in pancreatic cancer as compared to nonmalignant pancreatic tissue, reinforcing its putative tumor oncogenic activity, and raising the value of targeting it for pancreatic cancer therapy.
Outcomes of HIV patients treated with chemoradiotherapy (CRT) for squamous cell carcinoma of the head and neck (SCCHN).
Authors: Waleed Fouad Mourad, Kenneth Hu, Rania Ayman Shourbaji, Zujun Li, Bruce Culliney, Louis Benjamin Harrison
Journal: Journal of Clinical Oncology (2012)

5531 Background: SCCHN with HIV is a challenging clinical situation in the medical arena due to limited data. We report our outcomes and the impact of chemotherapy (CT) and HPV on this patient (pt) population Methods: This is a single institution retrospective study of 71 HIV pts with SCCHN treated from 1998-2011. The median age at RT and HIV diagnosis was 51 (32-72) and 34 (25-50) respectively. HIV duration was 11 yrs (6-20). Stage I-II, III and IV were 22, 27 and 51% respectively. Pts treated with RT alone were 37% and CRT 63% {CDDP 91%}. Fifty pts were on HAART during treatment and 50% of pts with SCC of the oropharynx were HPV+. Median dose of 70, 63 and 54 Gy were delivered at 1.8-2 Gy/fraction to gross disease, high and low risk neck respectively. Twelve pts (17%) underwent neck dissection for N3 Results: With a median follow up of 50 months (12-140) the median weight loss was 20 lbs (6-40). Acute skin desquamation and mucositis grades ≤ 2 and 3 were 76 and 24% respectively. Treatment breaks ≥ 10 and 5 days were 7 and 21% respectively. One pt died from induction CT, 1 was hospitalized for grade 4 mucositis and 1 developed osteoradionecrosis during CRT. Late dysphagia grades ≤ 2, 3 and 4 were 74, 15 and 11%. Late xerostomia grades ≤ 2 and 3 were 77 and 23% respectively. The median CD4 count and viral load before, during and after treatment were 370, 135, 100 and 0, 160, 260 respectively. Seven pts (10%) developed second primary malignancy. The 4 yr locoregional control (LRC) and overall survival (OS) were 69% and 55% respectively. Chi-square test shows significant relationship between LRC and RT duration, as well as between CT and lower CD4 counts and higher viral load (P=0.001). Positive trends were observed between (weight loss ≤10% and LRC) and (absence of second malignancy and OS) (P=0.271). There was no significant relationship between HPV +ve or CT on either LRC or OS. Conclusions: The addition of CT to RT yielded higher morbidity and mortality without clear benefit on LRC or OS. HIV per se seems to have a -ve impact on HPV +ve pts outcomes. Comparing observed rates of LRC and OS, our data show that RT±CT administered for HIV +ve pts with SCCHN appears to be less effective than HIV-ve pts. Larger size studies are warranted to optimize the management of this growing patient population.
Automated quantum dots <i>ISH</i> assay for detection of ERG rearrangement and PTEN deletion in prostate cancer.
Authors: Lei Tang, Wenjun Zhang, Antony Hubbard, Patrick S Brunhoeber, Yixin Wang
Journal: Journal of Clinical Oncology (2013)

5045 Background: ERG rearrangement and PTEN deletion are the two most common genomic events in prostate cancer. Overexpression of the ERG protein caused by rearrangement of the ERG gene has been frequently associated with more aggressive prostate cancers and a poor prognosis. PTEN genomic deletion and absence of PTEN expression are associated with unfavorable clinical outcome. To detect ERG rearrangement and PTEN deletion simultaneously, we developed a four-color multiplex ISH assay using non-organic quantum dots (QD). The photo-stability and narrow emission spectra of QDs makes them desirable for ultrasensitive and multiplexing ISH applications. The automated QD ISH assay allows adequate delivery of QDs to nuclear targets and reproducible detection of ERG and PTEN gene targets. Methods: DNA probes specific for ERG 5’, ERG 3’, PTEN and CEN 10 were labeled with different haptens, digoxigenin (DIG), dinitrophenyl (DNP), thiazole sulfonamide (TS), or nitropyrazole (NP). QDs with 565, 655, 605 and 525nm wavelengths were conjugated to the anti- DIG, DNP, TS or NP antibodies, respectively. The multiplex QD ISH assay was fully automated on the VENTANA BenchMark ULTRA. FFPE prostate tissue slides were hybridized with the labeled probes. The probes were then detected by the QD-conjugated antibodies and visualized under fluorescent microscope. Results: We performed the multiplex QD ISH assay on 386 slides with tissue sections from 10 prostate specimens on 13 BenchMark ULTRA instruments. The 10 cases consisted of either benign prostate tissues or prostate cancer, positive or negative for ERG rearrangement and/or PTEN deletion. 350 (91%) of the slides were successfully stained for all 4 molecular targets. The expected ERG and PTEN status were detected with high reproducibility. Conclusions: We developed an automated QD based multiplex ISH assay to simultaneously detect ERG rearrangement and PTEN deletion in prostate cancer. The assay is highly sensitive and reproducible. It enables investigation of potential clinical use of ERG and PTEN as predictive or prognostic markers. In addition, the same technology is expected to enable multiplex in situ detection of other molecular biomarkers using standard clinical specimens.