tbuckley/cabot-search huggingface dataset:
Seronegative Myasthenia Gravis—A Vanishing Disorder?
Authors: Henry J. Kaminski
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology 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 Neurology journal
A phase II study of capecitabine, oxaliplatin, and bevacizumab for metastatic or unresectable neuroendocrine tumors.
Authors: P. L. Kunz, T. Kuo, J. M. Zahn, H. L. Kaiser, J. A. Norton, B. C. Visser, T. A. Longacre, J. M. Ford, R. R. Balise, G. A. Fisher
Journal: Journal of Clinical Oncology (2010)

4104 Background: Neuroendocrine tumors (NETs) are a rare and heterogeneous class of neoplasms. They frequently metastasize to the liver and have a unique hypervascular appearance, making this class of tumors an interesting target for angiogenesis inhibition. Methods: Patients (pts) with biopsy proven metastatic or unresectable neuroendocrine tumors received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m2 IV on day 1 and capecitabine 850 mg/m2 twice daily by mouth on days 1-14 on a 21-day cycle. Pts with stable disease (SD) or partial response (PR) were allowed to continue therapy with bevacizumab with or without capecitabine. Primary endpoints were progression free survival (PFS) and toxicity; secondary endpoints were overall survival (OS) and response rate by RECIST. Results: Between December 2006 and October 2009, 40 pts enrolled, 31 pts are available for response assessment, 6 patients came off study prior to their first tumor assessment, and 3 others are not yet evaluable for response. At a median follow-up of 11.4 months, 11 pts are still on study. Baseline characteristics were: M:F = 22:18, median age = 55 (range 32-76), primary site = pancreas (20), small intestine (5) and unknown/other (15). Pathology was reviewed on 37 pt samples; Ki67 > 20% (n = 7) and 0-20% (n = 30). PRs were observed in 7 pts (23%), SD in 22 pts (71%), and progressive disease (PD) in 2 pts (6%). Of the pts who achieved a PR, 6 had pancreatic NETs and one had an unknown primary with liver involvement. The 1-year PFS is 52% and median PFS is 13.7 months. The treatment was well-tolerated. A discovery panel of 15 biomarkers was evaluated at baseline and cycle 4 in 22 patients. Serum levels of CHI3L1 (YKL-40) drawn at baseline correlated with PFS and OS (HR 1.64 and 1.98 respectively; p < 0.05 [not adjusted for multiple comparisons]). VEGF levels increased on average 1.5 fold over 4 cycles of therapy (0.5-9.7 fold ± 2.4). Conclusions: The combination of capecitabine, oxaliplatin and bevacizumab in metastatic or unresectable neuroendocrine tumors is well tolerated and shows promising efficacy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech/Roche, sanofi-aventis
Effects of 5-hydroxytryptophan on fragmentation of REM sleep in alcoholics
Authors: V P Zarcone, E Hoddes
Journal: American Journal of Psychiatry (1975)

The authors studied the effects of oral loading with 5-HTP on REM fragmentation in a group of alcoholics who were abstinent following acute ethanol withdrawal. Decreased fragmentation was found in the majority of subjects, and those subjects with low baseline REM efficiency (i.e., greater fragmentation) showed more improvement from the drug than did subjects who were less impaired initially. The authors suggest that there is an organic decrement of serotonin during ethanol withdrawal which is partially reversed by 5-HTP loading.
FDA Approval: Alectinib for the Treatment of Metastatic, ALK-Positive Non–Small Cell Lung Cancer Following Crizotinib
Authors: Erin Larkins, Gideon M. Blumenthal, Huanyu Chen, Kun He, Rajiv Agarwal, Gerlie Gieser, Olen Stephens, Eias Zahalka, Kimberly Ringgold, Whitney Helms, Stacy Shord, Jingyu Yu, Hong Zhao, Gina Davis, Amy E. McKee, Patricia Keegan, Richard Pazdur
Journal: Clinical Cancer Research (2016)

Abstract On December 11, 2015, the FDA granted accelerated approval to alectinib (Alecensa; Genentech) for the treatment of patients with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive, metastatic non–small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This approval was based on two single-arm trials including 225 patients treated with alectinib 600 mg orally twice daily. The objective response rates (ORR) by an independent review committee in these studies were 38% [95% confidence interval (CI), 28–49] and 44% (95% CI, 36–53); the median durations of response (DOR) were 7.5 months and 11.2 months. In a pooled analysis of 51 patients with measurable disease in the central nervous system (CNS) at baseline, the CNS ORR was 61% (95% CI, 46–74); the CNS DOR was 9.1 months. The primary safety analysis population included 253 patients. The most common adverse reactions were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%). The most common laboratory abnormalities were anemia (56%), increased aspartate aminotransferase (51%), increased alkaline phosphatase (47%), increased creatine phosphokinase (43%), hyperbilirubinemia (39%), hyperglycemia (36%), increased alanine aminotransferase (34%), and hypocalcemia (32%). Dose reductions due to adverse reactions occurred in 12% of patients, whereas 27% of patients had alectinib dosing interrupted for adverse reactions. Permanent discontinuation of alectinib due to adverse reactions occurred in only 6% of patients. With the clinically meaningful ORR and DOR as well as the safety profile observed in these trials, alectinib was determined to have a favorable benefit–risk profile for the treatment of the indicated population. Clin Cancer Res; 22(21); 5171–6. ©2016 AACR.
Case 49-1968
Authors: Rita M. Kelley, Benjamin Castleman
Journal: New England Journal of Medicine (1968)

Presentation of Case First admission. A sixty-nine-year-old woman entered the hospital for removal of a vocal-cord polyp.For twelve years she had had episodes of respiratory distress and wheezing, which were treated with a bronchodilator medication. She habitually smoked 2 packages of cigarettes daily and had a chronic productive cough. One year before admission slight elevation of the blood pressure was found. Five months before entry vocal-cord polyps were removed at another hospital. At about that time she noticed loss of vision, and an intraocular hemorrhage was found in the left eye. Moderate polydipsia occurred, but no polyuria. Shortly before . . .
P-289 Hepatic arterial infusion chemotherapy for unresectable liver metastases of colorectal cancer: a multicenter retrospective study
Authors: A. Lim, S. Le Sourd, H. Senellart, D. Luet, F. Douane, C. Perret, A. Bouvier, S. Métairie, E. Cauchin, Rougier Philippe, Matysiak-Budnik Tamara, Y. Touchefeu
Journal: Annals of Oncology (2016)
Allergy to Drugs
Authors: Edward A. Carr
Journal: New England Journal of Medicine (1951)

Further Consideration of Certain DrugsUrticaria due to penicillin has two features that deserve comment: It may subside while the drug is still being administered147 or fail to recur on readministration,196 or it may, on the other hand, recur in waves for a period of one to two months after administration of penicillin has been stopped.197 It is difficult to understand why the reaction some-times subsides despite continuation of the drug, but this paradox has been noted at times in other allergies to drugs, such as agranulocytosis. Spontaneous loss of the altered capacity, occurring after administration has stopped, is also . . .
A double-blind randomized phase II study of 10 versus 5 mg olanzapine for emesis induced by highly emetogenic chemotherapy with cisplatin.
Authors: Hironobu Hashimoto, Takako Yanai, Kengo Nagashima, Natsuko Okita Tsuda, Hidehito Horinouchi, Tomomi Takiguchi, Fumiyoshi Ohyanagi, Masahiko Nakao, Koji Takeda, Toshiaki Nakayama, Hiroshi Sakai, Takahiro Arai, Koichi Minato, Yuki Kogure, Daijiro Harada, Kenichi Suzuki, Narikazu Boku, Yasuhiro Shimada, Satoru Iwasa, Noboru Yamamoto
Journal: Journal of Clinical Oncology (2016)

10111 Background: The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine (OLZ) in combination with standard antiemetic treatment (aprepitant [APR], palonosetron [PALO], and dexamethasone [DEX]) to determine the better dose of OLZ as a test arm in a subsequent placebo controlled phase III study for patients receiving highly emetogenic chemotherapy (HEC). Methods: A multi-institutional, double-blind, randomized phase II, dose-finding study of OLZ was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (CDDP, ≥ 50 mg/m2). Patients were randomly assigned either OLZ 10 or 5 mg orally after supper on days 1–4, combined with APR (125 mg p.o. on day 1, 80 mg p.o. on days 2–3), PALO (0.75 mg i.v. on day 1) and DEX (9.9 mg i.v. on day 1 and 6.6 mg i.v. on days 2–4). The primary endpoint was a complete response (CR), defined as no emetic episodes and rescue medications used in the delayed phase (24 to 120 h). At least 72 patients were required in each arm based on the hypothesis of expecting a CR rate of 75% (65% for the null hypothesis), with 75% power and a one-sided significance of 0.10 using a closed testing procedure. Results: Between July 2014 and March 2015, 153 patients were enrolled. The CR rate during the delayed phase was 77.6% (80% CI, 70.3–83.8, p = 0.01) for the 10 mg OLZ group and 85.7% (80% CI, 79.2–90.7, p < 0.001) for the 5 mg OLZ group (p-value for H0: CR rate ≤ 65% (historical control)). Other efficacy results are summarized in the table. The most common adverse event was somnolence, with incidences of 53.3% and 45.5% in the 10 and 5 mg OLZ groups, respectively. Conclusions: Both doses of 10 and 5 mg OLZ provided a significant improvement in delayed emesis. A dose of 5 mg OLZ was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates. Clinical trial information: UMIN000014214. OLZ 10 mg (n=76) OLZ 5 mg (n=77) % 80%CI % 80%CI CR rate Acute 100.0 97.0-100.0 98.7 95.0-99.9 Delayed 77.6 70.3-83.8 85.7 79.2-90.7 Overall 77.6 70.3-83.8 85.7 79.2-90.7 TC rate* Acute 89.5 83.5-93.8 92.2 86.7-95.9 Delayed 61.8 53.9-69.3 64.9 57.1-72.2 Overall 59.2 51.2-66.8 62.3 54.4-69.7 *TC: no nausea, emetic episodes and rescue medications.
Tumors of the Glandular Stomach Induced in Rats by Intramural Injection of 20-Methylcholanthrene
Authors: William V. Habe, M. D., Harold L. Stewart, M. D., James G. Bennett, M. D., Egon Lorenz, Ph. D.
Journal: JNCI Journal of the National Cancer Institute (1952)

Journal Article Tumors of the Glandular Stomach Induced in Rats by Intramural Injection of 20-Methylcholanthrene Get access William V. Habe, M. D., William V. Habe, M. D. National Cancer Institute4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold L. Stewart, M. D., Harold L. Stewart, M. D. National Cancer Institute4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar James G. Bennett, M. D., James G. Bennett, M. D. National Cancer Institute4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Egon Lorenz, Ph. D. Egon Lorenz, Ph. D. National Cancer Institute4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 5, April 1952, Pages 1019–1055, https://doi.org/10.1093/jnci/12.5.1019 Published: 01 April 1952 Article history Received: 11 December 1951 Published: 01 April 1952
PD-027 BRAF mutant and RAS mutant patients treated with FOLFIRI plus Bevacizumab or FOLFIRI plus Cetuximab. Role of ETS and molecular markers in FIRE-3 (AIO KRK-0306)
Authors: S. Stintzing, L. Fischer von Weikersthal, T. Decker, A. Kiani, U. Vehling-Kaiser, S.-E. Al-Batran, T. Heintges, C. Lerchenmüller, C. Kahl, G. Seipelt, F. Kullmann, M. Stauch, J. Hielscher, M. Lerch, W. Scheithauer, A. Jagenburg, S. Held, D. Modest, A. Jung, T. Kirchner, V. Heinemann
Journal: Annals of Oncology (2016)
Analysis of Mesenchymal Stromal Cells (MSC) and Their Interactions with CD34 Stem and Progenitor Cells in Patients with Myelodysplastic Syndromes (MDS)
Authors: Stefanie Geyh, Ron Patrick Cadeddu, Julia Fröbel, Ingmar Bruns, Fabian Zohren, Ali-Nuri Hünerlitürkoglu, Guido Kobbe, Norbert Gattermann, Ulrich Germing, Rainer Haas, Thomas Schroeder
Journal: Blood (2011)
Haunted House
Authors: M Therese Southgate
Journal: JAMA (2005)

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
Retroviral Insertional Mutagenesis In Egr1+/- mice, Haploinsufficient For a Human Del(5q) Myeloid Leukemia Gene, Develop Myeloid Neoplasms With Proviral Insertions In Genes Syntenic To Human 5q
Authors: Angela Stoddart, Anthony Fernald, Rachel Joy Bergerson, Jianghong Wang, Megan E. McNerney, Theodore Karrison, John Anastasi, Elizabeth Bartom, Aaron G. Sarver, Zhijian Qian, Linda Wolff, David A. Largaespada, Michelle M. le Beau
Journal: Blood (2013)
Summary of Notifiable Noninfectious Conditions and Disease Outbreaks: Introduction to the Summary of Notifiable Noninfectious Conditions and Disease Outbreaks — United States
Authors: Ralph J. Coates, Ruth Ann Jajosky, Martha Stanbury, Steven C. Macdonald
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Abbreviations: CIC = U.S. Bureau of the Census industry codes; FTE = full time equivalent; SENSOR = Sentinel Event Notification System for Occupational Risks.* Information on industry was missing for 262 (13%) persons with cases of pesticide-related illness.† Estimates were derived from the hours worked data obtained from the U.S. Current Population Survey (CPS) and summed for the years 2007-2010 (8).One FTE equals 2,000 hours worked.Denominator data correspond to the states and time periods of numerator availability.§ Incidence rate per 100,000 FTEs.Abbreviations: CIC = U.S. Bureau of the Census industry codes; SENSOR = Sentinel Event Notification System for Occupational Risks.* Includes plant growth regulators, insect growth regulators, wood treatment products, preservatives, and insect repellants.† Exposed to pesticide products that were classified into more than one functional class or to more than one pesticide product
Enhanced Global Hemostatic Potentials with a Bispecific Antibody to Factors IXa and X (ACE910) in the Whole Blood By Rotation Thromboelastometry (ROTEM)
Authors: Koji Yada, Keiji Nogami, Yasuaki Shida, Masahiro Takeyama, Ryu Kasai, Midori Shima
Journal: Blood (2015)
Antibody-Targeted Chemotherapy with Immunoconjugates of Calicheamicin: Differential Anti-Tumor Activity of Conjugated Calicheamicin Targeted to B-Cell Lymphoma Via B-Cell Lineage Specific Molecules CD19, CD20 and CD22.
Authors: John F. DiJoseph, Douglas C. Armellino, Maureen M. Dougher, Arthur Kunz, Erwin R. Boghaert, Philip R. Hamann, Karen Zinkewich-Peotti, Nitin K. Damle
Journal: Blood (2004)
Frequency of JAK2 Exon 12 Mutations in JAK2 Exon 14 V617F-Negative Patients: High Frequency in ET Patients.
Authors: Veronique M. Duke, Nicole Gurunlian, Bi Yogashangari, Tom Colley, Christopher McNamara, A. Victor Hoffbrand, Letizia Foroni
Journal: Blood (2007)
Successful biliary drainage with peroral direct cholangioscopy in a patient with Roux-en-Y hepaticojejunostomy for congenital biliary dilatation
Authors: Kazuyuki Matsumoto, Koichiro Tsutsumi, Yuki Baba, Koji Takemoto, Hirofumi Tsugeno, Shigeatsu Fujiki, Hiroyuki Okada
Journal: Endoscopy (2015)

The diagnostic and therapeutic effectiveness of combined double-balloon endoscopy with a short endoscope and peroral direct cholangioscopy with an ultraslim endoscope in patients who have altered gastrointestinal anatomy has been demonstrated [1] [2] [3] [4] [5]. We describe successful biliary drainage with a short double-balloon endoscope and peroral direct cholangioscopy in a patient who had cholangitis after surgery for congenital biliary dilatation.
Is the platinum-based chemotherapy necessary for elderly patients with advanced non-small cell lung cancer (NSCLC)?
Authors: H. Daga, K. Takeda, H. Kiyota, S. Tokunaga, S. Nanjo, M. Sumitani, S. Shoji
Journal: Journal of Clinical Oncology (2008)

19088 Background: Single-agent chemotherapy as a first-line treatment is currently considered as the standard approach for elderly patients with advanced NSCLC. Since the platinum-based combination chemotherapy is the standard treatment for younger patients with advanced NSCLC, it may also have more effective for elderly. We reviewed the chart records of elderly advanced NSCLC patients treated with any chemotherapy in our hospital. Methods: We undertook retrospective reviews in 178 elderly advanced NSCLC patients, who were more than 70 years old and received any chemotherapy in our hospital from 1996 to 2005. Survival curves were made up by Kaplan-Maier method and compared using the log-rank test. Multivariate analysis was performed by the Cox’s proportional hazard model. Results: In 178 elderly patients, 109 (61.2%) aged 70–74 years old and 69 (38.8%) aged 75 years or older were classified. There was no difference in backgrounds, which were gender, histology (adenocarcinoma or non-adenocarcinoma), and ECOG PS (0–1 or 2), between the two groups. However, there was significant difference of the treatment regimen (platinum-based combination or single agent [non platinum- based]) when we made the determination on the basis of our treatment policy. Platinum-based chemotherapy was selected more in aged 70–74 patients (65 pts; 59.6%) than aged 75 years or older patients (16 pts; 23.2%), therefore, single agent chemotherapy was more selected for aged 75 years or older patients. There was no statistical difference in median overall survival with platinum-based chemotherapy group and non platinum-based chemotherapy group (10.4 months vs 9.9 months, P =0.3647). The prognostic factors in multivariate analysis were PS 0–1, female, and adenocarcinoma, but platinum-based chemotherapy was not good prognostic factor, furthermore, patients aged 75 years or older had not poor survival. Conclusions: Platinum-based chemotherapy was not necessary for elderly patients with advanced NSCLC in this review. While retrospective studies have several limitations, prospective randomized controlled trial comparing platinum-based chemotherapy with single agent chemotherapy for elderly patients with advanced NSCLC is conducted in Japan. No significant financial relationships to disclose.
Information
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1972)

ACCORDING to the linguistic school currently on top, human beings are all born with a genetic endowment for recognizing and formulating language. This must mean that we possess genes for all kinds of information, with strands of special, peculiarly human DNA for the discernment of meaning in syntax. We must imagine the morphogenesis of deep structures, built into our minds, for coding out, like proteins, the parts of speech. Correct grammar (correct in the logical, not fashionable, sense) is as much a biologic characteristic of our species as feathers on birds.If this is true, it would mean that the . . .
Age at onset and number of psychotic symptoms in bipolar I and schizoaffective disorder
Authors: L N Rosen, N E Rosenthal, P H Van Dusen, D L Dunner, R R Fieve
Journal: American Journal of Psychiatry (1983)

The authors rated 71 bipolar I patients on the basis of the number of different psychotic symptoms experienced during the course of their illness. Patients who became ill at a young age had significantly higher scores than patients with a later onset.
Brexit: the decision of a divided country
Authors: Danny Dorling
Journal: BMJ (2016)

Blame austerity not immigration for the inequality underlying the referendum decision

On the same day that the United Kingdom voted to leave the EU, huge rises in UK death rates were reported. These rises followed the austerity policies enacted by the 2010 coalition government.1 Self reported health was a key component of David Cameron’s wellbeing index, and it has declined in every year of his premiership, most rapidly towards the end.2 In March 2016 the Office for National Statistics (ONS) reported: “The proportion of people aged 16 and over in the UK who were somewhat, mostly or completely satisfied with their health was lower in the financial year ending 2014 (57.8%) than in the previous year (59.3%). The way in which people view their health is crucial to well-being.”3

Brandishing the slogan “Vote leave, take control,”4 the Leave campaign secured 51.9% of the referendum vote. However, 13 million registered voters did not vote, …
Early-life stress leads to impaired spatial learning and memory in middle-aged ApoE4-TR mice
Authors: Lan-yan Lin, Jing Zhang, Xiao-man Dai, Nai-an Xiao, Xi-lin Wu, Zhen Wei, Wen-ting Fang, Yuan-gui Zhu, Xiao-chun Chen
Journal: Molecular Neurodegeneration (2016)

Apolipoprotein E (ApoE) is a major lipid carrier that supports lipid transport and injury repair in the brain. The APOE ε4 allele is associated with depression, mild cognitive impairment (MCI) and dementia; however, the precise molecular mechanism through which ApoE4 influences the risk of disease development remains unknown. To address this gap in knowledge, we investigated the potential effects of chronic unpredictable mild stress (CUMS) on ApoE3 and ApoE4 target replacement (ApoE3-TR and ApoE4-TR) mice. All ApoE-TR mice exposed to CUMS at 3 months old recovered from a depression-like state by the age of 12 months. Of note, ApoE4-TR mice, unlike age-matched ApoE3-TR mice, displayed impaired spatial cognitive abilities, loss of GABAergic neurons, decreased expression of Reelin, PSD95, SYN and Fyn, and reduced phosphorylation of NMDAR2B and CREB. These results suggest that early-life stress may mediate cognitive impairment in middle-age ApoE4-TR mice through sustained reduction of GABAergic neurons and Reelin expression, which might further diminish the activation of the Fyn/NMDAR2B signaling pathway.