tbuckley/cabot-search huggingface dataset:
Coining
Authors: C E Crutchfield, T J Bisig
Journal: New England Journal of Medicine (1995)

Figure 1. Linear microecchymoses, produced by rubbing the edge of a coin on the skin, are visible on a 33-year-old Vietnamese man who had been using this traditional Southeast Asian treatment unsuccessfully for recurrent migraine headaches. The erythematous stripes usually disappear after one to two weeks, but hyperpigmentation may persist. The lesions from this home remedy should not be mistaken for a manifestation of abuse.
Induced pluripotent stem cells in Alzheimer’s disease: applications for disease modeling and cell-replacement therapy
Authors: Juan Yang, Song Li, Xi-Biao He, Cheng Cheng, Weidong Le
Journal: Molecular Neurodegeneration (2016)

Alzheimer's disease (AD) is the most common cause of dementia in those over the age of 65. While a numerous of disease-causing genes and risk factors have been identified, the exact etiological mechanisms of AD are not yet completely understood, due to the inability to test theoretical hypotheses on non-postmortem and patient-specific research systems. The use of recently developed and optimized induced pluripotent stem cells (iPSCs) technology may provide a promising platform to create reliable models, not only for better understanding the etiopathological process of AD, but also for efficient anti-AD drugs screening. More importantly, human-sourced iPSCs may also provide a beneficial tool for cell-replacement therapy against AD. Although considerable progress has been achieved, a number of key challenges still require to be addressed in iPSCs research, including the identification of robust disease phenotypes in AD modeling and the clinical availabilities of iPSCs-based cell-replacement therapy in human. In this review, we highlight recent progresses of iPSCs research and discuss the translational challenges of AD patients-derived iPSCs in disease modeling and cell-replacement therapy.
NHS regulator will do fewer inspections as budgets are cut
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Providers of health services in England will be inspected less often and in less depth if they are considered to be performing well, under plans by the NHS regulator the Care Quality Commission to streamline its operations. But doctors’ leaders have said that the planned changes do not go far enough in reducing the burden of inspection on clinicians.

The CQC published its five year strategy for 2016 to 2021 on Tuesday 24 May, in which it said that it wanted to bring in a more “targeted, responsive and collaborative” approach to regulation.1

A key change in its approach will be a move towards better use of information from the public, healthcare providers, other regulators, and oversight bodies to allow resources to …
Case 43-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, David Littmann
Journal: New England Journal of Medicine (1971)

Presentation of CaseA 70-year-old woman was transferred from another hospital because of persistent congestive heart failure.Seven years previously she was found to have diabetes mellitus, and a diabetic diet and tolbutamide were begun. Five years before admission she had a single, transient episode of left-sided weakness. One year later there was the onset of dyspnea. Two years before admission a film of the chest was normal except for questionable evidence of pulmonary venous hypertension. Three months before entry the dyspnea increased in severity, with the development of peripheral edema, abdominal distention and palpitation. Five weeks before admission she . . .
A comparison of the cortisol suppression index and the dexamethasone suppression test in prepubertal children
Authors: R A Weller, E B Weller, M A Fristad, M L Cantwell, S H Preskorn
Journal: American Journal of Psychiatry (1985)

Results of the dexamethasone suppression test (DST) and the cortisol suppression index (CSI) were compared in 50 depressed prepubertal children and 36 control subjects. The 4:00 p.m. DST, the two-point DST, and the 8:00 a.m. revised criterion CSI yielded the best results and had similar clinical utility and diagnostic confidence values.
Phase 1/2a study of double immune suppression blockade by combining a CSF1R inhibitor (pexidartinib/PLX3397) with an anti PD-1 antibody (pembrolizumab) to treat advanced melanoma and other solid tumors.
Authors: Zev A. Wainberg, Peter D. Eisenberg, Jasgit C. Sachdev, Amy M. Weise, David Ross Kaufman, Marguerite Hutchinson, Sandra Tong, Ireene Aromin, Siwen Hu-Lieskovan, Amita Patnaik
Journal: Journal of Clinical Oncology (2016)

TPS465 Background: Tumor-associated macrophages (TAMs) support tumor growth and cause tumor resistance to chemotherapy and radiation therapy; myeloid-derived suppressor cells (MDSCs) suppress anti-tumor immunity and cause resistance to PD-1 inhibition. TAMs and MDSCs are both regulated by colony stimulating factor 1 (CSF1). Pexidartinib is a small molecule inhibitor of CSF1 receptor, CSF1R. The normal function of PD-1, expressed on the cell surface of activated T-cells, is to suppress excessive immune responses, eg, autoimmune reactions. Tumors utilize PD-1 signaling to downregulate immune-mediated elimination. Pembrolizumab is a potent, highly selective humanized monoclonal antibody that blocks interactions between PD-1 and its ligands, PD-L1 and PD-L2. We present the study design for a Phase 1/2a clinical trial assessing safety, efficacy, pharmacokinetics, and pharmacodynamics of the combination of pexidartinib and pembrolizumab in advanced solid tumors (NCT02452424). Methods: In Part 1 of this open-label, uncontrolled trial, patients with advanced solid tumors will receive pembrolizumab (200 mg IV q 3 weeks) and escalating daily oral doses of pexidartinib to establish the safety and tolerability of the combination and a recommended phase 2 dose (RP2D). In Part 2, the combination RP2D will be studied in an expanded panel of solid tumor cohorts in up to 475 patients, to assess safety and preliminary efficacy. The panel will include GI malignancies for which preclinical data support this combination, including gastric and gastro-esophageal adenocarcinoma, pancreatic cancer, cholangiocarcinoma, and GI stromal tumors. Overall response rate (RECISTv1.1) and progression free survival will be evaluated. Exploratory endpoints include novel biomarkers of clinical activity and drug mechanisms of action. A truncated sequential probability ratio test will be employed in each tumor cohort to allow early decision-making for futility or success. The results will support further development of the pexidartinib/pembrolizumab combination in the solid tumors that respond to treatment in this study. Clinical trial information: NCT02452424.
Spontaneous Lesion of Stomach in Strain I Mice&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article Spontaneous Lesion of Stomach in Strain I Mice Get access Howard B. Andervont Howard B. Andervont National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 2, October 1949, Pages 405–406, https://doi.org/10.1093/jnci/10.2.405 Published: 01 October 1949
Conflicting treatment models for the inpatient management of borderline patients
Authors: C Gordon, E Beresin
Journal: American Journal of Psychiatry (1983)

The authors contrast two paradigms for long-term treatment of borderline patients: 1) modified psychoanalytic psychotherapy, which attempts to bring about structural intrapsychic change, and 2) psychotherapy that strives only to improve adaptation. They demonstrate the divergent uses of the psychiatric hospital for these two treatments and the potential for regression and hospital failure when conceptual conflict arises between inpatient and outpatient clinicians or when the hospital mixes aspects of these often antithetical treatment models.
Reward Processing, Neuroeconomics, and Psychopathology
Authors: David H. Zald, Michael T. Treadway
Journal: Annual Review of Clinical Psychology (2017)

Abnormal reward processing is a prominent transdiagnostic feature of psychopathology. The present review provides a framework for considering the different aspects of reward processing and their assessment, and highlights recent insights from the field of neuroeconomics that may aid in understanding these processes. Although altered reward processing in psychopathology has often been treated as a general hypo- or hyperresponsivity to reward, increasing data indicate that a comprehensive understanding of reward dysfunction requires characterization within more specific reward-processing domains, including subjective valuation, discounting, hedonics, reward anticipation and facilitation, and reinforcement learning. As such, more nuanced models of the nature of these abnormalities are needed. We describe several processing abnormalities capable of producing the types of selective alterations in reward-related behavior observed in different forms of psychopathology, including (mal)adaptive scaling and anchoring, dysfunctional weighting of reward and cost variables, competition between valuation systems, and reward prediction error signaling.
Somatomedins
Authors: Lawrence S. Phillips, Rena Vassilopoulou-Sellin
Journal: New England Journal of Medicine (1980)

IT is now over 20 years since Salmon and Daughaday hypothesized that stimulation of growth by growth hormone (somatotropin) was mediated by a circulating "sulfation factor."1 An understanding of this "factor" was hampered initially by technical problems with bioassay measurements, but recent improvements in methodology and advances in purification have led to increased interest in this area. It has become apparent that "sulfation factor" represents a family of circulating peptides, renamed somatomedins.2 These growth factors differ from other peptide hormones in three major ways: they appear to contribute to the same biologic actions; they appear to circulate bound to larger . . .
Effect of ranolazine administered after trastuzumab treatment on cardiotoxicity in mice.
Authors: Nicola Maurea, Carmela Coppola, Giovanna Piscopo, Francesca Galletta, Domenica Rea, Gennaro Riccio, Giovanna Lombardi, Alessandro Ottaiano, Claudio Arra, Claudia De Lorenzo, Rosario Vincenz Iaffaioli
Journal: Journal of Clinical Oncology (2015)

597 Background: Trastuzumab (T), a monoclonal antibody against ErbB2, has improved the prognosis of breast cancer patients, but ErbB2 blockade in cardiomyocytes can produce asymptomatic left ventricular dysfunction and heart failure, whose mechanism has not been elucidated and can include changes in Ca2+ regulation. We aim at assessing whether Ranolazine (R), an inhibitor of the late sodium current, administered after T treatment, blunts T cardiotoxicity in vivo and in vitro. Methods: In vitro, rat H9C2 cardiomyoblasts were treated with T (0.2µM) for 3 days and then treated in the absence or presence of R (1µM or 10μM) for 3 days. In vivo, fractional shortening (FS) and ejection fraction (EF) were measured by M-mode echocardiography and radial and longitudinal strain (RS and LS) were measured using 2D speckle-tracking, in C57/BL6 mice, at 0, 2 and after 7 days of daily administration of T (2.25 mg/kg/day). These measurements were repeated after 5 days of R treatment (305 mg/Kg/day) initiated at the end of T treatment. We have divided mice in 4 groups. The first group (G1) was treated with T for 7 days. The second group (G2) was treated with T for 7 days and then treated with R for 5 days. The other 2 were control groups: CG1 (sham) and CG2 (no R). We have evaluated tissue expression of BNP (brain natriuretic peptide) by PCR analysis on heart tissue. Results: R reduced T toxicity in H9C2 cardiomyoblasts as evidenced by higher percentage of viable cells treated with T+ R with respect to cells treated with T alone (p< 0.01). In vivo, after 7 days with T, FS decreased to 48.7 ± 4.1%, p< 0.01 vs 62.3 ± 0.8% (sham), EF to 81.8 ± 3.5%, p < 0.01 versus 91.7 ± 0.5% (sham), RS to 21 ± 8.1%, p < 0.01 versus 43.2 ± 4% (sham), and LS to -11 ± 3.7%, p < 0.01 versus -38.8 ± 6% (sham). In mice treated with R for 5 days after T treatment, the indices of cardiac function recovered: FS was 61 ± 1.2%, EF was 91 ± 0.7%, p < 0.01; RS was 35±1.8%, p < 0.05 versus T. However the alteration of LS persisted after treatment with R (-15.4 ± 5.1%, p = 0.3 vs. T). R prevents the increased expression of BNP (p < 0.05) on heart tissue Conclusions: R post-treatment blunts cardiotoxic effects due to T both in vitro and in vivo in a mouse model, as demonstrated by the normalization of the values of FS, EF and RS. LS is the first to impair and may be the last to recover.
Origin of the third heart sound.
Authors: E Craige, Y Ozawa, D Smith
Journal: BMJ (1969)

Origin of the Third Heart Sound For many years there has been speculation about the origin of the third heart sound.Some authors have held the theory that it is the sound of ventricular filling.'13Others have considered the sound to originate from the mitral valve, whether representing early closure of the valve4d or due to sudden tautening of the valve and its chordal attachments in early diastole.6Recently J. S. Fleming,8 in a study of mitral regurgitation before and after mitral valve replacement, produced evidence suggesting that the third heart sound in this condition may be due to sudden tautening of the valve in early diastole.Ultrasound measurements indicated that at the time of the sound the valve was in the half-open position, while the apex cardiogram showed abrupt checking of outward movement of the apex of the heart.He suggested that the latter is due to a suddent limitation of downward movement imposed by the tautened mitral valve with its chordal attachments.After excision of the mitral valve and replacement by a Starr- Edwards prosthesis the third sound disappeared, and apex cardiography no longer showed a checking movement in early diastole.This might support the theory that intact chordae tendineae are necessary for the production of the third heart sound.Disappearance of the sound might alternatively have resulted from the relief of mitral incompetence, with abolition both of the abnormally large left atrioventricular gradient in early diastole and of the increased stroke output of the left ventricle.Different combinations of factors in different conditions may contribute to the variable nature of the third heart sound.When the mitral valve is diseased from rheumatism and the chordae tendineae thickened and shortened, it seems possible that sudden tensing of the valve apparatus may be an important factor in the production of the third sound, which in this condition may be exceptionally loud and sharp in character.In severe aortic incompetence closure of the mitral valve in early-to-mid-diastole has been shown to occur,9-" and this may in part be responsible for a loud third sound
Intracellular Delivery: Diamond-Nanoneedle-Array-Facilitated Intracellular Delivery and the Potential Influence on Cell Physiology (Adv. Healthcare Mater. 10/2016)
Authors: Xiaoyue Zhu, Muk Fung Yuen, Li Yan, Zhenyu Zhang, Fujin Ai, Yang Yang, Peter K. N. Yu, Guangyu Zhu, Wenjun Zhang, Xianfeng Chen
Journal: Advanced Healthcare Materials (2016)

G. Zhu, W. Zhang, X. Chen, and co-workers show on page 1157 that diamond needle arrays can efficiently deliver biomolecules into living cells. The study paves the way to a wide application of the nanonneedle treatment by systematically investigating the influence of the treatment on metabolic signal pathways.
Imprinted Non-Coding RNA Genes, H19 and ZNF215, Are Potential Markers For Two-Year Survival For Acute Myeloid Leukemia Patients With Normal and Abnormal Karyotypes
Authors: Ming-Yu Yang, Jan-Gowth Chang, I-Ya Chen, Pai-Mei Lin, Hui-Hua Hsiao, Yi-Chang Liu, Wen-Chi Yang, Sheng-Fung Lin
Journal: Blood (2013)
172P Updated analysis: observational cohort study of 1st line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Comparison of infusional FU/oxaliplatin (OX) + BV and oral FU/OX + BV
Authors: Y. Komatsu, S. Yuki, H. Nakatsumi, K. Sawada, K. Hatanaka, T. Kato, T. Meguro, M. Nakamura, I. Iwanaga, M. Uebayashi, M. Tateyama, K. Eto, M. Kudo, K. Kato, H. Okuda, S. Sogabe, T. Miyagishima, K. Miyashita, N. Sakamoto, Y. Sakata
Journal: Annals of Oncology (2015)
New Agents in the Treatment of Chronic Myelogenous Leukemia
Authors: Javier Pinilla-Ibarz, Alfonso Quintás-Cardama
Journal: Journal of the National Comprehensive Cancer Network (2009)

The discovery of molecularly targeted agents that selectively inhibit bcr-abl tyrosine kinase activity, such as imatinib, has revolutionized the treatment and natural history of chronic myelogenous leukemia (CML). Treatment of chronic-phase CML with imatinib showed complete cytogenetic response rates of more than 40% in patients after failure of interferon-α, and more than 80% in patients with newly diagnosed CML. Patients with CML can now expect excellent long-term survival, often without major side effects. In most patients, however, residual leukemic burden remains detectable using a sensitive reverse transcription-polymerase chain reaction method. In addition, many patients undergoing imatinib therapy will either not respond or lose their response over time because of resistance or intolerance. The introduction of second-generation tyrosine kinase inhibitors (TKIs) re-establishes response in approximately half of these patients. Several agents are being developed for treating patients who experience suboptimal response to second-generation TKIs and for those who develop resistance caused by the emergence of highly resistant BCR-ABL1 mutations. This article provides an overview of novel targeted agents available for CML.
‘in Vivo Labelling Index System' in Myelomology Using an Innovative Thio-Thymidine PET/CT Combined with Amino-Acid PET/CT with Higher Visualizing Efficiency Than Conventional FDG PET/CT. - SUVmax by Thio-Thymidine PET/CT which Can Detect DNA-Synthesizing Myeloma Cell Nests in Vivo, Strongly Correlated with FISH Abnormalities in 74 Plasma Cell Dyscrasia Patients
Authors: Akiyoshi Miwa, Shotaro Hagiwara, Risen Hirai, Kazuo Kubota, Momoko Okazaki
Journal: Blood (2013)
Initial use of newer agents for advanced non-small cell lung cancer: Evidence from the National Cancer Institute Patterns of Care study.
Authors: B. L. Goulart, S. D. Ramsey
Journal: Journal of Clinical Oncology (2010)

6043 Background: Previous studies have reported on the patterns of use of first-line chemotherapy with platinum doublets in advanced NSCLC. There are no studies of patterns of use of newer agents in advanced NSCLC. We evaluated the frequencies and predictors of use of bevacizumab, erlotinib, and pemetrexed. Methods: We retrospectively selected patients with stage IIIB/IV NSCLC diagnosed in 2005 from a random sample drawn from SEER registries. We surveyed their treating physicians and reviewed outpatient and inpatient charts to abstract data on clinical and socio-demographic factors and types of anti-cancer drug regimens used for up to 2 years from diagnosis. We used descriptive statistics to report the frequency of use of new agents. We used multiple logistic regression to detect predictors of treatment with these new agents. Results: We analyzed 674 patients. The mean time of therapy verification was 22 months (SD ± 5 months) from diagnosis. Physicians responded the survey confirming chemotherapy regimens in 366 (54%) patients, SEER abstractors verified therapies in 300 (45%) patients, and in 8 (1%) patients either physicians or SEER abstractors verified the regimens. One-hundred (14.8%) patients received at least one new agent. Twenty-three (3.4%) patients received bevacizumab; 21 (3.1%) patients received pemetrexed; 68 (10.1%) patients received erlotinib, alone or in combination with other drugs at any time after the diagnosis up to 2 years. Off-label use of bevacizumab, pemetrexed, and erlotinib were 35%, 19%, and 58%, respectively. Predictors of use of any new agent included adenocarcinoma histology (OR = 2.06; p = 0.04); smoking status (OR = 0.22; p < 0.001); type of first-line regimen (platinum-taxane doublets: OR = 1.96; p = 0.04); PET-scan at diagnosis (OR = 2.34; p = 0.003); Midwest residency (OR = 2.34; p = 0.03). Conclusions: Overall early use of new agents was infrequent. Predictors of use of new agents suggest that oncologists follow published evidence or FDA recommendations for their use. Off-label use, however, remained substantial. As use of these agents increases, databases such as SEER-Medicare can track use in particular populations and link use with outcomes. No significant financial relationships to disclose.
THE FUNCTIONS OF THE SWEAT GLANDS
Authors: E Hesse
Journal: JAMA (1924)

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Case 27-1967
Authors: Conger Williams, Benjamin Castleman
Journal: New England Journal of Medicine (1967)

Presentation of Case First admission. A fifty-nine-year-old woman entered the hospital because of hemoptysis.She had been well until a year previously, when there was the onset of episodes of coughing productive of small amounts of blood. On examination rales were heard at the apex of the left lung. The heart was of normal size; a short Grade 2 systolic murmur was heard at the cardiac apex. The hemoglobin was 14.1 gm. per 100 ml.; the erythrocyte sedimentation rate was 42 mm. per hour. X-ray films of the chest showed a cardiothoracic ratio of 13:27; there were linear areas . . .