tbuckley/cabot-search huggingface dataset:
Impact of hydroxyurea on clinical events in the BABY HUG trial
Authors: Courtney D. Thornburg, Beatrice A. Files, Zhaoyu Luo, Scott T. Miller, Ram Kalpatthi, Rathi Iyer, Phillip Seaman, Jeffrey Lebensburger, Ofelia Alvarez, Bruce Thompson, Russell E. Ware, Winfred C. Wang
Journal: Blood (2012)
Nationwide Longitudinal Study of Psychological Responses to September 11
Authors: Roxane Cohen Silver
Journal: JAMA (2002)

OST PEOPLE ENCOUNTER stressful events that can alter the course of their lives.Clinicians often see the mental and physical health consequences of such events. 1On September 11, 2001, everyone in the United States was exposed to an incident unprecedented in scope and traumatic impact.Tens of thousands of people directly witnessed the terrorist attacks against the World Trade Center (WTC) and the Pentagon; others viewed the attacks and their aftermath via the media-most within half an hour after they occurred. 2It has been argued that this national trauma "influenced and will continue to influence the clinical presentation of patients seeking health care services" across the country 3 and that it offers "an unfortunate opportunity to find out more about what something like this does to a country as a whole." 4 Research after the Oklahoma City, Okla, bombing suggests that emotional responses to a terrorist attack can be highly variable. 57][8] Yet, information about the range and rates of distress to be expected following such a national trauma is limited.Unfortunately, potentially harmful myths about coping remain prevalent in lay and professional communities, 8 such as the ex-pectation that subjective responses to trauma are proportional to the degree of objective loss experienced.Gaining information concerning the adjustment process can aid clinicians by iden-tifying risk factors 9,10 and can inform the design of interventions for individuals coping with stressful life events. 11e conducted a longitudinal study of acute responses to the terrorist attacks
Side Effects during Immunotherapy with Purified Grass Pollen Extracts
Authors: Ole ØSterballe
Journal: Allergy (1982)

In a 3‐year prospective double blind study, grass pollen allergic patients were allocated to perennial hyposensitization with the timothy major allergens Nos. 19 and 25 (2‐component extract) or a 20‐component timothy extract. The extracts were biologically standardized and adsorbed to aluminium hydroxide for treatment. Systemic side effects (SSE) had début after 1 1/2–5 h and lasted without treatment 1/2–10 h. Treatment with the 2‐component extract showed preponderance of minor SSE (arthralgia, rhinitis, tiredness, headache, conjunctivitis, nausea, flu‐like symptoms), but major SSE (urticaria, angioedetma, asthma) were equally distributed between treatment with the two timothy extracts. Major SSE comiplicated the treatment before the first grass pollen season in 33% of the patients vs. only in 3% during the subsequent perentiial therapy, and developed (92%) at high single dose of ≥1,000 biological units. The majority (69%) were later able to reach the same or higher dose without relapse. Most (62%) patients with major SSE were predicted by high nasal sensitivity before treatment. Only 18% of the patients had immediate local skin reactions of ≥2 cm, but delayed local side effects of ≥10 cm were recorded in 70%. Immediate skin reactions did not correlate with delayed skin reactions or with SSE, but delayed local side effects tended towards negative correlation with major SSE. A mean area reduction of 50% of the delayed skin reactions was recorded by repetition of a single dose. Subcutaneous nodules appeared at single doses of ≥5,000 biological units. Only 5% of the patients contracted nodules during initial preseasonal therapy compared with 38% during subsequent perennial dosage. The nodules contained typical benign granulomas, and the frequency in the two groups was proporitonate to the quantity of aluminium in the two extracts.
Cloning, expression, and functional characterization of the von Willebrand factor–cleaving protease (ADAMTS13)
Authors: Barbara Plaimauer, Klaus Zimmermann, Dirk Völkel, Gerhard Antoine, Randolf Kerschbaumer, Pegah Jenab, Miha Furlan, Helen Gerritsen, Bernhard Lämmle, Hans Peter Schwarz, Friedrich Scheiflinger
Journal: Blood (2002)
The role of PEEP in patients with chronic obstructive pulmonary disease during assisted ventilation
Authors: A Rossi, R Brandolese, J Milic-Emili, SB Gottfried
Journal: European Respiratory Journal (1990)

In patients with acute respiratory failure (ARF) due to acute exacerbation of chronic obstructive pulmonary disease (COPD), the intrinsic positive end-expiratory pressure (PEEPi) can significantly increase workload for ventilation. It has been suggested that, in the presence of expiratory flow limitation, application of low levels of PEEP by the ventilator can be used to reduce PEEPi and therefore the magnitude of the inspiratory effort during assisted mechanical ventilation (or pressure support) and weaning. Clearly, pulmonary hyperinflation should not be further enhanced in order not to counteract the beneficial effect of removing PEEPi by decreasing respiratory muscle length and force. This use of PEEP in COPD patients is supported not only by theory, but also by recent experimental work, although sufficient clinical information is not yet available to provide a guideline for titration of the PEEP level. Therefore, application of PEEP in COPD patients requires close monitoring of the end-expiratory lung volume. This can be accomplished, among other noninvasive ways (e.g. the inductive plethysmography), by inspection of flow/volume curves during application of increasing levels of PEEP. The shape of the expiratory limb of the flow/volume curve can also suggest the presence of dynamic hyperinflation and expiratory flow limitation.
Laser Treatment of Traumatic Scars With an Emphasis on Ablative Fractional Laser Resurfacing
Authors: R. Rox Anderson, Matthias B. Donelan, Chad Hivnor, Eric Greeson, E. Victor Ross, Peter R. Shumaker, Nathan S. Uebelhoer, Jill S. Waibel
Journal: JAMA Dermatology (2013)

Despite expert wound care and assiduous management with traditional therapy, poor cosmetic outcomes, restricted motion, and symptoms such as pain and itch are a pervasive problem of disfiguring and debilitating scars. The advent of ablative fractional photothermolysis within the past decade and its application to the treatment of traumatic scars represents a breakthrough in the restoration of function and cosmetic appearance for injured patients, but the procedure is not widely used.To provide a synthesis of our current clinical experience and available literature regarding the laser treatment of traumatic scars with an emphasis on fractional resurfacing.Eight independent, self-selected academic and military dermatology and plastic surgery physicians with extensive experience in the use of lasers for scar treatment assembled for a 2-day ad hoc meeting on January 19 and 20, 2012. Consensus was based largely on expert opinion, but relevant literature was cited where it exists.After consensus was appraised, we drafted the manuscript in sections during the course of several months. The draft was then circulated among all panel members for final review and comment. Our consensus is that laser treatment, particularly ablative fractional resurfacing, deserves a prominent role in future scar treatment paradigms, with the possible inclusion of early intervention for contracture avoidance and assistance with wound healing.Laser scar therapy, particularly fractional ablative laser resurfacing, represents a promising and vastly underused tool in the multidisciplinary treatment of traumatic scars. Changes to existing scar treatment paradigms should include extensive integration of fractional resurfacing and other combination therapies guided by future research.
Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma
Authors: Thomas E. Witzig, Susan M. Geyer, Irene Ghobrial, David J. Inwards, Rafael Fonseca, Paul Kurtin, Stephen M. Ansell, Ronnie Luyun, Patrick J. Flynn, Roscoe F. Morton, Shaker R. Dakhil, Howard Gross, Scott H. Kaufmann
Journal: Journal of Clinical Oncology (2005)

Mantle cell lymphoma (MCL) is characterized by a t(11;14) resulting in overexpression of cyclin D1 messenger RNA. This study tested whether temsirolimus (previously known as CCI-779), an inhibitor of the mammalian target of rapamycin kinase that regulates cyclin D1 translation, could produce tumor responses in patients with MCL.Patients with relapsed or refractory MCL were eligible to receive temsirolimus 250 mg intravenously every week as a single agent. Patients with a tumor response after six cycles were eligible to continue drug for a total of 12 cycles or two cycles after complete remission, and were then observed without maintenance.Thirty-five patients were enrolled and were assessable for toxicity; one patient had MCL by histology but was cyclin D1 negative and was ineligible for efficacy. The median age was 70 years (range, 38 to 89 years), 91% were stage 4, and 69% had two or more extranodal sites. Patients had received a median of three prior therapies (range, one to 11), and 54% were refractory to the last treatment. The overall response rate was 38% (13 of 34 patients; 90% CI, 24% to 54%) with one complete response (3%) and 12 partial responses (35%). The median time-to-progression in all patients was 6.5 months (95% CI, 2.9 to 8.3 months), and the duration of response for the 13 responders was 6.9 months (95% CI, 5.2 to 12.4 months). Hematologic toxicities were the most common, with 71% (25 of 35 patients) having grade 3 and 11% (four of 35 patients) having grade 4 toxicities observed. Thrombocytopenia was the most frequent cause of dose reductions but was of short duration, typically resolving within 1 week.Single-agent temsirolimus has substantial antitumor activity in relapsed MCL. This study demonstrates that agents that selectively target cellular pathways dysregulated in MCL cells can produce therapeutic benefit. Further studies of this agent in MCL and other lymphoid malignancies are warranted.
Impact of Insulin-Like Growth Factor Type 1 Receptor, Epidermal Growth Factor Receptor, and HER2 Expressions on Outcomes of Patients with Gastric Cancer
Authors: Junichi Matsubara, Yasuhide Yamada, Yoshinori Hirashima, Daisuke Takahari, Natsuko T. Okita, Ken Kato, Tetsuya Hamaguchi, Kuniaki Shirao, Yasuhiro Shimada, Tadakazu Shimoda
Journal: Clinical Cancer Research (2008)

Expression levels of insulin-like growth factor type 1 receptor (IGF-IR), epidermal growth factor receptor (EGFR), and HER2 expressions have been linked to clinical outcomes in several solid tumors. However, the clinical significance of these biomarkers in gastric cancer (GC) remains unclear. This study was designed to delineate the clinical implications of these three biomarkers in GC.The study group comprised 87 patients who underwent gastrectomy at National Cancer Center Hospital and subsequently received chemotherapy for recurrent or residual tumors. Using immunohistochemical techniques, we analyzed the expressions of IGF-IR, EGFR, and HER2 on formalin-fixed paraffin-embedded specimens of surgically removed primary tumors.IGF-IR expression (defined as >10% membranous staining) was found in 67 tumors (77%), EGFR expression in 55 (63%), and HER2 expression in 16 (18%). Positive coexpression of IGF-IR and EGFR was found in 48 tumors (55%), that of IGF-IR and HER2 in 16 (18%), and that of EGFR and HER2 in 13 (15%). Multivariate survival analysis showed that IGF-IR-positive expression [hazard ratio (HR) 2.14, 95% confidence interval (95% CI) 1.20-3.82; P = 0.01], performance status 1 or 2 (HR 1.83, 95% CI 1.15-2.91; P = 0.01), and diffuse type tumors (HR 1.71; 95% CI 1.08-2.70; P = 0.02) were significant predictors of poor survival.IGF-IR expression in surgical GC specimens, poor performance status, and diffuse type tumors are significant predictors of poor outcomes in patients with GC. Our data suggest that anti-IGF-IR strategies may prove valuable in such patients.
Comorbidity, Impairment, and Suicidality in Subthreshold PTSD
Authors: Randall D. Marshall, Mark Olfson, Fredric Hellman, Carlos Blanco, Mary Guardino, Elmer L. Struening
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Reliance on the categorical model of psychiatric disorders has led to neglected study of posttraumatic sequelae that fall short of full criteria for posttraumatic stress disorder (PTSD). Substantial disability and suicidal risk is associated with subthreshold PTSD, but this association has not been well studied. In addition, no studies have examined the role of comorbidity in explaining disability and impairment in subthreshold PTSD. METHOD: On National Anxiety Disorders Screening Day 1997, 2,608 out of 9,358 individuals screened for affective and anxiety disorders at 1,521 sites across the United States reported at least one PTSD symptom of at least 1 month’s duration. Impairment, comorbid anxiety disorders, major depressive disorder, and rates of suicidality were determined and compared for individuals with no, one, two, three, or four (full PTSD) symptoms on a screening questionnaire. Regression analyses examined the relative contribution of subthreshold PTSD and comorbid disorders to impairment and suicidal ideation. RESULTS: Impairment, number of comorbid disorders, rates of comorbid major depressive disorder, and current suicidal ideation increased linearly and significantly with each increasing number of subthreshold PTSD symptoms. Individuals with subthreshold PTSD were at greater risk for suicidal ideation even after the authors controlled for the presence of comorbid major depressive disorder. CONCLUSIONS: Higher numbers of subthreshold PTSD symptoms were associated with greater impairment, comorbidity, and suicidal ideation. Disability and impairment found in previous studies of subthreshold PTSD symptoms may be related in part to the presence of comorbid disorders. However, the presence of subthreshold PTSD symptoms significantly raised the risk for suicidal ideation even after the authors controlled for major depressive disorder. Given the broad public health implications of these findings, more efforts are needed to identify subthreshold PTSD symptoms in clinical populations, epidemiologic surveys, and treatment studies.
Geographical distribution of gastrointestinal cancers in India with special reference to causation.
Authors: S L Malhotra
Journal: Gut (1967)

EDITORIAL COMMENT These important observations suggest that is it the irritation from the highly alkaline lime, and not the tobacco leaf, on the betel nut in the chewing quid, which predisposes towards malignant changes in the buccal mucosa.Interesting studies on the distribution of cancer of the stomach and cancer of the liver are recorded and it is suggested that these differences may possibly be associated with variations in the pattern of diet and eating.
Multifunctional Upconversion-Magnetic Hybrid Nanostructured Materials: Synthesis and Bioapplications
Authors: Xiaomin Li, Dongyuan Zhao, Fan Zhang
Journal: Theranostics (2013)

The combination of nanotechnology and biology has developed into an emerging research area: nano-biotechnology.Upconversion nanoparticles (UCNPs) have attracted a great deal of attention in bioapplications due to their high chemical stability, low toxicity, and high signal-to-noise ratio.Magnetic nanoparticles (MNPs) are also well-established nanomaterials that offer controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging (MRI).As a result, these nanoparticles could have many applications in biology and medicine, including protein purification, drug delivery, and medical imaging.Because of the potential benefits of multimodal functionality in biomedical applications, researchers would like to design and fabricate multifunctional upconversion-magnetic hybrid nanostructured materials.The hybrid nanostructures, which combine UCNPs with MNPs, exhibit upconversion fluorescence alongside superparamagnetism property.Such structures could provide a platform for enhanced bioimaging and controlled drug delivery.We expect that the combination of unique structural characteristics and integrated functions of multifunctional upconversion-magnetic nanoparticles will attract increasing research interest and could lead to new opportunities in nano-bioapplications.
Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47 <sup> <i>phox</i> </sup> Gene Expression in Response to Angiotensin II
Authors: Weihua Ni, Yumei Zhan, Huamei He, Elizabeth Maynard, James A. Balschi, Peter Oettgen
Journal: Circulation Research (2007)

Angiotensin (Ang) II is a potent mediator of vascular inflammation. A central mechanism by which Ang II promotes inflammation is through the generation of reactive oxygen species (ROS). In the current study, we investigated the role of the transcription factor Ets-1 in regulating Ang II–induced ROS generation. ROS generation was measured in the thoracic aorta of Ets-1 −/− mice compared with littermate controls after continuous infusion of Ang II. H 2 O 2 and superoxide anion (O 2 − ) production were significantly blunted in the Ets-1 −/− mice. Inhibition of Ets-1 expression by small interfering RNA in primary human aortic smooth muscle cells also potently inhibited ROS production and the induction of the NAD(P)H oxidase subunit p47 phox in response to Ang II. To evaluate the therapeutic potential of inhibiting Ets-1 in wild-type mice, dominant negative Ets-1 membrane-permeable peptides were administered systemically. Ang II–induced ROS production and medial hypertrophy in the thoracic aorta were markedly diminished as a result of blocking Ets-1. In summary, Ets-1 functions as a critical downstream transcriptional mediator of Ang II ROS generation by regulating the expression of NAD(P)H oxidase subunits such as p47 phox .
RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform
Authors: C. Frank Bennett, Eric E. Swayze
Journal: The Annual Review of Pharmacology and Toxicology (2010)

Dramatic advances in understanding of the roles RNA plays in normal health and disease have greatly expanded over the past 10 years and have made it clear that scientists are only beginning to comprehend the biology of RNAs. It is likely that RNA will become an increasingly important target for therapeutic intervention; therefore, it is important to develop strategies for therapeutically modulating RNA function. Antisense oligonucleotides are perhaps the most direct therapeutic strategy to approach RNA. Antisense oligonucleotides are designed to bind to the target RNA by well-characterized Watson-Crick base pairing, and once bound to the target RNA, modulate its function through a variety of postbinding events. This review focuses on the molecular mechanisms by which antisense oligonucleotides can be designed to modulate RNA function in mammalian cells and how synthetic oligonucleotides behave in the body.
Strategies to prevent unintended pregnancy: increasing use of long-acting reversible contraception
Authors: P.D. Blumenthal, A. Voedisch, K. Gemzell-Danielsson
Journal: Human Reproduction Update (2010)

Despite increasing contraceptive availability, unintended pregnancy remains a global problem, representing as many as 30% of all known pregnancies. Various strategies have been proposed to reverse this disturbing trend, especially increased use of long-acting reversible contraceptive (LARC) methods. In this review we aim to discuss the role of LARC methods and importance of contraceptive counseling in reducing unintended pregnancy rates. References/resources cited were identified based on searches of medical literature (MEDLINE, 1990–2009), bibliographies of relevant publications and the Internet. LARC methods—copper intrauterine devices (IUDs), progestogen-releasing intrauterine system and injectable and implantable contraceptives—are safe and effective contraceptive options (unintended pregnancy rates with typical versus perfect use: 0.05–3.0 versus 0.05–0.6%) that are appropriate for a wide range of women seeking to limit or space childbearing. Despite their safety and efficacy records, these methods remain underutilized; injectable and implantable methods are used by an estimated 3.4% and intrauterine methods by 15.5% of women worldwide. LARC methods require no daily or coital adherence and avoid the adverse events and health risks of estrogen-containing contraceptives. The copper IUD and progestin-only injections and implants have been shown to be more cost-effective than more commonly used methods, such as condoms and the pill (5-year savings: $13 373–$14 122, LARC; $12 239, condoms; $12 879, pill). Women who are considering use of LARC methods should receive comprehensive contraceptive counseling, as women who receive counseling before use demonstrate higher rates of after-use method satisfaction, continuation and acceptance than those who do not.
GRIM-19 expression and its correlation with clinical outcomes of an induction chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: X. Zhang, M. S. Choe, J. E. Lee, S. Muller, M. Tighiouart, A. Rogatko, B. S. Glisson, Z. Chen, F. R. Khuri, D. M. Shin
Journal: Journal of Clinical Oncology (2005)

5519 Background: GRIM-19 is a novel gene associated with retinoid-interferon induced mortality (GRIM). The expression and function of GRIM-19 in SCCHN have not been reported to date. This study examined the expression of this gene and correlated it with the treatment outcomes in patients with locally advanced SCCHN. Methods: Thirty-nine baseline tumor tissues were collected from 54 patients who entered in a phase II study of induction chemotherapy with Paclitaxel, Ifosfamide, and Carboplatin (TIC) for locally advanced SCCHN. Immunohistochemistry analysis was performed for GRIM-19 expression using paraffin-embedded tumor specimens collected before the treatment. Weight index [WI = % Positive Staining (> 0) in tumor × Intensity Score, 0 - 300] was used for quantifying expression levels. Correlations between GRIM-19 expression and clinical characteristics were also evaluated. Results: The characteristics of the 39 patients are: median age: 58 years old; male 33/female 6; stage III 6/IV 33; tumor sites (Oral cavity 3, Oropharynx 21, Hypopharynx 5, Larynx 8, Others 2); differentiation (Grade I 7/ II 16/III16). With TIC chemotherapy for 3–4 cycles, 32/39 achieved CR/PR, and 7/39 had no change (NC) or progressive disease (PD). The positive staining of GRIM-19 was localized in both the cytoplasm and nuclei of the cancer cells. Ninety five percent of tumor samples (37/39) showed positive staining of GRIM-19 (WI/samples: 0/2; ∼ 100/12; ∼ 200/5; ∼300/20). The median value of GRIM-19 expression in the CR/PR group (WI: 187.5) was significantly lower than that in the NC/PD group (WI: 300) (p = 0.047). With a median follow-up of 56.9 months, the median survival of the low GRIM-19 expression group (WI ≤ 200, n = 19) has not been reached, while the median survival of the high GRIM-19 expression group (WI > 200, n = 20) was 39.9 months (p = 0.057). Conclusions: High expression of GRIM-19 correlated with poor clinical response and worsened survival for the TIC chemotherapy treatment in patients with locally advanced SCCHN. Therefore, it may serve as a good biomarker and deserves to be incorporated into future clinical trails. (Supported in part by 2RO1 CA75603 to D.M.S.). No significant financial relationships to disclose.