tbuckley/cabot-search huggingface dataset:
Cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in women more than 65 years old with advanced breast cancer: the elimination of age trends in toxicity by using doses based on creatinine clearance.
Authors: R S Gelman, S G Taylor
Journal: Journal of Clinical Oncology (1984)

Ninety-two patients with advanced breast carcinoma and no prior chemotherapy from 65 to 90 years old were treated with the combination cyclophosphamide (C), methotrexate (M), and 5-fluorouracil (F) (CMF). Because of the primary renal excretion of the first two drugs, their initial doses were calculated using a linear function of creatinine clearance. 5-Fluorouracil was given at 2/3 of the usual dose. These doses resulted in no significant age trends in almost all toxicity, response, time to failure, or cycle by cycle percentages of calculated dose actually received. There was significantly less nausea and vomiting as age increased (P less than .001) and patients greater than 80 years had a significantly shorter survival (P = .01) than patients aged 65 to 79 years. The toxicity results are in marked contrast to the experience of 126 patients aged 24 to 65 years treated with usual doses of CMF on earlier protocols. Among these younger patients there was a significant upward trend with age in diarrhea (P less than .001) and noticeable upward trends with age in hematologic toxicity (P = .06), infection (P = .06), and severe mucositis (P = .09). Patients greater than 65 years had their doses decreased less quickly than did patients less than 65 years; hence by the sixth cycle, the young and elderly patients were receiving almost the same amount of M and F.
Determination of the antidepressant effect of mirtazapine augmented with caffeine using Swiss-albino mice
Authors: Alexis Danielle Y. Co, Carlos Miguel Calderon, Andrea Tracy G. Cunanan, Kristin Almira B. De Guzman, Rosvielentine V. Rosales, Melchin Edreen O. Tapan, Deric S. Vengua, Gavino Ivan Tanodra
Journal: Asian Journal of Pharmaceutical Sciences (2015)
Ambulatory percutaneous lung biopsy with early discharge and Heimlich valve management of iatrogenic pneumothorax: more for less
Authors: A N Tavare, D D Creer, S Khan, R Vancheeswaran, S S Hare
Journal: Thorax (2015)

A prospective study of 489 consecutive outpatient image-guided percutaneous lung biopsies was conducted to determine whether early discharge, incorporating ambulatory Heimlich valve drain, is potentially advantageous to the National Health Service. Patients were discharged at 30 or 60 min, with significant pneumothoraces treated using Heimlich valve. 485 (99.2%) patients were successfully discharged early, 402 at 30 min. 87 (17.8%) patients developed pneumothorax: 52 required Heimlich valve; 5 proceeded to biopsy with Heimlich valve in situ. All drains were removed within 48 h, 38/52 (73.1%) at 24 h. Our results provide evidence for a paradigm shift in UK practice: early discharge lung biopsy, facilitated by ambulatory Heimlich valve, is safe with significant clinical and economic benefits.
Recent Advances in 21-Hydroxylase Deficiency
Authors: M I New, L S Levine
Journal: Annual Review of Medicine (1984)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Phase I and pharmacologic study of estramustine phosphate and short infusions of paclitaxel in women with solid tumors.
Authors: A A Garcia, S Keren-Rosenberg, D Parimoo, M Rogers, S Jeffers, R Koda, F M Muggia
Journal: Journal of Clinical Oncology (1998)

We sought to determine the tolerance of estramustine phosphate (EMP) combined with a 3-hour paclitaxel infusion in women with solid paclitaxel-pretreated solid tumors. Paclitaxel pharmacology was to be studied at the recommended phase II dose.Paclitaxel was administered to cohorts of at least three assessable patients at doses of 150, 180, 210, and 225 mg/m2, while EMP was given at 900 and 1,200 mg/m2/d in divided doses orally for 2 days preceding and on the day of paclitaxel. The pharmacologic study was performed at 225 mg/m2 paclitaxel given in the absence and 3 weeks later in the presence of EMP 900 mg/m2/d.Thirty-eight patients received a total of 178 courses. Grade 3 nausea, vomiting, and diarrhea were common at EMP 1,200 mg/m2 and paclitaxel 225 mg/ m2; this was considered the maximum-tolerated dose. Since these toxicities appeared related to EMP, the pharmacologic study used a dose of 900 mg/m2 of this agent with 225 mg/m2 paclitaxel. Antitumor activity was documented against breast and ovarian cancers at all levels. Paclitaxel pharmacokinetics without and with EMP did not differ.EMP 900 mg/m2 for 3 days and 225 mg/m2 paclitaxel by 3-hour infusion are well tolerated; antitumor activity was seen in women with paclitaxel-pretreated solid tumors. This apparent enhancement of antitumor effects is unlikely to be mediated by P-glycoprotein.
Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection
Authors: Aric L. Gregson, Aki Hoji, Patil Injean, Steven T. Poynter, Claudia Briones, Vyacheslav Palchevskiy, S. Sam Weigt, Michael Y. Shino, Ariss Derhovanessian, David Sayah, Rajan Saggar, David Ross, Abbas Ardehali, Joseph P. Lynch, John A. Belperio
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes.To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence.Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed.AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets.Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.
Detection of common dermatophytes in clinical specimens using a simple quantitative real-time TaqMan polymerase chain reaction assay
Authors: T. Ohst, C. Kupsch, Y. Gräser
Journal: British Journal of Dermatology (2015)

Dermatophytes are common fungal pathogens causing mostly superficial infections in humans with a high prevalence worldwide. Traditional detection techniques are time-consuming and insensitive, whereas molecular detection methods have proved to be much more rapid and sensitive.To develop a modular singleplex quantitative real-time polymerase chain reaction (qRT-PCR) assay for the detection of the most common dermatophytes in clinical specimens.The qRT-PCR assay is based on single-tube reactions with TaqMan probes. We validated the test with 311 clinical samples of human and animal origin submitted for routine diagnosis and compared the qRT-PCR results with microscopy and culture.qRT-PCR proved to be significantly more sensitive than microscopy and culture, with 21·2% more positive samples. Among the 201 dermatophytes identified 152 were Trichophyton rubrum (75·6%) and 34 were Trichophyton interdigitale (16·9%). Only 15 samples were determined as less common dermatophytes (Microsporum canis, Epidermophyton floccosum, Trichophyton verrucosum and Arthroderma benhamiae). In the present study, pathogen identification was achieved for 95·2% of all samples (including negatives) by applying only three detection tests (pan-dermatophyte, T. rubrum and T. interdigitale).The qRT-PCR assay developed in this study allows the specific and sensitive detection of relevant dermatophytes at low cost in a short time.
Quantitative real-time PCR assisted cell counting (qPACC) for epigenetic - based immune cell quantification in blood and tissue
Authors: Thomas Oliver Kleen, Jianda Yuan
Journal: Journal for ImmunoTherapy of Cancer (2015)

A novel form of immune cell quantification in blood and tissue is described using epigenetic - based, quantitative real-time PCR assisted cell counting (qPACC). The methylation status of the chromatin structure of either actively expressed or silenced genes is the basis of the epigenetic-based cell identification and quantification technology. Discovery of cell type specific removal of methyl groups (demethylation) from the 5'-carbon of the cytosine base in the dinucleotide cytosine phosphate guanine permits precise and robust quantification of immune cells from only small amounts of human blood or tissue samples. These epigenetic biomarkers located on genomic DNA are stably associated with a cell type of interest.
Choline and Human Nutrition
Authors: S H Zeisel, J K Blusztajn
Journal: Annual Review of Nutrition (1994)

Choline is crucial for sustaining life. It modulates the basic signaling processes within cells, is a structural element in membranes, and is vital during critical periods in brain development. Choline metabolism is closely interrelated with the metabolism of methionine and folate. We believe that the normal human diet provides sufficient choline to sustain healthy organ function. However, vulnerable populations may become choline deficient, including the growing infant, the pregnant or lactating woman, the cirrhotic, and the patient fed intravenously. Further studies of choline requirements in these groups are required.
Preparation of Engineered <i>Salmonella Typhimurium</i>‐Driven Hyaluronic‐Acid‐Based Microbeads with Both Chemotactic and Biological Targeting Towards Breast Cancer Cells for Enhanced Anticancer Therapy
Authors: Saji Uthaman, Shaohui Zheng, Jiwon Han, Young Jin Choi, Sunghoon Cho, Van Du Nguyen, Jong‐Oh Park, Seung‐Hwan Park, Jung‐Joon Min, Sukho Park, In‐Kyu Park
Journal: Advanced Healthcare Materials (2015)

In this study, a new type of targeted bacteriobots is prepared and investigated as a therapeutic strategy against solid tumors. Maleimide‐functionalized hyaluronic acid (HA) polymer is synthesized and cross‐linked with four‐arm‐thiolated polyethylene glycol (PEG‐SH) to form HA microbeads with diameter of 8 μm through the Michael‐type addition. Docetaxel (DTX)‐loaded nanoparticles are encapsulated in HA–PEG microbeads and sustained in vitro drug‐release pattern of the DTX from the HA–PEG microbeads is observed for up to 96 h. Dual‐targeted bacteriobots are prepared using CD 44 receptor‐targeted HA microbeads synthesized via microfluidics, followed by the attachment of the flagellar bacterium Salmonella typhimurium , which have been genetically engineered for tumor targeting, onto the surface of the HA microbeads by the specific interaction between streptavidin on the HA beads and biotin on the bacteria. After the attachment of bacteria, the bacteriobots show an average velocity of 0.72 μm s −1 and high chemotactic migration velocity of 0.43 μm s −1 towards 4T1 cells lysates. CD 44 receptor‐specific cellular uptake is verified through flow cytometry analysis and confocal imaging, demonstrating enhanced intracellular uptake in CD 44 receptor positive tumor cells compared to normal cells. Therefore, the present study suggests that these bacteriobots have dual‐tumor‐targeting abilities displaying their potential for targeted anticancer therapy.
P93 The complex process of risk assessment in liver transplantation: what do second opinions tell us?
Authors: A Gera, J O'Grady, M Al-Freah, M Heneghan, V Aluvihare, A Suddle, G Auzinger, A Prachalias, P Srinivasan, N Heaton, J Wendon, K Agarwal
Journal: Gut (2010)

Introduction  Liver transplant (LT) assessment involves a targeted evaluation of risk and benefit for any individual patient. In the context of limited organ supply, some patients with co-morbidities or marginal indications are declined on initial assessment. It is considered good practice to offer such patients a second opinion.  Aim  To assess the indications and outcomes in patients referred for a second opinion to our transplant programme.  Method  All patients who had been fully assessed and not accepted for LT in other units were identified. A retrospective review of patient notes and interrogation of a prospectively maintained database from December 2000 to May 2008 was performed. Baseline characteristics, indications for LT and 2-year survival were analysed.  Results  24 patients were referred from other institutions after having been declined listing. Reasons for initial decline ranged from cardiovascular risk in 8/24 (33.3%), HCV recurrence 2/24 (8.3%), HIV co-infection 2/24 (8.3%), technical suitability 2/24 (8.3%), substance misuse issues 2/24 (8.3%), other co-morbidities 5/25 (20.8%) and HCC on previous imaging felt to be beyond Milan criteria in 3/24 (12.5%). All underwent full reassessment and multidisciplinary review.  Median age was 59 years (IQR 52–68 years), median MELD and UKELD at time of assessment were 17 (12–19) and 55 (51–60) respectively. 15/24 (63%) were male. Overall 16/24 (67%) were ultimately accepted for transplantation. For those again declined for transplantation, the reasons were confirmatory to those outlined at the referring hospital. Of those listed for LT 9/16 (56%) received a graft, 6 received cadaveric whole grafts, 3 received right lobe grafts (1 from a live donor, 1 non heart beating, 1 cadaveric split).  In those who received a transplant 1-year survival was 100%, 2-year survival 89%. Mortality on the waiting list was 31% (5/16) with 1 patient currently awaiting LT, 1 patient was subsequently transplanted back at their original transplant centre. Those who died on the waiting list had higher median age, MELD scores, UKELD scores and were more likely to be blood group O (4/5, 80%). However these were not statistically significant. The median length of stay post LT was higher in the group referred for a second opinion and then transplanted (29 days, IQR 21–55) as compared to our standard population (22 days, IQR 15–40).  Conclusion  Patients meeting guidelines for LT should be listed according to need. Our series demonstrates that a second opinion for LT can be beneficial for selected individual patients. Outcomes in selected cases can be optimal, although these patients theoretically represent higher operative risk. Mortality was associated with waiting times and blood group. These data support the utility of the second opinion component of the transplant assessment process.
Mosquito salivary allergen Aed a 3: cloning, comprehensive molecular analysis, and clinical evaluation
Authors: Z. Peng, W. W. Xu, Y. Sham, H. Lam, D. Sun, L. Cheng, N. F. Rasic, Q. Guan, A. A. James, F. E. R. Simons
Journal: Allergy (2015)

Background Allergic reactions to mosquito bites are an increasing clinical concern. Due to the lack of availability of mosquito salivary allergens, they are underdiagnosed. Here, we reported a newly cloned mosquito Aedes (Ae.) aegypti salivary allergen. Methods A cDNA encoding a 30-kDa Ae. aegypti salivary protein, designated Aed a 3, was isolated from an expression library. The full-length cDNA was cloned into a baculovirus expression vector, and recombinant Aed a 3 (rAed a 3) was expressed, purified, and characterized. Skin prick tests with purified rAed a 3 and Ae. aegypti bite tests were performed in 43 volunteers. Serum rAed a 3-specific IgE levels were measured in 28 volunteers. Results The primary nucleotide sequence, deduced amino acid sequence, and IgE-binding sites of Aed a 3 were identified. rAed a 3-selected antibodies recognized a 30-kDa Ae. aegypti saliva protein. rAed a 3 bound IgE in mosquito-allergic volunteers and the binding could be inhibited by the addition of natural mosquito extract dose dependently. Immediate skin test reactions to rAed a 3 correlated significantly with mosquito bite-induced reactions. Of the bite test-positive volunteers, 32% had a positive rAed a 3 skin test and 46% had specific IgE. No bite test-negative volunteers reacted to rAed a 3 in either the skin tests or the IgE assays, confirming the specificity of the assay. Conclusions Aed a 3 that corresponds to the Aegyptin protein is a major mosquito salivary allergen. Its recombinant form has biological activity and is suitable for use in skin tests and specific IgE assays in mosquito-allergic individuals.
Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer.
Authors: L H Einhorn, P J Loehrer, S D Williams, S Meyers, T Gabrys, S R Nattan, R Woodburn, R Drasga, J Songer, W Fisher
Journal: Journal of Clinical Oncology (1986)

In this phase III randomized study, 124 evaluable patients with unresectable non-small-cell lung cancer (NSCLC) were randomized to vindesine v cisplatin (120 mg/m2) plus vindesine v cisplatin (60 mg/m2) plus vindesine plus mitomycin C. The objective response rate for cisplatin and vindesine was 27% v 20% for cisplatin, vindesine, and mitomycin C, and 14% for vindesine alone (P = .25 for cisplatin and vindesine v vindesine). The percentage of patients having stable disease (no progression for a minimum of 3 months) was 20% (cisplatin and vindesine), 27% (cisplatin, vindesine, and mitomycin C), and 26% (vindesine alone), respectively. The median survival time for vindesine was 18 weeks, compared with 26 weeks for cisplatin and vindesine and 17 weeks for cisplatin, vindesine, and mitomycin C. Overall survival was not statistically different for cisplatin plus vindesine v vindesine (P = .65). There was no evidence for improved duration of remission or survival of responders with the cisplatin (120 mg/m2) and vindesine arm. This study failed to demonstrate sufficient therapeutic benefit for cisplatin and vindesine (+/- mitomycin C) compared with single-agent vindesine to justify the increased cost and toxicity of these combination regimens.
<i>The Space Between Us</i>: Evaluating a multi-user affective brain-computer music interface
Authors: Joel Eaton, Duncan Williams, Eduardo Miranda
Journal: Brain-Computer Interfaces (2015)

Music as a mechanism for neuro-feedback presents an interesting medium for artistic exploration, especially with regard to passive BCI control. Passive control in a brain-computer music interface (BCMI) provides a means for approximating mental states that can be mapped to select musical phrases, creating a system for real-time musical neuro-feedback. This article presents a BCMI for measuring the affective states of two users, a performer and an audience member, during a live musical performance of the piece titled The Space Between Us. The system adapts to the affective states of the users and selects sequences of a pre-composed musical score. By affect-matching music to mood and subsequently plotting affective musical trajectories across a two-dimensional model of affect, the system attempts to measure the affective interactions of the users, derived from arousal and valence recorded in EEG. An Affective Jukebox, the work of a previous study, validates the method used to read emotions across two dimensions in EEG in response to music. Results from a live performance of The Space Between Us indicate that measures of arousal may be manipulated by emotionally charged music, and that measures of valence are less responsive to musical stimuli, across both users. As such, an affective BCMI presents a novel platform for designing individualized musical performance and composition tools where the selection of music can reflect and induce affect in users. Furthermore, an affective channel of communication shows potential for enhancing collaboration in music-making in a wider context, for example in the roles of therapist and patient.
Postoperative radiation therapy for epithelial ovarian cancer: the curative role based on a 24-year experience.
Authors: A Martinez, M F Schray, A E Howes, M A Bagshaw
Journal: Journal of Clinical Oncology (1985)

We updated 152 cases of epithelial ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) stages I through III, treated at the Stanford Medical Center (Stanford, Calif) with irradiation as the only postoperative therapy. In 133 patients, radiation was directed only to those regions of known disease, while it was delivered to the whole abdomen and pelvis by the Martinez technique in 19 patients. Mean follow-up time was 6.8 years. The results were analyzed as freedom from relapse (FFR) at 15 years; overall, FFR constituted 44% of the patients. Statistically significant differences of FFR appeared between stages II (60%) and III (16%); among the histopathologic variants endometrioid (64%), serous papillary (45%), and undifferentiated (7%); between pathologic grades 2 (68%) and 3 (20%); between amounts of postoperative residual disease less than 2 cm (48%) and greater than 2 cm (16%); and between ages less than 40 (80%) and greater than or equal to 40 (38%). Considering all stages and grades together, FFR in the 54 cases with unfavorable residuum (greater than 2 cm) was 14%. Among the 98 with favorable residuum (none, or less than 2 cm) FFR was 62%; and 14 (39%) of the 36 relapses were in the untreated upper abdomen. Results in the favorable group support effectiveness of irradiation as postoperative therapy. These patterns of relapse suggest that whole-abdominopelvic irradiation would further increase FFR. We believe that, for favorable disease as defined such radiotherapy should be the standard for comparison.
Identification of a predictive efficacy signature from microarray analysis of human tumor xenografts treated with anticancer compounds.
Authors: David K. Bol, Zoe Weaver, Qin Zong, Jeffrey W. Stovel, Paul E. Young, Stephen J. Garvey, Tracy Perry, Yvonne Knight, Derong Liu, Pachai Natarajan, Jeffrey R. Bullard, Stanislaw Pikul, Janak Padia, Sean O’Brien, Jiemin Lu
Journal: Cancer Research (2004)

2017   How therapeutic compounds affect tumors is a complex, dynamic process. Ultimately, all of the effects, whether on the tumor cell, the vasculature, or other stromal cells, are reflected in changes in gene expression in the tumor. Using this basic premise, we have devised a system where we rapidly assess the effects of compounds in an in vivo setting to determine multiple pharmacodynamic parameters simultaneously. By treating tumor-bearing mice with known and experimental anticancer compounds, we are able to see how compounds impact the tumor in the animal, accounting for protein binding, pharmacokinetics, tissue penetration, toxicity, and on-target effects. Using multiple compounds that work by a variety of mechanisms, we have been able to develop a consensus ‘signature’ that correlates the gene expression signature from a single effective dose with antitumor efficacy following a multiple dose regimen. Furthermore, we have built a predictive model using gene expression changes to evaluate multiple compounds in a lead optimization series to predict which compounds will be active in a given model. Finally, by analyzing multiple xenograft models, we have been able to identify pathways that are affected when a model is responsive compared to models that are not responsive to the same set of compounds. It should be clear from this presentation that this type of work during the lead optimization phase of drug discovery establishes a genetic basis for identifying sensitive patient populations, and the biologic markers to detect a response.