tbuckley/cabot-search huggingface dataset:
Intramedullary spinal cord metastases from small cell carcinoma of the lung.
Authors: K C Murphy, R Feld, W K Evans, F A Shepherd, R Perrin, A A Sima, P Y Poon
Journal: Journal of Clinical Oncology (1983)

Four patients with intramedullary spinal cord metastases from small cell carcinoma of the lung (SCCL) are described, with emphasis on clinical presentation and treatment. All patients developed the Brown-Séquard syndrome due to intramedullary tumor in the cervical spinal cord, three within 2 mo after combined modality treatment using chemotherapy and radiotherapy. One patient presented with a Brown-Séquard syndrome and an extradural spinal cord compression from tumor. The radiological and cerebrospinal fluid findings are presented and discussed. Radiation treatment was administered to the involved segments of spinal cord in each patient. All patients responded; two for 3 and 7 mo, two for 3 and 4 wk, respectively. There was significant improvement in the quality of life for three of the four patients.
Amoxycillin/clavulanate resistance as related to β-lactamase content in Escherichia coli strains from community-acquired urinary tract infections in Greece
Authors: Leonidas S. Tzouvelekis, Eva Tzelepi, Antonios Maniatis, Evangelos Vogiatzakis, Olga Paniara, Yiannis Tselentis, Nicholas J. Legakis
Journal: Clinical Microbiology and Infection (1998)
Total Dose Iron Dextran Infusion in Cancer Patients: Is it SaFe<sup>2+</sup>?
Authors: Jeffrey A. Gilreath, David D. Stenehjem, George M. Rodgers
Journal: Journal of the National Comprehensive Cancer Network (2012)

The feasibility of the large, single-dose intravenous iron repletion method, which is known today as total dose infusion (TDI), has been demonstrated over decades. However, this method of iron repletion was chiefly developed for patients with large iron deficits, such as those with pregnancy-induced anemia, chronic bleeding disorders, and absolute iron-deficiency anemia (serum ferritin < 30 ng/mL, transferrin saturation < 15%) who were unable to receive frequent small doses of intravenous iron. Today, 50 years after the advent of TDI, more is known about iron metabolism and storage, but the optimal dosing strategy for intravenous iron in patients with cancer is still not well defined. The proinflammatory state of cancer, or its treatment, may influence the response to intravenous iron therapy. Additionally, the long-term adverse effects of large single doses or smaller more frequent doses have yet to be studied in the oncology population. Historically, safety concerns surrounding the administration of intravenous iron have centered on anaphylaxis. Newer concerns are being raised, such as oxidative stress, iron overload, venous thromboembolism, infection risk, and tumor growth. Therefore, with the original premise of TDI assuming low levels of inflammation, coupled with the recent data surrounding the adverse effects of blood transfusions and erythropoietic-stimulating agents, this article reviews the risks and benefits of TDI administration specifically for patients with cancer.
Analysis of activation process of dyspnea sensation in CNS in patients with COPD measured by fMRI
Authors: Masachika Akiyama, Jun Suzuki, Yutaka Nakamura, Hitoshi Kobayashi, Kohei Yamauchi, Ikuko Uwano, Yutaka Matsumura, Makoto Sasaki
Journal: European Respiratory Journal (2011)

Introduction:  Dyspnea is the cardinal symptom of COPD. Localization of dyspnea sensation in the brain has been studied by a small number of investigators. However little is known about transmission and activation of dyspnea sensation in CNS.   Objectives:  We analyzed pathway and localization of dyspnea sensation in the brain of normal subjects and COPD patients using functional magnetic resonance imaging (fMRI).   Methods:  Six normal subjects (M/F; 5/1, 53.7±5.9 yr: mean ± SEM) and 4 COPD patients (M/F; 4/0, 68.5±1.7 yr) were recruited. After informed consent, these subjects were requested to breathe through resistive loads ranging from 5 to 50 cm H2O/L/sec adjusted by the Borg CR10 Scale. The subjects received 1minute of repetitive resistive-loaded breathing three times with 1minute interval. During these process, brain activity was analyzed by 3 Tesla scanner (Signa Excite HD; GE Healthcare).   Results:  Activation of bilateral sensory cortices was recorded among 6 normal subjects and 4 COPD patients. In addition, VPM in bilateral thalami was also activated in all subjects when subjects breathed with the resistive load. There was no difference of the localization of activated portions during resistive-loaded breathing between in normal subjects and in COPD patients. Values of the resistive load to induce thalamic and cortical activation were significantly lower in COPD patients than those in normal subjects.   Conclusion:  Activation of thalamus and sensory cortex was dependent on the resistive load among normal subjects and COPD patients. The resistive loads on COPD patients to induce the thalamic activation were significantly lower than those on the normal subjects.
Treatment of gastro-oesophageal reflux disease in adults
Authors: O Chassany, J F Bergmann, C Caulin, A. Haycox, S. Barton, T Walley, J. P. Galmiche, C. Scarpignato
Journal: BMJ (1999)

Suboptimal ward care of critically ill patients Suboptimal care should have been definedEditor-McQuillan et al show that most patients receive suboptimal management of oxygen therapy, airway, breathing, circulation, and monitoring before admission to intensive care. 1 In an area of medicine renowned for objective measurement it is surprising that this study should rely on the subjective opinions of two assessors about what constituted suboptimal care.Understandably, their opinions often disagreed.The authors accept that there are difficulties in relying on assessors' opinions, but we must not underestimate these limitations.The assessors knew the outcomes of the patients, which must have biased their opinions, particularly since suboptimal care is not defined.How suboptimal care was defined is crucial to the paper's message, and more information about the data evaluated by the assessors would have been preferable to the lengthy discussion, much of which was not directly related to the data.Unfortunately, many of the data are self fulfilling.It is unsurprising that the suboptimally managed group scored badly on oxygen therapy and airway, breathing, and circulation and that 67% of this group were late admissions to intensive care since these were presumably the factors used to determine suboptimal management.Nevertheless, a key message is that most of the well managed patients were admitted to intensive care units within the first day of admission, with presumably some going straight from accident and emergency.These acutely ill patients are perhaps more easily identifiable as going to need intensive care.Conversely, those patients who arrived at hospital less ill and who deteriorated while on general wards were those who received suboptimal care.There was a longer time between admission to hospital and admission to intensive care in these patients.We are not told if any of the admissions to intensive care were delayed because of lack of beds.Although there is no excuse for suboptimal care, sometimes admission to intensive care is requested because a ward with overstretched nursing staff and no high dependency beds recognises that it is unable to provide optimal care for an acutely ill patient.
LBA-06 INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib (REG) in refractory advanced oesophagogastric cancer (AOGC) - A study by the Australasian Gastrointestinal Trials Group (AGITG): Final overall and subgroup results
Authors: N. Pavlakis, K.M. Sjoquist, E. Tsobanis, A.J. Martin, Y-K. Kang, Y-J. Bang, C.J. O'Callaghan, N.C. Tebbutt, S.Y. Rha, J. Lee, J.Y. Cho, L.R. Lipton, M.J. Burnell, T. Alcindor, A. Strickland, J.W. Kim, S. Yip, J. Simes, J.R. Zalcberg, D. Goldstein
Journal: Annals of Oncology (2015)
Review of Late Complications of Treatment and Late Relapse in Testicular Cancer
Authors: Eleni Efstathiou, Christopher J. Logothetis
Journal: Journal of the National Comprehensive Cancer Network (2006)

With testicular cancer, a disease with a cure rate of 95%, the challenge is to restore quality of life to pretreatment levels and sustain it long-term. Although the implementation of guidelines and optimization of treatment modalities over the past years have served this purpose, some complications remain inevitable and experts are still challenged with late complications of outdated treatment standards. This article focuses on the late complications of cisplatin-based chemotherapy without disregarding those of currently applied infradiaphragmatic radiation. The most serious long-term complications of chemotherapy or radiotherapy are cardiovascular toxicity and second malignancies, as each has a 25-year risk of approximately 16%. Compared with the general population, risk for second malignancies remains significantly increased for at least 35 years after treatment. Chemotherapy-related cardiovascular toxicity is probably a result of both direct endothelial damage induced by cisplatin and indirect hormonal and metabolic changes. The increased incidence of the metabolic syndrome identified in long-term survivors is most likely associated with the lower testosterone levels reported. Cisplatin-based chemotherapy affects not only Leydig cells but also Sertoli and germ cells, resulting in infertility in 30% to 50% of testicular cancer patients treated with chemotherapy. Chronic neurotoxicity occurs in half of men, whereas permanent ototoxicity and some degree of renal function impairment occur in up to 30%. Pulmonary fibrosis, occurring in 5% to 10% of patients treated with bleomycin, is fatal in 1%. Although current treatment of advanced disease has changed its natural course, we are challenged by an increasing incidence of late relapse, an entity with a distinct tumor biology characterized by latency and chemoresistance.
The DNAJB1‐PRKACA chimera: Candidate biomarker and therapeutic target for fibrolamellar carcinomas
Authors: Lola M. Reid, Praveen Sethupathy
Journal: Hepatology (2015)

1Department of Cell Biology and PhysiologyUNC School of MedicineChapel HillNC 2Program in Molecular Biology and BiotechnologyUNC School of MedicineChapel HillNC 3Lineberger Comprehensive Cancer CenterUNC School of MedicineChapel HillNC 4Department of GeneticsUNC School of MedicineChapel HillNC
CD33 modulates TREM2: convergence of Alzheimer loci
Authors: Gail Chan, Charles C White, Phoebe A Winn, Maria Cimpean, Joseph M Replogle, Laura R Glick, Nicole E Cuerdon, Katie J Ryan, Keith A Johnson, Julie A Schneider, David A Bennett, Lori B Chibnik, Reisa A Sperling, Elizabeth M Bradshaw, Philip L De Jager
Journal: Nature Neuroscience (2015)
Fibrin Accumulation Secondary to Loss of Plasmin‐Mediated Fibrinolysis Drives Inflammatory Osteoporosis in Mice
Authors: Heather A. Cole, Tetsuro Ohba, Jeffry S. Nyman, Haro Hirotaka, Justin M. M. Cates, Matthew J. Flick, Jay L. Degen, Jonathan G. Schoenecker
Journal: Arthritis & Rheumatology (2014)

Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related comorbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αM β2 binding motif. Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αM β2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αM β2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels. Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology.
Breath by breath specific airway resistance during panting in children
Authors: Laurianne Coutier, Claude Bonabel, Bruno Demoulin, Iulia Ioan, Than Le Tuan, Silvia Varechova, Cyril Schweitzer, François Marchal
Journal: European Respiratory Journal (2012)

Rationale . Panting is the optimal way to minimize the phase lag between the plethysmographic volume compression signal (Vplet) and airflow due to the thermal artifact when measuring specific airway resistance (sRaw). A drawback in children is that the end expiratory lung volume may be observed to increase during the measurement. It is not known to what extent sRaw is altered by the breathing strategy.   The hypothesis  was tested here that increased end expiratory lung volume during panting does not impact significantly on sRaw.   Objective . To test whether increased end expiratory lung level within the sRaw acquisition results in a systematic trend with time.   Methods . sRaw was measured in 10 children panting in a custom made pressure plethysmograph. Thirty measurements (1-5 per subject) that displayed a steady increase in end expiratory lung level throughout at least 4 breaths were reanalyzed breath by breath.   Results.  Panting frequency (mean ± SD) was 3.1 ± 0.5 Hz. sRaw was found to increase significantly throughout the acquisition (p = 0.006).   Conclusion:  The progressive increase in end-expiratory lung volume during panting in children is associated with parallel increase in sRaw. This may be explained by non linearities in the Vplet - airflow relationship while the end expiratory lung volume increases in relation with imbalance between inspiratory and expiratory efforts. The clinical relevance is not clear and desserves further evaluation.
Acute Organic Brain Syndrome: A Complication of Disulfiram Therapy
Authors: STEVEN T. KNEE, JAVAD RAZANI
Journal: American Journal of Psychiatry (1974)

Consecutive admissions over a three-month period to a general psychiatric ward in a large urban medical center were reviewed for the presence of acute organic brain syndrome in patients being treated with disulfiram for chronic alcoholism. Five such cases were identified. The patients had initially been misdiagnosed as schizophrenic and had been treated with psychotropic medications, generally with less than optimum results. The authors suggest the withdrawal of the offending agent and the use of supportive measures and sedation rather than major psychotropic medication as the treatments of choice for this syndrome.
Chromosome Studies in the MB Mouse Lymphosarcoma<xref ref-type="fn" rid="fn1">2</xref>
Authors: W M DE BRUYN, E HANSEN-MELANDER
Journal: JNCI Journal of the National Cancer Institute (1962)

Of the MB mouse lymphosarcoma, which originated in 1935, several strains and substrains were grown in vivo or in vitro. Sixteen were analyzed chromosomally. There are four groups of strains, some of them with substrains: 1) Lymphoblasts grown strictly in vivo were designated Tu MB1a and 1b (s = 78 to 79 telocentrics). The polyploidization probably took place in 1953 at a critical period of growth. 2) The primary line in vitro of lymphoblasts (MB I) was composed of two kinds of cells, tumor-positive lymphoblasts (s = either 39 telocentrics plus 1 metacentric or 41 telocentrics) and, in addition, of tumor-negative fibroblasts (s = 53 telocentrics plus 3 metacentrics, as a substrain of MB II). MB VIa and MB E15 are substrains of lymphoblasts in vitro. Substrains of lymphoblasts in vivo were established in 1953 and designated Tu MB 1c and 1d (s = 39 telocentrics plus 1 metacentric). 3) Tumor-negative fibroblasts grown in vitro (s = 43 telocentrics plus 3 metacentrics, cell strain MB II). The substrains were the fibroblasts of strain MB I and the fibroblasts of strain MB IV. 4) Tumor-negative lymphoblasts, grown in vitro, cell strain MB III hypodiploid with up to a 50 percent incidence of metacentrics. The substrains were lymphoblasts MB III′ns; lymphoblasts MB III′p; lymphoblasts of strain MB IV; lymphoblasts MB V and MB V′. Tumor-positive lymphoblasts with 41 chromosome arms are remarkably stable chromosomally. The tumor-negative lymphoblasts probably lost one specific control mechanism that, among other things, caused hypodiploidy by permitting formation of metacentrics. The present study shows that within the MB substrains there is no relationship between gross changes of chromosome complement and malignancy. However, the tumor-producing lymphoblasts remain remarkably stable, always having 41 chromosome arms. These may appear either as 41 telocentrics or as 39 telocentrics plus 1 metacentric.
Cold weather kills far more people than hot weather, study shows
Authors: S. Mayor
Journal: BMJ (2015)

<h3>Abstract</h3> Acid sphingomyelinase (Asm) and acid ceramidase (Ac) are parts of the sphingolipid metabolism. Asm hydrolyzes sphingomyelin to ceramide, which is further metabolized to sphingosine by Ac. Ceramide generates ceramide-enriched platforms that are involved in receptor clustering within cellular membranes. However, the impact of cell-intrinsic ceramide on T cell function is not well characterized. By using T cell-specific Asm- or Ac-deficient mice, with reduced or elevated ceramide levels in T cells, we identified ceramide to play a crucial role in T cell function <i>in vitro</i> and <i>in vivo</i>. T cell-specific ablation of Asm in Asm<sup>flox/flox</sup>/CD4cre mice resulted in enhanced tumor progression associated with impaired T cell responses, whereas Ac<sup>flox/flox</sup>/CD4cre mice showed reduced tumor growth rates and elevated T cell activation compared to the respective controls upon tumor transplantation. Further <i>in vitro</i> analysis revealed that decreased ceramide content supports CD4<sup>+</sup> regulatory T cell differentiation and interferes with cytotoxic activity of CD8<sup>+</sup> T cells. In contrast, elevated ceramide concentration in CD8<sup>+</sup> T cells from Ac<sup>flox/flox</sup>/CD4cre mice was associated with enhanced cytotoxic activity. Strikingly, ceramide co-localized with the T cell receptor (TCR) and CD3 in the membrane of stimulated T cells and phosphorylation of TCR signaling molecules was elevated in Ac-deficient T cells. Hence, our results indicate that modulation of ceramide levels, by interfering with the Asm or Ac activity has an effect on T cell differentiation and function and might therefore represent a novel therapeutic strategy for the treatment of T cell-dependent diseases such as tumorigenesis.
Digital Microfluidic Cell Culture
Authors: Alphonsus H.C. Ng, Bingyu Betty Li, M. Dean Chamberlain, Aaron R. Wheeler
Journal: Annual Review of Biomedical Engineering (2015)

Digital microfluidics (DMF) is a droplet-based liquid-handling technology that has recently become popular for cell culture and analysis. In DMF, picoliter- to microliter-sized droplets are manipulated on a planar surface using electric fields, thus enabling software-reconfigurable operations on individual droplets, such as move, merge, split, and dispense from reservoirs. Using this technique, multistep cell-based processes can be carried out using simple and compact instrumentation, making DMF an attractive platform for eventual integration into routine biology workflows. In this review, we summarize the state-of-the-art in DMF cell culture, and describe design considerations, types of DMF cell culture, and cell-based applications of DMF.
rAAV-CFTRΔR Rescues the Cystic Fibrosis Phenotype in Human Intestinal Organoids and Cystic Fibrosis Mice
Authors: Dragana Vidović, Marianne S. Carlon, Mélanie F. da Cunha, Johanna F. Dekkers, Monika I. Hollenhorst, Marcel J. C. Bijvelds, Anabela S. Ramalho, Chris Van den Haute, Marc Ferrante, Veerle Baekelandt, Hettie M. Janssens, Kris De Boeck, Isabelle Sermet-Gaudelus, Hugo R. de Jonge, Rik Gijsbers, Jeffrey M. Beekman, Aleksander Edelman, Zeger Debyser
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Gene therapy holds promise for a curative mutation-independent treatment applicable to all patients with cystic fibrosis (CF). The various viral vector-based clinical trials conducted in the past have demonstrated safety and tolerance of different vectors, but none have led to a clear and persistent clinical benefit. Recent clinical breakthroughs in recombinant adeno-associated viral vector (rAAV)-based gene therapy encouraged us to reexplore an rAAV approach for CF.We evaluated the preclinical potential of rAAV gene therapy for CF to restore chloride and fluid secretion in two complementary models: intestinal organoids derived from subjects with CF and a CF mouse model, an important milestone toward the development of a clinical rAAV candidate for CF gene therapy.We engineered an rAAV vector containing a truncated CF transmembrane conductance regulator (CFTRΔR) combined with a short promoter (CMV173) to ensure optimal gene expression. A rescue in chloride and fluid secretion after rAAV-CFTRΔR treatment was assessed by forskolin-induced swelling in CF transmembrane conductance regulator (CFTR)-deficient organoids and by nasal potential differences in ΔF508 mice.rAAV-CFTRΔR transduction of human CFTR-deficient organoids resulted in forskolin-induced swelling, indicating a restoration of CFTR function. Nasal potential differences demonstrated a clear response to low chloride and forskolin perfusion in most rAAV-CFTRΔR-treated CF mice.Our study provides robust evidence that rAAV-mediated gene transfer of a truncated CFTR functionally rescues the CF phenotype across the nasal mucosa of CF mice and in patient-derived organoids. These results underscore the clinical potential of rAAV-CFTRΔR in offering a cure for all patients with CF in the future.