tbuckley/cabot-search huggingface dataset:
Cell volume regulation in oocytes and early embryos: connecting physiology to successful culture media
Authors: J. M. Baltz, A. P. Tartia
Journal: Human Reproduction Update (2009)

Preimplantation embryos are particularly susceptible to in vitro developmental blocks. These could be alleviated by lowering culture medium osmolarity. Because mammalian cells regulate their volumes by adjusting intracellular osmotic pressure, cell volume regulation could be critical to early embryos. We reviewed the literature on cell volume regulation in preimplantation embryos and the effects of increased osmolarity on embryo development, focusing also on the relation with improvements in embryo culture media. Embryos failed to develop from fertilized oocytes when osmolarity is increased. This could be alleviated by decreasing osmolarity or including certain compounds such as certain amino acids. Early preimplantation mouse embryos require intracellular accumulation of glycine to provide osmotic support and thus control cell volume. The glycine-specific transporter, GLYT1, mediates osmoregulated glycine accumulation in mouse embryos and likely in human embryos. GLYT1 is activated during meiotic maturation starting at ovulation. Prior to this, oocyte size is not independently controlled but instead is determined by strong adhesion between the oocyte plasma membrane and the inner surface of the zona pellucida. Early preimplantation embryos are particularly sensitive to increased osmolarity, and require the importation of glycine to regulate their cell volumes using a mechanism unique to early embryos. Cell volume regulation first appears when ovulation is triggered, oocyte zona pellucida adhesion is released, and glycine transport is activated. The requirement for supporting these physiological functions in oocytes and embryos should be taken into account when developing and improving systems for in vitro oocyte maturation and embryo culture.
Association of Somatic Mutations of<i>ADAMTS</i>Genes With Chemotherapy Sensitivity and Survival in High-Grade Serous Ovarian Carcinoma
Authors: Yuexin Liu, Maya Yasukawa, Kexin Chen, Limei Hu, Russell R. Broaddus, Li Ding, Elaine R. Mardis, Paul Spellman, Douglas A. Levine, Gordon B. Mills, Ilya Shmulevich, Anil K. Sood, Wei Zhang
Journal: JAMA Oncology (2015)

Chemotherapy response in the majority of patients with ovarian cancer remains unpredictable.To identify novel molecular markers for predicting chemotherapy response in patients with ovarian cancer.Observational study of genomics and clinical data of high-grade serous ovarian cancer cases with genomic and clinical data made public between 2009 and 2014 via the Cancer Genome Atlas project.Chemotherapy response (primary outcome) and overall survival (OS), progression-free survival (PFS), and platinum-free duration (secondary outcome).In 512 patients with ovarian cancer with available whole-exome sequencing data, mutations from 8 members of the ADAMTS family (ADAMTS mutations) with an overall mutation rate of approximately 10.4% were associated with a significantly higher chemotherapy sensitivity (100% for ADAMTS-mutated vs 64% for ADAMTS wild-type cases; P < .001) and longer platinum-free duration (median platinum-free duration, 21.7 months for ADAMTS-mutated vs 10.1 months for ADAMTS wild-type cases; P = .001). Moreover, ADAMTS mutations were associated with significantly better OS (hazard ratio [HR], 0.54 [95% CI, 0.42-0.89]; P = .01 and median OS, 58.0 months for ADAMTS-mutated vs 41.3 months for ADAMTS wild-type cases) and PFS (HR, 0.42 [95% CI, 0.38-0.70]; P < .001 and median PFS, 31.8 for ADAMTS-mutated vs 15.3 months for ADAMTS wild-type cases). After adjustment by BRCA1 or BRCA2 mutation, surgical stage, residual tumor, and patient age, ADAMTS mutations were significantly associated with better OS (HR, 0.53 [95% CI, 0.32-0.87]; P = .01), PFS (HR, 0.40 [95% CI, 0.25-0.62]; P < .001), and platinum-free survival (HR, 0.45 [95% CI, 0.28-0.73]; P = .001). ADAMTS-mutated cases exhibited a distinct mutation spectrum and were significantly associated with tumors with a higher genome-wide mutation rate than ADAMTS wild-type cases across the whole exome (median mutation number per sample, 121 for ADAMTS-mutated vs 69 for ADAMTS wild-type cases; P < .001).ADAMTS mutations may contribute to outcomes in ovarian cancer cases without BRCA1 or BRCA2 mutations and may have important clinical implications.
Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials
Authors: Christian T Ruff, Robert P Giugliano, Eugene Braunwald, Elaine B Hoffman, Naveen Deenadayalu, Michael D Ezekowitz, A John Camm, Jeffrey I Weitz, Basil S Lewis, Alexander Parkhomenko, Takeshi Yamashita, Elliott M Antman
Journal: The Lancet (2013)
Influence of Calcium-Sensing Receptor Gene on Urinary Calcium Excretion in Stone-Forming Patients
Authors: Giuseppe Vezzoli, Annalisa Tanini, Luigi Ferrucci, Laura Soldati, Cristiana Bianchin, Francesco Franceschelli, Cecilia Malentacchi, Berardino Porfirio, Donatella Adamo, Annalisa Terranegra, Alberto Falchetti, Daniele Cusi, Giuseppe Bianchi, Maria Luisa Brandi
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Calcium-sensing receptor (CaSR) is a plasma membrane protein that regulates tubular reabsorption of Ca. To establish its role in idiopathic hypercalciuria, the association of urinary Ca excretion with the polymorphisms of CASR gene has been studied in healthy subjects and in hypercalciuric and normocalciuric Ca stone formers. CASR exon 7 single nucleotide polymorphisms (SNP), G/T at codon 986, G/A at codon 990, and C/G at codon 1011, were evaluated by PCR amplification and direct sequencing in 97 normocalciuric stone formers, 134 hypercalciuric stone formers, and 101 normocalciuric healthy controls. Four haplotypes were defined on the basis of CASR gene SNP: haplotype 1 was characterized by the most frequent sequence; haplotypes 2, 3, or 4 by the presence of a single polymorphic variant at codon 986, 990, or 1011, respectively. The relative risk of hypercalciuria was calculated with multinomial logistic regression and was significantly increased only in individuals carrying haplotype 3 (Odds ratio, 13.0 [95% confidence interval, 1.7 to 99.4]). Accordingly, Ca excretion was higher in subjects bearing haplotype 3, whereas those bearing haplotype 2 showed a slight increase of plasma Ca concentration. Multiple regression analysis showed that haplotype 3 explained 4.1% of the total variance of Ca excretion and 12.6% of the variance explained by the variables considered in the study. In conclusion, CASR gene could be a component of the complex genetic background regulating Ca excretion. Arg990Gly polymorphism could facilitate activation of CaSR and increase Ca excretion and susceptibility to idiopathic hypercalciuria.
Unmeasured Costs of a Child's Death: Perceived Financial Burden, Work Disruptions, and Economic Coping Strategies Used by American and Australian Families Who Lost Children to Cancer
Authors: Veronica Dussel, Kira Bona, John A. Heath, Joanne M. Hilden, Jane C. Weeks, Joanne Wolfe
Journal: Journal of Clinical Oncology (2011)

Financial concerns represent a major stressor for families of children with cancer but remain poorly understood among those with terminally ill children. We describe the financial hardship, work disruptions, income loss, and coping strategies of families who lost children to cancer.Retrospective cross-sectional survey of 141 American and 89 Australian bereaved parents whose children died between 1990 and 1999 and 1996 to 2004, respectively, at three tertiary-care pediatric hospitals (two American, one Australian). Response rate: 63%.Thirty-four (24%) of 141 families from US centers and 34 (39%) of 88 families from the Australian center reported a great deal of financial hardship resulting from their children's illness. Work disruptions were substantial (84% in the United States, 88% in Australia). Australian families were more likely to report quitting a job (49% in Australia v 35% in the United States; P = .037). Sixty percent of families lost more than 10% of their annual income as a result of work disruptions. Australians were more likely to lose more than 40% of their income (34% in Australia v 19% in the United States; P = .035). Poor families experienced the greatest income loss. After accounting for income loss, 16% of American and 22% of Australian families dropped below the poverty line. Financial hardship was associated with poverty and income loss in all centers. Fundraising was the most common financial coping strategy (52% in the United States v 33% in Australia), followed by reduced spending.In these US and Australian centers, significant household-level financial effects of a child's death as a result of cancer were observed, especially for poor families. Interventions aimed at reducing the effects of income loss may ease financial distress.
Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study
Authors: Hendrik Rosewich, Holger Thiele, Andreas Ohlenbusch, Ulrike Maschke, Janine Altmüller, Peter Frommolt, Birgit Zirn, Friedrich Ebinger, Hartmut Siemes, Peter Nürnberg, Knut Brockmann, Jutta Gärtner
Journal: The Lancet Neurology (2012)
Community-Integrated Home-Based Depression Treatment in Older Adults
Authors: Paul Ciechanowski, Edward Wagner, Karen Schmaling, Sheryl Schwartz, Barbara Williams, Paula Diehr, Jayne Kulzer, Shelly Gray, Cheza Collier, James LoGerfo
Journal: JAMA (2004)

Older adults with social isolation, medical comorbidity, and physical impairment are more likely to be depressed but may be less able to seek appropriate care for depression compared with older adults without these characteristics.To determine the effectiveness of a home-based program of detecting and managing minor depression or dysthymia among older adults.Randomized controlled trial with recruitment through community senior service agencies in metropolitan Seattle, Wash, from January 2000 to May 2003.One hundred thirty-eight patients aged 60 years or older with minor depression (51.4%) or dysthymia (48.6%). Patients had a mean of 4.6 (SD, 2.1) chronic medical conditions; 42% of the sample belonged to a racial/ethnic minority, 72% lived alone, 58% had an annual income of less than 10 000 dollars, and 69% received a form of home assistance.Patients were randomly assigned to the Program to Encourage Active, Rewarding Lives for Seniors (PEARLS) intervention (n = 72) or usual care (n = 66). The PEARLS intervention consisted of problem-solving treatment, social and physical activation, and potential recommendations to patients' physicians regarding antidepressant medications.Assessments of depression and quality of life at 12 months compared with baseline.At 12 months, compared with the usual care group, patients receiving the PEARLS intervention were more likely to have at least a 50% reduction in depressive symptoms (43% vs 15%; odds ratio [OR], 5.21; 95% confidence interval [CI], 2.01-13.49), to achieve complete remission from depression (36% vs 12%; OR, 4.96; 95% CI, 1.79-13.72), and to have greater health-related quality-of-life improvements in functional well-being (P =.001) and emotional well-being (P =.048).The PEARLS program, a community-integrated, home-based treatment for depression, significantly reduced depressive symptoms and improved health status in chronically medically ill older adults with minor depression and dysthymia.
CD45: A Critical Regulator of Signaling Thresholds in Immune Cells
Authors: Michelle L. Hermiston, Zheng Xu, Arthur Weiss
Journal: Annual Review of Immunology (2003)

Regulation of tyrosine phosphorylation is a critical control point for integration of environmental signals into cellular responses. This regulation is mediated by the reciprocal actions of protein tyrosine kinases and phosphatases. CD45, the first and prototypic receptor-like protein tyrosine phosphatase, is expressed on all nucleated hematopoietic cells and plays a central role in this process. Studies of CD45 mutant cell lines, CD45-deficient mice, and CD45-deficient humans initially demonstrated the essential role of CD45 in antigen receptor signal transduction and lymphocyte development. It is now known that CD45 also modulates signals emanating from integrin and cytokine receptors. Recent work has focused on regulation of CD45 expression and alternative splicing, isoform-specific differences in signal transduction, and regulation of phosphatase activity. From these studies, a model is emerging in which CD45 affects cellular responses by controlling the relative threshold of sensitivity to external stimuli. Perturbation of this function may contribute to autoimmunity, immunodeficiency, and malignancy. Moreover, recent advances suggest that modulation of CD45 function can have therapeutic benefit in many disease states.
Cyclooxygenase-2–Dependent Prostacyclin Formation and Blood Pressure Homeostasis
Authors: Ying Yu, Jane Stubbe, Salam Ibrahim, Wen-liang Song, Emer M. Symth, Colin D. Funk, Garret A. FitzGerald
Journal: Circulation Research (2009)

Cyclooxygenase (COX)-derived prostanoids (PGs) are involved in blood pressure homeostasis. Both traditional nonsteroidal antiinflammatory drugs (NSAIDs) that inhibit COX-1 and COX-2 and NSAIDs designed to be selective for inhibition of COX-2 cause sodium retention and elevate blood pressure.To elucidate the role of COX-2 in blood pressure homeostasis using COX-1>COX-2 mice, in which the COX-1 expression is controlled by COX-2 regulatory elements.COX-1>COX-2 mice developed systolic hypertension relative to wild types (WTs) on a high-salt diet (HSD); this was attenuated by a PGI(2) receptor agonist. HSD increased expression of COX-2 in WT mice and of COX-1 in COX-1>COX-2 mice in the inner renal medulla. The HSD augmented in all strains urinary prostanoid metabolite excretion, with the exception of the major PGI(2) metabolite that was suppressed on regular chow and unaltered by the HSD in both mutants. Furthermore, inner renal medullary expression of the receptor for PGI(2), but not for other prostanoids, was depressed by HSD in WT and even more so in both mutant strains. Increasing osmolarity augmented expression of COX-2 in WT renal medullary interstitial cells and again the increase in formation of PGI(2) observed in WTs was suppressed in cells derived from both mutants. Intramedullary infusion of the PGI(2) receptor agonist increased urine volume and sodium excretion in mice.These studies suggest that dysregulated expression of the COX-2 dependent, PGI(2) biosynthesis/response pathway in the renal inner renal medulla undermines the homeostatic response to a HSD. Inhibition of this pathway may contribute directly to the hypertensive response to NSAIDs.
Time course and significance of changes in hepatic fructose-2,6-bisphosphate levels during refeeding of fasted rats.
Authors: M Kuwajima, C B Newgard, D W Foster, J D McGarry
Journal: Journal of Clinical Investigation (1984)

The time course of changes in hepatic fructose-2,6-bisphosphate (F-2,6-P2) and glycogen content was examined in fasted rats infused with glucose intragastrically or allowed to eat a chow diet ad lib. Initial values for the two parameters were approximately 0.4 nmol/g and 2 mg/g of tissue, respectively. Contrary to what might have been expected on the basis of reported studies with hepatocytes exposed to glucose (i.e., a rapid elevation of F-2,6-P2), the rise in F-2,6-P2 levels in vivo was a late event. It began only 4-5 h after glucose administration or refeeding, at which time glycogen content had reached approximately 35 mg/g of tissue. Thereafter, [F-2,6-P2] climbed rapidly, attaining fed values in the region of 10 nmol/g as glycogen stores became maximal (approximately 60 mg/g of tissue). Although the biochemical basis for these changes is still unclear, the delayed increase in [F-2,6-P2] is entirely consistent with the fact that much of the glycogen deposited in liver in the early postprandial phase is gluconeogenic in origin. The later rise in [F-2,6-P2] likely represents a key signal for the attenuation of gluconeogenic carbon flow into glycogen as the latter approaches repletion levels.
Endocrine cells in diffuse pulmonary fibrosis.
Authors: N J Wilson, J R Gosney, F Mayall
Journal: Thorax (1993)

There is evidence to suggest, particularly from studies in animals, that the products of pulmonary endocrine cells, especially gastrin releasing peptide, may have a role in the pathogenesis of fibrosis in the lung. This study was carried out to examine the morphology, number, distribution, and content of pulmonary endocrine cells in tissue from 49 patients with diffuse pulmonary fibrosis.Twenty patients with interstitial pneumonitis, 17 with early fibrosis, and 12 with frank honeycombing were studied, together with five age matched controls without pulmonary disease. Endocrine cells were immunolabeled by the avidin-biotin complex method for two general markers (protein gene product 9.5 and neuron specific enolase) and a range of normal and aberrant secretory products.In the early stages, characterised by vigorous pneumonitis, endocrine cells were normal in appearance and distribution but very few in number. They contained only those secretory products normally found in such cells in health; inappropriate substances were not seen. By the time of early fibrosis endocrine cells were even fewer. None were identifiable in the lungs affected by honeycombing, despite the fact that all contained intact, well preserved epithelium.It seems unlikely that the products of pulmonary endocrine cells can have any role in the pathogenesis of diffuse pulmonary fibrosis in man, the diminution in their number with advancing fibrosis probably reflecting their loss simply as a consequence of generalised epithelial damage.
A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine
Authors: S.D. Undevia, H.L. Kindler, L. Janisch, S.C. Olson, R.L. Schilsky, N.J. Vogelzang, K.A. Kimmel, T.A. Macek, M.J. Ratain
Journal: Annals of Oncology (2004)
Systematic review of studies of patient satisfaction with telemedicine
Authors: F. Mair
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To review research into patient satisfaction with teleconsultation, specifically clinical consultations between healthcare providers and patients involving real time interactive video. <b>Design:</b> Systematic review of telemedicine satisfaction studies. Electronic databases searched include Medline, Embase, Science Citation Index, Social Sciences Citation Index, Arts and Humanities Citation Index, and the TIE (Telemedicine Information Exchange) database. <b>Subjects:</b> Studies conducted worldwide and published between 1966 and 1998. <b>Main outcome measures:</b> Quality of evidence about patient satisfaction. <b>Results:</b> 32 studies were identified. Study methods used were simple survey instruments (26 studies), exact methods not specified (5), and qualitative methods (1). Study designs were randomised controlled trial (1 trial); random patient selection (2); case-control (1); and selection criteria not specified or participants represented consecutive referrals, convenience samples, or volunteers (28). Sample sizes were20 (10 trials),100 (14), &gt;100 (7), and not specified (1). All studies reported good levels of patient satisfaction. Qualitative analysis revealed methodological problems with all the published work. Even so, important issues were highlighted that merit further investigation. There is a paucity of data examining patients9 perceptions or the effects of this mode of healthcare delivery on the interaction between providers and clients. <b>Conclusions:</b> Methodological deficiencies (low sample sizes, context, and study designs) of the published research limit the generalisability of the findings. The studies suggest that teleconsultation is acceptable to patients in a variety of circumstances, but issues relating to patient satisfaction require further exploration from the perspective of both clients and providers.
Dendritic Cells in Cancer Immunotherapy
Authors: Lawrence Fong, Edgar G. Engleman
Journal: Annual Review of Immunology (2000)

The potential to harness the potency and specificity of the immune system underlies the growing interest in cancer immunotherapy. One such approach uses bone marrow–derived dendritic cells, phenotypically distinct and extremely potent antigen-presenting cells, to present tumor-associated antigens and thereby generate tumor-specific immunity. Support for this strategy comes from animal studies that have demonstrated that dendritic cells, when loaded ex vivo with tumor antigens and administered to tumor-bearing hosts, can elicit T cell–mediated tumor destruction. These observations have led to clinical trials designed to investigate the immunologic and clinical effects of antigen-loaded dendritic cells administered as a therapeutic vaccine to patients with cancer. In the design and conduct of such trials, important considerations include antigen selection, methods for introducing the antigen into MHC class I and II processing pathways, methods for isolating and activating dendritic cells, and route of administration. Although current dendritic cell–based vaccination methods are cumbersome, promising results from clinical trials in patients with malignant lymphoma, melanoma, and prostate cancer suggest that immunotherapeutic strategies that take advantage of the antigen presenting properties of dendritic cells may ultimately prove both efficacious and widely applicable to human tumors.
FAILURE TO TRANSFER TUBERCULIN SENSITIVITY PASSIVELY WITH PLASMA FRACTIONS CONTAINING ALPHA GLOBULIN
Authors: N. Joel Ehrenkranz, Byron H. Waksman
Journal: The Journal of Experimental Medicine (1956)

We are unable to confirm the observations reported by Cole and Favour that passive transfer of plasma fractions containing alpha globulin (IV + V or IV-10) from tuberculin-sensitive guinea pigs confers delayed sensitivity to tuberculoprotein upon normal animals. In guinea pigs with chronic cervical adenitis due to infection with group C hemolytic streptococci, injection of fraction IV + V and repeated skin tests with PPD induced indurated skin reactions of 9 to 10 mm., maximal at 24 hours, and, in one experiment, a positive tissue culture response to tuberculin. It is suggested that this reactivity was actively induced. Normal or infected recipients of fraction I + II + III from the plasma of tuberculin-sensitive donors manifested edematous responses to tuberculopolysaccharide, maximal at 4 to 6 hours, as reported. Skin tests with pneumococcal C polysaccharide revealed no evidence of passive transfer of C-reactive protein in fractions I + II + III or IV + V.
Comment on: Rowan et al. Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU): Body Composition at 2 Years of Age. Diabetes Care 2011;34:2279–2284
Authors: Linda A. Barbour, Rachael E. Van Pelt, David E. Brumbaugh, Teri L. Hernandez, Jacob E. Friedman
Journal: Diabetes Care (2012)

We applaud Dr. Rowan and the MiG TOFU (Metformin in Gestational diabetes: The Offspring Follow-Up) investigators for their intense efforts at following the 2-year offspring outcomes from the MiG trial (1). Understanding how in utero exposures impact longer-term offspring consequences is critical. However, we feel compelled to caution against overinterpretation of this study's findings.

Of note, 46% of the mothers in the metformin group required insulin to achieve adequate glycemic control (1); therefore, ∼50% in this group actually received both. Although 43% of the total infant cohort received anthropometric measures at 2 years, only ∼15% received dual-energy X-ray absorptiometry (DEXA) scans, thus potentially biasing the results. The absence of any differences in the …