tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Treatments for Adolescent Depression: Results From TADS
Authors: Marisa Elena Domino, Barbara J. Burns, Susan G. Silva, Christopher J. Kratochvil, Benedetto Vitiello, Mark A. Reinecke, Jeremy Mario, John S. March
Journal: American Journal of Psychiatry (2008)

While the evidence base for treatments for adolescent depression is building, little is known about the relative efficiency of such treatments. Treatment costs are a relevant concern given the competing demands on family and health care budgets. The authors evaluated the cost-effectiveness of three active treatments among adolescents with major depressive disorder.Volunteers (N=439) ages 12 to 18 with a primary diagnosis of major depressive disorder participated in a randomized, controlled trial conducted at 13 U.S. academic and community clinics from 2000 to 2004. Subjects included those participants who did not drop out and had evaluable outcome and cost data at 12 weeks (N=369). Subjects were randomly assigned to 12 weeks of either fluoxetine alone (10-40 mg/day), CBT alone, CBT combined with fluoxetine (10-40 mg/day), or placebo (equivalent to 10-40 mg/day). Both placebo and fluoxetine were administered double-blind; CBT alone and CBT in combination with fluoxetine were administered unblinded. Societal cost per unit of improvement on the Children's Depression Rating Scale-Revised and cost per quality-adjusted life year (QALY) were compared.Results ranged from an incremental cost over placebo of $24,000 per QALY for treatment with fluoxetine to $123,000 per QALY for combination therapy treatment. The cost-effectiveness ratio for CBT treatment was not evaluable due to negative clinical effects. The models were robust on a variety of assumptions.Both fluoxetine and combination therapy are at least as cost-effective in the short-term as other treatments commonly used in primary care (using a threshold of $125,000/QALY). Fluoxetine is more cost-effective than combination therapy after 12 weeks of treatment.
Functional Morphometric Analysis in Cellular Behaviors: Shape and Size Matter
Authors: Haiyang Yu, Kee Pah Lim, Sijing Xiong, Lay Poh Tan, Winston Shim
Journal: Advanced Healthcare Materials (2013)

Abstract Cellular morphogenesis in response to biophysical and topographical cues provides insights into cytoskeletal status, biointerface communications, and phenotypic adaptations in an incessant signaling feedback that governs cellular fate. Morphometric characterization is an important element in the study of the dynamic cellular behaviors, in their interactive response to environmental influence exerted by culture system. They collectively serve to reflect cellular proliferation, migration, and differentiation, which may serve as prognostic indices for clinical and pathological diagnosis. Various parameters are proposed to categorize morphological adaptations in relation to cellular function. In this review, the underlying principles, assumptions, and limitations of morphological characterizations are discussed. The significance, challenges, and implications of quantitative morphometric characterization of cell shapes and sizes in determining cellular functions are discussed.
Phase II Trial of Palliative Radiotherapy for Hepatocellular Carcinoma and Liver Metastases
Authors: Hany Soliman, Jolie Ringash, Haiyan Jiang, Kawalpreet Singh, John Kim, Robert Dinniwell, Anthony Brade, Rebecca Wong, James Brierley, Bernard Cummings, Camilla Zimmermann, Laura A. Dawson
Journal: Journal of Clinical Oncology (2013)

To evaluate the feasibility and response of liver radiotherapy (RT) in improving symptoms and quality of life in patients with hepatocellular carcinoma (HCC) or liver metastases (LM).Eligible patients had HCC or LM, unsuitable for or refractory to standard therapies, with an index symptom of pain, abdominal discomfort, nausea, or fatigue. The Brief Pain Inventory (BPI), Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep), and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) were completed by patients at baseline and each follow-up. The primary outcome was the percentage of patients with a clinically significant change at 1 month in the BPI subscale of symptom on average in the past 24 hours. Secondary outcomes were improvement in other BPI subscales and at other time points, FACT-Hep and EORTC QLQ-C30 at each follow-up, and toxicity at 1 week.Forty-one patients (30 men and 11 women) with HCC (n = 21) or LM (n = 20) were accrued. At 1 month, 48% had an improvement in symptom on average in the past 24 hours. Fifty-two percent of patients had improvement in symptom at its worst, 37% at its least, and 33% now. Improvements in the FACT-G and hepatobiliary subscale were seen in 23% and 29% of patients, respectively, at 1 month. There were also improvements in EORTC QLQ-C30 functional (range, 11% to 21%) and symptom (range, 11% to 50%) domains. One patient developed grade 3 nausea at 1 week.Improvements in symptoms were observed at 1 month in a substantial proportion of patients. A phase III study of palliative liver RT is planned. [Corrected]
A detached island residents' smoking habits and their prevalence of COPD
Authors: Yorihide Yanagita, Kahori Oue, Takako Tanaka, Hideaki Senjyu
Journal: European Respiratory Journal (2012)

[BACKGROUND]

The prevalence of COPD is high worldwide. It has been reported that the prevalence rate of subjects aged 40 years and over is about 8.6% in Japan. However, no reports have examined the prevalence of COPD by region, such as whether there are differences in subjects living in urban areas, or on a detached island.

[AIMS AND OBJECTIVES]

The purpose of this study was to evaluate the influence of the region (mainland versus a detached island)on the general population's smoking habits and the prevalence of COPD or respiratory function. A general population of 5221 subjects was targeted.

[METHODS]

All of the candidates' health survey items (age, sex, body composition, smoking habit, Brinkman Index, respiratory function and COPD disease) were investigated. Candidates were classified into a mainland group and a detached island group according to the location of the institution that performed their medical checkup, and each health survey item and respiratory function parameter were compared.

For the statistical analysis, two-sample t-tests, chi-square tests, and Mann-Whitney U tests were used.

[RESULTS]

The former smoker' rate (mainland 51.7% vs detached island 73.7%,p<0.001) and Brinkman Index (mainland 322.0±494.7 vs detached island 406.2±446.7,p<0.001) were higher in the detached island group. Nevertheless, the prevalence of COPD was lower in the detached island group (mainland 8.5% vs detached island 7.0%,p<0.05).

[CONCLUSIONS]

According to the guidelines of the GOLD, tobacco smoke is a primary factor related to the development of COPD. Our findongs indicate that the living environment is also related to the prevalence of COPD.
Phase III Trial of High-Dose Sequential Chemotherapy With Peripheral Blood Stem Cell Support Compared With Standard Dose Chemotherapy for First-Line Treatment of Advanced Ovarian Cancer: Intergroup Trial of the AGO-Ovar/AIO and EBMT
Authors: Volker Möbus, Hannes Wandt, Norbert Frickhofen, Carmelo Bengala, Kim Champion, Rainer Kimmig, Helmut Ostermann, Axel Hinke, Jonathan A. Ledermann
Journal: Journal of Clinical Oncology (2007)

Although ovarian cancer is one of the most chemotherapy-sensitive solid tumors, cure after radical surgery and chemotherapy is uncommon. A randomized trial comparing high-dose sequential chemotherapy with peripheral blood stem cell (PBSC) support with platinum-based combination chemotherapy was conducted to investigate whether dose-intensification improves outcome.One hundred forty-nine patients with untreated ovarian cancer were randomly assigned after debulking surgery to receive standard combination chemotherapy or sequential high-dose (HD) treatment with two cycles of cyclophosphamide and paclitaxel followed by three cycles of HD carboplatin and paclitaxel with PBSC support. HD melphalan was added to the final cycle. The median age was 50 years (range, 20 to 65 years) and International Federation of Gynecology and Obstetrics stage was IIb/IIc in 4%, III in 78%, and IV in 17%.Seventy-six percent of patients received all five cycles in the HD arm and the main toxicities were neuro-/ototoxicity, gastrointestinal toxicity, and infection and one death from hemorrhagic shock. After a median follow-up of 38 months, the progression-free survival was 20.5 months in the standard arm and 29.6 months in the HD arm (hazard ratio [HR], 0.84; 95% CI, 0.56 to 1.26; P, .40). Median overall survival (OS) was 62.8 months in the standard arm and 54.4 months in the HD arm (HR, 1.17; 95% CI, 0.71 to 1.94; P, .54).This is the first randomized trial comparing sequential HD versus standard dose chemotherapy in first-line treatment of patients with advanced ovarian cancer. We observed no statistically significant difference in progression-free survival or OS and conclude that HD chemotherapy does not appear to be superior to conventional dose chemotherapy.
Prognostic Index for Acute- and Lymphoma-Type Adult T-Cell Leukemia/Lymphoma
Authors: Hiroo Katsuya, Takeharu Yamanaka, Kenji Ishitsuka, Atae Utsunomiya, Hidenori Sasaki, Shuichi Hanada, Tetsuya Eto, Yukiyoshi Moriuchi, Yoshio Saburi, Masaharu Miyahara, Eisaburo Sueoka, Naokuni Uike, Shinichiro Yoshida, Kiyoshi Yamashita, Kunihiro Tsukasaki, Hitoshi Suzushima, Yuju Ohno, Hitoshi Matsuoka, Tatsuro Jo, Junji Suzumiya, Kazuo Tamura
Journal: Journal of Clinical Oncology (2012)

Purpose The prognosis of acute- and lymphoma-type adult T-cell leukemia/lymphoma (ATL) is poor, but there is marked diversity in survival outcomes. The aim of this study was to develop a prognostic index (PI) for acute- and lymphoma-type ATL (ATL-PI). Patients and Methods In a retrospective review, data from 807 patients newly diagnosed with acute- and lymphoma-type ATL between January 2000 and May 2009 were evaluated. We randomly divided subjects into training (n = 404) and validation (n = 403) samples, and developed a PI using a multivariable fractional polynomial model. Results Median overall survival time (MST) for the 807 patients was 7.7 months. The Ann Arbor stage (I and II v III and IV), performance status (0 to 1 v 2 to 4), and three continuous variables (age, serum albumin, and soluble interleukin-2 receptor [sIL-2R]) were identified as independent prognostic factors in the training sample. Using these variables, a prognostic model was devised to identify different levels of risk. In the validation sample, MSTs were 3.6, 7.3, and 16.2 months for patients at high, intermediate, and low risk, respectively (P &lt; .001; χ 2 = 89.7, 2 df; log-rank test). We also simplified the original ATL-PI according to dichotomizing age at 70 years, serum albumin at 3.5 g/dL, and sIL-2R at 20,000 U/mL and developed an easily calculable PI with prognostic discrimination power (P &lt; .001; χ 2 = 74.2, 2 df; log-rank test). Conclusion The ATL-PI is a promising new tool for identifying patients with acute- and lymphoma-type ATL at different risks.
Diabetes In A Nonpancreatectomized Child With Nesidioblastosis
Authors: Bassam S. Bin-Abbas, Abdullah A. Al-Ashwal
Journal: Diabetes Care (2004)

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) (Online Mendelian Inheritance in Man [OMIM] 256450), formerly known as nesidioblastosis, is a glucose metabolism disorder characterized by profound hypoglycemia and inappropriate secretion of insulin (1). Affected children run the risk of severe neurological damage unless immediate and adequate steps are taken (2). Treatment with diazoxide and/or somatostatin analogue is the first line of therapy. However, it not always effective, especially in familial cases, which may necessitate an alternative intervention such as pancreatectomy (3).

Several studies have suggested that partial pancreatectomy endangers future islet cell function (4,5). The incidence of diabetes increases with age and correlates with the extent of surgical resection (6,7). However, there was no report of occurrence of overt diabetes in medically treated patients (8). In this report, we described an adolescent female with neonatal nesidioblastosis who developed diabetes after medical treatment with diazoxide/octreotide. To our knowledge, this is the first nesidioblasosis case subject who developed diabetes following medical therapy.

A 14-year-old Saudi female presented with severe persistent hypoglycemia during the first few …
Introductory remarks: environmental and endogenous hazards to the female reproductive system.
Authors: R L Butcher, R D Page
Journal: Environmental Health Perspectives (1981)

The toxic action of environmental chemicals on reproduction and the toxiclike effects of ovarian hormones have been shown by numerous investigators. Some toxic effects of environmental chemicals on reproduction are through their action on hormonal secretion. Such effects on the endocrine system could provide additional approaches to investigations of toxicity of compounds. A better understanding of interactions of environmental chemicals with the endocrine system is needed. Therefore, it becomes important for a greater exchange of information and more interaction between toxicologists and endocrinologists.
Safety, Pharmacokinetics, and Activity of ABX-EGF, a Fully Human Anti–Epidermal Growth Factor Receptor Monoclonal Antibody in Patients With Metastatic Renal Cell Cancer
Authors: Eric K. Rowinsky, Garry H. Schwartz, Jared A. Gollob, John A. Thompson, Nicholas J. Vogelzang, Robert Figlin, Ronald Bukowski, Naomi Haas, Pamela Lockbaum, Yu-Ping Li, Rosalin Arends, Kenneth A. Foon, Gisela Schwab, Janice Dutcher
Journal: Journal of Clinical Oncology (2004)

To determine the antitumor activity of ABX-EGF, a fully human monoclonal antibody to the epidermal growth factor receptor (EGFr), in previously treated patients with metastatic renal cell carcinoma, and to characterize its toxicity, immunogenicity, pharmacokinetics, and pharmacodynamics.The antitumor activity, as well as the toxicity, pharmacokinetics, pharmacodynamics, and immunogenicity of ABX-EGF, were assessed.Eighty-eight patients were treated with ABX-EGF doses of 1.0, 1.5, 2.0, or 2.5 mg/kg weekly with no loading dose. EGFr immunostaining was performed on 76 tumor biopsy specimens (86%), and 69 (91%) scored positive. Major responses occurred in three patients, and two patients had minor responses. Forty-four patients (50%) also had stable disease at their first 8-week assessment, and the median progression-free survival (PFS) was 100 days (95% CI, 58 to 140 days). Low hemoglobin and high alkaline phosphatase predicted for short PFS. The principal toxicity, an acneiform rash, occurred in 68%, 95%, 87%, and 100% of patients who received at least three doses of ABX-EGF at 1.0, 1.5, 2.0, and 2.5 mg/kg/wk, respectively. A trend indicated that the severity of the rash may relate to PFS. No human antihuman antibodies were detected. ABX-EGF pharmacokinetics fit a model that incorporated both linear and saturable EGFr-mediated clearance mechanisms, and interindividual variability was low. At 2.5 mg/kg/wk, ABX-EGF concentrations throughout treatment exceeded those estimated to saturate nonlinear clearance and inhibit xenograft growth by 90%.ABX-EGF was generally well tolerated. The objective response rate was low in previously treated patients with metastatic renal cell carcinoma. Although skin rash may be a pharmacodynamic marker of drug action, its potential as a surrogate marker of clinical benefit requires further evaluation.
A Discussion on Corporeal Endometritis: Its Frequency, Diagnosis, and Treatment
Authors: G. E. Herman
Journal: BMJ (1890)

ENDOMETRITIS of the body of the uterus seems to me a subject very fit for discussion at a representative mteeting such as this, because it is a disease about which we know comparatively little, and, therefore, one which needs discussion, and concerning which the student and practitioner find apparently conflicting stete- ments in the works to which they are accustomed to refer.Some authors speak of it as common, others think it so rare that they omit ib aplLogether.The explanation of this apparent conflict of opinion is this: that some authors refuse to admit the existence of endometritsis of the body of the uterus unless the diagnosis is more than an inforp""o is supported by some sort of demonstra- tion that inflammation is present, and that the lining membrane of the body of the uterus is its seat.Others, looking at the fact that in many minor maladies, (and not in those of the uterus only,) no demonstration of their existence or nature is ever attainable, and that in cases of corporeal endometritis which end in recovery the nature of the morbid changes never can be demonstrated by any means at present known to us, are satisfied with a diagnosis based only on inference from the signs and symptoms.In practice we must often act on a diagnosis based only on inference.Still a diagnosis based only on inference does not compel assent, but 'rather invites scepticism.What anatomical evidence ought we to require as proof of endo- metritis?We may accept the fact of its existence if we find products of inflammation-in a word pus-discharged from the body of the uterus.But the secretion of the body of the uterus comes to us through the cervical canal, and mixed with the secre- tions from that mucous membrane; and although attempts have been made to get the secretion of the body of the uterus separately from that of the cervix, there is no way in which that can be done without an amount of discomfort and risk to the patient quite incommensurate with any practical good that can at present result from doing so.And pus in the cavity of the body of the uterus is not of necessity therein produced.Pus in the tubes may escape into the uterus.Still, if we find a purulent discharge seen to come from the uterus, nQt merely clinging about the os uteri, or filling the cervical canal, but, after the cervix has been cleaned, distinctly flowing down into the lower and visible part of the cervical canal from the part of the canal which we cannot see; and we find no evidence of disease either of the cervix or of
Endogenous Control of Cell Cycle Progression by Autocrine Transforming Growth Factor β in Breast Cancer Cells
Authors: Sudhakar Ammanamanchi, Manoranjani P. M. Tillekeratne, Tien C. Ko, Michael G. Brattain
Journal: Cancer Research (2004)

Tumor progression due to loss of autocrine negative transforming growth factor-beta (TGF-beta) activity was reported in various cancers of epithelial origin. Estrogen receptor expressing (ER(+)) breast cancer cells are refractory to TGF-beta effects and exhibit malignant behavior due to loss or inadequate expression of TGF-beta receptor type II (RII). The exogenous TGF-beta effects on the modulation of cell cycle machinery were analyzed previously. However, very little is known regarding the endogenous control of cell cycle progression by autocrine TGF-beta. In this study, we have used a tetracycline regulatable RII cDNA expression vector to demonstrate that RII replacement reconstitutes autocrine negative TGF-beta activity in ER(+) breast cancer cells as evidenced by the delayed entry into S phase by the RII transfectants. Reversal of the delayed entry into S phase by the RII transfectants in the presence of tetracycline in addition to the decreased steady state transcription from a promoter containing the TGF-beta responsive element (p3TP-Lux) by TGF-beta neutralizing antibody treatment of the RII transfected cells confirmed that autocrine-negative TGF-beta activity was induced in the transfectants. Histone H1 kinase assays indicated that the delayed entry of RII transfectants into phase was associated with markedly reduced cyclin-dependent kinase (CDK)2 kinase activity. This reduction in kinase activity was due to the induction of CDK inhibitors p21/waf1/cip1 and p27/kip, and their association with CDK2. Tetracycline treatment of RII transfectants led to the suppression of p21/waf1/cip1and p27/kip expression, thus, directly demonstrating induction of CDK inhibitors by autocrine TGF-beta leading to growth control of ER(+) breast cancer cells.
Nucleotide Sequence Diversity at the Methionine Synthase Locus in Endangered Dunnia sinensis (Rubiaceae): An Evaluation of the Positive Selection Hypothesis
Authors: Yu-Chung Chiang, Xue-Jun Ge, Chang-Hung Chou, Wen-Lung Wu, Tzen-Yuh Chiang
Journal: Molecular Biology and Evolution (2002)

Methionine synthase is a key enzyme for the synthesis of the aspartate-derived methionine, the immediate precursor of S-adenosyl-methionine, which has been illustrated to be associated with plant growth and pathogen interactions. In this study we tested the positive selection hypothesis of molecular evolution of the methionine synthase gene in Dunnia sinensis. In the entire sample of 87 sequences, 22 haplotypes of introns and 16 haplotypes of exons were identified. An excess of polymorphism over the neutral expectation for the class of unique nucleotide polymorphisms was observed in both exon and intron sequences. Ten replacement substitutions versus six synonymous substitutions among lineages, although nonsignificant, revealed that some advantageous mutants might have been favored. The distribution of d(N)/d(S) > 1 at nodes between closely related haplotypes in the gene network also indicated weak and variable positive selection. Nevertheless, low levels of genetic diversity in exons (theta; = 0.0052) and introns (theta; = 0.0070) of the methionine synthase gene of the outcrossing Dunnia were also attributed to the endangered status of the species. The atpB-rbcL intergenic spacer of cpDNA and the ribosomal internal transcribed spacer of mtDNA were used to discern the relative effectiveness of natural selection from intrinsic evolutionary forces. The low levels of nucleotide polymorphisms in both organelle spacers and the significant population differentiation reflected the effect of population-species history and demography. Two major lineages of the methionine synthase gene genealogy were recovered corresponding to two geographic regions, a result that was consistent with organelle phylogenies. Both past fragmentation and recent habitat disturbance causing complete bottlenecks may have resulted in population decline and geographic isolation and may have led to the depletion of genetic variation at loci in nuclear and organelle genomes.