tbuckley/cabot-search huggingface dataset:
VHICA, a New Method to Discriminate between Vertical and Horizontal Transposon Transfer: Application to the<i>Mariner</i>Family within<i>Drosophila</i>
Authors: Gabriel Luz Wallau, Pierre Capy, Elgion Loreto, Arnaud Le Rouzic, Aurélie Hua-Van
Journal: Molecular Biology and Evolution (2015)

Transposable elements (TEs) are genomic repeated sequences that display complex evolutionary patterns. They are usually inherited vertically, but can occasionally be transmitted between sexually independent species, through so-called horizontal transposon transfers (HTTs). Recurrent HTTs are supposed to be essential in life cycle of TEs, which are otherwise destined for eventual decay. HTTs also impact the host genome evolution. However, the extent of HTTs in eukaryotes is largely unknown, due to the lack of efficient, statistically supported methods that can be applied to multiple species sequence data sets. Here, we developed a new automated method available as a R package "vhica" that discriminates whether a given TE family was vertically or horizontally transferred, and potentially infers donor and receptor species. The method is well suited for TE sequences extracted from complete genomes, and applicable to multiple TEs and species at the same time. We first validated our method using Drosophila TE families with well-known evolutionary histories, displaying both HTTs and vertical transmission. We then tested 26 different lineages of mariner elements recently characterized in 20 Drosophila genomes, and found HTTs in 24 of them. Furthermore, several independent HTT events could often be detected within the same mariner lineage. The VHICA (Vertical and Horizontal Inheritance Consistence Analysis) method thus appears as a valuable tool to analyze the evolutionary history of TEs across a large range of species.
Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study.
Authors: V Lorusso, A Catino, B Leone, M Rabinovich, G Gargano, A Paradiso, M De Lena
Journal: Journal of Clinical Oncology (1993)

This study aimed to evaluate the activity and toxicity of carboplatin (PPL) and ifosfamide (IFO) in patients with epithelial ovarian cancer previously treated with cisplatin (CDDP)-containing regimens.From July 1989 to December 1991, 35 patients with epithelial ovarian cancer relapsed or refractory to CDDP as first-line chemotherapy were treated. PPL was administered at a dose of 300 mg/m2 intravenously (IV) on day 1 and IFO at a dose of 1,500 mg/m2 IV on days 1 to 3 every 3 to 4 weeks. Criteria for evaluating previous response to CDDP were strictly defined.The overall response rate was 43% (complete response [CR], 6%; partial response [PR], 37%) and the median duration of response was 7 months (range, 3 to 16). In potentially platinum-sensitive (PPS; relapsed) patients, the overall response rate was 56%. None of the primary platinum-resistant (PPR) patients obtained a clinical response to PPL plus IFO, whereas one of five secondary platinum-resistant (SPR) patients obtained a PR. The regimen was easily manageable.PPL plus IFO is useful and well-tolerated combination in salvage treatment of patients with advanced ovarian cancer. However, clear synergism between PPL and IFO that could overcome intrinsic or acquired CDDP resistance was not observed. The advantage of PPL plus IFO as compared with CDDP-containing regimens is represented by the increased tolerability and the reduced neurotoxicity, nephrotoxicity, and ototoxicity as compared with CDDP-containing regimens. It is essential that the patient population be defined according to their previous response to platinum therapy in trials involving second-line therapy of ovarian cancer.
Incidence of adenoviral infections in children
Authors: Trajanka Ilievska, Gorica Popova
Journal: European Respiratory Journal (2012)

Adenoviruses are highly prevalent in children.  It is estimated that 3% of all infections, and approximately 7% of febrile conditions are caused by adenoviruses. During winter season they cause over 70% of all respiratory diseases.  Aim: To evaluate presence of antibodies on Adenoviruses in children sera, during 2011.  Material and methods: The sera from hospitalized children with symptoms of prolonged febrile conditions and cough were examined. Examination was performed by Indirect Immunofluorescent Assay –Pneumoslide IgM.  Results: During 2011, 217 sera samples were examined. Antibodies on Adenoviruses were confirmed in 59 (27.1%).  The investigations were made in all months, but in November, December, March, and surprisingly in July, detections were most frequently.  Conclusion: Adenoviral infections occur during whole year, they are common infections in children, and often result in and unnecessary hospitalization and antibiotic therapy. Identifying adenoviruses as the cause of illness can have significant influence on treatment and care, and in some instances may be life-saving.
Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues
Authors: Joseph J C Thome, Kara L Bickham, Yoshiaki Ohmura, Masaru Kubota, Nobuhide Matsuoka, Claire Gordon, Tomer Granot, Adam Griesemer, Harvey Lerner, Tomoaki Kato, Donna L Farber
Journal: Nature Medicine (2015)
A phase I study of thalidomide, capecitabine and temozolomide (TCT) in advanced cancer
Authors: M. I. Khan, C. Salvador, C. L. Schonard, B. S. Taft, G. H. Kloecker, D. A. Laber
Journal: Journal of Clinical Oncology (2006)

13122 Background: The aim is to develop a novel oral immuno-chemotherapy regimen against advanced cancers. Methods: Patients were enrolled in cohorts of 3 or 6 in a standard phase I design. Thalidomide 100 mg was kept stable for all cohorts. If well tolerated after 1 week, capecitabine and temozolomide (TCT) were given daily without rest and escalated one at a time until dose limiting toxicity (DLT) occurred. If no DLT occurred within 28 days (1 cycle), the following group was enrolled into the next dose level. Results: Twenty-three patients with advanced cancers have been treated in this study. All patients have been evaluated for toxicity and response. Eighty cycles of TCT have been administered (1–13 cycles/patient). Patient characteristics: Median age 59 (31–79), PS ECOG 1 (0–2). Type of cancer: renal (7), bladder (2), pancreatic (2), prostate (2), colon (2), and lung, gastric, synovial sarcoma, angiosarcoma, anal, nasopharyngeal, breast, esophageal (1 each). Prior to TCT, all patients had objective documentation of progressive metastatic disease after a median of 2 therapies (range 0–4). Objective response: Four subjects (17%) achieved partial response (renal 1, gastric 1, prostate 2), and 4 patients (17%) had stable disease (renal 1, colon 1, pancreas 2), adding to a clinical benefit of 34%. Toxicity: Treatment was well tolerated. Common toxicities included grade 3 thromboses 17%; and grade 1–2: hand-foot syndrome, fatigue, sensory neuropathy, nausea, vomiting, and neutropenia. Based on DLT within the first 28 days, the MTD of daily TCT therapy was thalidomide 100 mg, capecitabine 2000 mg and temozolomide 100 mg. With long-term treatment, majority of the patients required dose interruptions due to fatigue, hand-foot syndrome, and neutropenia. Dose level 2.5 was implemented: daily thalidomide and 3-weeks-on 1-week-off capecitabine and temozolomide. Six patients were treated at dose level 2.5 without toxicities. Conclusions: TCT is an effective palliative oral chemo-immunotherapy for patients with advanced cancer. The recommended dose for a phase II trial is dose level 2.5, including thalidomide 100 mg daily, capecitabine 2000 mg/day and temozolomide 100 mg/day three-weeks on and one-week off regimen. [Table: see text]
Immunohistochemical analysis of the expression of the human copper transporter hCTR1 in normal and malignant human tissues
Authors: Alison K. Holzer, Nissi Varki, Stephen Howell
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1484 

hCTR1 is the major copper (Cu) influx transporter in human cells. While much is known about the ability of hCTR1 to transport Cu, little is known about the level of expression of this protein in normal and malignant human tissues. This is important with respect to oncology because of the recent finding that hCTR1 is a major determinant of the uptake of cisplatin in human tumor cells (Holzer et al , Mol Pharm 66:817-823, 2004). Cisplatin also regulates the expression of hCTR1 as a 5 minute exposure to cisplatin at concentrations as low as 2 μM reduces the level of endogenous hCTR1 to unmeasurable levels (Holzer et al. , Clin Can Res 10: 6744-6749, 2004). hCTR1 mRNA was previously reported to be detectable in all human tissues examined (Zhou and Gitschier PNAS 94: 7481-8486, 1997). A rabbit polyclonal antibody was developed by immunizing with a peptide from the C-terminal end of hCTR1. After affinity purification this antibody was shown to be specific for hCTR1 using cell lines engineered to alter their expression of hCTR1 and by competition with the immunizing peptide. Using this antibody we undertook an immunohistochemistical analysis of formalin-fixed paraffin-embedded tissues to determine the abundance of hCTR1 in various normal organs and specialized tissues of the body, and representative samples of the major human malignancies. hCTR1 was expressed in several areas of the brain including the cerebral cortex (3/3), meninges (3/3), thalamus (3/3), hippocampus(3/3), choroid plexus (3/3), adrenal medulla (1/1) and autonomic ganglia (4/4). It was also widely expressed in the breast (4/6), in non-neoplastic components of breast carcinomas (7/7) and in the islets of the pancreas (5/5). However, it was not expressed at detectable levels in the non-islet cells of the normal pancreas (0/5), thyroid (0/5), spleen (0/5), prostate (0/7), ovary (0/3), testis (0/5), liver (0/5), kidney (0/5), bronchial epithelium (0/1) or gastrointestinal epithelium (0/3). Consistent with the lack of expression of hCTR1 in the cognate normal tissue, carcinomas of the ovary (0/2) did not exhibit detectable staining. However, despite the lack of expression in the cognate normal tissue, some malignancies of the liver (1/2), kidney (1/2) and colon (1/2) did express hCTR1. hCTR1 was expressed in the majority of breast carcinomas (32/39) and their lymph node metastases (4/6). We conclude that, as detected by immunohistochemical staining, the expression of hCTR1 varies widely among various normal tissues, and that in some cases malignancies that arise from a tissue that does not express hCTR1 display readily detectable staining. This study provides the basis for an analysis of hCTR1 as a biomarker of responsiveness of various types of malignancies to the platinum-containing drugs.
Screening to prevent renal failure in diabetic patients
Authors: K. Borch-Johnsen, C. E. Mogensen, E. Ebbehoj, H. Wenzel, G. Viberti
Journal: BMJ (1996)

Table 1-Students' choice of provider for different sexual health needs.Values are numbers (percentages) Family Sexual Genitourinary planning General health medicine Scenario clinic practitioner clinic clinic Other You want advice on contraception (n = 960) 549 (57) 267 (28) 104 (11) 25 (3) 15 (2) You want free condoms (n = 758)
US device industry and FDA “colluded” on legislation to weaken regulatory oversight
Authors: Jeanne Lenzer
Journal: BMJ (2015)

<h3>Abstract</h3> A characteristic feature of human cognition is our ability to ‘multi-task’ – performing two or more tasks in parallel – particularly when one task is well-learned. How the brain supports this capacity remains poorly understood. Most past studies have focussed on identifying the areas of the brain – typically the dorsolateral prefrontal cortex – that are required to navigate information processing bottlenecks. In contrast, we take a systems neuroscience approach to test the hypothesis that the capacity to conduct effective parallel processing relies on a distributed architecture that interconnects the cerebral cortex with the cerebellum. The latter structure contains over half of the neurons in the adult human brain, and is well-suited to support the fast, effective, dynamic sequences required to perform tasks relatively automatically. By delegating stereotyped within-task computations to the cerebellum, the cerebral cortex can be freed up to focus on the more challenging aspects of performing the tasks in parallel. To test this hypothesis, we analysed task-based fMRI data from 50 participants who performed a task in which they either balanced an avatar on a screen (‘Balance’), performed serial-7 subtractions (‘Calculation’) or performed both in parallel (‘Dual-Task’). Using a set of approaches that include dimensionality reduction, structure-function coupling and time-varying functional connectivity, we provide robust evidence in support of our hypothesis. We conclude that distributed interactions between the cerebral cortex and cerebellum are crucially involved in parallel processing in the human brain.
First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation–Positive Non–Small-Cell Lung Cancer
Authors: Keunchil Park, Chong-Jen Yu, Sang-We Kim, Meng-Chih Lin, Virote Sriuranpong, Chun-Ming Tsai, Jong-Seok Lee, Jin-Hyoung Kang, K. C. Allen Chan, Pablo Perez-Moreno, Peter Button, Myung-Ju Ahn, Tony Mok
Journal: JAMA Oncology (2015)

Continuing molecularly targeted treatment beyond disease progression in non-small-cell lung cancer (NSCLC) has appeared promising in retrospective analyses, highlighting the challenge to identify whether progression is the optimal time to switch treatment.To study the efficacy of first-line erlotinib therapy in patients with NSCLC with activating EGFR mutations and postprogression erlotinib therapy.ASPIRATION (Asian Pacific trial of Tarceva as first-line in EGFR mutation) was a phase 2, open-label, single-arm study conducted from 2011 to 2012 in 23 centers in Hong Kong, Korea, Taiwan, and Thailand of adults with stage IV, EGFR mutation-positive NSCLC, with ECOG performance status 0 to 2.Patients received erlotinib 150 mg/d orally until disease progression, after which erlotinib therapy could be continued at patient and/or investigator discretion.The primary end point was progression-free survival (PFS1; time to Response Evaluation Criteria in Solid Tumours 1.1 progression or death). Secondary end points included PFS2 (time to off-erlotinib progression if erlotinib therapy was extended beyond progression at patient and/or investigator discretion), objective response rate, disease control rate, overall survival, and safety. The use of plasma-based assessment of EGFR mutations was also investigated.Of 359 patients screened, 208 were enrolled. Median follow-up was 11.3 (95% CI, 10.9-13.0) months. Of the 207 intent-to-treat patients (62.3% female; median age, 60.8 [range, 28-89] y), 176 had a PFS1 event (171 progression and 5 deaths); of these, 78 discontinued and 93 continued erlotinib therapy following progression. Median PFS1 was 10.8 (95% CI, 9.2-11.1) months. Median PFS1 and PFS2 in the 93 continuing patients was 11.0 (95% CI, 9.2-11.1) and 14.1 (95% CI, 12.2-15.9) months, respectively. Median PFS1 and PFS2 was 11.0 (95% CI, 9.3-12.0) and 14.9 (95% CI, 12.2-17.2) months in patients with exon 19 deletions or L585R mutations. Overall response rate was 66.2%; disease control rate was 82.6%. Median overall survival was 31.0 months (95% CI, 27.3 months to not reached). In the safety population (n = 207) serious adverse events were reported in 27.1%, with events of at least grade 3 experienced by 50.2%. Sensitivity and specificity of plasma-based EGFR mutation analysis was 77% and 92%, respectively.ASPIRATION supports the efficacy of first-line erlotinib therapy in patients with EGFR mutation-positive NSCLC and that treatment beyond progression is feasible and may delay salvage therapy in selected patients.clinicaltrials.gov Identifier: NCT01310036.
Removing barriers to clinical research in community hospitals—The Fox Chase Cancer Center Partners experience
Authors: M. A. O'Grady, S. J. Cohen, P. A. Keeley, E. Sein, B. J. Miller, P. F. Engstrom
Journal: Journal of Clinical Oncology (2007)

6614 Background: Although the majority of cancer patients are treated in community hospitals, resources to support community clinical trials are often limited. The Fox Chase Cancer Center Partners (FCCCP) initiative is a large academic and community based oncology program in the Delaware Valley. We hypothesized that a detailed clinical research assessment within the 18 main community cancer research programs of the FCCCP would result in improved clinical trial accrual. Methods: The FCCCP clinical team completed research assessments at 10 affiliated community hospitals during 2004–2006 to evaluate active trials, research nurses and data managers, and research barriers. Institutions were benchmarked for staffing, processes, outreach, and quality improvement. Results were presented to administration at each hospital and impact on research accrual recorded. Results: In 2004, 371 patients were treated on clinical trials at 18 FCCCP community research programs. The median number of data managers, research nurses, and open protocols per site was 0.7, 1.6 and 48 respectively. The most common perceived barriers to accrual by investigators and research staff were regulatory burden, time, and awareness. Recommendations included: improved tumor registry identification of clinical trial candidates, increased staffing, improved web-based outreach, and targeted research affiliations. With regulatory burden a significant research barrier, the following IRB streamlining processes were recommended: NCI Central IRB, for-profit IRBs, IRB reciprocity, and centralized health system IRBs. With implementation of recommendations, 10/18 IRBs have transferred to the NCI-Central IRB for phase III cooperative group studies. The median number of data managers and research nurses per site increased to 1.25 and 1.7 respectively. Although the median number of open trials per site remained at 48, accruals to clinical trials increased to 805, representing a 116% increase. Conclusions: Research assessments are feasible in a large academic-community hospital partnership program and result in best practice recommendations with increased clinical trial accrual. Larger scale implementation of research infrastructure in community oncology programs is warranted. No significant financial relationships to disclose.
Incidence of Cancer of the Large Bowel in Women in Relation to Reproductive and Hormonal Factors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: N S Weiss, J R Daling, W H Chow
Journal: JNCI Journal of the National Cancer Institute (1981)

Female residents of King and Pierce Counties (Washington) in whom carcinoma of the colon or rectum was diagnosed during a 15-month period in 1976–77 were interviewed regarding their menstrual and reproductive histories. A random sample of women from the same population was interviewed for comparison. On the average, women with colon cancer had given birth to fewer children than had controls; compared to the incidence of colon cancer in nulliparous women, the incidence in women with 1 or 2 children was reduced by 30%, whereas the incidence in women with 3 or more children was reduced by 50% (P=0.004). No association was present between parity and rectal cancer. Neither contraceptive nor noncontraceptive estrogen use was related to the incidence of colon cancer. Use of oral contraceptives was more common among women with rectal cancer than among controls, but this result could well have arisen by chance (P=0.09). The data were not adequate to determine whether it was the inability to conceive and deliver a child that was related to colon cancer or the failure to undergo the physiologic changes that accompany pregnancy. Nonetheless, the association of low parity with the incidence of colon cancer has now been observed several times, in each instance to a moderately strong degree. This observation suggests that events of reproductive life have a bearing on a woman's subsequent risk of developing colon cancer.
Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?
Authors: Natalie E. Zlebnik, Joseph F. Cheer
Journal: Annual Review of Neuroscience (2016)

The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia. Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders. Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD). Unlike Δ 9 -tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders. Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression. Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.
Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis
Authors: Erin Nevius, Flavia Pinho, Meera Dhodapkar, Huiyan Jin, Kristina Nadrah, Mark C. Horowitz, Junichi Kikuta, Masaru Ishii, João P. Pereira
Journal: The Journal of Experimental Medicine (2015)

Bone surfaces attract hematopoietic and nonhematopoietic cells, such as osteoclasts (OCs) and osteoblasts (OBs), and are targeted by bone metastatic cancers. However, the mechanisms guiding cells toward bone surfaces are essentially unknown. Here, we show that the Gαi protein–coupled receptor (GPCR) EBI2 is expressed in mouse monocyte/OC precursors (OCPs) and its oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-OHC) is secreted abundantly by OBs. Using in vitro time-lapse microscopy and intravital two-photon microscopy, we show that EBI2 enhances the development of large OCs by promoting OCP motility, thus facilitating cell–cell interactions and fusion in vitro and in vivo. EBI2 is also necessary and sufficient for guiding OCPs toward bone surfaces. Interestingly, OCPs also secrete 7α,25-OHC, which promotes autocrine EBI2 signaling and reduces OCP migration toward bone surfaces in vivo. Defective EBI2 signaling led to increased bone mass in male mice and protected female mice from age- and estrogen deficiency–induced osteoporosis. This study identifies a novel pathway involved in OCP homing to the bone surface that may have significant therapeutic potential.