tbuckley/cabot-search huggingface dataset:
Solid Tumors After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study
Authors: Chunkit Fung, Sophie D. Fossa, Michael T. Milano, Jan Oldenburg, Lois B. Travis
Journal: Journal of Clinical Oncology (2013)

Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy.Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up.Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78).To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility.
Abstract P2-01-09: Application of the Z0011 criteria on Dutch breast cancer patients
Authors: Nicole C Verheuvel, Vivianne CG Tjan-Heijnen, Adri C Voogd, Rudi MH Roumen
Journal: Cancer Research (2015)

Abstract Background The American College of Surgeons Oncology Group reported a randomized controlled trial (Z0011-trial) among women with T1-2N0M0 breast cancer treated with breast conserving therapy. It showed that axillary lymph node dissection may be redundant in selected sentinel node positive patients. Though, it raises questions as to the general applicability of these results. Therefore, this study aims to examine the practice changing effect and the clinical relevance of the criteria described in the Z0011 trial, when applied to a Dutch population of patients diagnosed with invasive breast cancer. Methods This is a multicenter study including patients with T1-2N0-1M0 invasive breast cancer treated in either of the 10 different hospitals affiliated with the Dutch National Cancer Registry region South in the period between January 2007 and December 2012. All patients underwent a clinical examination, a mammography and sonographic examination of the breast and the ipsilateral axilla. Chi-square analyses or a Fisher’s exact test were used to assess differences in patient and tumor characteristics the Z0011 population and the Dutch cohort. A p-value of ≤0.05 was considered statistically significant. Results A total of 11,031 patients had invasive breast cancer, of whom 5368 patients were treated with breast conserving therapy. In 6.8% axillary status was determined by the ultrasound guided lymph node biopsy and in 93.1% axillary metastases were found trough the sentinel node procedure after a negative or inconclusive ultrasound. When applying the Z0011 criteria to our study population of node positive patients, 5.7% of all breast cancer patients, equalling 11.8% of patients receiving breast conserving therapy, met the Z0011 criteria. Conclusion These results suggest that when applying the Z0011 criteria to all node positive patients, including patients with a positive sentinel node and patients with a positive ultrasound guided lymph node biopsy, only in 5.7% of all invasive breast cancer patients could be spared an ALND and its morbidity. This is a small practice changing effect. Nevertheless, it is worthwhile to consider implementing the findings of Z0011 trial in daily clinical practice. Citation Format: Nicole C Verheuvel, Vivianne CG Tjan-Heijnen, Adri C Voogd, Rudi MH Roumen. Application of the Z0011 criteria on Dutch breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-09.
Relation Between Kidney Function, Proteinuria, and Adverse Outcomes
Authors: Brenda R. Hemmelgarn
Journal: JAMA (2010)

The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system.To determine the association between reduced GFR, proteinuria, and adverse clinical outcomes.Community-based cohort study with participants identified from a province-wide laboratory registry that includes eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR).All-cause mortality, myocardial infarction, and progression to kidney failure.The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m(2) or greater. Over median follow-up of 35 months (range, 0-59 months), 27 959 participants (3.0%) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60 mL/min/1.73 m(2) or greater, as compared with those with eGFR of 45 to 59.9 mL/min/1.73 m(2) and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs 2.9 [95% CI, 2.7-3.0] per 1000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level.The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
‘Don’t blame the middle man’: an exploratory qualitative study to explore the experiences of translators breaking bad news
Authors: Joanna Prentice, Annmarie Nelson, Jessica Baillie, Hannah Osborn, Simon Noble
Journal: Journal of the Royal Society of Medicine (2014)

Healthcare professionals find breaking bad news difficult and upsetting. Increasing cultural diversity has led to a greater number of patients whose first language differs to that of the healthcare provider, with more patients requiring a translator to facilitate communication. Hospitals often ask non-clinical translators to facilitate breaking bad news. We sought to explore the experiences of translators within a specialist oncology centre.Following ethical and governance approvals, semi-structured interviews were undertaken with five translators recruited from the specialist oncology centre. Interviews were audiotaped and transcribed verbatim. The data were analysed thematically, with major themes and subthemes identified.Outpatient setting of a regional cancer centre.Translators serving a regional cancer centre.Qualitative data identified through thematic analysis.Major themes included the significant emotional impact of translating distressing information, the challenges of accurately conveying information in a culturally congruent format and the need for formal briefing, debriefing and support. Subthemes included feeling guilty for divulging distressing news, being the focus of patients' distress or anger, and feeling in conflict with the patient or family and issues surrounding confidentiality. Translators also felt a strong sense of advocacy for the patients and found encounters with death and dying emotionally challenging.The increasing use of translators in the care of patients with advanced cancer is increasingly resulting in lay people being subject to similar emotional pressures faced by clinical staff, yet without the necessary formal training or support mechanisms that are recommended for clinicians. This exploratory study highlights the training and support needs of non-clinical staff as identifying a unique set of communication challenges faced by translators.
Transcriptional and Nontranscriptional Functions of E2F1 in Response to DNA Damage
Authors: Anup K. Biswas, David G. Johnson
Journal: Cancer Research (2011)

Abstract E2F is a family of transcription factors that regulate the expression of genes involved in a wide range of cellular processes, including cell-cycle progression, DNA replication, DNA repair, differentiation, and apoptosis. E2F1, the founding member of the family, undergoes posttranslational modifications in response to DNA damage, resulting in E2F1 stabilization. In some cases, E2F1 is important for DNA damage–induced apoptosis through the transcriptional activation of p73 and perhaps other proapoptotic target genes. However, in other contexts, E2F1 can stimulate DNA repair and promote survival in response to DNA damage. The E2F1 protein accumulates at sites of both DNA double-strand breaks and UV radiation–induced damage, indicating that E2F1 has a nontranscriptional function at sites of damage. This review summarizes recent progress made in understanding the role of E2F1 in the DNA damage response, including transcription-independent activities that facilitate DNA repair in the context of chromatin. Cancer Res; 72(1); 13–7. ©2011 AACR.
(53) Gorlin's syndrome
Authors: W.F.G. Tucker, C.I. Harrington
Journal: British Journal of Dermatology (1986)

Journal Article (53) Gorlin's syndrome Get access W.F.G. Tucker, Drs, W.F.G. Tucker, Drs Search for other works by this author on: Oxford Academic Google Scholar C.I. Harrington C.I. Harrington Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 95–96, https://doi.org/10.1111/j.1365-2133.1986.tb07748.x Published: 01 July 1986
Cost-effectiveness of Magnetic Resonance (MR) Imaging and MR-guided Targeted Biopsy Versus Systematic Transrectal Ultrasound–Guided Biopsy in Diagnosing Prostate Cancer: A Modelling Study from a Health Care Perspective
Authors: Maarten de Rooij, Simone Crienen, J. Alfred Witjes, Jelle O. Barentsz, Maroeska M. Rovers, Janneke P.C. Grutters
Journal: European Urology (2013)
A phase III randomized, double-blind, placebo-controlled trial of gabapentin in the management of hot flashes in men (N00CB)
Authors: C.L. Loprinzi, A.C. Dueck, B.S. Khoyratty, D.L. Barton, S. Jafar, K.M. Rowland, P.J. Atherton, G.W. Marsa, W.H. Knutson, J.D. Bearden, L. Kottschade, T.R. Fitch
Journal: Annals of Oncology (2009)
Intensive Loading Dose of Trastuzumab Achieves Higher-Than-Steady–State Serum Concentrations and Is Well Tolerated
Authors: Brian Leyland-Jones, Ramon Colomer, Maureen E. Trudeau, Andrew Wardley, Jean Latreille, David Cameron, Ricardo Cubedo, Nedal Al-Sakaff, Andrea Feyereislova, Olivier Catalani, Yumi Fukushima, Michael Brewster, Javier Cortés
Journal: Journal of Clinical Oncology (2009)

PURPOSE Pharmacokinetics (PKs) and safety results from phase II/III trials suggest that, if high trastuzumab serum concentrations are reached early during treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, patients will gain clinical benefit, and the synergistic effects of trastuzumab and chemotherapy will be maximized. This phase I/II study evaluated the PKs, efficacy, and safety of a novel, intensive loading regimen of trastuzumab in women with HER2-positive metastatic breast cancer (MBC). PATIENTS AND METHODS An intensive loading regimen of trastuzumab was given (6 mg/kg intravenously on days 1, 8, and 15 followed by 6 mg/kg every 3 weeks from day 22) to women age 18 years or older with HER2-positive MBC who may have received previous surgery, radiotherapy, and/or chemotherapy. Study medication was continued until disease progression or withdrawal occurred. Results All eligible women (N = 72) received at least one dose of trastuzumab. Median estimated trough concentration of trastuzumab at the end of 3 weeks of the intensive loading regimen (total of 18 mg/kg of trastuzumab administered) of cycle 1 was 119 mg/L, which is higher than steady-state trough concentrations with a conventional weekly or every-3-week regimen (64.9 or 47.3 mg/L, respectively). No new or unexpected adverse events or increased cardiotoxicity were reported during the study. In patients with measurable disease (n = 47), response rate was 23.4%. Median time to progression was 7.7 months (in all patients). CONCLUSION An intensive loading regimen of trastuzumab achieved higher-than-steady-state serum concentrations during cycle 1, was well tolerated, and had a good efficacy profile.
Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study
Authors: Rena C Patel, Maricianah Onono, Monica Gandhi, Cinthia Blat, Jill Hagey, Starley B Shade, Eric Vittinghoff, Elizabeth A Bukusi, Sara J Newmann, Craig R Cohen
Journal: The Lancet HIV (2015)
Case Number 22: An interesting case of herpes zoster in rheumatoid arthritis
Authors: E Campalani
Journal: Annals of the Rheumatic Diseases (2002)

An 82 year old woman with seronegative rheumatoid arthritis was admitted during a flare in her disease. Since diagnosis five years previously her arthritis had been managed with low dose oral corticosteroids at a dose of 10 mg daily.

Shortly after …
Divergent Routes to Oral Cancer
Authors: Keith D. Hunter, Johanna K. Thurlow, Janis Fleming, Paul J.H. Drake, J. Keith Vass, Gabriela Kalna, Des J. Higham, Pawel Herzyk, D. Gordon MacDonald, E. Ken Parkinson, Paul R. Harrison
Journal: Cancer Research (2006)

Abstract Most head and neck squamous cell carcinoma (HNSCC) patients present with late-stage cancers, which are difficult to treat. Therefore, early diagnosis of high-risk premalignant lesions and incipient cancers is important. HNSCC is currently perceived as a single progression mechanism, resulting in immortal invasive cancers. However, we have found that ∼40% of primary oral SCCs are mortal in culture, and these have a better prognosis. About 60% of oral premalignancies (dysplasias) are also mortal. The mortal and immortal tumors are generated in vivo as judged by p53 mutations and loss of p16INK4A expression being found only in the original tumors from which the immortal cultures were derived. To investigate the relationships of dysplasias to SCCs, we did microarray analysis of primary cultures of 4 normal oral mucosa biopsies, 19 dysplasias, and 16 SCCs. Spectral clustering using the singular value decomposition and other bioinformatic techniques showed that development of mortal and immortal SCCs involves distinct transcriptional changes. Both SCC classes share most of the transcriptional changes found in their respective dysplasias but have additional changes. Moreover, high-risk dysplasias that subsequently progress to SCCs more closely resemble SCCs than nonprogressing dysplasias. This indicates for the first time that there are divergent mortal and immortal pathways for oral SCC development via intermediate dysplasias. We believe that this new information may lead to new ways of classifying HNSCC in relation to prognosis. (Cancer Res 2006; 66(15): 7405-13)
Bone marrow transplant nephropathy
Authors: D N Cruz, M A Perazella, R L Mahnensmith
Journal: Journal of the American Society of Nephrology (1997)

Bone marrow transplantation can be complicated by renal failure resulting from a variety of causes. Early renal injury most often results from infection and its subsequent treatment with nephrotoxic medications. Late renal injury after bone marrow transplantation is characterized by a syndrome similar to the hemolytic uremic syndrome. This renal syndrome, called "bone marrow transplant nephropathy," is thought to evolve from the late effects of radiation therapy and cytotoxic chemotherapy on the kidney. In this article, a case of bone marrow transplant nephropathy and a review of the clinical and pathologic features are presented.
Isolated CNS Relapse in Human Epidermal Growth Factor Receptor 2–Positive Esophagogastric Cancer: Effective Treatment With Trastuzumab After Failure of Surgery and Radiotherapy
Authors: Tom Geldart, George Astras
Journal: Journal of Clinical Oncology (2011)

A 44-year-old man initially presented in August 2008 with iron-deficiency anemia and dysphagia to solids.Endoscopy, endoscopic ultrasound, computed tomography (CT), positron emission tomography-CT, and laparoscopy confirmed stage T3N1M0, type 3, moderately differentiated adenocarcinoma of the esophagogastric junction.He was treated with perioperative chemotherapy within the NCRI (National Cancer Research Institute) ST03 trial, receiving six cycles (three preoperative and three postoperative) of epirubicin, cisplatin, and capecitabine.Preoperative (postneoadjuvant chemotherapy) CT imaging confirmed good response to chemotherapy, and in January 2009, he underwent Ivor Lewis esophagogastrectomy. Postoperative histology confirmed significant pathologic downstaging after chemotherapy, with final histology confirmed as ypT1N0Mx (zero of 51 nodes resected) moderately differentiated adenocarcinoma.There was no evidence of lymphovascular invasion, and all margins were clear of tumor (R0).He remained well until late March 2010, when he developed severe headaches while on a skiing holiday.Brain CT scan confirmed a 5-cm solitary right frontal brain metastasis with associated edema.CT findings were confirmed on magnetic resonance imaging (MRI).CT chest, abdomen, and pelvis and whole-body positron emission tomography-CT revealed no evidence of extracranial metastatic disease.He subsequently underwent image-guided craniotomy and neurosurgical metastectomy.Histopathology confirmed metastatic adenocarcinoma consistent with relapse from his previously diagnosed esophagogastric primary.He was subsequently treated with postoperative whole-brain radiotherapy to a dose of 30 Gy in 10 fractions.In September 2010, he presented with a generalized seizure.CT and subsequent MRI revealed substantial intracranial recurrence at the site of previous surgery, with leptomeningeal and subcutaneous extension of tumor at the site of his craniotomy incision.CT chest, abdomen, and pelvis once again revealed no evidence of extracranial recurrence.Neither further neurosurgical resection nor high-dose palliative radiotherapy was felt to be technically feasible, and he was referred back for consideration of palliative chemotherapy.Between September 29, 2009, and November 24, 2009, he received two cycles of palliative epirubicin, oxaliplatin, and capecitabine chemotherapy.His symptoms did not improve, and he developed worsening headache and increasing steroid dependence.Follow-up MRI scan revealed progressive disease.Further analysis of his resected brain metastasis confirmed strong human epidermal growth factor receptor 2 (HER2) expression (im-
Interleukin-25 As a Novel Therapeutic Target in Nasal Polyps of Chronic Rhinosinusitis
Authors: Dong-Kyu Kim, Hyun-Woo Shin, Min-Hyun Park, Kyung Mi Eun, Mingyu Lee, Daeho So, I.G. Kong, Ji-Hun Mo, Min-Suk Yang, Hong Ryul Jin, Jong-Wan Park, Dae Woo Kim
Journal: Journal of Allergy and Clinical Immunology (2015)
LUMPY: a probabilistic framework for structural variant discovery
Authors: Ryan M Layer, Colby Chiang, Aaron R Quinlan, Ira M Hall
Journal: Genome biology (2014)

Comprehensive discovery of structural variation (SV) from whole genome sequencing data requires multiple detection signals including read-pair, split-read, read-depth and prior knowledge. Owing to technical challenges, extant SV discovery algorithms either use one signal in isolation, or at best use two sequentially. We present LUMPY, a novel SV discovery framework that naturally integrates multiple SV signals jointly across multiple samples. We show that LUMPY yields improved sensitivity, especially when SV signal is reduced owing to either low coverage data or low intra-sample variant allele frequency. We also report a set of 4,564 validated breakpoints from the NA12878 human genome. https://github.com/arq5x/lumpy-sv.
Association Between Acculturation Modes and Type 2 Diabetes Among Native Hawaiians
Authors: Joseph Keawe‘aimoku Kaholokula, Andrea H. Nacapoy, Andrew Grandinetti, Healani K. Chang
Journal: Diabetes Care (2008)

OBJECTIVE—To examine the association between acculturation modes (integrated, assimilated, traditional, and marginalized) and type 2 diabetes prevalence in Native Hawaiians. RESEARCH DESIGN AND METHODS—Cross-sectional data were analyzed from 495 Native Hawaiians, including acculturation modes, diabetes status, triglycerides, fasting insulin, BMI, age, and education level. Acculturation modes were assessed using an eight-item cultural affiliation questionnaire. RESULTS—Native Hawaiians in a traditional mode of acculturation were more likely to have type 2 diabetes (27.9%) than those in integrated (15.4%), assimilated (12.5%), or marginalized (10.5%) modes. CONCLUSIONS—The higher prevalence of type 2 diabetes among Native Hawaiians in a traditional mode of acculturation could not be attributed to any of the sociodemographic or biological factors included in this study. We discuss the role of psychosocial factors as possible mediators in the relationship between acculturation modes and type 2 diabetes.
Prospects for Tuberculosis Elimination
Authors: Christopher Dye, Philippe Glaziou, Katherine Floyd, Mario Raviglione
Journal: Annual Review of Public Health (2012)

The target for TB elimination is to reduce annual incidence to less than one case per million population by 2050. Meeting that target requires a 1,000-fold reduction in incidence in little more than 35 years. This can be achieved only by combining the effective treatment of active TB—early case detection and high cure rates to interrupt transmission—with methods to prevent new infections and to neutralize existing latent infections. Vigorous implementation of the WHO Stop TB Strategy is needed to achieve the former, facilitated by the effective supply of, and demand for, health services. The latter calls for new technology, including biomarkers of TB risk, diagnostics, drugs, and vaccines. An important milestone en route to elimination will be reached when there is less than 1 TB death per 100,000 population, marking entry into the elimination phase. This landmark can be reached by many countries within 1–2 decades.