tbuckley/cabot-search huggingface dataset:
Skin cancer surveillance practices and attitudes among hairdressers: A cross-sectional study in Atlanta, Georgia
Authors: David C. Gibbs, Spencer Ng, Marissa L.H. Baranowski, Sampreet Reddy, Annelise Bederman, Marta B. Bean, Rachel Eisenstadt, Suephy C. Chen
Journal: Journal of the American Academy of Dermatology (2019)
Evaluating the value of checkpoint inhibitor therapy using the ASCO and ESMO frameworks.
Authors: Sophie Feng, Yanshuo Cao, Eitan Amir, Eric Xueyu Chen
Journal: Journal of Clinical Oncology (2019)

17 Background: The advent of checkpoint inhibitor therapy (CIT) has dramatically changed the oncology landscape, but is associated with significant costs. A positive randomized clinical trial (RCT) may not translate to meaningful outcomes for patients. The American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) have developed frameworks to quantify the value of cancer treatment. We applied these frameworks to RCTs involving CIT in order to explore the relationship between trial outcomes and magnitude of clinical benefit. Methods: A literature search was conducted to identify CIT RCTs. Data extracted included study characteristics, pre-specified estimated hazard ratios (eHR) and observed HR (oHR). ASCO Value Framework version 2016 and ESMO Magnitude of Clinical Benefit (MCB) scale v1.1 were applied to each publication by 2 authors independently. Results: 30 RCTs (3 adjuvant, and 27 advanced setting) using CIT were identified between January 2010- October 2018. The majority of trials were in lung cancer (37%) and melanoma (36%). The eHR was 0.71±0.06 (range: 0.55-0.78), and oHR was 0.76±0.15 (range: 0.49 – 1.11). 54% RCTs did not achieve eHR, with a difference of 0.16±0.12 (range: 0.01 – 0.41). ASCO framework scores ranged -24.0 to 71.3, far below the maximum potential score of 180. 18 RCTs formed the basis for FDA approvals. The mean ASCO framework score was 45.6 ± 16.6 (range: 14.4 - 71.3) for FDA approved indications, and 14.0 ± 18.4 (range: -24 – 49) for non-FDA approvals (p &lt; 0.001). All FDA approvals scored grade 4 or 5 on the ESMO MCB scale, indicating a meaningful clinical benefit. Many non-FDA approved RCTs did not receive an MCB grade as they were negative trials. There was no difference in the ASCO framework scores between MCB grade 4 and 5 RCTs. 3 adjuvant RCTs had an ASCO framework score ranging from 20.5 to 38.7 despite an MCB Grade A. Conclusions: Many trials did not meet the pre-specified eHR. FDA approval had statistically significantly higher NHB scores than non-FDA approvals, and they were deemed to have a meaningful clinical benefit according to the ESMO MCB scale. ASCO framework scores may require re-calibration since the highest score achieved in CIT RCTs was only 40% of the maximum score.
Comparison of screening strategies for Lynch syndrome in patients with newly diagnosed endometrial cancer: a prospective cohort study in China
Authors: Xiaopei Chao, Lei Li, Ming Wu, Shuiqing Ma, Xianjie Tan, Sen Zhong, Yalan Bi, Jinghe Lang
Journal: Cancer Communications (2019)

Abstract Background The prevalence of Lynch syndrome and screening strategies for this disorder in Chinese patients with endometrial cancer have seldom been investigated. Such data would be essential for the screening, prevention, genetic counseling, and treatment of Lynch syndrome. The purpose of this prospective study was to determine the accuracy of the mismatch repair (MMR) protein immunohistochemistry (IHC), microsatellite instability (MSI) test, and clinical diagnostic criteria in screening for Lynch syndrome‐associated endometrial cancer (LS‐EC) in a prospective Chinese cohort. Methods All patients with newly diagnosed endometrial cancer (EC) were evaluated using clinical diagnostic criteria (Amsterdam II criteria and the revised Bethesda guidelines), MSI test, and IHC of MMR proteins in tumor tissues. For all patients, the screening results were compared with results of germline sequencing for pathogenic variants of MMR genes. Results Between December 2017 and August 2018, a total of 111 unselected patients with newly diagnosed EC were enrolled. Six patients (5.4%) harbored a pathogenic germline mutation of MMR genes: 1 had a mutation in MutL homolog 1 ( MLH1 ), 2 in MutS homolog 2 ( MSH2 ), and 3 in MutS homolog 6 ( MSH6 ). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying LS‐EC were 33.3%, 88.6%, 14.3%, and 95.9%, for the clinical criteria, 66.7%, 75.0%, 14.3%, and 97.3% for IHC of MMR proteins, 100%, 89.9%, 33.3%, and 100% for MSI test, and 100%, 72.4%, 20.0% and 100% for combined IHC and MSI test, respectively. The combination of IHC and MSI test had higher sensitivity and PPV than the clinical criteria ( p = 0.030). MSI test and IHC were highly concordant for LS‐EC screening (73/77, 94.8%). Conclusion The accuracy of the combination of IHC of MMR proteins and MSI test for screening LS among Chinese patients with EC was superior to that of the clinical criteria. Trial registration NCT03291106. Registered on September 25, 2017
Abstract 80: Interplay Between Cell-cell and Cell-extracellular Matrix Forces Regulate Myocardial Proliferation
Authors: Caimei Zhang, Glenn Radice
Journal: Circulation Research (2017)

Changes in expression and distribution of integrin, fibronectin (FN), and N-cadherin in the postnatal heart accompany the switch from hyperplastic to hypertrophic growth. As FN decreases after birth, N-cadherin/catenin complex accumulates at the cell termini creating a specialized type of cell-cell contact called the intercalated disc (ID). Integrin-FN interactions promote cardiomyocyte and cardiac progenitor cell proliferation. However, little is known regarding the reciprocity between integrin and N-cadherin adhesions in the regulation of myocardial proliferation. Alpha-catenins function as mechanosensors and transduce the intercellular force from N-cadherin to the actin cytoskeleton. To investigate mechanotransduction in the heart, we generated cardiac-specific αE- and αT-catenins double knockout (DKO) mice. The relationship between N-cadherin, integrin, and FN was examined at postnatal day (P) 4, P7, P14, and P60. DKO hearts exhibited aberrant N-cadherin expression accompanied by increased expression of α5/β1 integrin, the primary receptor for FN. Normally found at the lateral membrane, α5 and FN accumulated at the ID along with N-cadherin in DKO hearts. FN-integrin binding leads to the formation of FN fibrils that are initially soluble in the detergent deoxycholate (DOC) but are gradually converted into a stable, DOC-insoluble form that comprises the mature matrix. Both α5 and FN were increased in the DOC-insoluble fraction consistent with enhanced matrix assembly in DKO hearts. Activation of focal adhesion kinase (FAK) and p130CAS were observed in the DKO hearts consistent with increased cell-extracellular matrix interactions. Complementary experiments performed with deformable substrata demonstrated that stiffness-mediated Yap nuclear accumulation was dependent on FAK activity. These data demonstrate that α-catenins regulate the balance between cell-cell and cell-matrix adhesions, which, in turn, controls Yap subcellular localization, thus providing a molecular explanation for loss of regenerative potential in the adult heart.
Authors response: giant oversights in the human gut virome
Authors: Tao Zuo, Siew C Ng
Journal: Gut (2019)

We explored gut mucosal virome alterations in UC1 and appreciate the insightful comments from the authors who highlighted some of the important limitations of human gut virome studies.2 Unlike the bacteria microbiome, the gut virome remains largely underexplored. There is currently no gold standard on the optimal pipelines or methods for virome analysis. In addition, the lack of consensus in both methodology and virus taxonomy classification underscores significant limitations and challenges in virome metagenomics analysis.3 4 

Most metagenomic studies of the human gut virome have adopted practical methods based on filtration with subsequent precipitation or ultrafiltration of virus-like particles (VLPs).3 Such protocols including that of ours can introduce considerable amounts of residual DNA into the samples, such as …
Oral Contraceptives and Cardiovascular Disease
Authors: Bruce V. Stadel
Journal: New England Journal of Medicine (1981)

Myocardial Infarction and StrokeIt is now established that in addition to increasing the risk of venous thromboembolic disease, oral contraceptives increase the risks of myocardial infarction, thrombotic stroke, and hemorrhagic stroke.11 (Some recent data suggest that oral contraceptives may also increase the risk of other forms of cardiovascular disease,17 but the findings are inconclusive and are therefore not considered in this review.) Vital statistics and epidemiologic studies in Great Britain and the United States show that among nonpregnant women of reproductive age who are not using oral contraceptives, the risks of myocardial infarction and stroke (of both categories) increase . . .
Ian Craft: fertility pioneer responsible for the UK’s first IVF twins
Authors: Penny Warren
Journal: BMJ (2019)

Credit: Simon Craft

On 29 April 1982, Europe’s first set of twins conceived by in vitro fertilisation (IVF) were born at London’s Royal Free Hospital. They represented the culmination of five years’ work for Ian Craft, professor of obstetrics and gynaecology.

Helped by a donation from Pink Floyd’s Roger Waters, in 1977 Craft had set up an IVF facility at the Royal Free. After the twins’ birth, he had a succession of “IVF firsts.” In 1984, he co-wrote a seminal paper on the use of buserelin to solve the problem of women ovulating before their eggs could be collected, and in 1985 he achieved the first birth with the drug. Buserelin’s use alone would double the rate of live births.

In 1986, Craft was the first in the UK to achieve a live birth through gamete intrafallopian transfer, and in 1987 he was the first to help a woman have a baby through egg donation. In the same …
Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer
Authors: Andrew Woolston, Khurum Khan, Georgia Spain, Louise J. Barber, Beatrice Griffiths, Reyes Gonzalez-Exposito, Lisa Hornsteiner, Marco Punta, Yatish Patil, Alice Newey, Sonia Mansukhani, Matthew N. Davies, Andrew Furness, Francesco Sclafani, Clare Peckitt, Mirta Jiménez, Kyriakos Kouvelakis, Romana Ranftl, Ruwaida Begum, Isma Rana, Janet Thomas, Annette Bryant, Sergio Quezada, Andrew Wotherspoon, Nasir Khan, Nikolaos Fotiadis, Teresa Marafioti, Thomas Powles, Stefano Lise, Fernando Calvo, Sebastian Guettler, Katharina von Loga, Sheela Rao, David Watkins, Naureen Starling, Ian Chau, Anguraj Sadanandam, David Cunningham, Marco Gerlinger
Journal: Cancer Cell (2019)

Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF1 and non-canonical RAS/RAF aberrations with primary resistance and validated transcriptomic CRC subtypes as non-genetic predictors of benefit. Sixty-four percent of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype at baseline to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PD-L1 and LAG3 immune checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy.
ZEBRA: an ACCRU/IRCI multicenter phase 2 study of pembrolizumab in patients with advanced small bowel adenocarcinoma (SBA)
Authors: K. Pedersen, N. Foster, M. Overman, P. Boland, S. Kim, K. Arrambide, B. Jaszewski, J. Welch, R. Wilson, R. McWilliams
Journal: Annals of Oncology (2019)
Abstract 12532: Atrial Fibrillation and Left Ventricular Dilatation as Risk Factors for Newly Developed Mitral Regurgitation after Cardiac Resynchronization Therapy: Impact on Outcome
Authors: Tetsuari Onishi, Toshinari Onishi, Josef Marek, Mohamed Ahmed, David Schwartzman, John Gorcsan
Journal: Circulation (2012)

Background: Cardiac resynchronization therapy (CRT) is associated overall with reduction in mitral regurgitation (MR). However, an important subset of patients have newly developed significant MR a...
Analysis of renal function in patients entered onto CTEP-sponsored phase I studies since 1979
Authors: W. M. McHayleh, R. Sehgal, D. M. Potter, R. B. Royds, T. G. Nekrassova, S. P. Ivy, S. Ramalingam, C. P. Belani, C. L. Naret, M. J. Egorin
Journal: Journal of Clinical Oncology (2007)

2519 Background: The NCI and FDA utilize different criteria for classifying renal dysfunction. We analyzed renal function in all patients entered onto CTEP-sponsored phase I clinical trials since 1979 to evaluate the percentage of patients with acceptable renal function according to criteria utilized by the National Cancer Institute, as compared with those advocated by the Food and Drug Administration. Methods: Data from 12575 patients entered onto CTEP-sponsored phase I studies since 1979 were evaluated. Renal function was characterized by calculating creatinine clearance (CrCl) by three different formulae (Cockroft-Gault, Jelliffe, and Levey), as well as GFR according to MDRD. Results: Of the 12,575 patients, data were available to calculate renal function with all the 4 formulae in 5,177. Distributions of CrCl and GFR were defined, and patients were classified as having normal renal function or severe, moderate, or mild renal dysfunction according to FDA or NCI criteria. The resulting distributions are indicated in the table below. Conclusions: Approximately 40% of patients entered into CTEP-sponsored phase I trials have mild renal dysfunction according to FDA criteria and approximately 95% have CrCls &gt; 50 ml/min. These data imply that moderate and severe are the only renal dysfunction categories that need to be evaluated in renal dysfunction studies of novel antineoplastic agents and that FDA guidelines should be applicable. Whether patients in the NCI database with CrCls of 50–80 ml/min experience more toxicities than those with creatinine clearances &gt; 80 ml/min is undergoing evaluation. [Table: see text] [Table: see text]
Factors associated with over and underuse of response evaluation in elderly myeloma patients.
Authors: Siyang Leng, Suzanne Lentzsch, Yizhen Chen, Divaya Bhutani, Jason Dennis Wright, Melissa Kate Accordino, Dawn L. Hershman, Alfred I. Neugut
Journal: Journal of Clinical Oncology (2019)

e19518 Background: Most patients with multiple myeloma (MM) have detectable monoclonal protein. While guidelines do not specify the frequency of lab testing for response evaluation, most MM clinical trials perform monthly assessment. We examined the use of 4 serologic tests – protein electrophoresis (SPEP), immunofixation (IFE), quantitative immunoglobulins (QIG), and free light chain (FLC) in newly-diagnosed MM patients. Methods: We identified patients age ≥65 with MM (ICD-O 34000) in the Surveillance, Epidemiology and End Results (SEER)-Medicare database from 2000-2013. Patients were required to have bone marrow biopsy within 6 months of diagnosis, and taken chemotherapy approved for MM. Use of a test was defined as having ≥1 instance of its CPT code within 12 months of diagnosis. Patients with &gt; 12 instances were defined as overusers. Multiple instances of a test on the same date were counted once. Multivariable logistic regression models using covariates including: age and year at MM diagnosis, race, marital status, Charlson comorbidity, chemotherapy use, number of hospitalizations and oncology office visits within 12 months of diagnosis, were developed to examine associations with overuse. Results: Among 6,214 identified patients, users were: SPEP 5,532 (89%), IFE 4,745 (76%), QIG 5,524 (89%), and FLC 3,864 (62%). The median (interquartile range) times each test was used in the first year following diagnosis were: SPEP 6 (3-10), IFE 3 (2-7), QIG 6 (3-10), FLC 5 (2-9). The numbers of overusers were: SPEP 721 (13%), IFE 265 (6%), QIG 498 (9%), FLC 350 (9%). 231 (4%) patients were overusers of 2 tests. Factors associated with overuse common to all 4 tests were: younger age at diagnosis (eg, SPEP: odds ratio (OR) 2.0 for aged 65-74 vs ≥85; P &lt; .001), more oncology office visits (eg, QIG: OR 2.2 for &gt; 15 vs 0-6; P &lt; .001), and use of combination chemotherapy (eg, SPEP: OR 2.2 for proteasome inhibitor + immunomodulatory drug (IMID) vs those on IMID ; P &lt; .001). Conclusions: In our Medicare population, patients on average underwent response evaluation much less often than monthly, but we also found overuse. Further investigation of the use of these tests is warranted given their central importance to MM care and their cumulative financial cost.
Infographic. New Zealand rugby’s community concussion initiative: keeping kiwi communities RugbySmart
Authors: Danielle Salmon, John Sullivan, Janelle Romanchuk, Ian Murphy, Simon Walters, Chris Whatman, Amanda Clacy, Sierra Keung, Klazina Van Der Vis
Journal: British Journal of Sports Medicine (2019)

Rugby union (rugby) is a popular full-contact team sport played by 8.5 million individuals in 121 countries across the globe (https://www.world.rugby/development/player-numbers). In New Zealand (NZ), rugby is played by 157 218 individuals and engages all genders, ethnicities and socioeconomic diversities throughout the population. A key focus of both the international governing body of rugby (World Rugby) and NZ rugby (NZR) is the improvement of player welfare around common injuries such as concussion. Informed by the guidelines developed following the 2016 Berlin Concussion Consensus,1 World Rugby has developed policies and education programmes to standardise concussion management and promote …
FDG-PET/CT Demonstrates Splenic Angiosarcoma Bone Marrow Metastasis
Authors: Hiroaki Takahashi, Tadashi Hara, Hideo Suzuki, Ryosuke Hashimoto, Manabu Minami
Journal: Clinical Nuclear Medicine (2019)

Abstract Some patients with splenic angiosarcoma initially manifest thrombocytopenia owing to hypersplenism or tumor-related bone marrow fibrosis. The diagnosis of bone marrow metastasis in patients with splenic angiosarcoma is challenging, as the presentation mimics idiopathic thrombocytopenic purpura or primary myelofibrosis. Our case showed diffuse FDG uptake in the vertebral bodies, sacroiliac bone, humerus, femur, and clavicles. It was pathologically diagnosed as bone marrow metastasis of splenic angiosarcoma. We believe that the heterogeneous FDG accumulation in the bone marrow, although nonspecific, can be useful for the diagnosis of the bone marrow metastasis in patients with splenic angiosarcoma.
Numerous published biomarker prognostic models for heart failure exist, but none is officially recommended in clinical guidelines:a paradox or a research scandal/failure?
Authors: N Kadoglou, M Vazquez Montes, K Taylor, R Perera, N Jones, B Speich, N Roberts, G Collins, Hobbs Fdr., C Taylor, K Moons, T Debray, J Parissis, M Trivella
Journal: European Journal of Heart Failure (2019)
Comparison of salvage therapies for relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Network meta-analysis.
Authors: Venkata Vosuri, Ravi Kaisreddy, Somasekhar Bandi
Journal: Journal of Clinical Oncology (2019)

e19037 Background: Salvage chemotherapy followed by autologous stem cell transplantation(ASCT) is the standard second-line treatment for relapsed or refractory diffuse large b-cell lymphoma(DLBCL). Rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE) and rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP) are the two widely used regimens worldwide but quest for optimal regimen continues. Our objective is to compare currently available salvage therapies based on complete response and adverse events. Methods: Pubmed, EMBASE and Clinicaltrials.gov were queried for salvage therapies in relapsed or refractory DLBCL. Only randomized clinical trials including phase 2 and 3 trials involving salvage therapies for relapsed or refractory DLBCL were selected. Data was extracted based on meta-analysis guidelines by two independent reviewers. Network meta-analyses of treatment effects and adverse outcomes were calculated with a frequentist approach. Results: Overall, 5 studies(1480 patients) were included. The salvage therapies investigated were rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE), rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP), rituximab plus gemcitabine, dexamethasone, cisplatin(R-GDP), ofatumumab plus dexamethasone, cytarabine, and cisplatin(O-DHAP), ifosfamide plus ofatumunab, carboplatin, and etoposide(O-ICE), dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide(DR-ICE). Of the 6 regimens in the network, treatment with R-DHAP (OR:0.36,95%CI:0.24-0.54), R-GDP(OR:0.37,95%CI: 0.21-0.65), O-ICE(OR:0.16,95%CI: 0.05-0.53), O-DHAP(OR:0.30,95%CI:0.17-0.52), DR-ICE(OR:0.77,95%CI:0.40-1.49) were not superior against network placebo(R-ICE) in achieving complete response. Higher odds of occurring severe adverse events was observed in R-DHAP(OR:2.02,95%CI: 1.35-3.01) and O-DHAP(OR:2.15,95%CI: 1.24-3.72) salvage regimens when compared to R-ICE. Conclusions: R-DHAP, R-GDP, O-ICE and O-DHAP were found to have no difference in treatment effect in achieving complete response in comparison to R-ICE. R-DHAP and O-DHAP are associated with higher number of severe adverse events in comparison with R-ICE. Outcomes mentioned above should be interpreted in the context of drugs and other factors involved in the disease.
Potential involvement of OX40 in the regulation of autoantibody sialylation in arthritis
Authors: Izumi Kurata, Isao Matsumoto, Ayako Ohyama, Atsumu Osada, Hiroshi Ebe, Hoshimi Kawaguchi, Shunta Kaneko, Yuya Kondo, Hiroto Tsuboi, Azusa Tomioka, Hiroyuki Kaji, Takayuki Sumida
Journal: Annals of the Rheumatic Diseases (2019)

An increased proportion of circulating follicular helper T (Tfh) cells was reported in rheumatoid arthritis (RA), but it remains uncertain how Tfh cells affect antibody hyposialylation. We investigated the regulation of autoantibody hyposialylation by Tfh cells in RA using murine model.Behaviours of Tfh cells and their function on B cell promotion were analysed. Change of arthritogenicity and sialylation of autoantibodies during the course of arthritis was examined by mass spectrometry. Tfh-mediated regulation of hyposialylation was investigated, and the responsible cell surface molecule was specified both in vitro and in vivo. The relation between circulating Tfh cells and hyposialylation was analysed in patients with RA.An increase in Tfh, particularly interleukin-17 producing Tfh (Tfh17) cells, at the onset of arthritis and their enhancement of autoantibody production were found. Autoantibodies at the onset phase demonstrated stronger inflammatory properties than those at the resolution phase, and mass spectrometric analysis revealed their difference in sialylation. In vitro coculture showed enhanced hyposialylation by the Tfh cells via OX40, which was highly expressed in the Tfh and Tfh17 cells. Blockade of OX40 prevented the development of arthritis with reduction in Tfh17 cells and recovery of autoantibody sialylation. Analysis of patients with RA showed abundance of OX40-overexpressing Tfh17 cells, and their proportion correlated negatively with the expression of α2,6-sialyltransferase 1, an enzyme responsible for sialylation.OX40 expressed on Tfh cells can regulate autoantibody sialylation and play a crucial role in the development of autoimmune arthritis.