tbuckley/cabot-search huggingface dataset:
Hyperspectral Imaging for Resection Margin Assessment during Cancer Surgery
Authors: Esther Kho, Lisanne L. de Boer, Koen K. Van de Vijver, Frederieke van Duijnhoven, Marie-Jeanne T.F.D. Vrancken Peeters, Henricus J.C.M. Sterenborg, Theo J.M. Ruers
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Complete tumor removal during cancer surgery remains challenging due to the lack of accurate techniques for intraoperative margin assessment. This study evaluates the use of hyperspectral imaging for margin assessment by reporting its use in fresh human breast specimens. Experimental Design: Hyperspectral data were first acquired on tissue slices from 18 patients after gross sectioning of the resected breast specimen. This dataset, which contained over 22,000 spectra, was well correlated with histopathology and was used to develop a support vector machine classification algorithm and test the classification performance. In addition, we evaluated hyperspectral imaging in clinical practice by imaging the resection surface of six lumpectomy specimens. With the developed classification algorithm, we determined if hyperspectral imaging could detect malignancies in the resection surface. Results: The diagnostic performance of hyperspectral imaging on the tissue slices was high; invasive carcinoma, ductal carcinoma in situ, connective tissue, and adipose tissue were correctly classified as tumor or healthy tissue with accuracies of 93%, 84%, 70%, and 99%, respectively. These accuracies increased with the size of the area, consisting of one tissue type. The entire resection surface was imaged within 10 minutes, and data analysis was performed fast, without the need of an experienced operator. On the resection surface, hyperspectral imaging detected 19 of 20 malignancies that, according to the available histopathology information, were located within 2 mm of the resection surface. Conclusions: These findings show the potential of using hyperspectral imaging for margin assessment during breast-conserving surgery to improve surgical outcome.
Characterizing discontinuation and withdrawal from phase III oncology clinical trials.
Authors: Navraj Malhi, Gillian Gresham, Bernhard J. Eigl, Janice Grant, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2015)

e17731 Background: Clinical trials are essential to the evaluation of novel interventions, but the integrity of these studies can be compromised if participants discontinue or withdraw from the trials prematurely due to unanticipated causes. Our aims were to determine the factors associated with increased risk of early dropout and devise a scoring system to stratify trial participants into different risk categories. Methods: Consecutive patients enrolled in phase III oncology clinical trials of major solid tumors at any 1 of 5 cancer centers in British Columbia from 1999 to 2013 were included for review. Time-to-event analyses were conducted with time to trial dropout (TTD) as the primary outcome, defined as discontinuation or withdrawal from study due to reasons other than lack of response, recurrent/progressive disease, or death. Multivariate analyses were performed to identify factors associated with TTD. Regression coefficients were used to devise and validate a weighted scale which assigned scores to patient groups based on their risk for early trial dropout. Results: We identified 1,002 patients: median age was 58 years, 32% were men, 90% had ECOG 0 or 1, and 53% / 20% / 16% / 11% participated in breast / gastrointestinal / genitourinary / lung cancer trials, respectively. In the entire cohort, dropout was prevalent (20%), of which one-third occurred within 6 months of trial enrollment. Across the tumor groups, discontinuation was most commonly due to toxicities (25%) and the decision to withdraw from study was made by physicians in 70% of cases. In comparison, dropout occurred most frequently among lung (82%) and least frequently (28%) among breast trial participants. Tumor-specific weighted scoring systems were successfully derived that classified patients into low, moderate, and high risk groups for dropout. C-statistics ranged from 0.69 to 0.82 indicating good discrimination of the models. Advanced disease (p < 0.01) and ECOG 2+ (p < 0.01) consistently predicted for earlier TTD. Conclusions: Dropout from clinical trials is common, mainly attributable to toxicities. Effective risk stratification of potential study participants prior to enrollment may optimize patient selection and enhance the internal validity of trials.
Parallel Speciation of Wild Rice Associated with Habitat Shifts
Authors: Zhe Cai, Lian Zhou, Ning-Ning Ren, Xun Xu, Rong Liu, Lei Huang, Xiao-Ming Zheng, Qing-Lin Meng, Yu-Su Du, Mei-Xia Wang, Mu-Fan Geng, Wen-Li Chen, Chun-Yan Jing, Xin-Hui Zou, Jie Guo, Cheng-Bin Chen, Hua-Zhong Zeng, Yun-Tao Liang, Xing-Hua Wei, Ya-Long Guo, Hai-Fei Zhou, Fu-Min Zhang, Song Ge
Journal: Molecular Biology and Evolution (2019)

The occurrence of parallel speciation strongly implies the action of natural selection. However, it is unclear how general a phenomena parallel speciation is since it was only shown in a small number of animal species. In particular, the adaptive process and mechanisms underlying the process of parallel speciation remain elusive. Here, we used an integrative approach incorporating population genomics, common garden, and crossing experiments to investigate parallel speciation of the wild rice species Oryza nivara from O. rufipogon. We demonstrated that O. nivara originated multiple times from different O. rufipogon populations and revealed that different O. nivara populations have evolved similar phenotypes under divergent selection, a reflection of recurrent local adaptation of ancient O. rufipogon populations to dry habitats. Almost completed premating isolation was detected between O. nivara and O. rufipogon in the absence of any postmating barriers between and within these species. These results suggest that flowering time is a "magic" trait that contributes to both local adaptation and reproductive isolation in the origin of wild rice species. Our study thus demonstrates a convincing case of parallel ecological speciation as a consequence of adaptation to new environments.
Expression of lymphocyte-activating gene 3 and T-cell immunoreceptor with immunoglobulin and ITIM domains in cutaneous melanoma and their correlation with programmed cell death 1 expression in tumor-infiltrating lymphocytes
Authors: Woo Jin Lee, Ye Jin Lee, Myoung Eun Choi, Kyung A. Yun, Chong Hyun Won, Mi Woo Lee, Jee Ho Choi, Sung Eun Chang
Journal: Journal of the American Academy of Dermatology (2019)
Risk for vascular thromboembolic events (VaTEs) in patients (pts) with advanced urinary tract cancer (aUTC) treated with chemotherapy.
Authors: Aristotelis Bamias, George Tsironis, Ioannis Dimitriadis, Kimon Tzanis, Anna Tsiara, Aikaterini Xirokosta, Maria Kaparelou, Anastasios Kyriazoglou, Abis Cohen, Despoina Barbarousi, Konstantinos Koutsoukos, Michael Liontos, Roubini Zakopoulou, Euthymios Kostouros, Stamatina Pagoni, Charis Matsouka, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2019)

383 Background: Venous thromboembolism (VTE) is a frequent complication of cancer or its treatment. Khorana (KRS) and Compass scores are two Risk Assessment Models for VTE. However, aUTC was not adequately represented and arterial events were not included, in these models. Methods: Data from pts with aUTC treated with at least one line of chemotherapy in our institution were analyzed. VaTE definition included: DVT and PE defined as venous events and peripheral arterial thrombosis or embolus, ischemic stroke and coronary events, grouped as arterial events. The association of baseline and treatment-related factors with the development of VaTE was assessed using competing-risk regressions. According to the results of our multivariate analysis we stratified patients according to the number of the identified risk factors. Results: 354 aUTC pts treated between 4/1995 and 9/2015 entered our study. 53% of pts had received cisplatin and 42% carboplatin-based regimens. 44 pts (12.4%) suffered 45 VaTEs (13 arterial, 32 venous) within a median time of 3.3 months. The cumulative and 6-month incidence was 14.8% (95% CI: 10.9-19.4) and 9.7% (95% CI: 6.8-13.1), [venous 10.5% (95% CI: 7.3-14.3)/7.5% (95% CI: 5-10.7); arterial 5.3% (95% CI: 2.8-9)/2.7% (95% CI: 1.3-5), respectively]. No association of the KRS and the COMPASS score with the incidence of VaTEs was observed. In the univariate and multivariate analysis, cumulative VaTE incidence was significantly increased in pts with “peripheral arterial disease (PAD) or history of VΤE” (adjusted SHR: 3.29; 95% CI: 1.65-6.55; p=0.001) and pts with other solid tumor (SHR: 2.20; 95% CI: 1.05-4.62; p=0.038). There was a strong correlation between the number of risk factors and the risk for VaTE development (p&lt;0.001). Patients with 1 or 2, vs 0 factors had a 3-fold increased risk [cumulative incidence was 10.9% (95% CI: 7.4.-15.2) and 30.2% (95% CI: 18.4-42.8), respectively; SHR: 3.01 95% CI: 1.65-5.51]. Conclusions: Development of tumor-specific algorithms for the risk of vascular events is supported by our results. Pts with aUTC and a history of VTE, PAD and other solid tumor have a very high risk for VaTE. The role of prophylaxis should be prospectively studied.
The Genome of Drosophila innubila Reveals Lineage-Specific Patterns of Selection in Immune Genes
Authors: Tom Hill, Boryana S Koseva, Robert L Unckless
Journal: Molecular Biology and Evolution (2019)

Pathogenic microbes can exert extraordinary evolutionary pressure on their hosts. They can spread rapidly and sicken or even kill their host to promote their own proliferation. Because of this strong selective pressure, immune genes are some of the fastest evolving genes across metazoans, as highlighted in mammals and insects. Drosophila melanogaster serves as a powerful model for studying host/pathogen evolution. While Drosophila melanogaster are frequently exposed to various pathogens, little is known about D. melanogaster's ecology, or if they are representative of other Drosophila species in terms of pathogen pressure. Here, we characterize the genome of Drosophila innubila, a mushroom-feeding species highly diverged from D. melanogaster and investigate the evolution of the immune system. We find substantial differences in the rates of evolution of immune pathways between D. innubila and D. melanogaster. Contrasting what was previously found for D. melanogaster, we find little evidence of rapid evolution of the antiviral RNAi genes and high rates of evolution in the Toll pathway. This suggests that, while immune genes tend to be rapidly evolving in most species, the specific genes that are fastest evolving may depend either on the pathogens faced by the host and/or divergence in the basic architecture of the host's immune system.
Abstract P365: Restless Leg Symptoms Predicts Adverse Cardiovascular Outcomes in Patients Undergoing Cardiac Catheterization
Authors: Jeong Hwan Kim, Syed Ali, Tiffany Dong, Ayman Samman Tahhan, Yi-An Ko, Salim Hayek, Ayman Alkhoder, Afif Martini, Mohamad M Gafeer, Arianna Sidoti, Ahsan Khan, Eesha A Zaheer, Martha Lemma, Fahad Choudhary, Muaaz Choudhary, Shahla Delawalla, Donald Bliwise, Arshed A Quyyumi
Journal: Circulation (2019)

Introduction: The association between restless leg syndrome (RLS) and CV outcomes remains controversial in the general population, and the impact of RLS among patients with coronary artery disease (CAD) is unknown. Hypothesis: We examined our hypothesis that RLS symptoms would be associated with incident adverse CV outcomes in patients with CAD. Methods: We inquired about the presence and frequency of RLS symptoms in 3,176 patients enrolled in the Emory Cardiovascular Biobank (mean age 64, 62% male, 23% Black, and 75% with obstructive CAD), who were prospectively followed for death, myocardial infarction (MI), revascularization, and hospitalization for heart failure (HF). Multivariate Cox proportional hazard models were used to examine the association between RLS symptoms and adverse outcomes after adjustment for demographic and clinical risk factors. Results: Of the total, 914 (28.8%) and 482 (15.2%) patients reported mild (rare or sometimes) and moderate/severe (often to almost always) symptoms of RLS, respectively. Female sex (Odds ratio [OR] 2.11, P&lt;0.001), higher body mass index (OR 1.12 per 5kg/m2, P=0.007), diabetes (OR 1.43, P=0.003), and beta blocker use (OR 1.35, P=0.013) were independently associated with moderate-severe symptoms of RLS compared to no symptoms. During a median 3.2-year follow-up, 991 patients suffered at least1 adverse event. Those with moderate/severe symptoms had significantly higher adjusted risk of death/MI (Hazard ratio [HR] 1.30 [1.02 - 1.66]), death/MI/revascularization (HR 1.22 [1.02 - 1.45]), and death/MI/revascularization/hospitalization for HF (HR 1.23 [1.04 - 1.45]). Those with mild symptoms had similar risks to those with no symptoms. Conclusions: Among patients undergoing cardiac catheterization, moderate or severe symptoms of RLS are associated with significantly higher risk of adverse CV outcomes, independent of traditional risk factors. This is the first study to demonstrate an independent adverse impact of RLS symptoms in CAD patients.
Black and white amid the colors of endoscopy – the march of endoscopic ultrasonography
Authors: Paul Fockens, Thomas Rösch
Journal: Endoscopy (2019)

In 1984, the 16th year of existence of the journal Endoscopy (now 50 years old), a first article was published on a previously unknown endoscopic technique called “endoscopic ultrasonography” [1]. Although the technique of endoscopy was still quite rudimentary, using instruments completely unlike the current ones, the Olympus Company from Tokyo, Japan had developed the first prototype series of echo-endoscopes, which they called GF-UM1, “GF” standing for “gastro-fiberoptic” and “UM” for “ultrasound mechanical.” The first small series of the GF-UM1 had been distributed to the leading endoscopy centers around the world in order to gain experience and insight into the potential of this new technique. Dr. Lok Tio was a gastroenterologist with considerable experience in abdominal ultrasonography, which was considered a prerequisite at that time. At the time of this publication he worked in the brand-new Academic Medical Center (AMC) in Amsterdam under the leadership of Professor Guido Tytgat, in a relatively small department with five gastroenterologists and four trainees. Dr. Tio had decided to devote his career to this novel technique and spent every day of the week in understanding and further developing the new modality. It is probably important to realize that in the early 1980 s, 35 years ago, the investigation of the gastrointestinal organs was also in its early phases. The main techniques were X-ray investigations with barium of the upper or lower gastrointestinal tract. Ultrasonography was available but lacked penetration and computed tomography had only recently been introduced. This was still a time when many laparotomies were performed every day as a purely diagnostic technique and all endoscopies were also mostly diagnostic, serving as guidance to surgical intervention.
<i>TES</i> functions as a Mena‐dependent tumor suppressor in gastric cancer carcinogenesis and metastasis
Authors: Dan‐dan Wang, Yi‐bing Chen, Jing‐jing Zhao, Xiao‐fei Zhang, Guang‐chao Zhu, De‐sheng Weng, Ke Pan, Lin Lv, Qiu‐zhong Pan, Shan‐shan Jiang, Lei‐lei Wang, Jian‐chuan Xia
Journal: Cancer Communications (2019)

In our previous study, we identified a candidate tumor suppressor gene, testin LIM domain protein (TES), in primary gastric cancer (GC). TES contains three LIM domains, which are specific interacting regions for the cell adhesion and cytoskeleton regulatory proteins. Mena is a known cytoskeleton regulator that regulates the assembly of actin filaments and modulates cell adhesion and motility by interacting with Lamellipodin (Lpd). Therefore, we hypothesized that TES plays a role as tumor suppressor in GC through interacting with Mena. This study aimed to investigate the tumor suppressive functions of TES in GC.We explored the tumor suppressive effect of TES in GC by in vitro cell proliferation assay, colony formation assay, cell cycle analysis, Transwell assays, and in vivo tumorigenicity and metastasis assays. The interaction of TES and Mena was investigated through immunoprecipitation-based mass spectrometry. We also analyzed the expression of TES and Mena in 172 GC specimens using immunohistochemistry and investigated the clinicopathological and prognostic significance of TES and Mena in GC.TES suppressed GC cell proliferation and colony formation, induced cell cycle arrest, and inhibited tumorigenicity in vitro. Additionally, it inhibited GC cell migration and invasion in vitro and suppressed metastasis in vivo. TES interacted with Mena, and inhibited the interaction of Mena with Lpd. Transwell assays suggested that TES suppressed migration and invasion of GC cells in a Mena-dependent fashion. In GC patients with high Mena expression, the expression of TES was associated with tumor infiltration (P = 0.005), lymph node metastasis (P = 0.003), TNM stage (P = 0.003), and prognosis (P = 0.010). However, no significant association was observed in GC patients with low Mena expression.We believe that TES functions as a Mena-dependent tumor suppressor. TES represents a valuable prognostic marker and potential target for GC treatment.
Duration of treatment (DOT) with targeted therapies (TT) or immunotherapy (IO) in PBRM1 mutated metastatic renal cell carcinoma (mRCC).
Authors: Nazli Dizman, Paulo Gustavo Bergerot, Cristiane Decat Bergerot, Joann Hsu, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2019)

622 Background: Current evidence indicates improved outcome with IO in mRCC patients (pts) with PBRM1 loss of function mutations (Miao et al., Nature, 2018). We seek to demonstrate an association between PBRM1 mutation and treatment duration with IO and TT in a retrospective cohort. Methods: Consecutive patients with mRCC who had genomic profiling in the course of routine clinical care were identified from an institutional database. GP assessments included testing either tissue or blood with 1 of the 3 CLIA certified commercial panels (Foundation Medicine, Cambridge, MA; Ashion Analytics, Phoenix, AZ; Guardant Health, Redwood City, CA). Information regarding systemic treatment was collected. Median DOT with first targeted therapy and first immunotherapy received was calculated for each patient. DOT was compared across treatment groups in PBRM1+ and PBRM1- patients. Only PBRM1 mutations with functional significance documented in COSMIC were considered. Results: Among 104 pts (72:32 M:F) with mRCC, 82 pts received TT, 35 pts received IO, and 45 pts received both. GP was performed in blood and tissue in 84 and 63 pts, respective, and 25 pts (24%) with PBRM1 mutations were identified. Among PBRM1+ pts, median DOT was 8.8 months (95% CI, 7.6-9.6) mos and 2.3 mos (95% CI, 1.7 – 2.8) mos with TT and IO, respectively (p=0.049). Among PBRM1- pts, median DOT was 5.5 mos and 2.8 mos with TT and IO, respectively (p=0.544). There were 11 PBRM1+ pts and 34 PBRM- pts who received both TT and IO. The ratio of DOT on IO to DOT on TT (DOT IO/TT ) was higher in PBRM1- pts than PBRM1+ pts (0.76 versus 0.37 respectively, p=0.014). Conclusions: We failed to replicate the results from Miao et al, suggesting clinical benefit with IO in PBRM1 mutated patients. PBRM1 mutation did appear to predict benefit with TT versus IO. Although limited by sample size, the contrasting results of the current study with literature highlight the importance of clinical validation in a large and prospective setting.
Abstract P409: Mortality in Subarachnoid Hemorrhage Varies by Day and Month Within the USA
Authors: David Rushworth, Amber Mathews, Adil Khan, Paul Litvak, Pitchaiah Mandava
Journal: Circulation (2019)

Introduction: High mortality is associated with aneurysmal subarachnoid hemorrhage (SAH). Despite years of studies and translational research, only a few health and lifestyle factors have been found to definitively associate with an increased risk of SAH incidence and mortality. Prior studies have provided some evidence that environmental factors play a role in the incidence of SAH, but the available data is not often consistent or applicable to the United States of America (USA). Here we provide support that there is a temporal differences in SAH mortality by month of the year and day of the week. Methods: The Centers for Disease Control (CDC) and Prevention public health database (wonder.cdc.gov) was accessed. Mortality events for the years 1999-2016 were obtained for deaths attributed to SAH from a named vessel distribution with accounting for day of week and month of year as well as gender from year to year. ANOVA was used to test for differences by week or month. Results: Mortality for week day variations found no significant differences (p = 0.13) in women, while men demonstrated a significant difference (p = 0.003) with the most common day of death being Monday. Mortality for monthly variation found a significant difference (p = 0.01) in total with January being the most common month of SAH mortality. However, divided by gender women (p = 0.06) and men (p = 0.10) did not meet predefined statistical significance. Conclusion: Mortality from SAH appears to have a variation in time of day of week in men and by month for both genders but this has unclear significance at this time.
Abstract 18978: CHA2DS2-VASc Score Predicts the Occurrence of Perioperative Stroke in CABG Patients Without Post-operative Atrial Fibrillation
Authors: Hugo Verdejo, Paula Barra, Ricardo Zalaquett, Isidro Huete, Ramon Corbalan
Journal: Circulation (2015)

Introduction: The CHA2DS2-VASc score is a clinical guideline for assessing ischemic stroke risk in patients with atrial fibrillation (AF). However, new evidence suggest that the CHA2DS2-VASc predicts vascular dysfunction and cardiovascular events in high-risk CV patients without clinical AF. Hypothesis: The CHA2DS2-VASc score predicts the occurrence of perioperative stroke in patients in sinus rhythm submitted to CABG in absence of post-operative AF Methods: We analyzed 112 consecutive patients in sinus rhythm and without history of AF who were submitted to elective CABG. Clinical and laboratory characteristics were recorded at baseline and 72 h after surgery. All subjects were monitored for 72 hours to exclude postoperative AF. A standardized MRI with stroke protocol was performed in the preoperative period in all subjects and within 5 days after surgery to detect evidence of perioperative stroke. Results: Patient mean age was 65 ± 15 years, 81.2% male. During follow-up, 26.8% of the patients showed new defects in MRI compatible with ischemic stroke, but only two exhibited overt neurological impairment. Baseline and postoperative inflammatory and coagulation markers, CPB and aortic clamp time as well as standard echocardiographic characteristics were similar in patients with and without perioperative stroke. CHA2DS2-VASc score was higher in patients who developed perioperative stroke (3.13 ± 1.4 vs 2.30 ± 1.2, p=0.01). Figure 1 shows the distribution of stroke cases according to CHA2DS2-VASc score. In a multivariate analysis, CHA2DS2-VASc2 was the only independent predictor of perioperative stroke in this population (HR 1.55, 95% CI 1.104-2.176, p=0.01). Conclusions: The CHA2DS2-VASc score predicts the occurrence of perioperative stroke in CABG patients without clinical AF. Patients with a score of 3 or more exhibit an increased risk for perioperative stroke even after adjusting for age, smoking and significant comorbidities. FONDECYT 1100801