tbuckley/cabot-search huggingface dataset:
Abstract B71: Stochastic model of contact inhibition and the proliferation of melanoma in situ
Authors: Mauro Cesar C. Morais, Izabella Stuhl, Alan U. Sabino, Willian W. Lautenschlager, Alexandre S. Queiroga, Tharcisio C. Tortelli, Roger Chammas, Yuri Suhov, Alexandre F. Ramos
Journal: Clinical Cancer Research (2018)

Abstract Contact inhibition of proliferation can be described as the decrease of proliferation rates when the cell density increases. Its loss is a key feature of tumor development. Cell density of human metastatic melanoma cell line (SK-MEL-147) and immortalized keratinocyte cells (HaCaT) was evaluated daily in culture experiments. Keratinocytes reach lower cell density than melanoma cells at confluence, indicating that the population growth arrest is associated with contact inhibition (KHaCaT = 1779.6 ± 130.5 cells/mm2; KSK-MEL-147 = 5043.5 ± 316.5 cells/mm2). We performed a coculture experiment to assess the proliferation restriction between both cell lines. After 8 days a spatial pattern was detected, characterized by the formation of clusters of melanoma cells surrounded by keratinocytes constraining their proliferation. Despite showing approximately the same proliferation rates when data were fitted with a logistic model (ρHaCaT = 1.1 ± 0.1 days-1; ρSK-MEL-147 = 1.1 ± 0.3 days-1), the proportion of melanoma cells within the total population has increased from 1:10 to 1:4 approximately. To explain our results we propose a spatial stochastic model where we consider cell proliferation, death, migration, and cell-to-cell interaction through contact inhibition. The agreement between experimental results and numerical simulation indicates that loss of contact inhibition is important for the analysis of the development of melanoma in situ, and explains the increase in the proportion of tumor cells and generation of spatial patterns established in conducted experiments. In addition, the distribution of the distances between cells of the same line indicates the higher proximity of melanoma cells and allowed us to identify their clustering pattern. This work provides results of a quantitative study of the impact of contact inhibition upon formation and growth of tumor-like melanoma cell clusters in a coculture with keratinocytes. Citation Format: Mauro Cesar C. Morais, Izabella Stuhl, Alan U. Sabino, Willian W. Lautenschlager, Alexandre S. Queiroga, Tharcisio C. Tortelli, Jr., Roger Chammas, Yuri Suhov, Alexandre F. Ramos. Stochastic model of contact inhibition and the proliferation of melanoma in situ [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B71.
Respiratory allergies with no associated food allergy disrupt oral mucosa integrity
Authors: Javier Sanchez‐Solares, Maria I. Delgado‐Dolset, Leticia Mera‐Berriatua, Gonzalo Hormias‐Martin, Jose A. Cumplido, Vanesa Saiz, Teresa Carrillo, Carmen Moreno‐Aguilar, Maria M. Escribese, Cristina Gomez‐Casado, Domingo Barber
Journal: Allergy (2019)

The authors declare that they have no conflicts of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract P6-17-30: Changes in patient, tumor, and treatment characteristics over time in first-line trastuzumab plus taxane (paclitaxel/docetaxel) arms in HER2-positive metastatic breast cancer trials
Authors: T Badovinac Crnjevic, E Restuccia, F Michielin, J Eng-Wong, E Nüesch
Journal: Cancer Research (2019)

Abstract Background: A retrospective analysis showed improved progression-free survival and consistent underestimation of trastuzumab (H) + taxane (T) efficacy assumptions in first-line (1L) human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) trials over time (ISCB 2016). We evaluated changes in baseline and treatment characteristics and the safety profile of H+T in 1L HER2-positive MBC trials conducted during 1995–2015. Methods: Trial-level data on patient, tumor, and treatment characteristics and safety profiles in H+T arms of 15 randomized trials were extracted from published data and clinical study reports. Characteristic and safety profile changes over time were explored by weighted regression; relevance was assessed by F-test. Results: Patient and tumor characteristics were generally stable over time. We observed relevant changes in types of adjuvant therapy used. Serious adverse events (SAEs) and study withdrawals due to Aes decreased over time; rates of treatment discontinuation due to Aes increased. No. of trials (patients)Difference in patients with characteristic per 5 years, % (95% CI)P valueBaseline characteristics Median age15 (2895)0.5 (0.1, 0.9)*.28ECOG status 012 (2472)0.2 (-1.1, 1.6).87Hormone receptor-positive11 (2124)1.3 (-1.1, 3.6).61HER2 IHC 3+8 (1657)5.8 (3.0, 8.6).08Visceral disease10 (1970)0.5 (-2.5, 3.6).86Adjuvant therapy Hormonal therapy11 (2194)-10.1 (-12.4, -7.8).002Radiotherapy9 (2010)-4.2 -5.8, -2.6).035HER2-targeted therapy9 (2176)20.2 (13.0, 27.4).026Chemotherapy15 (2893)-7.0 (-9.2, -4.7).008Safety Grade 3+ AE6 (1342)-15.4 (-28.4, -2.5).30SAE7 (1462)-12.6 (-15.4, -9.8).006Study withdrawal due to AE8 (1525)-6.8 (-9.0, -4.5).023Treatment discontinuation due to AE6 (1370)11.5 (6.7, 16.3).075*Years (95% CI). AE, adverse events; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; IHC, immunohistochemistry; SAE, serious adverse events. Conclusions: In 1L HER2-positive MBC trials, the percentage of patients who received adjuvant chemo-, hormonal, and radio-therapy decreased from 1995 to 2015. These changes in treatment patterns suggest a shift towards a higher percentage of patients with de novo metastatic vs recurrent disease in 1L MBC trials over time. Adjuvant H use increased following approval in 2005 as expected. While SAEs decreased over time, no firm conclusions on safety management can be made. Citation Format: Badovinac Crnjevic T, Restuccia E, Michielin F, Eng-Wong J, Nüesch E. Changes in patient, tumor, and treatment characteristics over time in first-line trastuzumab plus taxane (paclitaxel/docetaxel) arms in HER2-positive metastatic breast cancer trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-30.
Abstract 19292: Cardiovascular Secondary Prevention Therapies are Underprescribed in Patients With Peripheral Artery Disease: Findings From the NCDR PINNACLE Registry
Authors: David W Lee, Prashant Kaul, George A Stouffer, Sidney C Smith, Anvar Babaev, Thomas M Maddox, Stacie L Daugherty, Salim S Virani, Mazen Albaghdadi, Christopher P Cannon, Gheorghe Doros, Yuyin Liu, Matthew A Cavender
Journal: Circulation (2017)

Introduction: Peripheral artery disease (PAD) guidelines recommend anti-platelet, lipid-lowering, anti-hypertensive, diabetic, and smoking cessation therapies to prevent cardiovascular events. We d...
Comparative Analysis for Effectiveness of Azacitidine Versus Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes with Marrow Fibrosis: A Single Institution Experience
Authors: Ala Ebaid, Shashank Y. Cingam, Tawny Boyce, Daniel Babu, Qiuying Selina Liu, Khine Win, Cecilia Y. Arana Yi
Journal: Blood (2019)
Abstract P2-14-15: Breast cancer-related lymphedema: Morbidity of sentinel node biopsy
Authors: YW Ju, JG Jung, KE Kim, Y Kim, E Lee, H-B Lee, H-G Moon, W Han, D-Y Noh
Journal: Cancer Research (2019)

Abstract Purpose: Sentinel lymph node biopsy (SLNB) lowers morbidity of lymphedema then axillary lymph node dissection (ALND). However, there has been concern about incidence of lymphedema after SLNB especially when the number of harvested nodes during sentinel node biopsy procedure is more than a few. In this study, we assessed lymphedema incidence and its risk factors including the number excised lymph nodes in patients who underwent SLNB. Methods: Between January, 2011 and April, 2012, the records of 910 consecutive patients who underwent breast surgery with axillary staging (SLNB/ALND) for breast cancer at Seoul National University Hospital were reviewed. Lymphedema was assessed by circumferential upper extremity measurements. The lymphedema was defined as &amp;gt; 1cm for either the upper arm or the forearm. Patients with clinical records of the treatment for lymphedema in the rehabilitation clinic were regarded as having lymphedema. Univariate and multivariate analyses were performed to identify potential risk factors associated with lymphedema. Association of number of excised lymph nodes with lymphedema was analyzed by Spearman rank correlation coefficient. Results: At median follow-up of 69.8 months, 231 patients (25.4%) presented with lymphedema. In univariate analysis, body mass index (BMI) (P&amp;lt;0.001), T stage (P&amp;lt;0.001), N stage (P&amp;lt;0.001), type of surgery (P&amp;lt;0.001), ALND (P&amp;lt;0.001), neoadjuvant chemotherapy (P&amp;lt;0.001) and adjuvant chemotherapy (P=0.027) were significantly associated with lymphedema. In multivariate analysis BMI (P&amp;lt;0.001), ALND (P&amp;lt;0.001), neoadjuvant chemotherapy (P=0.044), and radiation therapy (P=0.046) were significantly associated with lymphedema. In patients treated with SLNB only (n=595), the incidence of lymphedema was 16.3% (n=97). In SLNB only subgroup, BMI was only significant risk factor of lymphedema. There was no correlation between number of excised lymph nodes during sentinel lymph node biopsy procedure with incidence of lymphedema (P=0.138). Conclusion: The risk of lymphedema is multifactorial in breast cancer surgery and adjuvant treatments. In SLNB alone patients, higher BMI was only significant factor correlated with lymphedema. Excised number of lymph nodes during sentinel biopsy procedure was not associated with lymphedema. Citation Format: Ju YW, Jung JG, Kim KE, Kim Y, Lee E, Lee H-B, Moon H-G, Han W, Noh D-Y. Breast cancer-related lymphedema: Morbidity of sentinel node biopsy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-15.
Hyponatraemia in primary care
Authors: Peter Jacob, Claire Dow, Shawarna S. Lasker, William M. Drake, Tahseen A. Chowdhury
Journal: BMJ (2019)

### What you need to know

Hyponatraemia is the most frequently observed electrolyte abnormality.1 Mild hyponatraemia is associated with cognitive deficits and falls, but in hospitalised patients it is associated with increased mortality.2 In primary care, patients are often found to have hyponatraemia during chronic disease monitoring. This prompts a focused re-evaluation to consider underlying causes such as medication, cancer, or adrenal insufficiency.23 In this article we provide a framework to assess patients with hyponatraemia in primary care.

Hyponatraemia is defined as a serum sodium value below the reference range (lower limit is usually 133-135 mmol/L). Hyponatraemia is often subdivided into mild, moderate, severe, and life threatening, using a combination of the presence of associated symptoms and the sodium value.34 There is, however, a poor correlation between symptomatology and serum sodium level, so both must be taken into account when considering urgency of referral and subsequent management. Hyponatraemia may be acute (arbitrarily defined as an onset within 48 hours), chronic (>48 hours), or unknown (where management should be as per chronic). 

Although it may appear to be asymptomatic, even at modest levels hyponatraemia may predispose to falls and cognitive deficits. In a case-control study of 122 patients with hyponatraemia and 244 matched controls, 21% of patients had been admitted with falls compared with 5% of controls.5 The risk of falls was elevated with any sodium value below 132 mmol/L. Chronic hyponatraemia is a risk factor …
Solid stress, competition for space and cancer: The opposing roles of mechanical cell competition in tumour initiation and growth
Authors: Romain Levayer
Journal: Seminars in Cancer Biology (2019)

The regulation of cell growth, cell proliferation and cell death is at the basis of the homeostasis of tissues. While they can be regulated by intrinsic and genetic factors, their response to external signals emanating from the local environment is also essential for tissue homeostasis. Tumour initiation and progression is based on the misregulation of growth, proliferation and death mostly through the accumulation of genetic mutations. Yet, there is an increasing body of evidences showing that tumour microenvironment also has a strong impact on cancer initiation and progression. This includes the mechanical constrains and the compressive forces generated by the resistance of the surrounding tissue/matrix to tumour expansion. Recently, mechanical stress has been proposed to promote competitive interactions between cells through a process called mechanical cell competition. Cell population with a high proliferative rate can compact and eliminate the neighbouring cells which are more sensitive to compaction. While this emerging concept has been recently validated in vivo, the relevance of this process during tumour progression has never been discussed extensively. In this review, I will first describe the phenomenology of mechanical cell competition focusing on the main parameters and the pathways regulating cell elimination. I will then discuss the relevance of mechanical cell competition in tumour initiation and expansion while emphasizing its potential opposing contributions to tumourogenesis.
Efficacy and Safety of Fast-Acting Insulin Aspart Compared With Insulin Aspart, Both in Combination With Insulin Degludec, in Children and Adolescents With Type 1 Diabetes: The onset 7 Trial
Authors: Bruce W. Bode, Violeta Iotova, Margarita Kovarenko, Lori M. Laffel, Paturi V. Rao, Srikanth Deenadayalan, Magnus Ekelund, Steffen Falgreen Larsen, Thomas Danne
Journal: Diabetes Care (2019)

To confirm efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp), both with basal insulin degludec, in a pediatric population with type 1 diabetes.After a 12-week run-in, this treat-to-target, 26-week, multicenter trial randomized participants (1 to <18 years) to double-blind mealtime faster aspart (n = 260), mealtime IAsp (n = 258), or open-label postmeal faster aspart (n = 259). The primary end point was change from baseline in glycated hemoglobin (HbA1c) after 26 weeks of treatment. All available information regardless of treatment discontinuation was used for the evaluation of treatment effect.At week 26, mealtime and postmeal faster aspart were noninferior to IAsp regarding change from baseline in HbA1c (P < 0.001 for noninferiority [0.4% margin]), with a statistically significant difference in favor of mealtime faster aspart (estimated treatment difference -0.17% [95% CI -0.30; -0.03], -1.82 mmol/mol [-3.28; -0.36]; P = 0.014). Change from baseline in 1-h postprandial glucose increment significantly favored mealtime faster aspart versus IAsp at breakfast, main evening meal, and over all meals (P < 0.01 for all). No statistically significant differences in the overall rate of severe or blood glucose-confirmed hypoglycemia were observed. Mean total daily insulin dose was 0.92 units/kg for mealtime faster aspart, 0.92 units/kg for postmeal faster aspart, and 0.88 units/kg for mealtime IAsp.In children and adolescents with type 1 diabetes, mealtime and postmeal faster aspart with insulin degludec provided effective glycemic control with no additional safety risks versus IAsp. Mealtime faster aspart provided superior HbA1c control compared with IAsp.
Transverse stent placement for hilar malignant biliary obstruction through an endoscopic ultrasound-guided hepaticogastrostomy route
Authors: Sachiko Kanai, Tomotaka Saito, Ryunosuke Hakuta, Yousuke Nakai, Kazuhiko Koike
Journal: Endoscopy (2019)

A 70-year-old woman who had undergone endoscopic placement of multiple stents for hilar biliary obstruction due to gallbladder cancer was admitted with cholangitis. In her previous hospitalization, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) had been performed for the bile duct at segment III (B3) using a partially covered self-expandable metal stent (SEMS; modified Giobor, 10 × 80 mm; Taewoong Medical Inc., Gimpo, Korea [1]). To manage subsequent episodes of cholangitis, two uncovered SEMSs were placed via the transpapillary route for B7 and B8 in a partial stent-in-stent fashion ([Fig. 1]). On this admission, endoscopic drainage was scheduled to manage segmental cholangitis in B8.
Abstract P2-08-55: Not presented
Authors: H Zhang, T-H Liu, L-Q Zhang, J Li, J Cui, X-Y Tian, D-N Li, J-P Cai
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Zhang H, Liu T-H, Zhang L-Q, Li J, Cui J, Tian X-Y, Li D-N, Cai J-P. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-55.
Health Effects of Household Solid Fuel Use: Findings from 11 Countries within the Prospective Urban and Rural Epidemiology Study
Authors: Perry Hystad, MyLinh Duong, Michael Brauer, Andrew Larkin, Raphael Arku, Om P. Kurmi, Wen Qi Fan, Alvaro Avezum, Igbal Azam, Jephat Chifamba, Antonio Dans, Johan L. du Plessis, Rajeev Gupta, Rajesh Kumar, Fernando Lanas, Zhiguang Liu, Yin Lu, Patricio Lopez-Jaramillo, Prem Mony, Viswanathan Mohan, Deepa Mohan, Sanjeev Nair, Thandi Puoane, Omar Rahman, Ah Tse Lap, Yanga Wang, Li Wei, Karen Yeates, Sumathy Rangarajan, Koon Teo, Salim Yusuf
Journal: Environmental Health Perspectives (2019)

Background: Household air pollution (HAP) from solid fuel use for cooking affects 2.5 billion individuals globally and may contribute substantially to disease burden. However, few prospective studies have assessed the impact of HAP on mortality and cardiorespiratory disease. Objectives: Our goal was to evaluate associations between HAP and mortality, cardiovascular disease (CVD), and respiratory disease in the prospective urban and rural epidemiology (PURE) study. Methods: We studied 91,350 adults 35–70 y of age from 467 urban and rural communities in 11 countries (Bangladesh, Brazil, Chile, China, Colombia, India, Pakistan, Philippines, South Africa, Tanzania, and Zimbabwe). After a median follow-up period of 9.1 y, we recorded 6,595 deaths, 5,472 incident cases of CVD (CVD death or nonfatal myocardial infarction, stroke, or heart failure), and 2,436 incident cases of respiratory disease (respiratory death or nonfatal chronic obstructive pulmonary disease, pulmonary tuberculosis, pneumonia, or lung cancer). We used Cox proportional hazards models adjusted for individual, household, and community-level characteristics to compare events for individuals living in households that used solid fuels for cooking to those using electricity or gas. Results: We found that 41.8% of participants lived in households using solid fuels as their primary cooking fuel. Compared with electricity or gas, solid fuel use was associated with fully adjusted hazard ratios of 1.12 (95% CI: 1.04, 1.21) for all-cause mortality, 1.08 (95% CI: 0.99, 1.17) for fatal or nonfatal CVD, 1.14 (95% CI: 1.00, 1.30) for fatal or nonfatal respiratory disease, and 1.12 (95% CI: 1.06, 1.19) for mortality from any cause or the first incidence of a nonfatal cardiorespiratory outcome. Associations persisted in extensive sensitivity analyses, but small differences were observed across study regions and across individual and household characteristics. Discussion: Use of solid fuels for cooking is a risk factor for mortality and cardiorespiratory disease. Continued efforts to replace solid fuels with cleaner alternatives are needed to reduce premature mortality and morbidity in developing countries. https://doi.org/10.1289/EHP3915
Pushing at the open door
Authors: Adal Mirza
Journal: BMJ (2010)

“I might as well have stayed in bed, they don’t even know we’re here,” despaired the young medical student.

Many students languish invisible to the ever busy doctors as they hasten about their days. As a recently qualified doctor, I can sympathise with this frustration. That said, there are two sides to every story and this story is no exception.

The General Medical Council reminds us that, “Teaching, training, appraising and assessing students …
Abstract 2434: LEF1 negatively regulates differentiation of HCC by activation of Notch signaling pathway
Authors: Shuo FANG, Lei LI, MIng LIU, Janice Tsang, Xinyuan GUAN
Journal: Cancer Research (2017)

Abstract Lymphoid enhancer binding factor-1 (LEF1), an essential regulatory protein, plays a crucial role on self-renewal and differentiation properties of several cancers, contributing to tumor malignancy degree and prognosis. However, its molecular mechanisms to promote tumor differentiation still keep unknown, especially in hepatocellular carcinoma (HCC). In this study, by analyzing the transcriptome datasets and our qPCR result of clinical HCC samples, we found that LEF is frequently overexpressed in HCCs and significantly associated with HCC differentiation (p=0.015). In addition, functional study showed that LEF1 could enhance the cell proliferation, matrigel invasion, transwell migration, as well as self-renewal abilities both in vivo and in vitro experiments. We also demonstrated LEF1 is closely related to Notch intracellular domain (NICD), and revealed several putative sites as the targets for LEF1 activating Notch signaling pathway. LEF1 could induce the Notch signaling via transcriptionally up-regulate Notch expression through direct DNA binding. The expressions of several downstream members in Notch signaling pathway including Notch1 and Notch2 were subsequently increased. Moreover, LEF1 could down-regulate various differentiation markers and over-express tumor stemness related genes. Together, LEF1 is a novel oncogene that show a crucial role in the tumorigenesis and progression of HCC via activating Notch signaling pathway and inhibiting the differentiation and stemness of HCC, resulting in poor pathologic differentiation and leads to high degree of malignant. All the findings suggest a novel treatment possibility and a new target for liver stem cell eradication. LEF1 could be investigated for clinical early diagnosis and prognosis prediction of HCC patients and improving the development of new therapy against HCC. Note: This abstract was not presented at the meeting. Citation Format: Shuo FANG, Lei LI, MIng LIU, Janice Tsang, Xinyuan GUAN. LEF1 negatively regulates differentiation of HCC by activation of Notch signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2434. doi:10.1158/1538-7445.AM2017-2434
Reply: Limitations in the creation of an automatic diagnosis tool for dysgraphia
Authors: Thibault Asselborn, Thomas Gargot, Łukasz Kidziński, Wafa Johal, David Cohen, Caroline Jolly, Pierre Dillenbourg
Journal: npj Digital Medicine (2019)

KinematicIn Air Time Ratio 0.91 (0.86)We report the ranks, features categories and their importance averaged for the 25 folds and the standard deviation of importance over all folds
A self-confessed whiner
Authors: Sarah Welsh
Journal: BMJ (2011)

In Stitches , the true story of an accident and emergency doctor, was a success in the UK. This revised and updated edition includes new stories of disturbing, moving, and memorable moments behind the doors of an emergency department.

Nick Edwards writes of “the highs and lows of being an A&E doctor.” His collection of blog-like extracts deal with current events and his experiences …