Locally advanced gastroesophageal junction tumor: a treatment dilemma.

Over the last several decades, the incidence of adenocarcinoma of the gastroesophageal junction (GEJ) has been increasing in developed countries. Although complete surgical resection remains the cornerstone of treatment for resectable disease, long-term outcomes are poor and recurrence rates are high with surgery alone in patients presenting with locally advanced disease. Multimodal therapy has been shown to improve survival; however, the optimal therapeutic approach remains controversial, and practices vary across the world. Preoperative chemoradiotherapy is generally used in the U.S., whereas perioperative chemotherapy without radiation is favored in most European countries. In this review, we discuss why the treatment of locally advanced GEJ tumors remains controversial, examine the evidence for various multimodal approaches, discuss their respective pros and cons, evaluate the role of radiation therapy, highlight some ongoing and planned clinical trials, and suggest areas that need further research.

Predictive biomarkers for anti-epidermal growth factor receptor therapy: beyond KRAS testing.

In an era of personalized medicine, an increased effort is being made to identify patients likely to benefit from targeted therapy. By limiting treatment to selected patients, both unnecessary cost and toxicity may be avoided. Restricting the use of anti-epidermal growth factor receptor (anti-EGFR)-targeted agents in metastatic colorectal cancer to only patients with KRAS exon 2 wild-type tumors has become well-established in clinical practice. However, lack of KRAS exon 2 mutations does not necessarily predict response, and a significant proportion of patients with KRAS wild-type tumors do not benefit from therapy with cetuximab or panitumumab. Further characterization is needed of the subset of patients with KRAS exon 2 wild-type tumors who are likely to benefit from anti-EGFR therapy. Recent data suggest that patients with KRAS mutations at loci other than exon 2, and those with other RAS mutations, might not benefit from EGFR-directed therapy. This article briefly reviews established work on KRAS exon 2 mutations, but focuses primarily on emerging data on non-exon 2 KRAS mutations and additional RAS and BRAF mutations and how this information may impact clinical decision-making.

A Qualitative Study Exploring Barriers to Colorectal Cancer Screening Among Firefighters.

OBJECTIVE: Firefighters are at increased risk of colorectal cancer (CRC), yet rates of CRC screening are low among this occupational group. This study examines perceived risks, barriers, and facilitators to CRC screening. METHODS: Three semistructured focus group discussions were conducted by investigators in Tucson, AZ. Thematic analysis was used to identify patterns and themes in the data. RESULTS: Three groups of firefighters (8 male (57%); 6 female (43%) mean age 50.4 ( SD = 12.2) years) voluntarily participated in the CRC discussions. Four major themes were examined: (1) perceptions of risk for CRC, (2) barriers to cancer screening, (3) facilitators to getting cancer screening, and (4) misinformation about CRC and screening. CONCLUSIONS: Findings indicate unique perceptions, attitudes, and beliefs among firefighters. Results from this study will inform the adaptation of a tailored CRC screening intervention for firefighters.

Adjuvant treatment for gastric cancer: chemotherapy versus radiation.

Gastric cancer is among the leading causes of cancer death worldwide. Surgery is the only curative modality, but mortality remains high because a significant number of patients have recurrence after complete surgical resection. Chemotherapy, radiation, and chemoradiotherapy have all been studied in an attempt to reduce the risk for relapse and improve survival. There is no globally accepted standard of care for resectable gastric cancer, and treatment strategies vary across the world. Postoperative chemoradiation with 5-fluorouracil/leucovorin is most commonly practiced in the United States; however, recent clinical trials from Asia have shown benefit of adjuvant chemotherapy alone and have questioned the role of radiation. In this review, we examine the current literature on adjuvant treatment of gastric cancer and discuss the roles of radiation and chemotherapy, particularly in light of these new data and their applicability to the Western population. We highlight some of the ongoing and planned clinical trials in resectable gastric cancer and identify future directions as well as areas where further research is needed.

Identification of phytochemicals as putative ligands for the targeted modulation of peroxisome proliferator-activated receptor α (PPARα) in animals.

The PPAR family of transcription factors are ligand-activated and regulate diverse functions including metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction in the body. Specifically, PPARα is known to play a role in reducing the levels of circulating triglycerides and regulating energy homeostasis in livestock animals. This study aimed to identify phytochemicals that could serve as ligands for modulation of the bovine nuclear peroxisome proliferator-activated receptor alpha (PPARα) using molecular docking studies. Therefore, we investigated 1000 flavonoids belonging to different groups for their ability to bind to PPARα using molecular docking. Out of 1000, 6 top lead compounds with maximum binding affinity, evaluated through molecular docking, were further analysed for physicochemical properties and drug-likeness attributes. The results revealed that two flavonoids, Quercetin-3-o-rhamnoside and (-)- epicatechingallate, which are known fatty acid synthase inhibitors, demonstrated high docking scores with PPARα (-8.66 kcal/mol and -8.49 kcal/mol, respectively) and low RMSD values with PPARα (1.61 kcal/mol and 1.28 kcal/mol, respectively) as compared to PPARα agonist (synthetic), fenofibrate (-6.24 kcal/mol and 2.19 kcal/mol) and thus analyzed further for prediction of stability of docked complexes through MD simulations. MD simulation studies predicted the stability of complexes and the complex of Quercetin-3-o-rhamnoside and (-)- epicatechingallate were found to be stable at 100 ns based on RSMD value and RMSF residue index. Through computational analysis, the screened compounds showed good pharmacokinetic parameters, including non-toxicity, non-carcinogenic, high gastrointestinal absorption and thus can serve as potential drug candidates. Finally, the findings suggest that these phytochemicals have the potential to act as potent PPARα pharmacological agonists to prevent disease mechanisms and their related complications, providing insights into the role of phytochemicals as feed additives in animals for modulating PPARα functions.Communicated by Ramaswamy H. Sarma.

Multi-class sentiment analysis of urdu text using multilingual BERT.

Sentiment analysis (SA) is an important task because of its vital role in analyzing people's opinions. However, existing research is solely based on the English language with limited work on low-resource languages. This study introduced a new multi-class Urdu dataset based on user reviews for sentiment analysis. This dataset is gathered from various domains such as food and beverages, movies and plays, software and apps, politics, and sports. Our proposed dataset contains 9312 reviews manually annotated by human experts into three classes: positive, negative and neutral. The main goal of this research study is to create a manually annotated dataset for Urdu sentiment analysis and to set baseline results using rule-based, machine learning (SVM, NB, Adabbost, MLP, LR and RF) and deep learning (CNN-1D, LSTM, Bi-LSTM, GRU and Bi-GRU) techniques. Additionally, we fine-tuned Multilingual BERT(mBERT) for Urdu sentiment analysis. We used four text representations: word n-grams, char n-grams,pre-trained fastText and BERT word embeddings to train our classifiers. We trained these models on two different datasets for evaluation purposes. Finding shows that the proposed mBERT model with BERT pre-trained word embeddings outperformed deep learning, machine learning and rule-based classifiers and achieved an F1 score of 81.49%.

Multi-label emotion classification of Urdu tweets.

Urdu is a widely used language in South Asia and worldwide. While there are similar datasets available in English, we created the first multi-label emotion dataset consisting of 6,043 tweets and six basic emotions in the Urdu Nastalíq script. A multi-label (ML) classification approach was adopted to detect emotions from Urdu. The morphological and syntactic structure of Urdu makes it a challenging problem for multi-label emotion detection. In this paper, we build a set of baseline classifiers such as machine learning algorithms (Random forest (RF), Decision tree (J48), Sequential minimal optimization (SMO), AdaBoostM1, and Bagging), deep-learning algorithms (Convolutional Neural Networks (1D-CNN), Long short-term memory (LSTM), and LSTM with CNN features) and transformer-based baseline (BERT). We used a combination of text representations: stylometric-based features, pre-trained word embedding, word-based n-grams, and character-based n-grams. The paper highlights the annotation guidelines, dataset characteristics and insights into different methodologies used for Urdu based emotion classification. We present our best results using micro-averaged F1, macro-averaged F1, accuracy, Hamming loss (HL) and exact match (EM) for all tested methods.

Impact of Location and Insulation Material on Energy Performance of Residential Buildings as per Saudi Building Code (SBC) 601/602 in Saudi Arabia.

In hot and humid climates, a significant part of the energy is used to cool the building. There are several ways to reduce this air conditioning load, but one standout is through the selection and design of the right building envelope and its components. The thermal characteristics of the building envelope, in particular the thermal resistance of the insulation used, have an impact on the thermal and energy performance of building structures. Thermal conductivity, which indicates the ability of heat to move through a material given a temperature difference, is the primary factor affecting the performance of a thermal insulation material. Both temperature and humidity changes can affect a material's thermal conductivity value, which can then change. In fact, due to the fluctuating ambient air temperature and solar radiation, thermal insulation in buildings is susceptible to significant and continuous temperature variations. Thermal insulation used in building walls and roofs helps to reduce the energy demand of the building. It improves thermal comfort and, if used correctly, reduces the operational cost of the building. The present study has focused on the effects of location and insulation material on the energy performance of a residential building by considering five climatic locations in the Kingdom of Saudi Arabia (KSA). Five commonly used insulation materials with different thermal characteristics, namely polyurethane board (PU), expanded polystyrene (EPS), glass wool (GW), urea-formaldehyde foam (UFF), and expanded perlite (EP), were analyzed under various climatic zones as per the Saudi Building Code 601/602. The selected cities were categorized based on cooling degree days (CDD) and outdoor dry bulb temperature (DBT) as hot, very hot, and extremely hot climatic zones. Insulation improves thermal comfort and, if used correctly, reduces running costs. Experiments were conducted to determine the thermal conductivity, and the energy simulation was performed by employing IES-VE software for various insulation options. The findings indicate that the location has a significant impact on the energy performance of the insulating materials. The energy saving potential of polyurethane board (PU) insulation is more attractive in cities with higher DBTs and CDDs than in cities with lower DBTs and CDDs. The benefit of installing insulation ranged from a 2 to 14% decrease in energy demand for the climate zones studied. The sensitivity analysis showed that the energy saving potential of the insulation materials is sensitive to the set-point temperature (ST) band.

Abusive language detection in youtube comments leveraging replies as conversational context.

Nowadays, social media experience an increase in hostility, which leads to many people suffering from online abusive behavior and harassment. We introduce a new publicly available annotated dataset for abusive language detection in short texts. The dataset includes comments from YouTube, along with contextual information: replies, video, video title, and the original description. The comments in the dataset are labeled as abusive or not and are classified by topic: politics, religion, and other. In particular, we discuss our refined annotation guidelines for such classification. We report a number of strong baselines on this dataset for the tasks of abusive language detection and topic classification, using a number of classifiers and text representations. We show that taking into account the conversational context, namely, replies, greatly improves the classification results as compared with using only linguistic features of the comments. We also study how the classification accuracy depends on the topic of the comment.

A Novel Case of Leflunomide-Induced Thrombotic Thrombocytopenic Purpura.

Leflunomide has not been previously associated with thrombotic thrombocytopenic purpura (TTP), a rare life-threatening clinical syndrome characterized by thrombotic microangiopathy (TMA) due to inability to cleave ADAMTS13. Here, we present the first case of leflunomide-induced TTP. Our patient developed encephalopathy, thrombocytopenia, anemia and hyperbilirubinemia 2 months after starting leflunomide. Schistocytes were noted on peripheral smear and ADAMTS13 activity was low (< 5%), consistent with acquired TTP. He received therapeutic plasma exchange, corticosteroids, rituximab and caplacizumab with normalization of hemolysis labs and ADAMTS13 activity. However, pancytopenia persisted, raising the suspicion for leflunomide toxicity. Oral cholestyramine treatment was empirically started before teriflunomide (a leflunomide metabolite) level was found to be elevated. Blood counts normalized after cholestyramine and have remained normal at last follow-up over a year later. This is the first reported case of TTP precipitated by leflunomide. Our case highlights the importance of recognizing drugs as an etiology of TMA and adds leflunomide to this list.

Evolving paradigm in thrombophilia screening.

: The role of genetic thrombophilia screening for identifying a hypercoagulable state in the management of venous thromboembolism. We searched MEDLINE and EMBASE from 1995 to 2017, the websites of the professional bodies including American Society of Hematology, British Society of Hematology, International Society of Thrombosis and Hemostasis, College of American Pathologists, American College of Medical Genetics, and American Society of obstetrics and gynecology for their clinical practice guidelines. We used search strategy terms - venous thromboembolism, inherited, thrombophilia, and hypercoagulable state. Thrombophilia screening does not alter management in pregnancy, infertility, recurrent miscarriages, in primary occlusive arterial syndromes, and for primary prevention in relatives of venous thromboembolism patients considering hormonal manipulation including oral contraceptives. Routine thrombophilia screening for identifying a hypercoagulable state is not indicated in venous thromboembolism, as it is only useful in a select group of patients. There is no difference in the treatment of venous thromboembolism in patients with or without an inherited hypercoagulable state.

Health disparities and chronic disease associated with anemia in free clinics: A retrospective study of uninsured patients in Tampa Bay.

Objectives: The objective of this study was to assess the diagnosis and management of anemic patients in free clinics around the Tampa Bay area.Methods: In this retrospective study we extracted data including demographics, chronic diseases, and laboratory values from medical charts of uninsured patients seen in 9 free clinics from January 2016 through December 2017 in the Tampa Bay area, FL, USA. Multiple logistic regression analysis was used to assess relationships between socioeconomic variables and a documented history of anemia.Results: From two years of documented data, 6971 patients were included, of which 367 (5%) had a documented diagnosis of anemia. Most were women (315, 86%), and the median age was 41 years (6-91). Among the 367 patients with anemia,191 (52%) patients had an unspecified type of anemia, 144 (39%) were diagnosed with IDA, 16 (4%) with anemia of chronic disease, and the remaining were other uncommon causes. Only 67% (97/144) of IDA patients had documented iron replacement. Colonoscopies were documented in only 32 (9%) of all patients with anemia, and in 23 (16%) IDA patients. Several chronic diseases were statistically associated and comorbid with a diagnosis of anemia.Conclusions: Uninsured patients with IDA are prescribed iron and undergo colonoscopies at sub-optimal rates. Increasing resources, awareness, and education of providers in these settings could lead to improved treatment practices and decrease the risk of morbidity and mortality.

Deletion of the short arm of chromosome 1 (del 1p) is a strong predictor of poor outcome in myeloma patients undergoing an autotransplant.

Several chromosomal abnormalities detected by conventional cytogenetic analysis have an adverse impact on the outcome in myeloma patients. A wide spectrum of abnormalities involving chromosomes 1, 13, 14, and 17 has been described. We analyzed the outcome of 83 patients with clonal cytogenetic abnormalities, who underwent high-dose therapy and autologous stem cell transplantation for multiple myeloma at our institution. Clonal abnormalities were detected at diagnosis by conventional cytogenetic analysis in 83 patients. Patients underwent a single autologous transplant between April 2000 and May 2005. Preparative regimen was high-dose melphalan alone (73), or a combination of topotecan, melphalan, and cyclophosphamide (TMC=10). The most commonly observed chromosomal abnormalities were deletion of chromosome 13 (32%), hyperdiploidy (21%), deletion of chromosome 1p (18%), and t (11; 14) in 7% patients. Median follow-up among surviving patients was 25.5 months. Median interval from diagnosis to autotransplant was 7.7 months (range: 2.5-52). Median progression-free survival (PFS) for the entire group was 19 months and the median overall survival (OS) was 52 months. On univariate analysis, both PFS and OS were significantly shorter in patients with deletion 1p (P=.001 and <.0001, respectively). Thirty-two patients whose cytogenetic abnormalities returned to normal prior to autotransplant had longer PFS and OS than patients with persistent abnormalities (P=.02 and .08, respectively). Deletion 1p is associated with a significantly shorter remission and survival in patients undergoing high-dose therapy and a single autologous transplant for myeloma.