Knowledge-Based Tweet Classification for Disease Sentiment Monitoring

Disease monitoring and tracking is of tremendous value, not only for containing the spread of contagious diseases but also for avoiding unnecessary public concerns and even panic. In this chapter, we present a near real-time sentiment analysis service of public health-related tweets. Traditionally, it is impossible for humans to effectively measure the degree of public health concerns due to limited resources and significant time delays. To solve this problem, we have developed a computational intelligence approach for Epidemic Sentiment Monitoring System (ESMOS) to automatically analyze the disease sentiments and gauge the Measure of Concern (MOC) expressed by Twitter users. More specifically, we present a knowledge-based approach that employs a disease ontology to detect the outbreak of diseases and to analyze the linguistic expressions that convey subjective expressions and sentiment polarity of emotions, feelings, opinions, personal attitudes, etc. with a sentiment classifier. The two-step sentiment classification method utilizes the subjective vocabulary corpus (MPQA), sentiment strength corpus (AFINN), as well as emoticons and profanity words that are often used in social media postings. It first automatically classifies the tweets into personal and non-personal classes, eliminating many tweets such as non-personal “retweets” of news articles from further consideration. In the second stage, the personal tweets are classified into Negative and non-Negative sentiments. In addition, we present a model to quantify the public’s Measure of Concern (MOC) about a disease, based on sentiment classification results. The trends of the public MOC are visualized on a timeline. Correlation analyses between MOC timeline and disease-related sentiment category timelines show that the peaks of the MOC are weakly correlated with the peaks of the News timeline without any appreciable time delay or lead. Our sentiment analysis method and the MOC trend analyses can be generalized to other topical domains, such as mental health monitoring and crisis management. We present the ESMOS prototype for public health-related disease monitoring, for public concern trending and for mapping analyses

Review of phase I and II trials for Wilms' tumour - Can we optimise the search for novel agents?

Survival rates for patients with Wilms' tumour (WT) approximate 90% with refined use of currently available interventions. However, a subgroup of patients, with initial high-risk histopathology or relapsing disease, have a poor prognosis, and it is a challenge to identify and prioritise the development of new innovative approaches for these subgroups. We conducted a systematic literature search for published phase I and II clinical trials that registered patients with WTs and characterised the early phase trial activity, quantified response rates and highlighted avenues for further development. We identified 63 trials (48 phase I, three phase I/II, and 12 phase II trials) enrolling 214 patients with WTs, alongside other malignancies. The number of annually recruited WTs did not change significantly and was less than 20% of the potential candidates. The vast majority of the trials were conducted in North America, and 56 different interventions were investigated, including conventional chemotherapy and biologically targeted therapies. Overall, 33 WTs revealed some degree of tumour control. Of these, five patients demonstrated complete remission (2%), 15 patients partial response (7%) and 13 patients stable disease (6%). None of the included novel biologically targeted therapies emerged as promising interventions, and only conventional chemotherapy was able to induce a complete and partial response. We conclude that early phase trial recruitment of WTs is below expected levels, and the clinical outcome of the included patients is dismal. Improvement of the availability and recruitment to early phase trials for WTs, especially in Europe, is needed

Wilms tumour

Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and evaluation of newer surgical procedures are key areas for future research

Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014

During March–May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2–May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks

Successful treatment by exchange transfusion of a young infant with sodium nitroprusside poisoning

Although sodium nitroprusside (SNP) is often used in pediatric intensive care units, cyanide toxicity can occur after SNP treatment. To treat SNP-induced cyanide poisoning, antidotes such as amyl nitrite, sodium nitrite, sodium thiosulfate, and hydroxycobalamin should be administered immediately after diagnosis. Here, we report the first case of a very young infant whose SNP-induced cyanide poisoning was successfully treated by exchange transfusion. The success of this alternative method may be related to the fact that exchange transfusion not only removes the cyanide from the blood but also activates detoxification systems by supplying sulfur-rich plasma. Moreover, exchange transfusion replaces cyanide-contaminated erythrocytes with fresh erythrocytes, thereby improving the blood's oxygen carrying capacity more rapidly than antidote therapy. Therefore, we believe that exchange transfusion might be an effective therapeutic modality for critical cases of cyanide poisoning

Controversies concerning the diagnosis and treatment of bipolar disorder in children

This commentary grows out of an interdisciplinary workshop focused on controversies surrounding the diagnosis and treatment of bipolar disorder (BP) in children. Although debate about the occurrence and frequency of BP in children is more than 50 years old, it increased in the mid 1990s when researchers adapted the DSM account of bipolar symptoms to diagnose children. We offer a brief history of the debate from the mid 90s through the present, ending with current efforts to distinguish between a small number of children whose behaviors closely fit DSM criteria for BP, and a significantly larger number of children who have been receiving a BP diagnosis but whose behaviors do not closely fit those criteria. We agree with one emerging approach, which gives part or all of that larger number of children a new diagnosis called Severe Mood Dysregulation or Temper Dysregulation Disorder with Dysphoria

Expression of p21WAF1 in Astler–Coller stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy

In several, but not all, previous studies, positive p21WAF1 expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21WAF1 expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler–Coller stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21WAF1 was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21WAF1 was associated with DFS (p = 0.025) and OS (p = 0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained the only independent prognostic parameter in relation to DFS and OS (p = 0.035 and p = 0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21WAF1 expression but not in the subgroup of 61 stage B2 patients with negative p21WAF1 expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, p = 0.03) and OS (96% versus 82%, p = 0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21WAF1 expression was also associated with better DFS and OS (p = 0.03, p = 0.002, respectively). Expression of p21WAF1 in colorectal tumor cells identifies a subgroup of Astler–Coller stage B2 patients who could benefit significantly from 5FU-based chemotherapy and may improve the selection of patients for adjuvant chemotherapy

Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma

<p>Abstract</p> <p>Background</p> <p>Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC).</p> <p>Methods</p> <p>An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluated <it>in vitro</it>. In addition, the <it>in vivo </it>effect of TS siRNA on tumor progression was assessed using a xenograft model.</p> <p>Results</p> <p>Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model.</p> <p>Conclusion</p> <p>TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.</p

Impact of Circulating Cholesterol Levels on Growth and Intratumoral Androgen Concentration of Prostate Tumors

Prostate cancer (PCa) is the second most common cancer in men. Androgen deprivation therapy (ADT) leads to tumor involution and reduction of tumor burden. However, tumors eventually reemerge that have overcome the absence of gonadal androgens, termed castration resistant PCa (CRPC). Theories underlying the development of CRPC include androgen receptor (AR) mutation allowing for promiscuous activation by non-androgens, AR amplification and overexpression leading to hypersensitivity to low androgen levels, and/or tumoral uptake and conversion of adrenally derived androgens. More recently it has been proposed that prostate tumor cells synthesize their own androgens through de novo steroidogenesis, which involves the step-wise synthesis of androgens from cholesterol. Using the in vivo LNCaP PCa xenograft model, previous data from our group demonstrated that a hypercholesterolemia diet potentiates prostatic tumor growth via induction of angiogenesis. Using this same model we now demonstrate that circulating cholesterol levels are significantly associated with tumor size (R = 0.3957, p = 0.0049) and intratumoral levels of testosterone (R = 0.41, p = 0.0023) in LNCaP tumors grown in hormonally intact mice. We demonstrate tumoral expression of cholesterol uptake genes as well as the spectrum of steroidogenic enzymes necessary for androgen biosynthesis from cholesterol. Moreover, we show that circulating cholesterol levels are directly correlated with tumoral expression of CYP17A, the critical enzyme required for de novo synthesis of androgens from cholesterol (R = 0.4073, p = 0.025) Since hypercholesterolemia does not raise circulating androgen levels and the adrenal gland of the mouse synthesizes minimal androgens, this study provides evidence that hypercholesterolemia increases intratumoral de novo steroidogenesis. Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the growth of prostate tumors, and suggest that treatment of CRPC may be optimized by inclusion of cholesterol reduction therapies in conjunction with therapies targeting androgen synthesis and the AR