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Background: Radiotherapy is associated with a high risk of heart disease in patients with left-sided breast cancer. Previously, the entire heart was considered an organ at risk (OAR) during planning. Studies have shown that the effect of radiation therapy depends on the dose to specific heart substructures. However, the tolerance dose of the left anterior descending coronary artery (LAD), an important cardiac substructure, is yet to be determined. This study aims to verify the feasibility of reducing the LAD dose with appropriate dose-volume constraints for patients undergoing left whole-breast radiotherapy, without compromising the target dose coverage, using tomotherapy techniques.Method: This retrospective study generated tomohelical and tomodirect plans initially without considering the LAD as OAR in the treatment planning. To reduce the LAD dose, plans were regenerated by including the LAD as an OAR with appropriate dose constraints. The dose-volume histogram parameters of these plans were compared with those of the initial plans of the respective types.Results: Tomohelical plans showed a 4.4% reduction in maximum dose and a 3.8% reduction in V15 for LAD, while tomodirect plans registered a 3% reduction in V15, with the conformity index remaining constant. Based on the LAD dosimetric results, considering the LAD as an OAR is associated with lower LAD doses without compromising the target volume coverage.Conclusion: It is feasible to reduce the LAD dose without compromising target volume coverage or affecting other OAR doses in patients with left breast cancer, using tomotherapy techniques.

COVID-19 has sparked a global pandemic, with a variety of inflamed instances and deaths increasing on an everyday basis. Researchers are actively increasing and improving distinct mathematical and ML algorithms to forecast the infection. The prediction and detection of the Omicron variant of COVID-19 brought new issues for the health fraternity due to its ubiquity in human beings. In this research work, two learning algorithms, namely, deep learning (DL) and machine learning (ML), were developed to forecast the Omicron virus infections. Automatic disease prediction and detection have become crucial issues in medical science due to rapid population growth. In this research study, a combined Extended CNN-RNN research model was developed on a chest CT-scan image dataset to predict the number of +ve and −ve cases of Omicron virus infections. The proposed research model was evaluated and compared against the existing system utilizing a dataset of 16,733-sample training and testing CT-scan images collected from the Kaggle repository. This research article aims to introduce a combined ML and DL technique based on the combination of an Extended Convolutional Neural Network (ECNN) and an Extended Recurrent Neural Network (ERNN) to diagnose and predict Omicron virus-infected cases automatically using chest CT-scan images. To overcome the drawbacks of the existing system, this research proposes a combined research model that is ECNN-ERNN, where ECNN is used for the extraction of deep features and ERNN is used for exploration using extracted features. A dataset of 16,733 Omicron computer tomography images was used as a pilot assessment for this proposed prototype. The investigational experiment results show that the projected prototype provides 97.50% accuracy, 98.10% specificity, 98.80% of AUC, and 97.70% of F1-score. To the last, the study outlines the advantages being offered by the proposed model with respect to other existing models by comparing different parameters of validation such as accuracy, error rate, data size, time complexity, and execution time.

Abstract Background Antibiotic resistant S. aureus infection is a global threat. Newer approaches are required to control this organism in the current scenario. Cell wall degrading enzymes have been proposed as antibacterial agents for human therapy. P128 is a novel antistaphylococcal chimeric protein under development against S. aureus for human use which derives its bacterial cell wall degrading catalytic endopeptidase domain from ORF56, the Phage K tail-structure associated enzyme. Lead therapeutic entities have to be extensively characterized before they are assessed in animals for preclinical safety and toxicity. P128 is effective against antibiotic resistant strains as well as against a panel of isolates of global significance. Its efficacy against S. aureus in vivo has been established in our lab. Against this background, this study describes the characterization of this protein for its biochemical properties and other attributes. Results We evaluated the requirement or effect of divalent cations and the metal ion chelator, EDTA upon biological activity of P128. As the protein is intended for therapeutic use, we tested its activity in presence of body fluids and antibodies specific to P128. For the same reason, we used standard human cell lines to evaluate cytotoxic effects, if any. The divalent cations, calcium and magnesium at upto 25 mM and Zinc upto 2.5 mM neither inhibited nor enhanced P128 activity. Incubation of this protein with EDTA, human serum, plasma and blood also did not alter the antibacterial properties of the molecule. No inhibitory effect was observed in presence of hyper-immune sera raised against the protein. Finally, P128 did not show any cytotoxic effect on HEp2 and Vero cells at the highest concentration (5 mg/mL) tested. Conclusions The results presented here throw light on several properties of protein P128. Taken together, these substantiate the potential of P128 for therapeutic use against S. aureus. Further development of the protein and conduct of preclinical safety studies in animals is warranted.

Passive acoustic monitoring is a promising tool for monitoring at-risk populations of vocal species, yet, extracting relevant information from large acoustic datasets can be time-consuming, creating a bottleneck at the point of analysis. To address this, an open-source framework for deep learning in bioacoustics to automatically detect Bornean white-bearded gibbon (Hylobates albibarbis) "great call" vocalizations in a long-term acoustic dataset from a rainforest location in Borneo is adapted. The steps involved in developing this solution are described, including collecting audio recordings, developing training and testing datasets, training neural network models, and evaluating model performance. The best model performed at a satisfactory level (F score = 0.87), identifying 98% of the highest-quality calls from 90 h of manually annotated audio recordings and greatly reduced analysis times when compared to a human observer. No significant difference was found in the temporal distribution of great call detections between the manual annotations and the model's output. Future work should seek to apply this model to long-term acoustic datasets to understand spatiotemporal variations in H. albibarbis' calling activity. Overall, a roadmap is presented for applying deep learning to identify the vocalizations of species of interest, which can be adapted for monitoring other endangered vocalizing species., (© 2024 Acoustical Society of America.)

Passive acoustic monitoring (PAM) is a powerful tool for studying ecosystems. However, its effective application in tropical environments, particularly for insects, poses distinct challenges. Neotropical katydids produce complex species-specific calls, spanning mere milliseconds to seconds and spread across broad audible and ultrasonic frequencies. However, subtle differences in inter-pulse intervals or central frequencies are often the only discriminatory traits. These extremities, coupled with low source levels and susceptibility to masking by ambient noise, challenge species identification in PAM recordings. This study aimed to develop a deep learning-based solution to automate the recognition of 31 katydid species of interest in a biodiverse Panamanian forest with over 80 katydid species. Besides the innate challenges, our efforts were also encumbered by a limited and imbalanced initial training dataset comprising domain-mismatched recordings. To overcome these, we applied rigorous data engineering, improving input variance through controlled playback re-recordings and by employing physics-based data augmentation techniques, and tuning signal-processing, model and training parameters to produce a custom well-fit solution. Methods developed here are incorporated into Koogu, an open-source Python-based toolbox for developing deep learning-based bioacoustic analysis solutions. The parametric implementations offer a valuable resource, enhancing the capabilities of PAM for studying insects in tropical ecosystems. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Night-time light can have profound ecological effects, even when the source is natural moonlight. The impacts of light can, however, vary substantially by taxon, habitat and geographical region. We used a custom machine learning model built with the Python package Koogu to investigate the in situ effects of moonlight on the calling activity of neotropical forest katydids over multiple years. We prioritised species with calls that were commonly detected in human annotated data, enabling us to evaluate model performance. We focused on eight species of katydids that the model identified with high precision (generally greater than 0.90) and moderate-to-high recall (minimum 0.35), ensuring that detections were generally correct and that many calls were detected. These results suggest that moonlight has modest effects on the amount of calling, with the magnitude and direction of effect varying by species: half of the species showed positive effects of light and half showed negative. These findings emphasize the importance of understanding natural history for anticipating how biological communities respond to moonlight. The methods applied in this project highlight the emerging opportunities for evaluating large quantities of data with machine learning models to address ecological questions over space and time. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Vanishing bile duct syndrome is an uncommon condition characterised by the progressive loss and disappearance of bile ducts. It is an acquired form of cholestatic liver disease presenting with hepatic ductopenia (loss of >50% bile ducts in the portal areas). We present a case of vanishing bile duct syndrome as a presentation of Hodgkin's lymphoma who was treated with standard-of-care chemotherapy-doxorubicin, bleomycin, vinblastine and dacarbazine (along with brief administration of rituximab), which led to complete response and normalisation of liver function., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Vocal complexity is central to many evolutionary hypotheses about animal communication. Yet, quantifying and comparing complexity remains a challenge, particularly when vocal types are highly graded. Male Bornean orangutans ( Pongo pygmaeus wurmbii ) produce complex and variable "long call" vocalizations comprising multiple sound types that vary within and among individuals. Previous studies described six distinct call (or pulse) types within these complex vocalizations, but none quantified their discreteness or the ability of human observers to reliably classify them. We studied the long calls of 13 individuals to: (1) evaluate and quantify the reliability of audio-visual classification by three well-trained observers, (2) distinguish among call types using supervised classification and unsupervised clustering, and (3) compare the performance of different feature sets. Using 46 acoustic features, we used machine learning ( i.e. , support vector machines, affinity propagation, and fuzzy c-means) to identify call types and assess their discreteness. We additionally used Uniform Manifold Approximation and Projection (UMAP) to visualize the separation of pulses using both extracted features and spectrogram representations. Supervised approaches showed low inter-observer reliability and poor classification accuracy, indicating that pulse types were not discrete. We propose an updated pulse classification approach that is highly reproducible across observers and exhibits strong classification accuracy using support vector machines. Although the low number of call types suggests long calls are fairly simple, the continuous gradation of sounds seems to greatly boost the complexity of this system. This work responds to calls for more quantitative research to define call types and quantify gradedness in animal vocal systems and highlights the need for a more comprehensive framework for studying vocal complexity vis-à-vis graded repertoires., Competing Interests: The authors declare there are no competing interests., (©2024 Erb et al.)

Background: Current protocols for bedside swallow evaluation have high rates of false negative results. Though experts are not consistently able to screen for aspiration risk by assessing vocal quality, there is emerging evidence that vocal acoustic parameters are significantly different in patients at risk of aspiration. Herein, we aimed to determine whether the presence of material on the vocal folds in an excised canine laryngeal model may have an impact on acoustic and aerodynamic measures., Methods: Two ex vivo canine larynges were tested. Three liquids of different viscosities (1:100 diluted glycerin, pure glycerin, and honey-thick Varibar) were placed on the vocal folds at a constant volume. Acoustic and aerodynamic measures were obtained in both adducted and abducted vocal fold configurations. Intraglottal high-speed imaging was used to approximate the maximum divergence angle of the larynges in the studied conditions and examine its relationship to vocal efficiency (VE) and acoustic measures., Results: In glottic insufficiency conditions only, we found that several acoustic parameters could predict the presence of material on the vocal folds. Based on the combination of the aerodynamic and acoustic data, we found that decreased spectral energy in the higher harmonics was associated with decreased VE in the presence of material on the vocal folds and/or glottic insufficiency., Conclusion: Decreased spectral energy in the higher harmonics of the voice was found to be a potential biomarker of swallowing dysfunction, as it correlates with decreased vocal efficiency due to material on the vocal folds and/or glottic insufficiency, both of which are known risk factors for aspiration., Level of Evidence: NA Laryngoscope, 133:2517-2524, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Early postoperative mortality risk prediction is crucial for clinical management of gastric cancer. This study aims to predict 90-day mortality in gastric cancer patients undergoing gastrectomy using automated machine learning (AutoML), optimize models for preoperative prediction, and identify factors influential in prediction. National Cancer Database was used to identify stage I-III gastric cancer patients undergoing gastrectomy between 2004 and 2016. 26 features were used to train predictive models using H2O.ai AutoML. Performance on validation cohort was measured. In 39,108 patients, 90-day mortality rate was 8.8%. The highest performing model was an ensemble (AUC = 0.77); older age, nodal ratio, and length of inpatient stay (LOS) following surgery were most influential for prediction. Removing the latter two parameters decreased model performance (AUC 0.71). For optimizing models for preoperative use, models were developed to first predict node ratio or LOS, and these predicted values were inputted for 90-day mortality prediction (AUC of 0.73-0.74). AutoML performed well in predicting 90-day mortality in a larger cohort of gastric cancer patients that underwent gastrectomy. These models can be implemented preoperatively to inform prognostication and patient selection for surgery. Our study supports broader evaluation and application of AutoML to guide surgical oncologic care., (© 2023. The Author(s).)

Background: An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality of life (QOL). We compared QOL in patients enrolled to SWOG S1400I, a substudy of the LungMAP biomarker-driven master protocol., Methods: SWOG S1400I was a randomized phase III trial comparing nivolumab plus ipilimumab vs nivolumab for treatment of immunotherapy-naïve disease in advanced squamous cell lung cancer. The primary endpoint was the MD Anderson Symptom Inventory-Lung Cancer severity score at week 7 and week 13 with a target difference of 1.0 points, assessed using multivariable linear regression. A composite risk model for progression-free and overall survival was derived using best-subset selection., Results: Among 158 evaluable patients, median age was 67.6 years and most were male (66.5%). The adjusted MD Anderson Symptom Inventory-Lung Cancer severity score was 0.04 points (95% confidence interval [CI] = -0.44 to 0.51 points; P = .89) at week 7 and 0.12 points (95% CI = -0.41 to 0.65; P = .66) at week 13. A composite risk model showed that patients with high levels of appetite loss and shortness of breath had a threefold increased risk of progression or death (hazard ratio [HR] = 3.06, 95% CI = 1.88 to 4.98; P < .001) and that those with high levels of both appetite loss and work limitations had a fivefold increased risk of death (HR = 5.60, 95% CI = 3.27 to 9.57; P < .001)-compared with those with neither risk category., Conclusions: We found no evidence of a benefit of ipilimumab added to nivolumab compared with nivolumab alone for QOL in S1400I. A risk model identified patients at high risk of poor survival, demonstrating the prognostic relevance of baseline patient-reported outcomes even in those with previously treated advanced cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Triple-negative breast cancer (TNBC) is classically defined by estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry expression <1% and absence of HER2 amplification/overexpression. HER2-negative breast cancer with low ER/PR expression (1-10%) has a gene expression profile similar to TNBC; however, real-world treatment patterns, chemotherapy response, endocrine therapy benefit, and survival outcomes for the Low-ER group are not well known. 516 patients with stage I-III HER2-negative breast cancer and ER/PR expression ≤10% who were enrolled in a multisite prospective registry between 2011 and 2019 were categorized on the basis of ER/PR expression. TNBC (ER and PR < 1%) and Low-ER (ER and/or PR 1-10%) groups comprised 87.4% (n = 451) and 12.6% (n = 65) of patients, respectively. Demographic, clinical, and treatment characteristics, including prevalence of germline BRCA1/2 mutation, racial and ethnic distribution, and chemotherapy use were not different between TNBC and Low-ER groups. No difference was observed in recurrence-free survival (RFS) and overall survival (OS) between TNBC and Low-ER groups (3-year RFS 82.5% versus 82.4%, respectively, p = 0.728; 3-year OS 88.0% versus 83.4%, respectively, p = 0.632). Among 358 patients receiving neoadjuvant chemotherapy, rates of pathologic complete response were similar for TNBC and Low-ER groups (49.2% vs 51.3%, respectively, p = 0.808). The HER2-negative Low-ER group is often excluded from TNBC clinical trials assessing novel treatments (immunotherapy and antibody-drug conjugates), thus limiting efficacy data for newer effective therapies in this group. Given that HER2-negative Low-ER disease displays clinical characteristics and outcomes similar to TNBC, inclusion of this group in TNBC clinical trials is encouraged., (© 2022. The Author(s).)

The bite of a brown recluse spider ( Loxosceles reclusa ) is usually associated with skin necrosis; however, it can lead to more significant morbidity including acute hemolytic anemia, rhabdomyolysis, disseminated intravascular coagulopathy and death. Here we highlight a case using plasmapheresis as treatment for acute hemolytic anemia caused by the bite of a brown recluse spider. A 49-year-old male presented to the emergency room 5 days after suffering a spider bite due to worsening symptoms. He had worsening pain at the site of the bite, diffuse body myalgias, darkening of his urine, chills, and shortness of breath. Hematology was consulted to assist in the management of hemolytic anemia refractory to multiple blood transfusions, worsening acute kidney failure requiring hemodialysis, and concern for impending death. After a literature review suggesting plasmapheresis may be beneficial in this scenario, the case was discussed with the local blood bank, and plasmapheresis was initiated. The patient underwent plasmapheresis with albumin for 2 days and the patient's hemoglobin improved and stabilized. Therapy of loxoscelism is directed at limiting the dermatonecrosis at the site of the envenomation and in cases of systemic illness supportive care is recommended. Therapeutic plasma exchange has been shown efficacious in treating snake envenomation, but there are limited data detailing its use for brown recluse spider envenomation. Here we present a case to highlight the benefit of plasmapheresis in a patient with acute hemolytic anemia secondary to a brown recluse spider bite., Competing Interests: None to declare., (Copyright 2022, Harry et al.)

Background: Psychological distress is common in patients with cancer. Distress can affect patients' engagement with treatment. We examined the relationship between psychological distress and treatment timeliness in a sample of adult oncology patients at a safety-net hospital., Methods: A retrospective review was conducted of all patients screened for distress at a first outpatient oncology visit between March 1, 2014, and December 31, 2015 (n=500). The analytic sample (n=96) included patients with a new cancer diagnosis and a curative-intent treatment plan for lymphoma (stage I-IV), solid tumor malignancy (stage I-III), or head and neck cancer (stage I-IVb). Distress was measured using the Hospital Anxiety and Depression Scale. Using Poisson regression, we determined the effects of depression and anxiety on treatment timeliness. Patient age, sex, race/ethnicity, insurance type, cancer site, and cancer stage were included as covariates., Results: Mean patient age was 54 years. The median treatment initiation interval was 28 days. Clinically significant anxiety was present in 34% of the sample, and clinically significant depression in 15%. Greater symptom severity in both anxiety and depression were associated with a longer treatment initiation interval after controlling for demographics and disease factors. The average days to treatment (DTT) was 4 days longer for patients with elevated anxiety scores and for those with elevated depression scores compared with those without. Overall survival was not associated with anxiety, depression, or DTT., Conclusions: In this safety-net patient sample, greater psychological distress was associated with slower time to treatment. As of writing, this is a new finding in the literature, and as such, replication studies utilizing diverse samples and distress measurement tools are needed.

Many animals rely on long-form communication, in the form of songs, for vital functions such as mate attraction and territorial defence. We explored the prospect of improving automatic recognition performance by using the temporal context inherent in song. The ability to accurately detect sequences of calls has implications for conservation and biological studies. We show that the performance of a convolutional neural network (CNN), designed to detect song notes (calls) in short-duration audio segments, can be improved by combining it with a recurrent network designed to process sequences of learned representations from the CNN on a longer time scale. The combined system of independently trained CNN and long short-term memory (LSTM) network models exploits the temporal patterns between song notes. We demonstrate the technique using recordings of fin whale ( Balaenoptera physalus ) songs, which comprise patterned sequences of characteristic notes. We evaluated several variants of the CNN + LSTM network. Relative to the baseline CNN model, the CNN + LSTM models reduced performance variance, offering a 9-17% increase in area under the precision-recall curve and a 9-18% increase in peak F1-scores. These results show that the inclusion of temporal information may offer a valuable pathway for improving the automatic recognition and transcription of wildlife recordings.

Purpose: Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response (pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in triple-negative breast cancer (TNBC). Aim of the NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens., Patients and Methods: Patients aged ≥18 years with stage I-III TNBC were randomized (1:1) to receive either paclitaxel (P) weekly × 12 plus carboplatin AUC6 every 21 days × 4 followed by doxorubicin/cyclophosphamide (AC) every 14 days × 4 (CbP → AC, arm A), or carboplatin AUC6 + docetaxel (D) every 21 days × 6 (CbD, arm B). Stromal tumor-infiltrating lymphocytes (sTIL) were assessed. Primary endpoint was pCR in breast and axilla. Other endpoints included residual cancer burden (RCB), toxicity, cost, and event-free (EFS) and overall survival (OS)., Results: One hundred patients were randomized; arm A ( n = 48) or arm B ( n = 52). pCR was 54% [95% confidence interval (CI), 40%-69%] in arm A and 54% (95% CI, 40%-68%) in arm B. RCB 0+I rate was 67% in both arms. Median sTIL density was numerically higher in those with pCR compared with those with residual disease (20% vs. 5%; P = 0.25). At median follow-up of 38 months, EFS and OS were similar in the two arms. Grade 3/4 adverse events were more common in arm A compared with arm B, with the most notable differences in neutropenia (60% vs. 8%; P < 0.001) and febrile neutropenia (19% vs. 0%; P < 0.001). There was one treatment-related death (arm A) due to acute leukemia. Mean treatment cost was lower for arm B compared with arm A ( P = 0.02)., Conclusions: The two-drug CbD regimen yielded pCR, RCB 0+I, and survival rates similar to the four-drug regimen of CbP → AC, but with a more favorable toxicity profile and lower treatment-associated cost., (©2020 American Association for Cancer Research.)

Multiple myeloma is a plasma cell neoplasm characterized by clonal proliferation of immunoglobulin producing terminally differentiated B cells. Classically patients are described to present with bone pain, hypercalcemia, anemia, and/or renal impairment. A less described clinical manifestation related to the myeloma is acquired coagulation abnormalities including paraprotein interfering with the coagulation cascade or exhibiting specific antibody activity. Factor X deficiency is reported in patients with secondary amyloidosis. We describe a patient who presented with bleeding tendency and an abnormal prothrombin and activated partial thromboplastin times (PT/PTT) due to factor X deficiency. A thorough workup revealed the diagnosis of multiple myeloma with the presence of monoclonal lambda light chain restricted plasma cells with qualifying end-organ damage without evidence of amyloidosis. Prior to the ultimate diagnosis, the patient succumbed to septic shock and acute respiratory distress syndrome due to Streptococcus Pneumonia infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Sabobeh et al.)

Automatically detecting animal signals in soundscape recordings is of benefit to passive acoustic monitoring programs which may be undertaken for research or conservation. Numerous algorithms exist, which are typically optimized for certain situations (i.e., certain animal sound types and ambient noise conditions). Adding to the library of algorithms, this paper developed, tested, and compared three detectors for Omura's whale vocalizations (15-62 Hz; <15 s) in marine soundscape recordings which contained noise from other animals, wind, earthquakes, ships, and seismic surveys. All three detectors were based on processing of spectrographic representations. The specific methods were spectrogram cross-correlation, entropy computation, and spectral intensity "blob" tracing. The latter two were general-purpose detectors that were adapted for detection of Omura's whale vocalizations. Detector complexity and post-processing effort varied across the three detectors. Performance was assessed qualitatively using demonstrative examples, and quantitatively using Receiver-Operating Characteristics and Precision-Recall curves. While the results of quantitative assessment were dominated by the spectrogram cross-correlation method, qualitative assessment showed that all three detectors offered promising performance.

Extraction of tonal signals embedded in background noise is a crucial step before classification and separation of low-frequency sounds of baleen whales. This work reports results of comparing five tonal detectors, namely the instantaneous frequency estimator, YIN estimator, harmonic product spectrum, cost-function-based detector, and ridge detector. Comparisons, based on a low-frequency adaptation of the Silbido scoring feature, employ five metrics, which quantify the effectiveness of these detectors to retrieve tonal signals that have a wide range of signal to noise ratios (SNRs) and the quality of the detection results. Ground-truth data were generated by embedding 20 synthetic Antarctic blue whale (Balaenoptera musculus intermedia) calls in randomly extracted 30-min noise segments from a 79 h-library recorded by an Ocean Bottom Seismometer in the Indian Ocean during 2012-2013. Monte-Carlo simulations were performed using 20 trials per SNR, ranging from 0 dB to 15 dB. Overall, the tonal detection results show the superiority of the cost-function-based and the ridge detectors, over the other detectors, for all SNR values. More particularly, for lower SNRs (⩽3 dB), these two methods outperformed the other three with high recall, low fragmentation, and high coverage scores. For SNRs ⩾7 dB, the five methods performed similarly.

BACKGROUND Rituximab is a chimeric monoclonal antibody to CD20 that is used to treat vasculitis, B-cell lymphoproliferative disorders, and B-cell non-Hodgkin lymphoma (NHL). A report is presented of a case of rituximab-induced acute thrombocytopenia (RIAT) in a woman with splenic marginal zone lymphoma (SMZL) and chronic hepatitis C virus (HCV) infection. CASE REPORT A 46-year-old woman with SMZL complicated by chronic HCV infection presented with worsening B symptoms of fever, night sweats, and loss of weight. The patient had a history of recreational drug use. Intravenous treatment with rituximab (dose, 375 mg/m²) commenced with close monitoring in hospital. On the following day, the complete blood count (CBC) showed that her platelet count had dropped from her admission level of 167,000/μl to 7,000/μl, with no change in hemoglobin or white blood cell (WBC) levels. A diagnosis of RIAT was made. The patient was managed conservatively and monitored for the development of potential clinical complications. CONCLUSIONS RIAT is a rare complication of treatment with rituximab and may be poorly recognized. Further studies are needed to determine the incidence and causes of thrombocytopenia in patients treated with rituximab and the possible association with chronic viral infections, including HCV.

Anemia is a common finding in alcoholics. It is often multifactorial and caused by a combination of liver dysfunction, ineffective erythropoiesis, and poor nutrition. Zieve's syndrome (ZS) is a clinical syndrome that presents with a triad of jaundice, hemolytic anemia, and hyperlipidemia secondary to alcohol use. Herein, we present a case of a 58-year-old male with a history of liver cirrhosis who presented after a fall due to binge drinking and was found to have severe anemia. Workup was consistent with hemolytic anemia with no source of active bleeding. The patient was managed with supportive treatment and blood transfusions which improved his anemia. However, given his advanced liver disease, he developed encephalopathy and subsequently severe aspiration pneumonia. He died 18 days after admission., Competing Interests: The authors have declared that no competing interests exist.

Background: Non-daily smokers (NDS) who smoke on some but not all days are a growing subset of United States (US) tobacco users. Racial/ethnic minorities are more likely to be NDS. African American NDS have strikingly high levels of nicotine and carcinogen exposure, making treatment of this high risk group a priority., Methods: The current study is one of three ongoing federally-funded clinical trials of NDS and, to our knowledge the only RCT focused on racial/ethnic minority NDS. The design has been guided by input from Patient and Stakeholder Advisory Panels who helped develop the research questions, design the intervention, and select the outcomes. The objective is to compare the effectiveness of smoking cessation counseling alone (C) or smoking cessation counseling plus participant's choice of nicotine replacement therapy (NRT; C + NRT) for African American NDS. Two-hundred seventy-eight African American NDS will be randomized in a 2:1 fashion to C + NRT or C. All participants receive five sessions of smoking cessation counseling; those randomized to C + NRT receive their choice of nicotine gum, patch, and/or lozenge. Treatment in both groups lasts for 12 weeks. We hypothesize that C + NRT will be more effective than C on the primary outcome of biochemically-confirmed abstinence from smoking at week 12. Secondary aims will compare C + NRT and C on patient- and provider-desired outcomes including abstinence from smoking at week 26, change in biochemically-verified nicotine and carcinogen exposure, days abstinent, and treatment process measures (e.g., NRT use and side effects). Predictors of abstinence will also be explored., Discussion: Findings will illuminate effective treatment options for African American NDS and contribute to development of evidence-based guidelines for treating the 8.9 million US adult NDS for whom no guidelines currently exist., Trial Registration Number: ClinicalTrials.gov: NCT02244918., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome that presents with neurological manifestations, including seizures, headache, or confusion, and is associated with posterior cerebral white matter edema on imaging. PRES is typically a benign and reversible condition. However, PRES can be fatal or associated with permanent deficits. Numerous conditions are associated with PRES, including hypertensive encephalopathy, renal diseases, and cytotoxic or immunosuppressant drugs. Recently, many case reports described the association between PRES and chemotherapeutic agents. However, trastuzumab-associated PRES is rarely reported. Herein, we report a case of a 51-year-old female with a history of metastatic gastric cancer who developed seizures while being treated with trastuzumab, and neuroimaging confirmed the diagnosis of PRES., Competing Interests: The authors have declared that no competing interests exist.

Burkitt lymphoma is cytogenetically characterized by t(8;14)(q24;q32) translocation, sometimes accompanied by additional cytogenetic abnormalities. These abnormalities usually result in more aggressive clinical presentation and morphology of the disease. The current report presens a case of Burkitt lymphoma with t(8;14)(q24;q32) accompanied by partial tetrasomy of chromosome 1(47,XY,+1,i(1)(q10),t(8;14)(q24;q32)[2]/46,XY[18]). The patient was a 59-year-old male who presented with abdominal pain, leukocytosis and tumor lysis syndrome. No lymphadenopathy was noted. Cerebrospinal fluid analysis revealed atypical lymphocytes. A peripheral blood smear revealed tumor cells exhibiting distinct 'blastoid' morphology: Prominent nucleoli, basophilic cytoplasm, occasional cytoplasmic vacuoles. Flow cytometry demonstrated B cells expressing cluster of differentiation (CD)10 and cytoplasmic kappa light chain restriction without surface expression of immunoglobulins and CD20. A bone marrow biopsy revealed hematopoiesis, with a 90% replacement with atypical lymphocytes. The patient was treated with chemotherapy. Following the first cycle of treatment, the patient developed neutropenic fever, bacteremia and died a few days later. Gain of chromosome 1q in addition to characteristic for Burkitt lymphoma t(8;14)(q24;q32) resulted in immature 'blastoid' morphology and the immunophenotype of tumor cells, leukemic presentation without lymph node involvement and a highly aggressive clinical course.

Low-grade follicular lymphomas are genetically characterized by the translocation t(14; 18)(q32;q21) with BCL2 gene rearrangements. Marginal zone lymphomas are often associated with translocations or transcriptional deregulations of the MALT gene. We report 2 cases of lymphomas which harbor both the t(14;18)(q32;q21) translocation and MALT gene upregulation. Patients presented with numerous circulating atypical lymphocytes. Lymph node biopsy in both cases on HE staining demonstrated vague nodularity readily highlighted by CD10, CD23, or BCL6. Staining with CD20 and BCL2 demonstrated monotonous diffuse effacement of normal architecture with tumor cells without obvious follicular structures. Morphologically, tumor cells were consistent with centrocytes. Bone marrow biopsy demonstrated a combined peritrabecular and interstitial distribution of the tumor cells. These cases present substantial difficulties for diagnosis and classification. Clinical and morphological features were mostly consistent with follicular lymphoma, with a few features more often seen in marginal zone lymphomas (leukemic presentation, no CD10 in circulating cells, interstitial location of tumor cells in bone marrow); therefore, these cases were finally classified as follicular lymphoma grade I. Both patients were treated with standard chemotherapy regimens for follicular and nongastric MALT lymphomas with a good response to date., (© 2018 S. Karger AG, Basel.)

Fewer than 5% of cancer patients participate in clinical trials, making it challenging to test new therapies or interventions for cancer. Even within that small number, patients living in inner-city and rural areas are underrepresented in clinical trials. This study explores cancer patients' awareness and perceptions of cancer clinical trials, as well as their perceptions of patient-provider interactions related to discussing cancer clinical trials in order to improve accrual in cancer clinical trials. Interviews with 66 former and current in inner-city and rural cancer patients revealed a lack of awareness and understanding about clinical trials, as well as misconceptions about what clinical trials entail. Findings also revealed that commercials and television shows play a prominent role in forming inner-city and rural patients' attitudes and/or misconceptions about clinical trials. However, rural patients were more likely to hold unfavorable views about clinical trials than inner-city patients. Patient-provider discussions emerged as being crucial for increasing awareness of clinical trials among patients and recruiting them to trials. Findings from this study will inform communication strategies to enhance recruitment to cancer clinical trials by increasing awareness and countering misconceptions about clinical trials.

Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme "HMG CoA reductase" and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta-analysis of 10 studies, statin use was associated with improved recurrence-free survival (RFS; HR 0.64; 95% CI 0.53-0.79, I(2)  = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59-0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44-1.46). Statin users similarly showed improved overall survival in a meta-analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44-0.99, I(2)  = 89%). Statin users also had improved cancer-specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46-1.06, I(2)  = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence-free survival. Statin users also had improved overall survival and cancer-specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified., (© 2016 UICC.)

Double-hit lymphomas (DHL) are defined as B-cell lymphoma with a chromosomal breakpoint affecting the MYC/8q24 locus in combination with rearrangement at (14;18)(q32;q21). We recently observed three cases of B-cell lymphoma with an extra intact MYC signal in association with the t(14;18)(q32;q21) translocation. The impact of an extra copy of MYC to the clinical course and prognosis of one patient with Diffuse Large B Cell Lymphoma (DLBCL) and two patients with Follicular Lymphoma (FL) was evaluated. Flow cytometry in all cases demonstrated lambda- or kappa-light chain restricted CD20 and CD10 positive neoplastic B cells. FISH analysis was negative for MYC gene rearrangement but demonstrated an extra copy of intact MYC. Tissue sections displayed typical starry sky "gray zone" lymphoma morphology in case of DLBCL and FL morphology in cases 2 and 3, with high Ki67 labeling in all three cases. All patients responded well to initial chemotherapy although displayed variant outcome after initial remission. The patient with DLBCL deceased within a year of diagnosis while the other two patients with FL showed much better overall survival. Our limited experience showed that additional copy of intact MYC may be equivalent to "classic" DHL on the background of DLBCL with additional cytogenetic abnormalities, however isolated t(14;18)(q32;q21) translocation in combination with additional copy of intact MYC may demonstrate histology and clinical outcome more comparable with "classic" low grade follicular lymphoma, albeit with more aggressive morphology.

BRAF V600E mutations have been reported in several histiocytic and dendritic cell neoplasms. In this case series, we report BRAF V600E-positive histiocytic and dendritic cell neoplasms in association with lymphomas and lymphoid proliferations. This is a review of cases with immunohistochemistry for BRAF V600E, with additional immunohistochemistry to categorize tumors. We report the first case of BRAF V600E-positive indeterminate cell tumor in association with angioimmunoblastic T-cell lymphoma. We also report a case of BRAF V600E-positive interdigitating dendritic cell sarcoma in a patient with positive B-cell polymerase chain reaction. It is unclear if these neoplasms developed as transdifferentiation of lymphoid neoplasms or if they developed independently. These cases illustrate the expanding spectrum of BRAF V600E-positive histiocytic and dendritic cell tumors and suggest that attention should be paid to lymphomas for possible coincident presentation of these disorders., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Prior research has shown that echolocation clicks of several species of terrestrial and marine fauna can be modelled as Gabor-like functions. Here, a system is proposed for the automatic detection of a variety of such signals. By means of mathematical formulation, it is shown that the output of the Teager-Kaiser Energy Operator (TKEO) applied to Gabor-like signals can be approximated by a Gaussian function. Based on the inferences, a detection algorithm involving the post-processing of the TKEO outputs is presented. The ratio of the outputs of two moving-average filters, a Gaussian and a rectangular filter, is shown to be an effective detection parameter. Detector performance is assessed using synthetic and real (taken from MobySound database) recordings. The detection method is shown to work readily with a variety of echolocation clicks and in various recording scenarios. The system exhibits low computational complexity and operates several times faster than real-time. Performance comparisons are made to other publicly available detectors including pamguard.

Until about 4 years ago, warfarin was the only oral anticoagulant approved in the United States, and switching between oral anticoagulants has become an option since the emergence of the novel oral anticoagulants dabigatran, rivaroxaban, and apixaban. What are the reasons one may switch between the agents and how is this done? Discussed in this article are the 4 agents approved in the United States, their characteristics, reasons one may switch, and methods for conversion. After a thorough search of original trial data and recent expert review articles, we have summarized the most recent recommendations below and briefly discuss upcoming oral anticoagulants that show promise.

Two blind persons received corneal transplants from a single donor who showed no signs of rabies before he died. One of the recipients, a young girl, died 16 days later of rabies and the other recipient survived. We discuss the possible mode of transmission of rabies to the first recipient and the management of the second recipient., (Copyright 2012, NMJI.)