tbuckley/cabot-search huggingface dataset:
FDG PET/CT in a Case of Human African Trypanosomiasis (Sleeping Sickness)
Authors: Zhengguang Xiao, Aisheng Dong, Yang Wang
Journal: Clinical Nuclear Medicine (2018)

Human African trypanosomiasis imported to nonendemic countries is rare. It is very difficult to establish the correct diagnosis of human African trypanosomiasis in nonendemic areas. We present a case of human African trypanosomiasis with MRI and FDG PET/CT findings. Head MRI showed hyperintense areas in bilateral internal capsules. Abdominal and pelvic MRI showed hepatosplenomegaly and multiple enlarged lymph nodes. FDG PET/CT showed generalized hypermetabolic lymph nodes, diffuse FDG uptake of the spleen, and hepatosplenomegaly mimicking lymphoma. In addition, FDG PET/CT revealed decreased FDG uptake in the medial occipital cortex and cardiomegaly with pericardial effusion.
At-risk children with asthma (ARC): a systematic review
Authors: Audrey Buelo, Susannah McLean, Steven Julious, Javier Flores-Kim, Andy Bush, John Henderson, James Y Paton, Aziz Sheikh, Michael Shields, Hilary Pinnock
Journal: Thorax (2018)

Introduction Asthma attacks are responsible for considerable morbidity and may be fatal. We aimed to identify and weight risk factors for asthma attacks in children (5–12 years) in order to inform and prioritise care. Methods We systematically searched six databases (May 2016; updated with forward citations January 2017) with no language/date restrictions. Two reviewers independently selected studies for inclusion, assessed study quality and extracted data. Heterogeneity precluded meta-analysis. Weighting was undertaken by an Expert Panel who independently assessed each variable for degree of risk and confidence in the assessment (based on study quality and size, effect sizes, biological plausibility and consistency of results) and then achieved consensus by discussion. Assessments were finally presented, discussed and agreed at a multidisciplinary workshop. Results From 16 109 records, we included 68 papers (28 cohort; 4 case-control; 36 cross-sectional studies). Previous asthma attacks were associated with greatly increased risk of attack (ORs between 2.0 and 4.1). Persistent symptoms (ORs between 1.4 and 7.8) and poor access to care (ORs between 1.2 and 2.3) were associated with moderately/greatly increased risk. A moderately increased risk was associated with suboptimal drug regimen, comorbid atopic/allergic disease, African-American ethnicity (USA), poverty and vitamin D deficiency. Environmental tobacco smoke exposure, younger age, obesity and low parental education were associated with slightly increased risk. Discussion Assessment of the clinical and demographic features identified in this review may help clinicians to focus risk reduction management on the high-risk child. Population level factors may be used by health service planners and policymakers to target healthcare initiatives. Trial registration number CRD42016037464.
Transcutaneously refillable, 3D-printed biopolymeric encapsulation system for the transplantation of endocrine cells
Authors: Marco Farina, Corrine Ying Xuan Chua, Andrea Ballerini, Usha Thekkedath, Jenolyn F. Alexander, Jessica R. Rhudy, Gianluca Torchio, Daniel Fraga, Ravi R. Pathak, Mariana Villanueva, Crystal S. Shin, Jean A. Niles, Raffaella Sesana, Danilo Demarchi, Andrew G. Sikora, Ghanashyam S. Acharya, A. Osama Gaber, Joan E. Nichols, Alessandro Grattoni
Journal: Biomaterials (2018)
Lipid metabolism reprogramming and its potential targets in cancer
Authors: Chunming Cheng, Feng Geng, Xiang Cheng, Deliang Guo
Journal: Cancer Communications (2018)

Abstract Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy. Increased lipid uptake, storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. Lipids constitute the basic structure of membranes and also function as signaling molecules and energy sources. Sterol regulatory element‐binding proteins (SREBPs), a family of membrane‐bound transcription factors in the endoplasmic reticulum, play a central role in the regulation of lipid metabolism. Recent studies have revealed that SREBPs are highly up‐regulated in various cancers and promote tumor growth. SREBP cleavage‐activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor, thus linking glucose metabolism and de novo lipid synthesis. Targeting altered lipid metabolic pathways has become a promising anti‐cancer strategy. This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy, and highlights potential molecular targets and their inhibitors for cancer treatment.
Treatment of Relapsed Myeloma in a Patient With Renal Insufficiency
Authors: Joan Bladé, Laura Rosiñol, María Teresa Cibeira, Carlos Fernández de Larrea
Journal: Journal of Clinical Oncology (2018)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old man was diagnosed in March 2010 with stage III immunoglobulin G kappa multiple myeloma (MM) after presenting with bone pain as a result of multiple lytic bone lesions and T12 vertebral collapse. Laboratory work-up showed a serum M protein of 72 g/L and a 24-hour kappa light-chain urine protein excretion of 730 mg, hemoglobin of 10.2 g/dL, serum albumin of 49 g/L, serum β 2 -microglobulin of 6.4 mg/L, serum creatinine level of 1.6 mg/dL with an estimated glomerular filtration rate (eGFR) of 47 mL/min/1.73 m 2 , and normal serum calcium and lactate dehydrogenase (LDH) levels. His bone marrow contained 58% plasma cells, which showed the 17p deletion abnormality (Fig 1). He was treated with vertebroplasty and alternating chemotherapy with carmustine, vincristine, cyclophosphamide, melphalan, and prednisone and vincristine, carmustine, doxorubicin and dexamethasone. Because of progressive disease, salvage therapy with bortezomib and dexamethasone was administered with no response. The patient was then switched to lenalidomide and dexamethasone, which yielded minimal response. He underwent autologous stem-cell transplantation (ASCT) with melphalan 200 mg/m 2 as high-dose therapy in February 2011, which led to a partial response, but in December 2011, progressive disease was documented, and the patient was enrolled in a clinical trial of carfilzomib monotherapy, with stable disease for 33 cycles. In October 2014 serum M protein rose to 38.6 g/L, with 24-hour kappa light-chain urine protein excretion of 840 mg, serum creatinine of 2.1 mg/dL, and an eGFR of 41 mL/min/1.73 m 2 . He presented to discuss ongoing treatment options.
Defining Survivorship Trajectories Across Patients With Solid Tumors
Authors: Robert L. Dood, Yang Zhao, Shannon D. Armbruster, Robert L. Coleman, Shelley Tworoger, Anil K. Sood, Keith A. Baggerly
Journal: JAMA Oncology (2018)

Survivorship involves a multidisciplinary approach to surveillance and management of comorbidities and secondary cancers, overseen by oncologists, surgeons, and primary care physicians. Optimal timing and coordination of care, however, is unclear and often based on arbitrary 5-year cutoffs.To determine high- and low-risk periods for all tumor types that could define when survivorship care might best be overseen by oncologists and when to transition to primary care physicians.In this pan-cancer, longitudinal, observational study, excess mortality hazard, calculated as an annualized mortality risk above a baseline population, was plotted over time. The time this hazard took to stabilize defined a high-risk period. The percent morality elevation above age- and sex-matched controls in the latter low-risk period was reported as a mortality gap. The US population-based Surveillance, Epidemiology, and End Results database defined the cancer population, and the US Census life tables defined controls. Incident cases of patients with cancer were separated into tumor types based on International Classification of Diseases for Oncology definitions.Population-level data on incident cancer cases was compared with the general US population.Overall mortality and cause of death were reported on observed cancer cases.A total of 2 317 185 patients (median age, 63 years; 49.8% female) with 66 primary tumor types were evaluated. High-risk surveillance period durations ranged from less than 1 year (breast, prostate, lip, ocular, and parathyroid cancers) up to 19 years (unspecified gastrointestinal cancers). The annualized mortality gap, representing the excess mortality in the stable period, ranged from a median 0.26% to 9.33% excess annual mortality (thyroid and hypopharyngeal cancer populations, respectively). Cluster analysis produced 6 risk cluster groups: group 1, with median survival of 16.2 (5th to 95th percentile range [PR], 10.7-40.2) years and median high-risk period of 2.5 (PR, 0-5.0) years; group 2, 8.3 (PR, 5.1-23.3) and 2.5 (PR, 4.0-8.0) years; group 3, 2.8 (PR, 1.4-3.7) and 7.0 (PR, 6.0-11.1) years; group 4, 1.6 (PR, 1.5-1.8) and 6.0 (PR, 5.1-11.4) years; group 5, 0.8 (PR, 0.5-1.2) and 0.8 (PR, 0.5-1.2) years; and group 6, 0.5 (PR, 0.4-0.8) and 12.0 (PR, 9.3-12.9) years, respectively. Subanalyses of selected tumor types in these groups revealed that stratifying on stage and histologic type can change the risk cluster and guidance for care.These findings indicate that a standardized 5-year surveillance period is inadequate for some cancers while excessive for others. High-risk cancers require the most resources with the longest high-risk period, highest persistent baseline mortality risk, and longest period of primary cancer mortality, all arguing for longer follow-up with an oncologist in these cancers.
Intraoperative radiation therapy (IORT) in early stage breast cancer: A first for Africa.
Authors: Yastira Ramdas, Lucienne Van Schalkwyk, Carol Benn
Journal: Journal of Clinical Oncology (2018)

e12592 Background: The shortage of radiotherapy services in low to middle income countries means that some patients requiring radiation may not receive it. The available radiotherapy units are overburdened, resulting in delays to therapy or the need to shorten the treatment course. This compromises the provision of breast conservation. IORT may offer an innovative solution to this. In November 2017, our unit became the first in Africa to offer IORT to early breast cancer patients. Methods: We performed a retrospective review of the first cases of IORT in a multidisciplinary unit in Johannesburg, South Africa from its initiation in November 2017. Patient selection criteria was mainly based on the current American Society of Radiation Oncology (ASTRO) guidelines. Most patients who received IORT for early stage disease had a negative upfront sentinel lymph node biopsy, negating the need for EBRT. Patient characteristics, histology, the use of oncoplastic surgery and any early complications were recorded Results: To date, 21 patients have received IORT. Nine patients elected to have IORT due to distance from a radiation centre, while the remainder selected IORT after being offered a choice between EBRT and IORT. The mean age of the patients was 61 years (range 44 - 84 years). Nine patients presented with left-sided tumours. The majority of the tumours were of ductal origin (n = 19) and of the luminal A biological subtype (n = 17), with a mean tumour size of 15mm. A single patient with locally advanced breast cancer (T4N2) opted for IORT as a boost in addition to planned EBRT. Fifteen patients underwent wide local excision with mastopexy, while the remainder underwent either wide local excision with parenchymal flap (n = 5) or locoregional flap (n = 1). Few complications were observed at 6 weeks follow-up: 2 patients presented with localised areas of fat necrosis and another with a seroma in the wound bed. Conclusions: The early IORT experience in Africa confirms viability, with a low complication rate and no detrimental effects on breast conservation. IORT has been well accepted by our patients. Local recurrence data will be published in due course. Medical insurance, education and cost models still need to be addressed in the African setting.
Multicenter phase II study of pembrolizumab (P) in advanced soft tissue (STS) and bone sarcomas (BS): Final results of SARC028 and biomarker analyses.
Authors: Melissa Amber Burgess, Vanessa Bolejack, Brian Andrew Van Tine, Scott Schuetze, James Hu, Sandra P. D'Angelo, Steven Attia, Dennis A. Priebat, Scott H. Okuno, Richard F. Riedel, Lara Emily Davis, Sujana Movva, Damon R. Reed, Lisa Helene Butterfield, Jason Roszik, Denise K. Reinke, Laurence H. Baker, Robert G. Maki, Shreyaskumar Patel, Hussein Abdul-Hassan Tawbi
Journal: Journal of Clinical Oncology (2017)

11008 Background: SARC028 is the first multicenter Phase II study of P monotherapy in patients (pts) with STS and BS. Designed to detect clinical efficacy signals in multiple histologies, the study collected blood &amp; tissue samples on all pts. We report extended clinical follow-up and in-depth biomarker correlates of response. Methods: The primary endpoint was objective response rate (ORR) by RECIST 1.1. Secondary endpoints were safety, 12 wk progression-free survival (PFS), and overall survival (OS). The STS arm had 10 pts in each of 4 cohorts: undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), synovial sarcoma (SS) and leiomyosarcoma (LMS). The BS arm included 40 pts with osteosarcoma (OS), Ewing sarcoma (ES) or dedifferentiated chondrosarcoma (CS). Pre- and on-P biopsies were required as well as blood at multiple time points. Tumor was assessed for PD-L1 expression (clone 22C3) and immune infiltrates by multi-color IHC (Vectra). Ongoing analyses include circulating cytokine and checkpoint levels and exome (DNA), transcriptome (RNA), and T-cell receptor (TCR) sequencing. Results: 86 pts were enrolled, 80 were evaluable for response. For STS, median follow-up was 14.5 months. The ORR in the overall STS cohort was 18% and the 12-wk PFS 55% [95% CI, 42-71]). Clinical activity was variable by histologic subtype with 40% ORR in UPS (1 CR and 3PR out of 10 evaluable pts), 2 PR/10 were seen in DDLPS, 1PR/10 in SS and 0/10 in LMS. For BS, median follow-up was 12.3 months (ORR 5%; 12-wk PFS 28% [95% CI, 14-41]), with 1PR/22 OS, 1PR/5 CS and 0/13 ES. 70 pre-P tissues were analyzed (11 excluded for insufficiency), with PD-L1+ in 3/70 (4%); all 3 were UPS. Of the 2 evaluable pts, 1 had CR and 1 PR. 2 OS were PD-L1+ on multi-color IHC, 1 had PR. All PD-L1+ samples had CD8+ T-cell infiltration. There were no post-P PD-L1+ samples. Conclusions: P has clinical activity in UPS and LPS, and expansion cohorts in those subtypes are planned. Pre-treatment PD-L1 expression was infrequent, but correlated with T-cell infiltration and response in UPS &amp; OS. Ongoing biomarker analyses that may guide combination strategies are ongoing and will be presented at the meeting. Clinical trial information: NCT02301039.
Abstract 13848: Anatomic and Hemodynamic Changes in Single Ventricle Patients 3-9 Months After Fontan to the Teenage Years: Insights From Cardiac Magnetic Resonance and Computational Fluid Dyanmics
Authors: Mark A Fogel, Esther Kim, Matthew Harris, Kevin Whitehead, Marc keller, Thomas Spray, J William Gaynor, Stephanie Fuller, Christopher Mascio, Susan Nicolson, Lisa Montenegro, Laura Diaz-Berenstein, phillip Trusty, Alan Wei, Michael Tree, Ajit Yoganathan
Journal: Circulation (2016)

Introduction: Little is known of baseline cardiac magnetic resonance (CMR) data in single ventricle (SV) pts immediately after Fontan. In addition, total cavopulmonary connection (TCPC) changes from this point to the teen years may shed some light regarding how to optimize clinical outcome. Hypothesis: Anatomic, hemodynamic and computational fluid dynamic (CFD) parameters are significantly altered as pts age. Methods: SV pts 3-9 months after Fontan and teens were studied with CMR. Anatomy, flows and CFD modeling were performed. Significance = P&lt;0.05. Results: 22 were 3-9 months after Fontan (age 3±1.1 yrs, 0.6±0.3 yrs after Fontan) &amp; 25 were teens (age 16±1.8 yrs, 14.1±2.2 yrs after Fontan). Although a higher indexed powerloss (iPL) in teens almost reached significance, Reynold’s number &amp; particle resident time (time a red blood cell remains in the TCPC) were greater in teens than younger pts (table). Superior vena cava (SVC) pulsatility index (PI) was greater in younger pts while inferior vena cava (IVC) PI was greater in teens, owing to the primary caval return changing from SVC to IVC as pts age (table). Both cardiac index &amp; caval return decreased in teens while hepatic flow distribution (HFD) became more evenly distributed in teens (table). The % TCPC stenosis at its narrowest point was greater in teens (42.8 %) than younger pts (20.9%), P=0.009. In teens, iPL (R=0.39) and % TCPC stenosis (R=0.62) correlated with time from Fontan (P&lt;0.39 for both). Conclusion: In teens, iPL correlated with time from Fontan. Significant increase in particle resident time &amp; Reynold’s number occur as SV pts age, with increased narrowing of the TCPC while HFD became more even. SVC PI is higher in younger pts while IVC PI is higher in teens. Cardiac index &amp; caval return both decrease as pts age. These data serve as baseline information in the immediate post-operative state and may be used to aid in designing improved Fontan reconstruction to optimize clinical outcome.
Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone
Authors: Emily E. Noble, Joel D. Hahn, Vaibhav R. Konanur, Ted M. Hsu, Stephen J. Page, Alyssa M. Cortella, Clarissa M. Liu, Monica Y. Song, Andrea N. Suarez, Caroline C. Szujewski, Danielle Rider, Jamie E. Clarke, Martin Darvas, Suzanne M. Appleyard, Scott E. Kanoski
Journal: Cell Metabolism (2018)
Clinical assessment of pancreatic cancer cases with thromboembolism complications.
Authors: Yusuke Nagata, Ryoichi Sawada, Tomohiro Kano, Utako Ishimoto, Takashi Nishimura, Masaaki Noguchi, Katsushi Amano, Tomohiro Kato, Masayuki Saruta
Journal: Journal of Clinical Oncology (2018)

495 Background: Cancer patients, particularly those with pancreatic cancer (PC), have an increased risk of developing thromboembolism, such as venous thromboembolism (VTE) and cerebral infarction (CI). Moreover, thromboembolisms in cancer are associated with poor prognosis. The purpose of this study was to investigate the clinical characteristics, clinical courses, and prognosis of PC patients (pts) with VTE and/or CI. Methods: We retrospectively reviewed the medical records of PC pts who were radiologically diagnosed with VTE and/or CI at our institution. We investigated the patients’ clinical information and evaluated overall survival (OS), which was defined as the date from diagnosis of VTE and/or CI to the date of death by any causes or censored. Results: Between January 2012 and December 2015, 100 pts were diagnosed with PC. A total of 14 pts developed VTE and/or CI at our institution. All 14 pts had unresectable advanced or metastatic PC, 10 pts (71%) were men, and the median age at the time of VTE and/or CI diagnosis was 68.8 (range, 29–84) years. Complications of VTE and CI developed in 6 (43%) and 8 pts (57%), respectively (3 pts with development of both VTE and CI were included as CI). The median OS in pts who developed VTE and CI was 7.59 and 1.48 months (p = 0.007), respectively. After the development of VTE and/or CI, 5 pts (36%) (3 with VTE and 2 with CI) received chemotherapy (CTx), while the remaining 9 pts (64%) received best supportive care (BSC). In pts with VTE, the median OS of those who received CTx and BSC was 7.59 and 3.15 months (p = 0.221), respectively. Meanwhile, in pts with CI, the median OS of those who received CTx and BSC was 3.84 and 1.48 months (p = 0.113), respectively. Conclusions: The prognosis of PC pts who developed CI as complications was significantly poorer than those who developed VTE. However, in both cases, treatment with CTx prolonged the OS of these patients.
Polymorphisms of MTHFR and TYMS to predict capecitabine-induced hand-foot syndrome in patients with metastatic breast cancer.
Authors: Shaoyan Lin, Binghe Xu, Jian Yue, Xiuwen Guan, Xuefeng Xia
Journal: Journal of Clinical Oncology (2018)

1085 Background: Breast cancer is a global problem, and 1.7 million new cases are diagnosed per year. Capecitabine, an oral prodrug of fluorouracil, has been reported to be effective in patients with metastatic breast cancer (MBC) and approved by the Unites States Food and Drug Administration for treatment of MBC. Hand-foot syndrome (HFS) is one of the most relevant dose-limiting adverse effects of capecitabine. If HFS is not handled well, it can deteriorate rapidly and lead to the treatment interruptions which may influence on the treatment efficacy. Methods: In our study, we investigated the association between single nucleotide polymorphism (SNP) and capecitabine-based HFS in patients with MBC in Chinese Han population, in an attempt to identify some predictive genetic biomarkers. We selected 3 genes involved in capecitabine metabolism and screened genetic variants in the target genes. We genotyped a total of 22 SNPs in the thymidylate synthase gene (TYMS), the methylene tetrahydrofolate reductase gene (MTHFR) and the ribonucleotide reductase M1 gene (RRM1) in 342 patients treated with capecitabine-based chemotherapy. Results: Logistic regression analyses showed that genotype AG of rs3737964 [odds ratio (OR) = 0.54,95% confidence interval (CI) = 0.31-0.97, P = 0.038] and genotype AG of rs4846048 (OR = 0.54,95%CI = 0.30-0.98,P = 0.042) in MTHFR were protective factors for HFS. That was to say, patients with these two kinds of genotypes in the Chinese Han population might have 0.54-fold lower risk of suffering from HFS. Genotype GT of rs2606241 (OR = 1.27,95%CI = 0.73-2.23,P = 0.012) and genotype CT of rs2853741 (OR = 2.25,95%CI = 1.31-3.87,P = 0.012) in TYMS increased the incidence of HFS. Patients with genotype GT of rs2606241 and genotype CT of rs2853741 were found to have 1.27-fold and 2.25-fold higher risk of suffering from HFS. Conclusions: In summary, we have identified a panel of clinically useful pharmacogenetic markers predicting capecitabine-induced HFS in MBC patients.
GiniClust2: a cluster-aware, weighted ensemble clustering method for cell-type detection
Authors: Daphne Tsoucas, Guo-Cheng Yuan
Journal: Genome biology (2018)

Single-cell analysis is a powerful tool for dissecting the cellular composition within a tissue or organ. However, it remains difficult to detect rare and common cell types at the same time. Here, we present a new computational method, GiniClust2, to overcome this challenge. GiniClust2 combines the strengths of two complementary approaches, using the Gini index and Fano factor, respectively, through a cluster-aware, weighted ensemble clustering technique. GiniClust2 successfully identifies both common and rare cell types in diverse datasets, outperforming existing methods. GiniClust2 is scalable to large datasets.