tbuckley/cabot-search huggingface dataset:
Circulating tumor DNA (ctDNA) to detect neuroendocrine prostate cancer genomic and DNA methylation changes.
Authors: Himisha Beltran, Alessandro Romanel, Vincenza Conteduca, Nicola Casiraghi, Michael Sigouros, Gian Marco Franceschini, Tarcisio Fedrizzi, sheng-Yu Ku, Alicia Alonso, Juan Miguel Mosquera, Emma Dann, Andrea Sboner, Jenny Xiang, Olivier Elemento, David M. Nanus, Scott T. Tagawa, Matteo Benelli, Francesca Demichelis
Journal: Journal of Clinical Oncology (2020)

8 Background: Loss of androgen receptor signaling dependence occurs in approximately 20% of treatment resistant prostate cancers, and this may manifest as transformation to castration resistant neuroendocrine prostate cancer (CRPC-NE). The diagnosis of CRPC-NE relies on a metastatic tumor biopsy, which is invasive for patients. Here we study ctDNA as an approach to identify CRPC-NE-associated genomic and epigenomic changes. We also use this as a tool to understand tumor heterogeneity and clonal dynamics that occurs during CRPC-NE progression. Methods: 64 patients with metastatic prostate cancer (10 hormone naive, 35 castration resistant adenocarcinoma (CRPC-Adeno), 17 CRPC-NE) were prospectively enrolled for matched metastatic biopsy and blood collection. Twenty-four had multiple time-points, for total of 69 plasma and 98 metastatic tissues. Whole exome sequencing (WES) and whole genome bisulfite sequencing(of subset) of ctDNA,germline DNA, and metastatic biopsies were performed. Results: Overall there was high concordance of alterations between ctDNA and patient-matched metastasis, though this was highest in CRPC-NE. There was also less heterogeneity across patients with CRPC-NE. Alteration frequencies were consistent with published tissue-based studies with AR alterations enriched in CRPC-Adeno and TP53and RB1loss enriched in CRPC-NE ctDNA. The prognostic significance of these alterations differed based on histologic subtype. Allele-specific copy number analysis and serial sampling allowed for the detection and tracking of clonal and subclonal tumor cell populations. cfDNA methylation was reflective of methylation patterns in biopsies and detected CRPC-NE-associated epigenetic changes.A targeted set combining genomic ( TP53, RB1, CYLD, AR) and epigenomic(20 differential DNA methylation sites) was capable of identifying patients with CRPC-NE. Conclusions: WES and whole genome methylation of ctDNA is feasible, concordant with biopsy tissues, and identifies the spectrum and frequency of CRPC-NE genomic and epigenomic changes. A targeted panel extended and validated in larger cohorts could potentially improve the detection of CRPC-NE using non-invasive ctDNA profiling.
Skin TEWL results show significant improvements with Trilipid emollient compared to controls in infants and young children
Authors: Kari Nadeau, Sayantani Sindher, Evgeny Berdyshev, Melanie Shojinaga, Shifaa Alkotob, Sarah Alonzi, Sara Varadharajulu, Sharad Chandra, Sharon Chinthrajah, Helen Brough, Susan Chan, Gideon Lack, Donald Leung
Journal: Journal of Allergy and Clinical Immunology (2020)
Seasonal Patterns of Adherence of Air Purifier Use In Inner-City Children With Asthma
Authors: Parisa Kaviany, Joseph Collaco, Kirsten Koehler, Megan Wood, John Woo, Rachelle Koehl, Emily Brigham, Nadia Hansel, Meredith McCormack
Journal: Journal of Allergy and Clinical Immunology (2020)
Assessment of the Contribution of Endotoxin in the Pro-inflammatory Potential of Indoor Settled-Dust from Homes Water-Damaged During Hurricane Maria in San Juan, Puerto Rico
Authors: Tanha Rahman, Summer Pellechio, Hayat Srour, Ruslan Fomenko, Benjamin Bolanos, Filipa Godoy-Vitorino, Juan Maestre, Kerry Kinney, Humberto Cavallin
Journal: Journal of Allergy and Clinical Immunology (2020)
Serum microRNA-371a-3p levels to predict viable germ cell tumor in chemotherapy-naïve patients undergoing retroperitoneal lymph node dissection.
Authors: Nirmish Singla, John T. Lafin, Solomon L. Woldu, Yair Lotan, Cheryl Lewis, Kuntal Majmudar, Anna Savalyeva, Alexander P. Kenigsberg, Payal Kapur, Vitaly Margulis, Douglas Strand, Matthew Murray, James F. Amatruda, Aditya Bagrodia
Journal: Journal of Clinical Oncology (2020)

417 Background: Serum microRNAs are candidate biomarkers for diagnosing and monitoring germ cell tumors (GCTs). The ability of miRNA to inform treatment in low-stage chemotherapy-naïve patients is unexplored. We sought to evaluate the performance characteristics of serum miRNA levels to predict viable GCT in chemotherapy-naïve patients undergoing primary retroperitoneal lymph node dissection (RPLND). Methods: We prospectively collected presurgical serum samples and clinicopathologic characteristics from consecutive chemotherapy-naïve GCT patients undergoing primary RPLND from 2016-2019. Serum miRNAs (-367-3p/-371a-3p/-372-3p/-373-3p/-375) were isolated and quantified. RPLND histopathology was categorized as benign, viable GCT, or teratoma; miRNA levels were compared among groups. Performance characteristics, including receiver operating characteristic (ROC) curves, assessed the discriminative ability of each miRNA signature to predict viable GCT. Results: 24 patients with stage I-II GCT underwent RPLND, revealing viable GCT in 11 (46%), teratoma in 3 (13%), and benign pathology in 10 (42%) patients. miR-371a-3p was the most discriminatory serum miRNA for viable GCT, exhibiting ~13,000-fold increase in expression over teratoma or benign pathology. On ROC analysis, miR-371a-3p had AUC = 0.965, with sensitivity and specificity of 100% and 92%, respectively. The AUC for other serum miRNAs in predicting viable GCT were 0.874 (miR-367-3p), 0.846 (miR-372-3p), and 0.720 (miR-373-3p). These serum miRNAs were not predictive of pure teratoma. Potential limitations include small cohort size and no post-RPLND sera for comparison. Conclusions: Serum miRNAs, particularly miR-371a-3p, can accurately differentiate small-volume viable GCT from benign processes or teratoma in patients with negative serum tumor markers undergoing primary RPLND. If validated, these data suggest a basis to implement precision medicine strategies in treating patients with early-stage GCT.
Unmeasured Confounding in Observational Studies of Management of Cerebellar Intracranial Hemorrhage—Reply
Authors: Joji B. Kuramatsu, Kevin N. Sheth, Hagen B. Huttner
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Comparison of the safety and efficacy of single-stage endoscopic retrograde cholangiopancreatography plus laparoscopic cholecystectomy versus two-stage ERCP followed by laparoscopic cholecystectomy six-to-eight weeks later: A randomized controlled trial
Authors: Bahtiyar Muhammedoğlu, Ilhami Taner Kale
Journal: International Journal of Surgery (2020)
Creating new guidelines on how best to treat foot symptoms in people with EB
Authors: M.T. Khan, M. O'Sullivan, B. Faitli, J.E. Mellerio, R. Fawkes, M. Wood, L.D. Hubbard, A.G. Harris, L. Iacobaccio, T. Vlahovic, L. James, L. Brains, M. Fitzpatrick, K. Mayre‐Chilton
Journal: British Journal of Dermatology (2020)

Epidermolysis bullosa (EB) is a complex rare condition that affects the skin and many parts of the body. Those born with EB have skin so fragile they are called ‘butterfly children’, their skin is quite simply as fragile as the wing of a butterfly. In the UK it is estimated that there are more than 5,000 people living with EB and 500,000 worldwide. Little clinical guidance for care existed until DEBRA International started a programme to develop clinical practice guidelines (CPGs). There were no previous guidelines and few published studies on foot care in EB so treatment decisions were largely based on individual opinion and experience. The panel – made up of clinical experts and people living with EB representing Australia, the UK, and the USA – aimed to describe foot problems in people of all ages with EB, and summarise current evidence and management. The authors used a logical podiatric (foot) care literature review focussed on patients with EB. The authors found that the evidence in this area was limited but several interventions (treatments) currently practised by podiatrists show positive outcomes. The study allowed the group to make recommendations on how to treat foot and nail disorders in patients with EB. Furthermore, the authors concluded that further research is needed. This is a summary of the study: Foot care in epidermolysis bullosa: evidence-based guideline
Targeting metabolic dysregulation of T cells in kidney cancer.
Authors: Katy Beckermann, Kirsten Young, Rachel Hongo, Xiang Ye, Diana Contreras, Sierra Barone, Caroline E. Roe, Christof C. Smith, Benjamin Garrett Vincent, Jonathan M. Irish, Wendy Kimryn Rathmell, Jeffrey C. Rathmell
Journal: Journal of Clinical Oncology (2020)

722 Background: Cancer cells can inhibit effector T cells through both immunomodulatory receptors and alteration of the tumor microenvironment. Rather than efficient use of aerobic glycolysis by activated effector T cells, Renal Cell Carcinoma (RCC) infiltrating T cells (TIL) fail to increase glucose metabolism, and instead display increased reactive oxygen species (ROS) and mitochondrial dysfunction. CD8 RCC TIL also have notable differences in mitochondrial morphology compared to healthy control CD8 T cells and were punctate and dispersed rather than fused in networks. Here we test if RCC TIL can be re-activated and identify metabolic requirements for inflammatory TIL function. Methods: De-identified samples from tumor or adjacent normal tissue donations from patients with RCC were collected under an approved IRB protocol and processed into single cell suspensions of tumor and associated cells by mechanical dissociation to test TIL activation and metabolic requirements upon in vitro re-stimulation. Results: RNA-seq data suggested that CD8 from TIL rely on distinct metabolic pathways compared to control. While control T cells increased effector cytokine production and glycolysis with antigen receptor alone and further augmented this pathway with co-stimulation, single cell RNAseq showed that CD8 RCC TIL required co-stimulation for this transition. Co-stimulation can promote T cell glycolysis and we found antigen receptor stimulation with CD28-mediated co-stimulation increased function of CD8 RCC TIL as indicated by increased surface markers of activation and IFNγproduction. This was accompanied by rescue of metabolic markers, including increased mitochondrial mass and markers of electron transport. Improved functional capacity was dependent upon glycolysis because inhibition with 2-deoxyglucose limited CD8 RCC TIL activation following CD28 co-stimulation. Conclusions: Bypassing metabolic defects restore markers of TIL activation and effector function.These datademonstrate that CD8 RCC TIL can be functionally restored but that this requires the ability to increase glucose metabolism. These findings may allow for combined therapies to improve response rates of checkpoint inhibition in this disease.
Mucoadhesive-to-penetrating controllable peptosomes-in-microspheres co-loaded with anti-miR-31 oligonucleotide and Curcumin for targeted colorectal cancer therapy
Authors: Ran Zhao, Sujuan Du, Ying Liu, Cong Lv, Yongli Song, Xinchun Chen, Bing Zhang, Dan Li, Shan Gao, Wei Cui, Maksim V. Plikus, Xiaohua Hou, Kaichun Wu, Zhanju Liu, Zhihua Liu, Yingzi Cong, Yuan Li, Zhengquan Yu
Journal: Theranostics (2020)

Background: Accumulating evidences indicate that nanomedicines greatly decrease the side effects and enhance the efficacy of colorectal cancer (CRC) treatment. In particular, the use of rectal delivery of nanomedicines, with advantages such as fast therapeutic effects and a diminishing hepatic first-pass effect, is currently emerging. Method: We established a CRC targeted delivery system, in which α-lactalbumin peptosomes (PSs) co-loaded with a microRNA (miR)-31 inhibitor (miR-31i) and curcumin (Cur) were encapsuslated in thiolated TEMPO oxidized Konjac glucomannan (sOKGM) microspheres, referred as sOKGM-PS-miR-31i/Cur. The CRC targeting capability, drug release profiles, mucoadhesive-to-penetrating properties and therapeutic efficacy of sOKGM-PS-miR-31i/Cur delivery system were evaluated in colorectal cancer cells and azoxymethane-dextran sodium (AOM-DSS) induced tumor models. Results: sOKGM-PS-miR-31i/Cur delivery system were stable in the harsh gastrointestinal environment after rectal or oral administration; and were also mucoadhesive due to disulfide bond interactions with the colonic mucus layer, resulting in an enhanced drug retention and local bioavailability in the colon. Concomitantly, the released PS-miR-31i/Cur PSs from the microsphere was mucus-penetrating, efficiently passing through the colonic mucus layer, and allowed Cur and miR-31i specifically target to colon tumor cells with the guide of CD133 targeting peptides. Consequently, rectal delivery of sOKGM-PS-miR-31i/Cur microspheres suppressed tumor growth in an azoxymethane-dextran sodium sulfate (AOM-DSS)-induced tumor model. Conclusion: sOKGM-PS-miR-31i/Cur microspheres are effective rectal delivery system with combined advantages of mucoadhesive and mucus-penetrating properties, representing a potent and viable therapeutic approach for CRC.
Single-Cell Reconstruction of Progression Trajectory Reveals Intervention Principles in Pathological Cardiac Hypertrophy
Authors: Zongna Ren, Peng Yu, Dandan Li, Zheng Li, Yingnan Liao, Yin Wang, Bingying Zhou, Li Wang
Journal: Circulation (2020)

Pressure overload-induced pathological cardiac hypertrophy is a common predecessor of heart failure, the latter of which remains a major cardiovascular disease with increasing incidence and mortality worldwide. Current therapeutics typically involve partially relieving the heart's workload after the onset of heart failure. Thus, more pathogenesis-, stage-, and cell type-specific treatment strategies require refined dissection of the entire progression at the cellular and molecular levels.By analyzing the transcriptomes of 11,492 single cells and identifying major cell types, including both cardiomyocytes and noncardiomyocytes, on the basis of their molecular signatures, at different stages during the progression of pressure overload-induced cardiac hypertrophy in a mouse model, we characterized the spatiotemporal interplay among cell types, and tested potential pharmacological treatment strategies to retard its progression in vivo.We illustrated the dynamics of all major cardiac cell types, including cardiomyocytes, endothelial cells, fibroblasts, and macrophages, as well as those of their respective subtypes, during the progression of disease. Cellular crosstalk analysis revealed stagewise utilization of specific noncardiomyocytes during the deterioration of heart function. Specifically, macrophage activation and subtype switching, a key event at middle-stage of cardiac hypertrophy, was successfully targeted by Dapagliflozin, a sodium glucose cotransporter 2 inhibitor, in clinical trials for patients with heart failure, as well as TD139 and Arglabin, two anti-inflammatory agents new to cardiac diseases, to preserve cardiac function and attenuate fibrosis. Similar molecular patterns of hypertrophy were also observed in human patient samples of hypertrophic cardiomyopathy and heart failure.Together, our study not only illustrated dynamically changing cell type crosstalk during pathological cardiac hypertrophy but also shed light on strategies for cell type- and stage-specific intervention in cardiac diseases.
Association of moderate alcohol intake with in vivo amyloid-beta deposition in human brain: A cross-sectional study
Authors: Jee Wook Kim, Min Soo Byun, Dahyun Yi, Jun Ho Lee, Kang Ko, So Yeon Jeon, Bo Kyung Sohn, Jun-Young Lee, Yu Kyeong Kim, Seong A Shin, Chul-Ho Sohn, Dong Young Lee
Journal: PLoS Medicine (2020)

Background An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aβ) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aβ deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain. Methods and findings The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1–13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1–13 SDs/week) was significantly associated with a lower Aβ positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163–0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history. Conclusions In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aβ deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury.
Transcription-Associated Cyclin-Dependent Kinases as Targets and Biomarkers for Cancer Therapy
Authors: Jonathan Chou, David A. Quigley, Troy M. Robinson, Felix Y. Feng, Alan Ashworth
Journal: Cancer Discovery (2020)

Drugs targeting the cell cycle-regulatory cyclin-dependent kinase (CDK) 4 and 6 have been approved for the treatment of hormone receptor-positive breast cancer, and inhibitors targeting other cell-cycle CDKs are currently in clinical trials. Another class of CDKs, the transcription-associated CDKs, including CDK7, CDK8, CDK9, CDK12 and CDK13, are critical regulators of gene expression. Recent evidence suggests several novel functions of these CDKs, including regulation of epigenetic modifications, intronic polyadenylation, DNA-damage responses, and genomic stability. Here, we summarize our current understanding of the transcriptional CDKs, their utility as biomarkers, and their potential as therapeutic targets. SIGNIFICANCE: CDK inhibitors targeting CDK4 and CDK6 have been approved in hormone receptor-positive breast cancer, and inhibitors targeting other cell-cycle CDKs are currently in clinical trials. Several studies now point to potential therapeutic opportunities by inhibiting the transcription-associated CDKs as well as therapeutic vulnerabilities with PARP inhibitors and immunotherapy in tumors deficient in these CDKs.
Impact of initial treatment selection on clinical outcomes after biochemical failure in radiorecurrent high-risk prostate cancer.
Authors: Rebecca Levin-Epstein, Tahmineh Romero, Jessica Karen Wong, Kiri Cook, Robert Timothy Dess, Daniel Eidelberg Spratt, Brian Joseph Moran, Gregory Stephen Merrick, Phuoc T. Tran, David Jeffrey Demanes, Brad J. Stish, Daniel J. Krauss, Trude Baastad Wedde, Wolfgang Lilleby, Richard Stock, Jonathan David Tward, Michael L. Steinberg, Eric M. Horwitz, Rahul D. Tendulkar, Amar Upadhyaya Kishan
Journal: Journal of Clinical Oncology (2020)

208 Background: Treatment of high risk prostate cancer (HRPCa) with external beam radiotherapy (EBRT) plus brachytherapy (BT) boost (EBRT+BT) has been prospectively associated with lower rates of BCR, albeit potentially with increased toxicity, and retrospectively linked to decreased distant metastasis (DM) and PCa-specific mortality (PCSM) compared to EBRT alone. However, it is unclear whether patients who develop BCR following either approach have similar downstream oncologic outcomes. Methods: We identified 706 out of 3820 men with HRPCa treated at 13 institutions from 1998-2015 with EBRT (n=468/2134) or EBRT+BT (n=238/1686) who developed BCR. We compared rates of DM, PCSM, and all-cause mortality (ACM) after BCR between treatment groups using Fine-Gray competing risk regression. Models were adjusted for age, Gleason grade group, initial PSA (iPSA), clinical T stage, time-dependent use of systemic salvage, and interval to BCR using inverse probability of treatment weighting. Results: Median follow-up was 9.9 years from RT and 4.8 years from BCR. Groups were similar in age, iPSA, presence of ≥2 HR features, and median interval to BCR (3.3 years). Most men received neoadjuvant/concurrent androgen deprivation therapy (ADT), 92.5% and 91.0% for EBRT and EBRT+BT, respectively, though for a longer duration with EBRT (median 14.7 vs. 9.0 months, p=0.0012). Local and systemic salvage rates were 2.3% and 36.3% after EBRT, and 2.6% and 43.6% after EBRT+BT, respectively. Initial EBRT+BT was associated with significantly lower rates of DM after BCR (HR 0.48, 95% CI 0.36-0.64, p&lt;0.001). Rates of PCSM and ACM did not significantly differ (HR 0.93, 95% CI 0.67-1.30, p=0.93, and HR 0.8, 95% CI 0.6-1.1, p=0.11, respectively). Conclusions: In this large retrospective series of radiorecurrent HRPCa, initial treatment with EBRT+BT was associated with significantly lower rates of DM after BCR compared with EBRT, despite shorter ADT use and a similar median interval to BCR. Local salvage was widely underutilized in both groups. In the absence of salvage for local failure after EBRT, upfront treatment intensification with BT may reduce DM, though not PCSM or ACM, even after development of BCR.