tbuckley/cabot-search huggingface dataset:
Adenocarcinoma of the Lung With Initial Presentation as Painful Testicular Metastasis
Authors: Punit Sharma
Journal: Clinical Nuclear Medicine (2020)

Testicular metastasis is rare, with prostate cancer followed by lung cancer being the commonest primary site. Usually these are incidentally detected and are rarely symptomatic. We present an unusual case of adenocarcinoma lung, presenting initially with right testicular pain. Further workup with 18F-FDG PET/CT demonstrated primary malignancy of the left lung with nodal and right testicular metastasis.
DNA Methylation of Cannabinoid Receptor Interacting Protein 1 Promotes Pathogenesis of Intrahepatic Cholangiocarcinoma Through Suppressing Parkin‐Dependent Pyruvate Kinase M2 Ubiquitination
Authors: Diyu Chen, Hao Wu, Xiaode Feng, Yunhao Chen, Zhen Lv, Vishnu Goutham Kota, Junru Chen, Wenxuan Wu, Yuejie Lu, Hua Liu, Yanpeng Zhang, Shusen Zheng, Jian Wu
Journal: Hepatology (2020)

Methylation landscape is important for maintaining the silence of cannabinoid receptor-interacting protein 1 (CNRIP1) in some tumors. However, the role of CNRIP1 in intrahepatic cholangiocarcinoma (ICC) remains poorly defined.In our study, we showed that CNRIP1 was down-regulated in ICC tissues, and low expression of CNRIP1 was significantly associated with poor prognosis of patients with ICC in 3-year overall survival and tumor-free survival. Investigating the genomic DNA methylation profile, we disclosed a CpG island site named CNRIP1 MS-2 (CNRIP1 methylation site-2) that contributes to the down-regulation of CNRIP1. In addition, the methylation level of CNRIP1 MS-2 was correlated to the pathological grade, metastasis, and tumor-node-metastasis classification in ICC. Notably, we observed that CNRIP1 suppressed tumor cell migration, invasion, and proliferation by inhibiting the activity of pyruvate kinase M2 (PKM2). Sustained overexpression of CNRIP1 suppressed the in vivo tumor growth in a mouse xenograft model. It was also found that CNRIP1 overexpression activated Parkin (an E3 ubiquitin ligase), which resulted in the protein degradation of PKM2 in ICC cells.We identified that CNRIP1 acted as a putative tumor suppressor in ICC, which suggested that CNRIP1 could be a candidate biomarker for predicting tumor recurrence in patients with ICC. Furthermore, these findings highlight a potential therapeutic approach in targeting the CNRIP1/Parkin/PKM2 pathway for the treatment of ICC.
<i>Capnocytophaga canimorsus</i> Infection
Authors: Robert D H Markewitz, Tobias Graf
Journal: New England Journal of Medicine (2020)

A 62-year-old man presented to the ED with a 1-day history of fever that occurred 4 days after a dog bite. Peripheral-blood smear showed the presence of both intracellular and extracellular bacteria, and blood cultures grew C. canimorsus.
National burden estimates of hospitalisations for acute lower respiratory infections due to respiratory syncytial virus in young children in 2019 among 58 countries: a modelling study
Authors: You Li, Emily K Johnson, Ting Shi, Harry Campbell, Sandra S Chaves, Catherine Commaille-Chapus, Izzie Dighero, Spencer L James, Cédric Mahé, Yujing Ooi, John Paget, Tayma van Pomeren, Cécile Viboud, Harish Nair
Journal: The Lancet Respiratory Medicine (2020)
Arsenic Exposure and Glucose Metabolism: Experimental Studies Suggest Implications for Type 2 Diabetes
Authors: Lindsey Konkel
Journal: Environmental Health Perspectives (2020)

This micrograph of a pancreatic b cell shows insulin granules in blue, mitochondria in green, and the nucleus in purple.Disruption of b cell function is one of several potential mechanisms that could explain the association between arsenic exposure and type 2 diabetes.
Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial
Authors: Elizabeth A Mittendorf, Hong Zhang, Carlos H Barrios, Shigehira Saji, Kyung Hae Jung, Roberto Hegg, Andreas Koehler, Joohyuk Sohn, Hiroji Iwata, Melinda L Telli, Cristiano Ferrario, Kevin Punie, Frédérique Penault-Llorca, Shilpen Patel, Anh Nguyen Duc, Mario Liste-Hermoso, Vidya Maiya, Luciana Molinero, Stephen Y Chui, Nadia Harbeck
Journal: The Lancet (2020)
Changes in Management of Type 2 Diabetes Before and After Severe Hypoglycemia
Authors: Pavithra Vijayakumar, Shuling Liu, Rozalina G. McCoy, Andrew J. Karter, Kasia J. Lipska
Journal: Diabetes Care (2020)

Severe hypoglycemia in patients with diabetes is an adverse drug event that is associated with poor outcomes, such as cardiovascular events, falls, high rehospitalization rates, and increased mortality (1,2). Several strategies, including adjustment of glucose-lowering therapy and glycemic targets, have been recommended in patients with severe hypoglycemia (1,3). However, it is not clear how changes in diabetes management are maintained after severe hypoglycemia among patients with type 2 diabetes.

We conducted a retrospective analysis of data from the OptumLabs Data Warehouse, a de-identified administrative claims database of over 200 million individuals enrolled in commercial and Medicare Advantage plans across the U.S. (4). Data were accessed in adherence with the Health Insurance Portability and Accountability Act of 1996, and the Yale School of Medicine Human Investigations Committee deemed the study exempt from institutional review board review.

We included commercially insured or Medicare Advantage beneficiaries who were aged 18 years or older, had pharmacologically treated type 2 diabetes, and had a severe hypoglycemic event. Severe hypoglycemia was identified as the first event during an observation window of 1 July 2013 through 30 June 2014, based on primary/principal diagnosis codes for hypoglycemia from an emergency department visit, observation stay, or hospital …
A novel probiotic therapeutic in a murine model of <i>Clostridioides difficile</i> colitis
Authors: Rita D. Shelby, Grace E. Janzow, Lauren Mashburn-Warren, Jeffrey Galley, Natalie Tengberg, Jason Navarro, Miriam Conces, Michael T. Bailey, Steven D. Goodman, Gail E. Besner
Journal: Gut Microbes (2020)

For prophylactic therapy, mice received an oral antibiotic cocktail followed by clindamycin injection, followed by probiotic administration (planktonic vs. biofilm state), followed by C. difficile oral gavage. For treatment therapy, mice received antibiotics and C. difficile first, followed by probiotic administration. Clinical sickness scores (CSS) and intestinal histologic injury scores (HIS) were assigned.In the Prophylactic Therapy model, CSS: 67% of untreated mice exposed to C. difficile demonstrated CSS ≥ 6, which is consistent with C. difficile infection (p< .001 compared to unexposed mice). In mice treated with planktonic Lr, 55% had a CSS ≥ 6, but only 19% of mice treated with Lr in its biofilm state had CSS ≥ 6 (p< .001). Mice receiving Lr + DM-Maltose lost the least amount of weight compared to mice receiving saline (p = .004676) or to mice receiving Lr (p= .003185). HIS: 77% of untreated mice exposed to C. difficile had HIS scores ≥4, which is consistent with C. difficile infection. In mice treated with planktonic Lr, 62% had HIS ≥4, but only 19% of mice treated with Lr in its biofilm state had HIS ≥4. (p< .001). Additionally, mice treated with Lr in its biofilm state had better survival compared to untreated mice and to mice treated with planktonic Lr (p ≤ 0.05). Similar findings for weight loss, CSS, HIS and survival were obtained for Treatment Therapy.A single dose of Lactobacillus reuteri in its biofilm state reduces the severity and incidence of experimental C. difficile infection when administered as both prophylactic and treatment therapy.
Molecular response after obinutuzumab plus high-dose cytarabine induction for transplant-eligible patients with untreated mantle cell lymphoma (LyMa-101): a phase 2 trial of the LYSA group
Authors: Steven Le Gouill, Asma Beldi-Ferchiou, Marion Alcantara, Victoria Cacheux, Violaine Safar, Barbara Burroni, Stéphanie Guidez, Thomas Gastinne, Danielle Canioni, Catherine Thieblemont, Hervé Maisonneuve, Caroline Bodet-Milin, Roch Houot, Lucie Oberic, Krimo Bouabdallah, Charles Bescond, Ghandi Damaj, Arnaud Jaccard, Nicolas Daguindau, Anne Moreau, Hervé Tilly, Vincent Ribrag, Marie-Hélène Delfau-Larue, Olivier Hermine, Elizabeth Macintyre
Journal: The Lancet Haematology (2020)
Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial
Authors: Alexander M. M. Eggermont, Christian U. Blank, Mario Mandala, Georgina V. Long, Victoria G. Atkinson, Stéphane Dalle, Andrew M. Haydon, Andrey Meshcheryakov, Adnan Khattak, Matteo S. Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A. Ascierto, Piotr Rutkowski, Dirk Schadendorf, Rutger Koornstra, Leonel Hernandez-Aya, Anna Maria Di Giacomo, Alfonsus J. M. van den Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Paul C. Lorigan, Alexander C. J. van Akkooi, Clemens Krepler, Nageatte Ibrahim, Sandrine Marreaud, Michal Kicinski, Stefan Suciu, Caroline Robert
Journal: Journal of Clinical Oncology (2020)

We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up.A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)-positive tumors.Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1-positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/Kv wild type).In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.
Bacteria‐Derived Nanoparticles: Multifunctional Containers for Diagnostic and Therapeutic Applications
Authors: Lin Liu, Jiahe Wu, Jianqing Gao, Xiaoyang Lu
Journal: Advanced Healthcare Materials (2020)

Abstract In recent decades, investigations on bacteria‐derived materials have progressed from being a proof of concept to a means for improving traditional biomaterials. Owing to their unique characteristics, such as gene manipulation, rapid proliferation, and specific targeting, bacteria‐derived materials have provided remarkable flexibility in applied biomedical functionalization. In this review, bacteria‐derived nanoparticles are focused on as a promising biomaterial, introducing several bacterial species with great potential and useful strategies for fabrication. Through well‐designed choices, bacteria‐derived nanoparticles can be exploited to obtain functional bacteria‐mimicking materials for a variety of applications, including cargo delivery, imaging, therapy, and immune modulation. Finally, the prospects and challenges of bacteria‐derived nanoparticles are discussed. Particularly, safety concerns regarding the use of bacteria and their immunogenicity remain major obstacles to the clinical application of bacteria‐derived nanoparticles and these concerns are immediate priorities for the research community.
Host–Endosymbiont Genome Integration in a Deep-Sea Chemosymbiotic Clam
Authors: Jack Chi-Ho Ip, Ting Xu, Jin Sun, Runsheng Li, Chong Chen, Yi Lan, Zhuang Han, Haibin Zhang, Jiangong Wei, Hongbin Wang, Jun Tao, Zongwei Cai, Pei-Yuan Qian, Jian-Wen Qiu
Journal: Molecular Biology and Evolution (2020)

Endosymbiosis with chemosynthetic bacteria has enabled many deep-sea invertebrates to thrive at hydrothermal vents and cold seeps, but most previous studies on this mutualism have focused on the bacteria only. Vesicomyid clams dominate global deep-sea chemosynthesis-based ecosystems. They differ from most deep-sea symbiotic animals in passing their symbionts from parent to offspring, enabling intricate coevolution between the host and the symbiont. Here, we sequenced the genomes of the clam Archivesica marissinica (Bivalvia: Vesicomyidae) and its bacterial symbiont to understand the genomic/metabolic integration behind this symbiosis. At 1.52 Gb, the clam genome encodes 28 genes horizontally transferred from bacteria, a large number of pseudogenes and transposable elements whose massive expansion corresponded to the timing of the rise and subsequent divergence of symbiont-bearing vesicomyids. The genome exhibits gene family expansion in cellular processes that likely facilitate chemoautotrophy, including gas delivery to support energy and carbon production, metabolite exchange with the symbiont, and regulation of the bacteriocyte population. Contraction in cellulase genes is likely adaptive to the shift from phytoplankton-derived to bacteria-based food. It also shows contraction in bacterial recognition gene families, indicative of suppressed immune response to the endosymbiont. The gammaproteobacterium endosymbiont has a reduced genome of 1.03 Mb but retains complete pathways for sulfur oxidation, carbon fixation, and biosynthesis of 20 common amino acids, indicating the host's high dependence on the symbiont for nutrition. Overall, the host-symbiont genomes show not only tight metabolic complementarity but also distinct signatures of coevolution allowing the vesicomyids to thrive in chemosynthesis-based ecosystems.
Protein Glycosylation: “New-yet-Old” Target for Immunotherapy
Authors: Jaydeep Bhat, Dieter Kabelitz
Journal: Clinical Cancer Research (2020)

The use of checkpoint monotherapy in treating cancer has limited success. Post-translational modifications (PTM) of proteins such as glycosylation might have clinical implications due to distinct modifications found in diseases and its regulatory role in the immunometabolic gene expression. Such novel mechanistic targets hold great promise for combined immunotherapy.See related article by Shi et al., p. 5990.
Distinct evolutionary paths in chronic lymphocytic leukemia during resistance to the graft-versus-leukemia effect
Authors: Pavan Bachireddy, Christina Ennis, Vinhkhang N. Nguyen, Satyen H. Gohil, Kendell Clement, Sachet A. Shukla, Juliet Forman, Nikolaos Barkas, Samuel Freeman, Natalie Bavli, Liudmila Elagina, Ignaty Leshchiner, Arman W. Mohammad, Nathan D. Mathewson, Derin B. Keskin, Laura Z. Rassenti, Thomas J. Kipps, Jennifer R. Brown, Gad Getz, Vincent T. Ho, Andreas Gnirke, Donna Neuberg, Robert J. Soiffer, Jerome Ritz, Edwin P. Alyea, Peter V. Kharchenko, Catherine J. Wu
Journal: Science Translational Medicine (2020)

The clinical kinetics of CLL relapse after stem cell transplant are underwritten by distinct genetic and epigenetic evolutionary trajectories.
Corrigendum to “Mild photothermal therapy/photodynamic therapy/chemotherapy of breast cancer by Lyp-1 modified docetaxel/IR820 co-loaded micelles”[Biomaterials, 106 (2016) 119–133]
Authors: Wenting Li, Jinrong Peng, Liwei Tan, Jing Wu, Kun Shi, Ying Qu, Xiawei Wei, Zhiyong Qian
Journal: Biomaterials (2020)
Nonfatal Opioid Overdoses at an Urban Emergency Department During the COVID-19 Pandemic
Authors: Taylor A. Ochalek, Kirk L. Cumpston, Brandon K. Wills, Tamas S. Gal, F. Gerard Moeller
Journal: JAMA (2020)

This study compares the numbers of nonfatal, unintentional opioid-related opioid overdoses presenting to a US urban emergency department during the early months of the coronavirus disease 2019 (COVID-19) pandemic (March-June 2020) vs 2019, overall and by age, race/ethnicity, and insurance status.
Transcriptomics and solid tumors: The next frontier in precision cancer medicine
Authors: Apostolia M. Tsimberidou, Elena Fountzilas, Leonidas Bleris, Razelle Kurzrock
Journal: Seminars in Cancer Biology (2020)

Transcriptomics, which encompasses assessments of alternative splicing and alternative polyadenylation, identification of fusion transcripts, explorations of noncoding RNAs, transcript annotation, and discovery of novel transcripts, is a valuable tool for understanding cancer mechanisms and identifying biomarkers. Recent advances in high-throughput technologies have enabled large-scale gene expression profiling. Importantly, RNA expression profiling of tumor tissue has been successfully used to determine clinically actionable molecular alterations. The WINTHER precision medicine clinical trial was the first prospective trial in diverse solid malignancies that assessed both genomics and transcriptomics to match treatments to specific molecular alterations. The use of transcriptome analysis in WINTHER and other trials increased the number of targetable -omic changes compared to genomic profiling alone. Other applications of transcriptomics involve the evaluation of tumor and circulating noncoding RNAs as predictive and prognostic biomarkers, the improvement of risk stratification by the use of prognostic and predictive multigene assays, the identification of fusion transcripts that drive tumors, and an improved understanding of the impact of DNA changes as some genomic alterations are silenced at the RNA level. Finally, RNA sequencing and gene expression analysis have been incorporated into clinical trials to identify markers predicting response to immunotherapy. Many issues regarding the complexity of the analysis, its reproducibility and variability, and the interpretation of the results still need to be addressed. The integration of transcriptomics with genomics, proteomics, epigenetics, and tumor immune profiling will improve biomarker discovery and our understanding of disease mechanisms and, thereby, accelerate the implementation of precision oncology.
A novel nondrug SFRP1 antagonist inhibits catagen development in human hair follicles <i>ex vivo</i>
Authors: M. Bertolini, J. Chéret, D. Pinto, N. Hawkshaw, L. Ponce, H. Erdmann, F. Jimenez, W. Funk, R. Paus
Journal: British Journal of Dermatology (2020)
Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications
Authors: Antonis S. Manolis, Antonis A. Manolis, Theodora A. Manolis, Naomi E. Apostolaki, Evdoxia J. Apostolopoulos, Helen Melita, Niki Katsiki
Journal: Medicinal Research Reviews (2020)

Abstract Mitochondria provide energy to the cell during aerobic respiration by supplying ~95% of the adenosine triphosphate (ATP) molecules via oxidative phosphorylation. These organelles have various other functions, all carried out by numerous proteins, with the majority of them being encoded by nuclear DNA (nDNA). Mitochondria occupy ~1/3 of the volume of myocardial cells in adults, and function at levels of high‐efficiency to promptly meet the energy requirements of the myocardial contractile units. Mitochondria have their own DNA (mtDNA), which contains 37 genes and is maternally inherited. Over the last several years, a variety of functions of these organelles have been discovered and this has led to a growing interest in their involvement in various diseases, including cardiovascular (CV) diseases. Mitochondrial dysfunction relates to the status where mitochondria cannot meet the demands of a cell for ATP and there is an enhanced formation of reactive‐oxygen species. This dysfunction may occur as a result of mtDNA and/or nDNA mutations, but also as a response to aging and various disease and environmental stresses, leading to the development of cardiomyopathies and other CV diseases. Designing mitochondria‐targeted therapeutic strategies aiming to maintain or restore mitochondrial function has been a great challenge as a result of variable responses according to the etiology of the disorder. There have been several preclinical data on such therapies, but clinical studies are scarce. A major challenge relates to the techniques needed to eclectically deliver the therapeutic agents to cardiac tissues and to damaged mitochondria for successful clinical outcomes. All these issues and progress made over the last several years are herein reviewed.
Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function
Authors: Aleksandar Denic, Hisham Elsherbiny, Aidan F. Mullan, Bradley C. Leibovich, R. Houston Thompson, Luisa Ricaurte Archila, Ramya Narasimhan, Walter K. Kremers, Mariam P. Alexander, John C. Lieske, Lilach O. Lerman, Andrew D. Rule
Journal: Journal of the American Society of Nephrology (2020)

Nephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease.To determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6-12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria.Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m2), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence.After a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.