tbuckley/cabot-search huggingface dataset:
Abstract A26: Comparison of DNA extraction kits for metagenomic studies in feces
Authors: Isabella Kuniko T. Takenaka, Bruno S. Moda, Thaís F. Bartelli, Maria G. Amorim, Gabriela E. Albuquerque, Andrew M. Thomas, Emmanuel Dias-Neto, Diana N. Nunes
Journal: Cancer Research (2020)

Abstract DNA extraction is a critical step in metagenomic studies since it requires the proper lysis of cell walls, allowing the recovery of nucleic acids that would represent the total diversity of communities. Recent studies indicated that the use of different DNA extraction methods in the same sample yielded distinct microbial profiles, highlighting the importance of standardization in DNA extraction methodologies to accurately measure the human microbiome. These issues are even more critical when limiting amounts of samples are available, or when studies target communities with reduced abundance, such as fungi, which represents only 0.1% of total gut microbiota, as has been poorly explored. Here we investigated the performance of three commercial kits for DNA extraction from human fecal samples: QIAamp DNA Stool Mini Kit (Qiagen), E.Z.N.A. Stool DNA Kit (Omega), and ZymoBIOMICS DNA Kit (Zymo), all with or without adding an enzymatic extraction with MetaPolyzyme (MAC4L - Sigma), in an attempt to improve the microbiome community profiling. After extraction, DNA-quality and yield were evaluated using Qubit and real-time PCR, V4-V5 16S rRNA and ITS2 followed by DNA sequencing, as well as further analysis using shotgun DNA sequencing. No significant differences were observed in DNA yield as evaluated by Qubit; an average of 40.3 ng/ul of DNA was obtained for all samples and kits. For both fungi and bacteria analysis, the addition of MAC4L in the extraction protocol apparently did not change the alpha diversity (observed and Shannon) for both individuals. Our analysis for samples extracted with different kits, with or without MAC4L, indicated the percentage of reads from bacteria to vary between 85-90%, whereas fungi were between 0.29-0.49%. Human DNA was also found, as expected, and relative amounts varied from 0.1 to 0.3%. qPCR showed that for all kits up to 50ng of DNA/15uL reaction can be safely used, with no significant DNA polymerase inhibition. These results showed similar efficacy for the three kits in representing bacteria and fungi from feces, and maybe because all these kits had a bead-beading step we had no clear benefits from adding extra enzymatic digestion steps with MAC4L. Finally, we decided to use the Omega kit in our lab, since it combines a simple extraction protocol and is reliable and cost-effective. Citation Format: Isabella Kuniko T. Takenaka, Bruno S. Moda, Thaís F. Bartelli, Maria G. Amorim, Gabriela E. Albuquerque, Andrew M. Thomas, Emmanuel Dias-Neto, Diana N. Nunes. Comparison of DNA extraction kits for metagenomic studies in feces [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A26.
Dendrimer-conjugated glutaminase inhibitor selectively targets microglial glutaminase in a mouse model of Rett syndrome
Authors: Elizabeth Smith Khoury, Anjali Sharma, Rajasekhar R Ramireddy, Ajit G. Thomas, Jesse Alt, Amanda Fowler, Rana Rais, Takashi Tsukamoto, Mary E. Blue, Barbara Slusher, Sujatha Kannan, Rangaramanujam M. Kannan
Journal: Theranostics (2020)

Background: Elevated glutamate production and release from glial cells is a common feature of many CNS disorders. Inhibitors of glutaminase (GLS), the enzyme responsible for converting glutamine to glutamate have been developed to target glutamate overproduction. However, many GLS inhibitors have poor aqueous solubility, are unable to cross the blood brain barrier, or demonstrate significant toxicity when given systemically, precluding translation. Enhanced aqueous solubility and systemic therapy targeted to activated glia may address this challenge. Here we examine the impact of microglial-targeted GLS inhibition in a mouse model of Rett syndrome (RTT), a developmental disorder with no viable therapies, manifesting profound central nervous system effects, in which elevated glutamatergic tone, upregulation of microglial GLS, oxidative stress and neuroimmune dysregulation are key features. Methods: To enable this, we conjugated a potent glutaminase inhibitor, N-(5-{2-[2-(5-amino-[1,3,4]thiadiazol-2-yl)-ethylsulfanyl]-ethyl}-[1,3,4]thiadiazol-2-yl)-2-phenyl-acetamide (JHU29) to a generation 4 hydroxyl PAMAM dendrimer (D-JHU29). We then examined the effect of D-JHU29 in organotypic slice culture on glutamate release. We also examined GLS activity in microglial and non-microglial cells, and neurobehavioral phenotype after systemic administration of D-JHU29 in a mouse model of RTT. Results: We report successful conjugation of JHU29 to dendrimer resulting in enhanced water solubility compared to free JHU29. D-JHU29 reduced the excessive glutamate release observed in tissue culture slices in a clinically relevant Mecp2-knockout (KO) RTT mouse. Microglia isolated from Mecp2-KO mice demonstrated upregulation of GLS activity that normalized to wild-type levels following systemic treatment with D-JHU29. Neurobehavioral assessments in D-JHU29 treated Mecp2-KO mice revealed selective improvements in mobility. Conclusion: These findings demonstrate that glutaminase inhibitors conjugated to dendrimers are a viable mechanism to selectively inhibit microglial GLS to reduce glutamate production and improve mobility in a mouse model of RTT, with broader implications for selectively targeting this pathway in other neurodegenerative disorders.
Phase 1/2 Study of Orociep All Oral Regimen with Idarubicin, Cyclophosphamide, Etoposide, Prednisolone in Combination to Intravenous Rituximab in Elderly Patients with Disseminated High Grade Non Hodgkin Lymphoma. Final Analysis
Authors: Stephanie Guidez, Laurence lacotte-Thierry, Cecile Tomowiak, Antoine Machet, Carine Motard, Anthony Levy, Cécile Gruchet, Florence Sabirou, Arthur Bobin, Niels Moya, Thomas Systchenko, Jocelyn Barrier, Carine le Du, Emmanuel Fleck, Diane Chuillet-Moreau, Michele Chabin, Xavier Leleu, Joelle Guilhot, Vincent Delwail
Journal: Blood (2017)
The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1
Authors: Catherine L. Carmichael, Jueqiong Wang, Thao Nguyen, Oluseyi Kolawole, Aissa Benyoucef, Charlotte De Mazière, Anna R. Milne, Sona Samuel, Kevin Gillinder, Soroor Hediyeh-zadeh, Anh N. Q. Vo, Yizhou Huang, Kathy Knezevic, William R. L. McInnes, Benjamin J. Shields, Helen Mitchell, Matthew E. Ritchie, Tim Lammens, Beatrice Lintermans, Pieter Van Vlierberghe, Nicholas C. Wong, Katharina Haigh, Julie A. I. Thoms, Emma Toulmin, David J. Curtis, Ethan P. Oxley, Ross A. Dickins, Dominik Beck, Andrew Perkins, Matthew P. McCormack, Melissa J. Davis, Geert Berx, Johannes Zuber, John E. Pimanda, Benjamin T. Kile, Steven Goossens, Jody J. Haigh
Journal: Blood (2020)
Abstract 16337: Endoplasmic Reticulum Stress Contributes to Cardiomyocyte Apoptosis in Trauma-Induced Secondary Cardiac Injury
Authors: Zi Yan, Jin-Ling He, Dan Li, Xian-yan Zeng, Na Ning, Jie Wang, Li Wang, Jin Wang, Xiang-Ying Jiao, Ji-Min Cao, Hui-Rong Liu, Zhong-Mei He
Journal: Circulation (2017)

Introduction: Numerous studies indicate that accumulation of misfolded proteins and alteration of Ca2+ homeostasis initiate endoplasmic reticulum (ER) stress and thus trigger apoptosis. Myocardial ...
Lipid efflux mechanisms, relation to disease and potential therapeutic aspects
Authors: David Castaño, Chutima Rattanasopa, Vera F. Monteiro-Cardoso, Maria Corlianò, Yiran Liu, Shiqi Zhong, Mihaela Rusu, Elisa A. Liehn, Roshni R. Singaraja
Journal: Advanced Drug Delivery Reviews (2020)
Chronic Daily Headache
Authors: David W. Dodick
Journal: New England Journal of Medicine (2006)

A 36-year-old woman with a long history of catamenial migraines had had a headache almost every day for a year. The background headache was mild, but it became severe and incapacitating at least twice a week, interfering with work and sleep. She took six to eight tablets containing a combination of aspirin, acetaminophen, and caffeine per day, with minimal relief. She did not have fever, weight loss, diplopia, or tinnitus. Her headaches were not exacerbated by a Valsalva maneuver or positional change. Her physical examination was normal. How should she be evaluated and treated?
Covid-19: Doctors face shortages of vital drugs, gases, and therapeutics, survey finds
Authors: Abi Rimmer
Journal: BMJ (2020)

Shortages of items such as antibiotics, anaesthetic drugs, and painkillers have forced doctors to offer their patients less effective treatments, a BMA survey has found.

The survey, which received 16 343 responses from doctors across the UK, was conducted between 28 and 30 April.

Of the 14 028 doctors who answered a question on shortages of medicines, medical gases, and other therapeutics, 4% (579) said they experienced such shortages “most of the time.” A further 24% (3362) said they experienced shortages “some of the time.”

A third (2671of 8373) …
Association Between High-grade Myelodysplastic Syndrome and Cutaneous Langerhans Cell Histiocytosis Suggested by Next-Generation Sequencing
Authors: Sharad Khurana, Jason C. Sluzevich, Rong He, Danielle K. Reimer, Mohamed A. Kharfan-Dabaja, James M. Foran, Liuyan Jiang
Journal: JAMA Dermatology (2020)

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Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals
Authors: Dapeng Ju, Wei Zhang, Jiawei Yan, Haijiao Zhao, Wei Li, Jiawen Wang, Meimei Liao, Zhancong Xu, Zhiqiang Wang, Guanshen Zhou, Long Mei, Nannan Hou, Shuhua Ying, Tao Cai, She Chen, Xiaowen Xie, Luhua Lai, Chao Tang, Noheon Park, Joseph S. Takahashi, Niu Huang, Xiangbing Qi, Eric Erquan Zhang
Journal: Science Translational Medicine (2020)

A compound that disassembles the circadian repressive super-complex can reset circadian phase and relieve jet lag in mice.
Determining the Appropriate Risk-Adapted Screening Age for Familial Breast Cancer
Authors: Kari Hemminki
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Covid-19: Number of Germans infected could be 10 times higher than official estimates
Authors: Ned Stafford
Journal: BMJ (2020)

The number of people in Germany infected with covid-19, could be 10 times higher than official government estimates, according to a new study by University of Bonn researchers.1

The Heinsberg study is based on an investigation in Gangelt, a town of around 13 000 people in the North Rhine-Westphalia district of Heinsberg. Following the annual carnival celebration in February, the district became the first area in Germany with a massive covid-19 outbreak.

The study, which has been uploaded to a preprint server, found that about 15% of Gangelt residents had been infected with covid-19, compared with the official infection rate at the time of only 3%. The higher infection rate for …
Risk of first and recurrent serious infection in sarcoidosis: a Swedish register-based cohort study
Authors: Marios Rossides, Susanna Kullberg, Anders Eklund, Daniela Di Giuseppe, Johan Grunewald, Johan Askling, Elizabeth V. Arkema
Journal: European Respiratory Journal (2020)

Serious infections impair quality of life and increase costs. Our aim was to determine if sarcoidosis is associated with a higher rate of serious infection and whether this varies by age, sex, time since diagnosis or treatment status around diagnosis. We compared individuals with sarcoidosis (at least two International Classification of Diseases codes in the Swedish National Patient Register 2003–2013; n=8737) and general population comparators matched 10:1 on age, sex and residential location (n=86 376). Patients diagnosed in 2006–2013 who were dispensed at least one immunosuppressant ±3 months from diagnosis (Swedish Prescribed Drug Register) were identified. Cases and comparators were followed in the National Patient Register for hospitalisations for infection. Using Cox and flexible parametric models, we estimated adjusted hazard ratios (aHR) and 95% confidence intervals for first and recurrent serious infections (new serious infection &gt;30 days after previous). We identified 895 first serious infections in sarcoidosis patients and 3881 in comparators. The rate of serious infection was increased 1.8-fold in sarcoidosis compared to the general population (aHR 1.81, 95% CI 1.65–1.98). The aHR was higher in females than males and during the first 2 years of follow-up. Sarcoidosis cases treated with immunosuppressants around diagnosis had a three-fold increased risk, whereas nontreated patients had a 50% increased risk. The rate of serious infection recurrence was 2.8-fold higher in cases than in comparators. Serious infections are more common in sarcoidosis than in the general population, particularly during the first few years after diagnosis. Patients who need immunosuppressant treatment around diagnosis are twice as likely to develop a serious infection than those who do not.
Postcolonoscopy colorectal cancers in average-risk Korean subjects with a normal initial colonoscopy.
Authors: Han Hee Lee, Hyun Ho Choi, Chun-Hyun Lim, Hyung-Keun Kim, Sung Soo Kim, Hiun-Suk Chae, Hyunjung Cho, Young-Seok Cho
Journal: Journal of Clinical Oncology (2016)

526 Background: There are relatively few studies regarding the incidence of postcolonoscopy colorectal cancer (PCCRC) in Asian countries. We evaluated the characteristics of PCCRC in average-risk Korean subjects. Methods: This study included subjects who were ≥ 50 years of age and had undergone a first completed colonoscopy between January 2001 and December 2004, at which no baseline adenoma had been detected, followed by a second colonoscopy 1–5 years later. The incidence and characteristics of advanced neoplasia in these subjects were assessed. Results: A total of 343 subjects underwent follow-up colonoscopy within 5 years. Seventy-three (21.3%) subjects were found to have at least one adenoma upon follow-up colonoscopy. Advanced adenoma was found in eight (2.3%) subjects, and non-advanced adenomas were found in 65 (19.0%). Five patients (1.5%) were diagnosed with invasive CRC following a normal colonoscopy. The putative reason for the PCCRCs was missed lesions in two (40.0%) and new cancer in three (60.0%) cases. Conclusions: The risk of advanced neoplasia (including PCCRCs) within 5 years after a normal baseline colonoscopy in our cohort was not low. Considering that 40% of PCCRCs were attributable to missed lesions, our results emphasize the need for technical improvement of colonoscopic examinations to improve adenoma detection.
Improving T Cell Therapy for Cancer
Authors: Ann M. Leen, Cliona M. Rooney, Aaron E. Foster
Journal: Annual Review of Immunology (2006)

Adoptive transfer of antigen-specific T lymphocytes is a powerful therapy for the treatment of opportunistic disease and some virus-associated malignancies such as Epstein-Barr virus-positive post-transplant lymphoproliferative disease. However, this strategy has been less successful in patients with nonviral cancers owing to their many and varied immune evasion mechanisms. These mechanisms include downregulation of target antigens and antigen-presenting machinery, secretion of inhibitory cytokines, and recruitment of regulatory immune cells to the tumor site. With increased understanding of the tumor microenvironment and the behavior and persistence of ex vivo-manipulated, adoptively transferred T cells, two novel approaches for increasing the efficacy of T cell therapy have been proposed. The first involves genetic modification of tumor-specific T cells to improve their biological function, for example by augmenting their ability to recognize tumor cells or their resistance to tumor-mediated immunosuppression. The second requires modifications to the host environment to improve the homeostatic expansion of infused T cells or to eliminate inhibitory T cell subsets. In this review, we discuss current, promising strategies to improve adoptive T cell therapy for the treatment of cancer.
Factors Associated With Urgent Care Reliance and Outpatient Health Care Use Among Children Enrolled in Medicaid
Authors: Rebecca R. Burns, Elizabeth R. Alpern, Jonathan Rodean, Therese Canares, Brian R. Lee, Matt Hall, Amanda Montalbano
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Urgent care (UC) centers are a growing option to address children's acute care needs, which may cause unanticipated changes in health care use. <h3>Objectives</h3> To identify factors associated with high UC reliance among children enrolled in Medicaid and examine the association between UC reliance and outpatient health care use. <h3>Design, Setting, and Participants</h3> A retrospective cohort study used deidentified data on 4 133 238 children from the Marketscan Medicaid multistate claims database to calculate UC reliance and outpatient health care use. Children were younger than 19 years, with 11 months or more of continuous Medicaid enrollment and 1 or more UC, emergency department (ED), primary care provider (PCP; physician, advanced practice nurse, or physician assistant; well-child care [WCC] or non-WCC), or specialist outpatient visit during the 2017 calendar year. Statistical analysis was conducted from November 11 to 26, 2019. <h3>Exposures</h3> Urgent care, ED, PCP (WCC and non-WCC), and specialist visits based on coded location of services. <h3>Main Outcomes and Measures</h3> Urgent care reliance, calculated by the number of UC visits divided by the sum of total outpatient (UC, ED, PCP, and specialist) visits. High UC reliance was defined as UC visits totaling more than 33% of all outpatient visits. <h3>Results</h3> Of 4 133 238 children in the study, 2 090 278 (50.6%) were male, with a median age of 9 years (interquartile range, 4-13 years). A total of 223 239 children (5.4%) had high UC reliance. Children 6 to 12 years of age were more likely to have high UC reliance compared with children 13 to 18 years of age (adjusted odds ratio, 1.07; 95% CI, 1.06-1.09). Compared with white children, black children (adjusted odds ratio, 0.81; 95% CI, 0.81-0.82) and Hispanic children (adjusted odds ratio, 0.61; 95% CI, 0.60-0.61) were less likely to have high UC reliance. Adjusted for age, sex, race/ethnicity, and presence of chronic or complex conditions, children with high UC reliance had significantly fewer PCP encounters (WCC: adjusted rate ratio, 0.60; 95% CI, 0.60-0.61; and non-WCC: adjusted rate ratio, 0.41; 95% CI, 0.41-0.41), specialist encounters (adjusted rate ratio, 0.31; 95% CI, 0.31-0.31), and ED encounters (adjusted rate ratio, 0.68; 95% CI, 0.67-0.68) than children with low UC reliance. <h3>Conclusions and Relevance</h3> High UC reliance occurred more often in healthy, nonminority, school-aged children and was associated with lower health care use across other outpatient settings. There may be an opportunity in certain populations to ensure that UC reliance does not disrupt the medical home model.
Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies
Authors: Jason Cham, Li Zhang, Serena Kwek, Alan Paciorek, Tao He, Grant Fong, David Y Oh, Lawrence Fong
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background CTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF. Methods We used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman’s rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints. Results While melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=−0.81, p&lt;0.001 vs r=−0.59, p=0.02). Trial registration numbers NCT00064129 ; NCT01363206 .
Covid-19: doctors must take control of their wellbeing
Authors: Gemma Simons, David S Baldwin
Journal: BMJ (2020)

There is never a good time for a pandemic, but covid-19 kicked doctors while we were down. Between 50%1 and 80%2 of us were already burnt out. We went on strike, left traditional training routes, and retired early, and now we are asked, and volunteering, to “doctor on.” In the year before covid-19, policy documents from the Society of …