tbuckley/cabot-search huggingface dataset:
Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage
Authors: Douglas Meyer, Jacob Kames, Haim Bar, Anton A. Komar, Aikaterini Alexaki, Juan Ibla, Ryan C. Hunt, Luis V. Santana-Quintero, Anton Golikov, Michael DiCuccio, Chava Kimchi-Sarfaty
Journal: Genome Medicine (2021)

Abstract Background Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest. Methods We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues. Results We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research. Conclusions Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.
O-16 HEPANOVA: Final efficacy and safety results from a phase 2 study of Tumor Treating Fields (TTFields, 150 kHz) concomitant with sorafenib in advanced hepatocellular carcinoma
Authors: E. Gkika, A. Grosu, T. Macarulla, A. Cubillo, M. Pazgan-Simon, T. Seufferlein, Y. Touchefeu
Journal: Annals of Oncology (2021)
Novel<i>Doublesex</i>Duplication Associated with Sexually Dimorphic Development of Dogface Butterfly Wings
Authors: Fernando Rodriguez-Caro, Jennifer Fenner, Shivam Bhardwaj, Jared Cole, Caleb Benson, Alexandra M Colombara, Riccardo Papa, Matthew W Brown, Arnaud Martin, Ryan C Range, Brian A Counterman
Journal: Molecular Biology and Evolution (2021)

Abstract Sexually dimorphic development is responsible for some of the most remarkable phenotypic variation found in nature. Alternative splicing of the transcription factor gene doublesex (dsx) is a highly conserved developmental switch controlling the expression of sex-specific pathways. Here, we leverage sex-specific differences in butterfly wing color pattern to characterize the genetic basis of sexually dimorphic development. We use RNA-seq, immunolocalization, and motif binding site analysis to test specific predictions about the role of dsx in the development of structurally based ultraviolet (UV) wing patterns in Zerene cesonia (Southern Dogface). Unexpectedly, we discover a novel duplication of dsx that shows a sex-specific burst of expression associated with the sexually dimorphic UV coloration. The derived copy consists of a single exon that encodes a DNA binding but no protein-binding domain and has experienced rapid amino-acid divergence. We propose the novel dsx paralog may suppress UV scale differentiation in females, which is supported by an excess of Dsx-binding sites at cytoskeletal and chitin-related genes with sex-biased expression. These findings illustrate the molecular flexibility of the dsx gene in mediating the differentiation of secondary sexual characteristics.
Milk-derived extracellular vesicles alleviate ulcerative colitis by regulating the gut immunity and reshaping the gut microbiota
Authors: Lingjun Tong, Haining Hao, Zhe Zhang, Youyou Lv, Xi Liang, Qiqi Liu, Tongjie Liu, Pimin Gong, Lanwei Zhang, Fangfang Cao, Giorgia Pastorin, Chuen Neng Lee, Xiaoyuan Chen, Jiong-Wei Wang, Huaxi Yi
Journal: Theranostics (2021)

Rationale: Bovine milk constitutes an essential part of human diet, especially for children, due to its enrichment of various nutrients.We recently developed an effective protocol for the isolation of extracellular vesicles from milk (mEVs) and discovered that mEVs contained large amounts of immune-active proteins and modulated the gut immunity and microbiota in healthy mice.Here, we aimed to explore the therapeutic effects of mEVs on inflammatory bowel disease.Methods: MicroRNAs and protein content in mEVs were analyzed by RNA sequencing and proteomics, respectively, followed by functional annotation.Ulcerative colitis (UC) was induced by feeding mice with dextran sulfate sodium.Intestinal immune cell populations were phenotyped by flow cytometry, and the gut microbiota was analyzed via 16S rRNA sequencing.Results: We showed that abundant proteins and microRNAs in mEVs were involved in the regulation of immune and inflammatory pathways and that oral administration of mEVs prevented colon shortening, reduced intestinal epithelium disruption, inhibited infiltration of inflammatory cells and tissue fibrosis in a mouse UC model.Mechanistically, mEVs attenuated inflammatory response via inhibiting TLR4-NF-κB signaling pathway and NLRP3 inflammasome activation.Furthermore, mEVs were able to correct cytokine production disorder and restore the balance between T helper type 17 (Th17) cells and interleukin-10 + Foxp3 + regulatory T (Treg) cells in the inflamed colon.The disturbed gut microbiota in UC was also partially recovered upon treatment with mEVs.The correlation between the gut microbiota and cytokines suggests that mEVs may modulate intestinal immunity via influencing the gut microbiota.Conclusions: These findings reveal that mEVs alleviate colitis by regulating intestinal immune homeostasis via inhibiting TLR4-NF-κB and NLRP3 signaling pathways, restoring Treg/Th17 cell balance, and reshaping the gut microbiota.
Artificial intelligence for gastric cancer: can we make further progress?
Authors: Chika Kusano
Journal: Endoscopy (2021)

In this issue of Endoscopy, Wu et al. report on a real-time artificial intelligence (AI) system that detects early gastric cancer (EGC) and blind spots (areas that were not observed) [1]. The authors first developed a novel system using a deep convolutional neural network to analyze esophagogastroduodenoscopy images of EGC [2]. Thereafter, they refined the existing system by integrating the trained real-time EGC detection model, and called the system ENDOANGEL. ENDOANGEL improved the quality of endoscopic examinations by monitoring blind spots in real time.
Abstract 12013: Trends in Reported Cardiovascular Disease and Hospitalizations in Cancer Patients - Cardio-oncology Patterns Over 14-year From Two Nationally Representative Datasets
Authors: Avirup Guha, Amit K Dey, Elliott Miller, Michael G Fradley, Nihar R Desai, Daniel Addison
Journal: Circulation (2019)

Background: Cancer survival statistics are well documented; however, the true magnitude of cardiac disease among those with cancer remains largely unknown. Hypothesis: We sought to estimate the pro...
Uncovering the novel Enterobacter cloacae complex species responsible for septic shock deaths in newborns: a cohort study
Authors: Delphine Girlich, Souad Ouzani, Cécile Emeraud, Lauraine Gauthier, Rémy A Bonnin, N Le Sache, Mostafa Mokhtari, Isabelle Langlois, Christine Begasse, Nicolas Arangia, Sandra Fournier, Nicolas Fortineau, Thierry Naas, Laurent Dortet
Journal: The Lancet Microbe (2021)

Enterobacter cloacae complex contains nosocomial pathogens responsible for infection outbreaks. Identification at the species level within the E cloacae complex remains difficult. Using whole genome sequencing, our aim was to decipher the transmission routes that led to the death of six of seven neonates who had bacteraemia caused by E cloacae complex isolates in a neonatal intensive care unit (NICU) over a 13 month period.In this cohort study, E cloacae complex isolates were taken from 186 newborns in an NICU: 14 were clinical samples (eg, blood cultures), 728 rectal swab samples, and 38 environmental samples (20 from siphons, 18 from incubators, and one from a mattress). The samples were analysed to decipher the possible role of manual cross transmission or environmental source in an outbreak of fatal septic shocks related to E cloacae complex bacteraemia. After the replacement of the incubators suspected to be the reservoir of some outbreak-related isolates on Feb 1, 2018, E cloacae complex strains were screened again for 10 months (503 rectal swab samples from 163 newborns). The 71 E cloacae complex isolates recovered from screening, clinical, and environmental samples across both study periods were compared by whole genome sequencing. The pathogenicity of E cloacae complex isolates responsible for fatal septic shocks was assessed using a Galleria mellonella in-vivo model.From Dec 9, 2016, to Jan 31, 2018, 249 (34%) of 728 rectal swab samples were positive for E cloacae complex, with 66 (35%) of 186 newborns colonised. E cloacae complex were also recovered from four (20%) of 20 siphons and 11 (61%) of 18 incubators. During this period, whole genome sequencing identified that the isolates responsible for the six fatal septic shocks were all Enterobacter bugandensis. A G mellonella infection model showed a higher virulence of E bugandensis. Genomic analysis highlighted the role of incubators as a long-term reservoir and source of cross contamination, leading to their replacement on Feb 1, 2018. Following incubator replacement, a 10-month follow-up investigation identified a physiological gut colonisation with polyclonal E cloacae complex in 52 (34%) of 163 neonates within a median of 9 days (5-14), but no E cloacae complex-related septic shocks.Despite around 30% of neonates being physiologically colonised with E cloacae complex, fatal sepsis was systematically linked with bacteraemia caused by E bugandensis. Our findings highlight the need for accurate identification methods to detect the hypervirulent species within the E cloacae complex recovered in neonates.Assistance Publique-Hôpitaux de Paris.
Evaluating differential cost growth across individual cancers: Insights from Oncology Care Model data.
Authors: Basit Iqbal Chaudhry, Lucio N. Gordan, Andrew Yue, Lisa Tran, Nora Connor
Journal: Journal of Clinical Oncology (2021)

e18853 Background: Analyzing cost growth in oncology often faces significant challenges, including fragmentation of data for infused vs. oral agents and ascertaining the cost of inpatient care. How differential cost growth at the individual cancer level contributes to aggregate cost growth in oncology is often opaque. We leverage the integrated claims data provided by Medicare for its Oncology Care Model (OCM) pilot to analyze variations across individual cancers with respect to cost growth. Methods: OCM’s innovative methodology creates a natural experiment where costs are compared against a counterfactual comprised of Medicare patients seen in non-OCM practices. Leveraging this differential counterfactual provides an opportunity to gain insight into cost growth for individual cancers compared to oncology as a whole. Specifically, cost growth is measured each Performance Period (PP) with respect to the Baseline Period, from 2012 to 2015. We analytically decomposed and remodeled key quantitative factors in OCM associated with cost dynamics in oncology, including the Trend Factor (TF), which represents non-OCM cost growth. From 124,896 episodes, we sampled with replacement 19,191 episodes from 17 practices between PP1 and PP6 using empirical data distributions. We assumed neutral novel therapy and experience adjustments and then compared the overall TF to the remodeled cancer-level TF, reaggregated from the individual episodes. Results: Reallocating the TF reveals that cost growth among cancer types is highly variable in the broader Medicare population. Cost growth at the individual cancer level varied from +99.3% to -14.3%. Of the 21 OCM cancers, 18 have TFs greater than zero, indicating cost growth in the non-OCM Medicare population since the Baseline Period. Four have a TF greater than 50%. Three cancer types show decreasing costs relative to the baseline period: intestinal cancer, MDS, and CNS tumor. Conclusions: Significant variation exists across individual cancer subtypes in terms of cost growth. Aggregate analyses of cancer at large have insufficient specificity to rationalize payment mechanisms. Payment reform efforts within cancer care should directly address dynamics at the individual cancer or cancer subtype level in order to provide more valid considerations for expected resource utilization, including in future payment policies. [Table: see text]
Essential role of a ThPOK autoregulatory loop in the maintenance of mature CD4+ T cell identity and function
Authors: Jayati Basu, Bernardo S. Reis, Suraj Peri, Jikun Zha, Xiang Hua, Lu Ge, Kyle Ferchen, Emmanuelle Nicolas, Philip Czyzewicz, Kathy Q. Cai, Yinfei Tan, Juan I. Fuxman Bass, Albertha J. M. Walhout, H. Leighton Grimes, Sergei I. Grivennikov, Daniel Mucida, Dietmar J. Kappes
Journal: Nature Immunology (2021)
Proportion of CD34+CD38- Leukemia Stem Cell Fraction Predicts Relapse Rate after Umbilical Cord Blood Transplantation in Acute Myeloid Leukemia with Adverse Karyotype
Authors: Shinsuke Takagi, Akiko Yoneyama, Naoyuki Uchida, Takashi Mitsuki, Mitsuhiro Yuasa, Kosei Kageyama, Daisuke Kaji, Yuki Taya, Aya Nishida, Kazuya Ishiwata, Hisashi Yamamoto, Go Yamamoto, Yuki Asano-Mori, Yukako Koike, Atsushi Wake, Shigeyoshi Makino, Shuichi Taniguchi
Journal: Blood (2017)
A Periodic Problem
Authors: Allison Kratka, Nicholas Yozamp, Anand Vaidya, Ellen Marqusee
Journal: New England Journal of Medicine (2021)

A 27-year-old man presented to the emergency department with weakness in both legs that was so severe he could not stand. He reported having several similar episodes of leg weakness during the preceding 6 months that had resolved spontaneously within 30 to 60 minutes. . . .
Primary Care Health Professional Shortage Area Designations Before and After the Affordable Care Act’s Shortage Designation Modernization Project
Authors: Christopher A. Scannell, Jacob K. Quinton, Nicholas J. Jackson, Yusuke Tsugawa
Journal: JAMA Network Open (2021)

This cross-sectional study evaluates whether the Patient Protection and Affordable Care Act (ACA) Shortage Designation Modernization Project is associated with changes in primary care health professional shortage area (PC-HPSA) designations.
Abstract 8309: Adiponectin Deficiency Exacerbates Endothelial Dysfunction By Increasing Inflammation In High-fat Diet Induced Obese Mice
Authors: Sewon Lee, Cuihua Zhang
Journal: Circulation (2011)

Adiponectin (APN) is a 30-kDa protein exclusively secreted by adipose tissue. Clinical data show obese and type 2 diabetic patients have decreased APN levels in the circulation. Previously, we showed that APN is deficient in the serum and in aorta protein expression in type 2 diabetic mice ( db/db , Lepr db ), which suggests APN may play an important role in vascular dysfunction and the development of type 2 diabetes. Accordingly, we hypothesized that APN deficiency will impair endothelial function in aortas in high fat diet (HF) induced obese mice. To test this hypothesis, we fed HF diet (60% calories from fat) in wild type (WT) and APN knock-out (APNKO) mice for 18 weeks and studied vascular function of aorta ex vivo. Endothelium-dependent vasodilator acetylcholine (Ach)-induced vasodilation was blunted in APNKO+HF compare to WT+HF, but sodium nitroprusside (SNP)-induced endothelium-independent vasodilation was identical. Previously, we showed that adenoviral delivery of APN (Ad-APN) improved endothelial function in diabetic mice compare to control virus treatment (Ad-βgal). Real-time PCR results showed that mRNA gene expression of TNFα, IL-6 and intercellular adhesion molecule-1(ICAM-1) was higher in db/db aortas compared to control mice, suggesting that inflammation and recruitment of immune cells may contribute to endothelial dysfunction. However, Ad-APN treatment decreased TNFα, IL-6 and ICAM-1 suggesting APN may suppress inflammation and adhesion molecules. This suggests that APN may contribute to an increase in nitric oxide bioavailability by decreasing inflammation and recruitment of immune cells in the aorta. APN appears to play an important role in the prevention of vascular dysfunction in the aortas by preventing inflammation and immune response the animal and infers a similar role may occur is in obese/diabetic patients.
Glycosylation of PAMAM dendrimers significantly improves tumor macrophage targeting and specificity in glioblastoma
Authors: Rishi Sharma, Kevin Liaw, Anjali Sharma, Ambar Jimenez, Michelle Chang, Sebastian Salazar, Imaan Amlani, Sujatha Kannan, Rangaramanujam M. Kannan
Journal: Journal of Controlled Release (2021)
P10-7 Immunological and nutritional predictors for first-line chemoimmunotherapy in advanced non-small cell lung cancer
Authors: Takayuki Takeda, Yuri Ogura, Nobutaka Kataoka, Yusuke Kunimatsu, Yusuke Tachibana, Takumi Sugimoto, Nozomi Tani, Izumi Sato, Kazuki Hirose, Daishiro Kato
Journal: Annals of Oncology (2021)
Immunopolarization-regulated 3D printed-electrospun fibrous scaffolds for bone regeneration
Authors: Xingzhi Liu, Mimi Chen, Junchao Luo, Huan Zhao, Xichao Zhou, Qiaoli Gu, Huilin Yang, Xuesong Zhu, Wenguo Cui, Qin Shi
Journal: Biomaterials (2021)
P-51 Baseline characteristics of patients enrolled in the CAPSTAN study: A European retrospective study in BRAFV600E-mutant metastatic colorectal cancer patients
Authors: E. Martinelli, B. Asselain, C. Cremolini, T. Mazard, J. Vidal, I. Virchow, D. Tougeron, H. Berradi, C. Castagné, D. Arnold
Journal: Annals of Oncology (2021)
Response to mRNA vaccination for COVID-19 among patients with multiple myeloma
Authors: Samuel D. Stampfer, Marissa-Skye Goldwater, Scott Jew, Sean Bujarski, Bernard Regidor, David Daniely, Haiming Chen, Ning Xu, Mingjie Li, Tracy Green, Eddie Fung, Elias Aquino, Regina Swift, Shahrooz Eshaghian, Kurt Preugschat, Aaron J. Feinstein, Tanya M. Spektor, James R. Berenson
Journal: Leukemia (2021)
Fiona Godlee to step down as The BMJ ’s editor in chief
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Fiona Godlee is to resign as editor in chief of The BMJ at the end of this year, after more than 16 years in the role.

Godlee first joined the journal as an assistant editor in 1990 and became editor in chief in March 2005, the first woman to lead it since its inception in 1840.

Under her editorship The BMJ has become firmly established as one of the world’s most influential and most widely read medical journals, defined by its mission to work towards a healthier world for all. The journal’s impact factor, a measure of the importance or rank of a journal, has risen from 7 in 2005 to 39.8 today, and in the past five years worldwide usage on bmj.com has grown from around a million unique users …
Immunotherapies and COVID-19 mortality: a multidisciplinary open data analysis based on FDA’s Adverse Event Reporting System
Authors: Maximilian Pistor, Andreas G F Hoepner, Yanan Lin, Simon Jung, Claudio L Bassetti, Andrew Chan, Anke Salmen, Robert Hoepner
Journal: Annals of the Rheumatic Diseases (2021)

During the COVID-19 pandemic, the risks and potential benefits of immunotherapies for the treatment of autoimmune disorders are still not well defined, and many cohort studies neither took the epidemiological dynamics of COVID-19 nor the potential capacities of the local healthcare systems in their outcome analysis into account. Due to a pronounced heterogeneity in the outcome reports of different participating countries, the large ‘COVID-19 Global Rheumatology Alliance registry’ addressed this issue using a ‘cluster design’ and shed light on factors associated with a more severe COVID-19 course in their study population.1 We here present data of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS),2 a postmarketing, self-reporting, open-access pharmacovigilance platform that contains international data of COVID-19 cases. Sources of FAERS are voluntary reports from healthcare professionals and consumers. We combine this data set with local measurements of the course of the pandemic (from Oxford University’s ‘Our World in Data’3) and the potential resiliency of the respective healthcare systems (from ‘World Bank’; see online supplemental table 1 for full source information). Only patients with the diagnosis of an autoimmune disorder and a single immunotherapy (required group size: n≥100) at the time point of COVID-19 were analysed by multivariable regression analysis (online supplemental figure 1), limiting the generalisability of our data, for example, concerning combination therapy scenarios (online supplemental figure 1).### Supplementary data

[annrheumdis-2021-220679supp001.pdf] 

The mean age of patients in our cohort (n=2103) was 51.3 years (range 3–92 years; SD 14.9), female sex was more prevalent (1372/2103, 65.2%) and the majority of cases was reported in the USA/Canada (1285/2103, 61.1%). Inflammatory joint disease (846/2103, 40.2%), multiple sclerosis (474/2103, 22.5%) and inflammatory skin disease (435/2103, 20.7%) were the most prevalent diagnoses. Anti-tumour necrosis factor α (TNFα) therapies were the most frequently used medications for the …