tbuckley/cabot-search huggingface dataset:
Single-nucleotide variants in TGFB1, TGFBR2, IL17A, and IL17F immune response genes contribute to follicular lymphoma susceptibility and aggressiveness
Authors: Guilherme Rossi Assis-Mendonça, Gustavo Jacob Lourenço, Márcia Torresan Delamain, Vladmir Cláudio Cordeiro de Lima, Gisele Wally Braga Colleoni, Cármino Antônio de Souza, Fernando Augusto Soares, Carmen Silvia Passos Lima, José Vassallo
Journal: Blood Cancer Journal (2020)
Covid-19: Empty chairs mark US deaths
Authors: Alison Shepherd
Journal: BMJ (2020)

Although cells in layer 4 of cat striate cortex represent the first stage in the cortical processing of visual information, they have considerably more complicated receptive field properties than the afferents to the layer from the lateral geniculate nucleus. In considering how these properties are generated, we have focused on the intrinsic cortical circuitry, and particularly on the projection to layer 4 from layer 6. Layer 6 pyramidal cells were injected with horseradish peroxidase and examined at the light and electron microscopic level. The labeled axon terminals were found to form asymmetric synapses and to show a strong preference for contacting dendritic shafts. Serial reconstruction of dendrites postsynaptic to labeled layer 6 cell axon terminals showed that a large proportion of the postsynaptic dendrites belonged to smooth and sparsely spiny stellate cells, suggesting a selective innervation of these cell types. In contrast, the geniculate projection to layer 4 made synapses primarily with dendritic spines and, as a result, the large majority of terminals ended on spiny cells. Since smooth and sparsely spiny stellate cells are thought to mediate inhibition within the cortex, we suggest that one effect of the layer 6 to layer 4 projection could be to contribute to inhibitory features of the receptive fields of layer 4 cells.
Factors associated with time to targeted therapy for patients with metastatic lung cancer with driver mutations.
Authors: Suwei Wang, Hu Huang, Elisabeth Scheufele, Yull Edwin Arriaga, Gretchen Purcell Jackson, Irene Dankwa-Mullan
Journal: Journal of Clinical Oncology (2020)

120 Background: Targeted therapies are superior to chemotherapy in metastatic lung cancer with driver gene mutations. Delays in initiation of targeted therapies may result in faster symptom progression, decline in quality of life, and shortened survival. We examined factors associated with time to initiation of targeted therapy (TTT) in patients with metastatic lung cancer with selected driver mutations. Methods: In this retrospective cohort study, IBM MarketScan claims data was used to identify patients who had an initial diagnosis of metastatic lung cancer, defined as continuous insurance enrollment 12 months pre- to 6 months post-diagnosis, with tumor biomarker (i.e., EGFR, ALK, ROS1, BRAF V600E, NTRK)-directed targeted therapy performed within 6 months of the initial diagnosis, during the timeframe of 1/1/2013 to 12/31/2018. Trends in TTT were evaluated with Wilcoxon–Mann–Whitney. Quantile regression, a robust model that analyzed factors on different outcome-related quantiles, was used to identify associations among TTT and covariates including age, sex, comorbidity, insurance type, and US region. Results: Among 8977 patients identified with an initial diagnosis of metastatic lung cancer, 710 (7.9%) received targeted therapies within the 6-month timeframe, and 1040 (12%) had tumor biomarker testing performed. The overall median TTT was 21 days (IQR = 36 days). Median TTT decreased from 25 days in 2013 to 18 days in 2018 (p = 0.03). Factors associated with longer TTT (median, 50% quantile) were increasing age (p = 0.04), cardiovascular disease (“CVD”, p = 0.03), HIV (p = 0.04), and mild liver disease (p = 0.05). For the lower quantile ( &lt; = 1 day, 5% quantile), female sex (p = 0.01), HIV (p = 0.04), and mild liver disease (p = 0.002) were associated with longer TTT. Having a PPO health plan extended TTT (p = 0.05) at the upper quantile (79 days, 90% quantile). Conclusions: Our study showed an encouraging 5-year trend of the median TTT decreasing by 28%. Numerous factors associated with longer TTT included increasing age, CVD, HIV, mild liver disease, female sex, and PPO plan. This study provides insights into patient-related factors associated with longer time to initiation of targeted therapies for patients with metastatic lung cancer with driver mutations. Additional research is needed to identify the reasons for longer TTT and to develop strategies to expedite delivery of optimal therapies.
Root-Secreted Coumarins and the Microbiota Interact to Improve Iron Nutrition in Arabidopsis
Authors: Christopher J. Harbort, Masayoshi Hashimoto, Haruhiko Inoue, Yulong Niu, Rui Guan, Adamo D. Rombolà, Stanislav Kopriva, Mathias J.E.E.E. Voges, Elizabeth S. Sattely, Ruben Garrido-Oter, Paul Schulze-Lefert
Journal: Cell Host & Microbe (2020)

Plants benefit from associations with a diverse community of root-colonizing microbes. Deciphering the mechanisms underpinning these beneficial services are of interest for improving plant productivity. We report a plant-beneficial interaction between Arabidopsis thaliana and the root microbiota under iron deprivation that is dependent on the secretion of plant-derived coumarins. Disrupting this pathway alters the microbiota and impairs plant growth in iron-limiting soil. Furthermore, the microbiota improves iron-limiting plant performance via a mechanism dependent on plant iron import and secretion of the coumarin fraxetin. This beneficial trait is strain specific yet functionally redundant across phylogenetic lineages of the microbiota. Transcriptomic and elemental analyses revealed that this interaction between commensals and coumarins promotes growth by relieving iron starvation. These results show that coumarins improve plant performance by eliciting microbe-assisted iron nutrition. We propose that the bacterial root microbiota, stimulated by secreted coumarins, is an integral mediator of plant adaptation to iron-limiting soils.
Effect of rurality and neighborhood disadvantage on clinical trial interest and decision-making style in patients with cancer living in the Deep South.
Authors: Nicole Caston, Courtney Williams, Star Ye, Cameron Pywell, Stacey A. Ingram, Elaine Yu, Monica S. Aswani, Andres Azuero, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2020)

110 Background: Patients living in rural or disadvantaged settings are historically underrepresented in clinical trials. This study sought to understand associations between neighborhood characteristics and both interest in clinical trial participation and decision-making style preference. Methods: This cross-sectional study used patient-reported outcome data from patients with cancer treated at the University of Alabama at Birmingham from January 2017 to May 2019. Rural-Urban Commuting Area Codes (RUCA) scores were used to determine rurality of patient residence. Area Deprivation Index (ADI) values (range 0-100) were used to identify patients living in the most disadvantaged (top 15%) census block groups. The Control Preferences Scale captured decision-making preference. Likelihood of interest in clinical trial participation by rurality and neighborhood disadvantage was estimated using risk ratios (RR) and 95% confidence intervals (CI) from modified Poisson regression models. Multinomial regression was used to calculate RRs and 95% CIs estimating likelihood of preferred decision-making style by rurality and neighborhood disadvantage. Models were adjusted for age, sex, race, cancer type, cancer stage, ECOG performance status, and phase of care. Results: Of 1005 patients with cancer, mean age was 67 (SD 11), 68% were female, and 74% white. Gynecologic cancer (32%) was the most prevalent diagnosis, followed by hematologic (20%) and breast (15%) cancer. Of this sample, 16% of patients lived in a rural setting and 18% lived in a disadvantaged neighborhood. Interest in clinical trial participation was no different for patients living in rural vs. urban (RR 0.93, 95% CI 0.73-1.17) or disadvantaged vs. non-disadvantaged neighborhoods (RR 0.88, 95% CI 0.69-1.13). Patients living in rural vs. urban settings trended toward increased likelihood of preferring physician- to patient-driven decision-making (RR 1.67, 95% CI 0.95-2.94). Patients living in disadvantaged vs. non-disadvantaged neighborhoods trended toward increased likelihood of preferring physician- to patient-driven decision-making (RR 1.39, 95% CI 0.82-2.35). Conclusions: Though clinical trial participation interest was similar, patients with cancer living in rural vs. urban settings trended toward increased likelihood of preferring physician- vs. patient-driven decision-making. Opportunities exist for providers to engage historically underrepresented patients for trial participation.
Abstract 12741: Prevention of Aneurysm Progression by a Peptide Vaccine Against Angiotensin II in a Rat Model
Authors: Tomohiro Kurashiki, Takashi Miyake, Hironori Nakagami, Motonobu Nishimura, Ryuichi Morishita
Journal: Circulation (2019)

Abdominal aortic aneurysm (AAA) is a common degenerative condition with high mortality in elderly individuals. However, there is no proven medical therapy to inhibit AAA progression in the clinical...
3D alveolar in vitro model based on epithelialized biomimetically curved culture membranes
Authors: D. Baptista, L. Moreira Teixeira, Z. Tahmasebi Birgani, S. van Riet, T. Pasman, A. Poot, D. Stamatialis, R.J. Rottier, P.S. Hiemstra, P. Habibović, C. van Blitterswijk, S. Giselbrecht, R. Truckenmüller
Journal: Biomaterials (2020)

There is increasing evidence that surface curvature at a near-cell-scale influences cell behaviour. Epithelial or endothelial cells lining small acinar or tubular body lumens, as those of the alveoli or blood vessels, experience such highly curved surfaces. In contrast, the most commonly used culture substrates for in vitro modelling of these human tissue barriers, ion track-etched membranes, offer only flat surfaces. Here, we propose a more realistic culture environment for alveolar cells based on biomimetically curved track-etched membranes, preserving the mainly spherical geometry of the cells' native microenvironment. The curved membranes were created by a combination of three-dimensional (3D) micro film (thermo)forming and ion track technology. We could successfully demonstrate the formation, the growth and a first characterization of confluent layers of lung epithelial cell lines and primary alveolar epithelial cells on membranes shaped into an array of hemispherical microwells. Besides their application in submerged culture, we could also demonstrate the compatibility of the bioinspired membranes for air-exposed culture. We observed a distinct cellular response to membrane curvature. Cells (or cell layers) on the curved membranes reveal significant differences compared to cells on flat membranes concerning membrane epithelialization, areal cell density of the formed epithelial layers, their cross-sectional morphology, and proliferation and apoptosis rates, and the same tight barrier function as on the flat membranes. The presented 3D membrane technology might pave the way for more predictive barrier in vitro models in future.
Balancing Risks in the Time of COVID-19
Authors: David W. Kimberlin, Karen M. Puopolo
Journal: JAMA Pediatrics (2020)

Dani Dumitriu, MD, PhD; Ukachi N. Emeruwa, MD, MPH; Erin Hanft, MD; Grace V. Liao, MD; Elizabeth Ludwig, MD; Lauren Walzer, DO; Brittany Arditi, MD, MSCR; Minna Saslaw, MD; Maria Andrikopoulou, MD, PhD; Tessa Scripps, MD; Caitlin Baptiste, MD; Adrita Khan, MD; Noelle Breslin, MD; David Rubenstein, MD; Lynn L. Simpson, MD; Margaret H. Kyle, BA; Alexander M. Friedman, MD, MPH; Daniel S. Hirsch, MD; Russell S. Miller, MD; Cristina R. Fernández, MD, MPH; Karin M. Fuchs, MD, MHA; M. Kathleen Keown, MD; Melissa E. Glassman, MD, MPH, IBCLC; Ashley Stephens, MD; Archana Gupta, MD; Sally Sultan, MD; Caroline Sibblies, MD; Susan Whittier, PhD; Wanda Abreu, MD, IBCLC; Francis Akita, MD; Anna Penn, MD, PhD; Mary E. D'Alton, MD; Jordan S. Orange, MD, PhD; Dena Goffman, MD; Lisa Saiman, MD, MPH; Melissa S. Stockwell, MD, MPH; Cynthia Gyamfi-Bannerman, MD, MSc
Concordance of MRI-guided and systematic prostate biopsy for the detection of prostate cancer (PCa).
Authors: Matthew Parsons, Bridget Foy, Ernest Chan, Bryan Crawford, Daniel Sommers, Jay Bishoff, Steven C Lynch, Benjamin Romney, David Michael Gill, Logan McLean
Journal: Journal of Clinical Oncology (2020)

277 Background: MRI/US guided biopsy (fusion biopsy) is increasingly utilized over systemic 12-core transrectal ultrasound biopsy (12-core biopsy) for men with MRI-visible prostate lesions. Methods: Patients with MRI visible prostate lesions who underwent fusion and 12-core biopsy from 2016-2020 in the Intermountain Healthcare (IHC) system were consecutively analyzed. This was in the setting of a continuous quality assurance initiative among the reading radiologists. Primary outcome was PCa detection defined by Gleason grade group (GGG) 1 or higher. Clinically significant cancer (CSC) was defined as GGG 2 or higher. Patients were stratified by date biopsy was performed, 2016-2017 and 2018-2020, and lesions were stratified by PI-RADS v2 category. For men with multiple lesions, the highest PI-RADS v2 category lesion was used. Results: A total of 142 men with 254 MRI-detectable lesions underwent both fusion and 12-core biopsies in the IHC system from 2016 to 2020. CSC was detected in 21.6% (55/254) of fusion biopsies. Comparing PI-RAD v2 categories 1-3 to PI-RADS v2 categories 4-5, the PPV for detecting CSC was 9% (15/162) compared to 44% (40/92) respectively. Fusion and 12-core biopsies were concordant for any PCa in 79% of men (112/142) and CSC in 83% (118/142). Fusion biopsy detected any PCa in 22/84 (26%) and CSC in 15/103 (15%) of men in whom 12-core biopsy was negative. 12-core biopsy detected any PCa in 8/70 (11%) and CSC in 9/97 (9%) of men in whom fusion was negative. In total, 15 patients (11%) had a CSC that would have been missed if fusion biopsy was omitted while 9 (6%) had a CSC that would have been missed without 12-core biopsy. Conclusions: Omitting fusion or 12-core biopsy for PI-RADS v2 lesions would have resulted in a missed CSC in 11% or 6% of patients from 2016-20, respectively. The combination of MRI/US-guided fusion biopsy and systematic 12-core biopsy increased detection rate of CSC. These results are in the setting of a continuous, multi-disciplinary quality assurance program and results are not necessarily applicable to other healthcare systems. [Table: see text]
A Cryptic BCR-PDGFRB Fusion Resulting in a Chronic Myeloid Neoplasm With Monocytosis and Eosinophilia: A Novel Finding With Treatment Implications
Authors: Sanjeev Kumar Gupta, Nitin Jain, Guilin Tang, Andrew Futreal, Sa A. Wang, Joseph D. Khoury, Richard K. Yang, Hong Fang, Keyur P. Patel, Rajyalakshmi Luthra, Mark Routbort, Bedia A. Barkoh, Wei Chen, Xizeng Mao, Jianhua Zhang, L. Jeffrey Medeiros, Carlos E. Bueso-Ramos, Sanam Loghavi
Journal: Journal of the National Comprehensive Cancer Network (2020)

RNA-seq was used to identify the partner gene and confirm the presence of a BCR-PDGFRB fusion. Identification of this fusion product resulted in successful treatment and long-term remission of this myeloid neoplasm. Based on our results, we suggest that despite current WHO recommendations, screening for PDGFRB rearrangement in cases of leukocytosis with eosinophilia and no other etiologic explanation is necessary, even if the karyotype is normal.
Understanding 'Non-genetic' Inheritance: Insights from Molecular-Evolutionary Crosstalk
Authors: Irene Adrian-Kalchhauser, Sonia E. Sultan, Lisa N.S. Shama, Helen Spence-Jones, Stefano Tiso, Claudia Isabelle Keller Valsecchi, Franz J. Weissing
Journal: Trends in Ecology & Evolution (2020)

Understanding the evolutionary and ecological roles of 'non-genetic' inheritance (NGI) is daunting due to the complexity and diversity of epigenetic mechanisms. We draw on insights from molecular and evolutionary biology perspectives to identify three general features of 'non-genetic' inheritance systems: (i) they are functionally interdependent with, rather than separate from, DNA sequence; (ii) precise mechanisms vary phylogenetically and operationally; and (iii) epigenetic elements are probabilistic, interactive regulatory factors and not deterministic 'epialleles' with defined genomic locations and effects. We discuss each of these features and offer recommendations for future empirical and theoretical research that implements a unifying inherited gene regulation (IGR) approach to studies of 'non-genetic' inheritance.
Evaluation and Treatment of Patients With Hypercortisolism
Authors: Barbra S. Miller, Richard J. Auchus
Journal: JAMA Surgery (2020)

<h3>Importance</h3> With the potential for severe adverse effects of hypercortisolism, the need to limit the development and unrecognized persistence of sequelae from cortisol excess is of great importance on individual and population health levels. This review discusses the evaluation and treatment of patients with hypercortisolism. Pathophysiology; pitfalls in the diagnosis of hypercortisolism; and preoperative, perioperative, and postoperative management considerations are discussed. The association of hypercortisolism with population health and the potential role surgeons and surgery can play in the future of patients with hypercortisolism are also discussed. Higher-level considerations are put forth to encourage a long-term view of future work needed to optimally care for these patients. <h3>Observations</h3> Although classic signs and symptoms of hypercortisolism are evident in some patients, mild autonomous cortisol secretion is likely more prevalent and more difficult to detect despite having the potential to cause significant adverse effects, such as increased risk of mortality, and overt hypercortisolism. With treatment, some adverse effects of hypercortisolism may resolve, although not in all patients. Thus, the need for early diagnosis and treatment is of great importance. <h3>Conclusions and Relevance</h3> More attention in the future on early treatment of hypercortisolism, whether subclinical or overt, and prevention of adverse effects is warranted for the sake of the individual and the population.
Familial Mediterranean fever.
Authors: Caroline Vinit
Journal: BMJ (1968)

FAMILIAL MEDITERRANEAN FEVER. Familial mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease worldwide. The recurrence of stereotyped febrile attacks lasting less than 3 days, associated with acute abdominal pain and a biological inflammatory syndrome in a child from the Mediterranean area, should raise its diagnosis. The detection of mutations in MEVF gene (exon 10 mainly) confirms the diagnosis. Long-term treatment with colchicine prevents the occurrence of attacks, and the development of secondary amyloidosis in adulthood, the most severe complication. The pathophysiology is increasingly well understood, with a key role for interleukin 1 (IL1), allowing the emergence of specific targeting therapies. Thus, IL1-blocking agents are second-line treatments, restricted for the very limited cases of patients, with colchicine resistance or intolerance.
Caudal type homeoboxes as a driving force in <i>Helicobacter pylori</i> infection-induced gastric intestinal metaplasia
Authors: Hong-Yan Chen, Yi Hu, Nong-Hua Lu, Yin Zhu
Journal: Gut Microbes (2020)

Helicobacter pylori (H. pylori), a common pathogenic bacterium in the stomach, has been demonstrated to be a major cause of gastric cancer (GC). The typical pathological evolution of H. pylori infection-induced GC involves development from gastric atrophy, via intestinal metaplasia (IM) and dysplasia, to intestinal-type GC. During this process, IM is considered to be an "irreversible point" that significantly increases the risk for GC. Therefore, the elucidation of the mechanism underlying IM is of great significance for the prevention and treatment of gastric mucosal carcinogenesis associated with H. pylori infection. Caudal type homeoboxes (CDXs) are transcription factors involved in intestinal differentiation establishment and the maintenance of normal intestinal mucosa and IM. H. pylori infection increases the expression of CDXs through epigenetic regulation, the nuclear factor-kappaB signaling pathway and its downstream proinflammatory factors, and the transforming growth factor-beta signaling pathway, leading to the progression from normal gastric mucosa to IM. However, the precise mechanisms of gastric intestinal metaplasia have not yet been fully elucidated. In this review, we focus on research progress revealing the functions of CDXs in H. pylori infection-induced IM, as well as the regulators modulating this process.
Increasing non-opioid pain management in the cancer patient presenting to the emergency department.
Authors: Adriana Wechsler, Ngoc Vu
Journal: Journal of Clinical Oncology (2020)

237 Background: The opioid epidemic is claiming more than 115 lives daily in the US (1). Pain is commonly the chief complaint of cancer patients presenting to the emergency department (ED) and aggressively managed with opioids. A recent study of cancer patients presenting to the ED showed they were also at high risk for opioid misuse (2). Non-opioid analgesia is often avoided from concerns of masking fevers, intolerance due to nausea/vomiting, or bleeding risk in thrombocytopenia. Our aim was to identify opportunities to reduce opioid use while safely alleviating pain in patients presenting to the Emergency Department of a comprehensive cancer center. Methods: Following the PDSA model, baseline data on current opioid use was obtained and perceived barriers to non-opioid analgesia were identified through questionnaires. Comfort level with non-opioid analgesia in cancer patients and current pain management practice was also queried. Patients eligible for non-opioid analgesia (solid tumors, no fever, pain score &lt; 7) were then identified through retrospective chart review and the prevalence of contraindications for non-opioid (renal/liver failure, thrombocytopenia, oral intolerance) and patient preference for opioids was calculated. This data and opportunities to use non-opioid analgesia was shared with providers in education sessions. Medication order panels were modified to provide easy access to oral and intravenous acetaminophen (APAP) and nonsteroidal anti-inflammatory drugs (NSAIDs). After two months the change in opioid prescribing was calculated. Results: Providers self-reported barriers to prescribing opioids as: low platelets, patient preference, and poor oral intake. Of 237 patients presenting to the MDA Emergency Department with complaints of pain between January 2018 and May 2018, 76 (32%) were eligible for non-opioid analgesia. Only 3 patients had absolute contraindications to both APAP or NSAIDs. After provider education, order entry simplification and prescribing guidance, the use of non-opioid analgesia rose from 3.9% to 9.4%. Patient satisfaction with pain control rose from 57.4 to 60.4 % following the intervention based on Press Ganey results. Conclusions: There is opportunity for non-opioid acute pain management in the solid tumor patients. Contraindications to non-opioid analgesia are uncommon. In the emergency department, safe pain relief can be provided by non-opioids such as NSAIDs and APAP.
Revision procedure for stent extension in a sharply angulated gastroesophageal junction cancer using endoscopic countertraction
Authors: Vincent Zimmer
Journal: Endoscopy (2020)

A 95-year-old man with locally advanced gastroesophageal junction cancer diagnosed 2 months previously was referred for consideration of stent revision due to recurrent dysphagia. The patient had undergone stent treatment before, complicated by failure to advance a conventional applicator system through the short but tight and sharply angulated malignant stricture. Therefore, on that occasion, a 60- × 10-mm uncovered gastroduodenal through-the-scope (TTS) stent was placed.