tbuckley/cabot-search huggingface dataset:
P06.07 Germline mutation of SMARCE1 gene in a family with spinal meningiomas
Authors: L Giunti, B Rinaldi, V Serio, A Buccoliero, E Fiorentini, G Casati, A Iorio, A Marturano, L Genitori, I Sardi
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Meningioma is the most common benign primary intracranial tumor, arising from arachnoid cells of the meninges, but in 20% of cases displays aggressive behavior. Meningiomas are mainly sporadic and the familial forms are very rare. Meningioma account for a small subset (1–4%) of all pediatric brain tumors and may be associated with hereditary tumor predisposition syndrome caused by germline mutations of NF2, SMARCB1, SUFU, and SMARCE1 genes. MATERIAL AND METHODS We present a case of a 16-year-old girl with spinal clear cell meningiomas (CCMs) WHO II with a second spinal lesion identified during the follow-up. Considering the multiple lesions, we performed Whole Exome Sequencing (WES) on DNA from peripheral blood to search for an underlying CCMs tumor predisposition syndrome (#607174). RESULTS We identified a heterozygous frameshift variant c.439delA (p.Ser147fs) in SMARCE1, chromatin remodelling factor that acts as a tumor suppressor gene. Meningioma analysis by Sanger sequencing showed a loss of heterozygosity (LOH) of the wild-type allele. We identified the c.439delA in the constitutional DNA of the father and the sister but not in the mother. At the moment, the father is asymptomatic and the 14 years old sister showed two spinal lesions (meningiomas likely) at the first MRI. CONCLUSION We report a family study of hereditary tumor predisposition syndrome to CCMs with SMARCE1 mutation in which are present two asymptomatic carriers with different ages and gender. The asymptomatic carriers will undergo neurological examination and MRI of the brain and spine, according to a screening protocol. The incomplete penetrance phenomenon is known in SMARCE1-related families with CCMs and it is probably due to the interaction of SMARCE1 with yet unidentified genes.
Self-harm in children and adolescents by ethnic group: an observational cohort study from the Multicentre Study of Self-Harm in England
Authors: Bushra Farooq, Caroline Clements, Keith Hawton, Galit Geulayov, Deborah Casey, Keith Waters, Jennifer Ness, Anita Patel, Samantha Kelly, Ellen Townsend, Louis Appleby, Nav Kapur
Journal: The Lancet Child & Adolescent Health (2021)
Minimum Threshold of Bariatric Surgical Weight Loss for Initial Diabetes Remission
Authors: Douglas Barthold, Elizabeth Brouwer, Lee J. Barton, David E. Arterburn, Anirban Basu, Anita Courcoulas, Cecelia L. Crawford, Peter N. Fedorka, Heidi Fischer, Benjamin B. Kim, Edward C. Mun, Sameer B. Murali, Kristi Reynolds, Tae K. Yoon, Robert E. Zane, Karen J. Coleman
Journal: Diabetes Care (2021)

OBJECTIVE There are few studies testing the amount of weight loss necessary to achieve initial remission of type 2 diabetes mellitus (T2DM) following bariatric surgery and no published studies with use of weight loss to predict initial T2DM remission in sleeve gastrectomy (SG) patients. RESEARCH DESIGN AND METHODS With Cox proportional hazards models we examined the relationship between initial T2DM remission and percent total weight loss (%TWL) after bariatric surgery. Categories of %TWL were included in the model as time-varying covariates. RESULTS Of patients (N = 5,928), 73% were female; mean age was 49.8 ± 10.3 years and BMI 43.8 ± 6.92 kg/m2, and 57% had Roux-en-Y gastric bypass (RYGB). Over an average follow-up of 5.9 years, 71% of patients experienced initial remission of T2DM (mean time to remission 1.0 year). With 0–5% TWL used as the reference group in Cox proportional hazards models, patients were more likely to remit with each 5% increase in TWL until 20% TWL (hazard ratio range 1.97–2.92). When categories &amp;gt;25% TWL were examined, all patients had a likelihood of initial remission similar to that of 20–25% TWL. Patients who achieved &amp;gt;20% TWL were more likely to achieve initial T2DM remission than patients with 0–5% TWL, even if they were using insulin at the time of surgery. CONCLUSIONS Weight loss after bariatric surgery is strongly associated with initial T2DM remission; however, above a threshold of 20% TWL, rates of initial T2DM remission did not increase substantially. Achieving this threshold is also associated with initial remission even in patients who traditionally experience lower rates of remission, such as patients taking insulin.
Preventing 30-day readmissions for patients with cancer: A root-cause analysis.
Authors: Manan P Shah, Irena Tan, Sarah K. Garrigues, Jennifer Hansen, Douglas W. Blayney, Vasu Divi
Journal: Journal of Clinical Oncology (2021)

226 Background: The high rate of unplanned 30-day readmissions for patients with cancer is a significant driver of costs and a marker of poor quality. In this study, we analyzed 30-day readmissions at our cancer center to determine causality and propose key drivers to prevent them. Methods: Patients with known cancer who were readmitted to our academic medical center within 30 days of a previous hospitalization were identified in our electronic health record by a third-party algorithm. Among patients with hematologic malignancies, only those undergoing bone marrow transplant care were included. Surveys querying causality and preventability of the readmissions were sent to the patients’ attending oncologists. Electronic chart documentation of readmissions were reviewed by two investigators to assess causality and preventability of each readmission. Results were discussed in focus groups to determine key drivers to prevent 30-day readmissions. Results: 437 readmissions were identified between 9/1/19 and 8/31/20, and 182 readmissions with corresponding surveys completed by their oncologists were identified (Table). Based on survey responses, 30 (16%) of the 182 readmissions were preventable, whereas based on our review, 56 (31%) were preventable. The top three causes of the 56 preventable readmissions were: underutilized ambulatory care (43%), premature discharge (23%), and goals of care discordance (16%). For underutilized ambulatory care, the primary treatments provided during those readmissions were: procedures such as thoracentesis and paracentesis (42%), medication administration for pain or nausea (33%), and infusions or transfusions (25%). Notably, most of these patients either did not attempt to seek outpatient care (42%) or were not able to secure an ambulatory appointment (29%) prior to their readmission. Through focus group discussions, we found that the key drivers to reduce preventable 30-day readmissions at our institution are (1) timely access to outpatient pleural effusion and ascites management, (2) timely access to ambulatory management of cancer-related symptoms (e.g., pain, nausea, weakness), (3) increased systems-wide awareness and utility of avenues of urgent care, and (4) increased palliative care efforts in patients with readmissions. Conclusions: Systematic review of 30-day readmissions revealed a greater than anticipated portion of preventable readmissions. Root-cause analysis yielded key drivers to reduce 30-day readmissions at our cancer center.[Table: see text]
Myc determines the functional age state of oligodendrocyte progenitor cells
Authors: Björn Neumann, Michael Segel, Tanay Ghosh, Chao Zhao, Panagiotis Tourlomousis, Adam Young, Sarah Förster, Amar Sharma, Civia Zi-Yu Chen, Juan F. Cubillos, Khalil S. Rawji, Kevin J. Chalut, Robin J. M. Franklin
Journal: Nature Aging (2021)
Value and use of patient reported outcomes in sarcoma clinic through GetWell Loop app.
Authors: Ensi Voshtina, John A. Charlson
Journal: Journal of Clinical Oncology (2021)

179 Background: Symptom monitoring in cancer care through patient reported outcomes has been used as an approach to improve symptom detection and communication. Through monitoring of patient symptoms via a systematic way, previous studies have shown a reduction in ED visits and hospital admissions, an enhancement in patient-clinician communication and overall patient satisfaction and wellbeing. In this study, we evaluated outcomes of patient reported data by using the GetWell Loop app to help determine if it facilitates cancer care and improves clinical outcomes. Methods: We performed a retrospective, single-center analysis of sarcoma patients age &gt; 18 who between December 2019 to January 2021 received systemic treatment and were enrolled to use GetWell Loop app to report their treatment related outcomes. We asked patients how they are feeling on a systematic basis post treatment by using a series of questions related to their therapy and potential symptoms. Through the use of GetWell Loop, patients are able to record symptoms information and prompt evaluation by a healthcare provider if they report severe or rapidly changing symptoms. Descriptive statistics were used to summarize use of the GetWell Loop through patient surveys, app generated data, and data available in EPIC electronic medical record. We noted the number of yellow (moderate) and red (severe) alerts generated by patient responses and the corresponding alert trigger to health care provider response. Healthcare provider communication and interventions were recorded, as were hospitalizations and ED visits while using the app. Results: A total of 75 patients were invited to join enrollment. Of those, 54 activated the app, with an activation rate of 72%. Engagement rate was 61% and 74 total alerts were generated. Of the severity of symptoms leading to an alert, 28% were red alters and 72% were yellow alerts. Red alerts most commonly comprised of decreased fluid intake, constipation, and fevers. The majority of red alert symptoms lead to an intervention from nursing staff that started with a phone call, while a minority of interventions were in app messages with the patient. Five red alerts led to an ED visit. The majority of yellow alert symptoms were addressed through in app messages. Both clinical staff and patients felt it helped them stay connected. Patients were most adherent with the first treatment. Patient satisfaction was 87.5% with the app usage. Conclusions: Using patient reported outcomes by using the GetWell Loop app yielded an overall positive patient experience. It provides an opportunity to intervene early with high risk patients and prevent ED visits. Focusing on the first cycle of a regiment and subsequent cycles if high risk seemed to provide the most benefit. There is utility to expand to other disease teams and use the app for survivorship support as well.
Increased fidelity of protein synthesis extends lifespan
Authors: Victoria Eugenia Martinez-Miguel, Celia Lujan, Tristan Espie--Caullet, Daniel Martinez-Martinez, Saul Moore, Cassandra Backes, Suam Gonzalez, Evgeniy R. Galimov, André E.X. Brown, Mario Halic, Kazunori Tomita, Charalampos Rallis, Tobias von der Haar, Filipe Cabreiro, Ivana Bjedov
Journal: Cell Metabolism (2021)

Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life, in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies. These findings pave the way for identifying novel translation accuracy interventions to improve aging.
Radiofrequency ablation: time to think of poor responders
Authors: Barbara Braden
Journal: Endoscopy (2021)

Since its first description in 2004 by Ganz et al. [1], radiofrequency ablation (RFA) has become the standard treatment of flat dysplastic Barrett’s esophagus (BE) after endoscopic resection of all visible lesions. Compared with alternative eradication methods, such as stepwise endoscopic resection, (hybrid) argon plasma coagulation, and cryoablation, RFA is the best validated and most used ablation method that is both effective and relatively safe, and is unanimously recommended by various guidelines.
左室容積は,充満圧と,僧帽弁輪速度に対する流入速度の早期拡張比(E/e’)の間の関係に影響する
Authors: Nakabachi Masahiro, Yamada Satoshi, Iwano Hiroyuki, Hayashi Taichi, Okada Kazunori, Kusunose Kenya, Watanabe Kiyotaka, Ishizu Tomoko, Wakami Kazuaki, Yamada Hirotsugu, Dohi Kaoru, Seo Yoshihiro, Ohte Nobuyuki, Shimizu Chikara, Mikami Taisei
Journal: Circulation (2018)
The transcription factor zinc fingers and homeoboxes 2 alleviates NASH by transcriptional activation of phosphatase and tensin homolog
Authors: Yichao Zhao, Lingchen Gao, Chenglin Jiang, Jianqing Chen, Zihan Qin, Fangyuan Zhong, Yang Yan, Renyang Tong, Meng Zhou, Ancai Yuan, Jun Pu
Journal: Hepatology (2021)

Abstract Background and Aims NASH, which is a common clinical condition predisposing to advanced liver diseases, has become a worldwide epidemic. A large and growing unmet therapeutic need for this condition reflects incomplete understanding of its pathogenesis. In the current study, we identified a transcription factor, zinc fingers and homeoboxes 2 (ZHX2), in hepatocytes as a protective factor against steatohepatitis. Approach and Results We found that hepatic ZHX2 was significantly suppressed in NASH models and steatotic hepatic cells. Hepatocyte‐specific ablation of ZHX2 exacerbated NASH‐related phenotypes in mice, including lipid accumulation, enhanced inflammation, and hepatic fibrosis. Conversely, hepatocyte‐specific overexpression of ZHX2 significantly alleviated the progression of NASH in an experimental setting. Integrated analysis of transcriptomic profiling and chromatin immunoprecipitation sequencing data demonstrated that the phosphatase and tensin homolog (PTEN) was a target gene of ZHX2 in hepatocyte. ZHX2 bound to the promoter of PTEN gene and subsequently promoted the transcription of PTEN, which mediated the beneficial role of ZHX2 against NASH. Conclusions The current findings demonstrate a protective role of ZHX2 against NASH progression by transcriptionally activating PTEN. These findings shed light on the therapeutic potential of targeting ZHX2 for treating NASH and related metabolic disorders.
STAT: a fast, scalable, MinHash-based k-mer tool to assess Sequence Read Archive next-generation sequence submissions
Authors: Kenneth S. Katz, Oleg Shutov, Richard Lapoint, Michael Kimelman, J. Rodney Brister, Christopher O’Sullivan
Journal: Genome biology (2021)

Abstract Sequence Read Archive submissions to the National Center for Biotechnology Information often lack useful metadata, which limits the utility of these submissions. We describe the Sequence Taxonomic Analysis Tool (STAT), a scalable k- mer-based tool for fast assessment of taxonomic diversity intrinsic to submissions, independent of metadata. We show that our MinHash-based k- mer tool is accurate and scalable, offering reliable criteria for efficient selection of data for further analysis by the scientific community, at once validating submissions while also augmenting sample metadata with reliable, searchable, taxonomic terms.
Reliability of claims-based measures used to assess cancer care quality.
Authors: Benjamin Urick, Sabree Burbage, Christopher Baggett, Jennifer Elston Lafata, Hanna Kelly Sanoff, Justin G. Trogdon
Journal: Journal of Clinical Oncology (2021)

42 Background: As value-based payment models for cancer care expand, the need for measures which reliably assess the quality of care provided increases. This is especially true for models like the Oncology Care Model (OCM) that rely on quality rankings to determine potential shared savings. Under models like these, unreliable measures may result in arbitrary application of value-based payments. The goal of this project is to evaluate the extent to which measures used within the OCM are reliable indicators of provider performance. Methods: Data for this project came from North Carolina Medicare claims from 2015-2017. Episodes were attributed to physician practices at the tax identification number (TIN) level, lasted 6 months, and were divided into two performance years beginning 1/1/2016 and 7/1/2016. TINs with fewer than 20 attributed patients were excluded. Three claims-based OCM measures were used in this evaluation: 1) proportion of episodes with all-cause hospital admissions; 2) proportion of episodes with all-cause emergency department (ED) visits or observation stays; and 3) proportion of patients that died who were admitted to hospice for 3 days or more. Risk adjustment followed the method described by measure specifications from the OCM. Reliability was calculated as the ratio of between practice variation (e.g. signal) to the sum of between practice variation and within practice variation (e.g. noise). Variance estimates were derived from hierarchical logistic regression models used for risk adjustment. Results: For the hospitalization and ED visit measures, episode counts for years 1 and 2 were 30,746 and 28,430 and TIN counts were 86 and 84, respectively. Hospice use measures had fewer episodes (2,677 and 2,428) and TINs (36 and 33). Across all measures, median reliability scores failed to achieve the recommended 0.7 threshold and only hospice had a median reliability score above 0.5 (Table). Conclusions: These findings suggest claims-based measures included in the OCM may produce imprecise estimates of provider performance and are vulnerable to random variation. Consideration should be given to developing alternative measures which may be more reliable estimates of provider performance and to increasing minimum denominator requirements for existing measures.[Table: see text]
Clathrin packets move in slow axonal transport and deliver functional payloads to synapses
Authors: Archan Ganguly, Rohan Sharma, Nicholas P. Boyer, Florian Wernert, Sébastien Phan, Daniela Boassa, Leonardo Parra, Utpal Das, Ghislaine Caillol, Xuemei Han, John R. Yates, Mark H. Ellisman, Christophe Leterrier, Subhojit Roy
Journal: Neuron (2021)
The value of pathways on drug costs.
Authors: Valerie Pracilio Csik, Michael J. Ramirez, Adam F Binder, Nathan Handley
Journal: Journal of Clinical Oncology (2021)

327 Background: Oncology care represents a significant portion of US healthcare spending. Cost of Part B drugs has increased at a rate 5.7x that of overall Medicare spending. As a participant in the Oncology Care Model, drug costs represent a majority of our total costs. Pathways are a clinical decision-support tool that use evidence-based care maps accounting for efficacy, toxicity and cost. Our NCI-designated cancer center implemented pathways in July 2018 to reduce care variation and decrease costs. Methods: We reviewed costs related to pathway utilization over a two year period, analyzing differences in total annual drug cost for patients in three categories: On-Pathway (aligned with pathway recommendation), Off-Pathway (not aligned with recommendation), and No Pathway (not used). Per Member Per Month (PMPM) costs were calculated and a weighted average applied to account for changes in annual drug costs. Results: PMPM drug costs decreased -8% in year 1 (FY19) and -4% in year 2 (FY20) when pathways were used (On- and Off-Pathway). When pathways were followed (On-Pathway) in making treatment decisions, the drug costs were 11% lower than when pathways were not used. The annual impact on drug costs when pathways were used amounted to $2.45 million in year 1 and $1.77 million in year 2 (Table). Conclusions: Pathway use reduced drug costs, a significant variable in oncology value-based care models. This finding highlights the value of clinical decision support tools in reducing care variability, a known contributor to health care costs, in making treatment decisions. Further assessment is needed to determine if these results are similar at other cancer centers to fully realize the impact of pathways on drug costs.[Table: see text]
The antimicrobial peptide S100A8/A9 produced by airway epithelium functions as a potent and direct regulator of macrophage phenotype and function
Authors: Wioletta Skronska-Wasek, Sibel Durlanik, Huy Quang Le, Victoria Schroeder, Kerstin Kitt, James Peter Garnett, Stefan Pflanz
Journal: European Respiratory Journal (2021)

Elevated counts of alveolar macrophages and attenuated phagocytic capacity are associated with chronic obstructive pulmonary disease (COPD). Factors governing macrophage phagocytosis are poorly understood. In this study we aimed to compare the influence of airway epithelial cell secretions from individuals with COPD and without COPD (non-COPD) on macrophage phagocytic activity, and the role of antimicrobial peptides (AMPs).Supernatants from non-COPD and COPD small airway epithelial cell (SAEC) cultures exposed to non-typeable Haemophilus influenzae (NTHi) were applied to human monocyte-derived macrophages (MDMs) to assess their influence on phagocytosis. SAECs were analysed for changes in AMP expression by quantitative reverse transcription PCR, and the influence of select AMPs on macrophage phenotype and function was assessed by flow cytometry and metabolic activity assay.Secretions from the apical and basolateral surface of NTHi-exposed SAECs from non-COPD donors elicited superior phagocytic capacity in MDMs. Moreover, NTHi exposure led to a rapid increase in the expression of a range of AMPs by non-COPD SAECs, but this response was delayed in COPD SAECs. We demonstrate that treatment with AMPs β-defensin 2 and S100 calcium binding protein A8/S100 calcium binding protein A9 (S100A8/A9) improved the phagocytic capacity of MDMs. In-depth analysis of the influence of S100A8/A9 on MDMs revealed a role for this AMP in macrophage phenotype and function. Furthermore, we show that the expression of S100A8 and S100A9 is directly regulated by WNT/β-catenin signalling, a known deregulated pathway in COPD.In conclusion, for the first time, we demonstrate that airway epithelium from patients with COPD has a reduced capacity to support the phagocytic function of macrophages in response to acute NTHi exposure, and we identify the WNT/β-catenin signalling-modulated and epithelium-derived S100A8/A9 as a potent regulator of macrophage phenotype and function.
Urinary Tract Infections in Children with Vesicoureteral Reflux Are Accompanied by Alterations in Urinary Microbiota and Metabolome Profiles
Authors: Dijana Vitko, Joseph W. McQuaid, Ali Hashemi Gheinani, Kohei Hasegawa, Shannon DiMartino, Kylie H. Davis, Candace Y. Chung, Joseph F. Petrosino, Rosalyn M. Adam, Jonathan M. Mansbach, Richard S. Lee
Journal: European Urology (2021)