tbuckley/cabot-search huggingface dataset:
HBeAg induces liver sinusoidal endothelial cell activation to promote intrahepatic CD8 T cell immunity and HBV clearance
Authors: Xiaohong Xie, Jinzhuo Luo, Ruth Broering, Dan Zhu, Wenqing Zhou, Mengji Lu, Xin Zheng, Ulf Dittmer, Dongliang Yang, Jia Liu
Journal: Cellular and Molecular Immunology (2021)
Circumcision and Risk of Febrile Urinary Tract Infection in Boys with Posterior Urethral Valves: Result of the CIRCUP Randomized Trial
Authors: Luke Harper, T Blanc, M Peycelon, J L Michel, M D Leclair, S Garnier, V Flaum, A P Arnaud, T Merrot, E Dobremez, A Faure, L Fourcade, M L Poli-Merol, Y Chaussy, O Dunand, F Collin, L Huiart, C Ferdynus, F Sauvat
Journal: European Urology (2021)
Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells
Authors: Daniel A. Lichtenstein, Fiorella Schischlik, Lipei Shao, Seth M. Steinberg, Bonnie Yates, Hao-Wei Wang, Yanyu Wang, Jon Inglefield, Alina Dulau-Florea, Francesco Ceppi, Leandro C. Hermida, Kate Stringaris, Kim Dunham, Philip Homan, Parthav Jailwala, Justin Mirazee, Welles Robinson, Karen M. Chisholm, Constance Yuan, Maryalice Stetler-Stevenson, Amanda K. Ombrello, Jianjian Jin, Terry J. Fry, Naomi Taylor, Steven L. Highfill, Ping Jin, Rebecca A. Gardner, Haneen Shalabi, Eytan Ruppin, David F. Stroncek, Nirali N. Shah
Journal: Blood (2021)
P13.17 <i>CD95</i> gene silencing affects growth and invasiveness of glioma-initiating cells in a CD95L-independent manner
Authors: C Quijano-Rubio, M Weller
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND CD95 (Fas/APO-1) holds a dual role of potential relevance in tumor development. CD95-CD95 ligand (CD95L) signaling regulates apoptotic cell death in CD95-expressing cells, but non-apoptotic, tumor-promoting CD95-CD95L signaling has been likewise described. Therapeutic stimulation of apoptotic CD95 signaling is associated with major clinical side effects. However, inhibition of tumor-promoting CD95 signaling may represent a promising treatment strategy for human cancers where potential tumor-promoting CD95 functions include invasiveness and cancer cell stemness, including glioblastoma. MATERIAL AND METHODS In this study, CD95 and CD95L expression was characterized in human glioma-initiating cells (GIC) in vitro and in vivo. CD95 and CD95L gene knockout (KO) GIC were generated by means of CRISPR-Cas9 and the effects of gene silencing were evaluated by assessing growth, clonogenicity, invasiveness and tumorigenicity in nude mice. RESULTS CD95 expression and sensitivity to exogenous CD95L-induced apoptosis were confirmed in selected GIC in vitro. CD95L expression was not detected. Upon CD95 KO, all GIC acquired resistance to CD95L-induced apoptosis. Furthermore, despite the confirmed absence of CD95L expression in vitro, CD95 KO S-24 GIC revealed decreased cell growth, inferior sphere forming capacity and decreased invasiveness. These data suggested a CD95L-independent tumor-promoting role of CD95 in S-24 GIC. In vivo, however, CD95 KO did not prolong the survival of glioma-bearing mice. Analyses of further GIC models are ongoing. CONCLUSION These data demonstrate that, unlike CD95, CD95L is not expressed in cultured human GIC and that CD95-CD95L interactions are not required for tumor-promoting CD95 signaling. Although CD95 KO is detrimental for S-24 GIC in vitro, CD95 KO alone does not affect survival in S-24 human GIC xenograft-bearing mice.
WHO cuts air pollution limits to save millions of lives
Authors: Luke Taylor
Journal: BMJ (2021)

World Health Organization leaders have announced strict new air pollution targets in the hope of saving millions of lives each year.

The UN agency revised its Global Air Quality Guidelines for the first time since 2005 after five years of systematic review of more than 500 research papers. On the basis of this evidence it concluded that air pollution was harmful to health at lower concentrations and produced a wider range of damage than was previously thought.

Tedros Adhanom Ghebreyesus, WHO’s director general, told a virtual press conference attended by senior officials in Geneva, Copenhagen, and Bonn, “A substantial new body of evidence has accumulated, further demonstrating the degree to which air pollution affects all parts of the body, from the brain to a growing baby in a mother’s womb, at even lower concentrations than previously observed.”

Seven million deaths a year are attributed to air pollution, and hundreds of millions of years of healthy life are lost, WHO said, making it as …
Non-invasive diagnosis of deep vein thrombosis from ultrasound imaging with machine learning
Authors: Bernhard Kainz, Mattias P. Heinrich, Antonios Makropoulos, Jonas Oppenheimer, Ramin Mandegaran, Shrinivasan Sankar, Christopher Deane, Sven Mischkewitz, Fouad Al-Noor, Andrew C. Rawdin, Andreas Ruttloff, Matthew D. Stevenson, Peter Klein-Weigel, Nicola Curry
Journal: npj Digital Medicine (2021)

Deep vein thrombosis (DVT) is a blood clot most commonly found in the leg, which can lead to fatal pulmonary embolism (PE). Compression ultrasound of the legs is the diagnostic gold standard, leading to a definitive diagnosis. However, many patients with possible symptoms are not found to have a DVT, resulting in long referral waiting times for patients and a large clinical burden for specialists. Thus, diagnosis at the point of care by non-specialists is desired. We collect images in a pre-clinical study and investigate a deep learning approach for the automatic interpretation of compression ultrasound images. Our method provides guidance for free-hand ultrasound and aids non-specialists in detecting DVT. We train a deep learning algorithm on ultrasound videos from 255 volunteers and evaluate on a sample size of 53 prospectively enrolled patients from an NHS DVT diagnostic clinic and 30 prospectively enrolled patients from a German DVT clinic. Algorithmic DVT diagnosis performance results in a sensitivity within a 95% CI range of (0.82, 0.94), specificity of (0.70, 0.82), a positive predictive value of (0.65, 0.89), and a negative predictive value of (0.99, 1.00) when compared to the clinical gold standard. To assess the potential benefits of this technology in healthcare we evaluate the entire clinical DVT decision algorithm and provide cost analysis when integrating our approach into diagnostic pathways for DVT. Our approach is estimated to generate a positive net monetary benefit at costs up to £72 to £175 per software-supported examination, assuming a willingness to pay of £20,000/QALY.
Transcriptome-Wide Dynamics of m<b>6</b>A mRNA Methylation During Porcine Spermatogenesis
Authors: Zidong Liu, Xiaoxu Chen, Pengfei Zhang, Fuyuan Li, Lingkai Zhang, Xueliang Li, Tao Huang, Yi Zheng, Taiyong Yu, Tao Zhang, Wenxian Zeng, Hongzhao Lu, Yinghua Lv
Journal: Genomics Proteomics & Bioinformatics (2021)

Spermatogenesis is a continual process that occurs in the testes, in which diploid spermatogonial stem cells (SSCs) differentiate and generate haploid spermatozoa. This highly efficient and intricate process is orchestrated at multiple levels. N
Comparison of Routine Replacement With Clinically Indicated Replacement of Peripheral Intravenous Catheters
Authors: Niccolò Buetti, Mohamed Abbas, Didier Pittet, Marlieke E. A. de Kraker, Daniel Teixeira, Marie-Noëlle Chraiti, Valérie Sauvan, Julien Sauser, Stephan Harbarth, Walter Zingg
Journal: JAMA Internal Medicine (2021)

Peripheral intravenous catheters (PVCs) are the most frequently used indwelling devices in hospitals worldwide. Peripheral intravenous catheter bloodstream infections (PVC-BSIs) are rare, but severe and preventable, adverse events.To investigate the incidence of PVC-BSIs after changing the policy of routine PVC replacement every 96 hours to clinically indicated replacement.This institution-wide, observational cohort study evaluated all patients hospitalized at a large university-affiliated hospital with 10 sites in Western Switzerland with a PVC insertion between January 1, 2016, and February 29, 2020.Peripheral intravenous catheters were routinely replaced every 96 hours until March 31, 2018 (baseline period). Between April 1, 2018, and October 15, 2019, PVCs were replaced if clinically indicated (intervention period). From October 16, 2019, PVCs were again routinely replaced every 96 hours (reversion period).The PVC-BSI rates and PVC-BSI incidence rate ratios (IRRs) during each period.A total of 412 631 PVCs with documented catheter duration were included (164 331 patients; median [interquartile range] patient age, 51 [33-72] years; 88 928 [54.1%] female): 241 432 PVCs at baseline, 130 779 at intervention, and 40 420 at reversion. Eleven PVC-BSIs were observed during the baseline period, 46 during the intervention, and 4 during the reversion period. Although the monthly number of PVC-days remained stable during all study periods, the number of monthly inserted PVCs decreased during the intervention period. The number of PVCs still in place more than 4 or more than 7 days was higher during the intervention period compared with the baseline and reversion periods. A significantly increased IRR of PVC-BSIs was observed for the intervention period (IRR, 7.20; 95% CI, 3.65-14.22; P < .001) compared with baseline, whereas during the reversion period there was no significant increase (IRR, 1.35; 95% CI, 0.30 6.17; P = .69).The results of this cohort study using a large, prospective surveillance database suggest that replacement of PVCs only when clinically indicated may be associated with an increased risk of PVC-BSI compared with routine replacement. Even if PVC-associated BSI is a rare event, the use of PVCs in most patients makes this outcome relevant.
Piloting the REDUCE score to decrease acute care utilization.
Authors: Valerie Pracilio Csik, Michael Li, Lauren Waldman, Brooke Worster, Adam F Binder, Nathan Handley
Journal: Journal of Clinical Oncology (2021)

252 Background: Emergency department visits and hospitalizations are common in patients with cancer, with nearly three quarters of patients with advanced disease hospitalized at least once in the year after their diagnosis. Efforts to prospectively identify patients at highest risk for this acute care utilization (ACU) are needed. While many risk scoring systems have been developed for this purpose, few have been effectively integrated into clinical practice. We piloted a prospective risk assessment tool using a quality improvement framework. Methods: We utilized our previously published REDUCE score (Reducing ED Utilization in the Cancer Experience) to pilot clinical interventions to reduce ACU using PDSA cycles. Cycle 1 included a chart review and targeted outreach by a nurse navigator to high risk patients identified by REDUCE. Outreach resulted in communication of patient needs to the care team, which may or may not have resulted in additional interventions. Cycle 2 involved initial identification by REDUCE followed by further assessment with a distress screening. Those who were high risk and had high distress (score ≥4) were discussed by an interdisciplinary team (including supportive medicine physicians, social work, nurses, nurse practitioners) to determine an appropriate intervention. Results: Of the patients in Cycle 1 (N = 138), 26.1% had ACU after outreach by a nurse navigator, while in Cycle 2 (N = 169) 7.1% had ACU after the intervention determined by the interdisciplinary team. The average distress score among all patients in Cycle 2 was 6.0 and the REDUCE score was 2.87, while the subset of patients who experienced ACU had an average distress score of 6.4 and a REDUCE score of 3.22. Conclusions: The REDUCE score may be a valuable tool to assist in identifying patients at risk for ACU. We found that combining the risk score with a biopsychosocial screening tool and multidisciplinary team discussion may prove more valuable than the risk score alone, with Cycle 2 findings suggesting that there is a directional correlation between REDUCE score and distress screening results. More work is needed to understand the relative impact of the REDUCE score and the biopsychosocial screening and team discussion on decreasing ACU.
Mutations in the adenosine deaminase ADAR1 that prevent endogenous Z-RNA binding induce Aicardi-Goutières-syndrome-like encephalopathy
Authors: Taisuke Nakahama, Yuki Kato, Toshiharu Shibuya, Maal Inoue, Jung In Kim, Tuangtong Vongpipatana, Hiroyuki Todo, Yanfang Xing, Yukio Kawahara
Journal: Immunity (2021)
Evaluating agreement between bodies of evidence from randomised controlled trials and cohort studies in nutrition research: meta-epidemiological study
Authors: Lukas Schwingshackl, Sara Balduzzi, Jessica Beyerbach, Nils Bröckelmann, Sarah S Werner, Jasmin Zähringer, Blin Nagavci, Joerg J Meerpohl
Journal: BMJ (2021)

Abstract Objective To evaluate the agreement between diet-disease effect estimates of bodies of evidence from randomised controlled trials and those from cohort studies in nutrition research, and to investigate potential factors for disagreement. Design Meta-epidemiological study. Data sources Cochrane Database of Systematic Reviews, and Medline. Review methods Population, intervention or exposure, comparator, outcome (PI/ECO) elements from a body of evidence from cohort studies (BoE(CS)) were matched with corresponding elements of a body of evidence from randomised controlled trials (BoE(RCT)). Pooled ratio of risk ratios or difference of mean differences across all diet-disease outcome pairs were calculated. Subgroup analyses were conducted to explore factors for disagreement. Heterogeneity was assessed through I 2 and τ 2 . Prediction intervals were calculated to assess the range of possible values for the difference in the results between evidence from randomised controlled trials and evidence from cohort studies in future comparisons. Results 97 diet-disease outcome pairs (that is, matched BoE(RCT) and BoE(CS)) were identified overall. For binary outcomes, the pooled ratio of risk ratios comparing estimates from BoE(RCT) with BoE(CS) was 1.09 (95% confidence interval 1.04 to 1.14; I 2 =68%; τ 2 =0.021; 95% prediction interval 0.81 to 1.46). The prediction interval indicated that the difference could be much more substantial, in either direction. We further explored heterogeneity and found that PI/ECO dissimilarities, especially for the comparisons of dietary supplements in randomised controlled trials and nutrient status in cohort studies, explained most of the differences. When the type of intake or exposure between both types of evidence was identical, the estimates were similar. For continuous outcomes, small differences were observed between randomised controlled trials and cohort studies. Conclusion On average, the difference in pooled results between estimates from BoE(RCT) and BoE(CS) was small. But wide prediction intervals and some substantial statistical heterogeneity in cohort studies indicate that important differences or potential bias in individual comparisons or studies cannot be excluded. Observed differences were mainly driven by dissimilarities in population, intervention or exposure, comparator, and outcome. These findings could help researchers further understand the integration of such evidence into prospective nutrition evidence syntheses and improve evidence based dietary guidelines.
Home-monitoring reduces hospital stay for COVID-19 patients
Authors: Laura Agnes Grutters, Kalle Iskander Majoor, Eline Solange Kirsty Pol-Mattern, Johannes Anthonie Hardeman, Christiaan Franciscus Pieter van Swol, Adriane Dore Marie Vorselaars
Journal: European Respiratory Journal (2021)

With great interest we read the article by Dirikgil et al . [1], in which they demonstrate the potential of home monitoring to reduce hospital admissions by safely surveying clinical symptoms and vital parameters. They encourage the further consideration of strategies for home monitoring larger patient groups and, particularly, patients with confirmed coronavirus disease 2019 (COVID-19). Home monitoring reduces hospital stay of patients with COVID-19, which increases regular healthcare capacity <https://bit.ly/3CdFp1z> We would like to thank F. de Winter and the home monitoring team of the St Antonius Hospital for their commitment to this study.
P03.05 The use of subcortical intraoperative electrical stimulation mapping for assessment of executive functions: A summary of the evidence so far
Authors: M J F Landers, M M Sitskoorn, G J M Rutten, E Mandonnet, W De Baene
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Over the past years, the functional subcortical architecture of the brain has been increasingly acknowledged in neurosurgical planning. A method to study anatomo-functional correlations is direct electrical stimulation (DES). DES is widely used by neurosurgeons and considered as a reliable tool to minimize the occurrence of permanent postoperative motor, language and visual deficits. In recent years, DES has also been used for mapping of other cognitive functions, such as executive functions. MATERIAL AND METHODS We systematically summarized the evidence so far from DES studies on subcortical pathways that are involved in the following three executive functions: (1) inhibitory control, (2) working memory and (3) cognitive flexibility. RESULTS We only found twelve articles that reported on intraoperative electrical stimulation of white matter pathways to map executive functions and explicitly clarified which subcortical tract was stimulated. The results indicate that the second branch of the right superior longitudinal fasciculus (SLF-II) is involved in inhibitory control, the first branch of the right superior longitudinal fasciculus (SLF-I) and the third branch of the left superior longitudinal fasciculus (SLF-III) are involved in working memory and the cingulum is involved in cognitive flexibility. CONCLUSION We were unable to draw any specific conclusions, nor unequivocally established the pathways involved in executive functions due to heterogenous study characteristics, methods and tasks, and the limited number of studies that assessed these relationships. Clearly, neurosurgical groups are exploring novel methods to assess cognition during awake neurosurgery, but are far from consensus on indications and protocols, which complicated the comparison and summarization of findings. We will discuss possible approaches for future research to obtain converging and more definite evidence for the involvement of subcortical pathways in specific executive functions.
P06.02 Efficacy of Arc based Radiation in children &amp; young adults with Medulloblastoma
Authors: S M Mathew, A S U, C V V, V Lokesh
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND To compare doses to Organs At Risk and assess low dose radiation bath by Cranio Spinal Irradiation in children and young adults with Medulloblastoma between different Techniques. MATERIAL AND METHODS 30 Patients [Median Age: 8(5–23), M: F= 2:1] with Medulloblastoma, planned for Craniospinal Irradiation by Arc based Radiotherapy (VMAT- Elekta) also had an alternative Radiotherapy Plan (IMRT/ 3DCRT) to compare radiation doses to critical OARs (Cochlea, Thyroid, Heart) and low dose radiation bath to Vertebral Body and Supratentorial normal brain). Mean doses of Organs in parallel, Maximum doses of organs in series and Integral Dose was compared. Pre radiation Vertebral Body CT Density (HU) and the absorbed dose to it at various levels was estimated for each patient on the TPS. With the PTV coverage being 95% to the volume, dosimetrically superior plan was chosen for therapy. RESULTS The cohort had a risk stratum in the ratio 4:1 (Standard: High). IHC based molecular subtyping showed WNT, SHH and Non WNT/ Non SHH sub type (3:1:2). For ease of Analysis, the sample was divided among age groups into &amp;lt;8 years, 8–12 years and &amp;gt;12 years. Among the various Age groups, children &amp;lt; 8 years received the lowest dose of 21 Gy to Thyroid via Arc Therapy [(27Gy±4Gy) vs (31Gy± 3Gy)]. Children at 8–12 years received the lowest mean dose of 35 Gy with Arc plan to B/L Cochlea. [(36Gy± 4Gy) vs 41Gy± 4 Gy)]. Significant reduction of Mean dose to the heart was noted in &amp;gt;12 years with Arc [(8 Gy± 1Gy) vs(10 Gy± 2 Gy)]. The Mean CT density by HU of Vertebral Body (Thoraco-Lumbar) estimated were 145 HU, 195 HU and 315 HU in three age groups. Mean Doses to the Vertebrae was significantly lower with VMAT in kids &amp;lt; 8 years. ([3211 cGy ± 80 cGy] vs [3397 cGy ± 70cGy]). Supratentorial brain (basi frontal) received an additional [373.9 cGy ± 0.2Gy] vs[425 cGy ±0.3 Gy]) during PF Boost. CONCLUSION Arc Therapy in Medulloblastoma reduces in field normal tissue radiation dose (Thyroid, Cochlea and heart) at respective ages of &amp;lt;8 years, 8–12 years and &amp;gt; 12 years as well as the low dose radiation bath to structures (Vertebral body and Supratentorial brain) beyond the target volume which may reduce long term complications in children and young adults.
Super-enhancer landscape reveals leukemia stem cell reliance on X-box binding protein 1 as a therapeutic vulnerability
Authors: Jingfeng Zhou, Shubo Wang, Danian Nie, Peilong Lai, Yiqing Li, Yangqiu Li, Yanli Jin, Jingxuan Pan
Journal: Science Translational Medicine (2021)

Leukemia stem cells are dependent on the super-enhancer–associated oncogene XBP1, suggesting a potential targeting strategy in relapsed CML.
P14.36 Characterising Meningiomas in young patients under 40
Authors: M Attia, Y Mirkin, R Hershkovitch, Z R Cohen, Z Zibly, J Zauberman, A Wohl, S Harnof, R Spiegelmann, M Hadani, O Furman, L Zach
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Meningiomas are the most common primary CNS tumor in adults, with a median age at diagnosis of 65 years and a female to male ratio of 2–3:1 (except in grade II, III meningiomas). Younger patients usually have a genetic background or history of prior radiation exposure. Based on population-level studies, approximately 80–85% of meningiomas are WHO grade I (benign), 15–18% grade II (atypical), and 1–3% grade III (anaplastic). This case series describes a single center experience of the presentation and pathology of meningiomas in patients under the age of 40. MATERIALS AND METHODS We reviewed the Sheba Medical Center Neurosurgery and radiotherapy databases containing patients who were operated on for meningioma between the years 2011–2020. Patients under 40 were selected and information from digital medical records was gathered on these patients, including pathology reports, surgical reports, clinical and radiological data, and the use of radiotherapy or medical treatments. RESULTS Of 600 patients in the database, 49 patients under 40 (8.3%) were identified and 54 tumors were reviewed (five patients were operated on for multiple meningiomas). 31 patients were female (63%); 2 were under 20 years old, 15 were age 20–29 and 32 were age 30–39 at first presentation. Seven patients had received prior radiation therapy for a childhood malignancy. 28 meningiomas were histology confirmed grade I (52%), 22 were grade II (41%), 2 were grade III (4%), and 2 (4%) were grade undetermined. 22 tumors were located in the skull base (41%) and 32 (59%) in the brain convexity. Of the skull base tumors, 16 were grade I, 5 were grade II, and one was grade III. Of the convexity tumors, 12 were grade I, 16 were grade II, and 2 were grade III. Median follow-up was 35 months, and longest follow-up time was 98 months. Six patients were treated with additional radiotherapy after surgery. CONCLUSION Our experience with meningioma patients under 40 revealed a different grade segregation than the older population, with younger patients showing a higher incidence of grade II tumors. These tumors are generally more aggressive, and require careful resection and consideration for post-surgical radiotherapy. Further validation with population based databases is required.