tbuckley/cabot-search huggingface dataset:
Mouthguards should be worn in contact sports
Authors: Paul Allison, Faleh Tamimi
Journal: British Journal of Sports Medicine (2020)

In their well-designed, case–control investigation of mouthguard use in youth ice hockey players and the risk of concussion, Chisholm and colleagues1 report that those wearing a mouthguard—whether custom-made or off-the-shelf—had lower rates of concussion than control participants. The point estimate suggests a considerably reduced risk, although the CIs are broad. The authors report differences in the estimate of reduced risk for custom-made and off-the-shelf mouthguards, with the latter (perhaps surprisingly) having a greater reduction, although again the CIs are broad. The authors are explicit that their study is not powered for precise estimates of this secondary analysis, so we must all be cautious in interpreting this latter observation.

The primary observation—that mouthguards are associated with a lower rate of concussion—is an important contribution to the literature. The finding differs from that of the most recent systematic review of whether mouthguards can protect against concussion in contact sports, which concluded that ‘the effect of mouthguards on concussion risk was minimal’,2 although …
Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia
Authors: Tobias Herold, Maja Rothenberg-Thurley, Victoria V. Grunwald, Hanna Janke, Dennis Goerlich, Maria C. Sauerland, Nikola P. Konstandin, Annika Dufour, Stephanie Schneider, Michaela Neusser, Bianka Ksienzyk, Philipp A. Greif, Marion Subklewe, Andreas Faldum, Stefan K. Bohlander, Jan Braess, Bernhard Wörmann, Utz Krug, Wolfgang E. Berdel, Wolfgang Hiddemann, Karsten Spiekermann, Klaus H. Metzeler
Journal: Leukemia (2020)

Abstract The revised 2017 European LeukemiaNet (ELN) recommendations for genetic risk stratification of acute myeloid leukemia have been widely adopted, but have not yet been validated in large cohorts of AML patients. We studied 1116 newly diagnosed AML patients (age range, 18–86 years) who had received induction chemotherapy. Among 771 patients not selected by genetics, the ELN-2017 classification re-assigned 26.5% of patients into a more favorable or, more commonly, a more adverse-risk group compared with the ELN-2010 recommendations. Forty percent of the cohort, and 51% of patients ≥60 years, were classified as adverse-risk by ELN-2017. In 599 patients &lt;60 years, estimated 5-year overall survival (OS) was 64% for ELN-2017 favorable, 42% for intermediate-risk and 20% for adverse-risk patients. Among 517 patients aged ≥60 years, corresponding 5-year OS rates were 37, 16, and 6%. Patients with biallelic CEBPA mutations or inv(16) had particularly favorable outcomes, while patients with mutated TP53 and a complex karyotype had especially poor prognosis. DNMT3A mutations associated with inferior OS within each ELN-2017 risk group. Our results validate the prognostic significance of the revised ELN-2017 risk classification in AML patients receiving induction chemotherapy across a broad age range. Further refinement of the ELN-2017 risk classification is possible.
Pre-migration socioeconomic status and post-migration health satisfaction among Syrian refugees in Germany: A cross-sectional analysis
Authors: Jan Michael Bauer, Tilman Brand, Hajo Zeeb
Journal: PLoS Medicine (2020)

The large increase in numbers of refugees and asylum seekers in Germany and most of Europe has put the issue of migration itself, the integration of migrants, and also their health at the top of the political agenda. However, the dynamics of refugee health are not yet well understood. From a life-course perspective, migration experience is associated with various risks and changes, which might differ depending on the socioeconomic status (SES) of refugees in their home country. The aim of this paper was to analyze the relationship between pre-migration SES and self-reported health indicators after migration among Syrian refugees. Specifically, we wanted to find out how their SES affects the change in health satisfaction from pre- to post-migration.We used data from the 2016 refugee survey, which was part of the German Socio-Economic Panel (GSOEP). Although cross-sectional by design, this survey collected information referring to the current situation as a refugee in Germany as well as to their situation before migration. Using a sample of 2,209 adult Syrian refugees who had entered Germany between 2013 and 2016, we conducted a cross-sectional and a quasi-longitudinal (retrospective) analysis. The mean ± SD age was 35 ± 11 years, with 64% of the participants being male. Our results showed a positive association between pre-migration self-reported SES and several subjective health indicators (e.g., health satisfaction, self-reported health, mental health) in the cross-sectional analysis. However, the quasi-longitudinal analysis revealed that the socioeconomic gradient in health satisfaction before migration was strongly attenuated after migration (SES-by-time interaction: -0.48, 95% CI -0.61 to -0.35, p < 0.001; unstandardized regression coefficients, 5-point SES scale and 11-point health outcome scale). Similar results were produced after controlling for sociodemographic characteristics, experiences during the migration passage, and the current situation in Germany. A sex-stratified analysis showed that while there was some improvement in health satisfaction among men from the lowest SES over time, no improvement was found among women. A limitation of this study is that it considers only the first months or years after migration. Thus, we cannot preclude that the socioeconomic gradient regains importance in the longer run.Our findings suggest that the pre-migration socioeconomic gradient in health satisfaction is strongly attenuated in the first years after migration among Syrian refugees. Hence, a high SES before crisis and migration provides limited protection against the adverse health effects of migration passage.
Recent technological advancements in radiofrequency- andmicrowave-mediated hyperthermia for enhancing drug delivery
Authors: M.M. Paulides, H. Dobsicek Trefna, S. Curto, D.B. Rodrigues
Journal: Advanced Drug Delivery Reviews (2020)

Hyperthermia therapy is a potent enhancer of chemotherapy and radiotherapy. In particular, microwave (MW) and radiofrequency (RF) hyperthermia devices provide a variety of heating approaches that can treat most cancers regardless the size. This review introduces the physics of MW/RF hyperthermia, the current state-of-the-art systems for both localized and regional heating, and recent advancements in hyperthermia treatment guidance using real-time computational simulations and magnetic resonance thermometry. Clinical trials involving RF/MW hyperthermia as adjuvant for chemotherapy are also presented per anatomical site. These studies favor the use of adjuvant hyperthermia since it significantly improves curative and palliative clinical outcomes. The main challenge of hyperthermia is the distribution of state-of-the-art heating systems. Nevertheless, we anticipate that recent technology advances will expand the use of hyperthermia to chemotherapy centers for enhanced drug delivery. These new technologies hold great promise not only for (image-guided) perfusion modulation and sensitization for cytotoxic drugs, but also for local delivery of various compounds using thermosensitive liposomes.
Non-steroidal anti-inflammatory drugs and covid-19
Authors: Paul Little
Journal: BMJ (2020)

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RNF168-Mediated Ubiquitin Signaling Inhibits the Viability of <i>BRCA1</i>-Null Cancers
Authors: John J. Krais, Yifan Wang, Andrea J. Bernhardy, Emma Clausen, Jessica A. Miller, Kathy Q. Cai, Clare L. Scott, Neil Johnson
Journal: Cancer Research (2020)

Abstract BRCA1 gene mutations impair homologous recombination (HR) DNA repair, resulting in cellular senescence and embryonic lethality in mice. Therefore, BRCA1-deficient cancers require adaptations that prevent excessive genomic alterations from triggering cell death. RNF168-mediated ubiquitination of γH2AX at K13/15 (ub-H2AX) serves as a recruitment module for the localization of 53BP1 to DNA break sites. Here, we found multiple BRCA1-mutant cancer cell lines and primary tumors with low levels of RNF168 protein expression. Overexpression of ectopic RNF168 or a ub-H2AX fusion protein induced cell death and delayed BRCA1-mutant tumor formation. Cell death resulted from the recruitment of 53BP1 to DNA break sites and inhibition of DNA end resection. Strikingly, reintroduction of BRCA1 or 53BP1 depletion restored HR and rescued the ability of cells to maintain RNF168 and ub-H2AX overexpression. Thus, downregulation of RNF168 protein expression is a mechanism for providing BRCA1-null cancer cell lines with a residual level of HR that is essential for viability. Overall, our work identifies loss of RNF168 ubiquitin signaling as a proteomic alteration that supports BRCA1-mutant carcinogenesis. We propose that restoring RNF168-ub-H2AX signaling, potentially through inhibition of deubiquitinases, could represent a new therapeutic approach. Significance: This study explores the concept that homologous recombination DNA repair is not an all-or-nothing concept, but a spectrum, and that where a tumor stands on this spectrum may have therapeutic relevance. See related commentary by Wang and Wulf, p. 2720
Concerns Remain Regarding Long-term Ozone Exposure and Respiratory Outcomes—Reply
Authors: Laura M. Paulin, Joel D. Kaufman, Nadia N. Hansel
Journal: JAMA Internal Medicine (2020)

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Abstract P1-20-25: Impact of lumpectomy for diagnosis of primary tumor on disease free survival in women with operable breast cancer: An institutional audit
Authors: Nita Sukumar Nair, Rohini W Hawaldar, Quarratulain Chougle, Vani Parmar, Vaibhav Vanmali, Shabina Siddique, Ashwini Devade, Aarti Pandey, Shalaka Joshi, Sudeep Gupta, Rajendra A Badwe
Journal: Cancer Research (2020)

Abstract Introduction: As a tertiary referral cancer centre, 20-30 % of patients seen in our breast clinic present after excision of the primary breast tumour without oncological principles maintained and no details on the excision margins. We evaluated the safety of excision biopsy (ExBx) as a diagnostic procedure by comparing the outcomes against patients who underwent definitive surgery after a core biopsy/FNAC (CxBx) for diagnosis. Methods: We performed a retrospective audit of the case charts of women with breast cancer treated at our institution. We included women with operable breast cancer (OBC) who presented post ExBx of the primary tumour and those who were treatment naïve and operated after only a CxBx for diagnosis. Results: Of the 1022 women included in the analysis, 551 underwent ExBx for primary diagnosis and 471 had CxBx prior to definitive breast surgery. The excision biopsy group were younger women (median age 44 years) with smaller tumours (median T size 2.5cm), lower HR ( hormone receptor) positive (58.3%) and less number were Her2+ve (16.7 %). In this group 17% received NACT, with 66.4% undergoing breast conservation surgery (BCS), and 37.6% node positive. While in the core biopsy group, the women were older women (median age 50 years) had larger tumours, median 3 cm, with 71.3% HR positive, 18.3% Her2 +ve, 72.8% underwent breast conservation surgery with 44.6 % node positive At a median follow up of 46 months, there was no difference in four year disease free survival (DFS) between ExBx group (83.8% versus 86.8%) and non-ExBx (HR=1.29,95%CI=0.93-1.79, p=0.13). When matched for T size, 699/1022 (69%) had T2 tumours and DFS in ExBx group was 80.7% in compared to 85.7% in non ExBx group. (HR=1.46, 95%CI=1.0-2.11, p=0.04). On multivariate cox regression, T size (HR=1.45,95%CI=1.02-2.07, p=0.03), HR negative (HR=1.61,95%CI=1.15-2.26,p=0.006), node positivity (HR=1.82,95%CI=1.31-2.53,p&amp;lt;0.01) and ExBx done (HR=1.40,95%CI=0.99-1.98,p=0.053) had a detrimental impact on disease free survival. Conclusion: ExBx of the primary tumour as a diagnostic procedure not performed with oncological principles prior to definitive surgery has a detrimental impact on survival in women with operable breast cancer. Citation Format: Nita Sukumar Nair, Rohini W Hawaldar, Quarratulain Chougle, Vani Parmar, Vaibhav Vanmali, Shabina Siddique, Ashwini Devade, Aarti Pandey, Shalaka Joshi, Sudeep Gupta, Rajendra A Badwe. Impact of lumpectomy for diagnosis of primary tumor on disease free survival in women with operable breast cancer: An institutional audit [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-25.
Linear and circular PVT1 in hematological malignancies and immune response: two faces of the same coin
Authors: Martina Ghetti, Ivan Vannini, Clelia Tiziana Storlazzi, Giovanni Martinelli, Giorgia Simonetti
Journal: Molecular Cancer (2020)

Non coding RNAs (ncRNAs) have emerged as regulators of human carcinogenesis by affecting the expression of key tumor suppressor genes and oncogenes. They are divided into short and long ncRNAs, according to their length. Circular RNAs (circRNAs) are included in the second group and were recently discovered as being originated by back-splicing, joining either single or multiple exons, or exons with retained introns. The human Plasmacytoma Variant Translocation 1 (PVT1) gene maps on the long arm of chromosome 8 (8q24) and encodes for 52 ncRNAs variants, including 26 linear and 26 circular isoforms, and 6 microRNAs. PVT1 genomic locus is 54 Kb downstream to MYC and several interactions have been described among these two genes, including a feedback regulatory mechanism. MYC-independent functions of PVT1/circPVT1 have been also reported, especially in the regulation of immune responses. We here review and discuss the role of both PVT1 and circPVT1 in the hematopoietic system. No information is currently available concerning their transforming ability in hematopoietic cells. However, present literature supports their cooperation with a more aggressive and/or undifferentiated cell phenotype, thus contributing to cancer progression. PVT1/circPVT1 upregulation through genomic amplification or rearrangements and/or increased transcription, provides a proliferative advantage to malignant cells in acute myeloid leukemia, acute promyelocytic leukemia, Burkitt lymphoma, multiple myeloma (linear PVT1) and acute lymphoblastic leukemia (circPVT1). In addition, PVT1 and circPVT1 regulate immune responses: the overexpression of the linear form in myeloid derived suppressor cells induced immune tolerance in preclinical tumor models and circPVT1 showed immunosuppressive properties in myeloid and lymphoid cell subsets. Overall, these recent data on PVT1 and circPVT1 functions in hematological malignancies and immune responses reflect two faces of the same coin: involvement in cancer progression by promoting a more aggressive phenotype of malignant cells and negative regulation of the immune system as a novel potential therapy-resistance mechanism.
Multi-laboratory evaluation of ReaScan TBE IgM rapid test, 2016 to 2017
Authors: Bo Albinsson, Anu E. Jääskeläinen, Kairi Värv, Mateja Jelovšek, Corine GeurtsvanKessel, Sirkka Vene, Josef D. Järhult, Chantal Reusken, Irina Golovljova, Tatjana Avšič-Županc, Olli Vapalahti, Åke Lundkvist
Journal: Eurosurveillance (2020)

Background Tick-borne encephalitis (TBE) is a potentially severe neurological disease caused by TBE virus (TBEV). In Europe and Asia, TBEV infection has become a growing public health concern and requires fast and specific detection. Aim In this observational study, we evaluated a rapid TBE IgM test, ReaScan TBE, for usage in a clinical laboratory setting. Methods Patient sera found negative or positive for TBEV by serological and/or molecular methods in diagnostic laboratories of five European countries endemic for TBEV (Estonia, Finland, Slovenia, the Netherlands and Sweden) were used to assess the sensitivity and specificity of the test. The patients’ diagnoses were based on other commercial or quality assured in-house assays, i.e. each laboratory’s conventional routine methods. For specificity analysis, serum samples from patients with infections known to cause problems in serology were employed. These samples tested positive for e.g. Epstein–Barr virus, cytomegalovirus and Anaplasma phagocytophilum , or for flaviviruses other than TBEV, i.e. dengue, Japanese encephalitis, West Nile and Zika viruses. Samples from individuals vaccinated against flaviviruses other than TBEV were also included. Altogether, 172 serum samples from patients with acute TBE and 306 TBE IgM negative samples were analysed. Results Compared with each laboratory’s conventional methods, the tested assay had similar sensitivity and specificity (99.4% and 97.7%, respectively). Samples containing potentially interfering antibodies did not cause specificity problems. Conclusion Regarding diagnosis of acute TBEV infections, ReaScan TBE offers rapid and convenient complementary IgM detection. If used as a stand-alone, it can provide preliminary results in a laboratory or point of care setting.
Extent of lymphadenectomy and lymph node ratio - Impact on surgical outcome of perihilar cholangiocarcinoma
Authors: Manuel Jaklitsch, Ines Barros, Gael Nana, Mafalda Sobral, David Keane, Danielle Trinca, Joao Santos Coelho, Eduardo Barroso, Hugo Pinto Marques
Journal: International Journal of Surgery (2020)
Abstract ES5-2: Regional Management of the Axilla prior to Systemic Therapy
Authors: M Pilewskie
Journal: Cancer Research (2020)

Abstract There is growing interest in personalizing axillary management strategies based on anatomic staging and receptor profile to minimize surgical morbidity and maximize oncologic outcomes. Axillary treatment decision making has become increasing complex given the variation in indications for axillary lymph node dissection (ALND) among clinically node negative patients based on treatment strategy. Current techniques to minimize the likelihood of requiring an ALND include application of the ACOSOG Z011 or AMAROS data for women undergoing surgery first or use of neoadjuvant chemotherapy (NAC) in attempts to downstage microscopic nodal disease. Hormone receptor positive, HER2 negative tumors have low pathologic complete response rates to NAC and therefore have low rates of axillary downstaging with this approach. We have evaluated the likelihood of requiring an ALND by receptor profile for differing management strategies. Given the low response rates to NAC among women with hormone receptor positive, HER2- tumors, use of NAC for this subtype is associated with a threefold increase in the receipt of ALND compared to those treated with upfront breast conserving surgery. In this session I will review the current strategies to minimize the likelihood of requiring an ALND among clinically node negative patients found to have a positive sentinel lymph node including application of the ACOSOG Z0011 and AMAROS strategies. I will also review the impact of axillary imaging and/or a positive lymph node needle biopsy on axillary surgery outcomes among clinically node negative patients. Having an understanding of these differing options will aid in personalizing axillary management recommendations to safely minimize the likelihood of ALND and the resultant risk of lymphedema. Citation Format: M Pilewskie. Regional Management of the Axilla prior to Systemic Therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES5-2.
Ten things the hematologist wants you to know about CAR-T cells
Authors: Boris Böll, Marion Subklewe, Michael von Bergwelt-Baildon
Journal: Intensive Care Medicine (2020)

Chimeric antigen-receptor T cells, CAR-T cells, are genetically engineered T-cells, and after decades of development, CAR-T constructs are approved for selected relapsed and refractory (r/r) CD19-positive hematological malignancies and are currently being tested in cancer, infectious disease and autoimmunity [1].About onethird of CAR-T patients require ICU treatment [2,3].Here are ten things your hematologist wants you to know about CAR-T cells.