tbuckley/cabot-search huggingface dataset:
Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion
Authors: Zhixiong Cai, Xiaoping Su, Liman Qiu, Zhenli Li, Xiaolou Li, Xiuqing Dong, Fuqun Wei, Yang Zhou, Liuping Luo, Geng Chen, Hengkai Chen, Yingchao Wang, Yongyi Zeng, Xiaolong Liu
Journal: Molecular Cancer (2021)

Abstract Background Clinically, prophylactic anti-recurrence treatments for hepatocellular carcinoma (HCC) patients after radical surgery are extremely limited. Neoantigen based vaccine can generate robust anti-tumor immune response in several solid tumors but whether it could induce anti-tumor immune response in HCC and serve as a safe and effective prophylactic strategy for preventing postoperative HCC recurrence still remain largely unclear. Methods Personalized neoantigen vaccine was designed and immunized for 10 HCC patients with high risk of postoperative recurrence in a prime-boost schedule. The safety and immune response were assessed through adverse events, tissue sequencing, ELISpot, TCR sequencing. The clinical response was evaluated by recurrence-free survival (RFS) and personalized circulating tumor DNA (ctDNA) sequencing. Results In the 10 enrolled patients, no obvious adverse events were observed during neoantigen vaccinations. Until the deadline of clinical trial, 8 of 10 patients were confirmed with clinical relapse by imaging, the other 2 patients remained relapse-free. From receiving first neoantigen vaccination, the median RFS of 10 patients were 7.4 months. Among 7 patients received all planned neoantigen vaccinations, 5 of them demonstrated neoantigen-induced T cell responses and have significantly longer RFS after radical surgery than other 5 patients without responsive neoantigens or only with prime vaccination and propensity scores matching control patients ( p = 0.035). Moreover, tracking personalized neoantigen mutations in ctDNA could provide real-time evaluation of clinical response in HCC patients during neoantigen vaccination and follow up. Conclusion Personalized neoantigen vaccine is proved as a safe, feasible and effective strategy for HCC anti-recurrence, and its progression could be sensitively monitored by corresponding neoantigen mutations in ctDNA, and thus provided solid information for individualized medicine in HCC. Trial registration This study was registered at Chinese Clinical Trial Registry; Registration number: ChiCTR1900020990 .
Inequalities in Income and Education Are Associated With Survival Differences After Out-of-Hospital Cardiac Arrest: Nationwide Observational Study
Authors: Martin Jonsson, Juho Härkönen, Petter Ljungman, Per Nordberg, Mattias Ringh, Geir Hirlekar, Araz Rawshani, Johan Herlitz, Rickard Ljung, Jacob Hollenberg
Journal: Circulation (2021)

Despite the acknowledged importance of socioeconomic factors as regards cardiovascular disease onset and survival, the relationship between individual-level socioeconomic factors and survival after out-of-hospital cardiac arrest is not established. Our aim was to investigate whether socioeconomic variables are associated with 30-day survival after out-of-hospital cardiac arrest.We linked data from the Swedish Registry for Cardiopulmonary Resuscitation with individual-level data on socioeconomic factors (ie, educational level and disposable income) from Statistics Sweden. Confounding and mediating variables included demographic factors, comorbidity, and Utstein resuscitation variables. Outcome was 30-day survival. Multiple modified Poisson regression was used for the main analyses.A total of 31 373 out-of-hospital cardiac arrests occurring in 2010 to 2017 were included. Crude 30-day survival rates by income quintiles were as follows: Q1 (low), 414/6277 (6.6%); Q2, 339/6276 (5.4%); Q3, 423/6275 (6.7%); Q4, 652/6273 (10.4%); and Q5 (high), 928/6272 (14.8%). In adjusted analysis, the chance of survival by income level followed a gradient-like increase, with a risk ratio of 1.86 (95% CI, 1.65-2.09) in the highest-income quintile versus the lowest. This association remained after adjusting for comorbidity, resuscitation factors, and initial rhythm. A higher educational level was associated with improved 30-day survival, with the risk ratio associated with postsecondary education ≥4 years being 1.51 (95% CI, 1.30-1.74). Survival disparities by income and educational level were observed in both men and women.In this nationwide observational study using individual-level socioeconomic data, higher income and higher educational level were associated with better 30-day survival after out-of-hospital cardiac arrest in both sexes.
Sensitivity and specificity of surveillance case definitions in detection of influenza and respiratory syncytial virus among hospitalized patients, New Zealand, 2012–2016
Authors: William Davis, Jazmin Duque, Q. Sue Huang, Natalie Olson, Cameron C. Grant, E. Claire Newbern, Mark Thompson, Ben Waite, Namrata Prasad, Adrian Trenholme, Eduardo Azziz-Baumgartner
Journal: Journal of Infection (2021)
Diastolic Dysfunction in Systemic Sclerosis: Risk Factors and Impact on Mortality
Authors: Alicia M. Hinze, Jamie Perin, Adrianne Woods, Laura K. Hummers, Fredrick M. Wigley, Monica Mukherjee, Ami A. Shah
Journal: Arthritis & Rheumatology (2021)

Objective To determine the independent risk factors for diastolic dysfunction (DD) in patients with systemic sclerosis (SSc) and to evaluate the impact of DD on mortality. Methods SSc patients enrolled in the Johns Hopkins Scleroderma Center Cohort between November 1, 2006 and November 1, 2017 with ≥1 analyzable 2‐dimensional (2‐D) echocardiogram in our system were included (n = 806). DD risk factors and SSc disease characteristics were prospectively obtained, and the presence or absence of DD was determined using the most recent 2‐D echocardiogram. Logistic regression models examined associations between clinical risk factors and DD, and Cox proportional hazards models were used to assess survival. Results DD was present in 18.6% of participants. The majority of participants were female (84%) with a median age of 58.4 years (interquartile range 48.8–68.1). Older age (odds ratio [OR] 1.12 [95% confidence interval (95% CI) 1.09–1.15], P &lt; 0.001), coronary artery disease (OR 3.69 [95% CI 1.52–8.97], P = 0.004), obesity (OR 4.74 [95% CI 2.57–8.74], P &lt; 0.001), longer SSc disease duration (OR 1.04 [95% CI 1.01–1.06], P = 0.004), diffusing capacity for carbon monoxide ≤60% of predicted (OR 2.41 [95% CI 1.40–4.16], P = 0.002), and history of scleroderma renal crisis (OR 3.18 [95% CI 1.12–9.07], P = 0.031) were all independently associated with an increased risk of DD. Anti–Scl‐70 positivity (OR 0.49 [95% CI 0.26–0.93], P = 0.03) and severe gastrointestinal disease (OR 0.48 [95% CI 0.30–0.79], P = 0.004) were associated with a reduced risk of DD. The presence of DD was independently associated with an increase in the risk of mortality (hazard ratio 1.69 [95% CI 1.07–2.68], P = 0.027). Conclusion DD is independently associated with an increased risk of mortality in patients with SSc. Potentially modifiable risk factors, including coronary artery disease and obesity, should be addressed in patients with SSc to reduce mortality risk.
Histopathology-led quality evaluation of endoluminal excision specimens – not a bad idea!
Authors: Marnix Jansen
Journal: Endoscopy (2021)

Predicting tumor recurrence following endoluminal excision of early cancers of the upper gastrointestinal tract can be vexingly difficult. There are a handful of histopathologic criteria that can predict risk of local and distant tumor recurrence including invasion depth, tumor differentiation grade, and lymphovascular invasion [1]. Recent reporting standards from the International Collaboration on Cancer Reporting (ICCR) have now brought these parameters together in a proforma that can be used to harmonize histopathologic evaluation of endoluminal excision specimens and foster uniform interpretation between sites [2]. These reporting standards feature a panoply of essential criteria, such as those listed previously, as well as optional criteria, including histopathologic tumor type, for which the impact on patient management is currently unclear. However, these risk prediction criteria are crude and some patients are unnecessarily overtreated, whilst others are dangerously undertreated [3] [4]. How can we do better? Are there any relevant reporting parameters that we have so far missed, which may have been hiding in plain sight?
Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population
Authors: Isabel Graupera, Maja Thiele, Miquel Serra-Burriel, Llorenç Caballeria, Dominique Roulot, Grace Lai-Hung Wong, Núria Fabrellas, Indra Neil Guha, Anita Arslanow, Carmen Expósito, Rosario Hernández, Guruprasad Padur Aithal, Peter R. Galle, Guillem Pera, Vincent Wai-Sun Wong, Frank Lammert, Pere Ginès, Laurent Castera, Aleksander Krag
Journal: Clinical Gastroenterology and Hepatology (2021)

Fibrosis-4 (FIB-4) and the nonalcoholic fatty liver disease fibrosis score (NFS) are the 2 most popular noninvasive blood-based serum tests proposed for widespread fibrosis screening. We therefore aimed to describe the accuracy of FIB-4 and NFS to detect elevated liver stiffness as an indicator of hepatic fibrosis in low-prevalence populations.This study included a total of 5129 patients with concomitant measurement of FIB-4, NFS, and liver stiffness measurement (LSM) by Fibroscan (Echosens, France) from 5 independent population-based cohorts from Spain, Hong Kong, Denmark, England, and France; 3979 participants from the general population and 1150 from at-risk cohorts due to alcohol, diabetes, or obesity. We correlated LSM with FIB-4 and NFS, and calculated pre- and post-test predictive values of FIB-4 and NFS to detect elevated LSM at 8 kPa and 12 kPa cutoffs. The mean age was 53 ± 12 years, the mean body mass index was 27 ± 5 kg/m2, and 2439 (57%) were women. One in 10 patients (552; 11%) had liver stiffness ≥8 kPa, but 239 of those (43%) had a normal FIB-4, and 171 (31%) had normal NFS. The proportion of false-negatives was higher in at-risk patients than the general population. FIB-4 was false-negative in 11% of diabetic subjects, compared with 2.5% false-negatives with NFS. Waist circumference outperformed FIB-4 and NFS for detecting LSM ≥8 kPa in the general population. Almost one-third (28%-29%) of elevated FIB-4/NFS were false-positive in both the general population and at-risk cohorts.FIB-4 and NFS are suboptimal for screening purposes due to a high risk of overdiagnosis and a non-negligible percentage of false-negatives, especially in patients with risk factors for chronic liver disease. Waist circumference emerged as a potential first step to identify patients at risk for liver fibrosis in the general population.
Clinical Impact of Immune Cells and Their Spatial Interactions in Diffuse Large B-Cell Lymphoma Microenvironment
Authors: Matias Autio, Suvi-Katri Leivonen, Oscar Brück, Marja-Liisa Karjalainen-Lindsberg, Teijo Pellinen, Sirpa Leppä
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Tumor-infiltrating immune cells have prognostic significance and are attractive therapeutic targets. Yet, the clinical significance of their spatial organization and phenotype in diffuse large B-cell lymphoma (DLBCL) is unclear. Experimental Design: We characterized T cells, macrophages, and their spatial interactions by multiplex IHC (mIHC) in 178 patients with DLBCL and correlated the data with patient demographics and survival. We validated the findings on gene expression data from two external DLBCL cohorts comprising 633 patients. Results: Macrophage and T-cell contents divided the samples into T cell–inflamed (60%) and noninflamed (40%) subgroups. The T cell–inflamed lymphoma microenvironment (LME) was also rich in other immune cells, defining immune hot phenotype, which did not as such correlate with outcome. However, when we divided the patients according to T-cell and macrophage contents, LME characterized by high T-cell/low macrophage content or a corresponding gene signature was associated with superior survival [5-year overall survival (OS): 92.3% vs. 74.4%, P = 0.036; 5-year progression-free survival (PFS): 92.6% vs. 69.8%, P = 0.012]. High proportion of PD-L1- and TIM3-expressing CD163− macrophages in the T cell–inflamed LME defined a group of patients with poor outcome [OS: HR = 3.22, 95% confidence interval (CI), 1.63–6.37, Padj = 0.011; PFS: HR = 2.76, 95% CI, 1.44–5.28, Padj = 0.016]. Furthermore, PD-L1 and PD-1 were enriched on macrophages interacting with T cells. Conclusions: Our data demonstrate that the interplay between macrophages and T cells in the DLBCL LME is immune checkpoint dependent and clinically meaningful.
Abstract 11901: CPR Quality During the COVID-19 Pandemic - More Evidence of Collateral Damage During Out-of-Hospital Cardiac Arrest
Authors: Jocasta Ball, Ziad Nehme, Melanie Villani, Karen L Smith
Journal: Circulation (2021)

Introduction: Many regions around the world have reported declining survival rates from out-of-hospital cardiac arrest (OHCA) during the COVID-19 pandemic. This has been attributed to COVID-19 infection and overwhelmed healthcare services in some regions and imposed social restrictions in others. However, the effect of the pandemic period on CPR quality, which has the potential to impact outcomes, has not yet been described. Methods: A retrospective observational study was performed using data collected in an established OHCA registry in Victoria, Australia. During a pre-pandemic period (11 February 2019-31 January 2020) and the COVID-19 pandemic period (1 February 2020-31 January 2021), 1,111 and 1,349 cases with attempted resuscitation had complete CPR quality data, respectively. The proportion of cases where CPR targets (chest compression fraction [CCF]≥90%, compression depth 5-10cm, compression rate 100-120 per minute, pre-shock pauses &lt;6 seconds, post-shock pauses &lt;5 seconds) were met was compared between the pre-pandemic and pandemic periods. Logistic regression was performed to identify the independent effect of the COVID-19 pandemic on achieving CPR targets. Results: The proportion of arrests where CCF≥90% significantly decreased during the pandemic (57% vs 74% in the pre-pandemic period, p&lt;0.001) as did the proportion with pre-shock pauses &lt;6 seconds (54% vs 62%, p=0.019) and post-shock pauses &lt;5 seconds (68% vs 82%, p&lt;0.001). However, the proportion within target compression rate significantly increased during the pandemic (64% vs 56%, p&lt;0.001). Following multivariable adjustment, the COVID-19 pandemic period was independently associated with a decrease in the odds of achieving a CCF≥90% (adjusted odds ratio [AOR] 0.47 [95% CI 0.40, 0.56]), a decrease in the odds of achieving pre-shock pauses&lt;6 seconds (AOR 0.71 [95% CI 0.52, 0.96]), and a decrease in the odds of achieving post-shock pauses&lt;5 seconds (AOR 0.49 [95% CI 0.34, 0.71]). Conclusion: CPR quality was impacted during the COVID-19 pandemic period which may have contributed to a decrease in OHCA survival previously identified. These findings reinforce the importance of maintaining effective resuscitation practices despite changes to clinical context.
The kinase complex mTORC2 promotes the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis
Authors: Yifei Wang, Qin Tian, Yaxing Hao, Wei Yao, Jinjin Lu, Cheng Chen, Xiangyu Chen, Yao Lin, Qizhao Huang, Lifan Xu, Jianjun Hu, Shun Lei, Zhengping Wei, Yuan Luo, Zhirong Li, Li Hu, Jianfang Tang, Qing Wu, Xinyuan Zhou, Yuzhang Wu, Zhinan Yin, Jianqing Xu, Lilin Ye
Journal: Nature Immunology (2021)
Polyphosphate-crosslinked collagen scaffolds for hemostasis and alveolar bone regeneration after tooth extraction
Authors: Jun-ting Gu, Kai Jiao, Jing Li, Jian-fei Yan, Kai-yan Wang, Fu Wang, Yan Liu, Franklin R. Tay, Ji-hua Chen, Li-na Niu
Journal: Bioactive Materials (2021)

Post-extraction bleeding and alveolar bone resorption are the two frequently encountered complications after tooth extraction that result in poor healing and rehabilitation difficulties. The present study covalently bonded polyphosphate onto a collagen scaffold (P-CS) by crosslinking. The P-CS demonstrated improved hemostatic property in a healthy rat model and an anticoagulant-treated rat model. This improvement is attributed to the increase in hydrophilicity, increased thrombin generation, platelet activation and stimulation of the intrinsic coagulation pathway. In addition, the P-CS promoted the in-situ bone regeneration and alveolar ridge preservation in a rat alveolar bone defect model. The promotion is attributed to enhanced osteogenic differentiation of bone marrow stromal cells. Osteogenesis was improved by both polyphosphate and blood clots. Taken together, P-CS possesses favorable hemostasis and alveolar ridge preservation capability. It may be used as an effective treatment option for post-extraction bleeding and alveolar bone loss.Collagen scaffold is commonly used for the treatment of post-extraction bleeding and alveolar bone loss after tooth extraction. However, its application is hampered by insufficient hemostatic and osteoinductive property. Crosslinking polyphosphate with collagen produces a modified collagen scaffold that possesses improved hemostatic performance and augmented bone regeneration potential.
Phase 1b Trial of Talazoparib and Gemtuzumab Ozogamicin in Adult Patients with CD33+ Relapsed or Refractory Acute Myeloid Leukemia
Authors: Mahesh Swaminathan, Amanda Przespolewski, Elizabeth A. Griffiths, James E. Thompson, Amro Elshoury, Wendy Walinski, Meriem Said, Stephanie Halliwell, Claire Puff, Kristopher Attwood, Eunice S. Wang
Journal: Blood (2021)
Non-invasive longitudinal imaging of VEGF-induced microvascular alterations in skin wounds
Authors: Yu-Hang Liu, Lorenz M. Brunner, Johannes Rebling, Maya Ben-Yehuda Greenwald, Sabine Werner, Michael Detmar, Daniel Razansky
Journal: Theranostics (2021)

Background: Microcirculation is essential for skin homeostasis and repair. A variety of growth factors have been identified as important regulators of wound healing. However, direct observation and longitudinal monitoring of skin remodeling in an unperturbed in vivo environment remains challenging. Methods: We report on non-invasive longitudinal imaging of the wound healing process in transgenic mice overexpressing vascular endothelial growth factor A (VEGF-A) in keratinocytes by means of large-scale optoacoustic microscopy (LSOM). This rapid, label-free, high throughput intravital microscopy method averts the use of dorsal skin-fold chambers, allowing for fully non-invasive repeated imaging of intact wounds with capillary resolution over field-of-view spanning several centimeters. Results: We observed VEGF-driven enhancement of dermal vascularization in ears, dorsal skin and healing wounds and quantified the hemoglobin content, fill fraction, vessel diameter and tortuosity. The in vivo findings were further corroborated by detailed side-by-side classical histological whole-mount vascular stainings and pan-endothelial CD31 immunofluorescence. Conclusion: The new approach is suitable for supplementing or replacing the cumbersome histological procedures in a broad range of skin regeneration and tissue engineering applications.
The effect of mandatory COVID-19 certificates on vaccine uptake: synthetic-control modelling of six countries
Authors: Melinda C Mills, Tobias Rüttenauer
Journal: The Lancet Public Health (2021)

Mandatory COVID-19 certification (showing vaccination, recent negative test, or proof of recovery) has been introduced in some countries. We aimed to investigate the effect of certification on vaccine uptake.We designed a synthetic control model comparing six countries (Denmark, Israel, Italy, France, Germany, and Switzerland) that introduced certification (April-August, 2021), with 19 control countries. Using daily data on cases, deaths, vaccinations, and country-specific information, we produced a counterfactual trend estimating what might have happened in similar circumstances if certificates were not introduced. The main outcome was daily COVID-19 vaccine doses.COVID-19 certification led to increased vaccinations 20 days before implementation in anticipation, with a lasting effect up to 40 days after. Countries with pre-intervention uptake that was below average had a more pronounced increase in daily vaccinations compared with those where uptake was already average or higher. In France, doses exceeded 55 672 (95% CI 49 668-73 707) vaccines per million population or, in absolute terms, 3 761 440 (3 355 761-4 979 952) doses before mandatory certification and 72 151 (37 940-114 140) per million population after certification (4 874 857 [2 563 396-7 711 769] doses). We found no effect in countries that already had average uptake (Germany), or an unclear effect when certificates were introduced during a period of limited vaccine supply (Denmark). Increase in uptake was highest for people younger than 30 years after the introduction of certification. Access restrictions linked to certain settings (nightclubs and events with >1000 people) were associated with increased uptake in those younger than 20 years. When certification was extended to broader settings, uptake remained high in the youngest group, but increases were also observed in those aged 30-49 years.Mandatory COVID-19 certification could increase vaccine uptake, but interpretation and transferability of findings need to be considered in the context of pre-existing levels of vaccine uptake and hesitancy, eligibility changes, and the pandemic trajectory.Leverhulme Trust and European Research Council.
Prostaglandin Pathways: Opportunities for Cancer Prevention and Therapy
Authors: Qiushi Wang, Rebecca J. Morris, Ann M. Bode, Tianshun Zhang
Journal: Cancer Research (2021)

Abstract Because of profound effects observed in carcinogenesis, prostaglandins (PG), prostaglandin-endoperoxide synthases, and PG receptors are implicated in cancer development and progression. Understanding the molecular mechanisms of PG actions has potential clinical relevance for cancer prevention and therapy. This review focuses on the current status of PG signaling pathways in modulating cancer progression and aims to provide insights into the mechanistic actions of PGs and their receptors in influencing tumor progression. We also examine several small molecules identified as having anticancer activity that target prostaglandin receptors. The literature suggests that targeting PG pathways could provide opportunities for cancer prevention and therapy.
Primary Central Nervous System Involvement at Initial Diagnosis Remains an Independent Risk Factor for Relapse in Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Cell Transplantation in CR1
Authors: Mohamed A. Kharfan-Dabaja, Myriam Labopin, Ali Bazarbachi, Urpu Salmenniemi, Stephan Mielke, Patrice Chevallier, Marie Thérèse Rubio, Marie Balsat, Pietro Pioltelli, Anne-Lise Menard, Gerard Socie, Anne Huynh, Nicolaas Schaap, Arancha Bermudez Rodriguez, Jan J. Cornelissen, Ibrahim Yakoub-Agha, Mahmoud Aljurf, Sebastian Giebel, Eolia Brissot, Zinaida Peric, Arnon Nagler, Mohamad Mohty
Journal: Blood (2021)