bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of cancer therapies on physical fitness before oesophagogastric cancer surgery: a prospective, blinded, multi-centre, observational, cohort study
Authors: West Malcolm A. , Anastasiou Zachos , Ambler Gareth , Loughney Lisa , Mythen Michael G. , Owen Thomas , Danjoux Gerard , Levett Denny Z.H. , Calverley Peter M.A. , Kelly Jamie J. , Jack Sandy , Grocott Michael P.W. ,   Fit4Surgery Consortium
Published: June 2021

Background: Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. Methods: Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). Results: In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg-1.min-1 (-1.80 to -0.69) and -3.02ml.kg-1.min-1 (-3.85 to -2.20); p<0.0001). Baseline chemo/chemoradiotherapy anaerobic threshold and peak were associated with one-year mortality (HR=0.72, 95%CI 0.59 to 0.88; p=0.001 and HR=0.85, 0.76 to 0.95; p=0.005). The change in physical fitness was not associated with one-year mortality. Conclusion: Chemo/chemoradiotherapy prior to oesophagogastric cancer surgery reduced physical fitness. Lower baseline fitness was associated with reduced overall survival at one-year. Careful consideration of fitness prior to chemo/chemoradiotherapy and surgery is urgently needed.
The Groundless Use of Linearity in Daily Thinking and Decision-making
Authors: Duma László 
Published: June 2021

The overuse or groundless use of linearity, that is the fallacy of omnipotent linearity, intertwines our everyday lives and decisions. The misconception of linearity is not an isolated phenomenon, yet we do not handle this question in the proper way. The examples of MPG (Miles per Gallon) and MPH (Miles per Hour) or driving speed have something else in common: there is a widely used indicator conveying a false impression about the nature and physical, economical effects of the described phenomena by creating the illusion of linearity, leading to faulty decisions. In this paper, I show the common cases where we often make linear mistakes, and for which I can give illustrations drawn from scientific publications or everyday examples. Fresh survey research has been done in order to reveal the presence of linearity in the daily decision-making in terms of its groundless use. The article also identifies some common roots to the problem; it also outlines the psychological mechanisms and possible policies to help avoid them.
Retrospect: EC’s Merger Reformation of 2004
Authors: Salonen Antti 
Published: June 2021

This article examines in detail the European Commission’s main instrument in aiding the fluency of merger procedures, the Best Practices on the conduct of EC merger proceedings guideline, and portrays its positive effect on the regulatory transition phase of 2004, when the new EC Merger regulation 139/2004 came into force.
Relevant background information concerning the legal context is provided in order to illustrate the anticipated hazards of the transition phase, which in retrospect never actualised. This paper seeks to answer how this scenario was avoided: What measures did the Directorate General for Competition take and as a result, what effect did this have on business communities’ freedoms and responsibilities. These conclusions are drawn from 2004’s statistical survey on European merger control.
The Blackstone/Acetex case of 2004 is provided as a case study to demonstrate the potential complications of the official merger procedure and to emphasize the importance of a well-managed pre-notification procedure preceding the actual concentration. In addition, the Commission’s increased powers to issue fines are illustrated in the form its former decisions, where the concentrating parties neglected to comply with EC competition rules.
Portrait of Italian Cardio-Oncology: Results of a Nationwide Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Survey
Authors: Canale Maria Laura , Turazza Fabio , Lestuzzi Chiara , Parrini Iris , Camerini Andrea , Russo Giulia , Colivicchi Furio , Gabrielli Domenico , Gulizia Michele Massimo , Oliva Stefano , Tarantini Luigi , Maurea Nicola , Rigacci Luigi , Petrolati Sandro , Casolo Giancarlo , Bisceglia Irma 
Published: June 2021

Aims: Cardio-oncology has achieved a pivotal role in science, but real world data on its clinical impact are still limited.Methods: A questionnaire was sent out to all cardio-oncology services across Italy (n = 120). The questionnaire was made up of 28 questions divided into four blocks: (A) general information on hospitals and service, (B) the inner organization of cardio-oncology and its relationships with out-of-hospital cardiologists and general practitioners, (C) educational needs and referral guidelines, and (D) activities/specific workload.Results: Ninety-six out of 120 (80%) completed the questionnaire; 9.4% were cancer centers while 90.6% were general hospitals. A cardio-oncology team was present in 56% of the cancer centers and in 20% only of general hospitals, and a cardio-oncology pathway was active in 55% of cancer centers and in just 14% of the general hospitals. Relationships with out-of-hospital cardiologists and general practitioners were lacking. The guidelines of reference were ESC and ANMCO/AIOM. Patients receiving anthracycline chemotherapy underwent scheduled monitoring by means of echocardiography in 58% of cases. Routine use of cardiac damage biomarkers was overall low, ranging from 22 to 33% while the use of global longitudinal strain reached 44%.Conclusions: Italian cardio-oncology showed a growing influence on clinical practice but still has room for improvement. Cardio-oncology teams are still scarce, and the application of dedicated paths is poor. The need for specific training has been highlighted.
In Vivo Sustained Release of Peptide Vaccine Mediated by Dendritic Mesoporous Silica Nanocarriers
Authors: An Weiteng , Defaus Sira , Andreu David , Rivera-Gil Pilar 
Published: June 2021

Mesoporous silica nanoparticles have drawn increasing attention as promising candidates in vaccine delivery. Previous studies evaluating silica-based vaccine delivery systems concentrated largely on macromolecular antigens, such as inactivated whole viruses. In this study, we synthesized dendritic mesoporous silica nanoparticles (DMSNs), and we evaluated their effectiveness as delivery platforms for peptide-based subunit vaccines. We encapsulated and tested in vivo an earlier reported foot-and-mouth disease virus (FMDV) peptide vaccine (B2T). The B2T@DMSNs formulation contained the peptide vaccine and the DMSNs without further need of other compounds neither adjuvants nor emulsions. We measured in vitro a sustained release up to 930 h. B2T@DMSNs-57 and B2T@DMSNs-156 released 23.7% (135 µg) and 22.8% (132 µg) of the total B2T. The formation of a corona of serum proteins around the DMSNs increased the B2T release up to 61% (348 µg/mg) and 80% (464 µg/mg) for B2T@DMSNs-57 and B2T@DMSNs-156. In vitro results point out to a longer sustained release, assisted by the formation of a protein corona around DMSNs, compared to the reference formulation (i.e., B2T emulsified in Montanide). We further confirmed in vivo immunogenicity of B2T@DMSNs in a particle size-dependent manner. Since B2T@DMSNs elicited specific immune responses in mice with high IgG production like the reference B2T@Montanide™, self-adjuvant properties of the DMSNs could be ascribed. Our results display DMSNs as efficacious nanocarriers for peptide-based vaccine administration.
The Safety and Immunogenicity of the mRNA-BNT162b2 SARS-CoV-2 Vaccine in Hemodialysis Patients
Authors: Zitt Emanuel , Davidovic Tamara , Schimpf Judith , Abbassi-Nik Armin , Mutschlechner Beatrix , Ulmer Hanno , Benda Magdalena A. , Sprenger-Mähr Hannelore , Winder Thomas , Lhotta Karl 
Published: June 2021

BackgroundHemodialysis patients are at high risk for severe COVID-19. SARS-CoV-2 vaccination related safety and immunogenicity data in these patients are rare.MethodsIn this observational study SARS-CoV-2-seronegative hemodialysis patients were vaccinated with two doses of the Pfizer/BioNTech mRNA-BNT162b2 vaccine (COMIRNATY® 30 µg) and followed for 90 days. Local and systemic side effects were assessed at every dialysis session during the first post-vaccination week after the first and second vaccine dose. Immunogenicity was determined four weeks after vaccination by quantifying anti-SARS-CoV-2 spike protein IgG antibodies (LIAISON® SARS-CoV-2-TrimericS IgG chemiluminescent immunoassay) expressed in binding activity units per milliliter (BAU/mL) adapted to the WHO International standard.ResultsFifty patients (32% women, 68% men) with a mean (SD) age of 67.6 (14.8) years were included. Mild local reactions occurred in 38% after the first injection, and in 29.2% with mild, in 2.1% with moderate and in 2.1% with severe degree after the second injection. Systemic reactive events occurred less often, with diarrhea (4% mild, 4% moderate) and fatigue (8% mild) being the most frequent ones. After the first injection 42% of the patients developed a positive response using the assay specific cut-off value of 33.8 binding activity units per milliliter (BAU/mL) with a median (Q1, Q3) anti-SARS-CoV-2 spike IgG concentration of 20.0 (11.7, 51.0) BAU/mL. After the second injection the percentage of seropositive patients increased to 97.9% with an anti-SARS-CoV-2 spike IgG concentration of 1075 (290.8, 1735) BAU/mL. Higher age and immunosuppression were associated with lower, calcitriol treatment and prior seroconversion to hepatitis B vaccination with significantly higher antibody concentration.ConclusionsThe mRNA-BNT162b2 SARS-CoV-2 vaccine appears to be safe and well-tolerated and shows a high immunogenicity in hemodialysis patients.
Derivation and Validation of a Nomogram for Predicting 90-Day Survival in Patients With HBV-Related Acute-on-Chronic Liver Failure
Authors: Chen Jun-feng , Weng Wei-zhen , Huang Miao , Peng Xiao-hua , He Jian-rong , Zhang Jing , Xiong Jing , Zhang Shao-quan , Cao Hui-juan , Gao Bin , Lin Deng-na , Gao Juan , Gao Zhi-liang , Lin Bing-liang 
Published: June 2021

Background: Conventional prognostic models do not fully reflect the severity of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to establish an effective and convenient nomogram for patients with HBV-related ACLF.Methods: A nomogram was developed based on a retrospective cohort of 1,353 patients treated at the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to June 2016. The predictive accuracy and discriminatory ability of the nomogram were determined by a concordance index (C-index) and calibration curve, and were compared with current scoring systems. The results were validated using an independent retrospective cohort of 669 patients consecutively treated at the same institution from July 2016 to March 2018. This study is registered at ClinicalTrials.gov (NCT03992898).Results: Multivariable analysis of the derivation cohort found that independent predictors of 90-day survival were age, white blood cell (WBC) count, hemoglobin (Hb), aspartate aminotransferase (AST), total bilirubin (TBil), international normalized ratio, serum creatinine (Cr), alpha fetoprotein (AFP), serum sodium (Na), hepatic encephalopathy (HE), pre-existing chronic liver disease(PreLD), and HBV DNA load. All factors were included in the nomogram. The nomogram calibration curve for the probability of 90-day survival indicated that nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram was 0.790, which was statistically significantly greater than those for the current scoring systems in the derivation cohort (P &lt; 0.001). The results were confirmed in the validation cohort.Conclusions: The proposed nomogram is more accurate in predicting the 90-day survival of patients with HBV-related ACLF than current commonly used methods.
Ketogenic Diet Therapy for the Treatment of Post-encephalitic and Autoimmune-Associated Epilepsies
Authors: Husari Khalil S. , Cervenka Mackenzie C. 
Published: June 2021

Introduction: Acute Encephalitis is associated with a high risk of acute symptomatic seizures, status epilepticus, and remote symptomatic epilepsy. Ketogenic diet therapies (KDT) have been established as a feasible and safe adjunctive management of refractory- and super-refractory status epilepticus. However, the role of KDT in the chronic management of Post-encephalitic epilepsy (PE) and autoimmune-associated epilepsy (AE) is unknown. This study aims to investigate the use of KDT in patients with PE and AE.Methods: A retrospective single-center case series examining adult patients with PE and AE treated with the modified Atkins diet (MAD), a KDT commonly used by adults with drug-resistant epilepsy.Results: Ten patients with PE and AE who were treated with adjunctive MAD were included. Four patients had either confirmed or presumed viral encephalitis, five patients had seronegative AE, and one patient had GAD65 AE. The median latency between starting MAD and onset of encephalitis was 6 years (IQR: 1–10). The median duration of MAD was 10 months (IQR: 3.75–36). Three patients (30%) became seizure-free, one patient (10%) achieved 90% seizure freedom, and three patients (30%) achieved a 50–75% reduction in their baseline seizure frequency, while three patients (30%) had no significant benefit. Overall, seven patients (70%) achieved ≥50% seizure reduction.Conclusion: In addition to its established role in the treatment of RSE, KDT may be a safe and feasible option for the treatment of chronic PE and AE, particularly in those with prior history of SE. Prospective studies are warranted to explore the efficacy of KDT in management of patients with PE and AE.
Early Effects of Passive Leg-Raising Test, Fluid Challenge, and Norepinephrine on Cerebral Autoregulation and Oxygenation in COVID-19 Critically Ill Patients
Authors: Robba Chiara , Messina Antonio , Battaglini Denise , Ball Lorenzo , Brunetti Iole , Bassetti Matteo , Giacobbe Daniele R. , Vena Antonio , Patroniti Nicolo' , Cecconi Maurizio , Matta Basil F. , Liu Xiuyun , Rocco Patricia R. M. , Czosnyka Marek , Pelosi Paolo 
Published: June 2021

Background: Coronavirus disease 2019 (COVID-19) patients are at high risk of neurological complications consequent to several factors including persistent hypotension. There is a paucity of data on the effects of therapeutic interventions designed to optimize systemic hemodynamics on cerebral autoregulation (CA) in this group of patients.Methods: Single-center, observational prospective study conducted at San Martino Policlinico Hospital, Genoa, Italy, from October 1 to December 15, 2020. Mechanically ventilated COVID-19 patients, who had at least one episode of hypotension and received a passive leg raising (PLR) test, were included. They were then treated with fluid challenge (FC) and/or norepinephrine (NE), according to patients' clinical conditions, at different moments. The primary outcome was to assess the early effects of PLR test and of FC and NE [when clinically indicated to maintain adequate mean arterial pressure (MAP)] on CA (CA index) measured by transcranial Doppler (TCD). Secondary outcomes were to evaluate the effects of PLR test, FC, and NE on systemic hemodynamic variables, cerebral oxygenation (rSo2), and non-invasive intracranial pressure (nICP).Results: Twenty-three patients were included and underwent PLR test. Of these, 22 patients received FC and 14 were treated with NE. The median age was 62 years (interquartile range = 57–68.5 years), and 78% were male. PLR test led to a low CA index [58% (44–76.3%)]. FC and NE administration resulted in a CA index of 90.8% (74.2–100%) and 100% (100–100%), respectively. After PLR test, nICP based on pulsatility index and nICP based on flow velocity diastolic formula was increased [18.6 (17.7–19.6) vs. 19.3 (18.2–19.8) mm Hg, p = 0.009, and 12.9 (8.5–18) vs. 15 (10.5–19.7) mm Hg, p = 0.001, respectively]. PLR test, FC, and NE resulted in a significant increase in MAP and rSo2.Conclusions: In mechanically ventilated severe COVID-19 patients, PLR test adversely affects CA. An individualized strategy aimed at assessing both the hemodynamic and cerebral needs is warranted in patients at high risk of neurological complications.
Tumor Immune Microenvironment Components and Checkpoint Molecules in Anaplastic Variant of Diffuse Large B-Cell Lymphoma
Authors: Xu Tianqi , Chai Jia , Wang Kaijing , Jia Qingge , Liu Yixiong , Wang Yingmei , Xu Junpeng , Yu Kangjie , Zhao Danhui , Ma Jing , Fan Linni , Yan Qingguo , Guo Shuangping , Chen Gang , Chen Qiongrong , Xiao Hualiang , Liu Fang , Qi Chubo , Liang Rong , Li Mingyang , Wang Zhe 
Published: June 2021

BackgroundAnaplastic diffuse large B-cell lymphoma(A-DLBCL) is a rare morphological subtype characterized by the presence of polygonal, bizarre-shaped tumor cells. Our previous research found that A-DLBCL displays many genetic alterations and biological features that differ greatly from those of ordinary DLBCL. However, the status of tumor immune microenvironment components and checkpoint molecules in A-DLBCL remains unclear.MethodsThirty A-DLBCL patients were enrolled to study tumor immune microenvironment components and checkpoint molecules and their associations with clinicopathological features and prognosis.ResultsPatients with A-DLBCL presented higher expression of PD-L1 (40%vs10%, P=0.004) than patients with ordinary DLBCL. FISH analysis showed that extra copies of PD-L1 were more frequent in A-DLBCL cases than in ordinary DLBCL cases (23.3%vs4.0%, P=0.001). The numbers of PD-1+TILs (tumor infiltrating lymphocytes) and CD8+T cells were significantly lower in A-DLBCL versus ordinary DLBCL. In contrast, the numbers of GATA3+Th2 cells, FOXP3+Tregs and CD33+myeloid-derived suppressor cells (MDSCs) were significantly higher in A-DLBCL than in ordinary DLBCL. The associations between clinicopathological features and tumor immune microenvironment cell frequency were analyzed in A-DLBCL patients. Briefly, the number of PD-1+TILs was lower and the number of CD33+MDSCs was higher in patients with mutatedTP53compared to those with wild-typeTP53. The number of FOXP3+Tregs was much lower in patients with a noncomplete response (CR) to chemotherapy than in those with a complete response. The number of CD8+T cells showed a decreasing trend in patients with high International Prognostic Index (IPI) scores and in those with concurrent MYC and BCL2 and/or BCL6 abnormalities. Univariate survival analysis showed that patients with PD-L1+, mPD-L1+(PD-L1+nonmalignant stromal cells) or mPD-L1+status had a significantly poorer overall survival (OS) than those with PD-L1-status. An increase in the number of CD3+T cells, FOXP3+Treg cells and T-bet+Th1 cells was significantly associated with prolonged OS in patients with A-DLBCL.ConclusionOur study suggests that A-DLBCL displays a distinct pattern of tumor immune microenvironment components and checkpoint molecules that distinguish it from ordinary DLBCL. The analysis of tumor immune microenvironment components and checkpoint molecules could help in predicting the prognosis of A-DLBCL patients and determining therapeutic strategies targeting the tumor immune microenvironment.
Current Triple-Negative Breast Cancer Subtypes: Dissecting the Most Aggressive Form of Breast Cancer
Authors: Ensenyat-Mendez Miquel , Llinàs-Arias Pere , Orozco Javier I. J. , Íñiguez-Muñoz Sandra , Salomon Matthew P. , Sesé Borja , DiNome Maggie L. , Marzese Diego M. 
Published: June 2021

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease defined by the absence of estrogen receptor (ER) and progesterone receptor (PR) expression, and human epidermal growth factor receptor 2 (HER2) overexpression that lacks targeted treatments, leading to dismal clinical outcomes. Thus, better stratification systems that reflect intrinsic and clinically useful differences between TNBC tumors will sharpen the treatment approaches and improve clinical outcomes. The lack of a rational classification system for TNBC also impacts current and emerging therapeutic alternatives. In the past years, several new methodologies to stratify TNBC have arisen thanks to the implementation of microarray technology, high-throughput sequencing, and bioinformatic methods, exponentially increasing the amount of genomic, epigenomic, transcriptomic, and proteomic information available. Thus, new TNBC subtypes are being characterized with the promise to advance the treatment of this challenging disease. However, the diverse nature of the molecular data, the poor integration between the various methods, and the lack of cost-effective methods for systematic classification have hampered the widespread implementation of these promising developments. However, the advent of artificial intelligence applied to translational oncology promises to bring light into definitive TNBC subtypes. This review provides a comprehensive summary of the available classification strategies. It includes evaluating the overlap between the molecular, immunohistochemical, and clinical characteristics between these approaches and a perspective about the increasing applications of artificial intelligence to identify definitive and clinically relevant TNBC subtypes.