bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of pre-treatment may not increase the immune-related adverse events of RCC patients treated with nivolumab
Authors: Mizutani Kosuke , Ito Toshiki , Takahara Kiyoshi , Ando Ryosuke , Ishihara Takuma , Yasui Takahiro , Shiroki Ryoichi , Miyake Hideaki , Koie Takuya 
Published: March 2021

Abstract
Nivolumab has shown good prognosis in renal cell carcinoma (RCC) patients previously treated with targeted therapy. We aimed to study irAE (immune-related adverse event) due to nivolumab and numbers of previous treatment lines in RCC patients. Between October 2016 and November 2019, 114 patients were treated with nivolumab as second- and later-line therapy. Among them, 110 patients with complete data were evaluated in this retrospective observational study. The primary endpoint was the relation between irAE and numbers of previous targeted therapies. Secondary endpoints were the relation of irAE with the duration of nivolumab treatment and with best overall response. For the primary analysis, proportional odds logistic regression was used to assess the effect of the number of prior therapies on the grade of any irAE as the ordinal variable. For the secondary analysis, binomial logistic regression models adjusted for the covariates were prepared to confirm the association between the incidence of irAE and the number of courses, number of nivolumab treatments and best overall response. Overall, 69, 66, 33, 13, 9 and 9 patients were treated with sunitinib, axitinib, pazopanib, sorafenib, temsirolimus and everolimus, respectively, prior to nivolumab. In total, 60 adverse events (Grade 1, 21; Grade 2, 21; Grade 3, 14; Grade 4, 2; not evaluated, 2) were identified in the patients treated with nivolumab. Ordered logistic regression analysis showed that the adjusted odds ratios of numbers of prior treatment for grade of irAE were 1.12 (numbers of prior treatment: 2 to 1) and 1.31 (3 to 1). Odds ratios of the numbers of nivolumab treatments and best overall response for the incidence of irAE were not significant. No statistically significant relations were found between grade of irAE and numbers of treatments prior to nivolumab. Patients treated with nivolumab should be closely monitored for irAE regardless number of previous therapies.
Autoimmune manifestations associated with myelodysplastic syndrome predict a poor prognosis
Authors: Arinobu Yojiro , Kashiwado Yusuke , Miyawaki Kohta , Ayano Masahiro , Kimoto Yasutaka , Mitoma Hiroki , Akahoshi Mitsuteru , Miyamoto Toshihiro , Horiuchi Takahiko , Akashi Koichi , Niiro Hiroaki 
Published: March 2021

Abstract
We evaluated the clinical characteristics of autoimmune manifestations (AIMs) associated with myelodysplastic syndrome (MDS) to elucidate whether AIMs impacted MDS outcomes in Japan.
This retrospective study including 61 patients who received a new diagnosis of MDS between January 2008 and December 2015 was conducted by the review of electronic medical records for the presence of AIMs within a 1-year period prior to or following the diagnosis of MDS.
AIMs were identified in 12 of the 61 (20.0%) patients with MDS. The neutrophil counts and C-reactive protein levels in peripheral blood were significantly elevated in patients with AIMs, and the survival was shorter in those with AIMs compared to those without AIMs. Multivariate analysis demonstrated that the presence of AIMs and higher-risk disease according to the International Prognositic Scoring System (IPSS) were independent risk factors for increased mortality (hazard ratio, 4.76 and 4.79, respectively).
This retrospective study revealed that the prognosis was poor in patients with MDS-associated AIMs. The treatment of MDS using the current algorithms is based on prognostic scoring systems such as IPSS. Treatment strategies for patients with MDS-associated AIMs should be reconsidered, even in those with low-risk MDS according to the IPSS.
Cell cycle regulation in human hair follicle dermal papilla cells using nonthermal atmospheric pressure plasma-activated medium
Authors: Lee Jin-Woo , Kim Kyungsook , Jung Minhyung , Kim Youngsun 
Published: March 2021

Abstract
Nonthermal atmospheric pressure (NAP) plasmas have recently been developed and have been used for wound healing, blood coagulation, and cancer therapy. NAP plasmas can induce either cell proliferation or cell death, depending on the dose. Due to their efficacy and application easily, plasma activated mediums (PAMs) have been used in human cells recently.
In atmosphere, NAP plasmas react with molecular content of air such as N2, O2, H2O vapor, etc, and generate a variety of reactive oxygen and nitrogen species. High reactive oxygen species (ROS) levels promote damage of cellular DNA, proteins, and lipids. Such damage can lead to cell-cycle arrest, and cellular death. However, low levels of ROS have been caused an increase in cell cycle progression.
Human skin is arranged in 3 layers, including (from top to bottom) the epidermis (and its appendages), the dermis, and the hypodermis. Human dermal papilla cells (DPCs) are located in the middle or even deep part of the dermis. DPCs play a key role in hair regeneration, and a lot of effort have been made to promote DPC hair formation ability. DPC is increased proliferation, delayed senescence, and enhanced hair by depending on the amount of ROS through the NAP-PAM treatment.
In this study, we used NAP plasmas to the human hair follicle DPCs exposed from 0 to 20 minutes, so we were investigated the effects of PAM on cell proliferation and cell cycle progression. After NAP-PAM treatment for 24 hours, cell cycle was arrested in the G0/G1 phase. The NAP-PAM-treated human hair follicle DPCs recovered gradually after 48 hours of the treatment compared to the untreated cells.
Therefore, this approach offers promising results for further application of NAP-PAM in clinical dermatology. In future, it can be applied clinically in the form of active water that can delay the progression of baldness and alopecia areata.
Fecal neopterin level determination: can be a useful screening test for colorectal polyps?
Authors: Kilciler Ayse Guldem , Kutluana Ufuk , Mizrak Soycan 
Published: March 2021

Background
Colorectal cancer (CRC) is a leading cause of cancer death worldwide. The main precursor lesion leading to CRC is the adenomatous colorectal polyp (CP). Nowadays, there is no recognized perfect screening test of CP and CRC. Neopterin is an important marker of cellular inflammation. In this study, we aimed to evaluate comparatively immunochromatographic fecal occult blood test (iFOBT) and fecal neopterin levels (FNLs) in patients with CP and controls.

Methods
One hundred eleven patients diagnosed with CP and 68 individuals with negative colonoscopy were included in the study. iFOBT and FNLs were assessed in patients and controls.

Results
FNLs and iFOBT positivity were significantly higher in patients with CP than in controls (17.15 ± 3.55 µmol/L/g vs. 12.25 ± 2.19 µmol/L/g, P = 0.00 and 46.8% vs. 14.8%, P = 0.00, respectively). FNLs were significantly higher in cases with adenomatous polyps than in hyperplastic polyps (P = 0.002). FNL ≥14.00 µmol/L/g was the best cutoff value to differentiate between patients with CP from controls (P = 0.000). A multiple logistic regression analysis showed that high FNL was positively correlated with presence, number, diameter of CPs, and presence of adenoma (P < 0.005). The sensitivity of high FNL for CP was 81.1%, which was superior to iFOBT positivity (47.7%, P < 0.001).

Discussion
FNL level is significantly increased in CPs. The FNL exhibited increased sensitivity for identifying CP and adenomatous lesions compared with iFOBT. FNL determination could have as a new screening and diagnostic test for CP.
Gastrointestinal manifestations of COVID-19: results from a European centre
Authors: Leal Tiago , Costa Emanuel , Arroja Bruno , Gonçalves Raquel , Alves Joana 
Published: March 2021

Background
Infection due to severe acute respiratory syndrome coronavirus 2 is typically associated with a respiratory syndrome, but gastrointestinal symptoms have been described in early reports from China. However, data from European centres are scarce.

Objectives
We aimed to characterise the gastrointestinal manifestations of patients with coronavirus disease 2019 (COVID-19) and their disease course.

Methods
Patients admitted at our centre between March and April 2020 with diagnosis of COVID-19 were included. Asymptomatic patients or those without symptom information were excluded. Clinical features, laboratory data and disease severity (mechanical ventilation, intensive care admission or death) were analysed.

Results
Two-hundred one patients were included (median age 71 years; 56.2% male). Digestive symptoms were reported by 60 (29.9%) patients during the disease course, being part of the disease presentation in 34 (16.9%). The most frequent were diarrhoea in 36 patients (17.9%). Patients with gastrointestinal symptoms were younger (P = 0.032), had higher haemoglobin levels (P = 0.002) and lower C-reactive protein (P = 0.045) and potassium levels (P = 0.004). Patients with digestive symptoms had less severe disease (28.3 vs. 44.0%; P = 0.038). Regarding liver damage, aspartate aminotransferase (AST) was elevated in 65.2% of patients and alanine aminotransferase (ALT) in 62.7%, but these patients did not present a more severe disease (elevated AST P = 0.062; elevated ALT P = 0.276).

Conclusion
A significant portion of COVID-19 patients have digestive symptoms, mostly at presentation. This should be taken into account in order to keep a high level of suspicion to reach an early diagnosis and setup infection control measures to control the transmission rate. This subgroup of patients appears to have a less severe disease course.
Clinical course and outcome among patients with acute pancreatitis and COVID-19
Authors: Kumar Vivek , Barkoudah Ebrahim , Souza Daniel A.T. , Jin David X. , McNabb-Baltar Julia 
Published: March 2021

Background
The data on clinical course and outcome of acute pancreatitis among patients with coronavirus disease 2019 (COVID-19) are sparse. In this study, we analyzed the clinical profiles of patients with COVID 19 and acute pancreatitis.

Methods
This retrospective study was conducted on Research Patient Data Registry data which was pooled from five Mass General Brigham Healthcare Network hospitals. We extracted data on demographics, symptoms, ICU transfer, mechanical ventilation, laboratories’ profiles, imaging findings, and patient outcomes.

Result
Of 985 screened adult patients, 17 were eligible for the study, 9 (52.9%) were admitted primarily for respiratory failure and developed acute pancreatitis after a median of 22.5 days (13–76 days) from the onset of COVID-19 symptoms. On contrary, eight patients presented with typical symptoms and were diagnosed with acute pancreatitis, the majority with mild severity (62.5%) on admission. Patients who were admitted primarily with severe COVID-19 illness were younger (median age 57 vs. 63 years), females (55.6 vs. 25%), of Hispanic ethnicity (55.6 vs. 25%), and obese (88.9 vs. 37.5%). The median peak lipase, C reactive protein, ferritin, lactate dehydrogenase, D-dimer were higher among patients who developed acute pancreatitis later during hospitalization. Patients who developed acute pancreatitis later also experienced higher episodes of necrotizing pancreatitis (11.1% vs. 0), thromboembolic complications (55.6 vs. 12.5%), and higher mortality (37.5 vs. 12.5%).

Conclusion
Acute pancreatitis is not common among patients with COVID-19. Patients with COVID-19 who had acute pancreatitis on admission had more benign course and overall better outcome as compared to the patients who developed acute pancreatitis during hospitalization.
The Association Between Risk Behaviors and Vaping Among Youth in New Mexico
Authors: Fatemi Nasrin N. , Cruz Theresa H. , Kesler Denece O. , Schiff Melissa A. 
Published: March 2021

Context:
Electronic-cigarette use, or vaping, among youth has increased substantially in recent years. Tobacco smoking shows a strong association with other risk behaviors, but the association between vaping and other risk behaviors has rarely been explored. We examine the relationship between youth vaping and substance use, risky driving behaviors, and lack of bicycle helmet use.

Program:
Data from the 2015 and 2017 New Mexico Youth Risk and Resiliency Survey were analyzed to evaluate the association between the use of e-cigarettes and other youth risk behaviors. Study participants were high school students, grades 9 to 12. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Evaluation:
A majority of students reported ever using e-cigarettes (54%). In 2015, e-cigarette users were more likely than nonusers to be Hispanic (65% vs 54%, P ≤ .001) and 16 years of age or older (58% vs 42%, P = .018). We found strong, statistically significant associations between e-cigarette use and not wearing a bicycle helmet (OR = 2.62, 95% CI: 1.95-3.51), texting while driving (OR = 2.18, 95% CI: 1.79-2.66), driving after drinking (OR = 2.95, 95% CI: 1.61-5.40), current marijuana use (OR = 6.38, 95% CI: 4.65-8.76), current painkiller use (OR = 2.47, 95% CI: 1.63-3.77), and current heroin use (OR = 0.15, 95% CI: 0.06-0.33). Driving after drinking was not significantly associated with e-cigarette use in 2017.

Discussion:
E-cigarette use is associated with multiple other risk behaviors among youth. Further research should focus on environmental and policy efforts to reduce access to e-cigarettes by youth as well as interventions that address the underlying causes of the constellation of risk behaviors.
Evaluation of Communication and Safety Behaviors During Hospital-Wide Code Response Simulation
Authors: Ren Dennis M. , Abrams Anna , Banigan Maureen , Batabyal Rachael , Chamberlain James M. , Garrow Amanda , Izem Rima , Nicholson Laura , Ottolini Mary , Patterson Mary , Sarnacki Rachel , Walsh Heather A. , Zaveri Pavan 
Published: March 2021

Introduction
To understand the baseline quality of team communication behaviors at our organization, we implemented institution-wide simulation training and measured the performance of safety behaviors of ad hoc teams in emergent situations.

Methods
Clinicians participated in 2 interprofessional video-recorded simulation scenarios, each followed by debriefing. Using a standardized evaluation instrument, 2 reviewers independently evaluated the presence or absence of desired team safety behaviors, including escalating care, sharing a mental model, establishing leadership, thinking out loud, and identifying roles and responsibilities. We also scored the quality of sharing the mental model, closed-loop communication, and overall team performance on a 7-point scale. Discordant reviews were resolved with scoring by an additional reviewer.

Results
A total of 1404 clinicians participated in 398 simulation scenarios, resulting in 257 usable videos. Overall, teams exhibited desired behaviors at the following frequencies: escalating care, 85%; sharing mental models, 66%; verbally establishing leadership, 6%; thinking out loud, 87%; and identifying roles and responsibilities, 27%. Across all reviews, the quality of the graded behaviors (of 7 points) was 2.8 for shared mental models, 3.3 for closed-loop communication, and 3.2 for overall team performance.

Conclusions
In a simulation setting with ad hoc teams, there was variable performance on completing safety behaviors and only a fair quality of graded communication behaviors. These results establish a baseline assessment of communication and teamwork behaviors and will guide future quality improvement interventions.
Genetic associations with severe COVID-19
Authors: Murphy Nicholas M. , Dite Gillian S. , Allman Richard 
Published: March 2021

AbstractIdentification of host genetic factors that predispose individuals to severe COVID-19 is important, not only for understanding the disease and guiding the development of treatments, but also for risk prediction when combined to form a polygenic risk score (PRS). Using population controls, Pairo-Castineira et al. identified 12 SNPs (a panel of 8 SNPs and a panel of 6 SNPs, with two SNPs in both panels) associated with severe COVID-19. Using controls with asymptomatic or mild COVID-19, we were able to replicate the association with severe COVID-19 for only three of their SNPs and found marginal evidence for an association for one other. When combined as an 8-SNP PRS and a 6-SNP PRS, we found no evidence of association with severe COVID-19. The difference in our results and the results of Pairo-Castineira et al. might be the choice of controls: population controls vs controls with asymptomatic or mild COVID-19.
Prevalence of anti-SARS-CoV-2 antibodies in Poznań, Poland, after the first wave of the COVID-19 pandemic
Authors: Lorent Dagny , Nowak Rafal , Roxo Carolina , Lenartowicz Elzbieta , Makarewicz Aleksandra , Zaremba Bartosz , Nowak Szymon , Kuszel Lukasz , Stefaniak Jerzy , Kierzek Ryszard , Zmora Pawel 
Published: March 2021

AbstractIn comparison to other European countries, during the first months of COVID-19 pandemic, Poland reported relatively low number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. To estimate the scale of pandemic in Poland, a serosurvey of antibodies against SARS-CoV-2 was performed after the first wave of COVID-19 in Europe (March – May 2020). Within this study, we collected samples from July 28 to September 24, 2020 and based on the ELISA results, we found that 1.67% (25/1500, 95%CI 1.13 - 2.45) of the Poznan (Poland) metropolitan area’s population had antibodies against SARS-CoV-2 after the first wave of COVID-19. However, the presence of anti-SARS-CoV-2 IgG antibodies was confirmed with immunoblot in 56% (14/25) samples, what finally resulted in decrease of seroprevalence, i.e. 0.93% (14/1500, 95%CI 0.56 - 1.56). The positive anti-SARS-CoV-2 IgG results were associated with age, occupation related to constant contact with people, travelling abroad, non-compliance with epidemiological recommendations and direct contact with the novel coronavirus. Our findings confirm the low SARS-CoV-2 incidence in Poland and imply that the population had little herd immunity heading into the second and third wave of the pandemic, and therefore herd immunity contributed little to prevent the high numbers of SARS-CoV-2 infections and COVID-19 related deaths in Poland during these subsequent waves.
Improved performance of saliva for the detection of the B.1.351 variant in South Africa
Authors: Chu Chun Yat , Marais Gert , Opperman Christoffel , Doolabh Deelan , Iranzadeh Arash , Marais Carisa , Cox Helen , Williamson Carolyn , Hardie Diana , Brink Adrian 
Published: March 2021

AbstractAssessment of the unknown performance of saliva for the detection of the novel SARS-CoV-2 variant of concern (VOC) B.1.351 (501Y.V2) lineage is essential as saliva has been shown to be an equivalent, less invasive and a less costly alternative to nasopharyngeal swabs for the molecular detection of SARS-CoV-2 infection in pre-variant studies. Between 1st August 2020 and 16th January 2021, we enrolled 410 eligible ambulatory participants who presented to Groote Schuur Hospital (GSH) in Cape Town, South Africa for SARS-CoV-2 testing. Of these, 300 were enrolled prior to, and 110 after, the initial detection and replacement of wild-type by the B.1.351 variant. All participants provided a supervised self-collected mid-turbinate (MT) and saliva (SA) swab, in addition to the standard HCW collected NP swab which were all tested by RT-PCR in an accredited diagnostic laboratory. Positive percent agreement to NP swab for SA swabs pre- and post-variant were 51.5% and 72.5% respectively while these values for MT swabs were 75.8% and 77.5%. The negative percent agreement for all swab types during all periods was >98%. The basis for this marked improvement of SA swabs as a diagnostic sample for B.1.351 virus is still being investigated.
Clustering of patient comorbidities within electronic medical records enables high-precision COVID-19 mortality prediction
Authors: Lannou Erwann Le , Post Benjamin , Haar Shlomi , Brett Stephen J. , Kadirvelu Balasundaram , Faisal A. Aldo 
Published: March 2021

AbstractWe present an explainable AI framework to predict mortality after a positive COVID-19 diagnosis based solely on data routinely collected in electronic healthcare records (EHRs) obtained prior to diagnosis. We grounded our analysis on the ½ Million people UK Biobank and linked NHS COVID-19 records. We developed a method to capture the complexities and large variety of clinical codes present in EHRs, and we show that these have a larger impact on risk than all other patient data but age. We use a form of clustering for natural language processing of the clinical codes, specifically, topic modelling by Latent Dirichlet Allocation (LDA), to generate a succinct digital fingerprint of a patient’s full secondary care clinical history, i.e. their comorbidities and past interventions. These digital comorbidity fingerprints offer immediately interpretable clinical descriptions that are meaningful, e.g. grouping cardiovascular disorders with common risk factors but also novel groupings that are not obvious. The comorbidity fingerprints differ in both their breadth and depth from existing observational disease associations in the COVID-19 literature. Taking this data-driven approach allows us to avoid human-induction bias and confirmation bias during selection of what are important potential predictors of COVID-19 mortality. Together with age, these digital fingerprints are the single most important factor in our predictor. This holds the potential for improving individual risk profiling for clinical decisions and the identification of groups for public health interventions such as vaccine programmes. Combining our digital precondition fingerprints with demographic characteristics allow us to match or exceed the performance of existing state-of-the-art COVID-19 mortality predictors (EHCF) which have been developed through expert consensus. Our precondition fingerprinting and entire mortality prediction analytics pipeline are designed so as to be rapidly redeployable, e.g. for COVID-19 variants or other pre-existing diseases.
Assessing the impact of multiple comorbidities on fatal outcome in young COVID-19
Authors: Monroy-Castillero Paulino , Friedman Eitan , Revuelta-Herrera Arturo , Yochelis Arik 
Published: March 2021

AbstractA Bayesian analysis with the use of a rank-biserial correlation algorithm was applied to identify the impact of multiple comorbid conditions on fatal COVID-19 outcome in young adult cases (40-50 years). The demonstration was conducted for a publicly available database provided by the Mexican authority, in the absence of other alternative free-access repositories with information per patient. The methodology here proposed showed that even in the face of small sample sizes, it is possible to highlight deleterious synergistic comorbid conditions.Young adult cases with COVID-19 and co-existing diabetes, obesity, hypertension, CRF, or COPD were found more likely to have a fatal outcome compared with having no co-morbidities (X2-6 times). With the methodology proposed, we show that having diabetes or hypertension in addition to CRF increased risk for mortality more than what is expected from independent effect (adverse synergistic effect), whereas in patients with obesity, the additional presence of diabetes or hypertension do not increase markedly the death risk due to COVID-19. Quantitative analysis of having two comorbidities highlights the combinations of morbid conditions that are more likely to be associated with fatal outcomes in younger adults COVID-19 cases in a clinically applicable manner.The clinical implication of this method needs to be prospectively assessed.