bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer
Authors: Noman Abu Shadat M. , Parag Rashed R. , Rashid Muhammad I. , Rahman Mohammad Z. , Chowdhury Ali A. , Sultana Afrin , Jerin Chandsultana , Siddiqua Ayesha , Rahman Lutfur , Shirin Afsana , Nayeem Junayed , Mahmud Reaz , Akther Sonam , Shil Rajib K. , Hossain Ikram , Alam Sharmin , Chowdhury Arfina , Basher Shabnam B. , Hasan Abul , Bithy Shammy , Aklima Jannatul , Rahman Mizanur , Chowdhury Nabila , Banu Tahmina , Karakas Bedri , Yeger Herman , Farhat Walid A. , Islam Syed S. 
Published: March 2020

Background: Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs). Methods: We analyzed a cohort of patients with HNSCC to identify potential therapeutic biomarkers correlating with overall survival (OS) as well as disease-free survival (DFS) from our own data and validated these results using The Cancer Genome Atlas dataset. Expression of Shh and Nrf2 was knocked down by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated. Results: Widespread abundant expression of Shh and Nrf2 proteins were associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a significant predictor of patient DFS. The tumor stromal index was correlated with Shh expression and inversely associated with shorter OS and DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to the chemotherapeutic agents. Concomitant upregulation of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in patients with HNSCC. Conclusions: These findings suggest that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.
Prognostic value of respiratory index in haemodynamically stable patients with acute pulmonary embolism: The Respiratory Index model study
Authors: Vedovati Maria Cristina , Cimini Ludovica Anna , Pierpaoli Lucia , Vanni Simone , Cotugno Marilena , Pruszczyk Piotr , Di Filippo Francesco , Stefanone Valerio , Torrecillas Leticia Guirado , Kozlowska Marta , De Natale Maria Grazia , Mannucci Federica , Agnelli Giancarlo , Becattini Cecilia 
Published: March 2020

Background: Current strategies for prognostic stratification in haemodynamically stable patients with acute pulmonary embolism require improvement. The aims of this study in haemodynamically stable patients with acute pulmonary embolism were (a) to evaluate the prognostic value of a novel respiratory index (oxygen saturation in air to respiratory rate ratio) and (b) to derive a risk model which includes the respiratory index and evaluate its value in predicting 30-day mortality. Methods: Prospective cohorts of haemodynamically stable patients with acute pulmonary embolism were merged to a collaborative database that served to create two subsequent derivation and validation cohorts based on a temporal criterion. The study outcome was 30-day all-cause death. Results: Thirty-day all-cause death occurred in 7.5% and in 6.9% of patients in the derivation and validation cohorts (each composed of 319 patients). In the derivation cohort, the respiratory index (odds ratio 0.66, 95% confidence interval 0.48–0.90) and simplified Pulmonary Embolism Severity Index (odds ratio 9.16, 95% confidence interval 1.22–68.89) were predictors of 30-day mortality. The cut-off value of the respiratory index ⩽3.8 was identified to best predict 30-day all-cause death (15.4% vs 5.0%, odds ratio 2.94, 95% confidence interval 1.22–7.11). The respiratory index ⩽3.8 was combined with the simplified Pulmonary Embolism Severity Index to create the Respiratory Index model that showed a good discriminatory power in the derivation (c-statistic 0.703, 95% confidence interval 0.60–0.80) and in the validation cohort (c-statistic 0.838, 95% confidence interval 0.768–0.907). Conclusion: In hemodynamically stable patients with acute pulmonary embolism, the respiratory index was an independent predictor of 30-day all-cause death. The Respiratory Index model which includes the simplified Pulmonary Embolism Severity Index and the respiratory index, provides a good risk stratification of haemodynamically stable patients with acute pulmonary embolism.
Exploring Patients’ Insight, Concerns, and Expectations at Dermatology Clinic: An Observational Study in 2 Centers in Scotland and Spain
Authors: Martínez-García Eliseo , Affleck Andrew , Rakvit Pariyawan , Arias-Santiago Salvador , Buendía-Eisman Agustín 
Published: March 2020

Background: Effective doctor–patient communication is of great importance in order to optimize medical consultation outcomes. However, it can be difficult to address all patients’ concerns and expectations in clinic. Objective: To identify how much patients know about their medical condition, their fears and concerns, and their expectations, as well as evaluate the benefits of using a preconsultation questionnaire routinely. Methods: This study included consecutive patients attending dermatology outpatients from Dundee (Scotland) and Granada (Spain) who completed a simple preconsultation 3-part questionnaire. Answers to this questionnaire were discussed during clinic visits. Results: Two hundred patients participated in the study. Of all, 111 (55.5%) patients already knew their diagnosis or were able to describe their symptoms and/or feelings quite accurately at their visit to Dermatology. Most patients (85%) had fears regarding their dermatological problem. A majority of patients (97%) came to clinic with specific expectations, and many (41.5%) had multiple expectations. A high proportion of patients (74%) found the questionnaire useful. Conclusion: Patients attend clinic with different levels of knowledge, fears, and expectations. We recommend using a brief and easy to use preconsultation questionnaire as a cost-effective way of enhancing doctor–patient communication.
Dynamic incorporation of prior knowledge from multiple domains in biomarker discovery
Authors: Guan Xin , Runger George , Liu Li 
Published: March 2020

Abstract
Background
In biomarker discovery, applying domain knowledge is an effective approach to eliminating false positive features, prioritizing functionally impactful markers and facilitating the interpretation of predictive signatures. Several computational methods have been developed that formulate the knowledge-based biomarker discovery as a feature selection problem guided by prior information. These methods often require that prior information is encoded as a single score and the algorithms are optimized for biological knowledge of a specific type. However, in practice, domain knowledge from diverse resources can provide complementary information. But no current methods can integrate heterogeneous prior information for biomarker discovery. To address this problem, we developed the Know-GRRF (know-guided regularized random forest) method that enables dynamic incorporation of domain knowledge from multiple disciplines to guide feature selection.

Results
Know-GRRF embeds domain knowledge in a regularized random forest framework. It combines prior information from multiple domains in a linear model to derive a composite score, which, together with other tuning parameters, controls the regularization of the random forests model. Know-GRRF concurrently optimizes the weight given to each type of domain knowledge and other tuning parameters to minimize the AIC of out-of-bag predictions. The objective is to select a compact feature subset that has a high discriminative power and strong functional relevance to the biological phenotype.
Via rigorous simulations, we show that Know-GRRF guided by multiple-domain prior information outperforms feature selection methods guided by single-domain prior information or no prior information. We then applied Known-GRRF to a real-world study to identify prognostic biomarkers of prostate cancers. We evaluated the combination of cancer-related gene annotations, evolutionary conservation and pre-computed statistical scores as the prior knowledge to assemble a panel of biomarkers. We discovered a compact set of biomarkers with significant improvements on prediction accuracies.

Conclusions
Know-GRRF is a powerful novel method to incorporate knowledge from multiple domains for feature selection. It has a broad range of applications in biomarker discoveries. We implemented this method and released a KnowGRRF package in the R/CRAN archive.
Amazing symmetrical clustering in chloroplast genomes
Authors: Sadovsky Michael G. , Senashova Maria Yu , Malyshev Andrew V. 
Published: March 2020

Abstract
Background
Previously, a seven-cluster pattern claiming to be a universal one in bacterial genomes has been reported. Keeping in mind the most popular theory of chloroplast origin, we checked whether a similar pattern is observed in chloroplast genomes.

Results
Surprisingly, eight cluster structure has been found, for chloroplasts. The pattern observed for chloroplasts differs rather significantly, from bacterial one, and from that latter observed for cyanobacteria. The structure is provided by clustering of the fragments of equal length isolated within a genome so that each fragment is converted in triplet frequency dictionary with non-overlapping triplets with no gaps in frame tiling. The points in 63-dimensional space were clustered due to elastic map technique. The eight cluster found in chloroplasts comprises the fragments of a genome bearing tRNA genes and exhibiting excessively high GC-content, in comparison to the entire genome.

Conclusion
Chloroplasts exhibit very specific symmetry type in distribution of coding and non-coding fragments of a genome in the space of triplet frequencies: this is mirror symmetry. Cyanobacteria may have both mirror symmetry, and the rotational symmetry typical for other bacteria.
Robust pathway sampling in phenotype prediction. Application to triple negative breast cancer
Authors: Cernea Ana , Fernández-Martínez Juan Luis , deAndrés-Galiana Enrique J. , Fernández-Ovies Francisco Javier , Alvarez-Machancoses Oscar , Fernández-Muñiz Zulima , Saligan Leorey N. , Sonis Stephen T. 
Published: March 2020

AbstractBackgroundPhenotype prediction problems are usually considered ill-posed, as the amount of samples is very limited with respect to the scrutinized genetic probes. This fact complicates the sampling of the defective genetic pathways due to the high number of possible discriminatory genetic networks involved. In this research, we outline three novel sampling algorithms utilized to identify, classify and characterize the defective pathways in phenotype prediction problems, such as the Fisher’s ratio sampler, the Holdout sampler and the Random sampler, and apply each one to the analysis of genetic pathways involved in tumor behavior and outcomes of triple negative breast cancers (TNBC). Altered biological pathways are identified using the most frequently sampled genes and are compared to those obtained via Bayesian Networks (BNs).ResultsRandom, Fisher’s ratio and Holdout samplers were more accurate and robust than BNs, while providing comparable insights about disease genomics.ConclusionsThe three samplers tested are good alternatives to Bayesian Networks since they are less computationally demanding algorithms. Importantly, this analysis confirms the concept of “biological invariance” since the altered pathways should be independent of the sampling methodology and the classifier used for their inference. Nevertheless, still some modifications are needed in the Bayesian networks to be able to sample correctly the uncertainty space in phenotype prediction problems, since the probabilistic parameterization of the uncertainty space is not unique and the use of the optimum network might falsify the pathways analysis.
Applications of machine learning for simulations of red blood cells in microfluidic devices
Authors: Bachratý Hynek , Bachratá Katarína , Chovanec Michal , Jančigová Iveta , Smiešková Monika , Kovalčíková Kristína 
Published: March 2020

Abstract
Background
For optimization of microfluidic devices for the analysis of blood samples, it is useful to simulate blood cells as elastic objects in flow of blood plasma. In such numerical models, we primarily need to take into consideration the movement and behavior of the dominant component of the blood, the red blood cells. This can be done quite precisely in small channels and within a short timeframe. However, larger volumes or timescales require different approaches. Instead of simplifying the simulation, we use a neural network to predict the movement of the red blood cells.

Results
The neural network uses data from the numerical simulation for learning, however, the simulation needs only be run once. Alternatively, the data could come from video processing of a recording of a biological experiment. Afterwards, the network is able to predict the movement of the red blood cells because it is a system of bases that gives an approximate cell velocity at each point of the simulation channel as a linear combination of bases.In a simple box geometry, the neural network gives results comparable to predictions using fluid streamlines, however in a channel with obstacles forming slits, the neural network is about five times more accurate.The network can also be used as a discriminator between different situations. We observe about two-fold increase in mean relative error when a network trained on one geometry is used to predict trajectories in a modified geometry. Even larger increase was observed when it was used to predict trajectories of cells with different elastic properties.

Conclusions
While for uncomplicated box channels there is no advantage in using a system of bases instead of a simple prediction using fluid streamlines, in a more complicated geometry, the neural network is significantly more accurate. Another application of this system of bases is using it as a comparison tool for different modeled situations. This has a significant future potential when applied to processing data from videos of microfluidic flows.
Frailty assessment and risk prediction by GRACE score in older patients with acute myocardial infarction
Authors: Anand Atul , Cudmore Sarah , Robertson Shirley , Stephen Jacqueline , Haga Kristin , Weir Christopher J. , Murray Scott A. , Boyd Kirsty , Gunn Julian , Iqbal Javaid , MacLullich Alasdair , Shenkin Susan D. , Fox Keith A. A. , Mills Nicholas , Denvir Martin A. 
Published: March 2020

Abstract
Background
Risk prediction after myocardial infarction is often complex in older patients. The Global Registry of Acute Coronary Events (GRACE) model includes clinical parameters and age, but not frailty. We hypothesised that frailty would enhance the prognostic properties of GRACE.

Methods
We performed a prospective observational cohort study in two independent cardiology units: the Royal Infirmary of Edinburgh, UK (primary cohort) and the South Yorkshire Cardiothoracic Centre, Sheffield, UK (external validation). The study sample included 198 patients ≥65 years old hospitalised with type 1 myocardial infarction (primary cohort) and 96 patients ≥65 years old undergoing cardiac catheterisation for myocardial infarction (external validation). Frailty was assessed using the Clinical Frailty Scale (CFS). The GRACE 2.0 estimated risk of 12-month mortality, Charlson comorbidity index and Karnofsky disability scale were also determined for each patient.

Results
Forty (20%) patients were frail (CFS ≥5). These individuals had greater comorbidity, functional impairment and a higher risk of death at 12 months (49% vs. 9% in non-frail patients, p < 0.001). The hazard of 12-month all-cause mortality nearly doubled per point increase in CFS after adjustment for age, sex and comorbidity (Hazard Ratio [HR] 1.90, 95% CI 1.47–2.44, p < 0.001). The CFS had good discrimination for mortality by Receiver Operating Characteristic (ROC) curve analysis (Area Under the Curve [AUC] 0.81, 95% CI 0.72–0.89) and enhanced the GRACE estimate (AUC 0.86 vs. 0.80 without CFS, p = 0.04). At existing GRACE thresholds, the CFS resulted in a Net Reclassification Improvement (NRI) of 0.44 (95% CI 0.28–0.60, p < 0.001), largely through reductions in risk estimates amongst non-frail patients. Similar findings were observed in the external validation cohort (NRI 0.46, 95% CI 0.23–0.69, p < 0.001).

Conclusions
The GRACE score overestimated mortality risk after myocardial infarction in these cohorts of older patients. The CFS is a simple guided frailty tool that may enhance prediction in this setting. These findings merit evaluation in larger cohorts of unselected patients.

Trial registration
Clinicaltrials.gov; NCT02302014 (November 26th 2014, retrospectively registered).
Predictors of acute intracranial hemorrhage and recurrence of chronic subdural hematoma following burr hole drainage
Authors: Chen Fu Mei , Wang Ke , Xu Kang Li , Wang Li , Zhan Tian Xiang , Cheng Fei , Wang Hao , Chen Zuo-Bing , Gao Liang , Yang Xiao Feng 
Published: March 2020

Abstract
Background
To investigate predictors of postoperative acute intracranial hemorrhage (AIH) and recurrence of chronic subdural hematoma (CSDH) after burr hole drainage.

Methods
A multicenter retrospective study of patients who underwent burr hole drainage for CSDH between January 2013 and March 2019.

Results
A total of 448 CSDH patients were enrolled in the study. CSDH recurrence occurred in 60 patients, with a recurrence rate of 13.4%. The mean time interval between initial burr hole drainage and recurrence was 40.8 ± 28.3 days. Postoperative AIH developed in 23 patients, with an incidence of 5.1%. The mean time interval between initial burr hole drainage and postoperative AIH was 4.7 ± 2.9 days. Bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independent predictors of recurrence in the multiple logistic regression analyses. Preoperative headache was an independent risk factor of postoperative AIH in the multiple logistic regression analyses, however, intraoperative irrigation reduced the incidence of postoperative AIH.

Conclusions
This study found that bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independently associated with CSDH recurrence. Clinical presentation of headache was the strongest predictor of postoperative AIH, and intraoperative irrigation decreased the incidence of postoperative AIH.
Sustained HIV viral suppression among men who have sex with men in the Miami-Dade County Ryan White Program: the effect of demographic, psychosocial, provider and neighborhood factors
Authors: Sheehan Diana M. , Dawit Rahel , Gbadamosi Semiu O. , Fennie Kristopher P. , Li Tan , Gebrezgi Merhawi , Brock Petra , Ladner Robert A. , Trepka Mary Jo 
Published: March 2020

Abstract
Background
HIV viral suppression is associated with health benefits for people living with HIV and a decreased risk of HIV transmission to others. The objective was to identify demographic, psychosocial, provider and neighborhood factors associated with sustained viral suppression among gay, bisexual, and other men who have sex with men.

Methods
Data from adult men who have sex with men (MSM) enrolled in the Miami-Dade County Ryan White Program (RWP) before 2017 were used. Sustained viral suppression was defined as having an HIV viral load < 200 copies/ml in all viral load tests in 2017. Three-level (individual, medical case management site, and neighborhood) cross-classified mixed-effect models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for sustained viral suppression.

Results
Of 3386 MSM, 90.8% were racial/ethnic minorities, and 84.4% achieved sustained viral suppression. The odds of achieving sustained viral suppression was lower for 18–24 and 25–34 year-old MSM compared with 35–49 year-old MSM, and for non-Latino Black MSM compared with White MSM. Those not enrolled in the Affordable Care Act, and those with current AIDS symptoms and a history of AIDS had lower odds of achieving sustained viral suppression. Psychosocial factors significantly associated with lower odds of sustained viral suppression included drug/alcohol use, mental health symptoms, homelessness, and transportation to appointment needs. Individuals with an HIV physician who serves a larger volume of RWP clients had greater odds of sustained viral suppression. Neighborhood factors were not associated with sustained viral suppression.

Conclusion
Despite access to treatment, age and racial disparities in sustained viral suppression exist among MSM living with HIV. Addressing substance use, mental health, and social services’ needs may improve the ability of MSM to sustain viral suppression long-term. Furthermore, physician characteristics may be associated with HIV outcomes and should be explored further.
Oral management of a patient with down syndrome and agammaglobulinemia: a case report
Authors: Kusumoto Yasuka , Imai Kohsuke , Ohyama Yoshio , Fukayama Haruhisa , Shinozuka Osamu 
Published: March 2020

AbstractBackgroundDown syndrome is characterized by a variety of dysmorphic features and congenital malformations, such as congenital heart disease, gastrointestinal disease, and other conditions like leukemia and autoimmune disorders. Patients with Down syndrome are highly prone to respiratory tract infections, which might be fatal to them. However, there are only few available data on patients diagnosed with Down syndrome and agammaglobulinemia. In this report, we describe a case of successful prevention of post-dental treatment complications (e.g., pneumonia and other bacterial infections) in a patient with Down syndrome and agammaglobulinemia.Case presentationA 43-year-old man with Down syndrome, untreated agammaglobulinemia, and a history of recurrent pneumonia, was referred to our clinic for tooth mobility. To reduce the risk of post-operative infections, gammaglobulin treatment and prophylactic administration of antibiotics was scheduled before the dental procedure. Furthermore, the dental treatment, which included a filling and extractions, was conducted under general anesthesia and with the supervision of a hematologist. The dental procedures were successfully performed without any post-operative infection, and the patient is undergoing follow-up care.ConclusionsThe purpose of this case report was to recommend a close liaison between physicians and dentists who may encounter a similar case, and to emphasize the importance of improving oral health of immunodeficient patients to prevent infections caused by oral microbial flora.