bluuebunny/crossref_metadata_2025_split huggingface dataset:
LANDMark: an ensemble approach to the supervised selection of biomarkers in high-throughput sequencing data
Authors: Rudar Josip , Porter Teresita M. , Wright Michael , Golding G. Brian , Hajibabaei Mehrdad 
Published: March 2022

AbstractBackgroundIdentification of biomarkers, which are measurable characteristics of biological datasets, can be challenging. Although amplicon sequence variants (ASVs) can be considered potential biomarkers, identifying important ASVs in high-throughput sequencing datasets is challenging. Noise, algorithmic failures to account for specific distributional properties, and feature interactions can complicate the discovery of ASV biomarkers. In addition, these issues can impact the replicability of various models and elevate false-discovery rates. Contemporary machine learning approaches can be leveraged to address these issues. Ensembles of decision trees are particularly effective at classifying the types of data commonly generated in high-throughput sequencing (HTS) studies due to their robustness when the number of features in the training data is orders of magnitude larger than the number of samples. In addition, when combined with appropriate model introspection algorithms, machine learning algorithms can also be used to discover and select potential biomarkers. However, the construction of these models could introduce various biases which potentially obfuscate feature discovery.ResultsWe developed a decision tree ensemble, LANDMark, which uses oblique and non-linear cuts at each node. In synthetic and toy tests LANDMark consistently ranked as the best classifier and often outperformed the Random Forest classifier. When trained on the full metabarcoding dataset obtained from Canada’s Wood Buffalo National Park, LANDMark was able to create highly predictive models and achieved an overall balanced accuracy score of 0.96 ± 0.06. The use of recursive feature elimination did not impact LANDMark’s generalization performance and, when trained on data from the BE amplicon, it was able to outperform the Linear Support Vector Machine, Logistic Regression models, and Stochastic Gradient Descent models (p ≤ 0.05). Finally, LANDMark distinguishes itself due to its ability to learn smoother non-linear decision boundaries.ConclusionsOur work introduces LANDMark, a meta-classifier which blends the characteristics of several machine learning models into a decision tree and ensemble learning framework. To our knowledge, this is the first study to apply this type of ensemble approach to amplicon sequencing data and we have shown that analyzing these datasets using LANDMark can produce highly predictive and consistent models.
classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes
Authors: Quinn Gerard P. , Sessler Tamas , Ahmaderaghi Baharak , Lambe Shauna , VanSteenhouse Harper , Lawler Mark , Wappett Mark , Seligmann Bruce , Longley Daniel B. , McDade Simon S. 
Published: March 2022

AbstractBackgroundTranscriptionally informed predictions are increasingly important for sub-typing cancer patients, understanding underlying biology and to inform novel treatment strategies. For instance, colorectal cancers (CRCs) can be classified into four CRC consensus molecular subgroups (CMS) or five intrinsic (CRIS) sub-types that have prognostic and predictive value. Breast cancer (BRCA) has five PAM50 molecular subgroups with similar value, and the OncotypeDX test provides transcriptomic based clinically actionable treatment-risk stratification. However, assigning samples to these subtypes and other transcriptionally inferred predictions is time consuming and requires significant bioinformatics experience. There is no "universal" method of using data from diverse assay/sequencing platforms to provide subgroup classification using the established classifier sets of genes (CMS, CRIS, PAM50, OncotypeDX), nor one which in provides additional useful functional annotations such as cellular composition, single-sample Gene Set Enrichment Analysis, or prediction of transcription factor activity.ResultsTo address this bottleneck, we developed classifieR, an easy-to-use R-Shiny based web application that supports flexible rapid single sample annotation of transcriptional profiles derived from cancer patient samples form diverse platforms. We demonstrate the utility of the " classifieR" framework to applications focused on the analysis of transcriptional profiles from colorectal (classifieRc) and breast (classifieRb). Samples are annotated with disease relevant transcriptional subgroups (CMS/CRIS sub-types in classifieRc and PAM50/inferred OncotypeDX in classifieRb), estimation of cellular composition using MCP-counter and xCell, single-sample Gene Set Enrichment Analysis (ssGSEA) and transcription factor activity predictions with Discriminant Regulon Expression Analysis (DoRothEA).ConclusionsclassifieR provides a framework which enables labs without access to a dedicated bioinformation can get information on the molecular makeup of their samples, providing an insight into patient prognosis, druggability and also as a tool for analysis and discovery. Applications are hosted online athttps://generatr.qub.ac.uk/app/classifieRcandhttps://generatr.qub.ac.uk/app/classifieRbafter signing up for an account onhttps://generatr.qub.ac.uk.
Context-dependent DNA polymerization effects can masquerade as DNA modification signals
Authors: Takahashi Yusuke , Shoura Massa , Fire Andrew , Morishita Shinichi 
Published: March 2022

Abstract
Background
Single molecule measurements of DNA polymerization kinetics provide a sensitive means to detect both secondary structures in DNA and deviations from primary chemical structure as a result of modified bases. In one approach to such analysis, deviations can be inferred by monitoring the behavior of DNA polymerase using single-molecule, real-time sequencing with zero-mode waveguide. This approach uses a Single Molecule Real Time (SMRT)-sequencing measurement of time between fluorescence pulse signals from consecutive nucleosides incorporated during DNA replication, called the interpulse duration (IPD).

Results
In this paper we present an analysis of loci with high IPDs in two genomes, a bacterial genome (E. coli) and a eukaryotic genome (C. elegans). To distinguish the potential effects of DNA modification on DNA polymerization speed, we paired an analysis of native genomic DNA with whole-genome amplified (WGA) material in which DNA modifications were effectively removed. Adenine modification sites for E. coli are known and we observed the expected IPD shifts at these sites in the native but not WGA samples. For C. elegans, such differences were not observed. Instead, we found a number of novel sequence contexts where IPDs were raised relative to the average IPDs for each of the four nucleotides, but for which the raised IPD was present in both native and WGA samples.

Conclusion
The latter results argue strongly against DNA modification as the underlying driver for high IPD segments for C. elegans, and provide a framework for separating effects of DNA modification from context-dependent DNA polymerase kinetic patterns inherent in underlying DNA sequence for a complex eukaryotic genome.
Impacts of autofluorescence on fluorescence based techniques to study microglia
Authors: Zhang Haozhe , Tan Chen , Shi Xiaoyue , Xu Ji 
Published: March 2022

Abstract
Background
Microglia, the resident immune cells in the central nervous system, accrue autofluorescent granules inside their cytoplasm throughout their lifespan. In this report, we studied the impacts of autofluorescence on widely used fluorescence-based techniques to study microglia, including flow cytometry, immunofluorescence staining, and live imaging.

Results
The failed attempt of using fluorescein isothiocyanate (FITC) conjugated antibody to detect lymphocyte-activation gene 3 protein in microglia prompted us to compare the sensitivity of FITC, phycoerythrin (PE) and allophycocyanin (APC) conjugated antibodies to detect surface protein expression in microglia. We found that PE outperformed FITC and APC as the fluorophore conjugated to antibody for flow cytometry by overcoming the interference from microglia autofluorescence. To identify the location and source of microglia autofluorescence, we did confocal imaging and spectral analysis of microglia autofluorescence on fixed brain tissues, revealing that microglia autofluorescence emitted from cytoplasmic granules and displayed a multi-peak emission spectrum. We recommended removing autofluorescence by lipofuscin removing agents when staining intracellular proteins in microglia with the immunofluorescence techniques. On live brain slices, autofluorescent granules reduced the amplitudes of calcium signals in microglial somata derived from GCaMP6s fluorescence and thus needed to be excluded when selecting regions of interest (ROI).

Conclusions
In conclusion, autofluorescence is a critical factor to consider when designing experiments and interpreting results based on fluorescence-based techniques to study microglia.
Comparison of fibrosing mediastinitis patients with vs. without markedly increased systolic pulmonary arterial pressure: a single-center retrospective study
Authors: Zhang Xinyuan , Zhang Shu , Wang Jianfeng , Jiang Wei , Sun Lanlan , Li Yuanzhi , Guo Dichen , Yang Yuanhua , Lu Xiuzhang , Li Yidan 
Published: March 2022

Abstract
Introduction
Fibrosing mediastinitis (FM) complicated with pulmonary hypertension (PH) has been considered as an important cause of morbidity and mortality. This study was designed to observe the possible effects of abnormal hemodynamics on patients by conducting a between-group comparison according to the presence of markedly increased systolic pulmonary arterial pressure (SPAP), so as to provide more information for clinical management.

Materials and methods
Fifty-one patients with clinically diagnosed FM were divided in two groups (SPAP < 50 mmHg group; SPAP ≥ 50 mmHg group) and retrospectively included in the study. Data mainly including demographic factors, echocardiographic data, results of right heart catheter and computed tomography (CT) examination were retrieved from the medical database. Echocardiographic parameters pre- and post- balloon pulmonary angioplasty (BPA) treatment were also collected in 8 patients.

Results
Significant changes in cardiac structure, hemodynamics and cardiac function were detected in patients complicated with markedly increased SPAP. Patients in the SPAP ≥ 50 mmHg group had increased right heart diameter, right heart ratio and velocity of tricuspid regurgitation (VTR) (p < 0.05). Deteriorated right heart function was also observed. There was no significant difference in CT findings between the two groups, except that more patients in the SPAP ≥ 50 mmHg group had pleural effusion (p < 0.05). After primary BPA in 8 patients, improvement in the right atrium proportion was observed.

Conclusions
Changes due to significantly increased SPAP in patients with FM include adverse structure and function of the right heart, but differences in CT findings were not significant. Echocardiography has advantages as a noninvasive tool for the evaluation of cardiac structure, function and hemodynamics in patients with FM.
Preprocedural and procedural variables that predict new-onset conduction disturbances after transcatheter aortic valve replacement
Authors: Boonyakiatwattana Wongsaput , Maneesai Adisak , Chaithiraphan Vithaya , Jakrapanichakul Decho , Sakiyalak Pranya , Chunhamaneewat Narathip , Slisatkorn Worawong , Chotinaiwattarakul Chunhakasem , Pongakasira Rungtiwa , Wongpraparut Nattawut 
Published: March 2022

Abstract
Background
Conduction disturbances are a common complication after transcatheter aortic valve replacement (TAVR). The aim of this study was to investigate the preprocedural and procedural variables that predict new-onset conduction disturbances post-TAVR (hereafter CD/CDs).

Methods
Consecutive patients who underwent TAVR during December 2009–March 2021 at the Faculty of Medicine Siriraj Hospital, Mahidol University—Thailand’s largest national tertiary referral center—were enrolled. Patients with prior implantation of a cardiac device, periprocedural death, or unsuccessful procedure were excluded. Clinical and electrocardiographic data, preprocedural imaging, including membranous septum (MS) length, and procedural variables, including implantation depth (ID), were analyzed. CD was defined as new left or right bundle branch block, significant intraventricular conduction disturbance with QRS interval ≥ 120 ms, new high-grade atrioventricular block, or complete heart block. Multivariate binary logistic analysis and receiver operating characteristic (ROC) curve analysis were used to identify independent predictors and the optimal ∆MSID (difference between the MS length and ID) cutoff value, respectively.

Results
A total of 124 TAVR patients (mean age: 84.3 ± 6.3 years, 62.1% female) were included. The mean Society of Thoracic Surgeons score was 7.3%, and 85% of patients received a balloon expandable transcatheter heart valve. Thirty-five patients (28.2%) experienced a CD, and one-third of those required pacemaker implantation. The significant preprocedural and procedural factors identified from univariate analysis included intraventricular conduction delay, mitral annular calcification, MS length ≤ 6.43 mm, self-expanding device, small left ventricular cavity, and ID ≥ 6 mm. Multivariate analysis revealed MS length ≤ 6.43 mm (adjusted odds ratio [aOR] 9.54; 95% CI 2.56–35.47; p = 0.001) and ∆MSID < 0 mm (adjusted odds ratio [aOR] 10.77; 95% CI 2.86–40.62; p =  < 0.001) to be independent predictors of CD. The optimal ∆MSID cutoff value for predicting conduction disturbances was less than 0 mm (area under the receiver operating characteristic curve [AuROC]: 0.896).

Conclusion
This study identified MS length ≤ 6.43 mm and ∆MSID < 0 mm as independent predictors of CDs. ∆MSID < 0 was the strongest and only modifiable predictor. Importantly, we expanded the CD criteria to cover all spectrum of TAVR-related conduction injury to lower the threshold of this sole modifiable risk. The optimal ∆MSID cutoff value was < 0 mm.
Trial registration: TCTR, TCTR20210818002. Registered 17 August 2021—Retrospectively registered, http://www.thaiclinicaltrials.org/show/TCTR 20210818002.
Implementation and findings on a one-minute sit-stand test for prehospital triage in patients with suspected COVID-19—a pilot project
Authors: Kjerulff Julie , Bach Allan , Væggemose Ulla , Skaarup Søren Helbo , Bøtker Morten Thingemann 
Published: March 2022

AbstractIntroductionDuring the initial Coronavirus Disease 2019 (COVID-19) pandemic wave, sparse personal protection equipment made telephone triage of suscpeted COVID-19 patients for ambulance transport necessary. To spare resources, stable patients were often treated and released on-scene, but reports from Italy suggested that some later detoriated. We implemented a prehospital sit-stand test to identify patients in risk for detoriation.MethodsThe test was implemented as part of a new guideline in stable suspected COVID-19 patients younger than 70 years with no risk factors for serious disease triaged by general practitioners to ambulance response in the Central Denmark Region. Data were collected from April 6thto July 6th2020. The primary outcome for this study was the proportion of patients treated with oxygen within 7 days among patients decompensating vs patients not decompensating during the test.ResultsData on 156 patients triaged to ambulance response by general practioners were analysed. In total 86/156 (55%) were tested with the sit-stand test. Due to off-guideline use of the test, 30/86 (34.8%) were either older than 70 or had risk factors for serious disease. 10/156 (6%) of patients had a positive COVID-19-test. In total, 17/86 (20%) decompensated during the test and of these, 9/17 (53%) were treated with oxygen compared to 2/69 (3%) in patients who did not decompensate (p < 0.001).ConclusionIn a population suspected of COVID-19 but with a low COVD-19 prevalence, decompensation with the sit-stand test was observed in 20% of patients and was associated with oxygen treatment within 7 days. These findings are hypotheses-generating and suggest that physical exercise testing may be usefull for decision making in emergency settings.
Epidemiology, injury characteristics and clinical outcomes of bicycle and motorcycle accidents in the under 20 population: South Korea
Authors: Yun Hyeokmin , Bae Sung Jin , Lee Jung Il , Lee Duk Hee 
Published: March 2022

Abstract
Background
Bicycles and motorcycles are a main means of transportation and leisure for individuals aged under 20 years in South Korea. We aimed to identify the epidemiology of injuries and describe and compare patterns of injury and clinical outcomes of two-wheel vehicle-related accidents in these individuals.

Methods
We analysed data obtained from the National Emergency Department Information System for 401 emergency departments (EDs) from January 2016 to December 2018. We included patients aged < 20 years who experienced injuries while driving or a passenger on two-wheeled vehicles. We analysed patients with a bicycle-related injury and those with a motorcycle-related injury, and then compared two groups and performed a regression analysis for factors predicting severe trauma.

Results
This study enrolled 54,342 two-wheel vehicle injury patients (37,410 bicycle and 16,932 motorcycle-related), of which, 86.8% (bicycle) and 94.9% (motorcycle) were males. External injuries were the most common. ED mortality was 9 (0.0%) for bicycles and 53 (0.3%) for motorcycles.
Overall, 3,346 (8.9%) patients were hospitalised with bicycle injuries and 4,096 (24.2%) with motorcycle injuries. Among admitted patients with bicycle-related injuries, 48.7% had upper extremity injuries and among those admitted patients with motorcycle-related injuries, 76.0% had lower extremity injuries.
Among hospitalised patients, the mean injury severity score (ISS) was 12.0 ± 12.6 in bicycle-related injury and 17.6 ± 15.4 in motorcycle-related injury. The number of patients with ISS ≥ 16 was 27.6% for bicycle related injuries and 45.2% for motorcycle-related injuries. The mean length of hospital stay was 191.5.8 ± 224.2 h for bicycle injury, and 359.6 ± 416.7 h for motorcycles. Hospital mortality cases were 0.2% with bicycle injury and 1.2% with motorcycle injury. Motorcycle-related injuries had more severe injury (ISS ≥ 16), with an adjusted odds ratio of 2.825 (95% confidence interval 2.610–3.059) compared to bicycle-related injuries.

Conclusions
In the population aged under 20 years, two-wheel vehicle-related occurred predominantly in males. When using two-wheeled vehicles, motorcycle injuries were higher in patients aged over 14 years and were associated with higher ISS (≥ 16). Political efforts should be made to educate under 20 years of age for safe driving and to wear protective gear, including helmets to prevent severe injury.
Burden of respiratory syncytial virus-associated lower respiratory infections in children in Spain from 2012 to 2018
Authors: Heppe-Montero Marco , Walter Stefan , Hernández-Barrera Valentín , Gil-Prieto Ruth , Gil-de-Miguel Ángel 
Published: March 2022

Abstract
Background
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection (ALRI) leading to infant hospitalization, morbidity and postnatal mortality in children younger than 5 years of age worldwide. The aim of this study was to collect data on hospitalizations for RSV-related ALRI in children in Spain from 2012 to 2018.

Methods
We used the discharge reports from the Minimum Basic Data Set (MBDS) to retrospectively analyze hospital discharge data in children ≤ 14 years of age with a diagnosis of acute lower respiratory tract infection, based on the ICD-9-CM and ICD-10-CM diagnosis codes, from 2012 to 2018.

Results
A total of 190,474 children, 58.1% boys and 41.9% girls, were admitted for lower respiratory tract infections in Spain, including 118,731 cases of bronchiolitis, 53,972 cases of bronchitis, 3710 cases of RSV-positive pneumonia, and 14,061 cases of RSV infections. Of these, 92,426 children (48.5%) had laboratory-confirmed RSV infection. The mean case fatality rate was almost 6 times higher for pneumonia (0.6%) than for bronchiolitis (0.1%) or bronchitis (0.1%). A significant linear increase in the mean annual hospitalization rate for pneumonia of almost 15% per year was found, with no changes in the trend over the study period.

Conclusions
RSV-related respiratory infections remain a leading cause of infant hospitalization in Spain. Effective antiviral treatments and preventive vaccines are urgently needed for the management of RSV infection in children, especially for those aged 6 to 12 months.
Value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission: a case report and literature review
Authors: Zhang Ping , Chen Xiuling , Zou Yurong , Wang Wei , Feng Yunlin 
Published: March 2022

Abstract
Backgrounds
Published literatures on repeat renal biopsy of AL amyloidosis have basically reached a consensus that amyloid material deposit does not disappear or diminish after satisfactory hematologic response, regardless of renal response. However, the need of a repeat renal biopsy in such situation is still controversial.

Case presentation
Here we reported a case of histologically confirmed λ Type renal AL amyloidosis who had been classified as Stage I and low risk at initial diagnosis. The patient received a total of six courses of CyBorD chemotherapy. She had achieved complete hematologic remission after two courses of chemotherapy but consistently had large amount of proteinuria over 10 g/day during follow up. A repeat renal biopsy was performed nine months after the first one and indicated mild to moderate increase of amyloid deposits as well as significant glomerulosclerosis and interstitial lesions, suggesting a lack of histological renal improvement despite her satisfactory hematologic response.

Conclusions
This case indicated renal involvement in AL amyloidosis could progress after successful hematologic treatment, and supported the value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission.