bluuebunny/crossref_metadata_2025_split huggingface dataset:
DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality
Authors: Wudhikarn Kitsada , Pennisi Martina , Garcia-Recio Marta , Flynn Jessica R. , Afuye Aishat , Silverberg Mari Lynne , Maloy Molly A. , Devlin Sean M. , Batlevi Connie Lee , Shah Gunjan L. , Scordo Michael , Palomba Maria Lia , Dahi Parastoo B. , Sauter Craig S. , Santomasso Bianca D. , Mead Elena , Perales Miguel-Angel 
Published: July 2020

Abstract
Cytokine release syndrome (CRS) immune effector cell–associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell–mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade ≥2 and 289 grade ≥3 toxicities. Common grade ≥3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade ≥3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade ≥3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade ≥3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade ≥3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely associated with mortality. Our study emphasizes the importance of toxicity assessment, which could serve as a benchmark for further research to reduce symptom burdens and improve tolerability in patients treated with CAR T cells.
A cell-level quality control workflow for high-throughput image analysis
Authors: Qiu Minhua , Zhou Bin , Lo Frederick , Cook Steven , Chyba Jason , Quackenbush Doug , Matzen Jason , Li Zhizhong , Mak Puiying Annie , Chen Kaisheng , Zhou Yingyao 
Published: July 2020

Abstract
Background
Image-based high throughput (HT) screening provides a rich source of information on dynamic cellular response to external perturbations. The large quantity of data generated necessitates computer-aided quality control (QC) methodologies to flag imaging and staining artifacts. Existing image- or patch-level QC methods require separate thresholds to be simultaneously tuned for each image quality metric used, and also struggle to distinguish between artifacts and valid cellular phenotypes. As a result, extensive time and effort must be spent on per-assay QC feature thresholding, and valid images and phenotypes may be discarded while image- and cell-level artifacts go undetected.

Results
We present a novel cell-level QC workflow built on machine learning approaches for classifying artifacts from HT image data. First, a phenotype sampler based on unlabeled clustering collects a comprehensive subset of cellular phenotypes, requiring only the inspection of a handful of images per phenotype for validity. A set of one-class support vector machines are then trained on each biologically valid image phenotype, and used to classify individual objects in each image as valid cells or artifacts. We apply this workflow to two real-world large-scale HT image datasets and observe that the ratio of artifact to total object area (ARcell) provides a single robust assessment of image quality regardless of the underlying causes of quality issues. Gating on this single intuitive metric, partially contaminated images can be salvaged and highly contaminated images can be excluded before image-level phenotype summary, enabling a more reliable characterization of cellular response dynamics.

Conclusions
Our cell-level QC workflow enables identification of artificial cells created not only by staining or imaging artifacts but also by the limitations of image segmentation algorithms. The single readout ARcell that summaries the ratio of artifacts contained in each image can be used to reliably rank images by quality and more accurately determine QC cutoff thresholds. Machine learning-based cellular phenotype clustering and sampling reduces the amount of manual work required for training example collection. Our QC workflow automatically handles assay-specific phenotypic variations and generalizes to different HT image assays.
USMPep: universal sequence models for major histocompatibility complex binding affinity prediction
Authors: Vielhaben Johanna , Wenzel Markus , Samek Wojciech , Strodthoff Nils 
Published: July 2020

Abstract
Background
Immunotherapy is a promising route towards personalized cancer treatment. A key algorithmic challenge in this process is to decide if a given peptide (neoepitope) binds with the major histocompatibility complex (MHC). This is an active area of research and there are many MHC binding prediction algorithms that can predict the MHC binding affinity for a given peptide to a high degree of accuracy. However, most of the state-of-the-art approaches make use of complicated training and model selection procedures, are restricted to peptides of a certain length and/or rely on heuristics.

Results
We put forward USMPep, a simple recurrent neural network that reaches state-of-the-art approaches on MHC class I binding prediction with a single, generic architecture and even a single set of hyperparameters both on IEDB benchmark datasets and on the very recent HPV dataset. Moreover, the algorithm is competitive for a single model trained from scratch, while ensembling multiple regressors and language model pretraining can still slightly improve the performance. The direct application of the approach to MHC class II binding prediction shows a solid performance despite of limited training data.

Conclusions
We demonstrate that competitive performance in MHC binding affinity prediction can be reached with a standard architecture and training procedure without relying on any heuristics.
The regeneration of Acer rubrum L. “October Glory” through embryonic callus
Authors: Dai Chong-wen , Yan Yang-yang , Liu Yu-min , Liu Ya-min , Deng Yuan-wei , Yao Hong-yu 
Published: July 2020

Abstract
Background
Tissue culture and rapid propagation technology is an important way to solve the difficulties of plant propagation. This experiment aims to explore the appropriate conditions at each stage of the red maple’s tissue culture process and to obtain plantlets, thus providing a theoretical basis for the establishment of the red maple’s tissue culture system.

Results
The results showed that the stem segment is the most suitable explant for inducing embryogenic callus. The MS (Murashige&Skoog) + 0.8 mg/L TDZ (Thidiazuron) + 1.0 mg/L 6-BA (6-Benzylaminopurine) + 0.5 mg/L IAA(Indole-3-acetic acid) + 35 g/L sucrose+ 7.5 g/L semi-fixed medium was the best for callus formation. When selecting type VI callus as embryonic callus induction material, MS + 0.6 mg/L TDZ + 0.5 mg/L 6-BA + 2.0 mg/L IAA + 35 g/L sucrose+ 7.5 g/L semi-fixed medium can get embryonic callus. The optimal medium for adventitious bud induction is MS + 1.0 mg/L TDZ + 3.0 mg/L 6-BA+ 0.2 mg/L NAA (1-Naphthaleneacetic acid) + 1.2 mg/L IAA + 35 g/L sucrose+ 7.5 g/L semi-fixed medium. The induction rate of adventitious roots in MS + 0.6 mg/L TDZ + 1.0 mg/L 6-BA+ 3 mg/L NAA + 35 g/L sucrose+ 7.5 g/L semi-fixed medium was the highest, reaching 76%.

Conclusions
In the course of our research, we found that PGRs play an important role in the callus induction stage, and the effect of TDZ is particularly obvious; The callus cells grow and proliferate according to the “S” growth curve, and can be sub-cultured when the highest growth point is reached to maintain the rapid proliferation of the callus cells and to avoid inactivation of callus caused by tight niche.
Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction
Authors: Legallois Damien , Macquaire Clémence , Hodzic Amir , Allouche Stéphane , El Khouakhi Ismaïl , Manrique Alain , Milliez Paul , Saloux Eric , Beygui Farzin 
Published: July 2020

AbstractBackgroundLeft ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF).MethodsWe aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples.ResultsMedian age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL,n = 38], medium-level of neprilysin group [126–450 pg/mL,n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%,p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%,p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%,p = 0.55).ConclusionsInitial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.
Cognitive function of older adults engaging in physical activity
Authors: Ingold Monisha , Tulliani Nikki , Chan Chetwyn C. H. , Liu Karen P. Y. 
Published: July 2020

Abstract
Background
Physical activity can be classified as open-skilled or closed-skilled. Open-skilled physical activity, such as tennis, require participants to perform within a dynamic setting and respond to unpredictable and frequent environmental changes throughout the activity. Closed-skilled types of physical activity, such as swimming, are predictable and self-directed. However, the benefits of cognitive function in these two types of physical activities to older adults are unknown. This study examined the effects of participation in open- and closed-skilled physical activity on the cognitive function of older adults.

Methods
The study recruited a total of 61 participants aged 65 years and over. Participant recruitment was achieved by distributing flyers asking for volunteers in various sports venues. Participants self-reported to be without medical conditions affecting their physical and cognitive function. All participants underwent a two-hour assessment session involving the completion of seven standardised cognitive function assessments, which were used to assess a range of cognitive function.

Results
Overall mean scores across all of the assessments showed superior performance for the open- or closed-skilled participants when compared with the no-physical-activity group. The results of 61 adults who participated in this study showed that closed-skilled physical activity was associated with better selective attention and visuospatial function while open-skilled physical activity was associated with better inhibition and cognitive flexibility function. No significant difference in self-regulation ability was found between the open- or closed-skilled groups.

Conclusions
Open-skilled physical activity was associated with better inhibition, visual tracking, and cognitive flexibility while closed-skilled physical activity was associated with better selective attention and visuospatial perception. The findings have important practical implications for the health and quality of life of ageing populations, knowing which particular types of physical activity might affect the cognitive function.
Epidemiology and genetic diversity of circulating dengue viruses in Medellin, Colombia: a fever surveillance study
Authors: Lim Jacqueline Kyungah , Carabali Mabel , Camacho Erwin , Velez Diana Carolina , Trujillo Andrea , Egurrola Jorge , Lee Kang-Sung , Velez Ivan Dario , Osorio Jorge E. 
Published: July 2020

Abstract
Background
Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics.

Methods
In November 2011–February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10–21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing.

Results
Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage.

Conclusions
Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.
Angiotensin II receptor 1 antibodies associate with post-transplant focal segmental glomerulosclerosis and proteinuria
Authors: Abuzeineh Mohammad , Aala Amtul , Alasfar Sami , Alachkar Nada 
Published: July 2020

Abstract
Background
Angiotensin II type 1 receptors (AT1Rs) are expressed on podocytes, endothelial and other cells, and play an essential role in the maintenance of podocyte function and vascular homeostasis. The presence of AT1R antibodies (AT1R-Abs) leads to activation of these receptors resulting in podocyte injury and endothelial cell dysfunction. We assessed the correlation between AT1R-Abs and the risk of post-transplant FSGS.

Methods
This is a retrospective study, which included all kidney transplant recipients with positive AT1R-Abs (≥ 9 units/ml), who were transplanted and followed at our center between 2006 and 2016. We assessed the development of biopsy proven FSGS and proteinuria by urine protein to creatinine ratio of ≥1 g/g and reviewed short and long term outcomes.

Results
We identified 100 patients with positive AT1R-Abs at the time of kidney transplant biopsy or proteinuria. 49% recipients (FSGS group) had biopsy-proven FSGS and/or proteinuria and 51% did not (non-FSGS group). Pre-transplant hypertension was present in 89% of the FSGS group compared to 72% in the non-FSGS group, p = 0.027. Of the FSGS group, 43% were on angiotensin converting enzyme inhibitors or angiotensin receptor blockers prior to transplantation, compared to 25.5% in the non-FSGS group, p = 0.06. Primary idiopathic FSGS was the cause of ESRD in 20% of the FSGS group, compared to 6% in the non-FSGS group, p = 0.03. The allograft loss was significantly higher in the FSGS group 63% compared to 39% in non-FSGS. Odds ratio and 95% confidence interval were 2.66 (1.18–5.99), p = 0.017.

Conclusions
Our data suggest a potential association between AT1R-Abs and post-transplant FSGS leading to worse allograft outcome. Therefore, AT1R-Abs may be considered biomarkers for post-transplant FSGS.
Prevalence, associated factors and clinical features of congenital syphilis among newborns in Mbarara hospital, Uganda
Authors: Oloya Sam , Lyczkowski David , Orikiriza Patrick , Irama Max , Boum Yap , Migisha Richard , Kiwanuka Julius P. , Mwanga-Amumpaire Juliet 
Published: July 2020

Abstract
Background
While congenital syphilis is a significant public health problem that can cause severe disabilities, little is known about the situation in Uganda. We describe prevalence, associated factors and clinical presentation of congenital syphilis in Mbarara, Uganda.

Methods
A cross sectional study was carried out among mother- newborn dyads from the postnatal ward of Mbarara Regional Referral Hospital (MRRH). After obtaining informed consent, a structured questionnaire was used to capture data on risk factors for congenital syphilis. A finger prick was performed on the mothers for Treponema Pallidum Haemagglutination Assay (TPHA). If TPHA was positive, a venous blood sample was collected from the mother to confirm active infection using Rapid Plasma Reagin (RPR). Venous blood was drawn from a newborn if the mother tested positive by TPHA and RPR. A newborn with RPR titres 4 times higher than the mother was considered to have congenital syphilis. We fit logistic regression models to determine factors associated with congenital syphilis.

Results
Between June and September 2015, we enrolled 2500 mothers and 2502 newborns. Prevalence of syphilis was 3.8% (95% CI 3.1–4.6) among newborn infants and 4.1% (95% CI 3.4–5.0) among their mothers. Maternal age <25 years, past history of genital ulcer, a past history of abnormal vaginal discharge, and not receiving treatment of at least one of genital ulcer, genital itching, lower abdominal pain and abnormal vaginal discharge in the current pregnancy were the risk factors associated with congenital syphilis. The most common clinical feature was hepatosplenomegaly.

Conclusions
We found higher-than-expected syphilis sero-prevalence rates in a high risk population of postnatal mothers and their newborns in Uganda. Bridge populations for syphilis may include mothers not tested during pregnancy, who are usually married and not treated. In accordance with our results, the national policy for syphilis control in Uganda should be strengthened to include universal syphilis screening amongst mother-newborn pairs in postnatal clinics with subsequent partner notification.
Fluctuating expression of miR-584 in primary and high-grade gastric cancer
Authors: Ebrahimi Ghahnavieh Laleh , Tabatabaeian Hossein , Ebrahimi Ghahnavieh Zhaleh , Honardoost Mohammad Amin , Azadeh Mansoureh , Moazeni Bistgani Mohamad , Ghaedi Kamran 
Published: July 2020

AbstractBackgroundGastric cancer is the fifth most common cancer worldwide. Along with environmental factors, such asHelicobacter pylori(H. pylori) infection, genetic changes play important roles in gastric tumor formations. miR-584 is a less well-characterized microRNA (miRNA), with apparent activity in human cancers. However, miR-584 expression pattern in gastric cancer development has remained unclear. This study aims to analyze the expression of miR-584 in gastric cancer samples and investigates the associations between this miRNA andH. pyloriinfection and clinical characteristics.MethodsThe expression level of miR-584 was studied in primary gastric cancers versus healthy control gastric mucosa samples using the RT-qPCR method. The clinical data were analyzed statistically in terms of miR-584 expression.In silico studies were employed to study miR-584 more broadly in order to assess its expression and find new potential target genes.ResultsBoth experimental and in silico studies showed up-regulation of miR-584 in patients with gastric cancer. This up-regulation seems to be induced byH. pyloriinfection since the infected samples showed increased levels of miR-584 expression. Deeper analyses revealed that miR-584 undergoes a dramatic down-regulation in late stages, invasive and lymph node-metastatic gastric tumors. Bioinformatics studies demonstrated that miR-584 has a substantial role in cancer pathways and has the potential to target STAT1 transcripts. Consistent with the inverse correlation between TCGA RNA-seq data of miR-584 and STAT1 transcripts, the qPCR analysis showed a significant negative correlation between these two RNAs in a set of clinical samples.ConclusionmiR-584 undergoes up-regulation in the stage of primary tumor formation; however, becomes down-regulated upon the progression of gastric cancer. These findings suggest the potential of miR-584 as a diagnostic or prognostic biomarker in gastric cancer.
A predictive model for early diagnosis of keratoconus
Authors: Castro-Luna Gracia , Pérez-Rueda Antonio 
Published: July 2020

Abstract
Background
The diagnosis of keratoconus in the early stages of the disease is necessary to initiate an early treatment of keratoconus. Furthermore, to avoid possible refractive surgery that could produce ectasias. This study aims to describe the topographic, pachymetric and aberrometry characteristics in patients with keratoconus, subclinical keratoconus and normal corneas. Additionally to propose a diagnostic model of subclinical keratoconus based in binary logistic regression models.

Methods
The design was a cross-sectional study. It included 205 eyes from 205 patients distributed in 82 normal corneas, 40 early-stage keratoconus and 83 established keratoconus. The rotary Scheimpflug camera (Pentacam® type) analyzed the topographic, pachymetric and aberrometry variables. It performed a descriptive and bivariate analysis of the recorded data. A diagnostic and predictive model of early-stage keratoconus was calculated with the statistically significant variables.

Results
Statistically significant differences were observed when comparing normal corneas with early-stage keratoconus/ in variables of the vertical asymmetry to 90° and the central corneal thickness. The binary logistic regression model included the minimal corneal thickness, the anterior coma to 90° and posterior coma to 90°. The model properly diagnosed 92% of cases with a sensitivity of 97.59%, specificity 98.78%, accuracy 98.18% and precision 98.78%.

Conclusions
The differential diagnosis between normal cases and subclinical keratoconus depends on the mínimum corneal thickness, the anterior coma to 90° and the posterior coma to 90°.