bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and long-term outcomes of early gastric cardiac cancer treated with endoscopic submucosal dissection in 499 Chinese patients
Authors: Cao Shouli , Zou Tianhui , Sun Qi , Liu Tianyun , Fan Ting , Yin Qin , Fan Xiangshan , Jiang Jingwei , Raymond Dekusaah , Wang Yi , Zhang Bin , Lv Ying , Zhang Xiaoqi , Ling Tingsheng , Zhuge Yuzheng , Wang Lei , Zou Xiaoping , Xu Guifang , Huang Qin 
Published: October 2020

Aims: Early gastric cardiac cancer (EGCC) has a low risk of lymph node metastasis with the potential for endoscopic therapy. We aimed to evaluate the short- and long-term outcomes of endoscopic submucosal dissection (ESD)-resected EGCCs in a large cohort of Chinese patients and compare endoscopic and clinicopathologic features between EGCC and early gastric non-cardiac cancer (EGNC). Methods: We retrospectively studied 512 EGCCs in 499 consecutive patients and 621 EGNCs in 555 consecutive patients between January 2011 and March 2018 at our center. We investigated clinicopathological characteristics of EGCC tumors, ESD treatment results, adverse events, and postresection patient survival. Results: Compared with EGNC patients, EGCC patients were significantly older (average age: 66 years versus 62 years, p < 0.001). The percentage of the gross 0–IIc pattern was higher in EGCCs (46.1%) than in EGNCs (41.5%), while the frequency of the 0–IIa pattern was lower in EGCCs (14.9%) than in EGNCs (22.4%) ( p = 0.001). Compared with EGNCs, EGCCs showed smaller size, deeper invasion, fewer ulcerated or poorly differentiated tumors, but more cases with gastritis cystica profunda. The prevalence of ESD-related complications was higher in EGCCs (6.1%) than in EGNCs (2.3%) ( p = 0.001). In EGCCs, the disease-specific survival rate was significantly higher in patients of the noncurative resection group with surgery (100%), compared with that (93.9%) without surgery ( p < 0.001). Conclusion: Clinicopathological characteristics were significantly different between EGCCs and EGNCs. ESD is a safe and effective treatment option with favorable outcomes for patients with EGCC. Additional surgery improved survival in patients with noncurative ESD resection.
Pharmacokinetics in routine haemophilia clinical practice: rationale and modalities—a practical review
Authors: Hermans Cedric , Dolan Gerry 
Published: October 2020

Prophylactic therapy with exogenous clotting factor concentrates in haemophilia A and B aims to achieve levels of circulating FVIII or FIX that are adequate for the prevention or reduction of spontaneous joint bleeding. Historically, a minimum trough level of at least 1% of the normal levels of circulating clotting factor has been targeted using standardised protocols. However, clearance of clotting factor varies between products and patients, and other pharmacokinetic (PK) parameters such as the frequency and magnitude of peaks may be important for ensuring optimal coverage. Thus, it is increasingly recognised that an individualised, PK-based approach to prophylaxis is necessary to achieve optimal protection. This review focuses on the clinical implications of using PK-guided, individualised prophylaxis in haemophilia to improve patient outcomes and considers practical methods of establishing patients’ PK parameters. The most useful PK parameters will depend on the aim of the specific treatment (e.g. preventing activity-related and traumatic bleeds or addressing subclinical bleeding). In clinical practice, lengthy and frequent post-infusion sampling for PK analysis is costly and a significant burden for patients. However, a Bayesian analysis allows for the estimation of different PK parameters (e.g. half-life, factor concentrations over time, etc.) with only a minimum number of samples (e.g. 4, 24 and 48 h for haemophilia A), by using the patient’s data to adjust a relevant population PK value towards the actual value. Numerous tools are available to aid in the practical use of Bayesian PK-guided dosing in the clinic, including the Web-based Application for the Population Pharmacokinetic Service hosted by McMaster University, Canada. The PK data can be used to determine the appropriate prophylaxis regimen for the individual patient, which can be monitored by assessment of the trough level at each clinic visit. Collection of PK data and subsequent PK-guided dosing should become standard practice when determining treatment strategies for people with haemophilia.
Worse cardiovascular prognosis after endovascular surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes
Authors: Dakhel Ardwan , Zarrouk Moncef , Ekelund Jan , Acosta Stefan , Nilsson Peter , Miftaraj Mervete , Eliasson Björn , Svensson Ann-Marie , Gottsäter Anders 
Published: October 2020

Background: Diabetes mellitus (DM) is an established risk factor for intermittent claudication (IC) and other manifestations of atherosclerotic peripheral arterial disease. Indications for surgery in infrainguinal IC are debated, and there are conflicting reports regarding its outcomes in patients with DM. Aims of this study were to compare both short- and long-term effects on total- and cardiovascular (CV) mortality, major adverse cardiovascular events (MACEs), acute myocardial infarction (AMI), stroke, and major amputation following infrainguinal endovascular surgery for IC in patients with and without DM. We also evaluated potential relationships between diabetic control and outcomes in patients with DM. Methods: Nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Registry. Propensity score adjusted comparison of total and CV mortality, MACE, AMI, stroke, and major amputation after elective infrainguinal endovascular surgery for IC in 626 patients with and 1112 without DM at 30 postoperative days and after median 5.2 [interquartile range (IQR) 4.2–6.3] years of follow-up for patients with DM, and 5.4 (IQR 4.3–6.5) years for those without. Results: In propensity score adjusted Cox regression after 30 postoperative days, there were no differences between groups in morbidity or mortality. At last follow-up, patients with DM showed higher rates of MACE [hazard ratio (HR) 1.26, confidence interval (CI) 1.07–1.48; p < 0.01], AMI (HR 1.48, CI 1.09–2.00; p = 0.01), and major amputation (HR 2.31, CI 1.24–4.32; p < 0.01). Among patients with DM, higher HbA1c was associated with higher total mortality during follow-up (HR 1.01, CI 1.00–1.03; p = 0.045). Conclusion: Patients with DM have higher rates of MACE, AMI, and major amputation in propensity score adjusted analysis during 5 years of follow-up after infrainguinal endovascular surgery for IC. Furthermore, HbA1c is associated with total mortality in patients with DM. Prevention and treatment of DM is important to improve cardiovascular and limb outcomes.
Intrinsic functional connectivity alterations of the primary visual cortex in patients with proliferative diabetic retinopathy: a seed-based resting-state fMRI study
Authors: Yu Yao , Lan Dong-Yi , Tang Li-Ying , Su Ting , Li Biao , Jiang Nan , Liang Rong-Bin , Ge Qian-Min , Li Qiu-Yu , Shao Yi 
Published: October 2020

Purpose: In this study, we aimed to investigate the differences in the intrinsic functional connectivity (iFC) of the primary visual cortex (V1), based on resting-state functional magnetic resonance imaging (rs-fMRI), between patients with proliferative diabetic retinopathy (PDR) and healthy controls (HCs). Methods: In total, 26 patients (12 males, 14 females) with PDR and 26 HCs (12 males, 14 females), matched for sex, age, and education status, were enrolled in the study. All individuals underwent rs-fMRI scans. We acquired iFC maps and compared the differences between PDR patients and the HCs. Results: The PDR group had significantly increased FC between the left V1 and the right middle frontal gyrus (RMFG), and significantly reduced FC between the left V1 and the cuneus/calcarine/precuneus. In addition, the PDR patients had significantly increased FC between the right V1 and the right superior frontal gyrus (RSFG), and significantly reduced FC between the right V1 and the cuneus/calcarine/precuneus. The individual areas under the curve (AUCs) of FC values for the left V1 were as follows: RMFG (0.871, p < 0.001) and the cuneus/calcarine/precuneus (0.914, p < 0.001), while the AUCs of FC values for the right V1 were as follows: RSFG (0.895, p < 0.001) and the cuneus/calcarine/precuneus (0.918, p < 0.001). Conclusions: The results demonstrated that, in PDR patients, altered iFC in distinct brain regions, including regions related to visual information processing and cognition. Considering the rise in the diabetes mellitus incidence rate and the consequences of PDR, the results could provide promising clues for exploring the neural mechanisms related to PDR and possible approaches for the early identification of PDR.
Impact of a Hands-on Pre-Clinical Neurosurgery Elective Course on Second-Year Medical Student Interest and Attitudes
Authors: Sansosti Alexandra A , Jacobs Rachel C , Safonova Aleksandra , Jani Ronak H , Schumann Jack , Friedlander Robert M , Lunsford L Dade , McDowell Michael M , Sekula Raymond F 
Published: October 2020

Introduction: Medical student involvement opportunities and educational experiences with surgical residents during medical school have been shown to increase the chance of students deciding to specialize in surgical specialties. This study aims to determine the effect of a neurosurgery elective during the second preclinical year on student interest and opinion of neurosurgery. Methods: Thirty-nine students completed opinion-based surveys and factual knowledge quizzes during a neurosurgical elective course over 3 iterations, which included lecture and skills lab instruction. Pre- and post-course surveys used the Likert scale, with a score of 1 corresponding to the most negative opinion and a score of 10 corresponding to the most positive opinion, in order to measure various aspects including interest in neurological surgery, understanding of the field, and perception of female inclusion in the field. Weekly pre- and post-lecture quizzes assessed practical knowledge of neurosurgical topics. Results: A higher percentage of students rated neurosurgery highly as a career possibility (⩾8/10 interest level) post-course (58.6%) compared to pre-course (45.7%). Post-course, students reported a significantly increased mean understanding of neurosurgery on the Likert scale compared to pre-course (6.1 ± 1.7 vs 4.4 ± 2.0; P = .001). Knowledge based-content assessment revealed a significant increase in overall correct answers after lectures (meanpre = 3.85, meanpost = 5.05, P = .001). Inclusion of female instructors in the second and third iteration of the course resulted in a significant increase in students’ perception of female inclusion in the field of neurosurgery (7.6 compared to 5.6, P = .01). Conclusions: Early exposure to subspecialties may assist in making important career decisions. The implementation of this neurosurgical elective improved medical students’ perception of the field and enhanced knowledge of the lectures and procedures. This study can be used as a framework for implementation of this curriculum at other institutions.
del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma
Authors: Corre Jill , Perrot Aurore , Caillot Denis , Belhadj Karim , Hulin Cyrille , Leleu Xavier , Mohty Mohamad , Facon Thierry , Buisson Laure , Do Souto Laura , Lannes Romain , Dufrechou Stephanie , Prade Naïs , Orsini-Piocelle Frederique , Voillat Laurent , Jaccard Arnaud , Karlin Lionel , Macro Margaret , Brechignac Sabine , Dib Mamoun , Sanhes Laurence , Fontan Jean , Clement-Filliatre Lauriane , Marolleau Jean-Pierre , Minvielle Stephane , Moreau Philippe , Avet-Loiseau Hervé 
Published: October 2020

Abstract
Despite tremendous improvements in the outcome of patients with multiple myeloma in the past decade, high-risk patients have not benefited from the approval of novel drugs. The most important prognostic factor is the loss of parts of the short arm of chromosome 17, known as deletion 17p (del(17p)). A recent publication (on a small number of patients) suggested that these patients are at very high-risk only if del(17p) is associated with TP53 mutations, the so-called “double-hit” population. To validate this finding, we designed a much larger study on 121 patients presenting del(17p) in &gt; 55% of their plasma cells, and homogeneously treated by an intensive approach. For these 121 patients, we performed deep next generation sequencing targeted on TP53. The outcome was then compared with a large control population (2505 patients lacking del(17p)). Our results confirmed that the “double hit” situation is the worst (median survival = 36 months), but that del(17p) alone also confers a poor outcome compared with the control cohort (median survival = 52.8 months vs 152.2 months, respectively). In conclusion, our study clearly confirms the extremely poor outcome of patients displaying “double hit," but also that del(17p) alone is still a very high-risk feature, confirming its value as a prognostic indicator for poor outcome.
CDKAM: a taxonomic classification tool using discriminative k-mers and approximate matching strategies
Authors: Bui Van-Kien , Wei Chaochun 
Published: October 2020

Abstract
Background
Current taxonomic classification tools use exact string matching algorithms that are effective to tackle the data from the next generation sequencing technology. However, the unique error patterns in the third generation sequencing (TGS) technologies could reduce the accuracy of these programs.

Results
We developed a Classification tool using Discriminative K-mers and Approximate Matching algorithm (CDKAM). This approximate matching method was used for searching k-mers, which included two phases, a quick mapping phase and a dynamic programming phase. Simulated datasets as well as real TGS datasets have been tested to compare the performance of CDKAM with existing methods. We showed that CDKAM performed better in many aspects, especially when classifying TGS data with average length 1000–1500 bases.

Conclusions
CDKAM is an effective program with higher accuracy and lower memory requirement for TGS metagenome sequence classification. It produces a high species-level accuracy.
Cancer prognosis prediction using somatic point mutation and copy number variation data: a comparison of gene-level and pathway-based models
Authors: Zheng Xingyu , Amos Christopher I. , Frost H. Robert 
Published: October 2020

Abstract
Background
Genomic profiling of solid human tumors by projects such as The Cancer Genome Atlas (TCGA) has provided important information regarding the somatic alterations that drive cancer progression and patient survival. Although researchers have successfully leveraged TCGA data to build prognostic models, most efforts have focused on specific cancer types and a targeted set of gene-level predictors. Less is known about the prognostic ability of pathway-level variables in a pan-cancer setting. To address these limitations, we systematically evaluated and compared the prognostic ability of somatic point mutation (SPM) and copy number variation (CNV) data, gene-level and pathway-level models for a diverse set of TCGA cancer types and predictive modeling approaches.

Results
We evaluated gene-level and pathway-level penalized Cox proportional hazards models using SPM and CNV data for 29 different TCGA cohorts. We measured predictive accuracy as the concordance index for predicting survival outcomes. Our comprehensive analysis suggests that the use of pathway-level predictors did not offer superior predictive power relative to gene-level models for all cancer types but had the advantages of robustness and parsimony. We identified a set of cohorts for which somatic alterations could not predict prognosis, and a unique cohort LGG, for which SPM data was more predictive than CNV data and the predictive accuracy is good for all model types. We found that the pathway-level predictors provide superior interpretative value and that there is often a serious collinearity issue for the gene-level models while pathway-level models avoided this issue.

Conclusion
Our comprehensive analysis suggests that when using somatic alterations data for cancer prognosis prediction, pathway-level models are more interpretable, stable and parsimonious compared to gene-level models. Pathway-level models also avoid the issue of collinearity, which can be serious for gene-level somatic alterations. The prognostic power of somatic alterations is highly variable across different cancer types and we have identified a set of cohorts for which somatic alterations could not predict prognosis. In general, CNV data predicts prognosis better than SPM data with the exception of the LGG cohort.
Genomic differences between the new Fusarium oxysporum f. sp. apii (Foa) race 4 on celery, the less virulent Foa races 2 and 3, and the avirulent on celery f. sp. coriandrii
Authors: Henry Peter , Kaur Sukhwinder , Pham Quyen Anh Tran , Barakat Radwan , Brinker Samuel , Haensel Hannah , Daugovish Oleg , Epstein Lynn 
Published: October 2020

AbstractBackgroundMembers of theF. oxysporiumspecies complex (FOSC) in the f. sp.apii(Foa) are pathogenic on celery and those in f. sp.coriandrii(Foci) are pathogenic on coriander (=cilantro). Fociwas first reported in California in 2005; a new and highly aggressive race 4 ofFoawas observed in 2013 in California. Preliminary evidence indicated thatFoacan also cause disease on coriander, albeit are less virulent thanFoci. Comparative genomics was used to investigate the evolutionary relationships betweenFoarace 4,Foarace 3, and theFoci, which are all in FOSC Clade 2, andFoarace 2, which is in FOSC Clade 3.ResultsA phylogenetic analysis of 2718 single-copy conserved genes and mitochondrial DNA sequence indicated thatFoaraces 3 and 4 and theFociare monophyletic within FOSC Clade 2; these strains also are in a single somatic compatibility group. However, in the accessory genomes, theFociversusFoaraces 3 and 4 differ in multiple contigs. Based on significantly increased expression ofFoarace 4 genesin plantavs. in vitro, we identified 23 putative effectors and 13 possible pathogenicity factors. PCR primers for diagnosis of eitherFoarace 2 or 4 and theFociwere identified. Finally, mixtures of conidia that were pre-stained with different fluorochromes indicated thatFoarace 4 formed conidial anastomosis tubes (CATs) withFoci.Foarace 4 andFoarace 2, which are in different somatic compatibility groups, did not form CATs with each other.ConclusionsThere was no evidence thatFoarace 2 was involved in the recent evolution ofFoarace 4;Foarace 2 and 4 are CAT-incompatible. AlthoughFoaraces 3 and 4 and theFociare closely related, there is no evidence that eitherFocicontributed to the evolution ofFoarace 4, or thatFoarace 4 was the recent recipient of a multi-gene chromosomal segment from another strain. However, horizontal chromosome transfer could account for the major difference in the accessory genomes ofFoarace 4 and theFociand for their differences in host range.
Methylome and transcriptome profiles in three yak tissues revealed that DNA methylation and the transcription factor ZGPAT co-regulate milk production
Authors: Xin Jinwei , Chai Zhixin , Zhang Chengfu , Zhang Qiang , Zhu Yong , Cao Hanwen , Yangji Cidan , Chen Xiaoying , Jiang Hui , Zhong Jincheng , Ji Qiumei 
Published: October 2020

Abstract
Background
Domestic yaks play an indispensable role in sustaining the livelihood of Tibetans and other ethnic groups on the Qinghai-Tibetan Plateau (QTP), by providing milk and meat. They have evolved numerous physiological adaptations to high-altitude environment, including strong blood oxygen transportation capabilities and high metabolism. The roles of DNA methylation and gene expression in milk production and high-altitudes adaptation need further exploration.

Results
We performed genome-wide DNA methylome and transcriptome analyses of breast, lung, and biceps brachii muscle tissues from yaks of different ages. We identified 432,350 differentially methylated regions (DMRs) across the age groups within each tissue. The post-mature breast tissue had considerably more differentially methylated regions (155,957) than that from the three younger age groups. Hypomethylated genes with high expression levels might regulate milk production by influencing protein processing in the endoplasmic reticulum. According to weighted gene correlation network analysis, the “hub” gene ZGPAT was highly expressed in the post-mature breast tissue, indicating that it potentially regulates the transcription of 280 genes that influence protein synthesis, processing, and secretion. The tissue network analysis indicated that high expression of HIF1A regulates energy metabolism in the lung.

Conclusions
This study provides a basis for understanding the epigenetic mechanisms underlying milk production in yaks, and the results offer insight to breeding programs aimed at improving milk production.
Weighted gene coexpression network analysis-based identification of key modules and hub genes associated with drought sensitivity in rice
Authors: Yu Baiyang , Liu Jianbin , Wu Di , Liu Ying , Cen Weijian , Wang Shaokui , Li Rongbai , Luo Jijing 
Published: October 2020

Abstract
Background
Drought stress is an adverse factor with deleterious effects on several aspects of rice growth. However, the mechanism underlying drought resistance in rice remains unclear. To understand the molecular mechanism of the drought response in rice, drought-sensitive CSSL (Chromosome Single-substitution Segment Line) PY6 was used to map QTLs of sensitive phenotypes and to reveal the impact of the QTLs on transcriptional profiling.

Results
The QTL dss-1 was mapped onto the short arm of chromosome 1 of rice. According to transcriptomic analysis, the identified differentially expressed genes (DEGs) exhibited a downregulated pattern and were mainly enriched in photosynthesis-related GO terms, indicating that photosynthesis was greatly inhibited under drought. Further, according to weighted gene coexpression network analysis (WGCNA), specific gene modules (designating a group of genes with a similar expression pattern) were strongly correlated with H2O2 (4 modules) and MDA (3 modules), respectively. Likewise, GO analysis revealed that the photosynthesis-related GO terms were consistently overrepresented in H2O2-correlated modules. Functional annotation of the differentially expressed hub genes (DEHGs) in the H2O2 and MDA-correlated modules revealed cross-talk between abiotic and biotic stress responses for these genes, which were annotated as encoding WRKYs and PR family proteins, were notably differentially expressed between PY6 and PR403.

Conclusions
We speculated that drought-induced photosynthetic inhibition leads to H2O2 and MDA accumulation, which can then trigger the reprogramming of the rice transcriptome, including the hub genes involved in ROS scavenging, to prevent oxidative stress damage. Our results shed light on and provide deep insight into the drought resistance mechanism in rice.