bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spine-Related Malpractice Claims in China: A 2-year National Analysis
Authors: Yue Lei , Sun Ming-Shuai , Mu Guan-Zhang , Shang Mei-Xia , Zhang Ying-Ze , Sun Hao-Lin , Li Chun-De 
Published: September 2021

Study design Retrospective cross-sectional study. Objective To investigate the prevalence, characteristics, and risk factors of spine-related malpractice claims in China in a 2-year period. Methods The arbitration files of the Chinese Medical Association (CMA) were reviewed for spine-related malpractice claims. Descriptive statistics and correlation analysis were conducted on claim characteristics, clinical data, plaintiff’s main allegations, and arbitration outcomes. Results A total of 288 cases of spinal claims filed in the CMA between January 2016 and December 2017 were included. Most claims were found in lumbar degenerative disorders (59.4%), lumbar trauma (13.2%), and cervical degenerative disorders (11.8%). The most common adverse events (AEs) leading to claims were new neurologic deficit (NND) (47.6%), infection (11.5%), and insufficient symptom relief (10.4%). The most common patient allegation was surgical error (66.0%), although the main arbitrated cause of AEs was disease/treatment itself (49.0%), while providers were judged as mainly responsible in only 47.3% cases. In multivariate regression analysis, cervical spine, misdiagnosis/mistreatment, and unpredictable emergency correlated with more severe damage to patients; minimally invasive surgery was predictive of judgment in plaintiff’s favor, while claims in the eastern region and unpredictable emergencies were predictive of defendant’s favor; only NND was associated with being arbitrated as surgical error in surgical cases where surgeons accepted major liability. Conclusion The current study provided a descriptive overview and risk factor analysis of spine-related malpractice claims in China. Gaining improved understanding of the facts and causes of malpractice claims may help providers reduce the risk of claims and subsequent litigation.
What Helps, What Hinders? Undergraduate Nursing Students’ Perceptions of Clinical Placements Based on a Thematic Synthesis of Literature
Authors: Cant Robyn , Ryan Colleen , Hughes Lynda , Luders Elise , Cooper Simon 
Published: September 2021

Introduction Clinical placements are a mandatory component of nursing students’ education internationally. Despite clinical education being a key to nursing students’ achievement of nursing competencies, few studies have reviewed students’ narratives to describe their experiences of learning during clinical placement. Such studies may be important in offering a deeper insight into clinical learning experiences than quantitative surveys. Methods A systematic thematic synthesis of qualitative studies between 2010 and June 2020 was conducted. English language studies that offered a thematic analysis of undergraduate nursing students’ experiences of learning during placement were sought. A search was made of five databases PubMed, Ovid Medline, CinahlPlus, SCOPUS, and Google Scholar. The study was guided by the ENTREQ statement for enhancing transparency in reporting the synthesis of qualitative research. Results Twenty-seven qualitative studies were included in the review. A thematic synthesis showed over 100 themes and subthemes across the studies. A cluster analysis revealed positive elements and others that were seen in the studies as a barrier (hindrance) to clinical learning. Positive elements included supportive instructors, close supervision, and belonging (in the team). Unsupportive instructors, a lack of supervision and not being included were seen as a hindrance. Three key overarching themes that could describe a successful placement were revealed as “Preparation,” “Welcomed and wanted” and “Supervision experiences”. A conceptual model of clinical placement elements conducive to nursing students’ learning was developed to enhance understanding of the complexities associated with supervision. The findings and model are presented and discussed. Conclusion The conceptual model presents positive elements that influence students’ clinical placement experiences of learning. This model may provide a framework to guide professional development programs and strategies to support students and supervisors alike, an important step forward in moving beyond the current clinical placement rhetoric.
A randomized phase 2 trial of idiotype vaccination and adoptive autologous T-cell transfer in patients with multiple myeloma
Authors: Qazilbash Muzaffar H. , Saini Neeraj Y. , Cha Soung-chul , Wang Zhe , Stadtmauer Edward A. , Baladandayuthapani Veerabhadran , Lin Heather , Tross Beryl , Honhar Medhavi , Rao Sheetal S. , Kim Kunhwa , Popescu Michael , Szymura Szymon , Zhang Tiantian , Anderson Aaron , Bashir Qaiser , Shpall Elizabeth J. , Orlowski Robert Z. , Levine Bruce L. , Kerr Naseem , Garfall Alfred , Cohen Adam , Vogl Dan T. , Dengel Karen , June Carl H. , Champlin Richard , Kwak Larry W. 
Published: September 2021

AbstractWe hypothesized that combining adoptively transferred autologous T cells with a cancer vaccine strategy would enhance therapeutic efficacy by adding antimyeloma idiotype (Id)–keyhole limpet hemocyanin (KLH) vaccine to vaccine-specific costimulated T cells. In this randomized phase 2 trial, patients received either control (KLH only) or Id-KLH vaccine, autologous transplantation, vaccine-specific costimulated T cells expanded ex vivo, and 2 booster doses of assigned vaccine. In 36 patients (KLH, n = 20; Id-KLH, n = 16), no dose-limiting toxicity was seen. At last evaluation, 6 (30%) and 8 patients (50%) had achieved complete remission in KLH-only and Id-KLH arms, respectively (P = .22), and no difference in 3-year progression-free survival was observed (59% and 56%, respectively; P = .32). In a 594 Nanostring nCounter gene panel analyzed for immune reconstitution (IR), compared with patients receiving KLH only, there was a greater change in IR genes in T cells in those receiving Id-KLH relative to baseline. Specifically, upregulation of genes associated with activation, effector function induction, and memory CD8+ T-cell generation after Id-KLH but not after KLH control vaccination was observed. Similarly, in responding patients across both arms, upregulation of genes associated with T-cell activation was seen. At baseline, all patients had greater expression of CD8+ T-cell exhaustion markers. These changes were associated with functional Id-specific immune responses in a subset of patients receiving Id-KLH. In conclusion, in this combination immunotherapy approach, we observed significantly more robust IR in CD4+ and CD8+ T cells in the Id-KLH arm, supporting further investigation of vaccine and adoptive immunotherapy strategies. This trial was registered at www.clinicaltrials.gov as #NCT01426828.
Biological and socioeconomic factors as moderator in relationship between leisure-time physical activity and cardiometabolic risk in adolescents from southern Brazil
Authors: Sehn Ana Paula , Tornquist Debora , Tornquist Luciana , Brazo-Sayavera Javier , Reuter Cézane Priscila 
Published: September 2021

Abstract
Background
Given the important repercussions that sociodemographic factors can have on physical activity, especially in the field of leisure, and cardiometabolic risk, it seems relevant to analyze the implications of these variables on the relationship between physical activity in leisure time (LTPA) and cardiometabolic risk. In this sense, the present study aims to verify the moderating role of biologic and socioeconomic factors in the relationship between LTPA and cardiometabolic risk in adolescents in southern Brazil.

Methods
Cross-sectional study that included 1596 adolescents selected at random (58.2% girls), aged between 10 and 17 years. LTPA, biological and socioeconomic factors were assessed using a self-reported questionnaire and the cardiometabolic risk score (total cholesterol/HDL-c ratio, triglycerides, fasting glucose, systolic blood pressure, and waist circumference, considering the participant’s age and sex) was included as an outcome. Associations and moderations were tested by multiple linear regression models.

Results
It was observed a positive interaction of LTPA and sex (p = 0.048) and LTPA and school system (p = 0.037), and negative interaction of LTPA and skin color (p = 0.040), indicating that these factors were moderators in the relationship between LTPA and clustered cardiometabolic risk score (cMetS) in adolescents. A reduction in cardiometabolic risk was observed according to the increase in weekly minutes of LTPA among boys, non-white adolescents, and students from municipal schools.

Conclusions
The association between LTPA and cardiometabolic risk was moderated by sex, skin color, and school system in adolescents from southern Brazil.
The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
Authors: Mompart Florence , Kamgoué Alain , Lahbib-Mansais Yvette , Robelin David , Bonnet Agnès , Rogel-Gaillard Claire , Kocanova Silvia , Yerle-Bouissou Martine 
Published: September 2021

Abstract
Background
The crucial role of the major histocompatibility complex (MHC) for the immune response to infectious diseases is well-known, but no information is available on the 3D nuclear organization of this gene-dense region in immune cells, whereas nuclear architecture is known to play an essential role on genome function regulation. We analyzed the spatial arrangement of the three MHC regions (class I, III and II) in macrophages using 3D-FISH. Since this complex presents major differences in humans and pigs with, notably, the presence of the centromere between class III and class II regions in pigs, the analysis was implemented in both species to determine the impact of this organization on the 3D conformation of the MHC. The expression level of the three genes selected to represent each MHC region was assessed by quantitative real-time PCR. Resting and lipopolysaccharide (LPS)-activated states were investigated to ascertain whether a response to a pathogen modifies their expression level and their 3D organization.

Results
While the three MHC regions occupy an intermediate radial position in porcine macrophages, the class I region was clearly more peripheral in humans. The BAC center-to-center distances allowed us to propose a 3D nuclear organization of the MHC in each species. LPS/IFNγ activation induces a significant decompaction of the chromatin between class I and class III regions in pigs and between class I and class II regions in humans. We detected a strong overexpression of TNFα (class III region) in both species. Moreover, a single nucleus analysis revealed that the two alleles can have either the same or a different compaction pattern. In addition, macrophage activation leads to an increase in alleles that present a decompacted pattern in humans and pigs.

Conclusions
The data presented demonstrate that: (i) the MHC harbors a different 3D organization in humans and pigs; (ii) LPS/IFNγ activation induces chromatin decompaction, but it is not the same area affected in the two species. These findings were supported by the application of an original computation method based on the geometrical distribution of the three target genes. Finally, the position of the centromere inside the swine MHC could influence chromatin reorganization during the activation process.
The choice of negative control antisense oligonucleotides dramatically impacts downstream analysis depending on the cellular background
Authors: Ducoli Luca , Agrawal Saumya , Hon Chung-Chau , Ramilowski Jordan A. , Sibler Eliane , Tagami Michihira , Itoh Masayoshi , Kondo Naoto , Abugessaisa Imad , Hasegawa Akira , Kasukawa Takeya , Suzuki Harukazu , Carninci Piero , Shin Jay W. , de Hoon Michiel J. L. , Detmar Michael 
Published: September 2021

Abstract
Background
The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism’s physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on robust lineage-specific regulatory programs. The recent technological boost in sequencing approaches unveiled long noncoding RNAs (lncRNAs) as prominent regulatory players of various gene expression levels in a cell-type-specific manner.

Results
To investigate the potential roles of lncRNAs in vascular biology, we performed antisense oligonucleotide (ASO) knockdowns of lncRNA candidates specifically expressed either in human lymphatic or blood vascular endothelial cells (LECs or BECs) followed by Cap Analysis of Gene Expression (CAGE-Seq). Here, we describe the quality control steps adopted in our analysis pipeline before determining the knockdown effects of three ASOs per lncRNA target on the LEC or BEC transcriptomes. In this regard, we especially observed that the choice of negative control ASOs can dramatically impact the conclusions drawn from the analysis depending on the cellular background.

Conclusion
In conclusion, the comparison of negative control ASO effects on the targeted cell type transcriptomes highlights the essential need to select a proper control set of multiple negative control ASO based on the investigated cell types.
Choice of pre-processing pipeline influences clustering quality of scRNA-seq datasets
Authors: Shainer Inbal , Stemmer Manuel 
Published: September 2021

Abstract
Background
Single-cell RNA sequencing (scRNA-seq) has quickly become one of the most dominant techniques in modern transcriptome assessment. In particular, 10X Genomics’ Chromium system, with its high throughput approach, turn key and thorough user guide made this cutting-edge technique accessible to many laboratories using diverse animal models. However, standard pre-processing, including the alignment and cell filtering pipelines might not be ideal for every organism or tissue. Here we applied an alternative strategy, based on the pseudoaligner kallisto, on twenty-two publicly available single cell sequencing datasets from a wide range of tissues of eight organisms and compared the results with the standard 10X Genomics’ Cell Ranger pipeline.

Results
In most of the tested samples, kallisto produced higher sequencing read alignment rates and total gene detection rates in comparison to Cell Ranger. Although datasets processed with Cell Ranger had higher cell counts, outside of human and mouse datasets, these additional cells were routinely of low quality, containing low gene detection rates. Thorough downstream analysis of one kallisto processed dataset, obtained from the zebrafish pineal gland, revealed clearer clustering, allowing the identification of an additional photoreceptor cell type that previously went undetected. The finding of the new cluster suggests that the photoreceptive pineal gland is essentially a bi-chromatic tissue containing both green and red cone-like photoreceptors and implies that the alignment and pre-processing pipeline can affect the discovery of biologically-relevant cell types.

Conclusion
While Cell Ranger favors higher cell numbers, using kallisto results in datasets with higher median gene detection per cell. We could demonstrate that cell type identification was not hampered by the lower cell count, but in fact improved as a result of the high gene detection rate and the more stringent filtering. Depending on the acquired dataset, it can be beneficial to favor high quality cells and accept a lower cell count, leading to an improved classification of cell types.
Genomic variation in captive deer mouse (Peromyscus maniculatus) populations
Authors: Lucius Matthew D. , Ji Hao , Altomare Diego , Doran Robert , Torkian Ben , Havighorst Amanda , Kaza Vimala , Zhang Youwen , Gasparian Alexander V. , Magagnoli Joseph , Shankar Vijay , Shtutman Michael , Kiaris Hippokratis 
Published: September 2021

Abstract
Background
Deer mice (genus Peromyscus) are the most common rodents in North America. Despite the availability of reference genomes for some species, a comprehensive database of polymorphisms, especially in those maintained as living stocks and distributed to academic investigators, is missing. In the present study we surveyed two populations of P. maniculatus that are maintained at the Peromyscus Genetic Stock Center (PGSC) for polymorphisms across their 2.5 × 109 bp genome.

Results
High density of variation was identified, corresponding to one SNP every 55 bp for the high altitude stock (SM2) or 207 bp for the low altitude stock (BW) using snpEff (v4.3). Indels were detected every 1157 bp for BW or 311 bp for SM2. The average Watterson estimator for the BW and SM2 populations is 248813.70388 and 869071.7671 respectively. Some differences in the distribution of missense, nonsense and silent mutations were identified between the stocks, as well as polymorphisms in genes associated with inflammation (NFATC2), hypoxia (HIF1a) and cholesterol metabolism (INSIG1) and may possess value in modeling pathology.

Conclusions
This genomic resource, in combination with the availability of P. maniculatus from the PGSC, is expected to promote genetic and genomic studies with this animal model.
Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease
Authors: Wen Jinhua , Zhao Menghua , Sun Wenxiong , Cheng Xiaohua , Yu Luyi , Cao Duanwen , Li Pu 
Published: September 2021

Abstract
Background
The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABC1B1) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. In the preliminary study, we found that the protein expression of organic anion transporting Polypeptide 1a4 (OATP1B1) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp1a4 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD.

Results
In this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport of Aβ1-42. Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aβ1-42in HEK293T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATPs may act as an important “carrier” for the transport of Aβ1-42 from the blood to the tissues, including liver and brain.

Conclusions
This is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD.
Extensive genomic rearrangements mediated by repetitive sequences in plastomes of Medicago and its relatives
Authors: Wu Shuang , Chen Jinyuan , Li Ying , Liu Ai , Li Ao , Yin Mou , Shrestha Nawal , Liu Jianquan , Ren Guangpeng 
Published: September 2021

Abstract
Background
Although plastomes are highly conserved with respect to gene content and order in most photosynthetic angiosperms, extensive genomic rearrangements have been reported in Fabaceae, particularly within the inverted repeat lacking clade (IRLC) of Papilionoideae. Two hypotheses, i.e., the absence of the IR and the increased repeat content, have been proposed to affect the stability of plastomes. However, this is still unclear for the IRLC species. Here, we aimed to investigate the relationships between repeat content and the degree of genomic rearrangements in plastomes of Medicago and its relatives Trigonella and Melilotus, which are nested firmly within the IRLC.

Results
We detected abundant repetitive elements and extensive genomic rearrangements in the 75 newly assembled plastomes of 20 species, including gene loss, intron loss and gain, pseudogenization, tRNA duplication, inversion, and a second independent IR gain (IR ~ 15 kb in Melilotus dentata) in addition to the previous first reported cases in Medicago minima. We also conducted comparative genomic analysis to evaluate plastome evolution. Our results indicated that the overall repeat content is positively correlated with the degree of genomic rearrangements. Some of the genomic rearrangements were found to be directly linked with repetitive sequences. Tandem repeated sequences have been detected in the three genes with accelerated substitution rates (i.e., accD, clpP, and ycf1) and their length variation could be explained by the insertions of tandem repeats. The repeat contents of the three localized hypermutation regions around these three genes with accelerated substitution rates are also significantly higher than that of the remaining plastome sequences.

Conclusions
Our results suggest that IR reemergence in the IRLC species does not ensure their plastome stability. Instead, repeat-mediated illegitimate recombination is the major mechanism leading to genome instability, a pattern in agreement with recent findings in other angiosperm lineages. The plastome data generated herein provide valuable genomic resources for further investigating the plastome evolution in legumes.
Efficiency of complete omentectomy in patients with resectable gastric cancer: a meta‑analysis and systematic review
Authors: Zhu Akao , Yin Guang , Liu Xinchun , Kong Wencheng , Zhang Yu , Shan Yuqiang , Ying Rongchao , Zhang Jian , Zhou Chunhua 
Published: September 2021

Abstract
Background
We performed a meta-analysis to investigate the efficacy of complete omentectomy (CO) in patients undergoing radical gastrectomy for gastric cancer.

Methods
We conducted a literature search in PubMed, Web of Science, and the Cochrane Library databases for clinical research that compared CO with non-complete omentectomy (NCO). These articles were published prior to April 2021. Overall survival (OS) rates, relapse-free survival (RFS) rates, recurrence rates, operation times, estimates of blood loss, numbers of harvested lymph nodes, complications, and lengths of hospital stays were compared using relative risks (RRs) and weighted mean differences (WMDs). RevMan 5.3 software was used for statistical analysis.

Results
Nine studies that included 3329 patients (1960 in the CO group) and 1369 in the NCO group comprised the analysis. The meta-analysis showed that CO was associated with a decreased 3-year OS rate (RR = 0.94, 95% CI 0.90–0.98, P = 0.005) and 5-year OS rate (RR = 0.93, 95% CI 0.88–0.98, P = 0.007). However, it was not associated with the 3-year RFS rate (RR = 0.97, 95% CI 0.90–1.04, P = 0.44), 5-year RFS (RR = 0.98, 95% CI 0.90–1.06, P = 0.60), or recurrence rate (RR = 1.17, 95% CI 0.95–1.45, P = 0.15) compared to the NCO group. For surgical-related outcomes, significant heterogeneity existed between the studies. Compared to the NCO group, CO was found to be associated with significantly more estimated blood loss (WMD = 250.90, 95% CI 105.90–396.28, P = 0.0007) and less harvested lymph nodes (WMD = − 3.59, 95% CI − 6.88, − 0.29, P = 0.03). Although, there was no significant difference in the surgical time (WMD = 15.93, 95% CI − 0.21, 32.07, P = 0.05). No statistically significant differences were observed in the rates of overall (P = 0.79) and major complications (P = 0.90), or the lengths of hospital stays (P = 0.11) between the two groups.

Conclusions
Based on the available evidence, CO is not superior to NCO in terms of survival. CO is not recommended as a routine surgery for gastric cancer. Future well-designed high-quality RCTs are warranted.