bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tonoplast-localized transporter OsNRAMP2 is involved in iron homeostasis and affects seed germination in rice
Authors: Li Yun , Li Jingjun , Yu Yihong , Dai Xia , Gong Changyi , Gu Dongfang , Xu Ending , Liu Yiheng , Zou Yu , Zhang Peijiang , Chen Xi , Zhang Wei 
Published: April 2021

Abstract
Vacuolar storage of iron (Fe) is important for Fe homeostasis in plants. When sufficient, excess Fe could be stored in vacuoles for remobilization in the case of Fe deficiency. Although the mechanism of Fe remobilization from vacuoles is critical for crop development under low Fe stress, the transporters that mediate vacuolar Fe translocation into the cytosol in rice remains unknown. Here, we showed that under high Fe2+ concentrations, the Δccc1 yeast mutant transformed with the rice natural resistance-associated macrophage protein 2 gene (OsNRAMP2) became more sensitive to Fe toxicity. In rice protoplasts and transgenic plants expressing Pro35S:OsNRAMP2-GFP, OsNRAMP2 was localized to the tonoplast. Vacuolar Fe content in osnramp2 knockdown lines was higher than in the wild type, while the growth of osnramp2 knockdown plants was significantly influenced by Fe deficiency. Furthermore, the germination of osnramp2 knockdown plants was arrested. Conversely, the vacuolar Fe content of Pro35S:OsNRAMP2-GFP lines was significantly lower than in the wild type, and overexpression of OsNRAMP2 increased shoot biomass under Fe deficiency. Taken together, we propose that OsNRAMP2 transports Fe from the vacuole to the cytosol and plays a pivotal role in seed germination.
Pathogenesis of acephalic spermatozoa syndrome caused by SUN5 variant
Authors: Zhang Duo , Huang Wu-Jian , Chen Guo-Yong , Dong Li-Hong , Tang Ying , Zhang Hui , Li Qing-Qin , Mei Xiao-Yan , Wang Zhi-Hong , Lan Feng-Hua 
Published: April 2021

Abstract
Acephalic spermatozoa syndrome (ASS) is a rare teratozoospermia that leads to male infertility. Previous work suggested a genetic origin. Variants of Sad1 and UNC84 domain containing 5 (SUN5) are the main genetic cause of ASS; however, its pathogenesis remains unclear. Here, we performed whole-exome sequencing in 10 unrelated ASS and identified 2 homozygous variants, c.381delA[p.V128Sfs7*] and c.675C&gt;A[p.Y225X], and 1 compound variant, c.88 C &gt; T[p.R30X] and c.381 delA [p.V128Sfs7*], in SUN5 in 4 patients. The c.381delA variant had been identified as pathogenic in previous reports, while c.675C&gt;A and c.88 C &gt; T were two novel variants which could lead to a premature termination codon (PTC) and resulted in loss of SUN5, and may also be pathogenic. SUN5 mRNA and protein were present at very low levels in ASS patients with SUN5 nonsense mutation. Furthermore, the distribution of outer dense fiber protein 1 (ODF1) and Nesprin3 was altered in sperm of ASS patients with SUN5 variants. The co-immunoprecipitation analysis indicated that SUN5 and ODF1, SUN5 and Nesprin3, and ODF1 and Nesprin3 interacted with each other in transfected HEK293T cells. Thus, we propose that SUN5, Nesprin3, and ODF1 may form a ‘triplet’ structure through interactions at neck of sperm. When gene variants resulted in a loss of SUN5, the ‘triplet’ structure disappears and then the head-tail junction becomes fragile, leading to the occurrence of ASS.
Grand scale genome manipulation via chromosome swapping in Escherichia coli programmed by three one megabase chromosomes
Authors: Yoneji Tatsuya , Fujita Hironobu , Mukai Takahito , Su’etsugu Masayuki 
Published: April 2021

Abstract
In bacterial synthetic biology, whole genome transplantation has been achieved only in mycoplasmas that contain a small genome and are competent for foreign genome uptake. In this study, we developed Escherichia coli strains programmed by three 1-megabase (Mb) chromosomes by splitting the 3-Mb chromosome of a genome-reduced strain. The first split-chromosome retains the original replication origin (oriC) and partitioning (par) system. The second one has an oriC and the par locus from the F plasmid, while the third one has the ori and par locus of the Vibrio tubiashii secondary chromosome. The tripartite-genome cells maintained the rod-shaped form and grew only twice as slowly as their parent, allowing their further genetic engineering. A proportion of these 1-Mb chromosomes were purified as covalently closed supercoiled molecules with a conventional alkaline lysis method and anion exchange columns. Furthermore, the second and third chromosomes could be individually electroporated into competent cells. In contrast, the first split-chromosome was not able to coexist with another chromosome carrying the same origin region. However, it was exchangeable via conjugation between tripartite-genome strains by using different selection markers. We believe that this E. coli-based technology has the potential to greatly accelerate synthetic biology and synthetic genomics.
Systematic review and network meta-analysis of the efficacy of existing treatments for patients with recurrent glioblastoma
Authors: Schritz Anna , Aouali Nassera , Fischer Aurélie , Dessenne Coralie , Adams Roisin , Berchem Guy , Huiart Laetitia , Schmitz Susanne 
Published: April 2021

Abstract

Background
Despite advances in the treatment of cancers over the last years, treatment options for patients with recurrent glioblastoma (rGBM) remain limited with poor outcomes. Many regimens have been investigated in clinical trials; however, there is a lack of knowledge on comparative effectiveness. The aim of this systematic review is to provide an overview of existing treatment strategies and to estimate the relative efficacy of these regimens in terms of progression-free survival (PFS) and overall survival (OS).

Methods
We conducted a systematic review to identify randomized controlled trials (RCTs) investigating any treatment regimen in adult patients suffering from rGBM. Connected studies reporting at least one of our primary outcomes were included in a Bayesian network meta-analysis (NMA) estimating relative treatment effects.

Results
Forty RCTs fulfilled our inclusion criteria evaluating the efficacy of 38 drugs as mono- or combination therapy. Median OS ranged from 2.9 to 18.3 months; median PFS ranged from 0.7 to 6 months. We performed an NMA including 24 treatments that were connected within a large evidence network. Our NMA indicated improvement in PFS with most bevacizumab (BV)-based regimens compared to other regimens. We did not find any differences in OS between treatments.

Conclusion
This systematic review provides a comprehensive overview of existing treatment options for rGBM. The NMA provides relative effects for many of these treatment regimens, which have not been directly compared in RCTs. Overall, outcomes for patients with rGBM remain poor across all treatment options, highlighting the need for innovative treatment options.
SARS-CoV-2 Vaccination During Pregnancy: A Complex Decision
Authors: Wang Elizabeth Wenqian , Parchem Jacqueline G , Atmar Robert L , Clark Eva H 
Published: April 2021

Abstract
As the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines passed UK and US regulatory milestones in late 2020 and early 2021, multiple professional societies offered recommendations to assist pregnant and breastfeeding people as they choose whether to undergo vaccination. Despite such guidance, the lack of data describing vaccine safety, immunogenicity, and efficacy in pregnant and breastfeeding people has made this decision challenging for many. However, even considering the paucity of data, the known risks of coronavirus disease 2019 during pregnancy likely outweigh the not yet fully elucidated risks of SARS-CoV-2 vaccines, which have reassuring safety and efficacy profiles among nonpregnant people.
T-follicular helper cells in malaria infection and roles in antibody induction
Authors: Soon Megan S F , Nalubega Mayimuna , Boyle Michelle J 
Published: April 2021

Abstract
Immunity to malaria is mediated by antibodies that block parasite replication to limit parasite burden and prevent disease. Cytophilic antibodies have been consistently shown to be associated with protection, and recent work has improved our understanding of the direct and Fc-mediated mechanisms of protective antibodies. Antibodies also have important roles in vaccine-mediated immunity. Antibody induction is driven by the specialized CD4+ T cells, T-follicular helper (Tfh) cells, which function within the germinal centre to drive B-cell activation and antibody induction. In humans, circulating Tfh cells can be identified in peripheral blood and are differentiated into subsets that appear to have pathogen/vaccination-specific roles in antibody induction. Tfh cell responses are essential for protective immunity from Plasmodium infection in murine models of malaria. Our understanding of the activation of Tfh cells during human malaria infection and the importance of different Tfh cell subsets in antibody development is still emerging. This review will discuss our current knowledge of Tfh cell activation and development in malaria, and the potential avenues and pitfalls of targeting Tfh cells to improve malaria vaccines.
The spatial structure and dynamical state of the open cluster NGC 2112
Authors: Gao Xinhua , Xu ShouKun , Xue Lei 
Published: April 2021

Abstract
This paper investigates the spatial structure and dynamical state of the old open cluster NGC 2112 based on likely cluster members from Gaia Early Data Release 3. Using the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm, we find 1193 likely cluster members down to G ∼ 21 mag within a radius of 1.°5 from the cluster center. These likely cluster members can be divided into 865 core members and 328 border members by DBSCAN. We find that the core members are, on average, significantly brighter and more centrally concentrated than the border members. This suggests the existence of clear mass segregation within the cluster. We find that the outer regions of the cluster exhibit a slightly elongated shape, which may be caused by external tidal perturbations. We estimate a distance of D = 1108 ± 3 pc for the cluster based on bright core members. We find that NGC 2112 has a cluster radius of Rcl ∼ 40′ (∼12.9 pc) and a core radius of $R_{\rm c} \sim {4{^{\prime }_{.}}8} \pm {0{^{\prime }_{.}}2}$ (∼1.5 pc). This indicates that NGC 2112 has a central concentration parameter of C = log (Rcl/Rc) ∼ 0.92, which is significantly larger than previously thought. In addition, we estimate a total mass of Mcl = 858 ± 12 M⊙ and an initial mass of Mini = (2.2 ± 0.5) × 104 M⊙ for the cluster. This implies that NGC 2112 may have lost more than $90\%$ of its initial mass. Based on the obtained distance and kinematical data, we also calculate the Galactic orbit of the cluster.
The relationship between fasting-induced torpor, sleep, and wakefulness in laboratory mice
Authors: Huang Yi-Ge , Flaherty Sarah J , Pothecary Carina A , Foster Russell G , Peirson Stuart N , Vyazovskiy Vladyslav V 
Published: April 2021

Abstract

Study Objectives
Torpor is a regulated and reversible state of metabolic suppression used by many mammalian species to conserve energy. Whereas the relationship between torpor and sleep has been well-studied in seasonal hibernators, less is known about the effects of fasting-induced torpor on states of vigilance and brain activity in laboratory mice.

Methods
Continuous monitoring of electroencephalogram (EEG), electromyogram (EMG), and surface body temperature was undertaken in adult, male C57BL/6 mice over consecutive days of scheduled restricted feeding.

Results
All animals showed bouts of hypothermia that became progressively deeper and longer as fasting progressed. EEG and EMG were markedly affected by hypothermia, although the typical electrophysiological signatures of non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, and wakefulness enabled us to perform vigilance-state classification in all cases. Consistent with previous studies, hypothermic bouts were initiated from a state indistinguishable from NREM sleep, with EEG power decreasing gradually in parallel with decreasing surface body temperature. During deep hypothermia, REM sleep was largely abolished, and we observed shivering-associated intense bursts of muscle activity.

Conclusions
Our study highlights important similarities between EEG signatures of fasting-induced torpor in mice, daily torpor in Djungarian hamsters and hibernation in seasonally hibernating species. Future studies are necessary to clarify the effects on fasting-induced torpor on subsequent sleep.
Curcumin nicotinate suppresses abdominal aortic aneurysm pyroptosis via lncRNA PVT1/miR-26a/KLF4 axis through regulating the PI3K/AKT signaling pathway
Authors: Xiong Jian-Ming , Liu Hui , Chen Jie , Zou Qing-Qing , Wang Yang-Yi-Jing , Bi Guo-Shan 
Published: April 2021

Abstract
Abdominal aortic aneurysm (AAA) is a chronic dilated disease of the aorta that is characterized by chronic inflammation. Curcumin (Cur) is previously showed to attenuate AAA by inhibiting inflammatory response in ApoE −/− mice. Since Cur has the limitations of aqueous solubility and instability. Here, we focus on the role of curcumin nicotinate (CurTn), a Cur derivative is derived from Cur and nicotinate. An in vitro model of AAA was established by treating vascular smooth muscle cells (VSMCs) with II (Ang-II). Gene and protein expressions were examined by quantitative real-time PCR (qPCR) or western blotting. Cell migration and pyroptosis were determined by transwell assay and flow cytometry. The interaction between plasmacytoma variant translocation 1 (PVT1), miR-26a and krüppel-like factor 4 (KLF4) was predicted by online prediction tool and confirmed by luciferase reporter assay. CurTn reduced Ang-II-induced AAA-associated proteins, inflammatory cytokine expressions, and attenuated pyroptosis in VSMCs. PVT1 overexpression suppressed the inhibitory effect of CurTn on AngII-induced pyroptosis and inflammatory in VSMCs by sponging miR-26a. miR-26a directly targeted KLF4 and suppressed its expression, which eventually led to the deactivation of the PI3K/AKT signaling pathway. Besides, the regulatory effect of CurTn on pyroptosis of VSMCs induced by Ang-II was reversed through the PVT1/miR-26a/KLF4 pathway. In short, CurTn suppressed VSMCs pyroptosis and inflammation though mediation PVT1/miR-26a/KLF4 axis by regulating the PI3K/AKT signaling pathway, CurTn might consider as a potential therapeutic target in the treatment of AAA.
Redondoviridae and periodontitis: a case–control study and identification of five novel redondoviruses from periodontal tissues
Authors: Zhang Yu , Wang Chunmei , Feng Xiping , Chen Xi , Zhang Wen 
Published: April 2021

Abstract
Redondoviridae is a family of DNA viruses recently identified in the human oro-respiratory tract. However, the characteristics of this new virus family are not yet fully understood. The aim of the present study was to investigate the relationship between redondoviruses and chronic periodontitis. In addition, the complete circular genome, phylogenetic relationship, and biological characteristics of novel redondoviruses were analyzed. The gingival tissues of healthy individuals (n = 120) and periodontitis patients (n = 120) were analyzed using nested polymerase chain reaction assays. The prevalence of redondovirus infection in the periodontitis group was 71.67%. Logistic regression analysis revealed an association between redondoviruses and chronic periodontitis after controlling the confounding factors (odds ratio = 2.53). Five novel redondoviruses, named ‘human periodontal circular-like virus (HPeCV)’, were identified in patients with periodontitis and detailed genetic analysis of the viruses was performed. The 3,035–3,056 bp genome contained a capsid protein, a replication-associated protein, an open reading frame 3 protein, and a stem-loop structure. Phylogenetic analysis demonstrated that HPeCV-1, HPeCV-10, and HPeCV-25 formed a cluster. Recombination may be common in the genomes of HPeCVs. Potential antigenic epitopes in the capsid protein, which may be involved in the host immune response, were predicted. In conclusion, periodontitis patients had a significantly higher prevalence of redondoviruses than healthy controls. Genetic characterization enhanced the current understanding of the genetic diversity and pathogenicity of redondoviruses as well as their association with periodontitis in humans. The data presented in this article will expand the current understanding of the epidemiology, genetic diversity, and pathogenicity of redondoviruses.
The Value of an Orthoplastic Approach to Management of Lower Extremity Trauma: Systematic Review and Meta-analysis
Authors: Klifto Kevin M. , Azoury Saïd C. , Othman Sammy , Klifto Christopher S. , Levin L. Scott , Kovach Stephen J. 
Published: April 2021

Background:
Management of traumatic lower extremity injuries requires a skill set of orthopedic surgery and plastic surgery to optimize the return of form and function. A systematic review and meta-analysis was performed comparing demographics, injuries, and surgical outcomes of patients sustaining lower extremity traumatic injuries receiving either orthoplastic management or nonorthoplastic management.

Methods:
Preferred Reporting Items for Systematic Reviews and Meta-Analysis, Cochrane, and GRADE certainty evidence guidelines were implemented for the structure and synthesis of the review. PubMed, Embase, Cochrane Library, Web of Science, Scopus, and CINAHL databases were systematically and independently searched. Nine studies published from 2013 through 2019 compared 1663 orthoplastic managed patients to 692 nonorthoplastic managed patients with traumatic lower extremity injuries.

Results:
Orthoplastic management, compared to nonorthoplastic management likely decreases time to bone fixation [standard mean differences: −0.35, 95% confidence interval (CI): −0.46 to −0.25, P < 0.0001; participants = 1777; studies = 3; I2 = 0%; moderate certainty evidence], use of negative pressure wound therapy [risk ratios (RR): 0.03, 95% CI: 0.00–0.24, P = 0.0007; participants = 189; studies = 2; I2 = 0%; moderate certainty evidence] with reliance on healing by secondary intention (RR: 0.02, 95% CI: 0.00–0.10, P < 0.0001; participants = 189; studies = 2; I2 = 0%; moderate certainty evidence), and risk of wound/osteomyelitis infections (RR: 0.37, 95% CI: 0.23–0.61, P < 0.0001; participants = 224; studies = 3; I2 = 0%; moderate certainty evidence). Orthoplastic management likely results in more free flaps compared to nonorthoplastic management (RR: 3.46, 95% CI: 1.28–9.33, P = 0.01; participants = 592; studies = 5; I2 = 75%; moderate certainty evidence).

Conclusion:
Orthoplastic management of traumatic lower extremity injuries provides a synergistic model to optimize and expedite definitive skeletal fixation and free flap-based soft-tissue coverage for return of extremity form and function.
Adverse Events Associated With Therapeutic Endoscopic Retrograde Pancreatography
Authors: Han Samuel , Attwell Augustin R. , Tatman Philip , Edmundowicz Steven A. , Hammad Hazem T. , Wagh Mihir S. , Wani Sachin , Shah Raj J. 
Published: April 2021

Objectives
Data regarding the safety of endoscopic retrograde pancreatography (ERP) are limited compared with biliary endoscopic retrograde cholangiopancreatography. The aim of this study was to determine adverse events (AEs) associated with therapeutic ERP.

Methods
This single-center retrospective study examined consecutive therapeutic ERPs with the primary intention of cannulating the pancreatic duct. Multivariate logistic regression was performed to identify risk factors for AEs.

Results
A total of 3023 ERPs were performed in 1288 patients (mean age, 50.3 years; 57.8% female) from January 2000 to January 2017. Overall AE rate was 18.9% with abdominal pain requiring admission (9.8%) and post-ERP pancreatitis (5.7%) being most common. On multivariate analysis, female sex (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.9–2.9), acute recurrent pancreatitis (aOR, 5.0; 95% CI, 1.7–15.3), chronic pancreatitis (aOR, 1.8; 95% CI, 1.3–2.6), and pancreatic sphincter of Oddi dysfunction (aOR, 2.1; 95% CI, 1.4–3.3) were associated with an increased risk of overall AEs. Pancreatic sphincterotomy (aOR, 1.9; 95% CI, 1.5–2.4) and therapeutic stenting (aOR, 1.6; 95% CI, 1.2–2.2) also increased the risk of AEs.

Conclusions
Nearly 1 in 5 patients who undergo therapeutic ERP will experience an AE; however, the rates of major AEs, including post-ERP pancreatitis, bleeding, and perforation, are low.
Updated Meta-analysis of Minimally Invasive Versus Open Surgery for Pancreatic Neuroendocrine Neoplasms
Authors: Zhang Wei , Zhang Jianwei , Che Xu 
Published: April 2021

Objectives
The aim of this study was to compare the short-term and long-term outcomes of minimally invasive surgery (MIS) with those of open pancreas surgery (OPS) for the treatment of pancreatic neuroendocrine neoplasms (pNENs).

Methods
Studies reporting the effects of MIS and OPS for pNENs, published on PubMed, Embase, and Cochrane Library before May 2020 were reviewed.

Results
Seventeen cohort studies with a total of 1853 patients were eligible for analysis, including 655 patients in the MIS group and 1198 patients in the OPS group. The estimated blood loss, postoperative hospitalization time, overall complications, severe complications, spleen preservation, mortality, and recurrence in the MIS group were lower than those in the OPS group. The R0 rate, 3-year overall survival (OS), and 5-year OS in the MIS group were higher than those in the OPS group. There were no significant differences in operative time, postoperative pancreatic fistula, clinical postoperative pancreatic fistula, postoperative bleeding, reoperation, readmission, and 1-year OS.

Conclusions
Minimally invasive surgery can reach lower recurrence rate, higher long-term survival rate, and better outcomes in terms of estimated blood loss, postoperative hospitalization time, R0 rate, mortality, overall complications, and severe complications for pNENs. More high quality studies need to be conducted for further verification.