bluuebunny/crossref_metadata_2025_split huggingface dataset:
Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome
Authors: Zhao Xiaolan , Zhang Xun , Wu Zhao , Mei Jie , Li Lingling , Wang Yujue 
Published: July 2021

Abstract
Objective
Numerous studies have confirmed the correlation of microRNAs (miRNAs) with human disease, yet few have explored the role of miR-135 in preeclampsia (PE). This study intends to discuss miR-135’s function in inflammatory response in PE by modulating proprotein convertase subtilisin/kexin-6 (PCSK6) and NLR pyrin domain containing 3 (NLRP3).

Methods
The venous blood and placental tissues were collected from PE pregnant women and 25 normal ones. The levels of miR-135, PCSK6 and NLRP3 in placenta tissues of patients were detected. Hypoxia/reoxygenation HTR-8/SVneo and HPT-8 models were established to mimic PE in vitro, and cell proliferation, colony formation, apoptosis rate, invasion, migration and inflammation were detected through gain-of and loss-of-function assays.

Results
MiR-135 was down-regulated, and PCSK6 and NLRP3 were up-regulated in PE patients. Up-regulating miR-135 or silencing PCSK6 strengthened colony formation ability, viability, invasion and migration ability, and weakened apoptosis and inflammation of H/R-treated HTR-8/SVneo and HPT-8 cells. Inhibition of NLRP3 negated the effects of silenced PCSK6 in H/R-treated HTR-8/SVneo and HPT-8 cells.

Conclusions
Altogether, we demonstrate that up-regulated miR-135 or reduced PCSK6 attenuates inflammatory response in PE by restricting NLRP3 inflammasome, which provides novel therapy for PE treatment.
Reduction in acute migraine-specific and non-specific medication use in patients treated with erenumab: post-hoc analyses of episodic and chronic migraine clinical trials
Authors: Tepper Stewart J , Ashina Messoud , Reuter Uwe , Hallström Yngve , Broessner Gregor , Bonner Jo H , Picard Hernan , Cheng Sunfa , Chou Denise E , Zhang Feng , Klatt Jan , Mikol Daniel D 
Published: July 2021

AbstractBackgroundIn patients with migraine, overuse of acute medication, including migraine-specific medication (MSM) such as triptans and ergots, can lead to adverse health outcomes, including development of medication overuse headache. Here, we examined the effect of erenumab on reducing acute medication use, in particular MSM, in patients with episodic migraine (EM) and chronic migraine (CM).MethodsThe current post-hoc analyses were based on data from the double-blind treatment phase (DBTP) of two erenumab studies, a pivotal EM (N = 955) and a pivotal CM (N = 667) trial, and their respective extensions. Patients were administered subcutaneous placebo or erenumab (70 or 140 mg) once monthly. Daily acute headache medication use (including MSM and non-MSM) was recorded using an electronic diary during a 4-week pretreatment baseline period until the end of the treatment period. Outcome measures included change in monthly acute headache medication days (HMD) in acute headache medication users at baseline, and changes in monthly MSM days (MSMD) in MSM users at baseline and non-MSMD in non-MSM users at baseline.ResultsIn total, 60 and 78 % of patients (all acute headache medication users) with EM and CM used MSM at baseline, respectively. For acute headache medication users, the change in mean monthly acute HMD over Months 4, 5 and 6 compared with the pre-DBTP was 1.5, 2.5, and 3.0 for placebo, erenumab 70 mg and 140 mg, respectively for the EM study. The respective change in monthly MSMD in MSM users was 0.5, 2.1 and 2.8, and in monthly non-MSMD in non-MSM users was 2.3, 2.6, and 2.7. In the acute headache medication users at baseline, the change in monthly acute HMD at Month 3 compared with pre-DBTP was 3.4, 5.5, and 6.5 for placebo, erenumab 70 mg and 140 mg, respectively for the CM study. The respective change in monthly MSMD in MSM users was 2.1, 4.5, and 5.4, and in monthly non-MSMD in non-MSM users was 5.9, 6.4, and 6.6. Reductions in MSMD versus placebo were sustained in the extension periods of both studies. Erenumab was also associated with a higher proportion of MSM users achieving ≥ 50 %, ≥ 75 and 100 % reduction from baseline in monthly MSMD versus placebo in both EM and CM.ConclusionsIn both EM and CM, treatment with erenumab is associated with a significant and sustained reduction in the use of acute headache medication, in particular MSM.Trial registrationsNCT02456740; NCT02066415; NCT02174861.
Microbiological findings in emergency department patients with sepsis identified by the Sepsis-3 criteria: a single-center prospective population-based cohort study
Authors: Sørensen Signe Trille , Abdullah S. M. Osama Bin , Sørensen Rune Husås , Dessau Ram , Høiby Niels , Nielsen Finn Erland 
Published: July 2021

Abstract
Background
Studies comparing the microbiological profiles among sepsis patients identified with either Sequential Organ Failure Assessment (SOFA) score or systemic inflammatory response syndrome (SIRS) criteria are limited. The aim was to examine if there are differences in the microbiological findings among septic patients identified by Sepsis-3 criteria compared to patients identified by the previous sepsis criteria, SIRS, and without organ failure. A secondary purpose was to examine if we could identify microbiological characteristics with increased risk of 28-day mortality.

Methods
Prospective cohort study of all adult (≥ 18 years) patients admitted with sepsis to the Emergency Department of Slagelse Hospital, Denmark from 1st October 2017 to 31st March 2018. Information regarding microbiological findings was obtained via linkage between a sepsis database and the local microbiological laboratory data system. Data regarding 28-day mortality were obtained from the Danish Civil Registration System. We used logistic regression to estimate the association between specific microbiological characteristics and 28-day mortality.

Results
A total of 1616 patients were included; 466 (28.8%; 95% CI 26.6%-31.1%) met SOFA criteria, 398 (24.6%; 95% CI 22.5–26.8%) met SIRS criteria. A total of 127 patients (14.7%; 95% CI 12.4–17.2%) had at least one positive blood culture. SOFA patients had more often positive blood cultures compared to SIRS (13.9% vs. 9.5%; 95 CI on difference 0.1–8.7%). Likewise, Gram-positive bacteria (8.6% vs. 2.8%; 95 CI on difference 2.8–8.8%), infections of respiratory origin (64.8% vs. 57.3%; 95 CI on difference 1.0–14%), Streptococcus pneumoniae (3.2% vs. 1.0%; 95% CI on difference 0.3–4.1) and polymicrobial infections (2.6% vs. 0.3% 95 CI on difference 0.8–3.8%) were more common among SOFA patients. Polymicrobial infections (OR 3.70; 95% CI 1.02–13.40), Staphylococcus aureus (OR 6.30; 95% CI 1.33–29.80) and a pool of “other” microorganisms (OR 3.88; 95% CI 1.34–9.79) in blood cultures were independently associated with mortality.

Conclusion
Patients identified with sepsis by SOFA score were more often blood culture-positive. Gram-positive pathogens, pulmonary tract infections, Streptococcus pneumoniae, and polymicrobial infections were also more common among SOFA patients. Polymicrobial infection, Staphylococcus aureus, and a group of other organisms were independently associated with an increased risk of death.
Long-range linkage disequilibrium in French beef cattle breeds
Authors: El Hou Abdelmajid , Rocha Dominique , Venot Eric , Blanquet Véronique , Philippe Romain 
Published: July 2021

Abstract
Background
Linkage disequilibrium (LD) is a key parameter to study the history of populations and to identify and fine map quantitative trait loci (QTL) and it has been studied for many years in animal populations. The advent of new genotyping technologies has allowed whole-genome LD studies in most cattle populations. However, to date, long-range LD (LRLD) between distant variants on the genome has not been investigated in detail in cattle. Here, we present the first comprehensive study of LRLD in French beef cattle by analysing data on 672 Charolais (CHA), 462 Limousine (LIM) and 326 Blonde d’Aquitaine (BLA) individuals that were genotyped on the Illumina BovineHD Beadchip. Furthermore, whole-genome LD and haplotype block structure were analysed in these three breeds.

Results
We computed linkage disequilibrium (r2) values for 5.9, 5.6 and 6.0 billion pairs of SNPs on the 29 autosomes of CHA, LIM and BLA, respectively. Mean r2 values drop to less than 0.1 for distances between SNPs greater than 120 kb. However, for the first time, we detected the existence of LRLD in the three main French beef breeds. In total, 598, 266, and 795 LRLD events (r2 ≥ 0.6) were detected in CHA, LIM and BLA, respectively. Each breed had predominantly population-specific LRLD interactions, although shared LRLD events occurred in a number of regions (55 LRLD events were shared between two breeds and nine between the three breeds). Examples of possible functional gene interactions and QTL co-location were observed with some of these LRLD events, which suggests epistatic selection.

Conclusions
We identified long-range linkage disequilibrium for the first time in French beef cattle populations. Epistatic selection may be the main source of the observed LRLD events, but other forces may also be involved. LRLD information should be accounted for in genome-wide association studies.
PDBeCIF: an open-source mmCIF/CIF parsing and processing package
Authors: van Ginkel Glen , Pravda Lukáš , Dana José M. , Varadi Mihaly , Keller Peter , Anyango Stephen , Velankar Sameer 
Published: July 2021

Abstract
Background
Biomacromolecular structural data outgrew the legacy Protein Data Bank (PDB) format which the scientific community relied on for decades, yet the use of its successor PDBx/Macromolecular Crystallographic Information File format (PDBx/mmCIF) is still not widespread. Perhaps one of the reasons is the availability of easy to use tools that only support the legacy format, but also the inherent difficulties of processing mmCIF files correctly, given the number of edge cases that make efficient parsing problematic. Nevertheless, to fully exploit macromolecular structure data and their associated annotations such as multiscale structures from integrative/hybrid methods or large macromolecular complexes determined using traditional methods, it is necessary to fully adopt the new format as soon as possible.

Results
To this end, we developed PDBeCIF, an open-source Python project for manipulating mmCIF and CIF files. It is part of the official list of mmCIF parsers recorded by the wwPDB and is heavily employed in the processes of the Protein Data Bank in Europe. The package is freely available both from the PyPI repository (http://pypi.org/project/pdbecif) and from GitHub (https://github.com/pdbeurope/pdbecif) along with rich documentation and many ready-to-use examples.

Conclusions
PDBeCIF is an efficient and lightweight Python 2.6+/3+ package with no external dependencies. It can be readily integrated with 3rd party libraries as well as adopted for broad scientific analyses.
neoDL: a novel neoantigen intrinsic feature-based deep learning model identifies IDH wild-type glioblastomas with the longest survival
Authors: Sun Ting , He Yufei , Li Wendong , Liu Guang , Li Lin , Wang Lu , Xiao Zixuan , Han Xiaohan , Wen Hao , Liu Yong , Chen Yifan , Wang Haoyu , Li Jing , Fan Yubo , Zhang Wei , Zhang Jing 
Published: July 2021

AbstractBackgroundNeoantigen based personalized immune therapies achieve promising results in melanoma and lung cancer, but few neoantigen based models perform well in IDH wild-type GBM, and the association between neoantigen intrinsic features and prognosis remain unclear in IDH wild-type GBM. We presented a novel neoantigen intrinsic feature-based deep learning model (neoDL) to stratify IDH wild-type GBMs into subgroups with different survivals.ResultsWe first derived intrinsic features for each neoantigen associated with survival, followed by applying neoDL in TCGA data cohort(AUC = 0.988,pvalue < 0.0001). Leave one out cross validation (LOOCV) in TCGA demonstrated that neoDL successfully classified IDH wild-type GBMs into different prognostic subgroups, which was further validated in an independent data cohort from Asian population. Long-term survival IDH wild-type GBMs identified by neoDL were found characterized by 12 protective neoantigen intrinsic features and enriched in development and cell cycle.ConclusionsThe model can be therapeutically exploited to identify IDH wild-type GBM with good prognosis who will most likely benefit from neoantigen based personalized immunetherapy. Furthermore, the prognostic intrinsic features of the neoantigens inferred from this study can be used for identifying neoantigens with high potentials of immunogenicity.
Epileptiform activity in mouse hippocampal slices induced by moderate changes in extracellular Mg2+, Ca2+, and K+
Authors: Liu Haiyu , Zhang Sai , Zhang Liang 
Published: July 2021

Abstract
Background
Rodent brain slices—particularly hippocampal slices—are widely used in experimental investigations of epileptiform activity. Oxygenated artificial cerebrospinal fluid (ACSF) is used to maintain slices in vitro. Physiological or standard ACSF containing 3–3.5 mM K+, 1–2 mM Mg2+, and 1–3 mM Ca2+ generally does not induce population epileptiform activity, which can be induced by ACSF with high K+ (8–10 mM), low Mg2+, or low Ca2+ alone or in combination. While low-Mg2+ ACSF without intentionally added Mg salt but with contaminating Mg2+ (≤ 50–80 µM) from other salts can induce robust epileptiform activity in slices, it is unclear whether such epileptiform activity can be achieved using ACSF with moderately decreased Mg2+. To explore this issue, we examined the effects of moderately modified (m)ACSF with 0.8 mM Mg2+, 1.3 mM Ca2+, and 5.7 mM K+ on induction of epileptiform discharges in mouse hippocampal slices.

Results
Hippocampal slices were prepared from young (21–28 days old), middle-aged (13–14 months old), and aged (24–26 months old) C57/BL6 mice. Conventional thin (0.4 mm) and thick (0.6 mm) slices were obtained using a vibratome and pretreated with mACSF at 35–36 °C for 1 h prior to recordings. During perfusion with mACSF at 35–36 °C, spontaneous or self-sustained epileptiform field potentials following high-frequency stimulation were frequently recorded in slices pretreated with mACSF but not in those without the pretreatment. Seizure-like ictal discharges were more common in thick slices than in thin slices.

Conclusions
Prolonged exposure to mACSF by pretreatment and subsequent perfusion can induce epileptiform field potentials in mouse hippocampal slices.
Genome-wide survey and expression analysis of NIN-like Protein (NLP) genes reveals its potential roles in the response to nitrate signaling in tomato
Authors: Liu Mengyuan , Zhi Xiaona , Wang Yi , Wang Yang 
Published: July 2021

Abstract
Background
Tomato (Solanum lycopersicum) is one of the most important horticultural crops, with a marked preference for nitrate as an inorganic nitrogen source. The molecular mechanisms of nitrate uptake and assimilation are poorly understood in tomato. NIN-like proteins (NLPs) are conserved, plant-specific transcription factors that play crucial roles in nitrate signaling.

Results
In this study, genome-wide analysis identified six NLP members in tomato genome. These members were clustered into three clades in a phylogenetic tree. Comparative genomic analysis showed that SlNLP genes exhibited collinear relationships to NLPs in Arabidopsis, canola, maize and rice, and that the expansion of the SlNLP family mainly resulted from segmental duplications in the tomato genome. Tissue-specific expression analysis showed that one of the close homologs of AtNLP6/7, SlNLP3, was strongly expressed in roots during both the seedling and flowering stages, that SlNLP4 and SlNLP6 exhibited preferential expression in stems and leaves and that SlNLP6 was expressed at high levels in fruits. Furthermore, the nitrate uptake in tomato roots and the expression patterns of SlNLP genes were measured under nitrogen deficiency and nitrate resupply conditions. Four SlNLPs, SlNLP1, SlNLP2, SlNLP4 and SlNLP6, were upregulated after nitrogen starvation. And SlNLP1 and SlNLP5 were induced rapidly and temporally by nitrate.

Conclusions
These results provide significant insights into the potential diverse functions of SlNLPs to regulate nitrate uptake.
Primary care providers’ perceptions and experiences of family-centered care for older adults: a qualitative study of community-based diabetes management in China
Authors: Tu Jiong , Liao Jing 
Published: July 2021

Abstract
Background
Family-centered care, as a contemporary model of health service delivery, involves a mutually beneficial partnership between healthcare providers, patients and their families. Although evidence on the positive effects of family-centered care on older adults and their families is accumulating, less is known about the providers’ beliefs, attitudes and practices related to family-centeredness, especially regarding community-based primary healthcare services for the rapidly-ageing Chinese population.

Methods
This study investigated Chinese primary care providers’ perceptions and experiences of family-centered care for older adults, using community-based diabetes management services as an example. Ten focus-group interviews involving 48 community health professionals were conducted. Major themes were identified using thematic analysis.

Results
The interviews revealed that the providers acknowledged the importance of the family in older patients’ diabetes management, while their current scope of practice with the patients’ families was limited and informal. The barriers to implementing family-centered care were attributed to structural and environmental obstacles associated with the patients’ families and the community healthcare context and culture. To engage patients’ families more effectively, the providers suggested that family-centered values endorsed by their healthcare organizations and reinforced by policies, a trained interdisciplinary team of health professionals and community social workers, and also that the utilization of technology would be beneficial.

Conclusions
Our study extends the evidence of family-centered care for older adults in Chinese community-based healthcare settings, contributing to the design of a tailored healthcare delivery model embodying ageing in place.
Quantitative evaluation of range and metabolic activity of hepatic alveolar echinococcosis lesion microenvironment using PET/CT and multi-site sampling method
Authors: Aini Abudusalamu , Yimingjiang Maiweilidan , Yasen Aimaiti , Ran Bo , Jiang Tiemin , Li Xiaohong , Wang Jian , Abulizi Abuduaini , Li Zhide , Shao Yingmei , Aji Tuerganaili , Wen Hao 
Published: July 2021

Abstract
Background
Alveolar echinococcosis (AE) lesion microenvironment (LME) is crucial site where parasite-host interactions happen and of great significance during surgery and obtaining liver samples for basic research. However, little is known about quantification of LME range and its’ metabolic activity regarding different lesion characteristics.

Methods
A prospective and retrospective analysis of LME from surgical AE patients was performed. Patients (n = 75) received abdominal computed tomography (CT) and position emission tomography/computed tomography using 18F-fluodeoxyglucose (18F-FDG-PET/CT) within 1 week prior to surgery. Semiquantitatively, calcification was clustered with 0%, < 50% and ≥ 50% degrees at lesion periphery; liquefaction was clustered with 0%, < 50%, 50 ~ 75%, ≥75% degrees at lesion center using volumetric ratio. Tumor to background ratio (TBR) of 18F-FDG standard uptake value (SUV, n = 75) was calculated, and range of 18F-FDG uptake area was measured; Multi-site sampling method (MSS, n = 35) was introduced to obtain histological slides to evaluate immune cell infiltrative ranges.

Results
Altogether six major lesion groups have been identified (A: 0% calcified, 0% liquefied; B: ≥50% calcified, 0% liquefied; C: < 50% calcified, < 50% liquefied; D: ≥50% calcified, < 50% liquefied; E: < 50% calcified, 50 ~ 75% liquefied; F: ≥50% calcified, ≥75% liquefied). Statistically, TBR values respectively were 5.1 ± 1.9, 2.7 ± 1.2, 4.2 ± 1.2, 2.7 ± 0.7, 4.6 ± 1.2, 2.9 ± 1.1 in groups A ~ F, and comparisons showed A > B, A > D, A > F, E > B, E > D, E > F, C > B, C > D, C > F (P < 0.05); LME ranges indicated by PET/CT respectively were 14.9 ± 3.9, 10.6 ± 1.5, 12.3 ± 1.1, 7.8 ± 1.6, 11.1 ± 2.3, 7.0 ± 0.4 mm in groups A ~ F, and comparisons showed A > B, A > D, A > F, A > E, C > B, C > D, C > F, E > D, E > F, B > D, B > F (P < 0.05); LME ranges indicated by MSS respectively were 17.9 ± 4.9, 13.0 ± 2.7, 11.9 ± 2.6, 6.0 ± 2.2, 11.0 ± 4.1, 6.0 ± 2.2 mm in groups A ~ F, and comparisons showed A > C, A > D, A > F, B > D, B > F, C > D, C > F (P < 0.05). Generally, less calcifications indicated higher TBR values and wider LME ranges; and, severer liquefactions indicated smaller LME ranges. Additionally, patients with previous medication history had lower TBR values.

Conclusions
PET/CT and MSS method showed distinct TBRs and LME ranges for different calcifications and liquefactions. This study would be able to provide references for both surgical resections of lesions and more accurate sample acquisitions for basic research targeted to immunology.
Intraoperative monitoring of visual evoked potentials in patients undergoing transsphenoidal surgery for pituitary adenoma: a systematic review
Authors: Jashek-Ahmed Farizeh , Cabrilo Ivan , Bal Jarnail , Sanders Brett , Grieve Joan , Dorward Neil L. , Marcus Hani J. 
Published: July 2021

Abstract
Background
Transsphenoidal surgery is the gold standard for pituitary adenoma resection. Although rare, a serious complication of surgery is worsened vision post-operatively.

Objective
To determine whether, in patients undergoing transsphenoidal surgery for pituitary adenoma, intraoperative monitoring of visual evoked potentials (VEP) is a safe, reproducible, and effective technological adjunct in predicting postoperative visual function.

Methods
The PubMed and OVID platforms were searched between January 1993 and December 2020 to identify publications that (1) featured patients undergoing transsphenoidal surgery for pituitary adenoma, (2) used intraoperative optic nerve monitoring with VEP and (3) reported on safety or effectiveness. Reference lists were cross-checked and expert opinion sought to identify further publications.

Results
Eleven studies were included comprising ten case series and one prospective cohort study. All employed techniques to improve reliability. No safety issues were reported. The only comparative study included described a statistically significant improvement in post-operative visual field testing when VEP monitoring was used. The remaining case-series varied in conclusion. In nine studies, surgical manipulation was halted in the event of a VEP amplitude decrease suggesting a widespread consensus that this is a warning sign of injury to the anterior optic apparatus.

Conclusions
Despite limited and low-quality published evidence regarding intra-operative VEP monitoring, our review suggests that it is a safe, reproducible, and increasingly effective technique of predicting postoperative visual deficits. Further studies specific to transsphenoidal surgery are required to determine its utility in protecting visual function in the resection of complex pituitary tumours.