bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early onset of effect following galcanezumab treatment in patients with previous preventive medication failures
Authors: Schwedt Todd J. , Kuruppu Dulanji K. , Dong Yan , Standley Katherine , Yunes-Medina Laura , Pearlman Eric 
Published: March 2021

Abstract
Background
Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives.

Methods
Patients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed.

Results
Galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo − 0.7; galcanezumab − 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p < 0.01, week 1 mean change from baseline: placebo − 0.2; galcanezumab − 1.1). A significantly smaller percentage of patients had a migraine headache on the first day after galcanezumab treatment compared to placebo (28.4% vs 39.2%) and at each subsequent day during week 1 (all p < 0.05). A greater proportion of galcanezumab-treated patients achieved ≥50%, ≥75%, and 100% response at months 1–3 (all p < 0.05) and at weeks 1–4 of month 1 compared to placebo (all p < 0.01).

Conclusion
Galcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments.

Trial registration
ClinicalTrials.gov, NCT03559257. Registered 18 June 2018.
Quantitative analysis of cadmium in rice roots based on LIBS and chemometrics methods
Authors: Wang Wei , Kong Wenwen , Shen Tingting , Man Zun , Zhu Wenjing , He Yong , Liu Fei 
Published: March 2021

Abstract
Background
Excessive cadmium can damage cell structure, inhibit enzyme activity, and affect metabolic process, thus, leading to decline of rice yield and quality. Root is an important organ of crops, the detection of cadmium in root is essential for limitation of cadmium in rice grains.

Results
In this study, laser-induced breakdown spectroscopy (LIBS) was applied for cadmium quantitative analysis. Pretreatment methods, including median absolute deviation, wavelet transform, area normalization, were used to improve spectral stability. Scanning electron microscope and energy-dispersive X-ray spectrometer (SEM/EDS) was first used to analyze ablation pit surface characteristics and the results showed significant positive correlation with spectral lines of Cd II 214.44, Cd II 226.50 and Cd I 228.80 nm. Univariable models of spectral lines showed that three Cd spectral lines have good prediction for cadmium. Fitting methods including linear, logarithmic, and polynomial were used to propose characteristic input variables, and univariable models based on variable of polynomial fitting of I214.44 nm have achieved the best effect (Rp = 0.9821 and RMSEP = 31.1 mg/kg). Besides, partial least squares regression (PLSR), least squares support vector machine (LS-SVM) and extreme learning machine (ELM) were used for multivariate analysis. Compared with univariate analysis, ELM model based on the full spectrum (Rp = 0.9896 and RMSEP = 26.0 mg/kg) had more advantages for cadmium detection.

Conclusion
Compared with traditional methods (150 min), the quantitative detection method based on LIBS technology (less than 5 min) greatly reduces the detection time of heavy metals. The results showed that LIBS has proved to be a reliable method for quantitative detection of cadmium in rice roots. The research can provide theoretical support for timely detection of heavy metals in crop and food production.
SLR-superscaffolder: a de novo scaffolding tool for synthetic long reads using a top-to-bottom scheme
Authors: Guo Lidong , Xu Mengyang , Wang Wenchao , Gu Shengqiang , Zhao Xia , Chen Fang , Wang Ou , Xu Xun , Seim Inge , Fan Guangyi , Deng Li , Liu Xin 
Published: March 2021

Abstract
Background
Synthetic long reads (SLR) with long-range co-barcoding information are now widely applied in genomics research. Although several tools have been developed for each specific SLR technique, a robust standalone scaffolder with high efficiency is warranted for hybrid genome assembly.

Results
In this work, we developed a standalone scaffolding tool, SLR-superscaffolder, to link together contigs in draft assemblies using co-barcoding and paired-end read information. Our top-to-bottom scheme first builds a global scaffold graph based on Jaccard Similarity to determine the order and orientation of contigs, and then locally improves the scaffolds with the aid of paired-end information. We also exploited a screening algorithm to reduce the negative effect of misassembled contigs in the input assembly. We applied SLR-superscaffolder to a human single tube long fragment read sequencing dataset and increased the scaffold NG50 of its corresponding draft assembly 1349 fold. Moreover, benchmarking on different input contigs showed that this approach overall outperformed existing SLR scaffolders, providing longer contiguity and fewer misassemblies, especially for short contigs assembled by next-generation sequencing data. The open-source code of SLR-superscaffolder is available at https://github.com/BGI-Qingdao/SLR-superscaffolder.

Conclusions
SLR-superscaffolder can dramatically improve the contiguity of a draft assembly by integrating a hybrid assembly strategy.
Extensive structural variation in the Bowman-Birk inhibitor family in common wheat (Triticum aestivum L.)
Authors: Xie Yucong , Ravet Karl , Pearce Stephen 
Published: March 2021

Abstract
Background
Bowman-Birk inhibitors (BBI) are a family of serine-type protease inhibitors that modulate endogenous plant proteolytic activities during different phases of development. They also inhibit exogenous proteases as a component of plant defense mechanisms, and their overexpression can confer resistance to phytophagous herbivores and multiple fungal and bacterial pathogens. Dicot BBIs are multifunctional, with a “double-headed” structure containing two separate inhibitory loops that can bind and inhibit trypsin and chymotrypsin proteases simultaneously. By contrast, monocot BBIs have a non-functional chymotrypsin inhibitory loop, although they have undergone internal duplication events giving rise to proteins with multiple BBI domains.

Results
We used a Hidden Markov Model (HMM) profile-based search to identify 57 BBI genes in the common wheat (Triticum aestivum L.) genome. The BBI genes are unevenly distributed, with large gene clusters in the telomeric regions of homoeologous group 1 and 3 chromosomes that likely arose through a series of tandem gene duplication events. The genomes of wheat progenitors also contain contiguous clusters of BBI genes, suggesting this family underwent expansion before the domestication of common wheat. However, the BBI gene family varied in size among different cultivars, showing this family remains dynamic. Because of these expansions, the BBI gene family is larger in wheat than other monocots such as maize, rice and Brachypodium.
We found BBI proteins in common wheat with intragenic homologous duplications of cysteine-rich functional domains, including one protein with four functional BBI domains. This diversification may expand the spectrum of target substrates. Expression profiling suggests that some wheat BBI proteins may be involved in regulating endogenous proteases during grain development, while others were induced in response to biotic and abiotic stresses, suggesting a role in plant defense.

Conclusions
Genome-wide characterization reveals that the BBI gene family in wheat is subject to a high rate of homologous tandem duplication and deletion events, giving rise to a diverse set of encoded proteins. This information will facilitate the functional characterization of individual wheat BBI genes to determine their role in wheat development and stress responses, and their potential application in breeding.
Transcriptional profiling of identified neurons in leech
Authors: Heath-Heckman Elizabeth , Yoo Shinja , Winchell Christopher , Pellegrino Maurizio , Angstadt James , Lammardo Veronica B. , Bautista Diana , De-Miguel Francisco F. , Weisblat David 
Published: March 2021

AbstractBackgroundWhile leeches in the genusHirudohave long been models for neurobiology, the molecular underpinnings of nervous system structure and function in this group remain largely unknown. To begin to bridge this gap, we performed RNASeq on pools of identified neurons of the central nervous system (CNS): sensory T (touch), P (pressure) and N (nociception) neurons; neurosecretory Retzius cells; and ganglia from which these four cell types had been removed.ResultsBioinformatic analyses identified 3565 putative genes whose expression differed significantly among the samples. These genes clustered into 9 groups which could be associated with one or more of the identified cell types. We verified predicted expression patterns through in situ hybridization on whole CNS ganglia, and found that orthologous genes were for the most part similarly expressed in a divergent leech genus, suggesting evolutionarily conserved roles for these genes. Transcriptional profiling allowed us to identify candidate phenotype-defining genes from expanded gene families. Thus, we identified one of eight hyperpolarization-activated cyclic-nucleotide gated (HCN) channels as a candidate for mediating the prominent sag current in P neurons, and found that one of five inositol triphosphate receptors (IP3Rs), representing a sub-family of IP3Rs absent from vertebrate genomes, is expressed with high specificity in T cells. We also identified one of twopiezogenes, two of ~ 65 deg/enacgenes, and one of at least 16transient receptor potential(trp) genes as prime candidates for involvement in sensory transduction in the three distinct classes of leech mechanosensory neurons.ConclusionsOur study defines distinct transcriptional profiles for four different neuronal types within the leech CNS, in addition to providing a second ganglionic transcriptome for the species. From these data we identified five gene families that may facilitate the sensory capabilities of these neurons, thus laying the basis for future work leveraging the strengths of the leech system to investigate the molecular processes underlying and linking mechanosensation, cell type specification, and behavior.
Expression characteristics of pineal miRNAs at ovine different reproductive stages and the identification of miRNAs targeting the AANAT gene
Authors: Di Ran , Liu Qiu-Yue , Song Shu-Hui , Tian Dong-Mei , He Jian-Ning , Ge Ying , Wang Xiang-Yu , Hu Wen-Ping , Mwacharo Joram-Mwashigadi , Pan Zhang-Yuan , Wang Jian-Dong , Ma Qing , Cao Gui-Ling , Jin Hui-Hui , Liang Xiao-Jun , Chu Ming-Xing 
Published: March 2021

AbstractBackgroundMany recent studies have shown that miRNAs play important roles in the regulation of animal reproduction, including seasonal reproduction. The pineal gland is a crucial hub in the regulation of seasonal reproduction. However, little is known about the expression characteristics of pineal miRNAs in different reproductive seasons (anestrus and breeding season). Therefore, the expression profiles and regulatory roles of ovine pineal miRNAs were investigated during different reproductive stages using Solexa sequencing technology and dual luciferase reporter assays.ResultsA total of 427 miRNAs were identified in the sheep pineal gland. Significant differences in miRNA expression were demonstrated between anestrus and the breeding season in terms of the frequency distributions of miRNA lengths, number of expressed miRNAs, and specifically and highly expressed miRNAs in each reproductive stage. KEGG analysis of the differentially expressed (DE) miRNAs between anestrus and the breeding season indicated that they are significantly enriched in pathways related to protein synthesis, secretion and uptake. Furthermore, transcriptome analysis revealed that many target genes of DE miRNAs in the ribosome pathway showed relatively low expression in the breeding season. On the other hand, analyses combining miRNA-gene expression data with target relationship validation in vitro implied that miR-89 may participate in the negative regulation of aralkylamine N-acetyltransferase (AANAT) mRNA expression by targeting its 3’UTR at a unique binding site.ConclusionsOur results provide new insights into the expression characteristics of sheep pineal miRNAs at different reproductive stages and into the negative regulatory effects of pineal miRNAs onAANATmRNA expression.
Ammonia induced microglia activation was associated with limited effects on connexin 43 and aquaporin 4 expression in an astrocyte-microglia co-culture model
Authors: Ismail Fatme Seval , Faustmann Timo Jendrik , Corvace Franco , Tsvetanova Anamariya , Moinfar Zahra , Faustmann Pedro M. 
Published: March 2021

Abstract
Background
Hepatic encephalopathy (HE) is a neurological complication resulting from acute or chronic liver disease. Hyperammonemia leading to astrocyte swelling and cerebral edema in combination with neuroinflammation including microglia activation, mainly contribute to the pathogenesis of HE. However, little is known about microglia and their inflammatory response, as well as their influence on astrocytic channels and astrocyte swelling under hyperammonemia.

Objective
To investigate the effects of ammonia on the microglial activation and morphology in different set-ups of an in vitro astrocyte-microglia co-culture model. Further, potential effects on glial viability, connexin 43 (Cx43) and aquaporin 4 (AQP4) expression were tested.

Methods
Primary rat glial co-cultures of astrocytes containing 5% (M5, representing "physiological" conditions) or 30% (M30, representing "pathological" conditions) of microglia were incubated with 3 mM, 5 mM, 10 mM and 20 mM ammonium chloride (NH4Cl) for 6 h and 24 h in order to mimic the conditions of HE. An MTT assay was performed to measure the viability, proliferation and cytotoxicity of cells. The microglial phenotypes were analyzed by immunocytochemistry. The expression of Cx43 and AQP4 were quantified by immunoblot analysis.

Results
A significant reduction of glial viability was observed in M30 co-cultures after incubation with 20 mM NH4Cl for 6 h, whereas in M5 co-cultures the viability remained unchanged. Microglial activation was detected by immunocytochemistry after incubation with 3 mM, 5 mM and 10 mM NH4Cl for 6 h and 24 h in M5 as well as in M30 co-cultures. The Cx43 expression was slightly increased in M30 co-cultures after 6 h incubation with 5 mM NH4Cl. Also, the AQP4 expression was slightly increased only in M5 co-cultures treated with 10 mM NH4Cl for 6 h. Under the other conditions, Cx43 and AQP4 expression was not affected by NH4Cl.

Conclusions
The novel aspect of our study was the significant microglial activation and decrease of viability after NH4Cl incubation in different set-ups of an in vitro astrocyte-microglia co-culture model, contributing to better understanding of pathophysiological mechanisms of HE. Hyperammonemia led to limited effects on Cx43 and AQP4 expression, the relevance of these minimal changes should be viewed with caution.
Bilateral posterior Quadratus Lumborum block for pain relief after cesarean delivery: a randomized controlled trial
Authors: Pangthipampai Pawinee , Dejarkom Sukanya , Poolsuppasit Suppachai , Luansritisakul Choopong , Tangchittam Suwida 
Published: March 2021

Abstract
Background
Achieving optimal analgesia with few side effects is the goal of pain management after cesarean delivery. Intrathecal (IT) morphine is the current standard but ultrasound-guided quadratus lumborum block (QLB) may offer superior pain control with fewer side effects. This study compared the pain-free period after cesarean delivery among parturients who received spinal block with IT morphine, with IT morphine and bilateral QLB, or only bilateral QLB.

Methods
Parturients having elective cesarean delivery under spinal block were randomized and allocated into IT morphine 0.2 mg with sham QLB (Group IT), IT morphine 0.2 mg and bilateral QLB with 0.25% bupivacaine 25 ml in each side (Group IT+QLB), or bilateral QLB with 0.25% bupivacaine 25 ml in each side (Group QLB). A PCA pump was connected after completion of the QLB or sham block. The first time to PCA morphine requirement was recorded and compared.

Results
Eighty parturients were included. Analysis of Group QLB was terminated early because at the second interim analysis, median pain-free period was significantly shorter in Group QLB [hours (95%CI): 2.50 (1.04–3.96) in Group IT vs. 7.75 (5.67–9.83) in IT+QLB vs. 1.75 (0.75–2.75) in QLB (p < 0.001)]. The median (min, max) amount of morphine required during 24 h was 5.5 (0–25) in Group IT vs. 5.0 (0–36) in IT+QLB vs. 17.5 (1–40) mg in Group QLB (p < 0.001). In the final analysis the median pain-free period was 2.50 (1.23–3.77) hours (95%CI) in Group IT (n = 27) vs. 8.02 (5.96–10.07) in IT+QLB (n = 28). (p = 0.027).

Conclusion
US-QLB used in conjunction with IT morphine yielded a statistically significant longer median pain-free period compared with standard IT morphine alone. However, QLB alone provided inferior pain control compared with standard IT morphine. When combined with IT morphine, QLB could provide additional analgesic benefit as a part of multimodal analgesic regimen, especially during the early postoperative period.

Trial registration
ClinicalTrials.gov no. NCT03199170 Date registered on June 22, 2017. Prospectively registered.
Beliefs about medication as predictors of medication adherence in a prospective cohort study among persons with multiple sclerosis
Authors: Neter Efrat , Glass-Marmor Lea , Wolkowitz Anat , Lavi Idit , Miller Ariel 
Published: March 2021

Abstract
Background
Though adherence to disease-modifying therapies (DMTs) among persons with multiple sclerosis (PwMS) varies and is often below 80%, only few prospective studies on adherence examined predictors beyond demographic and clinical characteristics.

Objectives
Identify antecedents to adherence and persistence to DMT in a prospective design among PwMS.

Methods
PwMS (n = 186) were prospectively assessed at three time points: baseline, 6 (Time 1) and 12 months later (Time 2). Clinical, demographic information and patient-reported medication beliefs, illness perceptions, medication habits, perceived health and affect were surveyed in-person. Adherence and persistence were assessed by a combination of self-reports and retrospective review of medication claims.

Findings
PwMS were 69.9% (Time 1) and 71% (Time 2) adherent to their DMTs and 64.5.9% were persistent. Beliefs about Medications were consistently predictive at both time points (baseline to Time 1 and Time 1 to Time 2) of medication adherence and persistence whereas other perceptions were predictive in some analyses; clinical and demographic characteristics were mostly not predictive of adherence nor persistence. The prospective association of beliefs about medication with adherence held also in multivariate analyses (OR = 0.88, 95% CI 0.78–0.99, p = 0.029).

Conclusions
Adherence and persistence are predicted by medication beliefs of PwMS. As medication beliefs are modifiable, they should be assessed periodically and targeted as a focus of tailored interventions aimed to improve adherence and consequently health outcomes in PwMS.

Registration
Clinical trials registry #NCT02488343, date: 06/08/2015.
A core outcome set development for a French national prospective study about the effect of mediolateral episiotomy on obstetric anal sphincter injury during operative vaginal delivery (INSTRUMODA)
Authors:   the GROG (Groupe de Recherche en Gynécologie Obstétrique), Gachon Bertrand , Schmitz Thomas , Artzner France , Parant Olivier , De Tayrac Renaud , Ducarme Guillaume , Le Ray Camille , Pizzoferrato Anne Cécile , Garabedian Charles , Riethmuller Didier , Pierre Fabrice , Ragot Stephanie , Fritel Xavier 
Published: March 2021

Abstract
Background
We aimed at developing a core outcome and variables of interest set to investigate the effects of mediolateral episiotomy on Obstetric Anal Sphincter Injury (OASI) during and after operative delivery in nulliparous women in a large-scale one-year observational French study including 15,000 women (INSTRUMODA).

Methods
A list of outcomes and variables of interest was suggested to obstetricians participating in the INSTRUMODA study using online questionnaires divided into 7 categories: the woman’s history and course of pregnancy, course of labor, modalities of operative delivery, episiotomy characteristics, immediate maternal morbidity, one-year maternal morbidity, immediate neonatal morbidity. We used a three-round DELPHI method to reach a consensus. In the first round, outcomes and variables considered as essential by 70% or more of obstetricians were included in the corpus whereas they were excluded when 70% rated them as “not important”. In the second round, non-consensual outcomes and variables were reassessed and excluded or definitively included if considered as “not important” or essential by 50% or more of the obstetricians. During the first round, obstetricians were invited to suggest new outcomes and/or variables that were then assessed in the second and third round. We used the same method to develop a core outcome and variables of interest set in a population of women in the community recruited via an association of patients. At the end of the procedure the core outcome and variables of interest sets were merged to provide the final core outcome set for the INSTRUMODA study.

Results
Fifty-three obstetricians and 16 women filled out questionnaires. After the 3 rounds of Delphi procedure in each population, 74 outcomes and variables were consensually reported by obstetricians and 92 by women in the community. By mixing these two consensual corpora we reported a final consensual list of 114 variables of interest and outcomes for both obstetricians and women.

Conclusion
We established a core outcome and variables of interest set among obstetricians and women in the community to investigate the association between mediolateral episiotomy and OASI during operative delivery.

Trial registration
The INSTRUMODA study was registered on https://clinicaltrials.gov on June 25, 2020 (NCT04446780).