bluuebunny/crossref_metadata_2025_split huggingface dataset:
Children With Down Syndrome and Obstructive Sleep Apnea: Outcomes After Tonsillectomy
Authors: Abijay Claire A. , Tomkies Anna , Rayasam Swathi , Johnson Romaine F. , Mitchell Ron B. 
Published: July 2021

ObjectiveTo evaluate outcomes of tonsillectomy and predictors for persistent obstructive sleep apnea (OSA) in children with Down syndrome in an ethnically diverse population.Study DesignCase series with chart review.SettingUT Southwestern/Children’s Medical Center Dallas.MethodsPolysomnographic, clinical, and demographic characteristics of children with Down syndrome ages 1 to 18 years were collected, including pre‐ and postoperative polysomnography. Simple and multivariable regression models were used for predictors for persistent OSA. P≤. 05 was considered significant.ResultsEighty‐one children were included with a mean age of 6.6 years, 44 of 81 (54%) males, and 53 of 81 (65%) Hispanic. Preoperatively, 60 of 81 (74%) patients had severe OSA. Posttonsillectomy improvements occurred for apnea‐hypopnea index (27.9 to 14.0, P <. 001), arousal index (25.2 to 18.8, P =. 004), percent time with oxygen saturations <90% (8.8% to 3.4%, P =. 003), and oxygen nadir (81.4% to 85%, P <. 001). Forty‐seven children (58%) had persistent OSA. Fifteen children (18.5%) had increased apnea‐hypopnea index postoperatively: 2 from mild to moderate, 2 from mild to severe, and 2 from moderate to severe obstructive sleep apnea. Persistent OSA predictors were asthma (odds ratio, 4.77; 95% CI, 1.61‐14.09; P =. 005) and increasing age (odds ratio, 1.25; 95% CI, 1.09‐1.43; P =. 001).ConclusionChildren with Down syndrome are at high risk for persistent OSA after tonsillectomy with about 20% worsening after tonsillectomy. Asthma and increasing age are predictors for persistent OSA in children with Down syndrome.
Implementation of a Novel Protocol for Preventing Venous Thromboembolism in Otolaryngology Patients
Authors: Levi Lirit , Spectre Galia , Nesichi Ofir , Leader Avi , Raanani Pia , Reuven Yonatan , Schindel Hilla , Shpitzer Thomas , Reifen Ella , Bachar Gideon , Mizrachi Aviram 
Published: July 2021

ObjectiveVenous thromboembolism (VTE) is a preventable cause of postoperative morbidity and mortality. The Caprini risk assessment model (CRAM) is a validated tool for estimating the risk for postoperative VTE. Previous studies demonstrated a low risk of VTE among otorhinolaryngology–head and neck surgery (ORL‐HNS). Hence, our objective was to modify the CRAM‐based protocol to be applicable for otolaryngology patients and assess protocol efficacy and safety.Study DesignObservational pilot study conducted on ORL‐HNS patients undergoing surgery.SettingUniversity‐affiliated tertiary care center.MethodsWe constructed a modified protocol based on the CRAM and previous reports in the ORL‐HNS literature using a reduced postoperative anticoagulation regimen. Primary end point was symptomatic VTE up to 3 months after surgery. Main secondary outcome was postoperative bleeding.ResultsA total of 508 patients were enrolled. Of them, 48% underwent head and neck surgery, 18% direct laryngoscopy and transoral robotic surgery, 15% endoscopic sinus surgery, and 11% otology surgery. Adherence to the protocol was 79%. Mean follow‐up time was 115 days (range, 30‐448 days). Only 1 patient developed deep vein thrombosis, and none developed pulmonary embolism. Two patients had major bleeding not related to the use of anticoagulation.ConclusionsOur novel CRAM‐based protocol appears to be efficacious and safe for VTE prevention in otolaryngology. A larger‐scale study is required to validate these findings.Level of EvidenceLevel 2b.
Feasibility of an Innovative Absorbable Ventilation Tube Designed to Provide Intermediate‐Term Middle Ear Ventilation
Authors: Skovlund Sandra , Cofer Shelagh , Weinreich Heather 
Published: July 2021

Myringotomy with ventilation tube placement is a common surgical procedure performed in children and adults to remove fluid buildup behind the tympanic membrane. However, retention of tubes beyond achievement of therapeutic response increases risk for complications and additional intervention. This small feasibility study was conducted to demonstrate proof of concept of a novel bioabsorbable ventilation tube that provides the necessary duration of ventilation with absorption shortly thereafter. Tubes were placed in 15 ears of 14 patients meeting indications for short or intermediate duration of middle ear ventilation. Two independent examiners documented tube patency and tube absorption status at 3, 6, and 12 weeks or until absorption was complete. Results indicate that average ventilation time was 12 weeks (range, 3 weeks to 18 months). There was no observation of blockage. These findings support the feasibility of a novel bioabsorbable ventilation tube.
Real-World Clinical Experience on the Usage of High-Dose Metformin (1500-2500 mg/day) in Type 2 Diabetes Management
Authors: Das Ashok Kumar , Shah Sanjiv , Singh Santosh Kumar , Juneja Archana , Mishra Niroj Kumar , Dasgupta Arundhati , Deka Nilakshi , Abhyankar Mahesh , Revankar Santosh 
Published: July 2021

Background: To evaluate the clinical characteristics, treatment patterns, and clinical effectiveness and safety of high doses of metformin (1500-2500 mg/day) in Indian adults with type 2 diabetes mellitus (T2DM). Materials and methods: A retrospective, multicentric (n = 241), real-world study included patients with T2DM (aged >18 years) receiving high doses of metformin. Details were retrieved from patient’s medical records. Results: Out of 5695 patients, 62.7% were men with median age was 50.0 years. Hypertension (67.5%) and dyslipidemia (48.7%) were the prevalent comorbidities. Doses of 2000 mg (57.4%) and 1500 mg (29.1%) were the most commonly used doses of metformin and median duration of high-dose metformin therapy was 24.0 months. Metformin twice daily was the most frequently used dosage pattern (94.2%). Up-titration of doses was done in 96.8% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.08%; P < .001). The target glycemic control was achieved in 91.2% patients. A total of 83.0% had decreased weight. Adverse events were reported in 156 patients. Physician global evaluation of efficacy and tolerability showed majority of patients on a good to excellent scale (98.2% and 97.7%). Conclusion: Clinical effectiveness and safety of a high-dose metformin was demonstrated through significant improvement in HbA1c levels and weight reduction.
Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study
Authors: Ashina Messoud , Cohen Joshua M. , Galic Maja , Campos Verena Ramirez , Barash Steve , Ning Xiaoping , Kessler Yoel , Janka Lindsay , Diener Hans-Christoph 
Published: July 2021

AbstractBackgroundFremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab.MethodsEpisodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or  ≥75% reduction in monthly migraine days were evaluated.ResultsOf the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: − 4.7 [5.4]; − 5.1 [4.7]; − 5.5 [5.0]), monthly headache days of at least moderate severity (− 4.5 [5.0]; − 4.8 [4.5]; − 5.2 [4.9]), days per month of acute headache medication use (− 4.3 [5.2]; − 4.9 [4.6]; − 4.8 [4.9]), days with photophobia/phonophobia (− 3.1 [5.3]; − 3.4 [5.3]; − 4.0 [5.2]), and days with nausea or vomiting (− 2.3 [4.6]; − 3.1 [4.5]; − 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%).ConclusionFremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes.Trial registrationClinicalTrials.govNCT03308968(FOCUS).
Benchmark of 16S rRNA gene amplicon sequencing using Japanese gut microbiome data from the V1–V2 and V3–V4 primer sets
Authors: Kameoka Shoichiro , Motooka Daisuke , Watanabe Satoshi , Kubo Ryuichi , Jung Nicolas , Midorikawa Yuki , Shinozaki Natsuko O. , Sawai Yu , Takeda Aya K. , Nakamura Shota 
Published: July 2021

Abstract
Background
16S rRNA gene amplicon sequencing (16S analysis) is widely used to analyze microbiota with next-generation sequencing technologies. Here, we compared fecal 16S analysis data from 192 Japanese volunteers using the modified V1–V2 (V12) and the standard V3–V4 primer (V34) sets to optimize the gut microbiota analysis protocol.

Results
QIIME1 and QIIME2 analysis revealed a higher number of unclassified representative sequences in the V34 data than in the V12 data. The comparison of bacterial composition demonstrated that at the phylum level, Actinobacteria and Verrucomicrobia were detected at higher levels with V34 than with V12. Among these phyla, we observed higher relative compositions of Bifidobacterium and Akkermansia with V34. To estimate the actual abundance, we performed quantitative real-time polymerase chain reaction (qPCR) assays for Akkermansia and Bifidobacterium. We found that the abundance of Akkermansia as detected by qPCR was close to that in V12 data, but was markedly lower than that in V34 data. The abundance of Bifidobacterium detected by qPCR was higher than that in V12 and V34 data.

Conclusions
These results indicate that the bacterial composition derived from the V34 region might differ from the actual abundance for specific gut bacteria. We conclude that the use of the modified V12 primer set is more desirable in the 16S analysis of the Japanese gut microbiota.
Investigating the genetic architecture of disease resilience in pigs by genome-wide association studies of complete blood count traits collected from a natural disease challenge model
Authors: Bai Xuechun , Yang Tianfu , Putz Austin M. , Wang Zhiquan , Li Changxi , Fortin Frédéric , Harding John C. S. , Dyck Michael K. ,   PigGen Canada, Dekkers Jack C. M. , Field Catherine J. , Plastow Graham S. 
Published: July 2021

AbstractBackgroundGenetic improvement for disease resilience is anticipated to be a practical method to improve efficiency and profitability of the pig industry, as resilient pigs maintain a relatively undepressed level of performance in the face of infection. However, multiple biological functions are known to be involved in disease resilience and this complexity means that the genetic architecture of disease resilience remains largely unknown. Here, we conducted genome-wide association studies (GWAS) of 465,910 autosomal SNPs for complete blood count (CBC) traits that are important in an animal’s disease response. The aim was to identify the genetic control of disease resilience.ResultsUnivariate and multivariate single-step GWAS were performed on 15 CBC traits measured from the blood samples of 2743 crossbred (Landrace × Yorkshire) barrows drawn at 2-weeks before, and at 2 and 6-weeks after exposure to a polymicrobial infectious challenge. Overall, at a genome-wise false discovery rate of 0.05, five genomic regions located onSus scrofachromosome (SSC) 2, SSC4, SSC9, SSC10, and SSC12, were significantly associated with white blood cell traits in response to the polymicrobial challenge, and nine genomic regions on multiple chromosomes (SSC1, SSC4, SSC5, SSC6, SSC8, SSC9, SSC11, SSC12, SSC17) were significantly associated with red blood cell and platelet traits collected before and after exposure to the challenge. By functional enrichment analyses using Ingenuity Pathway Analysis (IPA) and literature review of previous CBC studies, candidate genes located nearby significant single-nucleotide polymorphisms were found to be involved in immune response, hematopoiesis, red blood cell morphology, and platelet aggregation.ConclusionsThis study helps to improve our understanding of the genetic basis of CBC traits collected before and after exposure to a polymicrobial infectious challenge and provides a step forward to improve disease resilience.
Transcriptome and metabolome analyses of cold and darkness-induced pellicle cysts of Scrippsiella trochoidea
Authors: Guo Xin , Wang Zhaohui , Liu Lei , Li Yang 
Published: July 2021

Abstract
Background
Dinoflagellates are a group of unicellular organisms that are a major component of aquatic eukaryotes and important contributors to marine primary production. Nevertheless, many dinoflagellates are considered harmful algal bloom (HAB) species due to their detrimental environmental and human health impacts. Cyst formation is widely perceived as an adaptive strategy of cyst-forming dinoflagellates in response to adverse environmental conditions. Dinoflagellate cysts play critical roles in bloom dynamics. However, our insight into the underlying molecular basis of encystment is still limited. To investigate the molecular processes regulating encystment in dinoflagellates, transcriptome and metabolome investigations were performed on cold and darkness-induced pellicle cysts of Scrippsiella trochoidea.

Results
No significant transcriptional response was observed at 2 h; however, massive transcriptome and metabolome reprogramming occurred at 5 h and in pellicle cysts. The gene-to-metabolite network demonstrated that the initial transformation from vegetative cells into pellicle cysts was highly energy demanding through the activation of catabolism, including glycolysis, β-oxidation, TCA cycle and oxidative phosphorylation, to cope with cold-darkness-induced stress. However, after transformation into pellicle cysts, the metabolism was greatly reduced, and various sugars, polyunsaturated fatty acids and amino acids accumulated to prolong survival. The identification of 56 differentially expressed genes (DEGs) related to signal transduction indicated that S. trochoidea received a cold-darkness signal that activated multiple signal transduction pathways, leading to encystment. The elevated expression of genes encoding enzymes involved in ROS stress suggested that pellicle cysts respond to increased oxidative stress. Several cell cycle-related genes were repressed. Intriguingly, 11 DEGs associated with sexual reproduction suggested that pellicle cysts (or some portion thereof) may be a product of sexual reproduction.

Conclusions
This study provides the first transcriptome and metabolome analyses conducted during the encystment of S. trochoidea, an event that requires complex regulatory mechanisms and impacts on population dynamics. The results reveal comprehensive molecular regulatory processes underlying life cycle regulation in dinoflagellates involving signal transduction, gene expression and metabolite profile, which will improve our ability to understand and monitor dinoflagellate blooms.
Linking genotype to phenotype in multi-omics data of small sample
Authors: Guo Xinpeng , Song Yafei , Liu Shuhui , Gao Meihong , Qi Yang , Shang Xuequn 
Published: July 2021

Abstract
Background
Genome-wide association studies (GWAS) that link genotype to phenotype represent an effective means to associate an individual genetic background with a disease or trait. However, single-omics data only provide limited information on biological mechanisms, and it is necessary to improve the accuracy for predicting the biological association between genotype and phenotype by integrating multi-omics data. Typically, gene expression data are integrated to analyze the effect of single nucleotide polymorphisms (SNPs) on phenotype. Such multi-omics data integration mainly follows two approaches: multi-staged analysis and meta-dimensional analysis, which respectively ignore intra-omics and inter-omics associations. Moreover, both approaches require omics data from a single sample set, and the large feature set of SNPs necessitates a large sample size for model establishment, but it is difficult to obtain multi-omics data from a single, large sample set.

Results
To address this problem, we propose a method of genotype-phenotype association based on multi-omics data from small samples. The workflow of this method includes clustering genes using a protein-protein interaction network and gene expression data, screening gene clusters with group lasso, obtaining SNP clusters corresponding to the selected gene clusters through expression quantitative trait locus data, integrating SNP clusters and corresponding gene clusters and phenotypes into three-layer network blocks, analyzing and predicting based on each block, and obtaining the final prediction by taking the average.

Conclusions
We compare this method to others using two datasets and find that our method shows better results in both cases. Our method can effectively solve the prediction problem in multi-omics data of small sample, and provide valuable resources for further studies on the fusion of more omics data.
Postoperative pain treatment with transmuscular quadratus lumborum block and fascia iliaca compartment block in patients undergoing total hip arthroplasty: a randomized controlled trial
Authors: Xia Qin , Ding Wenping , Lin Chao , Xia Jiayi , Xu Yahui , Jia Mengxing 
Published: July 2021

AbstractBackgroundPatients often suffer moderate or even severe pain after total hip arthroplasty; such pain seriously affects early postoperative recovery. This study aimed to investigate the analgesic efficacy of ultrasound-guided transmuscular quadratus lumborum block combined with fascia iliaca compartment block for elderly patients undergoing total hip arthroplasty.MethodsFifty-four patients scheduled for total hip arthroplasty were included in this randomized controlled study. The patients were randomly assigned to receive only transmuscular quadratus lumborum block (group Q) or transmuscular quadratus lumborum block combined with fascia iliaca compartment block (group QF) with ultrasound guidance. Postoperatively in both groups, paracetamol 1 g was regularly administered at 6 h intervals and patient-controlled intravenous analgesia was administered. The primary outcome was cumulative sufentanil consumption via patient-controlled intravenous analgesia 24 h postoperatively. The secondary outcomes included pain degree, time to the first analgesic requirement, joint range of motion, quality of recovery, and the incidence of postoperative complications.ResultsFifty patients were included, and their data were analyzed. The cumulative sufentanil consumption in group QF was significantly lower during the first 24 h after surgery than that in group Q, and the cumulative sufentanil consumption in group QF was reduced at 6–12 and 12–18 h after surgery. The postoperative pain intensity was lower in group QF than in group Q (linear mixed-effects model, the main effect of treatment:P < 0.001). Compared with group Q, group QF had higher quality of recovery and joint range of movement. The time to the first analgesic requirement was longer in group QF than in group Q (log-rank,P < 0.001). There was no statistically significant difference in complications postoperatively between the two groups.ConclusionsOur study provides a multimodal, opioid-sparing analgesic regimen for elderly patients undergoing total hip arthroplasty. The combination of transmuscular quadratus lumborum block and fascia iliaca compartment block provides a significant advantage for early postoperative functional recovery. Further studies are required to confirm the minimum effective dose.Trial registrationThe study was registered on the 21st December 2020 (retrospectively registered) on the Chinese Clinical Trial Registry:ChiCTR2000038686.
Individualized mobile health interventions for cardiovascular event prevention in patients with coronary heart disease: study protocol for the iCARE randomized controlled trial
Authors: Chen Yuling , Ji Meihua , Wu Ying , Deng Ying , Wu Fangqin , Lu Yating 
Published: July 2021

Abstract
Background
Mobile health-based individualized interventions have shown potential effects in managing cardiovascular risk factors. This study aims to assess whether or not mHealth based individualized interventions delivered by an Individualized Cardiovascular Application system for Risk Elimination (iCARE) could reduce the incidence of major cardiovascular events in individuals with coronary heart disease.

Methods
This study is a large-scale, multi-center, parallel-group, open-label, randomized controlled clinical trial. This study will be conducted from September 2019 to December 2025. A total of 2820 patients with coronary heart disease will be recruited from two clinical sites and equally randomized into three groups: the intervention group and two control groups. All participants will be informed of six-time points (at 1, 3, 6, 12, 24, and 36 months after discharge) for follow-up visits. Over a course of 36 months, patients who are randomized to the intervention arm will receive individualized interventions delivered by a fully functional iCARE that using various visualization methods such as comics, videos, pictures, text to provide individualized interventions in addition to standard care. Patients randomized to control group 1 will receive interventions delivered by a modified iCARE that only presented in text in addition to routine care. Control group 2 will only receive routine care. The primary outcome is the incidence of major cardiovascular events within 3 years of discharge. Main secondary outcomes include changes in health behaviors, medication adherence, and cardiovascular health score.

Discussion
If the iCARE trial indeed demonstrates positive effects on patients with coronary heart disease, it will provide empirical evidence for supporting secondary preventive care in this population. Results will inform the design of future research focused on mHealth-based, theory-driven, intelligent, and individualized interventions for cardiovascular risk management.

Trial registration
Trial registered 24th December 2016 with the Chinese Clinical Trial Registry (ChiCTR-INR-16010242). URL: http://www.chictr.org.cn/showproj.aspx?proj=17398.