bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full-length transcriptome sequences by a combination of sequencing platforms applied to isoflavonoid and triterpenoid saponin biosynthesis of Astragalus mongholicus Bunge
Authors: Yin Minzhen , Chu Shanshan , Shan Tingyu , Zha Liangping , Peng Huasheng 
Published: June 2021

Abstract
Background
Astragalus mongholicus Bunge is an important medicinal plant used in traditional Chinese medicine. It is rich in isoflavonoids and triterpenoid saponins. Although these active constituents of A. mongholicus have been discovered for a long time, the genetic basis of isoflavonoid and triterpenoid saponin biosynthesis in this plant is virtually unknown because of the lack of a reference genome. Here, we used a combination of next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing to identify genes involved in the biosynthetic pathway of secondary metabolites in A. mongholicus.

Results
In this study, NGS, SMRT sequencing, and targeted compound analysis were combined to investigate the association between isoflavonoid and triterpenoid saponin content, and specific gene expression in the root, stem, and leaves of A. mongholicus. Overall, 643,812 CCS reads were generated, yielding 121,107 non-redundant transcript isoforms with an N50 value of 2124 bp. Based on these highly accurate transcripts, 104,756 (86.50%) transcripts were successfully annotated by any of the seven databases (NR, NT, Swissprot, KEGG, KOG, Pfam and GO). Levels of four isoflavonoids and four astragalosides (triterpenoid saponins) were determined. Forty-four differentially expressed genes (DEGs) involved in isoflavonoid biosynthesis and 44 DEGs from 16 gene families that encode enzymes involved in triterpenoid saponin biosynthesis were identified. Transcription factors (TFs) associated with isoflavonoid and triterpenoid saponin biosynthesis, including 72 MYBs, 53 bHLHs, 64 AP2-EREBPs, and 11 bZIPs, were also identified. The above transcripts showed different expression trends in different plant organs.

Conclusions
This study provides important genetic information on the A. mongholicus genes that are essential for isoflavonoid and triterpenoid saponin biosynthesis, and provides a basis for developing the medicinal value of this plant.
Handoffs and transitions in critical care—understanding scalability: study protocol for a multicenter stepped wedge type 2 hybrid effectiveness-implementation trial
Authors: Lane-Fall Meghan B. , Christakos Athena , Russell Gina C. , Hose Bat-Zion , Dauer Elizabeth D. , Greilich Philip E. , Hong Mershon Bommy , Potestio Christopher P. , Pukenas Erin W. , Kimberly John R. , Stephens-Shields Alisa J. , Trotta Rebecca L. , Beidas Rinad S. , Bass Ellen J. 
Published: June 2021

Abstract
Background
The implementation of evidence-based practices in critical care faces specific challenges, including intense time pressure and patient acuity. These challenges result in evidence-to-practice gaps that diminish the impact of proven-effective interventions for patients requiring intensive care unit support. Research is needed to understand and address implementation determinants in critical care settings.

Methods
The Handoffs and Transitions in Critical Care—Understanding Scalability (HATRICC-US) study is a Type 2 hybrid effectiveness-implementation trial of standardized operating room (OR) to intensive care unit (ICU) handoffs. This mixed methods study will use a stepped wedge design with randomized roll out to test the effectiveness of a customized protocol for structuring communication between clinicians in the OR and the ICU. The study will be conducted in twelve ICUs (10 adult, 2 pediatric) based in five United States academic health systems. Contextual inquiry incorporating implementation science, systems engineering, and human factors engineering approaches will guide both protocol customization and identification of protocol implementation determinants. Implementation mapping will be used to select appropriate implementation strategies for each setting. Human-centered design will be used to create a digital toolkit for dissemination of study findings. The primary implementation outcome will be fidelity to the customized handoff protocol (unit of analysis: handoff). The primary effectiveness outcome will be a composite measure of new-onset organ failure cases (unit of analysis: ICU).

Discussion
The HATRICC-US study will customize, implement, and evaluate standardized procedures for OR to ICU handoffs in a heterogenous group of United States academic medical center intensive care units. Findings from this study have the potential to improve postsurgical communication, decrease adverse clinical outcomes, and inform the implementation of other evidence-based practices in critical care settings.

Trial registration
ClinicalTrials.gov identifier: NCT04571749. Date of registration: October 1, 2020.
Programmed suppression of oxidative phosphorylation and mitochondrial function by gestational alcohol exposure correlate with widespread increases in H3K9me2 that do not suppress transcription
Authors: Chang Richard C. , Thomas Kara N. , Mehta Nicole A. , Veazey Kylee J. , Parnell Scott E. , Golding Michael C. 
Published: June 2021

Abstract
Background
A critical question emerging in the field of developmental toxicology is whether alterations in chromatin structure induced by toxicant exposure control patterns of gene expression or, instead, are structural changes that are part of a nuclear stress response. Previously, we used a mouse model to conduct a three-way comparison between control offspring, alcohol-exposed but phenotypically normal animals, and alcohol-exposed offspring exhibiting craniofacial and central nervous system structural defects. In the cerebral cortex of animals exhibiting alcohol-induced dysgenesis, we identified a dramatic increase in the enrichment of dimethylated histone H3, lysine 9 (H3K9me2) within the regulatory regions of key developmental factors driving histogenesis in the brain. However, whether this change in chromatin structure is causally involved in the development of structural defects remains unknown.

Results
Deep-sequencing analysis of the cortex transcriptome reveals that the emergence of alcohol-induced structural defects correlates with disruptions in the genetic pathways controlling oxidative phosphorylation and mitochondrial function. The majority of the affected pathways are downstream targets of the mammalian target of rapamycin complex 2 (mTORC2), indicating that this stress-responsive complex plays a role in propagating the epigenetic memory of alcohol exposure through gestation. Importantly, transcriptional disruptions of the pathways regulating oxidative homeostasis correlate with the emergence of increased H3K9me2 across genic, repetitive, and non-transcribed regions of the genome. However, although associated with gene silencing, none of the candidate genes displaying increased H3K9me2 become transcriptionally repressed, nor do they exhibit increased markers of canonical heterochromatin. Similar to studies in C. elegans, disruptions in oxidative homeostasis induce the chromatin looping factor SATB2, but in mammals, this protein does not appear to drive increased H3K9me2 or altered patterns of gene expression.

Conclusions
Our studies demonstrate that changes in H3K9me2 associate with alcohol-induced congenital defects, but that this epigenetic change does not correlate with transcriptional suppression. We speculate that the mobilization of SATB2 and increased enrichment of H3K9me2 may be components of a nuclear stress response that preserve chromatin integrity and interactions under prolonged oxidative stress. Further, we postulate that while this response may stabilize chromatin structure, it compromises the nuclear plasticity required for normal differentiation.
SARS-COV-2 infection outcomes in patients with congenital generalized lipodystrophy
Authors: Madeira Mayara Ponte , Freire Erika Bastos Lima , Fernandes Virginia Oliveira , Lima Grayce Ellen da Cruz Paiva , Melo Ivana da Ponte , Montenegro Ana Paula Dias Rangel , Freire José Ednésio da Cruz , Moreira-Nunes Caroline de Fátima Aquino , Montenegro Raquel Carvalho , Colares Jeová Keny Baima , Montenegro Junior Renan Magalhães ,   Brazilian Group for the Study of Inherited and Acquired Lipodystrophies (BRAZLIPO)
Published: June 2021

Abstract
Background
A new strain of human coronavirus (HCoV) spread rapidly around the world. Diabetes and obesity are associated with a worse prognosis in these patients. Congenital Generalized Lipodystrophy (CGL) patients generally have poorly controlled diabetes and require extremely high doses of insulin. There is no documentation in the literature of cases of COVID in CGL patients. Thus, we aimed to evaluate the prevalence of SARS-CoV-2 infection in CGL patients, and the association of their clinical and metabolic characteristics and outcomes.

Methods
This is a cross-sectional study carried out between July and October 2020. Clinical data collected were respiratory or other flu-like symptoms, need of hospitalization in the last three months, CGL comorbidities, and medications in use. Cholesterol, triglycerides, glycohemoglobin A1c levels, anti-SARS-CoV-2 antibodies and nasopharyngeal swab for RT-qPCR were also obtained in all CGL patients. Mann-Whitney U test was used to analyze the characteristics of the participants, verifying the non-adherence of the data to the Gaussian distribution. In investigating the association between categorical variables, we used Pearson's chi-square test and Fisher's exact test. A significance level of 5% was adopted.

Results
Twenty-two CGL patients were assessed. Eight subjects (36.4%) had reactive anti-SARS-CoV-2 antibodies. Only one of these, also presented detectable RT-qPCR. Five individuals (62.5%) were women, median age of 13.5 years (1 to 37). Symptoms like fever, malaise, nausea, diarrhea and chest pain were present, and all asymptomatic patients were children. All subjects had inadequate metabolic control, with no difference between groups. Among positive individuals there was no difference between those with AGPAT2 (75%) and BSCL2 gene mutations (25%) (p > 0.05). No patient needed hospitalization or died.

Conclusions
We described a high prevalence of SARS-CoV-2 infection in CGL patients with a good outcome in all of them. These findings suggest that at least young CGL patients infected by SARS-COV-2 are not at higher risk of poor outcome, despite known severe metabolic comorbidities.
On a class of difference equations with interlacing indices
Authors: Stević Stevo , Ahmed A. El-Sayed , Kosmala Witold , Šmarda Zdeněk 
Published: June 2021

AbstractSome results on the long-term behavior of solutions to a class of difference equations, which includes numerous nonlinear difference equations of various orders that attracted some attention in the last 15 years, are presented. We also present a natural connection among these difference equations, compare some results on the equations with some other ones in the literature, and give a list of a considerable number of difference equations which can be treated in a similar way.
A pilot study of the functionality and clinician acceptance of a clinical decision support tool to improve primary care of opioid use disorder
Authors: Rossom Rebecca C. , Sperl-Hillen JoAnn M. , O’Connor Patrick J. , Crain A. Lauren , Nightingale Laurel , Pylkas Anne , Huntley Kristen V. , Bart Gavin 
Published: June 2021

Abstract
Objective
Most Americans with opioid use disorder (OUD) do not receive indicated medical care. A clinical decision support (CDS) tool for primary care providers (PCPs) could address this treatment gap. Our primary objective was to build OUD-CDS tool and demonstrate its functionality and accuracy. Secondary objectives were to achieve high use and approval rates and improve PCP confidence in diagnosing and treating OUD.

Methods
A convenience sample of 55 PCPs participated. Buprenorphine-waivered PCPs (n = 8) were assigned to the intervention. Non-waivered PCPs (n = 47) were randomized to intervention (n = 24) or control (n = 23). Intervention PCPs received access to the OUD-CDS, which alerted them to patients at potentially increased risk for OUD or overdose and guided diagnosis and treatment. Control PCPs provided care as usual.

Results
The OUD-CDS was functional and accurate following extensive multi-phased testing. PCPs used the OUD-CDS in 5% of encounters with at-risk patients, far less than the goal of 60%. OUD screening confidence increased for all intervention PCPs and OUD diagnosis increased for non-waivered intervention PCPs. Most PCPs (65%) would recommend the OUD-CDS and found it helpful with screening for OUD and discussing and prescribing OUD medications.

Discussion
PCPs generally liked the OUD-CDS, but use rates were low, suggesting the need to modify CDS design, implementation strategies and integration with existing primary care workflows.

Conclusion
The OUD-CDS tool was functional and accurate, but PCP use rates were low. Despite low use, the OUD-CDS improved confidence in OUD screening, diagnosis and use of buprenorphine.
NIH Trial registration NCT03559179. Date of registration: 06/18/2018. URL: https://clinicaltrials.gov/ct2/show/NCT03559179
What do clinicians want? Understanding frontline addiction treatment clinicians’ preferences and priorities to improve the design of measurement-based care technology
Authors: Tauscher Justin S. , Cohn Eliza B. , Johnson Tascha R. , Diteman Kaylie D. , Ries Richard K. , Atkins David C. , Hallgren Kevin A. 
Published: June 2021

Abstract
Background
Measurement-based care (MBC) is the practice of routinely administering standardized measures to support clinical decision-making and monitor treatment progress. Despite evidence of its effectiveness, MBC is rarely adopted in routine substance use disorder (SUD) treatment settings and little is known about the factors that may improve its adoptability in these settings. The current study gathered qualitative data from SUD treatment clinicians about their perceptions of MBC, the clinical outcomes they would most like to monitor in MBC, and suggestions for the design and implementation of MBC systems in their settings.

Methods
Fifteen clinicians from one publicly-funded and two privately-funded outpatient SUD treatment clinics participated in one-on-one research interviews. Interviews focused on clinicians’ perceived benefits, drawbacks, and ideas related to implementing MBC technology into their clinical workflows. Interviews were audio recorded, transcribed, and coded to allow for thematic analysis using a mixed deductive and inductive approach. Clinicians also completed a card sorting task to rate the perceived helpfulness of routinely measuring and monitoring different treatment outcomes.

Results
Clinicians reported several potential benefits of MBC, including improved patient-provider communication, client empowerment, and improved communication between clinicians. Clinicians also expressed potential drawbacks, including concerns about subjectivity in patient self-reports, limits to personalization, increased time burdens, and needing to learn to use new technologies. Clinicians generated several ideas and preferences aimed at minimizing burden of MBC, illustrating clinical changes over time, improving ease of use, and improving personalization. Numerous patient outcomes were identified as “very helpful” to track, including coping skills, social support, and motivation for change.

Conclusions
MBC may be a beneficial tool for improving clinical care in SUD treatment settings. MBC tools may be particularly adoptable if they are compatible with existing workflows, help illustrate gradual and nonlinear progress in SUD treatment, measure outcomes perceived as clinically useful, accommodate multiple use cases and stakeholder groups, and are framed as an additional source of information meant to augment, rather than replace, existing practices and information sources.
A Health Technician-delivered Brief Intervention linked to AUDIT for reduction of alcohol use in Chilean primary care: a randomized controlled trial
Authors: Barticevic Nicolas A. , Poblete Fernando , Zuzulich Soledad M. , Rodriguez Victoria , Quevedo Diego , Sena Brena F. , Bradshaw Laura 
Published: June 2021

Abstract
Background
Because of the shortage of health professionals in Chilean primary care, Health Technicians (HT) are providing Brief Interventions (BI) for risky alcohol consumption. We compared the efficacy of two AUDIT-linked interventions provided by HTs: an informative leaflet and a BI plus leaflet.

Methods
This is a parallel-group randomized controlled trial with 1:1 randomization. Participants were identified through screening with the Alcohol Use Disorders Identification Test (AUDIT) at five primary care centers between March 2016 and July 2017. People older than 18 years at intermediate-risk (AUDIT score 8 to 15, inclusive) were randomized to receive either an HT-delivered BI (n = 174) or an informative leaflet (n = 168). Only data from participants (n = 294) who completed the 6-month assessment were analyzed. The leaflet was delivered without further advice. It contains alcohol consumption limits, a change planner, and strategies to decrease drinking. The BI was a 5-min discussion on the leaflet´s content plus normative feedback, tailored information on alcohol and health, and a change plan. The change in the AUDIT risk category six months after randomization (primary outcome) was compared among groups with a Chi-squared test. Changes in the secondary outcomes, which were scores on the AUDIT and the AUDIT´s consumption items (AUDIT-C), were compared with T-tests. Mixed-effects linear models adjusted for potential confounders. Outcome adjudicators were blinded to group assignment.

Results
At 6-month follow-up, low-risk alcohol consumption was observed in 119 (80%) participants in the BI group, and in 103 (71%) in the leaflet group, with no difference among groups ($$\chi 2$$

χ
2

[1, N = 294] = 2.6, p = 0.1; adjusted odds ratio 0.6; 95% confidence interval [CI] 0.34, 1.05). The mean AUDIT score decreased by 5.76 points in the BI group, and by 5.07 in the leaflet group, which represents a 0.86 AUDIT point reduction attributable to the BI (secondary outcome) (T = 2.03, p = 0.043; adjusted mean difference 0.86 CI 0.06, 1.66).

Conclusions
The AUDIT-linked BI delivered by HTs was not associated with a greater reduction of risky alcohol consumption than an informative leaflet. Delivering a leaflet could be more efficient than a BI when provided by HTs; however, more research on the effectiveness of the leaflet is needed.
Trial registration ClinicalTrials.gov NCT02642757 (December 30, 2015) https://clinicaltrials.gov/ct2/show/NCT02642757.
Effect of perioperative use of parecoxib on chronic post-surgical pain in elderly patients after hepatectomy: a prospective randomized controlled study
Authors: Ge Xiaodong , Pan Yan , Jin Danfeng , Wang Ying , Ge Shengjin 
Published: June 2021

Abstract
Background
Chronic post-surgical pain (CPSP) has a negative impact on the recovery, quality of life, and physical functioning of elderly patients. This study aimed to test the superiority of parecoxib vs. placebo in preventing chronic post-hepatectomy pain in elderly patients under combined general-epidural anesthesia.

Methods
A total of 105 elderly patients undergoing hepatectomy under combined general-epidural anesthesia were randomized into the parecoxib or placebo group. The primary outcome was the proportion of patients with CPSP 3 months postoperatively. The secondary outcomes included the Short-Form McGill Pain Questionnaire score in CPSP-positive responders, acute pain intensity, postoperative analgesic demand, inflammatory markers change, and postoperative complications within 28 days.

Results
The parecoxib group provided a non-significant absolute 9.1% reduction in the rate of CPSP compared to the placebo group (P = 0.34). The average chronic pain visual analog scale in the parecoxib group was lower than that in the placebo group (P = 0.04). Significantly less moderate-to-severe acute pain at rest (P = 0.04) and with coughing (P < 0.001), less patient-controlled epidural analgesia (PCEA) consumption (P = 0.01), and less rescue analgesia (P < 0.001) were observed in the parecoxib group compared to the placebo group. Furthermore, no between-group difference was observed in inflammatory markers (P > 0.05) and postoperative complications (P = 0.65).

Conclusions
Parecoxib reduced the prevalence of CPSP in elderly patients after hepatectomy under combined general-epidural anesthesia from 44.4 to 35.3% with no statistical significance. Moreover, significantly alleviated CPSP intensity and improved acute pain management were observed.

Trial registration
This study was retrospectively registered in the Chinese Clinical Trial Registry (URL: http://www.chictr.org.cn/edit.aspx?pid=56961&htm=4) on August 3, 2020 (ChiCTR-2,000,035,198).
Effectiveness of modified cutting and suture technique for endonasal caudal septoplasty in correcting nasal obstruction and preventing nasal tip projection loss
Authors: Hosokawa Yu , Miyawaki Takeshi , Akutsu Taisuke , Omura Kazuhiro , Tsumiyama Shinya , Iimura Jiro , Otori Nobuyoshi , Kojima Hiromi 
Published: June 2021

Purpose Caudal septoplasty is a difficult procedure. The cutting and suture technique is suitable for caudal septoplasty, but a batten graft is always necessary and bears the risk of nasal tip projection loss. We established a modified cutting and suture technique (MCAST), without using a batten graft, and investigated its effectiveness in correcting nasal obstruction and preventing nasal tip projection loss. Methods We retrospectively reviewed the medical records of 22 patients who underwent caudal septoplasty using MCAST. Subjective assessment by Nasal Obstruction Symptom Evaluation (NOSE) score and objective assessment by computed tomography (CT) were performed before and after the surgery. For evaluating nasal tip projection, we asked patients about their awareness of external nasal deformity. Additionally, the nasal tip projection was measured by CT and compared before and after surgery. Results The median preoperative NOSE score reduced significantly after MCAST ( P < 0.001). On CT, the ratio of the area of the convex side to that of the concave side in the anterior portion of the nasal cavity increased significantly after MCAST ( P < 0.001). All patients were unaware of external nasal deformity. There were no significant differences in the mean preoperative and postoperative nasal tip height and nasolabial angle. The mean supra tip height was significantly greater postoperatively than preoperatively ( P = 0.02). Conclusions The MCAST was useful for correcting nasal obstruction with caudal septal deviation. There was no postoperative loss of nasal tip projection. The MCAST can be suitable for correcting C-shaped caudal deviations without dislocating the caudal septum from the anterior nasal septum.