bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canine DUXC: implications for DUX4 retrotransposition and preclinical models of FSHD
Authors: Wong Chao-Jen , Whiddon Jennifer L , Langford Ashlee T , Belleville Andrea E , Tapscott Stephen J 
Published: December 2021

Abstract
Mis-expression of DUX4 in skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD). Human DUX4 and mouse Dux are retrogenes derived from retrotransposition of the mRNA from the parental DUXC gene. Primates and rodents have lost the parental DUXC gene, and it is unknown whether DUXC had a similar role in driving an early pluripotent transcriptional program. Dogs and other Laurasiatherians have retained DUXC, providing an opportunity to determine the functional similarity to the retrotransposed DUX4 and Dux. Here, we identify the expression of two isoforms of DUXC mRNA in canine testis tissues: one encoding the canonical double homeodomain protein (DUXC), similar to DUX4/Dux, and a second that includes an in-frame alternative exon that disrupts the conserved amino acid sequence of the first homeodomain (DUXC-ALT). The expression of DUXC in canine cells induces a pluripotent program similar to DUX4 and Dux and induces the expression of a similar set of retrotransposons of the ERV/MaLR and LINE-1 families, as well as pericentromeric satellite repeats; whereas DUXC-ALT did not robustly activate gene expression in these assays. Important for preclinical models of FSHD, human DUX4 and canine DUXC show higher conservation of their homeodomains and corresponding binding motifs compared with the conservation between human DUX4 and mouse Dux, and human DUX4 activates a highly similar transcriptional program in canine cells. Together, these findings show that retrotransposition resulted in the loss of an alternatively spliced isoform and that DUXC containing mammals might be good candidates for certain preclinical models ofFSHD.
‘The Greatest Victory’? Challenges and Opportunities for Mediation in Investor-State Dispute Settlement
Authors: de la Rasilla Ignacio 
Published: December 2021

Abstract
This article identifies the rise of mediation as a reaction to the ‘public legitimacy crisis’ experienced by arbitration in investor-State dispute settlement (ISDS) and, more broadly, as a general symptom of the contemporary backlash against international adjudication. It offers an analysis of the nine main challenges that mediation has traditionally faced in ISDS, together with a notice of how recent developments have been contributing to unlocking its underutilized potential. It illustrates the support of numerous States, and in particular of Asian States led by China for dispute prevention and mediation, and provides a critical analysis of some of the limitations of the mediation-related reform options in the agenda of UNCITRAL’s Working Group III including the development of model clauses, a multilateral international investment law advisory centre and a multilateral investment court. The article also examines the recent UNCITRAL secretariat’s guidelines addressing some of the other obstacles faced by mediation in ISDS, including, but not limited to, governance, legislative and policy impediments and the tension between confidentiality in mediation and transparency as a structural goal. The conclusion recaps the main findings of the article and stresses the minimum common denominator quality of mediation as a means to restore balance in a reformed ISDS ‘ecosystem’.
Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression
Authors: Flores-Burgess Antonio , Millón Carmelo , Gago Belen , García-Durán Laura , Cantero-García Noelia , Puigcerver Araceli , Narváez José Angel , Fuxe Kjell , Santín Luis , Díaz-Cabiale Zaida 
Published: December 2021

Abstract

Background
Selective serotonergic reuptake inhibitors, including fluoxetine (FLX), are the most commonly used for the treatment of major depression. However, they are effective for remission in only 30% of patients. Recently, we observed that Galanin (1-15) [GAL(1-15)] enhanced the antidepressant effects of FLX in naïve animals, suggesting a new augmentation strategy in depression.

Methods
We have analyzed in an animal model of depression, the olfactory bulbectomy (OBX) rats, the effect of GAL(1-15) on FLX-mediated responses in the forced swimming test and the sucrose preference test and the involvement of GAL receptor 2 with its antagonist, M871. We have also studied the corticosterone levels in OBX after the coadministration of GAL(1-15) with FLX. Moreover, we studied whether the effects of GAL(1-15) on FLX actions were mediated via auto- and heteroreceptor 5-HT1A (5-HT1AR), analyzing the binding characteristics, mRNA levels, and functionality of 5-HT1AR in the dorsal hippocampus.

Results
GAL(1-15) enhances the antidepressant-like effects induced by FLX in OBX animals in the forced swimming test and the sucrose preference test. The involvement of the GALR2 was demonstrated with M871. Importantly, the mechanism underlying the GAL(1-15)/FLX interactions in the OBX animals involves the 5-HT1AR in the hippocampus at the plasma membrane (increase of affinity and density of 5HT1AR in the DG) and transcriptional (increase of 5HT1AR mRNA levels in DG and CA1) levels. Besides, the coadministration of GAL(1-15) and FLX also reduced OBX-increased corticosterone levels.

Conclusions
The results open the possibility to use GAL(1-15) in combination with FLX as a novel strategy for the treatment of depression.
To swab or not to swab? Using point-of-care tests to detect Group A Streptococcus infections as part of a Sore Throat Test and Treat service in community pharmacy
Authors: Mantzourani Efi , Cannings-John Rebecca , Evans Andrew , Ahmed Haroon 
Published: December 2021

Abstract

Background
The community pharmacy-led Sore Throat Test and Treat (STTT) service in Wales allowed pharmacists to undertake a structured clinical assessment with FeverPAIN/Centor scores and a point-of-care test (POCT) for Group A Streptococcus (GAS) infection. A new service model was temporarily agreed as a result of COVID-19, without routine use of POCT.

Objectives
To explore the impact of removing the requirement for GAS POCT from a community pharmacy STTT service on antibiotic supply.

Methods
Analysis of STTT consultation data, obtained for two periods: November 2018 (date the service went live) to September 2019 (pre-pandemic); and November 2020 (date the new service model was introduced) to May 2021.

Results
For consultations eligible for POCT, the antibiotic supply rate increased from 27% (922/3369) (95% CI: 26%–29%) with the pre-pandemic service model (FeverPAIN/Centor + POCT) to 63% (93/147) (95% CI: 55%–71%) with the new model (FeverPAIN/Centor only); the percentage of patients who were not issued an antibiotic, despite their high clinical score, decreased from 56% (646/1154) to 9.3% (8/86).

Conclusions
Preliminary data suggest that for every 100 STTT consultations with patients with a Centor score of ≥3 or a FeverPAIN score of ≥2, the use of POCT may spare up to 36 courses of antibiotics, increasing to 47 for patients with higher clinical scores, suggesting that the pre-COVID delivery model (FeverPAIN/Centor + POCT) is the optimal pathway and POCT in addition to clinical scores may result in fewer antibiotic prescriptions for sore throat symptoms. These findings have implications for STTT service delivery during and beyond the COVID-19 pandemic.
Lightweight design with metallic additively manufactured cellular structures
Authors: Nguyen Phong Cong Hong , Kim Youngdoo , Choi Young 
Published: December 2021

Abstract
Lightweight design is essential in modern product development and is prevalent in automotive, aerospace, and biomedical applications. The utilization of cellular structure, aided by advancements in additive manufacturing, is among the most effective methods for achieving lightweight design without sacrificing structural integrity and functionality. In this paper, a stress-based structural optimization method is proposed for the design of lightweight components filled with octet functionally graded cellular structures fabricated using selective laser melting (SLM) with the AlSi10Mg alloy. The proposed method includes two main parts: the homogenization-based characterization of SLM-octet-cellular structures and the utilization of the characterized cellular structures for lightweight structure optimum design. Tensile and compression experiments were utilized to validate the proposed homogenization-based characterization method, showing that the simulation and experimental results were in agreement. In addition, the effectiveness of the proposed design optimization method was validated using the three-point bending beam design problem. The experimental results revealed that components filled with functionally graded cellular structures can withstand 15.25$\%$ more load than those with uniform cellular structures. This investigation presents a complete, validated, and industry-oriented lightweight design method, which is useful for the development of future green products.
Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry
Authors: Hu Cheng , Zhuang Xiaoyu , Zhang Jiaqi , Wang Tao , Du Shengnan , Wang Jinping , Peng Xuelian , Cao Qin , Zhang Mingcai , Jiang Yuanye 
Published: December 2021

Abstract

Objective
Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM.

Methods
Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers.

Results
A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM.

Conclusion
The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients’ metabolomics patterns compared to those of patients with only NAFLD or T2DM.
Torque reversal and orbital profile of X-ray pulsar OAO 1657−415
Authors: Liao Zhenxuan , Liu Jiren , Jenke Peter A , Gou Lijun 
Published: December 2021

ABSTRACT
OAO 1657−415 is an atypical supergiant X-ray binary among wind- and disc-fed systems, showing alternate spin-up/spin-down intervals lasting of the order of tens of days. We study different torque states of OAO 1657−415 based on the spin history monitored by Fermi/Gamma-Ray Burst Monitor, together with fluxes from Swift/Burst Alert Telescope (BAT) and Monitor of All-sky X-ray Image/Gas Slit Camera. Its spin frequency derivatives are well correlated with Swift/BAT fluxes during rapid spin-up episodes, anticorrelated with Swift/BAT fluxes during rapid spin-down episodes, and not correlated in between. The orbital profile of spin-down episodes is reduced by a factor of 2 around orbital phases of 0.2 and 0.8 compared to that of spin-up episodes. The orbital hardness ratio profile of spin-down episodes is also lower than that of spin-up episodes around phases close to the mid-eclipse, implying that there is more material between the neutron star and the observer for spin-down episodes than for spin-up episodes around these phases. These results indicate that the torque state of the neutron star is connected with the material flow on orbital scale and support the retrograde/prograde disc accretion scenario for spin-down/spin-up torque reversal.
The Use of Tobacco Industry Vaping Products in the UK and Product Characteristics: A Cross-Sectional Survey
Authors: Cornish Elliot J , Brose Leonie S , McNeill Ann 
Published: December 2021

Abstract

Background
Tobacco industry (TI) companies have entered the UK e-cigarette (“vaping”) market in recent years. However, their motives and ambitions are unclear. This study explored how popular TI vaping products are and who uses them, and how they differ from independent products.

Methods
Secondary analysis of data from a longitudinal web-based survey of smokers, ex-smokers, and vapers (n = 3883) in the UK in 2019. The main study sample consisted of daily and nondaily vapers, who were current or ex-cigarette smokers, and had stated the brand of their preferred e-cigarette device (n = 1202). Proportions using TI and independent brands were calculated and regression analysis assessed associations with sociodemographic and smoking/vaping characteristics between vapers of TI and independent products. Chi-square tests were used to analyze differences between TI and independent products.

Results
Overall, 53.4% used TI products. A university education (67.6%; adjOR = 1.54; 95% CI, 1.140–2.088), nondaily vaping (68.2%; adjOR = 1.39; CI, 1.029–1.880), and cigarette dependence (moderate, strong and very strong urges to smoke) were associated with using TI vaping brands. TI products used were less likely to be refillable (“open”) than independent brands (60.9% vs. 18.3%, chi-square = 228.98, p &lt; .001), more likely to use nicotine salts (16.7% vs. 8.6%, chi-square = 25.04, p &lt; .001) and tobacco flavors (23.8% vs. 17.9%, chi-square = 12.65, p &lt; .001).

Conclusion
TI vaping products were popular in the UK, associations with product and user characteristics suggest that TI products may be less conducive to smoking cessation, although the findings were not always consistent.

Implications
Consequences of regulations need to be carefully considered to ensure that independent producers are not more negatively impacted than tobacco industry producers, and to avoid reducing utility of products for smoking cessation.
Advances in gene editing without residual transgenes in plants
Authors: He Yubing , Mudgett Michael , Zhao Yunde 
Published: December 2021

Abstract
Transgene residuals in edited plants affect genetic analysis, pose off-target risks, and cause regulatory concerns. Several strategies have been developed to efficiently edit target genes without leaving any transgenes in plants. Some approaches directly address this issue by editing plant genomes with DNA-free reagents. On the other hand, DNA-based techniques require another step for ensuring plants are transgene-free. Fluorescent markers, pigments, and chemical treatments have all been employed as tools to distinguish transgenic plants from transgene-free plants quickly and easily. Moreover, suicide genes have been used to trigger self-elimination of transgenic plants, greatly improving the efficiency of isolating the desired transgene-free plants. Transgenes can also be excised from plant genomes using site-specific recombination, transposition or gene editing nucleases, providing a strategy for editing asexually produced plants. Finally, haploid induction coupled with gene editing may make it feasible to edit plants that are recalcitrant to transformation. Here, we evaluate the strengths and weaknesses of recently developed approaches for obtaining edited plants without transgene residuals.
The relationship between the nail and systemic enthesitis in psoriatic arthritis
Authors: Elliott Ashley , Pendleton Adrian , Wright Gary , Rooney Madeleine 
Published: December 2021

Abstract

Objective
Psoriatic nail disease is more common in PsA than in isolated skin psoriasis (PsO). The nail is closely integrated to the DIP joint entheses. US data have shown that those patients with nail disease in PsO are more likely to have systemic enthesitis. We examined whether there was a relationship between nail disease, DIP enthesitis and systemic enthesitis in established PsA.

Methods
Forty-six PsA participants with nail disease underwent US scanning of the nail unit and the DIP entheses along with peripheral entheseal sites according to the Madrid sonographic enthesitis index (MASEI).

Results
At the finger level, there was a mild to moderate correlation between nail US changes and both clinical nail disease and DIP enthesis changes (DIP US) [Spearman correlation (rS) = 0.30, P &lt; 0.001 and rS = 0.16, P &lt; 0.001, respectively]. At the patient level, there was a moderate correlation between the nail US score and nail psoriasis severity index score and DIP US (rS = 0.33, P = 0.024 and rS = 0.43, P = 0.003, respectively). At the patient level, there was also a positive correlation between a higher nail US score and the active peripheral enthesitis score (MASEI-active) (rS = 0.35, P = 0.018). When power Doppler was part of nail US score, similar results were demonstrated at both the finger and patient levels.

Conclusion
This study has demonstrated the utility of nail US imaging and the close relationship, on scanning, between the DIP entheses and the nail unit. In PsA, we have seen a correlation between active US changes at the nail and peripheral enthesitis, which requires further analysis.

Trial registration
ClinicalTrials.gov, https://clinicaltrials.gov, NCT03955861.
Sea–land transition drove terrestrial amphipod diversification in East Asia, with a description of a new species
Authors: Liu Hongguang , Tong Yan , Zheng Yami , Li Shuqiang , Hou Zhonge 
Published: December 2021

Abstract
Sea–land transition caused by marine incursion and regression is hypothesized to be a major driving force in terrestrial biodiversity, providing opportunities for marine ancestors to colonize terrestrial habitats and driving vicariant speciation in distinct geographical regions. Here, we test this hypothesis in East Asia using amphipods of the Morinoia japonica complex. We constructed a dataset from 269 individuals covering all known ranges of this species complex. Phylogenetic and biogeographic analyses revealed that sea–land transition during the Miocene drove the coastal ancestor to invade terrestrial habitats in East Asia and subsequently split into eight biogeographic lineages in eastern China, Korea, Japan and some Pacific islands. Stepping-stone dispersal resulted in a relatively wide distribution of M. japonica, and long-term geographical isolation led to the diversification of the M. japonica complex. Species delimitation analysis suggests that this complex contains eight species. We describe the geographical group from eastern China as a new species, Morinoia aosen sp. nov., based on genetic and morphological comparisons with other geographical groups. Type specimens are deposited in the Institute of Zoology, Chinese Academy of Sciences (IZCAS) in Beijing, China.
Inhalational or total intravenous anesthetic for cardiac surgery: does the debate even exist?
Authors: Makkad Benu , Heinke Timothy Lee , Kertai Miklos D. 
Published: December 2021

Purpose of review
Perioperative myocardial injury related to cardiac surgery is associated with organ dysfunction and increased mortality. Volatile anesthetics (VA) have been used during cardiac surgery for decades because of their direct and indirect preconditioning and protection against ischemia-reperfusion injury. The current review provides a summary of the latest literature comparing pharmacological preconditioning and the potential benefits of using VA versus total intravenous anesthesia (TIVA) for general anesthesia to improve outcomes after cardiac surgery.

Recent findings
Recent literature reports lower mortality and better outcomes when VA is used alone or in combination with remote ischemic preconditioning compared with groups receiving TIVA. However, inconsistent research findings over the years have led to continued debate regarding the anesthetic technique considered more favorable for cardiac surgery.

Summary
Research findings regarding the use of volatile anesthetic versus TIVA for better outcomes after cardiac surgery are inconsistent. Variability in timing, duration, dosing, and type of VA as well as surgical and patient-related factors may have influenced these results. Therefore, either technique can reasonably be adopted depending on provider and institutional preference and used safely in patients undergoing cardiac surgery.
The Use of Carbon Fiber Implants for Impending or Existing Pathologic Fractures
Authors: Herzog Leah N. , Traven Sophia A. , Walton Zeke J. , Leddy Lee R. 
Published: December 2021

Objectives:
To evaluate the utility and complications of using carbon fiber implants (CFIs) compared with standard titanium alloy (TI) intramedullary implants for stabilization of impending or existing pathologic fractures.

Design:
Retrospective comparison.

Patients/Participants:
Ninety-four patients undergoing intramedullary fixation of 100 impending or existing pathologic fractures between 2014-2019 were identified for inclusion.

Main Outcome Measurements:
The primary outcome was postoperative complications. Other outcomes included implant type, pathology, indication, and adjuvant therapy.

Results:
Fifty-three percent of cases used a CFI, whereas 47% of cases used a TI. There were no differences between groups with regard to anatomic location (P = 0.218), indication for surgery (P = 0.066), histology (P = 0.306), or postoperative adjuvant therapy (P = 0.308). Nineteen percent of cases incurred a postoperative complication in each group (P = 0.530), and no differences were noted with regard to complication type including implant failure (P = 0.442) and wound complications (P = 0.322). There was a cost saving of $400 with TI implants compared with CFI.

Conclusions:
This is a high-risk population for postoperative complications after stabilization of pathologic fractures. Although there were no statistical differences in complications between CFI and TI, implant choice depends on patient characteristics and surgeon preference.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Use of Clindamycin for Necrotizing Soft Tissue Infection Decreases Amputation Rate
Authors: Heath David M. , Boyer Braden J. , Ghali Abdullah N. , Momtaz David A. , Nagel Sarah C , Brady Christina I. 
Published: December 2021

Objective:
To identify the impact of clindamycin use on mortality and amputation rates in patients with necrotizing fasciitis.

Design:
Retrospective review.

Setting:
Level 1 trauma center, single-center study.

Patients/Participants:
All patients from 2008 to 2019 with a diagnosis of necrotizing fasciitis. One hundred ninety patients were included in statistical analysis.

Intervention:
Use of clindamycin in the initial antibiotic regimen in the treatment of necrotizing soft tissue infection.

Main Outcome Measurements:
Amputation and mortality rates.

Results:
Patients who received clindamycin had 2.92 times reduced odds of having an amputation when compared with their counterparts, even when American Society of Anesthesiologist scores, comorbidities, smoking, drug use, alcohol consumption, race, ethnicity, sex, and age were controlled for and regardless of other antibiotics started (P = 0.015). There was no significant difference in mortality rate between those patients who did and did not receive clindamycin as part of their initial antibiotic regimen (8.3% vs. 11.6%, respectively; P = 0.453).

Conclusion:
The use of clindamycin in the initial antibiotic regimen for treatment of NSTI was shown to significantly decrease rates of amputation but not mortality.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.