bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural grafts containing exosomes derived from Schwann cell-like cells promote peripheral nerve regeneration in rats
Authors: Hu Taotao , Chang Shusen , Qi Fang , Zhang Zhonghui , Chen Jiayin , Jiang Lingli , Wang Dali , Deng Chengliang , Nie Kaiyu , Xu Guangchao , Wei Zairong 
Published: April 2023

Abstract

Background
Schwann cell-like cells (SCLCs), differentiated from mesenchymal stem cells, have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies. However, certain clinical obstacles limit their application. Hence, the primary aim of this study was to investigate the role of exosomes derived from SCLCs (SCLCs-exo) in peripheral nerve regeneration.

Methods
SCLCs were differentiated from human amniotic mesenchymal stem cells (hAMSCs) in vitro and validated by immunofluorescence, real-time quantitative PCR and western blot analysis. Exosomes derived from hAMSCs (hAMSCs-exo) and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis, WB analysis and electron microscopy. A prefabricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model. The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury (PNI) regeneration were determined based on the recovery of neurological function and histomorphometric variation. The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell proliferation and migration assessment.

Results
SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100. Compared to hAMSCs-exo, SCLCs-exo significantly enhanced motor function recovery, attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth, myelin formation and angiogenesis in the rat model. Furthermore, hAMSCs-exo and SCLCs-exo were efficiently absorbed by Schwann cells. However, compared to hAMSCs-exo, SCLCs-exo significantly promoted the proliferation and migration of Schwann cells. SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor, myelin positive regulators (SRY-box transcription factor 10, early growth response protein 2 and organic cation/carnitine transporter 6) and myelin proteins (myelin basic protein and myelin protein zero) in Schwann cells.

Conclusions
These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.
Sluggish investment, crisis and firm heterogeneity
Authors: Arrighetti Alessandro , Landini Fabio 
Published: April 2023

Abstract
The stagnation of investments and its causes have attracted great attention in the recent economic debate. In this paper, we show that during the Great Recession, the flattening of the capital formation rate at the firm level is not due to lower average propensity to invest. Rather, it is the result of growing heterogeneity of choices among firms. While a subset of firms is oriented towards increasing investments, another group substantially divest. The result is a polarization of conducts that tend to cancel each other out, resulting in a flattening of aggregate investment. We argue that this asymmetry in firm’s decisions depends on two main factors. The first one is the diversity of corporate strategies, which firms have developed in the past. The second driver is managerial discretion, that plays an important role in the adoption of specific investment/divestment trajectories when faced with a recession. The results of our empirical analysis provide strong support for our hypotheses: after controlling for contextual and firm-specific structural, financial and demographic variables, corporate strategies and managerial discretion in the allocation of liquid assets explain large part of the heterogeneity in investment decisions during the recession. Policy implications are discussed.
Analytical and Non-Analytical Variation May Lead to Inappropriate Antimicrobial Dosing in Neonates: An In Silico Study
Authors: Nguyen Thi A , Kirubakaran Ranita , Schultz Hayley B , Wong Sherilyn , Reuter Stephanie E , McMullan Brendan , Bolisetty Srinivas , Campbell Craig , Horvath Andrea R , Stocker Sophie L 
Published: April 2023

Abstract

Background
Therapeutic drug monitoring (TDM) of aminoglycosides and vancomycin is used to prevent oto- and nephrotoxicity in neonates. Analytical and nonanalytical factors potentially influence dosing recommendations. This study aimed to determine the impact of analytical variation (imprecision and bias) and nonanalytical factors (accuracy of drug administration time, use of non-trough concentrations, biological variation, and dosing errors) on neonatal antimicrobial dosing recommendations.

Methods
Published population pharmacokinetic models and the Australasian Neonatal Medicines Formulary were used to simulate antimicrobial concentration–time profiles in a virtual neonate population. Laboratory quality assurance data were used to quantify analytical variation in antimicrobial measurement methods used in clinical practice. Guideline-informed dosing recommendations based on drug concentrations were applied to compare the impact of analytical variation and nonanalytical factors on antimicrobial dosing.

Results
Analytical variation caused differences in subsequent guideline-informed dosing recommendations in 9.3−12.1% (amikacin), 16.2−19.0% (tobramycin), 12.2−45.8% (gentamicin), and 9.6−19.5% (vancomycin) of neonates. For vancomycin, inaccuracies in drug administration time (45.6%), use of non-trough concentrations (44.7%), within-subject biological variation (38.2%), and dosing errors (27.5%) were predicted to result in more dosing discrepancies than analytical variation (12.5%). Using current analytical performance specifications, tolerated dosing discrepancies would be up to 14.8% (aminoglycosides) and 23.7% (vancomycin).

Conclusions
Although analytical variation can influence neonatal antimicrobial dosing recommendations, nonanalytical factors are more influential. These result in substantial variation in subsequent dosing of antimicrobials, risking inadvertent under- or overexposure. Harmonization of measurement methods and improved patient management systems may reduce the impact of analytical and nonanalytical factors on neonatal antimicrobial dosing.
Hemostatic protocol and risk-reduction surgery for treating coronary artery disease with aortic stenosis in a patient with combined coagulation factor VIII and XI deficiency: a case report
Authors: Honda Sayaka , Shimahara Yusuke , Chikasawa Yushi , Ogino Hitoshi 
Published: April 2023

Abstract

Background
Cardiac surgery remains a significant challenge in patients with coagulation factor VIII (FVIII) deficiency, especially in those with multiple factor deficiencies.

Case summary
A 79-year-old man with combined FVIII and factor XI (FXI) deficiency was admitted for heart failure treatment. Transthoracic echocardiography revealed aortic stenosis (AS) with decreased left ventricular ejection fraction (LVEF) of 40%, mean aortic pressure gradient of 21 mmHg, and aortic valve area of 0.58 cm2. Coronary angiography revealed significant triple-vessel disease. The patient had multiple comorbidities, including diabetic end-stage renal disease treated with hemodialysis and liver cirrhosis (Child–Pugh score of A). Considering the high surgical risk, a two-stage treatment strategy was developed: the first with off-pump coronary artery bypass grafting (CABG), and the second with transcatheter aortic valve implantation if AS symptoms were significant after CABG. A perioperative hemostatic protocol by the author’s heart team was used to appropriately replenish recombinant FVIII concentrates and fresh frozen plasma. The target preoperative and postoperative FVIII coagulation activity values were set at 80–100% and 60–80%, respectively, whereas the target perioperative FXI coagulation activity value was set at 30–45%. Off-pump CABG without aortic manipulation was completed without bleeding events. Transthoracic echocardiography conducted 20 months postoperatively revealed LVEF of 65% and mean aortic pressure gradient of 31 mmHg. The patient leads a normal life 21 months after surgery.

Discussion
The hemostatic protocol and risk-reduction surgery provided satisfactory surgical results in a patient with significant coronary artery disease and AS, high-surgical-risks, and combined FVIII and FXI deficiency.
Early recurrence of attack after myocardial infarction with non-obstructive coronary arteries: a case report
Authors: Morooka Masaki , Kurihara Osamu , Takano Masamichi , Miyauchi Yasushi 
Published: April 2023

Abstract

Background
Diagnostic strategies depend on non-standardized workup, and the causes of myocardial infarction with non-obstructive coronary arteries remain unclear for some patients. Intracoronary imaging is recommended for detecting the missed causes by coronary angiography. Myocardial infarction with non-obstructive coronary arteries is a heterogeneous entity; a meta-analysis of myocardial infarction with non-obstructive coronary artery studies demonstrated that all-cause mortality rate at 1 year is 4.7%, and its prognosis is not so favourable.

Case summary
A 62-year-old man without remarkable medical history complained of acute chest pain at rest, which resolved at his arrival. Although echocardiography and electrocardiogram exhibited normal findings, the concentration of high-sensitive cardiac troponin T increased up to 0.384 from 0.04 ng/mL. Coronary angiography was performed, and mild stenosis of the proximal right coronary artery was detected. He was discharged without catheter intervention and medications as he reported no symptoms. He returned 8 days later because of inferoposterior ST-segment elevation myocardial infarction with ventricular fibrillation. Emergent coronary angiography showed that the mild stenosis of the proximal right coronary artery had progressed to total occlusion. Optical coherence tomography after thrombectomy revealed rupture of the thin-cap fibroatheroma and protruding thrombus.

Discussion
Patients presenting with myocardial infarction with non-obstructive coronary arteries and plaque disruption and/or thrombus detected by optical coherence tomography do not show normal coronaries on coronary angiography. Aggressive investigation into plaque disruption using intracoronary imaging is recommended even if coronary angiography demonstrates mild stenosis to prevent a fatal attack for suspicious cases of myocardial infarction with non-obstructive coronary arteries.
Strong selection is poorly aligned with genetic variation in Ipomoea hederacea: implications for divergence and constraint
Authors: Henry Georgia A , Stinchcombe John R 
Published: April 2023

Abstract
The multivariate evolution of populations is the result of the interactions between natural selection, drift, and the underlying genetic structure of the traits involved. Covariances among traits bias responses to selection, and the multivariate axis which describes the greatest genetic variation is expected to be aligned with patterns of divergence across populations. An exception to this expectation is when selection acts on trait combinations lacking genetic variance, which limits evolutionary change. Here we used a common garden field experiment of individuals from 57 populations of Ipomoea hederacea to characterize linear and nonlinear selection on 5 quantitative traits in the field. We then formally compare patterns of selection to previous estimates of within population genetic covariance structure (the G-matrix) and population divergence in these traits. We found that selection is poorly aligned with previous estimates of genetic covariance structure and population divergence. In addition, the trait combinations favored by selection were generally lacking genetic variation, possessing approximately 15%–30% as much genetic variation as the most variable combination of traits. Our results suggest that patterns of population divergence are likely the result of the interplay between adaptive responses, correlated responses, and selection favoring traits lacking genetic variation.
The Environmental Audit Screening Evaluation: Establishing Reliability and Validity of an Evidence-Based Design Tool
Authors: Kaup Migette L , Calkins Margaret P , Davey Adam , Wrublowsky Robert 
Published: April 2023

Abstract

Background and Objectives
Current assessment tools for long-term care environments have limited generalizability or ability to be linked to specific quality outcomes. To discriminate between different care models, tools are needed to assess important elements of the environmental design. The goal of this project was to systematically evaluate the reliability and validity of the Environmental Audit Screening Evaluation (EASE) tool to better enable the identification of best models in long-term care design to maintain quality of life for persons with dementia and their caregivers.

Research Design and Methods
Twenty-eight living areas (LAs) were selected from 13 sites similar in organizational/operational commitment to person-centered care but with very different LA designs. LAs were stratified into 3 categories (traditional, hybrid, and household) based primarily on architectural/interior features. Three evaluators rated each LA using the Therapeutic Environment Screening Scale (TESS-NH), Professional Environmental Assessment Protocol (PEAP), Environmental Audit Tool (EAT-HC), and EASE. One of each type of LA was reassessed approximately 1 month after the original assessment.

Results
EASE scores were compared against the scores of 3 existing tools to evaluate its construct validity. The EAT-HC was most closely related to the EASE (r = 0.88). The PEAP and the TESS-NH were less correlated to the EASE (r = 0.82 and 0.71, respectively). Analysis of variance indicated that the EASE distinguished between traditional and home-like settings (0.016), but not hybrid LAs. Interrater and inter-occasion reliability and agreement of the EASE were consistently high.

Discussion and Implications
Neither of the 2 U.S.-based existing environmental assessment tools (PEAP and TESS-NH) discriminated between the 3 models of environments. The EAT-HC was most closely aligned with the EASE and performed similarly in differentiating between the traditional and household models, but the dichotomous scoring of the EAT-HC fails to capture environmental nuances. The EASE tool is comprehensive and accounts for nuanced design differences across settings.
Reply to comment on Malkoti et al. () by Haney and Nakahara
Authors: Datta Arjun 
Published: April 2023

SUMMARY
We acknowledge errors in the surface wave Green's tensor shown by Malkoti et al., as pointed out in the Comment by Haney and Nakahara. Using their expressions for Love and Rayleigh wave Green's tensors valid in the near-field, we recompute multicomponent cross-correlation waveforms required for H/V amplitude ratio calculations. All else being equal, these new waveforms are practically indistinguishable from those of Malkoti et al. Differences due to the use of corrected Green's tensors, appear only when the receivers are placed close to the edges of the modelling domain, that is when the receiver separation is large compared to the domain size. Since Malkoti et al. used a modelling domain much larger than the receiver separation, their H/V calculations, and all associated findings, stand.
Association between minimum inhibitory concentration values and mortality risk in patients with Stenotrophomonas maltophilia infections: a retrospective cohort study of electronic health records from 148 US hospitals
Authors: Sarzynski Sadia H , Lawandi Alexander , Warner Sarah , Demirkale Cumhur Y , Strich Jeffrey R , Dekker John P , Babiker Ahmed , Li Willy , Kadri Sameer S 
Published: April 2023

Abstract

Background
Clinical data informing antimicrobial susceptibility breakpoints for Stenotrophomonas maltophilia infections are lacking. We sought to leverage real-world data to identify MIC values within the currently defined susceptible range that could discriminate mortality risk for patients with S. maltophilia infections and guide future breakpoint revisions.

Methods
Inpatients with S. maltophilia infection who received single-agent targeted therapy with levofloxacin or trimethoprim/sulfamethoxazole were identified in the Cerner HealthFacts electronic health record database. Encounters were restricted to those with MIC values reported to be in the susceptible range for both agents. Curation for exact (non-range) MIC values yielded sequentially granular model populations. Logistic regression was used to calculate adjusted OR (aOR) of mortality or hospice discharge associated with different susceptible-range MICs, controlling for patient- and centre-related factors, and infection site, polymicrobial infection and receipt of empirical therapy.

Results
Seventy-three of 851 levofloxacin-treated patients had levofloxacin MIC of exactly 2 mg/L (current Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoint) and served as the reference category for levofloxacin breakpoint models. In breakpoint model I (n = 501), aOR of mortality associated with infection due to isolates with levofloxacin MIC of ≤1 versus 2 mg/L were similar [aOR = 1.79 (95% CI 0.88–3.62), P = 0.11]. In breakpoint model IIa (n = 358), aOR of mortality associated with MIC ≤0.5 versus 2 mg/L were also similar [aOR 0.1.36 (95% CI 0.65–2.83), P = 0.41]. However, breakpoint model IIb (n = 297) displayed higher aOR of mortality associated with an MIC of 1 versus 2 mg/L [aOR 2.36 (95% CI 1.14–4.88), P = 0.02]. Only 9/645 trimethoprim/sulfamethoxazole-treated patients had trimethoprim/sulfamethoxazole MIC of exactly 2/38 mg/L precluding informative models for this agent.

Conclusions
In this retrospective study of real-world patients with S. maltophilia infection, risk-adjusted survival data do not appear to stratify patients clinically within current susceptible-range MIC breakpoint for levofloxacin (≤2 mg/L) by mortality.
Oroxylin a glucuronide as a novel class of reversible inhibitors of Sortase a, combats MRSA-induced infections
Authors: Jiang Xin , Kong Xiangri , Wang Xingye , Yu Zishu , Guo Xuerui , Jin Mengli , Chen Xiaoyu , Guan Jiyu , Wu Cui , Wei Lin , Zhang Chi , Song Guangqi , Jiang Tao , Wang Li , Zhao Yicheng , Song Wu 
Published: April 2023

Abstract

Aims
The main purpose of this study was to study the therapeutical effect of oroxylin A glucuronide (OAG) on methicillin-resistant Staphylococcus aureus (MRSA).

Methods and results
By substrate peptide reaction-based fluorescence resonance energy transfer (FRET) screening, we identified that OAG was an efficient inhibitor of Sortase A (SrtA) with an IC50 of 45.61 μg mL−1, and achieved efficacy in the treatment of Staphylococcus aureus (S. aureus) infections. We further demonstrated that OAG inhibited the adhesion of the S. aureus to fibrinogen, the surface protein A anchoring and diminished biofilm formation. Results obtained from fluorescence quenching assay elucidated a direct interaction between OAG and SrtA. Employing molecular dynamics simulations, we proved that OAG binds to the binding sites of R197, G192, E105, and V168 in the SrtA. Notably, OAG exhibited a robust therapeutic effect in a MRSA-induced pneumonia model.

Conclusions
We identified that OAG as a novel class of reversible inhibitors of SrtA, combats MRSA-induced Infections.
Change at the Top: The Necessity of Transitional Leadership Provisions in the Laws of Independent State-Based Institutions
Authors: Roberts Lyer Kirsten 
Published: April 2023

Abstract
The leadership of independent state-based bodies is critical to their independence and proper functioning. Where leadership ends, either within or outside of the term of office, legislation must ensure that the institution can continue to function. Transitional leadership provisions provide for the continuation of the powers of office in the event of the absence of the mandate holder. Through a textual analysis of the legislation of National Human Rights Institutions (NHRIs) and ombudspersons from 85 jurisdictions, this article identifies a lack of provision for transitional arrangements in enabling laws. It also discusses the problematic aspects of these legislative arrangements where they are present. It identifies the core requirements to ensure there is no leadership gap for an institution. The findings of the article are relevant for a broad range of state-based institutions including anti-corruption and data protection commissions, equality bodies and police oversight bodies, because all state mandated institutions risk their ability to function being undermined where legislation fails to account for a gap in leadership or does not include sufficient protections, such as immunity, for transitional office holders. This article calls for more robust focus on comprehensive transitional provisions in international standards on NHRIs and ombudspersons, and for the inclusion of such transitional provisions in the enabling laws of all legislatively mandated independent state-based institutions.
The efficacy and safety of trastuzumab deruxtecan (T-DXd) in HER2-expressing solid tumours: a single-arm meta-analysis
Authors: Kou Liqiu , Chen Xiu , Xie Xiaolu , Wen Qinglian , Li Jun , Li Yaling 
Published: April 2023

Abstract

Objective
We performed a meta-analysis to assess the efficacy and safety of T-DXd in the treatment of HER2-expressing solid tumours.

Methods
We systematically searched PubMed, Web of Science, Embase and the Cochrane Library and collected studies published before March 17, 2023, on T-DXd for HER2-expressing tumours for a meta-analysis. We performed a subgroup analysis based on the different cancer types and the doses used.

Results
There were 11 studies including 1349 HER2-expressing patients in this meta-analysis. The pooled ORR was 47.91%, and the pooled DCR was 87.01%. The mPFS and mOS combined were 9.63 and 10.71 months, respectively. The most common adverse reactions in grades 1–2 were decreased appetite (49.3%) and vomiting (43.0%). The netropemia (31.2%) and leukopenia (31.2%) were the most common grade 3 and higher adverse reactions. Subgroup analysis showed that breast cancer had the best ORR and DCR, with 66.96 and 96.52%, respectively.

Conclusions
Overall, the efficacy of T-DXd in treating HER2-expressing solid tumours is encouraging, especially breast and non-small cell lung cancers, and has an acceptable safety profile. However, concerns remain about potentially serious treatment adverse events (e.g. interstitial lung disease/pneumonia). More well-designed, large-scale randomized controlled trials are needed to demonstrate our study.