bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical Student Ultrasound-Guided Intravenous Catheter Education
Authors: Kule Amy , Richards Rasheed A. , Vazquez Helen M. , Adams William H. , Reed Trent 
Published: February 2021

Introduction
Simulation-based mastery learning (SBML) improves skill transfer to humans. However, limited data exist to support the practice of performing additional training attempts once mastery has been achieved. We explored whether implementing this concept in an SBML model improves skill transfer in ultrasound-guided peripheral intravenous (USGPIV) catheter placement from simulator to humans.

Methods
Forty-eight first- and second-year medical students underwent SBML for USGPIV placement to mastery standards on a simulator once to achieve minimum passing standard based on a 19-item checklist. Next, they completed either 0, 4, or 8 additional mastery level simulated performances in nonconsecutive order before attempting USGPIV placement on a human. An unplanned post hoc retention phase occurred 6 months later where participants' USGPIV skills were reassessed on a second human volunteer using the same checklist.

Results
In this sample, the success rate among the 3 training cohorts did not improve as the number of additional training sessions increased (exact P = 0.60) and were comparable among the 3 cohorts (exact P = 0.82). The overall checklist performance was also comparable among the 3 cohorts (exact P = 0.57). In an unplanned (small) sample of returning participants, the USGPIV retention rate exceeded 80% for those originally assigned to 4 or 8 sessions, whereas the retention rate fell less than 50% for those originally assigned to control. Among these returning participants, the overall success rate was 58% on the initial assessment and was 68% on retention.

Conclusions
In this sample of novices, we were unable to show that up to 8 additional mastery level performances of USGPIV placement on a simulator following SBML training improve skill transfer for both USGPIV placement success and total checklist performance.
Early Locoregional Breast Surgery and Survival in de novo Metastatic Breast Cancer in the Multicenter National ESME Cohort
Authors: Hotton Judicaël , Lusque Amélie , Leufflen Léa , Campone Mario , Levy Christelle , Honart Jean-Francois , Mailliez Audrey , Debled Marc , Gutowski Marian , Leheurteur Marianne , Goncalves Anthony , Jankowski Clementine , Guillermet Sophie , Bachelot Thomas , Ferrero Jean-Marc , Eymard Jean-Christophe , Petit Thierry , Pouget Nicolas , de La Lande Brigitte , Frenel Jean-Sébastien , Villacroux Olivier , Simon Gaëtane , Pons-Tostivint Elvire , Marchai Frédéric 
Published: February 2021

Objective:
The aim was to evaluate the impact of local surgery performed during the year after MBC diagnosis on patients' outcomes from a large reallife cohort.

Summary Background Data:
Locoregional treatment for patients with MBC at the time of diagnosis remains debated.

Methods:
Women with newly diagnosed, de novo stage IV MBC and who started MBC treatment between January 2008 and December 2014 in one of the 18 French Comprehensive Cancer Centers were included (NCT03275311). The impact of local surgery performed during the first year on overall survival (OS) and progression-free survival (PFS) was evaluated by the Cox proportional hazards model in a 12 month-landmark analysis.

Results:
Out of 16,703 patients in the ESME database, 1977 had stage IV MBC at diagnosis, were alive and progression-free at 12 months and eligible for this study. Among them, 530 (26.8%) had received primary breast cancer surgery within 12 months. A greater proportion of patients who received surgery had less than 3 metastatic sites than the no-surgery group (90.8% vs 78.2%, P < 0.0001). Surgery within 12 months was associated with treatment with chemotherapy, HER2-targeted therapy (89.1% vs 69.6%, P < 0.0001) and locoregional radiotherapy (81.7% vs 32.5%, P < 0.0001). Multivariable analyses showed that surgery performed within 12 months was associated with longer OS and PFS (adjusted HR [95%CI] = 0.75 [0.61–0.92] and 0.72 [0.63–0.83], respectively), which were also affected by pattern and number of metastatic sites, histological subtype, and age.

Conclusions:
In the large ESME cohort, surgery within 1 year after de novo MBC diagnosis was associated with a significantly better OS and PFS.
Preoperative Heart Failure Treatment Prevents Postoperative Cardiac Complications in Patients With Lower Risk
Authors: Shay Denys , Ng Pauline Y. , Dudzinski David M. , Grabitz Stephanie D. , Mitchell John D. , Xu Xinling , Houle Timothy T. , Bhatt Deepak L. , Eikermann Matthias 
Published: February 2021

Objective:
The objective of this study was to identify undertreated subgroups of patients with heart failure who would benefit from better perioperative optimization.

Summary of Background Data:
Patients with heart failure have increased risks of postoperative cardiac complications after noncardiac surgery.

Methods:
In this analysis of hospital registry data of 130,677 patients undergoing noncardiac surgery, the exposure was preoperative history of heart failure. The outcome, cardiac complications, was defined as a composite of myocardial infarction, cardiac arrest, acute heart failure, and mortality within 30 postoperative days.

Results:
History of heart failure (n = 10,256; 7.9%) was associated with increased risk of cardiac complications [8.1% vs 1.1%; adjusted odds ratio, 2.28 (95% CI, 2.02–2.56); P < 0.001). Patients with heart failure and who carried a lower risk profile had increased risks of postoperative cardiac complications secondary to heart failure [adjusted absolute risk difference, 1.7% (95% CI, 1.4%–2.0%, lower risk); P < 0.001 vs 0.5% (95% CI, –0.6% to 1.6%, higher risk); P = 0.38]. Patients with heart failure and lower risk received a lower level of health care utilization preoperatively, and less frequently received anti-heart failure medications (59% vs 72% and 61% vs 82%; both P < 0.001). These preventive therapies significantly decreased the risk of cardiac complications in patients with heart failure.

Conclusions:
In patients with heart failure who have a lower preoperative risk profile, clinicians often make insufficient attempts to optimize their clinical condition preoperatively. Preoperative preventive treatment reduces the risk of postoperative cardiac complications in these lower-risk patients with heart failure.
Financial Evaluation of Kidney Transplant With Hepatitis C Viremic Donors to Uninfected Recipients
Authors: Axelrod David A. , Lentine Krista L. , Balakrishnan Ramji , Chang Su-Hsin , Alhamad Terek , Xiao Huiling , Kasiske Bertran L. , Bloom Roy D. , Schnitzler Mark A. 
Published: February 2021

Background.
Kidney transplantation with hepatitis C viremic (dHCV+) donors appears safe for recipients without HCV when accompanied by direct acting antiviral (DAA) treatment. However, US programs have been reluctant to embrace this approach due to concern about insurance coverage. While the cost of DAA treatment is currently offset by the reduction in waiting time, increased competition for dHCV+ organs may reduce this advantage. This analysis sought to demonstrate the financial benefit of dHCV+ transplant for third-party health insurers to expand coverage availability.

Methods.
An economic analysis was developed using a Markov model for 2 decisions: first, to accept a dHCV+ organ versus wait for a dHCV uninfected organ; or second, accept a high kidney donor profile index (KDPI) (>85) organ versus wait for a better quality dHCV+ organ. The analysis used Medicare payments, historical survival data, cost report data, and an estimated cost of DAA of $29 874.

Results.
In the first analysis, using dHCV+ kidneys reduced the cost of end-stage kidney disease care if the wait for a dHCV uninfected organ exceeded 11.5 months. The financial breakeven point differed according to the cost of DAA treatment. In the second analysis, declining a high-KDPI organ in favor of a waiting dHCV+ organ was marginally clinically beneficial if waiting times were <12 months but not cost effective.

Conclusions.
dHCV+ transplant appears to be economically and clinically advantageous compared with waiting for dHCV-uninfected transplant but should not replace high-KDPI transplant when appropriate. Despite the high cost of DAA therapy, health insurers benefit financially from dHCV+ transplant within 1 year.
New-Onset Gout as an Independent Risk Factor for Returning to Dialysis After Kidney Transplantation
Authors: Li Justin W. , Yin David , Wang Zheng , Brigham Mark D. , LaMoreaux Brian D. , Kent Jeffrey D. , Francis-Sedlak Megan , Johnson Richard J. , Hadker Nandini , Francis Kevin M. , Sanchez Herman A. , Miyasato Gavin 
Published: February 2021

Background.
The causal relationship between gout and renal transplant outcomes is difficult to assess due to multiple interacting covariates. This study sought to estimate the independent effect of new-onset gout on renal transplant outcomes using a methodology that accounted for these interactions.

Methods.
This study analyzed data on patients in the US Renal Data System (USRDS) who received a primary kidney transplant between 2008 and 2015. The exposure was new-onset gout, and the primary endpoint was returning to dialysis >12 months postindex date (transplant date). A marginal structural model (MSM) was fitted to determine the relative risk of new-onset gout on return to dialysis.

Results.
18 525 kidney transplant recipients in the USRDS met study eligibility. One thousand three hundred ninety-nine (7.6%) patients developed new-onset gout, and 1420 (7.7%) returned to dialysis >12 months postindex. Adjusting for baseline and time-varying confounders via the MSM showed new-onset gout was associated with a 51% increased risk of return to (RR, 1.51; 95% CI, 1.03-2.20).

Conclusions.
This finding suggests that new onset gout after kidney transplantation could be a harbinger for poor renal outcomes, and to our knowledge is the first study of kidney transplant outcomes using a technique that accounted for the dynamic relationship between renal dysfunction and gout.
Liver-only Transplantation in a Patient With Complex Congenital Heart Disease: Case Report and Review of the Literature
Authors: Perquy David , Pirenne Jacques , Van De Bruaene Alexander , Rex Steffen , van Malenstein Hannah 
Published: February 2021

Background.
Patients with liver failure due to or in addition to congenital heart disease (CHD) represent a growing population in need of organ transplantation. Traditionally, these patients received a combined heart and liver transplantation carrying a high risk of perioperative morbidity and mortality.

Methods.
We discuss a patient with complex cyanotic CHD and biliary atresia undergoing liver-only transplantation. Furthermore, a literature study was performed on combined congenital heart and liver disease in the setting of transplantation.

Results.
We describe a unique case of a patient with severe CHD undergoing orthotopic liver transplantation for biliary atresia. In the literature, congenital malformations affecting different organs seems not that infrequent. Liver-only transplantation has been described in mild CHD, although data in adult patients are scarce. In severe CHD, the liver usually suffers from congestion. The severity of liver disease and reversibility should be estimated to decide on combined heart-liver transplantation.

Conclusions.
Our case and a review of the literature demonstrate that a patient-tailored approach with liver-only transplantation may be an appropriate alternative to combined heart and liver transplantation in selected cases.
Evaluating the Associations Between the Liver Frailty Index and Karnofsky Performance Status With Waitlist Mortality
Authors: Xu Chelsea Q. , Yao Frederick , Mohamad Yara , Wong Randi , Kent Dorothea , Seetharaman Srilakshmi , Srisengfa Yanin , Lai Jennifer C. 
Published: February 2021

Background.
Frailty has emerged as a critical determinant of mortality in patients with cirrhosis. Currently, the United Network for Organ Sharing registry only includes the Karnofsky Performance Status (KPS) scale, which captures a single component of frailty. We determined the associations between frailty, as measured by the Liver Frailty Index (LFI), and KPS with waitlist mortality.

Methods.
Included were 247 adult patients with cirrhosis listed for liver transplantation without hepatocellular carcinoma from February 2014 to June 2019, who underwent outpatient assessments using the LFI and KPS within 30 days of listing. “Frail” was defined using the established LFI cutoff of ≥4.4. Competing risk models assessed associations between the LFI and KPS with waitlist mortality (death/delisting for sickness).

Results.
At a median 8 months follow-up, 25 (10%) patients died/were delisted. In this cohort, median Model for End-Stage Liver Disease-Sodium was 17, LFI was 3.9 (interquartile range 3.4–4.5), and KPS was 80 (interquartile range 70–90). In multivariable analysis, LFI (sub-hazard ratio 1.07, per 0.1 unit; 95% confidence interval, 1.01-1.12) was associated with waitlist mortality while KPS was not (sub-hazard ratio 1.00, per 10 units; 95% confidence interval, 0.78-1.29).

Conclusions.
Our data suggest that frailty, as measured by the LFI, may be more appropriate at capturing mortality risk than KPS and provide evidence in support of using the LFI more broadly in clinical transplant practice in the outpatient setting.
Precision Medicine in Kidney Transplantation: Just Hype or a Realistic Hope?
Authors: Nobakht Ehsan , Jagadeesan Muralidharan , Paul Rohan , Bromberg Jonathan , Dadgar Sherry 
Published: February 2021

Abstract.
Desirable outcomes including rejection- and infection-free kidney transplantation are not guaranteed despite current strategies for immunosuppression and using prophylactic antimicrobial medications. Graft survival depends on factors beyond human leukocyte antigen matching such as the level of immunosuppression, infections, and management of other comorbidities. Risk stratification of transplant patients based on predisposing genetic modifiers and applying precision pharmacotherapy may help improving the transplant outcomes. Unlike certain fields such as oncology in which consistent attempts are being carried out to move away from the “error and trial approach,” transplant medicine is lagging behind in implementing personalized immunosuppressive therapy. The need for maintaining a precarious balance between underimmunosuppression and overimmunosuppression coupled with adverse effects of medications calls for a gene-based guidance for precision pharmacotherapy in transplantation. Technologic advances in molecular genetics have led to increased accessibility of genetic tests at a reduced cost and have set the stage for widespread use of gene-based therapies in clinical care. Evidence-based guidelines available for precision pharmacotherapy have been proposed, including guidelines from Clinical Pharmacogenetics Implementation Consortium, the Pharmacogenomics Knowledge Base National Institute of General Medical Sciences of the National Institutes of Health, and the US Food and Drug Administration. In this review, we discuss the implications of pharmacogenetics and potential role for genetic variants-based risk stratification in kidney transplantation. A single score that provides overall genetic risk, a polygenic risk score, can be achieved by combining of allograft rejection/loss-associated variants carried by an individual and integrated into practice after clinical validation.
Ageing with schizophrenia: an update
Authors: Solomon Haley V. , Sinopoli Martina , DeLisi Lynn E. 
Published: February 2021

Purpose of review
The aim of this review was to summarize the recent literature on the clinical symptoms, functioning, outcomes and treatments for older adults with chronic schizophrenia.

Recent findings
The number and proportion of older adults with schizophrenia is rapidly increasing. Schizophrenia is a heterogeneous disorder and older adults with schizophrenia display significant variability in symptom severity, quality of life and overall outcomes. Many achieve stable disease remission, some display persistent nonremission and others experience fluctuating symptoms. Depression is commonly reported, and although rates of suicide are higher when compared with age-matched peers, the excess mortality seen in this population is mainly attributed to natural causes of death. Cognitive decline and reduced illness awareness have important implications for functional status and quality of life. Antipsychotics remain essential in the treatment regimen, although elderly patients with chronic disease may be good candidates for gradual dose reduction. Interdisciplinary treatment approaches as well as nonpharmacologic psychosocial interventions play a critical adjunctive role in the treatment of older adults with schizophrenia.

Summary
Research focusing on schizophrenia in late life is sparse. Too often, older patients are eliminated from research studies or averaged in with all age groups. Thus, there continues to be gaps in our understanding of modifiable predictors of remission and recovery, and the most efficacious and safest treatment approaches for this age group.
Neuron-derived extracellular vesicles extracted from plasma show altered size and miRNA cargo as a function of antidepressant drug response
Authors: Saeedi Saumeh , Nagy Corina , Théroux Jean-Francois , Wakid Marina , Fiori Laura M. , Ibrahim Pascal , Yang Jennie , Rotzinger Susan , Foster Jane A. , Mechawar Naguib , Kennedy Sidney H. , Turecki Gustavo 
Published: February 2021

AbstractPrevious work has demonstrated that microRNAs (miRNAs) change as a function of antidepressant treatment (ADT) response. However, it is unclear how representative these peripherally detected miRNA changes are to those occurring in the brain. This study aimed to use peripherally extracted neuron-derived extracellular vesicles (NDEVs) to circumvent these limitations and investigate neuronal miRNA changes associated with antidepressant response. Samples were collected at two time points (baseline and after 8 weeks of follow-up) from depressed patients who responded (N=20) and did not respond (N=20) to escitalopram treatment, as well as controls (N=20). Total extracellular vesicles (EVs) were extracted from plasma, and then further enriched for NDEVs by immunoprecipitation with L1CAM. EV size was measured using tunable resistive pulse sensing, and NDEV miRNA cargo was extracted and sequenced. Subsequently, studies in cell lines and postmortem tissue were conducted. Characterization of NDEVs revealed they were smaller than other EVs isolated from plasma (p<0.0001), had brain-specific neuronal markers, and contained miRNAs enriched for brain functions (p<0.0001) Furthermore, NDEVs from depressed patients were smaller than controls (p<0.05), and NDEV size increased with ADT response (p<0.01). Finally, changes in NDEV cargo, specifically changes in miR-21-5p, miR-30d-5p and miR-486-5p together (p<0.01), were associated with ADT response. Targets of these three miRNAs were altered in brain tissue from depressed individuals (p<0.05). Together, this study indicates that changes in peripherally isolated NDEVs can act as both a clinically accessible and informative biomarker of ADT response specifically through size and cargo.
Pulsed Focal ultrasound as a non-invasive method to deliver exosomes in the brain/stroke
Authors: Alptekin Ahmet , Khan Mohammad B , Ara Roxan , Rashid Mohammad H , Kong Fengchong , Parvin Mahrima , Frank Joseph A , Chopra Rajiv , Dhandapani Krishnan , Arbab Ali S. 
Published: February 2021

AbstractExosomes, a component of extracellular vesicles are shown to carry important small RNAs, mRNAs, protein, and bioactive lipid from parent cells and are found in most biological fluids. Investigators have demonstrated the importance of mesenchymal stem cells (MSCs) derived exosomes in repairing stroke lesions. However, exosomes from endothelial progenitor cells (EPCs) have not been tested in any stroke model nor has there been an evaluation of whether these exosomes target/home to areas of pathology. Targeted delivery of IV administered exosomes has been a great challenge and a targeted delivery system is lacking todeliver naïve (unmodified) exosomesfrom EPCs to the site of interest. Pulsed focused ultrasound (pFUS) is being used for therapeutic and experimental purposes. There has not been any report showing the use of pulsed low-intensity pFUS to deliver exosomes to the site of interest in models of stroke. In this proof of principle study, we have shown different parameters of pFUS to deliver exosomes in the intact and stroke brain with or without IV administration of nanobubbles. The study results showed that administration of nanobubbles is detrimental to the brain structures (micro bleeding and white matter destruction) at peak negative pressure (PNP) of >0.25 MPa, despite enhanced delivery of IV administered exosomes. However, without nanobubbles, pFUS PNP = 1 to 2 MPa enhances the delivery of exosomes in the stroke area without altering the brain structures.
Insertions and deletions as phylogenetic signal in an alignment-free context
Authors: Birth Niklas , Dencker Thomas , Morgenstern Burkhard 
Published: February 2021

AbstractMost methods for phylogenetic tree reconstruction are based on sequence alignments; they infer phylogenies from substitutions that may have occurred at the aligned sequence positions. Gaps in alignments are usually not employed as phylogenetic signal. In this paper, we explore an alignment-free approach that uses insertions and deletions (indels) as an additional source of information for phylogeny inference. For a set of four or more input sequences, we generate so-calledquartet blocksof four putative homologous segments each. Forpairsof such quartet blocks involving the same four sequences, we compare the distances between the two blocks in these sequences, to obtain hints about indels that may have happened between the blocks since the respective four sequences have evolved from their last common ancestor. A prototype implementation is presented to infer phylogenetic trees from these data, using aquartet-treeapproach or, alternatively, under themaximum-parsimonyparadigm. This approach should not be regarded as an alternative to established methods, but rather as a complementary source of phylogenetic information. Interestingly, however, our software is able to produce phylogenetic trees from putative indels alone that are comparable to trees obtained with existing alignment-free methods.