bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial
Authors: Musa Ahmed M , Mbui Jane , Mohammed Rezika , Olobo Joseph , Ritmeijer Koert , Alcoba Gabriel , Muthoni Ouattara Gina , Egondi Thaddaeus , Nakanwagi Prossy , Omollo Truphosa , Wasunna Monique , Verrest Luka , Dorlo Thomas P C , Musa Younis Brima , Nour Ali , Taha Ahmed Elmukashfi Elmukashfi , Ismail Omer Haroun Ahmed , Khalil Eltahir A G , Njenga Simon , Fikre Helina , Mekonnen Tigist , Mersha Dagnew , Sisay Kasaye , Sagaki Patrick , Alvar Jorge , Solomos Alexandra , Alves Fabiana 
Published: September 2022

Abstract

Background
This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa.

Methods
An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months.

Results
Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], −6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, −0.3%; 97.5% CI, –7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug–related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (&lt;12 years) and adults.

Conclusions
PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa.

Clinical Trials Registration
NCT03129646.
Transmission of Carbapenem-Resistant Klebsiella pneumoniae in US Hospitals
Authors: Luterbach Courtney L , Chen Liang , Komarow Lauren , Ostrowsky Belinda , Kaye Keith S , Hanson Blake , Arias Cesar A , Desai Samit , Gallagher Jason C , Novick Elizabeth , Pagkalinawan Stephen , Lautenbach Ebbing , Wortmann Glenn , Kalayjian Robert C , Eilertson Brandon , Farrell John J , McCarty Todd , Hill Carol , Fowler Vance G , Kreiswirth Barry N , Bonomo Robert A , van Duin David ,   for the Multi-Drug Resistant Organism Network Investigators Network Investigators and the Antibacterial Resistance Leadership Group
Published: September 2022

Abstract

Background
Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals.

Methods
From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster.

Results
Most patients were admitted from home (n = 150, 43%) or long-term care facilities (n = 115, 33%). Urine (n = 149, 43%) was the most common isolation site. Overall, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. Approximately half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intrasystem and 22 (40%) intersystem clusters. Dynamic clusters consisted of 32 (68%) intrasystem and 15 (32%) intersystem clusters and had fewer SNP differences than static clusters (8 vs 9; P = .045; 95% confidence interval [CI]: −4 to 0). Dynamic intersystem clusters contained more patients than dynamic intrasystem clusters (median [interquartile range], 4 [2, 7] vs 2 [2, 2]; P = .007; 95% CI: −3 to 0).

Conclusions
Widespread intrasystem and intersystem transmission of CRKp was identified in hospitalized US patients. Use of different methods for assessing genetic similarity resulted in only minor differences in interpretation.
Predictors and outcome of electrical storm–induced cardiogenic shock
Authors: Incognito Cameron , Martens Pieter , Hedley Jeffrey , Parker Joshua D , Posadas Kristine , Gangidi Shravani , Wazni Oussama , Menon Venu , Rickard John , Hussein Ayman , Tang Wai Hong Wilson 
Published: September 2022

Abstract

Aim
Limited information is available about the short- and long-term outcomes in electrical storm (ES)-induced cardiogenic shock (CS) and its predictors.

Methods and results
This is a retrospective, single-centre cohort study of consecutive patients with ES admitted to the Cardiac Intensive Care Unit between 2015 and 2020. The proportion of ES patients who developed CS was adjudicated, and clinical predictors of in-hospital ventricular arrhythmia (VA)-related mortality and 1-year all-cause mortality were investigated. Of the 214 patients with ES, 33.6% developed CS. Left-ventricular ejection fraction, admission lactate, absence of an implantable cardioverter defibrillator, and admission central venous pressure were independently associated with development of CS (P &lt; 0.03 for all). Based on these variables, a FLIC score was developed (https://riskcalc.org/FLICscore/) to predict ES-induced CS [area under the curve (AUC) = 0.949, with AUC = 0.954 in a validation cohort, both P &lt; 0.001]. Patients who developed CS had a 11.3-fold [95% confidence interval (CI) 2.7–12.8] increased odds for in-hospital VA-related mortality and 9.4-fold (95% CI 4.0–22.4) increased odds for in-hospital all-cause mortality. A FLIC score above 0.62 was associated with a 6.2- and 5.8-fold increased odds for respectively similar endpoints. Patients with ES-induced CS received more treatment modalities to manage the ES (4.5 ± 1.8 vs. 2.3 ± 1.2, P &lt; 0.001) and had longer length of stay [14 (8–27) vs. 8 (5–13), P &lt; 0.001] than patients without CS. Interestingly, if patients with ES-induced CS survived to discharge, their outcomes were similar to those without CS at 1 year.

Conclusion
Cardiogenic shock in ES is a frequent and potentially life-threatening complication with high short-term mortality. A novel risk score could identify patient at risk, generating a potential for early risk-based interventions.
A novel predictive model for distinguishing mediastinal lymphomas from thymic epithelial tumours
Authors: Wang Shuai , Lin Miao , Yang Xinyu , Lin Zhenyang , Wang Siyang , Jiang Jiahao , Chen Gang , Ao Yongqiang , Gao Jian , Shi Hongcheng , Cheng Luya , Ding Jianyong 
Published: September 2022

Abstract

OBJECTIVES
We recently reported a high rate of nontherapeutic thymectomy. Mediastinal lymphomas (MLs) are the malignancies most likely to be confused with thymic epithelial tumours (TETs). This study aimed to establish a predictive model by evaluating clinical variables and positron emission tomography to distinguish those diseases.

METHODS
From 2018 to 2021, consecutive patients who were pathologically diagnosed with TETs or MLs were retrospectively reviewed. Univariable and multivariable analyses were used to identify association factors. The Akaike information criterion was used to select variables. A nomogram was developed and validated to differentiate MLs from TETs.

RESULTS
A total of 198 patients were included. Compared with TETs, patients with MLs were more likely to be younger with higher metabolic tumour volume (154.1 vs 74.6 cm3), total lesion glycolysis (1388.8 vs 315.2 g/ml cm3), SUVmean (9.2 vs 4.8), SUVpeak (12.9 vs 6.3) and SUVmax (14.8 vs 7.5). A nomogram was established based on the stepwise regression results and the final model containing age and SUVmax had minimal Akaike information criterion value of 72.28. Receiver operating characteristic analyses indicated that the area under the curve of predictive nomogram in differentiating MLs from TETs was 0.842 (95% CI: 0.754–0.907). The internal bootstrap resampling and calibration plots demonstrated good consistence between the prediction and the observation.

CONCLUSIONS
Combination of age and SUVmax appears to be a useful tool to differentiate MLs from TETs. The novel predictive model prevents more patients from receiving nontherapeutic thymectomy.
Assessing sex-based differences in postsurgical clinical outcomes after use of del Nido cardioplegia
Authors: Honzel Emily , Nemeth Samantha , Kazzi Brigitte E , Kossar Alexander P , Sun Jocelyn , Kaku Yuji , Takeda Koji , Takayama Hiroo , Argenziano Michael , Spellman Jessica , Miltiades Andrea , Fung Kenmond , Beck James , Smith Craig R , Kurlansky Paul , George Isaac 
Published: September 2022

AbstractCreated with BioRender.com.OBJECTIVESdel Nido cardioplegia is used to pharmacologically arrest the heart during cardiac surgery and decrease reperfusion- and ischaemia-related myocardial injury. Studies have demonstrated the physiological differences between male and female hearts, potentially related to cardiac size or myocyte calcium handling; we aimed to assess for between-sex differences in clinical outcomes after receipt of del Nido cardioplegia.METHODSPatients who underwent coronary artery bypass or coronary artery bypass graft/valve surgery at our institution using del Nido cardioplegia (January 2014 to December 2019) were included (n = 2118). Clinical data were collected retrospectively. After the creation of a propensity-matched cohort (n = 1252), multivariable logistic regression was used to analyse binary postoperative outcomes, and a Gamma model was used for a continuous postoperative outcome. Our primary end-point was a composite end-point comprised of 30-day mortality and/or need for a post-bypass mechanical support device.RESULTSThe final cohort included 459 females and 793 males (matched up to 1:2, all standardized mean differences &lt;0.1). Multivariable logistic regression showed that biological sex was not associated with the composite primary end-point (odds ratio = 0.898, P = 0.779). A Gamma model indicated that there were no sex-related differences in vasoactive-inotropic scores reflecting vasopressor and inotrope usage at the time of patient operating room exit (exp[est] = 1.394, P = 0.189).CONCLUSIONSOur findings showed no significant between-sex differences in clinical outcomes after receiving del Nido cardioplegia, suggesting adequate myocardial protection as currently administered. Further research is warranted to elicit if there are sex-based differences between cardioplegic solutions.IRB APPROVAL DATE (PROTOCOL NUMBER)26 May 2021 (AAAR8359).
Reproducibility of ventricular arrhythmias at exercise testing for prediction of non-ischaemic left ventricular scar in athletes
Authors: Brunetti Giulia , Graziano Francesca , Cavigli Luna , Cipriani Alberto , D’Ascenzi Flavio , Bauce Barbara , Pilichou Kalliopi , Perazzolo Marra Martina , Corrado Domenico , Zorzi Alessandro 
Published: September 2022

AbstractAimsThe non-ischaemic left ventricular scar (NILVS) is an emerging substrate of ventricular arrhythmias (VA) in the athlete. We tested the diagnostic value of VA reproducibility at repeated exercise testing (ET).Methods and resultsWe included consecutive athletes who underwent cardiac magnetic resonance (CMR) for evaluation of VA and two consecutive ET off-therapy within 12 months. Those with a positive family history of premature sudden death/cardiomyopathy, syncope/pre-syncope, ECG or echocardiography abnormalities, or low-risk VA (exercise-suppressed infundibular or fascicular VA) were excluded. The NILVS was defined as subepicardial/midmyocardial stria of late gadolinium enhancement involving &gt;5% of the LV mass. Reproducibility was defined as the occurrence of VA with the same pattern and behaviour during repeated ET. Of 325 athletes who underwent CMR for evaluation of VA, 75 were included, and 30 showed NILVS involving three [2–4] LV segments. At first ET, athletes with NILVS showed a higher prevalence of exercise-induced VA (93% vs. 53%, P &lt; 0.001), while other VA characteristics did not differ between groups. At repeated ET, reproducibility was observed in 97% of athletes with vs. 13% without NILVS (P &lt; 0.001). The remaining 87% of athletes with normal CMR either did not show any VA at repeated ET (59%) or showed arrhythmias with different patterns, mostly infundibular. Reproducibility yielded a positive predictive value for NILVS of 83% and a negative predictive value of 98%.ConclusionVA reproducibility at repeated ET predicted an underlying NILVS in athletes with VA and otherwise normal clinical work-up. This finding may improve risk stratification and appropriate CMR referral of athletes with apparently idiopathic VA.
Long-term outcomes of left atrial appendage isolation using cryoballoon in persistent atrial fibrillation
Authors: Yorgun Hikmet , Şener Yusuf Ziya , Tanese Nikita , Keresteci Ahmet , Sezenöz Burak , Çöteli Cem , Ateş Ahmet Hakan , Boveda Serge , Aytemir Kudret 
Published: September 2022

AbstractAimsThere is an increasing trend evaluating the role of non-pulmonary vein (PV) triggers to improve ablation outcomes in persistent atrial fibrillation (AF) as pulmonary vein isolation (PVI) strategy alone has modest outcomes. We investigated the long-term safety and efficacy of left atrial appendage isolation (LAAi) in addition to PVI using cryoballoon (CB) in persistent AF.Methods and resultsIn this multicentre retrospective analysis, we included a total of 193 persistent AF patients (mean age: 60 ± 11 years, 50.3% females) who underwent PVI and LAAi using CB. Baseline and follow-up data including electrocardiography (ECG), 24 h Holter ECGs, and echocardiography were recorded for all patients. Atrial tachyarrhythmia (ATa) recurrence was defined as the detection of AF, atrial flutter, or atrial tachycardia (≥30 s) after a 3-month blanking period. At a median follow-up of 55 (36.5–60.0) months, 85 (67.9%) patients with PVI + LAAi were in sinus rhythm after the index procedure. Ischaemic stroke/transient ischemic attack occurred in 14 (7.2%) patients at a median of 24 (2–53) months following catheter ablation. Multivariate regression analysis revealed heart failure with preserved ejection fraction [hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.04–5.02; P = 0.038], male gender (HR 0.53, 95% CI 0.29–0.96; P = 0.037), and LA area (HR 1.04, 95% CI 0.53–1.32; P = 0.023) as independent predictors of ATa recurrence.ConclusionOur findings demonstrated that the LAAi + PVI strategy using CB had acceptable long-term outcomes in patients with persistent AF. Systemic thrombo-embolic events are an important concern throughout the follow-up, which were mostly observed in case of non-adherence to anticoagulants.
SID-4/NCK-1 is important for dsRNA import in Caenorhabditis elegans
Authors: Bhatia Sonya , Hunter Craig P 
Published: September 2022

Abstract
RNA interference is sequence-specific gene silencing triggered by double-stranded RNA. Systemic RNA interference is where double-stranded RNA, expressed or introduced into 1 cell, is transported to and initiates RNA interference in other cells. Systemic RNA interference is very efficient in Caenorhabditis elegans and genetic screens for systemic RNA interference-defective mutants have identified RNA transporters (SID-1, SID-2, and SID-5) and a signaling protein (SID-3). Here, we report that SID-4 is nck-1, a C. elegans NCK-like adaptor protein. sid-4 null mutations cause a weak, dose-sensitive, systemic RNA interference defect and can be effectively rescued by SID-4 expression in target tissues only, implying a role in double-stranded RNA import. SID-4 and SID-3 (ACK-1 kinase) homologs interact in mammals and insects, suggesting that they may function in a common signaling pathway; however, a sid-3; sid-4 double mutants showed additive resistance to RNA interference, suggesting that these proteins likely interact with other signaling pathways as well. A bioinformatic screen coupled to RNA interference sensitivity tests identified 23 additional signaling components with weak RNA interference-defective phenotypes. These observations suggest that environmental conditions may modulate systemic RNA interference efficacy, and indeed, sid-3 and sid-4 are required for growth temperature effects on systemic RNA interference silencing efficiency.
Interpreting convolutional neural network decision for earthquake detection with feature map visualization, backward optimization and layer-wise relevance propagation methods
Authors: Majstorović Josipa , Giffard-Roisin Sophie , Poli Piero 
Published: September 2022

SUMMARY
In the recent years, the seismological community has adopted deep learning (DL) models for many diverse tasks such as discrimination and classification of seismic events, identification of P- and S-phase wave arrivals or earthquake early warning systems. Numerous models recently developed are showing high accuracy values, and it has been attested for several tasks that DL models perform better than the classical seismological state-of-art models. However, their performances strongly depend on the DL architecture, the training hyperparameters, and the training data sets. Moreover, due to their complex nature, we are unable to understand how the model is learning and therefore how it is making a prediction. Thus, DL models are usually referred to as a ‘black-box’. In this study, we propose to apply three complementary techniques to address the interpretability of a convolutional neural network (CNN) model for the earthquake detection. The implemented techniques are: feature map visualization, backward optimization and layer-wise relevance propagation. Since our model reaches a good accuracy performance (97%), we can suppose that the CNN detector model extracts relevant characteristics from the data, however a question remains: can we identify these characteristics? The proposed techniques help to answer the following questions: How is an earthquake processed by a CNN model? What is the optimal earthquake signal according to a CNN? Which parts of the earthquake signal are more relevant for the model to correctly classify an earthquake sample? The answer to these questions help understand why the model works and where it might fail, and whether the model is designed well for the predefined task. The CNN used in this study had been trained for single-station detection, where an input sample is a 25 s three-component waveform. The model outputs a binary target: earthquake (positive) or noise (negative) class. The training database contains a balanced number of samples from both classes. Our results shows that the CNN model correctly learned to recognize where is the earthquake within the sample window, even though the position of the earthquake in the window is not explicitly given during the training. Moreover, we give insights on how a neural network builds its decision process: while some aspects can be linked to clear physical characteristics, such as the frequency content and the P and S waves, we also see how different a DL detection is compared to a visual expertise or an STA/LTA detection. On top of improving our model designs, we also think that understanding how such models work, how they perceive an earthquake, can be useful for the comprehension of events that are not fully understood yet such as tremors or low frequency earthquakes.
Systematic review of digital interventions to support refusal self-efficacy in child and adolescent health promotion
Authors: Nyman Johanna , Tornivuori Anna , Salanterä Sanna , Barroso Teresa , Parisod Heidi 
Published: September 2022

Summary
Refusal self-efficacy protects against risky health behavior. Digital interventions have the potential to support self-efficacy due to the enactive experience provided by digital technologies. The aim of this systematic literature review was to evaluate the evidence of digital interventions to support refusal self-efficacy in child and adolescent health promotion. Following the Cochrane Collaboration guidelines, five electronic databases were searched from 2009 to 2020. The studies were assessed by two independent reviewers according to the eligibility criteria. Eligible studies were included in the review, assessed for risk of bias, synthesized narratively and assessed for evidence quality with the GRADE approach. Twenty-three studies, that examined 18 different interventions, were included in the review. The interventions included various digital elements as means to support the child and adolescent refusal self-efficacy (e.g. games, videos, feedback and activities for regulating feelings). The interventions improving refusal self-efficacy were more often used at home setting and addressed the four sources of self-efficacy with different digital elements regardless of intervention duration and intensity. Although the results on intervention effects varied and the evidence quality remained low, the overall evidence concerning these interventions was encouraging. Based on the subgroup analysis, the results were mainly encouraging among girls. When these interventions are implemented in health promotion, their benefits and weaknesses need to be considered comprehensively. The results provide information for designing and developing digital interventions to support child and adolescent refusal self-efficacy. Further research with larger sample sizes and more rigorous study designs is needed to strengthen the evidence of these interventions.
Comprehensive school health: teachers’ perceptions and implementation of classroom physical activity breaks in US schools
Authors: Barcelona Jeanne , Centeio Erin , Phillips Sharon , Gleeson Dara , Mercier Kevin , Foley John , Simonton Kelly , Garn Alex 
Published: September 2022

Summary
Modifications to the social–ecological model, such as Whole School, Whole Community, Whole Child (WSCC) frameworks, have been utilized in comprehensive school health interventions. Classroom physical activity breaks are used when implementing whole-of-school approaches. However, the onus to implement classroom physical activity breaks is on school stakeholders. This study aimed to explore teacher and principal perceptions and implementation of physical activity breaks in elementary schools. Further, this study investigated how theoretical factors representative of the social–ecological model and their interactions affect teacher and principal perceptions and utilization of classroom physical activity breaks. Interviews were conducted to understand teacher and principal perceptions and implementation. A total of 12 classroom teachers and five principals participated in semi-structured interviews which were analyzed using constant comparison and deductive analysis to identify relationships and themes coded across the social–ecological and WSCC models. To ensure fidelity individuals that led the professional development (n = 2) were also interviewed. Three main themes emerged as part of the data analysis: (i) The Connection Between Intrapersonal Knowledge and Interpersonal Professional Development, (ii) Resources, Sharing Means Caring and (iii) The Policy Level Creates Time. Teachers and principals valued knowledge and resources and felt that policy facilitated implementation. Results suggest that classroom physical activity breaks are influenced by multiple factors across varied levels of the social–ecological model. Understanding this relationship can inform future professional development to increase the provision of classroom physical activity breaks among teachers.