bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bivalirudin or Unfractionated Heparin for Anticoagulation in Pediatric Patients on Continuous Flow Ventricular Assist Device Support: Single-Center Retrospective Cohort Study
Authors: Puri Kriti , Tunuguntla Hari P. , Hensch Lisa A. , Loh JiaHoi , Hui Shiu-Ki , Razavi Asma , Tume Sebastian C. , Humlicek Timothy J. , Denfield Susan W. , Spinner Joseph A. , Choudhry Swati , Price Jack F. , Dreyer William J. , Adachi Iki , Teruya Jun 
Published: June 2022

Objectives:
Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited.

Design:
Retrospective cohort study.

Setting:
Single tertiary-quaternary referral center.

Patients:
All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020.

Interventions:
Not applicable.

Measurements and Main Results:
Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09–0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47–13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a “washout” in eight cases with concern for pump thrombosis—six had resolution of the pump thrombosis, while two needed pump exchange.

Conclusions:
Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin “washout” was successful in medical management of six of eight cases of possible pump thrombosis.
Exploratory Use of Glycoprotein IIb/IIIa Inhibition in Prevention of Blalock-Taussig Shunt Thrombosis*
Authors: Piekarski Breanna L. , Rogers Jenna , Zurakowski David , Thiagarajan Ravi , Emani Sitaram M. 
Published: June 2022

OBJECTIVES:
Morbidity and mortality related to modified Blalock-Taussig shunt (mBTTS) thrombosis remain a significant risk. Platelet inhibition following mBTTS may reduce this risk. However, oral antiplatelet agents have variable absorption following surgery. We determine risk factors for mBTTS thrombosis and hypothesize that IV glycoprotein IIb/IIIa inhibitor (tirofiban) as a bridge to oral aspirin reduces the rate of shunt thrombosis in the immediate postoperative period. End points within the 14-day follow-up period include mBTTS thrombosis, overall thrombosis, bleeding, length of stay, and mortality.

DESIGN:
Retrospective, Institutional Review Board–approved cohort study.

SETTING:
Single-center cardiac ICU.

PATIENTS:
Patients under the age of 18 who had an mBTTS placed within the study period of January 2008 to December 2018 were included.

INTERVENTIONS:
Patients were divided into two groups: standard of care (SOC) anticoagulation alone and SOC with tirofiban as a bridge to oral aspirin.

MEASUREMENTS and MAIN RESULTS:
Freedom from mBTTS thrombosis was estimated using the Kaplan-Meier method. A multivariable predictive model using the four most significant risk factors was developed using logistic regression. A total of 272 patients were included: 36 subjects in the SOC/tirofiban group and 236 in the SOC group. Shunt thrombosis occurred in 26 (11%) SOC group with zero in SOC/tirofiban group (p = 0.03). The median time to thrombosis was 0 days (range, 0–12 d). The area under the curve for the predictive model (anticoagulation group, history of coagulopathy, intraoperative shunt clipping, and shunt size/weight ratio) is 0.790 (p < 0.001). Prevalence of bleeding and mortality was not significantly different between the groups.

CONCLUSIONS:
Highest risk for shunt thrombosis following mBTTS occurs within the first few days after surgical procedure. Tirofiban is a safe addition to SOC and may be an effective strategy to prevent early mBTTS thrombosis.
Predictors of Emergency Department Opioid Use Among Adolescents and Young Adults
Authors: Ruskin Daniel , Rasul Rehana , McCann-Pineo Molly 
Published: June 2022

Objective
It is well established that adolescents and young adults are increasingly vulnerable to the effects of early opioid exposures, with the emergency department (ED) playing a critical role in such introduction. Our objective was to identify predictors of ED opioid administration (ED-RX) and prescribing at discharge (DC-RX) among adolescent and young adults using a machine learning approach.

Methods
We conducted a secondary analysis of ED visit data from the National Hospital Ambulatory Medical Care Survey from 2014 to 2018. Visits where patients were aged 10 to 24 years were included. Predictors of ED-RX and DC-RX were identified via machine learning methods. Separate weighted logistic regressions were performed to determine the association between each predictor, and ED-RX and DC-RX, respectively.

Results
There were 12,693 ED visits identified within the study time frame, with the majority being female (58.6%) and White (70.7%). Approximately 12.3% of all visits were administered an opioid during the ED visit, and 11.5% were prescribed one at discharge. For ED-RX, the strongest predictors were fracture injury (odds ratio [OR], 5.24; 95% confidence interval [CI], 3.73–7.35) and Southern geographic region (OR, 3.01; 95% CI, 2.14–4.22). The use of nonopioid analgesics significantly reduced the odds of ED-RX (OR, 0.46; 95% CI, 0.37–0.57). Fracture injury was also a strong predictor of DC-RX (OR, 5.91; 95% CI, 4.24–8.25), in addition to tooth pain (OR, 5.47; 95% CI, 3.84–7.69).

Conclusions
Machine learning methodologies were able to identify predictors of ED-RX and DC-RX, which can be used to inform ED prescribing guidelines and risk mitigation efforts among adolescents and young adults.
Neuromuscular Electrical Stimulation of Upper Extremities in Patients with Cerebral Palsy: A systematic review and Meta-Analysis of Randomized Controlled Trials
Authors: Ou Chih-Hung , Shiue Chian-Chuan , Kuan Yi-Chun , Liou Tsan-Hon , Chen Hung-Chou , Kuo Ting-Ju 
Published: June 2022

Abstract

Objective
To assess the effects of neuromuscular electrical stimulation on the upper extremities of patients with cerebral palsy.

Design
We searched PubMed, Cochrane, Embase, and Scopus databases for randomized controlled trials examining the effects of neuromuscular electrical stimulation on the upper extremities of children with cerebral palsy.

Results
Eight randomized controlled trials (n = 294) were included in the meta-analysis. Compared with traditional physical therapy, sensorimotor training and task-oriented training, constraint-induced movement therapy, dynamic bracing, and conventional robot-assisted therapy, neuromuscular electrical stimulation in combination with these therapies resulted in significantly greater functional scale scores (standardized mean difference (SMD): 0.80; 95% confidence interval [CI]: 0.54–1.06), muscle strength of upper extremities (SMD: 0.57; 95% CI: 0.25–0.88), and spasticity of upper extremities (relative risk [RR]: 2.53; 95% CI: 1.46–4.39) (SMD: −0.18; 95% CI: −0.29 to −0.06) but did not improve the wrist range of motion (SMD: 0.43; 95% CI: −0.04–0.91). In addition, the effect of neuromuscular electrical stimulation on functional scale scores remained after 3 months of follow-up (SMD: 0.68; 95% CI: 0.16–1.2).

Conclusion
Neuromuscular electrical stimulation effectively improved hand function, muscle strength, and spasticity in patients with cerebral palsy.
Kabul airport suicide bombing attack: Mass casualty management at the EMERGENCY NGO Hospital
Authors: Spagnolello Ornella , Esmati Shekiba , Amiri Abdul Fahim , Shahir Mir Abdul Azim , Gatti Sofia , Portella Gina , Langer Martin 
Published: June 2022

BACKGROUND
Terrorist attacks with large numbers of civilian victims are not uncommon in war-torn countries, and present a unique challenge for health care facilities with limited resources. However, these events are largely underreported and little is known about how the mass casualty events (MCEs) are handled outside of a military setting.

METHODS
This study is a retrospective analysis of the MCE which ensued the Kabul Airport suicide attack (August 26, 2021) at the Kabul EMERGENCY NGO Hospital (Afghanistan).

RESULTS
Within 6 hours, 93 causalities presented at our hospital. Of them, 36 severe injured were admitted. Mean age was 30.8 years (SD, 10.1 years). The most common injury mechanism was shell fragments. The most common injury site was head (63%; 23/36), followed by limbs (55.5%; 20/36) and thoracoabdominal region (30.5%; 11/36). Combined injuries occurred in 38.9% of cases. Patients receiving surgery presented more combined injuries in comparison with patients receiving only medical treatment (47.1% vs. 31.6%). Thoracoabdomen (25.0% vs. 15.4%) and/or extremity injury (42.9% vs. 28.6%) were more prevalent in the surgical group. Thirty major surgical procedures were carried out on 17 patients in the 9 hours following the first arrival. The rate of intensive care unit/high dependency unit admission was 36.1% and the 30-day in-hospital mortality was 16.6% (6/36). All deaths were recorded in the first 24 hours, and none of them received surgery.

CONCLUSION
A large number of wounded patients must be anticipated after suicide bombing attacks. The authors report the challenges faced and key aspects of their management of MCEs.

LEVEL OF EVIDENCE
Prognostic/Epidemiological; Level IV.
The Aedes aegypti peritrophic matrix controls arbovirus vector competence through HPx1, a heme–induced peroxidase
Authors: Talyuli Octavio A. C. , Oliveira Jose Henrique M. , Bottino-Rojas Vanessa , Silveira Gilbert O. , Alvarenga Patricia H. , Kantor Asher M. , Paiva-Silva Gabriela O. , Barillas-Mury Carolina , Oliveira Pedro L. 
Published: June 2022

AbstractAedes aegypti mosquitoes are the main vectors of arboviruses. The peritrophic matrix (PM) is an extracellular layer that surrounds the blood bolus and acts as an immune barrier that prevents direct contact of bacteria with midgut epithelial cells during blood digestion. Here, we describe a heme-dependent peroxidase, hereafter referred to as heme peroxidase 1 (HPx1). HPx1 promotes PM assembly and antioxidant ability, modulating vector competence. Mechanistically, the heme presence in a blood meal induces HPx1 transcriptional activation mediated by the E75 transcription factor. HPx1 knockdown increases midgut reactive oxygen species (ROS) production by the DUOX NADPH oxidase. Elevated ROS levels reduce microbiota growth while enhancing epithelial mitosis, a response to tissue damage. However, simultaneous HPx1 and DUOX silencing was not able to rescue bacterial population growth, as explained by increased expression of antimicrobial peptides (AMPs), which occurred only after double knockdown. This result revealed hierarchical activation of ROS and AMPs to control microbiota. HPx1 knockdown produced a 100-fold decrease in Zika and Dengue 2 midgut infection, demonstrating the essential role of the mosquito PM in the modulation of arbovirus vector competence. Our data show that the PM connects blood digestion to midgut immunological sensing of the microbiota and viral infections.
PPP2R1A Regulates Migration Persistence through the WAVE Shell Complex
Authors: Wang Yanan , Chiappetta Giovanni , Guérois Raphaël , Romero Stéphane , Krause Matthias , Dessalles Claire , Babataheri Avin , Barakat Abdul I. , Vinh Joelle , Polesskaya Anna , Gautreau Alexis M. 
Published: June 2022

AbstractThe RAC1-WAVE-Arp2/3 signaling pathway generates branched actin networks that power lamellipodium protrusion of migrating cells. Feedback is thought to control protrusion lifetime and migration persistence, but its molecular circuitry remains elusive. Using proteomics, we identified PPP2R1A among proteins differentially associated with the WAVE complex subunit ABI1 when RAC1 was activated and downstream generation of branched actin was blocked. PPP2R1A was found to associate at the lamellipodial edge with a novel form of WAVE complex, the WAVE Shell Complex (WSC), that contains NHSL1 instead of the Arp2/3 activating subunit WAVE as in the canonical WAVE Regulatory Complex (WRC). PPP2R1A was required for persistence in random and directed migration assays and for RAC1-dependent actin polymerization in cell extracts. PPP2R1A requirement was abolished by NHSL1 depletion. PPP2R1A mutations found in tumors impaired WSC binding and migration regulation, suggesting that this novel function of PPP2R1A is critical for its tumor suppressor activity.
The extracellular RNA pool within Zea mays apoplast: composition and differential expression during Ustilago maydis infection
Authors: Mukherjee Dibya , Singh Nagendra Pratap , Roy Anisha , Mondal Rituparna , Acharya Udita , Chattopadhyay Debasis , Ghosh Anupama 
Published: June 2022

AbstractThe existence of an extracellular pool of RNA (exRNA) has been documented in both animal and plant cells in a number of instances. These exRNA species play important role in host response against different environmental stimuli. The mechanism of their function however remains largely unknown. In this study we report the composition of the exRNA pool within the leaf apoplast of Z. mays under normal growth condition. We could detect RNA transcripts originating from both the genic as well as the intergenic regions of the nuclear, mitochondrial and chloroplast genomes of maize in our exRNA sequencing data. Our data showed increased abundance of about 75% of the exRNA transcripts during infection with a basidiomycete smut fungi, Ustilago maydis. Functional classification of the differentially abundant exRNA transcripts within U. maydis SG200 WT infected maize apoplast with respect to uninfected apoplast revealed significant enrichment of the exRNA transcripts corresponding to the ribosome biogenesis pathway. Data related to the effect of two extracellular T2 type ribonucleases, Nuc1 and Nuc2 from U. maydis on the composition of exRNA pool of maize is also presented.
Robust deep learning based protein sequence design using ProteinMPNN
Authors: Dauparas J. , Anishchenko I. , Bennett N. , Bai H. , Ragotte R. J. , Milles L. F. , Wicky B. I. M. , Courbet A. , de Haas R. J. , Bethel N. , Leung P. J. Y. , Huddy T. F. , Pellock S. , Tischer D. , Chan F. , Koepnick B. , Nguyen H. , Kang A. , Sankaran B. , Bera A. K. , King N. P. , Baker D. 
Published: June 2022

AbstractWhile deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo protein designs have been generated using physically based approaches such as Rosetta. Here we describe a deep learning based protein sequence design method, ProteinMPNN, with outstanding performance in both in silico and experimental tests. The amino acid sequence at different positions can be coupled between single or multiple chains, enabling application to a wide range of current protein design challenges. On native protein backbones, ProteinMPNN has a sequence recovery of 52.4%, compared to 32.9% for Rosetta. Incorporation of noise during training improves sequence recovery on protein structure models, and produces sequences which more robustly encode their structures as assessed using structure prediction algorithms. We demonstrate the broad utility and high accuracy of ProteinMPNN using X-ray crystallography, cryoEM and functional studies by rescuing previously failed designs, made using Rosetta or AlphaFold, of protein monomers, cyclic homo-oligomers, tetrahedral nanoparticles, and target binding proteins.One-sentence summaryA deep learning based protein sequence design method is described that is widely applicable to current design challenges and shows outstanding performance in both in silico and experimental tests.
Selection on plastic adherence leads to hyper-multicellular strains and incidental virulence in the budding yeast
Authors: Ekdahl Luke I. , Salcedo Juliana A. , Dungan Matthew M. , Mason Despina V. , Myagmarsuren Dulguun , Murphy Helen A. 
Published: June 2022

SummaryMany disease-causing microbes are not obligate pathogens; rather, they are environmental microbes taking advantage of an ecological opportunity. The existence of microbes that are not normally pathogenic, yet are well-suited to host exploitation, is an evolutionary paradox. One hypothesis posits that selection in the environment may favor traits that incidentally lead to pathogenicity and virulence, or serve as pre-adaptations for survival in a host. An example of such a trait is surface adherence. To experimentally test the idea of “accidental virulence”, replicate populations of the yeast, Saccharomyces cerevisiae, which can be an opportunistic pathogen, were evolved to attach to a plastic bead for hundreds of generations. Along with plastic adherence, two multicellular phenotypes— biofilm formation and flor formation— increased; another phenotype, pseudohyphal growth, responded to the nutrient limitation. Thus, experimental selection led to the evolution of highly-adherent, hyper-multicellular strains. Wax moth larvae injected with evolved hyper-multicellular strains were significantly more likely to die than those injected with evolved non-multicellular strains. Hence, selection on plastic adherence incidentally led to the evolution of enhanced multicellularity and increased virulence. Our results support the idea that selection in the environment for a trait unrelated to virulence can inadvertently generate opportunistic, “accidental” pathogens.
Wetting and complex remodeling of membranes by biomolecular condensates
Authors: Mangiarotti Agustín , Chen Nannan , Zhao Ziliang , Lipowsky Reinhard , Dimova Rumiana 
Published: June 2022

AbstractCells compartmentalize their components in liquid-like condensates, which can be reconstitutedin vitro. Although these condensates interact with membrane-bound organelles, the potential of membrane remodeling and the underlying mechanisms are not well understood. Here, we demonstrate that interactions between protein condensates (including hollow ones) and membranes can lead to remarkable morphological transformations and describe these with theory. Modulation of solution salinity or membrane composition drives the condensate-membrane system through two wetting transitions, from dewetting, through a broad regime of partial wetting, to complete wetting. A new phenomenon, namely fingering or ruffling of the condensate-membrane interface is observed when sufficient membrane area is available, producing intricately curved structures. The observed morphologies are governed by the interplay of adhesion, membrane elasticity, and interfacial tension. Our results highlight the relevance of wetting in cell biology, and pave the way for the design of synthetic membrane-droplet based biomaterials and compartments with tunable properties.
Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss
Authors: Larouche Jacqueline A. , Wallace Emily C. , Spence Bonnie D. , Johnson Scott A. , Kulkarni Mangesh , Buras Eric , Brown Bryan N. , Badylak Stephen F. , Aguilar Carlos A. 
Published: June 2022

ABSTRACTVolumetric muscle loss (VML) is an acute trauma that results in persistent inflammation, supplantation of muscle tissue with fibrotic scarring, and decreased muscle function. The cell types, nature of cellular communication and tissue locations that drive the aberrant VML response have remained elusive. Herein, we used spatial transcriptomics integrated with single-cell RNA sequencing on mouse and canine models administered VML. We observed VML engenders a unique spatial pro-fibrotic pattern driven by crosstalk between macrophages and fibro-adipogenic progenitors that was conserved between murine and canine models albeit with varying kinetics. This program was observed to restrict muscle stem cell mediated repair and targeting this circuit in a murine model resulted in increased regeneration and reductions in inflammation and fibrosis. Collectively, these results enhance our understanding of the immune cell-progenitor cell-stem cell crosstalk that drives regenerative dysfunction and provides further insight into possible avenues for fibrotic therapy exploration.
NOS2 and COX2 Blockade Limits TNBC Disease Progression and Alters CD8+T Cell Spatial Orientation and Density
Authors: Somasundaram Veena , Ridnour Lisa A , Cheng Robert YS , Walke Abigail J , Kedei Noemi , Bhattacharyya Dibyangana D , Wink Adelaide L , Edmondson Elijah F , Butcher Donna , Warner Andrew , Dorsey Tiffany H , Scheiblin David A , Heinz William , Bryant Richard J. , Kinders Robert , Lipkowitz Stanley , Wong Stephen TC , Pore Milind , Hewitt Stephen M. , McVicar Daniel W , Anderson Stephen K , Chang Jenny , Glynn Sharon A , Ambs Stefan , Lockett Stephen J. , Wink David A 
Published: June 2022

AbstractAnti-tumor immune polarization is a key predictor of clinical outcomes to cancer therapy. An emerging concept influencing clinical outcome involves the spatial location of CD8+T cells, within the tumor. Our earlier work demonstrated immunosuppressive effects of NOS2/ COX2 tumor expression. Here, we show that NOS2/COX2 levels influence the polarization and spatial location of lymphoid cells including CD8+T cells. Importantly, elevated tumor NOS2/COX2 correlated with exclusion of CD8+T cells from the tumor epithelium. In contrast, tumors expressing low NOS2/COX2 had increased CD8+T cell penetration into the tumor epithelium. Consistent with a causative relationship between these observations, pharmacological inhibition of COX2 with indomethacin dramatically reduced tumor growth of the 4T1 model of TNBC in bothWTandNos2-/-mice. This regimen led to complete tumor regression in ∼20% of tumor-bearingNos2-/-mice, and these animals were resistant to tumor rechallenge. Th1 cytokines were elevated in the blood of treated mice and intratumoral CD4+and CD8+T cells were higher in mice that received indomethacin when compared to control untreated mice. Multiplex immunofluorescence imaging confirmed our phenotyping results and demonstrated that targeted Nos2/Cox2 blockade improved CD8+T cell penetration into the 4T1 tumor core. These findings are consistent with our observations in low NOS2/COX2 expressing breast tumors` proving that COX2 activity is responsible for limiting the spatial distribution of effector T cells in TNBC. Together these results suggest that clinically available NSAID’s may provide a cost-effective, novel immunotherapeutic approach for treatment of aggressive tumors including triple negative breast cancer.
Protein nanobarcodes enable single-step multiplexed fluorescence imaging
Authors: de Jong-Bolm Daniëlle , Sadeghi Mohsen , Bao Guobin , Klaehn Gabriele , Hoff Merle , Mittelmeier Lucas , Basmanav F. Buket , Opazo Felipe , Noé Frank , Rizzoli Silvio O. 
Published: June 2022

AbstractMultiplexed cellular imaging typically relies on the sequential application of detection probes, such as antibodies or DNA barcodes, which is complex and time-consuming. To address this, we developed here protein nanobarcodes, composed of combinations of epitopes recognized by specific sets of nanobodies. The nanobarcodes are read in a single imaging step, relying on nanobodies conjugated to distinct fluorophores, which enables a precise analysis of large numbers of protein combinations.