bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding continuous kinetic information of grasp from stereo-electroencephalographic (SEEG) recordings
Authors: Wu Xiaolong , Li Guangye , Jiang Shize , Wellington Scott , Liu Shengjie , Wu Zehan , Metcalfe Benjamin , Chen Liang , Zhang Dingguo
Published: April 2022

Objective. Brain–computer interfaces (BCIs) have the potential to bypass damaged neural pathways and restore functionality lost due to injury or disease. Approaches to decoding kinematic information are well documented; however, the decoding of kinetic information has received less attention. Additionally, the possibility of using stereo-electroencephalography (SEEG) for kinetic decoding during hand grasping tasks is still largely unknown. Thus, the objective of this paper is to demonstrate kinetic parameter decoding using SEEG in patients performing a grasping task with two different force levels under two different ascending rates. Approach. Temporal-spectral representations were studied to investigate frequency modulation under different force tasks. Then, force amplitude was decoded from SEEG recordings using multiple decoders, including a linear model, a partial least squares model, an unscented Kalman filter, and three deep learning models (shallow convolutional neural network, deep convolutional neural network and the proposed CNN+RNN neural network). Main results. The current study showed that: (a) for some channel, both low-frequency modulation (event-related desynchronization (ERD)) and high-frequency modulation (event-related synchronization) were sustained during prolonged force holding periods; (b) continuously changing grasp force can be decoded from the SEEG signals; (c) the novel CNN+RNN deep learning model achieved the best decoding performance, with the predicted force magnitude closely aligned to the ground truth under different force amplitudes and changing rates. Significance. This work verified the possibility of decoding continuously changing grasp force using SEEG recordings. The result presented in this study demonstrated the potential of SEEG recordings for future BCI application.
Growth and characterization of uniformly distributed triangular single-crystalline hexagonal boron nitride grains on liquid copper surface
Authors: Hao Ziqiang , Liu Xuechao , Zhu Xinfeng , Zhang Minghui , Tang Meibo , Pan Xiuhong
Published: April 2022

Single-layer hexagonal boron nitride (h-BN) is a two-dimensional (2D) material with a wide band gap and extraordinary mechanical, thermal and optical properties. It has promising applications in optoelectronics, electronics and photovoltaics. Low-pressure (150 Pa) chemical vapor deposition (LPCVD) was used to prepare uniformly distributed single-crystalline triangular h-BN grains and continuous film on liquid copper surface. A series of microscopic and spectroscopic methods were performed to characterize the morphology, crystalline structure and quality, component and thickness. It was found that h-BN grains turned into circles at higher background pressure (1000 Pa), which was due to the change in the growth mechanism from equilibrium controlled to deposition controlled. Small islands formed on primary h-BN grains because of higher concentration of precursor product. Compared to the higher background pressure, the synthetic h-BN films at low background pressure exhibited larger domain size, lower nucleation density, and no adlayer growth. Due to randomly distributed polar h-BN grains, the grain boundaries formed along the h-BN domains after merging. Typical patterns formed via the coalescence of triangular h-BN grains indicating the merging mode of growth, including edge-to-edge and edge-to-point modes. This work provides a pathway for the preparation of uniformly distributed single-crystalline h-BN grains and an in-depth understanding of the growth and merging process on liquid Cu surface.
Feedback-enabled microwave quantum illumination
Authors: Ebrahimi Mehri Sadat , Zippilli Stefano , Vitali David
Published: April 2022

A simple feedback scheme can be used to operate efficiently a microwave-quantum-illumination device based on electro-optomechanical systems also in regimes in which excess dissipation would, otherwise, prevent to outperform the optimal classical illumination protocol with the same transmitted energy.
Mechanical, electrochemical and multifunctional performance of a CFRP/carbon aerogel structural supercapacitor and its corresponding monofunctional equivalents
Authors: Pernice Maria Francesca , Qi Guocheng , Senokos Evgeny , Anthony David B , Nguyen Sang , Valkova Maria , Greenhalgh Emile S , Shaffer Milo S P , Kucernak Anthony R J
Published: April 2022

This work investigated and developed a protocol for establishing the multifunctional performance of a structural supercapacitor: a composite which can simultaneously carry mechanical load whilst storing electrical energy. The Structural Supercapacitor consisted of carbon aerogel (CAG) reinforced carbon fibre electrodes which sandwiched a woven glass fibre lamina and was infused with a structural electrolyte (SE). This was compared to two monofunctional devices: a Monofunctional Supercapacitor and a Monofunctional Laminate in which the SE had been replaced by ionic liquid and a structural epoxy, respectively. In the Monofunctional Supercapacitor, the considerable surface area of the CAG and ionic capacity of the liquid electrolyte resulted in a high device normalised capacitance (1731 mF g−1). However, in the Structural Supercapacitor the SE presented meso-scale heterogeneity, obstructing the CAG pores with thin films of epoxy. This resulted in a considerable reduction in electrochemical performance, with a drop in the device normalised capacitance to 212 mF g−1. Regarding mechanical performance, it was shown that the CAG had promoted brittle fracture, leading to a severe depression in the tensile and in-plane shear strengths. The Structural Supercapacitor presented a tensile modulus and strength of 33 GPa and 110 MPa, respectively: a 15% and 11% drop in tensile modulus and strength, respectively, compared to that of the Monofunctional Laminate. However, under in-plane shear the soft SE dominated, leading to about a 44% drop in shear modulus (1.7 GPa) and strength (13.7 MPa at 1% shear strain). This work has provided an insight into the hurdles associated with demonstrating multifunctionality, including the scaling challenges for electrochemical and mechanical characterisation and the need to report both active material and device normalised data. The emergence and development of such structural power composites could address the issue of parasitic battery mass in transportation, and hence realise full electrification of aircraft and cars.
Enhanced charge transport of conjugated polymer/reduced graphene oxide composite films by solvent vapor pre-treatment
Authors: Proscovia Kyokunzire , Cheon Hyeong Jun , Shin Seo Young , Jeong Ganghoon , Go Seongmoon , Kim Keun Seong , Park Rae-Su , Huh Yang-Il , Chang Mincheol
Published: April 2022

In this study, a facile approach that could provide a significant enhancement of the charge transport properties of the conjugated polymer/reduced graphene oxide (rGO) composite films using a non-solvent vapor treatment is reported. As the methanol vapors were exposed to the poly(3-hexylthiophene) (P3HT)/rGO composite solution, P3HT chains self-assembled to create nanofibrillar structures via favorable π–π interactions. The π–π staking in P3HT occurred by the non-solvent vapor exposure to minimize unfavorable interactions of P3HT chains with the non-solvent vapor molecules. The self-assembly of P3HT chains was chiefly facilitated by the presence of rGO. This is because the surface of rGO can serve as nucleation sites for the growth of P3HT nanowires. Consequently, P3HT/rGO composite films obtained from the methanol vapor treated corresponding solutions exhibited a high charge carrier mobility (1.3 × 10−1 cm2 V−1 s−1), which is approximately 11-times and 6.5-times higher than those of pristine P3HT (1.2 × 10−2 cm2 V−1 s−1) and P3HT/rGO (2.0 × 10−2 cm2 V−1 s−1) composite films, respectively.
Emerging insights into synapse dysregulation in Alzheimer’s disease
Authors: Martínez-Serra Raquel , Alonso-Nanclares Lidia , Cho Kwangwook , Giese K. Peter
Published: April 2022

Alzheimer’s disease is the leading cause of dementia and a growing worldwide problem, with its incidence expected to increase in the coming years. Since synapse loss is a major pathology and is correlated with symptoms in Alzheimer’s disease, synapse dysfunction and loss may underlie pathophysiology. In this context, this review focuses on emerging insights into synaptic changes at the ultrastructural level. The three-dimensional electron microscopy technique unequivocally detects all types of synapses, including multi-synapses, which are indicators of synaptic connectivity between neurons. In recent years it has become feasible to perform sophisticated three-dimensional electron microscopy analyses on post-mortem human Alzheimer’s disease brain as tissue preservation and electron microscopy techniques have improved. This ultrastructural analysis found that synapse loss does not always precede neuronal loss, as long believed. For instance, in the transentorhinal cortex and area CA1 of the hippocampus, synapse loss does not precede neuronal loss. However, in the entorhinal cortex, synapse loss precedes neuronal loss. Moreover, the ultrastructural analysis provides details about synapse morphology. For example, changes in excitatory synapses’ post-synaptic densities, with fragmented postsynaptic densities increasing at the expense of perforated synapses, are seen in Alzheimer’s disease brain. Further, multi-synapses also appear to be altered in Alzheimer’s disease by doubling the abundance of multi-innervated spines in the transentorhinal cortex of Alzheimer’s disease brain. Collectively, these recent ultrastructural analyses highlight distinct synaptic phenotypes in different Alzheimer’s disease brain regions and broaden the understanding of synapse alterations, which may unravel some new therapeutic targets.
Patterns of genomic divergence in sympatric and allopatric speciation of three Mihoutao (Actinidia) species
Authors: Liu Yongbo , Yu Wenhao , Wu Baofeng , Li Junsheng
Published: April 2022

Isolation by geographic distance is involved in the formation of potential genomic islands and the divergence of genomes, which often result in speciation. The mechanisms of sympatric and allopatric speciation associated with geographic distance remain a topic of interest to evolutionary biologists. Here, we examined genomic divergence in three Actinidia species from large-scale sympatric and allopatric regions. Genome sequence data revealed that hexaploid Actinidia deliciosa originated from Actinidia chinensis and supported the speciation-with-gene-flow model in sympatric regions. The common ancestor of Actinidia setosa and A. deliciosa migrated from the mainland to the Taiwan Island ~2.91 Mya and formed A. setosa ~0.92 Mya, and the speciation of A. setosa is consistent with the divergence-after-speciation model with selective sweeps. Geographic isolation resulted in population contraction and accelerated the process of lineage sorting and speciation due to natural selection. Genomic islands contained genes associated with organ development, local adaptation, and stress resistance, indicating selective sweeps on a specific set of traits. Our results highlight the patterns of genomic divergence in sympatric and allopatric speciation, with the mediation of geographic isolation in the formation of genomic islands during Actinidia speciation.
Patients With Inflammatory Bowel Diseases Have Impaired Antibody Production After Anti-SARS-CoV-2 Vaccination: Results From a Panhellenic Registry
Authors: Zacharopoulou Eirini , Orfanoudaki Eleni , Tzouvala Maria , Tribonias George , Kokkotis Georgios , Kitsou Vassiliki , Almpani Foteini , Christidou Aggeliki , Viazis Nikolaos , Mantzaris Gerassimos J , Tsafaridou Maria , Karmiris Konstantinos , Theodoropoulou Angeliki , Papathanasiou Evgenia , Zampeli Evanthia , Michopoulos Spyridon , Tigkas Stefanos , Michalopoulos Georgios , Laoudi Efrossini , Karatzas Pantelis , Mylonas Iordanis , Kyriakos Nikolaos , Liatsos Christos , Kafetzi Theodora , Theocharis Georgios , Taka Styliani , Panagiotopoulou Konstantina , Koutroubakis Ioannis E , Bamias Giorgos
Published: April 2022

Background

Four EMA-approved vaccines against SARS-CoV-2 are currently available. Data regarding antibody responses to initial vaccination regimens in patients with inflammatory bowel diseases (IBD) are limited.

Methods

We conducted a prospective, controlled, multicenter study in tertiary Greek IBD centers. Participating patients had completed the initial vaccination regimens (1 or 2 doses, depending on the type of COVID-19 vaccine) at least 2 weeks before study enrolment. Anti-S1 IgG antibody levels were measured. Demographic and adverse events data were collected.

Results

We tested 403 patients (Crohn’s disease, 58.9%; male, 53.4%; median age, 45 years) and 124 healthy controls (HCs). Following full vaccination, 98% of patients seroconverted, with mRNA vaccines inducing higher seroconversion rates than viral vector vaccines (P = .021). In total, IBD patients had lower anti-S1 levels than HCs (P < .001). In the multivariate analysis, viral vector vaccines (P < .001), longer time to antibody testing (P < .001), anti-TNFα treatment (P = .013), and age (P = .016) were independently associated with lower anti-S1 titers. Vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or anti-interleukin-12/IL-23 monotherapy (P = .023 and P = .032). All anti- SARS-CoV-2 vaccines were safe.

Conclusions

Patients with IBD have impaired antibody responses to anti-SARS-CoV-2 vaccination, particularly those receiving viral vector vaccines and those on anti-TNFα treatment. Older age also hampers antibody production after vaccination. For those low-response groups, administration of accelerated or prioritized booster vaccination may be considered.
Real-world 6-month outcomes of minimally invasive aortic valve replacement with the EDWARDS INTUITY Elite valve system
Authors: Laufer Günther , Strauch Justus T , Terp Kim A , Salinas Marco , Arribas Jose M , Massetti Massimo , Andreas Martin , Young Christopher P
Published: April 2022

OBJECTIVES

We report on real-world safety and performance outcomes of minimally invasive rapid-deployment aortic valve replacement using the EDWARDS INTUITY Elite aortic valve system.

METHODS

The study valve system was used in a European, prospective, multicentre post-market study. Various procedural, haemodynamic and clinical outcomes were evaluated through 6 months of post-implant.

RESULTS

A total of 276 patients out of 280 (98.6%) enrolments were successfully implanted with the study valve using a minimally invasive approach between February 2016 and April 2017. Of these 276 patients, 240 (87%) underwent partial sternotomy and 36 (13%) patients underwent right thoracotomy. Mean cross-clamp time was 51.9 [standard deviation (SD): 16.0] min. From baseline to 6 months, the mean effective orifice area increased from 0.8 (SD: 0.3) to 1.8 (SD: 0.6) cm2 and the mean systolic gradient decreased from 46.0 (SD: 14.1) to 8.8 (SD: 3.7) mmHg. After 6 months, 70.7% and 26.4% of patients were in New York Heart Association class I and II, respectively. Freedom from death, major bleeding, major paravalvular leak, reoperation and device explant at 6 months were 96.0%, 98.5%, 98.8%, 99.2% and 99.2%, respectively.

CONCLUSIONS

These results demonstrate that the study valve is a safe and effective choice for patients undergoing aortic valve replacement via minimally invasive surgery.

Name and registration of registry

MISSION (Assessing clinical outcomes using the EDWARDS INTUITY Elite Valve System in isolated AVR using Minimally InvaSive Surgery In a EurOpean multi-ceNter, active, post-market registry). clinicaltrials.gov ID #NCT02907463.
Generalized Stochastic Areas, Winding Numbers, and Hyperbolic Stiefel Fibrations
Authors: Baudoin Fabrice , Demni Nizar , Wang Jing
Published: April 2022

We study the Brownian motion on the non-compact Grassmann manifold $\frac {\textbf {U}(n-k,k)} {\textbf {U}(n-k)\textbf {U}(k)}$ and some of its functionals. The key point is to realize this Brownian motion as a matrix diffusion process, use matrix stochastic calculus and take advantage of the hyperbolic Stiefel fibration to study a functional that can be understood in that setting as a generalized stochastic area process. In particular, a connection to the generalized Maass Laplacian of the complex hyperbolic space is presented and applications to the study of Brownian windings in the Lie group $\textbf {U}(n-k,k)$ are then given.
Interests, Institutions, and the Environment: An Examination of Fisheries Subsidies
Authors: Rickard Stephanie J
Published: April 2022

Protecting the environment has emerged as one of the major challenges in international relations. In international environmental negotiations, countries hold divergent positions because of domestic politics and specifically the interaction of interests and institutions. Domestic political institutions privilege the interests of some groups over others, depending on their geographic distribution. This observation matters for global environmental cooperation because groups with varied interests in protecting the environment often exhibit different geographic patterns, as illustrated in negotiations over fisheries subsidies at the World Trade Organization (WTO). The fishing industry tends to be concentrated in geographic space because of its reliance on a geographically specific natural resource. The industry’s geographic concentration gives it relatively more political clout in countries with plurality electoral systems. Environmentalists, who tend to be more diffuse geographically, enjoy greater political influence in countries with proportional representation systems and party-centered electoral competition. These political dynamics, as well as the electoral success of Green political parties, influence governments’ spending priorities as well as states’ positions in international environmental negotiations.
Structural basis for the linkage specificity of ubiquitin-binding domain and deubiquitinase
Authors: Sato Yusuke
Published: April 2022

Ubiquitination is a post-translational modification system essential for regulating a wide variety of biological processes in eukaryotes. Ubiquitin (Ub) itself undergoes post-translational modifications, including ubiquitination. All seven lysine residues and one N-terminal amino group of Ub can act as acceptors for further ubiquitination, producing eight types of Ub chains. Ub chains of different linkage types have different cellular functions and are referred to as the ‘ubiquitin code’. Decoder molecules that contain linkage-specific Ub-binding domains (UBDs) recognize the Ub chains to regulate different cellular functions. On the other hand, deubiquitinases (DUBs) cleave Ub chains to reverse ubiquitin signals. This review discusses the molecular mechanisms of linkage-specific recognitions of Ub chains by UBDs and DUBs, which have been revealed by structural studies.
CRISPR/Cas9 gene editing uncovers the roles of CONSTITUTIVE TRIPLE RESPONSE 1 and REPRESSOR OF SILENCING 1 in melon fruit ripening and epigenetic regulation
Authors: Giordano Andrea , Santo Domingo Miguel , Quadrana Leandro , Pujol Marta , Martín-Hernández Ana Montserrat , Garcia-Mas Jordi
Published: April 2022

Melon (Cucumis melo) has emerged as an alternative model to tomato for studying fruit ripening due to the coexistence of climacteric and non-climacteric varieties. Previous characterization of a major quantitative trait locus (QTL), ETHQV8.1, that is able to trigger climacteric ripening in a non-climacteric background resulted in the identification of a negative regulator of ripening CTR1-like (MELO3C024518) and a putative DNA demethylase ROS1 (MELO3C024516) that is the orthologue of DML2, a DNA demethylase that regulates fruit ripening in tomato. To understand the role of these genes in climacteric ripening, in this study we generated homozygous CRISPR knockout mutants of CTR1-like and ROS1 in a climacteric genetic background. The climacteric behavior was altered in both loss-of-function mutants in two growing seasons with an earlier ethylene production profile being observed compared to the climacteric wild type, suggesting a role of both genes in climacteric ripening in melon. Single-cytosine methylome analyses of the ROS1-knockout mutant revealed changes in DNA methylation in the promoter regions of the key ripening genes such as ACS1, ETR1, and ACO1, and in transcription factors associated with ripening including NAC-NOR, RIN, and CNR, suggesting the importance of ROS1-mediated DNA demethylation for triggering fruit ripening in melon.
Major niche transitions in Pooideae correlate with variation in photoperiodic flowering and evolution of CCT domain genes
Authors: Fjellheim Siri , Young Darshan A , Paliocha Martin , Johnsen Sylvia Sagen , Schubert Marian , Preston Jill C
Published: April 2022

The external cues that trigger timely flowering vary greatly across tropical and temperate plant taxa, the latter relying on predictable seasonal fluctuations in temperature and photoperiod. In the grass family (Poaceae) for example, species of the subfamily Pooideae have become specialists of the northern temperate hemisphere, generating the hypothesis that their progenitor evolved a flowering response to long days from a short-day or day-neutral ancestor. Sampling across the Pooideae, we found support for this hypothesis, and identified several secondary shifts to day-neutral flowering and one to short-day flowering in a tropical highland clade. To explain the proximate mechanisms for the secondary transition back to short-day-regulated flowering, we investigated the expression of CCT domain genes, some of which are known to repress flowering in cereal grasses under specific photoperiods. We found a shift in CONSTANS 1 and CONSTANS 9 expression that coincides with the derived short-day photoperiodism of our exemplar species Nassella pubiflora. This sets up the testable hypothesis that trans- or cis-regulatory elements of these CCT domain genes were the targets of selection for major niche shifts in Pooideae grasses.
Multi-omics data integration analysis identifies the spliceosome as a key regulator of DNA double-strand break repair
Authors: Sherill-Rofe Dana , Raban Oded , Findlay Steven , Rahat Dolev , Unterman Irene , Samiei Arash , Yasmeen Amber , Kaiser Zafir , Kuasne Hellen , Park Morag , Foulkes William D , Bloch Idit , Zick Aviad , Gotlieb Walter H , Tabach Yuval , Orthwein Alexandre
Published: April 2022

DNA repair by homologous recombination (HR) is critical for the maintenance of genome stability. Germline and somatic mutations in HR genes have been associated with an increased risk of developing breast (BC) and ovarian cancers (OvC). However, the extent of factors and pathways that are functionally linked to HR with clinical relevance for BC and OvC remains unclear. To gain a broader understanding of this pathway, we used multi-omics datasets coupled with machine learning to identify genes that are associated with HR and to predict their sub-function. Specifically, we integrated our phylogenetic-based co-evolution approach (CladePP) with 23 distinct genetic and proteomic screens that monitored, directly or indirectly, DNA repair by HR. This omics data integration analysis yielded a new database (HRbase) that contains a list of 464 predictions, including 76 gold standard HR genes. Interestingly, the spliceosome machinery emerged as one major pathway with significant cross-platform interactions with the HR pathway. We functionally validated 6 spliceosome factors, including the RNA helicase SNRNP200 and its co-factor SNW1. Importantly, their RNA expression correlated with BC/OvC patient outcome. Altogether, we identified novel clinically relevant DNA repair factors and delineated their specific sub-function by machine learning. Our results, supported by evolutionary and multi-omics analyses, suggest that the spliceosome machinery plays an important role during the repair of DNA double-strand breaks (DSBs).
Prospective genomically guided identification of “early/evolving” and “undersampled” IDH-wildtype glioblastoma leads to improved clinical outcomes
Authors: Zhang Yalan , Lucas Calixto-Hope G , Young Jacob S , Morshed Ramin A , McCoy Lucie , Oberheim Bush Nancy Ann , Taylor Jennie W , Daras Mariza , Butowski Nicholas A , Villanueva-Meyer Javier E , Cha Soonmee , Wrensch Margaret , Wiencke John K , Lee Julieann C , Pekmezci Melike , Phillips Joanna J , Perry Arie , Bollen Andrew W , Aghi Manish K , Theodosopoulos Philip , Chang Edward F , Hervey-Jumper Shawn L , Berger Mitchel S , Clarke Jennifer L , Chang Susan M , Molinaro Annette M , Solomon David A
Published: April 2022

Background

Genomic profiling studies of diffuse gliomas have led to new improved classification schemes that better predict patient outcomes compared to conventional histomorphology alone. One example is the recognition that patients with IDH-wildtype diffuse astrocytic gliomas demonstrating lower-grade histologic features but genomic and/or epigenomic profile characteristic of glioblastoma typically have poor outcomes similar to patients with histologically diagnosed glioblastoma. Here we sought to determine the clinical impact of prospective genomic profiling for these IDH-wildtype diffuse astrocytic gliomas lacking high-grade histologic features but with molecular profile of glioblastoma.

Methods

Clinical management and outcomes were analyzed for 38 consecutive adult patients with IDH-wildtype diffuse astrocytic gliomas lacking necrosis or microvascular proliferation on histologic examination that were genomically profiled on a prospective clinical basis revealing criteria for an integrated diagnosis of “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV” per cIMPACT-NOW criteria.

Results

We identified that this diagnosis consists of two divergent clinical scenarios based on integration of radiologic, histologic, and genomic features that we term “early/evolving” and “undersampled” glioblastoma, IDH-wildtype. We found that prospective genomically guided identification of early/evolving and undersampled IDH-wildtype glioblastoma resulted in more aggressive patient management and improved clinical outcomes compared to a biologically matched historical control patient cohort receiving standard-of-care therapy based on histomorphologic diagnosis alone.

Conclusions

These results support routine use of genomic and/or epigenomic profiling to accurately classify glial neoplasms, as these assays not only improve diagnostic classification but critically lead to more appropriate patient management that can improve clinical outcomes.
Silent Persistent Left Superior Vena Cava Right-to-Left Shunt as a Unique Cause of Recurrent Brain Abscesses
Authors: Spier Addie B , David Diana , Al Zoubi Moamen , Taylor Montoya , Evans Colin E
Published: April 2022

We present a novel case of recurrent brain abscesses found to be the result of a silent congenital right-to-left extracardiac shunt, a persistent left superior vena cava draining into the left atrium. The patient’s brain abscess was evacuated surgically and treated with antibiotics, and his shunt was subsequently repaired. The case suggests that attention should be paid to evaluation for shunt physiology allowing for bypass of the pulmonary circulation in those with recurrent brain abscesses.
Original Research: Combating the Opioid Epidemic Through Nurse Use of Multimodal Analgesia: An Integrative Literature Review
Authors: Tavernier Jennifer René
Published: April 2022

Background:

Opioid misuse and addiction have become a national crisis. New pain management guidelines call for the use of multimodal analgesia to manage acute pain. In hospital settings, a clinical decision aid that emphasizes multimodal analgesia may improve nurses' use of this opioid-sparing strategy.

Purpose:

This integrative review was conducted to provide nurses with evidence-based information on the opioid-sparing benefits of multimodal analgesia.

Methods:

A literature search was conducted using several electronic databases and Google Scholar. These initial searches yielded 136 articles of interest. Twenty-eight were selected for retrieval and in-depth appraisal; of these, 13 met all inclusion criteria.

Results:

Of the 13 reviewed studies, six were randomized controlled trials, six were retrospective cohort or population-based studies, and one was a qualitative study. Overall, the findings provided strong evidence that multimodal analgesia is effective in managing acute pain in surgical patients while reducing opioid requirements. Several studies also found that multimodal analgesia was associated with shorter hospital lengths of stay.

Conclusions:

With the appropriate tools and education, nurses can make the transition from traditional opioids to multimodal analgesia strategies. In so doing, they can have a significant positive impact on the opioid epidemic. Hospital leaders must address nursing practice regarding the use of opioids alone versus multimodal analgesia for the management of acute pain. Clinical decision tools such as the Michigan Opioid Safety Score may help nurses adopt new acute pain management guidelines. Further research regarding nursing practice and the opioid epidemic is needed.
Clinical Effects of Inadvertent Increased Lipid Infusion in Neonates
Authors: Hulgan Christina Marie , Snow Timothy , Check Jennifer
Published: April 2022

Background:

Utility of total parenteral nutrition (TPN) with an intravenous lipid emulsion (IVLE) component is common in the neonatal intensive care unit; however, there are inherent risks to TPN use. With IVLE administered separate from other TPN components, opportunities exist for additional error and subsequent potential harm.

Clinical Findings:

We present 2 cases in term infants where IVLE infusions were noted to be inadvertently administered at higher than prescribed rates, prompting concern for lipemia and end-organ damage due to hyperviscosity.

Primary Diagnosis:

Both infants developed iatrogenic hypertriglyceridemia and hyponatremia.

Intervention:

Upon recognition of the error, IVLE was immediately discontinued in each case. Triglyceride levels were serially monitored until they reached a normal level. Electrolyte panels and hepatic function panels were also drawn to assess for electrolyte derangements and function. Radiologic studies were performed for evaluation of end-organ effects of hyperviscosity.

Outcomes:

Triglyceride levels for both infants normalized within 7 hours. Both infants survived to discharge without any known effects related to the inadvertent excessive lipid infusion.

Conclusion:

It is helpful to perform a root-cause analysis for these types of events; have the exact amount of lipids in the bag needed and no overfill; consider having lipids in 4-hour dosage aliquots; require 2 nurses to verify infusion rates hourly; and educational sessions and unit protocols for any infusion may reduce the risk of administration error.
A Chitosan-Coated Chamomile Microparticles Formulation to Prevent Radiodermatitis in Breast
Authors: Garbuio Danielle C. , Ribeiro Vanessa dos Santos , Hamamura Ana C. , Faustino Alexandre , Freitas Luís Alexandre Pedro de , Viani Gustavo , Carvalho Emília Campos de
Published: April 2022

Purpose:

The aim was to evaluate the effect of a topical formulation containing chitosan-coated Chamomilla recutita (L.) rauschert microparticles regarding the incidence, grade, and days for the appearance of radiodermatitis (RD) in women with breast cancer.

Methods:

A double-blinded, controlled, randomized, phase II clinical trial developed with women diagnosed with breast cancer who will receive radiation therapy. The participants were randomly divided into 2 groups: control and treatment. They were followed up until the end of the treatment or the appearance of grade III RD.

Results:

Fifty-four women were included in the study. There is no significant difference between the groups in the incidence (88.9% vs. 88.9%, P=1.0) or time to develop any grade of RD (3 days of difference, P=0.300). A significant reduction was observed in the incidence (P=0.03) and in the time to appearance (7 d of difference, P=0.01) grade 2 or >RD. In the follow-up evaluation (15 d after the end of treatment), the Chamomile group presented a superior skin recovery than the control group (P=0.0343). High-intensity local symptoms as pain, and pruritus were significantly reduced in the Chamomile group.

Conclusions:

Although no effect was observed with chamomile to reduce any grade of RD, it was effective to reduce grade 2 or >toxicity, to improve skin recovery and to diminish high-intensity local symptoms.

Trial Registration:

Brazilian Registry of Clinical Trials (ReBEC): RBR-9hnftg, April 29, 2019.
Marginal Versus Conditional Odds Ratios When Updating Risk Prediction Models
Authors: Sadatsafavi Mohsen , Tavakoli Hamid , Safari Abdollah
Published: April 2022

Risk prediction models often need to be updated when applied to new settings. A simple updating method involves fixed odds ratio transformation of predicted risks to adjust the model for outcome prevalence in the new setting. When a sample from the target population is available, the gold standard is to use a logistic regression model to estimate this odds ratio. A simpler method has been proposed that calculates this odds ratio from the prevalence estimates in the original and new samples. We show that the marginal odds ratio estimated in this way is generally closer to one than the correct (conditional) odds ratio; thus, the simpler method should be avoided when individual-level data are available. When such data are not available, we suggest an approximate method for recovering the conditional odds ratio from the variance of predicted risks in the development sample. Brief simulations and examples show that this approach reduces undercorrection, often substantially.
High Tacrolimus Intrapatient Variability and Subtherapeutic Immunosuppression are Associated With Adverse Kidney Transplant Outcomes
Authors: Mendoza Rojas Aleixandra , Hesselink Dennis A. , van Besouw Nicole M. , Dieterich Marjolein , de Kuiper Ronella , Baan Carla C. , van Gelder Teun
Published: April 2022

Background:

Kidney transplant recipients with high intrapatient variability (IPV) in tacrolimus (Tac) exposure experience more rejection and reduced graft survival. To understand the underlying pathophysiology of this association, the authors investigated whether patients with high tacrolimus IPV have a more activated immune system than patients with low IPV. In addition, exposure to tacrolimus and mycophenolic acid (MPA) was studied in relation to rejection and graft survival.

Methods:

At the time of patient inclusion (5–7 years post-transplantation), the frequency of donor-reactive cells was determined by enzyme-linked immunosorbent assay, and the development of donor-specific anti-Human Leukocyte Antigen antibodies (DSA) was measured by Luminex Single Antigen assay. Tacrolimus IPV was retrospectively calculated between 6 and 12 months and the exposure to tacrolimus and MPA was determined between 1 and 5 years post-transplantation.

Results:

A total of 371 kidney transplant recipients were included in this study, of whom 56 developed a rejection episode after 12 months and 60 experienced graft failure after 5–7 years. No correlations were found between tacrolimus IPV or immunosuppression exposure and the number of donor-reactive cells after 5 years of transplantation. DSA were detected more often in patients with low exposure to both tacrolimus and MMF [4/21 (19%) versus 17/350 (4.9%), P = 0.04]. In this cohort, neither tacrolimus IPV nor low overall immunosuppression exposure was associated with a higher incidence of rejection. However, regression analysis showed that a higher tacrolimus IPV was associated with an increased incidence of graft failure (odds ratio = 1.03, P = 0.02).

Conclusions:

This study verifies the relationship between high tacrolimus IPV and impaired kidney allograft survival in long-term follow-up. DSA was also found to be more prevalent in patients with subtherapeutic concentrations of tacrolimus and MPA. An increased prevalence of donor-specific alloreactivity is yet to be demonstrated in patients with high IPV.
Accelerated Cranioplasty with Perforator-preserved Split Flap Sandwiched Plate for Treatment of Infected Cranial Defects
Authors: Okada Yoshimoto , Narushima Mitsunaga , Banda Chihena H. , Danno Kanako , Mitsui Kohei , Shiraishi Makoto , Shiba Masato , Suzuki Yume , Ishiura Ryohei
Published: April 2022

Large cranial vault defects are challenging to manage due to the need to balance infection control, skin coverage, and restoration of the protective mechanical rigidity of the skull while also ensuring good head and neck aesthetic results. Conventional-staged treatment requires a long time period that includes debridement and scalp skin defect coverage with flaps as a first step, followed by definitive plate reconstruction 3–9 months later after infection control and flap atrophy resolution. We report a case of successful early cranioplasty in a factory worker who developed a large full-thickness cranial skull defect following artificial dura infection. Reconstruction was performed in two stages using an anterolateral thigh (ALT) flap. In the first stage, the scalp defect was covered with an ALT flap to close the skin following debridement. In the second stage performed 6 weeks later, the ALT flap was split into adiposal and adipocutaneous flaps to sandwich a computer-aided design custom-made titanium plate with an opening for the perforator to complete the cranioplasty. The patient successfully returned to work without recurrence of infection with 1-year follow-up. We report this case to demonstrate the utility of adipocutaneous flap plate sandwiching techniques in providing well-vascularized cover for early definitive cranial reconstruction and accelerated patient recovery.
ASSOCIATED FACTORS AND SURGICAL OUTCOMES OF MICROCYSTOID MACULAR EDEMA AND CONE BOUQUET ABNORMALITIES IN EYES WITH EPIRETINAL MEMBRANE
Authors: Cicinelli Maria Vittoria , Post Michal , Brambati Maria , Rabiolo Alessandro , Pignatelli Francesco , Szaflik Jacek P. , Bandello Francesco , Coppola Michele
Published: April 2022

Purpose:

To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling.

Methods:

Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model.

Results:

One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3–12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97–0.99] for each 1-μm EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling (P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01–5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06–6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA.

Conclusion:

Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Müller cells may have an alleged role, and further imaging and functional tests are warranted.
Home-Based Perimetry for Glaucoma: Where Are We Now?
Authors: Daka Qëndresë , Mustafa Rona , Neziri Burim , Virgili Gianni , Azuara-Blanco Augusto
Published: April 2022

Purpose:

To systematically summarize the current literature on home-based perimeters for glaucoma.

Methods:

A systematic review was conducted in accordance with the PRISMA-DTA checklist. Studies reporting portable perimeters designed for home use were retrieved from electronic databases and handsearching of reference lists of relevant publications. Studies reporting diagnostic accuracy data were evaluated with the QUADAS-2 tool and using standard automated perimetry as the reference standard. Other aspects of the technology such as detection of disease progression and patient acceptability were also included. Data were reported in a narrative and tabular format.

Results:

Of 18 included studies, 10 evaluated tablet-based perimeters, 4 evaluated web-based perimeters, and 4 evaluated head-mounted displays. Most studies used a clinic or laboratory setting. All studies reporting diagnostic accuracy data had high risk of bias in at least one domain. Across studies, sensitivity ranged from 54% in detecting mild to 91% in detecting moderate/severe glaucoma patients from controls, while specificity was between 50% and 100% for any form of glaucoma. The reported acceptability was high but had high risk of bias.

Conclusion:

Several promising technologies designed for home-based perimetry have been reported. Current studies used a controlled setting in highly selected populations. There is uncertainty on the performance and value of home-based perimetry for glaucoma. Additional efforts are required to elucidate the ability of the home-based perimeters to detect glaucoma and disease progression in real life situations.
A Randomized, Controlled Comparison of NCX 470 (0.021%, 0.042%, and 0.065%) and Latanoprost 0.005% in Patients With Open-angle Glaucoma or Ocular Hypertension: The Dolomites Study
Authors: Walters Thomas R. , Kothe Angela C. , Boyer José L. , Usner Dale W. , Lopez Krisol , Duquesroix Brigitte , Fechtner Robert D. , Navratil Tomas
Published: April 2022

Précis:

NCX 470 0.042% and 0.065% were statistically superior in intraocular pressure (IOP) lowering to latanoprost 0.005%, and NCX 470 0.021% was noninferior. All NCX 470 concentrations were safe and well tolerated.

Purpose:

The purpose of this study was to compare varying concentrations of NCX 470 (a nitric oxide–donating bimatoprost) to latanoprost in a dose-response safety and efficacy trial.

Patients and Methods:

Adult patients with bilateral open-angle glaucoma or ocular hypertension were randomized to NCX 470 0.021% (n=111), 0.042% (n=108), 0.065% (n=107), or latanoprost 0.005% (n=107) once daily in the evening. IOP was measured at 8:00 am, 10:00 am, and 4:00 pm at weeks 1, 2, and 4. The primary efficacy endpoint was the reduction from baseline in mean diurnal IOP at week 4. Secondary efficacy endpoints included reductions from baseline in mean diurnal IOP at weeks 1 and 2, and reductions from baseline in time-matched IOP at 8:00 am, 10:00 am, and 4:00 pm at weeks 1, 2, and 4. Adverse events were evaluated.

Results:

All concentrations of NCX 470 resulted in significant reductions of mean diurnal IOP. The 0.042% and 0.065% concentrations were statistically superior to latanoprost 0.005%, and 0.021% was noninferior to latanoprost for change from baseline in mean diurnal IOP at week 4. The 0.065% concentration was also superior to latanoprost by up to 1.4 mm Hg for reduction from baseline at 8:00 am, 10:00 am, and 4:00 pm at week 4. NCX 470 was safe and well tolerated; conjunctival hyperemia was the most frequently reported adverse event.

Conclusions:

NCX 470 demonstrated dose-dependent reductions in IOP. The 0.042% and 0.065% concentrations demonstrated significantly greater reductions from baseline in mean diurnal IOP than latanoprost 0.005% at week 4, suggesting that higher concentrations may show even greater efficacy.
Exploring experiences associated with aortic stenosis diagnosis, treatment and life impact among middle-aged and older adults
Authors: Picou Kylie , Heard Debra G. , Shah Pinak B. , Arnold Suzanne V.
Published: April 2022

Background and purpose:

Although multiple studies have examined the clinical aspects of diagnosis, treatment, and management of patients with aortic stenosis (AS), limited data exist regarding patient experiences related to symptoms, diagnosis, treatment, and personal impacts of living with AS.

Methodology:

Adults aged ≥40 years diagnosed with AS were recruited and separated into three cohorts: medically managed, surgical aortic valve replacement (SAVR), and transcatheter aortic valve implantation (TAVI). Forty-five semi-structured interviews were conducted (15 per treatment group) via teleconference using open-ended questions and probes. Interview recordings were transcribed, and inductive thematic analyses were conducted.

Results:

The majority of participants were male (55.6%), White (95.6%), and non-Hispanic (93.3%). Participants noting longer times to diagnosis also reported mild symptom onset and experiences of misdiagnoses. Participants described a strong reliance on their health care professionals (HCPs) to guide them through their treatment decisions, which were influenced by the effects of anticoagulation, future valve interventions, and recovery. Medically managed participants reported having to make lifestyle modifications to manage symptoms, while participants who underwent TAVI or SAVR reported positive sentiments in their ability to return to normal life following their treatment.

Conclusions and implications:

Due to the varied experiences of AS patients, there is a need to improve patient resources to advance patient understanding and facilitate informed treatment decisions. Reported experiences also indicate a need for additional HCP education on early referral to a multidisciplinary heart valve team.
Telehealth for Pediatric Gastroenterology Care Now
Authors: Setty Mala , Mougey Edward B. , Berg Elizabeth , Rosen John M. , Lee Jennifer , Li B.U.K. , Venkatesh Rajitha D. , Franciosi James P.
Published: April 2022

Objectives:

With the coronavirus disease 2019 public health emergency (PHE), telehealth (TH) became essential for continued delivery of care. Members of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed the Telehealth for Pediatric Gastrointestinal Care Now (TPGCN) working group and rapidly organized a telemedicine webinar to provide education and guidance. We aim to describe the webinar development and prospectively assess the effectiveness of this webinar-based educational intervention.

Methods:

NASPGHAN members who registered for the TPGCN webinar received pre- and post-webinar surveys. Outcome measures included a modified Telehealth Acceptance Model (TAM) survey and a Student Evaluation of Educational Quality (SEEQ) standardized instrument.

Results:

Seven hundred seventy-six NASPGHAN members participated in the webinar, 147 (33%) completed the pre-webinar survey; of these, 25 of 147 (17%) completed a post-webinar survey. Before the PHE, 50.3% of the pre-webinar survey participants had no TH knowledge. Webinar participants trended to have increased acceptance of TH for follow-up visits (pre-webinar, 68% versus post-webinar, 81%; P = 0.15) and chronic disease care (pre-webinar, 57% vs post-webinar, 81%; P = 0.01). The overall acceptance of TH as shown by TAM pre-webinar was 1.74 ± 0.8, which improved to 1.62 ± 0.8 post-webinar (lower scores indicate greater acceptance; P < 0.001). SEEQ results indicate that webinar material was understandable (post-webinar, 95%). Participants found breakout sessions informative and enjoyable (post-webinar, 91%).

Conclusion:

The TPGCN TH webinar was an effective educational intervention that fostered increased TH usage for follow-up and chronic care visits, improved TAM scores, and was well received by participants as seen by high SEEQ scores. Sustained and expanded pediatric gastrointestinal TH usage beyond the coronavirus disease 2019 PHE is expected.