bluuebunny/crossref_metadata_2025 huggingface dataset:
Titratable partial aortic occlusion: Extending Zone I endovascular occlusion times
Authors: Gomez David , Naveed Asad , Rezende Joao , Dennis Bradley M. , Kundi Rishi , Benjamin Elizabeth , Lawless Ryan , Nguyen Jonathan , Duchesne Juan , Spalding Chance , Doris Stephanie , Van Skike Candice , Moore Ernest E. , Beckett Andrew
Published: May 2023

BACKGROUND

Extending the time to definitive hemorrhage control in noncompressible torso hemorrhage (NCTH) is of particular importance in the battlefield where transfer times are prolonged and NCTH remains the leading cause of death. While resuscitative endovascular balloon occlusion of the aorta is widely practiced as an initial adjunct for the management of NCTH, concerns for ischemic complications after 30 minutes of compete aortic occlusion deters many from zone 1 deployment. We hypothesize that extended zone 1 occlusion times will be enabled by novel purpose-built devices that allow for titratable partial aortic occlusion.

METHODS

This is a cross-sectional analysis describing pREBOA-PRO zone 1 deployment characteristics at seven level 1 trauma centers in the United States and Canada (March 30, 2021, and June 30, 2022). To compare patterns of zone 1 aortic occlusion, the AORTA registry was used. Data were limited to adult patients who underwent successful occlusion in zone 1 (2013–2022).

RESULTS

One hundred twenty-two patients pREBOA-PRO patients were included. Most catheters were deployed in zone 1 (n = 89 [73%]) with a median zone 1 total occlusion time of 40 minutes (interquartile range, 25–74). A sequence of complete followed by partial occlusion was used in 42% (n = 37) of zone 1 occlusion patients; a median of 76% (interquartile range, 60–87%) of total occlusion time was partial occlusion in this group. As was seen in the prospectively collected data, longer median total occlusion times were observed in the titratable occlusion group in AORTA compared with the complete occlusion group.

CONCLUSION

Longer zone 1 aortic occlusion times seen with titratable aortic occlusion catheters appear to be driven by the feasibility of controlled partial occlusion. The ability to extend safe aortic occlusion times may have significant impact to combat casualty care where exsanguination from NCTH is the leading source of potentially preventable deaths.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Extracellular Vesicle–associated GARP/TGFβ:LAP Mediates “Infectious” Allo-tolerance
Authors: Burlingham William J. , Jankowska-Gan Ewa , Fechner John H. , Little Christopher J. , Wang Jianxin , Hong Seungpyo , Molla Miraf , Sullivan Jeremy A. , Foley David P.
Published: May 2023

Background.

Here we test the hypothesis that, like CD81-associated “latent” IL35, the transforming growth factor (TGF)β:latency-associated peptide (LAP)/glycoprotein A repetitions predominant (GARP) complex was also tethered to small extracellular vesicles (sEVs), aka exosomes, produced by lymphocytes from allo-tolerized mice. Once these sEVs are taken up by conventional T cells, we also test whether TGFβ could be activated suppressing the local immune response.

Methods.

C57BL/6 mice were tolerized by i.p. injection of CBA/J splenocytes followed by anti-CD40L/CD154 antibody treatment on days 0, 2, and 4. On day 35, spleen and lymph nodes were extracted and isolated lymphocytes were restimulated with sonicates of CBA splenocytes overnight. sEVs were extracted from culture supernatants by ultracentrifugation (100 000g) and assayed for (a) the presence of TGFβ:LAP associated with tetraspanins CD81,CD63, and CD9 by enzyme-linked immunosorbent assay; (b) GARP, critical to membrane association of TGFβ:LAP and to activation from its latent form, as well as various TGFβ receptors; and (c) TGFβ-dependent function in 1° and 2° immunosuppression of tetanus toxoid-immunized B6 splenocytes using trans-vivo delayed–type hypersensitivity assay.

Results.

After tolerization, CBA-restimulated lymphocytes secreted GARP/TGFβ:LAP-coated extracellular vesicles. Like IL35 subunits, but unlike IL10, which was absent from ultracentrifuge pellets, GARP/TGFβ:LAP was mainly associated with CD81+ exosomes. sEV-bound GARP/TGFβ:LAP became active in both 1° and 2° immunosuppression, the latter requiring sEV uptake by “bystander” T cells and reexpression on the cell surface.

Conclusions.

Like other immune-suppressive components of the Treg exosome, which are produced in a latent form, exosomal GARP/TGFβ:LAP produced by allo-specific regulatory T cells undergoes either immediate activation (1° suppression) or internalization by naive T cells, followed by surface reexpression and subsequent activation (2°), to become suppressive. Our results imply a membrane-associated form of TGFβ:LAP that, like exosomal IL35, can target “bystander” lymphocytes. This new finding implicates exosomal TGFβ:LAP along with Treg-derived GARP as part of the infectious tolerance network.
Adjuvant Chemotherapy and Effect on Long-Term Survival in Ampullary Adenocarcinoma: A Multicenter Cohort Study
Authors: Shin Dong Woo , Lee Jae Min , Lee Jong-chan , Lee Hee Seung , Yoon Seung Bae , Jang Dong Kee , Park Joo Kyung , Jung Min Kyu , Lee Yoon Suk , Hwang Jin-Hyeok
Published: May 2023

BACKGROUND:

The role of adjuvant chemotherapy (AC) in patients with ampullary adenocarcinoma (AA) remains controversial. This study aimed to determine if AC could improve the prognosis of patients with resected AA.

STUDY DESIGN:

This study enrolled patients diagnosed with AA at 9 tertiary teaching hospitals. Patients who did and did not receive AC were matched 1:1 using propensity score. The overall survival (OS) and recurrence-free survival (RFS) were compared between the 2 groups.

RESULTS:

Of the 1,057 patients with AA, 883 underwent curative-intent pancreaticoduodenectomy, and 255 received AC. Because patients with advanced-stage AA received AC more frequently, the no AC group unexpectedly had a longer OS (not reached vs 78.6 months; p < 0.001) and RFS (not reached vs 18.7 months; p < 0.001) than did the AC group in the unmatched cohort. In the propensity score–matched cohort (n = 296), no difference between the 2 groups in terms of OS (95.9 vs 89.8 months, p = 0.303) and RFS (not reached vs 25.5 months; p = 0.069) was found. By subgroup analysis, patients with advanced stage (pT4 or pN1-2) showed longer OS in the AC group than in the no AC group (not reached vs 15.7 months, p = 0.007: 89.8 vs 24.2 months, p = 0.006, respectively). There was no difference in RFS according to AC in the propensity score–matched cohort.

CONCLUSIONS:

Given its favorable long-term outcomes, AC can be recommended for patients with resected AA, especially those in the advanced stage (pT4 or pN1-2).
Steering herds away from dangers in dynamic environments
Authors: Van Havermaet Stef , Simoens Pieter , Landgraf Tim , Khaluf Yara
Published: May 2023

Shepherding, the task of guiding a herd of autonomous individuals in a desired direction, is an essential skill to herd animals, enable crowd control and rescue from danger. Equipping robots with the capability of shepherding would allow performing such tasks with increased efficiency and reduced labour costs. So far, only single-robot or centralized multi-robot solutions have been proposed. The former is unable to observe dangers at any place surrounding the herd, and the latter does not generalize to unconstrained environments. Therefore, we propose a decentralized control algorithm for multi-robot shepherding, where the robots maintain a caging pattern around the herd to detect potential nearby dangers. When danger is detected, part of the robot swarm positions itself in order to repel the herd towards a safer region. We study the performance of our algorithm for different collective motion models of the herd. We task the robots to shepherd a herd to safety in two dynamic scenarios: (i) to avoid dangerous patches appearing over time and (ii) to remain inside a safe circular enclosure. Simulations show that the robots are always successful in shepherding when the herd remains cohesive, and enough robots are deployed.
Topological effects of a global monopole on a spherical quantum dot
Authors: Bakke Knut
Published: May 2023

We consider a spherical quantum dot described by an attractive short-range potential and search for topological effects of a global monopole on it. The attractive short-range potential is built from the power-exponential potential model in Ciurla
et al.
(2022
Physica E
15
, 261–268 (
doi:10.1016/S1386-9477(02)00572-6
)), where we focus on a particular case proposed by this quantum dot model. In search of bound states, we deal with

s

-waves. We thus obtain the energy eigenvalues and discuss the effects of the topology of the global monopole on them. Further, we extend our discussion to the quantum revivals.
Elastic wave dispersion in layered media with suture joints: influence of structural hierarchy and viscoelasticity
Authors: Ongaro Federica , Bosia Federico , Pugno Nicola M.
Published: May 2023

Suture joints contribute to the exceptional combination of stiffness, strength, toughness and efficient load bearing and transmission of many biological structures like the cranium or ammonite fossil shells. However, their role in the attenuation of vibrations and effect on dynamic loads is less clear. Moreover, the self-similar hierarchical geometry often associated with suture joints renders its treatment with standard numerical approaches computationally prohibitive. To address this problem, this paper investigates the dynamic response of periodic layered media with suture joints using an analytical approach based on material homogenization. A general trapezoidal suture geometry is considered together with the fundamental ingredients of hierarchy and viscoelasticity. The Spectral Element Method and Bloch theorem are used to derive the dispersion relation and band diagram of the system, including propagating and evanescent dispersion modes. A strong influence of the suture morphology and material properties emerges, and the analysis reveals an important advantage of adding hierarchy, i.e. the possibility of simultaneously obtaining wider bandgaps and their shift to higher frequencies. A synergy between hierarchy and structure is also observed, providing superior levels of wave attenuation. These findings suggest a possible design concept for bioinspired devices with efficient and tailorable wave attenuation properties.
Persistent currents, revival time and effects of rotation on an attractive inverse-square-type potential in a magnetic quadrupole moment system
Authors: Vieira S. L. R. , Bakke K.
Published: May 2023

We study the appearance of an Aharonov–Bohm-type effect around a cylindrical cavity in a magnetic quadrupole moment system in a rotating reference frame. The analogue of the Aharonov–Bohm-type effect of bound states arises from the interaction of the magnetic quadrupole moment of a neutral particle with an induced electric field when the neutral particle is subject to an attractive inverse-square-type potential, which in turn stems from the interaction of the magnetic quadrupole moment of a neutral particle with a magnetic field. We also discuss how the effects of rotation modify the degeneracy of the energy levels in contrast to the case of absence of rotation. Besides this, we calculate the revival time and the persistent currents.
An extended shoving model for dynamic fluctuation of glass transition in amorphous polymer towards cooperative shape-memory effect
Authors: Liu Jingyun , Lu Haibao , Elmarakbi Ahmed , Fu Yong-Qing
Published: May 2023

Phase transition theory is a powerful approach to study shape-memory effect (SME) and dynamic relaxation behaviour in amorphous shape-memory polymers (SMPs) undergoing glass transition processes. However, previous studies are mostly limited to building-up of experimental models, mainly due to poor understanding of dynamic fluctuation of glass transition. In this study, the dynamic fluctuation of glass transition in the amorphous SMPs, whose thermodynamic SME is governed by the phase transition theory, was investigated using a shoving model. A constitutive relationship between potential energy and cooperatively rearranging region (CRR) volume is firstly developed to explore the working principle of phase transition in the thermodynamic SME of amorphous SMPs, based on the shoving model and Adam–Gibbs domain size model. The effect of CRR volume on the phase transition is further formulated using the strain function, and then employed to develop a constitutive stress–strain equation based on the extended Maxwell model. The working principles of cooperative SME and dynamic relaxation behaviours have been explored and discussed. Finally, the effectiveness of the analytical results obtained using the proposed model has been verified using the experimental results of amorphous SMPs reported in literature.
Higher temperature variability in deforested mountain regions impacts the competitive advantage of nocturnal species
Authors: Chan Shih-Fan , Rubenstein Dustin R. , Chen I-Ching , Fan Yu-Meng , Tsai Hsiang-Yu , Zheng Yuan-Wen , Shen Sheng-Feng
Published: May 2023

Deforestation is a major contributor to biodiversity loss, yet the impact of forest loss on daily microclimate variability and its implications for species with different daily activity patterns remain poorly understood. Using a recently developed microclimate model, we investigated the effects of deforestation on the daily temperature range (DTR) in low-elevation tropical regions and high-elevation temperate regions. Our results show that deforestation substantially increases DTR in these areas, suggesting a potential impact on species interactions. To test this hypothesis, we studied the competitive interactions between nocturnal burying beetles and all-day-active blowfly maggots in forested and deforested habitats in Taiwan. We show that deforestation leads to increased DTR at higher elevations, which enhances the competitiveness of blowfly maggots during the day and leads to a higher failure rate of carcass burial by the beetles at night. Thus, deforestation-induced temperature variability not only modulates exploitative competition between species with different daily activity patterns, but also likely exacerbates the negative impacts of climate change on nocturnal organisms. In order to limit potential adverse effects on species interactions and their ecological functions, our study highlights the need to protect forests, especially in areas where deforestation can greatly alter temperature variability.
Massilia agrisoli sp. nov., isolated from rhizospheric soil of banana
Authors: Huq Md. Amdadul , Ma Juncai , Srinivasan Sathiyaraj , Parvez Md. Anowar Khasru , Rahman M. Mizanur , Naserkheil Masoumeh , Abuhena Md. , Maitra Pulak , Islam Fahadul , NAM Kihong , Park Jong-Hyun , Akter Shahina
Published: May 2023

A Gram-stain-negative, aerobic, short rod-shaped and motile novel bacterial strain, designated MAHUQ-52T, was isolated from the rhizospheric soil of a banana plant. Colonies grew at 10–35 °C (optimum, 28 °C), pH 6.0–9.5 (optimum, pH 7.0–7.5), and in the presence of 0–1.0 % NaCl (optimum 0 %). The strain was positive for catalase and oxidase tests, as well as hydrolysis of gelatin, casein, starch and Tween 20. Based on the results of phylogenetic analysis using 16S rRNA gene and genome sequences, strain MAHUQ-52T clustered together within the genus

Massilia

. Strain MAHUQ-52T was closely related to

Massilia soli

R798T (98.6 %) and

Massilia polaris

RP-1-19T (98.3 %). The novel strain MAHUQ-52T has a draft genome size of 4 677 454 bp (25 contigs), annotated with 4193 protein-coding genes, 64 tRNA and 19 rRNA genes. The genomic DNA G+C content was 63.0 %. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between strain MAHUQ-52T and closely related type strains were ≤88.4 and 35.8 %, respectively. The only respiratory quinone was ubiquinone-8. The major fatty acids were identified as C16 : 0 and summed feature 3 (C15 : 0 iso 2-OH and/or C16 : 1
 ω7c). Strain MAHUQ-52T contained phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol as the major polar lipids. On the basis of dDDH and ANI values, as well as genotypic, chemotaxonomic and physiological data, strain MAHUQ-52T represents a novel species within the genus

Massilia

, for which the name Massilia agrisoli sp. nov. is proposed, with MAHUQ-52T (=KACC 21999T=CGMCC 1.18577T) as the type strain.
Stakelama marina sp. nov., isolated from seawater of the Tangyin hydrothermal field in the Okinawa Trough
Authors: Wang Shuang , Cao Xiaochen , Liu Lijun , Liu Ronghua , Bian Zeran , Zhang Xiao-Hua , Yu Min
Published: May 2023

A Gram-stain-negative, strictly aerobic, rod-shaped and non-flagellated marine bacterium, designated strain LXI357T, was isolated from deep-sea water sampled at the Tangyin hydrothermal field in the Okinawa Trough. The growth temperature range was 20–45 °C (optimum, 28 °C). Strain LXI357T was also able to grow at pH 5.0–7.5 (optimum, pH 6.0–7.0) and in the presence of 0.5–11 % (optimum, 7%, w/v) NaCl. Strain LXI357T was oxidase-negative and catalase-positive. The predominant fatty acids were C18 : 1
 ω7c and C16 : 0. The major polar lipids of strain LXI357T contained phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phospholipid, sphingoglycolipid, diphosphatidylglycero and an unidentified aminolipid. Based on the results of 16S rRNA gene sequence analysis, strain LXI357T belonged to the genus

Stakelama

and was most closely related to

Stakelama flava

CBK3Z-3T (96.28%, 16S rRNA gene sequence similarity), followed by

Stakelama algicida

Yeonmyeong 1-13T (95.67%),

Stakelama pacifica

JLT832T (95.46%) and

Sphingosinicella vermicomposti

YC7378T (95.43%). Genome relatedness between strain LXI357T and

Stakelama flava

CBK3Z-3T was computed using average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity, with values of 76.02, 20.9 and 71.1 %, respectively. The genomic DNA G+C content of strain LXI357T is 64.1 mol%. In addition, strain LXI357T has multiple genes related to sulphur metabolism, including genes encoding for the Sox system. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished strain LXI357T from its closest phylogenetic neighbours. According to the results of polyphasic analyses, strain LXI357T is considered to represent a novel species of the genus

Stakelama

, for which the name Stakelama marina sp. nov. is proposed. The type strain is LXI357T (=MCCC 1K06076T=KCTC 82726T).
H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in paediatric high-grade glioma cells
Authors: Leszczynska Katarzyna B. , Pereira de Freitas Amanda , Jayaprakash Chinchu , Dzwigonska Monika , Wojnicki Kamil , Gielniewski Bartlomiej , Szadkowska Paulina , Kaza Beata , Ciolkowski Maciej K. , Trubicka Joanna , Grajkowska Wieslawa , Kaminska Bozena , Mieczkowski Jakub
Published: May 2023

Diffuse intrinsic pontine gliomas (DIPG) are deadly paediatric brain tumours, non-resectable due to brainstem localisation and diffusive growth. Patients with DIPG have a dismal prognosis of 9-12 months of survival with no effective therapy. Over 80% of DIPGs harbour a mutation in histone 3 (H3.3 or H3.1) resulting in a lysine to methionine substitution (H3K27M). H3K27M causes global epigenetic alterations (a loss of H3K27 trimethylation and an increase in H3K27 acetylation) resulting in aberrant gene expression. To date, no therapeutic strategy exists to suppress the levels of oncogenic H3K27M.

We show that pan-HDAC inhibitors (HDACi) lead to the temporary but significant reduction in the H3.3K27M protein (up to 80%) in multiple glioma cell lines expressing the H3.3K27M histone variant, without changes in theH3F3AmRNA expression. The H3.3K27M occupancy at the chromatin is greatly reduced upon HDACi (SB939) treatment, as shown by ChIPseq analysis. H3.3K27M loss is most striking at SB939-upregulated genes suggesting the role in repression of these genes. In addition, genes previously reported as H3K27M-dependent become downregulated in response to SB939 treatment. We discover that the SB939-mediated loss of H3.3K27M is partially blocked by a lysosomal inhibitor, chloroquine. Moreover, the loss of H3.3K27M is facilitated by co-occurrence of H2A.Z, as evidenced by the knock-down of H2A.Z histone isoforms. ChIPseq analysis confirms the occupancy of H3.3K27M and H2A.Z at the same SB939-inducible genes.

Altogether, we provide new insight into disease-specific mechanism of HDAC inhibition and demonstrate pharmacological modulation of the oncogenic H3.3K27M protein levels. These findings open a new possibility to directly target the H3.3K27M oncohistone, which may be exploited in future therapies.
Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity
Authors: Benede Ntombi S. B. , Tincho Marius B. , Walters Avril , Subbiah Vennesa , Ngomti Amkele , Baguma Richard , Butters Claire , Mennen Mathilda , Skelem Sango , Adriaanse Marguerite , van Graan Strauss , Balla Sashkia R. , Moyo-Gwete Thandeka , Moore Penny L. , Botha Maresa , Workman Lesley , Zar Heather J. , Ntusi Ntobeko A. B. , Zühlke Liesl , Webb Kate , Riou Catherine , Burgers Wendy A. , Keeton Roanne S.
Published: May 2023

SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children.
Neuroactive metabolites and bile acids are altered in extremely premature infants with brain injury
Authors: Pristner Manuel , Wasinger Daniel , Seki David , Klebermaß-Schrehof Katrin , Berger Angelika , Berry David , Wisgrill Lukas , Warth Benedikt
Published: May 2023

The gut microbiome has been associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigated the longitudinal fecal and plasma metabolome of 51 extremely premature infants using LC-HRMS-based untargeted metabolomics. This was expanded by an investigation of bile acids and amidated bile acid conjugates in feces and plasma by LC-MS/MS-based targeted metabolomics. The resulting data was integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor and T-cell profiles. We identified an early onset of differentiation in neuroactive metabolites and bile acids between infants with and without brain injury. We detected several bacterially-derived bile acid amino acid conjugates and secondary bile acids in the plasma already three days after delivery, indicating the early establishment of a metabolically active gut microbiome. These results give new insights into the early life metabolome of extremely premature infants.
Symptom onset and cellular pathology in facioscapulohumeral muscular dystrophy is accelerated by cigarette smoking
Authors: Banerji Christopher R. S. , Heher Philipp , Hogan John , Katz Natalie , Haidar Husain Bin , Keegan Michael D. , Cernik Colin , Tawil Rabi , Patel Ketan , Zammit Peter S. , Statland Jeffery M.
Published: May 2023

Facioscapulohumeral muscular dystrophy (FSHD) is an incurable skeletal myopathy. In absence of therapy, lifestyle factors impacting disease progression are important for clinical management. Monozygotic twins with FSHD often exhibit dramatically different disease progression, indicating existence of environmental disease modifiers. Here we analyse the USA National Registry for Myotonic Dystrophy & Facioscapulohumeral Dystrophy, comprising 511 FSHD1 patients followed up annually for an average of 8 years. This multimodal, longitudinal dataset comprises 189 baseline and 37 annually assessed features. We developed a workflow for prospective cohort analysis and identify cigarette smoking as associated with a two-fold increase in risk of facial and lower limb involvement in FSHD1 patients. Our definition of lower limb involvement includes inability to run and climb steps unaided, important functional outcomes for FSHD patients. We then employed an assay to test the effects of cigarette smoke extract on human myoblasts in vitro. Cigarette smoke extract drove disproportionate defects in proliferation and myogenic differentiation of FSHD1 patient-derived myoblasts, compared to matched controls. Mitochondrial function was also inordinately affected in FSHD1 myoblasts exposed to cigarette smoke extract, with increased mitochondrial membrane potential and mitochondrial radical oxygen species (mitoROS) generation. Our findings support recommending smoking cessation in clinical management of FSHD.
Investigation of a Behavioral Interruption Management Strategy on Improving Medication Administration Safety and Efficiency: A Feasibility Study
Authors: Schroers Ginger , Pfieffer Jill , Tell Dina , O’Rourke Jenny
Published: May 2023

Background

Worldwide, interruptions are pervasive during nurse medication administration and associated with increased frequency and severity of errors. Interruptions also decrease task efficiency which can lead to delayed or omitted patient care. Interruptions cannot always be avoided in healthcare settings; thus, researchers recommend the use of interruption management strategies to mitigate interruptions’ negative effects.

Aims

To investigate the feasibility and potential of a behavioral interruption management strategy to mitigate medication errors and improve task efficiency.

Design

Multi-methods, two groups, repeated measures, pre-posttest design.

Methods

Data were collected January-March 2023. Volunteer undergraduate nursing students were randomly assigned to a control or intervention group. The intervention group received education and training on an interruption management strategy. Quantitative data were collected across three timepoints via direct observation of independent demonstrations of simulated medication administration. The simulated scenarios contained embedded interruptions. Outcomes measured included errors, medication preparation duration, and duration of time to implement the interruption management strategy. Descriptive statistics were analyzed using Microsoft Excel. Qualitative data of participants’ perceptions and use of the strategy were collected via semi-structured interviews.

Thematic analysis was performed.

Reporting Method

Equator guidelines were followed using the STROBE reporting method for the observed quantitative data. SRQR guidelines were followed in reporting the qualitative data.

Results

Nineteen students participated in the study. Intervention group participants had larger improvements in errors and task durations compared to the control group. Implementation of the strategy averaged four seconds. Participants described the strategy as easy to use and remember, and voiced using the strategy outside of the study.

Conclusions

Findings demonstrate that the study-described behavioral interruption management strategy was feasible to teach and implement, and associated with decreased errors and improved task efficiency. Use of the strategy has implications to increase patient safety through improved medication administration safety and efficiency. Future studies are recommended to gain a better understanding of the strategy’s effectiveness.
Emotional overeating affected nine in ten female students during the COVID-19 University closure: A cross-sectional study in France
Authors: Constant Aymery , Fortier Alexandra , Serrand Yann , Bannier Elise , Moirand Romain , Thibault Ronan , Coquery Nicolas , Godet Ambre , Val-Laillet David
Published: May 2023

Objectives

To estimate the proportion of female university students reporting overeating (EO) in response to emotions during the COVID-19 university closures, and to investigate social and psychological factors associated with this response to stress.

Design

Online survey gathered sociodemographic data, alcohol/drugs use disorders, boredom proneness and impulsivity using validated questionnaires, and EO using the Emotional Overeating Questionnaire (EOQ) assessing eating in response to six emotions (anxiety, sadness, loneliness, anger, fatigue, happiness), whose structure remains to be determined.

Participants

Sample of 302 female students from Rennes University, France.

Main Outcome Measure

Frequencies of emotional overeating.

Analysis

The frequency of emotional overeating was expressed for each emotion as percentages. Exploratory Factor analyses (EFA) were used to determine EOQ structure and provide an index of all EOQ items used for further analysis. Linear regression models were used to explore relationships between EO and others covariates.

Results

Nine in ten participants reported intermittent EO in the last 28 days, mostly during 6 to 12 days, in response to Anxiety (75.5%), Sadness (64.5%), Happiness (59.9%), Loneliness (57.9%), Tiredness (51.7%), and to a lesser extent to Anger (31.1%). EFA evidenced a one-factor latent variable reflecting “Distress-Induced Overeating” positively correlated with internal boredom proneness, tobacco use, attentional impulsivity, inability to resist emotional cues, and loss of control over food intake, and negatively with age and well-being. EO was unrelated to body mass index or substance abuse.

Conclusion and Implications

Nine in ten female students reported emotional overeating during the COVID-19 university closure. This response to stress was related to eating tendencies typical of young women, but also to personality/behavioral patterns such as boredom and impulsivity proneness. Better understanding of the mechanisms underlying EO in response to stress and lack of external/social stimulation would improve preventive interventions.
Patients with sickle cell disease presented dysregulated plasma Rb/K ratio and Gamma-glutamyl cycle in red blood cells
Authors: Bhatt Shruti , Mohapatra Amit Kumar , Rajesh Apratim Sai , Meher Satyabrata , Panda Pradip Kumar , Nanda Ranjan Kumar , Kundu Suman
Published: May 2023

Patients suffering from sickle cell disease (SCD) present with multifactorial pathology, and a detailed understanding of it may help to develop novel therapeutics. In this study, the plasma elemental (24Mg,44Ca,57Fe,63Cu,66Zn,77Se,85Rb,208Pb, and39K) levels of SCD patients (n=10, male: 50%) and control groups (trait and healthy; n=10 each; male: 50%) were profiled using inductively coupled plasma mass spectrometry (ICP-MS). Additionally, comparative global erythrocyte metabolomics of SCD (n=5, male:100%) and healthy controls (n=5, male:100%) were carried out using liquid chromatography-mass spectrometry (LC-MS). SCD patients had higher plasma24Mg,44Ca,66Zn,208Pb, and39K levels and lower levels of57Fe,77Se, and85Rb compared to controls. These changes in elemental levels, with a decreased Rb/K ratio in the SCD group, may explain the observed frequent hemolysis and severe dehydration with oxidative stress in patients. Mass spectrometry analysis of red blood cells (RBCs of SCD (n=5) and healthy controls (n=5) identified 442 unique metabolic features which separately clustered both the study groups in principal component analysis (PCA). A set of 136 features showed differential (p<0.05; log2fold change>±1) regulation and was involved in D-glutamine/D-glutamate, sphingolipid, arginine biosynthesis, glutathione and glycine, serine and threonine metabolism. Interestingly, higher pyroglutamic acid levels were observed in the sickle shaped-RBCs indicating a perturbed gamma-glutamyl pathway in SCD patients. Supplementation of the depleted trace metals and targeting the perturbed metabolic pathways in the RBCs of SCD patients may provide avenues for the development of alternate therapeutics.

Graphical abstract
Plasma neurofilament light chain predicts Alzheimer’s disease in patients with subjective cognitive decline and mild cognitive impairment: a longitudinal study
Authors: Mazzeo Salvatore , Bagnoli Silvia , Ingannato Assunta , Padiglioni Sonia , Giacomucci Giulia , Manganelli Alberto , Moschini Valentina , Balestrini Juri , Cavaliere Arianna , Morinelli Carmen , Galdo Giulia , Emiliani Filippo , Piazzesi Diletta , Crucitti Chiara , Frigerio Daniele , Polito Cristina , Berti Valentina , Sorbi Sandro , Nacmias Benedetta , Bessi Valentina
Published: May 2023

Background

We aimed to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting Alzheimer’s disease (AD) and the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI).

Methods

This longitudinal cohort study involved 140 patients (50 with SCD, 73 with MCI, and 22 with AD dementia [AD-D]) who underwent plasma NfL and AD biomarker assessments (CSF, amyloid-PET, and18F-FDG-PET) at baseline. They were rated according to the A/T/N system and followed up for a mean time of 2.72±0.95 years to detect progression from SCD to MCI and from MCI to AD. Forty-eight patients (19 SCD, 29 MCI) also underwent plasma NfL measurements after two years after baseline.

Results

At baseline, plasma NfL detected patients with biomarker profiles consistent with AD (A+/T+/N+ or A+/T+/N-) with high accuracy (AUC=0.82). We identified cut-off value of

19.45 pg/mL for SCD and 20.45 pg/mL for MCI. During follow-up, nine SCD patients progressed to MCI (p-SCD), and 14 MCI patients developed AD dementia (p-MCI). The previously identified cut-off values provided good accuracy in identifying p-SCD (80% [95% C.I.=65.69:94.31]). The rate of NfL change was higher in p-MCI (3.52±4.06 pg/mL) compared to np-SCD (0.81±1.25 pg/mL) and np-MCI (−0.13±3.24 pg/mL) patients. A rate of change lower than 1.64 pg/mL per year accurately excluded progression from MCI to AD (AUC=0.954).

Conclusion

Plasma NfL concentration and change over time may be a reliable, non-invasive tool to detect AD and the progression of cognitive decline at the earliest stages of the disease.

Key messages

What is already known on this topic

Plasma NfL increase in SCD, MCI and AD and longitudinal changes in NfL are related to changes in brain atrophy and cognitive outcomes in AD. Nevertheless, the clinical value of plasma NfL in non-demented patients has been poorly explored.

What this study adds

Plasma NfL accurately predicts AD pathology and progression of cognitive decline in SCD and MCI. Repeated measurements of NfL may further increase the accuracy of this biomarker

How this study might affect research, practice, or policy

Given its accessibility, blood-based NfL can assist clinicians in determining the optimal personalized diagnostic and therapeutic approach for individuals presenting with SCD or MCI, providing insights into the underlying biological mechanisms of cognitive decline, even in primary care settings.
Glymphatic system impairment contributes to the formation of brain edema after ischemic stroke
Authors: Zhu Juan , Mo Jiaying , Liu Kewei , Chen Quanfeng , Li Zheqi , He Yihua , Chang Yuan , Lin Chuman , Yu Mingjia , Xu Yikai , Tan Xiangliang , Huang Kaibin , Pan Suyue
Published: May 2023

The blood-brain barrier (BBB) damage has traditionally been considered to determine the occurrence and development of post-stroke brain edema, a devastating and life-threatening complication. However, no treatment strategy targeting BBB damage has been proven clinically effective in ameliorating brain edema. Here, we found that the extravasation of protein-rich fluids into the brain was not temporally correlated with edema formation after middle cerebral artery occlusion (MCAO) in mice, as brain edema reabsorption preceded BBB closure. Strikingly, the time course of edema progression matched well with the glymphatic system (GS) dysfunction after MCAO. Pharmacological enhancement of the GS function significantly alleviated brain edema developed on day 2 after MCAO, accompanied by less deposition of Aβ and better cognitive function. Conversely, functional suppression of the GS delayed the absorption of brain edema on day 7 after MCAO. Moreover, patients with ischemic stroke revealed a consistent trend of GS dysfunction after reperfusion as MCAO mice, which was correlated with the severity of brain edema and functional outcomes. Collectively, these findings indicate that the GS is a key contributor to the formation of brain edema after ischemic stroke, and targeting the GS may be a promising strategy for the treatment of brain edema in ischemic stroke.

One Sentence Summary

The function of the glymphatic system is a key factor in determining the formation or resolution of brain edema after ischemic stroke

Graphical Abstract
Brain fingerprint changes across the menstrual cycle correlate with emotional state
Authors: Cipriano Lorenzo , Liparoti Marianna , Lopez Emahnuel Troisi , Sarno Laura , Lucidi Fabio , Sorrentino Pierpaolo , Sorrentino Giuseppe
Published: May 2023

Background

Menstrual cycle (MC) is the cyclical phenomenon with the greatest impact on women’s mood and behavior. To date, little is known about the potential mechanism and neuroanatomical correlates of behavioral and emotional fluctuations across the MC. Brain connectome fingerprinting, a recently introduced technique in the field of brain network analysis, represents a valid approach in assessing the subject-specific connectivity and in predicting clinical impairment in several neurological diseases. Nevertheless, its performance, and clinical utility, in healthy individuals has not yet been investigated.

Methods

We conducted the Clinical Connectome Fingerprint (CCF) analysis on source-reconstructed magnetoencephalography signals in a cohort of 24 women across the MC.

Results

All the parameters of identifiability did not differ according to the MC phases. The peri-ovulatory and mid-luteal phases showed a less stable, more variable over time, brain connectome compared to the early follicular phase. This difference in brain connectome stability (especially in the posterior brain regions) was able to significantly predict self-esteem, wellbeing, and mood.

Conclusion

These results confirm the high reliability of the CCF and its independence from the MC phases and, at the same time, provide neuroanatomical correlates of the emotional and mood aspects that change across the MC.
A rare genetic disorder provides insights into mechanisms of early-onset neurodegeneration
Authors: Badja Cherif , Momen Sophie , Koh Gene Ching Cheik , Boushaki Soraya , Roumeliotis Theodoros I. , Kozik Zuza , Jones Ian , Bousgouni Vicky , Dias João M. L. , Krokidis Marios G. , Young Jamie , Chen Hongwei , Yang Ming , Docquier France , Memari Yasin , Valcarcel-Jimenez Lorea , Gupta Komal , Kong Li Ren , Fawcett Heather , Robert Florian , Zhao Salome , Degasperi Andrea , Davies Helen , Harris Rebecca , Frezza Christian , Chatgilialoglu Chryssostomos , Sarkany Robert , Lehmann Alan , Bakal Chris , Choudhary Jyoti , Fassihi Hiva , Nik-Zainal Serena
Published: May 2023

Xeroderma pigmentosum (XP) is characterized by defective repair of ultraviolet radiation(UVR)-induced DNA damage. Patients have UVR hypersensitivity and increased skin cancer risk. Effective photoprotection has reduced childhood cancer-related deaths, but revealed adolescence-onset neurodegeneration, arising through unknown mechanisms. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We find endoplasmic reticulum stress is upregulated, preceded by oxidative stress, causing substantial 5’,8-cyclopurine and 8-oxopurine DNA damage. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity improves phenotypes, albeit inadequately, implying that early detection/prevention strategies are necessary to produce clinically impactful outcomes. Thus, we develop an early detection assay predicting neurodegeneration in at-risk patients.
40HZ photoacoustic interventions combined with blue light improve brain function and sleep quality in a healthy population
Authors: Xu Xiaojun , Gong Zhuping , Jin Kaixiu , Huang Peiyu , Zhou Cheng , Zeng Qingze , Teng Junhu , Liu Ziyu , Zhang Huajiang , Xu Qian , Chen Yanling , Fang Cong , Zhang Minming
Published: May 2023

Recent studies suggest that 40Hz photoacoustic stimulation is beneficial for improving cognition, and is safe and effective in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). It has been reported that the healthy population responds more strongly to the 40 Hz intervention compared to MCI and AD patients. Therefore, the aim of this study was to explore the effectiveness of 40 Hz photoacoustics in preventing cognitive impairment and improving sleep quality in the healthy population.

Four weeks of 40 Hz intervention significantly improved sleep quality (PSQI) (p=0.028) and enhanced functional connectivity in the hippocampus and default mode network (DMN) (in the cognitively impaired population, functional connectivity showed a decreasing trend). These results were consistent with findings from the FDA clinical trial on MCI/AD patients that showed enhanced connectivity of the core regions PCC and mPFC within the DMN network. No serious adverse effects were reported throughout the intervention.

This study is the first to validate the efficacy and safety of a 40 Hz photoacoustic intervention in a healthy population, suggesting its potential in preventing cognitive decline in a healthy population.
Neurofeedback-enabled beta power control with a fully implanted DBS system in patients with Parkinson’s disease
Authors: Rohr-Fukuma Manabu , Stieglitz Lennart H. , Bujan Bartosz , Jedrysiak Piotr , Oertel Markus F. , Salzmann Lena , Baumann Christian R. , Imbach Lukas L. , Gassert Roger , Bichsel Oliver
Published: May 2023

Parkinsonian motor symptoms are linked to pathologically increased beta oscillations in the basal ganglia. Studies with externalised deep brain stimulation electrodes showed that Parkinson patients were able to rapidly gain control over these pathological basal ganglia signals through neurofeedback. Studies with fully implanted deep brain stimulation systems duplicating these promising results are required to grant transferability to daily application. In this study, seven patients with idiopathic Parkinson’s disease and one with familial Parkinson’s disease were included. In a postoperative setting, beta oscillations from the subthalamic nucleus were recorded with a fully implanted deep brain stimulation system and converted to a real-time visual feedback signal. Participants were instructed to perform bidirectional neurofeedback tasks with the aim to modulate these oscillations. While receiving regular medication and deep brain stimulation, participants were able to significantly improve their neurofeedback ability and achieved a significant decrease of subthalamic beta power (median reduction of 31% in the final neurofeedback block). We could demonstrate that a fully implanted deep brain stimulation system can provide visual neurofeedback enabling patients with Parkinson’s disease to rapidly control pathological subthalamic beta oscillations.
Wastewater-based reproduction numbers and projections of COVID-19 cases in multiple cities in Japan, 2022
Authors: Miyazawa Shogo , Wong TingSam , Ito Genta , Iwamoto Ryo , Watanabe Kozo , van Boven Michiel , Wallinga Jacco , Miura Fuminari
Published: May 2023

Background

Wastewater surveillance has expanded globally to monitor the spread of infectious diseases. An inherent challenge is substantial noise and bias in wastewater data due to their sampling and quantification process, leading to the limited applicability of wastewater surveillance as a monitoring tool and the difficulty.

Aim

In this study, we present an analytical framework for capturing the growth trend of circulating infections from wastewater data and conducting scenario analyses to guide policy decisions.

Methods

We developed a mathematical model for translating the observed SARS-CoV-2 viral load in wastewater into effective reproduction numbers. We used an extended Kalman filter to infer underlying transmissions by smoothing out observational noise. We also illustrated the impact of different countermeasures such as expanded vaccinations and non-pharmaceutical interventions on the projected number of cases using three study areas in Japan as an example.

Results

Our analyses showed an adequate fit to the data, regardless of study area and virus quantification method, and the estimated reproduction numbers derived from wastewater data were consistent with notification-based reproduction numbers. Our projections showed that a 10-20% increase in vaccination coverage or a 10% reduction in contact rate may suffice to initiate a declining trend in study areas.

Conclusion

Our study demonstrates how wastewater data can be used to track reproduction numbers and perform scenario modelling to inform policy decisions. The proposed framework complements conventional clinical surveillance, especially when reliable and timely epidemiological data are not available.
Center Related Variation in Hospitalization Cost for Patients undergoing Percutaneous Left Atrial Appendage Occlusion
Authors: Patil Shivaraj , Rojulpote Chaitanya , Bhattaru Abhijit , Atri Avica , Atri Viha , Khraisha Ola , Mainigi Sumeet
Published: May 2023

Background

The commercial use of percutaneous LAAO with the Watchman device is increasing in the United States. The purpose of this study was to evaluate center related variation in total hospital costs for Watchman device implantation and identify factors associated with high hospital costs at a national level.

Methods

All adults undergoing elective LAAO with Watchman were identified in the 2016 to 2018 National Inpatient Database. Mixed models were used to evaluate the impact of center on total hospital costs adjusting for patient and center characteristics, and length of stay.

Results

A total of 30,175 patients underwent Watchman device implantation at a median cost of $24,500 and demonstrated significant variability across admissions (inter-decile range, $13,900-37,000). Nearly 13% of the variability in patient-level costs was related to the center performing the procedure rather than patient factors. Higher volume centers had lower total costs and demonstrated lesser total cost variation. Centers with low procedural volume, occurrence of procedural complications, congestive heart failure, and length of stay were independent predictors of a high-cost hospitalization. Though complications were associated with increased expenditure, they did not explain the observed cost variation related to the center.

Conclusion

A significant proportion of variation in total hospital cost was attributable to the center performing the procedure. Addressing variability of Watchman-related costs is necessary to achieve high-quality value-based care.