bluuebunny/crossref_metadata_2025 huggingface dataset:
Sparse matrix multiplication in a record-low power self-rectifying memristor array for scientific computing
Authors: Li Jiancong , Ren Sheng-guang , Li Yi , Yang Ling , Yu Yinjie , Ni Run , Zhou Houji , Bao Han , He Yuhui , Chen Jia , Jia Han , Miao Xiangshui
Published: June 2023

Memristor-enabled in-memory computing provides an unconventional computing paradigm to surpass the energy efficiency of von Neumann computers. Owing to the limitation of the computing mechanism, while the crossbar structure is desirable for dense computation, the system’s energy and area efficiency degrade substantially in performing sparse computation tasks, such as scientific computing. In this work, we report a high-efficiency in-memory sparse computing system based on a self-rectifying memristor array. This system originates from an analog computing mechanism that is motivated by the device’s self-rectifying nature, which can achieve an overall performance of ~97 to ~11 TOPS/W for 2- to 8-bit sparse computation when processing practical scientific computing tasks. Compared to previous in-memory computing system, this work provides over 85 times improvement in energy efficiency with an approximately 340 times reduction in hardware overhead. This work can pave the road toward a highly efficient in-memory computing platform for high-performance computing.
A molecular optomechanics approach reveals functional relevance of force transduction across talin and desmoplakin
Authors: Sadhanasatish Tanmay , Augustin Katharina , Windgasse Lukas , Chrostek-Grashoff Anna , Rief Matthias , Grashoff Carsten
Published: June 2023

Many mechanobiological processes that govern development and tissue homeostasis are regulated on the level of individual molecular linkages, and a number of proteins experiencing piconewton-scale forces in cells have been identified. However, under which conditions these force-bearing linkages become critical for a given mechanobiological process is often still unclear. Here, we established an approach to revealing the mechanical function of intracellular molecules using molecular optomechanics. When applied to the integrin activator talin, the technique provides direct evidence that its role as a mechanical linker is indispensable for the maintenance of cell-matrix adhesions and overall cell integrity. Applying the technique to desmoplakin shows that mechanical engagement of desmosomes to intermediate filaments is expendable under homeostatic conditions yet strictly required for preserving cell-cell adhesion under stress. These results reveal a central role of talin and desmoplakin as mechanical linkers in cell adhesion structures and demonstrate that molecular optomechanics is a powerful tool to investigate the molecular details of mechanobiological processes.
A reusable, impurity-tolerant and noble metal–free catalyst for hydrocracking of waste polyolefins
Authors: Qiu Zetian , Lin Siyu , Chen Zhuo , Chen Anqi , Zhou Yitian , Cao Xudong , Wang Yu , Lin Bo-Lin
Published: June 2023

One-step conversion of low-purity polyolefins to value-added products without pretreatments represents a great opportunity for chemical recycling of waste plastics. However, additives, contaminants, and heteroatom-linking polymers tend to be incompatible with catalysts that break down polyolefins. Here, we disclose a reusable, noble metal–free and impurity-tolerant bifunctional catalyst, MoS

x

-Hbeta, for hydroconversion of polyolefins into branched liquid alkanes under mild conditions. The catalyst works for a wide scope of polyolefins, including different kinds of high–molecular weight polyolefins, polyolefins mixed with various heteroatom-linking polymers, contaminated polyolefins, and postconsumer polyolefins with/without cleaning under 250°C and 20 to 30 bar H
2
in 6 to 12 hours. A 96% yield of small alkanes was successfully achieved even at a temperature as low as 180°C. These results demonstrate the great potentials of hydroconversion in practical use of waste plastics as a largely untapped carbon feedstock.
Accelerating drug target inhibitor discovery with a deep generative foundation model
Authors: Chenthamarakshan Vijil , Hoffman Samuel C. , Owen C. David , Lukacik Petra , Strain-Damerell Claire , Fearon Daren , Malla Tika R. , Tumber Anthony , Schofield Christopher J. , Duyvesteyn Helen M.E. , Dejnirattisai Wanwisa , Carrique Loic , Walter Thomas S. , Screaton Gavin R. , Matviiuk Tetiana , Mojsilovic Aleksandra , Crain Jason , Walsh Martin A. , Stuart David I. , Das Payel
Published: June 2023

Inhibitor discovery for emerging drug-target proteins is challenging, especially when target structure or active molecules are unknown. Here, we experimentally validate the broad utility of a deep generative framework trained at-scale on protein sequences, small molecules, and their mutual interactions—unbiased toward any specific target. We performed a protein sequence-conditioned sampling on the generative foundation model to design small-molecule inhibitors for two dissimilar targets: the spike protein receptor-binding domain (RBD) and the main protease from SARS-CoV-2. Despite using only the target sequence information during the model inference, micromolar-level inhibition was observed in vitro for two candidates out of four synthesized for each target. The most potent spike RBD inhibitor exhibited activity against several variants in live virus neutralization assays. These results establish that a single, broadly deployable generative foundation model for accelerated inhibitor discovery is effective and efficient, even in the absence of target structure or binder information.
Intrinsically stretchable three primary light-emitting films enabled by elastomer blend for polymer light-emitting diodes
Authors: Jeong Min Woo , Ma Jin Hyun , Shin Jae Seung , Kim Jun Su , Ma Guorong , Nam Tae Uk , Gu Xiaodan , Kang Seong Jun , Oh Jin Young
Published: June 2023

Intrinsically stretchable light-emitting materials are crucial for skin-like wearable displays; however, their color range has been limited to green-like yellow lights owing to the restricted stretchable light-emitting materials (super yellow series materials). To develop skin-like full-color displays, three intrinsically stretchable primary light-emitting materials [red, green, and blue (RGB)] are essential. In this study, we report three highly stretchable primary light-emitting films made from a polymer blend of conventional RGB light-emitting polymers and a nonpolar elastomer. The blend films consist of multidimensional nanodomains of light-emitting polymers that are interconnected in an elastomer matrix for efficient light-emitting under strain. The RGB blend films exhibited over 1000 cd/m
2
luminance with low turn-on voltage (<5
V
on
) and the selectively stretched blend films on rigid substrate maintained stable light-emitting performance up to 100% strain even after 1000 multiple stretching cycles.
A compact DEA-based soft peristaltic pump for power and control of fluidic robots
Authors: Xu Siyi , Nunez Cara M. , Souri Mohammad , Wood Robert J.
Published: June 2023

Fluid-driven robotic systems typically use bulky and rigid power supplies, considerably limiting their mobility and flexibility. Although various forms of low-profile soft pumps have been demonstrated, they either are limited to specific working fluids or generate limited flow rates or pressures, making them ill-suited for widespread robotics applications. In this work, we introduce a class of centimeter-scale soft peristaltic pumps for power and control of fluidic robots. An array of high power density robust dielectric elastomer actuators (DEAs) (each weighing 1.7 grams) were adopted as soft motors, operated in a programmed pattern to produce pressure waves in a fluidic channel. We investigated and optimized the dynamic performance of the pump by analyzing the interaction between the DEAs and the fluidic channel with a fluid-structure interaction finite element model. Our soft pump achieved a maximum blocked pressure of 12.5 kilopascals and a run-out flow rate of 39 milliliters per minute with a response time of less than 0.1 second. The pump can generate bidirectional flow and adjustable pressure through control of drive parameters such as voltage and phase shift. Furthermore, the use of peristalsis makes the pump compatible with various liquids. To illustrate the versatility of the pump, we demonstrate mixing a cocktail, powering custom actuators for haptic devices, and performing closed-loop control of a soft fluidic actuator. This compact soft peristaltic pump opens up possibilities for future on-board power sources for fluid-driven robots in a variety of applications, including food handling, manufacturing, and biomedical therapeutics.
High-resolution daily profiles of tissue adrenal steroids by portable automated collection
Authors: Upton Thomas J. , Zavala Eder , Methlie Paal , Kämpe Olle , Tsagarakis Stylianos , Øksnes Marianne , Bensing Sophie , Vassiliadi Dimitra A. , Grytaas Marianne A. , Botusan Ileana R. , Ueland Grethe , Berinder Katarina , Simunkova Katerina , Balomenaki Maria , Margaritopoulos Dimitris , Henne Nina , Crossley Robin , Russell Georgina , Husebye Eystein S. , Lightman Stafford L.
Published: June 2023

Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of the disease. Because adrenal hormones are secreted with both circadian and ultradian periods, conventional single–time point measurements provide limited information about rhythmicity and, crucially, do not provide information during sleep, when many hormones fluctuate from nadir to peak concentrations. If blood sampling is attempted overnight, then this necessitates admission to a clinical research unit, can be stressful, and disturbs sleep. To overcome this problem and to measure free hormones within their target tissues, we used microdialysis, an ambulatory fraction collector, and liquid chromatography–tandem mass spectrometry to obtain high-resolution profiles of tissue adrenal steroids over 24 hours in 214 healthy volunteers. For validation, we compared tissue against plasma measurements in a further seven healthy volunteers. Sample collection from subcutaneous tissue was safe, well tolerated, and allowed most normal activities to continue. In addition to cortisol, we identified daily and ultradian variation in free cortisone, corticosterone, 18-hydroxycortisol, aldosterone, tetrahydrocortisol and allo-tetrahydrocortisol, and the presence of dehydroepiandrosterone sulfate. We used mathematical and computational methods to quantify the interindividual variability of hormones at different times of the day and develop “dynamic markers” of normality in healthy individuals stratified by sex, age, and body mass index. Our results provide insight into the dynamics of adrenal steroids in tissue in real-world settings and may serve as a normative reference for biomarkers of endocrine disorders (ULTRADIAN, NCT02934399).
Efficacy of oseltamivir treatment in influenza virus-infected obese mice
Authors: Honce Rebekah , Jones Jeremy , Meliopoulos Victoria A. , Livingston Brandi , Sharp Bridgett , Estrada Leonardo D. , Wang Lindsey , Caulfield William , Freeman Burgess , Govorkova Elena , Schultz-Cherry Stacey
Published: June 2023

Obesity has been epidemiologically and empirically linked with more severe diseases upon influenza infection. To ameliorate severe disease, treatment with antivirals, such as the neuraminidase inhibitor oseltamivir, is suggested to begin within days of infection especially in high-risk hosts. However, this treatment can be poorly effective and may generate resistance variants within the treated host. Here, we hypothesized that obesity would reduce oseltamivir treatment effectiveness in the genetically obese mouse model. We demonstrated that oseltamivir treatment does not improve viral clearance in obese mice. While no traditional variants associated with oseltamivir resistance emerged, we did note that drug treatment failed to quench the viral population and did lead to phenotypic drug resistance
in vitro
. Together, these studies suggest that the unique pathogenesis and immune responses in obese mice could have implications for pharmaceutical interventions and the within-host dynamics of the influenza virus population.

IMPORTANCE

Influenza virus infections, while typically resolving within days to weeks, can turn critical, especially in high-risk populations. Prompt antiviral administration is crucial to mitigating these severe sequalae, yet concerns remain if antiviral treatment is effective in hosts with obesity. Here, we show that oseltamivir does not improve viral clearance in genetically obese or type I interferon receptor-deficient mice. This suggests a blunted immune response may impair oseltamivir efficacy and render a host more susceptible to severe disease. This study furthers our understanding of oseltamivir treatment dynamics both systemically and in the lungs of obese mice, as well as the consequences of oseltamivir treatment for the within-host emergence of drug-resistant variants.
Salmonella enterica
serovar Typhi uses two type 3 secretion systems to replicate in human macrophages and colonize humanized mice
Authors: Hamblin Meagan , Schade Ruth , Narasimhan Ramya , Monack Denise M.
Published: June 2023

Salmonella enterica
serovar Typhi (
S
. Typhi) is a human-restricted pathogen that replicates in macrophages. In this study, we investigated the roles of the
S
. Typhi type 3 secretion systems (T3SSs) encoded on
Salmonella
pathogenicity islands (SPI)-1 (T3SS-1) and SPI-2 (T3SS-2) during human macrophage infection. We found that mutants of
S
. Typhi deficient for both T3SSs were defective for intramacrophage replication as measured by flow cytometry, viable bacterial counts, and live time-lapse microscopy. T3SS-secreted proteins PipB2 and SifA contributed to
S
. Typhi replication and were translocated into the cytosol of human macrophages through both T3SS-1 and T3SS-2, demonstrating functional redundancy for these secretion systems. Importantly, an
S
. Typhi mutant strain that is deficient for both T3SS-1 and T3SS-2 was severely attenuated in the ability to colonize systemic tissues in a humanized mouse model of typhoid fever. Overall, this study establishes a critical role for
S
. Typhi T3SSs during its replication within human macrophages and during systemic infection of humanized mice.

IMPORTANCE

Salmonella enterica
serovar Typhi is a human-restricted pathogen that causes typhoid fever. Understanding the key virulence mechanisms that facilitate
S
. Typhi replication in human phagocytes will enable rational vaccine and antibiotic development to limit the spread of this pathogen. While
S
. Typhimurium replication in murine models has been studied extensively, there is limited information available about
S
. Typhi replication in human macrophages, some of which directly conflict with findings from
S
. Typhimurium murine models. This study establishes that both of
S
. Typhi’s two type 3 secretion systems (T3SS-1 and T3SS-2) contribute to intramacrophage replication and virulence.
Differential dysregulation of β-TrCP1 and -2 by HIV-1 Vpu leads to inhibition of canonical and non-canonical NF-κB pathways in infected cells
Authors: Pickering Suzanne , Sumner Jonathan , Kerridge Claire , Perera Marianne , Neil Stuart
Published: June 2023

The HIV-1 Vpu protein is expressed late in the virus lifecycle to promote infectious virus production and avoid innate and adaptive immunity. This includes the inhibition of the NF-κB pathway which, when activated, leads to the induction of inflammatory responses and the promotion of antiviral immunity. Here we demonstrate that Vpu can inhibit both canonical and non-canonical NF-κB pathways, through the direct inhibition of the F-box protein β-TrCP, the substrate recognition portion of the Skp1-Cul1-F-box (SCF)
β-TrCP
ubiquitin ligase complex. There are two paralogues of β-TrCP (β-TrCP1/BTRC and β-TrCP2/FBXW11), encoded on different chromosomes, which appear to be functionally redundant. Vpu, however, is one of the few β-TrCP substrates to differentiate between the two paralogues. We have found that patient-derived alleles of Vpu, unlike those from lab-adapted viruses, trigger the degradation of β-TrCP1 while co-opting its paralogue β-TrCP2 for the degradation of cellular targets of Vpu, such as CD4. The potency of this dual inhibition correlates with stabilization of the classical IκBα and the phosphorylated precursors of the mature DNA-binding subunits of canonical and non-canonical NF-κB pathways, p105/NFκB1 and p100/NFκB2, in HIV-1 infected CD4
+
T cells. Both precursors act as alternative IκBs in their own right, thus reinforcing NF-κB inhibition at steady state and upon activation with either selective canonical or non-canonical NF-κB stimuli. These data reveal the complex regulation of NF-κB late in the viral replication cycle, with consequences for both the pathogenesis of HIV/AIDS and the use of NF-κB-modulating drugs in HIV cure strategies.

IMPORTANCE

The NF-κB pathway regulates host responses to infection and is a common target of viral antagonism. The HIV-1 Vpu protein inhibits NF-κB signaling late in the virus lifecycle, by binding and inhibiting β-TrCP, the substrate recognition portion of the ubiquitin ligase responsible for inducing IκB degradation. Here we demonstrate that Vpu simultaneously inhibits and exploits the two different paralogues of β-TrCP by triggering the degradation of β-TrCP1 and co-opting β-TrCP2 for the destruction of its cellular targets. In so doing, it has a potent inhibitory effect on both the canonical and non-canonical NF-κB pathways. This effect has been underestimated in previous mechanistic studies due to the use of Vpu proteins from lab-adapted viruses. Our findings reveal previously unappreciated differences in the β-TrCP paralogues, revealing functional insights into the regulation of these proteins. This study also raises important implications for the role of NF-κB inhibition in the immunopathogenesis of HIV/AIDS and the way that this may impact on HIV latency reversal strategies based on the activation of the non-canonical NF-κB pathway.
Complete Genome Sequence of
Polynucleobacter
sp. Strain TUM22923, Isolated from Antarctic Lake Sediment
Authors: Shimada Sho , Nakai Ryosuke , Aoki Kotaro , Miura Shota , Komori Kohji , Kudoh Sakae , Imura Satoshi , Ishii Yoshikazu , Tateda Kazuhiro
Published: June 2023

Here, we report the complete genome sequence of
Polynucleobacter
sp. strain TUM22923, isolated from Antarctic lake sediment. This strain has a genome of 1,860,127 bp, comprising 1,848 protein-coding sequences. These sequence data could contribute to the elucidation of genome streamlining and low-temperature adaptation in members of
Polynucleobacter
, a cosmopolitan group of ultramicrobacteria.
Sphingopyxis
Species Isolated from Sand Filter Biofilm at an Australian Drinking Water Treatment Works
Authors: Smith Holly-Anne B. , Mullins Alex J. , Webster Gordon , Sapsford Devin , Gaskin Paul , Monis Paul T. , Hoefel Daniel , Saint Christopher P. , Weightman Andrew J.
Published: June 2023

Three strains isolated by geosmin enrichment from a sand filter in an Australian drinking water treatment works were genome sequenced to identify their taxonomic placement, and a bench-scale batch experiment confirmed their geosmin-degrading capability. Using the average nucleotide identity based on the MUMmer algorithm (ANIm), pairwise digital DNA-DNA hybridization (dDDH), and phylogenomic analyses, the strains were identified as
Sphingopyxis
species.
Draft Genome Sequence of Neopoerus faecalis gen. nov., sp. nov., an
Oscillospiraceae
Strain Isolated from Human Feces
Authors: Selma-Royo Marta , Ricci Liviana , Golzato Davide , Servais Charlotte , Armanini Federica , Asnicar Francesco , Pinto Federica , Segata Nicola
Published: June 2023

Here, we report the isolation and genome assembly of a strictly anaerobic bacterium from a previously uncharacterized species in the
Oscillospiraceae
family, isolated from a fecal sample from a healthy adult human. The name
Neopoerus faecalis
gen. nov., sp. nov. is proposed.
Insights into the metabolic specificities of pathogenic strains from the
Ralstonia solanacearum
species complex
Authors: Baroukh Caroline , Cottret Ludovic , Pires Emma , Peyraud Rémi , Guidot Alice , Genin Stéphane
Published: June 2023

All the strains grouped under the species
Ralstonia solanacearum
represent a species complex responsible for many diseases on agricultural crops throughout the world. The strains have different lifestyles and host range. Here, we investigated whether specific metabolic pathways contribute to strain diversification. To this end, we carried out systematic comparisons on 11 strains representing the diversity of the species complex. We reconstructed the metabolic network of each strain from its genome sequence and looked for the metabolic pathways differentiating the different reconstructed networks and, by extension, the different strains. Finally, we conducted an experimental validation by determining the metabolic profile of each strain with the Biolog technology. Results revealed that the metabolism is conserved between strains, with a core metabolism composed of 82% of the pan-reactome. The three species composing the species complex could be distinguished according to the presence/absence of some metabolic pathways, in particular, one involving salicylic acid degradation. Phenotypic assays revealed that the trophic preferences on organic acids and several amino acids such as glutamine, glutamate, aspartate, and asparagine are conserved between strains. Finally, we generated mutants lacking the quorum-sensing-dependent regulator PhcA in four diverse strains, and we showed that the
phcA-
dependent trade-off between growth and production of virulence factors is conserved across the
R. solanacearum
species complex.

IMPORTANCE

Ralstonia solanacearum
is one of the most important threats to plant health worldwide, causing disease on a very large range of agricultural crops such as tomato or potato. Behind the
R. solanacearum
name are hundreds of strains with different host range and lifestyle, classified into three species. Studying the differences between strains allows to better apprehend the biology of the pathogens and the specificity of some strains. None of the published genomic comparative studies have focused on the metabolism of the strains so far. We developed a new bioinformatic pipeline to build high-quality metabolic networks and used a combination of metabolic modeling and high-throughput phenotypic Biolog microplates to look for the metabolic differences between 11 strains across the three species. Our study revealed that genes encoding enzymes are overall conserved, with few variations between strains. However, more variations were observed when considering substrate usage. These variations probably result from regulation rather than the presence or absence of enzymes in the genome.
Type IV Pilus-Mediated Inhibition of
Acinetobacter baumannii
Biofilm Formation by Phenothiazine Compounds
Authors: Vo Nam , Sidner Benjamin S. , Yu Yafan , Piepenbrink Kurt H.
Published: June 2023

Acinetobacter
infections are a growing burden on health care systems worldwide due to increasing antimicrobial resistance through multiple mechanisms. Biofilm formation is an established mechanism of antimicrobial resistance, and its inhibition has the potential to potentiate the use of existing drugs against pathogenic
Acinetobacter
.
Epidemiology of Methicillin-Resistant Staphylococcus aureus in Slovakia, 2020 – Emergence of an Epidemic USA300 Clone in Community and Hospitals
Authors: Tkadlec Jan , Le Anh Vu , Brajerova Marie , Soltesova Anna , Marcisin Jozef , Drevinek Pavel , Krutova Marcela
Published: June 2023

The epidemiology of MRSA is characterized by the rise and fall of epidemic clones. Understanding the spread, as well as the evolution of successful MRSA clones, depends on the knowledge of global MRSA epidemiology.
Interactome Analysis Identifies MSMEI_3879 as a Substrate of Mycolicibacterium smegmatis ClpC1
Authors: Ogbonna Emmanuel C. , Anderson Henry R. , Beardslee Patrick C. , Bheemreddy Priyanka , Schmitz Karl R.
Published: June 2023

Drug-resistant tuberculosis infections are a major challenge to global public health. Much effort has been invested in identifying new drug targets in the causative pathogen,
Mycobacterium tuberculosis
.
Persistent mortality and heart failure burden of anterior ST-segment elevation myocardial infarction following primary percutaneous coronary intervention: real-world evidence from the US Medicare Data Set
Authors: Martin Jack
Published: June 2023

Objectives

We sought to compare the temporal trends in the incidence of death and rehospitalisation for congestive heart failure (CHF) following anterior ST-elevation myocardial infarction (STEMI) in a Medicare cohort of beneficiaries treated with primary percutaneous coronary intervention (PCI) in 2005 (n=1479) with those treated in 2016 through quarter (Q) 2 of 2017 (n=22 432).

Design

This retrospective analysis examined outcomes using both descriptive and regression analysis to control for differences in patient clinical characteristics over time.

Primary outcome measures

The primary outcomes are 1 year and 2 year rates of mortality and re-hospitalisation for CHF.

Results

The 1 year mortality rate was numerically higher in the 2016 cohort at 10.3% (95% CI 9.9 to 10.7) versus 8.9% (CI 7.4 to 10.3; p=0.068). The 2 year mortality rate was significantly higher in the 2016 cohort at 14.5% (CI 13.9 to 15.1) versus 11.4% (CI 9.2 to 13.6; p<0.01). The 1 year rehospitalisation for CHF was lower in the 2016 cohort at 10.6% (CI 10.0 to 11.2) versus 16.7% (CI 14.0 to 19.4; p<0.001), but the 2 year rate was not significantly different at 19.3% (CI 17.7 to 20.9) versus 20.7% (CI 16.4 to 24.9; p=0.55). After adjustment for covariates with two models, the 1 year mortality increased by 2.3% (CI 0.8 to 3.7; p<0.01) and 4.1% (CI 2.6 to 5.6; p<0.001) in the 2016 cohort. The 2 year adjusted mortality also increased by 4.2% (CI 2.0 to 6.4; p<0.001) and 6.5% (CI 4.2 to 8.7; p<0.001) in the 2016 cohort. The risk adjusted trends for rehospitalisation for CHF were similar to the unadjusted findings.

Conclusions

Despite prior improvements in STEMI outcomes in the reperfusion era related to the broad adoption of timely PCI, there is a persistent high mortality and CHF burden in Medicare beneficiaries with anterior STEMI. New strategies that address reperfusion injury and enhance myocardial salvage are needed.
Spontaneous spinal cord infarctions: a systematic review and pooled analysis protocol
Authors: El-Hajj Victor Gabriel , Stenimahitis Vasilios , Gharios Maria , Mahdi Omar Ali , Elmi-Terander Adrian , Edström Erik
Published: June 2023

Introduction

Spinal cord infarction (SCInf) is a rare ischaemic event that manifests with acute neurological deficits. It is typically classified as either spontaneous, defined as SCInf without any inciting event, or periprocedural, which typically occur in conjunction with vascular surgery with aortic manipulations. While periprocedural SCInf has recently been the subject of intensified research, especially focusing on the primary prevention of this complication, spontaneous SCInf remains less studied.

Methods and analysis

Electronic databases, including PubMed, Web of Science and Embase, will be searched using the keywords “spinal cord”, “infarction”, “ischemia” and “spontaneous”. The search will be set to provide only English studies published from database inception. Editorials, letters and reviews will also be excluded. Reference lists of relevant records will also be searched. Identified studies will be screened for inclusion, by one reviewer in the first step and then three in the next step to decrease the risk of bias. The synthesis will address several topics of interest including epidemiology, presentation, diagnostics, treatment strategies, outcomes and predictors. The review aims to gather the body of evidence to summarise the current knowledge on SCInf. This will lead to a better understanding of the condition, its risk factors, diagnosis and management. Moreover, the review will also provide an understanding of the prognosis of patients with SCInf with respect to neurological function, quality of life and mortality. Finally, this overview of the literature will allow the identification of knowledge gaps to help guide future research efforts.

Ethics and dissemination

Ethics approval was not required for our review as it is based on existing publications. The final manuscript will be submitted to a peer-reviewed journal.
Integrating shared decision-making, expressing preferences and active participation of older adults in primary care nursing: a systematic review of qualitative studies and qualitative meta-synthesis
Authors: Martínez-Angulo Pablo , Rich-Ruiz Manuel , Ventura-Puertos Pedro E , López-Quero Salvador
Published: June 2023

Objectives

To systematically synthesise the results of primary qualitative studies on how community-dwelling older adults experience shared decision-making processes, express preferences and actively participate in care.

Design

Systematic review of qualitative studies and qualitative meta-synthesis.

Methods

We focused on studies about community-dwelling participants aged ≥65 undergoing a health-disease process circumscribed to a primary healthcare setting, and the central theme should focus on either shared decision-making, expressing preferences or patient participation. We searched the following databases: MEDLINE, CINAHL, Web of Science, Scopus and PsycINFO (time publication frame 2012–2022). We excluded studies in those cases where the qualitative results were not analysed or unrelated to the phenomenon addressed, phenomena were not clear enough to be included or the setting did not occur in the community.

Results

A total of 12 studies were included in this meta-synthesis. We appraised the quality of the selected studies through Critical Appraisal Skills Programme (CASP) Checklist. The metasummary comprised the frequency and intensity of qualitative patterns across the included studies. The meta-synthesis revealed four influential elements in their interaction: recognising personal qualities, facing professional characteristics, experiences of discrimination and a double-edged context.

Conclusions

The phenomena studied were influenced by how older people approached their role in their binomial relationship with healthcare professionals. Those with a reinforced self-concept were better aware of health-disease-related situations regarding shared decision-making and the importance of being communicatively assertive. Professional characteristics were also crucial in how older people modulated their acting ability through their personality, communication skills and the approach healthcare professionals used towards older adults. Situations of discrimination generated through an imbalance of power inhibited the expression of preferences and hindered the active participation of older people. The context surrounding the participants influenced all these situations, key in tipping the balance between a therapeutic and a harmful side.

PROSPERO registration number

CRD42022363515.
Occupational respiratory morbidity and associated factors among hairdressers in Ethiopia: a cross-sectional study
Authors: Tesfaye Amensisa Hailu , Engdaw Garedew Tadege , Desye Belay , Abere Giziew
Published: June 2023

Objective

This study was designed to determine the prevalence and factors associated with occupational respiratory morbidity among hairdressers in Northwestern Ethiopia.

Design

A cross-sectional study was conducted from 6 July 2022 to 17 August 2022. The data were collected using a standardised American Thoracic Society questionnaire. The collected data were entered into EpiData V.4.6 and analysed using Stata V.14. A multivariable logistic regression analysis was conducted to identify factors associated with occupational respiratory morbidity. The association was determined using an adjusted OR (AOR) with a 95% CI at a p value of <0.05.

Setting

The study was conducted in Gondar city, Northwestern Ethiopia.

Participants

A total of 403 hairdressers participated in this study.

Outcome measures

The primary outcome is the prevalence of occupational respiratory morbidity.

Results

The total response rate was 95.5%. The majority, 250 (62%) of the respondents were women. The mean age (±SD) of the respondents was 27 (±6.0) years. The overall prevalence of occupational respiratory morbidity during the past 12 months was found to be 134 (33.3%) (95% CI (28.7% to 38.1%)). Female hairdressers (18.6%) showed greater respiratory morbidity than male hairdressers (14.7%). Working experience 3–5 years (AOR: 3.05; 95% CI (1.76 to 5.30)) and working experience >5 years (AOR: 6.22; 95% CI (2.73 to 14.16)), overweight (body mass index (BMI)) (AOR: 3.01; 95% CI (1.19 to 7.58)) and working near roadsides (AOR: 2.15; 95% CI (1.33 to 3.37)) were risk factors of occupational respiratory morbidity among hairdressers.

Conclusions

This study concluded that one-third of hairdressers experienced occupational respiratory morbidity. Longer work experience, higher BMI and working near roadsides were identified as significant risk factors for respiratory morbidity in hairdressers. Dietary calorie restrictions for overweight individuals and the development and implementation of air pollution mitigation measures targeted at roadside workers are advised to curb the problem.
Impact of a quality improvement programme on the preparation and administration of medications via a nasoenteral feeding tube: 2014–2019 intervention study
Authors: Pereira Rosana Aparecida , Bonacim Carlos Alberto Grespan , da Costa Laís Rosa Moreno , Rigobello Mayara Carvalho Godinho , de Souza Fabiana Bolela , Grande Marcia Mazzeo , Gimenes Fernanda Raphael Escobar
Published: June 2023

Aims

Evaluate the impact of a quality improvement programme on the reduction of feeding tube obstruction frequencies, analyse the predictive variables of this safety incident, and estimate the economic costs related to the quality improvement programme during the period from 2014 to 2019.

Methods

Plan–Do–Study–Act cycles were performed to test the changes in drug preparation and administration processes via a nasoenteral feeding tube and to evaluate the outcome, process and balance measures. Statistical control charts were elaborated, and the bottom-up direct costing methodology was used to estimate the costs of the improvement programme. The impact of the programme on the monitoring measures was evaluated using logistic regression analysis.

Interventions

The following changes were tested in the hospital participating in the study: acquisition of the Easy Crush equipment for tablet crushing, use of appropriate packaging to crush hard tablets, standardise procedures for scheduling administration times and/or substitution of the pharmaceutical form, educational activities for the nursing team and elaboration and availability of infographics for the nursing team, patients and/or family/caregivers.

Results

There was a significant improvement in the frequency of tube obstructions, from 41.1% in 2014 to 57.9% in 2015–2017 and 9.6% in 2018–2019 (p=0.0010). After the execution of the improvement programme, it was estimated that the cost of dose preparation was reduced from R$1067.50 in 2014 to R$719.80 in 2015–2017 and R$433.10 in 2015–2019.

Conclusion

By re-establishing the processes of drug preparation and administration via a nasoenteral feeding tube, through the acquisition of appropriate equipment for crushing hard tablets, together with educational activities for the nursing team, we could observe a reduction in tube obstructions and the cost of processes.
Development of an algorithm-based approach using neuromuscular test results to indicate an increased risk for non-contact lower limb injuries in elite football players
Authors: Wagemans Jente , De Leeuw Arie-Willem , Catteeuw Peter , Vissers Dirk
Published: June 2023

Objectives

This retrospective cohort study explored an algorithm-based approach using neuromuscular test results to indicate an increased risk for non-contact lower limb injuries in elite football players.

Methods

Neuromuscular data (eccentric hamstring strength, isometric adduction and abduction strength and countermovement jump) of 77 professional male football players were assessed at the start of the season (baseline) and, respectively, at 4, 3, 2 and 1 weeks before the injury. We included 278 cases (92 injuries; 186 healthy) and applied a subgroup discovery algorithm.

Results

More injuries occurred when between-limb abduction imbalance 3 weeks before injury neared or exceeded baseline values (threshold≥0.97), or adduction muscle strength of the right leg 1 week before injury remained the same or decreased compared with baseline values (threshold≤1.01). Moreover, in 50% of the cases, an injury occurred if abduction strength imbalance before the injury is over 97% of the baseline values and peak landing force in the left leg 4 weeks before the injury is lower than 124% compared with baseline.

Conclusions

This exploratory analysis provides a proof of concept demonstrating that a subgroup discovery algorithm using neuromuscular tests has potential use for injury prevention in football.
Utility of the New Early Warning Score (NEWS) in combination with the neutrophil–lymphocyte ratio for the prediction of prognosis in older patients with pneumonia
Authors: Kakehi Eiichi , Uehira Ryo , Ohara Nobuaki , Akamatsu Yukinobu , Osaka Taeko , Sakurai Shigehisa , Hirotani Akane , Nozaki Takafumi , Shoji Keisuke , Adachi Seiji , Kotani Kazuhiko
Published: June 2023

Objective

Predictors of prognosis are necessary for use in routine clinical practice for older patients with pneumonia, given the ageing of the population. Recently, the National Early Warning Score (NEWS), a comprehensive predictor of severity that consists solely of physiological indicators, has been proposed to predict the prognosis of pneumonia. The neutrophil/lymphocyte ratio (NLR) is a simple index of inflammation that may also be predictive of pneumonia. In the present study, we aimed to determine whether NEWS or a combination of NEWS and NLR predicts mortality in older patients with pneumonia.

Design

A retrospective cohort study.

Setting

A general hospital in Japan.

Participants

We collected data from patients aged ≥65 years with pneumonia who were admitted between 2018 and 2020 (n=282; age=85.3 (7.9)). Data regarding vital signs, demographics and the length of hospital stay, in addition to the NEWS and NLR, were extracted from the participants’ electronic medical records.

Intervention

The utility of the combination of NEWS and NLR was assessed using NEWS×NLR and NEWS+NLR.

Main outcome measures

Their predictive ability for 30-day mortality as the primary outcome was assessed using receiver operating characteristic (ROC) curve analysis.

Results

According to the NEWS classification, 80 (28.3%), 64 (22.7%) and 138 (48.9%) of the participants were at low, medium and high risk of mortality, respectively. The 30-day mortality for the entire cohort was 9.2% (n=26), and the mortality rate increased with the NEWS classification: low, 1.3%; medium, 7.8%; and high, 14.5%. The NLRs were 6.0 (4.2–9.8), 6.8 (4.8–10.4) and 14.6 (9.4–22.2), respectively (p<0.001). The areas under the ROC curves for 30-day mortality were 0.73 for the NEWS score, 0.84 for NEWS×NLR and 0.83 for NEWS+NLR, indicating that the combinations represent superior predictors of mortality to the NEWS alone. NEWS×NLR and NEWS+NLR tended to have better sensitivity, accuracy, positive predictive value and negative predictive value than NEWS alone (p=0.06).

Conclusions

A combination of the NEWS and NLR (NEWS×NLR or NEWS+NLR) may be superior to the NEWS alone for the prediction of 30-day mortality in older patients with pneumonia. However, further validation of these combinations for use in the prediction of prognosis is required.
Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression
Authors: Lan Xiaofeng , Wang Chengyu , Zhang Fan , Liu Haiyan , Fu Ling , Li Weicheng , Ye Yanxiang , Hu Zhibo , Mai Siming , Ning Yuping , Zhou Yanling
Published: June 2023

Background

Patients with anxious major depressive disorder (MDD) are more likely to have poorer outcomes than those with non-anxious MDD. However, the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.

Aims

We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation, both anxious and non-anxious.

Methods

Fifty-four adolescents with anxious (n=33) and non-anxious (n=21) MDD received three infusions of esketamine 0.25 mg/kg or active-placebo (midazolam 0.045 mg/kg) over 5 days, with routine inpatient care and treatment. Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion (day 6, primacy efficacy endpoint) and throughout the 4-week post-treatment (days 12, 19 and 33).

Results

In subjects who received esketamine, a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6 (72.7% vs 18.8%, p=0.015) and day 12 (90.9% vs 43.8%, p=0.013), and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33 (72.7% vs 26.7%, p=0.045). No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.

Conclusions

Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD; however, this benefit was temporary and was not maintained over time.

Trial registration number

ChiCTR2000041232.
Clinically significant myocardial bridging
Authors: Danek Barbara A , Kearney Kathleen , Steinberg Zachary L
Published: June 2023

Myocardial bridging is a common anatomical variant in which a major epicardial coronary artery takes an intramyocardial course, leading to dynamic systolic compression. Because coronary perfusion occurs primarily during diastole, most patients with this anatomical variant have no associated perfusion abnormalities or symptoms. Despite this, there is a subset of patients with myocardial bridging who experience ischaemic symptoms. Determining which anatomical variants are benign and which are clinically relevant remains a challenge. Further complicating the picture, functional factors such as diastolic dysfunction and coronary vasospasm may exacerbate myocardial bridging-related ischaemia. In patients with ischaemic symptoms in the absence of alternative explanations, a detailed assessment of myocardial bridging with invasive physiology should be performed to define the significance of the lesion and guide tailored medical therapy. Patients with refractory symptoms despite maximally tolerated medical therapy should be considered for surgical coronary unroofing.
G-CSF rescue of FOLFIRINOX-induced neutropenia leads to systemic immune suppression in mice and humans
Authors: Cardot-Ruffino Victoire , Bollenrucher Naima , Delius Luisa , Wang S Jennifer , Brais Lauren K , Remland Joshua , Keheler C Elizabeth , Sullivan Keri M , Abrams Thomas A , Biller Leah H , Enzinger Peter C , McCleary Nadine J , Patel Anuj K , Rubinson Douglas A , Schlechter Benjamin , Slater Sarah , Yurgelun Matthew B , Cleary James M , Perez Kimberly , Dougan Michael , Ng Kimmie , Wolpin Brian M , Singh Harshabad , Dougan Stephanie K
Published: June 2023

Background

Recombinant granulocyte colony-stimulating factor (G-CSF) is routinely administered for prophylaxis or treatment of chemotherapy-induced neutropenia. Chronic myelopoiesis and granulopoiesis in patients with cancer has been shown to induce immature monocytes and neutrophils that contribute to both systemic and local immunosuppression in the tumor microenvironment. The effect of recombinant G-CSF (pegfilgrastim or filgrastim) on the production of myeloid-derived suppressive cells is unknown. Here we examined patients with pancreatic cancer, a disease known to induce myeloid-derived suppressor cells (MDSCs), and for which pegfilgrastim is routinely administered concurrently with FOLFIRINOX but not with gemcitabine-based chemotherapy regimens.

Methods

Serial blood was collected from patients with pancreatic ductal adenocarcinoma newly starting on FOLFIRINOX or gemcitabine/n(ab)paclitaxel combination chemotherapy regimens. Neutrophil and monocyte frequencies were determined by flow cytometry from whole blood and peripheral blood mononuclear cell fractions. Serum cytokines were evaluated pretreatment and on-treatment. Patient serum was used in vitro to differentiate healthy donor monocytes to MDSCs as measured by downregulation of major histocompatibility complex II (HLA-DR) and the ability to suppress T-cell proliferation in vitro. C57BL/6 female mice with pancreatic tumors were treated with FOLFIRINOX with or without recombinant G-CSF to directly assess the role of G-CSF on induction of immunosuppressive neutrophils.

Results

Patients receiving FOLFIRINOX with pegfilgrastim had increased serum G-CSF that correlated with an induction of granulocytic MDSCs. This increase was not observed in patients receiving gemcitabine/n(ab)paclitaxel without pegfilgrastim. Interleukin-18 also significantly increased in serum on FOLFIRINOX treatment. Patient serum could induce MDSCs as determined by in vitro functional assays, and this suppressive effect increased with on-treatment serum. Induction of MDSCs in vitro could be recapitulated by addition of recombinant G-CSF to healthy serum, indicating that G-CSF is sufficient for MDSC differentiation. In mice, neutrophils isolated from spleen of G-CSF-treated mice were significantly more capable of suppressing T-cell proliferation.

Conclusions

Pegfilgrastim use contributes to immune suppression in both humans and mice with pancreatic cancer. These results suggest that use of recombinant G-CSF as supportive care, while critically important for mitigating neutropenia, may complicate efforts to induce antitumor immunity.