bluuebunny/crossref_metadata_2025 huggingface dataset:
Printability Prediction in Projection Two-Photon Lithography via Machine Learning Based Surrogate Modeling of Photopolymerization
Authors: Pingali Rushil , Saha Sourabh K.
Published: September 2023

The two-photon lithography (TPL) direct laser writing process enables the fabrication of complex three-dimensional features with sub-micrometer resolution. While traditional TPL techniques have suffered from low throughput due to their serial writing scheme, the process has been recently parallelized through the development of the projection two photon lithography (P-TPL) process that allows printing of entire layers at once. In this work, we use machine learning-based surrogate modeling to predict the outcomes of P-TPL to > 97% of the accuracy of a physics-based reaction-diffusion finite element simulation. Training a classification neural network on data points generated from physics-based simulations allows for computationally efficient and accurate prediction of whether a set of printing conditions will result in precise and controllable polymerization and the desired printing, as opposed to no printing or runaway polymerization. We interrogate this surrogate model to investigate the parameter regimes that are promising for successful printing. We predict combinations of rate constants necessary to print for a given set of material properties, thereby generating the first printability map for the P-TPL process and allowing informed selection of photoresists and printing parameters in the future.
Effect of Multi-Axial Forging on Mechanical Properties and Microstructures of AA7075/TaC Composites
Authors: Khalkho John Samson , Karunakar D. Benny
Published: September 2023

The objective of the current work is to develop a AA7075 reinforced Tantalum Carbide (1, 3, 5, and 7 wt%) composite through stir casting. The secondary process such as Multi-axial forging (MAF) followed by ageing was performed on AA7075/5TaC(S-4) composite to enhance the strength and ductility of composite. The evolution of microstructures were examined by Optical microscope (OM) and Field emission scanning electron microscopy (FESEM) and the MAF process was analyzed by Electron back scattered diffraction (EBSD). The microstructure characterization reveals that refinement of grains take place with the addition of TaC due to the pinning effect. The microstructure of the MAF shows suppression of dynamic recovery and generation of dislocation density because of strain energy effect at room temperature. The mechanical properties were measured by Vickers hardness and universal tensile testing machine and obtained as the highest for 5 wt % TaC which is 142 Hv, 211 YS, and 254 UTS. MAF specimen shows an improvement in mechanical properties and percentage elongation compared to properties obtained in S-4 composite specimen. The highest UTS, YS, and % Elongation of S-4 specimen was achieved with MAF+aged when the cumulative strain was up to 4.8. The enhancement in hardness and tensile strength of the developed composite and MAF specimen were discussed with various strengthening mechanisms.
Transfer Learning for Predictive Quality in Laser-Induced Plasma Micro-Machining
Authors: Chen Mengfei , Malhotra Rajiv , Guo Weihong “Grace”
Published: September 2023

In laser-induced plasma micro-machining (LIPMM), a focused, ultrashort pulsed laser beam creates a highly localized plasma zone within a transparent liquid dielectric. When the beam intensity is greater than the breakdown threshold in the dielectric media, plasma is formed which is then used to ablate the workpiece. This paper aims to facilitate in-situ process monitoring and quality prediction for LIPMM by developing a deep learning model to (1) understand the relationship between acoustic emission data and quality of micro-machining with LIPMM, (2) transfer such understanding across different process parameters, and (3) predict quality accurately by fine-tuning models with a smaller dataset. Experiments and results show that the relationship learned from one process parameter can be transferred to other parameters, requiring lesser data and lesser computational time for training the model. We investigate the feasibility of transfer learning and compare the performance of various transfer learning models: different input features, different CNN structures, and the same structure with different fine-tuned layers. The findings provide insights into how to design effective transfer learning models for manufacturing applications.
Simulation and Experiment Analysis of Driveshaft
Authors: Li Jiahao , Liu Yao , Zhou Yang , Wang Youzhe , Guo Zhanling , Shen Bin
Published: September 2023

Driveshaft is a small spring coil (usually less than 1mm in diameter), made by several stainless-steel wire filaments, which transmits force and motion to the body through existing micro channels (such as arteries, veins, and gastrointestinal tract). The performance of the driveshaft determines the efficiency, stability, accuracy of force and motion transitions, the ability to pass through tortuous microchannels, and the damage to healthy tissues. In order to determine the influence of fabrication parameters (filament, wire diameter, outer diameter) on the mechanical properties (such as bending stiffness and natural frequency) of the driveshaft, a simulation was established in ABAQUS to calculate the deformation displacement under 0.0098N and first order natural frequency. The bending stiffness is calculated further. The results show that the bending stiffness and the first natural frequency of the driveshaft increase with the increase of the filament number and wire diameter. When the outer diameter of driveshaft increases, the bending stiffness increases, while the first order natural frequency decreases. In order to verify the simulation model, deformation displacement was measured in experiments. This study provides an idea for the design and selection of the driveshaft in the intervention process.
Reliability of Shoulder Helical Axes During Intransitive and Transitive Upper Limb Tasks
Authors: Adamo Paola , Temporiti Federico , Maffeis Martina , Bolzoni Francesco , Gatti Roberto
Published: September 2023

Shoulder complex stability can be estimated in vivo through the analysis of helical axes (HAs) dispersion during upper limb movements. The study aimed at investigating test–retest reliability of shoulder HAs dispersion parameters during upper limb tasks. Twenty healthy volunteers performed 2 intransitive (shoulder flexion and rotation) and one transitive (combing) tasks with the dominant and nondominant upper limbs during 2 recording sessions at 1-week distance. Kinematics was detected through an optoelectronic system. Mean distance and mean angle (MA) were adopted as HAs dispersion indexes. Reliability was excellent for mean distance (intraclass correlation coefficient [ICC]: .91) and MA (ICC: .92) during dominant flexion, and good for MA (ICC: .90) during nondominant flexion. Moderate reliability was found for HAs parameters during rotation (ICCs from .70 to .59), except for MA during dominant rotation where reliability was poor. Reliability was good for mean distance (ICC: .83) and moderate for MA (ICC: .67) during the dominant combing task, whereas no reliability was found during the nondominant combing task. HAs dispersion parameters revealed high reliability during simple intransitive tasks with the dominant limb. Reliability decreased with the increase in task complexity due to the increase in movement variability. HAs dispersion technique could be used to assess shoulder complex stability in patients after rehabilitation or surgery.
Determination of Body Composition in Community-Dwelling Older Adults With and Without Sarcopenia Using Data From Practical Measures
Authors: Amatachaya Sugalya , Chokphukiao Pakwipa , Poncumhak Puttipong , Intaruk Roongnapa , Thaweewannakij Thiwabhorn , Amatachaya Pipatana
Published: September 2023

Adequate body composition is essential for health, function, and independence in older adults. However, standard body composition assessments require complex and costly modalities, limiting their use for early detection of body composition changes and periodic follow-up. This study explored the ability of three practical measures—handgrip strength, five times sit-to-stand test, and upper limb loading during seated push-up test (ULL-SPUT)—to determine body composition in 109 older adults with and without sarcopenia. Participants (average age 76 years) were cross-sectionally measured for outcomes of the study. The ULL-SPUT and handgrip strength, but not the five times sit-to-stand test, significantly correlated with body composition (rs, r = .297–.827, p < .01). The ULL-SPUT, in combination with demographic data, could determine body composition up to 82%. Therefore, the ULL-SPUT may be a practical preliminary measure to identify older adults for whom standard body composition assessments and follow-up would prove timely and beneficial.
Cycles of fusion and fission enabled rapid parallel adaptive radiations in African cichlids
Authors: Meier Joana I. , McGee Matthew D. , Marques David A. , Mwaiko Salome , Kishe Mary , Wandera Sylvester , Neumann Dirk , Mrosso Hilary , Chapman Lauren J. , Chapman Colin A. , Kaufman Les , Taabu-Munyaho Anthony , Wagner Catherine E. , Bruggmann Rémy , Excoffier Laurent , Seehausen Ole
Published: September 2023

Although some lineages of animals and plants have made impressive adaptive radiations when provided with ecological opportunity, the propensities to radiate vary profoundly among lineages for unknown reasons. In Africa’s Lake Victoria region, one cichlid lineage radiated in every lake, with the largest radiation taking place in a lake less than 16,000 years old. We show that all of its ecological guilds evolved in situ. Cycles of lineage fusion through admixture and lineage fission through speciation characterize the history of the radiation. It was jump-started when several swamp-dwelling refugial populations, each of which were of older hybrid descent, met in the newly forming lake, where they fused into a single population, resuspending old admixture variation. Each population contributed a different set of ancient alleles from which a new adaptive radiation assembled in record time, involving additional fusion-fission cycles. We argue that repeated fusion-fission cycles in the history of a lineage make adaptive radiation fast and predictable.
Community-wide genome sequencing reveals 30 years of Darwin’s finch evolution
Authors: Enbody Erik D. , Sendell-Price Ashley T. , Sprehn C. Grace , Rubin Carl-Johan , Visscher Peter M. , Grant B. Rosemary , Grant Peter R. , Andersson Leif
Published: September 2023

A fundamental goal in evolutionary biology is to understand the genetic architecture of adaptive traits. Using whole-genome data of 3955 of Darwin’s finches on the Galápagos Island of Daphne Major, we identified six loci of large effect that explain 45% of the variation in the highly heritable beak size of
Geospiza fortis,
a key ecological trait. The major locus is a supergene comprising four genes. Abrupt changes in allele frequencies at the loci accompanied a strong change in beak size caused by natural selection during a drought. A gradual change in
Geospiza scandens
occurred across 30 years as a result of introgressive hybridization with
G. fortis
. This study shows how a few loci with large effect on a fitness-related trait contribute to the genetic potential for rapid adaptive radiation.
Diverse functional polyethylenes by catalytic amination
Authors: Ciccia Nicodemo R. , Shi Jake X. , Pal Subhajit , Hua Mutian , Malollari Katerina G. , Lizandara-Pueyo Carlos , Risto Eugen , Ernst Martin , Helms Brett A. , Messersmith Phillip B. , Hartwig John F.
Published: September 2023

Functional polyethylenes possess valuable bulk and surface properties, but the limits of current synthetic methods narrow the range of accessible materials and prevent many envisioned applications. Instead, these materials are often used in composite films that are challenging to recycle. We report a Cu-catalyzed amination of polyethylenes to form mono- and bifunctional materials containing a series of polar groups and substituents. Designed catalysts with hydrophobic moieties enable the amination of linear and branched polyethylenes without chain scission or cross-linking, leading to polyethylenes with otherwise inaccessible combinations of functional groups and architectures. The resulting materials possess tunable bulk and surface properties, including toughness, adhesion to metal, paintability, and water solubility, which could unlock applications for functional polyethylenes and reduce the need for complex composites.
Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis
Authors: Wang Yijie , Li Qihao , Tao Bo , Angelini Marina , Ramadoss Sivakumar , Sun Baiming , Wang Ping , Krokhaleva Yuliya , Ma Feiyang , Gu Yiqian , Espinoza Alejandro , Yamauchi Ken , Pellegrini Matteo , Novitch Bennett , Olcese Riccardo , Qu Zhilin , Song Zhen , Deb Arjun
Published: September 2023

After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.
Valley-addressable monolayer lasing through spin-controlled Berry phase photonic cavities
Authors: Duan Xiaoyang , Wang Bo , Rong Kexiu , Liu Chieh-li , Gorovoy Vladi , Mukherjee Subhrajit , Kleiner Vladimir , Koren Elad , Hasman Erez
Published: September 2023

The spin-valley coupling between circularly polarized light and valley excitons in transition metal dichalcogenides provides the opportunity to generate and manipulate spin information by exploiting the valley degree of freedom. Here, we demonstrate a room-temperature valley-addressable tungsten disulfide monolayer laser in which the spin of lasing is controlled by the spin of pump without magnetic fields. This effect was achieved by integrating a tungsten disulfide monolayer into a photonic cavity that supports two orthogonal spin modes with high quality factors. The spin-pumped lasing effectively broke the population symmetry of valley excitons, resulting in highly coherent emission with valley-switchable radiation modes due to distinct laser thresholds. Our scheme provides a nanophotonic platform to develop versatile coherent spin-light sources operating at room temperature by actively manipulating spin-valley coupling in light-matter interactions.
Pandemics and their lessons
Foreign Bodies: Pandemics, Vaccines, and the Health of Nations
Simon Schama
Ecco, 2023. 480 pp.
Authors: Goldman Michael A.
Published: September 2023

Distrust and xenophobia have long been stumbling blocks during public health crises
In Science Journals
Authors: Hodges Kip , Osborne Ian S. , Neuhofer Daniela , Ash Caroline , Grocholski Brent , Yeston Jake S. , Foley John F. , Alderton Gemma , Lavine Marc S. , Simonti Corinne , Vignieri Sacha , Nusinovich Yevgeniya , Isles Hannah M.
Published: September 2023

Highlights from the
Science
family of journals
Feeling the heat
Authors: Kupferschmidt Kai
Published: September 2023

Researchers struggle to convey the complex impacts of climate warming on infectious disease
Deadly avian flu hits Galápagos
Authors: Stokstad Erik
Published: September 2023

Concerns rise for boobies, finches, and other endemic species
Impact of antibiotic pharmacokinetics in urine on recurrent bacteriuria following treatment of complicated urinary tract infections
Authors: Melnick David , Talley Angela K. , Gupta Vipul K. , Critchley Ian A. , Eckburg Paul B. , Hamed Kamal A. , Bhatt Nivedita , Moore Gary , Austin Daren , Rubino Christopher M. , Bhavnani Sujata M. , Ambrose Paul G.
Published: September 2023

The clinical relevance of bacteriuria following antibiotic treatment of complicated urinary tract infections in clinical trials remains controversial. We evaluated the impact of urine pharmacokinetics on the timing of recurrent bacteriuria in a recently completed trial that compared oral tebipenem pivoxil hydrobromide to intravenous ertapenem. The urinary clearance and urine dwell time of ertapenem were prolonged relative to tebipenem and were associated with a temporal difference in the repopulation of bladder urine with bacteria following treatment, potentially confounding the assessment of efficacy.
Centering relationships in the biology classroom
Authors: Siegesmund Amy
Published: September 2023

The landscape of higher education has changed significantly in recent years with a concomitant shift in the classroom. Science courses have historically been content-driven with the need to cover content driving curricular and pedagogical choices. However, educators are recognizing that the curricular approaches of years past no longer provide adequate support for students. A classroom that centers relationships—both among students as well as teachers and students—is one that is better positioned to foster a sense of belonging, science identity, and student success. Furthermore, an educator who builds a professional community and prioritizes self-care is the one who is better equipped to adapt to the ever-changing needs of students. Emphasizing the human component of education creates a classroom where students and teachers feel seen and valued and the educational experience is enriched for all.
The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication
Authors: Li Jie , Gui Qi , Liang Feng-Xia , Sall Joseph , Zhang Qingyue , Duan Yatong , Dhabaria Avantika , Askenazi Manor , Ueberheide Beatrix , Stapleford Kenneth A. , Pagano Michele
Published: September 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like other coronaviruses, replicates their genome in virus-induced cytosolic membrane-bound replication organelles (ROs). SARS-CoV-2 promotes the biogenesis of ROs by inducing the rearrangement of endoplasmic reticulum (ER) membranes. NSP3, NSP4, and NSP6 are transmembrane viral non-structural proteins (NSPs) and essential players in the formation of ROs. To understand how these three NSPs work synergistically with host-binding proteins, we performed affinity purifications followed by mass spectrometry analyses to study the host-viral protein-protein interactome of NSP3, NSP4, and NSP6 expressed individually and in combination. Through this analysis, we identified two host transmembrane proteins, REEP5 and TRAM1, as critical interacting partners of NSP3 that localize at the membrane of the RO. REEP5 interacts with TRAM1 endogenously and binds NSP3 during SARS-CoV-2 infection. REEP5 knockout reduces ER membrane rearrangements and inhibits SARS-CoV-2 replication. Collectively, our study shows that the host REEP5/TRAM1 complex binds NSP3, promoting RO biogenesis and viral replication.

IMPORTANCE

Generation of virus-host protein–protein interactions (PPIs) maps may provide clues to uncover SARS-CoV-2-hijacked cellular processes. However, these PPIs maps were created by expressing each viral protein singularly, which does not reflect the life situation in which certain viral proteins synergistically interact with host proteins. Our results reveal the host-viral protein-protein interactome of SARS-CoV-2 NSP3, NSP4, and NSP6 expressed individually or in combination. Furthermore, REEP5/TRAM1 complex interacts with NSP3 at ROs and promotes viral replication. The significance of our research is identifying virus-host interactions that may be targeted for therapeutic intervention.
Division of labor within psyllids: metagenomics reveals an ancient dual endosymbiosis with metabolic complementarity in the genus
Cacopsylla
Authors: Dittmer Jessica , Corretto Erika , Štarhová Serbina Liliya , Michalik Anna , Nováková Eva , Schuler Hannes
Published: September 2023

Hemipteran insects are well-known for their ancient associations with beneficial bacterial endosymbionts, particularly nutritional symbionts that provide the host with essential nutrients such as amino acids or vitamins lacking in the host’s diet. Therefore, these primary endosymbionts enable the exploitation of nutrient-poor food sources such as plant sap or vertebrate blood. In turn, the strictly host-associated lifestyle strongly impacts the genome evolution of the endosymbionts, resulting in small and degraded genomes. Over time, even the essential nutritional functions can be compromised, leading to the complementation or replacement of an ancient endosymbiont by another, more functionally versatile bacterium. Herein, we provide evidence for a dual primary endosymbiosis in several psyllid species. Using metagenome sequencing, we produced the complete genome sequences of both the primary endosymbiont “
Candidatus
Carsonella ruddii” and an as yet uncharacterized Enterobacteriaceae bacterium from four species of the genus
Cacopsylla
. The latter represents a new psyllid-associated endosymbiont clade for which we propose the name “
Candidatus
Psyllophila symbiotica.” Fluorescent
in situ
hybridization confirmed the co-localization of both endosymbionts in the bacteriome. The metabolic repertoire of
Psyllophila
is highly conserved across host species and complements the tryptophan biosynthesis pathway that is incomplete in the co-occurring
Carsonella
. Unlike co-primary endosymbionts in other insects, the genome of
Psyllophila
is almost as small as the one of
Carsonella
, indicating an ancient co-obligate endosymbiosis rather than a recent association to rescue a degrading primary endosymbiont.

IMPORTANCE

Heritable beneficial bacterial endosymbionts have been crucial for the evolutionary success of numerous insects by enabling the exploitation of nutritionally limited food sources. Herein, we describe a previously unknown dual endosymbiosis in the psyllid genus
Cacopsylla
, consisting of the primary endosymbiont “
Candidatus
Carsonella ruddii” and a co-occurring Enterobacteriaceae bacterium for which we propose the name “
Candidatus
Psyllophila symbiotica.” Its localization within the bacteriome and its small genome size confirm that
Psyllophila
is a co-primary endosymbiont widespread within the genus
Cacopsylla
. Despite its highly eroded genome,
Psyllophila
perfectly complements the tryptophan biosynthesis pathway that is incomplete in the co-occurring
Carsonella
. Moreover, the genome of
Psyllophila
is almost as small as
Carsonella
’s, suggesting an ancient dual endosymbiosis that has now reached a precarious stage where any additional gene loss would make the system collapse. Hence, our results shed light on the dynamic interactions of psyllids and their endosymbionts over evolutionary time.
The MprF homolog LysX synthesizes lysyl-diacylglycerol contributing to antibiotic resistance and virulence
Authors: Gill Cameron P. , Phan Christopher , Platt Vivien , Worrell Danielle , Andl Thomas , Roy Hervé
Published: September 2023

Lysyl-diacylglycerol (Lys-DAG) was identified three decades ago in
Mycobacterium phlei
, but the biosynthetic pathway and function of this aminoacylated lipid have since remained uncharacterized. Combining genetic methods, mass spectrometry, and biochemical approaches, we show that the multiple peptide resistance factor (MprF) homolog LysX from
Corynebacterium pseudotuberculosis
and two mycobacterial species is responsible for Lys-DAG synthesis. LysX is conserved in most Actinobacteria and was previously implicated in the synthesis of another modified lipid, lysyl-phosphatidylglycerol (Lys-PG), in
Mycobacterium tuberculosis
. Although we detected low levels of Lys-PG in the membrane of
C. pseudotuberculosis
, our data suggest that Lys-PG is not directly synthesized by LysX and may require an additional downstream pathway, which is as yet undefined. Our results show that LysX in
C. pseudotuberculosis
is a major factor of resistance against a variety of positively charged antibacterial agents, including cationic antimicrobial peptides (e.g., human peptide LL-37 and polymyxin B) and aminoglycosides (e.g., gentamycin and apramycin). Deletion of
lysX
caused an increase in cellular membrane permeability without dissipation of the membrane potential, suggesting that loss of the protein does not result in mechanical damage to the cell membrane. Furthermore,
lysX
-deficient cells exhibited an attenuated virulence phenotype in a
Galleria mellonella
infection model, supporting a role for LysX during infection. Altogether, Lys-DAG represents a novel molecular determinant for antimicrobial resistance and virulence that may be widespread in Actinobacteria and points to a richer landscape than previously realized of lipid components contributing to overall membrane physiology in this important bacterial phylum.

IMPORTANCE

In the past two decades, tRNA-dependent modification of membrane phosphatidylglycerol has been implicated in altering the biochemical properties of the cell surface, thereby enhancing the antimicrobial resistance and virulence of various bacterial pathogens. Here, we show that in several Actinobacteria, the multifunctional protein LysX attaches lysine to diacylglycerol instead of phosphatidylglycerol. We found that lysyl-diacylglycerol (Lys-DAG) confers high levels of resistance against various cationic antimicrobial peptides and aminoglycosides and also enhances virulence. Our data show that Lys-DAG is a lipid commonly found in important actinobacterial pathogens, including
Mycobacterium
and
Corynebacterium
species.
Hospitalisations related to nervous-system diseases in Australia, 1998–2019: a secular trend analysis
Authors: Abuhamdah Sawsan MA , Naser Abdallah Y
Published: September 2023

Objective

The burden of neurological disease-related disabilities and deaths is one of the most serious issues globally. We aimed to examine the hospitalisation profile related to nervous system diseases in Australia for the duration between 1998 and 2019.

Design

A secular trend analysis using a population-based dataset.

Setting

This analysis used a population-based study of hospitalised patients in Australia. Hospitalisation data were extracted from the National Hospital Morbidity Database, which collects sets of episode-level information for Australian patients admitted to all private and public hospitals.

Participants

All patients who were hospitalised in all private and public hospitalisations.

Primary outcome measure

Hospitalisation rates related to nervous system diseases.

Results

Hospitalisation rates increased by 1.04 times (from 650.36 (95% CI 646.73 to 654.00) in 1998 to 1328.90 (95% CI 1324.44 to 1333.35) in 2019 per 100 000 persons, p<0.01). Overnight-stay episodes accounted for 57.0% of the total number of hospitalisations. Rates of the same-day hospitalisation for diseases of the nervous system increased by 2.10-fold (from 219.74 (95% CI 217.63 to 221.86) in 1998 to 680.23 (95% CI 677.03 to 683.43) in 2019 per 100 000 persons). Rates of overnight-stay hospital admission increased by 42.7% (from 430.62 (95% CI 427.66 to 433.58) in 1998 to 614.70 (95% CI 611.66 to 617.75) in 2019 per 100 000 persons). ‘Episodic and paroxysmal disorders’ were the most prevalent reason for hospitalisation, which accounted for 49.0% of the total number of episodes. Female hospitalisation rates increased by 1.13-fold (from 618.23 (95% CI 613.24 to 623.22) in 1998 to 1316.33 (95% CI 1310.07 to 1322.58) in 2019 per 100 000 persons). Male hospitalisation rates increased by 86.4% (from 682.95 (95% CI 677.67 to 688.23) in 1998 to 1273.18 (95% CI 1266.98 to 1279.37) in 2019 per 100 000 persons).

Conclusion

Hospitalisation rates for neurological disorders in Australia are high, potentially owing to the ageing of the population. Males had greater rates of hospitalisation than females.
Quality improvement interventions to prevent the use of hospital services among nursing home residents: protocol for a systematic review and meta-analysis
Authors: Basso Ines , Gonella Silvia , Bassi Erika , Caristia Silvia , Campagna Sara , Dal Molin Alberto
Published: September 2023

Introduction

Quality improvement interventions are a promising strategy for reducing hospital services use among nursing home residents. However, evidence for their effectiveness is limited. It is unclear which characteristics of the quality improvement intervention and activities planned to facilitate implementation may promote fidelity to organisational and system changes. This systematic review and meta-analysis will assess the effectiveness of quality improvement interventions and implementation strategies aimed at reducing hospital services use among nursing home residents.

Methods and analysis

The MEDLINE, CINAHL, Cochrane Library, Embase and Web of Science databases will be comprehensively searched in September 2023. The eligible studies should focus on the implementation of a quality improvement intervention defined as the systematic, continuous approach that designs, tests and implements changes using real-time measurement to reduce hospitalisations or emergency department visits among long-stay nursing home residents. Quality improvement details and implementation strategies will be deductively categorised into effective practice and organisation of care taxonomy domains for delivery arrangements and implementation strategies. Quality and bias assessments will be completed using the Quality Improvement Minimum Quality Criteria Set and the Joanna Briggs Institute Critical Appraisal Tools.

The results will be pooled in a meta-analysis, by combining the natural logarithms of the rate ratios across the studies or by calculating the rate ratio using the generic inverse-variance method. Heterogeneity will be assessed using the I2or H2statistics if the number of included studies will be less than 10. Raw data will be requested from the authors, as required.

Ethics and dissemination

Ethical approval is not required. The results will be published in a peer-review journal and presented at (inter)national conferences.

PROSPERO registration number

CRD42022364195.
Statins exposure and acute pancreatitis: a retrospective cohort study using a large national insurance database
Authors: Ba Djibril M , Zhang Yue , Chinchilli Vernon M , Maranki Jennifer
Published: September 2023

Objectives

The association between the use of statins and the incidence of acute pancreatitis (AP) has yielded inconsistent findings. While statins have been implicated as an aetiology for drug-induced pancreatitis, more recent studies have found statin use is associated with a reduced risk of pancreatitis. We sought to examine the association between the use of any statin medications and the risk of AP using large real-world data.

Design

All data were collected retrospectively, but individuals were prospectively followed forward in time to determine the outcome of interest using International Classification of Diseases, 10th Revision, Clinical Modification codes indicating a diagnosis of AP. A stratified Cox proportional hazards regression model was conducted to examine the association of statins use with AP.

Settings

Merative MarketScan claims database 2017–2020.

Participants

Individuals who filled any statin prescriptions with at least 80% proportion of days covered between 1 January 2017 and 31 December 2017 and were continuously enrolled in the database from 2016 to 2020. We also identified non-users of statins and constructed multiple strata of individuals based on the 14 confounders of interest.

Results

Among 1 695 914 individuals, 226 314 had filled their statins prescription during the study period. Unadjusted incidence rates of AP generally showed higher rates among statins users. The unadjusted incidence rate and 95% CI per 1000 person-years of follow-up was 0.63 (95% CI: 0.61 to 0.66) for non-statin users, versus 0.92 (95% CI: 0.86 to 0.98) for statins users. However, a stratified Cox proportional hazards regression analysis yielded a HR of 0.92 (95% CI: 0.84 to 1.01) for statins users, indicating no difference between the two groups.

Conclusions

In this large real-world analysis, use of statins was not associated with a higher risk of AP in this US healthcare setting.
Specific versus general exercise programme in adults with subacromial impingement syndrome: a randomised controlled trial
Authors: Gutiérrez Espinoza Héctor , Araya-Quintanilla Felipe , Pinto-Concha Sebastian , Valenzuela-Fuenzalida Juan , López-Gil José Francisco , Ramírez-Velez Robinson
Published: September 2023

Objectives

Current evidence on the clinical effectiveness about the different types of exercises in the subacromial impingement syndrome (SIS) remains controversial. This study aims to compare the short-term (at 5 weeks) effects of a specific exercise programme with a general exercise programme on shoulder function in adults with SIS.

Methods

In total, 52 adults with SIS were randomly allocated to 5 weeks to perform specific exercises (experimental group, n=26) or general exercises (control group, n=26). The primary outcome was change in shoulder function, it was assessed using the Shoulder Pain and Disability Index (SPADI) from baseline to 5 weeks. Secondary end points included changes in upper limb function (Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire), pain intensity (Visual Analog Scale (VAS)) and kinesiophobia (Tampa Scale of Kinesiophobia (TSK)).

Results

All participants completed the trial. The between-group differences at 5 weeks were: SPADI, 13.5 points (95% CI: 4.3 to 15.6; ƞ2=0.22; p=0.001); DASH, 10.1 points (95% CI: 5.6 to 15.2; ƞ2=0.27; p<0.001); VAS at rest, 0.2 cm (95% CI: 0.1 to 0.3; ƞ2=0.07; p=0.553); VAS on movement, 1.7 cm (95% CI: 0.9 to 2.2; ƞ2=0.24; p<0.001); and TSK, 16.3 points (95% CI: 13.2 to 15.3; ƞ2=0.33; p<0.001). All differences favoured the experimental group and effect sizes were medium to large for most outcomes. Mediation analyses showed that the effect of the specific exercises on shoulder function was mediated by kinesiophobia (β=2.800; 95% CI: 1.063 to 4.907) and pain on movement (β= −0.690; 95% CI: −1.176 to −0.271).

Conclusion

In adults with SIS, specific exercises may have a larger effect than general exercises. However, most differences did not reach the minimum threshold to be considered clinically important and the evidence to support exercise as standard treatment warrant further study.

Trial registration number

Brazilian Registry of Clinical Trials UTN number U111-1245-7878. Registered on 17 January 2020 (https://ensaiosclinicos.gov.br/rg/RBR-4d5zcg).
Anti-slip regulation method for electric vehicles with four in-wheel motors based on the identification of slip ratio
Authors: Chen Qiping , Xu Wuhao , Lv Zongyu , Zeng Dequan , Zhong Chengping , Zeng Xiaochun
Published: September 2023

To improve the stability and acceleration of electric vehicles with four in-wheel motors under various road conditions, an anti-slip regulation method considering the identification of slip ratios is proposed. In this paper, the model of the whole vehicle is built, and the road identifier based on the tire model established by Burckhardt is designed. Then, an anti-slip controller that utilizes the variable universe fuzzy proportional integral derivative (PID) algorithm is established to adjust the driving torques of the four in-wheel motors according to the road conditions. The simulation results show that the designed control strategy can quickly and accurately identify the optimal slip ratio under each typical road condition and make the tire slip ratio approach the optimal slip ratio in a short time, so as to effectively improve the driving stability and dynamic performance of the vehicle.
SAPERO: a new tool for safety analyses in advanced radiotherapy
Authors: Giardina Mariarosa , Tomarchio Elio , Buffa Pietro , Ferrera Giuseppe , Abbate Boris Federico , Iacoviello Giuseppina , Marsala Laura , Carruba Giuseppe , Galeazzo Fabiola , Alfano Giuseppina Pia
Published: September 2023

Improving safety standards in advanced radiotherapy technologies, where historical experience is not sufficient due to innovation aspects, raises the need to perform studies using new tools that follow a holistic view of the process chain. Such studies are useful to identify additional critical elements compared to safety analyses carried out by classic tools. In this field, SAPERO (La SicurezzA del PazientE: tecniche avanzate ed innovative per la valutazione del rischio di eventi indesiderati all'interno del percorso assistenziale nel settore RadioterapicO) is a new assessment tool that allows to use integrated of Hierarchical Task Analysis (HTA); Failure Mode Effects and Criticality Analysis (FMECA); Cognitive Task Analysis (CTA); Human Error Assessment Reduction Technique (HEART). The methodological approaches have been suitably modified to address their operating in the medical sector under study. Some improvements have concerned the application of the fuzzy theory in FMECA and the use of a linguistic approach in HEART. In this paper, SAPERO application on a case study related to treatment procedures in helical tomotherapy performed at the radiotherapy department of ARNAS Civico hospital, Italy, is described. The results have allowed to provide suggestions aimed to improve the examined process.
LEAF: Navigating Concept Drift in Cellular Networks
Authors: Liu Shinan , Bronzino Francesco , Schmitt Paul , Bhagoji Arjun Nitin , Feamster Nick , Crespo Hector Garcia , Coyle Timothy , Ward Brian
Published: September 2023

Operational networks commonly rely on machine learning models for many tasks, including detecting anomalies, inferring application performance, and forecasting demand. Yet, model accuracy can degrade due to concept drift, whereby the relationship between the features and the target to be predicted changes. Mitigating concept drift is an essential part of operationalizing machine learning models in general, but is of particular importance in networking's highly dynamic deployment environments. In this paper, we first characterize concept drift in a large cellular network for a major metropolitan area in the United States. We find that concept drift occurs across many important key performance indicators (KPIs), independently of the model, training set size, and time interval---thus necessitating practical approaches to detect, explain, and mitigate it. We then show that frequent model retraining with newly available data is not sufficient to mitigate concept drift, and can even degrade model accuracy further. Finally, we develop a new methodology for concept drift mitigation, Local Error Approximation of Features (LEAF). LEAF works by detecting drift; explaining the features and time intervals that contribute the most to drift; and mitigates it using forgetting and over-sampling. We evaluate LEAF against industry-standard mitigation approaches (notably, periodic retraining) with more than four years of cellular KPI data. Our initial tests with a major cellular provider in the US show that LEAF consistently outperforms periodic and triggered retraining on complex, real-world data while reducing costly retraining operations.
Securing Name Resolution in the IoT: DNS over CoAP
Authors: Lenders Martine S. , Amsüss Christian , Gündogan Cenk , Nawrocki Marcin , Schmidt Thomas C. , Wählisch Matthias
Published: September 2023

In this paper, we present the design, implementation, and analysis of DNS over CoAP~(DoC), a new proposal for secure and privacy-friendly name resolution of constrained IoT devices. We implement different design choices of DoC in RIOT, an open-source operating system for the IoT, evaluate performance measures in a testbed, compare with DNS over UDP and DNS over DTLS, and validate our protocol design based on empirical DNS IoT data. Our findings indicate that plain DoC is on par with common DNS solutions for the constrained IoT but significantly outperforms when additional standard features of CoAP are used such as caching. With OSCORE, we can save more than 10 kBytes of code memory compared to DTLS, when a CoAP application is already present, and retain the end-to-end trust chain with intermediate proxies, while leveraging features such as group communication or encrypted en-route caching. We also discuss a compression scheme for very restricted links that reduces data by up to 70%.
Design, Synthesis, and Biological Activity Evaluation of Novel AZT and Adenosine-Derived 1,2,3-Triazoles
Authors: Le Duc Anh , Truong Ngoc Hung , Vu Van Dung , Doan Thanh Huyen , Le Minh Tri , Nguyen Thi Huong , Nguyen Manh Cuong , Do Huu Nghi , Ninh Duc Bao , Le Phong , Nguyen Thi Phuong Thao , Tran Khac Vu , Luu Van Chinh
Published: September 2023

CuSO4/hydrazine hydrate was used as a catalyst system for copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) of AZT and 5′-azido adenosine with terminal alkynes to give 30 novel 1,2,3-triazole derivatives. Screening for their anticancer, anti-inflammatory, angiotensin-converting enzyme 2 (ACE2), and 3C-like protease (3CLpro) inhibitory activities showed that several triazoles of AZT containing murayafoline A and indirubin-3′-oxime inhibited the growth of HepG2 and LU-1 with the IC50 values ranging from 11.01 to 19.87 μg/mL. Besides that, some triazole derivatives of adenosine exhibited anti-inflammatory activity against RAW264.7 cells with the IC50 values within an interval of 12.00–59.48.00 μg/mL. Especially, two triazoles of adenosine with indirubin-3′-oxime at O- and N1 positions expressed the ACE2 and 3CLpro inhibitory activities in which the triazole of adenosine with indirubin-3′-oxime at N1 inhibited both ACE2 and 3CLpro inhibitory activities with IC50 values of 135.62 and 142.95 μg/mL, respectively.
Striatal Lacunar Infarction in a Late Preterm Infant Born to a Mother with Active Peripartum SARS-CoV-2 Infection
Authors: Hochmayr Christoph , Hammerl Marlene , Winkler Ira , Schweigmann Gisela , Kiechl-Kohlendorfer Ursula , Griesmaier Elke , Posod Anna
Published: September 2023

Background. The current literature suggests that neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections generally have a mild course. Data on how in utero exposure to maternal infection affects neonatal health outcomes are limited, but there is evidence that neurological damage to the fetus and thromboembolic events may occur. Case Presentation. We describe the case of a late preterm infant, who presented with striatal lacunar infarction in the neonatal period, born to a mother with active peripartum SARS-CoV-2 infection. Diagnostic workup did not identify risk factors apart from the maternal SARS-CoV-2 infection. Repeated reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 using oropharyngeal swab specimens of the patient were negative. IgG, but not IgM antibodies against spike protein S1 receptor-binding domain (S1RBD) epitope were detectable in umbilical cord blood and neonatal serum collected at 48 hours of life. Anti-SARS-CoV-2 total antibody titers against nucleocapsid protein in umbilical cord blood were negative. Conclusions. Bearing in mind a possible association of in utero exposure to SARS-CoV-2 and neonatal thromboembolic events, neonatologists should be aware of these complications even in well-appearing preterm infants.
LE‐YOLOv5: A Lightweight and Efficient Road Damage Detection Algorithm Based on Improved YOLOv5
Authors: Diao Zhuo , Huang Xianfu , Liu Han , Liu Zhanwei
Published: September 2023

Road damage detection is very important for road safety and timely repair. The previous detection methods mainly rely on humans or large machines, which are costly and inefficient. Existing algorithms are computationally expensive and difficult to arrange in edge detection devices. To solve this problem, we propose a lightweight and efficient road damage detection algorithm LE‐YOLOv5 based on YOLOv5. We propose a global shuffle attention module to improve the shortcomings of the SE attention module in MobileNetV3, which in turn builds a better backbone feature extraction network. It greatly reduces the parameters and GFLOPS of the model while increasing the computational speed. To construct a simple and efficient neck network, a lightweight hybrid convolution is introduced into the neck network to replace the standard convolution. Meanwhile, we introduce the lightweight coordinate attention module into the cross‐stage partial network module that was designed using the one‐time aggregation method. Specifically, we propose a parameter‐free attentional feature fusion (PAFF) module, which significantly enhances the model’s ability to capture contextual information at a long distance by guiding and enhancing correlation learning between the channel direction and spatial direction without introducing additional parameters. The K‐means clustering algorithm is used to make the anchor boxes more suitable for the dataset. Finally, we use a label smoothing algorithm to improve the generalization ability of the model. The experimental results show that the LE‐YOLOv5 proposed in this document can stably and effectively detect road damage. Compared to YOLOv5s, LE‐YOLOv5 reduces the parameters by 52.6% and reduces the GFLOPS by 57.0%. However, notably, the mean average precision (mAP) of our model improves by 5.3%. This means that LE‐YOLOv5 is much more lightweight while still providing excellent performance. We set up visualization experiments for multialgorithm comparative detection in a variety of complex road environments. The experimental results show that LE‐YOLOv5 exhibits excellent robustness and reliability in complex road environments.
Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma
Authors: Welsh Seth J. , Barwick Benjamin G. , Meermeier Erin W. , Riggs Daniel L. , Shi Chang-Xin , Zhu Yuan Xiao , Sharik Meaghen E. , Du Megan T. , Abrego Rocha Leslie D. , Garbitt Victoria M. , Stein Caleb K. , Petit Joachim L. , Meurice Nathalie , Tafoya Alvarado Yuliza , Fonseca Rodrigo , Todd Kennedi T. , Brown Sochilt , Hammond Zachery J. , Cuc Nicklus H. , Wittenberg Courtney , Herzog Camille , Roschke Anna V. , Demchenko Yulia N. , Chen Wei-dong D. , Li Peng , Liao Wei , Leonard Warren J. , Lonial Sagar , Bahlis Nizar J. , Neri Paola , Boise Lawrence H. , Chesi Marta , Bergsagel P. Leif
Published: September 2023

Multiple myeloma (MM) is a malignancy that is often driven by MYC and that is sustained by IRF4, which are upregulated by super-enhancers. IKZF1 and IKZF3 bind to super-enhancers and can be degraded using immunomodulatory imide drugs (IMiD). Successful IMiD responses downregulate MYC and IRF4; however, this fails in IMiD-resistant cells. MYC and IRF4 downregulation can also be achieved in IMiD-resistant tumors using inhibitors of BET and EP300 transcriptional coactivator proteins; however, in vivo these drugs have a narrow therapeutic window. By combining IMiDs with EP300 inhibition, we demonstrate greater downregulation of MYC and IRF4, synergistic killing of myeloma in vitro and in vivo, and an increased therapeutic window. Interestingly, this potent combination failed where MYC and IRF4 expression was maintained by high levels of the AP-1 factor BATF. Our results identify an effective drug combination and a previously unrecognized mechanism of IMiD resistance.

Significance:

These results highlight the dependence of MM on IKZF1-bound super-enhancers, which can be effectively targeted by a potent therapeutic combination pairing IMiD-mediated degradation of IKZF1 and IKZF3 with EP300 inhibition. They also identify AP-1 factors as an unrecognized mechanism of IMiD resistance in MM.

See related article by Neri, Barwick, et al., p. 56.

See related commentary by Yun and Cleveland, p. 5.

This article is featured in Selected Articles from This Issue, p. 4