bluuebunny/crossref_metadata_2025 huggingface dataset:
Shale Oil Shut-In and Flowback Mechanism and Optimization Strategy
Authors: Lu Zhiwei , Li Xiang , Che Mingguang , Li Xizhe
Published: June 2024

Shut-in and flowback are critical stages following hydraulic fracturing in shale oil wells. Researching the distribution of reservoir pressure and fluid flow mechanism during shut-in and flowback is important for optimizing these procedures, thereby enhancing well productivity. Therefore, based on the flow mechanism of shale oil, this article establishes a flow equation considering imbibition and seepage, using linear source superposition equivalent to the pressure distribution generated by hydraulic fracturing as the initial condition. The PEBI (Perpendicular BIsection) grid is used to divide the grid for multistage fractured horizontal wells. The simulation results reveal that large-volume fracturing leads to the formation of a high-pressure zone around the wellbore, significantly surpassing the original reservoir pressure, termed as the high-energy band. This high-energy band is demarcated from the original reservoir pressure by the pressure boundary line (PBL). During production, a double-pressure funnel (DPF) manifests within the reservoir, generating a region with the utmost pressure at a specific position within the high-energy band, known as the pressure peak line. Oil located beyond the pressure peak line is unable to flow toward the wellbore. According to the DPF theory of shale oil, fracturing technology should be adopted to form long straight fractures as far as possible whenever feasible to cross the high-energy band. The shale oil optimal duration for shut-in is contingent upon the movement rate of the pressure boundary and the shale imbibition curve.
Lithium-Ion Battery Health State Estimation Based on Feature Reconstruction and Optimized Least Squares Support Vector Machine
Authors: Wu Tiezhou , Kang Jian , Zhu Junchao , Tu Te
Published: June 2024

The state of health (SOH) of a battery is the main indicator of battery life. In order to improve the SOH estimation accuracy, a model framework for lithium-ion battery health state estimation with feature reconstruction and improved least squares support vector machine is proposed. First, the indirect health features (HF) are obtained by processing multiple health features extracted from the charging and discharging phases through principal component analysis to remove the information redundancy among multiple features. Subsequently, multiple smooth component subsequences of different frequencies are obtained by using variational modal decomposition to efficiently capture the overall downtrend and regeneration fluctuations of the data. Then, use the sparrow search algorithm to optimize the least squares support vector machine to build an estimation model, predict and superimpose the reconstructed fusion features of multiple feature subsequences. Finally, use the mapping relationship between the reconstructed HF and the SOH for the estimation. The NASA battery dataset and the University of Maryland battery dataset (CACLE) are used to perform validation tests on multiple batteries with different cycle intervals. The results show that the mean absolute error and root mean square error are less than 1% and the method has high-estimation accuracy and robustness.
A Moving Horizon Estimation for a Class of Soft Continuum Manipulators
Authors: Bastos Guaraci
Published: June 2024

This work proposes a formulation for the moving horizon estimation technique considering both states and parameters obtained simultaneously with reduced estimation issues. The parameters can be either constant or time-varying, while states are related to complex output trajectories related to underactuated systems. Particularly, the proposed formulation considers additional equality constraints as a counterpart of the dynamics tube-model predictive control. Thus, it becomes less dependent on probabilistic information, such as probability density function and covariance of the process noise. In addition, the calibration of the method parameters has less sensitivity and driven by the tube constraints. The proposed approach can be applied in different systems; however, here it is detailed for a class of soft continuum manipulators with fluidic actuation through a variable flowrate and demonstrated with numerical simulations in planar motion. Results indicate robustness of the algorithm estimation in a challenging scenario arising from underactuation as well as in the presence of uncertainty and external disturbance, while simultaneously states and a vector of structural parameters are coherently estimated.
Infrared Emission for Heat Radiation From Micro-Cone Textured Metallic Sheet Device With Semi-Regular Alignment
Authors: Aizawa Tatsuhiko , Nakata Hiroki , Nasu Takeshi
Published: June 2024

A micro-cone textured copper sheet was fabricated as an emitter of electromagnetic waves in the near-infrared (IR) to the far-IR wavelengths. The micro-cone texture was aligned in semiregular by varying the micro-cone size parameters. The micro-cone height (H) was varied from 0.5 μm to 4 μm in average. Scanning electron microscopy (SEM) analysis was utilized to characterize the microstructure of micro-cone textures and to measure the population of micro-cone height (H), its root diameter (B), and pitch (D) with aid of the image processing and computational geometry. This emittance was measured by Fourier transformation-infrared (FT-IR) to investigate the micro-cone size effect on the resonant wavelengths for IR-emission. This height population P(H) was compared to the IR emission spectrum, which was measured by the FT-IR. Even varying the average height of micro-cone textures, the IR-emission wavelength (λ) abided by the resonance condition by λ ∼ 2 × H within the standard deviation of heights and wavelengths. The radiation heat flux from this emitter to objective body in vacuum was experimentally estimated to describe the heat transportation from this microtextured emitter. Through the heat radiation experiment in vacuum, the emitted heat flux was estimated to be 58 W/m2 by the one-dimensional heat balance between the heating rate of objective body and the radiated heat flux.
Random forest machine-learning algorithm classifies white- and brown-rot fungi according to the number of the genes encoding Carbohydrate-Active enZyme families
Authors: Hasegawa Natsuki , Sugiyama Masashi , Igarashi Kiyohiko
Published: June 2024

Wood-rotting fungi play an important role in the global carbon cycle because they are the only known organisms that digest wood, the largest carbon stock in nature. In the present study, we used linear discriminant analysis and random forest (RF) machine learning algorithms to predict white- or brown-rot decay modes from the numbers of genes encoding Carbohydrate-Active enZymes with over 98% accuracy. Unlike other algorithms, RF identified specific genes involved in cellulose and lignin degradation, including auxiliary activities (AAs) family 9 lytic polysaccharide monooxygenases, glycoside hydrolase family 7 cellobiohydrolases, and AA family 2 peroxidases, as critical factors. This study sheds light on the complex interplay between genetic information and decay modes and underscores the potential of RF for comparative genomics studies of wood-rotting fungi.

IMPORTANCE

Wood-rotting fungi are categorized as either white- or brown-rot modes based on the coloration of decomposed wood. The process of classification can be influenced by human biases. The random forest machine learning algorithm effectively distinguishes between white- and brown-rot fungi based on the presence of Carbohydrate-Active enZyme genes. These findings not only aid in the classification of wood-rotting fungi but also facilitate the identification of the enzymes responsible for degrading woody biomass.
DarA—the central processing unit for the integration of osmotic with potassium and amino acid homeostasis in
Bacillus subtilis
Authors: Warneke Robert , Herzberg Christina , Weiß Martin , Schramm Thorben , Hertel Dietrich , Link Hannes , Stülke Jörg
Published: June 2024

Cyclic di-adenosine monophosphate (c-di-AMP) is a second messenger involved in diverse metabolic processes including osmolyte uptake, cell wall homeostasis, as well as antibiotic and heat resistance. This study investigates the role of the c-di-AMP receptor protein DarA in the osmotic stress response in
Bacillus subtilis
. Through a series of experiments, we demonstrate that DarA plays a central role in the cellular response to osmotic fluctuations. Our findings show that DarA becomes essential under extreme potassium limitation as well as upon salt stress, highlighting its significance in mediating osmotic stress adaptation. Suppressor screens with
darA
mutants reveal compensatory mechanisms involving the accumulation of osmoprotectants, particularly potassium and citrulline. Mutations affecting various metabolic pathways, including the citric acid cycle as well as glutamate and arginine biosynthesis, indicate a complex interplay between the osmotic stress response and metabolic regulation. In addition, the growth defects of the
darA
mutant during potassium starvation and salt stress in a strain lacking the high-affinity potassium uptake systems KimA and KtrAB can be rescued by increased affinity of the remaining potassium channel KtrCD or by increased expression of
ktrD,
thus resulting in increased potassium uptake. Finally, the
darA
mutant can respond to salt stress by the increased expression of MleN , which can export sodium ions.

IMPORTANCE

Environmental bacteria are exposed to rapidly changing osmotic conditions making an effective adaptation to these changes crucial for the survival of the cells. In Gram-positive bacteria, the second messenger cyclic di-AMP plays a key role in this adaptation by controlling (i) the influx of physiologically compatible organic osmolytes and (ii) the biosynthesis of such osmolytes. In several bacteria, cyclic di-adenosine monophosphate (c-di-AMP) can bind to a signal transduction protein, called DarA, in
Bacillus subtilis
. So far, no function for DarA has been discovered in any organism. We have identified osmotically challenging conditions that make DarA essential and have identified suppressor mutations that help the bacteria to adapt to those conditions. Our results indicate that DarA is a central component in the integration of osmotic stress with the synthesis of compatible amino acid osmolytes and with the homeostasis of potassium, the first response to osmotic stress.
A broadly neutralizing human monoclonal antibody generated from transgenic mice immunized with HCMV particles limits virus infection and proliferation
Authors: Atanasoff Kristina E. , Parsons Andrea J. , Ophir Sabrina I. , Lurain Nell , Kraus Thomas , Moran Thomas , Duty J. Andrew , Tortorella Domenico
Published: June 2024

Human cytomegalovirus (HCMV) is a β-herpesvirus that poses severe disease risk for immunocompromised patients who experience primary infection or reactivation. Development and optimization of safe and effective anti-HCMV therapeutics is of urgent necessity for the prevention and treatment of HCMV-associated diseases in diverse populations. The use of neutralizing monoclonal antibodies (mAbs) to limit HCMV infection poses a promising therapeutic strategy, as anti-HCMV mAbs largely inhibit infection by targeting virion glycoprotein complexes. In contrast, the small-molecule compounds currently approved for patients (e.g., ganciclovir, letermovir, and maribavir) target later stages of the HCMV life cycle. Here, we present a broadly neutralizing human mAb, designated 1C10, elicited from a VelocImmune mouse immunized with infectious HCMV particles. Clone 1C10 neutralizes infection after virion binding to cells by targeting gH/gL envelope complexes and potently reduces infection of diverse HCMV strains in fibroblast, trophoblast, and epithelial cells. Antibody competition assays found that 1C10 recognizes a region of gH associated with broad neutralization and binds to soluble pentamer in the low nanomolar range. Importantly, 1C10 treatment significantly reduced virus proliferation in both fibroblast and epithelial cells. Further, the combination treatment of mAb 1C10 with ganciclovir reduced HCMV infection and proliferation in a synergistic manner. This work characterizes a neutralizing human mAb for potential use as a HCMV treatment, as well as a possible therapeutic strategy utilizing combination-based treatments targeting disparate steps of the viral life cycle. Collectively, the findings support an antibody-based therapy to effectively treat patients at risk for HCMV-associated diseases.

IMPORTANCE

Human cytomegalovirus is a herpesvirus that infects a large proportion of the population and can cause significant disease in diverse patient populations whose immune systems are suppressed or compromised. The development and optimization of safe anti-HCMV therapeutics, especially those that have viral targets and inhibition mechanisms different from current HCMV treatments, are of urgent necessity to better public health. Human monoclonal antibodies (mAbs) that prevent HCMV entry of cells were identified by immunizing transgenic mice and screened for broad and effective neutralization capability. Here, we describe one such mAb, which was found to target gH/gL envelope complexes and effectively limit HCMV infection and dissemination. Further, administration of the antibody in combination with the antiviral drug ganciclovir inhibited HCMV in a synergistic manner, highlighting this approach and the use of anti-HCMV mAbs more broadly, as a potential therapeutic strategy for the treatment of diverse patient populations.
Genomic and epidemiological evidence for the emergence of a
L. infantum/L. donovani
hybrid with unusual epidemiology in northern Italy
Authors: Bruno F. , Castelli G. , Li B. , Reale S. , Carra E. , Vitale F. , Scibetta S. , Calzolari M. , Varani S. , Ortalli M. , Franceschini E. , Gennari W. , Rugna G. , Späth G. F.
Published: June 2024

Leishmania
(
L
.)
infantum
is one of the main causative agents of animal and human leishmaniasis across many endemic areas in South America, Europe, North Africa, and Asia. Despite its clinical significance, little is known about the genetic diversity of
L. infantum
circulating in a given endemic area. Here, we investigate this important open question by applying a comparative genomics approach to seven
L. infantum
isolates from different hosts and Italian regions, including the northern part of the country (Emilia-Romagna, RER), Sicily, and Sardinia, as an initial attempt to explore the breadth of parasite genetic heterogeneity in Italy. Additionally, microsatellite analysis was carried out to compare the isolates from RER with other 70
L
.
infantum
strains from the same region as well as 65 strains belonging to the
L. donovani
complex from other countries. We revealed important karyotypic instability and identified strain-specific changes in gene dosage, which affected important virulence factors such as amastins and surface antigen-like proteins. Single nucleotide polymorphism-based clustering analysis of these genomes together with over 80 publicly available
L. infantum
and
L. donovani
genomes placed the Italian isolates into three geographically distinct clusters within the Mediterranean basin and uncovered three isolates clustering with putative
L. infantum/L. donovani
hybrids isolated in Cyprus. As judged by microsatellite profiling, these hybrid isolates are representative of a sub-population of parasites circulating in northern Italy that preferentially infect humans but not dogs. Our results place Italy at the crossroads of
L. infantum
infection in the Mediterranean and call attention to the public health risk represented by the introduction of non-European
Leishmania
species.

IMPORTANCE

This study closes important knowledge gaps with respect to
Leishmania (L.) infantum
genetic heterogeneity in a given endemic country, as exemplified here for Italy, and reveals genetic hybridization as a main cause for re-emerging human leishmaniasis in northern Italy. The observed high diversity of
Leishmania
parasites on the Italian peninsula suggests different geographical origins, with genomic adaptation to various ecologies affecting both pathogenicity and transmission potential. This is documented by the discovery of a putative
L. infantum
/
L. donovani
hybrid strain, which has been shown to preferentially infect humans but not dogs. Our results provide important information to health authorities, which need to consider the public health risk represented by the introduction of new
Leishmania
species into EU countries due to population displacement or travel from countries where exotic/allochthonous parasite species are endemic.
Mriyaviruses: small relatives of giant viruses
Authors: Yutin Natalya , Mutz Pascal , Krupovic Mart , Koonin Eugene V.
Published: June 2024

The phylum
Nucleocytoviricota
consists of large and giant viruses that range in genome size from about 100 kilobases (kb) to more than 2.5 megabases. Here, using metagenome mining followed by extensive phylogenomic analysis and protein structure comparison, we delineate a distinct group of viruses with double-stranded (ds) DNA genomes in the range of 35–45 kb that appear to be related to the
Nucleocytoviricota
. In phylogenetic trees of the conserved double jelly-roll major capsid proteins (MCPs) and DNA packaging ATPases, these viruses do not show affinity to any particular branch of the
Nucleocytoviricota
and accordingly would comprise a class which we propose to name “
Mriyaviricetes
” (after Ukrainian “mriya,” dream). Structural comparison of the MCP suggests that, among the extant virus lineages, mriyaviruses are the closest one to the ancestor of the
Nucleocytoviricota
. In the phylogenetic trees, mriyaviruses split into two well-separated branches, the family
Yaraviridae
and proposed new family “
Gamadviridae.
” The previously characterized members of these families, yaravirus and
Pleurochrysis
sp. endemic viruses, infect amoeba and haptophytes, respectively. The genomes of the rest of the mriyaviruses were assembled from metagenomes from diverse environments, suggesting that mriyaviruses infect various unicellular eukaryotes. Mriyaviruses lack DNA polymerase, which is encoded by all other members of the
Nucleocytoviricota
, and RNA polymerase subunits encoded by all cytoplasmic viruses among the
Nucleocytoviricota
, suggesting that they replicate in the host cell nuclei. All mriyaviruses encode a HUH superfamily endonuclease that is likely to be essential for the initiation of virus DNA replication via the rolling circle mechanism.

IMPORTANCE

The origin of giant viruses of eukaryotes that belong to the phylum
Nucleocytoviricota
is not thoroughly understood and remains a matter of major interest and debate. Here, we combine metagenome database searches with extensive protein sequence and structure analysis to describe a distinct group of viruses with comparatively small genomes of 35–45 kilobases that appear to comprise a distinct class within the phylum
Nucleocytoviricota
that we provisionally named “
Mriyaviricetes
.” Mriyaviruses appear to be the closest identified relatives of the ancestors of the
Nucleocytoviricota
. Analysis of proteins encoded in mriyavirus genomes suggests that they replicate their genome via the rolling circle mechanism that is unusual among viruses with double-stranded DNA genomes and so far not described for members of
Nucleocytoviricota
.
Multicenter retrospective genomic characterization of carbapenemase-producing
Acinetobacter baumannii
isolates from Jiangxi patients 2021–2022: identification of a novel international clone, IC11
Authors: Xu An , Li Min , Hang Yaping , Zeng Lingbing , Zhang Xuefei , Hu Yiyi , Guo Qinglan , Wang Minggui
Published: June 2024

This study aimed to characterize carbapenem-resistant
Acinetobacter baumannii
(CRAB) isolates from Jiangxi patients using whole-genome sequencing (WGS). We subjected 100 clinical CRAB strains isolated from the three local largest teaching hospitals to WGS and antimicrobial susceptibility testing. Molecular epidemiology was investigated using multilocus sequence typing, core genome multilocus typing, core genome single-nucleotide polymorphism phylogeny, and pulsed-field gel electrophoresis. The most prevalent acquired carbapenemase was
bla
OXA-23
, predominant in all isolates (100%). Isolates belonging to the dominating international clone IC2 accounted for 92% of all isolates. International IC11 (ST164
Pas
/ST1418
Ox
) clone was found in an additional 8% (eight isolates), with seven isolates (87.5%) carrying an acquired additional
bla
NDM-1
carbapenemase. The
oxa23
-associated Tn
2009
, either alone or in a tandem repeat structure containing four copies of
bla
OXA-23
, was discovered in 62% (57 isolates) of IC2. The
oxa23
-associated Tn
2006
was identified in 38% (35 isolates) of IC2 and all IC11 isolates. A putative conjugative RP-T1 (formerly RepAci6) plasmid with
bla
OXA-23
in Tn
2006
within AbaR4, designated pSRM1.1, was found in IC2
A. baumannii
strain SRM1. The
bla
NDM-1
gene found in seven IC11 isolates was located on a novel Tn
6924
-like transposon, a first-time report in IC11. These findings underscore the significant importance of real-time surveillance to prevent the further spread of CRAB.

IMPORTANCE

Carbapenem-resistant
Acinetobacter baumannii
(CRAB) is notorious for causing difficult-to-treat infections. To elucidate the molecular and clinical epidemiology of CRAB in Jiangxi, clinical CRAB isolates were collected and underwent whole-genome sequencing and antibiotic susceptibility phenotyping. Key findings included the predominance of OXA-23-producing IC2
A. baumannii
, marked by the emergence of OXA-23 and NDM-1-producing IC11 strains.
A limited concentration range of diaphorin, a polyketide produced by a bacterial symbiont of the Asian citrus psyllid, promotes the
in vitro
gene expression with bacterial ribosomes
Authors: Takasu Rena , Izu Takashi , Nakabachi Atsushi
Published: June 2024

Diaphorin is a polyketide produced by “
Candidatus
Profftella armatura” (
Gammaproteobacteria: Burkholderiales
), an obligate symbiont of a devastating agricultural pest, the Asian citrus psyllid
Diaphorina citri
(Hemiptera: Psyllidae). Physiological concentrations of diaphorin, which
D. citri
contains at levels as high as 2–20 mM, are inhibitory to various eukaryotes and
Bacillus subtilis
(
Firmicutes: Bacilli
) but promote the growth and metabolic activity of
Escherichia coli
(
Gammaproteobacteria: Enterobacterales
). Our previous study demonstrated that 5-mM diaphorin, which exhibits significant inhibitory and promoting effects on cultured
B. subtilis
and
E. coli
, respectively, inhibits
in vitro
gene expression utilizing purified
B. subtilis
and
E. coli
ribosomes. This suggested that the adverse effects of diaphorin on
B. subtilis
are partly due to its influence on gene expression. However, the result appeared inconsistent with the positive impact on
E. coli
. Moreover, the diaphorin concentration in bacterial cells, where genes are expressed
in vivo
, may be lower than in culture media. Therefore, the present study analyzed the effects of 50 and 500 µM of diaphorin on bacterial gene expression using the same analytical method. The result revealed that this concentration range of diaphorin, in contrast to 5-mM diaphorin, promotes the
in vitro
translation with the
B. subtilis
and
E. coli
ribosomes, suggesting that the positive effects of diaphorin on
E. coli
are due to its direct effects on translation. This study demonstrated for the first time that a pederin-type compound promotes gene expression, establishing a basis for utilizing its potential in pest management and industrial applications.

IMPORTANCE

This study revealed that a limited concentration range of diaphorin, a secondary metabolite produced by a bacterial symbiont of an agricultural pest, promotes cell-free gene expression utilizing substrates and proteins purified from bacteria. The unique property of diaphorin, which is inhibitory to various eukaryotes and
Bacillus subtilis
but promotes the growth and metabolic activity of
Escherichia coli
, may affect the microbial flora of the pest insect, potentially influencing the transmission of devastating plant pathogens. Moreover, the activity may be exploited to improve the efficacy of industrial production by
E. coli,
which is often used to produce various important materials, including pharmaceuticals, enzymes, amino acids, and biofuels. This study elucidated a part of the mechanism by which the unique activity of diaphorin is expressed, constructing a foundation for applying the distinct property to pest management and industrial use.
Turbidity currents regulate the transport and settling of microplastics in a deep-sea submarine canyon
Authors: Zhang Xiaodong , Liu Zhifei , Li Daoji , Zhao Yulong , Zhang Yanwei
Published: June 2024

Microplastics are widely distributed in deep oceans, with some of the highest concentrations reported in submarine canyons, which are thought to be closely related to turbidity currents. However, the turbidity current role in microplastic transport and deposition is poorly understood. Here, we present temporal variation in microplastic abundance and settling flux from sediment trap observations on the levee of Gaoping Canyon, offshore Taiwan, where turbidity currents occur frequently. The results showed that relatively high microplastic abundance and flux were consistent with the increases of near-bottom suspended sediment concentration caused by turbidity currents. The microplastics, dominated by polypropylene (59%) and polyethylene (21%), were probably derived from Taiwan coastal resuspension and river input and then transported into the submarine canyon by typhoon- or earthquake-triggered turbidity currents. During the turbidity currents, the average microplastic abundance and flux was 4137 particles per kilogram and 40.11 particles per square meter per day, respectively, showing an increase of 49% and 270%, respectively, compared to non–turbidity current periods. The total microplastic flux during the turbidity currents accounted for ~76% of annual flux. Our study highlights turbidity currents to be the major hydrodynamic process in regulating microplastic transport and settling in a submarine canyon.
Microcornea, cerebellar hypoplasia and hyperlax joints—unusual combo in rare Ehlers-Danlos syndrome—musculocontractural type 1
Authors: Umapathy Navin , Thirugnana Sambanda Moorthy Balakrishnan , Azhagar Nambi Santhi Vaanmathi , Nair Lal D V
Published: June 2024

Ehlers-Danlos syndrome is a group of connective tissue disorders with 14 subtypes, involving joint hyperlaxity, tissue fragility, hypertensive skin and other systemic organs with an incidence of 1 in 1 000 000 worldwide. We report a middle childhood female born of second degree consanguineous marriage with limping gait with muscle weakness, with normal development and IQ. Examination revealed microcornea, distal joint laxity of fingers and wrist, hypotonia and broad-based limping gait. Fracture dislocation right hip was managed by fixation. With the atypical neuroimaging finding of cerebellar vermis hypoplasia, exome sequencing was ordered and confirmed as Ehlers-Danlos syndrome (musculocontractural type-1). Hence, genetic counselling was done and prognosis of the child was explained.
Foundation models in ophthalmology
Authors: Chia Mark A , Antaki Fares , Zhou Yukun , Turner Angus W , Lee Aaron Y , Keane Pearse A
Published: June 2024

Foundation models represent a paradigm shift in artificial intelligence (AI), evolving from narrow models designed for specific tasks to versatile, generalisable models adaptable to a myriad of diverse applications. Ophthalmology as a specialty has the potential to act as an exemplar for other medical specialties, offering a blueprint for integrating foundation models broadly into clinical practice. This review hopes to serve as a roadmap for eyecare professionals seeking to better understand foundation models, while equipping readers with the tools to explore the use of foundation models in their own research and practice. We begin by outlining the key concepts and technological advances which have enabled the development of these models, providing an overview of novel training approaches and modern AI architectures. Next, we summarise existing literature on the topic of foundation models in ophthalmology, encompassing progress in vision foundation models, large language models and large multimodal models. Finally, we outline major challenges relating to privacy, bias and clinical validation, and propose key steps forward to maximise the benefit of this powerful technology.
Identifying subtypes of type 2 diabetes mellitus with machine learning: development, internal validation, prognostic validation and medication burden in linked electronic health records in 420 448 individuals
Authors: Mizani Mehrdad A , Dashtban Ashkan , Pasea Laura , Zeng Qingjia , Khunti Kamlesh , Valabhji Jonathan , Mamza Jil Billy , Gao He , Morris Tamsin , Banerjee Amitava
Published: June 2024

Introduction

None of the studies of type 2 diabetes (T2D) subtyping to date have used linked population-level data for incident and prevalent T2D, incorporating a diverse set of variables, explainable methods for cluster characterization, or adhered to an established framework. We aimed to develop and validate machine learning (ML)-informed subtypes for type 2 diabetes mellitus (T2D) using nationally representative data.

Research design and methods

In population-based electronic health records (2006–2020; Clinical Practice Research Datalink) in individuals ≥18 years with incident T2D (n=420 448), we included factors (n=3787), including demography, history, examination, biomarkers and medications. Using a published framework, we identified subtypes through nine unsupervised ML methods (K-means, K-means++, K-mode, K-prototype, mini-batch, agglomerative hierarchical clustering, Birch, Gaussian mixture models, and consensus clustering). We characterized clusters using intracluster distributions and explainable artificial intelligence (AI) techniques. We evaluated subtypes for (1) internal validity (within dataset; across methods); (2) prognostic validity (prediction for 5-year all-cause mortality, hospitalization and new chronic diseases); and (3) medication burden.

Results

Development: We identified four T2D subtypes: metabolic, early onset, late onset and cardiometabolic.Internal validity: Subtypes were predicted with high accuracy (F1 score >0.98).Prognostic validity: 5-year all-cause mortality, hospitalization, new chronic disease incidence and medication burden differed across T2D subtypes. Compared with the metabolic subtype, 5-year risks of mortality and hospitalization in incident T2D were highest in late-onset subtype (HR 1.95, 1.85–2.05 and 1.66, 1.58–1.75) and lowest in early-onset subtype (1.18, 1.11–1.27 and 0.85, 0.80–0.90). Incidence of chronic diseases was highest in late-onset subtype and lowest in early-onset subtype.Medications: Compared with the metabolic subtype, after adjusting for age, sex, and pre-T2D medications, late-onset subtype (1.31, 1.28–1.35) and early-onset subtype (0.83, 0.81–0.85) were most and least likely, respectively, to be prescribed medications within 5 years following T2D onset.

Conclusions

In the largest study using ML to date in incident T2D, we identified four distinct subtypes, with potential future implications for etiology, therapeutics, and risk prediction.
Teen pregnancy involvement among African, Caribbean and Black adolescent boys and girls: A scoping review
Authors: Ojukwu Emmanuela , Bawafaa Eunice , McKay Emily , Grewal Harsimran , Afsah Sara , Singh Shivangi , Saewyc Elizabeth
Published: June 2024

Objectives

This study aims to investigate the incidence, associated factors and interventions to address teen pregnancy involvement (TPI) among African, Caribbean and Black (ACB) adolescents in North America.

Design

We conducted a scoping review of the literature, guided by the social-ecological model.

Data sources

Studies were retrieved from databases such as Ovid Medline, Ovid Embase, CINAHL, CAB Direct and Google Scholar and imported into COVIDENCE for screening.

Eligibility criteria

The Joanna Briggs Institute scoping reviews protocol guided the establishment of eligibility criteria. Included studies focused on rates, associated factors and interventions related to TPI among ACB boys and girls aged 10–19 in North America. The publication time frame was restricted to 2010–2023, encompassing both peer-reviewed and non-peer-reviewed studies with diverse settings.

Data extraction and synthesis

Data were extracted from 32 articles using a form developed by the principal author, focusing on variables aligned with the research question.

Results

The scoping review revealed a dearth of knowledge in Canadian and other North American literature on TPI in ACB adolescents. Despite an overall decline in teen pregnancy rates, disparities persist, with interventions such as postpartum prescription of long-acting birth control and teen mentorship programmes proving effective.

Conclusion

The findings highlight the need for increased awareness, research and recognition of male involvement in adolescent pregnancies. Addressing gaps in housing, employment, healthcare, sexual health education and health systems policies for marginalised populations is crucial to mitigating TPI among ACB adolescents.

Impact

The review underscores the urgent need for more knowledge from other North American countries, particularly those with growing ACB migrant populations.
Morbidity and trends in length of hospitalisation of very and extremely preterm infants born between 2008 and 2021 in the Netherlands: a cohort study
Authors: de Bijl-Marcus Karen , Benders Manon J N L , Dudink Jeroen , Ahaus Kees , Kahlmann Marijn , Groenendaal Floris
Published: June 2024

Objectives

This study investigated changes in the length of stay (LoS) at a level III/IV neonatal intensive care unit (NICU) and level II neonatology departments until discharge home for very preterm infants and identified factors influencing these trends.

Design

Retrospective cohort study based on data recorded in the Netherlands Perinatal Registry between 2008 and 2021.

Setting

A single level III/IV NICU and multiple level II neonatology departments in the Netherlands.

Participants

NICU-admitted infants (n=2646) with a gestational age (GA) <32 weeks.

Main outcome measures

LoS at the NICU and overall LoS until discharge home.

Results

The results showed an increase of 5.1 days (95% CI 2.2 to 8, p<0.001) in overall LoS in period 3 after accounting for confounding variables. This increase was primarily driven by extended LoS at level II hospitals, while LoS at the NICU remained stable. The study also indicated a strong association between severe complications of preterm birth and LoS. Treatment of infants with a lower GA and more (severe) complications (such as severe retinopathy of prematurity) during the more recent periods may have increased LoS.

Conclusion

The findings of this study highlight the increasing overall LoS for very preterm infants. LoS of very preterm infants is presumably influenced by the occurrence of complications of preterm birth, which are more frequent in infants at a lower gestational age.
An exploratory open-label multicentre phase I/II trial evaluating the safety and efficacy of postnatal or prenatal and postnatal administration of allogeneic expanded fetal mesenchymal stem cells for the treatment of severe osteogenesis imperfecta in infants and fetuses: the BOOSTB4 trial protocol
Authors: Sagar Rachel L , Åström Eva , Chitty Lyn S , Crowe Belinda , David Anna L , DeVile Catherine , Forsmark Annabelle , Franzen Vera , Hermeren Göran , Hill Melissa , Johansson Mats , Lindemans Caroline , Lindgren Peter , Nijhuis Wouter , Oepkes Dick , Rehberg Mirko , Sahlin Nils-Eric , Sakkers Ralph , Semler O , Sundin Mikael , Walther-Jallow Lilian , Verweij E J T Joanne , Westgren Magnus , Götherström Cecilia
Published: June 2024

Introduction

Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4.

Methods and analysis

BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1–5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution inCOL1A1orCOL1A2can be included in the trial.

Each subject receives four intravenous doses of 3×106/kg BOOST cells at 4 month intervals, with 48 (doses 1–2) or 24 (doses 3–4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally.

The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover.

Ethics and dissemination

The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals.

Trial registration numbers

EudraCT 2015-003699-60, EUCT: 2023-504593-38-00,NCT03706482.
Assessing the association between a sedentary lifestyle and prevalence of primary osteoporosis: a community-based cross-sectional study among Chinese population
Authors: Wang Xiao-Song , Chen Yong , Zhao Yun-Wu , Chen Ming-Wei , Wang Heng
Published: June 2024

Objectives

To reveal the association between a sedentary lifestyle and the prevalence of primary osteoporosis (POP).

Design

A community-based cross-sectional study was conducted.

Setting

This study was conducted in communities in Hefei city, Anhui province, China.

Participants

A total of 1346 residents aged 40 and above underwent POP screening via calcaneus ultrasound bone mineral density (BMD) testing and completed a questionnaire survey.

Outcome measures

The average daily sitting time was included in the study variable and used to assess sedentary behaviour. The 15 control variables included general information, dietary information and life behaviour information. Logistic regression was used to analyse the association between the POP prevalence and study or control variables in different models.

Results

1346 participants were finally included in the study. According to the 15 control variables, the crude model and 4 models were established. The analysis revealed that the average daily sitting time showed a significant correlation with the prevalence of POP in the crude model (OR=2.02, 95% CI=1.74 to 2.36, p<0.001), Model 1 (OR=2.65, 95% CI=2.21 to 3.17, p<0.001), Model 2 (OR=2.63, 95% CI=2.19 to 3.15, p<0.001), Model 3 (OR=2.62, 95% CI=2.18 to 3.15, p<0.001) and Model 4 (OR=2.58, 95% CI=2.14 to 3.11, p<0.001). Besides, gender, age and body mass index showed a significant correlation with the POP prevalence in all models.

Conclusions

This study suggests a potential association between a sedentary lifestyle and the prevalence of POP within the Chinese population. Modifying sedentary behaviours could contribute to a reduction in POP risk. However, longitudinal cohort studies are necessary to confirm this hypothesis in the future.
Group arts therapies for patients with schizophrenia: a protocol of systematic review and meta-analysis
Authors: Zhang Aijia , Luo Xuexing , Lin Runqing , He Caihong , Wang Jue , Huang Guanghui
Published: June 2024

Introduction

Schizophrenia, a chronic mental problem, significantly impacts cognition, emotion and social functioning. Conventional pharmacotherapy faces challenges including numerous side effects, low adherence to medication and substantial costs. In this context, group arts therapies (GATs) emerge as a promising complementary approach for symptom alleviation in schizophrenia patients. Nonetheless, the effectiveness and safety of GATs are yet to be firmly established. This study aims to systematically assess the therapeutic impact of all group-based artistic interventions as complementary treatments for schizophrenia, focusing on their potential benefits.

Methods and analysis

This study will search four English-language databases (PubMed, Web of Science, Cochrane Library and Embase), two Chinese databases (Wanfang Data and China National Knowledge Infrastructure) and three Korean databases (RISS, Korean Citation Index and DBpia) from their inception until October 2023. It will include all randomised controlled trials that compare GATs for schizophrenia with standard rehabilitation methods. The primary outcome is the improvement in patients’ positive and negative symptoms. Methodologies such as bias risk assessment, data synthesis, sensitivity analysis and subgroup analysis will be implemented using Review Manager V.5.4. Study results with high heterogeneity will be merged using a random-effects model (I2>50% or p<0.1). In cases where meta-analysis is not viable due to significant clinical and methodological heterogeneity, a qualitative summary of the findings will be provided.

Ethics and dissemination

The data used in this systematic review are anonymised, devoid of any private information, eliminating the requirement for ethical approval. Dissemination of the research findings will be conducted via peer-reviewed publications.

PROSPERO registration number

CRD42023471583.
Association between magnesium depletion score and chronic obstructive pulmonary disease risk: a secondary data analysis from NHANES
Authors: Wang Kai Jin , Chen Hong , Wang Jin , Wang Yang
Published: June 2024

Background and objective

The association between magnesium depletion score (MDS) and the risk of chronic obstructive pulmonary disease (COPD) has not been examined to date. Meanwhile, the potential impact of dietary magnesium intake on this association remains unclear. This study aimed to investigate the influence of dietary magnesium intake on the association between MDS and COPD incidence.

Methods

In this cross-sectional study using the National Health and Nutrition Examination Survey database, we analysed the relationship between MDS and COPD, while also exploring the role of dietary magnesium.

Results

A total of 39 852 participants, including 1762 patients with COPD and 38 090 patients with non-COPD, were included in the analysis. After adjusting for confounding factors, our results demonstrated a significant association between higher MDS and increased COPD incidence (OR=1.48, 95% CI: 1.10 to 1.99). Furthermore, it was observed that dietary magnesium intake did not significantly impact this association.

Conclusion

This study highlights a significant positive correlation between MDS and the incidence of COPD. Nonetheless, no significant alteration in this association was observed with dietary magnesium intake.
Influence of the COVID-19 pandemic on births and induced abortions in Southern Sweden: a register-based study
Authors: Thacher Jesse D , Vilhelmsson Andreas , Blomberg Annelise J , Rylander Lars , Jöud Anna , Schmidt Lone , Hougaard Charlotte Ørsted , Elmerstig Eva , Vassard Ditte , Mattsson Kristina
Published: June 2024

Background

Pandemics are linked with declining birth rates, but little is known about how the COVID-19 pandemic has influenced childbearing decisions. We aimed to investigate the associations between the COVID-19 pandemic and reproductive decisions, specifically to identify potential changes in the frequency of deliveries and induced abortions in Skåne, Sweden.

Methods

Using the Skåne Healthcare Register, we identified women aged 15–45 years who had at least one pregnancy-related care visit registered between 1 January 2013 and 11 November 11 2021. Deliveries and induced abortions were identified, and changes in weekly delivery and abortion counts were assessed using an interrupted time series design. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated from a Poisson regression model.

Results

During the study period we identified 129 131 deliveries and 38 591 abortions. Compared with the counterfactual (exposed interval assuming COVID-19 had not occurred), pandemic exposure was associated with fewer deliveries (RR 0.93; 95% CI 0.89 to 0.98). For abortions, pandemic exposure appeared to be associated with fewer abortions (RR 0.95; 95% CI 0.90 to 1.00); however, age-related differences were found. Among women aged 25 years and over, pandemic exposure was more strongly associated with fewer abortions. Contrastingly, among women aged under 25 years, abortions appeared to increase.

Conclusions

The COVID-19 pandemic seemed to have contributed to a decline in births in Southern Sweden. During the same period, abortions declined in women in the older age range, but contrastingly increased among younger women.
Psychometric validation of a patient-reported experience measure for older adults attending the emergency department: the PREM-ED 65 study
Authors: Graham Blair , Smith Jason E , Wei Yinghui , Nelmes Pamela , Latour Jos M
Published: June 2024

Introduction

Optimising emergency department (ED) patient experience is vital to ensure care quality. However, there are few validated instruments to measure the experiences of specific patient groups, including older adults. We previously developed a draft 82-item Patient Reported Experience Measure (PREM-ED 65) for adults ≥65 attending the ED. This study aimed to derive a final item list and provide initial validation of the PREM-ED 65 survey.

Methods

A cross-sectional study involving patients in 18 EDs in England. Adults aged 65 years or over, deemed eligible for ED discharge, were recruited between May and August 2021 and asked to complete the 82-item PREM at the end of the ED visit and 7–10 days post discharge. Test–retest reliability was assessed 7—10 days following initial attendance. Analysis included descriptive statistics, including per-item proportions of responses, hierarchical item reduction, exploratory factor analysis (EFA), reliability testing and assessment of criterion validity.

Results

Five hundred and ten initial surveys and 52 retest surveys were completed. The median respondent age was 76. A similar gender mix (men 47.5% vs women 50.7%) and reason for attendance (40.3% injury vs 49.0% illness) was observed. Most participants self-reported their ethnicity as white (88.6%).

Hierarchical item reduction identified 53/82 (64.6%) items for exclusion, due to inadequate engagement (n=33), ceiling effects (n=5), excessive inter-item correlation (n=12) or significant differential validity (n=3). Twenty-nine items were retained.

EFA revealed 25 out of the 29 items demonstrating high factor loadings (>0.4) across four scales with an Eigenvalue >1. These scales were interpreted as measuring ‘relational care’, ‘the ED environment’, ‘staying informed’ and ‘pain assessment’. Cronbach alpha for the scales ranged from 0.786 to 0.944, indicating good internal consistency. Test–retest reliability was adequate (intraclass correlation coefficient 0.67). Criterion validity was fair (r=0.397) when measured against the Friends and Families Test question.

Conclusions

Psychometric testing demonstrates that the 25-item PREM-ED 65 is suitable for administration to adults ≥65 years old up to 10 days following ED discharge.