bluuebunny/crossref_metadata_2025 huggingface dataset:
Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation
Authors: Juyoux Pauline , Galdadas Ioannis , Gobbo Dorothea , von Velsen Jill , Pelosse Martin , Tully Mark , Vadas Oscar , Gervasio Francesco Luigi , Pellegrini Erika , Bowler Matthew W.
Published: September 2023

The mitogen-activated protein kinase (MAPK) p38α is a central component of signaling in inflammation and the immune response and is, therefore, an important drug target. Little is known about the molecular mechanism of its activation by double phosphorylation from MAPK kinases (MAP2Ks), because of the challenge of trapping a transient and dynamic heterokinase complex. We applied a multidisciplinary approach to generate a structural model of p38α in complex with its MAP2K, MKK6, and to understand the activation mechanism. Integrating cryo–electron microscopy with molecular dynamics simulations, hydrogen-deuterium exchange mass spectrometry, and experiments in cells, we demonstrate a dynamic, multistep phosphorylation mechanism, identify catalytically relevant interactions, and show that MAP2K-disordered amino termini determine pathway specificity. Our work captures a fundamental step of cell signaling: a kinase phosphorylating its downstream target kinase.
Four governance reforms to strengthen the SDGs
Authors: Biermann Frank , Sun Yixian , Banik Dan , Beisheim Marianne , Bloomfield Michael J. , Charles Aurelie , Chasek Pamela , Hickmann Thomas , Pradhan Prajal , Sénit Carole-Anne
Published: September 2023

A demanding policy vision can accelerate global sustainable development efforts
Chemically fueling new microrobot abilities
Authors: Truby Ryan L.
Published: September 2023

A combustion-powered soft actuator takes microrobots to new heights and speeds
As artificial intelligence goes multimodal, medical applications multiply
Authors: Topol Eric J.
Published: September 2023

Machines don’t have eyes, but you wouldn’t know that if you followed the progression of deep learning models for accurate interpretation of medical images, such as x-rays, computed tomography (CT) and magnetic resonance imaging (MRI) scans, pathology slides, and retinal photos. Over the past several years, there has been a torrent of studies that have consistently demonstrated how powerful “machine eyes“ can be, not only compared with medical experts but also for detecting features in medical images that are not readily discernable by humans. For example, a retinal scan is rich with information that people can’t see, but machines can, providing a gateway to multiple aspects of human physiology, including blood pressure; glucose control; risk of Parkinson’s, Alzheimer’s, kidney, and hepatobiliary diseases; and the likelihood of heart attacks and strokes. As a cardiologist, I would not have envisioned that machine interpretation of an electrocardiogram would provide information about the individual’s age, sex, anemia, risk of developing diabetes or arrhythmias, heart function and valve disease, kidney, or thyroid conditions. Likewise, applying deep learning to a pathology slide of tumor tissue can also provide insight about the site of origin, driver mutations, structural genomic variants, and prognosis. Although these machine vision capabilities for medical image interpretation may seem impressive, they foreshadow what is potentially far more expansive terrain for artificial intelligence (AI) to transform medicine. The big shift ahead is the ability to transcend narrow, unimodal tasks, confined to images, and broaden machine capabilities to include text and speech, encompassing all input modes, setting the foundation for multimodal AI.
In Science Journals
Authors: Scanlon Seth Thomas , Hurtley Stella M. , Vignieri Sacha , Maroso Mattia , Funk Michael A. , Baek Amy E. , Suleymanov Yury , Smith Orla M. , Lempriere Sarah A. , Kelly Priscilla N. , Lavine Marc S. , Olingy Claire
Published: September 2023

Highlights from the
Science
family of journals
U.K. finally rejoins Horizon Europe
Authors: O’Grady Cathleen
Published: September 2023

After years of excruciating delays, elated scientists welcome research funding agreement
U.S. kills effort to hunt dangerous viruses
Authors: Cohen Jon
Published: September 2023

Critics feared DEEP VZN project could help pathogens jump from animals to humans
Listeria monocytogenes
folate metabolism is required to generate N-formylmethionine during infection
Authors: Tang Qing , Reniere Michelle L.
Published: September 2023

Folic acid and its derivatives are required for the synthesis of purines, pyrimidines, and some amino acids. Antifolate antibiotics that target the folic acid metabolism pathway are commonly used for the treatment of listeriosis caused by the intracellular pathogen
Listeria monocytogenes
(
Lm
). In recent work in
mBio
, Feng et al. sought to understand the role of folic acid metabolism in
Lm
virulence (Y. Feng, S. Chang, D. A. Portnoy, 2023, mBio
https://doi.org/10.1128/mbio.01074-23
). The authors discovered that N-formylmethionine, an amino acid utilized by bacteria to initiate protein synthesis, is crucial for
Lm
intracellular growth and pathogenesis. Surprisingly, purines and thymidine were found to be dispensable for
Lm
infection. Together these results demonstrate that while
Lm
can obtain many essential nutrients from the host cytosol, including purines and most amino acids, it requires N-formylmethionine biosynthesis to properly regulate translation initiation during infection.
The novel spore-specific regulator SscA controls
Aspergillus
conidiogenesis
Authors: Son Ye-Eun , Yu Jae-Hyuk , Park Hee-Soo
Published: September 2023

A major group of fungi produces asexual spores (conidia) for dissemination and propagation and, in pathogenic fungi, for infection. Despite the critical role of conidia, the underlying mechanism of spore formation, integrity, and viability is not fully elucidated. In this study, we have identified and investigated the roles of the spore-specific transcription factor (TF) SscA in three
Aspergillus
species, including
A. nidulans
,
A. flavus
, and
A. fumigatus,
which is a model system, toxin producer, or a prevalent human pathogen, respectively. Comparative transcriptomic analyses have revealed that 25 TF encoding genes showed higher mRNA levels in conidia than in hyphae in three species. Functional analyses of the 25 genes have identified SscA as a key TF for conidial formation, maturation, germination, integrity, amino acid production, and secondary metabolism in
Aspergillus nidulans
conidia. Importantly, the roles of SscA are conserved in other
Aspergillus
species. Altogether, our study demonstrates that SscA is a spore-specific TF that governs the production of intact and functional conidial formation in
Aspergillus
species.

IMPORTANCE

Filamentous fungi produce myriads of asexual spores, which are the main reproductive particles that act as infectious or allergenic agents. Although the serial of asexual sporogenesis is coordinated by various genetic regulators, there remain uncharacterized transcription factors in
Aspergillus
. To understand the underlying mechanism of spore formation, integrity, and viability, we have performed comparative transcriptomic analyses on three
Aspergillus
species and found a spore-specific transcription factor, SscA. SscA has a major role in conidial formation, maturation and dormancy, and germination in
Aspergillus nidulans
. Functional studies indicate that SscA coordinates conidial wall integrity, amino acid production, and secondary metabolism in
A. nidulans
conidia. Furthermore, the roles of SscA are conserved in other
Aspergillus
species. Our findings that the SscA has broad functions in
Aspergillus
conidia will help to understand the conidiogenesis of
Aspergillus
species.
Characterization of two novel VIM-type metallo-β-lactamases, VIM-84 and VIM-85, associated with the spread of IncP-2 megaplasmids in
Pseudomonas aeruginosa
Authors: Wang Nanfei , Lei Tailong , Zhu Yiwei , Li Yue , Cai Heng , Zhang Piaopiao , Leptihn Sebastian , Zhou Junxin , Ke Huanhuan , Gao Bo , Feng Yu , Hua Xiaoting , Qu Tingting
Published: September 2023

This study aimed to characterize two novel VIM-type metallo-β-lactamases, VIM-84 and VIM-85, and reveal the important role of the IncP-2 type megaplasmids in the spread of antimicrobial resistance (AMR) genes. VIM-84 and VIM-85 were encoded by two novel genes
bla
VIM-84
and
bla
VIM-85
which showed similarity to
bla
VIM-24
. Both
bla
VIM-84
and
bla
VIM-85
are harbored into class 1 integrons embedded into the Tn
1403
transposon. The
bla
VIM-85
gene was identified in a megaplasmid, which was related to 17 megaplasmid sequences with sizes larger than 430 kb, deposited previously in Genbank. A comparative analysis of complete plasmid sequences showed highly similar backbone regions and various AMR genes. A phylogenetic tree revealed that these megaplasmids, which were widely distributed globally, were vehicles for the spread of AMR genes. The
bla
VIM-24
,
bla
VIM-84
, and
bla
VIM-85
genes were cloned into pGK1900, and the recombinant vectors were further transformed into
Escherichia coli
DH5α and
Pseudomonas aeruginosa
PAO1. The antimicrobial susceptibility test of the cloning strains showed high levels of resistance to β-lactams while they remained susceptible to aztreonam. Enzymatic tests revealed that both, VIM-84 and VIM-85, exhibited higher activity in hydrolyzing β-lactams compared to VIM-24. A D117N mutation found in VIM-24 affected binding to the antibiotics.

IMPORTANCE

The metallo-β-lactamases-producing
Pseudomonas aeruginosa
strains play an important role in hospital outbreaks and the VIM-type enzyme is the most prevalent in European countries. Two novel VIM-type enzymes in our study, VIM-84 and VIM-85, have higher levels of resistance to β-lactams and greater hydrolytic activities for most β-lactams compared with VIM-24. Both
bla
VIM-84
and
bla
VIM-85
are harbored into class 1 integrons embedded into the Tn
1403
transposon. Notably, the genes
bla
VIM-85
are carried by three different IncP-2-type megaplasmids which are distributed locally and appear responsible for the spread of antimicrobial resistance genes in hospital settings.
Secreted NS1 proteins of tick-borne encephalitis virus and West Nile virus block dendritic cell activation and effector functions
Authors: Camarão António A. R. , Gern Olivia Luise , Stegmann Felix , Mulenge Felix , Costa Bibiana , Saremi Babak , Jung Klaus , Lepenies Bernd , Kalinke Ulrich , Steffen Imke
Published: September 2023

The flavivirus non-structural protein 1 (NS1) is secreted from infected cells into the circulation and the serum levels correlate with disease severity. The effect of secreted NS1 (sNS1) on non-infected mammalian immune cells is largely unknown. Here, we expressed recombinant sNS1 proteins of tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) and investigated their effects on dendritic cell (DC) effector functions. Murine bone marrow-derived DCs (BMDCs) showed reduced surface expression of co-stimulatory molecules and decreased release of pro-inflammatory cytokines when treated with sNS1 of TBEV or WNV prior to poly(I:C) stimulation. Transcriptional profiles of BMDCs that were sNS1-exposed prior to poly(I:C) stimulation showed two gene clusters that were downregulated by TBEV or WNV sNS1 and that were associated with innate and adaptive immune responses. Functionally, both sNS1 proteins modulated the capacity for BMDCs to induce specific T-cell responses as indicated by reduced IFN-γ levels in both CD4
+
and CD8
+
T cells after BMDC co-cultivation. In human monocyte-derived DCs, poly(I:C)-induced upregulation of co-stimulatory molecules and cytokine responses were even more strongly impaired by TBEV sNS1 or WNV sNS1 pretreatment than in the murine system. Our findings indicate that exogenous flaviviral sNS1 proteins interfere with DC-mediated stimulation of T cells, which is crucial for the initiation of cell-mediated adaptive immune responses in human flavivirus infections. Collectively, our data determine soluble flaviviral NS1 as a virulence factor responsible for a dampened immune response to flavivirus infections.

IMPORTANCE

The effective initiation of protective host immune responses controls the outcome of infection, and dysfunctional T-cell responses have previously been associated with symptomatic human flavivirus infections. We demonstrate that secreted flavivirus NS1 proteins modulate innate immune responses of uninfected bystander cells. In particular, sNS1 markedly reduced the capacity of dendritic cells to stimulate T-cell responses upon activation. Hence, by modulating cellular host responses that are required for effective antigen presentation and initiation of adaptive immunity, sNS1 proteins may contribute to severe outcomes of flavivirus disease.
Biotransformation of protein-rich waste by
Yarrowia lipolytica
IPS21 to high-value products—amino acid supernatants
Authors: Wieczorek Dorota , Gendaszewska Dorota , Miśkiewicz Katarzyna , Słubik Anna , Ławińska Katarzyna
Published: September 2023

The yeast strain
Yarrowia lipolytica
IPS 21 was tested for its ability to degrade potentially toxic chrome-tanned leather shavings (CTLS) in a liquid environment. Biological and chemical parameters were monitored during a 48-h period of biotransformation of the protein-rich waste. CTLS was added at a concentration of 0.1–4% (wt/wt) to a modified YPG medium (15 g L
−1
yeast extract and 5 g L
−1
NaCl). Biodegradation and bioconversion were performed in a one-step process. It was found that the higher degradation rate depended on the activity of the proteases and the pH of the medium, but not on the initial inoculum ratio and the activity of the dehydrogenase. The highest efficiency of the process was obtained for 4% (wt/wt) CTLS on day 2 (degradation rate 58–67%, biomass production 2.11–2.20 g L
−1
, protease activity 312 U mg
−1
protein, and pH 9.20). Our results showed that total chromium was probably not transported across the cytoplasmic membrane of
Y. lipolytica
IPS21 and that chromium (III) was not oxidized to chromium (VI). The phytotoxicity of selected amino acid supernatants [2.5% (vol/vol)] was tested after the bioconversion process. It was found that the supernatants had a stimulating effect on the plants tested. The root elongation was 29–28% higher than that of the reference samples. This result makes
Y. lipolytica
IPS21 a potential candidate for safely converting potentially toxic protein-rich wastes into valuable products without enzyme isolation, e.g., amino acid fertilizers.

IMPORTANCE

Enzyme technologies have the greatest practical relevance to environmental trends. Overcoming the barrier of the high cost of carbon substrates used for biotransformation is the main challenge of these methods. The huge potential of the use of extracellular proteases of
Yarrowia
species or amino acids in various industries indicates the need for the extension of basic research on waste as a carbon source for this yeast. The experiments demonstrated that it is possible to use
Y. lipolytica
IPS21 for bioconversion of chrome-tanned leather shavings (CTLS) in a single-step process and to produce high-value amino acid supernatant without having an isolated enzyme. In our study, we show the effect of 2.5% (vol/vol) CTLS supernatant obtained from
Y. lipolytica
IPS21 on the elongation of the root system of selected plants and provide information on the effect of environmental factors on the efficiency of the bioconversion and the migration of chromium.
ATG9A supports
Chlamydia trachomatis
infection via autophagy-independent mechanisms
Authors: Suzuki Michitaka , Funakoshi Tomoko , Kumagai Keigo , Komatsu Masaaki , Waguri Satoshi
Published: September 2023

Chlamydia trachomatis
infection can be regulated by autophagy-related (
ATG
) genes. Here, we found that the depletion of
ATG9A
, one of the core
ATG
genes, in HeLa cells suppressed
C. trachomatis
growth in the inclusion. The growth was restored by re-expressing
ATG9A
or an
ATG9A
mutant impairing lipid scramblase activity in
ATG9A
-knockout (KO) cells. Moreover, the depletion of lipid transfer proteins ATG2A/B, responsible for isolation membrane expansion together with ATG9A, did not significantly alter the growth, suggesting that the non-autophagic function of ATG9A supports
C. trachomatis
infection.
ATG9A
-KO cells showed no infection-induced redistribution of the Golgi from the perinuclear region to inclusion, which was restored by re-expressing the mutant but not the
ATG9A
mutant lacking an N-terminal adapter protein-binding domain. Re-expression of the N-terminal deletion mutant in
ATG9A
-KO cells did not rescue
C. trachomatis
growth, suggesting the importance of this domain for its growth. Although
ATG9A
-KO cells showed enhanced TBK1 activation, interferon (IFN)-β was not significantly increased, excluding the possibility that upregulation of stimulator of IFN genes (STING) signaling suppressed bacterial growth. Taken together, these findings suggest that the proper trafficking, rather than the isolation membrane expansion function, of ATG9A assists
C. trachomatis
growth in the inclusion.

IMPORTANCE

ATG9A
is an autophagy-related gene that functions during the isolation membrane expansion process to form autophagosomes, but it also has other functions independent of autophagy. In this study, we employed
ATG9A
-deficient HeLa cells and found that the absence of
ATG9A
negatively impacted proliferation of
Chlamydia trachomatis
in inclusions. Furthermore, rescue experiments using
ATG9A
mutants revealed that this action was mediated not by its autophagic function but by its binding ability to clathrin adapter proteins. These findings suggest that the proper trafficking of ATG9A assists
C. trachomatis
growth in the inclusion.
Kinetic, genomic, and physiological analysis reveals diversity in the ecological adaptation and metabolic potential of
Brachybacterium equifaecis
sp. nov. isolated from horse feces
Authors: Farooq Adeel , Lee Myunglip , Han Saem , Jung Gi-Yong , Kim So-Jeong , Jung Man-Young
Published: September 2023

Brachybacterium species have been identified in various ecological niches and belong to the family
Dermabacteriaceae
within the phylum
Actinobacteria
. In this study, we isolated a novel
Brachybacterium equifaecis
JHP9 strain from horse feces and compared its kinetic, biochemical, and genomic features with those of other
Brachybacterium
strains. Moreover, comparative genomic analysis using publicly available
Brachybacterium
genomes was performed to determine the properties involved in their ecological adaptation and metabolic potential. Novel species delineation was determined phylogenetically through 16S rRNA gene similarity (up to 97.9%), average nucleotide identity (79.5–82.5%), average amino acid identity (66.7–75.8%), and
in silico
DNA-DNA hybridization (23.7–27.9) using closely related strains. This study also presents the first report of the kinetic properties of
Brachybacterium
species. Most of the
Brachybacterium
strains displayed high oxygen (
K
m(app)
=1.6–24.2 µM) and glucose (
K
m(app)
=0.73–1.22 µM) affinities, which may manifest niche adaptations. Various carbohydrate metabolisms under aerobic and anaerobic conditions, antibiotic resistance, mobile genetic elements, carbohydrate-active enzymes, lactic acid production, and the clustered regularly interspaced short palindromic repeats-Cas and bacteriophage exclusion systems were observed in the genotypic and/or phenotypic properties of
Brachybacterium
species, suggesting their genome flexibility, defense mechanisms, and adaptability. Our study contributes to the knowledge of the kinetic, physiological, and genomic properties of
Brachybacterium
species, including the novel JHP9 strain, which advocates for their tolerant and thriving nature in various environments, leading to their ecological adaptation.

IMPORTANCE

Basic physiological and genomic properties of most of the
Brachybacterium
isolates have been studied; however, the ability of this bacterium to adapt to diverse environments, which may demonstrate its role in niche differentiation, is to be identified yet. Therefore, here, we explored cellular kinetics, metabolic diversity, and ecological adaptation/defensive properties of the novel
Brachybacterium
strain through physiological and comparative genomic analysis. In addition, we presented the first report examining
Brachybacterium
kinetics, indicating that all strains of
Brachybacterium
, including the novel one, have high oxygen and glucose affinity. Furthermore, the comparative genomic analysis also revealed that the novel bacterium contains versatile genomic properties, which provide the novel bacterium with significant competitive advantages. Thus, in-depth genotypic and phenotypic analysis with kinetic properties at the species level of this genus is beneficial in clarifying its differential characteristics, conferring the ability to inhabit diverse ecological niches.
CRISPR-based tools for targeted genetic manipulation in pathogenic
Sporothrix
species
Authors: Hatinguais Remi , Leaves Ian , Brown Gordon D. , Brown Alistair J. P. , Brock Matthias , Peres da Silva Roberta
Published: September 2023

Sporothrix brasiliensis
is an emerging fungal pathogen frequently associated with zoonotic transmission of sporotrichosis by contaminated cats. Within 25 years, the disease has spread not only throughout Brazil but now to neighboring countries in Latin America. Thermo-dimorphism, melanin, glycans, adhesins, and secreted vesicles have been associated with the ability of
Sporothrix
species to cause disease in the mammalian host. Although certain virulence factors have been proposed as potential determinants for sporotrichosis, the scarcity of molecular tools for performing reverse genetics in
Sporothrix
has significantly impeded the dissection of mechanisms underlying the disease. Here, we demonstrate that PEG-mediated protoplast transformation is a powerful method for heterologous gene expression in
S. brasiliensis, S. schenckii,
and
S. chilensis
. Combined with CRISPR/Cas9 gene editing, this transformation protocol enabled the deletion of the putative DHN-melanin synthase gene
pks1
, which is a proposed virulence factor of
Sporothrix
species. To improve
in locus
integration of deletion constructs, we deleted the KU
80
homolog that is critical for non-homologous end-joining DNA repair. The use of Δ
ku80
strains from
S. brasiliensis
enhanced homologous-directed repair during transformation resulting in increased targeted gene deletion in combination with CRISPR/Cas9. In conclusion, our CRISPR/Cas9-based transformation protocol provides an efficient tool for targeted gene manipulation in
Sporothrix
species.

IMPORTANCE

Sporotrichosis caused by
Sporothrix brasiliensis
is a disease that requires long periods of treatment and is rapidly spreading across Latin America. The virulence of this fungus and the surge of atypical and more severe presentations of the disease raise the need for an understanding of the molecular mechanisms underlying sporotrichosis, as well as the development of better diagnostics and antifungal therapies. By developing molecular tools for accurate genetic manipulation in
Sporothrix,
this study addresses the paucity of reliable and reproducible tools for stable genetic engineering of
Sporothrix
species, which has represented a major obstacle for studying the virulence determinants and their roles in the establishment of sporotrichosis.
Neurodevelopmental outcomes at age 3 years after moderate preterm, late preterm and early term birth: the Japan Environment and Children’s Study
Authors: Hirata Katsuya , Ueda Kimiko , Wada Kazuko , Ikehara Satoyo , Tanigawa Kanami , Kimura Tadashi , Ozono Keiichi , Sobue Tomotaka , Iso Hiroyasu
Published: September 2023

Objective

To assess the association between gestational age classification at birth and the risk of neurodevelopmental impairments at age 3 years.

Design

Cohort study using the Japan Environment and Children’s Study database.

Patients

A total of 86 138 singleton children born without physical abnormalities at 32–41 weeks of gestation enrolled between January 2011 and March 2014.

Main outcome measures

Neurodevelopmental impairment, evaluated using the Ages and Stages Questionnaire (third edition).

Methods

Logistic regression analysis was used to evaluate the risk of neurodevelopmental impairment in moderate preterm, late preterm and early term children compared with term children after adjusting for socioeconomic and perinatal factors.

Results

The respective adjusted ORs (95% CIs) of incidence of scores below the cut-off value (<−2.0 SD) at age 3 years for moderate preterm, late preterm and early term births, compared with full-term births, were as follows: communication, 2.40 (1.54 to 3.73), 1.43 (1.19 to 1.72) and 1.11 (1.01 to 1.21); gross motor, 2.55 (1.69 to 3.85), 1.62 (1.36 to 1.93) and 1.20 (1.10 to 1.30); fine motor, 1.93 (1.34 to 2.78), 1.55 (1.35 to 1.77) and 1.08 (1.01 to 1.15); problem solving, 1.80 (1.22 to 2.68), 1.36 (1.19 to 1.56) and 1.07 (1.00 to 1.14) and personal-social, 2.09 (1.29 to 3.40), 1.32 (1.07 to 1.63) and 1.00 (0.91 to 1.11).

Conclusion

Moderate preterm, late preterm and early term births were associated with developmental impairment at age 3 years compared with full-term births, with increasing prematurity. Careful follow-up of non-full-term children by paediatricians and other healthcare providers is necessary for early detection of neurodevelopmental impairment and implementation of available intervention.
Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study
Authors: Huhn Evelyn A , Göbl Christian S , Fischer Thorsten , Todesco Bernasconi Monya , Kreft Martina , Kunze Mirjam , Vogt Deborah R , Dölzlmüller Eva , Jaksch-Bogensperger Heidi , Heldstab Sandra , Eppel Wolfgang , Husslein Peter , Ochsenbein Kölble Nicole , Richter Anne , Bäz Elke , Winzeler Bettina , Hoesli Irene
Published: September 2023

Objective

To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values.

Design

International, prospective, multicentre cohort study.

Setting

Six university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019.

Participants

Low risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results.

Main outcome measures

Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation).

Results

Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31).

Conclusions

The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear.

Trial registration

ClinicalTrials.govNCT02035059.
Recurrence and return to duty following patellar instability events in military personnel
Authors: Abraham Vivek M , Wieschhaus K , Goldman A H , Balazs G C
Published: September 2023

Introduction

Military service members experience patellar dislocations at a rate 10 times that of civilians. The purpose of this study was to determine the return to duty rate of active duty military personnel following first-time or recurrent patellar dislocation. Secondary goals were to identify patient variables and radiographic parameters associated with recurrent instability and requiring medical separation from military service.

Methods

The Military Health System Data Repository was used to identify all active-duty military personnel who sustained a patellar dislocation between 2013 and 2018. Medical records were searched for patient variables including demographics, clinical findings, radiographic findings, treatment, adverse outcomes and military disposition. Patient variables associated with recurrent instability and undergoing medical separation were determined using univariate analysis and multivariate logistic regression. A total of 207 patients met inclusion and exclusion criteria.

Results

Following patellar instability event, 30% of the cohort underwent surgical treatment. Fourteen per cent (29 of 207) underwent medical separation from military service. Regardless of treatment, 9% (18 of 207) experienced recurrent dislocation and 3% (6 of 207) experienced recurrent instability without dislocation. On multivariate analysis, none of the studied patient variables were associated with recurrent instability or medical separation.

Conclusions

Among military personnel, return to duty rates are similar to return to sport rates in civilians. This study demonstrates no difference in risk of recurrent instability or medical separation based on anatomical factors, which is useful during shared decision-making regarding treatment options and goals.
Prognostic value of ultrasound tissue characterisation for a recurrence of mid-portion Achilles tendinopathy in military service members: a prospective cohort study
Authors: Paantjens M A , Helmhout P H , Backx F J G , Martens M T A W , Bakker E W P
Published: September 2023

Introduction

Tendon structure in mid-portion Achilles tendinopathy (mid-AT) appears poorly associated with symptoms. Yet, degenerative tendon changes on imaging have been associated with an increased risk of mid-AT. We aimed to investigate the prognostic value of ultrasound tissue characterisation (UTC) for a mid-AT recurrence in service members reporting to be recovered following standard care.

Methods

Mid-portion aligned fibrillar structure was quantified post-treatment in 37 participants. Recurrences were determined after 1 year of follow-up, based on self-perceived recurrence (yes/no) combined with a decrease in post-treatment Victorian Institute of Sports Assessment–Achilles score of at least the minimal important change of 7 points. Receiver operating characteristic curve analyses were used to determine a threshold for dichotomisation of outcomes for aligned fibrillar structure (normal representation/under-representation). Using multivariable logistic regression, the association between a mid-AT recurrence (yes/no) and the dichotomised aligned fibrillar structure was determined.

Results

Eight participants (22%) experienced a recurrence. The threshold for aligned fibrillar structure was set at 73.2% (95% CI: 69.4% to 77.8%) according to Youden’s index. Values below this threshold were significantly associated with a mid-AT recurrence (odds ratio (OR) 9.7, 95% CI: 1.007 to 93.185). The OR for a mid-AT recurrence was 1.1 (95% CI: 1.002 to 1.150) for each additional month of symptom duration. The explained variance of our multivariable logistic regression model was 0.423; symptom duration appeared to be a better predictor than aligned fibrillar structure.

Conclusions

This study identified mid-portion aligned fibrillar structure and symptom duration as potential prognostic factors for a mid-AT recurrence in military service members. The threshold for aligned fibrillar structure of 73.2% can guide preventative interventions (eg, training load adjustments or additional tendon load programmes) aiming to improve tendon structure to minimise the future recurrence risk.

Trial registration number

https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm, file number ToetsingOnline NL69527.028.19
Distinguishing between deterministic oscillations and noise
Authors: Rowland Adams Joe , Newman Julian , Stefanovska Aneta
Published: September 2023

Time-dependent dynamics is ubiquitous in the natural world and beyond. Effectively analysing its presence in data is essential to our ability to understand the systems from which it is recorded. However, the traditional framework for dynamics analysis is in terms of time-independent dynamical systems and long-term statistics, as opposed to the explicit tracking over time of time-localised dynamical behaviour. We review commonly used analysis techniques based on this traditional statistical framework—such as the autocorrelation function, power-spectral density, and multiscale sample entropy—and contrast to an alternative framework in terms of finite-time dynamics of networks of time-dependent cyclic processes. In time-independent systems, the net effect of a large number of individually intractable contributions may be considered as noise; we show that time-dependent oscillator systems with only a small number of contributions may appear noise-like when analysed according to the traditional framework using power-spectral density estimation. However, methods characteristic of the time-dependent finite-time-dynamics framework, such as the wavelet transform and wavelet bispectrum, are able to identify the determinism and provide crucial information about the analysed system. Finally, we compare these two frameworks for three sets of experimental data. We demonstrate that while techniques based on the traditional framework are unable to reliably detect and understand underlying time-dependent dynamics, the alternative framework identifies deterministic oscillations and interactions.
Making decisions based on multiple criteria in developing a league season teaching strategy for understanding playing functionalities
Authors: Shankar Harshitha Urs Aijipura , Nanjappa Udaya Kumara Kodipalya , Singh Sanjeet , Waqas M. , Elamin Khalda Mohamed Ahmed , Abdullaev Sherzod Shukhratovich , Govindan V.
Published: September 2023

In order to grasp the playing functions that utilize criteria for decision-making (DM) approaches, this paper offers a League season learning selection issue. The decision criteria to assess several game-based learning options are outlined, and a real-world choice dilemma is provided. Finding the most effective League season learning among playing functions is the goal. The needs for a League season of learning, such as Cognitive Methodologies, Gameplay Characteristics, Psychological Reactions, Accessibility, Users, as well as its environmental and societal impacts, are taken into consideration, leading to the identification of six primary criteria and 22 sub-criteria. Analytical Hierarchy Process (AHP) is used to calculate the criterion weights. The Preference Ranking Organization Method for Enrichment Evaluations and Vlse Kriterijumska Optimizacija I Kompromisno Resenje techniques are used to rank and choose between four possibilities. The outcomes of the Preference Ranking Organization Method for Enrichment Evaluations and Vlse Kriterijumska Optimizacija I Kompromisno Resenje procedures are also contrasted with those of the Complex Proportional Assessment, Multi-Atributive Ideal-Real Comparative Analysis and Multi-Attributive Border Approximation Area Comparison approaches. The results of the rankings of the alternatives produced by each approach all recommend the same choice as the best. Thus, it can be said that Preference Ranking Organization Method for Enrichment Evaluations, Vlse Kriterijumska Optimizacija I Kompromisno Resenje, Complex Proportional Assessment, Multi-Atributive Ideal-Real Comparative Analysis and Multi-Attributive Border Approximation Area Comparison approaches may be successfully employed for selection issues in game-based learning, as well as generally for other forms of multi-criteria decision problems with finite number of choices.
Impact of heat transfer on peristaltic flow of nanofluid and its applications in real world problems
Authors: Haider Jamil Abbas , Gul Sana , Gepreel Khaled A. , Khan Muhammad Naveed , Lone Showkat Ahmad
Published: September 2023

Nanofluids with peristaltic flows are being studied in depth because they can be used in so many different ways, such as to diagnose and treat diseases. In this paper, the peristaltic flow of a nanofluid with viscosity and electric conductivity that change with temperature is used. There are different base fluids and nanoparticles that are being thought about. First, the governing equations are modeled, and then they are made easier to understand by assuming that the wavelength is long and the Reynolds number is small. To make a dimensionless differential system, the right dimensionless numbers are added. Mathematica’s built-on function NDSolve is used to figure out the numerical solution of the resulting system. To figure out how fast heat moves, researchers compare different combinations of base fluids and nanoparticles.
Dephasing effects on quantum correlations and teleportation in presence of state dependent bath
Authors: Rashid Mehboob , Lone Muzaffar Qadir , Ganai Prince A.
Published: September 2023

Quantum information protocols are often designed in the ideal situation with no decoherence. However, in real setup, these protocols are subject to the decoherence and thus reducing fidelity of the measurement outcome. In this work, we analyze the effect of state-dependent bath on the quantum correlations and the fidelity of a single qubit teleportation. We model our system-bath interaction as qubits interacting with a common bath of bosons, and the state dependence of the bath is generated through a projective measurement on the joint state in thermal equilibrium. The analytic expressions for the time evolution of entanglement, discord and average fidelity of quantum teleportation are calculated. It is shown that due to the presence of initial system-bath correlations, the system maintains quantum correlations for long times. Furthermore, due to the presence of finite long-time entanglement of the quantum channel, the average fidelity is shown to be higher than its classical value.
Petal-like ZnO-based ultra-sensitive ethylene glycol sensors synthesized by solvent regulation
Authors: Zhang Qian-Qian , Ma Shu-Yi , Li Xiang-Bing , Yuan Fang-Qiang
Published: September 2023

The ZnO-10, ZnO-20, ZnO-30, and ZnO-40 nanopetal-shaped samples were successfully synthesized by a hydrothermal method. The results of XRD, SEM, TEM, and BET indicate that the micro–nano petal-like samples have the advantages of high purity, good crystallinity, and large specific surface area. The ZnO-20 sample with the largest specific surface area and pore volume was prepared by adjusting the scheme without changing the sample morphology. The specific surface area and pore volume of the sample were 33.6914[Formula: see text]m2/g and 0.1561[Formula: see text]ml/g. The results of gas sensitivity test show that the sample has the highest response and super good gas sensitivity selectivity. At 250∘C, the responses to 5[Formula: see text]ppm and 50[Formula: see text]ppm ethylene glycol can reach 14.4 and 293, respectively. Because of the excellent gas performance of ZnO nanosheets, this work can provide a theoretical basis for the research and development of ultra-sensitive ethylene glycol gas sensors in the industry.
From quantum electrodynamics to a geometric gauge theory of classical electromagnetism
Authors: Marsh Adam
Published: September 2023

A relativistic version of the correspondence principle, a limit in which classical electrodynamics may be derived from quantum electrodynamics (QED), has never been clear, especially when including gravitational mass. Here we introduce a novel classical field theory formulation of electromagnetism, and then show that it approximates QED in the limit of a quantum state which corresponds to a classical charged continua. Our formulation of electromagnetism features a Lagrangian which is gauge invariant, includes a classical complex field from which a divergenceless four-current may be derived, and reproduces all aspects of the classical theory of charged massive continua without any quantum effects. Taking a geometric approach, we identify the four-current as being in the direction of extremal phase velocity of the classical field; the field equations of motion determine this phase velocity as being equal to the mass, which makes the rest density proportional to the squared modulus of the field.
Petroleum generation and migration through the Faroe–Shetland Basin – the role of igneous intrusions
Authors: Mangione A. , Schofield N. , Holford S. , Grove C. , Ellis C. , Forster C. , Schenk O. , Gardiner D. , Hedley B. , Broadley L. , Underhill J. R.
Published: September 2023

Previous basin modelling of the Faroe–Shetland Basin (FSB, offshore UK) has suggested mid-Cretaceous petroleum generation, which predates the deposition of the working Paleogene reservoirs and traps. To justify the time discrepancy between generation, reservoir, and trap formation, factors such as intermediary accumulations and overpressure have been invoked. However, across much of the FSB, the Cretaceous sequences that overly the Kimmeridgian source rock are heavily intruded by Paleogene-aged intrusions. Recent modelling has shown that the emplacement of the intrusions, coupled with lower radiogenic heat production from underlying basement, leads to estimates of petroleum generation occurring up to 40 myr more recently than suggested by previous models. In this work, we seek to better understand the role that igneous intrusions have exerted on petroleum generation and migration in the FSB. Models with varying thicknesses of Paleogene intrusions are compared with those that consider the Cretaceous sequence as purely sedimentary (i.e. similar to assumptions in previous modelling). The estimated times of petroleum generation are compared with geochronological constraints on the ages of oils (i.e.
c
. 90–68 Ma) along with the deposition and formation of other petroleum system elements. By considering only the effect of igneous intrusions, the expulsion onset from the source rock is retarded by up to 12 myr. In addition, our models show the impact of the intrusions on petroleum saturation and migration, suggesting that intrusions have potentially compartmentalized the basin, trapping petroleum beneath or within the sill complex. Finally, our findings suggest that basin models in regions impacted by significant magmatism need to consider the impact of intrusions to more accurately constrain both petroleum generation and migration.

Thematic collection:
This article is part of the New learning from exploration and development in the UKCS Atlantic Margin collection available at:
https://www.lyellcollection.org/topic/collections/new-learning-from-exploration-and-development-in-the-ukcs-atlantic-margin
Al and H incorporation and Al-diffusion in natural rutile and its high-pressure polymorph TiO
2
(II)
Authors: Joachim-Mrosko Bastian , Konzett Jürgen , Ludwig Thomas , Griffiths Thomas , Habler Gerlinde , Libowitzky Eugen , Stalder Roland
Published: September 2023

Rutile is an important accessory mineral in metamorphic rocks and is used as a geothermobarometer or geochronometer. This study aims to bridge the gap between diffusion studies in simplified and complex natural systems by investigating the incorporation and mobility of Al in natural rutile and its high-pressure polymorph TiO
2
(II).

Experiments were performed at 0.1 MPa to 7 GPa, 1223–1373 K, at buffered μ(Al
2
O
3
) and with
f
O
2
constrained to ≤CCO, which is the equilibrium between graphite and a CO-CO
2
gas phase. Based on electron probe microanalysis, secondary ion mass spectrometry and Fourier transform infrared analyses, we suggest a complex combination of mechanisms to explain the incorporation of Al and H in natural rutile and TiO
2
(II). This includes: (1) the incorporation of Al
3+
on octahedral Ti-sites charge balanced by the formation of oxygen vacancies; and (2) the incorporation of oxygen in interstitial positions charge balanced by hydrogen interstitials.

Determined Al-diffusivities in natural TiO
2
are approximately eight to nine orders of magnitude faster compared to previously published data. A possible explanation includes a significantly enhanced rate of ionic diffusion through the combined effect of hydrolytic weakening, enhanced Al-diffusion through extended defects and to a minor extent oxygen fugacity variations. Consequently, results of this study question that the inferred high closure temperatures for the Al-in-rutile geothermobarometer can be applied to all natural systems.
Comparing the Expressiveness of the π-calculus and CCS
Authors: van Glabbeek Rob
Published: September 2023

This paper shows that the π-calculus with implicit matching is no more expressive than CCS
γ
, a variant of CCS in which the result of a synchronisation of two actions is itself an action subject to relabelling or restriction, rather than the silent action τ. This is done by exhibiting a compositional translation from the π-calculus with implicit matching to CCS
γ
that is valid up to strong barbed bisimilarity.

The full π-calculus can be similarly expressed in CCS
γ
enriched with the triggering operation of
Meije
.

I also show that these results cannot be recreated with CCS in the rôle of CCS
γ
, not even up to reduction equivalence, and not even for the asynchronous π-calculus without restriction or replication.

Finally, I observe that CCS cannot be encoded in the π-calculus.
Interplay Between Antimicrobial Resistance and Global Environmental Change
Authors: Zambrano María Mercedes
Published: September 2023

Antibiotic resistance genes predate the therapeutic uses of antibiotics. However, the current antimicrobial resistance crisis stems from our extensive use of antibiotics and the generation of environmental stressors that impose new selective pressure on microbes and drive the evolution of resistant pathogens that now threaten human health. Similar to climate change, this global threat results from human activities that change habitats and natural microbiomes, which in turn interact with human-associated ecosystems and lead to adverse impacts on human health. Human activities that alter our planet at global scales exacerbate the current resistance crisis and exemplify our central role in large-scale changes in which we are both protagonists and architects of our success but also casualties of unanticipated collateral outcomes. As cognizant participants in this ongoing planetary experiment, we are driven to understand and find strategies to curb the ongoing crises of resistance and climate change.