bluuebunny/crossref_metadata_2025 huggingface dataset:
Strong OLIG2 expression in supratentorial ependymoma, ZFTA fusion‐positive: A potential diagnostic pitfall
Authors: de Castro João Victor Alves , Kulikowski Leslie Domenicki , Wolff Beatriz Martins , Natalino Renato , Carraro Dirce Maria , Torrezan Giovana Tardin , Scapulatempo Neto Cristovam , Amancio Camila Trolez , Canedo Felipe Sales Nogueira Amorim , Feher Olavo , Costa Felipe D'Almeida
Published: October 2023

Ependymomas (EPN) are central nervous system neoplasms that exhibit an ependymal phenotype. In particular, supratentorial EPN (ST‐EPN) must be differentiated from more aggressive entities such as glioblastoma, IDH‐wildtype. This task is frequently addressed with the use of immunohistochemistry coupled with clinical presentation and morphological features. Here we describe the case of a young adult presenting with migraine‐like symptoms and a temporoinsular‐based expansile mass that was first diagnosed as a GBM, mostly based on strong and diffuse oligodendrocyte transcription factor 2 (OLIG2) expression. Molecular characterization revealed a ZFTA::RELA fusion, supporting the diagnosis of ST‐EPN, ZFTA fusion‐positive. OLIG2 expression is rarely reported in tumors other than GBM and oligodendrocyte‐lineage committed neoplasms. The patient was treated with radiotherapy and temozolomide after surgery and was alive and well at follow‐up. This report illustrates the need to assess immunostains within a broader clinical, morphological and molecular context to avoid premature exclusion of important differential diagnoses.
COBL7 is required for stomatal formation via regulation of cellulose deposition in Arabidopsis
Authors: Ge Shengchao , Sun Pengyue , Wu Wenjuan , Chen Xinhang , Wang Yifei , Zhang Min , Huang Jirong , Liang Yun‐Kuan
Published: October 2023

As a key regulator of plant photosynthesis, water use efficiency and immunity, stomata are specialized cellular structures that adopt defined shapes. However, our knowledge about the genetic players of stomatal pore formation and stomatal morphogenesis remains limited.

Forward genetic screening, positional cloning, confocal and electron microscopy, physiological and pharmacological assays were employed for isolation and characterization of mutants and genes.

We identified a mutant, dsm1, with impaired cytokinesis and deformed stomata. DSM1 is highly expressed in guard mother cells and guard cells, and encodes COBRA‐LIKE 7 (COBL7), a plant‐specific glycosylphosphatidylinositol (GPI)‐anchored protein. COBRA‐LIKE 7 and its closest homologue, COBL8, are first enriched on the forming cell plates during cytokinesis, and then their subcellular distribution and abundance change are correlated with the progressive stages of stomatal pore formation. Both COBL7 and COBL8 possess an ability to bind cellulose. Perturbing the expression of COBL7 and COBL8 leads to a decrease in cellulose content and inhibition of stomatal pore development. Moreover, we found that COBL7, COBL8 and CSLD5 have synergistic effects on stomatal development and plant growth.

Our findings reveal that COBL7 plays a predominant and functionally redundant role with COBL8 in stomatal formation through regulating cellulose deposition and ventral wall modification in Arabidopsis.
How plant traits respond to and affect vertebrate and invertebrate herbivores—Are measurements comparable across herbivore types?
Authors: Lebbink Gabrielle , Risch Anita C. , Schuetz Martin , Firn Jennifer
Published: October 2023

Despite plants realistically being affected by vertebrate and invertebrate herbivores simultaneously, fundamental differences in the ecology and evolution of these two herbivore guilds often means their impacts on plants are studied separately. A synthesis of the literature is needed to understand the types of plant traits examined and their response to, and effect on (in terms of forage selection) vertebrate and invertebrate herbivory, and to identify associated knowledge gaps. Focusing on grassland systems and species, we found 138 articles that met our criteria: 39 invertebrate, 97 vertebrate and 2 focussed on both vertebrate and invertebrate herbivores. Our study identified invertebrate focussed research, research conducted in the Southern Hemisphere and research on nondomesticated herbivores was significantly underrepresented based on our search and should be a focus of future research. Differences in study focus (trait response or trait effect), along with differences in the types of traits examined, led to limited opportunity for comparison between the two herbivore guilds. This review therefore predominantly discusses the response and effect of plant traits to each herbivore guild separately. In future studies, we suggest this review be used as a guide for trait selection, to improve comparability and the broader significance of results.
Incomplete resupination during floral development leads to pollination failure in a slipper orchid
Authors: Cardoso J. C. F. , Johnson S. D. , Oliveira P. E.
Published: October 2023

In many families, plants undergo floral resupination by twisting through approximately 180° during floral development so that the flower is effectively positioned upside down. In most orchids, resupination results in the median petal (i.e., the labellum) becoming lowermost, which plays a crucial role in pollination by serving as a landing platform or as a trapping device, or both. Incomplete resupination is predicted to lead to reduced pollination, although tests of this assumption are still lacking.

We investigated the effect of resupination using Phragmipedium vittatum, a rare lady's slipper orchid whose specialized labellum forms a trapping device. First, we surveyed the natural occurrence of incomplete resupination. Then we manipulated flowers into non‐ (≈0°), half‐ (≈90°), and fully resupinate (≈180°) positions to test the effect of orientation on pollen smear removal and deposition by pollinators (female hoverflies).

We found that ca. 10% of flowers in the natural population were not fully resupinate, being either non‐ (upward, 0–60°) or half‐resupinate (sideward, 60–120°). The change in orientation prevented the effectiveness of pollination by hoverflies since no pollen smear removal or deposition were found in flowers from non‐ and half‐resupinate treatments. Although these flowers still attracted hoverflies, they were not trapped effectively.

As this orchid is incapable of autonomous self‐pollination, flowers that do not resupinate fail to set fruits. These results highlight the importance of correct floral orientation provided by resupination to ensure pollination in orchids and other resupinate flowers.
Assessment of antibiotic use patterns in bovine mastitis treatment in the dairy sector in Serbia
Authors: Tomanić Dragana , Samardžija Marko , Kladar Nebojša , Pećin Marko , Ružić Zoran , Kovačević Zorana
Published: October 2023

The dairy sector is essential for the world's food systems, playing a vital role in agricultural production. Yet, mastitis, an inflammation of the mammary gland, affects a considerable portion of the dairy cow population annually, leading to reduced productivity and sustainability. Insight into therapeutic protocols is essential for a better understanding of the situation on farms with the aim of developing new or harmonizing existing protocols in the mastitis treatment. This study conducted on dairy farm in Serbia aimed to explore the most commonly used antibiotics during bovine mastitis treatment and their association with daily milk yield. Data from 100 lactating cows, including therapeutic protocols, lactation numbers, mastitis episodes, milk yield, and antibiotic usage, were obtained from a computerized database and statistically analysed. The results demonstrated a high prevalence of narrow‐spectrum antibiotics usage, with the majority of cows treated with combination therapy. The route of antibiotic application did not significantly impact daily milk yield, while treatment duration had no discernible effect. Nonetheless, specific antibiotics were associated with milk yield variations, suggesting the need for careful antibiotic selection and management in mastitis therapy. These findings emphasize the importance of prudent antibiotic use to safeguard animal health and long‐term milk production sustainability.
The novel HLA‐C allele, HLA‐C*01:02:84 allele, identified in a solid organ transplantation donor
Authors: Yang Jin Hyuk , Yang John Jeongseok , Oh Heung‐Bum
Published: October 2023

HLA‐C*01:02:84 differs from HLA‐C*01:02:01:01 by one synonymous nucleotide substitution in codon 48.
Characterization of the novel HLA‐DRB1*10:38 allele, showing an extended cytoplasmic tail
Authors: Balas Antonio , Sanchez‐Gordo Francisco , Moreno‐Hidalgo Miguel‐Ángel , García‐Sánchez Félix , Vicario José L.
Published: October 2023

Sequence and expression analysis of the HLA‐DRB1*10:38 allele.
Two-dimensional and Three-dimensional Image-guided Evaluation of Patient Positioning for Intensity-modulated Radiation Therapy of Head and Neck Cancer
Authors: Johari Zul Iskandar , Azmi Nor Aniza , Ab Muin Nur Fa’izah , A Latiff Rukiah , Ahmad Fadzil Muhammad Safwan , Ahmad Razali Rosmizan
Published: October 2023

Patient positioning accuracy is critical in radiation therapy, especially in intensity-modulated radiation therapy (IMRT) for head and neck cancer (HNC), as it can affect treatment effectiveness and safety. This retrospective study aimed to evaluate the accuracy of patient positioning techniques and compare the effectiveness of using multiple image-guided (IG) methods for IG-IMRT of HNC. Cone-beam computed tomography (CBCT) and kV-planar imaging (OBI) collected 3240 treatment couch coordinates in three translational directions from 60 HNC patients undergoing IMRT. Inter-fraction errors were assessed by registering the scans to the planning CT, and the population systematic set-up error (Σ), random error (σ), and planning target volume (PTV) margin were calculated. The results between OBI and CBCT were analyzed and compared using one-way ANOVA. The findings demonstrated that more than 80% of the image-guided patient positioning set-ups were acceptable. The mean couch displacement for image-guided techniques was negligible in all translational directions using OBI and CBCT. However, the PTV margin for both methods was more than 0.5 cm, except for the CBCTA-P direction. This study highlights the effectiveness of OBI and CBCT as modalities for evaluating and improving the accuracy of IMRT in HNC patients. Determination of the systematic and random errors and calculating the optimal PTV margin without rematching images can help improve the precision of patient positioning and ultimately lead to better treatment outcomes.
Numerical Modeling of Swirl Stabilized Lean-Premixed H2–CH4 Flames With the Artificially Thickened Flame Model
Authors: Castellani S. , Nassini P. C. , Andreini A. , Meloni R. , Pucci E. , Valera-Medina A. , Morris S. , Goktepe B. , Mashruk S.
Published: October 2023

The lean premixed technology is a very convenient combustion strategy to progressively move from natural gas to high hydrogen content fuels in gas turbines limiting the pollutants emissions at the same time. The enabling process that will allow the combustor to manage a full H2 operation requires relevant design modifications, and in this framework, the numerical modeling will be a pivotal tool that will support this transition. In this work, high-fidelity simulations of perfectly premixed swirl stabilized flames have been performed varying the H2 content in the fuel from 0 to 100% to investigate the effect of the hydrogen addition on the methane flame. The artificially thickened flame model (ATFM) has been used to treat the turbulent chemistry interaction. The numerical results have been compared with the detailed experimental data performed at Cardiff University's Gas Turbine Research Center. After the numerical model validation against experimental OH* chemiluminescence maps has been presented, a deep numerical investigation of the effect of the H2 addition on the flame has been performed. In this way, the work aims to highlight the good prediction capability of the ATFM, and, at the same time, highlight the change in the different contributions that govern the flame reactivity moving from 100% CH4 to 100% H2 in very lean conditions.
U.S. hands out $7 billion for hydrogen hubs
Authors: Bourzac Katherine
Published: October 2023

Gas could replace fossil fuels and fight climate change—if it is made cleanly
The sensor histidine kinase (SLN1) and acetyl-CoA carboxylase (ACC1) coordinately regulate the response of
Neurospora crassa
to the springtail
Sinella curviseta
(Collembola: Entomobryidae) attack
Authors: Sun Mengni , Lu Ting , Chen Pengxu , Wang Xiaomeng , Yang Hanbing , Zhou Rong , Zheng Weifa , Zhao Yanxia
Published: October 2023

Eukaryotes evolved various strategies to coordinate their development and metabolism in response to harsh environments. However, it remains unknown whether fungi increase their resistance to stress from fungivorous arthropods by altering phenotype and metabolite composition. In this study, we investigated the coordinated regulation of sensor histidine kinase (SLN1) and acetyl-CoA carboxylase (ACC1) on sporulation and metabolite accumulation in
Neurospora crassa
, particularly upon the springtail
Sinella curviseta
(Collembola: Entomobryidae) attack. The mutants
Δsln1
,
Δacc1
, and double mutant
Δsln1::Δacc1
exhibited reduced conidia number and defective sexual reproduction in contrast to the wild type. Intriguingly, double deletion of
sln1
and
acc1
results in failure of beak formation and, consequently, inhibits ascospores ejection which helps
Δsln1::Δacc1
to escape the predation by
S. curviseta
. Furthermore,
sln1
and/or
acc1
play critical roles in metabolic processes in
N. crassa
. Compared with the control, the cultures exposed to
S. curviseta
produced more trehalose, carotenoids, folic acid, and fatty acids, especially in the asexual stage. The deletion of
sln1
and
acc1
affected the trehalose content, thereby reducing the resistance of
Δsln1
,
Δacc1
, and
Δsln1::Δacc1
to
S. curviseta
. Null of
sln1
and/or
acc1
altered the lipid composition and thus carotenoids synthesis. Chemical analysis showed that
N. crassa
formed more fatty acids and carotenoids upon the attack of
S. curviseta
. Taken together, our data suggest that
acc1
and
sln1
work together to protect
N. crassa
from the stress of
S. curviseta
. SLN1 and ACC1 compose a regulatory system that coordinates the conidiation, perithecial formation, and metabolism, especially upon fungivores stress.

IMPORTANCE

Understanding the regulatory pathways by which fungi respond to environmental signals through interlinked genes provides insights into the interactions between fungi and insects. The coordinated optimization of the regulatory networks is necessary for fungi to adapt to their habitats. We demonstrated that the synergistic regulation of sensor histidine kinase (SLN1) and acetyl-CoA carboxylase (ACC1) plays a critical role in regulating the fungal response to
Sinella curviseta
stress. Furthermore, we found that the enhanced production of trehalose, carotenoids, and 5-MTHF plays crucial role in the resistance to the fungivore. Our results provide insights into the understanding of the adaptation of
N. crassa
to environmental stimuli.
Closed circular genome sequence of a
Microcystis aeruginosa
PCC7806 Δ
mcyB
(UTK) non-toxic mutant
Authors: Stark Gwendolyn F. , Truchon Alexander R. , Dittmann Elke , Wilhelm Steven W.
Published: October 2023

Here we report the complete, closed genome of the non-toxic
Microcystis aeruginosa
PCC7806 Δ
mcyB
mutant strain. This genome is 5,103,923 bp long, with a GC content of 42.07%. Compared to the published wild-type genome (
Microcystis aeruginosa
PCC7806SL), there is evidence of accumulated mutations beyond the inserted chloramphenicol resistance marker.
Draft genome sequences of six bacteria isolated from polylactic acid samples from the Mediterranean Sea
Authors: Rojas-Vargas Jorge , Adaya Libertad , Lacerda Ana Luzia , Pedrotti Maria-Luiza , Sanchez-Flores Alejandro , Pardo-López Liliana
Published: October 2023

Here, we report the draft genome sequences of six marine strains isolated from plastic samples incubated in the Mediterranean Sea. Genomic analyses place these strains within the
Alkalihalobacillus
,
Bacillus
,
Halomonas
, and
Marinobacter
genera. Examining the genomes of these non-typical environmental bacteria increases our comprehension of microorganism biology and their potential uses.
Insight into the invasion process and immune-protective evaluation of Tp0971, a membrane lipoprotein from
Treponema pallidum
Authors: Zhang Xiaohong , Duan Junxia , Wang Yali , Xie Bibo , Zhou Jie , Zhao Sisi , Yin Weiguo , Liu Peng , Zhao Feijun
Published: October 2023

Treponema pallidum
(
T. pallidum
), the pathogen of syphilis, can invade organisms through mucous membranes or broken skin and proliferate in the host. It spreads rapidly and causes chronic systemic multi-organ damage. Currently, the invasion and pathogenesis of
T. pallidum
remain a mystery. In this study, we established a
T. pallidum
infection model in New Zealand rabbits, and the
T. pallidum
burden in various tissues and organs was detected to investigate the dynamic spread of
T. pallidum
in different organs. Our results indicated that the
T. pallidum
burden in rabbits was in a cyclic and repeated dynamic process of decreasing and increasing after infection. In addition, the localization of lipoprotein Tp0971 was confirmed by using the gel microdroplet method. We found that Tp0971 might be a membrane lipoprotein that exists in the inner and outer membranes of
T. pallidum
. The immune-protective effect of the
T. pallidum
infection-dependent antigen Tp0971 was evaluated. Tp0971/CpG can induce high levels of Tp0971-specific antibodies, delay skin damage, and promote healing at the infected sites of
T. pallidum
in New Zealand rabbits. This indicated that Tp0971 may serve as a vaccine antigen candidate. Our results provide new ideas for future research on the proliferation, spread mechanism, and vaccine development of
T. pallidum
.

IMPORTANCE

The past two decades have seen a worldwide resurgence in infections caused by
Treponema pallidum
(
T. pallidum
) subsp.
pallidum
, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation “the stealth pathogen.” There are many hurdles to studying syphilis pathogenesis, most notably the difficulty of culturing and genetically manipulating
T. pallidum
, as well as the absence of an effective vaccine for
T. pallidum
prevention.
T. pallidum
infection in humans is a complex and lengthy process. In this study, we investigated the invasion process and the function of the infection-dependent antigen Tp0971 as an immunogen to inhibit the dissemination of
T. pallidum
in an animal infection model. This enables a better understanding of the specific pathogenic mechanism of this pathogen, syphilis pathogenesis, and vaccine research.
Prevalence and virulence potential of
Aeromonas
spp. isolated from human diarrheal samples in North East Italy
Authors: Bernabè Giulia , Brun Paola , Pietra Giuseppe Di , Zatta Veronica , Asad Shirin , Meneghello Silvia , Cordioli Giampaolo , Lavezzo Enrico , Valente Elisabetta , Mietto Sofia , Besutti Valeria , Castagliuolo Ignazio
Published: October 2023

Aeromonas
spp. are emerging human pathogens causing intestinal and extra-intestinal infections. Since their relevance in Western Europe as gastrointestinal pathogens is not well established, we investigated
Aeromonas
spp. prevalence in diarrheal fecal samples in an Italian University Hospital and characterized the virulence mechanisms of the isolates.
Aeromonas
spp. isolated from diarrheic stools using standard culture methods were identified by molecular techniques. Antimicrobial resistance was assessed by the micro broth dilution. Toxins, flagella, and type III secretion system genes were evaluated by polymerase chain reaction. Biofilm was quantified by crystal-violet staining. Interaction with human intestinal epithelial cells (Caco-2) was assessed by quantifying adhesion, interleukin (IL)-8 secretion, and epithelial barrier integrity.
Aeromonas
spp. represented 20.6% of bacterial pathogens isolated from diarrheic feces, the second most common enteropathogen.
A. cavieae
constituted 75% of the identified species, showing a relatively low clustering value. About 52% of
Aeromonas
isolates showed resistance to amikacin, whereas only 7.5% showed multiple drug resistance. Four or more virulence genes were identified in 66.7% of
A. cavieae
isolates and 100% of
A. dakensis. Aeromonas
isolates (82.5%) showed moderate or important biofilm-producing ability. Adhesion to Caco-2 cells correlated to
fla
+ gene, whereas
ascV+
and
aexU
+ strains significantly induced IL-8 release from Caco-2.
Aeromonas aer+
strains caused ZO1 and occluding redistribution and a significative reduction in trans-epithelial resistance.
Aeromonas
spp. emerge as relevant human intestinal pathogens with a disparate arsenal of pathogenicity factors causing diarrhea through different mechanisms.

IMPORTANCE

In this work, we demonstrate the epidemiologic relevance of the
Aeromonas
genus as the cause of infective diarrhea in North East Italy, both in children and adult subjects, with the significative presence of highly pathogenic strains.
Aeromonas
strains possess a heterogeneous armamentarium of pathogenicity factors that allows the microbe to affect a wide range of human intestinal epithelial cell processes that justify the ability to induce diarrhea through different mechanisms and cause diseases of variable severity, as observed for other gastrointestinal pathogens. However, it remains to be determined whether specific genotype(s) are associated with clinical pictures of different severity to implement the diagnostic and therapeutic approaches for this relevant enteric pathogen.
Antiviral, antioxidant, and anti-inflammatory activities of rhein against white spot syndrome virus infection in red swamp crayfish (
Procambarus clarkii
)
Authors: Chen Cheng , Liang Chang-Shuai , Wang Tao , Shen Jing-Lei , Ling Fei , Jiang Hai-Feng , Li Peng-Fei , Wang Gao-Xue
Published: October 2023

Infection caused by white spot syndrome virus (WSSV) leads to massive mortality and huge economic losses in the crustacean aquaculture industry; however, to date, no effective control means are available to control the disease. Thus, to better understand the pathological aspects of WSSV and to find effective compounds that have the potential to be developed as anti-WSSV agents are imperative. Herein, based on screening of plants with antiviral activity, we found that rhein, an anthraquinone compound in
Rheum palmatum
L., exhibited strong activity against WSSV infection in a red swamp crayfish (
Procambarus clarkii
) model. The results showed that rhein could dose dependently inhibit transcription of WSSV ie1, DNApol, and Vp28 genes, reduce viral load
in vivo
, and significantly improve the survival rate of WSSV-infected crayfish. Through investigation of the mechanisms of action, we found that rhein did not affect the infectivity of viral particles
in vitro
as well as the entry and release process
in vivo
. Alternatively, rhein could activate JAK/STAT and NF-κB pathways, significantly decrease the expression of crustin-1 and BAF but increase the expression of C-type lectin and proPO to arrest WSSV replication. Moreover, rhein also attenuated WSSV-induced oxidative and inflammatory stresses by regulating the expression of antioxidant and anti-inflammatory-related genes and enhanced innate immunity by reducing total protein levels while increasing the phosphatase activity. Taken together, our study shows rhein as a potent WSSV inhibitor, which provides great potential for the development of prophylaxis and therapy agents for controlling WSSV infection in crustacean aquaculture.

IMPORTANCE

Aquaculture is essential for ensuring global food security by providing a significant source of animal protein. However, the spread of the white spot syndrome virus (WSSV) has resulted in considerable economic losses in crustacean industries. In this study, we evaluated the antiviral activity of rhein, the primary bioactive component of
Rheum palmatum
L., against WSSV infection, and many pathological aspects of WSSV were also described for the first time. Our mechanistic studies indicated that rhein effectively arrested the replication of WSSV in crayfish by modulating innate immunity to inhibit viral gene transcription. Furthermore, we observed that rhein attenuated WSSV-induced oxidative and inflammatory stresses by regulating the expression of antioxidant and anti-inflammatory-related genes while enhancing innate immunity by reducing total protein levels and increasing phosphatase activity. Our findings suggest that rhein holds great promise as a potent antiviral agent for the prevention and treatment of WSSV in aquaculture.
Genetic and phenotypic characterizations of IncX3 plasmids harboring
bla
NDM-5
and
bla
NDM-16b
in Japan
Authors: Zuo Hui , Sugawara Yo , Kayama Shizuo , Kawakami Sayoko , Yahara Koji , Sugai Motoyuki
Published: October 2023

The spread of the gene encoding the NDM-type carbapenemase,
bla
NDM
, poses a serious threat to clinical practice and public health. This gene is usually carried by transferable plasmids, which facilitates its rapid spread among various species of Enterobacterales. Plasmids with the IncX3 replicon play a major role in the spread of
bla
NDM
in Asian countries. In this study, we conducted genomic sequencing and a comparative analysis of the IncX3-type plasmids harboring
bla
NDM-5
and
bla
NDM-16b
, a single-nucleotide variant of
bla
NDM-5
, isolated in a national antimicrobial-resistant bacterial genomic surveillance in Japan (Japan Antimicrobial Resistant Bacterial Surveillance), which was carried out during 2019–2020. We compared five plasmids harboring
bla
NDM-5
and one plasmid harboring
bla
NDM-16b
. They were highly identical and differed in several nucleotide substitutions or variations in insertion sequences, although they were carried by different species or genotypes. Notably,
bla
NDM-16b
-carrying pJBBDACG-19-0070 was identical to a plasmid carrying
bla
NDM-5
except for one nucleotide substitution in the
bla
NDM
gene throughout the 46 kb sequences. Transformants carrying these two plasmids showed comparative resistance to carbapenems, indicating that a substitution on the NDM enzyme (Ala233 to Val) did not affect carbapenem resistance, at least under normal experimental conditions. A database search revealed that several identical plasmids carrying
bla
NDM-5
were reported from neighboring countries, mainly China, before our surveillance period. Our analysis suggested that the IncX3 plasmid harboring
bla
NDM-5
is spreading in Japan, and
bla
NDM-16b
emerged from a single nucleotide substitution on the plasmid, with widespread dissemination in Asian countries.

IMPORTANCE

IncX3 plasmids harboring
bla
NDM-5
play a major role in the spread of carbapenem resistance in Asia, particularly in China, in clinical and environmental settings. In this study, we present that Enterobacterales isolates carrying IncX3 plasmids harboring
bla
NDM-5
have been disseminated in Japan, where their identification was previously rare. In addition,
bla
NDM-16b
, a single-nucleotide variant of
bla
NDM-5
, was found to be carried by an identical IncX3 plasmid. A comparative sequence analysis revealed that the
bla
NDM-16b
gene emerged from a single nucleotide substitution on an IncX3 plasmid harboring
bla
NDM-5
. The
bla
NDM-16b
gene did not confer elevated carbapenem resistance compared to
bla
NDM-5
in our assay using transformants carrying the plasmid harboring either of these genes, although the A233V substitution was reported to confer stability to the enzyme in ion-depleted conditions. Nevertheless, vigilance regarding the emergence of novel variants is required.
TCA cycle tailoring facilitates optimal growth of proton-pumping NADH dehydrogenase-dependent
Escherichia coli
Authors: Goel Nikita , Srivastav Stuti , Patel Arjun , Shirsath Akshay , Panda Tushar Ranjan , Patra Malay , Feist Adam M. , Anand Amitesh
Published: October 2023

The bacterial lifestyle is plastic, requiring transcriptional, translational, and metabolic tailoring for survival. These dynamic cellular processes are energy intensive; therefore, flexible energetics is requisite for adaptive plasticity. An intricate network of complementary and supplementary pathways exists in bacterial energy metabolism. There are two main entry points for electrons in the aerobic electron transport system, NADH dehydrogenase (NDH) and succinate dehydrogenase (SDH), receiving electrons from NADH and succinate, respectively. Aerobic bacterial phyla have a non-proton-pumping NADH dehydrogenase, which is often the primary dehydrogenase under aerobiosis. Here, we report adaptive changes supporting growth restoration in an
Escherichia coli
strain lacking the primary dehydrogenase. Growth optimization is achieved by reducing the activity of succinate dehydrogenase, and thus we demonstrate a physiological discord between proton-pumping NADH dehydrogenase and succinate dehydrogenase in supporting growth. Beyond the fundamental understanding of the bioenergetic network, identifying this compensatory feature provides impetus to rational antimicrobial combinations for targeting the non-proton-pumping dehydrogenase.

IMPORTANCE

Energy generation pathways are a potential avenue for the development of novel antibiotics. However, bacteria possess remarkable resilience due to the compensatory pathways, which presents a challenge in this direction. NADH, the primary reducing equivalent, can transfer electrons to two distinct types of NADH dehydrogenases. Type I NADH dehydrogenase is an enzyme complex comprising multiple subunits and can generate proton motive force (PMF). Type II NADH dehydrogenase does not pump protons but plays a crucial role in maintaining the turnover of NAD+. To study the adaptive rewiring of energy metabolism, we evolved an
Escherichia coli
mutant lacking type II NADH dehydrogenase. We discovered that by modifying the flux through the tricarboxylic acid (TCA) cycle,
E. coli
could mitigate the growth impairment observed in the absence of type II NADH dehydrogenase. This research provides valuable insights into the intricate mechanisms employed by bacteria to compensate for disruptions in energy metabolism.
Anaphylatoxin signaling activates macrophages to control intracellular
Rickettsia
proliferation
Authors: Dahmani Mustapha , Zhu Jinyi C. , Cook Jack H. , Riley Sean P.
Published: October 2023

Pathogenic
Rickettsia
species proliferate within the cytoplasm of permissive host cells
in vivo
. The cytoplasm of these host cells is adequate to support the complex metabolic and physiological needs for
Rickettsia
growth. However, a dramatic host/pathogen interplay occurs when
Rickettsia
encounter innate immune cells, whereby the bacteria can proliferate as normal or the host can restrict bacterial growth. This interplay is most divergent within myeloid host cells, where intra- and extracellular factors can produce either successful
Rickettsia
parasitism or innate immune control of bacterial proliferation. With the prior knowledge that the mammalian complement system is activated during mammalian infection, we sought to determine if extracellular complement activation and anaphylatoxin signaling can modify the fate of
Rickettsia
within mononuclear host cells. Results indicate that supplementation of growth media with either C3a or C5a anaphylatoxin peptides is sufficient for many myeloid cells to control the proliferation of multiple different
Rickettsia
species. Chemical or genetic disruption of anaphylatoxin signaling or anaphylatoxin receptors eliminates complement-induced restriction of bacterial proliferation. Finally, anaphylatoxin signaling modifies macrophage physiology by inducing inflammatory phenotypes that ultimately control the intracellular proliferation of these pathogens.

IMPORTANCE

Pathogenic
Rickettsia
species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when
Rickettsia
encounter innate immune cells; the bacteria can “win” by taking over the host, or the bacteria can “lose” if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of
Rickettsia
and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that “activate” innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.
Choroidal thickness in patients with thyroid-associated ophthalmopathy, as determined by swept-source optical coherence tomography
Authors: Zhong Sisi , He Fanglin , Fang Sijie , Sun Jing , Li Yinwei , Shuo Zhang , Liu Xingtong , Song Xuefei , Wang Yang , Huang Yazhuo , Zhou Huifang , Fan Xianqun
Published: October 2023

Aim

This study used swept-source optical coherence tomography (SS-OCT) to investigate subfoveal choroidal thickness (SFCT) in patients with thyroid-associated ophthalmopathy (TAO) who displayed different levels of disease activity and severity.

Methods

Thirty patients with TAO (60 eyes) and 38 healthy controls (67 eyes) in Shanghai, China, were recruited for this study. Disease activity and severity were graded using European Group on Graves’ Orbitopathy standardised criteria. SFCT values were determined by SS-OCT.

Results

In total, 129 eyes were included in the final analysis. The mean SFCT was significantly thicker among patients with active disease (276.23±84.01 µm) than among patients with inactive disease (224.68±111.61 µm; p=0.049) or healthy controls (223.56±78.69 µm; p=0.01). There were no differences in SFCT among patients with moderate-to-severe disease, patients with severe disease and healthy controls (p>0.05). Changes in SFCT demonstrated strong predictive ability to distinguish active TAO from inactive TAO (area under the curve=0.659, 95% CI 0.496 to 0.822).

Conclusions

SFCT was strongly associated with Clinical Activity Score in patients with TAO. Choroidal thickening was observed during active TAO. SS-OCT offers a non-invasive method for follow-up assessment.
Developing a privacy-preserving deep learning model for glaucoma detection: a multicentre study with federated learning
Authors: Ran An Ran , Wang Xi , Chan Poemen P , Wong Mandy O M , Yuen Hunter , Lam Nai Man , Chan Noel C Y , Yip Wilson W K , Young Alvin L , Yung Hon-Wah , Chang Robert T , Mannil Suria S , Tham Yih-Chung , Cheng Ching-Yu , Wong Tien Yin , Pang Chi Pui , Heng Pheng-Ann , Tham Clement C , Cheung Carol Y
Published: October 2023

Background

Deep learning (DL) is promising to detect glaucoma. However, patients’ privacy and data security are major concerns when pooling all data for model development. We developed a privacy-preserving DL model using the federated learning (FL) paradigm to detect glaucoma from optical coherence tomography (OCT) images.

Methods

This is a multicentre study. The FL paradigm consisted of a ‘central server’ and seven eye centres in Hong Kong, the USA and Singapore. Each centre first trained a model locally with its own OCT optic disc volumetric dataset and then uploaded its model parameters to the central server. The central server used FedProx algorithm to aggregate all centres’ model parameters. Subsequently, the aggregated parameters are redistributed to each centre for its local model optimisation. We experimented with three three-dimensional (3D) networks to evaluate the stabilities of the FL paradigm. Lastly, we tested the FL model on two prospectively collected unseen datasets.

Results

We used 9326 volumetric OCT scans from 2785 subjects. The FL model performed consistently well with different networks in 7 centres (accuracies 78.3%–98.5%, 75.9%–97.0%, and 78.3%–97.5%, respectively) and stably in the 2 unseen datasets (accuracies 84.8%-87.7%, 81.3%-84.8%, and 86.0%–87.8%, respectively). The FL model achieved non-inferior performance in classifying glaucoma compared with the traditional model and significantly outperformed the individual models.

Conclusion

The 3D FL model could leverage all the datasets and achieve generalisable performance, without data exchange across centres. This study demonstrated an OCT-based FL paradigm for glaucoma identification with ensured patient privacy and data security, charting another course toward the real-world transition of artificial intelligence in ophthalmology.
Depression and anxiety-related disorders and suicide among Swedish male elite football players: a nationwide cohort study
Authors: Kader Manzur , Pasternak Björn , Lim Carl-Emil , Neovius Martin , Forssblad Magnus , Svanström Henrik , Ludvigsson Jonas F , Ueda Peter
Published: October 2023

Objective

To assess whether male elite football players, during and after their active career, were at increased risk of depression and anxiety-related disorders and suicide, as compared with the general male population.

Methods

We included male football players active in the Swedish top division 1924–2019 and general male population (matched to football players based on age and region of residence) aged <65 years in 1997. Using nationwide registers, we followed the football players from their first season in the top division (or the date of their first registered residency in Sweden) or 1 January 1997, and compared the risk of depression and anxiety-related disorders (captured through diagnoses from hospital admissions and outpatient visits, and use of prescription drugs) among football players versus controls. In a secondary analysis using data from death certificates, we compared the risk of suicide between football players and general population males who were alive in 1969 (when cause of death became available) .

Results

During follow-up through 31 December 2020, 504 (13.6%) of 3719 football players and 7455 (22.3%) of 33 425 general population males had a depression or anxiety-related disorder. In analyses accounting for age, region of residence and calendar time, the risk of anxiety and depression-related disorders was lower among football players versus general population males (HR 0.61, 95% CI 0.55 to 0.66). The protective association was attenuated with increasing age, and from around age 70 years the risk was similar in the two groups. The risk of suicide was lower among football players versus general population males (HR 0.48, 95% CI 0.32 to 0.72).

Conclusions

In this nationwide cohort study in Sweden, elite male football players had a lower risk of depression and anxiety-related disorders and suicide as compared with the general population.
Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial
Authors: Lee Yong-Joon , Hong Sung-Jin , Kang Woong Chol , Hong Bum-Kee , Lee Jong-Young , Lee Jin-Bae , Cho Hyung-Jin , Yoon Junghan , Lee Seung-Jun , Ahn Chul-Min , Kim Jung-Sun , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Jang Yangsoo , Hong Myeong-Ki
Published: October 2023

Objective

To compare the long term efficacy and safety of rosuvastatin with atorvastatin treatment in adults with coronary artery disease.

Design

Randomised, open label, multicentre trial.

Setting

12 hospitals in South Korea, September 2016 to November 2019.

Participants

4400 adults (age ≥19 years) with coronary artery disease.

Interventions

Participants were assigned to receive either rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomisation.

Main outcome measures

The primary outcome was a three year composite of all cause death, myocardial infarction, stroke, or any coronary revascularisation. Secondary outcomes were safety endpoints: new onset diabetes mellitus; hospital admissions due to heart failure; deep vein thrombosis or pulmonary thromboembolism; endovascular revascularisation for peripheral artery disease; aortic intervention or surgery; end stage kidney disease; discontinuation of study drugs owing to intolerance; cataract surgery; and a composite of laboratory detected abnormalities.

Results

4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2%
v
5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5%
v
1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups.

Conclusions

In adults with coronary artery disease, rosuvastatin and atorvastatin showed comparable efficacy for the composite outcome of all cause death, myocardial infarction, stroke, or any coronary revascularisation at three years. Rosuvastatin was associated with lower LDL cholesterol levels but a higher risk of new onset diabetes mellitus requiring antidiabetics and cataract surgery compared with atorvastatin.

Trial registration

ClinicalTrials.gov
NCT02579499
.
Exposure to low-dose radiation in occupational settings and ischaemic heart disease: a systematic review and meta-analysis
Authors: Peters Cheryl E , Quinn Emma Kathleen , Rodriguez-Villamizar Laura Andrea , MacDonald Heather , Villeneuve Paul J
Published: October 2023

Ionising radiation is a human carcinogen, but the evidence is less clear that exposure to low-dose ionising radiation (LDIR) increases the risk of adverse cardiovascular outcomes. We synthesised the literature of chronic occupational exposure to LDIR and cardiovascular disease, particularly for ischaemic heart disease (IHD).

The literature search was conducted using three databases including studies published between 1990 and 2022. A quality assessment of the studies was completed using the Office of Health and Assessment and Translation Risk of Bias Rating Tool. We conducted meta-analyses for IHD mortality using random effects models using measures of excess relative risk per sievert (ERR/Sv) obtained from internal cohort comparisons, as well as with standardised mortality ratios (SMRs) from external cohort comparisons.

We identified 2189 articles, and of these, 26 provided data on IHD and were retained. Most studies were classified as having a ‘moderate’ level of risk of bias. Fourteen and 10 studies reporting external radiation doses were included in meta-analyses using SMR and ERR/Sv, respectively. The meta-summary SMR was 0.81 (95% CI 0.74 to 0.89) with evidence of reduced risk but high heterogeneity across studies. For internal cohort measures, the summary ERR/Sv for a lagged exposure of 10 years was 0.10 (95% CI 0.01 to 0.20) with low heterogeneity. The subgroup analysis by lagged exposure time showed the strongest association were for the 15 and 20 years lag.

Our findings suggest that occupational exposure to LDIR increases the risk IHD mortality and highlight the relevance of internal cohort comparisons.
Associations of cow-level factors with the risk of poor hygiene in cows housed in free-stall and tie-stall barns
Authors: Robles I. , Kelton D.F. , DeVries T.J.
Published: October 2023

The objective of this study was to identify cow-level factors associated with poor body hygiene. Cows ( n = 2644) from 68 commercial dairy herds (free-stall ( n = 43); tie-stall ( n = 25)) in Ontario, Canada were enrolled. Cows were hygiene scored on each of three visits (7 days apart). Older cows were at higher risk of having a dirty udder and dirty upper legs and flanks in free-stall barns and younger cows were at higher risk of having dirty upper legs and flanks in tie-stall barns. Higher days in milk was associated with better hygiene for cows housed in both free-stall and tie-stall barns.
Stability of power law cosmological model in f(Q) gravity
Authors: Garg Priyanka , Bhardwaj Vinod Kumar
Published: October 2023

In the present study, we have described the accelerated cosmological models of the universe in f( Q) gravity. In f( Q) gravity, the gravitational field equations are modified by a function of the non-metricity tensor, which characterizes the deviation of the affine connection from the metric compatibility condition. We have considered two different forms of f( Q) gravity as f( Q) = β + α  Q( n + 1) and f( Q) = β  Q + α  Q n to explain the dynamics of the expanding universe. We have discussed the dynamics of the universe through graphical representation by considering the power law ( a = kt m ). The free parameters of the models are fitted with the latest observational data set of observational Hubble data, consisting of 57 points, using statistical analysis based on the Markov Chain Monte Carlo method. The best-fit values for the model’s parameter are estimated as H0 = 67.3 ± 1.1, m = 1.0213 ± 0.0071, and k = 65.4 ± 1.1. The parameters of the derived model, like energy density, isotropic pressure, EoS (Equation of state) parameter, and jerk parameter, are discussed. We have described the energy conditions to explain the viability of the considered models. We have also verified the stability of the derived model through perturbation analysis.
Moult migrant Tennessee Warblers undergo extensive stopover in peri-urban forests of southern Quebec
Authors: Poirier Vanessa , Frei Barbara , Lefvert Mathilde , Morales Ana , Elliott Kyle H.
Published: October 2023

Stopovers are the most energy- and time-consuming events during avian migration, yet individuals of certain species make long stopovers to moult (“moult migration”). Requiring abundant energy and a prolonged stay, moult migrants should occupy small stopover home ranges in resource-rich habitats. Understanding migrant behaviour at their stopovers is critical for implementing conservation efforts for declining Neotropical passerines. To examine the stopover timing and habitat use of one such moult migrating passerine, we radio-tagged 18 moulting and 4 post-moult Tennessee Warblers ( Leiothlypis peregrina (A. Wilson, 1811)) at an autumn stopover site. Although our data were biased towards one sampling year, moult migrants generally arrived at the stopover site earlier (average = 2 August) than post-moult migrants (average = 12 September). Moult migrants also stayed longer (46 ± 5 days) than post-moult migrants (8 ± 6 days) and had large overlapping stopover home ranges (∼15 ha) that were dependent on high abundance of forest (%) and forest edge (m). We conclude that Tennessee Warblers occupied forested stopover sites within a peri-urban landscape where they successfully moulted before continuing migration. This study illustrates the importance of including stopover sites in conservation plans, particularly in cities where quality habitats are scarce.