bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy evaluation of a bivalent subunit vaccine against epidemic PEDV heterologous strains with low cross-protection
Authors: Song Xu , Li Yunchuan , Wang Chuanhong , Zhao Yongxiang , Yang Shanshan , Guo Rongli , Hu Mi , Sun Min , Zhang Gege , Li Yupeng , Wang Yi , Liu Shiyu , Shen Yaoxin , Li Chengcheng , Zhang Xuehan , Li Jizong , Fan Baochao , Li Bin
Published: September 2024

Variant
Porcine epidemic diarrhea virus
(PEDV), which causes diarrhea and high mortality in piglets, has become a major pathogen, and co-epidemics of different subtypes of the virus have become a very thorny problem for the clinical prevention and control of PEDV. However, cross-protection between epidemic G2a and G2b subtype strains has not been observed, and there is currently no vaccine against both G2a and G2b strains. In this study, we demonstrate the low cross-protection between G2a and G2b strains with piglet immunization and challenge tests. The trimeric full-length S proteins of G2a and G2b variants were purified and a bivalent subunit vaccine against PEDV G2a/G2b-S was developed. In active and passive immune protection tests, the bivalent subunit vaccine produced high neutralizing antibody titers and S-specific immunoglobulin G (IgG) and IgA titers against both the G2a and G2b strains in piglets and sows. In the attack phase of the viruses, the clinical symptoms and microscopic lesions in the immunized groups were significantly alleviated. Importantly, the PEDV G2a/G2b-S bivalent subunit vaccine conferred effective passive immunity against PEDV G2a and G2b challenges in the form of colostrum-derived antibodies from the immunized sows. In conclusion, our data demonstrate the low cross-protection of PEDV epidemic G2a and G2b strains and show that the G2a/G2b-S bivalent subunit vaccine is protective against both G2a and G2b strains. It is therefore a candidate vaccine for PEDV prevention.

IMPORTANCE

The detection rate of PEDV G2a subtype strains is currently increasing. Although commercial vaccines are available, most vaccines do not exert an ideal protective effect against these strains. Furthermore, there is no definitive research into the cross-protection between G2a and G2b strains, and no bivalent vaccine provides joint protection against both. Therefore, in this study, we investigated the cross-protection between PEDV G2a and G2b strains and designed a candidate bivalent subunit vaccine combining the trimeric S proteins of the G2a and G2b subtypes. We demonstrate that the cross-protection between strains G2a and G2b is poor and that this bivalent subunit vaccine protects piglets from viral attack by inducing both active and passive immunity. This study emphasizes the effectiveness of the PEDV G2a/G2b-S bivalent subunit vaccine and provides a feasible method for the development of efficient PEDV vaccines.
Small molecule produced by
Photorhabdus
interferes with ubiquinone biosynthesis in Gram-negative bacteria
Authors: Bargabos Rachel , Iinishi Akira , Hawkins Bryson , Privalsky Thomas , Pitt Norman , Son Sangkeun , Corsetti Rachel , Gates Michael F. , Miller Ryan D. , Lewis Kim
Published: September 2024

We report the identification of 3,6-dihydroxy-1,2-benzisoxazole (DHB) in a screen of
Photorhabdus
and
Xenorhabdus
, whose symbiotic relationship with eukaryotic nematodes favors secondary metabolites that meet several requirements matching those for clinically useful antibiotics. DHB is produced by
Photorhabdus laumondii
and is selective against the Gram-negative species
Escherichia coli, Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae, Proteus mirabilis,
and
Acinetobacter baumannii
. It is inactive against anaerobic gut bacteria and nontoxic to human cells. Mutants resistant to DHB map to the ubiquinone biosynthesis pathway. DHB binds to 4-hydroxybenzoate octaprenyltransferase (UbiA) and prevents the formation of 4-hydroxy-3-octaprenylbenzoate. Remarkably, DHB itself is prenylated, forming an unusable chimeric product that likely contributes to the toxic effect of this antimicrobial. DHB appears to be both a competitive enzyme inhibitor and a prodrug; this dual mode of action is unusual for an antimicrobial compound.

IMPORTANCE

The spread of resistant pathogens has led to the antimicrobial resistance crisis, and the need for new compounds acting against Gram-negative pathogens is especially acute. From a screen of
Photorhabdus
symbionts of nematodes, we identified 3,6-dihydroxy-1,2-benzisoxazole (DHB) that acts against a range of Gram-negative bacteria, including
Escherichia coli
,
Enterobacter cloacae
,
Klebsiella pneumoniae
, and
Acinetobacter baumannii
. DHB had previously been isolated from other bacterial species, but its mechanism of action remained unknown. We show that DHB is unique among antimicrobials, with dual action as an inhibitor of an important enzyme, UbiA, in the biosynthesis pathway of ubiquinone and as a prodrug. DHB is a mimic of the natural substrate, and UbiA modifies it into a toxic product, contributing to the antimicrobial action of this unusual antibiotic. We also uncover the mechanism of DHB selectivity, which depends on a particular fold of the UbiA enzyme.
Time-resolved multi-omics reveals diverse metabolic strategies of
Salmonella
during diet-induced inflammation
Authors: Kokkinias Katherine , Sabag-Daigle Anice , Kim Yongseok , Leleiwi Ikaia , Shaffer Michael , Kevorkian Richard , Daly Rebecca A. , Wysocki Vicki H. , Borton Mikayla A. , Ahmer Brian M. M. , Wrighton Kelly C.
Published: September 2024

With a rise in antibiotic resistance and chronic infection, the metabolic response of
Salmonella enterica
serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. In this study, we use a multi-omics approach to identify the metabolic response of
Salmonella enterica
serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing
Salmonella
gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation in high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity in samples based on
Salmonella
ribosomal activity, which is separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expressions descriptive of each phase. Surprisingly, we identified genes associated with host cell entry expressed throughout infection, suggesting subpopulations of
Salmonella
or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of
Salmonella
to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection.

IMPORTANCE

Identifying novel therapeutic strategies for
Salmonella
infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts toward Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for
Salmonella
. We observed differential gene expression across infection phases in mice over time on a high-fat diet. Together, these findings reveal the metabolic tuning of
Salmonella
to dietary and temporal perturbations. Research like this, which explores the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.
Development and application of a rapid visual detection technique for VanA gene in vancomycin-resistant
Enterococcus faecium
Authors: Ji Tuo , Wang Wenjun , Wang Li , Gao Yuzhi , Wang Yan , Gao Xuzhu
Published: September 2024

The objective of this study was to establish a rapid visual diagnosis method for vancomycin-resistant
Enterococcus faecium
(VREFm) based on multienzyme isothermal rapid amplification (MIRA) combined with lateral flow strips (LFSs). The MIRA primers and probes were specifically designed to maintain the sequence of the VanA gene of VREFm. We optimized the reaction time and temperature and thoroughly assessed the specificity and sensitivity of the MIRA-LFS system. We also compared the MIRA-LFS method with the polymerase chain reaction (PCR) assay and the disc diffusion method. We then evaluated the MIRA-LFS assay for consistency testing and clinical application. The MIRA-LFS technique completed the amplification process within 30 min, and the results were observed on LFS. The method demonstrated high sensitivity, with a minimum detection limit of 1.066 CFU/µL for VREFm and exhibited specificity without cross-reactivity with other pathogenic bacteria. When applied to the detection of clinical samples, the method exhibited consistency with the PCR and agar dilution methods. The combined use of MIRA and LFS in this study facilitates simplifying the workflow for detecting VREFm, which is of great significance for rapidly detecting the enterococcal infections and preventing and controlling the nosocomial infections.

IMPORTANCE

One of the key approaches to treating and controlling vancomycin-resistant
Enterococcus faecium
(VREFm) is an accurate and rapid diagnosis. To achieve this goal, a simple and rapid method must be constructed for immediate detection in the field. Multienzyme isothermal rapid amplification (MIRA) is an isothermal rapid amplification method that allows amplification reactions to be completed under room temperature conditions. When combined with lateral flow strips (LFSs), MIRA-LFS enables the rapid detection of pathogenic microorganisms. However, the MIRA method often produces false signals. These false signals are eliminated by using base mismatches introduced in primers and probes. The MIRA-LFS system was constructed with high specificity and sensitivity for the detection of VREfm, without the limitation of sophisticated instruments. This enables the prompt formulation of diagnostic and therapeutic decisions.
Inosine reverses multidrug resistance in Gram-negative bacteria carrying mobilized RND-type efflux pump gene cluster
tmexCD-toprJ
Authors: Li Fulei , Xu Tianqi , Fang Dan , Wang Zhiqiang , Liu Yuan
Published: September 2024

Antimicrobial resistance is rapidly increasing worldwide, highlighting the urgent need for pharmaceutical and nonpharmaceutical interventions to tackle different-to-treat bacterial infections. Tigecycline, a semi-synthesis glycylcycline for parenteral administration, is widely recognized as one of the few effective therapies available against pan-drug resistant Gram-negative pathogens. Regrettably, the efficacy of multiple drugs, including tigecycline, is currently being undermined due to the emergence of a recently discovered mobilized resistance-nodulation-division-type efflux pump gene cluster
tmexCD1-toprJ1
. Herein, by employing untargeted metabolomic approaches, we reveal that the expression of
tmexCD1-toprJ1
disrupts bacterial purine metabolism, with inosine being identified as a crucial biomarker. Notably, the supplementation of inosine effectively reverses tigecycline resistance in
tmexCD1-toprJ1
-positive bacteria. Mechanistically, exogenous inosine enhanced bacterial proton motive force, which promotes the uptake of tigecycline. Furthermore, inosine enhances succinate biosynthesis by stimulating the tricarboxylic acid cycle. Succinate interacts with the two-component system EnvZ/OmpR and upregulates OmpK 36, thereby promoting the influx of tigecycline. These actions collectively lead to the increased intracellular accumulation of tigecycline. Overall, our study offers a distinct combinational strategy to manage infections caused by
tmexCD-toprJ
-positive bacteria.

IMPORTANCE

TMexCD1-TOprJ1, a mobilized resistance-nodulation-division-type efflux pump, confers phenotypic resistance to multiple classes of antibiotics. Nowadays,
tmexCD-toprJ
has disseminated among diverse species of clinical pathogens, exacerbating the need for novel anti-infective strategies. In this study, we report that
tmexCD1-toprJ1
-negative and -positive bacteria exhibit significantly different metabolic flux and characteristics, especially in purine metabolism. Intriguingly, the addition of inosine, a purine metabolite, effectively restores the antibacterial activity of tigecycline by promoting antibiotic uptake. Our findings highlight the correlation between bacterial mechanism and antibiotic resistance, and offer a distinct approach to overcome
tmexCD-toprJ
-mediated multidrug resistance.
Supplemental Material: Seawater sulfate dynamics and a new tipping point in the Earth system
Authors: Fakhraee Mojtaba , Bauer Kohen W. , Crowe Sean A.
Published: September 2024

Text, Tables S1–S3, and Figures S1–S3.  
Supplemental Material: Subduction retreat recorded in the southern Beishan orogenic collage of the Central Asian Orogenic Belt: New evidence from deep seismic reflection profiling
Authors: Xiong Xiaosong , al. et
Published: September 2024

Zircon ages.
High-intensity interval training for cardiometabolic health in adults with metabolic syndrome: a systematic review and meta-analysis of randomised controlled trials
Authors: Poon Eric Tsz-Chun , Wongpipit Waris , Li Hong-Yat , Wong Stephen Heung-Sang , Siu Parco M , Kong Alice Pik-Shan , Johnson Nathan A
Published: September 2024

Objective

To assess the effectiveness of high-intensity interval training (HIIT) compared with traditional moderate-intensity continuous training (MICT) and/or non-exercise control (CON) for modification of metabolic syndrome (MetS) components and other cardiometabolic health outcomes in individuals with MetS.

Design

Systematic review and meta-analysis

Data sources

Five databases were searched from inception to March 2024.

Study appraisal and synthesis

Meta-analyses of randomised controlled trials (RCTs) comparing HIIT with MICT/CON were performed for components of MetS (waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting blood glucose (BG)) and clinically relevant cardiometabolic health parameters. Subgroup moderator analyses were conducted based on the intervention duration and HIIT volume.

Results

Out of 4819 studies, 23 RCTs involving 1374 participants were included (mean age: 46.2–67.0 years, 55% male). HIIT significantly improved WC (weighted mean difference (WMD) –4.12 cm, 95% CI –4.71 to –3.53), SBP (WMD –6.05 mm Hg, 95% CI –8.11 to –4.00), DBP (WMD –3.68 mm Hg, 95% CI –5.70 to –1.65), HDL-C (WMD 0.12 mmol/L, 95% CI 0.04 to 0.20), TG (WMD –0.34 mmol/L, 95% CI –0.41 to –0.27) and BG (WMD –0.35 mmol/L, 95% CI –0.54 to –0.16) compared with CON (all p<0.01). HIIT approaches demonstrated comparable effects to MICT across all parameters. Subgroup analyses suggested that HIIT protocols with low volume (ie, <15 min of high-intensity exercise per session) were not inferior to higher volume protocols for improving MetS components.

Conclusion

This review supports HIIT as an efficacious exercise strategy for improving cardiometabolic health in individuals with MetS. Low-volume HIIT appears to be a viable alternative to traditional forms of aerobic exercise.
Risk of neuropsychiatric adverse events associated with montelukast use in children and adolescents: a population-based case-crossover study
Authors: Kim Jae Won , Kim Mideum , Seo Min Sook , Shin Ju-Young
Published: September 2024

Purpose

Montelukast is used extensively in children and adolescents for allergic rhinitis and asthma. However, concerns have been raised regarding the increased risk of neuropsychiatric adverse events (NPAEs) associated with montelukast use. Therefore, our case-crossover study was conducted to observe whether there is an increased risk of NPAEs associated with montelukast use in children and adolescents.

Materials and methods

A population-based case-crossover study using the customised Health Insurance Review and Assessment (HIRA) dataset was conducted. Paediatric patients aged between 0 and 19 years diagnosed with allergic rhinitis and/or asthma with a history of at least one montelukast prescription between 1 January 2018 and 31 December 2021 were included. Exposure to montelukast was assessed during 3-, 7-, 14-, 28- and 56-day hazard periods prior to each patient’s NPAE. Stratified analyses according to age group, gender and season for the risk of NPAEs associated with montelukast use in the previous 7 days and 14 days were performed, respectively. Conditional logistic regression analysis was used to calculate adjusted ORs (aORs) with their corresponding 95% CIs, adjusting for concomitant medications.

Results

A total of 161 386 paediatric patients was identified. An increased risk of NPAEs associated with montelukast was found in all time window periods, including 3-day (aOR 1.28, 95% CI 1.24 to 1.32), 7-day (aOR 1.29, 95% CI 1.26 to 1.33), 14-day (aOR 1.34, 95% CI 1.31 to 1.37), 28-day (aOR 1.38, 95% CI 1.36 to 1.41) and 56-day (aOR 1.21, 95% CI 1.19 to 1.22) preceding hazard periods compared with use in the four control periods.

Conclusion

Children and adolescents with allergic rhinitis and/or asthma should be prescribed montelukast with caution considering clinical benefits.
Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy
Authors: Zhou Qiming , Lei Linhan , Cheng Junhong , Chen Junyou , Du Yuyang , Zhang Xuehua , Li Qing , Li Chuangen , Deng Haijun , Wong Chi Chun , Zhuang Baoxiong , Li Guoxin , Bai Xiaowu
Published: September 2024

Background

Tumourigenesis in right-sided and left-sided colons demonstrated distinct features.

Objective

We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis.

Design

Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results.

Results

Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11
+
epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer.

Conclusion

Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.
Post-radiation optic neuropathy
Authors: Margolin Edward , Handzic Armin
Published: September 2024

A middle-aged man developed subacute painless visual loss in the left eye leading to no light perception, and 2 weeks later developed subacute visual loss in the right eye to no light perception. He had a history of resected pituitary macroadenoma. MR scan of brain and orbits with contrast showed short prechiasmatic segments of enhancement in each optic nerve. Cerebrospinal fluid analysis was normal. Extensive diagnostic work-up was unrevealing but review of medical records identified a history of prophylactic radiotherapy to the pituitary gland following pituitary macroadenoma resection 1.5 years before. We diagnosed post-radiation optic neuropathy. This condition typically occurs 1–1.5 years after the radiotherapy given near the visual pathway. Its pathophysiology presumably relates to an endotheliopathy of the vasa nervosum supplying the optic nerve due to free radical accumulation following radiotherapy. It manifests with unilateral or bilateral sequential severe visual loss with imaging showing characteristic enhancement of the short segment of the affected intracranial optic nerve. There is no available definitive treatment, but hyperbaric oxygen therapy, given shortly after onset of visual loss, is a promising treatment.
Youth and young adult flavour expectancies for new ‘non-menthol’ cigarettes introduced following California’s ban on flavoured tobacco products
Authors: Kreslake Jennifer M , Cordova Jamie , Seidenberg Andrew B , Ali Fatma Romeh M , Schillo Barbara , Marynak Kristy
Published: September 2024

Background

Following California’s statewide law prohibiting the sale of flavoured tobacco products, some cigarette brands introduced new variants advertised as non-menthol, yet featuring design and text commonly found in menthol cigarette marketing.

Methods

Data are from the February–May 2023 wave of the Tobacco Epidemic Evaluation Network (TEEN+) national probability-based survey (aged 13–25 years). Respondents (N=10 217) were shown images of two (of four) ‘new non-menthol’ brand ads or packaging and two comparators (‘classic’ non-menthol and menthol cigarette brands). Respondents reported expected taste of each (no or any minty/menthol taste; ‘don’t know’). Multinomial regression models tested associations between predictors (age, gender identity, race and ethnicity, perceived financial situation, smoking status) and expectation of minty/menthol taste.

Results

Younger age was associated with expectations of minty/menthol taste, controlling for covariates. Respondents aged 13–17 years had greater odds of expecting minty/menthol taste than no minty/menthol taste for all tested new non-menthol brands (Camel Crush Oasis adjusted OR (aOR): 1.30, p<0.05; Camel Crisp aOR: 1.47, p<0.001; Kool Non-Menthol Blue aOR: 1.27, p<0.05; Kool Non-Menthol Green aOR: 1.43, p<0.01), compared to respondents aged 21 and older. Respondents aged 18–20 years had greater odds of reporting minty/menthol expectancies than no minty/menthol expectancies for Camel Crush Oasis (aOR: 1.35, p<0.05) and Kool Non-Menthol Green (aOR: 1.29, p<0.05) compared to those aged 21–25 years. Compared to non-Hispanic white respondents, non-Hispanic Asian respondents had greater odds of expecting minty/menthol taste than no minty/menthol taste for Camel Crush Oasis (aOR: 1.89, p<0.01), Kool Non-Menthol Blue (aOR: 1.88, p<0.01) and Kool Non-Menthol Green (aOR: 1.72, p<0.05).

Discussion

Younger age was associated with expectations of new non-menthol cigarettes having a minty/menthol taste. Results raise concerns regarding the potential appeal of these products to youth and young adults.
Pulmonary fibrosis and lung cancer: an analysis of the Clinical Practice Research Datalink linked to the National Cancer Registration Dataset
Authors: Gonnelli Francesca , Kaur Jaspreet , Bonifazi Martina , Baldwin David , O’Dowd Emma , Hubbard Richard
Published: September 2024

We quantified the proportion of diagnoses of pulmonary fibrosis (PF) among 25 136 people with lung cancer and 250 583 matched controls and compared the natural history of lung cancer in people with and without PF. Diagnoses of PF were more common in people with lung cancer than those without (1.5% vs 0.8%, OR 1.97; 95% CI 1.77 to 2.21). Within people with PF, squamous cell carcinoma was more (22.9% vs 19.1%), and adenocarcinoma was less common (18.0% vs 21.3%). People with PF were less likely to have stage 4 disease at diagnosis (OR 0.43, 95% CI 0.28 to 0.65) but their survival was worse.
Mononuclear palladacycles versus acyclic analogues: a structure and reactivity comparison
Authors: Li Hanxiang , Wu Shih-Chang , Chitanda Jackson M. , Quail J. Wilson , Foley Stephen R.
Published: September 2024

The metallocyclic ring in mononuclear iminoisoindoline-based palladacycle [(κ2-iminoisoidoline)PdCl(PCy3)] (3) can be ring opened by coordination of phosphine to form the trans bis(phosphine) iminoisoindoline-based palladium(II) complex [(η1-iminoisoidoline)PdCl(PCy3)2] (4) where the η1-iminoisoindoline is coordinated only by an Ar–Pd bond. The ring-opened analogue showed significantly higher coupling activity in Suzuki-Miyaura reactions with aryl chlorides than any iminoisoindoline-based palladacycle studied to date. These results are compared to existing mononuclear palladacycles and reported acyclic analogues.
Variability in somatic growth over time and space determines optimal season-opening date in the Oregon ocean shrimp (Pandalus jordani) fishery
Authors: Oken Kiva L. , Groth Scott D. , Holland Daniel S. , Punt André E. , Ward Eric J.
Published: September 2024

Growth variability is a key contributor to the dynamic productivity of populations. Thus, better understanding and accounting for variation in growth can improve both tactical and strategic management. Using ocean shrimp ( Pandalus jordani) from the U.S. West Coast as a case study, we demonstrate interactions between growth and optimal fishery opening dates. While the fishery opens on 1 April, industry often delays fishing to minimize catches of small shrimp. Understanding drivers of size-at-recruitment can help managers optimize opening dates and shrimpers plan their participation in this and other fisheries. Using three decades of fishery-dependent sampling, we built a spatially, temporally, and environmentally explicit Bayesian state-space model for shrimp size-at-age. Model outputs were then used to parameterize a revenue-per-recruit model and explore how variability in size-at-recruitment impacted optimal opening dates. Shrimp recruited at smaller sizes farther north. Delaying opening would likely benefit shrimpers in areas and years with smaller shrimp and higher fishing mortality. Broadly, choosing when to open the fishery is a complex decision requiring understanding of growth, but also recruitment, economic incentives, and life history.
Do Azospirillum brasiliense and Chlorella sp. microalgae benefit the production of Hymenaea courbaril L. seedlings?
Authors: Biazatti Renan Marré , Santos Silvia Correa , Santos Cleberton Correia , Pinheiro Bruno Lenhart , de Carvalho Rafael Lima , de Medeiros Elias Silva , Scalon Silvana de Paula Quintão , Torales Elissandra Pacito
Published: September 2024

The use of Azospirillum brasiliense and Chlorella sp. has gained popularity in agriculture and forestry due to their benefits to plants. These two biological solutions have demonstrated potential to improve the performance and sustainability of crops and forest species, opening new perspectives for agriculture, and the recovery of degraded areas. Given the importance of establishing management strategies for seedling production and that information on forest essences is insufficient, the aim of this study was to evaluate the effect of intervals of Chlorella sp . microalgae application and inoculation with A. brasiliense doses on the growth and quality of Hymenaea courbaril L. seedlings. The experiment was conducted in a randomized block experimental design, and treatments were arranged in a 5 × 4 factorial scheme, with four replicates, testing five A. brasiliense doses: 0, 3, 6, 9, and 12 mL/plant and four intervals of Chlorella sp. microalgae application: single application and every 7, 14, and 21 days after transplanting, for 120 days. Growth and photosynthetic parameters were evaluated. Inoculation with 6 and 9 mL of Azospirillum brasiliense, regardless of Chlorella sp. microalgae application favored the growth of H. courbaril seedlings. Chlorella sp. microalgae application at intervals of 14 and 21 days favored the responses of seedlings inoculated with A. brasilienses. The association between Azospirillum brasiliense and Chlorella sp. promoted gains in seedling production and quality.
Interpolating gauge-fixing for Yang–Mills–Chern–Simons theory in $$D=3$$
Authors: Azevedo Daniel O. R. , Del Cima Oswaldo M. , Dias Thadeu S. , Pereira Emílio D.
Published: September 2024

The Yang–Mills–Chern–Simons theory in three-dimensional Minkowski space-time is studied in a gauge-fixing scheme which interpolates between the covariant gauge and light-cone gauge, the interpolating gauge-fixing. The ultraviolet finiteness of the theory is proved via the Becchi–Rouet–Stora (BRS) algebraic renormalization procedure, which allows us to demonstrate the vanishing of all $$\beta $$
β
-functions and all anomalous dimensions to all orders in perturbation theory.
SIGACT News Online Algorithms Column 42
Authors: van Stee Rob
Published: September 2024

For this issue, I am pleased to present a tutorial by Will Ma on using randomized rounding to design online policies. Randomized rounding has of course been used extensively in the design of approximation algorithms and also to approximately solve sequential stochastic optimization problems. Will describes several examples that show how randomized rounding can be used in this context.

As always, I would like to invite more contributions to this column, be it surveys, conference reports, or technical articles related to online algorithms and competitive analysis. If you are considering becoming a guest writer, don't hesitate to mail me at rob.vanstee@uni-siegen.de.
Combining Radiomics and Autoencoders to Distinguish Benign and Malignant Breast Tumors on US Images
Authors: Magnuska Zuzanna Anna , Roy Rijo , Palmowski Moritz , Kohlen Matthias , Winkler Brigitte Sophia , Pfeil Tatjana , Boor Peter , Schulz Volkmar , Krauss Katja , Stickeler Elmar , Kiessling Fabian
Published: September 2024

Combining classical radiomics and autoencoder-based features extracted from tumor bounding boxes improves US-based categorization of benign and malignant breast tumors compared with segmentation-based approaches.
Development of Multiple Electrospray Nozzles for Fabricating Catalyst Layers of Polymer Electrolyte Fuel Cells
Authors: Yoneyama Chisami , Tamoto Kayoko , Miyamoto Yuhei , Sugiyama Tomio , Nagasaka Takumi , Taguchi Chihiro , Yoneyama Shimao , Uchida Makoto
Published: September 2024

The electrospray (ES) method can be used to make porous, high-performance and low-Pt-loading catalyst layers (CLs). In our group’s previous work, we succeeded in improving the cell performance in low-Pt-loading polymer electrolyte fuel cell cathode CLs by the use of a single-pin-nozzle ES method. However, the coating amount of the ES method is too low to be applied in mass production. In the present work, we have developed multi-pin nozzles. We started with the examination of two single-pin nozzles and confirmed that the ES method with plural nozzle pins was possible. We created a seven-pin nozzle as the first multi-pin nozzle. The uniformity of both the amount and scattering direction of the ink emission from that nozzle was deficient. We found that electrostatic-field control pins and plate were effective in correcting the behavior. Next, we created a 12-pin nozzle that was also equipped with electrostatic-field control pins and plate. We examined the length of the electrostatic-field control pins and the pin pitch with that nozzle. Finally, we increased the number of the nozzle pins to 72. The cathode CLs coated with that nozzle exhibited higher uniformity and cell performance in comparison with CLs coated by use of the pulse-swirl-spray method.
Rapid Detection of Ultralow H2S Concentration with on-chip Fabrication of SnO2-based Gas Sensors by Direct Electrodeposition from Non-Aqueous Solvents
Authors: Do Van Kiem , Van Hieu Nguyen , Yang Thomas C-K , Le Manh Tu
Published: September 2024

Hydrogen sulfide (H2S) causes significant impacts on human health and the environment due to its highly toxic properties. Thus, the design and development of gas sensors to detect and monitor H2S (especially at extremely low concentrations) are challenging tasks for scientists. In this work, SnO2 gas sensors were successfully synthesized directly on a chip by Sn electrodeposition from ethylene glycol solutions + a post-treatment (calcination) stage (to form and stabilize SnO2). Mechanisms and kinetics of Sn electrodeposition on Pt microelectrodes were thoroughly studied using electrochemical techniques. These fabricated gas sensors exhibit a high selectivity toward H2S gas and an effective response to low-level concentrations of H2S in the range of 0.1 ppm–1 ppm at different working temperatures. The influence of electrodeposition conditions and calcination temperatures on the gas response of sensors were also examined. The results have verified that the electrodeposition method from ethylene glycol solutions is promising for the fabrication of ultrasensitive on-chip gas sensors.
Activation of platelets and the complement system in mice with Schistosoma-induced pulmonary hypertension
Authors: Mickael Claudia , Jordan Mariah , Posey Janelle N. , Tuder Rubin M. , Nozik Eva S. , Thurman Joshua M. , Stenmark Kurt R. , Graham Brian B. , Delaney Cassidy A.
Published: September 2024

Schistosomiasis-induced pulmonary hypertension (PH) is a significant global health burden, yet the underlying mechanisms remain poorly understood. We demonstrate that Schistosoma exposure leads to platelet accumulation in the lung and platelet activation. We observed increased plasma levels of C3a and C5a, indicative of complement system activation, and elevated expression of platelet complement proteins and receptors. These findings underscore the role of platelets and complement in the inflammatory responses associated with Schistosoma-induced PH.
Cigarette smoking prolongs inflammation associated with influenza infection and delays its clearance in mice
Authors: Vlasma Jelmer R. , van der Veen Tineke Anienke , de Jager Marina H. , Nawijn Martijn C. , Brandsma Corry-Anke , Melgert Barbro N.
Published: September 2024

In this study, we describe how cigarette smoke exposure modulates immune responses against influenza in mice over time. Using a unique model that continues smoke exposure after infection, we demonstrate that inflammation is prolonged and viral clearance is delayed. This clinically relevant model for smokers that contract influenza is well positioned to investigate interactions between smoke and influenza infection.
Association Between Initial Corticosteroid Regimen and Treatment Response Time in Acetylcholine Receptor Antibody–Positive Myasthenia Gravis
Authors: Kim Jinhee , Park Hyung Jun , Kim Seung Woo , Shin Ha Young
Published: September 2024

Background: Corticosteroids remain the cornerstone in the management of myasthenia gravis (MG). Initiation of corticosteroid treatment at a high dose and subsequently decreasing the dose or gradual escalation from a low dose is recommended. We aimed to investigate the association between the initial corticosteroid regimen and treatment response.

Methods: A retrospective study was conducted on 234 acetylcholine receptor (AChR) antibody (Ab)–positive MG patients who visited our institution between January 2010 and February 2023. Patients were grouped based on prednisolone dosages received: initial high (IH, ≥50 mg/day) or initial low (IL, ≤20 mg/day). Time to initial improvement and the achievement of minimal manifestation (MM) status were the main outcomes.

Results: Of the 234 patients, 135 were classified as IH and 99 as IL group. The IH group demonstrated a faster onset of improvement compared with the IL group (20.0 [16.0–29.0] vs. 40.0 [27.0–84.0] days), with the IH group being a significant prognostic factor for initial improvement (HR, 2.44; 95% CI, 1.76–3.39). However, the IH group had a higher incidence of steroid‐induced exacerbation (51.9% vs. 2.0%, p < 0.001). No significant difference between the IH and IL groups was found in terms of the proportion of patients achieving MM or the time to achieve MM within the first year after treatment initiation.

Conclusion: While an initial high dose of corticosteroid treatment accelerated the onset of therapeutic responses in patients with AChR Ab–positive MG, it was associated with a higher cumulative steroid dose and an increased risk of steroid‐induced exacerbations.
Mechanisms Underlying the Overturning Failure of Terraced Field Side Walls Due to Expansive Soil Swelling During Layer‐By‐Layer Saturation
Authors: Pan Junyi , Li RongJian , Yang Suiyuan , Fang Yahong , Bai Weishi , Wang Laizhu , Li Haitao
Published: September 2024

The stability of side walls in terraced fields constructed within expansive soil regions represents a critical challenge, often leading to structural failure due to the unique wetting–swelling behavior of the soil. This study employs a comprehensive approach, integrating analytical and numerical methods to elucidate the mechanism of overturning failure attributed to the swelling effect of expansive soil under conditions of layer‐by‐layer saturation. Initially, the earth pressure acting on side walls, constructed from fiber ecological bags, is assessed in their natural, unsaturated state using Bishop’s formula for unsaturated shear strength. The study further explores the failure mode through one‐dimensional analytical analysis, focusing on the horizontal and unrestrained expansion of expansive soil during progressive saturation. Subsequently, the deformation of the side wall and the swelling effect of the soil are numerically evaluated. This is achieved by analogizing the wetting–swelling deformation field in expansive soil to an equivalent temperature field, thereby facilitating the use of finite element numerical simulation to investigate the overturning failure mechanism. Findings indicate that in the natural unsaturated state, the side walls remain stable under no earth pressure. However, as saturation depth attains a critical depth of 1.4 m during layer‐by‐layer saturation, the upper wall rotates outward in the form of local overturning failure, and the corresponding infiltration saturation depth is the critical depth for the local instability of the side wall. The investigation identifies the wetting–swelling effect as the predominant factor leading to the structural failure of side walls in terraced fields situated in expansive soil areas. Moreover, a critical infiltration saturation depth of 2.6 m is determined, beyond which the stability of the side walls is compromised. This research contributes significantly to the understanding of the failure mechanisms affecting terraced agricultural infrastructures in expansive soil regions, offering a theoretical foundation for the development of more resilient construction strategies.
Recalibrating the Genetics and Epidemiology of Colorectal Cancer Consortium Environmental Risk Score for Use in US Veterans
Authors: Williams April R. , Redding Thomas S. , Sullivan Brian A. , Baidya Robin N. , Ear Belinda , Cho Kelly , Ivey Kerry L. , Williams Christina D. , Dominitz Jason A. , Lieberman David , Hauser Elizabeth R. ,   on behalf of the VA Million Veteran Program
Published: September 2024

Background:

Risk for colorectal cancer may accumulate through multiple environmental factors. Understanding their effects, along with genetics, age, and family history, could allow improvements in clinical decisions for screening protocols. We aimed to extend the previous work by recalibrating an environmental risk score (e-Score) for colorectal cancer among a sample of US veteran participants of the Million Veteran Program.

Methods:

Demographic, lifestyle, and colorectal cancer data from 2011 to 2022 were abstracted from survey responses and health records of 227,504 male Million Veteran Program participants. Weighting for each environmental factor’s effect size was recalculated using Veterans Affairs training data to create a recalibrated e-Score. This recalibrated score was compared with the original weighted e-Score in a validation sample of 113,752 (n cases = 590). Nested multiple logistic regression models tested associations between quintiles for recalibrated and original e-Scores. Likelihood ratio tests were used to compare model performance.

Results:

Age (P < 0.0001), education (P < 0.0001), diabetes (P < 0.0001), physical activity (P < 0.0001), smoking (P < 0.0001), NSAID use (P < 0.0001), calcium (P = 0.015), folate (P = 0.020), and fruit consumption (P = 0.019) were significantly different between colorectal cancer case and control groups. In the validation sample, the recalibrated e-Score model significantly improved the base model performance (P < 0.001), but the original e-Score model did not (P = 0.07). The recalibrated e-Score model quintile 5 was associated with significantly higher odds for colorectal cancer compared with quintile 1 (Q5 vs. Q1: 1.79; 95% CI, 1.38–2.33).

Conclusions:

Multiple environmental factors and the recalibrated e-Score quintiles were significantly associated with colorectal cancer cases.

Impact:

A recalibrated, veteran-specific e-Score could be used to help personalize colorectal cancer screening and prevention strategies.
Disseminated Mucormycosis and T-Cell-Depleted Allogeneic Stem Cell Transplantation: An Unusual Case Study
Authors: Dragoi Oana Diana , Shah Mili , Potter Victoria , Avenoso Daniele , Krishnamurthy Pramila , Abdolrasouli Alireza , Schelenz Silke , Chandra Julie , Mehra Varun
Published: September 2024

Introduction: Invasive fungal infections are a primary cause of morbidity and mortality in patients with haematological malignancies. Case Presentation: We describe an unusual clinical and radiological presentation of invasive mucormycosis (IM) in a 69-year-old patient with relapsed acute myeloid leukaemia. The patient was diagnosed with disseminated IM with involvement of the central nervous system in an atypical location, lung, spleen, muscle, bone, and heart, after having completed induction and bridging chemotherapy to allogeneic haematopoietic stem cell transplant (HSCT). Her clinical presentation was atypical with mild neurological symptoms slowly progressing over 2 months and without appropriate signs of systemic inflammation. Mucorales was eventually confirmed from bronchoalveolar lavage and subdural collection. Conclusion: This report highlights the difficult challenges of managing disseminated IM in an immunocompromised patient, where close multidisciplinary specialist care enabled successful treatment, followed by T-cell-depleted allogeneic HSCT for a high-risk haematological malignancy.
Elevated Serum IL-17A in Kawasaki Disease Patients Predicts Responsiveness to Intravenous Immunoglobulin Therapy
Authors: Lu Yan , Hu Fang-Qi
Published: September 2024

Introduction: This study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients. Methods: A retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). Results: A total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780. Conclusion: Serum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.
Efficacy of Acetylcholinesterase Inhibitors in the Logopenic Variant of Primary Progressive Aphasia
Authors: Carrier-Auclair Julie , Lavoie Monica , Tastevin Maud , Laforce Jr. Robert
Published: September 2024

Introduction: For over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer’s disease (AD). Several meta-analyses have supported their effectiveness in various neurocognitive, functional, and behavioral aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA), also named language variant AD, are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their evolution on the MMSE, and other functional and behavioral parameters, to that of treated amnestic AD patients. Methods: A retrospective chart review was performed in 45 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar in terms of age, level of education, and onset of symptoms. Drug history and MMSE scores, as well as functional (activities of daily living [ADLs] and instrumental activities of daily living [IADLs]), neurocognitive and neuropsychiatric symptoms were collected on several time points before and after the introduction of ChEIs. Data were analyzed using ANOVA and a generalized linear mixed model. Results: Patients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs up to 12–24 months after the introduction of ChEIs. There was a significant impact on ADLs but not IADLs and neuropsychiatric symptoms remained stable over time. Conclusion: This study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients, hence reassuring patients and their physicians.