bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term Psychodynamic Psychotherapy in Addition to Standard Medical Therapy Increases Clinical Remission in Adolescents and Young Adults with Inflammatory Bowel Disease: a Randomised Controlled Trial
Authors: Milo Francesco , Imondi Chiara , D’Amore Carmen , Angelino Giulia , Knafelz Daniela , Bracci Fiammetta , Dall’Oglio Luigi , De Angelis Paola , Tabarini Paola
Published: August 2023

Background

Inflammatory bowel diseases [IBD] are chronic and pervasive conditions of the gastrointestinal tract with a rising incidence in paediatric and young adult populations. Evidence suggests that psychological disorders might be associated with relapse of disease activity. This study aims to evaluate the efficacy of short-term psychodynamic psychotherapy [STPP] in addition to standard medical therapy [SMT] in maintaining clinical remission in adolescents and young adults [AYA] with quiescent IBD, compared with SMT alone.

Methods

A two-arm, single-centre, randomised, controlled trial was conducted in 60 IBD AYA in clinical remission. Patients were randomised to receive an 8-week STPP + SMT [n = 30] or SMT alone [n = 30]. The primary outcome was the steroid-free remission rate at 52 weeks after treatment. Secondary outcomes included the overall hospitalisation rate within 52 weeks after treatment, and medication adherence obtained from patient’s electronic medical records.

Results

Intention-to-treat analysis showed significant improvement in maintaining disease remission rates in the 8-week STPP + SMT group compared with the control one. The proportion of patients maintaining steroid-free remission at 52 weeks was higher in patients in STTP group [93.1%] compared with patients randomised to control group [64.3%; p = 0.01]. There were no significant differences in secondary outcomes, except for depression reduction in STPP + SMT group.

Conclusions

An 8-week STPP intervention in addition to SMT effectively increases the steroid-free remission rates in AYA with quiescent IBD. Results do not support effects for other secondary outcomes, except for depression reduction.
Temporal patterns of pre- and post-natal target organ damage associated with hypertensive pregnancy: a systematic review
Authors: Cutler Hannah Rebecca , Barr Logan , Sattwika Prenali Dwisthi , Frost Annabelle , Alkhodari Mohanad , Kitt Jamie , Lapidaire Winok , Lewandowski Adam James , Leeson Paul
Published: August 2023

Aims

Hypertensive pregnancy is associated with increased risks of developing a range of vascular disorders in later life. Understanding when hypertensive target organ damage first emerges could guide optimal timing of preventive interventions. This review identifies evidence of hypertensive target organ damage across cardiac, vascular, cerebral, and renal systems at different time points from pregnancy to postpartum.

Methods and results

Systematic review of Ovid/MEDLINE, EMBASE, and ClinicalTrials.gov up to and including February 2023 including review of reference lists. Identified articles underwent evaluation via a synthesis without meta-analysis using a vote-counting approach based on direction of effect, regardless of statistical significance. Risk of bias was assessed for each outcome domain, and only higher quality studies were used for final analysis. From 7644 articles, 76 studies, including data from 1 742 698 pregnancies, were identified of high quality that reported either blood pressure trajectories or target organ damage during or after a hypertensive pregnancy. Left ventricular hypertrophy, white matter lesions, proteinuria, and retinal microvasculature changes were first evident in women during a hypertensive pregnancy. Cardiac, cerebral, and retinal changes were also reported in studies performed during the early and late post-partum period despite reduction in blood pressure early postpartum. Cognitive dysfunction was first reported late postpartum.

Conclusion

The majority of target organ damage reported during a hypertensive pregnancy remains evident throughout the early and late post-partum period despite variation in blood pressure. Early peri-partum strategies may be required to prevent or reverse target organ damage in women who have had a hypertensive pregnancy.
The Fish Pathogen “CandidatusClavichlamydia salmonicola”—A Missing Link in the Evolution of Chlamydial Pathogens of Humans
Authors: Collingro Astrid , Köstlbacher Stephan , Siegl Alexander , Toenshoff Elena R , Schulz Frederik , Mitchell Susan O , Weinmaier Thomas , Rattei Thomas , Colquhoun Duncan J , Horn Matthias
Published: August 2023

Chlamydiae like Chlamydia trachomatis and Chlamydia psittaci are well-known human and animal pathogens. Yet, the chlamydiae are a much larger group of evolutionary ancient obligate intracellular bacteria that includes predominantly symbionts of protists and diverse animals. This makes them ideal model organisms to study evolutionary transitions from symbionts in microbial eukaryotes to pathogens of humans. To this end, comparative genome analysis has served as an important tool. Genome sequence data for many chlamydial lineages are, however, still lacking, hampering our understanding of their evolutionary history. Here, we determined the first high-quality draft genome sequence of the fish pathogen “Candidatus Clavichlamydia salmonicola”, representing a separate genus within the human and animal pathogenic Chlamydiaceae. The “Ca. Clavichlamydia salmonicola” genome harbors genes that so far have been exclusively found in Chlamydia species suggesting that basic mechanisms important for the interaction with chordate hosts have evolved stepwise in the history of chlamydiae. Thus, the genome sequence of “Ca. Clavichlamydia salmonicola” allows to constrain candidate genes to further understand the evolution of chlamydial virulence mechanisms required to infect mammals.
The Association Between Serum Uric Acid and Cognitive Function Among Middle-Aged and Older Adults Without Hyperuricemia: The Mediating Role of Depressive Symptoms
Authors: Zhang Jiajia , Jia Xiuqin , Li Yingying , Zheng Deqiang , Guo Xiuhua , Li Haibin , Yang Qi
Published: August 2023

Background

The association between serum uric acid (SUA) and cognitive function remains unclear, especially among individuals without hyperuricemia. We examined the cross-sectional and longitudinal bidirectional associations between SUA and cognition, as well as the mediating effect of depressive symptoms among Chinese adults.

Methods

Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). SUA (continuous) and cognitive function (based on mental intactness and episodic memory) were measured at Wave 1 and Wave 3. Depressive symptoms (Center for Epidemiologic Studies Depression scale) were assessed at Wave 1. Bivariate latent change score models and mediation analysis were used to investigate these possible associations.

Results

A total of 6 236 participants free of hyperuricemia (aged 58.3 ± 8.5 years) were included. After controlling for potential confounders, the SUA level was associated with cognition at baseline (standardized r = 0.042; p = .001). Higher baseline SUA level was associated with slower subsequent cognitive decline (standardized β = 0.026; p = .027), whereas baseline cognition was not significantly associated with subsequent change in SUA (standardized β = 0.003; p = .817). In mediation analysis, baseline SUA was indirectly associated with subsequent cognition via baseline depressive symptoms (mediation effect 13.3%; p < .001).

Conclusions

Higher baseline SUA level is associated with better baseline cognition and less subsequent cognitive decline among Chinese adults without hyperuricemia. Baseline depressive symptoms may partially mediate the association between baseline SUA and later cognition. Continued research is warranted to verify these findings and elucidate the causality and underlying mechanisms.
Ultrafast track versus conventional fast track in patients undergoing cardiac surgery: a propensity score-matched analysis
Authors: Carnero-Alcázar Manuel , Beltrao-Sial Rosa , Montero-Cruces Lourdes , López-Vyzcaino Miguel , Pérez-Camargo Daniel , Sánchez Rubén , Cobiella-Carnicer Javier , Fernández-Velasco David , Maroto-Castellanos Luis C
Published: August 2023

OBJECTIVES

We aimed at comparing the risk of major adverse events and length of stay between patients undergoing ultrafast track and conventional fast track.

METHODS

Retrospective cohort study adjusted by propensity score matching, including patients operated on between March 2020 and December 2022 of any of the following: coronary, valve surgery or ascending aorta surgery. Patients were divided into 2 groups: ultrafast track: extubation in the operating room and fast track: extubation attempted in the first 6 postoperative hours. The primary objective was to compare the risk of the combined event death, lung respiratory outcomes (reintubation, mechanical ventilation longer than 24 h or pneumonia), or acute renal failure.

RESULTS

A total of 1126 patients were included. A total of 579 (51.4%) were extubated in the operating room. A total of 331 pairs were available after matching by propensity score. The risk of the primary outcome was 11.8% (n = 39) in the fast-track group and 6.3% (n = 21) in the ultrafast-track group (P = 0.013), mostly driven by lung adverse events (6.9% vs 2.4%, P = 0.011) while no significant differences were detected in the risk of death (2.4% vs 1.8%, P = 0.77) or acute renal failure (8% vs 6.3%, P = 0.56). The risk of myocardial infarction was higher in the fast-track group (2.7% vs 0%, P = 0.039). The median length of stay in the postoperative intensive care unit was longer in the fast-track group [24.7 h (interquartile range 21.5; 62.9) vs 23.5 h (interquartile range 22; 46), P = 0.015].

CONCLUSIONS

In patients undergoing cardiac surgery, extubation in the operating room is associated to a lower risk of postoperative complications (mostly driven by lung adverse events) and length of stay in intensive care unit as compared to fast track.
Economic evaluations of adult critical care pharmacy services: a scoping review
Authors: Crosby Alex , Jennings Jennifer K , Mills Anna T , Silcock Jonathan , Bourne Richard S
Published: August 2023

Objectives

To summarise the extent and type of evidence available regarding economic evaluations of adult critical care pharmacy services in the context of UK practice.

Methods

A literature search was conducted in eight electronic databases and hand searching of full-text reference lists. Of 2409 journal articles initially identified, 38 were included in the final review. Independent literature review was undertaken by two investigators in a two-step process against the inclusion and exclusion criteria; title and abstract screening were followed by full-text screening. Included studies were taken from high-income economy countries that contained economic data evaluating any key aspect of adult critical care pharmacy services. Grey literature and studies that could not be translated into the English language were excluded.

Results

The majority were before-and-after studies (18, 47%) or other observational studies (17, 45%), and conducted in North America (25, 66%). None of the included studies were undertaken in the UK. Seven studies (18%) included cost-benefit analysis; all demonstrated positive cost-benefit values for clinical pharmacist activities.

Conclusions

Further high-quality primary research focussing on the economic evaluation of UK adult critical care pharmacy services is needed, before undertaking a future systematic review. There is an indication of a cost-benefit value for critical care pharmacist activities. The lack of UK-based economic evaluations is a limitation to further development and standardisation of critical care pharmacy services nationally.
Pullback and Direct Image of Parabolic Connections and Parabolic Higgs Bundles
Authors: Alfaya David , Biswas Indranil
Published: August 2023

We provide an explicit algebraic construction—for the pullback and direct image of parabolic bundles, parabolic Higgs bundles, and parabolic connections—through nonconstant maps between compact connected Riemann surfaces. We show that these constructions preserve semistability and polystability. We also prove that these constructions are compatible with the nonabelian Hodge correspondence.
Safety and Immunogenicity of the Heterologous 2-Dose Ad26.ZEBOV, MVA-BN-Filo Vaccine Regimen in Health Care Providers and Frontliners of the Democratic Republic of the Congo
Authors: Larivière Ynke , Garcia-Fogeda Irene , Zola Matuvanga Trésor , Isekah Osang'ir Bernard , Milolo Solange , Meta Rachel , Kimbulu Primo , Robinson Cynthia , Katwere Michael , McLean Chelsea , Hens Niel , Matangila Junior , Maketa Vivi , Mitashi Patrick , Muhindo-Mavoko Hypolite , Van geertruyden Jean-Pierre , Van Damme Pierre
Published: August 2023

Background

In response to recent Ebola epidemics, vaccine development against the Zaire ebolavirus (EBOV) has been fast-tracked in the past decade. Health care providers and frontliners working in Ebola-endemic areas are at high risk of contracting and spreading the virus.

Methods

This study assessed the safety and immunogenicity of the 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo vaccine regimen (administered at a 56-day interval) among 699 health care providers and frontliners taking part in a phase 2, monocentric, randomized vaccine trial in Boende, the Democratic Republic of Congo. The first participant was enrolled and vaccinated on 18 December 2019. Serious adverse events were collected up to 6 months after the last received dose. The EBOV glycoprotein FANG ELISA (Filovirus Animal Nonclinical Group enzyme-linked immunosorbent assay) was used to measure the immunoglobulin G–binding antibody response to the EBOV glycoprotein.

Results

The vaccine regimen was well tolerated with no vaccine-related serious adverse events reported. Twenty-one days after the second dose, an EBOV glycoprotein–specific binding antibody response was observed in 95.2% of participants.

Conclusions

The 2-dose vaccine regimen was well tolerated and led to a high antibody response among fully vaccinated health care providers and frontliners in Boende.
An Aspiration to Radically Shorten Phase 3 Tuberculosis Vaccine Trials
Authors: Hill Philip C , Cobelens Frank , Martinez Leonardo , Behr Marcel A , Churchyard Gavin , Evans Tom , Fiore-Gartland Andrew J , Garcia-Basteiro Alberto L , Hanekom Willem , Rangaka Molebogeng X , Vekemans Johan , White Richard G
Published: August 2023

A new tuberculosis vaccine is a high priority. However, the classical development pathway is a major deterrent. Most tuberculosis cases arise within 2 years after Mycobacterium tuberculosis exposure, suggesting a 3-year trial period should be possible if sample size is large to maximize the number of early exposures. Increased sample size could be facilitated by working alongside optimized routine services for case ascertainment, with strategies for enhanced case detection and safety monitoring. Shortening enrolment could be achieved by simplifying screening criteria and procedures and strengthening site capacity. Together, these measures could enable radically shortened phase 3 tuberculosis vaccine trials.
Case report: doing the mesenteric twist
Authors: Holinger Courtney , Sejka Magdalena , Skidmore Adam
Published: August 2023

A 23 year old female presents with an internal hernia after undergoing a laparoscopic duodenojejunostomy for superior mesenteric artery syndrome. This is an extremely uncommon complication. On review of the literature and this case, it is hypothesized that the internal hernia happened in this case due to the longer than usual distance between the duodenojejunal flexure and the part of jejunum brought up to anastomosis.
Emergence of artemisinin-based combination treatment failure in patients returning from sub-Saharan Africa with P. falciparum malaria
Authors: Grossman Tamar , Vainer Julia , Paran Yael , Studentsky Liora , Manor Uri , Dzikowski Ron , Schwartz Eli
Published: August 2023

Background

Artemisinin-based combination therapies (ACTs) are recommended as first-line treatment against uncomplicated Plasmodium falciparum infection. Mutations in the PfKelch13 (PF3D7_1343700) gene led to resistance to artemisinin in Southeast Asia. Mutations in the Pfcoronin (PF3D7_1251200) gene confer reduced artemisinin susceptibility in vitro to an African Plasmodium strain, but their role in clinical resistance has not been established.

Methods

We conducted a retrospective observational study of Israeli travellers returning from sub-Saharan Africa with P. falciparum malaria, including patients with artemether–lumefantrine (AL) failure. Blood samples from all malaria-positive patients are delivered to the national Parasitology Reference Laboratory along with personal information. Confirmation of malaria, species identification and comparative parasite load analysis were performed using real-time PCR. DNA extractions from stored leftover samples were analysed for the presence of mutations in Pfkelch13 and Pfcoronin. Age, weight, initial parasitaemia level and Pfcoronin status were compared in patients who failed treatment vs responders.

Results

During 2009–2020, 338 patients had P. falciparum malaria acquired in Africa. Of those, 15 (24–69 years old, 14 males) failed treatment with AL. Four were still parasitemic at the end of treatment, and 11 had malaria recrudescence. Treatment failure rates were 0% during 2009–2012, 9.1% during 2013–2016 and 17.4% during 2017–2020. In all patients, the Pfkelch13 propeller domain had a wild-type sequence. We did find the P76S mutation in the propeller domain of Pfcoronin in 4/15 (28.6%) of the treatment-failure cases compared to only 3/56 (5.5%) in the successfully treated patients (P = 0.027).

Conclusion

AL treatment failure emergence was not associated with mutations in Pfkelch13. However, P76S mutation in the Pfcoronin gene was more frequently present in the treatment-failure group and merits further investigation. The increase of malaria incidence in sub-Saharan-Africa partly attributed to the COVID-19 pandemic might also reflect a wider spread of ACT resistance.
Changes in cell wall composition due to a pectin biosynthesis enzyme GAUT10 impact root growth
Authors: Dash Linkan , Swaminathan Sivakumar , Šimura Jan , Gonzales Caitlin Leigh P , Montes Christian , Solanki Neel , Mejia Ludvin , Ljung Karin , Zabotina Olga A , Kelley Dior R
Published: August 2023

Arabidopsis (Arabidopsis thaliana) root development is regulated by multiple dynamic growth cues that require central metabolism pathways such as β-oxidation and auxin. Loss of the pectin biosynthesizing enzyme GALACTURONOSYLTRANSFERASE 10 (GAUT10) leads to a short-root phenotype under sucrose-limited conditions. The present study focused on determining the specific contributions of GAUT10 to pectin composition in primary roots and the underlying defects associated with gaut10 roots. Using live-cell microscopy, we determined reduced root growth in gaut10 is due to a reduction in both root apical meristem size and epidermal cell elongation. In addition, GAUT10 was required for normal pectin and hemicellulose composition in primary Arabidopsis roots. Specifically, loss of GAUT10 led to a reduction in galacturonic acid and xylose in root cell walls and altered the presence of rhamnogalacturonan-I (RG-I) and homogalacturonan (HG) polymers in the root. Transcriptomic analysis of gaut10 roots compared to wild type uncovered hundreds of genes differentially expressed in the mutant, including genes related to auxin metabolism and peroxisome function. Consistent with these results, both auxin signaling and metabolism were modified in gaut10 roots. The sucrose-dependent short-root phenotype in gaut10 was linked to β-oxidation based on hypersensitivity to indole-3-butyric acid (IBA) and an epistatic interaction with TRANSPORTER OF IBA1 (TOB1). Altogether, these data support a growing body of evidence suggesting that pectin composition may influence auxin pathways and peroxisome activity.
HISTONE DEACETYLASE 6 interaction with ABSCISIC ACID-INSENSITIVE 5 decreases apple drought tolerance
Authors: Li Wenjie , Deng Mengting , Wang Shicong , Wang Caixia , Guo Meimiao , Song Yi , Guo Junxing , Yan Jinjiao , Ma Fengwang , Guan Qingmei , Xu Jidi
Published: August 2023

Understanding the molecular regulation of plant response to drought is the basis of drought-resistance improvement through molecular strategies. Here, we characterized apple (Malus × domestica) histone deacetylase 6 (MdHDA6), which negatively regulates apple drought tolerance by catalyzing deacetylation on histones associated with drought-responsive genes. Transgenic apple plants over-expressing MdHDA6 were less drought-tolerant, while those with down-regulated MdHDA6 expression were more drought-resistant than nontransgenic apple plants. Transcriptomic and histone 3 acetylation (H3ac) Chromatin immunoprecipitation-seq analyses indicated that MdHDA6 could facilitate histone deacetylation on the drought-responsive genes, repressing gene expression. Moreover, MdHDA6 interacted with the abscisic acid (ABA) signaling transcriptional factor, ABSCISIC ACID-INSENSITIVE 5 (MdABI5), forming the MdHDA6-MdABI5 complex. Interestingly, MdHDA6 facilitated histone deacetylation on the drought-responsive genes regulated by MdABI5, resulting in gene repression. Furthermore, a dual-Luc experiment showed that MdHDA6 could repress the regulation of a drought-responsive gene, RESPONSIVE TO DESICCATION 29A (MdRD29A) activated by MdABI5. On the one hand, MdHDA6 can facilitate histone deacetylation and gene repression on the positive drought-responsive genes to negatively regulate drought tolerance in apple. On the other hand, MdHDA6 directly interacts with MdABI5 and represses the expression of genes downstream of MdABI5 via histone deacetylation around these genes to reduce drought tolerance. Our study uncovers a different drought response regulatory mechanism in apple based on the MdHDA6-MdABI5 complex function and provides the molecular basis for drought-resistance improvement in apple.
Strategic Exploration: Pre-emption and Prioritization
Authors: Liu Qingmin , Wong Yu Fu
Published: August 2023

This paper analyses a model of strategic exploration in which competing players independently explore a set of alternatives. The model features a multiple-player multiple-armed bandit problem and captures a strategic trade-off between pre-emption—covert exploration of alternatives that the opponent will explore in the future—and prioritization—exploration of the most promising alternatives. Our results explain how the strategic trade-off shapes equilibrium behaviours and outcomes, for example, in technology races between superpowers and R&D competitions between firms. We show that players compete on the same set of alternatives, leading to duplicated exploration from start to finish, and they explore alternatives that are a priori less promising before more promising ones are exhausted. The model also predicts that competition induces players to implement unreliable technologies too early, even though they should wait for the technologies to mature. Coordinated exploration is impossible even if the alternatives are equally promising, but it can emerge in equilibrium following a phase of pre-emptive competition if there is a short deadline. With asymmetric capacities of exploration, the weak player conducts extensive instead of intensive exploration—exploring as many alternatives as the strong player does but never fully exploring any.
Detecting Air Pollution Clusters in Japan: A Spatial Analysis Approach
Authors: Dominguez Alvaro
Published: August 2023

We rely on satellite data to study the spatial distribution of air pollutants and economic activity for 1,650 municipalities of all four main islands of Japan: Honshu, Kyushu, Hokkaido, and Shikoku. Specifically, we analyze atmospheric particulate matter and ozone concentrations, as well as population density, accessibility to cities, and night lights for the above islands. We then make use of principal component analysis, spatial dependence analysis, and methods of regionalization to endogenously classify the municipalities based on their similarity in attributes and geographic location. The spatial dependence analysis provides results which show us the specific sites where the high-value clusters (hot spots) and low-value clusters (cold spots) are located. These show a high positive correlation between economic activity and air pollution. Additionally, we perform a regionalization analysis of the variables under consideration, which specifies how the four main islands can be regionalized into six to nine geographical regions or structures, each. The regionalization takes into consideration both pollution levels and economic activity. We then conclude by discussing how these different analyses can complement each other, and how they contribute in finding the locations where policies related to air quality can help in improving the quality of life of the population.
Parasitic plant–host interaction between the holoparasite Cytinus hypocistis and the shrub Cistus albidus in their natural Mediterranean habitat: local and systemic hormonal effects
Authors: Casadesús Andrea , Munné-Bosch Sergi
Published: August 2023

Mediterranean-type ecosystems provide a unique opportunity to study parasitic plant–host interactions, such as the relationship between the dominant shrub Cistus albidus L. and the root holoparasitic plant Cytinus hypocistis L. We examined this interaction (i) locally, by measuring the hormonal profiling of the interaction zone between the holoparasitic plant and the host, and (ii) systemically, by examining the hormonal profiling and physiological status of leaves from infested and uninfested plants. Furthermore, we explored how temporal variation (seasonal effects) and geographical location influenced the systemic hormonal and physiological response of leaves. Results shed light on tissue-related variations in hormones, suggesting the parasite exerted a sink effect, mainly influenced by cytokinins. Jasmonates triggered a defense response in leaves, far from the infestation point, and both jasmonates and abscisic acid (ABA) appeared to be involved in the tolerance to holoparasitism when plants were simultaneously challenged with summer drought. Parasitism did not have any major negative impact on the host, as indicated by physiological stress markers in leaves, thus indicating a high tolerance of the shrub C. albidus to the root holoparasitic plant C. hypocistis. Rather, parasitism seemed to exert a priming-like effect and some compensatory effects were observed (increased chlorophyll contents) in the host under mild climatic conditions. We conclude that (i) cytokinins, jasmonates and ABA play a role at the local and systemic levels in the response of C. albidus to the biotic stress caused by C. hypocistis, and that (ii) seasonal changes in environmental conditions and geographical location may impact holoparasitic plant-host interactions in the field, modulating the physiological response.
Fungicide Sensitivity of Fusarium oxysporum f. sp. lentis and Fusarium acuminatum Affecting Lentil in the Northern Great Plains
Authors: Bugingo Collins , Brelsford Monica , Burrows Mary
Published: August 2023

Fusarium oxysporum f. sp. lentis and F. acuminatum cause wilting and root rot in pulse crops including lentil. Fungicide seed treatments are widely used, but information about Fusarium spp. sensitivity in lentils is limited. Here, 30 F. oxysporum f. sp. lentis and 30 F. acuminatum isolates from Montana, southern Canada, North Dakota, and Washington were identified, tested for pathogenicity, and assayed for in vitro sensitivity to pyraclostrobin, prothioconazole, ipconazole, and thiophanate-methyl. F. oxysporum f. sp. lentis and F. acuminatum differed in their sensitivity to all fungicides. No resistant isolates were identified, but F. oxysporum f. sp. lentis had lower EC50 values in pyraclostrobin (averaging 0.47 μg a.i./ml) than F. acuminatum (averaging 0.89 μg a.i./ml) for mycelia assays. Both species had lower EC50 values in prothioconazole, averaging EC50 0.23 in F. oxysporum f. sp. lentis and 0.53 μg a.i./ml in F. acuminatum. F. oxysporum f. sp. lentis isolates had the lowest EC50 values on ipconazole compared to F. acuminatum (0.78 and 1.49 μg a.i./ml). The pathogens were least sensitive to thiophanate-methyl (1.74 μg a.i./ml for F. oxysporum f. sp. lentis and 1.91 μg a.i./ml for F. acuminatum). Overall sensitivity to the fungicides was higher in F. oxysporum f. sp. lentis than F. acuminatum. This study provides reference EC50 values while pointing to the possibility of differential fungicide efficacies on Fusarium spp. This will be helpful to monitor shifts in sensitivity of Fusarium spp. and devise robust root rot/wilt management approaches.
Survival Analysis as a Basis for Testing Hypotheses when Using Quantitative Ordinal Scale Disease Severity Data
Authors: Chiang K. S. , Chang Y. M. , Liu H. I. , Lee J. Y. , Jarroudi M. El , Bock C. H.
Published: August 2023

Disease severity in plant pathology is often measured by the amount of a plant or plant part that exhibits disease symptoms. This is typically assessed using a numerical scale, which allows a standardized, convenient, and quick method of rating. These scales, known as quantitative ordinal scales (QOS), divide the percentage scale into a predetermined number of intervals. There are various ways to analyze these ordinal data, with traditional methods involving the use of midpoint conversion to represent the interval. However, this may not be precise enough, as it is only an estimate of the true value. In this case, the data may be considered interval-censored, meaning that we have some knowledge of the value but not an exact measurement. This type of uncertainty is known as censoring, and techniques that address censoring, such as survival analysis (SA), use all available information and account for this uncertainty. To investigate the pros and cons of using SA with QOS measurements, we conducted a simulation based on three pathosystems. The results showed that SA almost always outperformed midpoint conversion with data analyzed using a t test, particularly when data were not normally distributed. Midpoint conversion is currently a standard procedure. In certain cases, the midpoint approach required a 400% increase in sample size to achieve the same power as the SA method. However, as the mean severity increases, fewer additional samples are needed (approximately an additional 100%), regardless of the assessment method used. Based on these findings, we conclude that SA is a valuable method for enhancing the power of hypothesis testing when analyzing QOS severity data. Future research should investigate the wider use of survival analysis techniques in plant pathology and their potential applications in the discipline.
A combination of 5/6‐nephrectomy and unilateral ureteral obstruction model accelerates progression of remote organ fibrosis in chronic kidney disease
Authors: Homma Kyoka , Enoki Yuki , Uchida Sato , Taguchi Kazuaki , Matsumoto Kazuaki
Published: August 2023

Chronic kidney disease (CKD) involves progressive renal fibrosis, which gradually reduces kidney function and often causes various complications in extrarenal tissues. Therefore, we investigated fibrogenesis in extrarenal tissues (heart, liver, and lungs) in different experimental CKD models, such as the 5/6‐nephrectomy (5/6 Nx), unilateral ureteral obstruction (UUO), and a combination (2/3 Nx + UUO). We evaluated the degree of fibrogenesis in kidneys and extrarenal tissues by histological analysis and quantification of fibrosis‐related gene and protein expression. To elucidate the fibrosis mechanisms observed in 2/3 Nx + UUO mice, we evaluated the effect of indoxyl sulfate (IS), a typical uremic toxin accumulated in CKD, and transforming growth factor‐β (TGF‐β), a fibrosis‐related factor, on fibrosis using human hepatoma (HepG2) and RAW264.7 cells. A significant decline in renal function was observed in the 5/6 Nx and 2/3 Nx + UUO models, whereas a significant increase in renal fibrosis was observed only in the obstructed kidneys. Notable amount of fibrosis was induced in the liver and heart in the 2/3 Nx + UUO model, with the induction of macrophage infiltration and increased tissue IS and TGF‐β levels. In agreement with the results of in vivo experiments, co‐stimulation with IS, TGF‐β, and macrophage‐conditioned medium increased the expression of fibrogenic genes in HepG2 cells. We demonstrated that the 2/3 Nx + UUO model induced both loss of renal function and renal fibrosis in the earlier stages, providing a novel CKD model that induces remote organ fibrosis in a shorter time.
Animal models in systemic sclerosis: an update
Authors: Bi Xiongjie , Mills Tingting , Wu Minghua
Published: August 2023

Purpose of review

Systemic sclerosis (SSc) is a multisystem autoimmune connective tissue disease characterized by early inflammation followed by excessive fibrosis in the skin and internal organs. Enhancing our comprehension of SSc pathogenesis is essential to develop effective therapeutic strategies. Animal models that mimic one or more aspects of SSc have been proven to be a valuable resource for investigating disease mechanisms. This review aims to provide an updated overview of the existing SSc animal models and the potentially relevant pathways to SSc pathogenesis.

Recent findings

This review focuses on the most recently generated and investigated animal models, which delve into novel pathways beyond existing models or employ genetic technologies to gain a deeper understanding of SSc pathogenesis including activation of early type I interferon (IFN) signaling pathway, immune cell function and pulmonary artery hypertension (PAH).

While no single animal model can fully replicate SSc, a combination of different models can offer valuable insights into the pathways involved in the onset and advancement of the SSc. These insights can prove animal models as a crutial preclinical tool for developing effective treatments for SSc.
Methods for objective assessment of skin involvement in systemic sclerosis
Authors: Desai Ruhani , Chawla Harshdeep , Larin Kirill , Assassi Shervin
Published: August 2023

Purpose of review

Skin fibrosis is the most prominent disease manifestation of systemic sclerosis (SSc). Although the treatment for other SSc manifestations has expanded over the years, there is limited progress in identifying effective treatment options for SSc skin involvement. This is in part due to limitations in the utilized outcome measures for assessment of skin fibrosis. This review focuses on different emerging assessment tools for SSc skin involvement and their potential use for clinical care and multicenter trials.

Recent findings

Durometer and other device-based methodologies requiring application of direct pressure to the affected skin have been studied in SSc. However, there are concerns that the required application of pressure might be a source of variability. Ultrasound-based methods have been compared with modified Rodnan Skin Score in several studies, indicating acceptable construct validity. However, few studies have examined their criterion validity by providing comparisons to skin histology. Optical coherence-based methods show promising preliminary results for simultaneous assessment of skin fibrosis and vasculopathy. Further standardization and validation (including comparison to skin histology) of these promising novel assessment tools in large, longitudinal SSc cohort studies are needed to establish them as clinically useful outcome measures with acceptable sensitivity to change.

Recent advances in imaging techniques provide a promising opportunity for development of a valid and reliable assessment tool for quantification of SSc skin fibrosis, which can pave the way for approval of effective treatment options for this high burden disease manifestation.
In vitro bench testing using patient-specific 3D models for percutaneous pulmonary valve implantation with Venus P-valve
Authors: Han Yu , Shao Zehua , Sun Zirui , Han Yan , Xu Hongdang , Song Shubo , Pan Xiangbin , de Jaegere Peter P. T. , Fan Taibing , Zhang Gejun
Published: August 2023

Background:

Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve.

Methods:

Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University.

Results:

3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) (n = 2) or risk of compression coronary artery (n = 2). Concerning sizing, we found that an oversize of 2–5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P <0.001).

Conclusions:

In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique, as 2–5 mm sufficed.
Impact of Balloon Pulmonary Angioplasty on Right Ventricular Function in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Haner Wasserstein David , Frishman William H.
Published: August 2023

Chronic thromboembolic pulmonary hypertension (CTEPH) can develop in some patients after an acute pulmonary embolism. The disease is characterized by the conversion of emboli into fibrotic thrombi that chronically impede normal circulation through the pulmonary arteries and increase pulmonary vascular resistance. Over time, this increases right ventricular (RV) afterload and strains the RV. The RV compensates by undergoing cardiomyocyte hypertrophy and RV dilation that can maintain stroke volume. However, these adaptations eventually decrease cardiac output and lead to right heart failure. Balloon pulmonary angioplasty has been developed as a treatment option for CTEPH by systematically disrupting thrombosed vessels and improving blood flow throughout the pulmonary circulation. This ultimately reverses the structural maladaptation’s seen in CTEPH and improves RV function.
Sedentary behavior and risk of cardiovascular disease and all-cause mortality in United States adults with hypertension
Authors: Boudreaux Benjamin D. , Romero Emily K. , Diaz Keith M.
Published: August 2023

Background:

Growing evidence has implicated sedentary behavior is associated with cardiovascular and all-cause mortality, independent of moderate to vigorous physical activity (MVPA). Contrary to national physical activity guidelines, reductions in sedentary behavior are not promoted as a lifestyle modification in hypertensive adults. This may be in part because of a paucity of evidence demonstrating that sedentary behavior confers morbidity and mortality risk in hypertensive adults.

Purpose:

To examine the association between device-measured sedentary behavior and risk of cardiovascular and all-cause mortality and in hypertensive adults.

Methods:

Data for this analysis come from the 2003 to 2006 National Health and Nutrition Examination Survey, a nationally representative survey of US adults. Sedentary behavior and MVPA were assessed with an ActiGraph 7164 accelerometer. Hypertension was classified as blood pressure at least 140/≥90 mmHg or antihypertensive medication use.

Results:

Median follow-up was 14.5 years. After adjusting for covariates and MVPA, greater time spent in sedentary behavior was associated with an increased risk of cardiovascular mortality [quartile 1: REF, quartile 2: hazard ratio = 1.41 [95% confidence interval (95% CI) 0.83–2.38], quartile 3: hazard ratio = 1.25 (95% CI 0.81–1.94), quartile 4: hazard ratio = 2.14 (95% CI 1.41–3.24); P trend <0.001]. Greater sedentary behavior was also associated with an increased risk of all-cause mortality [quartile 1: REF: quartile 2: hazard ratio = 1.13 (95% CI 0.83–1.52), quartile 3: hazard ratio = 1.33 (95% CI 1.00–1.78), quartile 4: hazard ratio = 2.06 (95% CI 1.60, 2.64); P trend <0.001].

Conclusion:

Greater sedentary behavior is associated with increased risk of cardiovascular mortality and all-cause mortality among US adults with hypertension. These findings suggest reductions in sedentary behavior should be considered to reduce mortality risk in hypertensive adults.
Higher Heart Rate Is Independently Associated With Abnormal Body Mass Index in a J Shape Pattern
Authors: Hickcox Lucy , Bates Sharon , Hashemzadeh Mehrnoosh , Movahed Mohammad Reza
Published: August 2023

Background:

High heart rate (HR) is independently associated with higher cardiovascular mortality and usually occurs in sedentary persons. Inactivity can also lead to obesity. The purpose of this study was to evaluate the associations between body mass index as an independent marker of high HR.

Method:

Data generated from screening echocardiography, for the prevention of sudden death at the Anthony Bates Foundation, was used. Data from 1340 subjects, with documented HR and body mass index, between the ages 19–79 years with a mean age of 32 years, were studied. We correlated the presence of a high HR >90 beats per minute (bpm) with different body mass index (BMI) categories.

Results:

High HR was significantly associated with higher BMI categories and underweight subjects in adults suggesting a J shape association. A total of 22.7% of participants with an HR of more than 90 bpm had BMI >40 kg/m2, versus 19.0% of patients with BMI of 35–40 kg/m2 versus 13.5% of subjects with BMI of 30–35 kg/m2 versus 12.2% of subjects with BMI of 25–30 kg/m2–29.9 kg/m2, versus in 10.3% of subjects with BMI between 18.5 and 25 kg/m2, P < 0.01) Furthermore, increased HR was also more prevalent in underweight patient (17.4% in subjects with BMI < 18.5 kg/m2).

Conclusion:

High HR is strongly associated with obesity and underweight suggesting that maintaining a normal weight is associated with most positive effect on the cardiovascular system.
Cardiovascular Toxicity Associated With Immune Checkpoint Inhibitor Therapy: A Comprehensive Review
Authors: Chitsazan Mandana , Amin Ahmad , Ladel Luisa , Baig Alyza , Chitsazan Mitra
Published: August 2023

Immune checkpoint inhibitors (ICIs), a significant breakthrough treatment of cancer, exert their function through enhancing the immune system’s ability to recognize and attack cancer cells. However, these revolutionary cancer treatments have been associated with a range of immune-related adverse effects, including cardiovascular toxicity. The most commonly reported cardiovascular toxicities associated with ICIs are myocarditis, pericarditis, arrhythmias, and vasculitis. These cardiovascular manifestations are often severe and can lead to life-threatening complications. Therefore, prompt identification and management of these toxicities is critical, and a multidisciplinary teamwork by cardiologists and oncologists are required to ensure optimal patient outcomes. In this review, we summarize the current knowledge on the mechanisms underlying ICI-associated cardiovascular toxicity, clinical presentations of these toxicities, potential risk factors, diagnosis, management, and surveillance strategies during ICI therapy. While ICIs have already transformed cancer treatment, further research is needed to better understand and manage their immune-related cardiovascular effects, and possibly, to identify biomarkers which can predict the occurrence of these cardiovascular complications.
Corneal Morphological and Biomechanical Changes in Thyroid-Associated Ophthalmopathy
Authors: Zhang Te , Ye Huijing , Xiao Wei , Chen Rongxin , Huasheng Yang
Published: August 2023

Purpose:

This study aimed to evaluate corneal morphological and biomechanical changes in patients with thyroid-associated ophthalmopathy (TAO) and their correlations with activity and severity.

Methods:

Patients diagnosed with TAO were recruited and divided into groups by activity and severity. All subjects underwent a complete ophthalmic examination, including magnetic resonance imaging. Corneal topography was measured using a Pentacam device, and biomechanical parameters were obtained using a CorVis ST tonometer. Correlations among the corneal parameters, clinical activity score, and NOSPECS score were analyzed. Areas under the receiver operating characteristic curves were calculated to evaluate the diagnostic accuracy of corneal changes for active and severe TAO.

Results:

Fifty-three eyes with TAO and 16 healthy eyes were enrolled in our study. The back elevation, CorVis biomechanical index, tomographic and biomechanical index, stiffness parameter at the first applanation, deviation from normality in back elevation, relational thickness, and overall deviation from normality were significantly increased in patients with TAO (all P <0.05), whereas the smallest corneal thickness, maximum Ambrósio relational thickness, and deformation amplitude (DA) ratio were significantly decreased (all P <0.05). The clinical activity score was strongly positively correlated with back elevation (γ = 0.515, P <0.001). The NOSPECS score was strongly positively correlated with relational thickness and tomographic and biomechanical index (γ = 0.429 and 0.515, P <0.001) and negatively correlated with maximum Ambrósio relational thickness (γ = −0.53, P <0.001). Moreover, maximum Ambrósio relational thickness and the Ambrósio relational thickness through the horizontal meridian showed desirable diagnostic capacity in distinguishing mild TAO from moderate-severe TAO (areas under the receiver operating characteristic curve, 0.799 and 0.769).

Conclusions:

Corneal morphological and biomechanical changes were found in patients with TAO, which might be related to the presence of inflammation. Measurements of corneal morphological and biomechanical parameters could serve as references in evaluating TAO.