bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of extemporaneously prepared hydroxyurea solutions
Authors: Todd Hovey M , Patel Umesh S , Servos Mark A , Hovey Sara W , Van Haandel Leon
Published: July 2024

Purpose

To evaluate the stability of a new, more convenient (<30 minutes for preparation), extemporaneously prepared hydroxyurea solution over 78 days.

Methods

A high-performance liquid chromatography (HPLC) method using a hydrophilic interaction chromatography (HILIC) column was developed and validated to accurately measure the concentration of hydroxyurea directly from solution without the need for chemical derivatization. Hydroxyurea was dissolved in sterile water in less than 5 minutes to yield a 100-mg/mL solution, which was then diluted by an equal volume of ORA-sweet vehicle to yield a 50-mg/mL extemporaneously prepared solution of hydroxyurea. The solution samples were kept at refrigeration (4 °C), room temperature (26 °C), and elevated temperature (40 °C) for 78 days.

Results

The 50-mg/mL solutions of hydroxyurea in a 1:1 mixture of water and ORA-sweet kept at 4 °C and 26 °C showed no significant loss of potency (<2%) after 78 days. The solutions kept at 40 °C showed greater than 10% loss of potency after 28 days.

Conclusion

Extemporaneously compounded hydroxyurea 50-mg/mL solutions prepared in a 1:1 mixture of water and ORA-Sweet and stored in amber polypropylene plastic bottles were stable for at least 78 days at room temperature and under refrigeration.
Leaf functional trait evolution and its putative climatic drivers in African Coffea species
Authors: Hendrickx Aiden , Hatangi Yves , Honnay Olivier , Janssens Steven B , Stoffelen Piet , Vandelook Filip , Depecker Jonas
Published: July 2024

Background and Aims

Leaf traits are known to be strong predictors of plant performance and can be expected to (co)vary along environmental gradients. We investigated the variation, integration, environmental relationships and evolutionary history of leaf functional traits in the genus Coffea, typically a rainforest understorey shrub, across Africa. A better understanding of the adaptive processes involved in leaf trait evolution can inform the use and conservation of coffee genetic resources in a changing climate.

Methods

We used phylogenetic comparative methods to investigate the evolution of six leaf traits measured from herbarium specimens of 58 African Coffea species. We added environmental data and data on maximum plant height for each species to test trait–environment correlations in various (sub)clades, and we compared continuous trait evolution models to identify variables driving trait diversification.

Key Results

Substantial leaf trait variation was detected across the genus Coffea in Africa, which was mostly interspecific. Of these traits, stomatal size and stomatal density exhibited a clear trade-off. We observed low densities of large stomata in early-branching lineages and higher densities of smaller stomata in more recent taxa, which we hypothesize to be related to declining CO2 levels since the mid-Miocene. Brownian motion evolution was rejected in favor of white noise or Ornstein–Uhlenbeck models for all traits, implying these traits are adaptively significant rather than driven by pure drift. The evolution of leaf area was likely driven by precipitation, with smaller leaves in drier climates across the genus.

Conclusions

Generally, Coffea leaf traits appear to be evolutionarily labile and governed by stabilizing selection, though evolutionary patterns and correlations differ depending on the traits and clades considered. Our study highlights the importance of a phylogenetic perspective when studying trait relationships across related taxa, as well as the consideration of various taxonomic ranges.
Effectiveness of freezing temperatures on dormancy release of temperate woody species
Authors: Wang Huanjiong , Bai Wenrui , Hu Zhi , Lin Shaozhi , Ge Quansheng
Published: July 2024

Background and Aims

Spring phenological change of plants in response to global warming may affect many ecological processes and functions. Chilling temperature regulates budburst date by releasing dormancy. However, whether freezing temperatures (<0 °C) contribute to dormancy release remains of debate. Our poor understanding of the role of chilling makes estimating shifts in budburst date difficult.

Methods

A 2-year chilling–forcing experiment was explicitly designed to test the effects of chilling temperatures on dormancy release of nine temperate woody species in Beijing, China. A total of 1620 twigs were first exposed to a wide range of temperatures (−10 to 10 °C) with different durations and then moved to growth chambers. Based on budburst data in experimental conditions, we examined whether freezing temperatures are effective on dormancy release. We also developed a new framework for constructing chilling functions based on the curve between chilling duration and forcing requirement (FR) of budburst. The chilling function derived from this framework was not affected by experimental forcing conditions.

Key Results

We demonstrated that freezing temperatures down to −10 °C were effective in dormancy release. The rate of dormancy release, indicated by the rate of decay in the chilling duration–FR curve, did not differ significantly between chilling temperatures in most cases, although it exhibited a maximum value at 0 or 5 °C. The chilling function-associated phenological models could simulate budburst date from independent experimental and observational data with a mean RMSE of 7.07 d.

Conclusions

The effective freezing temperatures found here are contrary to the well-known assumption of <0 °C temperature generally not contributing to accumulated chilling in many previous chilling functions. A chilling function assuming that temperature below an upper temperature threshold has the same effects on dormancy release could be adopted to calculate chilling accumulation when using experiments to develop spring phenological models based on the chilling–forcing relationship.
Seasonal variation of vessel pits in sapwood: microscopical analyses of the morphology and chemical components of pit membrane encrustations in Fraxinus mandschurica
Authors: Yamagishi Shohei , Kojima Miho , Kuroda Katsushi , Abe Hisashi , Sano Yuzou
Published: July 2024

Background and Aims

Pit pairs and their filter-like partition, i.e. pit membranes, play important roles as water pathways, barriers and regulators in the water-conducting system of angiosperms. In Fraxinus species, the intervessel and vessel–parenchyma pit membranes in sapwood are normally encrusted during winter. Although these encrustations inevitably influence the performance of pits, their properties and functions remain unclear. This study aimed to reveal the morphological and chemical characteristics of encrustations in F. mandshurica in order to deepen understanding of the seasonal encrustation of pit membranes.

Methods

Seasonal and positional variations in the presence and morphology of encrustations were examined by field-emission scanning electron microscopy (FE-SEM). Cryo-FE-SEM for freeze-fixed greenwood samples was conducted to clarify whether encrustations were present in living trees. Chemical components were examined by histochemical staining using light and electron microscopy, immunofluorescence labelling and ultraviolet microspectroscopy.

Key Results

Encrustations began to deposit in autumn before leaf senescence and disappeared in spring before bud flushing. They infiltrated within the pit membranes, which suggested that they severely limit the permeation of pits. The encrustations differed in morphology among positions: they entirely filled the pit chambers in latewood, while they covered the pit membranes in earlywood. The encrustations were similarly observed in the samples that were freeze-fixed immediately after collection, indicating that they are present in living trees. The encrustations contained polysaccharides, including xyloglucan and homogalacturonan, and phenolic compounds, possibly including flavonoids and coumarins. These chemical components were also detected in droplets found in the latewood vessels with the encrustations, suggesting that the materials constituting encrustations were supplied through the vessel lumens.

Conclusions

Encrustations undoubtedly cover the pit membranes in living F. mandshurica trees in winter and their morphology and chemical composition indicate that they are impermeable, have positional differences in function and are characterized by elaborate deposition/removal processes.
Delineation of the impacts of varying 6-benzylaminopurine concentrations on physiological, biochemical and genetic traits of different olive cultivars under in vitro conditions
Authors: Zhao Ting , Khatoon Sadia , Matloob Javed Muhammad , Ghazy Abdel-Halim , Al-Doss Abdullah A , Rauf Muhammad , Khalid Taimoor , Ding Chuanbo , Shah Zahid Hussain
Published: July 2024

Abstract. The plant growth regulator 6-benzylaminopurine (BAP) is an important component of plant nutrient medium with tendency to accelerate physiological, biochemical and molecular processes in woody plants such as olive. To date, limited knowledge is available on the role of BAP in mediating physiological, biochemical and genetic activities in olives under in vitro conditions. To cover this research gap, the current study was conducted with the objective of studying the role of BAP in regulating physiological traits (chlorophyll, CO2 assimilation), antioxidant enzymes (superoxide dismutase, catalase and peroxidase), metabolic contents (starch, sucrose and flavonoids) and gene expression (OeRbcl, OePOD10, OeSOD10, OeCAT7, OeSS4, OeSuSY7, OeF3GT and OeChlH) under varying concentrations (0, 0.5, 1.5 and 2.5 mg L−1) within the provided in vitro conditions. The explants obtained from different olive cultivars (‘Leccino’, ‘Gemlik’, ‘Moraiolo’, ‘Arbosana’) were cultured on olive medium (OM) provided with different BAP concentrations using a two-factorial design, and data were analysed statistically. All traits increased significantly under in vitro conditions due to increasing concentrations of BAP; however, this increase was more dramatic at 2.5 mg L−1 and the least dramatic at 0.5 mg L−1. Moreover, correlation, principal component analysis and heatmap cluster analysis confirmed significant changes in the paired association and expression of traits with changing BAP concentration and type of olive cultivars. Likewise, the expression of all genes varied due to changes in BAP concentration in all cultivars, corresponding to variations in physiological and biochemical traits. Moreover, the spectrographs generated via scanning electron microscopy further indicated the variations in the distribution of elements in olive leaf samples due to varying BAP concentrations. Although all cultivars showed a significant response to in vitro varying concentrations of BAP, the response of Arbosana was statistically more significant. In conclusion, the current study proved the dynamic impact of the varying BAP concentrations on regulating the physiological, biochemical, and molecular attributes of olive cultivars.
Pearls of Wisdom: Expert Insights for Communicating With Aesthetic Patients
Authors: Martin Serena , Nugent Nora , Pacifico Marc D
Published: July 2024

Good communication with patients is essential in aesthetic surgery. In particular, the challenge of expectation management is crucial to optimizing patient satisfaction, which may be irrespective of objective outcomes. Experienced plastic surgeons inevitably refine their consultation process and hone their communication skills throughout years of practice. The invaluable “pearls” that expert surgeons develop would be beneficial to all surgeons, and particularly to those early in their practice. This prompted the authors to explore whether the communication skills acquired by a selected group of highly regarded plastic surgeons could be condensed and categorized in a way from which others could benefit. We seek to demonstrate that there are a select number of core messages that many plastic surgeons desire to communicate, particularly during the preoperative consultation process. Various phrases and aphorisms have been formulated within these subtopics that we hope will be positively incorporated into colleagues’ practices to improve the patient experience, and ultimately patients’ understanding of and satisfaction with their outcomes.
Genotype imputation in F2 crosses of inbred lines
Authors: Pierotti Saul , Welz Bettina , Osuna-López Mireia , Fitzgerald Tomas , Wittbrodt Joachim , Birney Ewan
Published: July 2024

Motivation

Crosses among inbred lines are a fundamental tool for the discovery of genetic loci associated with phenotypes of interest. In organisms for which large reference panels or SNP chips are not available, imputation from low-pass whole-genome sequencing is an effective method for obtaining genotype data from a large number of individuals. To date, a structured analysis of the conditions required for optimal genotype imputation has not been performed.

Results

We report a systematic exploration of the effect of several design variables on imputation performance in F2 crosses of inbred medaka lines using the imputation software STITCH. We determined that, depending on the number of samples, imputation performance reaches a plateau when increasing the per-sample sequencing coverage. We also systematically explored the trade-offs between cost, imputation accuracy, and sample numbers. We developed a computational pipeline to streamline the process, enabling other researchers to perform a similar cost–benefit analysis on their population of interest.

Availability and implementation

The source code for the pipeline is available at https://github.com/birneylab/stitchimpute. While our pipeline has been developed and tested for an F2 population, the software can also be used to analyse populations with a different structure.
Representing core gene expression activity relationships using the latent structure implicit in Bayesian networks
Authors: Gao Jiahao , Gerstein Mark
Published: July 2024

Motivation

Many types of networks, such as co-expression or ChIP-seq-based gene-regulatory networks, provide useful information for biomedical studies. However, they are often too full of connections and difficult to interpret, forming “indecipherable hairballs.”

Results

To address this issue, we propose that a Bayesian network can summarize the core relationships between gene expression activities. This network, which we call the LatentDAG, is substantially simpler than conventional co-expression network and ChIP-seq networks (by two orders of magnitude). It provides clearer clusters, without extraneous cross-cluster connections, and clear separators between modules. Moreover, one can find a number of clear examples showing how it bridges the connection between steps in the transcriptional regulatory network and other networks (e.g. RNA-binding protein). In conjunction with a graph neural network, the LatentDAG works better than other biological networks in a variety of tasks, including prediction of gene conservation and clustering genes.

Availability and implementation

Code is available at https://github.com/gersteinlab/LatentDAG
MetaHD: a multivariate meta-analysis model for metabolomics data
Authors: Liyanage Jayamini C , Prendergast Luke , Staudte Robert , De Livera Alysha M
Published: July 2024

Motivation

Meta-analysis methods widely used for combining metabolomics data do not account for correlation between metabolites or missing values. Within- and between-study variability are also often overlooked. These can give results with inferior statistical properties, leading to misidentification of biomarkers.

Results

We propose a multivariate meta-analysis model for high-dimensional metabolomics data (MetaHD), which accommodates the correlation between metabolites, within- and between-study variances, and missing values. MetaHD can be used for integrating and collectively analysing individual-level metabolomics data generated from multiple studies as well as for combining summary estimates. We show that MetaHD leads to lower root mean square error compared to the existing approaches. Furthermore, we demonstrate that MetaHD, which exploits the borrowing strength between metabolites, could be particularly useful in the presence of missing data compared with univariate meta-analysis methods, which can return biased estimates in the presence of data missing at random.

Availability and implementation

The MetaHD R package can be downloaded through Comprehensive R Archive Network (CRAN) repository. A detailed vignette with example datasets and code to prepare data and analyses are available on https://bookdown.org/a2delivera/MetaHD/.
TSpred: a robust prediction framework for TCR–epitope interactions using paired chain TCR sequence data
Authors: Kim Ha Young , Kim Sungsik , Park Woong-Yang , Kim Dongsup
Published: July 2024

Motivation

Prediction of T-cell receptor (TCR)–epitope interactions is important for many applications in biomedical research, such as cancer immunotherapy and vaccine design. The prediction of TCR–epitope interactions remains challenging especially for novel epitopes, due to the scarcity of available data.

Results

We propose TSpred, a new deep learning approach for the pan-specific prediction of TCR binding specificity based on paired chain TCR data. We develop a robust model that generalizes well to unseen epitopes by combining the predictive power of CNN and the attention mechanism. In particular, we design a reciprocal attention mechanism which focuses on extracting the patterns underlying TCR–epitope interactions. Upon a comprehensive evaluation of our model, we find that TSpred achieves state-of-the-art performances in both seen and unseen epitope specificity prediction tasks. Also, compared to other predictors, TSpred is more robust to bias related to peptide imbalance in the dataset. In addition, the reciprocal attention component of our model allows for model interpretability by capturing structurally important binding regions. Results indicate that TSpred is a robust and reliable method for the task of TCR–epitope binding prediction.

Availability and implementation

Source code is available at https://github.com/ha01994/TSpred.
Contrasting interspecific hybridization patterns in two goby groups radiating in divergent freshwater habitats
Authors: Ito Ryosuke K , Mishina Tappei , Hashiguchi Yasuyuki , Watanabe Katsutoshi
Published: July 2024

Hybridization and introgression between closely related species significantly affect their evolutionary and ecological processes. Understanding the ecological, environmental, and geographical conditions that promote their occurrence is imperative. It is hypothesized that species inhabiting geologically unstable habitats or with life-history constraints that prevent evasion from such environments are more prone to interspecific hybridization, due to limited development of prezygotic isolation. To test this hypothesis, we conducted a comparative analysis of genome-wide hybridization patterns in two freshwater goby groups of Gymnogobius: the castaneus- and urotaenia-groups. Utilizing the newly determined draft genome of G. isaza and single nucleotide variants identified by RNA sequencing, we first established the species phylogeny and then examined genetic signatures of interspecific hybridization in each group. The results revealed that all castaneus-group species, which primarily inhabit unstable habitats such as ponds, have undergone interspecific hybridization. Conversely, no species of the urotaenia-group showed clear evidence of hybridization over a period of more than 1 million years. These species inhabit an ancient lake (one species) or rivers (three amphidromous species), the latter possessing potential dispersal abilities in early life to evade geological disturbances. These ecology–geology relationships have remarkable implications for the intricate processes of adaptation and speciation.
Writing as Social Work: Thematic Review of the Literature
Authors: Rai Lucy , Ferguson Gillian , Giddings Lindsay
Published: July 2024

This article offers a thematic review of research and analysis of academic and practice-based social work writing. It aims to highlight specific challenges, arguing that support is needed in the development of writing as a core element of professional practice. Social work writing in the United Kingdom has been framed as a ‘problematic’, time-intensive activity [Lillis, T. (2023) ‘Professional written voice “in flux”: The case of social work’, Applied Linguistics Review, 14(3), pp. 615–41]. It records practice, but is also a vital tool for undertaking assessments, formulating professional judgements, decision making and multi-agency collaboration. However, the centrality of writing to social work practice is not reflected in the regulatory frameworks for the profession in the United Kingdom where it only appears in the context of ‘report writing’ and loosely ‘communication’. The discussion is contextualised within a theoretical framing of social work writing followed by a discussion of student writing and then writing in professional practice. The article addresses the themes related to academic writing of concerns about the quality of writing; disciplinarity; conventions and implicit codes; and challenges to teach professional writing. In relation to practice-based writing, the article addresses the themes of social work as a ‘writing intensive’ profession; writing as enacting practice; and the challenges and experience of social work writers.
Faster than expected: 5-year re-surveys reveal accelerating plant colonization in two proglacial forelands of the Gran Paradiso National Park (NW Italian Alps)
Authors: Nota Ginevra , Ravetto Enri Simone , Lonati Michele , Mainetti Andrea
Published: July 2024

Proglacial vegetation communities are facing major challenges today due to fast glacier retreat and global warming, resulting in possible changes in plant colonization patterns. By re-surveying permanent plots along two alpine chronosequences (encompassing 5 to 165 years from deglaciation) with a 5-year time span, we aimed to (i) assess short-term vegetation changes and (ii) compare current vegetation trajectories with those predicted by the chronosequence approach. We analysed the number and cover of total, pioneer, and alpine grassland species and calculated the slopes of the trajectories of the chronosequence and observed on permanent plots. As expected, the number and cover of total, pioneer, and grassland species increased during the 5 years of the study. Moreover, we observed a significant acceleration in plant colonization (21 and 45 times faster increase in species richness and cover, respectively) compared to the chronosequence predictions. These dramatic changes in vegetation dynamics of proglacial plant communities were probably induced by the increased temperatures and longer growing seasons occurring in the Alps.
Prenatal assessment of brain malformations on neuroimaging: an expert panel review
Authors: Pogledic Ivana , Mankad Kshitij , Severino Mariasavina , Lerman-Sagie Tally , Jakab Andras , Hadi Efrat , Jansen Anna C , Bahi-Buisson Nadia , Di Donato Natalya , Oegema Renske , Mitter Christian , Capo Ivan , Whitehead Matthew T , Haldipur Parthiv , Mancini Grazia , Huisman Thierry A G M , Righini Andrea , Dobyns Bill , Barkovich James A , Milosevic Natasa Jovanov , Kasprian Gregor , Lequin Maarten
Published: July 2024

Brain malformations represent a heterogeneous group of abnormalities of neural morphogenesis, often associated with aberrations of neuronal connectivity and brain volume. Prenatal detection of brain malformations requires a clear understanding of embryology and developmental morphology through the various stages of gestation.

This expert panel review is written with the central aim of providing an easy-to-understand road map to improve prenatal detection and characterization of structural malformations based on the current understanding of normal and aberrant brain development. For every developmental stage, the utility of each available neuroimaging modality, including prenatal multiplanar neuro sonography, anatomical MRI and advanced MRI techniques, as well as further insights from post-mortem imaging, has been highlighted.
Inhibition of PHLDA3 expression in human superoxide dismutase 1-mutant amyotrophic lateral sclerosis astrocytes protects against neurotoxicity
Authors: Szebényi Kornélia , Vargová Ingrid , Petrova Veselina , Turečková Jana , Gibbons George M , Řehořová Monika , Abdelgawad Mai , Sándor Alexandra , Marekova Dana , Kwok Jessica C F , Jendelová Pavla , Fawcett James W , Lakatos András
Published: July 2024

Pleckstrin homology-like domain family A—member 3 (PHLDA3) has recently been identified as a player in adaptive and maladaptive cellular stress pathways. The outcome of pleckstrin homology-like domain family A—member 3 signalling was shown to vary across different cell types and states. It emerges that its expression and protein level are highly increased in amyotrophic lateral sclerosis (ALS) patient-derived astrocytes. Whether it orchestrates a supportive or detrimental function remains unexplored in the context of neurodegenerative pathologies. To directly address the role of pleckstrin homology-like domain family A—member 3 in healthy and ALS astrocytes, we used overexpression and knockdown strategies. We generated cultures of primary mouse astrocytes and also human astrocytes from control and ALS patient-derived induced pluripotent stem cells harbouring the superoxide dismutase 1 mutation. Then, we assessed astrocyte viability and the impact of their secretome on oxidative stress responses in human stem cell-derived cortical and spinal neuronal cultures. Here, we show that PHLDA3 overexpression or knockdown in control astrocytes does not significantly affect astrocyte viability or reactive oxygen species production. However, PHLDA3 knockdown in ALS astrocytes diminishes reactive oxygen species concentrations in their supernatants, indicating that pleckstrin homology-like domain family A—member 3 can facilitate stress responses in cells with altered homeostasis. In support, supernatants of PHLDA3-silenced ALS and even control spinal astrocytes with a lower pleckstrin homology-like domain family A—member 3 protein content could prevent sodium arsenite-induced stress granule formation in spinal neurons. Our findings provide evidence that reducing pleckstrin homology-like domain family A—member 3 levels may transform astrocytes into a more neurosupportive state relevant to targeting non-cell autonomous ALS pathology.
Early protein delivery in critically ill patients with acute kidney injury: post hoc analysis of a multicenter cluster-randomized controlled trial
Authors: Lv Cheng , Zhou Lingliang , Zhou Yufeng , Lew Charles Chin Han , Lee Zheng-Yii , Hasan M Shahnaz , Li Baiqiang , Liu Yang , Lin Jiajia , Mao Wenjian , Stoppe Christian , van Zanten Arthur Raymond Hubert , Li Weiqin , Liu Yuxiu , Ke Lu ,   the Chinese Critical Care Nutrition Trials Group (CCCNTG), Lv Cheng , Zhou Lingliang , Zhou Yufeng , Lew Charles Chin Han , Lee Zheng-Yii , Hasan M Shahnaz , Li Baiqiang , Liu Yang , Lin Jiajia , Mao Wenjian , Stoppe Christian , Hubert van Zanten Arthur Raymond , Li Weiqin , Liu Yuxiu , Ke Lu
Published: July 2024

Background

There is controversy over the optimal early protein delivery in critically ill patients with acute kidney injury (AKI). This study aims to evaluate whether the association between early protein delivery and 28-day mortality was impacted by the presence of AKI in critically ill patients.

Methods

This is a post hoc analysis of data from a multicenter cluster-randomised controlled trial enrolling newly admitted critically ill patients (n = 2772). Participants without chronic kidney disease and with complete data concerning baseline renal function were included in this study. The primary outcome was 28-day mortality. Cox proportional hazards models were used to analyze the association between early protein delivery, reflected by mean protein delivery from day 3–5 after enrollment, 28-day mortality and whether baseline AKI stages interacted with this association.

Results

Overall, 2552 patients were included, among whom 567 (22.2%) had AKI at enrollment (111 stage I, 87 stage II, 369 stage III). Mean early protein delivery was 0.60 ± 0.38 g/kg/day among the study patients. In the overall study cohort, each 0.1 g/kg/day increase in protein delivery was associated with a 5% reduction in 28-day mortality[hazard ratio (HR) = 0.95; 95% confidence interval (CI) 0.92–0.98, p < 0.001]. The association between early protein delivery and 28-day mortality significantly interacted with baseline AKI stages (adjusted interaction p = 0.028). Each 0.1 g/kg/day increase in early protein delivery was associated with a 4% reduction in 28-day mortality (HR = 0.96; 95%CI 0.92–0.99, p = 0.011) among patients without AKI and 9% (HR = 0.91; 95%CI 0.84–0.99, p = 0.021) among those with AKI stage III. However, such associations cannot be observed among patients with AKI stages I and II.

Conclusions

Increased early protein delivery (up to close to the guideline recommendation) was associated with reduced 28-day mortality in critically ill patients without AKI and with AKI stage III, but not in those with AKI stage I or II.
EIF2S2 transcriptionally upregulates HIF1α to promote gastric cancer progression via activating PI3K/AKT/mTOR pathway
Authors: Wang Zhiyong , Zhang Yingyi , Xue Yingwei , Huang Wei , Zhang Hongfeng
Published: July 2024

Eukaryotic translation initiation factor 2 subunit beta (EIF2S2) is a protein that controls protein synthesis under various stress conditions and is abnormally expressed in several cancers. However, there is limited insight regarding the expression and molecular role of EIF2S2 in gastric cancer. In this study, we identified the overexpression of EIF2S2 in gastric cancer by immunohistochemical staining and found a positive correlation between EIF2S2 expression and shorter overall survival and disease-free survival. Functionally, we revealed that EIF2S2 knockdown suppressed gastric cancer cell proliferation and migration, induced cell apoptosis, and caused G2 phase cell arrest. Additionally, EIF2S2 is essential for in vivo tumor formation. Mechanistically, we demonstrated that EIF2S2 transcriptionally regulated hypoxia-inducible factor-1 alpha (HIF1α) expression by NRF1. The promoting role of EIF2S2 in malignant behaviors of gastric cancer cells depended on HIF1α expression. Furthermore, the PI3K/AKT/mTOR signaling was activated upon EIF2S2 overexpression in gastric cancer. Collectively, EIF2S2 exacerbates gastric cancer progression via targeting HIF1α, providing a fundamental basis for considering EIF2S2 as a potential therapeutic target for gastric cancer patients.
Stem cells, Notch-1 signaling, and oxidative stress: a hellish trio in cancer development and progression within the airways. Is there a role for natural compounds?
Authors: Chiappara Giuseppina , Di Vincenzo Serena , Cascio Caterina , Pace Elisabetta
Published: July 2024

Notch-1 signaling plays a crucial role in stem cell maintenance and in repair mechanisms in various mucosal surfaces, including airway mucosa. Persistent injury can induce an aberrant activation of Notch-1 signaling in stem cells leading to an increased risk of cancer initiation and progression. Chronic inflammatory respiratory disorders, including chronic obstructive pulmonary disease (COPD) is associated with both overactivation of Notch-1 signaling and increased lung cancer risk. Increased oxidative stress, also due to cigarette smoke, can further contribute to promote cancer initiation and progression by amplifying inflammatory responses, by activating the Notch-1 signaling, and by blocking regulatory mechanisms that inhibit the growth capacity of stem cells. This review offers a comprehensive overview of the effects of aberrant Notch-1 signaling activation in stem cells and of increased oxidative stress in lung cancer. The putative role of natural compounds with antioxidant properties is also described.
Exhausted Lag-3+ CD4+ T cells are increased in pediatric Inflammatory Bowel Disease
Authors: Schnell Alexander , Aicher Carmen , Schnegelsberg Philipp A , Schwarz Benedikt , Schmidt Hannah , Allabauer Ida , Rueckel Aline , Regensburger Adrian P , Woelfle Joachim , Hoerning André
Published: July 2024

T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. Twenty-one responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4β7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17-shifted phenotype. The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.
The characteristic pattern of functional connectivity density influenced by postmenopausal females in the preclinical stage of dementia
Authors: Huang Jingjing , Zhou Hang , Xiao Zhendong , Xu Xiuyun , Zhou Huaijun ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: July 2024

Subjective cognitive decline (SCD) is considered an early indicator of Alzheimer’s disease. Previous evidence suggests that postmenopausal females are at heightened risk for developing dementia. However, the potential effects of gender (i.e. postmenopausal female) on functional connectivity density (FCD) in individuals with SCD are not well understood. A total of 56 healthy controls and 57 subjects with SCD were included. The short-range and long-range FCD (srFCD and lrFCD) mapping of each participant was calculated. The interactive effect of gender × diagnosis on the FCD was explored by two-way analysis of variance. The interaction effect of gender × diagnosis on lrFCD was primarily in the right middle frontal gyrus (MFG). The older males with SCD exhibited significantly enhanced lrFCD in the right MFG relative to other subgroups. The lrFCD of the right MFG was positively associated with cognitive performance in older females with SCD. Cognition-related functional terms were significantly related to the right MFG. Decreased lrFCD of the right MFG in cognitively normal older women may explain why postmenopausal females have a higher risk for progression to dementia than men. Furthermore, this altered pattern could be applied to identify individuals with a high risk for dementia.
Oral stimulation with glucose and fructose, but not sucrose, accelerates gastric emptying in humans
Authors: Kanda Masako , Kashima Hideaki , Miura Akira , Fukuba Yoshiyuki , Takahashi Makoto , Yamaoka Endo Masako
Published: July 2024

Postprandial regulation of the gastric emptying (GE) rate plays an important role in food intake. Although oral sweetening with glucose may accelerate GE, the effects of different sweetness intensities of glucose (10% and 20%, w/v) and other energy sweeteners (e.g. fructose and sucrose) remain uncertain. The purpose of this study was to determine the effects of different glucose concentrations (Experiment 1) and different sugars with the same sweet taste intensity (Experiment 2) on postprandial GE. In both experiments, after ingesting a 200 kcal carbohydrate solution containing 50 g of maltodextrin, participants repeatedly sipped, but did not swallow, one of three (water, 10% and 20%, w/v glucose) or four (water and equally sweet 20%, w/v glucose, 12%, w/v fructose, and 14%, w/v sucrose) solutions for 1 min every 5 min over a 30 min period. GE was evaluated by measuring the temporal change in the cross-sectional area of the gastric antrum using ultrasound. In Experiment 1, oral stimulation with 20% (w/v) glucose resulted in greater GE than the control stimulus (i.e. water), but the effect of stimulation with 10% (w/v) glucose on GE was not different from that of the control stimulus. In Experiment 2, stimulation with 20% (w/v) glucose or 12% (w/v) fructose resulted in greater GE than the control stimulus. However, the effect of stimulation with 14% (w/v) sucrose on GE did not differ from that of the control stimulus. Consequently, oral stimulation with glucose or fructose solutions of moderate to high sweetness following a meal facilitates postprandial GE.
PANGEN: an online platform for the comparison and creation of diagnostic gene panels
Authors: Isakov Ofer , Marek-Yagel Dina , Greenberg Rotem , Naftali Michal , Ben-Shachar Shay
Published: July 2024

Targeted gene panel sequencing is used to limit the search for causative genetic variants solely to genes with an established association with the phenotype. The design of gene panels is challenging due to the lack of consensus regarding phenotypic associations for some genes, which results in high variation in gene composition for the same panel offered by different laboratories. We developed PANGEN, a platform that provides a centralized resource for gene panel information, with the ability to compare and generate new intelligent diagnostic panels. Gene–phenotype associations were collected from 12 public and commercial sources (Blueprint, Cegat, Centogene, ClinGen, Fulgent, GeneDx, Health in Code, Human Phenotype Ontology, Invitae, PanelApp, Prevention genetics, and Pronto diagnostics). Gene–phenotype associations are categorized into tiers according to categories derived from the original source panel. Pairwise panel similarity was calculated by dividing the number of common genes by the total number of genes in both panels. Regions with extreme guanine-cytosine (GC) content were collected from the Genome in a Bottle stratifications dataset, and putative genomic duplications were retrieved from the University of Santa Cruz database. Overall, 1533 panels, 9759 phenotypes, and 6979 genes were collected. The platform provides an interface to (i) explore and compare collected panels, (ii) find similar panels, (iii) identify genes with high GC content or duplication levels, (iv) generate gene panels by combining panels from various sources, and (v) stratify a generated panel into genes with a strong phenotype association (‘core’) and those with a weaker association (‘extended’). The presented platform represents a unique resource for gene panel exploration and comparison that facilitates the generation of tailored diagnostic panels through a public online web server.

Database URL: https://c-gc.shinyapps.io/PANGEN/
Preventable Predictive Factors of Post-colonoscopy Colorectal Cancer in Inflammatory Bowel Disease
Authors: De Cristofaro Elena , Marafini Irene , Mancone Roberto , Fiorillo Mariasofia , Franchin Martina , Mattogno Adelaide , Neri Benedetto , Zorzi Francesca , Del Vecchio Blanco Giovanna , Biancone Livia , Calabrese Emma , Giannarelli Diana , Monteleone Giovanni
Published: July 2024

Background and Aim

Post-colonoscopy colorectal cancer [PCCRC] is a colorectal cancer [CRC] diagnosed after a colonoscopy in which no cancer was detected [index colonoscopy]. Although the overall cumulative rates of PCCRC are low in both the general population and inflammatory bowel disease [IBD] patients, the overall incidence of PCCRC in IBD is greater than that documented in the general population. This study aimed to identify the index colonoscopy-related factors and patients’ characteristics influencing IBD-associated PCCRC development.

Methods

We carried out an observational, retrospective study in which IBD-associated PCCRCs were diagnosed between 2010 and 2023. The PCCRC group was compared with a control cohort of IBD patients without CRC, matched 1:1 by several demographic and clinical features as well as characteristics of index colonoscopy, to minimise selection bias.

Results

Among 61 CRCs identified, 37 [61%] were PCCRC. Twelve of the 37 [32%] PCCRC were diagnosed within 12 months after the previous negative colonoscopy, 15 [41%] within 12–36 months, and 10 [27%] within 36–60 months. In the multivariate analysis, the inadequate bowel preparation of the index colonoscopy (odds ratio [OR]: 5.9; 95% confidence interval [CI]: 11.1-31.4) and the presence of high-risk factors for CRC [OR: 24.03; 95% CI: 3.1-187.8] were independently associated with PCCRC. Conversely, prior exposure to immunosuppressors or biologics [OR: 0.17; 95% CI: 0.03-0.83] and random biopsies sampling at index colonoscopy [OR: 0.19; 95% CI: 0.04-0.85] were inversely associated with PCCRC.

Conclusions

More than 50% of CRCs in our population were PCCRC. PCCRCs were associated with previous inadequate cleansing and occurred more frequently in high-risk patients.
Evidence for an adult summer diapause in mountain pine beetle (Coleoptera: Curculionidae) that varies geographically and among haplogroups
Authors: Hansen E Matthew , Bentz Barbara J , Baggett L Scott
Published: July 2024

Identifying dormancy traits is important for predicting insect population success, particularly in a changing climate that could disrupt evolved traits. The mountain pine beetle (Dendroctonus ponderosae Hopkins) is native to North America, is responsible for millions of acres of tree mortality, and is expanding northward in Canada. Research has identified thermal traits important to epidemic-phase ecology that vary among populations. Genomic research identified 3 mountain pine beetle haplogroups representing Pleistocene glacial refugia. Significant variation in generation timing aligning with the haplogroups has been observed. The adult stage was previously identified as the likely cause of differences among populations, although the mechanism(s) remain unclear. We tested for an adult summer diapause that varies among populations from 2 haplogroups, southern Colorado (CO) (central haplogroup) and southern Idaho (ID) (eastern haplogroup) using respirometry and reproduction experiments. Warm temperatures (25 °C) resulted in reduced respiration rates of central haplogroup mountain pine beetle compared to a cool temperature treatment (15 °C), whereas respiration of the eastern haplogroup did not differ between the treatments. Mated pairs of central haplogroup mountain pine beetle reared/held at 15 °C were more likely to be classified with a higher reproductive success rating compared to pairs reared/held at 25 °C. These results support a facultative summer adult diapause in southern CO central haplogroup mountain pine beetle. Manifestation of this diapause was low/absent among adults from the northerly ID location. This diapause likely serves to maintain univoltinism shown to be important for mountain pine beetle epidemic-phase ecology. The variation occurring among haplogroups highlights the long-term, evolved processes driving local adaptations in mountain pine beetle.
Ventricular fibrillation during football training as a consequence of kratom and caffeine use in an adolescent: case report
Authors: Dodulík Jozef , Plášek Jiří , Handlos Petr , Gřegořová Andrea , Václavík Jan
Published: July 2024

Background

There is an increase in the sale of legal drugs in our country. One of these substances is kratom. Kratom (Mitragyna speciosa) is a partial agonist of the opioid kappa, mu, and delta receptors. It acts as a stimulant at low concentrations, making users feel more energetic and euphoric. It has sedative and antinociceptive effects at higher doses.

Case summary

An 18-year-old man collapsed during football training and required cardiopulmonary resuscitation; the initial rhythm was ventricular fibrillation managed by defibrillation. Laboratory parameters were unremarkable. Blood samples sent for toxicological evaluation were positive for kratom and caffeine. Echocardiographic examination, coronary computed tomography angiography, and cardiac magnetic resonance imaging did not prove the cause. Genetic testing did not find a pathogenic gene variant associated with familial ventricular fibrillation, but a variant of unknown significance was found in MYOM1. Given this situation, we implanted an implantable cardioverter-defibrillator (ICD) from the secondary prevention of sudden cardiac death (SCD) according to the guidelines of the European Society of Cardiology (ESC). No recurrence of ventricular arrhythmia has been reported by ambulatory ICD memory checks on our patient.

Discussion

In some country, kratom is freely available and sold as a plant, not a drug. Only incident cases of ventricular fibrillation after kratom use are described in the literature. There is insufficient scientific evidence linking kratom to ventricular fibrillation. This is an absolutely crucial case report of this type, which has not yet been published in similar circumstances in the world. Therefore, the development of ventricular fibrillation was assumed to be due to a combination of kratom, caffeine, and exercise. The safety profile and effects of kratom should be the subject of future research. We would like to stress the importance of reporting further case series for more scientific evidence and thus increasing the pressure for stricter availability and regulation of kratom in some countries, especially where it is over-the-counter.
First application of the distal radial approach for severe mechanical surgical aortic valve paravalvular leak transcatheter closure with a double vascular plug: a case report
Authors: Sasi Viktor , Fontos Géza , Kormányos Árpád , Vértesaljai Márton , Ruzsa Zoltán
Published: July 2024

Background

Severe aortic paravalvular leaks (PVLs) after surgical mechanical aortic valve replacement (AVR) represent a high risk for congestive heart failure, haemolysis, and infective endocarditis. This is the first reported case of distal radial artery (DRA) access for severe mechanical aortic PVL closure with a sequential double vascular plug guided by computed tomography angiography (CTA), transoesophageal echocardiography (TOE), and 3D TOE in an acute setting.

Case summary

A 51-year-old male presented with significant mixed aortic valve disease. Aortic valve replacement was performed (Slimline Bicarbon A-25 mm) according to guidelines. Four and 16 days later, a re-exploration was carried out due to pericardial effusion. Four months after discharge from rehabilitation, the patient was readmitted due to worsening dyspnoea on exertion and then at rest. Transthoracic echocardiography, TOE, and consequently, CTA, revealed severe PVL, following which the procedure of transcatheter PVL closure was chosen, with a preference for DRA access. After a CTA scan analysis and angiographic, TOE, and 3D TOE visualization of the leak, a 14/5 mm and a 10/5 mm vascular plug (AVPIII) were deployed to achieve good results. A 9-month clinical, echocardiographic, and CTA follow-up revealed good long-term results.

Discussion

For transcatheter PVL closure, CTA is helpful for not only vascular access planning, but also a visualization of the magnitude of the leak, location, and device planning. This case report demonstrates that the distal radial approach is feasible in patients with severe mechanical aortic valve PVL retrograde transcatheter closure. DRA access could possibly represent less bleeding and vascular access site complications when compared with femoral access and has some potential advantages over regular radial access.