bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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 &lt; 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract
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.