bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing inhaled corticosteroid use in patients with chronic obstructive pulmonary disease: assessing blood eosinophils, neutrophil–to–lymphocyte ratio, and mortality outcomes in US adults
Authors: Hu Han-Shuo , Wang Zhuo , Jian Ling-Yan , Zhao Li-Mei , Liu Xiao-Dong
Published: November 2023

Objective

Accurate biomarkers for evaluating mortality rates in patients with chronic obstructive pulmonary disease (COPD) remain scarce. This study aimed to explore the relationships between mortality rates in patients with COPD and blood eosinophil counts, neutrophil counts, and lymphocyte counts, along with the neutrophil–to–lymphocyte ratio (NLR). Additionally, we sought to identify the optimal response values for these biomarkers when utilizing inhaled corticosteroids (ICS).

Methods

Utilizing a nationally representative, multistage cross–sectional design and mortality correlation study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 involving US adults aged 40 years or older with COPD. The primary endpoint was all–cause mortality, with Kaplan–Meier survival curves and restricted cubic splines applied to illustrate the relationship between leukocyte–based inflammatory markers and mortality. The analysis was conducted in 2023.

Results

Our analysis included 1,715 COPD participants, representing 6,976,232 non–institutionalized US residents [weighted mean age (SE), 62.09 (0.28) years; range, 40–85 years]. Among the participants, men constituted 50.8% of the population, and the weighted mean follow–up duration was 84.9 months. In the ICS use group, the weighted proportion of participants over 70 years old was significantly higher compared with the non–ICS use group (31.39% vs 25.52%, p < 0.0001). The adjusted hazard ratios for all–cause mortality related to neutrophil counts, lymphocyte counts, and NLR were 1.10 [95% confidence interval (CI), 1.04–1.16, p < 0.001], 0.83 (95% CI, 0.71–0.98; p = 0.03), and 1.10 (95% CI, 1.05–1.15; p < 0.0001), respectively. Optimal ICS response was linked with higher levels of eosinophil count (≥240 cells/μL), neutrophil count (≥3,800 cells/μL), NLR (≥4.79), and lower levels of lymphocyte count (<2,400 cells/μL).

Conclusion

Adjusted baseline neutrophil, lymphocyte counts, and NLR serve as independent risk factors for all–cause mortality in patients with COPD. Further, ICS application appears to mitigate mortality risk, particularly when NLR levels reach 4.79 or higher, underlining the importance of ICS in COPD management.

Graphical abstract

Inhaled Corticosteroid Use in COPD: A Comparative Analysis of Leukocyte-based Inflammatory Markers and Mortality Outcomes Based on NHANES Data (1999-2018).
Arachidonate 15-lipoxygenase-mediated production of Resolvin D5n-3 DPA abrogates pancreatic stellate cell-induced cancer cell invasion
Authors: Aguirre Gabriel A. , Goulart Michelle R. ,   Barts Pancreas Tissue Bank, Dalli Jesmond , Kocher Hemant M.
Published: November 2023

Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a key driver of pancreatic ductal adenocarcinoma (PDAC) chemoresistance leading to poor prognosis. Specialized pro-resolving mediators (SPMs) are prime modulators of inflammation and its resolution, traditionally thought to be produced by immune cells. Using liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based lipid mediator profiling PSCs as well as primary human CAFs express enzymes and receptors to produce and respond to SPMs. Human PSC/CAF SPM secretion profile can be modulated by rendering these cells activated [transforming growth factor beta (TGF-β)] or quiescent [all-trans retinoic acid (ATRA)]. ATRA-induced nuclear translocation of arachidonate-15-lipoxygenase (ALOX15) was linked to increased production of n-3 docosapentaenoic acid-derived Resolvin D5 (RvD5n-3 DPA), among other SPMs. Inhibition of RvD5n-3 DPA formation increases cancer cell invasion, whereas addback of this molecule reduced activated PSC-mediated cancer cell invasion. We also observed that circulating concentrations of RvD5n-3 DPA levels were decreased in peripheral blood of metastatic PDAC patients when compared with those measured in plasma of non-metastatic PDAC patients. Together, these findings indicate that RvD5n-3 DPA may regulate cancer–stroma cross-talk and invasion.
Myeloid PFKFB3-mediated glycolysis promotes kidney fibrosis
Authors: Yang Qiuhua , Huo Emily , Cai Yongfeng , Zhang Zhidan , Dong Charles , Asara John M. , Shi Huidong , Wei Qingqing
Published: November 2023

Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. Inflammatory injury and aberrant repair processes contribute to the development of kidney fibrosis. Myeloid cells, particularly monocytes/macrophages, play a crucial role in kidney fibrosis by releasing their proinflammatory cytokines and extracellular matrix components such as collagen and fibronectin into the microenvironment of the injured kidney. Numerous signaling pathways have been identified in relation to these activities. However, the involvement of metabolic pathways in myeloid cell functions during the development of renal fibrosis remains understudied. In our study, we initially reanalyzed single-cell RNA sequencing data of renal myeloid cells from Dr. Denby’s group and observed an increased gene expression in glycolytic pathway in myeloid cells that are critical for renal inflammation and fibrosis. To investigate the role of myeloid glycolysis in renal fibrosis, we utilized a model of unilateral ureteral obstruction in mice deficient of Pfkfb3, an activator of glycolysis, in myeloid cells (Pfkfb3ΔMϕ) and their wild type littermates (Pfkfb3WT). We observed a significant reduction in fibrosis in the obstructive kidneys of Pfkfb3ΔMϕ mice compared to Pfkfb3WT mice. This was accompanied by a substantial decrease in macrophage infiltration, as well as a decrease of M1 and M2 macrophages and a suppression of macrophage to obtain myofibroblast phenotype in the obstructive kidneys of Pfkfb3ΔMϕ mice. Mechanistic studies indicate that glycolytic metabolites stabilize HIF1α, leading to alterations in macrophage phenotype that contribute to renal fibrosis. In conclusion, our study implicates that targeting myeloid glycolysis represents a novel approach to inhibit renal fibrosis.
Cerebrospinal fluid oligoclonal bands in Chinese patients with multiple sclerosis: the prevalence and its association with clinical features
Authors: Zhang Xiang , Hao Hongjun , Jin Tao , Qiu Wei , Yang Huan , Xue Qun , Yin Jian , Shi Ziyan , Yu Hai , Ji Xiaopei , Sun Xiaobo , Zeng Qiuming , Liu Xiaoni , Wang Jingguo , Li Huining , He Xiaoyan , Yang Jing , Li Yarong , Liu Shuangshuang , Lau Alexander Y. , Gao Feng , Hu Shimin , Chu Shuguang , Ding Ding , Zhou Hongyu , Li Haifeng , Chen Xiangjun
Published: November 2023

Background

Cerebrospinal fluid oligoclonal band (CSF-OCB) is an established biomarker in diagnosing multiple sclerosis (MS), however, there are no nationwide data on CSF-OCB prevalence and its diagnostic performance in Chinese MS patients, especially in the virtue of common standard operation procedure (SOP).

Methods

With a consensus SOP and the same isoelectric focusing system, we conducted a nationwide multi-center study on OCB status in consecutively, and recruited 483 MS patients and 880 non-MS patients, including neuro-inflammatory diseases (NID, n = 595) and non-inflammatory neurological diseases (NIND, n=285). Using a standardized case report form (CRF) to collect the clinical, radiological, immunological, and CSF data, we explored the association of CSF-OCB positivity with patient characters and the diagnostic performance of CSF-OCB in Chinese MS patients. Prospective source data collection, and retrospective data acquisition and statistical data analysis were used.

Findings

369 (76.4%) MS patients were OCB-positive, while 109 NID patients (18.3%) and 6 NIND patients (2.1%) were OCB-positive, respectively. Time from symptom onset to diagnosis was significantly shorter in OCB-positive than that in OCB-negative MS patients (13.2 vs 23.7 months, P=0.020). The prevalence of CSF-OCB in Chinese MS patients was significantly higher in high-latitude regions (41°-50°N)(P=0.016), and at high altitudes (>1000m)(P=0.025). The diagnostic performance of CSF-OCB differentiating MS from non-MS patients yielded a sensitivity of 76%, a specificity of 87%.

Interpretation

The nationwide prevalence of CSF-OCB was 76.4% in Chinese MS patients, and demonstrated a good diagnostic performance in differentiating MS from other CNS diseases. The CSF-OCB prevalence showed a correlation with high latitude and altitude in Chinese MS patients.
LRPAP1 is released from activated microglia and inhibits microglial phagocytosis and amyloid beta aggregation
Authors: Reid Kyle M. , Brown Guy C.
Published: November 2023

Low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1), also known as receptor associated protein (RAP), is an endoplasmic reticulum (ER) chaperone and inhibitor of LDL receptor related protein 1 (LRP1) and related receptors. These receptors have dozens of physiological ligands and cell functions, but it is not known whether cells release LRPAP1 physiologically at levels that regulate these receptors and cell functions. We used mouse BV-2 and human CHME3 microglial cell lines, and found that microglia released nanomolar levels of LRPAP1 when inflammatory activated by lipopolysaccharide or when ER stressed by tunicamycin. LRPAP1 was found on the surface of live activated and non-activated microglia, and anti-LRPAP1 antibodies induced internalization. Addition of 10 nM LRPAP1 inhibited microglial phagocytosis of isolated synapses and cells, and the uptake of Aβ. LRPAP1 also inhibited Aβ aggregation in vitro. Thus, activated and stressed microglia release LRPAP1 levels that can inhibit phagocytosis, Aβ uptake and Aβ aggregation. We conclude that LRPAP1 release may regulate microglial functions and Aβ pathology, and more generally that extracellular LRPAP1 may be a physiological and pathological regulator of a wide range of cell functions.
Gcm counteracts Toll-induced inflammation and impacts hemocyte number through cholinergic signaling
Authors: Bazzi Wael , Monticelli Sara , Delaporte Claude , Riet Céline , Giangrande Angela , Cattenoz Pierre B.
Published: November 2023

Hemocytes, the myeloid-like immune cells of Drosophila, fulfill a variety of functions that are not completely understood, ranging from phagocytosis to transduction of inflammatory signals. We here show that downregulating the hemocyte-specific Glial cell deficient/Glial cell missing (Glide/Gcm) transcription factor enhances the inflammatory response to the constitutive activation of the Toll pathway. This correlates with lower levels of glutathione S-transferase, suggesting an implication of Glide/Gcm in reactive oxygen species (ROS) signaling and calling for a widespread anti-inflammatory potential of Glide/Gcm. In addition, our data reveal the expression of acetylcholine receptors in hemocytes and that Toll activation affects their expressions, disclosing a novel aspect of the inflammatory response mediated by neurotransmitters. Finally, we provide evidence for acetylcholine receptor nicotinic acetylcholine receptor alpha 6 (nAchRalpha6) regulating hemocyte proliferation in a cell autonomous fashion and for non-cell autonomous cholinergic signaling regulating the number of hemocytes. Altogether, this study provides new insights on the molecular pathways involved in the inflammatory response.
Tumor-associated macrophages: an effective player of the tumor microenvironment
Authors: Basak Udit , Sarkar Tania , Mukherjee Sumon , Chakraborty Sourio , Dutta Apratim , Dutta Saikat , Nayak Debadatta , Kaushik Subhash , Das Tanya , Sa Gaurisankar
Published: November 2023

Cancer progression is primarily caused by interactions between transformed cells and the components of the tumor microenvironment (TME). TAMs (tumor-associated macrophages) make up the majority of the invading immune components, which are further categorized as anti-tumor M1 and pro-tumor M2 subtypes. While M1 is known to have anti-cancer properties, M2 is recognized to extend a protective role to the tumor. As a result, the tumor manipulates the TME in such a way that it induces macrophage infiltration and M1 to M2 switching bias to secure its survival. This M2-TAM bias in the TME promotes cancer cell proliferation, neoangiogenesis, lymphangiogenesis, epithelial-to-mesenchymal transition, matrix remodeling for metastatic support, and TME manipulation to an immunosuppressive state. TAMs additionally promote the emergence of cancer stem cells (CSCs), which are known for their ability to originate, metastasize, and relapse into tumors. CSCs also help M2-TAM by revealing immune escape and survival strategies during the initiation and relapse phases. This review describes the reasons for immunotherapy failure and, thereby, devises better strategies to impair the tumor–TAM crosstalk. This study will shed light on the understudied TAM-mediated tumor progression and address the much-needed holistic approach to anti-cancer therapy, which encompasses targeting cancer cells, CSCs, and TAMs all at the same time.
The associations between asthma and common comorbidities: a comprehensive Mendelian randomization study
Authors: Wang Xuezhao , Huang Yuchen , Li Xiaochen , He Yuanzhou , Liu Xiansheng
Published: November 2023

Background

Asthma is a chronic respiratory disease and is often associated with multiple comorbidities. The causal relationship between asthma and these comorbidities is still unclear. This study aimed to investigate the association between genetically predicted asthma and common comorbidities.

Methods

After searching PubMed and GWAS summary statistics, we identified 26 comorbidities of asthma. The causal relationship between asthma and comorbidities was assessed in two independent GWASs by bidirectional Mendelian randomization, followed by validation of the results using a multivariate Mendelian randomization analysis and several sensitivity analyses.

Results

In the bidirectional Mendelian randomization analysis, chronic sinusitis [odds ratio (OR) = 1.54, p = 1.40 × 10−5], atopic dermatitis (OR = 1.36, p = 9.37 × 10−21), allergic conjunctivitis (OR = 2.07, p = 4.32 × 10−6), and allergic rhinitis (OR = 1.53, p = 5.20 × 10−6) were significantly associated with increased asthma risk. Hyperthyroidism (OR = 1.12, p = 0.04) had a potential increased risk for asthma. For the reverse direction, asthma showed significant associations with an increased risk of chronic obstructive pulmonary disease (OR = 1.24, p = 2.25 × 10−9), chronic sinusitis (OR = 1.61, p = 5.25 × 10−21), atopic dermatitis (OR = 2.11, p = 1.24 × 10−24), allergic conjunctivitis (OR = 1.65, p = 6.66 × 10−35), allergic rhinitis (OR = 1.90, p = 2.38 × 10−57), and a potential higher risk of allergic urticaria (OR = 1.25, p = 0.003).

Conclusion

This study suggested a significant bidirectional association of chronic sinusitis, atopic dermatitis, allergic conjunctivitis, and allergic rhinitis with asthma. In addition, hyperthyroidism was associated with an increased risk of asthma and asthma increased the risk of chronic obstructive pulmonary disease and allergic urticaria.
Advances in psoriasis and gut microorganisms with co-metabolites
Authors: Zhu Qiushuang , Wu Kai , Yang Qiuhong , Meng Bo , Niu Yucun , Zhao Fenglian
Published: November 2023

This review summarizes the potential role of gut microbes and their metabolites as novel mediators of psoriasis, including their composition and function in disease pathogenesis, progression, and management. Gut microbiota network analysis, colony construction, and in vivo large-scale interaction experiments showed that different degrees of damage and repair in psoriasis, both in animals and humans, involve cross-border homeostasis of the microbial community. Which gut microbiota interactions are present in psoriasis and how they collaborate with immune cells and influence psoriasis development via the gut-skin axis remain incompletely elucidated. In this article, we review the latest information on the unique patterns of gut microbiota and co-metabolites involved in the pathogenesis of psoriasis and attempt to explore microbial-based therapeutic targets derived from mono-and polymicrobial probiotics, fecal microbiota transplantation, pharmacomicrobiomics, and dietary interventions as diagnostic or therapeutic approaches promising to provide new options and long-term management for psoriasis.
Host cell-based screening assays for identification of molecules targeting Pseudomonas aeruginosa cyclic di-GMP signaling and biofilm formation
Authors: Hu Ying , Webb Jeremy Stephen , An Shi-qi
Published: November 2023

The rapid emergence of bacterial resistance to antibiotics in current use is occurring worldwide and poses a significant threat to global healthcare systems. Recent research to identify new effective anti-bacterial agents has focused on regulatory pathways as targets for interference. Regulatory mechanisms employing intracellular Bis-(3′,5′) cyclic di-guanylate (c-di-GMP) as a secondary messenger represent a distinct category of subjects. This molecule, c-di-GMP, is present in nearly all bacterial species and plays a pivotal role in governing various biological processes, encompassing antibiotic resistance, biofilm formation, and virulence. Alteration of the cellular concentrations of the nucleotide through modulation of associated signaling pathways has the potential to reduce biofilm formation or increase susceptibility of the biofilm bacteria to antibiotics. Here, we have developed a screen for compounds that alter c-di-GMP levels in Pseudomonas aeruginosa in co-culture with bronchial epithelial cells. Through the assay of 200 natural compounds, we were able to identify several substances showing promising effects on P. aeruginosa in a host biofilm infection model. Importantly, we detected compounds that inhibit c-di-GMP levels and showed significant influence on biofilm formation and virulence in P. aeruginosa in vitro and in vivo. Consequently, we offer proof-of-concept information regarding swift and practical drug screening assays, suitable for medium- to high-throughput applications, which target the c-di-GMP signaling pathways in this significant Gram-negative pathogen.
Draft genome sequencing of Tilletia caries inciting common bunt of wheat provides pathogenicity-related genes
Authors: Gurjar Malkhan Singh , Kumar Tej Pratap Jitendra , Shakouka Mohamad Ayham , Saharan Mahender Singh , Rawat Laxmi , Aggarwal Rashmi
Published: November 2023

Common bunt of wheat caused by Tilletia caries is an important disease worldwide. The T. caries TC1_MSG genome was sequenced using the Illumina HiSeq 2500 and Nanopore ONT platforms. The Nanopore library was prepared using the ligation sequencing kit SQK-LSK110 to generate approximately 24 GB for sequencing. The assembly size of 38.18 Mb was generated with a GC content of 56.10%. The whole genome shotgun project was deposited at DDBJ/ENA/GenBank under the accession number JALUTQ000000000. Forty-six contigs were obtained with N50 of 1,798,756 bp. In total, 10,698 genes were predicted in the assembled genome. Out of 10,698 genes, 10,255 genes were predicted significantly in the genome. The repeat sequences made up approximately 1.57% of the genome. Molecular function, cellular components, and biological processes for predicted genes were mapped into the genome. In addition, repeat elements in the genome were assessed. In all, 0.89% of retroelements were observed, followed by long terminal repeat elements (0.86%) in the genome. In simple sequence repeat (SSR) analysis, 8,582 SSRs were found in the genome assembly. The trinucleotide SSR type (3,703) was the most abundant. Few putative secretory signal peptides and pathogenicity-related genes were predicted. The genomic information of T. caries will be valuable in understanding the pathogenesis mechanism as well as developing new methods for the management of the common bunt disease of wheat.
Rhizosphere microbial ecological characteristics of strawberry root rot
Authors: Zhang Meilin , Kong Zirong , Fu Huijing , Shu Xiaolong , Xue Quanhong , Lai Hangxian , Guo Qiao
Published: November 2023

Introduction

Strawberry (Fragaria × ananassa Duch.) holds a preeminent position among small fruits globally due to its delectable fruits and significant economic value. However, strawberry cultivation is hampered by various plant diseases, hindering the sustainable development of the strawberry industry. The occurrence of plant diseases is closely linked to imbalance in rhizosphere microbial community structure.

Methods

In the present study, a systematic analysis of the differences and correlations among non-culturable microorganisms, cultivable microbial communities, and soil nutrients in rhizosphere soil, root surface soil, and non-rhizosphere soil of healthy and diseased strawberry plants affected by root rot was conducted. The goal was to explore the relationship between strawberry root rot occurrence and rhizosphere microbial community structure.

Results

According to the results, strawberry root rot altered microbial community diversity, influenced fungal community composition in strawberry roots, reduced microbial interaction network stability, and enriched more endophytic-phytopathogenic bacteria and saprophytic bacteria. In addition, the number of bacteria isolated from the root surface soil of diseased plants was significantly higher than that of healthy plants.

Discussion

In summary, the diseased strawberry plants changed microbial community diversity, fungal species composition, and enriched functional microorganisms significantly, in addition to reshaping the microbial co-occurrence network. The results provide a theoretical basis for revealing the microecological mechanism of strawberry root rot and the ecological prevention and control of strawberry root rot from a microbial ecology perspective.
Carboxypeptidase inhibitors from Solanaceae as a new subclass of pathogenesis related peptide aiming biotechnological targets for plant defense
Authors: Gomes Geniana da Silva , Espósito Paula Corrêa , Baracat-Pereira Maria Cristina
Published: November 2023

Background: Plant protease inhibitors play a crucial role in inhibiting proteases produced by phytopathogens and exhibiting inhibitory effects on nematodes, fungi, and insects, making them promising candidates for crop protection. Specifically, carboxypeptidase inhibitors, a subset of proteinase inhibitors, have been extensively studied in potato and tomato of Solanaceae plant family. However, further research is needed to fully understand the functions and biotechnological potential of those inhibitors in plants. This work aimed to in silico characterize carboxypeptidase inhibitors from Solanaceae as potential antimicrobial and defense agents focused on biotechnological targets.

Methods: The methodology employed involved search in UniProt, PDB, KNOTTIN, NCBI, and MEROPS databases for solanaceous carboxypeptidase inhibitors, phylogenetic relationships and conservation patterns analyzes using MEGA-X software and Clustal Omega/MView tools, physicochemical properties and antimicrobial potential prediction using ProtParam, ToxinPred, iAMPred, and APD3 tools, and structural features prediction using PSIPRED.

Results and discussion: A systematic literature search was conducted to identify relevant studies on Solanaceae carboxypeptidase inhibitors and their activities against pathogens. The selected studies were reviewed and the main findings compiled. The characterization of Solanaceae carboxypeptidase inhibitors proposed for the first time the global sequence consensus motif CXXXCXXXXDCXXXXXCXXC, shedding light on carboxypeptidase inhibitors distribution, sequence variability, and conservation patterns. Phylogenetic analysis showed evolutionary relationships within the Solanaceae family, particularly in Capsicum, Nicotiana, and Solanum genera. Physicochemical characteristics of those peptides indicated their similarity to antimicrobial peptides. Predicted secondary structures exhibited variations, suggesting a broad spectrum of action, and studies had been demonstrated their activities against various pathogens.

Conclusion: Carboxypeptidase inhibitors are being proposed here as a new subclass of PR-6 pathogenesis-related proteins, which will aid in a focused understanding of their functional roles in plant defense mechanisms. These findings confirm the Solanaceae carboxypeptidase inhibitors potential as defense agents and highlight opportunities for their biotechnological applications in pathogen control.
An approach for assisting diagnosis of Alzheimer's disease based on natural language processing
Authors: Liu Ning , Wang Lingxing
Published: November 2023

Introduction

Alzheimer's Disease (AD) is a common dementia which affects linguistic function, memory, cognitive and visual spatial ability of the patients. Language is proved to have the relationship with AD, so the time that AD can be diagnosed in a doctor's office is coming.

Methods

In this study, the Pitt datasets are used to detect AD which is balanced in gender and age. First bidirectional Encoder Representation from Transformers (Bert) pretrained model is used to acquire the word vector. Then two channels are constructed in the feature extraction layer, which is, convolutional neural networks (CNN) and long and short time memory (LSTM) model to extract local features and global features respectively. The local features and global features are concatenated to generate feature vectors containing rich semantics, which are sent to softmax classifier for classification.

Results

Finally, we obtain a best accuracy of 89.3% which is comparative compared to other studies. In the meanwhile, we do the comparative experiments with TextCNN and LSTM model respectively, the combined model manifests best and TextCNN takes the second place.

Discussion

The performance illustrates the feasibility to predict AD effectively by using acoustic and linguistic datasets.
Hyperemia in head injury: can transcranial doppler help to personalize therapies for intracranial hypertension?
Authors: Gelormini Camilla , Ioannoni Eleonora , Scavone Angela , Pisapia Luca , Signorelli Francesco , Montano Nicola , Piastra Marco , Caricato Anselmo
Published: November 2023

Introduction

An increase in cerebral blood flow is frequent after traumatic brain injury (TBI) and can lead to brain swelling and refractory intracranial hypertension. We hypothesized that Transcranial EcoDoppler (TCD) monitoring could be useful to detect the cause of intracranial hypertension in these patients. Our main objective was to investigate if the increase of velocity in the middle cerebral artery (MCA) on TCD could be associated with intracranial hypertension.

Methods

We retrospectively studied TBI patients consecutively monitored with TCD. Hyperemia was defined as MCA mean velocity higher than 80 cm/s. Intracranial hypertension was considered when hyperosmolar therapy, hyperventilation, or deep sedation was used.

Results

We found hyperemia in 40 patients out of 118 (33.9%). On average, it started at day 2.1 ± 0.9 from admission and significantly increased (MCA velocity at day 1: 74 ± 25 cm/s vs. 109 ± 36 cm/s at day 4; p < 0.001). Intracranial hypertension was significantly associated with hyperemia, occurring in 92.5% of hyperemic and 51.3% of non-hyperemic patients (p < 0.001). Moreover, we found that hyperemia preceded severe intracranial hypertension (p < 0.0001). In a logistic regression model, hyperemia was the only variable significantly correlated with intracranial hypertension (OR 10.64; p < 0.001).

Discussion

Hyperemia was frequent in our population of TBI patients and preceded intracranial hypertension. TCD monitoring, if performed on a daily regular basis, can be a useful method to detect this phenomenon and to guide the therapy. It could be a tool for a cause-oriented therapy of intracranial hypertension.
Polyherbal formulation PL02 alleviates pain, inflammation, and subchondral bone deterioration in an osteoarthritis rodent model
Authors: Upadhyay Prabhat , Kalra Diya , Nilakhe Aishwarya Shrikant , Aggrawal Vijay , Gupta Sarika
Published: November 2023

Introduction

Osteoarthritis (OA) is a debilitating disease with significant personal and socioeconomic burdens worldwide.

Methods

To address this, we developed a multitargeted formulation called PL02, which includes standardized extracts of Rosa canina L, Hippophae rhamnoides, and collagen peptide. We tested the pharmacological efficacy of PL02 in a rodent model of OA induced by Monosodium iodoacetate (MIA).

Results

Our results demonstrate that oral administration of PL02 has antioxidant effects by down-regulating NOS, reduces pain-related behavior, and mitigates inflammation by inhibiting IL-1b and TNF-α production, as well as downregulating CGRP1 and COX-II. PL02 also exhibits anti-catabolic and chondroprotective activity by significantly downregulating MMP13 and upregulating BCL2. Additionally, PL02 demonstrates chondrogenic activity by significantly upregulating SOX-9 (a master regulator of chondrogenesis), Coll-I, and aggrecan, which are major components of articular cartilage. Furthermore, PL02 prevents microarchitectural deterioration of subchondral bone.

Conclusion

Overall, PL02 is an orally active, multi-targeted therapy that not only alleviates pain and inflammation but also effectively halts cartilage and subchondral bone deterioration. It represents a safe and promising candidate for the treatment and management of OA.
Genetic variant panel allows predicting both obesity risk, and efficacy of procedures and diet in weight loss
Authors: Mera-Charria Alejandra , Nieto-Lopez Francisco , Francès Manel Pacareu , Arbex Priscila Marques , Vila-Vecilla Laura , Russo Valentina , Silva Carolina Costa Vicente , De Souza Gustavo Torres
Published: November 2023

Purpose

Obesity is a multifactorial condition with a relevant genetic correlation. Recent advances in genomic research have identified several single nucleotide polymorphisms (SNPs) in genes such as FTO, MCM6, HLA, and MC4R, associated with obesity. This study aimed to evaluate the association of 102 SNPs with BMI and weight loss treatment response in a multi-ethnic population.

Methods

The study analyzed 9,372 patients for the correlation between SNPs and BMI (dataset A). The correlation between SNP and weight loss was accessed in 474 patients undergoing different treatments (dataset B). Patients in dataset B were further divided into 3 categories based on the type of intervention: dietary therapy, intragastric balloon procedures, or surgeries. SNP association analysis and multiple models of inheritance were performed.

Results

In dataset A, ten SNPs, including rs9939609 (FTO), rs4988235 (MCM6), and rs2395182 (HLA), were significantly associated with increased BMI. Additionally, other four SNPs, rs7903146 (TCF7L2), (rs6511720), rs5400 (SLC2A2), and rs7498665 (SH2B1), showed sex-specific correlation. For dataset B, SNPs rs2016520 (PPAR-Delta) and rs2419621 (ACSL5) demonstrated significant correlation with weight loss for all treatment types. In patients who adhered to dietary therapy, SNPs rs6544713 (ABCG8) and rs762551 (CYP1A2) were strongly correlated with weight loss. Patients undergoing surgical or endoscopic procedures exhibited differential correlations with several SNPs, including rs1801725 (CASR) and rs12970134 (MC4R), and weight loss.

Conclusion

This study provides valuable insights into the genetic factors influencing BMI and weight loss response to different treatments. The findings highlight the potential for personalized weight management approaches based on individual genetic profiles.
Construction of a risk scoring system using clinical factors and RYR2 polymorphisms for bleeding complications in patients on direct oral anticoagulants
Authors: Jang Eun Jeong , Kim Jung Sun , Choi Seo A. , Yee Jeong , Song Tae-Jin , Park Junbeom , Gwak Hye Sun
Published: November 2023

Introduction: Bleeding is one of the most undesirable complications of direct oral anticoagulants (DOACs). While the ryanodine receptor (RYR2) has been related to cardiac diseases, research on bleeding complications is lacking. This study aimed to elucidate the association between RYR2 and bleeding risk to develop the risk scoring system in patients treated with DOACs.

Methods: This study was a retrospective analysis of prospectively collected samples. We selected ten SNPs within the RYR2 gene, and two models were constructed (Model I: demographic factors only, Model II: demographic and genetic factors) in multivariable analysis. Independent risk factors for bleeding were used to develop a risk scoring system.

Results: A total of 447 patients were included, and 49 experienced either major bleeding or clinically relevant non-major bleeding. In Model I, patients using rivaroxaban and experiencing anemia exhibited an increased bleeding risk after adjusting for covariates. Upon incorporating genetic factors into Model I, a significant association with bleeding was also observed in cases of overdosing on DOACs and in patients with a creatinine clearance (CrCl) < 30 mL/min, in addition to rivaroxaban and anemia (Model II). Among genetic factors, RYR2 rs12594 GG, rs17682073 AA, rs3766871 GG, and rs6678625 T alleles were associated with bleeding complications. The area under the receiver operating characteristic curve (AUROC) of Model I was 0.670, whereas that of Model II increased to 0.803, demonstrating better performance with the inclusion of genetic factors. Using the significant variables in Model II, a risk scoring system was constructed. The predicted bleeding risks for scores of 0, 1–2, 3–4, 5–6, 7–8, and 9–10 points were 0%, 1.2%, 4.6%, 15.7%, 41.7%, and 73.3%, respectively.

Conclusion: This study revealed an association between RYR2 and bleeding complications among patients taking DOACs and established a risk scoring system to support individualized DOAC treatment for these patients.
Effect of standard and physiological cell culture temperatures on in vitro proliferation and differentiation of primary broiler chicken pectoralis major muscle satellite cells
Authors: Gregg Caroline R. , Hutson Brittany L. , Flees Joshua J. , Starkey Charles W. , Starkey Jessica D.
Published: November 2023

Culture temperatures for broiler chicken cells are largely based on those optimized for mammalian species, although normal broiler body temperature is typically more than 3°C higher. The objective was to evaluate the effects of simulating broiler peripheral muscle temperature, 41°C, compared with standard temperature, 38°C, on the in vitro proliferation and differentiation of primary muscle-specific stem cells (satellite cells; SC) from the pectoralis major (PM) of broiler chickens. Primary SC cultures were isolated from the PM of 18-day-old Ross 708 × Yield Plus male broilers. SC were plated in triplicate, 1.8-cm2, gelatin-coated wells at 40,000 cells per well. Parallel plates were cultured at either 38°C or 41°C in separate incubators. At 48, 72, and 96 h post-plating, the culture wells were fixed and immunofluorescence-stained to determine the expression of the myogenic regulatory factors Pax7 and MyoD as well as evaluated for apoptosis using a TUNEL assay. After 168 h in culture, plates were immunofluorescence-stained to visualize myosin heavy chain and Pax7 expression and determine myotube characteristics and SC fusion. Population doubling times were not impacted by temperature (p ≥ 0.1148), but culturing broiler SC at 41°C for 96 h promoted a more rapid progression through myogenesis, while 38°C maintained primitive populations (p ≤ 0.0029). The proportion of apoptotic cells increased in primary SC cultured at 41°C (p ≤ 0.0273). Culturing at 41°C appeared to negatively impact fusion percentage (p < 0.0001) and tended to result in the formation of thinner myotubes (p = 0.061) without impacting the density of differentiated cells (p = 0.7551). These results indicate that culture temperature alters primary broiler PM SC myogenic kinetics and has important implications for future in vitro work as well as improving our understanding of how thermal manipulation can alter myogenesis patterns during broiler embryonic and post-hatch muscle growth.
γ-Aminobutyric acid is involved in overlapping pathways against chilling injury by modulating glutamate decarboxylase and defense responses in papaya fruit
Authors: Khaliq Ghulam , Ali Sajid , Ejaz Shaghef , Abdi Gholamreza , Faqir Yahya , Ma Jiahua , Siddiqui Mohammed Wasim , Ali Asgar
Published: November 2023

The effect of γ-aminobutyric acid (GABA) treatment at two concentrations (1 mM or 5 mM) on papaya fruit stored at 4°C and 80%–90% relative humidity for 5 weeks was investigated. The application of GABA at 5 mM apparently inhibited chilling injury, internal browning, electrolyte leakage, malondialdehyde (MDA), hydrogen peroxide (H2O2), polyphenol oxidase (PPO), phospholipase D (PLD), and lipoxygenase (LOX) activities of papaya fruit. Fruit treated with 5 mM GABA enhanced the activities of ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutamate decarboxylase (GAD), and phenylalanine ammonia-lyase (PAL). In addition, GABA treatment significantly displayed higher levels of proline, endogenous GABA accumulation, phenolic contents, and total antioxidant activity than the nontreated papaya. The results suggested that GABA treatment may be a useful approach to improving the chilling tolerance of papaya fruit by reducing oxidative stress and enhancing the defense system.
The unequal functional redundancy of Arabidopsis INCURVATA11 and CUPULIFORMIS2 is not dependent on genetic background
Authors: Nadi Riad , Juan-Vicente Lucía , Mateo-Bonmatí Eduardo , Micol José Luis
Published: November 2023

The paralogous genes INCURVATA11 (ICU11) and CUPULIFORMIS2 (CP2) encode components of the epigenetic machinery in Arabidopsis and belong to the 2-oxoglutarate and Fe (II)-dependent dioxygenase superfamily. We previously inferred unequal functional redundancy between ICU11 and CP2 from a study of the synergistic phenotypes of the double mutant and sesquimutant combinations of icu11 and cp2 mutations, although they represented mixed genetic backgrounds. To avoid potential confounding effects arising from different genetic backgrounds, we generated the icu11-5 and icu11-6 mutants via CRISPR/Cas genome editing in the Col-0 background and crossed them to cp2 mutants in Col-0. The resulting mutants exhibited a postembryonic-lethal phenotype reminiscent of strong embryonic flower (emf) mutants. Double mutants involving icu11-5 and mutations affecting epigenetic machinery components displayed synergistic phenotypes, whereas cp2-3 did not besides icu11-5. Our results confirmed the unequal functional redundancy between ICU11 and CP2 and demonstrated that it is not allele or genetic background specific. An increase in sucrose content in the culture medium partially rescued the post-germinative lethality of icu11 cp2 double mutants and sesquimutants, facilitating the study of their morphological phenotypes throughout their life cycle, which include floral organ homeotic transformations. We thus established that the ICU11-CP2 module is required for proper flower organ identity.
Cold stress induces differential gene expression of retained homeologs in Camelina sativa cv Suneson
Authors: Fang Chao , Hamilton John P. , Vaillancourt Brieanne , Wang Yi-Wen , Wood Joshua C. , Deans Natalie C. , Scroggs Taylor , Carlton Lemor , Mailloux Kathrine , Douches David S. , Nadakuduti Satya Swathi , Jiang Jiming , Buell C. Robin
Published: November 2023

Camelina sativa (L.) Crantz, a member of the Brassicaceae, has potential as a biofuel feedstock which is attributable to the production of fatty acids in its seeds, its fast growth cycle, and low input requirements. While a genome assembly is available for camelina, it was generated from short sequence reads and is thus highly fragmented in nature. Using long read sequences, we generated a chromosome-scale, highly contiguous genome assembly (644,491,969 bp) for the spring biotype cultivar ‘Suneson’ with an N50 contig length of 12,031,512 bp and a scaffold N50 length of 32,184,682 bp. Annotation of protein-coding genes revealed 91,877 genes that encode 133,355 gene models. We identified a total of 4,467 genes that were significantly up-regulated under cold stress which were enriched in gene ontology terms associated with “response to cold” and “response to abiotic stress”. Coexpression analyses revealed multiple coexpression modules that were enriched in genes differentially expressed following cold stress that had putative functions involved in stress adaptation, specifically within the plastid. With access to a highly contiguous genome assembly, comparative analyses with Arabidopsis thaliana revealed 23,625 A. thaliana genes syntenic with 45,453 Suneson genes. Of these, 24,960 Suneson genes were syntenic to 8,320 A. thaliana genes reflecting a 3 camelina homeolog to 1 Arabidopsis gene relationship and retention of all three homeologs. Some of the retained triplicated homeologs showed conserved gene expression patterns under control and cold-stressed conditions whereas other triplicated homeologs displayed diverged expression patterns revealing sub- and neo-functionalization of the homeologs at the transcription level. Access to the chromosome-scale assembly of Suneson will enable both basic and applied research efforts in the improvement of camelina as a sustainable biofuel feedstock.
Chromosome-level changes and genome elimination by manipulation of CENH3 in carrot (Daucus carota)
Authors: Meyer Chandler M. , Goldman Irwin L. , Krysan Patrick J.
Published: November 2023

Hybrid cultivars are valuable in many crop species due to their high yield, uniformity, and other desirable traits. Doubled haploids, which have two identical sets of chromosomes, are valuable for hybrid breeding because they can be produced in one generation, in comparison to the multigenerational process typically used to produce inbred parents for hybrid production. One method to produce haploid plants is manipulation of centromeric histone H3 (CENH3). This method of producing haploids has so far been successful in Arabidopsis, maize (Zea mays), and wheat (Triticum aestivum). Here we describe modification of CENH3 in carrot (Daucus carota) to test for the ability of these modifications to induce uniparental genome elimination, which is the basis for haploid induction. Base editing was used to make cenh3 mutant plants with amino acid substitutions in the region of CENH3 encoding the histone fold domain. These cenh3 mutant plants were then outcrossed with CENH3 wild-type plants. Using PCR-based genotyping assays, we identified two candidates for genome elimination. One candidate was classified as a putative aneuploid plant in which chromosome 7 is in a single copy state. The other candidate was characterized as a putative tetraploid that was likely haploid during its genesis. Our results suggest that this putative tetraploid inherited all of its chromosomes from the CENH3 wild-type parent and that the genome of the cenh3 mutant plant was lost. This study provides evidence that modification of CENH3 in carrot has the potential to induce genome elimination and ploidy changes in carrot.
The heavy-tailed valence hypothesis: the human capacity for vast variation in pleasure/pain and how to test it
Authors: Gómez-Emilsson Andrés , Percy Chris
Published: November 2023

Introduction

Wellbeing policy analysis is often criticized for requiring a cardinal interpretation of measurement scales, such as ranking happiness on an integer scale from 0-10. The commonly-used scales also implicitly constrain the human capacity for experience, typically that our most intense experiences can only be at most ten times more intense than our mildest experiences. This paper presents the alternative “heavy-tailed valence” (HTV) hypothesis: the notion that the accessible human capacity for emotional experiences of pleasure and pain spans a minimum of two orders of magnitude.

Methods

We specify five testable predictions of the HTV hypothesis. A pilot survey of adults aged 21-64 (n = 97) then tested two predictions, asking respondents to comment on the most painful and most pleasurable experiences they can recall, alongside the second most painful and pleasurable experiences.

Results

The results find tentative support for the hypothesis. For instance, over half of respondents said their most intense experiences were at least twice as intense as the second most intense, implying a wide capacity overall. Simulations further demonstrate that survey responses are more consistent with underlying heavy-tailed distributions of experience than a “constrained valence” psychology.

Discussion

A synthesis of these results with prior findings suggests a “kinked” scale, such that a wide range of felt experience is compressed in reports at the high end of intensity scales, even if reports at lower intensities behave more cardinally. We present a discussion of three stylized facts that support HTV and six against, lessons for a future survey, practical guidelines for existing analyses, and implications for current policy. We argue for a dramatic increase in societal ambition. Even in high average income countries, the HTV hypothesis suggests we remain far further below our wellbeing potential than a surface reading of the data might suggest.
Perceptions of poverty in Spain: differences in the attitudinal profiles between women and men
Authors: Terol Cantero M. Carmen , Martin-Aragón Gelabert Maite , Vázquez Rodríguez Carolina , Lledó Boyer Ana , García Soler Jose Enrique
Published: November 2023

Poverty is a multidimensional phenomenon that encompasses privation of education, health or housing. Women show more positive perceptions of poor people, making external attributions for the causes of poverty or the circumstances that explain it. The aim of this study is to analyse perceptions of poverty, identifying the differences in attitudinal profiles between women and men, and the influence of their political and religious beliefs. The sample consists of 278 participants (154 women and 124 men), who completed a sociodemographic questionnaire and the Scale of Attitudes and Stereotypes toward Poverty. The results showed two attitude profiles for women and men, with differences in the first profile, where women or men did not have religious beliefs, had left-wing or centre-left political ideas and favourable attitudes about poverty.
Validation study for the Academic Maladjustment Questionnaire on a Romanian sample
Authors: Cazan Ana-Maria , Stan Maria Magdalena , Clinciu Aurel Ion , Truţa Camelia , Maican Catalin Ioan
Published: November 2023

Introduction

The problem of academic dropout in the first year of studies represents an important issue for higher education, in that it accounts for an important indicator of quality but also for the negative consequences it produces on individual, institutional and social level. The main aim of the study is to validate and evaluate a robust measure of overall academic maladjustment.

Method

The participants were 809 first-year students from various Romanian universities.

Results

The results showed a reliable version of the instrument with a factorial structure that did not deviate significantly from the authors’ initial model. The exploratory and confirmatory factor analysis revealed a unified score including six dimensions, procrastination, dishonesty – unethical behavior, test anxiety, machiavellian attitude, neuroticism, and somatization. Our results confirmed that besides academic achievement, personal factors are important indicators of adjustment, showing that personal resources management, emotional and behavioral strategies are components of adjustment. Our study revealed a medium and positive correlation between overall maladjustment and academic dropout intention, procrastination seemed to be the most relevant predictor of dropout intention.

Discussion

Academic adjustment acts as a safeguard against dropping out, and it is crucial to acknowledge that most students enter college with the intention of completing their studies.