bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet-Rich Plasma Applications, The Past 5 Years: A Review Article
Authors: Buontempo Michael , Alhanshali Lina , Shapiro Jerry , Sicco Kristen , Garshick Michael
Published: November 2023

Platelet-rich plasma (PRP) is autologous plasma with a platelet concentration that is on average five times greater than baseline, and has been extensively investigated for its potential applications across various medical fields, including orthopaedics, dermatology, wound healing, maxillofacial surgery, and others. This review article aims to provide an overview of PRP’s applications and evidence over the past 5 years in randomised controlled trials. Many studies demonstrate PRP’s effectiveness in reducing pain and improving functional outcomes, while others report no significant differences compared to alternative treatments or placebo. Across various studies, several key limitations exist, such as small sample sizes, short follow-up durations, and lack of standardisation in PRP preparation methods, highlighting the need for research to further establish PRP’s effectiveness in these clinical applications. The article also discusses the different classification systems for PRP, and underscores the importance of understanding the components that influence clinical outcomes, as well as noting the growth of PRP in the marketplace. Overall, while studies exist demonstrating the clinical utility of PRP, standardised reporting is required to determine its full potential, as well as optimal preparation and administration strategies.
“Our very prison this earth is”: the world as prison and other images common to More's Epigrams and later works
Authors: Ritter Bradley
Published: November 2023

More's Epigrams of 1518, usually associated with More's humanist phase, contain a number of poems designed as meditations on proper attitudes towards the goods of fortune. Special attention is given to how phrasing and argumentation used in the Epigrams reappears within a number of More's later works, including Last Things, Treatise on the Passion, and A Dialogue of Comfort against Tribulation. Both briefer and longer examples are discussed, the latter including More's more elaborate description of the world as prison (Epigram 119) and fame as an insubstantial wind (Epigram 132). Numerous parallels between the arguments of these epigrams and his later works, written for “spirituall profytt” ( The Correspondence of Sir Thomas More, ed. Elizabeth Frances Rogers [Princeton, NJ: Princeton University Press, 1947], 531), are examined, giving us insights into the writings of the humanist More. As much of his earlier English poetry, some of the More's Latin poems were written with an eye towards “the happy continuannce and graciouse encreace of vertue” ( CW 1:51/20–21)
The prison analogy in Thomas More's A Dialogue of Comfort against Tribulation
Authors: Avery Joshua
Published: November 2023

This essay argues for a particular purpose in the section of the Dialogue during which Anthony argues to Vincent that the world is, properly understood, a prison. Anthony, in the vein of Socrates, challenges Vincent by presenting questions and arguments—sometimes even deliberately simplified arguments—that force Vincent into a deeper engagement with the relevant issues, and hence to an improved clarity. Specifically, Anthony Socratically pushes Vincent better to appreciate the enormous gulfs between human and divine perspectives on the relevant issues. By realizing the limits of his own human-centered assumptions, Vincent is able to deepen and elevate his understanding of the points at hand. It is by means of this new orientation that Vincent is able to find peace, a victory over his passions, as is implied by the Latin word for “conquer” embedded in his name.
A rigorous proof of the Riemann hypothesis
Authors: Abe Yukitaka
Published: November 2023

We prove the Riemann hypothesis by a new analytic approach.
Case Report: The application of metagenomic next generation sequencing in diagnosing fungal malignant external otitis: a report of two cases
Authors: Wang Qi , Hu Rui , Zhu YiFan , Zhu WenQing , Jiang Hua
Published: November 2023

Background

Most of malignant external otitis (MEO) cases reported in the literature are attributed to Pseudomonas aeruginosa. Fungal infections in MEO are also likely but extremely rare. And conventional microbiology tests is difficult to diagnose.

Case description

Two patients were diagnosed with Fungal malignant external otitis (FMEO) due to Aspergillus by metagenomic Next-Generation Sequencing (mNGS) and recovered after comprehensive treatment including operation and voriconazole. The antifungal treatment was delayed due to repeated cultures of secretions being negative and pathological examination showed granulation tissue proliferation with extensive neutrophil infiltration.

Conclusion

mNGS might be helpful for patients suspected with FMEO, especially when conventional microbiology tests were negative.
The patatin-like phospholipase PfPNPLA2 is involved in the mitochondrial degradation of phosphatidylglycerol during Plasmodium falciparum blood stage development
Authors: Shunmugam Serena , Quansah Nyamekye , Flammersfeld Ansgar , Islam Md Muzahidul , Sassmannshausen Juliane , Bennink Sandra , Yamaryo-Botté Yoshiki , Pradel Gabriele , Botté Cyrille Y.
Published: November 2023

Plasmodium falciparum is an Apicomplexa responsible for human malaria, a major disease causing more than ½ million deaths every year, against which there is no fully efficient vaccine. The current rapid emergence of drug resistances emphasizes the need to identify novel drug targets. Increasing evidences show that lipid synthesis and trafficking are essential for parasite survival and pathogenesis, and that these pathways represent potential points of attack. Large amounts of phospholipids are needed for the generation of membrane compartments for newly divided parasites in the host cell. Parasite membrane homeostasis is achieved by an essential combination of parasite de novo lipid synthesis/recycling and massive host lipid scavenging. Latest data suggest that the mobilization and channeling of lipid resources is key for asexual parasite survival within the host red blood cell, but the molecular actors allowing lipid acquisition are poorly characterized. Enzymes remodeling lipids such as phospholipases are likely involved in these mechanisms. P. falciparum possesses an unusually large set of phospholipases, whose functions are largely unknown. Here we focused on the putative patatin-like phospholipase PfPNPLA2, for which we generated an glmS-inducible knockdown line and investigated its role during blood stages malaria. Disruption of the mitochondrial PfPNPLA2 in the asexual blood stages affected mitochondrial morphology and further induced a significant defect in parasite replication and survival, in particular under low host lipid availability. Lipidomic analyses revealed that PfPNPLA2 specifically degrades the parasite membrane lipid phosphatidylglycerol to generate lysobisphosphatidic acid. PfPNPLA2 knockdown further resulted in an increased host lipid scavenging accumulating in the form of storage lipids and free fatty acids. These results suggest that PfPNPLA2 is involved in the recycling of parasite phosphatidylglycerol to sustain optimal intraerythrocytic development when the host resources are scarce. This work strengthens our understanding of the complex lipid homeostasis pathways to acquire lipids and allow asexual parasite survival.
Case report: A new de novo mutation of the Troponin T2 gene in a Chinese patient with dilated cardiomyopathy
Authors: Yang Huan , Gong Ke , Luo Yong , Wang Lei , Tan Zhiping , Yao Yao , Xie Li
Published: November 2023

Dilated cardiomyopathy (DCM) is a cardiovascular disease characterized by persistent ventricular dilatation and systolic dysfunction. DCM has a variety of causes, including myocarditis; exposure to narcotics, alcohol, or other toxins; and metabolic or endocrine disorders. Genetic factors play a dominant role in 30%–40% of DCM cases. Here, we report a case of DCM with very severe heart failure. Because of the severity of heart failure, the patient underwent heart transplantation. We speculated that the patient's DCM might be due to a mutation; hence, we performed whole-exome sequencing of the patient and their parents, which showed a de novo heterozygous mutation (NM_001001431.2c.769G>A:p.E257K) in TNNT2, which was considered pathogenic according to the ACMG pathogenicity assessment. This finding expands the genetic map of DCM and TNNT2 and will be important for future studies on the genetic and disease relationships between DCM and TNNT2.
Small course interventions focused on whole-person development increase aspects of student affect for women, Asian and first-generation students
Authors: Miller Elias , Withers Michelle
Published: November 2023

Students from historically excluded groups are more likely to persist in STEM if they believe that what they learn can provide them with tools to better their communities. One way to achieve this is to contextualize course content in ways that empower students to develop positive identities with science. Given the disproportionate ostracism of persons excluded based on ethnicity or race (PEERs) from STEM degree programs, we examined student responses to incorporating modules that emphasized either the relevance of course content or whole-person development into discussion sections of a large-enrollment introductory environmental sciences course. Reflection activities in the relevance sections emphasized how the course content related to societal problems of interest, while reflection activities in the whole-person development sections focused on how to use college and career to live a fulfilled, productive life. To measure the impact of these different reflection modules, we administered pre−/post-surveys with questions that queried life satisfaction, science motivation, sense of belonging, and expectations for college. Results demonstrate that women, Asian students, and students with neither parent attending college demonstrated significant increases in specific aspects of student affect like personal science motivation, life satisfaction and/or sense of belonging regardless of intervention type. Small psycho-social interventions like these can be added to existing course structures to improve student affect and potentially serve as a steppingstone to bigger course reforms.
Identification of key genes and pathways in adrenocortical carcinoma: evidence from bioinformatic analysis
Authors: Yin Mengsha , Wang Yao , Ren Xinhua , Han Mingyue , Li Shanshan , Liang Ruishuang , Wang Guixia , Gang Xiaokun
Published: November 2023

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The disease originates from the cortex of adrenal gland and lacks effective treatment. Efforts have been made to elucidate the pathogenesis of ACC, but the molecular mechanisms remain elusive. To identify key genes and pathways in ACC, the expression profiles of GSE12368, GSE90713 and GSE143383 were downloaded from the Gene Expression Omnibus (GEO) database. After screening differentially expressed genes (DEGs) in each microarray dataset on the basis of cut-off, we identified 206 DEGs, consisting of 72 up-regulated and 134 down-regulated genes in three datasets. Function enrichment analyses of DEGs were performed by DAVID online database and the results revealed that the DEGs were mainly enriched in cell cycle, cell cycle process, mitotic cell cycle, response to oxygen-containing compound, progesterone-mediated oocyte maturation, p53 signaling pathway. The STRING database was used to construct the protein–protein interaction (PPI) network, and modules analysis was performed using Cytoscape. Finally, we filtered out eight hub genes, including CDK1, CCNA2, CCNB1, TOP2A, MAD2L1, BIRC5, BUB1 and AURKA. Biological process analysis showed that these hub genes were significantly enriched in nuclear division, mitosis, M phase of mitotic cell cycle and cell cycle process. Violin plot, Kaplan-Meier curve and stage plot of these hub genes confirmed the reliability of the results. In conclusion, the results in this study provided reliable key genes and pathways for ACC, which will be useful for ACC mechanisms, diagnosis and candidate targeted treatment.
GLP-1 RAs and SGLT2i: two antidiabetic agents associated with immune and inflammation modulatory properties through the common AMPK pathway
Authors: Mazzieri Alessio , Basta Giuseppe , Calafiore Riccardo , Luca Giovanni
Published: November 2023

Immune cells and other cells respond to nutrient deprivation by the classic catabolic pathway of AMPK (Adenosine monophosphate kinase). This kinase is a pivotal regulator of glucose and fatty acids metabolism, although current evidence highlights its role in immune regulation. Indeed AMPK, through activation of Foxo1 (Forkhead box O1) and Foxo3 (Forkhead box O3), can regulate FOXP3, the key gene for differentiation and homeostasis of Tregs (T regulators lymphocytes). The relevance of Tregs in the onset of T1D (Type 1 diabetes) is well-known, while their role in the pathogenesis of T2D (Type 2 diabetes) is not fully understood yet. However, several studies seem to indicate that Tregs may oppose the progression of diabetic complications by mitigating insulin resistance, atherosclerosis, and damage to target organs (as in kidney disease). Hence, AMPK and AMPK-activating agents may play a role in the regulation of the immune system. The connection between metformin and AMPK is historically known; however, this link and the possible related immune effects are less studied about SGLT2i (Sodium-glucose co-transport 2 inhibitors) and GLP1-RAs (Glucagon-like peptide-1 receptor agonists). Actual evidence shows that the negative caloric balance, induced by SGLT2i, can activate AMPK. Conversely and surprisingly, an anabolizing agent like GLP-1RAs can also upregulate this kinase through cAMP (Cyclic adenosine monophosphate) accumulation. Therefore, both these drugs can likely lead to the activation of the AMPK pathway and consequential proliferation of Tregs. These observations seem to confirm not only the metabolic but also the immunoregulatory effects of these new antidiabetic agents.
The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications
Authors: Li Delun , Yuan Siyu , Deng Yiyao , Wang Xiaowan , Wu Shouhai , Chen Xuesheng , Li Yimeng , Ouyang Jianting , Lin Danyao , Quan Haohao , Fu Xinwen , Li Chuang , Mao Wei
Published: November 2023

Changes in lifestyle induce an increase in patients with hyperuricemia (HUA), leading to gout, gouty arthritis, renal damage, and cardiovascular injury. There is a strong inflammatory response in the process of HUA, while dysregulation of immune cells, including monocytes, macrophages, and T cells, plays a crucial role in the inflammatory response. Recent studies have indicated that urate has a direct impact on immune cell populations, changes in cytokine expression, modifications in chemotaxis and differentiation, and the provocation of immune cells by intrinsic cells to cause the aforementioned conditions. Here we conducted a detailed review of the relationship among uric acid, immune response, and inflammatory status in hyperuricemia and its complications, providing new therapeutic targets and strategies.
Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins
Authors: Frauenlob Tobias , Neuper Theresa , Regl Christof , Schaepertoens Veronika , Unger Michael S. , Oswald Anna-Lena , Dang Hieu-Hoa , Huber Christian G. , Aberger Fritz , Wessler Silja , Horejs-Hoeck Jutta
Published: November 2023

Helicobacter pylori is a widespread Gram-negative pathogen involved in a variety of gastrointestinal diseases, including gastritis, ulceration, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. Immune responses aimed at eradication of H. pylori often prove futile, and paradoxically play a crucial role in the degeneration of epithelial integrity and disease progression. We have previously shown that H. pylori infection of primary human monocytes increases their potential to respond to subsequent bacterial stimuli – a process that may be involved in the generation of exaggerated, yet ineffective immune responses directed against the pathogen. In this study, we show that H. pylori-induced monocyte priming is not a common feature of Gram-negative bacteria, as Acinetobacter lwoffii induces tolerance to subsequent Escherichia coli lipopolysaccharide (LPS) challenge. Although the increased reactivity of H. pylori-infected monocytes seems to be specific to H. pylori, it appears to be independent of its virulence factors Cag pathogenicity island (CagPAI), cytotoxin associated gene A (CagA), vacuolating toxin A (VacA) and γ-glutamyl transferase (γ-GT). Utilizing whole-cell proteomics complemented with biochemical signaling studies, we show that H. pylori infection of monocytes induces a unique proteomic signature compared to other pro-inflammatory priming stimuli, namely LPS and the pathobiont A. lwoffii. Contrary to these tolerance-inducing stimuli, H. pylori priming leads to accumulation of NF-кB proteins, including p65/RelA, and thus to the acquisition of a monocyte phenotype more responsive to subsequent LPS challenge. The plasticity of pro-inflammatory responses based on abundance and availability of intracellular signaling molecules may be a heretofore underappreciated form of regulating innate immune memory as well as a novel facet of the pathobiology induced by H. pylori.
Overall avidity declines in TCR repertoires during latent CMV but not EBV infection
Authors: Couturaud Barbara , Doix Bastien , Carretero-Iglesia Laura , Allard Mathilde , Pradervand Sylvain , Hebeisen Michael , Rufer Nathalie
Published: November 2023

Introduction

The avidity of the T-cell receptor (TCR) for antigenic peptides presented by the MHC (pMHC) on cells is an essential parameter for efficient T cell-mediated immunity. Yet, whether the TCR-ligand avidity can drive the clonal evolution of virus antigen-specific CD8 T cells, and how this process is determined in latent Cytomegalovirus (CMV)- against Epstein-Barr virus (EBV)-mediated infection remains largely unknown.

Methods

To address these issues, we quantified monomeric TCR-pMHC dissociation rates on CMV- and EBV-specific individual TCRαβ clonotypes and polyclonal CD8 T cell populations in healthy donors over a follow-up time of 15-18 years. The parameters involved during the long-term persistence of virus-specific T cell clonotypes were further evaluated by gene expression profiling, phenotype and functional analyses.

Results

Within CMV/pp65-specific T cell repertoires, a progressive contraction of clonotypes with high TCR-pMHC avidity and low CD8 binding dependency was observed, leading to an overall avidity decline during long-term antigen exposure. We identified a unique transcriptional signature preferentially expressed by high-avidity CMV/pp65-specific T cell clonotypes, including the inhibitory receptor LILRB1. Interestingly, T cell clonotypes of high-avidity showed higher LILRB1 expression than the low-avidity ones and LILRB1 blockade moderately increased T cell proliferation. Similar findings were made for CD8 T cell repertoires specific for the CMV/IE-1 epitope. There was a gradual in vivo loss of high-avidity T cells with time for both CMV specificities, corresponding to virus-specific CD8 T cells expressing enhanced LILRB1 levels. In sharp contrast, the EBV/BMFL1-specific T cell clonal composition and distribution, once established, displayed an exceptional stability, unrelated to TCR-pMHC binding avidity or LILRB1 expression.

Conclusions

These findings reveal an overall long-term avidity decline of CMV- but not EBV-specific T cell clonal repertoires, highlighting the differing role played by TCR-ligand avidity over the course of these two latent herpesvirus infections. Our data further suggest that the inhibitor receptor LILRB1 potentially restricts the clonal expansion of high-avidity CMV-specific T cell clonotypes during latent infection. We propose that the mechanisms regulating the long-term outcome of CMV- and EBV-specific memory CD8 T cell clonotypes in humans are distinct.
Genomic insights into the adaptation of Synechococcus to the coastal environment on Xiamen
Authors: Zhang Ting , Zhou Kun , Wang Yanhui , Xu Jinxin , Zheng Qiang , Luo Tingwei , Jiao Nianzhi
Published: November 2023

Synechococcus are widely distributed in the global ocean, from the pelagic zone to coastal waters. However, little is known about Synechococcus in coastal seawater due to limitations in isolation and culture conditions. In this study, a combination of metagenomic sequencing technology, flow cytometry sorting, and multiple displacement amplification was used to investigate Synechococcus in the coastal seawater of Xiamen Island. The results revealed 18 clades of Synechococcus and diverse metabolic genes that appear to contribute to their adaptation to the coastal environment. Intriguingly, some metabolic genes related to the metabolism of carbohydrates, energy, nucleotides, and amino acids were found in 89 prophage regions that were detected in 16,258 Synechococcus sequences. The detected metabolic genes can enable prophages to contribute to the adaptation of Synechococcus hosts to the coastal marine environment. The detection of prophages also suggests that the cyanophages have infected Synechococcus. On the other hand, the identification of 773 genes associated with antiviral defense systems indicates that Synechococcus in Xiamen have evolved genetic traits in response to cyanophage infection. Studying the community diversity and functional genes of Synechococcus provides insights into their role in environmental adaptation and marine ecosystems.
Formation of two-dimensional laser-induced periodic surface structures on titanium by GHz burst mode femtosecond laser pulses
Authors: Kawabata Shota , Bai Shi , Obata Kotaro , Ozasa Kazunari , Miyaji Godai , Sugioka Koji
Published: November 2023

GHz burst mode femtosecond (fs) laser pulses, which consist of a series of pulse trains with ultra-fast intervals of several hundred picoseconds, have offered distinct features for material processing compared to conventional irradiation of laser pulses (single-pulse mode). We apply GHz burst mode processing to fabricate laser-induced periodic surface structures (LIPSS) on the material surfaces. In our previous work for silicon (Si), we have found that GHz burst mode can create unique two-dimensional (2D) LIPSS composed of both parallel and perpendicular to the laser polarization direction. We proposed that the formation of 2D-LIPSS is attributed to the synergetic contributions of electromagnetic and hydrodynamic mechanisms. To further investigate more detailed formation mechanisms and explore practical applications, we employ titanium (Ti), whose properties are significantly different from Si. We demonstrate that GHz burst mode fs laser pulses (central wavelength: 1,030 nm, intra-pulse width: 230 fs, intra-pulse repetition rate (an intra-pulse interval): 4.88 GHz (205 ps) and burst pulse repetition rate: 10 kHz) can also fabricate 2D-LIPSS on Ti surfaces. We attribute the dominant formation mechanism of 2D-LIPSS to the generation of hot spots with highly enhanced electric fields due to transient change of material properties during GHz burst pulse irradiation. Based on this speculation, properly tailoring the shapes of the burst pulse with an optimum intra-pulse number enables the creation of well-defined 2D-LIPSS. Furthermore, essentially homogeneous 2D-LIPSS can be formed in a large area by laser scanning of a focused fs laser beam with a stage scanning speed of 5 mm/s.
Congenital scrub typhus: a case report and literature review
Authors: Liang Pinghua , Su Zengling , Chen Min , Li Sitao
Published: November 2023

Background

This study aimed to analyze the clinical course of a newborn with congenital scrub typhus caused by vertical transmission and explore early diagnosis and treatment strategies. The clinical data of the neonate were retrospectively analyzed and the related literature was reviewed.

Case presentation

The newborn was a full-term one, with a good Apgar score at birth. The neonate had apnea at 3 h of life, requiring NICU care and IV antibiotics (piperacillin) for suspected sepsis. An examination revealed hepatosplenomegaly. Blood tests revealed anemia and thrombocytopenia and a chest x-ray showed patchy inflammation. On the second day of life, he developed a fever. On the third day of life, he required mechanical ventilation because his condition worsened after he presented with dyspnea, hypotension, depressed sensorium, and other signs of sepsis. Importantly, the neonate's mother had a history of scrub typhus at 31+ weeks of gestation. While the blood culture result was still pending, high-throughput sequencing of blood and cerebrospinal fluid was performed. To address the suspected scrub typhus infection, oral azithromycin dry suspension was added to the treatment regimen. High-throughput sequencing results on the 5th day of life confirmed a significant presence of 16SrRNA sequences in the blood, suggesting an Orientia tsutsugamushi infection. The neonate steadily recovered and was discharged 16 days after hospitalization. The neonate was followed up for 9 months, and the outcome was favorable with normal growth and development.

Conclusions

This article reports a case of congenital Orientia tsutsugamushi infection, a rare condition caused by vertical transmission. Our review of the literature, combined with the presented case, brings the total number of documented congenital scrub typhus cases caused by vertical transmission to eight. Regrettably, one patient from this group unexpectedly died on the 10th day of hospitalization, resulting in a mortality rate of 12.5% (1/8). The special transmission mode and clinical manifestations of this disease will serve as an alert to doctors for timely diagnosis and treatment. Because of the non-specific clinical manifestations of congenital scrub typhus, limited understanding, low index of suspicion among clinicians, and a lack of diagnostic facilities, scrub typhus is seriously underdiagnosed in pregnant women, fetuses, and neonates.
Development and validation of a disulfidptosis-related scoring system to predict clinical outcome and immunotherapy response in acute myeloid leukemia by integrated analysis of single-cell and bulk RNA-sequencing
Authors: Zhong Fangmin , Jiang Junyao , Yao Fang-Yi , Liu Jing , Shuai Xu , Wang Xin-Lu , Huang Bo , Wang Xiaozhong
Published: November 2023

Background: Disulfidptosis is a metabolically relevant mode of cell death, and its relationship with acute myeloid leukemia (AML) has not been clarified. In this study, disulfidptosis scores were computed to examine the potential biological mechanisms.

Methods: Consensus clustering was applied to detect disulfidptosis-related molecular subtypes. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a DRG prognostic model.

Results: DRGs are upregulated in AML and associated with poor prognosis. The higher the disulfidptosis activity score, the worse the clinical outcome for patients, accompanied by increased immune checkpoint expression and tumor marker pathway activity. The two molecular subtypes exhibited distinct prognoses and tumor microenvironment (TME) profiles. A prognostic risk score model was established using six DRGs, and the AML cohort was divided into high- and low-risk score groups. Patients in the high-risk group experienced significantly worse prognosis, which was validated in seven AML cohorts. Receiver Operating Characteristic (ROC) curve analysis indicated that the area under the curve values for risk score prediction of 1-, 3-, and 5-year survival were 0.779, 0.714, and 0.778, respectively. The nomogram, in conjunction with clinicopathological factors, further improved the accuracy of prognosis prediction. The high-risk score group exhibited a higher somatic mutation frequency, increased immune-related signaling pathway activity, and greater immune checkpoint expression, suggesting a certain degree of immunosuppression. Patients with advanced age and higher cytogenetic risk also had elevated risk scores. According to drug prediction and AML anti-PD-1 therapy cohort analysis, the low-risk score group displayed greater sensitivity to chemotherapy drugs like cytarabine and midostaurin, while the high-risk score group was more responsive to anti-PD-1 therapy. Finally, clinical samples were collected for sequencing analysis, confirming that the progression of myeloid leukemia was associated with a higher risk score and a negative disulfidptosis score, suggesting that the poor prognosis of AML may be associated with disulfidptosis resistance.

Conclusion: In conclusion, a systematic analysis of DRGs can help to identify potential disulfidptosis-related mechanisms and provide effective new biomarkers for prognosis prediction, TME assessment, and the establishment of personalized treatment plans in AML.
Integrating bulk and single-cell RNA sequencing data reveals epithelial-mesenchymal transition molecular subtype and signature to predict prognosis, immunotherapy efficacy, and drug candidates in low-grade gliomas
Authors: Wang Chengcheng , He Zheng
Published: November 2023

Objective: Epithelial-mesenchymal transition (EMT) is a tightly regulated and dynamic process occurring in both embryonic development and tumor progression. Our study aimed to comprehensively explore the molecular subtypes, immune landscape, and prognostic signature based on EMT-related genes in low-grade gliomas (LGG) in order to facilitate treatment decision-making and drug discovery.

Methods: We curated EMT-related genes and performed molecular subtyping with consensus clustering algorithm to determine EMT expression patterns in LGG. The infiltration level of diverse immune cell subsets was evaluated by implementing the single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms. The distinctions in clinical characteristics, mutation landscape, and immune tumor microenvironment (TME) among the subtypes were subjected to further investigation. Gene Set Variation Analysis (GSVA) was performed to explore the biological pathways that were involved in subtypes. The chemo drug sensitivity and immunotherapy of subtypes were estimated through GDSC database and NTP algorithm. To detect EMT subtype-related prognostic gene modules, the analysis of weighted gene co-expression network (WGCNA) was performed. The LASSO algorithm was utilized to construct a prognostic risk model, and its efficacy was verified through an independent CGGA dataset. Finally, the expression of the hub genes from the prognostic model was evaluated through the single-cell dataset and in-vitro experiment.

Results: The TCGA-LGG dataset revealed the creation of two molecular subtypes that presented different prognoses, clinical implications, TME, mutation landscapes, chemotherapy, and immunotherapy. A three-gene signature (SLC39A1, CTSA and CLIC1) based on EMT expression pattern were established through WGCNA analysis. Low-risk patients showed a positive outlook, increased immune cell presence, and higher expression of immune checkpoint proteins. In addition, several promising drugs, including birinapant, fluvastatin, clofarabine, dasatinib, tanespimycin, TAK−733, GDC−0152, AZD8330, trametinib and ingenol-mebutate had great potential to the treatment of high risk patients. Finally, CTSA and CLIC1 were highly expressed in monocyte cell through single-cell RNA sequencing analysis.

Conclusion: Our research revealed non-negligible role of EMT in the TME diversity and complexity of LGG. A prognostic signature may contribute to the personalized treatment and prognostic determination.
Comparing CNNs and PLSr for estimating wheat organs biophysical variables using proximal sensing
Authors: Carlier Alexis , Dandrifosse Sébastien , Dumont Benjamin , Mercatoris Benoit
Published: November 2023

Estimation of biophysical vegetation variables is of interest for diverse applications, such as monitoring of crop growth and health or yield prediction. However, remote estimation of these variables remains challenging due to the inherent complexity of plant architecture, biology and surrounding environment, and the need for features engineering. Recent advancements in deep learning, particularly convolutional neural networks (CNN), offer promising solutions to address this challenge. Unfortunately, the limited availability of labeled data has hindered the exploration of CNNs for regression tasks, especially in the frame of crop phenotyping. In this study, the effectiveness of various CNN models in predicting wheat dry matter, nitrogen uptake, and nitrogen concentration from RGB and multispectral images taken from tillering to maturity was examined. To overcome the scarcity of labeled data, a training pipeline was devised. This pipeline involves transfer learning, pseudo-labeling of unlabeled data and temporal relationship correction. The results demonstrated that CNN models significantly benefit from the pseudolabeling method, while the machine learning approach employing a PLSr did not show comparable performance. Among the models evaluated, EfficientNetB4 achieved the highest accuracy for predicting above-ground biomass, with an R² value of 0.92. In contrast, Resnet50 demonstrated superior performance in predicting LAI, nitrogen uptake, and nitrogen concentration, with R² values of 0.82, 0.73, and 0.80, respectively. Moreover, the study explored multi-output models to predict the distribution of dry matter and nitrogen uptake between stem, inferior leaves, flag leaf, and ear. The findings indicate that CNNs hold promise as accessible and promising tools for phenotyping quantitative biophysical variables of crops. However, further research is required to harness their full potential.
Transitions in sense of coherence among middle-aged women raising adolescents before and during the COVID-19 pandemic
Authors: Omiya Tomoko , Sankai Tomoko , Miyazaki Akari , Abe Yoshiki , Deguchi Naoko Kumada
Published: November 2023

Objective

A longitudinal study was conducted among Japanese women raising adolescents to determine how the COVID-19 pandemic has affected their sense of coherence (SOC) and to provide suggestions for supporting them.

Methods

The SOC scores of 138 pairs of middle-aged women and their children (junior high school students) were compared at two time points: 2019 (before the pandemic, T1) and 2020 (during the pandemic, T2).

Results

Overall, the women’s SOC did not change, whereas the adolescents’ SOC increased. In contrast, 44% of the women’s SOC scores decreased during the pandemic; no differences were detected between the SOC maintenance and increase group (G1) and the SOC decrease group (G2) in mental health, subjective physical health, social capital, and job status, and the child variables were not related. Multiple regression analysis of G1 and G2 with SOC at T2 as the dependent variable showed that for G2, at T1, having good mental and physical health conditions, a rich social capital, and having a job were positively associated with SOC during the pandemic.

Conclusion

Middle-aged Japanese women, who often work as informal workers, are easily laid off and are involved in care work. Thus, the change in their socioeconomic status due to the pandemic may have been severe. Given the long-term social impact of the pandemic, it is necessary to consider support for women, including economic and social support such as employment and building human connections.
Self-pacing ameliorates recall deficit when listening to vocoded discourse: a cochlear implant simulation
Authors: Hansen Thomas A. , O’Leary Ryan M. , Svirsky Mario A. , Wingfield Arthur
Published: November 2023

Introduction

In spite of its apparent ease, comprehension of spoken discourse represents a complex linguistic and cognitive operation. The difficulty of such an operation can increase when the speech is degraded, as is the case with cochlear implant users. However, the additional challenges imposed by degraded speech may be mitigated to some extent by the linguistic context and pace of presentation.

Methods

An experiment is reported in which young adults with age-normal hearing recalled discourse passages heard with clear speech or with noise-band vocoding used to simulate the sound of speech produced by a cochlear implant. Passages were varied in inter-word predictability and presented either without interruption or in a self-pacing format that allowed the listener to control the rate at which the information was delivered.

Results

Results showed that discourse heard with clear speech was better recalled than discourse heard with vocoded speech, discourse with a higher average inter-word predictability was better recalled than discourse with a lower average inter-word predictability, and self-paced passages were recalled better than those heard without interruption. Of special interest was the semantic hierarchy effect: the tendency for listeners to show better recall for main ideas than mid-level information or detail from a passage as an index of listeners’ ability to understand the meaning of a passage. The data revealed a significant effect of inter-word predictability, in that passages with lower predictability had an attenuated semantic hierarchy effect relative to higher-predictability passages.

Discussion

Results are discussed in terms of broadening cochlear implant outcome measures beyond current clinical measures that focus on single-word and sentence repetition.
The influence of single-session reward-based attentional bias modification on attentional biases towards threat as measured by the N2pc component
Authors: Kang Susan , Osinsky Roman
Published: November 2023

Attentional biases toward threatening faces have repeatedly been studied in the context of social anxiety, with etiological theories suggesting exacerbated biases as a possible cause for the latter. To counteract these postulated effects, research has focused on the concept of attentional bias manipulation (ABM), in which spatial contingencies between succeeding stimuli are traditionally employed in training paradigms designed to deliberately shift automatic attention processes away from threat-related stimuli. The ABM research field has been faced with various methodological challenges, such as inconsistent results, low reliabilities of dependent variables and a high susceptibility to moderating factors. We aimed to combine several recent approaches to address these issues. Drawing upon theories of value-driven attention, we explored reward-based contingencies in a Dot Probe task to improve the training’s efficacy, combined with neurophysiological measures for greater reliability compared to reaction times, while evaluating the moderating effect of explicitness in the instruction. In a healthy sample (N = 60) and within a single session, we found a general attentional bias toward angry faces present across all conditions as indicated by the N2pc, which was, however, marked by large intrinsic lateralization effects, with submeasures exhibiting opposing polarities. This prompted us to explore an alternative, intrahemispheric calculation method. The new N2pc variant showed the attentional bias to have disappeared at the end of the training session within the explicit instruction group. Reliabilities of the main dependent variables were varied from excellent to questionable, which, together with the exploratory nature of the analysis, leaves this result as preliminary.
A socio-ecological model of factors influencing physical activity in pregnant women: a systematic review
Authors: Sun Junjiang , Piernicka Magdalena , Worska Aneta , Szumilewicz Anna
Published: November 2023

Physical activity (PA) is safe for most pregnant women, improving both maternal fitness and birth outcomes. Despite evidence of benefits, most pregnant women eliminate or reduce PA during pregnancy. This systematic review aimed to analyze the factors affecting maternal PA during pregnancy with reference to a socio-ecological model. A systematic search of relevant published studies between 2001 and 2022 was conducted through PubMed, Scopus, Web of Science, Academic Search Ultimate, Medline, and SPORTDiscus with full text via the EBSCO platform. A total of 32 studies that met the inclusion criteria were reviewed. The findings revealed that various study designs can lead to different outcomes in terms of what is identified as a PA facilitator or barrier. The factors that positively influenced PA in pregnant women were: higher levels of education, knowledge, and skills, as well as access to mass media. Conversely, lower levels of education, lack of knowledge and skills, low income, pregnancy discomforts, limited time, safety concerns, and societal perceptions of PA in pregnancy acted as barriers. Additionally, family, colleagues/friends, and partners could either support or hinder PA. Factors affecting overall maternal PA were somewhat different from those affecting the moderate-to-vigorous intensity of PA. Pregnant women receive little organizational and policy support. There is an urgent need to provide accessible information and resource systems for pregnant women. Since most pregnant women are motivated to engage in PA and susceptible to family advice, interventions should not be limited only to pregnant women, but should involve a family member, especially partners. There is a need to take global, systemic actions to promote an active lifestyle in pregnancy. Addressing safety concerns related to PA during pregnancy should be a significant part of these promotional activities.
Effects of environmental and genetic interactions on job burnout in coal miners: interactions between occupational stress, coping styles, and NR3C2 gene polymorphisms
Authors: Lin Xin , Ma Xiaofan , Yi Xiaoting , Qu Chao , Li Fuye
Published: November 2023

Objectives

To investigate the current situation regarding occupational burnout among coal miners, explore the relationship between NR3C2 gene polymorphism and occupational burnout, and analyze the influence of the interaction between environment and gene on occupational burnout. This study provides a scientific basis for formulating health strategies to combat job burnout.

Methods

A total of 1,500 first-line coal mine workers were selected by cluster random sampling, and the job burnout scale, job content questionnaire (JCQ), and simplified coping style questionnaire (SCSQ) were used for the questionnaire survey. A total of 150 workers were randomly selected from the high burnout group and the low burnout group, and a total of 300 workers were selected as the research objects to examine the relationship between gene polymorphism, environment-gene interactions and burnout. This study employed iMLDRTM genotyping technology for NR3C2 gene (rs5522, rs2070950) polymorphism analysis. The relationship between the occurrence of job burnout, occupational stress, coping styles and the NR3C2 gene was analyzed.

Results

Finally, a total of 1,282 valid questionnaires were retrieved, with an effective recovery rate of 85.5%. The study included 128 participants (10%) with zero burnout, 400 (31.2%) with mild burnout, 649 (50.6%) with moderate burnout and 105 (8.2%) with severe burnout. There were significant differences in the rate of burnout among miners with respect to sex, age, working years, educational level, shifts, and marital status (P < 0.05). The difference in occupational stress between the different job burnout groups was statistically significant (P < 0.05). Compared with the GG genotype of rs2070950 of the NR3C2 gene, the CC genotype was identified as a susceptibility gene for occupational burnout (P < 0.05). In respect to rs5522, rs2070950, occupational stress, positive coping, and negative coping, the low-risk group was unlikely to suffer from job burnout compared with the high-risk group (OR = 0.103, 95%CI: 0.058–0.182).

Conclusion

In addition to demographic characteristics, occupational stress and negative coping styles were also identified as risk factors for job burnout. The interaction between locus rs5522, locus rs2070950, occupational stress, positive response, and negative response were found to affect the incidence of occupational burnout.
Occupational exposure and health surveys at metal additive manufacturing facilities
Authors: Assenhöj Maria , Almstrand Ann-Charlotte , Kokelj Spela , Ljunggren Stefan A. , Olin Anna-Carin , Karlsson Helen
Published: November 2023

Introduction

Additive manufacturing is a novel state-of-the art technology with significant economic and practical advantages, including the ability to produce complex structures on demand while reducing the need of stocking materials and products. Additive manufacturing is a technology that is here to stay; however, new technologies bring new challenges, not only technical but also from an occupational health and safety perspective. Herein, leading Swedish companies using metal additive manufacturing were studied with the aim of investigating occupational exposure and the utility of chosen exposure- and clinical markers as predictors of potential exposure-related health risks.

Methods

Exposure levels were investigated by analysis of airborne dust and metals, alongside particle counting instruments measuring airborne particles in the range of 10 nm−10 μm to identify dusty work tasks. Health examinations were performed on a total of 48 additive manufacturing workers and 39 controls. All participants completed a questionnaire, underwent spirometry, and blood and urine sampling. A subset underwent further lung function tests.

Results

Exposure to inhalable dust and metals were low, but particle counting instruments identified specific work tasks with high particle emissions. Examined health parameters were well within reference values on a group level. However, statistical analysis implied an impact on workers kidney function and possible airway inflammation.

Conclusion

The methodology was successful for investigating exposure-related health risks in additive manufacturing. However, most participants have been working <5 years. Therefore, long-term studies are needed before we can conclusively accept or reject the observed effects on health.
A comparison of two methods for moving through a virtual environment: walking in place and interactive redirected walking
Authors: Banakou Domna , Slater Mel
Published: November 2023

Moving through a virtual environment that is larger than the physical space in which the participant operates has been a challenge since the early days of virtual reality. Many different methods have been proposed, such as joystick-based navigation, walking in place where the participant makes walking movements but is stationary in the physical space, and redirected walking where the environment is surreptitiously changed giving the illusion of walking in a long straight line in the virtual space but maybe a circle in the physical space. Each type of method has its limitations, ranging from simulator sickness to still requiring more physical space than is available. Stimulated by the COVID-19 lockdown, we developed a new method of locomotion which we refer to as interactive redirected walking. Here, the participant really walks but, when reaching a boundary, rotates the virtual world so that continuation of walking is always within the physical boundary. We carried out an exploratory study to compare this method with walking in place with respect to presence using questionnaires as well as qualitative responses based on comments written by the participants that were subjected to sentiment analysis. Surprisingly, we found that smaller physical boundaries favor interactive redirected walking, but for boundary lengths more than approximately 7 adult paces, the walking-in-place method is preferable.