bluuebunny/crossref_metadata_2025 huggingface dataset:
SELF-DESTRUCTION THROUGH GREED: “THE QUEEN OF SPADES” AND “ALI BABA AND FORTY THIEVES”
Authors: Kara Mustafa
Published: September 2024

Greed, a cardinal sin originating from early Christianity, is a notable recurring theme in literature and is universally prevalent throughout civilizations, literary works, and theological systems. It is widely held that people who exhibit greed defy God's command and face punishment, but those who sincerely abide by His commands receive blessings. The works The Queen of Spades by Alexandr Pushkin and The Tale of Ali Baba and the Forty Thieves in The Thousand and One Nights, belong to separate literary traditions. However, both stories depict antagonistic individuals who ultimately meet their own end as a result of their greedy behaviour. In these literary works, there are two different sets of characters, the rewarded and the punished. Within these literary pieces, the initial set of characters experiences significant consequences for their actions, whilst the subsequent group is duly compensated. These works demonstrate that specific topics surpass the limitations of time and culture, regardless of the differences between the eras and communities in which they originated. Accordingly, this study aims to reveal how greed turns into a way of self-destruction in these two works, which belong to completely different periods and geographies, through textual analysis.
Uma metrópole em formação nas Guianas? A conurbação Caiena-Kourou na Guiana Francesa
Authors: Stéphane Granger
Published: September 2024

A metropolização é a forma mais concluída do atual processo de urbanização, com a concentração de populações, atividades de comando e capitais em algumas grandes cidades estendendo-se pela inclusão de municípios periféricos cada vez mais afastados. Na França, as métropoles constituem uma nova entidade administrativa urbana com essas caractérísticas, mas com um escalão bem menor. Na Guiana Francesa, a junção das áreas urbanas de Caiena, a capital administrativa, e de Kourou, a capital e a sede da indústria espacial da União Europeia, está criando uma zona urbana ligada por solidariedades e fluxos de mobilidade, enquanto ao mesmo tempo essa concentra os dois terços da população franco-guianense e a quasi-totalidade dos empregos e empresas, e um monopólio nas funções avançadas e de comando. Porém, se a conurbação Caiena-Kourou chega a um ponto de constituir uma metrópole à escala da pouco povoada Guiana Francesa, ainda está longe de ter um papel internacional ao qual poderia pretender devido à sua situação de interface entre Caribe, América do Sul e Europa. De fato, mais parece uma margem da França e da União Europeia, enquanto contribue ao desequilíbrio demográfico e econômico deste território francês da América do Sul.
A Comparative Study of Machine Learning Models for Sentiment Analysis of Dana App Reviews
Authors: Sujana Yudianto
Published: September 2024

Sentiment analysis of user reviews has become increasingly important for mobile app developers, as it can provide valuable insights into customer satisfaction and guide the improvement of app features. In this study, we compared the performance of three machine learning models - Support Vector Machine, Neural Network, and Bidirectional Long Short-Term Memory - in classifying the sentiment of user reviews for the Dana mobile application. Our results showed that the Bi-LSTM model outperformed the other models, achieving the highest accuracy, precision, recall, and F1-score. The superior performance of the Bi-LSTM model can be attributed to its ability to capture long-term dependencies and contextual information within the review text, which is crucial for accurate sentiment analysis. These findings highlight the effectiveness of deep learning techniques in handling the complexities of language and sentiment analysis, particularly in the context of user-generated content. The insights from this study can inform the development of more accurate and efficient sentiment analysis tools for mobile app reviews, ultimately benefiting both app developers and users.
The Moderating Effect of Role Conflict on the Relationship between Perceived Organizational Support and Work Engagement
Authors: Yılmaz Fatma
Published: September 2024

The purpose of the study is to investigate how role conflict affects the relationship between work engagement and perceived organizational support. The emotional and practical support that workers feel they receive from their organizations is referred to as perceived organizational support. Work engagement is the term used to describe a person's dedication, loyalty, and commitment to their work. The emergence of competing demands that people encounter in their professional responsibilities is referred to as role conflict. A questionnaire-based approach is used to collect data from 299 workers in a public agency. The acquired data is then subjected to statistical analysis using the AMOS and SPSS 24 software programs. The results imply that work engagement and perceived organizational support are positively correlated. Moreover, it is discovered that role conflict moderated the association between work engagement and perceived organizational support.
Step-by-step: A clinical pathway for stepped care management of fear of cancer recurrence– results of a three round online Delphi consensus process with Australian health professionals and researchers
Authors: Smith Allan 'Ben' , Girgis Afaf , Taylor Natalie , Pearce Alison , Liu Jia , Shepherd Heather L. , Wu Verena S. , Garvey Gail , Kirsten Laura , Zakhary Iman , Ee Carolyn , Ewald Daniel , Miller Annie , Shaw Joanne
Published: September 2024

Purpose
Fear of cancer recurrence (FCR) is not routinely addressed in clinical practice, meaning many cancer survivors forego effective interventions. We established expert consensus on a clinical pathway to help health professionals identify and manage FCR.
Methods
Australian health professionals and researchers working with adult cancer survivors participated in a 3-round Delphi study promoted via oncology professional bodies and social media. The Round 1 online survey presented 38 items regarding FCR screening, triage, assessment, referral, and stepped care, based on a literature review, related pathways/guidelines, and expert input. Participants rated how representative of best-practice items were on a 5-point scale (strongly disagree – strongly agree), with optional qualitative feedback. Consensus was defined as ≥80% of participants strongly/agreeing with items. Items not reaching consensus were re-presented in two subsequent rounds with new items, derived from content analysis of qualitative feedback.
Results
From 94 participants in Round 1 (89% health professionals) 26/38 (68%) items reached consensus. By round 3, 35/38 (92%) items, including 8 new items, reached consensus. Routine FCR screening and triage conversations, and stepped care management were endorsed. However, timing of FCR screening/triage did not reach consensus.
Conclusions
This world-first FCR clinical pathway incorporating contemporary evidence and expert opinion recommends routine screening and triage to stepped care management of FCR. Some pathway components, such as screening or triage timing, may need tailoring for different contexts.
Implications for Cancer Survivors
Implementation of the pathway could aid routine identification and management of FCR, reducing its burden on cancer survivors and the healthcare system.
First detection of V410L kdr mutation in Aedes aegypti populations of Argentina and its correlation with the toxicological evidence
Authors: Gonzalez Paula V. , Loureiro Aline C. , Gómez-Bravo Andrea , Castillo Paola , Espinosa Manuel , Gil José F. , Martins Ademir J , Harburguer Laura V.
Published: September 2024

BACKGROUND
Aedes aegypti (L.) is the main vector of dengue, yellow fever, Zika and chikungunya viruses in many parts of the world impacting millions of people worldwide each year. Insecticide-based interventions have been effective in controlling Aedes mosquito populations for several years, but in recent times, resistance to these compounds has developed, posing a global threat to the control of this mosquito.
METHODS
Ovitraps were used to collect A. aegypti eggs in the cities of Tartagal and San Ramón de la Nueva Orán (Salta), Puerto Iguazú (Misiones) and Clorinda (Formosa). WHO impregnated papers with the discriminating concentration (DC) of permethrin, 5X, 10X and pirimiphos methyl were used for the toxicological bioassays. We also genotyped each sample for the three kdr single nucleotide polymorphisms (SNP): V410L, V1016I and F1534C in individual TaqMan qPCR reactions.
RESULTS
All investigated A. aegypti populations were highly resistant to permethrin, as the mortality percentage with the permethrin 10XDC remained below 98%. However, all populations were 100% susceptible to pirimiphos-methyl. Kdr genotyping demonstrated the presence of the V410L mutation for the first time in Argentina in all the populations studied. A prevalence of the triple mutant genotype (LL + II + CC) was observed in the northeastern cities of Clorinda (83.3%) and Puerto Iguazú (55.6%).
CONCLUSIONS
This study demonstrates for the first time the presence and intensity of resistance to permethrin in different populations from Argentina, and correlates the observed phenotype with the presence of kdr mutations (genotype).
The intelligent Diabetes TelemonitoRing Using decision Support to treat patients on insulin Therapy (DiaTRUST) trial: study protocol for a randomized controlled trial
Authors: Thomsen Camilla H. N. , Nørlev Jannie D. , Hangaard Stine , Jensen Morten H. , Hejlesen Ole , Kristensen Sika N. S. , Aradóttir Tinna B. , Kaas Anne , Vestergaard Peter , Kronborg Thomas
Published: September 2024

Background
Diabetes affects 10.5% of adults globally, with type 2 diabetes accounting for 90–95% of cases. Achieving optimal glycemic control is crucial yet challenging, particularly with insulin therapy, where 30–50% of patients fail to meet treatment targets. Telemedicine can improve diabetes management but generates vast amounts of data, burdening healthcare providers. Integrating clinical decision support tools into telemonitoring systems may enhance care efficiency and glycemic control.
Methods
The trial is a six-month, three-arm, open-label randomized controlled study conducted at Steno Diabetes Center North Denmark, aiming to enroll 51 participants with type 2 diabetes on insulin therapy. Participants will be divided in a 3:1:1 ratio into telemonitoring with decision support, telemonitoring without decision support, and usual care groups. The study employs connected insulin pens, continuous glucose monitors (CGMs), and activity trackers to enable telemonitoring. Outcomes measured include CGM time in range, HbA1c, hypoglycemia and hyperglycemia incidents, total daily insulin dose, body weight, treatment satisfaction, and adherence.
Discussion
Telemonitoring with decision support has the potential to revolutionize diabetes management by offering personalized treatment suggestions, thereby reducing the burden on healthcare providers and improving patient outcomes. This study will provide valuable insights into the effectiveness of such an approach in achieving glycemic control in people with type 2 diabetes on insulin therapy. By evaluating both clinical outcomes and patient and healthcare providers’ satisfaction, the study aims to contribute to the development of efficient, scalable telehealth solutions for diabetes care.
Trial Registration:
The trial is registered with ClinicalTrials.gov (NCT06185296) on December 14, 2023.
CD137L promotes immune surveillance in melanoma via HLTF regulation
Authors: Liu Hong , Liang Long , Zhu Lin , Li Xin , Zhang Guan Xiong , Kuang Xinwei , Hung Mien-Chie , Liu Jing , Chen Xiang
Published: September 2024

Immune checkpoint blockers (ICBs) have shown considerable effect in a number of malignancies. However, only limited patients were responsive to ICBs. Therefore, it is critical to explore novel therapeutic target. Herein, by integrating multi-omics data, ICB treating melanoma patient cohort, we identified that tumor CD137L is positively correlated with efficacy of PD-1 blockade in melanoma patient cohorts. Functionally, we showed that induction of CD137L in cancer cells significantly enhanced anti-tumor immunity by facilitated CD8+ T cell survival both in vivo and in vitro. Mechanistically, we found that helicase-like transcription factor (HLTF) functioned as the key transcriptional regulator controlling CD137L expression via phosphorylation of serine at position 398. Therapeutically, we identified a FDA-approved drug, AICAR (acadesine), functioned as a CD137L specific agonist, showed combination effect with PD-1 blockade or CTLA4 blockade. Taken together, our study reveals HLTF-mediated regulatory mechanism controlling CD137L expression, potential predictor for assessing the efficacy of anti-PD-1 therapy in clinic, develop a novel combination therapy to enhance the efficacy of ICBs in melanoma.
Physiological provocation compared to acetazolamide in the assessment of cerebral hemodynamics – A case report
Authors: Henriksen Alexander Cuculiza , Thomsen Gerda Krog , Knudsen Gitte M , Stavngaard Trine , Rosenbaum Sverre , Marner Lisbeth
Published: September 2024

Background: Severe large vessel disease may lead to cerebral hemodynamic failure that critically impairs cerebral blood flow (CBF) regulation elevating the risk of ischemic events. Assessment of the condition is often based on changes in CBF during vasodilatation; however, pharmacologically induced vasodilation does not reflect the physiological condition during an ischemic event caused by hemodynamic failure. We compared a [15O]H2O PET brain scan during vasodilation to a [99mTc]HMPAO SPECT brain scan during an ongoing transient ischemic attack (TIA).
Case presentation: A single patient presenting with limb-shaking TIA underwent CT, Digital Subtraction Angiography, and two cerebral perfusion scans: [15O]H2O PET and [99mTc]HMPAO SPECT. Acetazolamide was used in the PET scan to induce vasodilatation, and during the SPECT scan physiological stress, standing up rapidly, was used to induce limb-shaking TIA.
CT-angiography and Digital Subtraction Angiography demonstrated an occluded anterior cerebral artery distal to the circle of Willis on the left side, with a corresponding infarction in the watershed area. Collaterals supplied the main vascular territory of the anterior cerebral artery. During rest, neither perfusion scans demonstrated reduced perfusion outside of the ischemic core. However, we found a pronounced difference between the PET utilizing acetazolamide and the SPECT during the TIA. The PET scan demonstrated a reduced CBF in vascular territory supplied by collaterals, while the area around the ischemic core was not affected. Contrary, the SPECT had only a minor decrease in the collateral-supplied area, whereas the watershed area proximal to the infarct core had a pronounced decrease.
Conclusions: The observed discrepancy in compromised areas during physiological provocation compared to pharmacological induced vasodilation questions the use of an unphysiological stressor for assessment of cerebrovascular hemodynamics. A physiological provocation test may achieve more clinically relevant evaluation.
Exploring the Causal Effect of Dietary Factors on Hemorrhoids: A Two-Sample Mendelian Randomization Study
Authors: Hu Zongju , Zhao Zongxian , Yao Yuan , Su Xinyu , Zhu Shu , Zhang Jun
Published: September 2024

Background
Previous research has found that dietary factors are closely associated with the risk of hemorrhoids. Modifying dietary structure and offering evidence-based dietary guidance are crucial for preventing and managing hemorrhoids disease. Our study aims to investigate the causal effects of 17 dietary factors on the risk of hemorrhoids using a two-sample mendelian randomization (MR) approach.
Method
Genetic variants and instrumental variables for dietary factors (exposure datasets) were obtained from UK Biobank (UKB), and hemorrhoids (outcome datasets) related single-nucleotide polymorphisms (SNPs) were extracted from the European Bioinformatics Institute (EBI). Eligible SNPs were selected for subsequent MR analysis and the Inverse Variance Weighted (IVW) method served as the primary analytical approach. Finally, we conducted sensitivity analyses and heterogeneity tests on the MR results
Result
Our findings indicated that vegetables (OR: 0.591, 95% CI: 0.428–0.817, p = 0.010) and fruits (OR: 0.764, 95% CI: 0.639–0.915, p = 0.005) intake has a protective effect, while alcohol intake (OR: 1.588, 95% CI: 1.246–2.024, p < 0.001), processed meat (OR: 1.307, 95% CI: 1.077–1.585, p = 0.007), oily fish (OR: 1.119, 95% CI: 1.014–1.235, p = 0.025), and cereal (OR: 1.209, 95% CI: 1.036–1.411, p = 0.016) intake have been identified as risk factors for hemorrhoids. Indeed, the causal relationships between above dietary factors and hemorrhoids were robust under the MR pleiotropy residual sum and outlier (MR-PRESSO) test and heterogeneity test.
Conclusions
This study offers scientific dietary guidance for patients and aims to decrease the incidence of hemorrhoids by elucidating the specific effects of dietary factors.
High Diagnostic Performance of 68Ga-FAPI-based Techniques in Female Cancer Detection: Systematic Review and Meta-Analysis
Authors: Gabdullina Madina , Ainakulova Akmaral , Elboga Umut , Karibayeva Indira , Alisherov Galymzhan , Zhakenova Zhanar , Amankulov Jandos , Zholdybay Zhamilya
Published: September 2024

Positron emission tomography (PET) imaging techniques combined with computed tomography (PET/CT) or magnetic-resonance imaging (PET/MRI) have been developed in the last decades to improve primary diagnosis, staging, restaging, planning radiotherapy, and assessment of therapy efficacy for cancer patients. Currently, the most widely recognized and well-studied radiopharmaceutical is 2-deoxy-2[18F]fluoro-D-glucose ([18F]-FDG). However, [18F]-FDG has some limitations related to physiological accumulation in various organs and low avidity for some histological subtypes. Interest in Gallium 68 ([68Ga])-labeled fibroblast activation protein inhibitor (FAPI), which may have high sensitivity and specificity, has increased following the identification of FAP. We reviewed the current literature on [68Ga]-FAPI-based PET imaging techniques in the detection of female cancers and conducted a meta-analysis to determine the diagnostic performances of [68Ga]-FAPI-based PET imaging techniques for breast and gynecological cancers.
Improved gastrointestinal tolerance and iron status via probiotic use in iron deficiency anemia patients initiating oral iron replacement
Authors: şahintürk yasin , köker gökhan , köker gülhan özçelik , coşkuner ali , durmuş merve eren , çatlı mehmet mutlu , çekin ayhan hilmi
Published: September 2024

Background
Strategies that consider enhancing iron absorption and reducing gastrointestinal burden are important for effective iron replacement therapy (IRT) in patients with iron deficiency anemia (IDA)
Aim
To investigate gastrointestinal tolerability, treatment compliance and iron status markers in patients with IDA who received oral IRT with versus without concomitant Lactobacillus plantarum 299v (L. plantarum 299v) probiotic supplementation
Methods
A total of 295 patients with newly diagnosed IDA who were randomly assigned to receive either IRT alone (n = 157, IRT-only group) or IRT plus L. plantarum 299v (n = 138, IRT-Pro group) were included in this prospective randomized non-placebo, controlled study. Gastrointestinal intolerance symptoms, serum hemoglobin levels and iron status markers were recorded in each group.
Results
Overall, 91 (30.8%) of 295 patients reported gastrointestinal intolerance symptoms during IRT, and 30(10.2%) discontinued IRT within the first 30 days of treatment. Patients in the IRT-Pro group compared to those in the IRT-only group experienced significantly lower rates of gastrointestinal intolerance over the course of IRT (13.0% vs. 46.5%, p < 0.001) and treatment discontinuation within the first 30 days (3.6% vs. 15.9%, p < 0.001). At 3rd month of therapy, IRT-Pro vs. IRT-only group had significantly higher serum levels for iron (76.0(51.0–96.0) vs. 60.0(43.0–70.0) µg/dL, p < 0.001) and transferrin saturation (20.1(12.5–28.5) vs. 14.5(10.5–19.0) %, p < 0.001), in addition to higher change from baseline hemoglobin (0.9(0.3–1.3) vs. 0.4(-0.1-1.1) g/dL, p < 0.001) levels.
Conclusion
Use of L. plantarum 299v probiotic supplementation during the first 30 days of IRT in IDA patients significantly reduces the gastrointestinal burden of IRT (particularly abdominal pain and bloating), the likelihood of intolerance development (by ~ 3 times) and treatment discontinuation (by ~ 5 times), as accompanied with improved serum hemoglobin levels and serum iron markers.
Single Cell Droplet-Based Efficacy and Transcriptomic Analysis of a Novel Anti-KLRG1 Antibody for Elimination of Autoreactive T Cells
Authors: Konry Tania , Sulllivan Matthew , Rozzo Aldo , Ward Antonio , Rao Patricia , Soler-Ferran Dulce , Greenberg Steven
Published: September 2024

Progress in developing improvements in the treatment of autoimmune disease has been gradual, due to challenges presented by the nature of these conditions. Namely, the need to suppress a patient’s immune response while maintaining the essential activity of the immune system in controlling disease. Targeted treatments to eliminate the autoreactive immune cells driving disease symptoms present a promising new option for major improvements in treatment efficacy and side effect management. Monoclonal antibody therapies can be applied to target autoreactive immune cells if the cells possess unique surface marker expression patterns. Killer cell lectin like receptor G1 (KLRG1) expression on autoreactive T cells presents an optimal target for this type of cell depleting antibody therapy. In this study, we apply a variety of in vitro screening methods to determine the efficacy of a novel anti-KLRG1 antibody at mediating specific natural killer (NK) cell mediated antibody-dependent cellular cytotoxicity (ADCC). The methods include single-cell droplet microfluidic techniques, allowing timelapse imaging and sorting based on cellular interactions. Included in this study is the development of a novel method of sorting cells using a droplet-sorting platform and a fluorescent calcium dye to separate cells based on CD16 recognition of cell-bound antibody. We applied this novel sorting method to visualize transcriptomic variation between NK cells that are or are not activated by binding the anti-KLRG1 antibody using RNA sequencing. The data in this study reveals a reliable and target-specific cytotoxicity of the cell depleting anti-KLRG1 antibody, and supports our droplet-sorting calcium assay as a novel method of sorting cells based on receptor activation.
Evaluation of 5 Intermediate Microglia’s Structural Variations Within an Organotypic Hippocampal Slice Model After Regionalized Toxic Injury
Authors: Trejos Jesus , Schanne Francis
Published: September 2024

The dendritic cell of the CNS, the microglia (MG), is an initiation point of the immunological response within the post blood-brain barrier (BBB) compartment. Microglia drastically changes in response to cell stress to a much different non-dendritic morphology. This investigation postulates that if the first MG responses to toxic injury are isolated and studied in greater morphological detail there’s much to be learned about microglia’s metamorphosis from and M2 to an M1 state. The organotypic hippocampal slice was the experimental setting used to investigate microglial response to toxic injury; this isolates dendritic cell to post-BBB cells dynamics from the impact of nonspecific of in-vivo blood derived signaling. Within the context of biochemically verified precise toxic cell injury/death (induced with mercury or cyanide in combination with 2-deoxy-glucose) to a specific region within the hippocampal slice, MG’s morphological response was evaluated. There was up to 35% increase in microglia activation proximally to injury (CA3 region) and no changes distally (DG region) when compared to control slices treated with PBS. Maximum microglia activation consisted of a 3 plus-fold increase in the distance between the nucleus membrane and the cell membrane, which underscores an extensive and quantifiable amount of membrane rearrangement. This quantification can be applied to contemporaneous AI image analysis algorithms to demarcate and quantify relative MG activation in and around a site of injury. In between baseline and activated MG morphologies, 5 intermediate morphologies (or morphological behaviors) are described as it relates to its cell body, nucleus, and dendrites. The result from this study reconciles details of MG’s structure to its holistic characteristics in relation to parenchymal cell stress.
Antagonism of tomato endophytic fungi against grey mold disease
Authors: Pourmad Alireza , Ebrahimi Leila , Fotouhifar Khalil-Berdi
Published: September 2024

Endophytic fungi are a group of microorganisms living inside plant tissues without any immediate and visible symptoms, and in most cases have benefits for their host. In this research, 50 samples of healthy tomato plants were collected from Isfahan and Tehran provinces of Iran. Totally, 89 strains of endophytic fungi were isolated from root, stem, and leaf tissues. Based on morphological characteristics, the isolates were belonged to 12 different genera including Fusarium, Alternaria, Cladosporium, Acremonium, Arthrinium, Aspergillus, Penicillium, Moniliophthora, Rhizoctonia, Nigrospora, Trichoderma and Colletotrichum. The biocontrol effects of the isolates were investigated against Botrytis cinerea in vitro. Based on the results of dual culture and volatile organic compounds (VOC) production, six isolates were selected with the most inhibitory effect on B. cinerea that were belonging to the genus Fusarium. Among them, isolate 41R1 with 65.8 and 65% inhibitory rate on mycelia growth of the isolates B1 and B2, respectively, showed the highest value in the dual culture test. In the VOC test, isolate 28S1 had the most inhibitory effect on mycelia growth of isolates B1 and B2, with the values of 66.6 and 62.6%, respectively. Six selected isolates reduced the tomato grey mold disease severity about 35 to 58% in greenhouse. Isolate 28S1 increased the plant dry weight, but without significant effect on other plant growth indices. Isolates 41R1, 28S1, and 16S3 with the highest inhibition, were identified based on the partial sequence of tef-1α gene, which belonged to Fusarium falciforme, Fusarium falciforme and Fusarium solani species, respectively.
Molecular characteristics of human respiratory syncytial virus infection: an outbreak in children in 2023, Beijing, China
Authors: Huang Luci , Liu Ying , Li Fei , Fu Yiliang , Guan Xiaolei , Tian Xiaoyi , Zhang Xiaofei , Zhang Wei , Huo Jianbo , Song Wenqi , Xie Zhengde , Chen Xiangpeng
Published: September 2024

A resurgent outbreak of children respiratory syncytial virus (RSV) infection occurred on April 2023, Beijing. To elucidate the dominant genotypes and molecular characteristics of RSV isolates, totally 11 partial G gene sequences were obtained. Six RSVA and five RSVB isolates were clustered into ON1 and BA9 genotypes. Amino acid substitutions T113I, V131D, H258Q, and H266L were co-occurrences in four RSVA isolates. One strain had a substitution to S174N in T cell epitope of RSVA G protein. In RSVB G protein, P237L, P247T, K258N/S, H259Y, T266I, N296Y, T302I, and E305K were newly found but not in our previous study.
Integrative Genetics and Multiomics Analysis Unveil Mechanisms and Therapeutic Targets in Vitiligo: Insights from GWAS-meta, Microarray, Single-cell Transcriptomics, and ChIP-seq Data, Highlighting JAK/STAT Pathway Regulation of CTSS in Vitiligo
Authors: Dong Zi-yue , He Ming-jie , Yu Yong-kai , wang Kun , Wang Fang , Ran De-long , Fu De-shuang , He Qing , Yang Run-ping , Zhang Jiang-an
Published: September 2024

Background:
Vitiligo is a complex autoimmune disease characterized by the loss of melanocytes, leading to skin depigmentation. Despite advances in understanding its genetic and molecular basis, the precise mechanisms driving vitiligo remain elusive. Integrating multiple layers of omics data can provide a comprehensive view of disease pathogenesis and identify potential therapeutic targets.
Methods:
We first performed a genome-wide association study (GWAS) meta-analysis and druggability assessment using the latest data from FinnGen, the GWAS Catalog, and the UK Biobank. We subsequently investigated pathogenic and protective genes associated with vitiligo via summary-based Mendelian randomization (SMR) analysis across multiple eQTL and pQTL databases to construct a transcription factor regulatory network. Finally, we validated the genetically associated and causal genes identified in the previous analyses via microarray and single-cell RNA sequencing data.
Results:
The GWAS-meta analysis identified five genes with potential druggability: ERBB3, RHOH, CDK10, MC1R, and NDUFAF3. Drug target exploration and molecular docking were performed for these genes. SMR analysis revealed that five genes—CTSS, CTSH, STX8, KIR2DL3, and GRHPR—are causally associated with vitiligo at both the pQTL and eQTL levels. By integrating microarray and single-cell transcriptomic data, we detected differential expression of CTSS and its transcription factor STAT1/3 in both the blood and lesional skin of vitiligo patients.
Conclusions:
Our integrative multiomics approach provides new insights into the genetic and molecular mechanisms underlying vitiligo. The JAK/STAT pathway may contribute to vitiligo pathogenesis by regulating CTSS, which is involved in melanocyte antigen processing and presentation. Future research should focus on validating these findings and exploring the therapeutic potential of CTSS and genetically associated genes.
Irisin Prevents High-Fat Diet-Induced Metabolic Disorders via Brown Adipose Tissue Activation
Authors: Peng Xin-Gui , Dai Jingyue , Zhao Yufei , Chen Yue , Jiang Yang , Sun Rui , Tang Xingzhe , Cui Ying , Mao Hui
Published: September 2024

Background
High-fat diet (HFD) induces negative effects on interscapular brown adipose tissue (iBAT) activity and systemic energy metabolism. Irisin, a small hormonal agent known to modulate metabolism has been used for intervening HFD induced obesity. However, its mechanism of actions on iBAT function remains to be fully elucidated. This study sought to investigate whether an intervention with irisin could restore the thermogenic function of iBAT in HFD-induced mice with obesity, thereby regulating systemic metabolism.
Methods
Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) were used to determine and follow the changes of thermogenic capacity of iBAT and systemic metabolism in mice with obesity and iBAT-deficient mice during intervention with irisin for varying periods of time. Pathological and molecular biology analyses were performed on tissue and blood samples.
Results
Prolonged HFD feeding in mice induced obesity and impaired the thermogenic capacity of iBAT. MRI showed that irisin intervention decreased lipid content in iBAT, coupled with increased uncoupling protein 1 (UCP 1) expression and glucose analogue uptake capacity. This restoration of iBAT activity was accompanied by an improvement in systemic metabolism. The beneficial effects of irisin appears to be dependent on the length of intervention time. When iBAT was removed, the positive effects of irisin were partially suppressed, suggesting that irisin regulates metabolism through the restoration of the thermogenic function of iBAT.
Conclusions
HFD results in reduced thermogenic capacity of iBAT, while irisin intervention can effectively restore iBAT function, leading to improvement in overall glucose and lipid metabolism.
Is a picture worth the same emotions everywhere? Validation of images from the Nencki Affective Picture System in Malaysia
Authors: Berezina Elizaveta , Lee Ai-Suan , Gill Colin Mathew Hugues D. , Chua Jie Yun
Published: September 2024

Several validated image sets, such as NAPS, IAPS, GAPED, and OASIS, have been developed to elicit affective states. However, these image sets were primarily validated on Western populations within European and American contexts, and none have been fully validated in a Southeast Asian sample, where emotional restraint may also be valued similarly to the East Asian contexts. This study aimed to validate and provide norms for the Nencki Affective Picture System (NAPS; Marchewka et al., 2014) within a Malaysian sample. Subsets from the 1,356 NAPS images consisting of five image categories (faces, people, objects, landscapes, animals) were presented sequentially to 409 Malaysian adults aged 18 and above, who rated images for valence, arousal and approach/avoidance on a 9-point Likert scale. Valence, arousal and approach/avoidance norms were compared against the original European sample. Malaysian men and women rated images with lower valence and motivation than Europeans, but Malaysian men showed higher arousal ratings compared to European men, while Malaysian women exhibited the opposite pattern, with lower arousal ratings than European women. A linear regression was found instead of a classic ‘boomerang’ shaped quadratic regression previously observed in Western samples, suggesting that emotional suppression may be at play, in line with social norms. The Malaysian normative ratings will be freely available to all researchers.
Use of routinely collected health data (England) to identify subsequent disease-related events in patients with primary breast cancer: A practical alternative to hospital-based follow-up for breast cancer clinical trials
Authors: Kilburn Lucy Suzanne , Hinder Victoria , Ndebele-Mahati Sikhuphukile Gillian , Bliss Judith M
Published: September 2024

Background: With continued improvements in breast cancer (BC) outcomes and risk of recurrence occurring until at least 20 years post-diagnosis, it is important to continue to follow-up clinical trial participants to characterise long-term treatment impact. Traditionally follow-up has been via hospitals; entailing burden on patients and site-staff. Using routinely collected health datasets (RCHD) as an alternative method is attractive, but historically cancer recurrence is poorly recorded unlike initial cancer diagnosis. Here we use data collected prospectively from large, multi-centre BC clinical trials to develop and test a procedure to identify recurrence within RCHD.
Methods: Data from four trials of early breast cancer (TACT2, POETIC, IMPORT-HIGH and FAST-Forward) where recurrence data has been collected prospectively (gold standard) was linked with RCHD (incl. cancer registry and hospital episode statistics; HES) managed by NHS England. The procedure identified episodes of clinical activity within RCHD to classify each event type (local and distant recurrence, second cancers, death) separately then combined to derive time-to-recurrence (TTR), disease-free survival (iDFS) and overall survival (OS) outcomes. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Hazard ratios using Cox regression modelling, log rank test p-values and three-year survival-rates for the randomised treatments were reported separately for RCHD and trial data.
Results:
The final procedure used Cancer Registry diagnoses to identify initial BCs for quality control purposes and second primary cancers. Deaths were identified via death dates and cause. Distant recurrence was identified predominately by direct indicators of metastases (e.g. ICD10 codes C77X-79X). Local recurrence was identified via relevant surgeries’ OPCS4 codes. For TTR, iDFS and OS, agreement between study and RCHD events was reasonable. Specificity was good across all endpoints (range:97.9%-99.9% for three training datasets combined), as was NPV (range:95.2%-99.6%). Sensitivity and PPV were more variable with sensitivity ranging between 72.9%-97.2% and PPV ranging between 82.6%-99.5%. Values were similar when considering the test dataset. Survival estimates for TTR, iDFS and OS were similar between study and RCHD data.
Conclusion:It is possible, with reasonable accuracy, to identify cancer recurrences using RCHD in the place of hospital-based data collection after the point of primary analysis.
Herpes Zoster Presenting with Urinary Tract Irritation as the Initial Symptom in a COVID- 19 Patient
Authors: Cao Yuan , Zheng Yumin , Hu Xinhua , Li Jun
Published: September 2024

Background
Bladder symptoms, an atypical manifestation of herpes zoster (HZ), usually occur after a vesicular eruption and can present as urinary retention or loss of sensation, especially in immunocompromised patients. Here, we report a case of a patient who presented with urinary irritation preceding the skin lesion symptoms while concurrently experiencing COVID-19.
Case presentation
A 67-year-old male presented with repeated episodes of frequent micturition. Initial examinations, including blood tests, urinalysis, and ultrasound of the urinary system, ruled out urinary infection or organic disorder. The patient was subsequently diagnosed with COVID-19 and received in-home treatment. Despite resolution of COVID-19 symptoms, urinary irritation persisted. Unusual skin changes in the groin area were observed, leading to a diagnosis of herpes zoster. As herpes zoster improved, urinary symptoms gradually eased, and the patient returned to his pre-illness condition by discharge.
Conclusions
This case highlights an atypical presentation of herpes zoster with urinary tract irritation preceding the characteristic skin rash, potentially leading to initial diagnostic misjudgment. The patient's symptoms emerged following a COVID-19 infection, suggesting a possible link between SARS-CoV-2 and the reactivation of varicella-zoster virus. Early recognition and appropriate management of such atypical presentations are crucial, especially in post-COVID-19 patients.
The association between the extent of dissection observed by intravascular ultrasound and long-term progression of vessel lesions after drug-coated balloon angioplasty in patients with de novo coronary artery disease
Authors: Feng Lijun , Sun Yong , Li Changling , Dong Liang , Chen Han , Jiang Jun
Published: September 2024

Objective: This study aimed to investigate the correlation between the extent of dissection and long-term progression of vessel lesions (LPVL) after drug-coated balloon (DCB) angioplasty in patients with de novo coronary disease.
Methods: Patients who underwent DCB angioplasty and intravascular ultrasound (IVUS) assessment for de novo coronary lesions were retrospectively observed. The dissections were reclassified based on IVUS images, while the angiogram, post-DCB angioplasty and follow-up angiogram were analyzed using qualitative coronary angiography (QCA). The primary endpoint was the median 12-month follow-up angiographic result of target vessel stenosis.
Results：The present study involved 115 patients who were divided into two groups based on LPVL<5%: the progression group (n=51) and the non-progression group (n=64). The median follow-up period was 12 months (IQR 6-13 months). At baseline, the result of dissection type (p=0.003) and non-small vessel disease (NSVD) status (p=0.044) were significantly different between the two groups. Univariate logistic regression analysis of LPVL revealed that dissection type (odds ratio 1.70; 95% CI: 1.27-2.29; p<0.0001) and NSVD (odds ratio: 0.39; 95% CI: 0.17-0.91; p=0.029) were predictors of LPVL. However, according to multiple logistic regression, only dissection type (odds ratio: 1.73; 95% CI: 1.13-2.66; p=0.0124) was identified as an independent predictor of LVPL.
Conclusion： The severity of dissection type after DCB angioplasty was significantly associated with LPVL. Although there was a significant difference between small vessel disease and non-small vessel disease treated with a DCB, it was not an independent predictor of LPVL. It is recommended to assess de novo coronary lesions by IVUS after DCB angioplasty.
A prospective randomized study of the efficacy of continuous active warming in patients undergoing laparoscopic gastrectomy
Authors: Luo Mengjia , Feng Xiangying , Dai Yanran , Wang Yujie , Guo Xin , Du Juan , Ji Gang , Lang Hongjuan
Published: September 2024

Despite evidence has shown that the core temperature below 36℃ under surgery would lead to a sequence of adverse complications, and active warming measures are taken in order to reduce the incidence of the intraoperative hypothermia, core temperature disturbance during laparoscopic gastrectomy is common. The purpose of this research was to determine if a significant difference between continuous active warming (CAW) and active warming when body temperature is below 36℃ (BAW) in terms of incidence of intraoperative hypothermia and clinical rehabilitation in patients undergoing laparoscopic gastrectomy surgery. Patients assigned to CAW group were warmed immediately since the surgical incision procedure, the others were warmed while the body bladder temperature dropped to 36℃. The bladder temperature of the patient was recorded every 30 minutes during the operation. The primary outcome was the incidence of intraoperative hypothermia. Secondary outcomes included presence of shivering and agitation after operation, the time from end of surgery to tracheal extubation, postoperative pain score, the time to first postoperative flatus, postoperative complications, and the inflammatory markers. The overall incidence of hypothermia was 16.13% in 62 patients who underwent elective total laparoscopic radical gastrectomy. The incidence of shivering and agitation after operation was both 3.23% in CAW group, and it was 32.26% and 29.03% in BAW group. Time from end of surgery to tracheal extubation in CAW group was significantly lower than BAW group. In addition, continuous active warming could shorten time to first postoperative flatus of patients and relieve postoperative pain. In general, continuous active warming in patients undergoing laparoscopic gastrectomy decreased the incidence of intraoperative hypothermia and contributed to postoperative rehabilitation.
Clinical trial registration: Registered at Chinese Clinical Trial Registry (ChiCTR) on 20/07/2024.
Analysis of the macroseismic cumulative damage in the seismic sequences in Italy
Authors: Vannucci Gianfranco
Published: September 2024

During seismic sequences, macroseismic damage effects cannot always be distinguished and assigned with certainty to individual shocks. In particular, the intensity that quantifies the effects of the earthquakes is a measure of the cumulative effect of all the shocks that occurred. This affects the estimation of the macroseismic parameters that can be obtained (location, magnitude), which cannot have the same reliability as single mainshocks, with implications for seismotectonics or hazard assessment. To try to solve this problem, a methodology was recently proposed using the case study of the event of 2016, October 30th (Mw=6.6), based on the deletion of intensities above an established threshold for common localities hit by previous earthquakes during a sequence. In this paper, we analyse the variation of earthquake parameters of some Italian sequences by systematically applying this methodology and varying the cut threshold of intensity. The results provide a more complete evaluation of the proposed method and its reliability than classical processing based on all available MDPs.
Brain morphometric analysis in patients with glutaric aciduria type 1
Authors: Bian BingYang , Liu ChengXiang , Zhang Lei , Liu ZhuoHang , Tian Pu , Zhu XiaoNa , Liu Peng , Li Dan
Published: September 2024

This prospective study aimed to identify the affected brain structures and their functional correlations in the cortical and subcortical regions in patients with glutaric aciduria type 1 (GA-1). Seventeen patients with GA-1 and 17 healthy controls (HCs) were included (mean age, 38 ± 17 months; both contained 6 males). Three-dimensional-T1 weighted imaging data were acquired, voxel- and surface-based morphometry were used to quantitatively investigate differences in gray matter volume (GMV) and cortical thickness (CT) and to-sample t-tests were performed. Patients with GA-1 had lower GMV in the bilateral basal ganglia, thalamus, and limbic system, default mode network, and right cerebellum, and lower CT in the bilateral insula and lateral occipital cortex, right inferior parietal cortex, inferior temporal gyrus, and posterior cingulate cortex, than HCs. Patients with GA-1 had higher CT in the bilateral lingual gyrus, parahippocampal gyrus, superior frontal gyrus, left postcentral gyrus, right precuneus, precentral gyrus, middle temporal gyrus, and inferior temporal gyrus, than HCs. In GA-1 patients, blood glutaryl-carnitine levels correlated significantly with the GMV in the left inferior temporal gyrus. These brain morphological analyses revealed quantitative differences in the GMV and CT of GA-1 patients compared to HCs, and provided useful information about normal and abnormal neuroanatomy.
Study on degradation tracer and osteogenic ability of CS / NaYF4: Yb3+, Er3+ / AZ31 composites
Authors: Sun XiRao , Sun Danfang , Yin Xiumei , Li Dan , Liu Chang , Song Siyu , Wang Meng , Wang Chengyue
Published: September 2024

In order to reduce the degradation rate of magnesium alloys and improve their biocompatibility, polymers are often used to modify their surfaces. However, there is a lack of non-invasive means to detect degradation of polymer coatings, and tracking composite degradation is important for various of applications such as tissue engineering and drug delivery. Among various imaging tools, upconversion nanoparticles emitting visible light under near-infrared excitation hold promise in tracking post-implantation degradation of polymer composites. We therefore report a simple synthetic method to surface coat AZ31 magnesium alloy using chitosan and monitor its degradation by using the release of NaYF4: Yb3+, Er3+ encapsulated therein to cause a decrease in the fluorescence intensity of the coating. We found that the addition of the composite coating reduced the degradation rate of AZ31 magnesium alloy, improved its biocompatibility and verified its osteogenic ability, and that the fluorescence intensity of the composite coating had a linear relationship with the degradation time. Thus, in this study, the prepared AZ31-CN paved the way for non-invasive monitoring of the degradation behavior of the composite and could be the great candidate material for bone regeneration.