bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Evolution from Superradiant Instability to Stability in RN-f(R) Gravity Black Holes
Authors: CHEN WEN-XIANG , Zheng Yao-Guang
Published: July 2024

This paper investigates the potential evolution of RN-f(R) gravity black holes from superradiant instability to stability. By comparing the superradiant instability in black holes with the behavior of interface bound states in superconductors, we derive conditions under which superradiant instability can transition to stability. We employ the mathematical framework and formulas from the study of shot noise in superconducting tunnel junctions to illustrate the similarities and derive the conditions for the evolution of instability in black holes.
AS TECNOLOGIAS DE INFORMAÇÃO E COMUNICAÇÃO NA FORMAÇÃO DOCENTE EM GEOGRAFIA NO PARFOR
Authors: Lima Tiago Caminha , Mendes Tiago
Published: July 2024

O presente artigo possui como objetivo geral entender como as Tecnologias de Informação e Comunicação (TIC’s) estão presentes no processo de formação de professores no Programa Nacional de Formação de Professores da Educação Básica (Parfor), voltadas ao curso de Licenciatura em Geografia. A pesquisa é de cunho qualitativo e abordagem descritiva. Como resultado notou-se que a tecnologia mesmo sendo importante, como uma aliada no processo de ensino-aprendizagem, ainda não está firmada de forma sólida na Universidade Estadual do Piauí – UESPI, carecendo de inovações de forma a melhorar esse processo. Nesse sentido, a construção de um olhar crítico, por meio do uso das TIC’s, para o ensino geográfico contemporâneo, permitirá aos discentes e educadores construir uma geografia cada vez mais pautada em entender esse ciclo de interação entre o homem e o meio.
EDUCAÇÃO AMBIENTAL NO ENSINO DE GEOGRAFIA: VIVÊNCIAS NAS ESCOLAS RURAIS DO MUNICÍPIO DE FRUTAL (MG)
Authors: Souza Andreza Gomes
Published: July 2024

Almejamos apresentar neste artigo algumas considerações sobre a educação ambiental no ensino de Geografia, ressaltando o caso de três escolas rurais no município de Frutal (MG). Reafirmamos a relevância do saber geográfico para uma leitura de mundo despertadora da sensibilidade dos mais jovens, para a problemática ambiental. Para tanto foram realizadas entrevistas em três escolas rurais; dialogamos com os alunos, professoras, diretoras e moradores das comunidades. As problemáticas ambientais e sociais nem sempre estão presentes nos projetos desenvolvidos com as crianças e jovens. Isso evidencia a vigência de atividades fundamentadas na proposta política pedagógica pragmática que se distanciam do ideal crítico. Reconhecemos o avanço em relação à ocorrência de discussões, de trabalhos de campo e de questionamentos importantes realizados ao longo de ano letivo.
FEIRA LIVRE DO CRATO/CE: ENTRE PROTAGONISMO E DECADÊNCIA
Authors: Da Silva Tavares Cícero Antonio Jatanael
Published: July 2024

Este trabalho realiza uma abordagem sobre a feira livre do Crato/CE, no intuito de identificar os principais problemas enfrentados pelos feirantes que ocupam esse espaço. O ensejo da pesquisa surge em razão dessa feira livre ter sido considerada um importante fator econômico e cultural para o município, por atrair feirantes e consumidores de toda a região do Cariri cearense e estados adjacentes. Porém, é concebível entendê-la como um comércio em que se encontra em declínio, motivado por inúmeros fatores que serão descritos ao longo deste trabalho. Para alcançar os objetivos ora propostos, inicialmente fez-se o uso de levantamento bibliográfico, incluindo consultas a livros e artigos versando sobre outras feiras. Posteriormente, realizou-se um levantamento empírico, sendo aplicados questionários aos feirantes. Mediante a análise em estudo e de outras discutidas ao longo desta pesquisa, não restam dúvidas quanto ao fato dessa feira livre estar apresentando um processo decadente sob o viés econômico e cultural. Nesse sentido, surge a necessidade de uma reflexão a respeito.
APLICAÇÃO DA METODOLOGIA PEIR PARA A AVALIAÇÃO DE IMPACTOS AMBIENTAIS DO PERÍMETRO URBANIZADO DO RIACHO ANGOLA-CACHORRO EM LAGARTO/SE
Authors: Dantas Jonielton Oliveira , Fontes Andreia Reis
Published: July 2024

O presente estudo pretende analisar a viabilidade de aplicação da metodologia PEIR quanto à produção de indicadores de sustentabilidade que possibilitem a avaliação de impactos ambientais no perímetro urbanizado do riacho Angola-Cachorro no município de Lagarto/SE. Para tanto, foi aplicada a metodologia Pressão-Estado-Impacto-Resposta (P-E-I-R) adotada pelo Programa das Nações Unidas para o Meio Ambiente (PNUMA) para a promoção de cidades sustentáveis. Trata-se de um estudo de caso, de abordagem qualitativa, cuja impossibilidade de se obter dados mais específicos sobre as variáveis ambientais fez convergir para um estudo descritivo quanto ao objetivo. Contudo, o estudo apresentou indicadores de sustentabilidade que permitiram uma análise integrada dos aspectos socioambientais. Ademais, a metodologia PEIR se mostrou adequada ao objetivo pretendido, sendo um instrumento importante para a análise espacial, e de apropriação do geógrafo.
OS DESAFIOS DA COLETA SELETIVA NA MODALIDADE PONTO DE ENTREGA VOLUNTÁRIA – PEV NA ZONA LESTE DA CIDADE DE MANAUS
Authors: Santos Daniel Souza dos , Lima Vilma Terezinha de Araújo , Silva Gersica da Conceição
Published: July 2024

O crescimento populacional evidenciado nas últimas décadas em Manaus, aliado a um estilo de vida extremamente consumista, fez gerar, ao longo do tempo, vários problemas ambientais, relacionados especialmente ao descarte incorreto dos resíduos sólidos, que afetam de forma significativa o meio ambiente. Este trabalho teve como objetivo identificar os desafios da coleta seletiva na modalidade PEV, que estão inseridos em supermercados da Zona Leste (ZL) de Manaus. O método utilizado foi o quali-quantitativo e a pesquisa descritiva exploratória. Levando em consideração a população da ZL estimada em mais de 500 mil pessoas e o quantitativo de 4 (quatro) PEVs, significa que cada um deveria atender aproximadamente 125.000 (cento e vinte e cinco mil pessoas) da ZL, o que na prática não ocorre. Os PEVs recebem os resíduos sólidos que estão compreendidos nas categorias metal, plástico e papel, porém a pesquisa de campo identificou que nos contêineres existe apenas a referência para os plásticos, o que pode gerar dúvida ou desconhecimento do cliente que deseja depositar diversos tipos de materiais recicláveis nos PEVs. Na área de estudo, identificou-se três associações/cooperativas de catadores de materiais recicláveis, a ARPA, a COOPCAMARE e a Lixo e Cidadania, cadastradas na SEMULSP e que fazem parte da campanha de coleta seletiva da prefeitura de Manaus. Após passar por todas as etapas de tratamento, os materiais dos PEVs são organizados e encaminhados para comercialização nas empresas de beneficiamento.
Differences in checkpoint-inhibitor-induced hypophysitis: mono- versus combination therapy induced hypophysitis
Authors: van der Leij Stephanie , Suijkerbuijk Karijn P.M. , van den Broek Medard F.M. , Valk Gerlof D. , Dankbaar Jan Willem , van Santen Hanneke M.
Published: July 2024

Objective

Immune checkpoint inhibitors (ICIs) are revolutionary in oncology but may cause immune-related (IR) side effects, such as hypophysitis. Treatment with anti-PD-(L)1, anti-CTLA-4 or anti-CLTA-4/PD-1 may induce hypophysitis, but little is known about the differences in clinical presentation or need for different treatment. We analyzed the differences of anti-PD-(L)1, anti-CTLA-4 and anti-CTLA-4/PD-1 induced hypophysitis

Methods

retrospective analysis of 67 patients (27 anti-PD-(L)1, 6 anti-CLTA-4 and 34 anti-CTLA-4/PD-1 induced hypophysitis).

Results

The median time between starting ICIs and IR-hypophysitis was longer after anti-PD(L)-1) therapy (22 weeks versus 11 and 14 weeks after anti-CTLA-4 and anti-CTLA-4/PD-1 therapy, respectively). The majority of patients (>90%), presented with atypical complaints such as fatigue, nausea, and muscle complaints. Headache, TSH or LH/FSH deficiency were more common in anti-CTLA-4 and anti-CLTA-4/PD-1 versus anti-PD-(L)1 induced hypophysitis (83% and 58% versus 8%, 67% and 41% versus 11%, and 83% and 48% versus 7%, respectively). Pituitary abnormalities on MRI (hypophysitis or secondary empty sella syndrome) were only seen in patients receiving anti-CTLA-4 or anti-CTLA-4/PD-1 therapy. Recovery from TSH, LH/FSH and ACTH deficiency was described in 92%, 70% and 0% of patients after a mean period of 14 and 104 days, respectively, and did not differ between patients who did or did not receive high-dose steroids.

Conclusion

The clinical presentation of IR-hypophysitis varies depending on the type of ICIs. MRI abnormalities were only seen in anti-CTLA-4 or anti-CTLA-4/PD-1 induced hypophysitis. Endocrine recovery is seen for LH/FSH and TSH deficiency but not for ACTH deficiency, irrespective of the corticosteroid dose.
Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma
Authors: Tsujikawa Takahiro , Ohno Kazuchika , Morita Kei-ichi , Saburi Sumiyo , Mitsuda Junichi , Yoshimura Kanako , Kimura Alisa , Morimoto Hiroki , Ogi Hiroshi , Shibata Saya , Akashi Takumi , Kurata Morito , Imoto Issei , Shimizu Yasushi , Kano Satoshi , Watanabe Akihito , Yamazaki Tomoko , Asada Yukinori , Hayashi Ryuichi , Saito Yuki , Ozawa Hiroyuki , Tsukahara Kiyoaki , Oridate Nobuhiko , Sano Daisuke , Horii Arata , Ueki Yushi , Maruo Takashi , Mukoyama Nobuaki , Hanai Nobuhiro , Fukusumi Takahito , Iwai Hiroshi , Fujisawa Takuo , Fujii Takashi , Nibu Ken-ichi , Iwae Shigemichi , Ueda Tsutomu , Chikuie Nobuyuki , Yasumatsu Ryuji , Matsuo Mioko , Umeno Hirohito , Ono Takeharu , Masuda Muneyuki , Toh Satoshi , Itoh Kyoko , Hirano Shigeru , Asakage Takahiro
Published: July 2024

Background

In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC.

Methods

The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing.

Results

Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses.

Conclusion

Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.
Nerve-Glial antigen 2: unmasking the enigmatic cellular identity in the central nervous system
Authors: Bottero Marta , Pessina Giada , Bason Caterina , Vigo Tiziana , Uccelli Antonio , Ferrara Giovanni
Published: July 2024

Chondroitin sulfate proteoglycans (CSPGs) are fundamental components of the extracellular matrix in the central nervous system (CNS). Among these, the Nerve-Glial antigen 2 (NG2) stands out as a transmembrane CSPG exclusively expressed in a different population of cells collectively termed NG2-expressing cells. These enigmatic cells, found throughout the developing and adult CNS, have been indicated with various names, including NG2 progenitor cells, polydendrocytes, synantocytes, NG2 cells, and NG2-Glia, but are more commonly referred to as oligodendrocyte progenitor cells. Characterized by high proliferation rates and unique morphology, NG2-expressing cells stand apart from neurons, astrocytes, and oligodendrocytes. Intriguingly, some NG2-expressing cells form functional glutamatergic synapses with neurons, challenging the long-held belief that only neurons possess the intricate machinery required for neurotransmission. In the CNS, the complexity surrounding NG2-expressing cells extends to their classification. Additionally, NG2 expression has been documented in pericytes and immune cells, suggesting a role in regulating brain innate immunity and neuro-immune crosstalk in homeostasis. Ongoing debates revolve around their heterogeneity, potential as progenitors for various cell types, responses to neuroinflammation, and the role of NG2. Therefore, this review aims to shed light on the enigma of NG2-expressing cells by delving into their structure, functions, and signaling pathways. We will critically evaluate the literature on NG2 expression across the CNS, and address the contentious issues surrounding their classification and roles in neuroinflammation and neurodegeneration. By unraveling the intricacies of NG2-expressing cells, we hope to pave the way for a more comprehensive understanding of their contributions to CNS health and during neurological disorders.
Therapeutic strategies focusing on immune dysregulation and neuroinflammation in rosacea
Authors: Tu Kuan-Yi , Jung Chiau-Jing , Shih Yi-Hsien , Chang Anne Lynn S.
Published: July 2024

Rosacea is a complex inflammatory condition characterized by papulopustular lesions and erythema on the central face for which there is no cure. The development of rosacea is influenced by both external triggers and genetics, but the common pathophysiology is overactivation of the immune system. Here, we review the current data on proinflammatory cytokines and dysregulation of the neurovascular system as targetable components of rosacea. Amelioration of cutaneous and gastrointestinal dysbiosis and other external factors impacts the immune state and has been observed to improve rosacea. While multiple treatments exist, many patients do not achieve their goals for rosacea control and highlights an unmet need for dermatologic care. Current interventions encompass topical/oral drugs, light devices, and avoidance of triggers management. Additional understanding of the underlying pathogenesis may help us develop novel targeted therapeutic strategies to improve rosacea.
Organoids: new frontiers in tumor immune microenvironment research
Authors: Yang Yujia , Cui Jinlei , Kong Yajie , Hou Yu , Ma Cuiqing
Published: July 2024

The tumor microenvironment (TME) contains cells that regulate medication response and cancer growth in a major way. Tumor immunology research has been rejuvenated and cancer treatment has been changed by immunotherapy, a rapidly developing therapeutic approach. The growth patterns of tumor cells in vivo and the heterogeneity, complexity, and individuality of tumors produced from patients are not reflected in traditional two-dimensional tumor cell profiles. On the other hand, an in vitro three-dimensional (3D) model called the organoid model is gaining popularity. It can replicate the physiological and pathological properties of the original tissues in vivo. Tumor cells are the source of immune organoids. The TME characteristics can be preserved while preserving the variety of tumors by cultivating epithelial tumor cells with various stromal and immunological components. In addition to having genetic and physical similarities to human diseases and the ability to partially reconstruct the complex structure of tumors, these models are now widely used in research fields including cancer, developmental biology, regenerative mechanisms, drug development, disease modeling, and organ transplantation. This study reviews the function of organoids in immunotherapy and the tumor immune milieu. We also discuss current developments and suggest translational uses of tumor organoids in immuno-oncology research, immunotherapy modeling, and precision medicine.
Association between inflammatory bowel disease and osteoporosis in European and East Asian populations: exploring causality, mediation by nutritional status, and shared genetic architecture
Authors: Kang Jian , Wu Xize , Li Yue , Zhao Shuangli , Wang Shixuan , Yu Dongdong
Published: July 2024

Background

While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear.

Objective

Our study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations.

Methods

We performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway.

Results

Our analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants.

Conclusion

Our findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role.
Development and validation of a predictive model assessing the risk of sarcopenia in rheumatoid arthritis patients
Authors: Qu Yuan , Zhang Lili , Liu Yuan , Fu Yang , Wang Mengjie , Liu Chuanguo , Wang Xinyu , Wan Yakun , Xu Bing , Zhang Qian , Li Yancun , Jiang Ping
Published: July 2024

Background

Sarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients.

Methods

Patients with RA diagnosed between August 2022 and January 2024 were included and randomized into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and multifactorial logistic regression analysis were used to screen the risk variables for RA-associated muscle loss and to create an RA sarcopenia risk score. The predictive performance and clinical utility of the risk model were evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC), along with the calibration curve and clinical decision curve (DCA).

Results

A total of 480 patients with RA were included in the study (90% female, with the largest number in the 45–59 age group, about 50%). In this study, four variables (body mass index, disease duration, hemoglobin, and grip strength) were included to construct a nomogram for predicting RA sarcopenia. The training and validation set AUCs were 0.915 (95% CI: 0.8795–0.9498) and 0.907 (95% CI: 0.8552–0.9597), respectively, proving that the predictive model was well discriminated. The calibration curve showed that the predicted values of the model were basically in line with the actual values, demonstrating good calibration. The DCA indicated that almost the entire range of patients with RA can benefit from this novel prediction model, suggesting good clinical utility.

Conclusion

This study developed and validated a nomogram prediction model to predict the risk of sarcopenia in RA patients. The model can assist clinicians in enhancing their ability to screen for RA sarcopenia, assess patient prognosis, make early decisions, and improve the quality of life for RA patients.
A high-precision positioning method for deep-towed multichannel seismic arrays
Authors: Wei Zhengrong , Pei Yanliang , Zhu Xiangqian , Liu Kai , Zhang Xiaobo , Zong Le , Li Xinyu
Published: July 2024

Kuiyang-ST2000 is a deep-towed multichannel seismic system that provides high-resolution exploration of sub-seabed geological formations. Due to the uncertainty of the sound speed at full ocean depth, the travel-time positioning of sea surface reflected waves still has flaws in positioning arrays. This research reveals that the average sound speed of seawater selected for computing the array position only affects the vertical displacement of the arrays. thus, a polynomial fitting method is proposed to position the arrays. Because the nonuniform mass distribution complicates the array shape, first, the weight of the digital transmission unit is balanced by one designed floater so that the array shape becomes a simple convex curve during towing conditions. Afterward, one general sound speed is used to calculate the initial array position; then, the polynomial fitting method is used to tune the sound speed so that the seismic source and hydrophones are on the same convex curve. Finally, an accurate array position is calculated by the proposed positioning method, and the submarine shallow strata are imaged at a high resolution.
Mercury distribution and transfer in mangrove forests in urban areas under simulated rising sea levels
Authors: You Xilin , Sun Lumin , Chen Xiaozheng , Li Yiting , Zheng Jue , Yuan Dongxing , Wu Junjie , Sun Shiyu
Published: July 2024

This study assesses the impact of simulated sea level rise (SLR) on mercury distribution and migration in an urban mangrove wetland on the northern coast of Maluan Bay, Xiamen City, Fujian Province, China. Two adjacent Kandelia obovata mangrove plots with elevations representing current sea level and a 40-cm SLR were examined. Total mercury (THg), methylmercury (MeHg), and mercury isotopes in sediments from different elevations were analyzed to reveal the geochemical behavior of mercury under a simulated 100-year SLR scenario. THg and MeHg distribution in sediments mirrored patterns of biogenic elements (carbon, nitrogen, and phosphorus), suggesting adsorption onto organic matter as the primary entry mechanism. Low-elevation plots showed significantly higher concentrations of THg, MeHg, total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP) compared to high-elevation plots. Mercury isotope characteristics indicated that the primary mercury source was anthropogenic emissions from surrounding lands, entering the wetland from both landward and seaward directions. The study highlights the crucial role of mangrove wetlands in mercury pollution control and nutrient cycling under SLR conditions. Results suggest that SLR enhances the retention capacity of mangrove wetlands for THg, MeHg, and nutrients. This research provides a scientific basis for mangrove conservation and restoration, offering new insights into the geochemical behavior of mercury in vegetated intertidal ecosystems in the context of climate change.
Synthesis and performance evaluation of low-molecular-weight biobased polyester rubber as a novel eco-friendly polymeric plasticizer for polyvinyl chloride
Authors: Zhang Qinan , Sun Jiahui , Yao Zehao , Ding Xuejia , Wang Zhao , Zhang Liqun
Published: July 2024

Developing eco-friendly polymeric plasticizers with excellent migration resistance is one of the research hotspots in the polyvinyl chloride (PVC) industry. A low-molecular-weight biobased polyester rubber (LMW-BPR) was synthesized from five biobased polyester monomers in a 100-L reactor and evaluated as a potential eco-friendly polymeric plasticizer for PVC. The obtained LMW-BPR is an amorphous polyester material with a low glass transition temperature of −48°C and a molecular weight of 22 kg/mol, which is lower than that of existing polyester rubber but higher than those of most polyester plasticizer commodities. Plasticized PVC composites with a total plasticizer content of 50 phr were prepared by using the mixture of LMW-BPR and di-isononyl cyclohexane-1,2-dicarboxylate (DINCH, an eco-friendly monomeric plasticizer commodity) as the plasticizer. The migration resistance test showed that the migration loss of plasticizer in plasticized PVC composite decreased significantly with the increase of LMW-BPR content. When the content of LMW-BPR reaches 30 phr, the plasticized PVC composites are almost nonmigratory. In addition, compared with PVC composite plasticized by pure DINCH, co-plasticized PVC composites containing LMW-BPR exhibit higher tensile strength and thermal stability, and their flexibility, low-temperature resistance and biocompatibility are also maintained at a similar level to the former. Overall, LMW-BPR is an effective eco-friendly polymeric plasticizer for PVC and also sustainable and scalable, thus it is worthy of wide application.
A dose–response correlation between smoking and severity of acute pancreatitis: a propensity score-matched study
Authors: Li Runzhuo , Tang Wanyun , Yan Sun , Yu Xiaohan , Hu Lian
Published: July 2024

Background

Acute pancreatitis, among the most prevalent gastrointestinal disorders, exhibits a continual rise in its incidence recent years. This study endeavor to explore the correlation between smoking exposure and the severity of acute pancreatitis (AP).

Methods

Five hundred and eight patients diagnosed as acute pancreatitis (AP) were included in our data analysis. Patients were categorized based on their smoking pack-years into four groups: light, moderate, heavy, and non-smokers. Outcomes were classified as two: “mild acute pancreatitis (MAP)” and “moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP)”. We conducted propensity score matching (PSM) to adjust confounding factors and multivariable logistic regression analysis to determine adjusted odds ratios and 95% confidence intervals. Additionally, a dose-dependent association analysis between smoking exposure and the incidence rate of “MSAP or SAP” was performed.

Results

Smokers exhibited a higher risk of “MSAP or SAP” compared to non-smokers, both before (17.1 vs. 54.9%, p < 0.001) and after (9.4 vs. 24.7%, p < 0.001) PSM. With an area under the ROC curve of 0.708, smoking showed a moderate level of predictive ability. Furthermore, propensity score matching analysis showed that patients who smoked compared to non-smokers had significantly higher risks of “MSAP or SAP” for light smoking (OR 3.76, 95% CI 1.40–10.07, p = 0.008), moderate smoking (OR 4.94, 95% CI 2.23–10.92, p < 0.001), and heavy smoking (OR 8.08, 95% CI 3.39–19.25, p < 0.001).

Conclusion

Smoking is an independent risk factor that can raise the severity of pancreatitis. Moreover, the severity of acute pancreatitis escalates in tandem with the accumulation of pack-years of smoking.
Drug repurposing in Rett and Rett-like syndromes: a promising yet underrated opportunity?
Authors: Fuchs Claudia , ‘t Hoen Peter A. C. , Müller Annelieke R. , Ehrhart Friederike , Van Karnebeek Clara D. M.
Published: July 2024

Rett syndrome (RTT) and Rett-like syndromes [i.e., CDKL5 deficiency disorder (CDD) and FOXG1-syndrome] represent rare yet profoundly impactful neurodevelopmental disorders (NDDs). The severity and complexity of symptoms associated with these disorders, including cognitive impairment, motor dysfunction, seizures and other neurological features significantly affect the quality of life of patients and families. Despite ongoing research efforts to identify potential therapeutic targets and develop novel treatments, current therapeutic options remain limited. Here the potential of drug repurposing (DR) as a promising avenue for addressing the unmet medical needs of individuals with RTT and related disorders is explored. Leveraging existing drugs for new therapeutic purposes, DR presents an attractive strategy, particularly suited for neurological disorders given the complexities of the central nervous system (CNS) and the challenges in blood-brain barrier penetration. The current landscape of DR efforts in these syndromes is thoroughly examined, with partiuclar focus on shared molecular pathways and potential common drug targets across these conditions.
Restriction of growth and biofilm formation of ESKAPE pathogens by caprine gut-derived probiotic bacteria
Authors: Saini Prerna , Ayyanna Repally , Kumar Rishi , Bhowmick Sayan Kumar , Bhaskar Vinay , Dey Bappaditya
Published: July 2024

The accelerated rise in antimicrobial resistance (AMR) poses a significant global health risk, necessitating the exploration of alternative strategies to combat pathogenic infections. Biofilm-related infections that are unresponsive to standard antibiotics often require the use of higher-order antimicrobials with toxic side effects and the potential to disrupt the microbiome. Probiotic therapy, with its diverse benefits and inherent safety, is emerging as a promising approach to prevent and treat various infections, and as an alternative to antibiotic therapy. In this study, we isolated novel probiotic bacteria from the gut of domestic goats (Capra hircus) and evaluated their antimicrobial and anti-biofilm activities against the ‘ESKAPE’ group of pathogens. We performed comprehensive microbiological, biochemical, and molecular characterizations, including analysis of the 16S-rRNA gene V1-V3 region and the 16S-23S ISR region, on 20 caprine gut-derived lactic acid bacteria (LAB). Among these, six selected Lactobacillus isolates demonstrated substantial biofilm formation under anaerobic conditions and exhibited robust cell surface hydrophobicity and autoaggregation, and epithelial cell adhesion properties highlighting their superior enteric colonization capability. Notably, these Lactobacillus isolates exhibited broad-spectrum growth inhibitory and anti-biofilm properties against ‘ESKAPE’ pathogens. Additionally, the Lactobacillus isolates were susceptible to antibiotics listed by the European Food Safety Authority (EFSA) within the prescribed Minimum Inhibitory Concentration limits, suggesting their safety as feed additives. The remarkable probiotic characteristics exhibited by the caprine gut-derived Lactobacillus isolates in this study strongly endorse their potential as compelling alternatives to antibiotics and direct-fed microbial (DFM) feed supplements in the livestock industry, addressing the escalating need for antibiotic-free animal products.
Exosomes: a significant medium for regulating drug resistance through cargo delivery
Authors: Ren Bixuan , Li Xiaoqing , Zhang Zhihua , Tai Sheng , Yu Shan
Published: July 2024

Exosomes are small lipid nanovesicles with a diameter of 30–150 nm. They are present in all body fluids and are actively secreted by the majority of cells through the process of exocytosis. Exosomes play an essential role in intercellular communication and act as significant molecular carriers in regulating various physiological and pathological processes, such as the emergence of drug resistance in tumors. Tumor-associated exosomes transfer drug resistance to other tumor cells by releasing substances such as multidrug resistance proteins and miRNAs through exosomes. These substances change the cell phenotype, making it resistant to drugs. Tumor-associated exosomes also play a role in impacting drug resistance in other cells, like immune cells and stromal cells. Exosomes alter the behavior and function of these cells to help tumor cells evade immune surveillance and form a tumor niche. In addition, exosomes also export substances such as tumoricidal drugs and neutralizing antibody drugs to help tumor cells resist drug therapy. In this review, we summarize the mechanisms of exosomes in promoting drug resistance by delivering cargo in the context of the tumor microenvironment (TME).
A case report of dipeptidyl peptidase 4 inhibitor-related kidney disease combined with renal cancer
Authors: Kurihara Shigekazu , Sawa Naoki , Sumida Keiichi , Ikuma Daisuke , Oba Yuki , Mizuno Hiroki , Sekine Akinari , Yamanouchi Masayuki , Hasegawa Eiko , Suwabe Tatsuya , Urakami Shinji , Kono Kei , Kinowaki Keiichi , Ohashi Kenichi , Yamaguchi Yutaka , Ubara Yoshifumi
Published: July 2024

A kidney biopsy was performed in a 64-year-old woman with type 2 diabetes mellitus and less than 1 g of proteinuria who rapidly progressed to end-stage renal failure after approximately 2 years of treatment with two dipeptidyl peptidase 4 (DPP-4) inhibitors for type 2 diabetes mellitus. The biopsy revealed not only a coincidental diagnosis of renal cell carcinoma, which was not evident on pre-biopsy computed tomography, but also severe thrombotic microangiopathy (TMA)-like glomerular endothelial cell damage in the noncancerous areas. These results suggest that DPP4 inhibitors may have been involved in two kidney diseases.
A simple nomogram for predicting the mortality of PICU patients with sepsis-associated encephalopathy: a multicenter retrospective study
Authors: Wang Guan , Gao Yan , Fu Yanan , Huo Qin , Guo Enyu , Jiang Qin , Liu Jing , Jiang Xinzhu , Liu Xinjie
Published: July 2024

Background

As one of the serious complications of sepsis in children, sepsis-associated encephalopathy (SAE) is associated with significantly poor prognosis and increased mortality. However, predictors of outcomes for pediatric SAE patients have yet to be identified. The aim of this study was to develop nomograms to predict the 14-day and 90-day mortality of children with SAE, providing early warning to take effective measures to improve prognosis and reduce mortality.

Methods

In this multicenter, retrospective study, we screened 291 patients with SAE admitted to the PICU between January 2017 and September 2022 in Shandong Province. A least absolute shrinkage and selector operation (LASSO) method was used to identify the optimal prognostic factors predicting the outcomes in pediatric patients with SAE. Then, multivariable logistic regression analysis was performed based on these variables, and two nomograms were built for visualization. We used the area under the curve (AUC), calibration curves and decision curves to test the accuracy and discrimination of the nomograms in predicting outcomes.

Results

There were 129 patients with SAE in the training cohort, and there were 103 and 59 patients in the two independent validation cohorts, respectively. Vasopressor use, procalcitonin (PCT), lactate and pediatric critical illness score (PCIS) were independent predictive factors for 14-day mortality, and vasopressor use, PCT, lactate, PCIS and albumin were independent predictive factors for 90-day mortality. Based on the variables, we generated two nomograms for the early identification of 14-day mortality (AUC 0.853, 95% CI 0.787–0.919, sensitivity 72.4%, specificity 84.5%) and 90-day mortality (AUC 0.857, 95% CI 0.792–0.923, sensitivity 72.3%, specificity 90.6%), respectively. The calibration plots for nomograms showed excellent agreement of mortality probabilities between the observed and predicted values in both training and validation cohorts. Decision curve analyses (DCA) indicated that nomograms conferred high clinical net benefit.

Conclusion

The nomograms in this study revealed optimal prognostic factors for the mortality of pediatric patients with SAE, and individualized quantitative risk evaluation by the models would be practical for treatment management.
Causal association of dietary factors with five common cancers: univariate and multivariate Mendelian randomization studies
Authors: Yang Lin , Wang Li , Bao Erhao , Wang Jiahao , Zhu Pingyu
Published: July 2024

Background

Daily dietary habits are closely related to human health, and long-term unhealthy dietary intake, such as excessive consumption of alcohol and pickled foods, may promote the development of cancers. However, comprehensive research on the causal relationship between dietary habits and cancer is lacking. Therefore, this study aimed to reveal the potential causal link between dietary risk factors and the prognosis of cancer-related to genetic susceptibility.

Methods

GWAS (Genome-Wide Association Studies) summary data on dietary habits and five common types of cancer and their pathological subtypes were obtained from the UK Biobank and various cancer association consortia. A univariable two-sample Mendelian randomization (UVMR) and FDR correction analysis was conducted to explore the causal relationships between 45 dietary habits and five common types of cancer and their histopathological subtypes. In addition, multivariable Mendelian randomization analysis (MVMR) was performed to adjust for traditional risk factors for dietary habits, and the direct or indirect effects of diet on cancer were evaluated. Finally, the prognostic impact of selected instrumental variables on cancer was analyzed using an online data platform.

Results

In the UVMR analysis, four dietary habits were identified as risk factors for cancer, while five dietary habits were identified as protective factors. Among the latter, one dietary habit showed a significant association with cancer even after FDR correction, indicating a potential causal relationship. The MVMR analysis revealed that weekly beer and cider intake, may act as an independent risk factor for cancer development. Other causal associations between dietary habits and cancer risk may be mediated by intermediate factors. In the prognostic analysis, the SNPs (Single Nucleotide Polymorphisms) of average weekly beer and cider intake were set as independent risk factors and were found to significantly impact overall survival (OS) and cancer-specific survival (CSS) in lung cancer.

Conclusion

This causal relationship study supports the notion that adjusting daily dietary habits and specific dietary interventions may decrease the risk of cancer.
Poly (ADP-ribose) polymerase inhibitor therapy and mechanisms of resistance in epithelial ovarian cancer
Authors: Kulkarni Sanat , Gajjar Ketankumar , Madhusudan Srinivasan
Published: July 2024

Advanced epithelial ovarian cancer is the commonest cause of gynaecological cancer deaths. First-line treatment for advanced disease includes a combination of platinum-taxane chemotherapy (post-operatively or peri-operatively) and maximal debulking surgery whenever feasible. Initial response rate to chemotherapy is high (up to 80%) but most patients will develop recurrence (approximately 70-90%) and succumb to the disease. Recently, poly-ADP-ribose polymerase (PARP) inhibition (by drugs such as Olaparib, Niraparib or Rucaparib) directed synthetic lethality approach in BRCA germline mutant or platinum sensitive disease has generated real hope for patients. PARP inhibitor (PARPi) maintenance therapy can prolong survival but therapeutic response is not sustained due to intrinsic or acquired secondary resistance to PARPi therapy. Reversion of BRCA1/2 mutation can lead to clinical PARPi resistance in BRCA-germline mutated ovarian cancer. However, in the more common platinum sensitive sporadic HGSOC, the clinical mechanisms of development of PARPi resistance remains to be defined. Here we provide a comprehensive review of the current status of PARPi and the mechanisms of resistance to therapy.
CM082 suppresses hypoxia-induced retinal neovascularization in larval zebrafish
Authors: Zhang Jun-long , Fan Ding-gang , Yin Wu , Hu Bing
Published: July 2024

Retinal neovascularization is a common feature of several ocular neovascular diseases, which are the leading cause of blindness in the world. Current treatments are administered through invasive intravitreal injections, leading to poor patient compliance, serious ocular complications and heavy economic burdens. Thus, an alternative less or non-invasive therapeutic strategy is in demand. Here, a non-invasive oral tyrosine kinase inhibitor, CM082, was evaluated in a retinal neovascularization model induced by hypoxia in zebrafish larvae. We found that CM082 effectively suppressed retinal neovascularization, rescued cell loss in the retinal ganglion cell layer, and rescued the visual function deficiency. Our results elucidated that CM082 mediated its therapeutic efficacy primarily through the inhibition of Vegfr2 phosphorylation. The findings demonstrated that CM082 possessed strong antiangiogenic effects and may serve as a potential treatment for angiogenesis in ocular neovascular diseases.
Effect of lateral septum vasopressin administration on reward system neurochemistry and amphetamine-induced addictive-like behaviors in female rats
Authors: Gárate-Pérez Macarena Francisca , Cáceres-Vergara Daniela , Tobar Francisca , Bahamondes Carolina , Bahamonde Tamara , Sanhueza Claudia , Guzmán Fanny , Sotomayor-Zárate Ramón , Renard Georgina M.
Published: July 2024

Introduction: The chronic use of psychostimulants increases the risk of addiction and, there is no specific pharmacologic treatment for psychostimulant addiction. The vasopressin (AVP) system is a possible pharmacological target in drug addiction. Previous results obtained in our laboratory showed that amphetamine (AMPH) treatment decreases lateral septum (LS) AVP levels in male rats, and AVP microinjection in LS decreases addictive-like behavior. The aim of the present work was to investigate the effect of AMPH treatment on LS AVP levels and the effect of LS AVP administration on the expression of AMPH-conditioned place preference (CPP) in female rats. The secondary objectives were to study the effect of LS AVP administration on LS GABA and glutamate release in male and female rats and on nucleus accumbens (NAc) dopamine (DA) release in female rats.

Methods: Female rats were conditioned with AMPH (1.5 mg/kg i.p.) or saline for 4 days.

Results: Conditioning with AMPH did not change LS AVP content in females. However, AVP microinjection into the LS decreased the expression of conditioned place preference (CPP) to AMPH. Glutamate and GABA extracellular levels in the LS induced by AVP were studied in males and females. NAc GABA and DA extracellular levels induced by LS AVP microinjection in female rats were measured by microdialysis. In males, AVP perfusion produced a significant increase in LS GABA extracellular levels; however, a decrease in GABA extracellular levels was observed in females. Both in males and females, LS AVP perfusion did not produce changes in LS glutamate extracellular levels. Microinjection of AVP into the LS did not change GABA or DA extracellular levels in the NAc of females.

Discussion: Therefore, AVP administration into the LS produces different LS-NAc neurochemical responses in females than males but decreases CPP to AMPH in both sexes. The behavioral response in males is due to a decrease in NAc DA levels, but in females, it could be due to a preventive increase in NAc DA levels. It is reasonable to postulate that, in females, the decrease in conditioning produced by AVP microinjection is influenced by other factors inherent to sex, and an effect on anxiety cannot be discarded.
Neural regulation of mesenchymal stem cells in craniofacial bone: development, homeostasis and repair
Authors: Pi Huai-Jin , Huang Bo , Yuan Quan , Jing Jun-Jun
Published: July 2024

Mesenchymal stem cells endow various functions, including proliferation, multipotency, migration, etc. Craniofacial bones originate from the cranial neural crest and are developed mainly through intramembranous ossification, which are different from long bones. There are varied mesenchymal stem cells existing in the craniofacial bone, including Gli1 + cells, Axin2 + cells, Prx1 + cells, etc. Nerves distributed in craniofacial area are also derived from the neural crest, and the trigeminal nerve is the major sensory nerve in craniofacial area. The nerves and the skeleton are tightly linked spatially, and the skeleton is broadly innervated by sensory and sympathetic nerves, which also participate in bone development, homeostasis and healing process. In this review, we summarize mesenchymal stem cells located in craniofacial bone or, to be more specific, in jaws, temporomandibular joint and cranial sutures. Then we discuss the research advance concerning neural regulation of mesenchymal stem cells in craniofacial bone, mainly focused on development, homeostasis and repair. Discovery of neural regulation of mesenchymal stem cells may assist in treatment in the craniofacial bone diseases or injuries.
Comprehensive analysis of B3 family genes in pearl millet (Pennisetum glaucum) and the negative regulator role of PgRAV-04 in drought tolerance
Authors: Wang Yin-Hua , Ye Xing , Zhao Bi-Yao , Wang Wen-Jing , Zhou Zheng-Feng , Zhang Xiang-Qian , Du Juan , Song Jian-Ling , Huang Xiao-Ling , Ouyang Kun-Xi , Zhong Tian-Xiu , Liao Fei-Xiong
Published: July 2024

Introduction

Members of the plant-specific B3 transcription factor superfamily play crucial roles in various plant growth and developmental processes. Despite numerous valuable studies on B3 genes in other species, little is known about the B3 superfamily in pearl millet.

Methods and results

Here, through comparative genomic analysis, we identified 70 B3 proteins in pearl millet and categorized them into four subfamilies based on phylogenetic affiliations: ARF, RAV, LAV, and REM. We also mapped the chromosomal locations of these proteins and analyzed their gene structures, conserved motifs, and gene duplication events, providing new insights into their potential functional interactions. Using transcriptomic sequencing and real-time quantitative PCR, we determined that most PgB3 genes exhibit upregulated expression under drought and high-temperature stresses, indicating their involvement in stress response regulation. To delve deeper into the abiotic stress roles of the B3 family, we focused on a specific gene within the RAV subfamily, PgRAV-04, cloning it and overexpressing it in tobacco. PgRAV-04 overexpression led to increased drought sensitivity in the transgenic plants due to decreased proline levels and peroxidase activity.

Discussion

This study not only adds to the existing body of knowledge on the B3 family’s characteristics but also advances our functional understanding of the PgB3 genes in pearl millet, reinforcing the significance of these factors in stress adaptation mechanisms.