bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationship between beta-2 microglobulin and B-cell malignancies: genome-wide meta-analysis and a bidirectional two-sample Mendelian randomization study
Authors: Li Jiuling , Wu Yao , Zhang Xin , Wang Xueju 
Published: October 2024

BackgroundBeta-2 microglobulin (β2M) is acknowledged as a prognostic biomarker for B-cell malignancies. However, insights into the impact of β2M on B-cell malignancy risk, and vice versa, are limited.MethodsWe conducted a genome-wide meta-analysis (GWMA), bidirectional two-sample Mendelian randomization (TSMR) analysis, and pathway enrichment analysis to explore the causal relationship between β2M and B-cell malignancies and the underlying biological processes.ResultsThe GWMA identified 55 lead SNPs across five genomic regions (three novel: WDR72, UMOD, and NLRC5) associated with β2M. In the UKB, genetically predicted β2M showed a positive association with diffuse large B-cell lymphoma (DLBCL; odds ratio [OR]: 1.742 per standard deviation increase in β2M; 95% confidence interval [CI]: 1.215–2.498; P = 3.00 × 10−3; FDR = 7.50× 10−3) and Hodgkin lymphoma (HL; OR: 2.270; 95% CI: 1.525–3.380; P = 5.15 × 10−5; FDR =2.58 × 10−4). However, no associations were found with follicular lymphoma (FL), chronic lymphoid leukemia (CLL), or multiple myeloma (MM). Reverse TSMR analysis revealed no association between genetically predicted B-cell malignancies and β2M. In FinnGen, β2M was found to be associated with an increased risk of DLBCL (OR: 2.098; 95% CI: 1.358-3.242; P = 8.28 × 10−4; FDR = 4.14 × 10−3), HL (OR: 1.581; 95% CI: 1.167-2.142; P = 3.13 × 10−3; FDR = 5.22 × 10−3), and FL (OR: 2.113; 95% CI: 1.292-3.455; P = 2.90 × 10−3; FDR = 5.22 × 10−3). However, no association was found with CLL or MM. Reverse TSMR analysis indicated that genetically predicted DLBCL, FL, and MM may perturb β2M levels. Pathway enrichment analysis suggested that the innate immune system represents a convergent biological process underlying β2M, DLBCL, and HL.ConclusionsOur findings suggested that elevated levels of β2M were associated with an increased risk of DLBCL and HL, which is potentially linked to dysfunction of the innate immune system.
Body compositions phenotypes of older adults with COPD
Authors: Kaluźniak-Szymanowska Aleksandra , Talarska Dorota , Tobis Sławomir , Styszyński Arkadiusz , Cofta Szczepan , Wieczorowska-Tobis Katarzyna , Deskur-Śmielecka Ewa 
Published: October 2024

PurposeChanges in nutritional status are important extrapulmonary manifestations of the chronic obstructive pulmonary disease (COPD). The study aimed to assess the prevalence of different body composition phenotypes in older patients with COPD and to investigate the relationship between these phenotypes and the severity of the disease, as well as physical performance of the subjects.Patients and methodsThe study included 124 subjects aged ≥60 with COPD. In all of them body composition analysis and muscle strength measurement were performed. Additionally, data from patients’ medical records were analyzed. Study sample was divided into four groups based on the phenotypic body composition: normal phenotype (N), sarcopenia, obesity and sarcopenic obesity (SO).ResultsIncidence of sarcopenia was significantly higher in patients with severe or very severe COPD based on GOLD in comparison with subjects with mild or moderate obstruction (p = 0.043). Participants with sarcopenia, obesity and SO had lower results of the 6-min walk test than subjects with N (225.77 m, 275.33 m, 350.67 m, 403.56 m, respectively). Moreover, sarcopenia and SO had lower results than obesity (p = 0.001, p = 0.041, respectively).ConclusionSarcopenia is common in patients with advanced COPD. Sarcopenia and SO are associated with poorer physical performance. All older people with COPD should routinely have their body composition assessed, instead of simply measuring of body weight or body mass index (BMI).
Comparative analysis of COVID-19 responses in Japan and Africa: diet, phytochemicals, vitamin D, and gut microbiota in reducing mortality—A systematic review and meta-analysis
Authors: Santa Kazuki , Tamaki Raita , Watanabe Kenji , Nagaoka Isao 
Published: October 2024

BackgroundAs the novel coronavirus disease 2019 (COVID-19) pandemic subsides, the clinical sequelae are becoming more problematic. Interestingly, the statistical data indicate that Africa has experienced the lowest number of cases and deaths, with an unexpected phenomenon where the number of deaths from COVID-19 has not increased significantly. Several studies have investigated the relationship between diet and coronavirus. However, no systematic review/meta-analysis has conclusively linked diet (phytochemicals and vitamin D) and the gut microbiota in the context of COVID-19.MethodsThis study examined the responses to COVID-19 in Japan and Africa, formulating the following hypotheses: (1) a healthy diet is effective against COVID-19, (2) blood vitamin D levels are associated with COVID-19 mortality, and (3) COVID-19 is associated with the gut microbiota. To investigate these hypotheses, a keyword search and meta-analysis were conducted using PubMed, and each hypothesis was tested.ResultsThis study found that a healthy diet, particularly rich in phytochemicals such as polyphenols and flavonoids, is effective against COVID-19. An association was detected between blood vitamin D levels and COVID-19 mortality. The gut microbiota was linked to COVID-19 and its amelioration. These findings may have significant implications for not only understanding COVID-19 but also future prevention of pneumonia.
RUNX2 as a novel biomarker for early identification of patients progressing to advanced-stage mycosis fungoides
Authors: Danielsen Maria , Emmanuel Thomas , Nielsen Morten Muhlig , Lindahl Lise Maria , Gluud Maria , Ødum Niels , Raaby Line , Steiniche Torben , Iversen Lars , Bech Rikke , Buus Terkild Brink , Johansen Claus 
Published: October 2024

IntroductionThe majority of patients with mycosis fungoides (MF) have an indolent disease course, but a substantial fraction (20-30%) of patients progress to advanced stages – usually with a grave prognosis. Early differentiation between indolent and aggressive types of MF is important for the choice of treatment regimen and monitoring of the individual patient. Good biomarkers are therefore desired.MethodsHere, we used spatial transcriptomics on skin samples at time-of-diagnosis to enable prediction of patients who later progressed to advanced stages of MF. Formalin-fixed, paraffin-embedded skin biopsies at time of diagnosis from six patients with MF who progressed to advanced stages of disease within 4 months to 12 years after diagnosis, and nine patients who remained in early-stage disease over 9 to 27 years were analyzed using the GeoMx Digital Spatial Profiler to capture spatially resolved high-plex RNA gene expression data. Five different regions of interest (the epidermis, the basal layer of epidermis, CD4+ T-cells and neighboring cells, and Pautrier’s microabscesses) were profiled for further assessment.Results and discussionInterestingly, RUNX2, SHMT2, and MCM7 were upregulated in the enriched population of malignant T-cells in Pautrier’s microabscesses in patients who later developed advanced stages of disease. Expression of RUNX2, SHMT2 and MCM7 in malignant T-cells was confirmed in a subset of patients in MF skin using scRNA-seq datasets across multiple studies and correlating with stage of disease. Taken together, we provide first evidence that RUNX2 has potential as a biomarker to identify MF patients progressing to advanced stage disease. As RUNX2 has not previously been linked to MF, our data also shows the analytical strength of combining spatial transcriptomics with scRNA-seq analysis.
SGLT2i and GLP1-RA exert additive cardiorenal protection with a RAS blocker in uninephrectomized db/db mice
Authors: Martos-Guillami Nerea , Vergara Ander , Llorens-Cebrià Carmen , Motto Aku Enam , Martínez-Díaz Irene , Gonçalves Francisco , Garcias-Ramis Maria Magdalena , Allo-Urzainqui Estibaliz , Narváez Alonso , Bermejo Sheila , Muñoz Vicent , León-Román Juan , Ferrer-Costa Roser , Jacobs-Cachá Conxita , Vilardell-Vilà Jordi , Soler María José 
Published: October 2024

IntroductionDiabetic Kidney Disease (DKD) is the main cause of end-stage renal disease in the developed world. The current treatment of the DKD with renin-angiotensin system (RAS) blockade does not totally halt the progression to end stage kidney disease. Currently, several drugs have shown to delay DKD progression such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like-1 receptor agonists (GLP-1RA). We hypothesized that by combining several drugs that prevent DKD progression on top of RAS blockade a synergistic effect would be achieved in terms of cardiorenal protection. In the present study, we analysed if the combination of a RAS blocker (ramipril) with a SGLT2i (empagliflozin) and/or GLP-1RA (semaglutide) in a type 2 diabetic mouse model could have add-on effects in kidney and heart protection.MethodsMale and female uninephrectomized type 2 diabetic db/db mice were treated with empagliflozin and/or semaglutide on top of ramipril during 8 weeks. During the study body weight, water and food intake were weekly monitored, glycaemia biweekly and albuminuria and glomerular filtration rate (GFR) before and after the treatment. At the end of the experiment, kidney and heart were isolated for histological and gene expression studies as well as for intrarenal RAS state assessment.ResultsSemaglutide combined with ramipril and/or empagliflozin significantly decreased albuminuria but only when combined with both compounds, semaglutide further decreased blood glucose, glomerular hyperfiltration in male mice and glomerular mesangial matrix expansion. In kidney, only the triple treatment with empagliflozin, semaglutide and ramipril reduced the expression of the proinflammatory and profibrotic genes ccl2 and TGFß1. In addition, the combination of empagliflozin and semaglutide on top of RAS blockade was superior in decreasing cardiomyocyte hypertrophy and heart fibrosis in db/db mice.DiscussionOur results suggest that the combination of SGLT2i with GLP-1RA is superior in cardiorenal protection in DKD than the drugs administered alone on top of RAS blockade.
Dimerization and lysine substitution of melittin have differing effects on bacteria
Authors: Matthyssen Tamara , Li Wenyi , Holden James A. , Lenzo Jason C. , Hadjigol Sara , O’Brien-Simpson Neil M. 
Published: October 2024

IntroductionMelittin is a potent antimicrobial peptide from bee venom that is effective against both Gram-positive and Gram-negative bacteria. However, it is extremely toxic to mammalian cells and, as yet, has no clinical use. Modifications to its amino acid sequence, cyclization, truncation, and dimerization have been attempted in order to reduce its toxicity whilst maintaining its antimicrobial activity.MethodsIn this study, we targeted the three lysine residues present in melittin and substituted them with lysine homologs containing shorter side chains (ornithine, Orn, diaminobutyric acid, Dab, and diaminopropanoic acid, Dap) and made both parallel and antiparallel melittin dimers to observe how lysine substitution and dimerization affects its activity and toxicity. The antibacterial activity of melittin and its analogs was tested against S. aureus (Gram-positive bacteria) and E. coli (Gram-negative bacteria), and cytotoxicity was tested against the mammalian cell lines HEK293 and H4IIE.ResultsOverall, dimerization and lysine substitution exhibited improved antimicrobial activity toward E. coli and limited improvement toward S. aureus. However, mammalian cell toxicity was only marginally reduced compared to native melittin. Interestingly, the parallel dimer was found to be marginally more active than the antiparallel dimer, indicating orientation maybe important for activity, although both dimers were less effective than the native and Lys-analog peptides toward S. aureus. Of the Lys substitutions, Dab and Dap improved melittin’s activity toward E. coli.DiscussionDimerization and Lys substitution of melittin improved the antimicrobial activity toward Gram-negative bacteria but did not significantly improve its activity toward Gram-positive bacteria. Some analogs also displayed reduced toxicity toward HEK293 and H4IIE cells but overall remained toxic at bactericidal concentrations. Our data indicates that although highly antibacterial, melittin’s toxicity is the major drawback in its potential use.
Elevated peripheral glutamate and upregulated expression of NMDA receptor NR1 subunit in insomnia disorder
Authors: Lin Jingjing , Hou Xiaohui , Liu Yaxi , Cai Yixian , Pan Jiyang , Liao Jiwu 
Published: October 2024

BackgroundThe present study explored the serum glutamate (Glu), glutamine (Gln), glutamic acid dehydrogenase (GAD) concentrations and the mRNA expression levels of the N-methyl-D-aspartate receptor (NMDAR) NR1 subunit in the peripheral blood of patients with insomnia disorder (ID). To our knowledge, this is the first study showing an increase in the mRNA expression levels of the NMDAR NR1 subunit in patients with ID.MethodsThis study included 30 ID patients and 30 matched healthy controls. We investigated the demographic and illness information and assessed subjective sleep quality using the Pittsburgh Sleep Quality Index. The Hamilton Depression Scale-17 and Hamilton Anxiety Scale were used to evaluate the patients’ symptoms of depression and anxiety, respectively. The quantifications of Glu, Gln and GAD concentrations were performed by Enzyme-linked immunosorbent assay (ELISA). Real-time PCR was used to detect the mRNA expression levels of the NMDAR NR1 subunit in peripheral blood.ResultsCompared with the healthy control group, the serum Glu concentrations and the mRNA expression levels of the NMDAR NR1 subunit in the ID group were significantly higher. However, there was no significant difference in Gln and GAD between the two groups. The receiver operating characteristic (ROC) analysis showed that the mRNA expression levels of the NMDAR NR1 subunit could distinguish ID patients from healthy individuals (area under the curve: 0.758; sensitivity: 73.3%; specificity: 76.7%). A negative correlation was found between the mRNA expression levels of the NMDAR NR1 subunit for age, total duration of illness, and age of first onset in the ID group, whereas a positive correlation was detected for daytime dysfunction.ConclusionGlutamatergic neurotransmission was abnormal in ID patients. Additionally, the mRNA expression levels of the NMDAR NR1 subunit appeared to have potential as a clinical biomarker for ID. However, the sample size of our study was limited, and future studies with larger sample sizes are needed to further validate and explore the mechanisms involved and to assess the reliability of the biomarker.
Estimating the benefit of esketamine nasal spray versus real-world treatment on patient-reported functional remission: results from the ICEBERG study
Authors: Oliveira-Maia Albino J. , Rive Benoît , Godinov Yordan , Mulhern-Haughey Siobhán 
Published: October 2024

IntroductionTreatment resistant depression (TRD) affects approximately 10–30% of patients with major depressive disorder, and most patients with TRD do not respond to real-world treatments (RWT). Treatment with esketamine nasal spray (NS) plus a selective serotonin or serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) has significant long-term clinical benefit over RWT in patients with TRD. However, the impact on patient-reported function remains to be determined.MethodsThe ICEBERG analysis was an indirect treatment comparison performed using data from two studies of patients with TRD: SUSTAIN-2 (esketamine NS; NCT02497287) and the European Observational TRD Cohort (EOTC; RWT; NCT03373253; clinicaltrials.gov). Here, patient−reported functional remission, assessed using the Sheehan Disability Scale (SDS), was defined as SDS ≤6 at Month 6. Analyses were conducted using propensity score re−weighting and multivariable models based on 18 covariates.ResultsAt Month 6, the probability of functional remission in esketamine NS−treated patients from SUSTAIN-2 (n=512) was 25.6% (95% confidence interval [CI] 21.8–29.4), while the adjusted probability for RWT patients from the EOTC (n=184) was 11.5% (95% CI 6.9–16.1; relative risk: 2.226 [95% CI 1.451–3.416]; p=0.0003). In the total combined population (N=696), patients who did not achieve clinical response or remission had a low probability of achieving functional remission (5.84% and 8.76%, respectively). However, for patients who did achieve clinical response or remission, the probability of achieving functional remission was greater (43.38% and 54.15%, respectively), although many still did not achieve this status.ConclusionsFor patients with TRD, esketamine NS had a significant functional benefit versus RWT after 6 months of treatment. Irrespective of treatment, achievement of clinical response or remission was insufficient to attain functional remission. Nevertheless, clinical remission increased the likelihood of achieving functional remission, further supporting an important role for clinical remission in for the path towards functional recovery.
Do reusables pose greater infectious risks than disposables for consumer goods? A systematic literature review
Authors: Ira Sanjidah Ahmed , Sherry Brooke Elise , Amin Ruhana , Abdul-Hamid Ma-sum , Roberts Timothy , Hochman Sarah , Thiel Cassandra L. 
Published: October 2024

Increased concern over climate change and the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus resulted in a clash of political directives around reusable and disposable food serviceware. Decreasing single-use items will likely reduce consumption and environmental emissions; however, improper cleaning of reusable items could result in greater risks of disease transmission. We sought to assess the risks of reusable and disposable food serviceware and document disinfection protocols by conducting a systematic literature review of articles that assessed materials or products that could be fomites to specific food-borne pathogens. After initial screening, the study team extracted data from 122 articles. The most common pathogens studied were E. coli (25% of included studies), general bacteria (24%), and Norovirus (16%). Thirteen studies (8%) focused on SARS-CoV-2. A majority of studies analyzed plastics (27%), stainless steel (22%), or porous surfaces such as paper and cardboard (12%). Forty seven of the studies (35%) were conducted in a food service setting, and 40 studies (30%) tested disinfection techniques. Despite a large body of related literature, there is very little evidence suggesting that either reusable or disposable food serviceware is safer for minimizing infectious risks. Pathogens can survive on various fomites, though greater surface porosity and higher humidity levels increase viability of most pathogens. There appear to be no major differences in pathogen viability on various fomites. There is a paucity of research that can specifically aid in developing policy or guidelines for appropriate use of reusable food serviceware. Though given recent studies on SARS-CoV-2, banning reusable bags and food serviceware is an inappropriate response to this particular pathogen, which is rarely spread through surface contact. Further research is needed that explicitly studies pathogen viability, transmission risks, and appropriate disinfection techniques for disposable and reusable food serviceware in order to devise effective sustainability policies.
INFRAESTRUTURA VERDE EM INSTITUIÇÕES DE EDUCAÇÃO INFANTIL
Authors: Oliveira Alesandra Rafael de 
Published: October 2024

Este artigo objetiva analisar a infraestrutura verde de quatro unidades de Educação Infantil localizadas em Curitiba/PR. Por meio de mapeamento geográfico através de sistema de geoprocessamento, intenta-se identificar a existência de diferenças estruturais no que diz respeito ao espaço destinado às áreas verdes presentes nas primeiras unidades inauguradas na cidade, se comparadas às unidades educativas inauguradas recentemente. Essa pesquisa apresenta uma abordagem qualitativa de natureza exploratória e interpretativa, fundamentada na Dimensão Institucional, proposta por Vainer et al., (2012). Concluímos que as políticas públicas de infra-estrutura na cidade de Curitiba, têm proporcionado mudanças sociais e ambientais, ampliando gradativamente os espaços verdes em suas instituições educativas.
ЛЕСНАЯ БИОЭКОНОМИКА И УСТОЙЧИВОЕ УПРАВЛЕНИЕ ЛЕСАМИ. АГРОЛЕСОВОДСТВО
Authors: МУРАВЬЕВА М.А. , НАЗАРОВА О.Г. 
Published: October 2024

Основная задача человеческого общества на данном этапе развития заключается в поиске рационального и максимально устойчивого способа существования, производства и потребления. Хозяйствующие субъекты все больше обращают внимание на разработку таких внутренних и внешних стратегий своего развития, которые имеют «зеленое» направление. В связи с этим в данной статье нами рассматриваются вопросы и проблемы лесной биоэкономики как объекта маркетинга, связанные с развитием такого направления, как агролесоводство. Предлагаются пути решения представленных проблем. Агролесоводство представляет собой совокупный подход, использующий все те преимущества, которые можно получить, если совместить деревья и кусты с культурами сельскохозяйственного назначения и (или) домашним скотом. Рассматриваемый подход включает не только сельскохозяйственные, но и лесоводческие технологии, которые в совокупности создаст более разнообразные, благотворные, рентабельные, продуктивные и устойчивые системы по использованию земельных ресурсов. Перед методами лесоводства и сельского хозяйства, которые относятся к традиционным, методы, применяемые в агролесоводстве, несомненно имеют определённые преимущества. Их использование подразумевает повышенную продуктивность, экономическую выгоду и большое разнообразие экологической продукции, а, следовательно, являются элементами устойчивого управления лесами.
The main task of human society at this stage of development is to find a rational and most sustainable way of existence, production and consumption. Business entities are increasingly paying attention to the development of such internal and external strategies for their development, which have a "green" direction. In this regard, in this article we consider the issues and problems of forest bioeconomics as an object of marketing related to the development of such a direction as agroforestry. Ways of solving the presented problems are proposed. Agroforestry is a holistic approach, utilizing all the benefits that can be gained by combining trees and shrubs with crops and/or livestock. The approach under consideration includes not only agricultural but also forestry technologies, which together will create more diverse, beneficial, cost-effective, productive and sustainable systems for the use of land resources. Over traditional forestry and agricultural methods, agroforestry methods undoubtedly have certain advantages. Their use implies increased productivity, economic benefits and a wide variety of ecological products, and, therefore, are elements of sustainable forest management.