bluuebunny/crossref_metadata_2025 huggingface dataset:
Políticas públicas na pandemia: análise bibliométrica no contexto brasileiro na Web of Science e Scopus
Authors: Sarmiento Ramírez Yunier , Guzmán del Rio Daniel , Hechavarria Pérez José Ramón , Pérez Cutiño Yadira , Scoralick William , Rocha Igor de Oliveira
Published: September 2021

A pandemia do Corona Vírus trouxe sérios problemas de ordem mundial, que implicam nas mais variadas atividades da sociedade causando desordem e aumento da entropia social. Nesse sentido, governos e instituições têm implementado políticas públicas com o objetivo de minimizar os impactos da doença e, simultaneamente, essas experiências têm gerado um aumento na produção científica sobre o assunto. Portanto, o objetivo deste trabalho é mostrar a relevância acadêmica das produções científicas sobre políticas públicas na pandemia por meio de uma análise bibliométrica. O estudo foi realizado nas bases de dados Web of Science e Scopus. Possibilitou a construção de um portfólio bibliográfico com 39 artigos relevantes e alinhados ao tema. Além dos artigos selecionados que servem de referencial teórico sobre o tema em questão, destacam-se as produções científicas mais relevantes a partir do InOrdinatio, que considera o fator de impacto, número de citações e o ano de publicação. O estudo também usa a análise de cluster como técnica de classificação multivariada e o software VOSviewer para mapeamento bibliográfico.
Seasonal dispersal of gammaridean amphipods away from Sargassum beds in relation to macroalgal host defoliation
Authors: Kodama M , Hayakawa J , Oba S , Kawamura T
Published: September 2021

Epibenthic invertebrate assemblages in macroalgal beds generally show remarkable seasonal fluctuations in abundance and species composition, reflecting macroalgal host growth and defoliation. Notably, they often drastically decrease during macroalgal host defoliation. Though this reduction has been explained in terms of dispersal away from the macroalgal bed in relation to macroalgal host defoliation, this hypothesis has not previously been experimentally detailed. We conducted a field experiment using an imitation of Sargassum that was set 1 m away from a Sargassum yezoense bed to examine whether the epibenthic gammarids disperse away from the Sargassum bed as a result of Sargassum defoliation. The imitations were replaced monthly throughout the Sargassum defoliation season; subsequently, gammarids associated with the imitation (assumed as migrants from the Sargassum beds) as well as the gammarids that occurred in the Sargassum bed were investigated. Seasonal patterns of gammarid abundance in the Sargassum bed and their dispersal to the imitations were found to be quite different among gammarid species. In particular, 2 dominant gammarids, the suspension-feeding Jassa morinoi and Podocerus sp., drastically decreased in the Sargassum bed and coincidently increased in the imitations during the Sargassum defoliation season, indicating their defoliation-associated dispersal from the Sargassum bed. This is the first field experimental study demonstrating the defoliation-associated dispersal of epibenthic invertebrates in macroalgal beds. The dispersal is likely caused by a reduction of habitat space and quality due to thalli defoliation. Since many macroalgae show seasonal growth and defoliation, the concept of defoliation-associated dispersal is potentially applicable to various macroalgal species.
Simulating fish population responses to elevated CO2: a case study using winter flounder
Authors: Huebert KB , Rose KA , Chambers RC
Published: September 2021

Scaling experimentally derived effects of CO2 on marine fauna to population responses is critical for informing management about potential ecological ramifications of ocean acidification. We used an individual-based model of winter flounder to extrapolate laboratory-derived effects of elevated CO2 assumed for early life stages of fish to long-term population dynamics. An offspring module with detailed hourly to daily representations of spawning, growth, and mortality that incorporates potential elevated CO2 effects was linked to an annual time-step parent module. We calibrated the model using a 40 yr Reference simulation (1977-2016) that included gradual warming and then performed ‘Retrospective’ simulations that assumed a suite of elevated CO2 effects by changing fertilization rate, mortality rate of embryos due to developmental malformations, larval growth rate, and size-at-settlement. ‘Recovery’ simulations that started at low population size were then used to further explore possible interactions between the effects of CO2 and warming on population productivity. Warming had a major negative effect on the simulated winter flounder population abundance, and reduced larval growth had the largest single impact among the CO2 effects tested. When a combination of the assumed CO2 effects was imposed together, average annual recruitment and spawning stock biomass were reduced by half. In the Recovery simulations, inclusion of CO2 effects amplified the progressive decrease in population productivity with warming. Our analysis is speculative and a first step towards addressing the need for extrapolating from laboratory effects of ocean acidification to broader, ecologically relevant scales.
Working with dairy farmers to improve their pasture management skills through better understanding the principles of ryegrass growth
Authors: Clarke Brian , Donaghy Danny , Casey Marie
Published: September 2021

The relationships between leaf regrowth stage, pre- and post-grazing pasture covers, and grazing rotation length are complex. Despite the existence of well-documented grazing guidelines for managing these relationships, implementation on-farm is highly variable indicating that skill levels are often inadequate and/or farmers are not convinced of the benefits. Twenty dairy farm managers and assistant managers from the Hopkins Farming Group in the lower North Island engaged in structured observation and discussion with experts to test the potential of the 3-leaf grazing technique for increasing pasture production and reducing imported supplement use from mid-spring to mid-autumn. The farmer members of the study group initially had little knowledge of the principles of ryegrass growth at the plant level, and how their management influences pasture production and persistence. Grazing management skills developed by group members during the process included: identification of pasture species within the sward, including perennial ryegrass; identification of leaf morphology, tillers, tiller buds and daughter tillers; pasture health checks to understand when new tillers appeared and their grazing and nutrient needs; and the importance of grazing residuals for future pasture quality. Pasture productivity, as measured by the amount of silage conserved, increased by approximately 0.45 t DM/ha during the 6 months of study through the application of this grazing management technique. Managing grazing using the 3-leaf technique requires a greater depth of knowledge than previous, simple, rotation length-based systems. Many farmers are concerned about the lack of persistence of new ryegrass cultivars, whereas it may be their management practices that have a greater influence.
Aesthetic Expression dalam Praktik Keperawatan
Authors: Rustam Junaidy Suparman
Published: September 2021

Aesthetic expression adalah hubungan yang unik antara pasien dan perawat dengan melakukan tindakan kepedulian yang berdasarkan pada pengalaman hidup, keyakinan individu, pengembangan diri, dan memungkinkan perawat dapat melihat dan mengintegrasikan diri mereka ke semua tindakan asuhan keperawatan. Studi ini merupakan tradisional literatur review yang bertujuan untuk mengeksplore penerapan aesthetic expression dalam praktek keperawatan. Kriteria inklusi pada studi literatur ini antara lain; jurnal yang membahas tentang bentuk penerapan aesthetic expression dalam praktek keperawatan, artikel bebahasa Inggris dan Indonesia, artikel terbitan tahun 2009-2020. Strategi penelusuran literatur review ini dilakukan dengan mengakses beberapa data base seperti Proquest, CINAHL, Elsevier/Science Direct, Pubmed, dan Google Schoolar dengan menggunakan kata kunci aesthetic, aesthetic expression, nursing care, nursing practice, estetika dan praktik keperawatan, Hasil dari literatur review menemukan beberapa bentuk penerapan asthetic expression dalam praktek keperawatan meliputi terapi music,terapi dance, puisi, humor, dan visual. Studi selanjutnya diharapkan dapat mengembangkan penelitian tentang penerapan aesthetic expression khususnya pada spesifikasi bidang dalam praktek keperawatan.
Exploring the Potential of Corynebacterium glutamicum to Produce the Compatible Solute Mannosylglycerate
Authors: Schwentner Andreas , Neugebauer Heiko , Weinmann Serin , Santos Helena , Eikmanns Bernhard J.
Published: September 2021

The compatible solute mannosylglycerate (MG) has exceptional properties in terms of protein stabilization and protection under salt, heat, and freeze-drying stresses as well as against protein aggregation. Due to these characteristics, MG possesses large potential for clinical and biotechnological applications. To achieve efficient MG production, Corynebacterium glutamicum was equipped with a bifunctional MG synthase (encoded by mgsD and catalyzing the condensation of 3-phosphoglycerate and GDP-mannose to MG) from Dehalococcoides mccartyi. The resulting strain C. glutamicum (pEKEx3 mgsD) intracellularly accumulated about 111 mM MG (60 ± 9 mg gCDW−1) with 2% glucose as a carbon source. To enable efficient mannose metabolization, the native manA gene, encoding mannose 6-phosphate isomerase, was overexpressed. Combined overexpression of manA and mgsD from two plasmids in C. glutamicum resulted in intracellular MG accumulation of up to ca. 329 mM [corresponding to 177 mg g cell dry weight (CDW)−1] with glucose, 314 mM (168 mg gCDW−1) with glucose plus mannose, and 328 mM (176 mg gCDW−1) with mannose as carbon source(s), respectively. The product was successfully extracted from cells by using a cold water shock, resulting in up to 5.5 mM MG (1.48 g L−1) in supernatants. The two-plasmid system was improved by integrating the mgsD gene into the manA-bearing plasmid and the resulting strain showed comparable production but faster growth. Repeated cycles of growth/production and extraction of MG in a bacterial milking-like experiment showed that cells could be recycled, which led to a cumulative MG production of 19.9 mM (5.34 g L−1). The results show that the newly constructed C. glutamicum strain produces MG from glucose and mannose and that a cold water shock enables extraction of MG from the cytosol into the medium.
SALL1 Modulates CBX4 Stability, Nuclear Bodies, and Regulation of Target Genes
Authors: Giordano Immacolata , Pirone Lucia , Muratore Veronica , Landaluze Eukene , Pérez Coralia , Lang Valerie , Garde-Lapido Elisa , Gonzalez-Lopez Monika , Barroso-Gomila Orhi , Vertegaal Alfred C. O. , Aransay Ana M. , Rodriguez Jose Antonio , Rodriguez Manuel S. , Sutherland James D. , Barrio Rosa
Published: September 2021

Development is orchestrated through a complex interplay of multiple transcription factors. The comprehension of this interplay will help us to understand developmental processes. Here we analyze the relationship between two key transcription factors: CBX4, a member of the Polycomb Repressive Complex 1 (PRC1), and SALL1, a member of the Spalt-like family with important roles in embryogenesis and limb development. Both proteins localize to nuclear bodies and are modified by the small ubiquitin-like modifier (SUMO). Our results show that CBX4 and SALL1 interact in the nucleoplasm and that increased SALL1 expression reduces ubiquitination of CBX4, enhancing its stability. This is accompanied by an increase in the number and size of CBX4-containing Polycomb bodies, and by a greater repression of CBX4 target genes. Thus, our findings uncover a new way of SALL1-mediated regulation of Polycomb bodies through modulation of CBX4 stability, with consequences in the regulation of its target genes, which could have an impact in cell differentiation and development.
Natural Drug-Loaded Bimetal-Substituted Hydroxyapatite-Polymeric Composite for Osteosarcoma-Affected Bone Repair
Authors: Wang Yanjun , Yao Yongfeng , Thirumurugan Muthupandi , Prabakaran Selvakani , Rajan Mariappan , Wang Kai
Published: September 2021

Repairing segmental bone deformities after resection of dangerous bone tumors is a long-standing clinical issue. The study’s main objective is to synthesize a natural bioactive compound-loaded bimetal-substituted hydroxyapatite (BM-HA)-based composite for bone regeneration. The bimetal (copper and cadmium)-substituted HAs were prepared by the sol-gel method and reinforced with biocompatible polyacrylamide (BM-HA/PAA). Umbelliferone (UMB) drug was added to the BM-HA/PAA composite to enhance anticancer activity further. The composite’s formation was confirmed by various physicochemical investigations, such as FT-IR, XRD, SEM, EDAX, and HR-TEM techniques. The bioactivity was assessed by immersing the sample in simulated body fluid for 1, 3, and 7 days. The zeta potential values of BM-HA/PAA and BM-HA/PAA/UMB are −36.4 mV and −49.4 mV, respectively. The in vitro viability of the prepared composites was examined in mesenchymal stem cells (MSCs). It shows the ability of the composite to produce osteogenic bone regeneration without any adverse effects. From the gene expression and PCR results, the final UMB-loaded composite induced osteogenic markers, such as Runx, OCN, and VEFG. The prepared bimetal substituted polyacrylamide reinforced HA composite loaded with UMB drug has the ability for bone repair/regenerations.
The Conformationally Sensitive Spatial Distance Between the TM3-4 Loop and Transmembrane Segment 7 in the Glutamate Transporter Revealed by Paired-Cysteine Mutagenesis
Authors: Qu Qi , Wang Ji , Li Guiping , Chen Rongqing , Qu Shaogang
Published: September 2021

Excitatory amino acid transporters can maintain extracellular glutamate concentrations lower than neurotoxic levels by transferring neurotransmitters from the synaptic cleft into surrounding glial cells and neurons. Previous work regarding the structural studies of GltPh, GltTK, excitatory amino acid transporter 1 (EAAT1), EAAT3 and alanine serine cysteine transporter 2 described the transport mechanism of the glutamate transporter in depth. However, much remains unknown about the role of the loop between transmembrane segment 3 and 4 during transport. To probe the function of this loop in the transport cycle, we engineered a pair of cysteine residues between the TM3-TM4 loop and TM7 in cysteine-less EAAT2. Here, we show that the oxidative cross-linking reagent CuPh inhibits transport activity of the paired mutant L149C/M414C, whereas DTT inhibits the effect of CuPh on transport activity of L149C/M414C. Additionally, we show that the effect of cross-linking in the mutant is due to the formation of the disulfide bond within the molecules of EAAT2. Further, L-glutamate or KCl protect, and D,L-threo-β-benzyloxy-aspartate (TBOA) increases, CuPh-induced inhibition in the L149C/M414 mutant, suggesting that the L149C and M414C cysteines are closer or farther away in the outward- or inward-facing conformations, respectively. Together, our findings provide evidence that the distance between TM3-TM4 loop and TM7 alter when substrates are transported.
Transcriptional Activity of Predominant Streptococcus Species at Multiple Oral Sites Associate With Periodontal Status
Authors: Belstrøm Daniel , Constancias Florentin , Markvart Merete , Sikora Martin , Sørensen Christiane Elisabeth , Givskov Michael
Published: September 2021

Background

Streptococcus species are predominant members of the oral microbiota in both health and diseased conditions. The purpose of the present study was to explore if different ecological characteristics, such as oxygen availability and presence of periodontitis, associates with transcriptional activity of predominant members of genus Streptococcus. We tested the hypothesis that genetically closely related Streptococcus species express different transcriptional activities in samples collected from environments with critically different ecological conditions determined by site and inflammatory status.

Methods

Metagenomic and metatranscriptomic data was retrieved from 66 oral samples, subgingival plaque (n=22), tongue scrapings (n=22) and stimulated saliva (n=22) collected from patients with periodontitis (n=11) and orally healthy individuals (n=11). Species-specific transcriptional activity was computed as Log2(RNA/DNA), and transcriptional activity of predominant Streptococcus species was compared between multiple samples collected from different sites in the same individual, and between individuals with different oral health status.

Results

The predominant Streptococcus species were identified with a site-specific colonization pattern of the tongue and the subgingival plaque. A total of 11, 4 and 2 pathways expressed by S. parasanguinis, S. infantis and S. salivarius, respectively, were recorded with significantly higher transcriptional activity in saliva than in tongue biofilm in healthy individuals. In addition, 18 pathways, including pathways involved in synthesis of peptidoglycan, amino acid biosynthesis, glycolysis and purine nucleotide biosynthesis expressed by S. parasanguinis and 3 pathways expressed by S. salivarius were identified with significantly less transcriptional activity in patients with periodontitis.

Conclusion

Data from the present study significantly demonstrates the association of site-specific ecological conditions and presence of periodontitis with transcriptional activity of the predominant Streptococcus species of the oral microbiota. In particular, pathways expressed by S. parasanguinis being involved in peptidoglycan, amino acid biosynthesis, glycolysis, and purine nucleotide biosynthesis were identified to be significantly associated with oral site and/or inflammation status.
The Exosomal lncRNA KLF3-AS1 From Ischemic Cardiomyocytes Mediates IGF-1 Secretion by MSCs to Rescue Myocardial Ischemia-Reperfusion Injury
Authors: Chen Gecai , Yue Aihuan , Wang Meixiang , Ruan Zhongbao , Zhu Li
Published: September 2021

The purpose of the study was to explore the mechanism by which myocardial ischemia-reperfusion (I/R) injury-induced exosomes modulate mesenchymal stem cells (MSCs) to regulate myocardial injury. In this study, we established an I/R injury model in vivo and a hypoxia-reoxygenation (H/R) model in vitro. Then, exosomes isolated from H/R-exposed H9c2 cells were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot analysis. CCK-8 assays and flow cytometry were performed to assess cell injury. ELISA was applied to determine the level of insulin-like growth factor 1 (IGF-1). Echocardiography was used to assess cardiac function in vivo. HE staining and TUNEL assays were conducted to analyze myocardial injury in vivo. In the present study, H/R-exposed H9c2 cells induced IGF-1 secretion from MSCs to inhibit cell myocardial injury. Moreover, exosomes derived from H/R-exposed H9c2 cells were introduced to MSCs to increase IGF-1 levels. The lncRNA KLF3-AS1 was dramatically upregulated in exosomes derived from H/R-treated H9c2 cells. Functional experiments showed that the exosomal lncRNA KLF3-AS1 promoted IGF-1 secretion from MSCs and increased H9c2 cell viability. In addition, miR-23c contains potential binding sites for both KLF3-AS1 and STAT5B, and miR-23c directly bound to the 3'-UTRs of KLF3-AS1 and STAT5B. Furthermore, the lncRNA KLF3-AS1 promoted IGF-1 secretion from MSCs and rescued myocardial cell injury in vivo and in vitro by upregulating STAT5B expression. The lncRNA KLF3-AS1 may serve as a new direction for the treatment of myocardial I/R injury.
Mycorrhizal Symbiosis for Better Adaptation of Trees to Abiotic Stress Caused by Climate Change in Temperate and Boreal Forests
Authors: Usman Muhammad , Ho-Plágaro Tania , Frank Hannah E. R. , Calvo-Polanco Monica , Gaillard Isabelle , Garcia Kevin , Zimmermann Sabine D.
Published: September 2021

Global climate changes have serious consequences on natural ecosystems and cause diverse environmental abiotic stressors that negatively affect plant growth and development. Trees are dependent on their symbiosis with mycorrhizal fungi, as the hyphal network significantly improves the uptake of water and essential mineral nutrients by colonized roots. A number of recent studies has enhanced our knowledge on the functions of mycorrhizal associations between fungi and plant roots. Moreover, a series of timely studies have investigated the impact and benefit of root symbioses on the adaptation of plants to climate change-associated stressors. Trees in temperate and boreal forests are increasingly exposed to adverse environmental conditions, thus affecting their durable growth. In this mini-review, we focus our attention on the role mycorrhizal symbioses play in attenuating abiotic stressors imposed on trees facing climatic changes, such as high temperatures, drought, salinity, and flooding.
MAT2A-Mediated S-Adenosylmethionine Level in CD4+ T Cells Regulates HIV-1 Latent Infection
Authors: Yang Xiaofan , Huang Ting , Wang Tiantian , Gao Hongbo , Zhang Haitao , Peng Wen , Zhao Jiacong , Hu Shujing , Lu Panpan , Hong Zhongsi , Li Bo , Deng Kai
Published: September 2021

Antiretroviral drugs effectively halt HIV-1 replication and disease progression, however, due to the presence of a stable viral latent reservoir, the infection cannot be cured by antiretroviral drugs alone. Elucidating the molecular mechanisms underlying HIV-1 latent infection remains a critical hurdle that precludes the development of novel therapeutic strategies aiming for a potential functional cure. Cellular metabolism has been reported to affect HIV-1 replication in CD4+ T cells, but it remains largely unclear whether it is involved in the regulation of HIV-1 latency. Here, we performed a sub-pooled CRISPR library knockout screen targeting 1773 metabolic-related genes in a cell model of HIV-1 latent infection and found that Methionine Adenosyltransferase 2A (MAT2A) contributes to HIV-1 latency. MAT2A knockout enhanced the reactivation of latent HIV-1 while MAT2A overexpression did the opposite. Mechanistically, MAT2A modulates HIV-1 latency through S-Adenosylmethionine (SAM)-mediated one-carbon flux. MAT2A knockout resulted in a significant downregulation of DNA and histone methylation at the HIV-1 5’-LTR. Importantly, we found that the plasma level of SAM is positively correlated with HIV-1 DNA in PBMCs from ART-treated infected individuals, suggesting SAM could serve as a potential biomarker for the latent viral reservoir. Overall, this study reveals an important role of MAT2A-mediated one-carbon metabolism in regulating HIV-1 latency and provides a promising target for the development of new strategies for a functional cure of HIV-1.
Phosphorus Dynamics Associated With Organic Carbon Mineralization by Reduction of Sulfate and Iron in Sediment Exposed to Fish Farming
Authors: Mok Jin-Sook , Choi Ayeon , Kim Bomina , An Sung-Uk , Lee Won-Chan , Kim Hyung Chul , Kim Jonguk , Yoon Cheolho , Hyun Jung-Ho
Published: September 2021

The expansion of the aquaculture industry has resulted in accumulation of phosphorus (P)-rich organic matter via uneaten fish feed. To elucidate the impact of fish farming on P dynamics, P speciation, and benthic P release along with partitioning of organic carbon (Corg) mineralization coupled to sulfate reduction (SR) and iron reduction (FeR) were investigated in the sediments from Jinju Bay, off the southern coast of South Korea, in July 2013. SR in the farm sediment was 6.9-fold higher than the control sediment, and depth-integrated (0–10 cm) concentrations of NH4+, PO43–, and H2S in pore water of the farm sediment were 2.2-, 3.3-, and 7.4-fold higher than that in control sediment, respectively. High biogenic-P that comprised 28% of total P directly reflected the impact of P-rich fish feed, which ultimately enhanced the bioavailability (58% of total P) of P in the surface sediment of the farm site. In the farm sediment where SR dominated Corg mineralization, H2S oxidation coupled to the reduction of FeOOH stimulated release of P bound to iron oxide, which resulted in high regeneration efficiency (85%) of P in farm sediments. Enhanced P desorption from FeOOH was responsible for the increase in authigenic-P and benthic P flux. Authigenic-P comprised 33% of total P, and benthic P flux to the overlying water column accounted for approximately 800% of the P required for primary production. Consequently, excessive benthic P release resulting directly from oversupply of P-rich fish feed was a significant internal source of P for the water column, and may induce undesirable eutrophication and harmful algal blooms in shallow coastal ecosystems.
Comparison of Cell Wall Polysaccharide Composition and Structure Between Strains of Sporothrix schenckii and Sporothrix brasiliensis
Authors: Villalobos-Duno Héctor L. , Barreto Laura A. , Alvarez-Aular Álvaro , Mora-Montes Héctor M. , Lozoya-Pérez Nancy E. , Franco Bernardo , Lopes-Bezerra Leila M. , Niño-Vega Gustavo A.
Published: September 2021

Sporothrix schenckii, Sporothrix brasiliensis, and Sporothrix globosa are the main causative agents of sporotrichosis, a human subcutaneous mycosis. Differences in virulence patterns are associated with each species but remain largely uncharacterized. The S. schenckii and S. brasiliensis cell wall composition and virulence are influenced by the culturing media, with little or no influence on S. globosa. By keeping constant the culturing media, we compared the cell wall composition of three S. schenckii and two S. brasiliensis strains, previously described as presenting different virulence levels on a murine model of infection. The cell wall composition of the five Sporothrix spp. strains correlated with the biochemical composition of the cell wall previously reported for the species. However, the rhamnose-to-β-glucan ratio exhibits differences among strains, with an increase in cell wall rhamnose-to-β-glucan ratio as their virulence increased. This relationship can be expressed mathematically, which could be an important tool for the determination of virulence in Sporothrix spp. Also, structural differences in rhamnomannan were found, with longer side chains present in strains with lower virulence reported for both species here studied, adding insight to the importance of this polysaccharide in the pathogenic process of these fungi.
Prognostic Effect of Microenvironment Phenotype in Triple-Negative Breast Cancer: Biomarker Analysis of a Prospective Trial
Authors: Zhu Si-Yuan , Ma Ding , Shao Zhi-Ming , Yu Ke-Da
Published: September 2021

Background: The microenvironment of triple-negative breast cancer (TNBC) can be divided into three clusters based on bioinformatics-based immunogenomic analysis: the “immune-desert” cluster, the “innate immune-inactivated” cluster, and the “immune-inflamed” cluster. The immune-inflamed cluster is considered as “hot tumor” while the other two are considered as “cold tumor”.

Methods: To investigate the prognostic effect of microenvironment phenotypes on TNBC, we compared relapse-free survival (RFS) of different phenotypes in 100 patients with RNA sequencing-based expression data from the PATTERN trial (NCT01216111, published in JAMA Oncol 2020), which indicated a superior efficacy of adjuvant paclitaxel-plus-carboplatin regimen compared to the regimen of cyclophosphamide/epirubicin/fluorouracil followed by docetaxel for TNBC. We also analyzed the efficacy of the two regimens for different immune phenotypes to explore potential treatment strategies.

Results: No significant difference in RFS was observed between the “hot tumor” and the “cold tumor” (hazard ratio [HR] = 0.68, 95% confidence interval [CI] 0.28–1.66, P = 0.40). However, the “hot tumor” subtype was associated with significantly longer RFS in node-positive patients (HR = 0.27, 95%CI 0.07–0.97, P = 0.03). Consistently, a similar trend to improved RFS of the “hot tumor” phenotype was detected in patients with stage pT2-3 tumors (HR = 0.29, 95%CI 0.06–1.30, P = 0.08). Furthermore, no significant difference in RFS between the two treatment arms was observed in patients with “hot tumor” (HR = 0.39, 95% CI 0.08–2.01, P = 0.24) or “cold tumor” (HR = 1.05, 95% CI 0.39–2.82, P = 0.92).

Conclusion: The microenvironment phenotype in TNBC might have prognostic significance to patients with a high risk of recurrence. The association of the microenvironment phenotypes with the efficacy of adjuvant chemotherapy for TNBC remains to be further studied.
Effect of the COVID-19 Pandemic on Children With SMA Receiving Nusinersen: What Is Missed and What Is Gained?
Authors: Agosto Caterina , Salamon Eleonora , Giacomelli Luca , Papa Simonetta , Benedetti Francesca , Benini Franca
Published: September 2021

Nusinersen is the first oligonucleotide-based drug that is approved for the treatment of spinal muscular atrophy. In January 2020, the WHO declared COVID-19 a pandemic and nusinersen-provider centers had to postpone planned infusions for some children along with other related interventions. Considering the important contribution that the intrathecal infusions and other support activities could have on the quality of life of spinal muscular atrophy patients and their families, this emergency could have a relevant impact on the course of the pathology. The present work aims to assess the clinical and social issues that arise for spinal muscular atrophy children in care at the referral pediatric palliative care Centre of Padua (Veneto) from a delay in nusinersen infusions, resulting from the contingent COVID-19 restrictions. This evaluation has been carried out in both the short and long term after the first lockdown period and can be considered as a “proxy” of a situation of a possible delay in administration or management of infusions, due to other different causes.
Does Modern Lifestyle Favor Neuroimmunometabolic Changes? A Path to Obesity
Authors: Marques Camila Guazzelli , dos Santos Quaresma Marcus V. L. , Nakamoto Fernanda Patti , Magalhães Ana Carolina Oumatu , Lucin Glaice Aparecida , Thomatieli-Santos Ronaldo Vagner
Published: September 2021

Factors linked to modern lifestyles, such as physical inactivity, Western diet, and poor sleep quality have been identified as key contributors to the positive energy balance (PEB). PEB rises adipose tissue hypertrophy and dysfunction over the years, affecting cells and tissues that are metabolically critical for energy homeostasis regulation, especially skeletal muscle, hypothalamic-pituitary-adrenal axis, and gut microbiota. It is known that the interaction among lifestyle factors and tissue metabolic dysfunction increases low-grade chronic systemic inflammation, leading to insulin resistance and other adverse metabolic disorders. Although immunometabolic mechanisms are widely discussed in obesity, neuroimmunoendocrine pathways have gained notoriety, as a link to neuroinflammation and central nervous system disorders. Hypothalamic inflammation has been associated with food intake dysregulation, which comprises homeostatic and non-homeostatic mechanisms, promoting eating behavior changes related to the obesity prevalence. The purpose of this review is to provide an updated and integrated perspective on the effects of Western diet, sleep debt, and physical exercise on the regulation of energy homeostasis and low-grade chronic systemic inflammation. Subsequently, we discuss the intersection between systemic inflammation and neuroinflammation and how it can contribute to energy imbalance, favoring obesity. Finally, we propose a model of interactions between systemic inflammation and neuroinflammation, providing new insights into preventive and therapeutic targets for obesity.
Time-Restricted Feeding and Aerobic Performance in Elite Runners: Ramadan Fasting as a Model
Authors: Al-Nawaiseh Ali M. , Bataineh Mo'ath F. , Kilani Hashem A. , Bellar David M. , Judge Lawrence W.
Published: September 2021

A distance runner's performance is generally limited by energy availability when competing or training. Modifying meal frequency and timing by abstaining from eating or drinking, from dawn to dusk, during Ramadan fasting is hypothesized to induce hypohydration and reduced caloric and nutrient intake. The purpose of this study was to investigate the impact of Ramadan fasting on runners' performances. Fifteen trained male distance runners who observed Ramadan participated in this study (Age = 23.9 ± 3.1 years; Peak VO2 = 71.1 ± 3.4 ml/kg/min). Each participant reported to the human performance lab on two testing occasions (pre-Ramadan and the last week of Ramadan). In each visit, participants performed a graded exercise test on the treadmill (Conconi protocol) and their VO2, Heart Rate, time to exhaustion, RPE, and running speed were recorded. Detailed anthropometrics, food records, and exercise logs were kept for the entire period of the study. Repeated measure ANOVA, paired t-test, and Cohen's effect size analysis were carried out. Results indicated no significant influence for Ramadan fasting on body mass (p = 0.201), body fat (p = 0.488), lean body mass (p = 0.525), VO2max (p = 0.960), energy availability (p = 0.137), and protein intake (p = 0.124). However, carbohydrate (p = 0.026), lipid (p = 0.009), water (p < 0.001), and caloric intakes (p = 0.002) were significantly reduced during Ramadan Fasting. Daily training duration (p < 0.001) and exercise energy expenditure (p = 0.001) were also reduced after Ramadan. Time to exhaustion (p = 0.049), and maximal running speed (p = 0.048) were improved. Overall, time to exhaustion and maximal running speed of the distance runners was improved during Ramadan fasting, independent of changes in nutrients intake observed during the current study. With proper modulation of training, distance runners performance can be maintained or even slightly improved following the month of Ramadan fasting.
Population Pharmacokinetics Modeling of Vancomycin Among Chinese Infants With Normal and Augmented Renal Function
Authors: Li De-Yi , Li Ling , Li Gui-Zhou , Hu Ya-Hui , Guo Hong-Li , Jing Xia , Chen Feng , Ji Xing , Xu Jing , Dai Hao-Ran
Published: September 2021

There have been good amounts of population pharmacokinetics (PPK) models of vancomycin for Chinese pediatric patients, but none of them had a special focus on modeling infant population with different levels of renal function. Since renal function variability is prominent among infant population and the clearance (CL) of vancomycin is heavily related to renal excretion, it is important to establish precise PPK models based on individual renal function levels. We employed a PPK approach to develop three models of vancomycin in parallel for Chinese pediatric patients with normal renal function [estimated glomerular filtration rate (eGFR) between 30 and 86 ml/min/1.73 m2, Model 1], with augmented renal function (eGFR ≥ 86 ml/min/1.73 m2, Model 2), or with all levels of renal function (Model 3). Three one-compartment models with first-order elimination kinetics were established. The predictive ability of Model 1 and Model 2 among each certain population is comparable with that of Model 3 with no statistical difference. Our study revealed that among the infant population with augmented renal function, only body weight was included as a covariate, which indicated that for an infant whose eGFR ≥ 86 ml/min/1.73 m2, taking blood sample is not compulsory for predicting vancomycin blood concentration, which avoids unnecessary injury to vulnerable infants.
Long-Term Effect of Non-Selective Beta-Blockers in Patients With Rheumatoid Arthritis After Myocardial Infarction—A Nationwide Cohort Study
Authors: Liu Sheng-Fu , Lee Chih-Kuo , Huang Kuan-Chih , Lin Lian-Yu , Hsieh Mu-Yang , Lin Ting-Tse
Published: September 2021

Objectives: Rheumatoid arthritis (RA) is an independent nontraditional risk factor for incidence of myocardial infarction (MI) and post-MI outcome is impaired in the RA population. Use of beta-blockers improves the long-term survival after MI in the general population while the protective effect of beta-blockers in RA patients is not clear. We investigate the impact of beta-blockers on the long-term outcome of MI among RA patients.

Methods: We identified RA subjects from the registries for catastrophic illness and myocardial infarction from 2003 to 2013. The enrolled subjects were divided into three groups according to the prescription of beta-blockers (non-user, non-selective, and β1-selective beta-blockers). The primary endpoint was all-cause mortality. We adjusted clinical variables and utilized propensity scores to balance confounding bias. Cox proportional hazards regression models were used to estimate the incidence of mortality in different groups.

Results: A total of 1,292 RA patients with myocardial infarction were enrolled, where 424 (32.8%), 281 (21.7%), and 587 (45.5%) subjects used non-user, non-selective, and β1-selective beta-blockers, respectively. Use of beta-blockers was associated with lower risk of all-cause mortality after adjustment with comorbidities, medications (adjusted hazard ratio [HR] 0.871; 95% confidence interval [CI] 0.727–0.978), and propensity score (HR 0.882; 95% CI 0.724–0.982). Compared with β1-selective beta-blockers, treatment with non-selective beta-blockers (HR 0.856; 95% CI 0.702–0.984) was significantly related to lower risk of mortality. The protective effect of non-selective beta-blockers remained in different subgroups including sex and different anti-inflammatory drugs.

Conclusion: Use of beta-blockers improved prognosis in post-MI patients with RA. Treatment with non-selective beta-blockers was significantly associated with reduced risk of mortality in RA patients after MI rather than β1-selective beta-blockers.
Organisational Climate and Pro-environmental Behaviours at Work: The Mediating Role of Personal Norms
Authors: Mouro Carla , Duarte Ana Patrícia
Published: September 2021

Organisations are currently strongly encouraged to adopt more responsible production patterns aligned with sustainable development goals (SDGs). Pro-environmental behaviours (PEBs) in the workplace can strengthen the expected positive impacts of organisations’ environmental performance and engender more sustainable transitions to low-carbon production. Research on PEBs at work is relatively recent, so this field still lacks studies of the role of organisational policies and practices in workers’ adoption of these behaviours and of psychosocial processes that contribute to more sustainable workplaces. The present research examined how perceptions of organisations’ environmental policies and practices (i.e., organisational climate or injunctive norms) and of coworkers’ PEBs (i.e., descriptive norms) affect employees’ self-reported voluntary PEBs. Thogersen’s norm taxonomy model was also applied to address the role of personal norms. Self-commitment to sustainable goals at work can play a fundamental role in workers’ behavioural choices, so this research further investigated whether personal norms mediate the relationship between perceived pro-environmental organisational climate and reported workplace PEBs. To test the proposed model, data were collected on 210 workers from different business sectors, who completed an online questionnaire. The analyses showed that, after controlling for the effects of tenure, education level, and a management position, a pro-environmental organisational climate predicts stronger personal norms and a greater tendency to adopt PEBs at work (adjusted R squared=0.36), providing evidence of complete mediation. Coworkers’ perceived descriptive norms also contribute directly to self-reported PEBs. The discussion of the results focuses on the importance of organisational level initiatives as a way to promote change in individuals’ behaviours, which can have positive consequences for workplaces’ transition to sustainability.
Tips for Effective Implementation of Virtual Reality Exposure Therapy in Phobias—A Systematic Review
Authors: Krzystanek Marek , Surma Stanisław , Stokrocka Małgorzata , Romańczyk Monika , Przybyło Jacek , Krzystanek Natalia , Borkowski Mariusz
Published: September 2021

Background: The high incidence of phobias and the limited accessibility of psychotherapy are the reasons for the search for alternative treatments that increase the availability of effective treatment. The use of virtual reality (VR) technology is an option with the potential to overcome the barriers in obtaining an effective treatment. VR exposure therapy (VRET) is based on a very similar rationale for in vivo exposure therapy. The study aimed to answer the question of how to perform exposure therapy in a virtual reality environment so that it is effective.

Methods: A systematic review of the literature, using PRISMA guidelines, was performed. After analysis of 362 records, 11 research papers on agoraphobia, 28 papers on social phobia and 10 about specific phobias were selected for this review.

Results: VRET in agoraphobia and social phobia is effective when performed from 8 to 12 sessions, on average once a week for at least 15 min. In turn, the treatment of specific phobias is effective even in the form of one longer session, lasting 45–180 min. Head mounted displays are an effective technology for VRET. Increasing the frequency of sessions and adding drug therapy may shorten the overall treatment duration. The effectiveness of VRET in phobias is greater without concomitant psychiatric comorbidity and on the condition of inducing and maintaining in the patient an experience of immersion in the VR environment. Long-term studies show a sustained effect of VRET in the treatment of phobias.

Conclusion: A large number of studies on in VR exposure therapy in phobias allows for the formulation of some recommendations on how to perform VRET, enabling the effective treatment. The review also indicates the directions of further VRET research in the treatment of phobias.
Trends of Antibiotic Use and Expenditure After an Intensified Antimicrobial Stewardship Policy at a 2,200-Bed Teaching Hospital in China
Authors: Qian Xiaodan , Pan Yuyan , Su Dan , Gong Jinhong , Xu Shan , Lin Ying , Li Xin
Published: September 2021

Objective: This study aimed to evaluate the effects of intensified Chinese special rectification activity on clinical antibiotic use (CSRA) policy on a tertiary-care teaching hospital.

Methods: A 48-month longitudinal dataset involving inpatients, outpatients, and emergency patients were collected. Study period included pre-intervention stage (adopting soft measures like systemic training) and post-intervention stage (applying antibiotic control system to intensify CSRA policy). Antibiotic use was evaluated by antibiotic use rate (AUR) or antibiotic use density (AUD). Economic indicator was evaluated by antibiotic cost in prescription or antibiotic expenditure in hospitalization. Data was analyzed by interrupted time series (ITS) analysis.

Results: The medical quality indicators remained stable or improved during the study period. AUR of inpatients (AURI) declined 0.553% per month (P = 0.025) before the intervention and declined 0.354% per month (P = 0.471) after the intensified CSRA policy was implemented. AUD, expressed as defined daily doses per 100 patients per day (DDDs/100PD), decreased by 1.102 DDDs/100PD per month (P = 0.021) before and decreased by 0.597 DDDs/100PD per month (P = 0.323) thereafter. The ratio of antibiotic expenditure to medication expenditure (AE/ME) decreased by 0.510% per month (P = 0.000) before and fell by 0.096% (P = 0.000) per month thereafter. AE per patient decreased by 25.309 yuan per month (P = 0.002) before and decreased by 7.987 yuan per month (P = 0.053) thereafter. AUR of outpatient (AURO) decreased by 0.065% per month before (P = 0.550) and decreased by 0.066% per month (P = 0.994) thereafter. The ratio of antibiotic cost to prescription cost in outpatient (ACO/PCO) decreased by 0.182% per month (P = 0.506) before and decreased by 0.216% per month (P = 0.906) thereafter. AUR of emergency patient (AURE) decreased by 0.400% per month (P = 0.044) before and decreased by 0.092% per month (P = 0.164) thereafter. The ratio of antibiotic cost to prescription cost in emergency patient (ACE/PCE) decreased by 0.616% per month (P < 0.001) before and decreased by 0.151% per month (P < 0.001) thereafter.

Conclusions: Implementation of CSRA policy was associated with declining antibiotic use and antibiotic expenditure in inpatients, outpatients, and emergency patients. However, it is also important to note that the declining trend of antibiotic consumption slowed due to the limited capacity for decline in the later stages of CSRA intervention.
Brain Tumour Temporal Monitoring of Interval Change Using Digital Image Subtraction Technique
Authors: Khalil Azira , Rahimi Aisyah , Luthfi Aida , Azizan Muhammad Mokhzaini , Satapathy Suresh Chandra , Hasikin Khairunnisa , Lai Khin Wee
Published: September 2021

A process that involves the registration of two brain Magnetic Resonance Imaging (MRI) acquisitions is proposed for the subtraction between previous and current images at two different follow-up (FU) time points. Brain tumours can be non-cancerous (benign) or cancerous (malignant). Treatment choices for these conditions rely on the type of brain tumour as well as its size and location. Brain cancer is a fast-spreading tumour that must be treated in time. MRI is commonly used in the detection of early signs of abnormality in the brain area because it provides clear details. Abnormalities include the presence of cysts, haematomas or tumour cells. A sequence of images can be used to detect the progression of such abnormalities. A previous study on conventional (CONV) visual reading reported low accuracy and speed in the early detection of abnormalities, specifically in brain images. It can affect the proper diagnosis and treatment of the patient. A digital subtraction technique that involves two images acquired at two interval time points and their subtraction for the detection of the progression of abnormalities in the brain image was proposed in this study. MRI datasets of five patients, including a series of brain images, were retrieved retrospectively in this study. All methods were carried out using the MATLAB programming platform. ROI volume and diameter for both regions were recorded to analyse progression details, location, shape variations and size alteration of tumours. This study promotes the use of digital subtraction techniques on brain MRIs to track any abnormality and achieve early diagnosis and accuracy whilst reducing reading time. Thus, improving the diagnostic information for physicians can enhance the treatment plan for patients.