bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the efficacy of using indocyanine green associated with fluorescence in sentinel lymph node biopsy
Authors: da Silva Sá Rafael , Von Ah Rodrigues Raquel Fujinohara , Antônio Bugalho Luiz , da Silva Suelen Umbelino , Pinto Nazário Afonso Celso 
Published: September 2022

AbstractIntroduction: Sentinel lymph node biopsy is the established technique in the axillary staging of patients with early breast cancer without clinical axillary involvement. Three techniques are widely used globally for the detection of sentinel lymph nodes: patent blue; the radiopharmaceutical technetium 99 with the use of the gamma probe; and the combination of these two techniques. Objectives: To evaluate the sentinel lymph node detection rate with an innovative technique: indocyanine green associated with fluorescence in breast cancer patients, its comparison with the other methods (patent blue and combined patent blue + indocyanine green). Methods: Ninety-nine patients were subdivided into three arms with 33 patients, one arm was submitted to the sentinel lymph node technique using patent blue, the other indocyanine green, and the third a combination of the two dyes. Results: The accuracy rate in the identification of the sentinel lymph node was 78.8% with the use of patent blue, 93.9% with indocyanine green and 100% with patent blue + indocyanine green. The combined group identified mainly two sentinel nodes (48.5%); however, the other groups more commonly identified only one sentinel lymph node. The mean time of sentinel lymph node identification was 20.6 minutes among patients submitted to the traditional dye, 8.6 minutes in the indocyanine green arm and 10 minutes in the combination of the two methods (P<0.001). The mean surgery time was 69.4 minutes with patent blue, 55.1 minutes with indocyanine green and 69.4 minutes with the combination (P<0.001). Conclusions: The sentinel lymph node detection rate by fluorescence with the use of indocyanine green was considered effective. The comparison of the sentinel lymph node detection rate between the use of patent blue, indocyanine green and patent blue + indocyanine green (combined) revealed statistically significant differences (p=0.030), with the combined method being the most effective.
Medial prefrontal transcranial alternating current stimulation for apathy in Huntington’s disease
Authors: Davis Marie-Claire , Hill Aron T. , Fitzgerald Paul B. , Bailey Neil W. , Sullivan Caley , Stout Julie C. , Hoy Kate E. 
Published: September 2022

AbstractWe investigated the effects of transcranial alternating current stimulation (tACS) targeted to the bilateral medial prefrontal cortex (mPFC) and administered at either delta or alpha frequencies, on brain activity and apathy in people with Huntington’s disease (HD) (n = 17). Neurotypical controls (n = 20) were also recruited for comparison. All participants underwent three 20-minute sessions of tACS; one session at alpha frequency (Individualised Alpha Frequency (IAF), or 10Hz when an IAF was not detected); one session at delta frequency (2Hz); and a session of sham tACS. Participants completed the Monetary Incentive Delay (MID) task with simultaneous recording of EEG immediately before and after each tACS condition. The MID task presents participants with cues signalling potential monetary gains or losses that increase activity in key regions of the cortico-basal ganglia-thalamocortical networks, with dysfunction of the latter network being implicated in the pathophysiology of apathy. We used the P300 and Contingent Negative Variation (CNV) event-related potentials elicited during the MID task as markers of mPFC engagement. HD participants’ CNV amplitude significantly increased in response to alpha-tACS, but not delta-tACS or sham. Neurotypical controls’ P300 and CNV were not modulated by any of the tACS conditions, but they did demonstrate a significant decrease in post-target response times following alpha-tACS. We present this as preliminary evidence of the ability of alpha-tACS to modulate brain activity associated with apathy in HD.
Normal values for native T1 at 1.5T in the pericardial fluid of healthy volunteers
Authors: Thalén Simon , Ramos Joao G , Engblom Henrik , Sigfridsson Andreas , Sörensson Peder , Ugander Martin 
Published: September 2022

AbstractBackgroundT1 mapping cardiovascular magnetic resonance (CMR) imaging has been used to characterize pericardial effusions. The aim of this study was to measure pericardial fluid native T1 values in healthy volunteers to establish normal values.MethodsProspectively recruited volunteers (n=30) underwent CMR at 1.5T and native T1 maps were acquired using a MOLLI 5s(3s)3s acquisition scheme. A volume of pericardial fluid was imaged in a short-axis slice and in a slice perpendicular to the short-axis orientation. A reliable measurement had a region of interest size >10 mm2, coefficient of variation <10 %, and a relative difference <5 % between the two slice orientations.ResultsIn 26/30 (87%) of volunteers, there was a sufficient amount of pericardial fluid to enable reliable measurement. Native T1 of pericardial fluid was 3262±163 (95% normal limits 2943–3581ms), and did not differ in the perpendicular slice orientation (3267±173 ms, p=0.75), due to sex (female 3311±177 vs. male 3220±142 ms, p=0.17), or age (R2=0.07, p=0.2)ConclusionsThis study shows that T1 values can be reliably measured in the pericardial fluid of healthy volunteers. It is the first to report normal reference ranges for T1 values at 1.5T in the pericardial fluid of healthy volunteers.
Agricultural land use and lake morphology explain substantial variation in water quality across Canada
Authors: Schacht Joe R. Sánchez , MacKeigan Paul W. , Taranu Zofia E. , Huot Yannick , Gregory-Eaves Irene 
Published: September 2022

AbstractDespite decades of research and mitigation efforts, declines in freshwater quality resulting from anthropogenic nutrient input remain a persistent issue worldwide. Canada has the greatest number of freshwater lakes in the world, yet we have a limited understanding of the magnitude and scale at which most lakes have been affected by human activities, namely Land Use/Land Cover (LULC) alterations. In response, the NSERC Canadian Lake Pulse Network has compiled the first nationwide systematic database of lake quality metrics by surveying 664 lakes across 12 ecozones over three years. To assess the influence of catchment development on water quality and its spatial variation, we built models quantifying the association between watershed LULC and water quality. We found that agricultural and urban land use explained the greatest proportion of variation in water quality among LULC categories (R2= 0.20–0.29). Overall, our study highlights that drivers of water quality are similar across regions; however, baseline conditions vary, so freshwater ecosystem management strategies must consider their geographic context to better predict where water quality thresholds will be surpassed.
PNuts: Global spatio-temporal database of plant nutritional properties
Authors: Berzaghi Fabio , Bretagnolle Francois , Ratshikombo Zwanga , Abdallah Alya Ben 
Published: September 2022

AbstractPlant nutritional properties (crude protein, fibers, minerals, and carbohydrates) and chemical defenses (tannins and phenols) are key traits determining food quality and feeding preferences of animals and humans. Plant nutritional properties are also relevant to crop production and livestock. Here we present PNuts, a global database containing > 1000 species and > 13,000 records of nutritional properties of different plant organs complete with location and time of collection (year/month/season). Species include crops and wild plants and are classified in six functional groups: legumes, herbs, grasses, lianas, shrubs and trees. Plant organs include leaf, fruit, seed, stem, twigs, flower, root, and bark. PNuts data can be used as inputs for ecological analyses and model parametrization requiring large amounts of data. PNuts provides an important tool to better understand the importance of nutritional properties in plant eco-physiology and the implications for humans and animals’ food quality and plant-animal interactions in a context of global changes.
Environmentally robustcis-regulatory changes underlie rapid climatic adaptation
Authors: Ballinger Mallory A. , Mack Katya L. , Durkin Sylvia M. , Riddell Eric A. , Nachman Michael W. 
Published: September 2022

Changes in gene expression are proposed to play a major role in adaptive evolution. While it is known that gene expression is highly sensitive to the environment, very few studies have determined the influence of genetic and environmental effects on adaptive gene regulation in natural populations. Here, we utilize allele-specific expression to characterizecisandtransgene regulatory divergence in temperate and tropical house mice in two metabolic tissues under two thermal conditions. First, we show that gene expression divergence is pervasive between populations and across thermal conditions, with roughly 5-10% of genes exhibiting genotype-by-environment interactions. Second, we found that most expression divergence was due tocis-regulatory changes that were stable across temperatures. In contrast, patterns of expression plasticity were largely attributable totrans-effects, which showed greater sensitivity to temperature. Nonetheless, we discovered a small subset of temperature-dependentcis-regulatory changes, thereby identifying loci underlying expression plasticity. Finally, we performed scans for selection in wild house mice to identify genomic signatures of rapid adaptation. Genomic outliers were enriched in genes with evidence forcis-regulatory divergence. Notably, these genes were associated with phenotypes that affected body weight and metabolism, suggesting thatcis-regulatory changes are a possible mechanism for adaptive body size evolution between populations. Our results show that gene expression plasticity, largely controlled intrans, may facilitate the colonization of new environments, but that evolved changes in gene expression are largely controlled incis, illustrating the genetic and non-genetic mechanisms underlying the establishment of populations in new environments.Significance StatementGene expression variation is shaped by both genetic and environmental effects, yet these two factors are rarely considered together in the context of adaptive evolution. We studied environmental influences on gene regulatory evolution in temperate and tropical house mice in cold and warm laboratory environments. We discovered that genetic effects in the form ofcis-regulatory divergence were pervasive and largely insensitive to the environment. Many of these genetic effects are under selection and are associated with genes that affect body size, suggestingcis-regulatory changes as a possible mechanism for adaptive body size evolution. We also discovered manytrans-effects controlling expression plasticity, demonstrating the importance of both genetic and non-genetic changes associated with adaptation over short timescales (a few hundred generations).
Chromosomal and gonadal sex drive sex differences in lipids and hepatic gene expression in response to hypercholesterolemia and statin treatment
Authors: Wiese Carrie B. , Agle Zoey W. , Zhang Peixiang , Reue Karen 
Published: September 2022

ABSTRACTBackgroundBiological sex impacts susceptibility and presentation of cardiovascular disease, which remains the leading cause of death for both sexes. To reduce cardiovascular disease risk, statin drugs are commonly prescribed to reduce circulating cholesterol levels through inhibition of cholesterol synthesis. The effectiveness of statin therapy differs between individuals with a sex bias in the frequency of adverse effects. Limited information is available regarding the mechanisms driving sex-specific responses to hypercholesterolemia or statin treatment.MethodsFour core genotypes mice (XX and XY mice with ovaries and XX and XY mice with testes) on a hypercholesteremic Apoe−/− background were fed a chow diet without or with simvastatin for 8 weeks. Plasma lipid levels were quantified and hepatic differential gene expression was evaluated with RNA-sequencing to identify the independent effects of gonadal and chromosomal sex.ResultsIn a hypercholesterolemic state, gonadal sex influenced the expression levels of more than 3000 genes, and chromosomal sex impacted expression of nearly 1400 genes, which were distributed across all autosomes as well as the sex chromosomes. Gonadal sex uniquely influenced the expression of ER stress response genes, whereas chromosomal and gonadal sex influenced fatty acid metabolism gene expression in hypercholesterolemic mice. Sex-specific effects on gene regulation in response to statin treatment included a compensatory upregulation of cholesterol biosynthetic gene expression on mice with XY chromosome complement, regardless of presence of ovaries or testes.ConclusionGonadal and chromosomal sex have independent effects on the hepatic transcriptome to influence different cellular pathways in a hypercholesterolemic environment. Furthermore, chromosomal sex in particular impacted the cellular response to statin treatment. An improved understanding of how gonadal and chromosomal sex influence cellular response to disease conditions and in response to drug treatment is critical to optimize disease management for all individuals.
HUMAN FECAL BILE ACID ANALYSIS AFTER INVESTIGATIONAL MICROBIOTA-BASED LIVE BIOTHERAPEUTIC DELIVERY FOR RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION
Authors: Papazyan Romeo , Ferdyan Nicky , Srinivasan Karthik , Gonzalez Carlos , Shannon Bill , Blount Ken , Fuchs Bryan C. 
Published: September 2022

ABSTRACTIntestinal microbiome disruption is associated with recurrent Clostridioides difficile infection (rCDI), which poses a high risk of morbidity and mortality. Microbiome-based therapeutics are increasingly evaluated as a strategy to reduce rCDI, and their proposed mechanisms include restoration of the microbiota and microbiota-mediated functions, including bile acid (BA) metabolism. This study reports the development of a highly quantitative and sensitive assay for targeted metabolomic assessment of bile acids, and the application of the assay to profile bile acid composition in a Phase 2 trial of the investigational microbiota-based live biotherapeutic RBX2660 for reduction of rCDI (PUNCH CD2; NCT02299570). Participants were asked to provide stool samples before and up to 24 months after treatment. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 35 BAs from a total of 113 participant stool samples from 27 rCDI participants treated with RBX2660 in the double-blinded, placebo-controlled clinical trial. The results demonstrate a high-confidence assay as represented by sensitivity, linearity, accuracy, and precision of the output measurements of BAs. When the assay was utilized to assess stool samples from the clinical trial participants, primary BAs were the dominant BA species at baseline, consistent with the expected loss of commensals after broad-spectrum antibiotic treatment. As early as 7 days after RBX2660 administration, there was a significant drop in primary BAs concurrent with increased secondary BAs, and this profile was sustained through 24 months after RBX2660 administration. Taken together, we describe a robust assay that demonstrates altered BA metabolism associated with RBX2660 administration, shifting towards a profile that is consistent with a healthier BA profile and clinical response.
The effect of variation of individual infectiousness on SARS-CoV-2 transmission in households
Authors: Tsang Tim K. , Huang Xiaotong , Wang Can , Chen Sijie , Yang Bingyi , Cauchemez Simon , Cowling Benjamin J. 
Published: September 2022

AbstractQuantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases (including SARS-CoV-2). However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2-4.2 fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management.One Sentence SummaryIn this study, variation of individual infectiousness is quantified. Potential sources of such variation, particularly heterogeneity of viral shedding is discussed.
Antibody and memory B cell responses to the dengue virus NS1 antigen in individuals with varying severity of past infection
Authors: Ramu Shyrar Tanussiya , Dissanayake Madushika , Jeewandara Chandima , Bary Farha , Harvie Michael , Gomes Laksiri , Wijesinghe Ayesha , Ogg Graham S. , Malavige Gathsaurie Neelika 
Published: September 2022

AbstractBackgroundTo further understand the role of NS1 specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody sub-class profiles and NS1 specific memory B cell responses (Bmems) in individuals, with varying severity of past dengue.MethodsNabs (Neut50 titres) were assessed using Foci Reduction Neutralization Test (FRNT) and in-house ELISAs were used to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n=22), those with past DHF (n=14) and seronegative (SN) individuals (n=7). B cell ELISpot assays were used to assess NS1-specific Bmem responses.Results15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p=0.0006) and DENV4 (p= 0.0127), in those with past DHF, whereas there was no significant difference in titres was seen for different DENV serotypes in those with past DF. Overall NS1-Ab to all serotypes and NS1-specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1-specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 corelated with DENV1 specific NS1-Abs levels (Spearman r=0.35, p=0.02), there was no correlation with other DENV serotypes.ConclusionsWe found that those with past DF had broadly cross reactive Nabs, while those with past DHF had higher NS1-Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1-specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease.
Longitudinal IgG antibody responses to Plasmodium vivax blood-stage antigens during and after acute vivax malaria in individuals living in the Brazilian Amazon
Authors: Tashi Tenzin , Upadhye Aditi , Kundu Prasun , Wu Chunxiang , Menant Sébastien , Soares Roberta Reis , Ferreira Marcelo Urbano , Longley Rhea J. , Mueller Ivo , Hoang Quyen Q. , Tham Wai-Hong , Rayner Julian C. , KG Scopel Kézia , Lima Junior Josué C. , Tran Tuan M. 
Published: September 2022

ABSTRACTBackgroundTo make progress towards malaria elimination, a highly effective vaccine targeting Plasmodium vivax is urgently needed. Evaluating the kinetics of natural antibody responses to vaccine candidate antigens after acute vivax malaria can inform the design of serological markers of exposure and vaccines.Methodology/Principal FindingsThe responses of IgG antibodies to 9 P. vivax vaccine candidate antigens were evaluated in longitudinal serum samples from Brazilian individuals collected at the time of acute vivax malaria and 30, 60, and 180 days afterwards. Antigen-specific IgG correlations, seroprevalence, and half-lives were determined for each antigen using the longitudinal data. Antibody reactivity against Pv41 and PVX_081550 strongly correlated within each of the four time points. The analysis identified robust responses in terms of magnitude and seroprevalence against Pv41 and PvGAMA at 30 and 60 days. Among the 8 P. vivax antigens demonstrating >50% seropositivity across all individuals, antibodies specific to PVX_081550 had the longest half-life 100 days (95% CI, 83—130 days), followed by PvRBP2b (91 days; 95% CI, 76—110 days) and Pv12 (82 days; 95% CI, 64—110 days).Conclusion/SignificanceThis study provides an in-depth assessment of the kinetics of antibody responses to key vaccine candidate antigens in Brazilians with acute vivax malaria. Follow-up studies are needed to determine whether the longer-lived antibody responses induced by natural infection are effective in controlling blood-stage infection and mediating clinical protection.AUTHOR SUMMARYTo successfully eliminate malaria, highly effective vaccines against the two major human malaria species, Plasmodium falciparum and Plasmodium vivax, will be needed. Vaccines against the blood form of malaria generate antibodies that target specific proteins on the Plasmodium parasite to reduce its replication within the host. Studying the antibody response after natural malaria infection can help identify blood markers of parasite exposure and also shed light on the magnitude and longevity of antibodies to vaccine candidate proteins. We performed a study to determine the frequency, magnitude, and longevity of natural antibody responses against nine P. vivax vaccine candidate proteins in patients with vivax malaria in Brazil. These proteins were selected based on prior studies demonstrating that antibodies against these proteins were either associated with protection against vivax malaria or have been tested as blood markers of recent infection with vivax malaria. We identify specific vivax proteins that produce more frequent and longer-lived antibody responses in this population.