bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-Term Effects of Gender-Affirming Hormone Therapy on Dysphoria and Quality of Life in Transgender Individuals: A Prospective Controlled Study
Authors: Foster Skewis Lucas , Bretherton Ingrid , Leemaqz Shalem Y. , Zajac Jeffrey D. , Cheung Ada S.
Published: July 2021

Background

Gender affirming hormone therapy (GAHT), whilst considered the standard of care in clinical guidelines for the treatment of many transgender (trans) people is supported by low quality evidence. In this prospective longitudinal controlled study, we aimed to examine the effect of newly commencing GAHT on gender dysphoria and quality of life (QoL) over a 6 month period.

Methods

Adult trans (including those with binary and/or non-binary identities) people newly commencing standard full-doses of masculinising (n = 42; 35 = trans masculine, 7 = non-binary) or feminising (n = 35; 33 = trans feminine, 2 = non-binary) GAHT and cisgender participants (n=53 male, n=50 female) were recruited to participate in this longitudinal prospective study. This analysis of gender dysphoria measured by the Gender Preoccupation and Stability Questionnaire and QoL measured by the RAND Short-Form 36 Health survey at baseline, 3 and 6 months after commencement of GAHT was a prespecified secondary outcome. Dysphoria and QoL over time in those starting GAHT compared to cisgender comparison group matched for their presumed sex at birth is reported as the mean difference (95% confidence interval) adjusted for age.

Results

In trans people initiating masculinising GAHT, there was a decrease in gender dysphoria with adjusted mean difference -6.80 (-8.68, -4.91), p < 0.001, and a clinically significant improvement in emotional well-being [adjusted mean difference 7.48 (1.32, 13.64), p = 0.018] and social functioning [adjusted mean difference 12.50 (2.84, 22.15), p = 0.011] aspects of QoL over the first 6 months of treatment relative to the cisgender female comparison group. No significant differences were observed in other QoL domains. In trans people initiating feminising GAHT, there was a decrease in gender dysphoria [adjusted mean difference -4.22 (-6.21, -2.24), p < 0.001] but no differences in any aspects of QoL were observed.

Conclusions

In the short-term, our findings support the benefit of initiating masculinising or feminising GAHT for gender dysphoria. Masculinising GAHT improves emotional well-being and social functioning within 6 months of treatment. Multidisciplinary input with speech pathology and surgery to support trans people seeking feminisation is likely needed. Further longitudinal studies controlled for other confounders (such as the presence of social supports) contributing to QoL are needed.
Social Vulnerability and Human Development of Brazilian Coastal Populations
Authors: Curi Rodrigo Luis Comini , Gasalla Maria A.
Published: July 2021

There is a considerable gap linking human dimensions and marine ecosystem services with Sustainable Development Goals, and one of these issues relate to differing perspectives and ideas around concepts of human development. There is also a lack of contemporary evaluations of coastal communities from developing nations under the lens of wellbeing and social vulnerability indexes. This study contributes to that discussion by presenting an analysis of Brazilian coastal municipalities, based on two indexes: The Social Vulnerability Index (SVI) and the Municipal Human Development Index (MHDI). These indicators intend to map some aspects of social well-being and development in the Brazilian territory under different perspectives. MHDI illustrates the average population conditions in a certain territory for humans to thrive, while the SVI points more specifically to the lack of assets necessary for wellbeing in a territory. The main aims are to map inequalities between coastal municipalities based on these two indexes and to provide a critical view reinforcing the importance of also considering natural capital as a key issue for wellbeing. Both indexes were developed with data from the Brazilian Institute of Geography and Statistics Census of 2010, the most recent one available for municipalities. Overall, 65.9 and 78% of a total of 387 Brazilian coastal municipalities assessed were ranked below SVI and MHDI country average values, respectively. Both indexes indicated higher human development conditions in Southern municipalities than in Northern ones, especially for income and education conditions, also showing large heterogeneity of discrepancies among and within regions. The importance of combined approaches for local socioeconomic wellbeing improvements, as measured by the MHDI and the SVI, and natural capital optimization seems essential for improvements in coastal communities’ quality-of-life conditions.
Sexual Dimorphism in Growth Rate and Gene Expression Throughout Immature Development in Wild Type Chrysomya rufifacies (Diptera: Calliphoridae) Macquart
Authors: Pimsler Meaghan L. , Hjelmen Carl E. , Jonika Michelle M. , Sharma Anika , Fu Shuhua , Bala Madhu , Sze Sing-Hoi , Tomberlin Jeffery K. , Tarone Aaron M.
Published: July 2021

Reliability of forensic entomology analyses to produce relevant information to a given case requires an understanding of the underlying arthropod population(s) of interest and the factors contributing to variability. Common traits for analyses are affected by a variety of genetic and environmental factors. One trait of interest in forensic investigations has been species-specific temperature-dependent growth rates. Recent work indicates sexual dimorphism may be important in the analysis of such traits and related genetic markers of age. However, studying sexual dimorphic patterns of gene expression throughout immature development in wild-type insects can be difficult due to a lack of genetic tools, and the limits of most sex-determination mechanisms. Chrysomya rufifacies, however, is a particularly tractable system to address these issues as it has a monogenic sex determination system, meaning females have only a single-sex of offspring throughout their life. Using modified breeding procedures (to ensure single-female egg clutches) and transcriptomics, we investigated sexual dimorphism in development rate and gene expression. Females develop slower than males (9 h difference from egg to eclosion respectively) even at 30°C, with an average egg-to-eclosion time of 225 h for males and 234 h for females. Given that many key genes rely on sex-specific splicing for the development and maintenance of sexually dimorphic traits, we used a transcriptomic approach to identify different expression of gene splice variants. We find that 98.4% of assembled nodes exhibited sex-specific, stage-specific, to sex-by-stage specific patterns of expression. However, the greatest signal in the expression data is differentiation by developmental stage, indicating that sexual dimorphism in gene expression during development may not be investigatively important and that markers of age may be relatively independent of sex. Subtle differences in these gene expression patterns can be detected as early as 4 h post-oviposition, and 12 of these nodes demonstrate homology with key Drosophila sex determination genes, providing clues regarding the distinct sex determination mechanism of C. rufifacies. Finally, we validated the transcriptome analyses through qPCR and have identified five genes that are developmentally informative within and between sexes.
Whole-Transcriptome Analysis of Preadipocyte and Adipocyte and Construction of Regulatory Networks to Investigate Lipid Metabolism in Sheep
Authors: Xiao Cheng , Wei Tian , Liu Li Xiang , Liu Jian Qiang , Wang Chun Xin , Yuan Zhi Yu , Ma Hui Hai , Jin Hai Guo , Zhang Li Chun , Cao Yang
Published: July 2021

Many local sheep breeds in China have poor meat quality. Increasing intramuscular fat (IMF) content can significantly improve the quality of mutton. However, the molecular mechanisms of intramuscular adipocyte formation and differentiation remain unclear. This study compared differences between preadipocytes and mature adipocytes by whole-transcriptome sequencing and constructed systematically regulatory networks according to the relationship predicted among the differentially expressed RNAs (DERs). Sequencing results showed that in this process, there were 1,196, 754, 100, and 17 differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), respectively. Gene Ontology analysis showed that most DERs enriched in Cell Part, Cellular Process, Biological Regulation, and Binding terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the DERs primarily focused on Focal adhesion, phosphoinositide 3-kinase (PI3K)-Akt, mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor (PPAR) signaling pathways. Forty (40) DERs were randomly selected from the core regulatory network to verify the accuracy of the sequence data. The results of qPCR showed that the DER expression trend was consistent with sequence data. Four novel promising candidate miRNAs (miR-336, miR-422, miR-578, and miR-722) played crucial roles in adipocyte differentiation, and they also participated in multiple and important regulatory networks. We verified the expression pattern of the miRNAs and related pathways’ members at five time points in the adipocyte differentiation process (0, 2, 4, 6, 8, 10 days) by qPCR, including miR-336/ACSL4/LncRNA-MSTRG71379/circRNA0002331, miR-422/FOXO4/LncRNA-MSTRG54995/circRNA0000520, miR-578/IGF1/LncRNA-MSTRG102235/circRNA0002971, and miR-722/PDK4/LncRNA-MSTRG107440/circ RNA0002909. In this study, our data provided plenty of valuable candidate DERs and regulatory networks for researching the molecular mechanisms of sheep adipocyte differentiation and will assist studies in improving the IMF.
Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components
Authors: Martins Susana G. , Zilhão Rita , Thorsteinsdóttir Sólveig , Carlos Ana Rita
Published: July 2021

Cells are subjected to endogenous [e.g., reactive oxygen species (ROS), replication stress] and exogenous insults (e.g., UV light, ionizing radiation, and certain chemicals), which can affect the synthesis and/or stability of different macromolecules required for cell and tissue function. Oxidative stress, caused by excess ROS, and DNA damage, triggered in response to different sources, are countered and resolved by specific mechanisms, allowing the normal physiological equilibrium of cells and tissues to be restored. One process that is affected by oxidative stress and DNA damage is extracellular matrix (ECM) remodeling, which is a continuous and highly controlled mechanism that allows tissues to readjust in reaction to different challenges. The crosstalk between oxidative stress/DNA damage and ECM remodeling is not unidirectional. Quite on the contrary, mutations in ECM genes have a strong impact on tissue homeostasis and are characterized by increased oxidative stress and potentially also accumulation of DNA damage. In this review, we will discuss how oxidative stress and DNA damage affect the expression and deposition of ECM molecules and conversely how mutations in genes encoding ECM components trigger accumulation of oxidative stress and DNA damage. Both situations hamper the reestablishment of cell and tissue homeostasis, with negative impacts on tissue and organ function, which can be a driver for severe pathological conditions.
Plasticity of the Immune System in Children Following Treatment Interruption in HIV-1 Infection
Authors: Sandgaard Katrine Schou , Margetts Ben , Attenborough Teresa , Gkouleli Triantafylia , Adams Stuart , Holm Mette , Gibb Diana , Gibbons Deena , Giaquinto Carlo , De Rossi Anita , Bamford Alasdair , Palma Paolo , Chain Benny , Gkazi Athina S. , Klein Nigel
Published: July 2021

It is intriguing that, unlike adults with HIV-1, children with HIV-1 reach a greater CD4+ T cell recovery following planned treatment cessation. The reasons for the better outcomes in children remain unknown but may be related to increased thymic output and diversity of T cell receptor repertoires. HIV-1 infected children from the PENTA 11 trial tolerated planned treatment interruption without adverse long-term clinical, virological, or immunological consequences, once antiretroviral therapy was re-introduced. This contrasts to treatment interruption trials of HIV-1 infected adults, who had rapid changes in T cells and slow recovery when antiretroviral therapy was restarted. How children can develop such effective immune responses to planned treatment interruption may be critical for future studies. PENTA 11 was a randomized, phase II trial of planned treatment interruptions in HIV-1-infected children (ISRCTN 36694210). In this sub-study, eight patients in long-term follow-up were chosen with CD4+ count>500/ml, viral load <50c/ml at baseline: four patients on treatment interruption and four on continuous treatment. Together with measurements of thymic output, we used high-throughput next generation sequencing and bioinformatics to systematically organize memory CD8+ and naïve CD4+ T cell receptors according to diversity, clonal expansions, sequence sharing, antigen specificity, and T cell receptor similarities following treatment interruption compared to continuous treatment. We observed an increase in thymic output following treatment interruption compared to continuous treatment. This was accompanied by an increase in T cell receptor clonal expansions, increased T cell receptor sharing, and higher sequence similarities between patients, suggesting a more focused T cell receptor repertoire. The low numbers of patients included is a limitation and the data should be interpreted with caution. Nonetheless, the high levels of thymic output and the high diversity of the T cell receptor repertoire in children may be sufficient to reconstitute the T cell immune repertoire and reverse the impact of interruption of antiretroviral therapy. Importantly, the effective T cell receptor repertoires following treatment interruption may inform novel therapeutic strategies in children infected with HIV-1.
Lactate-Dependent Regulation of Immune Responses by Dendritic Cells and Macrophages
Authors: Manoharan Indumathi , Prasad Puttur D. , Thangaraju Muthusamy , Manicassamy Santhakumar
Published: July 2021

For decades, lactate has been considered an innocuous bystander metabolite of cellular metabolism. However, emerging studies show that lactate acts as a complex immunomodulatory molecule that controls innate and adaptive immune cells’ effector functions. Thus, recent advances point to lactate as an essential and novel signaling molecule that shapes innate and adaptive immune responses in the intestine and systemic sites. Here, we review these recent advances in the context of the pleiotropic effects of lactate in regulating diverse functions of immune cells in the tissue microenvironment and under pathological conditions.
Immune Profile of the Normal Maternal-Fetal Interface in Rhesus Macaques and Its Alteration Following Zika Virus Infection
Authors: Moström Matilda J. , Scheef Elizabeth A. , Sprehe Lesli M. , Szeltner Dawn , Tran Dollnovan , Hennebold Jon D. , Roberts Victoria H. J. , Maness Nicholas J. , Fahlberg Marissa , Kaur Amitinder
Published: July 2021

The maternal decidua is an immunologically complex environment that balances maintenance of immune tolerance to fetal paternal antigens with protection of the fetus against vertical transmission of maternal pathogens. To better understand host immune determinants of congenital infection at the maternal-fetal tissue interface, we performed a comparative analysis of innate and adaptive immune cell subsets in the peripheral blood and decidua of healthy rhesus macaque pregnancies across all trimesters of gestation and determined changes after Zika virus (ZIKV) infection. Using one 28-color and one 18-color polychromatic flow cytometry panel we simultaneously analyzed the frequency, phenotype, activation status and trafficking properties of αβ T, γδ T, iNKT, regulatory T (Treg), NK cells, B lymphocytes, monocytes, macrophages, and dendritic cells (DC). Decidual leukocytes showed a striking enrichment of activated effector memory and tissue-resident memory CD4+ and CD8+ T lymphocytes, CD4+ Tregs, CD56+ NK cells, CD14+CD16+ monocytes, CD206+ tissue-resident macrophages, and a paucity of B lymphocytes when compared to peripheral blood. t-distributed stochastic neighbor embedding (tSNE) revealed unique populations of decidual NK, T, DC and monocyte/macrophage subsets. Principal component analysis showed distinct spatial localization of decidual and circulating leukocytes contributed by NK and CD8+ T lymphocytes, and separation of decidua based on gestational age contributed by memory CD4+ and CD8+ T lymphocytes. Decidua from 10 ZIKV-infected dams obtained 16-56 days post infection at third (n=9) or second (n=1) trimester showed a significant reduction in frequency of activated, CXCR3+, and/or Granzyme B+ memory CD4+ and CD8+ T lymphocytes and γδ T compared to normal decidua. These data suggest that ZIKV induces local immunosuppression with reduced immune recruitment and impaired cytotoxicity. Our study adds to the immune characterization of the maternal-fetal interface in a translational nonhuman primate model of congenital infection and provides novel insight in to putative mechanisms of vertical transmission.
Regulation of Inflammatory Cytokine Storms by Mesenchymal Stem Cells
Authors: Wang Lu , Li Yun , Xu Moyan , Deng Zihui , Zhao Yan , Yang Mengmeng , Liu Yuyan , Yuan Rui , Sun Yan , Zhang Hao , Wang Heming , Qian Zhirong , Kang Hongjun
Published: July 2021

Mesenchymal stem cells (MSCs) have been widely used in preclinical and clinical trials for various diseases and have shown great potential in the treatment of sepsis and coronavirus disease (COVID-19). Inflammatory factors play vital roles in the pathogenesis of diseases. The interaction between inflammatory factors is extremely complex. Once the dynamics of inflammatory factors are unbalanced, inflammatory responses and cytokine storm syndrome develop, leading to disease exacerbation and even death. Stem cells have become ideal candidates for the treatment of such diseases due to their immunosuppressive and anti-inflammatory properties. However, the mechanisms by which stem cells affect inflammation and immune regulation are still unclear. This article discusses the therapeutic mechanism and potential value of MSCs in the treatment of sepsis and the novel COVID-19, outlines how MSCs mediate innate and acquired immunity at both the cellular and molecular levels, and described the anti-inflammatory mechanisms and related molecular pathways. Finally, we review the safety and efficacy of stem cell therapy in these two diseases at the preclinical and clinical levels.
A Standardized Workflow Based on the STAVIRO Unbaited Underwater Video System for Monitoring Fish and Habitat Essential Biodiversity Variables in Coastal Areas
Authors: Pelletier Dominique , Roos David , Bouchoucha Marc , Schohn Thomas , Roman William , Gonson Charles , Bockel Thomas , Carpentier Liliane , Preuss Bastien , Powell Abigail , Garcia Jessica , Gaboriau Matthias , Cadé Florent , Royaux Coline , Le Bras Yvan , Reecht Yves
Published: July 2021

Essential Biodiversity Variables (EBV) related to benthic habitats and high trophic levels such as fish communities must be measured at fine scale but monitored and assessed at spatial scales that are relevant for policy and management actions. Local scales are important for assessing anthropogenic impacts, and conservation-related and fisheries management actions, while reporting on the conservation status of biodiversity to formulate national and international policies requires much broader scales. Measurements must account for the fact that coastal habitats and fish communities are heterogeneously distributed locally and at larger scales. Assessments based on in situ monitoring generally suffer from poor spatial replication and limited geographical coverage, which is challenging for area-wide assessments. Requirements for appropriate monitoring comprise cost-efficient and standardized observation protocols and data formats, spatially scalable and versatile data workflows, data that comply with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles, while minimizing the environmental impact of measurements. This paper describes a standardized workflow based on remote underwater video that aims to assess fishes (at species and community levels) and habitat-related EBVs in coastal areas. This panoramic unbaited video technique was developed in 2007 to survey both fishes and benthic habitats in a cost-efficient manner, and with minimal effect on biodiversity. It can be deployed in areas where low underwater visibility is not a permanent or major limitation. The technique was consolidated and standardized and has been successfully used in varied settings over the last 12 years. We operationalized the EBV workflow by documenting the field protocol, survey design, image post-processing, EBV production and data curation. Applications of the workflow are illustrated here based on some 4,500 observations (fishes and benthic habitats) in the Pacific, Indian and Atlantic Oceans, and Mediterranean Sea. The STAVIRO’s proven track-record of utility and cost-effectiveness indicates that it should be considered by other researchers for future applications.
Effects of Wave–Current Interaction on Storm Surge in the Pearl River Estuary: A Case Study of Super Typhoon Mangkhut
Authors: Luo Zhifa , Huang Bensheng , Chen Xiaohong , Tan Chao , Qiu Jing , Huang Guangling
Published: July 2021

This study explored the effects of interactions between waves and current on storm surge in the Pearl River Estuary (PRE) using a fully coupled wave–current model. The model was validated based on in situ observations during the traverse of super typhoon Mangkhut. The results indicated that the model could reproduce the storm surge and wave setup processes. Numerical experiments showed that simulations of storm surge are minimally affected by wave setup. The wave setup during super typhoon Mangkhut reached up to 0.23 m and contributed to the total near shore storm surge by up to 8%. The simulations of the coupled model showed a better correlation with observations compared to those of an uncoupled model. The storm surge increased with transport upstream in a tidal-dominated outlet, whereas it decreased in a river-dominated outlet. The storm surge and wave setup increased and decreased, respectively, during spring tide as compared to that during a neap tide. The storm surge increased with increasing runoff in the upper river reaches, whereas there was little change in the tidal-dominated lower river reaches. This research emphasizes the importance of integrating the effects of multiple dynamic factors in the forecasting of storm surge and provides a reference for similar studies in other estuaries with multiple outlets and a complex river network.
Challenging the Need for Deep Seabed Mining From the Perspective of Metal Demand, Biodiversity, Ecosystems Services, and Benefit Sharing
Authors: Miller K. A. , Brigden K. , Santillo D. , Currie D. , Johnston P. , Thompson K. F.
Published: July 2021

The extraction of minerals from the seabed of the deep oceans is of increasing interest to investors, mining companies and some coastal states. To date, no commercial-scale deep seabed mining has taken place but there is considerable pressure for minerals mining to become an economic reality, including to supply the projected demand for metals to support a global transition to renewable energy. At the same time, the full environmental impacts of deep seabed mining are difficult to predict but are expected to be highly damaging, both within, and perhaps well beyond, the areas mined. Here, we reflect on the considerable uncertainties that exist in relation to deep seabed mining. In particular, we provide a perspective on: (1) arguments that deep seabed mining is needed to supply minerals for the green energy revolution, using the electric vehicle battery industry as an illustration; (2) risks to biodiversity, ecosystem function and related ecosystem services; and (3) the lack of equitable benefit sharing to the global community now and for future generations. We explore the justification for a global moratorium on deep seabed mining to ensure protection of marine ecosystems, the need to focus on baseline research, and how improved governance of targeted marine regions could be key to the preservation and conservation of the ocean biome.
Ceramics From Ti-Extraction Blast Furnace Slag and Their Crystalline Phase, Microstructure, and Photocatalytic Performance
Authors: You Hao , Sun Hongjuan , Li Yao , Peng Tongjiang
Published: July 2021

To solve the environmental problems caused by the deposition of Ti-extraction blast furnace slag (EBFS) and to develop the functionality of the slag ceramics, photocatalytic EBFS ceramics were prepared via powder sintering at different temperatures. The phase composition dramatically changed in ceramics sintered at 1,000–1,150°C, but remained constant in samples treated at 1,150–1,200°C, just revealing the variations in the relative content of each phase. The photocatalytic performance of the samples was assessed through the catalytic degradation of Rhodamine B (RhB). Furthermore, it was shown to strongly depend on the relative Fe-bearing diopside content, achieving a maximum in EBFS-1180 ceramic. In this ceramic, the Fe-bearing diopside was found to degrade up to 77% of RhB under UV light irradiation at pH = 2, and its acid corrosion ratio after 24 h was only 0.03%, indicating that EBFS-1180 ceramic had the ability to degrade pollutants in an acidic environment.
Complement Component C3: A Novel Biomarker Participating in the Pathogenesis of Non-alcoholic Fatty Liver Disease
Authors: Han Juqiang , Zhang Xiang
Published: July 2021

Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disorder worldwide. The pathological spectrum of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) that induces progressive liver cirrhosis and eventually hepatocellular carcinoma (HCC). However, the molecular mechanisms driving the transformation of NASH are obscure. There is a compelling need for understanding the pathogenic mechanisms of NASH, and thereby providing new insight into mechanism-based therapy. Currently, several studies reported that complement system, an innate immune system, played an important role in the pathogenesis of NAFLD, which was also proved by our recent study. Complement component 3 (C3), a protein of the innate immune system, plays a hub role in the complement system. Herein, we present a review on the role and molecular mechanism of C3 in NASH as well as its implication in NASH diagnosis and treatment.
The Utility of PET/CT Metabolic Parameters Measured Based on Fixed Percentage Threshold of SUVmax and Adaptive Iterative Algorithm in the New Revised FIGO Staging System for Stage III Cervical Cancer
Authors: Zhang Yun , Hu Yuxiao , Zhao Shuang , Cui Can
Published: July 2021

Objectives: The main aim of this study was to evaluate the differences in metabolic parameters of positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) measured based on fixed percentage threshold of maximum standard uptake value (SUVmax) and adaptive iterative algorithm (AT-AIA) in patients with cervical cancer. Metabolic parameters in stage III patients subdivided into five groups according to FIGO and T staging (IIIB-T3B, IIIC1-T2B, IIIC1-T3B, IIIC2-T2B, IIIC2-T3B) were compared.

Methods: In total, 142 patients with squamous cell cervical cancer subjected to 18F-FDG-PET/CT before treatment were retrospectively reviewed. SUVmax, mean standard uptake value (SUVmean), maximum glucose homogenization (GNmax), mean glucose homogenization (GNmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and glucose homogenization total lesion glycolysis (GNTLG) values measured based on the above two measurement methods of all 142 patients (IIB-IVB) and 102 patients in the above five groups were compared.

Results: MTV measured based on fixed percentage threshold of SUVmax was lower than that based on AT-AIA (p < 0.05). MTV40%, MTV0.5, TLG0.5, GNTLG40%, and GNTLG0.5 values were significantly different among the five groups (p < 0.05) while the rest parameters were comparable (p > 0.05). All metabolic parameters of group IIIB-T3B were comparable to those of the other four groups. MTV40%, MTV0.5, GNTLG40%, and GNTLG0.5 in group IIIC1-T2B relative to IIIC1-T3B and those of group IIIC2-T2B relative to group IIIC2-T3B were significantly different. All metabolic parameters of group IIIC1-T2B relative to IIIC2-T2B and those of group IIIC1-T3B relative to group IIIC2-T3B were not significantly different.

Conclusion: Metabolic parameters obtained with the two measurement methods showed a number of differences. Selection of appropriate methods for measurement of 18F-FDG-PET/CT metabolic parameters is important to facilitate advances in laboratory research and clinical applications. When stage III patients had the same T stage, their metabolic parameters of local tumor were not significantly different, regardless of the presence or absence of lymph node metastasis, location of metastatic lymph nodes in the pelvic cavity or para-abdominal aorta. These results support the utility of the revised FIGO system for stage III cervical cancer, although our T-staging of stage III disease is incomplete.
Case Report: Ketogenic Diet Is Associated With Improvements in Chronic Obstructive Pulmonary Disease
Authors: Norwitz Nicholas G. , Winwood Russell , Stubbs Brianna J. , D'Agostino Dominic P. , Barnes Peter J.
Published: July 2021

Chronic Obstructive Pulmonary Disease (COPD) is a debilitating inflammatory respiratory condition that presents with worsening breathing difficulties and it is assumed to be progressive and incurable. As an inflammatory disease, COPD is associated with recruitment of immune cells to lung tissue and increased levels of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8, and GM-CSF. Low-carbohydrate ketogenic diets have anti-inflammatory properties that could, in theory, improve COPD symptoms and progression. Herein, we report on a 54-year-old patient (C.A.) with COPD who adopted a ketogenic diet (70% calories from fat). Subsequently, C.A. experienced a reduction in inflammatory markers in association with a meaningful improvement in lung function. His inflammatory markers decreased into the normal range and his forced expiratory volume increased by 37.5% relative to its pre-ketogenic diet value. Future research should explore nutritional ketosis and ketogenic diets as possible therapeutic options for individuals with COPD.
Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results
Authors: Kim Hyo Jin , Ryu Hyunjin , Kang Eunjeong , Kang Minjung , Han Miyeun , Song Sang Heon , Lee Joongyub , Jung Ji Yong , Lee Kyu-Beck , Sung Suah , Seong Eun Young , Ahn Curie , Oh Kook-Hwan
Published: July 2021

Background: We aimed to evaluate serum bicarbonate as a risk factor for renal progression, cardiovascular events, and mortality in Korean CKD patients.

Methods: We analyzed 1,808 participants from a Korean CKD cohort whose serum bicarbonate levels were measured at enrollment. Serum bicarbonate levels were categorized as low, lower normal, higher normal, and high (total carbon dioxide <22, 22–26, 26.1–29.9, and ≥30 mmol/L, respectively) groups. Metabolic acidosis was defined as a serum bicarbonate level <22 mmol/L. The primary outcome was renal events defined as doubling of serum creatinine, 50% reduction of eGFR from the baseline values, or development of end-stage kidney disease. The secondary outcome consisted of cardiovascular events and death. In addition, patients whose eGFR values were measured more than three times during the follow-up period were analyzed for eGFR decline. The rapid decline in eGFR was defined as lower than the median value of the eGFR slope.

Results: The mean serum bicarbonate level was 25.7 ± 3.7 mmol/L and 240 (13.2%) patients had metabolic acidosis. During the follow-up period of 55.2 ± 24.1 months, 545 (30.9%) patients developed renal events and 187 (10.6%) patients developed a composite of cardiovascular events and death. After adjustment, the low serum bicarbonate group experienced 1.27 times more renal events than the lower normal bicarbonate group [hazard ratio (HR): 1.27; 95% CI: 1.01–1.60, P = 0.043]. There was no significant association between the bicarbonate groups and the composite outcome of cardiovascular events and death. The low bicarbonate group showed a significantly rapid decline in eGFR [odds ratio (OR): 2.12; 95% CI: 1.39–3.22, P < 0.001] compared to the lower normal bicarbonate group.

Conclusions: Metabolic acidosis was significantly associated with increased renal events and a rapid decline in renal function in Korean predialysis CKD patients.
Motor Stereotypic Behavior Was Associated With Immune Response in Macaques: Insight From Transcriptome and Gut Microbiota Analysis
Authors: Pan Xuan , Liu Fangyuan , Song Yang , Wang Hongrun , Wang Lingyun , Qiu Hong , Price Megan , Li Jing
Published: July 2021

Motor stereotypic behaviors (MSBs) are common in captive rhesus macaques (Macaca mulatta) and human with psychiatric diseases. However, large gaps remain in our understanding of the molecular mechanisms that mediate this behavior and whether there are similarities between human and non-human primates that exhibit this behavior, especially at gene expression and gut microbiota levels. The present study combined behavior, blood transcriptome, and gut microbiota data of two groups of captive macaques to explore this issue (i.e., MSB macaques with high MSB exhibition and those with low: control macaques). Observation data showed that MSB macaques spent the most time on MSB (33.95%), while the CONTROL macaques allocated more time to active (30.99%) and general behavior (30.0%), and only 0.97% of their time for MSB. Blood transcriptome analysis revealed 382 differentially expressed genes between the two groups, with 339 upregulated genes significantly enriched in inflammation/immune response-related pathway. We also identified upregulated pro-inflammatory genesTNFRSF1A,IL1R1, andIL6R. Protein–protein interaction network analysis screened nine hub genes that were all related to innate immune response, and our transcriptomic results were highly similar to findings in human psychiatric disorders. We found that there were significant differences in the beta-diversity of gut microbiota between MSB and CONTROL macaques. Of whichPhascolarctobacterium, the producer of short chain fatty acids (SCFAs), was less abundant in MSB macaques. Meanwhile, PICRUSTs predicted that SCFAs intermediates biosynthesis and metabolic pathways were significantly downregulated in MSB macaques. Together, our study revealed that the behavioral, gene expression levels, and gut microbiota composition in MSB macaques was different to controls, and MSB was closely linked with inflammation and immune response. This work provides valuable information for future in-depth investigation of MSB and human psychiatric diseases.
Low Virulence of the Fungi Escovopsis and Escovopsioides to a Leaf-Cutting Ant-Fungus Symbiosis
Authors: Mendonça Débora Mello Furtado de , Caixeta Marcela Cristina Silva , Martins Gabriel Leite , Moreira Camila Costa , Kloss Thiago Gechel , Elliot Simon Luke
Published: July 2021

Eusocial insects interact with a diversity of parasites that can threaten their survival and reproduction. The amount of harm these parasites cause to their hosts (i.e., their virulence) can be influenced by numerous factors, such as the ecological context in which the parasite and its host are inserted. Leaf-cutting ants (genera Atta, Acromyrmex and Amoimyrmex, Attini: Formicidae) are an example of a eusocial insect whose colonies are constantly threatened by parasites. The fungi Escovopsis and Escovopsioides (Ascomycota: Hypocreales) are considered a highly virulent parasite and an antagonist, respectively, to the leaf-cutting ants’ fungal cultivar, Leucoagaricus gongylophorus (Basidiomycota: Agaricales). Since Escovopsis and Escovopsioides are common inhabitants of healthy colonies that can live for years, we expect them to have low levels of virulence. However, this virulence could vary depending on ecological context. We therefore tested two hypotheses: (i) Escovopsis and Escovopsioides are of low virulence to colonies; (ii) virulence increases as colony complexity decreases. For this, we used three levels of complexity: queenright colonies (fungus garden with queen and workers), queenless colonies (fungus garden and workers, without queen) and fungus gardens (without any ants). Each was inoculated with extremely high concentrations of conidia of Escovopsis moelleri, Escovopsioides nivea, the mycoparasitic fungus Trichoderma longibrachiatum or a blank control. We found that these fungi were of low virulence to queenright colonies. The survival of queenless colonies was decreased by E. moelleri and fungus gardens were suppressed by all treatments. Moreover, E. nivea and T. longibrachiatum seemed to be less aggressive than E. moelleri, observed both in vivo and in vitro. The results highlight the importance of each element (queen, workers and fungus garden) in the leaf-cutting ant-fungus symbiosis. Most importantly, we showed that Escovopsis may not be virulent to healthy colonies, despite commonly being described as such, with the reported virulence of Escovopsis being due to poor colony conditions in the field or in laboratory experiments.
Staphylococcus aureus α-Toxin Induces Acid Sphingomyelinase Release From a Human Endothelial Cell Line
Authors: Krones David , Rühling Marcel , Becker Katrin Anne , Kunz Tobias C. , Sehl Carolin , Paprotka Kerstin , Gulbins Erich , Fraunholz Martin
Published: July 2021

Staphylococcus aureus (S. aureus) is well known to express a plethora of toxins of which the pore-forming hemolysin A (α-toxin) is the best-studied cytolysin. Pore-forming toxins (PFT) permeabilize host membranes during infection thereby causing concentration-dependent effects in host cell membranes ranging from disordered ion fluxes to cytolysis. Host cells possess defense mechanisms against PFT attack, resulting in endocytosis of the breached membrane area and delivery of repair vesicles to the insulted plasma membrane as well as a concurrent release of membrane repair enzymes. Since PFTs from several pathogens have been shown to recruit membrane repair components, we here investigated whether staphylococcal α-toxin is able to induce these mechanisms in endothelial cells. We show that S. aureus α-toxin induced increase in cytosolic Ca2+ in endothelial cells, which was accompanied by p38 MAPK phosphorylation. Toxin challenge led to increased endocytosis of an extracellular fluid phase marker as well as increased externalization of LAMP1-positive membranes suggesting that peripheral lysosomes are recruited to the insulted plasma membrane. We further observed that thereby the lysosomal protein acid sphingomyelinase (ASM) was released into the cell culture medium. Thus, our results show that staphylococcal α-toxin triggers mechanisms in endothelial cells, which have been implicated in membrane repair after damage of other cell types by different toxins.
Rice Stripe Mosaic Disease: Characteristics and Control Strategies
Authors: Wang Zhiyi , Chen Biao , Zhang Tong , Zhou Guohui , Yang Xin
Published: July 2021

Rice stripe mosaic disease (RSMD) is caused by the rice stripe mosaic virus (RSMV; genus Cytorhabdovirus, family Rhabdoviridae). In recent years, significant progress has been made in understanding several aspects of the disease, especially its geographical distribution, symptoms, vectors, gene functions, and control measures. Since RSMD was first detected in southern China in 2015, it has been found in more and more rice growing areas and has become one of the most important rice diseases in southern China. RSMV is transmitted by the leafhopper Recilia dorsalis in a persistent-propagative manner, inducing yellow stripes, a slight distortion of leaves, increased tillers, and empty grains in rice plants. The virus has a negative-sense single-strand RNA genome of about 12.7 kb that encodes seven proteins: N, P, P3, M, G, P6, and L. Several molecular and serological tests have been developed to detect RSMV in plants and insects. The disease cycle can be described as follows: RSMV and its vector overwinter in infected plants; viruliferous R. dorsalis adults transmit the virus to spring rice and lay eggs on the infected seedlings; the next generation of R. dorsalis propagate on infected seedlings, become viruliferous, disperse, and cause new disease outbreaks. Control measures include monitoring and accurate forecasting, selecting disease-resistant varieties, improving cultivation systems, covering rice seedling nurseries with insect-proof nets, and using pesticides rationally. Inappropriate cultivation systems, pesticide overuse, and climatic conditions contribute to epidemics by affecting the development of vector insects and their population dynamics.
Mass Spectrometry Imaging for Glycome in the Brain
Authors: Hasan Md. Mahmudul , Mimi Mst. Afsana , Mamun Md. Al , Islam Ariful , Waliullah A. S. M. , Nabi Md. Mahamodun , Tamannaa Zinat , Kahyo Tomoaki , Setou Mitsutoshi
Published: July 2021

Glycans are diverse structured biomolecules that play crucial roles in various biological processes. Glycosylation, an enzymatic system through which various glycans are bound to proteins and lipids, is the most common and functionally crucial post-translational modification process. It is known to be associated with brain development, signal transduction, molecular trafficking, neurodegenerative disorders, psychopathologies, and brain cancers. Glycans in glycoproteins and glycolipids expressed in brain cells are involved in neuronal development, biological processes, and central nervous system maintenance. The composition and expression of glycans are known to change during those physiological processes. Therefore, imaging of glycans and the glycoconjugates in the brain regions has become a “hot” topic nowadays. Imaging techniques using lectins, antibodies, and chemical reporters are traditionally used for glycan detection. However, those techniques offer limited glycome detection. Mass spectrometry imaging (MSI) is an evolving field that combines mass spectrometry with histology allowing spatial and label-free visualization of molecules in the brain. In the last decades, several studies have employed MSI for glycome imaging in brain tissues. The current state of MSI uses on-tissue enzymatic digestion or chemical reaction to facilitate successful glycome imaging. Here, we reviewed the available literature that applied MSI techniques for glycome visualization and characterization in the brain. We also described the general methodologies for glycome MSI and discussed its potential use in the three-dimensional MSI in the brain.
Student Behavior Recognition From Heterogeneous View Perception in Class Based on 3-D Multiscale Residual Dense Network for the Analysis of Case Teaching
Authors: Liu Hui , Liu Yang , Zhang Ran , Wu Xia
Published: July 2021

The study of student behavior analysis in class plays a key role in teaching and educational reforms that can help the university to find an effective way to improve students' learning efficiency and innovation ability. It is also one of the effective ways to cultivate innovative talents. The traditional behavior recognition methods have many disadvantages, such as poor robustness and low efficiency. From a heterogeneous view perception point of view, it introduces the students' behavior recognition. Therefore, we propose a 3-D multiscale residual dense network from heterogeneous view perception for analysis of student behavior recognition in class. First, the proposed method adopts 3-D multiscale residual dense blocks as the basic module of the network, and the module extracts the hierarchical features of students' behavior through the densely connected convolutional layer. Second, the local dense feature of student behavior is to learn adaptively. Third, the residual connection module is used to improve the training efficiency. Finally, experimental results show that the proposed algorithm has good robustness and transfer learning ability compared with the state-of-the-art behavior recognition algorithms, and it can effectively handle multiple video behavior recognition tasks. The design of an intelligent human behavior recognition algorithm has great practical significance to analyze the learning and teaching of students in the class.
Epilepsy Personal Assistant Device—A Mobile Platform for Brain State, Dense Behavioral and Physiology Tracking and Controlling Adaptive Stimulation
Authors: Pal Attia Tal , Crepeau Daniel , Kremen Vaclav , Nasseri Mona , Guragain Hari , Steele Steven W. , Sladky Vladimir , Nejedly Petr , Mivalt Filip , Herron Jeffrey A. , Stead Matt , Denison Timothy , Worrell Gregory A. , Brinkmann Benjamin H.
Published: July 2021

Epilepsy is one of the most common neurological disorders, and it affects almost 1% of the population worldwide. Many people living with epilepsy continue to have seizures despite anti-epileptic medication therapy, surgical treatments, and neuromodulation therapy. The unpredictability of seizures is one of the most disabling aspects of epilepsy. Furthermore, epilepsy is associated with sleep, cognitive, and psychiatric comorbidities, which significantly impact the quality of life. Seizure predictions could potentially be used to adjust neuromodulation therapy to prevent the onset of a seizure and empower patients to avoid sensitive activities during high-risk periods. Long-term objective data is needed to provide a clearer view of brain electrical activity and an objective measure of the efficacy of therapeutic measures for optimal epilepsy care. While neuromodulation devices offer the potential for acquiring long-term data, available devices provide very little information regarding brain activity and therapy effectiveness. Also, seizure diaries kept by patients or caregivers are subjective and have been shown to be unreliable, in particular for patients with memory-impairing seizures. This paper describes the design, architecture, and development of the Mayo Epilepsy Personal Assistant Device (EPAD). The EPAD has bi-directional connectivity to the implanted investigational Medtronic Summit RC+STM device to implement intracranial EEG and physiological monitoring, processing, and control of the overall system and wearable devices streaming physiological time-series signals. In order to mitigate risk and comply with regulatory requirements, we developed a Quality Management System (QMS) to define the development process of the EPAD system, including Risk Analysis, Verification, Validation, and protocol mitigations. Extensive verification and validation testing were performed on thirteen canines and benchtop systems. The system is now under a first-in-human trial as part of the US FDA Investigational Device Exemption given in 2018 to study modulated responsive and predictive stimulation using the Mayo EPAD system and investigational Medtronic Summit RC+STM in ten patients with non-resectable dominant or bilateral mesial temporal lobe epilepsy. The EPAD system coupled with an implanted device capable of EEG telemetry represents a next-generation solution to optimizing neuromodulation therapy.