bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA-Seq Analysis of the Growth Hormone Transgenic Female Triploid Atlantic Salmon (Salmo salar) Hepatic Transcriptome Reveals Broad Temperature-Mediated Effects on Metabolism and Other Biological Processes
Authors: Ignatz Eric H. , Hori Tiago S. , Kumar Surendra , Benfey Tillmann J. , Braden Laura M. , Runighan C. Dawn , Westcott Jillian D. , Rise Matthew L. 
Published: May 2022

This study examined the impact of rearing temperature (10.5, 13.5 or 16.5°C) on the hepatic transcriptome of AquAdvantage Salmon (growth hormone transgenic female triploid Atlantic salmon) at an average weight of 800 g. Six stranded PE libraries were Illumina-sequenced from each temperature group, resulting in an average of over 100 M raw reads per individual fish. RNA-sequencing (RNA-seq) results showed the greatest difference in the number of differentially expressed transcripts (1750 DETs), as revealed by both DESeq2 and edgeR (q &lt; 0.05; fold-change &gt; |1.5|), was between the 10.5 and 16.5°C temperature groups. In contrast, 172 and 52 DETs were found in the 10.5 vs. 13.5°C and the 13.5 vs. 16.5°C comparisons, respectively. Considering the DETs between the 10.5 and 16.5°C groups, 282 enriched gene ontology (GO) terms were identified (q &lt; 0.05), including “response to stress”, “immune system process”, “lipid metabolic process”, “oxidation-reduction process”, and “cholesterol metabolic process”, suggesting elevated temperature elicited broad effects on multiple biological systems. Pathway analysis using ClueGO showed additional impacts on amino acid and lipid metabolism. There was a significant positive correlation between RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) results for 8 of 9 metabolic-related transcripts tested. RT-qPCR results also correlated to changes in fillet tissue composition previously reported in these salmon (e.g., methionine and lysine concentrations positively correlated with hsp90ab1 transcript expression), suggesting that rearing temperature played a significant role in mediating metabolic/biosynthetic pathways of AquAdvantage Salmon. Many transcripts related to lipid/fatty acid metabolism (e.g., elovl2, fabpi, hacd2, mgll, s27a2, thrsp) were downregulated at 16.5°C compared to both other temperature groups. Additionally, enrichment of stress-, apoptosis- and catabolism-relevant GO terms at 16.5°C suggests that this temperature may not be ideal for commercial production when using freshwater recirculating aquaculture systems (RAS). This study relates phenotypic responses to transcript-specific findings and therefore aids in the determination of an optimal rearing temperature for AquAdvantage Salmon. With approval to grow and sell AquAdvantage Salmon in the United States and Canada, the novel insights provided by this research can help industry expansion by promoting optimal physiological performance and health.
Proteomic Profiling of Cryoglobulinemia
Authors: Liu Peng , Wu Jianqiang , Sun Dandan , Li Haolong , Qi Zhihong , Tang Xiaoyue , Su Wei , Li Yongzhe , Qin Xuzhen 
Published: May 2022

ObjectiveWe aimed to explore and identify candidate protein biomarkers of cryoglobulinemia (CGE) in disease control patients with negative cryoglobulin (DC) or healthy controls (HCs).MethodsThe tandem mass tag (TMT)-labeled serum quantitative proteomics approach was used to identify differentially expressed proteins between the CGE and DC groups. Ingenuity pathway analysis was used for functional annotation of differentially expressed proteins. Biomarker candidates were validated in another cohort using the parallel reaction monitoring (PRM) method. Apolipoprotein A1 (APOA1), apolipoprotein CIII (APOC3), adiponectin, and proprotein convertase subtilisin/kexin type-9 (PCSK9), which represent key proteins involved in the cholesterol metabolism pathway, were further verified in an increased number of samples by enzyme-linked immunosorbent assay (ELISA).ResultsA total of 1004 proteins were identified, of which 109 proteins were differentially expressed between the CGE and DC groups. These differentially expressed proteins were primarily involved in hepatic fibrosis/hepatic stellate cell activation and immune/inflammation-related pathways. In the disease and biofunction analysis, these proteins were mainly associated with the adhesion of blood cells, leukocyte migration, cholesterol transport, and transport of lipids. Twelve candidate biomarkers were validated by PRM-based proteomics, and proteins involved in the cholesterol metabolism pathway were further verified. APOA1, APOC3, adiponectin and PCSK9 concentrations were increased in CGE patients compared with healthy controls (P=0.0123, 0.1136, 0.5760, and 0.0019, respectively).ConclusionThis report describes the first application of a TMT-PRM-ELISA workflow to identify and validate CGE-specific biomarkers in serum. APOA1 and PCSK9 have been confirmed to be increased in CGE patients, demonstrating that proteins involved in cholesterol metabolism are also implicated in the development of CGE. These findings contribute to pathogenesis research and biomarker discovery in CGE.
Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries
Authors: Versteegen Pauline , Barkoff Alex-Mikael , Valente Pinto Marta , van de Kasteele Jan , Knuutila Aapo , Bibi Sagida , de Rond Lia , Teräsjärvi Johanna , Sanders Katherine , de Zeeuw-Brouwer Mary-lène , Luoto Raakel , ten Hulscher Hinke , Clutterbuck Elizabeth A. , Sanders Elisabeth A. M. , Mertsola Jussi , Berbers Guy A. M. , He Qiushui , Kelly Dominic F. , Buisman Anne-Marie ,   PERISCOPE Consortium
Published: May 2022

BackgroundImmunogenicity of acellular pertussis (aP) vaccines is conventionally assessed by measuring antibody responses but antibody concentrations wane quickly after vaccination. Memory B cells, however, are critical in sustaining long-term protection and therefore may be an important factor when assessing pertussis immunity after vaccination.AimWe studied pertussis specific memory B cell (re)activation induced by an aP booster vaccination in four different age groups within three countries.Materials and methodsFrom a phase IV longitudinal interventional study, 268 participants across Finland, the Netherlands and the United Kingdom were included and received a 3-component pertussis booster vaccine: children (7-10y, n=53), adolescents (11-15y, n=66), young adults (20-34y, n=74), and older adults (60-70y, n=75). Memory B cells at baseline, day 28, and 1 year post-vaccination were measured by a pertussis toxin (Ptx), filamentous haemagglutinin (FHA), and pertactin (Prn) specific ELISpot assay. Antibody results measured previously were available for comparison. Furthermore, study participants were distributed into groups based on their baseline memory B cell frequencies, vaccine responses were monitored between these groups.ResultsGeometric mean (GM) memory B cell frequencies for pertussis antigens at baseline were low. At 28 days post-vaccination, these frequencies increased within each age group and were still elevated one year post-booster compared to baseline. Highest frequencies at day 28 were found within adolescents (GM: 5, 21, and 13, for Ptx, FHA and Prn, respectively) and lowest within older adults (GM: 2, 9, and 3, respectively). Moderate to strong correlations between memory B cell frequencies at day 28 and antibody concentrations at day 28 and 1 year were observed for Prn. Memory B cell frequencies &gt; 1 per 100,000 PBMCs at baseline were associated with significantly higher memory responses after 28 days and 1 year.ConclusionsAn aP booster vaccine (re)activated memory B cells in all age groups. Still elevated memory B cell frequencies after one year indicates enhanced immunological memory. However, antigen specific memory B cell activation seems weaker in older adults, which might reflect immunosenescence. Furthermore, the presence of circulating memory B cells at baseline positively affects memory B cell responses. This study was registered at www.clinicaltrialsregister.eu: No. 2016-003678-42.
Immunopsychiatry – Innovative Technology to Characterize Disease Activity in Autoantibody-Associated Psychiatric Diseases
Authors: Hansen Niels 
Published: May 2022

Background Anti-neural autoantibody-associated psychiatric disease is a novel field in immunopsychiatry that has been attracting attention thanks to its potentially positive therapeutic outcome and distinct prognosis compared with non-organic psychiatric disease. This review aims to describe recent novel technological developments for improving diagnostics in the field of autoantibody-related psychiatric disease.MethodsWe screened for relevant articles in PubMed for this narrative article. We focused on research methods such as neuroimaging, immune cells and inflammation markers, and molecular biomarkers in human biofluids like serum and cerebrospinal fluid and plasma proteomics.ResultsWe introduce several novel methods for investigating autoinflammation with the aim of optimizing therapies for autoantibody-associated psychiatric disease. We describe measuring the translocator protein 18kDa in activated microglia via positron emission tomography imaging, brain volumetric assessment, flow cell cytometry of cerebrospinal fluid and blood, and blood biological probes as well as psychopathological cues to help us gain insights into diagnosing inflammation and brain damage better in psychiatric patients presenting a suspected autoimmune etiology.ConclusionOur short methodological review provides an overview of recent developments in the field of autoantibody-related immunopsychiatry. More research is needed to prove their usefulness in diagnosing and treating autoantibody-associated psychiatric disease and its subtypes.
Dietary Intake and Pneumococcal Vaccine Response Among Children (5–7 Years) in Msambweni Division, Kwale County, Kenya
Authors: Migliore Eleonora , Amaitsa Vivian K. , Mutuku Francis M. , Malhotra Indu J. , Mukoko Dunstan , Sharma Anika , Kalva Prathik , Kang Amrik S. , King Charles H. , LaBeaud A. Desiree 
Published: May 2022

BackgroundVaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa.MethodsIn this study, the 10-valent pneumococcal conjugate vaccine (Synflorix® or PCV10) was administered to a child cohort (5–7 years old, n = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status. Individual food varieties were recorded and divided into 9 food groups as recommended by Food and Agriculture Organization. Anthropometric measurements, nasopharyngeal swabs and vaccine administration were performed at the initial visit. Participants were followed 4–8 weeks with a blood draw for pneumococcal IgG titers assessed by Luminex assay.FindingsChronic malnutrition was prevalent in the cohort (15% stunting, 16% underweight). Unbalanced dietary intake was observed, with mean energy intake 14% below Recommended Dietary Allowances (1,822 Kcal) for 5–7 years age range. 72% of the daily energy was derived from carbohydrates, 18% from fats and only 10% from proteins. Poor anthropometric status (stunting/underweight) was associated with low socioeconomic/educational status and younger mother/caregiver age (p &lt; 0.002). Limited intake of essential micronutrients (vitamins A, E, K) and minerals (calcium, potassium) associated with low consumption of fresh fruits, vegetables, and animal source foods (dairy, meat) was observed and correlated with poor vaccine response (p &lt; 0.001). In contrast, children who consumed higher amounts of dietary fiber, vitamin B1, zinc, iron, and magnesium had adequate vaccine response (p &lt; 0.05). Correlation between higher dietary diversity score (DDS), higher Vitamin E, K, Zinc intake and adequate vaccine response was also observed (p &lt; 0.03).InterpretationOverall, this study highlights ongoing food scarcity and malnutrition in Kenya and demonstrates the links between adequate socioeconomic conditions, adequate nutrient intake, and vaccine efficacy.
Sugar-Sweetened Beverages and Depressive and Social Anxiety Symptoms Among Children and Adolescents Aged 7–17 Years, Stratified by Body Composition
Authors: Liu Jieyu , Chen Ting , Chen Manman , Ma Ying , Ma Tao , Gao Di , Li Yanhui , Ma Qi , Chen Li , Wang Xinxin , Zhang Yi , Ma Jun , Dong Yanhui 
Published: May 2022

BackgroundRare studies investigated the associations between sugar-sweetened beverage (SSB) consumption with depressive and social anxiety symptoms among children and adolescents, particularly in different stratification of body composition, which was our purpose.MethodsA cross-sectional survey of children and adolescents aged 7–17 years was conducted in Beijing, China, in 2020, with an average age of 12.07 (SD: 3.09) years. Children's Depression Inventory (CDI) questionnaires and social anxiety scale for children (SASC) were completed in the baseline questionnaires. SSB consumption and body composition were assessed using child-reported questionnaires and a GE Healthcare Lunar iDXA dual-energy X-ray bone densitometer. Multivariate logistic regression was used to assess the associations between SSB consumption with depressive and social anxiety symptoms. Confounders were evaluated by child-reported and parental questionnaires, including age, sex, parental educational attainment, maternal smoking status, single-child status, BMI, incomes, fruit consumption, physical activity, screen time, and the frequency of fried food consumption. Stratified analyses were performed to explore whether the associations were influenced by body composition.ResultsA total of 1,311 children and adolescents, including 658 boys and 653 girls, were included in the final analysis. There were 13.96 and 29.75% of the study population with depressive and social anxiety symptoms, respectively. Overall, about 63.77% of the children and adolescents consumed SSB, and the average SSB intake was 0.35 servings per day. In the fully adjusted model, compared to participants who did not consume SSB each day, SSB consumption of ≥1 servings/day was positively associated with depressive symptoms [odds ratio (OR) = 2.28, 95% CI = 1.30–4.01] and social anxiety (OR = 1.10, 95% CI = 0.69–1.77), though the latter did not reach statistical significance. When individuals had higher body fat or lower fat-free mass (FFM) or muscle, the ORs of depressive symptoms were more evident among children and adolescents who drank SSB for ≥1 servings/day (P &lt; 0.05).ConclusionHigher consumption of SSB could be associated with increased OR of depressive symptoms in children and adolescents. The association remained robust, especially in groups with higher body fat or lower fat-free mass or muscle.
Clinical Relevance of Estrogen Reactivity in the Breast Cancer Microenvironment
Authors: Takeshita Takashi , Tokumaru Yoshihisa , Oshi Masanori , Wu Rongrong , Patel Ankit , Tian Wanqing , Hatanaka Yutaka , Hatanaka Kanako C. , Yan Li , Takabe Kazuaki 
Published: May 2022

PurposeEstrogen signals play an important role in the phenotype of estrogen receptor-positive breast cancer. However, comprehensive analyses of the effect of responsiveness to estrogen signals on the tumor microenvironment and survival in large cohorts of primary breast cancer patients have been lacking. We aimed to test the hypothesis that estrogen reactivity affects gene expression and immune cell infiltration profiles in the tumor microenvironment and survival.MethodsA total of 3,098 breast cancer cases were analyzed: 1,904 from the Molecular Taxonomy of Breast Cancer (METABRIC) cohort, 1,082 from The Cancer Genome Atlas (TCGA) cohort, and 112 from the Hokkaido University Hospital cohort. We divided the group into estrogen reactivity-high and estrogen reactivity-low groups utilizing the scores of ESTROGEN_RESPONSE_EARLY and ESTROGEN_RESPONSE_LATE in Gene Set Variation Analysis.ResultsBreast cancer with high estrogen reactivity was related to Myc targets, metabolism-related signaling, cell stress response, TGF-beta signaling, androgen response, and MTORC1 signaling gene sets in the tumor microenvironment. Low estrogen reactivity was related to immune-related proteins, IL2-STAT5 signaling, IL6-JAK-STAT3 signaling, KRAS signaling, cell cycle-related gene sets, and EMT. In addition, breast cancer with high levels of estrogen reactivity had low immune cytolytic activity and low levels of immunostimulatory cells. It also had low levels of stimulatory and inhibitory factors of the cancer immunity cycle. Patients with high estrogen reactivity were also associated with a better prognosis.ConclusionWe demonstrated the relationship between estrogen reactivity and the profiles of immune cells and gene expression, as well as survival.
Sensitization of Non-Small Cell Lung Cancer Cells to Gefitinib and Reversal of Epithelial–Mesenchymal Transition by Aloe-Emodin Via PI3K/Akt/TWIS1 Signal Blockage
Authors: Peng Minghui , Zheng Zhuifeng , Chen Shaoyang , Fang Le , Feng Rongxiu , Zhang Lijun , Tang Qingnan , Liu Xuewen 
Published: May 2022

ObjectiveTo explore the impacts of AE (aloe-emodin) in gefitinib-resistant NSCLC (non-small cell lung cancer) cells and the corresponding mechanism.MethodsPC9 and PC9-GR cells were cultured and treated by gefitinib, AE, or the combination of the two drugs. Then, viability, apoptosis, migration and invasion of cells were investigated using CCK-8, TUNEL, wound healing assay, and transwell assay, respectively. Female BALB/c nude mice were employed for the establishment of xenograft tumor models to examine the role of AE in tumor growth.ResultsPC9-GR cells showed reduced apoptosis and enhanced cell viability, migration and invasion upon treatment by gefitinib, compared with PC9 cells. E-cahherin in PC9-GR cells was down-regulated, while Vimentin, Snail2 (or Slug) and Twist1 in PC9-GR cells were up-regulated, compared with PC9 cells. Meanwhile, treatment by a combination of gefitinib and AE significantly strengthened apoptosis of PC9-GR cells, while attenuated their migration and invasion, compared with the control group or treatment by gefitinib or AE alone. WB results showed that AE could reverse EMT and activation of PI3K/AKT signalling pathway in PC9-GR cells. In vivo experiments showed that tumor growth and EMT of PC9-GR cells were dramatically repressed after treatment by a combination of AE and gefitinib. Additionally, the use of SC97 (a PI3K/Akt pathway activator) could counteract the effects of AE in gefitinib-resistant PC9 cells.ConclusionsAE could enhance the gefitinib sensitivity of PC9-GR cells and reverse EMT by blocking PI3K/Akt/TWIS1 signal pathway.
Family-Assisted Severity of Illness Monitoring for Hospitalized Children in Low-Resource Settings—A Two-Arm Interventional Feasibility Study
Authors: von Saint Andre-von Arnim Amelie O. , Kumar Rashmi K. , Clark Jonna D. , Wilfond Benjamin S. , Nguyen Quynh-Uyen P. , Mutonga Daniel M. , Zimmerman Jerry J. , Oron Assaf P. , Walson Judd L. 
Published: May 2022

IntroductionPediatric mortality remains unacceptably high in many low-resource settings, with inpatient deaths often associated with delayed recognition of clinical deterioration. The Family-Assisted Severe Febrile Illness ThERapy (FASTER) tool has been developed for caregivers to assist in monitoring their hospitalized children and alert clinicians. This study evaluates feasibility of implementation by caregivers and clinicians.MethodsRandomized controlled feasibility study at Kenyatta National Hospital, Kenya. Children hospitalized with acute febrile illness with caregivers at the bedside for 24 h were enrolled. Caregivers were trained using the FASTER tool. The primary outcome was the frequency of clinician reassessments between intervention (FASTER) and standard care arms. Poisson regression with random intercept for grouping by patient was used, adjusting for admission pediatric early warning score, age, gender. Secondary outcomes included survey assessments of clinician and caregiver experiences with FASTER.ResultsOne hundred and fifty patient/caregiver pairs were enrolled, 139 included in the analysis, 74 in the intervention, 65 in the control arm. Patients' median age was 0.9 (range 0.2–10) and 1.1 years (range 0.2–12) in intervention vs. control arms. The most common diagnoses were pneumonia (80[58%]), meningitis (58[38%]) and malaria (34 [24%]). 134 (96%) caregivers were patients' mothers. Clinician visits/hour increased with patients' illness severity in both arms, but without difference in frequency between arms (point estimate for difference −0.9%, p = 0.97). Of the 16 deaths, 8 (four/arm) occurred within 2 days of enrollment. Forty clinicians were surveyed, 33 (82%) reporting that FASTER could improve outcomes of very sick children in low-resource settings; 26 (65%) rating caregivers as able to adequately capture patients' severity of illness. Of 70 caregivers surveyed, 63 (90%) reported that FASTER training was easy to understand; all (100%) agreed that the intervention would improve care of hospitalized children and help identify sick children in their community.DiscussionWe observed no difference in recorded frequency of clinician visits with FASTER monitoring. However, the tool was rated positively by caregivers and clinicians., Implementation appears feasible but requires optimization. These feasibility data may inform a larger trial powered to measure morbidity and mortality outcomes to determine the utility of FASTER in detecting and responding to clinical deterioration in low-resource settings.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03513861.
Treated Pierre Robin Sequence Using Placed Allogenic Acellular Bone Matrix and Mandibular Distraction Osteogenesis in the Neonate
Authors: Han Tao , Ji Yi , Cui Jie , Kong Liangliang , Shi Lijun , Chen Jianbin , Shen Weimin 
Published: May 2022

ObjectiveThe aim of the study was to report our experience with placed allogenic acellular bone matrix and mandibular distraction osteogenesis in Pierre Robin sequence (PRS), and explore the role of distraction in the osteogenesis of acellular bone.Materials and MethodsA total of 428 neonates with severe PRS managed with placing allogenic acellular bone and bilateral mandibular distraction osteogenesis were included in the study. The procedure included using oblique-shaped osteotomy, fixing bilateral mandibular distractor, instantly extending a 4–6 mm gap, and placing allogenic acellular bone into the gap. The length of allogenic acellular bone was 4–5 mm. Although the surgical techniques, distraction, and consolidation periods were similar, the allogenic acellular bone matrix we placed was quite different from the traditional distraction. With the technology we used, tracheal intubation could be immediately removed, thus quickly improving breathing conditions compared to traditional methods after the surgery. The jaw extending and oral feeding could begin on the 5th day. The jaw was extended 0.6 mm twice a day until the mandible was overcorrected by 20%.ResultsAll 428 cases included in this study were successfully extubated after the operation, and the difficulty in breathing was instantly relieved. Total mandibular distraction was 15–20 mm. Oral feeding was started at 6 h to 6 days postoperatively, while hospital stay ranged from 18 to 20 days postoperatively. No major complications were reported. Medium to long-term results was good. Mandibular distractors were removed after 3 months.ConclusionsBilateral mandibular distraction osteogenesis combined with placing allogenic acellular bone in the neonate are safe and accurate procedures, which are the primary treatment options for cases of severe PRS. It can be considered that the tension of distraction can promote osteogenesis in acellular bone and thus improve distractive effect of the mandible.