bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial Dysfunction Links to Impaired Hippocampal Serotonin Release in a Mouse Model of Alzheimer’s Disease
Authors: Tian Jing , Stucky Chase Samuel , Wang Tienju , Muma Nancy A. , Johnson Michael , Du Heng 
Published: April 2023

Background: Deprivation of extracellular serotonin has been linked to cognitive decline and neuropsychiatric disturbances in Alzheimer’s disease (AD). However, despite degeneration of serotonin-producing neurons, whether serotonin release is affected in AD-sensitive brain regions is unknown. Objective: This study investigated the impact of mitochondrial dysfunction in decreased hippocampal serotonin release in AD amyloidosis mouse model 5xFAD mice. Methods: Electrochemical assays were applied to examine hippocampal serotonin release. We also employed multidisciplinary techniques to determine the role of oligomeric amyloid-β (Aβ) in hippocampal mitochondrial deficits and serotonin release deficiency. Results: 5xFAD mice exhibited serotonin release decrease and relatively moderate downregulation of serotonergic fiber density as well as serotonin content in the hippocampal region. Further experiments showed an inhibitory effect of oligomeric amyloid-β (Aβ) on hippocampal serotonin release without affecting the density of serotonergic fibers. Pharmaceutical uncoupling of mitochondrial oxidative phosphorylation (OXPHOS) disrupted hippocampal serotonin release in an ex vivo setting. This echoes the mitochondrial defects in serotonergic fibers in 5xFAD mice and oligomeric Aβ-challenged primary serotonergic neuron cultures and implicates a link between mitochondrial dysfunction and serotonin transmission defects in AD-relevant pathological settings. Conclusion: The most parsimonious interpretation of our findings is that mitochondrial dysfunction is a phenotypic change of serotonergic neurons, which potentially plays a role in the development of serotonergic failure in AD-related conditions.
Vacunas conjugadas contra neumococo en pediatría, su impacto en la Salud Pública
Authors: Ospina-Henao Sebastián , Torres Juan Pablo , Brea Jose , Ávila-Agüero Maria L. 
Published: April 2023

Streptococcus pneumoniae forma parte de la flora bacteriana normal de la mucosa nasal y faríngea, coloniza principalmente la nasofaringe y provoca que esta portación preceda a la enfermedad neumocócica, convirtiéndose así en la principal fuente de propagación entre las personas, especialmente en niños. A partir del año 1983, fecha en que se autorizó la primera vacuna antineumocócica de 23 componentes, se han desarrollado diferentes vacunas conjugadas, según los serotipos circulantes y causantes de enfermedades neumocócicas invasivas (ENI), de esta manera, se ha logrado disminuir en gran medida la incidencia y mortalidad de las enfermedades asociadas a neumococo. En noviem- bre del 2021, un grupo de expertos llevó a cabo una reunión virtual para analizar y actualizar el impacto que estas vacunas neumocócicas han generado en la salud pública de los países, especialmente durante la pandemia de la COVID-19, y como parte de las recomendaciones que surgieron se planteó que, ante el reemplazo de serotipos luego de la introducción de las vacunas antineumocócicas conjugadas (PCV) en los esquemas nacionales, es necesario buscar alternativas en vacunas independientes del serotipo, y de igual manera se deben unir esfuerzos para fortalecer la vigilancia de los serotipos, enfatizando en los no incluidos en las vacunas actuales. El objetivo de este reporte es comunicar las conclusiones del grupo de expertos que en noviembre 2021 analizó el impacto de las vacunas neumocócicas en la salud pública de los países, para generar recomendaciones aplicables en Latinoamérica.
ANALISIS DANA HIBAH PROGRAM DESA/KELURAHAN MANDIRI ANGGUR MERAH DI KECAMATAN FATULEU KABUPATEN KUPANG PROVINSI NUSA TENGGARA TIMUR (STUDI KASUS PADA DESA NAUNU)
Authors: Manane Desmon Dedikson 
Published: April 2023

ABSTRAK
Masalah dalam penelitian ini adalah (1) Bagaimana gambaran kredit modal kerja, lapangan kerja dan derajat kesehatan dan tingkat kemiskinan anggota kelompok masyarakat peneriman manfaat Program Desa/Kelurahan Mandiri Anggur Merah Desa Naunu? (2) Apakah kredit modal kerja, lapangan kerja dan derajat kesehatan masyarakat berpengaruh signifikan terhadap tingkat kemiskinan anggota kelompok masyarakat peneriman manfaat Program Desa/Kelurahan Mandiri Anggur Merah Desa Naunu? (3) Apakah kredit modal kerja, lapangan kerja, dan derajat kesehatan secara simultan berpengaruh signifikan terhadap tingkat kemiskinan anggota kelompok masyarakat penerima manfaat Program Desa/Kelurahan Mandiri Anggur Merah Desa Naunu?
Data dikumpulkan dari 60 responden dengan menggunakan sampel jenuh. Data kemudian diolah dan dianalisis dengan menggunakan statistik deskriptif dan statistik inferensial. Hasil analisis statistik deskriptif menunjukan bahwa tingkat kemiskinan masyarakat (60,33%) cukup baik, kredit modal kerja (57,00%) cukup baik, lapangan kerja (57,56%) cukup baik, dan derajat kesehatan (58,44%) cukup baik. Hasil uji t menunjukan bahwa secara parsial, variabel kredit modal kerja, lapangan kerja, dan derajat kesehatan berpengaruh signifikan terhadap penurunan tingkat kemiskinan. Hal ini terlihat dari nilai t pada variabel kredit modal kerja 3,777 pada signifikansi 0,000, lapangan kerja 2,743 pada signifikansi 0,008, derajat kesehatan 3,164 pada signifikansi 0.003. hasil uji F menunjukan bahwa secara simultan variabel kredit modal kerja, lapangan kerja, dan derajat kesehatan berpengaruh terhadap tingkat kemiskinan. Hal ini terlihat dari nilai F sebesar 13,840 pada signifikansi 0,000, dan hasil koefisien determinan (R2) menunjukan bahwa kredit modal kerja, lapangan kerja, dan derajat kesehatan memberikan sumbangan sebesar 42,6% terhadap tingkat kemiskinan masyarakat sedangkan sisanya sebesar 57,4% disumbangkan oleh variabel lain yang tidak termasuk dalam penelitian ini.
Berdasarkan hasil penelitian ini, disarankan kepada anggota kelompok masyarakat agar dapat memanfaatkan kredit modal kerja yang disediakn oleh pemerintah dengan baik dalam peluasan lapangan kerja, serta meningkatkan derajat kesehatan. Sedangkan bagi pemerintah khusunya Pemerintah Desa Naunu agar dapat meningkatkan kredit modal kerja, lapangan kerja, dan derajat kesehatan dengan menambahkan anggaran dari dana desa melalui bidang pemberdayaan masyarakat dalam penurunan tingkat kemiskinan.
Ecology of food waste chain-elongating microbiome
Authors: Crognale Simona , Massimi Alessio , Sbicego Michela , Braguglia Camilla Maria , Gallipoli Agata , Gazzola Giulio , Gianico Andrea , Tonanzi Barbara , Di Pippo Francesca , Rossetti Simona 
Published: April 2023

Microbial chain elongation has emerged as a valuable bioprocess for obtaining marketable products, such as medium chain fatty acids usable in several industrial applications, from organic waste. The understanding of the microbiology and microbial ecology in these systems is crucial to apply these microbiomes in reliable production processes controlling microbial pathways to promote favourable metabolic processes, which will in turn increase product specificity and yields. In this research, the dynamics, cooperation/competition and potentialities of bacterial communities involved in the long-term lactate-based chain elongation process from food waste extract were evaluated under different operating conditions by DNA/RNA amplicon sequencing and functional profile prediction. The feeding strategies and the applied organic loading rates strongly affected the microbial community composition. The use of food waste extract promoted the selection of primary fermenters (i.e., Olsenella, Lactobacillus) responsible for the in situ production of electron donors (i.e., lactate). The discontinuous feeding and the organic loading rate 15 gCOD L-1 d-1 selected the best performing microbiome in which microbes coexist and cooperate to complete the chain elongation process. Both at DNA and RNA level, this microbiome was composed by the lactate producer Olsenella, the short chain fatty acids producers Anaerostipes, Clostridium sensu stricto 7, C. sensu stricto 12, Corynebacterium, Erysipelotrichaceae UCG-004, F0332, Leuconostoc, and the chain elongator Caproiciproducens. This microbiome also showed the highest predicted abundance of short-chain acyl-CoA dehydrogenase, the functional enzyme responsible for the chain elongation process. The combined approach herein used allowed to study the microbial ecology of chain elongation process from food waste by identifying the main functional groups, establishing the presence of potential biotic interactions within the microbiomes, and predicting metabolic potentialities. This study provided pivotal indications for the selection of high-performance microbiome involved in caproate production from food waste that can serve as a basis for further improving system performance and engineering the process scale-up.
Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators
Authors: Kulka Marianna , Wagner Ashley , Cho Jae-Young , Alam Syed Benazir , Santos Joy Ramielle , Jovel Juan , Karamchand Leshern , Marcet-Palacios Marcelo 
Published: April 2023

Introduction: Mast cells are highly granulated tissue-resident leukocytes that require a three-dimensional matrix to differentiate and mediate immune responses. However, almost all cultured mast cells rely on two-dimensional suspension or adherent cell culture systems, which do not adequately reflect the complex structure that these cells require for optimal function.Methods: Crystalline nanocellulose (CNC), consisting of rod-like crystals 4–15 nm in diameter and 0.2–1 µm in length, were dispersed in an agarose matrix (12.5% w/v), and bone marrow derived mouse mast cells (BMMC) were cultured on the agarose/CNC composite. BMMC were activated with the calcium ionophore A23187 or immunoglobulin E (IgE) and antigen (Ag) to crosslink high affinity IgE receptors (FcεRI).Results: BMMC cultured on a CNC/agarose matrix remained viable and metabolically active as measured by reduction of sodium 3′-[1-[(phenylamino)-carbony]-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT), and the cells maintained their membrane integrity as analyzed by measuring the release of lactate dehydrogenase (LDH) and propidium iodide exclusion by flow cytometry. Culture on CNC/agarose matrix had no effect on BMMC degranulation in response to IgE/Ag or A23187. However, culture of BMMC on a CNC/agarose matrix inhibited A23187-and IgE/Ag-activated production of tumor necrosis factor (TNF) and other mediators such as IL-1β, IL-4, IL-6, IL-13, MCP-1/CCL2, MMP-9 and RANTES by as much as 95%. RNAseq analysis indicated that BMMC expressed a unique and balanced transcriptome when cultured on CNC/agarose.Discussion: These data demonstrate that culture of BMMCs on a CNC/agarose matrix promotes cell integrity, maintains expression of surface biomarkers such as FcεRI and KIT and preserves the ability of BMMC to release pre-stored mediators in response to IgE/Ag and A23187. However, culture of BMMC on CNC/agarose matrix inhibits BMMC production of de novo synthesized mediators, suggesting that CNC may be altering specific phenotypic characteristics of these cells that are associated with late phase inflammatory responses.
Clinical application value of metagenomic next-generation sequencing in the diagnosis of central nervous system infections
Authors: Liu Ying , Zhu Weiwei , Jiao Mengfan , Guo Wenhu , Luo Yonggang 
Published: April 2023

Objectives: The purpose of this study is to evaluate the clinical application value of metagenomic next-generation sequencing (mNGS) in central nervous system (CNS) infections.Methods: Both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with CNS infections retrospectively analyzed the efficacy of mNGS in this cohort and were ultimately compared with a clinical diagnosis.Results: A total of 94 cases consistent with CNS infections were included in the analysis. The positive rate for mNGS is 60.6% (57/94), which is significantly higher than 20.2% (19/94; p &lt; 0.01) detected using conventional methods. mNGS detected 21 pathogenic strains that could not be detected by routine testing. Routine tests were positive for two pathogens but negative for mNGS. The sensitivity and specificity of mNGS in the diagnosis of central nervous system infections were 89.5% and 44%, respectively, when compared with traditional tests. At discharge, 20 (21.3%) patients were cured, 55 (58.5%) patients showed improvements, five (5.3%) patients did not recover, and two (2.1%) patients died.Conclusion: mNGS has unique advantages in the diagnosis of central nervous system infections. mNGS tests can be performed when patients are clinically suspected of having a central nervous system infection but no pathogenic evidence.
Altered serum metabolome associated with vascular calcification developed from CKD and the critical pathways
Authors: Tan Ruyu , Ou Santao , Kang Ting , Wu Weihua , Xiong Lin , Zhu Tingting , Zhang Liling 
Published: April 2023

IntroductionVascular calcification (VC) is more likely to be detected in the chronic kidney disease (CKD) population. The mechanism of VC development from CKD is different from that for simple VC and has always been a major research area. The aim of this study was to detect alterations in the metabolome during development of VC in CKD and to identify the critical metabolic pathways and metabolites involved in its pathogenesis.MethodsRats in the model group were given an adenine gavage combined with a high-phosphorus diet to imitate VC in CKD. The aorta calcium content was measured and used to divide the model group into a VC group and non-vascular calcification group (non-VC group). The control group was fed a normal rat diet and given a saline gavage. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to determine the altered serum metabolome in the control, VC, and non-VC groups. The identified metabolites were mapped into the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (https://www.genome.jp/kegg/) for pathway and network analyses.ResultThere were 14 metabolites that changed significantly in the VC group, with three metabolic pathways playing critical roles in the pathogenesis of VC in CKD: steroid hormone biosynthesis; valine, leucine and isoleucine biosynthesis; and pantothenate and CoA biosynthesis.ConclusionOur results indicated changes in the expression of steroid sulfatase and estrogen sulfotransferase, and down-regulation of the in situ synthesis of estrogens in the VC group. In conclusion, the serum metabolome alters significantly during the pathogenesis of VC in CKD. The key pathways, metabolites, and enzymes we identified are worth further study and may become a promising therapeutic target for the treatment of VC in CKD.
The value of myocardial work in the estimation of left ventricular systolic function in patients with coronary microvascular disease: A study based on adenosine stress echocardiography
Authors: Liu Quande , Li Qimou , Wan Xiaoyu , Xu Mingjun , Pan Jichen , Zhang Yu , Li Mengmeng , Zhang Mei 
Published: April 2023

BackgroundCoronary microvascular dysfunction (CMD) is associated with increased cardiovascular events in patients with angina with non-obstructive coronary (ANOCA), especially heart failure. Conventional echocardiography is difficult to identify early alterations in cardiac function due to CMD.MethodsWe recruited 78 ANOCA patients. All patients underwent conventional echocardiography examination, adenosine stress echocardiography and examination of coronary flow reserve (CFR) by transthoracic echocardiography. Based on the CFR results, patients were divided into the CMD group (CFR &lt; 2.5) and the non-CMD group (CFVR ≥ 2.5). Demographic data, conventional echocardiographic parameters, two-dimensional speckle-tracking echocardiography (2D-STE) parameters and myocardial work (MW) were compared between the two groups at rest and at stress. Logistic regression was used to analyze the factors associated with CMD.ResultsThere was no significant difference in conventional echocardiography parameters, 2D-STE related indices or MW at rest between the two groups. Global work index (GWI), global contractive work (GCW), and global work efficiency (GWE) were lower in the CMD group than in the non-CMD group at stress (p = 0.040, 0.044, &lt;0.001, respectively), but global waste work (GWW) and peak strain dispersion (PSD) were higher (both p &lt; 0.001). GWI and GCW were associated with systolic blood pressure, diastolic blood pressure, product of heart rate and blood pressure, GLS and coronary flow velocity. While GWW was mainly correlated with PSD, GWE was correlated with PSD and GLS. In the non-CMD group, the responses to adenosine was mainly manifested as an increase in GWI, GCW and GWE (p = 0.001, 0.001, 0.009, respectively) and a decrease in PSD and GWW (p = 0.001, 0.015, respectively). In the CMD group, the response to adenosine was mainly manifested as an increase in GWW and a decrease in GWE (p = 0.002, and 0.006, respectively). In the multivariate regression analysis, we found that ΔGWW (difference in GWW before vs. after adenosine stress) and ΔPSD (difference in PSD before vs. after adenosine stress) were independent factors associated with CMD. The ROC curves showed that the composite prediction model consisting of ΔGWW and ΔPSD had excellent diagnostic value for CMD (area under the curve = 0.913).ConclusionIn the present study, we found that CMD caused deterioration of myocardial work in ANOCA patients under adenosine stress, and that increased cardiac contraction asynchrony and wasted work may be the main changes caused by CMD.
Consistent long-term practice leads to consistent improvement: Benefits of self-managed therapy for language and cognitive deficits using a digital therapeutic
Authors: Liu Hantian , Cordella Claire , Ishwar Prakash , Betke Margrit , Kiran Swathi 
Published: April 2023

BackgroundAlthough speech-language therapy (SLT) is proven to be beneficial to recovery of post-stroke aphasia, delivering sufficiently high amounts of dosage remains a problem in real-world clinical practice. Self-managed SLT was introduced to solve the problem. Previous research showed in a 10-week period, increased dosage frequency could lead to better performance, however, it is uncertain if dosage still affects performance over a longer period of practice time and whether gains can be seen following practice over several months.ObjectiveThis study aims to evaluate data from a health app (Constant Therapy) to investigate the relationship between dosage amount and improvements following a 30-week treatment period. Two cohorts of users were analyzed. One was comprised of patients with a consistent average weekly dosage amount and the other cohort was comprised of users whose practice had higher variability.MethodsWe conducted two analyses with two cohorts of post-stroke patients who used Constant Therapy. The first cohort contains 537 “consistent” users, while the second cohort contains 2,159. The 30-week practice period was split into three consecutive 10-week practice windows to calculate average dosage amount. In each 10-week practice period, patients were grouped by their average dosage into low (0–15 min/week), medium (15–40 min/week) and moderate dosage (greater than 40 min/week) groups. Linear mixed-effects models were employed to evaluate if dosage amount was a significant factor affecting performance. Pairwise comparison was also applied to evaluate the slope difference between groups.ResultsFor the consistent cohort, medium (β = .002, t17,700 = 7.64, P &lt; .001) and moderate (β = .003, t9,297 = 7.94, P &lt; .001) dosage groups showed significant improvement compared to the low dosage group. The moderate group also showed greater improvement compared to the medium group. For the variable cohort in analysis 2, the same trend was shown in the first two 10-week windows, however, in weeks 21–30, the difference was insignificant between low and medium groups (β = .001, t = 1.76, P = .078).ConclusionsThis study showed a higher dosage amount is related to greater therapy outcomes in over 6 months of digital self-managed therapy. It also showed that regardless of the exact pattern of practice, self-managed SLT leads to significant and sustained performance gains.
Association of the gut microbiota with coronary artery disease and myocardial infarction: A Mendelian randomization study
Authors: Wang Dan , Chen Xiaoyan , Li Zhen , Luo Ying 
Published: April 2023

Background: Previous studies have indicated that the gut microbiota (GM) is associated with coronary artery disease (CAD), but the causality of these associations remains unestablished due to confounding factors and reverse causality. We conducted Mendelian randomization study (MR) to determine the causal effect of the specific bacterial taxa on CAD/myocardial infarction (MI) and identify the mediating factors involved.Methods: Two-sample MR, multivariable MR (MVMR) and mediation analysis were performed. Inverse-variance weighting (IVW) was the main method used to analyze causality, and sensitivity analysis was used to verify the reliability of the study. Causal estimates from CARDIoGRAMplusC4D and FinnGen databases were combined using the meta-analysis method, and repeated validation was conducted based on the UK Biobank (UKB) database. Confounders that may affect the causal estimates were corrected by MVMP and the potential mediation effects were investigated by using mediation analysis.Results: The study suggested that increased abundance of the RuminococcusUCG010 genus leads to a lower risk of CAD (OR, 0.88; 95% CI, 0.78, 1.00; p = 2.88 × 10−2) and MI (OR, 0.88; 95% CI, 0.79, 0.97; p = 1.08 × 10−2), with consistent results in both meta-analysis (CAD: OR, 0.86; 95% CI, 0.78, 0.96; p = 4.71 × 10−3; MI: OR, 0.82; 95% CI, 0.73, 0.92; p = 8.25 × 10−4) and repeated analysis of the UKB dataset (CAD: OR, 0.99; 95% CI, 0.99, 1.00, p = 2.53 × 10−4; MI: OR, 0.99; 95% CI, 0.99, 1.00, p = 1.85 × 10–11). Based on multiple databases, T2DM was proved as a mediating factor in the causal effect of RuminococcusUCG010 and CAD/MI, with an average mediation effect proportion of 20% on CAD and 17% on MI, respectively.Conclusion: This MR study provided suggestive genetic evidence that the higher the RuminococcusUCG010 abundance is, the lower the risk of CAD and MI, with T2DM playing a mediating effect. This genus may become a novel target in strategies for treating and preventing CAD and MI.