bluuebunny/crossref_metadata_2025 huggingface dataset:
Sound board's Frequency Response Analysis of Classical Guitars
Authors: Romero Romero Milton Ernesto , Pedrosa Salgado Rafael , Mazina Martins Evandro
Published: September 2023

The instrument's sound quality assessment is an arduous task to be performed computationally. This work aims to compare high-quality sound characteristics among instruments. The impulse response of the guitar is recording in the time domain and, by means of the Fourier and Continuous Wavelet Transforms the characteristics among high-quality guitars, in the frequency domain, are shown. To discriminate high quality, through experimentation, the criteria are: 1) tuning of notes, sound projection and definition of notes; 2) sound balance at all frequencies and timbre. Comparison of the frequency response (intensity, density, shape, range) gives a good intuition regarding sound quality of the instruments that shares similar characteristics, according to the criteria defined. Note that, among the high-quality classical guitars, it is not possible to define what is better sound-wise due to the fact that high-quality instruments are hearing-perceptual defined, therefore, depends on the criteria of the musician.
Intra-articular delivery of micronized dehydrated human amnion/chorion membrane reduces degenerative changes after onset of post-traumatic osteoarthritis
Authors: Lin Angela S. P. , Reece David S. , Thote Tanushree , Sridaran Sanjay , Stevens Hazel Y. , Willett Nick J. , Guldberg Robert E.
Published: September 2023

Background: Micronized dehydrated human amnion/chorion membrane (mdHACM) has reduced short term post-traumatic osteoarthritis (PTOA) progression in rats when delivered 24 h after medial meniscal transection (MMT) and is being investigated for clinical use as a disease modifying therapy. Much remains to be assessed, including its potential for longer-term therapeutic benefit and treatment effects after onset of joint degeneration.

Objectives: Characterize longer-term effects of acute treatment with mdHACM and determine whether treatment administered to joints with established PTOA could slow or reverse degeneration. Hypotheses: Acute treatment effects will be sustained for 6 weeks, and delivery of mdHACM after onset of joint degeneration will attenuate structural osteoarthritic changes.

Methods: Rats underwent MMT or sham surgery (left leg). mdHACM was delivered intra-articularly 24 h or 3 weeks post-surgery (n = 5–7 per group). Six weeks post-surgery, animals were euthanized and left tibiae scanned using equilibrium partitioning of an ionic contrast agent microcomputed tomography (EPIC-µCT) to structurally quantify joint degeneration. Histology was performed to examine tibial plateau cartilage.

Results: Quantitative 3D µCT showed that cartilage structural metrics (thickness, X-ray attenuation, surface roughness, exposed bone area) for delayed mdHACM treatment limbs were significantly improved over saline treatment and not significantly different from shams. Subchondral bone mineral density and thickness for the delayed treatment group were significantly improved over acute treated, and subchondral bone thickness was not significantly different from sham. Marginal osteophyte degenerative changes were decreased with delayed mdHACM treatment compared to saline. Acute treatment (24 h post-surgery) did not reduce longer-term joint tissue degeneration compared to saline. Histology supported µCT findings and further revealed that while delayed treatment reduced cartilage damage, chondrocytes displayed qualitatively different morphologies and density compared to sham.

Conclusion: This study provides insight into effects of intra-articular delivery timing relative to PTOA progression and the duration of therapeutic benefit of mdHACM. Results suggest that mdHACM injection into already osteoarthritic joints can improve joint health, but a single, acute mdHACM injection post-injury does not prevent long term osteoarthritis associated with meniscal instability. Further work is needed to fully characterize the durability of therapeutic benefit in stable osteoarthritic joints and the effects of repeated injections.
Supramolecular assembly of coumarin 7 with sulfobutylether-β-cyclodextrin for biomolecular applications
Authors: Gayathry T. C. , Gaur Monika , Mishra Lopamudra , Mishra Monalisa , Barooah Nilotpal , Bhasikuttan Achikanath C. , Mohanty Jyotirmayee
Published: September 2023

Coumarins, in general, exhibit a wide range of photophysical characteristics and are highly sensitive to their microenvironment, and, therefore, their fluorescence characteristics have attracted immense attention as sensors in chemical and biological systems. In the present study, the supramolecular interaction of a bichromophoric coumarin dye, namely, Coumarin 7 (C7) with sulfobutylether-β-cyclodextrin (SBE7βCD) macrocyclic host at different pH conditions has been investigated by using optical spectroscopic techniques such as absorption, steady-state and time-resolved emissions, and circular dichroism measurements and compared with that of βCD. Considerable enhancement in the fluorescence intensity and lifetime of C7 on complexation with SBE7βCD proposes that non-radiative processes like TICT behavior are strictly hindered due to the confinement in the host cavity experienced by the C7 dye. The increase in the rotational correlation time evaluated from the fluorescence anisotropy decay kinetics further confirms the formation of tightly bound inclusion complexes. The binding constant values reveal that the monocationic form of dye at pH 3 shows ∼3 times stronger interaction with SBE7βCD than the neutral form of dye at pH 7 due to strong electrostatic cation-anion interaction. SBE7βCD:C7 exhibits an improved photostability and an upward pKa shift of 0.4 unit compared to the contrasting downward pKa shift of 0.5 with the βCD. The enhanced fluorescence yield and increased photostability have been exploited for bioimaging applications, and better images were captured by staining the Drosophila fly gut with the SBE7βCD:C7 complex. The enhancement in the binding interaction and the emission intensity were found to be responsive to external stimuli such as small competitive binders or metal ions and nearly quantitative dissociation of the complex was demonstrated to release the dye and would find stimuli-responsive applications.
Analysis of classical techniques precision on the measurement of cellulose moisture gain/loss
Authors: Cichosz Stefan , Masek Anna , Dems-Rudnicka Katarzyna
Published: September 2023

The precision of the four classical techniques (Karl-Fischer titration, (thermo)gravimetric method, Fourier-transform infrared (FT-IR) and near infrared (NIR) spectroscopies) commonly used in the analysis of cellulose moisture absorption/desorption has been deeply investigated regarding the reproducibility of these processes. Based on multiple repeated experiments, cellulose water content values obtained with Karl-Fischer titration and (thermo)gravimetric method were plotted as a function of time. Then, the cautious peak-by-peak analysis of the absorbance and wavenumber shifts visible in IR spectra has been carried out. The collected data was described using boxplots that provided valuable information on the experimental points spread. It has been successfully proven that gravimetric methods allow for precise drawing of moisture absorption and desorption curves, while Karl-Fischer titration, ATR FT-IR and NIR techniques provide the possibility of the moisture absorption/desorption processes description by linear mathematical models (R2 >90%). Therefore, this study provides a systematic comparison between various analytical methods.
The performance of tongue swabs for detection of pulmonary tuberculosis
Authors: Ealand Christopher S. , Sewcharran Astika , Peters Julian S. , Gordhan Bhavna G. , Kamariza Mireille , Bertozzi Carolyn R. , Waja Ziyaad , Martinson Neil A. , Kana Bavesh D.
Published: September 2023

Introduction

Oral and/or tongue swabs have demonstrated ability to detect Mycobacterium tuberculosis (Mtb) in adults with pulmonary tuberculosis (TB). Swabs provide useful alternative specimens for diagnosis of TB using molecular assays however, the diagnostic pickup by culture requires further improvement and development. Several studies identified the presence of differentially culturable tubercle bacilli (DCTB) populations in a variety of clinical specimens. These organisms do not grow in routine laboratory media and require growth factors in the form of culture filtrate (CF) from logarithmic phase cultures of Mtb H37Rv.

Methods

Herein, we compared the diagnostic performance of sputum and tongue swabs using Mycobacterial Growth Indicator Tube (MGIT) assays, Auramine smear, GeneXpert and DCTB assays supplemented with or without CF.

Results

From 89 eligible participants, 83 (93%), 66 (74%) and 79 (89%) were sputum positive by MGIT, smear and GeneXpert, respectively. The corresponding tongue swabs displayed a lower sensitivity with 39 (44%), 2 (2.0%) and 18 (20%) participants respectively for the same tests. We aimed to improve the diagnostic yield by utilizing DCTB assays. Sputum samples were associated with a higher positivity rate for CF-augmented DCTB at 82/89 (92%) relative to tongue swabs at 36/89 (40%). Similarly, sputum samples had a higher positivity rate for DCTB populations that were CF-independent at 64/89 (72%) relative to tongue swabs at 26/89 (29%). DCTB positivity increased significantly, relative to MGIT culture, for tongue swabs taken from HIV-positive participants. We next tested whether the use of an alternative smear stain, DMN-Trehalose, would improve diagnostic yield but noted no substantial increase.

Discussion

Collectively, our data show that while tongue swabs yield lower bacterial numbers for diagnostic testing, the use of growth supplementation may improve detection of TB particularly in HIV-positive people but this requires further interrogation in larger studies.
Dysbiosis of vaginal and cervical microbiome is associated with uterine fibroids
Authors: Mao Xuetao , Chen Hao , Peng Xuan , Zhao Xingping , Yu Zheng , Xu Dabao
Published: September 2023

Dysbiosis of the female reproductive tract is closely associated with gynecologic diseases. Here, we aim to explore the association between dysbiosis in the genital tract and uterine fibroids (UFs) to further provide new insights into UF etiology. We present an observational study to profile vaginal and cervical microbiome from 29 women with UFs and 38 healthy women, and 125 samples were obtained and sequenced. By comparing the microbial profiles between different parts of the reproductive tract, there is no significant difference in microbial diversity between healthy subjects and UF patients. However, alpha diversity of UF patients was negatively correlated with the number of fibroids. Increased Firmicutes were observed in both the cervical and vaginal microbiome of UF patients at the phylum level. In differential analysis of relative abundance, some genera were shown to be significantly enriched (e.g., Erysipelatoclostridium, Mucispirillum, and Finegoldia) and depleted (e.g., Erysipelotrichaceae UCG-003 and Sporolactobacillus) in UF patients. Furthermore, the microbial co-occurrence networks of UF patients showed lower connectivity and complexity, suggesting reduced interactions and stability of the cervical and vaginal microbiota in UF patients. In summary, our findings revealed the perturbation of microbiome in the presence of UFs and a distinct pattern of characteristic vaginal and cervical microbiome involved in UFs, offering new options to further improve prevention and management strategies.
Progressive alterations of left atrial and ventricular volume and strain across chronic kidney disease stages: a speckle tracking echocardiography study
Authors: Nguyen Hoai Thi Thu , Do Chien Van , Dang Dieu Thi Vu , Do Loi Doan , Doan Linh Huu , Dang Ha Thi Viet
Published: September 2023

Background

It has been a scarcity of evidence regarding differences in left ventricular (LV) and left atrial (LA) size and strain changes across stages of chronic kidney disease (CKD) and which echocardiographic parameters could be utilized to predict the decline of glomerular filtration rate (GFR).

Objectives

This study aimed to evaluate the alterations of LV and LA strain across the reduction of renal function and potential echocardiographic parameters which could be correlated with the GFR decline among patients with CKD.

Method

A cross-sectional study was conducted on 169 CKD patients at Bach Mai General Hospital, Hanoi, Vietnam from April to November 2022. Demographic, clinical and laboratory characteristics of patients were collected. Transthoracic echocardiography was performed to measure LV and LA size and strains. Jonckheere-Terpstra test was used to measure the tendency of change. Multivariate linear regression models were performed to find associations between different echocardiographic parameters and renal function reduction.

Results

The number of patients with CKD stages 1, 2, 3, 4, and 5 was 21 (12.4%), 28 (16.6%), 27 (16.0%), 22 (13.0%) and 71 (42.0%), respectively. CKD severity was positively associated with LV diastolic and systolic diameters, LV mass, E/e' ratio, and maximal tricuspid regurgitation velocity (TR max), and negatively correlated with the LV global longitudinal strain. Higher severity of CKD stage was associated with higher LA diameter, LA strain, and volume in four and two-chamber views, and lower LA reservoir and conduit function. Left ventricular mass (β = 0.068), ejection fraction (β = 0.112) and left atrial reservoir (β = −0.077) were associated with reduced GFR.

Conclusion

Left ventricular mass, ejection fraction, and atrial longitudinal strain by STE should be done at the earlier stages of CKD patients for better follow-up of GFR decline.
Development of a convenient and effective hypertension risk prediction model and exploration of the relationship between Serum Ferritin and Hypertension Risk: a study based on NHANES 2017—March 2020
Authors: Guo Shuang , Ge Jiu-Xin , Liu Shan-Na , Zhou Jia-Yu , Li Chang , Chen Han-Jie , Chen Li , Shen Yu-Qiang , Zhou Qing-Li
Published: September 2023

Background

Hypertension is a major public health problem, and its resulting other cardiovascular diseases are the leading cause of death worldwide. In this study, we constructed a convenient and high-performance hypertension risk prediction model to assist in clinical diagnosis and explore other important influencing factors.

Methods

We included 8,073 people from NHANES (2017—March 2020), using their 120 features to form the original dataset. After data pre-processing, we removed several redundant features through LASSO regression and correlation analysis. Thirteen commonly used machine learning methods were used to construct prediction models, and then, the methods with better performance were coupled with recursive feature elimination to determine the optimal feature subset. After data balancing through SMOTE, we integrated these better-performing learners to construct a fusion model based for predicting hypertension risk on stacking strategy. In addition, to explore the relationship between serum ferritin and the risk of hypertension, we performed a univariate analysis and divided it into four level groups (Q1 to Q4) by quartiles, with the lowest level group (Q1) as the reference, and performed multiple logistic regression analysis and trend analysis.

Results

The optimal feature subsets were: age, BMI, waist, SBP, DBP, Cre, UACR, serum ferritin, HbA1C, and doctors recommend reducing salt intake. Compared to other machine learning models, the constructed fusion model showed better predictive performance with precision, accuracy, recall, F1 value and AUC of 0.871, 0.873, 0.871, 0.869 and 0.966, respectively. For the analysis of the relationship between serum ferritin and hypertension, after controlling for all co-variates, OR and 95% CI from Q2 to Q4, compared to Q1, were 1.396 (1.176–1.658), 1.499 (1.254–1.791), and 1.645 (1.360–1.989), respectively, with P < 0.01 and P for trend <0.001.

Conclusion

The hypertension risk prediction model developed in this study is efficient in predicting hypertension with only 10 low-cost and easily accessible features, which is cost-effective in assisting clinical diagnosis. We also found a trend correlation between serum ferritin levels and the risk of hypertension.
Observation and simulation study on the rapid intensification mechanism of Typhoon “Mekkhala” (2006)
Authors: Chen Dehua , Jiang Yongcheng , Huang Xin , Xun Aiping , Dai Huaning , Zhang Hanyun
Published: September 2023

Based on Doppler Weather radar observations and numerical simulations applying the Weather Research and Forecasting (WRF) system, this study focused on the rapid intensification (RI) of Typhoon “Mekkhala” (2006) in the inshore area in 2020. The simulated track of the typhoon relatively matched with the observation, with a slight eastward bias compared to the observed track. During the phase of RI, there was a slight weakening of vertical wind shear between 200–500 hPa. The temporary decrease in vertical wind shear became a favorable factor for the intensification of the typhoon. In general, vertical wind shear of the lower atmosphere is the key to supporting the RI of Typhoon Mekkhala. In the middle troposphere, the southward component of the vertical wind shear suddenly increases, indicates that the inflow of southern wind to the core of the typhoon had strengthened. Thus, the strengthening of the moisture transport by enhanced southern wind, contributed to the intensification of the typhoon. During the intensification of the typhoon, the low-level vorticity was significantly enhanced, and the high vorticity values expanded from the lower to higher troposphere. The vertical distribution of vorticity transformed from symmetry to asymmetry. The development of secondary circulation on both sides of the typhoon is a dynamic factor for intensification.
Early warning technique research of surface subsidence for safe mining in underground goaf in Karst Plateau zone
Authors: Zhe Yalei , Hou Kepeng , Niu Xiangdong , Liang Wei
Published: September 2023

Underground mining in Karst Plateau landform area may cause the loss of support for the upper rock stratum, resulting in rock collapse and large-scale subsidence of the ground surface. Also, the formation of a large-scale goafs may further lead to geo-hazards such as collapse, water gushing, slope instability and so on in the area. To reduce the impact of goaf settlement on local strata stability, this paper established a standardized safe mining detection model for goafs based on the geological safety characteristics of mining goafs. With reference to the statistical analysis of the geological conditions in the mining area, a numerical model with 358 goafs and the proposed mining area was established using FLAC3D numerical software. The surface subsidence and variations of plastic zone in the mining area were comprehensively analyzed. The results indicated that there was a correlation between the stability of the mining area and the geological occurrence conditions of the goafs. By quantitatively taking the values from standardized safety mining detection models, the standardized safety mining detection and warning technique was finally established. The findings can provide technical guidance for safety detection and early warning in the whole process of underground goaf mining in Karst Plateau karst development zone.
Intra-FCY1: a novel system to identify mutations that cause protein misfolding
Authors: Quan N. , Eguchi Y. , Geiler-Samerotte K.
Published: September 2023

Protein misfolding is a common intracellular occurrence. Most mutations to coding sequences increase the propensity of the encoded protein to misfold. These misfolded molecules can have devastating effects on cells. Despite the importance of protein misfolding in human disease and protein evolution, there are fundamental questions that remain unanswered, such as, which mutations cause the most misfolding? These questions are difficult to answer partially because we lack high-throughput methods to compare the destabilizing effects of different mutations. Commonly used systems to assess the stability of mutant proteins in vivo often rely upon essential proteins as sensors, but misfolded proteins can disrupt the function of the essential protein enough to kill the cell. This makes it difficult to identify and compare mutations that cause protein misfolding using these systems. Here, we present a novel in vivo system named Intra-FCY1 that we use to identify mutations that cause misfolding of a model protein [yellow fluorescent protein (YFP)] in Saccharomyces cerevisiae. The Intra-FCY1 system utilizes two complementary fragments of the yeast cytosine deaminase Fcy1, a toxic protein, into which YFP is inserted. When YFP folds, the Fcy1 fragments associate together to reconstitute their function, conferring toxicity in media containing 5-fluorocytosine and hindering growth. But mutations that make YFP misfold abrogate Fcy1 toxicity, thus strains possessing misfolded YFP variants rise to high frequency in growth competition experiments. This makes such strains easier to study. The Intra-FCY1 system cancels localization of the protein of interest, thus can be applied to study the relative stability of mutant versions of diverse cellular proteins. Here, we confirm this method can identify novel mutations that cause misfolding, highlighting the potential for Intra-FCY1 to illuminate the relationship between protein sequence and stability.
Insights into the physiological, molecular, and genetic regulators of albinism in Camellia sinensis leaves
Authors: Zhao Yang , Yang Peidi , Cheng Yang , Liu Yong , Yang Yang , Liu Zhen
Published: September 2023

Introduction: Yanling Yinbiancha, a cultivar of Camellia sinensis (L.) O. Kuntze, is an evergreen woody perennial with characteristic albino leaves. A mutant variant with green leaves on branches has been recently identified. The molecular mechanisms underlying this color variation remain unknown.

Methods: We aimed to utilize omics tools to decipher the molecular basis for this color variation, with the ultimate goal of enhancing existing germplasm and utilizing it in future breeding programs.

Results and discussion: Albinotic leaves exhibited significant chloroplast degeneration and reduced carotenoid accumulation. Transcriptomic and metabolomic analysis of the two variants revealed 1,412 differentially expressed genes and 127 differentially accumulated metabolites (DAMs). Enrichment analysis for DEGs suggested significant enrichment of pathways involved in the biosynthesis of anthocyanins, porphyrin, chlorophyll, and carotenoids. To further narrow down the causal variation for albinotic leaves, we performed a conjoint analysis of metabolome and transcriptome and identified putative candidate genes responsible for albinism in C. sinensis leaves. 12, 7, and 28 DEGs were significantly associated with photosynthesis, porphyrin/chlorophyll metabolism, and flavonoid metabolism, respectively. Chlorophyllase 2, Chlorophyll a-Binding Protein 4A, Chlorophyll a-Binding Protein 24, Stay Green Regulator, Photosystem II Cytochrome b559 subunit beta along with transcription factors AP2, bZIP, MYB, and WRKY were identified as a potential regulator of albinism in Yanling Yinbiancha. Moreover, we identified Anthocyanidin reductase and Arabidopsis Response Regulator 1 as DEGs influencing flavonoid accumulation in albino leaves. Identification of genes related to albinism in C. sinensis may facilitate genetic modification or development of molecular markers, potentially enhancing cultivation efficiency and expanding the germplasm for utilization in breeding programs.
Raising awareness of sex and gender bias in artificial intelligence and health
Authors: Buslón Nataly , Cortés Atia , Catuara-Solarz Silvina , Cirillo Davide , Rementeria Maria José
Published: September 2023

Historically, biomedical research has been led by and focused on men. The recent introduction of Artificial Intelligence (AI) in this area has further proven this practice to be discriminatory for other sexes and genders, more noticeably for women. To move towards a fair AI development, it is essential to include sex and gender diversity both in research practices and in the workplace. In this context, the Bioinfo4women (B4W) program of the Barcelona Supercomputing Center (i) promotes the participation of women scientists by improving their visibility, (ii) fosters international collaborations between institutions and programs and (iii) advances research on sex and gender bias in AI and health. In this article, we discuss methodology and results of a series of conferences, titled â€œSex and Gender Bias in Artificial Intelligence and Health, organized by B4W and La Caixa Foundation from March to June 2021 in Barcelona, Spain. The series consisted of nine hybrid events, composed of keynote sessions and seminars open to the general audience, and two working groups with invited experts from different professional backgrounds (academic fields such as biology, engineering, and sociology, as well as NGOs, journalists, lawyers, policymakers, industry). Based on this awareness-raising action, we distilled key recommendations to facilitate the inclusion of sex and gender perspective into public policies, educational programs, industry, and biomedical research, among other sectors, and help overcome sex and gender biases in AI and health.
Use of high-plex data provides novel insights into the temporal artery processes of giant cell arteritis
Authors: Parreau Simon , Molina Elsa , Dumonteil Stéphanie , Goulabchand Radjiv , Naves Thomas , Bois Melanie C. , Akil Hussein , Terro Faraj , Fauchais Anne-Laure , Liozon Eric , Jauberteau Marie-Odile , Weyand Cornelia M. , Ly Kim-Heang
Published: September 2023

Objective

To identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed an in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls. Furthermore, we performed pharmacogenomic network analysis to identify potential treatment targets.

Methods

Using human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA, n = 9; controls, n = 7), we performed a whole transcriptome analysis using the NanoString GeoMx Digital Spatial Profiler. In total, 59 regions of interest were selected in the intima, media, adventitia, and perivascular adipose tissue (PVAT). Differentially expressed genes (DEGs) (fold-change > 2 or < −2, p-adjusted < 0.01) were compared across each layer to build a spatial and pharmacogenomic network and to explore the pathophysiological mechanisms of GCA.

Results

Most of the transcriptome (12,076 genes) was upregulated in GCA arteries, compared to control arteries. Among the screened genes, 282, 227, 40, and 5 DEGs were identified in the intima, media, adventitia, and PVAT, respectively. Genes involved in the immune process and vascular remodeling were upregulated within GCA temporal arteries but differed across the arterial layers. The immune-related functions and vascular remodeling were limited to the intima and media.

Conclusion

This study is the first to perform an in situ spatial profiling characterization of the molecules involved in GCA. The pharmacogenomic network analysis identified potential target genes for approved and novel immunotherapies.
Immune reconstitution following alemtuzumab therapy is characterized by exhausted T cells, increased regulatory control of proinflammatory T cells and reduced B cell control
Authors: von Essen Marina Rode , Chow Helene Højsgaard , Holm Hansen Rikke , Buhelt Sophie , Sellebjerg Finn
Published: September 2023

Alemtuzumab is a monoclonal antibody targeting CD52 on the surface of immune cells, approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS). The purpose of this study was to analyze the repopulation of peripheral lymphocytes following alemtuzumab-induced lymphocyte depletion and investigate associations with disease activity and development of secondary autoimmunity. For this, blood samples were collected two years after initiation of alemtuzumab treatment and lymphocytes were subjected to a comprehensive flow cytometry analysis. Included in the study were 40 patients treated with alemtuzumab and 40 treatment-naïve patients with RRMS. Disease activity and development of secondary autoimmune disease was evaluated after three years of treatment. Our study confirms that alemtuzumab treatment profoundly alters the circulating lymphocyte phenotype and describes a reconstituted immune system characterized by T cell activation/exhaustion, an increased regulatory control of IL-17 producing effector T cells and CD20+ T cells, and a reduced control of B cells. There were no obvious associations between immune cell subsets and disease activity or development of secondary autoimmune disease during treatment with alemtuzumab. Our results indicate that the reconstituted immune response is skewed towards a more effective regulatory control of MS-associated proinflammatory T cell responses. Also, the enlarged pool of naïve B cells together with the apparent decrease in control of B cell activity may explain why alemtuzumab-treated patients retain the ability to mount a humoral immune response towards new antigens.
A role of inflammaging in aortic aneurysm: new insights from bioinformatics analysis
Authors: Wang Shilin , Liu Hao , Yang Peiwen , Wang Zhiwen , Ye Ping , Xia Jiahong , Chen Shu
Published: September 2023

Introduction

Aortic aneurysms (AA) are prevalent worldwide with a notable absence of drug therapies. Thus, identifying potential drug targets is of utmost importance. AA often presents in the elderly, coupled with consistently raised serum inflammatory markers. Given that ageing and inflammation are pivotal processes linked to the evolution of AA, we have identified key genes involved in the inflammaging process of AA development through various bioinformatics methods, thereby providing potential molecular targets for further investigation.

Methods

The transcriptome data of AA was procured from the datasets GSE140947, GSE7084, and GSE47472, sourced from the NCBI GEO database, whilst gene data of ageing and inflammation were obtained from the GeneCards Database. To identify key genes, differentially expressed analysis using the “Limma” package and WGCNA were implemented. Protein-protein intersection (PPI) analysis and machine learning (ML) algorithms were employed for the screening of potential biomarkers, followed by an assessment of the diagnostic value. Following the acquisition of the hub inflammaging and AA-related differentially expressed genes (IADEGs), the TFs-mRNAs-miRNAs regulatory network was established. The CIBERSORT algorithm was utilized to investigate immune cell infiltration in AA. The correlation of hub IADEGs with infiltrating immunocytes was also evaluated. Lastly, wet laboratory experiments were carried out to confirm the expression of hub IADEGs.

Results

342 and 715 AA-related DEGs (ADEGs) recognized from GSE140947 and GSE7084 datasets were procured by intersecting the results of “Limma” and WGCNA analyses. After 83 IADEGs were obtained, PPI analysis and ML algorithms pinpointed 7 and 5 hub IADEGs candidates respectively, and 6 of them demonstrated a high diagnostic value. Immune cell infiltration outcomes unveiled immune dysregulation in AA. In the wet laboratory experiments, 3 hub IADEGs, including BLNK, HLA-DRA, and HLA-DQB1, finally exhibited an expression trend in line with the bioinformatics analysis result.

Discussion

Our research identified three genes - BLNK, HLA-DRA, and HLA-DQB1- that play a significant role in promoting the development of AA through inflammaging, providing novel insights into the future understanding and therapeutic intervention of AA.
Biological carbon pump responses to multiscale physical processes: a review of sediment trap studies in the South China Sea
Authors: Zhang Jingjing , Li Hongliang , Wiesner Martin G. , Ran Lihua , He Xingju , Chi Guangxi , Wang Xinyang , Yu Jinping , Chen Jianfang
Published: September 2023

Accurately assessing the capacity of the modern ocean to photosynthetically fix and sequester atmospheric CO2, termed the biological carbon pump (BCP), is a key component in studies on the marine carbon cycle and the global climate system. Particulate organic carbon (POC) flux into the ocean interior is an important indicator of the BCP strength, and it can be directly measured by sediment traps on time scales from days to years. This study has been conducted in the South China Sea (SCS) for over three decades. The SCS is one of the largest tropical marginal seas, located in the Asian monsoon region with frequent occurrence of dynamic physical processes and anthropogenic perturbations. It hosts an ideal natural laboratory to investigate the response of the BCP to multiscale physical processes. In this mini review, we briefly introduce the study history of mooring sediment traps in the SCS, synthesize the processes that regulate the temporal variability in mesopelagic POC flux, and how it is sensitive to climate changes. The time-series characteristics of the POC flux are clearly linked to primary production, as well as the key physical processes in the upper layer. The seasonal East Asian monsoon, intraseasonal eddies, aerosol deposition and interannual El Niño Southern Oscillation (ENSO) events are the main controlling factors over weekly to yearly timescales. Together, they suggest that the multiscale physical forcing in the upper layer regulates the mesopelagic POC export flux by controlling nutrient supplementation and subsequent POC production.
Investigation of the individual genetic evolution of SARS-CoV-2 in a small cluster during the rapid spread of the BF.5 lineage in Tokyo, Japan
Authors: Jin Bo , Oyama Rieko , Tabe Yoko , Tsuchiya Koji , Hando Tetsuya , Wakita Mitsuru , Yan Yan , Saita Mizue , Takei Satomi , Horiuchi Yuki , Miida Takashi , Naito Toshio , Takahashi Kazuhisa , Ogawa Hideoki
Published: September 2023

There has been a decreasing trend in new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases and fatalities worldwide. The virus has been evolving, indicating the potential emergence of new variants and uncertainties. These challenges necessitate continued efforts in disease control and mitigation strategies. We investigated a small cluster of SARS-CoV-2 Omicron variant infections containing a common set of genomic mutations, which provided a valuable model for investigating the transmission mechanism of genetic alterations. We conducted a study at a medical center in Japan during the Omicron surge (sub-lineage BA.5), sequencing the entire SARS-CoV-2 genomes from infected individuals and evaluating the phylogenetic tree and haplotype network among the variants. We compared the mutations present in each strain within the BA.5 strain, TKYnat2317, which was first identified in Tokyo, Japan. From June 29th to July 4th 2022, nine healthcare workers (HCWs) tested positive for SARS-CoV-2 by real-time PCR. During the same period, five patients also tested positive by real-time PCR. Whole genome sequencing revealed that the infected patients belonged to either the isolated BA.2 or BA.5 sub-lineage, while the healthcare worker infections were classified as BF.5. The phylogenetic tree and haplotype network clearly showed the specificity and similarity of the HCW cluster. We identified 12 common mutations in the cluster, including I110V in nonstructural protein 4 (nsp4), A1020S in the Spike protein, and H47Y in ORF7a, compared to the BA.5 reference. Additionally, one case had the extra nucleotide-deletion mutation I27* in ORF10, and low frequencies of genetic alterations were also found in certain instances. The results of genome sequencing showed that the nine HCWs shared a set of genetic mutations, indicating transmission within the cluster. Minor mutations observed in five HCW individuals suggested the emergence of new virus variants. Five amino acid substitutions occurred in nsp3, which could potentially affect virus replication or immune escape. Intra-host evolution also generated additional mutations. The cluster exhibited a mild disease course, with individuals in this case, recovering without requiring any medical treatments. Further investigation is needed to understand the relationship between the genetic evolution of the virus and the symptoms.
Impact of clozapine monotherapy on gut microbiota and metabolism in people with schizophrenia
Authors: Yin Feiyan , Shi Zhidao , Ma Xiquan , Ding Kai , Zhang Yuan , Ma Sha
Published: September 2023

Background

Clozapine is considered one of the most effective antipsychotic drugs, but it is most likely to cause metabolic abnormalities. Researchers have studied the causes of metabolic abnormalities caused by clozapine from multiple perspectives, but the reasons remain unclear.

Purpose

Characterize the gut microbiota of people with schizophrenia taking clozapine, exploring the association between gut microbiota and glucose lipid metabolic markers in schizophrenia patients taking clozapine.

Research design

Sixty-one long-term inpatients with schizophrenia in clozapine monotherapy were selected as study subjects. We got four subgroups by sex and the presence of metabolic syndrome.

Data analysis

16s analysis technology was applied at the genus level to determine the classification of gut microbiota. Then we compared the characteristics of gut microbiota and the association of gut microbiota with glucose lipid metabolic markers in each group.

Findings

We found differences in the diversity of gut microbiota among groups. The association between gut microbiota and glucose lipid metabolic markers was complicated. Gender was an important differentiating factor. Oscillibacter has a low abundance. However, it was the only genus associated with glycemic or lipids in each group. Among metabolic syndromes, Gemmiger was positively correlated with most lipids in females but negatively correlated in males, showing gender differences. In female non-metabolic syndromes, Bifidobacterium lost its probiotic character; instead, showing pathogenicity, which has strong positive correlations with fasting blood glucose and low-density lipoprotein but negative correlations with Apolipoprotein A1. Maybe schizophrenia, taking clozapine, and gender factors influenced the gut microbiota, which complicated our findings. The significance of the results remains to be determined by in-depth studies.
Switching to second line MS disease-modifying therapies is associated with decreased relapse rate
Authors: Marriott James John , Ekuma Okechukwu , Fransoo Randall , Marrie Ruth Ann
Published: September 2023

Background and objectives

While randomized, controlled trials (RCTs) are the gold standard for determining treatment efficacy, they do not capture the effectiveness of treatment during real-world use. We aimed to evaluate the association between demographics and multiple sclerosis (MS) disease-modifying therapy (DMT) exposure, including treatment adherence and switches between different DMTs, on the risk of subsequent MS relapse.

Methods

All persons with relapsing-onset MS (pwRMS) living in Manitoba between 1999 and 2014 were identified from provincial healthcare databases using a validated case definition. Use of DMTs was abstracted from the provincial drug database covering all residents of Manitoba, including use of any DMT, stopping/starting any DMT, switches between different DMTs and adherence as defined by cumulative medication possession ratios (CUMMPRs) of 50, 70, 80 and 90%. Time to first-treated relapse was used as the outcome of interest in logistic regression and Cox-proportional hazards regression models adjusting for demographic covariates including age and year of diagnosis, sex, socioeconomic status and number of medical comorbidities.

Results

1780 pwRMS were identified, including 1,510 who were on DMT at some point in the study period. While total DMT exposure was not associated with the time to subsequent treated relapse, individuals who switched between more than 2 DMTs had higher post-switch rates of relapse. Switching to second-line DMTs was associated with a longer time to treated relapse in comparison to those who remained on a first-line DMT (HR 0.44; 95%CI: 0.32–0.62, p < 0.0001).

Discussion

Switching to high-efficacy DMTs reduces the rates of subsequent MS relapse at the population level.
Pediatric traumatic brain injuries in war zones: a systematic literature review
Authors: Aguirre Alex S. , Rojas Kenny , Torres Alcy R.
Published: September 2023

Background

Pediatric casualties in war zones are a devastating consequence of armed conflicts, causing significant challenges for affected children, especially in the context of poor access to care. This study aimed to understand traumatic brain injuries (TBIs) in this high-risk population and to identify and provide information for the stakeholders, as well as to recognize severe long-term consequences and develop strategies to prevent them, thus minimizing their burden while aiding in the management of these cases.

Methods

We carried out a systematic literature review following PRISMA guidelines to identify publications discussing traumatic brain injuries in children in the context of war zones, and we analyzed all the collected data.

Results

Our study showed that head injuries were the most common casualty in war zones; male and female children were affected, and the mean age was 8–10 years. Most children were reported to be from Afghanistan, and blasts were the most common mechanism of injury. The mortality fluctuated from 3 to 47%.

Conclusion

There is a lack of evidence-based information regarding the characterization, approach, and management of children with TBI in conflict zones. While the world finds ways to live in peace, there is an urgency to research, train, and deploy enough specialists to these areas, if governments are serious about improving outcomes for this population.
Synaptic activity is not required for establishing heterogeneity of inner hair cell ribbon synapses
Authors: Karagulyan Nare , Moser Tobias
Published: September 2023

Neural sound encoding in the mammalian cochlea faces the challenge of representing audible sound pressures that vary over six orders of magnitude. The cochlea meets this demand through the use of active micromechanics as well as the diversity and adaptation of afferent neurons and their synapses. Mechanisms underlying neural diversity likely include heterogeneous presynaptic input from inner hair cells (IHCs) to spiral ganglion neurons (SGNs) as well as differences in the molecular profile of SGNs and in their efferent control. Here, we tested whether glutamate release from IHCs, previously found to be critical for maintaining different molecular SGN profiles, is required for establishing heterogeneity of active zones (AZs) in IHCs. We analyzed structural and functional heterogeneity of IHC AZs in mouse mutants with disrupted glutamate release from IHCs due to lack of a vesicular glutamate transporter (Vglut3) or impaired exocytosis due to defective otoferlin. We found the variance of the voltage-dependence of presynaptic Ca2+ influx to be reduced in exocytosis-deficient IHCs of otoferlin mutants. Yet, the spatial gradients of maximal amplitude and voltage-dependence of Ca2+ influx along the pillar-modiolar IHC axis were maintained in both mutants. Further immunohistochemical analysis showed an intact spatial gradient of ribbon size in Vglut3–/– mice. These results indicate that IHC exocytosis and glutamate release are not strictly required for establishing the heterogeneity of IHC AZs.
Cyclophosphamide augments the efficacy of in situ vaccination in a mouse melanoma model
Authors: Tsarovsky Noah , Felder Mildred , Heck Mackenzie , Slowinski Jacob , Rasmussen Kayla , VandenHeuvel Sabrina , Zaborek Jen , Morris Zachary S. , Erbe Amy K. , Sondel Paul M. , Rakhmilevich Alexander L.
Published: September 2023

Introduction

We have previously shown that an intratumoral (IT) injection of the hu14.18-IL2 immunocytokine (IC), an anti-GD2 antibody linked to interleukin 2, can serve as an in situ vaccine and synergize with local radiotherapy (RT) to induce T cell-mediated antitumor effects. We hypothesized that cyclophosphamide (CY), a chemotherapeutic agent capable of depleting T regulatory cells (Tregs), would augment in situ vaccination. GD2+ B78 mouse melanoma cells were injected intradermally in syngeneic C57BL/6 mice.

Methods

Treatments with RT (12Gy) and/or CY (100 mg/kg i.p.) started when tumors reached 100-300 mm3 (day 0 of treatment), followed by five daily injections of IT-IC (25 mcg) on days 5-9. Tumor growth and survival were followed. In addition, tumors were analyzed by flow cytometry.

Results

Similar to RT, CY enhanced the antitumor effect of IC. The strongest antitumor effect was achieved when CY, RT and IC were combined, as compared to combinations of IC+RT or IC+CY. Flow cytometric analyses showed that the combined treatment with CY, RT and IC decreased Tregs and increased the ratio of CD8+ cells/Tregs within the tumors. Moreover, in mice bearing two separate tumors, the combination of RT and IT-IC delivered to one tumor, together with systemic CY, led to a systemic antitumor effect detected as shrinkage of the tumor not treated directly with RT and IT-IC. Cured mice developed immunological memory as they were able to reject B78 tumor rechallenge.

Conclusion

Taken together, these preclinical results show that CY can augment the antitumor efficacy of IT- IC, given alone or in combination with local RT, suggesting potential benefit in clinical testing of these combinations.
Risk factors for lateral pelvic lymph node metastasis in patients with lower rectal cancer: a systematic review and meta-analysis
Authors: Zeng De-xing , Yang Zhou , Tan Ling , Ran Meng-ni , Liu Zi-lin , Xiao Jiang-wei
Published: September 2023

Background and objective

Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence (LR) in patients with rectal cancer (RC). The evaluation criteria of lateral lymph node dissection (LLND) for patients in eastern (mainly in Japan) and western countries have been controversial. The aim of this study was to analyse the risk factors for LPLN metastasis in order to guide surgical methods.

Methods

We searched relevant databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 05 October 2022 to evaluate the risk factors for LPLN metastasis in patients with RC in this meta-analysis.

Results

A total of 24 articles with 5843 patients were included in this study. The overall results showed that female sex, age <60 years, pretherapeutic CEA level >5 ng/ml, clinical T4 stage (cT4), clinical M1 stage (cM1), distance of the tumour from the anal verge (AV) <50 mm, tumour centre located below the peritoneal reflection (Rb), short axis (SA) of LPLN ≥8 mm before nCRT, short axis (SA) of LPLN ≥5 mm after nCRT, border irregularity of LPLN, tumour size ≥50 mm, pathological T3-4 stage (pT3-4), pathological N2 stage (pN2), mesorectal lymph node metastasis (MLNM), lymphatic invasion (LI), venous invasion (VI), CRM (+) and poor differentiation were significant risk factors for LPLN metastasis (P <0.05).

Conclusion

This study summarized almost all potential risk factors of LPLN metastasis and expected to provide effective treatment strategies for patients with LRC. According to the risk factors of lateral lymph node metastasis, we can adopt different comprehensive treatment strategies. High-risk patients can perform lateral lymph node dissection to effectively reduce local recurrence; In low-risk patients, we can avoid overtreatment, reduce complications and trauma caused by lateral lymph node dissection, and maximize patient survival and quality of life.