bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gut microbiota correlate with the disease characteristics and immune status of patients with untreated diffuse large B-cell lymphoma
Authors: Lin Zhouning , Mao Dan , Jin Changyu , Wang Jiaping , Lai Yanli , Zhang Yanli , Zhou Miao , Ge Qunfang , Zhang Ping , Sun Yongcheng , Xu Kaihong , Wang Yi , Zhu Huiling , Lai Binbin , Wu Hao , Mu Qitian , Ouyang Guifang , Sheng Lixia 
Published: February 2023

BackgroundGut microbiota characteristics in patients with diffuse large B-cell lymphoma (DLBCL) are reportedly different when compared with the healthy population and it remains unclear if the gut microbiota affects host immunity and clinical disease features. This research investigated the gut microbiota in patients with untreated DLBCL and analyzed its correlation with patient clinical characteristics, humoral, and cell immune status.MethodsThirty-five patients with untreated DLBCL and 20 healthy controls (HCs) were recruited to this study and microbiota differences in stool samples were analyzed by 16S rDNA sequencing. Absolute ratios of immune cell subset counts in peripheral blood were detected by flow cytometry and peripheral blood cytokine levels were detected by enzyme-linked immunosorbent assay. Relationships between changes in patient microbiomes and clinical characteristics, such as clinical stage, international prognostic index (IPI) risk stratification, cell origin, organ involved and treatment responses were investigated and correlations between differential microbiota and host immune indices were analyzed.ResultsThe alpha-diversity index of intestinal microecology in DLBCL patients was not significantly different when compared with HCs (P&gt;0.05), nonetheless beta-diversity was significantly decreased (P=0.001). p_Proteobacteria were dominant in DLBCL, while p_Bacteroidetes abundance was significantly decreased when compared with HCs (P&lt;0.05). Gut microbiota characteristics were identified that were associated with clinical features, such as tumor load, risk stratification and cell origin, and correlation analyses were performed between differential flora abundance associated with these clinical features and host immune status. The p_Firmicutes was positively correlated with absolute lymphocyte values, g_Prevotella_2 and s_un_g_Prevotella_2 were negatively correlated with absolute lymphocyte values, T cell counts and CD4 cell counts, while g_Pyramidobacter, s_un_g_Pyramidobacter, and f_Peptostreptococcaceae were negatively correlated with IgA.ConclusionsDominant gut microbiota, abundance, diversity, and structure in DLBCL were influenced by the disease, correlated with patient immune status and this suggested that the microecology-immune axis may be involved in regulating lymphoma development. In the future, it may be possible to improve immune function in patients with DLBCL by regulating the gut microbiota, improve treatment response rates and increase patient survival rates.
Bio-deposition approaches for sustainable execution of recycled aggregates in concretes
Authors: Ahmad Muhammad Arslan , Liu Bing , Li Qiuwei , Adeel Muhammad , Zhang Jinlong , Zhou Yingwu , Deng Xu 
Published: February 2023

Our study offers a quantitative framework for microbial-induced calcium carbonate precipitation (MICP) to uplift the properties of recycled aggregate concrete (RAC). In this regard, a marine alkalophilic bacterium Bacillus sp. B6 was employed, and its growth and mineralization efficiency under seawater conditions was investigated. Optimization of MICP was achieved with different nutrient sources and bacterial introduction methods (dip and spray). The efficiency of treated recycled aggregates (RA) was determined by using scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) in combination with basic technologies of density improvement and water absorption. The results show that the optimal nutrient sources of carbon and nitrogen are glucose (7 g L−1) and tryptone (5 gL−1), respectively. Spray treated recycled aggregate (RA) is reported to be efficient with a reduction in water absorption (∼19%), and improvement in bulk (∼2.4%) and apparent density (∼1.7%). The effectiveness of the MICP treatment process is confirmed with SEM and EDX observations, indicating the filling of microcracks with calcium carbonates. As such, the mechanical properties of RAC with spray treated RA significantly increase by up to ∼24% in compressive strength as compared to the control treatment. Current findings will help revitalize the construction industry by utilizing the MICP-treated RA and minimizing the load on natural aggregates.
Access and reimbursement pathways for digital health solutions and in vitro diagnostic devices: Current scenario and challenges
Authors: Mantovani Andrea , Leopaldi Claudia , Nighswander Cassandra Maria , Di Bidino Rossella 
Published: February 2023

ObjectivesDigital therapeutics (DTx) are innovative solutions that use meaningful data to provide evidence-based decisions for the prevention, treatment, and management of diseases. Particular attention is paid to software-based in vitro diagnostics (IVDs). With this point of view, a strong connection between DTx and IVDs is observed.MethodsWe investigated the current regulatory scenarios and reimbursement approaches adopted for DTx and IVDs. The initial assumption was that countries apply different regulations for the access to the market and adopt different reimbursement systems for both DTx and IVDs. The analysis was limited to the US, European countries (Germany, France, and UK), and Australia due to maturity in digital health product adoption and regulatory processes, and recent regulations related to IVDs. The final aim was to provide a general comparative overview and identify those aspects that should be better addressed to support the adoption and commercialization of DTx and IVDs.ResultsMany countries regulate DTx as medical devices or software integrated with a medical device, and some have a more specific pathway than others. Australia has more specific regulations classifying software used in IVD. Some EU countries are adopting similar processes to the Digital Health Applications (DiGA) under Germany's Digitale-Versorgung Gesetz (DVG) law, which deems DTx eligible for reimbursement during the fast access pathway. France is working on a fast-track system to make DTx available to patients and reimbursable by the public system. The US retains some coverage through private insurance, federal and state programs like Medicaid and Veterans Affairs, and out-of-pocket spending. The updated Medical Devices Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) in the EU includes a classification system specifying how software integrated with medical devices, and IVDs specifically must be regulated.ConclusionThe outlook for DTx and IVDs is changing as they are becoming more technologically advanced, and some countries are adapting their device classifications depending on specific features. Our analysis showed the complexity of the issue demonstrating how fragmented are regulatory systems for DTx and IVDs. Differences emerged in terms of definitions, terminology, requested evidence, payment approaches and the overall reimbursement landscape. The complexity is expected to have a direct impact on the commercialization of and access to DTx and IVDs. In this scenario, willingness to pay of different stakeholders is a key theme.
Thermostability modification of β-mannanase from Aspergillus niger via flexibility modification engineering
Authors: Tan Shundong , Tao Xiumei , Zheng Pu , Chen Pengcheng , Yu Xiaowei , Li Ning , Gao Tiecheng , Wu Dan 
Published: February 2023

Introductionβ-Mannanases can hydrolyze mannans, which are widely available in nature. However, the optimum temperature of most β-mannanases is too low to be directly utilized in industry.MethodsTo further improve the thermostability of Anman (mannanase from Aspergillus niger CBS513.88), B-factor and Gibbs unfolding free energy change were used to modify the flexible of Anman, and then combined with multiple sequence alignment and consensus mutation to generate an excellent mutant. At last, we analyzed the intermolecular forces between Anman and the mutant by molecular dynamics simulation.ResultsThe thermostability of combined mutant mut5 (E15C/S65P/A84P/A195P/T298P) was increased by 70% than the wild-type Amman at 70°C, and the melting temperature (Tm) and half-life (t1/2) values were increased by 2°C and 7.8-folds, respectively. Molecular dynamics simulation showed reduced flexibility and additional chemical bonds in the region near the mutation site.DiscussionThese results indicate that we obtained a Anman mutant that is more suitable for industrial application, and they also confirm that a combination of rational and semi-rational techniques is helpful for screening mutant sites.
Effects of Aspergillus niger on cyanogenic glycosides removal and fermentation qualities of ratooning sorghum
Authors: Zhai Jianrong , Wang Bo , Sun Yingpeng , Yang Jianfeng , Zhou Junfeng , Wang Tianyu , Zhang Wenlan , Qi Cai , Guo Yanjun 
Published: February 2023

IntroductionCyanogenic glycosides (CNglcs) are bioactive plant products involving in plant defense against herbivores by virtue of their abilities to release toxic hydrogen cyanide (HCN). Aspergillus niger has been shown to be effective in producing β-glucosidase, which could degrade CNglcs. However, whether A. niger could remove CNglcs under ensiling conditions is still unknown.MethodsIn this study, we first investigated the HCN contents in ratooning sorghums for two years, then the sorghums were ensiled with or without the addition of A. niger.ResultsTwo years’ investigation indicated that the contents of HCN in fresh ratooning sorghum were larger than 801 mg/kg FW (fresh weight), which could not be reduced by silage fermentation under safety threshold (200 mg/kg FW). A. niger could produce β-glucosidase over a range of pH and temperature, which degraded the CNglcs and removed the hydrogen cyanide (HCN) at early days of ratooning sorghum fermentation. The addition of A. niger (2.56 × 107 CFU/ml) altered the microbial community, increased bacterial diversity, improved the nutritive qualities, and reduced the HCN contents in ensiled ratooning sorghum lower than 100 mg/kg FW after 60 days of fermentation. Overall, the addition of 150 ml A. niger + 50 ml sterile water per 3 kg silage could efficiently remove CNglcs from ratooning sorghum silage.ConclusionIn conclusion, A. niger could produce β-glucosidase which degraded the CNglcs during the early days of fermentation, benefiting the ensiling process and improving the utilization of ratooning sorghum.
Metabolome combined with gut microbiome revealed the lipid-lowering mechanism of Xuezhiping capsule on hyperlipidemic hamster induced by high fat diet
Authors: Wang Li , Zhang Zhixin , Luo Gan , Wang Ying , Du Ke , Gao Xiaoyan 
Published: February 2023

Introduction: Hyperlipidemia is a common metabolic disorder with presence of excess fat or lipids in the blood, may induce liver injury, oxidative stress and inflammatory. Xuezhiping capsule (XZP) is a famous Chinese patent medicine clinically used for anti-hyperlipidemia. However, the regulation mechanism of XZP on hyperlipidemia has not been elucidated so far.Methods: This study aimed to explore the effects of XZP on hypolipidemic, antioxidant and anti-inflammatory effects, and the potential mechanism by a combination of untargeted metabolomics and 16S rRNA sequencing.Results: The results indicated that XZP reduced the level of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), increased the level of high density liptein cholesterol (HDL-C), alleviated excessive accumulation of lipid droplets in liver. Biochemical indexes of liver function including gamma glutamyl transferase (GGT) and glutamic oxaloacetic transaminase (GOT) in liver were remarkably decreased. Meanwhile, XZP increased the level of oxidative stress biochemical indexes including superoxide dismutase (SOD) and glutathione (GSH). In addition, XZP increased the level of peroxisome proliferators-activated receptors α (PPARα), acetyl CoA carboxylase 1 (ACOX1) and cholesterol 7-alpha hydroxylase (CYP7A1) in liver, and improved lipid metabolism in serum, liver and fecal lipid metabolism. XZP increased diversity index and the ratio of Firmicutes and Bacteroidetes, regulated seventeen genera, and illustrated strong correlations with liver lipid metabolism and phenotypic indicators.Discussion: These findings suggest that XZP reduced blood lipid and liver lipid, protected liver function, anti inflammation and anti-oxidation, ameliorate lipid metabolic disorders by modulating alpha linolenic acid and linoleic acid metabolism, bile acid metabolism, arachidonic acid metabolism, and regulated gut microbiota composition of high-fat diet (HFD) hamsters.
Predictors of cognitive and physical decline: Results from the Health Aging and Body Composition Study
Authors: Handing Elizabeth P. , Hayden Kathleen M. , Leng Xiaoyan Iris , Kritchevsky Stephen B. 
Published: February 2023

BackgroundRisk factors for cognitive decline and physical decline have been studied independently, however older adults might experience decline in both areas i.e., dual decline. Risk factors associated with dual decline are largely unknown and have significant implications on health outcomes. The aim of this study is to explore risk factors associated with dual decline.MethodsUsing data from the Health, Aging and Body Composition (Health ABC) study, a longitudinal prospective cohort study, we examined trajectories of decline based on repeated measures of the Modified Mini-Mental State Exam (3MSE) and the Short Physical Performance Battery (SPPB) across 6 years (n=1,552). We calculated four mutually exclusive trajectories of decline and explored predictors of decline: cognitive decline (n = 306) = lowest quartile of slope on the 3MSE or 1.5 SD below mean at baseline, physical decline (n = 231) = lowest quartile of slope on the SPPB or 1.5 SD below mean at baseline, dual decline (n = 110) = lowest quartile in both measures or 1.5 SD below mean in both measures at baseline. Individuals who did not meet criteria for one of the decline groups were classified as the reference group. (n= 905).ResultsMultinomial logistic regression tested the association of 17 baseline risk factors with decline. Odds of dual decline where significantly higher for individuals at baseline with depressive symptoms (CES-D &gt;16) (Odds Ratio (OR)=2.49, 95% Confidence Interval (CI): 1.05-6.29), ApoE-ε4 carrier (OR= 2.09, 95% CI: 1.06-1.95), or if individuals had lost 5+lbs in past year (OR=1.79, 95% CI: 1.13-2.84). Odds were significantly lower for individuals with a higher score on the Digit Symbol Substitution Test per standard deviation (OR per SD: 0.47, 95% CI 0.36-0.62) and faster 400-meter gait (OR per SD= 0.49, 95% CI: 0.37-0.64).ConclusionAmong predictors, depressive symptoms at baseline significantly increased the odds of developing dual decline but was not associated with decline in the exclusively cognitive or physical decline groups. APOE-ε4 status increased the odds for cognitive decline and dual decline but not physical decline. More research on dual decline is needed because this group represents a high risk, vulnerable subset of older adults.
Selection of patients with acute vertebrobasilar artery occlusion for endovascular treatment by magnetic resonance imaging
Authors: Chen Jun , Zhang Jiwei , Zhu Xianjin , Zhang Xuebin , Jiang Bin , Liu Qi , Wei Zheng Z. 
Published: February 2023

Background and purposeThe best method for selecting patients with acute vertebrobasilar artery occlusion (VBAO) who would benefit from endovascular treatment (EVT) is still the key question. This study aimed to assess the efficacy of magnetic resonance imaging (MRI) for selecting patients with acute VBAO for EVT.Materials and methodsA total of 14 patients with suspected acute VBAO on MR angiography (MRA) in the EVT database (from April 2016 to August 2019) were enrolled. Acute Stroke Prognosis Early Computed Tomography Score (ASPECTS) and pons–midbrain index were assessed on diffusion-weighted imaging (DWI). EVT included a stent retriever and a rescue treatment (angioplasty and/or stenting). The proportion of successful reperfusion and favorable functional outcomes (modified Rankin Scale ≤ 3) at 90 days was documented.ResultsA total of 11 patients were included in the final analysis. The median DWI-ASPECTS and pons–midbrain index were 7 and 2, respectively. Underlying stenosis was detected in 10 of 11 (90.9%) patients. Balloon angioplasty and/or stenting were used as rescue therapy for five patients and two patients, respectively. A total of nine patients (81.8%) achieved successful reperfusion (mTICI, 2b, or 3). The 90-day mRS score of 0–3 was achieved in six (54.5%) patients. The mortality rate within 90 days was 18.2% (two of 11 patients).ConclusionDWI plus MRA could help select the patients with acute VBAO for EVT by assessing ASPECTS and the pons–midbrain index. Patients could achieve good reperfusion and favorable functional outcomes.
A homozygous PRKN-associated juvenile Parkinson's disease with pregnancy in China
Authors: Li Hong-xing , Dong Mei , Peng Xiao-xiao , Liu Yi-zhe , Wang Han , Li Chao , Du Yi-yi , Zhang Kai , Zong Qiang 
Published: February 2023

BackgroundAlthough Parkinson's disease (PD) is the second most common neurodegenerative disorder, pregnancy in patients with PD is a relatively rare occurrence because the most common age of onset of PD is beyond the childbearing age, except in patients with Young-Onset PD (YOPD) caused by parkin RBR E3 ubiquitin protein ligase (PRKN) mutations.CaseIn this study, we report the case of a 30-year-old Chinese woman who was affected by PRKN-associated YOPD and was treated with levodopa/benserazide during pregnancy. She gave birth to a healthy baby boy with an Apgar score of 9 through an uncomplicated vaginal delivery.ConclusionThis case further suggests that levodopa/benserazide during pregnancy is safe in the treatment of PRKN-associated YOPD.
DSC MRI in the human brain using deoxyhemoglobin and gadolinium—Simulations and validations at 3T
Authors: Schulman Jacob Benjamin , Sayin Ece Su , Manalac Angelica , Poublanc Julien , Sobczyk Olivia , Duffin James , Fisher Joseph A. , Mikulis David , Uludağ Kâmil 
Published: February 2023

IntroductionDynamic susceptibility contrast (DSC) MRI allows clinicians to determine perfusion parameters in the brain, such as cerebral blood flow, cerebral blood volume, and mean transit time. To enable quantification, susceptibility changes can be induced using gadolinium (Gd) or deoxyhemoglobin (dOHb), the latter just recently introduced as a contrast agent in DSC. Previous investigations found that experimental parameters and analysis choices, such as the susceptibility amplitude and partial volume, affect perfusion quantification. However, the accuracy and precision of DSC MRI has not been systematically investigated, particularly in the lower susceptibility range.MethodsIn this study, we compared perfusion values determined using Gd with values determined using a contrast agent with a lower susceptibility—dOHb—under different physiological conditions, such as varying the baseline blood oxygenation and/or magnitude of hypoxic bolus, by utilizing numerical simulations and conducting experiments on healthy subjects at 3T. The simulation framework we developed for DSC incorporates MRI signal contributions from intravascular and extravascular proton spins in arterial, venous, and cerebral tissue voxels. This framework allowed us to model the MRI signal in response to both Gd and dOHb.Results and discussionWe found, both in the experimental results and simulations, that a reduced intravascular volume of the selected arterial voxel, reduced baseline oxygen saturation, greater susceptibility of applied contrast agent (Gd vs. dOHb), and/or larger magnitude of applied hypoxic bolus reduces the overestimation and increases precision of cerebral blood volume and flow. As well, we found that normalizing tissue to venous rather than arterial signal increases the accuracy of perfusion quantification across experimental paradigms. Furthermore, we found that shortening the bolus duration increases the accuracy and reduces the calculated values of mean transit time. In summary, we experimentally uncovered an array of perfusion quantification dependencies, which agreed with the simulation framework predictions, using a wider range of susceptibility values than previously investigated. We argue for caution when comparing absolute and relative perfusion values within and across subjects obtained from a standard DSC MRI analysis, particularly when employing different experimental paradigms and contrast agents.
Atypical functional hierarchy contributed to the tinnitus symptoms in patients with vestibular schwannoma
Authors: Lin Jiaji , You Na , Li Xiaolong , Huang Jiayu , Lu Haoxuan , Hu Jianxing , Zhang Jun , Lou Xin 
Published: February 2023

ObjectiveTinnitus is frequently found in patients with vestibular schwannoma (VS), but its underlying mechanisms are currently unclear.MethodsBoth preoperative (VSpre) and postoperative (VSpost) functional MR images were collected from 32 patients with unilateral VS and matched healthy controls (HCs). Connectome gradients were generated for the identification of altered regions and perturbed gradient distances. Tinnitus measurements were conducted for predictive analysis with neuroimaging–genetic integration analysis.ResultsThere were 56.25% of preoperative patients and 65.63% of postoperative patients suffering from ipsilateral tinnitus, respectively. No relevant factors were identified including basic demographics info, hearing performances, tumor features, and surgical approaches. Functional gradient analysis confirmed atypical functional features of visual areas in VSpre were rescued after tumor resection, while the gradient performance in the postcentral gyrus continues to maintain (VSpost vs. HC : P = 0.016). The gradient features of the postcentral gyrus were not only significantly decreased in patients with tinnitus (PFDR = 0.022), but also significantly correlated with tinnitus handicap inventory (THI) score (r = −0.30, P = 0.013), THI level (r = −0.31, P = 0.010), and visual analog scale (VAS) rating (r = −0.31, P = 0.0093), which could be used to predict VAS rating in the linear model. Neuropathophysiological features linked to the tinnitus gradient framework were linked to Ribosome dysfunction and oxidative phosphorylation.ConclusionAltered functional plasticity in the central nervous system is involved in the maintenance of VS tinnitus.