bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of pore-throat structures of carbonate reservoirs based on petrophysical facies division
Authors: Hou Jue , Zhao Lun , Zhao Wenqi , Feng Zhao , Wang Xueke , Zeng Xing
Published: May 2023

After complex geological transformation, such as sedimentation, diagenesis, and tectonic transformation, carbonate reservoirs have developed multiple reservoir spaces with significant heterogeneity and various pore-throat structures, including pores, vugs, and fractures. Due to these characteristics, many problems have been caused during the development of carbonate reservoirs, such as large differences between the initial production capacities of single wells and serious water channeling after injection, which have brought many challenges to the efficient development of carbonate reservoirs. Therefore, based on a reservoir evaluation method of petrophysical facies, this study classified and evaluated the pore-throat structures of Carboniferous carbonate reservoirs in the North Truwa oilfield of the Pre-Caspian Basin. Based on the data of the core, thin section, scanning electron microscope, high-pressure mercury injection, sedimentary facies, diagenetic facies, and the development of fractures and karst vugs, six reservoir petrophysical facies in the study area were classified and named, including the facies of favorable sedimentation-constructive diagenesis-fracture and vug, the facies of favorable sedimentation-constructive diagenesis-non-fracture or vug, the facies of favorable sedimentation-destructive diagenesis-fracture and vug, the facies of favorable sedimentation-destructive diagenesis-non-fracture or vug, the facies of unfavorable sedimentation-constructive diagenesis-non-fracture or vug, and the facies of unfavorable sedimentation-destructive diagenesis-non-fracture or vug. The recognition and division of diagenetic facies were based on the K-nearest neighbor. Four quantitative parameters were also selected to characterize the pore-throat structures, including displacement pressure (Pd), mercury removal efficiency (Em), median throat radius (R50), and sorting coefficient (Cs). Based on the principal component analysis, the classification and evaluation standards of pore-throat structures in different petrophysical facies were established. Combined with the flow profile measured by production logging tools, the relationship between different petrophysical facies and productions was also revealed. As a result, this study can provide suggestions for the adjustment strategy of water-driven production, which lays an important foundation for the fine development of carbonate reservoirs.
Gamification into the design of the e-3D online course
Authors: dos Reis Susana Cristina , Linck Anderson José Machado , Figueiredo Max Flores , Pfeifer Diéssica Lopes
Published: May 2023

Research in the fields of Education and Applied Linguistics points to the growth of studies on digital games and gamification in Brazil. On the other hand, studies that discuss digital teaching material do not provide guidelines on how to implement gamification into the design of digital teaching materials, mainly in language studies. Thus, this work presents practical guidelines for how to explore gamification in the design of language teaching materials based on the experience developed in the outreach project laboratory of online language teaching and learning at the Federal University of Santa Maria. This research reports a case study carried out in the English online 3D course offered in the modality of distance education. To exemplify how the gamification strategies have been implemented, we provide examples from the course’s material as well as bring the user’s evaluation about participating in a gamified online course. Results indicate that gamification strategies were underpinned by exploring mainly intrinsic and extrinsic gamification strategies included in the digital material design, as well as by tools used on Moodle Platform to get the students engaged in the language learning process. On the other hand, this empirical study has shown the necessity of including more narrative strategies into the content proposed in the online course as an alternative to getting the students to explore meaningful learning by problem-solving in branching scenarios proposed inside the Moodle platform.
The change of non-alcoholic fatty liver disease is associated with risk of incident diabetes
Authors: Chen Congling , Zhang Yuecheng , Fan Yujuan , Ying Zhen , Su Qing , Li Xiaoying , Qin Li
Published: May 2023

Background & aims

The effect of change in non-alcoholic fatty liver disease (NAFLD) status on incident diabetes has not been well studied. We aimed to investigate the association of NAFLD development and remission with the risk of incident diabetes during a median of 3.5-year follow-up.

Methods

A total of 2690 participants without diabetes were recruited in 2011-2012 and assessed for incident diabetes in 2014. Abdominal ultrasonography was used to determine the change of NAFLD. 75 g oral glucose tolerance test (OGTT) was performed to determine diabetes. NAFLD severity was assessed using Gholam’s model. The odds ratios (ORs) for incident diabetes were estimated by logistic regression models.

Results

NAFLD was developed in 580 (33.2%) participants and NAFLD remission occurred in 150 (15.9%) participants during a median of 3.5-year follow-up. A total of 484 participants developed diabetes during follow-up, including 170 (14.6%) in consistent non-NAFLD group, 111 (19.1%) in NAFLD developed group, 19 (12.7%) in NAFLD remission group, and 184 (23.2%) in sustained NAFLD group. The development of NAFLD increased the risk of incident diabetes by 43% (OR, 1.43; 95%CI, 1.10-1.86) after adjustment for multiple confounders. Compared with sustained NAFLD group, remission of NAFLD reduced the risk of incident diabetes by 52% (OR, 0.48; 95%CI, 0.29-0.80). The effect of NAFLD alteration on incident diabetes was not changed after adjustment for body mass index or waist circumference, change of body mass index or waist circumference. In NAFLD remission group, participants with non-alcoholic steatohepatitis (NASH) at baseline were more likely to develop diabetes (OR, 3.03; 95%CI, 1.01-9.12).

Conclusions

NAFLD development increases the risk of incident diabetes, whereas NAFLD remission reduces the risk of incident diabetes. Moreover, presence of NASH at baseline could attenuate the protective effect of NAFLD remission on incident diabetes. Our study suggests that early intervention of NAFLD and maintenance of non-NAFLD are important for prevention of diabetes.
Patient-derived models facilitate precision medicine in liver cancer by remodeling cell-matrix interaction
Authors: Chen Kaiwen , Li Yanran , Wang Bingran , Yan Xuehan , Tao Yiying , Song Weizhou , Xi Zhifeng , He Kang , Xia Qiang
Published: May 2023

Liver cancer is an aggressive tumor originating in the liver with a dismal prognosis. Current evidence suggests that liver cancer is the fifth most prevalent cancer worldwide and the second most deadly type of malignancy. Tumor heterogeneity accounts for the differences in drug responses among patients, emphasizing the importance of precision medicine. Patient-derived models of cancer are widely used preclinical models to study precision medicine since they preserve tumor heterogeneity ex vivo in the study of many cancers. Patient-derived models preserving cell-cell and cell-matrix interactions better recapitulate in vivo conditions, including patient-derived xenografts (PDXs), induced pluripotent stem cells (iPSCs), precision-cut liver slices (PCLSs), patient-derived organoids (PDOs), and patient-derived tumor spheroids (PDTSs). In this review, we provide a comprehensive overview of the different modalities used to establish preclinical models for precision medicine in liver cancer.
Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis
Authors: Liu Pen-Ju , Yang Ting-Ting , Fan Ze-Xin , Yuan Guo-Bin , Ma Lin , Wang Ze-Yi , Lu Jian-Feng , Yuan Bo-Yi , Zou Wen-Long , Zhang Xing-Hu , Liu Guang-Zhi
Published: May 2023

Background

Increasing evidence indicates the importance of CD8+ T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8+ memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity.

Methods

The myelin oligodendrocyte glycoprotein (MOG)-specific CD8+ memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS.

Results

We found that MS patients had elevated frequency of MOG-specific CD8+ T cells, MOG-specific central memory T cells (TCM), MOG-specific CD8+ effector memory T cells (TEM), and MOG-specific CD8+ terminally differentiated cells (TEMRA); elevated granzyme B expression on MOG-specific CD8+ TCM; and, on MOG-specific CD8+ TEM, elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8+ TCM, granzyme B expression in CD8+ TCM, and granzyme B and perforin expression on CD8+ TEM, but with reduced PD-1 expression on CD8+ TEM.

Conclusion

The dysregulation of antigen-specific CD8+ memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably via molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.
Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma
Authors: Zhang Qiqi , Zu Cheng , Jing Ruirui , Feng Youqin , Zhang Yanlei , Zhang Mingming , Lv Yuqi , Cui Jiazhen , Zhou Linhui , Meng Ye , Wang Linqin , Cen Zenan , Chang Alex H. , Hu Yongxian , Huang He
Published: May 2023

Background aims

B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS.

Methods

Patients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed.

Results

Eighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3–4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p<0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5–8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.7 [95% CI 1.3–10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use.

Conclusion

TLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk.
The protective role of Lactobacillus rhamnosus GG postbiotic on the alteration of autophagy and inflammation pathways induced by gliadin in intestinal models
Authors: Furone Francesca , Bellomo Claudia , Carpinelli Martina , Nicoletti Martina , Hewa-Munasinghege Francesca Natasha , Mordaa Majed , Mandile Roberta , Barone Maria Vittoria , Nanayakkara Merlin
Published: May 2023

Celiac disease (CD) is an autoimmune enteropathy caused by an abnormal immune response to gliadin peptides in genetically predisposed individuals. For people with CD, the only available therapy thus far is the lifelong necessity for a gluten-free diet (GFD). Innovative therapies include probiotics and postbiotics as dietary supplements, both of which may benefit the host. Therefore, the present study aimed to investigate the possible beneficial effects of the postbiotic Lactobacillus rhamnosus GG (LGG) in preventing the effects induced by indigested gliadin peptides on the intestinal epithelium. In this study, these effects on the mTOR pathway, autophagic function, and inflammation have been evaluated. Furthermore, in this study, we stimulated the Caco-2 cells with the undigested gliadin peptide (P31-43) and with the crude gliadin peptic-tryptic peptides (PTG) and pretreated the samples with LGG postbiotics (ATCC 53103) (1 × 108). In this study, the effects induced by gliadin before and after pretreatment have also been investigated. The phosphorylation levels of mTOR, p70S6K, and p4EBP-1 were increased after treatment with PTG and P31-43, indicating that the intestinal epithelial cells responded to the gliadin peptides by activating the mTOR pathway. Moreover, in this study, an increase in the phosphorylation of NF-κβ was observed. Pretreatment with LGG postbiotic prevented both the activation of the mTOR pathway and the NF-κβ phosphorylation. In addition, P31-43 reduced LC3II staining, and the postbiotic treatment was able to prevent this reduction. Subsequently, to evaluate the inflammation in a more complex intestinal model, the intestinal organoids derived from celiac disease patient biopsies (GCD-CD) and controls (CTR) were cultured. Stimulation with peptide 31-43 in the CD intestinal organoids induced NF-κβ activation, and pretreatment with LGG postbiotic could prevent it. These data showed that the LGG postbiotic can prevent the P31-43-mediated increase in inflammation in both Caco-2 cells and in intestinal organoids derived from CD patients.
The benefit of co-targeting PARP-1 and c-Met on the efficacy of radiotherapy in wild type BRAF melanoma
Authors: Sabbah Malak , Najem Ahmad , Vanderkerkhove Christophe , Kert Fabien , Jourani Younes , Journe Fabrice , Awada Ahmad , Van Gestel Dirk , Ghanem Ghanem E. , Krayem Mohammad
Published: May 2023

Melanoma is known to be a radioresistant cancer. Melanoma radioresistance can be due to several factors such as pigmentation, antioxidant defenses and high Deoxyribonucleic acid (DNA) repair efficacy. However, irradiation induces intracellular translocation of RTKs, including cMet, which regulates response to DNA damage activating proteins and promotes DNA repair. Accordingly, we hypothesized that co-targeting DNA repair (PARP-1) and relevant activated RTKs, c-Met in particular, may radiosensitize wild-type B-Raf Proto-Oncogene, Serine/Threonine Kinase (WTBRAF) melanomas where RTKs are often upregulated. Firstly, we found that PARP-1 is highly expressed in melanoma cell lines. PARP-1 inhibition by Olaparib or its KO mediates melanoma cell sensitivity to radiotherapy (RT). Similarly, specific inhibition of c-Met by Crizotinib or its KO radiosensitizes the melanoma cell lines. Mechanistically, we show that RT causes c-Met nuclear translocation to interact with PARP-1 promoting its activity. This can be reversed by c-Met inhibition. Accordingly, RT associated with the inhibition of both c-Met and PARP-1 resulted in a synergistic effect not only on tumor growth inhibition but also on tumor regrowth control in all animals following the stop of the treatment. We thus show that combining PARP and c-Met inhibition with RT appears a promising therapeutic approach in WTBRAF melanoma.
Whole genome sequencing of Ethiopian Brucella abortus isolates expands the known diversity of an early branching sub-Saharan African lineage
Authors: Edao Bedaso Mammo , Ameni Gobena , Berg Stefan , Tekle Muluken , Whatmore Adrian M. , Wood James L. N. , van Tonder Andries J. , Ashford Roland T.
Published: May 2023

Brucellosis remains one of the most significant zoonotic diseases globally, responsible for both considerable human morbidity and economic losses due to its impacts on livestock productivity. Despite this, there remain significant evidence gaps in many low- and middle-income countries, including those of sub-Saharan Africa. Here we report the first molecular characterisation of Brucella sp. from Ethiopia. Fifteen Brucella sp. isolates from an outbreak in cattle from a herd in central Ethiopia were identified as Brucella abortus, using bacterial culture and molecular methods. Sequencing of the Ethiopian B. abortus isolates allowed their phylogenetic comparison with 411 B. abortus strains of diverse geographical origins, using whole genome single nucleotide polymorphisms (wgSNP). The Ethiopian isolates belonged to an early-branching lineage (Lineage A) previously only represented by data from two strains, both of sub-Saharan African origin (Kenya and Mozambique). A second B. abortus lineage (Lineage B), also comprised solely of strains originating from sub-Saharan Africa, was identified. The majority of strains belonged to one of two lineages of strains originating from a much broader geographical range. Further analyses based on multi-locus sequence typing (MLST) and multi-locus variable-number tandem repeat analysis (MLVA) expanded the number of B. abortus strains available for comparison with the Ethiopian isolates and were consistent with the findings from wgSNP analysis. MLST profiles of the Ethiopian isolates expanded the sequence type (ST) diversity of the early branching lineage of B. abortus, equivalent to wgSNP Lineage A. A more diverse cluster of STs, equivalent to wgSNP Lineage B, was comprised solely of strains originating from sub-Saharan Africa. Similarly, analysis of B. abortus MLVA profiles (n = 1891) confirmed that the Ethiopian isolates formed a unique cluster, similar to only two existing strains, and distinct from the majority of other strains of sub-Saharan African origin. These findings expand the known diversity of an under-represented lineage of B. abortus and suggest a potential evolutionary origin for the species in East Africa. In addition to providing information concerning Brucella species extant within Ethiopia this work serves as the basis for further studies on the global population structure and evolutionary history of a major zoonotic pathogen.
Expanding the taxonomic and environmental extent of an underexplored carbon metabolism—oxalotrophy
Authors: Sonke Alexander , Trembath-Reichert Elizabeth
Published: May 2023

Oxalate serves various functions in the biological processes of plants, fungi, bacteria, and animals. It occurs naturally in the minerals weddellite and whewellite (calcium oxalates) or as oxalic acid. The environmental accumulation of oxalate is disproportionately low compared to the prevalence of highly productive oxalogens, namely plants. It is hypothesized that oxalotrophic microbes limit oxalate accumulation by degrading oxalate minerals to carbonates via an under-explored biogeochemical cycle known as the oxalate-carbonate pathway (OCP). Neither the diversity nor the ecology of oxalotrophic bacteria is fully understood. This research investigated the phylogenetic relationships of the bacterial genes oxc, frc, oxdC, and oxlT, which encode key enzymes for oxalotrophy, using bioinformatic approaches and publicly available omics datasets. Phylogenetic trees of oxc and oxdC genes demonstrated grouping by both source environment and taxonomy. All four trees included genes from metagenome-assembled genomes (MAGs) that contained novel lineages and environments for oxalotrophs. In particular, sequences of each gene were recovered from marine environments. These results were supported with marine transcriptome sequences and description of key amino acid residue conservation. Additionally, we investigated the theoretical energy yield from oxalotrophy across marine-relevant pressure and temperature conditions and found similar standard state Gibbs free energy to “low energy” marine sediment metabolisms, such as anaerobic oxidation of methane coupled to sulfate reduction. These findings suggest further need to understand the role of bacterial oxalotrophy in the OCP, particularly in marine environments, and its contribution to global carbon cycling.
Comprehensive analysis of codon bias in 13 Ganoderma mitochondrial genomes
Authors: Wu Peng , Xiao Wenqi , Luo Yingyong , Xiong Zhuang , Chen Xiaodie , He Jing , Sha Ajia , Gui Mingying , Li Qiang
Published: May 2023

Introduction

Codon usage bias is a prevalent phenomenon observed across various species and genes. However, the specific attributes of codon usage in the mitochondrial genome of Ganoderma species remain unknown.

Methods

In this study, we investigated the codon bias of 12 mitochondrial core protein-coding genes (PCGs) in 9 Ganoderma species, including 13 Ganoderma strains.

Results

The codons of all Ganoderma strains showed a preference for ending in A/T. Additionally, correlations between codon base composition and the codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) were identified, demonstrating the impact of base composition on codon bias. Various base bias indicators were found to vary between or within Ganoderma strains, including GC3s, the CAI, the CBI, and the FOP. The results also revealed that the mitochondrial core PCGs of Ganoderma have an average effective number of codons (ENC) lower than 35, indicating strong bias toward certain codons. Evidence from neutrality plot and PR2-bias plot analysis indicates that natural selection is a major factor affecting codon bias in Ganoderma. Additionally, 11 to 22 optimal codons (ΔRSCU>0.08 and RSCU>1) were identified in 13 Ganoderma strains, with GCA, AUC, and UUC being the most widely used optimal codons in Ganoderma. By analyzing the combined mitochondrial sequences and relative synonymous codon usage (RSCU) values, the genetic relationships between or within Ganoderma strains were determined, indicating variations between them. Nevertheless, RSCU-based analysis illustrated the intra- and interspecies relationships of certain Ganoderma species.

Discussion

This study deepens our insight into the synonymous codon usage characteristics, genetics, and evolution of this important fungal group.
A biochemical, theoretical and immunohistochemical study comparing the therapeutic efficacy of curcumin and taurine on T-2 toxin induced hepatotoxicity in rats
Authors: Al-Zahrani Maryam H. , Balgoon Maha J. , El-Sawi Nagwa M. , Alshubaily Fawzia A. , Jambi Ebtihaj J. , Khojah Sohair M. , Baljoon Raghad S. , Alkhattabi Nuha A. , Baz Lina A. , Alharbi Asmaa A. , Ahmed Amira M. , Abo elkhair Ayat M. , Ismael Mohamed , Gebril Sahar M.
Published: May 2023

Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity.

Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done.

Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin’s therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin’s higher binding affinity than taurine.

Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin.
Alzheimer's disease pathology: pathways between chronic vascular risk factors and blood-brain barrier dysfunction in a cohort of patients with different types of dementia
Authors: Gan Jinghuan , Yang Xia , Zhang Guili , Li Xudong , Liu Shuai , Zhang Wei , Ji Yong
Published: May 2023

Background

Blood brain barrier (BBB) breakdown is considered a potential mechanism of dementia. The Alzheimer's disease (AD) biomarkers and vascular factors are also associated with BBB permeability.

Objective

In the present study, the combination effects of neuropathological biomarkers of AD and chronic vascular risk factors for BBB were investigated.

Methods

The cerebrospinal fluid (CSF)/serum albumin ratio (Qalb), an indicator of BBB permeability, was measured in a total of 95 hospitalized dementia patients. The demographics, clinical information, and laboratory tests were collected from the inpatient records. The CSF neuropathological biomarkers of AD and apolipoprotein E (APOE) genotype were also collected. The mediation analysis model was used to calculate the associations among neuropathological biomarkers of AD (mediator), the Qalb, and chronic vascular risk factors.

Results

Three types of dementia, AD (n = 52), Lewy body dementia (LBD, n = 19), and frontotemporal lobar degeneration (n = 24), were included with a mean Qalb of 7.18 (± 4.36). The Qalb was significantly higher in dementia patients with type 2 diabetes mellitus (T2DM, p = 0.004) but did not differ based on the presence of APOE ε4 allele, CMBs, or amyloid/tau/neurodegeneration (ATN) framework. The Qalb was negatively associated with the levels of Aβ1-42 (B = −20.775, p = 0.009) and Aβ1-40 (B = −305.417, p = 0.005) and positively associated with the presence of T2DM (B = 3.382, p < 0.001) and the levels of glycosylated hemoglobin (GHb, B = 1.163, p < 0.001) and fasting blood glucose (FBG, B = 1.443, p < 0.001). GHb is a direct chronic vascular risk factor for higher Qalb (total effect B = 1.135, 95% CI: 0.611–1.659, p < 0.001). Ratios of Aβ1-42/Aβ1-40 or t-tau/Aβ1-42 were mediators of the association between the Qalb and GHb; the direct effect of GHb on the Qalb was 1.178 (95% CI: 0.662–1.694, p < 0.001).

Conclusion

Glucose exposure can directly or indirectly affect BBB integrity through Aβ and tau, indicating glucose affects BBB breakdown and glucose stability plays an important role in dementia protection and management.
The combined associations of depression and cognitive impairment with functional disability and mortality in older adults: a population-based study from the NHANES 2011–2014
Authors: Han Shuang , Gao Yue , Gan Da
Published: May 2023

Objective

The present study aimed to explore the combined associations of depression and cognitive impairment with functional disability and mortality, and whether the joint effects of depression and cognitive impairment on mortality were influenced by functional disability.

Methods

A total of 2,345 participants aged 60 and above from the 2011–2014 cycle of the National Health and Nutrition Examination Survey (NHANES) were included in the analyses. Questionnaires were used to evaluated depression, global cognitive function and functional disability (including disability in activities of daily living (ADLs), instrumental activities of daily living (IADLs), leisure and social activities (LSA), lower extremity mobility (LEM), and general physical activity (GPA)). Mortality status was ascertained up to December 31, 2019. Multivariable logistic regression was performed to investigate the associations of depression and low global cognition with functional disability. Cox proportional hazards regression models were conducted to evaluate the effect of depression and low global cognition on mortality.

Results

Interactions between depression and low global cognition were observed when exploring associations of depression and low global cognition with IADLs disability, LEM disability, and cardiovascular mortality. Compared with normal participants, participants with both depression and low global cognition had the highest odds ratios of disability in ADLs, IADLs, LSA, LEM, and GPA. Besides, participants with both depression and low global cognition also had the highest hazard ratios of all-cause mortality and cardiovascular mortality, and these associations remained after adjusting for disability in ADLs, IADLs, LSA, LEM, and GPA.

Conclusion

Older adults with both depression and low global cognition were more likely to have functional disability, and had the highest risk of all-cause mortality and cardiovascular mortality.
Need for personalized monitoring of Parkinson’s disease: the perspectives of patients and specialized healthcare providers
Authors: Evers Luc J. W. , Peeters José M. , Bloem Bastiaan R. , Meinders Marjan J.
Published: May 2023

Background

Digital tools such as wearable sensors may help to monitor Parkinson’s disease (PD) in daily life. To optimally achieve the expected benefits, such as personized care and improved self-management, it is essential to understand the perspective of both patients and the healthcare providers.

Objectives

We identified the motivations for and barriers against monitoring PD symptoms among PD patients and healthcare providers. We also investigated which aspects of PD were considered most important to monitor in daily life, and which benefits and limitations of wearable sensors were expected.

Methods

Online questionnaires were completed by 434 PD patients and 166 healthcare providers who were specialized in PD care (86 physiotherapists, 55 nurses, and 25 neurologists). To gain further understanding in the main findings, we subsequently conducted homogeneous focus groups with patients (n = 14), physiotherapists (n = 5), and nurses (n = 6), as well as individual interviews with neurologists (n = 5).

Results

One third of the patients had monitored their PD symptoms in the past year, most commonly using a paper diary. Key motivations were: (1) discuss findings with healthcare providers, (2) obtain insight in the effect of medication and other treatments, and (3) follow the progression of the disease. Key barriers were: (1) not wanting to focus too much on having PD, (2) symptoms being relatively stable, and (3) lacking an easy-to-use tool. Prioritized symptoms of interest differed between patients and healthcare providers; patients gave a higher priority to fatigue, problems with fine motor movements and tremor, whereas professionals more frequently prioritized balance, freezing and hallucinations. Although both patients and healthcare providers were generally positive about the potential of wearable sensors for monitoring PD symptoms, the expected benefits and limitations varied considerably between groups and within the patient group.

Conclusion

This study provides detailed information about the perspectives of patients, physiotherapists, nurses and neurologists on the merits of monitoring PD in daily life. The identified priorities differed considerably between patients and professionals, and this information is critical when defining the development and research agenda for the coming years. We also noted considerable differences in priorities between individual patients, highlighting the need for personalized disease monitoring.
Insights into nanoparticles-induced neurotoxicity and cope up strategies
Authors: Zia Sana , Islam Aqib Amjad , Muneer Afshan , Fatima Mahreen , Atta Khazeena , Kausar Tasleem , Zaheer C-Neen Fatima , Ahmad Irfan , Saeed Mohd , Shafique Asyia
Published: May 2023

Nanoparticle applications are becoming increasingly popular in fields such as photonics, catalysis, magnetics, biotechnology, manufacturing of cosmetics, pharmaceuticals, and medicines. There is still a huge pile of undermining information about the potential toxicity of these products to humans, which can be encountered by neuroprotective antioxidants and anti-inflammatory compounds. Nanoparticles can be administered using a variety of methods, including oronasal, topical applications, and enteral and parenteral routes of administration. There are different properties of these nanomaterials that characterize different pathways. Crossing of the blood-brain barrier, a direct sensory nerve-to-brain pathway whose barriers are bypassed, these checks otherwise prevent the nanoparticles from entering the brain. This inflicts damage to sensory neurons and receptors by nanoparticles that lead to neurotoxicity of the central nervous system. A number of routes make nanoparticles able to penetrate through the skin. Exposure by various routes to these nanoparticles can result in oxidative stress, and immune suppression triggers inflammatory cascades and genome-level mutations after they are introduced into the body. To out-power, these complications, plant-based antioxidants, essential oils, and dietary supplements can be put into use. Direct nanoparticle transport pathways from sensory nerves to the brain via blood have been studied grossly. Recent findings regarding the direct pathways through which nanoparticles cross the blood-brain barriers, how nanoparticles elicit different responses on sensory receptors and nerves, how they cause central neurotoxicity and neurodegeneration through sensory nerve routes, and the possible mechanisms that outcast these effects are discussed.
GCF2-Net: global-aware cross-modal feature fusion network for speech emotion recognition
Authors: Li Feng , Luo Jiusong , Wang Lingling , Liu Wei , Sang Xiaoshuang
Published: May 2023

Emotion recognition plays an essential role in interpersonal communication. However, existing recognition systems use only features of a single modality for emotion recognition, ignoring the interaction of information from the different modalities. Therefore, in our study, we propose a global-aware Cross-modal feature Fusion Network (GCF2-Net) for recognizing emotion. We construct a residual cross-modal fusion attention module (ResCMFA) to fuse information from multiple modalities and design a global-aware module to capture global details. More specifically, we first use transfer learning to extract wav2vec 2.0 features and text features fused by the ResCMFA module. Then, cross-modal fusion features are fed into the global-aware module to capture the most essential emotional information globally. Finally, the experiment results have shown that our proposed method has significant advantages than state-of-the-art methods on the IEMOCAP and MELD datasets, respectively.
Development of brain-penetrable antibody radioligands for in vivo PET imaging of amyloid-β and tau
Authors: Banka Vinay , Kelleher Andrew , Sehlin Dag , Hultqvist Greta , Sigurdsson Einar M. , Syvänen Stina , Ding Yu-Shin
Published: May 2023

Introduction

Alzheimer's disease (AD) is characterized by the misfolding and aggregation of two major proteins: amyloid-beta (Aβ) and tau. Antibody-based PET radioligands are desirable due to their high specificity and affinity; however, antibody uptake in the brain is limited by the blood–brain barrier (BBB). Previously, we demonstrated that antibody transport across the BBB can be facilitated through interaction with the transferrin receptor (TfR), and the bispecific antibody-based PET ligands were capable of detecting Aβ aggregates via ex vivo imaging. Since tau accumulation in the brain is more closely correlated with neuronal death and cognition, we report here our strategies to prepare four F-18-labeled, specifically engineered bispecific antibody probes for the selective detection of tau and Aβ aggregates to evaluate their feasibility and specificity, particularly for in vivo PET imaging.

Methods

We first created and evaluated (via both in vitro and ex vivo studies) four specifically engineered bispecific antibodies, by fusion of single-chain variable fragments (scFv) of a TfR antibody with either a full-size IgG antibody of Aβ or tau or with their respective scFv. Using [18F]SFB as the prosthetic group, all four 18F-labeled bispecific antibody probes were then prepared by conjugation of antibody and [18F]SFB in acetonitrile/0.1 M borate buffer solution (final pH ∼ 8.5) with an incubation of 20 min at room temperature, followed by purification on a PD MiniTrap G-25 size-exclusion gravity column.

Results

Based on both in vitro and ex vivo evaluation, the bispecific antibodies displayed much higher brain concentrations than the unmodified antibody, supporting our subsequent F18-radiolabeling. [18F]SFB was produced in high yields in 60 min (decay-corrected radiochemical yield (RCY) 46.7 ± 5.4) with radiochemical purities of >95%, confirmed by analytical high-performance liquid chromatography (HPLC) and radio-TLC. Conjugation of [18F]SFB and bispecific antibodies showed a conversion efficiency of 65%-83% with radiochemical purities of 95%–99% by radio-TLC.

Conclusions

We successfully labeled four novel and specifically engineered bispecific antibodies with [18F]SFB under mild conditions with a high RCY and purities. This study provides strategies to create brain-penetrable F-18 radiolabeled antibody probes for the selective detection of tau and Aβ aggregates in the brain of transgenic AD mice via in vivo PET imaging.
Infant burn injuries related to water heating for powdered infant formula preparation
Authors: Chiang Katelyn V. , Anstey Erica H. , Abrams Steven A. , Perrine Cria G.
Published: May 2023

Background

Guidance for preparing powdered infant formula (PIF) helps to ensure it meets the nutritional needs of infants and is safe to consume. Among safety concerns is Cronobacter sakazakii contamination which can lead to serious infections and death. PIF preparation guidance varies; there is a lack of consensus on whether there is a need to boil water to inactivate potential Cronobacter and for how long to let the water cool before reconstitution. We sought to quantify the burden of burn injuries among infants related to water heating for PIF preparation. Estimating this burden may help inform preparation recommendations.

Methods

Burn injuries among infants <18 months of age were identified from 2017 to 2019 National Electronic Injury Surveillance System data collected from sampled hospital emergency departments. Injuries were classified as related to PIF water heating, potentially related to PIF water heating but with undetermined causation, related to other infant feeding aspects, or unrelated to infant formula or breast milk feeding. Unweighted case counts for each injury classification were determined.

Results

Across sampled emergency departments, 7 PIF water heating injuries were seen among the 44,395 injuries reported for infants <18 months. No reported PIF water heating injuries were fatal, but 3 required hospitalization. Another 238 injuries potentially related to PIF water heating but with undetermined causation were also seen.

Conclusion

Preparation guidance should consider both the potential risk for Cronobacter infection and the potential risk for burns.
Advances in symptomatic therapy for left ventricular non-compaction in children
Authors: Li Dong , Wang Ce
Published: May 2023

Left ventricular non-compaction is a complex cardiomyopathy and the third largest childhood cardiomyopathy, for which limited knowledge is available. Both pathogenesis and prognosis are still under investigation. Currently, no effective treatment strategy exists to reduce its incidence or severity, and symptomatic treatment is the only clinical treatment strategy. Treatment strategies are constantly explored in clinical practice, and some progress has been made in coping with the corresponding symptoms because the prognosis of children with left ventricular non-compaction is usually poor if there are complications. In this review, we summarized and discussed the coping methods for different left ventricular non-compaction symptoms.
Prenatal opioid exposure and risk of asthma in childhood: a population-based study from Denmark, Norway, and Sweden
Authors: Odsbu Ingvild , Handal Marte , Hjellvik Vidar , Hernandez-Diaz Sonia , Kieler Helle , Nørgaard Mette , Skurtveit Svetlana , Esen Buket Öztürk , Mahic Milada
Published: May 2023

Background: Opioids may modulate the immune function through opioid receptors on immune cells. Long-term consequences of prenatal opioid exposure on the immune system, such as childhood asthma, are unknown.

Objectives: To investigate whether prenatal opioid exposure is associated with the risk of childhood asthma.

Methods: Cohort study using linked nationwide registers in Denmark (1996–2015), Norway (2005–2015), and Sweden (2006–2013). Children born by mothers who were chronic opioid analgesics users before pregnancy (n = 14,764) or who were receiving opioid maintenance therapy (OMT) before or during pregnancy (n = 1,595) were identified based on information from each of the medical birth registers and prescription registers. Long-term opioid analgesics exposed children were compared to short-term exposed or unexposed, whereas OMT exposed children were compared to OMT unexposed. Asthma among children ≥1 years of age was defined as two or more filled prescriptions of antiasthmatic medication within 365 days, or a diagnosis of asthma. Hazard ratios (HRs) were calculated using Cox proportional hazards regression with attained age as the time scale. Inverse probability of treatment weights based on propensity scores were applied to adjust for measured confounders. Individual level data from Norway and Sweden were pooled, whereas individual level data from Denmark were analyzed separately. For the opioid analgesics comparisons, adjusted HRs (aHR) from the combined Norwegian/Swedish data and the Danish data were pooled in a fixed-effects meta-analysis.

Results: For the opioid analgesics cohort, no increased risk of asthma was observed in long-term exposed children neither compared with unexposed [aHR = 0.99 (95% CI 0.87-1.12)], nor compared with short-term exposed [aHR = 0.97 (0.86-1.10)]. No increased risk of asthma was observed in OMT exposed compared with OMT unexposed children [Norway/Sweden: aHR = 1.07 (0.60-1.92), Denmark: aHR = 1.25 (0.87-1.81)]. Results from sensitivity analyses, where potential misclassification of the outcome and misclassification of OMT exposure were assessed, as well as starting follow-up at 6 years of age, showed that the estimates of association were generally robust.

Conclusion: We found no association between prenatal exposure to opioids and risk of childhood asthma. Results were consistent across two different opioid exposure groups with different confounder distributions.
Emerging trends and focus on immune checkpoint inhibitors for non-small cell lung cancer treatment: visualization and bibliometric analysis
Authors: Zhang Yue , Lu Lishan , Zheng Rui
Published: May 2023

Introduction: Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small cell lung carcinoma (NSCLC) accounts for approximately 80% of all cases. Immune checkpoint inhibitors (ICIs) are widely used to treat NSCLC owing to their remarkable efficacy. In this study, we analyzed the scientific collaboration network, defined the hotspots of research on the use of ICIs for NSCLC treatment, analyzed its evolution over the past few years, and forecasted the field’s future development using bibliometric analysis and a graphical study.

Methods: Research articles and reviews regarding ICIs for NSCLC were retrieved and obtained from the Web of Science Core Collection on 26 September 2022. CtieSpace and VOSviewer were thereafter used to conduct the bibliometric and knowledge-map analysis.

Results: We included 8,149 articles for this literature analysis. Our analysis showed that the USA had the highest number of publications and citations. We also noted that research trends in this field have changed drastically over the past 20 years, from the early development of ICIs, such as CTLA-4 inhibitors, to the development of recent ones, such as PD-1 and PD-L1 blockers. Further, the focus of research in this field has also gradually shifted from mechanisms to treatment effects and adverse events, suggesting that the field is maturing. Clinical applications are also being explored, including studies on how to enhance efficacy, reduce adverse effects, and expand to other specific cancer types.

Conclusion: To the best of our knowledge, this is the first study to construct a comprehensive knowledge map on ICIs for NSCLC. It can help researchers rapidly grasp the status and focus of current research in this area, offer direction, and serve as a reference for conducting similar studies.