bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Genomics-Based Approaches for Defining Allograft Rejection With Single Cell Resolution
Authors: Shi Tiffany , Roskin Krishna , Baker Brian M. , Woodle E. Steve , Hildeman David
Published: October 2021

Solid organ transplant recipients require long-term immunosuppression for prevention of rejection. Calcineurin inhibitor (CNI)-based immunosuppressive regimens have remained the primary means for immunosuppression for four decades now, yet little is known about their effects on graft resident and infiltrating immune cell populations. Similarly, the understanding of rejection biology under specific types of immunosuppression remains to be defined. Furthermore, development of innovative, rationally designed targeted therapeutics for mitigating or preventing rejection requires a fundamental understanding of the immunobiology that underlies the rejection process. The established use of microarray technologies in transplantation has provided great insight into gene transcripts associated with allograft rejection but does not characterize rejection on a single cell level. Therefore, the development of novel genomics tools, such as single cell sequencing techniques, combined with powerful bioinformatics approaches, has enabled characterization of immune processes at the single cell level. This can provide profound insights into the rejection process, including identification of resident and infiltrating cell transcriptomes, cell-cell interactions, and T cell receptor α/β repertoires. In this review, we discuss genomic analysis techniques, including microarray, bulk RNAseq (bulkSeq), single-cell RNAseq (scRNAseq), and spatial transcriptomic (ST) techniques, including considerations of their benefits and limitations. Further, other techniques, such as chromatin analysisviaassay for transposase-accessible chromatin sequencing (ATACseq), bioinformatic regulatory network analyses, and protein-based approaches are also examined. Application of these tools will play a crucial role in redefining transplant rejection with single cell resolution and likely aid in the development of future immunomodulatory therapies in solid organ transplantation.
Antibody-Mediated Targeting of Antigens to Intestinal Aminopeptidase N Elicits Gut IgA Responses in Pigs
Authors: Van der Weken Hans , Sanz Garcia Raquel , Sanders Niek N. , Cox Eric , Devriendt Bert
Published: October 2021

Many pathogens enter the host via the gut, causing disease in animals and humans. A robust intestinal immune response is necessary to protect the host from these gut pathogens. Despite being best suited for eliciting intestinal immunity, oral vaccination remains a challenge due to the gastrointestinal environment, a poor uptake of vaccine antigens by the intestinal epithelium and the tolerogenic environment pervading the gut. To improve uptake, efforts have focused on targeting antigens towards the gut mucosa. An interesting target is aminopeptidase N (APN), a conserved membrane protein present on small intestinal epithelial cells shown to mediate epithelial transcytosis. Here, we aimed to further optimize this oral vaccination strategy in a large animal model. Porcine APN-specific monoclonal antibodies were generated and the most promising candidate in terms of epithelial transcytosis was selected to generate antibody fusion constructs, comprising a murine IgG1 or porcine IgA backbone and a low immunogenic antigen: the F18-fimbriated E. coli tip adhesin FedF. Upon oral delivery of these recombinant antibodies in piglets, both mucosal and systemic immune responses were elicited. The presence of the FedF antigen however appeared to reduce these immune responses. Further analysis showed that F18 fimbriae were able to disrupt the antigen presenting capacity of intestinal antigen presenting cells, implying potential tolerogenic effects of FedF. Altogether, these findings show that targeted delivery of molecules to epithelial aminopeptidase N results in their transcytosis and delivery to the gut immune systems. The results provide a solid foundation for the development of oral subunit vaccines to protect against gut pathogens.
Decreased miR-4512 Levels in Monocytes and Macrophages of Individuals With Systemic Lupus Erythematosus Contribute to Innate Immune Activation and Neutrsophil NETosis by Targeting TLR4 and CXCL2
Authors: Yang Binbin , Huang Xinwei , Xu Shuangyan , Li Li , Wu Wei , Dai Yunjia , Ge Ming-Xia , Yuan Limei , Cao Wenting , Yang Meng , Wu Yongzhuo , Deng Danqi
Published: October 2021

Objective

Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology that is not yet entirely understood. We aimed to elucidate the mechanisms and therapeutic potential of microRNAs (miRNAs) in SLE in a Tibetan population.

Methods

Peripheral blood mononuclear cells from SLE patients (n = 5) and healthy controls (n = 5) were used for miRNA–mRNA co-sequencing to detect miRNAs related to immune abnormalities associated with SLE. Luciferase reporter assay was used to identify potential targets of candidate miRNA. The target genes were verified in miRNA-agomir/antagomir transfection assays with multiple cells lines and by expression analysis. The effects of candidate miRNA on monocyte and macrophage activation were evaluated by multiple cytokine profiling. Neutrophil extracellular traps (NETs) formation was analyzed in vitro by cell stimulation with supernatants of monocytes and macrophages transfected with candidate miRNA. The rodent MRL/lpr lupus model was used to evaluate the therapeutic effect of CXCL2Ab on SLE and the regulation effect of immune disorders.

Results

Integrated miRNA and mRNA expression profiling identified miRNA-4512 as a candidate miRNA involved in the regulation of neutrophil activation and chemokine-related pathways. MiR-4512 expression was significantly reduced in monocytes and macrophages from SLE patients. MiR-4512 suppressed the TLR4 pathway by targeting TLR4 and CXCL2. Decreased monocyte and macrophage miR-4512 levels led to the expression of multiple proinflammatory cytokines in vitro. Supernatants of miR-4512 antagomir-transfected monocytes and macrophages significantly promoted NETs formation (P < 0.05). Blocking of CXCL2 alleviated various pathogenic manifestations in MRL/lpr mice, including kidney damage and expression of immunological markers of SLE.

Conclusions

We here demonstrated the role of miR-4512 in innate immunity regulation in SLE. The effect of miR-4512 involves the regulation of monocytes, macrophages, and NETs formation by direct targeting of TLR4 and CXCL2, indicating the miR-4512-TLR4-CXCL2 axis as a potential novel therapeutic target in SLE.
Patterns and Trends in Cetacean Occurrence Revealed by Shorewatch, a Land-Based Citizen Science Program in Scotland (United Kingdom)
Authors: Gutiérrez-Muñoz Paula , Walters Alice E. M. , Dolman Sarah J. , Pierce Graham J.
Published: October 2021

Shorewatch is a citizen science project, managed by Whale and Dolphin Conservation (WDC), that records the occurrence of cetaceans during regular, standardized watches from a series of locations along the coast of Scotland (United Kingdom). Observer training and a clearly defined protocol help deliver a valuable source of information about cetacean occurrence and activity along the coast. Between 2005–2018, over 52000 watches generated over 11000 sightings of at least 18 cetacean species. Generalized Additive Models based on sightings for the five most commonly sighted species (bottlenose dolphin, harbor porpoise, minke whale, Risso’s dolphin, and common dolphin), at those sites with the longest time series, demonstrated seasonal, geographical and year-to-year differences in their local occurrence and relative abundance. Bottlenose dolphins are mainly present at observation sites located on the east coast of Scotland, being uncommon on the west coast, while harbor porpoise and minke whale are principally present at sites located on the west coast. The seasonality observed in cetacean occurrence is consistent with peak abundance in summer months described by previous studies in the area. Mean depth around the observation sites is the static variable that apparently has the greatest influence on species presence and number of sightings, except for Risso’s dolphin. All the species except bottlenose dolphin showed upward trends in occurrence and number of sightings over the period 2012–2018. Evidence of temporal autocorrelation was found between results from consecutive watches at the same site on the same day as well as between results from consecutive days at the same site. The power to detect declines in local abundance over a 6-year period depends on the underlying sighting rate of each cetacean species, the number of watches performed and the rate of decline. Simulations performed to determine the power to detect a decline suggest that the current intensity of observation effort in some observation sites, of about 2500 watches per year, may offer good prospects of detecting a 30% decline of the most frequently sighted species (95% of the time) over a 6-year period, although a more even distribution of observation effort in space and time is desirable. The data could potentially be used for monitoring and 6-yearly reporting of the status of cetacean populations.
Critical Shear Stress for Erosion of Sand-Mud Mixtures and Pure Mud
Authors: Chen Dake , Zheng Jinhai , Zhang Chi , Guan Dawei , Li Yuan , Wang Yigang
Published: October 2021

The erosion threshold of sand-mud mixtures is investigated by analyzing the momentum balance of a sand particle or a mud parcel in the mixture bed surface, and a formula for the critical shear stress of sand-mud mixtures is developed, which also applies for pure sand and mud. The developed formula suggests that the variation of the critical shear stress of sand-mud mixtures over mud content is mainly caused by the varying dry bulk density of the mud component in the mixture. The developed formula reproduces well the variation of the critical shear stress of sand-mud mixtures over mud content and can predict the critical shear stress of both sand-mud mixtures and pure mud in the process of consolidation. The developed formula promises to be convenient for application by relating the critical shear stress to mud content and the dry bulk density of sediment.
Construction and Identification of a Novel 5-Gene Signature for Predicting the Prognosis in Breast Cancer
Authors: Guo Lingling , Jing Yu
Published: October 2021

Background: Breast cancer is one of the most common malignancies in women worldwide. The purpose of this study was to identify the hub genes and construct prognostic signature that could predict the survival of patients with breast cancer (BC).

Methods: We identified differentially expressed genes between the responder group and non-responder group based on the GEO cohort. Drug-resistance hub genes were identified by weighted gene co-expression network analysis, and a multigene risk model was constructed by univariate and multivariate Cox regression analysis based on the TCGA cohort. Immune cell infiltration and mutation characteristics were analyzed.

Results: A 5-gene signature (GP6, MAK, DCTN2, TMEM156, and FKBP14) was constructed as a prognostic risk model. The 5-gene signature demonstrated favorable prediction performance in different cohorts, and it has been confirmed that the signature was an independent risk indicater. The nomogram comprising 5-gene signature showed better performance compared with other clinical features, Further, in the high-risk group, high M2 macrophage scores were related with bad prognosis, and the frequency of TP53 mutations was greater in the high-risk group than in the low-risk group. In the low-risk group, high CD8+ T cell scores were associated with a good prognosis, and the frequency of CDH1 mutations was greater in the low-risk group than that in the high-risk group. At the same time, patients in the low risk group have a good response to immunotherapy in terms of immunotherapy. The results of immunohistochemistry showed that MAK, GP6, and TEMEM156 were significantly highly expressed in tumor tissues, and DCTN2 was highly expressed in normal tissues.

Conclusions: Our study may find potential new targets against breast cancer, and provide new insight into the underlying mechanisms.
Application of in silico Platform for the Development and Optimization of Fully Bioresorbable Vascular Scaffold Designs
Authors: Milosevic Miljan , Anic Milos , Nikolic Dalibor , Geroski Vladimir , Milicevic Bogdan , Kojic Milos , Filipovic Nenad
Published: October 2021

Bioresorbable vascular scaffolds (BVS), made either from polymers or from metals, are promising materials for treating coronary artery disease through the processes of percutaneous transluminal coronary angioplasty. Despite the opinion that bioresorbable polymers are more promising for coronary stents, their long-term advantages over metallic alloys have not yet been demonstrated. The development of new polymer-based BVS or optimization of the existing ones requires engineers to perform many very expensive mechanical tests to identify optimal structural geometry and material characteristics. in silico mechanical testing opens the possibility for a fast and low-cost process of analysis of all the mechanical characteristics and also provides the possibility to compare two or more competing designs. In this study, we used a recently introduced material model of poly-l-lactic acid (PLLA) fully bioresorbable vascular scaffold and recently empowered numerical InSilc platform to perform in silico mechanicals tests of two different stent designs with different material and geometrical characteristics. The result of inflation, radial compression, three-point bending, and two-plate crush tests shows that numerical procedures with true experimental constitutive relationships could provide reliable conclusions and a significant contribution to the optimization and design of bioresorbable polymer-based stents.
Targeted Delivery of Narrow-Spectrum Protein Antibiotics to the Lower Gastrointestinal Tract in a Murine Model of Escherichia coli Colonization
Authors: Carpena Nuria , Richards Kerry , Bello Gonzalez Teresita D. J. , Bravo-Blas Alberto , Housden Nicholas G. , Gerasimidis Konstantinos , Milling Simon W. F. , Douce Gillian , Malik Danish J. , Walker Daniel
Published: October 2021

Bacteriocins are narrow-spectrum protein antibiotics that could potentially be used to engineer the human gut microbiota. However, technologies for targeted delivery of proteins to the lower gastrointestinal (GI) tract in preclinical animal models are currently lacking. In this work, we have developed methods for the microencapsulation of Escherichia coli targeting bacteriocins, colicin E9 and Ia, in a pH responsive formulation to allow their targeted delivery and controlled release in an in vivo murine model of E. coli colonization. Membrane emulsification was used to produce a water-in-oil emulsion with the water-soluble polymer subsequently cross-linked to produce hydrogel microcapsules. The microcapsule fabrication process allowed control of the size of the drug delivery system and a near 100% yield of the encapsulated therapeutic cargo. pH-triggered release of the encapsulated colicins was achieved using a widely available pH-responsive anionic copolymer in combination with alginate biopolymers. In vivo experiments using a murine E. coli intestinal colonization model demonstrated that oral delivery of the encapsulated colicins resulted in a significant decrease in intestinal colonization and reduction in E. coli shedding in the feces of the animals. Employing controlled release drug delivery systems such as that described here is essential to enable delivery of new protein therapeutics or other biological interventions for testing within small animal models of infection. Such approaches may have considerable value for the future development of strategies to engineer the human gut microbiota, which is central to health and disease.
Site and Bioenergy Cropping System Similarly Affect Distinct Live and Total Soil Microbial Communities
Authors: Leichty Sarah I. , Kasanke Christopher P. , Bell Sheryl L. , Hofmockel Kirsten S.
Published: October 2021

Bioenergy crops are a promising energy alternative to fossil fuels. During bioenergy feedstock production, crop inputs shape the composition of soil microbial communities, which in turn influences nutrient cycling and plant productivity. In addition to cropping inputs, site characteristics (e.g., soil texture, climate) influence bacterial and fungal communities. We explored the response of soil microorganisms to bioenergy cropping system (switchgrass vs. maize) and site (sandy loam vs. silty loam) within two long-term experimental research stations. The live and total microbial community membership was investigated using 16S and ITS amplicon sequencing of soil RNA and DNA. For both nucleic acid types, we expected fungi and prokaryotes to be differentially impacted by crop and site due their dissimilar life strategies. We also expected live communities to be more strongly affected by site and crop than the total communities due to a sensitivity to recent stimuli. Instead, we found that prokaryotic and fungal community composition was primarily driven by site with a secondary crop effect, highlighting the importance of soil texture and fertility in shaping both communities. Specific highly abundant prokaryotic and fungal taxa within live communities were indicative of site and cropping systems, providing insight into treatment-specific, agriculturally relevant microbial taxa that were obscured within total community profiles. Within live prokaryote communities, predatory Myxobacteria spp. were largely indicative of silty and switchgrass communities. Within live fungal communities, Glomeromycota spp. were solely indicative of switchgrass soils, while a few very abundant Mortierellomycota spp. were indicative of silty soils. Site and cropping system had distinct effects on the live and total communities reflecting selection forces of plant inputs and environmental conditions over time. Comparisons between RNA and DNA communities uncovered live members obscured within the total community as well as members of the relic DNA pool. The associations between live communities and relic DNA are a product of the intimate relationship between the ephemeral responses of the live community and the accumulation of DNA within necromass that contributes to soil organic matter, and in turn shapes soil microbial dynamics.
Exogenous Citrulline and Glutamine Contribute to Reverse the Resistance of Salmonella to Apramycin
Authors: Yong Yan , Zhou Yanhong , Liu Kexin , Liu Guochang , Wu Liqin , Fang Binghu
Published: October 2021

Antibiotic resistance is an increasing concern for human and animal health worldwide. Recently, the concept of reverting bacterial resistance by changing the metabolic state of antibiotic-resistant bacteria has emerged. In this study, we investigated the reversal of Apramycin resistance in Salmonella. First, non-targeted metabonomics were used to identify key differential metabolites of drug-resistant bacteria. Then, the reversal effect of exogenous substances was verified in vivo and in vitro. Finally, the underlying mechanism was studied. The results showed that the metabolites citrulline and glutamine were significantly reduced in Apramycin-resistant Salmonella. When citrulline and glutamine were added to the culture medium of drug-resistant Salmonella, the killing effect of Apramycin was restored markedly. Mechanistic studies showed that citrulline and glutamine promoted the Tricarboxylic acid cycle, produced more NADH in the bacteria, and increased the proton-motive force, thus promoting Apramycin entry into the bacterial cells, and killing the drug-resistant bacteria. This study provides a useful method to manage infections by antibiotic-resistant bacteria.
Feasibility of Noninvasive Diagnosis of Spinal Vascular Diseases Using Time-Resolved Angiography With Stochastic Trajectories
Authors: Wei Xiao-Er , Li Ming-Hua , Qiao Rui-Hua , Yu Wei-Bin , Li Yue-Hua
Published: October 2021

Background and Purpose: To determine the feasibility of time-resolved angiography with stochastic trajectories (TWIST) in the diagnosis of spinal dural arteriovenous fistula (SDAVF) and perimedullary arteriovenous fistula (PAVF).

Methods: A total of 11 negative patients with TWIST examination were retrospective analyzed and then 18 patients with suspected spinal vascular diseases underwent TWIST. For negative patients, Adamkiewicz artery (AKA), great anterior radiculomedullary vein (GARV) and anterior spinal artery (ASA) were retrospective analyzed. In patients, the results of TWIST were compared with those of DSA.

Results: The displaying rates of the ASA, AKA and GARV in 11 negative patients were 100, 90.9, and 90.9%, respectively. The AKA and GARV were separated on TWIST. Of 18 patients, 11 and three were diagnosed with SDAVF and PAVF, respectively. The spinal cord vascular malformation diagnosed on TWIST was consistent with DSA with an excellent intermodality agreement (Kappa = 0.92, p < 0.001). The feeding artery and side of all 11 SDAVF patients were displayed on TWIST and the results were consistent with DSA. For PAVF patients, the feeding artery in two patients and the sides as displayed on TWIST were consistent with DSA.

Conclusions: TWIST enables the differentiation of the spinal artery and vein and the differential diagnosis of SDAVF and PAVF.
Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen
Authors: Cleypool Cindy G. J. , Brinkman David J. , Mackaaij Claire , Nikkels Peter G. J. , Nolte Martijn A. , Luyer Misha D. , de Jonge Wouter J. , Bleys Ronald L. A. W.
Published: October 2021

Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution.

Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10–25 and 25–70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures.

Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves.

Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients.
Parkinson's Disease Risk and Alcohol Intake: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies
Authors: Shao Chuan , Wang Xiaoya , Wang Pan , Tang Hui , He Jiaquan , Wu Nan
Published: October 2021

Background: The association between Parkinson's disease (PD) risk and alcohol intake is a controversial topic.

Objectives: To systematically assess the association between PD risk and alcohol intake.

Methods: PubMed and Embase databases were searched for eligible studies with prospective design on PD risk and alcohol intake. A meta-analysis with a random-effects model and dose-response analysis was performed. Relative risk ratios (RRs) with 95% CIs were calculated.

Results: Eleven prospective studies were included. Overall, a higher intake of alcohol was inversely associated with PD risk (RR: 0.81, 95% CI: 0.70–0.95, I2 = 73.7%). Significant differences existed between the specific types of alcoholic beverages and geographic area. Specifically, a significant association existed for beer (RR: 0.78, 95% CI: 0.65–0.94, I2 = 0.0%) and studies conducted in Asia (RR: 0.66, 95% CI: 0.55–0.80, I2 = 37.3%). Dose-response analysis indicated a nonlinear relationship between PD risk and alcohol exposure. No evidence for publication bias was detected.

Conclusions: In summary, our meta-analysis suggests that alcohol consumption was associated with a decreased risk of PD, with a nearly U-shaped association. Future studies are warranted to clarify the question of a specific type of alcoholic beverage-dependent association, geographic area effect, and possible threshold effects regarding both the adverse and beneficial effects of alcohol.
Millets Can Have a Major Impact on Improving Iron Status, Hemoglobin Level, and in Reducing Iron Deficiency Anemia–A Systematic Review and Meta-Analysis
Authors: Anitha Seetha , Kane-Potaka Joanna , Botha Rosemary , Givens D. Ian , Sulaiman Nur Liana Binti , Upadhyay Shweta , Vetriventhan Mani , Tsusaka Takuji W. , Parasannanavar Devraj J. , Longvah Thingnganing , Rajendran Ananthan , Subramaniam Kowsalya , Bhandari Raj Kumar
Published: October 2021

The prevalence of iron deficiency anemia is highest among low and middle-income countries. Millets, including sorghum, are a traditional staple in many of these countries and are known to be rich in iron. However, a wide variation in the iron composition of millets has been reported, which needs to be understood in consonance with its bioavailability and roles in reducing anemia. This systematic review and meta-analysis were carried out to analyze the scientific evidence on the bioavailability of iron in different types of millets, processing, and the impact of millet-based food on iron status and anemia. The results indicated that iron levels in the millets used to study iron bioavailability (both in vivo and in vitro) and efficacy varied with the type and variety from 2 mg/100 g to 8 mg/100 g. However, not all the efficacy studies indicated the iron levels in the millets. There were 30 research studies, including 22 human interventions and 8 in vitro studies, included in the meta-analysis which all discussed various outcomes such as hemoglobin level, serum ferritin level, and absorbed iron. The studies included finger millet, pearl millet, teff and sorghum, or a mixture of millets. The results of 19 studies conducted on anaemic individuals showed that there was a significant (p < 0.01) increase in hemoglobin levels by 13.2% following regular consumption (21 days to 4.5 years) of millets either as a meal or drink compared with regular diets where there was only 2.7% increase. Seven studies on adolescents showed increases in hemoglobin levels from 10.8 ± 1.4 (moderate anemia) to 12.2 ± 1.5 g/dl (normal). Two studies conducted on humans demonstrated that consumption of a pearl millet-based meal significantly increased the bioavailable iron (p < 0.01), with the percentage of bioavailability being 7.5 ± 1.6, and provided bioavailable iron of 1 ± 0.4 mg. Four studies conducted on humans showed significant increases in ferritin level (p < 0.05) up to 54.7%. Eight in-vitro studies showed that traditional processing methods such as fermentation and germination can improve bioavailable iron significantly (p < 0.01) by 3.4 and 2.2 times and contributed to 143 and 95% of the physiological requirement of women, respectively. Overall, this study showed that millets can reduce iron deficiency anemia.
US Older Adults That Consume Avocado or Guacamole Have Better Cognition Than Non-consumers: National Health and Nutrition Examination Survey 2011–2014
Authors: Cheng Feon W. , Ford Nikki A. , Taylor Matthew K.
Published: October 2021

Purpose: The goal of this study is to examine how avocado relates to cognitive function among older adults.

Methods: A total of 2,886 National Health and Nutrition Examination Survey 2011–2014 participants aged 60 or older met the eligibility criteria and were included of our cross-sectional study. Participants were binarily classified as avocado consumers (i.e., reported consuming any avocado/guacamole in either 24-h dietary recalls) or non-consumers. Cognitive performance was evaluated with: Consortium to Establish a Registry for Alzheimer's disease (CERAD)—immediate and delayed recall (IWR/DWR), the Animal Fluency test, and the Digit Symbol Substitution Test. We calculated the education-dependent z-scores for each subject because education level can impact cognitive function. Global cognitive score, an average of the z-scores for each cognitive test, was calculated in participants who had completed all four tests. To account for relevant covariates, we tested for mean differences in cognition between consumers and non-consumers using independent sample t-tests and ANCOVA, special cases of ordinary least squares regression.

Results: Avocado consumers had significantly better cognitive scores across all cognitive tests and the global cognition score (p < 0.05) in the unadjusted model. Some mean differences attenuated after adjusting for potential confounders, but others remained significant. Compared to non-consumers, avocado consumers had significantly higher z-scores of 0.15, 0.15, and 0.11 for CERAD IWR and DWR, and global cognition score, respectively (all p < 0.05 in adjusted models).

Conclusion: Avocado consumption was associated with significantly better IWR, DWR, and the overall global cognition score, which remained significant when controlling for all relevant confounders.
Lactobacillus plantarum ZJUFB2 Prevents High Fat Diet-Induced Insulin Resistance in Association With Modulation of the Gut Microbiota
Authors: Zhong Hao , Wang Jian , Abdullah  , Hafeez Muhammad Adnan , Guan Rongfa , Feng Fengqin
Published: October 2021

Lactobacillus plantarum ZJUFB2 is a novel probiotic isolate derived from Chinese traditional sourdough that possesses promising probiotics properties. This study aimed to investigate the effects of L. plantarum ZJUFB2 (B2) on insulin sensitivity using mice fed on a high-fat diet (HFD) as well as to explore the involved mechanisms. Purposely, male C57BL/6 mice continuously received an intervention of B2 (~109 CFU/day) for 16 weeks. The results showed that B2 treatment remarkably ameliorated insulin resistance and hyperglycemia in HFD-fed mice. The B2 intervention significantly decreased the hepatic lipid accumulation, serum low-density lipoproteins cholesterol, and lipopolysaccharides, and regulated the bile acids levels as well as liver mRNA expression involved in lipid metabolism. Moreover, the B2 intervention significantly changed the gut microbiota, specifically, showed a lower abundance of obesity-related and inflammation-associated microbes, e.g., Ruminococcus and Mogibacteriaceae. Furthermore, it exhibited a higher abundance of short-chain fatty acids and bile salt hydrolas-producing bacteria, such as Bifidobacterium and F16 compared with the HFD group. The findings of this study suggested that B2 is a novel probiotic, effective in preventing insulin resistance by improving the gut microbiota and bile acids.
Reassessing the Value of Contrast-Enhanced Ultrasonography in Differential Diagnosis of Cervical Tuberculous Lymphadenitis and Lymph Node Metastasis of Papillary Thyroid Carcinoma
Authors: Zhang Xu , Wang Lingling , Feng Na , Ni Tu , Tang Wei
Published: October 2021

Aim

We aimed to evaluate the ability of contrast-enhanced ultrasonography (CEUS) to perform differential diagnosis of cervical tuberculous lymphadenitis and lymph node metastasis from papillary thyroid cancer (PTC).

Methods

We analyzed 102 enlarged cervical lymph nodes as diagnosed by conventional ultrasound (US) and CEUS. The US and CEUS enhancement pattern and the time intensity curve (TIC) of the metastatic lymph nodes or tuberculous lymph nodes were compared following standard pathological protocols. The TIC included peak time (TTP), peak intensity (PI), and area under the gamma curve (AUC).

Results

Pathological results demonstrated that 48 out of the 102 enlarged lymph nodes were lymph node metastasis from PTC, while 54 were tuberculous lymphadenitis. There was statistically significant differences in hyperechoic islands, pulse-like enhancement, and asynchronous enhancement between tuberculous lymphadenitis and lymph node metastasis (P < 0.05), but their diagnostic sensitivity and specificity were unsatisfactory. In addition, our data did not show statistically significant difference in enhancement direction, enlarged range on CEUS, and perfusion defect (P > 0.05). Similarly, quantitative parameters such as PI, TTP, and AUC did not yield significant differences between the groups.

Conclusion

Taken together, the present results demonstrate that CEUS can provide valuable information on lymph node blood flow, which can be used to identify tuberculous lymphadenitis and lymph node metastasis of PTC.
A Systematic Review and Meta-Analysis of Male Infertility and the Subsequent Risk of Cancer
Authors: Behboudi-Gandevani Samira , Bidhendi-Yarandi Razieh , Panahi Mohammad Hossein , Vaismoradi Mojtaba
Published: October 2021

Objectives

The primary objective of this systemic review and meta-analysis was to investigate the risk of developing composite outcome of all cancers, regardless of the type of cancer among men with infertility diagnosis compared to fertile counterparts. The secondary objective was to compare the pooled risk of developing individual specific cancers between two groups.

Methods

A systematic literature search was performed on the databases of PubMed (including Medline), Scopus, and Web of Science to retrieve observational studies published in English language from 01.01.1990 to 28. 02. 2021. They assessed cancer events in males with an infertility diagnosis compared to controls without infertility. The outcomes of interest were a composite outcome of cancers including all known cancer types, and also specific individual cancers. The fixed/random effects model was used to analyze heterogeneous and non-heterogeneous results. Publication bias was assessed using the Harbord test, Egger test, Begg test, and funnel plot. The pooled odds ratio of cancers was calculated using the DerSimonian and Laird, and inverse variance methods. Studies’ quality and risk of bias were assessed using structured standard tools.

Results

We included eight cohort studies involving 168,327 men with the diagnosis of infertility and 2,252,806 men without it. The total number of composite outcome of cancers as well as individual cancers including prostate, testicular and melanoma were 1551, 324, 183 and 121 in the infertile men and 12164, 3875, 849, and 450 in the fertile men, respectively. The pooled OR of the composite outcome of cancers, regardless of the type of cancer, in men with infertility was 1.4 folds higher than those without infertility (pooled OR = 1.43, 95% confidence interval [CI]: 1.25-1.64). Meta-analysis of individual cancers including prostate, testicular and melanoma between two groups was carried out. The pooled ORs of testicular and prostate cancers in men with the diagnosis of infertility were significantly higher than controls without infertility (pooled OR = 1.91, 95% CI: 1.52-2.42 and pooled OR = 1.48, 95% CI: 1.05-2.08, respectively). Additionally, the pooled OR of melanoma in men with infertility was 1.3 folds higher than those without infertility (pooled OR = 1.31, 95% CI: 1.06-1.62).

Conclusion

A greater risk of cancers in men with male infertility was found suggesting that the history of male infertility might be an important risk factor for developing cancers in later life. Further well-designed long-term population-based prospective studies, considering all known cancers and their accompanying risk factors should be conducted to support our findings.
Diagnostic Value of CT- and MRI-Based Texture Analysis and Imaging Findings for Grading Cartilaginous Tumors in Long Bones
Authors: Deng Xue-Ying , Chen Hai-Yan , Yu Jie-Ni , Zhu Xiu-Liang , Chen Jie-Yu , Shao Guo-Liang , Yu Ri-Sheng
Published: October 2021

Objective

To confirm the diagnostic performance of computed tomography (CT)-based texture analysis (CTTA) and magnetic resonance imaging (MRI)-based texture analysis for grading cartilaginous tumors in long bones and to compare these findings to radiological features.

Materials and Methods

Twenty-nine patients with enchondromas, 20 with low-grade chondrosarcomas and 16 with high-grade chondrosarcomas were included retrospectively. Clinical and radiological information and 9 histogram features extracted from CT, T1WI, and T2WI were evaluated. Binary logistic regression analysis was performed to determine predictive factors for grading cartilaginous tumors and to establish diagnostic models. Another 26 patients were included to validate each model. Receiver operating characteristic (ROC) curves were generated, and accuracy rate, sensitivity, specificity and positive/negative predictive values (PPV/NPV) were calculated.

Results

On imaging, endosteal scalloping, cortical destruction and calcification shape were predictive for grading cartilaginous tumors. For texture analysis, variance, mean, perc.01%, perc.10%, perc.99% and kurtosis were extracted after multivariate analysis. To differentiate benign cartilaginous tumors from low-grade chondrosarcomas, the imaging features model reached the highest accuracy rate (83.7%) and AUC (0.841), with a sensitivity of 75% and specificity of 93.1%. The CTTA feature model best distinguished low-grade and high-grade chondrosarcomas, with accuracies of 71.9%, and 80% in the training and validation groups, respectively; T1-TA and T2-TA could not distinguish them well. We found that the imaging feature model best differentiated benign and malignant cartilaginous tumors, with an accuracy rate of 89.2%, followed by the T1-TA feature model (80.4%).

Conclusions

The imaging feature model and CTTA- or MRI-based texture analysis have the potential to differentiate cartilaginous tumors in long bones by grade. MRI-based texture analysis failed to grade chondrosarcomas.
The Value of Predicting Human Epidermal Growth Factor Receptor 2 Status in Adenocarcinoma of the Esophagogastric Junction on CT-Based Radiomics Nomogram
Authors: Wang Shuxing , Chen Yiqing , Zhang Han , Liang Zhiping , Bu Jun
Published: October 2021

Purpose

We developed and validated a CT-based radiomics nomogram to predict HER2 status in patients with adenocarcinoma of esophagogastric junction (AEG).

Method

A total of 101 patients with HER2-positive (n=46) and HER2-negative (n=55) esophagogastric junction adenocarcinoma (AEG) were retrospectively analyzed. They were then randomly divided into a training cohort (n=70) and a verification cohort (n=31). The radiomics features were obtained from the portal phase of the CT enhanced scan. We used the least absolute shrinkage and selection operator (LASSO) logistic regression method to select the best radiomics features in the training cohort, combined them linearly, and used the radiomics signature formula to calculate the radiomics score (Rad-score) of each AEG patient. A multivariable logistic regression method was applied to develop a prediction model that incorporated the radiomics signature and independent risk predictors. The prediction performance of the nomogram was evaluated using the training and validation cohorts.

Result

In the training (P<0.001) and verification groups (P<0.001), the radiomics signature combined with seven radiomics features was significantly correlated with HER2 status. The nomogram composed of CT-reported T stage and radiomics signature showed very good predictive performance for HER2 status. The area under the curve (AUC) of the training cohort was 0.946 (95% CI: 0.919–0.973), and that of the validation group was 0.903 (95% CI: 0.847–0.959). The calibration curve of the radiomics nomogram showed a good degree of calibration. Decision-curve analysis revealed that the radiomics nomogram was useful.

Conclusion

The nomogram CT-based radiomics signature combined with CT-reported T stage can better predict the HER2 status of AEG before surgery. It can be used as a non-invasive prediction tool for HER2 status and is expected to guide clinical treatment decisions in clinical practice, and it can assist in the formulation of individualized treatment plans.
Case Report: Effective Treatment With Pyrotinib and Capecitabine in a Heavily Pretreated Locally Advanced Breast Cancer Harboring Both HER2 Overexpression and Mutant
Authors: Gao Zhichao , Xu Junnan , Wang Yan , Wu Jie , Sun Tao
Published: October 2021

The prognosis for female patients with locally advanced breast cancer (LABC) has improved with the emergence of novel drugs, especially for those who have HER2 overexpression or ERBB-2 amplification. Trastuzumab-based regimen has been the paradigm in guidelines as first-line therapy, whereas many patients got progressive disease after several cycles of treatment or rapidly progress because of primary resistance. Point mutations of ERBB2 gene occur in both HER2-amplication and non-amplification patients, with a 2% ratio in HER2 non-amplification cohort and 1.48% in HER2 amplication population. The acquired mutation ratio of ERBB2 substantially raised to 16.7%–17.7% in patients prior to trastuzumab treatment. ERBB2 mutation may be a critical reason of resistance and disease progression among the patients treated with anti-HER2 monoclonal trastuzumab or dual anti-HER2 antibodies with trastuzumab and pertuzumab, or tyrosine-kinase inhibitor. ERBB-2 mutation with L755S and V842I indicates resistance to trastuzumab, while that with L755S and K753I indicates resistance to lapatinib; these mutations maybe sensitive to pan-HER tyrosine-kinase inhibitors. A 48-year woman diagnosed with HER2-positive LABC developed trastuzumab resistance after three lines of trastuzumab cross-line treatment with partial response (PR) as the best response. The tissue was performed by next-generation sequencing (NGS), and the results discovered L755S in ERBB2 gene. Then, she received effective treatment with pyrotinib plus capecitabine and underwent mastectomy after six cycles of combined treatment with PR. Subsequently, breast mastectomy was performed, and she took pyrotinib plus capecitabine for 1 year and pyrotinib monotherapy for another 1 year as adjuvant therapy and achieved a long-term clinical benefit. In conclusion, pyrotinib is a potential neoadjuvant agent for patients who are heavily pretreated and harbor both ERBB2 amplification and ERBB2 mutant in locally advanced breast cancer.
Computed Tomography-Based Radiomics in Predicting T Stage and Length of Esophageal Squamous Cell Carcinoma
Authors: Yang Mingwei , Hu Panpan , Li Minglun , Ding Rui , Wang Yichun , Pan Shuhao , Kang Mei , Kong Weihao , Du Dandan , Wang Fan
Published: October 2021

Background

Because of the superficial and infiltrative spreading patterns of esophageal squamous cell carcinoma (ESCC), an accurate assessment of tumor extent is challenging using imaging-based clinical staging. Radiomics features extracted from pretreatment computed tomography (CT) or magnetic resonance imaging have shown promise in identifying tumor characteristics. Accurate staging is essential for planning cancer treatment, especially for deciding whether to offer surgery or radiotherapy (chemotherapy) in patients with locally advanced ESCC. Thus, this study aimed to evaluate the predictive potential of contrast-enhanced CT-based radiomics as a non-invasive approach for estimating pathological tumor extent in ESCC patients.

Methods

Patients who underwent esophagectomy between October 2011 and September 2017 were retrospectively studied and included 116 patients with pathologically confirmed ESCC. Contrast-enhanced CT from the neck to the abdomen was performed in all patients during the 2 weeks before the operation. Radiomics features were extracted from segmentations, which were contoured by radiologists. Cluster analysis was performed to obtain clusters with similar radiomics characteristics, and chi-squared tests were used to assess differences in clinicopathological features and survival among clusters. Furthermore, a least absolute shrinkage and selection operator was performed to select radiomics features and construct a radiomics model. Receiver operating characteristic analysis was used to evaluate the predictive ability of the radiomics signatures.

Results

All 116 ESCC patients were divided into two groups according to the cluster analysis. The chi-squared test showed that cluster-based radiomics features were significantly correlated with T stage (p = 0.0254) and tumor length (p = 0.0002). Furthermore, CT radiomics signatures exhibited favorable predictive performance for T stage (area under the curve [AUC] = 0.86, sensitivity = 0.77, and specificity = 0.87) and tumor length (AUC = 0.95, sensitivity = 0.92, and specificity = 0.91).

Conclusions

CT contrast radiomics is a simple and non-invasive method that shows promise for predicting pathological T stage and tumor length preoperatively in ESCC patients and may aid in the accurate assessments of patients in combination with the existing examinations.
Differences in Cancer Death Risk Long After ACS Among Selected Urban and Rural Areas in North Italy: The ABC-7a† Study on Heart Disease
Authors: Mahmoud Heba T. , Berton Giuseppe , Cordiano Rocco , Palmieri Rosa , Nardi Tobia , Abdel-Wahab Mohammad AK , Cavuto Fiorella
Published: October 2021

Background

An increased risk of cancer death has been demonstrated for patients diagnosed with acute coronary syndrome (ACS). We are investigating possible geographic risk disparities.

Methods

This prospective study included 541 ACS patients who were admitted to hospitals and discharged alive in three provinces of Italy’s Veneto region. The patients were classified as residing in urban or rural areas in each province.

Results

With 3 exceptions, all patients completed the 22-year follow-up or were followed until death. Urban (46%) and rural (54%) residents shared most of their baseline demographic and clinical characteristics. Pre-existing malignancy was noted in 15 patients, whereas 106 patients developed cancer during the follow-up period, which represented 6232 person-years. No difference in the cancer death risk was found between the urban and rural areas or between southern and northern provinces (hazard ratio [HR] 1.1; 95% confidence interval [CI] 0.7–1.7; p = 0.59 and HR 1.1; 95% CI 0.9–1.4; p = 0.29, respectively) according to the unadjusted Cox regression analysis. Geographic areas, however, showed a strong positive interaction, with risk increasing from the urban to rural areas from southern to northern provinces (HR 1.9; 95% CI 1.1–3.0; p = 0.01). The fully adjusted Cox regression and Fine-Gray competing risk regression models provided similar results. Interestingly, these results persisted, and even strengthened, after exclusion of the 22 patients who developed malignancy and survived to the end of follow-up. We did not observe an urban/rural difference in non-neoplastic death risk or a significant interaction between the geographic areas.

Conclusion

Our analysis reveals that the cancer death risk among unselected ACS patients in Italy’s Veneto region significantly differs by geography. The northern rural area has the highest risk. These results highlight the importance of implementing a preventive policy based on area-specific knowledge.