Publications by authors named "Zhuo Li"

1,010 Publications

  • Page 1 of 1

Identification of misdiagnosis by deep neural networks on a histopathologic review of breast cancer lymph node metastases.

Sci Rep 2022 Aug 5;12(1):13482. Epub 2022 Aug 5.

Digital Health China Technologies Corporation Limited, Beijing, 100080, China.

The frozen section (FS) diagnoses of pathology experts are used in China to determine whether sentinel lymph nodes of breast cancer have metastasis during operation. Direct implementation of a deep neural network (DNN) in clinical practice may be hindered by misdiagnosis of the algorithm, which affects a patient's treatment decision. In this study, we first obtained the prediction result of the commonly used patch-DNN, then we present a relative risk classification and regression tree (RRCART) to identify the misdiagnosed whole-slide images (WSIs) and recommend them to be reviewed by pathologists. Applying this framework to 2362 WSIs of breast cancer lymph node metastasis, test on frozen section results in the mean area under the curve (AUC) reached 0.9851. However, the mean misdiagnosis rate (0.0248), was significantly higher than the pathologists' misdiagnosis rate (p < 0.01). The RRCART distinguished more than 80% of the WSIs as a high-accuracy group with an average accuracy reached to 0.995, but the difference with the pathologists' performance was not significant (p > 0.01). However, the other low-accuracy group included most of the misdiagnoses of DNN models. Our research shows that the misdiagnosis from deep learning model can be further enriched by our method, and that the low-accuracy WSIs must be selected for pathologists to review and the high-accuracy ones may be ready for pathologists to give diagnostic reports.
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http://dx.doi.org/10.1038/s41598-022-17606-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355979PMC
August 2022

Ingredient-Guided Region Discovery and Relationship Modeling for Food Category-Ingredient Prediction.

IEEE Trans Image Process 2022 4;31:5214-5226. Epub 2022 Aug 4.

Recognizing the category and its ingredient composition from food images facilitates automatic nutrition estimation, which is crucial to various health relevant applications, such as nutrition intake management and healthy diet recommendation. Since food is composed of ingredients, discovering ingredient-relevant visual regions can help identify its corresponding category and ingredients. Furthermore, various ingredient relationships like co-occurrence and exclusion are also critical for this task. For that, we propose an ingredient-oriented multi-task food category-ingredient joint learning framework for simultaneous food recognition and ingredient prediction. This framework mainly involves learning an ingredient dictionary for ingredient-relevant visual region discovery and building an ingredient-based semantic-visual graph for ingredient relationship modeling. To obtain ingredient-relevant visual regions, we build an ingredient dictionary to capture multiple ingredient regions and obtain the corresponding assignment map, and then pool the region features belonging to the same ingredient to identify the ingredients more accurately and meanwhile improve the classification performance. For ingredient-relationship modeling, we utilize the visual ingredient representations as nodes and the semantic similarity between ingredient embeddings as edges to construct an ingredient graph, and then learn their relationships via the graph convolutional network to make label embeddings and visual features interact with each other to improve the performance. Finally, fused features from both ingredient-oriented region features and ingredient-relationship features are used in the following multi-task category-ingredient joint learning. Extensive evaluation on three popular benchmark datasets (ETH Food-101, Vireo Food-172 and ISIA Food-200) demonstrates the effectiveness of our method. Further visualization of ingredient assignment maps and attention maps also shows the superiority of our method.
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http://dx.doi.org/10.1109/TIP.2022.3193763DOI Listing
August 2022

The association of endosalpingiosis with gynecologic malignancy.

Gynecol Oncol 2022 Jul 28. Epub 2022 Jul 28.

Department of Medical and Surgical Gynecology, Mayo Clinic, Jacksonville, FL, United States of America. Electronic address:

Objective: Endosalpingiosis is a poorly understood condition of ectopic epithelium resembling the fallopian tubes. It has been described as an incidental pathology finding, a disease similar to endometriosis, and in association with malignancy. The objective of this study is to determine if endosalpingiosis (ES) has an increased association with gynecologic malignancy when compared to endometriosis (EM).

Methods: This is a retrospective case-control analysis of patients with a histologic diagnosis of endosalpingiosis or endometriosis at three affiliated academic hospitals between 2000 and 2020. All ES patients were included, and 1:1 matching was attempted to obtain a comparable cohort of EM patients. Demographic and clinical data were obtained, and statistical analysis was performed.

Results: A total of 967 patients (515 ES and 452 EM) were included. ES patients were significantly older than EM patients (median age 52 vs 48 years, p < 0.001). The ES group had significantly more cancer diagnoses at surgery than the EM group (40.1% vs 18.1%, p < 0.001); this difference persisted in a sub-analysis excluding patients with known or suspected malignancy (20.9% vs 5.6%, p < 0.001). ES patients had lower overall survival (10-year freedom from death: 77.0% vs 90.5%, p < 0.001). After adjusting for confounders, multivariable analysis showed that ES patients had increased cancer diagnosed at surgery (OR = 2.48, p < 0.001) and greater risk of death (OR = 1.69, p = 0.017).

Conclusions: Endosalpingiosis was found concurrently with malignancy in 40% of cases, and this effect was preserved in multi-variable and sub-group analyses. Further research consisting of longer follow-up and exploration of molecular relationships between ES and cancer are forthcoming.
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http://dx.doi.org/10.1016/j.ygyno.2022.07.025DOI Listing
July 2022

Urbanization and cognitive function among middle-aged and old adults in China.

J Gerontol B Psychol Sci Soc Sci 2022 Jul 31. Epub 2022 Jul 31.

Department of Global Health, School of Public Health, Peking University, China.

Objectives: Our study examined the effect of urbanization on cognitive function and its possible pathways among Chinese middle-aged and older adults independent of the influence of health-selective migration.

Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we compared cognitive function among three groups (urbanized rural residents, rural non-migrants and urban non-migrants). Logistic regression and structural equation models were applied to explore the impact of urbanization on cognitive function and the potential mechanisms.

Results: Compared with the urbanized-rural group, urban non-migrants had better cognitive function, with a significant coefficient of 1.56 (95% CI: 1.22,1.89) for global cognition scores and 0.37 (95% CI: 0.22,0.53) for episodic memory scores. The rural non-migrants had the worst cognitive function (β=-0.79, 95% CI: -1.04, -0.55) and lower scores of mental intactness (β=-0.65, 95% CI: -0.84, -0.57) and episodic memory (β=-0.14, 95% CI: -0.26, -0.03). The association between urbanization and cognitive function was mainly mediated by income and living conditions among middle-aged and older adults.

Discussion: Rural people who experienced planned urbanization in China had higher cognitive scores than rural non-migrants. Urbanization could thus have a beneficial and cumulative effect on cognitive function. Improvements in living conditions and changes in income are the main drivers behind the relationship. However, urbanization could compensate for the negative impact on cognitive function from disadvantaged early life conditions, but it cannot completely eliminate the gap between urbanized rural people and urban non-migrants.
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http://dx.doi.org/10.1093/geronb/gbac102DOI Listing
July 2022

A land-use benefit evaluation system with case study verification.

PLoS One 2022 29;17(7):e0271557. Epub 2022 Jul 29.

Ministry of Ecology and Environment Center for Satellite Application on Ecology and Environment, Beijing, China.

In regional land-use planning, many different demands for often-limited land resources must be weighed against each other. Analysis of the benefits of different land-use types is of great significance in land-use design. However, a good evaluation methodology does not exist. To facilitate a comparative analysis of land-use benefits, this paper presents an evaluation system consisting of four steps: (1) Connotation dissection to determine the land-use benefits, (2) construction of a land-use benefit classification system to summarize a limited number of land-use benefit types by an inductive method, (3) land-use benefit valuation, which includes a biophysical model, direct and indirect market valuations, and The Economics of Ecosystems and Biodiversity value conversion method, and (4) case analysis of the evaluation results according to local conditions. Empirical results from a case study of Mentougou District, Beijing, China, show that (i) the evaluation results of land-use benefit groups provides information on each land-use type and the spatial distribution of land-use benefits in Mentougou District, (ii) the topography of Mentougou District has an important influence on economic and ecological land-use benefits, and (iii) there is a synergistic effect of economic and social land-use benefits.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271557PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337706PMC
August 2022

A geometric alignment for human temporal bone CT images via lateral semicircular canals segmentation.

Med Phys 2022 Jul 29. Epub 2022 Jul 29.

Faculty of Information Technology, Beijing University of Technology, Beijing, 100124, China.

Purpose: Due to the different posture of the subject and settings of CT scanners, the CT images of the human temporal bone should be geometrically aligned with multi-planar reconstruction to ensure the symmetry of the bilateral anatomical structure. Manual alignment is a time-consuming task for radiologists and an important pre-processing step for further computer-aided CT analysis. We propose a fully automatic alignment algorithm for temporal bone CT images via Lateral Semicircular Canals (LSCs) segmentation.

Methods: The LSCs are segmented with our proposed multi-feature fusion network as anchors at first. Then, we define a standard 3D coordinate system and propose an alignment procedure.

Results: The experimental results show that our LSC segmentation network achieved a higher segmentation accuracy. The acceptable rate is achieved 85% over 910 raw temporal bone CT sequences. The alignment speed is reduced from 10 minutes by manual to 60s.

Conclusions: Aiming at the problem of bilateral asymmetry in the raw temporal bone CT images, we propose an automatic geometric alignment method. Our proposed method can help to perform alignment of temporal bone CT images efficiently. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mp.15889DOI Listing
July 2022

Association of Plasma and Electroencephalography Markers With Motor Subtypes of Parkinson's Disease.

Front Aging Neurosci 2022 12;14:911221. Epub 2022 Jul 12.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

Objective: The aim of this study was to investigate the correlations of plasma neurodegenerative proteins and electroencephalography (EEG) dynamic functional network (DFN) parameters with disease progression in early Parkinson's disease (PD) with different motor subtypes, including tremor-dominant (TD) and postural instability and gait disorder (PIGD).

Methods: In our study, 33 patients with PD (21 TD and 12 PIGD) and 33 healthy controls (HCs) were enrolled. Plasma neurofilament light chain (NfL), α-synuclein (α-syn), total-tau (t-tau), β-amyloid 42 (Aβ42), and β-amyloid 40 (Aβ40) levels were measured using an ultrasensitive single-molecule array (Simoa) immunoassay. All the patients with PD underwent EEG quantified by DFN analysis. The motor and non-motor performances were evaluated by a series of clinical assessments. Subsequently, a correlation analysis of plasma biomarkers and EEG measures with clinical scales was conducted.

Results: In the TD group, plasma NfL exhibited a significant association with MDS-UPDRS III and Montreal Cognitive Assessment (MoCA). A higher Aβ42/40 level was significantly related to a decrease in Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) in the PIGD group. In terms of the correlation between EEG characteristic parameters and clinical outcomes, trapping time () delta was positively correlated with MDS-UPDRS III and MoCA scores in the TD group, especially in the prefrontal and frontal regions. For other non-motor symptoms, there were significant direct associations of theta with HAMD and HAMA, especially in the prefrontal region, and gamma was particularly correlated with Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores in the prefrontal, frontal, and parietal regions in the TD group. Furthermore, there was a significant positive correlation between plasma t-tau and , and pairwise correlations were found among plasma NfL, theta , and MoCA scores in the TD group.

Conclusion: These results provide evidence that plasma neurodegenerative proteins and EEG measures have great potential in predicting the disease progression of PD subtypes, especially for the TD subtype. A combination of these two kinds of markers may have a superposition effect on monitoring and estimating the prognosis of PD subtypes and deserves further research in larger, follow-up PD cohorts.
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http://dx.doi.org/10.3389/fnagi.2022.911221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314775PMC
July 2022

Structure of Randomly Distributed Nanochain Aggregates on Silicon Substrates: Modeling and Optical Absorption Characteristics.

Materials (Basel) 2022 Jul 7;15(14). Epub 2022 Jul 7.

School of Optics and Photonics, Beijing Institute of Technology, Zhongguancun South Street 5, Beijing 100081, China.

Nanoparticle aggregate structures allow for efficient photon capture, and thus exhibit excellent optical absorption properties. In this study, a model of randomly distributed nanochain aggregates on silicon substrates is developed and analyzed. The Gaussian, uniform, and Cauchy spatial distribution functions are used to characterize the aggregate forms of the nanochains and their morphologies are realistically reconstructed. The relationships between the structural parameters (thickness and filling factor), equivalent physical parameters (density, heat capacity, and thermal conductivity), and visible absorptivity of the structures are established and analyzed. All the above-mentioned parameters exhibit extreme values, which maximize the visible-range absorption; these values are determined by the material properties and nanochain aggregate structure. Finally, Al nanochain aggregate samples are fabricated on Si substrates by reducing the kinetic energy of the metal vapor during deposition. The spectral reflection characteristics of the samples are studied experimentally. The Spearman correlation coefficients for the calculated spectral absorption curves and those measured experimentally are higher than 0.82, thus confirming that the model is accurate. The relative errors between the calculated visible-range absorptivities and the measured data are less than 0.3%, further confirming the accuracy of the model.
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http://dx.doi.org/10.3390/ma15144778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325106PMC
July 2022

Targeted-Deletion of a Tiny Sequence via Prime Editing to Restore SMN Expression.

Int J Mol Sci 2022 Jul 19;23(14). Epub 2022 Jul 19.

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China.

Spinal muscular atrophy (SMA) is a devastating autosomal recessive motor neuron disease associated with mutations in the survival motor neuron 1 () gene, the leading genetic cause of infant mortality. A nearly identical copy gene () is retained in almost all patients with SMA. However, fails to prevent disease development because of its alternative splicing, leading to a lack of exon 7 in the majority of transcripts and yielding an unstable truncated protein. Several splicing regulatory elements, including intronic splicing silencer-N1 (ISS-N1) of have been described. In this study, targeted-deletion of ISS-N1 was achieved using prime editing (PE) in SMA patient-specific induced pluripotent stem cells (SMA-iPSCs) with a high efficiency of 7/24. FL-SMN expression was restored in the targeted-deletion iPS clones and their derived motor neurons (iMNs). Notably, the apoptosis of the iMNs, caused by the loss of SMN protein that leads to the hyperactivity of endoplasmic reticulum (ER) stress, was alleviated in targeted-deletion iPSCs derived-iMNs. Thus, this is the first study to demonstrate that the targeted-deletion of ISS-N1 via PE for restoring FL-SMN expression holds therapeutic promise for SMA.
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http://dx.doi.org/10.3390/ijms23147941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317564PMC
July 2022

Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice.

Nat Commun 2022 Jul 22;13(1):4255. Epub 2022 Jul 22.

Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.

CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin. Camk4-deficient (Camk4) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice. There are more macrophages and fewer IL-17Aγδ TCR cells in the skin of IMQ-treated Camk4 mice compared to IMQ-treated WT mice. CaMK4 inhibits IL-10 production by macrophages, thus allowing excessive psoriatic inflammation. Deletion of Camk4 in macrophages alleviates IMQ-induced psoriatic inflammation in mice. In keratinocytes, CaMK4 inhibits apoptosis as well as promotes cell proliferation and the expression of pro-inflammatory genes such as S100A8 and CAMP. Taken together, these data indicate that CaMK4 regulates IMQ-induced psoriasis by sustaining inflammation and provides a potential target for psoriasis treatment.
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http://dx.doi.org/10.1038/s41467-022-31935-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307837PMC
July 2022

Fluorescence fingerprinting characteristics of water-soluble organic carbon from size-resolved particles during pollution event.

Chemosphere 2022 Jul 18;307(Pt 1):135748. Epub 2022 Jul 18.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150090, China; School of Environment, Harbin Institute of Technology, Harbin, 150090, China. Electronic address:

A typical haze pollution process in northern China has necessitated this study which focuses on the fluorescence characteristics of water-soluble organic carbon (WSOC) in size-resolved particles. High concentrations of WSOC were found in both fine (38 μg/m³) and coarse particles (36 μg/m³) during the pollution period, which may be related to the secondary formation of organic aerosols and stable meteorological conditions. Five fluorescent components in WSOC were extracted by parallel factor analysis. Our results showed that the fluorophores in fine and coarse particles were mainly humic-like substances (humic-like, terrestrial humic-like, and high oxidation humic-like substances) and protein-like substances (protein-like and tyrosine-like substances), respectively. Moreover, the aging degree analysis, pollution source tracing, and concentration prediction of WSOC were carried out by fluorescence index. An innovative technique called self-organizing map was proposed for an in-depth investigation of the contamination mechanism of the atmospheric organic aerosol. Furthermore, the difference in the fluorescence characteristics of WSOC in fine particles was higher than that in coarse particles. The atmospheric pollution process increased the degree of difference in fluorescence characteristics. Additionally, an effective method for predicting the size of atmospheric particles was established by combining excitation-emission matrix fluorescence spectroscopy with classification and regression tree analysis.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135748DOI Listing
July 2022

Relationship between Vancomycin Trough Serum Concentrations and Clinical Outcomes in Children: a Systematic Review and Meta-Analysis.

Antimicrob Agents Chemother 2022 Jul 13:e0013822. Epub 2022 Jul 13.

Department of Pharmacy, Shaanxi Provincial People's Hospital, Xi'an, China.

To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021. All studies were screened and evaluated using the Cochrane systematic review method. Then, the feature information was extracted for meta-analysis. The evaluated results included clinical efficacy, vancomycin-associated nephrotoxicity, hepatotoxicity, ototoxicity, mortality, and microbial clearance. A total of 35 studies involving 4820 children were included in the analysis. The meta-analysis showed that compared with children with vancomycin trough concentrations <10 μg/mL, those with vancomycin trough concentrations ≥10 μg/mL had a higher clinical efficacy rate [OR: 2.23, 95% CI: 1.29 to 3.84, = 0.004] and higher incidences of nephrotoxicity [OR: 2.76, 95% CI: 1.51 to 5.07, = 0.001], ototoxicity [OR: 1.87, 95% CI: 1.08 to 3.23, = 0.02] and microbial clearance [OR: 2.36, 95% CI: 1.53 to 3.64, = 0.0001]. All-cause mortality [OR: 1.07, 95% CI: 0.45 to 2.53, = 0.88] and hepatotoxicity [OR: 0.84, 95% CI: 0.46 to 1.53, = 0.57] were similar between the two groups. Subgroup analysis showed that compared with children with vancomycin trough concentrations of 10 to 15 μg/mL, those with vancomycin trough concentrations >15 μg/mL had a higher incidence of nephrotoxicity [OR: 2.64, 95% CI: 1.28 to 5.43, = 0.008], but there was no significant difference in clinical efficacy [OR: 0.85, 95% CI: 0.30 to 2.44, = 0.76]. A vancomycin trough concentration of 10 to 15 μg/mL can improve clinical efficacy in children. Additionally, avoidance of trough concentrations >15 μg/mL can reduce the incidence of adverse reactions.
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http://dx.doi.org/10.1128/aac.00138-22DOI Listing
July 2022

Electrolyte design for inorganic-rich solid-electrolyte interfaces to enable low-temperature Li metal batteries.

Chem Commun (Camb) 2022 Aug 9;58(64):8994-8997. Epub 2022 Aug 9.

State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.

Ether-based electrolyte promotes robust LiF/LiNO-rich solid-electrolyte interphases (SEIs) with favorable interfacial conduction and accommodation, thus decreasing operation temperatures of Li metal batteries to -40 °C. At -30 °C, the Li‖NiCoAlO battery achieves >80% retention (130 mA h g) of its room-temperature capacity, and presents stable cycling over 100 cycles.
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http://dx.doi.org/10.1039/d2cc03096aDOI Listing
August 2022

Porous ZnO Nanosphere Inherently Encapsulated in Carbon Framework as a High-Performance Anode For Ni-Zn Secondary Batteries.

Front Chem 2022 30;10:936679. Epub 2022 Jun 30.

Key Laboratory for Ecological Metallurgy of Multimetallic Mineral (Ministry of Education), School of Metallurgy, Northeastern University, Shenyang, China.

Nickel-zinc (Ni-Zn) secondary battery that is environmentally friendly and inexpensive has been regarded as a promising rechargeable battery system. However, the generation of deformation and dendrites of the traditional zinc anode during the cycling can cause capacity degradation and impede its practical application. Herein, we design a hierarchical ZnO nanosphere coated with an inherently derived ZIF-8 porous carbon shell ([email protected]) using a simple controllable method. The conductive carbon shell and porous ZnO core can provide more active sites, allow the fast transfer of electrons, and buffer the volume expansion of the electrode effectively. Benefiting from the synergistic effect amid the inherently ZIF-8-derived carbon shell and ZnO core, [email protected] nanospheres exhibit a satisfying capacity of 316 mAh g at a current density of 1 A g after 50 cycles and an outstanding rate capacity when acting as the anode for a Ni-Zn secondary battery with merchant agglomerative Ni(OH) as the cathode. These results imply that the [email protected] nanosphere is a hopeful anode for a high-energy Ni-Zn secondary battery.
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http://dx.doi.org/10.3389/fchem.2022.936679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280264PMC
June 2022

Impact of Rituximab and Corticosteroids on Late Cytopenias Post-Chimeric Antigen Receptor T Cell Therapy.

Transplant Cell Ther 2022 Jul 14. Epub 2022 Jul 14.

Division of Hematology-Oncology and Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida.

Chimeric antigen receptor (CAR) T cell therapy represents a significant advancement in the treatment of patients with relapsed/refractory B cell lymphoid malignancies. Cytokine release syndrome and immune effector cell-associated neurotoxicity represent the most acute serious adverse events post CAR T cell therapy but the occurrence and persistence of cytopenias post CAR T cell therapy represent a significant adverse event and a management challenge. While most patients typically recover blood counts by 30 days, a significant subset of patients have persistent or late cytopenias beyond 30 days. Patients receiving CAR T cell are heavily pre-treated and the impact of prior therapies on late cytopenias is not well understood. In this study, we found an association between increased number of rituximab infusions and/or cumulative rituximab dose received prior to CAR T cell infusion and persistent anemia and thrombocytopenia at 90 and 180 days afterwards. An overall increased number of prior lines of therapy was also associated with persistent lymphopenia and anemia at 90 days while receiving a prior autologous hematopoietic cell transplant was associated with a greater risk of neutropenia and lymphopenia.
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http://dx.doi.org/10.1016/j.jtct.2022.07.009DOI Listing
July 2022

Yak Gut Microbiota: A Systematic Review and Meta-Analysis.

Front Vet Sci 2022 28;9:889594. Epub 2022 Jun 28.

Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center, Rotterdam, Netherlands.

The yak () is closely related to common cows (), but is clearly a distinct species. Yaks are of substantial importance to food and leather production in certain high-altitude regions of Asia. The animal is increasing elsewhere as well, mainly because of the perceived health benefits of its milk. Like all ruminants, the animal harbors a complex community of microbial cells in its gut, crucial for its physiology. Despite yaks being important domestic animals, the composition of its gut microbiota and how the composition is guided by its specific high-altitude environment remains largely uncategorized. Hence, online databases (Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar) were searched for articles on yak intestinal microbiota. The pooled taxonomic abundance was compared between regions, sexes, different age groups, and feeding patterns. The gut microbiota distribution across different yak intestinal segments was established through pooled average taxonomic abundance. A total of 34 studies met the inclusion criteria and yielded information on 982 unique yak gut microbiota samples. An analysis of overall pooled microbiota revealed a segmented microbial community composition of the yak gut. Yak rumen microbiota was significantly influenced by difference in region, sex, and feeding patterns, the latter factor being dominant in this respect. Yak microbiome is shaped by the feeding strategy and provides an obvious avenue for improving health and productivity of the animal. More generally, the current segmental description of physiological gut microbiome provides insight into how the microbiology of this animal has adapted itself to help comping yaks with its high-altitude habitat.
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http://dx.doi.org/10.3389/fvets.2022.889594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274166PMC
June 2022

Effects of miR-124-3p Silencing on Neuronal Damage in the Hippocampus of Depression Rats by Regulating STAT3 Gene.

Comput Math Methods Med 2022 30;2022:3733656. Epub 2022 Jun 30.

Second Department of Encephalopathy, Penglai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264000, China.

Objective: A large amount of evidence shows that the abnormal expression of miRNA plays an important role in the development of depression. Therefore, we investigated the effect of miR-124-3p on neuronal damage in the hippocampus of depression rats.

Methods: The target genes of miR-124-3p were predicted by the database; the depression model was prepared by subcutaneous injection of corticosterone (CORT), and LV-miR-124-3p asponge lentiviral suspension was given to determine the weight of rats and open-field test, sugar preference experiment, Serum CORT, 5-HT, DA, and NE were measured, observe and record the behavior of rats, including behavior, diet, and hair. The expression of miR-124-3p, STAT3, Bcl-2, and Bax in rat hippocampus was measured. The rat hippocampal neuron cells were extracted and transfected with miR-124-3p inhibitor; the cells were cultured with CORT, and the cell survival rate was evaluated by MTT experiment, and the expressions of miR-124-3p, STAT3, Bcl-2, and Bax in the cells were detected. Luciferase reporter gene verifies the targeted regulation of miR-124-3p on STAT3.

Results: Compared with depression rats, silencing miR-124-3p increased the weight of the rats, increased the number of open-field activities, and significantly improved the general state and pathological state of the rats. The sugar water preference rate was significantly increased, the CORT content in the serum of rats decreased significantly, and the levels of 5-HT, DA, and NE increased significantly. After the treatment of silencing miR-124-3p, the expression level of miR-124-3p was decreased, while the STAT3 mRNA and protein expression levels were increased. And the protein and mRNA expression levels of Bcl-2 were increased, and the Bax protein and mRNA expression were decreased. Cell experiments verified that silencing miR-124-3p increased cell survival, the expression level of miR-124-3p decreased remarkably, while the expression levels of STAT3 mRNA and protein increased significantly. Silencing miR-124-3p reversed the effects of CORT treatment on miR-124-3p and STAT3 in neuronal cells. The luciferase reporter gene experiment confirmed that miR-124-3p targets and regulates STAT3 expression.

Conclusion: Silencing miR-124-3p may protect hippocampal neurons from damage in depression rats by upregulating STAT3 gene.
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http://dx.doi.org/10.1155/2022/3733656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262509PMC
July 2022

Physiological and transcriptomic responses of to ciprofloxacin reveal molecular mechanisms for antibiotic removal.

iScience 2022 Jul 18;25(7):104638. Epub 2022 Jun 18.

School of Resources & Environmental Science, Hubei International Scientific and Technological Cooperation Base of Sustainable Resource and Energy, Hubei Key Laboratory of Biomass-Resources Chemistry and Environmental Biotechnology, Wuhan University, Wuhan 430079, P.R. China.

Microalgae-based technology is an effective and environmentally friendly method for antibiotics-contaminated wastewater treatment. To assess the tolerance and removal ability of to ciprofloxacin (CIP), this study comprehensively revealed the responses of to CIP exposure and its degradation processes through physiological and transcriptomic analyses. Although the photosynthetic system was inhibited, the growth of was not negatively affected by CIP. Dissolved organic matter was analyzed and indicated that humic-like substances were released to alleviate the stress of CIP. In addition, the maximum removal of CIP was 83.3% under 20 mg L CIP exposure. HPLC-MS/MS and RNA-Seq analyses suggested that CIP could be bioaccumulated and biodegraded by through the reactions of hydroxylation, demethylation, ring cleavage, oxidation, dehydrogenation, and decarboxylation with the help of intracellular oxidoreductases, especially cytochrome P450. Collectively, this research shows that have a great potential for removing CIP from wastewater.
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http://dx.doi.org/10.1016/j.isci.2022.104638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254343PMC
July 2022

Human Leukocyte Antigen Fine-Mapping and Correlation Analysis of Han and Minority Leprosy Patients in Southern China.

Front Genet 2022 13;13:888361. Epub 2022 Jun 13.

Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, China.

Leprosy is very prevalent in many populations around the world, which is well known that both alleles for human leukocyte antigen (HLA) as well as single nucleotide polymorphisms (SNPs) in the HLA region are common in leprosy patients. Previous studies have identified leprosy-associated susceptibility genes that explain only part of disease risk and heritability. In view of the complicated characteristics of the major histocompatibility complex (MHC) region, this study aimed to explore the development and variation of HLA in leprosy and its possible mechanism. Previous genome-wide association data were extracted from Han and minority populations in southern China for HLA fine-mapping studies. Insertion and deletion (INDEL), SNP, and copy number variation (CNV) imputation were determined by using the Thousand People Database (1KGP Phase 3 Dataset) as a reference panel. The HAN-MHC database was used to input the HLA classical alleles and amino acids in the MHC region, and further step-regression analysis was performed to analyze independent variation signals associated with leprosy. The most significant locus rs75324027 (the same locus as rs602875 in the HLA-DR region) [ = 7.49E-09, OR= 0.62, 95%,CI: 0.52-0.73] in the intergene region between HLA-DQA1 and HLA-DRB1 was related with leprosy in M-S(Han leprosy patients in south China)disease. In M-SM (Leprosy patients of ethnic minorities in south China)disease, one of the most significant loci of the HLA-DQB1 gene was 6-32626438-A-T ( = 4.49E-08, OR = 0.36, 95%,CI: 0.25-0.52). Therefore, rs75324027 is a locus in M-S disease, and 6-32626438-a-T may be a new locus in M-SM disease. The interaction between 6 and 32626438-A-T and RS75324027 was analyzed, and A significant interaction relationship was found. In the optimal model, the accuracy of prediction was 0.5974, cross-validation Consistency:10, = 0.0107. In conclusion, this study is the first to assess the association between HLA and leprosy susceptibility in Han and other minority populations in southern China using the Thousand Population database and the Han MHC database. In addition, our analysis validated the previously reported locus rs602875 in the HLA-DR region and for the first time identified an unreported independent locus in leprosy among ethnic minorities in southern China.
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http://dx.doi.org/10.3389/fgene.2022.888361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234480PMC
June 2022

Didecyldimethylammonium bromide: Application to control biofilms of Staphylococcus aureus and Pseudomonas aeruginosa alone and in combination with slightly acidic electrolyzed water.

Food Res Int 2022 Jul 9;157:111236. Epub 2022 Apr 9.

College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

This project explored the antibacterial mechanism of didecyldimethylammonium bromide (DDAB) toward Staphylococcus aureus and Pseudomonas aeruginosa, and its removal effect on biofilms. Furthermore, we explored the effect of treatment by DDAB combined with slightly acidic electrolyzed water (SAEW) on biofilms of S. aureus or P. aeruginosa. First, DDAB has bacteriostatic and biofilm removal effects. Second, The effect of DDAB combined with SAEW on biofilm is more obvious than that of the two alone. DDAB at a concentration of 16 MIC combined with SAEW (ACC 30 mg/L, ORP 875 mV, pH 6.30) completely cleared the biofilm. In addition, the results of Confocal laser scanning microscopy (CLSM), Field emission scanning electron microscopy (FESEM) and Attenuated total reflection-Fourier-transform infrared spectroscopy (ATR-FTIR) showed that DDAB combined with SAEW could disrupt the structure of biofilms, reduce polysaccharides, proteins and phospholipids in biofilms. This method has the potential to be used in food production chains to control S. aureus and P. aeruginosa and their biofilms, and it can be used in other industries.
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http://dx.doi.org/10.1016/j.foodres.2022.111236DOI Listing
July 2022

Machine learning to predict post-operative acute kidney injury stage 3 after heart transplantation.

BMC Cardiovasc Disord 2022 06 25;22(1):288. Epub 2022 Jun 25.

Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.

Background: Acute kidney injury (AKI) stage 3, one of the most severe complications in patients with heart transplantation (HT), is associated with substantial morbidity and mortality. We aimed to develop a machine learning (ML) model to predict post-transplant AKI stage 3 based on preoperative and perioperative features.

Methods: Data from 107 consecutive HT recipients in the provincial center between 2018 and 2020 were included for analysis. Logistic regression with L2 regularization was used for the ML model building. The predictive performance of the ML model was assessed using the area under the curve (AUC) in tenfold stratified cross-validation and was compared with that of the Cleveland-clinical model.

Results: Post-transplant AKI occurred in 76 (71.0%) patients including 15 (14.0%) stage 1, 18 (16.8%) stage 2, and 43 (40.2%) stage 3 cases. The top six features selected for the ML model to predicate AKI stage 3 were serum cystatin C, estimated glomerular filtration rate (eGFR), right atrial long-axis dimension, left atrial anteroposterior dimension, serum creatinine (SCr) and FVII. The predictive performance of the ML model (AUC: 0.821; 95% confidence interval [CI]: 0.740-0.901) was significantly higher compared with that of the Cleveland-clinical model (AUC: 0.654; 95% [CI]: 0.545-0.763, p < 0.05).

Conclusions: The ML model, which achieved an effective predictive performance for post-transplant AKI stage 3, may be helpful for timely intervention to improve the patient's prognosis.
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http://dx.doi.org/10.1186/s12872-022-02721-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233761PMC
June 2022

Predictors of poor serologic response to COVID-19 vaccine in patients with cancer: a systematic review and meta-analysis.

Eur J Cancer 2022 Jun 2;172:41-50. Epub 2022 Jun 2.

Department of Forensic Pathology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China. Electronic address:

Backgrounds: Patients with cancer presented a lower probability to obtain seroconversion after a complete course of COVID-19 vaccination. However, little was known on the factors that predict poor seroconversion in this frail population.

Methods: We searched the PubMed, EMBASE, and China National Knowledge Infrastructure databases for all articles within a range of published years from 2019 to 2022 on the predictors of response to COVID-19 vaccine in patients with cancer (last search was updated on 2st March 2022). The odds ratio corresponding to the 95% confidence interval was used to assess the outcome. The statistical heterogeneity among studies was assessed with the Q-test and I statistics. The review was registered with PROSPERO (CRD42022315687) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Twenty cohort studies met the inclusion criteria for this study, with 5,499 patients with cancer. We found that advanced age, male patients, and metastatic disease increased negative seropositivity to COVID-19 vaccine. Immunoglobulin heavy chain variable mutation status, high concentration of Ig G, Ig M, and Ig A were correlated with seropositivity. Relating to cancer treatment strategy, anti-CD20 therapy within recent 12 months and chemotherapy were negatively correlated with seroconversion. Meta-analysis found no significant difference associated with targeted treatment, immunotherapy, and endocrine treatment.

Conclusions: Our meta-analysis assessed the factors that predict poor seroconversion in order to plan better prevention strategies in this frail population. The results proposed that enhanced vaccination strategies would be beneficial for the special patients such as advanced male, or patients receiving active chemotherapy, and carefully prevention should be emphasised even after a complete course of vaccination.
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http://dx.doi.org/10.1016/j.ejca.2022.05.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160160PMC
June 2022

Imputation of the major histocompatibility complex region identifies major independent variants associated with bullous pemphigoid and dermatomyositis in Han Chinese.

J Dermatol 2022 Jun 25. Epub 2022 Jun 25.

Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

As autoimmune skin diseases, both bullous pemphigoid (BP) and dermatomyositis (DM) show significant associations with the major histocompatibility complex (MHC) region. In fact, the coexistence of BP and DM has been previously reported. Therefore, we hypothesized that there may be a potential genetic correlation between BP and DM. Based on data for 312 BP patients, 128 DM patients, and 6793 healthy control subjects, in the MHC region, we imputed single-nucleotide polymorphisms (SNP), insertions and deletions (INDEL), and copy number variations (CNV) using the 1KGP phase 3 dataset and amino acids (AA) and SNP using a Han-MHC reference database. An association study revealed the most significant SNP associated with BP, namely, rs580921 (p = 1.06E-08, odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.37-1.90), which is located in the C6orf10 gene, and the most significant classic human leukocyte antigen (HLA) allele associated with DM, namely, HLA-DPB1*1701 (p = 6.56E-10, OR = 3.61, 95% CI = 2.40-5.42). Further stepwise regression analyses with rs580921 identified a threonine at position 163 of the HLA-B gene as a new independent disease-associated AA, and HLA-DPB1*1701 indicated that no loci were significant. Three-dimensional ribbon models revealed that the HLA-B AA position 163 (p = 3.93E-07, OR = 1.64, 95% CI = 1.35-1.98) located in the α2 domain of the HLA-B molecule was involved in the process of specific antigen presentation. The calculations showed that there was no significant genetic correlation between BP and DM. Our study identified three significant loci in the MHC region, proving that the HLA region was significantly correlated with BP and DM separately. Our research highlights the key role of the MHC region in disease susceptibility.
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http://dx.doi.org/10.1111/1346-8138.16499DOI Listing
June 2022

Plant Diversity and Fungal Richness Regulate the Changes in Soil Multifunctionality in a Semi-Arid Grassland.

Biology (Basel) 2022 Jun 6;11(6). Epub 2022 Jun 6.

Key Laboratory of Vegetation Ecology, Institute of Grassland Science, Northeast Normal University, Ministry of Education, Changchun 130024, China.

Loss in plant diversity is expected to impact biodiversity and ecosystem functioning (BEF) in terrestrial ecosystems. Soil microbes play essential roles in regulating ecosystem functions. However, the important roles and differences in bacterial and fungal diversity and rare microbial taxa in driving soil multifunctionality based on plant diversity remain poorly understood in grassland ecosystems. Here, we carried out an experiment in six study sites with varied plant diversity levels to evaluate the relationships between soil bacterial and fungal diversity, rare taxa, and soil multifunctionality in a semi-arid grassland. We used Illumina HiSeq sequencing to determine soil bacterial and fungal diversity and evaluated soil functions associated with the nutrient cycle. We found that high diversity plant assemblages had a higher ratio of below-ground biomass to above-ground biomass, soil multifunctionality, and lower microbial carbon limitation than those with low diversity. Moreover, the fungal richness was negatively and significantly associated with microbial carbon limitations. The fungal richness was positively related to soil multifunctionality, but the bacterial richness was not. We also found that the relative abundance of saprotrophs was positively correlated with soil multifunctionality, and the relative abundance of pathogens was negatively correlated with soil multifunctionality. In addition, the rare fungal taxa played a disproportionate role in regulating soil multifunctionality. Structural equation modeling showed that the shift of plant biomass allocation patterns increased plant below-ground biomass in the highly diverse plant plots, which can alleviate soil microbial carbon limitations and enhance the fungal richness, thus promoting soil multifunctionality. Overall, these findings expand our comprehensive understanding of the critical role of soil fungal diversity and rare taxa in regulating soil multifunctionality under global plant diversity loss scenarios.
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http://dx.doi.org/10.3390/biology11060870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220314PMC
June 2022

Tropomyosin Is Potential Markers for the Diagnosis and Prognosis of Bladder Cancer.

Dis Markers 2022 13;2022:6936262. Epub 2022 Jun 13.

Department of Urology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.

Objective: To investigate the correlation between tropomyosin (TM) and clinical characteristics of bladder cancer. In addition, the relationship between TM and immune cell infiltration in bladder cancer was further analyzed.

Methods: Based on The Cancer Genome Atlas (TCGA) database, the relationship between TM expression and clinicopathological features in bladder cancer was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the value of TM as a diagnostic marker for bladder cancer. Univariate and multivariate Cox regression was used to analyze the independent factors affecting the prognosis of patients with bladder cancer. The relationship between TM and immune cell infiltration was analyzed.

Results: ROC curve showed that TPM1, TPM2, and TPM3 had significant diagnostic ability (AUC was 0.845, 0.848, and 0.873, respectively). The high expression of TPM1 and TPM2 is associated with poor overall and disease-specific survival in patients with bladder cancer ( < 0.05). Multivariate Cox analysis showed that age and TPM1 were independent prognostic factors. The expression levels of TPM1, TPM2, TPM3, and TPM4 in low grade bladder cancer were lower than those in high grade bladder cancer ( < 0.05). TPM1 and TPM2 are positively correlated with the infiltration of macrophages and NK cells in bladder cancer. TPM3 is positively associated with Th2. TPM4 is positively correlated with Th1 cells, macrophages, and neutrophils ( < 0.05).

Conclusions: TPM1 and TPM2 are effective markers for the diagnosis of bladder cancer. TPM1 is an independent prognostic factor for bladder cancer. TM is also associated with the infiltration of various immune cells in bladder cancer. TM may have influenced the development of bladder cancer through immune inhibition.
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http://dx.doi.org/10.1155/2022/6936262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208974PMC
June 2022

Targeted B-domain deletion restores F8 function in human endothelial cells and mice.

Signal Transduct Target Ther 2022 06 20;7(1):189. Epub 2022 Jun 20.

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, 410078, China.

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http://dx.doi.org/10.1038/s41392-022-01016-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207027PMC
June 2022

Comprehensive Analysis of Congenital Adrenal Hyperplasia Using Long-Read Sequencing.

Clin Chem 2022 07;68(7):927-939

Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 110 Xiangya Road, Changsha 410078, Hunan, China.

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that has been included in newborn screening programs. Current approaches to gene testing for CAH are facing challenges because of the complexity of the CYP21A2 locus and genetic heterogeneity of the disease.

Methods: A comprehensive analysis of CAH (CACAH) combining long-range locus-specific PCR and long-read sequencing (LRS) was developed to perform full sequence analysis of 5 common CAH candidate genes, including CYP21A2, CYP11B1, CYP17A1, HSD3B2, and StAR. In a blind retrospective study, the clinical utility of CACAH was evaluated in 37 samples by comparing to standard CAH testing using multiplex ligation-dependent probe amplification (MLPA) plus Sanger sequencing.

Results: Of the 37 clinical samples, a total of 69 pathogenic variants were identified, comprising 65 CYP21A2 variants, 2 HSD3B2 variants, and 2 CYP17A1 variants. For CYP21A2, the most frequent variant was c.518T > A (29.2%), followed by c.293-13C/A > G (21.5%). Compared with the current CAH testing using MLPA plus Sanger sequencing, the CACAH assay showed 100% specificity and 100% sensitivity, and precisely determined the junction sites of deletions/insertions and cis-trans configuration of multiple variants without analyzing family samples. Moreover, CACAH identified a case carrying 2 copies of CYP21A1 with the c.1451_1452delinsC variant on the same chromosome, which was not confirmed by MLPA plus Sanger sequencing.

Conclusion: LRS-based CACAH can determine all genotypes of CAH accurately and reliably in one assay, presenting a comprehensive approach for CAH genetic diagnosis and carrier screening.
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http://dx.doi.org/10.1093/clinchem/hvac046DOI Listing
July 2022

Clinical characteristics, prognostic indicators, and survival outcomes in intravascular lymphoma: Mayo Clinic experience (2003-2018).

Am J Hematol 2022 Jun 17. Epub 2022 Jun 17.

Department of Haematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida, USA.

Intravascular lymphoma (IVL) is a rare extranodal non-Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003-2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS-IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non-CNS-IVL patients with abnormal FDG-PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS-IVL and 63.5% (35/55) had non-CNS-IVL. CNS-IVL group consists of clinically isolated CNS involvement (CNS-only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M-IVL) (14.5%; 8/55). Non-CNS-IVL group consists of clinically isolated skin involvement (skin-only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P-IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B-cell IVL. Rituximab + high-dose methotrexate-based regimen were used in 75% (12/16) of CNS-IVL patients and RCHOP in 60% (17/28) of non-CNS-IVL patients. Estimated 5-year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin-only IVL was associated with excellent survival. Platelet count <150x10 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.
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http://dx.doi.org/10.1002/ajh.26635DOI Listing
June 2022

Efficacy of Parainfluenza Virus 5 (PIV5)-vectored Intranasal COVID-19 Vaccine as a Single Dose Vaccine and as a Booster against SARS-CoV-2 Variants.

bioRxiv 2022 Jun 8. Epub 2022 Jun 8.

Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has greatly reduced coronavirus disease 2019 (COVID-19)-related deaths and hospitalizations, but waning immunity and the emergence of variants capable of immune escape indicate the need for novel SARS-CoV-2 vaccines. An intranasal parainfluenza virus 5 (PIV5)-vectored COVID-19 vaccine CVXGA1 has been proven efficacious in animal models and blocks contact transmission of SARS-CoV-2 in ferrets. CVXGA1 vaccine is currently in human clinical trials in the United States. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccines expressing additional antigen SARS-CoV-2 nucleoprotein (N) or SARS-CoV-2 variant spike (S) proteins of beta, delta, gamma, and omicron variants against homologous and heterologous challenges in hamsters. A single intranasal dose of CVXGA1 induces neutralizing antibodies against SARS-CoV-2 WA1 (ancestral), delta variant, and omicron variant and protects against both homologous and heterologous virus challenges. Compared to mRNA COVID-19 vaccine, neutralizing antibody titers induced by CVXGA1 were well-maintained over time. When administered as a boost following two doses of a mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive neutralizing antibodies compared to three doses of a mRNA vaccine. In addition to the S protein, the N protein provides added protection as assessed by the highest body weight gain post-challenge infection. Our data indicates that PIV5-vectored COVID-19 vaccines, such as CVXGA1, can serve as booster vaccines against emerging variants.

Importance: With emerging new variants of concern (VOC), SARS-CoV 2 continues to be a major threat to human health. Approved COVID-19 vaccines have been less effective against these emerging VOCs. This work demonstrates the protective efficacy, and strong boosting effect, of a new intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters.
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http://dx.doi.org/10.1101/2022.06.07.495215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196109PMC
June 2022

LncRNA SNHG6 inhibits autophagy of gastric carcinoma cells via PI3K/AKT/mTOR signaling pathway.

Am J Transl Res 2022 15;14(5):2861-2873. Epub 2022 May 15.

Graduate Department of Shanxi Medical University Taiyuan 030001, Shanxi, China.

Objective: To investigate the role of lncRNA SNHG6 (SNHG6) in gastric carcinoma (GC) and its relationship with the PI3K/AKT/mTOR signaling pathway in order to provide more comprehensive and reliable reference for the diagnosis and treatment of GC.

Methods: GC patients admitted to our hospital from May 2017 to August 2018 as well as healthy individuals who underwent physical examinations during the same time period were enrolled in this study. The serum SNHG6 level was quantified. Patients were followed up for 3 years to analyze the significance of SNHG6 in the diagnosis and treatment of GC. Finally, assays were performed to determine the influences of SNHG6 and PI3K/AKT/mTOR signaling pathway on biological behaviors and autophagy ability of GC cells.

Results: SNHG6 showed high expression in patients with GC and its expression decreased after therapy. SNHG6 also demonstrated a favorable predictive value for the development of GC and the death of patients. The survival curve suggested that increased SNHG6 indicated a higher risk of death. Additionally, mRNA of PI3K/AKT/mTOR pathway related molecules was highly expressed in GC patients. In assays, GC cells showed stronger viability and invasion activity and weaker apoptosis and autophagy ability after targeted up-regulation of SNHG6. According to the rescue assay, the effect of up-regulating SNHG6 on GC cells could be completely reversed by suppressing the PI3K/AKT/mTOR pathway.

Conclusion: With high expression in patients with GC, SNHG6 can promote the development of GC by activating the PI3K/AKT/mTOR signaling pathway and suppressing the autophagy of cells. Therefore, it is a potential breakthrough in the diagnosis and treatment of GC in the future.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185092PMC
May 2022
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