Publications by authors named "Bin Zhang"

5,015 Publications

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Clinical efficacy of large channel percutaneous lumbar endoscopic decompression in the treatment of lumbar spinal stenosis secondary to old compression fractures.

World Neurosurg 2022 Jun 29. Epub 2022 Jun 29.

Department of Orthopedics Surgery, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Reigion, Chengu, Sichuan.

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http://dx.doi.org/10.1016/j.wneu.2022.06.111DOI Listing
June 2022

Prognostic significance of 4R lymph node dissection in patients with right primary non-small cell lung cancer.

World J Surg Oncol 2022 Jul 1;20(1):222. Epub 2022 Jul 1.

Department of Lung Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, Binshui Road, Tianjin, China.

Background: To investigate the prognostic significance of station 4R lymph node (LN) dissection in patients who underwent operations for right primary non-small cell lung cancer (NSCLC).

Methods: We performed a retrospective study involving patients with right primary NSCLC who received lobotomy or pneumonectomy with mediastinal LN dissection between January 2011 and December 2017. Propensity score matching was performed. Disease-free survival (DFS) and overall survival (OS) were compared between patients with and without station 4R dissection.

Results: Our study included 2070 patients, with 207 patients having no station 4R dissection (S4RD- group) and 1863 patients having station 4R dissection (S4RD+ group). The 4R LN metastasis rate was 13.4% (142/1748), higher than that for other mediastinal LN metastases. Compared with the S4RD- group, the S4RD+ group had higher 5-year DFS (48.1% vs. 39.1%, P = 0.009) and OS (54.4% vs. 42.8%, P = 0.025). Station 4R dissection was an independent risk factor for DFS (odds ratio, OR, 1.28, 95% confidence interval, CI, 1.08-1.64, P = 0.007) and OS (OR 1.31, 95% CI 1.04-1.63, P = 0.018). Patients with adjuvant chemotherapy had a better prognosis after station 4R dissection than those without adjuvant chemotherapy (57.4% vs. 52.3%, P = 0.006). The 5-year OS in the station 4R metastasis group was lower than that in the station 4R non-metastasis group (26.9% vs. 44.3%, P = 0.006) among N2 patients. The 5-year OS of the single-station 4R metastasis group was lower than that of the single-station 7 metastasis group (15.7% vs. 51.6%, P = 0.002).

Conclusions: Station 4R metastasis was the highest among all the mediastinal station metastases in right primary NSCLC patients. Station 4R dissection can improve the prognosis and should be recommended as a routine procedure for these patients.
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http://dx.doi.org/10.1186/s12957-022-02689-wDOI Listing
July 2022

Two Magnesium Transporters in the Chloroplast Inner Envelope Essential for Thylakoid Biogenesis in Arabidopsis.

New Phytol 2022 Jul 1. Epub 2022 Jul 1.

Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA.

● Magnesium (Mg ) serves as a cofactor for a number of photosynthetic enzymes and the central metal of chlorophyll in the chloroplast. However, little is known on the molecular mechanism of Mg transport across chloroplast envelope. ● Here, we report functional characterization of two transport proteins in Arabidopsis, Magnesium Release 8 (MGR8) and MGR9, of the ACDP/CNNM family evolutionarily conserved in all lineages of life. ● Both MGR8 and MGR9 genes were expressed ubiquitously, and their encoded proteins were localized in the inner envelope of chloroplasts. Mutations of both MGR8 and MGR9, but not any of them alone, resulted in albino ovules and chlorotic seedlings. Further analysis revealed severe defects in thylakoid biogenesis and assembly of photosynthetic complexes in the double mutant. Both MGR8 and MGR9 functionally complemented the growth of the Salmonella typhimurium mutant strain MM281 which lacks Mg uptake capacity. The embryonic and early seedling defects of mgr8/mgr9 double mutant were amended by the expression of MGR9 under the embryo-specific ABI3 promoter. The partially rescued mutant plants were hypersensitive to Mg deficient condition and contains less Mg in the chloroplast than the wild type. ● Taken together, we conclude that MGR8 and MGR9 serve as Mg transporters responsible for chloroplast Mg uptake.
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http://dx.doi.org/10.1111/nph.18349DOI Listing
July 2022

Plasma CXCL14 as a Candidate Biomarker for the Diagnosis of Lung Cancer.

Front Oncol 2022 8;12:833866. Epub 2022 Jun 8.

Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Background: Effective biomarkers for early diagnosis of lung cancer are needed. Previous studies have indicated positive associations between abnormal circulating cytokines and the etiology of lung cancer.

Methods: Blood samples were obtained from 286 patients with pretreatment lung cancer and 80 healthy volunteers. Circulating cytokine levels were detected with a Luminex assay and enzyme-linked immunosorbent assay (ELISA). Urine samples were obtained from 284 patients and 122 healthy volunteers. CXC chemokine ligand 14 (CXCL14) expression in tumors and nontumor regions of lung tissues from 133 lung cancer cases was detected by immunohistochemical (IHC) staining and immunofluorescence (IF) staining of formalin fixed paraffin-embedded (FFPE) tissues.

Results: Compared with healthy volunteers, a 65.7-fold increase was observed in the level of CXCL14 in the plasma of lung cancer patients, and a 1.7-fold increase was observed in the level of CXCL14 in the urine of lung cancer patients, achieving a 0.9464 AUC (area under the curve) value and a 0.6476 AUC value for differentiating between lung cancer patients and healthy volunteers, respectively. Stromal CXCL14 expression was significantly associated with advanced pathologic stage (<0.001), pathologic N stage (<0.001), and recurrence and metastasis (=0.014). Moreover, multivariate analysis suggested stromal CXCL14 expression as an independent predictor of DFS and OS.

Conclusions: Our study demonstrates that CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer.

Impact: CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer.
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http://dx.doi.org/10.3389/fonc.2022.833866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235466PMC
June 2022

A nomogram to predict the survival of gastric cancer patients who underwent radical gastrectomy in the west of China.

Asian J Surg 2022 Jun 26. Epub 2022 Jun 26.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.06.106DOI Listing
June 2022

Enhanced thermal transportation across an electrostatic self-assembly of black phosphorene and boron nitride nanosheets in flexible composite films.

Nanoscale 2022 Jun 29. Epub 2022 Jun 29.

Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China.

For effective heat dissipation in portable electronics, there is a great demand for lightweight and flexible films with superior thermal transport properties. Despite extensive efforts, enhancing the intrinsic low thermal conductivity of polymers while simultaneously maintaining their flexibility is difficult to achieve due to the dilemma of quarrying appropriate filler loading. Herein, a cellulose nanofiber-based film with high in-plane thermal conductivity up to 72.53 W m K was obtained by harnessing the advantage of functionalized boron nitride nanosheets (-BNNS) and black phosphorene (BP) the vacuum filtration process. Besides, our unique design based on the electrostatic coupling of black phosphorene and functionalized boron nitride nanosheets significantly reduced the interfacial thermal resistance of the composite films. This work offers new insights into establishing a facile, yet efficient approach to preparing high thermal conductive heat spreaders.
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http://dx.doi.org/10.1039/d2nr02421gDOI Listing
June 2022

Epidemiologic Correlation and Drug Resistance Analysis of Pathogenic Bacteria in Different Open Limb Injury External Conditions.

Orthop Surg 2022 Jun 28. Epub 2022 Jun 28.

Department of Orthopedic Surgery and Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens.

Methods: This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In-hospital infection of clean limb incision, II, In-hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non-motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram-positive bacteria (G+, mainly including Staphylococcus) and Gram-negative bacteria (G-, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two-way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P < 0.05.

Results: There was no significant difference in the distribution of pathogens between Groups II and Groups III (P>0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G- were resistant to the first- and the second-generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third-generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta-lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria.

Conclusion: In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out-of-hospital infection was lower than that of hospital infection.
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http://dx.doi.org/10.1111/os.13203DOI Listing
June 2022

Bioactive polysaccharides and oligosaccharides from garlic (Allium sativum L.): Production, physicochemical and biological properties, and structure-function relationships.

Compr Rev Food Sci Food Saf 2022 Jun 28. Epub 2022 Jun 28.

Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Tai'an, China.

Garlic is a common food, and many of its biological functions are attributed to its components including functional carbohydrates. Garlic polysaccharides and oligosaccharides as main components are understudied but have future value due to the growing demand for bioactive polysaccharides/oligosaccharides from natural sources. Garlic polysaccharides have molecular weights of 1 × 10 to 2 × 10  Da, containing small amounts of pectins and fructooligosaccharides and large amounts of inulin-type fructans ((2→1)-linked β-d-Fruf backbones alone or with attached (2→6)-linked β-d-Fruf branched chains). This article provides a detailed review of research progress and identifies knowledge gaps in extraction, production, composition, molecular characteristics, structural features, physicochemical properties, bioactivities, and structure-function relationships of garlic polysaccharides/oligosaccharides. Whether the extraction processes, synthesis approaches, and modification methods established for other non-garlic polysaccharides are also effective for garlic polysaccharides/oligosaccharides (to preserve their desired molecular structures and bioactivities) requires verification. The metabolic processes of ingested garlic polysaccharides/oligosaccharides (as food ingredients/dietary supplements), their modes of action in healthy humans or populations with chronic conditions, and molecular/chain organization-bioactivity relationships remain unclear. Future research directions related to garlic polysaccharides/oligosaccharides are discussed.
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http://dx.doi.org/10.1111/1541-4337.12972DOI Listing
June 2022

Infralow-frequency transcranial magnetic stimulation as a therapy for generalized anxiety disorder: A randomized clinical trial.

Compr Psychiatry 2022 Jun 11;117:152332. Epub 2022 Jun 11.

Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China. Electronic address:

Background: Generalized anxiety disorder (GAD) is a common chronic mental disorder, and it also can cause depressive symptoms and cognitive impairment. The primary aim of this study was to determine whether inflow-frequency transcranial magnetic stimulation (ILF-TMS) improves anxiety symptoms in patients with GAD.

Methods: Sixty-two patients with GAD were randomly divided into 2 groups. Thirty-one patients in the active ILF-TMS group and 31 patients in the sham ILF-TMS group. All participants were assessed at baseline, week 2, week 4 and week 12. The intention-to-treat methodology was used for the analysis.

Results: The response rate was higher in the active group than in the sham group, with a significant difference at week 12 (response rate: 80.6% vs. 54.8%, respectively; P = 0.03). Although the remission rate was higher in the active group at week 12, there was no statistically significant difference between the groups (remission rate: 71.0% vs. 48.4%; P > 0.05). No statistically significant differences on the Hamilton Depression Rating Scale, Clinical Global Impression scale, and neurocognitive test between groups were observed (overall P > 0.05). Adverse events that occurred in the active group were similar to those in the sham group, with no significant differences (P > 0.05).

Conclusion: The response rate was higher in the active group at the end of the trial, which indicated that ILF-TMS may be an effective and safe adjunctive tool to improve anxiety symptoms in patients with GAD.
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http://dx.doi.org/10.1016/j.comppsych.2022.152332DOI Listing
June 2022

Phenotypic, genomic, and transcriptomic changes in an Acinetobacter baumannii strain after spaceflight in China's Tiangong-2 space laboratory.

Braz J Microbiol 2022 Jun 28. Epub 2022 Jun 28.

Department of Respiratory and Critical Care Medicine, The Second Medical Center & National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, Beijing, China.

Acinetobacter baumannii is an opportunistic pathogen often found in patients with low immunity. It causes nosocomial infections, which are difficult to treat. This bacterium can rapidly mutate, developing resistance to antimicrobials and adapting to environmental stress, thereby increasing its survival. Understanding such adaptive mechanisms will be beneficial for controlling the spread of A. baumannii. Astrobiology studies have demonstrated that microbiomes from astronauts and manned spaceflight environments show resistance to stress and antibiotics. Astronauts also encounter low immunity during spaceflight missions. The extreme conditions of spaceflight provide a unique research platform for studying how opportunistic pathogens such as A. baumannii adapt to conditions such as microgravity and mutate during spaceflight. In this study, we compared phenotypic variations and analyzed genomic and transcriptomic variations in A. baumannii strains exposed to three different conditions: ST1 (64 days on Tiangong-2 space laboratory), GT1 (ground control), and Aba (original strain). Biofilm formation ability of the ST1 strain increased after 64 days of spaceflight. In addition, high-throughput sequencing revealed that some differentially expressed genes were upregulated in the ST1 strain compared to the GT1 strain. These results provide insights into the environmental adaptation of this widespread pathogen.
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http://dx.doi.org/10.1007/s42770-022-00772-8DOI Listing
June 2022

Modality-Specific Segmentation Network for Lung Tumor Segmentation in PET-CT Images.

IEEE J Biomed Health Inform 2022 Jun 27;PP. Epub 2022 Jun 27.

Lung tumor segmentation in PET-CT images plays an important role to assist physicians in clinical application to accurately diagnose and treat lung cancer. However, it is still a challenging task in medical image processing field. Due to respiration and movement, the lung tumor varies largely in PET images and CT images. Even the two images are almost simultaneously collected and registered, the shape and size of lung tumors in PET-CT images are different from each other. To address these issues, a modality-specific segmentation network (MoSNet) is proposed for lung tumor segmentation in PET-CT images. MoSNet can simultaneously segment the modality-specific lung tumor in PET images and CT images. MoSNet learns a modality-specific representation to describe the inconsistency between PET images and CT images and a modality-fused representation to encode the common feature of lung tumor in PET images and CT images. An adversarial method is proposed to minimize an approximate modality discrepancy through an adversarial objective with respect to a modality discriminator and reserve modality-common representation. This improves the representation power of the network for modality-specific lung tumor segmentation in PET images and CT images. The novelty of MoSNet is its ability to produce a modality-specific map that explicitly quantifies the modality-specific weights for the features in each modality. To demonstrate the superiority of our method, MoSNet is validated in 126 PET-CT images with NSCLC. Experimental results show that MoSNet reaches 75.52 ±18.65% (Dice) in CT images and 75.52 ±18.65% (Dice) in PET images, respectively, and also outperforms state-of-the-art lung tumor segmentation methods.
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http://dx.doi.org/10.1109/JBHI.2022.3186275DOI Listing
June 2022

Vestigial-Like 3 Plays an Important Role in Osteoblast Differentiation by Regulating the Expression of Osteogenic Transcription Factors and BMP Signaling.

Calcif Tissue Int 2022 Jun 24. Epub 2022 Jun 24.

Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, 246 Xuefu Road, Nangang, Harbin, 150001, Heilongjiang, People's Republic of China.

Our previous gene profiling analysis showed that the transcription cofactor vestigial-like 3 (VGLL3) gene expression was upregulated by mechanical tension in the mouse cranial suture, coinciding with accelerated osteoblast differentiation. Therefore, we hypothesized that VGLL3 plays a significant role in osteogenic differentiation. To clarify the function of VGLL3 in osteoblasts, we examined its expression characteristics in mouse bone tissue and the osteoblastic cell line MC3T3-E1. We further examined the effects of Vgll3 knockdown on osteoblast differentiation and bone morphogenetic protein (BMP) signaling. In the mouse cranial suture, where membranous ossification occurs, VGLL3 was immunohistochemically detected mostly in the nucleus of osteoblasts, preosteoblasts, and fibroblastic cells. VGLL3 expression in MC3T3-E1 cells was transient and peaked at a relatively early stage of differentiation. RNA sequencing revealed that downregulated genes in Vgll3-knockdown cells were enriched in gene ontology terms associated with osteoblast differentiation. Interestingly, most of the upregulated genes were related to cell division. Targeted Vgll3 knockdown markedly suppressed the expression of major osteogenic transcription factors (Runx2, Sp7/osterix, and Dlx5) and osteoblast differentiation. It also attenuated BMP signaling; moreover, exogenous BMP2 partially restore osteogenic transcription factors' expression in Vgll3-knockdown cells. Furthermore, overexpression of Vgll3 increased the expression of osteogenic transcription factors. These results suggest that VGLL3 plays a critical role in promoting osteoblast differentiation and that part of the process is mediated by BMP signaling. Further elucidation of VGLL3 function will increase our understanding of osteogenesis and skeletal disease etiology.
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http://dx.doi.org/10.1007/s00223-022-00997-7DOI Listing
June 2022

Cholesterol and matrisome pathways dysregulated in astrocytes and microglia.

Cell 2022 Jun;185(13):2213-2233.e25

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

The impact of apolipoprotein E ε4 (APOE4), the strongest genetic risk factor for Alzheimer's disease (AD), on human brain cellular function remains unclear. Here, we investigated the effects of APOE4 on brain cell types derived from population and isogenic human induced pluripotent stem cells, post-mortem brain, and APOE targeted replacement mice. Population and isogenic models demonstrate that APOE4 local haplotype, rather than a single risk allele, contributes to risk. Global transcriptomic analyses reveal human-specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia. APOE4 enhances de novo cholesterol synthesis despite elevated intracellular cholesterol due to lysosomal cholesterol sequestration in astrocytes. Further, matrisome dysregulation is associated with upregulated chemotaxis, glial activation, and lipid biosynthesis in astrocytes co-cultured with neurons, which recapitulates altered astrocyte matrisome signaling in human brain. Thus, APOE4 initiates glia-specific cell and non-cell autonomous dysregulation that may contribute to increased AD risk.
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http://dx.doi.org/10.1016/j.cell.2022.05.017DOI Listing
June 2022

Transcriptome Analysis Reveals Key Genes and Pathways Associated with the Petal Color Formation in Cabbage ( L. var. ).

Int J Mol Sci 2022 Jun 15;23(12). Epub 2022 Jun 15.

Key Laboratory of Biology and Genetic Improvement of Horticultural Crops, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Ministry of Agriculture, #12 Zhong Guan Cun Nandajie Street, Beijing 100081, China.

Petal color is an important agronomic trait in cabbage ( L. var. ). Although the key gene has been functionally characterized, the underlying molecular regulatory mechanism of petal color formation in cabbage is still unclear. In this study, we applied the transcriptome analysis of yellow petals from the cabbage inbred line YL-1 and white petals from the Chinese kale inbred line A192-1 and the -overexpressing transgenic line YF-2 (YL-1 background), which revealed 1928 DEGs common to both the A192-1 vs. YL-1 and the YL-1 vs. YF-2 comparison groups. One key enzyme-encoding gene, , and two key TF-encoding genes, (WRKY) and (SBP), related to carotenoid biosynthesis were significantly up-regulated in both the A192-1 and YF-2 petals, which was consistent with the expression pattern of . We speculate that these key genes may interact with to jointly regulate carotenoid biosynthesis in cabbage petals. This study provides new insights into the molecular regulatory mechanism underlying petal color formation in cabbage.
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http://dx.doi.org/10.3390/ijms23126656DOI Listing
June 2022

Arsenic Trioxide and Venetoclax Synergize against AML Progenitors by ROS Induction and Inhibition of Nrf2 Activation.

Int J Mol Sci 2022 Jun 12;23(12). Epub 2022 Jun 12.

Gehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.

Venetoclax (VEN) in combination with hypomethylating agents induces disease remission in patients with de novo AML, however, most patients eventually relapse. AML relapse is attributed to the persistence of drug-resistant leukemia stem cells (LSCs). LSCs need to maintain low intracellular levels of reactive oxygen species (ROS). Arsenic trioxide (ATO) induces apoptosis via upregulation of ROS-induced stress to DNA-repair mechanisms. Elevated ROS levels can trigger the Nrf2 antioxidant pathway to counteract the effects of high ROS levels. We hypothesized that ATO and VEN synergize in targeting LSCs through ROS induction by ATO and the known inhibitory effect of VEN on the Nrf2 antioxidant pathway. Using cell fractionation, immunoprecipitation, RNA-knockdown, and fluorescence assays we found that ATO activated nuclear translocation of Nrf2 and increased transcription of antioxidant enzymes, thereby attenuating the induction of ROS by ATO. VEN disrupted ATO-induced Nrf2 translocation and augmented ATO-induced ROS, thus enhancing apoptosis in LSCs. Using metabolic assays and electron microscopy, we found that the ATO+VEN combination decreased mitochondrial membrane potential, mitochondria size, fatty acid oxidation and oxidative phosphorylation, all of which enhanced apoptosis of LSCs derived from both VEN-sensitive and VEN-resistant AML primary cells. Our results indicate that ATO and VEN cooperate in inducing apoptosis of LSCs through potentiation of ROS induction, suggesting ATO+VEN is a promising regimen for treatment of VEN-sensitive and -resistant AML.
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http://dx.doi.org/10.3390/ijms23126568DOI Listing
June 2022

Microstructure, Digestibility and Physicochemical Properties of Rice Grains after Radio Frequency Treatment.

Foods 2022 Jun 13;11(12). Epub 2022 Jun 13.

School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Radio frequency (RF) energy has been successfully applied to rice drying, sterilization, and controlling pests. However, the effects of RF treatment on the microstructure, physicochemical properties, and digestibility of rice have rarely been studied. This study investigated the alteration of a multiscale structure, pasting, rheology, and digestibility of rice grains after the RF treatment. A microstructure analysis demonstrated that the RF treatment caused starch gelatinization and protein denaturation in rice grains with an increasing treatment time. After the RF treatment, indica and japonica rice (IR and JR) remained as A-type crystals, with the formation of an amylose-lipid complex. In contrast, the crystalline structure of waxy rice (WR) was disrupted. The RF treatment led to a decrease in crystallinity and short-range ordered structures. However, the DSC results indicated that the RF treatment enhanced the T, T, and T of IR and JR. The RF treatment resulted in an increase in the resistant starch (RS) of IR and JR, thereby reducing the digestibility. In addition, the pasting profiles of IR and JR after RF treatment were reduced with the increase in treatment time, while the RF-treated WR showed an opposite trend. The storage modulus (G') and loss modulus (G″) of all samples after the RF treatment obviously increased compared to the control.
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http://dx.doi.org/10.3390/foods11121723DOI Listing
June 2022

Simulated Reduced-Count Whole-Body FDG PET: Evaluation in Children and Young Adults Imaged on a Digital PET Scanner.

AJR Am J Roentgenol 2022 Jun 22. Epub 2022 Jun 22.

Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Digital PET scanners with increased sensitivity may allow shorter scan acquisitions or reduced administered radiopharmaceutical activities. To evaluate in children and young adults the impact of simulated shorter acquisition times on the quality of whole-body FDG PET images obtained using a digital PET/CT system. This retrospective study included 27 children and young adults (9 males, 18 females) who underwent clinically indicated whole-body FDG PET/CT examinations on a 25-cm axial FOV PET/CT system at 90 seconds per bed position. Raw list-mode data were reprocessed to simulate acquisition times of 60, 55, 50, 45, 40, and 30 seconds/bed. Three radiologists independently reviewed reconstructed images and assigned Likert scores for lesion conspicuity, normal structure conspicuity, image quality, and image noise. A separate observer recorded SUVmax, SUVmean, and SUVSD for liver, thigh, and the most FDG-avid lesion. SUVSD/SUVmean was calculated as a surrogate of image noise. ANOVA, Friedman's test, and Dunn's test were used to compare qualitative measures (combining reader scores) and SUV measurements. Mean age was 10.8±8.3 years, mean BMI was 18.7±2.9, and mean administered FDG activity was 4.4±0.4 MBq/kg (0.12±0.01 mCi/kg). No qualitative measure showed a significant difference versus 90 seconds/bed for the 60 seconds/bed simulated acquisition (all p>.05). Significant differences (all p<.05) versus 90 seconds/bed were observed for lesion conspicuity at ≤40 seconds/bed, conspicuity of normal structures and overall image quality at ≤45 seconds/bed, and image noise at ≤55 seconds/bed. SUVmean was not significantly different from 90 seconds/bed for any site for any reduced-count simulation (all p>.05). SUVSD/SUVmean and SUVmax showed gradual increases with decreasing acquisition times and were significantly different from 90 seconds/bed only for liver at 60 seconds/bed (SUVmax: 1.00±0.00 vs 1.05±0.03, p=.02; SUVSD/SUVmean: 0.09±0.02 vs 0.11±0.02, p=.04). Favorable findings for the simulated 60 seconds/bed acquisition suggest that, in children and young adults imaged on a 25-cm FOV digital PET scanner, acquisition time or administered FDG activity may be decreased by approximately 33% from the clinical standard without significantly impacting image quality. A 25-cm axial FOV digital scanner may allow performing FDG PET/CT examinations with reduced radiation exposure or faster scan times.
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http://dx.doi.org/10.2214/AJR.22.27894DOI Listing
June 2022

MicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake.

Nat Commun 2022 Jun 21;13(1):3545. Epub 2022 Jun 21.

State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 266071, Qingdao, People's Republic of China.

Pancreatic β cell dysfunction contributes to the pathogenesis of type 2 diabetes. MiR-21 has been shown to be induced in the islets of glucose intolerant patients and type 2 diabetic mice. However, the role of miR-21 in the regulation of pancreatic β cell function remains largely elusive. In the current study, we identify the pathway by which miR-21 regulates glucose-stimulated insulin secretion utilizing mice lacking miR-21 in their β cells (miR-21βKO). We find that miR-21βKO mice develop glucose intolerance due to impaired glucose-stimulated insulin secretion. Mechanistic studies reveal that miR-21 enhances glucose uptake and subsequently promotes insulin secretion by up-regulating Glut2 expression in a miR-21-Pdcd4-AP-1 dependent pathway. Over-expression of Glut2 in knockout islets results in rescue of the impaired glucose-stimulated insulin secretion. Furthermore, we demonstrate that delivery of miR-21 into the pancreas of type 2 diabetic db/db male mice is able to promote Glut2 expression and reduce blood glucose level. Taking together, our results reveal that miR-21 in islet β cell promotes insulin secretion and support a role for miR-21 in the regulation of pancreatic β cell function in type 2 diabetes.
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http://dx.doi.org/10.1038/s41467-022-31317-0DOI Listing
June 2022

An ultrapulsed CO laser combined with a long-pulsed Nd:YAG laser for the treatment of oral and maxillofacial pyogenic granuloma.

Dermatol Ther 2022 Jun 21:e15654. Epub 2022 Jun 21.

Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong, RP, China.

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http://dx.doi.org/10.1111/dth.15654DOI Listing
June 2022

Diselenide-crosslinked carboxymethyl chitosan nanoparticles for doxorubicin delivery: Preparation and in vivo evaluation.

Carbohydr Polym 2022 Sep 6;292:119699. Epub 2022 Jun 6.

Hospital of Chinese Traditional Medicine of Guangdong Province, Foshan 528000, Guangdong, PR China. Electronic address:

In this paper, we report a simple approach to fabricate diselenide-crosslinked carboxymethyl chitosan nanoparticles (DSe-CMC NPs) for doxorubicin (DOX) delivery, with disulfide analogs (DS-CMC NPs) as control. DS-CMC NPs and DSe-CMC NPs featured a spherical morphology and narrow size distribution with the average size about 200 nm. Carboxymethyl chitosan (CMC) as the starting material not only improved the biocompatibility of the nanocarriers but also enhanced physiological stability. Due to electrostatic interactions between DOX and CMC, the nanoparticles had high drug encapsulation efficiency (∼25 %). The nanoparticles disintegration and drug release were accelerated by the cleavage of diselenide bonds through oxidation by HO or reduction by GSH. In vitro cell experiments revealed that DOX-loaded DSe-CMC NPs possessed the highest drug accumulation and cytotoxicity in tumor cells. Moreover, DOX-loaded DSe-CMC NPs performed the enhanced growth inhibition in vivo than that of DS-CMC NPs. Thus, the diselenide-crosslinked nanoparticles possess great potentials for DOX delivery.
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http://dx.doi.org/10.1016/j.carbpol.2022.119699DOI Listing
September 2022

Starch-lauric acid complex-stabilised Pickering emulsion gels enhance the thermo-oxidative resistance of flaxseed oil.

Carbohydr Polym 2022 Sep 9;292:119715. Epub 2022 Jun 9.

School of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China; China-Singapore International Joint Research Institute, Guangzhou 511363, China; Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), Guangzhou 510640, China. Electronic address:

Hydrophobic-modified starch complexes have the potential to form Pickering emulsions and improve the oxidative stability of flaxseed oil. Here, V-type starch-lauric acid complexes (SLACs) were fabricated via solid encapsulation within 0.5-12 h and applied in flaxseed oil Pickering emulsions. Complexing index, X-ray diffraction and differential scanning calorimetry analyses confirmed that the degree of complexation increased with the reaction time. Pickering emulsion gels stabilised by SLACs generated with reaction times of 6 h and 12 h exhibited good storage stability and high yield stress, G' values and apparent viscosity. Confocal laser scanning microscopy and cryo-scanning electron microscopy revealed a gelation mechanism involving increased interface roughness and enhanced droplet-droplet interaction. In comparison to pure flaxseed oil, higher thermo-oxidative resistance was observed at 130 °C, with a markedly longer oxidation induction for emulsions and emulsion gels stabilised by SLACs. Our findings could assist in the design of hydrophobic-modified starch and provide a new paradigm for delaying oil oxidation.
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http://dx.doi.org/10.1016/j.carbpol.2022.119715DOI Listing
September 2022

Efficacy and Safety of Posterior Long-Segment Fixation Versus Posterior Short-Segment Fixation for Kummell Disease: A Meta-Analysis.

Geriatr Orthop Surg Rehabil 2022 13;13:21514593221107509. Epub 2022 Jun 13.

Second Clinical Medical School,Zhejiang Chinese Medical University, Hangzhou, China.

Purpose: Posterior short-segment fixation (SSF) and long-segment fixation (LSF) are two methods for the treatment of Kummell disease, but the safety and effectiveness of these two surgical methods still lack adequate medical evidence. This study aimed to evaluate the two methods.

Methods: Database searches for randomized controlled trials, case-control studies, and cohort studies of posterior SSF and posterior LSF in the treatment of Kummell disease were performed. After the document quality was evaluated with the Newcastle-Ottawa Quality Assessment Scale, a meta-analysis was carried out.

Results: Meta-analysis revealed that the operation time and intraoperative blood loss in the LSF group were higher than those in the SSF group [MD = -18.17, 95% CI (-30.31, -6.03), z = 2.93, = .003; MD = -82.07, 95% CI (-106.91, -57.24], z = 6.48, < .00001). The postoperative last follow-up local kyphosis angle in the SSF group was greater than that in the LSF group (MD = 3.18, 95% CI [.56, 5.81], z = 2.38, = .02), and there were no significant differences in perioperative complications, bone cement leakage rate, incidence of adverse events during follow-up, postoperative follow-up visual analog scale, postoperative Oswestry dysfunction index, and postoperative immediate local kyphosis angle between the two groups ( > .05).

Conclusion: SSF and LSF are effective and safe for the treatment of Kummell disease. SSF can reduce the operation time and intraoperative bleeding; LSF can better maintain the long-term stability of kyphosis. The methods should be evaluated by clinicians according to the individual situation of the patients.
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http://dx.doi.org/10.1177/21514593221107509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203950PMC
June 2022

Multimedia Tilt Photography-Assisted Remote Sensing Technology in Mine Ecological Restoration.

Comput Intell Neurosci 2022 10;2022:1442738. Epub 2022 Jun 10.

Lijiahao Coal Mine, National Energy Baotou Energy Co., Ltd, Ordos, Inner Mongolia Autonomous Region 017000, China.

Ecological restoration with the assistance of certain artificial measures is to restore the original ecological function and productivity of the ecosystem or to make the ecosystem develop to a virtuous circle, which is a complex systematic project. Based on this, combined with the actual needs of a mine ecological restoration project, this paper puts forward the technical process and method of quickly acquiring the geographic information of abandoned mines by using the oblique photography technology of unmanned aerial vehicles. The verification results show that the maximum plane/elevation residual error of the checkpoints measured in the field is 0.221 m-0.181 m, and the median error is 0.030 m-0.112 m. According to the encryption requirement of 1∶500 scale topographic mapping in hilly land, the plane position error of the inspection point relative to the field control point should be less than 0.175 m. The elevation should be less than 0.280 m, and the experimental results in this paper can meet the requirements. Oblique photography can provide abundant digital results, and it can play an important role in mine restoration scheme design, restoration construction, and monitoring and management after restoration.
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http://dx.doi.org/10.1155/2022/1442738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205708PMC
June 2022

The Effect of Complications on Oncological Outcomes of Colorectal Cancer Patients After Primary Surgery: A Propensity Score Matching Analysis.

Front Oncol 2022 3;12:857062. Epub 2022 Jun 3.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Purpose: The purpose of this study is to explore the oncologic outcomes of complications on colorectal cancer (CRC) patients who underwent primary surgery using a propensity score matching (PSM) analysis.

Methods: A retrospective study was conducted from Jan 2011 to Jan 2020 in a clinical center. The overall survival (OS) and disease-free survival (DFS) were compared among the no complications group, the major complications group and the minor complications group.

Results: A total of 4250 CRC patients who underwent radical primary surgery were included in the current study. Among them, 927 (21.8%) patients suffered complications. After 1:1 ratio PSM, there were 98 patients in the major complications group and in the minor complications group, and 911 patients in the overall complications group and in the no complications group. There was no significant difference in terms of baseline information after PSM (p>0.05). Complications were independent predictors of OS (p=0.000, HR=1.693, 95% CI=1.476-1.941) and DFS (p=0.000, HR=1.555, 95% CI=1.367-1.768). In terms of specific tumor stage, the no complications group had better OS on all stages (p=0.006) and stage III (p=0.003) CRC than the complications group after PSM. Furthermore, the no complications group had better DFS on all stages (p=0.005) and stage III (p=0.021) CRC than the complications group after PSM. However, there was no significant difference between the minor complications group and the major complications group in different tumor stages (p>0.05).

Conclusion: Complications were associated with poor prognosis of CRC and surgeons should be cautious of the adverse events.
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http://dx.doi.org/10.3389/fonc.2022.857062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203956PMC
June 2022

Research Methods in a Multinational Business Environment and Implications for Capital Formation: Application of Cross-Sectional Autoregressive Distributed Lag Methods.

Front Psychol 2022 1;13:867891. Epub 2022 Jun 1.

Department of Business Administration, Sukkur Institute of Business Administration University, Sukkur, Pakistan.

We explore whether foreign direct investment outflows augment or obstruct public or private capital in developing countries by decomposing domestic capital into private and public capital. While developed countries are the primary source of foreign direct investment outflows (FDIOs), developing economies have become the primary source of FDIO over the past 30 years. We apply cross-sectional autoregressive distributed lag (CS-ARDL) methods to overcome the issue of endogeneity and cross-sectional dependency in our dataset. This study analyzes the interaction effects of foreign direct investment and institutional quality (IQ) in promoting aggregate domestic capital formation in developing countries. Our empirical results show that FDI outflows augment private capital formation and additionally, IQ also upsurges private capital formation. Conversely, as per results, FDI outflows obstruct public capital formation, and IQ crowds out public capital formation significantly while private capital crowds out FDI inflows. As per result estimations, we notice that FDIO crowds in private capital formation, thus we conclude that the private sector controls the majority of the sectors for developing countries and the role of the public sector is quite minimal. We conclude that private and public capital possess different attributes; thus clubbing them together might result in aggregation bias. Our result estimations provide several useful policy implications.
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http://dx.doi.org/10.3389/fpsyg.2022.867891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202237PMC
June 2022

[Comparison of effectiveness between percutaneous coaxial large-channel endoscopic lumbar interbody fusion and minimal invasive transforaminal lumbar interbody fusion in treatment of degenerative lumbar spinal stenosis].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2022 Jun;36(6):681-690

Department of Orthopedics, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu Sichuan, 610041, P. R. China.

Objective: To compare the effectiveness of percutaneous coaxial large-channel endoscopic lumbar interbody fusion (PE-LIF) and minimal invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of degenerative lumbar spinal stenosis.

Methods: The clinical data of 134 patients with single-segment degenerative lumbar spinal stenosis who met the selection criteria between January 2019 and January 2021 were retrospectively analyzed, including 52 cases in PE-LIF group and 82 cases in MIS-TLIF group. There was no significant difference in general data such as gender, age, disease duration, surgical segment, and preoperative visual analogue scale (VAS) scores of low back pain and lower extremity pain, and Oswestry disability index (ODI) between the two groups ( >0.05). The operation time, intraoperative blood loss, postoperative drainage, hospitalization stay, and complications were recorded and compared between the two groups. The level of serum creatine kinase (CK) was recorded at 1 day before operation and at 1 and 3 days after operation to evaluate intraoperative muscle damage. The Brantigan criteria was used to evaluate the interbody fusion in the two groups. The VAS scores of low back pain and lower extremity pain at 1 day before operation and at 3 days, 3 months, and 1 year after operation, and the ODI scores at 1 day before operation and at 3 months and 1 year after operation were recorded and compared between the two groups.

Results: There was no significant difference in operation time and hospitalization stay between the two groups ( >0.05). The intraoperative blood loss and postoperative drainage in the PE-LIF group were significantly lower than those in the MIS-TLIF group ( <0.05). There was no significant difference in serum CK between the two groups before operation ( >0.05), and the serum CK in the PE-LIF group at 1 and 3 days after operation were significantly lower than those in the MIS-TLIF group ( <0.05). All patients were followed up regularly for 1 year. The postoperative VAS scores of low back pain and lower extremity pain and ODI score in both groups were significantly lower than those before operation ( <0.05); there was no significant difference between the two groups ( >0.05). At 1 year after operation, 48 patients in PE-LIF group had successful interbody fusion, and 77 patients in MIS-TLIF group had successful interbody fusion. There was no significant difference in the interbody fusion distribution between the two groups at 3 months and 1 year after operation ( >0.05). There were 2 and 3 cases of lower limb numbness, 1 and 3 cases of neuroedema pain, 1 and 1 case of Cage displacement, 1 and 1 case of pedicle screw loosening in the PE-LIF group and MIS-TLIF group, respectively. No infection or dural sac tearing occurred in the two groups. There was no significant difference in the incidence of complications between the two groups (9.6% 9.8%) ( =0.001, =0.979).

Conclusion: In the treatment of single-segment degenerative lumbar spinal stenosis, PE-LIF can achieve similar effectiveness as MIS-TLIF, and PE-LIF has less intraoperative blood loss and less muscle damage.
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http://dx.doi.org/10.7507/1002-1892.202202076DOI Listing
June 2022

[Analysis of technical advantages and disadvantages of percutaneous endoscopic lumbar interbody fusion and its trend prospect].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2022 Jun;36(6):653-659

Department of Spine Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou Guangdong, 510630, P. R. China.

Objective: To review and evaluate the technical advantages and disadvantages and research progress of percutaneous endoscopic lumbar interbody fusion.

Methods: The domestic and foreign related research literature on percutaneous endoscopic lumbar interbody fusion was extensively consulted. The advantages, disadvantages, and effectiveness were summarized. And the development trend of this technology was prospected.

Results: Compared with minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), percutaneous endoscopic lumbar interbody fusion has less intraoperative and postoperative bleeding, better improvement of low back pain in the early stage after operation, and similar long-term effectiveness, fusion rate, and incidence of complication, but a longer learning curve. The operation time of biportal and large-channel uniportal endoscopic lumbar fusion is close to that of MIS-TLIF, but the operation time of small-channel uniportal endoscopic fusion is longer than that of MIS-TLIF.

Conclusion: Percutaneous endoscopic lumbar interbody fusion has the advantages of less trauma and good effectiveness, but its learning curve is long, and indications should be strictly selected for this operation. In the future, with the continuous development and complementation of various endoscopic fusion technologies, this technology will gain better application prospects.
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http://dx.doi.org/10.7507/1002-1892.202202075DOI Listing
June 2022

Risk factors and consequences of conversion in minimally invasive distal pancreatectomy.

J Minim Access Surg 2022 Jul-Sep;18(3):384-390

Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Although recent studies have reported potential benefits of laparoscopic approach in distal pancreatectomy, reports of conversion during minimally invasive distal pancreatectomy (MIDP) were limited.

Methods: This was a retrospective study using data from Sir Run Run Shaw Hospital around May 2013 to December 2018. Outcomes of patients who had conversions during MIDP were compared with patients with successful MIDP and with patients undergoing open distal pancreatectomy (ODP).

Results: Two-hundred and eighty-three cases were included in this study: 225 (79.5%) had MIDP, 30 (10.6%) had conversions and 28 (9.9%) had outpatient department. The risk factors for conversion included large lesion size (heart rates [HR]: 5.632, 95% confidencevinterval [CI]: 1.036-1.450, P = 0.018) and pancreatic cancer (HR: 6.957, 95% CI: 1.359-8.022, P = 0.009). Compared with MIDP, those who required conversion were associated with longer operations (P = 0.003), higher blood loss (P < 0.001) and more severe of the complications (P < 0.001). However, no statistically significant differences were found between the conversion group and ODP.

Conclusions: Large lesion size and pancreatic cancer were reported to be independent risk factors for conversion during MIDP. As for post-operative outcomes, the outcomes of successfully MIDP were better than those for conversion. However, conversion did not lead to worsening outcomes when compared with ODP.
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http://dx.doi.org/10.4103/jmas.JMAS_4_20DOI Listing
June 2022

Publisher Correction: ILC1s control leukemia stem cell fate and limit development of AML.

Nat Immunol 2022 Jun 15. Epub 2022 Jun 15.

Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, USA.

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http://dx.doi.org/10.1038/s41590-022-01265-4DOI Listing
June 2022

Dysregulation of MiR-144-5p/RNF187 Axis Contributes To the Progression of Colorectal Cancer.

J Transl Int Med 2022 Mar 26;10(1):65-75. Epub 2022 Mar 26.

Department of Gastroenterology and Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China.

Background And Objectives: RING finger protein 187 (RNF187) belongs to RING domain-containing E3 ligases family, which was recently reported to be involved in oncogenesis and development of several cancers. This research aims to clarify the role of RNF187 in colorectal cancer (CRC) development.

Methods: The expression of RNF187 and miR-144-4p were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of RNF187 protein were assessed by western blot analysis. Cell Counting Kit-8 (CCK8) assay, clonogenic assay, cell scratch test and transwell assay were used to determine the proliferation, migration and invasion of CRC cells in vitro. The binding of miR-144-5p and RNF197 mRNA was validated by luciferase reporter assays. Tumor-bearing nude mice were used to determine CRC cells growth in vivo.

Results: RNF187 expression significantly increased in CRC specimens and cell lines compared to normal colon tissues and normal colonic mucosa cell line, respectively. Upregulation of RNF187 expression was inversely correlated to poor prognosis in CRC patients. In addition, knockdown of RNF187 expression inhibited the proliferation, migration, and invasion but promoted the apoptosis of CRC lines Caco-2 and SW480 cells. Further studies validated that RNF187 was the direct target of miR-144-5p. The expression of miR-144-5p was downregulated in CRC tissues, which was negatively correlated to the expression of RNF187. Restoration of miR-144-5p significantly inhibited the progression of CRC cells and its anti-tumor effects could be abrogated by overexpression of RNF187.

Conclusion: Our findings demonstrate the deregulation of miR-144-5p/ RNF187 axis in CRC, as well as its role in regulation of the tumor progression, thus providing a novel therapeutic strategy for CRC treatment.
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http://dx.doi.org/10.2478/jtim-2021-0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997807PMC
March 2022
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