Image harmonization: A review of statistical and deep learning methods for removing batch effects and evaluation metrics for effective harmonization.

Magnetic resonance imaging and computed tomography from multiple batches (e.g. sites, scanners, datasets, etc.) are increasingly used alongside complex downstream analyses to obtain new insights into the human brain. However, significant confounding due to batch-related technical variation, called batch effects, is present in this data; direct application of downstream analyses to the data may lead to biased results. Image harmonization methods seek to remove these batch effects and enable increased generalizability and reproducibility of downstream results. In this review, we describe and categorize current approaches in statistical and deep learning harmonization methods. We also describe current evaluation metrics used to assess harmonization methods and provide a standardized framework to evaluate newly-proposed methods for effective harmonization and preservation of biological information. Finally, we provide recommendations to end-users to advocate for more effective use of current methods and to methodologists to direct future efforts and accelerate development of the field.

Genetic susceptibility loci of lung cancer are associated with malignant risk of pulmonary nodules and improve malignancy diagnosis based on CEA levels.

Objective: The heightened prevalence of pulmonary nodules (PN) has escalated its significance as a public health concern. While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge, genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis. Yet, current understanding of the genetic loci associated with malignant PN (MPN) risk is limited. Methods: A frequency-matched case-control study was performed, comprising 247 MPN cases and 412 benign NP (BNP) controls. We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort. Loci associated with MPN risk were utilized to compute a polygenic risk score (PRS). This PRS was subsequently incorporated into the diagnostic evaluation of MPNs, with emphasis on serum tumor biomarkers. Results: Loci rs10429489G>A, rs17038564A>G, and rs12265047A>G were identified as being associated with an increased risk of MPNs. The PRS, formulated from the cumulative risk effects of these loci, correlated with the malignant risk of PNs in a dose-dependent fashion. A high PRS was found to amplify the MPN risk by 156% in comparison to a low PRS [odds ratio (OR)=2.56, 95% confidence interval (95% CI), 1.40-4.67]. Notably, the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen (CEA) in distinguishing MPNs from BPNs, with diagnostic values rising from 0.716 to 0.861 across low- to high-PRS categories. Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus. Conclusions: Loci rs10429489G>A, rs17038564A>G, and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.

Ferroportin 3 is a dual-targeted mitochondrial/chloroplast iron exporter necessary for iron homeostasis in Arabidopsis.

Mitochondria and chloroplasts are organelles with high iron demand that are particularly susceptible to iron-induced oxidative stress. Despite the necessity of strict iron regulation in these organelles, much remains unknown about mitochondrial and chloroplast iron transport in plants. Here, we propose that Arabidopsis ferroportin 3 (FPN3) is an iron exporter that is dual-targeted to mitochondria and chloroplasts. FPN3 is expressed in shoots, regardless of iron conditions, but its transcripts accumulate under iron deficiency in roots. fpn3 mutants cannot grow as well as the wild type under iron-deficient conditions and their shoot iron levels are lower compared with the wild type. Analyses of iron homeostasis gene expression in fpn3 mutants and inductively coupled plasma mass spectrometry (ICP-MS) measurements show that iron levels in the mitochondria and chloroplasts are increased relative to the wild type, consistent with the proposed role of FPN3 as a mitochondrial/plastid iron exporter. In iron-deficient fpn3 mutants, abnormal mitochondrial ultrastructure was observed, whereas chloroplast ultrastructure was not affected, implying that FPN3 plays a critical role in the mitochondria. Overall, our study suggests that FPN3 is essential for optimal iron homeostasis.

Voxel-wise intermodal coupling analysis of two or more modalities using local covariance decomposition.

When individual subjects are imaged with multiple modalities, biological information is present not only within each modality, but also between modalities - that is, in how modalities covary at the voxel level. Previous studies have shown that local covariance structures between modalities, or intermodal coupling (IMCo), can be summarized for two modalities, and that two-modality IMCo reveals otherwise undiscovered patterns in neurodevelopment and certain diseases. However, previous IMCo methods are based on the slopes of local weighted linear regression lines, which are inherently asymmetric and limited to the two-modality setting. Here, we present a generalization of IMCo estimation which uses local covariance decompositions to define a symmetric, voxel-wise coupling coefficient that is valid for two or more modalities. We use this method to study coupling between cerebral blood flow, amplitude of low frequency fluctuations, and local connectivity in 803 subjects ages 8 through 22. We demonstrate that coupling is spatially heterogeneous, varies with respect to age and sex in neurodevelopment, and reveals patterns that are not present in individual modalities. As availability of multi-modal data continues to increase, principal-component-based IMCo (pIMCo) offers a powerful approach for summarizing relationships between multiple aspects of brain structure and function. An R package for estimating pIMCo is available at: https://github.com/hufengling/pIMCo.

Endoscopic treatment can be a viable therapeutic option for esophageal gastrointestinal stromal tumors.

BACKGROUND: Esophageal gastrointestinal stromal tumors(GISTs) are extremely rare. We sought to determine whether endoscopic treatment can be a viable therapeutic option for esophageal GISTs. METHODS: A total of 20 cases with histological diagnosis of esophageal GISTs were obtained from our center between 2008 and 2020. Data on the clinicopathological features and treatment were recorded. RESULTS: There were 9 males (45%) and 11 females (55%) in this study, with a median age of 56 years. The tumors preferentially occurred in the middle and lower parts of the thoracic esophagus (45 and 40%, respectively). The mean size of the tumors was 2.27 cm and mitotic index was no more than 5/50 high power field (HPF) in all patients. In this study, 11 patients received endoscopic treatment and nine patients underwent surgical resection. Tumors ranged from 0.6 to 4 cm in the endoscopic treatment patients and 0.5 to 7 cm in the surgical patients. There were no significant differences in gender, age, symptoms, tumor location, tumor size, mitotic index, and adjuvant imatinib therapy between the endoscopic treatment group and the surgery group (all p > .05). The Kaplan-Meier curve suggested that there was also no significant difference in disease-free survival between the two groups (p = .264). CONCLUSIONS: Endoscopic treatment may be an option for the treatment of esophageal GISTs smaller than 5 cm with a mitotic index no more than 5/50 HPF.

Adeno-associated virus-based caveolin-1 delivery via different routes for the prevention of cholesterol gallstone formation.

BACKGROUND: Hepatic caveolin-1 (CAV1) is reduced in cholesterol gallstone disease (CGD). Mice with CAV1 deficiency were prone to develop CGD. However, it remains unknown whether restored hepatic CAV1 expression prevents the development of CGD. METHODS: C57BL/6 mice were injected with adeno-associated virus 2/8 (AAV2/8) vectors carrying the CAV1 gene (AAV2/8CAV1) via intravenous (i.v.) or intraperitoneal (i.p.) route and then subjected to a lithogenic diet (LD) for 8 weeks. Uninjected mice were used as controls. The functional consequences of rescuing CAV1 expression by either i.v. or i.p. AAV2/8CAV1 treatment for CGD prevention and its subsequent molecular mechanisms were examined. RESULTS: CAV1 expression was reduced in the liver and gallbladder of LD-fed CGD mice. We discovered that AAV2/8CAV1 i.p. delivery results in higher transduction efficiency in the gallbladder than tail vein administration. Although either i.v. or i.p. injection of AAV2/8CAV1 improved liver lipid metabolic abnormalities in CGD mice but did not affect LD feeding-induced bile cholesterol supersaturation. In comparison with i.v. administration route, i.p. administration of AAV2/8CAV1 obviously increased CAV1 protein levels in the gallbladder of LD-fed mice, and i.p. delivery of AAV2/8CAV1 partially improved gallbladder cholecystokinin receptor (CCKAR) responsiveness and impeded bile cholesterol nucleation via the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling, which induced a reduction in gallbladder mucin-1 (MUC1) and MUC5ac expression and gallbladder cholesterol accumulation. CONCLUSION: CGD prevention by i.p. AAV2/8CAV1 injection in LD-fed mice was associated with the improvement of gallbladder stasis, which again supported the notion that supersaturated bile is required but not sufficient for the formation of cholesterol gallstones. Additionally, AAV treatment via the local i.p. injection offers particular advantages over the systemic i.v. route for much more effective gallbladder gene delivery, which will be an excellent tool for conducting preclinical functional studies on the maintenance of normal gallbladder function to prevent CGD.

FGF15 promotes hepatic NPC1L1 degradation in lithogenic diet-fed mice.

BACKGROUND: Cholesterol gallstone disease (CGD) is accompanied by biliary cholesterol supersaturation. Hepatic Niemann-Pick C1-like 1 (NPC1L1), which is present in humans but not in wild-type (WT) mice, promotes hepatocyte cholesterol uptake and decreases biliary cholesterol supersaturation. In contrast, intestinal NPC1L1 promotes intestinal cholesterol absorption, increasing biliary cholesterol supersaturation. Ezetimibe (EZE) can inhibit both hepatic and intestinal NPC1L1. However, whether hepatic NPC1L1 can affect CGD progress remains unknown. METHODS: Mice expressing hepatic NPC1L1 (NPC1L1hepatic-OE mice) were generated using Adeno-associated viruses (AAV) gene delivery. The protein level and function of hepatic NPC1L1 were examined under chow diet, high fat-cholesterol diet (HFCD), and lithogenic diet (LD) feeding. Gallstone formation rates were examined with or without EZE treatment. Fibroblast growth factor 15 (FGF15) treatment and inhibition of fibroblast growth factor receptor 4 (FGFR4) were applied to verify the mechanism of hepatic NPC1L1 degradation. RESULTS: The HFCD-fed NPC1L1hepatic-OE mice retained the biliary cholesterol desaturation function of hepatic NPC1L1, whereas EZE treatment decreased biliary cholesterol saturation and did not cause CGD. The ubiquitination and degradation of hepatic NPC1L1 were discovered in LD-fed NPC1L1hepatic-OE mice. Treatment of FGF15 during HFCD feeding and inhibition of FGFR4 during LD feeding could affect the protein level and function of hepatic NPC1L1. CONCLUSIONS: LD induces the ubiquitination and degradation of hepatic NPC1L1 via the FGF15-FGFR4 pathway. EZE may act as an effective preventative agent for CGD.

The Effect of the No Pain Labor & Delivery-Global Health Initiative on Cesarean Delivery and Neonatal Outcomes in China: An Interrupted Time-Series Analysis.

BACKGROUND: The proportion of live births by cesarean delivery (CD) in China is significant, with some, particularly rural, provinces reporting up to 62.5%. The No Pain Labor & Delivery-Global Health Initiative (NPLD-GHI) was established to improve obstetric and neonatal outcomes in China, including through a reduction of CD through educational efforts. The purpose of this study was to determine whether a reduction in CD at a rural Chinese hospital occurred after NPLD-GHI. We hypothesized that a reduction in CD trend would be observed. METHODS: The NPLD-GHI program visited the Weixian Renmin Hospital, Hebei Province, China, from June 15 to 21, 2014. The educational intervention included problem-based learning, bedside teaching, simulation drill training, and multidisciplinary debriefings. An interrupted time-series analysis using segmented logistic regression models was performed on data collected between June 1, 2013 and May 31, 2015 to assess whether the level and/or trend over time in the proportion of CD births would decline after the program intervention. The primary outcome was monthly proportion of CD births. Secondary outcomes included neonatal intensive care unit (NICU) admissions and extended NICU length of stay, neonatal antibiotic and intubation use, and labor epidural analgesia use. RESULTS: Following NPLD-GHI, there was a level decrease in CD with an estimated odds ratio (95% confidence interval [CI]) of 0.87 (0.78-0.98), P = .017, with odds (95% CI) of monthly CD reduction an estimated 3% (1-5; P < .001), more in the post- versus preintervention periods. For labor epidural analgesia, there was a level increase (estimated odds ratio [95% CI] of 1.76 [1.48-2.09]; P < .001) and a slope decrease (estimated odds ratio [95% CI] of 0.94 [0.92-0.97]; P < .001). NICU admissions did not have a level change (estimated odds ratio [95% CI] of 0.99 [0.87-1.12]; P = .835), but the odds (95% CI) of monthly reduction in NICU admission was estimated 9% (7-11; P < .001), greater in post- versus preintervention. Neonatal intubation level and slope changes were not statistically significant. For neonatal antibiotic administration, while the level change was not statistically significant, there was a decrease in the slope with an odds (95% CI) of monthly reduction estimated 6% (3-9; P < .001), greater post- versus preintervention. CONCLUSIONS: In a large, rural Chinese hospital, live births by CD were lower following NPLD-GHI and associated with increased use of labor epidural analgesia. We also found decreasing NICU admissions. International-based educational programs can significantly alter practices associated with maternal and neonatal outcomes.

Patient and Provider Perceptions of a Patient Navigation Program to Improve Postpartum Care Among Publicly Insured Women.

OBJECTIVE: This study was aimed to assess patient and provider perceptions of a postpartum patient navigation program. STUDY DESIGN: This was a mixed-method assessment of a postpartum patient navigation program. Navigating New Motherhood (NNM) participants completed a follow-up survey including the Patient Satisfaction with Interpersonal Relationship with Navigator (PSN-I) scale and an open-ended question. PSN-I scores were analyzed descriptively. Eighteen provider stakeholders underwent in-depth interviews to gauge program satisfaction, perceived outcomes, and ideas for improvement. Qualitative data were analyzed by the constant comparative method. RESULTS: In this population of low-income, minority women, participants (n = 166) were highly satisfied with NNM. The median PSN-I score was 45 out of 45 (interquartile range [IQR]: 43-45), where a higher score corresponds to higher satisfaction. Patient feedback was also highly positive, though a small number desired more navigator support. Provider stakeholders offered consistently positive program feedback, expressing satisfaction with NNM execution and outcomes. Provider stakeholders noted that navigators avoided inhibiting clinic workflow and eased clinic administrative burden. They perceived NNM improved multiple clinical and satisfaction outcomes. All provider stakeholders believed that NNM should be sustained long-term; suggestions for improvement were offered. CONCLUSION: A postpartum patient navigation program can perceivably improve patient satisfaction, clinical care, and clinic workflow without burden to clinic providers.

Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones.

BACKGROUND: Cholesterol gallstones account for over 80% of gallstones, and the pathogenesis of gallstone formation involves genetic and environmental factors. However, data on the evolution of cholesterol gallstones with various densities are limited. This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis. METHODS: Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones. The relative abundance of microbiota in gallbladder tissues was detected. Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1, MUC2, MUC3a, MUC3b, MUC4, MUC5ac and MUC5b in gallbladder tissues and bile. The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression. RESULTS: A total of 23 patients with gallbladder stones were included. The density of gallstones in the isodense group was significantly lower than that of the calcified group (34.20 ± 1.50 vs. 109.40 ± 3.84 HU, P < 0.0001). Compared to the isodense group, the calcified group showed a higher abundance of gram-positive bacteria at the fundus, in the body and neck of gallbladder tissues. The concentrations of MUC1, MUC2, MUC3a, MUC3b, MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups, while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus (15.49 ± 0.69 vs. 10.23 ± 0.54 ng/mL, P < 0.05), in the body (14.54 ± 0.94 vs. 11.87 ± 0.85 ng/mL, P < 0.05) as well as in the neck (14.77 ± 1.04 vs. 10.85 ± 0.72 ng/mL, P < 0.05) of gallbladder tissues. Moreover, the abundance of bacteria was positively correlated with the expression of MUC4 (r = 0.569, P < 0.05) in the calcified group. CONCLUSIONS: This study showed the potential clinical relevance among biliary microbiota, mucins and calcified gallstones in patients with gallstones. Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.

"Real-world" effect of a peer counselor on breastfeeding outcomes in an urban prenatal clinic in the United States.

BACKGROUND: One approach for improving breastfeeding support and alleviating breastfeeding disparities is the implementation of a clinic-based peer counselor. Our objective was to assess the "real life" effects of an autonomous peer counselor who provides tailored support to low-income, minority women based on individual needs rather than a pre-determined research protocol. METHODS: This is a secondary analysis of a prospective cohort study of women receiving publicly funded prenatal care during the 6 months before and after introduction of a peer counselor in a single prenatal clinic. The peer counselor provided one-on-one antenatal and postpartum lactation support. Electronic medical record and survey data were collected. The primary outcome was breastfeeding continuation at 6 weeks postpartum. Secondary outcomes included breastfeeding comfort, confidence, and training satisfaction, any breastfeeding, and total breastfeeding duration. Bivariable and multivariable analyses were performed. RESULTS: Peer counselor exposure was not associated with the primary outcome of continued breastfeeding at 6 weeks (55.6% with peer counselor versus 49.1% without; aOR 1.26, 95% CI 0.69-2.31). However, women with peer counselor exposure were more likely to be satisfied with breastfeeding training at the time of delivery (98.2% vs. 83.6%, p = 0.006) and were more likely to have performed any breastfeeding (89.8% vs. 78.9%, p = 0.04), which remained significant on multivariable analysis (aOR 2.85, 95% CI 1.11-7.32). CONCLUSIONS: Peer counselor interventions are a promising approach to increase breastfeeding initiation. Further research is required to inform the most efficacious approach while also allowing peer counselors to operate independently and in line with the specific needs of their clients.

Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo.

Mediator of DNA damage checkpoint protein 1 (MDC1) is involved in DNA damage repair and has been linked to tumor invasion, metastasis, and prognosis. This study investigated the effects of MDC1 in oral squamous cell carcinoma (OSCC) in vitro and in vivo. RNA interference-mediated knockdown of MDC1 was performed in two OSCC cell lines (Tca-8113 and KB). Real-time PCR and western blotting were performed to determine expression of mRNA and protein, respectively, of MDC1. Cell viability was assessed using the MTT assay. Colony-formation assays were performed by staining with 0.5% crystal violet. Cell migration and invasion were detected by Transwell assays. The role of MDC1 in OSCC was examined in vivo via injection of Tca-8113 cells transfected with MDC1 small interfering (si)RNA or negative-control siRNA into a mouse xenograft model of OSCC. Our results showed that MDC1 knockdown decreased cell proliferation. Inhibition of MDC1 decreased colony formation of Tca-8113 and KB cells by 62% and 68%, respectively, and MDC1 knockdown reduced the number of migratory and invasive cells compared with the control group. Moreover, the xenograft mouse model of MDC1 knockdown showed reduced tumor growth. Our study suggests that MDC1 plays a role in tumorigenesis and might be a potential target for the treatment of patients with OSCC.

Investigating the anatomical relationship between the maxillary molars and the sinus floor in a Chinese population using cone-beam computed tomography.

BACKGROUND: The anatomical relationship between the root apices of maxillary molars and the maxillary sinus floor (MSF) is important for the treatment of dental implantations and endodontic procedures. In this study, the detailed anatomical relationships between the root apices of maxillary molars and the MSF were studied in a Chinese population using CBCT. METHODS: We collected the CBCT data files of patients who visited the stomatology outpatient clinic in Shanghai Fifth People's Hospital, Fudan University from January 1, 2017 to January 1, 2019 and measured the following items: the distance between the molar root apices and the MSF, the thickness of the mucosa and cortical bone of the MSF closest to the root apices, and the angle between the buccal and palatal roots. RESULTS: The shortest distances between the root apices and the MSF were 1.57 ± 3.33 mm (the mesiobuccal root of the left second molar) and 1.61 ± 3.37 mm (the mesiobuccal root of the right second molar). Apical protrusion over the inferior wall of the sinus most often occurred in the mesiobuccal root of left second molar (frequency, 20.5%). The mucosa of the MSF was thinnest at the distobuccal root of the right second molar (1.52 ± 0.85 mm), the cortical bone of the MSF was thinnest at the mesiobuccal root of the right second molar (0.46 ± 0.28 mm), and the angle between the buccal and palatal roots ranged from 12.01° to 124.2° (42.36 ± 24.33 °). CONCLUSIONS: Among the root apices of the maxillary molars, the mesiobuccal root apex of the left second molar was closest to the MSF, and it had the highest incidence of protrusion into the sinus. The unique anatomical relationship between the maxillary molars and the MSF in this Chinese population is critical for treatment planning for dental implantation or endodontic procedures.

Hepatitis C Virus Infection Is Positively Associated with Gallstones in Liver Cirrhosis.

AIM: To elucidate the prevalence and risk factors of gallstone disease (GD) among patients with liver disease and explore their association with the aetiology and severity of hepatic injury. METHODS: We analysed 4,832 subjects of hepatic injury induced by one of the following aetiologies: hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, excessive alcohol consumption. The risk factors significantly associated with GD were analysed using stepwise logistic regression analysis, the influence of aetiology and severity of liver disease on the prevalence of GD were assessed by multiple logistic regression analysis adjusting for confounding factors. RESULTS: Three thousand forty eight patients were of positive HBV surface antigen alone with a prevalence of GD of 18.6%, 526 were tested as positive Anti-HCV alone with a prevalence of GD of 22.4%, and 1,258 were identified with excessive alcohol consumption patterns with a prevalence of GD of 13.5%. In each aetiological category, the prevalence of GD increased by age. Stepwise logistic regression analysis showed that age, female, low-density lipoprotein-cholesterol (LDL-Cho), family history of GD, HBV infection, HCV infection, chronic hepatitis and cirrhosis were independent factors associated with GD. After adjusting for age, LDL-Cho and family history of GD, the prevalence of gallstone disease was significantly associated with HCV-related cirrhosis in both genders, HBV-related cirrhosis in males and alcohol-related cirrhosis in females compared with patients with less severe liver disease [corrected]. After adjusting for gender, age, LDL-Cho and family history of GD, patients with HCV-related cirrhosis (OR 2.66, 95% CI 1.49-3.84) but not HBV-related cirrhosis (OR 1.52, 95% CI 0.73-1.82) were more likely to have GD compared with alcohol-related cirrhosis. CONCLUSION: HCV infection is positively associated with gallstone formation especially in those with cirrhosis patients.

No Pain Labor & Delivery: A Global Health Initiative's Impact on Clinical Outcomes in China.

The availability of labor analgesia is highly variable in the People's Republic of China. There are widespread misconceptions, by both parturients and health care providers, that labor epidural analgesia is harmful to mother and baby. Meanwhile, China has one of the highest cesarean delivery rates in the world, exceeding 50%. The goal of the nongovernmental No Pain Labor & Delivery (NPLD) is to facilitate sustainable increases in vaginal delivery rates by increasing access to safe neuraxial labor analgesia, thereby decreasing the cesarean delivery rate. NPLD was launched in 2008 with the stated goal of improving labor outcome in China by increasing the absolute labor epidural analgesia rate by 10%. NPLD established 10 training centers over a 10-year period. We hypothesized that increased availability of labor analgesia would result in reduced requests for cesarean delivery and better labor outcomes for mother and baby. Multidisciplinary teams of Western clinicians and support staff traveled to China for 8 to 10 days once a year. The approach involved establishing 24/7 obstetric anesthesia coverage in Chinese hospitals through education and modeling multidisciplinary approaches, including problem-based learning discussions, bedside teaching, daily debriefings, simulation training drills, and weekend conferences. As of November 2015, NPLD has engaged with 31 hospitals. At 24 of these sites, 24/7 obstetric anesthesia coverage has been established and labor epidural analgesia rates have exceeded 50%. Lower rates of cesarean delivery, episiotomy, postpartum blood transfusion, and better neonatal outcomes were documented in 3 impact studies comprising approximately 55,000 deliveries. Changes in practice guidelines, medical policy, and billing codes have been implemented in conjunction with the modernization of perinatal practice that has occurred concurrently in China since the first NPLD trip in 2008.

Porous structure design and properties of dental implants.

At present, selective laser melting (SLM) 3D printing technology can accurately control the internal pore structure and complex cell shape. Three types of reticulated meshes with cubic, G7 and composite structure cell shapes were fabricated by the SLM 3D printing technology using Ti-6Al-4V alloy powders. The bone stresses around the implant and the stresses in the implant were analyzed by ANSYS finite element software, which comprehensively evaluated the effect of porous dental implants with different spatial porosity characteristics on osseointegration. The results show that porous dental implants with composite structure of pore characteristics have improved mechanical and biological properties and can better promote the growth and integration of bone tissue.

Effect of angled abutments in the posterior maxillary region on tilted implants: a 3D finite element analysis.

The aim of this study was to evaluate the bone tissue effects under dynamic loading using finite element analysis (FEA) for four angled abutments with different deviated palatal lateral tilt angles. A three-dimensional model of the posterior maxillary region and an implant crown model were reconstructed and assembled with a three-dimensional model of the implant, angled abutment, and central screw to create a total of 10 three-dimensional finite element models tilted at 15 ∘ , 20 ∘ , 25 ∘ , and 30 ∘ in three groups, and the dynamic loads simulating oral mastication were loaded on the implant crown to analyze the equivalent stresses and strains in the peri-implant bone tissues. Under the dynamic loading, the cortical bone on the buccal side of the implant neck showed different degrees of stress concentration, and the cortical bone stress was much higher than the cancellous bone, and the strain concentration area of each model was located in the bone tissue around the implant neck and base. For the use of angular abutment, under the premise that the cortical bone stresses and strains of the 10 models meet the requirements for use, the peak stresses of 2.907 MPa, 3.018 MPa, and 2.164 MPa were achieved by using the 20 ∘ angular abutment to achieve the tilt angles of 20 ∘ , 25 ∘ , and 30 ∘ implantation, which is more advantageous compared with other models.

Finite Element Analysis of Stress Distributions for Mandibular Dental Implant-Supported Overdentures with Magnetic Attachments in Osteoporotic and Normal Bone.

PURPOSE: To compare the biomechanical responses of a normal mandible to an osteoporotic mandible with two-implant-supported magnetic attachments. MATERIALS AND METHODS: A 3D finite-element model of a two-implant-supported mandibular overdenture with magnetic attachments was developed, and normal and osteoporotic bone samples were prepared. Four types of load were applied to the overdenture in each model: 100 N vertical and oblique loads on the right first molar, and a 100 N vertical load on the right canine and incisors. Biomechanical behaviors of the peri-implant bone, implant, and mucosa were recorded. Maximum equivalent stresses and elastic strains were analyzed. RESULTS: Equivalent elastic strain in osteoporotic cortical and cancellous bone was 9% to 71% and was 142% and 207% greater than in normal cortical bone, respectively. Equivalent elastic strain in the first molar oblique loading condition was 101% to 190% greater than in the first molar vertical loading condition. CONCLUSIONS: Osteoporotic cancellous bone was weaker and less resistant to deformation than normal bone, and oblique loading was more harmful than vertical loading.

Single-cell RNA sequencing reveals aberrant sphingolipid metabolism in non-small cell lung cancer impacts tumor-associated macrophages and stimulates angiogenesis via macrophage inhibitory factor signaling.

BACKGROUND: Sphingolipids not only serve as structural components for maintaining cell membrane fluidity but also function as bioactive molecules involved in cell signaling and the regulation of various biological processes. Their pivotal role in cancer cell development, encompassing cancer cell proliferation, migration, angiogenesis, and metastasis, has been a focal point for decades. However, the contribution of sphingolipids to the complexity of tumor microenvironment promoting cancer progression has been rarely investigated. METHODS: Through the integration of publicly available bulk RNA-seq and single-cell RNA-seq data, we conducted a comprehensive analysis to compare the transcriptomic features between tumors and adjacent normal tissues, thus elucidating the intricacies of the tumor microenvironment (TME). RESULTS: Disparities in sphingolipid metabolism (SLM)-associated genes were observed between normal and cancerous tissues, with the TME characterized by the enrichment of sphingolipid signaling in macrophages. Cellular interaction analysis revealed robust communication between macrophages and cancer cells exhibiting low SLM, identifying the crucial ligand-receptor pair, macrophage inhibitory factor (MIF)-CD74. Pseudo-time analysis unveiled the involvement of SLM in modulating macrophage polarization towards either M1 or M2 phenotypes. Categorizing macrophages into six subclusters based on gene expression patterns and function, the SPP1+ cluster, RGS1+ cluster, and CXCL10+ cluster were likely implicated in sphingolipid-induced M2 macrophage polarization. Additionally, the CXCL10+, AGER+, and FABP4+ clusters were likely to be involved in angiogenesis through their interaction with endothelial cells. CONCLUSION: Based on multiple scRNA-seq datasets, we propose that a MIF-targeted strategy could potentially impede the polarization from M1 to M2 and impair tumor angiogenesis in low-SLM non-small cell lung cancer (NSCLC), demonstrating its potent antitumor efficacy.

Mechanical and modal analysis of different implant strategies for loss of three teeth with bone atrophy in the maxillary posterior region.

PURPOSE: This study aimed to evaluate the stress distribution and secondary stability involved in five implant strategies, including implant-supported prostheses (ISP) and tooth-implant-supported prostheses (TISP), used for bone atrophy in the maxillary posterior region with teeth loss using finite element analysis, and to explore the more desirable implant methods. METHODS: Five implant strategies were made to analyze and compare: M1, implant-supported prosthesis consisting of a short implant with a regular implant; M2, implant-supported prosthesis consisting of a tilted implant with a regular implant; M3, cantilever structure; M4, tooth-implant-supported prosthesis consisting of a short implant with a regular implant; M5, tooth-implant-supported prosthesis consisting of a regular implant, and M6, with only the natural teeth as a control group. Dynamic loading of the above models was performed in finite element analysis software to assess the stress distribution of the bone tissue and implants using the von Mise criterion. Finally, the secondary stability of different models was evaluated by modal analysis. RESULTS: The maximum stress distribution in the cortical bone in M1(60 MPa) was smaller than that in M2(97 MPa) and M3(101 MPa), The first principal strain minimum was obtained in M2 (2271µÎµ). M4 (33 MPa, 10085 Hz) with the best mechanical properties and highest resonance frequency. But increased the loading on the natural teeth. CONCLUSIONS: Short implants and tilted implants are both preferred implant strategies, if cantilever construction is necessary, a tooth-implant-supported prosthesis consisting of a short implant and a regular implant is recommended.