A follow-up study on the recovery and reinfection of Omicron COVID-19 patients in Shanghai, China.

Limited follow-up data is available on the recovery of Omicron COVID-19 patients after acute illness. It is also critical to understand persistence of neutralizing antibody (NAb) and of T-cell mediated immunity and the role of hybrid immunity in preventing SARS-CoV-2 reinfection. This prospective cohort study included Omicron COVID-19 individuals from April to June 2022 in Shanghai, China, during a large epidemic caused by the Omicron BA.2 variant. A total of 8945 patients from three medical centres were included in the follow up programme from November 2022 to February 2023. Of 6412 individuals enrolled for the long COVID analysis, 605 (9.4%) individuals experienced at least one sequelae, mainly had fatigue and mental symptoms specific to Omicron BA.2 infection compared with other common respiratory tract infections. During the second-visit, 548 (12.1%) cases of Omicron reinfection were identified. Hybrid immunity with full and booster vaccination had reduced risk of SARS-CoV-2 reinfection by 0.29-fold (95% CI: 0.63-0.81) and 0.23-fold (95% CI: 0.68-0.87), respectively. For 469 participants willing to the hospital during the first visit, those who received full (72 [IQR, 36-156]) or booster (64 [IQR, 28-132]) vaccination had significantly higher neutralizing antibody titers than those with incomplete vaccination (36 [IQR, 16-79]). Moreover, non-reinfection cases had higher neutralizing antibody titers (64 [IQR, 28-152]) compared to reinfection cases (32 [IQR, 20-69]).

Risk factors associated with loss of variable-thread tapered implants: A retrospective observational study of 1-5 years.

OBJECTIVES: This study aimed to evaluate the survival rate of variable-thread tapered implants (VTTIs) and identify risk factors for early/late implant loss. MATERIALS AND METHODS: From January 2016 to December 2019, patients who received VTTIs were included in this study. The cumulative survival rates (CSRs) at implant/patient levels were calculated by the life table method and presented via Kaplan-Meier survival curves. The relation between investigated variables and early/late implant loss was analyzed by the multivariate generalized estimating equation (GEE) regression model on the implant level. RESULTS: A total of 1528 patients with 2998 VTTIs were included. 95 implants from 76 patients were lost at the end of observation. At the implant level, the CSRs at 1, 3, and 5 years were 98.77%, 96.97%, and 95.39%, respectively, whereas they were 97.84%, 95.31%, and 92.96% at the patient level, respectively. The multivariate analysis revealed that non-submerged implant healing (OR = 4.63, p = .037) was associated with the early loss of VTTIs. Besides, male gender (OR = 2.48, p = .002), periodontitis (OR = 3.25, p = .007), implant length <10 mm (OR = 2.63, p = .028), and overdenture (OR = 9.30, p = .004) could significantly increase the risk of late implant loss. CONCLUSION: Variable-thread tapered implants could reach an acceptable survival rate in clinical practice. Non-submerged implant healing was associated with early implant loss; male gender, periodontitis, implant length <10 mm, and overdenture would significantly increase the risk of late implant loss.

Responses of Sinus Membrane and Antral Pseudocyst Following Lateral Window Sinus Augmentation with Bone Grafting: A Retrospective Study.

PURPOSE: To investigate the influence of lateral window sinus augmentation on sinus physiology, including sinus membrane thickness and the outcome of antral pseudocysts. MATERIALS AND METHODS: This retrospective study was performed by reviewing all lateral window sinus augmentation procedures, which were done between the years 2013 and 2015. Each enrolled patient had CBCT images preoperatively (T0), immediately postoperatively (T1), and 6 months postoperatively (T2). The sinus membrane thickness, pseudocyst dimensions, and intraoperative perforation were evaluated. Patient-related factors such as age and sex that could influence the mucosal properties were also analyzed. RESULTS: Based on established inclusion criteria, 306 patients with 320 sinuses were included in this study. The overall mean thickness of the sinus membrane (T0) was 1.30 ± 1.08 mm, and membrane thickening (> 2 mm) was observed in 22.19% of the sinuses. Preexisting pseudocysts were identified in 24 sinuses (7.50%), most of which remained unchanged or disappeared after 6 months. The intraoperative membrane perforation rate was lowest (1.96%) when the membrane thickness was 1.0 to 1.5 mm, and the perforation rate was increased in patients with thickened (> 2 mm) or thinned (≤ 1 mm) membrane. Membranes swelled immediately after operation (T1 vs T0, P < .01) and gradually recovered at 6 months. No significant change in membrane thickness was shown after the sinus augmentation procedure in the perforation group and pseudocyst group. The mean thickness of the sinus membrane at T0 and T1 was significantly higher for male subjects (P < .01). CONCLUSION: Lateral window sinus augmentation has little or no impact on sinus membrane thickness and antral pseudocysts after a 6-month healing period, except for a transient mild membrane swelling. Thickened and thinned membrane were risk factors for intraoperative perforation. Small-sized perforation and pseudocysts might not contraindicate sinus augmentation from the standpoint of the surgical impact on the sinus membrane.

A novel neoantigen discovery approach based on chromatin high order conformation.

BACKGROUND: High-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate the immune response of the T cell. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response. METHODS: Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Based on our previous discoveries, we propose to investigate the distribution of neoantigens with different immunogenicity abilities in 3D genome and propose to adopt this important information into neoantigen prediction. RESULTS: We retrospect the DNA origins of the immuno-positive and immuno-negative neoantigens in the context of 3D genome and discovered that DNA loci of the immuno-positive neoantigens and immuno-negative neoantigens have very different distribution pattern. Specifically, comparing to the background 3D genome, DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We thus used this information into neoantigen prediction and demonstrated the effectiveness of this approach. CONCLUSION: We believe that the 3D genome information will help to increase the precision of neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

The optimization of sintering treatment on bovine-derived bone grafts for bone regeneration: in vitro and in vivo evaluation.

Modifications of sintering temperature and treatment time of bovine-derived bone grafts affect their physicochemical properties and further influence biological activity. Three different temperature sintered bovine-derived bone grafts: group I (300 °C 3 h), group II (300 °C 3 h plus 530 °C 6 h), and group III (300 °C 3 h plus 1000 °C 2 h) and Bio-Oss® were characterized and then compared in vitro for their effects on bone marrow stromal cells (BMSCs) migration, proliferation, and differentiation as estimated by cell migration assay, Alkaline phosphatase (ALP) activity assay, and Alizarin red staining. Further, the four bone grafts were implanted into the calvarial defects of rabbits to evaluate bone regeneration and graft degradation. The four deproteinized bovine-derived bone grafts displayed different surface topography. Group II displayed the highest potential of attracting cells. Both groups I and II markedly promote BMSCs differentiation. After 6 and 12 weeks, defects grafted with groups I and II displayed a significant higher bone fraction than defects grafted with group III and Bio-Oss®. Bone graft remnants remained in all four groups. Taken together, sintering at 300 °C for 3 h and sintering at 300 °C for 3 h with an addition of 530 °C for 6 h of bovine-dervied bone grafts displayed potential use in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:272-281, 2020.

Refolding Dynamics of gp41 from Pre-fusion to Pre-hairpin States during HIV-1 Entry.

The HIV-1 infection is triggered by the binding of the viral envelope glycoprotein (Env) gp120-gp41 trimer to host-cell receptor CD4 and co-receptor CCR5/CXCR4, which leads to substantial conformational changes of Env, that is, structural transition of gp120 from a closed to an open state followed by gp41 refolding from pre-fusion to post-fusion states. The latter finally promotes membrane fusion, likely via visiting a critical pre-hairpin state of gp41. The complete conformational dynamics of the pre-hairpin formation at atomic resolution, however, is still unknown. Here, by constructing a Markov state model based on the all-atom molecular dynamics (MD) with an aggregated simulation time of ∼24 µs, we reveal the gp41 refolding dynamics from pre-fusion to pre-hairpin state and the key metastable states involved. Moreover, we further explored the drug resistance mechanism of two C-terminal heptad repeat-derived gp41 inhibitors, T20 and sifuvirtide, based on the constructed inhibitor-bound gp41 pre-hairpin complexes. The results indicate that these two inhibitors have distinct binding sites on gp41 but share a common drug resistance region that usually exhibits a helical structure in the pre-hairpin state yet adopts various secondary structures in other metastable states. Moreover, we conducted several mutant MD simulations to further investigate the mechanisms of how some drug-resistant mutations might affect the pre-hairpin formation, which in turn prevent the inhibitor recognition. Our findings provide deep structural insights into the molecular mechanisms of the pre-hairpin formation for gp41, which helps to guide future anti-HIV drug design.

Opening dynamics of HIV-1 gp120 upon receptor binding is dictated by a key hydrophobic core.

HIV-1 entry is mediated firstly by the molecular recognition between the viral glycoprotein gp120 and its receptor CD4 on host T-cells. As a key antigen that can be targeted by neutralizing antibodies, gp120 has been a focus for extensive studies with efforts to understand its structural properties and conformational dynamics upon receptor binding. An atomistic-level revelation of gp120 opening dynamics activated by CD4, however, is still unknown. Here, by constructing a Markov State Model (MSM) based on hundreds of Molecular Dynamics (MD) simulations with an aggregated simulation time of ∼20 microseconds (µs), we identify the key metastable states of gp120 during its opening dynamics upon CD4 binding. The MSM provides a clear dynamic model whereby the identified metastable states coexist and can reach an equilibrium. More importantly, a hydrophobic core flanked by variable loops (V1V2 and V3) and the ß20/21 region plays an essential role in triggering the gp120 opening. Any destabilizing effects introduced into the hydrophobic core, therefore, can be expected to promote transition of gp120 to an open state. Moreover, the variable loops demonstrate high flexibilities in fully open gp120. In particular, the V3 region is capable of exploring both closed and open conformations, even with the V1/V2 loops largely adopting an open form. In addition, the bridging sheet formation in gp120 is likely induced by the incoming co-receptor/antibody recognitions, since the V1/V2 structure is highly heterogeneous so that the bridging-sheet formed conformation is not the most populated state. Our studies provide deep insights into the dynamic features of gp120 and its molecular recognitions to the broadly neutralizing antibodies, which guides future attempts to design more effective gp120 immunogens.

Strontium-incorporated titanium implant surface treated by hydrothermal reactions promotes early bone osseointegration in osteoporotic rabbits.

OBJECTIVES: The aim of the present study was to investigate the effects of strontium-modified implant surfaces on promoting early bone osseointegration in osteoporotic rabbits. MATERIALS AND METHODS: The surface topographies, chemical elements, contact angles and ionic releases of the SLA and SLA-Sr samples were analysed by special instruments separately. Sixteen ovariectomized New Zealand rabbits received glucocorticoid administration, and sixteen SHAM rabbits were used as controls. After generating a successful osteoporosis-induced model, SLA and SLA-Sr implants were randomly inserted into the tibia and femur metaphysis of each animal. The rabbits were sacrificed after 3 and 6 weeks of bone healing, and then, removal torque values (RTVs), percentage of bone area (BA%) and percentage of bone-to-implant contact (BIC%) were analysed for the SLA-Sr and SLA implants. RESULTS: Multiple nanostructures were found on the Sr-incorporated titanium surface, and appropriate amounts of strontium ions from the SLA-Sr surface were released into the surrounding tissue within 21 days. In vivo, SLA-Sr implants displayed much more new bone around their surfaces than the SLA implants. Significantly higher RTVs and BIC% were observed for the SLA-Sr implants than for the SLA implants in both osteoporotic (p < 0.01) and healthy animals (p < 0.01) at 3 and 6 weeks. The SLA-Sr implants exhibited higher BA% in cortical bone (p < 0.01) and in cancellous bone (p < 0.05) than the SLA implants in osteoporotic rabbits at 3 weeks. CONCLUSIONS: It is suggested that Sr-incorporated surfaces treated through hydrothermal reactions have positive effects on promoting early osseointegration in both osteoporotic and non-osteoporotic rabbits.

Identification of molecular alterations in leukocytes from gene expression profiles of peripheral whole blood of Alzheimer's disease.

Blood-based test has been considered as a promising way to diagnose and study Alzheimer's disease (AD). However, the changed proportions of the leukocytes under disease states could confound the aberrant expression signals observed in mixed-cell blood samples. We have previously proposed a method, Ref-REO, to detect the leukocyte specific expression alterations from mixed-cell blood samples. In this study, by applying Ref-REO, we detect 42 and 45 differentially expressed genes (DEGs) between AD and normal peripheral whole blood (PWB) samples in two datasets, respectively. These DEGs are mainly associated with AD-associated functions such as Wnt signaling pathways and mitochondrion dysfunctions. They are also reproducible in AD brain tissue, and tend to interact with the reported AD-associated biomarkers and overlap with targets of AD-associated PWB miRNAs. Moreover, they are closely associated with aging and have severer expression alterations in the younger adults with AD. Finally, diagnostic signatures are constructed from these leukocyte specific alterations, whose area under the curve (AUC) for predicting AD is higher than 0.73 in the two AD PWB datasets. In conclusion, gene expression alterations in leukocytes could be extracted from AD PWB samples, which are closely associated with AD progression, and used as a diagnostic signature of AD.

[Application of modified lateral window for maxillary sinus floor augmentation].

Objective: To evaluate the clinical efficacy of modified lateral window for maxillary sinus floor augmentation (MSFA). Methods: Fifty-five patients who visited the Stomatology Hospital Affiliated to Zhejiang University School of Medicine between June 2012 and October 2014 were enrolled in the study. Patients underwent MSFA with Bio-Oss grafts based on modified access window. During the operation the vertical height of the bony window was reduced from 6-8 mm of conventional oval window to 4-5 mm of slot-shaped window. The sinus membrane was detached completely via the lateral access and large particle Bio-Oss graft was placed in the sub-mucosal space. The implant survival, graft height, graft volume and resorption rates were measured. Intra-op and post-op complications were recorded. Results: There were 86 implants inserted. The 2-4 year cumulative survival rates were 97.67% by implant-based analysis and 96.36% by patient-based analysis. The residual bone height was (4.7±2.6) mm and bone width was (8.4±2.7) mm. The bone height of implantation site immediately after operation was (16.1±2.5) mm and it was (16.2±2.2) mm at restoration. The bone heights at 1 and 2 years after operation were (14.9±2.5) mm and (13.6±2.6) mm, respectively. The graft height was (10.6±2.8) mm and the graft volume was (1569±745) mm3 immediately after operation. The resorption rate of graft height 6 months after operation was 3.79% and that of graft volume was 7.87%. The 1-year accumulative resorption rate of graft height was 6.63% and that of graft volume was 10.89%. The 2-year accumulative resorption rate of graft height was 7.58% and that of graft volume was 15.26%. Small membrane perforation during MSFA was observed in 5 cases and all were successfully repaired by a collagen Bio-Gide membrane. Conclusion: The modified lateral technique obtains high implant survival rate, excellent graft stability and low complication rate at 2-4 year clinical follow-up, indicating that it is a safe, predictable and minimally invasive surgical method for severe atrophic maxillary posterior dentition.