Robotic-assisted total knee arthroplasty improves implant position and early functional recovery for the knee with severe varus/valgus deformity.

PURPOSE: Robotic-assisted total knee arthroplasty (r-TKA) facilitates precise bone resection and lower limb alignment, yet accuracy and functional recovery for severe varus/valgus deformity is not well-documented. The aim of study was to investigate whether r-TKA improves implant alignment in the coronal and sagittal view and early functional recovery compared to conventional TKA(c-TKA). METHODS: This comparative study included 86 patients with symptomatic knee arthritis who underwent primary TKA at our institution between 1st May and 31th November 2021. Radiological parameters evaluated included hip-knee-ankle angle (HKAA), femoral varus-valgus angle (FVVA), tibial varus-valgus angle (TVVA), posterior tibial slope angle (PTSA), femoral sagittal angle (FSA), posterior condylar offset ratio, and Insall-Salvati index. Operative time, stay length, and complications were reviewed from patient records. The hospital for special surgery (HSS), Visual Analogue Scale (VAS) and knee joint motion range were evaluated at the six-month follow-up. RESULTS: The c-TKA and r-TKA groups had no significant differences in HKAA (179.73 ± 3.76°, range: 172.10-188.90° vs. 180.53 ± 2.91°, range: 173.30-188.32°, p = 0.277), FVVA (96.13 ± 2.61°, range: 90.27-101.52° vs. 96.38 ± 2.23°, range: 90.98-100.95°, p = 0.636), and TVVA (88.74 ± 2.03°, range: 83.75-92.74° vs. 89.43 ± 1.83°, range: 85.32-94.15°, p = 1.000). Outlier of mechanical alignment incidence (> 3°) was significantly lower in r-TKA compared with c-TKA, 17.50% (7/40) vs. 41.30% (19/46), (p = 0.017). PTSA of r-TKA remained significantly lower than c-TKA (p = 0.009) in mild-deformity patients. For severe varus/valgus deformity, r-TKA had a significantly lesser HKAA-outlier incidence (p = 0.025), PTSA-outlier incidence (p = 0.019), and lower PTSA (p < 0.001) compared with c-TKA. The r-TKA functional outcome was better than c-TKA regarding HSS (93.12 ± 1.97, range: 90-95, 95%CI:92.11-94.13 vs. 91.33 ± 2.50, range: 85-95, 95%CI:90.20-92.69, p = 0.036), and VAS (0.24 ± 0.44, range:0-1 vs. 0.72 ± 0.75, range:0-2, p = 0.026), knee joint flexion (118.53° ± 8.06, range: 105-130°, 95%CI:114.39-122.67° vs. 112.22 ± 8.09°, range: 100-130°, 95%CI:108.20-116.24° ,p = 0.027) for severe varus/valgus deformity. CONCLUSION: r-TKA improved lower-limb coronal alignment, sagittal implant position, and early functional recovery for patients with severe varus/valgus deformity of the knee. r-TKA did not confer substantial advantages over c-TKA in both radiological and clinical outcomes for the mild varus/valgus deformity.

Insufficient stem antetorsion and lower cup abduction is a combined risk factor for posterior hip dislocation in patients undergoing THA for femoral neck fractures: a retrospective analysis.

BACKGROUND: The role of acetabular and femoral component positions with respect to the risk of post-operative instability and dislocation remains debated. In this study, we aimed to identify potential risk factors for early dislocation following primary total hip arthroplasty (THA) for displaced intracapsular femoral neck fractures (FNF) using radiological measurements. METHODS: We retrospectively analyzed data for patients who underwent cementless primary THA for FNF using a posterolateral approach between January 2018 and December 2021. Follow-up duration, age, sex, affected side, and mean time from THA to dislocation were recorded. Leg-length inequality, abductor lever arm, vertical and horizontal femoral offsets, vertical and horizontal hip centers of rotation, abduction, anteversion of the acetabulum and femoral prosthesis, and combined anteversion were measured. RESULTS: The study sample included 17 men and 34 women, with 21 and 30 patients undergoing left- and right-hip operations, respectively. The mean patient age was 70.18 ± 7.64 years, and the mean follow-up duration was 27.73 ± 13.52 months. The mean time between THA and dislocation was 1.58 ± 0.79 months. Seven patients (13.73%) sustained posterior dislocation of the hip. The abduction angle (36.05 ± 6.82° vs. 45.68 ± 8.78°) (p = 0.008) and anteversion of the femoral prosthesis (8.26 ± 4.47° vs. 19.47 ± 9.01°) (p = 0.002) were significantly lower in the dislocation group than in the control group. There were no significant differences in other parameters. CONCLUSIONS: Insufficient stem antetorsion combined with lower abduction angle of the acetabular component were associated with a high risk of dislocation, especially in patients with deep flexion or internal rotation of the flexed hip joint and knees, or in patients with a stiff spine or anterior pelvic tilt, impingement may then occur in the neck of the prosthesis and cup component, ultimately resulting in posterior dislocation. These findings could remind surgeons to avoid simultaneous occurrence of both in THA surgery. These results provide new insight into risk factors for hip dislocation in patients undergoing primary THA for FNF and may aid in reducing the risk of instability and dislocation. LEVEL OF EVIDENCE: Prospective comparative study Level II.

The small screw-apex distance is potentially associated with femoral head osteonecrosis in adults with femoral neck fractures treated by closed reduction and percutaneous 3 parallel cannulated screws.

OBJECTIVE: Femoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH. PATIENTS AND METHODS: A total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors' institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated. RESULTS: The sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively). CONCLUSIONS: The short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region.

Small non-coding RNAome changes during human chondrocyte senescence as potential epigenetic targets in age-related osteoarthritis.

Chondrocyte senescence is a decisive component of age-related osteoarthritis, however, the function of small noncoding RNAs (sncRNAs) in chondrocyte senescence remains underexplored. Human hip joint cartilage chondrocytes were cultivated up to passage 4 to induce senescence. RNA samples were extracted and then analyzed using small RNA sequencing and qPCR. ß-galactosidase staining was used to detect the effect of sncRNA on chondrocyte aging. Results of small RNA sequencing showed that 279 miRNAs, 136 snoRNAs, 30 snRNAs, 102 piRNAs, and 5 rasiRNAs were differentially expressed in senescent chondrocytes. The differential expression of 150 sncRNAs was further validated by qPCR. Transfection of sncRNAs and ß-galactosidase staining were also performed to further revealed that hsa-miR-135b-5p, SNORA80B-201, and RNU5E-1-201 have the function to restrain chondrocyte senescence, while has-piR-019102 has the function to promote chondrocyte senescence. Our data suggest that sncRNAs have therapeutic potential as novel epigenetic targets in age-related osteoarthritis.

Single-cell RNA sequencing profiles reveal cell type-specific transcriptional regulation networks conditioning fungal invasion in maize roots.

Stalk rot caused by Fusarium verticillioides (Fv) is one of the most destructive diseases in maize production. The defence response of root system to Fv invasion is important for plant growth and development. Dissection of root cell type-specific response to Fv infection and its underlying transcription regulatory networks will aid in understanding the defence mechanism of maize roots to Fv invasion. Here, we reported the transcriptomes of 29 217 single cells derived from root tips of two maize inbred lines inoculated with Fv and mock condition, and identified seven major cell types with 21 transcriptionally distinct cell clusters. Through the weighted gene co-expression network analysis, we identified 12 Fv-responsive regulatory modules from 4049 differentially expressed genes (DEGs) that were activated or repressed by Fv infection in these seven cell types. Using a machining-learning approach, we constructed six cell type-specific immune regulatory networks by integrating Fv-induced DEGs from the cell type-specific transcriptomes, 16 known maize disease-resistant genes, five experimentally validated genes (ZmWOX5b, ZmPIN1a, ZmPAL6, ZmCCoAOMT2, and ZmCOMT), and 42 QTL or QTN predicted genes that are associated with Fv resistance. Taken together, this study provides not only a global view of maize cell fate determination during root development but also insights into the immune regulatory networks in major cell types of maize root tips at single-cell resolution, thus laying the foundation for dissecting molecular mechanisms underlying disease resistance in maize.

Adaptations to 4 weeks of high-intensity interval training in healthy adults with different training backgrounds.

PURPOSE: This study investigated the physical fitness and oxygen uptake kinetics ([Formula: see text]) along with the exercise-onset O2 delivery (heart rate kinetics, τHR; changes in normalized deoxyhemoglobin/[Formula: see text] ratio, Δ[HHb]/[Formula: see text]) adaptations of individuals with different physical activity (PA) backgrounds responding to 4 weeks of high-intensity interval training (HIIT), and the possible effects of skeletal muscle mass (SMM) on training-induced adaptations. METHODS: Twenty subjects (10 high-PA level, HIIT-H; 10 moderate-PA level, HIIT-M) engaged in 4 weeks of treadmill HIIT. Ramp-incremental (RI) test and step-transitions to moderate-intensity exercise were performed. Cardiorespiratory fitness, body composition, muscle oxygenation status, VO2 and HR kinetics were assessed at baseline and post-training. RESULTS: HIIT improved fitness status for HIIT-H ([Formula: see text], + 0.26 ± 0.07 L/min; SMM, + 0.66 ± 0.70 kg; body fat, - 1.52 ± 1.93 kg; [Formula: see text], - 7.11 ± 1.05 s, p < 0.05) and HIIT-M ([Formula: see text], 0.24 ± 0.07 L/min, SMM, + 0.58 ± 0.61 kg; body fat, - 1.64 ± 1.37 kg; [Formula: see text], - 5.48 ± 1.05 s, p < 0.05) except for visceral fat area (p = 0.293) without between-group differences (p > 0.05). Oxygenated and deoxygenated hemoglobin amplitude during the RI test increased for both groups (p < 0.05) except for total hemoglobin (p = 0.179). The Δ[HHb]/[Formula: see text] overshoot was attenuated for both groups (p < 0.05) but only eliminated in HIIT-H (1.05 ± 0.14 to 0.92 ± 0.11), and no change was observed in τHR (p = 0.144). Linear mixed-effect models presented positive effects of SMM on absolute [Formula: see text] (p < 0.001) and ΔHHb (p = 0.034). CONCLUSION: Four weeks of HIIT promoted positive adaptations in physical fitness and [Formula: see text] kinetics, with the peripheral adaptations attributing to the observed improvements. The training effects are similar between groups suggesting that HIIT is effective for reaching higher physical fitness levels.

Aerobic capacity and [Formula: see text] kinetics adaptive responses to short-term high-intensity interval training and detraining in untrained females.

PURPOSE: This study investigated the physical fitness and oxygen uptake kinetics (τ[Formula: see text]) along with the O2 delivery and utilization (heart rate kinetics, τHR; deoxyhemoglobin/[Formula: see text] ratio, ∆[HHb]/[Formula: see text]) adaptations of untrained female participants responding to 4 weeks of high-intensity interval training (HIIT) and 2 weeks of detraining. METHODS: Participants were randomly assigned to HIIT (n = 11, 4 × 4 protocol) or nonexercising control (n = 9) groups. Exercising group engaged 4 weeks of treadmill HIIT followed by 2 weeks of detraining while maintaining daily activity level. Ramp-incremental (RI) tests and step-transitions to moderate-intensity exercise were performed. Aerobic capacity and performance (maximal oxygen uptake, [Formula: see text]; gas-exchange threshold, GET; power output, PO), body composition (skeletal muscle mass, SMM; body fat percentage, BF%), muscle oxygenation status (∆[HHb]), [Formula: see text], and HR kinetics were assessed. RESULTS: HIIT elicited improvements in aerobic capacity ([Formula: see text], + 0.17 ± 0.04 L/min; GET, + 0.18 ± 0.05 L/min, P < 0.01; PO-[Formula: see text], ± 23.36 ± 8.37 W; PO-GET, + 17.18 ± 3.07 W, P < 0.05), body composition (SMM, + 0.92 ± 0.17 kg; BF%, - 3.08% ± 0.58%, P < 0.001), and speed up the τ[Formula: see text] (- 8.04 ± 1.57 s, P < 0.001) significantly, extending to better ∆[HHb]/[Formula: see text] ratio (1.18 ± 0.08 to 1.05 ± 0.14). After a period of detraining, the adaptation in body composition and aerobic capacity, as well as the accelerated τ[Formula: see text] were maintained in the HIIT group, but the PO-[Formula: see text] and PO-GET declined below the post-training level (P < 0.05), whereas no changes were reported in controls (P > 0.05). Four weeks of HIIT induced widespread physiological adaptations in females, and the majority of improvements were preserved after 2 weeks of detraining except for power output corresponding to [Formula: see text] and GET.

Zinc Oxide Quantum Dots May Provide a Novel Potential Treatment for Antibiotic-Resistant Streptococcus agalactiae in Lama glama.

Streptococcus agalactiae is a significant pathogen that can affect both human beings and animals. The extensive current use of antibiotics has resulted in antibiotic resistance. In our previous research, we found that zinc oxide quantum dots (ZnO QDs) had inhibitory effects on antibiotic-resistant microorganisms. In this study, a strain of Streptococcus agalactiaeWJYT1 with a broad antibiotic-resistant spectrum was isolated and identified from Lama glama at Sichuan Agricultural University Teaching Animal Hospital. The genome for the resistance and virulence genes was analyzed. Additionally, the antibacterial effects and anti-virulence mechanism of ZnO QDs for S. agalactiaeWJYT1 were investigated. The results showed that the genome of S. agalactiaeWJYT1 is 1,943,955 bp, containing 22 resistance genes and 95 virulence genes. ZnO QDs have a good antibacterial effect against S. agalactiaeWJYT1 by reducing bacterial growth and decreasing the expression of virulence genes, including bibA, hylB, sip, and cip, which provides a novel potential treatment for S. agalactiae.

Pollution characteristics and source analysis of heavy metals in surface sediments of Luoyuan Bay, Fujian.

The concentrations of eight heavy metals, V, Cr, Co, Ni, Cu, Zn, Cd, and Pb, were analyzed to explore the environmental pollution characteristics, ecological risk levels, and sources of heavy metals in the surface sediments of Luoyuan Bay in Fujian Province. The results indicated that the mean concentrations of V, Cr, Co, Ni, Cu, Zn, Cd, and Pb were 110.44, 97.76, 17.35, 41.99, 36.78, 137.26, 0.09, and 35.81 mg⋅kg-1, respectively. The mean concentrations of Cr, Cu, and Zn exceeded the first category of the marine sediment quality standards, indicating a moderate regional comprehensive potential ecological hazard level. Due to variable hydrodynamic conditions, high concentrations of heavy metals were observed in the north and low concentrations were observed in the south, with high values generally recorded near steel plants and shipyard docks. Correlation and principal component analyses revealed that the V, Al, Co, Ni, and Pb originated from the weathering and erosion of rocks, and industrial wastewater discharge. Contrastingly, Cu, Zn, Cr, and Cd were mainly associated with the transportation and repair of ships, and marine aquaculture activities.

Joint Hidden Markov Model for Longitudinal and Time-to-Event Data with Latent Variables.

This study develops a new joint modeling approach to simultaneously analyze longitudinal and time-to-event data with latent variables. The proposed model consists of three components. The first component is a hidden Markov model for investigating a longitudinal observation process and its underlying transition process as well as their potential risk factors and dynamic heterogeneity. The second component is a factor analysis model for characterizing latent risk factors through multiple observed variables. The third component is a proportional hazards model for examining the effects of observed and latent risk factors on the hazards of interest. A shared random effect is introduced to allow the longitudinal and time-to-event outcomes to be correlated. A Bayesian approach coupled with efficient Markov chain Monte Carlo methods is developed to conduct statistical inference. The performance of the proposed method is evaluated through simulation studies. An application of the proposed model to a general health survey study concerning cognitive impairment and mortality for Chinese elders is presented.

Transition to renewable energy and environmental technologies: The role of economic policy uncertainty in top five polluted economies.

The United Nations' "Sustainable Development Goals" (SDGs) express attention to climate action. Even though a considerable number of papers have targeted this issue, the literature on the top five, "China, India, Japan, Russia, and the United States" economies is uncommon. Therefore, this paper is targeted to examine the influence of renewable energy (RE), environmental technologies (ETs), and economic policy uncertainty (EPU) on carbon emissions. By using the most recent data available from 1992 to 2020, results are estimated with robust econometric techniques, i. e. "cross-sectionally augmented autoregressive distributed lag (CS-ARDL) and augmented mean group (AMG)". Findings reflect the harmful role of EPU. However, RE and ETs have a supportive role in the transition towards a sustainable environment. The findings are also strong in terms of policy implications for the top five polluters.

Exposure to 1-Butanol Exemplifies the Response of the Thermoacidophilic Archaeon Sulfolobus acidocaldarius to Solvent Stress.

Sulfolobus acidocaldarius is a thermoacidophilic crenarchaeon with optimal growth at 80°C and pH 2 to 3. Due to its unique physiological properties, allowing life at environmental extremes, and the recent availability of genetic tools, this extremophile has received increasing interest for biotechnological applications. In order to elucidate the potential of tolerating process-related stress conditions, we investigated the response of S. acidocaldarius toward the industrially relevant organic solvent 1-butanol. In response to butanol exposure, biofilm formation of S. acidocaldarius was enhanced and occurred at up to 1.5% (vol/vol) 1-butanol, while planktonic growth was observed at up to 1% (vol/vol) 1-butanol. Confocal laser-scanning microscopy revealed that biofilm architecture changed with the formation of denser and higher tower-like structures. Concomitantly, changes in the extracellular polymeric substances with enhanced carbohydrate and protein content were determined in 1-butanol-exposed biofilms. Using scanning electron microscopy, three different cell morphotypes were observed in response to 1-butanol. Transcriptome and proteome analyses were performed comparing the response of planktonic and biofilm cells in the absence and presence of 1-butanol. In response to 1% (vol/vol) 1-butanol, transcript levels of genes encoding motility and cell envelope structures, as well as membrane proteins, were reduced. Cell division and/or vesicle formation were upregulated. Furthermore, changes in immune and defense systems, as well as metabolism and general stress responses, were observed. Our findings show that the extreme lifestyle of S.acidocaldarius coincided with a high tolerance to organic solvents. This study provides what may be the first insights into biofilm formation and membrane/cell stress caused by organic solvents in S. acidocaldariusIMPORTANCEArchaea are unique in terms of metabolic and cellular processes, as well as the adaptation to extreme environments. In the past few years, the development of genetic systems and biochemical, genetic, and polyomics studies has provided deep insights into the physiology of some archaeal model organisms. In this study, we used S. acidocaldarius, which is adapted to the two extremes of low pH and high temperature, to study its tolerance and robustness as well as its global cellular response toward organic solvents, as exemplified by 1-butanol. We were able to identify biofilm formation as a primary cellular response to 1-butanol. Furthermore, the triggered cell/membrane stress led to significant changes in culture heterogeneity accompanied by changes in central cellular processes, such as cell division and cellular defense systems, thus suggesting a global response for the protection at the population level.

The treatment of posterolateral tibial plateau fracture with a newly designed anatomical plate via the trans-supra-fibular head approach: preliminary outcomes.

BACKGROUND: There are no ideal plates or approaches for anatomical restoration and rigid fixation of posterolateral tibial plateau fractures. This study aimed to evaluate the short-term preliminary outcomes of our novel anatomical plate placed via the trans-supra-fibular approach to treat posterolateral tibial plateau fractures. METHODS: From May 2016 to May 2018, 23 consecutive patients with posterolateral tibial quadrant fractures underwent open reduction with internal fixation via the trans-supra-fibular-head approach with our newly developed plate. The tibial plateau-tibial shaft angle (TPTSA), lateral posterior tibial slope angle (LPSTA), step-off, and condylar widening were measured on radiological images pre-operatively, 3 days post-operatively, 3 months post-operatively, and at the final follow-up examination. The radiological Rasmussen score was calculated, and the Hospital for Special Surgery (HSS) knee score was assessed to evaluate the functional outcomes. RESULTS: The LTPSA, TPTSA, step-off, and condylar widening at 3 days post-operatively, 3 months post-operatively, and at the final follow-up were significantly different (p = 0.001) compared with those pre-operatively, as was the radiological Rasmussen score (p = 0.001). The HSS score at the final follow-up was 89.10 ± 5.94 (range, 78-98), which was significantly higher than that at the 3-month follow-up 84.36 ± 6.76 (range, 74-96); p = 0.001). CONCLUSIONS: Our newly designed anatomical plate placed via the trans-supra-fibular approach can effectively treat posterolateral tibial plateau fractures. We noted minor trauma, stable fixation, and satisfactory clinical results.

Does environmental regulation induce improved financial development for green technological innovation in China?

The effect of environmental regulations on the nexus between financial development and biased technological innovation is a prerequisite for optimizing systems of environmental and financial policies to gain sustainable development goals (SDGs) in emerging markets. Drawing on China's city-level data from 2003 to 2018, we established econometric models and obtained the following empirical results. Financial development (FD) can promote energy- and environmental-biased technological progress, but, owing to the inverted U-shaped relationship, economic development, and resource endowment, the impact that FD has on biased technological progress is heterogeneous; unreasonable FD will also hinder green technological progress. Threshold model shows that with the improvement of environmental regulation, the impact of energy- and environmental-biased technological progress is also increasing. The development of green finance under SDGs is an important driving force in green technological progress. Finally, we offer suggestions to optimize environmental and financial policymaking and implementation from a government intervention perspective.

Glycine metabolomic changes induced by anticancer agents in A549 cells.

Glycine plays a key role in rapidly proliferating cancer cells such as A549 cells. Targeting glycine metabolism is considered as a potential means for cancer treatment. However, the drug-induced alterations in glycine metabolism have not yet been investigated. Herein, a total of 34 glycine metabolites were examined in A549 cells with or without anticancer drug treatment. This work showed all tested anticancer agents could alter glycine metabolism in A549 cells including inhibition of pyruvate metabolism and down-regulation of betaine aldehyde and 5'-phosphoribosylglycinamide. Principal component analysis and orthogonal partial least-squares discrimination analysis exhibited the difference between control and each drug-treated group. In general, cisplatin, camptothecin, and SAHA could induce the significant down-regulation of more metabolites, compared with afatinib, gefitinib, and targretin. Both glycine, serine and threonine metabolism, and purine metabolism were significantly disturbed by the treatment with afatinib, gefitinib, and targretin. However, the treatment using cisplatin, camptothecin, and SAHA was considered to be highly responsible for the perturbation of glycine, serine and threonine metabolism, and cysteine and methionine metabolism. Finally, multivariate analysis for control and all drug-treated groups revealed 11 altered metabolites with a significant difference. It implies anti-cancer agents with different mechanisms of action might induce different comprehensive changes of glycine metabolomics. The current study provides fundamental insights into the acquisition of the role of anti-cancer agents in glycine metabolism while suppressing cancer cell proliferation, and may aid the development of cancer treatment targeting glycine metabolism.

Two-part hidden Markov models for semicontinuous longitudinal data with nonignorable missing covariates.

This study develops a two-part hidden Markov model (HMM) for analyzing semicontinuous longitudinal data in the presence of missing covariates. The proposed model manages a semicontinuous variable by splitting it into two random variables: a binary indicator for determining the occurrence of excess zeros at all occasions and a continuous random variable for examining its actual level. For the continuous longitudinal response, an HMM is proposed to describe the relationship between the observation and unobservable finite-state transition processes. The HMM consists of two major components. The first component is a transition model for investigating how potential covariates influence the probabilities of transitioning from one hidden state to another. The second component is a conditional regression model for examining the state-specific effects of covariates on the response. A shared random effect is introduced to each part of the model to accommodate possible unobservable heterogeneity among observation processes and the nonignorability of missing covariates. A Bayesian adaptive least absolute shrinkage and selection operator (lasso) procedure is developed to conduct simultaneous variable selection and estimation. The proposed methodology is applied to a study on the Alzheimer's Disease Neuroimaging Initiative dataset. New insights into the pathology of Alzheimer's disease and its potential risk factors are obtained.

Modified osteotomy of posterolateral overhanging part of the trochanter via posterior approach for hip arthroplasty: an anatomical study.

BACKGROUD: The osteotomy of the posterolateral overhanging part (PLOP) of the greater trochanter via posterior approach has been used for the hip arthroplasty for decades with good results. However, the osteotomy method remains undefined and the precise adjacent structures around PLOP have not been reported. The purpose of this study was to present a modified PLOP osteotomy approach and perform a detailed study of the topographic and surgical anatomy of the PLOP. METHODS: The peri-PLOP soft tissue and the bony parameters were measured using 10 cadavers with 20 hips and 20 skeletal hip specimens, respectively. RESULTS: A 1.8-cm vertical osteotomy did not jeopardize the femoral neck, and a 1.8-cm wide bone block did not damage the insertions of the short external rotators. The average distances between the most distal branch of the superior gluteal nerve/artery and the 1.8-cm point of the greater trochanter were 5.70 ± 0.66 cm and 6.33 ± 0.56 cm, respectively. CONCLUSION: For osteotomy of the PLOP, we suggested that the width of the upper side from the lateral to medial greater trochanter should be 1.8 cm, depth of vertical osteotomy should be 1.8 cm, and length of the posterior edge should be 4 cm. Obturator externus tendon should be kept within the bone block of osteotomy. The proximal extension of the gluteus medius muscle split should be limited to 5.5 cm at the 1.8 cm-point of the greater trochanter. LEVEL OF EVIDENCE: Prospective comparative study Level II.

Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy.

Recently, tumor neoantigens have been attractive for development of personal therapeutic vaccines. However, how to instantly deliver multiple neoantigens for efficient anti-tumor immunity is still challenging. Here, we established a SpyCatcher-modified ferritin nanoparticle platform, which permits convenient and stable covalent conjugation with tumor specific antigens containing SpyTag in a click-link manner. These ferritin nanoparticles are rapidly drained to lymph nodes and target dendritic cells, especially CD8α+ population, upon subcutaneous immunization. Ferritin nanoparticles carrying HPV16 oncogene E7 peptide antigen or MC38 tumor derived mutant neoantigens elicit about 2-3 folds enhanced antigen-specific cytotoxic T lymphocyte (CTL) response than soluble peptide antigens and significantly suppress the growth of E7-related or MC38 tumors. The anti-tumor effect was further enhanced in combination with PD-1 checkpoint blockade. Together, our study provides a ferritin nanoparticle-based, SpyTag/SpyCatcher-enabled click vaccine platform, especially for personalized tumor immunotherapy.

Anatomic locking plates for complex proximal humeral fractures: anatomic neck fractures versus surgical neck fractures.

BACKGROUND: Continued debate exists on the management of displaced 3- or 4-part proximal humeral fractures. Only a few studies have compared the efficacy of proximal humeral locking plates (PHLPs) for treating anatomic neck fractures (ANFs) and surgical neck fractures (SNFs). METHODS: The medical data of 31 consecutive patients with displaced 4-part proximal humeral fractures treated with PHLPs between May 2013 and April 2015 were reviewed retrospectively. We divided the patients into the ANF and SNF groups and assessed the neck-shaft angle (NSA), sum of the screw tip-articular surface distance, and other parameters postoperatively at 3 days and at 12 months using shoulder radiographs. The Constant-Murley scores were assessed at 3 days, 12 months, and last follow-up. RESULTS: The ANF group had a significantly lower mean age and significantly greater mean operative duration, estimated blood loss, and rate of bone grafting. Full or partial osteonecrosis of the humeral head developed in 7 patients and 1 patient in the ANF and SNF groups, respectively. Screw cutout and/or pullout complications occurred in 8 cases in the ANF group but not in the SNF group. In the ANF group, the values for NSA and the sum of the screw tip-articular surface distance changed significantly from 3 days to 12 months postoperatively. There were no significant correlations among the tested parameters. CONCLUSION: ANFs resulted in more complications at a younger age than SNFs. ANF treatment using PHLPs is more prone to a decreased NSA and humeral head osteonecrosis and has poorer clinical outcomes than SNF treatment using PHLPs.

Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free ß-thalassemia induced pluripotent stem cells.

ß-Thalassemia (ß-Thal) is a group of life-threatening blood disorders caused by either point mutations or deletions of nucleotides in ß-globin gene (HBB). It is estimated that 4.5% of the population in the world carry ß-Thal mutants (1), posing a persistent threat to public health. The generation of patient-specific induced pluripotent stem cells (iPSCs) and subsequent correction of the disease-causing mutations offer an ideal therapeutic solution to this problem. However, homologous recombination-based gene correction in human iPSCs remains largely inefficient. Here, we describe a robust process combining efficient generation of integration-free ß-Thal iPSCs from the cells of patients and transcription activator-like effector nuclease (TALEN)-based universal correction of HBB mutations in situ. We generated integration-free and gene-corrected iPSC lines from two patients carrying different types of homozygous mutations and showed that these iPSCs are pluripotent and have normal karyotype. We showed that the correction process did not generate TALEN-induced off targeting mutations by sequencing. More importantly, the gene-corrected ß-Thal iPS cell lines from each patient can be induced to differentiate into hematopoietic progenitor cells and then further to erythroblasts expressing normal ß-globin. Our studies provide an efficient and universal strategy to correct different types of ß-globin mutations in ß-Thal iPSCs for disease modeling and applications.