A data harmonization pipeline to leverage external controls and boost power in GWAS.

The use of external controls in genome-wide association study (GWAS) can significantly increase the size and diversity of the control sample, enabling high-resolution ancestry matching and enhancing the power to detect association signals. However, the aggregation of controls from multiple sources is challenging due to batch effects, difficulty in identifying genotyping errors and the use of different genotyping platforms. These obstacles have impeded the use of external controls in GWAS and can lead to spurious results if not carefully addressed. We propose a unified data harmonization pipeline that includes an iterative approach to quality control and imputation, implemented before and after merging cohorts and arrays. We apply this harmonization pipeline to aggregate 27 517 European control samples from 16 collections within dbGaP. We leverage these harmonized controls to conduct a GWAS of Crohn's disease. We demonstrate a boost in power over using the cohort samples alone, and that our procedure results in summary statistics free of any significant batch effects. This harmonization pipeline for aggregating genotype data from multiple sources can also serve other applications where individual level genotypes, rather than summary statistics, are required.

Advances of Layered Double Hydroxide-Based Materials for Tumor Imaging and Therapy.

Layered double hydroxides (LDH) are a class of functional anionic clays that typically consist of orthorhombic arrays of metal hydroxides with anions sandwiched between the layers. Due to their unique properties, including high chemical stability, good biocompatibility, controlled drug loading, and enhanced drug bioavailability, LDHs have many potential applications in the medical field. Especially in the fields of bioimaging and tumor therapy. This paper reviews the research progress of LDHs and their nanocomposites in the field of tumor imaging and therapy. First, the structure and advantages of LDH are discussed. Then, several commonly used methods for the preparation of LDH are presented, including co-precipitation, hydrothermal and ion exchange methods. Subsequently, recent advances in layered hydroxides and their nanocomposites for cancer imaging and therapy are highlighted. Finally, based on current research, we summaries the prospects and challenges of layered hydroxides and nanocomposites for cancer diagnosis and therapy.

Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination.

B-cell depletion induced by anti-cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, but effects on CD8 T-cell responses are unknown. Here, we investigated humoral and CD8 T-cell responses following two vaccinations in patients with lymphoma undergoing anti-CD20-mAb therapy as single agent or in combination with chemotherapy or other anti-neoplastic agents during the last 9 months prior to inclusion, and in healthy age-matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor-binding domain of the SARS-CoV-2 Spike protein 3-6 weeks after the second dose of vaccination. Peripheral blood CD8 T-cell responses against prevalent human leucocyte antigen (HLA) class I SARS-CoV-2 epitopes were determined by peptide-HLA multimer analysis. Strong CD8 T-cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS-CoV-2-vaccinated, anti-CD20-treated patients with lymphoma, their CD8 T-cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B-cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID-19) vaccines, and development of vaccines aimed at eliciting T-cell responses to non-Spike epitopes might provide improved protection.

Pharmacological Therapies for Osteoporosis: A Bayesian Network Meta-Analysis.

BACKGROUND Numerous randomized controlled trials (RCTs) have evaluated pharmacological therapies for osteoporosis. The aim of this Bayesian network meta-analysis was to compare the efficacy and safety of pharmacological therapies for osteoporosis patients. MATERIAL AND METHODS The electronic databases of PubMed, Embase, and Cochrane Library were systematically searched for eligible RCTs from their inception up to January 2021. The primary endpoints were all fractures, vertebral fractures, and non-vertebral fractures, while the secondary endpoints were fractures at hip or peripheral locations, bone mineral density (BMD) at various sites, and potential adverse events. RESULTS We included 79 RCTs reporting a total of 108 797 individuals in the final quantitative analysis. The results of network analysis indicated that romosozumab (92.1%) was the most effective in reducing the risk for all fractures, with the best therapeutic effects on vertebral fracture (97.2%) and non-vertebral fracture (88.0%). Romosozumab (92.5%) provided better therapeutic effects for the reduction of hip fracture. The best treatment agents for improving whole-body BMD (100.0%), spine BMD (95.7%), hip BMD (92.4%), femoral neck BMD (86.7%), and trochanter BMD (95.5%) were alendronate, strontium ranelate, ibandronate, risedronate, and ibandronate, respectively. Finally, the use of bazedoxifene was associated with the highest incidence of any upper-gastrointestinal event, nasopharyngitis, and back pain, while risedronate was associated with higher incidence of abdominal pain and dyspepsia. CONCLUSIONS This study found that romosozumab yielded the best effects for preventing fracture risk, while abaloparatide was the most effective in reducing the risk of vertebral fracture and non-vertebral fracture.

Heritability of tea drinking and its relationship with cigarette smoking in the Chinese male adult twins.

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.

Identification of MHC Class Ib Ligands for Stimulatory and Inhibitory Ly49 Receptors and Induction of Potent NK Cell Alloresponses in Rats.

Early studies indicate that rats may have a repertoire of MHC class Ib-reactive Ly49 stimulatory receptors capable of mounting memory-like NK cell alloresponses. In this article, we provide molecular and functional evidence for this assumption. Pairs of Ly49 receptors with sequence similarities in the lectin-like domains, but with opposing signaling functions, showed specificity for ligands with class Ia-like structural features encoded from the first telomeric MHC class Ib gene cluster, RT1-CE, which is syntenic with the H2-D/H2-L/H2-Q cluster in mice. The activating Ly49s4 receptor and its inhibitory counterparts, Ly49i4 and Ly49i3, reacted with all allelic variants of RT1-U, whereas Ly49s5 and Ly49i5 were specific for RT1-Eu NK cell cytolytic responses were predictably activated and inhibited, and potent in vivo NK alloresponses were induced by repeated MHC class Ib alloimmunizations. Additional Ly49-class Ib interactions, including RT1-Cl with the Ly49s4/Ly49i4/Ly49i3 group of receptors, were characterized using overexpressed receptor/ligand pairs, in vitro functional assays, and limited mutational analyses. Obvious, as well as subtle, Ly49-class Ib interactions led to ligand-induced receptor calibration and NK subset expansions in vivo. Together, these studies suggest that in vivo NK alloresponses are controlled by pleomorphic Ly49-class Ib interactions, some of which may not be easily detectable in vitro.

[Post-marketing intensive safety monitoring of Injection of Xuesaitong (lyophilized) in 30097 cases].

To investigate the safety of Injection of Xuesaitong(lyophilized) in clinical "real world" application, including the types, incidence, as well as the severity and treatment measures of adverse reactions/adverse events. This will serve as a basis for hospitals and enterprises to develop risk control measures. A prospective, multi-center, and large-sample hospital centralized monitoring method was used to conduct post-marketing safety monitoring of Injection of Xuesaitong(lyophilized) in medical institutions nationwide. Paper case report forms were adopted to collect general information, medication and adverse reaction information of patients using Injection of Xuesaitong(lyophilized). Data analysis was performed by using SAS 9.1 software. The study included 79 hospitals with 30 097 patients. 199 cases of adverse events were found in patients administered with Injection of Xuesaitong(lyophilized), a total of 206 times. Among 199 cases, 40 of them showed adverse reactions, accounting for an overall incidence of 0.13% and 95%CI[0.09%,0.17%], which was an occasional grade. There were 38 cases of mild adverse reactions, accounting for 95.0%, 2 cases of moderate adverse reactions, accounting for 5.0%. Adverse reaction symptoms were relieved in six patients, accounting for 15.0% of the total number of adverse reactions, adverse reaction symptoms disappeared in 34 cases, with an overall percentage of 85.0%. The results of the study showed the adverse reactions in patients using Injection of Xuesaitong(lyophilized) were rare and mild, with a good prognosis. Therefore, clinical administration of Injection of Xuesaitong(lyophilized) is relatively safe.

[Analysis of Injection of Xuesaitong (lyophilized) in 30097 cases in real world].

To investigate the extensive application of Injection of Xuesaitong(lyophilized) in clinical real world study, and provide basis for clinical guidance on rational drug use and improvement of drug instructions. A prospective, multi-center, large-sample hospital centralized monitoring method was adopted to collect the general information and medication information of all patients who received Injection of Xuesaitong(lyophilized) during the study period in the respective monitoring units. Data analysis was performed using SAS 9.1 software. This study included 79 hospitals, with 30 097 patients being recruited. The patients who met the indications for stroke and hemiplegia accounted for 31.18%, those who experienced indications of chest pain and heartache accounted for 23.15%, and patients with central retinal vein occlusion indication accounted for 0.53%. The minimum single dose of Injection of Xuesaitong(lyophilized) was 20 mg, the maximum single dose was 1 000 mg, and the average single dose was(383.31±78.10) mg. 69.96% of the patients used 0.9% sodium chloride as the menstruum, 28.78% of the patients used 5% glucose as the menstruum, and 0.19% of the patients used 10% glucose as the menstruum. The minimum time for Injection of Xuesaitong(lyophilized) to dissolve is 0 min, 120 min maximally, and(14.26±13.73) min on an average basis. Patients using Injection of Xuesaitong(lyophilized) by intravenous drip accounted for 99.93%, with a slowest drip rate of 10 drops per min, fastest drip rate of 80 drops per min, and an average of(43.91±10.77) drops per min. Injection of Xuesaitong(lyophilized) was used for a minimum of 1 day and a maximum of 80 days, with an average of(8.22±5.12) days. Combined use with other injections accounted for 80.67%, 47.14% of them flushed the tube and 3.31% of them replaced infusion sets. The study found 40 cases of adverse reactions in patients with Injection of Xuesaitong(lyophilized), with an overall incidence of 0.13%(0.09% to 0.17%) for adverse reactions. In the real world application, the usage of Injection of Xuesaitong(lyophilized) basically meets the requirement of drug instructions in terms of indications, dosages, and methods of administration. However, it still needs to be improved in standardizing the selection of the menstruum, drip rate, course of treatment, and the combined usage of medicine.

In Situ Fabrication of Hierarchical MTW Zeolite via Nanoparticle Assembly by a Tailored Simple Organic Molecule.

Amphiphilic surfactants are widely used as templates to synthesize hierarchically structured zeolites due to their multiple functions; however, piloting such new dual-functional templates is limited by their time-consuming nature and high cost. Herein, a simple organic molecule, without a long hydrophobic alkyl chain, was tailored from a gemini-type, poly-quaternary ammonium surfactant, and effectively used as a dual-porogenic template to synthesize hierarchical MTW zeolite. Upon a range of synthesis parameter optimizations, our detailed characterization suggested that the hierarchical MTW zeolite would completely crystallize within 36 hours from the surface to the inside of quasi-spherical particles through in situ consumption of amorphous silicon and aluminum species; much faster than most of the hierarchical MTW zeolites generated by conventional methods. Moreover, the as-prepared hierarchical MTW zeolite exhibited 4 times higher catalytic performance and lifetime of benzene-propene alkylation compared to conventional MTW zeolite, while the introduced crystalline mesopores are of benefit to diffuse reactants, products, and coke depositions. Our strategy broadens the design of new templates in more effective ways to facilely synthesize versatile hierarchical zeolites for diverse applications, especially for those in which macromolecules are involved.

Racial disparities in kidney transplant waitlist appearance in Chicago: Is it race or place?

BACKGROUND: Prior work has demonstrated how neighborhood poverty and racial composition impact racial disparities in access to the deceased donor kidney transplant waitlist, both nationally and regionally. We examined the association between neighborhood characteristics and racial disparities in time to transplant waitlist in Chicago, a diverse city with continued neighborhood segregation. METHODS: Using data from the United States Renal Data System (USRDS) and the US Census, we investigated time from dialysis initiation to kidney transplant waitlisting for African American and white patients in Chicago using cause-specific proportional hazards analyses, adjusting for individual sociodemographic and clinical characteristics, as well as neighborhood poverty and racial composition. RESULTS: In Chicago, African Americans are significantly less likely than whites to appear on the renal transplant waitlist (HR 0.73, P < .05). Compared to whites in nonpoor neighborhoods, African Americans in poor neighborhoods are significantly less likely to appear on the transplant waitlist (HR 0.61, P < .05). Over 69% of African Americans with ESRD live in these neighborhoods. CONCLUSIONS: Consistent with national data, African Americans in Chicago have a lower likelihood of waitlisting than whites. This disparity is explained in part by neighborhood poverty, which impacts the majority of African American ESRD patients in Chicago.

Dampness Can Promote the Influenza A Virus and Worsen Its Prognosis by Upregulating the TLR7 Signaling Pathway.

Context • Outbreaks of the influenza A virus (IAV) are increasingly recognized as a global public health issue, affecting a large proportion of the world's population. A number of studies have provided epidemiologic evidence that dampness and mold are consistently associated with multiple allergic and respiratory effects, but they focused on dampness-related pathogenic microorganisms leading to allergy rather than the dampness itself. Objective • The current study intended to examine the effects of a damp environment on the promotion of the IAV and determine the adverse effects on its prognosis through upregulation of the toll-like receptor 7 (TLR7)-signaling pathway in the lung. Design • The research team performed an animal study. Setting • The study was performed at Jinan University (Guangzhou, China). Animals • A total of 144 specific-pathogen-free, C57BL/6j mice were included in the study, divided into 6 groups with 24 mice in each group. Intervention • The mice were randomly divided into the 6 groups, with 24 mice in each group: (1) group A: normal mice, a control group; (2) group B: normal mice living in a damp environment, a second control group; (3) group C: virally infected mice living in a normal environment; (4) group D: virally infected mice living in a damp environment; (5) group E: virally infected mice living in a normal environment and receiving treatment with 0.2 mL/d of 0.78 mg/mL oseltamivir; and (6) group F: virally infected mice living in a damp environment and receiving treatment with 0.2 mL/d of 0.78 mg/mL oseltamivir. Outcome Measures • Real-time quantitative polymerase chain reaction was used to measure the mRNA expression of TLR7, myeloid differentiation primary response gene 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6), interleukin 1 receptor-associated kinase 4 (IRAK4), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the TLR7 signaling pathway and the viral replication level in the lung. Results • The mice began to lose weight after being infected with IAV, especially those mice in groups D and F, where the mice were lost weight more quickly than those in groups C and E. The damages in group F were more serious than for mice in group E. In groups C and D, the mRNA TLR7, MyD88, TRAF6, IRAK4, and NF-κB were upregulated after viral infection (P < .01). After the IAV infection, the expression of TLR7, MyD88, TRAF6, and NF-κB mRNA in group D was higher (P < .01) than in group C. The oseltamivir treatment reduced the mRNA expression in the TLR7 signaling pathways (P < .01), both in the damp environment and normal environment. The expression of mRNA in the TLR7 signaling pathways was lower in group F than in group E (P < .01). Conclusions • The study suggests that dampness can promote the IAV infection and worsen its prognosis by upregulating the TLR7 signaling pathway.

QUADRO: A SUPERVISED DIMENSION REDUCTION METHOD VIA RAYLEIGH QUOTIENT OPTIMIZATION.

We propose a novel Rayleigh quotient based sparse quadratic dimension reduction method-named QUADRO (Quadratic Dimension Reduction via Rayleigh Optimization)-for analyzing high-dimensional data. Unlike in the linear setting where Rayleigh quotient optimization coincides with classification, these two problems are very different under nonlinear settings. In this paper, we clarify this difference and show that Rayleigh quotient optimization may be of independent scientific interests. One major challenge of Rayleigh quotient optimization is that the variance of quadratic statistics involves all fourth cross-moments of predictors, which are infeasible to compute for high-dimensional applications and may accumulate too many stochastic errors. This issue is resolved by considering a family of elliptical models. Moreover, for heavy-tail distributions, robust estimates of mean vectors and covariance matrices are employed to guarantee uniform convergence in estimating non-polynomially many parameters, even though only the fourth moments are assumed. Methodologically, QUADRO is based on elliptical models which allow us to formulate the Rayleigh quotient maximization as a convex optimization problem. Computationally, we propose an efficient linearized augmented Lagrangian method to solve the constrained optimization problem. Theoretically, we provide explicit rates of convergence in terms of Rayleigh quotient under both Gaussian and general elliptical models. Thorough numerical results on both synthetic and real datasets are also provided to back up our theoretical results.

Association between Ambient Air Pollution and Hospital Emergency Admissions for Respiratory and Cardiovascular Diseases in Beijing: a Time Series Study.

OBJECTIVE: To investigate the association between ambient air pollution and hospital emergency admissions in Beijing. METHODS: In this study, a semi-parametric generalized additive model (GAM) was used to evaluate the specific influences of air pollutants (PM10, SO2, and NO2) on hospital emergency admissions with different lag structures from 2009 to 2011, the sex and age specific influences of air pollution and the modifying effect of seasons on air pollution to analyze the possible interaction. RESULTS: It was found that a 10 µg/m3 increase in concentration of PM10 at lag 03 day, SO2 and NO2 at lag 0 day were associated with an increase of 0.88%, 0.76%, and 1.82% respectively in overall emergency admissions. A 10 µg/m3 increase in concentration of PM10, SO2 and NO2 at lag 5 day were associated with an increase of 1.39%, 1.56%, and 1.18% respectively in cardiovascular disease emergency admissions. For lag 02, a 10 µg/m3 increase in concentration of PM10, SO2 and NO2 were associated with 1.72%, 1.34%, and 2.57% increases respectively in respiratory disease emergency admissions. CONCLUSION: This study further confirmed that short-term exposure to ambient air pollution was associated with increased risk of hospital emergency admissions in Beijing.

Safety Evaluation, in Vitro and in Vivo Antioxidant Activity of the Flavonoid-Rich Extract from Maydis stigma.

This study aimed to assess the acute toxicity and safety of flavonoid-rich extract from Maydis stigma (FMS) in mice. The in vitro antioxidant activity of FMS was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethyl-benzthiazoline-6-sulphonate) (ABTS) scavenging assays. Furthermore, the in vivo antioxidant of FMS against ethanol-induced oxidative damage in mice was determined by analysis of the serum total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, liver tissue glutathione (GSH) content, and protein carbonyl (PC) content in liver tissue. The oral administration of FMS at doses of 30 g/kg did not cause death in mice, and there were no significant biologically adverse effects in mice. These results indicated that the median lethal dose (LD50) is higher than this dose. The IC50 values of FMS for the DPPH and ABTS scavenging activity were 50.73 and 0.23 mg/mL, respectively. Meanwhile, FMS could significantly enhance T-SOD activity, reduce MDA content in the serum, increase GSH content, and decrease PC content in the liver tissue at the tested doses (25, 50, 100, 200 mg/kg·day). These results indicate that FMS can be generally regarded as safe and used potentially as a bioactive source of natural antioxidants.

Identification of an MHC class I ligand for the single member of a killer cell lectin-like receptor family, KLRH1.

Natural killer cells are able to recognize and kill target cells according to differences in MHC class I expression. In rodents, the Ly49 receptors are primarily responsible for this MHC differentiation. We previously described the cloning of a novel C-type lectin-like receptor, KLRH1, encoded in the NK complex adjacent to the Ly49 genes and expressed by subsets of NK and NKT cells. MHC influence on selection of KLRH1(+) NK cells in congenic strains suggested that KLRH1 may have an MHC ligand, although we were unable to identify any such ligand. In this study, we have used a sensitive reporter system and Fc fusion protein to demonstrate that KLRH1 binds specifically to the classical MHC class I molecule RT1-A2 of the RT1(n) haplotype. Cytolytic activity of KLRH1-transfected RNK-16 cells was also inhibited by target cells expressing RT1-A2(n). Thus, KLRH1 represents a novel family of MHC allele-specific inhibitory receptors expressed by NK cells.

Silk-based intelligent fibers and textiles: structures, properties, and applications.

Multifunctional fibers represent a cornerstone of human civilization, playing a pivotal role in numerous aspects of societal development. Natural biomaterials, in contrast to synthetic alternatives, offer environmental sustainability, biocompatibility, and biodegradability. Among these biomaterials, natural silk is favored in biomedical applications and smart fiber technology due to its accessibility, superior mechanical properties, diverse functional groups, controllable structure, and exceptional biocompatibility. This review delves into the intricate structure and properties of natural silk fibers and their extensive applications in biomedicine and smart fiber technology. It highlights the critical significance of silk fibers in the development of multifunctional materials, emphasizing their mechanical strength, biocompatibility, and biodegradability. A detailed analysis of the hierarchical structure of silk fibers elucidates how these structural features contribute to their unique properties. The review also encompasses the biomedical applications of silk fibers, including surgical sutures, tissue engineering, and drug delivery systems, along with recent advancements in smart fiber applications such as sensing, optical technologies, and energy storage. The enhancement of functional properties of silk fibers through chemical or physical modifications is discussed, suggesting broader high-end applications. Additionally, the review addresses current challenges and future directions in the application of silk fibers in biomedicine and smart fiber technologies, underscoring silk's potential in driving contemporary technological innovations. The versatility and sustainability of silk fibers position them as pivotal elements in contemporary materials science and technology, fostering the development of next-generation smart materials.

The effects of training intensities on motor recovery and gait symmetry in a rat model of ischemia.

PRIMARY OBJECTIVE: This study investigated the effects of moderate and excessive gait training intensities on motor recovery in sub-acute stroke. METHODS: Sprague-Dawley rats after stroke surgery were randomized into two groups: moderate training group (MTG) and excessive training group (ETG). MTG had 15 minutes of body weight support (BWS) treadmill training per session with three sessions per day on alternative days until 8 days after stroke; and in the ETG, rats had to run until they could not keep up with the treadmill speed for one session on each training day. The intramuscular EMG signal from medial gastrocnemius was used to monitor the muscle activation patterns on both unaffected and affected sides during training. RESULTS: After 4 days post-stroke, the results showed a better recovery in the symmetry gait pattern in the MTG, but there is no such trend observed in the ETG. Moreover, the MTG has a better motor behaviour score and the affected side could bear more body weight. These results were reflected in the increase in the EMG burst duration and increase in EMG mean power frequency (MPF) drop rate on the affected side in the MTG. CONCLUSION: This study shows the moderate gait training intensity by avoiding muscular fatigue has better motor recovery for sub-acute stroke rehabilitation.

[A feasibility research of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using hybrid internal fixation for recurrent lumbar disc herniation].

OBJECTIVE: To investigate the feasibility of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using hybrid internal fixation of pedicle screws and a translaminar facet screw for recurrent lumbar disc herniation. METHODS: From January 2010 to December 2011, 16 recurrent lumbar disc herniation patients, 10 male and 6 female patients with an average age of 45 years (35-68 years) were treated with unilateral incision MIS-TLIF through working channel. After decompression, interbody fusion and fixation using unilateral pedicle screws, a translaminar facet screw was inserted from the same incision through spinous process and laminar to the other side facet joint. The results of perioperative parameters, radiographic images and clinical outcomes were assessed. The repeated measure analysis of variance was applied in the scores of visual analogue scale (VAS) and Oswestry disablity index (ODI). RESULTS: All patients MIS-TLIF were accomplished under working channel including decompression, interbody fusion and hybrid fixation without any neural complication. The average operative time was (148 ± 75) minutes, the average operative blood loss was (186 ± 226) ml, the average postoperative ambulation time was (32 ± 15) hours, and the average hospitalization time was (6 ± 4) days. The average length of incision was (29 ± 4) mm, and the average length of translaminar facets screw was (52 ± 6) mm. The mean follow-up was 16.5 months with a range of 12-24 months. The postoperative X-ray and CT images showed good position of the hybrid internal fixation, and all facets screws penetrate through facets joint. The significant improvement could be found in back pain VAS, leg pain VAS and ODI scores between preoperative 1 day and postoperative follow-up at all time-points (back pain VAS:F = 52.845, P = 0.000;leg pain VAS:F = 113.480, P = 0.000;ODI:F = 36.665, P = 0.000). CONCLUSION: Recurrent lumbar disc herniation could be treated with MIS-TLIF using hybrid fixation through unilateral incision, and the advantage including less invasion and quickly recovery.

Subject clustering by IF-PCA and several recent methods.

Subject clustering (i.e., the use of measured features to cluster subjects, such as patients or cells, into multiple groups) is a problem of significant interest. In recent years, many approaches have been proposed, among which unsupervised deep learning (UDL) has received much attention. Two interesting questions are 1) how to combine the strengths of UDL and other approaches and 2) how these approaches compare to each other. We combine the variational auto-encoder (VAE), a popular UDL approach, with the recent idea of influential feature-principal component analysis (IF-PCA) and propose IF-VAE as a new method for subject clustering. We study IF-VAE and compare it with several other methods (including IF-PCA, VAE, Seurat, and SC3) on 10 gene microarray data sets and eight single-cell RNA-seq data sets. We find that IF-VAE shows significant improvement over VAE, but still underperforms compared to IF-PCA. We also find that IF-PCA is quite competitive, slightly outperforming Seurat and SC3 over the eight single-cell data sets. IF-PCA is conceptually simple and permits delicate analysis. We demonstrate that IF-PCA is capable of achieving phase transition in a rare/weak model. Comparatively, Seurat and SC3 are more complex and theoretically difficult to analyze (for these reasons, their optimality remains unclear).

Eldecalcitol prevents muscle loss and osteoporosis in disuse muscle atrophy via NF-κB signaling in mice.

We investigated the effect of eldecalcitol on disuse muscle atrophy. C57BL/6J male mice aged 6 weeks were randomly assigned to control, tail suspension (TS), and TS-eldecalcitol-treated groups and were injected intraperitoneally twice a week with either vehicle (control and TS) or eldecalcitol at 3.5 or 5 ng for 3 weeks. Grip strength and muscle weights of the gastrocnemius (GAS), tibialis anterior (TA), and soleus (SOL) were determined. Oxidative stress was evaluated by malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase. Bone microarchitecture was analyzed using microcomputed tomography. The effect of eldecalcitol on C2C12 myoblasts was analyzed by measuring myofibrillar protein MHC and the atrophy markers Atrogin-1 and MuRF-1 using immunofluorescence. The influence of eldecalcitol on NF-κB signaling pathway and vitamin D receptor (VDR) was assessed through immunofluorescence, (co)-immunoprecipitation, and VDR knockdown studies. Eldecalcitol increased grip strength (P < 0.01) and restored muscle loss in GAS, TA, and SOL (P < 0.05 to P < 0.001) induced by TS. An improvement was noted in bone mineral density and bone architecture in the eldecalcitol group. The impaired oxidative defense system was restored by eldecalcitol (P < 0.05 to P < 0.01 vs. TS). Eldecalcitol (10 nM) significantly inhibited the expression of MuRF-1 (P < 0.001) and Atrogin-1 (P < 0.01), increased the diameter of myotubes (P < 0.05), inhibited the expression of P65 and P52 components of NF-κB and P65 nuclear location, thereby inhibiting NF-κB signaling. Eldecalcitol promoted VDR binding to P65 and P52. VDR signaling is required for eldecalcitol-mediated anti-atrophy effects. In conclusion, eldecalcitol exerted its beneficial effects on disuse-induced muscle atrophy via NF-κB inhibition.