The Heterogeneous Cellular States of Glioblastoma Stem Cells Revealed by Single Cell Analysis.

Glioblastoma stem cells (GSCs) contributed to the progression, treatment resistance, and relapse of glioblastoma (GBM). However, current researches on GSCs were performed usually outside the human tumor microenvironment, ignoring the importance of the cellular states of primary GSCs. In this study, we leveraged single-cell transcriptome sequencing data of 6 independent GBM cohorts from public databases, and combined lineage and stemness features to identify primary GSCs. We dissected the cell states of GSCs and correlated them with the clinical outcomes of patients. As a result, we constructed a cellular hierarchy where GSCs resided at the center. In addition, we identified and characterized 2 different and recurrent GSCs subpopulations: proliferative GSCs (pGSCs) and quiescent GSCs (qGSCs). The pGSCs showed high cell cycle activity, indicating rapid cell division, while qGSCs showed a quiescent state. Then we traced the processes of tumor development by pseudo-time analysis and tumor phylogeny, and found that GSCs accumulated throughout the whole tumor development period. During the process, pGSCs mainly contributed to the early stage and qGSCs were enriched in the later stage. Finally, we constructed an 8-gene prognostic signature reflecting pGSCs activity and found that patients whose tumors were enriched for the pGSC signature had poor clinical outcomes. Our study highlights the primary GSCs heterogeneity and its correlation to tumor development and clinical outcomes, providing the potential targets for GBM treatment.

Progressive acceleration in the genetic algorithm by intragenerational mutation.

The intragenerational mutation of the genetic algorithm (IMGA) is proposed to actively broaden the searching space during the optimization process. The searching space is aggressively increased by expanding the variation of mutation rates of all individuals within each generation, leading to the reduction of the required number of iterations, improving the convergence speed and the enhancement factor.

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OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

RNA kinase CLP1/Cbc regulates meiosis initiation in spermatogenesis.

CLP1, TSEN complex, and VCP are evolutionarily conserved proteins whose mutations are associated with neurodegenerative diseases. In this study, we have found that they are also involved in germline differentiation. To optimize both quantity and quality in gametes production, germ cells expand themselves through limited mitotic cycles prior to meiosis. Stemming from our previous findings on the correlation between mRNA 3'-processing and meiosis entry, here we identify that the RNA kinase Cbc, the Drosophila member of the highly conserved CLP1 family, is a component of the program regulating the transition from mitosis to meiosis. Using genetic manipulations in Drosophila testis, we demonstrate that nuclear Cbc is required to promote meiosis entry. Combining biochemical and genetic methods, we reveal that Cbc physically and/or genetically intersects with Tsen54 and TER94 (VCP ortholog) in this process. The C-terminal half of Tsen54 is both necessary and sufficient for its binding with Cbc. Further, we illustrate the functional conservation between Cbc and mammalian CLP1 in the assays of subcellular localization and Drosophila fertility. As CLP1, TSEN complex, and VCP have also been identified in neurodegenerations of animal models, a mechanism involving these factors seems to be shared in gametogenesis and neurogenesis.

Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis.

BACKGROUND: Cellular states of different immune cells can affect the activity of the whole immune microenvironment. METHODS: Here, leveraging reference profiles of microenvironment cell states that were constructed based on single-cell RNA-seq data of melanoma, we dissected the composition of microenvironment cell states across 463 skin cutaneous melanoma (SKCM) bulk samples through CIBERSORT-based deconvolution of gene expression profiles and revealed high heterogeneity of their distribution. Correspondence analysis on the estimated cellular fractions of melanoma bulk samples was performed to identify immune phenotypes. Based on the publicly available clinical survival and therapy data, we analyzed the relationship between immune phenotypes and clinical outcomes of melanoma. RESULTS: By analysis of the relationships among those cell states, we further identified three distinct tumor microenvironment immune phenotypes: "immune hot/active", "immune cold-suppressive" and "immune cold-exhausted". They were characterized by markedly different patterns of cell states: most notably the CD8 T Cytotoxic state, CD8 T Mixed state, B non-regulatory state and cancer-associated fibroblasts (CAFs), depicting distinct types of antitumor immune response (or immune activity). These phenotypes had prognostic significance for progression-free survival and implications in response to immune therapy in an independent cohort of anti-PD1 treated melanoma patients. CONCLUSIONS: The proposed strategy of leveraging single-cell data to dissect the composition of microenvironment cell states in individual bulk tumors can also extend to other cancer types, and our results highlight the importance of microenvironment cell states for the understanding of tumor immunity.

Clinical characteristics of infants hospitalized with early congenital syphilitic nephropathy: a single-center retrospective cross-sectional study in China.

BACKGROUND: Early studies claimed that early congenital syphilitic (CS) nephropathy was rare, and systematic studies about this disease are absent, which may lead to poor awareness of early CS nephropathy in clinicians and result in misdiagnosis and poor patient prognosis. The present study systematically and comprehensively analyzes the clinical characteristics of infants with early CS nephropathy hospitalized in Beijing Ditan Hospital, an infectious disease hospital in China in order to improve the understanding and management of this disorder. METHODS: Data of the children with early CS from July 1, 2008, to December 31, 2021, were collected from the electronic medical record system of the hospital. Each patient's demographic characteristics, clinical history, mother's history of syphilitic infection, and laboratory values were extracted. The patients were enrolled to either the nephropathy group or the non-nephropathy group depending on diagnosis. Descriptive statistics was used to report basic demographics, clinical and laboratory test values, and variables were compared between the two groups by nonparametric tests, t test or χ2 tests. RESULTS: Of the 122 children with early CS enrolled, 24(19.7%) were diagnosed with early CS nephropathy. All of the children with CS nephropathy were young infants < 6 months old. A majority of them showed typical congenital syphilitic skin lesions, but a quarter of them did not have skin lesions. Compared with non-nephropathic children with early CS, those with nephropathy had higher frequency of hepatosplenomegaly, fever, edema, gastrointestinal (GI) symptoms, and anemia, as well as decreased C3 levels. Urinalysis results showed hematuria in all patients with early CS nephropathy, with proteinuria and renal function impairment in 91.7% and 12.5% of the patients, respectively. Nephritic-type nephrotic syndrome and glomerulonephritis were diagnosed in 45.8% and 54.2% of these patients, respectively. All infants with CS nephropathy were cured or improved after appropriate treatments. CONCLUSION: Infants with early CS nephropathy often presented with nephritic-type nephrotic syndrome or glomerulonephritis, and the typical skin lesions, fever, hepatosplenomegaly, and edema, etc., were its common clinical presentations, and these characteristics could help with the diagnosis. But for infants with nephropathy who did not have typical clinical presentations, CS should also be screened as an important etiology to avoid misdiagnosis.

Speedy light focusing through scattering media by a cooperatively FPGA-parameterized genetic algorithm.

We developed an accelerated Genetic Algorithm (GA) system based on the cooperation of a field-programmable gate array (FPGA) and the optimized parameters that enables fast light focusing through scattering media. Starting at the searching space, which influences the convergence of the optimization algorithms, we manipulated the mutation rate that defines the number of mutated pixels on the spatial light modulator to accelerate the GA process. We found that the enhanced decay ratio of the mutation rate leads to a much faster convergence of the GA. A convergence-efficiency function was defined to gauge the tradeoff between the processing time and the enhancement of the focal spot. This function allowed us to adopt the shorter iteration number of the GA that still achieves applicable light focusing. Furthermore, the accelerated GA configuration was programmed in FPGA to boost processing speed at the hardware level. It shows the ability to focus light through scattering media within a few seconds, 150 times faster than the PC-based GA. The processing cycle could be further promoted to a millisecond-level with the advanced FPGA processor chips. This study makes the evolution-based optimization approach adaptable in dynamic scattering media, showing the capability to tackle wavefront shaping in biological material.

Application progress of magnetic molecularly imprinted polymers chemical sensors in the detection of biomarkers.

Specific recognition and highly sensitive detection of biomarkers play an essential role in identification, early diagnosis and prevention of many diseases. Magnetic molecularly imprinted polymers (MMIPs) have been widely used to capture biomimetic receptors for targets in various complex matrices due to their superior recognition ability, structural stability, and rapid separation characteristics, which overcome the existing deficiencies of traditional recognition elements such as antibodies, aptamers. The integration of MMIPs as recognition elements with chemical sensors opens new opportunities for the development of advanced analytical devices with improved selectivity and sensitivity, shorter analysis time, and lower cost. Recently, MMIPs-chemical sensors (MMIPs-CS) have made significant progress in detection, but many challenges and development spaces remain. Therefore, this review focuses on the research progress of the sensor based on biomarker detection and introduces the surface modification of the magnetic support material used to prepare high selective MMIPs, as well as the selective extraction of target biomarkers by MMIPs from the complex biological sample matrix. Based on the understanding of optical sensors and electrochemical sensors, the applications of MMIPs-optical sensors (MMIPs-OS) and MMIPs-electrochemical sensors (MMIPs-ECS) for biomarker detection were reviewed and discussed in detail. Moreover, it provides an overview of the challenges in this research area and the potential strategies for the rational design of high-performance MMIPs-CS, accelerating the development of multifunctional MMIPs-CS.

IDH clonal heterogeneity segregates a subgroup of non-1p/19q codeleted gliomas with unfavourable clinical outcome.

AIMS: Diffuse gliomas (DGs) are classified into three major molecular subgroups following the revised World Health Organisation (WHO) classification criteria based on their IDH mutation and 1p/19q codeletion status. However, substantial biological heterogeneity and differences in the clinical course are apparent within each subgroup, which remain to be resolved. We sought to assess the clonal status of somatic mutations and explore whether additional molecular subgroups exist within DG. METHODS: A computational framework that integrates the variant allele frequency, local copy number and tumour purity was used to infer the clonality of somatic mutations in 876 DGs from The Cancer Genome Atlas (TCGA). We performed an unsupervised cluster analysis to identify molecular subgroups and characterised their clinical and biological significance. RESULTS: DGs showed widespread genetic intratumoural heterogeneity (ITH), with nearly all driver genes harbouring subclonal mutations, even for known glioma initiating event IDH1 (17.1%). Gliomas with subclonal IDH mutation and without 1p/19q codeletion showed shorter overall and disease-specific survival, higher ITH and exhibited differences in genomic patterns, transcript levels and proliferative potential, when compared with IDH clonal mutation and no 1p/19q codeletion gliomas. We defined a refined stratification system based on the current WHO glioma molecular classification, which showed close correlations with patients' clinical outcomes. CONCLUSIONS: For the first time, we integrated the clonal status of somatic mutations into cancer genomic classification and highlighted the necessity of considering IDH clonal architectures in glioma precision stratification.

Efficacy and safety of ledipasvir/sofosbuvir for hepatitis C among drug users: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Limited data is available on the efficacy of direct acting anti-viral drugs on hepatitis C in drug users. The aim of this meta-analysis was to comprehensively analyze the efficacy and safety of LDV/SOF in drug users infected with the hepatitis C virus (HCV). METHODS: The PubMed, Cochrane library, Embase and Web of Science databases were searched for articles published till April 2021 on HCV-positive drug users who were treated with ledipasvir/sofosbuvir (LDV/SOF). The primary endpoint was pooled sustained virological response at 12 weeks (SVR12) with 95% confidence interval (95% CI). Funnel plots and Egger's test were used to assess the publication bias. RESULTS: A total of 12 studies and 711 subjects treated with LDV/SOF-based regimen for HCV were included, and the pooled SVR12 rate was 89.8% (95% CI 85.9-92.7). The pooled SVR12 rate of genotype 1 drug users was 92.4% (95% CI 88.6-95.0). Subgroup analysis showed that pooled SVR12 rates of patients treated with LDV/SOF and LDV/SOF ± RBV were 89.2% (95% CI 83.4-93.1), 90.4% (95% CI 83.6-94.5) respectively. In addition, the SVR12 rates were 88% (95% CI 70.7-95.7) for 8 weeks, 89.9% (95% CI 81.0-94.9) for 12 weeks and 82.2% (95% CI 24.9-98.5) for 24 weeks of treatment. CONCLUSION: LDV/SOF is a safe and relatively effective treatment for hepatitis C in drug users.

An analysis of the clinical features of children with early congenital Syphilis and Syphilitic Hepatitis.

BACKGROUND: The infection rate of congenital syphilis is gradually increasing, the clinical manifestations of some children with congenital syphilis are abnormal liver function, which is given the clinical diagnosis of syphilitic hepatitis. At present, there are few studies on the clinical features of children with early congenital syphilis combined with syphilitic hepatitis, so we set out to do such a study. We compared the liver function indicators before and after the treatment of syphilis to find the clinical features that can provide guidance for clinical diagnosis and treatment. METHODS: This study collected clinical data on 51 children with early congenital syphilis combined with syphilitic hepatitis in Beijing Ditan Hospital, affiliated with Capital Medical University, between April 2014 and October 2019. We observed their age, gender, clinical symptoms, and physical symptoms, as well as the pregnancy and childbirth history of their mothers. We also compared the liver function indicators before and after the treatment of the syphilis and analyzed the children's clinical features. RESULTS: The results of this study showed that the clinical manifestations in children with early congenital syphilis combined with syphilitic hepatitis were diverse. The most common clinical manifestation was anemia (56.9 %), followed by syphilitic rash (54.9 %), hands, feet, and whole-body peeling (35.3 %), and splenomegaly (29.4 %). Liver damage caused by a syphilis infection tends to result in elevated alanine aminotransferase, aspartate aminotransferase, and bilirubin, while albumin decreases. After the syphilis treatment, the liver function indexes were significantly improved compared with before treatment, and the difference was statistically significant (all p < 0.05). CONCLUSIONS: A child with abnormal liver function, especially with anemia, skin rash, peeling, abdominal distension, and hepatosplenomegaly should be highly suspected of having a syphilis infection. Once the diagnosis is made, the appropriate standard penicillin treatment should be started as soon as possible to improve the condition and prognosis of the child.

Analysis of clinical characteristics of severe pertussis in infants and children: a retrospective study.

BACKGROUND: The incidence of pertussis shows an increasing trend in recent years, but some clinicians often lack sufficient understanding of the clinical characteristics and risk factors for severe pertussis, and more effective measures should be taken to reduce the incidence and mortality of pertussis in young infants METHODS: A retrospective study was conducted, and 184 infants and children with pertussis who had been hospitalized in the Department of Pediatrics of Beijing Ditan Hospital affiliated with Capital Medical University from January 2016 to December 2017 were included. Clinical data of the patients were collected and the clinical characteristics were statistically analyzed RESULTS: Among the 184 patients, 41.85% were infants < 3 months of age, and 65.22% of the total patients were not vaccinated against pertussis. There were 22 critically ill children, among whom 4 died, and compared with mild cases, they had a higher proportion of children younger than 3 months of age and infants not vaccinated against pertussis (63.64% vs. 38.89% and 100% vs. 60.49%, respectively); a higher proportion of children with severe pneumonia (100% vs. 0%); higher leukocyte count(× 109/L , 35.80 ± 20.53 vs 19.41 ± 8.59); and a higher proportion of children with severe hyperleukocytosis (18.18% vs. 0%, respectively) (P<0.05) CONCLUSIONS: 1. Infants aged <3 months not vaccinated for pertussis appear more likely to become infected and have more severe disease. 2. Severe pneumonia and hyperleukocytosis are the main mechanisms underlying severe pertussis.

Identifying bifurcated paths with differential function impact in glioblastomas evolution.

The evolutionary dynamics of human cancers has been investigated popularly and several bifurcated paths in cancer evolutionary trajectories are revealed to be with differential outcomes and phenotypes. However, whether such bifurcated paths exist in glioblastoma (GBM) remains unclear. In 385 GBM samples, through determining the clonal status of cancer driver events and inferring their temporal order, we constructed a temporal map of evolutionary trajectories at the patient population level. By investigating the differential impact on clinical outcome, we identified four key bifurcated paths, namely, "chromosome 10 copy number loss (ie, 10 loss) → chromosome 19 copy number gain (ie, 19 gain): 10 loss → 13q loss"; "10 loss → 19 gain: 10 loss → 15q loss"; "10 loss → 19 gain: 10 loss → 6q loss" and "10 loss → 19 gain: 10 loss → 16q loss". They formed a core multibranches path, with 10 loss being regarded as the common earliest event followed by 19 gain and four other departure events (13q loss, 15q loss, 6q loss and 16q loss), which may account for their difference in genome instability and patient survival time. Compared to "10 loss → 19 gain", the patients with "10 loss → 13q loss" had higher telomerase activity. Notably, there were obvious discrepancies in immune activity and immune cell infiltration level between patients with "10 loss → 13q/16q loss" and "10 loss → 19 gain", highlighting the bifurcated paths' effect on tumor immune microenvironment. In summary, our study identifies four key bifurcated paths in GBM for the first time, suggesting the feasibility of patient stratification and prognosis prediction based on key bifurcated paths.

Asymmetric chiroptical effect from chiral medium filled golden slit grating on substrate.

In this Letter, we report a giant and robust asymmetric chiroptical effect (ACOE) in the chiral medium filled golden slit grating on glass substrate (CMGSG-GS). This ACOE comes from the influence of interface asymmetry on the electromagnetic cross-coupling in the CMGSG-GS, and it is inherently different than that reported in the Faraday medium and the planar anisotropic chiral metamaterials. Both the polarization eigenstate and the transmission matrix are highly dependent on the metal structure used in the CMGSG-GS. The polarization eigenstates of the CMGSG-GS are two co-rotating elliptical states with ellipticity of nearly 0, and they remain mostly unchanged for opposite directions. The transmission matrices of opposite directions are normal matrices, which do not show any symmetric law although the geometry of the CMGSG-GS owns a high rotational symmetry. The reported ACOE gives a measurable physical parameter to reveal the events happening at interface.

Rapid Diagnosis of a Family Cluster of Pertussis Starting from a Child: a Case Report.

BACKGROUND: Pertussis, caused by Bordetella pertussis (B. pertussis), is a highly transmissible, acute respiratory disease that occurs in many countries. Diagnosis of pertussis continues to be a challenge using traditional tests due to their turn-around time and sensitivity. Herein, we rapidly and accurately screened a family cluster of pertussis from a child and her mother. METHODS: We used an automated nested multiplex PCR system which included B. pertussis, influenza A virus, and 19 other respiratory pathogens. RESULTS: We detected B. pertussis, influenza A virus H1-2009 (FluA-2009), adenovirus, and respiratory syncytial virus (RSV) in the child, and the mother of the child was positive for B. pertussis and FluA-2009. CONCLUSIONS: Active and timely screening for pertussis of adult family members should be considered. The detection of multiple respiratory pathogens may guide effective antibiotic therapies. This could be a novel test for the prevention of pertussis.

Cooperative genomic alteration network reveals molecular classification across 12 major cancer types.

The accumulation of somatic genomic alterations that enables cells to gradually acquire growth advantage contributes to tumor development. This has the important implication of the widespread existence of cooperative genomic alterations in the accumulation process. Here, we proposed a computational method HCOC that simultaneously consider genetic context and downstream functional effects on cancer hallmarks to uncover somatic cooperative events in human cancers. Applying our method to 12 TCGA cancer types, we totally identified 1199 cooperative events with high heterogeneity across human cancers, and then constructed a pan-cancer cooperative alteration network. These cooperative events are associated with genomic alterations of some high-confident cancer drivers, and can trigger the dysfunction of hallmark associated pathways in a co-defect way rather than single alterations. We found that these cooperative events can be used to produce a prognostic classification that can provide complementary information with tissue-of-origin. In a further case study of glioblastoma, using 23 cooperative events identified, we stratified patients into molecularly relevant subtypes with a prognostic significance independent of the Glioma-CpG Island Methylator Phenotype (GCIMP). In summary, our method can be effectively used to discover cancer-driving cooperative events that can be valuable clinical markers for patient stratification.

Biological evaluation and energetic analyses of novel GSK-3ß inhibitors.

Glycogen synthase kinase-3 beta (GSK-3ß) is involved in multiple signaling pathways. Consistent with its critical roles in normal cells, abnormalities in GSK-3ß activity have been implicated in diabetes, heart disease, Parkinson disease, and Alzheimer's disease. In this study, a series of new scaffolds of small molecule inhibitors of GSK-3ß were identified by virtual screening and bioassay. Candidates that adhere to drug-like criteria from a virtual library of compounds were tested using computational docking studies. Twenty selected compounds were tested, which led to the discovery of two hits. Compound 14 (IC50 = 8.48 µM) and compound 19 (IC50 = 2.19 µM) were identified with high affinity. Molecular dynamics (MD) simulations, in conjunction with molecular mechanics/Poisson-Boltzmann surface area binding free-energy analysis, were employed to gain insight into the binding modes and energetics of GSK-3ß inhibitors. The detailed analysis of molecular dynamics results shows that Ile62, Val70, Tyr134, and Leu188 in GSK-3ß are key residues responsible to the binding of compound 14 and compound 19. Importantly, our results also validated this combined virtual screening and biophysical technique approach to discovery kinase inhibitors, which may be applied for future inhibitor discovery work for GSK-3ß.

Unique manifestations and risk factors of Jarisch-Herxheimer reaction during treatment of child congenital syphilis.

OBJECTIVES: The objective of this retrospective study was to summarise the clinical manifestations of, and to analyse the incidence and risk factors of, Jarisch-Herxheimer reaction (JHR) during the treatment of children with symptomatic congenital syphilis. METHODS: Clinical data of 60 children with clinically and laboratory diagnosed congenital syphilis, hospitalised in Beijing Ditan Hospital between January 2010 and November 2015, were collected and analysed. RESULTS: A total of 11 patients with congenital syphilis (11/60, 18.3%) developed JHR. JHR occurred in 1-6 hour after the first dose of penicillin. Common clinical manifestations included fever (11/11, 100%), irritability (11/11, 100%), rapid pulse and breathing (11/11, 100%), exacerbation of existing rash (5/11, 45.6%) and chills (3/11, 27.3%). Of the 11 patients who developed JHR, 9 patients (9/11, 81.8%) had bone syphilis, 10 (10/11, 90.9%) had more than three organs affected by syphilis and 10 (10/11, 90.9%) had a high plasma concentration of rapid plasma reagin (RPR) (≥1:256); these percentages were significantly higher than in patients who had not developed JHR (p<0.05), suggesting that the occurrence of JHR was related to bone syphilis, having more than three organs affected by syphilis and a high plasma concentration of RPR. CONCLUSIONS: Clinicians should be familiar with the risk factors for this reaction and its common clinical manifestations.

Binary wavefront optimization using a simulated annealing algorithm.

We propose an idea using a simulated annealing algorithm for amplitude modulation to focus light through disordered media. Using 4096 independently controlled segments of an incident wavefront, the intensity of the target signal is enhanced 73 times over the original intensity of the same output channel. The simulated annealing algorithm and existing amplitude control algorithms for focusing through scattering media are compared experimentally. It is found that the simulated annealing algorithm achieves the highest enhancement when the number of iterations required for optimization is the same.

Cost-effectiveness of Different Intra-articular Drug Injections on Wrist and/or Elbow Compromise in Patients With Established Rheumatoid Arthritis: Short-term Results of an Open Observational Evaluation.

BACKGROUND: Intra-articular (IA) injections are an integral part of the management of rheumatoid arthritis (RA). However, there are few reports regarding the association between drug effectiveness and cost. OBJECTIVES: The aim of this study was to assess the cost-effectiveness of various combinations of IA injections of betamethasone, hyaluronic acid (HA) or etanercept for oligoarthritis in RA. METHODS: Seventy RA patients were assigned to 4 groups according to the IA injection drug(s): betamethasone alone, betamethasone + etanercept, betamethasone + HA, or etanercept alone. Data for the following were collected before and after IA injection: erythrocyte sedimentation rate, C-reactive protein (CRP), disease activity score in 28 joints calculated with CRP, and patient global visual analog scale. In addition, power Doppler ultrasonography and gray-scale ultrasonography scores were obtained for synovitis, and passive range of motion of joints was measured. RESULTS: Sixty-eight RA patients completed the trial. Compared with patients given etanercept alone, the visual analog scale, power Doppler ultrasonography, and gray-scale ultrasonography scores of each of the other groups were significantly better at each time point. At 1 month, the passive range of motion of joints in patients given betamethasone + HA was significantly better than that of each of the other groups. Synovial hyperplasia improved significantly in all groups, but less so in those given etanercept alone. All other clinical parameters of the 4 groups were similar. The costs per joint for the betamethasone-alone, betamethasone + etanercept, betamethasone + HA, and etanercept-alone groups were, respectively, $7.55, $181.77, $42.68, and $174.22. CONCLUSIONS: Intra-articular injection of betamethasone alone was the most cost-effective treatment for oligoarthritis of RA. Betamethasone combined with HA injection resulted in the best improvement in joint function.