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Jian-Feng Li,1 Guang-Lei Tian,2 Hui Pan,3 Wen-Tong Zhang,1 Da-Cun Li,1 Jing-Da Liu,1 Liang Zhao,1 Hai-Lei Li1 1Department of Hand Surgery, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, Beijing, 101300, People’s Republic of China; 2Department of Hand Surgery, Beijing Jishuitan Hospital; Peking University Fourth School of Clinical Medicine, Beijing, 100035, People’s Republic of China; 3Department of Pathology, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, Beijing, 101300, People’s Republic of ChinaCorrespondence: Jian-Feng LiDepartment of Hand Surgery, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, No. 3 Guangming South Street, Shunyi District, Beijing, 101300, People’s Republic of China, Tel +86 10 69423220, Email drlijf27@126.comObjective: This study aimed to explore the pathogenic genes and mutation sites of macrodactyly.Methods: Whole-exome sequencing was performed on the pathological tissue and peripheral blood of 12 patients with macrodactyly who were operated in our hospital between June 2018 and May 2020. In order to conduct comprehensive bioinformatics analysis and screen the pathogenic genes of macrodactyly, the patients were divided into four groups: macrodactyly of finger group, macrodactyly of foot group, macrodactyly and syndactyly of finger group, and macrodactyly and syndactyly of foot group. The results of the whole-exome sequencing were verified using Sanger sequencing in order to clarify the pathogenic genes and mutation sites of macrodactyly, and immunohistochemical analysis of the protein signaling pathways encoded by the pathogenic genes was performed to observe the protein expression and further verify the mutant genes.Results: In the comprehensive bioinformatics analysis and Sanger verification of the whole-exome sequencing, the PIK3CA gene mutation was screened as the pathogenic gene of macrodactyly. The mutation sites were identified as the p.E542K (c.G1624A) and p.E545K (c.G1633A) sites of exon10 and the p.H1047R (c.A3140G) and p.G1049R (c.G3145C) sites of exon21. Among these, the p.G1049R (c.G3145C) locus was found in macrodactyly for the first time. The mutation of the PIK3CA gene was also found to lead to increased expression of serine-threonine kinase (AKT) in adipocytes in the PI3K-AKT-mTOR signaling pathway.Conclusion: Mutation of the PIK3CA gene leads to the enhancement of the PI3K-AKT-mTOR signaling pathway, which is the cause of macrodactyly. There is also some diversity in PIK3CA gene mutation sites.Keywords: hand deformity, foot deformity, macrodactyly, PIK3CA gene

Introduction: Methylmalonic acidemia (MMA) is a disorder of autosomal recessive inheritance, with an estimated prevalence of 1:50,000. First-tier clinical diagnostic tests often return many false positives [five false positive (FP): one true positive (TP)]. In this work, our goal was to refine a classification model that can minimize the number of false positives, currently an unmet need in the upstream diagnostics of MMA., Methods: We developed machine learning multivariable screening models for MMA with utility as a secondary-tier tool for false positives reduction. We utilized mass spectrometry-based features consisting of 11 amino acids and 31 carnitines derived from dried blood samples of neonatal patients, followed by additional ratio feature construction. Feature selection strategies (selection by filter, recursive feature elimination, and learned vector quantization) were used to determine the input set for evaluating the performance of 14 classification models to identify a candidate model set for an ensemble model development., Results: Our work identified computational models that explore metabolic analytes to reduce the number of false positives without compromising sensitivity. The best results [area under the receiver operating characteristic curve (AUROC) of 97%, sensitivity of 92%, and specificity of 95%] were obtained utilizing an ensemble of the algorithms random forest, C5.0, sparse linear discriminant analysis, and autoencoder deep neural network stacked with the algorithm stochastic gradient boosting as the supervisor. The model achieved a good performance trade-off for a screening application with 6% false-positive rate (FPR) at 95% sensitivity, 35% FPR at 99% sensitivity, and 39% FPR at 100% sensitivity., Conclusions: The classification results and approach of this research can be utilized by clinicians globally, to improve the overall discovery of MMA in pediatric patients. The improved method, when adjusted to 100% precision, can be used to further inform the diagnostic process journey of MMA and help reduce the burden for patients and their families., (© 2024. The Author(s).)

Background: Some hydatid cysts of cystic echinococcosis type 1 (CE1) lack well-defined cyst walls or distinctive endocysts, making them difficult to differentiate from simple hepatic cysts., Aim: To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries., Methods: The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region (China) from January 2018 to September 2023 were retrospectively analyzed. Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis, routine abdominal ultrasound, high-frequency ultrasound, abdominal computed tomography (CT) scan, and laparoscopy. Subsequent to the treatments, these patients underwent reexaminations at the outpatient clinic until October 2023. The evaluations included the diagnostic precision of diverse examinations, the efficacy of surgical approaches, and the incidence of CE recurrence., Results: All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan. Among them, 16 patients were preoperatively diagnosed with atypical CE1, and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound. All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy, of whom 14 patients were intraoperatively confirmed to have CE1, which was consistent with the postoperative pathological diagnosis, one patient was diagnosed with a mesothelial cyst of the liver, and the other was diagnosed with a hepatic cyst combined with local infection. Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts, 4 received aspiration sclerotherapy of hepatic cysts, and 19 received laparoscopic fenestration. These patients were intraoperatively diagnosed with simple hepatic cysts. During the follow-up period, none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices. One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space., Conclusion: Abdominal high-frequency ultrasound can detect CE1 hydatid cysts. The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Patients with hematological malignancies received multiple hypodermic injections of recombinant human granulocyte colony-stimulating factor. Procedural pain is one of the most common iatrogenic causes of pain in patients with hematological malignancies. It is also identified as the most commonly occurring problem in clinical care in the Department of Hematology and Oncology at Shenzhen University General Hospital. However, providing immediate relief from pain induced by hypodermic injection of recombinant human granulocyte colony-stimulating factor remains a major challenge. This trial aims to evaluate the safety and analgesic efficacy of a fixed nitrous oxide/oxygen mixture for patients with hematological malignancies and experiencing procedural pain caused by hypodermic injection of recombinant human granulocyte colony-stimulating factor in the department., Methods: The nitrous oxide/oxygen study is a single-center, randomized, double-blind, placebo-controlled trial involving patients with hematological malignancies who require hypodermic injections of recombinant human granulocyte colony-stimulating factor for treatment. This trial was conducted in the Hematology and Oncology Department of Shenzhen University General Hospital. A total of 54 eligible patients were randomly allocated to either the fixed nitrous oxide/oxygen mixture group (n = 36) or the oxygen group (n = 18). Neither the investigators nor the patients known about the randomization list and the nature of the gas mixture in each cylinder. Outcomes were monitored at the baseline (T0), immediately after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T1), and 5 min after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T2) for each group. The primary outcome measure was the score in the numerical rating scale corresponding to the highest level of pain experienced during hypodermic injection of recombinant human granulocyte colony-stimulating factor. Secondary outcomes included the fear of pain, anxiety score, four physiological parameters, adverse effects, total time of gas administration, satisfaction from both patients and nurses, and the acceptance of the patients., Discussion: This study focused on the safety and analgesic efficacy during hypodermic injection of recombinant human granulocyte colony-stimulating factor procedure. Data on the feasibility and safety of nitrous oxide/oxygen therapy was provided if proven beneficial to patients with hematological malignancies during hypodermic injection of recombinant human granulocyte colony-stimulating factor and widely administered to patients with procedural pain in the department., Trial Registration: Chinese Clinical Trial Register, ChiCTR2200061507. Registered on June 27, 2022. http://www.chictr.org.cn/edit.aspx?pid=170573&htm=4., (© 2024. The Author(s).)

A series of bitopic ligands based on Fallypride with a flexible secondary binding fragment (SBF) were prepared with the goal of preparing a D 3 R-selective compound. The effect of the flexible linker ( ( R , S ) -trans -2a - d ), SBFs ( ( R , S ) -trans -2h - j ), and the chirality of orthosteric binding fragments (OBFs) ( ( S , R ) -trans -d , ( S , R ) -trans -i , ( S , S ) -trans -d , ( S , S ) -trans -i, ( R , R ) -trans -d, and ( R , R ) -trans -i ) were evaluated in in vitro binding assays. Computational chemistry studies revealed that the interaction of the fragment binding to the SBF increased the distance between the pyrrolidine nitrogen and ASP110 3.32 of the D 3 R, thereby reducing the D 3 R affinity to a suboptimal level.

The difference in the secondary binding site (SBS) between the dopamine 2 receptor (D 2 R) and dopamine 3 receptor (D 3 R) has been used in the design of compounds displaying selectivity for the D 3 R versus D 2 R. In the current study, a series of bitopic ligands based on Fallypride were prepared with various secondary binding fragments (SBFs) as a means of improving the selectivity of this benzamide analog for D 3 R versus D 2 R. We observed that compounds having a small alkyl group with a heteroatom led to an improvement in D 3 R versus D 2 R selectivity. Increasing the steric bulk in the SBF increase the distance between the pyrrolidine N and Asp110, thereby reducing D 3 R affinity. The best-in-series compound was (2S,4R)-trans-27 which had a modest selectivity for D 3 R versus D 2 R and a high potency in the β-arrestin competition assay which provides a measure of the ability of the compound to compete with endogenous dopamine for binding to the D 3 R. The results of this study identified factors one should consider when designing bitopic ligands based on Fallypride displaying an improved affinity for D 3 R versus D 2 R., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The regenerative medicine has made great breakthrough in the repair of combat trauma, showing broad prospects, while the method of regenerative medicine applied in the early treatment of combat trauma is not yet clear. The early treatment of combat trauma includes strict control of bleeding, a large amount of blood transfusion, alleviation of acidosis, and correction of hypothermia and improvement of coagulation dysfunction, etc. This paper focuses on the bio-engineered blood, research and development of homeostatic materials, control of inflammation/infection, regulation of immunity, protection of important organs, establishment of military medical model, research and development of biosensors and drugs, and preventive application of stem cell bank in regenerative and tissue engineering in defense medicine to summarize the role of regenerative medicine in the early treatment of combat trauma, hoping to improve the overall treatment level of combat trauma.

Background: Emerging functional imaging studies suggest that schizophrenia is associated with aberrant spatiotemporal interaction which may result in aberrant global and local dynamic properties., Methods: We investigated the dynamic functional connectivity (FC) by using instantaneous phase method based on Hilbert transform to detect abnormal spatiotemporal interaction in schizophrenia. Based on resting-state functional magnetic resonance imaging, two independent datasets were included, with 114 subjects from COBRE [51 schizophrenia patients (SZ) and 63 healthy controls (HCs)] and 96 from OpenfMRI (36 SZ and 60 HCs). Phase differences and instantaneous coupling matrices were firstly calculated at all time points by extracting instantaneous parameters. Global [global synchrony and intertemporal closeness (ITC)] and local dynamic features [strength of FC (sFC) and variability of FC (vFC)] were compared between two groups. Support vector machine (SVM) was used to estimate the ability to discriminate two groups by using all aberrant features., Results: We found SZ had lower global synchrony and ITC than HCs on both datasets. Furthermore, SZ had a significant decrease in sFC but an increase in vFC, which were mainly located at prefrontal cortex, anterior cingulate cortex, temporal cortex and visual cortex or temporal cortex and hippocampus, forming significant dynamic subnetworks. SVM analysis revealed a high degree of balanced accuracy (85.75%) on the basis of all aberrant dynamic features., Conclusions: SZ has worse overall spatiotemporal stability and extensive FC subnetwork lesions compared to HCs, which to some extent elucidates the pathophysiological mechanism of schizophrenia, providing insight into time-variation properties of patients with other mental illnesses.

The root rot disease causes a great economic loss, and the disease severity usually increases as ginseng ages. However, it is still unclear whether the disease severity is related to changes in microorganisms during the entire growing stage of American ginseng. The present study examined the microbial community in the rhizosphere and the chemical properties of the soil in 1-4-year-old ginseng plants grown in different seasons at two different sites. Additionally, the study investigated ginseng plants' root rot disease index (DI). The results showed that the DI of ginseng increased 2.2 times in one sampling site and 4.7 times in another during the 4 years. With respect to the microbial community, the bacterial diversity increased with the seasons in the first, third, and fourth years but remained steady in the second year. The seasonal changing of relative abundances of bacteria and fungi showed the same trend in the first, third, and fourth years but not in the second year. Linear models revealed that the relative abundances of Blastococcus, Symbiobacterium, Goffeauzyma, Entoloma, Staphylotrichum, Gymnomyces, Hirsutella, Penicillium and Suillus spp. were negatively correlated with DI, while the relative abundance of Pandoraea, Rhizomicrobium, Hebeloma, Elaphomyces, Pseudeurotium, Fusarium, Geomyces, Polyscytalum, Remersonia, Rhizopus, Acremonium, Paraphaeosphaeria, Mortierella, and Metarhizium spp. were positively correlated with DI ( P < 0.05). The Mantel test showed that soil chemical properties, including available nitrogen, phosphorus, potassium, calcium, magnesium, organic matter, and pH, were significantly correlated to microbial composition. The contents of available potassium and nitrogen were positively correlated with DI, while pH and organic matter were negatively correlated with DI. In summary, we can deduce that the second year is the key period for the shift of the American ginseng rhizosphere microbial community. Disease aggravation after the third year is related to the deterioration of the rhizosphere microecosystem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bi, Zhang, Jiao, Li, Peng, Tian, Wang and Gao.)

Zeros in compositional data are very common and can be classified into rounded and essential zeros. The rounded zero refers to a small proportion or below detection limit value, while the essential zero refers to the complete absence of the component in the composition. In this article, we propose a new framework for analyzing compositional data with zero entries by introducing a stochastic representation. In particular, a new distribution, namely the Dirichlet composition distribution, is developed to accommodate the possible essential-zero feature in compositional data. We derive its distributional properties (e.g., its moments). The calculation of maximum likelihood estimates via the Expectation-Maximization (EM) algorithm will be proposed. The regression model based on the new Dirichlet composition distribution will be considered. Simulation studies are conducted to evaluate the performance of the proposed methodologies. Finally, our method is employed to analyze a dataset of fluorescence in situ hybridization (FISH) for chromosome detection., (© 2021 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

Soil sterilization integrated with agronomic measures is an effective method to reduce soilborne replant diseases. However, the effect of vermicompost or biochar application after soil sterilization on soilborne diseases is poorly understood. A pot experiment was conducted in American ginseng to investigate the effects of vermicompost (VF), biochar (BF), and a combination of vermicompost and biochar (VBF) applied after soil sterilization on the incidence of Fusarium root rot using natural recovery (F) as control. After one growing season, the disease index of root rot, the phenolic acids, and the microbial communities of American ginseng rhizosphere soil were analyzed. The disease index of VF, BF, and VBF decreased by 33.32%, 19.03%, and 80.96%, respectively, compared with F. The highest bacterial richness and diversity were observed in the rhizosphere soil of VBF. Besides, VF and VBF significantly increased the relative abundance of beneficial bacteria (Pseudomonas, Lysobacter, and Chryseolinea) in the rhizosphere soil. Higher concentrations of vanillin, one of the phenolic acids in the roots exudates, were recorded in the rhizosphere soils of BF and VBF. The vanillin concentration showed a significant negative correlation with the disease index. To conclude, vermicompost improved the beneficial bacteria of the rhizosphere soil, while biochar regulated the allelopathic effect of the phenolic acids. The study proposes a combined application of biochar and vermicompost to the rhizosphere soil to control Fusarium root rot of replanted American ginseng effectively. KEY POINTS: Vermicompost improves the relative abundance of rhizosphere beneficial bacteria. Biochar inhibits the degradation of phenolic acids by adsorption. The combination of vermicompost and biochar enhances the disease control effect., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze the clinical characteristics of 170 cases of macrodactyly., Methods: Medical records of 170 macrodactyly patients at Beijing Jishuitan Hospital between March 2006 and October 2019, including demographic characteristics, clinical presentations, anatomical distributions, X-rays, pathological findings, and treatments, were reviewed. PIK3CA mutation analyses of 12 patients were also reviewed., Results: Disease incidence was similar across sex and geographical regions. Multiple-digit involvement was 3.9 times more frequent than single-digit involvement. In upper deformit: ies, the index finger, middle finger and thumb were mostly involved, and the second and third toes were the most affected on the foot. Two digits were affected more often than three digits, with the affected multiple digits were adjacent most time. The cases of progressive macrodactyly, in which the affected digits grew at a faster rate than the unaffected digits, were found more than static type. Most of progressive macrodactyly were noticed at birth. In terms of nerve involvement, affected fingers mostly occurred in the median nerve innervation area (79.4%) accompanied by median nerve and brunches enlargement and fat infiltration, i.e., nerve territory oriented; affected toes mostly occurred in the medial plantar nerve innervation area (89.1%), marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth, i.e., lipomatous. Only 17 cases had comorbid of syndactyly. The metacarpal bones were involved only in progressive type of macrodactyly. Ten of the 12 cases subjected to PIK3CA mutation analysis were positive. Among all tested specimens, PIK3CA mutation levels ranged from 7% to 27%. In terms of tissue sources in which a mutation was found, adipose tissue had the highest mutation detection rate, followed by nerve and skin. All the DNA samples of blood from the 12 PIK3CA mutation-positive patients were negative., Conclusion: Macrodactyly fingers mostly occurred in the median nerve innervation area accompanied by median nerve and brunches enlargement and fat infiltration. The index and middle fingers were mostly involved. Macrodactyly toes mostly occurred in the medial plantar nerve innervation area, marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth. The second and third toes were the most affected on the foot. A high proportion (83%) of isolated macrodactyly patients carry activating PIK3CA mutations. Adipose, nerve, and skin tissues provide the highest PIK3CA mutation detection yield among all types of tissue studied.

In this paper, a new multivariate zero-inflated binomial (MZIB) distribution is proposed to analyse the correlated proportional data with excessive zeros. The distributional properties of purposed model are studied. The Fisher scoring algorithm and EM algorithm are given for the computation of estimates of parameters in the proposed MZIB model with/without covariates. The score tests and the likelihood ratio tests are derived for assessing both the zero-inflation and the equality of multiple binomial probabilities in correlated proportional data. A limited simulation study is performed to evaluate the performance of derived EM algorithms for the estimation of parameters in the model with/without covariates and to compare the nominal levels and powers of both score tests and likelihood ratio tests. The whitefly data is used to illustrate the proposed methodologies., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 Informa UK Limited, trading as Taylor & Francis Group.)

In this paper, we propose a new kind of multivariate t distribution by allowing different degrees of freedom for each univariate component. Compared with the classical multivariate t distribution, it is more flexible in the model specification that can be used to deal with the variant amounts of tail weights on marginals in multivariate data modeling. In particular, it could include components following the multivariate normal distribution, and it contains the product of independent t -distributions as a special case. Subsequently, it is extended to the regression model as the joint distribution of the error terms. Important distributional properties are explored and useful statistical methods are developed. The flexibility of the specified structure in better capturing the characteristic of data is exemplified by both simulation studies and real data analyses., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology. Methods: This was a retrospectively study. Newborn screening data ( n= 5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n =3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results: A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n =360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion: An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Background: Hepatic cystic echinococcosis (CE) is an infectious zoonotic parasitic disease, and the insidious onset and slow progression of hepatic CE usually contributes to delayed diagnosis and treatment. Hepatocellular carcinoma (HCC) is the fourth most common malignant tumor. Co-existence of CE and HCC is fairly rare in clinical settings and the association between the two is still not well recognized. We report a case of hepatic CE complicated with HCC which are radically resected and raise some questions worth thinking about., Case Summary: A 70-year-old man presented with upper abdominal pain. On admission, laboratory data showed that, except for hepatitis B surface antigen positivity, other indicators were normal, including alpha-fetoprotein. Computed tomography of the abdomen revealed a huge polycystic lesion in left liver lobe, without reinforcement after enhanced scanning and sized about 16.9 cm × 12.2 cm, which was considered a type II hydatid cyst. Multiple small solid lesions were also found adjacent to it, and thus it was highly suspected as a malignant tumor. After a multidisciplinary team discussion, the diagnosis of co-occurrence of hepatic CE and HCC was made. According to Romic classification, the case belongs to type IIb, and radical left hemi-hepatectomy was performed. Postoperative pathological examination revealed CE co-existence with well-differentiated HCC, consistent with the preoperative diagnosis., Conclusion: With the combination of hepatitis B and obvious extrusion by large hydatid, the HCC risk of a patient might be higher., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

In ophthalmologic or otolaryngologic studies, bilateral correlated data often arise when observations involving paired organs (e.g., eyes, ears) are measured from each subject. Based on Donner's model , in this paper, we focus on investigating the relationship between the disease probability and covariates (such as ages, weights, gender, and so on) via the logistic regression for the analysis of bilateral correlated data. We first propose a new minorization-maximization (MM) algorithm and a fast quadratic lower bound (QLB) algorithm to calculate the maximum likelihood estimates of the vector of regression coefficients, and then develop three large-sample tests (i.e., the likelihood ratio test, Wald test, and score test) to test if covariates have a significant impact on the disease probability. Simulation studies are conducted to evaluate the performance of the proposed fast QLB algorithm and three testing methods. A real ophthalmologic data set in Iran is used to illustrate the proposed methods.

The Poisson item count technique (PICT) is a survey method that was recently developed to elicit respondents' truthful answers to sensitive questions. It simplifies the well-known item count technique (ICT) by replacing a list of independent innocuous questions in known proportions with a single innocuous counting question. However, ICT and PICT both rely on the strong "no design effect assumption" (ie, respondents give the same answers to the innocuous items regardless of the absence or presence of the sensitive item in the list) and "no liar" (ie, all respondents give truthful answers) assumptions. To address the problem of self-protective behavior and provide more reliable analyses, we introduced a noncompliance parameter into the existing PICT. Based on the survey design of PICT, we considered more practical model assumptions and developed the corresponding statistical inferences. Simulation studies were conducted to evaluate the performance of our method. Finally, a real example of automobile insurance fraud was used to demonstrate our method., (© 2020 John Wiley & Sons Ltd.)

Biomarker selection has played an increasingly important part in modern medicine with advances of omics techniques. Kohonen self-organizing map is a well-established variable reduction algorithm in identifying significant biomarkers based on variable clustering. However, high dimensionality but small sample size of omics data makes self-organizing map-based model problematic in terms of selection stability and reproducibility. A novel feature screening system is presented in this study by coupling bootstrap with synergy self-organizing map-based orthogonal partial least squares discriminant analysis for stable and biologically meaningful metabolic biomarker selection. In the proposed feature screening system, particle swarm optimization algorithm is utilized to configure synergy self-organizing map-based orthogonal partial least squares discriminant analysis to perform the combination of clusters in a heuristic learning manner, enabling flexible selection of more informative features cost-effectively. Based on the paradigm of ensemble feature selection, bootstrap is adopted to explore significant variables consistently identified across multiple feature selectors rather than a single one. The feasibility of the novel feature screening system is evaluated by two most common inherited metabolic diseases, methylmalonic academia and propionic academia, using urinary metabolomics data. With the desirable classification performance, the proposed feature screening system outperforms simpler techniques in the identification of more features closely correlated with the metabolic mechanisms and the stability of selected candidate biomarkers against sample variations. Besides, the novel feature screening system greatly degrades the sensitivity of identified candidate biomarkers to the network size of self-organizing map, benefiting the identification of a suitable and stable final candidate biomarker list., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In some medical researches such as ophthalmological, orthopaedic and otolaryngologic studies, it is often of interest to compare multiple groups with a control using data collected from paired organs of patients. The major difficulty in performing the data analysis is to adjust the multiplicity between the comparison of multiple groups, and the correlation within the same patient's paired organs. In this article, we construct asymptotic simultaneous confidence intervals (SCIs) for many-to-one comparisons of proportion differences adjusting for multiplicity and the correlation. The coverage probabilities and widths of the proposed CIs are evaluated by Monte Carlo simulation studies. The methods are illustrated by a real data example., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 Informa UK Limited, trading as Taylor & Francis Group.)

The article "MicroRNA-29 targets FGF2 and inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway, by M. Xu, G.-L. Tian, C.-C. Hao, M. Shi, D.-J. Zha, K. Liang, published in Eur Rev Med Pharmacol Sci 2019; 23 (12): 5215-5222. DOI: 10.26355/eurrev&#95;201906&#95;18186. PMID: 31298371" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18186.

Background: Elevated blood C24:0- and C26:0-carnitines and lysophosphatidylcholines (LPCs) were reported as diagnostic biomarkers for X-linked adrenoleukodystrophy (X-ALD). Our aim was to establish the reference intervals of very long-chain (VLC) acylcarnitines (C20-C26) and LPCs in Chinese population, and evaluate valuable biomarkers and develop panel for screening X-ALD in China., Methods: The method of FIA-MS/MS-based quantification of VLC acylcarnitines and LPCs was validated in order to determine their concentrations in dried blood spots from 7 X-ALD boys, 396 age-matched healthy controls, and 3078 putative normal newborns. Screening performance of these metabolites for X-ALD was clinically evaluated., Results: The reference intervals of VLC acylcarnitines, LPCs and their ratios were established in Chinese population, and for some metabolites like C26 and C26:0-LPC, the reference intervals were found to be significantly different between children and newborns. C24 and C26, C26:0-LPC, C24/C22 and C26/C22 ratios were found to have better performance than other analytes to identify X-ALD boys from normal children., Conclusion: C26:0-LPC, C24 and C26 are three most valuable biomarkers for screening of X-ALD in children group. The information of age-related variations in concentration of some biomarkers is helpful for accurate screening of X-ALD., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recently, although advances were made on modeling multivariate count data, existing models really has several limitations: (i) The multivariate Poisson log-normal model (Aitchison and Ho, 1989) cannot be used to fit multivariate count data with excess zero-vectors; (ii) The multivariate zero-inflated Poisson (ZIP) distribution (Li et al., 1999) cannot be used to model zero-truncated/deflated count data and it is difficult to apply to high-dimensional cases; (iii) The Type I multivariate zero-adjusted Poisson (ZAP) distribution (Tian et al., 2017) could only model multivariate count data with a special correlation structure for random components that are all positive or negative. In this paper, we first introduce a new multivariate ZAP distribution, based on a multivariate Poisson distribution, which allows the correlations between components with a more flexible dependency structure, that is some of the correlation coefficients could be positive while others could be negative. We then develop its important distributional properties, and provide efficient statistical inference methods for multivariate ZAP model with or without covariates. Two real data examples in biomedicine are used to illustrate the proposed methods., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bilateral correlated data are often encountered in medical researches such as ophthalmologic (or otolaryngologic) studies, in which each unit contributes information from paired organs to the data analysis, and the measurements from such paired organs are generally highly correlated. Various statistical methods have been developed to tackle intra-class correlation on bilateral correlated data analysis. In practice, it is very important to adjust the effect of confounder on statistical inferences, since either ignoring the intra-class correlation or confounding effect may lead to biased results. In this article, we propose three approaches for testing common risk difference for stratified bilateral correlated data under the assumption of equal correlation. Five confidence intervals of common difference of two proportions are derived. The performance of the proposed test methods and confidence interval estimations is evaluated by Monte Carlo simulations. The simulation results show that the score test statistic outperforms other statistics in the sense that the former has robust type I error rates with high powers. The score confidence interval induced from the score test statistic performs satisfactorily in terms of coverage probabilities with reasonable interval widths. A real data set from an otolaryngologic study is used to illustrate the proposed methodologies.

Objective: Studies have indicated that miRNAs may prove essential therapeutic targets for the treatment of cancer. The study was designed to investigate the role and therapeutic potential of miR-29 in nasopharyngeal cancer., Materials and Methods: The quantitative Real-time polymerase chain reaction (qRT-PCR) was used for expression analysis. WST-1 assay was used for cell viability assessment. The 4',6-diamidino-2-phenylindole (DAPI) staining and electron microscopic analysis was used for the detection of apoptosis and autophagy, respectively. Transwell assays were used for cell migration and invasion assay., Results: It was found that miR-29 is significantly downregulated in nasopharyngeal cancer cell lines. Overexpression of miR-29 causes decrease in the viability of CNE2 nasopharyngeal cancer cells via induction of apoptosis and autophagy. Bioinformatics analysis indicated FGF2 to be the target of miR-29 in CNE2 cells, which was also confirmed by luciferase reporter assay. The qRT-PCR results showed fibroblast growth factor 2 (FGF2) to be significantly upregulated in the nasopharyngeal cancer cell lines. However, miR-29 overexpression in CNE2 cells resulted in post-transcriptional suppression of FGF2 expression. Nonetheless, silencing of FGF2 also caused inhibition of CNE2 cell proliferation via induction of apoptosis and autophagy. Overexpression of FGF2 could reverse the effects of miR-29 overexpression on the proliferation of CNE2 cells. Moreover, overexpression of miR-29 causes significant decline in the phosphorylation of PI3K and AKT expression cells and inhibits their migration and invasion of the CNE2 cells. Finally, miR-29 overexpression could also suppress the subcutaneous xenografted tumor growth., Conclusions: The findings of the present study indicate the therapeutic implications of miR-29 in nasopharyngeal carcinoma.

Thermal management materials (TMMs) used in electronic devices are crucial for future electronics and technologies such as flexible electronics and artificial intelligence (AI) technologies. As future electronics will work in a more complicated circumstance, the overheating and overcooling problems can exist in the same electronics while the common TMMs cannot meet the demand of thermal management for future electronics. In this work, nacre-mimetic graphene-based films with super flexibility and durability (in over 10,000 tensile cycles), excellent capability to dissipate excess heat (20.84 W/(m·K) at only 16-22 μm thickness), and outstanding heating performance to generate urgent heat for electronics under extremely cold conditions are fabricated by a facile solution casting method, and the fabricated composites are proved to be superior multifunctional TMMs for the thermal management in electronic chips. In addition, the application of the paper-like films with high in-plane thermal conductivity to a flexible heat spreader and film heater is demonstrated by simulation using a finite volume method, which shows the high importance of the in-plane thermal conductivity in thermal management of electronics.

In a parallel group study comparing a new treatment with a standard of care, missing data often occur for various reasons. When the outcome is binary, the data from such studies can be summarized into a 2 × 3 contingency table, with the missing observations in the last column. When the missingness is neither related to the outcome of interest nor related to other outcomes from the study but it is covariate dependent with the sole covariate being treatment, this type of missing data mechanism is considered as missing at random. In 2016, Tian et al.  proposed three statistics to test the hypothesis that the response rate is equivalent for a parallel group study with missing data. The asymptotic limiting distributions of these test statistics were used for statistical inference. However, asymptotic approaches for testing proportions generally do not have satisfactory performance with regard to type I error rate control for a clinical trial with the sample size from small to medium. For this reason, we consider an exact approach based on maximization to provide valid and efficient statistical inference for a parallel group study with missing data. Exact approaches can guarantee the type I error rate and they are computationally feasible in this setting. We conduct extensive numerical studies to compare the performance of the exact approach based on the three statistics for a one-sided hypothesis testing problem. We conclude that the exact approach based on the likelihood ratio statistic is more powerful than the exact approach based on the other two statistics. Two real clinical trial data sets are used to illustrate the application of the proposed exact approach.

In stratified bilateral studies, responses from two paired body parts are correlated. Confidence intervals (CIs), which reveal various features of the data, should take the correlations into account. In this article, five CI methods (sample-size weighted naïve Maximum likelihood estimation (MLE)-based Wald-type CI, complete MLE-based Wald-type CI, profile likelihood CI, MLE-based score CI and pooled MLE-based Wald-type CI) are derived for proportion ratios under the assumption of equal correlation coefficient within each stratum. Monte Carlo simulation shows that the complete MLE-based Wald-type CI approach generally produces the shortest mean interval width and satisfactory empirical coverage probability with close form solution; while the profile likelihood CI and the MLE-based score CI provide preferred ratio of non coverage probability and are more symmetric. Two real examples are used to demonstrate the performance of the proposed methods.

To analyze univariate truncated normal data, in this paper, we stochastically represent the normal random variable as a mixture of a truncated normal random variable and its complementary random variable. This stochastic representation is a new idea and it is the first time to appear in literature. According to this stochastic representation, we derive important distributional properties for the truncated normal distribution and develop two new expectation-maximization algorithms to calculate the maximum likelihood estimates of parameters of interest for Type I data (without and with covariates) and Type II/III data. Bootstrap confidence intervals of parameters for small sample sizes are provided. To evaluate the performance of the proposed methods for the truncated normal distribution, in simulation studies, we first focus on the comparison of estimation results between including the unobserved data counts and excluding the unobserved data counts, and we next investigate the impact of the number of unobserved data on the estimation results. The plasma ferritin concentration data collected by Australian Institute of Sport and the blood fat content data are used to illustrate the proposed methods and to compare the truncated normal distribution with the half normal, the folded normal, and the folded normal slash distributions based on Akaike information criterion and Bayesian information criterion.

Objective: To systematically investigate PIK3CA mutations in isolated macrodactyly. Methods: Overgrowth tissues from 12 isolated macrodactyly patients who were treated at Department of Hand Surgery, Beijing Jishuitan Hospital from May to August 2017 were collected during operation.There were 6 male and 6 female patients with average age of 4.5 years. DNA was tested for PIK3CA mutation using a targeted Sanger DNA sequencing method.Samples with negative Sanger result were tested with a next generation DNA sequencing(NGS)panel targeting 47 cancer hotspot genes including PIK3CA. Results: By targeted Sanger sequencing, PIK3CA mutations were detected in 9 of the 12 patients, with mutation level ranging from 7% to 27%.The PIK3CA mutations observed were p. His1047Arg, p.His1047Leu, p.Glu545Lys, and p. Glu542Lys.NGS found p. Glu453Lys in one additional patient, allowing the total positive rate to 10/12.All PIK3CA mutations detected in the study were cancer hotspot mutations.Among all tissue types tested, adipose tissue had the highest mutation detection rate(9/9), followed by nerve(10/12) and skin(10/12). Conclusions: A high proportion of isolated macrodactyly patients carry a PIK3CA mutation.Adipose, nerve, and skin are ideal tissue resources for PIK3CA mutation detection.Targeted Sanger sequencing with reflex to NGS represents a cost-effective strategy to test PIK3CA mutations in isolated macrodactyly.

The main objective of this paper is to derive the valid sampling distribution of the observed counts in a case-control study with missing data under the assumption of missing at random by employing the conditional sampling method and the mechanism augmentation method. The proposed sampling distribution, called the case-control sampling distribution, can be used to calculate the standard errors of the maximum likelihood estimates of parameters via the Fisher information matrix and to generate independent samples for constructing small-sample bootstrap confidence intervals. Theoretical comparisons of the new case-control sampling distribution with two existing sampling distributions exhibit a large difference. Simulations are conducted to investigate the influence of the three different sampling distributions on statistical inferences. One finding is that the conclusion by the Wald test for testing independency under the two existing sampling distributions could be completely different (even contradictory) from the Wald test for testing the equality of the success probabilities in control/case groups under the proposed distribution. A real cervical cancer data set is used to illustrate the proposed statistical methods.

Background: Root avulsion to all 5 roots of the brachial plexus is a common presentation and keeps a major reconstructive challenge. The contralateral C7 (CC7) nerve transfer has been used in treating brachial plexus avulsion injury (BPAI) since 1986. However, the effectiveness of the procedure remains a subject of controversy. The aim of this meta-analysis was to study surgical outcomes regarding motor and sensory recovery after CC7 nerve transfer., Methods: Chinese or English (i.e., "contralateral c-7", "contralateral c7", "c7 nerve root", and "seventh cervical nerve root") keywords were used for a literature search for articles related to CC7 nerve transfer in several databases (i.e., PubMed, Cochrane, Embase, CNKI, CQVIP, and Wanfang Data). Clinical research articles were screened, and animal studies as well as duplicate publications were excluded. Muscle strength and sensory recovery were considered to be effective only when the scores on the United Kingdom Medical Research Council scale were equal to or higher than M3 and S3, respectively., Results: The overall ipsilateral recipient nerve recovery rates were as follows: the efficiency rate for muscle strength recovery after CC7 nerve transfer was 0.57 (95% confidence interval [CI]: 0.48-0.66) and for sensory recovery was 0.52 (95% CI: 0.46-0.58). When the recipient nerve was the median nerve, the efficiency rate for muscle strength recovery was 0.50 (95% CI: 0.39-0.61) and for sensory was 0.56 (95% CI: 0.50-0.63). When the recipient nerve was the musculocutaneous nerve and the radial nerve, the efficiency rate for muscle strength recovery was 0.74 (95% CI: 0.65-0.82) and 0.50 (95% CI: 0.31-0.70), respectively., Conclusions: Transfer of CC7 nerves to musculocutaneous nerves leads to the best results. CC7 is a reliable donor nerve, which can be safely used for upper limb function reconstruction, especially for entirely BPAI. When modifying procedures, musculocutaneous nerves and median nerve can be combined as recipient nerves.

The key to successful treatment of perilunate injuries is to achieve early anatomic reduction and maintain the carpal alignment. Open surgery may lead to capsular scarring and joint stiffness. Furthermore, there is increased chance of damage of the already tenuous blood supply to scaphoid and the torn ligaments. Recently, arthroscopic-assisted management of perilunate injuries has been suggested. This article describes the surgical technique and outcome of this minimally invasive approach for perilunate injuries., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Powdery mildew (PM) of cucumber (Cucumis sativus), caused by Podosphaera xanthii, is a major foliar disease worldwide and resistance is one of the main objectives in cucumber breeding programs. The resistance to PM in cucumber stem is important to the resistance for the whole plant. In this study, genetic analysis and gene mapping were implemented with cucumber inbred lines NCG-122 (with resistance to PM in the stem) and NCG-121 (with susceptibility in the stem). Genetic analysis showed that resistance to PM in the stem of NCG-122 was qualitative and controlled by a single-recessive nuclear gene (pm-s). Susceptibility was dominant to resistance. In the initial genetic mapping of the pm-s gene, 10 SSR markers were discovered to be linked to pm-s, which was mapped to chromosome 5 (Chr.5) of cucumber. The pm-s gene's closest flanking markers were SSR20486 and SSR06184/SSR13237 with genetic distances of 0.9 and 1.8 cM, respectively. One hundred and fifty-seven pairs of new SSR primers were exploited by the sequence information in the initial mapping region of pm-s. The analysis on the F 2 mapping population using the new molecular markers showed that 17 SSR markers were confirmed to be linked to the pm-s gene. The two closest flanking markers, pmSSR27and pmSSR17, were 0.1 and 0.7 cM from pm-s, respectively, confirming the location of this gene on Chr.5. The physical length of the genomic region containing pm-s was 135.7 kb harboring 21 predicted genes. Among these genes, the gene Csa5G623470 annotated as encoding Mlo-related protein was defined as the most probable candidate gene for the pm-s. The results of this study will provide a basis for marker-assisted selection, and make the benefit for the cloning of the resistance gene.

Some existing confidence interval methods and hypothesis testing methods in the analysis of a contingency table with incomplete observations in both margins entirely depend on an underlying assumption that the sampling distribution of the observed counts is a product of independent multinomial/binomial distributions for complete and incomplete counts. However, it can be shown that this independency assumption is incorrect and can result in unreliable conclusions because of the under-estimation of the uncertainty. Therefore, the first objective of this paper is to derive the valid joint sampling distribution of the observed counts in a contingency table with incomplete observations in both margins. The second objective is to provide a new framework for analyzing incomplete contingency tables based on the derived joint sampling distribution of the observed counts by developing a Fisher scoring algorithm to calculate maximum likelihood estimates of parameters of interest, the bootstrap confidence interval methods, and the bootstrap testing hypothesis methods. We compare the differences between the valid sampling distribution and the sampling distribution under the independency assumption. Simulation studies showed that average/expected confidence-interval widths of parameters based on the sampling distribution under the independency assumption are shorter than those based on the new sampling distribution, yielding unrealistic results. A real data set is analyzed to illustrate the application of the new sampling distribution for incomplete contingency tables and the analysis results again confirm the conclusions obtained from the simulation studies.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency., Methods: The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard., Results: G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 μmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 μmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P < 0.001 for DBS samples plus sodium citrate that were examined the first day after preparation, there were no significant differences in the mean GSH concentration and GSH/GSSG ratio between the G6PD deficiency-positive and negative groups when examined three days after sample preparation., Conclusion: The concentration of GSH and the ratio of GSH/GSSG in blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

Objective: To explore the correlation between effect of PIO (pioglitazone, PIO) on learning as well as memory and ERK1/2 (extracellular signal regulated kinase 1/2, ERK1/2) pathway in T2DM (type 2 diabetes mellitus, T2DM) rats, further to elucidate the potential mechanism of PIO in improvement of learning and memory., Methods: 12-week-old male SD rats (number of 10 per group) were randomly divided into control group (CON), T2DM group (DM) and T2DM +PIO group (DM+PG). Rats in DM and DM+PG groups were given high fat diet for 20 weeks, then treated with Streptozotocin (27mg/kg) by intraperitoneal injection at 21week. After 72h, the FBG (fasting blood glucose, FBG) was greater than 7.0mmol/L can considered T2DM rats. DM+PG group was treated with PIO (10 mg·kg -1 ·d -1 ) by gavage daily. After Hyperinsulinemic-Euglycemic Clamp Study and Morris water maze test at 30-week, all of animals were sacrificed. The expressions of RKIP (Raf-1 kinase inhibitor protein, RKIP) and ERK1/2 in hippocampus were detected using Western Blot and real-time PCR., Results: The FBG level: DM group (7.68±0.54mmol/L) was higher than CON group (5.35±0.63mmol/L) and DM+PG group (6.07±0.84mmol/L), the differences were considered statistically significant (P <0.05). Hyperinsulinemic-Euglycemic Clamp Studies: GIR (glucose infusion rate, GIR) of DM group (21.02±5.10 mg·kg -1 ·d -1 ) was less than CON group (27.64±3.87 mg·kg -1 ·d -1 ) and DM+PG group (26.04 ±5.41 mg·kg -1 ·d -1 ), the differences were considered statistically significant (P <0.05). Morris water maze training: The escape latencies and searching platform performance of DM group (24.54±5.02s) decreased significantly compared with CON group (16.73±4.02s) and DM+PG group (18.05±4.12s) (P <0.05). Changes of RKIP, ERK, p-ERK protein relative content in rat hippocampus: Compared with CON groupand DM+PG group, the relative content of RKIP in DM group remarkably increased (P<0.01); ERK protein levels were not considered statistically significant among the three groups (P>0.05); The relative content of p-ERK1/2 protein in CON group and DM+PG group rats dorsal were higher than those in group DM, the difference was considered statistically significant (P<0.01). Changes in hippocampus of rat RKIP and ERK gene relative content: Compared with CON group and DM+PG group, levels of RKIP mRNA in DM group were significantly increased (P<0.01); ERK mRNA levels were not considered statistically significant among the three groups (P>0.05)., Conclusion: Activation of ERK1/2 signal transduction pathway via reducing RKIP in the hippocampus may be one of the mechanisms of PIO to improve the learning and memory of the T2DM rats., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Although the item count technique is useful in surveys with sensitive questions, privacy of those respondents who possess the sensitive characteristic of interest may not be well protected due to a defect in its original design. In this article, we propose two new survey designs (namely the Poisson item count technique and negative binomial item count technique) which replace several independent Bernoulli random variables required by the original item count technique with a single Poisson or negative binomial random variable, respectively. The proposed models not only provide closed form variance estimate and confidence interval within [0, 1] for the sensitive proportion, but also simplify the survey design of the original item count technique. Most importantly, the new designs do not leak respondents' privacy. Empirical results show that the proposed techniques perform satisfactorily in the sense that it yields accurate parameter estimate and confidence interval.

As the skeleton substances of lignocellulosic biomass cell wall and the precursor of biofuels production, the research on cellulose structure, an important natural biomarcromolecules, attracts great attention. Considering its in situ features and higher resolution, Raman spectroscopy has been used to investigate the structure of cellulose molecular chain and cellulose aggregation structure at multi-scale. In this paper, the configurations and corresponding parameters of two types of Raman spectroscopy (Dispersive Raman and FT-Raman) were compared. Subsequently, the utilization of Raman spectroscopy in cellulose micro-distribution, cellulose enzyme hydrolysis, cellulose chain orientation and deformation, cellulose crystallinity and polymorphic transformation was discussed in detail. Given the existing deficiencies of the Raman spectroscopy when used to investigate the natural cellulose, some suggestions were proposed in order to promote the application of Raman spectroscopy to the research of natural macromolecular.

Density, which is closely relate with many physical and mechanical properties of bamboo, is one of the important indicators of bamboo material properties. Moreover, because of existing different moisture gradients in bamboo, the measured results of the density are different. Based on X-ray computed tomography (X-CT) technology, the divergent degree of the CT values of 7 different aged Moso bamboo was compared under oven-dried, air-dried and water-saturated conditions. Except for the 4-year-old and 10-year-old Moso bamboo, the CT values of other aged bamboos have minor differences with each other; the models for the measured CT values and the corresponding densities of Moso bamboo were respectively fitted under oven-dried, air-dried and water-saturated conditions. Meanwhile, the model was also fitted under different moisture gradients, which was composed by the measured CT values and the corresponding densities of Moso bamboo. Then the relations between the CT values andthe densitiesof 7 different aged Moso bamboo were systematically analyzed under single moisture content and three moisture gradients;the CT values were fitted under oven-dried condition, of which the radial positions are relative to the outer of Moso bamboo. According to the relation between the CT value and the density, the fitting curves explain the reasons for the radial density variations of 7 different aged Moso bamboo. Results show that the relations, which are fitted by the measured densities and the corresponding CT values of 7 different aged Moso bamboo under oven-dried, air-dried and water-saturated conditions, are good linear and the slopes of those models are approximate; the relation of the densities with the CT values for Moso bamboo is linear under different moisture gradients, moreover, which is rarely affected by moisture. The regression equation is: D=0.001 H+1.003 2, R2=0.968 3(D is the density, H is the CT value) and the determination coefficient of the validation model is: R2=0.974 3; there is no obvious variation between the densities of the inner and the outer, but not in middle part to 7 different aged Moso bamboo under oven-dried condition. To realize rapid detection on the densities of Moso bamboo under different moisture content, these results provide technical support and data reference. At the same time, X-ray computed tomography (X-CT) technology also puts forward a new feasible way for the further studies of bamboo material properties and structure.

Purpose The aim of this article is to differentiate neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) from biliary atresia (BA) by total hexose. Methods A total of 11 patients with NICCD, 29 patients with BA, and 4,898 children as controls were involved in this study. The blood concentration of amino acids, carnitine, acylcarnitines, and total hexose were measured in dry blood spots (DBS) using tandem mass spectrometry (MS/MS). Results In the patients with NICCD, the blood concentration of the total hexose (15.3 ± 9.0 mmol/L vs. 7.3 ± 2.7 mmol/L; p < 0.001), citrulline (Cit) (197.9 ± 93.7 µmol/L vs. 17.5 ± 7.4 µmol/L; p < 0.001) were higher than those of patients with BA. Using total hexose (> 10 mmol/L), Cit (> 55 µmol/L) to diagnose NICCD, the sensitivity and specificity were 66.7 and 97.8% and 90.0 and 99.1%, respectively, and all of the areas under the receiver-operating characteristic curves were greater than 0.85. Conclusion Elevated total hexose in DBS measured by MS/MS associated with elevated amino acids, especially Cit can be used to diagnose NICCD and differentiate it from BA., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To evaluate the outcomes of lesser arc perilunate injuries (Perilunate dislocations) treated with arthroscopically assisted mini-invasive reduction and fixation., Methods: Between 2012 and 2014, 5 patients who had a perilunate dislocation were treated with arthroscopically assisted reduction and percutaneous fixation. The mean follow-up was 17.8 months (range, 10 to 32 months). Clinical outcomes were evaluated on the basis of range of motion; grip strength; Mayo wrist score; Quick disabilities of the arm, shoulder and hand questionnaire; and patient-rated wrist evaluation score. Radiographic evaluations included carpal alignments and any development of arthritis., Results: The range of flexion-extension motion of injured wrist averaged 84% of the values for contralateral wrist. The grip strength of the injured wrist averaged 90% of the values for the contralateral wrists. The mean Quick Disabilities of the arm, shoulder and hand score was 1, and the mean Patient-Rated Wrist Evaluation score was 5. According to the Mayo wrist scores, the overall functional outcomes were rated as excellent in all the patients. Reduction obtained during the operation was maintained within normal ranges in all the patients. Arthritis had not developed in any patient at the end of the follow-up., Conclusion: Arthroscopic mini-invasive reduction with percutaneous fixation is a reliable and favorable alternative in the treatment of perilunate dislocations according to our early results.

Objective: To investigate the outcomes of applying microvascular anastomotic coupling devices in solitary upper extremity artery injury repairs and to optimize parameters for optimal clinical outcome., Methods: From March to September 2013, 19 injured arteries from 18 male patients who presented at Department of Hand Surgery, Beijing Jishuitan Hospital with traumatic arterial lacerations of their upper extremities went through rapid repair procedures. COUPLER, a microvascular anastomotic coupling device was applied in these artery injury repair operations. The 19 repaired arteries included 3 brachial arteries, 6 ulnar arteries and 10 radial arteries. After the procedures, all the 18 patients were then followed up by clinical specialists and examined with color doppler flow imaging for the effective recovery of artery circulation and upper extremities functionality., Results: The average time of artery repairs for all the 19 damaged arteries among the 18 patients was 278 s and the average follow-up time was (71.5±40.9) d with the longest follow-up time as 116 d and shortest as 14 d. No patient returned to the operating room after the procedures and after being dismissed from the hospital. None of the 18 cases were reported to have problems with circulation and thrombosis formation in their upper extremities. Color Doppler imaging showed that the arterial anastomotic site for all the 19 repaired arteries were unobstructed with artery blood spectrum at both ends. Three patients with radial artery repairs complained about mild pressure pain at the site of vascular anastomosis; while the other 15 patients all expressed satisfactory outcomes of the surgery and recovery. These evidences indicated that the outcomes of our initial evaluation for the solitary upper extremity artery injury repairs by using anastomotic coupling devices were positive., Conclusion: Our observations have showed that microvascular anastomotic coupling devices can be used for repairing of solitary upper extremity artery injures. The procedures are quick, effective and safe. The clinical application of this microvascular anastomotic coupling device in artery injures is promising, however, additional evidences through further clinical investigation with more cases are warranted.

The wood property and production process affect quality of Guqin. At the same time, Guqin shape with cavity layout relations to the improvement of Guqin technology and inheritance, so it's very important to get the internal cavity characteristics and parameters on the condition of non-destructive the structure of Guqin. The image of interior structure in Guqin was investigated by overall scanning based on non-destructive testing technology of computed tomography, which texture of faceplate, connection method between faceplate and soleplate and interior defects were studied. The three-dimensional reconstruction of Guqin cavity was achieved through Mimics software of surface rendering method and put the two-dimensional CT tomography images convert into three-dimensional, which more complete show interior structural form in Guqin, and finally the parameter of cavity dimensions was obtained. Experimental research shows that there is significant difference in Guqin interior structure between Zhong-ni and Luo-xia type, in which the fluctuation of the interior surfacein Zhong-ni type's is larger than that in Luo-xia type; the interior volume of Zhong-ni typeis less than that of Luo-xia type, especially in Guqin neck. The accurate internal information of Guqin obtained through the computed tomography (CT) technology will provide technical support for the Guqin manufacture craft and the quality examination, as well as provide the reference in the aspect of non-destructive testing for other traditional precious internal structure research.

Motion capture is attracting more and more attention due to its potential wide applications in various fields. However, traditional methods for motion capture still have weakness such as high cost and space consuming. Based on these considerations, a flexible, highly stretchable strain sensor with high gauge factor for motion capture is fabricated with carbon nanotube (CNT) array double helices as the main building block. Ascribed to the unique flexible double helical CNT-array matrix, the strain sensor is able to measure strain up to 410%, with low hysteresis. Moreover, a demonstration of using this strain sensor for capture hand motion and to control a mechanical hand in real time is also achieved. A model based on finite difference method is also made to help understand the mechanism of the strain sensors. Our work demonstrates that strain sensors can measure very large strain while maintaining high sensitivity, and the motion capture based on this strain sensor is expected to be less expensive, more convenient and accessible.

The aim of the present meta-analysis was to investigate the correlation of promoter methylation of the p16 and Ras association domain family 1 isoform A (RASSF1A) genes with the risk of the development of papillary thyroid cancer (PTC). A number of electronic databases were searched without language restrictions as follows: Medline (1966-2013), the Cochrane Library database (Issue 12, 2013), Embase (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013). A meta-analysis was performed with the use of Stata statistical software. The odds ratios (ORs), ratio differences (RDs) and 95% confidence intervals (95% CIs) were calculated. In the present meta-analysis, eleven clinical cohort studies with a total of 734 patients with PTC were included. The results of the current meta-analysis indicated that the frequency of promoter methylation of p16 in cancer tissues was significantly higher compared with that in normal, adjacent and benign tissues (cancer tissues vs. normal tissues: OR=7.14; 95% CI, 3.30-15.47; P<0.001; cancer tissues vs. adjacent tissues: OR=11.90; 95% CI, 5.55-25.52; P<0.001; cancer tissues vs. benign tissues: OR=2.25; 95% CI, 1.67-3.03; P<0.001, respectively). The results also suggest that RASSF1A promoter methylation may be implicated in the pathogenesis of PTC (cancer tissues vs. normal tissues: RD=0.53; 95% CI, 0.42-0.64; P<0.001; cancer tissues vs. adjacent tissues: RD=0.39; 95% CI, 0.31-0.48; P<0.001; cancer tissues vs. benign tissues: RD=0.39; 95% CI, 0.31-0.47; P<0.001; respectively). Thus, the present meta-analysis indicates that aberrant promoter methylation of p16 and RASSF1A genes may play a crucial role in the pathogenesis of PTC.

Nanometer-sized hydroxide active centers are uniformly and strongly hybridized into a graphene framework by means of defect-anchored nucleation and spatially confined growth, resulting in a superior electrocatalyst for oxygen evolution reaction. This family of strongly coupled complexes and the topology-assisted fabrication strategy is expected to open up new avenues of research. It sheds light on a novel branch of advanced nano-architectured materials., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A hydroxide/graphene hybrid electrocatalyst for oxygen evolution reaction is proposed by Q. Zhang and co-workers, as described on page 4516. Nanosized hydroxide active centers are uniformly and strongly hybridized into a nitrogen-doped graphene framework via defect-anchored nucleation and spatially confined growth. The as-obtained hydroxide/graphene is demonstrated to overperform commercial Ir/C catalysts and compete favorably against reported alternatives for high-performance oxygen evolution reactivity., (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)