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Background: An early trend in the mean age of pubertal onset appears in adolescents, but the association between body fat percentage (BF%) of children and precocious puberty is unclear. The aim of ...

Objectives In this study, we evaluated the concordance between the ultrasonographic stage of breast (US B) and Tanner stage of breast (TS B) for overweight and obese girls based on a school population study. Methods We conducted multistage, stratified cluster, and random-proportional sampling and ultimately included 221 girls (aged 6–10 years). Results This study revealed that the concordance was poor (accuracy=0.19 (95% confidence interval: 0.14, 0.25)) between US B and TS B among the 221 participants. When our subjects were stratified by weight, we observed a weak association between US B and TS B in the thin/normal weight group (r=0.34, p=0.001) but not in the overweight (r=0.097, p=0.38) or obese groups (r=–0.19, p=0.206), and as the body mass index (BMI) z-score increased, the overestimation ratio of TS B increased. US B manifested a positive correlation with breast bud diameter (BD) (r=0.885, p Conclusions As the BMI z-score increased, the correlation between the two methods declined, and the overestimation ratio of TS B increased. US B is an objective and quantitative method used to evaluate breast development, and whether BD might replace US B as a routine diagnostic method to evaluate breast development in clinical practice needs to be confirmed in larger-sample studies.

Evaluation of hospital quality is of great significance for the promotion of the development of medical care. Hospital standardized mortality ratio (HSMR) is the ratio of hospital observed mortalit...

To investigate the prevalence of precocious puberty in school-based population in Zhongshan, Guangdong, China. We recruited a total of 4058 students in grades 1–3 using a multistage stratified cluster random sampling method in a population-based cross-sectional study. We evaluated height, weight, and development of breast and pubic hair in girls, breast development was evaluated by inspection and palpation combined with ultrasound detection for overweight and obese girls, and testicular volume and development of pubic hair in boys. We estimated overall, sex-, age, and district-specific prevalence of precocious puberty and examined the association between prevalence of precocious puberty and body mass index (BMI). The unadjusted and adjusted prevalence of precocious puberty by Tanner stage was 4.74% (girls:8.78%, boys:2.58%) and 6.19% (girls:11.47%, boys:3.26%), respectively. In both urban and suburban areas, the prevalence of precocious puberty was higher in the overweight and obese group than in the normal-weight group (p

A series of Tb-based metal–organic frameworks (Tb-MOFs) were successfully synthesized by a solvothermal method. The size and morphology of the as-obtained Tb-MOFs can be effectively controlled via regulating the experimental conditions such as the volume fraction of DMF and the molar ratio of Tb3+ to NaOH. It is found that all the samples exhibit strong green emissions under ultraviolet excitation, corresponding to 5D4 → 7FJ transitions of Tb3+. Interestingly, Tb-MOFs displayed an efficient and distinct luminescence quenching by Cu2+ in aqueous solutions. The competitive fluorescence detection experiments indicate that these Tb-MOFs sensors can be used as a high selective and sensitive sensor of Cu2+ detection with the detection limit of 10 µmol·L−1, which can be used as a promising fluorescence sensor for Cu2+ detection in daily life.

Summary In vitro spermatogenesis has been achieved by culturing mouse embryonic stem cells (ESCs) together with a cell suspension of male juvenile gonad. However, for human fertility treatment or preservation, patient-specific ESCs or juvenile gonad is not available. We therefore aim to achieve in vitro spermatogenesis using male germline stem cells (GSCs) without the use of juvenile gonad. GSCs, when cultured on immortalized Sertoli cells, were able to enter meiosis, reach the meiotic metaphase stages, and sporadically form spermatid-like cells. However, the in vitro-formed pachytene-like spermatocytes did not display full chromosome synapsis and did not form meiotic crossovers. Despite this, the meiotic checkpoints that usually eliminate such cells to prevent genomic instabilities from being transmitted to the offspring were not activated, allowing the cells to proceed to the meiotic metaphase stages. In vitro-generated spermatid-like cells should thus be thoroughly investigated before being considered for clinical use., Graphical Abstract, Highlights • Mouse male germline stem cells were induced to complete meiosis in vitro • Meiotic chromosome synapsis and crossover formation were impaired in vitro • In vitro meiosis appeared sensitive to temperature and Sertoli cell background • Meiosis proceeded faster in vitro and the meiotic M phase often initiated prematurely, In this article, Hamer and colleagues show that, on a feeder layer of Sertoli cells, mouse spermatogonial stem cells can be induced to undergo meiosis in vitro. However, meiotic recombination and checkpoints do not necessarily function properly in vitro, and the authors warn that in vitro-generated spermatid-like cells should be thoroughly analyzed before clinical application can be considered.

Background: Previous studies have shown that postpartum depression negatively affects breastfeeding practices. However, it is not clear whether maternal mood symptoms during pregnancy affect exclusive breastfeeding (EBF) behavior. Our study aimed to quantify the relationship between maternal mood symptoms (depression/anxiety) during pregnancy and EBF.Methods: A cross-sectional study was conducted at Baoan Maternal and Child Health Hospital, Shenzhen, China, from January 1, 2016, to December 31, 2016, among women who had delivered in the hospital and completed the 6-week postpartum visit. A structured questionnaire was designed to collect information on maternal mood symptoms during pregnancy and EBF status at 6 weeks postpartum. Logistic regression models were used to evaluate the associations between maternal mood symptoms (depression/anxiety) during pregnancy and EBF at 6 weeks postpartum.Results: In total, 6324 women were included in this study. In univariate analysis, we observed that depression during pregnancy was associated with a reduced risk for EBF (OR = 0.66; 95% CI: 0.54-0.81; P < 0.001). In the fully adjusted model, depression during pregnancy was still significantly associated with a reduced risk of EBF (OR=0.69; 95% CI: 0.56–0.86; P < 0.001). However, there was no significant difference in the rate of EBF between the anxiety and non-anxiety groups of women (OR=0.88; 95% CI: 0.77–1.01; P > 0.05). Conclusion: We believe that our findings confirm the adverse impact of maternal depression during pregnancy on EBF behavior. Therefore, to improve conditions for breastfeeding of infants, additional attention should be paid to women with depressive symptoms during pregnancy.

Background Nonpharmacological interventions are the first recommendation for cancer-related fatigue, according to current guidelines. There are many forms of nonpharmacological interventions for addressing cancer-related fatigue, but the preferred means remain controversial and are not stated in the guidelines. Therefore, we evaluated the comparative effects and ranks of all major nonpharmacological interventions, according to different assessment methods, in cancer patients with fatigue. Methods Medline, Embase, Cochrane Library, and Allied and Complementary Medicine Database were searched for randomized controlled trials on nonpharmacological treatments for cancer-related fatigue. We assessed the trials' methodological quality using the Cochrane Risk of Bias tool. A Bayesian network meta-analysis and a comparative effects ranking were performed with Aggregate Data Drug Information System software. Results A total of 16,675 items were obtained from the databases, and 182 studies comprising 18,491 participants were included in the analysis. Based on the ranking probabilities, multimodal therapy and qigong ranked best with a Brief Fatigue Inventory; for a Functional Assessment of Cancer Therapy-fatigue scale, combined psychosocial therapies and bright white light therapy ranked best; for the Piper Fatigue Scale, resistance exercise and mindfulness-based stress reduction ranked best; for a multidimensional fatigue inventory, multimodal therapy and cognitive behavioral therapy (CBT) ranked best; for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), acupuncture and CBT ranked best; and for the Profile of Mood States Fatigue Subscale, multimodal therapy, qigong, aerobic exercise, and CBT ranked best. Comprehensive analysis of the results indicated that multimodal therapy, CBT, and qigong might be the optimum selections for reducing cancer-related fatigue. Most of the included studies had low risk of methodological quality problems; however, 59 studies had low methodological quality. Linking evidence to action Different interventions have their own sets of advantages for addressing cancer-related fatigue. These results can be utilized as evidence-based interventions for healthcare workers and patients to manage cancer-related fatigue.

Few studies have investigated the functional patterns of methamphetamine abstainers. A better understanding of the underlying neurobiological mechanism in the brains of methamphetamine abstainers will help to explain their abnormal behaviors. Forty-two male methamphetamine abstainers, currently in a long-term abstinence status (for at least 14 months), and 32 male healthy controls were recruited. All subjects underwent functional MRI while responding to drug-associated cues. This study proposes to combine a convolutional neural network with a short-time Fourier transform to identify different brain patterns between methamphetamine abstainers and controls. The short-time Fourier transformation provides time-localized frequency information, while the convolutional neural network extracts the structural features of the time–frequency spectrograms. The results showed that the classifier achieved a satisfactory performance (98.9% accuracy) and could extract robust brain voxel information. The highly discriminative power voxels were mainly concentrated in the left inferior orbital frontal gyrus, the bilateral postcentral gyri, and the bilateral paracentral lobules. This study provides a novel insight into the different functional patterns between methamphetamine abstainers and healthy controls. It also elucidates the pathological mechanism of methamphetamine abstainers from the view of time–frequency spectrograms.

Objective: The objective of this study was to evaluate whether the Chinese herbal medicine formula Guilu Erxian Jiao can improve the T-score in osteoporosis patients and even decrease the fracture rate.Design: This is a retrospective study.Subjects and Setting: Osteoporosis participants were selected from the Chang Gung Memorial Hospital (CGMH) database from 2000 to 2019.Interventions: The patients were administered Guilu Erxian Jiao pills.Outcome measures: We analyzed the change of T-score and the associated cumulative incidence of fracture.Results: Eighty-five patients administered GEJ met the inclusion criteria. After propensity score matching (1:5), 425 patients who were not administered GEJ were included in the control group. There were no significant differences about the baseline characteristics between the study and control groups. In the study group, GEJ improved the osteoporosis of the lumbar vertebrate and osteopenia of the hip joint but did not improve osteoporosis of the femoral neck. The cumulative rate of fracture between these two groups was not significantly different. Patients who took at least 600 GEJ pills over the treatment period had a decreased risk for fracture at fracture-prone sites.Conclusion:The use of Guilu Erxian Jiao may improve osteoporosis of the lumbar vertebrate and osteopenia of the hip joint. In addition, it may help decrease fractures of the lumbar spine. Administering at least 600 GEJ pills over the treatment period might result in a decreased risk for fracture at fracture-prone sites.

Pathologic conditions in which the body׳s own response to an insult is the most damaging aspect of the disease, such as in auto-immunity and sepsis, have seen researchers and clinicians struggle to find therapeutic targets for decades. Large clinical cohorts and advanced molecular biology are key elements in the search for new medications. Methodology with increasing resolution is constantly being developed to identify new subsets of cells embedded in the disease framework and to map their complex gene expression profile, secretome and epigenome. Big data that is thus being generated require advanced computational methods in order to distil knowledge from them, and in order to use them as the basis for modeling approaches. Models need to integrate the spatial, temporal and organizational domains in order to reflect biology with a certain degree of fidelity. The ultimate goal of the combined efforts of clinical studies, molecular biology with cutting-edge technology and comprehensive mathematical modeling is the bench-to-bedside translation of knowledge to reduce the socio-economic burden of disease.

Doxorubicin (DOX) could trigger congestive heart failure, which largely limited the clinical use of DOX. microRNAs (miRNAs) were closely involved in the pathogenesis of DOX-induced cardiomyopathy. Here, we aimed to investigate the effect of miR-152 on DOX-induced cardiotoxicity in mice. To study this, we used an adeno-associated viral vector to overexpress miR-152 in mice 6 weeks before DOX treatment, using a dose mimicking the concentrations used in the clinics. In response to DOX injection, miR-152 was significantly decreased in murine hearts and cardiomyocytes. After DOX treatment, mice with miR-152 overexpression in the hearts developed less cardiac dysfunction, oxidative stress, inflammation, and myocardial apoptosis. Furthermore, we found that miR-152 overexpression attenuated DOX-related oxidative stress, inflammation, and cell loss in cardiomyocytes, whereas miR-152 knockdown resulted in oxidative stress, inflammation, and cell loss in cardiomyocytes. Mechanistically, this effect of miR-152 was dependent on the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in response to DOX. Notably, Nrf2 deficiency blocked the protective effects of miR-152 against DOX-related cardiac injury in mice. In conclusion, miR-152 protected against DOX-induced cardiotoxicity via the activation of the Nrf2 signaling pathway. These results suggest that miR-152 may be a promising therapeutic target for the treatment of DOX-induced cardiotoxicity.

Coagulation is a common method used to remove suspended particulate matter (SPM) from the water supply. SPM has preferable adsorption ability for antibiotics in water; therefore, SPM adsorption and coagulation may be a possible way to remove tetracycline (TC) from water. This study carried out coagulation experiments combining SPM collected from a natural lake at a location with three common coagulants-polyaluminum sulfate, polyaluminum chloride, and polyferric sulfate-under different pH values, exploring the adsorption of TC by SPM, coagulation of SPM with TC, and the primary influencing factors of this process. The maximum removal rate of TC can reach 97.87% with an SPM concentration of 1000 mg/L. Multi-factor analysis of variance showed the importance of various TC removal factors, which were ranked as follows: SPM concentration ≫ initial TC concentration type of coagulant pH values. The higher the SPM concentration, the better the TC removal (p 0.001). Fourier infrared spectroscopy results demonstrated the strong adsorption effect of SPM on TC after being combined with a coagulant, and scanning electron microscopy also indicated that SPM becomes effective nuclei in the coagulation process, which is a possible reason for better TC removal. However, the effluent turbidities under 1000 mg/L SPM concentrations were high without coagulant aid. With the addition of coagulant aid anion polyacrylamide, the TC removal remained unchanged, effluent turbidity significantly reduced, and the TC desorption became low. These results indicate that applying SPM from natural lakes in the coagulation process could potentially remove TC in water.

Postpartum depression (PPD) is a major public health problem worldwide, which adversely affects maternal and infant health. The purpose of this study was to determine the prevalence and related factors of postpartum depression in Chinese puerperium women.A cross-sectional study was conducted in Baoan Maternal and Child Health Hospital located in the west of Shenzhen, China. The Chinese version of the Edinburgh Postpartum Depression Scale (EPDS) was used to screen PPD. A score of ≥10 was used as the threshold of postpartum depression.A total of 4813 puerperal women were included in this study, 11.5% of whom were considered to have PPD. Multivariate logistic regression analysis found that family history of mental illness (OR = 1.94; 95% CI, 1.05-3.57; P = 0.033), living with parents-in-law (OR = 1.41; 95% CI, 1.16-1.72; P0.001), anxiety during pregnancy (OR = 3.66; 95% CI, 2.97-4. 52; P0.001), depression during pregnancy (OR = 4.25; 95% CI, 3.28-5.50; P0.001), and stressful life events (OR = 1.50; 95% CI, 1.03-2.20; P = 0.036) were associated with the high prevalence of PPD.The cross-sectional survey cannot assess direct causality. EPDS is just a screening tool and not a diagnostic one.Postpartum depression is a common disease in Chinese puerperal population. High-risk pregnant women with postpartum depression need routine screening and targeted intervention for PPD.

Background: The coronavirus disease 2019 (COVID-19) has been rapidly transmitted worldwide, which contributed to various psychological problems (such as fear, depression, and anxiety) among the general population in China. The purpose of this study is to investigate the prevalence and associated factors of depressive symptoms among Chinese adults.Methods: A cross-sectional study of Chinese adults was conducted during 17–29 February 2020. Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression scale (CES-D).Results: A total of 3,399 respondents were included in the analysis. It was observed that 14.2% (481/3,399) of the participants were screened positive for depressive symptoms. In a multivariate logistic regression analysis, older age (OR = 0.98; 95% CI, 0.97–0.99), smoking (OR = 1.57; 95% CI, 1.10–2.26), self-rated health (good: OR = 0.49; 95% CI, 0.37–0.66; fairly: OR = 0.60; 95% CI, 0.45–0.80), having greater support scores (OR = 0.95; 95% CI, 0.94–0.96), knowledge about the main symptom of COVID-19 (very clearly: OR = 0.58; 95% CI, 0.42–0.79; relatively clearly: OR = 0.59; 95% CI, 0.44–0.79), and staying in Wuhan within 3 months before the outbreak of epidemic (OR = 1.78; 95% CI, 1.34–2.38) were associated with depressive symptoms.Conclusion: A considerable proportion of the general population in China had depressive symptoms during the COVID-19 epidemic. Routine screening and targeted interventions for depression are needed among high-risk depressed individuals during the COVID-19 epidemic.

Study design This was a Bayesian network meta-analysis. Objective We aimed to assess the comparative efficacies of the 5 most commonly used procedures for spondylolisthesis in a Bayesian network meta-analysis. Summary of background Lumbar fusion procedures are the backbone for the surgical treatment of spondylolisthesis. However, the current evidence has only considered head-to-head comparisons of different fusion procedures and failed to definitively favor one fusion procedure over another. Materials and methods A Bayesian random-effects model was used, and radiographic fusion and complications were assessed by risk ratio with a corresponding 95% credible interval; Oswestry Disability Index (ODI) scores were assessed by mean difference and 95% credible interval. Furthermore, with respect to each endpoint, ranking probabilities for each fusion procedure were evaluated using the value of the surface under the cumulative ranking curve. Results In all, 12 studies were identified. Significant differences in associated complications were found between minimally invasive transforaminal lumbar interbody fusion (MTLIF) and each of the other 4 fusion procedures. Surface under the cumulative ranking curve results suggested that for the most effective radiographic fusion, open transforaminal lumbar interbody fusion (OTLIF) had the maximum probability of being successful (76.6%), followed by MTLIF (70.4%) and open posterior lumbar interbody fusion (OPLIF, 48.7%). In terms of ODI scores, OTLIF might be the best intervention (70.5%), followed by MTLIF (68.8%) and then OPLIF (44.0%). However, MTLIF is ranked the safest (99.8%) regarding associated complications, followed sequentially by OTLIF (57.1%) and posterolateral fusion (30.1%). Conclusions OTLIF for spondylolisthesis was found to be the more efficient procedure in terms of radiographic fusion and ODI scores. Importantly, MTLIF is most likely to have a lower associated complication rate compared with other fusion procedures.

Dendritic cells (DCs) are professional antigen-presenting cells that induce and regulate adaptive immunity by presenting antigens to T cells. Due to their coordinative role in adaptive immune responses, DCs have been used as cell-based therapeutic vaccination against cancer. The capacity of DCs to induce a therapeutic immune response can be enhanced by re-wiring of cellular signalling pathways with microRNAs (miRNAs). Since the activation and maturation of DCs is controlled by an interconnected signalling network, we deploy an approach that combines RNA sequencing data and systems biology methods to delineate miRNA-based strategies that enhance DC-elicited immune responses.Through RNA sequencing of IKKβ-matured DCs that are currently being tested in a clinical trial on therapeutic anti-cancer vaccination, we identified 44 differentially expressed miRNAs. According to a network analysis, most of these miRNAs regulate targets that are linked to immune pathways, such as cytokine and interleukin signalling. We employed a network topology-oriented scoring model to rank the miRNAs, analysed their impact on immunogenic potency of DCs, and identified dozens of promising miRNA candidates with miR-15a and miR-16 as the top ones. The results of our analysis are incorporated in a database which constitutes a tool to identify DC-relevant miRNA-gene interactions with therapeutic potential (www.synmirapy.net/dc-optimization).

Background: Mild cognitive impairment (MCI) is the early phase of Alzheimer's disease (AD). The aim of early intervention for MCI is to decrease the rate of conversion from MCI to AD. However, the efficacy of multiple interventions in MCI, and the optimal methods of delivery, remain controversial. We aimed to compare and rank the treatment methods for MCI in AD, in order to find an optimal intervention for MCI and a way to prevent or delay the occurrence of AD. Methods: Pair-wise and network meta-analysis were conducted to integrate the treatment effectiveness through direct and indirect evidence. Four English databases and three Chinese databases were searched for international registers of eligible published, single or double blind, randomized controlled trials up to September 31st 2019. We included nine comparative interventions: pharmacological therapies which incorporated cholinesterase inhibitors (ChEI), ginkgo, nimodipine, and Chinese medicine; non-pharmacological therapies comprising of acupuncture, music therapy, exercise therapy, and nutrition therapy; and a placebo group. The primary outcome was the Mini-Mental State Examination (MMSE) score. The secondary outcome was the AD Assessment Scale-cognitive subscale (ADAS-cog). Results: Twenty-eight trials were eligible, including 6,863 participants. In the direct meta-analysis, as for the Mini-Mental State Examination scale, the ChEIs (MD: -0.38; 95% CI: -0.74, -0.01), Chinese medicine (MD: -0.31; 95% CI: -0.75, 0.13), exercise therapy (MD: -0.50; 95% CI: -0.65, -0.35), music therapy (MD: -1.71; 95% CI: -4.49, 1.07), were statistically more efficient than placebo. For AD Assessment Scalecognitive subscale outcome, ChEIs (MD: 1.20; 95% CI: 0.73, 1.68), Acupuncture (MD: 1.36; 95% CI: 1.28, 1.44), Chinese medicine (MD: 0.61; 95% CI: 0.49, 0.73) and exercise (MD: 0.61; 95% CI: 0.49, 0.73) were better than placebo. In the network meta-analysis, the MMSE outcome ranked music therapy (59%) as the best and Acupuncture (26%) as second. Nutrition and Ginkgo treatment had the lowest rank among all interventions. For ADAS-cog outcome, acupuncture (52) ranked the best. Conclusion: Among the nine treatments studied, music therapy appears to be the best treatment for MCI, followed by acupuncture. Our study provides new insights into potential clinical treatments for MCI due to AD, and may aid the development of guidelines for MCI in AD.

COVID-19 has been announced pandemic by WHO and over 17,000,000 people infected (Till April 21st 2020). The disease is currently under control in China, with a curative rate of 86.8%. Chloroquine (CQ) is an old anti-malarial drug with good tolerability, which had proved to be effective in previous SARS-coronavirus, which spread and disappeared between 2002-2003. In vitro studies demonstrated the efficacy of CQ in curing COVID-19. Consequently, via analytical PBPK modeling, a further preliminary clinical trial has proved the efficacy and safety of CQ in China., and multiple clinical trials were registered and approved to investigate the activity of other analogs of CQ against COVID-19. We have listed all the clinical trials and made a meta-analysis of published data of hydroxychloroquine (HCQ). HCQ could increase the CT improvement and adverse reactions (ADRs) significantly though there was considerable heterogeneity among current researches. Actually, CQ and its analogs have unique pharmacokinetic characteristics, which would induce severe side effects in some circumstances. We have then summarized pharmacological considerations for these drugs so as to provide to the busy clinicians to avoid potential side effects when administered CQ or its analogs to COVID-19 patients, especially in the elderly, pediatrics, and pregnancies.

Breast cancer (BC) is a common malignancy worldwide. More than 3 700 000 women die of BC every year. DSCAM-AS1 was overexpressed several kinds of cancer and miR-204-5p was lowly expressed, which indicated that miR-204-5p had anti-tumor activity and DSCAM-AS1 had pro-tumor activity. We intended to analyze DSCAM-AS1, miR-204-5p, and ribonucleotide reductase M2 (RRM2). Microarray analysis and quantitative Real Time fluorescence Polymerase Chain Reaction (qRT-PCR) were employed to determine DSCAM-AS1 and miR-204-5p expression. Luciferase reporter assay was applied to examine the target relationship between DSCAM-AS1, miR-204-5p, and RRM2. Cell Counting Kit-8 (CCK-8 assay), transwell assay, and flow cytometry were used to detect cell proliferation, invasion, and apoptosis. The expression of DSCAM-AS1, miR-204-5p, and RRM2 were confirmed by Western blot. We also conducted in vivo assay to verify the effect of DSCAM-AS1. DSCAM-AS1 was up-regulated, while miR-204-5p was down-regulated in BC tissues and cells. DSCAM-AS1 directly targeted miR-204-5p. DSCAM-AS1 promoted the proliferation and invasion of BC cells by reducing miR-204-5p and inhibiting miR-204-5p expression. DSCAM-AS1 expression was related to the expression of RRM2, and miR-204-5p could reverse the function of DSCAM-AS1. RRM2 was up-regulated in BC cells, and miR-204-5p inhibited RRM2 expression by targeting RRM2. Overexpression of RRM2 stimulated proliferation and cell invasion and impeded apoptosis. In vivo experiments showed that knockdown of DSCAM-AS1 decreased the tumorigenesis of BC cells, increased the expression of miR-204-5p. DSCAM-AS1 promoted proliferation and impaired apoptosis of BC cells by reducing miR-204-5p and enhancing RRM2 expression. DSCAM-AS1/miR-204-5p/RRM2 may serve as novel therapeutic targets for BC.

Nickel cobalt sulfide (Ni-Co-S) is one of the most potential electrocapacitive materials for energy storage devices, owing to the high electrical conductivity and multiple oxidation states. Large surface area and efficient charge/ion transfer routes are dispensable for an efficient electrocapacitive material. The rational-designed core/shell structures are fabricated in this work by first synthesizing the Ni-Co-S nanosheet array on the Ni foam using a hydrothermal reaction as the core and then depositing the cobalt sulfide (Co-S) nanosheets as the shell via electrodeposition. The electrodepositing cycles are varied to synthesize the Co-S shell with different sizes and densities. The highest specific capacitance (CF) of 8.47 F/cm2corresponding to the capacity of 1.65 mAh/cm2are obtained at 5 mV/s for the optimized Ni-Co-S/Co-S electrode prepared using 40 cycles for electrodeposition, due to the larger surface area of the sheet-on-sheet structure and the suitable size of the gaps between nanosheets for efficient ions diffusion. A CF value of714.2 mF/cm2 at 5 mA/cm2, a potential window of 1.6 V, and a CF retention of 65% after 5000 cycles repeated charge/discharge process are achieved for an asymmetric supercapacitor assembled using the optimized Ni-Co-S/Co-S electrode as the positive electrode and an activated carbon electrode as the negative electrode.

Molybdate based phosphors have efficient absorption in the ultraviolet (UV) region and can be used for UV-pumped light emitting. A series of NaGd0.5Tb0.5−xEux(MoO4)2 (0 ≤ x ≤ 0.5) multicolor tunable phosphors were prepared via a conventional solid-state reaction method. The as-prepared samples were well characterized by x-ray diffraction patterns, Fourier transform infrared spectroscopy, scanning electronic microscope, electron energy-dispersive spectroscopy, UV–vis diffused reflectance, photoluminescent spectra, decay curve and temperature-dependent photoluminescence spectra. The results indicate that the NaGd0.5Tb0.5−xEux(MoO4)2 (0 ≤ x ≤ 0.5) phosphors exhibit a good crystallinity and form a continuous solid solution with scheelite structure. Under UV excitation, NaGd0.5Tb0.5−xEux(MoO4)2 (0 ≤ x ≤ 0.5) phosphors exhibit characteristic emissions of Tb3+ (5D4 → 7FJ, J = 6, 5, 4, 3) and Eu3+ (5D0 → 7FJ, J = 0, 1, 2, 3, 4). The host NaGd(MoO4)2 has excellent energy transfer efficiency for rare earth ions, and the energy transfer from Tb3+ ions to Eu3+ ions is efficient, which can be confirmed by the decay curve. The energy transfer (ET) process between Tb3+ and Eu3+ was demonstrated to a reasonable type via a dipole–dipole interaction with ET efficiency of about nearly 95%. Moreover, the temperature-dependent luminescence properties indicated that the phosphors possessed good thermal stability. Interestingly, the luminescence color of NaGd0.5Tb0.5−xEux(MoO4)2 phosphors can be easily tuned from green to green-yellow, yellow, orange-yellow and ultimately to red by simply adjusting the related concentrations of Tb3+ and Eu3+ under a single wavelength excitation, which might have potential applications in the fields of as multi-color display and illumination.

CircRNAs exert gene regulatory effects by sequestering target microRNAs (miRNAs) and play a vital role in the onset and development of disease. Until recently, little has been known about the expression, regulation and biological function of circRNAs in both health and chronic hepatitis B (CHB).To identify hepatic circRNAs associated with CHB, we performed RNA sequencing using liver biopsies from untreated CHB patients and controls. We then established a bioinformatics pipeline for identification of CHB-associated circRNAs and in silico analysis of the circRNA-miRNA-mRNA pathways. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to confirm these results. The profiles of hepatic circRNA expression were significantly different in CHB compared with controls, with a total of 99 dysregulated circRNAs identified to be correlated with CHB. Computational analysis of the circRNA-miRNA-mRNA pathways revealed a large number of miRNAs (665), which were putatively targeted by the differentially expressed hepatic circRNAs. Interestingly, four of the predicted CHB-related circRNA-miRNA-mRNA pathways were found to be involved in the pathogenesis of HBV infection and progression of HBV-associated liver disease. Among these pathways, regression analysis of gene expression revealed a strong positive correlation between hsa_circ_0000650 and TGFβ2 and a negative correlation between hsa_circ_0000650 and miR-6873-3p, which hinted that hsa_circ_0000650 interacted with TGFβ2 mediated by miR-6873-3p. This study firstly demonstrates that patients with CHB present different profiles of hepatic circRNAs and circRNA/miRNA interactions. Thus, circRNAs have promise as novel mechanisms underlying the pathogenesis and progression of CHB.

Motivation Extracellular vesicles (EVs), including exosomes and microvesicles, are potent and clinically valuable tools for early diagnosis, prognosis and potentially the targeted treatment of cancer. The content of EVs is closely related to the type and status of the EV-secreting cell. Circulating exosomes are a source of stable RNAs including mRNAs, microRNAs and long non-coding RNAs (lncRNAs). Results This review outlines the links between EVs, lncRNAs and cancer. We highlight communication networks involving the tumor microenvironment, the immune system and metastasis. We show examples supporting the value of exosomal lncRNAs as cancer biomarkers and therapeutic targets. We demonstrate how a system biology approach can be used to model cell–cell communication via exosomal lncRNAs and to simulate effects of therapeutic interventions. In addition, we introduce algorithms and bioinformatics resources for the discovery of tumor-specific lncRNAs and tools that are applied to determine exosome content and lncRNA function. Finally, this review provides a comprehensive collection and guide to databases for exosomal lncRNAs. Supplementary information Supplementary data are available at Bioinformatics online.

La2−xEuxMo2O9 (0 ≤ x ≤ 0.6) solid solution microcrystals have been successfully fabricated by a facile hydrothermal derived synthesis process (i.e. the precursors were obtained via hydrothermal treat at 180 °C for 24 h and then calcined at 600 °C for 5 h). X-ray diffraction (XRD), scanning electron microscope (SEM), photoluminescence excitation and emission spectra (PL) and photoluminescence decay curves were used to characterize La2−xEuxMo2O9 samples. The effects of the Eu3+ ions concentration on the luminescence of the La2−xEuxMo2O9 microcrystals were also investigated in detail. The results show that the obtained La2−xEuxMo2O9 microcrystals are cubic phase continuous solid solution, and all can be efficiently excited by 335 nm ultraviolet and 464 nm blue light, exhibiting the strong red emission at 615 nm of Eu3+ ion. The obtained La2−xEuxMo2O9 microcrystals are promising red-emitting phosphors pumped by near-UV or blue light for the white light emitting diodes (WLEDs).

Hepatitis B e antigen (HBeAg) seroconversion is considered to have significantly favourable clinical outcomes for patients with chronic hepatitis B (CHB). However, inconsistent study results suggest that hepatocellular carcinoma (HCC) still occurs in patients with HBeAg seroconversion. We performed a systematic review and meta-analysis to determine the incidence of HCC in patients with CHB after HBeAg seroconversion. Web of Science, PubMed and Embase databases were searched through January 2017. The incidence of HCC in CHB patients after HBeAg seroconversion was pooled using a random-effects model or fix-effects model. Sixteen studies were finally included, involving 4910 patients with HBeAg seroconversion. The overall pooled proportion suggested that 3.33% (95% confidence interval (CI): 2.28%-4.58%) of patients with CHB develop HCC despite HBeAg seroconversion. In patients with HBeAg seroconversion without cirrhosis, the pooled proportion of HCC development was 0.94% (95% CI: 0.15%-2.4%). Moreover, patients with cirrhosis, active hepatitis, or aged greater than 40 years at the time of HBeAg seroconversion were at significantly higher risk for HCC development. HBeAg seroconversion was significantly associated with a reduced risk of HCC compared with persistently positive HBeAg (RR = 0.58, 95% CI: 0.35-0.97, P = .04). Despite the reduced risk with HBeAg seroconversion, HCC can still occur in a proportion of patients with CHB after HBeAg seroconversion. Long-term monitoring is needed for patients with established cirrhosis, active hepatitis or those older than 40 years at the time of HBeAg seroconversion.

In the past decade, risk-adjusted control charts have been widely used to monitor surgical outcomes. However, most existing approaches focus on monitoring shifts in location parameters and may not ...

Mitochondrial abnormality is frequently reported in individuals with hepatitis B virus (HBV) infection, but the associated hosts’ mitochondrial genetic factors remain obscure. We hypothesized that mitochondria may affect host susceptibility to HBV infection. In this study, we aimed to detect the association between chronic HBV infection and mitochondrial DNA in Chinese from Yunnan, Southwest China. A total of 272 individuals with chronic HBV infection (CHB), 310 who had never been infected by HBV (healthy controls, HC) and 278 with a trace of HBV infection (spontaneously recovered, SR) were analysed for mtDNA sequence variations and classified into respective haplogroups. Haplogroup frequencies were compared between HBV infected patients, HCs and SRs. Haplogroup D5 presented a higher frequency in CHBs than in HCs (P = 0.017, OR = 2.87, 95% confidence interval [CI] = (1.21–6.81)) and SRs (P = 0.049, OR = 2.90, 95% CI = 1.01–8.35). The network of haplogroup D5 revealed a distinct distribution pattern between CHBs and non-CHBs. A trend of higher viral load among CHBs with haplogroup D5 was observed. Our results indicate the risk potential of mtDNA haplogroup D5 in chronic HBV infection in Yunnan, China.

Background Premature infants are prone to suffer multisystem complications after birth due to the incomplete development of organ tissues and low immunity, and they require a longer period of supervised treatment in the neonatal intensive care unit (NICU). However, due to the specificity of medical care in the NICU, the sleep of preterm infants is highly susceptible that has an impact on the prognosis of preterm infants. Recently, various non-pharmacological interventions have been applied to the sleep of preterm infants in the NICU, which have shown positive outcomes. However, the efficacy and safety of them are unclear. This study aims to evaluate the effects of non-pharmacological interventions on sleep in preterm infants in the NICU through a network meta-analysis. Methods Randomized controlled trials of non-pharmacological interventions on sleep in preterm infants in the NICU published before September 2021 will be searched in online databases, including the Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, Wanfang, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, and Web of Science. Two researchers will be independently responsible for screening and selecting eligible literatures, extracting data and evaluating the risk of bias in the included studies. Stata 14.0 software will be used for data analysis. Results The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion This study will provide comprehensive and reliable evidence-based references for the efficacy and safety in different non-pharmacological interventions on sleep in preterm infants in the NICU.

Graphene oxide (GO), a two-dimensional material with a high aspect ratio and polar functional groups, can physically adsorb single-strand DNA through different types of interactions, such as hydrogen bonding and π-π stacking, making it an attractive nanocarrier for nucleic acids. In this work, we demonstrate a strategy to target exosites I and II of thrombin simultaneously by using programmed hybrid-aptamers for enhanced anticoagulation efficiency and stability. The targeting ligand is denoted as Supra-TBA15/29 (supramolecular TBA15/29), containing TBA15 (a 15-base nucleotide, targeting exosite I of thrombin) and TBA29 (a 29-base nucleotide, targeting exosite II of thrombin), and it is designed to allow consecutive hybridization of TBA15 and TBA29 to form a network of TBAs (i.e., supra-TBA15/29). The programmed hybrid-aptamers (Supra-TBA15/29) were self-assembled on GO to further boost anticoagulation activity by inhibiting thrombin activity, and thus suppress the thrombin-induced fibrin formation from fibrinogen. The Supra-TBA15/29-GO composite was formed mainly through multivalent interaction between poly(adenine) from Supra-TBA15/29 and GO. We controlled the assembly of Supra-TBA15/29 on GO by regulating the preparation temperature and the concentration ratio of Supra-TBA15/29 to GO to optimize the distance between TBA15 and TBA29 units, aptamer density, and aptamer orientation on the GO surfaces. The dose-dependent thrombin clotting time (TCT) delay caused by Supra-TBA15/29-GO was >10 times longer than that of common anticoagulant drugs including heparin, argatroban, hirudin, and warfarin. Supra-TBA15/29-GO exhibits high biocompatibility, which has been proved by in vitro cytotoxicity and hemolysis assays. In addition, the thromboelastography of whole-blood coagulation and rat-tail bleeding assays indicate the anticoagulation ability of Supra-TBA15/29-GO is superior to the most widely used anticoagulant (heparin). Our highly biocompatible Supra-TBA15/29-GO with strong multivalent interaction with thrombin [dissociation constant (Kd) = 1.9 × 10−11 M] shows great potential as an effective direct thrombin inhibitor for the treatment of hemostatic disorders.

Operated cancer patients develop elevated levels of extracellular vesicles (EVs) in their blood stream, suppressing cancer cells through miRNA-34a., Upon tumor development, new extracellular vesicles appear in circulation. Our knowledge of their relative abundance, function, and overall impact on cancer development is still preliminary. Here, we demonstrate that plasma extracellular vesicles (pEVs) of non-tumor origin are persistently increased in untreated and post-excision melanoma patients, exhibiting strong suppressive effects on the proliferation of tumor cells. Plasma vesicle numbers, miRNAs, and protein levels were elevated two- to tenfold and detected many years after tumor resection. The vesicles revealed individual and clinical stage-specific miRNA profiles as well as active ADAM10. However, whereas pEV from patients preventing tumor relapse down-regulated β-catenin and blocked tumor cell proliferation in an miR-34a–dependent manner, pEV from metastatic patients lost this ability and stimulated β-catenin–mediated transcription. Cancer-induced pEV may constitute an innate immune mechanism suppressing tumor cell activity including that of residual cancer cells present after primary surgery.

// Elke Nolte 1 , Sven Wach 1 , Izabella Thais Silva 2, 6 , Sabine Lukat 1 , Arif B. Ekici 3 , Jennifer Munkert 4 , Frieder Muller-Uri 4 , Wolfgang Kreis 4 , Claudia Maria Oliveira Simoes 2 , Julio Vera 5 , Bernd Wullich 1 , Helge Taubert 1 , Xin Lai 5 1 Department of Urology, University Hospital Erlangen, Erlangen, Germany 2 Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Florianopolis, Brazil 3 Institute of Human Genetics, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany 4 Department of Biology, Chair of Pharmaceutical Biology, Friedrich-Alexander-University Erlangen-Nurnberg, Erlangen, Germany 5 Laboratory of Systems Tumor Immunology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg, Erlangen, Germany 6 Department of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil Correspondence to: Xin Lai, email: xin.lai@uk-erlangen.de Keywords: 3β-[2-(1-amantadine)-1-on-ethylamine]-digitoxigenin, cardiac glycoside analog, human renal cell carcinoma cells, miRNA, cell cycle Received: June 21, 2016 Accepted: December 24, 2016 Published: January 14, 2017 ABSTRACT Cardiac glycosides are well known in the treatment of cardiovascular diseases; however, their application as treatment option for cancer patients is under discussion. We showed that the cardiac glycoside digitoxin and its analog AMANTADIG can inhibit the growth of renal cell carcinoma (RCC) cell lines and increase G2/M cell cycle arrest. To identify the signaling pathways and molecular basis of this G2/M arrest, microRNAs were profiled using microRNA arrays. Cardiac glycoside treatment significantly deregulated two microRNAs, miR-2278 and miR-670-5p. Pathway enrichment analysis showed that all cardiac glycoside treatments affected the MAPK and the axon guidance pathway. Within these pathways, three genes, MAPK1, NRAS and RAC2, were identified as in silico targets of the deregulated miRNAs. MAPK1 and NRAS are known regulators of G2/M cell cycle arrest. AMANTADIG treatment enhanced the expression of phosphorylated MAPK1 in 786-O cells. Secondly, we studied the expression of survivin known to be affected by cardiac glycosides and to regulate the G2/M cell phase. AMANTADIG treatment upregulated the expression of the pro-apoptotic survivin-2B variant in Caki-1 and 786-O cells. Moreover, treatment with AMANTADIG resulted in significantly lower survivin protein expression compared to 786-O control cells. Summarizing, treatment with all cardiac glycosides induced G2/M cell cycle arrest and downregulated the miR-2278 and miR-670-5p in microarray analysis. All cardiac glycosides affected the MAPK-pathway and survivin expression, both associated with the G2/M phase. Because cells in the G2/M phase are radio- and chemotherapy sensitive, cardiac glycosides like AMANTADIG could potentially improve the efficacy of radio- and/or chemotherapy in RCCs.

Background/Aims: Angiotensin II (Ang II) has been shown to promote cardiac remodeling during the process of hypertrophy. Myosin light chain kinase (MLCK), a specific kinase for the phosphorylation of myosin light chain 2 (MLC2), plays an important role in regulating cardiac muscle contraction and hypertrophy. However, whether Ang II could facilitate cardiac hypertrophy by altering the expression of MLCK remains unclear. This study aimed to investigate this effect and the underlying mechanisms. Methods: Cardiac hypertrophy was induced via pressure overload in rats, which were then evaluated via histological and biochemical measurements and echocardiography. Angiotensin-converting enzyme inhibitor (ACEI) was used to inhibit Ang II. Neonatal rat cardiomyocytes were stimulated with Ang II to induce hypertrophy and were treated with a matrix metalloproteinase 9 (MMP9) inhibitor. Myocyte hypertrophy was evaluated using immunofluorescence and qRT-PCR. Degradation of recombinant human MLCK by recombinant human MMP9 was tested using a cleavage assay. The expression levels of MLCK, MLC2, phospho-myosin light chain 2 (p-MLC2), myosin phosphatase 2 (MYPT2), and calmodulin (CaM) were measured using western blotting. Results: ACEI improved cardiac function and remodeling and increased the levels of MLCK and p-MLC2 as well as reduced the expression of MMP9 in pressure overload-induced cardiac hypertrophy. Moreover, the MMP9 inhibitor alleviated myocyte hypertrophy and upregulated the levels of MLCK and p-MLC2 in Ang II-induced cardiomyocyte hypertrophy. Recombinant human MLCK was concentration- and time-dependently degraded by recombinant human MMP9 in vitro, and this process was prevented by the MMP9 inhibitor. Conclusion: Our results suggest that Ang II is involved in the degradation of MLCK in pressure overload-induced cardiac hypertrophy and that this process was mediated by MMP9.

Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction (MI). Increasing evidence indicates that neuregulin-1 (NRG-1) improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups: sham (with the left anterior descending coronary artery exposed but without ligation), MI (left anterior descending coronary artery ligation), and MI plus NRG-1 (left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 (10 μg/kg, once daily for 7 days)). At 4 weeks after MI, echocardiography was used to detect the rat cardiac function by measuring the left ventricular end-systolic inner diameter, left ventricular diastolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. mRNA and protein expression levels of tyrosine hydroxylase, growth associated protein-43 (neuronal specific protein), nerve growth factor, choline acetyltransferase (vagus nerve marker), and vesicular acetylcholine transporter (cardiac vagal nerve fiber marker) in ischemic myocardia were detected by real-time PCR and western blot assay to assess autonomous nervous remodeling. After MI, the rat cardiac function deteriorated significantly, and it was significantly improved after NRG-1 injection. Compared with the MI group, mRNA and protein levels of tyrosine hydroxylase and growth associated protein-43, as well as choline acetyltransferase mRNA level significantly decreased in the MI plus NRG-1 group, while mRNA and protein levels of nerve growth factor and vesicular acetylcholine transporters, as well as choline acetyltransferase protein level slightly decreased. Our results indicate that NRG-1 can improve cardiac function and regulate sympathetic and vagus nerve remodeling post-MI, thus reaching a new balance of the autonomic nervous system to protect the heart from injury.

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal condition that can be primary or secondary. Secondary HLH due to Mycobacterium tuberculosis (TB) is uncommon. We report a case of tuberculosis-associated HLH in an umbilical cord blood transplant (UCBT) recipient and discuss its clinical characteristics and challenges. Methods Hematologic investigations, bone marrow aspirates, Xpert MTB/RIF test of TB with peripheral blood were performed. Immune modulation with anti-TB therapy was initiated. Results Subsequent treatment with anti-TB treatment resulted rapid clinical response and disease remission. Conclusion It is important to consider TB as one of the underlying cause of HLH in high-risk patients, particularly those in immunodeficient states. Early diagnosis and treatment can improve the survival rates of patients with tuberculosis-associated HLH.

Background: Reports on HBV genotype I in Vietnam, Laos, northeastern India, and China are limited and thus, no studies have examined HBV genotype I quasi species with coexistence of HBsAg and anti-HBs. Methods: The current study reports on an HBV genotype I quasi species isolated from a male patient (A02) showing coexistence of HBsAg and anti-HBs. The researchers identified a HBV strain isolated from a CHB patient from Zhaotong city, Yunnan province, China, who was infected with HBV genotype I and presented HBsAg and anti-HBs coexistence. In an effort to elucidate the mechanism underlying the coexistence of HBsAg and anti-HBs in this patient, the researchers performed full-length genome amplification, and the HBV strain was cloned to conduct a comprehensive analysis of mutations and to analyze quasi species variation in relation to the coexistence of HBsAg and anti-HBs. Results: The analysis indicated that the pre-core/core had the highest diversity, and HBsAg and MHBsAg accumulated more nonsynonymous mutations than synonymous mutations. Phylogenetic analyses and genotype identification suggest that A02 was infected with a putative genotype I strain. Unusual deletions of PreS (11 of 16 clones (69%) in PreS1) and amino acid variants of HBsAg (11 of 16 clones; 69%) were observed in the A02 quasi species that were associated with the coexistence of HBsAg and anti-HBs and other clinical features, thus conferring resistance to current antiviral therapies. Further functional studies are needed to assess the correlation between these variants and the coexistence of HBsAg and anti-HBs. Conclusions: The propensity for PreS1 deletions and the complexity of HBsAg variants in HBV isolates from a single patient infected with HBV genotype I could explain the coexistence of HBsAg and anti-HBs and the resistance to current antiviral therapies.

At present, few studies have focused on the impact of circulation patterns on aerosol pollution in the Pearl River delta region (PRD) region based on the objective circulation classification method. Based on PM2.5 observation data, meteorological observation data, Aerosol Robotic Network (AERONET) aerosol observation data and European Center for Medium-Range Weather Forecasting (ECMWF) ERA (European Reanalysis)-Interim data in the PRD during 2013 to 2017, the air pollution level, meteorological conditions, and aerosol optical and radiation characteristics in different circulation patterns are studied in this paper. Using ECMWF ERA-Interim sea level pressure, nine circulation patterns were determined based on the T-mode principal component analysis (PCA) combined with the k-means clustering method. There were significant differences in PM2.5 values under different circulation patterns, indicating that the change of atmospheric circulation is an important factor driving the change of air quality. The prevailing wind in winter (northerly wind) facilitates the transport of pollutants from the north of the PRD and forms severe air pollution, while the prevailing wind in summer (southerly wind) brings clean air from the South China Sea, additionally, a high frequency of precipitation benefits the wet scavenging of pollutants, resulting in improved air quality in the PRD region. The impact of circulation patterns on the AOD (aerosol optical depth) is basically similar to that of the PM2.5 concentration. The study also found that the annual average total radiation was negatively correlated with the annual average PM2.5 concentration. In future, we plan to identify which methods and data are suitable for circulation classification in the PRD region.

Fundus image analysis is crucial for eye condition screening and diagnosis and consequently personalized health management in a long term. This paper targets at left and right eye recognition, a basic module for fundus image analysis. We study how to automatically assign left-eye/right-eye labels to fundus images of posterior pole. For this under-explored task, four models are developed. Two of them are based on optic disc localization, using extremely simple max intensity and more advanced Faster R-CNN, respectively. The other two models require no localization, but perform holistic image classification using classical Local Binary Patterns (LBP) features and fine-tuned ResNet-18, respectively. The four models are tested on a real-world set of 1,633 fundus images from 834 subjects. Fine-tuned ResNet-18 has the highest accuracy of 0.9847. Interestingly, the LBP based model, with the trick of left-right contrastive classification, performs closely to the deep model, with an accuracy of 0.9718.

Background: Neonatal bacterial meningitis is a severe infection with high mortality and morbidity. It is necessary to identify factors associated with a high risk of a poor prognosis so that we can prevent them with more appropriate treatments. This study was performed to summarize the prognostic factors known to predict adverse outcomes in neonatal bacterial meningitis.Methods: The Medline/PubMed, Cochrane Library and Embase databases were searched for studies of prognostic risk factors in neonates with bacterial meningitis. Studies published from the initiation of the database to April 30th, 2017 were included. The quality of cohort studies was assessed by the Newcastle-Ottawa Scale (NOS). The quality of cross-section studies was assessed by the Agency for Healthcare Research and Quality (AHRQ) scale. Each prognostic factor known to cause adverse outcomes is summarized.Results: Sixteen studies were identified, including 7 cohort studies and 9 cross section studies. Seizure and high protein levels in the cerebrospinal fluid (CSF) predict a poor prognosis in this disease. Coma, the need for ventilation support, and leukopenia also had some value for predicting poor prognoses. A bulging anterior fontanelle was valuable for predicting mortality. Low CSF glucose levels, thrombocytopenia, gestational age (GA) < 37 weeks and an altered sensorium were correlated with a poor prognosis. A birth weight < 2500 g, early onset meningitis and positive CSF cultures were correlated with mortality.Conclusions: This study provides a preliminary exploration of prognostic factors in neonatal bacterial meningitis and thereby fills some of the gaps in the study of prognoses in this disease. These prognostic factors can be used to predict and estimate outcomes in neonatal bacterial meningitis. Without a meta-analysis, the reliability of these factors cannot be assured. In addition, these results emphasize that there is an urgent need for a standardized protocol for follow-up and well-designed prognostic studies in neonatal bacterial meningitis.