Search

Abstract. Background:. Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. Methods:. In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. Results:. In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962–1.000 in the training cohort and 0.969–0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. Conclusion:. ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. Trial Registration:. Chictr.org.cn: ChiCTR2200059599.

Background Computerised decision support systems (CDSS) are widely used by nurses and allied health professionals but their effect on clinical performance and patient outcomes is uncertain. Objectives Evaluate the effects of clinical decision support systems use on nurses’, midwives’ and allied health professionals’ performance and patient outcomes and sense-check the results with developers and users. Eligibility criteria Comparative studies (randomised controlled trials (RCTs), non-randomised trials, controlled before-and-after (CBA) studies, interrupted time series (ITS) and repeated measures studies comparing) of CDSS versus usual care from nurses, midwives or other allied health professionals. Information sources Nineteen bibliographic databases searched October 2019 and February 2021. Risk of bias Assessed using structured risk of bias guidelines; almost all included studies were at high risk of bias. Synthesis of results Heterogeneity between interventions and outcomes necessitated narrative synthesis and grouping by: similarity in focus or CDSS-type, targeted health professionals, patient group, outcomes reported and study design. Included studies Of 36,106 initial records, 262 studies were assessed for eligibility, with 35 included: 28 RCTs (80%), 3 CBA studies (8.6%), 3 ITS (8.6%) and 1 non-randomised trial, a total of 1318 health professionals and 67,595 patient participants. Few studies were multi-site and most focused on decision-making by nurses (71%) or paramedics (5.7%). Standalone, computer-based CDSS featured in 88.7% of the studies; only 8.6% of the studies involved ‘smart’ mobile or handheld technology. Care processes – including adherence to guidance – were positively influenced in 47% of the measures adopted. For example, nurses’ adherence to hand disinfection guidance, insulin dosing, on-time blood sampling, and documenting care were improved if they used CDSS. Patient care outcomes were statistically – if not always clinically – significantly improved in 40.7% of indicators. For example, lower numbers of falls and pressure ulcers, better glycaemic control, screening of malnutrition and obesity, and accurate triaging were features of professionals using CDSS compared to those who were not. Evidence limitations Allied health professionals (AHPs) were underrepresented compared to nurses; systems, studies and outcomes were heterogeneous, preventing statistical aggregation; very wide confidence intervals around effects meant clinical significance was questionable; decision and implementation theory that would have helped interpret effects – including null effects – was largely absent; economic data were scant and diverse, preventing estimation of overall cost-effectiveness. Interpretation CDSS can positively influence selected aspects of nurses’, midwives’ and AHPs’ performance and care outcomes. Comparative research is generally of low quality and outcomes wide ranging and heterogeneous. After more than a decade of synthesised research into CDSS in healthcare professions other than medicine, the effect on processes and outcomes remains uncertain. Higher-quality, theoretically informed, evaluative research that addresses the economics of CDSS development and implementation is still required. Future work Developing nursing CDSS and primary research evaluation. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in Health and Social Care Delivery Research; 2023. See the NIHR Journals Library website for further project information. Registration PROSPERO 1 [number: CRD42019147773]. Plain language summary Computerised decision support systems (CDSS) are software or computer-based technologies providing advice to professionals making clinical decisions – for example, which patients to treat first in emergency departments. CDSS improve some doctors’ decisions and patients’ outcomes, but we don’t know if they improve nurses’, midwives’ and therapists’ or other staff decisions and patient outcomes. Research into, and health professionals’ use of, technology – for example, in video consultations – has grown since the last relevant systematic review in 2009. We systematically searched electronic databases for research measuring how well nurses, midwifes and other therapists/staff followed CDSS advice, how CDSS influence their decisions, how safe CDSS are, and their financial costs and benefits. We interviewed CDSS users and developers and some patient representatives from a general practice to help understand our findings. Of 35 relevant studies – from 36,106 initially found – most (71%) focused on nurses. Just over half (57%) involved hospital-based staff, and three-quarters (75%) were from richer countries like the USA or the UK. Research quality had not noticeably improved since 2009 and all studies were at risk of potentially misleading readers. CDSS improved care in just under half (47%) of professional behaviours, such as following hand-disinfection guidance, working out insulin doses, and sampling blood on time. Patient care – judged using outcomes like falls, pressure ulcers, diabetes control and triage accuracy – was better in 41% of the care measured. There wasn’t enough evidence to judge CDSS safety or the financial costs and benefits of systems. CDSS can improve some nursing and therapist decisions and some patient outcomes. Studies mostly measure different behaviours and outcomes, making comparing them hard. Theories explaining or predicting how decision support systems might work are not used enough when designing, implementing or evaluating CDSS. More research into the financial costs and benefits of CDSS and higher-quality evidence of their effects are still needed. Whether decision support for nurses, midwives and other therapists reliably improves decision-making remains uncertain.

The global monkeypox virus (MPXV) outbreak in 2022 emphasizes the urgent need for effective and accessible new-generation vaccines and neutralizing antibodies. Herein, we identified MPXV-neutralizing antibodies using high-throughput single-cell RNA and V(D)J sequencing of antigen-sorted B cells from patients with convalescent monkeypox. IgG1-expressing B cells were obtained from 34 paired heavy- and light-chain B cell receptor sequences. Subsequently, three potent neutralizing antibodies, MV127, MV128, and MV129, were identified and reacted with the MPXV A35 protein. Among these, MV129, which has a half-maximal inhibitory concentration of 2.68μg/mL against authentic MPXV, was considered to be the putative candidates for MPXV neutralization in response to monkeypox disease.

ABSTRACT Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/μL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV.IMPORTANCEThe ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

Abstract Background Dengue is an important public health problem, which caused by the dengue virus (DENV), a single-stranded RNA virus consisted of four serotypes. Central nervus system (CNS) impairment in dengue usually results from DENV-2 or DENV-3 infection, which lead to life-threatening outcomes. Furthermore, neurological complications due to DENV-1 was rare especially in adult patients. Case presentation A 44-year-old man without comorbidities had lethargy after hyperpyrexia and a positive DENV NS1 antigen was detected for confirming the diagnosis of dengue on day 8 of onset. Then logagnosia, decreased muscle strength, delirium and irritability were occurred even radiographic examination were normal. He was treated with low-dose hormone, sedatives and gamma goblin with a short duration of 6 days. The cerebrospinal fluid (CSF) tests were persistent normal. However, presence of DENV-1 RNA was confirmed both in CSF and serum. Furthermore, the complete sequence of the DENV isolated from the patient’s serum was performed (GenBank No.: MW261838). The cytokines as IL-6, IL-10 and sVCAM-1 were increased in critical phase of disease. Finally, the patient was discharged on day 24 of onset without any neurological sequelae. Conclusion Encephalopathy caused by a direct CNS invasion due to DENV-1 during viremia was described in an adult patient. Treatment with low-dose hormone and gamma goblin was helpful for admission.

Abstract Osteosarcoma is generally considered a cold tumor and is characterized by epigenetic alterations. Although tumor cells are surrounded by many immune cells such as macrophages, T cells may be suppressed, be inactivated, or not be presented due to various mechanisms, which usually results in poor prognosis and insensitivity to immunotherapy. Immunotherapy is considered a promising anti-cancer therapy in osteosarcoma but requires more research, but osteosarcoma does not currently respond well to this therapy. The cancer immunity cycle (CIC) is essential for anti-tumor immunity, and is epigenetically regulated. Therefore, it is possible to modulate the immune microenvironment of osteosarcoma by targeting epigenetic factors. In this study, we explored the correlation between epigenetic modulation and CIC in osteosarcoma through bioinformatic methods. Based on the RNA data from TARGET and GSE21257 cohorts, we identified epigenetic related subtypes by NMF clustering and constructed a clinical prognostic model by the LASSO algorithm. ESTIMATE, Cibersort, and xCell algorithms were applied to analyze the tumor microenvironment. Based on eight epigenetic biomarkers (SFMBT2, SP140, CBX5, HMGN2, SMARCA4, PSIP1, ACTR6, and CHD2), two subtypes were identified, and they are mainly distinguished by immune response and cell cycle regulation. After excluding ACTR6 by LASSO regression, the prognostic model was established and it exhibited good predictive efficacy. The risk score showed a strong correlation with the tumor microenvironment, drug sensitivity and many immune checkpoints. In summary, our study sheds a new light on the CIC-related epigenetic modulation mechanism of osteosarcoma and helps search for potential drugs for osteosarcoma treatment.

Abstract Background For people at high risk of lung cancer, low-dose computed tomography (LDCT) is proposed as a method to reduce mortality. Methods Our objective was to estimate the effect of LDCT lung cancer screening on mortality in high-risk populations. A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (such as chest X-ray (CXR)) was conducted. RCTs of CXR screening were additionally included in the network meta-analyses. Bibliographic sources including MEDLINE, Embase, Web of Science and the Cochrane Library were searched to January 2017, and then further extended to November 2021. All key review steps were done by two persons. Quality assessment used the Cochrane Risk of Bias tool. Meta-analyses were performed. Results Nine RCTs, with up to 12.3 years of follow-up from randomisation, were included in the direct meta-analysis, which showed that LDCT screening was associated with a statistically significant decrease in lung cancer mortality (pooled relative risk (RR) 0.86, 95% confidence interval [CI] 0.77 to 0.96). There was a statistically non-significant decrease in all-cause mortality (pooled RR 0.98, 95% CI 0.95 to 1.01). The statistical heterogeneity for both outcomes was minimal. Network meta-analysis including the nine RCTs in the direct meta-analysis plus two further RCTs comparing CXR with usual care confirmed the size of the effect of LDCT on lung cancer mortality and that this was very similar irrespective of whether the comparator was usual care or CXR screening. Conclusions LDCT screening is effective in reducing lung cancer mortality in high-risk populations. The uncertainty of its effect on lung cancer mortality observed in 2018 has been much reduced with new trial results and updates to existing trials, emphasising the importance of updating systematic reviews. Although there are still a number of RCTs unreported or in progress, we predict that further evolution of summary mortality estimates is unlikely. The focus for debate now moves to resolving uncertainty about the cost-effectiveness of LDCT screening taking into account the balance between benefits and harms which occur in all screening programmes.

The monkeypox (mpox) virus has caused worldwide transmission since its initial report in England in early May 2022. Available data from the World Health Organization (WHO) show that Europe and the Americas experienced a huge wave of mpox virus infection. Now the number of infected cases is on the rise in Asia. Several sporadic infections have been reported in China. In this study, we obtained high-quality whole viral genomic sequences using a mpox virus-specific amplicon-based sequencing strategy. Our analysis of the phylogenomic characteristics indicated that all eight mpox virus sequences from Guangzhou belonged to the clade IIb lineage B.1.3 cluster. However, we could not locate the exact origins where the virus was imported, based on all the available mpox virus sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database (https://gisaid.org/), except for their closest sequence similarity to that was reported from Japan. Novel amino acid mutations were found among the eight cases, suggesting that a local transmission may have occurred in Guangzhou, China.

BackgroundMonkeypox virus (MPXV) is spreading globally and nearly half of the infected people were human immunodeficiency virus (HIV) positive. Therefore, an in-depth understanding of the effects of HIV infection on the outcomes of MPXV infection is urgently needed. This study aimed to explore the clinical features, viral dynamics, and antibody response to MPXV infections in men who had sex with men (MSM) with and without HIV co-infection.Design or methodsMPXV-infected patients diagnosed by PCR were recruited in this study and were divided into MPXV and MPXV + HIV groups based on whether they were co-infected with HIV. Clinical data and samples were collected during of the hospital stay and follow up interviews. The symptoms and signs, laboratory examinations, viral shedding in various body fluids or swabs, antibody dynamics were tracked and compared between the two groups.ResultsA total of 41 MPXV patients were recruited through June 2023 to September 2023 in Guangzhou. The MPXV group and MPXV + HIV group comprised 20 and 21 MSM, respectively. Patients in the two groups exhibited similar clinical characteristics except for pruritus and eschar, both were significantly fewer in MPXV + HIV group than in MPXV only group. Among the 355 clinical samples collected, MPXV DNA was detected in 100% of scabs, 97.4% of skin swabs, and 92.3% of exudate swabs from lesions, while the positive rate was 87.5% from oropharyngeal swabs, 59% from saliva, 51.3% from anal swabs, 50% from feces, 30.6% from urine samples, 37.5% of semen, and 28.2% from sera. Dynamics analysis revealed that viral DNA was undetectable in most patients 20 days after symptom onset. IgM and IgG antibodies to MPXV were detected in all patients with 3–5 days earlier in the MPXV group than in the MPXV + HIV group.ConclusionThis cohort analysis based on a large outbreak among MSM in Guangzhou indicated no obvious differences in clinical symptoms, viral DNA data, but antibody responses were 3–5 days later in mpox patients with HIV infection.

Background and purpose: Gastric cancer is one of the most common malignant tumors in our country. The diagnosis and treatment process of gastric cancer lacks of sensitive and specific biomarker. This study aimed to explore the expression of plasma methylated Septin9 gene (mSEPT9) and its clinical significance in patients with gastric cancer. Methods: From April 2020 to November 2020, 221 patients with gastric cancer and 34 patients with no evidence of disease who visited Zhongshan Hospital Fudan University were enrolled. The status of mSEPT9 was detected by polymerase chain reaction (PCR) fluorescence probe method, and relative mSEPT9 value was determined by the ΔΔCt method. Detailed clinical data including pathological characteristics (patients characteristics and pathology characteristics) and serum biomarkers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA)12-5, CA19-9 and CA72-4] were collected and analyzed. Paired t test, χ2 test and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis. Results: The positive rate, sensitivity and specificity of plasma mSEPT9 were 35%, 35% and 100%, respectively in untreated patients with gastric cancer. The positive rate of mSEPT9 was higher in patients with blood vessel invasion, serosa invasion and lymphatic metastasis, which was 46.87% vs 12.50%, 45.16% vs 14.29%, 75.00% vs 40.00%, respectively (P

Objective: To identify the association between serum albumin levels and disease severity among adult patients with dengue in mainland China. Methods: This retrospective cohort study analyzed the data of adult patients (aged ≥ 18 years) hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in mainland China. Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue. Additionally, the association between serum albumin levels and severe dengue was evaluated using a generalized linear model [relative risks (RR)]. Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue. Results: Overall, 1568 patients were included in this study. Of these patients, 34 (2.17%) developed severe dengue. The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue (33 g/L vs. 37 g/L, P

Abstract Introduction The association between diabetes mellitus (DM) and risk of osteoarthritis (OA) is inconsistent based on published observational studies. This study aimed to conduct a two-sample Mendelian randomization (MR) analysis to explore the causal link between glycated hemoglobin (HbA1c) level and OA risk. Methods Genome-wide association studies (GWAS) summary statistics were obtained from the publicly available Integrative Epidemiology Unit (IEU) OpenGWAS database. A series of screening processes were performed to select qualified instrumental single-nucleotide polymorphisms (SNPs) strongly related to exposure. The inverse-variance-weighted method, weighted-median method, and MR–Egger method were performed to ensure robust and reliable results. The MR–Egger intercept test, Cochran’s Q test, and the leave-one-out sensitivity analysis were utilized to assess the horizontal pleiotropy, heterogeneities, and stability of these genetic variants for OA. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Results MR analyses found a robust causal association of genetically determined HbA1c with knee OA (OR = 1.561; 95% CI 1.110–2.197; P = 0.011), but not with hip OA (OR = 1.073; 95% CI 0.674–1.710; P = 0.766) or overall OA (OR = 1.141; 95% CI 0.904–1.441; P = 0.804). Sensitivity analyses showed that there was a strong association between SNPs and HbA1c (F = 21.138), no evidence of heterogeneity (Q = 150.625, P = 0.402), and no potential SNPs affecting the causal link. Conclusion Our MR study supported a causal effect of genetically increased HbA1c on knee OA risk.

ObjectiveTo compare and analyze the Ortho-Bridge System (OBS) clinical efficacy assisted by 3D printing and proximal femoral nail anti-rotation (PFNA) of AO/OTA type 31-A3 femoral intertrochanteric fractures in elderly patients.MethodsA retrospective analysis of 25 elderly patients diagnosed with AO/OTA type 31-A3 femoral intertrochanteric fracture was conducted from January 2020 to August 2022 at Yan’an Hospital, affiliated to Kunming Medical University. The patients were divided into 10 patients in the OBS group and 15 in the PFNA group according to different surgical methods. The OBS group reconstructed the bone models and designed the guide plate by computer before the operation, imported the data of the guide plate and bone models into a stereolithography apparatus (SLA) 3D printer, and printed them using photosensitive resin, thus obtaining the physical object, then simulating the operation and finally applying the guide plate to assist OBS to complete the operation; the PFNA group was treated by proximal femoral nail anti-rotation. The operation time, the intraoperative blood loss, Harris hip score (HHS), Oxford Hip Score (OHS), and complications were compared between the two groups.ResultsThe operation time and the intraoperative blood loss in the PFNA group were less than that in the OBS group, and there was a significant difference between the two groups (P < 0.05). The HHS during the 6th month using OBS was statistically higher than PFNA (P < 0.05), however, there were no significant differences in OHS during the 6th month between the OBS group and PFNA group (P > 0.05). The HHS and OHS during the 12th month in the OBS group were statistically better than in the PFNA group (P < 0.05).ConclusionThe OBS assisted by 3D printing and PFNA are effective measures for treating intertrochanteric fractures. Prior to making any decisions regarding internal fixation, it is crucial to evaluate the distinct circumstances of each patient thoroughly.

M-type stars are crucial for stellar activity studies because they cover two types of magnetic dynamos and are particularly intriguing for habitability studies due to their abundance and long lifespans during the main-sequence stage. In this paper, we used the LAMOST DR9 catalog and the GALEX UV archive data to investigate the chromospheric and UV activities of M-type stars. All the chromospheric and UV activity indices clearly show that the saturated and unsaturated regimes, and the well-known activity–rotation relation, are consistent with previous studies. Both the FUV and NUV activity indices exhibit a single-peaked distribution, while the H α and Ca ii H&K indices show a distinct double-peaked distribution. The gap between these peaks suggests a rapid transition from a saturated population to an unsaturated one. The smoothly varying distributions of different subtypes suggest a rotation-dependent dynamo for both early-type (partly convective) to late-type (fully convective) M stars. We identified a group of stars with high UV activity above the saturation regime (log ${R}_{\mathrm{NUV}}^{{\prime} }\gt -2.5$ ) but low chromospheric activity, and the underlying reason is unknown. By calculating the continuously habitable zone and the UV habitable zone for each star, we found that about 70% stars in the total sample and 40% stars within 100 pc are located in the overlapping region of these two habitable zones, indicating that a number of M stars are potentially habitable. Finally, we examined the possibility of UV activity studies of M stars using the China Space Station Telescope.

IntroductionAdipoR1 and AdipoR2 proteins, encoded by ADIPOR1 and ADIPOR2 genes respectively, are the receptors of adiponectin secrected by adipose tissue. Increasing studies have identified the vital role of adipose tissue in various diseases, including cancers. Hence, there is an urgent need to explore the roles of AdipoR1 and AdipoR2 in cancers.MethodsWe conducted a comprehensive pan-cancer analysis for the roles of AdipoR1 and AdipoR2 via several public databases, including expression differences, prognostic value, and the correlations with tumor microenvironment, epigenetic modification, and drug sensitivity.ResultsBoth ADIPOR1 and ADIPOR2 genes are dysregulated in most cancers, but their genomic alteration frequencies are low. In addition, they are also correlated with the prognosis of some cancers. Although they are not strongly correlated with tumor mutation burden (TMB) or microsatellite instability (MSI), ADIPOR1/2 genes display a significant association with cancer stemness, tumor immune microenvironment, immune checkpoint genes (especially CD274 and NRP1), and drug sensitivity.DiscussionADIPOR1 and ADIPOR2 play critical roles in diverse cancers, and it is a potential strategy to treat tumors through targeting ADIPOR1 and ADIPOR2.

Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus (DENV). DENV causes a febrile illness, severe forms including hemorrhagic fevers and shock with fatalities in humans. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 strains from Guangdong, China, have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo. A total of 22 patients tested to be DENV-2 positive and were enrolled in this study, 22 complete genomes were obtained by virus isolation and high-throughput sequencing. Phylogenetic and single amino polymorphism (SAP) analysis indicated that two major subgenotypes (A and C) of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018. The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains, including endemic genotype and imported genotype. It alerted the risk of cross-border transmission of DENV. A significant difference in replication rate was observed in C6/36 between different DENV-2 strains, although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles. DENV-2 subgenotypes (A and C) replicated efficiently in IFNAR−/− C57BL/6 mice, and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group. DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo, indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.

Objective: The goal of this study was to create a risk model based on the ferroptosis gene set that affects lung adenocarcinoma (LUAD) patients’ prognosis and to investigate the potential underlying mechanisms.Material and Methods: A cohort of 482 LUAD patients from the TCGA database was used to develop the prognostic model. We picked the module genes from the ferroptosis gene set using weighted genes co-expression network analysis (WGCNA). The least absolute shrinkage and selection operator (LASSO) and univariate cox regression were used to screen the hub genes. Finally, the multivariate Cox analysis constructed a risk prediction score model. Three other cohorts of LUAD patients from the GEO database were included to validate the prediction ability of our model. Furthermore, the differentially expressed genes (DEG), immune infiltration, and drug sensitivity were analyzed.Results: An eight-gene-based prognostic model, including PIR, PEBP1, PPP1R13L, CA9, GLS2, DECR1, OTUB1, and YWHAE, was built. The patients from the TCGA database were classified into the high-RS and low-RS groups. The high-RS group was characterized by poor overall survival (OS) and less immune infiltration. Based on clinical traits, we separated the patients into various subgroups, and RS had remarkable prediction performance in each subgroup. The RS distribution analysis demonstrated that the RS was significantly associated with the stage of the LUAD patients. According to the study of immune cell infiltration in both groups, patients in the high-RS group had a lower abundance of immune cells, and less infiltration was associated with worse survival. Besides, we discovered that the high-RS group might not respond well to immune checkpoint inhibitors when we analyzed the gene expression of immune checkpoints. However, drug sensitivity analysis suggested that high-RS groups were more sensitive to common LUAD agents such as Afatinib, Erlotinib, Gefitinib, and Osimertinib.Conclusion: We constructed a novel and reliable ferroptosis-related model for LUAD patients, which was associated with prognosis, immune cell infiltration, and drug sensitivity, aiming to shed new light on the cancer biology and precision medicine.

Diploid potatoes are typically self-incompatible, complicating efforts to breed diploid cultivars. Here the authors report map-based cloning of the S-locus inhibitor (Sli) gene in potato which encodes a non S-locus F-box protein that is expressed in pollen and can functions like a general S-RNase inhibitor to overcome self-incompatibility.

Abstract Novel Coronavirus disease 2019 (COVID‐19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID‐19 patients hospitalized in 23 centers affiliated to Hubei COVID‐19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID‐19 infection (p = 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts (p values were 0.033,

To figure out the molecular mechanism in the esophageal squamous carcinoma (ESCC) with the discrepancy in the tissue-resident microbiota, we selected clinical features, RNA sequences, and transcriptomes of ESCC patients from The Cancer Genome Atlas (TCGA) website and detailed tissue-resident microbiota information from The Cancer Microbiome Atlas (n = 60) and explored the infiltration condition of particular microbiota in each sample. We classified the tissue-resident micro-environment of ESCC into two clusters (A and B) and built a predictive classifier model. Cluster A has a higher proportion of certain tissue-resident microbiota with comparatively better survival, while Cluster B has a lower proportion of certain tissue-resident microbiota with comparatively worse survival. We showed traits of gene and clinicopathology in the esophageal tissue-resident micro-environment (ETM) phenotypes. By comparing the two clusters’ molecular signatures, we find that the two clusters have obvious differences in gene expression and mutation, which lead to pathway expression discrepancy. Several pathways are closely related to tumorigenesis. Our results may demonstrate a synthesis of the infiltration pattern of the esophageal tissue-resident micro-environment in ESCC. We reveal the mechanism of esophageal tissue-resident microbiota discrepancy in ESCC, which may contribute to therapy progress for patients with ESCC.

Objective Computerised clinical decision support systems (CDSS) are an increasingly important part of nurse and allied health professional (AHP) roles in delivering healthcare. The impact of these technologies on these health professionals’ performance and patient outcomes has not been systematically reviewed. We aimed to conduct a systematic review to investigate this.Materials and methods The following bibliographic databases and grey literature sources were searched by an experienced Information Professional for published and unpublished research from inception to February 2021 without language restrictions: MEDLINE (Ovid), Embase Classic+Embase (Ovid), PsycINFO (Ovid), HMIC (Ovid), AMED (Allied and Complementary Medicine) (Ovid), CINAHL (EBSCO), Cochrane Central Register of Controlled Trials (Wiley), Cochrane Database of Systematic Reviews (Wiley), Social Sciences Citation Index Expanded (Clarivate), ProQuest Dissertations & Theses Abstracts & Index, ProQuest ASSIA (Applied Social Science Index and Abstract), Clinical Trials.gov, WHO International Clinical Trials Registry (ICTRP), Health Services Research Projects in Progress (HSRProj), OpenClinical(www.OpenClinical.org), OpenGrey (www.opengrey.eu), Health.IT.gov, Agency for Healthcare Research and Quality (www.ahrq.gov). Any comparative research studies comparing CDSS with usual care were eligible for inclusion.Results A total of 36 106 non-duplicate records were identified. Of 35 included studies: 28 were randomised trials, three controlled-before-and-after studies, three interrupted-time-series and one non-randomised trial. There were ~1318 health professionals and ~67 595 patient participants in the studies. Most studies focused on nurse decision-makers (71%) or paramedics (5.7%). CDSS as a standalone Personal Computer/LAPTOP-technology was a feature of 88.7% of the studies; only 8.6% of the studies involved ‘smart’ mobile/handheld-technology.Discussion CDSS impacted 38% of the outcome measures used positively. Care processes were better in 47% of the measures adopted; examples included, nurses’ adherence to hand disinfection guidance, insulin dosing, on-time blood sampling and documenting care. Patient care outcomes in 40.7% of indicators were better; examples included, lower numbers of falls and pressure ulcers, better glycaemic control, screening of malnutrition and obesity and triaging appropriateness.Conclusion CDSS may have a positive impact on selected aspects of nurses’ and AHPs’ performance and care outcomes. However, comparative research is generally low quality, with a wide range of heterogeneous outcomes. After more than 13 years of synthesised research into CDSS in healthcare professions other than medicine, the need for better quality evaluative research remains as pressing.

The concentration of chlorogenic acids (CGAs), is tightly associated with the appearance, taste, and nutrient content of potato tubers. Manipulation of tuber CGA concentrations allows for the breeding of quality traits in potatoes. Currently, a hybrid potato breeding system that aims to convert tetraploid potato into a diploid seed crop represents a new development in potato breeding. Unfortunately, however, a systematic study of CGA formation is very limited in diploid potatoes. Here, using a diverse panel of diploid potatoes, including 40 ancestors and 374 landraces, we analyzed the influence of location, environment, genetic basis, as well as expression of enzymes, in affecting the CGA concentrations in diploid lines. We revealed a selection of the decreased CGA level of tuber flesh in the domestication of diploid potatoes. Moreover, we identified 18 SNPs associated with tuber CGA levels using re-sequenced genome data. This study provides a basis for the breeding of high-quality potato by taking into consideration customer preferences.

Abstract Background Pre-operative risk scores are more valuable than post-procedure risk scores because of lacking effective treatment for contrast-induced acute kidney injury (CI-AKI). A number of pre-operative risk scores have been developed, but due to lack of effective external validation, most of them are also difficult to apply accurately in clinical practice. It is necessary to review and validate the published pre-operative risk scores for CI-AKI. Materials and methods We systematically searched PubMed and EMBASE databases for studies of CI-AKI pre-operative risk scores and assessed their calibration and discriminatory in a cohort of 2669 patients undergoing coronary angiography or percutaneous coronary intervention (PCI) from September 2007 to July 2017. The definitions of CI-AKI may affect the validation results, so three definition were included in this study, CI-AKI broad1 was defined as an increase in serum creatinine (Scr) of 44.2 μmol/L or 25%; CI-AKI broad2, an increase in Scr of 44.2 μmol/L or 50%; and CI-AKI-narrow, an increase in Scr of 44.2 μmol/L. The calibration of the model was assessed with the Hosmer-Lemeshow test and the discriminatory capacity was identified by C-statistic. Results Of the 8 pre-operative risk scores for CI-AKI identified, 7 were single-center study and only 1 was based on multi-center study. In addition, 7 of the scores were just validated internally and only Chen score was externally validated. In the validation cohort of 2669 patients, the incidence of CI-AKI ranged from 3.0%(Liu) to 16.4%(Chen) for these scores. Furthermore, the incidence of CI-AKI was 6.59% (178) for CI-AKI broad1, 1.44% (39) for CI-AKI broad2, and 0.67% (18) for CI-AKI-narrow. For CI-AKI broads, C-statistics varied from 0.44 to 0.57. For CI-AKI-narrow, the Maioli score had the best discrimination and calibration, what’s more, the C-statistics of Maioli, Chen, Liu and Ghani was ≥0.7. Conclusion Most pre-operative risk scores were established based on single-center studies and most of them lacked external validation. For CI-AKI broads, the prediction accuracy of all risk scores was low. The Maioli score had the best discrimination and calibration, when using the CI-AKI-narrow definition.

Abstract Background Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. Methods Our objective was to estimate the effect of LDCT lung cancer screening on mortality in high-risk populations. A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (such as chest X-ray (CXR)) was conducted. RCTs of CXR screening were additionally included in the network meta-analysis. Bibliographic sources including MEDLINE, Embase, Web of Science and the Cochrane Library were searched to January 2017. All key review steps were done by two persons. Quality assessment used the Cochrane Risk of Bias tool. Meta-analyses were performed. Results Four RCTs were included. More will provide data in the future. Meta-analysis demonstrated that LDCT screening with up to 9.80 years of follow-up was associated with a statistically non-significant decrease in lung cancer mortality (pooled relative risk (RR) 0.94, 95% confidence interval (CI) 0.74 to 1.19; p = 0.62). There was a statistically non-significant increase in all-cause mortality. Given the considerable heterogeneity for both outcomes, the results should be treated with caution. Network meta-analysis including the four original RCTs plus two further RCTs assessed the relative effectiveness of LDCT, CXR and usual care. The results showed that in terms of lung cancer mortality reduction LDCT was ranked as the best screening strategy, CXR screening as the worst strategy and usual care intermediate. Conclusions LDCT screening may be effective in reducing lung cancer mortality but there is considerable uncertainty: the largest of the RCTs compared LDCT with CXR screening rather than no screening; there is imprecision of the estimates; and there is important heterogeneity between the included study results. The uncertainty about the effect on all-cause mortality is even greater. Maturing trials may resolve the uncertainty.

Objectives Diabetic macular edema (DME) is a complication of diabetes mellitus that leads to diabetic retinopathy. Thus far, the role of serum exosomal microRNAs (miRNAs) in DME progression remains elusive. This study investigated serum exosomal miRNAs from patients with type 2 diabetes (T2D) and DME to identify miRNAs associated with expression of vascular endothelial growth factor (VEGF), a pivotal component in DME progression; it also evaluated the diagnostic values of these miRNAs for DME. Methods Serum was collected from patients with T2D who did (n = 20) and did not have DME (n = 24). Exosomes were isolated from serum and subjected to real-time polymerase chain reaction, western blotting, luciferase reporter, and miRNA profiling analyses. Results VEGF was significantly upregulated in ARPE-19 cells treated with exosomes from patients with T2D and DME, compared with exosomes from patients with T2D alone. Among the top 10 downregulated miRNAs identified during exosomal miRNA profiling, miR-377-3p inhibited the expression of VEGF. Luciferase reporter assays confirmed that miR-377-3p could directly regulate VEGF expression. Receiver operating characteristic analysis identified serum exosomal miR-377-3p as a potential biomarker for DME. Conclusion Serum exosomal miR-377-3p inhibits VEGF expression to suppress retinal pigment epithelium proliferation and offers a diagnostic biomarker for DME.

Background: Rheumatoid arthritis is a chronic autoimmune disease that primarily causes inflammation, pain and stiffness in the joints. People with severe disease may be treated with biological disease-modifying anti-rheumatic drugs, including tumour necrosis factor-α inhibitors, but the efficacy of these drugs is hampered by the presence of anti-drug antibodies. Monitoring the response to these treatments typically involves clinical assessment using response criteria, such as Disease Activity Score in 28 joints or European League Against Rheumatism. Enzyme-linked immunosorbent assays can also be used to measure drug and antibody levels in the blood. These tests may inform whether or not adjustments to treatment are required or help clinicians to understand the reasons for treatment non-response or a loss of response. Methods: Systematic reviews were conducted to identify studies reporting on the clinical effectiveness and cost-effectiveness of using enzyme-linked immunosorbent assays to measure drug and anti-drug antibody levels to monitor the response to tumour necrosis factor-α inhibitors [adalimumab (Humira®; AbbVie, Inc., North Chicago, IL, USA), etanercept (Enbrel®; Pfizer, Inc., New York, NY, USA), infliximab (Remicade®, Merck Sharp & Dohme Limited, Hoddesdon, UK), certolizumab pegol (Cimzia®; UCB Pharma Limited, Slough, UK) and golimumab (Simponi®; Merck Sharp & Dohme Limited)] in people with rheumatoid arthritis who had either achieved treatment target (remission or low disease activity) or shown primary or secondary non-response to treatment. A range of bibliographic databases, including MEDLINE, EMBASE and CENTRAL (Cochrane Central Register of Controlled Trials), were searched from inception to November 2018. The risk of bias was assessed using the Cochrane ROBINS-1 (Risk Of Bias In Non-randomised Studies – of Interventions) tool for non-randomised studies, with adaptations as appropriate. Threshold and cost–utility analyses that were based on a decision tree model were conducted to estimate the economic outcomes of adding therapeutic drug monitoring to standard care. The costs and resource use were considered from the perspective of the NHS and Personal Social Services. No discounting was applied to the costs and effects owing to the short-term time horizon of 18 months that was adopted in the economic analysis. The impact on the results of variations in testing and treatment strategies was explored in numerous clinically plausible sensitivity analyses. Results: Two studies were identified: (1) a non-randomised controlled trial, INGEBIO, that compared standard care with therapeutic drug monitoring using Promonitor® assays [Progenika Biopharma SA (a Grifols–Progenika company), Derio, Spain] in Spanish patients receiving adalimumab who had achieved remission or low disease activity; and (2) a historical control study. The economic analyses were informed by INGEBIO. Different outcomes from INGEBIO produced inconsistent results in both threshold and cost–utility analyses. The cost-effectiveness of therapeutic drug monitoring varied, from the intervention being dominant to the incremental cost-effectiveness ratio of £164,009 per quality-adjusted life-year gained. However, when the frequency of testing was assumed to be once per year and the cost of phlebotomy appointments was excluded, therapeutic drug monitoring dominated standard care. Limitations: There is limited relevant research evidence and much uncertainty about the clinical effectiveness and cost-effectiveness of using enzyme-linked immunosorbent assay-based testing for therapeutic drug monitoring in rheumatoid arthritis patients. INGEBIO had serious limitations in relation to the National Institute for Health and Care Excellence scope: only one-third of participants had rheumatoid arthritis, the analyses were mostly not by intention to treat and the follow-up was 18 months only. Moreover, the outcomes might not be generalisable to the NHS. Conclusions: Based on the available evidence, no firm conclusions could be made about the cost-effectiveness of therapeutic drug monitoring in England and Wales. Future work: Further controlled trials are required to assess the impact of using enzyme-linked immunosorbent assays for monitoring the anti-tumour necrosis factors in people with rheumatoid arthritis. Study registration: This study is registered as PROSPERO CRD42018105195. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 8. See the NIHR Journals Library website for further project information.

Abstract Background High-throughput non-invasive prenatal testing (NIPT) for fetal Rhesus D (RhD) status could avoid unnecessary treatment with anti-D immunoglobulin for RhD-negative women found to be carrying an RhD-negative fetus. We aimed to assess the diagnostic accuracy of high-throughput NIPT for fetal RhD status in RhD-negative women not known to be sensitized to the RhD antigen, by performing a systematic review and meta-analysis. Methods Prospective cohort studies of high-throughput NIPT used to determine fetal RhD status were included. The eligible population were pregnant women who were RhD negative and not known to be sensitized to RhD antigen. The index test was high-throughput, NIPT cell-free fetal DNA tests of maternal plasma used to determine fetal RhD status. The reference standard considered was serologic cord blood testing at birth. Databases including MEDLINE, EMBASE, and Science Citation Index were searched up to February 2016. Two reviewers independently screened titles and abstracts and assessed full texts identified as potentially relevant. Risk of bias was assessed using QUADAS-2. The bivariate and hierarchical summary receiver-operating characteristic (HSROC) models were fitted to calculate summary estimates of sensitivity, specificity, false positive and false negative rates, and the associated 95% confidence intervals (CIs). Results A total of 3921 references records were identified through electronic searches. Eight studies were included in the systematic review. Six studies were judged to be at low risk of bias. The HSROC models demonstrated high diagnostic performance of high-throughput NIPT testing for women tested at or after 11 weeks gestation. In the primary analysis for diagnostic accuracy, women with an inconclusive test result were treated as having tested positive. The false negative rate (incorrectly classed as RhD negative) was 0.34% (95% CI 0.15 to 0.76) and the false positive rate (incorrectly classed as RhD positive) was 3.86% (95% CI 2.54 to 5.82). There was limited evidence for non-white women and multiple pregnancies. Conclusions High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin. The applicability of these findings to non-white women and women with multiple pregnancies is uncertain.

By using the LAMOST time-domain survey data, we study stellar activities based on the H _α lines for about 2000 stars in four K2 plates. Two indices, ${R}_{{\rm{H}}\alpha }^{{\prime} }$ and ${R}_{{\rm{H}}\alpha }^{+}$ , are computed from LAMOST spectra, the former of which is derived by excluding the photospheric contributions to the H _α lines, while the latter is derived by further subtracting the non-dynamo-driven chromospheric emission. Meanwhile, the periodicity and variation amplitudes are computed from K2 light curves. Both the ${R}_{{\rm{H}}\alpha }^{{\prime} }$ –Ro relation and ${R}_{{\rm{H}}\alpha }^{+}$ –Ro relation show complicated profiles in the nonsaturated decay region. Hot stars show flatter slopes and a higher activity level than cool stars, and the behavior is more notable in the ${R}_{{\rm{H}}\alpha }^{+}$ – R _o relation. This is consistent with recent studies using other activity proxies, including L _x / L _bol , ${R}_{\mathrm{HK}}^{{\prime} }$ , and amplitudes of optical light curves. This may suggest different kinds of stars follow different power laws in the decay region. Most of our targets have multiple observations, and some of them exhibit significant variability of H α emissions, which may cause the large scatters shown in the decay region. We find three targets exhibiting positive correlation in a rotational phase, possibly indicating that their optical light curves are dominated by hot faculae rather than cool starspots.

Background: Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. Objectives: To estimate the clinical effectiveness and cost-effectiveness of LDCT lung cancer screening in high-risk populations. Data sources: Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Methods: Clinical effectiveness – a systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programmes [such as chest X-ray (CXR)] was conducted. Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Meta-analyses, including network meta-analyses, were performed. Cost-effectiveness – an independent economic model employing discrete event simulation and using a natural history model calibrated to results from a large RCT was developed. There were 12 different population eligibility criteria and four intervention frequencies [(1) single screen, (2) triple screen, (3) annual screening and (4) biennial screening] and a no-screening control arm. Results: Clinical effectiveness – 12 RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT, with ≤ 9.80 years of follow-up, was associated with a non-statistically significant decrease in lung cancer mortality (pooled relative risk 0.94, 95% confidence interval 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increase in all-cause mortality. Given the considerable heterogeneity detected between studies for both outcomes, the results should be treated with caution. Network meta-analysis, including six RCTs, was performed to assess the relative clinical effectiveness of LDCT, CXR and usual care. The results showed that LDCT was ranked as the best screening strategy in terms of lung cancer mortality reduction. CXR had a 99.7% probability of being the worst intervention and usual care was ranked second. Cost-effectiveness – screening programmes are predicted to be more effective than no screening, reduce lung cancer mortality and result in more lung cancer diagnoses. Screening programmes also increase costs. Screening for lung cancer is unlikely to be cost-effective at a threshold of £20,000/quality-adjusted life-year (QALY), but may be cost-effective at a threshold of £30,000/QALY. The incremental cost-effectiveness ratio for a single screen in smokers aged 60–75 years with at least a 3% risk of lung cancer is £28,169 per QALY. Sensitivity and scenario analyses were conducted. Screening was only cost-effective at a threshold of £20,000/QALY in only a minority of analyses. Limitations: Clinical effectiveness – the largest of the included RCTs compared LDCT with CXR screening rather than no screening. Cost-effectiveness – a representative cost to the NHS of lung cancer has not been recently estimated according to key variables such as stage at diagnosis. Certain costs associated with running a screening programme have not been included. Conclusions: LDCT screening may be clinically effective in reducing lung cancer mortality, but there is considerable uncertainty. There is evidence that a single round of screening could be considered cost-effective at conventional thresholds, but there is significant uncertainty about the effect on costs and the magnitude of benefits. Future work: Clinical effectiveness and cost-effectiveness estimates should be updated with the anticipated results from several ongoing RCTs [particularly the NEderlands Leuvens Longkanker Screenings ONderzoek (NELSON) screening trial]. Study registration: This study is registered as PROSPERO CRD42016048530. Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: High-throughput non-invasive prenatal testing (NIPT) for fetal rhesus (D antigen) (RhD) status could avoid unnecessary treatment with routine anti-D immunoglobulin for RhD-negative women carrying a RhD-negative fetus, although this may lead to an increased risk of RhD sensitisations. Objectives: To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of high-throughput NIPT and to develop a cost-effectiveness model. Methods: We searched MEDLINE and other databases, from inception to February 2016, for studies of high-throughput NIPT free-cell fetal deoxyribonucleic acid (DNA) tests of maternal plasma to determine fetal RhD status in RhD-negative pregnant women who were not known to be sensitised to the RhD antigen. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and A Cochrane Risk of Bias Assessment Tool: for Non-Randomised Studies of Interventions (ACROBAT-NRSI). Summary estimates of false-positive rates (FPRs) and false-negative rates (FNRs) were calculated using bivariate models. Clinical effectiveness evidence was used to conduct a simulation study. We developed a de novo probabilistic decision tree-based cohort model that considered four alternative ways in which the results of NIPT could guide the use of anti-D immunoglobulin antenatally and post partum. Sensitivity analyses (SAs) were conducted to address key uncertainties and model assumptions. Results: Eight studies were included in the diagnostic accuracy review, seven studies were included in the clinical effectiveness review and 12 studies were included in the review of implementation. Meta-analyses included women mostly at or post 11 weeks’ gestation. The pooled FNR (women at risk of sensitisation) was 0.34% [95% confidence interval (CI) 0.15% to 0.76%] and the pooled FPR (women needlessly receiving anti-D) was 3.86% (95% CI 2.54% to 5.82%). SAs did not materially alter the overall results. Data on clinical outcomes, including sensitisation rates, were limited. Our simulation suggests that NIPT could substantially reduce unnecessary use of antenatal anti-D with only a small increase in the risk of sensitisation. All large implementation studies suggested that large-scale implementation of high-throughput NIPT was feasible. Seven cost-effectiveness studies were included in the review, which found that the potential for the use of NIPT to produce cost savings was dependent on the cost of the test. Our de novo model suggested that high-throughput NIPT is likely to be cost saving compared with the current practice of providing routine antenatal anti-D prophylaxis to all women who are RhD negative. The extent of the cost saving appeared to be sufficient to outweigh the small increase in sensitisations. However, the magnitude of the cost saving is highly sensitive to the cost of NIPT itself. Limitations: There was very limited evidence relating to the clinical effectiveness of high-throughput NIPT, with no evidence on potential adverse effects. The generalisability of the findings to non-white women and multiple pregnancies is unclear. Conclusions: High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women from 11 weeks’ gestation and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin, potentially resulting in cost savings of between £485,000 and £671,000 per 100,000 pregnancies if the cost of implementing NIPT is in line with that reflected in this evaluation. Future work: Further research on the diagnostic accuracy of NIPT in non-white women is needed. Study registration: This study is registered as PROSPERO CRD42015029497. Funding: The National Institute for Health Research Health Technology Assessment programme.

Elucidating the differences in gene expression profiles of plants with different ploidy levels and how they affect phenotypic traits is vital to allow genetic improvement of plants such as Ma bamboo (Dendrocalamus latiflorus Munro). We previously obtained triploid (2n = 3X = 36), hexaploid (2n = 6X = 72), and dodecaploid (2n = 12X = 144) Ma bamboo plants from embryogenic callus by anther culturing. Phenotypic differences between these plants appeared to be correlated with differences in ploidy. Here, we performed transcriptome profiling and sequencing of anther-regenerated plants and F1 seedlings of different ploidy levels using RNA-Seq technology. Pair-wise comparisons of the four resulting libraries revealed 8,396 differentially expressed genes. These differentially expressed genes were annotated, functionally classified, and partially validated. We found that the chromosome doubling led to substantially up- or down-regulation of genes that were involved in cell growth and differentiation; the polyploidy levels altered the anatomical, physiological and growth characteristics, such as leaf thickness, fusoid cell and stomatal size, shoot number, photosynthesis and respiration rate and so on. Additionally, two candidate genes, EXPB3 and TCP with potenitial regulatory roles in cell division and differentiation, were identified through gene coexpresseion network analysis. These results highlight the significance of potential applications of polyploidy, and provide valuable information for the genetic breeding of bamboo species.

Laser-machined microcavities for simultaneous measurement of high-temperature and high-pressure are demonstrated. These two cascaded microcavities are an air cavity and a composite cavity including a section of fiber and an air cavity. They are both placed into a pressure chamber inside a furnace to perform simultaneous pressure and high-temperature tests. The thermal and pressure coefficients of the short air cavity are ~0.0779 nm/°C and ~1.14 nm/MPa, respectively. The thermal and pressure coefficients of the composite cavity are ~32.3 nm/°C and ~24.4 nm/MPa, respectively. The sensor could be used to separate temperature and pressure due to their different thermal and pressure coefficients. The excellent feature of such a sensor head is that it can withstand high temperatures of up to 400 °C and achieve precise measurement of high-pressure under high temperature conditions.

Both bisphenol A (BPA, an endocrine disrupting chemicals) and genistein (a phytoestrogen mainly derived from leguminosae) are able to bind to estrogen receptors, but they are considered to have different effects on metabolic syndrome, surprisingly. We here investigate the effects of an environmentally relevant dose of BPA alone and the combined effects with genistein on lipid metabolism in rats. Eight groups of adult male Wistar rats, fed with either standard chow diet or high-fat diet, were treated with BPA (50μg/kg/day), genistein (10mg/kg/day), and BPA plus genistein for 35 weeks, respectively. Metabolic parameters in serum and liver were determined; the hematoxylin/eosin and oil Red O staining were used to observe liver histologically; gene expressions related to hepatic lipid metabolism were analyzed by Real-time PCR; protein expressions of PPARγ, PPARα and LC3 in liver were analyzed by western blotting. No difference of body weight gain, total energy intake, liver weight/body weight or body fat percentage in both STD- and HFD-fed sub-groups was observed after treatment with BPA, genistein, or BPA plus genistein (P>0.05). Genistein alleviated lipid metabolism disorder and decreased the mRNA and protein expression of PPARγ (P0.05) or combined with genistein. Our findings suggest that long-term environmentally relevant dose of BPA did not affect lipid metabolism, and had no synergetic or antagonistic roles on genistein's beneficial function on hepatic lipid metabolism.

Background: It is uncertain which simple measures of childhood obesity are best for predicting future obesity-related health problems and the persistence of obesity into adolescence and adulthood. Objectives: To investigate the ability of simple measures, such as body mass index (BMI), to predict the persistence of obesity from childhood into adulthood and to predict obesity-related adult morbidities. To investigate how accurately simple measures diagnose obesity in children, and how acceptable these measures are to children, carers and health professionals. Data sources: Multiple sources including MEDLINE, EMBASE and The Cochrane Library were searched from 2008 to 2013. Methods: Systematic reviews and a meta-analysis were carried out of large cohort studies on the association between childhood obesity and adult obesity; the association between childhood obesity and obesity-related morbidities in adulthood; and the diagnostic accuracy of simple childhood obesity measures. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and a modified version of the Quality in Prognosis Studies (QUIPS) tool. A systematic review and an elicitation exercise were conducted on the acceptability of the simple measures. Results: Thirty-seven studies (22 cohorts) were included in the review of prediction of adult morbidities. Twenty-three studies (16 cohorts) were included in the tracking review. All studies included BMI. There were very few studies of other measures. There was a strong positive association between high childhood BMI and adult obesity [odds ratio 5.21, 95% confidence interval (CI) 4.50 to 6.02]. A positive association was found between high childhood BMI and adult coronary heart disease, diabetes and a range of cancers, but not stroke or breast cancer. The predictive accuracy of childhood BMI to predict any adult morbidity was very low, with most morbidities occurring in adults who were of healthy weight in childhood. Predictive accuracy of childhood obesity was moderate for predicting adult obesity, with a sensitivity of 30% and a specificity of 98%. Persistence of obesity from adolescence to adulthood was high. Thirty-four studies were included in the diagnostic accuracy review. Most of the studies used the least reliable reference standard (dual-energy X-ray absorptiometry); only 24% of studies were of high quality. The sensitivity of BMI for diagnosing obesity and overweight varied considerably; specificity was less variable. Pooled sensitivity of BMI was 74% (95% CI 64.2% to 81.8%) and pooled specificity was 95% (95% CI 92.2% to 96.4%). The acceptability to children and their carers of BMI or other common simple measures was generally good. Limitations: Little evidence was available regarding childhood measures other than BMI. No individual-level analysis could be performed. Conclusions: Childhood BMI is not a good predictor of adult obesity or adult disease; the majority of obese adults were not obese as children and most obesity-related adult morbidity occurs in adults who had a healthy childhood weight. However, obesity (as measured using BMI) was found to persist from childhood to adulthood, with most obese adolescents also being obese in adulthood. BMI was found to be reasonably good for diagnosing obesity during childhood. There is no convincing evidence suggesting that any simple measure is better than BMI for diagnosing obesity in childhood or predicting adult obesity and morbidity. Further research on obesity measures other than BMI is needed to determine which is the best tool for diagnosing childhood obesity, and new cohort studies are needed to investigate the impact of contemporary childhood obesity on adult obesity and obesity-related morbidities. Study registration: This study is registered as PROSPERO CRD42013005711. Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within- and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established. Objectives: We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment. Data sources: We searched 12 electronic databases (including MEDLINE, EMBASE, The Cochrane Library and trials registries) without language restrictions from inception to March 2012. We hand-searched three relevant journals for the 12 months prior to May 2012, and websites of five test manufacturers and the US Food and Drug Administration (FDA). Reference lists of included studies and relevant reviews were also searched. Review methods: A systematic review of test accuracy, clinical utility, reliability and reproducibility, and cost-effectiveness of two formation and two resorption bone turnover markers, in patients being treated for osteoporosis with any of bisphosphonate [alendronate (Fosamax®, MSD), risedronate (Actonel®, Warner Chilcott Company), zolendronate (Zometa®, Novartis)], raloxifene (Evista®, Eli Lilly and Company Ltd), strontium ranelate (Protelos®, Servier Laboratories Ltd), denosumab (Prolia®, Amgen Ltd) or teriparatide (Forsteo®, Eli Lilly and Company Ltd), was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Given the breadth of the review question, a range of study designs and outcome measures were eligible. The development of a decision model was planned to determine the cost-effectiveness of bone turnover markers for informing changes in patient management if clinical effectiveness could be established. Results: Forty-two studies (70 publications) met the inclusion criteria; none evaluated cost-effectiveness. Only five were randomised controlled trials (RCTs); these assessed only the impact of bone marker monitoring on aspects of adherence. No RCTs evaluated the effectiveness of bone turnover marker monitoring on treatment management. One trial suggested that feedback of a good response decreased non-persistence [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.95], and feedback of a poor response increased non-persistence (HR 2.22, 95% CI 1.27 to 3.89); it is not clear whether or not the trial recruited a population representative of that seen in clinical practice. Thirty-three studies reported results of some assessment of test accuracy, mostly correlations between changes in bone turnover and bone mineral density. Only four studies reported on intra- or interpatient reliability and reproducibility in treated patients. Overall, the results were inconsistent and inconclusive, owing to considerable clinical heterogeneity across the studies and the generally small sample sizes. As clinical effectiveness of bone turnover monitoring could not be established, a decision-analytic model was not developed. Conclusions: There was insufficient evidence to inform the choice of which bone turnover marker to use in routine clinical practice to monitor osteoporosis treatment response. The research priority is to identify the most promising treatment–test combinations for evaluation in subsequent, methodologically sound, RCTs. In order to determine whether or not bone turnover marker monitoring improves treatment management decisions, and ultimately impacts on patient outcomes in terms of reduced incidence of fracture, RCTs are required. Given the large number of potential patient population–treatment–test combinations, the most promising combinations would initially need to be identified in order to ensure that any RCTs focus on evaluating those strategies. As a result, the research priority is to identify these promising combinations, by either conducting small variability studies or initiating a patient registry to collect standardised data. Funding: The National Institute for Health Research Health Technology Assessment programme.