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Whole-genome genotyping methods are important for breeding. However, it has been challenging to develop a robust method for simultaneous foreground and background genotyping that can easily be adapted to different genes and species. In our study, we accidently discovered that in adapter ligation-mediated PCR, the amplification by primer-template mismatched annealing (PTMA) along the genome could generate thousands of stable PCR products. Based on this observation, we consequently developed a novel method for simultaneous foreground and background integrated genotyping by sequencing (FBI-seq) using one specific primer, wherein foreground genotyping is performed by primer-template perfect annealing (PTPA), while background genotyping employs PTMA. Unlike DNA arrays, multiple PCR, or genome target enrichments, FBI-seq requires little preliminary work for primer design and synthesis, and it is easily adaptable to different foreground genes and species. FBI-seq therefore provides a prolific, robust, and accurate method for simultaneous foreground and background genotyping to facilitate breeding in the post-genomics era. This article is protected by copyright. All rights reserved.

Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive impairment and abnormal mental behaviour. There is currently no effective cure. The development of early diagnostic markers and the mining of potential therapeutic targets are one of the important strategies. This study aimed to explore potential biomarkers or therapeutic targets related to AD in the hippocampus and prefrontal cortex, two brain regions highly related to AD. Differentially expressed genes and miRNAs between AD patients and healthy controls were obtained from the Gene Expression Omnibus database. The mRNA-miRNA network was constructed and key genes involved in AD were screened out by protein-protein interaction analysis, and were subsequently verified by independent datasets and qPCR in an AD mouse model. Our findings showed that six hub genes including CALN1, TRPM7, ATR, SOCS3, MOB3A and OGDH were believed to be involved in the pathogenesis of AD. Western blot analysis further determined that CALN1, ATR and OGDH were the possible biomarkers and therapeutic targets for AD. In addition, 6 possible miRNAs biomarkers have also been verified by qPCR on AD animal models. Our findings may benefit clinical diagnosis and early prevention of AD.

Phosphorus (P) is a macronutrient required for plant growth and reproduction. Orthophosphate (Pi), the preferred P form for plant uptake, is easily fixed in the soil, making it unavailable to plants. Limited phosphate rock resources, low phosphate fertilizer use efficiency and high demands for green agriculture production make it important to clarify the molecular mechanisms underlying plant responses to P deficiency and to improve plant phosphate efficiency in crops. Over the past 20 years, tremendous progress has been made in understanding the regulatory mechanisms of the plant P starvation response. Here, we systematically review current research on the mechanisms of Pi acquisition, transport and distribution from the rhizosphere to the shoot; Pi redistribution and reuse during reproductive growth; and the molecular mechanisms of arbuscular mycorrhizal symbiosis in rice (Oryza sativa L.) under Pi deficiency. Furthermore, we discuss several strategies for boosting P utilization efficiency and yield in rice.

Not all the susceptibility-guided therapies for Helicobacter pylori (H. pylori) infection achieve excellent eradication rates. The aim of this study was to perform a systematic review and meta-analysis to identify the optimal regimen for H. pylori treatment based on antibiotic susceptibility.A systematic search was performed in multiple databases. Studies reporting eradication rates of H. pylori with susceptibility-guided therapies were selected. Meta-analysis was conducted to calculate the pooled eradication rate among the treatment regimens.Forty-eight eligible studies with 101 susceptibility-guided treatment arms were included. The overall eradication rate in patients harboring susceptible strains was 95.0% (95% CI, 94.1-95.9%), but only 63.4% of treatment arms (64/101) achieved good eradication rates (≥ 90%). Pooled eradication rates in patients with susceptible strains were: 93.4% (95% CI, 92.0-94.8%) for clarithromycin, 99.0% (95% CI, 98.1-100%) for nitroimidazoles and 95.4% (95% CI, 93.6-97.2%) for fluoroquinolones. Among the arms using a triple therapy, 66.7% (28/42) using clarithromycin, 84.2% (16/19) using nitroimidazoles and 70.8% (17/24) using fluoroquinolones achieved good (≥ 90%) eradication rates. Of 13 arms using sequential therapy, ≥ 90% eradication was achieved in 14.3% (1/7) using clarithromycin, 25.0% (1/4) using nitroimidazoles and both arms (2/2) using fluoroquinolones.Susceptibility testing alone seemed insufficient to reliably attain high H. pylori cure rates. The eradication rate in patients with nitroimidazoles susceptible strains was higher than those of fluoroquinolones and clarithromycin.

To compare the effects of the adoption of lateral positions and lithotomy positions during the passive and active phases of the second stage of labour on perineal outcomes.An observational study with prospectively collected data, conducted in three hospitals in China.Attending midwives recorded the perineal outcomes and characteristics of women giving birth between July-November 2020. Binary logistic regression was performed to explore the effects of lateral positions on perineal outcomes during different phases of the second stage of labour. The STROBE guidelines guided the reporting of this study.Among primiparous women, when compared with those who adopted lateral positions during the passive phase of the second stage of labour and changed to lithotomy positions during the active phase, women who assumed lateral positions during both the passive and active phases had a higher rate of intact perineum/first-degree perineal tears and a reduced risk of episiotomy, and episiotomy/second-degree perineal tears. No significant difference was found in perineal outcomes between those who assumed lithotomy positions during the passive and active phases and those who adopted lateral positions during the passive phase and changed to lithotomy positions during the active phase. No significant difference was found in perineal outcomes among multiparous women, regardless of different positions adopted at the passive and/or the active phase.Lateral positions during the active phase may have protective effects on the perineum in primiparous women. However, adopting lateral positions only during the passive phase did not promote better perineal outcomes, regardless of parity.This study will provide a further reference for the use of lateral positions during different phases of the second stage of labour among primiparous and multiparous women in clinical practice, contributing to the perineal protection during childbirth.

To summarize the evidence on the effects of different techniques during the second stage of labour on reducing perineal laceration depending on available systematic reviews to provide optimal evidence for decision-making.Preventing perineal laceration has been considered an important part of improving women's health. Various techniques have been used to prevent perineal laceration during the second stage of labour. However, systematic reviews evaluating the effects of different techniques on reducing perineal laceration show inconsistent results.Overview of systematic reviews.Five English and four Chinese databases were systematically searched for relevant systematic reviews and meta-analyses published between 1 January 2016 and 31 August 2021. The quality of the included reviews was assessed by the AMSTAR 2 tool. A narrative synthesis was conducted to report the results of moderate-to-high quality systematic reviews. The overview was reported according to the PRISMA statement.Eighteen reviews were included, of which four reviews had moderate-to-high methodological quality. Perineal massage and warm compresses significantly decreased the incidence of third- or fourth-degree perineal laceration (moderate-quality evidence). Hands-off technique had no impact on perineal laceration (low-to-moderate quality evidence). Ritgen's manoeuvre could reduce the incidence of first-degree perineal laceration but increase the incidence of second-degree perineal laceration (very low-quality evidence). Spontaneous pushing (low-quality evidence) and delayed pushing (moderate-quality evidence) had no impact on the incidence of third- or fourth-degree perineal laceration. Upright positions did not increase the risk of third- or fourth-degree perineal laceration (very low- to low-quality evidence) but increased the risk of second-degree perineal laceration for women without epidural analgesia (low-quality evidence).Perineal massage and warm compresses could be the better choice for preventing perineal laceration in the second stage of labour.Midwives and obstetricians could use perineal massage and warm compresses to prevent perineal laceration and should consider women's preferences and experience with perineal techniques.

Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first‐line treatment of Chinese patients with advanced or recurrent non‐squamous non‐small cell lung cancer (NSCLC). Methods Stage IIIB‐IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4‐6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15th, 2017, and May 15th, 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th, 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1‐6) and median duration of treatment of 3.0 (range 0.0‐5.1) months. ORR of response‐evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80‐1.04, within the prespecified equivalence margin of 0.75‐1.33). Up to May 15th, 2020, with a median follow‐up of 13.6 (range 0.8‐28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1‐year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non‐squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non‐squamous NSCLC patients in the first‐line setting., This study demonstrated similarity between LY01008 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity in combination with paclitaxel and carboplatin as first‐line treatment in Chinese patients with advanced non‐squamous NSCLC.

The all-inorganic nature of CsPbI3 perovskites allows to enhance stability in perovskite devices. Research efforts have led to improved stability of the black phase in CsPbI3 films; however, these strategies-including strain and doping-are based on organic-ligand-capped perovskites, which prevent perovskites from forming the close-packed quantum dot (QD) solids necessary to achieve high charge and thermal transport. We developed an inorganic ligand exchange that leads to CsPbI3 QD films with superior phase stability and increased thermal transport. The atomic-ligand-exchanged QD films, once mechanically coupled, exhibit improved phase stability, and we link this to distributing strain across the film. Operando measurements of the temperature of the LEDs indicate that KI-exchanged QD films exhibit increased thermal transport compared to controls that rely on organic ligands. The LEDs exhibit a maximum EQE of 23 % with an electroluminescence emission centered at 640 nm (FWHM: ≈31 nm). These red LEDs provide an operating half-lifetime of 10 h (luminance of 200 cd m-2 ) and an operating stability that is 6× higher than that of control devices.

To evaluate and quantify the best available evidence regarding risk factors for severe perineal lacerations.Many studies have evaluated the risk factors for severe perineal lacerations. However, the results of those studies are inconsistent, and meta-analysis which thoroughly evaluates the risk factors for severe perineal lacerations is still lacking.Systematic review and meta-analysis of cohort studies based on the PRISMA guideline.PubMed, Embase, the Cochrane Library, CINAHL, ClinicalTrials.gov, CNKI, Wanfang Data, VIP and SinoMed were systematically searched for cohort studies reporting at least one risk factor for severe perineal lacerations from 1 January 2000 to 2 June 2021. Two reviewers independently conducted quality appraisal by NOS scale and extracted data. Data synthesis was conducted via RevMan 5.3 using a random-effects or fixed-effects model.A total of 47 studies with 7,043,218 women were included. The results showed that prior caesarean delivery (OR: 1.46, 95% CI 1.12-1.92) and pre-pregnant underweight (OR: 1.31, 95% CI 1.22-1.41) significantly increased the risk of severe perineal lacerations. The results also demonstrated that episiotomy was protective against severe perineal lacerations in forceps delivery (OR: 0.56, 95% CI 0.42-0.74), but not spontaneous vaginal delivery (OR: 1.30, 95% CI 0.81-2.07) or vacuum delivery (OR: 0.76, 95% CI 0.45-1.28). Nulliparity, foetus in occipitoposterior or occipitotransverse position, and midline episiotomy were also independent risk factors for severe perineal lacerations.Severe perineal lacerations are associated with many factors, and evidence-based risk assessment tools are needed to guide the midwives and obstetricians to estimate women's risk of severe perineal lacerations.This systematic review and meta-analysis identified some important risk factors for severe perineal lacerations, which provides comprehensive insights to guide the midwives to assess women's risk for severe perineal lacerations and take appropriate preventive measures to decrease the risk.

A nickel-catalyzed intramolecular coupling of thioesters and olefins has been developed for the efficient synthesis of spirocycles, a privileged scaffold commonly found in natural products. This transformation is characterized by the simultaneous transfer of both acyl and thiol moieties to the alkene, with the suppression of decarbonylation and β-hydrogen elimination. Initial mechanistic investigations are consistent with an oxidative addition/olefin insertion/reductive elimination mechanism. The incorporated methylene sulfide substituent can undergo a variety of further reactions to increase molecular diversity and complexity. These results demonstrate that thioester derivatives can be used as powerful building blocks for the assembly of complex scaffolds.

Population‐level identification of children and youth with ASD is essential for surveillance and planning for required services. The objective of this study was to develop and validate an algorithm for the identification of children and youth with ASD using administrative health data. In this retrospective validation study, we linked an electronic medical record (EMR)‐based reference standard, consisting 10,000 individuals aged 1–24 years, including 112 confirmed ASD cases to Ontario administrative health data, for the testing of multiple case‐finding algorithms. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and corresponding 95% confidence intervals (CI) were calculated for each algorithm. The optimal algorithm was validated in three external cohorts representing family practice, education, and specialized clinical settings. The optimal algorithm included an ASD diagnostic code for a single hospital discharge or emergency department visit or outpatient surgery, or three ASD physician billing codes in 3 years. This algorithm's sensitivity was 50.0% (95%CI 40.7–88.7%), specificity 99.6% (99.4–99.7), PPV 56.6% (46.8–66.3), and NPV 99.4% (99.3–99.6). The results of this study illustrate limitations and need for cautious interpretation when using administrative health data alone for the identification of children and youth with ASD. Lay Summary We tested algorithms (set of rules) to identify young people with ASD using routinely collected administrative health data. Even the best algorithm misses more than half of those in Ontario with ASD. To understand this better, we tested how well the algorithm worked in different settings (family practice, education, and specialized clinics). The identification of individuals with ASD at a population level is essential for planning for support services and the allocation of resources. Autism Res 2021, 14: 1037–1045. © 2021 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in north-western China, which has a high incidence of gastric cancer.Helicobacter pylori infection was analysed in 21 291 adults byThe infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR = 1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR = 1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR = 0.86, 95% CI: 0.83-0.90), individuals with high income (OR = 0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR = 0.93, 95% CI: 0.87-0.99) and individuals who consumed more fruit and vegetables (OR = 0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension and asthma were negatively correlated with H. pylori infection (P 0.05).The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetables, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extragastric diseases.Evaluer la prévalence de l'infection à Helicobacter pylori et les facteurs de risque et déterminer le sérotype des souches à Wuwei, situé dans le nord-ouest de la Chine, où l'incidence du cancer gastrique est élevée. MÉTHODES: L'infection à H. pylori a été analysée chez 21.291 adultes par un test respiratoire à l'urée auLa prévalence de l'infection à H. pylori est élevée à Wuwei. La principale souche répandue est du type I. L'âge, l'éducation, la profession, le revenu du ménage, la consommation de fruits et de légumes et l'habitude de manger rapidement sont des facteurs de risque indépendants d'infection à H. pylori, qui est également associée à des personnes ayant des antécédents de maladies extra-gastriques.

Highly selective divergent coupling reactions of benzocyclobutenones and indoles, in which the chemoselectivity is controlled by catalysts, are reported herein. The substrates undergo C2(indole)-C8(benzocyclobutenone) coupling to produce benzylated indoles and benzo[b]carbazoles in the Ni- and Ru-catalyzed reactions. A completely different selectivity pattern C2(indole)-C2(benzocyclobutenone) coupling to form arylated indoles is observed in the Rh-catalyzed reaction. Preliminary mechanistic studies suggest C-H and C-C activations in the reaction pathway. Synthetic utility of this protocol is demonstrated by the selective synthesis of three different types of carbazoles from the representative products.

Background and aims Three to 10 minutes of smoking cessation advice by physicians is effective to increase quit rates, but is not routinely practised. We examined the effectiveness of physicians' very brief (approximately 30 sec) smoking cessation intervention on quit rates among Chinese outpatient smokers. Design A pragmatic, open-label, individually randomized controlled trial. Setting Seventy-two medical outpatient departments of hospitals and/or community health centers in Guangdong, China. Participants Chinese adults who were daily cigarette smokers (n = 13 671, 99% males) were invited by their physician to participate during outpatient consultation. Smokers who were receiving smoking cessation treatment or were judged to need specialist treatment for cessation were excluded. Interventions The intervention group (n = 7015) received a 30-sec intervention including physician's very brief advice, a leaflet with graphic warnings and a card with contact information of available cessation services. The control group (n = 6656) received a very brief intervention on consuming vegetables and fruit. A total of 3466 participants in the intervention group were further randomized to receive a brief booster advice from trained study personnel via telephone 1 month following their doctor visit. Measurements The primary outcome was self-reported 7-day point prevalence abstinence (PPA) in the intervention and control groups at the 12-month follow-up. Secondary outcomes included self-reported 30-day abstinence and biochemically validated abstinence at 12-month follow-up. Findings By intention-to-treat, the intervention (versus control) group had greater self-reported 7-day abstinence [9.1 versus 7.8%, odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.03-1.26, P = 0.008] and 30-day abstinence (8.0 versus 6.9%, OR = 1.14, 95% CI = 1.03-1.27, P = 0.01) at 12-month follow-up. The effect size increased when only participants who received the intervention from compliant physicians were included (7-day PPA, OR = 1.42, 95% CI = 1.11-1.74). The group difference in biochemically validated abstinence was small (0.8 versus 0.8%, OR = 1.00, 95% CI = 0.71-1.42, P = 0.99). Conclusion A 30-sec smoking cessation intervention increased self-reported abstinence among mainly male smokers in China at 12-month follow-up (risk difference = 1.3%), and should be feasible to provide in most settings and delivered by all health-care professionals.

To assess the effects of upright positions on maternal outcomes for women without epidural analgesia in comparison with recumbent positions during the second stage of labour.Upright positions have many physiological advantages. The underlying benefits and risks of upright positions during the second stage of labour have been reported in many studies but the results are divergent.A meta-analysis of randomized controlled trials.The Cochrane Library, PubMed, Embase, CINAHL and ProQuest databases were systematically searched from inception to 17 June 2019.We conducted the quality appraisal using the Cochrane Collaboration's tool and performed meta-analyses using the Review Manager 5.3 software. The primary outcomes were instrumental vaginal delivery and the duration of the second stage of labour.Overall, 12 studies including 4,314 women were included. Upright positions significantly decreased the rate of instrumental vaginal delivery (risk ratio [RR] = 0.74, 95% CI 0.59-0.93), shortened the active pushing phase (mean difference [MD] = -8.16 min, 95% CI -16.29 to -0.02), decreased the rate of severe perineal trauma (RR = 0.35, 95% CI 0.14-0.87) and episiotomy (RR = 0.52, 95% CI 0.29-0.92), but significantly increased the rate of second-degree perineal trauma (RR = 1.45, 95% CI 1.10-1.90). However, there was no significant difference in the duration of the second stage of labour or postpartum haemorrhage.Upright positions are beneficial for improving maternal outcomes. Several results should be considered with caution. Researchers need to clarify the definition of upright positions and conduct large, robust studies in the future to provide stronger evidence.This meta-analysis explores a crucial issue in intrapartum care and clarifies the benefits and possible risks of upright positions in the second stage of labour. Midwives and obstetricians are encouraged to apply upright positions depending on women's preferences and labour progress but should take measures to prevent perineal trauma.目的: 评估在第二产程中,与卧位相比,直立体位对未使用硬膜外镇痛的产妇的预后的影响。 背景: 从生理角度讲,直立体位具有许多优势。许多研究报告了第二产程期间直立体位的基本益处和风险,但结果却不尽相同。 设计: 随机对照试验的荟萃分析。 数据来源: 从各数据库成立至2019年6月17日,对Cochrane Library、PubMed、Embase、CINAHL和ProQuest等数据库进行了系统化检索。 审查方法: 使用科克伦协作网的工具进行质量评价,并使用Review Manager 5.3软件进行荟萃分析。主要预后指标是器械性阴道分娩和第二产程的持续时间。 结果: 总的来说,包括了12项研究,涉及4314名妇女。直立体位显著降低了器械性阴道分娩率(风险比[RR]=0.74,95%置信区间0.59-0.93),缩短了主动推宫阶段(平均差 [MD]=−8.16分钟, 95%置信区间−16.29 to −0.02),降低了严重会阴创伤发生率(RR=0.35, 95%置信区间0.14-0.87)和会阴切开术(RR=0.52, 95%置信区间0.29-0.92),但显著增加了二度会阴创伤的发生率(RR=1.45, 95%置信区间.10-1.90)。但在第二产程的持续时间或产后出血方面没有显著差异。 结论: 直立位有利于改善孕产妇预后。有几项结果应予以谨慎考虑。研究人员需要明确直立体位的定义,并在未来进行大规模、稳健的研究,以提供更有力的证据。 影响: 本荟萃分析探讨了产时护理中的一个关键问题,并阐明了直立体位在第二产程中的益处和可能存在的风险。鼓励助产士和产科医生根据产妇的喜好和产程进展采用直立体位,但应采取措施防止会阴创伤。.

Amoxicillin and proton pump inhibitor dual Helicobacter pylori therapy has proved not to be reliably highly effective primarily because of traditional proton pump inhibitors' inability to maintain a high intragastric pH. Clarithromycin and proton pump inhibitor H. pylori dual therapy failed in part because clarithromycin resistance emerged during therapy causing treatment failures. The combination of amoxicillin, clarithromycin, and proton pump inhibitor was subsequently undermined by increasing clarithromycin resistance. Although vonoprazan appeared to restore the effectiveness of triple therapy, the improvement was almost entirely to improved effectiveness of amoxicillin dual therapy component and resulted in the majority (>85% currently in Japan) of those receiving vonoprazan-amoxicillin plus a second antibiotic (e.g. clarithromycin, metronidazole, fluoroquinolone, or rifabutin) receiving no benefit from the second antibiotic. The results in somewhere between 2800 and 5600 kg of unnecessary clarithromycin per one million H. pylori treatment courses per year in Japan. The only contribution of the second antibiotic is to increase global antimicrobial resistance. There are now sufficient data to prove that optimized vonoprazan-amoxicillin dual therapy can reliably achieve cure rates ≥95%. This manuscript discusses use of the principles of antimicrobial stewardship to develop potassium-competitive acid blocker-containing H. pylori therapies that will reliably achieve high H. pylori cure rates with minimal or no use of excess antibiotics. Such therapies are urgently needed so that use of vonoprazan triple therapies can be curtailed while also improving overall H. pylori cure rates.

Cartilaginous metaplasia is rare in primary central nervous system (CNS) neoplasms and has not been described in the histone 3 (H3) gene (H3) with a substitution of lysine to methionine (H3 K27M mutant) diffuse midline glioma before. Here, we report a case of H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia in a 56-year-old woman. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion located in the medulla oblongata and extended superiorly into the fourth ventricle. The tumor was macroscopically completely resected. Histologically, the tumor was composed of a gliomatous component and a well-differentiated cartilaginous component. Microvascular proliferation and necrosis were noted. According to immunohistochemical staining, glial cells were diffusely and strongly positive for glial fibrillary acidic protein (GFAP), oligodendrocyte lineage transcription factor 2 (Olig2), H3 K27M, and S-100 protein but negative for H3K27me3. The chondrocytes also were positive for GFAP and S-100 protein. The H3 K27M mutation was confirmed by sequencing in both the gliomatous and cartilaginous components, suggesting a common origin from the same progenitor cells. Based on these findings, the tumor was diagnosed as a diffuse midline glioma with H3 K27M mutation with widespread cartilaginous metaplasia, corresponding to WHO grade IV. This is an extremely rare H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia, and reporting this unusual case adds to the understanding of this tumor type.

CX-072 is an anti-PD-L1 (programmed death ligand 1) Probody therapeutic (Pb-Tx) designed to be preferentially activated by proteases in the tumor microenvironment and not in healthy tissue. Here, we report the model-informed drug development of CX-072. A quantitative systems pharmacology (QSP) model that captured known mechanisms of Pb-Tx activation, biodistribution, elimination, and target engagement was used to inform clinical translation. The QSP model predicted that a trough level of masked CX-072 (intact CX-072) of 13-99 nM would correspond to a targeted, 95% receptor occupancy in the tumor. The QSP model predictions appeared consistent with preliminary human single-dose pharmacokinetic (PK) data following CX-072 0.03-30.0 mg/kg as monotherapy: CX-072 circulated predominantly as intact CX-072 with minimal evidence of target-mediated drug disposition. A preliminary population PK (POPPK) analysis based upon 130 subjects receiving 0.03-30.0 mg/kg as monotherapy included a provision for a putative time-dependent and dose-dependent antidrug antibody (ADA) effect on clearance (CL) with a mixture model. Preliminary POPPK estimates for intact CX-072 time-invariant CL and volume of distribution were 0.306 L/day and 4.84 L, respectively. Exposure-response analyses did not identify statistically significant relationships with best change from baseline sum of measurements and either adverse events of grade ≥ 3 or of special interest. Simulations suggested that > 95% of patients receiving CX-072 10 mg/kg every two weeks would exceed the targeted trough level regardless of ADA, and that dose adjustment by body weight was not necessary, supporting a fixed 800 mg dose for evaluation in phase II.

Aims and objectives To assess the effects of flexible sacrum positions on mode of delivery, duration of the second stage of labour, perineal trauma, postpartum haemorrhage, maternal pain, abnormal foetal heart rate patterns and Apgar scores based on published literature. Background Maternal positions served as a nonmedical intervention may facilitate optimal maternal and neonatal outcomes during labour. Flexible sacrum positions are conducive to expanding pelvic outlet. Whether flexible sacrum positions have positive effects on maternal and neonatal well-being is a controversial issue under heated discussion. Design We performed a systematic review and meta-analysis based on PRISMA guidelines. Methods Randomised controlled trials (RCTs) comparing any flexible sacrum position with non-flexible sacrum position in the second stage of labour were included. PubMed, EMBASE, Cochrane Library, CINAHL, CNKI (China National Knowledge Infrastructure), SinoMed and Wanfang databases were searched from inception to 11 March 2019 for published RCTs. Risk of bias was assessed by the Cochrane criteria, and random-effects meta-analyses were conducted by RevMan 5.3. Results Sixteen studies (3,397 women) published in English were included. Flexible sacrum positions in the second stage of labour could reduce the incidence of operative delivery, instrumental vaginal delivery, caesarean section, episiotomy, severe perineal trauma, severe pain and shorten the duration of active pushing phase in the second stage of labour. However, flexible sacrum positions may increase the incidence of mild perineal trauma. There was no significant difference in the duration of the second stage of labour, maternal satisfaction and other outcomes. Conclusions Flexible sacrum positions are superior in promoting maternal well-being during childbirth. However, several results require careful interpretation. More rigorous original studies are needed to further explore their effects. Relevance to clinical practice The results support the use of flexible sacrum positions. Flexible sacrum positions are recommended to apply flexibly or tailor to individual woman's labour progress.

An acceptor-donor-acceptor (A-D-A)-type non-fullerene acceptor (NFA), PTTtID-Cl, featuring thieno[3,2-b]thieno[2''',3''':4'',5'']-pyrrolo[2'',3'':4',5']thieno[2',3':4,5]thieno-[2,3-d]pyrrole (DTPTt) as the electron-rich core and 2-(5,6-dichloro-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (ID-Cl) as the peripheral electron-deficient terminal group was synthesized and characterized. PTTtID-Cl exhibited strong absorption in the range of 700-850 nm in CHCl3 and redshifted absorption centered at 881 nm in a thin film. The near infrared (NIR)-absorption of PTTtID-Cl was combined with a low-bandgap polymer donor (PTB7-Th) to achieve binary and semitransparent organic photovoltaics (OPVs) with a power conversion efficiency (PCE) of 8.9 % and 7.7 % (with an average visible transmittance (AVT) of 16.7 %), respectively. A ternary device with a ratio of PM7/PTTtID-Cl/IT-4F=1:0.15:0.85 (w/w) achieved a short-circuit current density of 19.46 mA cm-2 , an open-circuit voltage of 0.87 V, and a fill factor of 71.2 %, giving a PCE of 12.0 %. In addition, by employing the Ag/ITO/Ag microcavity structure, semitransparent colorful binary organic photovoltaics (OPVs) with superior transparency of 27.9 % at 427 nm and 22.7 % at 536 nm for blue and green devices, respectively, were prepared. The semitransparent colorful devices based on the optimized ternary blend gave PCEs of 8.7 %, 8.4 %, and 9.1 % for blue, green, and red devices, respectively. These results indicate the promising potential of PTTtID-Cl as a NIR-absorption NFA for applications in semitransparent colorful binary and ternary OPVs.

Background Clinical practice guidelines on uncomplicated birth provide clinical practice guidance and help to reduce unnecessary, non-evidence-based and potentially harmful intrapartum care practices. Little is known about the trustworthiness and consistency of these guidelines. Objectives To appraise guidelines relevant to uncomplicated birth, and summarise consensus and non-consensus recommendations. Search strategy Eight literature databases and the websites of guideline development institutions and organisations of obstetricians, gynaecologists and midwives were searched from January 2008 to October 2018. Selection criteria Guidelines that: reported in Chinese or English; labelled guideline, or recommendation, or consensus, or practice parameter, or position paper/stand; with uncomplicated birth being the primary objectives or comprised chapter(s); and were the most recently published or updated versions. Data collection and analysis Two reviewers independently assessed guideline quality using the AGREE II instrument, and synthesised consensus and non-consensus recommendations using the content analysis approach. Main results Eleven guidelines met the inclusion criteria. The WHO and NICE guidelines were deemed to have the highest methodological quality. Twenty-three discrepant recommendations and 39 groups of unanimous recommendations (containing 113 individual ones) were identified, among which 14 recommendations including eating and drinking as desired, prophylactic uterotonics, routine amniotomy and episiotomy were included in five or more guidelines. Perineal massage, uterine massage, active or expectant management at the third stage and use of hands-on or hands-poised technique were identified as the main discrepant recommendations. Conclusions Two guidelines with higher methodological quality and key clinical guideline recommendations, including both consensus and non-consensus ones, on uncomplicated birth were identified. Tweetable abstract Clinical guidelines of uncomplicated birth agree and disagree on several key recommendations.

Solar cells capable of light-harvesting during daytime and light-emitting at night are multifunctional semiconductor devices with many potential applications. Here we report that halide perovskite heterojunction interfaces can be refined to yield stable and efficient solar cells. The cell can also operate effectively as an ultralow-voltage light-emitting diode with a peak external quantum efficiency of 3.3%. Spectroscopic and microscopic studies reveal that double-heterojunction refinement with wide-bandgap salts is key to densifying the packing of perovskite grains and enlarging the bandgaps of the perovskite surfaces that are in contact with charge transport semiconductors. The refined perovskite enables a simple device with dual actions of solar cells and light-emitting diodes. This type of all-in-one device has the potential for multifunctional harvesting-storage-utilization systems. This article is protected by copyright. All rights reserved.