Automated Scanning Probe Tip State Classification without Machine Learning.

The manual identification and in situ correction of the state of the scanning probe tip is one of the most time-consuming and tedious processes in atomic-resolution scanning probe microscopy. This is due to the random nature of the probe tip on the atomic level, and the requirement for a human operator to compare the probe quality via manual inspection of the topographical images after any change in the probe. Previous attempts to automate the classification of the scanning probe state have focused on the use of machine learning techniques, but the training of these models relies on large, labeled data sets for each surface being studied. These data sets are extremely time-consuming to create and are not always available, especially when considering a new substrate or adsorbate system. In this paper, we show that the problem of tip classification from a topographical image can be solved by using only a single image of the surface along with a small amount of prior knowledge of the appearance of the system in question with a method utilizing template matching (TM). We find that by using these TM methods, comparable accuracy and precision can be achieved to values obtained with the use of machine learning. We demonstrate the efficacy of this technique by training a machine learning-based classifier and comparing the classifications with the TM classifier for two prototypical silicon-based surfaces. We also apply the TM classifier to a number of other systems where supervised machine learning-based training was not possible due to the nature of the training data sets. Finally, the applicability of the TM method to surfaces used in the literature, which have been classified using machine learning-based methods, is considered.

Precise determination of molecular adsorption geometries by room temperature non-contact atomic force microscopy.

High resolution force measurements of molecules on surfaces, in non-contact atomic force microscopy, are often only performed at cryogenic temperatures, due to needing a highly stable system, and a passivated probe tip (typically via CO-functionalisation). Here we show a reliable protocol for acquiring three-dimensional force map data over both single organic molecules and assembled islands of molecules, at room temperature. Isolated cobalt phthalocyanine and islands of C60 are characterised with submolecular resolution, on a passivated silicon substrate (B:Si(111)-[Formula: see text]). Geometries of cobalt phthalocyanine are determined to a ~ 10 pm accuracy. For the C60, the protocol is sufficiently robust that areas spanning 10 nm × 10 nm are mapped, despite the difficulties of room temperature operation. These results provide a proof-of-concept for gathering high-resolution three-dimensional force maps of networks of complex, non-planar molecules on surfaces, in conditions more analogous to real-world application.

Supporting adolescents' participation in muscle-strengthening physical activity: protocol for the 'Resistance Training for Teens' (RT4T) hybrid type III implementation-effectiveness trial.

INTRODUCTION: In Australia, only 22% of male and 8% of female adolescents meet the muscle-strengthening physical activity guidelines, and few school-based interventions support participation in resistance training (RT). After promising findings from our effectiveness trial, we conducted a state-wide dissemination of the 'Resistance Training for Teens' (RT4T) intervention from 2015 to 2020. Despite high estimated reach, we found considerable variability in programme delivery and teachers reported numerous barriers to implementation. Supporting schools when they first adopt evidence-based programmes may strengthen programme fidelity, sustainability, and by extension, programme impact. However, the most effective implementation support model for RT4T is unclear. OBJECTIVE: To compare the effects of three implementation support models on the reach (primary outcome), dose delivered, fidelity, sustainability, impact and cost of RT4T. METHODS AND ANALYSIS: We will conduct a hybrid type III implementation-effectiveness trial involving grade 9 and 10 (aged 14-16 years) students from 90 secondary schools in New South Wales (NSW), Australia. Schools will be recruited across one cohort in 2023, stratified by school type, socioeconomic status and location, and randomised in a 1:1:1 ratio to receive one of the following levels of implementation support: (1) 'low' (training and resources), (2) 'moderate' (training and resources+external support) or 'high' (training and resources+external support+equipment). Training includes a teacher workshop related to RT4T programme content (theory and practical sessions) and the related resources. Additional support will be provided by trained project officers from five local health districts. Equipment will consist of a pack of semiportable RT equipment (ie, weighted bars, dumbbells, resistance bands and inverted pull up bar stands) valued at ~$A1000 per school. Study outcomes will be assessed at baseline (T0), 6 months (T1) and 18 months (T2). A range of quantitative (teacher logs, observations and teacher surveys) and qualitative (semistructured interviews with teachers) methods will be used to assess primary (reach) and secondary outcomes (dose delivered, fidelity, sustainability, impact and cost of RT4T). Quantitative analyses will use logistic mixed models for dichotomous outcomes, and ordinal or linear mixed effects regression models for continuous outcomes, with alpha levels set at p<0.025 for the outcomes and cost comparisons of the moderate and high support arms against the low support arm. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the University of Newcastle (H-2021-0418), the NSW Department of Education (SERAP:2022215), Hunter New England Human Research Ethics Committee (2023/ETH00052) and the Catholic Schools Office. The design, conduct and reporting will adhere to the Consolidated Standards of Reporting Trials statement, the Standards for Reporting Implementation Studies statement and the Template for Intervention Description and Replication checklist. Findings will be published in open access peer-reviewed journals, key stakeholders will be provided with a detailed report. We will support ongoing dissemination of RT4T in Australian schools via professional learning for teachers. TRIAL REGISTRATION NUMBER: ACTRN12622000861752.

Methods to increase response to postal and electronic questionnaires.

BACKGROUND: Self-administered questionnaires are widely used to collect data in epidemiological research, but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of epidemiological research. OBJECTIVES: To identify effective strategies to increase response to postal and electronic questionnaires. SEARCH METHODS: We searched 14 electronic databases up to December 2021 and manually searched the reference lists of relevant trials and reviews. We contacted the authors of all trials or reviews to ask about unpublished trials; where necessary, we also contacted authors to confirm the methods of allocation used and to clarify results presented. SELECTION CRITERIA: Randomised trials of methods to increase response to postal or electronic questionnaires. We assessed the eligibility of each trial using pre-defined criteria. DATA COLLECTION AND ANALYSIS: We extracted data on the trial participants, the intervention, the number randomised to intervention and comparison groups and allocation concealment. For each strategy, we estimated pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects model. We assessed evidence for selection bias using Egger's weighted regression method and Begg's rank correlation test and funnel plot. We assessed heterogeneity amongst trial odds ratios using a Chi2 test and quantified the degree of inconsistency between trial results using the I2 statistic. MAIN RESULTS: Postal We found 670 eligible trials that evaluated over 100 different strategies of increasing response to postal questionnaires. We found substantial heterogeneity amongst trial results in half of the strategies. The odds of response almost doubled when: using monetary incentives (odds ratio (OR) 1.86; 95% confidence interval (CI) 1.73 to 1.99; heterogeneity I2 = 85%); using a telephone reminder (OR 1.96; 95% CI 1.03 to 3.74); and when clinical outcome questions were placed last (OR 2.05; 95% CI 1.00 to 4.24). The odds of response increased by about half when: using a shorter questionnaire (OR 1.58; 95% CI 1.40 to 1.78); contacting participants before sending questionnaires (OR 1.36; 95% CI 1.23 to 1.51; I2 = 87%); incentives were given with questionnaires (i.e. unconditional) rather than when given only after participants had returned their questionnaire (i.e. conditional on response) (OR 1.53; 95% CI 1.35 to 1.74); using personalised SMS reminders (OR 1.53; 95% CI 0.97 to 2.42); using a special (recorded) delivery service (OR 1.68; 95% CI 1.36 to 2.08; I2 = 87%); using electronic reminders (OR 1.60; 95% CI 1.10 to 2.33); using intensive follow-up (OR 1.69; 95% CI 0.93 to 3.06); using a more interesting/salient questionnaire (OR 1.73; 95% CI 1.12 to 2.66); and when mentioning an obligation to respond (OR 1.61; 95% CI 1.16 to 2.22). The odds of response also increased with: non-monetary incentives (OR 1.16; 95% CI 1.11 to 1.21; I2 = 80%); a larger monetary incentive (OR 1.24; 95% CI 1.15 to 1.33); a larger non-monetary incentive (OR 1.15; 95% CI 1.00 to 1.33); when a pen was included (OR 1.44; 95% CI 1.38 to 1.50); using personalised materials (OR 1.15; 95% CI 1.09 to 1.21; I2 = 57%); using a single-sided rather than a double-sided questionnaire (OR 1.13; 95% CI 1.02 to 1.25); using stamped return envelopes rather than franked return envelopes (OR 1.23; 95% CI 1.13 to 1.33; I2 = 69%), assuring confidentiality (OR 1.33; 95% CI 1.24 to 1.42); using first-class outward mailing (OR 1.11; 95% CI 1.02 to 1.21); and when questionnaires originated from a university (OR 1.32; 95% CI 1.13 to 1.54). The odds of response were reduced when the questionnaire included questions of a sensitive nature (OR 0.94; 95% CI 0.88 to 1.00). Electronic We found 88 eligible trials that evaluated over 30 different ways of increasing response to electronic questionnaires. We found substantial heterogeneity amongst trial results in half of the strategies. The odds of response tripled when: using a brief letter rather than a detailed letter (OR 3.26; 95% CI 1.79 to 5.94); and when a picture was included in an email (OR 3.05; 95% CI 1.84 to 5.06; I2 = 19%). The odds of response almost doubled when: using monetary incentives (OR 1.88; 95% CI 1.31 to 2.71; I2 = 79%); and using a more interesting topic (OR 1.85; 95% CI 1.52 to 2.26). The odds of response increased by half when: using non-monetary incentives (OR 1.60; 95% CI 1.25 to 2.05); using shorter e-questionnaires (OR 1.51; 95% CI 1.06 to 2.16; I2 = 94%); and using a more interesting e-questionnaire (OR 1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third when: offering survey results as an incentive (OR 1.36; 95% CI 1.16 to 1.59); using a white background (OR 1.31; 95% CI 1.10 to 1.56); and when stressing the benefits to society of response (OR 1.38; 95% CI 1.07 to 1.78; I2 = 41%). The odds of response also increased with: personalised e-questionnaires (OR 1.24; 95% CI 1.17 to 1.32; I2 = 41%); using a simple header (OR 1.23; 95% CI 1.03 to 1.48); giving a deadline (OR 1.18; 95% CI 1.03 to 1.34); and by giving a longer time estimate for completion (OR 1.25; 95% CI 0.96 to 1.64). The odds of response were reduced when: "Survey" was mentioned in the e-mail subject (OR 0.81; 95% CI 0.67 to 0.97); when the email or the e-questionnaire was from a male investigator, or it included a male signature (OR 0.55; 95% CI 0.38 to 0.80); and by using university sponsorship (OR 0.84; 95%CI 0.69 to 1.01). The odds of response using a postal questionnaire were over twice those using an e-questionnaire (OR 2.33; 95% CI 2.25 to 2.42; I2 = 98%). Response also increased when: providing a choice of response mode (electronic or postal) rather than electronic only (OR 1.76 95% CI 1.67 to 1.85; I2 = 97%); and when administering the e-questionnaire by computer rather than by smartphone (OR 1.62 95% CI 1.36 to 1.94). AUTHORS' CONCLUSIONS: Researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this Cochrane review.

Clinical Observation, Management and Function Of low back pain Relief Therapies (COMFORT): A cluster randomised controlled trial protocol.

INTRODUCTION: Low back pain (LBP) is commonly treated with opioid analgesics despite evidence that these medicines provide minimal or no benefit for LBP and have an established profile of harms. International guidelines discourage or urge caution with the use of opioids for back pain; however, doctors and patients lack practical strategies to help them implement the guidelines. This trial will evaluate a multifaceted intervention to support general practitioners (GPs) and their patients with LBP implement the recommendations in the latest opioid prescribing guidelines. METHODS AND ANALYSIS: This is a cluster randomised controlled trial that will evaluate the effect of educational outreach visits to GPs promoting opioid stewardship alongside non-pharmacological interventions including heat wrap and patient education about the possible harms and benefits of opioids, on GP prescribing of opioids medicines dispensed. At least 40 general practices will be randomised in a 1:1 ratio to either the intervention or control (no outreach visits; GP provides usual care). A total of 410 patient-participants (205 in each arm) who have been prescribed an opioid for LBP will be enrolled via participating general practices. Follow-up of patient-participants will occur over a 1-year period. The primary outcome will be the cumulative dose of opioid dispensed that was prescribed by study GPs over 1 year from the enrolment visit (in morphine milligram equivalent dose). Secondary outcomes include prescription of opioid medicines, benzodiazepines, gabapentinoids, non-steroidal anti-inflammatory drugs by study GPs or any GP, health services utilisation and patient-reported outcomes such as pain, quality of life and adverse events. Analysis will be by intention to treat, with a health economics analysis also planned. ETHICS AND DISSEMINATION: The trial received ethics approval from The University of Sydney Human Research Ethics Committee (2022/511). The results will be disseminated via publications in journals, media and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12622001505796.

Laboratory Comparison of Low-Cost Particulate Matter Sensors to Measure Transient Events of Pollution-Part B-Particle Number Concentrations.

Low-cost Particulate Matter (PM) sensors offer an excellent opportunity to improve our knowledge about this type of pollution. Their size and cost, which support multi-node network deployment, along with their temporal resolution, enable them to report fine spatio-temporal resolution for a given area. These sensors have known issues across performance metrics. Generally, the literature focuses on the PM mass concentration reported by these sensors, but some models of sensors also report Particle Number Concentrations (PNCs) segregated into different PM size ranges. In this study, eight units each of Alphasense OPC-R1, Plantower PMS5003 and Sensirion SPS30 have been exposed, under controlled conditions, to short-lived peaks of PM generated using two different combustion sources of PM, exposing the sensors' to different particle size distributions to quantify and better understand the low-cost sensors performance across a range of relevant environmental ranges. The PNCs reported by the sensors were analysed to characterise sensor-reported particle size distribution, to determine whether sensor-reported PNCs can follow the transient variations of PM observed by the reference instruments and to determine the relative impact of different variables on the performances of the sensors. This study shows that the Alphasense OPC-R1 reported at least five size ranges independently from each other, that the Sensirion SPS30 reported two size ranges independently from each other and that all the size ranges reported by the Plantower PMS5003 were not independent of each other. It demonstrates that all sensors tested here could track the fine temporal variation of PNCs, that the Alphasense OPC-R1 could closely follow the variations of size distribution between the two sources of PM, and it shows that particle size distribution and composition are more impactful on sensor measurements than relative humidity.

Oligofructose alone and in combination with 2'fucosyllactose induces physiologically relevant changes in γ-aminobutyric acid and organic acid production compared to sole 2'fucosyllactose supplementation: an in vitro study.

We explored the potential for the prebiotic oligofructose and prebiotic candidate 2'fucosyllactose, alone and in combination (50:50 blend) to induce physiologically relevant increases in neurotransmitter (γ-aminobutyric acid, serotonin, tryptophan, and dopamine) and organic acid (acetate, propionate, butyrate, lactate, and succinate) production as well as microbiome changes using anaerobic pH-controlled in vitro batch culture fermentations over 48 h. Changes in organic acid and neurotransmitter production were assessed by gas chromatography and liquid chromatography and, bacterial enumeration using fluorescence in situ hybridization, respectively. Both oligofructose and oligofructose/2'fucosyllactose combination fermentations induced physiologically relevant concentrations of γ-aminobutyric acid, acetate, propionate, butyrate, and succinate at completion (all P ≤ .05). A high degree of heterogeneity was seen amongst donors in both neurotransmitter and organic acid production in sole 2'FL fermentations suggesting a large responder/nonresponder status exists. Large increases in Bifidobacterium, Lactobacillus, and Bacteroides numbers were detected in oligofructose fermentation, smallest increases being detected in 2'fucosyllactose fermentation. Bacterial numbers in the combined oligofructose/2'fucosyllactose fermentation were closer to that of sole oligofructose. Our results indicate that oligofructose and oligofructose/2'fucosyllactose in combination have the potential to induce physiologically relevant increases in γ-aminobutyric and organic acid production along with offsetting the heterogenicity seen in response to sole 2'fucosyllactose supplementation.

Rhythm vs. Rate Control in Patients with Postoperative Atrial Fibrillation after Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review to compare the effects of rhythm vs. rate control in this population. METHODS: We searched MEDLINE, Embase and CENTRAL to March 2023. We included randomized trials and observational studies comparing rhythm to rate control in cardiac surgery patients with POAF. We used a random-effects model to meta-analyze data and rated the quality of evidence using GRADE. RESULTS: From 8,110 citations, we identified 8 randomized trials (990 patients). Drug regimens used for rhythm control included amiodarone in four trials, other class III anti-arrhythmics in one trial, class I anti-arrhythmics in four trials and either a class I or III anti-arrhythmic in one trial. Rhythm control compared to rate control did not result in a significant difference in length of stay (mean difference -0.8 days; 95% CI -3.0 to +1.4, I2 = 97%), AF recurrence within 1 week (130 events; risk ratio [RR] 1.1; 95%CI 0.6-1.9, I2 = 54%), AF recurrence up to 1 month (37 events; RR 0.9; 95%CI 0.5-1.8, I2 = 0%), AF recurrence up to 3 months (10 events; RR 1.0; 95%CI 0.3-3.4, I2 = 0%) or mortality (25 events; RR 1.6; 95%CI 0.7-3.5, I2 = 0%). Effect measures from seven observational studies (1428 patients) did not differ appreciably from those in randomized trials. CONCLUSIONS: Although atrial fibrillation is common after cardiac surgery, limited low-quality data guide its management. Limited available evidence suggests no clear advantage to either rhythm or rate control. A large-scale randomized trial is needed to inform this important clinical question.

Oligofructose, 2'fucosyllactose and ß-glucan in combination induce specific changes in microbial composition and short-chain fatty acid production compared to sole supplementation.

AIMS: In this study, we explored the effects that the prebiotic inulin-type fructans, and prebiotic candidates: 2'fucosyllactose and ß-glucan from barley, singular and in combination had on microbial load, microbiome profile, and short-chain fatty acid production. This was carried out as a prescreening tool to determine combinations that could be taken forward for use in a human intervention trial. METHODS AND RESULTS: Effects of inulin-type fructans, 2'fucosyllactose and ß-glucan from barley in singular and combination on microbial load and profile and short-chain fatty acid production (SCFA) was conducted using in vitro batch culture fermentation over 48 h. Changes in microbial load and profile were assessed by fluorescence in situ hybridization flow cytometry (FISH-FLOW) and 16S rRNA sequencing, and changes in SCFA via gas chromatography. All substrates generated changes in microbial load and profile, achieving peak microbial load at 8 h fermentation with the largest changes in profile across all substrates in Bifidobacterium (Q < 0.05). This coincided with significant increases in acetate observed throughout fermentation (Q < 0.05). In comparison to sole supplementation combinations of oligofructose, ß-glucan and 2'fuscosyllactose induced significant increases in both propionate and butyrate producing bacteria (Roseburia and Faecalibacterium praunitzii), and concentrations of propionate and butyrate, the latter being maintained until the end of fermentation (all Q < 0.05). CONCLUSIONS: Combinations of oligofructose, with ß-glucan and 2'fucosyllactose induced selective changes in microbial combination and SCFA namely Roseburia, F. praunitzii, propionate and butyrate compared to sole supplementation.

Intramolecular Force Mapping at Room Temperature.

Acquisition of dense, three-dimensional, force fields with intramolecular resolution via noncontact atomic force microscopy (NC-AFM) has yielded enormous progress in our ability to characterize molecular and two-dimensional materials at the atomic scale. To date, intramolecular force mapping has been performed exclusively at cryogenic temperatures, due to the stability afforded by low temperature operation, and as the carbon monoxide functionalization of the metallic scanning probe tip, normally required for submolecular resolution, is only stable at low temperature. In this paper we show that high-resolution, three-dimensional force mapping of a single organic molecule is possible even at room temperature. The physical limitations of room temperature operation are overcome using semiconducting materials to inhibit molecular diffusion and create robust tip apexes, while challenges due to thermal drift are overcome with atom tracking based feedforward correction. Three-dimensional force maps comparable in spatial and force resolution to those acquired at low temperature are demonstrated, permitting a quantitative analysis of the adsorption induced changes in the geometry of the molecule at the picometer level.

Inulin-type fructans and short-chain fructooligosaccharides-their role within the food industry as fat and sugar replacers and texture modifiers-what needs to be considered!

Inulin and oligofructose are classes of prebiotics belonging to a group of nondigestible carbohydrates referred to as inulin-type fructans. While short-chain fructooligosaccharides are enzymatically synthesized from the hydrolysis and transglycosylation of sucrose. Inulin-type fructans and short-chain fructooligosaccharides act as carbon sources for selective pathways supporting digestive health including altering the composition of the gut microbiota along with improving transit time. Due to their physicochemical properties, inulin-type fructans and short-chain fructooligosaccharides have been widely used in the food industry as partial replacements for both fat and sugar. Yet, levels of replacement need to be carefully considered as it may result in changes to physical and sensory properties that could be detected by consumers. Furthermore, it has been reported depending on the processing parameters used during production that inulin-type fructans and short-chain fructooligosaccharides may or may not undergo structural alterations. Therefore, this paper reviews the role of inulin-type fructans and short-chain fructooligosaccharides within the food industry as fat and sugar replacers and texture modifiers, their impact on final sensory properties, and to what degree processing parameters are likely to impact their functional properties.

Associations of long chain polyunsaturated fatty acids with bone mineral density and bone turnover in postmenopausal women.

PURPOSE: The immunomodulatory properties of n-3 long chain polyunsaturated fatty acids (LCPUFA) are reported to reduce bone loss through alteration of bone remodelling and n-3 LCPUFA, therefore, may benefit bone health in post-menopausal women, a vulnerable group at high risk of osteoporosis. METHODS: Measures of bone mineral density (BMD) were determined using dual energy X-ray absorptiometry (DEXA) in 300 post-menopausal women. The bone turnover markers osteocalcin (OC), C-terminal telopeptides of type 1 collagen (CTX) and total alkaline phosphatase were quantified in serum along with urinary creatinine corrected deoxypyridinoline (DPD/Cr) and CTX/Cr and the CTX:OC ratio calculated. Total serum n-6 PUFA (LA + AA) and n - 3 LCPUFA (ALA + EPA + DPA + DHA) were measured and the n - 6:n - 3 ratio was calculated. RESULTS: Mean (SD) age and body mass index (BMI) were 61 (6.4) years and 27.4 (4.8) kg/m2, respectively with participants being 12.6 (7.6) years post-menopause. Multiple regression analysis identified no association between n-3 LCPUFA and any of the measures of T-score or BMD albeit a significant positive association between total n - 3 LCPUFA and femur BMD (ß = 0.287; p = 0.043) was observed within those women with a low n - 6:n - 3 ratio. There was a significant inverse association between ALA and urinary DPD/Cr (ß = - 0.141; p = 0.016). CONCLUSION: A favourable low n - 6:n - 3 ratio was associated with higher femur BMD and a higher n - 3 LCPUFA (ALA) was associated with lower bone resorption. These results support a beneficial role for n - 3 LCPUFA in reducing postmenopausal bone resorption and favourably influencing BMD. TRIAL NUMBER & DATE OF REGISTRATION: ISRCTN63118444, 2nd October 2009, "Retrospectively registered".

Final Results of TACTICS: A Randomized, Prospective Trial Comparing Transarterial Chemoembolization Plus Sorafenib to Transarterial Chemoembolization Alone in Patients with Unresectable Hepatocellular Carcinoma.

Introduction: Several clinical trials comparing the efficacy and safety of transarterial chemoembolization (TACE) plus molecular-targeted agents versus TACE alone revealed no clinical benefits in progression-free survival (PFS) or overall survival (OS). Here, we report the final OS analysis from the TACTICS trial, which previously demonstrated significant improvement in PFS with TACE plus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) (NCT01217034). Methods: Patients with unresectable HCC were randomized to a TACE plus sorafenib group (N = 80) or a TACE alone group (N = 76). Patients in the combination treatment group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable progression. In this trial, TACE-specific PFS was used. TACE-specific PFS is defined as the time from randomization to progressive disease (PD) or death from any cause, and PD was defined as untreatable progression, caused by the inability of a patient to further receive or benefit from TACE for reasons that include intrahepatic tumor progression (25% increase vs. baseline) according to response evaluation criteria in cancer of the liver, the detection of extrahepatic spread, vascular invasion, or transient deterioration of liver function to Child-Pugh C after TACE. Results: At the cut-off date of July 31, 2020, 131 OS events were observed. The median OS was 36.2 months with TACE plus sorafenib and 30.8 months with TACE alone (hazard ratio [HR] = 0.861; 95% confidence interval [CI], 0.607-1.223; p = 0.40, ΔOS, 5.4 months). The updated PFS was 22.8 months with TACE plus sorafenib and 13.5 months with TACE alone (HR = 0.661; 95% CI, 0.466-0.938; p = 0.02). Post-trial treatments with active procedures/agents were received by 47 (58.8%) patients in the TACE plus sorafenib group and 58 (76.3%) in the TACE alone group (p = 0.01). In post hoc analysis, PFS and OS benefit were shown in HCC patients with tumor burden beyond up-to-7 criteria. Conclusions: In TACTICS trial, TACE plus sorafenib did not show significant OS benefit over TACE alone; however, clinical meaningful OS prolongation and significantly improved PFS was observed. Thus, the TACE plus sorafenib can be considered a choice of treatment in intermediate-stage HCC, especially in patients with high tumor burden. Trial Registration: NCT01217034.

Salicylic acid fights against Fusarium wilt by inhibiting target of rapamycin signaling pathway in Fusarium oxysporum.

INTRODUCTION: Biofungicides with low toxicity and high efficiency are a global priority for sustainable agricultural development. Phytohormone salicylic acid (SA) is an ancient medicine against various diseases in humans and activates the immune system in plants, but little is known of its function as a biofungicide. OBJECTIVES: Here, Fusarium oxysporum, the causal agent of devastating Fusarium wilt and immunodepressed patients, was used as a model system to explore whether SA can enter the pathogen cells and suppress key targets of the pathogen. METHODS: Oxford Nanopore MinION sequencing and high-throughput chromosome conformation capture (Hi-C) sequencing were used to analyzed the genome of F. oxysporum. In addition, RNA-seq, qRT-PCR, and western blotting were conducted to detect gene and protein expression levels. RESULTS: We isolated and sequenced the genome of F. oxysporum from potato dry rot, and the F. oxysporum included 12 chromosomes and 52.3 Mb genomic length. Pharmacological assays showed that exogenous application of SA can efficiently arrest hyphal growth, spore production, and pathogenicity of F. oxysporum, whereas endogenous salicylate hydroxylases significantly detoxify SA. The synergistic growth inhibition of F. oxysporum was observed when SA was combined with rapamycin. Kinase assays showed that SA inhibits FoTOR complex 1 (FoTORC1) by activating FoSNF1 in vivo. Transgenic potato plants with the interference of FoTOR1 and FoSAH1 genes inhibited the invasive growth of hyphae and significantly prevented the occurrence of Fusarium wilt. CONCLUSION: This study revealed the underlying mechanisms of SA against F. oxysporum and provided insights into SA in controlling various fungal diseases by targeting the SNF1-TORC1 pathway of pathogens.

A human adipose tissue cell-type transcriptome atlas.

The importance of defining cell-type-specific genes is well acknowledged. Technological advances facilitate high-resolution sequencing of single cells, but practical challenges remain. Adipose tissue is composed primarily of adipocytes, large buoyant cells requiring extensive, artefact-generating processing for separation and analysis. Thus, adipocyte data are frequently absent from single-cell RNA sequencing (scRNA-seq) datasets, despite being the primary functional cell type. Here, we decipher cell-type-enriched transcriptomes from unfractionated human adipose tissue RNA-seq data. We profile all major constituent cell types, using 527 visceral adipose tissue (VAT) or 646 subcutaneous adipose tissue (SAT) samples, identifying over 2,300 cell-type-enriched transcripts. Sex-subset analysis uncovers a panel of male-only cell-type-enriched genes. By resolving expression profiles of genes differentially expressed between SAT and VAT, we identify mesothelial cells as the primary driver of this variation. This study provides an accessible method to profile cell-type-enriched transcriptomes using bulk RNA-seq, generating a roadmap for adipose tissue biology.

Thermodynamic Driving Forces for Substrate Atom Extraction by Adsorption of Strong Electron Acceptor Molecules.

A quantitative structural investigation is reported, aimed at resolving the issue of whether substrate adatoms are incorporated into the monolayers formed by strong molecular electron acceptors deposited onto metallic electrodes. A combination of normal-incidence X-ray standing waves, low-energy electron diffraction, scanning tunnelling microscopy, and X-ray photoelectron spectroscopy measurements demonstrate that the systems TCNQ and F4TCNQ on Ag(100) lie at the boundary between these two possibilities and thus represent ideal model systems with which to study this effect. A room-temperature commensurate phase of adsorbed TCNQ is found not to involve Ag adatoms, but to adopt an inverted bowl configuration, long predicted but not previously identified experimentally. By contrast, a similar phase of adsorbed F4TCNQ does lead to Ag adatom incorporation in the overlayer, the cyano end groups of the molecule being twisted relative to the planar quinoid ring. Density functional theory (DFT) calculations show that this behavior is consistent with the adsorption energetics. Annealing of the commensurate TCNQ overlayer phase leads to an incommensurate phase that does appear to incorporate Ag adatoms. Our results indicate that the inclusion (or exclusion) of metal atoms into the organic monolayers is the result of both thermodynamic and kinetic factors.

Heart failure decompensation alerts in a patient's home using an automated, AI-driven, point-of-care device.

Heart failure (HF) is a major challenge worldwide and needs continuous monitoring of patients even after hospital discharge. This case report summarises the data collected and experience gained from the first usage of an automated, point-of-care device (Heartfelt device) in a patient's home in the UK. The device monitors the onset of peripheral oedema and alerts clinicians if an increase in volume outside an expected normal range for the patient is detected. This may provide a reliable method of remotely and automatically monitoring HF patients in the home for those who do not reliably use weighing scales. The device successfully provided data for about 15 months and generated alerts in advance, which supported decisions for the patient's care. The rate of data acquisition was very high and consistent throughout this period. The patient was satisfied with the device and agreed that it helped in her decision to seek medical attention.

Identification of mRNA 5' cap-associated proteins in the human malaria parasite Plasmodium falciparum.

Eukaryotic messenger RNA is translated via a 5' cap-dependent initiation mechanism. Experimental evidence for proteins involved with translation initiation among eukaryotic parasites is lacking, including Plasmodium falciparum, the human malaria parasite. Native P. falciparum proteins from asexual stage parasites were enriched using a 5' cap affinity matrix. Proteomic analysis of enriched protein eluates revealed proteins putatively associated with the 5' cap. The canonical 5' cap-binding protein eIF4E (PF3D7_0315100) was the most reproducibly enriched protein. The eIF4A and eIF4G proteins hypothesized to form the eIF4F initiation complex with eIF4E were also detected as 5' cap enriched, albeit with low reproducibility. Surprisingly, enolase (ENO) was the second most enriched protein after eIF4E. Recombinant ENO protein did not demonstrate 5' cap activity, suggesting an indirect association of the native ENO with the 5' cap.