Objectives: To assess the efficacy and tolerance of the conventional first-line treatment by methotrexate (MTX) and corticosteroids (CS) in patients with juvenile dermatomyositis (JDM) regardless of severity.

Methods: We conducted a monocentric retrospective study of patients with newly-diagnosed JDM treated with MTX and CS from 2012 to 2020. Proportion of clinically inactive disease (CID) within six months of MTX initiation was evaluated using both PRINTO criteria (evaluating muscle inactive disease) and Disease Activity Score (evaluating skin inactive disease). We compared responders and non-responders using univariate analyses.

Results: Forty-five patients with JDM, out of which thirty (67%) severe JDM, were included. After six months of treatment with MTX and CS, complete CID, muscle CID and skin CID were achieved in 14/45 (31%), 19/45 (42%) and 15/45 (33%) patients respectively. The absence of myositis-specific (MSA) or myositis-associated autoantibodies (MAA) at diagnosis was associated with a better overall, cutaneous and muscular therapeutic response, compared with antibody-positive forms (p< 0.01). Requirement for ICU (p= 0.029) and cutaneous ulcerations (p= 0.018) were associated to a less favorable muscle response. MTX was stopped due to intolerance in six patients (13%) before month 6.

Conclusion: Conventional first-line treatment with MTX was not efficient in a large subset of JDM patients, especially in patients with MSA-positive forms, and in patients with severe JDM. Larger multicentre cohorts are required to confirm these data and to identify new predictive biomarkers of MTX response, in order to treat patients with JDM as early as possible with appropriate targeted drugs.

Keywords: juvenile dermatomyositis; methotrexate; paediatric rheumatology.

Background: Little is known about the epidemiology and patterns of care of intrahepatic cholangiocarcinoma (iCCA) in daily clinical practice. The aims of this study were to estimate the number of declared cases during the study period 2014-2015 in France from a hospitalization database and to describe the healthcare trajectories of these patients.

Methods: A retrospective analysis was carried out using the French nationwide prospective hospitalization database. All pts with a new diagnosis of "carcinoma of the intrahepatic bile duct" who had a first hospital stay in the Medicine, Surgery and Obstetrics departments (MSO) between 2014 and 2015 with a 2-year follow-up were included. Data related to the first identified stay (S1) in the MSO and on all subsequent stays in the MSO, aftercare and rehabilitation or home hospitalization were analysed.

Findings: A total of 3650 new iCCA cases were identified. At S1 (admission via emergency room (ER) in 28%), the median age of the patients was 73 years, 57% were male and 35% had metastases. Jaundice/anaemia/ascites/cholangitis were reported in 17%/16%/12%/7% of patients, respectively. The care of patients at S1 was mainly provided in general hospitals (CHG, 60%). A total of 896 (24%) patients died during S1. They were more frequently hospitalized via the ER (48% vs 23%), metastatic (52% vs 35%) and symptomatic. Subsequent stays were identified for 2507 (69%) patients. Three healthcare pathways were defined: surgery (n = 519; 14%), chemotherapy (CT) without surgery (n = 812; 22%) and best supportive care (BSC) (n = 2319; 63%). CT, surgery and BSC were most frequently performed in the cancer centres, university hospitals and CHG, respectively.

Interpretation: This medico administrative study reveals a higher number of iCCA cases than that previously reported by registries and highlights the severity of this disease.

Funding: This study was sponsored by Incyte Biosciences International Sàrl., Geneva, Switzerland. INCYTE validated the design of the study, the analysis, the interpretation of data and the writing of the manuscript which was first written by the 2 experts and CEMKA.

Keywords: Epidemiology; French PMSI database; Intrahepatic cholangiocarcinoma; Patterns of care; Real life.

Cardiotoxicity is a serious adverse effect of an anticancer drug, doxorubicin (DOX), which can occur within a year or decades after completion of therapy. The present study was designed to address a knowledge gap concerning a lack of circulating biomarkers capable of predicting the risk of cardiotoxicity induced by DOX. Profiling of 2083 microRNAs (miRNAs) in mouse plasma revealed 81 differentially expressed miRNAs one week after 6, 9, 12, 18, or 24 mg/kg total cumulative DOX doses (early-onset model) or saline (SAL). Among these, the expression of 7 miRNAs were altered prior to the onset of myocardial injury at 12 mg/kg and higher cumulative doses. The expression of only miR-34a-5p was significantly (FDR<0.1) elevated at all total cumulative doses compared to concurrent SAL-treated controls and showed a statistically significant dose-related response. The trend in plasma miR-34a-5p expression levels during DOX exposures also correlated with a significant dose-related increase in cardiac expression of miR-34a-5p in these mice. Administration of a cardioprotective drug, dexrazoxane, to mice before DOX treatment, significantly mitigated miR-34a-5p expression in both plasma and heart in conjunction with attenuation of cardiac pathology. This association between plasma and heart may suggest miR-34a-5p as a potential early circulating marker of early-onset DOX cardiotoxicity. In addition, higher expression of miR-34a-5p (FDR<0.1) in plasma and heart compared to SAL-treated controls 24 weeks after 24 mg/kg total cumulative DOX dose, when cardiac function was altered in our recently established delayed-onset cardiotoxicity model, indicated its potential as an early biomarker of delayed-onset cardiotoxicity.

Keywords: Doxorubicin; delayed-onset cardiotoxicity; dexrazoxane; early-onset cardiotoxicity; microRNA sequencing; microRNA-34a-5p; mouse plasma.

Background: Thromboembolic events frequently complicate the course of malignancy and represent a major cause of morbidity and mortality in cancer patients. In contrast to chemotherapy and other systemic therapies, little is known about the impact of ionizing radiations on the incidence of venous thromboembolism (VTE) in cancer patients.

Methods: In the present prospective study, we aimed to investigate the incidence, management, and outcome of VTE in newly diagnosed cancer patients who received curative radiotherapy.

Results: VTE was found in 8 patients, out of 401 patients at a median time of 80 days after radiotherapy initiation. The incidence rate of VTE at 6 months post-treatment was 2% (95% CI, 0.9-3.7), with 50% of cases occurring during the radiotherapy course and 50% of cases in patients who received or were receiving chemotherapy. As none of the patients harbored a personal history of VTE, no prophylactic measure was initiated during cancer therapy. Most patients received monotherapy with low-molecular-weight heparin and were still on surveillance at the end of the study. No specific clinical risk factor was identified that might systematically indicate the need of thromboprophylaxis in the context of curative radiotherapy.

Conclusions: Although this pan-cancer descriptive study did not relate an increased risk of short-term thrombosis following ionizing radiation, it provides important insight as a basis for future studies with subcategories of cancer, in order to in fine guide further recommendations in frail patients.

Clinical trial registration number: NCT02696447.

Keywords: ionizing radiation; pan-cancer; prophylaxis; radiotherapy; venous thromboembolism.

Purpose: Segmenting the organs from computed tomography (CT) images is crucial to early diagnosis and treatment. Pancreas segmentation is especially challenging because the pancreas has a small volume and a large variation in shape.

Methods: To mitigate this issue, an attention-guided duplex adversarial U-Net (ADAU-Net) for pancreas segmentation is proposed in this work. First, two adversarial networks are integrated into the baseline U-Net to ensure the obtained prediction maps resemble the ground truths. Then, attention blocks are applied to preserve much contextual information for segmentation. The implementation of the proposed ADAU-Net consists of two steps: 1) backbone segmentor selection scheme is introduced to select an optimal backbone segmentor from three two-dimensional segmentation model variants based on a conventional U-Net and 2) attention blocks are integrated into the backbone segmentor at several locations to enhance the interdependency among pixels for a better segmentation performance, and the optimal structure is selected as a final version.

Results: The experimental results on the National Institutes of Health Pancreas-CT dataset show that our proposed ADAU-Net outperforms the baseline segmentation network by 6.39% in dice similarity coefficient and obtains a competitive performance compared with the-state-of-art methods for pancreas segmentation.

Conclusion: The ADAU-Net achieves satisfactory segmentation results on the public pancreas dataset, indicating that the proposed model can segment pancreas outlines from CT images accurately.

Keywords: attention block; backbone segmentor; generative adversarial network; pancreatic segmentation.

Regulating Lewis acid-base sites in catalysts to investigate their influence in the chemical fixation of CO2 is significant but challenging. A metal-organic framework (MOF) with open metal Co sites, {(NH2Me2)[Co3(μ3-OH)(BTB)2(H2O)]· 9H2O·5DMF}n (1), was obtained and the results of catalytic investigation show that 1 can catalyze cycloaddition of CO2 and aziridines with 99% yield. The efficiency in the cyclization of CO2 with propargyl amines is only 32%. To improve the catalytic ability of 1, ligand XN with Lewis base sites was introduced into 1 and coordinated with the open Co sites, resulting in a decrease of the Lewis acid sites and an increase in the Lewis base sites in a related MOF 2 ({(NH2Me2)[Co3-(μ3-OH)(NHMe2)(BTB)2(XN)]·8H2O·4DMF}n). Selective regulation of the type of active centers causes the yield of oxazolidinones to be enhanced about 2.4 times, suggesting that this strategy can turn on/off the catalytic activity for different reactions. The catalytic results from 2 treated with acid solution support this conclusion. This work illuminates a MOF-construction strategy that produces efficient catalysts for CO2 conversion.

Keywords: CO2 Conversion; Catalytic selectivity; Lewis acid/base sites; MOFs catalyst; Oxazolidinones.

A substantially improved method for living polymerization of N -propargylamides and their derivatives has been developed. Rhodium(I) complexes bearing an aryl-substituted 1,3,5-hexatriene chain can work as excellent initiators of the polymerization of such non-conjugated terminal alkynes to give the corresponding cis -stereoregular polymers having a narrow molecular weight distribution. The typical living nature has been confirmed by investigating the effects of initial feed ratios of the monomer to the initiator on the molecular weight of the resulting polymers as well as multistage polymerization. Moreover, we demonstrated that the present method enables functionalization of both polymer chain ends and synthesis of novel block co-polymers consisting of poly( N -propargylamide) and poly(phenylacetylene) blocks with a narrow molecular weight distribution.

Keywords: Alkynes; Insertion; Polymers; polymerization; rhodium.

Purpose: Cholestasis due to benign biliary strictures is the most common biliary complication after pediatric split liver transplantation (SLT), decreasing graft survival, but consensus about its management lacks. Percutaneous transhepatic cholangiography, bilioplasty and internal-external biliary drainage (IEBD) are standard treatments. The aim of this report is to present the preliminary experience with a new biodegradable biliary stent in the management of post-SLT biliary strictures.

Materials and methods: Between September 2020 and April 2021, SLT patients with a single anastomotic benign biliary stricture underwent percutaneous transhepatic implantation of an innovative 10F helical-shaped biodegradable biliary stent, featuring a slow degradation profile, in addition to the standard treatment with bilioplasty and IEBD. The device is unique and the first to be CE-marked for the use in this indication.

Results: Six pediatric patients (4 males; median age 8.6 years, interquartile range 3.7 years) underwent percutaneous stent implantation, without complications nor clinical cholestasis during a median follow-up of 271 days (IQR 120.25). Stent dislodgement occurred in one case.

Conclusion: Preliminary data suggest that implantation of a new biodegradable biliary stent may be considered in the management of post-SLT cholestasis in pediatric patients. Some technical tips are useful during implantation. This device may prolong biliary drainage, potentially relieving the discomfort of long-term IEBD.

Keywords: Cholestasis; Drainage; Liver transplantation; Stents.

Keywords: Lateral medullary infarction; Peripheral facial palsy; Thin-section diffusion-weighted images.

Purpose: To analyze and characterize the online plan adaptation of 1.5T magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) of prostate cancer (PC).

Methods: PC patients (n = 107) who received adaptive 1.5 Tesla MRgSBRT were included. Online plan adaptation was implemented by either the adapt-to-position (ATP) or adapt-to-shape (ATS) methods. Patients were assigned to the ATS group if they underwent ≥ 1 ATS fraction (n = 51); the remainder were assigned to the ATP group (n = 56). The online plan adaptation records of 535 (107 × 5) fractions were retrospectively reviewed. Rationales for ATS decision-making were determined and analyzed using predefined criteria. Statistics of ATS fractions were summarized. Associations of patient characteristics and clinical factors with ATS utilization were investigated.

Results: There were 87 (16.3%) ATS fractions and 448 ATP fractions (83.7%). The numbers of ATS adoptions in fractions 1-5 were 29 (29/107, 27.1%), 18 (16.8%), 15 (14.0%), 16 (15.0%), and 9 (8.4%), respectively, with significant differences in adoption frequency between fractions (p = 0.007). Other baseline patient characteristics and clinical factors were not significantly associated with ATS classification (all p > 0.05). Underlying criteria for the determination of ATS implementation comprised anatomical changes (77 fractions in 50 patients) and discrete multiple targets (15 fractions in 3 patients). No ATS utilization was determined using dosimetric or online quality assurance criteria.

Conclusions: This study contributes to facilitating the establishment of a standardized protocol for online MR-guided adaptive radiotherapy in PC.

Keywords: Adapt-to-position (ATP); Adapt-to-shape (ATS); Magnetic resonance guided radiotherapy (MRgRT); Online plan adaptation; Prostate cancer (PC); Stereotactic body radiotherapy (SBRT).

The authors have observed a vertebral anomaly in French and English Bulldogs and termed this anomaly "vertebral vascular canal dysplasia (VVCD)." No previously published descriptions of this anomaly were found. The aims of this retrospective, multi-institutional, observational study were to (1) describe the clinical, CT, and MRI characteristics of VVCD, and (2) estimate the prevalence and describe the characteristics of VVCD in a group of French and English Bulldogs. For descriptions of the anomaly, medical records and imaging studies of nine clinical cases with VVCD from several countries were reviewed. For estimation of prevalence, imaging studies of French and English Bulldogs from the United Kingdom (UK) and Italy were reviewed. All clinical case dogs had ≥5 thoracic vertebrae with VVCD affecting >50% of vertebral body height (VBH). The prevalence of VVCD involving ≥1 thoracic vertebra in the UK population (CT identified) of English Bulldogs and French Bulldogs was, respectively, 83.3% (30/36) and 68.3% (28/41). English Bulldogs had significantly more thoracic vertebrae with VVCD than French Bulldogs (P = < 0.01). The prevalence of VVCD in ≥1 thoracic vertebra in the Italian population (MRI identified) of English Bulldogs and French Bulldogs was, respectively, 21.7% (5/23) and 6.6% (7/106). Vertebral vascular canal dysplasia was observed in normal as well as in malformed vertebrae (e.g., hemivertebrae). Findings from the current study introduced descriptions of VVCD that can be used as background for future studies.

Keywords: basivertebral canal; congenital; vertebral anomaly; vertebral malformation.

Keywords: COVID-19; SARS-CoV-2; biomarker; exercise; heart.

Context-specific control mechanisms of hypoxia-inducible transcription factors HIF-1alpha and HIF-2alpha in tumors exposed to oxygen shortage remain incompletely understood. In this issue, Zhang et al (2022) identify a deubiquitinase that differentially stabilizes HIF-2alpha in stem-like glioblastoma cells, suggesting potential implications for regulation of the hypoxic response in a wide array of tissues and cancers.

An oxidative-decarboxylative intramolecular cyclisation of dipeptide derivatives is reported. This transformation is promoted by phenyl iodine(III) diacetate (PIDA) in combination with BF₃·OEt₂. The reaction gives access to a variety of valuable polycyclic N-heterocyclic scaffolds containing 5-, 6-, or 7-membered rings.

Environmental enrichment (EE) in rodents is associated with a wide range of physiological, affective, and cognitive benefits. A seemingly opposite housing condition, social isolation (SI), is used as a rodent model of stress, negatively affecting several neurobiological mechanisms and hampering cognitive performance. Experimental designs that involve switching between these housing conditions produced mixed results. We evaluated different behavioral and cognitive effects of brief EE following long-term, SI-induced stress. We revealed the influence of enrichment after 30 days of isolation on behavioral despair, anxiety-like behavior, and spatial working memory in adult male Wistar rats and found a substantial anxiolytic effect in the experimental (SI to EE) group. Interestingly, rats exposed to EE also showed increased behavioral despair compared with the control (continuous SI) group. There was no difference in spatial working memory performance at the end of a 5-day water Y-maze (WYM) test. However, the SI to EE animals displayed better memory performance in the first 2 days of the WYM, indicating faster learning. In line with this difference, we recorded significantly more c-Fos-immunopositive (c-Fos+) cells in the retrosplenial and perirhinal cortices of the SI to EE animals. The lateral and basolateral nuclei of the amygdala showed no such difference. These results suggest that brief enrichment following isolation stress leads to differential results in affective and cognitive systems.

Keywords: Elevated plus maze; Environmental enrichment; Forced swim test; Social isolation; Spatial memory; c-Fos.

To report the occurrence of non-ischemic cerebral enhancing (NICE) lesions following mechanical thrombectomy (MT) through the retrospective French nationwide registry of NICE lesions. All thrombectomy capable stroke centers (TSC) in France were invited to fill out a questionnaire disseminated through a trainee-led research network (JENI-RC: Jeunes en Neuroradiologie Interventionnelle-Research Collaborative). NICE lesions were defined according to previous literature as delayed onset punctate, nodular, or annular foci enhancements with peri-lesion edema and vascular distribution in the territory of the MT with no other confounding disease. All 43 TSC French centers responded. Three patients were reported by 3 different centers over a total of 34,824 MT (2015-2020). Patient no. 1 developed symptomatic NICE lesions 8 weeks after MT with combination of aspiration and stentriever for a right middle cerebral artery occlusion. Patient no. 2 developed asymptomatic NICE lesions 5 weeks after MT with direct thromboaspiration for a right middle cerebral artery occlusion. Patient no. 3 developed symptomatic NICE lesions 6 weeks after MT with direct thromboaspiration, and combination of aspiration and stentriever for a basilar artery occlusion. This study provides evidence that NICE lesions following MT are a possible rare complication with a similar presentation as previously described following endovascular aneurysm treatment. Both radiologists and neurologists should be aware of this adverse event and make use of MRI contrast agents in case of unexplained symptoms/images during follow-up after MT.

Keywords: Brain-enhancing lesions; Endovascular therapy; MRI; Mechanical thrombectomy; NICE; Stroke.

Objectives: The aim of this study was to assess the relationship between erosive tooth wear (ETW) and possible etiological factors in a group of dental students.

Materials and methods: A total of 126 dental students from a public dental school were included in this study. A questionnaire was used to investigate the possible etiological factors related to ETW. The Basic Erosive Wear Examination (BEWE) criteria were used to examine the status of ETW. A univariable and multivariable logistic regression models were used to assess the relationship between the presence of ETW and explanatory variables.

Results: Univariable analysis revealed that taking acidic foods and alcohol more than 4-5 times per week increases the odds of ETW by 6.043 and 2.532 times, respectively, and taking dairy products, fruit juice, and milk more than 4-5 times per week decreases the likelihood of ETW by 61%, 66%, and 80%, respectively. The results of multivariable regression analysis showed that the frequency of consumption of especially acidic foods significantly increased the risk of ETW (OR = 9.981, 95% CI 3.577-27.849, p < 0.001).

Conclusions: Although the ETW status of dental students, who are the future dentists, varies depending on different possible etiological factors, especially the consumption of acidic foods has increased the risk of ETW approximately 10 times.

Clinical relevance: The findings highlight the high relevance of ETW, especially with acidic food consumption, and the importance of controlling potential etiological factors in dental students.

Keywords: Dental erosion; Dental students; Erosive tooth wear; Prevention and control; Questionnaire.

Background: Children exposed to poverty and family adversities including domestic violence, parental mental ill health and parental alcohol misuse may experience poor outcomes across the life course. However, the complex interrelationships between these exposures in childhood are unclear. We therefore assessed the clustering of trajectories of household poverty and family adversities and their impacts on adolescent health outcomes.

Methods: We used longitudinal data from the UK Millennium Cohort study on 11564 children followed to age 14 years. Family adversities included parent reported domestic violence and abuse, poor mental health and frequent alcohol use. We used a group-based multi-trajectory cluster model to identify trajectories of poverty and family adversity for children. We assessed associations of these trajectories with child physical, mental and behavioural outcomes at age 14 years using multivariable logistic regression, adjusting for confounders.

Findings: Six trajectories were identified: low poverty and family adversity (43·2%), persistent parental alcohol use (7·7%), persistent domestic violence and abuse (3·4%), persistent poor parental mental health (11·9%), persistent poverty (22·6%) and persistent poverty and poor parental mental health (11·1%). Compared with children exposed to low poverty and adversity, children in the persistent adversity trajectory groups experienced worse outcomes; those exposed to persistent poor parental mental health and poverty were particularly at increased risk of socioemotional behavioural problems (adjusted odds ratio 6·4; 95% CI 5·0 - 8·3), cognitive disability (aOR 2·1; CI 1·5 - 2·8), drug experimentation (aOR 2·8; CI 1·8 - 4·2) and obesity (aOR 1·8; CI 1·3 - 2·5).

Interpretation: In a contemporary UK cohort, persistent poverty and/or persistent poor parental mental health affects over four in ten children. The combination of both affects one in ten children and is strongly associated with adverse child outcomes, particularly poor child mental health.

Funding: The National Institute for Health Research (NIHR) Policy Research Programme, NIHR Applied Research Collaboration South London (ARC South London) at King's College Hospital NHS Foundation Trust and the Medical Research Council (MRC).

Keywords: child health; child poverty; cohort; family adversity; multi-trajectory analysis.

Dermal delivery of bioactive molecules remains an attractive route of administration in osteoarthritis (OA) due to the local accumulation of drugs while avoiding their systemic side effects. In this study we propose a proniosome gel comprising non-ionic surfactants that self-assemble into de-hydrated vesicles for the delivery of the natural anti-inflammatory compound berberine. By modulating the hydrating ability of the proniosome gel, berberine can be efficiently released with minimal mechanical force. A combination of sorbitan oleate (S80) and polyethlene glycol sorbitan monolaurate (T20) in a sorbitan stearate (S60)-based proniosome enables a readily hydrated gel to deliver berberine into the skin, as confirmed by ex vivo skin permeation studies. Concurrently, an in vitro model of OA using primary mouse chondrocytes demonstrated that the release of berberine at a concentration as low as 1 μg mL^-1 is sufficient to restore the production of sulphated glycosaminoglycans (sGAG) to levels comparable to healthy chondrocytes while avoiding the cytotoxic concentrations (IC₅₀ = 33 μg mL^-1) on skin keratinocytes. In a mouse model of OA, the optimized formulation is able to attenuate inflammation and pain and minimize cartilage degeneration. Taken together, these data demonstrate the feasibility of adopting proniosome gels as a suitable platform to deliver active molecules for the management of osteoarthritis.

Objective: The COVID-19 pandemic has had potentially severe psychological implications for older adults, including those in retirement communities, due to restricted social interactions, but the day-to-day experience of loneliness has received limited study. We sought to investigate sequential association, if any, between loneliness, activity, and affect.

Methods: We used ecological momentary assessment (EMA) with dynamic network analysis to investigate the affective and behavioral concomitants of loneliness in 22 residents of an independent living sector of a continuing care retirement community (mean age 80.2; range 68-93 years).

Results: Participants completed mean 83.9% of EMA surveys (SD = 16.1%). EMA ratings of loneliness were moderately correlated with UCLA loneliness scale scores. Network models showed that loneliness was contemporaneously associated with negative affect (worried, anxious, restless, irritable). Negative (but not happy or positive) mood tended to be followed by loneliness and then by exercise or outdoor physical activity. Negative affect had significant and high inertia (stability).

Conclusions: The data suggest that EMA is feasible and acceptable to older adults. EMA-assessed loneliness was moderately associated with scale-assessed loneliness. Network models in these independent living older adults indicated strong links between negative affect and loneliness, but feelings of loneliness were followed by outdoor activity, suggesting adaptive behavior among relatively healthy adults.

Keywords: aging; causal networks; dynamic networks; loneliness; negative affect; positive affect; social isolation.

Aims and objectives: To establish an early warning model of hepatic encephalopathy in patients with liver cirrhosis based on psychological testing.

Methods: Data including patient demographics, number connection test-A (NCT-A), digit symbol test (DST), Model for End-Stage Liver Disease (MELD) scores were collected for patients admitted to a tertiary hospital in Shanghai with liver cirrhosis between January and December 2019. Patients were divided into two groups based on the development of hepatic encephalopathy (the hepatic encephalopathy group and non-hepatic encephalopathy group). Risk factors for hepatic encephalopathy in patients with liver cirrhosis were determined by using the binary logistic regression. We developed a predictive model in accordance with the STARD statement criteria (Supplementary File S1) with a cut-off value determined by receiver operating characteristic (ROC) curve analysis and calculation of the Youden index.

Results: A total of 417 patients with liver cirrhosis were included in the present study. Of these, 33 out of 66 patients with abnormal psychological tests had hepatic encephalopathy during hospitalisation. In contrast, 6 out of 317 patients with normal psychological tests had hepatic encephalopathy. Logistic regression analysis identified age, MELD score, and abnormal psychological tests as risk factors for hepatic encephalopathy in patients with liver cirrhosis. The area under the ROC curve for our prediction model for hepatic encephalopathy in patients with liver cirrhosis was 0.950 and the largest calculated Youden index was 0.804, which corresponds to a cut-off value is 0.0307.

Conclusion: Greater age, higher MELD score and abnormal psychological tests were significantly associated with increased risk of hepatic encephalopathy indicating early warning systems and identification of abnormal psychological tests are important components of the clinical nursing care process for cirrhotic patients. Our early warning model based on psychological testing can provide a basis for nursing observation and prevention of hepatic encephalopathy.

Relevance to clinical practice: Risk assessments for hepatic encephalopathy according to liver function and psychological tests, in addition to traditional neurological observations and dietary guidance, have utility in decreasing the incidence of hepatic encephalopathy.

Keywords: early warning model; hepatic encephalopathy; liver cirrhosis; nursing; psychological test.

Direct conver-sion of methane into value-added chemicals, such as methanol in mild conditions, is a promising route for industrial applications. In this work, atomically dispersed Rh on TiO2 suspended in the aqueous solution was used for the oxidation of methane to methanol. Promoted by copper cations (as co-catalyst) in solution, the catalysts exhibited high activity and selectivity for the production of methanol using molecular oxygen with the presence of carbon monoxide at 150 oC with a reaction pressure of 31 bar. Millimole level yields of methanol were reached with the selectivity higher than 99% using the Rh/TiO2 catalysts with the promotion of copper cation. CO was the reductive agent to generate H2 from H2O, which led to the formation of H2O2 through the reaction of H2 and O2. Atomically dispersed Rh activated the C-H bond in CH4 and catalyzed the oxidation using H2O2. Copper cations maintained the low-valence state of Rh. Moreover, copper acted as a scavenger for suppressing the overoxidation, thus leading to the high selectivity of methanol.

Keywords: methane, methanol, oxidation, copper, Rh catalyst.

Oner, an early-career researcher, and Lee and Sung, group leaders, have developed a deep learning model for accurate prediction of the proportion of cancer cells within tumor tissue. This is a necessary step for precision oncology and target therapy in cancer. They talk about their view of data science and the evolution of pathology in the coming years.

Purpose: This study identified factors predicting malignant upgrade for atypical ductal hyperplasia (ADH) diagnosed on core-needle biopsy (CNB) and developed a nomogram to facilitate evidence-based decision making.

Methods: This retrospective analysis included women diagnosed with ADH at the National Cancer Centre Singapore (NCCS) in 2010-2015. Cox proportional hazards regression was used to identify clinical, radiological, and histological factors associated with malignant upgrade. A nomogram was constructed using variables with the strongest associations in multivariate analysis. Multivariable logistic regression coefficients were used to estimate the predicted probability of upgrade for each factor combination.

Results: Between 2010 and 2015, 238,122 women underwent mammographic screening under the National Breast Cancer Screening Program. Among 29,564 women recalled, 5,971 CNBs were performed. Of these, 2,876 underwent CNBs at NCCS, with 88 patients (90 lesions) diagnosed with ADH and 26 lesions upgraded to breast malignancy on excision biopsy. In univariate analysis, factors associated with malignant upgrade were the presence of a mass on ultrasound (p = 0.018) or mammography (p = 0.026), microcalcifications (p = 0.047), diffuse microcalcification distribution (p = 0.034), mammographic parenchymal density (p = 0.008). and ≥ 3 separate ADH foci found on biopsy (p = 0.024). Mammographic parenchymal density (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.005-0.35; p = 0.014), presence of a mass on ultrasound (HR, 10.50; 95% CI, 9.21-25.2; p = 0.010), and number of ADH foci (HR, 1.877; 95% CI, 1.831-1.920; p = 0.002) remained significant in multivariate analysis and were included in the nomogram.

Conclusion: Our model provided good discrimination of breast cancer risk prediction (C-statistic of 0.81; 95% CI, 0.74-0.88) and selected for a subset of women at low risk (2.1%) of malignant upgrade, who may avoid surgical excision following a CNB diagnosis of ADH.

Keywords: Breast; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Nomograms; Prognosis.