Production of the antidepressant orcinol glucoside in Yarrowia lipolytica with yields over 6,400-fold higher than plant extraction.

Orcinol glucoside (OG), mainly found in the rhizome of the traditional Chinese herb Curculigo orchioides Gaertn, is noted for its antidepressant effects. In this study, an efficient screening pipeline was established for identifying the highly active orcinol synthase (ORS) and UDP-dependent glycosyltransferase (UGT) involved in the biosynthesis of OG by combining transcriptome analysis, structure-based virtual screening, and in vitro enzyme activity assays. By enhancing the downstream pathway, metabolic engineering and fermentation optimization, the OG production in Yarrowia lipolytica was improved 100-fold, resulting in a final yield of 43.46 g/L (0.84 g/g DCW), which is almost 6,400-fold higher than the extraction yield from C. orchioides roots. This study provides a reference for rapid identification of functional genes and high-yield production of natural products.

Unique composition of ocular surface microbiome in the old patients with dry eye and diabetes mellitus in a community from Shanghai, China.

BACKGROUND: This study investigates the variations in microbiome abundance and diversity on the ocular surfaces of diabetic patients suffering from dry eye within a community setting. The goal is to offer theoretical insights for the community-level prevention and treatment of dry eye in diabetic cohorts. METHODS: Dry eye screening was performed in the Shanghai Cohort Study of Diabetic Eye Disease (SCODE) from July 15, 2021, to August 15, 2021, in the Xingjing community; this study included both a population with diabetes and a normal population. The population with diabetes included a dry eye group (DM-DE, n = 40) and a non-dry eye group (DM-NoDE, n = 39). The normal population included a dry eye group (NoDM-DE, n = 40) and a control group (control, n = 39). High-throughput sequencing of the 16 S rRNA V3-V4 region was performed on conjunctival swab from both eyes of each subject, and the composition of microbiome on the ocular surface of each group was analyzed. RESULTS: Significant statistical differences were observed in both α and ß diversity of the ocular surface microbiome among the diabetic dry eye, diabetic non-dry eye, non-diabetic dry eye, and normal control groups (P < 0.05). CONCLUSIONS: The study revealed distinct microecological compositions on the ocular surfaces between the diabetic dry eye group and other studied groups. Firmicutes and Anoxybacillus were unique bacterial phyla and genera in the dry eye with DM group, while Actinobacteria and Corynebacterium were unique bacterial phyla and genera in the normal control group.

Evaluating imaging repeatability of fully self-service fundus photography within a community-based eye disease screening setting.

PURPOSE: This study aimed to investigate the imaging repeatability of self-service fundus photography compared to traditional fundus photography performed by experienced operators. DESIGN: Prospective cross-sectional study. METHODS: In a community-based eye diseases screening site, we recruited 65 eyes (65 participants) from the resident population of Shanghai, China. All participants were devoid of cataract or any other conditions that could potentially compromise the quality of fundus imaging. Participants were categorized into fully self-service fundus photography or traditional fundus photography group. Image quantitative analysis software was used to extract clinically relevant indicators from the fundus images. Finally, a statistical analysis was performed to depict the imaging repeatability of fully self-service fundus photography. RESULTS: There was no statistical difference in the absolute differences, or the extents of variation of the indicators between the two groups. The extents of variation of all the measurement indicators, with the exception of the optic cup area, were below 10% in both groups. The Bland-Altman plots and multivariate analysis results were consistent with results mentioned above. CONCLUSIONS: The image repeatability of fully self-service fundus photography is comparable to that of traditional fundus photography performed by professionals, demonstrating promise in large-scale eye disease screening programs.

Remnant cholesterol is correlated with retinal vascular morphology and diabetic retinopathy in type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: The association between remnant cholesterol (RC) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) remains unclear. Morphological changes in retinal vessels have been reported to predict vascular complications of diabetes, including DR. METHODS: This cross-sectional study included 6535 individuals with T2DM. The RC value was calculated using the recognized formula. The retinal vascular parameters were measured using fundus photography. The independent relationship between RC and DR was analyzed using binary logistic regression models. Multiple linear regression and subgroup analyses were employed to investigate the link between RC and vascular parameters, including the retinal arteriolar diameter (CRAE), venular diameter (CRVE), and fractal dimension (Df). Mediation analysis was performed to assess whether the vascular morphology could explain the association between RC and DR. RESULTS: RC was independently associated with DR in patients with a longer duration of T2DM (> 7 years). Patients with the highest quartile RC levels had larger CRAE (5.559 [4.093, 7.025] µm), CRVE (7.620 [5.298, 9.941] µm) and Df (0.013 [0.009, 0.017]) compared with patients with the lowest quartile RC levels. Results were robust across different subgroups. The association between RC and DR was mediated by CRVE (0.020 ± 0.005; 95% confidence interval: 0.012-0.032). CONCLUSIONS: RC may be a risk factor for DR among those who have had T2DM for a longer period of time. Higher RC levels were correlated with wider retinal arterioles and venules as well as higher Df, and it may contribute to DR through the dilation of retinal venules.

Langerhans cell histiocytosis in children with refractory diarrhoea and hypoalbuminaemia as the initial presentation: two case reports and a literature review.

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.

Service Quality and Residents' Preferences for Facilitated Self-Service Fundus Disease Screening: Cross-Sectional Study.

BACKGROUND: Fundus photography is the most important examination in eye disease screening. A facilitated self-service eye screening pattern based on the fully automatic fundus camera was developed in 2022 in Shanghai, China; it may help solve the problem of insufficient human resources in primary health care institutions. However, the service quality and residents' preference for this new pattern are unclear. OBJECTIVE: This study aimed to compare the service quality and residents' preferences between facilitated self-service eye screening and traditional manual screening and to explore the relationships between the screening service's quality and residents' preferences. METHODS: We conducted a cross-sectional study in Shanghai, China. Residents who underwent facilitated self-service fundus disease screening at one of the screening sites were assigned to the exposure group; those who were screened with a traditional fundus camera operated by an optometrist at an adjacent site comprised the control group. The primary outcome was the screening service quality, including effectiveness (image quality and screening efficiency), physiological discomfort, safety, convenience, and trustworthiness. The secondary outcome was the participants' preferences. Differences in service quality and the participants' preferences between the 2 groups were compared using chi-square tests separately. Subgroup analyses for exploring the relationships between the screening service's quality and residents' preference were conducted using generalized logit models. RESULTS: A total of 358 residents enrolled; among them, 176 (49.16%) were included in the exposure group and the remaining 182 (50.84%) in the control group. Residents' basic characteristics were balanced between the 2 groups. There was no significant difference in service quality between the 2 groups (image quality pass rate: P=.79; average screening time: P=.57; no physiological discomfort rate: P=.92; safety rate: P=.78; convenience rate: P=.95; trustworthiness rate: P=.20). However, the proportion of participants who were willing to use the same technology for their next screening was significantly lower in the exposure group than in the control group (P<.001). Subgroup analyses suggest that distrust in the facilitated self-service eye screening might increase the probability of refusal to undergo screening (P=.02). CONCLUSIONS: This study confirms that the facilitated self-service fundus disease screening pattern could achieve good service quality. However, it was difficult to reverse residents' preferences for manual screening in a short period, especially when the original manual service was already excellent. Therefore, the digital transformation of health care must be cautious. We suggest that attention be paid to the residents' individual needs. More efficient man-machine collaboration and personalized health management solutions based on large language models are both needed.

Preparation and Application of Degradable Lignin/Poly (Vinyl Alcohol) Polymers as Urea Slow-Release Coating Materials.

The massive amount of water-soluble urea used leads to nutrient loss and environmental pollution in both water and soil. The aim of this study was to develop a novel lignin-based slow-release envelope material that has essential nitrogen and sulfur elements for plants. After the amination reaction with a hydrolysate of yak hair keratin, the coating formulation was obtained by adding different loadings (2, 5, 8, 14 wt%) of aminated lignin (AL) to 5% polyvinyl alcohol (PVA) solution. These formulations were cast into films and characterized for their structure, thermal stability, and mechanical and physicochemical properties. The results showed that the PVA-AL (8%) formulation had good physical and chemical properties in terms of water absorption and mechanical properties, and it showed good degradation in soil with 51% weight loss after 45 days. It is suitable for use as a coating material for fertilizers. Through high-pressure spraying technology, enveloped urea particles with a PVA-AL (8%) solution were obtained, which showed good morphology and slow-release performance. Compared with urea, the highest urea release was only 96.4% after 30 days, conforming to Higuchi model, Ritger-Peppas model, and second-order dynamic model. The continuous nitrogen supply of PVA-AL coated urea to Brassica napus was verified by potting experiments. Therefore, the lignin-based composite can be used as a coating material to produce a new slow-release nitrogen fertilizer for sustainable crop production.

Mixed-phenotype (B-lymphocytic/myeloid) acute leukemia with ETV6-ABL1 expression.

Objectives: Mixed-phenotype acute leukemia (MPAL) is rare in the clinic, accounting for approximately 2%-5% of acute leukemia cases. Methods: In this study the cohort included 126 patients, of which 125 cases were from re-examined published data and current patients from Shenzhen Longhua District Central Hospital, carrying an ETV6-ABL1 rearrangement from April 15, 2020 to December 19, 2020. The ETS variant transcription factor 6-Abelson proto-oncogene 1 (ETV6-ABL1) fusion gene is mainly seen in malignant hematological diseases such as acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myeloproliferative neoplasms (MPNs). Positivity of both MPAL and ETV6-ABL1 suggest a poor prognosis. This is the first report of B lymphocytic/myeloid mixed-phenotype acute leukemia with ETV6-ABL1 fusion gene positivity. Complete remission was achieved with chemotherapy for lymphoid and myeloid leukemia and targeted therapy with tyrosine kinase inhibitors (TKIs). Results: The level of ETV6-ABL1/ABL decreased from 23.056% to 11.165%. After consolidation chemotherapy, the patient underwent allogeneic hematopoietic stem cell transplantation but died due to intestinal rejection. There are 126 cases of ETV6-ABL1 fusion gene transcript expression in numerous hematologic malignancies reported to date, including 48 cases of ALL, 12 of AML, and 65 of MPN. Eosinophilia is a common characteristic, especially in MPN patients. Conclusion: Survival analysis suggests that the survival time of ALL and MPN patients receiving TKI treatment is better than that of patients not receiving this treatment. Dasatinib or nilotinib, especially the former, is more effective than imatinib for MPN.

Loss-of-function variants within LMOD1 actin-binding site 2 cause pediatric intestinal pseudo-obstruction by impairing protein stability and actin nucleation.

The leiomodin1 (LMOD1) gene, encoding a potent actin nucleator, was recently reported as a potential pathogenic gene of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS, OMIM 619362). However, only a single patient has been reported to have LMOD1 mutations, and the underlying pathogenic mechanism remains unknown. Here, we described a male infant with LMOD1 mutations presenting typical symptoms of pediatric intestinal pseudo-obstruction (PIPO) but without megacystis and microcolon. Two compound heterozygous missense variants (c.1106C>T, p.T369M; c.1262G>A, p.R421H) were identified, both affecting highly conserved amino acid residues within the second actin-binding site (ABS2) domain of LMOD1. Expression analysis showed that both variants resulted in significantly reduced protein amounts, especially for p.T369M, which was almost undetectable. The reduction was only partially rescued by the proteasome inhibitor MG-132, indicating that there might be proteasome-independent pathways involved in the degradation of the mutant proteins. Molecular modeling showed that variant p.T369M impaired the local protein conformation of the ABS2 domain, while variant p.R421H directly impaired the intermolecular interaction between ABS2 and actin. Accordingly, both variants significantly damaged LMOD1-mediated actin nucleation. These findings provide further human genetic evidence supporting LMOD1 as a pathogenic gene underlying visceral myopathy including PIPO and MMIHS, strengthen the critical role of ABS2 domain in LMOD1-mediated actin nucleation, and moreover, reveal an unrecognized role of ABS2 in protein stability.

Systemic Inflammatory Biomarkers Predict Survival of Patients Treated With Tyrosine Kinase Inhibitors for Metastatic Renal Cell Carcinoma.

OBJECTIVE: We aimed to retrospectively investigate whether the neutrophil to lymphocyte ratio (NLR) and the monocyte to lymphocyte ratio (MLR) can predict the prognosis of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib or sorafenib. METHODS: We retrospectively identified 210 patients with mRCC treated with sunitinib or sorafenib from 2007 to 2017 at Fudan University- and Hexi University-affiliated hospitals. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate regression analysis was used to evaluate predictors of PFS and OS. RESULTS: Low NLR (<2.85) and MLR (<.30) were strongly associated with increased PFS and OS. Multivariable analyses verified that the NLR and MLR were both independent prognostic factors. Additionally, the NLR was negatively correlated with CD8+ and CD4+ T-cell infiltration in tumors. CONCLUSION: In patients with mRCC treated with sunitinib and sorafenib, an NLR <2.85 and MLR <.30 was associated with superior PFS and OS, which may be related to the reduced lymphocytic infiltration of tumors.

Evaluation of a new digital pediatric malnutrition risk screening tool for hospitalized children with congenital heart disease.

BACKGROUND: In a cohort of hospitalized children with congenital heart disease (CHD), a new digital pediatric malnutrition screening tool as a mobile application was validated, and its effectiveness and clinical value were determined as a prospective study. METHODS AND RESULTS: Children with CHD (n = 1125) were screened for malnutrition risk. The incidence of risk and the differences among various age groups and types of CHD were characterized. The optimal threshold for the tool to determine if there is a risk of malnutrition is score 2, while the Youden index was 79.1%, and the sensitivity and specificity were 91.2% and 87.9%, respectively. Based on such criterion, 351 children were at risk of malnutrition accounting for 31.20% of the total. Compared with the non-malnutritional risk group, the median age for the group at risk for malnutrition was younger (8.641 months [4.8, 23.1] vs. 31.589 months [12.4, 54.3], P < 0.01), and the length of stay was longer (12.000 [8.0, 17.0] vs. (8.420 [5.0, 12.0], P < 0.01]. There were significant differences in malnutrition risk among different age groups (χ2 = 144.933, P < 0.01), and children under one year of age exhibited the highest risk for malnutrition and more extended hospital stay (H = 78.085, P < 0.01). The risk of malnutrition among children with cyanotic CHD was higher than in those with non-cyanotic CHD (χ2 = 104.384, P < 0.01). CONCLUSIONS: The new digital pediatric malnutrition screening tool showed high sensitivity and specificity in children with CHD. The tool indicated that the malnutrition risk for young children and children with cyanotic or Bethesda moderate and complex CHD was higher, and the hospitalization time was longer than in the non-risk group. The tool provides a rational approach to targeted nutrition intervention and support and may improve clinical outcomes.

Computed tomography and magnetic resonance imaging for pulmonary embolus evaluation in children: up-to-date review on practical imaging protocols.

Pulmonary embolism (PE) is a potentially life-threatening condition that requires immediate medical intervention. Although PE was previously thought to occur infrequently in the pediatric population, recent studies have found a higher-than-expected prevalence of PE in the pediatric population of up to 15.5%. The imaging modality of choice for detecting PE in the pediatric population is multi-detector CT angiography, although MRI is assuming a growing and more important role as a potential alternative modality. Given the recent advances in both computed tomography pulmonary angiography (CTPA) and MRI techniques, a growing population of pediatric patients with complex comorbidities (such as children with a history of surgeries for congenital heart disease repair), and the recent waves of coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C), which are associated with increased risk of PE, there is new and increased need for an up-to-date review of practical CT and MRI protocols for PE evaluation in children. This article provides guidance for up-to-date CT and MR imaging techniques, reviews key recent studies on the imaging of pediatric PE, and discusses relevant pediatric PE imaging pearls and pitfalls, in hopes of providing readers with up-to-date and accurate practice for imaging evaluation of PE in children.

Perihilar cholangiocarcinoma resection: Is it beneficial for survival in elderly patients?

INTRODUCTION: As the population ages, surgeons are growing frequently faced with hard choices among a vast array of treatment options for the elderly. This study was to investigate safety and efficacy of resection in elderly patients with perihilar cholangiocarcinoma (PHCC). PATIENTS AND METHODS: Literature reading and meta-analysis unveiled that elderly PHCC patients held a higher risk of death within 90 days after hepatectomy relative to younger patients, but their 5-year overall survival and disease-free survival were comparable. Among PHCC patients who underwent hepatectomy, the proportion of elderly patients with tumor classification Bismuth I-II and tumor stage pStage 1-3 was significantly higher than that of younger patients. RESULTS: Curative resection R0 was more common in elderly patients than younger patients, but the difference was not statistically significant. Because of more comorbidities and less physiological reserve of elderly patients, they seemed to suffer more postoperative complications. CONCLUSION: Considering improved life expectancy, it is crucial to treat elderly PHCC patients appropriately and attempts should be made to radical surgery based on comorbidities and functional status.

A moderate dosage of coffee causes acute retinal capillary perfusion decrease in healthy young individuals.

AIM: Caffeinated beverages are very popular across populations and cultures, but quantitative evidence of the acute effects of moderate coffee doses on retinal perfusion is sparse and contradicting. Thus, the aim of this randomized, cross-over and parallel-group design study was to investigate whether moderate consumption of coffee alters macular retinal capillary perfusion in young healthy individuals. METHODS: Twenty-seven young healthy individuals were recruited for this study. Acute changes in retinal microvasculature were assessed using spectral-domain optical coherence tomography angiography (SD-OCTA) at baseline, 0.5 h, and 2 h after intake of coffee, or water. Meanwhile, cerebral blood flow (CBF) and retina-choroid blood flow were evaluated in a parallel-group design (4 participants each in coffee or water group) using magnetic resonance imaging (MRI) with pseudo-continuous arterial spin labeling sequences. RESULTS: Two hours after coffee intake, blood caffeine concentration increased from 0 to 5.05 ± 1.36 µg/mL. Coffee caused a significant decrease in retinal vessel diameter index (VDI) (19.05 ± 0.24 versus [vs] 19.13 ± 0.26; p < 0.001) and CBF in the frontal lobe (77.47 ± 15.21 mL/100 mL/min vs. 84.13 ± 15.55 mL/100 mL/min; p < 0.05) 2 h after intake. However, it significantly increased retina-choroid blood flow after 0.5 and 2 h (163.18 ± 61.07 mL/100 mL/min vs. 132.68 ± 70.47 mL/100 mL/min, p < 0.001, and 161.21 ± 47.95 vs. 132.68 ± 70.47; p < 0.001, respectively). CONCLUSION: This is the first study to demonstrate the acute effects of daily dose coffee consumption on retinal capillary perfusion using SD-OCTA combinate with blood flow MRI. The findings imply that although moderate coffee intake caused a significant increase in retina-choroid blood flow, there was a significant acute decrease both in macular retinal capillary perfusion and CBF.

Early Retinal Microvasculopathy in Prediabetic Patients and Correlated Factors.

INTRODUCTION: We aimed to detect early retinal microcirculation changes in prediabetic patients and investigate their correlation with clinical examinations. METHODS: Forty-seven prediabetic individuals, 29 controls, and 81 type 2 diabetic mellitus (T2DM) patients were enrolled in this study. A review of clinical data and spectral-domain optical coherence tomography angiography (SD-OCTA) parameters of macular vessel diameter (VD), foveal avascular zone (FAZ), and macular vessel area density (VAD) was performed. RESULTS: Levels of low-density lipoprotein cholesterol and triglycerides in prediabetes and T2DM groups were significantly higher than those in the control group. Urine microalbumin-to-creatinine ratio (ACR) was mildly and moderately increased in the prediabetes and T2DM groups, respectively. Estimated glomerular filtration rate of the three groups were within the normal range. SD-OCTA showed that VAD in the superficial macular area was decreased in the prediabetes group compared to the control group (p=0.01). The FAZ size, particularly in the deep layer, was expanded in the prediabetes group. In the deep retinal layer of the macular area, VD and FAZ size in the prediabetes group were larger than those in the control group. In the prediabetes group, the axial length was significantly correlated with macular VD and FAZ size (p<0.05), and ACR was correlated with FAZ size (p<0.05). Age had a negative correlation with VAD (p<0.01). ACR had a positive correlation with FAZ size (p<0.05). CONCLUSIONS: Enlargement and irregularity of the FAZ area, deep capillary dilation, and decrease in VAD occur in the retina of prediabetes patients with mild kidney function impairment.

Telescreening satisfaction: disparities between individuals with diabetic retinopathy and community health center staff.

BACKGROUND: The success of telescreening and the management of diabetic retinopathy (DR) in communities depends on stakeholder satisfaction, including both individuals with diabetes and community health center (CHC) staff. In this study, we investigated the satisfaction of both individuals with vision-threatening DR (VTDR) and CHC staff within the Shanghai Eye Disease Study (SEDS) comprehensive system for managing diabetic eye diseases at the primary care level. METHODS: The cross-sectional survey of patients receiving the service included 3,817 respondents with VTDR and focused on their satisfaction with the SEDS system, including the telescreening process, speed of feedback, interpretation of results, increased awareness of related diseases, and eye care services. The survey of the providers included 234 CHC staff respondents and focused on their satisfaction and the main barriers encountered during the implementation of the system. Sociodemographic characteristics and perceived barriers related to satisfaction were identified by conducting univariate and multivariate logistic regression analyses. RESULTS: The overall satisfaction of service recipients was 96.0%, and 75.8% of them were willing to undergo future telescreening for DR. The convenience of telescreening, organization of telescreening, and improvement in related disease awareness significantly correlated with satisfaction. Only 48.3% of the providers were satisfied with the SEDS system. The most frequently mentioned barriers to the development of the system were the inadequate levels of staffing (particularly technical staff), insufficient funding, and incomplete information transmission systems. CONCLUSIONS: Disparities between high patient satisfaction and low provider satisfaction with the SEDS system were mainly related to the current weak level of ophthalmic expertise in the CHCs and the low awareness of screening for diabetic eye diseases among both patients and providers.

Medical Staff and Resident Preferences for Using Deep Learning in Eye Disease Screening: Discrete Choice Experiment.

BACKGROUND: Deep learning-assisted eye disease diagnosis technology is increasingly applied in eye disease screening. However, no research has suggested the prerequisites for health care service providers and residents willing to use it. OBJECTIVE: The aim of this paper is to reveal the preferences of health care service providers and residents for using artificial intelligence (AI) in community-based eye disease screening, particularly their preference for accuracy. METHODS: Discrete choice experiments for health care providers and residents were conducted in Shanghai, China. In total, 34 medical institutions with adequate AI-assisted screening experience participated. A total of 39 medical staff and 318 residents were asked to answer the questionnaire and make a trade-off among alternative screening strategies with different attributes, including missed diagnosis rate, overdiagnosis rate, screening result feedback efficiency, level of ophthalmologist involvement, organizational form, cost, and screening result feedback form. Conditional logit models with the stepwise selection method were used to estimate the preferences. RESULTS: Medical staff preferred high accuracy: The specificity of deep learning models should be more than 90% (odds ratio [OR]=0.61 for 10% overdiagnosis; P<.001), which was much higher than the Food and Drug Administration standards. However, accuracy was not the residents' preference. Rather, they preferred to have the doctors involved in the screening process. In addition, when compared with a fully manual diagnosis, AI technology was more favored by the medical staff (OR=2.08 for semiautomated AI model and OR=2.39 for fully automated AI model; P<.001), while the residents were in disfavor of the AI technology without doctors' supervision (OR=0.24; P<.001). CONCLUSIONS: Deep learning model under doctors' supervision is strongly recommended, and the specificity of the model should be more than 90%. In addition, digital transformation should help medical staff move away from heavy and repetitive work and spend more time on communicating with residents.

Multiplex network disintegration strategy inference based on deep network representation learning.

Multiplex networks have attracted more and more attention because they can model the coupling of network nodes between layers more accurately. The interaction of nodes between layers makes the attack effect on multiplex networks not simply a linear superposition of the attack effect on single-layer networks, and the disintegration of multiplex networks has become a research hotspot and difficult. Traditional multiplex network disintegration methods generally adopt approximate and heuristic strategies. However, these two methods have a number of drawbacks and fail to meet our requirements in terms of effectiveness and timeliness. In this paper, we develop a novel deep learning framework, called MINER (Multiplex network disintegration strategy Inference based on deep NEtwork Representation learning), which transforms the disintegration strategy inference of multiplex networks into the encoding and decoding process based on deep network representation learning. In the encoding process, the attention mechanism encodes the coupling relationship of corresponding nodes between layers, and reinforcement learning is adopted to evaluate the disintegration action in the decoding process. Experiments indicate that the trained MINER model can be directly transferred and applied to the disintegration of multiplex networks with different scales. We extend it to scenarios that consider node attack cost constraints and also achieve excellent performance. This framework provides a new way to understand and employ multiplex networks.

A Generic Pixel Pitch Calibration Method for Fundus Camera via Automated ROI Extraction.

Pixel pitch calibration is an essential step to make the fundus structures in the fundus image quantitatively measurable, which is important for the diagnosis and treatment of many diseases, e.g., diabetes, arteriosclerosis, hereditary optic atrophy, etc. The conventional calibration approaches require the specific parameters of the fundus camera or several specially shot images of the chess board, but these are generally not accessible, and the calibration results cannot be generalized to other cameras. Based on automated ROI (region of interest) and optic disc detection, the diameter ratio of ROI and optic disc (ROI-disc ratio) is quantitatively analyzed for a large number of fundus images. With the prior knowledge of the average diameter of an optic disc in fundus, the pixel pitch can be statistically estimated from a large number of fundus images captured by a specific camera without the availability of chess board images or detailed specifics of the fundus camera. Furthermore, for fundus cameras of FOV (fixed field-of-view), the pixel pitch of a fundus image of 45° FOV can be directly estimated according to the automatically measured diameter of ROI in the pixel. The average ROI-disc ratio is approximately constant, i.e., 6.404 ± 0.619 in the pixel, according to 40,600 fundus images, captured by different cameras, of 45° FOV. In consequence, the pixel pitch of a fundus image of 45° FOV can be directly estimated according to the automatically measured diameter of ROI in the pixel, and results show the pixel pitches of Canon CR2, Topcon NW400, Zeiss Visucam 200, and Newvision RetiCam 3100 cameras are 6.825 ± 0.666 µm, 6.625 ± 0.647 µm, 5.793 ± 0.565 µm, and 5.884 ± 0.574 µm, respectively. Compared with the manually measured pixel pitches, based on the method of ISO 10940:2009, i.e., 6.897 µm, 6.807 µm, 5.693 µm, and 6.050 µm, respectively, the bias of the proposed method is less than 5%. Since our method doesn't require chess board images or detailed specifics, the fundus structures on the fundus image can be measured accurately, according to the pixel pitch obtained by this method, without knowing the type and parameters of the camera.

Efficacy and safety of parenteral nutrition with iron sucrose for anemia prevention in preterm infants: A randomized, double-blind controlled study.

BACKGROUND AND OBJECTIVES: Our objective is to study the efficacy and safety of parenteral nutrition (PN) with iron sucrose to prevent anemia in preterm infants. METHODS AND STUDY DESIGN: We performed a randomized, double-blind controlled trial in which preterm infants were divided into five groups randomly: a control group (PN without iron sucrose, namely group Iron-0), and intervention groups (PN with iron sucrose 100 µg/kg/d, 200 µg/kg/d, 300 µg/kg/d and 400 µg/kg/d, namely group Iron-1, 2, 3, and 4, respectively). The indicators were red blood cell (RBC) parameters, iron storage and oxidant stress. RESULTS: One hundred infants completed this study. Excepting the RBC count in Iron-2, the value of erythrocyte parameters in intervention groups decreased less than that in the control group. And the decrease of RBC count in Iron-1 (-0.6×1012/L vs -0.9×1012/L, p=0.033), hemoglobin in Iron-4 (-26.0 g/L vs -41.0 g/L, p=0.03) and hematocrit in Iron-1(-9.5% vs -14.0%, p=0.014) was significantly less than in the control group. The change of ferritin in Iron-4 was significantly higher than in the control group (280 ng/ml vs 118 ng/ml, p=0.04). There was no difference in serum iron in intervention groups when compared to the control group (p>0.05). Except for the change of malondialdehyde (MDA) in Iron-1, the increase in other intervention groups was higher than in the control group (p>0.05). CONCLUSIONS: PN with iron sucrose for prevention of anemia in preterm infants is safe and efficacious to some extent.