Ecological and functional differences of abundant and rare sub-communities in wastewater treatment plants across China.

The microbial community in activated sludge is composed of a small number of abundant sub-community with high abundance and a large number of rare sub-community with limited abundance. Our knowledge regarding the ecological properties of both abundant and rare sub-communities in activated sludge is limited. This article presented an analysis of functional prediction, assembly mechanisms, and biogeographic distribution characteristics of abundant and rare sub-communities in 211 activated sludge samples from 60 wastewater treatment plants across China. Moreover, this study investigated the dominant factors influencing the community structure of these two microbial groups. The results showed that the functions associated with carbon and nitrogen cycling were primarily detected in abundant sub-community, while rare sub-community were primarily involved in sulfur cycling. Both microbial groups were mainly influenced by dispersal limitation, which, to some extent, resulted in a distance-decay relationship in their biogeographic distribution. Moreover, a higher spatial turnover rate of rare sub-communities (0.0887) suggested that spatial differences in microbial community structure among different WWTPs may mainly result from rare sub-community. Moreover, SEM showed that geographic locations affected rare sub-communities greatly, which agreed with their higher dispersal limitation and turnover rate. In contrast, influent characteristics showed stronger correlations with abundant sub-communities, suggesting that abundant sub-community may contribute more to the removal of pollutants. This study enhanced our understanding of abundant and rare microorganisms in activated sludge especially the role of rare species and provided scientific evidence for precise regulation and control of wastewater treatment plants.

The potential of ferrihydrite-synthetic humic-like acid composite as a soil amendment for metal-contaminated agricultural soil: Immobilization mechanisms by combining abiotic and biotic perspectives.

In-situ passivation technique has attracted increasing attention for metal-contaminated agricultural soil remediation. However, metal immobilization mechanisms are mostly illustrated based on metal speciation changes and alterations in soil physicochemical properties from a macroscopic and abiotic perspective. In this study, a ferrihydrite-synthetic humic-like acid composite (FH-SHLA) was fabricated and applied as a passivator for a 90-day soil incubation. The heavy metals immobilization mechanisms of FH-SHLA were investigated by combining both abiotic and biotic perspectives. Effects of FH-SHLA application on soil micro-ecology were also evaluated. The results showed that the 5%FH-SHLA treatment significantly decreased the DTPA-extractable Pb, Cd and Zn by 80.75%, 46.82% and 63.63% after 90 days of incubation (P < 0.05), respectively. Besides, 5% FH-SHLA addition significantly increased soil pH, soil organic matter content and cation exchange capacity (P < 0.05). The SEM, FTIR, and XPS characterizations revealed that the abiotic metal immobilization mechanisms by FH-SHLA included surface complexation, precipitation, electrostatic attraction, and cation-π interactions. For biotic perspective, in-situ microorganisms synergistically participated in the immobilization process via sulfide precipitation and Fe mineral production. FH-SHLA significantly altered the diversity and composition of the soil microbial community, and enhanced the intensity and complexity of the microbial co-occurrence network. Both metal bioavailability and soil physiochemical parameters played a vital role in shaping microbial communities, while the former contributed more. Overall, this study provides new insight into the heavy metal passivation mechanism and demonstrates that FH-SHLA is a promising and environmentally friendly amendment for metal-contaminated soil remediation.

Neuromodulation and Functional Gastrointestinal Disease.

INTRODUCTION: Functional gastrointestinal disorders (FGIDs) are common, and they severely impair an individual's quality of life. The mechanism of pathogenesis and the effective treatments for FGIDs remain elusive. Neuromodulation-a relatively new treatment-has exhibited a good therapeutic effect on FGIDs, although there are different methods for different symptoms of FGIDs. MATERIALS AND METHODS: We used PubMed to review the history of neuromodulation for the treatment of FGIDs and to review several recently proposed neuromodulation approaches with improved effects on FGIDs. CONCLUSION: Electroacupuncture, transcutaneous electroacupuncture, transcutaneous auricular vagal nerve stimulation, sacral nerve stimulation (SNS) (which relies on vagal nerve stimulation), and gastric electrical stimulation (which works through the modulation of slow waves generated by the interstitial cells of Cajal), in addition to the noninvasive neurostimulation alternative approach method of SNS-tibial nerve stimulation and transcutaneous electrical stimulation (which is still in its infancy), are some of the proposed neuromodulation approaches with improved effects on FGIDs. This review has discussed some critical issues related to the selection of stimulation parameters and the underlying mechanism and attempts to outline future research directions backed by the existing literature.

Predictors of hospital-acquired pressure injuries in patients with complete spinal cord injury: a retrospective case-control study.

BACKGROUND: Despite current best practices, pressure injuries (PI) remain a devastating and prevalent hospital-acquired complication for patients with acute traumatic spinal cord injuries (SCIs). This study examined associations between risk factors for PI development in patients with complete SCI, such as norepinephrine dose and duration, and other demographic factors or lesion characteristics. METHODS: This case-control study included adults with acute complete SCIs ASIA-A, who were admitted to a level-one trauma center between 2014-18. A retrospective review was implement using data on patient and injury characteristics, including age, gender, level of SCI (cervical vs. thoracic), Injury Severity Score (ISS), length of stay (LOS) and mortality; presence/absence of PI during their acute hospital stay; and treatment factors such as spinal surgery, mean arterial pressure (MAP) targets, and vasopressor treatment. Multivariable logistic regression evaluated associations with PI. RESULTS: Eighty-two out of 103 eligible patients had complete data, and 30 (37%) developed PIs. Patient and injury characteristics, including age (Mean: 50.6; SD:21.3), location of SCI (48 cervical, 59%) and ISS (Mean 33.1; SD:11.8), did not differ between PI and non-PI groups. Logistic regression analysis revealed that male gender (OR:34.1; CI95:2.3-506.5, p = 0.010) and increased LOS (log-transformed; OR:20.5, CI95:2.8-149.9, p = 0.003) were associated with increased risk of PI. Having an order for a MAP > 80mmg (OR:0.05; CI95:0.01-0.30, p = 0.001) was associated with a reduced risk of PI. There were no significant associations between PI and duration of norepinephrine treatment. CONCLUSIONS: Norepinephrine treatment parameters were not associated with development of PI, suggesting that MAP targets should be a focus for future investigations for SCI management. Increasing LOS should highlight the need for high-risk PI prevention and vigilance.

Catalyzing dementia care through the learning health system and consumer health information technology.

To advance care for persons with Alzheimer's disease and related dementias (ADRD), real-world health system effectiveness research must actively engage those affected to understand what works, for whom, in what setting, and for how long-an agenda central to learning health system (LHS) principles. This perspective discusses how emerging payment models, quality improvement initiatives, and population health strategies present opportunities to embed best practice principles of ADRD care within the LHS. We discuss how stakeholder engagement in an ADRD LHS when embedding, adapting, and refining prototypes can ensure that products are viable when implemented. Finally, we highlight the promise of consumer-oriented health information technologies in supporting persons living with ADRD and their care partners and delivering embedded ADRD interventions at scale. We aim to stimulate progress toward sustainable infrastructure paired with person- and family-facing innovations that catalyze broader transformation of ADRD care.

Sodium Carbazolide and Derivatives as Solid-State Electrolytes for Sodium-Ion Batteries.

Replacing widely used organic liquid electrolytes with solid-state electrolytes (SSEs) could effectively solve the safety issues in sodium-ion batteries. Efforts on seeking novel solid-state electrolytes have been continued for decades. However, issues about SSEs still exist, such as low ionic conductivity at ambient temperature, difficulty in manufacturing, low electrochemical stability, poor compatibility with electrodes, etc. Here, sodium carbazolide (Na-CZ) and its THF-coordinated derivatives are rationally fabricated as Na+ conductors, and two of their crystal structures are successfully solved. Among these materials, THF-coordinated complexes exhibit fast Na+ conductivities, i.e., 1.20×10-4  S cm-1 and 1.95×10-3  S cm-1 at 90 °C for Na-CZ-1THF and Na-CZ-2THF, respectively, which are among the top Na+ conductors under the same condition. Furthermore, stable Na plating/stripping is observed even over 400 h cycling, showing outstanding interfacial stability and compatibility against Na electrode. More advantages such as ease of synthesis, low-cost, and cold pressing for molding can be obtained. In situ NMR results revealed that the evaporation of THF may play an essential role in the Na+ migration, where the movement of THF creates defects/vacancies and facilitates the migration of Na+ .

Burnout and the role of authentic leadership in academic medicine.

BACKGROUND: Recently, there has been increasing evidence that reducing burnout in healthcare providers requires significant organizational efforts that include the integration of leadership strategies. METHODS: Focus groups were conducted across four health systems within the University of Colorado Department of Medicine in four affinity groups (administrative staff, medical trainees, research faculty, and clinical faculty). Authentic leadership theory was used for analysis to advance the understanding of the role of leadership style upon participants' work experiences and preferences, and to identify opportunities for translation of site-specific results to other academic medical settings. RESULTS: Study participants from each affinity group believed their clinical leaders lacked objectivity with decision-making (lacking "balancing processing"), which contributed to their overall feeling of powerlessness. The experience of increasing work demands was salient throughout all twelve focus groups, and participants identified leadership that interacted in a more open and self-disclosing manner ("relational transparency") as alleviating at least some of this burden. Strong preference discernable alignment between their leaders' decision-making and their internal moral compass of values (demonstrating "internalized moral perspective") was described, as was clinical leaders demonstrating "self-awareness" (having a self-reflective process that informs the leader's decision-making). Comparing affinity group experiences within each authentic leadership theory construct identified the relevance of contextual factors, such as work setting and roles, upon employees' perceptions and expectations of their leaders. CONCLUSIONS: Use of authentic leadership theory advanced the understanding of the association between leadership traits and experiences of burnout amongst a large group of academic clinicians, researchers, trainees, and administrative staff. Leadership styles that promoted relationship transparency, openness, and support were preferred and fostering these traits may help address the demands in academic medicine, including symptoms of burnout.

Mediators of SARS-CoV-2 entry are preferentially enriched in cardiomyocytes.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has spread rapidly around the world. In addition to common respiratory symptoms such as cough and fever, some patients also have cardiac injury, however, the mechanism of cardiac injury is not clear. In this study, we analyzed the RNA expression atlases of angiotensin-converting enzyme 2(ACE2), cathepsin B (CTSB) and cathepsin L (CTSL) in the human embryonic heart at single-cell resolution. RESULTS: The results showed that ACE2 was preferentially enriched in cardiomyocytes. Interestingly, serine protease transmembrane serine protease 2 (TMPRSS2) had less expression in cardiomyocytes, but CTSB and CTSL, which belonged to cell protease, could be found to be enriched in cardiomyocytes. The results of enrichment analysis showed that differentially expressed genes (DEGs) in ACE2-positive cardiomyocytes were mainly enriched in the processes of cardiac muscle contraction, regulation of cardiac conduction, mitochondrial respiratory chain, ion channel binding, adrenergic signaling in cardiomyocytes and viral transcription. CONCLUSIONS: Our study suggests that both atrial and ventricular cardiomyocytes are potentially susceptible to severe acute respiratory syndrome coronavirus-2(SARS-CoV-2), and SARS-CoV-2 may enter ventricular cardiomyocytes using CTSB/CTSL for S protein priming. This may be the partial cellular mechanism of cardiac injury in patients with COVID-19.

Patients Contributing to Visit Notes: Mixed Methods Evaluation of OurNotes.

BACKGROUND: Secure patient portals are widely available, and patients use them to view their electronic health records, including their clinical notes. We conducted experiments asking them to cogenerate notes with their clinicians, an intervention called OurNotes. OBJECTIVE: This study aims to assess patient and provider experiences and attitudes after 12 months of a pilot intervention. METHODS: Before scheduled primary care visits, patients were asked to submit a word-constrained, unstructured interval history and an agenda for what they would like to discuss at the visit. Using site-specific methods, their providers were invited to incorporate the submissions into notes documenting the visits. Sites served urban, suburban, and rural patients in primary care practices in 4 academic health centers in Boston (Massachusetts), Lebanon (New Hampshire), Denver (Colorado), and Seattle (Washington). Each practice offered electronic access to visit notes (open notes) to its patients for several years. A mixed methods evaluation used tracking data and electronic survey responses from patients and clinicians. Participants were 174 providers and 1962 patients who submitted at least 1 previsit form. We asked providers about the usefulness of the submissions, effects on workflow, and ideas for the future. We asked patients about difficulties and benefits of providing the requested information and ideas for future improvements. RESULTS: Forms were submitted before 9.15% (5365/58,652) eligible visits, and 43.7% (76/174) providers and 26.76% (525/1962) patients responded to the postintervention evaluation surveys; 74 providers and 321 patients remembered receiving and completing the forms and answered the survey questions. Most clinicians thought interim patient histories (69/74, 93%) and patient agendas (72/74, 97%) as good ideas, 70% (52/74) usually or always incorporated them into visit notes, 54% (40/74) reported no change in visit length, and 35% (26/74) thought they saved time. Their most common suggestions related to improving notifications when patient forms were received, making it easier to find the form and insert it into the note, and educating patients about how best to prepare their submissions. Patient respondents were generally well educated, most found the history (259/321, 80.7%) and agenda (286/321, 89.1%) questions not difficult to answer; more than 92.2% (296/321) thought sending answers before the visit a good idea; 68.8% (221/321) thought the questions helped them prepare for the visit. Common suggestions by patients included learning to write better answers and wanting to know that their submissions were read by their clinicians. At the end of the pilot, all participating providers chose to continue the OurNotes previsit form, and sites considered expanding the intervention to more clinicians and adapting it for telemedicine visits. CONCLUSIONS: OurNotes interests patients, and providers experience it as a positive intervention. Participation by patients, care partners, clinicians, and electronic health record experts will facilitate further development.

ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) patients have relatively poor clinical outcomes. A marker predicting the prognosis of patients with TNBC could help guide treatment. Extensive evidence demonstrates that angiopoietin-like 4 (ANGPTL4) is involved in the regulation of cancer growth, metastasis and angiogenesis. Therefore, its role in TNBC is of interest. METHODS: We tested the ANGPTL4 expression level in tumor tissues by immunohistochemistry (IHC) and detected its association with the clinical features of TNBC patients. Next, the effects and mechanisms of ANGPTL4 on TNBC cell migration and adhesion were investigated. RESULTS: We found that ANGPTL4 overexpression was associated with favorable outcomes in TNBC patients. ANGPTL4 upregulation inhibited cell adhesion, migration and invasion in vitro. Further analyses demonstrated that the possible mechanism might involve suppression of TNBC progression by interacting with extracellular matrix-related genes. CONCLUSIONS: The present findings demonstrated that enhancement of ANGPTL4 expression might inversely correlate with TNBC progression. ANGPTL4 is a promising marker of TNBC and should be evaluated in further studies. TRIAL REGISTRATION: Retrospectively registered.

Advance Care Planning Among Users of a Patient Portal During the COVID-19 Pandemic: Retrospective Observational Study.

BACKGROUND: Advance care planning is the process of discussing health care treatment preferences based on patients' personal values, and it often involves the completion of advance directives. In the first months of 2020, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began circulating widely in the American state of Colorado, leading to widespread diagnosis of coronavirus disease (COVID-19), hospitalizations, and deaths. In this context, the importance of technology-based, non-face-to-face methods to conduct advance care planning via patient portals has increased. OBJECTIVE: The aim of this study was to determine the rates of use of a web-based advance care planning tool through a health system-based electronic patient portal both before and in the early months of the COVID-19 pandemic. METHODS: In 2017, we implemented web-based tools through the patient portal of UCHealth's electronic health record (EHR) for patients to learn about advance care planning and complete an electronically signed medical durable power of attorney (MDPOA) to legally appoint a medical decision maker. Patients accessing the portal can complete and submit a legally valid MDPOA, which becomes part of their medical record. We collected data on the patients' date of MDPOA completion, use of advance care planning messaging, age, sex, and geographic location during the early phase of the COVID-19 pandemic (December 29, 2019, to May 30, 2020). RESULTS: Over a 5-month period that includes the early phase of the COVID-19 pandemic in Colorado, total monthly use of the advance care planning portal tool increased from 418 users in January to 1037 users in April and then decreased slightly to 815 users in May. The number of MDPOA forms submitted per week increased 2.4-fold after the stay-at-home order was issued in Colorado on March 26, 2020 (P<.001). The mean age of the advance care planning portal users was 47.7 years (SD 16.1), and 2206/3292 (67.0%) were female. Women were more likely than men to complete an MDPOA, particularly in younger age groups (P<.001). The primary use of the advance care planning portal tools was the completion of an MDPOA (3138/3292, 95.3%), compared to sending an electronic message (148/3292, 4.5%). Over 50% of patients who completed an MDPOA did not have a prior agent in the EHR. CONCLUSIONS: Use of a web-based patient portal to complete an MDPOA increased substantially during the first months of the COVID-19 pandemic in Colorado. There was an increase in advance care planning that corresponded with state government shelter-in-place orders as well as public health reports of increased numbers of COVID-19 cases and deaths. Patient portals are an important tool for providing advance care planning resources and documenting medical decision makers during the pandemic to ensure that medical treatment aligns with patient goals and values.

Integrating the Practical Robust Implementation and Sustainability Model With Best Practices in Clinical Decision Support Design: Implementation Science Approach.

BACKGROUND: Clinical decision support (CDS) design best practices are intended to provide a narrative representation of factors that influence the success of CDS tools. However, they provide incomplete direction on evidence-based implementation principles. OBJECTIVE: This study aims to describe an integrated approach toward applying an existing implementation science (IS) framework with CDS design best practices to improve the effectiveness, sustainability, and reproducibility of CDS implementations. METHODS: We selected the Practical Robust Implementation and Sustainability Model (PRISM) IS framework. We identified areas where PRISM and CDS design best practices complemented each other and defined methods to address each. Lessons learned from applying these methods were then used to further refine the integrated approach. RESULTS: Our integrated approach to applying PRISM with CDS design best practices consists of 5 key phases that iteratively interact and inform each other: multilevel stakeholder engagement, designing the CDS, design and usability testing, thoughtful deployment, and performance evaluation and maintenance. The approach is led by a dedicated implementation team that includes clinical informatics and analyst builder expertise. CONCLUSIONS: Integrating PRISM with CDS design best practices extends user-centered design and accounts for the multilevel, interacting, and dynamic factors that influence CDS implementation in health care. Integrating PRISM with CDS design best practices synthesizes the many known contextual factors that can influence the success of CDS tools, thereby enhancing the reproducibility and sustainability of CDS implementations. Others can adapt this approach to their situation to maximize and sustain CDS implementation success.

ALDH2 Gene rs671 Polymorphism May Decrease the Risk of Essential Hypertension.

Aldehyde dehydrogenase-2 (ALDH2) rs671 G>A polymorphism can influence the activity of ALDH2 and may be associated with the risk of essential hypertension (EH). Although many previous studies have explored such a relationship, the conclusion is still controversial.The PubMed, Embase, and China National Knowledge Infrastructure databases were searched on the ALDH2 gene and EH. We used the Newcastle-Ottawa Scale to evaluate the quality of the study. Then we calculated the strength of relationship between ALDH2 rs671 mutation and EH by utilizing odds ratios and 95% confidence intervals. Besides, subgroup analysis and sensitivity analysis were performed and the publication bias was assessed.There were 12 studies containing 8153 cases and 10,162 controls. Our meta-analysis showed significant association between ALDH2 rs671 polymorphism and EH in four genetic models (the allele model, the homozygote model, the heterozygote model, and the dominant model), whereas it did not indicate this connection in the recessive model. However, a trend of decreased risk still could be seen. Furthermore, we also found an obvious association between rs671 mutation and the risk of EH in the male group than in the female group in all five genetic models.We concluded that ALDH2 rs671 G>A polymorphism may decrease the risk of EH. Furthermore, susceptibility to EH reduced in males but not in females. As a variant in ALDH2, rs671 G>A could be an attractive candidate for genetic therapy of EH. In addition, more case-control studies should be conducted to strengthen our conclusion and evaluate the gene-gene and gene-environment interactions between the ALDH2 gene and EH.

Association Between MTHFR C677T Polymorphism and Congenital Heart Disease.

Many published studies have evaluated the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) polymorphism and the risk of congenital heart disease (CHD); however, the specific conclusion is still controversial.To get a more accurate conclusion, we used a meta-analysis to evaluate the association between the MTHFR gene C677T polymorphism and the risk of CHD.Based on the design-based search strategy, a comprehensive literature search was conducted on PubMed, OVID, Cochrane Library, Embase, Wanfang, CNKI, and Web of Science. We selected the Newcastle-Ottawa Scale (NOS) to assess the quality of the included studies. We performed a heterogeneity test on the results of the study and calculated the combined odds ratios (ORs) and its corresponding 95% confidence intervals (95% CIs) under a random- or fixed-effect model. Subgroup analyses were conducted by ethnicity, source of controls, sample size, and genotyping method. Sensitivity analysis was used to insure authenticity of this meta-analysis result. Egger's test and Begg's funnel plot were performed to detect publication bias.Eventually, our meta-analysis included 15 eligible studies. We observed a significant correlation between the MTHFR C677T polymorphism and the development of CHD in the recessive model (OR: 1.35, 95% CI: 1.06-1.71, P = 0.006) for the overall population. In subgroups stratified by ethnicity and source of controls, subgroup analyses indicated similar associations in Asians and hospital-based groups, but not for Caucasians and population-based groups. Egger's test and Begg's funnel plot demonstrated no significant publication bias in our study.Our analysis identified that MTHFR C677T allele is a risk genetic for CHD development, especially in Asians compared with Caucasians.

Evaluation of acute myocardial infarction patients with mid-range ejection fraction after emergency percutaneous coronary intervention.

BACKGROUND: There is currently no classification for acute myocardial infarction (AMI) according to left ventricular ejection fraction (LVEF). We aimed to perform a retrospective analysis of patients undergoing emergency percutaneous coronary intervention (PCI), comparing the clinical characteristics, in-hospital acute heart failure and all-cause death events of AMI patients with mid-range ejection fraction (mrEF), preserved ejection fraction (pEF) and reduced ejection fraction (rEF). MATERIAL AND METHODS: Totally 1270 patients were stratified according to their LVEF immediately after emergency PCI into pEF group (LVEF 50% or higher), mrEF group (LVEF 40%-49%) and rEF group (LVEF <40%). Kaplan-Meier curves and log rank tests were used to assess the effects of mrEF, rEF and pEF on the occurrence of acute heart failure and all-cause death during hospitalisation. The Cox proportional hazards model was used for multivariate correction. RESULTS: Compared with mrEF, rEF was an independent risk factor for acute heart failure events during hospitalisation (HR 5.01, 95% CI 3.53 to 7.11, p<0.001), and it was also an independent risk factor for all-cause mortality during hospitalisation (HR 7.05, 95% CI 4.12 to 12.1, p<0.001); Compared with mrEF, pEF was an independent protective factor for acute heart failure during hospitalisation (HR 0.49, 95% CI 0.30 to 0.82, p=0.01), and it was also an independent protective factor for all-cause death during hospitalisation (HR 0.33, 95% CI 0.11 to 0.96, p=0.04). CONCLUSIONS: mrEF patients with AMI undergoing emergency PCI share many similarities with pEF patients in terms of clinical features, but the prognosis is significantly worse than that of pEF patients, suggesting that we need to pay attention to the management of mrEF patients with AMI.

Patient Attitudes About Viewing Their Radiology Images Online: Preintervention Survey.

BACKGROUND: Although patient data is available through electronic portals, little information exists about the benefits and/or challenges of providing patients with online access to their radiology images. OBJECTIVE: The aims of this quality improvement project were to understand patient attitudes toward being able to view their radiology images online and determine how information should be presented to ensure the images are helpful to the patients, rather than causing confusion and anxiety. METHODS: An online survey of consumers was conducted to evaluate attitudes toward online access to personal radiological images. RESULTS: A total of 105 responses were received from 686 community members (15.3%). Of 105 consumers, 94 (89.5%) reported a desire to have access to the radiology images within their online patient portal; 86.7% (91/105) believed it would help them better understand their medical conditions and 81.0% (85/105) said this would help them feel more in control of their care. Most respondents (74/105, 70.5%) said it would help them feel reassured that their doctor was doing the right thing, and 63.8% (67/105) said it would increase their level of trust in their doctor. Among surveyed patients, 78.1% (82/105) valued viewing their radiology images online, while 92.4% (97/105) valued their online radiology reports. Most patients (69/105, 65.7%) wished to discuss their results with their ordering clinician, 29.5% (31/105) wished to discuss with their interpreting radiologist, and 3.8% (4/105) wished to share their images on social media. The biggest potential concern among 23.8% (25/105) was that the images would be confusing. CONCLUSIONS: A large majority of surveyed patients desired the ability to view their radiology images online and anticipated many benefits and few risks. Health care organizations with electronic health records and online patient portals should consider augmenting their existing portals with this highly desired feature. To avoid the biggest patient concern, radiology reports should accompany images. Patients wanted to discuss their results with their ordering physician and their interpreting radiologist. Some even would like to share results on social media. Further research on the actual experience with such a tool will be needed.

Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody.

Enterovirus 71 (EV71) is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM) single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3) of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2), the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection.

Morphological, Stability, and Hypoglycemic Effects of New Gliclazide-Bile Acid Microcapsules for Type 1 Diabetes Treatment: the Microencapsulation of Anti-diabetics Using a Microcapsule-Stabilizing Bile Acid.

When we administered orally a mixture of the anti-diabetic drug, gliclazide (G) and a primary bile acid, they exerted a hypoglycemic effect in a rat model of type 1 diabetes (T1D), but stability of mixture was limited. We aimed to develop and characterize microcapsules incorporating G with a microcapsule-stabilizing bile acid, ursodeoxycholic acid (UDCA). Sodium alginate (SA)-based microcapsules were prepared with either G or G with UDCA and analyzed in terms of morphological, physico-chemical, and electro-chemical characteristics at different pH and temperatures. The microcapsules' effects on viability on muscle cell line (C2C12) and on diabetic rats' blood glucose levels and inflammatory profiles were also examined. Bile acid-based microcapsules maintained their morphology, showed good stability, and compatibility profiles, and the incorporation of UDCA resulted in less G content per microcapsule (p < 0.01) and production of stronger microcapsules that were more resistant to mechanical pressure (p < 0.01). G-UDCA-SA microcapsules enhanced muscle cell viability at higher glucose concentrations compared with control (G-SA and UDCA-SA), and they had strong anti-inflammatory effects on diabetic rats. In addition, the incorporation of UDCA into G microcapsules enhanced the physical characteristics of the microcapsules and optimized G delivery after oral administration.

An Ebola Virus-Like Particle-Based Reporter System Enables Evaluation of Antiviral Drugs In Vivo under Non-Biosafety Level 4 Conditions.

UNLABELLED: Ebola virus (EBOV) is a highly contagious lethal pathogen. As a biosafety level 4 (BSL-4) agent, however, EBOV is restricted to costly BSL-4 laboratories for experimentation, thus significantly impeding the evaluation of EBOV vaccines and drugs. Here, we report an EBOV-like particle (EBOVLP)-based luciferase reporter system that enables the evaluation of anti-EBOV agents in vitro and in vivo outside BSL-4 facilities. Cotransfection of HEK293T cells with four plasmids encoding the proteins VP40, NP, and GP of EBOV and firefly luciferase (Fluc) resulted in the production of Fluc-containing filamentous particles that morphologically resemble authentic EBOV. The reporter EBOVLP was capable of delivering Fluc into various cultured cells in a GP-dependent manner and was recognized by a conformation-dependent anti-EBOV monoclonal antibody (MAb). Significantly, inoculation of mice with the reporter EBOVLP led to the delivery of Fluc protein into target cells and rapid generation of intense bioluminescence signals that could be blocked by the administration of EBOV neutralizing MAbs. This BSL-4-free reporter system should facilitate high-throughput screening for anti-EBOV drugs targeting viral entry and efficacy testing of candidate vaccines. IMPORTANCE: Ebola virus (EBOV) researches have been limited to costly biosafety level 4 (BSL-4) facilities due to the lack of animal models independent of BSL-4 laboratories. In this study, we reveal that a firefly luciferase-bearing EBOV-like particle (EBOVLP) with typical filamentous EBOV morphology is capable of delivering the reporter protein into murine target cells both in vitro and in vivo Moreover, we demonstrate that the reporter delivery can be inhibited both in vitro and in vivo by a known anti-EBOV protective monoclonal antibody, 13C6. Our work provides a BSL-4-free system that can facilitate the in vivo evaluation of anti-EBOV antibodies, drugs, and vaccines. The system may also be useful for mechanistic study of the viral entry process.

The effects of laparoscopic spleen-preserving splenic hilar lymphadenectomy on the surgical outcome of proximal gastric cancer: a propensity score-matched, case-control study.

BACKGROUND: The evidence regarding the long-term results of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPL) has only been rarely reported. The aim of this study was to investigate the feasibility and oncologic efficacy of LSPL for locally advanced proximal gastric cancer. METHODS: From May 2007 to December 2012, we prospectively collected and retrospectively analyzed the data of 548 patients who underwent laparoscopic radical total gastrectomy due to proximal gastric cancer. The patients were grouped according to spleen-preserving splenic hilar lymphadenectomy (200 in the D2 group and 348 in the D2-group). The short- and long-term outcomes were compared between the two groups after propensity score matching. RESULTS: Before matching, TNM stages were significantly different between the D2 and D2-groups. After propensity score matching, the two groups were well balanced in clinicopathologic characteristics. After matching, the time for lymph node dissection was longer in the D2 group, but a greater number of lymph nodes were dissected; the estimated blood loss, time to first flatus and duration of hospital stay were similar in the two groups. Furthermore, no significant differences in morbidity and mortality were found. Before matching, the 3-year overall survival (OS) and disease-free survival (DFS) rates of the D2 group were comparable with those of the D2-group (62.4 vs. 57.7 %, p = 0.076). After matching, the 3-year OS remained comparable, but the D2 group showed significantly longer 3-year DFS (61.6 vs. 53.7 %, p = 0.034). Stratified analysis showed that, in stage III patients, the D2 group had better 3-year DFS. Multivariate Cox regression showed that age (p = 0.003), operation (p = 0.001) and pN stage (p < 0.001) were independent prognostic factors. CONCLUSIONS: LSPL is a safe and feasible procedure, and patients with stage III proximal gastric cancer might obtain higher 3-year DFS rates.