Ab initio molecular dynamics simulations of liquid water under equilibrium ambient conditions, together with a novel energy decomposition analysis, have recently shown that a substantial fraction of water molecules exhibit a significant asymmetry between the strengths of the two donor and/or the two acceptor interactions. We refer to this recently unraveled aspect as the „local asymmetry in the hydrogen bond network”. We discuss how this novel aspect was first revealed, and provide metrics that can be consistently employed on simulated water trajectories to quantify this local heterogeneity in the hydrogen bond network and its dynamics. We then discuss the static aspects of the asymmetry, pertaining to the frozen geometry of liquid water at any given instant of time and the distribution of hydrogen bond strengths therein, and also its dynamic characteristics pertaining to how fast this asymmetry decays and the kinds of molecular motions responsible for this decay. Following this we discuss the spectroscopic manifestations of this asymmetry, from ultrafast X-ray absorption spectra to infrared spectroscopy and down to the much slower terahertz regime. Finally, we discuss the implications of these findings in a broad context and their relation to the current notions about the structure and dynamics of liquid water.We developed a microfluidic droplet on-demand (DoD) generator that enables the production of droplets with a volume solely governed by the geometry of the generator for a range of operating conditions. The prime reason to develop this novel type of DoD generator is that its robustness in operation enables scale out and operation under non-steady conditions, which are both essential features for the further advancement of droplet-based assays. We first detail the working principle of the DoD generator and study the sensitivity of the volume of the generated droplets with respect to the used fluids and control parameters. We next compare the performance of our DoD generator when scaled out to 8 parallel generators to the performance of a conventional DoD generator in which the droplet volume is not geometry-controlled, showing its superior performance. Further scale out to 64 parallel DoD generators shows that all generators produce droplets with a volume between 91% and 105% of the predesigned volume. We conclude the paper by presenting a simple droplet-based assay in which the DoD generator enables sequential supply of reagent droplets to a droplet stored in the device, illustrating its potential to be used in droplet-based assays for biochemical studies under non-steady operation conditions.The cyanobacterial phytochrome Cph2 is a light-dependent diguanylate cyclase of the cyanobacterium Synechocystis 6803. Under blue light, Cph2-dependent increase in the cellular c-di-GMP concentration leads to inhibition of surface motility and enhanced flocculation of cells in liquid culture. However, the targets of second messenger signalling in this cyanobacterium and its mechanism of action remained unclear. Here, we determined the cellular concentrations of cAMP and c-di-GMP in wild-type and Δcph2 cells after exposure to blue and green light. Inactivation of cph2 completely abolished the blue-light dependent increase in c-di-GMP content. Therefore, a microarray analysis with blue-light grown wild-type and Δcph2 mutant cells was used to identify c-di-GMP dependent alterations in transcript accumulation. The increase in the c-di-GMP content alters expression of genes encoding putative cell appendages, minor pilins and components of chemotaxis systems. The mRNA encoding the minor pilins pilA5-pilA6 was negatively affected by high c-di-GMP content under blue light, whereas the minor pilin encoding operon pilA9-slr2019 accumulates under these conditions, suggesting opposing functions of the respective gene sets. Artificial overproduction of c-di-GMP leads to similar changes in minor pilin gene expression and supports previous findings that c-di-GMP is important for flocculation via the function of minor pilins. Mutational and gene expression analysis further suggest that SyCRP2, a CRP-like transcription factor, is involved in regulation of minor pilin and putative chaperone usher pili gene expression.Three metallophyte species, Persicaria capitata, P. puncata (Polygonaceae), Conyza cordata (Asteraceae) from mineral wastes in the Zambian copper-cobalt belt were studied. This study focused on the elemental distribution in the roots, stems and leaves, using a range of techniques micro-PIXE, SEM-EDS synchrotron XFM and XAS. The species differed in their responses to growing on Co-Cu-enriched soils Persicaria puncata is a Co hyperaccumulator (up to 1060 μg g-1 in leaves), while Persicaria capitata and Conyza cordata are Co-excluders. All three species are Cu-accumulators. The highest concentrations of Cu-Co are in the epidermal cells, whereas in Persicaria puncata Co was also enriched in the phloem. The Co coordination chemistry shows that an aqueous Co(ii)-tartrate complex was the predominant component identified in all plants and tissues, along with a minor component of a Co(iii) compound with oxygen donor ligands. For Cu, there was considerable variation in the Cu speciation in the various tissues and across the three species. In contrast to hyperaccumulator plants, excluder and accumulator type plants have received far less attention. This study highlights the different biopathways of transition elements (Cu, Co) in hyper-tolerant plant species showing different responses to metalliferous environments.Introduction The evidence on COVID-19 is being produced at high speed, so it is challenging for decision-makers to keep up. It seems appropriate, then, to put into practice a novel approach able to provide the scientific community and other interested parties with quality evidence that is actionable, and rapidly and efficiently produced. Methods and analysis We designed a protocol for multiple parallel systematic reviews and overviews of systematic reviews in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search for primary studies and systematic reviews that answer different questions related to COVID-19 using both a centralized repository (Epistemonikos database) and a manual search in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We will also search for literature in several other sources. At least two researchers will independently undertake the selection of studies, data extraction, and assessment of the quality of the included studies. We will synthesize data for each question using meta-analysis, when possible, and we will prepare Summary of Findings tables according to the GRADE approach. All the evidence will be organized in an open platform (L·OVE – Living OVerview of Evidence) that will be continuously updated using artificial intelligence and a broad network of experts. Ethics and dissemination No ethics approval is considered necessary. The results of these articles will be widely disseminated via peer-reviewed publications, social networks, and traditional media, and will be sent to relevant international organizations discussing this topic.OBJECTIVE The purpose of this study was to investigate chest computed tomography (CT) findings in children with coronavirus disease-19 (COVID-19) pneumonia in our hospital. METHODS This study included 22 pediatric patients with confirmed COVID-19 from January to March 2020. The chest CT images and clinical data were reviewed. RESULTS The most prevalent presenting symptoms were fever (64%) and cough (59%), and a mildly elevated mean (SD) C-reactive protein (CRP) level of 11.22(11.06) and erythrocyte sedimentation rate of 18.8 (15.17) were detected. The major CT abnormalities observed were mixed ground-glass opacity and consolidation lesions (36%), consolidations (32%), and ground-glass opacities (14%). Peripheral distribution (45%) of lung lesions was predominant. Most of the lesions were multilobar (68%), with an average of three lung segments involved. CONCLUSION Children with COVID-19 had relatively milder symptoms and less severe lung inflammation than adults. Chest CT plays an important role in the management of children with COVID-19 pneumonia.BACKGROUND Cochlear implants (CI) can provide auditory perception to many people with hearing impairment who derive insufficient benefit from hearing aid use. For optimal speech perception with a CI, postoperative auditory training is necessary to adapt the brain to the new sound transmitted by the CI. Currently, this training is usually conducted via face-to-face sessions in rehabilitation centers. With the aging of society, the prevalence of age-related hearing loss and the number of adults with CIs are expected to increase. Therefore, augmenting face-to-face rehabilitation with alternative forms of auditory training may be of great usefulness. OBJECTIVE The purpose of this multidisciplinary study, funded by „Europäische Fonds für regionale Entwicklung EFRE 0800737 GE-1-2-023D”, was to evaluate Train2hear, which is an internet-based teletherapeutic multimodal system. Train2hear enables adult CI users to perform well-structured and therapist-guided hearing rehabilitation sessions on their own. METHODS The stCI users enjoyed their training as assessed by the KIM (mean 19, SD 2.9, maximum 21). In terms of usability (scale 0-100), users rated the Train2hear program as excellent (total mean 88 SD 10.5). Age (P.007) and sex (P .013) had a significant impact on the SUS score with regard to the usability of the program. The therapists (SUS Score mean 93, SD 9.2) gave slightly more positive feedback than CI users (SUS Score mean 85, SD 10.3). CONCLUSIONS Based on this first evaluation, Train2hear was well accepted by CI users and therapists. Computer-based auditory training might be a promising cost-effective option that can provide a highly personalized rehabilitation suited to individual CI user’s characteristics.BACKGROUND Malignancies are the leading cause of disease burden in Australia, comprising 19% of total diseases. Approximately 1 in 4 men and 1 in 6 women die from malignancies by 85 years of age, with patients aged 65 years and older contributing to 58% of diagnoses and 76% of cancer mortality. In the context of malignancy-related disease and age-related degeneration, there is a need for comprehensive assessment of older patients to plan for appropriate management and predict prognosis. The utility of available comprehensive geriatric assessment tools has been limited in routine practice because of their time-consuming nature, despite their informing clearer understanding of patients’ functional status, better clinical decision making, prevention of unpredictable admissions and emergency department overload, and support services planning. Though there are several promising tools available, there is a lack of literature on tools that can comprehensively assess functional status in an expedited fashion. OBJECTId further examination of the tool’s utility and impact in clinical decision making, and the distribution of dependencies in a rural cohort compared with metropolitan patients. ©Mathew George, Alexandra Smith. Originally published in JMIR Cancer (http//cancer.jmir.org), 07.04.2020.BACKGROUND The emergence and advancement of mobile technologies offer a promising opportunity for people with diabetes to improve their self-management. Despite the proliferation of mobile apps, few studies have evaluated the apps that are available to the millions of people with diabetes in China. OBJECTIVE This study aimed to conduct a systematic search of Chinese mobile apps for diabetes self-management and to evaluate their quality, functionality, and features by using validated rating scales. METHODS A systematic search was conducted to identify Chinese apps for diabetes self-management in the four most popular Chinese language mobile app stores. Apps were included if they were designed for diabetes self-management and contained at least one of the following components blood glucose management, dietary and physical activity management, medication taking, and prevention of diabetes-related comorbidities. Apps were excluded if they were unrelated to health, not in Chinese, or the targeted users are health L. Yan, Brian Oldenburg. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 07.04.2020.BACKGROUND With the high prevalence of diabetic retinopathy and its significant visual consequences if untreated, timely identification and management of diabetic retinopathy is essential. Teleophthalmology programs have assisted in screening a large number of individuals at risk for vision loss from diabetic retinopathy. Training nonophthalmological readers to assess remote fundus images for diabetic retinopathy may further improve the efficiency of such programs. OBJECTIVE This study aimed to evaluate the performance, safety implications, and progress of 2 ophthalmology nurses trained to read and assess diabetic retinopathy fundus images within a hospital diabetic retinopathy telescreening program. METHODS In this retrospective interobserver study, 2 ophthalmology nurses followed a specific training program within a hospital diabetic retinopathy telescreening program and were trained to assess diabetic retinopathy images at 2 levels of intervention detection of diabetic retinopathy (level 1) and identificatl 2 readers (readers A and B). This performance was achieved immediately after training and remained stable throughout the study. CONCLUSIONS Notwithstanding the small number of trained readers, this study validates the screening performance of level 1 and level 2 diabetic retinopathy readers within this training program, emphasizing practical experience, and allows the establishment of an ongoing assessment clinic. This highlights the importance of supervised, hands-on experience and may help set parameters to further calibrate the training of diabetic retinopathy readers for safe screening programs. ©Marie Carole Boucher, Michael Trong Duc Nguyen, Jenny Qian. Originally published in JMIR Diabetes (http//diabetes.jmir.org), 07.04.2020.Synaptic positions underlie precise circuit connectivity. Synaptic positions can be established during embryogenesis and sustained during growth. The mechanisms that sustain synaptic specificity during allometric growth are largely unknown. We performed forward genetic screens in C. elegans for regulators of this process and identified mig-17, a conserved ADAMTS metalloprotease. Proteomic mass spectrometry, cell biological and genetic studies demonstrate that MIG-17 is secreted from cells like muscles to regulate basement membrane proteins. In the nematode brain, the basement membrane does not directly contact synapses. Instead, muscle-derived basement membrane coats one side of the glia, while glia contact synapses on their other side. MIG-17 modifies the muscle-derived basement membrane to modulate epidermal-glial crosstalk and sustain glia location and morphology during growth. Glia position in turn sustains the synaptic pattern established during embryogenesis. Our findings uncover a muscle-epidermis-glia signaling axis that sustains synaptic specificity during the organism’s allometric growth. © 2020, Fan et al.Multifunctional proteins are evolutionary puzzles how do proteins evolve to satisfy multiple functional constraints? S100A9 is one such multifunctional protein. It potently amplifies inflammation via Toll-like receptor 4 and is antimicrobial as part of a heterocomplex with S100A8. These two functions are seemingly regulated by proteolysis S100A9 is readily degraded, while S100A8/S100A9 is resistant. We take an evolutionary biochemical approach to show that S100A9 evolved both functions and lost proteolytic resistance from a weakly proinflammatory, proteolytically resistant amniote ancestor. We identify a historical substitution that has pleiotropic effects on S100A9 proinflammatory activity and proteolytic resistance but has little effect on S100A8/S100A9 antimicrobial activity. We thus propose that mammals evolved S100A8/S100A9 antimicrobial and S100A9 proinflammatory activities concomitantly with a proteolytic 'timer’ to selectively regulate S100A9. This highlights how the same mutation can have pleiotropic effects on one functional state of a protein but not another, thus facilitating the evolution of multifunctionality. © 2020, Harman et al.Condensin complexes are essential for mitotic chromosome assembly and segregation during cell divisions, however, little is known about their functions in post-mitotic cells. Here we report a role for the condensin I subunit Cap-G in Drosophila neurons. We show that, despite not requiring condensin for mitotic chromosome compaction, post-mitotic neurons express Cap-G. Knockdown of Cap-G specifically in neurons (from their birth onwards) results in developmental arrest, behavioural defects, and dramatic gene expression changes, including reduced expression of a subset of neuronal genes and aberrant expression of genes that are not normally expressed in the developing brain. Knockdown of Cap-G in mature neurons results in similar phenotypes but to a lesser degree. Furthermore, we see dynamic binding of Cap-G at distinct loci in progenitor cells and differentiated neurons. Therefore, Cap-G is essential for proper gene expression in neurons and plays an important role during the early stages of neuronal development. © 2020, Hassan et al.Mammalian cells typically start the cell-cycle entry program by activating cyclin-dependent protein kinase 4/6 (CDK4/6). CDK4/6 activity is clinically relevant as mutations, deletions, and amplifications that increase CDK4/6 activity contribute to the progression of many cancers. However, when CDK4/6 is activated relative to CDK2 remained incompletely understood. Here we developed a reporter system to simultaneously monitor CDK4/6 and CDK2 activities in single cells and found that CDK4/6 activity increases rapidly before CDK2 activity gradually increases, and that CDK4/6 activity can be active after mitosis or inactive for variable time periods. Markedly, stress signals in G1 can rapidly inactivate CDK4/6 to return cells to quiescence but with reduced probability as cells approach S phase. Together, our study reveals a regulation of G1 length by temporary inactivation of CDK4/6 activity after mitosis, and a progressively increasing persistence in CDK4/6 activity that restricts cells from returning to quiescence as cells approach S phase.Bulk whole genome sequencing (WGS) enables the analysis of tumor evolution but, because of depth limitations, can only identify old mutational events. The discovery of current mutational processes for predicting the tumor’s evolutionary trajectory requires dense sequencing of individual clones or single cells. Such studies, however, are inherently problematic because of the discovery of excessive false positive mutations when sequencing picogram quantities of DNA. Data pooling to increase the confidence in the discovered mutations, moves the discovery back in the past to a common ancestor. Here we report a robust whole genome sequencing and analysis pipeline (DigiPico/MutLX) that virtually eliminates all false positive results while retaining an excellent proportion of true positives. Using our method, we identified, for the first time, a hyper-mutation (kataegis) event in a group of ∼30 cancer cells from a recurrent ovarian carcinoma. This was unidentifiable from the bulk WGS data. Overall, we propose DigiPico/MutLX method as a powerful framework for the identification of clone-specific variants at an unprecedented accuracy. © 2020, KaramiNejadRanjbar et al.Dedifferentiation is a critical response to tissue damage, yet is not well understood, even at a basic phenomenological level. Developing Dictyostelium cells undergo highly efficient dedifferentiation, completed by most cells within 24 hours. We use this rapid response to investigate the control features of dedifferentiation, combining single cell imaging with high temporal resolution transcriptomics. Gene expression during dedifferentiation was predominantly a simple reversal of developmental changes, with expression changes not following this pattern primarily associated with ribosome biogenesis. Mutation of genes induced early in dedifferentiation did not strongly perturb the reversal of development. This apparent robustness may arise from adaptability of cells the relative temporal ordering of cell and molecular events was not absolute, suggesting cell programmes reach the same end using different mechanisms. In addition, although cells start from different fates, they rapidly converged on a single expression trajectory. These regulatory features may contribute to dedifferentiation responses during regeneration. © 2020, Nichols et al.Particulate matter (PM) air pollution causes cardiopulmonary mortality via macrophage-driven lung inflammation; however, the mechanisms are incompletely understood. RNA-sequencing demonstrated Acod1 (Aconitate decarboxylase 1) as one of the top genes induced by PM in macrophages. Acod1 encodes a mitochondrial enzyme that produces itaconate, which was shown to exert anti-inflammatory effects via NRF2 after LPS. Here, we demonstrate that PM induces Acod1 and itaconate, which reduced mitochondrial respiration via complex II inhibition. Using Acod1-/- mice, we found that Acod1/endogenous itaconate does not affect PM-induced inflammation or NRF2 activation in macrophages in vitro or in vivo. In contrast, exogenous cell permeable itaconate, 4-octyl itaconate (OI) attenuated PM-induced inflammation in macrophages. OI was sufficient to activate NRF2 in macrophages; however, NRF2 was not required for the anti-inflammatory effects of OI. We conclude that the effects of itaconate production on inflammation are stimulus-dependent, and that there are important differences between endogenous and exogenously-applied itaconate. © 2020, Sun et al.Goal-directed attention is usually studied by providing individuals with explicit instructions on what they should attend to. But in daily life, we often use past experiences to guide our attentional states. Given the importance of memory for predicting upcoming events, we hypothesized that memory-guided attention is supported by neural preparation for anticipated attentional states. We examined preparatory coding in the human hippocampus and mPFC, two regions that are important for memory-guided behaviors, in two tasks one where attention was guided by memory and another in which attention was explicitly instructed. Hippocampus and mPFC exhibited higher activity for memory-guided vs. explicitly instructed attention. Furthermore, representations in both regions contained information about upcoming attentional states. In the hippocampus, this preparation was stronger for memory-guided attention, and occurred alongside stronger coupling with visual cortex during attentional guidance. These results highlight the mechanisms by which memories are used to prepare for upcoming attentional goals. © 2020, Günseli & Aly.Wiring a complex brain requires many neurons with intricate cell specificity, generated by a limited number of neural stem cells. Drosophila central brain lineages are a predetermined series of neurons, born in a specific order. To understand how lineage identity translates to neuron morphology, we mapped 18 Drosophila central brain lineages. While we found large aggregate differences between lineages, we also discovered shared patterns of morphological diversification. Lineage identity plus Notch-mediated sister fate govern primary neuron trajectories, whereas temporal fate diversifies terminal elaborations. Further, morphological neuron types may arise repeatedly, interspersed with other types. Despite the complexity, related lineages produce similar neuron types in comparable temporal patterns. Different stem cells even yield two identical series of dopaminergic neuron types, but with unrelated sister neurons. Together, these phenomena suggest that straightforward rules drive incredible neuronal complexity, and that large changes in morphology can result from relatively simple fating mechanisms. © 2020, Lee et al.All of the known porcine sapeloviruses (PSVs) currently belong to a single genotype in the genus Sapelovirus (family Picornaviridae). Here, the complete genome of a second, possibly recombinant, genotype of PSV strain SZ1M-F/PSV/HUN2013 (MN807752) from a faecal sample of a paraplegic pig in Hungary was characterized using viral metagenomics and RT-PCR. This sapelovirus strain showed only 64 % nucleotide identity in the VP1 region to its closest PSV-1 relative. Complete VP1 sequence-based epidemiological investigations of PSVs circulating in Hungary showed the presence of diverse strains found in high prevalence in enteric and respiratory samples collected from both asymptomatic and paraplegic pigs from 12 swine farms. Virus isolation attempts using PK-15 cell cultures were successful in 3/8 cases for the classic but not the novel PSV genotype. Sequence comparisons of faeces and isolate strains derived VP1 showed that cultured PSV strains not always represent the dominant PSVs found in vivo.A theoretical model is built in this study for analyzing and predicting the deformation of a bending-type soft pneumatic actuator used for bionic robotic fish. The actuator is composed of two symmetrically distributed silicone rubber blocks (Ecoflex0030 from Smooth-on Co., Ltd.). Between the two rubber blocks, an ABS plate is fixed to work as a neutral layer. When one side of the actuator is inflated, it consequently bends toward the uninflated side. The deformation of the actuator on the inflated side and the uninflated side, respectively, is analyzed based on principles of elasticity mechanics. The deformation on the inflated side is simplified to planar type and is decomposed into two mutually perpendicular directions to analyze the stress state. A two-step deforming process is proposed to study the stress state on the uninflated side. The two components are combined to determine the relationship between the bending angle of the actuator and the actuating pressure. The proposed model is compared with a finite element analysis model in which the same constraint, load, and materials are used. An experiment under the same conditions was implemented to validate the model. The experiment demonstrates that the accuracy of the theoretical model is adequate to indicate the response of the soft pneumatic actuator to the actuating pressure. A bionic fishtail system based on the soft pneumatic actuator was also established to verify the applicability of the actuator to bionic robotic fish.Background MRI performed at 3.0 T offers greater signal-to-noise ratio and better spatial resolution than does MRI performed at 1.5 T; however, for fetal MRI, there are concerns about the potential for greater radiofrequency energy administered to the fetus at 3.0-T MRI. Purpose To compare the specific absorption rate (SAR) and specific energy dose (SED) of fetal MRI at 1.5 and 3.0 T. Materials and Methods In this retrospective study, all fetal MRI examinations performed with 1.5- and 3.0-T scanners at one institution between July 2012 and October 2016 were evaluated. Two-dimensional (2D) and three-dimensional (3D) steady-state free precession (SSFP), single-shot fast spin-echo, 2D and 3D T1-weighted spoiled gradient-echo (SPGR), and echo-planar imaging sequences were performed. SAR, SED, accumulated SED, and acquisition time were retrieved from the Digital Imaging and Communications in Medicine header. Data are presented as mean ± standard deviation. Two one-sided tests with equivalence bounds of 0.5 (Cohen ed to the patient as low as possible. © RSNA, 2020.Background Although artificial intelligence (AI) shows promise across many aspects of radiology, the use of AI to create differential diagnoses for rare and common diseases at brain MRI has not been demonstrated. Purpose To evaluate an AI system for generation of differential diagnoses at brain MRI compared with radiologists. Materials and Methods This retrospective study tested performance of an AI system for probabilistic diagnosis in patients with 19 common and rare diagnoses at brain MRI acquired between January 2008 and January 2018. The AI system combines data-driven and domain-expertise methodologies, including deep learning and Bayesian networks. First, lesions were detected by using deep learning. Then, 18 quantitative imaging features were extracted by using atlas-based coregistration and segmentation. Third, these image features were combined with five clinical features by using Bayesian inference to develop probability-ranked differential diagnoses. Quantitative feature extraction algorithms and c system for brain MRI approached overall top one, top two, and top three differential diagnoses accuracy of neuroradiologists and exceeded that of less-specialized radiologists. © RSNA, 2020 See also the editorial by Zaharchuk in this issue.Background Current measurements of multiple myeloma disease burden are suboptimal. Daratumumab is a monoclonal antibody that targets CD38, an antigen expressed on nearly all myeloma cells. Purpose To demonstrate preclinical and first-in-human application of an antibody composed of the native daratumumab labeled with the positron-emitting radionuclide zirconium 89 (89Zr) through the chelator deferoxamine (DFO), or 89Zr-DFO-daratumumab, for immunologic PET imaging of multiple myeloma. Materials and Methods 89Zr-DFO-daratumumab was synthesized by conjugating 89Zr to daratumumab with DFO. A murine xenograft model using CD38-positive OPM2 multiple myeloma cells was used to evaluate CD38-specificity of 89Zr-DFO-daratumumab. Following successful preclinical imaging, a prospective phase I study of 10 patients with multiple myeloma was performed. Study participants received 74 MBq (2 mCi) of intravenous 89Zr-DFO-daratumumab. Each participant underwent four PET/CT scans over the next 8 days, as well as blood chemistry and whole-body counts, to determine safety, tracer biodistribution, pharmacokinetics, and radiation dosimetry. Because 89Zr has a half-life of 78 hours, only a single administration of tracer was needed to obtain all four PET/CT scans. Results 89Zr-DFO-daratumumab was synthesized with radiochemical purity greater than 99%. In the murine model, substantial bone marrow uptake was seen in OPM2 mice but not in healthy mice, consistent with CD38-targeted imaging of OPM2 multiple myeloma cells. In humans, 89Zr-DFO-daratumumab was safe and demonstrated acceptable dosimetry. 89Zr-DFO-daratumumab uptake was visualized at PET in sites of osseous myeloma. Conclusion These data demonstrate successful CD38-targeted immunologic PET imaging of multiple myeloma in a murine model and in humans. © RSNA, 2020 .Background Identification of markers to aid in understanding the growth kinetics of Von Hippel-Lindau (VHL)-associated clear cell renal cell carcinoma (ccRCC) has the potential to allow individualization of patient care, thereby helping prevent unnecessary screening and optimizing intervention. Purpose To determine whether the degree of restricted diffusion at baseline MRI holds predictive potential for the growth rate of VHL-associated ccRCC. Materials and Methods Patients with VHL disease who underwent surgical resection of tumors between November 2014 and October 2017 were analyzed retrospectively in this HIPAA-compliant study. The change in ccRCC volume between two time points and apparent diffusion coefficient (ADC) at baseline was calculated by using segmentations by two readers at nephrographic-phase CT and diffusion-weighted MRI, respectively. Intraclass correlation coefficient was used to assess agreement between readers. Repeated-measures correlation was used to investigate relationships between ADCon-weighted MRI may be useful to identify clear cell renal cell carcinomas with higher growth rates. © RSNA, 2020.Background Performance metrics with digital breast tomosynthesis (DBT) are based on early experiences. There is limited research on whether the benefits of DBT are sustained. Purpose To determine whether improved screening performance metrics with DBT are sustained over time at the population level and after the first screening round at the individual level. Materials and Methods A retrospective review was conducted of screening mammograms that had been obtained before DBT implementation (March 2008 to February 2011, two-dimensional digital mammography [DM] group) and for 5 years after implementation (January 2013 to December 2017, DBT1-DBT5 groups, respectively). Patients who underwent DBT were also categorized according to the number of previous DBT examinations they had undergone. Performance metrics were compared between DM and DBT groups and between patients with no previous DBT examinations and those with at least one prior DBT examination by using multivariable logistic regression models. Results The D groups (P less then .001 to P = .004). The increase in specificity was also sustained after the first examination (P less then .001 to P = .01). Conclusion The benefits of reduced false-positive examinations and higher specificity with screening tomosynthesis were sustained after the first screening round at the individual level. © RSNA, 2020 See also the editorial by Taourel in this issue.With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first three months of 2020, the COVID-19 pandemic has emerged as an unprecedented healthcare crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, healthcare delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and healthcare workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. While mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography (CXR) and computed tomography (CT) are key tools for pulmonary disease diagnosis and management, but t9.Tigecycline is a broad-spectrum antibiotic that is indicated in the treatment of complicated intra-abdominal infections and complicated skin and skin and soft-tissue infections. We report the case of a 53-year old kidney transplant patient with a severe Mycobacterium abscess who developed life-threatening coagulopathy after initiation of tigecycline therapy. Further analysis revealed a severe hypofibrinogenemia. A few case reports previously described an association between tigecycline and prolongation of clotting time. Our case confirms an uncommon yet possibly life-threatening side-effect of tigecycline. Medical practitioners should be aware of this potential coagulopathy and we recommend routine monitoring of coagulation parameters in patients receiving tigecycline.Objective The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common. Individuals with PTSD/AUD commonly drink to cope with PTSD symptoms, which maintains PTSD/AUD, and may result in increased craving for alcohol. Negative affect is implicated in negative reinforcement models of craving. Further, Emotional Processing Theory posits that posttraumatic cognitions lead to the experience of negative affect, which may result in increased craving in PTSD/AUD. The current study aims to advance the understanding of craving in PTSD/AUD by evaluating if specific posttraumatic cognitions (e.g., cognitions about the self, world, and self-blame) are associated with increased negative affect, and whether higher negative affect is associated with heightened craving. Methods Three separate simple mediation models were utilized to test if negative affect mediated the relationship between each specific posttraumatic cognition type and craving among 136 treatment-seeking veterans with PTSD/AUD. Results We found that negative affect mediated the association between all posttraumatic cognition types and craving. Specifically, viewing oneself as being unable to handle PTSD-related distress, viewing the world as very dangerous, and blaming oneself for one’s role in a traumatic event were all associated with increased negative affect, which was related to higher craving. Conclusions Given that posttraumatic cognitions improve via trauma-focused treatment for PTSD, future work should evaluate whether improvements in posttraumatic cognitions via trauma-focused treatment lead to decreased negative affect and craving in PTSD/AUD.Poor coordination between different healthcare services means that the proper follow-up of patients cannot be guaranteed, thus increasing the risk of relapse in cases of attempted suicide. This study describes the sociodemographic variables related to suicidal behaviour in a Spanish sample and analyses how the use of a continued nursing care protocol influences the follow-up of patients who have shown suicidal behaviour. A cohort of 213 patient was identified from the emergency department medical records because of suicide attempters during 2011; 51.6% were included in the intervention group (n = 110) and 48.4% (n = 103) in the control group. We used a specific continuity of care chain protocol with the patients in the intervention group. More than half of all the initial suicide attempts were made by women; 80.3% had a previous history of a mental disorder and 65.7% of the attempts were made by ingesting medications. Significantly more patients in the intervention group attended their first follow-up visit. This study highlights the need to implement protocols that favour the continuity of mental health care processes-especially those designed to treat individuals expressing suicidal behaviour-with the aim of reducing the risk of suicide in them by intensifying their monitoring.Objective Citrullus vulgaris seeds are the most concealed oil seeds consist of vital therapeutic potential. Apart from nutritional and therapeutic indices, these seeds contain numerous anti-nutritional components.Method Hence, solid-state fermentation was used as an alternative biotechnological contrivance to enhance the nutritional and functional properties of seeds. Fungal strain Aspergillus awamori was used for solid-state fermentation and uncoated watermelon seeds were used as a substrate for 144h. The range of bulk density was obtained from 0.39 to 0.72 g/cm3, however, fermentation significantly decreased the bulk density of the seed flours. Based upon soluble nitrogen content (79.81%) and functional properties, fermented seed samples of 120h was selected for FTIR analysis and in-vitro mineral bioavailability through Caco-2 cells.Results FTIR spectrum confirmed the presence of amide groups (1200-1100 cm-1) of the protein.Conclusion Fermented seeds also unveiled significantly (p less then 0.05) higher iron (61.24%), zinc (62.36%), and calcium (61.89%) bioavailability and this significant increase in bioavailability confirmed significantly (p less then 0.05) higher cellular mineral uptake.In this secondary analysis of 138 community-dwelling women caregivers of persons with dementia, we examined whether caregiver resourcefulness mediated the effects of both the frequency of and reactions to their care recipients’ memory-related, depressive, and disruptive symptoms of dementia on caregiver depressive symptoms. Caregiver resourcefulness mediated the effects of care recipient depressive symptoms on caregiver depressive symptoms, and the effects of caregiver actions to depressive and disruptive symptoms on caregiver depressive symptoms. The findings suggest the potential benefit of teaching resourcefulness skills to reduce depressive symptoms of caregivers whose care recipients frequently exhibited depressive or disruptive symptoms associated with dementia.Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is a potentially underdiagnosed inherited dyslipidemia associated with greatly increased risk of coronary and peripheral vascular disease. The mixed hyperlipidemia observed in this disorder usually responds well to appropriate medical therapy and lifestyle modification. Although there are characteristic clinical features such as palmar and tuberous xanthomata, associated with dysbetalipoproteinemia, they are not always present, and their absence cannot be used to exclude the disorder. The routine lipid profile cannot distinguish dysbetalipoproteinemia from other causes of mixed hyperlipidemia and so additional investigations are required for confident diagnosis or exclusion. A range of investigations that have been proposed as potential diagnostic tests are discussed in this review, but the definitive biochemical test for dysbetalipoproteinemia is widely considered to be beta quantification. Beta quantification can determine the presence of „β-VLautosomal dominant mutations in APOE that will only be detected if the gene is fully sequenced. Wider implementation of diagnostic pathways utilizing apo B could lead to more rational use of specialist investigations and more consistent detection of patients with dysbetalipoproteinemia. Without the application of a consistent evidence-based approach to identifying dysbetalipoproteinemia, many cases are likely to remain undiagnosed.Objective A significant portion of colorectal cancer patients lose weight preoperatively. Here we examine the influence of pre-operative significant weight loss on venous thromboembolism (VTE) risk and determine whether pre-operative BMI and albumin could influence VTE outcomes in patients who have lost significant weight prior to surgery.Methods We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and identified 103,455 colorectal cancer patients undergoing major surgery from 2008 to 2012. Patients were assigned to one of two groups based on whether they lost significant weight preoperatively or not. Simple and stepwise multiple logistic regressions were used to evaluate the association between pre-operative unintended weight loss and 30-days postoperative outcomes. The association between weight loss and postoperative thrombosis was further assessed across several strata.Results The overall prevalence of pre-operative significant weight loss was 6.8%. Significant weight loss prior to surgery was significantly and independently associated with a higher risk of VTE (adjusted OR 1.23, 95% CI 1.06-1.44), mortality (adjusted OR 1.55, 95% CI 1.35-1.78), composite morbidity (adjusted OR 1.52, 95% CI 1.42-1.62), bleeding (adjusted OR 1.78, 95% CI 1.67-1.91) and return to operation room (adjusted OR 1.29, 95% CI 1.16-1.42). The effect of pre-operative significant weight loss on thromboembolic outcome was evident across patients with a BMI 40kg/m2.Conclusions Significant weight loss and BMI both need to be measured preoperatively to stratify patients who are at a higher risk of VTE.We aimed to assess the occurrence of bovine viruses (bovine leukemia virus-BLV and bovine adenovirus-BAdV) at workplaces in traditional dairies and to evaluate the potential role of airborne and surface contamination in spreading of these viruses derived from raw milk. The total amount of 122 samples-including 37 air (bioaerosol), 40 surface, and 45 milk samples-were checked for the presence of BLV and BAdV genomes using RT-qPCR/qPCR method. The study showed that the viruses were present in 7 air (among them 71.4% were BLV-positive and 28.6% were BAdV-positive), 14 surface (among them 85.7% were BLV-positive and 14.3% were BAdV-positive), and 34 milk (all were BLV-positive only) samples. Statistical analysis revealed that both the air and surfaces in studied occupational environment were more frequently contaminated with BLV than with BAdV (Chi-square test p = 0.002, Fisher’s Exact test p = 0.002). Kruskal-Wallis tests showed significant differences in BLV genome concentrations in the air (p = 0.045) as well ction zones, should be required. As the raw milk may be a source of bovine viruses, the development of strategies for both the control and eradication of BLV and BAdV among cattle seems to be also urgently needed.Background Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurobiological disorders in childhood. Maternal resilience has been linked to treatment outcome in child ADHD. However, not much is known about factors that may facilitate maternal resilience.Aim The aim of this study was to explore factors potentially facilitating resilience in mothers to children with ADHD.Method The current study was part of a naturalistic observational study. 64 mothers to children diagnosed with ADHD completed a set of questionnaires and a short protocol including demographic and psychosocial items. Correlation matrix were estimated for each of the scores to establish the relationship between them.Results We found significant negative correlations between maternal self-reported attachment style and self-reported resilience and between self-reported ADHD-symptoms and resilience-score.Conclusion The findings indicate that selected factors in maternal functioning may contribute to development of resilience, which may in turn be a factor of importance in parenting.Objective To synthesise qualitative research that explored caregivers’ experiences of caring for family diagnosed with schizophrenia.Methods Electronic databases including PsycINFO, PubMed, CINAHL and Scopus were searched to identify relevant journal articles published from 2000 to March 2019. Quality was assessed and thematic synthesis of the qualitative research evidence undertaken. Papers were screened and independently appraised by two reviewers using The Critical Appraisal Skills Programme (CASP) for Qualitative Studies Checklist. The review was guided by Thomas and Harden’s framework for thematic synthesis of qualitative research evidence.Results The breadth of information across the 43 papers was noteworthy. Review of the findings noted that almost all of what was discussed fell into three broad themes the 'feelings’ of the caregiver towards their role, the patient and others, including the health system; the 'impacts’ of the diagnosis and their caregiving role on the caregiver; and the 'needs’ of the caregiver to improve the patient’s quality of life and thereby the caregiver’s quality of life. Within needs also came recommendations for future changes.Conclusion Studies have shown that the caregiving process is a complex one, with both negative and positive emotional reactions, societal barriers, such as stigma and isolation, and unmet needs, such as timely, relevant and helpful information. Meeting the needs identified by caregivers has the capacity to address the impacts of the illness and caregiving and thereby reduce the negative feelings associated with the caregiver role.Context Satureja khuzistanica Jamzad. (Lamiaceae), is known for its antifungal and antioxidant compounds, especially rosmarinic acid (RA).Objective The study examines the effect of elicitors on RA production and phytochemical properties of S. khuzistanica.Materials and methods In vitro plants were treated with methyl jasmonate (MeJA) and multi-walled carbon nanotubes (MWCNTs). In vivo plants were treated with MWCNTs and salicylic acid (SA). RA was measured by HPLC. Catalase (CAT), guaiacol peroxidase (POD) and ascorbate peroxidase (APX) were quantified. DPPH and β-carotene were assayed in in vivo extracts. The antifungal effects of extracts were evaluated against Fusarium solani K (FsK).Results The highest RA contents of in vitro plants were 50 mg/L MeJA (140.99 mg/g DW) and 250 mg/L MWCNTs (140.49 mg/g DW). The highest in vivo were 24 h MWCNTs (7.13 mg/g DW) and 72 h SA (9.12 mg/g DW). The maximum POD and APX activities were at 100 mg/L MeJA (5 and 4 mg protein, respectively). CAT had the highest activities at 50 mg/L MeJA (2 mg protein). DPPH and β-carotene showed 50% and 80% inhibition, respectively. The FsK aggregation was the lowest for in vitro extract in number of conidia [1.82 × 1010], fresh weight (6.51 g) and dry weight (0.21 g) that proved RA inhibitory effects. The callus reduces FsK growth diameter to 2.75 on the 5th day.Discussion and conclusions Application of MeJA, SA, and MWCNTSs could increase RA in S. khuzistanica and highlighted potential characteristics in pharmaceutical and antifungal effects.The regenerative thermal oxidizer (RTO) is widely used in the treatment of volatile organic compounds (VOCs). The RTO with three packed beds has a backflushing process, which makes its operation quite different from common regenerative combustion devices with two beds. However, the published research regarding this kind of RTO was far from sufficient. Thus, models based on an industrial RTO with three beds were developed. Temperature distributions for the RTO were simulated based on the standard k-ε model, heat balance model, DO model, and finite chemical-rate/eddy-dissipation model after model validation. Four operating parameters were selected, and these parameters have a significant impact on key factors, such as the oxidation chamber temperature (OCT), outlet temperature, and thermal efficiency. Multi-factor analysis was performed by orthogonal experiment and regression analysis of the key factors, revealing that different parameters imposed various impacts on the key factors. A linear relationship between the OCT and RTO outlet temperature was identified, yielding a useful formula for engineering applications. Implications StatementA regenerative thermal oxidizer (RTO) used in volatile organic compounds (VOCs) treatment was studied between engineering and simulation. The simulation results showed a few error compared to the engineering ones. Single parameter simulations, orthogonal experiments and regression analysis were applied to study key factors such as oxidation chamber temperature, outlet temperature, and thermal efficiency. The influence and regularity of the four main operating parameters on the key factors were quite different. The best condition for this RTO was got. The linear formula of the oxidation chamber temperature and the outlet temperature are obtained, respectively.Purpose To investigate the efficacy of once-daily topical treatment of ocular and cutaneous rosacea with ivermectin 1% cream (Soolantra®, Galderma).Methods Ten patients with rosacea were evaluated in a retrospective monocentric pilot study. Subjective symptoms (measured with the Ocular Surface Disease Index), skin findings, and ocular changes (blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, tear breakup time (TBUT), and fluorescein staining of the cornea) were evaluated. The follow-up was 8 months (range 5-12 months).Results The OSDI score decreased in the 8th week of treatment (38.5 ± 21.7, P = .004). After 16 weeks, blepharitis (P = .004), and conjunctival redness (P = .008) had strongly improved, and grade 1 was seen in all patients until the end of follow-up. Fluorescein staining of the cornea (P = .001) and TBUT (P = .016) showed significant improvement until the last follow-up visit. No side effects were observed. Conclusion Topical ivermectin cream 1% given daily is an effective and safe therapy against rosacea.