The oncomicropeptide APPLE promotes hematopoietic malignancy by enhancing translation initiation.

Initiation is the rate-limiting step in translation, and its dysregulation is vital for carcinogenesis, including hematopoietic malignancy. Thus, discovery of novel translation initiation regulators may provide promising therapeutic targets. Here, combining Ribo-seq, mass spectrometry, and RNA-seq datasets, we discovered an oncomicropeptide, APPLE (a peptide located in ER), encoded by a non-coding RNA transcript in acute myeloid leukemia (AML). APPLE is overexpressed in various subtypes of AML and confers a poor prognosis. The micropeptide is enriched in ribosomes and regulates the initiation step to enhance translation and to maintain high rates of oncoprotein synthesis. Mechanically, APPLE promotes PABPC1-eIF4G interaction and facilitates mRNA circularization and eIF4F initiation complex assembly to support a specific pro-cancer translation program. Targeting APPLE exhibited broad anti-cancer effects in vitro and in vivo. This study not only reports a previously unknown function of micropeptides but also provides new opportunities for targeting the translation machinery in cancer cells.

SDPRX: A statistical method for cross-population prediction of complex traits.

Polygenic risk score (PRS) has demonstrated its great utility in biomedical research through identifying high-risk individuals for different diseases from their genotypes. However, the broader application of PRS to the general population is hindered by the limited transferability of PRS developed in Europeans to non-European populations. To improve PRS prediction accuracy in non-European populations, we develop a statistical method called SDPRX that can effectively integrate genome wide association study summary statistics from different populations. SDPRX automatically adjusts for linkage disequilibrium differences between populations and characterizes the joint distribution of the effect sizes of a variant in two populations to be both null, population specific, or shared with correlation. Through simulations and applications to real traits, we show that SDPRX improves the prediction performance over existing methods in non-European populations.

Follicular lymphoma evolves with a surmountable dependency on acquired glycosylation motifs in the B-cell receptor.

ABSTRACT: An early event in the genesis of follicular lymphoma (FL) is the acquisition of new glycosylation motifs in the B-cell receptor (BCR) due to gene rearrangement and/or somatic hypermutation. These N-linked glycosylation motifs (N-motifs) contain mannose-terminated glycans and can interact with lectins in the tumor microenvironment, activating the tumor BCR pathway. N-motifs are stable during FL evolution, suggesting that FL tumor cells are dependent on them for their survival. Here, we investigated the dynamics and potential impact of N-motif prevalence in FL at the single-cell level across distinct tumor sites and over time in 17 patients. Although most patients had acquired at least 1 N-motif as an early event, we also found (1) cases without N-motifs in the heavy or light chains at any tumor site or time point and (2) cases with discordant N-motif patterns across different tumor sites. Inferring phylogenetic trees of the patients with discordant patterns, we observed that both N-motif-positive and N-motif-negative tumor subclones could be selected and expanded during tumor evolution. Comparing N-motif-positive with N-motif-negative tumor cells within a patient revealed higher expression of genes involved in the BCR pathway and inflammatory response, whereas tumor cells without N-motifs had higher activity of pathways involved in energy metabolism. In conclusion, although acquired N-motifs likely support FL pathogenesis through antigen-independent BCR signaling in most patients with FL, N-motif-negative tumor cells can also be selected and expanded and may depend more heavily on altered metabolism for competitive survival.

METTL3 protects METTL14 from STUB1-mediated degradation to maintain m6 A homeostasis.

N6 -Methyladenosine (m6 A) is an important RNA modification catalyzed by methyltransferase-like 3 (METTL3) and METTL14. m6 A homeostasis mediated by the methyltransferase (MTase) complex plays key roles in various biological processes. However, the mechanism underlying METTL14 protein stability and its role in m6 A homeostasis remain elusive. Here, we show that METTL14 stability is regulated by the competitive interaction of METTL3 with the E3 ligase STUB1. STUB1 directly interacts with METTL14 to mediate its ubiquitination at lysine residues K148, K156, and K162 for subsequent degradation, resulting in a significant decrease in total m6 A levels. The amino acid regions 450-454 and 464-480 of METTL3 are essential to promote METTL14 stabilization. Changes in STUB1 expression affect METTL14 protein levels, m6 A modification and tumorigenesis. Collectively, our findings uncover an ubiquitination mechanism controlling METTL14 protein levels to fine-tune m6 A homeostasis. Finally, we present evidence that modulating STUB1 expression to degrade METTL14 could represent a promising therapeutic strategy against cancer.

Farnesoid X Receptor Protects Murine Lung against IL-6-promoted Ferroptosis Induced by Polyriboinosinic-Polyribocytidylic Acid.

Various infections trigger a storm of proinflammatory cytokines in which IL-6 acts as a major contributor and leads to diffuse alveolar damage in patients. However, the metabolic regulatory mechanisms of IL-6 in lung injury remain unclear. Polyriboinosinic-polyribocytidylic acid [poly(I:C)] activates pattern recognition receptors involved in viral sensing and is widely used in alternative animal models of RNA virus-infected lung injury. In this study, intratracheal instillation of poly(I:C) with or without an IL-6-neutralizing antibody model was combined with metabonomics, transcriptomics, and so forth to explore the underlying molecular mechanisms of IL-6-exacerbated lung injury. We found that poly(I:C) increased the IL-6 concentration, and the upregulated IL-6 further induced lung ferroptosis, especially in alveolar epithelial type II cells. Meanwhile, lung regeneration was impaired. Mechanistically, metabolomic analysis showed that poly(I:C) significantly decreased glycolytic metabolites and increased bile acid intermediate metabolites that inhibited the bile acid nuclear receptor farnesoid X receptor (FXR), which could be reversed by IL-6-neutralizing antibody. In the ferroptosis microenvironment, IL-6 receptor monoclonal antibody tocilizumab increased FXR expression and subsequently increased the Yes-associated protein (YAP) concentration by enhancing PKM2 in A549 cells. FXR agonist GW4064 and liquiritin, a potential natural herbal ingredient as an FXR regulator, significantly attenuated lung tissue inflammation and ferroptosis while promoting pulmonary regeneration. Together, the findings of the present study provide the evidence that IL-6 promotes ferroptosis and impairs regeneration of alveolar epithelial type II cells during poly(I:C)-induced murine lung injury by regulating the FXR-PKM2-YAP axis. Targeting FXR represents a promising therapeutic strategy for IL-6-associated inflammatory lung injury.

Novel protein ligase based on dual split intein.

Inteins are unique single-turnover enzymes that can excise themselves from the precursor protein without the aid of any external cofactors or energy. In most cases, inteins are covalently linked with the extein sequences and protein splicing happens spontaneously. In this study, a novel protein ligation system was developed based on two atypical split inteins without cross reaction, in which the large segments of one S1 and one S11 split intein fusion protein acted as a protein ligase, the small segments (only several amino acids long) was fused to the N-extein and C-extein, respectively. The splicing activity was demonstrated in E. coli and in vitro with different extein sequences, which showed ∼15% splicing efficiency in vitro. The protein trans-splicing in vitro was further optimized, and possible reaction explanations were explored. As a proof of concept, we expect this approach to expand the scope of trans-splicing-based protein engineering and provide new clues for intein based protein ligase.

Realization of High-Performance Self-Powered Polarized Photodetection with Large Temperature Window in a 2D Polar Perovskite.

Polarization photodetection taking advantage of the anisotropy of 2D materials shines brilliantly in optoelectronic fields owing to differentiating optical information. However, the previously reported polarization detections are mostly dependent on external power sources, which is not conducive to device integration and energy conservation. Herein, a 2D polar perovskite (CBA)2CsPb2Br7 (CCPB, CBA = 4-chlorobenzyllamine) has been successfully synthesized, which shows anticipated bulk photovoltaic effect (BPVE) with an open-circuited photovoltage up to ≈0.2 V. Devices based on CCPB monomorph fulfill a fascinating self-powered polarized photodetection with a large polarization ratio of 2.7 at room temperature. Moreover, CCPB features a high phase-transition temperature (≈475 K) which prompts such self-powered polarized photodetection in a large temperature window of device operation, since BPVE generated by spontaneous polarization can only exist in the polar structure prior to the phase transition. Further computational investigation reveals the introduction of CBA+ with a large dipole moment contributes to quite large polarization (17.5 µC cm-2) and further super high phase transition temperature of CCPB. This study will promote the application of 2D perovskite materials for self-powered polarized photodetection in high-temperature conditions.

Lymphocyte-to-Monocyte Ratio Predicts Survival for Intraductal Papillary Mucinous Neoplasm with Associated Invasive Carcinoma of the Pancreas: Results from a High-volume Center.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is an important precursor lesion of pancreatic cancer. Systemic inflammatory parameters are widely used in the prognosis prediction of cancer; however, their prognostic implications in IPMN with associated invasive carcinoma (IPMN-INV) are unclear. This study aims to explore the prognostic value of systemic inflammatory parameters in patients with IPMN-INV. METHODS: From 2015 to 2021, patients with pathologically confirmed IPMN who underwent surgical resection at Peking Union Medical College Hospital were enrolled. The clinical, radiological and pathological data of the enrolled patients were collected and analyzed. Preoperative systemic inflammatory parameters were calculated as previously reported. RESULTS: Eighty-six patients with IPMN-INV met the inclusion criteria. The lymphocyte-to-monocyte ratio (LMR) was the only systemic inflammatory parameter independently associated with the cancer-specific survival (CSS). An LMR higher than 3.5 was significantly associated with a favorable CSS in univariate (hazard ratio (HR) 0.305, P = 0.003) and multivariate analyses (HR 0.221, P = 0.001). Other independently prognostic factors included the presence of clinical symptoms, cyst size, N stage and tumor differentiation. Additionally, a model including LMR was established for the prognosis prediction of IPMN-INV and had a C-index of 0.809. CONCLUSIONS: Preoperative LMR could serve as a feasible prognostic biomarker for IPMN-INV. A decreased LMR (cutoff value of 3.5) was an independent predictor of poor survival for IPMN-INV.

Binary All-polymer Solar Cells with a Perhalogenated-Thiophene-Based Solid Additive Surpass 18 % Efficiency.

Morphological control of all-polymer blends is quintessential yet challenging in fabricating high-performance organic solar cells. Recently, solid additives (SAs) have been approved to be capable in tuning the morphology of polymer: small-molecule blends improving the performance and stability of devices. Herein, three perhalogenated thiophenes, which are 3,4-dibromo-2,5-diiodothiophene (SA-T1), 2,5-dibromo-3,4-diiodothiophene (SA-T2), and 2,3-dibromo-4,5-diiodothiophene (SA-T3), were adopted as SAs to optimize the performance of all-polymer organic solar cells (APSCs). For the blend of PM6 and PY-IT, benefitting from the intermolecular interactions between perhalogenated thiophenes and polymers, the molecular packing properties could be finely regulated after introducing these SAs. In situ UV/Vis measurement revealed that these SAs could assist morphological character evolution in the all-polymer blend, leading to their optimal morphologies. Compared to the as-cast device of PM6 : PY-IT, all SA-treated binary devices displayed enhanced power conversion efficiencies of 17.4-18.3 % with obviously elevated short-circuit current densities and fill factors. To our knowledge, the PCE of 18.3 % for SA-T1-treated binary ranks the highest among all binary APSCs to date. Meanwhile, the universality of SA-T1 in other all-polymer blends is demonstrated with unanimously improved device performance. This work provide a new pathway in realizing high-performance APSCs.

Proposal for Observing Yang-Lee Criticality in Rydberg Atomic Arrays.

Yang-Lee edge singularities (YLES) are the edges of the partition function zeros of an interacting spin model in the space of complex control parameters. They play an important role in understanding non-Hermitian phase transitions in many-body physics, as well as characterizing the corresponding nonunitary criticality. Even though such partition function zeroes have been measured in dynamical experiments where time acts as the imaginary control field, experimentally demonstrating such YLES criticality with a physical imaginary field has remained elusive due to the difficulty of physically realizing non-Hermitian many-body models. We provide a protocol for observing the YLES by detecting kinked dynamical magnetization responses due to broken PT symmetry, thus enabling the physical probing of nonunitary phase transitions in nonequilibrium settings. In particular, scaling analyses based on our nonunitary time evolution circuit with matrix product states accurately recover the exponents uniquely associated with the corresponding nonunitary CFT. We provide an explicit proposal for observing YLES criticality in Floquet quenched Rydberg atomic arrays with laser-induced loss, which paves the way towards a universal platform for simulating non-Hermitian many-body dynamical phenomena.

Terminally Chlorinated and Thiophene-linked Acceptor-Donor-Acceptor Structured 3D Acceptors with Versatile Processability for High-efficiency Organic Solar Cells.

To exploit the potential of our newly developed three-dimensional (3D) dimerized acceptors, a series of chlorinated 3D acceptors (namely CH8-3/4/5) were reported by precisely tuning the position of chlorine (Cl) atom. The introduction of Cl atom in central unit affects the molecular conformation. Whereas, by replacing fluorinated terminal groups (CH8-3) with chlorinated terminal groups (CH8-4 and CH8-5), the red-shift absorption and enhanced crystallization are achieved. Benefiting from these, all devices received promising power conversion efficiencies (PCEs) over 16 % as well as decent thermal/photo-stabilities. Among them, PM6:CH8-4 based device yielded a best PCE of 17.58 %. Besides, the 3D merits with multi alkyl chains enable their versatile processability during the device preparation. Impressive PCEs of 17.27 % and 16.23 % could be achieved for non-halogen solvent processable devices prepared in glovebox and ambient, respectively. 2.88 cm2 modules also obtained PCEs over 13 % via spin-coating and blade-coating methods, respectively. These results are among the best performance of dimerized acceptors. The decent performance of CH8-4 on small-area devices, modules and non-halogen solvent-processed devices highlights the versatile processing capability of our 3D acceptors, as well as their potential applications in the future.

Bayesian network mediation analysis with application to the brain functional connectome.

The brain functional connectome, the collection of interconnected neural circuits along functional networks, facilitates a cutting-edge understanding of brain functioning, and has a potential to play a mediating role within the effect pathway between an exposure and an outcome. While existing mediation analytic approaches are capable of providing insight into complex processes, they mainly focus on a univariate mediator or mediator vector, without considering network-variate mediators. To fill the methodological gap and accomplish this exciting and urgent application, in the article, we propose an integrative mediation analysis under a Bayesian paradigm with networks entailing the mediation effect. To parameterize the network measurements, we introduce individually specified stochastic block models with unknown block allocation, and naturally bridge effect elements through the latent network mediators induced by the connectivity weights across network modules. To enable the identification of truly active mediating components, we simultaneously impose a feature selection across network mediators. We show the superiority of our model in estimating different effect components and selecting active mediating network structures. As a practical illustration of this approach's application to network neuroscience, we characterize the relationship between a therapeutic intervention and opioid abstinence as mediated by brain functional sub-networks.

Highly Sensitive Artificial Visual Array Using Transistors Based on Porphyrins and Semiconductors.

Artificial visual systems with image sensing and storage functions have considerable potential in the field of artificial intelligence. Light-stimulated synaptic devices can be applied for neuromorphic computing to build artificial visual systems. Here, optoelectronic synaptic transistors based on 5,15-(2-hydroxyphenyl)-10,20-(4-nitrophenyl)porphyrin (TPP) and dinaphtho[2,3-b:2',3'-f ]thieno[3,2-b]thiophene (DNTT) are demonstrated. By utilizing stable TPP with high light absorption, the number of photogenerated carriers in the transport layer can be increased significantly. The devices exhibit high photosensitivity and tunable synaptic plasticity. The synaptic weight can be effectively modulated by the intensity, width, and wavelength of the light signals. Due to the high light absorption of TPP, an ultrasensitive artificial visual array based on these devices is developed, which can detect weak light signals as low as 1 µW cm-2 . Low-voltage operation is further demonstrated. Even with applied voltages as low as -70 µV, the devices can still show obvious responses, leading to an ultralow energy consumption of 1.4 fJ. The devices successfully demonstrate image sensing and storage functions, which can accurately identify visual information. In addition, the devices can preprocess information and achieve noise reduction. The excellent synaptic behavior of the TPP-based electronics suggests their good potential in the development of new intelligent visual systems.

Degradable Photonic Synaptic Transistors Based on Natural Biomaterials and Carbon Nanotubes.

Artificial synaptic devices have potential for overcoming the bottleneck of von Neumann architecture and building artificial brain-like computers. Up to now, developing synaptic devices by utilizing biocompatible and biodegradable materials in electronic devices has been an interesting research direction due to the requirements of sustainable development. Here, a degradable photonic synaptic device is reported by combining biomaterials chlorophyll-a and single-walled carbon nanotubes (SWCNTs). Several basic synaptic functions, including excitatory postsynaptic current (EPSC), paired pulse facilitation (PPF), transition from short-term memory (STM) to long-term memory (LTM), and learning and forgetting behaviors, are successfully emulated through the chlorophyll-a/SWCNTs synaptic device. Furthermore, decent synaptic behaviors can still be achieved at a low drain voltage of -0.0001 V, which results in quite low energy consumption of 17.5 fJ per pulse. Finally, the degradability of this chlorophyll-a/SWCNTs transistor array is demonstrated, indicating that the device can be environmentally friendly. This work provides a new guide to the development of next-generation green and degradable neuromorphic computing electronics.

circMYBL2, a circRNA from MYBL2, regulates FLT3 translation by recruiting PTBP1 to promote FLT3-ITD AML progression.

Internal tandem duplication (ITD) mutations within FMS-like tyrosine kinase-3 (FLT3) occur in up to 30% of acute myeloid leukemia (AML) patients and confer a very poor prognosis. The oncogenic form of FLT3 is an important therapeutic target, and inhibitors specifically targeting FLT3 kinase can induce complete remission; however, relapse after remission has been observed due to acquired resistance with secondary mutations in FLT3, highlighting the need for new strategies to target FLT3-ITD mutations. Recent studies have reported that the aberrant formations of circular RNAs (circRNAs) are biological tumorigenesis-relevant mechanisms and potential therapeutic targets. Herein, we discovered a circRNA, circMYBL2, derived from the cell-cycle checkpoint gene MYBL2. circMYBL2 is more highly expressed in AML patients with FLT3-ITD mutations than in those without the FLT3-ITD mutation. We found that circMYBL2 knockdown specifically inhibits proliferation and promotes the differentiation of FLT3-ITD AML cells in vitro and in vivo. Interestingly, we found that circMYBL2 significantly influences the protein level of mutant FLT3 kinase, which contributes to the activation of FLT3-ITD-dependent signaling pathways. Mechanistically, circMYBL2 enhanced the translational efficiency of FLT3 kinase by increasing the binding of polypyrimidine tract-binding protein 1 (PTBP1) to FLT3 messenger RNA. Moreover, circMYBL2 knockdown impaired the cytoactivity of inhibitor-resistant FLT3-ITD+ cells, with a significant decrease in FLT3 kinase expression, followed by the inactivation of its downstream pathways. In summary, we are the first to reveal a circRNA that specifically influences FLT3-ITD AML and regulates FLT3 kinase levels through translational regulation, suggesting that circMYBL2 may be a potential therapeutic target for FLT3-ITD AML.

Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy.

A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring. A quantitative 19-gene digital RNA signature (CTC score) applied to microfluidically enriched CTCs robustly distinguishes melanoma cells, within a background of blood cells in reconstituted and in patient-derived (n = 42) blood specimens. In a prospective cohort of 49 patients treated with immune checkpoint inhibitors, a decrease in CTC score within 7 weeks of therapy correlates with marked improvement in progression-free survival [hazard ratio (HR), 0.17; P = 0.008] and overall survival (HR, 0.12; P = 0.04). Thus, digital quantitation of melanoma CTC-derived transcripts enables serial noninvasive monitoring of tumor burden, supporting the rational application of immune checkpoint inhibition therapies.

[Review on Development of Heart Rate and Respiratory Core Vital Characteristics Monitoring Technology].

Life monitoring technology as the basis of health evaluation, in recent years, its related technology research also has new development, in which cardiopulmonary parameters are the core physiological indicators to measure the basic state of vital signs, the analysis of its monitoring technology is particularly important. In this study, the main means of life monitoring are analyzed, and the monitoring technology of cardiopulmonary parameters is the main focus. What is more, the research status and development of contact and non-contact cardiopulmonary monitoring technology at home and abroad were also considered. Lastly, this study will be combined with the radar wave vital signs monitoring technology, which has been achieved good results in the field of cardiopulmonary monitoring, in order to provide a reference for the long-term development of life monitoring field and the technology integration of intelligent pension, intelligent automobile and other related industries.

Imaging Features and Metastatic Patterns of Advanced ALK-Rearranged Non-Small Cell Lung Cancer.

OBJECTIVE.ALK rearrangements are an established targetable oncogenic driver in non-small cell lung cancer (NSCLC). The goal of this study was to determine the imaging features of the primary tumor and metastatic patterns in advanced ALK-rearranged (ALK+) NSCLC that may be different from those in EGFR-mutant (EGFR+) or EGFR/ALK wild-type (EGFR-/ALK-) NSCLC. MATERIALS AND METHODS. Patients with advanced ALK+, EGFR+, or EGFR-/ALK- NSCLC were retrospectively identified. Two radiologists concurrently assessed the imaging features of the primary tumor and the distribution of metastases in these patients. RESULTS. We identified a cohort of 333 patients with metastatic NSCLC (119 ALK+ cases, 116 EGFR+ cases, and 98 EGFR-/ALK- cases). Compared with EGFR+ and EGFR-/ALK- NSCLC, the primary tumor in ALK+ NSCLC was more likely to be located in the lower lobes (53% of ALK+, 34% of EGFR+, and 36% of EGFR-/ALK- tumors; p < 0.05), less likely to be subsolid (1% of ALK+, 11% of EGFR+, and 8% of EGFR-/ALK- tumors; p < 0.02), and less likely to have air bronchograms (7% of ALK+, 28% of EGFR+, and 29% of EGFR-/ALK- tumors; p < 0.01). Compared with EGFR+ and EGFR-/ALK- tumors, ALK+ tumors had higher frequencies of distant nodal metastasis (20% of ALK+ tumors vs 2% of EGFR+ and 9% of EGFR-/ALK- tumors; p < 0.05) and lymphangitic carcinomatosis (37% of ALK+ tumors vs 12% of EGFR+ and 12% of EGFR-/ALK- tumors; p < 0.01), but ALK+ tumors had a lower frequency of brain metastasis compared with EGFR+ tumors (24% vs 41%; p = 0.01). Although there was no statistically significant difference in the frequencies of bone metastasis among the three groups, sclerotic bone metastases were more common in the ALK+ tumors (22% vs 7% of EGFR+ tumors and 6% of EGFR-/ALK- tumors; p < 0.01). CONCLUSION. Advanced ALK+ NSCLC has primary tumor imaging features and patterns of metastasis that are different from those of EGFR+ or EGFR-/ALK- wild type NSCLC at the time of initial presentation.

3D-Printed Immunosensor Arrays for Cancer Diagnostics.

Detecting cancer at an early stage of disease progression promises better treatment outcomes and longer lifespans for cancer survivors. Research has been directed towards the development of accessible and highly sensitive cancer diagnostic tools, many of which rely on protein biomarkers and biomarker panels which are overexpressed in body fluids and associated with different types of cancer. Protein biomarker detection for point-of-care (POC) use requires the development of sensitive, noninvasive liquid biopsy cancer diagnostics that overcome the limitations and low sensitivities associated with current dependence upon imaging and invasive biopsies. Among many endeavors to produce user-friendly, semi-automated, and sensitive protein biomarker sensors, 3D printing is rapidly becoming an important contemporary tool for achieving these goals. Supported by the widely available selection of affordable desktop 3D printers and diverse printing options, 3D printing is becoming a standard tool for developing low-cost immunosensors that can also be used to make final commercial products. In the last few years, 3D printing platforms have been used to produce complex sensor devices with high resolution, tailored towards researchers' and clinicians' needs and limited only by their imagination. Unlike traditional subtractive manufacturing, 3D printing, also known as additive manufacturing, has drastically reduced the time of sensor and sensor array development while offering excellent sensitivity at a fraction of the cost of conventional technologies such as photolithography. In this review, we offer a comprehensive description of 3D printing techniques commonly used to develop immunosensors, arrays, and microfluidic arrays. In addition, recent applications utilizing 3D printing in immunosensors integrated with different signal transduction strategies are described. These applications include electrochemical, chemiluminescent (CL), and electrochemiluminescent (ECL) 3D-printed immunosensors. Finally, we discuss current challenges and limitations associated with available 3D printing technology and future directions of this field.

Viewing Imaging Studies: How Patient Location and Imaging Site Affect Referring Physicians.

The purpose of this study was to assess if clinical indications, patient location, and imaging sites predict the viewing pattern of referring physicians for CT and MR of the head, chest, and abdomen. Our study included 166,953 CT/MR images of head/chest/abdomen in 2016-2017 in the outpatient (OP, n = 83,981 CT/MR), inpatient (IP, n = 51,052), and emergency (ED, n = 31,920) settings. There were 125,329 CT/MR performed in the hospital setting and 41,624 in one of the nine off-campus locations. We extracted information regarding body region (head/chest/abdomen), patient location, and imaging site from the electronic medical records (EPIC). We recorded clinical indications and the number of times referring physicians viewed CT/MR (defined as the number of separate views of imaging in the EPIC). Data were analyzed with the Microsoft SQL and SPSS statistical software. About 33% of IP CT and MR studies are viewed > 6 times compared to 7% for OP and 19% of ED studies (p < 0.001). Conversely, most OP studies (55%) were viewed 1-2 times only, compared to 21% for IP and 38% for ED studies (p < 0.001). In-hospital exams are viewed (≥ 6 views; 39% studies) more frequently than off-campus imaging (≥ 6 views; 17% studies) (p < 0.001). For head CT/MR, certain clinical indications (i.e., stroke) had higher viewing rates compared to other clinical indications such as malignancy, headache, and dizziness. Conversely, for chest CT, dyspnea-hypoxia had much higher viewing rates (> 6 times) in IP (55%) and ED (46%) than in OP settings (22%). Patient location and imaging site regardless of clinical indications have a profound effect on viewing patterns of referring physicians. Understanding viewing patterns of the referring physicians can help guide interpretation priorities and finding communication for imaging exams based on patient location, imaging site, and clinical indications. The information can help in the efficient delivery of patient care.