Single-domain near-infrared protein provides a scaffold for antigen-dependent fluorescent nanobodies.

Small near-infrared (NIR) fluorescent proteins (FPs) are much needed as protein tags for imaging applications. We developed a 17 kDa NIR FP, called miRFP670nano3, which brightly fluoresces in mammalian cells and enables deep-brain imaging. By exploring miRFP670nano3 as an internal tag, we engineered 32 kDa NIR fluorescent nanobodies, termed NIR-Fbs, whose stability and fluorescence strongly depend on the presence of specific intracellular antigens. NIR-Fbs allowed background-free visualization of endogenous proteins, detection of viral antigens, labeling of cells expressing target molecules and identification of double-positive cell populations with bispecific NIR-Fbs against two antigens. Applying NIR-Fbs as destabilizing fusion partners, we developed molecular tools for directed degradation of targeted proteins, controllable protein expression and modulation of enzymatic activities. Altogether, NIR-Fbs enable the detection and manipulation of a variety of cellular processes based on the intracellular protein profile.

Hospitalizations and Deaths Associated with EVALI.

BACKGROUND: As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC). METHODS: In a national study, we compared the characteristics of patients with fatal cases of EVALI with those of patients with nonfatal cases to improve the ability of clinicians to identify patients at increased risk for death from the condition. Health departments reported cases of EVALI to the CDC and included, when available, data from medical-record abstractions and patient interviews. Analyses included all the patients with fatal or nonfatal cases of EVALI that were reported to the CDC as of January 7, 2020. We also present three case reports of patients who died from EVALI to illustrate the clinical characteristics common among such patients. RESULTS: Most of the patients with fatal or nonfatal cases of EVALI were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively). The proportion of patients with fatal or nonfatal cases was higher among those who were non-Hispanic white (39 of 49 [80%] and 1104 of 1818 [61%], respectively) than among those in other race or ethnic groups. The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]). Among the patients who had an available medical history, a higher proportion of those with fatal cases than those with nonfatal cases had a history of asthma (13 of 57 [23%] vs. 102 of 1297 [8%]), cardiac disease (26 of 55 [47%] vs. 115 of 1169 [10%]), or a mental health condition (32 of 49 [65%] vs. 575 of 1398 [41%]). A total of 26 of 50 patients (52%) with fatal cases had obesity. Half the patients with fatal cases (25 of 54 [46%]) were seen in an outpatient setting before hospitalization or death. CONCLUSIONS: Chronic conditions, including cardiac and respiratory diseases and mental health conditions, were common among hospitalized patients with EVALI.

Cost-utility analysis of shockwave lithotripsy vs ureteroscopic stone treatment in adults.

OBJECTIVES: To assess the cost-effectiveness, resource use implications, quality-adjusted life-years (QALYs) and cost per QALY of care pathways starting with either extracorporeal shockwave lithotripsy (SWL) or with ureteroscopic retrieval (ureteroscopy [URS]) for the management of ureteric stones. PATIENTS AND METHODS: Data on quality of life and resource use for 613 patients, collected prospectively in the Therapeutic Interventions for Stones of the Ureter (TISU) randomized controlled trial (ISRCTN 92289221), were used to assess the cost-effectiveness of two care pathways, SWL and URS. A health provider (UK National Health Service) perspective was adopted to estimate the costs of the interventions and subsequent resource use. Quality-of-life data were calculated using a generic instrument, the EuroQol EQ-5D-3L. Results are expressed as incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS: The mean QALY difference (SWL vs URS) was -0.021 (95% confidence interval [CI] -0.033 to -0.010) and the mean cost difference was -£809 (95% CI -£1061 to -£551). The QALY difference translated into approximately 10 more healthy days over the 6-month period for the patients on the URS care pathway. The probabaility that SWL is cost-effective is 79% at a society's willingness to pay (WTP) threshold for 1 QALY of £30,000 and 98% at a WTP threshold of £20,000. CONCLUSION: The SWL pathway results in lower QALYs than URS but costs less. The incremental cost per QALY is £39 118 cost saving per QALY lost, with a 79% probability that SWL would be considered cost-effective at a WTP threshold for 1 QALY of £30 000 and 98% at a WTP threshold of £20 000. Decision-makers need to determine if costs saved justify the loss in QALYs.

Improving Research Dissemination to Black Sexual Minority Men: Development of a Community-Led and Theory-Based Dissemination Plan.

Background. Although research dissemination to participants and community stakeholders is a fundamental component of translational research, it rarely occurs. The objective of this study was to create a community-led, theory-based dissemination plan to engage local Black sexual minority men in an active dissemination process throughout a sexual health research study. Method. Seven focus groups (N = 38) were conducted with Black, cisgender sexual minority men aged 18 to 45 years. Findings were analyzed through thematic content analysis guided by McGuire's persuasive communication theory. Findings were used to draft a dissemination plan, which was then reviewed and edited by the study's community advisory board (CAB). The plan continues to be updated in response to community needs through CAB discussions. Results. Participants preferred messages concerning syphilis and other health concerns as well as information on local resources. Preferred sources included researchers working with trusted community organizations and leaders. Preferred channels included community events and social media, implemented with consistency. CAB feedback included expanding the target audience of dissemination efforts as well as the development of ideas for channels (i.e., events) and sources (i.e., community organizations and leaders). Additional revisions occurred in response to the COVID-19 pandemic. Conclusion. Given the continued lack of research dissemination to participant and community stakeholders, the process of developing a community-led, theory-based dissemination plan may benefit and help guide researchers to adopt this practice. It is critical that participant and community stakeholder dissemination become more highly prioritized as we strive for public health improvements and the elimination of health disparities.

Generation and detection of spin-orbit coupled neutron beams.

Spin-orbit coupling of light has come to the fore in nanooptics and plasmonics, and is a key ingredient of topological photonics and chiral quantum optics. We demonstrate a basic tool for incorporating analogous effects into neutron optics: the generation and detection of neutron beams with coupled spin and orbital angular momentum. The 3He neutron spin filters are used in conjunction with specifically oriented triangular coils to prepare neutron beams with lattices of spin-orbit correlations, as demonstrated by their spin-dependent intensity profiles. These correlations can be tailored to particular applications, such as neutron studies of topological materials.

Past, present, and future developments in enantioselective analysis using capillary electromigration techniques.

Enantioseparation of chiral products has become increasingly important in a large diversity of academic and industrial applications. The separation of chiral compounds is inherently challenging and thus requires a suitable analytical technique that can achieve high resolution and sensitivity. In this context, CE has shown remarkable results so far. Chiral CE offers an orthogonal enantioselectivity and is typically considered less costly than chromatographic techniques, since only minute amounts of chiral selectors are needed. Several CE approaches have been developed for chiral analysis, including chiral EKC and chiral CEC. Enantioseparations by EKC benefit from the wide variety of possible pseudostationary phases that can be employed. Chiral CEC, on the other hand, combines chromatographic separation principles with the bulk fluid movement of CE, benefitting from reduced band broadening as compared to pressure-driven systems. Although UV detection is conventionally used for these approaches, MS can also be considered. CE-MS represents a promising alternative due to the increased sensitivity and selectivity, enabling the chiral analysis of complex samples. The potential contamination of the MS ion source in EKC-MS can be overcome using partial-filling and counter-migration techniques. However, chiral analysis using monolithic and open-tubular CEC-MS awaits additional method validation and a dedicated commercial interface. Further efforts in chiral CE are expected toward the improvement of existing techniques, the development of novel pseudostationary phases, and establishing the use of chiral ionic liquids, molecular imprinted polymers, and metal-organic frameworks. These developments will certainly foster the adoption of CE(-MS) as a well-established technique in routine chiral analysis.

Controlling neutron orbital angular momentum.

The quantized orbital angular momentum (OAM) of photons offers an additional degree of freedom and topological protection from noise. Photonic OAM states have therefore been exploited in various applications ranging from studies of quantum entanglement and quantum information science to imaging. The OAM states of electron beams have been shown to be similarly useful, for example in rotating nanoparticles and determining the chirality of crystals. However, although neutrons--as massive, penetrating and neutral particles--are important in materials characterization, quantum information and studies of the foundations of quantum mechanics, OAM control of neutrons has yet to be achieved. Here, we demonstrate OAM control of neutrons using macroscopic spiral phase plates that apply a 'twist' to an input neutron beam. The twisted neutron beams are analysed with neutron interferometry. Our techniques, applied to spatially incoherent beams, demonstrate both the addition of quantum angular momenta along the direction of propagation, effected by multiple spiral phase plates, and the conservation of topological charge with respect to uniform phase fluctuations. Neutron-based studies of quantum information science, the foundations of quantum mechanics, and scattering and imaging of magnetic, superconducting and chiral materials have until now been limited to three degrees of freedom: spin, path and energy. The optimization of OAM control, leading to well defined values of OAM, would provide an additional quantized degree of freedom for such studies.

Radiographic Evaluation of Proximal Femoral Nutrient Arteries After Total Hip Arthroplasty With a Short Femoral Stem.

BACKGROUND: The use of less invasive approaches and broach only press-fit femoral stems in total hip arthroplasty (THA) may increase the risk for periprosthetic fracture. Proximal femoral nutrient arteries (FNAs) can be mistaken for fractures after THA. Description of FNAs in relation to THA implants is important to better distinguish between FNAs and periprosthetic fractures. The purpose of this study was to evaluate the frequency, location, and morphology of FNAs visible on radiographs after primary THA with a broach-only stem design. METHODS: A retrospective cohort study was performed. Patients ≥18 years who underwent primary THA with a cementless, broach-only stem, and had 6-week follow-up radiographs were included. Patient demographics were recorded. Anteroposterior and lateral radiographs at 6 weeks postoperatively were assessed for the presence of FNA; if present, measurements of vessel location and morphology were obtained. Descriptive statistics were reported. Univariate and multivariate analyses were performed to identify patient characteristics associated with the radiographic presence of perforating vessel. RESULTS: A total of 378 hips were evaluated (332 patients). FNAs were identified radiographically in 46.3% (175 hips/378 hips). All FNAs were found to be unicortical, most observed in the posterior and lateral cortices. Gender, age, BMI, stem position, and surgical approach did not correlate with a presence of FNA on radiograph. CONCLUSION: FNA was seen on postoperative radiographs in 46% of patients after THA with one broach-only stem design. The FNA was unicortical and present on preoperative radiographs. Surgeons should consider this when evaluating postoperative radiographs.

Recommendations From Black Sexual Minority Men: Building Trust to Improve Engagement and Impact of HIV/STI Research.

As demonstrated by the consistently documented disproportionately high rates of HIV and STIs (sexually transmitted infections) among Black sexual minority men (BSMM), current efforts to develop responsive interventions to reduce HIV and other STIs within this population have not been sufficient. It is therefore critical that public health researchers reflect meaningfully on the ways in which they investigate HIV and STIs. Engagement with BSMM is crucial in addressing the disproportionately high rates of HIV and STIs experienced, and thus the goal of the current research was to identify community-developed strategies that may enhance community engagement in research with BSMM. Seven focus groups (N = 38) were held with cisgender BSMM ages 18 to 45 years in Baltimore, Maryland to explore how to better engage this population and improve HIV and STI research. Data analysis of the text was conducted using an iterative, thematic constant comparison process informed by grounded theory. Four distinct themes related to trust-building within the broader community emerged: (1) authentic engagement with the community, (2) increased transparency of the research process, (3) capacity building of research staff from the community, and (4) a balance of research and action. Strategies for researchers to build community trust were identified that are related to, but slightly distinct from, common discussions in the community engaged research literature that are centered more specifically on trust-building within community-academic partnerships. Engagement with BSMM is crucial in addressing HIV and STI health disparities. It is critical that community engagement also be a priority to policy makers, research institutions, and funding institutions.

Characteristics of Persons Who Died with COVID-19 - United States, February 12-May 18, 2020.

During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).

Discovery and structure activity relationships of 7-benzyl triazolopyridines as stable, selective, and reversible inhibitors of myeloperoxidase.

Myeloperoxidase (MPO) is a heme peroxidase found in neutrophils, monocytes and macrophages that efficiently catalyzes the oxidation of endogenous chloride into hypochlorous acid for antimicrobial activity. Chronic MPO activation can lead to indiscriminate protein modification causing tissue damage, and has been associated with chronic inflammatory diseases, atherosclerosis, and acute cardiovascular events. Triazolopyrimidine 5 is a reversible MPO inhibitor; however it suffers from poor stability in acid, and is an irreversible inhibitor of the DNA repair protein methyl guanine methyl transferase (MGMT). Structure-based drug design was employed to discover benzyl triazolopyridines with improved MPO potency, as well as acid stability, no reactivity with MGMT, and selectivity against thyroid peroxidase (TPO). Structure-activity relationships, a crystal structure of the MPO-inhibitor complex, and acute in vivo pharmacodynamic data are described herein.

Hysteresis in a quantized superfluid 'atomtronic' circuit.

Atomtronics is an emerging interdisciplinary field that seeks to develop new functional methods by creating devices and circuits where ultracold atoms, often superfluids, have a role analogous to that of electrons in electronics. Hysteresis is widely used in electronic circuits-it is routinely observed in superconducting circuits and is essential in radio-frequency superconducting quantum interference devices. Furthermore, it is as fundamental to superfluidity (and superconductivity) as quantized persistent currents, critical velocity and Josephson effects. Nevertheless, despite multiple theoretical predictions, hysteresis has not been previously observed in any superfluid, atomic-gas Bose-Einstein condensate. Here we directly detect hysteresis between quantized circulation states in an atomtronic circuit formed from a ring of superfluid Bose-Einstein condensate obstructed by a rotating weak link (a region of low atomic density). This contrasts with previous experiments on superfluid liquid helium where hysteresis was observed directly in systems in which the quantization of flow could not be observed, and indirectly in systems that showed quantized flow. Our techniques allow us to tune the size of the hysteresis loop and to consider the fundamental excitations that accompany hysteresis. The results suggest that the relevant excitations involved in hysteresis are vortices, and indicate that dissipation has an important role in the dynamics. Controlled hysteresis in atomtronic circuits may prove to be a crucial feature for the development of practical devices, just as it has in electronic circuits such as memories, digital noise filters (for example Schmitt triggers) and magnetometers (for example superconducting quantum interference devices).

Extreme ultraviolet photon conversion efficiency of tetraphenyl butadiene.

Extreme ultraviolet (EUV) radiation can be converted to visible light using tetraphenyl butadiene (TPB) as a phosphor. 1 µm films of TPB were prepared using thermal vapor deposition of the pure material and by spin coating suspensions of TPB in high-molecular-weight polystyrene/toluene solutions. Calibrated sources and detectors were used to determine the effective photon conversion efficiency of the films for incident EUV radiation in the wavelength range of $125\;{\rm nm}\le\lambda\le 200\;{\rm nm}$125nm≤λ≤200nm. After exposure to atmosphere, the efficiency of the vapor-deposited films decreased significantly, while the efficiency of the spin-coated films remained unchanged. The production of TPB films by spin coating offers the advantages of simplicity and long-term stability.

Isolation of a Low Number of Sperm Cells from Female DNA in a Glass-PDMS-Glass Microchip via Bead-Assisted Acoustic Differential Extraction.

We report an improved separation method for the isolation of sperm cells from dilute, "large volume" samples containing female DNA using bead-assisted acoustic trapping. In an enclosed glass-PDMS-glass (GPG) resonator, we exploit a three-layer microfluidic architecture to generate "trapping nodes" in ultrasonic standing waves. We investigate the dependence of trapping efficiency on particle concentration for both sperm cells and polymeric beads. After determination of the critical concentration of polymeric beads required to seed the trapping event, sperm cells in dilute solution are trapped as a result of the enhanced secondary radiation force (SRF). Sperm-cell-containing samples with volumes up to 300 µL and cell concentrations as low as ∼10 cells/µL are amenable to effective trapping in the presence of an abundance of female DNA in solution. Complete processing of samples is accomplished with separation of the female and male fractions within 15 min. We demonstrate that the collected fractions are amenable to subsequent DNA extraction, short tandem repeat PCR, and the generation of STR profiles for the isolated sperm cells.

Patient Characteristics and Product Use Behaviors Among Persons with E-cigarette, or Vaping, Product Use-Associated Lung Injury - Indiana, June ̶ October 2019.

As of December 4, 2019, a total of 2,291 cases of hospitalized e-cigarette, or vaping, product use-associated lung injury (EVALI) have been reported from 50 states, the District of Columbia, and two U.S. territories (Puerto Rico and the U.S. Virgin Islands) (1). State health departments, including the Indiana State Department of Health (ISDH), are working with their local health departments and with CDC, the Food and Drug Administration, and other clinical and public health partners in investigating this outbreak of EVALI. On August 7, 2019, ISDH issued an advisory regarding patients hospitalized in Wisconsin with severe acute lung injury who reported the use of e-cigarette, or vaping, products (2); health care providers were requested to notify ISDH of similar cases. On August 8, 2019, ISDH received reports of five similar cases among Indiana residents. Suspected cases EVALI reported to ISDH were investigated further only among patients who required hospitalization. Established case definitions were used to classify cases.* Medical record abstractions and patient interviews were completed using nationally standardized forms to ascertain patient characteristics, medical care received, and product-use behaviors.

Structure based design of macrocyclic factor XIa inhibitors: Discovery of cyclic P1 linker moieties with improved oral bioavailability.

This manuscript describes the discovery of a series of macrocyclic inhibitors of FXIa with oral bioavailability. Assisted by structure based drug design and ligand bound X-ray crystal structures, the group linking the P1 moiety to the macrocyclic core was modified with the goal of reducing H-bond donors to improve pharmacokinetic performance versus 9. This effort resulted in the discovery of several cyclic P1 linkers, exemplified by 10, that are constrained mimics of the bioactive conformation displayed by the acrylamide linker of 9. These cyclic P1 linkers demonstrated enhanced bioavailability and improved potency.

Generation of a Lattice of Spin-Orbit Beams via Coherent Averaging.

We describe a highly robust method, applicable to both electromagnetic and matter-wave beams, that can produce a beam consisting of a lattice of orbital angular momentum (OAM) states coupled to a two-level system. We also define efficient protocols for controlling and manipulating the lattice characteristics. These protocols are applied in an experimental realization of a lattice of optical spin-orbit beams. The novel passive devices we demonstrate here are also a natural alternative to existing methods for producing single-axis OAM and spin-orbit beams. Our techniques provide new tools for investigations of chiral and topological materials with light and particle beams.

Increasing Perioperative Communication With Automated Mobile Phone Messaging in Total Joint Arthroplasty.

BACKGROUND: Automated mobile phone messaging has not been reported in total joint arthroplasty (TJA). Our purpose was to compare Press Ganey (PG) and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores between TJA patients who did and did not receive perioperative automated mobile phone messages. METHODS: Patients were prospectively enrolled and received messages for 1 week prior until 2 weeks after TJA. Message content included reminders, activity, and pain control. Patients answered select PG/HCAHPS and questions regarding their experience with the automated communication platform. Average PG/HCAHPS scores were compared to historical TJA patients in the 3-year window prior (control group) with significance P < .05. RESULTS: Thirty-seven consecutive patients were approached and 92% (n = 34) were enrolled. The experimental group was 47% male, with 80% patients between 51 and 75 years. The experimental (n = 30) and control groups (n = 26) were similar. Patients receiving messages were more likely to have a good understanding of health responsibilities (P = .024) and feel that the care team demonstrated shared decision-making (P = .024). Of patients enrolled, 87% felt messages helped them be more prepared for surgery, 100% felt messages kept them better informed, and 97% would participate again. CONCLUSION: TJA patients who received perioperative communication via automated mobile phone messaging had improved patient satisfaction scores postoperatively. Patients perceived this form of communication was useful and kept them better informed. Automated mobile phone messaging can be an easily integrated, helpful adjunct to surgeons, healthcare systems, and case managers to more effectively communicate with patients undergoing TJA in this era of value-based care.

Methods for preparation and detection of neutron spin-orbit states.

The generation and control of neutron orbital angular momentum (OAM) states and spin correlated OAM (spin-orbit) states provides a powerful probe of materials with unique penetrating abilities and magnetic sensitivity. We describe techniques to prepare and characterize neutron spin-orbit states, and provide a quantitative comparison to known procedures. The proposed detection method directly measures the correlations of spin state and transverse momentum, and overcomes the major challenges associated with neutrons, which are low flux and small spatial coherence length. Our preparation techniques, utilizing special geometries of magnetic fields, are based on coherent averaging and spatial control methods borrowed from nuclear magnetic resonance. The described procedures may be extended to other probes such as electrons and electromagnetic waves.