Quantitative Characterization of Respiratory Patterns on Dynamic Higher Temporal Resolution MRI to Stratify Postacute Covid-19 Patients by Cardiopulmonary Symptom Burden.

BACKGROUND: Postacute Covid-19 patients commonly present with respiratory symptoms; however, a noninvasive imaging method for quantitative characterization of respiratory patterns is lacking. PURPOSE: To evaluate if quantitative characterization of respiratory pattern on free-breathing higher temporal resolution MRI stratifies patients by cardiopulmonary symptom burden. STUDY TYPE: Prospective analysis of retrospectively acquired data. SUBJECTS: A total of 37 postacute Covid-19 patients (25 male; median [interquartile range (IQR)] age: 58 [42-64] years; median [IQR] days from acute infection: 335 [186-449]). FIELD STRENGTH/SEQUENCE: 0.55 T/two-dimensional coronal true fast imaging with steady-state free precession (trueFISP) at higher temporal resolution. ASSESSMENT: Patients were stratified into three groups based on presence of no (N = 11), 1 (N = 14), or ≥2 (N = 14) cardiopulmonary symptoms, assessed using a standardized symptom inventory within 1 month of MRI. An automated lung postprocessing workflow segmented each lung in each trueFISP image (temporal resolution 0.2 seconds) and respiratory curves were generated. Quantitative parameters were derived including tidal lung area, rates of inspiration and expiration, lung area coefficient of variability (CV), and respiratory incoherence (departure from sinusoidal pattern) were. Pulmonary function tests were recorded if within 1 month of MRI. Qualitative assessment of respiratory pattern and lung opacity was performed by three independent readers with 6, 9, and 23 years of experience. STATISTICAL TESTS: Analysis of variance to assess differences in demographic, clinical, and quantitative MRI parameters among groups; univariable analysis and multinomial logistic regression modeling to determine features predictive of patient symptom status; Akaike information criterion to compare the quality of regression models; Cohen and Fleiss kappa (κ) to quantify inter-reader reliability. Two-sided 5% significance level was used. RESULTS: Tidal area and lung area CV were significantly higher in patients with two or more symptoms than in those with one or no symptoms (area: 15.4 cm2 vs. 12.9 cm2 vs. 12.8 cm2 ; CV: 0.072, 0.067, and 0.058). Respiratory incoherence was significantly higher in patients with two or more symptoms than in those with one or no symptoms (0.05 vs. 0.043 vs. 0.033). There were no significant differences in patient age (P = 0.19), sex (P = 0.88), lung opacity severity (P = 0.48), or pulmonary function tests (P = 0.35-0.97) among groups. Qualitative reader assessment did not distinguish between groups and showed slight inter-reader agreement (κ = 0.05-0.11). DATA CONCLUSION: Quantitative respiratory pattern measures derived from dynamic higher-temporal resolution MRI have potential to stratify patients by symptom burden in a postacute Covid-19 cohort. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Block copolymer self-assembly derived mesoporous magnetic materials with three-dimensionally (3D) co-continuous gyroid nanostructure.

Magnetic nanomaterials are gaining interest for their many applications in technological areas from information science and computing to next-generation quantum energy materials. While magnetic materials have historically been nanostructured through techniques such as lithography and molecular beam epitaxy, there has recently been growing interest in using soft matter self-assembly. In this work, a triblock terpolymer, poly(isoprene-block-styrene-block-ethylene oxide) (ISO), is used as a structure directing agent for aluminosilicate sol nanoparticles and magnetic material precursors to generate organic-inorganic bulk hybrid films with co-continuous morphology. After thermal processing into mesoporous materials, results from a combination of small angle X-ray scattering (SAXS) and scanning electron microscopy (SEM) are consistent with the double gyroid morphology. Nitrogen sorption measurements reveal a type IV isotherm with H1 hysteresis, and yield a specific surface area of around 200 m2 g-1 and an average pore size of 23 nm. The magnetization of the mesostructured material as a function of applied field shows magnetic hysteresis and coercivity at 300 K and 10 K. Comparison of magnetic measurements between the mesoporous gyroid and an unstructured bulk magnetic material, derived from the identical inorganic precursors, reveals the structured material exhibits a coercivity of 250 Oe, opposed to 148 Oe for the unstructured at 10 K, and presence of remnant magnetic moment not conventionally found in bulk hematite; both of these properties are attributed to the mesostructure. This scalable route to mesoporous magnetic materials with co-continuous morphologies from block copolymer self-assembly may provide a pathway to advanced magnetic nanomaterials with a range of potential applications.

Low Field MRI Surveillance 6-24 Months Post-acute COVID-19 Pneumonia: Factors Influencing Severity and Evolution of Lung Opacities.

RATIONALE AND OBJECTIVES: To determine factors influencing low-field MRI lung opacity severity 6-24 months after acute Covid-19 pneumonia. MATERIALS AND METHODS: 104 post-acute Covid-19 patients with 167 MRI exams were included. 32 patients had more than one exam, and 63 exams were serial exams. Pulmonary findings were graded on a scale of 0-4 by quadrant, total score ranging from 0 (no opacity) to 16 (opacity > 75%), and score >8 considered moderate and >12 severe opacity. Kruskal-Wallis, Mann-Whitney, and Spearman rank correlation was used to assess the association of clinical and demographic factors with MR opacity severity at time intervals from acute infection. Random coefficients regression was used to assess whether opacity score changed over time. RESULTS: Severity of initial illness was associated with increased MR opacity score at timeframes up to 24 months (p < .05). Among the 167 exams, moderate to severe MR opacities (total opacity score >8) were identified in 33% of exams beyond 6 months: 37% at 6 - <12 months (n = 23/63); 31% at 12- < 18 months (n = 13/42); 25% at 18- < 24 months (n = 6/24); and 50% at > 24 months (n = 3/6). No significant change in total opacity score over time was identified by random coefficients regression. Among the 32 patients with serial exams, 11 demonstrated no change in opacity score from initial to final exam, 10 decrease in score (mean 2.3, stdev 1.25, range 1-4), and 11 increase in score (average 2.8, stdev 1.48, range 1-7). CONCLUSION: Initial Covid-19 disease severity was associated with increased MRI total opacity score at time intervals up to 24 months, and moderate to severe opacities were commonly identified by low-field MRI beyond 6 months from acute illness.

Retraction to keratin 17 is an imaging biomarker in lung cancers.

[This retracts the article DOI: 10.21037/jtd.2019.08.33.].

The Perfect Cup? Coffee-Derived Polyphenols and Their Roles in Mitigating Factors Affecting Type 2 Diabetes Pathogenesis.

Type 2 diabetes (T2D) is a growing health concern with an estimated 462 million people having been diagnosed worldwide. T2D is characterized by chronically elevated blood glucose and insulin resistance, which culminate in a diminished function of the ß-cell mass in its later stages. This can be perpetuated by and result in inflammation, excess reactive oxygen species production, obesity, and the dysregulation of multiple cellular pathways. Many naturally occurring small molecules have been investigated in terms of their roles in modulating glucose homeostasis and ß-cell function. Many of these compounds can be found in commonly used sources of food and drink. Interestingly, a correlation has been observed between coffee consumption and T2D incidence. However, the specific compounds responsible for this correlation and their mechanisms are still somewhat undetermined. This paper reviews recent research findings on the effects of several polyphenols that are either found in coffee or are metabolites of compounds found in coffee (enterodiol, enterolactone, matairesinol, secoisolariciresinol, kaempferol, quercetin, and chlorogenic acid) on glucose homeostasis and health complications associated with glucose dysregulation, with a special emphasis on their potential anti-diabetic effects. The factors that affect polyphenol content in coffee are also addressed.

Perplexing EPR Signals from 5f36d1 U(II) Complexes.

Metal complexes with unpaired electrons in orbitals of different angular momentum quantum numbers (e.g., f and d orbitals) are unusual and opportunities to study the interactions among these electrons are rare. X-band electron paramagnetic resonance (EPR) data were collected at <10 and 77 K on 10 U(II) complexes with 5f36d1 electron configurations and on some analogous Ce(II), Pr(II), and Nd(II) complexes with 4fn5d1 electron configurations. The U(II) compounds unexpectedly display similar two-line axial signals with g|| = 2.04 and g⊥ = 2.00 at 77 K. In contrast, U(II) complexes with 5f4 configurations are EPR-silent. Unlike U(II), the congenic 4f35d1 Nd(II) complex is EPR-silent. The Ce(II) complex with a 4f15d1 configuration is also EPR-silent, but a signal is observed for the Pr(II) complex, which has a 4f25d1 configuration. Whether or not an EPR signal is expected for these complexes depends on the coupling between f and d electrons. Since the coupling in U(II) systems is expected to be sufficiently strong to preclude an EPR signal from compounds with a 5f36d1 configuration, the results are viewed as unexplained phenomena. However, they do show that 5f36d1 U(II) samples can be differentiated from 5f4 U(II) complexes by EPR spectroscopy.

Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core-Shell Silica Nanoparticles.

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C' dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C' dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C' dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.

Structure-Based Discovery of Potent, Orally Bioavailable Benzoxazepinone-Based WD Repeat Domain 5 Inhibitors.

The chromatin-associated protein WDR5 (WD repeat domain 5) is an essential cofactor for MYC and a conserved regulator of ribosome protein gene transcription. It is also a high-profile target for anti-cancer drug discovery, with proposed utility against both solid and hematological malignancies. We have previously discovered potent dihydroisoquinolinone-based WDR5 WIN-site inhibitors with demonstrated efficacy and safety in animal models. In this study, we sought to optimize the bicyclic core to discover a novel series of WDR5 WIN-site inhibitors with improved potency and physicochemical properties. We identified the 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one core as an alternative scaffold for potent WDR5 inhibitors. Additionally, we used X-ray structural analysis to design partially saturated bicyclic P7 units. These benzoxazepinone-based inhibitors exhibited increased cellular potency and selectivity and favorable physicochemical properties compared to our best-in-class dihydroisoquinolinone-based counterparts. This study opens avenues to discover more advanced WDR5 WIN-site inhibitors and supports their development as novel anti-cancer therapeutics.

Characterization of a Putative New Member of the Genus Potyvirus from Kudzu (Pueraria montana var. lobata) in Mississippi.

Kudzu (Pueraria montana var. lobata), a plant native to Southeastern Asia, has become a major noxious weed covering millions of hectares in the Southern United States. A kudzu patch displaying virus-like symptoms located in Ackerman, northeastern Mississippi (MS), was used as a source for virus isolation and characterization involving mechanical and vector transmission, ultrastructural observation, surveys, Sanger and high-throughput genome sequencing, and sequence analyses. The results revealed the presence of a new potyvirus in infected kudzu, closely related to wisteria vein mosaic virus (WVMV) and provisionally named kudzu chlorotic ring blotch virus (KudCRBV). Genome features and pairwise comparison with six WVMV genomes currently available in GenBank and three additional isolates from MS sequenced in this work suggest that KudCRBV is likely a member of a new species in the genus Potyvirus. Furthermore, under experimental conditions, KudCRBV was successfully transmitted by cotton and potato aphids and mechanically to soybean and beans. A state-wide survey revealed several kudzu patches infected by the virus in northern MS.

Differentiating Imaging Features of Post-lobectomy Right Middle Lobe Torsion.

PURPOSE: The purpose of this study was to identify differences in imaging features between patients with confirmed right middle lobe (RML) torsion compared to those suspected yet without torsion. MATERIALS AND METHODS: This retrospective study entailing a search of radiology reports from April 1, 2014, to April 15, 2021, resulted in 52 patients with suspected yet without lobar torsion and 4 with confirmed torsion, supplemented by 2 additional cases before the search period for a total of 6 confirmed cases. Four thoracic radiologists (1 an adjudicator) evaluated chest radiographs and computed tomography (CT) examinations, and Fisher exact and Mann-Whitney tests were used to identify any significant differences in imaging features (P<0.05). RESULTS: A reversed halo sign was more frequent for all readers (P=0.001) in confirmed RML torsion than patients without torsion (83.3% vs. 0% for 3 readers, one the adjudicator). The CT coronal bronchial angle between RML bronchus and bronchus intermedius was larger (P=0.035) in torsion (121.28 degrees) than nontorsion cases (98.26 degrees). Patients with torsion had a higher percentage of ground-glass opacity in the affected lobe (P=0.031). A convex fissure towards the adjacent lobe on CT (P=0.009) and increased lobe volume on CT (P=0.001) occurred more often in confirmed torsion. CONCLUSION: A reversed halo sign, larger CT coronal bronchial angle, greater proportion of ground-glass opacity, fissural convexity, and larger lobe volume on CT may aid in early recognition of the rare yet highly significant diagnosis of lobar torsion.

Pulmonary Cryoablation Outcomes in Octogenarians and Nonagenarians with Primary Lung Cancer.

PURPOSE: To characterize the effectiveness, safety, and length of stay (LOS) associated with pulmonary cryoablation for management of primary lung malignancies in patients aged ≥80 years. MATERIALS AND METHODS: A retrospective single-center database was compiled of all consecutive patients aged ≥80 years who underwent percutaneous computed tomography-guided cryoablation using modified triple-freeze protocol (1-3 ablation probes) for Stage IA-IIB primary lung malignancies between March 2017 and March 2020 (n = 19; 53% women; mean age, 85 years ± 3.5; range, 80-94 years). Follow-up imaging was assessed for local recurrence. Adverse events and LOS were recorded from chart review. Kaplan-Meier analysis was performed to assess both overall and local recurrence-free survival. RESULTS: Mean patient follow-up period was 21.6 months ± 10.8, and mean imaging follow-up period was 19.2 months ± 9.6. Overall survival at 3 years was 94% (95% CI, 81%-100%). Local recurrence-free survival was 100% throughout the imaging follow-up period. Intraprocedural pneumothorax occurred in 37% (7 of 19) of patients; pneumothorax risk was significantly associated with increased tumor distance from pleura (odds ratio, 1.2; P = .018). Sixty-three percent (12 of 19) of patients were discharged on the day of the procedure, with a mean LOS of 7.7 hours ± 1.6, whereas 37% of patients required overnight observation (2 of 19) or admission (5 of 19), with a mean LOS of 48.1 hours ± 19.4. Overall LOS for all patients was 22.6 hours ± 22.9. CONCLUSIONS: Percutaneous cryoablation of primary pulmonary malignancies can be performed in select octogenarians and nonagenarians with high 3-year overall and recurrence-free survival. Despite nonnegligible risk of pneumothorax, most patients are discharged on the day of the procedure.

Leflutrozole in male obesity-associated hypogonadotropic hypogonadism: Ph 2b double-blind randomised controlled trial.

OBJECTIVE: Assessment of the efficacy and safety/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH). DESIGN: Placebo-controlled, double-blind, RCT, in 70 sites in Europe/USA. METHODS: Patient inclusion criteria: men with BMI of 30-50 kg/m2, morning total testosterone (TT) < 10.41 nmol/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1/0.3/1.0 mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in ≥75% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH/FSH. Safety was assessed through adverse events and laboratory monitoring. RESULTS AND CONCLUSIONS: Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1 kg/m2 and TT 7.97 nmol/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35 nmol/L, for leflutrozole 0.1 mg, 0.3 mg, and 1.0 mg groups respectively, vs 8.04 nmol/L for placebo. LH/FSH significantly increased in leflutrozole vs placebo groups. No improvements in body composition or sexual dysfunction were observed. Semen volume/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean -1.24%, -1.30%, -2.09%) and 0.66% for 0.1 mg, 0.3 mg, 1.0 mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH/LH and semen parameter changes support that leflutrozole may preserve/improve testicular function. CLINICAL TRIAL REGISTRATION NUMBER: NCT02730169.

OME-Zarr: a cloud-optimized bioimaging file format with international community support.

A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself-OME-Zarr-along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain-the file format that underlies so many personal, institutional, and global data management and analysis tasks.

Evaluation of Socioeconomic Disparities in Follow-Up Completion for Incidental Pulmonary Nodules.

PURPOSE: The aim of this study was to evaluate the association between census tract-level measures of social vulnerability and residential segregation and incidental pulmonary nodule (IPN) follow-up. METHODS: This retrospective cohort study included patients with IPNs ≥6 mm in size or multiple subsolid or ground-glass IPNs <6 mm (with nonoptional follow-up recommendations) diagnosed between January 1, 2018, and December 30, 2019, at a large urban tertiary center and followed for ≥2 years. Geographic sociodemographic context was characterized by the 2018 Centers for Disease Control and Prevention Social Vulnerability Index (SVI) and the index of concentration at the extremes (ICE), categorized in quartiles. Multivariable binomial regression models were used, with a primary outcome of inappropriate IPN follow-up (late or no follow-up). Models were also stratified by nodule risk. RESULTS: The study consisted of 2,492 patients (mean age, 65.6 ± 12.6 years; 1,361 women). Top-quartile SVI patients were more likely to have inappropriate follow-up (risk ratio [RR], 1.24; 95% confidence interval [CI], 1.12-1.36) compared with the bottom quartile; risk was also elevated in top-quartile SVI subcategories of socioeconomic status (RR, 1.23; 95% CI, 1.13-1.34), Minority status and language (RR, 1.24; 95% CI, 1.03-1.48), housing and transportation (RR, 1.13; 95% CI, 1.02-1.26), and ICE (RR, 1.20; 95% CI, 1.11-1.30). Furthermore, top-quartile ICE was associated with greater risk for inappropriate follow-up among high-risk versus lower risk IPNs (RR, 1.33 [95% CI, 1.18-1.50] versus 1.13 [95% CI, 1.02-1.25]), respectively; P for interaction = .017). CONCLUSIONS: Local social vulnerability and residential segregation are associated with inappropriate IPN follow-up and may inform policy or interventions tailored for neighborhoods.

Controlled p-Type Doping of Pyrite FeS2.

Pyrite FeS2 has extraordinary potential as a low-cost, nontoxic, sustainable photovoltaic but has underperformed dramatically in prior solar cells. The latter devices focus on heterojunction designs, which are now understood to suffer from problems associated with FeS2 surfaces. Simpler homojunction cells thus become appealing but have not been fabricated due to the historical inability to understand and control doping in pyrite. While recent advances have put S-vacancy and Co-based n-doping of FeS2 on a firm footing, unequivocal evidence for bulk p-doping remains elusive. Here, we demonstrate the first unambiguous and controlled p-type transport in FeS2 single crystals doped with phosphorus (P) during chemical vapor transport growth. P doping is found to be possible up to at least ∼100 ppm, inducing ∼1018 holes/cm3 at 300 K, while leaving the crystal structure and quality unchanged. As the P doping is increased in crystals natively n-doped with S vacancies, the majority carrier type inverts from n to p near ∼25 and ∼55 ppm P, as detected by Seebeck and Hall effects, respectively. Detailed temperature- and P-doping-dependent transport measurements establish that the P acceptor level is 175 ± 10 meV above the valence band maximum, explain details of the carrier inversion, elucidate the relative mobility of electrons and holes, reveal mid-gap defect levels, and unambiguously establish that the inversion to p-type occurs in the bulk and is not an artifact of hopping conduction. Such controlled bulk p-doping opens the door to pyrite p-n homojunctions, unveiling new opportunities for solar cells based on this extraordinary semiconductor.

Reduction in Radiologist Interpretation Time of Serial CT and MR Imaging Findings with Deep Learning Identification of Relevant Priors, Series and Finding Locations.

RATIONALE AND OBJECTIVES: Finding comparison to relevant prior studies is a requisite component of the radiology workflow. The purpose of this study was to evaluate the impact of a deep learning tool simplifying this time-consuming task by automatically identifying and displaying the finding in relevant prior studies. MATERIALS AND METHODS: The algorithm pipeline used in this retrospective study, TimeLens (TL), is based on natural language processing and descriptor-based image-matching algorithms. The dataset used for testing comprised 3872 series of 246 radiology examinations from 75 patients (189 CTs, 95 MRIs). To ensure a comprehensive testing, five finding types frequently encountered in radiology practice were included: aortic aneurysm, intracranial aneurysm, kidney lesion, meningioma, and pulmonary nodule. After a standardized training session, nine radiologists from three university hospitals performed two reading sessions on a cloud-based evaluation platform resembling a standard RIS/PACS. The task was to measure the diameter of the finding-of-interest on two or more exams (a most recent and at least one prior exam): first without use of TL, and a second session at an interval of at least 21 days with the use of TL. All user actions were logged for each round, including time needed to measure the finding at all timepoints, number of mouse clicks, and mouse distance traveled. The effect of TL was evaluated in total, per finding type, per reader, per experience (resident vs. board-certified radiologist), and per modality. Mouse movement patterns were analyzed with heatmaps. To assess the effect of habituation to the cases, a third round of readings was performed without TL. RESULTS: Across scenarios, TL reduced the average time needed to assess a finding at all timepoints by 40.1% (107 vs. 65 seconds; p < 0.001). Largest accelerations were demonstrated for assessment of pulmonary nodules (-47.0%; p < 0.001). Less mouse clicks (-17.2%) were needed for finding evaluation with TL, and mouse distance traveled was reduced by 38.0%. Time needed to assess the findings increased from round 2 to round 3 (+27.6%; p < 0.001). Readers were able to measure a given finding in 94.4% of cases on the series initially proposed by TL as most relevant series for comparison. The heatmaps showed consistently simplified mouse movement patterns with TL. CONCLUSION: A deep learning tool significantly reduced both the amount of user interactions with the radiology image viewer and the time needed to assess findings of interest on cross-sectional imaging with relevant prior exams.

ACR Appropriateness Criteria® Routine Chest Imaging.

Routine chest imaging has been used to identify unknown or subclinical cardiothoracic abnormalities in the absence of symptoms. Various imaging modalities have been suggested for routine chest imaging. We review the evidence for or against the use of routine chest imaging in different clinical scenarios. This document aims to determine guidelines for the use of routine chest imaging as initial imaging for hospital admission, initial imaging prior to noncardiothoracic surgery, and surveillance imaging for chronic cardiopulmonary disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Reductive C-O Cleavage of Ethereal Solvents and 18-Crown-6 in Ln(NR2)3/KC8 Reactions (R = SiMe3).

The high reactivity accessible from the reduction of the tris(amide) complexes Ln(NR2)3 (R = SiMe3) with potassium graphite in the presence of a variety of ethers is demonstrated by crystal structures of six different types of products of C-O bond cleavage reactions with Ln = Y, Ho, Er, and Lu. Specifically, 1,2-dimethoxyethane (DME) can be cleaved in Ln(NR2)3/KC8 reactions as shown by three different types of crystals: [K (crypt)][(R2N)3Y(OCH2CH2OCH3)], 1-Y, [(R2N)2Y(µ-OCH2CH2OCH3-κO,κO')]2, 2-Y, and [K2(18-c-6)3]{[(R2N)3Lu]2[(µ-OCH2CH2O)]}, 3-Lu (18-c-6 = 18-crown-6; crypt = 2.2.2-cryptand). THF can be ring opened by the Y(NR2)3/KC8 reaction system, as shown by crystals of the butoxide, [K(crypt)][(R2N)3Y(OCH2CH2CH2CH3)], 4-Y. The cyclic ether, oxetane, OC3H6, ring opens in Ln(NR2)3/KC8 reactions to form crystals of the propoxide, [K(18-c-6)(OC3H6)][(R2N)3Ln(OCH2CH2CH3)], 5-Ln, for Ln = Ho and Er. In Et2O, the Y(NR2)3/KC8 reactions do not attack the solvent, but C-O cleavage of 18-c-6 is observed to form {[(R2N)2]Y[µ-η1:η1-O2(C10H20O4)K]}2, 6-Y. These Ln(NR2)3/KC8 C-O cleavage reactions are typically accompanied by C-H bond activation reactions, which form cyclometalates such as [K(crypt)]{(R2N)2Ln[N(SiMe3)(SiMe2CH2)-κC,κN]}, 7-Ln (Ln = Y, Ho, Er), and [K(18-c-6)]{(R2N)2Y[N(SiMe3)(SiMe2CH2)-κC,κN]}, 8-Y, which are common decomposition products of Ln(NR2)3 reactions. In addition, in this study, the hydride complex, [K(18-c-6)][(R2N)3YH], 9-Y, was isolated. NMR analysis indicates that the yttrium reactions form mixtures that consistently contain the yttrium cyclometalates 7-Y and 8-Y as major components. These results show the diversity of available reaction pathways for the Ln(NR2)3/KC8 system and highlight the inherent difficulties in isolating Ln(II) complexes containing the [Ln(NR2)3]1- anion.

OME-Zarr: a cloud-optimized bioimaging file format with international community support.

A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself -- OME-Zarr -- along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain -- the file format that underlies so many personal, institutional, and global data management and analysis tasks.