Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

Predictions of photophysical properties of phosphorescent platinum(II) complexes based on ensemble machine learning approach.

Cyclometalated Pt(II) complexes are popular phosphorescent emitters with color-tunable emissions. To render their practical applications as organic light-emitting diodes emitters, it is required to develop Pt(II) complexes with high radiative decay rate constant and photoluminescence (PL) quantum yield. Here, a general protocol is developed for accurate predictions of emission wavelength, radiative decay rate constant, and PL quantum yield based on the combination of first-principles quantum mechanical method, machine learning, and experimental calibration. A new dataset concerning phosphorescent Pt(II) emitters is constructed, with more than 200 samples collected from the literature. Features containing pertinent electronic properties of the complexes are chosen and ensemble learning models combined with stacking-based approaches exhibit the best performance, where the values of squared correlation coefficients are 0.96, 0.81, and 0.67 for the predictions of emission wavelength, PL quantum yield and radiative decay rate constant, respectively. The accuracy of the protocol is further confirmed using 24 recently reported Pt(II) complexes, which demonstrates its reliability for a broad palette of Pt(II) emitters.

Total-body dynamic PET/CT imaging reveals kinetic distribution of [13N]NH3 in normal organs.

PURPOSE: To systematically investigate kinetic metrics and metabolic trapping of [13N]NH3 in organs. METHODS: Eleven participants performed total-body [13N]NH3 dynamic positron emission tomography (PET). Regions of interest were drawn in organs to obtain time-to-activity curves (TACs), which were fitted with an irreversible two-tissue compartment model (2TC) to investigate constant rates K1, k2 and k3, and to calculate Ki. Additionally, one-tissue compartment model using full data (1TCfull) and the first four minutes of data (1TC4min) were fitted to TAC data. K1 and k2 were compared among different models to assess [13N]NH3 trapping in organs. RESULTS: Kinetic rates of [13N]NH3 varied significantly among organs. The mean K1 ranged from 0.049 mL/cm3/min in the muscle to 2.936 mL/cm3/min in the kidney. The k2 and k3 were lowest in the liver (0.001 min- 1) and in the pituitary (0.009 min- 1), while highest in the kidney (0.587 min- 1) and in the liver (0.800 min- 1), respectively. The Ki was largest in the myocardium (0.601 ± 0.259 mL/cm3/min) while smallest in the bone marrow (0.028 ± 0.022 mL/cm3/min). Three groups of organs with similar kinetic characteristics were revealed: (1) the thyroid, the lung, the spleen, the pancreas, and the kidney; (2) the liver and the muscle; and (3) the cortex, the white matter, the cerebellum, the pituitary, the parotid, the submandibular gland, the myocardium, the bone, and the bone marrow. Obvious k3 was identified in multiple organs, and significant changes of K1 in multiple organs and k2 in most organs were found between 2TC and 1TCfull, but both K1 and k2 were comparable between 2TC and 1TC4min. CONCLUSION: The kinetic rates of [13N]NH3 differed among organs with some have obvious 13N-anmmonia trapping. The normal distribution of kinetic metrics of 13N-anmmonia in organs can serve as a reference for its potential use in tumor imaging.

Construction of C-S and C-Se Bonds from Unstrained Ketone Precursors under Photoredox Catalysis.

A mild photoredox catalyzed construction of sulfides, disulfides, selenides, sulfoxides and sulfones from unstrained ketone precursors is introduced. Combination of this deacylative process with SN 2 or coupling reactions provides novel and convenient modular strategies toward unsymmetrical or symmetric disulfides. Reactivity studies favor a bromine radical that initiates a HAT (Hydrogen Atom Transfer) from the aminal intermediate resulting in expulsion of a C-centered radical that is intercepted to make C-S and C-Se bonds. Gram scale reactions, broad substrate scope and tolerance towards various functional groups render this method appealing for future applications in the synthesis of organosulfur and selenium complexes.

Surface Lattice Modulation through Chemical Delithiation toward a Stable Nickel-Rich Layered Oxide Cathode.

Nickel-rich layered oxides (NLOs) are considered as one of the most promising cathode materials for next-generation high-energy lithium-ion batteries (LIBs), yet their practical applications are currently challenged by the unsatisfactory cyclability and reliability owing to their inherent interfacial and structural instability. Herein, we demonstrate an approach to reverse the unstable nature of NLOs through surface solid reaction, by which the reconstructed surface lattice turns stable and robust against both side reactions and chemophysical breakdown, resulting in improved cycling performance. Specifically, conformal La(OH)3 nanoshells are built with their thicknesses controlled at nanometer accuracy, which act as a Li+ capturer and induce controlled reaction with the NLO surface lattices, thereby transforming the particle crust into an epitaxial layer with localized Ni/Li disordering, where lithium deficiency and nickel stabilization are both achieved by transforming oxidative Ni3+ into stable Ni2+. An optimized balance between surface stabilization and charge transfer is demonstrated by a representative NLO material, namely, LiNi0.83Co0.07Mn0.1O2, whose surface engineering leads to a highly improved capacity retention and excellent rate capability with a strong capability to inhibit the crack of NLO particles. Our study highlights the importance of surface chemistry in determining chemical and structural behaviors and paves a research avenue in controlling the surface lattice for the stabilization of NLOs toward reliable high-energy LIBs.

Newly identified lncRNA-45 promotes breast cancer metastasis through activating the mTOR signaling pathway.

BACKGROUND: Metastasis, a complex multi-stage process, is the primary cause of breast cancer-related death. Unfortunately, the molecular mechanisms underlying tumor metastasis have not been fully elucidated thus far. Long noncoding RNAs (lncRNAs) dictate the behaviours of tumor cells via multiple signaling pathways, resulting in tumor cell migration and invasion, as well as all stages of cancer progression. LncRNAs function as regulators in shaping cellular activities directly through influencing key genes involved in biological processes of the tumor, and representing promising novel targets in cancer diagnosis and therapy. We therefore sought to define the correlations between lncRNA expression and breast cancer metastasis, especially to investigate the functional pathway underlying lncRNA-mediated tumor invasion and metastasis process. RESULTS: In this study, we compared the lncRNA transcriptome profiles between primary breast cancer 4T1 cells and high metastatic 4T1-LG12 cells. We found that many differently expressed lncRNAs greatly correlated to the metastatic propensity of 4T1-LG12 cells, particularly lncRNA-45, a new lncRNA without functional annotations, which was found to be the most upregulated lncRNA transcribed by an internal region within the regulatory associated with protein of mechanistic target of rapamycin kinase (mTOR) complex 1 (Rptor) gene. LncRNA-45 was uncovered to be involved in the epithelial-to-mesenchymal transition process of breast cancer cells, as evidenced by the observation that lncRNA-45 knockdown significantly suppressed the invasive capability of parental 4T1-LG12 cells. Molecular mechanistic investigation showed that reduced activity of mTORC1-associated pathway led to a decrease of total ribosomal protein S6 kinase, polypeptide 1 (S6K1) content and enhancement of autophagy, consequently compromising the metastatic propensity in lncRNA-45 knockdown cells. CONCLUSIONS: Overall, our experiments uncovered that the newly identified lncRNA-45 played a regulatory role in breast cancer cell metastasis.

Respiratory-gated PET imaging with reduced acquisition time for suspect malignancies: the first experience in application of total-body PET/CT.

OBJECTIVES: This study aimed to investigate the performance of respiratory-gating imaging with reduced acquisition time using the total-body positron emission tomography/computed tomography (PET/CT) scanner. METHODS: Imaging data of 71 patients with suspect malignancies who underwent total-body 2-[18F]-fluoro-2-deoxy-D-glucose PET/CT for 15 min with respiration recorded were analyzed. For each examination, four reconstructions were performed: Ungated-15, using all coincidences; Ungated-5, using data of the first 5 min; Gated-15 using all coincidences but with respiratory gating; and Gated-6 using data of the first 6 min with respiratory gating. Lesions were quantified and image quality was evaluated; both were compared between the four image sets. RESULTS: A total of 390 lesions were found in the thorax and upper abdomen. Lesion detectability was significantly higher in gated-15 (97.2%) than in ungated-15 (93.6%, p = 0.001) and ungated-5 (92.3%, p = 0.001), but comparable to Gated-6 (95.9%, p = 0.993). A total of 131 lesions were selected for quantitative analyses. Lesions in Gated-15 presented significantly larger standardized uptake values, tumor-to-liver ratio, and tumor-to-blood ratio, but smaller metabolic tumor volume, compared to those in Ungated-15 and Ungated-5 (all p < 0.001). These differences were more obvious in small lesions and in lesions from sites other than mediastinum/retroperitoneum. However, these indices were not significantly different between Gated-15 and Gated-6. Higher, but acceptable, image noise was identified in gated images than in ungated images. CONCLUSIONS: Respiratory-gating imaging with reduced scanning time using the total-body PET/CT scanner is superior to ungated imaging and can be used in the clinic. KEY POINTS: • In PET imaging, respiratory gating can improve lesion presentation and detectability but requires longer imaging time. • This single-center study showed that the total-body PET scanner allows respiratory-gated imaging with reduced and clinically acceptable scanning time.

Dynamic perfusion SPECT for functional evaluation in symptomatic patients with myocardial bridging.

BACKGROUND: The aim of this study was to investigate the feasibility and diagnostic value of myocardial flow reserve (MFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) in the functional evaluation of myocardial bridge (MB). METHODS: From May 2017 to July 2021, patients with angiographically confirmed isolated MB on the left anterior descending artery (LAD) who underwent dynamic SPECT myocardial perfusion imaging were retrospectively included. The assessment of semiquantitative indices of myocardial perfusion (summed stress scores, SSS) and quantitative parameters (MFR) was performed. RESULTS: A total of 49 patients were enrolled. The mean age of the subjects was 61.0 ± 9.0 years. All of the patients were symptomatic, and 16 cases (32.7%) presented with typical angina. SPECT-derived MFR showed a borderline significantly negative correlation with SSS (r = 0.261, P = .070). There was a trend of higher prevalence of impaired myocardial perfusion defined as MFR < 2 than as SSS ≥ 4 (42.9% vs 26.5%; P = .090). CONCLUSION: Our data support that SPECT MFR may be a useful parameter for the functional assessment of MB. In patients with MB, the use of dynamic SPECT could be a potential method for hemodynamic assessment.

Base-promoted tandem synthesis of 2-azaaryl indoline.

A novel tandem method to synthesize 2-azaaryl indoline promoted by LiN(SiMe3)2 from 2-azaaryl methyl amine and 2-fluoro benzyl bromides was developed. Mechanistic investigation indicated that this tandem cyclization was initiated by selective benzyl C-SN2 substitution followed by an intramolecular SNAr reaction. Diverse 2-azaaryl indoles could also be obtained via simple functional transformations.

Alleviation of loperamide-induced constipation with sticky rice fermented huangjiu by the regulation of serum neurotransmitters and gut microbiota.

BACKGROUND: Huangjiu is an important component of traditional fermented food. It is produced by cereal fermentation. Sticky rice fermented huangjiu is an abundant source of polysaccharides, oligosaccharides, proteins, amino acids, and flavor compounds (POPAF), and it has been used as a dietary supplement and pharmaceutical ingredient. The purpose of this study is to explore the alleviation of constipation using sticky rice fermented huangjiu, with the aim of providing a basis for the nutritional treatment of constipation. RESULTS: Sticky rice fermented huangjiu was more effective in the alleviation of constipation than same concentration of ethanol treatment on serum neurotransmitters, gut microbiota, and intestinal metabolites in this 17 days constipation mouse model. Compared with ethanol treatment, the administration of sticky rice fermented huangjiu to constipated mice increased gastrointestinal motility. It alleviated the decrease in motilin (27.94%), substance P (13.85%), gastrin (63.46%), 5-hydroxytryptamine (4.55%), and short-chain fatty acid (19.80%) levels, and alleviated the increase in somatostatin levels (9.54%). Furthermore, the administration of sticky rice fermented huangjiu regulated the microbiota-mediated gut ecology through alterations in the characteristic taxa. CONCLUSION: The results reveal that sticky rice fermented huangjiu may alleviate loperamide-induced constipation by the regulation of serum neurotransmitters and gut microbiota. These findings reveal that huangjiu is endowed with many functional components by cereal fermentation, and the bioactive substances in huangjiu can be separated and applied for medical treatment or diet therapy in the future. © 2022 Society of Chemical Industry.

Investigating ultra-low-dose total-body [18F]-FDG PET/CT in colorectal cancer: initial experience.

PURPOSE: This study was to evaluate the effects of an ultra-low dose of [18F]-FDG on the image quality of total-body PET/CT and its lesion detectability in colorectal cancer (CRC). METHODS: Sixty-two CRC patients who underwent total-body PET/CT (uEXPLORER, United Imaging Healthcare, Shanghai, China) with an ultra-low dose (0.37 MBq/kg) of [18F]-FDG were enrolled in this retrospective study. The PET images were reconstructed with the entire 15-min dataset first and then split into 13-, 8-, 5-, 4-, 3-, 2-, and 1-min duration groups to simulate fast scanning images. For simplicity, the images reconstructed with the data from 15 to 1 min were referred to as G15, G13, and so on until G1. Subjective image quality was assessed with 5-point Likert scales. The objective image quality parameters included the SUVmax, SUVmean, and signal-to-noise ratio (SNR) of the liver and blood pool and the SUVmax and tumor-to-background ratio (TBR) of the lesions. G15 served as the control to evaluate lesion detectability. RESULTS: A total of 62 patients (43 men, 19 women; age 41-88, mean ± SD 64.0 ± 10.9 years) with 64 CRC primary tumor lesions and 10 low-grade intraepithelial neoplasia (LGIN) lesions were enrolled in this study. The subjective scores were highest for G15 (4.5 ± 0.5) and then decreased from G13 (4.3 ± 0.4) to G8 (3.7 ± 0.5). The liver SNR increased with the extension of acquisition time from G8 (17.2 ± 2.8) to G13 (20.6 ± 3.4) and G15 (21.9 ± 3.4). The liver SNR of G8 was not significantly different from that of G13 (p = 0.15) and was significantly different from that of G15 (p = 0.001). All 64 CRC lesions could be identified in all image groups, even on G1. One of ten LGINs was missed on G1, G2, and G3, and one LGIN was missed on G1, G2, G3, and G4. G15 served as the control, and 100% (48/48) lymph nodes could be found on G13 and G8 compared to 93.8% (45/48) lymph nodes on G5 and G4, 85.4% (41/48) lymph nodes on G3, 81.3% (39/48) lymph nodes on G2, and 77.1% (37/48) lymph nodes on G1. For liver metastases, there were no missed liver lesions on G13 and G8 and 3, 4, 6, 7, and 9 missed liver lesions on G5, G4, G3, G2, and G1, respectively. For other areas of metastasis, including the lung, peritoneum, and ovaries, there were no missed lesions in any group. CONCLUSIONS: Total-body PET/CT with an ultra-low dose of [18F]-FDG can maintain satisfactory image quality and lesion detectability in CRC.

Energy-resolved and time-dependent unimolecular dissociation of hydroperoxyalkyl radicals (˙QOOH).

Hydroperoxyalkyl radicals (˙QOOH) are transient intermediates in the atmospheric oxidation of volatile organic compounds and combustion of hydrocarbon fuels in low temperature (<1000 K) environments. The carbon-centered ˙QOOH radicals are a critical juncture in the oxidation mechanism, but have generally eluded direct experimental observation of their structure, stability, and dissociation dynamics. Recently, this laboratory demonstrated that a prototypical ˙QOOH radical [˙CH2(CH3)2COOH] can be synthesized by an alternative route, stabilized in a pulsed supersonic expansion, and characterized by its infrared (IR) spectroscopic signature and unimolecular dissociation rate to OH radical and cyclic ether products. The present study focuses on a partially deuterated ˙QOOD analog ˙CH2(CH3)2COOD, generated in the laboratory by H-atom abstraction from partially deuterated tert-butyl hydroperoxide, (CH3)3COOD. IR spectral features associated with jet-cooled and isolated ˙QOOD radicals are observed in the vicinity of the transition state (TS) barrier leading to OD radical and cyclic ether products. The overtone OD stretch (2νOD) of ˙QOOD is identified by IR action spectroscopy with UV laser-induced fluorescence detection of OD products. Direct time-domain measurement of the unimolecular dissociation rate for ˙QOOD (2νOD) extends prior rate measurements for ˙QOOH. Partial deuteration results in a small increase in the TS barrier predicted by high level electronic structure calculations due to changes in zero-point energies; the imaginary frequency is unchanged. Comparison of the unimolecular decay rates obtained experimentally with those predicted theoretically for both ˙QOOH and ˙QOOD confirm that unimolecular decay is enhanced by heavy-atom tunneling involving simultaneous O-O bond elongation and C-C-O angle contraction along the reaction pathway.

Carbonyl-Assisted Iridium-Catalyzed C-H Amination Using 2,2,2-Trichloroethoxycarbonyl Azide.

The carbonyl-directed, mono C-H amination of arenes has been achieved using [Cp*Ir(III)Cl2]2 as the catalyst and 2,2,2-trichloroethoxycarbonyl (Troc) azide as an aminating reagent. The amination proceeds smoothly with a variety of arylcarbonyl compounds, including alkyl and vinyl arylketones, secondary and tertiary aryl amides, and acetyl indoles. The resulting ortho-TrocNH arylcarbonyl compounds are easily transformed to the corresponding free arylamines, aryl carbamates, or aryl ureas. Taking advantage of the electrophilic nature of both Troc and carbonyl groups in ortho-TrocNH arylcarbonyl compounds, the subsequent cyclization with dinucleophilic reagents has also been demonstrated. This provides an efficient strategy for the construction of aryl-fused N-heterocycles.

Functional significance of intermediate coronary stenosis in patients with single-vessel coronary artery disease: A comparison of dynamic SPECT coronary flow reserve with intracoronary pressure-derived fractional flow reserve (FFR).

BACKGROUND: The aim of this study was to investigate the correlation of coronary flow reserve (CFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) with intracoronary pressure-derived fractional flow reserve (FFR) in patients with single-vessel coronary artery disease (CAD). METHODS: Patients with suspected or known stable CAD who were referred for invasive coronary angiography were prospectively enrolled. Both invasive FFR and SPECT were performed in subjects with single-vessel intermediate coronary stenosis. A cutoff value of < 0.8 was used to define abnormal FFR. RESULTS: A total of 34 patients were enrolled. The mean age of the subjects was 62.1 ± 6.7 years, and 79.4% were male. SPECT-derived CFR showed a significantly moderate correlation with FFR (r = 0.505, P = .003). The diagnostic performance for the identification of abnormal FFR in terms of sensitivity, specificity, and accuracy was 88.9%, 83.3%, and 87.9%, respectively, for CFR, with an optimized cutoff value of 1.73. CONCLUSION: In patients with single-vessel CAD, SPECT CFR was useful for the detection of functionally significant stenosis. Our data support the use of this technique as an optional method for hemodynamic assessment, especially when FFR results are in normal range.

Predicting Experimental Heats of Formation via Deep Learning with Limited Experimental Data.

When it comes to predicting experimental values of molecular properties with deep learning, the key problem is the lack of sufficient experimental data for training. We propose a method that consists of pretraining a graph neural network that aims to reproduce first-principles quantum mechanical results, followed by fine-tuning of a fully connected neural network against experimental results. The combined pretraining and fine-tuning model is expected to yield molecular properties close to experimental accuracy. This is made possible because first-principles quantum mechanical methods are often qualitatively correct or semiquantitatively accurate; thus, a calibration of the calculation results against high-precision but limited experiment data can improve accuracy greatly. Moreover, the method is highly efficient, as first-principles quantum mechanical calculation is bypassed. To demonstrate this, we apply the combined model to determine the experimental heats of formation of organic molecules made of H, C, O, N, or F atoms (up to 30 atoms), where mere 405 experimental data are used. The overall mean absolute error is 1.8 kcal/mol for these molecules.

NEMA NU2-2012 performance measurements of the United Imaging uPMR790: an integrated PET/MR system.

PURPOSE: In this paper, we aimed to evaluate the positron emission tomography (PET) performance of, to the best of our knowledge, the third commercially available whole-body integrated PET/magnetic resonance (MR) system. METHODS: The PET system performance was measured following the NEMA standards with and without simultaneous MR operation. PET spatial resolution, sensitivity, scatter fraction, count-rate performance, accuracy of count losses and random corrections, image quality, and time-of-flight (TOF) resolution were quantitatively evaluated. Clinical scans were acquired at the PET/MR system and compared with images acquired at a PET/CT with the same digital detector technology. RESULTS: Measurement results of essential PET performance were reported in the form of MR idle (MR pulsing). The axial, radial, and tangential spatial resolutions were measured as 2.72 mm (2.73 mm), 2.86 mm (2.85 mm), and 2.81 mm (2.82 mm) FWHM, respectively, at 1 cm radial offset. The NECR peak was measured as 129.2 kcps (129.5 kcps) at 14.7 kBq mL-1 (14.2 kBq mL-1). The scatter fraction at NECR peak was 37.9% (36.5%), and the maximum slice error below NECR was 4.1% (4.5%). Contrast recovery coefficients ranged from 51.8% (52.3%) for 10 mm hot sphere to 87.3% (87.2%) for 37 mm cold sphere. TOF resolution at 5.3 kBq mL-1 was measured at 535 ps (540 ps). With point source, TOF was measured to be 474 ps (485 ps). Clinical scans revealed similar image quality from the PET/MR and the comparative PET/CT system. CONCLUSION: The PET performance of the newly introduced integrated PET/MR system is not significantly affected by the simultaneous operation of an MR sequence (2-point DIXON sequence). Measurement results demonstrate comparable performance with other state-of-the-art PET/MR systems. The clinical benefits of high spatial resolution and long axial coverage remain to be further evaluated in specific clinical imaging applications.

Total-body 18F-FDG PET/CT scan in oncology patients: how fast could it be?

PURPOSE: The aim of the study was to determine a faster PET acquisition protocol for a total-body PET/CT scanner by assessing the image quality that is equivalent to a conventional digital PET/CT scanner from both a phantom and a clinical perspective. METHODS: A phantom study using a NEMA/IEC NU-2 body phantom was first performed in both a total-body PET/CT (uEXPLORER) and a routine digital PET/CT (uMI 780), with a hot sphere to background activity concentration ratio of 4:1. The contrast recovery coefficient (CRC), background variability (BV), and recovery coefficient (RC: RCmax and RCmean) were assessed in the uEXPLORER with different scanning durations and reconstruction protocols, which were compared to those acquired from the uMI 780 with clinical acquisition settings. The coefficient of variation (COV) of the uMI 780 with clinical settings was calculated and used as a threshold reference to determine the optimized scanning duration and reconstruction protocol for the uEXPLORER. The obtained protocol from the phantom study was subsequently tested and validated in 30 oncology patients. Images acquired from the uMI 780 with 2-3 min per bed position were referred as G780 and served as the reference for comparison. All PET raw data from the uEXPLORER were reconstructed using the data-cutting technique to simulate a 30-s, 45-s, or 60-s acquisition duration, respectively. The iterations were 2 and 3 for the uEXPLORER, referred as G30s_3i, G45s_2i, G45s_3i, G60s_2i, and G60s_3i, respectively. A 5-point Likert scale was used in the qualitative analysis to assess the image quality. The image quality was also evaluated by the liver COV, the lesion target-to-background ratio (TBR), and the lesion signal-to-noise ratio (SNR). RESULTS: In the phantom study, CRC, BV, RCmax, and RCmean in the uEXPLORER with different scanning durations and reconstruction iterations were compared with those in the uMI 780 with clinical settings. A minor fluctuation was found among different scanning durations. COV of the uMI 780 with clinical settings was 11.6%, and a protocol with a 30-45-s scanning duration and 2 or 3 iterations for the uEXPLORER was found to provide an equivalent image quality as the uMI 780. An almost perfect agreement was shown with a kappa value of 0.875. The qualitative score of the G30s_3i in the uEXPLORER was inferior to the G780 reference (p = 0.001); however, the scores of other groups in the uEXPLORER with a 45-s and above acquisition time were higher than the G780 in the uMI 780. In quantitative analysis, the delay time between the two scans in the two orders was not significantly different. There was no significant difference of the liver COV between the G780 and G30s_3i (p = 0.162). A total of 33 lesions were analyzed in the clinical patient study. There was no significant difference in lesion TBR between the reference G780 and the G45s_2i obtained from the uEXPLORER (p = 0.072), while the latter showed a higher lesion SNR value compared to that in uMI 780 with clinical settings (p < 0.001). CONCLUSIONS: This study showed that a fast PET protocol with a 30-45-s acquisition time in the total-body uEXPLORER PET/CT can provide an equivalent image quality as the conventional digital uMI 780 PET/CT with longer clinical acquisition settings.

Total-body PET/CT using half-dose FDG and compared with conventional PET/CT using full-dose FDG in lung cancer.

PURPOSE: The purpose was to explore the effects of total-body PET/CT with half-dose 18F-FDG activity on image quality, compared with those of conventional PET/CT with clinical routine full-dose 18F-FDG in lung cancer. METHODS: Fifty-six primary lung cancer patients who underwent total-body PET/CT on a uEXPLORER scanner with half-dose (1.85 MBq/kg) 18F-FDG activity before treatment were retrospectively studied; among them, 28 patients were confirmed by postoperative pathologic examination and 28 patients by biopsy. After matching with the pathological study results, the other 28 patients with lung cancer who underwent surgery were selected for the full-dose (3.70 MBq/kg) group. Patients in the full-dose group were studied with a conventional uM780 PET/CT scanner. The acquisition time of the half-dose group was 15 min, split into 4-min and 2-min duration groups, which were all referred to as G15, G4 and G2, respectively. The PET/CT scanning speed in the full-dose group was 2 min/bed. Image quality was evaluated by subjective and objective analyses. The subjective analysis method was carried out with a 5-point scale (5-excellent, 1-poor). Objective analysis indicators of PET image quality included the SUVmax, SUVmean and signal-to-noise ratio (SNR) of the liver; the SUVmax and SUVmean of the blood pool; and the SUVmax and tumour-to-background ratio (TBR) of the lesions. G15 served as the reference for G2 and G4 to test lesion detectability. RESULTS: Image quality scores in G2 (4.3 ± 0.7) were significantly higher than those in the full-dose group (3.7 ± 0.6) (p = 0.004). The mean and SD of the image quality scores in G4 and G15 were 4.9 ± 0.2 and 5.0 ± 0.0, respectively. The liver SNR in G2 was significantly higher than that in the full-dose group; the corresponding SNR were 11.7 ± 1.5 and 8.3 ± 1.2 (p < 0.001), respectively. The liver SNR significantly increased with the time of acquisition among G2, G4 and G15 (11.1 ± 1.7, 15.2 ± 3.4 and 30.5 ± 6.0, all p < 0.05). G15 served as the reference, and all these lesions (100%) could be identified by G2 and G4. CONCLUSION: Total-body PET/CT with half-dose 18F-FDG activity in G2 and G4 achieved comparable image quality to conventional PET/CT, and its image quality was better than that of conventional PET/CT with clinical routine full-dose 18F-FDG in lung cancer.

Are prenatal anxiety or depression symptoms associated with asthma or atopic diseases throughout the offspring's childhood? An updated systematic review and meta-analysis.

BACKGROUND: Asthma is the most common respiratory disease among children, while atopic diseases such as atopic dermatitis affect about 20% of infants under 2 years of age. Studies suggested that these conditions might be related to prenatal depression or anxiety. This study aimed to explore the association between prenatal mental disorders and childhood asthma or atopic disease in a systematic review and meta-analysis. METHODS: PubMed, Embase, and the Cochrane Library were searched up to May 2020. The primary outcome was childhood asthma and childhood atopic dermatitis. Random-effects models were used because of high heterogeneity indicated by I2 > 50% and Q-test P < 0.10. RESULTS: A total of 598 studies were initially identified, but nine studies met the inclusion criteria. Prenatal mental disorder was associated with childhood asthma (n = 6 studies; ES = 1.146, 95%CI: 1.054-1.245, P = 0.001; I2 = 93.5%, Pheterogeneity < 0.001) whereas no significant association was found for childhood atopic dermatitis (n = 4 studies; ES = 1.211, 95%CI: 0.982-1.494, P = 0.073; I2 = 78.5%, Pheterogeneity < 0.001). Childhood asthma seems to be related more to depression (n = 1 study; ES = 1.170, 95%CI: 1.061-1.291, P = 0.002) and anxiety/depression (n = 4 studies; ES = 1.157, 95%CI: 1.050-1.275, P = 0.073; I2 = 95.3%, Pheterogeneity < 0.001). CONCLUSION: This meta-analysis demonstrated that prenatal mental disorders increase the risk of childhood asthma. We limited the included samples to pregnant women to investigate the association between prenatal psychological factors and offspring's physical health. Future studies should include large high-quality cohort studies to investigate the behavioral, environmental, and genetic causes for this association.

Analysis of the long-term efficacy and safety of subcutaneous immunotherapy for atopic dermatitis.

Introduction: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by severe pruritus and eczematous skin lesions. Subcutaneous immunotherapy (SCIT) refers to repeated contact with gradually increasing doses of allergen extracts, which improve patient tolerance to such allergens and controls, or reduces allergic symptoms. This study aimed to explore the long-term efficacy and safety of SCIT for patients with AD sensitized to house-dust mite (HDM). Methods: We conducted a retrospective analysis of 378 patients with HDM-sensitized AD. Among these patients, 164 received SCIT plus pharmacotherapy for 3 years (SCIT group) and the other 214 patients received only pharmacotherapy (non-SCIT group). The scoring atopic dermatitis (SCORAD) and pruritus visual analog scale (VAS) scores, laboratory test results, and adverse effects were recorded. Results: The SCORAD and pruritus VAS scores significantly decreased in the SCIT group. Also, the SCIT group showed higher reduction ratios of SCORAD and pruritus VAS scores than those observed in the non-SCIT group at 3 years after treatment initiation. The risk of development of new sensitization was higher in the non-SCIT group than in the SCIT group (relative risk 1.92 [95% confidence interval {CI}, 1.30-2.85]; p < 0.05). The eosinophil count of the participants significantly differed in the complete response (CR) group (p < 0.05) but not in the non-CR group (p = 0.098). However, the serum total immunoglobulin E value was not significantly reduced (p = 0.204). Of 8421 injections given to the patients, 231 injections (2.74%) showed adverse effects during the treatment period. Conclusion: Three years of SCIT can significantly reduce the severity and pruritus of moderate-to-severe AD with HDM sensitization. Patients who are multisensitized can also benefit from HDM SCIT. Patients can achieve long-term effects, such as prevention of neoallergen sensitization and inhibition of the allergy march.