A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

Diverse polarization angle swings from a repeating fast radio burst source.

Fast radio bursts (FRBs) are millisecond-duration radio transients1,2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3-5 or relativistic shocks far from the central energy source6-8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10 or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.

Molecular characterization of clinically isolated Pseudomonas aeruginosa with varying resistance to ceftazidime-avibactam and ceftolozane-tazobactam collected as a part of the ATLAS global surveillance program from 2020 to 2021.

Ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) are important agents for treating multidrug-resistant P. aeruginosa infections. In this study, we evaluated the molecular characteristics of 300 globally collected clinical P. aeruginosa isolates non-susceptible (NS) to CZA, C/T, or both agents. Isolates were CZA-NS and C/T-NS (n = 57), CZA-susceptible (S) and C/T-NS (n = 145), or CZA-NS and C/T-S (n = 98) selected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) surveillance program from 2020 to 2021. Characterization was by whole-genome sequencing. Analysis was performed to identify ß-lactamase genes and mutations that impact efflux regulation, AmpC regulation, and target binding (PBP3). Of the 57 CZA-NS+C/T-NS isolates, 64.9% carried a metallo-ß-lactamase (MBL), and a cumulative 84.2% carried any non-intrinsic ß-lactamase [i.e., not Pseudomonas-derived cephalosporinase (PDC) or OXA-50-like]. Of the 145 CZA-S+C/T-NS isolates, 26.2% carried an extended-spectrum ß-lactamase (ESBL) and no carbapenemase, 17.9% carried a serine-carbapenemase, and 42.1% were negative for non-intrinsic ß-lactamases. Of 98 CZA-NS+C/T-S isolates, 34.7% carried mutations previously described as causing an upregulation of the MexAB-OprM efflux pump, while only 9.2% carried a non-intrinsic ß-lactamase, and no resistance mechanism was identified in 29.6% of these isolates. MBLs were present in most isolates NS to both agents. More than half of the CZA-S+C/T-NS isolates carried serine ß-lactamases. The most frequently identified resistance mechanism identified in CZA-NS+C/T-S isolates was a marker indicating the upregulation of MexAB-OprM. No mechanism was identified that is thought to support resistance to these agents in numerous isolates. This may be due in part to the fact that whole genome sequencing (WGS) cannot directly measure gene expression of chromosomal resistance mechanisms.

An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial.

BACKGROUND: Guidelines recommend effective on-demand therapy for all individuals with hereditary angioedema. We aimed to assess the novel oral plasma kallikrein inhibitor, sebetralstat, which is in development, for on-demand treatment of hereditary angioedema attacks. METHODS: In this two-part phase 2 trial, individuals with type 1 or 2 hereditary angioedema aged 18 years or older were recruited from 25 sites, consisting of specialty outpatient centres, across nine countries in Europe and the USA. Individuals were eligible if they had experienced at least three hereditary angioedema attacks in the past 93 days, were not on prophylactic therapy, and had access to and the ability to self-administer conventional attack treatment. In part 1 of the trial, participants were given a single 600 mg open-label oral dose of sebetralstat to assess safety, pharmacokinetics, and pharmacodynamics of the dose. Part 2 was a randomised, double-blind, placebo-controlled, two-sequence, two-period (2 × 2) crossover trial; participants were randomly assigned (1:1) to either sequence 1, in which they were given a single dose of 600 mg of sebetralstat to treat the first eligible attack and a second dose of placebo to treat the second eligible attack, or sequence 2, in which they were given placebo to treat the first eligible attack and then 600 mg of sebetralstat to treat the second eligible attack. Participants and investigators were masked to treatment assignment. The primary endpoint was time to use of conventional attack treatment within 12 h of study drug administration, which was assessed in all participants who were randomly assigned to treatment and who received study drug for two attacks during part 2 of the study. Safety was assessed in all participants who received at least one dose of study drug, starting in part 1. This study is registered with ClinicalTrials.gov, NCT04208412, and is completed. FINDINGS: Between July 2, 2019, and Dec 8, 2020, 84 individuals were screened and 68 were enrolled in part 1 and received sebetralstat (mean age 38·3 years [SD 13·2], 37 [54%] were female, 31 [46%] were male, 68 [100%] were White). 42 (62%) of 68 participants completed pharmacokinetic assessments. Sebetralstat was rapidly absorbed, with a geometric mean plasma concentration of 501 ng/mL at 15 min. In a subset of participants (n=6), plasma samples obtained from 15 min to 4 h after study drug administration had near-complete protection from ex vivo stimulated generation of plasma kallikrein and cleavage of high-molecular-weight kininogen. In part 2, all 68 participants were randomly assigned to sequence 1 (n=34) or sequence 2 (n=34). 53 (78%) of 68 participants treated two attacks (25 [74%] in the sequence 1 group and 28 [82%] in the sequence 2 group). Time to use of conventional treatment within 12 h of study drug administration was significantly longer with sebetralstat versus placebo (at quartile 1: >12 h [95% CI 9·6 to >12] vs 8·0 h [3·8 to >12]; p=0·0010). There were no serious adverse events or adverse event-related discontinuations. INTERPRETATION: Oral administration of sebetralstat was well tolerated and led to rapid suppression of plasma kallikrein activity, resulting in increased time to use of conventional attack treatment and faster symptom relief versus placebo. Based on these results, a phase 3 trial to evaluate the efficacy and safety of two dose levels of sebetralstat in adolescent and adult participants with hereditary angioedema has been initiated (NCT05259917). FUNDING: KalVista Pharmaceuticals.

Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Hereditary angioedema is a rare and potentially life-threatening genetic disease that is associated with kallikrein-kinin system dysregulation. Garadacimab (CSL312), a novel, fully-human monoclonal antibody that inhibits activated factor XII (FXIIa), is being studied for the prevention of hereditary angioedema attacks. The aim of this study was to evaluate the efficacy and safety of once-monthly subcutaneous administrations of garadacimab as prophylaxis for hereditary angioedema. METHODS: VANGUARD was a pivotal, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial that recruited patients (aged ≥12 years) with type I or type II hereditary angioedema across seven countries (Canada, Germany, Hungary, Israel, Japan, the Netherlands, and the USA). Eligible patients were randomly assigned (3:2) to receive garadacimab or placebo for 6 months (182 days) by an interactive response technology (IRT) system. Randomisation was stratified by age (≤17 years vs >17 years) and baseline attack rate (1 to <3 attacks per month vs ≥3 attacks per month) for the adult group. The randomisation list and code were kept by the IRT provider during the study, with no access by site staff and funding representatives. All patients and investigational site staff, and representatives from the funder (or their delegates) with direct interaction with the study sites or patients, were masked to treatment assignment in a double-blind fashion. Randomly assigned patients received a 400-mg loading dose of subcutaneous garadacimab as two 200-mg injections or volume-matched placebo on day 1 of the treatment period, followed by five additional self-administered (or caregiver-administered) monthly doses of 200-mg subcutaneous garadacimab or volume-matched placebo. The primary endpoint was the investigator-assessed time-normalised number of hereditary angioedema attacks (number of hereditary angioedema attacks per month) during the 6-month treatment period (day 1 to day 182). Safety was evaluated in patients who received at least one dose of garadacimab or placebo. The study is registered with the EU Clinical Trials Register, 2020-000570-25 and ClinicalTrials.gov, NCT04656418. FINDINGS: Between Jan 27, 2021, and June 7, 2022, we screened 80 patients, 76 of whom were eligible to enter the run-in period of the study. Of 65 eligible patients with type I or type II hereditary angioedema, 39 were randomly assigned to garadacimab and 26 to placebo. One patient was randomly assigned in error and did not enter the treatment period (no dose of study drug received), resulting in 39 patients assigned to garadacimab and 25 patients assigned to placebo being included. 38 (59%) of 64 participants were female and 26 (41%) were male. 55 (86%) of 64 participants were White, six (9%) were Asian (Japanese), one (2%) was Black or African American, one (2%) was Native Hawaiian or Other Pacific Islander, and one (2%) was listed as other. During the 6-month treatment period (day 1 to day 182), the mean number of investigator-confirmed hereditary angioedema attacks per month was significantly lower in the garadacimab group (0·27, 95% CI 0·05 to 0·49) than in the placebo group (2·01, 1·44 to 2·57; p<0·0001), corresponding to a percentage difference in means of -87% (95% CI -96 to -58; p<0·0001). The median number of hereditary angioedema attacks per month was 0 (IQR 0·00-0·31) for garadacimab and 1·35 (1·00-3·20) for placebo. The most common treatment-emergent adverse events were upper-respiratory tract infections, nasopharyngitis, and headaches. FXIIa inhibition was not associated with an increased risk of bleeding or thromboembolic events. INTERPRETATION: Monthly garadacimab administration significantly reduced hereditary angioedema attacks in patients aged 12 years and older compared with placebo and had a favourable safety profile. Our results support the use of garadacimab as a potential prophylactic therapy for the treatment of hereditary angioedema in adolescents and adults. FUNDING: CSL Behring.

IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer.

BACKGROUND: Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. PATIENTS AND METHODS: IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell ≥1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. RESULTS: Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P = 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy exposure. CONCLUSIONS: OS, which is dismal in patients with TNBC relapsing within <12 months, was not improved by adding atezolizumab to chemotherapy. A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials.

Screening of Polar Electron-Phonon Interactions near the Surface of the Rashba Semiconductor BiTeCl.

Understanding electron-phonon coupling in noncentrosymmetric materials is critical for controlling the internal fields which give rise to Rashba interactions. We apply time- and angle-resolved photoemission spectroscopy (trARPES) to study coherent phonons in the surface and bulk regions of the polar semiconductor BiTeCl. Aided by ab initio calculations, our measurements reveal the coupling of out-of-plane A_{1} modes and an in-plane E_{2} mode. By considering how these modes modulate the electric dipole moment in each unit cell, we show that the polar A_{1} modes are more effectively screened in the metallic surface region, while the nonpolar E_{2} mode couples in both regions. In addition to informing strategies to optically manipulate Rashba interactions, this Letter has broader implications for the behavior of electron-phonon coupling in systems characterized by inhomogeneous dielectric environments.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Prediction by uterine artery Doppler screening of small-for-gestational-age neonates at 19-24 weeks' gestation.

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Molecular rectification induced by magnetization alignment in organic-ferromagnetic devices.

Spin-dependent transport in ferromagnet/organic-ferromagnet/ferromagnet junctions is investigated theoretically under different alignment of magnetization orientations. The results demonstrate a significant current rectification at low bias voltages, and the rectifying direction relies on the relative magnetization orientation in each component. The orbital analysis demonstrates two underlying mechanisms for the rectification, the slight structural asymmetry of the molecule from spin radicals and distinct spin match between conducting electrons and the magnetic molecule upon the reversal of bias. The latter is responsible for the strong low-bias rectification and relies on the magnetization alignment. The effects of parameter strength, temperature and size on the rectification are discussed. This work explores a new route to achieve high-performance molecular rectifiers operating at low bias with controlled rectifying direction.

Deep learning-based computer-aided detection of ultrasound in breast cancer diagnosis: A systematic review and meta-analysis.

PURPOSE: The aim of this meta-analysis was to assess the diagnostic performance of deep learning (DL) and ultrasound in breast cancer diagnosis. Additionally, we categorized the included studies into two subgroups: B-mode ultrasound diagnostic subgroup and multimodal ultrasound diagnostic subgroup, and compared the performance differences of DL algorithms in breast cancer diagnosis using only B-mode ultrasound or multimodal ultrasound. METHODS: We conducted a comprehensive search for relevant studies published from January 01, 2017 to July 31, 2023 in the MEDLINE and EMBASE databases. The quality of the included studies was evaluated using the QUADAS-2 tool and radiomics quality scores (RQS). Meta-analysis was performed using R software. Inter-study heterogeneity was assessed by I^2 values and Q-test P-values, with sources of heterogeneity analyzed through a random effects model based on test results. Summary receiver operating characteristics (SROC) curves were used for meta-analysis across multiple trials, while combined sensitivity, specificity, and AUC were calculated to quantify prediction accuracy. Subgroup analysis and sensitivity analyses were also conducted to identify potential sources of study heterogeneity. Publication bias was assessed using the funnel plot method. (PROSPERO identifier: CRD42024545758). RESULTS: The 20 studies included a total of 14,955 cases, with 4197 cases used for model testing. Among these cases were 1582 breast cancer patients and 2615 benign or other breast lesions. The combined sensitivity, specificity, and AUC values across all studies were found to be 0.93, 0.90, and 0.732, respectively. In subgroup analysis, the multimodal subgroup demonstrated superior performance with combined sensitivity, specificity, and AUC values of 0.93, 0.88, and 0.787, respectively; whereas the combined sensitivity, specificity, and AUC value for the model B subgroup was at a level of 0.92, 0.91, and 0.642, respectively. CONCLUSIONS: The integration of DL with ultrasound demonstrates high accuracy in the adjunctive diagnosis of breast cancer, while the fusion of DL and multimodal breast ultrasound exhibits superior diagnostic efficacy compared to B-mode ultrasound alone.

Dual-energy CT-based radiomics for predicting pathological grading of invasive lung adenocarcinoma.

AIMS: The purpose of the study was to build a radiomics model using Dual-energy CT (DECT) to predict pathological grading of invasive lung adenocarcinoma. MATERIALS AND METHODS: The retrospective study enrolled 107 patients (80 low-grade and 27 high-grade) with invasive lung adenocarcinoma before surgery. Clinical features, radiographic characteristics, and quantitative parameters were measured. Virtual monoenergetic images at 50kev and 150kev were reconstructed for extracting DECT radiomics features. To select features for constructing models, Pearson's correlation analysis, intraclass correlation coefficients, and least absolute shrinkage and selection operator penalized logistic regression were performed. Four models, including the DECT radiomics model, the clinical-DECT model, the conventional CT radiomics model, and the mixed model, were established. Area under the curve (AUC) and decision curve analysis were used to measure the performance and the clinical value of the models. RESULTS: The radiomics model based on DECT exhibited outstanding performance in predicting tumor differentiation, with an AUC of 0.997 and 0.743 in the training and testing sets, respectively. Incorporating tumor density, lobulation, and effective atomic number at AP, the clinical-DECT model showed a comparable performance with an AUC of 0.836 in both the training and testing sets. In comparison to the conventional CT radiomics model (AUC of 0.998 in the training and 0.529 in the testing set) and the mixed model (AUC of 0.988 in the training and 0.707 in the testing set), the DECT radiomics model demonstrated a greater AUC value and provided patients with a more significant net benefit in the testing set. CONCLUSIONS: In contrast to the conventional CT radiomics model, the DECT radiomics model produced greater predictive performance in pathological grading of invasive lung adenocarcinoma.

MRI-based radiomics model to preoperatively predict mesenchymal transition subtype in high-grade serous ovarian cancer.

AIM: To develop a magnetic resonance imaging (MRI)-based radiomics model for the preoperative identification of mesenchymal transition (MT) subtype in high-grade serous ovarian cancer (HGSOC). MATERIALS AND METHODS: One hundred and eighty-nine patients with histopathologically confirmed HGSOC were enrolled retrospectively. Among the included patients, 55 patients were determined as the MT subtype and the remaining 134 were non-MT subtype. After extracting a total of 204 features from T2-weighted imaging (T2WI) and contrast-enhanced (CE)-T1WI images, the Mann-Whitney U-test, Spearman correlation test, and Boruta algorithm were adopted to select the optimal feature set. Three classifiers, including logistic regression (LR), support vector machine (SVM), and random forest (RF), were trained to develop radiomics models. The performance of established models was evaluated from three aspects: discrimination, calibration, and clinical utility. RESULTS: Seven radiomics features relevant to MT subtypes were selected to build the radiomics models. The model based on the RF algorithm showed the best performance in predicting MT subtype, with areas under the curves (AUCs) of 0.866 (95 % confidence interval [CI]: 0.797-0.936) and 0.852 (95 % CI: 0.736-0.967) in the training and testing cohorts, respectively. The calibration curves, supported with Brier scores, indicated very good consistency between observation and prediction. Decision curve analysis (DCA) showed that the RF-based model could provide more net benefit, which suggested favorable utility in clinical application. CONCLUSION: The RF-based radiomics model provided accurate identification of MT from the non-MT subtype and may help facilitate personalised management of HGSOC.

Double low-dose computed tomography (CT) angiography of craniocervical arteries using a test bolus of diluted contrast medium and a personalized contrast protocol.

AIM: To prospectively assess the value of a test bolus of diluted contrast medium (CM) combined with a personalized contrast protocol in craniocervical computed tomography angiography (cc-CTA) with low radiation and CM doses. MATERIALS AND METHODS: Eighty-six consecutive subjects were divided into two groups at random (43 in each one): group A: 100/Sn140 kVp, filtered back-projection reconstruction, iopromide (370 mgI/ml) 50 ml; group B: 80/Sn140 kVp, iterative reconstruction, iodixanol (270 mgI/ml). In group B, the test bolus contained 27 ml of diluted CM, a personalized protocol with low-concentration CM was used for angiography, and the test bolus injection duration in angiography remained the same. Artery values over 200 Hounsfield units were considered significant. RESULTS: Image quality for all cases was found to be diagnostic. No significant differences were found in the arterial densities of the ascending aorta or basilar artery between the groups. The values of the common carotid artery, internal carotid artery, and middle cerebral artery in group B were significantly lower. The effective dose and average iodine uptake were significantly lower in group B. CONCLUSION: With double-low-dose cc-CTA, test bolus scanning based on diluted CM combined with a personalized contrast protocol can yield diagnostic-quality images and significantly reduce the radiation and CM doses.

Comparative analysis of three-dimensional and two-dimensional models for predicting the malignancy probability of subsolid nodules.

AIM: To construct three-dimensional (3D) and two-dimensional (2D) models to predict the malignancy probability of subsolid nodules (SSNs) and compare their effectiveness. MATERIALS AND METHODS: A total of 371 SSNs from 332 patients, collected between January 2020 and January 2024, were included in the study. The SSNs were divided into a training set for constructing the models and a test set for validating the models. Models were developed using binary logistic backward regression, based on factors that showed significant differences in univariate analyses. The performance of the models was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC). The AUCs of different models were compared using the DeLong test. RESULTS: The AUCs for the two 3D models, one 2D model, and the Brock model were 0.785 (0.733-0.836), 0.776 (0.723-0.829), 0.764 (0.710-0.818), and 0.738 (0.679-0.798) in the training set. In the test set, these AUCs were 0.817 (0.706-0.928), 0.796 (0.679-0.913), 0.771 (0.647-0.895), and 0.790 (0.678-0.903). The two 3D models demonstrated statistically significant differences from the Brock model in the training set (P=0.024 and P=0.046). None of the four models showed significant differences in the test set (all P>0.05). CONCLUSION: The 3D models outperform both the 2D model and the Brock model in predicting the malignancy probability of SSNs, and the 3D model incorporating volume, mean CT attenuation value, and lobulation as factors performed the best.

Correlation study between bone metabolic markers, bone mineral density, and sarcopenia.

OBJECTIVE: To investigate the correlation between bone metabolism markers, bone mineral density (BMD), and sarcopenia. METHODS: A total of 331 consecutive patients aged ≥ 60 years who were hospitalized between November 2020 and December 2021 were enrolled. Participants were divided into sarcopenia and non-sarcopenia groups according to the Asian Working Group on Sarcopenia criteria (AWGS, 2019). The clinical data, bone metabolism markers (ß-CTX, N-MID, and TP1NP), and BMD were compared between the two groups. RESULTS: Age, ß-CTX, and N-MID of the sarcopenia group were higher than those of the non-sarcopenia group (P < 0.05), but the BMD T values were lower than those of the non-sarcopenia group (P < 0.05). Binary logistic regression analysis showed that increased femoral neck BMD (FNBMD) was a protective factor for sarcopenia, while increased ß-CTX was a risk factor. Pearson/Spearman correlation analysis showed that the diagnostic indices of sarcopenia were positively correlated with FNBMD and negatively correlated with ß-CTX and N-MID. Multiple linear regression analysis revealed that BMI and FNBMD significantly positively affected muscle strength and appendicular skeletal muscle mass (ASM). The FNBMD significantly positively affected physical performance, while ß-CTX significantly negatively affected muscle strength, ASM, and physical performance. CONCLUSION: Increased FNBMD may be a protective factor against sarcopenia, and increased ß-CTX may be a risk factor. The FNBMD significantly positively affected the diagnostic indices of sarcopenia, while ß-CTX significantly negatively affected them. BMD and bone metabolism marker levels may be considered in early screening for sarcopenia.

Development of a diagnostic model for pre-washout screening of primary aldosteronism.

PURPOSE: Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. METHODS: We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. RESULTS: PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. CONCLUSION: PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

Burden of lung cancer attributed to particulate matter pollution in China: an epidemiological study from 1990 to 2019.

OBJECTIVES: The aim of this study was to examine the disease burden of lung cancer attributable to particulate matter (PM2.5) pollution in China from 1990 to 2019. STUDY DESIGN: Data from the Global Burden of Disease Study 2019 were used to estimate the disease burden of tracheal, bronchus and lung cancer attributed to PM2.5 over time in China. METHODS: Joinpoint regression models were applied to disability-adjusted life years (DALYs) to assess the time trends and estimate the impact of PM2.5 on the overall disease burden of lung cancer. Furthermore, age-period-cohort models were conducted to assess the relationships between lung cancer DALYs attributed to PM2.5 exposure and age, calendar period and birth cohort trends in China from 1990 to 2019. RESULTS: Lung cancer DALYs attributable to household air pollution from solid fuels decreased with an average annual percent change (AAPC) of 2.9 % per 100,000 population, while those attributable to ambient particular matter pollution (APE) increased (AAPC: -4.7 % per 100,000 population) over the past 30 years. The burden of lung cancer in terms of DALYs in males was higher than in females, and it demonstrated an age-dependent increase. The period and cohort effects also had significant impacts on the DALYs rates of lung cancer attributable to APE, indicating an overall increase in lung cancer DALYs for all age groups in each year. CONCLUSIONS: This study highlights the need for effective strategies to reduce PM2.5 exposure in China, particularly from outdoor sources. Gender differences and age, period and cohort effects observed in the study provide valuable insights into long-term trends of lung cancer burden attributed to PM2.5.

The impact of air pollutants on spontaneous abortion: a case-control study in Tongchuan City.

OBJECTIVES: Studies related to air pollutants and spontaneous abortion in urban northwestern China are scarce, and the main exposure windows of pollutants acting on pregnant women are unclear. STUDY DESIGN: Case-control study. METHODS: Data were collected from pregnant women in Tongchuan City from 2018 to 2019. A total of 289 cases of spontaneous abortion and 1156 cases of full-term labor were included and analyzed using a case-control study. Logistic regression models were developed to explore the relationship between air pollutants and spontaneous abortion after Chi square analysis and Air pollutant description. RESULTS: O3 (odds ratio [OR] = 1.028) is a risk factor for spontaneous abortion throughout pregnancy. PM2.5 (OR = 1.015), PM10 (OR = 1.010), SO2 (OR = 1.026), and NO2 (OR = 1.028) are risk factors for spontaneous abortion in the 30 days before the last menstrual period. PM2.5 (OR = 1.015), PM10 (OR = 1.013), SO2 (OR = 1.036), and NO2 (OR = 1.033) are risk factors for spontaneous abortion in the 30-60 days before the last menstrual period. PM2.5 (OR = 1.028), PM10 (OR = 1.013), SO2 (OR = 1.035), and NO2 (OR = 1.059) are risk factors for spontaneous abortion in the 60-90 days before the last menstrual period. CONCLUSION: Exposure to high levels of air pollutants may be a cause of increased risk of spontaneous abortion, especially in the first trimester of the last menstrual period.

A risk-prediction score about colorectal lesions based on the Chinese population of high-risk participants aged 50-65 years.

OBJECTIVES: The present study aims to develop an effective risk-prediction score (RPS) to improve screening efficiency and contribute to secondary prevention of colorectal cancer (CRC). STUDY DESIGN: Screening for colorectal lesions. METHODS: 14,398 high-risk individuals aged 50-65 years were included. The baseline characteristics of participants with and without colorectal lesions (CL) were compared using a Chi-squared test. The overall population was randomly split into a training set and a test set in the ratio of 80% and 20%. One-factor and multifactor logistic regression analyses were performed in the training set to construct the RPS (scores of 0-9.62). Area under curve (AUC) was calculated as an estimate of predictive performance using the receiver-operating characteristic (ROC) curve in the test set. RESULTS: In the study population, being male, advanced age, current or previous smoking, weekly alcohol consumption, high body mass index (BMI ≥24 kg/m2), and previously detected colonic polyp were associated with higher risk of CL. Compared to the low-risk group (0-2.31 points), the ORs and 95% confidence intervals (CIs) for the moderate-risk group (2.31-3.85 points) and high-risk group (3.85-8.42 points) were 1.58 (1.44, 1.73) and 2.52 (2.30, 2.76), respectively. For every 1-point increase in score, participants had a 27% increased risk of CL (OR:1.27, 95% CI: 1.24, 1.30). For participants with CL predicted by RPS, the area under the working characteristic curve was 0.61 (P < 0.001). CONCLUSION: Our RPS can quickly and efficiently identify multiple lesions of the colorectum. Combining RPS with existing screening strategies facilitates the identification of very high-risk individuals and may help to prevent CRC.