The evolution and diversification of oakleaf butterflies.

Oakleaf butterflies in the genus Kallima have a polymorphic wing phenotype, enabling these insects to masquerade as dead leaves. This iconic example of protective resemblance provides an interesting evolutionary paradigm that can be employed to study biodiversity. We integrated multi-omic data analyses and functional validation to infer the evolutionary history of Kallima species and investigate the genetic basis of their variable leaf wing patterns. We find that Kallima butterflies diversified in the eastern Himalayas and dispersed to East and Southeast Asia. Moreover, we find that leaf wing polymorphism is controlled by the wing patterning gene cortex, which has been maintained in Kallima by long-term balancing selection. Our results provide macroevolutionary and microevolutionary insights into a model species originating from a mountain ecosystem.

Synthesis and Evaluation of [18F]AlF-NOTA-c-DVAP: A Novel PET Probe for Imaging GRP78 in Cancer.

GRP78, a member of the HSP70 superfamily, is an endoplasmic reticulum chaperone protein overexpressed in various cancers, making it a promising target for cancer imaging and therapy. Positron emission tomography (PET) imaging offers unique advantages in real time, noninvasive tumor imaging, rendering it a suitable tool for targeting GRP78 in tumor imaging to guide targeted therapy. Several studies have reported successful tumor imaging using PET probes targeting GRP78. However, existing PET probes face challenges such as low tumor uptake, inadequate in vivo distribution, and high abdominal background signal. Therefore, this study introduces a novel peptide PET probe, [18F]AlF-NOTA-c-DVAP, for targeted tumor imaging of GRP78. [18F]AlF-NOTA-c-DVAP was radiolabeled with fluoride-18 using the aluminum-[18F]fluoride ([18F]AlF) method. The study assessed the partition coefficients, stability in vitro, and metabolic stability of [18F]AlF-NOTA-c-DVAP. Micro-PET imaging, pharmacokinetic analysis, and biodistribution studies were carried out in tumor-bearing mice to evaluate the probe's performance. Docking studies and pharmacokinetic analyses of [18F]AlF-NOTA-c-DVAP were also performed. Immunohistochemical and immunofluorescence analyses were conducted to confirm GRP78 expression in tumor tissues. The probe's binding affinity to GRP78 was analyzed by molecular docking simulation. [18F]AlF-NOTA-c-DVAP was radiolabeled in just 25 min with a high yield of 51 ± 16%, a radiochemical purity of 99%, and molar activity within the range of 20-50 GBq/µmol. [18F]AlF-NOTA-c-DVAP demonstrated high stability in vitro and in vivo, with a logD value of -3.41 ± 0.03. Dynamic PET imaging of [18F]AlF-NOTA-c-DVAP in tumors showed rapid uptake and sustained retention, with minimal background uptake. Biodistribution studies revealed rapid blood clearance and excretion through the kidneys following a single-compartment reversible metabolic model. In PET imaging, the T/M ratios for A549 tumors (high GRP78 expression), MDA-MB-231 tumors (medium expression), and HepG2 tumors (low expression) at 60 min postintravenous injection were 10.48 ± 1.39, 6.25 ± 0.47, and 3.15 ± 1.15% ID/g, respectively, indicating a positive correlation with GRP78 expression. This study demonstrates the feasibility of using [18F]AlF-NOTA-c-DVAP as a PET tracer for imaging GRP78 in tumors. The probe shows promising results in terms of stability, specificity, and tumor targeting. Further research may explore the clinical utility and potential therapeutic applications of this PET tracer for cancer diagnosis.

Synthesis and preclinical evaluation of a novel probe [18F]AlF-NOTA-IPB-GPC3P for PET imaging of GPC3 positive tumor.

Glypican-3 (GPC3) is markedly overexpressed in hepatocellular carcinoma (HCC) and not expressed in normal liver tissues. In this study, a novel peptide PET imaging agent ([18F]AlF-NOTA-IPB-GPC3P) was developed to target GPC3 expressed in tumors. The overall radiochemical yield of [18F]AlF-NOTA-IPB-GPC3P was 10-15 %, and its lipophilicity, expressed as the logD value at a pH of 7.4, was -1.18 ± 0.06 (n = 3). Compared to the previously reported tracer [18F]AlF-GP2633, [18F]AlF-NOTA-IPB-GPC3P exhibited higher cellular uptake (15.13 vs 5.96) and internalized rate (80.63 % vs 35.93 %) in Huh7 cells at 120 min. Micro-PET/CT and biodistribution studies further demonstrated that [18F]AlF-NOTA-IPB-GPC3P exhibited significantly increased tumor uptake and prolonged tumor residence in Huh7 tumors compared to [18F]AlF-GP2633 (4.66 ± 0.22 % ID/g vs 0.72 ± 0.09 % ID/g at 60 min, p < 0.001; 5.05 ± 0.23 % ID/g vs 0.35 ± 0.08 % ID/g at 120 min, p < 0.001, respectively). Furthermore, the tumor-to-organ ratios of [18F]AlF-NOTA-IPB-GPC3P surpassed those of [18F]AlF-GP2633. Our results support the utilization of [18F]AlF-NOTA-IPB-GPC3P as a PET imaging agent targeting the GPC3 receptor for tumor detection.

Development and external validation of a nomogram for the early prediction of acute kidney injury in septic patients: a multicenter retrospective clinical study.

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

The predictors of long-term outcomes after targeted therapy for primary Aldosteronism.

Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery.

Network Analysis Indicates Microbial Assemblage Differences in Life Stages of Cladophora.

Cladophora represents a microscopic forest that provides many ecological niches and fosters a diverse microbiota. However, the microbial community on Cladophora in brackish lakes is still poorly understood. In this study, the epiphytic bacterial communities of Cladophora in Qinghai Lake were investigated at three life stages (attached, floating, and decomposing). We found that in the attached stage, Cladophora was enriched with chemoheterotrophic and aerobic microorganisms, including Yoonia-Loktanella and Granulosicoccus. The proportion of phototrophic bacteria was higher in the floating stage, especially Cyanobacteria. The decomposing stage fostered an abundance of bacteria that showed vertical heterogeneity from the surface to the bottom. The surface layer of Cladophora contained mainly stress-tolerant chemoheterotrophic and photoheterotrophic bacteria, including Porphyrobacter and Nonlabens. The microbial community in the middle layer was similar to that of floating-stage Cladophora. Purple oxidizing bacteria were enriched in the bottom layer, with Candidatus Chloroploca, Allochromatium, and Thiocapsa as the dominant genera. The Shannon and Chao1 indices of epibiotic bacterial communities increased monotonically from the attached stage to the decomposing stage. Microbial community composition and functional predictions indicate that a large number of sulfur cycle-associated bacteria play an important role in the development of Cladophora. These results suggest that the microbial assemblage on Cladophora in a brackish lake is complex and contributes to the cycling of materials. IMPORTANCE Cladophora represents a microscopic forest that provides many ecological niches fostering a diverse microbiota, with a complex and intimate relationship between Cladophora and bacteria. Many studies have focused on the microbiology of freshwater Cladophora, but the composition and succession of microorganisms in different life stages of Cladophora, especially in brackish water, have not been explored. In this study, we investigated the microbial assemblages in the life stages of Cladophora in the brackish Qinghai Lake. We show that heterotrophic and photosynthetic autotrophic bacteria are enriched in attached and floating Cladophora, respectively, whereas the epiphytic bacterial community shows vertical heterogeneity in decomposing mats.

Noninvasive imaging of FAP expression using positron emission tomography: A comparative evaluation of a [18F]-labeled glycopeptide-containing FAPI with [18F]FAPI-42.

PURPOSE: Research on fibroblast activating protein (FAP)-targeting inhibitor (FAPI) has become an important focus for cancer imaging and radiotherapy. Quinoline-based tracers [68 Ga]FAPI-04 and [18F]FAPI-42 have been widely used for positron emission tomography (PET) imaging of most tumors. However, there exist some limitations of these tracers with high uptake in biliary duct system and unstable uptake in pancreas, unsuitable for abdominal tumors PET imaging. Here we developed a [18F]-labeled glycopeptide-containing FAPI tracer (named [18F]FAPT) for PET imaging of FAP in cancers. METHODS: [18F]FAPT was synthesized manually and automatically. The competitive binding to FAP, cellular internalization, and efflux characteristics were examined in vitro using A549-FAP cells. Dynamic MicroPET and biodistribution studies of [18F]FAPT were then conducted in A549-FAP and U87MG xenograft tumor mouse models compared with [18F]FAPI-42. Five healthy volunteers and three patients with cancer underwent [18F]FAPT PET/CT. RESULTS: Preclinical and clinical studies showed specific binding of [18F]FAPT to FAP and favorable pharmacokinetic properties with better hydrophilicity, lower uptake in biliary duct system, higher tumor uptake and longer tumor retention compared with [18F]FAPI-42. The biodistribution of [18F]FAPT in healthy volunteers and patients with cancer displayed low uptake in most normal tissues except for pancreas, thyroid and salivary gland, which could contribute to high tumor-to-background ratios in most cancers. CONCLUSION: [18F]FAPT is better PET tracer than [18F]FAPI-42 for imaging of biliary duct system cancer, potentially providing a tool to examine FAP expression in most cancers with high tumor-to-background ratios.

Pharmacokinetic analysis of 6-O-[18F]FEE for PET imaging of EGFR mutation.

6-O-[18F]Fluoroethylerlotinib (6-O-[18F]FEE), with a suitable half-life for commercial distribution, may be a good replacement for [11C]erlotinib to identify epidermal growth factor receptor (EGFR) positive tumors with activating mutations to tyrosine kinase inhibitors therapy. In this study, we explored the fully automated synthesis of 6-O-[18F]FEE and investigated its pharmacokinetics in tumor-bearing mice. 6-O-[18F]FEE with high specific activity (28-100 GBq/µmol) and radiochemistry purity (over 99 %) was obtained by two-step reaction and Radio-HPLC separation in PET-MF-2 V-IT-1 automated synthesizer. PET imaging of 6-O-[18F]FEE in HCC827, A431, and U87 tumor-bearing mice with different EGFR expression and mutation was performed. Uptake and blocking of PET imaging indicated that the probe specifically targeted exon 19 deleted EGFR (the quantitative analysis of tumor-to-mouse ratio for HCC827, HCC827 blocking, U87, A431 was 2.58 ± 0.24, 1.20 ± 0.15, 1.18 ± 0.19, and 1.05 ± 0.13 respectively). Dynamic imaging was used to study the pharmacokinetics of the probe in tumor-bearing mice. Logan plot graphical analysis demonstrated late linearity and a high fitting correlation coefficient (0.998), supporting reversible kinetics. According to the Akaike Information Criterion (AIC) rule, the 2-compartment reversible model was more consistent with the metabolic properties of 6-O-[18F]FEE. The automated radiosynthesis and pharmacokinetic analysis will promote clinically transformation of 6-O-[18F]FEE.

Aggregation-Induced emission photosensitizer with lysosomal response for photodynamic therapy against cancer.

Photosensitizers play a key role in bioimaging and photodynamic therapy (PDT) of cancer. However, conventional photosensitizers usually do not achieve the desired efficacy in PDT due to their poor photostability, targeting ability, and responsiveness. Herein, we designed a series of photosensitizers with aggregation-induced emission (AIE) effect using benzothiazole- triphenylamine (BZT-triphenylamine) as the parent nucleus. The synthesized compound SIN ((E)-2-(4-(diphenylamino)styryl)-3-(4-iodobutyl)benzo[d]thiazol-3-ium) exhibits good biocompatibility, photostability, and bright emission in the near-infrared range (600-800 nm). The fluorescence emission intensity is responsive to viscosity, with significant fluorescence enhancement (48 times) and high fluorescence quantum yield (4.45 %) at high viscosity. Moreover, SIN has particular lysosome targeting properties with a Pearson correlation coefficient (PCC) of 0.97 and has good 1O2 generation ability under white light irradiation, especially in a weak acidic environment. Thus, SIN can realize good bioimaging ability and photodynamic therapeutic efficacy under the highly viscous and weakly acidic environment of lysosomes in the tumor cells. This study indicates that SIN has potential as a multifunctional organic photosensitizer for bioimaging and PDT of tumor.

Clinical presentations and outcomes of pancreaticobiliary maljunction in different pediatric age groups.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a congenital defect, with risk of developing various pancreaticobiliary and hepatic complications. The presentations of PBM in children and adults are believed to be different, but studies on PBM children of different age groups are limited. This study was to evaluate clinicopathologic characteristics and outcomes in PBM children of different ages. METHODS: A total of 166 pediatric patients with PBM were reviewed retrospectively. Clinicopathological, imaging, laboratory, surgical, and follow-up data were collected and analyzed. The patients were divided into three age groups, namely, group A (< 1 year, n = 31), group B (1-3 years, n = 63), and group C (> 3 years, n = 72). RESULTS: The major clinical manifestation was jaundice in group A and abdominal pain and vomiting in groups B and C. Acute pancreatitis was more often seen in group C than group A. The length of common channel was significantly longer in group C than group A, while the maximum diameter of common bile duct in group C was smaller than that in group A. Cholangitis and cholecystitis were more commonly performed in groups B and C, while hepatic fibrosis in group A. Whether preoperatively or postoperatively, group C was more likely to have elevated serum amylase, while groups A and B were more likely to present with abnormal liver function indicators, including the increase of aspartate transaminase, alanine transaminase, and gamma-glutamyl transpeptidase. CONCLUSION: Presentation of PBM varies among different pediatric age groups, thus suggesting that targeted management should be carried out according to these differences.

Identification and validation of radiomic features from computed tomography for preoperative classification of neuroblastic tumors in children.

BACKGROUND: To identify radiomic features that can predict the pathological type of neuroblastic tumor in children. METHODS: Data on neuroblastic tumors in 104 children were retrospectively analyzed. There were 14 cases of ganglioneuroma, 24 cases of ganglioneuroblastoma, and 65 cases of neuroblastoma. Stratified sampling was used to randomly allocate the cases into the training and validation sets in a ratio of 3:1. The maximum relevance-minimum redundancy algorithm was used to identify the top 10 of two clinical features and 851 radiomic features in portal venous-phase contrast-enhanced computed tomography images. Least absolute shrinkage and selection operator regression was used to classify tumors in two binary steps: first as ganglioneuroma compared to the other two types, then as ganglioneuroblastoma compared to neuroblastoma. RESULTS: Based on 10 clinical-radiomic features, the classifier identified ganglioneuroma compared to the other two tumor types in the validation dataset with sensitivity of 100.0%, specificity of 81.8%, and an area under the receiver operating characteristic curve (AUC) of 0.875. The classifier identified ganglioneuroblastoma versus neuroblastoma with a sensitivity of 83.3%, a specificity of 87.5%, and an AUC of 0.854. The overall accuracy of the classifier across all three types of tumors was 80.8%. CONCLUSION: Radiomic features can help predict the pathological type of neuroblastic tumors in children.

Using machine learning models to predict the surgical risk of children with pancreaticobiliary maljunction and biliary dilatation.

PURPOSE: To develop machine learning (ML) models to predict the surgical risk of children with pancreaticobiliary maljunction (PBM) and biliary dilatation. METHODS: The subjects of this study were 157 pediatric patients who underwent surgery for PBM with biliary dilatation between January, 2015 and August, 2022. Using preoperative data, four ML models were developed, including logistic regression (LR), random forest (RF), support vector machine classifier (SVC), and extreme gradient boosting (XGBoost). The performance of each model was assessed via the area under the receiver operator characteristic curve (AUC). Model interpretations were generated by Shapley Additive Explanations. A nomogram was used to validate the best-performing model. RESULTS: Sixty-eight patients (43.3%) were classified as the high-risk surgery group. The XGBoost model (AUC = 0.822) outperformed the LR (AUC = 0.798), RF (AUC = 0.802) and SVC (AUC = 0.804) models. In all four models, enhancement of the choledochal cystic wall and an abnormal position of the right hepatic artery were the two most important features. Moreover, the diameter of the choledochal cyst, bile duct variation, and serum amylase were selected as key predictive factors by all four models. CONCLUSIONS: Using preoperative data, the ML models, especially XGBoost, have the potential to predict the surgical risk of children with PBM and biliary dilatation. The nomogram may provide surgeons early warning to avoid intraoperative iatrogenic injury.

Virulence, Aggressiveness, and Fungicide Sensitivity of Phytophthora spp. Associated with Soybean in Illinois.

Phytophthora root and stem rot (PRR), caused by Phytophthora sojae, is one of the most devastating oomycete diseases of soybean in Illinois. Single resistant genes (Rps) are used to manage this pathogen but P. sojae has adapted to Rps, causing failure of resistance in many regions. In addition to P. sojae, recent reports indicate that P. sansomeana could also cause root rot in soybean. Soil samples and symptomatic plants were collected across 40 Illinois counties between 2016 and 2018. P. sojae (77%) was more abundant than P. sansomeana (23%) across Illinois fields. Both species were characterized by virulence, aggressiveness, and fungicide sensitivity. Virulence of all P. sojae isolates was evaluated using the hypocotyl inoculation technique in 13 soybean differentials. Aggressiveness was evaluated in the greenhouse by inoculating a susceptible cultivar and measuring root and shoot dry weight. On average, P. sojae isolates were able to cause disease on six soybean differentials. P. sojae was more aggressive than P. sansomeana. All isolates were sensitive to azoxystrobin, ethaboxam, mefenoxam, and metalaxyl. The characterization of the population of species associated with PRR will inform management decisions for this disease in Illinois.

Prediction of post-operative acute pancreatitis in children with pancreaticobiliary maljunction using machine learning model.

PURPOSE: This study aimed to develop a prediction model to identify risk factors for post-operative acute pancreatitis (POAP) in children with pancreaticobiliary maljunction (PBM) by pre-operative analysis of patient variables. METHODS: Logistic regression (LR), support vector machine (SVM), and extreme gradient boosting (XGBoost) models were established using the prospectively collected databases of patients with PBM undergoing surgery which was reviewed in the period comprised between August 2015 and August 2022, at the Children's Hospital of Soochow University. Primarily, the area beneath the receiver-operating curves (AUC), accuracy, sensitivity, and specificity were used to evaluate the model performance. The model was finally validated using the nomogram and clinical impact curve. RESULTS: In total, 111 children with PBM met the inclusion criteria, and 21 children suffered POAP. In the validation dataset, LR models showed the highest performance. The risk nomogram and clinical effect curve demonstrated that the LR model was highly predictive. CONCLUSION: The prediction model based on the LR with a nomogram could be used to predict the risk of POAP in patients with PBM. Protein plugs, age, white blood cell count, and common bile duct diameter were the most relevant contributing factors to the models.

Comparing individual-, family-, and community-level effects on the oral health of preschool children: a multilevel analysis of national survey data.

BACKGROUND: Early childhood is a critical stage for the prevention of dental caries. The prevalence of caries in preschool children is still high in Taiwan, where National Health Insurance covers 99% of the population. The effort to improve the oral health of preschool children should be based on conceptual model that encompasses more than individual-level factors. This study input nationwide survey data in a conceptual model to evaluate the effects of comprehensive factors related to the high prevalence of caries in preschool children. METHODS: This observation study examined factors related to the oral health of preschool children by employing a comprehensive multilevel model to analyse nationally representative data from the Taiwan Oral Health Survey of Preschool Children (TOHPC) 2017-2018. Individual-level, family-level and community-level contextual effects were evaluated through multilevel analysis in this study. The proportional change in variance (PCV) was used to compare the multilevel model with the null model and individual-level, family-level, and community-level context effects. RESULTS: The estimated deft index for preschool children was 1.34 (1.22-1.47) at age 3, 2.20 (2.08-2.32) at age 4, and 3.05 (2.93-3.18) at age 5. The overall prevalence of caries in preschool children in Taiwan was 34.27% (30.76%, 37.78%) at age 3, 51.67% (48.99%, 54.35%) at age 4, and 62.05% (59.66%, 64.44%) at age 5. The model that included the individual-, family-, and community-context levels exhibited the highest reduction of variance (PCV = 53.98%). The PCV was further reduced to 35.61% when only the level of accessibility to dental services for individuals, families, and the community was considered. For the model in which no community-context cofactors were considered and the model considering only the individual level, the PCVs were 20.37% and 5.52%, respectively. CONCLUSIONS: Our findings indicate the key components that affect oral health in preschool children and can serve as a reference for policy makers. The most notable finding of this study is that to improve the oral health of preschool children, community-level factors should be targeted. To rely solely on dentists for leading oral health education programs for children is impractical and inefficient. Training more professional oral health educators to provide additional community-based oral health promotion campaigns is critical. We suggest training more professional oral health educators to provide more community-based oral health promotion campaigns.

Comparison of 68Ga-FAPI and 18F-FDG PET/CT in the Evaluation of Advanced Lung Cancer.

Background Gallium 68 (68Ga)-labeled fibroblast-activation protein inhibitor (FAPI) has recently been introduced as a promising tumor imaging agent. Purpose To compare 68Ga-FAPI PET/CT with fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) PET/CT in evaluating lung cancer. Materials and Methods In this prospective study conducted from September 2020 to February 2021, images from participants with lung cancer who underwent both 68Ga-FAPI and 18F-FDG PET/CT examinations were analyzed. The tracer uptakes, quantified by maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR), were compared for paired positive lesions between both modalities using the paired t test or Wilcoxon signed-rank test. Results Thirty-four participants (median age, 64 years [interquartile range: 46-80 years]; 20 men) were evaluated. From visual evaluation, 68Ga-FAPI PET/CT and 18F-FDG PET/CT showed similar performance in the delineation of primary tumors and detection of suspected metastases in the lungs, liver, and adrenal glands. The metabolic tumor volume in primary and recurrent lung tumors showed no difference between modalities (mean: 11.6 vs 10.8, respectively; P = .68). However, compared with 18F-FDG PET/CT, 68Ga-FAPI PET/CT depicted more suspected metastases in lymph nodes (356 vs 320), brain (23 vs 10), bone (109 vs 91), and pleura (66 vs 35). From semiquantitative evaluation, the SUVmax and TBR of primary or recurrent tumors, positive lymph nodes, bone lesions, and pleural lesions at 68Ga-FAPI PET/CT were all higher than those at 18F-FDG PET/CT (all P < .01). Although SUVmax of 68Ga-FAPI and 18F-FDG in brain metastases were not different (mean SUVmax: 9.0 vs 7.4, P = .32), TBR was higher with 68Ga-FAPI than with 18F-FDG (mean: 314.4 vs 1.0, P = .02). Conclusion Gallium 68-labeled fibroblast-activation protein inhibitor PET/CT may outperform fluorine 18-labeled fluorodeoxyglucose PET/CT in staging lung cancer, particularly in the detection of metastasis to the brain, lymph nodes, bone, and pleura. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Jacobson and Van den Abbeele in this issue.

Genomic regions associated with virulence in Setosphaeria turcica identified by linkage mapping in a biparental population.

Northern corn leaf blight (NCLB) and sorghum leaf blight (SLB) are significant diseases of maize and sorghum, respectively, caused by the filamentous fungus Setosphaeria turcica. Strains of S. turcica are typically host-specific and infect either maize or sorghum. Host specificity in this pathogen is attributed to a single locus for maize and a second distinct locus for sorghum. To identify the genetic basis of host specificity in S. turcica, we generated a biparental population of S. turcica by crossing strains specific to maize and sorghum, phenotyped the population for leaf blight on sorghum and maize, genotyped the population to create a linkage map of S. turcica, and located candidate virulence regions. A total of 190 ascospores from 35 pseudothecia were isolated from the cross of maize and sorghum-specific strains. Greenhouse phenotyping of the biparental population (n = 144) showed independent inheritance of virulence, as indicated by a 1:1:1:1 segregation for virulence to maize, sorghum, both maize and sorghum, and avirulence to both crops. The population and host-specific parent strains were genotyped using genome skim sequencing on an Illumina NovaSeq 6000 platform resulting in over 780 million reads. A total of 32,635 variants including single nucleotide polymorphisms and indels were scored. There was evidence for a large deletion in the sorghum-specific strain of S. turcica. A genetic map consisting of 17 linkage groups spanning 3,069 centimorgans was constructed. Virulence to sorghum and maize mapped on distinct linkage groups with a significant QTL detected for virulence to maize. Furthermore, a single locus each for the in vitro traits hyphal growth rate and conidiation were identified and mapped onto two other linkage groups. In vitro traits did not correlate with in planta virulence complexity, suggesting that virulence on both hosts does not incur a fitness cost. Hyphal growth rate and conidiation were negatively correlated, indicating differences in hyphal growth versus dispersal ability for this pathogen. Identification of genetic regions underlying virulence specificity and saprotrophic growth traits in S. turcica provides a better understanding of the S. turcica- Andropogoneae pathosystem.

Incidence of and risk factors for liver damage in patients with HIV-1 mono-infection receiving antiretroviral therapy.

OBJECTIVES: The study aimed to investigate the incidence of and risk factors for liver damage in patients with human immunodeficiency virus type-1 (HIV-1) mono-infection receiving antiretroviral therapy (ART). METHODS: We retrospectively analyzed the clinical data of patients who were diagnosed with HIV-1 infection and initiated ART from January to December 2017. Among them, 382 patients with HIV-1 mono-infection and normal baseline liver function were included in the analysis. The incidence of liver damage at each follow-up point, and possible risk factors for liver damage were evaluated via COX regression survival analyses. RESULTS: The overall incidence of liver damage (grade I-IV) was 27.23% (interquartile range [IQR]: 26.38%-28.72%). Grade I liver damage was most common and accounted for 22.13% of cases (IQR: 21.06%-24.04%), while grade II liver damage accounted for 3.40% of cases (IQR: 3.19%-4.26%). COX regression and survival analyses revealed that baseline body mass index (BMI), alanine aminotransferase (ALT) level, CD4+ T cell count, HIV-1 viral load, and the antiretroviral regimen were significantly correlated with the occurrence of liver damage. Moreover, baseline ALT levels and HIV-1 viral load were identified as independent risk factors for liver damage in patients with HIV-1 mono-infection. CONCLUSION: Liver damage is common in patients with HIV-1 mono-infection undergoing ART. Patients with risk factors for liver damage should be well-informed before the initiation of ART, and liver function should be closely monitored during ART even in patients with normal liver function before ART.

[18F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [68Ga]Ga-FAPI-04.

PURPOSE: [18F]FAPI-42 is a new fibroblast activation protein (FAP)-specific tracer used for cancer imaging. Here, we describe the optimal acquisition time and in vivo evaluation of [18F]FAPI-42 and compared intra-individual biodistribution, tumor uptake, and detection ability to [68Ga]Ga-FAPI-04. METHODS: A total of 22 patients with various types of cancer received [18F]FAPI-42 whole-body positron emission tomography/computed tomography (PET/CT). Among them, 4 patients underwent PET/CT scans, including an early dynamic 20-min, static 1-h, and static 2-h scans. The in vivo biodistribution in normal organs and tumor uptake were semiquantitatively evaluated using the standardized uptake value (SUV) and tumor-to-background ratio (TBR). Furthermore, both [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT were performed in 12 patients to compare biodistribution, tumor uptake, and tumor detection ability. RESULTS: [18F]FAPI-42 uptake in the tumors was rapid and reached a high level with an average SUVmax of 15.8 at 18 min, which stayed at a similarly high level to 2 h. The optimal image acquisition time for [18F]FAPI-42 was determined to be 1 h postinjection. For tumor detection, [18F]FAPI-42 had a high uptake and could be clearly visualized in the lesions. Compared to [68Ga]Ga-FAPI-04, [18F]FAPI-42 had the same detectability for 144 positive lesions. In addition, [18F]FAPI-42 showed a higher SUVmax in liver and bone lesions (P < 0.05) and higher TBRs in liver, bone, lymph node, pleura, and peritoneal lesions (all P < 0.05). CONCLUSION: The present study demonstrates that the optimal image acquisition time of [18F]FAPI-42 is 1 h postinjection and that [18F]FAPI-42 exhibits comparable lesion detectability to [68Ga]Ga-FAPI-04. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100045757).

End-to-end interstitial fibrosis assessment of kidney biopsies with a machine learning-based model.

BACKGROUND: The extent of interstitial fibrosis in the kidney not only correlates with renal function at the time of biopsy but also predicts future renal outcome. However, its assessment by pathologists lacks good agreement. The aim of this study is to construct a machine learning-based model that enables automatic and reliable assessment of interstitial fibrosis in human kidney biopsies. METHODS: Validated cortex, glomerulus and tubule segmentation algorithms were incorporated into a single model to assess the extent of interstitial fibrosis. The model performances were compared with expert renal pathologists and correlated with patients' renal functional data. RESULTS: Compared with human raters, the model had the best agreement [intraclass correlation coefficient (ICC) 0.90] to the reference in 50 test cases. The model also had a low mean bias and the narrowest 95% limits of agreement. The model was robust against colour variation on images obtained at different times, through different scanners, or from outside institutions with excellent ICCs of 0.92-0.97. The model showed significantly better test-retest reliability (ICC 0.98) than humans (ICC 0.76-0.94) and the amount of interstitial fibrosis inferred by the model strongly correlated with 405 patients' serum creatinine (r = 0.65-0.67) and estimated glomerular filtration rate (r = -0.74 to -0.76). CONCLUSIONS: This study demonstrated that a trained machine learning-based model can faithfully simulate the whole process of interstitial fibrosis assessment, which traditionally can only be carried out by renal pathologists. Our data suggested that such a model may provide more reliable results, thus enabling precision medicine.