Enhancing trainee performance in obstetric ultrasound through an artificial intelligence system: randomized controlled trial.

OBJECTIVE: Performing obstetric ultrasound scans is challenging for inexperienced operators; therefore, the prenatal screening artificial intelligence system (PSAIS) software was developed to provide real-time feedback and guidance for trainees during their scanning procedures. The aim of this study was to investigate the potential benefits of utilizing such an artificial intelligence system to enhance the efficiency of obstetric ultrasound training in acquiring and interpreting standard basic views. METHODS: A prospective, single-center randomized controlled study was conducted at The First Affiliated Hospital of Sun Yat-sen University. From September 2022 to April 2023, residents with no prior obstetric ultrasound experience were recruited and assigned randomly to either a PSAIS-assisted training group or a conventional training group. Each trainee underwent a four-cycle practical scan training program, performing 20 scans in each cycle on pregnant volunteers at 18-32 gestational weeks, focusing on acquiring and interpreting standard basic views. At the end of each cycle, a test scan evaluated trainees' ability to obtain standard ultrasound views without PSAIS assistance, and image quality was rated by both the trainees themselves and an expert (in a blinded manner). The primary outcome was the number of training cycles required for each trainee to meet a certain standard of proficiency (i.e. end-of-cycle test scored by the expert at ≥ 80%). Secondary outcomes included the expert ratings of the image quality in each trainee's end-of-cycle test and the discordance between ratings by trainees and the expert. RESULTS: In total, 32 residents and 1809 pregnant women (2720 scans) were recruited for the study. The PSAIS-assisted trainee group required significantly fewer training cycles compared with the non-PSAIS-assisted group to meet quality requirements (P = 0.037). Based on the expert ratings of image quality, the PSAIS-assisted training group exhibited superior ability in acquiring standard imaging views compared with the conventional training group in the third (P = 0.012) and fourth (P < 0.001) cycles. In both groups, the discordance between trainees' ratings of the quality of their own images and the expert's ratings decreased with increasing training time. A statistically significant difference in overall trainee-expert rating discordance between the two groups emerged at the end of the first training cycle and remained at every cycle thereafter (P < 0.013). CONCLUSION: By assisting inexperienced trainees in obtaining and interpreting standard basic obstetric scanning views, the use of artificial intelligence-assisted systems has the potential to improve training effectiveness. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

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.

Bronchiolar adenoma/ciliated muconodular papillary tumour: advancing clinical, pathological, and imaging insights for future perspectives.

Bronchiolar adenoma/ciliated muconodular papillary tumour (BA/CMPT) is a benign peripheral lung tumour composed of bilayered bronchiolar-type epithelium containing a continuous basal cell layer; however, the similarities in imaging and tissue biopsy findings at histopathology between BA/CMPT and malignant tumours, including lung adenocarcinoma, pose significant challenges in accurately diagnosing BA/CMPT preoperatively. This difficulty in differentiation often results in misdiagnosis and unnecessary overtreatment. The objective of this article is to provide a comprehensive and systematic review of BA/CMPT, encompassing its clinical manifestations, pathological basis, imaging features, and differential diagnosis. By enhancing healthcare professionals' understanding of this disease, we aim to improve the accuracy of preoperative BA/CMPT diagnosis. This improvement is crucial for the development of appropriate therapeutic strategies and the overall improvement of patient prognosis.

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.

Risk of metastasis and survival in patients undergoing different treatment strategies with T1 colonic neuroendocrine tumors.

PURPOSE: The efficacy and safety of local excision (LE) for small (< 1‒2 cm) colonic neuroendocrine tumors (NETs) is controversial due to the higher metastasis risk when compared with rectal NETs. The study aimed to evaluate the metastasis risk of T1 colonic NETs and compare patients' long-term prognosis after LE or radical surgery (RS). METHODS: The Surveillance Epidemiology and End Results database was used to identify patients with T1 colonic NETs (2004‒2015). Multivariable logistic regression was performed to assess factors associated with metastasis risk. Propensity score matching was used to balance the variables. Cancer-specific survival (CSS) and overall survival (OS) were calculated to estimate the prognosis of patients with T1N0M0 colonic NETs who underwent LE or RS. RESULTS: Of the 610 patients with colonic NETs, 46 (7.54%) had metastasis at diagnosis. Tumor size (11-20 mm) (OR = 9.51; 95% confidence interval (CI): 4.32‒21.45; P < 0.001), right colon (OR = 15.79; 95% CI 7.20‒38.56; P < 0.001), submucosal infiltration (OR = 2.08; 95% CI 0.84‒5.57; P = 0.125) were independent risk factors associated with metastasis. Of the 515 patients with T1N0M0 colonic NETs, the overall long-term prognosis of LE was as good as that of RS groups (after matching, 5-year CSS: 97.9% vs. 94.6%, P = 0.450; 5-year OS: 92.7% vs. 85.6%, P = 0.009). CONCLUSION: Tumor size (11‒20 mm) and site (right colon) are associated with metastasis in T1 colonic NETs. In the absence of metastasis, LE could be a viable option for 0‒10 mm T1 colonic NETs with well/moderate differentiation in the left colon in terms of long-term survival.

Tensile forces in the neurovascular bundle: A contributor to orthodontic relapse?

OBJECTIVES: The aim of this study is to investigate the neurovascular bundle (NVB) as a potential orthodontic relapse factor. The mechanical properties and the forces generated in the NVB after orthodontic extrusion are explored. MATERIALS AND METHODS: Six NVBs branching from the inferior alveolar nerve to the apices of the mandibular canines and premolars of mature pigs were harvested. Stress relaxation tests were conducted. A standard linear solid model (SLS) was utilized to simulate the orthodontic extrusion of a single rooted tooth with NVB length and cross-sectional diameter of 3.6 and 0.5 mm, respectively, so the NVB was stretched 10% and 20% of its original length. The maximum force within the NVB was then calculated. RESULTS: Based on our data, the average Young's modulus before relaxation ( E 0 ), after relaxation ( E P ) and the difference between Young's moduli before and after relaxation ( E S ) were 324 ± 123, 173 ± 73 and 151 ± 52 kPa, respectively. The theoretical force within the NVB stretched to 10% and 20% strain was 3 and 5 mN, respectively. CONCLUSION: The data from our study indicate that the NVB exhibits stress relaxation, a characteristic trait of viscoelastic materials. SLS model simulation predicted residual forces around 5 mN for elongation up to 20%. We observed strain hardening with additional elongation, which has the potential to cause forces to increase exponentially. Therefore, tensile forces in the NVB should not be ruled out as a contributor to orthodontic relapse, especially in adult patients who may have decreased adaptability of their NVB. Further preclinical and clinical models should be developed to further clarify what is the contribution of the NVB to orthodontic relapse.

[Clinical characteristics analysis of heterotopic cervical pregnancy].

Objective: To investigate the clinical characteristics of heterotopic cervical pregnancy (HCP). Methods: A retrospective analysis was conducted based on the general clinical data, assisted reproductive technology (ART) data, diagnosis and treatment data, and pregnancy outcomes of 17 patients diagnosed with HCP who received ART at the Reproductive Medicine Center of Peking University Third Hospital from January 2011 to April 2022. Results: The age of 17 HCP patients was (34.2±1.5) years, all of whom occurred after the application of ART; Among them, 11 cases had a history of uterine cavity operation. All 17 patients had vaginal bleeding, with only 1 case accompanied by abdominal pain. The gestational age at the diagnosis of HCP was [6+2 (5+2-6+4)] weeks. Two patients underwent conservative observation and were closely followed up. Both of them had intrauterine pregnancy until full-term and underwent cesarean section; One patient underwent ultrasound-guided cervical pregnancy reduction surgery, resulting in miscarriage due to premature rupture of membranes at 18+1 weeks of intrauterine pregnancy; One patient underwent ultrasound-guided cervical pregnancy reduction surgery, followed by uterine artery embolization, hysteroscopy, removal of cervical pregnancy lesions, and curettage due to excessive bleeding; One patient underwent uterine artery embolization, hysteroscopy, cervical pregnancy lesion clearance, and curettage due to excessive vaginal bleeding; One patient underwent hysteroscopy examination, cervical pregnancy lesion removal surgery, and uterine curettage due to embryo arrest during intrauterine pregnancy; 11 cases underwent ultrasound-guided cervical pregnancy lesion clearance surgery, all of which resulted in live births. Among the 13 delivery patients, 4 cases were premature and 9 cases were full-term; 5 cases of vaginal delivery and 8 cases of cesarean section. Conclusions: The most common clinical manifestation of HCP is vaginal bleeding. Ultrasound guided cervical pregnancy lesion clearance surgery is safe and feasible, and with good pregnancy outcomes.

[Rudimentary horn pregnancy: clinical analysis of 12 cases and literature review].

Objective: To investigate the clinical characteristics, treatments and fertility recovery of rudimentary horn pregnancy (RHP). Methods: The clinical data of 12 cases with RHP diagnosed and treated in Peking University Third Hospital from January 1, 2010 to December 31, 2022 were retrospectively analyzed. Clinical informations, diagnosis and treatments of RHP and the pregnancy status after surgery were analyzed. Results: The median age of 12 RHP patients was 29 years (range: 24-37 years). Eight cases of pregnancy in residual horn of uterus occurred in type Ⅰ residual horn of uterus, 4 cases occurred in type Ⅱ residual horn of uterus; among which 5 cases were misdiagnosed by ultrasound before surgery. All patients underwent excision of residual horn of uterus and affected salpingectomy. After surgery, 9 patients expected future pregnancy, and 3 cases of natural pregnancy, 2 cases of successful pregnancy through assisted reproductive technology. Four pregnancies resulted in live birth with cesarean section, and 1 case resulted in spontaneous abortion during the first trimester of pregnancy. No uterine rupture or ectopic pregnancy occurred in subsequent pregnancies. Conclusions: Ultrasonography could aid early diagnosis of RHP while misdiagnosis occurred in certain cases. Thus, a comprehensive judgment and decision ought to be made based on medical history, physical examination and assisted examination. Surgical exploration is necessary for diagnosis and treatment of RHP. For infertile patients, assisted reproductive technology should be applied when necessary. Caution to prevent the occurrence of pregnancy complications such as uterine rupture, and application of cesarean section to terminate pregnancy are recommended.

[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

[The mechanism of berberine on Methicillin resistant Staphylococcus aureus in vitro].

Objective: To explore the impact of traditional Chinese medicine berberine (BBR) on membrane integrity and permeability of Methicillin-resistant Staphylococcus aureus (MRSA) and the change of bacterial cell wall structure, laying a foundation for the clinical application of berberine in antibacterial. Methods: This study used a non-randomized concurrent controlled trial. The 3 MRSA strains were isolated and cultured from lower respiratory tract samples of geriatric patients from Shanghai Eighth People's Hospital between 2019 and 2020.The Meirier VETEK MS fully automated rapid microbial mass spectrometry detection system and VETEK 2 Compact fully automated microbial identification instrument were used to identify bacterial drug sensitivity experiments to detect bacterial species and drug sensitivity. The minimal inhibitory concentration (MIC) of BBR on MRSA strains was determined by broth microdilution. This study used conductivity tests to assess the changes in membrane permeability in response to different concentration of BBR on MRSA, while also investigating the changes in MRSA morphology by transmission electron microscopy. GraphPad Prism5 was used to analyze the differences in the electrical conductivity experimental results. Results: The MIC of BBR on MRSA was 64 µg/ml. After co-culturing MRSA with BBR for 4 h at 8 µg/ml, 16 µg/ml, 32 µg/ml, 64 µg/ml and 128 µg/ml, respectively, the electrical conductivity increased, compared with the control group, by 24.49%,34.59%,208.92%,196.40% and 208.68%, respectively. By transmission electron microscopy, This study found that low concentration of BBR (8 µg/ml,1/8 MIC) caused no significant damage to MRSA, and the bacterial structure of MRSA remained intact. The cell wall of MRSA became thinner after treatment with berberine at medium concentration (64 µg/ml,1 MIC), while high concentration of BBR (512 µg/ml,8 MIC) induced the destruction and dissolution of MRSA cell wall structure and the leakage of bacterial contents, leading to bacterial lysis. Conclusion: Berberine can kill bacteria by altering the permeability of MRSA cell membrane and destroying and dissolving the structure of the cell wall.

[Latent period and incubation period with associated factors of COVID-19 caused by Omicron variant].

Objective: To estimate the latent period and incubation period of Omicron variant infections and analyze associated factors. Methods: From January 1 to June 30, 2022, 467 infections and 335 symptomatic infections in five local Omicron variant outbreaks in China were selected as the study subjects. The latent period and incubation period were estimated by using log-normal distribution and gamma distribution models, and the associated factors were analyzed by using the accelerated failure time model (AFT). Results: The median (Q1, Q3) age of 467 Omicron infections including 253 males (54.18%) was 26 (20, 39) years old. There were 132 asymptomatic infections (28.27%) and 335 (71.73%) symptomatic infections. The mean latent period of 467 Omicron infections was 2.65 (95%CI: 2.53-2.78) days, and 98% of infections were positive for nucleic acid test within 6.37 (95%CI: 5.86-6.82) days after infection. The mean incubation period of 335 symptomatic infections was 3.40 (95%CI: 3.25-3.57) days, and 97% of them developed clinical symptoms within 6.80 (95%CI: 6.34-7.22) days after infection. The results of the AFT model analysis showed that compared with the group aged 18-49 years old, the latent period [exp(ß)=1.36 (95%CI: 1.16-1.60), P<0.001] and incubation period [exp(ß)=1.24 (95%CI: 1.07-1.45), P=0.006] of infections aged 0-17 years old were prolonged. The latent period [exp(ß)=1.38 (95%CI: 1.17-1.63), P<0.001] and the incubation period [exp(ß)=1.26 (95%CI: 1.06-1.48), P=0.007] of infections aged 50 years old and above were also prolonged. Conclusion: The latent period and incubation period of most Omicron infections are within 7 days, and age may be a influencing factor of the latent period and incubation period.

[Advances in clinical studies of chronic cough].

Chronic cough is a common complaint in respiratory specialist clinics, with a significant impact on cough-specific quality of life and psychophysiological health. The diagnosis, treatment and management of chronic cough remains a major challenge. We summarized a series of recent advances from clinical studies in the epidemiology, diagnosis and management of chronic cough over the past year.

[Clinical presentation of acute primary angle-closure glaucoma during the 2019-nCoV epidemic of Omicron variants: a single-center retrospective study].

Objective: To investigate the clinical presentation pattern of acute primary angle-closure glaucoma (PACG) during the 2019 novel coronavirus (2019-nCoV) pandemic over the past three years, and its relationship with 2019-nCoV infections of Omicron variants in Guangdong province. Methods: Ecological study.Patients who were newly diagnosed with acute PACG from February 2020 to January 2023 at the Zhongshan Ophthalmic Center of Sun Yat-sen University were included in the study, and their basic information was collected. Patients were divided into the 2020 group (diagnosed between February 1st, 2020 and January 31st 2021), the 2021 group (diagnosed between February 1st, 2021 and January 31st 2022), and the 2022 group (diagnosed between February 1st, 2022 and January 31st 2023). The clinical presentation pattern of newly diagnosed acute PACG was observed and compared between groups. The daily number of newly diagnosed 2019-nCoV infections in Guangdong province was obtained from the Chinese Center for Disease Control and Prevention. The correlation between the daily number of newly diagnosed acute PACG and that of newly diagnosed 2019-nCoV infections during the epidemic period of Omicron variants between December 2022 and January 2023 was assessed. Results: The study included 1 048 patients with newly diagnosed acute PACG, with 235 for the 2020 group, 274 for the 2021 group, and 539 for the 2022 group. Our results showed that the average weekly number of newly diagnosed acute PACG patients in 2022 [8 (5, 11)] was significantly larger than that in 2020 (4.52±1.95, P<0.05) and 2021 (5.27±2.76, P<0.05). The average weekly number increased to 22.11±20.84 between December 2022 and January 2023. The total number of newly diagnosed acute PACG patients during this period was 199, which was 36.9% (199/539) of the total number of the same year and was 6.63 and 6.42 times as many as that in the same period (December and January) of 2020 and 2021. The proportion of patients with bilateral eye involvement during this period in 2022 was significantly higher than that in 2020 and 2021 (P<0.05). Further analysis found that 88.6% (109/123) of cases had a history of 2019-nCoV infection 2 (0, 3) days before the onset of acute PACG symptoms in average. The estimated daily number of acute PACG onset increased rapidly, peaked on December 23th, 2022, and then dropped gradually. This trend was similar to that of the daily number of new 2019-nCoV infections in Guangdong province. Changes of the daily number of new 2019-nCoV infections in Guangdong province had a positive correlation with the estimated daily number of acute PACG onset (r=0.84, P<0.001). Conclusion: A dramatic increase in the clinical presentation of acute PACG was observed at Zhongshan Ophthalmic Center between December 2022 and January 2023, which was the epidemic period of Omicron variants. There is a correlation between the trend of the estimated daily number of acute PACG onset and that of new 2019-nCoV infections of Omicron variants in Guangdong province, but the exact reason remains to be further studied. (This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on August 31, 2023).

Dual-energy x-ray absorptiometry scanner mismatch in follow-up bone mineral density testing.

Scanner mismatch occurs frequently with follow-up dual-energy x-ray absorptiometry (DXA) scans. Nearly one-in-five follow-up DXA scans were conducted on non-cross-calibrated scanners (scanner mismatch) and more than a quarter of patients who had a follow-up DXA scan had experienced scanner mismatch. INTRODUCTION: Detecting significant changes in bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) scanners relies on the least significant change (LSC). Results from two different DXA scanners can only be compared, albeit with decreased sensitivity for change, if the LSC between the two scanners has been directly determined through cross-calibration. Performing follow-up DXA scans on non-cross-calibrated scanners (scanner mismatch) has safety and economic implications. This study aims to determine the proportion of scanner mismatch occurring at a population level. METHODS: All patients who completed at least two DXA scans between 1 April 2009 and 31 December 2018 in the province of Alberta, Canada, were identified using population-based health services databases. Scanner mismatch was defined as a follow-up DXA scan completed on a DXA scanner that differed from and was not cross-calibrated to the previous DXA scanner. Multivariate logistic regression models were used to assess predictive factors that may contribute to scanner mismatch. RESULTS: A total of 264,866 patients with 470,641 follow-up DXA scans were identified. Scanner mismatch occurred in 18.9% of follow-up DXA scans; 28.7% of patients experienced at least one scanner mismatch. Longer duration between scans (OR 1.25, 95% CI 1.24-1.26) and major osteoporotic fracture history before index scan (OR 1.06, 95% CI 1.03-1.08) increased risk of scanner mismatch. Osteoporosis medication use before index scan (OR 0.89; 95% CI 0.88-0.91), recency of follow-up scans (OR 0.98, 95% CI 0.73-0.98), female sex (OR 0.97, 95% CI 0.94-1.00), and age at last scan (OR 0.99, 95% CI 0.99-1.00) were associated with lower risk of scanner mismatch. CONCLUSION: Scanner mismatch is a common problem, occurring in one-in-five follow-up DXA scans and affecting more than a quarter of patients. Interventions to reduce this large proportion of scanner mismatch are necessary.

Subcutaneous administration, higher age and lower renal function are associated with erythrocyte methotrexate accumulation in Crohn's disease: a cross-sectional study.

BACKGROUND: Methotrexate is an immunomodulatory drug for patients with Crohn's disease. Erythrocyte MTX-polyglutamates (MTX-PG1-5) may be used for therapeutic drug monitoring (TDM) as MTX-PG is thought to mediate MTX's efficacy. Information on determinants of the concentration of MTX-PG in patients with Crohn's disease is lacking. We aim to identify clinical and biochemical determinants of the erythrocyte MTX-PG1-5 and MTX-PGtotal concentration in patients with Crohn's disease. METHODS: Adults with Crohn's disease on methotrexate treatment who visited the outpatient clinic of Amsterdam UMC were included. Erythrocyte MTX-PGs were measured by tandem mass spectrometry. RESULTS: Nineteen patients were included, with a median duration of MTX use of 77 months (range 7-202). Twelve patients received MTX monotherapy, whereas 7 patients were on concomitant TNF-α inhibitors. The mean dose of MTX was 15.5 mg (SD ± 2.8) and 12 (63%) patients used subcutaneous MTX. MTX-PG1-5 were successfully measured in 18 patients, showing substantial variability in concentrations of MTX-PGtotal and individual species. The median MTX-PGtotal was 117.1 nmol/L (range 46.4-258.7) with preferential accumulation of MTX-PG3 (43.1 nmol/L, range 15.3-96.1). Patients on subcutaneous compared to oral MTX had higher median MTX-PG(4,5) levels (55 versus 9 nmol/L, p = 0.01). Higher age (ß = 0.71) and lower estimated glomerular filtration rate (ß = - 0.52) were associated with a significantly higher MTX-PGtotal concentration (R2 = 0.60, p = 0.001). CONCLUSION: MTX-PG concentrations display a considerable inter-individual variability. Higher MTX-PG accumulation is associated with subcutaneous administration, higher age, and lower renal function in Crohn's disease patients.

Use of real-time artificial intelligence in detection of abnormal image patterns in standard sonographic reference planes in screening for fetal intracranial malformations.

OBJECTIVES: To develop and validate an artificial intelligence system, the Prenatal ultrasound diagnosis Artificial Intelligence Conduct System (PAICS), to detect different patterns of fetal intracranial abnormality in standard sonographic reference planes for screening for congenital central nervous system (CNS) malformations. METHODS: Neurosonographic images from normal fetuses and fetuses with CNS malformations at 18-40 gestational weeks were retrieved from the databases of two tertiary hospitals in China and assigned randomly (ratio, 8:1:1) to training, fine-tuning and internal validation datasets to develop and evaluate the PAICS. The system was built based on a real-time convolutional neural network (CNN) algorithm, You Only Look Once, version 3 (YOLOv3). An image dataset from a third tertiary hospital was used to further validate, externally, the performance of the PAICS and to compare its performance with that of sonologists with different levels of expertise. Furthermore, a prospective video dataset was employed to evaluate the performance of the PAICS in a real-time scan scenario. The diagnostic accuracy, sensitivity, specificity and area under the receiver-operating-characteristics curve (AUC) were calculated to assess the performance of the PAICS and to compare this with the performance of sonologists with different levels of experience. RESULTS: In total, 43 890 images from 16 297 pregnancies and 169 videos from 166 pregnancies were used to develop and validate the PAICS. The system achieved excellent performance in identifying 10 types of intracranial image pattern, with macro- and microaverage AUCs, respectively, of 0.933 (95% CI, 0.798-1.000) and 0.977 (95% CI, 0.970-0.985) for the internal validation image dataset, 0.902 (95% CI, 0.816-0.989) and 0.898 (95% CI, 0.885-0.911) for the external validation image dataset and 0.969 (95% CI, 0.886-1.000) and 0.981 (95% CI, 0.974-0.988) in the real-time scan setting. The performance of the PAICS was comparable to that of expert sonologists in terms of macro- and microaverage accuracy (P = 0.863 and P = 0.775, respectively), sensitivity (P = 0.883, P = 0.846) and AUC (P = 0.891, P = 0.788), but required significantly less time (0.025 s per image for PAICS vs 4.4 s for experts, P < 0.001). CONCLUSIONS: Both in the image dataset and in the real-time scan setting, the PAICS achieved excellent diagnostic performance for various fetal CNS abnormalities. Its performance was comparable to that of experts, but it required less time. A CNN algorithm can be trained to detect fetal CNS abnormalities. The PAICS has the potential to be an effective and efficient tool in screening for fetal CNS malformations in clinical practice. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Investigation of Product Formation in the O(1D, 3P) + N2O Reactions: Comparison of Experimental and Theoretical Kinetics.

The spin-forbidden and spin-allowed reactions of the excited and ground electronic state O(1D, 3P) + N2O(X1Σ+) systems have been studied theoretically. Quantum calculations at the UCCSD(T)/CBS(T, Q, 5)//CCSD/aug-cc-pVTZ level have located two crossing points, MSX1 and MSX2, with energies of 11.2 and 22.7 kcal mol-1 above O(3P) + N2O, respectively. The second-order P-independent rate constants for the adiabatic and non-adiabatic thermal reactions predicted by adiabatic TST/VTST and non-adiabatic TST, respectively, agree closely with the available literature results. The second-order rate constant, k2a = 9.55 × 10-11 exp(-26.09 kcal mol-1/RT) cm3 molecule-1 s-1, for the O(3P) + N2O → 2NO reaction, contributed by both the dominant MSX2 and the minor TS1-a channels, is in reasonable accord with prior experiments and recommendations, covering the temperature range of 1200-4100 K. The calculated rate constant, k2b = 4.47 × 10-12 exp(-12.9 kcal mol-1/RT) cm3 molecule-1 s-1, for the O(3P) + N2O → N2 + O2(a1Δg) reaction, occurring exclusively via MSX1, is also in good agreement with the combined experimental data measured in a shock tube study at T = 1940-3340 K (ref 16) and the result measured by Fourier transform infrared spectroscopy in the temperature range of 988-1083 K (ref 17). Moreover, the spin-allowed rate constants predicted for the singlet-state reactions, k1a = (7.06-7.46) × 10-11 cm3 molecule-1 s-1 for O(1D) + N2O → 2NO and k1b = (4.36-4.66) × 10-11 cm3 molecule-1 s-1 for O(1D) + N2O → N2 + O2(a1Δg) in the temperature range of 200-350 K, agree quantitatively with the experimentally measured data, while the total rate constant k1 = k1a + k1b was also found to be in excellent accordance with many reported values.

Endolymphatic sac tumour: exploring the role of CT and MRI features in the diagnosis of 22 cases.

AIM: To explore the role of imaging features in the diagnosis of endolymphatic sac tumour (ELST). MATERIALS AND METHODS: Twenty-two patients with ELST confirmed at histopathology were included in this retrospective study. All patients underwent computed tomography (CT) and magnetic resonance imaging (MRI) examinations, including diffusion-weighted imaging (DWI; n=18) and dynamic contrast-enhanced (DCE) MRI (n=3). The imaging features of this series were analysed. RESULTS: All lesions appeared as irregular soft-tissue mass lesions located in the middle and posterior margin of the petrous bone. At CT, the normal vestibular aqueduct structure disappeared. Multiple osteoid tissues were present inside the tumour, and destructive bone changes had a "honeycomb" pattern. Twenty cases were accompanied by the incomplete thin bony peripheral rim along the medial margin. On both T1-weighted imaging (WI) and T2WI, all lesions showed hyperintense, hypointense, and isointense mixed signal intensity. Scattered peripheral hyperintensities were found in all cases on T1WI. The mean apparent diffusion coefficient (ADC) value of 18 lesions was (1.35 ± 0.13) × 10-3 mm2/s, which was similar to that of masseter muscles. On enhanced T1WI, all lesions had significant heterogeneous enhancement, and the vascular flowing-void effect was seen in larger lesions (≥1.5 cm). The time-signal intensity curve (TIC) showed a plateau type in all three cases. CONCLUSIONS: The imaging features of ELST, including its location, bone destruction form, MRI signal intensity, and enhancement pattern, are helpful to improve the diagnostic accuracy of this rare tumour.

Potential impact factors on the enhancement of antibiotic resistance in a lake environment.

There is considerable concern regarding antibiotic resistance in the water environment due to antibiotic residues from anthropogenic origins. The low antibiotic concentration in the water environment may promote the selection of antibiotic resistance. However, it is unclear how environmental factors affect resistance selection. We investigated the proliferation of quinolone-susceptible faecal bacteria (E. coli) exposed to low norfloxacin concentration (ng/L) at variable temperatures, exposure times, and carbon concentrations, simulating the conditions of the water environment. The induction of antibiotic resistance in thirteen E. coli isolates was more likely to occur at 37 °C. However, resistance also occurred at temperatures as low as 25 °C, provided a longer exposure time of 5 days. These results suggest that antibiotic resistance is more likely to be induced in regions where temperatures may reach 25-37 °C, such as tropical regions.

Nonsense mutations in KRT1 caused recessive epidermolytic palmoplantar keratoderma with knuckle pads.

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is characterized by diffuse hyperkeratosis affecting palms and soles with suprabasal epidermolysis or vacuolar degeneration histopathologically. The disorder is caused by heterozygous mutations in KRT9 or KRT1. Dominant-negative mutations in KRT1 could also result in epidermolytic ichthyosis with EPPK, a more severe entity affecting the entire body. OBJECTIVE: To investigate the genetic basis and pathogenesis of two unrelated patients with EPPK and knuckle pads, both of whom were born to consanguineous parents of Chinese origin. METHODS: Next-generation sequencing was applied to the two patients using genomic DNA extracted from peripheral blood. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence (IF) staining and Western blot (WB) were employed to evaluate mRNA and protein expression level. Ultrastructural changes of skin lesion were analysed using transmission electron microscopy. RESULTS: Two novel homozygous mutations, c.457C>T (p.Gln153*) and c.33C>G (p.Tyr11*) in KRT1, were identified in patients 1 and 2 respectively. The nonsense mutations were predicted to result in nonsense-mediated mRNA decay and absence of keratin 1, which was confirmed in the skin lesions from patient 1. Upregulated keratin 2 was detected both in the affected and unaffected skin samples from patient 1, while the protein abundance and distribution pattern of keratin 10 remained unchanged. An aberrant and clumped staining pattern of keratin 9 was noted in the palmar skin of patient 1. CONCLUSIONS: Homozygous 'knockout' mutations in KRT1 resulted in EPPK with knuckle pads rather than epidermolytic ichthyosis. We speculated that sparing of non-acral skin might be due to compensatory effect of keratin 2 upregulation by forming heterodimer with keratin 10.