Evolving and Novel Applications of Artificial Intelligence in Thoracic Imaging.

The advent of artificial intelligence (AI) is revolutionizing medicine, particularly radiology. With the development of newer models, AI applications are demonstrating improved performance and versatile utility in the clinical setting. Thoracic imaging is an area of profound interest, given the prevalence of chest imaging and the significant health implications of thoracic diseases. This review aims to highlight the promising applications of AI within thoracic imaging. It examines the role of AI, including its contributions to improving diagnostic evaluation and interpretation, enhancing workflow, and aiding in invasive procedures. Next, it further highlights the current challenges and limitations faced by AI, such as the necessity of 'big data', ethical and legal considerations, and bias in representation. Lastly, it explores the potential directions for the application of AI in thoracic radiology.

[Associations between 4 lipid biomarkers and cardiometabolic multimorbidity development in middle aged and old adults in China].

Objective: To estimate the longitudinal association between serum lipid biomarkers and the development of cardiometabolic multimorbidity (CMM) in middle-aged and old adults (≥45) in China, while examining effect differences among degree of dyslipidemia aggregation and various dyslipidemia combination patterns. Methods: Based on data from the China Health and Retirement Longitudinal Study (2011-2018), logistic regression analysis was used to evaluate the associations of TC, LDL-C, HDL-C, TG (4 forms of dyslipidemias), degree and pattern of dyslipidemia combination with CMM. We also used restricted cubic splines to show the dose-response associations between 4 lipid biomarkers and CMM development. Results: Of the 6 522 participants included, 590 (9.05%) developed CMM. After adjusting for covariates, all 4 forms of dyslipidemias were positively associated with CMM development (high TC: OR=1.33, 95%CI: 1.03-1.71; high LDL-C: OR=1.35, 95%CI: 1.05-1.75; low HDL-C: OR=1.45, 95%CI: 1.19-1.77; high TG: OR=1.50, 95%CI: 1.20-1.88). The U-shaped dose-response relationship between LDL-C and CMM development was observed (P for non-linear =0.022). The odds of CMM increased with the increase of dyslipidemias forms, which was highest in those with ≥3 forms of dyslipidemias (OR=2.02, 95%CI: 1.33-3.06). In various dyslipidemia form combinations, the possibility of CMM development was highest in those with high TC, high LDL-C and low HDL-C (OR=3.54, 95%CI: 1.40-8.67). High TC and high LDL-C were significantly associated with CMM development in people without cardiometabolic diseases. Low HDL-C was positively associated with diabetes and CMM development in participants without cardiometabolic diseases, cardiovascular disease (CVD) followed by diabetes, and diabetes followed by CVD. High TG was positively associated with diabetes and CMM in participants without cardiometabolic diseases, and diabetes followed by CVD. Conclusions: A total of 4 forms of dyslipidemia were all independently associated with CMM development in middle-aged and old adults in China. The dose-response relationship between LDL-C level and CMM development was U-shaped. The aggregation of 4 forms of dyslipidemia were associated with the development of CMM. Low HDL-C and high TG were significantly associated with multiple patterns of cardiometabolic diseases development.

Observation of the scaling dimension of fractional quantum Hall anyons.

Unconventional quasiparticles emerging in the fractional quantum Hall regime1,2 present the challenge of observing their exotic properties unambiguously. Although the fractional charge of quasiparticles has been demonstrated since nearly three decades3-5, the first convincing evidence of their anyonic quantum statistics has only recently been obtained6,7 and, so far, the so-called scaling dimension that determines the quasiparticles' propagation dynamics remains elusive. In particular, while the non-linearity of the tunneling quasiparticle current should reveal their scaling dimension, the measurements fail to match theory, arguably because this observable is not robust to non-universal complications8-12. Here we expose the scaling dimension from the thermal to shot noise crossover, and observe an agreement with expectations. Measurements are fitted to the predicted finite temperature expression involving both the quasiparticles scaling dimension and their charge12,13, in contrast to previous charge investigations focusing on the high bias shot noise regime14. A systematic analysis, repeated on multiple constrictions and experimental conditions, consistently matches the theoretical scaling dimensions for the fractional quasiparticles emerging at filling factors ν =1/3 , 2/5 and 2/3. This establishes a central property of fractional quantum Hall anyons, and demonstrates a powerful and complementary window into exotic quasiparticles.

[Bronchoscopic intervention therapy for pulmonary mucormycosis with main bronchial occlusion: a case report].

Pulmonary mucormycosis is one of the most common types of mucormycosis. Tracheobronchial pulmonary mucormycosis primarily affects the tracheobronchial tree, causing lesions that can invade the airway mucosa and muscular layer, damaging the cartilage. It is characterised by acute onset, rapid progression, and high mortality rate, making clinical treatment challenging. This article reports the diagnosis and treatment of a patient with pulmonary mucormycosis complicated by left main bronchus occlusion. In addition to systemic treatment, which consisted mainly of an intravenous injection of amphotericin B combined with an oral suspension of posaconazole, the patient underwent multiple bronchoscopic interventions, including local infusion of amphotericin B under endoscopy, balloon dilation and silicone stent placement. After four months of comprehensive treatment, the therapeutic effect was satisfactory. This report demonstrates that bronchoscopic intervention therapy plays an important role in the comprehensive treatment of pulmonary mucormycosis, especially in preventing death from the progression to obstructive pneumonia.

[Trends in the distribution of Oncomelania hupensis in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023].

OBJECTIVE: To investigate the changes in distribution of Oncomelania hupensis snails in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023, so as to provide insights into formulation of O. hupensis snail surveillance programs. METHODS: The reports on O. hupensis snail surveillance in Songjiang District, Shanghai Municipality from 2009 to 2023 were collected, and the snail surveillance data in forestlands were extracted. The trends in the proportion of areas with snails in forestlands in total areas with snails, occurrence of frames with living snails and density of living snails were evaluated using a Joinpoint regression model in Songjiang District from 2009 to 2023, and the annual percent change (APC) and average annual percent change (AAPC). RESULTS: A total of 40 sites with snails were found in forestlands in 14 administrative villages of 4 townships, Songjiang District, Shanghai Municipality from 2009 to 2023. A total of 39 065 frames were surveyed for snails in settings covering an area of 609 600 m2, and there were 6 084 frames with snails, covering 151 250 m2 snail habitats. A total of 22 210 snails were captured, with the highest density of 260.00 snails/0.1 m2, and 6 262 snails were dissected, with no Schistosoma japonicum infection identified in snails. The proportion of areas with snails in forestlands in total areas with snails appeared a tendency towards a rise in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023 (APC = AAPC = 24.9%, P > 0.05); however, there were no turning points in the trend curve, with the highest proportion seen in 2009 (53.81%), the lowest in 2011 and 2023 (both 0) and a mean proportion of 24.81%. The occurrence of frames with living snails appeared a tendency towards a rise from 2009 to 2023 (APC = AAPC = 41.5%, P > 0.05); however, there were no turning points in the trend curve, with the highest occurrence in 2009 (53.81%), the lowest in 2011 and 2013 (both 0), and the mean occurrence of 15.57%. In addition, the density of living snails appeared a tendency towards a rise from 2009 to 2023 (APC = AAPC = 55.0%, P > 0.05); however, there were no turning points in the trend curve, with the highest density in 2023 (0.96 snails/0.1 m2), the lowest in 2011 and 2013 (both 0), and a mean density of 0.57 snails/0.1 m2. CONCLUSIONS: The difficulty in O. hupensis snail control and risk of imported snails appeared a tendency towards a rise in forestlands in Songjiang District, Shanghai Municipality over years from 2009 to 2023. Supervision and assessment prior to seedling transplantation and intensified surveillance post-transplantation are recommended to reduce the risk of O. hupensis snail importation and spread.

Quantitative characterization of the effects of fulvestrant alone or in combination with taselisib (PI3Kinase inhibitor) on longitudinal tumor growth in patients with estrogen receptor-positive, HER2-negative, PIK3CA-mutant, advanced or metastatic breast cancer.

PURPOSE: Among cases of breast cancer, estrogen receptor-positive (ER +), PIK3CA-mutant, HER2- advanced breast cancer stands as a particularly complex clinical indication where approximately 40% of ER + /HER2- breast carcinomas present mutations in the PIK3CA gene. A significant hurdle in treating ER + breast cancer lies in surmounting the challenges of endocrine resistance. In the clinical setting, a multifaceted approach is essential for this indication, one that not only explores the effectiveness of individual treatments but also delves into the potential gains in therapeutic outcome from combination therapies. METHODS: In the current study, longitudinal tumor growth inhibition (TGI) models were developed to characterize tumor response over time in postmenopausal women with ER + /HER2- advanced or metastatic breast cancer undergoing treatment with fulvestrant alone or in combination with the PI3K inhibitor, taselisib. Impact of clinically relevant covariates on TGI metrics was assessed to identify patient subsets most likely to benefit from treatment with fulvestrant monotherapy or combination with taselisib. RESULTS: Tumor growth rate constant (Kg) was found to increase with increasing baseline tumor size and in the absence of baseline endocrine sensitivity. Further, Kg decreased in the absence of baseline liver metastases both in fulvestrant monotherapy and combination therapy with taselisib. Overall, additive/potentially synergistic anti-tumor effects were observed in patients treated with the taselisib-fulvestrant combination. CONCLUSION: These results have important implications for understanding the therapeutic impact of combination treatment approaches and individualized responses to these treatments. Finally, this work, emphasizes the importance of model informed drug development for targeted cancer therapy. CLINICAL TRIAL REGISTRATION: NCT02340221 Registered January 16, 2015, NCT01296555 Registered February 14, 2011.

[Epidemiological characteristic of viral encephalitis in children and adolescents in Henan Province, 2012-2023].

Objective: To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023. Methods: The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases. Results: A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years (χ2=5.33,P=0.021; χ2=48.14,P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions: From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.

[18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography and conventional imaging modalities in the diagnosis of diabetic foot osteomyelitis: a meta-analysis.

AIM: This meta-analysis aimed to evaluate the comparative diagnostic efficacy of [18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and conventional imaging, MRI, and white blood cell (WBC) scintigraphy in detecting foot osteomyelitis among diabetic patients. MATERIALS AND METHODS: An exhaustive search was conducted within the PubMed and Embase databases to identify publications available up until February 2024. Studies were included if they evaluated the diagnostic efficacy of [18F]FDG PET or the comparative diagnostic performance between PET and (MRI or WBC scintigraphy). Two researchers independently assessed the quality of the included studies, utilizing the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. RESULTS: Nine retrospective or prospective studies involving 605 patients were included in the meta-analysis. For [18F]FDG PET, the overall sensitivity was 0.83(95% CI: 0.69-0.94), while the overall specificity was 0.92(95% CI: 0.86-0.97). In the head-to-head comparison, no significant difference of sensitivity was found between [18F]FDG PET and MRI (0.72 vs. 0.68, P=0.81), as well as between [18F]FDG PET and WBC scintigraphy (0.57 vs. 0.66, P=0.64). In addition, specificity was also found to be no significant difference between [18F]FDG PET and MRI (0.90 vs. 0.82, P=0.27), as well as [18F]FDG PET and WBC scintigraphy (0.81 vs. 0.93, P=0.09). CONCLUSION: [18F]FDG PET demonstrates similar sensitivity and specificity to MRI and WBC scintigraphy in detecting foot osteomyelitis among diabetic patients. MRI, often cited as a primary choice in guidelines, might be preferred due to its lower cost and lower dose. Further larger sample prospective studies are needed to confirm these findings.

The Effect of Exposure to Neighborhood Violence on Glucocorticoid Receptor Signaling in Lung Tumors.

Despite lower rates and intensity of smoking, Black men experience a higher incidence of lung cancer compared to white men. The racial disparity in lung cancer is particularly pronounced in Chicago, a highly segregated urban city. Neighborhood conditions, particularly social stress, may play a role in lung tumorigenesis. Preliminary studies indicate that Black men residing in neighborhoods with higher rates of violent crime have significantly higher levels of hair cortisol, an indicator of stress response. To examine the relationship between social stress exposure and gene expression in lung tumors, we investigated glucocorticoid receptor (GR) binding in 15 lung tumor samples in relation to GR target gene expression levels and zip code level residential violent crime rates. Spatial transcriptomics and a version of ChIP sequencing known as CUT&RUN were used. Heatmap of genes, pathway analysis, and motif analysis were conducted at the statistical significance of P < 0.05. GR recruitment to chromatin was correlated with zip code level residential violent crime rate and overall GR binding increased with higher violent crime rates. Our findings suggest that exposure to residential violent crime may influence tumor biology via reprogramming GR recruitment. Prioritizing lung cancer screening in neighborhoods with increased social stress, such as high levels of violent crime, may reduce racial disparities in lung cancer. SIGNIFICANCE: Exposure to neighborhood violent crime is correlated with glucocorticoid signaling and lung tumor gene expression changes associated with increased tumor aggressiveness, suggesting social conditions have downstream biophysical consequences that contribute to lung cancer disparities.

[Molecular mechanism analysis of a family with hereditary coagulation F â ª deficiency caused by compound heterozygous mutations].

A 34 year old female patient was scheduled to undergo surgical resection due to a "breast nodule". Preoperative examination revealed an activated partial thromboplastin time (APTT) of 66.2 seconds, coagulation factor Ⅺ activity (FⅪ: C) of 2%, and FⅪ antigen (FⅪ: Ag) of 40.3%. The patient and family members showed no abnormal bleeding symptoms. Diagnosed as hereditary coagulation factor Ⅺ deficiency. Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10, c.1107C>A (p.Tyr351stop), and a heterozygous missense mutation in exon 13, c.1562A>G (p.Tyr503Cys). The father and son were p Heterozygous carriers of Tyr351stop mutation, while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations. The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene, while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene, but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.

Design and development of the DE-SPECT system: a clinical SPECT system for broadband multi-isotope imaging of peripheral vascular disease.

Objective. Peripheral Vascular Disease (PVD) affects more than 230 million people worldwide and is one of the leading causes of disability among people over age 60. Nowadays, PVD remains largely underdiagnosed and undertreated, and requires the development of tailored diagnostic approaches. We present the full design of the Dynamic Extremity SPECT (DE-SPECT) system, the first organ-dedicated SPECT system for lower extremity imaging, based on 1 cm thick Cadmium Zinc Telluride (CZT) spectrometers and a dynamic dual field-of-view (FOV) synthetic compound-eye (SCE) collimator.Approach. The proposed DE-SPECT detection system consists of 48 1 cm thick 3D-position-sensitive CZT spectrometers arranged in a partial ring of 59 cm in diameter in a checkerboard pattern. The detection system is coupled with a compact dynamic SCE collimator that allows the user to select between two different FOVs at any time during an imaging study: a wide-FOV (28 cm diameter) configuration for dual-leg or scout imaging or a high-resolution and high-sensitivity (HR-HS) FOV (16 cm diameter) for single-leg or focused imaging.Main results.The preliminary experimental data show that the CZT spectrometer achieves a 3D intrinsic spatial resolution of <0.75 mm FWHM and an excellent energy resolution over a broad energy range (2.6 keV FWHM at 218, 3.3 keV at 440 keV). From simulations, the wide-FOV configuration offers a 0.034% averaged sensitivity at 140 keV and <8 mm spatial resolution, whereas the HR-HS configuration presents a peak central sensitivity of 0.07% at 140 keV and a ∼5 mm spatial resolution. The dynamic SCE collimator enables the capability to perform joint reconstructions that would ensure an overall improvement in imaging performance.Significance. The DE-SPECT system is a stationary and high-performance SPECT system that offers an excellent spectroscopic performance with a unique computer-controlled dual-FOV imaging capability, and a relatively high sensitivity for multi-tracer and multi-functional SPECT imaging of the extremities.

[Prognostic value of skeletal muscle measured by CT at the T4 level in advanced EGFR-positive non-small cell lung cancer patients treated with ecotinib].

Objective: To investigate the prognostic value of skeletal muscle measured by CT at the level of the fourth thoracic vertebra (T4) in advanced epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients treated with ecotinib. Methods: The study retrospectively reviewed clinical and pathological characteristics of 176 patients with advanced EGFR-positive NSCLC who received ecotinib and underwent chest CT scans at Wuhan Union Hospital between January 2017 and October 2020. Among them, 70 were male and 106 were female, with ages ranging from 27 to 80 (58.6±10.6) years. As of August 21, 2021, the median follow-up duration was 19.2 months (95%CI: 15.3 to 23.7 months). The optimal cut-off value of skeletal muscle density (T4-SMD) on CT images at the T4 level were determined using X-tile software. Kaplan-Meier analysis and log-rank test were used to plot progression-free survival curves. Cox proportional hazards regression models were employed to analyze factors influencing 1-year progression-free survival (PFS), and a nomogram prognostic model was constructed accordingly. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were utilized to evaluate the predictive value of the nomogram. Results: The T4-SMD [M (Q1,Q3)] of 176 patients was 42.56 (37.05, 45.93) HU. Patients were divided into low T4-SMD group (n=122) and high T4-SMD group (n=54) based on the cut-off value (The values for males and females were 49.44 and 41.41 HU, respectively) of T4-SMD. The median PFS time and 1-year PFS rate in the low T4-SMD group were significantly lower than those in the high T4-SMD group [10.4 (95%CI: 9.3-11.8) vs 13.7 (95%CI: 11.1-18.5) months, 36.1% vs 59.3%, respectively, P=0.034]. Eastern Cooperative Oncology Group performance status (HR=3.308, 95%CI: 1.183-9.247, P=0.023), lactate dehydrogenase level (HR=1.852, 95%CI: 1.037-3.307, P=0.037), systemic immune-inflammation index (HR=1.772, 95%CI: 1.019-3.080, P=0.043), and T4-SMD (HR=0.563, 95%CI: 0.325-0.974, P=0.040) were prognostic factors for 1-year PFS in advanced EGFR-positive NSCLC patients treated with ecotinib. A nomogram for predicting 1-year PFS of advanced EGFR-positive NSCLC patients treated with ecotinib was constructed based on the four indicators selected by multivariate Cox regression analysis. The area under the ROC curve of the nomogram was 0.775 (95%CI: 0.676-0.874). The calibration curve showed good consistency between the predicted and actual 1-year PFS. DCA demonstrated good clinical prediction effectiveness of the nomogram. Conclusion: Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.

Age- and Sex-Dependent Effects of Moderate Exercise on Endogenous Pain Inhibition in Rats.

Diffuse noxious inhibitory controls (DNICs), or the pain inhibits pain phenomenon, refer to reduced pain-like behaviors that are displayed following a noxious conditioning stimulus located far from the test stimulus and have also been referred to as "descending control of nociception" when measured in awake-behaving animals. In this study, we sought to determine the impact of moderate long-term exercise on the DCN response and determine if this effect differed across age and sex. After a six-week exercise program consisting of 30 min of moderate treadmill running 5 days a week, the animals' forepaws were injected with capsaicin, and DCN responses were assessed using thermal withdrawal latencies of the hind paw. Young, exercised male and female rats displayed prolonged DCN responses relative to their sedentary counterparts, with the young exercised male group displaying longer-lasting DCN facilitation than the young exercised females. Exercise did not impact DCN responses in either male or female aged rats. Additionally, the serum testosterone levels did not change following exercise in any group. Importantly, the levels of corticosterone did not change following the exercise program, indicating that changes in the DCN response are not due to stress-induced analgesia. Our findings suggest that moderate exercise can facilitate the DCN response in young animals, even when this exercise does not change the levels of serum testosterone.

[Innovation and development of surgical techniques for pancreatic tumors].

In recent years, great progress has been made in the diagnosis and treatment of pancreatic tumors. In terms of diagnosis, three-dimensional CT reconstruction, PET-CT scan, endoscopic ultrasound with needle biopsy are used to evaluate the benign or malignant stage and biological characteristics of the tumor, to make treatment decisions more scientific and reasonable. In terms of treatment, new technologies, such as arterial priority arterial sheath dissection and radical resection of the retroperitoneal lipo-lymphatic layer, have continuously emerged to improve radical curability of tumors. For benign or low-grade malignant pancreatic tumors, function-preserving surgery is adopted to avoid long-term complications. Minimally invasive pancreatic surgery has advanced in leaps and bounds. Both standard radical surgery and function-preserve surgery can be performed under a laparoscope or robot. Non-surgical treatment has developed quickly with each passing day; for locally advanced or metastatic pancreatic cancer, neoadjuvant therapy is expected to be down-staged or transformed into surgery. These advances in diagnosis and treatment technology have led to multidisciplinary teamwork. Based on accurate assessment, giving full play to the advantages of laparoscopic and robotic systems in diagnosis and treatment, attaching importance to comprehensive nonsurgical treatment and doctor-patient communication with care throughout the process, these are keys to improve the clinical efficacy of pancreatic tumors in the era of minimally invasive surgery.

[Clinical features and follow-up study on 55 patients with adolescence-onset methylmalonic acidemia].

Objective: To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies. Methods: This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months. Results: Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work. Conclusions: Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Retrospective Assessment of Translational Pharmacokinetic-Pharmacodynamic Modeling Performance: A Case Study with Apitolisib, a Dual PI3K/mTOR Inhibitor.

BACKGROUND AND OBJECTIVES: Despite significant progress in biomedical research, the rate of success in oncology drug development remains inferior to that of other therapeutic fields. Mechanistic models provide comprehensive understanding of the therapeutic effects of drugs, which is crucial for designing effective clinical trials. This study was performed to acquire a better understanding of PI3K-AKT-TOR pathway modulation and preclinical to clinical translational bridging for a specific compound, apitolisib (PI3K/mTOR inhibitor), by developing integrated mechanistic models. METHODS: Integrated pharmacokinetic (PK)-pharmacodynamic (PD)-efficacy models were developed for xenografts bearing human renal cell adenocarcinoma and for patients with solid tumors (phase 1 studies) to characterize relationships between exposure of apitolisib, modulation of the phosphorylated Akt (pAkt) biomarker triggered by inhibition of the PI3K-AKT-mTOR pathway, and tumor response. RESULTS: Both clinical and preclinical integrated models show a steep sigmoid curve linking pAkt inhibition to tumor growth inhibition and quantified that a minimum of 35-45% pAkt modulation is required for tumor shrinkage in patients, based on platelet-rich plasma surrogate matrix and in xenografts based on tumor tissue matrix. Based on this relationship between targeted pAkt modulation and tumor shrinkage rate, it appeared that a constant pAkt inhibition of 61% and 65%, respectively, would be necessary to achieve tumor stasis in xenografts and patients. CONCLUSIONS: These results help when it comes to evaluating the translatability of the preclinical analysis to the clinical target, and provide information that will enhance the value of future preclinical translational dose-finding and dose-optimization studies to accelerate clinical drug development. TRIAL REGISTRY: ClinicalTrials.gov NCT00854152 and NCT00854126.

Global Burden of Alzheimer's Disease and Other Dementias Attributed to High Fasting Plasma Glucose from 1990 to 2019.

BACKGROUND: Burden of Alzheimer's disease (AD) and other dementias have grown rapidly over the decades, and high fasting plasma glucose (HFPG) was one of the well-established risk factors. It is urgently needed to estimate the global burden of AD and other dementias attributable to high fasting plasma glucose between regions, countries, age groups, and sexes to inform development of effective primary disease prevention strategies and intervention policies. METHODS: The burden of AD and other dementias attributable to HFPG was estimated based on a modeling strategy using the Global Burden of Disease Study 2019 dataset. The disease burden and time trend globally and by region, country, development level, age group, and sex were evaluated. RESULTS: The number of AD and other dementias-related deaths attributable to HFPG increased from 42,998.23 (95% uncertainty interval, UI: 4459.86-163,455.78, the year of 1990) to 159,244.53 deaths (95% UI 18,385.23-583,514.15, the year of 2019). The age-standardized death rate increased from 1.69 (95% UI 0.18-6.54) in 1990 to 2.24 (95% UI 0.26-8.24) in 2019. The burden was higher in more developed regions. The burden in women was double that in men, that HFPG-attributable AD and other dementias caused 99,812.79 deaths (95% UI 9005.67-387,160.60) in women and 59,431.74 deaths (95% UI 5439.02-214,819.23) in men, with age-standardized death rate of 2.27 (95% UI 0.20-8.79) per 100,000 population in women and 2.20 (95% UI 0.20-8.00) in men. CONCLUSION: Findings from the current study emphasizes the urgent requirement for targeted interventions in high-development regions, as well as the importance of proactive measures in middle-development countries in protection of AD and other dementias. The gender disparity necessitates the integration of gender-specific considerations in targeted approaches in prevention of AD and other dementias.

[Opportunities and challenges in accurate early diagnosis and treatment of lung cancer/pulmonary nodules].

Lung cancer remains the most prevalent and lethal malignancy in our country. Early diagnosis and treatment are crucial for improving patient prognosis in lung cancer/pulmonary nodules. Recent advancements in non-invasive/minimally invasive liquid biopsy, multi-omics, and artificial intelligence technologies have significantly enhanced the accuracy of early lung cancer/pulmonary nodule diagnosis. However, an early diagnostic method with both high sensitivity and specificity is yet to be established. Furthermore, addressing the methods and extent of early precision surgery, local precision therapy, perioperative combined treatment, and postoperative recurrence and metastasis monitoring are urgent challenges in the early management of lung cancer/pulmonary nodules. Integrating the advantages of various treatment strategies and formulating personalized and precise treatment plans is key to further improving patient survival. In the future, while exploring new therapeutic strategies, it is necessary to continuously search for biomarkers to identify the population that will benefit from the treatment effectively. Additionally, large-sample randomized controlled clinical studies should be conducted to investigate the benefits of long-term patient survival under a diverse range of treatment strategies.