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INTRODUCTION: Locoregional therapies are a mainstay of treatment for patients with neuroendocrine liver metastases (NELM), yet the optimal transarterial approach remains undefined and recent studies have raised concern over the safety of transarterial chemoembolization (TACE). METHODS: Patients with NELM who underwent TACE or transarterial embolization (TAE) at a single institution between 2000-2022 were retrospectively reviewed. Propensity score matching (PSM) controlling for age, sex, bilateral disease, tumor size, lobar embolization, grade, and extrahepatic disease was utilized to compare short- and long-term outcomes. RESULTS: Among 412 patients with NELM, 329 underwent TACE and 83 TAE. Mean age was 60.7 ± 11.1 years. Patients primarily presented with synchronous (69.2%), bilateral (84.2%), and G1 disease (48.8%) and underwent staged procedures (55.8%). Following PSM, TACE was associated with slightly worse post-procedure laboratory values, but no difference in complications compared to TAE (23.3%vs29.3%, p = 0.247). TACE was associated with improved mean PFS (21.8vs10.7 months, p = 0.002), but no difference in radiographic size, chromogranin level, or median overall survival (50.0 months vs not met, p = 0.833). CONCLUSION: Among patients with NELM, TACE was associated with similar short-term outcomes and improved PFS, but no difference in OS compared to TAE. These findings highlight the need for additional research on the optimal locoregional therapy for NELM.

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POEMS syndrome is a rare plasma cell dysplasia. Its clinical manifestations include polyneuropathy, monoclonal protein, increased extravascular volume load, endocrinopathy, organomegaly and skin changes. The complex and atypical symptoms at presentation make early diagnosis challenging due to multiple system involvement. Peripheral neuropathy, limb numbness, is the most common initial symptom of this disease. However, case reports of increased extravascular volume load are rare. This article collected and analyzed the clinical data of two groups of patients with different initial symptoms (increased extravascular volume load and limb numbness). The clinical characteristics and treatment responses were summarized.

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INTRODUCTION: The progression of ferroptosis has been found to be associated with the onset and progression of many diseases. Disruption of iron homeostasis can lead to ferroptosis. We had previously hypothesized that vitamin D may affect serum calcium levels, which in turn regulates ferroptosis by regulating serum iron levels. However, the relationship between serum calcium level and serum iron level is unclear. The purpose of our study was to explore the relationship between serum calcium level and serum iron level among general population in Taizhou, China. METHODS: In this study, a cross-sectional study was conducted. Serum calcium levels and serum iron levels were determined in our work. Pearson's correlation analysis was used to determine the association between serum calcium level and serum iron level. RESULTS: The results showed that serum iron level was negatively correlated with serum calcium level and age. After controlling for age, sex and marital status, serum iron level was still negatively correlated with serum calcium level. CONCLUSIONS: The results suggest that improving serum calcium levels may be a potential strategy for regulating iron metabolism homeostasis. Whether calcium supplementation can reduce serum iron levels in people with low serum calcium levels needs further investigation.

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Anyons are exotic low-dimensional quasiparticles whose unconventional quantum statistics extend the binary particle division into fermions and bosons. The fractional quantum Hall regime provides a natural host, with the first convincing anyon signatures recently observed through interferometry and cross-correlations of colliding beams. However, the fractional regime is rife with experimental complications, such as an anomalous tunneling density of states, which impede the manipulation of anyons. Here we show experimentally that the canonical integer quantum Hall regime can provide a robust anyon platform. Exploiting the Coulomb interaction between two copropagating quantum Hall channels, an electron injected into one channel splits into two fractional charges behaving as abelian anyons. Their unconventional statistics is revealed by negative cross-correlations between dilute quasiparticle beams. Similarly to fractional quantum Hall observations, we show that the negative signal stems from a time-domain braiding process, here involving the incident fractional quasiparticles and spontaneously generated electron-hole pairs. Beyond the dilute limit, a theoretical understanding is achieved via the edge magnetoplasmon description of interacting integer quantum Hall channels. Our findings establish that, counter-intuitively, the integer quantum Hall regime provides a platform of choice for exploring and manipulating quasiparticles with fractional quantum statistics.

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The Puccinia graminis f. sp. tritici (Pgt) Ug99-emerging virulent races present a major challenge to global wheat production. To meet present and future needs, new sources of resistance must be found. Identification of markers that allow tracking of resistance genes is needed for deployment strategies to combat highly virulent pathogen races. Field evaluation of a DH population located a QTL for stem rust (Sr) resistance, QSr.nc-6D from the breeding line MD01W28-08-11 to the distal region of chromosome arm 6DS where Sr resistance genes Sr42, SrCad, and SrTmp have been identified. A locus for seedling resistance to Pgt race TTKSK was identified in a DH population and an RIL population derived from the cross AGS2000 × LA95135. The resistant cultivar AGS2000 is in the pedigree of MD01W28-08-11 and our results suggest that it is the source of Sr resistance in this breeding line. We exploited published markers and exome capture data to enrich marker density in a 10 Mb region flanking QSr.nc-6D. Our fine mapping in heterozygous inbred families identified three markers co-segregating with resistance and delimited QSr.nc-6D to a 1.3 Mb region. We further exploited information from other genome assemblies and identified collinear regions of 6DS harboring clusters of NLR genes. Evaluation of KASP assays corresponding to our co-segregating SNP suggests that they can be used to track this Sr resistance in breeding programs. However, our results also underscore the challenges posed in identifying genes underlying resistance in such complex regions in the absence of genome sequence from the resistant genotypes.

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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 for 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 propagation dynamics of the quasiparticles remains elusive. In particular, although the nonlinearity of the tunnelling 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 noise to shot noise crossover and observe an agreement with expectations. Measurements are fitted to the predicted finite-temperature expression involving both the scaling dimension of the quasiparticles and their charge12,13, in contrast to previous charge investigations focusing on the high-bias shot-noise regime14. A systematic analysis, repeated on several 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.

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The synthesis of group IV metallocene precatalysts for the polymerization of propylene generally yields two different isomers: The racemic isomer that produces isotactic polypropylene (iPP) and the meso isomer that produces atactic polypropylene (aPP). Due to its poor physical properties, aPP has very limited applications. To avoid obtaining blends of both polymers and thus diminish the mechanical and thermal properties of iPP, the meso metallocene complexes need to be separated from the racemic ones tediously-rendering the metallocene-based polymerization of propylene industrially far less attractive than the Ziegler/Natta process. To overcome this issue, we established an isomerization protocol to convert meso metallocene complexes into their racemic counterparts. This protocol increased the yield of iPP by 400 % while maintaining the polymer's excellent physical properties and was applicable to both hafnocene and zirconocene complexes, as well as different precatalyst activation methods. Through targeted variation of the ligand frameworks, methoxy groups at the indenyl moieties were found to be the structural motifs responsible for an isomerization to take place-this experimental evidence was confirmed by density functional theory calculations. Liquid injection field desorption ionization mass spectrometry, as well as 1H and 29Si nuclear magnetic resonance studies, allowed the proposal of an isomerization mechanism.

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OBJECTIVE: (1) Evaluate the accuracy of computed tomography (CT) scans for localization of liver masses. (2) Assess the agreement between radiologists on localization. (3) Determine if location influences the accuracy of localization and histopathologic diagnosis. (4) Determine what lobar vasculature radiologists found most useful for localization. STUDY DESIGN: Retrospective. ANIMALS: A total of 67 client-owned dogs with a total of 75 hepatic masses. METHODS: Records were reviewed for relevant data. Localization for each hepatic mass was performed by four radiologists (JH, EH, ML, JF) independently. RESULTS: Overall accuracy of mass localization was 217/292 (74.3%) by lobe and 264/300 (88%) by division. Accuracy for the quadrate lobe (11/27, 40.7%) was lower (p < .05) than for the caudate process of the caudate lobe (19/24, 79.2%), left medial lobe (47/64, 73.4%) and left lateral lobe (95/101, 89.6%). Accuracy for the right lateral lobe (17/35, 48.6%) was lower (p < .05) lower than for the left lateral lobe (95/101, 89.6%). Accuracy of localization was 173/192 (90.1%) for masses located in the left division, 37/48 (77.1%) in the central division, and 53/60 (88.3%) for the right division. The agreement (kappa) between radiologists was good (0.61-0.8) to excellent (0.81-1) for division and moderate (0.41-0.6) to good for lobe localization. CONCLUSION: CT localization was more accurate for division than lobe localization of canine hepatic masses. Similarly, radiologists had a better agreement for division than lobe localization. CLINICAL SIGNIFICANCE: This study supports CT as a useful modality for liver mass localization based on division. CT localization to specific lobes should be interpreted with some caution.

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A space-resolved vacuum ultraviolet spectroscopy is employed to measure impurity emission profiles (500-3200 Å) on EAST. This study successfully captures C IV (1548.20 and 1550.77 Å) lines emitted from carbon ions and derives ion temperatures using Doppler broadening and a collision model based on their intensity ratios. Both the emission intensity and ion temperature profiles are determined. However, the calculated results reveal a lower temperature of around 10-20 eV with the collision model, suggesting a potential need for further correction in subsequent calculations. Furthermore, this study explores relative rotation velocities from the Doppler shift, indicating an increase in toroidal rotation velocity with applied neutral beam injection. The measured results exhibit concordance with the charge exchange recombination spectrometer data. Furthermore, during boron powder dropping discharges on EAST, B II (1623.60, 1623.79, 1623.95, 1624.02, 1624.17, and 1624.38 Å) emission lines exhibiting a similar time behavior trend with boron powder injection are identified. Ion temperatures are measured using B II (1362.46 Å) through the Doppler broadening method. These techniques hold significant promise for future impurity analysis at the edge of EAST, providing valuable insights into the behavior of carbon and boron ions.

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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.

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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.

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Objective: To compare the CT image characteristics of pneumoconiosis large shadow and primary lung cancer mass, and analyze the value of CT image characteristics in the differential diagnosis of pneumoconiosis large shadow and primary lung cancer. Methods: In September 2022, 43 patients with stage Ⅲ pneumoconiosis who were hospitalized in Zibo Occupational Disease Prevention Hospital from January 2020 to June 2021 and 52 patients with primary lung cancer who were confirmed by pathology in the Affiliated Hospital of Jining Medical University during the same period were selected as the investigation objects, and the image characteristics of pneumoconiosis large shadow or lung cancer mass and surrounding tissues in the chest CT images of the two groups were compared. Univariate analysis, cluster analysis and cross analysis were used to screen out statistically significant indicators as independent variables, and pneumoconiosis and lung cancer as dependent variables for logistic regression analysis. Results: There were statistically significant differences between large shadow of pneumoconiosis and primary lung cancer mass in single factor CT imaging, such as irregular shape of lesions, CT attenuation value, calcification, cavitation, spiculation, liquefactive necrosis, satellite lesions, adjacent emphysema, short spicules, and pleural thickening (P<0.05). CT value ≥92 HU (abnormal CT attenuation value), calcification, peripheral satellite lesions, pleural thickening, parapunctal emphysema, spines on the lesion margin, irregular lesion morphology were typical features of stage Ⅲ pneumoconiosis, with multiple features of aggregation. The typical features of lung cancer were liquefaction necrosis, round or quasi-round appearance, cavitation and interlobar pleura. A logistic regression model was constructed using satellite lesions, spiculation, pleural thickening, and lesion abnormal CT attenuation value had an R(2) of 0.880 and an accuracy of 95.3% for differentiation. Conclusion: Abnormal CT attenuation value, calcification, peripheral satellite lesions, pleural thickening, spiculation at the edges, liquefaction necrosis, interlobar pleura involvement, and cavitation can distinguish the large shadow of stage Ⅲ pneumoconiosis from lung cancer mass.

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Objective: To explore the corrective effects of a personalized corneal refractive surgery design that retains mild myopia in patients over 40 years old with refractive errors and presbyopia. Methods: A retrospective case series study was conducted, including 60 patients (120 eyes) over 40 years old who underwent corneal refractive surgery at Peking Union Medical College Hospital l from January 2023 to December 2023. The patients were divided into two groups based on their preference: Group A (retained mild myopia) and Group B (fully corrected), with 30 patients (60 eyes) in each group. Preoperative and postoperative visual acuity, subjective refraction, slit-lamp examination, corneal topography, and intraocular pressure were assessed at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months after surgery. The effectiveness and safety indices were calculated based on visual acuity before and after surgery. The National Eye Institute Refractive Quality of Life questionnaire was used to evaluate patient satisfaction and postoperative visual symptoms. Results: There were no significant differences in preoperative uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent (SE), corneal thickness, and intraocular pressure between the two groups (all P>0.05). At the final follow-up, the proportions of eyes with UDVA≥0.8 and≥1.0 were 93.3% (56/60) and 60.0% (36/60) in Group A, and 100% (60/60) and 83.3% (50/60) in Group B, respectively. The SE was significantly different between Group A [(-0.35±0.52) D] and Group B [(-0.07±0.55) D] (P<0.05). Near visual acuity was better in Group A than in Group B (P<0.05). The effectiveness indices were 0.96±0.23 and 0.99±0.12, and the safety indices were 1.02±0.11 and 1.02±0.07 for Groups A and B, respectively. Both groups had high overall satisfaction, but Group A had higher scores for near vision, reading, and computer screen viewing. Conclusion: The personalized corneal refractive surgery design that retains mild myopia provides good corrective effects for patients over 40 years old with refractive errors, improving patient satisfaction and quality of life.

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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.

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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.

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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.

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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.

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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.

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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.