Circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers combined with clinicopathological risk has potential to better predict recurrence in stage III breast cancer treated with neoadjuvant chemotherapy: a pilot study.

BACKGROUND: The potential value of detecting epithelial-mesenchymal transition (EMT) CTCs in early breast cancer, especially during the neoadjuvant therapy period, requires further investigation. We analyzed dynamic CTC phenotype status, to improve recurrence risk stratification for patients with stage III breast cancers. METHODS: We enrolled 45 patients with stage III breast cancers from 2 clinical trials undergoing neoadjuvant chemotherapy and utilized the CanPatrol CTC enrichment technique pre- and post-chemotherapy to identify CTC phenotypes, including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs, in peripheral blood samples. Kaplan-Meier analyses were conducted to explore the prognostic value of dynamic change of CTC count and the proportion of CTCs with different phenotypes. Then, redefine the risk stratification based on CTC status and clinicopathological risk in combination. RESULTS: Increased proportion of M + CTCs was a high-risk CTC status that was associated with decreased DFS (HR, 3.584; 95% CI, 1.057-12.15). In a combined analysis with clinicopathological risk, patients with high-risk tumors had an elevated risk of recurrence compared to patients with low-risk tumors (HR, 4.482; 95% CI, 1.246-16.12). The recurrence risk could be effectively stratified by newly defined risk stratification criteria, with 5-year DFS of 100.0%, 77.3%, and 50.0%, respectively, for low-risk, mid-risk, and high-risk patients (P = 0.0077). Finally, in the ROC analysis, the redefined risk stratification demonstrated higher predictive significance with an AUC of 0.7727, compared to CTC status alone (AUC of 0.6751) or clinicopathological risk alone (AUC of 0.6858). CONCLUSION: The proportion of M + CTCs increased after neoadjuvant chemotherapy indicating a higher risk of tumor recurrence. Combining CTC status with clinicopathological risk has potential to redefine the risk stratification of stage III breast cancers and provide improved predictions of relapse.

Dietary Amino Acids Promote Glucagon-like Hormone Release to Generate Novel Calcium Waves in Adipose Tissues.

Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various obesity-related morbidities. Among different metabolic regulatory signals, cytosolic Ca2+ plays pivotal roles in metabolic regulation, including glycolysis, gluconeogenesis, and lipolysis. Recently, intercellular calcium waves (ICWs), the propagation of Ca2+ signaling through tissues, have been found in different systems to coordinate multicellular responses. Nevertheless, our understanding of how ICWs are modulated and operate within living organisms remains limited. In this study, we explore the real-time dynamics, both in organ culture and free-behaving animals, of ICWs in Drosophila larval and adult adipose tissues. We identified Adipokinetic hormone (AKH), the fly functional homolog of mammalian glucagon, as the key factor driving Ca2+ activities in adipose tissue. Interestingly, we found that AKH, which is released in a pulsatile manner into the circulating hemolymph from the AKH-producing neurosecretory cells (APCs) in the brain, stimulates ICWs in the larval fat by a previously unrecognized gap-junction-independent mechanism to promote lipolysis. In the adult fat body, however, gap-junction-dependent random ICWs are triggered by a presumably uniformly diffused AKH. This highlights the stage-specific interplay of hormone secretion, extracellular diffusion, and intercellular communication in the regulation of Ca2+ dynamics. Additionally, we discovered that specific dietary amino acids activate the APCs, leading to increased intracellular Ca2+ and subsequent AKH secretion. Altogether, our findings identify that dietary amino acids regulate the release of AKH peptides from the APCs, which subsequently stimulates novel gap-junction-independent ICWs in adipose tissues, thereby enhancing lipid metabolism.

Multicolour and lineage-specific interphase chromosome Flow-FISH: method development and clinical validation.

Flow cytometry can be applied in the detection of fluorescence in situ hybridisation (FISH) signals to efficiently analyse chromosomal aberrations. However, such interphase chromosome (IC) Flow-FISH protocols are currently limited to detecting a single colour. Furthermore, combining IC Flow-FISH with conventional multicolour flow cytometry is difficult because the DNA-denaturation step in FISH assay also disrupts cellular integrity and protein structures, precluding subsequent antigen-antibody binding and hindering concurrent labeling of surface antigens and FISH signals. We developed a working protocol for concurrent multicolour flow cytometry detection of nuclear IC FISH signals and cell surface markers. The protocol was validated by assaying sex chromosome content of blood cells, which was indicative of chimerism status in patients who had received sex-mismatched allogeneic haematopoietic stem cell transplants (allo-HSCT). The method was also adapted to detect trisomy 12 in chronic lymphocytic leukaemia (CLL) subjects. We first demonstrated the feasibility of this protocol in detecting multiple colours and concurrent nuclear and surface signals with high agreement. In clinical validation experiments, chimerism status was identified in clinical samples (n=56) using the optimised IC Flow-FISH method; the results tightly corresponded to those of conventional slide-based FISH (R2=0.9649 for XX cells and 0.9786 for XY cells). In samples from patients who received sex-mismatched allo-HSCT, individual chimeric statuses in different lineages could be clearly distinguished with high flexibility in gating strategies. Furthermore, in CLL samples with trisomy 12, this method could demonstrate that enriched trisomy 12 FISH signal was present in B cells rather than in T cells. Finally, by performing combined labelling of chromosome 12, X chromosome, and surface markers, we could detect rare residual recipient CLL cells with trisomy 12 after allo-HSCT. This adaptable protocol for multicolour and lineage-specific IC Flow-FISH advances the technique to allow for its potential application in various clinical contexts where conventional FISH assays are currently being utilised.

PLA tissue-engineered scaffolds loaded with sustained-release active substance chitosan nanoparticles: Modeling BSA-bFGF as the active substance.

The utilization of basic fibroblast growth factor (bFGF) in the development of tissue-engineered scaffolds is both challenging and imperative. In our pursuit of creating a scaffold that aligns with the natural healing process, we initially fabricated chitosan-bFGF nanoparticles (CS-bFGF NPs) through electrostatic spraying. Subsequently, polylactic acid (PLA) fiber was prepared using electrospinning technique, and the CS-bFGF NPs were uniformly embedded within the pores of porous PLA fibers. Scanning electron micrographs illustrate the smooth surface of the nanoparticles, showing a porous structure intricately attached to PLA fibers. Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) analyses provided conclusive evidence that the CS-bFGF NPs were uniformly distributed throughout the porous PLA fibers, forming a robust physical bond through electrostatic adsorption. The resultant scaffolds exhibited commendable mechanical properties and hydrophilicity, facilitating a sustained-release for 72 h. Furthermore, the biocompatibility and degradation performance of the scaffolds were substantiated by monitoring conductivity and pH changes in pure water over different time intervals, complemented by scanning electron microscopy (SEM) observations. Cell experiments confirmed the cytocompatibility of the scaffolds. In animal studies, the group treated with 16 % NPs/Scaffold demonstrated the highest epidermal reconstruction rate. In summary, our developed materials present a promising candidate for serving as a tissue engineering scaffold, showcasing exceptional biocompatibility, sustained-release characteristics, and substantial potential for promoting epidermal regeneration.

Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Non-Squamous EGFR-Wildtype NSCLC in the Phase 2 LUMINOSITY Trial.

PURPOSE: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase 2 LUMINOSITY trial (NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage 1) and expand the selected group for efficacy evaluation (stage 2). Stage 2 enrolled patients with non-squamous epidermal growth factor receptor (EGFR)-wildtype NSCLC. METHODS: Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 prior lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in non-squamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg every 2 weeks. Primary endpoint was overall response rate (ORR) by independent central review. RESULTS: In total, 172 patients with non-squamous EGFR-wildtype NSCLC received Teliso-V in stages 1 and 2. ORR was 28.6% (95% CI, 21.7-36.2; c-Met high, 34.6% [24.2-46.2]; c-Met intermediate, 22.9% [14.4-33.4]). Median duration of response was 8.3 months (95% CI, 5.6-11.3; c-Met high, 9.0 [4.2-13.0]; c-Met intermediate: 7.2 [5.3-11.5]). Median overall survival was 14.5 months (95% CI, 9.9-16.6; c-Met high, 14.6 [9.2-25.6]; c-Met intermediate, 14.2 [9.6-16.6]). Median progression-free survival was 5.7 months (95% CI, 4.6-6.9; c-Met high, 5.5 [4.1-8.3]; c-Met intermediate: 6.0 [4.5-8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 was peripheral sensory neuropathy (7%). CONCLUSION: Teliso-V was associated with durable responses in c-Met protein-overexpressing non-squamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.

Design, Synthesis, and Insecticidal Activity of Pyridino[1,2-a]pyrimidines Containing Indole Moeites at the 1-Position.

Research on mesoionic structures in pesticide design has gained significant attention in recent years. However, the 1-position of pyridino[1,2-a]pyrimidine is usually designed with 2-chlorothiazole, 2-chloropyridine, or cyano moieties commonly found in neonicotinoid insecticides. In order to enrich the available pharmacophore library, here, we disclose a series of new pyridino[1,2-a]pyrimidine mesoionics bearing indole-containing substituents at the 1-position. Most of these target compounds are confirmed to have good insecticidal activity against aphids through bioevaluation. In addition, a three-dimensional structure-activity relationship model is established to allow access to optimal compound F45 with an LC50 value of 2.97 mg/L. This value is comparable to the property achieved by the positive control triflumezopyrim (LC50 = 2.94 mg/L). Proteomics and molecular docking analysis suggest that compound F45 has the potential to modulate the functioning of the aphid nervous system through its interaction with neuronal nicotinic acetylcholine receptors. This study expands the existing pharmacophore library for the future development of new mesoionic insecticides based on 1-position modifications of the pyridino[1,2-a]pyrimidine scaffold.

Revealing potential Rab proteins participate in regulation of secretory autophagy machinery.

Autophagy can be classified as degradative and secretory based on distinct functions. The small GTPase proteins Rab8a and Rab37 are responsible for secretory autophagy-mediated exocytosis of IL-1ß, insulin, and TIMP1 (tissue inhibitor of 54 metalloproteinase 1). Other Rab family members participating in secretory autophagy are poorly understood. Herein, we identified 26 overlapped Rab proteins in purified autophagosomes of mouse pancreatic ß-cell "Min-6" and human lung cancer cell "CL1-5-Q89L" with high secretory autophagy tendency by LC-MS/MS proteomics analysis. Six Rab proteins (Rab8a, Rab11b, Rab27a, Rab35, Rab37, and Rab7a) were detected in autophagosomes of four cell lines, associating them with autophagy-related vesicle trafficking. We used CL1-5-Q89L cell line model to evaluate the levels of Rab proteins colocalization with autophagy LC3 proteins and presence in purified autophagosomes. We found five Rab proteins (Rab8a, Rab11b, Rab27a, Rab35, and Rab37) are highly expressed in the autophagosome compared to the normal control by immunoblotting under active secretion conditions. However, only Rab8a, Rab35, and Rab37 showing high colocalization with LC3 protein by cofocal microscopy. Despite the discrepancy between the image and immunoblotting analysis, our data sustains the speculation that Rab8a, Rab11b, Rab27a, Rab35, and Rab37 are possibly associated with the secretory autophagy machinery. In contrast, Rab7a shows low colocalization with LC3 puncta and low level in the autophagosome, suggesting it regulates different vesicle trafficking machineries. Our findings open a new direction toward exploring the role of Rab proteins in secretory autophagy-related cargo exocytosis and identifying the cargoes and effectors regulated by specific Rab proteins.

Signal-averaged electrocardiography as a noninvasive tool for evaluating the ventricular substrate in patients with nonischemic cardiomyopathy: reassessment of an old tool.

Introduction: Signal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM. Methods and results: This retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence. Conclusion: In our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

A quinoline derivative-based supramolecular gel for fluorescence 'turn-off' detection of Fe3+and Cu2.

In this research, we synthesized and constructed a novel gelator (namedQN) combining quinoline and naphthalene that self-assembled in N, N-dimethylformamide (DMF) to form a stable supramolecular gel (namedOQN). Under UV light, gelOQNexhibited extremely bright yellow fluorescence. The gelOQNshowed excellent sensing performance for both Fe3+and Cu2+, with a fluorescence 'turn-off' detection mechanism and the lowest detection limit of 7.58 × 10-8M and 1.51 × 10-8M, respectively. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectra, x-ray powder diffraction (XRD), rheological measurements, x-ray photoelectron spectroscopy (XPS), and fluorescence spectroscopy were used to characterize the gelOQN. TheOQNion-responsive membrane created is an excellent fluorescent writing material.

Leadership training effectiveness for high-performing young nurses in a teaching hospital - A quasi-experimental study.

BACKGROUND: Good nursing leadership management positively correlates with patient care quality and an organization's performance. Plans to nurture top-notch talents and strengthen management functions are essential to retain key talents and achieve sustainability. The leadership training for nursing staff should begin early to cope with complex clinical situations. OBJECTIVES: To compare the impact of leadership training on high-performing young nurses' (young nursing elite) management functions and team behavior. SETTING: A public teaching hospital in Taipei, Taiwan. METHODS: This research implemented a longitudinal quasi-experimental study with a fixed time series design; the target subjects were youth nursing elites who received training, along with their direct managers and peers, for a total of 102 participants. The training course intervention included the classroom teaching of leadership management functions, arranging internships in the hospital's internal administrative units and professional nursing institutions, and the direct managers sharing their experiences during teaching. We measured the outcome indicators before the course intervention, at the end of the course intervention, and three months after using the management function and team behavior scales. RESULTS: The mean score of the direct managers' assessments regarding the youth nursing elite's pre-test team behavior was 4.18. This improved by 0.68 points (p < .001) after the program intervention and improved by 0.65 points (p < .001) three months after the program compared to the pre-test. There was no statistically significant difference between the two groups as analyzed using GEE. The mean score of the pre-test self-assessment management function of the young nursing elite was 3.27. This improved by 1.06 points (p < .001) after the program intervention and by 1.14 points (p < .001) three months after the program compared to the pre-test. There was no statistically significant difference between the three groups using GEE analysis. CONCLUSIONS: Leadership training enhances young nursing professionals' leadership function and team behavior.

Nitazoxanide protects against experimental ulcerative colitis through improving intestinal barrier and inhibiting inflammation.

Ulcerative colitis is a chronic disease with colonic mucosa injury. Nitazoxanide is an antiprotozoal drug in clinic. Nitazoxanide and its metabolite tizoxanide have been demonstrated to activate AMPK and inhibit inflammation, therefore, the aim of the present study is to investigate the effect of nitazoxanide on dextran sulfate sodium (DSS)-induced colitis and the underlying mechanism. Oral administration of nitazoxanide ameliorated the symptoms of mice with DSS-induced colitis, as evidenced by improving the increased disease activity index (DAI), the decreased body weight, and the shortened colon length. Oral administration of nitazoxanide ameliorated DSS-induced intestinal barrier dysfunction and reduced IL-6 and IL-17 expression in colon tissues. Mechanistically, nitazoxanide and its metabolite tizoxanide treatment activated AMPK and inhibited JAK2/STAT3 signals. Nitazoxanide and tizoxanide treatment increased caudal type homeobox 2 (CDX2) expression, increased alkaline phosphatase (ALP) activity and promoted tight junctions in Caco-2 cells. Nitazoxanide and tizoxanide treatment restored the decreased zonula occludens-1(ZO-1) and occludin protein levels induced by LPS or IL-6 in Caco-2 cells. On the other hand, nitazoxanide and tizoxanide regulated macrophage bias toward M2 polarization, as evidenced by the increased arginase-1expression in bone marrow-derived macrophages (BMDM). Nitazoxanide and tizoxanide reduced the increased IL-6, iNOS and CCL2 pro-inflammatory gene expressions and inhibited JAK2/STAT3 activation in BMDM induced by LPS. In conclusion, nitazoxanide protects against DSS-induced ulcerative colitis in mice through improving intestinal barrier and inhibiting inflammation and the underlying mechanism involves AMPK activation and JAK2/STAT3 inhibition.

Complete response to front-line therapies is associated with long-term survival in HIV-related lymphomas in Taiwan.

BACKGROUND: The prognosis for people living with HIV (PLWH) who develop lymphomas has been greatly improved by combination antiretroviral therapy (cART) and anti-CD20 monoclonal antibodies. However, real-world clinical data on this patient group in Asia are limited. METHODS: Treatment outcomes were retrospectively examined for 104 PLWH with lymphomas between 2000 and 2019. The cohort comprised five PLWH with Hodgkin lymphoma (HL) and 99 with non-Hodgkin lymphomas, including 61 with diffuse large B-cell lymphoma (DLBCL), 19 with Burkitt lymphoma (BL), nine with primary central nervous system lymphoma (PCNSL) and ten with other subtypes. RESULTS: The 5-year overall survival (OS) rates were as follows: HL (100%), PCNSL (76.2%), other subtypes (60.0%), BL (57.4%), and DLBCL (55.6%). Individuals who achieved complete response (CR) to front-line therapies had a significantly better 5-year OS rate than those without (96.2% vs. 17.8%, p < 0.001). PLWH who received cART for ≤6 months had significantly lower CD4+ T-cell counts at lymphoma diagnosis than those who received cART for longer periods (p = 0.048). Additionally, the 5-year OS rate was better for PLWH who received cART for ≤6 months before lymphomas diagnosis than those who received cART for longer periods (64.5% vs. 51.9%, p = 0.114). CONCLUSIONS: PLWH with DLBCL or BL had OS rates compatible to patients without HIV infection. Better outcomes for patients achieving CR to front-line therapy and those with shorter cART duration before lymphoma diagnosis suggest an underlying biological distinction in the lymphomas and the involvement of immunity, which warrants further studies.

Adiposity indices and their higher predictive value for new-onset hypertension in metabolically healthy young women: findings from a population-based prospective cohort study.

BACKGROUND AND AIMS: The present study aimed to investigate the predictive ability of selected adiposity indices, such as body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and waist-to-height ratio (WHtR), for new-onset hypertension in metabolically healthy Taiwanese adults. The study also sought to establish sex-specific cutoff points for these indices and to analyze the risk of new-onset hypertension, taking into account sex and age. METHODS: This prospective cohort study utilized the Taiwan Biobank database to examine metabolically healthy participants aged between 20 and 65 at baseline. Four adiposity indices, namely BMI, WHR, WC, and WHtR, were calculated and used to predict new-onset hypertension over 4 years. Receiver operating characteristics (ROCs) and areas under the curve (AUCs) were used to evaluate the effectiveness of the parameters in predicting new-onset hypertension over 4 years. Sex-specific cutoff points were identified and used to assess the risk of new-onset hypertension. RESULTS: This study analyzed 13,375 participants over 4.28 years. The incidence of new-onset hypertension was 17.65%. The new-onset rate of hypertension was 34.39% in men and 65.61% in women. Adiposity indices effectively predict new-onset hypertension, with WHtR having the highest predictive value (i.e., AUC) for both sexes. The classification of participants into low and high categories for each adiposity index was based on sex-specific cutoff points, and the risk of new-onset hypertension was assessed according to sex and age. This study found that high adiposity indices predicted a significantly higher risk of new-onset hypertension in metabolically healthy adults. The risk was equal for both sexes. Young women had a higher risk of new-onset hypertension than middle-aged women when they were further categorized. All risk ratios of the indices in young women were over two-fold and significant. CONCLUSION: According to the sex-specific cutoff point, high adiposity indices had a higher predictive value for new-onset hypertension in metabolically healthy Taiwanese young women.

Adjuvant chemotherapy and survival outcomes in older women with HR+/HER2- breast cancer: a propensity score-matched retrospective cohort study using the SEER database.

OBJECTIVES: This study aimed to investigate the impact of adjuvant chemotherapy (ACT) on survival outcomes in older women with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC). DESIGN: A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database, which contains publicly available information from US cancer registries. SETTING AND PARTICIPANTS: The study included 45 762 older patients with BC aged over 65 years diagnosed between 2010 and 2015. METHODS: Patients were divided into two groups based on age: 65-79 years and ≥80 years. Propensity score matching (PSM) was employed to balance clinicopathological characteristics between patients who received ACT and those who did not. Data analysis used the χ2 test and Kaplan-Meier method, with a subgroup analysis conducted to identify potential beneficiaries of ACT. OUTCOME MEASURES: Overall survival (OS) and cancer-specific survival (CSS). RESULTS: Due to clinicopathological characteristic imbalances between patients with BC aged 65-79 years and those aged ≥80 years, PSM was used to categorise the population into two groups for analysis: the 65-79 years age group (n=38 128) and the ≥80 years age group (n=7634). Among patients aged 65-79 years, Kaplan-Meier analysis post-PSM indicated that ACT was effective in improving OS (p<0.05, HR=0.80, 95% CI 0.73 to 0.88), particularly in those with advanced disease stages, but did not show a significant benefit in CSS (p=0.09, HR=1.13, 95% CI 0.98 to 1.31). Conversely, for patients aged ≥80 years, ACT did not demonstrate any improvement in OS (p=0.79, HR=1.04, 95% CI 0.79 to 1.36) or CSS (p=0.09, HR=1.46, 95% CI 0.69 to 2.26) after matching. Subgroup analysis also revealed no positive impact on OS and CSS. CONCLUSIONS: Patients with HR+/HER2- BC ≥80 years of age may be considered exempt from ACT because no benefits were found in terms of OS and CSS.

Sensing of dietary amino acids and regulation of calcium dynamics in adipose tissues through Adipokinetic hormone in Drosophila.

Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various obesity-related diseases. Drosophila melanogaster has emerged as an excellent model for investigating metabolism and its associated disorders. In this study, we used live-cell imaging to demonstrate that the fly functional homolog of mammalian glucagon, Adipokinetic hormone (AKH), secreted from AKH hormone-producing cells (APCs) in the corpora cardiaca, stimulates intracellular Ca 2+ waves in the larval fat body/adipose tissue to promote lipid metabolism. Further, we show that specific dietary amino acids activate the APCs, leading to increased intracellular Ca 2+ and subsequent AKH secretion. Finally, a comparison of Ca 2+ dynamics in larval and adult fat bodies revealed different mechanisms of regulation, highlighting the interplay of pulses of AKH secretion, extracellular diffusion of the hormone, and intercellular communication through gap junctions. Our study underscores the suitability of Drosophila as a powerful model for exploring real-time nutrient sensing and inter-organ communication dynamics.

SADSNet: A robust 3D synchronous segmentation network for liver and liver tumors based on spatial attention mechanism and deep supervision.

Highlights: • Introduce a data augmentation strategy to expand the required different morphological data during the training and learning phase, and improve the algorithm's feature learning ability for complex and diverse tumor morphology CT images.• Design attention mechanisms for encoding and decoding paths to extract fine pixel level features, improve feature extraction capabilities, and achieve efficient spatial channel feature fusion.• The deep supervision layer is used to correct and decode the final image data to provide high accuracy of results.• The effectiveness of this method has been affirmed through validation on the LITS, 3DIRCADb, and SLIVER datasets. BACKGROUND: Accurately extracting liver and liver tumors from medical images is an important step in lesion localization and diagnosis, surgical planning, and postoperative monitoring. However, the limited number of radiation therapists and a great number of images make this work time-consuming. OBJECTIVE: This study designs a spatial attention deep supervised network (SADSNet) for simultaneous automatic segmentation of liver and tumors. METHOD: Firstly, self-designed spatial attention modules are introduced at each layer of the encoder and decoder to extract image features at different scales and resolutions, helping the model better capture liver tumors and fine structures. The designed spatial attention module is implemented through two gate signals related to liver and tumors, as well as changing the size of convolutional kernels; Secondly, deep supervision is added behind the three layers of the decoder to assist the backbone network in feature learning and improve gradient propagation, enhancing robustness. RESULTS: The method was testing on LITS, 3DIRCADb, and SLIVER datasets. For the liver, it obtained dice similarity coefficients of 97.03%, 96.11%, and 97.40%, surface dice of 81.98%, 82.53%, and 86.29%, 95% hausdorff distances of 8.96 mm, 8.26 mm, and 3.79 mm, and average surface distances of 1.54 mm, 1.19 mm, and 0.81 mm. Additionally, it also achieved precise tumor segmentation, which with dice scores of 87.81% and 87.50%, surface dice of 89.63% and 84.26%, 95% hausdorff distance of 12.96 mm and 16.55 mm, and average surface distances of 1.11 mm and 3.04 mm on LITS and 3DIRCADb, respectively. CONCLUSION: The experimental results show that the proposed method is effective and superior to some other methods. Therefore, this method can provide technical support for liver and liver tumor segmentation in clinical practice.

Lymph node volume predicts survival in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Pneumorrhachis With FDG Uptake Cervical Lesions on PET/CT of a Patient With Suspected Recurrent Hypopharyngeal Cancer.

ABSTRACT: A 57-year-old man presented with odynophagia for 1 week was referred for FDG PET/CT scan to rule out recurrent hypopharyngeal cancer. The FDG PET/CT showed hypermetabolic lesions in hypopharyngeal area and adjacent cervical spine with pneumorrhachis, the presence of intraspinal air, on attenuation CT images, which might indicate a life-threatening infection. An emergency MRI confirmed the presence of cervical spondylodiscitis with an epidural abscess. The patient rapidly progressed to quadriplegia and difficulty voiding on the same day as the PET/CT scan, leading to emergent operation. The patient received antibiotics treatment and discharged 4 months later without evidence of cancer recurrence.