IVIM parameters mapping with artificial neural network based on mean deviation prior.

BACKGROUND: The diffusion and perfusion parameters derived from intravoxel incoherent motion (IVIM) imaging provide promising biomarkers for noninvasively quantifying and managing various diseases. Nevertheless, due to the distribution gap between simulated and real datasets, the out-of-distribution (OOD) problem occurred in supervised learning-based methods degrades their performance and hinders their real applications. PURPOSE: To address the OOD problem in supervised methods and to further improve the accuracy and stability of IVIM parameter estimation, this work proposes a novel learning framework called IterANN, based on mean deviation prior (MDP) between training and estimated IVIM parameters on the test set. METHODS: Specifically, MDP indicates that the mean of the estimated IVIM parameters always locates between the mean of IVIM parameters in the test and train sets. In IterANN, we adopt a very simple artificial neural network (ANN) architecture of two hidden layers with 12 neurons per hidden layer, an input layer containing the signals acquired at multiple b-values and an output layer composed of three IVIM parameters ( D $D$ , F $F$ and D S t a r $DStar$ ). Inspired by MDP, the distribution of IVIM parameters in the training set (simulated data) is iteratively updated so that their mean gradually approaches the predicted values of the real data. This aims to achieve a strong correlation between the simulated data and the real data. To validate the effectiveness of IterANN, we compare it with several methods on both simulation and real acquisition datasets, including 21 healthy and 3 tumor subjects, in terms of residual errors of IVIM parameters or DW signals, the coefficients of variation (CV) of IVIM parameters, and the parameter contrast-to-noise ratio (PCNR) between normal and tumor tissues. RESULTS: On two simulation datasets, the proposed IterANN achieves the lowest residual error in IVIM parameters, especially in the case of low signal-to-noise ratio (SNR = 10), the residual error of D $D$ , F $F$ and D S t a r $DStar$ is decreased by 15.82 % / 14.92 % , 81.19 % / 74.04 % , 50.77 % / 1.549 % $15.82\%/14.92\%, 81.19\%/74.04\%, 50.77\%/1.549\%$ (Gaussian distribution /realistic distribution) respectively comparing to the suboptimal method. On real dataset, the IterANN achieves the highest PCNR when comparing the normal and tumor regions. Additionally, the proposed IterANN demonstrated better stability, with its CV being significantly lower than that of other methods in the vast majority of cases ( p < 0.01 $p<0.01$ , paired-sample Student's t-test). CONCLUSIONS: The superior performance of IterANN demonstrates that updating the distribution of the train set based on MDP can effectively solve the OOD problem, which allows us not only to improve the accuracy and stability of the estimated IVIM parameters, but also to increase the potential of IVIM in disease diagnosis.

How do filter types of renal replacement therapy affect survival in critically ill patients? Concerns about adsorption of nafamostat mesylate on AN69 membranes.

We are writing to you in response to the article published in BMC Nephrology titled "Dose of nafamostat mesylate during continuous kidney replacement therapy in critically ill patients: a two-centre observational study". The study provided valuable information on the use of nafamostat mesylate (NM) during continuous renal replacement therapy (CRRT) in critically ill patients. We noticed in this study that a higher dose of NM resulted in a decrease in ICU and hospital mortality. However, the underlying mechanism behind this phenomenon remains unclear. We believe exploring this further is warranted.

Pathophysiological dynamics in the contact, coagulation, and complement systems during sepsis: Potential targets for nafamostat mesilate.

Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection. It is the primary cause of death in the intensive care unit, posing a substantial challenge to human health and medical resource allocation. The pathogenesis and pathophysiology of sepsis are complex. During its onset, pro-inflammatory and anti-inflammatory mechanisms engage in intricate interactions, possibly leading to hyperinflammation, immunosuppression, and long-term immune disease. Of all critical outcomes, hyperinflammation is the main cause of early death among patients with sepsis. Therefore, early suppression of hyperinflammation may improve the prognosis of these patients. Nafamostat mesilate is a serine protease inhibitor, which can inhibit the activation of the complement system, coagulation system, and contact system. In this review, we discuss the pathophysiological changes occurring in these systems during sepsis, and describe the possible targets of the serine protease inhibitor nafamostat mesilate in the treatment of this condition.

Longitudinal changes of serum metabolomic profile after laparoscopic sleeve gastrectomy in obesity.

BACKGROUND: Bariatric surgery induces significant weight loss, increases insulin sensitivity and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement. METHODS: Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using non-targeted metabolic liquid chromatography-mass spectrometry (LC-MS) method. RESULTS: During the 1, 3, and 6 months postoperative follow-up, the BMI, HOMA-IR, liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement and liver fat content reduction. CONCLUSIONS: This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.

Novel cortisol trajectory sub-phenotypes in sepsis.

BACKGROUND: Sepsis is a heterogeneous syndrome. This study aimed to identify new sepsis sub-phenotypes using plasma cortisol trajectory. METHODS: This retrospective study included patients with sepsis admitted to the intensive care unit of Zhongshan Hospital Fudan University between March 2020 and July 2022. A group-based cortisol trajectory model was used to classify septic patients into different sub-phenotypes. The clinical characteristics, biomarkers, and outcomes were compared between sub-phenotypes. RESULTS: A total of 258 patients with sepsis were included, of whom 186 were male. Patients were divided into two trajectory groups: the lower-cortisol group (n = 217) exhibited consistently low and slowly declining cortisol levels, while the higher-cortisol group (n = 41) showed relatively higher levels in comparison. The 28-day mortality (65.9% vs.16.1%, P < 0.001) and 90-day mortality (65.9% vs. 19.8%, P < 0.001) of the higher-cortisol group were significantly higher than the lower-cortisol group. Multivariable Cox regression analysis showed that the trajectory sub-phenotype (HR = 5.292; 95% CI 2.218-12.626; P < 0.001), APACHE II (HR = 1.109; 95% CI 1.030-1.193; P = 0.006), SOFA (HR = 1.161; 95% CI 1.045-1.291; P = 0.006), and IL-1ß (HR = 1.001; 95% CI 1.000-1.002; P = 0.007) were independent risk factors for 28-day mortality. Besides, the trajectory sub-phenotype (HR = 4.571; 95% CI 1.980-10.551; P < 0.001), APACHE II (HR = 1.108; 95% CI 1.043-1.177; P = 0.001), SOFA (HR = 1.270; 95% CI 1.130-1.428; P < 0.001), and IL-1ß (HR = 1.001; 95% CI 1.000-1.001; P = 0.015) were also independent risk factors for 90-day mortality. CONCLUSION: This study identified two novel cortisol trajectory sub-phenotypes in patients with sepsis. The trajectories were associated with mortality, providing new insights into sepsis classification.

Downregulation of CIAPIN1 regulates the proliferation, migration and glycolysis of breast cancer cells via inhibition of STAT3 pathway.

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a protein that regulates apoptosis and programmed cell death. This research aims to evaluate its potential role in inhibiting breast cancer cell proliferation, migration, and glycolysis and uncover its underlying molecular mechanism. We collected breast cancer tissue samples from eight patients between January 2019 and June 2023 in our Hospital to analyse CIAPIN1 expression. We transfected human breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-453, and MDA-MB-468) with siRNA of CIAPIN1. Finally, we determined protein expression using RT-qPCR and Western blotting. CIAPIN1 expression was elevated in both breast cancer tissue and serum. Overexpression of CIAPIN1 detected in the breast cancer cell lines MCF7 and MDA-MB-468. In addition, CIAPIN1 overexpression increased cell proliferation and migration rate. CIAPIN1 downregulation suppressed cell proliferation while elevated cellular apoptosis, reactive oxygen species (ROS) production and oxidative stress in breast cancer cells. Moreover, CIAPIN1 inhibition remarkably suppressed pyruvate, lactate and adenosine triphosphate (ATP) production and reduced the pyruvate kinase M2 (PKM2) protein expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) in breast cancer cells. Downregulation of CIAPIN1 suppresses cell proliferation, migration and glycolysis capacity in breast cancer cells by inhibiting the STAT3/PKM2 pathway.

The Diagnostic and Therapeutic Value of Anti CCP Antibodies and Double Stranded DNA in Rhupus Syndrome.

BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of ˃ 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.

Lactoferrin/lactoferrin receptor: Neurodegenerative or neuroprotective in Parkinson's disease?

Lactoferrin (Lf) is a multifunctional protein in the transferrin family. It is involved in many physiological functions, including the regulation of iron absorption and immune response. It also has antibacterial, antiviral, anti-inflammatory, anticancer and antioxidant capabilities under pathophysiological conditions. The mammalian lactoferrin receptor (LfR) plays a key role in mediating multiple functions of Lf. Studies have shown that Lf/LfR is abnormally expressed in the brain of Parkinson's disease, and the excessive accumulation of iron in the brain caused by the overexpression of Lf and LfR is considered to be one of the initial causes of the degeneration of dopaminergic neurons in Parkinson's disease. On the other hand, a number of recent studies have reported that Lf/LfR has a significant neuroprotective effect on Parkinson's disease. In other words, it seems paradoxical that Lf/LfR has both neurodegenerative and neuroprotective effects in Parkinson's disease. This article focuses on recent advances in the possible mechanisms of the neurodegenerative and neuroprotective effects of Lf/LfR in Parkinson's disease and discusses why Lf/LfR has a seemingly contradictory role in the development of Parkinson's disease. Based on the evidence obtained so far, we believed that Lf/LfR has a neuroprotective effect on Parkinson's disease, while as to whether the overexpressed Lf/LfR is the cause of the development of Parkinson's disease, the current evidence is insufficient and further investigation needed.

Biodegradable magnesium and zinc composite microspheres with synergistic osteogenic effect for enhanced bone regeneration.

Biodegradable polymer microspheres in bone tissue engineering have become appealing as their non-invasive advantages in irregular damage bone repair. However, current microspheres used in BTE still lack sufficient osteogenic capacity to induce effective bone regeneration. In this study, we developed osteogenic composite microspheres concurrently loaded with magnesium oxide (MgO) and zinc oxide (ZnO), both of which are osteogenic active substances, using a facile and scalable emulsification method. The osteogenic composite microspheres exhibited a sequential yet complementary release profile characterized by a rapid release of Mg2+ and a gradual release of Zn2+ in a physiological environment, thereby maintaining the concentration of bioactive ions at a sustained high level. As a result, the combination of Mg2+ and Zn2+ in the composite microspheres led to a synergistic enhancement in biomimetic mineralization and the upregulation in the expression of osteogenic-related genes and proteins at the cellular level. Through a critical-sized calvarial rate defect model, the osteogenic composite microspheres were demonstrated to have strong osteogenic ability to promote new bone formation via ultrasonic imaging, histological and immunohistochemical evaluations. In sum, these osteogenic composite microspheres as microcarriers of Mg2+ and Zn2+ have great potential in the delivery of therapeutic ions for treating bone defects.

Constructing the Snail Shell-Like Framework in Thermal Interface Materials for Enhanced Through-Plane Thermal Conductivity.

Melioration of the through-plane thermal conductivity (TC) of thermal interface materials (TIMs) is a sore need for efficient heat dissipation to handle an overheating concern of high-power-density electronics. Herein, we constructed a snail shell-like thermal conductive framework to facilitate vertical heat conduction in TIMs. With inspiration from spirally growing calcium carbonate platelets of snail shells, a facile double-microrod-assisted curliness method was developed to spirally coil boron nitride nanosheet (BNNS)/aramid nanofiber (ANF) laminates where interconnected BNNSs lie along the horizontal plane. Thus, vertical alignment of BNNSs in the resultant TIM was achieved, exhibiting a through-plane TC enhancement of ∼100% compared to the counterpart with randomly distributed BNNSs at the same BNNS addition (50 wt %). The Foygel's nonlinear model revealed that this unique snail shell-like BNNS framework reduced interfacial thermal resistance by 4 orders of magnitude. Our TIM showed superior interfacial thermal dissipation efficiency, leading to a temperature reduction of 42.6 °C for the LED chip compared to the aforementioned counterpart. Our work paves a valuable way for fabricating high-performance TIMs to ensure reliable operation of electrical devices.

Intraspecific and interspecific resource partitioning between bumblebee workers and males related to nectar quantity and quality.

Bumblebees are important pollinators for many natural and agricultural systems in temperate regions. Interspecific and intraspecific variation in floral resource preferences have been proposed to influence bumblebee community structure. In particular, sexual dimorphism is a major source of intraspecific niche variation. Although interspecific resource partitioning is well studied, few studies have explored the intraspecific dynamics between workers and males. Here, we report a study on a total of 11 528 workers and 2220 males of 14 bumblebee species recorded over 5 years in the Hengduan Mountains of Southwest China. We first compared the potential for interspecific and intraspecific competition between workers and males using visitation records and resource partitioning indices (overlap index). We then evaluated the influence of nectar traits on flower preference, including nectar volume and the levels of hexose, sucrose and 10 essential amino acids (EAAs). We found that the niche overlap between intraspecific workers and males was higher than that between different species, and temporal overlap alone did not strongly determine diet overlap. Males of most species preferred flowers with high levels of EAAs and hexose, whereas workers of some species preferred flowers with high nectar volume and sucrose levels. This study suggests that there is floral resource partitioning among bumblebee species, and between workers and males, which may play a key role in alleviating interspecific and intraspecific competition. These findings also provide a useful guide for which kinds of plants might be most valuable for bumblebees, especially the understudied males, in this biodiversity hotspot.

Design and Construction of Carbon-Coated Bimetallic Selenide Heterostructures Loaded on Reduced Graphene Oxide Substrate for Superior Lithium-Ion Storage.

In this work, carbon-coated bimetallic tin-nickel selenide heterostructures loaded on reduced graphene oxide composites were prepared through a metal-organic framework-assisted strategy. The carbon coating mitigates the volume expansion and maintains the structural stability, while the introduction of reduced graphene oxide and heterojunction enhances electrical conductivity and reaction kinetics, thereby together contributing to the enhanced lithium-ion storage performance. As expected, the optimal material delivers excellent lithium-ion storage performance in terms of a high reversible capacity of 1033.4 mAh g-1 at 0.2 A g-1, outstanding rate capability, and long-term cyclability with the capacity of 726.2 mAh g-1 after 500 cycles at 1.0 A g-1 and 452.4 mAh g-1 after 1000 cycles at 2.0 A g-1. Furthermore, the electrochemical reaction mechanism of the composite is analyzed.

Extent of Lymphadenectomy for Surgical Management of Right-Sided Colon Cancer: The Randomized Phase III RELARC Trial.

PURPOSE: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. METHODS: This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). RESULTS: Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group). CONCLUSION: This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

Dynamics of discrete solitons in the fractional discrete nonlinear Schrödinger equation with the quasi-Riesz derivative.

We elaborate a fractional discrete nonlinear Schrödinger (FDNLS) equation based on an appropriately modified definition of the Riesz fractional derivative, which is characterized by its Lévy index (LI). This FDNLS equation represents a novel discrete system, in which the nearest-neighbor coupling is combined with long-range interactions, that decay as the inverse square of the separation between lattice sites. The system may be realized as an array of parallel quasi-one-dimensional Bose-Einstein condensates composed of atoms or small molecules carrying, respectively, a permanent magnetic or electric dipole moment. The dispersion relation (DR) for lattice waves and the corresponding propagation band in the system's linear spectrum are found in an exact form for all values of LI. The DR is consistent with the continuum limit, differing in the range of wave numbers. Formation of single-site and two-site discrete solitons is explored, starting from the anticontinuum limit and continuing the analysis in the numerical form up to the existence boundary of the discrete solitons. Stability of the solitons is identified in terms of eigenvalues for small perturbations, and verified in direct simulations. Mobility of the discrete solitons is considered too, by means of an estimate of the system's Peierls-Nabarro potential barrier, and with the help of direct simulations. Collisions between persistently moving discrete solitons are also studied.

Fabricating High Strength Bio-Based Dynamic Networks from Epoxidized Soybean Oil and Poly(Butylene Adipate-co-Terephthalate).

Amid the rapid development of modern society, the widespread use of plastic products has led to significant environmental issues, including the accumulation of non-degradable waste and extensive consumption of non-renewable resources. Developing healable, recyclable, bio-based materials from abundant renewable resources using diverse dynamic interactions attracts increasing global attention. However, achieving a good balance between the self-healing capacity and mechanical performance, such as strength and toughness, remains challenging. In our study, we address this challenge by developing a new type of dynamic network from epoxidized soybean oil (ESO) and poly(butylene adipate-co-terephthalate) (PBAT) with good strength and toughness. For the synthetic strategy, a thiol-epoxy click reaction was conducted to functionalize ESO with thiol and hydroxyl groups. Subsequently, a curing reaction with isocyanates generated dynamic thiourethane and urethane bonds with different bonding energies in the dynamic networks to reach a trade-off between dynamic features and mechanical properties; amongst these, the thiourethane bonds with a lower bonding energy provide good dynamic features, while the urethane bonds with a higher bonding energy ensure good mechanical properties. The incorporation of flexible PBAT segments to form the rational multi-phase structure with crystalline domains further enhanced the products. A typical sample, OTSO100-PBAT100, exhibited a tensile strength of 33.2 MPa and an elongation at break of 1238%, demonstrating good healing capacity and desirable mechanical performance. This study provides a promising solution to contemporary environmental and energy challenges by developing materials that combine mechanical and repair properties. It addresses the specific gap of achieving a trade-off between tensile strength and elongation at break in bio-based self-healing materials, promising a wide range of applications.

Apolipoprotein E deficiency leads to the polarization of splenic macrophages towards M1 phenotype by increasing iron content.

Apolipoprotein E (ApoE) plays a crucial role in iron homeostasis in the body, while macrophages are the principal cells responsible for handling iron in mammals. However, it is unknown whether ApoE can affect the functional subtypes and the iron handling capacity of splenic macrophages (SM). Here, we investigated the effects of ApoE deficiency (ApoE-/-) on the polarization and iron content of SM and its potential mechanisms. ApoE-/- was found to induce a significant increase in the expressions of M1 marker genes CD86, IL-1ß, IL-6, IL-12, TNF-α and iNOS and a reduction in M2 marker genes CD206, Arg-1, IL-10 and Ym-1 in SM of mice aged 28 weeks, Meanwhile, ApoE-/- caused a significant increase in iron content and expression of ferritin, transferrin receptor 1 (TfR1), iron regulatory protein 1 (IRP1) and heme oxygenase-1 (HO-1) and a reduction in ferroportin1 (Fpn1) in spleen and/or SM of mice aged 28 weeks. It was concluded that ApoE-/- can increase iron content through increased iron uptake mediated by TfR/ IRPs and decreased iron release mediated by Fpn1, leading to polarization of the SM to M1 phenotype.

Application of 11/13Fr suctioning ureteral access sheath and 8.55Fr single-use digital flexible ureteroscope in one-stage flexible ureteroscopic lithotripsy: an initial experience of 900 cases.

OBJECTIVES: To report our initial experience of one-stage flexible ureteroscopic lithotripsy(FURL) with 11/13Fr suctioning ureteral access sheath(UAS) and 8.55Fr single-use digital flexible ureteroscope(SDFU) in upper ureteral or renal calculi. MATERIALS AND METHODS: We retrospectively collected the clinical data of 900 adult patients with upper ureteral or renal calculi treated by FURL with 11/13Fr suctioning UAS and 8.55Fr SDFU from January 2022 to April 2024. Demographics, peri- and postoperative outcomes were assessed. RESULTS: In all, 40 of 940 cases(4.26%) failed to introduce UAS and required second-stage FURL because of ureterostenosis and were excluded. Mean stones size of the remaining 900 eligible cases was 1.68 ± 0.58 cm in greatest diameter. There were 228 cases of upper ureteral stone, 456 cases of renal stone and 216 cases of concomitant ureteral and renal calculi. The mean operation time was 52.20 ± 20.21 min and the postoperative hospital stay was 2.87 ± 1.37 days. The stone-free rate of 1 month postoperatively was 89.56% and only 2.44% of patients with residue underwent additional reoperation. The rate of postoperative fever, postoperative pain needing analgesic and slight ureteral mucosal injury were 5.11%, 8.22% and 7.78%, respectively. None of patient suffered from severe complications, such as sepsis or ureteral perforation. CONCLUSION: It's practical and suitable for the vast majority of adult patients to undergo FURL in single session with 11/13Fr suctioning UAS without preoperative stenting. FURL with 11/13Fr suctioning UAS and 8.55Fr SDFU is feasible, reliable, safe, and efficient in the management of renal stone and upper ureteral stone.

An arteriovenous fistula model: Carotid artery-posterior facial vein fistula in rats.

OBJECTIVE: To describe an alternative arteriovenous fistula (AVF) model involving anastomosis of the common carotid artery (CCA) with the posterior facial vein (PFV). METHODS: Twenty-two male Sprague-Dawley rats (age 6-8 weeks) were used to establish the AVF model involving end-to-side anastomosis of PFV and CCA. The peak velocity of the CCA and the diameter of the outflow vein were recorded at 7, 14, and 42 days after the operation using Doppler ultrasound. Pathological examination of the intimal lesions was performed at 14 and 42 days after operation. RESULTS: One rat died within 24 h after surgery related to anesthesia. The patency rates at days 7, 14, and 42 were 85.7%, 81%, and 81%, respectively. The diameter of the carotid artery in rats is approximately 0.8 mm. The diameter of the outflow vein was increased by 1.7-fold and 2.2-fold at 7 days (1.1 ± 0.118 mm) and 14 days (1.4 ± 0.073 mm). At 42 days (1.96 ± 0.101 mm) after operation, the diameter was 3-fold greater compared to the unoperated control rat. The peak systolic flow velocity of the carotid artery at 7 days (593 ± 17.36 mm/s) and 14 days (767 ± 13.64 mm/s) after surgery was significantly greater compared to the control rat (314 ± 15.13 mm/s). The rate of increase was fastest at 7 days and leveled off from 14 to 42 days (875 ± 26 mm/s) after surgery. At 14 days, the intima area showed a nearly 50-fold increase (230 ± 9.93 µm2 × 103) compared to control (area 5 ± 0.37 µm2 × 103). Comparing 6 weeks with 2 weeks (280 ± 10.54 µm2 × 103) after surgery, the intima area increased 1.2 times. CONCLUSION: The CCA-PFV fistula in rats is a viable alternative AVF model.

GENEVIC: GENetic data exploration and visualization via intelli- gent interactive console.

SUMMARY: The vast generation of genetic data poses a significant challenge in efficiently uncovering valuable knowledge. Introducing GENEVIC, an AI-driven chat framework that tackles this challenge by bridging the gap between genetic data generation and biomedical knowledge discovery. Leveraging generative AI, notably ChatGPT, it serves as a biologist's 'copilot'. It automates the analysis, retrieval, and visualization of customized domain-specific genetic information, and integrates functionalities to generate protein interaction networks, enrich gene sets, and search scientific literature from PubMed, Google Scholar, and arXiv, making it a comprehensive tool for biomedical research. In its pilot phase, GENEVIC is assessed using a curated database that ranks genetic variants associated with Alzheimer's disease, schizophrenia, and cognition, based on their effect weights from the Polygenic Score (PGS) Catalog, thus enabling researchers to prioritize genetic variants in complex diseases. GENEVIC's operation is user-friendly, accessible without any specialized training, secured by Azure OpenAI's HIPAA-compliant infrastructure, and evaluated for its efficacy through real-time query testing. As a prototype, GENEVIC is set to advance genetic research, enabling informed biomedical decisions. AVAILABILITY AND IMPLEMENTATION: GENEVIC is publicly accessible at https://genevic- anath2024.streamlit.app. The underlying code is open-source and available via GitHub at https://github.com/bsml320/GENEVIC.git (also at https://github.com/anath2110/GENEVIC.git). SUPPLEMENTARY INFORMATION: Available at Bioinformatics online and at https://github.com/bsml320/GENEVIC_Supplementary.git (also at https://github.com/anath2110/GENEVIC_Supplementary.git).