bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal congenital anomalies requiring surgery: diagnosis, counselling, and management
Authors: Mires Stuart , Raychoudhury Arun , Overton Timothy , Skerritt Clare , Eastwood Kelly‐Ann
Published: June 2023

Key content

Congenital anomalies affect more than 2% of fetuses in the UK, with 70% noncardiac in origin. Around 10% are gastrointestinal anomalies such as abdominal wall defects and intestinal atresias.

Most gastrointestinal anomalies require postnatal surgical management.

Obstetricians must understand the key features of diagnosis and management of common gastrointestinal anomalies.

Clinically relevant and evidence‐based information helps facilitate parental reproductive autonomy through timely and informed counselling, planning for delivery and optimising perinatal outcomes.

Management of pregnancies complicated by congenital gastrointestinal anomalies requires a multidisciplinary approach with specialist input.

Learning objectives

To be familiar with the antenatal diagnosis of gastrointestinal anomalies, associated conditions and potential obstetric complications

To understand the antenatal and postnatal management of gastrointestinal anomalies including the approach to surgery

To appreciate the role of multidisciplinary counselling in fetal medicine

Ethical issues

Antenatal counselling in the context of diagnostic and outcome uncertainties

Consideration of termination of pregnancy for fetal anomaly, including grounds for, and timing of, decision‐making
Artificial Intelligence Aided Design of Hull Form of Unmanned Underwater Vehicles for Minimization of Energy Consumption
Authors: Ao Yu , Xu Jian , Zhang Dapeng , Li Shaofan
Published: June 2023

Designing an excellent hull to reduce the sailing path energy consumption of UUVs is crucial for improving the energy endurance of UUVs. However, path energy consumption-based UUV hull design requires a tremendous amount of calculation due to the frequent changes in relative velocity and attack angle between a UUV and ocean current. In order to address this issue, this work developed a data-driven design methodology for energy consumption-based UUV hull design using artificial intelligence-aided design (AIAD). The design methodology in this work combined a deep learning (DL) algorithm that predicts UUVs’ resistance with different hull shapes under different velocities and attack angles with the particle swarm optimization (PSO) algorithm for UUV hull design. We tested the proposed methodology in a path energy consumption-based experiment, where the optimized UUV hull showed an 8.8% reduction in path energy consumption compared with the initial UUV hull, and design costs were greatly reduced compared with the traditional computational fluid dynamics (CFD)-based methodology. Our work demonstrates that AIAD has the potential to solve UUV design problems previously thought to be too complex by offering a data-driven engineering shape (body surface) design method.
Net-HDMR Metamodeling Method for High-Dimensional Problems
Authors: Liu Jie , Zhao Yue , Lei Fei , Ding Fei
Published: June 2023

Metamodel technology provides an efficient method to approximate complex engineering design problems. However, the approximation for high-dimensional problems usually requires a large number of samples for most traditional metamodeling methods, which leads to the difficulty of “curse of dimensionality.” To address the aforementioned issue, this paper presents the Net-high dimension model representation (HDMR) method based on the Cut-HDMR framework. Compared with traditional HDMR modeling, the Net-HDMR method incorporates two novel modeling approaches that improve the modeling efficiency of high-dimensional problems. The first approach enhances the modeling accuracy of HDMR by using the net function interpolation method to decompose the component functions into a series of one-dimensional net functions. The second approach adopts the CV-Voronoi sequence sampling method to effectively represent one-dimensional net functions with limited samples. Overall, the proposed method transforms complex high-dimensional problems into fitting finite one-dimensional splines, thereby increasing the modeling efficiency while ensuring approximate accuracy. Six numerical benchmark examples with different dimensions are examined to demonstrate the accuracy and efficiency of the proposed Net-HDMR. An engineering problem of thermal stress and deformation analysis for a jet engine turbine blade was introduced to verify the engineering feasibility of the proposed Net-HDMR.
Influences of Laser Incidence Angle and Wall Thickness on Additive Components
Authors: Wildgoose Alexander J. , Thole Karen A.
Published: June 2023

Additive manufacturing (AM), particularly laser powder bed fusion, is growing the ability to rapidly develop advanced cooling schemes for turbomachinery applications. However, to fully utilize the design and development opportunities offered through AM, impacts of the build considerations and processing parameters are needed. Prior literature has shown that specific build considerations such as laser incidence angle and wall thickness influence the surface roughness of additively made components. The objective of this technical brief is to highlight the effects of both laser incidence angle and wall thickness on the surface roughness and cooling performance in micro-sized cooling passages. Results indicate that for any given laser incidence angle, surface roughness begins to increase when the wall thickness is less than 1 mm for the cooling channels evaluated. As the laser incidence angle becomes further away from 90 deg, the surface roughness increases in a parabolic form. Laser incidence angle and wall thickness significantly impact friction factor, while there is less of an influence on the Nusselt number for additively manufactured microchannels.
A Deep Learning-Based Surrogate Model for Complex Temperature Field Calculation With Various Thermal Parameters
Authors: Zhu Feiding , Chen Jincheng , Ren Dengfeng , Han Yuge
Published: June 2023

Surrogate models of temperature field calculation based on deep learning have gained popularity in recent years because it does not need to establish complex mathematical models. However, the existing models cannot generate the temperature field for different boundary conditions or thermal parameters. In addition, it is also challenging to generate the details of the complex temperature field. In this paper, we propose the Parameters-to-Temperature Generative Adversarial Network (PTGAN) to generate temperature field images with high-quality details for different thermal parameters. The PTGAN model mainly includes the temperature field generation module and the thermal parameter encoding module. Additionally, we use a joint loss function to improve the quality of the generated temperature field image. The temperature field of the armored vehicle is calculated by the computational fluid dynamics method to obtain data set to verify the proposed PTGAN. The results show that the temperature images generated by the PTGAN has high accuracy, and the average relative error is only 0.205%. The attempt to integrate thermal parameters into the temperature field image generation is successful. The temperature field database can be generated quickly and accurately, which is of great significance for the further integration of deep learning and heat transfer.
Mixed Lubrication Analysis of Scrolls Lubricated With CO2/Oil Mixture Based on a Homogeneous Model
Authors: Wei Chunjie , Song Hui , Hu Zhaowen , Wang Wei
Published: June 2023

The tribological performance of scrolls lubricated with CO2/oil mixture is investigated using a combination of the mixed lubrication model and the homogeneous model. The physical characteristics of the CO2/oil mixture were established prior to using the lubrication model. Then the evolution of the lubrication condition during the meshing process of scrolls was investigated, and the impact of radial clearance and refrigerant on the tribological behavior was assessed. The lubrication condition of the tribo-pair deteriorates as the meshing point moves toward the center of the scrolls. The effects of radial clearance and refrigerant mass fraction on friction and lubrication are strongly influenced by the meshing position. In addition, the presence of refrigerant leads to less hydrodynamic pressure and more asperity contact.
Recovery of spatially varying acoustical properties via automated partial differential equation identification
Authors: Liu Ruixian , Gerstoft Peter , Bianco Michael J , Rao Bhaskar D.
Published: June 2023

Observable dynamics, such as waves propagating on a surface, are generally governed by partial differential equations (PDEs), which are determined by the physical properties of the propagation media. The spatial variations of these properties lead to spatially dependent PDEs. It is useful in many fields to recover the variations from the observations of dynamical behaviors on the material. A method is proposed to form a map of the physical properties' spatial variations for a material via data-driven spatially dependent PDE identification and applied to recover acoustical properties (viscosity, attenuation, and phase speeds) for propagating waves. The proposed data-driven PDE identification scheme is based on ℓ1-norm minimization. It does not require any PDE term that is assumed active from the prior knowledge and is the first approach that is capable of identifying spatially dependent PDEs from measurements of phenomena. In addition, the method is efficient as a result of its non-iterative nature and can be robust against noise if used with an integration transformation technique. It is demonstrated in multiple experimental settings, including real laser measurements of a vibrating aluminum plate. Codes and data are available online at https://tinyurl.com/4wza8vxs.
REVIEWS OF ACOUSTICAL PATENTS
Authors: Fulop Sean A.
Published: June 2023

The purpose of these acoustical patent reviews is to provide enough information for a Journal reader to decide whether to seek more information from the patent itself. Any opinions expressed here are those of the reviewers as individuals and are not legal opinions. Patents are available via the internet at the USPTO website.
Bioengineered particles expand myelin-specific regulatory T cells and reverse autoreactivity in a mouse model of multiple sclerosis
Authors: Rhodes Kelly R. , Tzeng Stephany Y. , Iglesias Marcos , Lee Dongwoo , Storm Kaitlyn , Neshat Sarah Y. , VanDyke Derek , Lowmaster Shirley M. , Spangler Jamie B. , Raimondi Giorgio , Green Jordan J.
Published: June 2023

Multiple sclerosis (MS) is an autoimmune disease characterized by autoreactive immune cells damaging myelinated nerves, impairing brain function. Treatments aim for tolerance induction to reeducate the immune system to recognize myelin as “self” rather than “foreign.” As peripheral immune tolerance is primarily mediated by regulatory T cells (T
regs
), we developed a therapy to support T
reg
expansion and activity in vivo. To target, engage, and activate myelin-specific T
regs
, we designed a biodegradable microparticle (MP) loaded with rapamycin and functionalized with a biased interleukin-2 (IL-2) fusion protein and a major histocompatibility complex (MHC) class II loaded with a myelin peptide. These tolerogenic MPs (Tol-MPs) were validated in vitro and then evaluated in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Tol-MPs promoted sustained disease reversal in 100% of mice and full recovery in 38% of mice with symptomatic EAE. Tol-MPs are a promising platform for treatment of autoimmune diseases.
Plug-and-play fiber-optic sensors based on engineered cells for neurochemical monitoring at high specificity in freely moving animals
Authors: Zhou Bingqian , Fan Kuikui , Guo Jingjing , Feng Jiesi , Yang Changxi , Li Yulong , Shi Songhai , Kong Lingjie
Published: June 2023

In vivo detection of neurochemicals, including neurotransmitters and neuromodulators, is critical for both understanding brain mechanisms and diagnosing brain diseases. However, few sensors are competent in monitoring neurochemical dynamics in vivo at high specificity. Here, we propose the fiber-optic probes based on engineered cells (FOPECs) for plug-and-play, real-time detection of neurochemicals in freely moving animals. Taking advantages of life-evolved neurochemical receptors as key components, the chemical specificity of FOPECs is unprecedented. We demonstrate the applications of FOPECs in real-time monitoring of neurochemical dynamics under various physiology and pathology conditions. With no requirement of viral infection in advance and no dependence on animal species, FOPECs can be widely adopted in vertebrates, such as mice, rats, rabbits, and chickens. Moreover, FOPECs can be used to monitor drug metabolisms in vivo. We demonstrated the neurochemical monitoring in blood circulation systems in vivo. We expect that FOPECs will benefit not only neuroscience study but also drug discovery.
Performance of a prehospital HEART score in patients with possible myocardial infarction: a prospective evaluation
Authors: Cooper Jamie G , Ferguson James , Donaldson Lorna A , Black Kim M M , Livock Kate J , Horrill Judith L , Davidson Elaine M , Scott Neil W , Lee Amanda J , Fujisawa Takeshi , Lee Kuan Ken , Anand Atul , Shah Anoop S V , Mills Nicholas L
Published: June 2023

Introduction

The History, Electrocardiogram (ECG), Age, Risk Factors and Troponin (HEART) score is commonly used to risk stratify patients with possible myocardial infarction as low risk or high risk in the Emergency Department (ED). Whether the HEART score can be used by paramedics to guide care were high-sensitivity cardiac troponin testing available in a prehospital setting is uncertain.

Methods

In a prespecified secondary analysis of a prospective cohort study where paramedics enrolled patients with suspected myocardial infarction, a paramedic Heart, ECG, Age, Risk Factors (HEAR) score was recorded contemporaneously, and a prehospital blood sample was obtained for subsequent cardiac troponin testing. HEART and modified HEART scores were derived using laboratory contemporary and high-sensitivity cardiac troponin I assays. HEART and modified HEART scores of ≤3 and ≥7 were applied to define low-risk and high-risk patients, and performance was evaluated for an outcome of major adverse cardiac events (MACEs) at 30 days.

Results

Between November 2014 and April 2018, 1054 patients were recruited, of whom 960 (mean 64 (SD 15) years, 42% women) were eligible for analysis and 255 (26%) experienced a MACE at 30 days. A HEART score of ≤3 identified 279 (29%) as low risk with a negative predictive value of 93.5% (95% CI 90.0% to 95.9%) for the contemporary assay and 91.4% (95% CI 87.5% to 94.2%) for the high-sensitivity assay. A modified HEART score of ≤3 using the limit of detection of the high-sensitivity assay identified 194 (20%) patients as low risk with a negative predictive value of 95.9% (95% CI 92.1% to 97.9%). A HEART score of ≥7 using either assay gave a lower positive predictive value than using the upper reference limit of either cardiac troponin assay alone.

Conclusions

A HEART score derived by paramedics in the prehospital setting, even when modified to harness the precision of a high-sensitivity assay, does not allow safe rule-out of myocardial infarction or enhanced rule-in compared with cardiac troponin testing alone.
Ethical preparedness and developments in genomic healthcare
Authors: Farsides Bobbie , Lucassen Anneke M
Published: June 2023

Considerations of the notion of preparedness have come to the fore in the recent pandemic, highlighting a need to be better prepared to deal with sudden, unexpected and unwanted events. However, the concept of preparedness is also important in relation to planned for and desired interventions resulting from healthcare innovations. We describe ethical preparedness as a necessary component for the successful delivery of novel healthcare innovations, and use recent advances in genomic healthcare as an example. We suggest that practitioners and organisations charged with delivering innovative and ambitious healthcare programmes can only succeed if they are able to exhibit the attribute of ethical preparedness.
Early rituximab treatment reduces long-term disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum
Authors: Park Su Yeon , Kwon Young Nam , Kim Sunyoung , Kim Seung-Hyun , Kim Jong Kuk , Kim Jun-Soon , Nam Tai-Seung , Min Young Gi , Park Kyung Seok , Park Jin-Sung , Seok Jin Myoung , Sung Jung-Joon , Sohn Eunhee , Shin Kyong Jin , Shin Jin-Hong , Shin Ha Young , Oh Seong-il , Oh Jeeyoung , Yoon Byeol-A , Lee Sanggon , Lee Jong-Mok , Lee Hye Lim , Choi Kyomin , Huh So-Young , Jang Myoung-jin , Min Ju-Hong , Kim Byoung Joon , Kim Sung-Min
Published: June 2023

Background

Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD.

Methods

This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis.

Results

In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment.

Conclusions

Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.
Does medical humanities matter? The challenge of COVID-19
Authors: Macnaughton Jane
Published: June 2023

Medical humanities has tended first and foremost to be associated with the ways in which the arts and humanities help us to understand health. However, this is not the only or necessarily the primary aim of our field. What the COVID-19 pandemic has revealed above all is what the field ofcriticalmedical humanities has insisted on: the deep entanglement of social, cultural, historical life with the biomedical. The pandemic has been a time for reinstating the power of expertise of a particular kind, focusing on epidemiology, scientific modelling of potential outcomes and vaccine development. All of this delivered by science at speed.

It has been challenging for medical humanities researchers to find purchase in these debates with insights from our more contemplative, ‘slow research’ approaches. However, as the height of the crisis passes, our field might now be coming into its own. The pandemic, as well as being productive of scientific expertise, also demonstrated clearly the meaning of culture: that it is not a static entity, but is produced and evolves through interaction and relationship. Taking a longer view, we can see the emergence of a certain ‘COVID-19 culture’ characterised by entanglements between expert knowledge, social media, the economy, educational progress, risk to health services and people in their socio-economic, political ethnic and religious/spiritual contexts. It is the role of medical humanities to pay attention to those interactions and to examine how they play out in the human experience and potential impact of the pandemic. However, to survive and grow in significance within the field of healthcare research, we need to engage not just to comment. There is a need for medical humanities scholars to assert our expertise in interdisciplinary research, fully engaged with experts by experience, and to work proactively with funders to demonstrate our value.
Impact of string interactions on the space–time evolution of hadronic vertices
Authors: Chakraborty Smita , Lönnblad Leif
Published: June 2023

We investigate the space–time picture of string evolution and hadron production in a fully string-based model for high energy collisions involving heavy-ions. We find that although the density of strings is quite large at the time of hadronization in a central heavy-ion collision, the initial overlap between them right after the collisions is not necessarily large. We also find that when including string-string interactions using the so-called shoving model, the density of strings is decreased which should dampen the rapid increase in string tension in the rope hadronization with multiplicity that we found in a previous paper.
Co-movement between RMB and Bitcoin with Effects of DCEP Using Wavelet Coherence Analysis
Authors: Wu Liang , Zhang Weifang
Published: June 2023

Utilizing wavelet coherence analysis, we investigate the correlation of fluctuations and phase differences between Bitcoin and RMB to identify capital flows between the two currencies. The effects of Digital Currency Electronic Payment (DCEP) on their co-movement are further analyzed. Our findings reveal that the RMB exchange rate leads the price of Bitcoin in all significant co-movement areas. Furthermore, it appears that from February 2017 to September 2018, the Sino-US trade frictions and US dollar interest rate hikes may have resulted in a long-term negative co-movement, which seems to have been driven by RMB and possibly indicated capital flows from RMB to Bitcoin. The short-term positive co-movement between November 2019 and July 2020 could be attributed to the COVID-19 pandemic. Finally, we also demonstrate that the DCEP trial event has the potential to strengthen the positive co-movement between these currencies.
A simple Bessel module with tunable focal depth and constant resolution for commercial two-photon microscope
Authors: Mo Ting , Liu Yiran , Bie Fatao , Dai Zimin , Chang Jin , Gong Hui , Zhou Wei
Published: June 2023

The volumetric imaging of two-photon microscopy expands the focal depth and improves the throughput, which has unparalleled superiority for three-dimension samples, especially in neuroscience. However, emerging in volumetric imaging is still largely customized, which limits the integration with commercial two-photon systems. Here, we analyzed the key parameters that modulate the focal depth and lateral resolution of polarized annular imaging and proposed a volumetric imaging module that can be directly integrated into commercial two-photon systems using conventional optical elements. This design incorporates the beam diameter adjustment settings of commercial two-photon systems, allowing flexibility to adjust the depth of focus while maintaining the same lateral resolution. Further, the depth range and lateral resolution of the design were verified, and the imaging throughput was demonstrated by an increase in the number of imaging neurons in the awake mouse cerebral cortex.
Safer Motion Planning of Steerable Needles via a Shaft-to-Tissue Force Model
Authors: Bentley Michael , Rucker Caleb , Reddy Chakravarthy , Salzman Oren , Kuntz Alan
Published: June 2023

Steerable needles are capable of accurately targeting difficult-to-reach clinical sites in the body. By bending around sensitive anatomical structures, steerable needles have the potential to reduce the invasiveness of many medical procedures. However, inserting these needles with curved trajectories increases the risk of tissue damage due to perpendicular forces exerted on the surrounding tissue by the needle’s shaft, potentially resulting in lateral shearing through tissue. Such forces can cause significant tissue damage, negatively affecting patient outcomes. In this work, we derive a tissue and needle force model based on a Cosserat string formulation, which describes the normal forces and frictional forces along the shaft as a function of the planned needle path, friction model and parameters, and tip piercing force. We propose this new force model and associated cost function as a safer and more clinically relevant metric than those currently used in motion planning for steerable needles. We fit and validate our model through physical needle robot experiments in a gel phantom. We use this force model to define a bottleneck cost function for motion planning and evaluate it against the commonly used path-length cost function in hundreds of randomly generated three-dimensional (3D) environments. Plans generated with our force-based cost show a 62% reduction in the peak modeled tissue force with only a 0.07% increase in length on average compared to using the path-length cost in planning. Additionally, we demonstrate planning with our force-based cost function in a lung tumor biopsy scenario from a segmented computed tomography (CT) scan. By directly minimizing the modeled needle-to-tissue force, our method may reduce patient risk and improve medical outcomes from steerable needle interventions.
Chloride Induced Secondary Passive Film Failure for Laser Additive Manufacturing Nickel-Based Superalloys during Electrochemical Machining
Authors: Guo Pengfei , Lin Xin , Macdonald Digby D. , Odnevall Inger , Zhang Shaoli , Zhang Yufeng , Lin Changjian , Wu Qiang , Yang Yuan , Huang Weidong
Published: June 2023

We investigated the influence of chloride on the secondary passive film (SPF) on laser directed energy deposition Alloy 718 during electrochemical machining. The results show that SPF formed in chloride-containing electrolyte is more defective than that formed in chloride-free solution, due to the stepped-up cation ejection by chloride. Chloride accelerates the SPF failure via enhanced cation vacancy condensation, SPF dissolution and possibly via surface vacancy pairs’ coalescence, restraining the formation of CrO3 and inducing a better surface quality than does the chloride-free electrolyte. Based on the Point Defect Model, a mechanism describing the influence of chloride on SPF was developed.
Dual-Band Metamaterial-Based EBG Antenna for Wearable Wireless Devices
Authors: Dam Trong Hieu , Le Minh Thuy , Nguyen Quoc Cuong , Nguyen Thanh Tung
Published: June 2023

In this paper, a wearable dual-band T-shaped antenna using a coplanar waveguide (CPW) fed operating at 2.4 GHz and 5.2 GHz bands is proposed for onbody wireless communications applications. Without the metamaterial-based electromagnetic bandgap (EBG) layer, the original antenna covers two bands from 1.96 GHz to 2.77 GHz and from 5.07 GHz to 5.35 GHz. The antenna efficiency decreases when it is placed on the human arm due to the interference from the human body to the antenna, as shown by a high specific absorption rate (SAR) value. These SAR values are reduced to 77.1% at 2.4 GHz and 91.7% at 5.2 GHz by the proposed EBG. The antenna gain is therefore improved to 1.4 dBi at 2.4 GHz and 6.25 dBi at 5.2 GHz. The antenna prototype is evaluated using a Wi-Fi wearable device, resulting in an improved signal-to-noise ratio (SNR) of 6-12 dB.
Effects of Astragalus membranaceus Polysaccharides on Growth Performance, Physiological and Biochemical Parameters, and Expression of Genes Related to Lipid Metabolism of Spotted Sea Bass, Lateolabrax maculatus
Authors: Huang Zhangfan , Ye Youling , Xu Anle , Li Zhongbao
Published: June 2023

This experiment investigated the effects of Astragalus membranaceus polysaccharides (AMP) on growth, physiological and biochemical parameters, and the expression of lipid metabolism-related genes in spotted sea bass, Lateolabrax maculatus. A total of 450 spotted sea bass (

10.44
±
0.09

 g) were divided into six groups and were given diets with different levels of AMP (0, 0.2, 0.4, 0.6, 0.8, and 1.0 g/kg) for 28 days, respectively. Results indicated that dietary intake of AMP significantly improved fish weight gain, specific growth rate, feed conversion, and trypsin activity. Meanwhile, fish fed with AMP manifested significantly higher serum total antioxidant capacity and activity of hepatic superoxide dismutase, catalase, and lysozyme. Lower triglyceride and total cholesterol were noted in fish fed with AMP (

P
<
0.05

). Moreover, hepatic ACC1 and ACC2 were downregulated by dietary intake of AMP, and PPAR-α, CPT1, and HSL were upregulated accordingly (

P
<
0.05

). Parameters with significant difference were analyzed by quadratic regression analysis, and results showed that 0.6881 g/kg of AMP is the optimal dosage for spotted sea bass in size (

10.44
±
0.09

 g). In conclusion, dietary intake of AMP can improve the growth, physiological status, and lipid metabolism of spotted sea bass, thereby indicating its promise as a potential dietary supplement.
A SiO2 Hybrid Enzyme-Based Biosensor with Enhanced Electrochemical Stability for Accuracy Detection of Glucose
Authors: Mei Li , Yang Yiting , Li Jiagen , Shang Shuyong , Fu Xiaohong
Published: June 2023

A novel enzyme-based biosensor for glucose detection is successfully developed using layer-by-layer assembly technology. The introduction of commercially available SiO2 was found to be a facile way to improve overall electrochemical stability. After 30 CV cycles, the proposed biosensor could retain 95% of its original current. The biosensor presents good detection stability and reproducibility with the detection concentration range of 1.96 × 10−9 to 7.24 × 10−7 M. This study demonstrated that the hybridization of cheap inorganic nanoparticles was a useful method in preparing high-performance biosensors with a much lower cost.
Substantia Nigra Echogenicity Signal Correlated with Clinical Features in Patients with Parkinson’s Disease in Xinjiang
Authors: Wei Rurui , Zhang Yan , Li Peishan , Xu Zeheng , Zhang La , He Yan , Wu Qinfen , Shi Youcai , Yuan Yang , Aisha Abudula
Published: June 2023

Background. Transcranial sonography (TCS) is a noninvasive test that can reveal structural changes in the substantia nigra (SN) in Parkinson’s disease (PD). The purpose of this study was to investigate the relationship between SN signatures and clinical features in PD patients in a multiethnic region of China. Methods. A total of 147 patients with PD were included in the study, and all of whom had underwent a TCS examination. Clinical information was collected from PD patients, and motor and nonmotor symptoms were assessed using assessment scales. Results. There were differences in the substantia nigra hyperechogenicity (SNH) area between age of onset, visual hallucinations (VH), and UPDRS3.0 II scores (

P

 < 0.05), patients with late onset PD had a greater SNH area than early onset (0.326 ± 0.352 vs. 0.171 ± 0.194), and PD patients presenting with VH had a greater SNH area than those without hallucinations (0.508 ± 0.670 vs. 0.278 ± 0.659), and further multifactorial analysis showed that a high SNH area was an independent risk factor for development of VH. The area under the ROC curve for predicting VH from the SNH area in PD patients was 0.609 (95% CI: 0.444–0.774). There was a positive correlation between the SNH area and UPDRS3.0-II scores, but further multifactorial analysis showed that SNH was not an independent predictor of the UPDRS3.0-II score. Conclusion. A high SNH area is an independent risk factor for development of VH, there is a positive correlation between the SNH area and UPDRS3.0 II score, and TCS has guiding significance in predicting clinical VH symptoms and activities of daily living in PD patients.
The Effect of High-Speed Power Training on Physical Frailty in Older Adults: Effect of a Visual-Guided Exercise Program in South Korean Rural Areas
Authors: Yoon Dong Hyun , Kim Jin-Soo , Hwang Su Seung , Lee Dong Won , Song Wook
Published: June 2023

Objective. Exercise has been shown to be an effective intervention; the difficulty still lies in providing exercise programs to the older adults in rural areas. Therefore, this study aimed to examine the effects of a 12-week exercise program provided with visual guidelines (prerecorded video) on frailty among older adults in rural areas. Methods. Fifty participants (71.7 ± 4.9 years) from 5 different rural areas were recruited and divided into two groups: the exercise group (EX, n = 24 (male: 8, female: 18)) and the control group (CON, n = 26 (male: 7, female: 17)). With the commencement of the exercise intervention, a prerecorded high-speed power training program for frail older adults was distributed to the EX group. A new prerecorded exercise program was delivered to the EX group every 4 weeks. Frailty status was diagnosed with Fried’s criteria before and after the intervention. Muscle strength was measured in the upper and lower limb strength (hand-grip strength and leg extension and flexion), and physical function was measured using a short physical performance battery and gait speed. Fasting blood was collected before and after the intervention and analyzed for blood lipid profile. Results. After 12 weeks of the intervention period, a significant difference in frailty status (

P
<
0.01

) and score (

P
<
0.01

) favoring the EX group was observed. Physical functions (gait speed (

P
=
0.01

) and time for sit to stand (

P
<
0.01

)) were significantly improved in the EX group with a significant increase in knee extensor strength (

P
<
0.01

). A significant difference in serum high-density lipoprotein levels favoring the EX group (

P
=
0.03

) was also observed. Conclusions. This study confirmed the positive effect of a visual-guided exercise program on older adults’ residents in rural areas and provided alternative methods to effectively provide exercise program for the older adults with limited resources.
Supplementary Table from Terminally Exhausted CD8+ T Cells Resistant to PD-1 Blockade Promote Generation and Maintenance of Aggressive Cancer Stem Cells
Authors: Chakravarti Mohona , Dhar Sukanya , Bera Saurav , Sinha Abhipsa , Roy Kamalika , Sarkar Anirban , Dasgupta Shayani , Bhuniya Avishek , Saha Akata , Das Juhina , Banerjee Saptak , Vernekar Manisha , Pal Chiranjib , Alam Neyaz , Datta Dipak , Baral Rathindranath , Bose Anamika
Published: June 2023

Contains supplementary table ST1, ST2 and ST3.
Supplementary Table 5 from Comprehensive DNA Methylation Analysis Indicates That Pancreatic Intraepithelial Neoplasia Lesions Are Acinar-Derived and Epigenetically Primed for Carcinogenesis
Authors: Lo Emily K.W. , Mears Brian M. , Maurer H. Carlo , Idrizi Adrian , Hansen Kasper D. , Thompson Elizabeth D. , Hruban Ralph H. , Olive Kenneth P. , Feinberg Andrew P.
Published: June 2023

Pairwise comparisons of promoter jsDMRs
Supplementary Table 2 from Comprehensive DNA Methylation Analysis Indicates That Pancreatic Intraepithelial Neoplasia Lesions Are Acinar-Derived and Epigenetically Primed for Carcinogenesis
Authors: Lo Emily K.W. , Mears Brian M. , Maurer H. Carlo , Idrizi Adrian , Hansen Kasper D. , Thompson Elizabeth D. , Hruban Ralph H. , Olive Kenneth P. , Feinberg Andrew P.
Published: June 2023

Variant and mutation calling
Supplementary Data from The m6A Reader YTHDF2 Promotes Bladder Cancer Progression by Suppressing RIG-I–Mediated Immune Response
Authors: Zhang Lei , Li Yuqing , Zhou Lingli , Zhou Houhong , Ye Liefu , Ou Tong , Hong Huaishan , Zheng Shiwen , Zhou Ziyu , Wu Kang , Yan Zeqin , Thiery Jean Paul , Cui Jun , Wu Song
Published: June 2023

Supplementary Data clean version
Data from Comprehensive DNA Methylation Analysis Indicates That Pancreatic Intraepithelial Neoplasia Lesions Are Acinar-Derived and Epigenetically Primed for Carcinogenesis
Authors: Lo Emily K.W. , Mears Brian M. , Maurer H. Carlo , Idrizi Adrian , Hansen Kasper D. , Thompson Elizabeth D. , Hruban Ralph H. , Olive Kenneth P. , Feinberg Andrew P.
Published: June 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is believed to arise from the accumulation of a series of somatic mutations and is also frequently associated with pancreatic intraepithelial neoplasia (PanIN) lesions. However, there is still debate as to whether the cell type-of-origin of PanINs and PDACs in humans is acinar or ductal. As cell type identity is maintained epigenetically, DNA methylation changes during pancreatic neoplasia can provide a compelling perspective to examine this question. Here, we performed laser-capture microdissection on surgically resected specimens from 18 patients to isolate, with high purity, DNA for whole-genome bisulfite sequencing from four relevant cell types: acini, nonneoplastic ducts, PanIN lesions, and PDAC lesions. Differentially methylated regions (DMR) were identified using two complementary analytical approaches: bsseq, which identifies any DMRs but is particularly useful for large block-like DMRs, and informME, which profiles the potential energy landscape across the genome and is particularly useful for identifying differential methylation entropy. Both global methylation profiles and block DMRs clearly implicated an acinar origin for PanINs. At the gene level, PanIN lesions exhibited an intermediate acinar-ductal phenotype resembling acinar-to-ductal metaplasia. In 97.6% of PanIN-specific DMRs, PanIN lesions had an intermediate methylation level between normal and PDAC, which suggests from an information theory perspective that PanIN lesions are epigenetically primed to progress to PDAC. Thus, epigenomic analysis complements histopathology to define molecular progression toward PDAC. The shared epigenetic lineage between PanIN and PDAC lesions could provide an opportunity for prevention by targeting aberrantly methylated progression-related genes.
Significance:
Analysis of DNA methylation landscapes provides insights into the cell-of-origin of PanIN lesions, clarifies the role of PanIN lesions as metaplastic precursors to human PDAC, and suggests potential targets for chemoprevention.
Data from Angiopoietin-2-dependent spatial vascular destabilization promotes T-cell exclusion and limits immunotherapy in melanoma
Authors: Park Ha-Ram , Shiva Anahita , Cummings Portia , Kim Seoyeon , Kim Sungsoo , Lee Eunhyeong , Leong Alessandra , Chowdhury Subrata , Shawber Carrie , Carvajal Richard , Thurston Gavin , An Joon Yong , Lund Amanda W. , Yang Hee Won , Kim Minah
Published: June 2023

Abstract
T cell position in the tumor microenvironment determines the probability of target encounter and tumor killing. CD8+ T cell exclusion from the tumor parenchyma is associated with poor response to immunotherapy, and yet the biology that underpins this distinct pattern remains unclear. Here we show that the vascular destabilizing factor angiopoietin-2 (ANGPT2) causes compromised vascular integrity in the tumor periphery, leading to impaired T cell infiltration to the tumor core. The spatial regulation of ANGPT2 in whole tumor cross-sections was analyzed in conjunction with T cell distribution, vascular integrity, and response to immunotherapy in syngeneic murine melanoma models. T cell exclusion was associated with ANGPT2 upregulation and elevated vascular leakage at the periphery of human and murine melanomas. Both pharmacological and genetic blockade of ANGPT2 promoted CD8+ T cell infiltration into the tumor core, exerting antitumor effects. Importantly, the reversal of T cell exclusion following ANGPT2 blockade not only enhanced response to anti-PD-1 immune checkpoint blockade therapy in immunogenic, therapy responsive mouse melanomas, but it also rendered non-responsive tumors susceptible to immunotherapy. Therapeutic response after ANGPT2 blockade, driven by improved CD8+ T cell infiltration to the tumor core, coincided with spatial TIE2 signaling activation and increased vascular integrity at the tumor periphery where endothelial expression of adhesion molecules was reduced. These data highlight ANGPT2/TIE2 signaling as a key mediator of T cell exclusion and a promising target to potentiate immune checkpoint blockade efficacy in melanoma.
Data from Prospective analysis reveals associations between carbohydrate intakes, genetic predictors of short-chain fatty acid synthesis, and colorectal cancer risk
Authors: Watling Cody Z. , Kelly Rebecca K. , Murphy Neil , Gunter Marc , Piernas Carmen , Bradbury Kathryn E. , Schmidt Julie A. , Key Timothy J. , Perez-Cornago Aurora
Published: June 2023

Abstract
Whole grain and fiber intakes may decrease the risk of colorectal cancer. The interplay between host genetic factors, colonization of specific bacteria, production of short-chain fatty acids (SCFA), and intake of whole grains and fiber could alter the protective role of carbohydrates against colorectal cancer. Here, we assessed intakes of types and sources of carbohydrates in 114,217 UK Biobank participants with detailed dietary data (2-5 24-hour dietary assessments), and a host polygenic score (PGS) was applied to categorize participants as high or low for intra-luminal microbial SCFA production, namely butyrate and propionate. Multivariable Cox proportional hazards models were used to determine the associations of carbohydrates and SCFA with colorectal cancer incidence. During a median follow-up of 9.4 years, 1,193 participants were diagnosed with colorectal cancer. Risk was inversely associated with intakes of non-free sugar and whole grain fiber. Evidence of heterogeneity was observed by the butyrate PGS; consuming higher amounts of whole grain starch was only associated with a lower risk of colorectal cancer in those with predicted high SCFA production. Similarly, in additional analyses utilizing the larger UK Biobank cohort (N=343,621) with less detailed dietary assessment, only individuals with a high genetically predicted butyrate production had a lower risk of colorectal cancer per 5 g/day intake of bread and cereal fiber. This study suggests that colorectal cancer risk varies by intake of carbohydrate types and sources, and the impact of whole grain intake may be modified by SCFA production.
Abstract A007: Modulation of HER2 as a mechanism for AR expression
Authors: Low Daniel K.Y. , Wilkinson Scott , King Isaiah M. , Trostel Shana Y. , Sowalsky Adam G.
Published: June 2023

Background: Intense neoadjuvant androgen deprivation therapy (inADT) is an emerging treatment paradigm for localized high-risk prostate cancer, but in certain patients a subset of tumors will recur after surgery. In tumors with endogenously low androgen receptor (AR) activity, expression of the EGFR family protein HER2 was enriched. We sought to investigate the role of HER2 in driving the proliferation of prostate cancer under androgen-depleted environments. We hypothesized that overexpression of HER2 would decrease AR activity, while its knockdown would conversely increase AR expression beyond baseline levels. Methods: The AR-expressing 22Rv1 and LNCaP prostate cancer cell lines were cultured and plated for transfection. HER2 overexpression was achieved using an exogenous HER2 (ERBB2) plasmid, while HER2 knockdown was performed using siRNA, alongside controls for both groups. Cell lysates were collected at 24-, 48-, and 72-hour time points. Western blotting was performed to examine HER2, AR, PSA, and actin expression. Results: Western blot analysis confirmed successful overexpression and knockdown of HER2, using an exogenous HER2 plasmid and siRNA, respectively. In 22Rv1 and LNCaP cells overexpressing HER2, AR (and AR-V7 in 22Rv1 cells) levels were decreased compared to the control cells. Conversely, 22Rv1 and LNCaP cells with knockdown of HER2 exhibited elevated AR expression. Biological replicates to confirm these findings are in progress. Additional studies will also examine the impact of HER2 signaling and activity on downstream pro-proliferative pathways. Conclusions: Manipulation of HER2 expression highlights a potential role of EGFR family proteins as a mechanism for prostate cancer growth in androgen-deprived environments. Future studies will validate this finding at the RNA level using qPCR and probe downstream targets of HER2 using western blotting. These preliminary findings have implications for the treatment of advanced tumors for which inADT is not a viable option. Targeting HER2 and its downstream signaling pathways represent an intriguing mechanism to overcome resistance to androgen deprivation therapy in newly-diagnosed, treatment-naïve patients.

Citation Format: Daniel K.Y. Low, Scott Wilkinson, Isaiah M. King, Shana Y. Trostel, Adam G. Sowalsky. Modulation of HER2 as a mechanism for AR expression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A007.
Abstract A077: MicroRNA drivers of resistance to androgen deprivation therapy in prostate cancer
Authors: Saunders Philippa C. , Fletcher Claire
Published: June 2023

INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signalling remains a key driver of growth. Androgen deprivation therapy (ADT) is therefore a first line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signalling inhibitors respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIALS AND METHODS: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Citation Format: Philippa C. Saunders, Claire Fletcher. MicroRNA drivers of resistance to androgen deprivation therapy in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A077.