bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrodynamic coupling for particle-based solvent-free membrane models
Authors: Sadeghi Mohsen , Noé Frank
Published: September 2021

The great challenge with biological membrane systems is the wide range of scales involved, from nanometers and picoseconds for individual lipids to the micrometers and beyond millisecond for cellular signaling processes. While solvent-free coarse-grained membrane models are convenient for large-scale simulations and promising to provide insight into slow processes involving membranes, these models usually have unrealistic kinetics. One major obstacle is the lack of an equally convenient way of introducing hydrodynamic coupling without significantly increasing the computational cost of the model. To address this, we introduce a framework based on anisotropic Langevin dynamics, for which major in-plane and out-of-plane hydrodynamic effects are modeled via friction and diffusion tensors from analytical or semi-analytical solutions to Stokes hydrodynamic equations. Using this framework, in conjunction with our recently developed membrane model, we obtain accurate dispersion relations for planar membrane patches, both free-standing and in the vicinity of a wall. We briefly discuss how non-equilibrium dynamics is affected by hydrodynamic interactions. We also measure the surface viscosity of the model membrane and discuss the affecting dissipative mechanisms.
Charge sensitivity of a cavity-embedded Cooper pair transistor limited by single-photon shot noise
Authors: Kanhirathingal S. , Brock B. L. , Rimberg A. J. , Blencowe M. P.
Published: September 2021

Using an operator scattering approach, we analyze the quantum dynamics of an ultrasensitive electrometer—a Cooper pair transistor embedded in a quarter-wave microwave cavity (cCPT). While the cCPT is inherently a tunable, strongly nonlinear system affording a diverse range of functionalities, we restrict our present analysis to a necessary first investigation of its linear charge sensing capabilities, limiting to low pump powers corresponding to an average cavity photon number of ≲1. Assuming realizable cCPT parameters [B. L. Brock et al., Phys. Rev. Applied 15, 044009 (2021)], and not including noise from the subsequent amplifier chain, we predict the fundamental, photon shot noise-limited charge sensitivity to be 0.12μe/Hz when the pumped cavity has an average of one photon and the cCPT is operated close to charge degeneracy. This is to be compared with a first reported charge sensitivity value of 14μe/Hz in the single-photon regime [B. L. Brock et al., arXiv:2102.05362 (2021)].
The total optical force exerted on black phosphorus coated dielectric cylinder pairs enhanced by localized surface plasmon
Authors: Ma Rui , Zhang Liangang , Liu Guidong , Wang Lingling , Lin Qi
Published: September 2021

Non-invasive manipulation and trapping of nanoparticles, molecules, and cells are essential in a variety of fields. The total optical force and near-field enhancement via localized surface plasmon resonance in the dielectric cylinder pairs coated with black phosphorus (DCPs-BP) are studied analytically and numerically in this work. In the DCPs-BP structure, the total optical force between the two cylinders can reach over 1000 pN/(mW μm). Specifically for the polystyrene particle captured in the center of the DCPs-BP structure, the optical trapping force up to 4000 pN/(mW μm) can be achieved. These results provide new avenues for the successful manipulation and capture of nanoscale particles.
Scattering of ultrashort laser pulses on plasmons in a Maxwellian plasma
Authors: Astapenko V. A. , Rosmej F. B. , Khramov E. S.
Published: September 2021

On the basis of equations obtained in the framework of second-order quantum-mechanical perturbation theory, the standard approach to the calculation of scattering radiation probability is extended to the case of ultrashort laser pulses. We investigate the mechanism of the appearance of plasmon peaks in the spectrum of the plasma form factor for different parameters of the problem. For the case in which scattering on plasmons dominates over scattering on electron density fluctuations caused by chaotic thermal motion, we derive analytical expressions describing the scattering probability of ultrashort laser pulses on plasmons. Together with this, we obtain a simple expression connecting the frequency of scattered radiation and the energy transmitted from the incident pulse to plasmon, and vice versa. In considering the scattering probability, our emphasis is on the dependence on the pulse duration. We assess in detail the trends of this dependence for various relations between pulse carrier frequency and plasmon energy.
The evolution of social parasitism inFormicaants revealed by a global phylogeny
Authors: Borowiec Marek L. , Cover Stefan P. , Rabeling Christian
Published: September 2021

Significance

Identifying the conditions associated with a life history transition from cooperative colony life to exploitative social parasitism is important for understanding how changes in behavior contribute to speciation. To explore the evolutionary origins of social parasitism, we reconstructed the evolutionary history ofFormicaants because half of all species are social parasites and all socially parasitic life history syndromes known from eusocial insects are represented in this genus. We demonstrate that social parasites evolved from an ancestor that lost the ability to establish new colonies independently and that highly specialized parasites can evolve from less complex social parasite syndromes. Our findings emphasize that social parasite syndromes readily originate in socially polymorphic organisms and evolved convergently across the ant phylogeny.
Therapeutic inhibition of USP9x-mediated Notch signaling in triple-negative breast cancer
Authors: Jaiswal Arushi , Murakami Kiichi , Elia Andrew , Shibahara Yukiko , Done Susan J. , Wood Stephen A. , Donato Nicholas J. , Ohashi Pamela S. , Reedijk Michael
Published: September 2021

Significance

There is clear and irrefutable evidence that the Notch developmental signaling pathway is an important driver in many cancers, specifically in breast cancer. However, because of the ubiquity of this pathway in normal tissues, therapeutics targeting Notch have been associated with significant deleterious side effects. Herein, we provide evidence that USP9x selectively drives Notch in breast cancer and that therapeutic USP9x inhibition prevents tumor progression without collateral damage to normal tissues.
A strong nonequilibrium bound for sorting of cross-linkers on growing biopolymers
Authors: Qiu Yuqing , Nguyen Michael , Hocky Glen M. , Dinner Aaron R. , Vaikuntanathan Suriyanarayanan
Published: September 2021

Significance

Understanding the connection between microscopic driving forces in biological systems and their emergent structures remains an outstanding challenge. We tackle this problem by deriving a fluctuation–response bound in the context of actin polymerization and bundling and verify its robustness far from equilibrium through simulation. Our results show how actin polymerization, molecular fluxes of cross-linker binding, and the morphology of the growing bundle are associated quantitatively; when the bound is saturated, it becomes a nonequilibrium linear-response relation. Molecular driving forces are difficult to measure directly in biological systems, and this work represents a first step toward estimating them from experimentally accessible quantities such as molecular fluxes and compositions.
Conversations about race in Black and White US families: Before and after George Floyd’s death
Authors: Sullivan J. Nicky , Eberhardt Jennifer L. , Roberts Steven O.
Published: September 2021

Significance

In the United States, Black households and White households have very different conversations about race. After the death of George Floyd, Black parents were even more likely to have such conversations with their children and to prepare their children to experience racial bias than they were before Floyd’s death. White parents were less likely to talk about being White and more likely to socialize their children toward colorblindness. In addition, White parents remained relatively unconcerned that their children may experience or perpetrate racial bias.
Dynamics of thin precursor film in wetting of nanopatterned surfaces
Authors: Anand Utkarsh , Ghosh Tanmay , Aabdin Zainul , Koneti Siddardha , Xu XiuMei , Holsteyns Frank , Mirsaidov Utkur
Published: September 2021

Significance

Wetting of rough surfaces is ubiquitous in nature and plays an important role in many natural and industrial processes. However, not much is known about the nanoscale details of the wetting. This gap in our understanding of wetting stems from a lack of suitable methods that enable direct imaging of interactions between liquids and nanoscale patterns. Here, using liquid-phase transmission electron microscopy, we directly image the wetting of dense arrays of patterned vertical nanopillars. Our observations show that wetting proceeds through the spreading of an ultrathin precursor liquid film followed by complete capillary-action–induced wetting of the nanopillars. Our observations that shed light on the details of wetting are critical for numerous applications in nanofabrication and surface engineering.
Testing a procedure to determine spatial proximity in semi-free-ranging macaque groups
Authors: Mármol Laura , Meunier Hélène , Dolado Ruth , Beltran Francesc S.
Published: September 2021

Individuals’ spatial position is affected by social factors. The majority of studies correlating spatial position and social factors have used methods with drawbacks. A more complete method was developed by Dolado & Beltran (2011) in captive animals. The present study aimed to apply a modified version of this method in two semi-free-ranging macaque groups. The proposed method divides group’s surroundings into different subareas, selecting different points in each subarea and calculating the coordinates of these points. We filmed each group and analyzed the videos using an activated time transition recording to determine the individuals’ coordinates. With these data, we calculated spatial variables, allowing us to obtain groups’ spatial patterns. The current method improves on previous procedures and could be applied to larger study areas and groups than the method of Dolado & Beltran (2011), thus representing a viable option for studying spatial distribution patterns in semi-free-ranging macaque groups.
Vertigo in childhood
Authors: Balzanelli Cristiano , Spataro Daniele , Redaelli de Zinis Luca Oscar
Published: September 2021

Objective

The current chapter will focus on epidemiological, etiological, and clinical data to optimize diagnostic and therapeutic approach of balance disorders in childhood.

Methods

Personal experience and analysis of the literature.

Results

The vestibular system is one of the first functioning systems of the human body. The vestibulo ocular reflex (VOR) is present at birth, and its values approaches those of a normal adult by 2 months of age. The vestibulospinal and vestibulocollic mechanism and the effectiveness of the vestibular system in postural control develop along a more protracted time course. Postural stability is mainly controlled by visual inputs in infants and children, whereas somatosensory inputs are primary in adults. Children begin to properly use somatosensory information at 3-6 years of age. Competence of the sensory systems to manage intersensory conflict is reached around 15 years of age.

Conclusion

Balance disorders, at any stage of a children neurodevelopment, can be very debilitating, worsening their basic daily activities and they can lead to psycho-neurological, affective, and behavioral dysfunctions.
Effect of multi-walled carbon nanotube on thermal decomposition, mechanical and heat-induced shape memory properties of crosslinked poly(vinyl alcohol)
Authors: Fan Leiming , Mei Xinliang , Zhang Juan , Zhu Jiaxing , Wang Xingsheng , Li Yanchun , Cai Wei
Published: September 2021

Shape memory polymers are attractive smart materials that have many promising applications in a wide variety of fields. Here the multi-walled carbon nanotube (MWCNT) was used to adjust the performance of crosslinked poly(vinyl alcohol) (PVA), which had acetal reaction with glutaraldehyde (GA). The thermal degradation, mechanical strength and shape recovery properties of PVA/MWCNT/GA membranes were investigated by thermogravimetry, differential scanning calorimetry, x-ray scattering, dynamic mechanical analysis, tensile test and thermal-stimulus shape memory recovery measurements. The MWCNT embedded in the crosslinked PVA matrix accelerated the breaking of C–O bonds. The mechanical strength and shape recovery properties of PVA/MWCNT/GA composites were tunable. As the MWCNT loading increase in crosslinked PVA matrix, the yield strength increased from 3.85 MPa to 10.21 MPa, breaking elongation decreased from 230% to 50%, the 100% shape recovery time decreased from 27 s to 16 s, respectively.
Single-beam multimodal nonlinear-optical imaging of structurally complex events in cell-cycle dynamics
Authors: Lanin A A , Chebotarev A S , Kelmanson I V , Pochechuev M S , Fetisova E S , Bilan D S , Shevchenko E K , Ivanov A A , Fedotov A B , Belousov V V , Zheltikov A M
Published: September 2021

We demonstrate a multimodal nonlinear-optical imaging that combines second- and third-harmonic generation (SHG and THG) with three-photon-excited fluorescence (3PEF) as a means to resolve fine details of the cell structure and trace its transformations throughout structurally complex episodes of cell-cycle dynamics, including the key stages and signatures in cell division. When zoomed in on cell mitosis, this technique enables a high-contrast multimodal imaging of intra- and extracellular signatures of cell division, detecting, via a multiplex, 3PEF/SHG/THG readout, a remarkable diversity of shapes, sizes, and symmetries in a truly single-beam setting, with no need for beam refocusing or field-waveform re-adjustment.
Made in Manchuria: The Transnational Origins of Socialist Industrialization in Maoist China
Authors: Hirata Koji
Published: September 2021

With its high concentration of state-owned enterprises (SOEs) in heavy industry, Manchuria (Northeast China) functioned as a symbol of the “socialist industrialization” in the early years of the People’s Republic of China (PRC, 1949–). Many Manchurian SOEs nevertheless originated as Japanese colonial enterprises founded before 1945. Drawing on archives and interviews in Chinese, Japanese, English, and Russian, I trace industrial Manchuria’s transformation before and after the Communist Revolution with a particular focus on Anshan Iron and Steel Works (Angang). I argue that the industrial legacies of imperial Japan and Nationalist China in Manchuria facilitated China’s transition to a Soviet-style socialist planned economy under Mao Zedong’s leadership (1949–76). The early PRC developed a new system of socialist industrialization by simultaneously learning from Soviet economic planning and deploying physical assets, human resources, and economic institutions left by the Japanese and the Nationalists. My findings expand on recent scholarship on the pre-Communist origins of the early PRC by elucidating the significance of the Japanese influence. More broadly, I also argue that China’s socialist industrialization was decisively influenced by the global spread of state-directed developmental visions during the interwar period, thereby demonstrating the fundamental interconnectedness between capitalism and socialism in the twentieth century.
DKK1 suppresses WWP2 to enhance bortezomib resistance in multiple myeloma via regulating GLI2 ubiquitination
Authors: Zhang Qiguo , Gong Wenyu , Wu Hongyan , Wang Jing , Jin Qichuan , Lin Chun , Xu Shiyun , Bao Wenqiang , Wang Yin , Wu Jing , Feng Shanshan , Zhao Changzhi , Chen Bing , Liu Zhiqiang
Published: September 2021

Bortezomib-based chemotherapy represents the most prevalent regimens for multiple myeloma (MM), whereas acquired drug resistance remains a major obstacle. Myeloma cells often produce excessive amount of dickkopf-1 (DKK1), giving rise to myeloma bone disease. However, it remains obscure about the effects and mechanisms of DKK1 in the progression and bortezomib responsiveness of MM cells. In the current study, we found WWP2, an E3 ubiquitin-protein ligase, was downregulated in the bortezomib-resistant cells along with high expression of DKK1. Further investigation revealed that WWP2 was a direct target of Wnt/β-catenin signaling pathway, and DKK1 suppressed the expression of WWP2 via canonical Wnt signaling. We further identified that WWP2 mediated the ubiquitination and degradation of GLI2, a main transcriptional factor of the Hedgehog (Hh) pathway. Therefore, DKK1-induced WWP2 downregulation improved GLI2 stability and activation of Hh signaling pathway, contributing to the resistance to bortezomib of MM cells. Clinical data also validated that WWP2 expression was associated with the treatment response and clinic outcomes of MM patients. WWP2 overexpression restricted MM progression and enhanced cell sensitivity to bortezomib treatment in vitro and in vivo. Taken together, our findings demonstrate that DKK1 facilitates the generation of bortezomib resistance in MM via downregulating WWP2 and activating Hh pathway. Thus, the manipulation of DKK1–WWP2–GLI2 axis might sensitize myeloma cells to proteasome inhibitors.
Low Environmental Temperature Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Golden Syrian Hamsters
Authors: Chan Jasper Fuk Woo , Poon Vincent Kwok Man , Chan Chris Chung Sing , Chik Kenn Ka Heng , Tsang Jessica Oi Ling , Zou Zijiao , Chan Chris Chun Yiu , Lee Andrew Chak Yiu , Li Can , Liang Ronghui , Cao Jianli , Tang Kaiming , Yuen Terrence Tsz Tai , Hu Bingjie , Huang Xiner , Chai Yue , Shuai Huiping , Luo Cuiting , Cai Jian Piao , Chan Kwok Hung , Sridhar Siddharth , Yin Feifei , Kok Kin Hang , Chu Hin , Zhang Anna Jinxia , Yuan Shuofeng , Yuen Kwok Yung
Published: September 2021

Background

The effect of low environmental temperature on viral shedding and disease severity of Coronavirus Disease 2019 (COVID-19) is uncertain.

Methods

We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21°C), low (12–15°C), and high (30–33°C) temperature after challenge by 105 plaque-forming units of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results

The nasal turbinate, trachea, and lung viral load and live virus titer were significantly higher (~0.5-log10 gene copies/β-actin, P < .05) in the low-temperature group at 7 days postinfection (dpi). The low-temperature group also demonstrated significantly higher level of tumor necrosis factor-α, interferon-γ (IFN-γ), interleukin-1β, and C-C motif chemokine ligand 3, and lower level of the antiviral IFN-α in lung tissues at 4 dpi than the other 2 groups. Their lungs were grossly and diffusely hemorrhagic, with more severe and diffuse alveolar and peribronchiolar inflammatory infiltration, bronchial epithelial cell death, and significantly higher mean total lung histology scores. By 7 dpi, the low-temperature group still showed persistent and severe alveolar inflammation and hemorrhage, and little alveolar cell proliferative changes of recovery. The viral loads in the oral swabs of the low-temperature group were significantly higher than those of the other two groups from 10 to 17 dpi by about 0.5–1.0 log10 gene copies/β-actin. The mean neutralizing antibody titer of the low-temperature group was significantly (P < .05) lower than that of the room temperature group at 7 dpi and 30 dpi.

Conclusions

This study provided in vivo evidence that low environmental temperature exacerbated the degree of virus shedding, disease severity, and tissue proinflammatory cytokines/chemokines expression, and suppressed the neutralizing antibody response of SARS-CoV-2-infected hamsters. Keeping warm in winter may reduce the severity of COVID-19.
Super high-flux membrane dialyzers improve mortality in patients on hemodialysis: a 3-year nationwide cohort study
Authors: Abe Masanori , Masakane Ikuto , Wada Atsushi , Nakai Shigeru , Nitta Kosaku , Nakamoto Hidetomo
Published: September 2021

Introduction

In Japan, dialyzers are classified based on β2-microglobulin clearance. Type I dialyzers are classified as low-flux dialyzers (<10 mL/min clearance), type II and III as high-flux dialyzers (≥10 to <30 mL/min and ≥30 to <50 mL/min clearance, respectively), and type IV and V as super high-flux dialyzers (≥50 to <70 mL/min and ≥70 mL/min clearance, respectively). Super high-flux dialyzers are commonly used, but their superiority over low-flux dialyzers is controversial.

Methods

In this nationwide prospective cohort study, we analyzed Japanese Society for Dialysis Therapy Renal Data Registry data collected at the end of 2008 and 2011. We enrolled 242,467 patients on maintenance hemodialysis and divided them into five groups by dialyzer type. We assessed the associations of each dialyzer type with 3-year all-cause mortality using Cox proportional hazards models and performed propensity score matching analysis, adjusting for potential confounders.

Results

By the end of 2011, 53,172 (21.9%) prevalent dialysis patients had died. Mortality significantly decreased according to dialyzer type. Hazard ratios (HRs) were significantly higher for type I, II and III compared with type IV (reference) after adjustment for basic factors and further adjustment for dialysis-related factors. HR was significantly higher for type I, but significantly lower for type V, after further adjustment for nutrition- and inflammation-related factors. These significant findings were also evident after propensity score matching.

Conclusions

Hemodialysis using super high-flux dialyzers might reduce mortality. Randomized controlled trials are warranted to clarify whether these type V dialyzers can improve prognosis.
A Novel Approach to Adaptive Resource Allocation for Energy Saving in Reconfigurable Heterogeneous Networks
Authors: Nabipour Mohammad , Momen Amir Reza
Published: September 2021

The dense deployment of small cell networks is a key feature of next generation mobile networks aimed at providing the necessary capacity increase. Wireless heterogeneous networks are created by combining several radio access technologies, each with its own potentials, capabilities and limitations. In these networks, providing real-time services with quality assurance is essential. For effective use of radio resources, the Radio Resource Management method was introduced which its performance and efficiency is better than the control of independent radio resources in any radio access technology. In this paper, we introduced a novel approach to select the most effective radio access technologies by taking into account some performance parameters like the type of service, users’ distribution pattern and the cost of the services. It also optimizes the handover relations between macrolayer and small cells. The proposed approach is a self-optimizing model can be employed to control resources and improve performance indices associated with mobile networks without human interference by only relying on network intelligence. In order to maximize the network performance, we applied the dynamic backhauling technique to analyze the uplink signaling data which increased the validity level of the decision-making process. Based on the extracted semantic information, the network decision-making engine is able to adjust the network parameters and efficiently allocate the resources. The numerical results exhibit considerable power saving for different traffic models in addition to reduce the rate of vertical handovers. The results also show increase the network throughput by up to 30%.
Multi-Keyword Ranked Searchable Encryption with the Wildcard Keyword for Data Sharing in Cloud Computing
Authors: Liu Jinlu , Zhao Bo , Qin Jing , Zhang Xi , Ma Jixin
Published: September 2021

Multi-keyword ranked searchable encryption (MRSE) supports multi-keyword contained in one query and returns the top-k search results related to the query keyword set. It realized effective search on encrypted data. Most previous works about MRSE can only make the complete keyword search and rank on the server-side. However, with more practice, users may not be able to express some keywords completely when searching. Server-side ranking increases the possibilities of the server inferring some keywords queried, leading to the leakage of the user’s sensitive information. In this paper, we propose a new MRSE system named ‘multi-keyword ranked searchable encryption with the wildcard keyword (MRSW)’. It allows the query keyword set to contain a wildcard keyword by using Bloom filter (BF). Using hierarchical clustering algorithm, a clustering Bloom filter tree (CBF-Tree) is constructed, which improves the efficiency of wildcard search. By constructing a modified inverted index (MII) table on the basis of the term frequency-inverse document frequency (TF-IDF) rule, the ranking function of MRSW is performed by the user. MRSW is proved secure under adaptive chosen-keyword attack (CKA2) model, and experiments on a real data set from the web of science indicate that MRSW is efficient and practical.
It is time to mate: population-level plasticity of wild boar reproductive timing and synchrony in a changing environment
Authors: Brogi Rudy , Merli Enrico , Grignolio Stefano , Chirichella Roberta , Bottero Elisa , Apollonio Marco
Published: September 2021

On a population level, individual plasticity in reproductive phenology can provoke either anticipations or delays in the average reproductive timing in response to environmental changes. However, a rigid reliance on photoperiodism can constraint such plastic responses in populations inhabiting temperate latitudes. The regulation of breeding season length may represent a further tool for populations facing changing environments. Nonetheless, this skill was reported only for equatorial, nonphotoperiodic populations. Our goal was to evaluate whether species living in temperate regions and relying on photoperiodism to trigger their reproduction may also be able to regulate breeding season length. During 10 years, we collected 2,500 female reproductive traits of a mammal model species (wild boar Sus scrofa) and applied a novel analytical approach to reproductive patterns in order to observe population-level variations of reproductive timing and synchrony under different weather and resources availability conditions. Under favorable conditions, breeding seasons were anticipated and population synchrony increased (i.e., shorter breeding seasons). Conversely, poor conditions induced delayed and less synchronous (i.e., longer) breeding seasons. The potential to regulate breeding season length depending on environmental conditions may entail a high resilience of the population reproductive patterns against environmental changes, as highlighted by the fact that almost all mature females were reproductive every year.
100 TOTAL LYMPHOCYTES COUNT (TLC) PREDICTS THE OVERALL SURVIVAL AFTER CHEMORADIOTHERAPY IN ESOPHAGEAL CARCINOMA PATIENTS
Authors: Nishida Masato , Sato Shinsuke , Higashizono Kazuya , Taki Yusuke , Nagai Erina , Wataanbe Masaya , Ohata Ko , Kanemoto Hideyuki , Oba Noriyuki
Published: September 2021

Lymphocytes play a critical role in the host immune system, and a decrease in number of lymphocytes, caused by malnutritional status and chemoradiotherapy (CRT) leads to immunosuppression. Immunosuppression could enhance the cancer development and progression. Previous studies demonstrated that lymphopenia was associated with worse prognosis in the pancreatic, lung, head and neck, and rectal cancer, but little is known about esophageal cancer.

Methods

There were 298 patients of esophageal malignant tumors, who had been initially treated with chemoradiotherapy (CRT) between January, 2007 and December, 2018. The total lymphocyte counts (TLC) before CRT and the nadir value during 6 weeks after CRT along with other clinical and treatment characteristics of these 298 patients, were retrospectively evaluated in relevance with the overall survival (OS) after CRT.

Results

The median TLC before and after CRT were 1469 (range 456–4710)/mm3 and 354 (range 21–1500)/mm3, respectively. When the patients were stratified with the threshold value of 1500/mm3 of pretreatment TLC, the Log-Rank test showed significant difference in OS between these 2 groups (OS 48.7% vs 36.6%, p = 0.011). In addition, the CTCAE grade of lymphopenia exceeding 3 after CRT was associated with worse OS even in the group with pretreatment TLC level more than 1500/mm3. The multivariate analysis showed that the significant prognostic factors of OS were cN, cM, additional esophagectomy and pretreatment TLC.

Conclusion

The decease of pretreatment TLC was significantly associated with worse OS when the patients of esophageal cancer were initially treated with CRT.
155 A META-ANALYSIS OF EFFICACY AND SAFETY OF ANTI-BODIES TARGETING PD-1 IN TREATMENT OF ADVANCED ESOPHAGEAL CANCER
Authors: Wang Feng , Lu Yao , Meng Xiangrui , Fan Qingxia
Published: September 2021

Systemic chemotherapy is the first choice for patients with advanced esophageal cancer. However, due to drug resistance and dose-limiting toxicity, a large number of patients in China have not been treated. A novel therapy based on programed death 1 (PD-1) inhibitors has been proved to be effective in advanced esophageal cancer.This article is a meta-analysis aiming to systematically evaluate the efficacy and safety of anti-PD-1 therapy in patients with esophageal cancer.

Methods

Data were collected from eligible studies searched from PubMed, Web of Science, Cochrane Library and Embase. Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1 inhibitors versus chemotherapy, and pooled odds ratio (OR) was calculated for objective response rate (ORR). The analysis among patients tested with different PD-1 status was also performed to figure out the relationship between PD-1 status and efficacy of anti-PD-1 therapy. The OR for occurrence of treatment-related adverse effect was calculated to assess the safety of anti-PD-1 therapy.

Results

A total of 8 studies were analyzed. Compared with patients with chemotherapy, patients with anti-PD-1 therapy had a significant improvement in OS (HR = 0.80, 95% CI: 0.70–0.91, P = 0.001), but no significant relationship was observed in ORR (HR = 1.87, 95% CI: 0.82–4.25, P = 0.13) and PFS (HR = 0.94, 95% CI: 0.70–1.26, P = 0.67). A similar result was observed in esophageal squamous cell carcinoma (ESCC). The PD-L1 status has no obvious connection with the efficacy of anti-PD-1 therapy. The incidence of grade 3 to 5 treatment-related adverse effect(AE) in anti-PD-1therapy was distinctly lower than that in chemotherapy, but there is no statistical difference in all treatment-related AE.

Conclusion

Anti-PD-1 therapy significantly prolonged the OS when compared with chemotherapy, while no significantly difference in PFS and ORR for the population of esophageal cancer, ESCC， PD-L1 positive. Based on the analysis of grade 3 to 5 treatment-related adverse effect events, a lower risk was associated with the anti-PD-1 therapy versus chemotherapy.
165 CLINICAL IMPACT OF PREOPERATIVE SERUM P53 ANTIBODY TITERS IN 1,487 PATIENTS WITH ESOPHAGEAL CARCINOMA: A MULTI-INSTITUTIONAL STUDY
Authors: Suzuki Takashi , Yajima Satoshi , Okamura Akihiko , Yoshida Naoya , Taniyama Yusuke , Murakami Kentarou , Okura Yu , Nakajima Yasuaki , Yagi Kouichi , Fukuda Takashi , Ogawa Ryo , Hoshino Isamu , Tanaka Yusaku , Narumiya Kosuke , Tsubosa Yasuhiro , Soma Daisuke , Shimada Hideaki
Published: September 2021

Although previous reports showed clinicopathological and diagnostic significance of serum p53 antibody in esophageal squamous cell carcinoma, all those reports analyzed only 100 to 200 patients at single institute. This study was designed as a multi-institutional study promoted by the Japan Esophageal Society to elucidate the clinical significance of serum p53 antibody in esophageal cancer treatment.

Methods

A total of 1,487 patients, from 15 hospitals of Japan, with esophageal carcinoma surgically treated between 2008 and 2016 were enrolled in this retrospective study. We used 1.30 U/ml as a cutoff for classifying patients into positive and negative groups. And we attempted to analyze only positive cases. A receiver operating characteristic curve was constructed to assess serum p53 antibody cutoff levels to differentiate poor prognosis. We used 9.82 U/ml as a cutoff for classifying patients into low and high groups. Univariate and multivariate analyses were used to evaluate the clinicopathological and prognostic significance of pretreatment level of serum p53 antibody.

Results

There were significant relationships between serum p53 antibody level and tumor depth (p = 0.002), nodal status (p = 0.027) and pathological stage (p = 0.002). The positive serum p53 antibody group had a no significantly worse overall survival than that of the negative group (p = 0.699). The high serum p53 antibody group had a significantly worse overall survival than that of the low group (p = 0.024). However, the difference was not significant in the multivariate analysis (p = 0.137).

Conclusion

Although high level (>9.82 U/ml) of pretreatment serum p53 antibody might be associated with poor prognosis for patients with esophageal cancer, high serum p53 antibody was not an independent risk factor.
215 LOCATION OF ANASTOMOSIS BEHIND THE STERNOCLAVICULAR JOINT INCREASES THE INCIDENCE OF ANASTOMOTIC STENOSIS IN RETROSTERNAL RECONSTRUCTION AFTER ESOPHAGECTOMY
Authors: Kurahashi Yasunori , Hojo Yudai , Nakamura Tatsuro , Kumamoto Tsutomu , Nakanishi Yasutaka , Ishida Yoshinori , Shinohara Hisashi
Published: September 2021

Anastomotic stenosis after esophagectomy is a major cause of long-term morbidity because it leads to poor dietary intake and malnutrition that markedly reduces quality of life. The aim of this study was to test the hypothesis that the risk of anastomotic stenosis is higher when the anastomosis is located behind the sternoclavicular joint than when it deviates from the sternoclavicular joint.

Methods

Among 226 patients who underwent esophagectomy between April 2010 and March 2019, we selected 114 patients who underwent retrosternal reconstruction using a gastric conduit for this study. They were classified into two groups according to the location of the anastomosis as determined by postoperative computed tomography scans: anastomosis located behind the sternoclavicular joint (group B; n = 71) and anastomosis deviated from the joint (group D; n = 43). The primary endpoint was the difference in the incidence of anastomotic stenosis between the two groups. Whether the occurrence of anastomotic leak affected the likelihood of anastomotic stenosis was also investigated.

Results

The incidence of anastomotic stenosis was significantly higher in group B than in group D (71.8% [n = 51] vs 18.6% [n = 8]; p < 0.0001). The incidence of stenosis in patients who developed an anastomotic leak was significantly higher in group B than in group D (88.0% vs 41.7%; p = 0.0057), although the findings were similar in patients who did not develop an anastomotic leak (63.0% and 9.7%, respectively; p < 0.0001).

Conclusion

There is an increased risk of anastomotic stenosis independent of anastomotic leak when the anastomosis is located behind the sternoclavicular joint in patients who undergo retrosternal reconstruction with a gastric conduit after esophagectomy.
287 OUTCOMES OF DEFINITIVE CHEMORADIOTHERAPY IN LONG SEGMENT ESOPHAGEAL CANCERS FROM A TERTIARY CANCER CENTRE IN INDIA
Authors: Agarwal Jaiprakash , Tibdewal Anil , Johnny Carlton , Chopade Pradnya , Mummudi Naveen , Mhatre Ritesh , Kinhikar Rajesh , Noronha Vanita , Prabhash Kumar
Published: September 2021

Definitive chemoradiotherapy (CTRT) is the standard of care for unresectable esophageal cancer. Long segment esophageal primary disease makes it challenging to deliver radiation doses needed to achieve good local control without exceeding normal tissue tolerance to the surrounding organs at risk (OAR). We report our experience and outcomes of such patients where the RT doses were reduced from our institutional standard of 63Gy to 50.4Gy.

Methods

Between Jan 2017 and Dec 2019, 30/232 consecutive esophageal cancer patients were identified with long segment disease that required dose reduction from 63 to 50.4Gy and were included in this analysis. For this study, we divided nodal regions by their location into cervical, mediastinal, and gastro-hepatic. We generated and compared dosimetric parameters of the standard dose (63Gy) plan with that of treated low-dose plan (50.4Gy) using paired t-test. We also evaluated the patterns of recurrence and have reported them as local relapse (LR), loco-regional relapse (LRR), and distant metastases (DM).

Results

The median age was 55.5 years; 16 (53.3%) were males and 28 (93.3%) had squamous carcinoma. Single nodal site was involved in 6(20%), 2 sites in 20(66.7%) and 3 sites in 4 (13.3%). Median GTV and PTV length were 7.9 cm (IQR:6.4–9.7 cm) and 18.8 cm (IQR:14.08–22.31 cm) respectively. Median OAR doses with standard Vs treated plan achieved were: Total lung V20 and V5:28 Vs 22.14% (p = 0.00), and 81 Vs 70.5% (p = 0.005) respectively, and heart V20:70.92% Vs 64.7% (p = 0.000). No patients experienced ≥grade2 lung toxicity. After a median follow up of 8.4 months, 3 patients experienced LRR and 1 developed DM.

Conclusion

Treatment of long segment esophageal cancers warrants dose reduction to avoid higher doses to OAR like lung and heart. Early loco-regional and distant failures suggest need for improved treatment strategies or dose escalation with more conformal techniques like proton therapy. Longer follow-up is necessary to assess the median LR, LRR rates and overall survival for this reduced dose group as compared to the standard dose group.
309 ASSOCIATION BETWEEN CERVICAL ANASTOMOSIS METHODS AND ANASTOMOSIS STRICTURE AFTER ESOPHAGECTOMY FOR CANCER
Authors: Suzuki Akihiro
Published: September 2021

Esophagectomy with three-field lymph node dissection is the most important part of advanced esophageal cancer therapy, especially for squamous cell carcinoma (SCC) patients. After esophagectomy, cervical anastomosis with gastric tube is required. However, some patients suffer anastomotic stenosis and require endoscopic balloon dilations. In this study, we investigated the relationship between cervical anastomosis methods and anastomosis stricture after esophagectomy for cancer patients.

Methods

Patients with esophageal cancer undergoing radical esophagectomy with cervical anastomosis were identified from the prospectively maintained database at our institution. From 2013 to 2019, 28 patients received esophagectomy with cervical lymph node dissection in our institution. Association between anastomotic methods, linear stapler vs circular stapler, and other factors (patient characteristics, surgical complications including anastomotic stenosis, and length of postoperative stay) were analyzed.

Results

Their average age was 63.3 years. Males and SCC cases predominated. Thirteen patients (46%) received cervical anastomosis with the circular stapler (Group C), and 11 patients (39%) received treatment with the linear stapler (Group L).

None of the following variables were significant different between the two methods: preoperative chemotherapy (53.8% in group C vs. 45.5% in group L; p = 0.58), length of hospital stay (25.8 vs. 20.7 days; p = 0.15), pulmonary complications (16.7% vs. 0.0%; p = 0.36), and anastomotic leakage (33.3% vs. 9.1%; p = 0.24). However, the rate of anastomotic stenosis without malignancies was significantly higher in group C patients (66.7% vs. 0%, p < 0.01).

Conclusion

Cervical anastomosis with the linear stapler may be safer and associated with a lower stenosis rate than with the circular stapler. In future, cervical anastomosis with linear stapler after mediastinoscopic esophagectomy would be better for not only esophageal SCC patients but also esophagogastric junction adenocarcinoma patients with pulmonary complications.
351 SINGLE-PORT MINIMALLY INVASIVE ESOPHAGECTOMY TO TREAT ESOPHAGEAL CANCER: EXPERIENCE OF 144 CASES
Authors: Lee Jang-Ming , Ke-Cheng Chen , Mong-Wei Lin , Pei-Wen Yang , Pei-Ming Huang
Published: September 2021

Single-incision thoracoscopic and laparoscopic procedures has have been applied in treating various diseases. However, it is limited in literature for such procedures used in treating esophageal cancer.

Methods

Minimally invasive esophagectomy (MIE) with a single-incision approach in the thoracoscopic and laparoscopic procedures was attempted in 144 patients with esophageal cancer.

Results

There was 96 patients underwent a McKeown procedure and 48 an Ivor Lewis procedure repectively. The mean ventilator usage of the patients after surgery was 0.3 ± 0.6 days, the mean ICU stay was 7.42 ± 17.15 days, and the mean number of dissected lymph nodes was 43.5 ± 21.8. There 11 patients suffered from postoperative complications, including 3 pulmonary complications, 4 anastomotic leakage and 4 vocal cord palsy. There are no 30-day mortality, however, there were one patient died from ARDS 40 days after surgery.

Conclusion

Single-port MIE seems to be a feasible option for treating patients with esophageal cancer, which offers an acceptable perioperative surgical outcome. However, the long-term survival results of the patients requires to be follow-up in the future.
385 MIR-24-3P REGULATES CDX2 DURING THE PROCESS OF INTESTINALIZATION OF THE CARDIAC-TYPE EPITHELIUM IN A HUMAN MODEL OF BARRETT’S ESOPHAGUS
Authors: Pera Manuel , Garrido Marta , Gil Gabriel , Fassan Matteo , Climent Marta , Nonell Lara , Anglada Roger , Iglesias Mar , Guzzardo Vicenza , Borga Chiara , Grande Luis , Bolós Carme
Published: September 2021

Cardiac-type epithelium has been proposed as an intermediate stage between normal squamous epithelium and intestinal metaplasia in the development of Barrett’s esophagus. Deregulation of certain miRNAs and their effects on CDX2 expression might contribute to the intestinalization process of cardiac-type epithelium. The aim of this study was to identify miRNAs differentially expressed between CDX2 positive and negative glands of Barrett’s esophagus and to examine the function of specific miRNAs on the regulation of CDX2.

Methods

miRNA expression profiling using OpenArrayTM analysis in microdissected cardiac-type glands with and without fully CDX2 expression was performed in biopsies from patients who developed cardiac-type epithelium in the remnant esophagus after esophagectomy. Data were validated using real-time PCR in esophageal adenocarcinoma cell lines and in situ and real-time PCR miRNA/CDX2/MUC2 co-expression analysis in cardiac-type mucosa samples. The effect of miR-24-3p precursor transfection on CDX2 expression was assessed in the esophageal adenocarcinoma cell lines FLO-1 and KYAE-1.

Results

CDX2 positive glands were characterized by an unique miRNA profile with a significant downregulation of miR-24-3p, miR-520e-3p, miR-548a-1, miR-597-5p, miR-133a-3p, miR-30a-5p, miR-638, miR-625-3p, miR-1255b-1, miR-1260a and upregulation of miR-590 (Figure 1A). miRNA-24-3p was identified as potential regulator of CDX2 gene expression in three bioinformatics algorithms, and this was confirmed in esophageal adenocarcinoma cell lines (Figure 1C). Furthermore, miR-24-3p expression negatively correlates with CDX2 in cardiac-type mucosa samples with different stages of mucosal intestinalization (Figure 1B).

Conclusion

These results imply that miRNA-24-3p directly targets CDX2, and downregulation of miRNA-24-3p is associated with the acquisition of an intestinal phenotype in cardiac-type epithelium.
476 ICG FLUORESCENCE IN IDENTIFICATION OF THORACIC DUCT
Authors: Thammineedi Subramanyeshwar Rao
Published: September 2021

Not applicable because it is a Video presentation.

Methods

Not applicable because it is a Video presentation.

Results

Not applicable because it is a Video presentation.

Conclusion

Not applicable because it is a Video presentation.

Video

Video shows visualisation of thoracic duct during esophagectomy by real-time fluorescent imaging. Intraoperative fluorescence lymphangiography was performed by injecting 2.5 mg of ICG into small bowel mesentery at Laparoscopy.At Thoracoscopy, Thoracic duct was visualised after 65 minutes. ICG fluorescence lymphangiography provides a feasible, reliable and real-time imaging of thoracic duct during esophagectomy, thereby potentially reducing thoracic duct injuries. https://drive.google.com/open?id=1ROGQ1K-yWkO-B3oSk8dGbsRu4iCKGfJq.
551 INCREASED POSTOPERATIVE MORBIDITY AFTER TOTALLY MINIMALLY INVASIVE ESOPHAGECTOMY FOR CANCER IN ELDERLY PATIENTS
Authors: Baranov Nikolaj , Baranov Nikolaj , Van Workum Frans , Rosman Camiel
Published: September 2021

The incidence of elderly patients with esophageal cancer is increasing. The aim of this study is to compare postoperative outcomes after esophagectomy between elderly patients and younger patients and to compare outcomes after totally minimally invasive esophagectomy (TMIE) and open esophagectomy (OE) in these age groups.

Methods

Data was retrieved from the Dutch Upper Gastrointestinal Cancer Audit (DUCA), a national surgical outcome registry. The primary outcome parameter was severe complications, defined as Clavien Dindo ≥3. Secondary outcome parameters were postoperative complications, reintervention rate, length of hospital stay and mortality. Outcome parameters were compared between patients aged ≥75 years and < 75 years and between TMIE and OE in these age groups. We adjusted for the following casemix parameters: gender, Charlson Co-morbidity Index score ASA score and neoadjuvant therapy. A sensitivity analysis was performed with different age groups: <65, 65–69, 70–74, 75–79 and ≥ 80 years.

Results

Of all 5539 included patients 14.0% were aged ≥75 years and 86.0% were aged <75 years. Severe complications were observed more frequently in the elderly group compared to the younger group (RR = 1.15 [1.04–1.27], p = 0.007). Interestingly, there was an increased risk of severe complications after TMIE in both the elderly group (RR = 1.50 [1.19–1.90], p = 0.001) and the younger group (RR = 1.41 [1.28–1.56], p < 0.001). No difference in mortality between TMIE and OE was found. Sensitivity analyses of TMIE compared to OE across all age groups showed increased risk of severe complications. Adjustment for casemix for all analysis did not change the results.

Conclusion

Severe complications after esophagectomy occur more frequently in elderly compared to younger patients. TMIE in elderly patients did not result in less morbidity and was in fact associated with more severe complications compared to OE across all age groups, which may be due to a learning curve effect.