bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Lower-Limb Exercise on Pain Management of the Patients Undergoing Posterior Lumbar Fusion Surgery: A Retrospective Case-Control Study
Authors: Wu Tong , Ye Yong
Published: December 2021

Purpose. The purpose of this study is to investigate the clinical effect of lower-limb exercise, when combined with celecoxib, on pain management of patients undergoing posterior lumbar fusion surgeries. Methods. The patients undergoing posterior lumbar fusion surgeries between 01/2018 and 06/2021 were retrospectively identified, with their data collected. After surgery, some patients took celecoxib for analgesia (celecoxib group, 200 mg/day) while the others took celecoxib together with lower-limb exercise (combined group, celecoxib-200 mg/day). On postoperative days (POD) 1, 3, 7, and 14, data were collected and analyzed regarding the following items: patient satisfaction, lower-limb muscle force, lumbar JOA score (29 points), Oswestry Disability Index (ODI), and visual analog scale (VAS) score. Results. A total of 225 participants were included in this study. Specifically, 120 cases were admitted into in the celecoxib group and 105 were included in the combined group. Comparisons of baseline data did not indicate any difference between the combined group and the celecoxib group. Data analysis showed that patient satisfaction in the combined group was significantly higher than the celecoxib group on POD 3, 7, and 14, respectively (all

p
<
0.001

). Moreover, the combined group had less VAS score compared with the celecoxib group on POD 3, 7, and 14, respectively (all

p
<
0.01

). In addition, lower-limb muscle force in the combined group was significantly stronger than that in the celecoxib group on POD 3 and POD 7, respectively (both

p
<
0.01

). Furthermore, the combined group achieved less ODI score than the celecoxib group on POD 3, 7, and 14, respectively (all

p
<
0.05

). Comparisons of the lumbar JOA score did not suggest any statistical difference during the whole follow-up period. Conclusions. In conclusion, postoperative lower-limb rehabilitation exercise can help to release pain after lumbar fusion surgeries. Additionally, postoperative lower-limb exercise can facilitate the recovery of lower-limb muscle force, as well as improving patient satisfaction.
“Avatar to Person” (ATP) Virtual Human Social Ability Enhanced System for Disabled People
Authors: Guo Zichun , Wang Zihao , Jin Xueguang
Published: December 2021

How to make communication more effective has been underlined unprecedentedly in the artificial intelligence (AI) era. Nowadays, with the improvement of affective computing and big data, people have generally adapted to construct social networks relying on social robots and smartphones. Although the technologies above have been widely discussed and used, researches on disabled people in the social field are still very limited. In particular, facial disabled people, deaf‐mutes, and autistic patients are still meeting great difficulty when interacting with strangers using online video technology. This project creates a virtual human social system called “Avatar to Person” (ATP) based on artificial intelligence and three‐dimensional (3D) simulation technology, with which disabled people can complete tasks such as “virtual face repair” and “simulated voice generation,” in order to conduct face‐to‐face video communication freely and confidently. The system has been proven effective in the enhancement of the sense of online social participation for people with disabilities through user tests. ATP is certain to be a unique area of inquiry and design for disabled people that is categorically different from other types of human‐robot interaction.
A High-Order Melnikov Method for Heteroclinic Orbits in Planar Vector Fields and Heteroclinic Persisting Perturbations
Authors: Zhong Yi
Published: December 2021

This work extends the high-order Melnikov method established by FJ Chen and QD Wang to heteroclinic orbits, and it is used to prove, under a certain class of perturbations, the heteroclinic orbit in a planar vector field that remains unbroken. Perturbations which have this property together form the heteroclinic persisting space. The Van der Pol system is analysed as an application.
Estimation for Weibull Parameters with Generalized Progressive Hybrid Censored Data
Authors: Zuo Xuanjia , Wang Liang , Lin Huizhong , Dey Sanku , Yan Li
Published: December 2021

In this paper, the interest is in estimating the Weibull products when the available data is obtained via generalized progressive hybrid censoring. The testing scheme conducts products of interest under a more flexible way and allows collecting failure data in efficient and adaptable experimental scenarios than traditional lifetime testing. When the latent lifetime of products follows Weibull distribution, classical and Bayesian inferences are considered for unknown parameters. The existence and uniqueness of maximum likelihood estimates are established, and approximate confidence intervals are also constructed via asymptotic theory. Bayes point estimates as well as the credible intervals of the parameters are obtained, and correspondingly, Monte Carlo sampling technique is also provided for complex posterior computation. Extensive numerical analysis is carried out, and the results show that the generalized progressive hybrid censoring is an adaptive procedure in practical lifetime experiment, both proposed classical and Bayesian inferential approaches perform satisfactorily, and the Bayesian results are superior to conventional likelihood estimates.
TOPSIS Hybrid Multiattribute Group Decision-Making Based on Interval Pythagorean Fuzzy Numbers
Authors: Jun H. U. , Junmin W. U. , Jie W. U.
Published: December 2021

Aiming at the mixed multiattribute group decision-making problem of interval Pythagorean fuzzy numbers, a weighted average (WA) operator model based on interval Pythagorean fuzzy sets is constructed. Furthermore, a decision-making method based on the technique for order preference by similarity to ideal solution (TOPSIS) method with interval Pythagorean fuzzy numbers is proposed. First, based on the completely unknown weights of decision-makers and attributes, interval Pythagorean fuzzy numbers are applied to TOPSIS group decision-making. Second, the interval Pythagorean fuzzy number WA operator is used to synthesize the evaluation matrices of multiple decision-makers into a comprehensive evaluation matrix, and the relative closeness of each scheme is calculated based on the TOPSIS decision-making method. Finally, an example is given to illustrate the rationality and effectiveness of the proposed method.
Comparative Analysis for Prediction of Kidney Disease Using Intelligent Machine Learning Methods
Authors: Ifraz Gazi Mohammed , Rashid Muhammad Hasnath , Tazin Tahia , Bourouis Sami , Khan Mohammad Monirujjaman
Published: December 2021

Chronic kidney disease (CKD) is a major burden on the healthcare system because of its increasing prevalence, high risk of progression to end-stage renal disease, and poor morbidity and mortality prognosis. It is rapidly becoming a global health crisis. Unhealthy dietary habits and insufficient water consumption are significant contributors to this disease. Without kidneys, a person can only live for 18 days on average, requiring kidney transplantation and dialysis. It is critical to have reliable techniques at predicting CKD in its early stages. Machine learning (ML) techniques are excellent in predicting CKD. The current study offers a methodology for predicting CKD status using clinical data, which incorporates data preprocessing, a technique for managing missing values, data aggregation, and feature extraction. A number of physiological variables, as well as ML techniques such as logistic regression (LR), decision tree (DT) classification, and

K

-nearest neighbor (KNN), were used in this work to train three distinct models for reliable prediction. The LR classification method was found to be the most accurate in this role, with an accuracy of about 97 percent in this study. The dataset that was used in the creation of the technique was the CKD dataset, which was made available to the public. Compared to prior research, the accuracy rate of the models employed in this study is considerably greater, implying that they are more trustworthy than the models used in previous studies as well. A large number of model comparisons have shown their resilience, and the scheme may be inferred from the study’s results.
Early Prediction of Disease Progression in Patients with Severe COVID-19 Using C-Reactive Protein to Albumin Ratio
Authors: Li Yi , Li Haitao , Song Chao , Lu Rongli , Zhao Yuhao , Lin Fengyu , Han Duoduo , Chen Lingli , Pan Pinhua , Dai Minhui
Published: December 2021

Background. Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients. Methods. We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 (

n
=
465

) were divided into stable (

n
=
409

) and progressive (

n
=
56

) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission. Results. The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration (

log
−
rank
 
p
<
0.001

). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay. Conclusion. The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19.
Mechanical Characteristics of Steel Shear Keyed Joints in the Construction and Finished States
Authors: Zou Yu , Xu Dong
Published: December 2021

Joints that represent locations of discontinuity were the prominent factors affecting the overall behavior of precast segmental bridges. In this study, the steel shear key was designed, which was used to transmit the shear stress of the joints. To study the mechanical characteristics of the steel shear keyed joints in the construction and finished states, direct shear experiments and numerical analysis were carried out. The experimental results showed that the steel shear keyed joints had a high bearing capacity and good ductility. Under the action of confining stress, the joints relied on the mechanical occlusion between the steel keys to transmit the shear forces. When the load‐displacement curve entered the horizontal stage, it can still bore large relative deformation, and the bearing capacity did not decrease. In the construction state, the inelastic deformation of the steel shear key should be used to control the design value of the temporary load. In the finished state, the bearing capacity of joints should be controlled by the direct shear strength of the steel shear key, which can be calculated according to the shear formula. The shear strength of the material and size of the steel shear key are the main factors affecting the bearing capacity of steel shear keyed joints.
Research Progress on Corrosion of Equipment and Materials in Deep‐Sea Environment
Authors: Chen Sheng , Qiu Liping , Sun Shaofang , Yang Junyi , Meng Qinghua , Yang Weibo
Published: December 2021

The deep sea is the frontier of materials research in the 21st century. Owing to the particularity of pressure (15–120 MPa), hydrothermal temperature (90–400°C), and explosive fluid (strong H2S) in the deep‐sea hydrothermal field environment, the research on the corrosion mechanism of service materials in this environment under the coupling action of many harsh factors is almost blank. It has become the bottleneck of equipment and material research and development for China to explore the deep sea. This paper reviews the research progress of corrosion mechanisms of deep‐sea environmental materials at home and abroad, and forecasts the research trend and difficulties in this field, especially in the deep‐sea hydrothermal field. At the same time, it points out the urgency of the construction of harsh environment materials platform and its relevance to the discipline construction of marine college.
Simulation Study on the Evolutionary Game Mechanism of Collaborative Innovation in Supply Chain Enterprises and Its Influencing Elements
Authors: Xie Jue-Ping , Lei Huai-Ying
Published: December 2021

Collaborative innovation between companies is critical for increasing supply chain value. However, as a dynamic game process, the collaboration between manufacturer, provider, and seller in the supply chain is influenced by a range of elements. This paper is set out to investigate the collaborative innovation strategy adopted by manufacturer, supplier, and distributor (the “three players”). To meet this end, an analytical framework was built to study the evolutionary game of collaborative innovation in supply chain enterprises. Based on the analysis, this research further studied the dynamic evolutionary mechanism and influencing elements through four different simulation cases. The research showed the following. (1) When the three players have equal innovative capability, they are more willing to contribute to innovation if the projected revenue is higher reflecting an increasing coefficient of collaborative innovation gains. As a result, the three players are more likely to agree on their cooperation approach. (2) When the three players have different independent and innovative capabilities, they are more willing to innovate if the collaborative innovation gain coefficient increases, but supply chain players with stronger capability are more active to innovate than their peers. In other words, strong innovators attach particular attention to innovation. (3) When any collaborative innovation could generate profits for all players in the supply chain, the player who enjoys the benefit but lacks innovative capability will be unwilling to cooperate with others if additional gains rise. Thus, better maintenance of the stability of the collaborative innovation system requires a strictly implemented coordination mechanism.
Effect of Lanthanum Cerium Cysteine on Cure Characteristics, Mechanical Properties, and Thermooxidative Aging for Natural Rubber
Authors: Zhang Wentao , Liu Zhaogang , Li Shuai , Hao Wei , Hu Yanhong , Wu Jinxiu
Published: December 2021

In this work, a novel additive lanthanum cerium cysteine (LC-Cys), with the molecular formula La0.35Ce0.65(Cys)3Cl3·3H2O, was successfully synthesized through complex decomposition reaction of L-Cysteine and chlorinated rare earths. The effects of additive LC-Cys on cure characteristics, mechanical properties, and thermooxidative aging were investigated. LC-Cys as a multifunctional additive was applied to increase the curing rate and reduce the content of zinc oxide in the presence of the sulfur vulcanization system. It was found that the vulcanizates filled with (5ZnO/2LC-Cys) exhibited the highest modulus, which indirectly indicated the high crosslink and stiffness of the vulcanizates. Moreover, the vulcanizates with LC-Cys showed excellent mechanical properties and resistance to thermooxidative aging. Compared to NR composites filled with normal ZnO, LC-Cys even enhanced the mechanical strength and thermooxidative aging properties with 40% lower ZnO addition.
Training Needs in Light of the Degree of Awareness of Modern Teaching Strategies and Their Application in the Tertiary Level during the COVID-19 Pandemic
Authors: Alamro AbdulAziz R.
Published: December 2021

This study aimed to evaluate modern teaching methods applied by the staff at the University of Hail during the COVID-19 pandemic to identify the most important causes, needs, and barriers from their perspective. Also, the study aimed to reveal individual differences (gender, academic rank, or experience) of statistical significance in the staff’s degree of use. To achieve the objectives of the study, the researcher used descriptive analysis on a sample of 164 faculty members. The researcher designed a five-axis questionnaire. The results indicated the importance of e-training when using modern teaching methods. Also, it was clear that the research sample uses MTM to some extent, and the use of modern teaching strategies was found to be moderate. Gender, academic rank, years of experience in the field of university education, and academic specialization did not affect training needs. In addition, the results showed that the most important reason for using MTM during the COVID-19 pandemic was “Mastery of how to use it.”
First‐Principles Calculations to Investigate the Third‐Order Elastic Constants and Mechanical Properties of Mg, Be, Ti, Zn, Zr, and Cd
Authors: Yang Xiaoqing , Meng Zhenya , Cao Hailin
Published: December 2021

We present theoretical studies for the third‐order elastic constants of Mg, Be, Ti, Zn, Zr, and Cd with a hexagonal‐close‐packed (HCP) structure. The method of homogeneous deformation combined with first‐principles total‐energy calculations is employed. The deformation gradient Fij is applied to the crystal lattice vectors ri, and the elastic strain energy can be obtained from the first‐principles calculation. The second‐ and third‐order elastic constants are extracted by a polynomial fit to the calculated energy‐strain results. In order to assure the accuracy of our method, we calculated the complete set of the equilibrium lattice parameters and second‐order elastic constants for Mg, Be, Ti, Zn, Zr, and Cd, and our results provide better agreement with the previous calculated and experimental values. Besides, we have calculated the pressure derivatives of SOECs related to third‐order elastic constants, and high‐pressure effects on elastic anisotropy, ductile‐to‐brittle criterion, and Vickers hardness are also investigated. The results show that the hardness model is more appropriate than for HCP metals under high pressure.
Study on College English Online Teaching Model in Mixed Context Based on Genetic Algorithm and Neural Network Algorithm
Authors: Ma Xiaoxia
Published: December 2021

College English classroom teaching evaluation is an important basis for understanding teaching level and improving teaching quality. The traditional college English classroom teaching evaluation is mainly carried out through questionnaires and scales, but this method is time-consuming and laborious, inevitably introduces subjective errors, and reduces the accuracy and credibility of the evaluation results. In recent years, the rise and development of wisdom education not only provides a more convenient and efficient modern education form but also brings new ideas for classroom teaching evaluation. A subjective and objective fusion statistical evaluation model based on multidirectional genetic variation method and optimized neural network is proposed. The algorithm avoids subjective errors and improves the accuracy and reliability of the evaluation results, and a comprehensive evaluation model is constructed. Finally, according to different evaluation indexes, a systematic visualization scheme is designed to generate students’ classroom learning evaluation report and teachers' classroom teaching evaluation report, respectively, and visualize them on the web.
A Graph Optimization-Based Acoustic SLAM Edge Computing System Offering Centimeter-Level Mapping Services with Reflector Recognition Capability
Authors: Zhou Zou , Zhang Guoli , Zheng Fei , Wang Tuyang , Chen Longjie , Duan Nan
Published: December 2021

Robots can use echo signals for simultaneous localization and mapping (SLAM) services in unknown environments where its own camera is not available. In current acoustic SLAM solutions, the time of arrival (TOA) in the room impulse response (RIR) needs to be associated with the corresponding reflected wall, which leads to an echo labelling problem (ELP). The position of the wall can be derived from the TOA associated with the wall, but most of the current solutions ignore the effect of the cumulative error in the robot’s moving state measurement on the wall position estimation. In addition, the estimated room map contains only the shape information of the room and lacks position information such as the positions of doors and windows. To address the above problems, this paper proposes a graph optimization-based acoustic SLAM edge computing system offering centimeter-level mapping services with reflector recognition capability. In this paper, a robot equipped with a sound source and a four-channel microphone array travels around the room, and it can collect the room impulse response at different positions of the room and extract the RIR cepstrum feature from the room impulse response. The ELP is solved by using the RIR cepstrum to identify reflectors with different absorption coefficients. Then, the similarity of the RIR cepstrum vectors is used for closed-loop detection. Finally, this paper proposes a method to eliminate the cumulative error of robot movement by fusing IMU data and acoustic echo data using graph-optimized edge computation. The experiments show that the acoustic SLAM system in this paper can accurately estimate the trajectory of the robot and the position of doors, windows, and so on in the room map. The average self-localization error of the robot is 2.84 cm, and the mapping error is 4.86 cm, which meet the requirement of centimeter-level map service.
Solving an Integral Equation by Using Fixed Point Approach in Fuzzy Bipolar Metric Spaces
Authors: Mani Gunaseelan , Gnanaprakasam Arul Joseph , Haq Absar Ul , Jarad Fahd , Baloch Imran Abbas
Published: December 2021

The purpose of this manuscript is to obtain some fixed point results under mild contractive conditions in fuzzy bipolar metric spaces. Our results generalize and extend many of the previous findings in the same approach. Moreover, two examples to support our theorems are obtained. Finally, to examine and strengthen the theoretical results, the existence and uniqueness of the solution to a nonlinear integral equation was studied as a kind of applications.
Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Systematic Review and Meta‐Analysis
Authors: Zhang Jialing , Lu Xiangxue , Feng Jianan , Li Han , Wang Shixiang
Published: December 2021

Introduction. The present meta‐analysis was to explore the efficacy of hydroxychloroquine (HCQ) in IgA nephropathy patients in terms of proteinuria. Method. We systematically searched PubMed and Embase for studies that compared HCQ and other treatments to reduce proteinuria in patients with IgA nephropathy up to June 2021. Mean ± SD of percentage change and level of proteinuria was calculated. Results. A total of 5 studies with 587 participants were included. IgA nephropathy patients who received HCQ were at a lower level of mean proteinuria at 6 months. However, there was no statistical difference between HCQ and control group considering percentage reduction in proteinuria. The long‐term therapeutic effect of HCQ might be inferior to HCQ and renin‐angiotensin‐aldosterone system inhibition. Conclusion. HCQ might play a role in the reduction of proteinuria in IgA nephropathy patients. The addition of HCQ to other immunosuppressive agents should be clarified further.
Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics
Authors: Shi Chang Yi , Yu Chen Huan , Yu Wen Ying , Ying Hua Zhong
Published: December 2021

The microbiota colonized in the human body has a symbiotic relationship with human body and forms a different microecosystem, which affects human immunity, metabolism, endocrine, and other physiological processes. The imbalance of microbiota is usually linked to the aberrant immune responses and inflammation, which eventually promotes the occurrence and development of respiratory diseases. Patients with chronic respiratory diseases, including asthma, COPD, bronchiectasis, and idiopathic pulmonary fibrosis, often have alteration of the composition and function of intestinal and lung microbiota. Gut microbiota affects respiratory immunity and barrier function through the lung-gut microbiota, resulting in altered prognosis of chronic respiratory diseases. In turn, lung dysbiosis promotes aggravation of lung diseases and causes intestinal dysfunction through persistent activation of lymphoid cells in the body. Recent advances in next-generation sequencing technology have disclosed the pivotal roles of lung-gut microbiota in the pathogenesis of chronic respiratory diseases. This review focuses on the association between the gut-lung dysbiosis and respiratory diseases pathogenesis. In addition, potential therapeutic modalities, such as probiotics and fecal microbiota transplantation, are also evaluated for the prevention of chronic respiratory diseases.
Pyroptosis-Related Gene Signature Is a Novel Prognostic Biomarker for Sarcoma Patients
Authors: Wei Dalong , Lan Xiaoling , Huang Zhiqun , Tang Qiang , Wang Zechen , Ma Yanfei , Wei Liuzhi , Wei Qiuju , Zhao Jingjie , Shen Jiajia , He Siyuan , Song Jian , Meng Lingzhang , Tang Qianli
Published: December 2021

Sarcoma is a rare and an extremely aggressive form of cancer that originates from mesenchymal cells. Pyroptosis exerts a dual effect on tumours by inhibiting tumour cell proliferation while creating a microenvironment suitable for tumour cell development and proliferation. However, the significance of pyroptosis-related gene (PRG) expression in sarcoma has not yet been evaluated. Here, we conduct a retrospective analysis to examine PRG expression in 256 sarcoma samples from The Cancer Genome Atlas database. We identified the PRGs that had a significant correlation with overall patient survival in sarcoma by performing a univariate Cox regression analysis. Subsequently, we conducted a LASSO regression analysis and created a risk model for a six-PRG signature. As indicated from the Kaplan–Meier analysis, this signature revealed a significant difference between high- and low-risk sarcoma patients. A receiver operating characteristic curve analysis confirmed that this signature could predict overall patient survival in sarcoma patients with high sensitivity and specificity. Gene ontology annotation and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses revealed that five independent PRGs were closely associated with increased immune activity. Moreover, we also deciphered that increased number of immune cells infiltrated the tumour microenvironment in sarcoma. In brief, the PRG signature can effectively act as novel prognostic biomarker for sarcoma patients and is associated with the tumour immune microenvironment.
Covid 19 y Restricciones Sanitarias
Authors: Ponce Carlos
Published: December 2021

Hasta la reciente aparición de las vacunas, la imposición de cuarentenas fue la respuesta sanitaria más utilizada por la mayoría de los países para enfrentar la pandemia de Covid-19. El objetivo de estas medidas fue minimizar la cantidad de contagios y muertes. En la mayoría de los países las restricciones sanitarias fueron, al menos, parcialmente exitosas. En un reciente artículo, Pincombe et. al (2021) estudia este asunto en detalle. Los autores analizan los efectos de las cuarentenas sobre los casos de covid y tasas de mortalidad para 113 países. Sus resultados sugieren que el éxito de estas medidas estuvo positivamente correlacionado con el nivel de ingreso del país. Continuar leyendo...
Abstract P125: Combined inhibition of SHP2 and CDK4/6 is active in NF1-associated malignant peripheral nerve sheath tumor
Authors: Wang Jiawan , Calizo Ana , Pollard Kai , Hirbe Angela C. , Pratilas Christine A.
Published: December 2021

Background: NF1 is an essential negative regulator of RAS activity and is altered in nearly 90% of malignant peripheral nerve sheath tumors (MPNST). Additional recurrent molecular changes include loss of function alterations in CDKN2A, TP53, EED and SUZ12, but molecular targeting of these genomic events represents a unique challenge. We previously reported that the efficacy of MEK inhibitor is limited by adaptive activation of receptor tyrosine kinases and the adaptor protein SHP2, and that combined inhibition of MEK and SHP2 is effective in MPNST. Loss of CDKN2A, inactivation of RB1, and hyperactivation of cyclin dependent kinases (CDK) in MPNST also suggest that small-molecule CDK4/6 inhibitors (CDK4/6i) may be a potential therapeutic strategy, but monotherapy with CDK4/6i also demonstrates limited activity. Given the dependency of D-cyclins on RAS signaling, we hypothesize that the anti-tumor effects of CDK4/6i may be potentiated by agents (SHP2i) targeting the upstream activators of RAS. Methods: The effects of shRNA-mediated inducible SHP2 knockdown on RAS signaling, short-term and long-term cell growth, and response to CDK4/6i were examined using immunoblotting, high throughput proliferation assays, and colony formation assays. Combined effects of SHP2i plus CDK4/6i on signaling, cell and tumor growth were assessed. Pharmacodynamic (PD) assays were performed on tumors extracted following drug treatment in patient-derived xenograft (PDX) models. Results: Despite a modest effect of SHP2 knockdown on ERK signaling, shSHP2 reduced MPNST cell growth. SHP2 knockdown or SHP2i treatment alleviated activation of ERK signaling and cyclin D1 expression induced by CDK4/6i, and enhanced the sensitivity to CDK4/6i. Combination benefit was observed in in vitro cell growth and in vivo PDX. Although some PDX models demonstrated similar responses to SHP2i alone or SHP2i + CDK4/6i during the initial 4 weeks on treatment, we found more sustained growth inhibition exerted by the combination. PD studies demonstrated a decrease in p-ERK levels in tumors treated with either SHP2i alone or the SHP2i/CDK4/6i combination. Conclusions: Our preliminary data demonstrate that the combined inhibition of SHP2 and CDK4/6 is active and produces durable response in models of NF1-associated MPNST. This combination strategy may represent a novel treatment strategy for patients with MPNST.

Citation Format: Jiawan Wang, Ana Calizo, Kai Pollard, Angela C. Hirbe, Christine A. Pratilas. Combined inhibition of SHP2 and CDK4/6 is active in NF1-associated malignant peripheral nerve sheath tumor [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P125.
Management of Lambdoid Craniosynostosis: A Comprehensive and Systematic Review
Authors: Reardon Taylor , Fiani Brian , Kosarchuk Jacob , Parisi Anthony , Shlobin Nathan A.
Published: December 2021

Background: Craniosynostosis is a condition characterized by the premature fusion of 2 or more skull bones. Craniosynostosis of the lambdoid suture is one of the rarest forms, accounting for 1–4% of all craniosynostoses. Documented cases are separated into simple (single suture), complex (bilateral), and associated with adjacent synostoses (“Mercedes Benz” Pattern) or syndromes (i.e., Crouzon, Sathre-Chotzen, Antley-Bixler). This condition can manifest phenotypic deformities and neurological sequelae that can lead to impaired cognitive function if improperly treated or left undiagnosed. Preferred surgical techniques have varied over time but all maintain the common goals of establishing proper head shape and preventing of complications that could contribute to aforementioned sequelae. Summary: This comprehensive review highlights demographic distributions, embryological development, pathogenesis, clinical presentation, neurological sequelae, radiologic findings, surgical techniques, surgical outcomes, and postoperative considerations of patients with lambdoid craniosynostosis presentation. In addition, a systematic review was conducted to explore the operative management of lambdoid craniosynostosis using PubMed, Embase, and Scopus databases, with 38 articles included after screening. Key Messages: Due to a low volume of published cases, diagnosis and treatment can vary. Large overlap in presentation can occur in patients that display lambdoid craniosynostosis and posterior plagiocephaly, furthering the need for comprehensive analysis. Possessing the knowledge and tools to properly assess patients with lambdoid craniosynostosis will allow for more precise care and improved outcomes.
End-of-Life: Patientinnen und Patienten rechtzeitig einbinden
Authors: Zimmermann Tanja
Published: December 2021

Background: Decisions to limit treatment (DLTs) are important to protect patients from overtreatment but constitute one of the most ethically challenging situations in oncology practice. In the Ethics Policy for Advance Care Planning and Limiting Treatment study (EPAL), we examined how often DLT preceded a patient’s death and how early they were determined before (T1) and after (T2) the implementation of an intrainstitutional ethics policy on DLT. Methods: This prospective quantitative study recruited 1.134 patients with haematological/oncological neoplasia in a period of 2×6 months at the University Hospital of Munich, Germany. Information on admissions, discharges, diagnosis, age, DLT, date and place of death, and time span between the initial determination of a DLT and the death of a patient was recorded using a standardised form. Results: Overall, for 21% (n = 236) of the 1.134 patients, a DLT was made. After implementation of the policy, the proportion decreased (26% T1/16% T2). However, the decisions were more comprehensive, including more often the combination of ‹Do not resuscitate› and ‹no intense care unit› (44% T1/64% T2). The median time between the determination of a DLT and the patient’s death was similarly short with 6 days at a regular ward (each T1/T2) and 10.5/9 (T1/T2) days at a palliative care unit. For patients with solid tumours, the DLTs were made earlier at both regular and palliative care units than for the deceased with haematological neoplasia. Conclusion: Our results show that an ethics policy on DLT could sensitise for treatment limitations in terms of frequency and extension but had no significant impact on timing of DLT. Since patients with haematological malignancies tend to undergo intensive therapy more often during their last days than patients with solid tumours, special attention needs to be paid to this group. To support timely discussions, we recommend the concept of advance care planning.
Low-Titer Group O Whole-Blood Resuscitation in the Prehospital Setting in Israel: Review of the First 2.5 Years’ Experience
Authors: Levin Dan , Zur Maoz , Shinar Eilat , Moshe Tzadok , Tsur Avishai M. , Nadler Roy , Yazer Mark H. , Epstein Danny , Avital Guy , Gelikas Shaul , Glassberg Elon , Benov Avi , Chen Jacob
Published: December 2021

Introduction: The Israeli Defense Forces Medical Corps (IDF-MC) implemented the use of low-titer group O whole blood (LTOWB) as the first-choice resuscitation fluid in the IDF airborne Combat Search and Rescue Unit (IDF-CSAR) for aerial evacuation of both military and civilian casualties in June 2018 for injured patients with hemorrhagic shock and at least one of the following: systolic blood pressure <90 mm Hg, heart rate >130 beats/min, deterioration of consciousness without head injury or hemoglobin concentration ≤7 g/dL. Method: All casualties treated with LTOWB by IDF-CSAR providers from June 2018 to January 2021 were included. Demographic and prehospital treatment data were collected in order to check compliance and adherence to the IDF-MC guidelines. This is a follow-up retrospective report. Results: Overall, 1,608 LTOWB units were supplied to the IDF-CSAR during the study period. Of these, 33 were transfused to 27 casualties; 17 (69%) with blunt injury, 8 (29.6%) with penetrating injuries, and 1 (3.7%) with gastrointestinal bleeding without trauma. The leading cause of injury was motor vehicle accidents. A total of 23 casualties received 1 unit of LTOWB, 3 received 2 units and 1 patient received 4 units. Two casualties were children. The median heart rate was 120 beats/min, 8 (29.6%) casualties had heart rates >130 beats/min. Median systolic blood pressure was 95 mm Hg, 7 (26%) casualties had blood pressure <90 mm Hg. The median Glasgow Coma Score was 14. No adverse reactions were documented following the administration of LTOWB. 77.8% of patients received LTOWB in adherence to the guidelines. Conclusion: Appropriate administration of LTOWB has improved over time in IDF-CSAR. Using LTOWB is feasible and simpler than administering packed red blood cells and plasma concurrently. Further efforts are needed to introduce LTOWB in other prehospital and in-hospital scenarios, with an increase in the maximum antibody titer threshold, to meet the expected increase in demand.
Prevention of Intra-Abdominal Adhesions Using the Combination of Mediclore® and a Statin
Authors: Park Jesung , Kang Hyun , Choi Yoo Shin , Suh Suk-Won , Hong Soon Auck , Choi Geun Joo , Sim Woo Jung
Published: December 2021

Purpose: This study investigated the antiadhesive effects of Mediclore®, rosuvastatin, and a combination of Mediclore and rosuvastatin in a rat adhesion model. Methods: The adhesion models (a total of 58 adult male rats) were divided into 4 groups. The control group (group C) received no special materials except for a saline. The experimental groups were treated with 5 mL of Mediclore (group M), rosuvastatin (group R), or rosuvastatin and Mediclore (group RM), and these materials were intraperitoneally placed under the incision. At postoperative day 14, the rats underwent re-laparotomy and adhesiolysis. Three investigators blinded to group assignment scored the extent of adhesion formation, the numbers of remote adhesions, and the extent of acute/chronic inflammation, fibrosis, edema, and congestion on resected specimens via histologic examination. Results: The macroscopic adhesion score in group RM (7.27 ± 3.51) was significantly lower than those in groups C (13.36 ± 2.24) and R (11.71 ± 1.98); group M (9.13 ± 4.09) had a significantly lower adhesion score than group C. The number of remote adhesions was significantly lower in groups R and RM than in group C. The acute inflammation score, chronic inflammation score, and fibrosis score in group RM; the acute inflammation score in group R; and the fibrosis score in group M were significantly lower than those in group C. Conclusion: The intraperitoneal application of Mediclore and a combination of Mediclore and rosuvastatin effectively reduced postoperative adhesions.
Multicenter Validation of Individual Preoperative Motor Outcome Prediction for Deep Brain Stimulation in Parkinson’s Disease
Authors: Habets Jeroen G.V. , Herff Christian , Fasano Alfonso A. , Beudel Martijn , Kocabicak Ersoy , Schnitzler Alfons , Snineh Muneer Abu , Kalia Suneil K. , Ramirez-Gómez Carolina , Hodaie Mojgan , Munhoz Renato P. , Rouleau Eline , Yildiz Onur , Linetsky Eduard , Schuurman Rick , Hartmann Christian J. , Lozano Andres M. , De Bie Rob M.A. , Temel Yasin , Janssen Marcus L.F.
Published: December 2021

Background: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for Parkinson’s disease (PD) patients suffering from motor response fluctuations despite optimal medical treatment, or severe dopaminergic side effects. Despite careful clinical selection and surgical procedures, some patients do not benefit from STN DBS. Preoperative prediction models are suggested to better predict individual motor response after STN DBS. We validate a preregistered model, DBS-PREDICT, in an external multicenter validation cohort. Methods: DBS-PREDICT considered eleven, solely preoperative, clinical characteristics and applied a logistic regression to differentiate between weak and strong motor responders. Weak motor response was defined as no clinically relevant improvement on the Unified Parkinson’s Disease Rating Scale (UPDRS) II, III, or IV, 1 year after surgery, defined as, respectively, 3, 5, and 3 points or more. Lower UPDRS III and IV scores and higher age at disease onset contributed most to weak response predictions. Individual predictions were compared with actual clinical outcomes. Results: 322 PD patients treated with STN DBS from 6 different centers were included. DBS-PREDICT differentiated between weak and strong motor responders with an area under the receiver operator curve of 0.76 and an accuracy up to 77%. Conclusion: Proving generalizability and feasibility of preoperative STN DBS outcome prediction in an external multicenter cohort is an important step in creating clinical impact in DBS with data-driven tools. Future prospective studies are required to overcome several inherent practical and statistical limitations of including clinical decision support systems in DBS care.
Impact of Ventilation Modes on Bronchoscopic Chartis Assessment Outcome in Candidates for Endobronchial Valve Treatment
Authors: Saccomanno Jacopo , Ruwwe-Glösenkamp Christoph , Neumann Konrad , Doellinger Felix , Lenga Pavlina , Pappe Eva , Suttorp Norbert , Witzenrath Martin , Hübner Ralf-Harto
Published: December 2021

Background: Endobronchial valve therapy has proven to reduce lung hyperinflation and decrease disease burden in patients with severe lung emphysema. Exclusion of collateral ventilation (CV) of the targeted lobe by using an endobronchial assessment system (Chartis; PulmonX, Drive Redwood City, CA, USA) in combination with software-based fissure integrity analysis (FCS [fissure completeness score]) of computed tomography scans of the lung are established tools to select appropriate patients for endobronchial valve treatment. So far, there is no conclusive evidence if the ventilation mode during bronchoscopy impacts the outcome of Chartis assessments. Methods: Patients with Chartis assessments and software-based quantification of FCS (StratX; PulmonX, Drive Redwood City, CA, USA) were enrolled in this retrospective study. During bronchoscopy, pulmonary fissure integrity was evaluated with the Chartis assessment system in each patient first under spontaneous breathing and subsequently under high-frequency (HF) jet ventilation. Results: In total, 102 patients were analyzed. Four Chartis phenotypes CV positive (CV+), CV negative (CV−), low flow, and low plateau in spontaneous breathing and HF jet ventilation were identified. The frequency of each Chartis phenotype per lobe was similar in both settings. When comparing Chartis assessments in spontaneous breathing and HF jet ventilation, there was an overall good concordance rate for all analyzed fissures. In agreement, receiver operating characteristic analysis of the FCS showed an almost similar prediction for CV+ and CV− status independent of the ventilation modes. Conclusion: Chartis assessment in spontaneous breathing and HF jet ventilation had similar rates in detecting CV in lung emphysema. Our results suggest that both modes are equivalent for the assessment of CV.
Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids
Authors: Cinege Gyöngyi , Magyar Lilla B. , Kovács Attila L. , Lerner Zita , Juhász Gábor , Lukacsovich David , Winterer Jochen , Lukacsovich Tamás , Hegedűs Zoltán , Kurucz Éva , Hultmark Dan , Földy Csaba , Andó István
Published: December 2021

Multinucleated giant hemocytes (MGHs) represent a novel type of blood cell in insects that participate in a highly efficient immune response against parasitoid wasps involving isolation and killing of the parasite. Previously, we showed that circulating MGHs have high motility and the interaction with the parasitoid rapidly triggers encapsulation. However, structural and molecular mechanisms behind these processes remained elusive. Here, we used detailed ultrastructural analysis and live cell imaging of MGHs to study encapsulation in Drosophila ananassae after parasitoid wasp infection. We found dynamic structural changes, mainly driven by the formation of diverse vesicular systems and newly developed complex intracytoplasmic membrane structures, and abundant generation of giant cell exosomes in MGHs. In addition, we used RNA sequencing to study the transcriptomic profile of MGHs and activated plasmatocytes 72 h after infection, as well as the uninduced blood cells. This revealed that differentiation of MGHs was accompanied by broad changes in gene expression. Consistent with the observed structural changes, transcripts related to vesicular function, cytoskeletal organization, and adhesion were enriched in MGHs. In addition, several orphan genes encoding for hemolysin-like proteins, pore-forming toxins of prokaryotic origin, were expressed at high level, which may be important for parasitoid elimination. Our results reveal coordinated molecular and structural changes in the course of MGH differentiation and parasitoid encapsulation, providing a mechanistic model for a powerful innate immune response.
Induced Polyspecificity of Human Secretory Immunoglobulin A Antibodies: Is It Possible to Improve Their Ability to Bind Pathogens?
Authors: Gorshkova Ekaterina N. , Pashova Shina , Vasilenko Ekaterina A. , Tchurina Tatiana S. , Razzorenova Elizaveta A. , Starkina Olga V. , Dimitrova Petya , Pashov Anastas , Vassilev Tchavdar Lubenov
Published: December 2021

Introduction: As has been shown previously, various protein-modifying agents can change the antigen-binding properties of immunoglobulins. However, induced polyspecificity of human secretory immunoglobulin A (sIgA) has not been previously characterized in detail. Methods: In the present study, human secretory immunoglobulin A (IgA) was exposed to buffers with acidic pH, to free heme, or to pro-oxidative ferrous ions, and the antigen-binding behavior of the native and modified IgA to viral and bacterial antigens was compared using Western blotting and enzyme-linked immunosorbent assay. The ability of these agents to modulate the antigen-binding properties of human sIgA toward a wide range of pathogen peptides was investigated using an epitope microarray. Results: We have shown that acidic pH, heme, and pro-oxidative ferrous ions influenced the binding of secretory IgA in opposite directions (either increasing or decreasing); however, the strongest effect was observed when using buffers with low pH. This fraction had the highest number of affected reactivities; most of them were increased and most of the new ones were toward common pathogens. Conclusions: Thus, it was shown that all investigated treatments can alter to some degree the antigen-binding of secretory IgA, but acidic pH has the most potentially beneficial effect by increasing binding to a largest number of common pathogens’ antigens.