bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Environmental Fluctuations on Stock Markets: Empirical Evidence from South Asia
Authors: Zahid R. M. Ammar , Khurshid Muzammil , Waheed Minha , Sanni Tajudeen
Published: July 2022

The proportionate use of energy represents economic activity as well as environmental degradation. This study intends to examine the volatility spillover of environmental fluctuations (energy prices) to the stock markets of south Asian countries (i.e., Bangladesh, India, and Pakistan). In this regard, the data have been gathered from the Thomson Reuters DataStream from 2013 to 2021. This study has applied the Granger causality test and ARCH‐GARCH (1, 1). It concludes that the bidirectional causality exists between the environmental prices (i.e., energy market) and Bangladesh, Pakistan, and India stock markets (BSE‐100, DSE‐30, and KSE‐100, respectively). The empirical findings of this study show that there are volatility spillovers from the energy to the stock markets of Pakistan and India. On the other hand, no volatility spillover is observed from the energy to the stock market of Bangladesh. Moreover, the study implies that investors should invest in these stock markets to reduce the risk involved with diversification.
Ranking of Urban Brand Influence Based on Social Media Comment Mining
Authors: Li Yang , Lv Zongli
Published: July 2022

Social media reviews play an increasingly important role in ranking the influence of urban brands. In this study, the public social media review database is mined, and a regression model of urban influence is established. Firstly, this study introduces text mining and data collection. Comment data are collected from static websites and dynamic websites, and ICTCLAS word segmentation tool is used to preprocess the comment data. The algorithm of urban influence level is established, and finally the regression model of urban brand influence is established. A database of 10000 city-related reviews was used in the experiment. The gender thesaurus is established to further improve the accuracy of the experimental results. The feasibility of the model is verified from two aspects: expectation calculation and standardization. This paper analyzes the composition of citizens who comment on social media and the proportion of comment content and puts forward some suggestions to enhance the influence of the city. Finally, it summarizes the popular comments in different months in December and obtains the force points to enhance the influence of the city in different time periods from the structure.
Antitheft Technology for Smart Carts Using Dual Beacons and a Weight Sensor
Authors: Chung Myoungbeom
Published: July 2022

Recently, various forms of theft and loss prevention technologies have been proposed, including beacons for the prevention of missing children, the theft of strollers, and the loss of passports. However, technologies using only one beacon may send a notification that they have been lost even when they are not outside the range of the beacon signal. In addition, this technology often fails to prevent loss because it only sends an alarm to smart devices after they are a long distance from the owner. Therefore, we propose a technology that uses two beacons to improve antitheft performance. At the same time, we propose an antitheft technology for smart carts using dual beacons and a weight sensor. To verify the performance of the proposed method, we performed a comparative experiment with an existing method using one beacon, and the experimental results showed that the proposed method had 96.5% accuracy. In addition, the antitheft technology using a weight sensor also confirmed that the theft notification was highly accurate. Thus, the proposed technology will be useful for protecting the luggage of those who use airport smart carts and will also be useful for a variety of other purposes, including the prevention of missing children, the theft of strollers, and the loss of passports.
Analysis of Risk Factors of Coagulation Dysfunction and Hemorrhage in Newly Diagnosed Hyperleukocytic Acute Myeloma Leukemia
Authors: Xu Anjie , Liu Pan , Zhou Fuling
Published: July 2022

Purpose. To explore whether and why abnormal coagulation function and hemorrhage can appear in patients with hyperleukocytic acute myeloid leukemia (HAML). Method. We retrospectively reviewed the charts of 724 acute myeloid leukemia (AML) patients admitted with a white blood cell count of >100 × 109/L between 2010 and 2019 in order to analyze the coagulation index of patients with HAML and explore the correlation of abnormal coagulation. Result. Prothrombin time (PT) was extended in group HAML compared with group non‐HAML. Respiratory failure, intracranial hemorrhage, and infection were more common in the HAML group. Among the 76 HAML patients, there were 33 patients who had ≥3 abnormal items of coagulation index, and 51.5% of them had level 2 hemorrhage which was more than level 0 hemorrhage, and the difference is statistically significant (P < 0.01). Similarly, we can discover that 40.9% of patients with 2 abnormal items had level 2 hemorrhage in contrast to 0 abnormal items. The use of hydroxyurea had a significant effect on PT and D‐dimer (DD). Survival analysis by the Kaplan–Meier method showed that there were statistically significant differences in white blood cell (WBC) count＞200 × 109//L and DD. Abnormal PT is associated with WBC count＞200 × 109//L, and abnormal activated partial thromboplastin time (APTT) is associated with HLA‐DR mutation. Infection and respiratory failure were independent influencing factors for the coagulation of patients. Conclusion. DD had a marked effect on the survival rate. Infection and respiratory failure were independent influencing factors for the coagulation of patients.
Study on the Influencing Mechanism of Human Chorionic Gonadotropin (hCG) on Oocyte Maturation in Patients with Polycystic Ovary Syndrome
Authors: Jiang Jingjing , Gao Shanshan , Han Ting
Published: July 2022

The study was aimed at investigating the influence of human chorionic gonadotropin (hCG) hormone on oocyte maturation in the patients with polycystic ovary syndrome (PCOS). A total of 54 patients with PCOS who received in vitro maturation (IVM) treatment in the Cheeloo College of Medicine, Shandong University, were divided into two groups: one group who underwent hCG injections was the observation group (OG;

n
=
27

) and other was the control group (CG;

n
=
27

) with no hCG injection. The oocyte development and the expression of steroid hormone synthesis-related genes including gonadotropin-releasing hormone receptor (GnRHR), Conexin43, epidermal growth factor-related genes, luteinizing hormone/choriogonadotropin receptor (LHCGR), epiregulin (EREG), and vascular endothelial growth factor (VEGF) were examined. The human ovarian granulosa cell line (SVOG cells) and ovarian epithelial cell line (HOSEpiC cells) were employed to analyze the effect of hCG on the biological behaviour of cells. As a result, OG showed higher normal fertilization, cleavage, and high-qualified embryo rate than CG. Expression levels of GnRHR, Cx43, LHCGR, EREG, and VEGF were significantly elevated in granulosa cells in the OG group. Western blot revealed that phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and rapamycin (mTOR) proteins were decreased in granulosa cells under hCG intervention. A biological behaviour test indicated that the multiplication capacity of hCG-intervened SVOG and HOSEpiC was increased, while the apoptosis was decreased. In conclusion, hCG could accelerate follicular development and oocyte maturation by activating oocyte maturation genes in PCOS patients, which could significantly improve and popularize the application of IVM technology.
K-Mer Spectrum-Based Error Correction Algorithm for Next-Generation Sequencing Data
Authors: AlEisa Hussah N. , Hamad Safwat , Elhadad Ahmed
Published: July 2022

In the mid-1970s, the first-generation sequencing technique (Sanger) was created. It used Advanced BioSystems sequencing devices and Beckman’s GeXP genetic testing technology. The second-generation sequencing (2GS) technique arrived just several years after the first human genome was published in 2003. 2GS devices are very quicker than Sanger sequencing equipment, with considerably cheaper manufacturing costs and far higher throughput in the form of short reads. The third-generation sequencing (3GS) method, initially introduced in 2005, offers further reduced manufacturing costs and higher throughput. Even though sequencing technique has result generations, it is error-prone due to a large number of reads. The study of this massive amount of data will aid in the decoding of life secrets, the detection of infections, the development of improved crops, and the improvement of life quality, among other things. This is a challenging task, which is complicated not just by a large number of reads and by the occurrence of sequencing mistakes. As a result, error correction is a crucial duty in data processing; it entails identifying and correcting read errors. Various k-spectrum-based error correction algorithms’ performance can be influenced by a variety of characteristics like coverage depth, read length, and genome size, as demonstrated in this work. As a result, time and effort must be put into selecting acceptable approaches for error correction of certain NGS data.
Construction of Inflation Forecasting Model Based on Ensemble Empirical Mode Decomposition and Bayesian Model
Authors: Xia Chunlian , Huang Jing
Published: July 2022

The high explanatory power of the first-order lag term of inflation in the inflation explanatory factor is that, on the one hand, the calculation of annual inflation indicators makes the inflation values of adjacent months cover the high correlation caused by the common price increase, and on the other hand, it also shows that people’s perception of inflation is high. Some adaptability is expected. Although there are many Bayesian models available, due to the limitation of high-dimensional characteristics of the economy, most of the current inflation forecasting researches focus on a variety of generalized naive Bayesian models. By summarizing and analyzing the structural characteristics, learning methods, and classification principles of different Bayesian models, this paper finds out the important factors that affect the performance of the models and provides a theoretical basis for further improving the performance of Bayesian inflation forecasting. In this paper, the empirical mode decomposition method is introduced into inflation forecasting, and EEMD has obvious advantages in dealing with nonstationary and nonlinear time series and can decompose the signal according to the time scale characteristics of the data itself. Decompose the original time series step by step to generate eigenmode functions with different time scales. It is divided into high-frequency sequence and low-frequency sequence. Use rolling method and iterative method to construct subsamples for the sample data in this sample interval, forecast the inflation rate of each subsample interval in the next 12 months, and then compare the predicted value with the actual value to obtain a certain constructive conclusion. The predicted value is relatively close to the real value, which has theoretical and practical significance, and the predicted results obtained have no obvious regularity, but the root mean square error can be kept within 60%. By comparing the predicted value and the actual value, it can be seen that the prediction effect of the EEMD model is better.
Intrinsic ROS Drive Hair Follicle Cycle Progression by Modulating DNA Damage and Repair and Subsequently Hair Follicle Apoptosis and Macrophage Polarization
Authors: Liu Mingsheng , Liu Xiaomei , Wang Yuan , Sui Yutong , Liu Feilin , Liu Zinan , Zou Fei , Zuo Kuiyang , Wang Ziyu , Sun Wei , Xu Qi , Liu Dan , Liu Jinyu
Published: July 2022

Hair follicles (HFs) maintain homeostasis through the hair cycles; therefore, disrupting the hair cycle may lead to hair loss. Our previous study showed that apoptosis-inducing factor (AIF) nuclear translocation and poly [ADP-ribose] polymerase 1 (PARP1) upregulation induced apoptosis in mouse hair follicles during the hair cycle transition from anagen to catagen. However, the mechanism underlying this phenomenon remains unclear. In this study, we found that intrinsic ROS levels increased during the hair follicle cycle transition from anagen to catagen, followed by abrupt DNA breaks and activation of homologous recombinant and nonhomologous end joining DNA repair, along with the enhancement of apoptosis. Mice in different stages of the hair cycle were sacrificed, and the dorsal skins were collected. The results of western blot and histological staining indicated that AIF-PARP1 plays a key role in HF apoptosis, but their role in the regulation of the HF cycle is not clear. Mice were treated with inhibitors from anagen to catagen: treatment with BMN 673, a PARP1 inhibitor, increased DNA breaks and activated the cytochrome c/caspase-3-mediated apoptotic pathway, accelerating HF regression. Ac-DEVD-CHO (Ac), a caspase-3 inhibitor, attenuated HF degeneration by upregulating PARP1 expression, suggesting a seesaw relationship between cytochrome c-caspase-3- and AIF-PARP1-mediated apoptosis, wherein PARP1 may be the fulcrum. In addition, macrophages were involved in regulating the hair cycle, and the rate of M1 macrophages around HFs increased during catagen, while more M2 macrophages were found during anagen and telogen. Our results indicate that intrinsic ROS drive HF cycle progression through DNA damage and repair, followed by apoptosis. Intrinsic ROS drive hair follicle cycle progression by modulating DNA damage and repair, and consecutively, hair follicle apoptosis and macrophage polarization work together to promote the hair follicle cycle.
Path Planning and Trajectory Tracking for Automatic Guided Vehicles
Authors: Tang Yongwei , Zhou Jun , Hao Huijuan , Hao Fengqi , Xu Haigang
Published: July 2022

Automated guided vehicle technology has become a hot area of scientific research due to its increasing use in manufacturing and logistics. Its main features are programming and control, remote computer eye tracking, command receiving and execution, autonomous route planning, and autonomous driving execution of tasks, with the advantages of high intelligence and flexibility. In this work, a simple vehicle model is used to study the route planning and tracking control of automatic guided vehicles. This paper uses wireless communication to find the optimal route planning problem. Using geometric methods, we develop a model of the working environment of the mobile automatic guided vehicle and develop a route finding algorithm. Based on the kinematic model, an advanced routing controller is designed to conduct experimental simulation of two trajectories and verify the effectiveness of the trajectory tracking controller. When the time is after 2 s, the position error is almost completely zero. In the path planning, when the number of iterations is greater than 10, the path length remains constant, verifying the effectiveness of the method in this paper.
Preparation of Molecular Imprinted Polymer Based on Chitosan as the Selective Sorbent for Solid-Phase Microextraction of Phenobarbital
Authors: Rahimi Marzieh , Bahar Soleiman , Amininasab S. Mojtaba
Published: July 2022

This study reports the construction of a novel SPME fiber based on chitosan and glutaraldehyde as coating material composites combined with high-performance liquid chromatography with an ultraviolet detector (HPLC-UV) for extraction and detection of phenobarbital. In this technique, the chitosan biopolymer, as a new coating of SPME fiber, was produced on the stainless-steel wire, using glutaraldehyde and phenobarbital as cross-linker and template, respectively. For comparison, a nonimprinted polymer was created using the same procedure to evaluate fiber selectivity (but without the addition of phenobarbital). The SPME-MIP fiber coating was characterized by field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, and thermal gravimetric analysis. The efficiency of fiber was then improved by adjusting the impact of numerous factors such as pH, extraction time, desorption time, desorption solvent, and stirring rate. The results showed that the proposed fiber has a linear range of 0.01–4 μg·mL−1, and detection limit of 7.5 ng·mL−1. The average recoveries in the four concentration levels for the spiked river and well water samples were 95.7 and 95.3%, with relative standard deviations of 3.8 and 5.9% for single fiber and between fibers, respectively.
A Study of How Moral Courage and Moral Sensitivity Correlate with Safe Care in Special Care Nursing
Authors: Mohammadi Fateme , Tehranineshat Banafsheh , Ghasemi Afsaneh , Bijani Mostafa
Published: July 2022

Background. Nursing is a caring profession, and nurses who have moral sensitivity and moral courage presumably can provide safe and better care for patients. This study aims at investigating how moral courage and moral sensitivity correlate with safe care in special care nursing. Methods. This study is a descriptive work of research. The participants consisted of 524 nurses who were in practice in the ICU (intensive care unit), CCU (C\coronary care unit), post-CCU (postcoronary care unit), and dialysis of four hospitals located in the south of Iran selected via census sampling. Data were collected from April to September 2020 using the moral sensitivity questionnaire (MSQ), professional moral courage questionnaire (PMCQ), and the assessment of safe nursing care questionnaire (ASNCQ). The collected data were analyzed using descriptive statistics, t-test, chi-square, multiple regression analysis, and Pearson’s correlation coefficient in SPSS v. 22. Results. The mean ± SD of the nurses’ age was 33.89 ± 6.91 years, and the mean ± SD of their work experience was 9.16 ± 4.67 years. The total mean score ± SD of the nurses’ moral sensitivity was found to be 93.41 ± 2.68, the total mean score ± SD of their moral courage was found to be 96.38 ± 3.63, and the total mean score ± SD of their safe care scores was found to be 321.80 ± 9.76. The values of Pearson’s correlation coefficients showed significant correlations between moral courage and safe care (r = 0.54,

p
<
0.001

), moral sensitivity and safe care (r = 0.59,

p
<
0.001

), and moral sensitivity and moral courage (r = 0.52,

p
<
0.001

). Conclusion. There is a positive correlation between moral sensitivity and moral courage. Both positively correlated with special care nursing. Accordingly, through effective planning, education, and giving their support, nurse administrators can promote the abovementioned ethical virtues in the nursing staff, thereby improving the quality of care.
Classification Method of Ideological and Political Resources of Broadcasting and Hosting Professional Courses Based on SOM Artificial Neural Network
Authors: Si Wenwen
Published: July 2022

In order to improve the classification effect of ideological and political resources of audio hosting professional courses and improve the classification accuracy of ideological and political resources of courses, this paper puts forward a classification method of ideological and political resources of broadcasting and hosting professional courses based on SOM artificial neural network. The adaptive sliding window mutual information method is used to extract the sample characteristics of ideological and political resources of broadcasting and hosting professional courses. This paper constructs the classification model of ideological and political resources of broadcasting and hosting professional courses through deep belief neural network, designs the ideological and political resources classifier of broadcasting and hosting professional courses according to SOM artificial network, constructs the ideological and political resources feature tree of broadcasting and hosting professional courses, and obtains the leaf nodes of the feature tree through hierarchical aggregation algorithm. The category of ideological and political resources of broadcasting and hosting professional courses is obtained by using the merging processing method, the classification operation results are verified by BIC criterion, the number of clusters with the maximum growth distance, that is, the final number of clusters, is calculated and brought into the classifier, and the classification results of SOM artificial network classifier are output to realize the classification of ideological and political resources of broadcasting and hosting professional courses. The experimental results show that, under this method, the accuracy of ideological and political resources classification of broadcasting and hosting professional courses can reach 99.18%, and the completeness is as high as 99.58%, and the F-measure value is effectively improved, which shows that this method can improve the effect of ideological and political resources classification of broadcasting and hosting professional courses.
Influence of Intelligent Internet of Things Technology on Taekwondo Athletes’ Competitive Ability
Authors: Chen Shiqiang , Chen Hui
Published: July 2022

To maintain an advantage in the development of competitive sports, a country should explore the gap between Taekwondo athletes and other elite athletes. By comparing and analyzing to find out the reasons, it can create favorable conditions for the project and strive for greater advantages, which is the top priority for the project to develop. The purpose of this paper is to use the intelligent Internet of Things technology to analyze the factors affecting the competitive ability of Taekwondo athletes. Aiming at the competitive ability of Taekwondo, it analyzes the three aspects of psychological ability, technical ability, and tactical ability to construct a model of Taekwondo athletes’ competitive ability. And for the indicators in the model, the intelligent Internet of Things technology is used to detect them in real time to achieve the best model construction effect. The experiment of this paper found that the competitive ability model of Taekwondo athletes’ combining psychological ability, technical ability, and tactical ability is relatively successful. The Taekwondo competitive ability of athletes based on model analysis is almost the same as the competitive ability scored by experts, and the error is within 5%. It shows that psychological ability, tactical ability, and technical ability have important influence on the competitive ability of Taekwondo.
Post-Quantum Secure Password-Authenticated Key Exchange Based on Ouroboros
Authors: Wang Hao , Li Yu , Wang Li-Ping
Published: July 2022

Password-authenticated key exchange (PAKE) protocols play an important role in cryptography. Most of PAKEs are based on the Diffie–Hellman key exchange protocols or RSA encryption schemes, but their security is threatened by quantum computers. In this study, we propose the first code-based PAKE protocol based on Ouroboros, which is a code-based key exchange protocol. Our scheme enjoys high efficiency and provides mutual explicit authentication, with a security reduction to decoding random quasi-cyclic codes in the random oracle model.
Effects of Bevacizumab Combined with Chemotherapy on CT, CyFRA21-1, and ProGRP and Prognosis of Lung Cancer Patients under Nursing Intervention
Authors: Xi Chao , Jiang Hong , Xue Yinling , Lv Yongmei , Wang Chao
Published: July 2022

Objective. Molecular targeted drug therapy and chemotherapy are the main treatments for advanced non-small-cell lung cancer, and the combination of both has advantages in prolonging patients’ progression-free survival and overall survival. This study investigated the effects of bevacizumab combined with chemotherapy under nursing intervention on CT, cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and gastrin-releasing peptide precursor (ProGRP) and prognosis of lung cancer patients. Methods. 102 patients with non-small-cell lung cancer admitted to our hospital from January 2018 to May 2019 were divided into observation group and control group, with 51 cases each. The control group was treated with basic chemotherapy, and the observation group was treated with bevacizumab in combination with the control group, and both groups used nursing interventions. The clinical effects, CYFRA21-1 and ProGRP levels, baseline data, CT parameters, 24-month cumulative survival, and the effects of CYFRA21-1 and ProGRP on long-term survival and lung function were compared. Results. The disease control rate of the observation group was 94.12%, which was significantly higher than that of the control group (76.47%); after 7 d, 30 d, 60 d, and 90 d of treatment, the levels of CYFRA21-1 and ProGRP were statistically downregulated. The difference in lymph node metastasis, lesion diameter, plain Eff-Z, venous stage, and arterial stage normalized iodine concentrations (NIC) was statistically significant; the survival rate at 24 months in the observation group was 74.51% (38/51); the cumulative survival rate at 24 months in the control group was 52.94% (27/51), and the difference was statistically significant (

X

2

=
4.980

,

P
=
0.026

). The cumulative survival rate at 24 months was significantly lower in patients with high expression of CYFRA21-1 and ProGRP compared with those with low expression of CYFRA21-1 and ProGRP. After treatment, in the observation group, the forceful spirometry (FVC), forceful expiratory volume in one second (FEV1), and FEV1/FVC levels were significantly different from those before treatment and were significantly different from those in the control group. Conclusion. Bevacizumab in combination with standard chemotherapy regimens with nursing interventions could benefit patients with advanced non-small-cell lung cancer and had a good prospect of application.
Neoadjuvant Trastuzumab and Pyrotinib for Locally Advanced HER2-Positive Breast Cancer (NeoATP): Primary Analysis of a Phase II Study
Authors: Yin Wenjin , Wang Yaohui , Wu Ziping , Ye Yumei , Zhou Liheng , Xu Shuguang , Lin Yanping , Du Yueyao , Yan Tingting , Yang Fan , Zhang Jie , Liu Qiang , Lu Jinsong
Published: July 2022

Purpose:

Despite accumulating evidence on dual blockade of HER2 for locally advanced HER2-positive breast cancer, no robust evidence supports the addition of pyrotinib to trastuzumab in the neoadjuvant setting. The NeoATP trial aimed to evaluate the efficacy and safety of pyrotinib with neoadjuvant trastuzumab and chemotherapy.

Patients and Methods:

The phase II NeoATP trial included female patients with histologically confirmed stage IIA to IIIC and HER2-positive primary invasive breast cancer. Eligible patients received pyrotinib and trastuzumab with weekly paclitaxel–cisplatin neoadjuvant chemotherapy for four cycles. The primary endpoint was pathologic complete response (pCR; ypT0 ypN0) rate. Key secondary endpoints included locoregional pCR (ypT0/is ypN0) rate, biomarker analysis, and safety.

Results:

Among 53 enrolled patients (median age, 47 years; 73.58% stage III), 52 completed the study treatment and surgery. Overall, 37 patients (69.81%) achieved pCR. For women with hormone receptor–negative and –positive tumors, the pCR rates were 85.71% and 59.38% (P = 0.041), while the corresponding rates were 69.23% and 70.00%, respectively, for those with and without PIK3CA mutation (P = 0.958). The most frequently reported Grade 3 to 4 adverse events were diarrhea (45.28%), leukopenia (39.62%), and neutropenia (32.08%). No deaths occurred, and no left ventricular ejection fraction <50% or >10 points drop from baseline to before surgery was reported.

Conclusions:

The addition of pyrotinib to trastuzumab plus chemotherapy is an efficacious and safe regimen for patients with HER2-positive locally advanced breast cancer in the neoadjuvant setting. The randomized controlled clinical trial is warranted to validate our results.
Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer
Authors: Ruggieri Amanda N. , Yarchoan Mark , Goyal Subir , Liu Yuan , Sharon Elad , Chen Helen X. , Olson Brian M. , Paulos Chrystal M. , El-Rayes Bassel F. , Maithel Shishir K. , Azad Nilofer S. , Lesinski Gregory B.
Published: July 2022

Purpose:

Biliary tract cancers (BTC) are aggressive malignancies refractory to chemotherapy and immunotherapy. MEK inhibition (MEKi)-based regimens may have utility in this disease when combined with PD-L1 blockade. We hypothesize that dual MEK/PD-L1 inhibition alters circulating soluble and cellular immune mediators to improve clinical outcomes in patients with advanced BTC.

Experimental Design:

We examined immune features in peripheral blood from 77 patients with advanced BTC enrolled in a phase II clinical trial investigating atezolizumab with or without cobimetinib. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from whole blood to evaluate soluble factors and immune cell populations. Baseline blood samples were additionally compared with healthy donors to identify immune signatures unique to BTC.

Results:

At baseline, the soluble factors platelet-derived growth factor B (PDGF)-BB, placental growth factor (PlGF)-1, IL5, and IL17A were elevated in patients with BTC compared with healthy adult donors, and higher baseline frequencies of CD8+BTLA+ T cells correlated with better overall survival (OS) in this trial. There were also significant treatment-related alterations in several factors, including decreased PDGF-BB following combination treatment, that correlated with improved OS and progression-free survival (PFS). Higher baseline levels of IL23 and RANTES corresponded to improved clinical outcomes following combination treatment. Dual MEK/PD-L1 inhibition increased populations of CD4+TIM3+ and decreased CD8+VISTA+ T cells, correlating with worse OS and better PFS, respectively.

Conclusions:

This work represents a comprehensive analysis of peripheral immune features in patients with BTC and systemic responses to dual MEK/PD-L1 inhibition. These data support further investigation to understand how MEKi combines with immunotherapeutic approaches to improve clinical outcomes for patients with advanced BTC.
A Phase I Trial of TB-403 in Relapsed Medulloblastoma, Neuroblastoma, Ewing Sarcoma, and Alveolar Rhabdomyosarcoma
Authors: Saulnier-Sholler Giselle , Duda Dan G. , Bergendahl Genevieve , Ebb David , Snuderl Matija , Laetsch Theodore W. , Michlitsch Jennifer , Hanson Derek , Isakoff Michael S. , Bielamowicz Kevin , Kraveka Jacqueline M. , Ferguson William , Carmeliet Peter , De Deene A. , Gijsen Lore , Jain Rakesh K.
Published: July 2022

Purpose:

Placental growth factor (PlGF) and its receptor neuropilin 1 are elevated in malignant embryonal tumors and mediate tumor progression by promoting cell proliferation, survival, and metastasis. TB-403 is a blocking monoclonal antibody against PlGF that inhibits tumor growth and increases survival in orthotopic medulloblastoma models.

Patients and Methods:

We conducted a phase I, open-label, multicenter, dose-escalation study of TB-403 in pediatric subjects with relapsed or refractory cancers. The study involved four dose levels (20 mg/kg, 50 mg/kg, 100 mg/kg, 175 mg/kg) using a 3 + 3 dose-escalation scheme. Subjects received two doses of TB-403 (days 1 and 15) per cycle. After cycle 1, temozolomide or etoposide could be added. The primary objective was to determine the maximum tolerated dose (MTD) of TB-403 monotherapy during a dose-limiting toxicity assessment period. The secondary and exploratory objectives included efficacy, drug pharmacokinetics, and detection of pharmacodynamic biomarkers.

Results:

Fifteen subjects were treated in four dose levels. All subjects received two doses of TB-403 in cycle 1. Five serious treatment-emergent adverse events were reported in 3 subjects, but MTD was not reached. While no complete nor partial responses were observed, 7 of 11 relapsed subjects with medulloblastoma experienced stable disease, which persisted for more than 100 days in 4 of 7 subjects.

Conclusions:

TB-403 was safe and well tolerated at all dose levels. No MTD was reached. The results look encouraging and therefore warrant further evaluation of efficacy in pediatric subjects with medulloblastoma.
Safety and Efficacy of 90Y-FAPI-46 Radioligand Therapy in Patients with Advanced Sarcoma and Other Cancer Entities
Authors: Fendler Wolfgang P. , Pabst Kim M. , Kessler Lukas , Fragoso Costa Pedro , Ferdinandus Justin , Weber Manuel , Lippert Maria , Lueckerath Katharina , Umutlu Lale , Kostbade Karina , Mavroeidi Ilektra A. , Schuler Martin , Ahrens Marit , Rischpler Christoph , Bauer Sebastian , Herrmann Ken , Siveke Jens T. , Hamacher Rainer
Published: July 2022

Purpose:

We report efficacy and safety of 90Y-labeled FAPI-46 (90Y-FAPI-46-RLT) in patients with advanced sarcoma, pancreatic cancer, and other cancer entities.

Experimental Design:

Up to four cycles of radioligand therapy (RLT) were offered to patients with (i) progressive metastatic malignancy, (ii) exhaustion of approved therapies, and (iii) high fibroblast activation protein (FAP) expression, defined as SUVmax ≥ 10 in more than 50% of tumor. Primary endpoint was RECIST response after RLT. Secondary endpoints included PET response (PERCIST), overall survival (OS), dosimetry, and safety of FAP-RLT.

Results:

Among 119 screened patients, 21 (18%) were found eligible [n = 16/3/1/1 sarcoma/pancreatic cancer/prostate/gastric cancer; 38% Eastern Cooperative Oncology Group (ECOG) ≥ 2] and received 47 90Y-FAPI-46-RLT cycles; 16 of 21 (76%) patients underwent repeat RLT. By RECIST, disease control was confirmed in 8 of 21 patients [38%; 8/16 (50%) of evaluable patients). There was one partial response (PR) and seven stable diseases after RLT. Disease control was associated with prolonged OS (P = 0.013). PERCIST response was noted in 8 of 21 patients [38%; 8/15 (53%) of evaluable patients]. Dosimetry was acquired in 19 (90%) patients. Mean absorbed dose was 0.53 Gy/GBq in kidney, 0.04 Gy/GBq in bone marrow, and <0.14 Gy/GBq in liver and lung. Treatment-related grade 3 or 4 adverse events were observed in 8 (38%) patients with thrombocytopenia (n = 6) and anemia (n = 6) being most prevalent.

Conclusions:

90Y-FAPI-46-RLT was safe and led to RECIST PR in one case as well as stable disease in about one third of patients with initially progressive sarcomas, pancreatic cancer, and other cancers. Discontinuation after the first cycle and a low rate of PR requires future improvement of FAP-RLT.
Elevated Mutational Age in Blood of Children Treated for Cancer Contributes to Therapy-Related Myeloid Neoplasms
Authors: Bertrums Eline J.M. , Rosendahl Huber Axel K.M. , de Kanter Jurrian K. , Brandsma Arianne M. , van Leeuwen Anaïs J.C.N. , Verheul Mark , van den Heuvel-Eibrink Marry M. , Oka Rurika , van Roosmalen Markus J. , de Groot-Kruseman Hester A. , Zwaan C. Michel , Goemans Bianca F. , van Boxtel Ruben
Published: July 2022

Childhood cancer survivors are confronted with various chronic health conditions like therapy-related malignancies. However, it is unclear how exposure to chemotherapy contributes to the mutation burden and clonal composition of healthy tissues early in life. Here, we studied mutation accumulation in hematopoietic stem and progenitor cells (HSPC) before and after cancer treatment of 24 children. Of these children, 19 developed therapy-related myeloid neoplasms (t-MN). Posttreatment HSPCs had an average mutation burden increase comparable to what treatment-naïve cells accumulate during 16 years of life, with excesses up to 80 years. In most children, these additional mutations were induced by clock-like processes, which are also active during healthy aging. Other patients harbored mutations that could be directly attributed to treatments like platinum-based drugs and thiopurines. Using phylogenetic inference, we demonstrate that most t-MN in children originate after the start of treatment and that leukemic clones become dominant during or directly after chemotherapy exposure.

Significance:

Our study shows that chemotherapy increases the mutation burden of normal blood cells in cancer survivors. Only few drugs damage the DNA directly, whereas in most patients, chemotherapy-induced mutations are caused by processes similar to those present during normal aging.
Roles for SGLT2 Inhibitors in Cardiorenal Disease
Authors: Green Jennifer B. , McCullough Peter A.
Published: July 2022

Introduction: Cardiovascular (CV) disease and chronic kidney disease (CKD) share common risk factors, including type 2 diabetes mellitus (T2DM). In CV outcome studies of patients with T2DM, sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy was associated with risk reductions in cardiorenal endpoints. This article aims to provide a comprehensive overview of the efficacy of SGLT2i therapy in patients at risk of cardiorenal disease. Methods: A literature review of large outcome studies of patients who had CKD or heart failure with reduced ejection fraction (HFrEF, defined as having a left ventricular ejection fraction [LVEF] <40%) or heart failure with preserved ejection fraction (LVEF ≥50%) was undertaken to evaluate the associations between SGLT2i use and cardiorenal events. Results: In the cardiorenal outcome studies, patients with CKD who received canagliflozin or dapagliflozin had a lowered risk of a sustained decline in kidney function, end-stage kidney disease, or death from renal or CV causes than patients who received placebo. In outcome studies that enrolled patients with HFrEF, dapagliflozin, empagliflozin, and sotagliflozin lowered the risk of the composite endpoint of CV death and hospitalization for heart failure (HHF) versus placebo, an effect driven largely by a reduced risk of HHF. SGLT2i therapy was associated with risk reductions in the CV death/HHF composite and stand-alone HHF endpoints in patients with CKD. Conversely, patients with HFrEF attained renal benefit from SGLT2i use. Conclusion: The efficacy of SGLT2i was observed across a diverse range of patient subgroups. SGLT2i therapy has been found to substantially mitigate cardiorenal morbidity in patients with CKD or HFrEF, regardless of the presence of T2DM and severity of CKD or HF.
Within-Visit Blood Pressure Variability and All-Cause and Stroke Mortality: Thai Epidemiologic Stroke Study
Authors: Hanchaiphiboolkul Suchat , Puthkhao Pimchanok , Tantirittisak Tasanee , Na Songkhla Krida , Komonchan Surasak , Worakijthamrongchai Thanaboon , Thiraworawong Thon
Published: July 2022

Introduction: The association between within-visit blood pressure variability (BPV) and all-cause and stroke mortality remains uncertain. The aim of our study was to assess the association of within-visit BPV with all-cause and stroke mortality. Methods: The study was conducted among participants from Thai Epidemiologic Stroke Study, which is a prospective community-based cohort study that recruited participants from the general population from five regions of Thailand. This study included 19,614 participants aged 45–80 years, who were free of stroke and had three blood pressure (BP) measurements, taken 1 min apart, at baseline. Within-visit systolic blood pressure (SBP) and diastolic blood pressure (DBP) variability were expressed as the maximum absolute difference (MAD) between any two readings among the three repeated sequential measurements of SBP and DBP, respectively. The participants were followed up for mortality. Cox regression analysis was used to identify the association of within-visit BPV with all-cause and stroke mortality. Hazard ratio (HR) and 95% confidence intervals were used to illustrate the associations. Sensitivity analysis restricted to participants with mean SBP above 130 mm Hg and mean DBP above 90 mm Hg (n = 1,895) was performed. Results: During a median follow-up of 11.1 years, 305 participants died of stroke, and 3,173 participants died of nonstroke cause. In unadjusted analyses, high within-visit MAD of SBP was significantly associated with all-cause (HR, 1.19; 95% CI, 1.09–1.31; p < 0.001) and stroke mortality (HR, 1.87; 95% CI, 1.35–2.59; p < 0.001); high within-visit MAD of DBP was also significantly associated with all-cause mortality (HR, 1.19; 95% CI, 1.08–1.31; p < 0.001), in quartile 4 versus quartile 1. These associations did not persist after further adjustment for sex, age, and other potential confounders including mean BP. However, sensitivity analysis showed some inconsistent results regarding associations of within-visit MAD of SBP and DBP with all-cause and stroke mortality, respectively. Conclusion: In general population, within-visit systolic BPV and within-visit diastolic BPV do not have prognostic significance on stroke mortality and all-cause mortality, respectively.
The Link between Anterior Scleral Thickness, Corneal Biomechanical Response, and Ocular Parameters
Authors: Burguera-Giménez Neus , Díez-Ajenjo M. Amparo , Burguera Noemí , Luque-Cobija M. José , Peris-Martínez Cristina
Published: July 2022

Introduction: This study aimed to assess anterior scleral thickness (AST) across diverse scleral meridians and to evaluate the relationship with corneal biomechanical response and several ocular parameters. Methods: This prospective nonrandomized study comprised 50 eyes of 50 patients (mean age, 29.02 ± 9.48 years). AST was measured meridionally at three scleral locations (1, 2, and 3 mm posterior to the scleral spur) using swept-source optical coherence tomography. A multivariate model was created to associate AST with several ocular parameters. Principal component analysis (PCA) was used to reduce linearly the dimensionality of seven biomechanical input metrics to two significant components, C1 and C2. Two multivariate analyses were performed to associate C1 and C2 with AST and ocular parameters. Results: AST was thickest in the inferior (581 ± 52 µm) and thinnest in the superior meridian (441 ± 42 µm) when compared to all meridians (p < 0.001) and similar in the nasal (529 ± 53 µm) and temporal (511 ± 59 µm) meridians (p > 0.05). The sclera exhibited the thinnest point 2 mm posterior to the scleral spur (p < 0.001). The AST was significantly linked with axial length, central corneal thickness, and intraocular pressure (p < 0.001). The PCA showed that C1 accounts for 53.84%, whereas C2 for the 16.51% of the total variance in the original variables. The C1 model was significantly associated with AST along all meridians (p < 0.001). The partial correlation was moderate in the nasal (r = −0.36, p < 0.001) and inferior (r = −0.26, p = 0.004) meridians, whereas weak in the temporal (r = −0.14, p = 0.05) and superior (r = −0.15, p = 0.05) meridians. Conclusions: The relationship between the new biomechanical component and the AST provides the first evidence of the association of AST with the corneal response parameters which should be considered in corneal response interpretation. Tissue thickness varied significantly among meridians supporting the asymmetrical expansion of the ocular globe. The AST was associated with several ocular parameters.
Prevalence of Burnout in Portuguese Public Health Medical Residents amid the Response to the COVID-19 Pandemic
Authors: Viana Diogo Sampaio , Teixeira Paula , Ferreira Eduarda
Published: July 2022

Introduction: Burnout is a psychological syndrome characterized by a state of emotional exhaustion, depersonalization, and a lack of personal accomplishment at the workplace. We aimed to evaluate the prevalence of burnout among Portuguese Public Health Medical Residents during the SARS-CoV-2 virus pandemic. Methods: Burnout was assessed with the Maslach Burnout Inventory – Human Services Survey, using a zero (never) to six (always) ordinal scale. Sociodemographic and workplace setting data were also collected. Categorical variables were presented as frequencies and percentages, and continuous variables as means and standard deviations (SDs). Chi-squared and independent sample t tests were used to evaluate the distributions of these variables, with a p value of 0.05. Results: Eighty-three people participated. The average age was 30.46 (±3.91), and 57.8% were female. We found that 77.11% had high levels of emotional exhaustion, 61.4% had high levels of depersonalization, and 44.6% had low levels of personal accomplishment. 32.5% of the participants were experiencing burnout, 30.5% were at high risk, 25.3% were at moderate risk, and 12% were at low risk. Burned-out participants had higher levels of emotional exhaustion (40.63 ± 7.36; mean ± SD) and depersonalization (15.63 ± 5.94; mean ± SD), and lower levels of personal achievement (29.42 ± 7.30; mean ± SD) than their peers. Regarding sociodemographic and work setting-related data, no statistically significant differences were found between professionals with and with no burnout. Conclusion: The present study shows high scores on all components of burnout and its prevalence among the population studied. Further studies are needed to determine whether this phenomenon was specific to this period.
Severe Toxic Epidermal Necrolysis and Drug Reaction with Eosinophilia and Systemic Symptoms Overlap Syndrome Treated with Benralizumab: A Case Report
Authors: Zeller Felix K. , Bader Patrick R. , Nägeli Mirjam C. , Buehler Philipp K. , Schuepbach Reto A.
Published: July 2022

TEN/DRESS overlap syndrome can be difficult to diagnose, especially if it is masked by comorbidities in critically ill patients in intensive care units. The existing therapy for the two conditions is also a major challenge for the treating team. A possible alternative, especially for refractory cases, is benralizumab as an IL-5-receptor alpha-chain-specific humanized monoclonal antibody (IgG1k). We are able to show a successful treatment in this case report.
Amnioinfusion versus Usual Care in Women with Prelabor Rupture of Membranes in Midtrimester: A Systematic Review and Meta-Analysis of Short- and Long-Term Outcomes
Authors: de Ruigh Annemijn A. , Simons Noor E. , van der Windt Larissa I. , Breuking Sofie H. , van ‘t Hooft Janneke , van Teeffelen Augustinus S. , Alfirevic Zarko , Roberts Devender , Mol Ben W. , Pajkrt Eva
Published: July 2022

Introduction: Midtrimester prelabor rupture of membranes (PROM) between 16 and 24 weeks of gestational age is a major obstetric complication with high rates of perinatal morbidity and mortality. Amnioinfusion has been proposed in women with midtrimester PROM to target oligohydramnios and subsequently enhance pulmonary development and perinatal outcomes. Material and Methods: The purpose of this study was to perform a systematic review and meta-analysis including all randomized clinical trials investigating amnioinfusion versus no intervention in women with PROM between 16+0 and 24+0 weeks of gestational age. Databases Central, Embase, Medline, ClinicalTrials.gov and references of identified articles were searched from inception of database to December 2021. The primary outcome was perinatal mortality. Secondary outcomes included neonatal, maternal, and long-term developmental outcomes as defined in the core outcome set for preterm birth studies. Summary measures were reported as pooled relative risk (RR) or mean difference with corresponding 95% confidence interval (CI). Results: Two studies (112 patients, 56 in the amnioinfusion group and 56 in the no intervention group) were included in this review. Pooled perinatal mortality was 66.1% (37/56) in the amnioinfusion group compared with 71.4% (40/56) in no intervention group (RR 0.92, 95% CI: 0.72–1.19). Other neonatal and maternal core outcomes were similar in both groups, although due to the relatively small number of events and wide CIs, there is a possibility that amnioinfusion can be associated with clinically important benefits and harms. Long-term healthy survival was seen in 35.7% (10/28) of children assessed for follow-up and treated with amnioinfusion versus 28.6% (8/28) after no intervention (RR 1.30, 95% CI: 0.47–3.60, “best case scenario”). Conclusions: Based on these findings, the benefits of amnioinfusion for midtrimester PROM <24 weeks of gestational age are unproven, and the potential harms remain undetermined.