bluuebunny/crossref_metadata_2025 huggingface dataset:
[Retracted] Experimental Analysis of the Effect of Rehabilitation Intervention on Tennis Players by Joint Injury Treatment
Authors: Ma Ligang , Yu Xuedou , He Ruihua , Gao Yakun , Li Xiaoliang
Published: June 2022

In the process of competition and training, tennis players often carry out explosive force and extreme centripetal and eccentric contraction, while the ligament and joint capsule on the shoulder joint are relatively weak, which also makes the joint often appear injury caused by overuse. It has been the direction of scientific research to help athletes recover their functions and return to the arena through effective rehabilitation training and prerehabilitation training. In this paper, the reliability and short‐term effect of wearing dynamic and static shoulder joint brace after arthroscopic repair of rotator cuff injury were studied through a controlled trial of tennis exercise for the treatment of shoulder injury. The purpose of this study was to apply the dynamic and static shoulder joint brace to patients with rotator cuff injury and shorten the recovery time of shoulder joint function the operation. This paper also studies the therapeutic effect verification of patients with rotator cuff injury during rehabilitation period by wearing shoulder joint brace with dynamic and static combination. Through the comparison between the experimental group and the control group, it is verified that the effect of rehabilitation intervention is better than that of the control group, which shows that the use of dynamic and static shoulder joint brace can improve the range of motion of shoulder joint and patient satisfaction, and the effect increases with time. This study improves the shoulder strength of tennis players through functional training, demonstrates the value and significance of functional training for the development of tennis through experiments, and provides a reference for athletes to improve their physical fitness training. At the same time, the research content of this paper can also provide references and promotion for sports events.
Characteristics and Outcomes of Shared Bicycle-Related Injuries from a Large Emergency Medical Centre in China, 2017–2021
Authors: Chen Mao , Li Weiwei , Ye Jun , Liu Gang , Huang Chaolin
Published: June 2022

Objective. The aim of this study is to investigate the characteristics and outcomes of shared bicycle-related injuries from a large emergency medical centre in China in five years from January 2017 to December 2021. Methods. This study was conducted by reviewing the electronic medical record database of a large hospital in China for cases of shared bicycle-related injuries in five years from January 2017 to December 2021. The collected information included demographic data, injury characteristics, and outcomes. Multivariate logistic regression analysis was used to identify risk factors for fatal injury among victims. Results. Most shared bicycle-related injuries occurred in male (60.50%), aged 18–35 (38.81%). Company employees (29.28%) were the majority of victims of shared bicycle-related injuries. Riding in a motor vehicle lane was the most common unsafe riding behaviour (26.52%). The lower limb was the most frequently injured body region (25.28%). Bruising (28.73%) was the most commonly diagnosed injury type. The fatality rate was 9.53%, 72.24% of victims recovered well without permanent disability, and 18.23% of victims had permanent disabilities. The length of hospital stay of most of the victims (67.54%) was less than 7 days, and the hospitalization cost of most of the victims (51.93%) was less than 20,000 Yuan. Riding in a motor vehicle lane, running red lights, and cycling against traffic flow are risk factors for fatal injury. Conclusions. This study indicated that shared bicycle-related injuries make up a sizeable proportion of injuries presenting to the emergency department and with diverse injury characteristics and outcomes. The findings reflect that shared bicycle-related injury has become a public health problem. Therefore, it is necessary to establish injury prevention strategies for the safety of shared bicycle users.
ERRγ, a Novel Biomarker, Associates with Pathoglycemia of Endometrial Cancer to Predict Myometrial Invasion
Authors: Tong Yao , Huang Meimei , Chen Lili , Lei Huifang , Lin Hao , Mao Xiaodan , Sun Pengming
Published: June 2022

We aim to investigate the correlation between the expression of estrogen-related receptor γ (ERRγ) and endometrial cancer (EC) progression and to evaluate the potential of ERRγ as a new biomarker for EC diagnosis. We analyzed the ERRγ expression profile and the correlation with the corresponding clinical characteristics of EC samples from The Cancer Genome Atlas (TCGA), the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, and the International Cancer Genome Consortium (ICGC) databases. Immunohistochemical (IHC) analysis was conducted on tissue samples, and enzyme linked immunosorbent assay (ELISA) was used in serum samples to detect the levels of ERRγ. The diagnostic performance of ERRγ proteins was assessed using the receiver operating characteristic (ROC). ERRγ showed notably higher expression in EC tissues than in normal endometrium tissues (

P
<
0.001

), which was consistent with the result of TCGA. Overexpression of ERRγ was significantly associated with deep myometrial invasion of EC (

P
=
0.004

), and fasting blood glucose (FBG) was higher in EC patients with deep myometrial invasion than in those with superficial myometrial invasion (

P
=
0.040

). Further analysis using ELISA showed that the serum ERRγ level was positively correlated with FBG (R = 0.355,

P
<
0.001

). ERRγ is overexpressed in EC and may be involved in regulating glucose metabolism and promoting myometrial invasion of EC. In addition, the area under the ROC curve (AUC) for ERRγ was 0.834, in distinguishing EC patients from healthy individuals, presented 84.0% and 80.0% sensitivity and specificity, respectively, and serum ERRγ has a good diagnostic performance in distinguishing EC patients from healthy people and may be a promising noninvasive biomarker in EC.
Metabolic Syndrome: Lessons from Rodent and Drosophila Models
Authors: Vatashchuk Myroslava V. , Bayliak Maria M. , Hurza Viktoria V. , Storey Kenneth B. , Lushchak Volodymyr I.
Published: June 2022

Overweight and obesity are health conditions tightly related to a number of metabolic complications collectively called “metabolic syndrome” (MetS). Clinical diagnosis of MetS includes the presence of the increased waist circumference or so‐called abdominal obesity, reduced high density lipoprotein level, elevated blood pressure, and increased blood glucose and triacylglyceride levels. Different approaches, including diet‐induced and genetically induced animal models, have been developed to study MetS pathogenesis and underlying mechanisms. Studies of metabolic disturbances in the fruit fly Drosophila and mammalian models along with humans have demonstrated that fruit flies and small mammalian models like rats and mice have many similarities with humans in basic metabolic functions and share many molecular mechanisms which regulate these metabolic processes. In this paper, we describe diet‐induced, chemically and genetically induced animal models of the MetS. The advantages and limitations of rodent and Drosophila models of MetS and obesity are also analyzed.
Composting and Anaerobic Digestion of Food Waste and Sewage Sludge for Campus Sustainability: A Review
Authors: Yaser Abu Zahrim , Lamaming Junidah , Suali Emma , Rajin Mariani , Saalah Sariah , Kamin Zykamilia , Safie Nurliyana Nasuha , Aji Nur Aqeela Syuhadah , Wid Newati
Published: June 2022

Composting and anaerobic digestion have emerged as better options for managing food waste and sewage sludge at the campus level. This review highlights the characteristics of food waste and sewage sludge from various global higher education institutions. The composting and anaerobic digestion processes of food waste and sewage sludge will be reviewed and evaluated. Also, the adoption of composting and anaerobic digestion at various campus levels has been reviewed. The challenges and future direction, focusing on managing university campus composting and anaerobic digestion, are discussed as well. This review paper will significantly contribute to the understanding of the potential for managing and handling campus waste in a natural-friendly manner.
Research on Cavitation Flow Dynamics and Entropy Generation Analysis in an Axial Flow Pump
Authors: Shen Simin , Huang Bensheng , Huang Si , Xu Shun , Liu Shufeng
Published: June 2022

The entropy generation theory is introduced to investigate the effects of different NPSH and tip clearance size on the cavitation flow dynamics and mechanical energy dissipation intuitively and quantitatively within an axial flow pump through numerical simulations. The results indicate that main mechanical energy dissipation of the pump gathers in part impeller and diffuser, and most are turbulent dissipation. Meanwhile, the impeller is the largest place of mechanical energy dissipation of the pump under cavitation conditions, accounting for more than 50%. NPSH has significant effects on the cavitation pattern, which reflects on the field that the areas of attached sheet cavitation and tip leakage vortex cavitation around blades increase obviously with NPSH reducing under the tip clearance of 0.1% span. With NPSH decreasing, high regions of turbulent dissipation in the impeller mainly expands along blades and move downstream, with span S0.98 near the shroud having larger turbulent dissipation. Besides, high regions of turbulent dissipation are mainly distributed at the rear part of the cavity for every corresponding span of the impeller, which indicates that the turbulent dissipation has a strong relation with the cavitation pattern. In the impeller, the unstable flows cause cavity shedding at the rear of the cavity and wake flows near the blade trail induce higher turbulent kinetic energy, finally resulting in higher turbulent dissipation there. Under the same NPSH, areas of tip leakage vortex cavitation and areas of tip clearance cavitation around the tip both expand with the tip clearance increasing from 0.1% span to 0.8% span. And high areas of turbulent dissipation also are distributed at the rear of the cavity and moving downstream along the blade suction side, especially at span S0.98. Therefore, the tip clearance width mainly affects the cavitation development and turbulent dissipation distribution near the impeller’s shroud under same NPSH.
A Case Study of an Optimal Detailed Analysis of a Standalone Photovoltaic/Battery System for Electricity Supply in Rural and Remote Areas
Authors: Zieba Falama Ruben , Yaouba  , Menga Francis-Daniel , Hamda Soulouknga Marcel , Kwefeu Mbakop Fabrice , Ben Salah Chokri
Published: June 2022

This paper focused on a techno-economic study of a standalone PV/battery system for electrical energy supply. For a particular case study in Cameroon, the system is optimally designed thanks to a double-objective firefly optimization algorithm, based on a defined operational strategy. The two objective functions simulated simultaneously using FA are: the cost of energy (COE) function and the function defining the loss of power supply probability (LPSP). Different optimal configurations of the system have been obtained on the Pareto front with respect to their LPSP. For a total load demand of 20196.7 kWh, the lowest cost configuration with LPSP of 0% is composed by a number of 63 modules and a battery capacity of 370.295 kWh. The related COE is 0.2587 $/kWh, corresponding to a total net present cost of 87422 $. However with this configuration, the energy of batteries could not be able solely to respond to the energy demand for 3 continuous days. In that case, the increase of the PV power production (by increasing the number of PV modules) could allow to the batteries to fulfil this deficiency. But this solution increases the investment cost to up to 11.17%, considering a system with 80 PV modules. Another solution consists in reducing the size of the battery bank to avoid its unnecessary oversizing. In this case, the COE and the system investment cost reduce to up to 28.77% for 1 day batteries’ autonomy considered. The obtained results have demonstrated that the cost of a PV/battery system is mostly influenced by the batteries’ size, while the system reliability is mostly related to the PV size.
Review of Clay-Based Nanocomposites as Adsorbents for the Removal of Heavy Metals
Authors: Kinoti Ismael Kithinji , Karanja Esther Muthoni , Nthiga Esther Wanja , M’thiruaine Cyprian Muturia , Marangu Joseph Mwiti
Published: June 2022

Due to rapid industrialization, urbanization, and surge in modern human activities, water contamination is a major threat to humanity globally. Contaminants ranging from organic compounds, dyes, to inorganic heavy metals have been of major concern in recent years. This necessitates the development of affordable water remediation technologies to improve water quality. There is a growing interest in nanotechnology recently because of its application in eco-friendly, cost-effective, and durable material production. This study presents a review of recent nanocomposite technologies based on clay, applied in the removal of heavy metals from wastewater, and highlights the shortcomings of existing methods. Recently published reports, articles, and papers on clay-based nanocomposites for the removal of heavy metals have been reviewed. Currently, the most common methods utilized in the removal of heavy metals are reverse osmosis, electrodialysis, ion exchange, and activated carbon. These methods, however, suffer major shortcomings such as inefficiency when trace amounts of contaminant are involved, uneconomical costs of operation and maintenance, and production of contaminated sludge. The abundance of clay on the Earth’s surface and the ease of modification to improve adsorption capabilities have made it a viable candidate for the synthesis of nanocomposites. Organoclay nanocomposites such as polyacrylamide-bentonite, polyaniline-montmorillonite, and β-cyclodextrin-bentonite have been synthesized for the selective removal of various heavy metals such as Cu2+, Co2+, among others. Bacterial clay nanocomposites such as E. coli kaolinite nanocomposites have also been successfully synthesized and applied in the removal of heavy metals. Low-cost nanocomposites of clay using biopolymers like chitosan and cellulose are especially in demand due to the cumulative abundance of these materials in the environment. A comparative analysis of different synthetic processes to efficiently remove heavy metal contaminants with clay-based nanocomposite adsorbents is made.
Application of Data Mining Technology in Enterprise Digital Human Resource Management
Authors: Zhou Da
Published: June 2022

The purpose of this paper is to explore the practical application of big data comprehensive mining and analysis technology in the overall human resource management work of the entire enterprise under the gradual increase in the amount of enterprise data, so as to effectively improve the overall core strategic competitiveness of the entire enterprise and improve the overall human resource management level of the entire enterprise. This article adopts the risk management theory of quantifying the characteristics of business management data, analyzes various management models in modern human resource information system management, and analyzes the entire process of modern enterprise daily operation and various types of human resource system risk management and business data. Combined with quantitative management theory, it introduces the basic concepts of business data feature mining system theory and its most common six data analysis and calculation methods. The module design examples are organically combined, and the traditional data mining analysis theory and its application are extended to the enterprise human resource project management information system. Finally, the experimental results show that the use of big data mining and analysis technology can solve the problems of human resource quality management in small- and medium-sized enterprises. The independent quantitative data mining analysis model has achieved 25% improvement in the application effect of the analysis of the types of human resources in management enterprises, the prevention of internal talent loss in management enterprises, and the performance evaluation management system of enterprises.
Micro‐ and Nanostructure of Layered Si\Sn\Si Films, Formed by Vapor Deposition
Authors: Neimash V. B. , Shepelyavyi P. Ye. , Nikolenko A. S. , Strelchuk V. V. , Chegel V. I.
Published: June 2022

The peculiarities of surface relief of the Si‐Sn‐Si layered films, used to produce the silicon nanocrystals with properties of quantum dots, were studied by the methods of electron and atomic force microscopy with the involvement of X‐ray fluorescent microanalysis. It was shown that the quasispherical structuring of the relief at the scale 20‐20000 nm is typical for the surface of silicon‐tin layered films. The role of layer thicknesses is experimentally analyzed under formation of the surface relief (roughness, shapes, and lateral dimensions) during their vacuum deposition from a vapor‐gas phase. The peculiarities of the relief of amorphous silicon films deposited on the surface of molten tin are shown. The fractal‐like type nanostructuring of amorphous silicon films deposited on the surface of liquid tin was discovered.
Rivea hypocrateriformis (Desr.) Choisy: An Overview of Its Ethnomedicinal Uses, Phytochemistry, and Biological Activities and Prospective Research Directions
Authors: Mukim Mohammad , Kabra Atul , Hano Christophe , Drouet Samantha , Tungmunnithum Duangjai , Chaturvedi Mohit , Patel Rakesh , Ayaz Muhammad , Shadrack Daniel M.
Published: June 2022

Rivea hypocrateriformis (Desr.) Choisy is a robust woody climbing shrub of the genus Rivea which is widely distributed in India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar, and Thailand. R. hypocrateriformis is a promising medicinal herb with a wide range of beneficial and health-promoting properties. Since the ancient times, it has been used as a traditional medicine to treat rheumatic pain, fever, urogenital problems, snake bites, cough, piles, malaria, and skin diseases. Aside from these traditional uses, its leaves and young shoots are also cooked and eaten as a vegetable and used for the preparation of bread with millet flour. This study extensively analyzes the available information on R. hypocrateriformis botanical characterization, distribution, traditional applications, phytochemistry, pharmacology, and toxicological properties. Phytochemical investigations of the plant has revealed the presence of highly valuable secondary metabolites including alkaloids, glycosides, coumarins, flavonoids, xanthones, stilbenes, and other organic compounds. Its crude extracts and isolated compounds have revealed anovulatory, antifertility, antiarthritic, antimicrobial, anticancer, antioxidant hepatoprotective, antilithiatic, and antimitotic potentials. This review of literature clearly identifies R. hypocrateriformis as a potent medicinal plant with remarkable healing and health-promoting properties. Further research directions into the bioactive extracts, clinical, and toxicological evaluations to assess the beneficial health-promoting properties of this promising herb are also discussed.
[Retracted] Using Haemocoagulase Agkistrodon in Patients Undergoing Transurethral Plasmakinetic Resection of the Prostate: A Pilot, Real‐World, and Propensity Score‐Matched Study
Authors: Zhu Cong , Yang Lan , Zi Hao , Li Bing-Hui , Huang Qiao , Lu Meng-Xin , Li Xiao-Dong , Ren Xuan-Yi , Tao Hua , Hu Hankun , Zeng Xian-Tao
Published: June 2022

Objectives. To compare the clinical outcomes of using different hemostatic agents after transurethral plasmakinetic resection of the prostate (TUPKP) in benign prostatic hyperplasia (BPH) patients. Methods. The patients were divided into 5 groups according to the hemostatic agents used after TUPKP, including the haemocoagulase agkistrodon for injection (HCA), hemocoagulase for injection (HC), hemocoagulase bothrops atrox for injection (HCB), ethylenediamine diaceturate injection (EDD), and tranexamic acid (TXA). Propensity score matching was performed based on age, body mass index, prostate volume, hypertension status, fasting blood glucose, smoking, and drinking history. The hospitalization time, bladder irrigation time, indwelling catheterization time, the patency of urine flow, and blood transfusion records were used as outcome indicators to compare the clinical effects of these five agents. Results. We finally matched 65 pairs receiving HCA or HC, 71 pairs receiving HCA or HCB, 38 pairs receiving HCA or TXA, and 29 pairs receiving HCA or EDD. Compared with HC, HCA given during the perioperative period significantly reduced the median hospitalization time [7.00 days (5.00, 8.00) vs. 9.00 days (8.00, 10.00); p < 0.001] and median catheterization time (109.00 hours [88.00, 129.00] vs. 164.00 hours [114.00, 189.00], p < 0.001). Compared with EDD, the median hospitalization time (7.00 days [6.00, 8.00] vs. 10.00 days [8.00, 11.00]; p < 0.001) and median catheterization time (113.00 hours [95.00, 143.00] vs. 160.00 hours [139.00, 168.00]; p < 0.001) were also significant shorter in HCA group. Compared with HCB, median bladder irrigation time (45.00 hours [27.00, 71.00] vs. 49.00 hours [45.00, 72.00]; p = 0.04) was shorter in the HCA group. However, there were no statistical differences in outcomes between HCA and TXA. Conclusions. HCA probably has an advantage over HC, HCB, and EDD in reducing the hospitalization time, catheterization time, and bladder irrigation time among BPH patients undergoing TUPKP.
Analysis of the Correlation between Nutritional Status and Quality of Life of Patients with Gynaecological Ovarian Cancer during Postoperative Chemotherapy
Authors: Shi Xiaoming , Lv Yuchun , Wang Peiqi , Yang Xin , You Shengjun
Published: June 2022

Ovarian cancer mortality is on the rise in China. Surgery followed by adjuvant chemotherapy is the most extensively used treatment for tumour recovery. An excellent nutritional condition prior and throughout treatment serves to improve the quality of life and, as a result, the treatment result. The goal of this research was how diet affected the functioning standard of those living in carcinoma who were receiving postoperative treatment. BMI was utilised to evaluate nutrition, accompanied by albuminemia, prealbuminemia, and serum C-reactive protein, that is used to evaluate excessive catabolism. The QLQ-C30 questionnaire assessed standard of living. The performance status of the patient is decided with the help of the WHO performance scale for cancer patients. The study identified the statistically significant relationship between the performance status and hypercatabolism in the global health (quality of life) of the patient. While body mass index is often considered as a standard for assessment of nutritional status, it has affected only the cognitive function of the patient. In this study, we have concluded that in addition to direct measurement of the BMI, other clinical parameters such as serum CRP should be considered to get a better outcome of chemotherapy.
Abstract A12: Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma
Authors: Roszik Jason , Gombos Dan , Upshaw Joshua , Sarli Vanessa , Meas Salyna , Lucci Anthony , Hall Carolyn , Patel Sapna , Anand Kartik
Published: June 2022

Introduction: Uveal melanoma (UM) is a rare melanoma; only 5% of cases at initial presentation have distant metastasis. As approximately 50% of patients will develop metastatic disease, there is a need to detect minimal residual disease (MRD). Liquid biopsy using circulating tumor cells (CTCs) has been evaluated in multiple tumors; high CTC count predicts for increased risk of metastasis. We conducted a pilot study to check feasibility of CTCs in UM and evaluate if CTCs vary with risk status in early-stage UM.

Methods: We enrolled 40 UM patients ≥18 years, after obtaining informed consent in an IRB-approved protocol from 12/1/2014 to 2/1/2018. Peripheral blood was obtained to detect CTCs using CellSearch Circulating Melanoma Cell Assay. Demographic information, mutational analysis, date of diagnosis of primary UM or metastasis, and dates of CTC collection were collected. Risk stratification was done by gene expression profiling (GEP) by DecisionDX-UM assay. Landmark overall survival (OS) was calculated using “Landest” R package comparing CTC detected vs. not detected in early-stage UM.

Results: 39 patients were available for analysis. Median age of whole cohort was 52 years (20-83 years), 100% were non-Hispanic Caucasians, and 44% were male and 56% female. 20 patients had early-stage vs. 19 patients had metastatic disease at enrollment. 87% (13/15) of early-stage disease had class II disease. GNAQ & GNA11 mutations were present in 36% (12/39) and 13% (5/29), respectively. At initial blood draw, 36% of the patients had detectable CTCs [30% (6/20) in early stage vs. 42% (8/19) in metastatic], which increased to 54% at median study follow-up of 16.4 months [40% (8/20) in early stage vs. 68% (13/19) in metastatic]. Mean CTCs were higher in metastatic (9) vs. early stage (1.83) (p>0.05). 5 patients in early-stage disease developed distant metastasis; 60% (3/5) had detectable CTCs before radiographic detection of metastasis. Out 5, 80% had class II disease and 20% had unknown GEP. Landmark overall survival (from study enrollment) at 24 months was statistically worse in CTC detected vs. not detected in early-stage UM (P<0.05).

Conclusion: CTCs are more frequently detected in metastatic compared to early-stage UM. In early-stage UM, presence of CTCs predicts for increased risk of metastatic disease and is associated with worse outcome.

Citation Format: Jason Roszik, Dan Gombos, Joshua Upshaw, Vanessa Sarli, Salyna Meas, Anthony Lucci, Carolyn Hall, Sapna Patel, Kartik Anand. Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A12.
Abstract B19: Suppression of CD8+ T-cell functions by melanoma cell-derived exosomes captured from plasma of patients with melanoma
Authors: Sharma Priyanka , Diergaarde Brenda , Ferrone Soldano , Kirkwood John M , Whiteside Theresa L.
Published: June 2022

Exosomes, virus-sized (30-150nm) vesicles, derived from the endocytic compartment of parent cells, are produced by all cells and are present in all body fluids. Melanoma patients’ plasma contains exosomes produced by normal and malignant cells. To study the impact of melanoma cell-derived exosomes (MTEX) on human immune cells and melanoma progression, we isolated MTEX from total exosomes in plasma by immune capture with anti-CSPG-4 mAbs on beads. 19 proteins carried by MTEX and by non-MTEX of 12 patients with metastatic melanoma were quantified by on-bead flowcytometry. Immunoregulatory functions of these exosomes were measured in co-incubation assays with human immune cell subsets. Plasma exosomes of 6 normal donors served as controls. Melanoma-associated antigens (MAA) were present on MTEX only. MTEX carried more inhibitory ligands than non-MTEX (FasL, p<0.007; TRAIL, p<0.02), inhibited CD69 expression (p<0.002) on CD8+ T cells, suppressed T-cell proliferation (p<0.0005), and induced apoptosis of CD8+ T cells (p< 0.0005). MTEX-mediated suppression accounted for suppressive activities of total plasma exosomes. Although non-MTEX were enriched in immunostimulatory proteins (p<0.002), they induced greater suppression of NKG2D on NK cells than MTEX (p<0.001). This is the first study to show that MTEX, a subset of circulating exosomes derived from melanoma cells, are largely responsible for immuno-suppressive effects that potentially translate into systemic immune suppression and tumor promotion in melanoma patients.

Citation Format: Priyanka Sharma, Brenda Diergaarde, Soldano Ferrone, John M Kirkwood, Theresa L. Whiteside. Suppression of CD8+ T-cell functions by melanoma cell-derived exosomes captured from plasma of patients with melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B19.
Abstract IA12: Preventing melanoma progression through a genomic approach
Authors: Berwick Marianne ,   InterMEL
Published: June 2022

The InterMEL Program Project has been designed to fill a gap in our knowledge about the biology and clinical course of Stage II and Stage III melanoma. This program, Integration of Clinical and Molecular Biomarkers for Melanoma Survival, is work from a consortium of 12 institutions, using primary melanomas, and differs from the TCGA, which was 80% metastatic melanoma. We are attempting to use genomics (next-gen sequencing, methylation analyses, miRNA, and expression analyses) to form an integrated signature for survival among those diagnosed with Stages II and III melanoma. Such a signature could assist clinicians in determining whether to treat the patient, prior to metastases, with newer therapies or to less aggressively follow those patients unlikely to die of their disease. To do this, we are evaluating 1,000 tumors—500 from those who died from melanoma within 5 years, and 500 from those who lived more than 5 years without progression. Expert pathologists review each lesion for eligibility and classification of clinical characteristics. These tumors have not been treated with immunotherapy or targeted therapies. Full clinical information is available for each tumor, including age, sex, race/ethnicity, anatomic site, histologic subtype, AJCC8 stage, sentinel lymph node status, Breslow thickness, ulceration, mitotic index, TILs, regression, satellites, tumor purity, date of progression (if progressed), vital status, follow-up time to death or last contact. To date, we have clinical and pathologic data on more than 500 of the 1,000 tumors and genomic data on more than 100 of these. We find better survival among those with higher mutation burden, poorer survival among those with a CIMP methylation phenotype, and a number of miRNAs associated with survival.

Citation Format: Marianne Berwick, InterMEL. Preventing melanoma progression through a genomic approach [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr IA12.
Abstract PR06: The glutaminase inhibitor CB-839 potentiates antimelanoma activity of standard-of-care targeted therapies and immunotherapies
Authors: Varghese Sruthy , Pramanik Snigdha , Prasad Rishika , Hodges Hannah , Williams Leila , Peng Weiyi , Tawbi Hussein , Nanda Vashisht Yennu
Published: June 2022

Nearly all metastatic melanoma patients who respond to targeted therapies will relapse with the disease within a year. Although more durable responses are seen with immune therapies, about half of the melanoma patients do not respond to them, and a significant number of responders eventually relapse. Most relapsed melanomas also exhibit post-treatment resistance to these treatments. Hence, there is a clear and present need to develop therapeutics that counteract resistance associated with relapse. We and others earlier showed that melanomas with elevated mitochondrial activity possess improved cellular rigor and are intrinsically resistant to the antitumor effects of BRAF and MEK inhibitors. In many other instances, melanomas that initially respond to these inhibitors acquire resistance by elevating mitochondrial activity. Mitochondrial activity is elevated in part by increased cellular uptake of glutamine, and its conversion to alpha-ketoglutarate in the TCA cycle, with glutaminase enzyme playing a rate-limiting role. In this study, we show that BRAFV600E-mutant melanomas with intrinsic or acquired resistance to MAPK pathway inhibitors have lower glucose uptake and increased glutamine uptake compared to those that are sensitive. Treatment of these resistant melanomas with single-agent glutaminase inhibitor, CB-839, moderately inhibited their growth. However, a more robust inhibition of their growth was achieved when CB-839 was combined with BRAF and MEK inhibitors. In addition, CB-839 increased the in vivo activity of tumor-infiltrating lymphocytes (TILs) in a mouse vaccine model and also enhanced the proapoptotic effect of human autologous patient-derived TILs on their cognate melanoma cells. Seahorse bioenergetics stress tests showed that CB-839 inhibited mitochondrial OxPhos in tumor cells to a greater extent than in activated TILs. Additional molecular studies are currently in progress. A recent clinical trial in melanoma patients showed that combination treatment with CB-839 and the immune checkpoint blocker, nivolumab, caused an objective response in three melanoma patients who had earlier progressed on treatment with immune checkpoint blockade. Our preclinical results complement this clinical finding and suggest that CB-839 combination could potentiate the efficacy of targeted and immune therapies in refractory melanomas.

Citation Format: Sruthy Varghese, Snigdha Pramanik, Rishika Prasad, Hannah Hodges, Leila Williams, Weiyi Peng, Hussein Tawbi, Vashisht Yennu Nanda. The glutaminase inhibitor CB-839 potentiates antimelanoma activity of standard-of-care targeted therapies and immunotherapies [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr PR06.
Behandlung der chronischen Bronchusstumpfinsuffizienz bei inoperablen Patienten
Authors: Hekmat Khosro
Published: June 2022

Hintergrund: Bronchopleurale Fisteln sind eine relativ seltene Komplikation nach einer Lungenresektion. Bei inoperablen Patienten sind verschiedene endoskopische Verfahren zur Behandlung beschrieben worden. Wenn die bronchopleuralen Fisteln groß und chronisch sind, machen die persistierenden Luftleckagen eine operative Behandlung erforderlich, während ein endoskopischer Atemwegsstent eine hilfreiche palliative Behandlung darstellt. Ziel: Wir beschreiben den erfolgreichen Verschluss einer großen, chronischen bronchopleuralen Fistel mit einem expandierbaren Polyvinylalkohol (PVA)-Schwamm und Cyanoacrylat-Klebstoff. Methoden: Bei allen Patienten wurde mit einem starren Bronchoskop ein kleiner Zylinder aus PVA-Schwammmaterial in die Fistel eingebracht. Nach Platzierung des Patchs wurde mit einem Lumenkatheter Cyanoacrylat-Klebstoff unmittelbar auf den PVA-Schwamm aufgebracht. Dadurch dehnte sich das Gerinnsel, und die Luftleckage wurde verschlossen. Das langfristige Behandlungsergebnis wurde mittels flexibler Bronchoskopie 3 Monate lang monatlich und danach alle 6 Monate bis 5 Jahre nach dem Eingriff kontrolliert. Ergebnisse: Wir behandelten endoskopisch 7 konsekutive Patienten mit bronchopleuralen Fisteln von 4-8 mm Durchmesser. Bei 6 der 7 Patienten war die Fistel am Bronchusstumpf lokalisiert. Beim 7. Patienten wurde die Fistel an der rechten Wand der distalen Trachea visualisiert. Ein temporärer Fistelverschluss wurde bei allen 7 Patienten erreicht, ein definitives Ergebnis bei 5 der 7 Patienten. Schlussfolgerungen: Die Anwendung eines expandierbaren PVA-Schwamms in Verbindung mit Cyanoacrylat-Kleber ist eine mögliche Strategie für den endobronchialen Verschluss einer bronchopleuralen Fistel.
Prolaktin als prädiktiver Marker bei Therapie des NSCLC mit Nivolumab
Authors: Schumann Christian
Published: June 2022

Hintergrund/Ziele: Prolaktin (PRL) ist ein Peptidhormon, dem mehrere Studien eine Rolle als Zytokin im Rahmen der durch T-Zellen vermittelten Immunität beim Menschen bescheinigen. Wir wissen nicht, ob PRL ein positiver oder negativer Immunmodulator ist, doch seine Auswirkungen auf die Regulation der T-Zellen könnten die antitumorale Aktivität von Nivolumab (NIVO) beeinträchtigen. Unser Ziel war es zu untersuchen, ob das Vorliegen von Hyperprolaktinämie bei Patienten mit metastasiertem nicht-kleinzelligen Lungenkarzinom (mNSCLC), die mit NIVO behandelt wurden, mit einem schlechteren klinischen Verlauf assoziiert war. Methoden: Wir evaluierten 26 mNSCLC-Patienten, die mit NIVO behandelt wurden. Jedem Patienten wurden Blutproben entnommen, um den PRL-Ausgangswert vor Beginn der NIVO-Therapie sowie vor jeder folgenden NIVO-Gabe zu messen. Alle Patienten unterzogen sich einer konventionellen CT-Untersuchung zur Beurteilung des Therapieeffekts laut IrRECIST-Kriterien (Immune-related Response Evaluation Criteria in Solid Tumors). Ergebnisse: Bei 20 Patienten (77%) trat unter der Therapie Hyperprolaktinämie auf, bei 6 Patienten (23%) blieb der PRL-Wert während der Therapie stabil (p = 0,001). Insgesamt erlitten 95% der 20 Patienten mit Hyperprolaktinämie eine Krankheitsprogression laut CT-Bildgebung, von den 6 Patienten mit stabilem PRL-Wert hingegen trat nur bei 2 (33%) eine Progression ein (p = 0,004). Schlussfolgerungen: Hyperprolaktinämie bei mNSCLC-Patienten unter NIVO-Therapie könnte potenziell ein negativer früher prädiktiver Faktor für einen schlechten Verlauf sein, wie er später als Progression im CT erkennbar wird.
Switch from Hemodialysis to Peritoneal Dialysis: Does the Time Spent on Hemodialysis Impact Outcomes in Peritoneal Dialysis?
Authors: Legendre Bruno , Lobbedez Thierry , Couchoud Cécile , Lassalle Mathilde , Kazes Isabelle , Lanot Antoine , Boyer Annabel , Béchade Clémence
Published: June 2022

Introduction: Switch from hemodialysis (HD) to peritoneal dialysis (PD) is unfrequent, but incentive strategies to perform PD can lead to an increase of these transitions. However, data on transitioning from HD to PD are scarce. We hypothesized that time spent on HD before transfer to PD would impact PD outcomes. Methods: This registry-based, nationwide study analyzed patients transferred from HD to PD. Patients who began HD between January 2008 and December 2016 were included. Cox and Fine and Gray regression models were used to explore the relationship between time spent on HD before PD and outcomes in PD: PD cessation for death or retransfer to HD (composite endpoint); for death; and for retransfer to HD. Results: Over the study period, 1,985 of the 77,587 HD starters (3%) were transferred to PD. The median time spent on HD before transfer to PD was 1.94 months (interquartile range [IQR] 1.02–4.01). The median survival time on PD after this transition was 20 months (IQR 18–21). Time spent on HD before PD was associated with increased risk of death or retransfer to HD (cause-specific hazard ratio [cs-HR] 1.01, 95% confidence interval [CI]: 1–1.02 for a 1-month increase) and death (cs-HR 1.02, 95% CI: 1.01–1.03) but not with retransfer to HD censored on death (cs-HR 1.00, 95% CI: 0.99–1.01). The results were similar when considering competing events. Discussion/Conclusion: Switch from HD to PD is rare in France. Time spent on HD before transfer is associated with patient survival but not with retransfer to HD.
NMT1 Enhances the Stemness of NSCLC Cells by Activating the PI3K/AKT Pathway
Authors: Zou Wailong , Zhang Xinjun , Wang Yumin , Yan Lei , Wu Xiaorui , Yang Rui , Li Yulin , Zhang Jia , Chen Jichao
Published: June 2022

Introduction: Abundant studies have disclosed that proteins can function as pivotal tumor promoters or suppressors in cancers’ progression. This work was planned to investigate the regulatory function of N-myristoyltransferase-1 (NMT1) on non-small cell lung cancer (NSCLC) and the underlying molecular mechanisms. Methods: The self-renewal abilities were assessed through a spheroid-formation assay. The tumorigenic abilities were examined through nude mice in vivo assay. The proteins’ expression was measured through Western blot. The NMT1 protein expression in tumor tissues was measured through an IHC assay. The cell migration and invasion was confirmed through a transwell assay. The IC50 was verified through a CCK-8 assay. The NMT1 mRNA expression in NSCLC tissues was detected through RT-qPCR. Results: It was demonstrated that NMT1 exhibited higher expression in spheroid cells. Additionally, NMT1 facilitated the stemness in NSCLC. It was also found that NMT1 accelerated NSCLC tumor metastasis and the resistance to cisplatin. Moreover, NMT1 activated the PI3K/AKT pathway to facilitate stemness in NSCLC. NMT1 was also higher in tumor tissues of NSCLC patients and resulted in a poor survival rate. Conclusion: NMT1 enhanced the stemness of NSCLC cells by activating the PI3K/AKT pathway. This discovery suggested that NMT1 may be a valid therapeutic biomarker for NSCLC.
Gluten-Free Diet in Childhood Difficult-to-Treat Nephrotic Syndrome: A Pilot Feasibility Study
Authors: Srivastava Tarak , Dell Katherine M. , Lemley Kevin V. , Gipson Debbie S. , Kaskel Frederick J. , Meyers Kevin Edward , Faul Christian , Goldhaber Ayelet , Pehrson LauraJane , Trachtman Howard
Published: June 2022

Introduction: Minimal change disease in childhood can follow a frequently relapsing or steroid-dependent course in up to 40% of cases. Second-line immunosuppressive medications that are used to manage these patients are associated with significant adverse effects. There is a need for safer alternative treatments for difficult-to-treat nephrotic syndrome. Therefore, we conducted an open-label feasibility study to assess the safety and efficacy of a gluten-free diet as treatment for pediatric patients with difficult-to-treat nephrotic syndrome. As a second aim, we sought to determine if the plasma zonulin concentration can identify those who are more likely to respond to this intervention. Methods: Seventeen patients were placed on a gluten-free diet for 6 months. A positive response was defined as a 50% reduction in the relapse rate compared to the preceding 6 months or the ability to discontinue 1 immunosuppressive drug. Results: Five (29%) participants had a positive response to the dietary intervention. The gluten-free diet was well tolerated with no clinical or laboratory adverse events. Plasma zonulin concentration was elevated in patients who failed to benefit from the gluten-free diet. Discussion/Conclusion: A gluten-free diet may be a useful adjunctive intervention for patients with difficult-to-treat nephrotic syndrome that can be implemented prior to resorting to second-line immunosuppressive therapy. Development of the plasma zonulin level as a biomarker to predict efficacy would facilitate rational use of a gluten-free diet in the management of nephrotic syndrome.
The Open Field Test as a Tool for Behaviour Analysis in Pigs: Recommendations for Set-Up Standardization – A Systematic Review
Authors: Schulz Mareike , Zieglowski Leonie , Kopaczka Marcin , Tolba René H.
Published: June 2022

Introduction: The open field test (OFT) is a common tool to assess anxiety and behavioural changes in rodents. It has been adapted to pigs with no systematic investigation of how environmental changes may alter the performance of pigs. Currently, the number of published studies including the OFT in domestic pig models is increasing without standardization. Methods: Our review aimed to investigate the open field (OF) set-ups in published studies and the similarities between performance and published parameters. Results: Following the PRISMA guidelines for reviews, we selected 69 studies for inclusion in this systematic review. We determined the specific set-up conditions such as dimensions, duration, and time of day for most of the included studies; we found high variability across studies with respect to these test specifics. Discussion: Our results indicate the inconsistent implementation of the set-up, including dimensions, timing, parameters, and additional combined tests (e.g., new object tests). Based on our findings, we have made recommendations for the performance of the OFT, according to the current literature.
Estrogen Receptor-β Agonists Modulate T-Lymphocyte Activation and Ameliorate Left Ventricular Remodeling During Chronic Heart Failure
Authors: Rosenzweig Rachel , Kumar Vinay , Gupta Sahil , Bermeo-Blanco Oscar , Stratton Matthew S. , Gumina Richard J. , Bansal Shyam S.
Published: June 2022

Background:

CD4
+
T cells temporally transition from protective to pathological during ischemic heart failure (HF; 8 weeks postmyocardial infarction). Cellular mechanisms mediating this shift are unknown.

Methods:

RNA-sequencing of cardiac CD4
+
T cells and flow cytometric analysis of immune cells was conducted.

Results:

RNA-sequencing of CD4
+
T cells from the failing hearts of male mice indicated activation of ER (estrogen receptor)-α signaling. Flow cytometric analysis showed that ERα in CD4
+
T cells decreases significantly at 3-day postmyocardial infarction but increases during HF. To antagonize ERα, we tested a novel ERβ agonist (OSU-ERb-012) to inhibit T cells and blunt left ventricular remodeling. Proliferation assays showed that OSU-ERb-012 dose-dependently inhibited proliferation and proinflammatory cytokine expression in anti-CD3/CD28 stimulated splenic T cells isolated from both the sexes. For in vivo efficacy, 10- to 12-week-old male and ovariectomized female mice were randomized at 4 weeks postmyocardial infarction and treated with either vehicle or drug (60 mg/kg per day; oral). While vehicle-treated HF mice displayed progressive left ventricular dilatation with significantly increased end-systolic and end-diastolic volumes from 4 to 8 weeks postmyocardial infarction, treatment with OSU-ERb-012 significantly blunted these changes and stopped left ventricular remodeling in both the sexes. Reduction in tibia-normalized heart and left ventricular weights, cardiomyocyte hypertrophy and interstitial fibrosis further supported these results. Additionally, OSU-ERb-012 treatment selectively inhibited cardiac, splenic, and circulating CD4
+
T cells without affecting other myeloid and lymphoid cells in the HF mice.

Conclusions:

Our studies indicate that ERβ agonists and OSU-ERb-012, in particular, could be used as selective immunomodulatory drugs to inhibit CD4
+
T cells during chronic HF.
Genetically‐Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage
Authors: Szejko Natalia , Acosta Julian N. , Both Cameron P. , Leasure Audrey , Matouk Charles , Sansing Lauren , Gill Thomas M. , Hongyu Zhao , Sheth Kevin , Falcone Guido J.
Published: June 2022

Background

The evidence linking vitamin D (VitD) levels and spontaneous intracerebral hemorrhage (ICH) remains inconclusive. We tested the hypothesis that lower genetically determined VitD levels are associated with higher risk of ICH.

Methods and Results

We conducted a 2 sample Mendelian Randomization (MR) study using publicly available summary statistics from published genome‐wide association studies of VitD levels (417 580 study participants) and ICH (1545 ICH cases and 1481 matched controls). We used the inverse‐variance weighted approach to generate causal estimates and the MR Pleiotropy Residual Sum and Outlier and MR‐Egger approaches to assess for horizontal pleiotropy. To account for known differences in their underlying mechanism, we implemented stratified analysis based on the location of the hemorrhage within the brain (lobar or nonlobar). Our primary analysis indicated that each SD decrease in genetically instrumented VitD levels was associated with a 60% increased risk of ICH (odds ratio [OR], 1.60; [95% CI, 1.05–2.43];
P
=0.029). We found no evidence of horizontal pleiotropy (MR‐Egger intercept and MR Pleiotropy Residual Sum and Outlier global test with
P
>0.05). Stratified analyses indicated that the association was stronger for nonlobar ICH (OR, 1.87; [95% CI, 1.18–2.97];
P
=0.007) compared with lobar ICH (OR, 1.43; [95% CI, 0.86–2.38];
P
=0.17).

Conclusions

Lower levels of genetically proxied VitD levels are associated with higher ICH risk. These results provide evidence for a causal role of VitD metabolism in ICH.