bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency Measurement of Urban and Rural Logistics Supply Chain System Based on Fuzzy Algorithm
Authors: Qiao Pengliang
Published: April 2022

At this stage, China’s logistics industry is developing rapidly and has become one of the important areas of China’s economic development. However, there are few techniques for measuring the efficiency of logistics supply chain systems. In order to be able to effectively analyze the efficiency measurement of the urban and rural logistics supply chain system and obtain higher accuracy, using a method derived from analysis of data envelopes, this essay examines the impact elements by establishing a data envelopment analysis model, using compound DEA analysis method and linear regression analysis method. The composite DEA analysis shows that all indicators in the indicator system are positively correlated, and the amount of people working in the field of distribution has the greatest impact on logistics efficiency. The annual average of pure technical efficiency is 0.932, and the annual average of scale efficiency is 0.910. In the eastern region, it is a lower-middle level. The empirical results of changes in the efficiency of the urban and rural logistics industry show that there is a significant positive correlation. This paper also builds a fuzzy algorithm optimization model and designs an overall fuzzy algorithm to solve the LRPPD problem. The simulation results show that the algorithm has good optimization performance, high computational efficiency, and strong convergence speed.
Enhanced Electrochemical Sensor for Electrocatalytic Glucose Analysis in Orange Juices and Milk by the Integration of the Electron-Withdrawing Substituents on Graphene/Glassy Carbon Electrode
Authors: Zainul Rahadian , Isa Illyas Md , Akmar Mohd Yazid Siti Nur , Hashim Norhayati , Mohd Sharif Sharifah Norain , Saidin Mohamad Idris , Ahmad Mohamad Syahrizal , Suyanta M.Si , Amir Yulkifli
Published: April 2022

In this work, a novel electrochemical sensor was developed by electron-withdrawing substituent modification of 1-phenyl-3-methyl-4-(4-fluorobenzoyl)-5-pyrazolone on a graphene-modified glassy carbon electrode (HPMpFP-graphene/GCE) for glucose detection. The results of characterizations using a scanning electron microscope, Fourier transform infrared spectroscopy, Raman spectroscopy, and nuclear magnetic resonance spectroscopy showed the successful fabrication of HPMpFP-graphene nanocomposite, which served as an electroactive probe for glucose detection. The electron transfer ability of HPMpFBP-graphene/GCE has been successfully revealed using cyclic voltammetry and electrochemical impedance spectroscopy results. The good electrochemical performance was shown by well-defined peak currents of square wave voltammetry under various parameters, including pH, HPMpFP and graphene composition, and scan rate effect. A high electrochemically evaluated surface area using chronoamperometry suggested that the present glucose detection response was intensified. The chronoamperometry results at a work potential of 0.4 V presented a wide linear range of 1 × 103–90 µM and 88–1 µM with 0.74 µM (S/N = 3) as the detection limit. An acceptable recovery has been revealed in the real sample analysis. The electrochemical sensing behaviour of the composite indicates that it may be a promising candidate for a glucose sensor and it significantly extends the range of applications in the electrochemical field.
Research on Mathematics Classroom Teaching Optimization Model Based on GA Neural Network
Authors: Zheng Yuhui
Published: April 2022

The teaching characteristic of colleges and universities is determined by the teaching quality of teachers, but it is difficult to calculate with a linear mathematical explanation how to judge the teaching quality of teachers. In most colleges and universities, expert evaluations, supervision groups, peers listening to lectures in the classroom, and students' after-class evaluations are still used to determine the teaching ability of professors. It is undeniable that these judgment methods have certain practicality. Especially for new teachers, experts and peers can find problems in time and help new teachers quickly correct them, and they can also know how to better practice the “student-centered” teaching concept from the feedback of students after class. However, these judgment standards also have their limitations. For example, the classroom quality judgment standards for experts and peers are mostly set by some administrative departments according to social requirements, leadership requirements, and subjective cognition. Various institutions should have different weights for the same criterion, and if they all employ the same criteria, it will easily lead to imprecise conclusions. In addition, the expert group and students are also subjective and incomplete in the stage of teacher evaluation. Based on different nonquantitative factors, the evaluation standards for teachers in colleges and universities also need the scientific theoretical basis. Therefore, many scientists are considering whether to use a more intelligent and reasonable way to judge the quality of teaching. Nowadays, with the popularization of artificial intelligence (AI), the use of neural networks (NNs) is becoming more and more comprehensive. According to the characteristics of NNs, this paper uses the GA NNs algorithm to signify that this algorithm can be effectively used in the evaluation of teachers' teaching quality. In this paper, a large number of experimental results show that the use of GA NNs can be used to evaluate the quality of teaching, and the evaluation results can be obtained quantitatively in this way. For the assessment of teaching quality, quantitative results are also more powerful in teaching evaluation.
BNT162b2 COVID-19 Vaccine Induced Immune Thrombocytopenic Purpura
Authors: Ghosh A. K. , Bhushan S. , Lopez L. D. R. , Sampat D. , Salah Z. , Hatoum C. A.
Published: April 2022

Immune thrombocytopenic purpura (ITP) has been reported following vaccinations such as MMR as well as after viral infections such as hepatitis C and HIV. Few case reports have been reported of ITP after COVID-19 infections and COVID-19 vaccines. Herein, we present a patient who presented with severe ITP with a platelet count of 0 after receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine (also known as the Pfizer BioNTech). She subsequently recovered with a prolonged treatment course.
The Impact of Microsoft Mathematics Visualization on Students Academic Skills
Authors: Rabi Fazli , Fengqi Ma , Aziz Muhammad , Ihsanullah Muhammad
Published: April 2022

The purpose of this study is to examine whether there is a relationship between academic skills and Microsoft Mathematics Visualization as a result of the use of Microsoft Mathematics Visualization in the classroom. Specifically, when it comes to academic skills, Microsoft Mathematics Visualization is considered an independent variable, and academic skills are considered a dependent variable that has been influenced by the negative or positive characteristics of various instructional methodologies. The quantitative research approach has been used in the development of this document. Approximately 300 responses were collected during data collection, and, following correction, the sample size was decreased to 268 responses, which were mined in SPSS to generate the results. In the findings of the model summary, it is shown that the selected model has a very good above-average value of adjusted R2, suggesting a good fit, in accordance with the results of model summary. Microsoft Mathematics Visualization is regarded to be a predictor for academic skills since its coefficient of 0.794 on conversion explains up to 79.4 percent of the variance of the model when converted. We have “B” = “0.892” as the value of the predictor’s beta in our first regression. For example, a one-unit change in Microsoft Mathematics Visualization will result in an 89.2 percent change in academics skills, which may be interpreted as follows: Aside from that, the correlation coefficient between Microsoft Mathematics Visualization and student caliber (r = 0.840) indicates a positive relationship between student caliber and Microsoft Mathematics Visualization. 0.963 indicates that formal schooling has been significantly influenced by Microsoft Mathematics Visualization training, which might be further elaborated as that formal education has been boosted by Microsoft visualization training, according to the results of the test.
Lupeol Stearate Accelerates Healing and Prevents Recurrence of Gastric Ulcer in Rodents
Authors: Somensi Lincon Bordignon , Costa Philipe , Boeing Thaise , Bolda Mariano Luísa Nathália , de Gregório Elizama , E Silva Aline Teixeira Maciel , Longo Bruna , Locatelli Claudriana , de Souza Priscila , Magalhães Cássia Gonçalves , Pains Duarte Lucienir , da Silva Luisa Mota
Published: April 2022

Objective. The focus of this study was to evaluate the gastric healing effect of lupeol stearate (LS) and its ability to minimize ulcer recurrence in rodents. Methods. To evaluate the gastric healing properties of LS, rats were subjected to 80% acetic acid-induced ulcer model and treated with vehicle, LS (1 mg/kg, p.o.), or omeprazole (20 mg/kg, p.o.), twice daily by seven days. The gastric ulcers were evaluated macroscopically, histologically, and biochemically. To evaluate the effects of LS in gastric ulcer recurrence, mice were ulcerated with 10% acetic acid and treated with vehicle, LS (1 mg/kg, p.o.), or ranitidine (100 mg/kg, p.o.), twice a day for ten days. Then, ulcer recurrence in these animals was induced by IL-1β at five days after the treatment period. Results. The oral treatment with LS accelerated gastric healing by 63% in rats compared to the vehicle group, evidenced by histological improvement and increased gastric mucin levels. Moreover, the gastric healing effects of LS in rats were accompanied by an elevation in glutathione S-transferase activity and a reduction in myeloperoxidase activity. Furthermore, the LS treatment reduced the recurred lesions in mice. Conclusions. The oral treatment of LS accelerates gastric healing in rats by favoring mucus production and reducing neutrophil migration, and it also can reduce ulcer recurrence. These data highlighted this compound as promising for developing new pharmacological strategies for the management of gastric ulcer.
Topical Application of Premna integrifolia Linn on Skin Wound Injury in Rats Accelerates the Wound Healing Process: Evidence from In Vitro and In Vivo Experimental Models
Authors: Alsareii Saeed Ali , Alzerwi Nasser A. N. , AlAsmari Mansour Yousef , Alamri Abdulrahman Manaa , Mahnashi Mater H. , Shaikh Ibrahim Ahmed
Published: April 2022

Background. When the skin and tissues within the body are injured, the healing process begins. Medicinal herbs have been used to cure wounds since time immemorial. The antimicrobial and antioxidant activity possessed by P. integrifolia may accelerate wound healing. Objectives. To assess the wound healing activity of Premna integrifolia extract (PIE) by employing in-vivo experimental animal models and an in-vitro migration scratch assay. Furthermore, to assess its cytotoxicity using the MTT assay. Methods. Wistar albino rats were used for the in vivo wound healing models. The animals were divided into four groups at random: Group I was untreated. Group II was vehicle control (ointment base). Group III was PIE ointment (5% W/W). Group IV was standard (povidone-iodine ointment) (5% W/W). The ointments were applied directly to the wounds as described above until they healed completely. The wound contraction percentage and tensile strength were calculated. The MTT test was used to determine the viability of the test extract against the fibroblast cells. The scratch assay was used in vitro to determine the wound healing potential of the test drug.

P
≤
0.05

values were considered statistically significant. Results. Premna integrifolia extract did not possess any noticeable cytotoxicity to the cell line and showed an IC50 of 185.98 μg/ml. The wound contraction potential of PIE ointment-treated animals was considerably greater (

P
≤
0.001

) on days 4, 8, 12, 16, and 20 when compared to the control group. The percentage of wound contraction on day 20 was 99.92% in PIE-treated animals compared to 83.23% in untreated animals. Compared to the untreated group, the duration of full epithelization was significantly (

P
≤
0.01

) shorter in the test group. When compared to the incision control group, the animals treated with PIE ointment had significantly higher (

P
≤
0.001

) tensile strength. In addition, animals given the test drug had a significant (

P
≤
0.001

) increase in total protein and hydroxyproline. In the in vitro scratch assay, test drug-treated cells demonstrated greater cell migration. Histology images confirmed that the test drug-treated group had epithelial tissue proliferation and keratinization. Conclusion. The current study found that Premna integrifolia improved wound healing activity both in vitro and in vivo. These findings indicate that Premna integrifolia extract has wound-healing potential and could be a viable source of nutraceuticals with wound-healing properties.
Vibegron for the Treatment of Patients with Dry and Wet Overactive Bladder: A Subgroup Analysis from the EMPOWUR Trial
Authors: Staskin David , Frankel Jeffrey , Varano Susann , Kennelly Michael , Newman Diane K. , Rosenberg Matt T. , Shortino Denise D. , Jankowich Rachael A. , Mudd Jr Paul N.
Published: April 2022

Background. Overactive bladder (OAB) is characterized by urgency and frequency with (OAB wet) or without (OAB dry) urge urinary incontinence (UUI). In the phase 3 EMPOWUR trial, vibegron—a selective β3-adrenergic receptor agonist for the treatment of OAB—significantly improved daily number of urgency episodes and micturitions vs. placebo (

P

 < 0.01). These post hoc analyses aimed to compare the efficacy of vibegron vs. placebo in OAB dry and wet populations. Methods. Patients were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, for 12 weeks. Baseline criteria for OAB dry included an average of ≥8 micturitions, ≥3 urgency episodes, and <1 UUI episode per diary day and for OAB wet included an average of ≥8 micturitions and ≥1 UUI episode per diary day. Change from baseline in mean daily number of urgency episodes and micturitions was assessed in both populations. Results. Of the 1463 patients included in the full analysis set, 336 (23%) had OAB dry (vibegron, N = 123; placebo, N = 115; and tolterodine, N = 98), and 1127 (77%) had OAB wet (vibegron, N = 403; placebo, N = 405; and tolterodine, N = 319). Vibegron was associated with significant reductions (95% CIs of the least squares mean differences [LSMD] does not include 0) from baseline at week 12 vs. placebo in mean daily urgency episodes for the dry (LSMD [95% CI], ‒1.0 [‒2.0, ‒0.1]) and wet (‒0.6 [‒1.0, ‒0.1]) populations. Vibegron was associated with significant reductions from baseline at week 12 vs. placebo in mean daily micturitions for the dry (LSMD [95% CI], ‒0.8 [‒1.5, ‒ 0.1]) and wet (‒0.5 [‒0.8, ‒0.1]) populations. There were no significant differences in either outcome between tolterodine and placebo for either the dry or wet populations in this study. Conclusions. In this subgroup analysis from the EMPOWUR trial, vibegron was associated with significant reductions compared with placebo in urgency episodes and micturitions in both the OAB dry and wet populations, suggesting that vibegron is similarly efficacious for these endpoints in patients with and without UUI. This trial is registered with NCT03492281.
Study on the Mechanism and Oxidative Stress of Compound Danshen on the Degradation of Cx43 and Improvement of Myocardial Apoptosis in ICM Rats
Authors: Chen XingHua , Zhang JiZhuo , Han Lu
Published: April 2022

In order to investigate the mechanism by which Salvia miltiorrhiza degrades connexin 43 (Cx43) and improves myocardial cell apoptosis and oxidative stress in rats with myocardial ischemia (ICM), male SD rats of pure grade are selected (32 rats), adaptively bred for 1 week, and then bred in SPF medium. They are randomly divided into a normal group, a model group, a low-dose Danshen group, and a high-dose group, with 8 rats in each group. HE staining and immunohistochemistry are performed. Serum samples are detected using kits according to instructions, including nitric oxide (NO) and endothelin-1 (ET-1); malondialdehyde (MDA), ELISA for superoxide dismutase (SOD), and vascular cell adhesion molecules (VCAM-1); western blot for detection of cardiac Cx43 protein expression; immunohistochemistry to detect Cx43 expression; and detection of myocardial ischemia. For ICM rats, the application of high-dose compound Salvia miltiorrhiza can effectively prevent the degradation of Cx43 protein, improve the apoptosis of myocardial cells in rats, and have a certain protective effect on ischemic myocardium in rats.
Immunohistochemistry Study of OY-TES-1 Location in Fetal and Adult Human Tissues
Authors: Fu Jun , Yingying Ge  , Qingmei Zhang  , Lin Yongda , Liu Chang , Nong Weixia , Luo Xin , Xiao Shaowen , Xie Xiaoxun , Luo Bin
Published: April 2022

OY-TES-1 is reportedly involved in carcinogenesis and spermatogenesis. However, the tissue distribution of OY-TES-1 in the normal human body remains elusive. This study detected OY-TES-1 expression in human fetal and adult normal tissues by immunohistochemistry. We identified a general principle of OY-TES-1 expression. The expression of OY-TES-1 was found in neurons, smooth muscle cells, and cardiac muscle cells from both fetuses and adults. The connective tissue showed no specific staining throughout the fetal and adult samples. With OY-TES-1-positive staining of the epithelium irregular, OY-TES-1 was strongly expressed in the epithelium of the skin and bladder, as well as hepatocytes, pancreatic islets, and acinous cells during the fetal stage but was not detected in the postnatal period. In contrast to the epithelium of blood vessels, the fetal and adult central hepatic vein and glomeruli showed negative expression of the OY-TES-1 protein. Sex-dimorphism was observed in the distribution of OY-TES-1 in male and female germ cells. Collectively, our results indicate that OY-TES-1 is a member of the cancer-testis antigen and autoantigen, with tissue-specific and period-specific expression patterns, revealing potential contributions of OY-TES-1 to the diagnosis and therapeutic treatment for neoplasms and infertility.
A Birth Cohort Study of Neurodevelopmental Outcomes from Birth to 2 Years of Age in Preterm Infants under 34 Weeks of Gestation
Authors: Li Hui-Li , Chen Ling-Ling , Qian Gang , Wang Wei-Shi , Feng Xiao-Na , Yu Mei-Qiao , Ren Lu-Zhong
Published: April 2022

Background. The tissues and organs of premature infants are immature and easily damaged by external adverse factors, leading to functional development disorders and abnormalities. Besides, the incidence of premature babies in various countries has an increasing trend, with the incidence rate exceeding 10%. Objective. This study aims to investigate the neurodevelopment and the incidence of various developmental delays, cerebral palsy, autism spectrum disorder, and audio-visual impairment in premature infants under 34 weeks of gestation from birth to 2 years of age, so as to provide the basis for early intervention of premature infants in the clinic. Methods A cohort of premature infants was established using 263 premature infants with a gestational age of 28–33 + 6 weeks who were born alive from March 1, 2018, to February 28, 2019, in four tertiary hospitals in Shenzhen. In addition, 263 full-term infants of the same sex who were born in the same period in the four hospitals were randomly selected and paired in a ratio of 1 : 1 as the control group. The subjects were assessed for neurodevelopment using the Gesell test scale at 6, 12, 18, and 24 months after birth (premature infants were corrected for months). We calculated the neurodevelopmental indicators of children in each month of age and the incidence of various developmental delays, cerebral palsy, autism spectrum disorder, and audio-visual impairment in the two groups. Results The results of this study showed that the cohort of premature infants with birth gestational age less than 34 weeks had higher adaptive, fine motor, and personal-social energy domain development quotient (DQ) values from the corrected gestational age of 6 months to the corrected gestational age of 24 months after birth compared with the full-term cohort. And it also achieved catch-up growth in neurological development, but the detection rates of neurodevelopmental abnormalities at the corrected gestational age of 12 and 24 months were higher than those in the full-term cohort. Conclusion It is important to reduce the disability rate and degree of premature infants by strengthening the systematic management, early promotion and supervision, as well as early intervention for preterm infants with developmental abnormalities who were born at gestational age less than 34 weeks after birth.
Mesenchymal Stem Cells Ameliorate Hyperglycemia in Type I Diabetic Developing Male Rats
Authors: Yousef Hany N. , Sakr Samia M. , Sabry Sahar A.
Published: April 2022

One of the most promising treatments for diabetes mellitus (DM) is stem cell therapy. This study is aimed at elucidating the antidiabetic effect of mesenchymal stem cells (MSCs) on streptozotocin- (STZ-) induced DM in developing male rats. Twenty-four male albino rats (4 weeks old) were divided into control, diabetic, diabetic+MSCs1 (received MSCs one week after STZ treatment), and diabetic+MSCs2 (received MSCs 4 weeks after STZ treatment). Diabetic rats showed marked impairment (

p
<
0.05

) in serum levels of glucose, insulin, C-peptide, glycosylated hemoglobin (HbA1c), malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS) in addition to disruption of the calculated values of homeostatic model assessment of insulin resistance (HOMA-IR), pancreatic β cell function (HOMA-β), and oxidative stress index (OSI). These biochemical alterations were confirmed by the histopathological and ultrastructural assessments which showed marked destructive effect on pancreatic islet cells. MSC therapy in an early stage reversed most of the biochemical, histological, and ultrastructural alterations in the STZ-induced diabetic model and restored the normal cellular population of most acinar cells and islet of Langerhans. These results indicate that MSC therapy of STZ-induced diabetic developing rats during an early stage has the capacity of β cell restoration and the control of blood glycemic homeostasis.
Identification of Volatile Compounds and Insecticidal Activity of Essential Oils from Origanum compactum Benth. and Rosmarinus officinalis L. against Callosobruchus maculatus (Fab.)
Authors: Baghouz Asmae , Bouchelta Yamna , Es-safi Imane , Bourhia Mohammed , Abdelfattah El Moussaoui , Alarfaj Abdullah A. , Hirad Abdurahman Hajinur , Nafidi Hiba-Allah , Guemmouh Raja
Published: April 2022

This work was undertaken to investigate the volatile compounds and insecticidal activity of essential oils (EOs) from Origanum compactum Benth. and Rosmarinus officinalis L. against the crop pest Callosobruchus maculatus (Fab.). Essential oils of Origanum compactum (EOC) and Rosmarinus officinalis L. (EOR) were extracted by use of hydrodistillation, and their volatile compounds were profiled by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of extracted EOC and EOR was evaluated against C. maculatus. GC-MS analysis revealed that carvacrol (70.88%) and 1,8-cineole (62.35%) were the major constituents of EOC and EOR, respectively. EOC exhibited a potent insecticidal activity with calculated LC50 values of 6.77 and 3.57 μL/L air, 24 and 48 h posttreatment, respectively. Comparable LC50 values were obtained for EOR recording 6.25 and 3.82 μL/L, 48 h posttreatment. The effects of fumigation by the tested EOs on fertility (egg hatching) and the emergence of adult C. maculatus were also investigated. Notably, EOC completely abolished egg fertility judged by the abrogation of emergence of adults, regardless of the tested dose. By contrast, EOR completely inhibited the fertility and the emergence of C. maculatus adults at the dose of 16 μL/10 g. The outcome of the present study highlights the utility of the EOs from O. compactum Benth. and R. officinalis L. as natural sources of effective and ecofriendly pest-control agents.
Influential Spreader Identification in Complex Networks Based on Network Connectivity and Efficiency
Authors: Qiang Rong , Yang Jianshe
Published: April 2022

Influential spreader identification is a vital research area in complex network theory, which has important influence on application and popularization. Each of the existing methods has its own advantages and disadvantages, and there are still various methods proposed to solve this issue. In this paper, we come up with a new centrality of influential spreader identification based on network connectivity and efficiency (CEC). The consequences of spreader deletion can be generally divided into two parts, one is that the connectivity of network topology is destroyed, and the other is that network’s performance is degraded, which makes the network unable to meet the functional requirement. Therefore, the relative changes of connectivity and efficiency of network before and after removing spreaders are used to present the influence of spreaders. We adopt susceptible-infected (SI) model, a well-known infectious disease model, to verify the effectiveness of CEC through the spreading ability simulation of spreaders in actual networks. And the simulation results demonstrate the superiority of CEC.
Effectiveness of Antimicrobial Stewardship Program in Long-Term Care: A Five-Year Prospective Single-Center Study
Authors: Alawi Maha Mahmoud , Tashkandi Wail A , Basheikh Mohamed A , Warshan Faten M , Ghobara Hazem Ahmed , Ramos Rosemarie B. , Guiriba Mary Leilani , Ayob Omar , Janah Safiah Saad , Sindi Anees Ahmad , Abdulhamid Ahmed Suheib Ali , Dammnan Salah , Azhar Esam Ibraheem , Rabaan Ali A. , Alnahdi Salma , Bamahakesh Maged Mohammed
Published: April 2022

Objective. To report the effectiveness of the antimicrobial stewardship program (ASP) in a long-term care (LTC) facility, by analyzing the change in antimicrobial consumption and cost and multidrug resistance (MDR) rates over a 5-year period. Method. A prospective interventional study was conducted at a 106-bed facility (nursing home: 100 beds and an intensive care unit (ICU): 6 beds). The ASP was designed and led by a multidisciplinary team including an infectious disease consultant, two clinical pharmacists, a clinical microbiologist, and an infection control preventionist. Five key performance indicators were monitored: (1) intravenous (IV)-to-oral switch rate, (2) consumption of restricted IV antimicrobials (raw consumption and defined daily doses (DDD) index), (3) cost of restricted IV antimicrobials, (4) antimicrobial sensitivity profiles, and (5) MDR rate among hospital-acquired infections (MDR-HAI). Result. A ∼5.5-fold enhancement of the IV-to-oral switch and a 40% reduction in the overall consumption of restricted IV antimicrobials were observed. Regarding the cost, the cumulative cost saving was estimated as 5.64 million SAR (US$1.50 million). Microbiologically, no significant change in antimicrobial sensitivity profiles was observed; however, a large-size reduction in the MDR-HAI rate was observed, notably in ICU where it declined from 3.22 per 1,000 patient days, in 2015, to 1.14 per 1,000 patient days in 2020. Interestingly, the yearly overall MDR rate was strongly correlated with the level of antimicrobial consumption. Conclusion. The implementation of a multidisciplinary ASP in LTC facilities should be further encouraged, with emphasis on physicians’ education and active involvement to enhance the success of the strategy.
Hierarchical Optimization Scheduling of Active Demand Response for Distribution Networks in 5G Base Stations
Authors: Liu Guangyu , Zhang Haonan , Shang Ruiheng , Wu Zhenyu , Song Qingdong
Published: April 2022

The study aims to solve the problem that the traditional scheduling optimization model does not apply to the multimicrogrid systems in the 5th generation mobile networks (5G). First, the response characteristics of the 5G base station energy storage demand are analyzed. Second, a microgrid hybrid power supply system is proposed. Third, a multimicrogrid demand response hierarchical optimal scheduling model based on the game is constructed, and the game interaction mechanism between various stakeholders in the demand response is studied. Finally, the strategy of each microgrid in the IEEE-9 bus system in the game bidding is simulated by a genetic algorithm (GA), and the simulation experiment is carried out by Matlab. The results show that (1) after the optimization of the multimicrogrid system, the overall load of the microgrid is reduced, the independent energy optimization is carried out according to the energy access of each microgrid, and renewable energy is fully used. (2) Based on the game-based time-sharing bidding strategy, the system gives priority to the low-cost microgrid for power supply and saves the cost. (3) The load transfer capacity of the three microgrids obtained by the model are 132.7 kW, 47.1 kW, and 46.4 kW, which is within the actual load range of each microgrid; their electricity sales are 665.8 kWh, 2053.3 kWh, and 1668.2 kWh; and their income is 132.45 CNY, 411.72 CNY, and 354.63 CNY, respectively. This shows that the game equilibrium index makes the power sales of each microgrid proportional to its income, which ensures the fair and effective scheduling in the bidding process. The study provides technical support for the construction of a 5G base station and the active demand response scheduling optimization of distribution networks.
Efficacy of Glucocorticoid plus Intravenous Immunoglobulin in Children with Immunoglobulin-Insensitive Kawasaki Disease
Authors: Ma Yongmei , Zhang Jingjing , Fan Rong
Published: April 2022

This study mainly analyzes the clinical effect of glucocorticoid (GC) plus intravenous immunoglobulin (IVIG) in treating children with immunoglobulin (Ig)-insensitive Kawasaki disease (KD). From September 2013 to November 2021, 86 Ig-insensitive KD children were selected, including 46 children (observation group, Obs) treated with GC plus IVIG, and 40 children (control group, Con) treated with IVIG. The symptom (fever and fever) resolution time, inflammatory factors (C-reactive protein, CRP; procalcitonin, PCT; interleukin-6, IL-6), immune indicators (CD3+, CD4+, CD8+ T lymphocytes CD3+, CD4+, and CD4+/CD8+), and incidence of adverse reactions were compared between the groups. The results identified shorter fever and rash resolution time in Obs compared with Con. The posttreatment CRP, PCT, IL-6, and CD8+ and the incidence of adverse events reduced notably in Obs and were lower than Con, while CD3+, CD4+, and CD4+/CD8+ elevated statistically and were higher than that of Con. Our results indicate that GC plus IVIG can significantly promote symptom resolution, alleviate inflammatory response, and improve immune function in children with Ig-insensitivity KD, with favorable safety and clinical promotion value.
Convención Constituyente Visión de normas autónomas territoriales que afectan la equidad tributaria
Authors: Borges Humberto
Published: April 2022

En la Constituyente se ha estado discutiendo la situación de la equidad tributaria y existe la idea de entregarle autonomía en este sentido a los territorios. En este artículo, mostraremos el contraste entre la iniciativa popular y la iniciativa interna de los constituyentes que discuten al respecto. La iniciativa popular llamada “Servicios públicos universales y de calidad y política fiscal universal y justa para la garantía de derechos sociales” (IP, 18.202) contó con 15.241 apoyos. Continuar leyendo...
Induction of Synthetic Lethality by Activation of Mitochondrial ClpP and Inhibition of HDAC1/2 in Glioblastoma
Authors: Nguyen Trang T.T. , Shang Enyuan , Schiffgens Salveena , Torrini Consuelo , Shu Chang , Akman Hasan Orhan , Prabhu Varun V. , Allen Joshua E. , Westhoff Mike-Andrew , Karpel-Massler Georg , Siegelin Markus D.
Published: April 2022

Purpose:

Novel therapeutic targets are critical to unravel for the most common primary brain tumor in adults, glioblastoma (GBM). We have identified a novel synthetic lethal interaction between ClpP activation and HDAC1/2 inhibition that converges on GBM energy metabolism.

Experimental Design:

Transcriptome, metabolite, and U-13C-glucose tracing analyses were utilized in patient-derived xenograft (PDX) models of GBM. Orthotopic GBM models were used for in vivo studies.

Results:

We showed that activation of the mitochondrial ClpP protease by mutant ClpP (Y118A) or through utilization of second-generation imipridone compounds (ONC206 and ONC212) in combination with genetic interference of HDAC1 and HDAC2 as well as with global (panobinostat) or selective (romidepsin) HDAC inhibitors caused synergistic reduction of viability in GBM model systems, which was mediated by interference with tricarboxylic acid cycle activity and GBM cell respiration. This effect was partially mediated by activation of apoptosis along with activation of caspases regulated chiefly by Bcl-xL and Mcl-1. Knockdown of the ClpP protease or ectopic expression of a ClpP D190A mutant substantially rescued from the inhibition of oxidative energy metabolism as well as from the reduction of cellular viability by ClpP activators and the combination treatment, respectively. Finally, utilizing GBM PDX models, we demonstrated that the combination treatment of HDAC inhibitors and imipridones prolonged host survival more potently than single treatments or vehicle in vivo.

Conclusions:

Collectively, these observations suggest that the efficacy of HDAC inhibitors might be significantly enhanced through ClpP activators in model systems of human GBM.
Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors
Authors: Muik Alexander , Garralda Elena , Altintas Isil , Gieseke Friederike , Geva Ravit , Ben-Ami Eytan , Maurice-Dror Corinne , Calvo Emiliano , LoRusso Patricia M. , Alonso Guzman , Rodriguez-Ruiz Maria E. , Schoedel Kristina B. , Blum Jordan M. , Sänger Bianca , Salcedo Theodora W. , Burm Saskia M. , Stanganello Eliana , Verzijl Dennis , Vascotto Fulvia , Sette Angelica , Quinkhardt Juliane , Plantinga Theo S. , Toker Aras , van den Brink Edward N. , Fereshteh Mark , Diken Mustafa , Satijn David , Kreiter Sebastian , Breij Esther C.W. , Bajaj Gaurav , Lagkadinou Eleni , Sasser Kate , Türeci Özlem , Forssmann Ulf , Ahmadi Tahamtan , Şahin Uğur , Jure-Kunkel Maria , Melero Ignacio
Published: April 2022

Checkpoint inhibitors (CPI) have revolutionized the treatment paradigm for advanced solid tumors; however, there remains an opportunity to improve response rates and outcomes. In preclinical models, 4-1BB costimulation synergizes with CPIs targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis by activating cytotoxic T-cell–mediated antitumor immunity. DuoBody-PD-L1×4-1BB (GEN1046) is an investigational, first-in-class bispecific immunotherapy agent designed to act on both pathways by combining simultaneous and complementary PD-L1 blockade and conditional 4-1BB stimulation in one molecule. GEN1046 induced T-cell proliferation, cytokine production, and antigen-specific T-cell–mediated cytotoxicity superior to clinically approved PD-(L)1 antibodies in human T-cell cultures and exerted potent antitumor activity in transplantable mouse tumor models. In dose escalation of the ongoing first-in-human study in heavily pretreated patients with advanced refractory solid tumors (NCT03917381), GEN1046 demonstrated pharmacodynamic immune effects in peripheral blood consistent with its mechanism of action, manageable safety, and early clinical activity [disease control rate: 65.6% (40/61)], including patients resistant to prior PD-(L)1 immunotherapy.

Significance:

DuoBody-PD-L1×4-1BB (GEN1046) is a first-in-class bispecific immunotherapy with a manageable safety profile and encouraging preclinical and early clinical activity. With its ability to confer clinical benefit in tumors typically less sensitive to CPIs, GEN1046 may fill a clinical gap in CPI-relapsed or refractory disease or as a combination therapy with CPIs.

See related commentary by Li et al., p. 1184.

This article is highlighted in the In This Issue feature, p. 1171
Non-Atopic Chronic Nodular Prurigo (Prurigo Nodularis Hyde): A Systematic Review of Best-Evidenced Treatment Options
Authors: Frølunde Anne Sofie , Wiis Malthe Alexander Knudsgaard , Ben Abdallah Hakim , Elsgaard Stine , Danielsen Anna Kathrine , Deleuran Mette , Vestergaard Christian
Published: April 2022

Background: Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood, and the condition is difficult to treat with no targeted therapies. The aim of this systematic review was to review the evidence of therapies for non-atopic CNPG and conduct a meta-analysis of the results. Summary: We conducted a systematic review of the literature concerning effect of treatment for non-atopic CNPG. Due to few randomized controlled trials (RCTs) and case series, the literature was unfortunately too sparse to conduct a meta-analysis of the results. Instead, we thoroughly report important data from the three existing RCTs and 6 case studies with more than 15 patients. Evaluated therapies include nemolizumab, aprepitant, topical therapy with hydrocortisone and pimecrolimus, thalidomide, UVA phototherapy, pregabalin, and naltrexone. Included RCTs and case studies all had a heterogeneous methodology making direct comparison almost impossible. Key Messages: There is sparse evidence for the currently used therapies for non-atopic CNPG. Several RCTs on new therapies are running or in the pipeline, hopefully providing new, effective, and targeted treatment possibilities for CNPG patients both with and without an atopic predisposition.
The Effects of Consuming Cannabis Flower for Treatment of Fatigue
Authors: Li Xiaoxue , Diviant Jegason P. , Stith Sarah S. , Brockelman Franco , Keeling Keenan , Hall Branden , Vigil Jacob M.
Published: April 2022

Objectives: We measure for the first time how commercially available Cannabis flower products affect feelings of fatigue. Methods: A total of 1,224 people recorded 3,922 Cannabis flower self-administration sessions between June 6, 2016, and August 7, 2019, using the Releaf App. Usage sessions included real-time subjective changes in fatigue intensity levels prior to and following Cannabis consumption, Cannabis flower characteristics (labeled phenotype, cannabinoid potency levels), combustion method, and any potential experienced side effects. Results: On average, 91.94% of people experienced decreased fatigue following consumption with an average symptom intensity reduction of 3.48 points on a 0–10 visual analog scale (SD = 2.70, d = 1.60, p < 0.001). While labeled plant phenotypes (“C. indica,” “C. sativa,” or “hybrid”) did not differ in symptom relief, people that used joints to combust the flower reported greater symptom relief than pipe or vaporizer users. Across cannabinoid levels, tetrahydrocannabinol, and cannabidiol levels were generally not associated with changes in symptom intensity levels. Cannabis use was associated with several negative side effects that correspond to increased feelings of fatigue (e.g., feeling unmotivated, couch-locked) among a minority of users (<24% of users), with slightly more users (up to 37%) experiencing a positive side effect that corresponds to increased energy (e.g., feeling active, energetic, frisky, or productive). Conclusions: The findings suggest that the majority of patients experience decreased fatigue from consumption of Cannabis flower consumed in vivo, although the magnitude of the effect and extent of side effects experienced likely vary with individuals’ metabolic states and the synergistic chemotypic properties of the plant.
Gender Differences in Comorbidities and Attitudes Regarding Weight Control among Young Adults with Obesity in Korea
Authors: Kang Seo Young , Park Hye Soon
Published: April 2022

Introduction: Obesity in young adulthood increases the risk for premature death, and the prevalence of obesity rapidly increasing among young adults, particularly in young men. We evaluated the gender differences in accompanying comorbidities and attitudes regarding weight control among young Korean adults with obesity. Materials and Methods: We analyzed 2,050 young adults with obesity (1,325 men and 725 women) in the 7th KNHANES (2016–2018) aged 19–44 years, with body mass indexes (BMIs) ≥25.0 kg/m2. The odds ratios (ORs) and 95% confidence intervals (CIs) for poor lifestyle factors and accompanying illnesses as well as self-perceived weight status, weight control efforts, and weight control strategies in men compared to those in women were calculated by multivariate logistic regression analysis. Results: The mean BMIs and waist circumferences were 28.2 ± 0.1 kg/m2 and 93.6 ± 0.2 cm and 28.6 ± 0.1 kg/m2 and 88.7 ± 0.4 cm, in men and women, respectively. The ORs and 95% CIs for abdominal obesity (1.52, 1.11–2.07), hypertension (3.11, 2.20–4.40), hypercholesterolemia (1.45, 1.09–1.93), hypertriglyceridemia (3.37, 2.38–4.78), and elevated alanine transaminase concentration (6.53, 4.56–9.36) were higher in young men compared to those in young women. Despite the higher prevalences of comorbid conditions, the odds of inappropriate weight perception (8.13, 4.17–15.86), lack of weight control efforts (2.20, 1.71–2.84), lack of diet therapy (1.56, 1.13–2.16), lack of pharmacotherapy (13.27, 6.82–25.79), heavy drinking (1.32, 1.02–1.72), current smoking (6.92, 5.00–9.59), and frequent eating out (4.38, 3.35–5.71) were higher among men. However, the odds of not engaging in exercise (0.48, 0.35–0.64) were lower among men compared to that in women. Discussion: Despite their higher prevalences of comorbidities, appropriate weight perception and weight control efforts are insufficient in young men with obesity. These gender differences should be considered to provide tailored programs for weight reduction in young adults with obesity.
Association between Endocrine Disorders and Severe COVID-19 Disease in Pediatric Patients
Authors: Banull Nicholas R. , Reich Patrick J. , Anka Carine , May Jennifer , Wharton Kathleen , Kallogjeri Dorina , Shimony Hope , Arbeláez Ana María
Published: April 2022

Introduction: Though severe illness due to COVID-19 is uncommon in children, there is an urgent need to better determine the risk factors for disease severity in youth. This study aims to determine the impact a preexisting endocrine diagnosis has on severity of COVID-19 presentation in youth. Methods: The cross-sectional chart review study included all patients less than 25 years old with a positive SARS-CoV-2 PCR at St. Louis Children’s Hospital between March 2020 and February 2021. Electronic medical record data for analysis included patient demographics, BMI percentile, inpatient hospitalization or admission to the pediatric intensive care unit (PICU), and the presence of a preexisting endocrine diagnosis such as diabetes mellitus (type 1 and type 2), adrenal insufficiency, and hypothyroidism. Two outcome measures were analyzed in multivariate analysis: inpatient admission and PICU admission. Adjusted odds ratios with a 95% CI were calculated using binary logistic regression, along with p values after Wald χ2 analysis. Results: 390 patients were included in the study. Mean age was 123.1 (±82.2) months old. 50.3% of patients were hospitalized, and 12.1% of patients were admitted to intensive care. Preexisting diagnoses of diabetes mellitus, obesity, and hypothyroidism were associated with an increased risk of hospital and ICU admission, independent of socioeconomic status. Discussion/Conclusion: This study provides evidence that unvaccinated youth with a preexisting diagnosis of obesity, hypothyroidism, or diabetes mellitus infected with COVID-19 are more likely to have a more severe clinical presentation requiring inpatient hospital admission and/or intensive care.
Notas sobre a proibição de tratamento cruel, desumano e degradante às pessoas privadas de liberdade, segundo a jurisprudência das Cortes Europeia e Interamericana de Direitos Humanos
Authors: Gomes Mariângela Gama de Magalhães
Published: April 2022

A partir da leitura de alguns casos julgados pelas Cortes Europeia e Interamericana de Direitos Humanos, propõe-se uma análise do que se entende pela proibição de tratamento cruel, desumano e degradante às pessoas privadas de liberdade prevista nos instrumentos internacionais de proteção de direitos humanos. Os casos apresentados exemplificam, de maneira concreta, o alcance do referido dispositivo convencional, permitindo compreender os critérios gerais utilizados para a avaliação do tratamento dispensado pelo Estado aos detentos, assim como situações específicas de superlotação, tortura, isolamento, incomunicabilidade, e casos de incêndios, rebeliões e massacres nos estabelecimentos penitenciários; os direitos à saúde, à privacidade e às mínimas condições de higiene são igualmente abordados.
Georg-Friedrich Von Martens (1756-1821) e a consolidação histórica do direito internacional clássico
Authors: Casella Paulo Borba
Published: April 2022

A obra de Von Martens se inscreve como o final da fase ‘clássica’ do direito internacional. Na evolução da disciplina, muitos ainda parecem considerar o modelo ‘clássico’, como o único possível, para o direito internacional. Essa experiência, temporalmente circunscrita, historicamente prepara e dá sustentação, para a ulterior evolução do direito internacional, na fase seguinte, do Direito internacional no tempo do concerto europeu.
Terrorismo de Estado
Authors: Ferreira Júnior Geraldo Miniuci
Published: April 2022

Este artigo explora o conceito de “terrorismo de Estado”. O que significa? Sob que condições seria possível uma ação violenta receber semelhante qualificação? Como colocar o Estado, tradicionalmente vítima do terrorismo, na condição de seu perpetrador? A fim de responder essas questões, iremos, na seção I, apresentar os modelos interpretativos que podem ser usado para avaliar o problema: de um lado, o ortodoxo, que tem na pergunta, como ocorre o terrorismo, sua questão principal; de outro, o modelo crítico, em que a questão é esta, por que ocorre o terrorismo? Na seção II, usaremos o modelo crítico e trataremos da noção de terrorismo de Estado.
Governança e interculturalidade: a complementaridade entre a análise sociológica e a antropológica na apreensão de uma interação complexa
Authors: Villas Bôas Filho Orlando
Published: April 2022

Este artigo pretende analisar o fenômeno da governança diante da interculturalidade. Assim, inicialmente, examina o delineamento conceitual que lhe é dado pela sociologia jurídica. Em seguida, mediante o recurso à abordagem antropológica, discute a ambivalência que perpassa a governança no horizonte da interculturalidade. Por fim, em termos conclusivos, enfatiza o caráter frutífero da complementaridade entre as perspectivas sociológica e antropológica, no horizonte de um campo de pesquisa interdisciplinar.