bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical Modelling of Drug Interaction on Evolution of Antibiotic Resistance: An Analytical Approach
Authors: Nashebi Ramin , Sari Murat , Kotil Seyfullah 
Published: April 2022

Abstract
The rapid spread of antibiotic-resistant pathogens has prompted drug combinations to maintain clinical efficacy and combat the development of resistance. Drugs interact to increase (synergistic) or decrease (antagonistic) the effect of the combined therapy. Furthermore, the interactions of the two drugs can change as the bacteria evolves from the wild type (WT) to the mutant type (MT). Experimental studies have shown that the evolution of resistance is impeded if drugs interact antagonistically in the WT. In contrast, other studies have shown that antagonistic interactions in the MT speed up the resistance's emergence. Theoretical works investigated the effect of WT drug interactions on resistance. A fundamental question is how the different combination of drug interactions in WT and the MT influences antimicrobial resistance. Here we analyze a mathematical model that captures any combination of drug interactions in WT and the MT. The novelty of this work is to examine the association between synergistic and antagonistic interaction of antibiotics for wild-type (sensitive bacteria) and mutants (resistant bacteria) on the growth rate of resistant strains. The most important contribution is to clarify that antagonistic interaction against the wild type has a more critical role in slowing the growth rate of resistant bacteria. The antagonistic interaction in the MT speeds up evolution but minimally. Our results suggest that it would be more appropriate to consider the nature of the drug interactions for the WT when designing combination therapy.
Less acetabular coverage predicts the failure of core decompression for osteonecrosis of the femoral head: a retrospective cohort study
Authors: Huang Kai , Zhang Qing-Yi , Tan Jie , Wang Gang , Yang Jing , Xie Hui-Qi , Zeng Yi 
Published: April 2022

Abstract

Background: It is unclear whether less acetabular coverage is associated with the failure of core decompression (CD) for osteonecrosis of the femoral head (ONFH). This study aimed to (1) investigate the clinical outcomes of CD for ONFH and (2) determine what factors, especially acetabular anatomical parameters, predict the failure of CD.Methods: We retrospectively reviewed 322 consecutive CDs in 214 patients diagnosed with pre-collapse ONFH, with a mean follow-up of 69.1±37.5 months. The Kaplan-Meier method was used to evaluate the survival rate of CD for ONFH. Univariate and multivariate logistic regression analyses were conducted to identify the potential risk factors for the failure of CD. Receiver operating characteristic (ROC) curve analysis was further performed with conversion to total hip arthroplasty (THA) as the endpoint to determine the cutoff value, sensitivity and specificity of these factors.Results: The overall 5-year survival rate of CD for ONFH was 70.1% (95% CI 65.0-75.6) with progression of collapse as the endpoint and 80.3% (95% CI 75.7-85.1) with conversion to THA as the endpoint. Univariate and multivariate logistic regression analyses showed that less acetabular coverage with a lower center-edge angle (CEA) and acetabular head index (AHI) was significantly associated with the progression of collapse and conversion to THA. The ROC curve analysis with conversion to THA as the endpoint revealed that the cutoff values for CEA and AHI were 27.2° (sensitivity=70.9%, specificity=70.5%, area under the curve (AUC)=0.765) and 79.7 (sensitivity=78.9%, specificity=65.6%, AUC=0.778), respectivelyConclusion: CD showed satisfactory clinical outcomes for pre-collapse ONFH, where less acetabular coverage with a CEA <27.2° or AHI <79.7 was identified as an independent risk factor for the failure of CD.Trial registration: ChiCTR2100053471 (November 22, 2021)
M2 macrophage-derived exosome facilitates metastasis in non-small-cell lung cancer via delivering integrin αvβ3
Authors: Huang Lamei , Zhang Jianye , Wang Xueping , Su Chaoyue , Wu Shaocong , Yang Chuan , Luo Min , Wang Fang , Fu Liwu 
Published: April 2022

Abstract
Background
The most prevalent cause of cancer death is metastasis. Immunological components of tumour microenvironment, especially tumour-associated macrophages, play a vital role in cancer metastasis. However, the underlying mechanisms of tumour-associated macrophages on non-small-cell lung cancer (NSCLC) metastasis remain largely unexplored.
Methods
The distribution of macrophages in tumor microenvironment, especially in lung cancer, was analyzed by online database and immunohistochemistry. The model of M2 macrophage was successfully established in vitro and M2 macrophage-derived exosomes were identified by transmission electron microscope imaging, nanoparticle tracking analysis and western blot. The role of M2 macrophage-derived exosomes (M2-exos) in promoting metastasis of lung cancer cells was identified by transwell assay, wound healing assay, immunofluorescence in vitro, and by tumor model in vivo. The mechanism that M2-exos facilitates metastasis via delivering integrin αvβ3 and activating the FAK signaling was investigated using western blot, transwell assays, immunofluorescence assays. Finally, the expression levels of integrin αvβ3 were assessed in clinical samples by immunohistochemistry.
Results
We demonstrated that M2-polarized phenotypic macrophages facilitate the migration and invasion of cancer cells in vitro and in vivo through intercellular delivering M2-exos. Importantly, we found that M2-exos had considerably higher levels of integrin αvβ3. The impact of M2 macrophage-mediated invasion and migration of NSCLC cells was clearly decreased when integrin αvβ3 was blocked. Mechanistically, exosomal integrin αvβ3 produced from M2 macrophages successfully triggered the FAK signaling pathway in recipient cells, boosting the migratory and invasive abilities of NSCLC cells. Clinically, we found that metastatic NSCLC patients had greater integrin αvβ3 expression, which was associated with worse prognosis.
Conclusions
This study reveals a novel mechanism that M2 macrophage-derived exosomal integrin αvβ3 significantly increased NSCLC cells migration and invasion. integrin αvβ3 can be used as a potential prognostic marker, and blocking integrin αvβ3 could be a viable treatment option for preventing tumour progression and metastasis.
Analysis of high temperature oxidation performance of DD6 under different aging treatment
Authors: Li Xiaopeng , Xie Youshui , Huang Yao , Sun Yanwen , Zhao Chengzhi , Zhang Hexin X. 
Published: April 2022

Abstract
In accordance with the national standard HB 5258-83 "Antioxidant determination test method for steel and high temperature alloy", this paper implements high temperature oxidation performance tests of single crystal high temperature alloy. Three different heat-treated single crystal samples were oxidized at 900℃ and 1000℃ for 125h. The oxidative properties were determined by discontinuous weighing method and cyclic oxidation method. The oxidation of the sample after oxidation was analyzed by XRD, and SEM, EDS was used to study the composition and morphology of the surface of and longitudinal section of the sample. At 900℃ and 1000℃, the heat treatment of the sample with the best oxidation resistance is SHT + 1100℃/30min AC, and the heat treatment of the sample with the worst oxidation resistance is SHT + 1100℃/10min AC.
Association of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with outcomes in stroke patients achieving successful recanalization by endovascular thrombectomy
Authors: Ma Jin , Guo Wenting , Xu Jiali , Li Sijie , Ren Changhong , Wu Longfei , Wu Chuanjie , Li Chuanhui , Chen Jian , Duan Jiangang , Ma Qingfeng , Song Haiqing , Zhao Wenbo , Ji Xunming 
Published: April 2022

Abstract
Serum inflammatory biomarkers have been found to play crucial roles in the development of acute ischemic stroke (AIS). In this study, we explored the association between inflammatory biomarkers, such as platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), and functional outcomes in AIS patients who achieved successful recanalization. Patients with AIS who underwent endovascular thrombectomy (EVT) therapy and achieved a modified thrombolysis in cerebral infarction scale of 2b or 3 were screened from a prospective cohort at our institution between January 2013 and June 2021. Data on blood parameters and other baseline characteristics were collected. Unfavorable outcomes were defined as a modified Rankin Scale of 3-6 at 3 months. Multivariable logistic regression analysis was performed to explore the effects of PLR, NLR, and MLR on neurological functional outcomes. We enrolled 796 patients, of whom 331 (41.6%) had favorable outcomes and 465 (58.4%) had unfavorable outcomes. Patients with unfavorable outcomes had higher PLR (median, 168.89 vs. 153.90, p = 0.002), NLR (median, 6.57 vs. 4.85, p < 0.001), and MLR (median, 0.32 vs. 0.28, p < 0.001). After adjusting for confounding variables, a higher NLR (OR, 1.076; 95% confidence interval [CI], 1.037-1.117; p < 0.001) and PLR (OR, 1.001; 95%CI, 1.000-1.003; p = 0.045) were significantly associated with unfavorable outcomes. The area under the receiver operating characteristic curve of NLR and PLR was 0.622 and 0.564, respectively. Overall, our results indicate that higher PLR and NLR were independently associated with unfavorable functional outcomes in AIS patients with successful recanalization after EVT, but the underlying mechanisms remain to be investigated.
Investigation of respiratory viruses by multiplex PCR method in the community suggested reciprocal virus transmission between children and adults
Authors: Nagasawa Masayuki 
Published: April 2022

Abstract
The observational study of respiratory virus infection for children has already been reported, but there are few reports that examined both children and adults simultaneously in the community. We performed a multiplex PCR (polymerase-chain reaction) assay of respiratory viruses by using FilmArray respiratory panel version 2.1 for 248 children (under 15 years old) and 5,354 adults (15 years old or older) who were admitted or visited our hospital with respiratory symptoms and/or fever from December 2020 to November 2021. During this period, a seasonal outbreak of respiratory syncytial virus (RSV) and parainfluenza virus 3 (PI3) was found as well as a pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In adults, viruses were detected in 6.8% (364/5,354), and SARS-CoV-2 accounted for 228 cases. Only two cases presented multiple viruses. In children, viruses were detected in 64.9% (161/248), while 75.4% (135/179) were under 5 years old. Multiple viruses were detected in 26 cases, all of which were under 5 years old. SARS-CoV-2 was positive in six children. RSV prevailed both in children and adults simultaneously, while the PI3 outbreak was found first in children, followed by adults three weeks later. Rhinovirus/enterovirus (RV/EV) was detected throughout the year with some fluctuation and was mostly found in children under 5 years old and in adults aged between 20s and 30s, which suggested reciprocal virus transmission between the children and the parents.
Four economic principles of just sustainability transition
Authors: Dombi Mihály , Fahid Aldebei Faisal Mohammad , Harazin Piroska , Karcagi-Kováts Andrea , Cao Zhi 
Published: April 2022

Abstract

Equitable income distribution is desirable for moral, economic, and social reasons. Recent studies, however, indicate that improved income allocation will result in increased environmental impacts due to our socio-economic system's current settings. Therefore, we explored the key aspects of a system that can more evenly reallocate natural and economic resources while reducing negative environmental impacts. We found that the capital is extremely important as a means of material flows and stocks. Thus, effective policy interventions should target mechanisms at this very market. Based on a comprehensive literature review and statistical analyses at various levels, we proposed a four-step policy framework that includes reducing and targeted savings, reshaping governments' spatial decisions and role in the housing market, and changing the rates of depreciation in income tax legislation used globally.
PIKfyve-specific inhibitors restrict replication of multiple human coronaviruses in vitro but not in a murine model of COVID-19
Authors: Logue James , Chakraborty Arup R. , Johnson Robert , Goyal Girija , Taylor Louis J. , Baracco Lauren , McGrath Marisa E. , Haupt Robert , Rodas Melissa , Furlong Brooke A. , Soong Mercy , Prabhala Pranav , Horvath Viktor , Carlson Kenneth E. , Weston Stuart , Ingber Donald E. , DePamphilis Melvin L. , Frieman Matthew B. 
Published: April 2022

Abstract
The ongoing COVID-19 pandemic has claimed more than 6 million lives and continues to test the world economy and healthcare systems. To combat this pandemic, the biological research community has shifted efforts to the development of medical countermeasures, including vaccines and therapeutics. However, to date, the only small molecules approved for the treatment of COVID-19 in the United States are the nucleoside analogue Remdesivir and the protease inhibitor Paxlovid, though multiple compounds have received Emergency Use Authorization and many more are currently being tested in human efficacy trials. One such compound, Apilimod, is being considered as a COVID-19 therapeutic in a Phase II efficacy trial. However, at the time of writing, there are no published efficacy data in human trials or animal COVID-19 models. Here we show that, while Apilimod and other PIKfyve inhibitors have potent antiviral activity in various cell lines against multiple human coronaviruses, these compounds worsen disease in a COVID-19 murine model when given prophylactically or therapeutically.
Ultrasound control of the feeding tube position in newborns: a prospective study
Authors: Smirnov O. G. , Gorbachev Vladimir I. , Aleynikova N. G. , Braginа N. V. 
Published: April 2022

INTRODUCTION. In the last decade, there has been a rethinking of the value of nutritional support for neonatal intensive care patients. According to the American and European guidelines for nutritional therapy, enteral feeding is the preferred method of nutrition for patients with a functioning gastrointestinal tract. Preterm infants in critical ill have a low tolerance to during gastric feeding. Research shows that the use of transpiloric feeding is comparable in effectiveness to operative fundoplication. X-ray control method is used to confirm the correct position of the transpyloric tube. OBJECTIVES. The goal of this study was to evaluate the effectiveness and safety of ultrasound control of the transpyloric tube position in comparison with X-ray examination. MATERIALS AND METHODS. All patients included in the study had a low tolerance to enteral feeding through a gastric tube. The use of ultrasound during this manipulation provided an alternative method for monitoring the position of the tube without the X-ray control. Before the tube insertion procedure, the pyloric canal and postpyloric area were visualized in 100 % of patients. RESULTS. After the manipulation, according to sonography data, in 94.1 % of patients, the transpyloric tube was located outside the pyloric part of the stomach (in the duodenum). In more than half of the cases, there was a complete coincidence of the conclusions of radiography and ultrasound examination. At 41.2 % of cases, the radiologist could not determine the exact location of the distal end of the tube between the duodenum and jejunum. CONCLUSIONS. Usage transpyloric tube of ill infants may lead to improved treatment outcomes. The obtained data indicate that ultrasound imaging of the tube is statistically more reliable than X-ray control. The use of ultrasound to visualize the process of installing tube may exclude the additional use of radiography.
Critical Strategies for Drug Precipitation Inhibition: A Review with the
Focus on Poorly Soluble Drugs
Authors: Kadu Pramod , Parmar Tanvi , Kale Pravin 
Published: April 2022

Abstract:
An oral route for drug administration is a more suitable route because of its ease of administration,
pain avoidance, patient compliance, accommodation of various types of drug molecules, etc.
But there are many factors affecting the oral absorption of the drugs. The main factor associated with
oral absorption is drug solubility. Many new chemical molecules are poorly soluble in nature and can
be included in BCS classes II and IV. For the administration of these drugs through the oral route, it was
found that solubility is the rate limiting step. The low solubility of these drugs tends to cause precipitation
in the gastrointestinaltract (GIT), affecting their bioavailability. Drug precipitation may be triggered
by many factors such as insolubility of the drug in co-solvent, drug-excipient interactions, physiochemical
properties of the drug, sudden change in the pH of the environment, incompatibility with the surfactant,
etc. Precipitation of a drug may occur in two stages, formation of nucleation and crystal growth. To
overcome precipitation, there are many strategies such as the use of polymers, the addition of surfactants,
modulating drug loading and solubilizing capacity, change in the pH of the environment, etc. In
this review, the causes of precipitation and diverse strategies of precipitation inhibition are critically
reviewed.
Smart Advancements for Targeting Solid Tumors via Protein and Peptide
Drug Delivery (PPD)
Authors: Singh Siddharth , Sanwal Priyanka , Bhargava Samir , Behera Ashok , Upadhyay Shuchi , Akhter Md. Habban , Gupta Manish , Gupta Shraddha Manish 
Published: April 2022

Abstract:
Proteins and peptides possess considerable potential in treating solid tumors because of their
unique properties. At present, there are over 100 peptide-based formulations on the market. Today,
peptides and proteins are in more demand due to their selective nature and high target-binding efficiency.
Targeting solid tumors with compounds of molecular weight less than 10 kDa are much more desirable
because they undergo excessive penetration in view of the fact that they are small sized. The solid
tumors have thick tissues and possess excessive interstitial fluid pressure, because of which high molecular
compounds cannot enter. The properties of proteins and peptides induce low toxic effects and
lessen the major side effects caused by chemical-based drugs. However, their delivery is quite challenging
as most proteins and peptides stop functioning therapeutically when following a parenteral route of
administration. This paper elaborates on the importance of new age formulations of peptides and proteins
followed by their recently documented advancements that increase their stability and delay their
metabolism, which helps to target solid tumors.
An Overview of Potential Applications for Nanotechnology, Probiotics, and Medicinal Plants in Infertility Problems
Authors: Salmany Nooshin , Lotfi Hajie , Keyhanmanesh Rana , Ghiasi Rafighe 
Published: April 2022

Abstract:Various assisted reproductive technologies (ART) are applied in the infertility treatment. However, considerable attention is addressed to use alternative approaches, such as non-biotechnology, probiotics, and traditional medicinal plants to treat cancerous and non-cancerous cases of infertility. Nanotechnology was remarkably aided in treatment, diagnosis, and drug delivery. The existing data of this technology might demonstrate the enormous potential of nanomaterials and their viability in clinical trials for the study of reproductive issues. In order to understand the function of the microbiome in infertility and the many good effects of probiotics in illnesses such as colon cancer, obesity, diabetes, and inflammatory bowel disease, research on infertility must be conducted. Healthy reproductive systems are important for successful fertility in males and females, and using probiotics can help reduce the associated complications. Besides, in vivo models are required to determine the probiotics proper administration, identify the functional species, effective doses, administration forms, and the effects of their combination with conventional antibiotics. In addition, medicinal herbs should be explored, notably in the treatment of male infertility and the improvement of sperm abnormalities. The antioxidant capacity, anti-inflammatory reactions, increased sperm production, and increased testosterone levels in the blood are all examples of medicinal plant benefits. More study is needed to establish specific findings on which substances are involved and have effective and safe fertility potential. This review presents an overview of potential applications for nanotechnology, probiotics, and medicinal plants in infertility, discussing the advantages, their feasibility, and associated concerns, which demand more investigations to set of clinical applications.
Inhibitory Effects of Linum usitatissimum Alkaloid on Inflammatory and Nociceptive Responses in Mice
Authors: Bribi Noureddine , Merakeb Mohamed Sofiane , Ferhat Riad , Yanat Betitera 
Published: April 2022

Background:Linum usitatissimum is widely used in traditional medicine for the treatment of inflammation, cardiovascular and respiratory diseases.Methods:Acute oral toxicity, anti-inflammatory and analgesic effects of total alkaloid extract from Linum usitatissimum seeds (ALU) were investigated in vivo. Xylene induced ear edema was used to determine anti-inflammatory effect, and acetic acid-induced writhing, formalin induced paw licking and tail-immersion tests were used to investigate analgesic activity.Results:Oral administration of ALU (50, 100 and 200 mg/kg) produced anti-inflammatory and analgesic effects. ALU significantly diminished the edema induced by xylene. ALU also significantly reduced the abdominal construction induced by acetic acid. Furthermore, ALU also inhibited responses in both phases of formalin-induced paw licking and increased reaction time of mice in the tail-immersion test.Conclusion:These findings suggest the total alkaloid extract from Linum usitatissimum seeds presents significant anti-inflammatory and analgesic effects on chemical behavioral models of inflammation and nociception in mice.
Identification of Pim-1 Kinase Inhibitors by Pharmacophore Model, Molecular
Docking-based Virtual Screening, and Biological Evaluation
Authors: Zhu Ying , Huang Jing , Yuan Ye , Zhu Xiaoxiao , Li Guodong , Xu Ya , Chen Wenlin 
Published: April 2022

Aim:
This study aimed at screening and development of Pim-1 inhibitors as anticancer agent.

Background:
Pim-1, a member of the Ser/Thr kinase family, plays a crucial role in cell prolifera-tion and is being regarded as a promising target for cancer therapeutics.

Objective:
The present work focused on screening more potent Pim-1 inhibitors by in-silico method and biological evaluation.

Materials and Methods:
To identify more potent Pim-1 inhibitors, a GALAHAD pharmacophore model was constructed based on nine known Pim-1 inhibitors and followed by in silico screening including pharmacophore and molecular docking-based virtual screening. The hit compounds were further assessed the Pim-1, 2, and 3 kinase activities and the anticancer inhibition property against human myeloma RPMI-8226 and U266 cells using cytotoxicity studies.

Results:
Based on Qfit value (from pharmacophore), docking score and clustering analysis, six compounds including C445_0268, C470_0769, 4456_0744, 0806_0325, G395_1510 and V023_3227 were hit. Binding mode analysis showed that hydrogen bond, hydrophobic and π-π stacking interactions dominated the bindings of these compounds to Pim-1. The further biological evaluation indicated that compounds C445_0268 and C470_0769 possessed excellent pan-Pim ki-nase activities and inhibited the growths of RPMI-8226 and U266 cell lines with IC50 values lower than 3.75 μM.

Conclusion:
We reported a series of Pim-1 small molecule inhibitors that could serve as the lead compounds to develop new targeted anticancer therapeutics.