bluuebunny/crossref_metadata_2025 huggingface dataset:
The return of RET GateKeeper mutations? An In-silico exploratory analysis of potential resistance mechanisms to novel RET macrocyclic inhibitor TPX-0046
Authors: Repetto Matteo , Crimini Edoardo , Ascione Liliana , Bielo Luca Boscolo , Belli Carmen , Curigliano Giuseppe
Published: February 2022

Purpose: TPX-0046 is designed to overcome resistance to FDA approved RET inhibitors Selpercatinib and Pralsetinib. Early prediction of resistance mechanisms to investigational drugs may facilitate subsequent drug and trial designs. This study aims to predict potential mutations inducing resistance to TPX-0046.Materials and methods: We conducted an in-silico analysis of TPX-0046 macrocyclic structure and predicted the binding mode on RET. We used as reference literary examples of resistance mechanisms to other macrocyclic inhibitors (Lorlatinib on ALK/ROS1) to construct RET secondary resistance mutations. We conducted docking simulations to evaluate impact of mutations on TPX-0046 binding.Results: TPX-0046 binding mode on RET appears to not be influenced by Solventfront G810X mutation presence. Bulky Gatekeeper V804X mutations affect predicted TPX-0046 binding mode. Mutations in Beta 7 strand region L881F and xDFG S891L impair TPX-0046 docking.Conclusions: Our findings suggest that development of second generation RET inhibitors focused mainly on Solventfront G810X mutations granting resistance to selective RET inhibitors Selpercatinib and Pralsetinib. If these findings are confirmed by identification of Gatekeeper V804X mutations in patients progressing to TPX-0046, explanation of acquired resistance and loss of benefit will be easier These findings might accelerate development of third generation RET inhibitors, as well as clinical trial design in precision oncology settings.
Triiodothyronine Treatment Reverses Depression-Like Behavior in a Triple-Transgenic Animal Model of Alzheimer’s Disease.
Authors: Maglione Andrea , Nascimento Bruna , Ribeiro Miriam , Souza Talytha , Silva Renata , Sato Monica , Penatti Carlos , Britto Luiz , Souza Janaina , Maciel Rui , Conceição Rodrigo Rodrigues da , Melo Roberto Laureano - , Giannocco Gisele
Published: February 2022

Introduction: Alzheimer disease’s (AD) is a neurodegenerative disorder and it is known that the central nervous system (CNS) is an important target of thyroid hormones (TH). Moreover, an inverse association between serum triiodothyronine (T3) levels and the risk of AD was reported. Aim: To evaluate the effects of T3 treatment on the depression-like behavior observed in male transgenic 3xTg-AD mice. Main methods: Animals were divided into 2 groups, one group received daily intraperitoneal injections of L-T3 (T3 group), and the other received an equivalent volume of 0.9% saline (Control group). The experimental protocol lasted 21 days, and behavioral tests were conducted on days 15-19. At the conclusion of the experiment, the TH profile and hippocampal gene expression were evaluated. Key findings: It was observed that the T3-treated group presented significantly increased serum T3 and decreased thyroxine (T4) levels. When compared to control hippocampal samples, the T3 group exhibited attenuated glycogen synthase kinase-3 (GSK3), metalloproteinase 10 (ADAM10), amyloid-beta precursor-protein (APP), serotonin transporter (SERT), 5HT1a receptor, monocarboxylate transporter 8 (MCT8) and bone morphogenetic protein 7 (BMP-7) gene expression levels and augmented superoxide dismutase 2 (SOD2) and Hairless gene expression levels. Additionally, T3-treated animals displayed reduced immobility time in both the tail suspension and forced swim tests, and in the latter presented a higher latency time when compared to the control group. Significance: Taken together, our results demonstrate that in an AD mouse model, T3 supplementation promotes improvements in depression-like behavior, likely through the modulation of the serotonergic pathway, and also attenuated disease progression.
Direct identification of interfacial degradation in blue phosphorescent OLEDs using nanoscale chemical depth profiling
Authors: Sul Soohwan , Trindade Gustavo , Kim Joonghyuk , Havelund Rasmus , Park Sungjun , Shin Youngsik , Bae Hyejin , Sung Young Mo , Matjacic Lidija , Jung Yongsik , Won Jung Yeon , Jeon Woo Sung , Choi Hyeonho , Lee Hyo Sug , Lee Jae-Cheol , Kim Jung-Hwa , Gilmore Ian
Published: February 2022

Understanding the degradation mechanism of organic light-emitting diodes (OLED) is essential to improve device performance and stability. OLED failure, if not process-related, arises mostly from chemical instability. However, the challenges of sampling from nanoscale organic layers and interfaces with enough analytical information has hampered identification of degradation products and mechanisms. Here, we present a high-resolution diagnostic method of OLED degradation using an Orbitrap mass spectrometer equipped with a gas cluster ion beam to gently desorb nanometre levels of materials, providing unambiguous molecular information with 7-nm depth resolution. We measured blue phosphorescent OLED devices and showed that dominant chemical degradation occurred at the interface between electron transport and emission layers (EML/ETL) where exciton distribution was maximised. We also show an approximately two orders of magnitude increase in lifetime of a device with slightly modified host material, which presented negligible EML/ETL interfacial degradation. Our results provide insight for material and device architecture development.
Autophagy Inhibits Renal Tubule Inflammation in Diabetic Kidney Disease Mice Via Inhibition of NLRP3 Inflammasome
Authors: Xinxin Pang , Zhang Ya-ge , Zhang Li-jie , Zhu Qing , Shang Hai-tao , Wang Zhen-tao
Published: February 2022

Background

Diabetic kidney disease (DKD) has become the leading cause of chronic kidney disease and numerous reports have validated that renal tubule inflammation participate in DKD progression. However, the molecular mechanism underlying renal tubular inflammatory damage in DKD remains to be completely elucidated. The aim of this study is to investigate the effect of rapamycin-induced autophagy on Nod-like receptor family protein 3 (NLRP3) inflammasome and inflammation of renal tubular epithelial cells in DKD.
Methods

We collected kidney tissue specimens from patients with DKD and transplanted kidney donors for histopathological examination and performed urine and blood samples. The STZ-induced DKD mice model was established for in vivo study. The mice were divided into three groups: Ctrl, DKD, DKD+Rapa. Collected the serum for 24 h protein quantification, blood glucose, C-peptide and insulin level investigations. PAS staining and electron microscopy were used to visualize the pathological changes in the kidney and the expressions of Beclin1, P62, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) protein, interleukin (IL)-1β, IL-18, β2-microglobulin (β2-MG); 24 urine protein, and creatinine in the kidney tissue were detected. Moreover, human renal proximal tubule cells (HK-2) were cultured in vitro, and high glucose was used to induce the model, followed by rapamycin treatment. The protein expression of Beclin1, P62, ASC protein, IL-1β, IL-18, 24 urine protein, and creatinine were analyzed.
Results

Compared with the model group mice, after rapamycin treatment, urinary protein decreased quantitatively, blood glucose decreased, C-peptide and insulin levels increased (P<0.01), glomerular basement membrane did not thicken obviously, and the expressions of P62, NLRP3, ASC protein, IL-1β and IL-18 protein in renal tissue decreased, while Beclin-1 level increased (P<0.05). After high glucose intervention in vitro, the expression of NLRP3, ASC protein, IL-1β and IL-18 protein in HK-2 cells increased, while the level of Beclin-1 decreased. The expression of NLRP3, ASC, IL-1β and IL-18 decreased and Beclin-1 level increased after rapamycin intervention (P<0.05).
Conclusion

The findings of the present study indicated that the NLRP3 inflammasomemediated inflammatory response was activated in DKD. Rapamycin can inhibit the activation of NLRP3 inflammasome in DKD by enhancing autophagy.
An Intrinsically Glassy Metallic Coordination Polymer Showing Thermally and Aerobically Robust Conductivity
Authors: Anderson John , Xie Jiaze , Ewing Simon , Boyn Jan-Niklas , Cheng Baorui , Filatov Alexander , Ma Tengzhou , Zhao Norman , Itani Ram , Sun Xiaotong , Cho Himchan , Patel Shrayesh , Talapin Dmitri , Park Jiwoong , Mazziotti David
Published: February 2022

Conducting organic materials, such as doped organic polymers, (1) molecular conductors, (2,3) and emerging coordination polymers, (4) underpin technologies ranging from displays to flexible electronics. (5) Realizing high electrical conductivity in traditionally insulating organic materials necessitates tuning their electronic structure through chemical doping. (6) Furthermore, even materials that are intrinsically conductive, such as single-component molecular conductors, (7,8) require crystallinity for metallic behavior. However, commercial conducting polymers are often purposefully amorphous to aid in durability and processability. (9,10) Using molecular design to engender high conductivity in undoped amorphous materials would enable tunable and robust conductivity in many applications, but there are no intrinsically conducting organic materials which maintain high conductivity when disordered. Here we show that the completely amorphous coordination polymer Ni tetrathiafulvalene tetrathiolate (NiTTFtt) displays intrinsic metallic conductivity. Despite its disordered structure, NiTTFtt exhibits remarkably high electronic conductivity (1280 S/cm) and intrinsically glassy metallic behavior. Analysis with advanced theory shows that these properties are enabled by strong molecular overlap and correlation that are robust to structural perturbations. This unusual set of structural and electronic features results in remarkably stable organic conductivity which is maintained in air for weeks and at temperatures up to 140 °C. Our results demonstrate that molecular design can enable metallic conductivity even in heavily disordered materials. This both raises fundamental questions about how band-like transport can exist in the absence of periodic structure as well as suggests exciting new applications for these materials.
EHR Implementation and Financial Performance: The Case of Under-Resourced (High Medicaid) Nursing Homes
Authors: Dayama Neeraj , Pradhan Rohit , Davlyatov Ganisher , Weech-Maldonado Robert
Published: February 2022

Background: The nursing home industry operates in a two-tiered system—high Medicaid nursing homes (Medicaid census > 85%) cater disproportionately to marginalized populations, and exhibit both poorer quality of care and financial performance. Despite EHRs’ purported positive impact on nursing home performance, high Medicaid nursing homes may be precluded from implementing EHR due to their precarious financial position. Compelling evidence on a return on investment (ROI) from HIT adoption may be required for reluctant nursing homes to invest in HIT systems. Utilizing the Resource-Based View (RBV), the primary purpose of this study was to understand whether EHR implementation in high Medicaid nursing homes is associated with improved financial performance. Methods: EHR implementation data in high Medicaid nursing homes was collected via mail surveys sent to the Directors of Nursing (DON). We surveyed 1050 high Medicaid nursing homes and received 391 responses. The survey data was merged with the following secondary data sources: Brown University’s LTCFocus, Area Health Resource File (AHRF), and the CMS Medicare Cost Reports. Multivariable regression model was used to understand the effect of EHR implementation on financial performance (total margin), adjusting for both organizational and market-level variables and potential non-response bias using propensity score inverse probability weighting. Results: Approximately 76% of nursing homes in our study sample had either fully or partially implemented EHR. In our multivariable regression model, for every unit increase in total(average) EHR implementation, there was a 3.12% increase in the total margin (p<0.05). Conclusions: High Medicaid nursing homes with higher EHR implementation experienced superior financial performance. Improved financial performance may result from increased revenues and/or reduced costs via the ability to attract more remunerative residents, greater charge capture, improved practice efficiency, documentation management, medication safety, and adverse event reporting.Implications for Policy or Practice: From a policy standpoint, our findings suggesting a sustainable economic argument for EHR implementation offer a strong rationale for targeted policy efforts, including extending subsidies, to ensure that US nursing homes are no longer the laggards in EHR implementation. For nursing home administrators, our findings suggest a potential business case—there may be long-term financial returns for the initial financial burden of EHR implementation.
Afforestation alters functions of soil and microbiome but does not drive soil carbon accumulation in two decades
Authors: Qi Wenhua , Zhang Quanfa , Chen Youchao , Li Xinshuai , Cheng Xiaoli , Ye Chen , Lu Fei , Dang Haishan , Zhang Kerong
Published: February 2022

Afforestation has been proposed as an effective strategy for restoration and carbon sequestration, however, its impacts on the functions of soils and microbiome remain poorly understood. By analyzing 144 afforestation sites across a 159 000 square kilometer watershed in China, a typical region characterized with rapid forest expansion in global land-use change map, we provided the first large-scale observation evidence that afforestation did not drive net accumulation of soil carbon and nitrogen in two decades. Afforestation significantly shifted the soil microbial community and their functional profiles of element cycling, increased soil prokaryotic diversity but reduced fungal diversity. Afforestation reduced the network complexity of soil prokaryotes but did not change the complexity of fungal networks. Planting introduced- poplar reduced soil multifunctionality while native trees did not change multifunctionality. Our results reveal the ecological responses of soils to afforestation across a broad geographic scale and provide new insights for forest restoration programs.
Network pharmacology and bioinformatics approach reveals the therapeutic mechanism of action of curcumin in Alzheimer disease
Authors: Vijh Deepanshi , Imam Md. Ali , Haque Mohd Maksuf Ul , Das Subhajit , Islam Asimul , Malik Md Zubbair
Published: February 2022

Curcumin possesses antioxidant and anti-inflammatory properties and shows a major role in reducing the amyloid plaques formation which is the major cause of Alzheimer’s disease (AD). Consequently, a methodical approach was used to select the potential protein targets of curcumin in AD through network pharmacology. In this study, through integrative methods AD targets of curcumin through SwissTargetPrediction databases, STITCH database, BindingDB, PharmMapper, Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM) database were predicted followed by gene enrichment, network construction, network topology, and docking studies. Gene ontology analysis facilitated identification of a list of possible AD targets of curcumin (74 targets genes). The correlation of the obtained targets with AD was analysed by Gene Ontology (GO) pathway enrichment analyses and Kyoto Encyclopaedia of Genes and Genomes (KEGG). Using network pharmacological approach, we identified five key genes (RARA, APP, PRARG, STAT3 and MAPK1). Further, we performed molecular docking for analysing the mechanism of curcumin. To validate the temporospatial expression of key genes in human central nervous system (CNS), we searched the Human Brain Transcriptome (HBT) dataset. This study concluded with novel insights into the therapeutic mechanisms of curcumin which in the future will ease the treatment of AD with the clinical application of curcumin.
Microvesicle-camouflaged biomimetic nanoparticles encapsulating a metal-organic framework for targeted rheumatoid arthritis therapy
Authors: Wang Yao , Jia Ming , Zheng Xiu , Wang Chenglong , Zhou Yun , Pan Hong , Liu Yan , Lu Ji , Mei Zhiqiang , Li Chunhong
Published: February 2022

Background: Methotrexate (MTX) has been highlighted for Rheumatoid arthritis (RA) treatment, however, MTX does not accumulate well at inflamed sites, and long-term administration in high doses leads to severe side effects. In this study, a novel anti-RA nanoparticle complex was designed and constructed, which could improve the targeted accumulation in inflamed joints and reduce side effects.Results: Here, we prepared a pH-sensitive biomimetic drug delivery system based on macrophage-derived microvesicle (MV)-coated zeolitic imidazolate framework-8 nanoparticles that encapsulated the drug methotrexate (hereafter MV/MTX@ZIF-8). The MV/MTX@ZIF-8 nanoparticles were further modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate (polyethylene glycol)-2000] (hereafter FPD/MV/MTX@ZIF-8) to exploit the high affinity of folate receptor β for folic acid on the surface of activated macrophages in RA. MTX@ZIF-8 nanoparticles showed high DLE (~70%) and EE (~82%). In vitro study showed that effective drug release in an acidic environment could be achieved. Further, we confirmed the activated macrophage could uptake much more FPD/MV/MTX@ZIF-8 than inactivated cells. In vivo biodistribution experiment displayed FPD/MV/MTX@ZIF-8 nanoparticles showed the longest circulation time and best joint targeting. Furthermore, pharmacodynamic experiments confirmed that FPD/MV/MTX@ZIF-8 showed sufficient therapeutic efficacy and safety to explore clinical applications.Conclusion: This study provides a novel approach for the development of biocompatible drug-encapsulating nanomaterials based on MV-coated metal-organic frameworks for effective RA treatment.
Synthesis, Characterization and Biological Evaluation of Bis-benzimidazolium Salts and Their Silver(I)-N-Heterocyclic Carbene Complexes
Authors: Iqbal Muhammad Adnan , Nadeem Rana Yasir , Yaqoob Munazzah , Yam WanSinn , Haque Rosenani A.
Published: February 2022

Azolium salts are stable sources of N-heterocyclic carbenes (NHCs), an emerging class of ligands. Due to prominent properties, they have versatile applications. In the current study, new bis-benzimidazolium salts and their silver complexes were synthesized and confirmed through spectroscopic analysis. Compounds were characterized using FT-IR, 1H NMR, and 13C NMR spectroscopies. Biological potentials of these compounds were investigated for antibacterial activity against both the gram-positive (Staphylococcus Aureus) and gram-negative (Escherichia Coli) strains. The salts L1 and L2 showed zone inhibition of 17 ± 1 and 13.33 ± 0.58 mm for S. Aureus and 8.83 ± 0.76 and 8.83 ± 0.58 mm for E. Coli, respectively. The respective silver complexes C1 and C2 showed better zone of inhibitions for both the strains, i.e., 18.67 ± 0.58 and 19.83 ± 0.29 mm for S. Aureus and 12.5 ± 0.5 and 14.33 ± 0.58 mm for E. Coli, respectively. The salts showed a good trend in scavenging concerning the increasing concentration and presented the IC50 values in the range of 3.51 and 15.36 µg/mL, respectively, which showed that these compounds are good antioxidant agents. The Hemolytic potentential of compounds were checked and L2 was found least tixic with 7.37 ± 0.11 value.
Dynamics in COVID-19 Symptoms During Different Waves of the Pandemic Among Children Infected with SARS-CoV-2
Authors: Tov Amir Ben , Lotan Roni , Gazit Sivan , Chodick Gabriel , Perez Galit , Mizrahi-Reuveni Miri , Patalon tal
Published: February 2022

The aim of this real-life, big data population-based study was to evaluate differences in symptomatic presentation of children infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) between the third and fourth waves of the pandemic in Israel, dominated by the Alpha and Delta variants, respectively. Our cohort included all children and adolescents, members of the second-largest Health Maintenance Organisation in Israel that had positive real-time polymerase chain reaction (RT-PCR) test during the third and fourth waves of the pandemic (December 1, 2020 - April 30, 2021, and June 1, 2021 - October 10, 2021, respectively). A total of 32,485 and 44,130 children and adolescents in the third and fourth waves were included in the final analysis. The rate of children with symptomatic disease among patients with documented SARS-CoV-2 infection was higher in the fourth wave compared to the third wave (49.9% vs. 37.5%). The most commonly reported symptom and the only symptom that substantially differed between waves was fever, with 33% of SARS-CoV-2 infected children in the fourth wave vs. 13.6% in the third wave. Preschool children had the lowest prevalence of febrile illness compared to other age groups.Conclusion: Children and adolescents infected during the fourth wave of the pandemic in Israel, a Delta-dominant period, had a significantly higher rate of symptomatic febrile illness than the Alpha-dominant period. This phenomenon occurred across all age groups.
Biotechnologies Tools for Germination and Preservation of Butia Eriospatha Embryos (Arecaceae)
Authors: Daniela Goeten , Elias Rosa Angélica , Silva Maycon Moraes da , Walters Christina , Guerra Miguel Pedro , Steiner Neusa
Published: February 2022

Butia eriospatha is an endemic species of Brazilian Atlantic Forest and due to the anthropic intervention, it is in the vulnerable conservation status. In this species, plants are only regenerate by seeds which have dormancy and slow as well low germination. To cope with the concern limitation of seedling establishment we study B. eriospatha embryo desiccation tolerance threshold as well the physiological requirement for in vitro germination and cryopreservation. Fresh embryos and desiccated ones were in vitro germinated using a culture medium with hormones and antioxidants. The embryo desiccation tolerance threshold was 0.14 gH2O.gDW-1 with 93.33% of germination. During embryos desiccation was observed a significant increase in PUT, which resulted in the ratio decrease [(SPD+SPM). PUT-1] DW), but the SPD was the most abundant polyamine overall. Significant increase in POD and APX activity led us to suggest that they are the main enzymes involved in cellular protection during desiccation. An increase of amino acids content, especially glutamic acid (Glu), leucine (Leu), lysine (Lys), glutamine (Gln), which are known as osmoprotectors, also was observed. A specific embryo desiccation stage (0.14 gH2O gDW-1) associated to its biochemical state were successfully used in the cryopreservation protocol and result in more than 90% of recovery and in vitro germination. The physiological and biochemistry approach of this study associated to an applied protocol for plant genetic resources conservation of B. eriospatha embryo can be potentially used for other Arecaceae species.
Synthesis, Thermal properties and electrical conductivity of Na-Sialate geopolymer
Authors: SOUISSI Fatma Zahra , Hajji Malek , Ettoumi Houda , Sellami Mouna , BenKhalifa Jamel , Barre Maud , Guerfel Taha
Published: February 2022

In this work, the central focus is upon the synthesis of new Na-Sialate geopolymer concerning as ionic conductive material for electric and electrochemical devices. The studied material was prepared at ambient temperature by a mixture of metakaolin and sodium hydroxide. In order to study the change in gel structure and phase composition at each heating step. The synthetic compound was characterized by several techniques.The phase identification of Na-Sialate geopolymer, was carried out by powders X-ray diffraction, showed an amorphous character at ambient temperature. As well as minor amounts of high temperature crystalline phases were appeared which were: zeolite (300-600°C), Nepheline (NaAlSiO4) (900-1150° C). Above 1200°C, the structural reorganization occurs due to the phase crystallization of corundum (α-Al2O3). The dissolution of the grains by the liquid phase formed induces the conversion of the structure of the material from sialate [-Si-O-Al-O] to sialate siloxo [-Si-O-Al-O-Si-O-]. These results were confirmed by Fourier transform infrared spectroscopy (FT-IR).The thermal analysis offered a thermal stability of Na-geopolymer up to 1400°C.The electrical measurements were applied to investigate Na+ ions conductivity of Na-geopolymer. The results showed that Na-Sialate geopolymer materials exhibit high ionic conductivity of approximately 5.10−5 S.cm− 1 in air, at room temperature.
Attachment Styles And Happiness In The Elderly: The Mediating Role of Reminiscence Styles
Authors: Momeni Khodamorad , Amani Rozita , Janjani Parisa , Majzoobi Mohammad Reza , Forstmeier Simon , Nosrati Parisa
Published: February 2022

Background: The current study aims to investigate the relationship between attachment styles and happiness through the mediating role of reminiscence styles in the elderly. Methods: This was a correlational study of structural equations modelling (SEM) type. The statistical population included all the elderly aged at least 60 years living in Kermanshah province, Iran in 2021, among whom 380 (182 men and 198 women) were selected using convenience sampling method. Participants filled out the questionnaires of Adult Attachment Styles, Oxford Happiness, and Amani et al.’s Reminiscence Styles. Results: The results indicated that secure attachment style has a positive and negative relationship with positive reminiscence (PR) and negative reminiscence (NR), respectively. However, the opposite held true for both avoidant and ambivalent attachment styles. It was also found that secure attachment style has a positive relationship, and avoidant and ambivalent attachment styles have a negative relationship with happiness. Moreover, participants’ gender and age had no moderating effect on the mentioned relationships. The results of SEM indicated that secure and ambivalent attachment styles were associated with happiness through both PR and NR, and avoidant attachment style was associated with happiness only through NR. Conclusions: The findings emphasize the significance of the development of internal working models based on the kind of parent-child’s reminiscences and narratives, and the lifelong effects of these models.
Lipid-Coated Hybrid Nanoparticles for Enhanced Bacterial Biofilm Penetration and Antibiofilm Efficacy
Authors: Lee Hiang Wee , Kharel Sharad , Loo Say Chye Joachim
Published: February 2022

Background: The biofilm way of life is a common strategy for bacteria to adapt and gain tolerance towards antibiotic treatments. Up to 80% of all infections are biofilm-mediated and they are often challenging to treat as the underlying bacterial cells can become 100 – 1000-fold more tolerant towards antibiotics. Antibiotic-loaded nanoparticles have gained traction as a potential drug delivery system to treat biofilm infections. Specifically, lipid-coated hybrid nanoparticles (LCHNPs) were investigated on their capability to deliver antibiotics into biofilms. In this study, LCHNPs composed of a poly(lactic-co-glycolic acid) (PLGA) core and dioleoyl-3-trimethylammonium propane (DOTAP) lipid shell were developed and loaded with vancomycin (Van). In vitro antibacterial and antibiofilm tests were performed to evaluate the antimicrobial efficacy of the LCHNPs. Results: LCHNPs were successfully fabricated with high vancomycin encapsulation efficiency of 48.66% and loading efficiency of 72.99 µg/mg. DOTAP was determined to be successfully coated on the PLGA core by measuring the ζ-potential of the nanoparticles. LCHNPs had a positive ζ-potential of +36.13 mV which contrasted significantly from the ζ-potential of -36.83 mV of bare PLGA nanoparticles (PLGANPs). LCHNPs exhibited enhanced antibacterial effects against planktonic Staphylococcus aureus USA300 cells, with at least 6-fold reduction in minimum inhibitory concentration when compared against Free-Van and Van-PLGANPs. When used to treat USA300 biofilms, Van-LCHNPs eradicated up to 99.99% of the underlying biofilm cells, an effect which was not observed for Free-Van and Van-PLGANPs. Finally, we showed that by possessing a robust DOTAP shell, LCHNPs were able to penetrate deeply into the biofilms. Conclusion: LCHNPs were shown to display remarkable antimicrobial efficacy towards both planktonic and biofilm cells as the presence of the lipid shell enhanced the interactions with bacterial cells and penetration into biofilms. More work could be done to understand nanoparticle-biofilm interactions; this would help to optimize the LCHNPs further to treat biofilm infections successfully.
Green Synthesis of Iron Oxide Nanoparticles Using Ceratonia Siliqua L. Aqueous Extract: Optimization, Characterization, Stabilization and Evaluation of Its Antibacterial Activity Against Gram-Positive and Gram-Negative Bacteria
Authors: Demirezen Derya Aksu , Yılmaz Şeyda , Yılmaz Dilek Demirezen , Yıldız Yalçın Şevki
Published: February 2022

This study focused on the optimization of reaction parameters for a simple and reliable method for the green synthesis of iron oxide nanoparticles (gIONPs). The potential of aqueous extract of the Ceratonia siliqua L. (carob pod) as a reducing, capping, and stabilizing agent for gIONPs synthesis, and the antibacterial activity of as-synthesized gIONPs was investigated. The synthesis parameters were determined as the concentration of iron ion, the concentration of extract, pH of extract, temperature, stirring rate, and reaction time. The significance of the studied factors in controlling the particle size distribution of nanoparticles was quantitatively evaluated via analysis of variance (ANOVA). Iron oxide nanoparticles were produced at the optimum parameters with an average zeta potential of + 40.75 ± 1.22 mV, hydrodynamic size of 78 ± 22 nm, and a polydispersity value of 0.42 ± 0.06, respectively. gIONPs showed the highest inhibition zones of 24 mm and 21 mm in 250 mg/mL concentration against Gram-negative Escherichia Coli and Gram-positive Staphylococcus aureus, respectively. Strong antibacterial activity was observed when compared with the standard antibiotics. The findings of the study revealed that the highly stable and antibacterial iron oxide nanoparticles can be synthesized through the adjustment of the reaction parameters by eliminating chemicals and increasing awareness of green chemistry.
Characteristics of Gut Microbiota and Its Relationship With Serum Sex Hormones in Non-obese Polycystic Ovary Syndrome Patients With Insulin Resistance
Authors: Cai Mengcheng , Ni Zhexin , Yao YanNing , Yu Jin , Yu Chaoqin , Zhou Ling , Zhai Dongxia
Published: February 2022

Background: Insulin resistance (IR) is a common symptom in obese polycystic ovary syndrome (PCOS) patients, as well as in non-obese PCOS patients. Gut microbiota is closely related to IR. However, the relationship between gut microbiota and IR remains unclear in non-obese PCOS patients. Objective: To analyze the composition of the gut microbiota population in non-obese PCOS-IR patients compared to PCOS alone and healthy women. Methods: In the present study, fecal samples from non-obese PCOS patients with and without IR and healthy women were analyzed by 16S rRNA gene sequencing. Moreover, serum hormone levels were detected on the third day of menstruation, and the correlation between gut microbiota and serum hormone was analyzed using R language.Results: We found that the gut microbiota character differed in each group, and the gut microbiota abundance of PCOS-IR group was remarkably reduced.The abundance of Ruminococcaceae_UCG-004 and Acetanaerobacterium in the PCOS-IR group was significantly lower than that of the PCOS-NIR group. Furthermore, the comparison between PCOS-IR and control group revealed that g__Fusobacterium and g__Faecalibaculum were the unique genus of the PCOS-IR group. Moreover, the relationship between gut microbiota, IR, and serum sex hormones was determined. In PCOS with IR group, the relationship between gut microbiota and androgen was more significant. In PCOS without IR group, the relationship between gut microbiota and androgen was no significant. Its mechanism may be related to the different abundance in enzymes (futalosine hydrolase, arogenate dehydrogenase (NADP(+), and L-lysine 6-transaminase) and metabolic pathways (isoquinoline alkaloid biosynthesis, styrene degradation, and atrazine degradation), but it needs to be further explored in subsequent experiments. Conclusion: The gut microbiota composition of non-obese PCOS patients with insulin resistance is different from that of PCOS alone and healthy women. The difference is correlated with the clinical characteristics of PCOS, with regards to insulin resistance and sex hormone. The abnormality of gut microbiota may lead to the occurrence and development of PCOS-IR. All in all, this study not only provided supplements for the existing studies, but also revealed the potential pathogenic bacteria genus, thus providing a new idea for the treatment of PCOS with IR.
Expectation Maximization Algorithm with Combinatorial Assumption
Authors: Nguyen Loc
Published: February 2022

Expectation maximization (EM) algorithm is a popular and powerful mathematical method for parameter estimation in case that there exist both observed data and hidden data. The EM process depends on an implicit relationship between observed data and hidden data which is specified by a mapping function in traditional EM and a joint probability density function (PDF) in practical EM. However, the mapping function is vague and impractical whereas the joint PDF is not easy to be defined because of heterogeneity between observed data and hidden data. The research aims to improve competency of EM by making it more feasible and easier to be specified, which removes the vagueness. Therefore, the research proposes an assumption that observed data is the combination of hidden data which is realized as an analytic function where data points are numerical. In other words, observed points are supposedly calculated from hidden points via regression model. Mathematical computations and proofs indicate feasibility and clearness of the proposed method which can be considered as an extension of EM.
Ptpn20 Deletion in H-tx Rats Facilitates Cotransporter-mediated Water Transport in the Choroid Plexus: Evidence of Genetic Risk for Hydrocephalus in an Experimental Study
Authors: Xu Hanbing , Miyajima Masakazu , Nakajima Madoka , Ogino Ikuko , Kawamura Kaito , Akiba Chihiro , Kamohara Chihiro , Sakamoto Koichiro , Karagiozov Kostadin , Nakamura Eri , Tada Nobuhiro , Arai Hajime , Kondo Akihide
Published: February 2022

BackgroundCongenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus.MethodsComparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus. ResultsCGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats, encompassing the Ptpn20 gene, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20-/-) mice were generated and found to develop ventriculomegaly. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20. ConclusionsThe high level of pNKCC1 in CP epithelium may cause the overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20-/- mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.
Movements of Free-Range Pigs in Rural Communities in Zambia: An Explorative Study Towards Future Ring Interventions for the Control of Taenia Solium
Authors: Damme Inge Van , Pray Ian , Mwape Kabemba E. , Trevisan Chiara , Coudenys Fien , Mubanga Chishimba , Mwelwa Chembesofu , Vaernewyck Victor , Dorny Pierre , O’Neal Seth E. , Gabriël Sarah
Published: February 2022

Background: Taenia solium typically affects resource-poor communities where pigs are allowed to roam freely, and sanitation and hygiene levels are suboptimal. Sustainable, long-term strategies are urgently needed to control the disease. Geographically targeted interventions, i.e., screening or treatment of taeniosis among people living near infected pigs (defined as ring screening and ring treatment, respectively), have been shown to be effective control options in Peru. However, these results might not be directly generalizable to sub-Saharan African settings. Pig movements play a vital role in the transmission and consequently the success of ring interventions against T. solium. Therefore, the aim of the present study was to explore roaming patterns of pigs in T. solium endemic communities in Zambia as a first step to evaluate whether ring interventions should be considered in Zambia. Methods: In total, 48 free-roaming pigs in two rural neighborhoods in Eastern Province of Zambia were tracked using a Global Positioning System (GPS) receiver. Tracking took place in April 2019 (end of the rainy season) and October 2019 (end of the dry season). The number of revisitations and the time spent within rings of different radii (50m, 100m, and 250m) around the coordinates of the pig owners’ household were calculated for each pig. Results: The tracking time of 43 pigs in the final analysis set ranged between 43 and 94 hours. Pigs spent a median of 31% and 13% of the tracked time outside the 50m and 100m radius, respectively, though large variations were observed between pigs. Overall, 25 pigs (58%) went outside the 250m ring at least once, and individual visits up to 16 hours were observed. In the dry season, 17 out of 23 pigs went outside the 250m radius compared to only 8 out of 20 pigs in the rainy season (p = 0.014).Conclusions: In our study sites in Zambia, the majority of pigs spent most of their time within 50 or 100 m of their owners’ home, and results are comparable with those of Peruvian pigs. Both radii could therefore be considered reasonable in future ring interventions.
Association between triglycerides to high-density lipoprotein cholesterol ratio and death risk in diabetic patients with new-onset acute coronary syndrome：a retrospective cohort study in Han Chinese population
Authors: Cong Hongliang , Shi Dongdong , Wang Le
Published: February 2022

Background and Aims: The incidence of diabetes mellitus has reached an alarming level. Cardiovascular disease (CVD) is the leading cause of mortality in diabetic patients. However, the association between ratio and survival outcomes in patients with diabetes mellitus (DM) and new-onset acute coronary syndrome (ACS) remains unknown. The study aimed to assess the association between TG/HDLC ratio and the death risk in diabetic patients with new-onset acute coronary syndrome in Han Chinese population. Methods: Data in this study were retrospectively collected from January 2016 to December 2016 from patients with type 2 diabetes mellitus(T2DM) and new-onset ACS in Tianjin Chest Hospital. Patients were classified according to the baseline TG/HDLC ratio. The Kaplan-Meier survival curve showed survival outcomes. Univariate and multivariate Cox proportional risk regression analyses were used to evaluate the hazard ratios and 95% confidence intervals (CIs) of death risk. Subgroup analysis was used to determine whether there was an interaction.Results: In total, 152 patients died, 98 of them from heart disease. The Kaplan-Meier survival curve showed that the group with a high TG/HDLC ratio has a higher mortality rate than the group with a low TG/HDLC ratio. Multivariate Cox regression analyses revealed that the adjusted hazard ratio increased significantly with increasing TG/HDLC median (P <0.05) for all-cause mortality and cardiac death. The association between TG/HDLC ratio and the risks of all-cause mortality and cardiac death in diabetic patients with new-onset ACS was similar among subgroups (P for interaction>0.05).Conclusion: Increased TG/HDLC ratio is significantly associated with higher all-cause and cardiac death risks in diabetic patients with new-onset ACS. Therefore, TG/HDLC ratio may be beneficial to evaluate the prognosis of this high-risk population.
A Balanced Butterfly Optimization Algorithm For Numerical Optimization And Feature Selection
Authors: Long Wen , Jiao Jianjun , Wu Tiebin , Xu Ming , Cai Shaohong
Published: February 2022

Butterfly optimization algorithm (BOA) is a relatively novel optimization technique for solving function optimization as well as real world applications. However, the paramount challenge in BOA is that it is prone to stagnation in local optima. The purpose of this study is to balance the exploration and exploitation abilities of BOA when two new strategies are introduced. The dynamic inertia weight based on Logistic model as the first strategy is introduced to modify the position updating equation. Another strategy is the opposition-based learning. A new variant of BOA called BBOA based on these two strategies is proposed. Ten widely used benchmark test functions and 30 complex benchmarks from CEC 2014 are selected to verify the effectiveness of BBOA. The used benchmark problems are composed of unimodal, multimodal, rotated, shifted, hybrid and composite functions. The experimental results and analysis show that the proposed BBOA has better exploration ability than the conventional BOA when solving different characteristics functions. Finally, BBOA is applied to solve three real-world engineering applications and sixteen feature selection problems. The results demonstrate that BBOA can outperform other competitors in terms of the accuracy of solution on constrained engineering design and feature selection problems.
Transplant-associated thrombotic microangiopathy and acquired nephrotic syndrome: A case report in a 35-month child.
Authors: Jose-Andres Tascon A. , Echeverri Catalina Velez , Garcia Carolina-Lucia Ochoa , F Arias. Luis , Jose Vanegas R. Juan
Published: February 2022

Background

Transplant-associated thrombotic microangiopathy (TA-TMA) presents with thrombocytopenia, nonimmune hemolytic anemia, peripheral blood schistocytes and end-organ damage to the kidney. TA-TMA is associated with a significant increased morbidity and mortality, especially when treatment is not initiated early. We present a pediatric clinical case of a 35-month child with history of hepatic transplantation, who develop the clinical spectrum of TA-TMA and acquired nephrotic syndrome.
Case presentation:

A 35-month-old boy with history of hepatic transplantation secondary of atresia of biliary ducts who received immunosuppressive therapy with tacrolimus, mycophenolate and steroids. He presents with 4 days of fever, vomiting, and non-dysenteric diarrhea. He received an initial course of antibiotics without response. After 3 days he continues with fever, low urine output and edema. Vital signs showed high blood pressure and physical exam revealed facial and extremity edema. Laboratory results showed proteinuria and hematuria, low albumin, and high triglycerides. All possible etiologies of nephrotic syndrome were ruled out. Kidney biopsy showed TMA changes. Plasma exchange and Eculizumab were started with clinical improvement.
Discussion

TMA can be classified as a primary or secondary. Primary TMA can be hereditary or acquired. Acquired TMA included the ones triggered by medications. This clinical syndrome has been described as an endothelial dysfunction secondary of an immune reaction over the endothelium and/or a direct cytotoxic effect over endothelium and platelets. In this case report the use of calcineurin inhibitors (tacrolimus) one of the most common drugs associated with TMA was one the triggers factors. Recent publications have described how these patients that are exposed to any triggers has also a genetically predisposing to develop TMA. There is a lack in diagnostics and prognostic markers. The earliest treatment is stared, the better prognosis and outcomes.
Characterization of transposable elements within the Bemisia tabaci species complex
Authors: Sicat Juan Paolo A. , Muhindira Paul Visendi , Sewe Steven O , Bouvaine Sophie , Seal Susan E
Published: February 2022

Background Whiteflies are agricultural pests that have caused worldwide negative impacts that have led to severe financial losses. The Bemisia tabaci whitefly species complex is the most damaging in terms of their broad crop host range and its ability to serve as vector for over 300 plant viruses. Whitefly genomes of the species complex provide valuable genomic data; however, transposable elements (TEs) within the species complex remain unexplored. This study provides the first accurate exploration of TE content within the B. tabaci species complex.Results This study identified an average of 40.61% of the genomes of three whitefly species (MEAM1, MEDQ, and SSA-ECA) consists of TEs. Majority of the TEs identified were DNA transposons (22.85% average) while SINEs (0.14% average) were the least represented. This study also compared the TE content the three whitefly genomes with three other hemipteran genomes and found a significant difference in the presence of DNA transposons and LINEs. A total of 63 TE superfamilies were identified to be present across the three whitefly species (39 DNA transposons, six LTR, 16 LINE, and two SINE) of which 11 TE superfamilies were identified to not be present in the three other hemipteran genomes (nine DNA transposon, and two LINE). This study is the first to characterize TEs found within different B. tabaci species and has created a standardized annotation workflow that could be used to analyze future whitefly genomes.Conclusion This study is the first to characterize the landscape of TEs within the B. tabaci species complex. The characterization of these elements within the three whitefly genomes shows that TEs occupy a significant portion of the whitefly genome, majority of which are DNA transposons. This study also identified TE superfamilies of note and provides a framework for future TE studies within the species complex.