bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of needs-based triggers for palliative care for early referral of older people with non-cancer conditions
Authors: Kawashima Arisa , Evans Catherine
Published: May 2022

Background: Older people with non-cancer disease are less likely to be referred to palliative care services due to the inherent uncertain disease trajectory and a lack of standardised referral criteria. For older people with non-cancer conditions where prognostic estimation is unpredictable, needs-based criteria are likely more suitable. Eligibility criteria for participation in clinical trials on palliative care could inform a needs-based criteria. This review aimed to identify and synthesise eligibility criteria for trials in palliative care to construct a needs-based set of triggers for timely referral to palliative care for older people severely affected by non-cancer conditions.Methods: Systematic review. Data sources were Medline, Embase, CINAHL, PsycINFO, CENTRAL, and ClinicalTrials.gov. were searched in September 2018 as well as hand searches. We included randomised controlled trials, including cluster randomised, pilot, and feasibility trials. We selected studies that reported the set of triggers for palliative care involvement for older people with non-cancer conditions, where >50% of the population was aged >65 years. The methodological quality of the included studies was assessed using the Cochrane Collaboration's tool for assessing risk of bias.Results: 16 randomised controlled trials out of 6,732 papers were identified. We identified six major domains of trial eligibility criteria in three categories, time-based, needs-based, and medical history-based criteria. Needs-based criteria were composed of symptoms, functional status, and quality of life criteria. The major trial eligibility criteria were diagnostic criteria (n = 15 [94%]), followed by physical and psychological symptoms, medical history-based criteria, respectively (n = 9 [56%]). Conclusion: For older people with non-cancer conditions, decisions about providing palliative care should be based on the present needs related to symptoms, functional status, and quality of life. Future research should investigate if the set of needs-based criteria can be used in clinical care to identify older people with non-cancer conditions likely to benefit from palliative care and acceptability of the referral criteria for older adults and their families.
The co-optimization method of tool parameters and mounting position parameters for cylindrical gears chamfering tool
Authors: He Kun , He Xiaohu , Du Yanbin , Wang Aoting , Yang Xiao
Published: May 2022

In the process of hobbing motion chamfering of cylindrical gear tooth profiles, the tool parameters and mounting position parameters of the chamfering tool directly affect the final chamfering result. Aiming at the multi-objective optimization requirements of tool parameters and mounting position parameters of the chamfering tools, a co-optimization method of multi-parameters based on Improved Non-dominated Sorting Genetic Algorithms-II (INSGA-II) is proposed. Firstly, considering the consistency and symmetry of chamfering result, the co-optimization model of multi-parameters is established with the minimum variance of chamfering width and thickness as the objectives, and the tool parameters and mounting position parameters as variables. Secondly, to avoid the tool parameters and mounting position parameters falling into local optimum, the normal distribution crossover operator is introduced in Non-dominated Sorting Genetic Algorithms-II (NSGA-II) to improve the searchability, and INSGA-II and Fuzzy C-means_Grey Relational Projection (FCM_GRP) are used to optimize and decision parameter combination. Finally, to further verify the applicability of the proposed co-optimization method, the optimized parameter combination is used to calculate the tool rake face profile, and the local curve superposition is used to improve the uneven chamfering at the transition arc. Based on the simulation of tooth profile chamfering, the simulation results verify the effectiveness of the proposed method.
Genetic dissection of morphological variation in rosette leaves and leafy heads in cabbage (Brassica oleracea var. capitata).
Authors: Alemán-Báez Jorge , Qin Jian , Cai Chengcheng , Zou Chunmei , Bucher Johan , Paulo Maria-João , Voorrips Roeland E. , Bonnema Guusje
Published: May 2022

Cabbage (B. oleracea var. capitata) is an economically important vegetable crop cultivated worldwide. Cabbage plants go through four vegetative stages: seedling, rosette, folding and heading. Rosette leaves are the largest leaves of cabbage plants and provide most of the energy needed to produce the leafy head. To understand the relationship and the genetic basis of leaf development and leafy head formation, 308 cabbage accessions were scored for rosette leaf and head traits in three-year field trials. Significant correlations were found between morphological traits of rosette leaves and heads, namely leaf area with the head area, height and width, and leaf width with the head area and head height, when heads were harvested at a fixed number of days after sowing. Fifty robust quantitative trait loci (QTLs) for rosette leaf and head traits distributed over all nine chromosomes were identified with genome-wide association studies (GWAS). All these 50 loci were identified in multiple years and generally affect multiple traits. Twenty-five of the QTL were associated with both rosette leaf and leafy head traits. We discuss sixteen candidate genes identified in these QTL with an annotation related to auxin and other phytohormones, leaf development, and leaf polarity that likely play a role in leafy head development or rosette leaf expansion.
MiRNA Sequencing of Embryonic Myogenesis in Chengkou Mountain Chicken
Authors: Shi Jun’an , Li Wendong , Liu Anfang , Ren Lingtong , Zhang Pusen , Jiang Ting , Han Yuqing , Liu Lingbin
Published: May 2022

Background: Skeletal muscle tissue is among the largest organ systems in mammals, essential for survival and movement. Embryonic muscle development determines the quantity and quality of muscles after the birth of an individual. MicroRNAs (miRNAs) are a significant class of non-coding RNAs that bind to the 3'UTR region of mRNA to regulate gene function. Total RNA was extracted from the leg muscles of chicken embryos in different developmental stages of Chengkou Mountain Chicken and used to generate 171,407,341 clean small RNA reads. Target prediction, GO, and KEGG enrichment analyses determined the significantly enriched genes and pathways. Differential analysis determined the significantly different miRNAs between chicken embryo leg muscles at different developmental stages. Meanwhile, the weighted correlation network analysis (WGCNA) identified key modules in different developmental stages, and the hub miRNAs were screened following the KME value.Results: The clean reads contained 2047 miRNAs, including 721 existing miRNAs, 1059 known miRNAs, and 267 novel miRNAs. Many genes and pathways related to muscle development were identified, including ERBB4, MEF2C, FZD4, the Wnt, Notch, and MAPK signaling pathways. The WGCNA established the greenyellow module and gga-miR-130b-5p for E12, magenta module and gga-miR-1643-5p for E16, purple module and gga-miR-12218-5p for E19, cyan module and gga-miR-132b-5p for E21. Conclusion: These results lay a foundation for further research on the molecular regulatory mechanism of embryonic muscle development in Chengkou mountain chicken and provide a reference for other poultry and livestock muscle development studies.
Intravascular Ultrasound-based Decision Tree Model for the Optimal Endovascular Treatment Strategy Selection of Femoropopliteal Artery Disease - Results from the ONION Study-
Authors: Yazu Yuko , Fujihara Masahiko , Takahara Mitsuyoshi , Kurata Naoya , Nakata Aya , Yoshimura Hitoshi , Ito Tomoaki , Fukunaga Masashi , Kozuki Amane , Tomoi Yusuke
Published: May 2022

Background: The role of catheter-based imaging in peripheral interventions for lower extremity artery disease has increased with percutaneous interventions. To clarify the relation between intravascular ultrasound (IVUS) information and procedure selection strategy for endovascular treatment therapy (EVT) of the femoropopliteal artery in the real-world clinical settings wherein new endovascular technologies (NETs), including drug-coated balloon (DCB), drug-eluting stent (DES), and covered stent-graft (CS). Our retrospective multicenter analysis examined symptomatic 970 patients treated by EVT for de novo femoropopliteal lesions with IVUS guidance. The decision tree analysis was performed retrospectively to determine the association of IVUS and angiography parameters with the strategy selection of endovascular procedures. We divided the study population according to the developed tree, and identified the most popular strategy selection in each subgroup. We finally examined whether the restenosis risk would be different among respective subgroups of the tree.Results: During the study periods, plain old balloon angioplasty, DCB, and bare nitinol stent were most frequently selected (25.3%, 23.9%, and 23.8%, respectively). The drug-eluting stent (DES), covered stent (CS), and spot stent strategies were used in 7.3%, 11.5%, and 8.1%. NETs had the lowest restenosis risk in the overall population. The decision tree had a depth of six branches and divided the patients into 11 subgroups by IVUS and angiography parameters. The restenosis rate was similarly low among these 11 subgroups when the most popular NET in each subgroup was selected (P = 0.94).Conclusions: The use of IVUS data along with angiography data would standardize the selection of endovascular procedures and can improve patency outcomes if NETs are used properly.
Lessons Learned for Drought Cities: Promising Steps towards Water Sensitive Urban Design in Arid and Semi-arid Cities
Authors: ElZein Zeina , Abdou Amal , Säumel Ina
Published: May 2022

Water security is one of the main challenges facing urban areas in arid or semi-arid zones. Egyptian cities need to deal with both insufficient quantity and quality of water for residents. Here we provide proposed actions and policies to allow transition towards water sensitive urban design in order to respond to water challenges in Egypt. Based on a systematic literature review, we have selected a set of criteria concerning the environmental, economic, social, governmental, and infrastructural dimensions of urban water management. We compiled and compared management approaches from Lima, Windhoek, and Adelaide. The three cities have climatic conditions and water issues similar to Egyptian cities and have made substantial advances towards sustainable water management. We then evaluated which elements can be adapted and used in Egypt. Proposed actions included participatory approaches that engage the community in water management, educational campaigns that lead to change of public perception, and assessment of water services through customers’ satisfaction.
The core bacteria of Fucus distichus include apparent seaweed generalists
Authors: Park Jungsoo , Davis Katherine , Lajoie Geneviève , Parfrey Laura Wegener
Published: May 2022

Background
Identifying the meaningful ecological associations between host and components of the microbiome is challenging. This is especially true for hosts where the taxonomic composition of the microbiome is highly diverse and variable in space and time such as marine macroalgae. Identifying core taxa is one way forward. This study leverages a large dataset of microbial communities associated with the widespread brown seaweed, Fucus distichus, at multiple spatial and temporal scales. We compare two different methodological approaches to identify core taxa at the amplicon sequence variant (ASV) level from this dataset: simple frequency analysis of F. distichus alone over the whole dataset, and an iterative indicator species analysis method identifies prevalent taxa that are consistently enriched on F. distichus in comparison to the local environment (IndVal). We then evaluate host-specificity of the identified F. distichus core ASVs using comparative data from 35 other seaweed species sampled at one of the sites.
Results
No bacterial taxa were at 100% prevalence in F. distichus samples, and IndVal identified a diverse array of F. distichus indicator taxa across sites and over time. Across the entire dataset, a set of eleven core ASVs were identified by both frequency analysis and IndVal. Frequency analysis captured a broader suit of core taxa, while IndVal was better at identifying host-specific microbes. Many Fucus-core ASVs, particularly within Granulosicoccus and Litorimonas are found on diverse seaweed species, while we find evidence of specificity to brown algae or Fucus for a few ASVs within Blastopirellula and Rubritalea.
Conclusions
We identified a suite of core taxa that are consistently associated with F. distichus and enriched in comparison to the environment, despite variation in the prevalent and predominant taxa on F. distichus over space and time. Moreover, we show that most of these core ASVs of F. distichus are found on diverse seaweed hosts, indicating that most occupy a seaweed generalist niche rather than forming highly specialized associations with F. distichus. Further studies should test whether seaweed generalists or specialists are more likely to engage in biologically important exchanges with host.
Is there Variation in Utilization of Preoperative Tests Among Patients Undergoing Total Hip and Knee Replacement in the US, and Does It Affect Outcomes? A Population-based Analysis
Authors: Hasan Mohamed , Kang Raymond , Lee Jungwha (Julia) , Beal Matthew , Ahmed Abdalrahman , Tian Yao , Ghomrawi Hassan M.K.
Published: May 2022

Study Objective:To describe recent practice patterns of preoperative tests and to examine their association with 90-day all-cause readmissions and length of stay.Design: Retrospective cohort study using the New York Statewide Planning and Research Cooperative System (SPARCS).Setting: SPARCS from March 1, 2016, to July 1, 2017.Participants: Adults undergoing Total Hip Replacement (THR) or Total Knee Replacement (TKR) had a preoperative screening outpatient visit within two months before their surgery.Interventions: Electrocardiogram (EKG), chest X-ray, and seven preoperative laboratory tests (RBCs antibody screen, Prothrombin time (PT) and Thromboplastin time, Metabolic Panel, Complete Blood Count (CBC), Methicillin Resistance Staphylococcus Aureus (MRSA) Nasal DNA probe, Urine analysis, Urine culture) were identified. Primary and Secondary Outcome Measures: Regression analyses were utilized to determine the association between each preoperative test and two postoperative outcomes (90-day all-cause readmission and length of stay). Regression models adjusted for hospital-level random effects, patient demographics, insurance, hospital TKR, THR surgical volume, and comorbidities. Sensitivity analysis was conducted using the subset of patients with no comorbidities.Results:55,099 patients (60% Female, mean age 66.1+/-9.8 SD) were included. The most common tests were metabolic panel (74.5%), CBC (66.8%), and RBCs antibody screen (58.8%). The least common tests were MRSA Nasal DNA probe (13.0%), EKG (11.7%), urine culture (10.7%), and chest X-ray (7.9%). MRSA testing, urine culture, and EKG were associated with a lower likelihood of 90-day all-cause readmissions. No tests were associated with the length of hospital stay. Results were similar in the subset with no comorbidities.Conclusions:Wide variation exists in preoperative tests before THR and TKR. We identified three preoperative tests that may play a role in reducing readmissions. Further investigation is needed to evaluate these findings using more granular clinical data.
3D printed scaffold for repairing bone defects in apical periodontitis
Authors: Li Cong , Xu Xiaoyin , Gao Jing , Zhang Xiaoyan , Chen Yao , Li Ruixin , Shen Jing
Published: May 2022

Objectives
To investigate the feasibility of the 3D printed scaffold for periapical bone defects.
Methods
In this study, KSL-W @PLGA microspheres were firstly prepared, the drug release behavior and bacteriostatic ability against E.faecalis and P.gingivalis were studied. After that, we prepared the KSL-W @PLGA microspheres/collagen/silk fibroin/nano-hydroxyapatite scaffold, meanwhile, the pore size, porosity, water absorption expansion rate and mechanical properties were measured. Also, MC3T3-E1 cells were seeded into sterile scaffold materials and investigated by CCK-8, SEM, and HE staining. In the animal experiment section, we constructed bone defect models of the mandible in vivo and evaluated its effect of bone formation. The Japanese white rabbits were killed at 1 and 2 months after surgery, the CBCT scanning, micro-CT scanning and HE staining analysis were performed on the samples of the operation area, respectively. Data were analyzed using ANOVA and LSD test. (α = 0.05).
Results
We observed that the KSL-W@PLGA sustainable-release microspheres prepared in the experiment were uniform in morphology and could slowly release the antimicrobial peptide (KSL-W), which had a long-term antibacterial effect. The prepared scaffold materials had good biocompatibility, while MC3T3-E1 cells were present on the surface of the scaffold with good morphology. The rabbit experiments showed that there was more new bone formation in the scaffold group according to histological and radiographic examinations.
Conclusions
The biological and mechanical properties of the 3D printed scaffold meet the requirements of bone tissue engineering. It is expected to be applied to the repair of bone defects in apical periodontitis.
Clinical Significance
The 3D printed scaffold not only has antibacterial effect, but also can promote bone tissue formation, which provides an alternative treatment option in apical periodontitis.
On mortality modelling using a density-hazard distribution
Authors: Ngataman Nuraini , Bakar Shaiful Anuar Abu
Published: May 2022

This paper analyzes a new parametric distribution from a family of density-hazard distribution for mortality modelling. The performance of the distribution is assessed using real United States mortality data and compared to an existing study demonstrating a three-parameter logistic distribution employing similar data. Parameter estimation is performed using the nonlinear least squares method. The result shows that the density-hazard distribution consistently gives a better fit for the United States male, female and total population data than the three-parameter logistic distribution for a 60-year period of study with the conclusion derived from the mean square error. In addition, the estimated life expectancy with an underlying density-hazard distribution gives proximity to its empirical counterparts for almost all age groups.
Animal Pose Estimation Algorithm Based on the Lightweight Stacked Hourglass Network
Authors: Wenwen Zhang , Yang Xu , Rui Bai , Li Li
Published: May 2022

Pose estimation has been a hot topic in the field of machine vision in recent years. In the pose estimation task, a lightweight stacked hourglass network (SHN) algorithm is proposed. Moreover, aiming at the problem of large parameters in depthwise convolutional neural networks, a lightweight residual module is proposed, that is, based on the lightweight efficient channel attention improved conditional channel-weighted method (ICCW-Bottle), which replaces bottleneck module, thereby reducing the weight of the network and obtaining the feature information of different scales. Given the problem that a large amount of feature information is easily lost after the network pooling operation, a lightweight dual-branch fusion module is proposed that fully integrates high-level semantic information and low-level detailed features under the condition of a small number of parameters. Finally, the training model of synthetic animal dataset and real animal dataset was jointly applied. Compared with the consistency-constrained semi-supervised learning (CC-SSL) method, the proposed method increased in accuracy of pose estimation by 5.5%. It also reduced the number of network parameters and the calculation amount. The results of the ablation experiment verify the advancement and effectiveness of the overall network.
Assessing Walking Ability Using a Robotic Gait Trainer: Opportunities and Limitations of Assist-as-Needed Control in Spinal Cord Injury
Authors: Maggioni Serena , Lünenburger Lars , Riener Robert , Curt Armin , Bolliger Marc , Melendez-Calderon Alejandro
Published: May 2022

Background: Walking impairments are a common consequence of neurological disorders and are assessed with clinical scores that suffer from several limitations. Robot-assisted locomotor training is becoming an established clinical practice. Besides training, these devices could be used for assessing walking ability in a controlled environment. Here, we propose an adaptive Assist-as-Needed (AAN) control for a treadmill-based robotic exoskeleton, the Lokomat, that reduces the support of the device (body weight support and impedance of the robotic joints) based on the ability of the patient to follow a gait pattern displayed on screen. We hypothesize that the converged values of robotic support provide valid and reliable information about individuals’ walking ability.Methods: Fifteen participants with Spinal Cord Injury and twelve controls used the AAN software in the Lokomat twice within a week and were assessed using clinical scores (10MWT, TUG). We used a regression method to identify the robotic measure that could provide the most relevant information about walking ability and determined the test-retest reliability. We also checked whether this result could be extrapolated to non-ambulatory and to unimpaired subjects. Results: The AAN controller could be used in patients with different injury severity levels. A linear model based on one variable (robotic knee stiffness at terminal swing) could explain 74% of the variance in the 10MWT and 61% in the TUG in ambulatory patients and showed good relative reliability but poor absolute reliability. Adding the variable ‘maximum hip flexor torque’ to the model increased the explained variance above 85%. This did not extend to non-ambulatory nor to able-bodied individuals, where variables related to stance phase and to push-off phase seem more relevant.Conclusions: The novel AAN software for the Lokomat can be used to quantify the support required by a patient while performing robotic gait training. The adaptive software might enable more challenging training conditions tuned to the ability of the individuals. While the current implementation is not ready for assessment in clinical practice, we could demonstrate that this approach is safe, and it could be integrated as assist-as-needed training, rather than as assessment. Trial registration: ClinicalTrials.gov Identifier: NCT02425332
Deregulation in binding and expression of RNA binding proteins as a mechanism of CD19-negative B-ALL
Authors: Ziegler Nicole , Cortés-López Mariela , Alt Francesca , Sprang Maximilian , Lehmann Nadine , Malki Khalifa El , Wingerter Arthur , Russo Alexandra , Beck Olaf , Attig Sebastian , Roth Lea , König Julian , Paret Claudia , Faber Jörg
Published: May 2022

Despite massive improvements in the treatment of B-ALL through CART-19 immunotherapy, a large number of patients suffer a relapse due to loss of the targeted epitope. Mutations in the CD19 locus and aberrant splicing events are known to account for the absence of surface antigen. However, the molecular determinants are not fully enlightened so far. We applied deep sequencing to analyze the CD19 locus in a cohort of B-ALL patients and identified a blast-specific 2-nucleotide deletion in intron 2 that exists in 35% of samples at initial diagnosis. Remarkably, no disease-specific mutation in the coding region was detected. We show that this deletion affects the binding site of RNA binding proteins (RBPs) including PTBP1. Moreover, we show that downregulation of PTBP1 in 697 cells reduces CD19 total protein by increasing intron 2 retention. Isoform analysis in patient samples revealed that blasts, at diagnosis, express increased amounts of CD19 intron 2 retention compared to normal B cells. By RNAseq and qRT-PCR, we could identify several RBPs being deregulated in leukemic blasts.Our data suggest that loss of RBP functionality by mutations altering their binding motifs or by deregulated expression might harbor the potential for the disease-associated accumulation of therapy-resistant CD19 isoforms.
Regulation of Community Advisory Boards During Conduct of Clinical Trials in Uganda; a qualitative study involving Stakeholders
Authors: Mijumbi Andrew Ojok , Mugenyi Levicatus , Nanfuka Mastula , Agaba Collins , Ochieng Joseph
Published: May 2022

Background: Community advisory structures such as Community Advisory Boards (CABs) play an important role of helping researchers to better understand the community at each phase of the clinical trial. CABs can be a source of accurate information on the community, its perception of proposed research and may identify factors that make community members vulnerable to the problem under investigation. Although CABs help to build mutually beneficial relationships between the researcher(s) and the communities in which the clinical trial is being implemented, meaningful engagement would require ethical guidance and regulatory oversight. The study assessed the stakeholders’ perspectives regarding the regulatory oversight of CABs in Uganda Methods: This was a cross-sectional study employing qualitative methods of data collection and analysis. Key informant interviews (KIIs) with the trial investigators, CAB chairpersons, community liaison officers, regulators and REC chairpersons were conducted. A KII guide was designed and utilized during key informant interviews. The guide included questions on role of investigators and CAB members in clinical trials; challenges of community engagement; facilitation of CABs; regulatory oversight of CABs; work relationships between investigators and CABs; and opinions on how community trials should be conducted among others. All interviews were conducted in English. Qualitative data were transcribed verbatim. A code book was generated based on the transcripts and study objectives. Thematic analysis was used to analyze qualitative data in Atlas ti based on emerging themes and sub-themes and in line with the study objectives. Results: Of the 34 respondents, 29.4% were investigators, 29.4% CAB chairpersons, 29.4% research regulators/REC Chairs and 11.8% community liaison officers. Fifty-nine percent were male and had varying occupations and demographic characteristics. Content analysis identified themes including the current practices for CAB establishment and monitoring; need for regulatory oversight; appropriate training and skills; and challenges faced by CABs. Conclusion: There is need for regulatory oversight of CABs based on contextualized ethical guidelines as well as capacity strengthening in terms of training and skills development.
Daunorubicin induces Cysteine‐rich protein 61 to decreases the Chemosensitivity through the ATM/NF-κB pathway in B-acute lymphoblastic leukemia
Authors: Shi# Pengchong , Lin# Zhen , Song Yanfang , Li Zhaozhong , Zeng Menglu , Luo Li , Cao Yingping , Zhu Xianjin
Published: May 2022

Background: Acute lymphoblastic leukemia（ALL）is the second most common hematologic malignancy worldwide with B-acute lymphoblastic leukemia（B-ALL）accounting for 70%-80%. Cysteine‐rich protein 61 (Cyr61), a potential tumor-promoting factor, is increased in both serum and bone marrow of B-ALL patients in our previous study. We aimed to elucidate the role of Cyr61 in B-ALL as well as to explore the source of Cyr61 in the bone marrow of B-ALL patients.Methods: The human B-ALL cell line Nalm-6 was used. Cyr61 expression levels were measured by using quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and western blot analysis. The biological functions of Cyr61 in regulating B-ALL cell chemosensitivity to DNR and VCR was detected by cell viability assay and flow cytometry analysis. The production mechanisms of Cyr61 in the bone marrow were measured by qRT-PCR and western blot analysis.Results: Knockdown of Cyr61 increased the chemosensitivity of Nalm-6 cells to DNR and VCR, and overexpression of Cyr61 decreased the chemosensitivity of Nalm-6 cells to DNR and VCR. Mechanistically, we found that Cyr61 attenuated chemotherapeutic drug-induced apoptosis by the upregulation of Bcl-2. Importantly, Cyr61 can be up-regulated by the chemotherapeutic drug DNR through the ATM-dependent NF-κ B pathway, however, VCR has no effect on the expression of Cyr61 in B-All cells.Conclusions: In conclusion, our study revealed that DNR can induce the production of Cyr61 in B-ALL cells; further, increasing Cyr61 decreased the chemosensitivity of B-ALL cells to chemotherapeutic drugs. Thus, targeting Cyr61 may be a promising therapeutic strategy to increase the chemotherapy sensitivity in patients with B-ALL.
Calmodulin Functionalized Porous Silicon Based Electrical Calcium Detector and its Comparison with Optical Detector
Authors: Sen Kaustav , Sarkar Tanusree , Basu Deeparati , Hossain Syed Minhaz , Das Jayoti
Published: May 2022

In this work a bi-parametric, highly selective, electrical calcium detecting platform is fabricated. The fabricated detector consists of porous silicon substrate which is surface functionalized by calmodulin. The use of porous silicon provides many fold increment in surface area, facilitating effective absorption, where as calmodulin functionalization upon the porous surface provides excellent calcium attachment sites. The electrical parameters of this detecting platform are then tested with calcium and several other ionic solutions, at concentration relevant physiologically. The fabricated detector showed tremendous selectivity towards calcium ion. Even in mixture ionic solution the detector exhibited its high discrimination towards calcium ion. Thus the fabricated detecting platform can work as an effective calcium detector. Its bi-parametric approach provides enhanced calcium detection efficiency. Hence the detector imparts a highly selective, robust, label free and cost-effective alternative for calcium detectors, effective even in biologically relevant concentrations. Later a comparative study is performed between the optical and electrical response of the detector platform to provide a better understanding of the consistency of the detector developed that in future will facilitate multi-parametric approach to enhance the response, selectivity and thus the efficiency of the detector platform developed in this work.
Ivermectin compared with placebo in the clinical evolution of Mexican patients with asymptomatic and mild COVID-19: a randomized clinical trial
Authors: Rocha Carmen de la , Cid-Lopez Marco A , Venegas-Lopez Blanca I , Gómez-Mendez Sandra C , Sánchez-Ortiz Adriana , Pérez-Ríos Alma M , Llamas-Velazquez Ricardo A , Meza-Acuña Aidé I , Vargas-Íñiguez Bárbara , Rosales-Galván Daniela , Tavares-Valdez Alejandra , Luna-Gudiño Nizdali , Hernandez-Puente Cinthia V , Milenkovic Jovana , Iglesias-Palomares Cecilia , Villar Miriam Méndez-del , Gutierrez-Dieck Gerardo A , Valderrábano-Roldán Carlos G , Mercado-Cerda Jennefer , Robles-Bojorquez Jocelyn G , Sesma Arieh Roldan Mercado
Published: May 2022

Background
Despite the development and application of vaccines against SARS-CoV-2 around the world, the scientific community still tried to find some therapies to avoid or ameliorate the fatal evolution of the COVID-19. Since the publication of the potential use of Ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo.
Methods
A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to Ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days.
Results
None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5 and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group.
Conclusions
At standard doses, ivermectin is not effective in the progression to severe state and reducing symptoms in adults with asymptomatic and mild COVID-19.
Trial registration
The study was registered with ClinicalTrial.gov (NCT04407507)
Premature Infants Receiving Delayed Cord Clamping with and without Cord Milking: A Randomized Control Trial
Authors: Prachukthum Sariya , Tanprasertkul Chamnan , Somprasit Charintip
Published: May 2022

Background: Premature babies often have long hospital stays and frequent blood tests; they often develop anemia requiring multiple blood transfusions. Placental transfusion via delayed cord clamping (DCC) or umbilical cord milking (UCM) helps increase blood volume. We hypothesized umbilical cord milking (UCM), together with DCC, would be a superior in reducing blood transfusions.Objectives: To compare the effects of DCC and DCC combined with UCM on hematologic outcomes among preterm infants. Methods: 120 singleton preterm infants born at 280/7- 336/7 weeks of gestation at Thammasat University Hospital were enrolled in a randomized controlled, open label, trial. They were placed into three groups (1:1:1) by a block-of-three randomization: DCC for 45 seconds, DCC with UCM performed before clamping (DCM-B), and DCC with UCM performed after clamping (DCM-A). The primary outcomes were hematocrit levels and number of infants receiving blood transfusions during the first 28 days of life. Intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC) were secondary outcomes. Analysis were performed with an intent-to-treat approach.Results: 120 preterm infants were randomized. There was no statistically significant difference in neonatal outcomes; hematocrit on admission 54.0 ± 5.5, 53.3 ± 6.0, and 54.3 ± 5.8, receiving blood transfusions 25%, 20% and 12.5%, incidence of NEC 7.5, 0 and 10% in the DCC, DCM-B and DCM-A groups, respectively. There were no preterm infants with severe IVH, polycythemia, maternal or neonatal death.Conclusion: Although it was not significantly different, preterm infants in DCM-B and DCM-A groups requiring blood transfusion were less than those in DCC group. All three placental transfusion techniques provided the same benefit in preterm infants in reducing the incidence of severe IVH and NEC without increasing complication and comorbidity. Trial Registration: TCTR20190131002Registered 31 January 2019 - Retrospectively registered http://www.thaiclinicaltrials.org/show/TCTR20190131002
Pharmacophore optimization of substituted N-phenyl-2,2-dichloroacetamide using molecular modelling studies, design, ADMET prediction, synthesis and evaluation of potential anti-cancer agents.
Authors: Bhandari Shashikant V. , Nagras Om G. , Kuthe Pranali V. , Sarkate Aniket P. , Pathak Vrushali P.
Published: May 2022

A current study shows that N-phenyl-2, 2-dichloroacetamide analogues can induce cancer cell apoptosis and inhibit tumor growth by inhibiting the enzyme Pyruvate Dehydrogenase Kinase (PDK), but they have not been proved as clinically promising anticancer agents due to their low biological activity as well as toxicity profile. Hence Two-dimensional (2D), Three-dimensional (3D) and Group based (G) Quantitative Structure Activity Relationship (QSAR) studies were performed to correlate the chemical composition of N-phenyl-2,2-dichloroacetamide analogues with their anticancer activity in order to optimize the pharmacophore requirements for potent PDK inhibitors. New Molecular Entities (NMEs) were designed using the results of all QSAR studies. Binding affinities of designed NMEs were studied on PDK II & PDK I enzymes (PDB code: 2BU8 & 2Q8H respectively) using molecular docking studies. The ADMET properties of designed NMEs were also predicted to ensure their drug like pharmacokinetic profile. Results of molecular modeling studies were cross verified by synthesis and testing the designed compounds by cytotoxicity assay using A549 cell line. Compound D4 exhibited very significant anti proliferative effect. The potency in order was observed as below compounds [Most potent] D4(IC50 = 0.167µm/ml) > D5(IC50 = 0.191µm/ml) > D8(IC50 = 0.218µm/ml) > D9(IC50 = 0.238µm/ml) > D11(IC50 = 0.290µm/ml) > D12(IC50 = 0.409µm/ml) > [Least potent] D14(IC50 = 0.635µm/ml). All the designed compounds were found to be more potent as compared to most potent compounds of the selected series. Thus, compound D4 and D5 with potent inhibitory activity in tumor growth inhibition were found be a potential anticancer agent.
Reverse osmosis water desalination plants and environmental impacts
Authors: Rezaei Leila , Alipour Vali , Dehghani Mohsen , Hassani Amir Hesam
Published: May 2022

This case-control study was conducted to investigate the possibility of pollution caused by reverse osmosis desalination wastewater discharge into the coastal environment from spring 2019 to fall 2020. Five sites (wastewater receiving) and two sites (checkpoint) were selected in Bandar Abbas coast. Seawater, plant waste, and coastal sediments were sampled 63 times at checkpoints and cases. The physical, chemical, heavy metals and plankton were measured. The environmental pollution indices including pollution coefficient, pollution load, enrichment, toxicity potential were determined. The EC and heavy metal concentration (Pb, Cu, Ni, Cd, zinc and Fe) values in the checkpoint were significantly higher than the control stations. The plankton counts in the control stations was more than checkpoint. The pollution indices show low to moderate pollution levels of the banks of the desalination plant. Desalination plants have the potential to adversely affect coastal ecosystems; monitoring and management programs need to be implemented more extensively.
Double-kill mechanism of artemisinin against Plasmodium
Authors: Sun Jun , Guo Fujiang , Liu Chuang , Chen Bo , Xu Wenyue , Li Jia , Du Xiling , Liu Yixian , Wang Yu
Published: May 2022

Artemisinin and its derivatives (ARTs) can kill malaria parasites, but its mechanism remains unclear. Haem or iron (HI) was proposed to activate ARTs to produce free radicals that kill malaria parasites. However, our results revealed that adding iron supply did not enhance the antimalarial effect of ARTs but attenuated this effect, strongly suggesting that its free radical effect was not its only antimalarial mechanism. Single-cell RNA sequencing analysis of Plasmodium yoelii 17XNL-infected erythrocytes revealed that the stages most sensitive to ARTs were closely associated with the expression of haem- and iron- related, DNA synthesis-related, antioxidation-related, and pentose-phosphate-pathway-related genes, simultaneously accompanied with the release and utilization of HI. In addition, ARTs were found to combine with haem to form adducts and disturb the normal aggregation of hemozoin in parasites. In particular, adding iron supply antagonized the antimalarial effect of ARTs in vivo and in vitro, strongly suggesting that ARTs trap HI and disturb the requirement of parasites dependent of HI, thereby resulting in the antimalarial effect, which is likely similar to the antimalarial mechanism of iron chelators. Thus, the iron chelator effect with free radical effect renders ARTs the double-kill antimalarial mechanism.
Taper up-off treatment of opium may reverse some dysregulations of gene expression patterns caused by four type of leukemia, AML, ALL, CML and CLL; a pilot animal model study
Authors: Dezhakam Hossein , Dezhakam Ani , Haghighatfard Arvin
Published: May 2022

Leukemia is a group of lethal diseases characterized by hematological neoplasm with complex and abnormalities in proliferation of bone marrow stem cells, that cause sever loss of functional capacity of hematopoietic tissue. Four most common types of leukemia are included acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML). It has been reported that opium besides of pain killer effects, may have positive effects on cardiovascular disease treatments. Opium may consider as a potential treatment method in cancer. The present study aimed to assess the gene expression pattern alterations in the rat models of four types of Leukemia (ALL, AML, CLL, and CML) under taper up-off treatment method with of opium. Present study was included twelve group, referred to four type of Leukemia (ALL, AML, CLL, and CML) that each type studied in three group. Group one contented normal rats, group two rat model of each type of leukemia with no treatment and group three the rat model of that type of leukemia with 26 days period of opium taper up-off treatment. After the scarification of rats, the bone marrow tissue were extracted. Then, RNA extraction and cDNA synthesis had been conducted on bone marrow tissues. Whole genome expression profiling was conducted by using the Affymetrix GeneChip Array Platform. Microarray results were confirmed by Real time PCR. Microarray analysis detected that hundreds of genes which were involved in Ontogenesis and apoptosis, humoral immune system, tool like receptors, natural killer cells regulators and metabolic pathways and were deregulated in leukemic models, were partially reregulated in treatment groups. Results showed that opium may have positive effects on reregulation of affected gene expression patterns in all types of leukemia. It may suggest that opium taper up-off treatment could be consider as re-regulator of immune system and a novel potential treatment for leukemia with low side effects and high viability.
Langar: An Approach to Evaluate Reo Programming Language
Authors: Besharati Mohammad Reza , Izadi Mohammad
Published: May 2022

Reo is a formal coordination language. In order to assess and evaluate its capabilities, we need a multi-perspective Language Evaluation Framework. Langar (Language Analysis for Reo) is a framework aimed to provide such an evaluation method. In this paper, we introduce Langar. Based on a review on various language evaluation methods, a tool-kit for useful evaluation techniques are provided. After Reo Evaluation, this method and tool-kit also could be used for another programming, computational and even natural languages. Furthermore, two suggestions for some future efforts and directions are provided for software engineering and software methodology communities.
Liraglutide ameliorates diabetic cardiomyopathy via activating Cav3/eNOS/NO signaling and enhancing interaction of Cav3 with RyR2
Authors: Li Xu , Ni Zebin , Wang Junwu , Ye Xiuying , Shen Yujing , Liu Ruohai , Pan Wei , Cao Hong , Wu Wenjun
Published: May 2022

Purpose
Liraglutide (LIRA), a Glucagon-like peptide-1 receptor agonist (GLP-1RA), showed potent cardioprotective effects of diabetic cardiomyopathy (DCM) with the mechanism remained incompletely understood.
Methods
T2DM rats were used as study subjects and randomly divided into four groups: 1) CON group, 2) CON + L group, 3) DM group and 4) DM + L group. All rats received either saline or LIRA 0.2 mg/kg (by i.p injection) per day for 4 weeks. After the model was successfully established, cardiac function was determined by invasive hemodynamic evaluation methods. Immunohistochemistry and western blot were performed to understand the molecular mechanism between cardiac function and LIRA. Cultured H9C2 cells with small interfering RNA (siRNA) of Cav3 under high glucose (HG), western blot was performed to understand the molecular mechanism between Cav3 and RyR2 with LIRA.
Results
Based on our results, LIRA treatment showed a trend to enhance LVSP (110.76 ± 5.61 mmHg) and ± dp/dtmax (5860.41 ± 200.32 mmHg and 3996.8 ± 179.3 mmHg), decreased LVEDP (7.23 ± 0.58 mmHg). The expression of Cav3, eNOS and RyR2 was significantly decreased in the myocardium in DM group, which increased in DM + L group after LIRA administrated. LIRA improved cardiac systolic and diastolic function, attenuate diabetic cardiomyopathy injury by improving Cav3/eNOS/NO signaling and increasing interaction of Cav3 and ryanodine receptor 2 (RyR2) in diabetic cardiac tissues.
Conclusion
In summary, we found that Liraglutide ameliorates cardiac dysfunction in rats with type 2 diabetes mellitus via improving Cav3/eNOS/NO signaling and increasing interaction of Cav3 and RyR2.
Evaluating the performance of multi-criteria decision making techniques in flood susceptibility mapping
Authors: Mahato Ranjit , Bushi Dhoni , Nimasow Gibji , Barman Bikul , Joshi Ramesh , Yadava Ram Sakal
Published: May 2022

Performances of multi-criteria decision making techniques in prediction of flood susceptibility are varied. We evaluated performances of ARAS, CODAS, COPRAS, EDAS, MOORA, TOPSIS, VIKOR, and WASPAS in predicting flood susceptibility of Barpeta district of Assam, India. Elevation, slope, proximity to river, geomorphology, drainage density, rainfall, land use/ land cover, lithology, soil, stream power index, topographic wetness index and plan curvature were used as flood conditioning factors. The results show higher flood susceptibility over areas characterized by gentle slopes, low elevation and high proximity to drainage. Performances of the models were evaluated using area under receiver operating characteristic (ROC) curve (AUC). TOPSIS model showed better success (AUC = 0.965) and prediction rate (AUC = 0.962) than other models. Among the best performing models, highest percentage of area under high flood susceptibility was predicted by TOPSIS. Therefore, TOPSIS can be effectively used for flood risk management in areas having similar geographical conditions.
Enduring and Instant H2O2 Generation via Controlled Coupling Transfer
Authors: Zhao Yong-Yan , He Jing-Hui , Duan Guangxin , Lu Jian-Mei
Published: May 2022

Extremely slow kinetics and limited accumulation of H2O2 during the oxygen reduction reaction, which derives from the negative effects of diffusion-limited and further catalysis, are the grant challenges seriously hindering the development of green H2O2 synthesis. Herein, we first controlled the coupling energy of the proton and electron by periodic-potential-driven catalysis, achieving 56-fold greater H2O2 accumulation than that generated by constant-potential catalysis. To modulate proton and electron coupling transfer, we employed optimized dual-electrolytes to achieve a rate of 45900 mmol gcat−1 h− 1, and provided strong evidence of molecular-level understanding via comprehensive microenvironment simulation. These results were obtained with a pyrolytic metal/reduced cage crystal (RCC1) catalyst with stable performance reaching 3.6 million pulses, which generated products that can be directly utilized for the complete removal of bacteria in 2 seconds from seawater. Our systemic methodology and in situ application are anticipated to aid in the design of innovative catalysts, provide a deep understanding of pulse and electrolyte effects, and aid in the design of a new effective cell system to achieve industry-level H2O2 production.