Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling of Antitumor Drug Pharmacodynamics Using Genetic algorithm

Available mathematical models of tumor growth and the effect of anticancer treatments in animals are still of limited practical use within the drug industry because of complex and contradictory aspects. A simple and effective model would facilitate the preclinical development of oncology drugs owing to prediction capabilities. Another challenge of this field is to estimate the model parameters according to laboratory experimental data. Simplicity of mathematical models often causes a major impediment in fitting the models to experimental data. In this paper, a minimal Pharmacokinetic-Pharmacodynamic (PKPD) model is studied to analyze the effects of antitumor drugs using empirical data obtained from the experimentations on 5 groups of laboratory mice: one group untreated and 4 groups treated with four different antitumor drugs which are intravenously administered. Tumor growth and process of cell death are here modeled by three differential equations obtained from a compartmental model. The related compartmental model is then applied to experimental data supposing an exponential decaying model for drug concentration. Using Genetic algorithms, the parameters of model have been optimally estimated. According to simulations, the proposed model copes with the interpretation of contradictory effects of CpG drug. Besides, the parameters of immunological system are uniquely obtained in the presence of different anticancer drugs. Proposed model parameters may be used in the prediction of an eventual treatment of mixing profile.
PathoPlant : ADatabas eo nPlant-Pathogen Interactions

Pathogen recognition and signal transduction during plant pathogenesis is essential for the activation of plant defense mechanisms. To facilitate easy access to published data and to permit comparative studies of different pathogen response pathways, a database is indispensable to give a broad overview of the components and reactions so far known. PathoPlant has been developed as a relational database to display relevant components and reactions involved in signal transduction related to plant-pathogen interactions. On the organism level, the tables 'plant', 'pathogen' and 'interaction' are used to describe incompatible interactions between plants and pathogens or diseases. On the molecular level, plant pathogenesis related information is organized in PathoPlant's main tables 'molecule', 'reaction' and 'location'. Signal transduction pathways are modeled as consecutive sequences of known molecules and corresponding reactions. PathoPlant entries are linked to associated internal records as well as to entries in external databases such as SWISS-PROT, GenBank, PubMed, and TRANSFAC . PathoPlant is available as a web-based service at http://www.pathoplant. de.
Refining surgical models of osteoarthritis in mice and rats alters pain phenotype but not joint pathology

The relationship between osteoarthritis (OA) structural change and pain is complex. Surgical models of OA in rodents are often rapid in onset, limiting mechanistic utility and translational validity. We aimed to investigate the effect of refining surgical small rodent models of OA on both joint pathology and pain behaviour. Adult male C57BL/6 mice (n = 76, 10–11 weeks of age at time of surgery) underwent either traditional (transection of the medial meniscotibial ligament [MMTL]) or modified (MMTL left intact, transection of the coronary ligaments) DMM surgery, or sham surgery. Adult male Sprague Dawley rats (n = 76, weight 175-199g) underwent either modified meniscal transection (MMNX) surgery (transection of the medial meniscus whilst the medial collateral ligament is left intact) or sham surgery. Pain behaviours (weight bearing asymmetry [in mice and rats] and paw withdrawal thresholds [in rats]) were measured pre-surgery and weekly up to 16 weeks post-surgery. Post-mortem knee joints were scored for cartilage damage, synovitis, and osteophyte size. There was a significant increase in weight bearing asymmetry from 13 weeks following traditional, but not modified, DMM surgery when compared to sham operated mice. Both traditional and modified DMM surgery led to similar joint pathology. There was significant pain behaviour from 6 weeks following MMNX model compared to sham operated control rats. Synovitis was significant 4 weeks after MMNX surgery, whereas significant chondropathy was first evident 8 weeks post-surgery, compared to sham controls. Pain behaviour is not always present despite significant changes in medial tibial plateau cartilage damage and synovitis, reflecting the heterogeneity seen in human OA. The development of a slowly progressing surgical model of OA pain in the rat suggests that synovitis precedes pain behaviour and that chondropathy is evident later, providing the foundations for future mechanistic studies into the disease.
Molecular docking between human TMPRSS2 and SARS-CoV-2 spike protein: conformation and intermolecular interactions

Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816. The present study aims to investigate the conformational attributes of the molecular complex between TMPRSS2 and SARS-CoV-2 spike protein, in order to discern the finer details of the priming of viral spike protein. Briefly, full length structural model of TMPRSS2 was developed and docked against the resolved structure of SARS-CoV-2 spike protein with directional restraints of both cleavage sites. The docking simulations showed that TMPRSS2 interacts with the two different loops of SARS-CoV-2 spike protein, each containing different cleavage sites. Key functional residues of TMPRSS2 (His296, Ser441 and Ser460) were found to interact with immediate flanking residues of cleavage sites of SARS-CoV-2 spike protein. Compared to the N-terminal cleavage site (Arg685/Ser686), TMPRSS2 region that interact with C-terminal cleavage site (Arg815/Ser816) of the SARS-CoV-2 spike protein was predicted as relatively more druggable. In summary, the present study provides structural characteristics of molecular complex between human TMPRSS2 and SARS-CoV-2 spike protein and points to the candidate drug targets that could further be exploited to direct structure base drug designing.
Involvement of the cerebellum in EMDR efficiency: a metabolic connectivity PET study in PTSD

ABSTRACT Background We recently reported an improvement of precuneus PET metabolism after EMDR therapy in military participants suffering from PTSD. Objective The aim of the present study was to investigate the metabolic changes of precuneus connectivity in these participants after such treatment. Method Fifteen participants with PTSD performed a brain 18F-FDG-PET sensitized by virtual reality exposure to war scenes, before and after EMDR treatment. Inter-regional correlation analysis was performed to study metabolic changes of precuneus connectivity through SPMT maps at whole-brain level (p < 0.005 for the voxel, p < 0.05 for the cluster). Results A decrease of connectivity was observed after EMDR between the precuneus and two significant bilateral clusters of the cerebellum (bilateral Crus I and VI cerebellar lobules, Tmax voxel of 5.8 and 5.3, and cluster size of 343 and 314 voxels, respectively). Moreover, higher cerebellar metabolism before treatment was associated with reduced clinical PTSD scores after EMDR (p = 0.03). Conclusions The posterior cerebellum and its metabolic connectivity with the precuneus are involved in the clinical efficiency of EMDR in PTSD.
Effect of the Dwarfing Gene From Dee-geo-woo-gen on Culm and Internode Lengths, and its Response to Fertilizer in Rice

The effect of the dwarfing gene from Dee-geo-woo-gen (in-dicated by d-47 in this study) on culm and internode lengths was investigated. Following isogenic dwarf lines were used : the two isogenic lines of d-47 of Shiokari and Taichung 65 (abbreviated to d-47 Iine and d-47(T65) Iine, respectively) ; and Calrose 76 (abbreviated to C76) which contains sd-1 at the same locus as d-47. Three Fl's be-tween the three dwarf lines and their respective parental cultivars, and two kinds of F2 populations were used. Two and three fertilizer levels were set for d-47 Iine and Shiokari, and d-47(T65) Iine and Taichung 65, respectively. The difference between d-47(T65) Iine and Taichung 65 in culm length was 28.0 cm under a condition of basal dress-ing, and the difference was 27% of the culm length of Taichung 65. Those between d-47 Iine and Shiokari were 27.0 cm and 38%. Those between C76 and Calrose were 20.0 cm and 19% . The difference in internode length be-tween each of dwarf lines and its parental cultivar became smaller from the first to 6th internodes.
Initial Rotational Instability of the Tapered Wedge-Shaped Type Cementless Stem

Background Because the tapered wedge-shaped type cementless stem has a small anteroposterior width and a low occupation rate in the medullary space, postoperative rotational instability and stem subsidence due to inadequate proximal fixation are concerns. The purpose of this study was to clarify the relationship between the rotational instability of the tapered wedge-shaped type cementless stem and femoral canal shape. Methods A total of 61 primary total hip arthroplasties with the tapered wedge-shaped type cementless stem Accolade® TMZF (11 males, 50 females; mean age 60 years) from January 2012 to June 2015 who underwent computed tomography before surgery and within 4 weeks and 1 year after surgery were evaluated. The preoperative femoral neck anteversion angle, preoperative femoral canal flair index, the degree of postoperative stem subsidence within 1 year after operation, and the degree of rotational change in the stem setting angle within 1 year after operation were investigated. Results The mean preoperative femoral neck anteversion angle was 32.2° ± 17.8° (0°–69°), and the mean preoperative canal flair index was 3.68 ± 0.58 (2.44–5.55). There were no stem subsidence cases within 1 year after operation. The mean degree of rotational change in the stem from immediately to 1 year after surgery was −0.4° ± 1.7° (−3°–3°). There was no significant correlation between the canal flair index and the rotational change in the stem. In addition, the mean difference between the preoperative femoral neck anteversion angle and the stem rotational angle immediately after surgery was only 1.3° ± 5.3° (−29°–15°). Conclusions In all cases, including stove-pipe cases, the degree of rotational change in the Accolade® TMZF stem from immediately to 1 year after surgery was within 3°. In other words, regardless of femoral canal shape, the tapered wedge-shaped type cementless stem has little initial rotational instability.
Survival Status and Predictors of Mortality among Newborns Admitted with Neonatal Sepsis at Public Hospitals in Ethiopia

Background One-fourth of neonatal death is due to neonatal sepsis and nearly 98% of these deaths are occurring at low- and middle-income countries. In Ethiopia, forty percent of under-five mortality occurs during the neonatal period, of which neonatal sepsis accounts for 30-35% of neonatal deaths next to prematurity and its complications. On the other side, among the survived neonates with neonatal sepsis, there exist as vulnerable to short and long-term neurological and developmental morbidity impacting the overall productivity of the child as adult. Methods A longitudinal prospective cohort study was conducted among selected 289 neonates with neonatal sepsis who were admitted in the neonatal intensive care unit at public hospitals in Ethiopia from 1st March 2018 to 31st December 2019. Data were entered into Epi data version 3.02 and exported to SPSS V 25 for analysis. The Kaplan-Meier survival curve together with log-rank test was used to estimate the survival time of the neonates. Variables which had p value < 0.05 in multivariable analysis using the cox proportional hazard model were declared as statistically significant predictors of mortality. Results The study was conducted with a total of 289 neonates admitted with neonatal sepsis. The cumulative proportion of surviving at the end of the fourth day was 99.5%, and it was 98.2% at the end of the fifth day. In addition, it was 96.6%, 93.5%, and 91.1% at the end of the sixth, seventh, and eighth day, respectively. The incidence of mortality was 8.65 per 100 neonates admitted with neonatal sepsis. Having a history of intrapartum fever (AHR: 14.5; 95% CI: 4.25, 49.5), history of chorioamnionitis (AHR: 5.7; 95% CI: 2.29, 13.98), induced labor (AHR: 7; 95% CI: 2.32, 21.08), and not initiating exclusive breastfeeding within one hour (AHR: 3.4; 95% CI: 1.34, 12.63) were the independent predictors of mortality. Conclusion The survival status of neonates among neonates admitted with neonatal sepsis was high at the early admission days and high cumulative proportion of death as the admission period increased. The risk of mortality was high among the neonates with early onset of neonatal sepsis as compared with late onset of neonatal sepsis and history of intrapartum fever, history of diagnosed chorioamnionitis, onset of labor, and EBF initiation within one hour were the independent predictors of mortality among neonates admitted with neonatal sepsis.
Essential Oils as Fumigants for Bed Bugs (Hemiptera: Cimicidae)

Abstract Certain plant-derived essential oils are classified as ‘minimum risk' pesticides that require no registration with the Environmental Protection Agency and, therefore, have become attractive in formulations of pest-control products. In Petri dish assays, fumigation of a pyrethroid-susceptible strain of bed bugs, Cimex lectularius L. (Hemiptera: Cimicidae), with various essential oils results in mortality that approaches or equals 100% after 5 d. However, when bed bugs were exposed to the same essential oils in sealed, commercial trash bags for 5 d, only rosemary oil killed greater than 99% of the bed bugs. These results are compared with a commercial product that contains cold-pressed neem oil that killed 100% of the exposed bed bugs in both the Petri dish and trash bag studies.
The Effect of Antenatal Care Service Utilization on Postnatal Care Service Utilization: A Systematic Review and Meta-analysis Study

Introduction Reduction of maternal and neonatal morbidity and mortality has continued to be a challenge in developing countries. The majority of maternal and neonatal mortality occurred during the early postpartum period. This is mostly due to low postnatal care service utilization. There is a discrepancy of evidence on the effect status of antenatal care on the improvement of postnatal care service utilization. Therefore, this review study is aimed at estimating the pooled effect of antenatal care on postnatal care service utilization. Methods We searched from PubMed and Cochrane library database, Google Scholar, and Google. Initially, we found 265 articles; after duplication was removed and screened by the relevance of the titles and abstracts, 36 studies were considered for assessment of eligibility. Finally, 14 articles passed the inclusion and exclusion criteria and are included in the meta-analysis. Study quality assessment was done using Janna Briggs Institute (JBI) critical appraisal tools. The main information was extracted from each study. Heterogeneity of studies was assessed using I2 = 70% and more considered having high heterogeneity. The publication bias was checked using funnel plot and big test. Meta-analysis using a random effect model was conducted. A forest plot was used to show the estimated size effect of odds ratio with a 95% confidence interval. Results A total of 14 articles were included with 15,765 participants for synthesis and meta-analysis. We found that a pooled estimate of women who had antenatal care was 1.53 times more likely to have postnatal care compared with those who had no antenatal care (AOR = 1.53, 95% CI 1.38-1.70, I2 = 0%). Conclusions This review results revealed a low utilization of postnatal care service. Antenatal care service utilization has a positive effect on postnatal care service utilization. Policymakers and programmers better considered more antenatal care service use as one strategy of enhancing the utilization of postnatal care service.
Transcriptome analysis based on RNA-seq of common innate immune responses of flounder cells to IHNV, VHSV, and HIRRV

Viral hemorrhagic septicemia virus (VHSV) and hirame rhabdovirus (HIRRV) belong to the genus Novirhabdovirus and are the causative agents of a serious disease in cultured flounder. However, infectious hematopoietic necrosis virus (IHNV), a prototype of the genus Novirhabdovirus, does not cause disease in flounder. To determine whether IHNV growth is restricted in flounder cells, we compared the growth of IHNV with that of VHSV and HIRRV in hirame natural embryo (HINAE) cells infected with novirhabdoviruses at 1 multiplicity of infection. Unexpectedly, we found that IHNV grew as well as VHSV and HIRRV. For successful growth in host cells, viruses modulate innate immune responses exerted by virus-infected cells. Our results suggest that IHNV, like VHSV and HIRRV, has evolved the ability to overcome the innate immune response of flounder cells. To determine the innate immune response genes of virus-infected HINAE cells which are commonly modulated by the three novirhabdoviruses, we infected HINAE cells with novirhabdoviruses at multiplicity of infection (MOI) 1 and performed an RNA sequencing-based transcriptome analysis at 24 h post-infection. We discovered ~12,500 unigenes altered by novirhabdovirus infection and found that many of these were involved in multiple cellular pathways. After novirhabdovirus infection, 170 genes involved in the innate immune response were differentially expressed compared to uninfected cells. Among them, 9 genes changed expression by more than 2-fold and were commonly modulated by all three novirhabdoviruses. Interferon regulatory factor 8 (IRF8), C-X-C motif chemokine receptor 1 (CXCR1), Toll/interleukin-1 receptor domain-containing adapter protein (TIRAP), cholesterol 25-hydroxylase (CH25H), C-X-C motif chemokine ligand 11, duplicate 5 (CXCL11.5), and Toll-like receptor 2 (TLR2) were up-regulated, whereas C-C motif chemokine receptor 6a (CCR6a), interleukin-12a (IL12a), and Toll-like receptor 1 (TLR1) were down-regulated. These genes have been reported to be involved in antiviral responses and, thus, their modulation may be critical for the growth of novirhabdovirus in flounder cells. This is the first report to identify innate immune response genes in flounder that are commonly modulated by IHNV, VHSV, and HIRRV. These data will provide new insights into how novirhabdoviruses survive the innate immune response of flounder cells.
Comparison of Performance on the Clock Drawing Test Using Three Different Scales in Dialysis Patients

Background The clock drawing test (CDT) is frequently used to detect changes in cognition. Multiple scales of varying length have been published to assess performance. The aim of this study is to compare the CDT performance measured by three scales among a sample of nondemented patients on renal dialysis and identify the variables that affect performance. Methodology. This is a cross-sectional study performed at the dialysis unit at King Saud University Medical City. Eighty-nine dialysis patients performed the CDT. The CDT was scored by the methods of Rouleau et al. (RCS 10-point), Babins et al. (BCS 18-point), and the MoCA (MCS 3-point). Regression models were used to determine influencing demographic and dialysis variables. Scores were then correlated, and a combined factor analysis of scale components was done. Results Females represented 44.6%, the mean (SD) age was 49.99 (15.49) years, and education duration was 10.29 (5.5) years. Dialysis vintage was 55.81 (62.91) months. The scores for the MCS, RCS, and BCS were 2.18 (1.08), 6.67 (3.07), and 11.8 (5.5), respectively, with significant correlation (P < 0.0001). In all scales, increasing age was associated with a lower score (each P < 0.0001). The scores increased with increasing education (each P < 0.0001). Diabetics had a lower score on both the BCS and MCS by 2.56 (SE 1.2) (P = 0.035) and 0.71 (P = 0.003) points, respectively. However, only age and years of education were significant in the multivariable analysis. In factor analysis, two shared factors appeared between the three scales: hand and number placement and the clock face. Conclusion Age and education influence the performance on the CDT, and factors diverged into executive and visuospatial components. The MCS is likely to yield useful information but should be interpreted as part of the MoCA.
Identifying risk factors for the prognosis of head and neck cutaneous squamous cell carcinoma: A systematic review and meta-analysis

In this study, we sought to identify the potential impacts of disease characteristics on the prognosis of cutaneous squamous cell carcinoma (cSCC). We searched the PubMed, EmBase, and Cochrane Library databases from their inception until February 2020 to identify studies that investigated the prognosis of cSCC. The pooled effect estimates were applied using odds ratios (OR) and 95% confidence intervals (CI) and were calculated using the random-effects model. Forty-three studies including a total of 21,530 patients and reporting 28,627 cases of cSCC were selected for the final meta-analysis. Poor differentiation (OR, 3.54; 95% CI, 2.30–5.46; P < 0.001), perineural invasion (OR, 3.27; 95% CI, 1.60–6.67; P = 0.001), Breslow greater than 2 mm (OR, 5.47; 95% CI, 2.63–11.37; P < 0.001), diameter greater than 20 mm (OR, 4.62; 95% CI, 2.95–7.23; P < 0.001), and location on temple (OR, 3.20; 95% CI, 1.12–9.15; P = 0.030) were associated with an increased risk of recurrence, whereas immunosuppression status and location on cheek, ear, or lip were not associated with the risk of recurrence. Poor differentiation (OR, 6.82; 95% CI, 4.66–9.99; P < 0.001); perineural invasion (OR, 7.15; 95% CI, 4.73–10.83; P < 0.001); Breslow greater than 2 mm (OR, 6.11; 95% CI, 4.05–9.21; P < 0.001); diameter greater than 20 mm (OR, 5.01; 95% CI, 2.56–9.80; P < 0.001); and location on ear (OR, 2.38; 95% CI, 1.39–4.09; P = 0.002), lip (OR, 2.15; 95% CI, 1.26–3.68; P = 0.005), and temple (OR, 2.77; 95% CI, 1.20–6.40; P = 0.017) were associated with an increased risk of metastasis, whereas immunosuppression status and location on cheek did not affect the risk of metastasis. Finally, poor differentiation (OR, 5.97; 95% CI, 1.82–19.62; P = 0.003), perineural invasion (OR, 6.64; 95% CI, 3.63–12.12; P < 0.001), and Breslow greater than 2 mm (OR, 3.42; 95% CI, 1.76–6.66; P < 0.001) were associated with an increased risk of disease-specific death, whereas diameter; immunosuppression status; and location on ear, lip, and temple did not affect the risk of disease-specific death. We found that differentiation, perineural invasion, depth, diameter, and location could affect the prognosis of cSCC. The potential role of other patient characteristics on the prognosis of cSCC should be identified in further large-scale prospective studies.