Nevin Manimala

Heliyon. 2023 Oct 17;9(10):e21085. doi: 10.1016/j.heliyon.2023.e21085. eCollection 2023 Oct.

ABSTRACT

As financial conditions become more complex and variable, capturing economic patterns becomes harder. The Financial Conditions Index (FCI) has gained traction as a tool to assess the performance of financial markets in nations or regions. This paragraph has created the China FCI using various financial indicators from 2002 to 2022. And with the use of statistical models like DMA-TVP-FAVAR, mixed-frequency Granger causality test, TVP-SV-VAR, and MS-VAR to analyze the relationship between China’s financial condition, real economy, and the crude oil market. Different impacts were observed over time and in response to economic shocks, Results show that the fluctuation of international oil price has a negative impact on our financial condition. Therefore, the government should consider the impact of external shock factors such as international crude oil price when formulating financial policies to prevent financial risks.

PMID:37886766 | PMC:PMC10597845 | DOI:10.1016/j.heliyon.2023.e21085

Heliyon. 2023 Oct 8;9(10):e20613. doi: 10.1016/j.heliyon.2023.e20613. eCollection 2023 Oct.

ABSTRACT

Although the expression of ASPP family members in multiple tumors has been studied, especially in various cell lines of breast cancer (BC), but the expressions pattern of ASPP family members in invasive BC tissues are not clear. We studied the expression and expression pattern of ASPPs family member in BCs, the relationship between ASPP family members and clinic-pathologic features of BCs was also analyzed. The results showed that the expression of ASPP1, ASPP2 and iASPP was observed on AE1/AE3⁺ tumor cells, and not on infiltrated lymphocytes and capillaries. The relationship between ASPP1 expression and pTNM stage has statistical difference (p＜0.01). The relationship between expression of ASPP2 and SBR grade has statistical difference (p＜0.05). The relationship between expression of iASPP and clinic-pathologic feature of patients has no statistical difference (p＞0.05). The patients with positive expression of ASPP1 and the patients with negative expression of ASPP1 have statistical difference in 3-year survival rate and 5-year survival rate (χ² = 4.49, P = 0.03; χ² = 3.79, P = 0.048). Overall, our work demonstrated that the expression of ASPP1/2 contributes to predict the prognosis of patients with BC.

PMID:37886763 | PMC:PMC10597814 | DOI:10.1016/j.heliyon.2023.e20613

Infect Dis Model. 2023 Oct 14;8(4):1127-1137. doi: 10.1016/j.idm.2023.10.002. eCollection 2023 Dec.

ABSTRACT

As most disease causing pathogens require transmission from an infectious individual to a susceptible individual, continued persistence of the pathogen within the population requires the replenishment of susceptibles through births, immigration, or waning immunity. Consider the introduction of an unknown infectious disease into a fully susceptible population where it is not known how long immunity is conferred once an individual recovers from infection. If, initially, the prevalence of disease increases (that is, the infection takes off), the number of infectives will usually decrease to a low level after the first major outbreak. During this post-outbreak period, the disease dynamics may be influenced by stochastic effects and there is a non-zero probability that the epidemic will die out. Die out in this period following the first major outbreak is known as an epidemic fade-out. If the disease does not die out, the susceptible population may be replenished by the waning of immunity, and a second wave may start. In this study, we investigate if the rate of waning immunity (and other epidemiological parameters) can be reliably estimated from multiple outbreak data, in which some outbreaks display epidemic fade-out and others do not. We generated synthetic outbreak data from independent simulations of stochastic SIRS models in multiple communities. Some outbreaks faded-out and some did not. We conducted Bayesian parameter estimation under two alternative approaches: independently on each outbreak and under a hierarchical framework. When conducting independent estimation, the waning immunity rate was poorly estimated and biased towards zero when an epidemic fade-out was observed. However, under a hierarchical approach, we obtained more accurate and precise posterior estimates for the rate of waning immunity and other epidemiological parameters. The greatest improvement in estimates was obtained for those communities in which epidemic fade-out was observed. Our findings demonstrate the feasibility and value of adopting a Bayesian hierarchical approach for parameter inference for stochastic epidemic models.

PMID:37886740 | PMC:PMC10597760 | DOI:10.1016/j.idm.2023.10.002

Bioinform Adv. 2023 Oct 18;3(1):vbad150. doi: 10.1093/bioadv/vbad150. eCollection 2023.

ABSTRACT

SUMMARY: Gene set scoring (or enrichment) is a common dimension reduction task in bioinformatics that can be focused on the differences between groups or at the single sample level. Gene sets can represent biological functions, molecular pathways, cell identities, and more. Gene set scores are context dependent values that are useful for interpreting biological changes following experiments or perturbations. Single sample scoring produces a set of scores, one for each member of a group, which can be analyzed with statistical models that can include additional clinically important factors such as gender or age. However, the sparsity and technical noise of single-cell expression measures create difficulties for these methods, which were originally designed for bulk expression profiling (microarrays, RNAseq). This can be greatly remedied by first applying a smoothing transformation that shares gene measure information within transcriptomic neighborhoods. In this work, we use the nearest neighbor graph of cells for matrix smoothing to produce high quality gene set scores on a per-cell, per-group, level which is useful for visualization and statistical analysis.

AVAILABILITY AND IMPLEMENTATION: The gssnng software is available using the python package index (PyPI) and works with Scanpy AnnData objects. It can be installed using “pip install gssnng.” More information and demo notebooks: see https://github.com/IlyaLab/gssnng.

PMID:37886712 | PMC:PMC10599965 | DOI:10.1093/bioadv/vbad150

Bioinform Adv. 2023 Aug 22;3(1):vbad109. doi: 10.1093/bioadv/vbad109. eCollection 2023.

ABSTRACT

MOTIVATION: Genetic biases in the human antibody repertoire result in publicly available antibody sequence datasets that contain many duplicate or highly similar sequences. Available datasets are further skewed by the predominance of studies focused on specific disease states, primarily cancer, autoimmunity, and a small number of infectious diseases that includes HIV, influenza, and SARS-CoV-2. These biases and redundancies are a barrier to rapid similarity searches and reduce the efficiency with which these datasets can be used to train statistical or machine-learning models. Identity-based clustering provides a solution; however, the extremely large size of available antibody sequence datasets makes such clustering operations computationally intensive and potentially out of reach for many scientists and researchers who would benefit from such data.

RESULTS: Antibody Reference Clusters (AntiRef), which is modeled after UniRef, provides clustered datasets of filtered human antibody sequences. Due to the modular nature of recombined antibody genes, the clustering thresholds used by UniRef for general protein sequences are suboptimal for antibody clustering. Starting with an input dataset of ∼451M full-length, productive human antibody sequences, AntiRef provides reference datasets clustered at a range of antibody-optimized identity thresholds. AntiRef90 is one-third the size of the input dataset and less than half the size of the non-redundant AntiRef100.

AVAILABILITY AND IMPLEMENTATION: AntiRef datasets are available on Zenodo (zenodo.org/record/7474336). All code used to generate AntiRef is available on GitHub (github.com/briney/antiref). The AntiRef versioning scheme (current version: v2022.12.14) refers to the date on which sequences were retrieved from OAS.

PMID:37886711 | PMC:PMC10598580 | DOI:10.1093/bioadv/vbad109

J Pharm Policy Pract. 2023 Oct 27;16(1):128. doi: 10.1186/s40545-023-00638-w.

ABSTRACT

OBJECTIVES: Competencies refer to the knowledge, skills, attitudes, and behaviors individuals develop through education, training, and experience. These competencies can be formulated into a framework to support practitioner development for effective and sustained performance. In the absence of a national framework for pharmacy education and practice in Lebanon, the Order of Pharmacists of Lebanon (OPL, the official association of pharmacists in Lebanon) pioneered the development of a pharmacy competency framework in 2017. This study aimed to validate and assess the specialized competency framework for pharmacists in sales and marketing (SCF-PSM) after updating the framework previously published by the OPL. The secondary objective was to assess, in a pilot survey, the personal characteristics associated with these competencies.

METHODS: After validating the content of the specialized competency framework, a survey involving Lebanese pharmacists was performed through a 15-min online questionnaire distributed over social media platforms, groups of pharmacists, and individual pharmacists’ contact numbers.

KEY FINDINGS: Pharmaceutical knowledge, communication, emergency response, and operation management during emergencies were satisfactory (more than 80/100). Other activities during emergencies, such as patient care and population health interventions and evaluation, research, and dissemination of research outcomes, received a moderate score (75-78/100), similar to legal practice (78/100), teamwork (76/100), and management skills (75/100). The lowest reported confidence was related to professional communication skills (other than communication per se), mainly negotiation, data processing skills, information technology, self-management, and ethical practice (< 75/100). This study reported deficiencies between what is acquired during undergraduate, postgraduate, and continuing education on the one hand and the competency framework suggested by the OPL on the other hand, showing a mismatch between the competencies of working pharmacists acquired during education and the market needs.

CONCLUSIONS: This study validated a competency framework for pharmacists in sales and marketing and explored the current gaps in self-reported competencies. It also identified areas necessitating reinforcement to optimize professional practice and underscored the need for improvement in undergraduate, postgraduate, and continuing professional education.

PMID:37885029 | DOI:10.1186/s40545-023-00638-w

BMC Res Notes. 2023 Oct 26;16(1):295. doi: 10.1186/s13104-023-06568-9.

ABSTRACT

INTRODUCTION: Simultaneous pancreas kidney (SPK) transplantation is an invaluable procedure to enhance the quality of life of insulin-dependent patients with advanced renal disease. The creation of vascular anastomoses of the donor’s pancreas vessels to the recipient’s, is of utmost importance to predict the graft outcome and surgical complications. In the study we introduce a novel technique for arterial reconstruction during SPK transplantation.

METHODS: Conventionally, during the SPK transplantation, a so-called Y-graft is anastomosed between donor’s superior mesenteric and splenic artery to the recipient’s right iliac artery. In the study we adopted a new technique by preparing an extra extension using the donor’s carotid artery, to be anastomosed to the Y-graft and the iliac artery. In this non-blinded randomized clinical trial we compared the surgical complications and early outcomes between the 2 groups of patients with the traditional and new arterial reconstruction techniques during 3 months after transplantation.

RESULTS: Thirty adult patients were included in the study. The incidence of pancreatitis, vascular thrombosis and surgical site infection was lower in the new Y-graft and extension technique, which was not statistically significant. However, the calculated Cohen’s d index showed the medium effect of new Y-graft and extension technique on complication after SPK transplantations.

CONCLUSION: The post-operative complications tend to be lower in the novel arterial reconstruction technique, however a study on a larger patient group is encouraged to confirm our primary results.

TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials on 12/05/2022; IRCT 20210625051701N2; ( http://www.irct.ir/ ).

PMID:37885028 | DOI:10.1186/s13104-023-06568-9

Drug Metab Dispos. 2023 Oct 26:DMD-AR-2023-001500. doi: 10.1124/dmd.123.001500. Online ahead of print.

ABSTRACT

Cytochrome P450 family 1 subfamily A member 2 (CYP1A2), performs an indispensable role in metabolism of both exogenous and endogenous substances. What is more, CYP1A2 functions in human diseases by regulating homeostasis of cholesterol. Despite the emergence of gene-editing animal models, genetically humanized animals that overcome species differences for further exploring the role of CYP1A2 in drug metabolism and human diseases have not yet been constructed. In this study, we inserted human CYP1A2 cDNA into the rat Cyp1a2 gene by using CRISPR/Cas9 technology. Results showed that human CYP1A2 was successfully expressed in humanized rat liver and there were no statistically significant differences of physiological symptoms compared with wild-type (WT) rats. In vitro incubation results indicated the different inhibition of furafylline on CYP1A2 activity in human liver microsomes, humanized CYP1A2 (hCYP1A2) rat liver microsomes, and WT rat liver microsomes, with IC₅₀ values of 7.1 μM, 36.5 μM, and 285.8 μM, respectively. Meanwhile, pharmacokinetic characteristics of clozapine were conducted, and the results suggested that in hCYP1A2 rats, clozapine tended to be metabolized into norclozapine. Both the in vitro and in vivo results demonstrated the different metabolic functions of CYP1A2 in humanized and WT rats. We successfully constructed a novel humanized CYP1A2 rat model using the CRISPR/Cas9 system, providing a powerful tool for better predicting CYP1A2-mediated drug metabolism and pharmacokinetics. Significance Statement Human CYP1A2 takes active part both in the biotransformation of exogenous substances and endogenous substances. Meanwhile, it plays a regulatory role in human diseases, including hypercholesterolemia, hypertension as well as various malignant tumors. This study successfully constructed humanized CYP1A2 rat model by CRISPR/Cas9 technology, providing a powerful model for promoting drug development and safety evaluation, as well as further exploring the role of CYP1A2 in human diseases.

PMID:37884392 | DOI:10.1124/dmd.123.001500

Int J Spine Surg. 2023 Oct 26:8551. doi: 10.14444/8551. Online ahead of print.

ABSTRACT

BACKGROUND: Posterior cervical decompression with or without fusion (PCD/F) is used to manage degenerative spinal conditions. Malnutrition has been implicated for poor outcomes in spine surgery. The aim of this study was to assess the ability of the Geriatric Nutritional Risk Index (GNRI) as a risk calculator for postoperative complications in patients undergoing PCD/F.

METHODS: The 2006 to 2018 American College of Surgeons National Surgery Quality Improvement Program Database was queried for patients undergoing PCD/F. Nutritional status was categorized as normal (GNRI greater than 98), moderately malnourished (GNRI 92-98), or severely malnourished (GNRI less than or equal to 92). Complications within 30 days of surgery were compared among the groups. Preoperative data that were statistically significant (P < 0.05) upon univariate χ² analysis were included in the univariate then multivariate binary regression model to calculate adjusted ORs. All ORs were assessed at the 95% CI.

RESULTS: Of the 7597 PCD/F patients identified, 15.6% were severely malnourished and 19.1% were moderately malnourished. Severe and moderate malnourishment were independent risk factors for mortality (OR = 3.790, 95% CI 2.492-5.763, P < 0.001; OR = 2.150, 95% CI 1.351-3.421, P = 0.011). Severe malnourishment was an independent risk factor for sepsis/septic shock (OR = 3.448, 95% CI 2.402-4.948, P < 0.001).

CONCLUSIONS: In elderly patients undergoing PCD/F, severe malnutrition, as defined by the GNRI, was an independent risk factor for mortality and sepsis/septic shock.

CLINICAL RELEVANCE: The GNRI may be more useful than other indices for risk stratification in elderly patients because it accounts for confounding variables such as hydration status and paradoxical malnourishment in obese patients.

PMID:37884336 | DOI:10.14444/8551

J Orthop Res. 2023 Oct 26. doi: 10.1002/jor.25720. Online ahead of print.

ABSTRACT

Rifampin has been proven to be effective in the treatment of prosthetic infections due to its ability to intercalate into biofilms. The use of rifampin in antibiotic spacers is not well described, which would be especially important in the local periprosthetic environment where parenteral doses have poor penetration. Null hypothesis tests if rifampin use in PMMA cement will show no clinically significant impact on mechanical strength at antibiotic concentrations that remain bactericidal. Test antibiotic cement samples supplemented with 0mg, 30mg, 50mg, 100mg, 150mg or 200mg of rifampin into a standard 40g bag were tested for compression to failure using published ASTM standards. The samples were then inoculated with Pseudomonas aeruginosa and either evaluated for lipo-polysacharide (LPS) presence as a marker of biofilm or tested by elution as the Kirby Bauer assay. Rifampin concentrations of 30mg, and 50mg, showed no statistically different mechanical characteristics to control PMMA (p>0.05). The 100mg sample fell within the acceptable range of compressive strength and had significantly less LPS and bacterial presence compared to control at 12 and 24 hours. The ability of PMMA with 100mg of rifampin to maintain its structural integrity and have significant bacterial inhibition at 12 and 24 hours makes it a great candidate as an antibiotic bone cement additive. PMMA loaded with up to 100mg of rifampin shows promise in the treatment and prevention of PJI for total knee and total hip arthroplasty. This article is protected by copyright. All rights reserved.

PMID:37884321 | DOI:10.1002/jor.25720