Automated surgical planning in spring-assisted sagittal craniosynostosis correction using finite element analysis and machine learning

by Jenson Jacob, Selim Bozkurt

Sagittal synostosis is a condition caused by the fused sagittal suture and results in a narrowed skull in infants. Spring-assisted cranioplasty is a correction technique used to expand skulls with sagittal craniosynostosis by placing compressed springs on the skull before six months of age. Proposed methods for surgical planning in spring-assisted sagittal craniosynostosis correction provide information only about the skull anatomy or require iterative finite element simulations. Therefore, the selection of surgical parameters such as spring dimensions and osteotomy sizes may remain unclear and spring-assisted cranioplasty may yield sub-optimal surgical results. The aim of this study is to develop the architectural structure of an automated tool to predict post-operative surgical outcomes in sagittal craniosynostosis correction with spring-assisted cranioplasty using machine learning and finite element analyses. Six different machine learning algorithms were tested using a finite element model which simulated a combination of various mechanical and geometric properties of the calvarium, osteotomy sizes, spring characteristics, and spring implantation positions. Also, a statistical shape model representing an average sagittal craniosynostosis calvarium in 5-month-old patients was used to assess the machine learning algorithms. XGBoost algorithm predicted post-operative cephalic index in spring-assisted sagittal craniosynostosis correction with high accuracy. Finite element simulations confirmed the prediction of the XGBoost algorithm. The presented architectural structure can be used to develop a tool to predict the post-operative cephalic index in spring-assisted cranioplasty in patients with sagittal craniosynostosis can be used to automate surgical planning and improve post-operative surgical outcomes in spring-assisted cranioplasty.

Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis

by Banghyun Lee, Suk-Joon Chang, Byung Su Kwon, Joo-Hyuk Son, Myong Cheol Lim, Yun Hwan Kim, Shin-Wha Lee, Chel Hun Choi, Kyung Jin Eoh, Jung-Yun Lee, Dong Hoon Suh, Yong Beom Kim

Objectives

This meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on the survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients.

Methods/Materials

A systematic literature search revealed 3,227 studies. A subsequent selection process identified seven suitable randomized studies that assessed the survival outcomes in newly diagnosed advanced EOC patients administered PARPi (n = 1921; the PARPi group) or placebo (n = 1150; the placebo group). The survival outcomes were compared with respect to the PARPi treatment regardless of bevacizumab maintenance therapy. All adverse events ≥ grade 3 were analyzed. Review Manager Version 5.4.1 software was used for the meta-analysis.

Results

The two-year progression-free survival (PFS) was significantly better in the PARPi group than the placebo (Hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41 to 0.68). Furthermore, patients in the PARPi group with the BRCA1/2 mutation (BRCAm), BRCA wild type, homologous-recombination deficiency (HRD), or HRD without BRCAm, but not with homologous-recombination proficiency had a significantly better two-year PFS than the patients in the placebo group. The five-year overall survival (OS) was comparable in the two groups, but patients in the PARPi group with BRCAm had a significantly better five-year OS than those in the placebo group (HR, 0.57; 95% CI, 0.44 to 0.74). In addition, the adverse event rate (≥ grade 3) was significantly higher in the PARPi group than in the placebo group (HR, 2.94; 95% CI, 1.13 to 7.63).

Conclusions

In patients with newly diagnosed advanced EOC, PARPi maintenance therapy was significantly more effective in terms of survival than no PARPi treatment. However, the risk of serious adverse events was higher for patients who received PARPi maintenance therapy.

Factors associated with infant mortality in Nigeria: A scoping review

by Loveth Dumebi Nwanze, Alaa Siuliman, Nuha Ibrahim

Background

Infant mortality persists as a global public health concern, particularly in lower-middle-income countries (LIMCs) such as Nigeria. The risk of an infant dying before one year of age is estimated to be six times higher in Africa than in Europe. Nigeria recorded an infant mortality rate of 72.2 deaths per 1,000 live births in 2020, in contrast to the global estimate of 27.4 per 1,000 live births. Several studies have been undertaken to determine the factors influencing infant mortality.

Objective

This scoping review sought to identify and summarise the breadth of evidence available on factors associated with infant mortality in Nigeria.

Methods

This review followed the five-stage principles of Arksey and O’Malley’s framework. Four electronic databases were searched with no limit to publication date or study type: Ovid MEDLINE, PubMed, CINAHL Complete, and Web of Science. Selected studies were imported into Endnote software and then exported to Rayyan software where duplicates were removed. Included articles were thematically analysed and synthesised using the socioecological model.

Results

A total of 8,139 references were compiled and screened. Forty-eight articles were included in the final review. At the individual level, maternal- and child-related factors were revealed to influence infant mortality; socioeconomic and sociocultural factors at the interpersonal level; provision and utilisation of health services, health workforce, hospital resources and access to health services at the organisational level; housing/neighbourhood and environmental factors at the community level; and lastly, governmental factors were found to affect infant mortality at the public policy level.

Conclusion

Factors related to the individual, interpersonal, organisational, community and public policy levels were associated with infant mortality in Nigeria.

In silico exploration of <i>Serratia</i> sp. BRL41 genome for detecting prodigiosin Biosynthetic Gene Cluster (BGC) and in vitro antimicrobial activity assessment of secreted prodigiosin

by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar

The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.

Prevalence and clinical implications of respiratory viruses in asthma during stable disease state and acute attacks: Protocol for a meta-analysis

by Gioulinta S. Alimani, Sachin Ananth, Cristina Boccabella, Ekaterina Khaleva, Graham Roberts, Nikolaos G. Papadopoulos, Chris Kosmidis, Jørgen Vestbo, Effie Papageorgiou, Apostolos Beloukas, Alexander G. Mathioudakis

Introduction

Viruses are detected in over 50% of acute asthma attacks and in a notable proportion of patients with asthma during stable disease state They are associated with worse outcomes. We will conduct a series of systematic reviews and meta-analyses to quantify the prevalence and clinical burden of various respiratory viruses in stable asthma and acute asthma attacks. In addition, we will assess the viral loads of respiratory viruses during stable and acute asthma, to explore whether viral load could differentiate attacks triggered by viruses versus those where viruses are present as “innocent bystanders”.

Materials and methods

Based on a prospectively registered protocol (PROSPERO, ID: CRD42023375108) and following standard methodology recommended by Cochrane, we will systematically search Medline/PubMed, EMBASE, the Cochrane Library and relevant conference proceedings for studies assessing the prevalence or clinical burden of respiratory viruses in asthma. Methodological rigour of the included studies will be appraised using a tool specific for prevalence studies and the Newcastle-Ottawa Scale respectively. In anticipation of significant clinical and methodological heterogeneity, we will conduct random effect meta-analyses. For evaluating the prevalence of viruses, we will perform meta-analyses of proportions using the inverse variance method, and the Freeman-Tukey transformation. We will conduct meta-regression analyses for exploring heterogeneity.

Conclusion

We envisage that these systematic reviews and meta-analyses will quantify the prevalence and burden of respiratory viruses in stable and acute asthma and will drive future research and clinical practice.