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The advent of digitalization has been hailed as a remedy to mitigate the impact of the Covid-19 pandemic. However, it has also brought to light the existence of a digital divide, exacerbating the hardships faced by those who are digitally excluded. Amidst the turmoil of the crisis, there has been limited attention given to addressing the digital divide in developing countries including Malaysia. In response, Malaysian universities swiftly transitioned to online learning to curb the spread of the contagion. Nonetheless, this rapid shift has inadvertently marginalized underprivileged students, hindering their access to the benefits of online education. Employing the three-level digital divide framework, this study aims to probe into the extent of the digital divide among Malaysian university students and evaluate its progression. Through mean score and frequency analyses, we assessed the magnitude of the digital divide among these students. Furthermore, we employed partial least squares structural equation modeling to gauge the flow of the digital divide from the initial level to the third level. Subsequently, we examined the mediating roles of material access, digital skills, and digital usage. The findings revealed that the digital divide persists across all three levels among university students in Malaysia. The path analysis lends support to all proposed hypotheses, with the exception of digital usage as a predictor of student satisfaction and as a mediator.

To ensure sustainable development, there is a limit to the extent of urbanization. Thus, rural development is an essential strategy that many nations must work on to ensure optimal economic, environmental, and social outcomes at a country level. However, rural development in itself is challenging because rural communities typically have limited resources and capabilities to address common livelihood challenges, let alone take on new economic roles. Hence, as part of rural revitalization strategies, innovation plays a critical role. A wide range of technologies can facilitate innovation in rural development, including the internet and new agricultural technologies. In addition, new mindsets and shifts in values, such as the changing trends of work and consumerism, can create opportunities for rural areas to adopt innovation and develop new growth engines. However, it should be noted that the nature of innovation in rural and urban settings are different. In rural regions, growth could be enabled through more specific types of innovations, including frugal innovation, inclusive innovation, and social innovation. To enable these forms of innovations in rural areas, this paper proposes a three-dimensional process model that includes pro-social technological innovation policy, rural innovation governance, and dynamic networks that close the gap between rural and urban innovation systems. Examples from China, such as the development of Tengtou Village and Taobao Villages serve to demonstrate these concepts. Overall, the discussions in the paper suggest that to enable innovation in rural development, it is necessary to foster closer interactions between rural and urban innovation ecosystems for the former to leverage the latter’s technologies, networks, and resources.

The advancement of nanotechnology has had an impact on the use of heat exchangers. Nanocoolants, which offer higher thermal efficiency than traditional coolants, have paid significant attention. These innovative fluids, which contain nanomaterials, not only have better heat efficiency but also improve energy efficiency compared to regular coolants. However, the presence of solid nanoparticles in the coolant may cause corrosion and erosion of tubes, leading to massive degradation of those parts. To evaluate the effectiveness of nanocoolant particles, this research was conducted by studying the impact of using nanocoolant on erosion-corrosion occurring on metal surfaces. The study focused on the erosion-corrosion of stainless steel (AISI 316) in coolant solutions containing nanoparticles. The experiments utilized a rotating cylinder electrode (RCE) with rotational speeds ranging from 0 to 1800 rpm and a temperature range of 30°C-70°C. The corrosion rate was determined using the linear polarization resistance (LPR) method, while the erosion was measured by calculating the average surface roughness of the samples. The design of the experiment (DOE) was utilized to find the mathematical expressions of the effects of the nanocoolant on erosion and corrosion. The findings revealed that the corrosion rate and surface roughness of the samples increased with an increase in temperature and rotation speed. Furthermore, the erosion-corrosion effects of the nanocoolant were less significant in stagnant conditions than in flow conditions, and significant differences were observed when compared with conventional coolant. Additionally, synergistic erosion and corrosion processes were detected at higher temperatures and higher rotation speeds for both types of coolants.

ABSTRACT In a recent household transmission study of SARS-CoV-2, we found extreme differences in SARS-CoV-2 viral loads among paired saliva, anterior nares swab (ANS), and oropharyngeal swab specimens collected from the same time point. We hypothesized these differences may hinder low-analytical-sensitivity assays (including antigen rapid diagnostic tests [Ag-RDTs]) by using a single specimen type (e.g., ANS) from reliably detecting infected and infectious individuals. We evaluated daily at-home ANS Ag-RDTs (Quidel QuickVue) in a cross-sectional analysis of 228 individuals and a longitudinal analysis (throughout infection) of 17 individuals enrolled early in the course of infection. Ag-RDT results were compared to reverse transcription-quantitative PCR (RT-qPCR) results and high, presumably infectious viral loads (in each, or any, specimen type). The ANS Ag-RDT correctly detected only 44% of time points from infected individuals on cross-sectional analysis, and this population had an inferred limit of detection of 7.6 × 106 copies/mL. From the longitudinal cohort, daily Ag-RDT clinical sensitivity was very low (

Callogenesis and embryogenesis are integral parts of many tissue culture procedures for genetic manipulation in rice. However, the efficiency of both processes is largely dependent on the media constituent especially the plant growth regulators (PGRs) due to the genotype-dependent nature of in vitro culture protocols. Therefore, this study investigates the effect of two PGRs; 2, 4-dichlorophenoxyacetic acid (2, 4-D) and kinetin (Kin) on callus growth and somatic embryogenesis of an important Malaysian rice cultivar (Oryza sativa L. cv. MARDI Siraj 297). Mature rice seeds explants were inoculated in Murashige & Skoog (MS) medium supplemented with different combinations of 2, 4-D (0 to 3.5 mg/L) and Kin (0 to 0.5 mg/L) to induce callogenesis. Parameters for callus growth such as fresh weight (FW), callus induction frequency (CIF), embryogenic callus frequency (ECF), regeneration frequency (RF), number of plantlets per callus (PPC), callus texture and callus color were observed after 35 days of inoculation. The results show that the maximum callus growth was achieved in MS medium supplemented with combination of 2.0 mg/L 2, 4-D and 0.2 mg/L Kin, represented by the highest FW (211 mg), CIF (95%), ECF (90%), RF (100%) and PPC (22 plantlets); along with friable callus texture. Low concentration of 2, 4-D (0 to 0.5 mg/L) in the presence or absence of Kin promotes root growth instead of callus, while high concentrations (above 3.0 mg/L) retard the callus formation. The embryogenic calli from this optimized PGRs combination were successfully formed shoots in MS medium supplemented with 2 mg/L BAP and 1 mg/L NAA, followed by rooting in PGRs-free MS medium. This finding provides an efficient protocol for callogenesis and somatic embryogenesis of MARDI Siraj 297, since this is the first published report regarding somatic embryogenesis induction of this cultivar.

Microbially induced carbonate precipitation by ureolysis is a biomineralization process that has been adapted by various microorganisms in different natural environments. This widespread natural phenomenon can be employed in numerous civil engineering and soil stabilization applications. In the present study, the potential of indigenous soil urease-producing bacteria as potential agents for soil stabilization methods was investigated. Assessment of the eight active urease-producing bacterial species isolated from the farm soil samples has demonstrated that all the isolates were Gram-positive rod-shaped bacteria with promising characteristics such as the formation of endospore which is essential for bacterial survival in harsh conditions within the soil environment. The pH profile and growth profile of the isolates were studied and urease activity was measured by the phenol hypochlorite assay method. Two isolates designated isolate O6w and isolate O3a were selected based on the highest urease activity recorded at 665 U/mL and 620 U/mL, respectively, and they were able to increase and sustain alkaline culture condition (pH 8.71 ± 0.01 and 8.55 ± 0.01) which was suitable for CaCO3 precipitation. The isolates were identified based on 16S ribosomal RNA sequencing to be Bacillus cereus (O6w) and Bacillus paramycoides (O3a). This current study suggested that indigenous soil ureolytic bacteria are potential raw material for the biotreatment of soils stability.

A common practice to enhance seed quality for direct seeding of rice is priming under unfavorable designated conditions. This study aims to increase germination performance and early seedling growth of the MR219 rice by determining optimum priming times and ideal concentrations of gibberellic acid (GA3). Seeds were primed with GA3 in concentrations ranging from 20, 40, 60, 80 and 100 mg/L for 12 and 18 hours separately, and unprimed seeds served as control. The germination test was measured using a completely randomized design (CRD); meanwhile, pot cultivation was carried out using a randomized complete block design (RCBD) for four weeks. In germination studies, it was found that seeds primed with GA3 for 12 hours at 60 mg/L significantly enhanced the germination performance, and early seedling growth of MR219 compared to unprimed seeds. The primed seeds had a germination percentage between 90-100%, increased seed vigor and germination indexes 3-fold and 2-fold respectively, and reduced the mean germination time by 24 hours. Correspondingly, in pot cultivation, the establishment and early seedling growth of primed MR219 was significantly increased as the seedling height, and total fresh weight was two times higher than unprimed seedlings. In addition, the biochemical attributes of GA3 primed seedlings, including total soluble sugar, carbohydrate, and total soluble protein, were significantly increased by 2-, 1.6- and 4-folds, respectively, compared to unprimed seedlings. Priming MR219 seeds with GA3 at 60 mg/L for 12 hours was found to significantly enhance the germination performance and early seedling growth in pot cultivation of direct-seeded rice as it promoted vigorous seedling growth of the MR219 rice cultivar.

In the clinic, most cases of congenital heart valve defects are thought to arise through errors that occur after the endothelial-mesenchymal transition (EndoMT) stage of valve development. Although mechanical forces caused by heartbeat are essential modulators of cardiovascular development, their role in these later developmental events is poorly understood. To address this question, we used the zebrafish superior atrioventricular valve (AV) as a model. We found that cellularized cushions of the superior atrioventricular canal (AVC) morph into valve leaflets via mesenchymal-endothelial transition (MEndoT) and tissue sheet delamination. Defects in delamination result in thickened, hyperplastic valves, and reduced heart function. Mechanical, chemical, and genetic perturbation of cardiac forces showed that mechanical stimuli are important regulators of valve delamination. Mechanistically, we show that forces modulate Nfatc activity to control delamination. Together, our results establish the cellular and molecular signature of cardiac valve delamination in vivo and demonstrate the continuous regulatory role of mechanical forces and blood flow during valve formation.

This study described the production method of novel whiskey using black pepper berries as raw material including the determination of chemical composition and sensory profile of this distillate. The production process consisted of production of fermentation medium via hydrothermal treatment, followed by fermentation and distillation. The incorporation of hydrothermal extraction process makes this whiskey production process differ from the existing commercial spirit production protocol. Chemical composition analysis showed that there were 12 main volatile compounds that contribute to the aroma profile of this pepper whiskey which consisted of 1 aldehyde group, 3 ester groups, 2 phenolic compounds, and 6 alcohol groups. All of these compounds are presented at different concentrations that are able to give pleasant and signature aroma to this spirit. A 10-member descriptive analysis panel conducted showed that 7 descriptors can be used to define the organoleptic quality of this whiskey, namely, clarity and brilliance (visual), fruity and flora (aroma), spiciness and sweetness (taste), and fruity mouthfeels. In conclusion, pepper berries can be used as raw material for pepper whiskey production and having organoleptic quality acceptable for human consumption.

Objective To evaluate the effectiveness of the upgraded eCARE monitoring system on asthma control in discharged emergency department (ED) patients.Methods A multicentre randomised controlled study (randomised controlled trial) was done for patients with a primary diagnosis of asthma seen at the EDs in Singapore between 1 March 2013 and 28 February 2015. Those who met the inclusion criteria were randomised into a control group (routine care, n=212) and intervention group (eCARE, n=212). Patients in the intervention group received short message service (SMS) messages according to a structured workflow, while patients in the control group did not receive SMS support.Results For patients with poorly controlled asthma at recruitment, the results at 5 weeks showed no statistical difference in the proportion of patients who attained well-controlled asthma between the eCARE and routine care groups. At 3 months, the routine care group had a higher proportion of patients with well-controlled asthma but this was not statistically significant after adjustment for baseline differences using logistic regression. Approximately 95% of patients under the eCARE programme were satisfied with the SMS service.Discussion Patients in the eCARE programme did not have better asthma control than those receiving routine care. Conversely, patients in the eCARE programme appeared to have poorer asthma control, though a larger sample size will be required to confirm this finding.

Background Prosthesis-patient mismatch (PPM) is characterised by the effects of inadequate prosthesis size relative to body surface area (BSA). It is uncertain whether PPM after mitral valve replacement impacts upon clinical outcome. This was examined in an Australian population. Methods From 2001 to 2009, 1006 mechanical and bioprosthetic mitral valves were implanted across 10 institutions. Effective orifice areas (EOA) were obtained from a literature review of in vivo echocardiographic data. Absent, moderate and severe PPM was defined as an indexed EOA (EOA/BSA) of >1.20cm(2)/m(2), >0.90 to <=1.20cm(2)/m(2) and <=0.9cm(2)/m(2), respectively. Early outcomes and 7-year survival were compared between these three groups. Results PPM was absent in 34%, moderate in 53% and severe in 13% of patients. Patients with PPM were more likely to be male (42% vs 52% vs 62%, p<0.0001) and obese (14% vs 20% vs 56%, p<0.0001). Postoperatively there was similar 30-day mortality (5% vs 5% vs 6%, p=0.83) and early any mortality/morbidity (24% vs 27% vs 29%, p=0.40). Seven-year survival was similar between groups (72±4.1% vs 76±3.2% vs 69±10.3%, p=0.76). PPM did not predict adverse events after logistic and Cox regressions with and without propensity score adjustment. Subgroup analyses of those with isolated mitral valve surgery, patients with preoperative congestive heart failure and non-obese patients failed to show an association between PPM and mid-term mortality. Conclusions Overall, PPM was not associated with poorer early outcomes or mid-term survival. Oversizing valves may be technically hazardous and do not yield superior outcomes. Easier implantation by appropriate sizing appears justified. [ABSTRACT FROM AUTHOR]

Over the last few decades, the excess exploitation of our planet and degradation of environment have gone up at an alarming rate. Environmental problems, especially air and water pollution, which takes a huge number of years to recover, have become the major concern affecting the progress of human society. The overwhelming threats have driven global research and innovation in the development of advanced technology and devices toward a cleaner environment. In this context, the generation of functional one-dimensional (1-D) nanomaterials has become an area of intense interest from both academia and industry due to their unique advantages for environmental applications. Electrospinning is recognized as the most powerful technique for producing 1-D composite nanofibers via facile incorporation of active ingredients in the solutions for electrospinning or by some posttreatment process. In this review, we give an overview on the latest research progress in the fabrication and utilization of functional polymer/ceramic/carbon nanofibers generated by electrospinning for air and water purification, as well as their applications as sensors for pollutant monitoring and control. We also present the perspectives and challenges of the current electrospinning technique for environmental applications.

Amaranth is a very important vegetable worldwide. Its leaves are consumed and the seeds are processed into various food products. Its production in the tropics is threatened by low yields which has a major impact on global production. A research aimed at improving the yield of this vegetable was carried out at lady bird organic farm Broga, 2.9450N 101.8740E, Semenyih, Selangor, Malaysia by studying the effect of genotype and organic fertilizer on the following growth indicators, red:far red ratio below canopy, stomatal conductance, leaf temperature, and dry weight. These growth indicators were monitored on a weekly basis over a period of six weeks. Three genotypes namely, Amaranthus caudatus, 3388 (green round leaf), Amaranthus caudatus, 3233 (green long leaf) and Amaranthus cruentus, 888 (red leaf) were grown on soils to which organic fertilizer was added at three different application rates (0 t/ha, 7.5 t/ha and 15 t/ha). There was no significant interaction effect of genotype and organic fertilizer on the growth indicators; however, each of these factors had significant effect on the growth of amaranth. A strong negative correlation occurred between dry weight and red:far red ratio below canopy likewise, between stomatal conductance and leaf temperature. Over a cultivation period of five weeks, the green long leaf genotype was superior showing that it is better adapted to growing in the rainforest agro ecological zone of Malaysia than the other two genotypes. Organic fertilizer application at a rate of 15 t/ha produced the lowest leaf temperature, after 4 weeks of cultivation implying better water status than 0 t/ha and 7.5 t/ha application rates. This study clearly shows that genotype and organic fertilizer have significant effect on the growth of amaranth. Therefore, these factors can be manipulated in order to enhance amaranth production.

Obesity and rates of non-communicable diseases linked to physical inactivity have increased dramatically in Malaysia over the past 20 years. Malaysia has also been identified as one of the least physically active countries in the world with over 60% of adults being essentially sedentary. This study examines the relationship of socio-demographic factors to physical activity among 770 adults from 3 Malaysian states. Physical activity levels were significantly related to ethnicity, gender, age, occupation and educational level. Controlling for inter-relationships among these variables; age, gender, Chinese ethnicity and education level were found to have unique effects on total physical activity, as well as moderate and vigorous exercise. As would be expected, younger people were more physically active, engaging more in both moderate and vigorous types of exercise and males were generally more active than females. Contrary to findings from many developed countries, however, more educated Malaysians were less likely to engage in all types of physical activity. Ethnic Chinese participants, and to a lesser degree Indians also consistently reported lower levels of activity. Possible intervention strategies are discussed that specifically target ethnic and cultural norms related to physical activity. Future research programs exploring barriers to participation and perceptions of physical activity, as well as programs to encourage active life styles among youths are also suggested.

As indicated by the World Health Organization as of year 2014, around 10,000 people have been influenced with Ebola infection. The episode of Ebola in African locale is courged with a high death rate. Notwithstanding, in the United States, people influenced by Ebola have been given brilliant wellbeing offices, as the U.S. is one of the highest nations that have taken sterner wellbeing measures and principles against Ebola. Aside from the U.S., individuals in Asia, where billions live in indigence and general wellbeing frameworks are frequently extremely powerless, are under more serious danger of the Ebola infection. Despite the fact that nations like Singapore, Malaysia, South Korea and Japan can take stretched out measures to battle against the infection, nations like Philippines and Indonesia have unfathomable quantities of poor who may be incredibly influenced by a conceivable episode. At this moment, the chances that Asia will take a critical hit from the Ebola infection appear to be genuinely little. Yet, while it is far-fetched that Asia will encounter a real flare-up, genuine concerns stay about the infection coming to urban communities like Hong Kong, Beijing, Shanghai and Singapore through their worldwide airplane terminals. Wellbeing priests from the Association of Southeast Asian Nations (ASEAN) reported key measures not long ago to keep the Ebola plague from coming to the locale and to backing influenced nations. This article accordingly will concentrate on the prevalence and current approaches of Ebola Virus Disease in ASEAN nations which is the need of the hour.

A randomized complete block (RCBD) study was designed to investigate the effects of cadmium (Cd) and copper (Cu) on the growth, bioaccumulation of the two heavy metals, metabolite content and antibacterial activities in Gyanura procumbens (Lour.) Merr. Nine treatments including (1) control (no Cd and Cu); (2) Cd 2 = cadmium 2 mg/L; (3) Cd 4 = cadmium 4 mg/L; (4) Cu 70 = copper 70 mg/L; (5) Cu 140 = copper 140 mg/L); (6) Cd 2 + Cu 70 = cadmium 2 mg/L + copper 70 mg/L); (7) Cd 2 + Cu 140 = cadmium 2 mg/L + copper 70 mg/L); (8) Cd 4 + Cu 70 = cadmium 4 mg/L+ copper 70 mg/L and (9) Cd 4 + Cu 140 = cadmium 4 mg/L + copper 140 mg/L) were evaluated in this experiment. It was found that the growth parameters (plant dry weight, total leaf area and basal diameter) were reduced with the exposure to increased concentrations of Cd and Cu and further decreased under interaction between Cd and Cu. Production of total phenolics, flavonoids and saponin was observed to be reduced under combined Cd and Cu treatment. The reduction in the production of plant secondary metabolites might be due to lower phenyl alanine lyase (PAL) activity under these conditions. Due to that, the 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP) and antibacterial activities was also found to be reduced by the combined treatments. The current experiments show that the medicinal properties of G. procumbens are reduced by cadmium and copper contamination. The accumulation of heavy metal also was found to be higher than the safety level recommended by the WHO in the single and combined treatments of Cd and Cu. These results indicate that exposure of G. procumbens to Cd and Cu contaminated soil may potentially harm consumers due to bioaccumulation of metals and reduced efficacy of the herbal product.

Our previous study shows that inhibiting activator protein one (AP1) transcription factor function in murine epidermis, using dominant-negative c-jun (TAM67), increases cell proliferation and delays differentiation. To understand the mechanism of action, we compare TAM67 impact in mouse epidermis and in cultured normal human keratinocytes. We show that TAM67 localizes in the nucleus where it forms TAM67 homodimers that competitively interact with AP1 transcription factor DNA binding sites to reduce endogenous jun and fos factor binding. Involucrin is a marker of keratinocyte differentiation that is expressed in the suprabasal epidermis and this expression requires AP1 factor interaction at the AP1-5 site in the promoter. TAM67 interacts competitively at this site to reduce involucrin expression. TAM67 also reduces endogenous c-jun, junB and junD mRNA and protein level. Studies with c-jun promoter suggest that this is due to reduced transcription of the c-jun gene. We propose that TAM67 suppresses keratinocyte differentiation by interfering with endogenous AP1 factor binding to regulator elements in differentiation-associated target genes, and by reducing endogenous c-jun factor expression.

Abstract Background While there is strong evidence for phosphatidylinositol 3-kinase (PI3K) involvement in cancer development, there is limited information about the role of PI3K regulatory subunits. PIK3R3, the gene that encodes the PI3K regulatory subunit p55γ, is over-expressed in glioblastoma and ovarian cancers, but its expression in gastric cancer (GC) is not known. We thus used genetic and bioinformatic approaches to examine PIK3R3 expression and function in GC, the second leading cause of cancer mortality world-wide and highly prevalent among Asians. Methods Primary GC and matched non-neoplastic mucosa tissue specimens from a unique Asian patient gastric cancer library were comprehensively profiled with platforms that measured genome-wide mRNA expression, DNA copy number variation, and DNA methylation status. Function of PIK3R3 was predicted by IPA pathway analysis of co-regulated genes with PIK3R3, and further investigated by siRNA knockdown studies. Cell proliferation was estimated by crystal violet dye elution and BrdU incorporation assay. Cell cycle distribution was analysed by FACS. Results PIK3R3 was significantly up-regulated in GC specimens (n = 126, p Conclusion Using a combination of genetic, bioinformatic, and molecular biological approaches, we showed that PIK3R3 was up-regulated in GC and promoted cell cycle progression and proliferation; and thus may be a potential new therapeutic target for GC.

Abstract Background Product risk management involves critical assessment of the risks and benefits of health products circulating in the market. One of the important sources of safety information is the primary literature, especially for newer products which regulatory authorities have relatively little experience with. Although the primary literature provides vast and diverse information, only a small proportion of which is useful for product risk assessment work. Hence, the aim of this study is to explore the possibility of using text mining to automate the identification of useful articles, which will reduce the time taken for literature search and hence improving work efficiency. In this study, term-frequency inverse document-frequency values were computed for predictors extracted from the titles and abstracts of articles related to three tumour necrosis factors-alpha blockers. A general automated system was developed using only general predictors and was tested for its generalizability using articles related to four other drug classes. Several specific automated systems were developed using both general and specific predictors and training sets of different sizes in order to determine the minimum number of articles required for developing such systems. Results The general automated system had an area under the curve value of 0.731 and was able to rank 34.6% and 46.2% of the total number of 'useful' articles among the first 10% and 20% of the articles presented to the evaluators when tested on the generalizability set. However, its use may be limited by the subjective definition of useful articles. For the specific automated system, it was found that only 20 articles were required to develop a specific automated system with a prediction performance (AUC 0.748) that was better than that of general automated system. Conclusions Specific automated systems can be developed rapidly and avoid problems caused by subjective definition of useful articles. Thus the efficiency of product risk management can be improved with the use of specific automated systems.

Abstract Background Currently, there are no standard guidelines for recommending re-administration of a chemotherapeutic drug to a patient after a serious adverse drug reaction (ADR) incident. The decision on whether to rechallenge the patient is based on the experience of the clinician and is highly subjective. Thus the aim of this study is to develop a decision support tool to assist clinicians in this decision making process. Methods The inclusion criteria for patients in this study are: (1) had chemotherapy at National Cancer Centre Singapore between 2004 to 2009, (2) suffered from serious ADRs, and (3) were rechallenged. A total of 46 patients fulfilled the inclusion criteria. A genetic algorithm attribute selection method was used to identify clinical predictors for patients' rechallenge status. A Naïve Bayes model was then developed using 35 patients and externally validated using 11 patients. Results Eight patient attributes (age, chemotherapeutic drug, albumin level, red blood cell level, platelet level, abnormal white blood cell level, abnormal alkaline phosphatase level and abnormal alanine aminotransferase level) were identified as clinical predictors for rechallenge status of patients. The Naïve Bayes model had an AUC of 0.767 and was found to be useful for assisting clinical decision making after clinicians had identified a group of patients for rechallenge. A platform independent version and an online version of the model is available to facilitate independent validation of the model. Conclusion Due to the limited size of the validation set, a more extensive validation of the model is necessary before it can be adopted for routine clinical use. Once validated, the model can be used to assist clinicians in deciding whether to rechallenge patients by determining if their initial assessment of rechallenge status of patients is accurate.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but it could also significantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV., (© 2024. The Author(s).)

Finite Element simulations are a robust way of investigating cardiac biomechanics. To date, it has only been performed with the left ventricle (LV) alone for fetal hearts, even though results are likely different with biventricular (BiV) simulations. In this research, we conduct BiV simulations of the fetal heart based on 4D echocardiography images to show that it can capture the biomechanics of the normal healthy fetal heart, as well as those of fetal aortic stenosis better than the LV alone simulations. We found that performing LV alone simulations resulted in overestimation of LV stresses and pressures, compared to BiV simulations. Interestingly, inserting a compliance between the LV and right ventricle (RV) in the lumped parameter model of the LV only simulation effectively resolved these overestimations, demonstrating that the septum could be considered to play a LV-RV pressure communication role. However, stresses and strains spatial patterns remained altered from BiV simulations after the addition of the compliance. The BiV simulations corroborated previous studies in showing disease effects on the LV, where fetal aortic stenosis (AS) drastically elevated LV pressures and reduced strains and stroke volumes, which were moderated down with the addition of mitral regurgitation (MR). However, BiV simulations enabled an evaluation of the RV as well, where we observed that effects of the AS and MR on pressures and stroke volumes were generally much smaller and less consistent. The BiV simulations also enabled investigations of septal dynamics, which showed a rightward shift with AS, and partial restoration with MR. Interestingly, AS tended to enhance RV stroke volume, but MR moderated that down., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fluid dynamics computations for tube-like geometries are crucial in biomedical evaluations of vascular and airways fluid dynamics. Physics-Informed Neural Networks (PINNs) have emerged as a promising alternative to traditional computational fluid dynamics (CFD) methods. However, vanilla PINNs often demand longer training times than conventional CFD methods for each specific flow scenario, limiting their widespread use. To address this, multi-case PINN approach has been proposed, where varied geometry cases are parameterized and pre-trained on the PINN. This allows for quick generation of flow results in unseen geometries. In this study, we compare three network architectures to optimize the multi-case PINN through experiments on a series of idealized 2D stenotic tube flows. The evaluated architectures include the 'Mixed Network', treating case parameters as additional dimensions in the vanilla PINN architecture; the "Hypernetwork", incorporating case parameters into a side network that computes weights in the main PINN network; and the "Modes" network, where case parameters input into a side network contribute to the final output via an inner product, similar to DeepONet. Results confirm the viability of the multi-case parametric PINN approach, with the Modes network exhibiting superior performance in terms of accuracy, convergence efficiency, and computational speed. To further enhance the multi-case PINN, we explored two strategies. First, incorporating coordinate parameters relevant to tube geometry, such as distance to wall and centerline distance, as inputs to PINN, significantly enhanced accuracy and reduced computational burden. Second, the addition of extra loss terms, enforcing zero derivatives of existing physics constraints in the PINN (similar to gPINN), improved the performance of the Mixed Network and Hypernetwork, but not that of the Modes network. In conclusion, our work identified strategies crucial for future scaling up to 3D, wider geometry ranges, and additional flow conditions, ultimately aiming towards clinical utility., (© 2024. The Author(s).)

Introduction: Ejection fraction (EF) is widely used to evaluate heart function during heart failure (HF) due to its simplicity compared but it may misrepresent cardiac function during ventricular hypertrophy, especially in heart failure with preserved EF (HFpEF). To resolve this shortcoming, we evaluate a correction factor to EF, which is equivalent to computing EF at the mid-wall layer (without the need for mid-layer identification) rather than at the endocardial surface, and thus better complements other complex metrics., Method: The retrospective cohort data was studied, consisting of 2,752 individuals (56.5% male, age 69.3 ± 16.4 years) admitted with a request of a troponin test and undergoing echocardiography as part of their clinical assessment across three centres. Cox-proportional regression models were constructed to compare the adjusted EF (EFa) to EF in evaluating risk of heart failure admissions., Result: Comparing HFpEF patients to non-HF cases, there was no significant difference in EF (62.3 ± 7.6% vs. 64.2 ± 6.2%, p  = 0.79), but there was a significant difference in EFa (56.6 ± 6.4% vs. 61.8 ± 9.9%, p  = 0.0007). Both low EF and low EFa were associated with a high HF readmission risk. However, in the cohort with a normal EF (EF ≥ 50%), models using EFa were significantly more associative with HF readmissions within 3 years, where the leave one out cross validation ROC analysis showed a 18.6% reduction in errors, and Net Classification Index (NRI) analysis showed that risk increment classification of events increased by 12.2%, while risk decrement classification of non-events decreased by 16.6%., Conclusion: EFa is associated with HF readmission in patients with a normal EF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Chan, Kaura, Mulla, Papadimitriou, Glampson, Mayer, Shah, Mayet and Yap.)

Cardiac ultrasound (US) image segmentation is vital for evaluating clinical indices, but it often demands a large dataset and expert annotations, resulting in high costs for deep learning algorithms. To address this, our study presents a framework utilizing artificial intelligence generation technology to produce multi-class RGB masks for cardiac US image segmentation. The proposed approach directly performs semantic segmentation of the heart's main structures in US images from various scanning modes. Additionally, we introduce a novel learning approach based on conditional generative adversarial networks (CGAN) for cardiac US image segmentation, incorporating a conditional input and paired RGB masks. Experimental results from three cardiac US image datasets with diverse scan modes demonstrate that our approach outperforms several state-of-the-art models, showcasing improvements in five commonly used segmentation metrics, with lower noise sensitivity. Source code is available at https://github.com/energy588/US2mask., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre-FAV image-based computations could robustly distinguish between CAS-eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image-based finite element biomechanics modelling of nine CAS-eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS-eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes. KEY POINTS: Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions. Computational simulations show that a biomechanics parameter, pre-intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters. An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Cardiac trabeculae are uneven ventricular muscular structures that develop during early embryonic heart development at the outer curvature of the ventricle. Their biomechanical function is not completely understood, and while their formation is known to be mechanosensitive, it is unclear whether ventricular tissue internal stresses play an important role in their formation. Here, we performed imaging and image-based cardiac biomechanics simulations on zebrafish embryonic ventricles to investigate these issues. Microscopy-based ventricular strain measurements show that the appearance of trabeculae coincided with enhanced deformability of the ventricular wall. Image-based biomechanical simulations reveal that the presence of trabeculae reduces ventricular tissue internal stresses, likely acting as structural support in response to the geometry of the ventricle. Passive ventricular pressure-loading experiments further reveal that the formation of trabeculae is associated with a spatial homogenization of ventricular tissue stiffnesses in healthy hearts, but gata1 morphants with a disrupted trabeculation process retain a spatial stiffness heterogeneity. Our findings thus suggest that modulating ventricular wall deformability, stresses, and stiffness are among the biomechanical functions of trabeculae. Further, experiments with gata1 morphants reveal that a reduction in fluid pressures and consequently ventricular tissue internal stresses can disrupt trabeculation, but a subsequent restoration of ventricular tissue internal stresses via vasopressin rescues trabeculation, demonstrating that tissue stresses are important to trabeculae formation. Overall, we find that tissue biomechanics is important to the formation and function of embryonic heart trabeculation. KEY POINTS: Trabeculations are fascinating and important cardiac structures and their abnormalities are linked to embryonic demise. However, their function in the heart and their mechanobiological formation processes are not completely understood. Our imaging and modelling show that tissue biomechanics is the key here. We find that trabeculations enhance cardiac wall deformability, reduce fluid pressure stresses, homogenize wall stiffness, and have alignments that are optimal for providing load-bearing structural support for the heart. We further discover that high ventricular tissue internal stresses consequent to high fluid pressures are needed for trabeculation formation through a rescue experiment, demonstrating that myocardial tissue stresses are as important as fluid flow wall shear stresses for trabeculation formation., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Hemorrhage is the leading cause of trauma death, and innovation in hemostatic technology is important. The strongly hydrophobic carbon nanofiber (CNF) coating has previously been shown to have excellent hemostatic properties. However, the understanding of how CNF coating guides the coagulation cascade and the biosafety of CNF as hemostatic agents has yet to be explored. Here, our thrombin generation assay investigation showed that CNF induced fast blood coagulation via factor (F) XII activation of the intrinsic pathway. We further performed studies of a rat vein injury and demonstrated that the CNF gauze enabled a substantial reduction of blood loss compared to both the plain gauze and kaolin-imbued gauze (QuikClot). Analysis of blood samples from the model revealed no acute toxicity from the CNF gauze, with no detectable CNF deposition in any organ, suggesting that the immobilization of CNF on our gauze prevented the infiltration of CNF into the bloodstream. Direct injection of CNF into the rat vein was also investigated and found not to elicit overt acute toxicity or affect animal survival or behavior. Finally, toxicity assays with primary keratinocytes revealed minimal toxicity responses to CNF. Our studies thus supported the safety and efficacy of the CNF hemostatic gauze, highlighting its potential as a promising approach in the field of hemostatic control.

A well-developed heart is essential for embryonic survival. There are constant interactions between cardiac tissue motion and blood flow, which determine the heart shape itself. Hemodynamic forces are a powerful stimulus for cardiac growth and differentiation. Therefore, it is particularly interesting to investigate how the blood flows through the heart and how hemodynamics is linked to a particular species and its development, including human. The appropriate patterns and magnitude of hemodynamic stresses are necessary for the proper formation of cardiac structures, and hemodynamic perturbations have been found to cause malformations via identifiable mechanobiological molecular pathways. There are significant differences in cardiac hemodynamics among vertebrate species, which go hand in hand with the presence of specific anatomical structures. However, strong similarities during development suggest a common pattern for cardiac hemodynamics in human adults. In the human fetal heart, hemodynamic abnormalities during gestation are known to progress to congenital heart malformations by birth. In this chapter, we discuss the current state of the knowledge of the prenatal cardiac hemodynamics, as discovered through small and large animal models, as well as from clinical investigations, with parallels gathered from the poikilotherm vertebrates that emulate some hemodynamically significant human congenital heart diseases., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Primary intrapulmonary thymoma (PIT) represents a rare subset of ectopic thymoma that arises solely from inside the pulmonary parenchyma. Multifocal PIT, where multiple isolated PIT origins coexist in the lungs, has only been confirmed in one previous case report, in which the patient died before surgical resection. These tumours are difficult to diagnose as imaging findings are non-specific, and non-invasive biopsy often yields inaccurate results. We present the case of a man in his 70s who was referred to thoracic surgery for resection of a presumptive endobronchial pulmonary carcinoid tumour. Only after surgical resection did we identify that the patient had multifocal PIT. In this report, we describe our diagnostic and management process for this patient and review the current literature on PIT., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Staphylococcus aureus is a highly adaptable opportunistic pathogen that can form biofilms and generate persister cells, leading to life-threatening infections that are difficult to treat with antibiotics alone. Therefore, there is a need for an effective S. aureus biofilm inhibitor to combat this public health threat. In this study, a small library of indolenine-substituted pyrazoles and pyrimido[1,2-b]indazole derivatives were synthesised, of which the hit compound exhibited promising antibiofilm activities against methicillin-susceptible S. aureus (MSSA ATCC 29213) and methicillin-resistant S. aureus (MRSA ATCC 33591) at concentrations significantly lower than the planktonic growth inhibition. The hit compound could prevent biofilm formation and eradicate mature biofilms of MSSA and MRSA, with a minimum biofilm inhibitory concentration (MBIC 50 ) value as low as 1.56 µg/mL and a minimum biofilm eradication concentration (MBEC 50 ) value as low as 6.25 µg/mL. The minimum inhibitory concentration (MIC) values of the hit compound against MSSA and MRSA were 50 µg/mL and 25 µg/mL, respectively, while the minimum bactericidal concentration (MBC) values against MSSA and MRSA were > 100 µg/mL. Preliminary structure-activity relationship analysis reveals that the fused benzene ring and COOH group of the hit compound are crucial for the antibiofilm activity. Additionally, the compound was not cytotoxic to human alveolar A549 cells, thus highlighting its potential as a suitable candidate for further development as a S. aureus biofilm inhibitor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Left ventricle myocardium has a complex micro-architecture, which was revealed to consist of myocyte bundles arranged in a series of laminar sheetlets. Recent imaging studies demonstrated that these sheetlets re-orientated and likely slided over each other during the deformations between systole and diastole, and that sheetlet dynamics were altered during cardiomyopathy. However, the biomechanical effect of sheetlet sliding is not well-understood, which is the focus here. We conducted finite element simulations of the left ventricle (LV) coupled with a windkessel lumped parameter model to study sheetlet sliding, based on cardiac MRI of a healthy human subject, and modifications to account for hypertrophic and dilated geometric changes during cardiomyopathy remodeling. We modeled sheetlet sliding as a reduced shear stiffness in the sheet-normal direction and observed that (1) the diastolic sheetlet orientations must depart from alignment with the LV wall plane in order for sheetlet sliding to have an effect on cardiac function, that (2) sheetlet sliding modestly aided cardiac function of the healthy and dilated hearts, in terms of ejection fraction, stroke volume, and systolic pressure generation, but its effects were amplified during hypertrophic cardiomyopathy and diminished during dilated cardiomyopathy due to both sheetlet angle configuration and geometry, and that (3) where sheetlet sliding aided cardiac function, it increased tissue stresses, particularly in the myofibre direction. We speculate that sheetlet sliding is a tissue architectural adaptation to allow easier deformations of the LV walls so that LV wall stiffness will not hinder function, and to provide a balance between function and tissue stresses. A limitation here is that sheetlet sliding is modeled as a simple reduction in shear stiffness, without consideration of micro-scale sheetlet mechanics and dynamics., (© 2023. The Author(s).)

Increased cardiac stiffness hinders proper left ventricular (LV) expansion, resulting in decreased volume and diastolic dysfunction. LV expanders are spring-like devices designed to improve diastolic function by facilitating mechanical outward expansion. Implantations in animals and humans have shown promising results, yet further evaluation is needed to assess a range of functions and the risk of use. In this computational study, the effectiveness and potential use of a generic LV expander were assessed by using previously generated finite-element models of induced heart failure with preserved ejection fraction (HFpEF). Following implantation, the treated models were compared to the corresponding untreated and healthy pre-induction models. The influence of device orientation and its material properties was also examined. Our results demonstrated a reduction in LV pressure and a volumetric improvement. Computed LV stresses have shown no gross irregularities. The device contributed to stress elevation during diastole while having a minor effect during systole, supporting a basic safety profile. This is the first study to use numerical analysis to assess LV expanders' performance on different HFpEF phenotypes. Improvement in heart function was demonstrated in both subjects, suggesting its potential use in various HFpEF manifestations, yet customization and optimal deployment are essential to improve heart performance., Competing Interests: The authors have no conflict of interest to declare., (© 2023 The Authors.)

Fetuses with critical aortic stenosis (FAS) are at high risk of progression to HLHS by the time of birth (and are thus termed "evolving HLHS"). An in-utero catheter-based intervention, fetal aortic valvuloplasty (FAV), has shown promise as an intervention strategy to circumvent the progression, but its impact on the heart's biomechanics is not well understood. We performed patient-specific computational fluid dynamic (CFD) simulations based on 4D fetal echocardiography to assess the changes in the fluid mechanical environment in the FAS left ventricle (LV) directly before and 2 days after FAV. Echocardiograms of five FAS cases with technically successful FAV were retrospectively analysed. FAS compromised LV stroke volume and ejection fraction, but FAV rescued it significantly. Calculations to match simulations to clinical measurements showed that FAV approximately doubled aortic valve orifice area, but it remained much smaller than in healthy hearts. Diseased LVs had mildly stenotic mitral valves, which generated fast and narrow diastolic mitral inflow jet and vortex rings that remained unresolved directly after FAV. FAV further caused aortic valve damage and high-velocity regurgitation. The high-velocity aortic regurgitation jet and vortex ring caused a chaotic flow field upon impinging the apex, which drastically exacerbated the already high energy losses and poor flow energy efficiency of FAS LVs. Two days after the procedure, FAV did not alter wall shear stress (WSS) spatial patterns of diseased LV but elevated WSS magnitudes, and the poor blood turnover in pre-FAV LVs did not significantly improve directly after FAV. FAV improved FAS LV's flow function, but it also led to highly chaotic flow patterns and excessively high energy losses due to the introduction of aortic regurgitation directly after the intervention. Further studies analysing the effects several weeks after FAV are needed to understand the effects of such biomechanics on morphological development., (© 2023. The Author(s).)

Left atrial ligation (LAL) of the chick embryonic heart is a model of the hypoplastic left heart syndrome (HLHS) where a purely mechanical intervention without genetic or pharmacological manipulation is employed to initiate cardiac malformation. It is thus a key model for understanding the biomechanical origins of HLHS. However, its myocardial mechanics and subsequent gene expressions are not well-understood. We performed finite element (FE) modeling and single-cell RNA sequencing to address this. 4D high-frequency ultrasound imaging of chick embryonic hearts at HH25 (ED 4.5) were obtained for both LAL and control. Motion tracking was performed to quantify strains. Image-based FE modeling was conducted, using the direction of the smallest strain eigenvector as the orientations of contractions, the Guccione active tension model and a Fung-type transversely isotropic passive stiffness model that was determined via micro-pipette aspiration. Single-cell RNA sequencing of left ventricle (LV) heart tissues was performed for normal and LAL embryos at HH30 (ED 6.5) and differentially expressed genes (DEG) were identified.After LAL, LV thickness increased by 33%, strains in the myofiber direction increased by 42%, while stresses in the myofiber direction decreased by 50%. These were likely related to the reduction in ventricular preload and underloading of the LV due to LAL. RNA-seq data revealed potentially related DEG in myocytes, including mechano-sensing genes (Cadherins, NOTCH1, etc.), myosin contractility genes (MLCK, MLCP, etc.), calcium signaling genes (PI3K, PMCA, etc.), and genes related to fibrosis and fibroelastosis (TGF-β, BMP, etc.). We elucidated the changes to the myocardial biomechanics brought by LAL and the corresponding changes to myocyte gene expressions. These data may be useful in identifying the mechanobiological pathways of HLHS., (© 2023. The Author(s).)

Background: Echocardiographic quantification of fetal cardiac strain is important to evaluate function and the need for intervention, with both two-dimensional (2D) and three-dimensional (3D) strain measurements currently feasible. However, discrepancies between 2D and 3D measurements have been reported, the etiologies of which are unclear. This study sought to determine the etiologies of the differences between 2D and 3D strain measurements., Methods: A validated cardiac motion-tracking algorithm was used on 3D cine ultrasound images acquired in 26 healthy fetuses. Both 2D and 3D myocardial strain quantifications were performed on each image set for controlled comparisons. Finite element modeling of 2 left ventricle (LV) models with minor geometrical differences were performed with various helix angle configurations for validating image processing results., Results: Three-dimensional longitudinal strain (LS) was significantly lower than 2D LS for the LV free wall and septum but not for the right ventricular (RV) free wall, while 3D circumferential strain (CS) was significantly higher than 2D CS for the LV, RV, and septum. The LS discrepancy was due to 2D long-axis imaging not capturing the out-of-plane motions associated with LV twist, while the CS discrepancy was due to the systolic motion of the heart toward the apex that caused out-of-plane motions in 2D short-axis imaging. A timing mismatch between the occurrences of peak longitudinal and circumferential dimensions caused a deviation in zero-strain referencing between 2D and 3D strain measurements, contributing to further discrepancies between the 2., Conclusions: Mechanisms for discrepancies between 2D and 3D strain measurements in fetal echocardiography were identified, and inaccuracies associated with 2D strains were highlighted. Understanding of this mechanism is useful and important for future standardization of fetal cardiac strain measurements, which we propose to be important in view of large discrepancies in measured values in the literature., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

The helix angle configuration of the myocardium is understood to contribute to the heart function, as finite element (FE) modeling of postnatal hearts showed that altered configurations affected cardiac function and biomechanics. However, similar investigations have not been done on the fetal heart. To address this, we performed image-based FE simulations of fetal left ventricles (LV) over a range of helix angle configurations, assuming a linear variation of helix angles from epicardium to endocardium. Results showed that helix angles have substantial influence on peak myofiber stress, cardiac stroke work, myocardial deformational burden, and spatial variability of myocardial strain. A good match between LV myocardial strains from FE simulations to those measured from 4D fetal echo images could only be obtained if the transmural variation of helix angle was generally between 110 and 130°, suggesting that this was the physiological range. Experimentally discovered helix angle configurations from the literature were found to produce high peak myofiber stress, high cardiac stroke work, and a low myocardial deformational burden, but did not coincide with configurations that would optimize these characteristics. This may suggest that the fetal development of myocyte orientations depends concurrently on several factors rather than a single factor. We further found that the shape, rather than the size of the LV, determined the manner at which helix angles influenced these characteristics, as this influence changed significantly when the LV shape was varied, but not when a heart was scaled from fetal to adult size while retaining the same shape. This may suggest that biomechanical optimality would be affected during diseases that altered the geometric shape of the LV., (© 2022. The Author(s).)

The Computer-aided Diagnosis or Detection (CAD) approach for skin lesion analysis is an emerging field of research that has the potential to alleviate the burden and cost of skin cancer screening. Researchers have recently indicated increasing interest in developing such CAD systems, with the intention of providing a user-friendly tool to dermatologists to reduce the challenges encountered or associated with manual inspection. This article aims to provide a comprehensive literature survey and review of a total of 594 publications (356 for skin lesion segmentation and 238 for skin lesion classification) published between 2011 and 2022. These articles are analyzed and summarized in a number of different ways to contribute vital information regarding the methods for the development of CAD systems. These ways include: relevant and essential definitions and theories, input data (dataset utilization, preprocessing, augmentations, and fixing imbalance problems), method configuration (techniques, architectures, module frameworks, and losses), training tactics (hyperparameter settings), and evaluation criteria. We intend to investigate a variety of performance-enhancing approaches, including ensemble and post-processing. We also discuss these dimensions to reveal their current trends based on utilization frequencies. In addition, we highlight the primary difficulties associated with evaluating skin lesion segmentation and classification systems using minimal datasets, as well as the potential solutions to these difficulties. Findings, recommendations, and trends are disclosed to inform future research on developing an automated and robust CAD system for skin lesion analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Staphylococcal-associated surgical site infections (SSI) are common nosocomial infections in healthcare facilities worldwide. The use of antiseptic-coated sutures has been recommended to minimise the risk of SSI in clinical settings. However, as there has been a growing concern over antibiotic resistance resulting from antiseptic usage, development of antimicrobial sutures using alternative compounds is necessary. In this study, menadione (2-methyl-1,4-napthoquinone), also known as Vitamin K 3, was evaluated as a potential antimicrobial compound for suture coating. The anti-staphylococcal activity of menadione was assessed using microbroth dilution method and biofilm inhibition assays. The low menadione minimum biofilm inhibitory concentration values against both methicillin-susceptible and -resistant S. aureus strains indicate its inhibitory activity against staphylococcal biofilm. Menadione-coated sutures were prepared by dip-coating surgical sutures in slurries containing poly(D,L-lactide-co-glycolide) polymers (either 65:35 or 75:25) and calcium stearate. Zone of inhibition assays showed dose-dependent antimicrobial effects of the sutures up to four days. A ∼3 log10 colony forming unit/ml reduction of adherent bacteria (p < 0.05) on the sutures was demonstrated via bacterial adherence assays. The integrity and tensile strength of the sutures were unaffected by the coating procedure. In view of the increased antibiotic resistance and limited antimicrobials, menadione may be potentially useful for antimicrobial coating of surgical sutures., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tay Sun Tee reports financial support was provided by 10.13039/501100004386University of Malaya., (© 2023 The Authors.)

Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for about half of heart failure cases, but the progression of cardiac biomechanics during pathogenesis is not completely understood. We investigated a published porcine model of HFpEF, generated by progressive constriction of an aortic cuff causing progressive left ventricle (LV) pressure overload, and characterized by hypertrophy, diastolic dysfunction and overt HF with elevated plasma beta natriuretic peptide (BNP). We characterized morphological and functional features and performed image-based finite element modelling over multiple time points, so as to understand how biomechanics evolved with morphological and functional changes during pathogenesis, and to provide data for future growth and remodeling investigations. Results showed that the hypertrophic responses quickly manifested and were effective at preventing an elevation of systolic myocardial stresses, suggesting active compensated remodeling. Consequent to the hypertrophy, diastolic myocardial stresses decreased despite the elevations in diastolic pressures. The left ventricle hypertrophy (LVH) myocardium also exhibited a quick elevation of active tension at the onset of the disease. There was a progressive and significant decrease in myocardial strain, which was more significant in the longitudinal direction. Further, elevated myocardial stiffness and diastolic pressures, which reflected diastolic dysfunction, also manifested, but this was delayed from the onset of the disease. Correlation analysis showed that hypertrophy was closely correlated to systolic pressure, active tension and systolic myocardial stress, suggesting that these factors may play a role in initiating hypertrophy. Myocardial stiffness was weakly correlated to LV pressures and myocardial stresses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A substantial proportion of heart failure patients have a preserved left ventricular (LV) ejection fraction (HFpEF). This condition carries a high burden of morbidity and mortality and has limited therapeutic options. left ventricular pressure overload leads to an increase in myocardial collagen content, causing left ventricular stiffening that contributes to the development of heart failure patients have a preserved left ventricular ejection fraction. Although several heart failure patients have a preserved left ventricular ejection fraction models have been developed in recent years to aid the investigation of mechanical alterations, none has investigated different phenotypes of the disease and evaluated the alterations in material properties. In this study, two similar healthy swine were subjected to progressive and prolonged pressure overload to induce diastolic heart failure characteristics, providing a preclinical model of heart failure patients have a preserved left ventricular ejection fraction. Cardiac magnetic resonance imaging (cMRI) scans and intracardiac pressures were recorded before and after induction. In both healthy and disease states, a corresponding finite element (FE) cardiac model was developed via mesh morphing of the Living Heart Porcine model. The material properties were derived by calibrating to its passive and active behavior. The change in the passive behavior was predominantly isotropic when comparing the geometries before and after induction. Myocardial thickening allowed for a steady transition in the passive properties while maintaining tissue incompressibility. This study highlights the importance of hypertrophy as an initial compensatory response and might also pave the way for assessing disease severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Weissmann, Charles, Richards, Yap and Marom.)

The evaluation of fetal heart mechanical function is becoming increasingly important for determining the prognosis and making subsequent decisions on the treatment and management of congenital heart diseases. Finite Element (FE) modelling can potentially provide detailed information on fetal hearts, and help perform virtual interventions to assist in predicting outcomes and supporting clinical decisions. Previous FE studies have enabled an improved understanding of healthy and diseased fetal heart biomechanics. However, to date, the mechanical properties of the fetal myocardium have not been well characterized which limits the reliability of such modelling. Here, we characterize the passive mechanical properties of late fetal and neonatal porcine hearts via biaxial mechanical testing as a surrogate for human fetal heart mechanical properties. We used samples from both the right and left ventricles over the late gestational period from 85 days of gestation to birth. Constitutive modelling was subsequently performed with a transversely isotropic Fung-type model and a Humphrey-type model, using fiber orientations identified with histology. We found no significant difference in mechanical stiffness across all age groups and between the right and left ventricular samples. This was likely due to the similarity in LV and RV pressures in the fetal heart, and similar gestational maturity across these late gestational ages. We thus recommend using the constitutive model for the average stress-stress behaviour of the tissues in future modelling work. Furthermore, we characterized the variability of the stiffness to inform such work., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In cases of fetal aortic stenosis and evolving Hypoplastic Left Heart Syndrome (feHLHS), aortic stenosis is associated with specific abnormalities such as retrograde or bidirectional systolic transverse arch flow. Many cases progressed to hypoplastic left heart syndrome (HLHS) malformation at birth, but fetal aortic valvuloplasty can prevent the progression in many cases. Since both disease and intervention involve drastic changes to the biomechanical environment, in-vivo biomechanics likely play a role in inducing and preventing disease progression. However, the fluid mechanics of feHLHS is not well-characterized. Here, we conduct patient-specific echocardiography-based flow simulations of normal and feHLHS left ventricles (LV), to understand the essential fluid dynamics distinction between the two cohorts. We found high variability across feHLHS cases, but also the following unifying features. Firstly, feHLHS diastole mitral inflow was in the form of a narrowed and fast jet that impinged onto the apical region, rather than a wide and gentle inflow in normal LVs. This was likely due to a malformed mitral valve with impaired opening dynamics. This altered inflow caused elevated vorticity dynamics and wall shear stresses (WSS) and reduced oscillatory shear index at the apical zone rather than mid-ventricle. Secondly, feHLHS LV also featured elevated systolic and diastolic energy losses, intraventricular pressure gradients, and vortex formation numbers, suggesting energy inefficiency of flow and additional burden on the LV. Thirdly, feHLHS LV had poor blood turnover, suggesting a hypoxic environment, which could be associated with endocardial fibroelastosis that is often observed in these patients., (© 2022. The Author(s).)