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Establishment of subcutaneous transplantation platform for delivering induced pluripotent stem cell-derived insulin-producing cells

Potential trend of regenerative treatment for type I diabetes has been introduced for more than a decade. However, the technologies regarding insulin-producing cell (IPC) production and transplantation are still being developed. Here, we propose the potential IPC production protocol employing mouse gingival fibroblast-derived induced pluripotent stem cells (mGF-iPSCs) as a resource and the pre-clinical approved subcutaneous IPC transplantation platform for further clinical confirmation study. With a multi-step induction protocol, the functional and matured IPCs were generated by 13 days with a long-term survival capability. Further double encapsulation of mGF-iPSC-derived IPCs (mGF-iPSC-IPCs) could preserve the insulin secretion capacity and the transplantation potential of the generated IPCs. To address the potential on IPC transplantation, a 2-step subcutaneous transplantation procedure was established, comprising 1) vascularized subcutaneous pocket formation and 2) encapsulated IPC bead transplantation. The in vivo testing confirmed the safety and efficiency of the platform along with less inflammatory response which may help minimize tissue reaction and graft rejection. Further preliminary in vivo testing on subcutaneous IPC-bead transplantation in an induced type I diabetic mouse model showed beneficial trends on blood glucose control and survival rate sustainability of diabetic mice. Taken together, an established mGF-iPSC-IPC generation protocol in this study will be the potential backbone for developing the iPSC-derived IPC production employing human and animal cell resources. As well as the potential further development of IPC transplantation platform for diabetes treatment in human and veterinary practices using an established subcutaneous encapsulated IPC-bead transplantation platform presented in this study.

The impact of air pollution on career changes among Chinese workers

A feature-based approach for atlas selection in automatic pelvic segmentation

Accurate and efficient automatic segmentation is essential for various clinical tasks such as radiotherapy treatment planning. However, atlas-based segmentation still faces challenges due to the lack of representative atlas dataset and the computational limitations of deformation algorithms. In this work, we have proposed an atlas selection procedure (subset atlas grouping approach, MAS-SAGA) which utilized both image similarity and volume features for selecting the best-fitting atlases for contour propagation. A dataset of anonymized female pelvic Computed Tomography (CT) images demonstrated that MAS-SAGA significantly outperforms conventional multi-atlas-based segmentation (cMAS) in terms of Dice Similarity Coefficient (DSC) and 95th Percentile Hausdorff Distance (95HD) for bladder and rectum segmentation using a three-fold cross-validation strategy. The proposed procedure also reduced computation time compared to cMAS, making it a promising tool for medical image analysis applications. In addition, we have evaluated two distinct atlas selection methods: the Feature-based Atlas Selection Approach (MAS-FASA) and the Similarity-based Atlas Selection Approach (MAS-SIM). We investigate the differences between these two methods in terms of their ability to select the best fitting atlases. The findings demonstrated that MAS-FASA selected different atlases than MAS-SIM, resulting in improved segmentation performance overall. It highlighted the potential of feature-based subgrouping techniques in enhancing the efficacy of MAS algorithms in the field of medical image segmentation.

Cost-efficient behavioral modeling of antennas by means of global sensitivity analysis and dimensionality reduction

Abstract Computational tools, particularly electromagnetic (EM) solvers, are now commonplace in antenna design. While ensuring reliability, EM simulations are time-consuming, leading to high costs associated with EM-driven procedures like parametric optimization or statistical design. Various techniques have been developed to address this issue, with surrogate modeling methods garnering particular attention due to their potential advantages. One key benefit is the promise of unprecedented acceleration in handling design problems that require repetitive system evaluations. However, behavioral modeling of antennas is an intrinsic endeavor. Challenges include the curse of dimensionality and the high nonlinearity of antenna characteristics. Moreover, design utility necessitates that the models are defined across wide ranges of frequency, geometry dimensions, and material parameters, posing a significant bottleneck for existing modeling frameworks. This paper introduces an innovative approach to constructing design-ready behavioral surrogates for antenna structures. Our methodology involves a rapid global sensitivity analysis (GSA) algorithm developed to determine a set of parameter space directions that maximize antenna response variability. The latter are obtained from spectral analysis of the GSA-based sensitivity indicators, and employed to define a reduced-dimensionality domain of the metamodel. The dependability of the model constructed in such a domain is superior over conventional surrogates while being suitable for design purposes. These benefits have been conclusively showcased using several microstrip antennas and illustrated by a number of design scenarios involving antenna geometry optimization for a variety of performance specifications.

Diabetes knowledge and glycemic control among type 2 diabetes patients at public hospitals in Debre Berhan, Ethiopia

Background Diabetes mellitus is a growing global health issue, especially in low- and middle-income countries like Ethiopia. To the best of our knowledge, the impact of diabetes knowledge on glycemic control in Ethiopia has not been documented. This study assessed diabetes knowledge and its relationship with glycemic control among Type 2 diabetes (T2DM) patients in Debre Berhan, Ethiopia. Methods A cross-sectional study was conducted involving 380 patients diagnosed with T2DM who were receiving care at two hospitals in Debre Berhan from January 1 to March 30, 2024. Patients’ knowledge was assessed using the modified Diabetes Knowledge Questionnaire (DKQ-18), categorizing outcomes as either good or poor. Glycemic control was evaluated using hemoglobin A1c (HbA1c) levels. Logistic regression analyses were conducted to identify predictors of poor diabetes knowledge. Correlation analysis was used to evaluate the relationship between knowledge and glycemic control. Results Among the 380 participants, 75.2% were older than 45 years, and 51.3% were male. Overall, 62.4% of participants had poor knowledge of diabetes. Additionally, 72.6% had poor glycemic control, with HbA1C levels ≥7%. The mean average diabetes knowledge score was 7.9 (SD = 3.49) out of 18, and the median HbA1C was 8%. Diabetes knowledge was significantly associated (p < 0.05) with patients’ educational level, occupation, family history of diabetes, and glycemic control. The Spearman correlation coefficient between HbA1C and diabetes knowledge scores was -0.166 (p = 0.001), suggesting a weak but statistically significant inverse relationship between knowledge scores and HbA1C levels. Conclusions The study found that the majority of patients had a low level of diabetes knowledge. Enhancing diabetes education and identifying additional factors that influence glycemic control are crucial for achieving optimal diabetes management in Ethiopia. Public health initiatives should prioritize enhancing diabetes knowledge through targeted educational programs and resources to support effective diabetes management and achieve optimal glycemic control.

Subclinical patterns of cardiac involvement by transthoracic echocardiography in individuals with mild initial COVID-19

Abstract The aim of this study was to evaluate the subclinical patterns and evolution of cardiac abnormalities via transthoracic echocardiography (TTE) in patients with mild initial COVID-19 illness. A total of 343 infected individuals (163 males; age 44 (interquartile range, IQR 35–52) years) years) underwent serial TTE assessments at a median of 109 (interquartile range (IQR), 77–177) and 327 (276–379) days after infection. Compared with those of non-COVID-19-infected controls (n = 94, male n = 49), baseline systolic (LVEF, TAPSE) and diastolic function (eʹ, aʹ, E/eʹ) were significantly different in infected participants (p < 0.05 for all). Compared with baseline assessments, there was a reduction in global longitudinal strain (GLS) and an increase in the E wave, E/A ratio and E/eʹ at follow-up. At baseline, symptomatic participants had a lower LVEF and TAPSE and increased IVRT, eʹ and E/eʹ. At follow-up, symptomatic patients had a lower LV end-diastolic diameter (LVEDd). Symptoms were independently associated with E/eʹ at baseline (OR (95% CI) 1.45 (1.12–1.87), p = 0.005). Symptoms at follow-up were associated with LVEDd, measured either at baseline (OR: 0.91 (0.86, 0.96), p < 0.001) or follow-up (OR (95% CI) 0.91 (0.86–0.96), p < 0.001). There were significant associations for GLS and troponin and E/eʹ with CRP and NTproBNP at baseline. In the present cohort of COVID-19-infected individuals with mild initial illness, echocardiographic measurements revealed significant yet subclinical differences in systolic and diastolic function compared with controls, as well as between individuals with cardiac symptoms and those without. All the measured differences were small in magnitude and thus unlikely to be detectable clinically at the individual level.

Introduced substrates trigger colonization by reef-associated fish in a degraded coastal system

Coastal reefs benefit the survival and growth of mobile organisms by providing shelter and increased food availability. Under increasing pressure from human activities, the coverage of subtidal reefs has decreased along the world’s coasts. This decline is motivating efforts to restore these important habitats by re-introducing hard substrates into the coastal zone. However, many such projects use artificial substrates, such as concrete or metal, that are not naturally occurring in the marine environment. We experimentally introduced hard substrates that were either historically common in a soft sediment-dominated ecosystem, or are mimicking these substrates with biodegradable material, and monitored the substrates for mobile species use (fish and invertebrates). Six substrates were tested: cockle shells, rocks of two sizes (cobbles and pebbles), wood, artificial reefs of calcium carbonate with shell fragments, and biodegradable structures based on potato starch. Within one year, fish and prawns were already attracted to all of the introduced substrates. On average, fish were nearly five times as abundant and prawn abundance increased nearly 30-fold on the artificial reefs, compared to the bare sand bottom control. The community composition on the reefs differed significantly from the sand bottom community, but there were no differences between the types of introduced substrates. Interestingly, the substrates attracted reef-associated fish, but also soft-sediment dependent species, such as different species of flatfish and gobies. Our results show that, even over shorter timespans, introductions of hard substrates provide opportunities to support associated mobile communities in degraded soft-sediment systems.

Superconducting quantum computing optimization based on multi-objective deep reinforcement learning

Effects of gastrointestinal parasites on fecal glucocorticoids and behaviour in vervet monkeys (Chlorocebus pygerythrus)

Relationships between parasites, host physiology, and behaviours are complex. Parasites can influence host hormonal microenvironment and behaviour through “sickness behaviours” that generally conserve energy. Using a parasite removal experiment, we examined the effects of gastrointestinal parasites on fecal glucocorticoid metabolites (fGC) and behaviours of vervet monkeys (Chlorocebus pygerythrus) at Lake Nabugabo, Uganda. We collected parasitological, hormonal, and behavioural data from adult and subadult male and female vervets (N = 19) in 2014 across four study phases: pre-deworming, post-deworming, early reinfection, and late reinfection as well as in 2015. Overall, there was no decrease in fGC after deworming, but there was an increase following natural reinfection. There was no change in feeding across study phases; however, moving, grooming, and resting changed between the post-deworming and late reinfection phases, but not always in the predicted direction. Comparing behaviour across the same months in the following year as in the 2014 experimental study period, we found no differences in moving, feeding, grooming, and resting events. Despite behavioural variation between study phases, we cannot conclude that behavioural changes are due to parasitism rather than other seasonal variation. However, fGC increased following reinfection, which is consistent with parasitism being costly for hosts.

Tofacitinib and budesonide treatment affect stemness and chemokine release in IBD patient-derived colonoids

Abstract Restoration of the intestinal epithelial barrier is crucial for achieving mucosal healing, the therapeutic goal for inflammatory bowel disease (IBD). During homeostasis, epithelial renewal is maintained by crypt stem cells and progenitors that cease to divide as they differentiate into mature colonocytes. Inflammation is a major effector of mucosal damage in IBD and has been found to affect epithelial stemness, regeneration and cellular functions. However, the impact of immune cell-modulating IBD drugs on epithelial homeostasis and repair is poorly understood. It is likely that these drugs will have distinct mechanisms of action (MOA) in intestinal epithelium relevant for homeostasis that will vary among patients. We investigated cellular effects of pan-Janus Kinase (JAK) inhibitor tofacitinib and the corticosteroid budesonide on uninflamed and TNF + Poly(I:C) stimulated human colon organoids (colonoids) from healthy donors and IBD-patients. Our findings reveal that although both tofacitinib and budesonide exhibit anti-inflammatory effects, tofacitinib increased colonoid size and proliferation during differentiation, and promoted epithelial stemness. In contrast, budesonide decreased colonoid size and showed no consistent effect on proliferation or stemness. Our study demonstrates the value of employing human colonoids to investigate how IBD drugs affect intestinal epithelial cells and inter-individual variations relevant to mucosal healing and personalized IBD treatment.

Incorporating preference uncertainty in best worst scaling

In this paper, we enhance the Best-Worst Scaling (BWS) method by incorporating participants’ preference uncertainty into the conventional BWS, known as case 1. In this context, respondents are tasked with making trade-offs among a set of items of interest. Applying this novel extended BWS method to a sample of Argentinian wine consumers (n = 342), we aim to a) provide a more informative elicitation of consumers’ relative preferences for 16 wine attributes; b) identify the level of uncertainty with each of the attributes, exploring differences between the most and least important wine attributes influencing purchasing wine; and c) compare the results of the extended BWS with the standard BWS. Our findings indicate variability in uncertainty levels on the importance of wine attributes when purchasing wine within and across attributes. Moreover, accounting for participants’ preference uncertainty can alter the ranking of preferences obtained through the standard approach. This alteration is due to both accounting for preference uncertainty itself as well as the uncertainty indicator used. Although this approach is a way to mitigate biases associated with respondents’ preference certainty, it is recommended that preference uncertainty heterogeneity is investigated using different indicators.

Change point detection in brucellosis time series from 2010 to 2023 in Xinjiang China using the BEAST algorithm

Influence of Messa di Voce speed on vocal stability of untrained, healthy subjects

Introduction Despite its importance in voice training, comprehensive research into sustained vowel phonation with constant pitch and increasing and decreasing loudness, the so-called Messa di Voce, is lacking. The study examines the laryngeal behavior during Messa di Voce, regarding the impact of the speed of execution on voice stability parameters. Materials and methods Nine untrained, healthy subjects (5 female, 4 male) were asked to perform Messa di Voce exercises on the vowel [i:], involving a gradual increase and decrease of volume. During the first task, each phase should take 3 s, whereas in the second task, each phase should take 1 s. Female subjects sang pitch B3 (fundamental frequency fo ≈ 247 Hz), and male subjects pitch B2 (fo ≈ 124 Hz). Throughout phonation, synchronous recordings were captured through high-speed videolaryngoscopy (HSV), electroglottography, and audio signals. Subsequently, the Glottal Area Waveform was extracted from the HSV data. The tasks’ duration and calculated parameters (including, e.g., Open Quotient (OQ), Closing Quotient (ClQ), Relative Average Perturbation (RAP)), excluding parts of the signal with stationary sound pressure level (SPL), were analyzed with correlation analysis and statistical analysis (Analysis of Variance and subsequent multiple comparisons). Results Subjects shortened the requested task length by factor ≈ 0.5. The fo remained almost stable for most subjects and tasks. There were strong negative correlations between SPL and both OQ and ClQ. The median RAP appears to decrease towards the SPL apex and then increase again. Statistical effects were shown especially for females during the fast task, which may be due to raised SPL. Conclusion There was no specific effect on stability found corresponding to the task’s speed. Also, no major vocal instabilities at a specific sound pressure level were apparent, indicating no transitions as they exist for fo regions with registration events.

Improved constructs for bait RNA display in a bacterial three-hybrid assay

Research on technological innovation decision-making considering government subsidies and corporate reputation

Aiming at the information asymmetry between pharmaceutical enterprises’ technological innovation decisions and government subsidy strategy, this paper establishes a differential game model consisting of the government and a single pharmaceutical company, proposes three different government subsidy strategies, and obtains an equilibrium solution with the help of the Hamilton-Jacobi-Bellman equation, taking into consideration of the transmission effect of the enterprise’s reputation. First, the innovation decisions of pharmaceutical firms without government subsidies are analysed, and based on this, the optimal strategies with government subsidies for non-cooperative pacts and cooperation between the government and enterprises are analysed separately. In addition, the effects of different subsidy strategies on the government’s investment efficiency, corporate reputation, and the choice of corporate innovation strategies are compared, and the results are verified by numerical analysis. Finally, based on the results of the study, references and suggestions are provided for the formulation of government subsidy policies as well as corporate innovation decisions. The results show that: government subsidies can effectively stimulate the innovation ability of pharmaceutical enterprises and improve their reputation; the more sensitive an enterprise’s reputation is to the coefficient of technological innovation, the more it can improve the enterprise’s innovation level; and the coordination contract of government-enterprise cooperation can realize the Pareto improvement of the benefits of the government and enterprises.

Author Correction: Genome resequencing and genome-wide polymorphisms in mosquito vectors Aedes aegypti and Aedes albopictus from south India

Multi-session tDCS over the posterior parietal cortex and associative memory

Associative memory (AM) plays a crucial role in our ability to link disparate elements of our experiences, yet it is especially vulnerable to age-related decline and pathological conditions. Non-invasive brain stimulation (NIBS), particularly transcranial direct current stimulation (tDCS), has been investigated as a potential intervention to enhance cognitive functions, including AM. Previous tDCS studies yielded inconsistent results, often due to variations in stimulation sites and protocols. Nonetheless, enough evidence suggests that tDCS over the posterior parietal cortex (PPC) can improve AM performance. This study aimed to investigate the cumulative effects of multiple anodal tDCS over the PPC on AM performance alongside item memory and verbal fluency. In a randomized sham-controlled trial, 59 healthy young adults were assigned to either anodal or sham stimulation group, receiving tDCS (1.5 mA, for 20 minutes, at P3) over three consecutive days. Memory performance was assessed at four timepoints: pretest, immediately after the first session, posttest (Day 5), and follow-up (Day 9). Although tDCS was well tolerated, the anticipated enhancement of memory performance was not observed. We interpret these findings in the light of methodological considerations and propose potential explanations for the observed results emphasizing the large between-participants variability in memory performance as a significant factor that may have hindered the detection of tDCS effects.

An analytical cross-sectional study on optimal (timely or cumulative age-appropriate) routine childhood immunization coverage in the communities of Ebonyi state, Nigeria

Author Correction: An endosomal tether undergoes an entropic collapse to bring vesicles together

Modelling epidemiological dynamics with pseudo-recovery via fractional-order derivative operator and optimal control measures

In this study, a new deterministic mathematical model based on fractional-order derivative operator that describes the pseudo-recovery dynamics of an epidemiological process is developed. Fractional-order derivative of Caputo type is used to examine the effect of memory in the spread process of infectious diseases with pseudo-recovery. The well-posedness of the model is qualitatively investigated through Banach fixed point theory technique. The spread of the disease in the population is measured by analysing the basic reproduction of the model with respect to its parameters through the sensitivity analysis. Consequently, the analysis is extended to the fractional optimal control model where time-dependent preventive strategy and treatment measure are characterized by Pontryagin’s maximum principle. The resulting Caputo fractional-order optimality system is simulated to understand how both preventive and treatment controls affect the pseudo-recovery dynamics of infectious diseases in the presence of memory. Graphical illustrations are shown to corroborate the qualitative results, and to demonstrate the importance of memory effects in infectious disease modelling. It is shown that time-dependent preventive strategy and treatment measure in the presence of memory engenders significant reduction in the spread of the disease when compared with memoryless situation.