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Abstract Vaccination has played a critical role in mitigating COVID-19. Despite the availability of licensed vaccines, there remains a pressing need for improved vaccine platforms that provide high protection, safety, and versatility, while also reducing vaccine costs. In response to these challenges, our aim is to create a self-adjuvanted vaccine against SARS-CoV-2, utilizing Virus-Like Particles (VLPs) as the foundation. To achieve this, we produced bacteriophage (Qβ) VLPs in a prokaryotic system and purified them using a rapid and cost-effective strategy involving organic solvents. This method aims to solubilize lipids and components of the cell membrane to eliminate endotoxins present in bacterial samples. For vaccine formulation, Receptor Binding Domain (RBD) antigens were conjugated using chemical crosslinkers, a process compatible with Good Manufacturing Practice (GMP) standards. Transmission Electron Microscopy (TEM) confirmed the expected folding and spatial configuration of the QβVLPs vaccine. Additionally, vaccine formulation assessment involved SDS-PAGE stained with Coomassie Brilliant Blue, Western blotting, and stereomicroscopic experiments. In vitro and in vivo evaluations of the vaccine formulation were conducted to assess its capacity to induce a protective immune response without causing side effects. Vaccine doses of 20 µg and 50 µg stimulated the production of neutralizing antibodies. In in vivo testing, the group of animals vaccinated with 50 µg of vaccine formulation provided complete protection against virus infection, maintaining stable body weight without showing signs of disease. In conclusion, the QβVLPs-RBD vaccine has proven to be effective and safe, eliminating the necessity for supplementary adjuvants and offering a financially feasible approach. Moreover, this vaccine platform demonstrates flexibility in targeting Variants of Concern (VOCs) via established conjugation protocols with VLPs.

Abstract Background While previous studies have examined various platforms that enable providers to connect, Virtual Hallway (VH) stands out with its unique features. The value add is that this online platform connects primary care providers and specialists for synchronous phone-based conversations and aims to reduce referrals and enhance the quality of referrals. VH allows providers to easily log in, select the required specialty, book call times, receive reminders, and have calls documented, ensuring a high connection rate. In May 2022, the provincial health authority in Nova Scotia, a Canadian province, and VH initiated a feasibility study facilitated through the Health Innovation Hub in Nova Scotia. The goal was to enable primary care providers to connect with specialists, thereby reducing wait times and unnecessary referrals, and facilitating timely access to relevant clinical direction for patients. The current evaluation assessed utilization, value for money in economic analysis, and consultation experiences. Methods The study used post, cross-sectional, and cost-benefit study designs. We collected data through various methods, including administratively recorded utilization, theory-driven surveys, and cost data. Utilization was measured by the number of completed consults and the number of healthcare professionals using the VH platform. We analyzed the data using a combination of descriptive statistics and a cost-benefit analysis, which also involved conducting probabilistic sensitivity analysis. Results The study found that approximately 84% of the VH consultations avoided needing in-person specialist referrals. The return on investment was 1.8 (95% CI: 0.8 to 3.0), indicating that the monetary value of the measurable benefits associated with VH exceeded the value of the resources invested. The provider experience survey revealed high satisfaction levels with VH across user groups, with 92% of specialists and 96% of primary care providers reporting being satisfied or highly satisfied with their experience. These positive indicators of provider experience were further supported by the fact that 97% of respondents agreed or strongly agreed that they intended to continue to use VH in their practice, and 97% of respondents agreed or strongly agreed that they would recommend VH to a colleague. Conclusions The study suggests that VH was well-received by users, with high levels of satisfaction reported and a reduced need for in-person referrals. It also represented value for money. Further research could explore how the availability of virtual health services can lead to reduced utilization of healthcare resources among different groups of patients.

Reiker G Ricks,1,2 Ivan A Cardenas,1,2 Jenna L Jensen,1,2 Tanner K Nelson,1,2 Randall J Olson,1 Jeff H Pettey1 1Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT, 84132, USA; 2University of Utah School of Medicine, Salt Lake City, UT, 84132, USACorrespondence: Jeff H Pettey, John A Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA, Tel +1 801-581-2352, Fax +1 801-581-3357, Email jeff.pettey@hsc.utah.eduPurpose: This study aims to investigate the differences between the heat energy produced during cataract surgery and Cumulative dissipated energy (CDE). CDE is often used as a medium for understanding the energy delivered to the eye during cataract surgery. However, the actual energy produced at the tip level of the tip is not well understood. We propose that a discrepancy may exist between the CDE reported by the surgical machine and the actual energy delivered to the eye.Methods: About 50 mL of distilled water were degassed and placed in an isobaric calorimeter. Using the Alcon Centurion and Ozil handpiece fitted with the balanced tip, an investigator immersed the phaco tip into the water and pressed the foot pedal to position 3. The device was set to 100% continuous power, vacuum to 0 mmHg, with aspiration 12 mL/min aspiration. To prevent system changes in the system within the calorimeter, the aspiration tubing was occluded. Temperature change recorded by another investigator was observed from 0 to 60 seconds. After 60 seconds the first researcher immediately released the pedal and removed the phaco tip from the water. Trials were performed 10 times using solely torsional or longitudinal settings and averaged. CDE also was recorded and averaged.Results: No significant difference was seen in the temperature change or energy calculated in Joules between ultrasound modalities, with torsional producing a magnitude of 163 J and longitudinal producing 172 J (P = 0.2). However, the CDE generated in the 60 seconds period was significantly different, with a magnitude of 61 for longitudinal compared to 24 for torsional (P < 0.001).&#x00A0Conclusion: Significantly more energy was generated using torsional ultrasound than longitudinal at the tip level of the tip. CDE did not appear to accurately reflect these differences. This suggests that other factors should be considered when evaluating CDE and surgical outcomes.Plain Language Summary: This study looked at possible differences between the energy generated during cataract surgery that is reported by the surgical device and the actual energy measured as thermal heat using different machine settings, namely longitudinal and torsional ultrasound. A common metric used for energy delivery to the eye is cumulative dissipated energy. The problem is that this measure accounts for the energy delivered to the eye where the surgical instrument passes through the cornea. Energy that is produced by the rest of the instrument that is inside the eye is less understood, although others have studied postoperative outcomes. We used a method called calorimetry to measure the thermal heat produced by the entire tip and compared this to what the machine reported as cumulative dissipated energy. Calorimetry calculates energy by measuring the change in temperature of liquids. The surgical instrument generated heat in a chamber containing water, and we used the change in temperature to calculate the energy produced by the surgical instrument. We found that longitudinal and torsional ultrasound produced similar heat energy, but the machine reported very different energy. Our results suggest that the machine may not be reporting all of the energy which the surgical instrument produces, and that surgeons may not be able to rely on cumulative dissipated energy to predict operative outcomes.Keywords: Cumulative dissipated energy, phacoemulsification, calorimetry, torsional ultrasound, longitudinal ultrasound

Chili pepper anthracnose, caused by Colletotrichum spp., is a significant biotic stress affecting chili fruits globally. While fungicide application is commonly used for disease management due to its efficiency and cost-effectiveness, excessive use poses risks to human health and the environment. Botanical fungicides offer advantages such as rapid degradation and low toxicity to mammals, making them increasingly popular for sustainable plant disease control. This study investigated the antifungal properties of Cestrum tomentosum L.f. crude extracts (CTCE) against Colletotrichum scovillei. The results demonstrated that CTCE effectively inhibited conidia germination and germ tube elongation at 40 μg/ml concentrations. Moreover, CTCE exhibited strong antifungal activity against C. scovillei mycelial growth, with an EC50 value of 18.81 μg/ml. In vivo experiments confirmed the protective and curative effects of CTCE on chili pepper fruits infected with C. scovillei. XTT analysis showed that the CTCE could significantly inhibit the cell viability of C. scovillei. Mechanistic studies revealed that CTCE disrupted the plasma membrane integrity of C. scovillei and induced the accumulation of reactive oxygen species in hyphal cells. These findings highlight CTCE as a promising eco-friendly botanical fungicide for managing C. scovillei infections in chili peppers.

Abstract Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m2) and HSCT were associated with greater recovery of renal function at 12 months of follow-up.

Abstract Recent studies have suggested that Transposable Elements (TEs) residing in introns frequently splice into and alter primary gene-coding transcripts. To re-examine the exonization frequency of TEs into protein-coding gene transcripts, we re-analyzed a Drosophila neuron circadian rhythm RNAseq dataset and a deep long RNA fly midbrain RNAseq dataset using our Transposon Insertion and Depletion Analyzer (TIDAL) program. Our TIDAL results were able to predict several TE insertions from RNAseq data that were consistent with previous published studies. However, we also uncovered many discrepancies in TE-exonization calls, such as reads that mainly support intron retention of the TE and little support for chimeric mRNA spliced to the TE. We then deployed rigorous genomic DNA-PCR (gDNA-PCR) and RT-PCR procedures on TE-mRNA fusion candidates to see how many of bioinformatics predictions could be validated. By testing a w1118 strain from which the deeper long RNAseq data was derived and comparing to an OreR strain, only 9 of 23 TIDAL candidates (

Abstract Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo a poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating that wild-type-expressing cells normalize transcriptional homeostasis. These results advance our understanding of RTT progression and treatment.

Abstract Background Globally, mental health challenges are common among school-going adolescents, with a prevalence of 50.2% and 43.6% for depression and anxiety disorders, respectively. In Northeastern Uganda, a prevalence of 26.6% and 8.6% for anxiety and depressive disorders respectively were reported among children. School-going adolescents are at higher risk of developing these mental health challenges and this could be worsened by natural disasters like landslides. We aimed to determine the prevalence and factors contributing to mental health challenges (having at least one of following; depression, anxiety, anger, disruptive behaviour and social concept) among school adolescents in the Manafwa Watershed area. Methods This was a cross-sectional study in 3 districts of the Manafwa watershed area (Bududa, Manafwa, and Butaleja). We selected school-going adolescents aged 13-18 years because of the nature of study tools. Mental health challenges (anxiety, depression, anger, disruptive behaviour and self-concept) were assessed using the Beck Youth Inventory-II. Descriptive statistics and inferential analysis were performed to determine factors associated with mental health challenges. Results A total of 762 adolescents participated, with a median age of 17 years (interquartile range =16–17 years). More than half of the students were females. The prevalence of mental health challenges was 65% with a (confidence interval) = 54.0% — 75.0%; the majority 44% of the participants had anxiety, and 31% had disruptive behaviour. Families with more than five children [adjusted odds ratio = 1.18, 95% confidence interval= 1.08—1.29, p value =

Abstract Heatwaves (HWs) pose a severe threat to human and ecological systems. Here we assess the projected changes in heatwaves over Latin America using bias corrected high-resolution regional climate simulations under two Representative Concentration Pathway scenarios (RCPs). Heatwaves are projected to be more frequent, long-lasting, and intense in the mid-century under both RCP2.6 and RCP8.5 scenarios, with severe increases under the RCP8.5 scenario. Even under the low emissions scenario of RCP2.6, the frequency of heatwaves doubles over most of the region. A three- to tenfold rise in population exposure to heatwave days is projected over Central and South America, with climate change playing a dominant role in driving these changes. Results show that following the low emission pathway would reduce 57% and 50% of heatwave exposure for Central and South American regions respectively, highlighting the need to control anthropogenic emissions and implement sustainable practices.

Abstract Peptides are promising drug development frameworks that have been hindered by intrinsic undesired properties including hemolytic activity. We aim to get a better insight into the chemical space of hemolytic peptides using a novel approach based on network science and data mining. Metadata networks (METNs) were useful to characterize and find general patterns associated with hemolytic peptides, whereas Half-Space Proximal Networks (HSPNs), represented the hemolytic peptide space. The best candidate HSPNs were used to extract various subsets of hemolytic peptides (scaffolds) considering network centrality and peptide similarity. These scaffolds have been proved to be useful in developing robust similarity-based model classifiers. Finally, using an alignment-free approach, we reported 47 putative hemolytic motifs, which can be used as toxic signatures when developing novel peptide-based drugs. We provided evidence that the number of hemolytic motifs in a sequence might be related to the likelihood of being hemolytic.

Abstract Background Informed consent (IC) is a fundamental principle in medical ethics that upholds respect for patient autonomy. Although widely applied in healthcare, its feasibility and implementation in herbal medicine have been underexplored. This study therefore aimed to explore the practices and attitudes of herbalists regarding informed consent. Methods To achieve these objectives, a qualitative cross-sectional study was conducted from June to December 2020. Twenty-one in-depth interviews with herbalists and four key informant interviews with leaders of the different traditional medicine organizations were conducted. The data were analyzed thematically using NVivo version 12 software. Results Sixteen of the twenty-one participants acquired oral herbal medicine knowledge from their relatives. Although a positive inclination toward obtaining IC was evident, the focus was on disclosing basic information. Discussions of alternative treatments and herbal specifics were less frequent. Disease management decisions often involve shared responsibility within families or societies. Documented IC procedures are rare among herbalists, who deem consent forms unnecessary, although they recognize the potential benefits of IC in fostering trust and professionalism. Challenges hindering IC implementation included regulatory gaps, inadequate skills, and the absence of mechanisms to protect the intellectual property rights of herbal medicine. Conclusion This study illuminates how educational, cultural, familial, and regulatory factors influence herbalists’ practices and attitudes toward informed consent.

Abstract Introduction Sub-Saharan Africa has a high burden of HIV, particularly among female sex workers (FSW) and men who have sex with men (MSM). Future clinical trials to evaluate vaccines and other interventions to prevent HIV will need to enroll populations with high HIV incidence. We conducted an observational study of HIV incidence among men and women with multiple sexual partners—including MSM and FSW—in Maputo, Mozambique, in order to prepare the country to conduct future efficacy trials of candidate HIV vaccines and other HIV prevention products. Methods We conducted a prospective observational HIV incidence study in Maputo, Mozambique, that enrolled adults aged 18–35 years, without HIV, who had two or more sexual partners in the preceding three months. Recruitment strategies prioritized participation of MSM and FSW. Participants were followed for 24 months with HIV-1 testing every 3 months and staff-administered behavioral questionnaires every 6 months. Cox proportional hazard modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV acquisition. Results From January 2014 to October 2017, 505 adults without HIV were enrolled with median age of 21 years (interquartile range:19–24); 41% were female and 82% were single. There were 19 HIV seroconversions (10 female and 9 male) during 943 person-years (PY) of observation (overall HIV incidence 2.02/100PY; 95%CI 1.21–3.15). The highest HIV incidence was observed among sex workers (2.08/100PY; 95%CI 0.25–7.52) and MSM (19.18/100PY; 95%CI 3.96–56.06). Increased hazard of incident HIV was observed among participants who were MSM (HR = 27.95, 95%CI 4.39–117.94), p = 0.0004), reported three or more sexual partners at enrollment (HR = 7.39, 95%CI 1.64–33.25, p = 0.009), and indicated ever having a sexual partner living with HIV (HR = 9.64, 95%CI 2.23–41.71, p = 0.002). Conclusion Our findings may inform inclusion criteria for upcoming clinical trials of HIV prevention interventions, including vaccine candidates, which may prioritize enrollment of MSM, people with more than three sexual partners, and people with sexual partners who are living with HIV. These same populations are in need of further intervention to reduce HIV incidence.

Campylobacteriosis and antimicrobial resistance (AMR) are global public health concerns. Africa is estimated to have the world’s highest incidence of campylobacteriosis and a relatively high prevalence of AMR in Campylobacter spp. from humans and animals. Few studies have compared Campylobacter spp. isolated from humans and poultry in Africa using whole-genome sequencing and antimicrobial susceptibility testing. We explored the population structure and AMR of 178 Campylobacter isolates from East Africa, 81 from patients with diarrhea in Kenya and 97 from 56 poultry samples in Tanzania, collected during 2006–2017. Sequence type diversity was high in both poultry and human isolates, with some sequence types in common. The estimated prevalence of multidrug resistance, defined as resistance to >3 antimicrobial classes, was higher in poultry isolates (40.9%, 95% credible interval 23.6%–59.4%) than in human isolates (2.5%, 95% credible interval 0.3%–6.8%), underlining the importance of antimicrobial stewardship in livestock systems.

Abstract Aims Clinical pathways have been shown to improve outcomes in patients with heart failure (HF). Although patients with HF often have a cardiac implantable electronic device, few studies have reported the utility of device‐derived risk scores to augment and organize care. TriageHF Plus is a device‐based HF clinical pathway (DHFP) that uses remote monitoring alerts to trigger structured telephone assessment for HF stability and optimization. We aimed to evaluate the impact of TriageHF Plus on hospitalizations and describe the associated workforce burden. Methods and results TriageHF Plus was a multi‐site, prospective study that compared outcomes for patients recruited between April 2019 and February 2021. All alert‐triggered assessments were analysed to determine the appropriateness of the alert and the workload burden. A negative‐binomial regression with inverse probability treatment weighting using a time‐matched usual care cohort was applied to estimate the effect of TriageHF Plus on non‐elective hospitalizations. A post hoc pre‐COVID‐19 sensitivity analysis was also performed. The TriageHF Plus cohort (n = 443) had a mean age of 68.8 ± 11.2 years, 77% male (usual care cohort: n = 315, mean age of 66.2 ± 14.5 years, 65% male). In the TriageHF Plus cohort, an acute medical issue was identified following an alert in 79/182 (43%) cases. Fifty assessments indicated acute HF, requiring clinical action in 44 cases. At 30 day follow‐up, 39/66 (59%) of initially symptomatic patients reported improvement, and 20 (19%) initially asymptomatic patients had developed new symptoms. On average, each assessment took 10 min. The TriageHF Plus group had a 58% lower rate of hospitalizations across full follow‐up [incidence relative ratio: 0.42, 95% confidence interval (CI): 0.23–0.76, P = 0.004]. Across the pre‐COVID‐19 window, hospitalizations were 31% lower (0.69, 95% CI: 0.46–1.04, P = 0.077). Conclusions These data represent the largest real‐world evaluation of a DHFP based on multi‐parametric risk stratification. The TriageHF Plus clinical pathway was associated with an improvement in HF symptoms and reduced all‐cause hospitalizations.

This article examines the legislative, investment and policy environment that the Zimbabwean state is spearheading to transition the country from an overreliance on fossil fuels in response to the drawbacks of climate change. The need for this energy transition has become even more urgent due to decreasing water levels that can no longer sustain the country’s hydroelectric power outputs. A transition to other renewable energy sources and biofuels will lower the country’s carbon emissions. The article observes that while a lack of capital in large part hinders the country’s energy transition to invest in big renewable energy projects, the few small-scale projects underway are very opaque, (occasionally) transient and indistinct to the point of obscuring many potential benefits for the country’s citizens. This article relies on a review of primary material and sources from various repositories and a thorough review of secondary literature.

Improvements in clinical assessment have occurred since the last published recommendations on the diagnosis and treatment of acute promyelocytic leukemia in 2013. Here, a committee of specialists of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy presents a comprehensive review on the current knowledge, focusing on the advances in diagnosis, risk assessment, and frontline and salvage therapy. The concept of urgent diagnosis is explored as well as the management of critical situations such as coagulopathy and differentiation syndrome. Recent adjustments in risk stratification based on white blood cell counts only are presented together with the incorporation of chemo-free regimens for non-high-risk patients. Special conditions such as acute promyelocytic leukemia in children, the elderly and pregnant women are discussed. Finally, acute promyelocytic leukemia is presented as a highly curable disease because of the real possibility of targeted therapy towards differentiation, and, paradoxically, as a serious and urgent condition that deserves prompt recognition and management to avoid early mortality.

Abstract Background Hybrids are expected to show greater phenotypic variation than their parental species, yet how hybrid phenotype expression varies with genetic distances in closely-related parental species remains surprisingly understudied. Here, we investigate pelage and morphometric trait variation in anthropogenic hybrids between four species of Brazilian Callithrix marmosets, a relatively recent primate radiation. Marmoset species are distinguishable by pelage phenotype and morphological specializations for eating tree exudates. In this work, we (1) describe qualitative phenotypic pelage differences between parental species and hybrids; (2) test whether significant quantitative differences exist between parental and hybrid morphometric phenotypes; and (3) determine which hybrid morphometic traits show heterosis, dysgenesis, trangression, or intermediacy relative to the parental trait. We investigated cranial and post-cranial morphometric traits, as most hybrid morphological studies focus on the former instead of the latter. Finally, we estimate mitogenomic distances between marmoset species from previously published data. Results Marmoset hybrid facial and overall body pelage variation reflected novel combinations of coloration and patterns present in parental species. In morphometric traits, C. jacchus and C. penicillata were the most similar, while C. aurita was the most distinct, and C. geoffroyi trait measures fell between these species. Only three traits in C. jacchus x C. penicillata hybrids showed heterosis. We observed heterosis and dysgenesis in several traits of C. penicillata x C. geoffroyi hybrids. Transgressive segregation was observed in hybrids of C. aurita and the other species. These hybrids were also C. aurita-like for a number of traits, including body length. Genetic distance was closest between C. jacchus and C. penicillata and farthest between C. aurita and the other species. Conclusion We attributed significant morphometric differences between marmoset species to variable levels of morphological specialization for exudivory in these species. Our results suggest that intermediate or parental species-like hybrid traits relative to the parental trait values are more likely in crosses between species with relatively lesser genetic distance. More extreme phenotypic variation is more likely in parental species with greater genetic distance, with transgressive traits appearing in hybrids of the most genetically distant parental species. We further suggest that fewer developmental disturbances can be expected in hybrids of more recently diverged parental species, and that future studies of hybrid phenotypic variation should investigate selective pressures on Callithrix cranial and post-cranial morphological traits.

Abstract Background The Health Belief Model (HBM) is a widely utilised framework for understanding vaccination behaviour against COVID-19. This study assessed the acceptance of COVID-19 vaccine booster doses in Ghana and identified predictors using HBM domains, including perceived susceptibility, severity, benefits, barriers, self-efficacy, and cues to action. Additionally, it examined the sources of information about COVID-19 vaccines. Methods We employed a cross-sectional quantitative design, using convenient and snowball sampling methods to recruit participants. Between March 20 and May 10, 2023, 822 Ghanaians completed a predesigned self-administered online survey via commonly used social media platforms (WhatsApp, Facebook, X (Twitter), and LinkedIn). The study used a binary logistic regression to predict COVID-19 booster dose acceptance. Results The respondents had a mean age of 29.3 ± 6.2, with 55.5 being males, 53.0% being single/never married, 93.7% having tertiary education, 83.0% being Christians, 59.1% were healthcare workers, 57.8% residing in urban areas, 95.5% having no chronic disease, 90.6% reporting negative COVID-19 history, and 78.3% reporting no reported relative/friend infected with COVID-19. The study showed that 81.1% [95% confidence interval (CI) = 78.4 − 83.8%] of respondents received the COVID-19 vaccine, and 58.3% [95% CI = 54.2 − 62.5%] of respondents were willing to accept the COVID-19 booster dose. The main reasons for non-acceptance of COVID-19 vaccine booster doses were personal reasons (41.7%) and experienced side effects or fear of side effects (32.4%). Regression analysis revealed that perceived benefits and perceived barriers (specifically worrying about serious risk factors) were the significant predictors of accepting COVID-19 booster doses in Ghana. Conclusions Many respondents were willing to receive the COVID-19 booster dose. Personal reasons, fear of side effects, and experienced side effects were the main reasons for refusing COVID-19 booster doses. Perceived benefits and perceived barriers predicted COVID-19 booster dose acceptance in Ghana. Policymakers should consider these factors in designing public health interventions to increase the patronage of COVID-19 booster doses.

As modern systems become more complex, their control strategy no longer relies only on measurement data from probes; it also requires information from mathematical models for non-measurable places. On the other hand, those mathematical models can lead to unbearable computation times due to their own complexity, making the control process non-viable. To overcome this problem, it is possible to implement any kind of surrogate model that enables the computation of such estimates within an acceptable time frame, which allows for making decisions. Using a Physics-Informed Neural Network as a surrogate model, it is possible to compute the temperature distribution at each time step, replacing the need for running direct numerical simulations. This approach enables the use of a Deep Reinforcement Learning algorithm to train a control strategy. On this work, we considered a one-dimensional heat conduction problem, in which temperature distribution feeds a control system. Such control system has the objective of reacing and maintaining constant temperature value at a specific location of the 1D problem by activating a heat source; the desired location somehow cannot be directly measured so, the PINN approach allows to estimate its temperature with a minimum computational workload. With this approach, the control training becomes much faster without the need of performing numerical simulations or laboratory measurements.

Abstract Background In Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART. The aim of this study was to determine the incidence and predictors of virological failure among CALHIV on second-line ART in Uganda. Methodology This was a retrospective cohort study of all CALHIV aged 0-19 years who were switched to second-line ART regimen between June 2010 and June 2019 at the Baylor Uganda Centre of Excellence clinic. Data was analysed using STATA 14. Cumulative incidence curves were used to assess incidence of virological failure. Factors associated with virological failure were identified using sub-distributional hazard regression analysis for competing risks considering death, transfer out and loss to follow-up as competing risks. Results Of 1104 CALHIV, 53% were male. At switch to Protease Inhibitor (PI) based second-line ART, majority (47.7%) were aged 5 – 9 years,56.2% had no/mild immune suppression for age while 77% had viral load copies < 100,000 copies/mL. The incidence of virological failure on second-line ART regimen among CALHIV was 3.9 per 100 person-years (PY) with a 10-year cumulative incidence rate of 32%. Factors significantly associated with virological failure were age 10 – 19 years (HR 3.2, 95% 1.6 – 6.2, p < 0.01) and HIV viral load count > 100,000 copies/mL (HR 2.2, 95% CI 1.5 – 3.1), p < 0.01) prior to second-line ART switch. Conclusion Treatment outcomes for children and adolescents on second-line ART are favourable with one third of them developing virological failure at 10 years of follow up. Adolescent age group and high HIV viral load at the start of second-line ART were significantly associated with virological failure on second-line ART. There is need to determine optimal strategies to improve ART treatment outcomes among adolescents with high viral load counts at second-line ART switch.

Abstract Background With the global rise in the elderly population, ensuring geriatric-friendly healthcare services is paramount. This study aimed to assess the current readiness of health facilities in Kampala City, Uganda, to provide geriatric-friendly care services. Methods We conducted a cross-sectional study in 35 health facilities (HF) including Private for-profit (PFP), Private not-for-profit, and public (government-run) facilities at different levels i.e., Health Centre III, Health Centre IV, and Hospitals, within Kampala City, Uganda. Data was collected using a self-administered health facility assessment tool. Facilities scoring 80–100 were classified as fully ready to offer geriatric-friendly care, 51–79 indicated moderate readiness, and 0–50 indicated low readiness. Results The overall readiness index (RI) across all facilities was low, 44.09 (SD ± 14.18). The National Referral Hospital (NRH), PFPs, and HFs in Kampala Central had the highest RI of 55.34. 47.63 and 51.09 respectively. The low readiness of HF to provide geriatric-friendly care was due to the low scores in leadership and governance (13.49), financing (19.29), human resource (42.66), and Health Management Information System (47.99) WHO building blocks. HCIVs had a higher readiness index than the other HF levels (Coefficient: 17.40, 95% CI: 4.16 to 30.64, p = 0.012). HFs in Kawempe had a significantly lower RI than those in Makindye and Kampala Central (Coefficient: -13.80, 95% CI: -24.48 to -3.11, p = 0.013). Conclusion The findings of our study indicate that public and private health facilities in Kampala City are not ready enough to provide geriatric-friendly care services.

Abstract Background There remain key knowledge gaps regarding HIV testing needs and priorities among refugee youth in low and middle-income country (LMIC) humanitarian settings. The HIV prevention cascade framework focuses on three domains (motivation, access, effective use) central to prevention uptake, yet is understudied in relationship to HIV testing, particularly among refugee youth. Uganda is an exemplar context to explore refugee youth HIV testing needs and priorities as it hosts 1.5 million refugees and is Africa’s largest refugee hosting nation. In this study, we explored perceptions and experiences regarding HIV testing among refugee youth living in Bidi Bidi refugee settlement, Uganda. Methods We conducted a community-based research study in Bidi Bidi Refugee Settlement, one of the world’s largest refugee settlements with over 195,000 residents. This qualitative study involved four focus groups (2 with young women, 2 with young men) with refugee youth aged 16–24 living in Bidi Bidi refugee settlement. We applied thematic analysis informed by the HIV prevention cascade to understand domains of motivation, access, and effective use that emerged as salient for HIV testing engagement. Results Participants (n = 40; mean age: 20 years, standard deviation: 2.2) included refugee young women (n = 20) and young men (n = 20), of whom 88% had a lifetime HIV test and 58% had ever heard of HIV self-testing. Participant discussions described HIV testing motivation was influenced by dimensions of: HIV treatment and testing knowledge; risk perception; positive and negative consequences of use; and social norms regarding gender and age. Access to HIV testing was shaped by: limited availability; distance and language barriers; confidentiality concerns; and affordability. Effective use of and engagement with HIV testing was related to HIV serostatus knowledge self-efficacy and in/equitable partner dynamics. Conclusions Complex, multi-level factors shape motivation for, access to, and effective use of HIV testing among refugee youth in Bidi Bidi. Findings align with the HIV prevention cascade framework that helps to identify gaps to inform intervention development with youth in humanitarian settings. HIV testing approaches tailored for refugee youth in contexts such as Bidi Bidi can foster HIV prevention and treatment literacy, gender equity, gender-based violence prevention, and intersectional stigma reduction.

This systematic literature review aimed to assess the methodological quality of user-centered usability evaluation of digital applications to promote citizens’ engagement and participation in public governance by (i) systematizing their purposes; (ii) analyzing the evaluation procedures, methods, and instruments that were used; (iii) determining their conformance with recommended usability evaluation good practices; and (iv) identifying the implications of the reported results for future developments. An electronic search was conducted on Web of Science, Scopus, and IEEE Xplore databases, and after a screening procedure considering predefined eligibility criteria, 34 studies were reviewed. These studies performed user-centered usability evaluation of digital applications related to (i) participatory reporting of urban issues, (ii) environmental sustainability, (iii) civic participation, (iv) urban planning, (v) promotion of democratic values, (vi) electronic voting, and (vii) chatbots. In terms of the methodological quality of the included studies, the results suggest that there is a high heterogeneity of the user-centered usability evaluation. Therefore, there is a need for recommendations to support user-centered usability evaluations of digital applications to promote citizens’ engagement and participation in public governance to improve the planning and conduction of future research.

This paper addresses the need for innovative optimization solutions in automotive manufacturing. Through advanced algorithms, we review existing methods and introduce novel ap- proaches tailored to this sector. Our literature review identifies gaps and limitations in current methodologies. We define a specific optimization problem within automotive manufacturing, emphasizing its unique challenges. Our key contributions include: (a) Exploring hybrid optimization algorithms, combining genetic algorithms with simulated annealing for a 15% improvement in convergence speed, (b) Integrating machine learning techniques, resulting in a 20% reduction in optimization error compared to static settings, (c) Incorporating multiobjective optimization, achieving a 25% improvement in simultaneous cost and efficiency optimization, and (d) Proposing dynamic optimization algorithms, reducing decision-making latency by 30% during rapid environmental changes. Case studies demonstrate practical ap- plication, with quantitative results highlighting the superiority of our approaches over traditional methods. Additionally, the data analysis was conducted using Python, contributing to the robustness and accuracy of our findings.

RESUMO A década de 70 é marcada pelo nascimento de uma tríplice crise: uma crise econômica, uma crise de política econômica e uma crise da teoria econômica até então esmônica. O crescimento acentuado da economia capitalista mundial, e a diminuição considerável da amplitude dos movimentos cíclicos, durante o pós-guerra, parecem ter validado os conceitos keynesianos que chegaram ao poder após a crise de 1929 e a subsequente Segunda Guerra Mundial. Em 1974-75 tudo mudou. A crise reapareceu com toda a sua profundidade, juntamente com um sentimento de ceticismo quanto à eficácia da intervenção do Estado. Ao mesmo tempo com toda sua força ressurgia a tese “liberal” e monetarista que havia sido destronada pelo impacto dos acontecimentos dos anos 30 e pela crítica de Keynes. O objetivo deste artigo é enquadrar-se no debate que existe hoje sobre a crise e a intervenção do Estado e propor uma interpretação das dificuldades econômicas desencadeadas pela crise de 1974-75, a partir dos elementos teóricos deixados por Marx.

Two independent barrier envelopes are the usual requirement used in most well operations to avoid catastrophic accidents. These are classified as primary – concerning preventing the occurrence of a kick, and secondary – concerning controlling the kick to avoid a blowout. Barrier envelopes consist of barrier elements, thus verifying the quality of these elements is fundamental. Barrier elements may be either redundant or mandatory, and these relationships are what constitute the barrier envelopes. In this work, we present a methodology to evaluate well safety by identifying existing barrier elements and barrier envelopes and mapping their relationships through the usage of graphs technique. This technique explicitly states the relationship between barriers and between them and envelopes. It enables a simpler visualization for well designers and allows the development of computer programs to control the safety and integrity of wells, both in the design phase and during drilling. 12 graphs are provided for a 4-phase well (conductor, surface, production, and drill-in), considering both the primary and secondary envelopes. Reasoning for constructing each graph is thoroughly provided. If these graphs are used, reliability values can then be assigned to each barrier element, which results in the reliability of entire barrier envelopes. This can be further extended to analyze the safety of each operation by applying the system to operational sequences and even comparing well designs.

Abstract Background There is limited research on the spatial distribution of eating disorders and the proximity to available eating disorder services. Therefore, this study investigates the distribution of eating disorders among adolescents and young adults in Ontario, Canada, with a specific focus on geographic disparities and access to publicly-funded specialized eating disorder services. Methods A community sample of 1,377 adolescents and young adults ages 16–30 across Ontario between November and December 2021 participated in this study and completed the Eating Disorder Examination Questionnaire. Utilizing Geographic Information System (GIS) technology, we mapped the geographic prevalence of eating disorders and examined proximity to specialized eating disorder services. Multiple linear and logistic regression analyses were utilized to determine the association between geographic region and eating disorder symptomatology. Additionally, t-tests were utilized to examine differences between time/distance to specialized services and clinical risk for eating disorders. Results Applying geospatial analysis techniques, we detected significant spatial clusters denoting higher eating disorder scores in rural areas and areas with fewer specialized services. Likewise, our findings report disparities between rural and urban areas, suggesting that rural regions exhibit elevated rates of eating disorders. There were no associations between distance/time to services and eating disorder symptomology. Conclusions The discrepancies in eating disorder symptomology between urban/rural may stem from stigma and unique socio-cultural contexts in rural communities. The study underscores the need for targeted intervention, including telehealth, in addressing the eating disorder challenges faced by adolescents and young adults in rural regions.

Abstract Many of the energy systems functioning across the developing world are poorly designed and largely inadequate to meet a country's commercial and domestic energy needs. This is especially so in Latin America, where poverty trends have been exacerbated by limited access to energy, which could be used towards supporting industrial and small-scale commercial activities. This has characterised the widespread trend of energy poverty. This phenomenon poses a major barrier towards achieving the UN Sustainable Development Goals (SDGs) and addressing climate change, since lack of access to reliable energy generation systems hinders the development of economic activities and limits the comfort of living conditions. This paper reports on a study aimed at catering to a better understanding of the challenges related to energy poverty in Latin America and identifying some of the tools that may be deployed to address them. The methodological procedures used were bibliometric analysis and survey. The main findings of this research evidence that reducing energy poverty in Latin American countries is crucial to alleviating household costs since a considerable part of family income is used to pay the energy needs. Less use of coal, greater access to electricity—including those from renewable generation—as well as the use of technologies and programs subsidized by governments would significantly contribute to increasing the Latin American citizens' quality of life and achieving the SDGs.

Abstract SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal–Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.

Abstract Current climate projections for mid-latitude regions globally indicate an intensification of wind-driven coastal upwelling due to warming conditions. The dynamics of mid-latitude coastal upwelling are marked by environmental variability across temporal scales, which affect key physiological processes in marine calcifying organisms and can impact their large-scale distribution patterns. In this context, marine invertebrates often exhibit phenotypic plasticity, enabling them to adapt to environmental change. In this study, we examined the physiological performance (i.e., metabolism, Thermal Performance Curves, and biomass and calcification rates) of individuals of the intertidal mollusk Chiton granosus, a chiton found from northern Peru to Cape Horn (5° to 55°S). Our spatial study design indicated a pattern of contrasting conditions among locations. The Talcaruca site, characterized by persistent upwelling and serving as a biogeographic break, exhibited lower pH and carbonate saturation states, along with higher pCO2, compared to the sites located to the north and south of this location (Huasco and Los Molles, respectively). In agreement with the spatial pattern in carbonate system parameters, long-term temperature records showed lower temperatures that changed faster over synoptic scales (1–15 days) at Talcaruca, in contrast to the more stable conditions at the sites outside the break. Physiological performance traits from individuals from the Talcaruca population exhibited higher values and more significant variability, along with significantly broader and greater warming tolerance than chitons from the Huasco and Los Molles populations. Moreover, marked changes in local abundance patterns over three years suggested population-level responses to the challenging environmental conditions at the biogeographic break. Thus, C. granosus from the Talcaruca upwelling zone represents a local population with wide tolerance ranges that may be capable of withstanding future upwelling intensification on the Southern Eastern Pacific coast and likely serving as a source of propagules for less adapted populations.

El estudio de costos catastróficos que experimentan las personas afectadas por tuberculosis realizado en Colombia durante la pandemia de COVID-19 trajo consigo la oportunidad de implementar encuestas telefónicas como medio para la recopilación de información. Lo anterior se constituye como una innovación metodológica en los estándares establecidos por la Organización Mundial de la Salud (OMS) que, para este tipo de estudios, suelen tener base en el empleo de encuestas cara a cara con los pacientes que acuden a las instalaciones de salud. El diseño del estudio, sus objetivos y metodología fueron adaptados del manual práctico para la realización de encuestas de costos de la tuberculosis de la OMS. Se seleccionaron 1 065 personas afectadas por tuberculosis como participantes del estudio, a quienes se les administró de manera telefónica el cuestionario estándar adaptado al contexto colombiano. Fue posible obtener datos estructurados sobre los costos directos e indirectos que enfrentan los pacientes con tuberculosis y sus familias; de manera general, se observó que todas las variables de recopilación alcanzaron una completitud mayor a 80%, con un tiempo promedio de encuesta de 40 minutos y una tasa de rechazo de 8%. La metodología de encuestas telefónicas desarrollada para determinar la línea base del estudio de costos catastróficos en Colombia resultó innovadora por el formato telefónico, que mantiene los estándares de información requerida para permitir estimaciones comparables a nivel internacional, y es un medio útil en la generación de resultados estandarizados en eventos en los cuales existe limitación para la realización de encuestas cara a cara.

Population upsurge in Gwagwalada increased water demand in the area, thereby stressing water resources in the area. Aquifer properties in parts of Gwagwalada in North-Central Nigeria were therefore investigated using resistivity and hydrogeological approaches. Static water level measurements of hand dug wells were used to determine the groundwater flow direction for the area which coincides with the North East-South West joint direction. Constant rate pumping test was adopted for the research and 10 boreholes were pumped. The weathered/fractured basement range from 7.5 m to 56.7 m. The transmissivity values in the area ranged from 0.35 m2/d to 3.63 m2/d while the hydraulic conductivity range from 0.045 m/d to 0.18 m/d. The Vertical Electrical Soundings (VES) were carried out on the area. The geoelectric sections revealed four to five layers and the longitudinal conductance varied from 0.11 Ω−1 to 0.37 Ω−1. The results of the investigation characterized the groundwater potential in the study area into low and moderate while the aquifer protective capacity into weak and moderate zones. The efficacy of resistivity and pumping test data in quantifying aquifer properties has been established in this study. The findings of this study shed light on the properties of ground water and aquifer protective capacity in the area, hence assist in the effective future groundwater resources exploitation.

Embryonal sarcoma of the liver (ESL) is a rare and aggressive neoplasm primarily affecting children, with its occurrence in adults being exceptionally rare. This case report details the presentation, diagnosis, and management of ESL in a 20-year-old patient, highlighting the challenges and strategic approaches required in managing such atypical presentations. The patient presented with progressive right upper quadrant abdominal pain and significant weight loss, with imaging revealing a large mixed-density mass in the right lobe of the liver. Despite the nonspecific clinical symptoms and normal tumor markers, advanced imaging techniques including MRI and CT scans played a pivotal role in the diagnostic process. The mass exhibited characteristics that led to a differential diagnosis of a possible benign condition; however, the decision for surgical resection was made based on the tumor's rapid growth and potential malignancy suggested by imaging. Histopathological examination postsurgery confirmed the diagnosis of ESL. This case illustrates the importance of considering ESL in the differential diagnosis of rapidly enlarging liver masses in adults, despite its rarity in this age group. The effective management of this case through surgical intervention without prior biopsy, due to the risk of tumor seeding, followed by adjuvant chemotherapy, reflects the critical need for a multidisciplinary approach. The outcomes from this case contribute to the existing knowledge base, providing insights into the complexities of diagnosing and treating adult cases of ESL and affirming the adaptability of pediatric protocols to adult patients.

The development of mining projects in the exploration and pre-feasibility stages involves challenges related to geological and processing heterogeneity and uncertainty due to variability in their primary and response attributes. Therefore, the objective of this research is to develop the geometallurgical model of the Bond work index. For this purpose, linear regression models were developed in Jupyter Notebook considering 790 samples of uniaxial compressive strength of rock (UCS), lithologies, mineral zones and Bond work index (BWi) in a porphyry copper deposit. The results indicate a directly proportional linear relationship between BWi and UCS, generating modeling with acceptable R2 performances between 0.76 and 0.90. In addition, the lithologies and ore zones in the deposit studied are relevant characteristics related to comminution. Finally, according to rock competence, the rock is classified as medium to hard, hard and very hard in the oxide, mixed and primary sulfide zones, respectively.

Introducción: Innumerables factores contribuyen en el tiempo a cambiar conductas relacionadas con el estilo de vida, la pandemia de COVID-19 no solo alteró las rutinas de los individuos, sino que también hizo cambios en los factores que influyen en sus condiciones crónicas. Objetivo: Conocer la percepción de los pacientes con enfermedades cardiometabólicas, con relación a las adaptaciones en su estilo de vida después del contagio por COVID-19. Materiales y Métodos: Estudio exploratorio con enfoque cualitativo, realizado con nueve pacientes diagnosticados con enfermedades cardiometabólicas y que resultaron positivos a COVID-19. La recolección se realizó a partir de entrevistas grabadas en audio semiestructurado y su contenido fue transcrito y procesado en el software IRAMUTEQ. Resultados: El discurso colectivo mostró que la contaminación masiva por coronavirus y, posteriormente, Long-COVID desencadenó muchos miedos y angustias, además de un aumento de los dolores musculares, cansancio y la falta de control de la presión arterial y/o la glucemia, impactando directamente en la rutina de vida diaria de los pacientes infectados, pero también hubo un despertar por cambios en el estilo de vida. Discusión: La complejidad de las experiencias relatadas por los pacientes infectados incide en el deseo de adoptar un estilo de vida saludable y la búsqueda de conocimiento. Conclusiones: El número de pacientes afectados por COVID-19 en sus fases aguda y prolongada es preocupante para la sociedad y los profesionales de la salud, siendo necesario ampliar estrategias que apunten a la calidad de la atención, buscando un adecuado seguimiento en las diferentes esferas de la atención.

Abstract Documentation of resources used in the indigenous diets are important for preservation of cultural heritage, biodiversity conservation, sustainability, and food systems resilience. In view of this, edible plants list, processing, values, and challenges associated to indigenous foods/dishes, and beverages of Mogoditshane, Mmopane and Metsimotlhabe villages, Botswana were investigated through face-to-face interview and focus group discussion (FGD). Fifty-four (54) wild edible plants, most available after rains were documented. Fruits, roots, tubers, nuts, and leaves of wild edible plants are used in different forms some as diet recipes, snacks, herbal tea, substrates, and as an inoculum source for fermented products. For some, medicinal value was reported. Among the domesticated crops, beans, maize, sorghum, watermelon, cooking melons, sweet reed, ditloo, letlhodi, makgomane, groundnuts, morogo and millets were mentioned. Among indigenous beverages, bojalwa ja setswana (traditional sorghum beer) and khadi were widely mentioned. To some products, food safety and taboos challenge indicated. Because of high temperature and low rainfall, availability of some edible plants was indicated scarce. To some products mould spoilage from inadequately dried products, presence of insects/pests and soil impurities were challenging. Some beans and cereal grains were taking long time to cook leading to consumption of energy. In Mogoditshane village, because of conurbation to Gaborone city, limited land for farming, crop production was low resulting into life-style changes toward western culture diets. Reluctance to collect wild foods from bush was challenging for young generation. Most indigenous diets consumed are low in sugar and fat, but are wholesome like (whole grains, with dietary fibers, vitamins, and minerals) with high potential for diet diversifications. Even though, most indigenous foods/beverages are still consumed, there are worries that young generation has limited knowledge and skills to process. The communities have indicated that unlike old days relying on indigenous foods, these days they buy imported processed foods and beverages from supermarkets.

Abstract Cytidine deaminase (CDA) converts cytidine and deoxycytidine into uridine and deoxyuridine as part of the pyrimidine salvage pathway. Elevated levels of CDA are found in pancreatic tumors and associated with chemoresistance. Recent evidence suggests that CDA has additional functions in cancer cell biology. In this work, we uncover a novel role of CDA in pancreatic cancer cell metabolism. CDA silencing impairs mitochondrial metabolite production, respiration, and ATP production in pancreatic cancer cells, leading to a so-called Pasteur effect metabolic shift towards glycolysis. Conversely, we find that CDA expression promotes mitochondrial biogenesis and oxidative phosphorylation, independently of CDA deaminase activity. Furthermore, we observe that patient primary cells overexpressing CDA are more sensitive to mitochondria-targeting drugs. Collectively, this work shows that CDA plays a non-canonical role in pancreatic cancer biology by promoting mitochondrial function, which could be translated into novel therapeutic vulnerabilities.

A new genus, Nilssondytes gen. nov., is described for a unique new species, Nilssondytes diversus sp. nov., from Venezuela. This paper corrects an inadvertent mistake in a paper by the authors (Miller et al. 2024) in which the collection of deposition of the holotype of the species was not indicated making the new species unavailable which, therefore, made the new genus unavailable. A review of the relevant parts of the International Code of Zoological Nomenclature is included. Diagnostic features of the new genus and species are discussed and illustrated.

Abstract The gut microbiota and its secreted metabolites play a significant role in cardiovascular and musculoskeletal health and diseases. The dysregulation of the intestinal microbiota poses a significant threat to cardiovascular and skeletal muscle well-being. Nonetheless, the precise molecular mechanisms underlying these changes remain unclear. Furthermore, microgravity presents several challenges to cardiovascular and musculoskeletal health compromising muscle strength, endothelial dysfunction, and metabolic changes. The purpose of this review is to critically examine the role of gut microbiota metabolites on cardiovascular and skeletal muscle functions and dysfunctions. It also explores the molecular mechanisms that drive microgravity-induced deconditioning in both cardiovascular and skeletal muscle. Key findings in this review highlight that several alterations in gut microbiota and secreted metabolites in microgravity mirror characteristics seen in cardiovascular and skeletal muscle diseases. Those alterations include increased levels of Firmicutes/Bacteroidetes (F/B) ratio, elevated lipopolysaccharide levels (LPS), increased in para-cresol (p-cresol) and secondary metabolites, along with reduction in bile acids and Akkermansia muciniphila bacteria. Highlighting the potential, modulating gut microbiota in microgravity conditions could play a significant role in mitigating cardiovascular and skeletal muscle diseases not only during space flight but also in prolonged bed rest scenarios here on Earth.

Abstract Perinatal depression (PND) affects up to 20% of women and is associated with significant impairment and disability in affected women. In addition, perinatal depression is associated with broader public health and multigenerational consequences. Innovative approaches are needed to reduce the burden of perinatal depression through identification, tracking, and treatment of depressive symptoms during the perinatal period. This study is a randomized clinical trial comparing the relative efficacy of a multi-tiered system of care, Screening and Treatment of Anxiety and Depression (STAND) to perinatal care delivered by a reproductive psychiatrist in reducing symptoms of depression and anxiety. A sample of 167 individuals was randomized between week 28 of pregnancy and 6 months postpartum. A secondary aim compares the original online therapy intervention used in the first half of the study to a newer online therapy program used in the second half of the study for individuals assigned to the STAND treatment. The study measures, intervention groups, and analysis methods are described, as well as expected implications. The findings from this study may improve the methods for tracking symptom changes over time, monitoring treatment response, and providing personalized care for individuals with PND. As such, this study may improve the lives of patients with PND and their families and lower the related health care costs to society. Trial registration NCT: 9/24/2021 NCT direct link: https://www.clinicaltrials.gov/study/NCT05056454?term=NCT05056454&rank=1&a=1 .

Abstract Introduction Globally, healthcare providers (HCPs), hospital administrators, patients and their caretakers are increasingly confronted with complex moral, social, cultural, ethical, and legal dilemmas during clinical care. In high-income countries (HICs), formal and informal clinical ethics support services (CESSs) have been used to resolve bioethical conflicts among HCPs, patients, and their families. There is limited evidence about mechanisms used to resolve these issues as well as experiences and perspectives of the stakeholders that utilize them in most African countries including Uganda. Methods This phenomenological qualitative study utilized in-depth interviews (IDIs) and focus group discussions (FGDs) to collect data from Uganda Cancer Institute (UCI) staff, patients, and caretakers who were purposively selected. Data was analyzed deductively and inductively yielding themes and sub-themes that were used to develop a codebook. Results The study revealed there was no formal committee or mechanism dedicated to resolving ethical dilemmas at the UCI. Instead, ethical dilemmas were addressed in six forums: individual consultations, tumor board meetings, morbidity and mortality meetings (MMMs), core management meetings, rewards and sanctions committee meetings, and clinical departmental meetings. Participants expressed apprehension regarding the efficacy of these fora due to their non-ethics related agendas as well as members lacking training in medical ethics and the necessary experience to effectively resolve ethical dilemmas. Conclusion The fora employed at the UCI to address ethical dilemmas were implicit, involving decisions made through various structures without the guidance of personnel well-versed in medical or clinical ethics. There was a strong recommendation from participants to establish a multidisciplinary clinical ethics committee comprising members who are trained, skilled, and experienced in medical and clinical ethics.

Abstract Objective Post-ICU survivors face higher mortality and often require costly rehabilitation or palliative care, such as occupational therapy, physiotherapy and hospice. However, there is a lack of data quantifying the demand for these services, particularly in developing countries like Uganda. Therefore, this prospective cohort study aimed to investigate the 90-day mortality rate, functional status, and mortality risk factors among 121 ICU patients discharged from three tertiary hospital ICUs in Uganda by tracking their vital and physical functional status for three months with follow-ups on days 30, 60, and 90, and identifying risk factors through Cox regression. Results The study revealed that 18 out of 121 ICU patients (14.88%, 95% CI: 9.52-22.51%) died within 90 days post-discharge, while 36.36% achieved normal physical functional status. Factors associated with higher 90-day mortality included raised intracranial pressure (HR 1.92, 95% CI: 1.76–2.79, p = 0.04), acute kidney injury (HR 4.13, 95% CI: 2.16–7.89, p