Browse Articles

Author Correction: Sb2S3-templated synthesis of sulfur-doped Sb-N-C with hierarchical architecture and high metal loading for H2O2 electrosynthesis

Knockout of the ING5 epigenetic regulator confirms roles in stem cell maintenance and tumor suppression in vivo

INhibitor of Growth (ING1-5) proteins are epigenetic readers that target histone acetyltransferase (HAT) or histone deacetylase (HDAC) complexes to the H3K4Me3 mark of active transcription. ING5 targets Moz/Morf and HBO1 HAT complexes that alter acetylation of H3 and H4 core histones, affecting gene expression. Previous experiments in vitro indicated that ING5 functions to maintain stem cell character in normal and in cancer stem cells. Here we find that CRISPR/Cas9 ING5 knockout (KO) mice are sub-fertile but show no decrease in lifespan or ability to heal wounds despite indications of depleted stem cell pools in several tissues. ING5 KO mouse embryo fibroblasts accumulate in G2 of the cell cycle, have high levels of abnormal nuclei and show high basal levels of the γH2AX indicator of DNA damage. KO animals also develop severe dermatitis at a 5-fold higher rate that wild-type littermates. Consistent with ING5 serving a tumor suppressive role, ING5 KO mice developed germinal centre diffuse large B-cell lymphomas at a rate 6-fold higher than control mice at 18 months of age. These data suggest that ING5 functions in vivo to maintain stem cell character in multiple organs, that reduction of stem cell populations is not limiting for murine lifespan and that like a subset of other ING family members, ING5 functions as a tumor suppressor in hematopoietic cells in vivo.

Author Correction: Ligand-tuning copper in coordination polymers for efficient electrochemical C–C coupling

Achieving the state of Georgia 25% HIV incidence reduction target among men who have sex with men in Atlanta through expanded use of multimodal pre-exposure prophylaxis: A mathematical model

The US faces substantial demographic and geographic disparities in both HIV burden and access to pre-exposure prophylaxis (PrEP), an effective strategy to prevent HIV acquisition. Long-acting cabotegravir (CAB) is a novel, injectable PrEP option which demonstrated superior reduction in risk of HIV acquisition compared to daily-oral PrEP in the HPTN083 trial. We modelled the impact of increased PrEP initiations and the introduction of long-acting CAB on HIV incidence among men who have sex with men (MSM) in Atlanta, Georgia, a population with a high burden of HIV. The Georgia Department of Public Health has set an ambitious 25% HIV incidence reduction target, which could be reached with a daily-oral PrEP coverage of 42.2%. However, the target could be achieved at lower levels of PrEP coverage (34.6%) if a mix of PrEP modalities was used, such as an equal split of long-acting CAB PrEP and daily-oral PrEP. Our results clearly demonstrate that broadening access to new PrEP options has the potential to facilitate the achievement of public health HIV incidence reduction goals at plausible levels of PrEP coverage.

Author Correction: Interfacial friction enabling ≤20 μm thin free-standing lithium strips for lithium metal batteries

Efficacy of pulmonary surfactant with budesonide in premature infants: A systematic review and meta-analysis

Pulmonary surfactant (PS) is one of the main treatment for neonates with respiratory distress syndrome (RDS). Budesonide has recently been studied as an additional treatment in such cases, but there is limited evidence supporting this. This study was implemented to determine the efficacy of PS combined with budesonide in premature infants. To achieve this, we conducted a systematic review and meta-analysis of randomized controlled trials by searching PubMed, Scopus, Embase, and the Cochrane Library from inception until July 12, 2024. We utilized a random-effects model to calculate the risk ratio and mean differences (MDs) with 95% confidence intervals (CIs) for the clinical outcomes of PS with budesonide versus PS alone. We used the GRADE approach to assess the quality of the evidence. We included 26 randomized controlled trials with a total of 2701 patients in the analysis. Treatments of PS with budesonide and PS alone were compared in all trials. PS with budesonide reduced bronchopulmonary dysplasia (BPD) incidence (risk ratio, 0.61; 95% CI, 0.51, 0.73), duration of mechanical or invasive mechanical ventilation (MD, −2.21 days; 95% CI, −2.72, −1.71), duration requiring oxygen (MD, −5.86 days; 95% CI, −8.44, −3.29), and hospitalization time (MD, −5.61 days; 95% CI, −8.65, −2.56). These results were based on low to very low evidence certainty. Only moderate-to-severe BPD or severe BPD showed a significant reduction when PS was used in conjunction with budesonide, a finding supported by moderate evidence certainty. Our study showed that the administration of PS with budesonide significantly improved respiratory outcomes, including the incidence of BPD, duration of mechanical or invasive mechanical ventilation, duration requiring oxygen, and hospitalization time in preterm infants, without short-term adverse drug events. However, the evidence certainty was mostly low to very low.

Catalytic acceptorless complete dehydrogenation of cycloalkanes

DigiLoCS: A leap forward in predictive organ-on-chip simulations

Digital twins, driven by data and mathematical modelling, have emerged as powerful tools for simulating complex biological systems. In this work, we focus on modelling the clearance on a liver-on-chip as a digital twin that closely mimics the clearance functionality of the human liver. Our approach involves the creation of a compartmental physiological model of the liver using ordinary differential equations (ODEs) to estimate pharmacokinetic (PK) parameters related to on-chip liver clearance. The objectives of this study were twofold: first, to predict human clearance values, and second, to propose a framework for bridging the gap between in vitro findings and their clinical relevance. The methodology integrated quantitative Organ-on-Chip (OoC) and cell-based assay analyses of drug depletion kinetics and is further enhanced by incorporating an OoC-digital twin model to simulate drug depletion kinetics in humans. The in vitro liver clearance for 32 drugs was predicted using a digital-twin model of the liver-on-chip and in vitro to in vivo extrapolation (IVIVE) was assessed using time series PK data. Three ODEs in the model define the drug concentrations in media, interstitium and intracellular compartments based on biological, hardware, and physicochemical information. A key issue in determining liver clearance appears to be the insufficient drug concentration within the intracellular compartment. The digital twin establishes a connection between the hardware chip structure and an advanced mapping of the underlying biology, specifically focusing on the intracellular compartment. Our modelling offers the following benefits: i ) better prediction of intrinsic liver clearance of drugs compared to the conventional model and ii )explainability of behaviour based on physiological parameters. Finally, we illustrate the clinical significance of this approach by applying the findings to humans, utilising propranolol as a proof-of-concept example. This study stands out as the biggest cross-organ-on-chip platform investigation to date, systematically analysing and predicting human clearance values using data obtained from various in vitro liver-on-chip systems. Accurate prediction of in vivo clearance from in vitro data is important as inadequate understanding of the clearance of a compound can lead to unexpected and undesirable outcomes in clinical trials, ranging from underdosing to toxicity. Physiologically based pharmacokinetic (PBPK) model estimation of liver clearance is explored. The aim is to develop digital twins capable of determining better predictions of clinical outcomes, ultimately reducing the time, cost, and patient burden associated with drug development. Various hepatic in vitro systems are compared and their effectiveness for predicting human clearance is investigated. The developed tool, DigiLoCs, focuses explicitly on accurately describing complex biological processes within liver-chip systems. ODE-constrained optimisation is applied to estimate the clearance of compounds. DigiLoCs enable differentiation between active biological processes (metabolism) and passive processes (permeability and partitioning) by incorporating detailed information on compound-specific characteristics and hardware-specific data. These findings signify a significant stride towards more accurate and efficient drug development methodologies.

Charge-transfer complexation of coordination cages for enhanced photochromism and photocatalysis

AbstractIntensified host-guest electronic interplay within stable metal-organic cages (MOCs) presents great opportunities for applications in stimuli response and photocatalysis. Zr-MOCs represent a type of robust discrete hosts for such a design, but their host-guest chemistry in solution is hampered by the limited solubility. Here, by using pyridinium-derived cationic ligands with tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (BArF−) as solubilizing counteranions, we report the preparation of soluble Zr-MOCs of different shapes (1-4) that are otherwise inaccessible through a conventional method. Enforced arrangement of the multiple electron-deficient pyridinium groups into one cage (1) leads to magnified positive electrostatic field and electron-accepting strength in favor of hosting electron-donating anions, including halides and tetraarylborates. The strong charge-transfer (CT) interactions activate guest-to-host photoinduced electron transfer (PET), leading to pronounced and regulable photochromisms. Both ground-state and radical structures of host and host-guest complexes have been unambiguously characterized by X-ray crystallography. The CT-enhanced PET also enables the use of 1 as an efficient photocatalyst for aerobic oxidation of tetraarylborates into biaryls and phenols. This work presents the solution assembly of soluble Zr-MOCs from cationic ligands with the assistance of solubilizing anions and highlights the great potential of harnessing host-guest CT for boosting PET-based functions and applications.

Regional disparities of full pentavalent vaccine uptake and the determinants in Ethiopia: Mapping and spatial analysis using the EDHS data

Background The full pentavalent (DPT-HepB-Hib) vaccination is the main strategy to prevent five communicable diseases in early childhood, especially in countries with huge communicable disease burdens like Ethiopia. Exploring spatial distributions and determinants of full pentavalent vaccination status in minor ecological areas in Ethiopia is crucial for creating targeted immunization campaigns and monitoring the advancement of accomplishing sustainable development goals. This study aimed to investigate the spatial disparities and determinants of full pentavalent vaccination among 12-23-month-old children in Ethiopia. Method The data on pentavalent vaccine uptake was found in the Ethiopian Health and Demographic Survey (EDHS, 2019). A two-stage cluster sampling method was applied to collect the EDHS data. The enumeration area was the primary sample unit while the household served as the secondary sampling unit. The geographical variations of full pentavalent vaccine uptake were explored using Quantum Geographic Information System (QGIS) software. The significant predictors of full pentavalent vaccination were identified using a simple logistic regression model through R version 4.1 software. Result The national full pentavalent vaccine uptake was 59.2%. The spatial distribution of full pentavalent vaccine uptake was not uniform in Ethiopia. Spatial cluster analysis revealed that most of low coverage regions for full pentavalent vaccine uptake were Afar, Somali, and Harari. The regions with the highest and lowest rates of vaccine uptake were Tigray and Harari region, respectively. Maternal age of 35–49 years (AOR = 3.42; 95% CI: 1.99, 5.87), and 25–34 years (AOR = 1.55; 95% CI: 1.17, 2.19), primary education attended (AOR = 1.51; 95%CI: 1.07, 2.11), richness wealth index (AOR = 1.96; 95% CI: 1.40, 2.75), birth order of 1–3 (AOR = 1.88; 95% CI: 1.19, 2.96), and delivery in the health facility (AOR = 3.41: 95% CI: 2.52, 4.61) were the determinants of full pentavalent vaccine uptake in Ethiopia. Conclusion Ethiopia’s full pentavalent vaccine uptake was far lower than the global target. Older maternal age, maternal education, wealth index, birth order, and giving birth in a health facility were the determinants of full pentavalent vaccine uptake. Special attention should be given to Afar, Somali, and Harari regions, to strengthen the vaccine uptake. Moreover, improved socioeconomic status and getting maternal health services during delivery are necessary to enhance vaccine uptake.

Near-infrared fluorogenic RNA for in vivo imaging and sensing

Correction: Robustness of performance during domain change in an esport: A study of within-expertise transfer

Spatial control of doping in conducting polymers enables complementary, conformable, implantable internal ion-gated organic electrochemical transistors

Abstract Complementary transistors are critical for circuits with compatible input/output signal dynamic range and polarity. Organic electronics offer biocompatibility and conformability; however, generation of complementary organic transistors requires introduction of separate materials with inadequate stability and potential for tissue toxicity, limiting their use in biomedical applications. Here, we discovered that introduction of source/drain contact asymmetry enables spatial control of de/doping and creation of single-material complementary organic transistors from a variety of conducting polymers of both carrier types. When integrated with the vertical channel design and internal ion reservoirs of internal ion-gated organic electrochemical transistors, we produced matched complementary IGTs (cIGTs) that formed high-performance conformable amplifiers with 200 V/V uniform gain and 2 MHz bandwidth. These amplifiers showed long-term in vivo stability, and their miniaturized biocompatible design allowed implantation in developing rodents to monitor network maturation. cIGTs expand the use of organic electronics in standard circuit designs and enhance their biomedical potential.

Retraction: Integrin-Mediated Signaling Induced by Simian Virus 40 Leads to Transient Uncoupling of Cortical Actin and the Plasma Membrane

Water, sanitation, handwashing, and nutritional interventions can reduce child antibiotic use: evidence from Bangladesh and Kenya

AbstractAntibiotics can trigger antimicrobial resistance and microbiome alterations. Reducing pathogen exposure and undernutrition can reduce infections and antibiotic use. We assess effects of water, sanitation, handwashing (WSH) and nutrition interventions on caregiver-reported antibiotic use in Bangladesh and Kenya, longitudinally measured at three timepoints among birth cohorts (ages 3–28 months) in a cluster-randomized trial. Over 50% of children used antibiotics at least once in the 90 days preceding data collection. In Bangladesh, the prevalence of antibiotic use was 10–14% lower in groups receiving WSH (prevalence ratio [PR] = 0.90 (0.82–0.99)), nutrition (PR = 0.86 (0.78–0.94)), and nutrition+WSH (PR = 0.86 (0.79–0.93)) interventions. The prevalence of using antibiotics multiple times was 26–35% lower in intervention arms. Reductions were largest when the birth cohort was younger. In Kenya, interventions did not affect antibiotic use. In this work, we show that improving WSH and nutrition can reduce antibiotic use. Studies should assess whether such reductions translate to reduced antimicrobial resistance.

Like milk on the stove: Healthcare professionals navigating uncertainty when caring for families with 22q11DS

Introduction 22q11 deletion syndrome (22q11DS) results from a microdeletion on chromosome 22 and is the most common microdeletion disorder in humans, affecting 1 in 2148 live births. Clinical manifestations vary widely among individuals and across different life stages. Effective management requires the involvement of a specialized multidisciplinary team. This study aims to explore the experiences of healthcare professionals in caring for the families of children with 22q11DS, focusing on their challenges, rewards, and coping strategies. Methods Data for this interview study were collected as part of a broader mixed methods research project aimed at enhancing the psychosocial well-being of children aged 3–15 years with 22q11DS and their families. The qualitative aspect of this study focused on capturing the experiences of healthcare professionals involved in their care, recruited purposively through collaborators and snowball sampling methods. Reflexive thematic analysis of semi-structured interviews was performed after verbatim transcription. Results Twenty healthcare providers from different specialties were interviewed. The majority had a working experience of more than 10 years and were part of a 22q11DS clinic. After data analysis, four themes (and many sub-themes) were identified that were all related to the topic of uncertainty: acknowledging uncertainty, sharing uncertainty, acting on uncertainty and coping with uncertainty. Many experts showed a sense of humbleness when caring for the families and most of the participants emphasized the role of peer support and multidisciplinary teams. Conclusion Our study reveals how healthcare professionals manage the uncertainty associated with 22q11DS, highlighting the importance of peer support and multidisciplinary team collaboration. Providers recognize the limits of their medical expertise and value the perspectives of families living with the condition. Their coping strategies play a critical role in handling uncertainty and suggest a need for further emphasis in the literature on the experiences of healthcare professionals dealing with rare diseases.

Author Correction: Twin-distortion modulated ultra-low coordination PtRuNi-Ox catalyst for enhanced hydrogen production from chemical wastewater

The impact of recognition, fairness, and leadership on employee outcomes: A large-scale multi-group analysis

In the dynamic field of organizational behavior, comprehending the determinants of employee engagement, burnout, and job satisfaction is pivotal. This research investigates the influence of various workplace factors, such as recognition, fairness, leadership, and workload, on these key employee outcomes. Utilizing Partial Least Squares Structural Equation Modeling (PLS-SEM) for analysis, the study examines data from 25,285 employees. The results indicate that recognition significantly boosts employee engagement, while fairness and involvement also positively contribute, albeit to a lesser extent. Transformational leadership plays a dual role, enhancing engagement and reducing burnout. Notably, workload overload presents a nuanced impact, affecting both engagement and burnout. The study additionally reveals the detrimental effect of technological disruption anxiety on job satisfaction. A significant finding from the Multi-Group Analysis (MGA) is the varying impact of these factors between the private and public sectors, particularly in the context of transformational leadership’s effect on burnout and the differential influence of workload on burnout. These insights are critical for formulating effective organizational strategies and policies, highlighting the need for customized recognition initiatives, equitable management approaches, and well-balanced workload allocation.

Bioinspired self-flowing wood chemical treatment

Getting back on track after treatment of cancer: A qualitative interview study of cancer survivors’ experiences

Objective An increasing number of people resumes life after cancer treatment. Although the (long-term) side-effects of cancer and its treatment can be significant, less is known about the impact on cancer survivors’ participation in daily life. The aim of this study was to explore the common experiences of cancer survivors in resuming life after treatment. Methods A semi-structured interview study was conducted among 22 cancer survivors having a favorable prognosis after treatment. Purposive sampling was used to select a variable sample in terms of diagnoses (e.g. breast cancer, colorectal cancer, melanoma), age (18–77 years), and time after diagnosis (0–7 years). Interviews were audio-taped, transcribed verbatim and analyzed in a thorough thematic analysis. Results Four main themes were identified. First, cancer survivors reported an emotional fallout episode to often follow treatment, which was characterized by a loss of direction and control due to discontinuation of medical care, decreased support from healthcare professionals and their social network, and an emotional set back. Second, survivors experienced challenges with getting back on track such as the impact of impaired physical and cognitive functions, and challenges and uncertainty related to work and finances. Third, in coping with changes and regaining trust they tried to find a balance between dealing with patient stigma and fear of recurrence on the one hand, and maintaining a positive mindset on the other hand. Fourth, the disease often led to re-evaluating values in life, health and work, which included realizing and accepting change and having a more conscious outlook on life. Conclusion In resuming life after treatment, cancer survivors experience several challenges and changes in values in different life domains that extend beyond the specific diagnosis. To improve supportive care, healthcare professionals should focus on the (changed) individual needs and values of survivors in the domains considered relevant to them.