Browse Articles

Data-driven de novo design of super-adhesive hydrogels

Redox-powered autonomous directional C–C bond rotation under enzyme control

Abstract Living biological systems rely on the continuous operation of chemical reaction networks. These networks sustain out-of-equilibrium regimes in which chemical energy is continually converted into controlled mechanical work and motion 1–3 . Out-of-equilibrium reaction networks have also enabled the design and successful development of artificial autonomously operating molecular machines 4,5 , in which networks comprising pairs of formally—but non-microscopically—reverse reaction pathways drive controlled motion at the molecular level. In biological systems, the concurrent operation of several reaction pathways is enabled by the chemoselectivity of enzymes and their cofactors, and nature’s dissipative reaction networks involve several classes of reactions. By contrast, the reactivity that has been harnessed to develop chemical reaction networks in pursuit of artificial molecular machines is limited to a single reaction type. Only a small number of synthetic systems exhibit chemically fuelled continuous controlled molecular-level motion 6–8 and all exploit the same class of acylation–hydrolysis reaction. Here we show that a redox reaction network, comprising concurrent oxidation and reduction pathways, can drive chemically fuelled continuous autonomous unidirectional motion about a C–C bond in a structurally simple synthetic molecular motor based on an achiral biphenyl. The combined use of an oxidant and reductant as fuels and the directionality of the motor are both enabled by exploiting the enantioselectivity and functional separation of reactivity inherent to enzyme catalysis.

StatModPredict: A user-friendly R-Shiny interface for fitting and forecasting with statistical models

Background Many disciplines, such as public health, rely on statistical time series models for real-time and retrospective forecasting efforts; however, effectively implementing related methods often requires extensive programming knowledge. Therefore, such tools remain largely inaccessible to those with limited programming experience, including students training in modeling, as well as professionals and policymakers seeking to forecast an epidemic’s trajectory. To address the need for accessible and intuitive forecasting applications, we present StatModPredict, an R-Shiny dashboard for conducting robust forecasting analysis utilizing auto-regressive integrated moving average (ARIMA), generalized linear models (GLM), generalized additive models (GAM), and Meta’s Prophet model. Methods StatModPredict supports robust real-time forecasting and retrospective model analysis, including fitting, forecasting, evaluation, visualization, and comparison of results from four popular models. After loading an incident time series data set into the interface, users can easily customize model parameters and forecasting options to obtain the desired output. Additionally, StatModPredict offers multiple editable figures for, but not limited to, the time series data, the forecasts, and model fit and forecast metrics. Users can also upload external forecasts produced elsewhere and evaluate their performance alongside the dashboard’s built-in models, thereby enabling direct comparisons. We provide a detailed demonstration of the dashboard’s features using publicly available annual HIV case data in the US. A video tutorial is available at https://www.youtube.com/watch?v=zgZOvqhvqw8. Conclusions By eliminating programming barriers, StatModPredict facilitates exploration and use by students training in forecasting, as well as professionals and policymakers aiming to forecast epidemic trajectories. Additionally, the flexibility in the required input data structure and parameter specification process extends the application of StatModPredict to any discipline that employs time series data. By offering this open-source interface, we aim to broaden access to forecasting tools, promote hands-on learning, and foster contributions from users across disciplines.

High-accuracy laser spectroscopy of $${{\bf{H}}}_{{\bf{2}}}^{{\boldsymbol{+}}}$$ and the proton–electron mass ratio

Abstract The molecular hydrogen ions (MHI) are three-body systems suitable for advancing our knowledge in several domains: fundamental constants, tests of quantum physics, search for new interparticle forces, tests of the weak equivalence principle1 and, once the anti-molecule $$\overline{p}\,\overline{p}\,{e}^{+}$$ p ¯ p ¯ e + becomes available, new tests of charge–parity–time-reversal invariance and local position invariance1–3. To achieve these goals, high-accuracy laser spectroscopy of several isotopologues, in particular $${{\rm{H}}}_{2}^{+}$$ H 2 + , is required4. Here we present a Doppler-free laser spectroscopy of a $${{\rm{H}}}_{2}^{+}$$ H 2 + rovibrational transition, achieving line resolutions as large as 2.2 × 1013. We accurately determine the transition frequency with 8 × 10−12 fractional uncertainty. We also determine the spin–rotation coupling coefficient with 0.1 kHz uncertainty and its value is consistent with the state-of-the-art theory prediction5. The combination of our theoretical and experimental $${{\rm{H}}}_{2}^{+}$$ H 2 + data allows us to deduce a new value for the proton-electron mass ratio m p/m e. It is in agreement with the value obtained from mass spectrometry and has 2.3 times lower uncertainty. From combined MHI, H/D and muonic H/D data, we determine the baryon mass ratio m d/m p with 1.1 × 10−10 absolute uncertainty. The value agrees with the directly measured mass ratio6. Finally, we present a match between a theoretical prediction and an experimental result, with a fractional uncertainty of 8.1 × 10−12. Both results indicate a notable confirmation of the predictive power of quantum theory and the absence of beyond-the-standard-model effects at these levels.

Biomimetic model for computing missing data imputation and inconsistency reduction in pairwise comparisons matrices

A biomimetic model is presented to compute missing data imputation and reduce inconsistencies in pairwise comparisons matrices. The proposed regeneration method emulates three primary phases of a biological process: identifying the most damaged areas (by identifying inconsistencies in the pairwise comparison matrix), cell proliferation (filling in missing data), and stabilization (optimization of global consistency). An iterative algorithm is employed to correct inconsistencies and compute missing data imputations within the pairwise comparison matrix. The results demonstrate that the biomimetic approach is robust and reliably converges to a consistent solution.

Do monetary incentives encourage local communities to collect and upload mosquito sound data using smartphones? A case study in the Democratic Republic of the Congo

Malaria is one of the deadliest vector borne diseases affecting sub-Saharan Africa. A suite of systems are being used to monitor and manage malaria risk and disease incidence, with an increasing focus on technological interventions that allow private citizens to remotely record and upload data. However, data collected by citizen scientists must be standardised and consistent if it is to be used for scientific analysis. Studies that aim to improve data collection quality and quantity have often included incentivisation, providing citizen scientists with monetary or other benefits for their participation in data collection. We tested whether monetary incentives enhance participation and data collection in a study trialling an acoustic mosquito sensor. Working with the community in two health areas in the Democratic Republic of Congo, we measured data collection participation, completeness, and community responses. Our results showed mixed responses to the incentive, with more participants interested in the social status and monetary value of the technology used than the monetary incentive itself. The effect of incentives on data collection varied over the course of the trial, increasing participation in the start of the trial but with no effect in the latter half of the trial. Feedback from participants showed that opinions on technology, research objectives, and incentives varied between communities, and was associated with differences in data collection quantity and quality, suggesting that differences in community interest in data collection and the incentives may be more important than the incentive value itself. These results suggest that though there is an initial benefit, extrinsic motivations do not override differences in intrinsic motivations over time, and enhanced communication and dialogue with participants may improve citizen science participation and attitudes.

Degradation of the Estrogen Receptor in Breast Cancer

Changes in the pulmonary surfactant in patients with mild to moderate COVID-19

Introduction Changes in the pulmonary surfactant have been seen in severe COVID-19, but data on mild to moderate COVID-19 is scarce. The aim of this study was to explore the protein and phospholipid profiles in the small airways in patients with mild to moderate COVID-19. Methods 29 cases with COVID-19 and 17 healthy controls were examined at baseline. 22 cases were re-examined at follow-up after recovery from COVID-19. Airwave oscillometry was performed and the biological material from the respiratory tract lining fluid was collected with the PExA (Particles in Exhaled Air) method. SOMAscan was used for the analysis of proteins, and liquid chromatography with tandem mass spectrometry (LC-MS/MS) for phospholipids. Results 95 lipid species belonging to 8 lipid classes, and 46 proteins were analysed. Relative amounts of 13 lipid species differed between cases and controls at baseline, and of 24 lipid species at follow-up. At follow-up, the phosphatidylethanolamine class (PE) was significantly lower in cases at than in controls, and a significant decrease in PE, as well as a change in 20 lipid species from baseline to follow-up in cases was seen. The protein profile did not differ between cases and controls either at baseline or follow-up, or between repeated measurements in cases. Conclusions The observed alterations in the surfactant phospholipids in the RTLF indicate that surfactant homeostasis is affected already in mild to moderate COVID-19, and these changes appear to persist over time.

Daratumumab for High-Risk Smoldering Multiple Myeloma

Passive electroculture using copper rods does not improve yield in home container vegetable gardening

Electroculture, or the practice of applying electric fields or current to plants, has been explored for nearly three hundred years. Recently, home gardeners on social media have adopted the term electroculture to describe inserting copper-wrapped dowels into root soil as a cost-effective means of improving crop yield in small garden spaces. Given the renewed interest, big box stores have begun stocking copper-wrapped dowels as a means of improving plant growth in urban container gardens, yet whether such passive electroculture is sufficiently beneficial to plant growth to justify the cost and materials, particularly of copper, remains debated. It is likely that copper rods produce too little voltage to affect plant physiology. In this study, we tested the hypotheses that 1) inserting copper-wrapped dowel rods into the soil will not improve plant growth, photosynthesis, or yield, and 2) if copper-wrapped dowel rods improve plant growth, it is due to copper fertilization rather than electrical conductance. We tested these hypotheses on two leafy green vegetables, mustard greens and kale, and two root vegetables, beets and turnips, to determine if plant life history was an important factor in the efficacy of passive electroculture. We found no consistent evidence that passive electroculture is beneficial to crop growth or yield in container gardens. Although we documented statistically significant effects of buried copper on the above- and belowground biomass of turnips, it is unlikely that improved turnip yield was due to copper fertilization because plants grown with exposed copper rods did not show the same effect. While crop production could potentially be enhanced by the application of active electrical fields, the voltages required exceed what is produced by copper-wrapped wooden dowels. We therefore suggest that both the production and purchase of such products would waste both financial and natural resources.

Gasping for Strength

Association between albumin infusion and sepsis risk of patients with acute pancreatitis

Objective To investigate whether early administration of serum albumin infusion in the acute pancreatitis (AP) patients admitted to the intensive care unit (ICU) reduces the risk of sepsis. Methods Data were collected from the Medical Information Mart for Intensive Care III and IV databases for this retrospective cohort study. The primary outcome was the occurrence of sepsis in AP patients. We used univariate and multivariate logistic regression models to evaluate the association between albumin infusion and sepsis risk of AP patients. Additional subgroup analysis by stratification to serum albumin were also performed. Results The study included 779 patients with AP. They were divided into a sepsis group (83 patients) and a non-sepsis group (696 patients) according to whether they developed sepsis, and the prevalence of sepsis was approximately 10.65%. Multivariate logistic regression model indicated that albumin infusion was associated with decreased risk of sepsis in the AP patients [adjusted odds ratio (OR)=0.37, 95% confidence interval (CI)=0.13–0.88]. Subgroup analysis showed a negative association between the albumin infusion and sepsis risk in the AP patients with serum albumin ≤ 3.5g/L (adjusted OR=0.29, 95%CI = 0.08–0.77). Conclusion In this study, we found an association between albumin administration and a lower risk of sepsis in AP patients, which persisted after multivariate adjustment. This suggests that albumin infusion may have unique potential benefits for this population.

Neonatal Fc Receptor — Biology and Therapeutics

Interactions between TTYH2 and APOE facilitate endosomal lipid transfer

Abstract The Tweety homologues (TTYHs) constitute a family of eukaryotic membrane proteins that, on the basis of structural features, were recently proposed to contribute to lipid transfer between soluble carriers and cellular membranes1. However, in the absence of supporting data, this function was hypothetical. Here through pull-down of endogenous proteins, we identify APOE as the interaction partner of human TTYH2. Subcellular fractionation and immunocytochemistry assays showed that both proteins colocalize in endosomal compartments. Characterization of the specific interaction between APOE and TTYH2 through binding assays and structural studies enabled us to identify an epitope in an extended domain of TTYH2 that faces the endosomal lumen. Structures of complexes with APOE-containing lipoprotein particles revealed a binding mode that places lipids in a suitable position to facilitate their diffusion into the membrane. Moreover, in vitro studies revealed that lipid transfer is accelerated by TTYH2. Collectively, our findings indicate that TTYH2 has a role in the unloading of APOE-containing lipoproteins after they are endocytosed. These results define a new protein class that facilitates the extraction of lipids from and their insertion into cellular membranes. Although ubiquitous, this process could be of particular relevance in the brain, where APOE is involved in the transfer of lipids between astrocytes and neurons.

Metacontrast masking of symmetric stimuli

This study investigated whether symmetry perception is vulnerable to metacontrast masking and whether such masking selectively disrupts feedback-dependent visual processes. Across four experiments, we employed a metacontrast paradigm with briefly presented targets (20 ms) followed by masks at varying stimulus onset asynchronies (SOAs), manipulating both target–mask configuration and task demands. All experiments produced the classic U-shaped accuracy-by-SOA curve associated with Type B masking, where performance is lowest at intermediate SOAs. Critically, performance at 0 ms SOA varied depending on the perceptual compatibility of the stimuli. In Experiments 1 and 2, the target and mask were spatially complementary and could be perceptually grouped into a unified figure. Under these conditions, performance at 0 ms SOA exceeded the no-mask baseline, reflecting facilitation due to perceptual integration. In contrast, in Experiments 3 and 4—where the stimuli and mask had no complementary shape and could not be integrated into a coherent object—performance at 0 ms SOA was slightly suppressed, indicating that integration failed to occur. These findings suggest that facilitation at short SOAs depends on the rapid formation of a coherent perceptual object, whereas symmetry detection—requiring temporally extended, feedback-supported integration—is more susceptible to early interruption by masking. Together, these results support both dual-channel and recurrent models of visual masking. Type B suppression reflects interactions between fast feedforward and slower feedback signals, while the presence or absence of early facilitation serves as an index of perceptual organization. These findings underscore how stimulus structure and task context affect the temporal dynamics of shape perception.

Restoring the Infant Mortality Rate as a Measure of Societal Health and Well-Being

Characterization of depth perception information inferred from neuronal activity in primary visual cortex

Depth perception is crucial for spatial awareness, enabling animals to interpret three-dimensional environments. Although the primary visual cortex (V1) is known to process depth information, the specific contributions of V1 neurons to various aspects of depth perception remain underexplored. In this study, we investigated how V1 neurons engage in both passive and active depth-related tasks, examining whether distinct neuronal populations support different aspects of depth processing. Using in vivo calcium imaging in freely moving mice, we observed that specific groups of V1 neurons are selectively active in passive (visual cliff) and active (depth discrimination) tasks, suggesting functional segregation within V1. Additionally, neurons in the primary visual cortex prefer encoding objective positions rather than egocentric distances in non-depth-based tasks. Moreover, egocentric distance discrimination, as reflected by the primary visual cortex, appears to be more prospective. These findings provide insight into V1’s versatility, highlighting its potential role in spatial navigation and decision-making.

Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer

Inconclusive proof of ferroelectricity in peptide-VDF ribbons

Mental health-related, existential, and biological factors are associated with the desire to hasten death in Mexican cancer patients undergoing palliative care: A single-center study

Introduction The wish to hasten death (WTHD) is a clinically significant phenomenon that arises from complex suffering. It has been predominantly studied in Caucasian populations, emphasizing the importance of gaining more diverse cultural perspectives. This study explores the factors associated with the WTHD in Mexican cancer patients receiving palliative care from one academic center, with a specific focus on its connection to dignity.“. Patients and methods The study, a cross-sectional research conducted between October 12, 2023, and August 30, 2024, involved patients with confirmed cancer diagnoses who were attending a palliative care service. Patients had applied the Patient Dignity Inventory (PDI), Schedule of Attitudes Toward Hastened Death (SAHD), Brief Edinburgh Depression Scale (BEDS), EORTC QLQ-C15-PAL to assess health-related quality of life, Karnofsky Performance Status Scale (KPSS) to assess functional capacity, and the Edmonton Symptom Assessment System. A PDI score ≥55 indicated a fractured sense of dignity (DPD), while a SAHD score ≥1 indicated the WTHD. Factors associated with the WTHD were identified using multiple logistic regression analysis. The study was approved by the IRB. Results The study included 302 primarily middle-aged (54.5 [45–64]) females (225 [74.5%]), with 9 years of education. They reported high severity of well-being (7 [1–7]) and tiredness (3 [0–6]). Their median KPSS score showed independence (80 [70–80]), despite impacts across all EORTC QLQ-C15-PAL dimensions. DPD was noted in 110 patients (36.5%). The most frequent diagnoses were breast cancer (114 [38%]), lung cancer (33 [11%]), and gastrointestinal cancer (28 [9%]). The WTHD was found in 94 patients (31.1%). Factors significantly associated included tiredness score (OR: 1.147, 95% CI: 1.044–1.261, p = 0.004), BEDS score (1.181, 1.085–1.284, p ≤ 0.001) and a DPD (1.979, 1.038–3.772, p = 0.04). Conclusions The WTHD was found in one out of every three Mexican cancer patients receiving palliative care and was linked to biological-, mental health-, and existential-related factors.