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Single-molecule localization microscopy enables high-resolution imaging of molecular interactions, but discriminating molecular binding types has traditionally relied on complex strategies, such as multiple dyes, time-division techniques, or kinetic analysis, that are asynchronous, invasive, or time-consuming. Here, we uncover previously overlooked spatiotemporal information embedded within diffraction-limited fluorescence, enabling synchronous classification of individual binding event videos using only a single fluorescent dye. Building on this insight, we propose a Temporal-to-Context Convolutional Neural Network (T2C CNN), which integrates long-term spatial convolutions, shallow cross-connected blocks, and a pooling-free structure to enhance contextual representation while preserving fine-grained temporal features. Applied to DNA-PAINT experiments, T2C CNN achieves up to 94.76% classification accuracy and outperforms state-of-the-art video classification models by 15-25 percentage points. Our approach enables rapid and precise binding-type recognition from fluorescence video data, reducing observation time from minutes to seconds and facilitating high-throughput single-molecule imaging without requiring multiple dye channels or extended kinetic measurements. Yin and colleagues propose that diffraction-limited fluorescence videos contain hidden binding-type information. The authors present a deep learning model, T2C CNN, which exploits that hidden information to classify molecular interactions with high accuracy using a single dye in seconds.

Dengue virus serotype 2 (DENV2) alone undergoes structural expansion at 37 °C (associated with host entry), despite high sequence and structural homology among the four known serotypes. The basis for this differential expansion across strains and serotypes is unknown and necessitates mapping of the dynamics of dengue whole viral particles to describe their coordinated motions and conformational changes when exposed to host-like environments. Here we capture the dynamics of intact viral particles of two serotypes, DENV1 and DENV2, by amide hydrogen/deuterium exchange mass spectrometry (HDXMS) and time resolved Förster Resonance Energy Transfer. Our results show temperature-dependent dynamics hotspots on DENV2 and DENV1 particles with DENV1 showing expansion at 40 °C but not at 37 °C. HDXMS measurement of virion dynamics in solution offers a powerful approach to identify potential epitopes, map virus-antibody complex structure and dynamics, and test effects of multiple host-specific perturbations on viruses and virus-antibody complexes. Temperature differences between mosquitoes and humans trigger structural changes in dengue virus 2 (DENV2) particles, but not in other DENV serotypes. Here, using HDXMS, the authors describe serotype-specific expansion of intact viral particles of DENV1 and DENV2 at 28 °C (mosquitoes), 37 °C (humans) and 40 °C (fever).

Electroencephalography (EEG) provides a non-invasive means to advancing our understanding of the development and function of the brain. However, majority of the world’s population residing in low and middle income countries has historically been limited from contributing to, and thereby benefiting from, such neurophysiological research, due to lack of scalable validated methods of EEG data collection. In this study, we establish a standard operating protocol to collect eyes-open and eyes-closed resting-state EEG data using a low-cost portable EEG device in rural households through formative work in the community. We then evaluate the acceptability of these EEG assessments to young children and feasibility of administering them through non-specialist workers. Finally, we describe properties of the EEG recordings obtained using this novel approach to EEG data collection. The formative phase was conducted with 9 families which informed protocols for consenting, child engagement strategies and data collection. The protocol was then implemented on 1265 families. 977 children and 1199 adults provided resting-state data for this study. 259 children refused to wear the EEG cap or removed it, and 58 children refused the eyes-closed recording session. Hardware or software issues were experienced during 30 and 25 recordings in eyes-open and eyes-closed conditions respectively. Disturbances during the recording sessions were rare and included participants moving their heads, touching the EEG headset with their hands, opening their eyes within the eyes-closed recording session, and presence of loud noises in the testing environment. Similar to findings in laboratory-based studies from high-income settings, the percentage of recordings which showed an alpha peak was higher in eyes-closed than eyes-open condition, and the mean position of the alpha peak was found to be lower in children (8.43 Hz, SD=1.73) as compared to adults (10.71 Hz, SD=3.96). We observed a deterioration in the EEG signal with prolonged device usage. This study demonstrates the acceptability, feasibility and utility of conducting EEG research at scale in a rural low-resource community, while highlighting its potential limitations, and offers the impetus needed to further refine the methods and devices and validate such scalable methods to overcome existing research inequity.

The Mundwara alkaline plutonic complex (Rajasthan, north-western India) is considered a part of the Late Cretaceous–Palaeogene Deccan Traps flood basalt province, based on geochronological data (mainly 40 Ar/ 39 Ar, on whole rocks, biotite and hornblende). We have studied the petrology and mineral chemistry of some Mundwara mafic rocks containing mica and amphibole. Geothermobarometry indicates emplacement of the complex at middle to upper crustal levels. We have obtained new 40 Ar/ 39 Ar ages of 80–84 Ma on biotite separates from mafic rocks and 102–110 Ma on whole-rock nepheline syenites. There is no evidence for excess 40 Ar. The combined results show that some of the constituent intrusions of the Mundwara complex are of Deccan age, but others are older and unrelated to the Deccan Traps. The Mundwara alkaline complex is thus polychronous and similar to many alkaline complexes around the world that show recurrent magmatism, sometimes over hundreds of millions of years. The primary biotite and amphibole in Mundwara mafic rocks indicate hydrous parental magmas, derived from hydrated mantle peridotite at relatively low temperatures, thus ruling out a mantle plume. This hydration and metasomatism of the Rajasthan lithospheric mantle may have occurred during Jurassic subduction under Gondwanaland, or Precambrian subduction events. Low-degree decompression melting of this old, enriched lithospheric mantle, due to periodic diffuse lithospheric extension, gradually built the Mundwara complex from the Early Cretaceous to Palaeogene time.

Smartphones have become integral to people's lives, with a noticeable increase in the average screen time, both on a global scale and, notably, in India. Existing research links mobile consumption to sleep problems, poor physical and mental health, and lower subjective well-being. The comparative effectiveness of monetary incentives given for self-selected versus assigned targets on reducing screen time and thereby improving mental health remains unanswered. This study aims to assess the impact of monetary incentives and target selection on mobile screen time reduction and mental health. We designed a 3-armed randomized controlled trial conducted with employees and students at an educational institution in India. The study is conducted digitally over 12 weeks, including baseline (2 weeks), randomization (1 week), intervention (5 weeks), and postintervention (4 week) periods. We emailed the employees and students to inquire about their interest in participation. Those who expressed interest received detailed study information and consent forms. After securing consent, participants were asked to complete the initial survey and provide their mobile screen time during the baseline period. At the beginning of the intervention period, the participants were randomly allocated into 1 of 3 study groups in a 2:2:1 ratio (self-selected vs assigned vs control). Participants in the self-selected group were presented with 3 target options: 10%, 20%, and 30%, and they were asked to self-select a target to reduce their mobile screen time from their baseline average mobile screen time. Participants in the assigned group were given a target to reduce their mobile screen time from their baseline average mobile screen time. The assigned target was set as the average of the targets selected by participants in the self-selected group. During the intervention period, participants in the self-selected and assigned group were eligible to receive a monetary incentive of INR (Indian Rupee) 50 (US $0.61) per day for successfully attaining their target. Participants in the control group neither received nor selected a target for reducing their mobile screen time and did not receive any monetary incentives during the intervention period. All participants received information regarding the advantages of reducing mobile screen time. As an incentive, all participants would receive INR 500 (US $6.06) upon completion of the study and a chance to win 1 of 2 lotteries valued at INR 5000 (US $60.55) for consistently sharing their mobile screen time data. Currently, the study intervention is being rolled out. Enrollment occurred between August 21, 2023, and September 2, 2023; data collection concluded in November 2023. We expect that results will be available by early 2024. The monetary incentives and self-selected versus assigned targets might be effective interventions in reducing mobile screen time among working professionals and students. AsPredicted 142497; https://aspredicted.org/hr3nn.pdf. DERR1-10.2196/53756.

The Human Immunodeficiency Virus-1 (HIV-1) nucleocapsid protein (NC) as a mature protein or as a domain of the Gag precursor plays important roles in the early and late phases of the infection. To better understand its roles, we searched for new cellular partners and identified the RNA-binding protein Unr/CSDE1, Upstream of N-ras, whose interaction with Gag and NCp7 was confirmed by co-immunoprecipitation and FRET-FLIM. Unr interaction with Gag was found to be RNA-dependent and mediated by its NC domain. Using a dual luciferase assay, Unr was shown to act as an ITAF (IRES trans-acting factor), increasing the HIV-1 IRES-dependent translation. Point mutations of the HIV-1 IRES in a consensus Unr binding motif were found to alter both the IRES activity and its activation by Unr, suggesting a strong dependence of the IRES on Unr. Interestingly, Unr stimulatory effect is counteracted by NCp7, while Gag increases the Unr-promoted IRES activity, suggesting a differential Unr effect on the early and late phases of viral infection. Finally, knockdown of Unr in HeLa cells leads to a decrease in infection by a non-replicative lentivector, proving its functional implication in the early phase of viral infection.

Background Postpartum depression (PPD) negatively affects maternal well-being and early child development (ECD). While research often focuses on the early postpartum depression, symptoms can emerge or persist later in the first year, potentially affecting mothers and children differently at this stage. Yet, the 12-month postpartum period remains understudied globally, particularly in low-resourced settings where contextual stressors are pronounced. This study addresses the urgent need to understand later-stage postpartum depression and how it influences child development at 18 months, a critical period for identifying early developmental delays. Methods We analysed longitudinal data from a cluster randomised trial of an integrated mother-child intervention in rural India (Haryana). Mother-child dyads enrolled between 18 June 2015 and 1 July 2017 were assessed for PPD at 12 months using Patient Health Questionnaire-9 (PHQ-9) and for child development at 18 months with Bayley Scales of Infant and Toddler Development-III. We examined PPD risk factors using logistic regression and the association between PPD and ECD through multinomial regression models, accounting for covariates and clustering. Results Among 2007 mothers assessed at 12 months, PPD prevalence was 13.1% (PHQ-9 ≥ 5). Maternal adverse events (OR = 1.53, CI: 1.35–1.73, p  < 0.001) and psychosocial stress (OR = 1.10, 95% CI: 1.08–1.12, p  < 0.001) increased PPD odds, while psychosocial support (OR = 0.97, 95% CI: 0.96–0.98, p  < 0.001) and higher socio-economic status (OR = 0.72, 95% CI: 0.64–0.79, p  < 0.001) reduced them. Among 1250 dyads assessed at 18 months, PPD predicted mild-to-moderate (RRR = 1.63, 95% CI: 1.13–2.36, p  < 0.01) and severe (RRR = 1.64, 95% CI: 1.03–2.61, p  < 0.05) language delays, but not cognitive or motor delays. These associations were not significant after adjustment. Conclusions This is among the first Indian studies to longitudinally examine the association between postpartum depression at 12 months and child development at 18 months, addressing a major evidence gap in rural settings. The study identified a distinct risk profile for postpartum depression shaped by socioeconomic and maternal adversity. Postpartum depression showed domain-specific associations with language delays, explained by contextual factors. These findings highlight the need to integrate evidence-based mental health screening and support for at-risk mothers and children into existing maternal and child health services in rural contexts.

IntroductionPresently, there are few population-level strategies to address SARS-CoV-2 infection except preventive measures such as vaccination. Micronutrient deficiency, particularly vitamin D and zinc deficiency, has been associated with dysregulated host responses, and may play an important role in COVID-19.Methods and analysisWe have designed a 2×2 factorial, randomised, double-blind, multi-centre placebo-controlled trial to evaluate the effect of vitamin D and zinc on COVID-19 outcomes in Maharashtra, India. COVID-19 positive individuals are recruited from hospitals in Mumbai and Pune. Participants are provided (1) vitamin D3 bolus (180 000 IU) maintained by daily dose of 2000 IU and/or (2) zinc gluconate (40 mg daily), versus placebo for 8 weeks. Participants undergo a detailed assessment at baseline and at 8 weeks, and are monitored daily in hospital or every 3 days after leaving the hospital to assess symptoms and other clinical measures. A final follow-up telephone call occurs 12 weeks post-enrolment to assess long-term outcomes. The primary outcome of the study is to time to recovery, defined as time to resolution of all of fever, cough and shortness of breath. Secondary outcomes include: duration of hospital stay, all-cause mortality, necessity of assisted ventilation, change in blood biomarker levels and individual symptoms duration. Participant recruitment commenced on April 2021.Ethics and disseminationEthical approval was obtained from institutional ethical committees of all participating institutions. The study findings will be presented in peer-reviewed medical journals.Trial registration numbersNCT04641195, CTRI/2021/04/032593, HMSC (GOI)-2021-0060.

Background: Assessment of cognitive development is essential to identify children with faltering developmental attainment and monitor the impact of interventions. A key barrier to achieving these goals is the lack of standardized, scalable tools to assess cognitive abilities. Objective: This study aimed to develop a tablet-based gamified assessment of cognitive abilities of 3-year-old children which can be administered by non-specialist field workers. Methods: Workshops among domain experts, literature search for established and gamified paradigms of cognitive assessments and rapid review of mobile games for 3-year-old children was done to conceptualize games for this study. Formative household visits (N = 20) informed the design and content of the games. A cross-sectional pilot study (N = 100) was done to assess feasibility of the tool and check if increasing levels of difficulty and the expected variability between children were evident in game metrics. In-depth interviews (N = 9) were conducted with mothers of participating children to assess its acceptability. Results: Six cognitive domains were identified as being integral to learning - divided attention, response inhibition, reasoning, visual form perception and integration and memory. A narrative, musical soundtrack and positive reinforcement were incorporated into the tool to enhance participant engagement. Child performance determined level timers and difficulty levels in each game. Pilot data indicate that children differ in their performance profile on the tool as measured by the number of game levels played and their accuracy and completion time indicating that it might be possible to differentiate children based on these metrics. Qualitative data suggest high levels of acceptability of the tool amongst participants. Conclusions: A DEvelopmental assessment on an E-Platform (DEEP) has been created comprising distinct games woven into a narrative, which assess six cognitive domains, and shows high levels of acceptability and generates metrics which may be used for validation against gold standard cognitive assessments.

Cognitive development in early childhood is critical for life-long well-being. Existing cognitive development surveillance tools require lengthy parental interviews and observations of children. Developmental Assessment on an E-Platform (DEEP) is a digital tool designed to address this gap by providing a gamified, direct assessment of cognition in young children which can be delivered by front-line providers in community settings. This longitudinal study recruited children from the SPRING trial in rural Haryana, India. DEEP was administered at 39 (SD 1; N = 1359), 60 (SD 5; N = 1234) and 95 (SD 4; N = 600) months and scores were derived using item response theory. Criterion validity was examined by correlating DEEP-score with age, Bayley’s Scales of Infant Development (BSID-III) cognitive domain score at age 3 and Raven’s Coloured Progressive Matrices (CPM) at age 8; predictive validity was examined by correlating DEEP-scores at preschool-age with academic performance at age 8 and convergent validity through correlations with height-for-age z-scores (HAZ), socioeconomic status (SES) and early life adversities. DEEP-score correlated strongly with age (r = 0.83, 95% CI 0.82 0.84) and moderately with BSID-III (r = 0.50, 0.39 – 0.60) and CPM (r = 0.37; 0.30 – 0.44). DEEP-score at preschool-age predicted academic outcomes at school-age (0.32; 0.25 – 0.41) and correlated positively with HAZ and SES and negatively with early life adversities. DEEP provides a valid, scalable method for cognitive assessment. It’s integration into developmental surveillance programs could aid in monitoring and early detection of cognitive delays, enabling timely interventions.