Browse Articles

Interactive 3D segmentation for primary gross tumor volume in oropharyngeal cancer

Abstract Radiotherapy is the main treatment modality of oropharyngeal cancer (OPC), in which an accurate segmentation of primary gross tumor volume (GTVt) is essential but also challenging due to significant interobserver variability and the time consumed in manual tumor delineation. For such a challenge an interactive deep learning (DL) based approach offers the advantage of automatic high-performance segmentation with the flexibility for user correction when necessary. In this study, we investigate an interactive DL for GTVt segmentation in OPC by introducing a novel two-stage Interactive Click Refinement (2S-ICR) framework and implementing state-of-the-art algorithms. Using the 2021 HEad and neCK TumOR dataset for development and an external dataset from The University of Texas MD Anderson Cancer Center for evaluation, the 2S-ICR framework achieves a Dice similarity coefficient of 0.722 ± 0.142 without user interaction and 0.858 ± 0.050 after ten interactions, thus outperforming existing methods in both cases.

Daily briefing: This marsupial is biofluorescent — the month’s best science images

Progressive damage mechanism of rock-anchoring interface under cyclic impact loading

Bearing fault diagnosis based on improved DenseNet for chemical equipment

Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924

Abstract A growing body of knowledge implicates perturbed RNA homeostasis in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that currently has no cure and few available treatments. Dysregulation of the multifunctional RNA-binding protein TDP-43 is increasingly regarded as a convergent feature of this disease, evidenced at the neuropathological level by the detection of TDP-43 pathology in most patient tissues, and at the genetic level by the identification of disease-associated mutations in its coding gene TARDBP . To characterize the transcriptional landscape induced by TARDBP mutations, we performed whole-transcriptome profiling of motor neurons (MNs) differentiated from two knock-in iPSC lines expressing the ALS-linked TDP-43 variants p.A382T or p.G348C. Our results show that the TARDBP mutations significantly altered the expression profiles of mRNAs and microRNAs of the 14q32 cluster in MNs. Using mutation-induced gene signatures and the Connectivity Map database, we identified compounds predicted to restore gene expression toward wild-type levels. Among top-scoring compounds selected for further investigation, the NEDD8-activating enzyme inhibitor MLN4924 effectively improved cell viability and neuronal activity, highlighting a possible role for protein post-translational modification via NEDDylation in the pathobiology of TDP-43 in ALS.

CATT haplotype of the FKBP5 gene and dissociative phenomenology

Abstract Survival mechanisms are evolutionary grown behaviors in life-threatening situations. They are thought to be determined by genetic patterns involved in stress systems, such as the control of the hypothalamic-pituitary-adrenal (HPA) axis. FK506 binding protein 5 (FKBP5) is a co-chaperone that is involved in modulating glucocorticoid receptor (GR) sensitivity in response to stress. Dissociation is thought to be one of these survival strategies and appears to be associated with common haplotypes of the FKBP5 gene formed by four single nucleotide polymorphisms (SNPs) (rs9296158, rs3800373, rs1360780, and rs9470080). The aim of the study was to examine the association between the FKBP5 haplotypes, type of childhood trauma and different types of dissociative phenomena. Dissociation encompasses a wide range of different phenomena. A common categorization has been made that distinguishes between ‘detachment’ and ‘compartmentalisation’ dissociation. Therefore, both categories were included in the study, including identity dissociation as the most severe form of compartmentalisation dissociation. We analyzed the association between six different types of dissociative phenomena, different types of childhood trauma and the FKBP5 haplotypes in 194 participants, primarily Black Americans of low socioeconomic status and high trauma burden, who participated in the Grady Trauma Project in Atlanta. We found that only identity dissociation was significantly associated with the CATT FKBP5 haplotype, regardless of the type of childhood trauma. In particular, individuals with one or two CATT haplotypes are 15 times more likely to develop identity dissociation than others. In conclusion, our findings indicate a link between gene variants involved in the regulation of stress systems and self-development under conditions of traumatic stress during the developmental period, which may be important for the study of disorders such as complex post-traumatic stress disorder.

Does ResearchGate have a growing credibility problem?

Single port laparoscopic umbilical fold reinforcement surgery reduces the postoperative recurrence rate of pediatric giant inguinal hernia

Development of a hip osteoarthritis index for gait quality assessment: a data-driven comparative study

Adaptive control strategies for button motor actuated insect scale flapping wing MAV mechanisms

Abstract The development of Flapping Wing Micro Aerial Vehicles (FWMAVs) has gained significant attention due to their potential for energy-efficient, lightweight, and highly maneuverable flight inspired by nature. This study presents innovative designs and adaptive control strategies for insect-scale FWMAVs, utilizing compact button vibrator motors as actuators for wing flapping. These actuators offer advantages in size, weight, and power efficiency but pose challenges in achieving continuous and controlled motion due to mechanical, control, and durability constraints. The research explores multiple lever alignment configurations using simplified crank-slider mechanisms, driven by single and dual coreless DC motors powered by a 1–3.7 V DC supply. Detailed modeling in SIMSCAPE Multibody and structural movement analysis using Compmech GIM software facilitate the evaluation of variations in flapping frequency, velocity, and acceleration. Advanced control strategies, including Self-Regulatory Fractional Fuzzy Control (SRFFC) and Fractional PID (FPID), are assessed under simulated and real-world conditions to mitigate external disturbances. Additionally, an AI-based disturbance observer is implemented to enhance stability and optimize power efficiency by compensating for environmental disturbances. Performance metrics such as rise time, settling time, overshoot, and integral absolute error (IAE) demonstrate the superior efficiency and disturbance rejection capabilities of SRFFC compared to FPID. Experimental validation and real-time assessments of maneuvering capabilities, including leftward, rightward, and forward movements, further substantiate the proposed strategies. This study underscores the potential of SRFFC-driven designs and modular motor configurations to enhance the performance, control, and applicability of FWMAVs for advanced micro-aerial systems.

Ultradian rhythms of CRH ^PVN neuron activity, behavior, and stress hormone secretion

The stress axis is always active, even in the absence of any threat. This manifests as hourly pulses of corticosteroid stress hormone secretion over the day. Corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (CRH PVN ) control both the neuroendocrine stress axis as well as stress-associated behaviors. However, it is currently unclear how the resting activity of these neurons is coordinated with both spontaneous behavior and ultradian pulses of corticosteroid secretion. To investigate this, we performed fiber photometry recordings of CRH PVN neuron activity in Crh-Ires-Cre mice and a newly generated line of Crh-Ires-Cre rats. In both mice and rats, CRH PVN neurons displayed an ultradian rhythm of activity with reoccurring upstates of activity approximately once per hour over the 24-h day. Upstates in activity were coordinated with increases in animal activity/arousal. Chemogenetic activation of CRH PVN neurons was also sufficient to induce behavioral arousal. In rats, increases in CRH neural activity preceded some pulses of corticosteroid secretion but not others. Thus, while CRH PVN neurons display an ultradian rhythm of activity over the 24-h day that is coordinated with behavioral arousal, the relationship between CRH PVN activity and pulses of corticosteroid secretion is not one-to-one.

Absence of phonon softening across a charge density wave transition due to quantum fluctuations

Kagome metals have emerged as a frontier in condensed matter physics due to their potential to host exotic quantum states. Among these, CsV 3 Sb 5 has attracted significant attention for the unusual coexistence of charge density wave (CDW) order and unconventional superconductivity, presenting an ideal system for exploring the emergent phenomena from the interplay of phonons, electronic fluctuations, and topological effects. The nature of CDW formation in CsV 3 Sb 5 is unconventional and has sparked considerable debate. In this study, we examine the origin of the CDW state via ab initio finite-temperature simulations of the lattice dynamics. Through a comparative study of CsV 3 Sb 5 and 2H-NbSe 2 , we demonstrate that the experimental absence of phonon softening—a hallmark of conventional CDW transition—in CsV 3 Sb 5 along with the presence of a weakly first-order transition, can be attributed to quantum zero-point atomic motion. This zero-point motion smears the free energy landscape of CDW, effectively stabilizing the pristine structure even below the CDW transition temperature. We argue that this surprising behavior could cause coexistence of pristine and CDW structures across the transition and lead to a weak first-order transition. Our predicted lattice dynamical behavior is supported by coherent phonon spectroscopy in single-crystalline CsV 3 Sb 5 . Our results provide crucial insights into the formation mechanism of CDW materials that exhibit little to no phonon softening, including cuprates, and highlight the surprising role of quantum effects in emergent properties of relatively heavy-element materials like CsV 3 Sb 5 .

Revisiting the Eoarchean Akilia quartz-pyroxene rock with potassium isotopes: Implications for early-ocean sedimentation

The Eoarchean quartz-pyroxene rock from Akilia Island in Greenland has been proposed as one of Earth’s oldest banded iron formations (BIF) and a potential host for the earliest biosignatures. However, the origin of its protolith, whether it metamorphosed from an igneous or sedimentary precursor, remains debated. Here, we revisit this longstanding Akilia controversy using potassium isotope analyses, comparing Akilia samples with BIFs and black shales spanning the Eoarchean to Mesoproterozoic. Our results demonstrate that BIFs and black shales show systematic potassium isotope variations correlated with their potassium contents. Potassium-poor BIF layers display heavier isotopic compositions close to seawater values, whereas clay-rich layers exhibit elevated potassium contents and lighter isotopic signatures. The Akilia quartz-pyroxene rock was initially characterized by low potassium concentrations and heavy potassium isotopic compositions consistent with chemical sediments deposited from ancient seawater. It was subsequently modified by metasomatic fluids derived from nearby metamorphosed igneous rocks. These findings support a sedimentary origin for the Akilia quartz-pyroxene rock. Furthermore, our study provides an isotopic framework for interpreting ancient oceanic environments and offers insights into the potassium cycling and habitability of early Earth.

Casimir self-assembly: A platform for measuring nanoscale surface interactions in liquids

Self-assembly (SA) plays a pivotal role in nanotechnology, offering cost-effective methods for bottom–up fabrication and providing versatile model systems for investigating fundamental interactions in various bioinspired systems. However, current methods for investigating and quantifying the dynamics of SA systems are limited in their applicability to planar interfaces, particularly in liquid environments. These methods typically rely on analyzing the collective behavior of particle suspensions rather than directly probing the specific interactions between individual particles. Here, we introduce Casimir self-assembly (CaSA) as a platform, integrating colloidal science, nanophotonics, and fluctuational electrodynamics to study long-range interactions and stability in planar SA systems. Using thermal fluctuations as a probe and visible-range Fabry–Pérot resonances as an optical readout, we demonstrate that CaSA enables a direct in situ study of the Casimir–Lifshitz electrostatic interaction. This approach allows us to map stability regimes of colloidal materials by varying ionic strength and identifying conditions for stable assembly and aggregation limits, and moreover is used to measure the surface charge density of an individual colloidal object down to fractions of an electron charge per square nanometer. Our platform overcomes the limitations of current methods, providing an experimental tool for exploring SA dynamics in situ and expanding the understanding of suspension stability in liquids at the single-particle level. With potential for future applications, CaSA is scalable for studying interfacial forces and is adaptable to multivalent electrolytes and biosensing.

A bacteria-based search for drugs against avian and swine flu yields a potent and resistance-resilient channel blocker

Influenza represents a significant threat with seasonal epidemics that can transition to global pandemics, and cross-species infection presenting a continuous challenge. While vaccines and several antiviral drugs are available, constant genetic changes vitiate these prevention and treatment options. Consequently, we decided to search for inhibitors against one of the virus’s validated drug targets, its M2 channel that is blocked by aminoadamantanes. Regrettably, widespread mutations in M2 abolish the antiflu activity of said blockers. Therefore, we devised bacteria-based genetic assays that can screen for drugs against aminoadamantane-sensitive and resistant M2 channels and map the resistance potential of any identifiable blocker. Subsequent in cellulo testing and structure–activity relationship studies yielded a synergistic combination of two compounds, Theobromine and Arainosine, that exhibited remarkable antiviral activity by directly inhibiting the virus’s channel. The drug duo was potent against H1N1 pandemic swine flu, H5N1 pandemic avian flu, and aminoadamantane-resistant and sensitive strains alike, exhibiting activity that surpassed oseltamivir, the leading antiflu drug on the market. When this drug duo was tested in an animal model, it once more outperformed oseltamivir, considerably reducing disease symptoms and viral RNA progeny. Importantly, harnessing the bacterial genetic selection, we could demonstrate that the drug duo’s potential for eliciting drug resistance is significantly smaller and molecularly distinct from that of aminoadamantanes. In conclusion, the outcome of this study represents a new potential treatment option for influenza alongside an approach that is sufficiently general and readily applicable to other viral targets.

A minimal model of panimmunity maintenance by horizontal gene transfer in the ecological dynamics of bacteria and phages

Bacteria and phages have been in an ongoing arms race for billions of years. To resist phages bacteria have evolved numerous defense systems, which nevertheless are still overcome by counterdefense mechanisms of specific phages. These defense/counterdefense systems are a major element of microbial genetic diversity and have been demonstrated to propagate between strains by horizontal gene transfer (HGT). It has been proposed that the totality of defense systems found in microbial communities collectively form a distributed “pan-immune” system with individual elements moving between strains via ubiquitous HGT. Here, we formulate a Lotka–Volterra type model of a bacteria/phage community interacting via a combinatorial variety of defense/counterdefense systems and show that HGT enables stable maintenance of diverse defense/counterdefense genes in the microbial pan-genome even when individual microbial strains inevitably undergo extinction. This stability requires the HGT rate to be sufficiently high to ensure that some descendant of a “dying” strain survives, thanks to the immunity acquired through HGT from the community at large, thus establishing a new strain. This mechanism of persistence for the pan-immune gene pool is fundamentally similar to the “island migration” model of ecological diversity, with genes moving between genomes instead of species migrating between islands.

Orexin effect on physiological pulsations of the human brain

Sleep promotes cerebrospinal fluid (CSF) to interstitial fluid (ISF) exchange in the brain facilitated by brain pulsations. Especially brain vasomotion and arterial pulsations modulated by noradrenaline drive the intracranial fluid dynamics. Narcolepsy type 1 (NT1) entails lessened orexinergic output to wake-promoting systems including the noradrenergic locus coeruleus. As arousal state and noradrenergic signaling affect CSF-ISF clearance, we chose patients with NT1 as a human orexin-targeted model of sleep-related pathology bridging the gap between healthy awake and sleep with respect to CSF flow pulsations. We also investigated the sensitivity of magnetic resonance encephalography to detect flow with a phantom model and sought to replicate earlier pulsation findings in sleep. In this case–control study, we used fast functional MRI to map brain pulsations in groups of healthy sleeping controls (n = 13), healthy awake controls (n = 79), and awake NT1 (n = 21) patients. We measured the very low frequency (0.008 to 0.1) and cardiorespiratory frequencies and calculated in each frequency band the coefficient of variation, spectral power, and full band spectral entropy to obtain brain pulsation maps. We uncovered a brain pulsation profile from healthy waking to sleep to a sleep-related pathology NT1 prominently affected in the vascular-related vasomotor and brain arterial pulsations. Our results established how drivers of brain hydrodynamics are affected by a specific loss of key neurotransmitter governing arousal compared to healthy sleep. We also showed with a phantom model that MREG is sensitive to flow-related signal changes and solidified evidence of brain pulsations in the healthy states of sleep and wakefulness.

SCoTCH-seq reveals that 5-hydroxymethylcytosine encodes regulatory information across DNA strands

In mammalian genomes, cytosine modifications form a layer of regulatory information alongside the genetic code. Decoding this information is crucial to our understanding of biology and disease. Established sequencing methods cannot simultaneously resolve cytosine’s three most common forms—cytosine (C), 5-methylcytosine (mC), and 5-hydroxymethylcytosine (hmC)—across both strands of the DNA double helix. Thus, how epigenetic information is distributed in DNA remains unclear. Here, we present S trand- Co upled T andem C ytosine H ydroxymethylation and methylation sequencing (SCoTCH-seq): an accurate and quantitative, base-resolution approach to sequence genomes, together with mC and hmC, in both strands of the same DNA fragment. We show that different forms of cytosine combine across the double helix at CpG sites to form discrete information states in the mouse epigenome. These CpG states have distinct genomic distributions—including at promoters, enhancers, and gene bodies—and have different relationships with transcription. We show that while all possible forms of hydroxymethylation occur, hmC is predominantly asymmetric and that different forms of asymmetric hmC are not equivalent. Our findings demonstrate that 5-hydroxymethylcytosine combines with different cytosine variants across the DNA double helix to form distinct states of regulatory information.

Foraging ants as liquid brains: Movement heterogeneity shapes collective efficiency

Liquid brains conceptualize living systems that operate without central control, where collective outcomes emerge from local and dynamic interactions. This concept extends beyond ants and other social insects to include immune systems, slime molds, and microbiomes. In such systems, connectivity scales with population density, facilitating more efficient information transfer as group size increases. However, in sparse conditions, where fewer individuals interact, movement likely plays a crucial role in shaping connectivity, ensuring optimal collective efficiency. We tested this hypothesis during the foraging process of Aphaenogaster senilis , an ant species that does not primarily rely on chemical communication. We empirically measured ant movement behavior and characterized their foraging dynamics across large spatiotemporal scales, closely reflecting the species’ natural ecology. Integrating observed movement heterogeneity into a neuronal-like model, we quantitatively replicated ants foraging efficiency and spatiotemporal dynamics. Our results reveal that a simple feedback mechanism, mediated by local interactions, governs the foraging patterns of A. senilis . Such feedback is modulated by adjusting the proportion of two coexisting movement behaviors: recruits, which facilitated information transfer and food exploitation by aggregating closely to the nest and the food patches, and scouts, which could bypass this feedback and discover alternative food sources. Therefore, distinct movement patterns contributed differently to optimizing each phase of the foraging process, proving an adaptive mechanism to balance exploration and exploitation. Our findings underscore how incorporating specific biologically grounded insights into complex systems frameworks, enhances our understanding of the mechanisms underlying collective intelligence in biological systems.

In situ cryo-ET visualization of mitochondrial depolarization and mitophagic engulfment

Defective mitochondrial quality control in response to loss of mitochondrial membrane polarization is implicated in Parkinson’s disease by mutations in PINK1 and PRKN . Parkin-expressing U2 osteosarcoma (U2OS) cells were treated with the depolarizing agents oligomycin and antimycin A (OA) and subjected to cryo-focused ion beam milling and in situ cryo-electron tomography. Mitochondria were fragmented and devoid of matrix calcium phosphate crystals. Phagophores were visualized, with bridge-like lipid transporter densities connected to mitophagic phagophores. A subpopulation of ATP synthases relocalized from cristae to the inner boundary membrane. The structure of the dome-shaped prohibitin complex, a dodecamer of PHB1-PHB2 dimers, was determined in situ by subtomogram averaging in untreated and treated cells and found to exist in open and closed conformations, with the closed conformation being enriched by OA treatment. These findings provide a set of native snapshots of the manifold nano-structural consequences of mitochondrial depolarization and provide a baseline for future in situ dissection of Parkin-dependent mitophagy.