bluuebunny/crossref_metadata_2025 huggingface dataset:
Transport-Related Effects on Intrinsic and Synaptic Properties of Human Cortical Neurons: A Comparative Study
Authors: Qi Guanxiao , Yang Danqing , Bak Aniella , Hucko Werner , Delev Daniel , Hamou Hussam , Feldmeyer Dirk , Koch Henner
Published: October 2024

Transporting human brain tissue from the operating theater to an off-site laboratory may affect sample integrity for electrophysiological studies. This study investigated how a 30-40 minute transport influenced the intrinsic, synaptic, and morphological properties of human cortical neurons. Electrophysiological recordings were performed on Layer 2/3 (L2/3 pyramidal cells and fast-spiking (FS) interneurons from human cortical slices (n = 200 neurons from 32 surgeries), comparing on-site recordings at RWTH Aachen University Hospital and off-site at Research Centre Juelich. Action potential firing patterns remained largely preserved across both recording sites, but several differences were observed. Off-site recorded pyramidal cells showed a slightly depolarized resting membrane potential and a significantly lower rheobase current. In off-site recorded FS interneurons, we found a narrower action potential half-width and an increased amplitude, suggesting altered ion channel kinetics and/or neuromodulatory environment. Additionally, a significant reduction in large rhythmic depolarizations (LRDs) and the amplitudes of excitatory postsynaptic potentials (EPSPs) in off-site recorded FS interneurons indicated an impaired synaptic efficacy. The dendritic spine densities in apical oblique and apical tuft dendrites of off-site recorded pyramidal cells were also reduced. These findings emphasize the need for optimized transport conditions to preserve synaptic integrity, network properties, and neuronal morphology. Standardized protocols are crucial for ensuring reliable and reproducible results in studies of human cortical microcircuits.

Significance Statement

This study demonstrates that transporting live human brain tissue for neuronal recordings significantly impacts the intrinsic, synaptic, and network properties of cortical neurons. By comparing on-site and off-site recordings, we found that even a brief transportation (30-40 minutes) induces increased neuronal excitability, reduced synaptic efficacy, and diminished network events such as LRDs. These alterations are likely due to the mechanical stress and washout of critical neuromodulators, which compromise tissue integrity and neuronal function. The findings underscore the necessity for optimizing transport protocols to preserve synaptic and network integrity, ensuring reliable and reproducible results in human brain research. Ultimately, this work advances our understanding of cortical microcircuitry and informs best practices for handling human brain tissue in experimental settings.
A mammalian inferior colliculus model for sound source separation using interaural time differences
Authors: Leibold Christian , Groß Sebastian
Published: October 2024

The inferior colliculus (IC) hosts many neurons tuned to interaural time differences (ITDs) at low frequencies. ITD tuning, however, is already observed and generated in the superior olivary complex. Here, we argue that combining ITD sensitive inputs from medial superior olive (MSO) and low-frequency lateral superior olive (LSO) requires a temporally well adjusted delay of commissural fibers from LSO to IC, given the fast synaptic kinetics of IC neurons. We present a normative model of the midbrain auditory circuitry that finds an optimal commissural delay of 0.3 cycles and optimal synaptic strengths by maximizing the firing rate of IC neurons for a given ITD. The model suggests that, by varying the relative synaptic weight of MSO and LSO input, individual neurons are optimized to transmit information for any sound source in complex auditory scenes. ITD tuning of IC neurons results as a side effect and follows the statistics known from experimental recordings.
Distinct representations of economic variables across regions and projections of the frontal cortex
Authors: Majumdar Antara , Ashcroft Caitlin , Fritsche Matthias , Zatka-Haas Peter , Walker Niamh , Bijoch Lukasz , Mistry Leah , Rominto Anita M. , Duckworth-Essilfie Tolu , Swann Jake , Molnar Zoltan , Packer Adam M. , Butt Simon J. B. , Lak Armin
Published: October 2024

Economic decision-making requires evaluating information about available options, such as their expected value and economic risk. Previous studies have shown that frontal cortical neurons encode these variables, but how this encoding is structured across different frontal regions and projection pathways remains unclear. We developed a decision-making task for head-fixed mice in which we varied the expected value and risk associated with reward-predicting stimuli. Using large-scale electrophysiology and projection-specific optotagging across multiple frontal regions, we identified distinct spatial gradients for these variables, with stronger expected value coding in dorsal regions and stronger risk coding in medial regions. We then demonstrated that this encoding further depends on the neuronal projections: frontal neurons projecting to the dorsomedial striatum and claustrum differentially encoded economic variables. Our findings illustrate that frontal cortical representation of economic variables is jointly determined by spatial organization and downstream connectivity of neurons, revealing a structured, multi-scale code for economic variables.
Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’s Disease: Linking Cellular Dysfunction to Cognitive Decline
Authors: Adlimoghaddam Aida , Fayazbakhsh Fariba , Mohammadi Mohsen , Babaei Zeinab , Behrooz Amir Barzegar , Tabasi Farhad , Guan Teng , Beheshti Iman , Aghaei Mahmoud , Klionsky Daniel J , Albensi Benedict C. , Ghavami Saeid
Published: October 2024

Macroautophagy and mitophagy are critical processes in Alzheimer’s disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, are not fully understood. This study investigates autophagy (LC3B-II, SQSTM1) and mitophagy (BNIP3L, BNIP3, BCL2L13) markers in the cortex and hippocampus of male and female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), and behavioral tests (novel object recognition and novel object placement).

Significant sex-specific differences emerged: female 3xTg-AD mice exhibited autophagosome accumulation due to impaired degradation in the cortex, while males showed fewer autophagosomes, especially in the hippocampus, without significant degradation changes. TEM analyses demonstrated variations in mitochondrial and mitophagosome numbers correlated with memory outcomes. Females had enhanced mitophagy, with higher BNIP3L and BCL2L13 levels, whereas males showed elevated BNIP3 dimers. Cognitive deficits in females correlated with mitochondrial dysfunction in the cortex, while in males, higher LC3B-II levels associated positively with cognitive performance, suggesting protective autophagy effects.

Using machine learning, we predicted mitophagosome and mitochondrial numbers based on behavioral data, pioneering a predictive approach to cellular outcomes in AD. These findings underscore the importance of sex-specific regulation of autophagy and mitophagy in AD and support personalized therapeutic approaches targeting these pathways. Integrating machine learning emphasizes its potential to advance neurodegenerative research.

Abstract Figure

Graphical Abstract

Sex-specific differences in autophagy and mitophagy regulation in Alzheimer’s disease (AD) are highlighted. Female 3xTg-AD mice show autophagosome accumulation and cognitive deficits, while males exhibit variations in mitophagy markers and behavior.
Abstract rule generalization for composing novel meaning recruits the frontoparietal control network
Authors: Zheng Xiaochen Y. , Garvert Mona M. , den Ouden Hanneke E. M. , Horstman Lisa I. , Richter David , Cools Roshan
Published: October 2024

The ability to generalize previously learned knowledge to novel situations is crucial for adaptive behavior, representing a form of cognitive flexibility that is particularly relevant in language. Humans excel at combining linguistic building blocks to infer the meanings of novel compositional words, such as “un-reject-able-ish”. How do we accomplish this? While recent research on compositional generalization in relational memory, action planning and vision strongly implicates a medial prefrontal-hippocampal network (Baram et al., 2021; Barron et al., 2020; Schwartenbeck et al., 2023), it remains unclear whether the same network supports compositional inference in language. To this end, we trained participants on an artificial language in which the meanings of compositional words could be derived from known stems and unknown affixes, using abstract affixation rules (e.g., “good-kla” which means “bad”, where “-kla” reverses the meaning of the stem word “good”). According to these rules, word meaning depended on the sequential relation between the stem and the affix (i.e., pre- vs. post-stem). During fMRI, participants performed a semantic priming task, with novel compositional words as either sequential order congruent (e.g., “white-kla”) or incongruent primes (e.g., “kla-white”), and synonyms of the composed meaning as targets (“black”). Our results show that the compositional process engages a broad temporoparietal network, including the hippocampus, while the composed meanings are represented in left-lateralized language areas. Notably, newly composed meanings were decodable already at the time of the prime. Finally, we found that the composition process recruits abstract structure rule representations in a lateral frontoparietal network, rather than the predicted medial frontotemporal network, perhaps because abstract rules in language are more readily formatted as production rules rather than as relational map structures.
Impacts ofperRon oxygen sensitivity, gene expression, and murine infection inClostridioides difficile630Δerm
Authors: Gregory Anna L. , Bussan Hailey E. , Topf Madeline A. , Hryckowian Andrew J.
Published: October 2024

Clostridioides difficileinfection (CDI), characterized by colitis and diarrhea, afflicts approximately half a million people in the United States every year, burdening both individuals and the healthcare system.C. difficile630Δermis an erythromycin-sensitive variant of the clinical isolateC. difficile630 and is commonly used in theC. difficileresearch community due to its genetic tractability. 630Δermpossesses a point mutation inperR, an autoregulated transcriptional repressor that regulates oxidative stress resistance genes. This point mutation results in a constitutively de-repressed PerR operon in 630Δerm. To address the impacts ofperRon phenotypes relevant for oxygen tolerance and relevant to a murine model of CDI, we corrected the point mutant to restore PerR function in 630Δerm(herein, 630Δerm perRWT). We demonstrate that there is no difference in growth between 630Δermand a 630Δerm perRWTunder anaerobic conditions or when exposed to concentrations of O2that mimic those found near the surface of the colonic epithelium. However, 630Δerm perRWTis more sensitive to ambient oxygen than 630Δerm, which coincides with alterations in expression of a variety ofperR-dependent andperR-independent genes. Finally, we show that 630Δermand 630Δerm perRWTdo not differ in their ability to infect and cause disease in a well-established murine model of CDI. Together, these data support the hypothesis that theperRmutation in 630Δermarose as a result of exposure to ambient oxygen and that theperRmutation in 630Δermis unlikely to impact CDI-relevant phenotypes in laboratory studies.

Importance

Clostridioides difficileis a diarrheal pathogen and a major public health concern. To improve humans’ understanding ofC. difficile, a variety ofC. difficileisolates are used in research, includingC. difficile630Δerm. 630Δermis a derivative of the clinical isolate 630 and is commonly studied because it is genetically manipulable. Previous work showed that a mutation inperRin 630Δermresults in a dysregulated oxidative stress response, but no work has been done to characterizeperR-dependent effects on the transcriptome or to determine impacts ofperRduring infection. Here, we identify transcriptomic differences between 630Δerm and630Δerm perRWTexposed to ambient oxygen and demonstrate that there is no strain-based difference in burdens in murineC. difficileinfection.
Spatiotemporal map of the developing human reproductive tract at single-cell resolution
Authors: Lorenzi Valentina , Mazzeo Cecilia Icoresi , Yayon Nadav , Ruiz-Morales Elias R. , Sancho-Serra Carmen , Wong Frederick C.K. , Marečková Magda , Tuck Liz , Roberts Kenny , Li Tong , Jacques Marc-Antoine , He Xiaoling , Barker Roger , Crespo Berta , Cakir Batuhan , Murray Simon , Prete Martin , Gu Yong , Kelava Iva , Garcia Alonso Luz , Marioni John C , Tormo Roser Vento
Published: October 2024

The human reproductive tract plays an essential role in species perpetuation. Its development involves complex processes of sex specification, tissue patterning and morphogenesis, which, if disrupted, can cause lifelong health issues, including infertility. Here, we generated an extensive single-cell and spatial multi-omic atlas of the human reproductive tract during prenatal development, which allowed us to answer questions that smaller-scale, organ-focused experiments could not address before. We identified potential regulators of sexual dimorphism in reproductive organs, pinpointing novel genes involved in urethral canalisation of the penis, with relevance to hypospadias. By combining histological features with gene expression data, we defined the transcription factors and cell signalling events required for the regionalisation of the Müllerian and Wolffian ducts. This led to a refinement of how theHOXcode is established in the distinct reproductive organs, including increased expression of thoracicHOXgenes in the rostral mesenchyme of the fallopian tube and epididymis. Our study further revealed that the epithelial regionalisation of the fallopian tube and epididymis required for sperm maturation in adulthood is established early in development. In contrast, later events in gestation or postnatally are necessary for the regionalisation of the uterocervical canal epithelium. By mapping sex-specific reproductive tract regionalisation and differentiation at the cellular level, our study offers valuable insights into the causes and potential treatments of reproductive disorders.
The persistent effects of predator odor stressor enhance interoceptive sensitivity to alcohol through GABAAreceptor adaptations in the prelimbic cortex in male, but not female rats
Authors: Tyler Ryan E. , Bluitt Maya N. , Van Voorhies Kalynn J. , Liu Wen , Magee Sarah N. , Pitrolo Elisabeth R. , Cordero Victoria L. , Ornelas Laura C. , Krieman Caroline G. , Bender Brooke N. , Mosera Alejandro M. , Besheer Joyce
Published: October 2024

Background

Traumatic stress is associated with high rates of problematic alcohol use, but how the persistent effects of trauma impact sensitivity to alcohol remain unknown. This study examined the persistent effects of traumatic stress exposure on sensitivity to alcohol and underlying neurobiological mechanisms in rats.

Methods

Male (N=98) and female (N=98) Long-Evans rats were exposed to the predator odor TMT, and two weeks later, molecular, neuronal, and behavioral sensitivity to alcohol were assessed. Next, rats were trained to discriminate alcohol from water (male N=70; female N=56), and the impact of TMT on interoceptive sensitivity to alcohol and the alcohol-like effects of systemic GABAAreceptor activation were evaluated. Lastly, functional involvement of GABAAand NMDA receptors in the prelimbic cortex (PrL) and the anterior insular cortex (aIC) was investigated.

Results

TMT exposure sex-dependently altered PrLGabra1, and elevated aICGrin2bandGrin2cin males. TMT increased PrL c-Fos in males, which was attenuated by alcohol administration. Alcohol-induced locomotor and startle response effects were attenuated in the TMT group in both sexes. TMT exposure potentiated interoceptive sensitivity to alcohol in males but not in females, and this effect was driven by GABAAreceptors in the PrL. Greater stress reactivity during TMT exposure was associated with higher interoceptive sensitivity to alcohol, and alcohol exposure history was linked to a heightened stress response to TMT in males.

Conclusions

Traumatic stress increased interoceptive sensitivity to alcohol in males, but not females, through PrL GABAAreceptor adaptations, potentially enhancing the stimulatory, and by extension the rewarding, effects of alcohol.
Retinal microglia-derived S100A9 incite NLRP3 inflammasome in a Western diet fed Ossabaw pig retina
Authors: Lim Rayne R , Thomas Anju , Ramasubramanian Aparna , Chaurasia Shyam S.
Published: October 2024

Purpose

We established S100A9 as a myeloid-derived damage-associated molecular pattern (DAMPs) protein associated with increasing severity of diabetic retinopathy (DR) in type 2 diabetic subjects. The present study investigates the retinal localization, expression, and mechanisms of action for S100A9 in the young obese Ossabaw pig retina.

Methods

Retinae from Ossabaw pigs fed a Western diet for 10 weeks were evaluated for S100 and inflammatory mediator expression using quantitative PCR and Western blot. Double immunohistochemistry was performed to identify the cellular sources of S100A9 in the pig retina. Primary pig retinal microglial cells (pMicroglia) were examined for S100A9 production. S100A9-induced responses were also investigated, and inhibitor studies elucidated the mechanism of action via the NLRP3 inflammasome. A specific inhibitor, Paquinimod (ABR-215757), was administeredin vitroto assess the rescue of S100A9-induced NLRP3 inflammasome activation in pMicroglia.

Results

The expression of the S100 family in the obese Ossabaw pig retina showed a significant elevation of S100A9, consistent with increased levels of circulating S100A9. Moreover, the retina had elevated levels of inflammatory mediators IL-6, IL-8, MCP-1, IL-1β and NLRP3. Retinal microglia in obese Ossabaw were activated and accompanied by an increased expression of intracellular S100A9. pMicroglia isolated from pig retina transformed from ramified to amoeboid state when activated with LPS and produced high S100A9 transcript and protein levels. The S100A9 protein, in turn, further activated pMicroglia by heightened production of S100A9 transcripts and secretion of pro-inflammatory IL-1β protein. Inhibition of TLR4 with TAK242 and NLRP3 with MCC950 attenuated the production of IL-1β during S100A9 stimulus. Finally, pre-treatment with Paquinimod successfully reduced S100A9-driven increases of glycosylated-TLR4, NLRP3, ASC, Caspase-1, and IL-1β production.

Conclusion

We demonstrated that microglial-derived S100A9 perpetuates pro-inflammatory responses via the NLRP3 inflammasome in the retina of young Western-diet-fed Ossabaw pigs exhibiting diabetic retinopathy.
Massively parallel experimental interrogation of natural variants in ancient signaling pathways reveals both purifying selection and local adaptation
Authors: Aguilar-Rodríguez José , Vila Jean , Chen Shi-An A. , Razo-Mejia Manuel , Ghosh Olivia , Fraser Hunter B. , Jarosz Dan F. , Petrov Dmitri A.
Published: October 2024

The nature of standing genetic variation remains a central debate in population genetics, with differing perspectives on whether common variants are mostly neutral or have functional effects. We address this question by directly mapping the fitness effects of over 9,000 natural variants in the Ras/PKA and TOR/Sch9 pathways—key regulators of cell proliferation in eukaryotes—across four conditions inSaccharomyces cerevisiae. While many variants are neutral in our assay, on the order of 3,500 exhibited significant fitness effects. These non-neutral variants tend to be missense and affect conserved, more densely packed, and less solvent-exposed protein regions. They are also typically younger, occur at lower frequencies, and more often found in heterozygous states, suggesting they are subject to purifying selection. A substantial fraction of non-neutral variants showing strong fitness effects in our experiments, however, is present at high frequencies in the population. These variants show signs of local adaptation as they tend to be found specifically in domesticated strains adapted to human-made environments. Our findings support the view that while common variants are often neutral, a significant proportion have adaptive functional consequences and are driven into the population by local positive selection. This study highlights the potential to explore the functional effects of natural genetic variation on a genome scale with quantitative fitness measurements in the laboratory, bridging the gap between population genetics and functional genomics to understand evolutionary dynamics in the wild.
Contrasting macroevolutionary patterns in the human N-glycosylation pathway
Authors: Kifer Domagoj , Čorak Nina , Domazet-Lošo Mirjana , Kasalo Niko , Lauc Gordan , Klobučar Göran , Domazet-Lošo Tomislav
Published: October 2024

Building on coding mutations and splicing variants, post-translational modifications add a final layer to protein diversity that operates at developmental and physiological timescales. Although protein glycosylation is one of the most common post-translational modifications, its evolutionary origin remains largely unexplored. Here, we performed a phylostratigraphic tracking of glycosylation machinery genes and their targets — glycosylated proteins — in a broad phylogenetic context. Our results show that the vast majority of human glycosylation machinery genes trace back to two evolutionary periods: the origin of all cellular organisms and the origin of all eukaryotes. This indicates that protein glycosylation is an ancient process likely common to all life, further elaborated in early eukaryotes. In contrast, human glycoproteins exhibited prominent enrichment signals in more recent evolutionary periods, suggesting an important role in the transition from metazoans to vertebrates. Focusing specifically on the N-glycosylation pathway, we noted that the majority of N-glycosylation genes acting on the cytoplasmic side of the endoplasmic reticulum (ER) trace back to the origin of cellular organisms. This sharply contrasts with the rest of the N-glycosylation pathway, which is oriented toward the ER lumen, where genes of eukaryotic origin predominate. In the Golgi, we also identified an analogous binary evolutionary origin of glycosylation machinery genes. We discuss these findings in the context of the evolutionary emergence of the eukaryotic endomembrane system and propose that the ER evolved through the invagination of a prokaryotic cell membrane containing an N-glycosylation pathway.
Single-cell profiling of cortical tubers in tuberous sclerosis complex shows molecular structure preservation and massive reorganization of metabolism
Authors: Friis Sørensen Frederik Nørby , Petanjek Tin Luka , Scheper Mirte , Rydbirk Rasmus , Korshunova Irina , Anink Jasper , Mühlebner Angelika , Mills James D. , Petanjek Zdravko , Aronica Eleonora , Khodosevich Konstantin
Published: October 2024

Tuberous sclerosis complex (TSC) is a multisystemic genetic disorder associated with loss-of-function mutations in theTSC1orTSC2gene, which lead mTOR pathway hyperactivation and epileptogenesis. Cortical tubers are the hallmark of TSC and represent disorganized cortical structure underlying the generation of focal seizures. Here, we report single-nucleus RNA sequencing in resected cortical tubers vs matched pediatric controls. Strikingly, in spite of severe cortical disorganization, we found that cortical tubers preserve all neuronal subtypes, even the rarest ones. Moreover, we showed that principal neurons largely preserve spatial position based on transcriptional signatures. Principal neurons and layer 1-2 GABAergic neurons that modulate upper cortical circuits exhibited the largest gene expression changes. Interestingly, multiple mTOR pathway gene expression changes in TSC counteracted mTOR hyperactivation. TSC neuronal, but not glial, networks exhibited massive metabolic reorganization with a reduction in mitochondrial respiration and a concomitant switch to fatty acid metabolism. Finally, we show that neuron-specific AMPA receptor signaling might underlie epileptogenesis in TSC and could represent a potential candidate for therapeutic targeting.
Sleep Deprivation in Mice: Looking Beyond the Slow Wave Rebound
Authors: Magyar Tárek Zoltán , Szalárdy Orsolya , Bódizs Róbert
Published: October 2024

Sleep is a fundamental process by which the brain achieves an optimal computational regime; it has been suggested that criticality is an appropriate theoretical framework in which such a process can be understood. Studying the critical and fractal dynamics of the brain involves modelling the nonlinearity of brain signals (such as EEG or ECoG) yielding, among others, the following metrics: spectral slope, spectral intercept, spectral knee, and normalized spectral entropy. Therefore, the present study investigates the nonlinear and critical dynamics of the brain in relation to sleep deprivation in mice, by comparing the sensitivity of the above-mentioned metrics to classical band- limited spectral indices. Mice were exposed to a 9 day-long sleep deprivation paradigm with baseline, sleep deprivation, and recovery phases. Spectral parameters were computed using the FOOOF algorithm. The results suggest that the classical approach (slow wave activity; 0.75-4.5 Hz) to neural signal processing differentiates between baseline sleep and rebound sleep only during the NREM phase. In contrast, the spectral slope and the spectral intercept both capture sleep deprivation related effects during REM and NREM episodes as well. This is particularly notable considering that the spectral knee is shifted towards higher frequencies, essentially rendering the spectral slope unreflective of slow wave activity – traditionally considered the biomarker of sleep homeostasis.

Lastly, normalized spectral entropy fails to differentiate between baseline sleep and sleep following sleep deprivation in mice. These results support the sensitivity of fractal spectral parameters indexing the intricate balance between sleep and wake states.
Infrared finite scattering theory: Amplitudes and soft theorems
Authors: Prabhu Kartik , Satishchandran Gautam
Published: October 2024

Any nontrivial scattering with massless fields in four spacetime dimensions will generically produce an out-state with memory. Scattering with any massless fields violates the standard assumption of asymptotic completeness—that all “in” and “out” states lie in the standard (zero-memory) Fock space—and therefore leads to infrared divergences in the standard S-matrix amplitudes. In this paper, we define an infrared finite scattering theory which assumes only (1) the existence of in-/out-algebras and (2) that Heisenberg evolution is an automorphism of these algebras. The resulting “superscattering” map $ allows for transitions between different in/out memory states and agrees with the standard S matrix when it is defined. We construct $ amplitudes by defining (3) a “generalized asymptotic completeness” which accommodates states with memory in the space of asymptotic states and (4) a complete basis of improper states that generalize the usual n-particle momentum basis to account for states with memory. Using only general properties of $, we prove an analog of the Weinberg soft theorems in quantum gravity and QED which imply that all $ amplitudes are well defined in the infrared. We comment on how one must generalize this framework to consider $ amplitudes for theories with collinear divergences (e.g., massless QED and Yang-Mills theories).

Published by the American Physical Society
2024
Time-Dependent Hamiltonian Simulation Using Discrete-Clock Constructions
Authors: Watkins Jacob , Wiebe Nathan , Roggero Alessandro , Lee Dean
Published: October 2024

Compared with time-independent Hamiltonians, the dynamics of generic quantum Hamiltonians H(t) are complicated by the presence of time ordering in the evolution operator. In the context of digital quantum simulation, this difficulty prevents a direct adaptation of many time-independent simulation algorithms for time-dependent simulation. However, there exists a framework within the theory of dynamical systems that eliminates time ordering by adding a “clock” degree of freedom. In this work, we provide a computational framework, based on this reduction, for encoding time-dependent dynamics as time-independent systems. As a result, we make two advances in digital Hamiltonian simulation. First, we create a time-dependent simulation algorithm based on performing qubitization on the augmented clock system and, in doing so, provide the first qubitization-based approach to time-dependent Hamiltonians that goes beyond Trotterization of the ordered exponential. Second, we define a natural generalization of multiproduct formulas for time-ordered exponentials and then propose and analyze an algorithm based on these formulas. Unlike other algorithms of similar accuracy, the multiproduct approach achieves commutator scaling, meaning that this method outperforms existing methods for physically local time-dependent Hamiltonians with sufficient smoothness. Our work reduces the disparity between time-dependent and time-independent simulation and indicates a step toward optimal quantum simulation of time-dependent Hamiltonians.

Published by the American Physical Society
2024
Salts of 2-amino-5-iodopyridinium
Authors: Mukda Benjamin A. , Dickie Diane A. , Turnbull Mark M.
Published: October 2024

Reaction of 2-amino-5-iodopyridine (5IAP) with concentrated HBr at room temperature yielded 2-amino-5-iodopyridinium bromide, C5H6IN2
+·Br− or (5IAPH)Br. The complex formed pale-yellow crystals, which exhibit significant hydrogen bonding between the amino and pyridinium N—H donors and bromide ion acceptors. Halogen bonding is also observed. Similarly, reaction of 5IAP with cobalt(II) chloride in mixed HCl/HBr in 1-propanol yielded 2-amino-5-iodopyridinium (2-amino-5-iodopyridine-κN
1)bromido/chlorido(0.51/2.48)cobalt(II), (C5H6IN2)[CoBr0.51Cl2.48(C5H5IN2)] or (5-IAPH)[(5IAP)CoCl2.48Br0.51], as blue block-shaped crystals. Two of the three halide positions exhibit mixed occupancy [Cl/Br = 0.797 (5):0.203 (5) and 0.689 (6):0.311 (6)], while the third position is occupied solely by a chloride ion. Extensive hydrogen and halogen bonding is observed.
Crystal structure and Hirshfeld surface analysis of the salt 2-iodoethylammonium iodide – a possible side product upon synthesis of hybrid perovskites
Authors: Petrosova Hanna R. , Naumova Dina D. , Golenya Irina A. , Buta Ildiko , Gural'skiy Il'ya A.
Published: October 2024

The title organic–inorganic hybrid salt, C2H7IN+·I−, is isotypic with its bromine analog, C2H7BrN+·Br− [Semenikhin et al. (2024). Acta Cryst. E80, 738–741]. Its asymmetric unit consists of one 2-iodoethylammonium cation and one iodide anion. The NH3
+ group of the organic cation forms weak hydrogen bonds with four neighboring iodide anions, leading to the formation of supramolecular layers propagating parallel to the bc plane. Hirshfeld surface analysis reveals that the most important contribution to the crystal packing is from N—H...I interactions (63.8%). The crystal under investigation was twinned by a 180° rotation around [001].
(1H-Benzodiazol-2-ylmethyl)diethylamine
Authors: Khamrang Themmila , Kannan A. , Hemamalini Madhukar , Tahir Muhammad Nawaz , Antony G. Jerald Maria , Saravanan Dhandayutham
Published: October 2024

In the crystal of the title compound, C12H17N3, the molecules are linked by N—H...N hydrogen bonds, generating a C(4) chain extending along the c-axis direction. One of the ethyl groups is disordered over two sets of sites with a refined occupancy ratio of 0.582 (15):0.418 (15).
Benzilic acid: a monoclinic polymorph
Authors: Prinsloo Petrus , Hosten Eric Cyriel , Betz Richard
Published: October 2024

The title compound, C14H12O3, is an α-hydroxycarboxylic acid whose orthorhombic polymorph has been reported earlier [Qiu et al. (2007). Inorg. Chim. Acta, 360, 1819–1824]. The asymmetric unit contains two complete molecules. Classical hydrogen bonds, as well as C—H...O contacts, connect the molecules to infinite chains along the crystallographic c-axis direction.
Enhancing hydrologic LiDAR digital elevation models: Bridging hydrographic gaps at fine scales
Authors: Wu Di , Li Ruopu , Edidem Michael , Wang Guangxing
Published: October 2024

High‐resolution digital elevation models (HRDEMs), derived from LiDAR, are widely used for mapping hydrographic details in flat terrains. However, artificial flow barriers, particularly from roads, elevate terrain and prematurely end flowlines. Drainage barrier processing (DBP), such as HRDEM excavation, is employed to address this issue. However, there is a gap in quantitatively assessing the impact of DBP on HRDEM‐derived flowlines, especially at finer scales. This study fills that gap by quantitatively assessing how DBP improves flowline quality at finer scales. We evaluated HRDEM‐derived flowlines that were generated using different flow direction algorithms, developing a framework to measure the effects of flow barrier removal. The results show that the primary factor influencing flowline quality is the presence of flow accumulation artifacts. Quality issues also stem from differences between natural and artificial flow paths, unrealistic flowlines in flat areas, complex canal networks, and ephemeral drainage ways. Notably, the improvement achieved by DBP is demonstrated to be more than 6%, showcasing its efficacy in reducing the impact of flow barriers on hydrologic connectivity.
Quantitative analysis of imaging characteristics in lung adenocarcinoma in situ using artificial intelligence
Authors: Shi Wensong , Hu Yuzhui , Yang Yulun , Song Yinsen , Chang Guotao , Qian He , Wei Zhengpan , Gao Liang , Sun Yingli , Li Ming , Yi Hang , Wu Sikai , Wang Kun , Mao Yousheng , Ai Siyuan , Zhao Liang , Zheng Huiyu , Li Xiangnan
Published: October 2024

Background

With the rising incidence of pulmonary nodules (PNs), lung adenocarcinoma in situ (AIS) is a critical early stage of lung cancer, necessitating accurate diagnosis for early intervention. This study applies artificial intelligence (AI) for quantitative imaging analysis to differentiate AIS from atypical adenomatous hyperplasia (AAH) and minimally invasive adenocarcinoma (MIA), aiming to enhance clinical diagnosis and prevent misdiagnosis.

Methods

The study analyzed 1215 PNs with confirmed AAH, AIS, and MIA from six centers using the Shukun AI diagnostic module. Parameters evaluated included demographic data and various CT imaging metrics to identify indicators for clinical application, focusing on the mean CT value's predictive value.

Results

Significant differences were found in several parameters between AAH and AIS, with nodule mass showing the highest predictive value. When comparing AIS to MIA, total nodule volume was the best predictor, followed by the maximum CT value.

Conclusion

The mean CT value has limited discriminative power for AIS diagnosis. Instead, the maximum CT value and maximum 3D diameter are recommended for clinical differentiation. Nodule mass and volume of solid components are strong indicators for differentiating AIS from AAH and MIA, respectively.
Application of machine learning in predicting health perception through military personnel's sense of empowerment
Authors: Chen Kun‐Huang , Chiu Pao‐Lung , Chen Ming‐Hsuan
Published: October 2024

The promotion of health and provision of care services for new recruits are issues of constant concern for military leaders and healthcare providers, as they are crucial to maintaining and operating military forces. The enhancement of military personnel's empowerment has been recognized as a core value in promoting health perception. However, the pathways between military personnel's sense of empowerment and health perception have not been thoroughly explored. The primary aim of this study is to examine the predictive power of different dimensions of empowerment (personal, interpersonal, and socio‐political) on new recruits' health perception, and to further observe differences among subgroups, which will help us grasp the nuances of future health intervention measures. The research data were extracted from the “Military Career Development Study,” analyzing personal empowerment data from Wave 1 (W1) and perceived health data from Wave 2 (W2) (N = 2,232). In terms of analytical methods, five ML classifiers, including Decision Tree, Random Forest, Support Vector Machine, AdaBoost, and k‐Nearest Neighbors (KNN) algorithms, were used for prediction in both the full sample and subsamples (gender and socioeconomic status). Results show that among the five ML classifiers, the Decision Tree performed best overall, achieving a prediction accuracy of 95.4%. The results by gender show that the ML models perform best for both males and females with the Decision Tree and Random Forest methods. For the Decision Tree, the accuracy rates were 94.9% for males and 95.1% for females; the F1 scores were 92.9% for males and 93.2% for females. For the Random Forest, the accuracy rates were 94.9% for males and 95.4% for females; the F1 scores were 92.7% for males and 93.2% for females. Regarding SES, the Decision Tree and Random Forest methods performed best. In the SES Low group, both methods achieved a prediction accuracy of 95.6% and an F1 score of 93.7%; in the SES high group, they achieved a prediction accuracy of 95.4% and an F1 score of 93.3%. However, the contribution of different dimensions of empowerment features varied significantly among subgroups. These findings can provide important information on the differences in health perception among military personnel.
Distal preservation and retrograde resection of the anterior vaginal wall in female robot‐assisted radical cystectomy
Authors: Iguchi Ryo , Inoue Koji
Published: October 2024

Introduction

In many cases of female radical cystectomy for bladder cancer, the procedure involves simultaneous removal of the uterus, fallopian tubes, ovaries, anterior vaginal wall, and urethra. After this procedure, rare complications like vaginal dehiscence and evisceration may occur. We herein describe this article surgical technique involving preservation of the distal anterior vaginal wall to maintain pelvic floor strength and retrograde resection of the proximal anterior vaginal wall.

Materials and Surgical Technique

The presented case was a 61‐year‐old woman who had a bladder tumor. After undergoing a transurethral resection, the pathology revealed muscle‐invasive squamous cell bladder cancer. Consequently, she received a robot‐assisted radical cystectomy (RARC) without neoadjuvant chemotherapy. Before opening the vaginal wall, the urethra, including the external urethral meatus, was dissected along its entire length. Next, a transverse incision was made in the anterior vaginal wall at the level of bladder neck, and the wall was resected retrogradely toward the anterior vaginal fornix while preserving the distal anterior vaginal wall. The opened vaginal wall was closed in a tubular shape.

Discussion

Preservation of the distal anterior vaginal wall and retrograde anterior vaginal wall resection can be safely performed in female RARC and may reduce the risk of vaginal dehiscence by minimizing the vaginal wall defect.
Isolated esophageal hiatal hernia of the colon: A case report and review of literature
Authors: Maeda Shinsuke , Ito Shunichi , Hosoda Kei
Published: October 2024

Esophageal hiatal hernias, most of which are transhiatal migrations of the gastric cardia into the mediastinum, include a minor category called paraesophageal hernias. Herniation of organs other than the stomach belongs to this category. A 75‐year‐old man who developed esophageal hiatal hernia of an isolated transverse colon underwent elective laparoscopic surgery. Intraoperative findings revealed a preserved phrenoesophageal attachment on the patient's left dorsal side. Sac excision, sutured cruroplasty, and Toupet fundoplication were performed. The postoperative course was uneventful, and the patient's stooping‐induced dyspnea was relieved after surgery. Our literature review indicated that hiatal hernia of the isolated colon has the unique characteristic of causing secondary gastroduodenal outlet obstruction and shares a mutual nature with Type II hiatal hernia. Although rare, this uncommon type of hiatal hernia may be recognized as a distinct subtype of paraesophageal hernia.
Research on the P‐S‐N Curve Fitting Method of Notched Specimens Considering Small Sample Properties
Authors: Zhang Ziyang , Liu Jianhui , Hu Juntai , Wu Qingjun , Wu Shenglei
Published: October 2024

Aiming at the issue of fatigue test data for large‐scale mechanical components of building steel are very limited, a method for fitting P‐S‐N curves under small sample data of notched specimens is proposed to predict fatigue life. First, a fatigue life subsample augmented and its reliability assessment method are established, based on Bayesian hierarchical modeling and modified Monte Carlo method. Second, a clustering combination weighting method is proposed, to define weights of hidden variables of the binomial mixture Weibull distribution, and the expectation–maximization algorithm is used to determine probability density function of the distribution. Finally, the P‐S‐N curves under various failure probabilities are fitted with Weibull distributed life models, and the convergence and prediction accuracy of the different models are compared. The results show that the fatigue data of small samples can be predicted better by using mixed Weibull distribution, and the fitting P‐S‐N curve is more reliable and accurate.
Ki‐67 evaluation using deep‐learning model‐assisted digital image analysis in breast cancer
Authors: Matsumoto Hirofumi , Miyata Ryota , Tsuruta Yuma , Nakada Norihiro , Koki Ayako , Unesoko Mikiko , Abe Norie , Zaha Hisamitsu
Published: October 2024

Aims

To test the efficacy of artificial intelligence (AI)‐assisted Ki‐67 digital image analysis in invasive breast carcinoma (IBC) with quantitative assessment of AI model performance.

Methods and Results

This study used 494 cases of Ki‐67 slide images of IBC core needle biopsies. The methods were divided into two steps: (i) construction of a deep‐learning model (DL); and (ii) DL implementation for Ki‐67 analysis. First, a DL tissue classifier model (DL‐TC) and a DL nuclear detection model (DL‐ND) were constructed using HALO AI DenseNet V2 algorithm with 31,924 annotations in 300 Ki‐67 digital slide images. Whether the class predicted by DL‐TC in the test set was correct compared with the annotation of ground truth at the pixel level was evaluated. Second, DL‐TC‐ and DL‐ND‐assisted digital image analysis (DL‐DIA) was performed in the other 194 luminal‐type cases and correlations with manual counting and clinical outcome were investigated to confirm the accuracy and prognostic potential of DL‐DIA. The performance of DL‐TC was excellent and invasive carcinoma nests were well segmented from other elements (average precision: 0.851; recall: 0.878; F1‐score: 0.858). Ki‐67 index data and the number of nuclei from DL‐DIA were positively correlated with data from manual counting (ρ = 0.961, and 0.928, respectively). High Ki‐67 index (cutoff 20%) cases showed significantly worse recurrence‐free survival and breast cancer‐specific survival (P = 0.024, and 0.032, respectively).

Conclusion

The performances of DL‐TC and DL‐ND were excellent. DL‐DIA demonstrated a high degree of concordance with manual counting of Ki‐67 and the results of this approach have prognostic potential.
Analytic mappings of the unit disk which almost preserve hyperbolic area
Authors: Ivrii Oleg , Nicolau Artur
Published: October 2024

In this paper, we study analytic self‐maps of the unit disk which distort hyperbolic areas of large hyperbolic disks by a bounded amount. We give a number of characterizations involving angular derivatives, Lipschitz extensions, Möbius distortion, the distribution of critical points and Aleksandrov–Clark measures. We also examine the Lyapunov exponents of their Aleksandrov–Clark measures.
High-resolution chemical patterns from negative tone resists for the integration of extreme ultraviolet patterns of metal-oxide resists with directed self-assembly of block copolymers
Authors: Lee Kyunghyeon , Vargo Emma , Eom Christopher , Ruiz Ricardo , Nealey Paul F.
Published: October 2024

Extreme ultraviolet (EUV) lithography faces significant challenges in designing suitable resist materials that can provide adequate precision, while maintaining economically viable throughput. These challenges in resist materials have led to printing failures and high roughness in EUV patterns, compromising the performance of semiconductor devices. Integrating directed self-assembly (DSA) of block copolymers (BCPs) with EUV lithography offers a promising solution because, while the BCPs register to the EUV-defined chemical guiding pattern, the thermodynamically determined structures of the BCPs automatically rectify defects and roughness in the EUV pattern. Despite the superior resolution of metal-oxide EUV resists (MORs), their application to DSA is limited by the difficulty in converting them into chemical patterns that allow effective transfer of the rectified patterns of DSA films into inorganic materials. To address this challenge, this study introduces a novel strategy for fabricating chemical patterns using hydrogen silsesquioxane (HSQ), a high-resolution negative tone inorganic resist, as a model system for MORs. Initially, a sacrificial Cr pattern is generated from HSQ patterns via reactive ion etching. The sacrificial Cr pattern is converted into a chemical pattern by first grafting a water-soluble polyethylene oxide brush onto the substrate, then wet etching the Cr, and finally grafting nonpolar polystyrene brushes. Assembling polystyrene-block-poly(methyl methacrylate) on these patterns results in structures oriented and registered with the underlying pattern, achieving 24 nm full-pitch resolutions. This approach has the potential to integrate MOR patterns into the DSA process, thereby enabling the generation of high-quality sub-10 nm patterns with high-χ BCPs.
Two codependent routes lead to high-level MRSA
Authors: Adedeji-Olulana Abimbola Feyisara , Wacnik Katarzyna , Lafage Lucia , Pasquina-Lemonche Laia , Tinajero-Trejo Mariana , Sutton Joshua A. F. , Bilyk Bohdan , Irving Sophie E. , Portman Ross Callum J. , Meacock Oliver J. , Randerson Sam A. , Beattie Ewan , Owen David S. , Florence James , Durham William M. , Hornby David P. , Corrigan Rebecca M. , Green Jeffrey , Hobbs Jamie K. , Foster Simon J.
Published: October 2024

Methicillin-resistant
Staphylococcus aureus
(MRSA), in which acquisition of
mecA
[which encodes the cell wall peptidoglycan biosynthesis component penicillin-binding protein 2a (PBP2a)] confers resistance to β-lactam antibiotics, is of major clinical concern. We show that, in the presence of antibiotics, MRSA adopts an alternative mode of cell division and shows an altered peptidoglycan architecture at the division septum. PBP2a can replace the transpeptidase activity of the endogenous and essential PBP2 but not that of PBP1, which is responsible for the distinctive native septal peptidoglycan architecture. Successful division without PBP1 activity requires the alternative division mode and is enabled by several possible chromosomal potentiator (
pot
) mutations. MRSA resensitizing agents differentially interfere with the two codependent mechanisms required for high-level antibiotic resistance, which provides opportunities for new interventions.