bluuebunny/crossref_metadata_2025 huggingface dataset:
Polariton effects in the luminescence of solid xenon
Authors: Grigorashchenko O. N. , Savchenko E. V. , Fugol’ I. Ya.
Published: December 2024

A fine structure is detected in the luminescence spectrum of xenon crystals in the polariton mixing region near the edge of the Γ(3/2) excitonic states. The variation of the emission bands with temperature is determined. An analysis of the spectra makes it possible to determine the parameters of polariton theory and to construct the dispersion curves of volume and surface polaritons in xenon.
Effect of structural fluctuations on depth of penetration of longitudinal electric field into a superconducting film
Authors: Gogadze G. A. , Kulik I. O.
Published: December 2024

A consideration of scattering of quasiparticles by static inhomogeneities of the order parameter (structural fluctuations) leads to a temperature-independent depth of penetration of a longitudinal electric field into a thin superconducting film.
Equation of motion of the magnetic moment in the quasiclassical approximation
Authors: Popov V. A. , Loginov A. A.
Published: December 2024

An equation of motion is derived for the lattice-site magnetic moment in the quasiclassical approximation. It is shown that the presence of integrals of motion relating the components of the moment at each site prevents the derived equation from introducing new (in addition to the usual) spin-wave branches associated with variation of the magnitude of the moment vector.
Concentration dependence of the excess molar volumes of 3He–4He mixtures
Authors: Bogoyavlenskii I. V. , Karnatsevich L V. , Konareva V. G.
Published: December 2024

On the basis of dielectric constant measurements, P–V–T relationships are derived for the first time for 3He–4He mixtures at different 3He concentrations from 0 to 100% in the temperature range 4.5–9 °K and at pressures from 0.3 to 20 atm, i.e. in the range where the molar volumes of mixtures differ considerably from additive values. Excess molar volumes of the mixtures (VE) are calculated and the concentration dependence of VE is studied in the entire temperature and pressure range investigated. It is shown that in various temperature and pressure intervals the character of this dependence is different. For each composition there exists a region of P and T values where the concentration dependence of VE is sign-alternating. Calculations of VE on the basis of Prigogine’s model are carried out. It is shown that, on the whole, this theory describes the behavior of VE as a function of all the parameters, i.e., temperature, pressure, and 3He concentration, adequately. Quantitative discrepancy between theory and experiment is pronounced only at high densities, which is associated with the contribution of quantum-statistical effects to the excess functions of the 3He–4He system.
Response of a superconductor to a subcritical external current and a new possibility for determination of the effective resistance in the mixed state
Authors: Katyushkina L. V. , Shukhman V. A.
Published: December 2024

It is shown experimentally that shift of the magnetic vortex system of a superconductor in the mixed state under the influence of small changes in the external current, smaller than the critical current Ic, leads to the appearance of instability in the circuit measuring voltage across the superconductor, if the latter is a positive feedback element in such a circuit. It is shown that the development of instability is directly related to the loss resistance Rf, which is dependent solely on the properties of the superconductive matrix. The dependence of Rf on magnetic field is measured in the alloy In + 2.5 at. % Bi, and the data are compared with data obtained by traditional current–voltage characteristic methods.
Bulk nonlinear effect in the steady-state electrical conductivity of a metal specimen
Authors: Chiang Yu. N. , Ordynets A. G.
Published: December 2024

A method is described for obtaining a metal specimen with a dropping current-voltage characteristic. This effect has been realized in a single crystal of gallium within the 8–20 °K temperature range. The first data are presented pertaining to the features of this nonlinear effect in a metal.
Electrical conductivity of metal microcontacts containing magnetic impurities
Authors: Omel’yanchuk A. N. , Tuluzov I. G.
Published: December 2024

This study deals with the effect of electron scattering by impurities with localized magnetic moments on the electrical conductivity of a metal microcontact. It is demonstrated that the second derivative of the current with respect to the voltage (microcontact spectrum) contains a nonlinearity in the low-voltage range eV ∼ T (zero bias anomalies). The sign of a zero bias anomaly is determined by the sign of the exchange integral J.
Temperature dependence of the electrical resistance of amorphous bismuth films
Authors: Komnik Yu. F. , Belevtsev B. I.
Published: December 2024

The paper reports a study of the reversible temperature variation of the electrical resistance of thin (L = 10–130 Å) amorphous bismuth films deposited on substrates at liquid-helium temperatures. The superconducting fluctuations give rise to a small increase in the resistance near the superconducting transition temperature (Tc ≈ 2–5.5 °K). Above the temperature Tmax (∼ 10–14 °K) the resistance decreases, its variation being describable by the function R = R0 (1—ATn), which has been predicted for amorphous metals in a number of theoretical papers. When the contribution of the superconducting fluctuations at all arbitrarily high (as compared to Tc) temperatures is taken into account, the exponent n is equal to two in the vicinity of Tmax (up to ∼ 30 °K) and to unity at higher temperatures. When the contribution of the superconducting fluctuations at T > Tmax is neglected, the exponent n = 4 for the directly measured values. It turns out that the coefficient A depends on the film thickneess: it increases with decreasing the L. The observed laws governing the temperature dependence of the resistance of amorphous films are discussed on the basis of modem theoretical models.
Toward a theory of spin reorientation in rhombohedral antiferromagnetics
Authors: Soboleva T. K. , Stefanovskii E. P.
Published: December 2024

A theoretical study is made of the conditions under which spin reorientation in the basal plane of weak rhomohedral antiferromagnets in an external magnetic field occurs as a first order phase transition as the temperature is varied. Coordinates of the tricritical point are found on the plane H, T, (where H is the external magnetic field in the basal plane of the material and T is the temperature).
Absorption of energy from a low-frequency magnetic field by longitudinal pumping of an antiferromagnet
Authors: Borovikov V. S. , Frishman A. M.
Published: December 2024

Absorption of energy by a uniaxial antiferromagnet in an ac magnetic field parallel to the anisotropy axis is examined. It is shown that the power absorbed in slowly varying fields (ω ∼ 104-105 sec−1) can become quite large if the state is close to a second order phase transition. The results are compared with available experimental data.
The longitudinal magnetothermal emf of bismuth
Authors: Zhilyaev I. N. , Kopylov V. N.
Published: December 2024

It has been shown experimentally that the scattering of carriers by the surface of the specimen largely determines the behavior of the magnetothermal emf of bismuth at helium temperatures.
Stochastic properties of small antiferromagnetic particles
Authors: Gerus S. V. , Kharitonov V. D. , Lobanov E. A.
Published: December 2024

We study the dynamical properties of small antiferromagnetic particles. The Fokker-Planck equation is derived which describes the Brownian motion of the magnetic sublattices. The method of moments is used to calculate the longitudinal susceptibility of the antiferromagnetic particles in the case of “easy axis” and “easy plane” anisotropy. It is shown that, as the volume of the particles decreases, the static susceptibility tends to the finite value 4M0/3HE, where M0 is the magnetization of the sublattices and HE is the exchange field. For large particles, the influence of the thermal fluctuations falls, and the static susceptibility reaches its limiting value of zero for the “easy axis” type of antiferromagnetism, and to 2M0/HE for the “easy plane” type.
A novel hydraulic swing actuator with high torque density for legged robots
Authors: Zong Huaizhi , Ai Jikun , Fang Lizhou , Luo Yuanchun , Zhang Junhui , Xu Bing
Published: December 2024

Hydraulic swing actuators hold significant potential for legged robots due to their ability to deliver high torque directly to joints. However, their practical implementation is hindered by issues such as internal leakage, excessive size, and redundant weight, which restrict the dynamic performance of legged robots. To address these challenges, this paper proposes a novel circular swing hydraulic actuator that offers a compact design and a high torque-to-mass ratio inspired by the snail’s structures. First, the basic motion principle of the circular swing actuator is introduced, drawing from the snail’s spiral motion. Then, the split-shell mechanical structure with enhanced machinability and better assembly precision is presented, with a final dimension of ϕ153 × 70 mm3. Its mechanical properties are validated through numerical simulations and experiments, achieving a torque-to-weight ratio of 471.7 Nm kg−1. Additionally, a customized sealing system ensures minimal internal leakage and zero external leakage. Step response and position control experiments demonstrate that the actuator’s frequency response and tracking accuracy meet the requirements for legged robot joints driven by hydraulic systems. This circular swing actuator provides a promising solution for designing agile, high-performance legged robots.
Probabilistic inverse design of metasurfaces using mixture density neural networks
Authors: Torfeh Mahsa , Hsu Chia Wei
Published: December 2024

Metasurfaces are planar sub-micron structures that can outperform traditional optical elements and miniaturize optical devices. Optimization-based inverse designs of metasurfaces often get trapped in a local minimum, and the inherent non-uniqueness property of the inverse problem plagues approaches based on conventional neural networks. Here, we use mixture density neural networks to overcome the non-uniqueness issue for the design of metasurfaces. Once trained, the mixture density network (MDN) can predict a probability distribution of different optimal structures given any desired property as the input, without resorting to an iterative local optimization. As an example, we use the MDN to design metasurfaces that project structured light patterns with varying fields of view. This approach enables an efficient and reliable inverse design of fabrication-ready metasurfaces with complex functionalities without getting trapped in local optima.
Enhancing image quality in circular-view photoacoustic tomography using randomized detection points
Authors: Hakakzadeh Soheil , Rajendran Praveenbalaji , Kavehvash Zahra , Pramanik Manojit
Published: December 2024

Circular-view (circular scan) photoacoustic computed tomography (PACT) with low-density detection points (DPs) is an efficient, high-speed, and inexpensive modality with numerous (pre-) clinical applications. However, as the number of DPs decreases (decrease in A-lines), some unwanted streak artifacts appear in the reconstructed PACT image. Here, we present an approach to address the mentioned challenge and enhance image contrast. In this method, several low-resolution-images (LRIs) are reconstructed by employing a few DPs’ data with randomized locations. These LRIs are used in computing an artifact score matrix (ASM) to identify the location of artifacts. Three numerical (two vasculatures and human brain), two experimental (triangle and complex leaf), and an in vivo (a rat brain) studies were conducted to evaluate the efficacy of the proposed method (applying the computed ASM to the final reconstructed PA image). Our findings show that the proposed method outperforms conventional methods and offers better image quality. The signal-to-noise ratio and structural similarity index values of the proposed method are quantitatively 20 dB and 25% better than the conventional method, respectively. Furthermore, compared to the conventional method, the proposed method has an artifact standard deviation that is 50 times lower.
Diversity in Naturally Acquired Immunity to Group B Streptococcus: A Comparative Study of Women From Bangladesh, Malawi, and the United Kingdom
Authors: Khandaker Shadia , Sharma Shilpee , Hall Tom , Lim Suzanna , Lehtonen Janne , Leung Stephanie , Ahmed Zabed Bin , Gorringe Andrew , Saha Samir K , Marchant Arnaud , Le Doare Kirsty , Kadioglu Aras , French Neil
Published: December 2024

Background

Significant disparities in group B Streptococcus (GBS) colonization and neonatal disease rates have been documented across different geographic regions. For example, Bangladesh reports notably lower rates as compared with the United Kingdom and Malawi. This study investigates whether this epidemiologic variability correlates with the immune response to GBS in these regions.

Methods

Qualitative and quantitative analyses of naturally acquired immunoglobulin G (IgG) antibodies against GBS capsular polysaccharide and the Alp protein family were conducted in serum samples from women of childbearing age in the United Kingdom, Bangladesh, and Malawi. The efficacy of these antibodies in clearing vaginal colonization or protecting newborns from GBS infection was assessed with humanized mouse models.

Results

Bangladeshi women displayed the highest diversity in serotype distribution, with elevated IgG levels in the serum against GBS capsular polysaccharides Ia, Ib, II, III, IV, and V, as well as Alp family proteins. In contrast, Malawian sera demonstrated the weakest antibody response. Bangladeshi sera also showed heightened IgG-mediated complement deposition, opsonophagocytic killing, and neonatal Fc receptor binding while tested against capsular polysaccharide Ib. In a humanized neonatal Fc receptor mouse model, Bangladeshi sera led to faster clearance of GBS virulent serotype Ib vaginal colonization. Additionally, offspring from dams passively immunized with Bangladeshi sera demonstrated notably increased survival rates.

Conclusions

This study demonstrates significant variability in the immune response to GBS across different geographic regions. These findings underscore the importance of understanding GBS-induced immune response in diverse populations, which may significantly affect vaccine efficacy in these regions.
Arguing against the Brahmanical tradition: Dr B. R. Ambedkar’s engagement with the Manusmṛti
Authors: Khiamniungan Chiangmong
Published: December 2024

This essay attempts to provide an overview of Dr B. R. Ambedkar’s intense, extensive, and sustained examination and critique of what he took to be the ‘bible’ or ‘gospel’ of Brahmanism, the Manusmṛti. It will outline Ambedkar’s views concerning the significance of the text; undertake a survey of the primary and secondary sources Ambedkar relied on; present his arguments for the authorship and date of the text; indicate his argument about the sectarian and ideologically charged origin of the text; and, finally, elaborate his critique of the inegalitarian scheme that the text institutes. The singularity of Ambedkar’s perspective on, the uncompromisingly critical stance he adopts towards, and the sheer extent and earnestness of his engagement with, the Manusmṛti lends his treatment of this most authoritative of texts a topic worthy of closer attention not just from the burgeoning legion of scholars studying him but even from specialists of dharmaśāstra, especially in the light of recent interest in the political and social aspects of the origin and nature of this genre.
Symbolic and Non-Symbolic numbers differently affect center identification in a number-line bisection task
Authors: Porru Annamaria , Ronconi Lucia , Lucangeli Daniela , Regolin Lucia , Benavides-Varela Silvia , Rugani Rosa
Published: December 2024

Numerical and spatial representations are intertwined as in the Mental Number Line, where smaller numbers are on the left and larger numbers on the right. This relationship has been repeatedly demonstrated with various experimental approaches, such as the line bisection task.

Spatial accuracy appears to be systematically distorted leftward for smaller digits by elaboration of spatial codes during number processing. Other studies have investigated perceptual and visuo-spatial attention bias using the digit line bisection task, suggesting that these effects may be related to a cognitive illusion in which the reference numbers project their values onto the straight line, creating an illusory lateral disparity. On the other hand, both dot arrays (non-symbolic stimuli) and arabic numbers (symbolic stimuli) demonstrate a privileged relation between spatial and numerical elaboration. The bias toward the larger numerosity flanker was attributed to a length illusion. There is, however, no consensus regarding whether physical features and symbolic and non-symbolic numerical representations exert the same influence over spatial ones.

In the present study, we carried out a series of 4 Experiments to provide further evidence for a better understanding of the nature of this differential influence. All experiments presented the numbers in both symbolic and non-symbolic formats. In Experiment 1, the numbers “2-8” were presented in a variety of left-right orientations. In Experiment 2, the flankers were identical, “2-2” or “8-8”, and symmetrically displaced with respect to the line. In Experiment 3, we employed asymmetrically distributed eight dots, or font sizes in “8-8” numerals, to create a perceptual imbalance. In Experiment 4, we replicated the manipulation used in Experiment 3, but with two dots and “2-2” numerals.

The Non-Symbolic format induced stronger leftward biases, particularly when the larger numerosity (Experiment 1) or the denser stimuli near the line (Experiments 3 and 4) were on the left, while no bias emerged when flankers were numerically equivalent and symmetrical (Experiment 2). The left bias may result from a tendency to estimate the influence of stimulus perception associated with participant’ scanning direction, similar to the direction of pseudoneglect. Conversely, the Symbolic format induced mostly right bias, possibly due to left-lateralized processing and a tendency to use a common strategy involving scanning from left to right.

Altogether our data support the view that abstract numbers and non-symbolic magnitude affect perceptual and attentional biases, yet in distinctive ways.
Vibratory stimulation and not action observation or mirror therapy reduces paralyzed hand spasticity in chronic stroke survivors
Authors: Nakano Hideki , Nakagawa Kotaro , Ikuno Tatsuya , Nagashima Munenori , Naito Eiichi
Published: December 2024

Objective

Post-stroke spasticity prevalence increases with time from stroke onset, and negatively impacts the patient’s quality of life. Vibratory stimulation (VS) to the spastic muscles can reduce spasticity, whereas action observation (AO) and mirror therapy (MT) are reported to be less effective for spasticity reduction. However, these effects have not been compared within the same individuals. Therefore, this study compared the spasticity-reducing effects of VS, AO, and MT.

Methods

Independent groups of 13 patients with chronic stroke participated in the study. In Experiment 1, the participants underwent VS, AO, and combined VS+AO on separate days. In Experiment 2, different participants received VS, MT, and VS+MT. Spasticity was assessed using the Modified Ashworth Scale (MAS) before and after the interventions.

Results

In Experiment 1, VS significantly reduced MAS scores but not AO, and AO did not enhance the VS effect in combined therapy. In Experiment 2, VS significantly reduced the MAS scores, but not MT, and MT did not enhance the VS effect in combined therapy.

Conclusion

Spastic muscle VS reduced spasticity in chronically paralyzed hands; however, AO and MT did not enhance the VS effect. VS alone may be a more effective treatment for spasticity in patients with chronic stroke.
Willingness to pay for COVID-19 vaccine and its correlates: A cross-sectional survey in Bangladesh
Authors: Hossain Mohammad Bellal , Alam Md. Zakiul , Islam Md. Syful , Sultan Shafayat , Faysal Md. Mahir , Rima Sharmin , Hossain Md. Anwer , Mamun Abdullah Al , Mamun Abdullah-Al-
Published: December 2024

The Government of Bangladesh has offered COVID-19 vaccines at no cost; however, sustaining this free vaccination program for a large population poses significant challenges. Assessing willingness to pay (WTP) is essential for understanding potential pricing strategies, subsidy requirements, and vaccine demand. This study aimed to estimate the prevalence of WTP for COVID-19 vaccines and identify its influencing factors to support program sustainability. Using a cross-sectional design, data were collected from 1,497 respondents through online, and face-to-face interviews and multiple logistic regression was employed to analyze the correlates of WTP. Results showed that 50.9% of participants were willing to pay, with an average WTP of 754.55 BDT (US$8.93) and a median of 300 BDT (US$3.55). WTP was significantly higher among individuals with graduate (aOR=2.2, P=0.007) or Masters & MPhil/PhD education (aOR=2, P=0.030), higher family income (aOR=1, P=0.039), and those with more excellent knowledge about the vaccine (aOR=1.1, P=0.003), positive behavioral practices (aOR=1.1, P<0.001), stronger subjective norms (aOR=1.2, P=0.009), higher anticipated regret (aOR=1.2, P=0.005), and perceived benefits (aOR=1.1, P=0.029). Conversely, WTP was lower among participants with negative attitudes toward vaccines (aOR=0.9, P<0.001) and high behavioral control (aOR=0.9, P=0.006). With nearly half of respondents unwilling to pay, the study highlights the need to improve vaccine-related knowledge, promote positive behaviors, reduce vaccine hesitancy, and enhance income-based affordability to increase WTP. Health promotion efforts should focus on disseminating vaccine knowledge and addressing negative perceptions. Additionally, a subsidized program for low-income groups could help mitigate financial barriers and promote equitable vaccine access.
High-efficiency genomic mapping of chromatin-associated targets with CUT&RUN
Authors: Firestone Tessa M. , Venters Bryan J. , Novitzky Katherine , Albertorio-Sáez Liz Marie , Barnes Courtney A. , Fedder-Semmes Karlie N. , Hall Nathan W. , Hickman Allison R. , Kaderli Mark , Windham Carolina Lin , Marunde Matthew R. , Maryanski Danielle N. , Noll Kelsey , Shannon Leslie , Spengler Jennifer , Cowles Martis W. , Sun Zu-Wen , Keogh Michael-Christopher , Johnstone Andrea L. , Weinzapfel Ellen N. , Sun Lu
Published: December 2024

The precise regulation of chromatin composition is critical to gene expression and cellular identity, and thus a key component in development and disease. Robust assays to study chromatin features, including histone post-translational modifications (PTMs) and chromatin-associated proteins (e.g., transcription factors or PTM readers), are essential to understand their function and identify novel therapeutic strategies. To this end, Cleavage Under Targets and Release Using Nuclease (CUT&RUN) has emerged as a powerful tool for high-resolution epigenomic profiling. The approach has been successfully applied to numerous cell and tissue types, informing on target genomic distribution with unprecedented sensitivity and throughput. Here, we provide a detailed CUT&RUN protocol from sample collection through data analysis, including best practices and defined controls to ensure specific, efficient, and robust target profiling.
Neural Dynamics of Tonic Cold Pain: A Novel Investigation of an In-Scanner Alternative to the Cold Pressor Test in Healthy Individuals
Authors: Medina Sonia , Hughes Sam W.
Published: December 2024

The cold pressor task (CPT) is widely used to study tonic pain during acute and chronic conditions and is often as used as a conditioning stimulus to activate descending pain control systems. However, logistical challenges in magnetic resonance imaging (MRI) limit its application, hindering the understanding of CPT’s neural dynamics. To address this, we acquired resting-state functional MRI data from 30 healthy participants before, during, and after immersion in gelled-cold water, the closest in-scanner alternative to date to CPT for prolonged stimulation. Participants provided subjective pain intensity ratings after each scan, as well as average pain perceived during noxious stimulation, using a numeric rating scale (NRS). Following fMRI, participants rated their pain continuously during identical tonic noxious stimulation of the contralateral hand using a visual analogue scale (VAS). We employed three complementary methods to examine changes in brain function across fMRI conditions: a data-driven approach via independent component analysis (ICA), seed-to-whole-brain connectivity analysis with the periaqueductal grey (PAG) as seed, and spectral dynamic causal modelling (spDCM) to explore effective connectivity changes across the dorsal anterior cingulate cortex (dACC), anterior insulae (AI), thalamus, and PAG. NRS scores were significantly higher following tonic cold compared to baseline and recovery conditions. Continuous VAS reflected sustained mild-to-moderate pain over six minutes, with average VAS scores not significantly differing from NRS ratings recorded in the scanner. ICA identified engagement of descending pain control and sensorimotor networks during pain, with the latter persisting during recovery. Seed-based analysis revealed a disengagement between the PAG and cortical/subcortical regions involved in pain processing, such as the dACC, midcingulate cortex, AI, intraparietal sulcus, and precuneus. Finally, spDCM revealed tonic pain neural signature was most likely characterised by top-down inhibitory and bottom-up excitatory connections. This study establishes the cold gelled-water paradigm as a robust in-scanner alternative to CPT. By uncovering key neural dynamics of CPT, we provide new insights into the brain and brainstem mechanisms of tonic cold pain paradigms routinely used in psychophysical pain studies.

Key points

Immersion in gelled-cold water is a reliable in-scanner substitute for the cold pressor task, enabling prolonged tonic cold pain research in MRI.

Key neural dynamics, such as PAG-driven excitatory inputs and AI-mediated inhibitory control, were identified, providing new insights into cold pain modulation.

By taking a multi-method approach, including ICA, seed-based connectivity, and DCM, we offer a comprehensive view of the neural networks involved in tonic cold pain, bridging neuroimaging and behavioural research.
Leukaemia cell intrinsic and extrinsic factors cooperate to facilitate the survival and proliferation of KMT2A-rearranged B-ALL in the CNS niche.
Authors: Duguid Alasdair , Malouf Camille , Nitsche Leslie , Barrett Neil , Smith Owen , Halsey Chris , Ottersbach Katrin
Published: December 2024

Infant B-cell acute lymphoblastic leukaemia (B-ALL) is a rare, aggressive entity characterised by KMT2A rearrangements and poor outcomes. One of the unique features of KMT2A-rearranged infant ALL that contributes to these poor outcomes is a particularly high rate of central nervous system (CNS) involvement. There is a broad lack of understanding regarding the molecular processes and immune environment in CNS ALL. This hinders the development of targeted therapies for CNS ALL, which is increasingly essential given the potentially reduced efficacy of current immunotherapies in this specialised environment. In this study, we used an immune-competent KMT2A-AFF1+ infant B-ALL murine model to explore the cell-intrinsic and cell-extrinsic mechanisms that underpin this clinically significant complication. We show novel functional impacts on leukaemia propagating cells following exposure to the CNS niche which results in unique leukaemia repopulation dynamics. Transcriptomic and immune cell profiling by niche showed differences in the immune microenvironment between the CNS and bone marrow niches. The CNS niche demonstrates supressed T cell and macrophage activity which may be part of a wider CNS niche-specific immune escape mechanism. Our transcriptomic comparisons by niche also led us to explore the role of PI3K pathway activation in the propagation of leukaemia cells within the CNS niche. We identify miR-93 as a possible master regulator of this process. The importance of miR-93 is emphasised as it is shown to be upregulated in CNS leukaemia cells across multiple murine KMT2A-AFF1 B-ALL model systems and in primary KMT2A-AFF1 B-ALL patient samples. We conclude by showing impaired CNS engraftment of leukaemia cells upon miR-93 knockdown, cementing its importance in CNS leukaemia biology and opening up new CNS-specific therapeutic opportunities.
Spatial and feature-selective attention interact to drive selective coding in frontoparietal cortex
Authors: Dermody Nadene , Lorenz Romy , Goddard Erin , Villringer Arno , Woolgar Alexandra
Published: December 2024

Attention enables the selective processing of relevant information. Two types of selective attention, spatial and feature attention, have separable neural effects but in real life are often used together. Here, we asked how these types of attention interact to affect information coding in a frontoparietal ‘multiple-demand’ (MD) network, essential for attentional control. Using functional magnetic resonance imaging (fMRI) with multivariate pattern analysis, we examined how covert attention to object features (colour or shape) and spatial locations (left or right) influences coding of task-related stimulus information. We found that spatial and feature attention interacted multiplicatively on information coding in MD and visual regions, such that there was above-chance decoding of the attended feature of the attended object and no detectable coding of visually equivalent but behaviourally irrelevant aspects of the visual display. The attended information had a multidimensional neural representation, with stimulus information (e.g., colour) and discrimination difficulty (distance from the categorical decision boundary) reflected in separate dimensions. Rather than boosting processing of whole objects or relevant features across space, our results suggest neural activity reflects precise tuning to relevant information, indicating a highly selective control process that codes behaviourally relevant information across multiple dimensions.
Developmental programmes drive cellular plasticity, disease progression and therapy resistance in lung adenocarcinoma
Authors: Bienkowska Kamila J , Gallardo Y Stephany , Zainal Nur S , Ellis Matthew , Lopez Maria-Antoinette , Austine Judith , Pittla Sai , Chee Serena J , Alzetani Aiman , Shaw Emily C , Ottensmeier Christian H , Thomas Gareth J , Hanley Christopher J
Published: December 2024

Background

Cellular plasticity, involving loss of lineage determination and emergence of hybrid cell states, plays a pivotal role in non-small cell lung cancer (NSCLC) disease progression and therapy resistance. However, the full spectrum of atypical states generated in human NSCLC and the pathways that regulate them are yet to be fully elucidated. Here we examine the role of developmental programmes, alveogenesis and branching morphogenesis (BM), in regulating phenotypic diversity in NSCLC.

Methods

Transcriptomic analysis of epithelial cells isolated from murine lungs at different stages of organogenesis were used to derive gene signatures for developmental programmes. Bulk tissue transcriptomic datasets from human NSCLC and non-neoplastic control samples were used to identify whether developmental programmes were associated with molecular, morphological, and clinical parameters. Single-cell RNA-sequencing was used to identify malignant cell states in human NSCLC (n = 16,621 epithelial cells from 72 samples) and protein level validation of these states was carried out using multiplexed immunohistochemistry (n = 40).

Results

Mutually antagonistic regulation of alveogenesis and BM was found to account for a significant proportion of transcriptomic variance in human NSCLC bulk tissue datasets. BM activation was associated with poor overall survival rates in five independent lung adenocarcinoma (LUAD) cohorts (p=2.04e-13); and was significantly prognostic for resistance to tyrosine kinase inhibitors (TKIs; p=0.003) and immune checkpoint blockade (ICBs; p=0.014), in pre-treatment biopsies. Single-cell RNA-sequencing analysis revealed that malignant LUAD cells with loss of alveolar lineage fidelity predominantly acquired inflamed or basal-like cellular states, which were variably persistent in samples from TKI and ICB recurrence.

Conclusions

Our results show LUAD tumours undergo reversion from an alveogenic to branching morphogenic phenotype during disease progression, generating inflamed or basal-like cell states that are variably persistent following TKI or ICB treatments. These findings identify prognostic biomarkers for therapy response and underscore the role of different cell states in resistance to multiple treatment modalities.
Stranded short nascent strand sequencing reveals the topology of eukaryotic DNA replication origins inTrypanosoma brucei
Authors: Stanojcic Slavica , Barckmann Bridlin , Monsieurs Pieter , Crobu Lucien , George Simon , Sterkers Yvon
Published: December 2024

The structure of eukaryotic origins is a long-standing question in the DNA replication field, and the universal features that define the genomic regions acting as replication starting sites remain unclear. In this study, we employed the stranded SNS-seq methodology, a high-throughput sequencing method that preserves the directionality of short nascent strands, to map a set of origins inTrypanosoma brucei. This approach enhanced the specificity and resolution of origin mapping. Our findings indicated that replication predominantly initiates in intergenic regions, situated between poly(dA) and poly(dT) enriched sequences. Experimentally detected G4 structures were observed in the vicinity of some origins. These structures were observed to be embedded within poly(dA) enriched sequences in a strand-specific manner, with the G4s on the plus strand located upstream and the G4s on the minus strand located downstream of the centre. The centre of origin was mainly characterised by low nucleosome occupancy, with flanking regions displaying high nucleosome occupancy. Additionally, our findings revealed that 90% of origins overlapped with previously reported R-loops. To gain further insight, DNA combing analysis was employed to compare replication at the single-cell level with that observed at the entire cell population level. Finally, a model of eukaryotic origin has been proposed.

GRAPHICAL ABSTRACT
Cognitive Screening Tools for Dementia Detection in Primary Healthcare Centres in India: A Scoping Review
Authors: Jeevitha Gowda R
Published: December 2024

Background

Dementia is a growing public health concern in India, with an increasing prevalence among the elderly population. Early detection is crucial for effective intervention. Primary healthcare (PHC) centres play a vital role in identifying cognitive impairment; however, the effectiveness of cognitive screening tools in these settings is questionable.

Objective

This scoping review explores the cognitive screening tools available for dementia detection in PHC centres in India, assesses their effectiveness, and identifies the need for their improvement and adaptation.

Methods

A systematic search was conducted in PubMed, Scopus, and Google Scholar for studies published up to October 2024. A total of 29 studies were identified, indicating that tools such as the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are frequently used. However, these tools face significant challenges related to educational background and language comprehension, impacting their effectiveness.

Conclusion

There is an urgent need for culturally and linguistically appropriate cognitive screening tools in PHC settings in India to enhance the early detection of dementia.
Structural, Behavioral, and Symptomatic Predictors of Risk Allele Frequency at rs10866912
Authors: Forthman Katherine L. , Periyasamy Sathish , Kuplicki Rayus , Paulus Martin P. , Mowry Bryan J.
Published: December 2024

This study examines the distribution of risk (A) alleles at rs10866912 among 480 individuals stratified by group assignment, gender, age, race/ethnicity, body mass index (BMI), and education level. Preliminary analysis indicated higher prevalence of the risk allele in the population diagnosed with a psychiatric disorder, in concordance with past research. Linear models were applied to elucidate the relationship between the risk allele and various measures covering drug use, diet, psychiatric symptoms, neuropsychiatric ability, and structural brain measures. The findings highlight significant variations in allele frequencies across these measures, in particular egg consumption and analgesic use, which may provide insights into the mechanisms by which this genetic marker influences development of psychiatric disorders.
Underdiagnosis of myalgic encephalomyelitis/chronic fatigue syndrome-like illness in a large integrated healthcare system — Kaiser Permanente Northern California, 2022-2023
Authors: Wood Mariah S. , Halmer Nicole , Bertolli Jeanne , Amsden Laura B. , Nugent Joshua R. , Lin Jin-Mann S. , Rothrock Gretchen , Nadle Joelle , Chai Shua J. , Champsi Jamila H. , Yang James , Unger Elizabeth R. , Skarbinski Jacek ,   STOP-ME/CFS and COVID-SELECT
Published: December 2024

Background

Surveillance of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a chronic, debilitating multisystem illness, is challenging because ME/CFS can be under-recognized in healthcare settings.

Methods

Using a population-based panel study of 9,820 adult members of Kaiser Permanente Northern California (KPNC), a large, integrated healthcare system, we compared survey-defined ME/CFS-like illness with presence of an ME/CFS diagnosis in the electronic health record (EHR) to evaluate ME/CFS underdiagnosis.

Results

Of those with survey-defined ME/CFS-like illness, an estimated 97.8% (95% confidence interval [CI] 97.1%-98.4%) did not have an ME/CFS diagnosis in the EHR. The group without EHR diagnosis was younger, less likely to identify as white non-Hispanic, and more likely to have developed fatigue in the past three years than the EHR diagnosed group. Both diagnosed and undiagnosed ME/CFS-like illness groups had significantly impaired physical, cognitive, and social functioning, and significantly worse mental health and anxiety than those without ME/CFS-like illness.

Conclusion

ME/CFS is underdiagnosed in the Kaiser Permanente Northern California healthcare system. Enhanced syndromic surveillance that characterizes patients with ME/CFS who have not been diagnosed has the potential to increase timely recognition of ME/CFS.
Efficacy and Safety of Atorvastatin as Adjunctive Treatment in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis
Authors: Chen Ke , Xu Bowen , Zhang Lu , Fang Li , Wu Di , Ding Huanzhang , Li Zegeng
Published: December 2024

Background

Accumulating evidence suggests that atorvastatin, a widely used lipid-lowering agent, may provide additional benefits for chronic obstructive pulmonary disease (COPD) patients, including anti-inflammatory effects and improved lung function. However, inconsistent findings across studies warrant a systematic evaluation to clarify its clinical role.

Objective

To systematically evaluate the efficacy and safety of atorvastatin as an adjunctive treatment for COPD and inform clinical decision-making.

Methods

A comprehensive search of PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, WanFang, CBM, and VIP databases identified randomized controlled trials (RCTs) up to May 20, 2024. Meta-analysis using RevMan 5.3 and R software was performed to estimate pooled effects with mean differences or standardized mean differences (95% CI). Subgroup analyses explored variations by treatment duration and dosage.

Results

Twenty-four RCTs involving 2,534 patients demonstrated significant benefits of atorvastatin for stable COPD and acute exacerbations (AECOPD):Lung function: FEV1%pred increased by 5.36% (95% CI: 4.57–6.14), FEV1/FVC by 6.30% (95% CI: 4.46–8.14), and FEV1 by 0.21 L (95% CI: 0.15–0.27).Inflammatory markers: CRP decreased by 1.87 mg/L (95% CI: 1.45–2.29), with reductions in hs-CRP and IL-6.Quality of life: CAT scores improved by 3.5 points (95% CI: 2.8–4.2).Exercise capacity: The 6-minute walk distance increased by 25.4 meters (95% CI: 18.1– 32.7).Stronger evidence emerged with 3-month treatments (I² < 30%) and consistent benefits at 20 mg doses. Adverse events were mild and self-limiting.

Conclusion

Atorvastatin (20 mg) significantly improves lung function, reduces inflammation, and enhances quality of life in COPD patients, with a favorable safety profile. Although not currently recommended in COPD guidelines, these findings support further trials to validate its potential role in COPD management.
Development of a novel transcriptomic measure of aging: Transcriptomic Mortality-risk Age (TraMA)
Authors: Klopack Eric T. , Seshadri Gokul , Arpawong Thalida Em , Cole Steve , Thyagarajan Bharat , Crimmins Eileen M.
Published: December 2024

Increasingly, research suggests that aging is a coordinated multi-system decline in functioning that occurs at multiple biological levels. We developed and validated a transcriptomic (RNA-based) aging measure we call Transcriptomic Mortality-risk Age (TraMA) using RNA-seq data from the 2016 Health and Retirement Study using elastic net Cox regression analyses to predict 4-year mortality hazard. In a holdout test sample, TraMA was associated with earlier mortality, more chronic conditions, poorer cognitive functioning, and more limitations in activities of daily living. TraMA was also externally validated in the Long Life Family Study and several publicly available datasets. Results suggest that TraMA is a robust, portable RNAseq-based aging measure that is comparable, but independent from past biological aging measures (e.g., GrimAge). TraMA is likely to be of particular value to researchers interested in understanding the biological processes underlying health and aging, and for social, psychological, epidemiological, and demographic studies of health and aging.
Reporting quality of quantitative polymerase chain reaction (qPCR) methods in scientific publications
Authors: Drude Natascha , Baselly Camila , Gazda Małgorzata Anna , May Jan-Niklas , Tienken Lena , Abbasi Parya , Weissgerber Tracey , Burgess Steven
Published: December 2024

Reproducibility is a significant concern in scientific research and complex methods like quantitative polymerase chain reaction (qPCR) demand stringent reporting standards to ensure that the methods are reproducible, data are sound, and conclusions are trustworthy. Although the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines were introduced in 2009 to improve qPCR reporting, a 2013 study identified ongoing deficiencies that hinder reproducibility. To further investigate the transparency and completeness of qPCR reporting, we systematically assessed articles published in the top 20 journals in genetics and heredity (n=186) and plant sciences (n=246) that used qPCR. Our analysis revealed frequent omissions and inadequate specification of critical information necessary for evaluating and replicating qPCR experiments. RNA integrity, along with assessment methods and instruments used to assess it, are seldom reported. Although primer sequences are often disclosed, names and accession numbers of housekeeping genes are frequently omitted. Additionally, essential details about RNA extraction, RNA-to-cDNA conversion, and qPCR, such as kit names, catalog numbers, and reagent information, are often missing. Our findings underscore the urgent need for improved reporting practices in qPCR experiments, emphasizing quality controls, detailed descriptions of reagents and materials, and greater analytical transparency. Addressing these reporting deficiencies is crucial for enhancing the reproducibility and evaluating the trustworthiness of qPCR research. Potential solutions include encouraging authors to cite protocols published in online repositories, providing reporting templates, or developing automated tools to check reporting compliance.
Lesions of anterior cingulate cortex disrupt an electrophysiological signature of reward processing in humans
Authors: Oerlemans Joyce , Alejandro Ricardo J. , Hemelsoet Dimitri , Genbrugge Eva , Bouche Katie , Defreyne Luc , De Herdt Veerle , Holroyd Clay B.
Published: December 2024

The reward positivity (RewP) is an event-related brain potential (ERP) component associated with feedback and reward processing. Although the component is said to be generated in anterior cingulate cortex (ACC), this inference is disputed because of the inverse problem. Recently, by conducting a current source density analysis of intracranial electroencephalogram (EEG) data recorded from a large cohort of epilepsy patients, we provided direct evidence that the RewP is produced by a circumscribed region in caudal ACC corresponding to Brodmann areas 24c’ and 32’. In the present study we confirm that this brain area is the source of the RewP by examining the effects of damage to frontal cortex on RewP amplitude. We recorded scalp EEG from 68 stroke patients with damage to frontal cortex while they engaged in a trial-and-error guessing task used to elicit a canonical RewP. Application of non-parametric voxel-based lesion-symptom mapping to the lesion data revealed that damage to Brodmann areas 24c’ and 32’ attenuated RewP amplitude, whereas damage to other parts of frontal cortex did not affect it. These results provide causal evidence that the caudal ACC generates the RewP and underscore the contribution of this brain region toward motivating extended behaviours.

Significance statement

The reward positivity (RewP) is an event-related brain potential component that reflects reward processing in the brain. Although multiple studies have suggested that anterior cingulate cortex (ACC) is the neural generator of the RewP, this assertion is disputed mainly because of the inverse problem. In this study, we present direct evidence that the RewP is generated in caudal ACC by performing voxel-based lesion-symptom mapping (VLSM) in a cohort of 68 stroke patients with lesions in the frontal lobe. We found that a circumscribed region in right caudal ACC was significantly associated with a reduced RewP, providing the first causal evidence that this region generates the RewP in humans. These fundings elucidate the central role ACC plays in motivating extended behaviours.