bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure to the Indian Ocean Tsunami shapes the HPA-axis resulting in HPA “burnout” 14 years later
Authors: Lawton Ralph , Frankenberg Elizabeth , Seeman Teresa , Crimmins Eileen , Sumantri Cecep , Thomas Duncan
Published: October 2023

Despite significant research on the effects of stress on the hypothalamic–pituitary–adrenal (HPA) axis, questions remain regarding long-term impacts of large-scale stressors. Leveraging data on exposure to an unanticipated major natural disaster, the 2004 Indian Ocean tsunami, we provide causal evidence of its imprint on hair cortisol levels fourteen years later. Data are drawn from the Study of the Tsunami Aftermath and Recovery, a population-representative longitudinal study of tsunami survivors who were living along the coast of Aceh, Indonesia, when the tsunami hit. Annual rounds of data, collected before, the year after and 2 y after the disaster provide detailed information about tsunami exposures and self-reported symptoms of post-traumatic stress. Hair samples collected 14 y after the tsunami from a sample of adult participants provide measures of cortisol levels, integrated over several months. Hair cortisol concentrations are substantially and significantly lower among females who were living, at the time of the tsunami, in communities directly damaged by the tsunami, in comparison with similar females living in other, nearby communities. Differences among males are small and not significant. Cortisol concentrations are lowest among those females living in damaged communities who reported elevated post-traumatic stress symptoms persistently for two years after the tsunami, indicating that the negative effects of exposure were largest for them. Low cortisol is also associated with contemporaneous reports of poor self-rated general and psychosocial health. Taken together, the evidence points to dysregulation in the HPA axis and “burnout” among these females fourteen years after exposure to the disaster.
Evidence for lung barrier regeneration by differentiation prior to binucleated and stem cell division
Authors: Guild Joshua , Juul Nicholas H. , Andalon Andres , Taenaka Hiroki , Coffey Robert J. , Matthay Michael A. , Desai Tushar J.
Published: October 2023

With each breath, oxygen diffuses across remarkably thin alveolar type I (AT1) cells into underlying capillaries. Interspersed cuboidal AT2 cells produce surfactant and act as stem cells. Even transient disruption of this delicate barrier can promote capillary leak. Here, we selectively ablated AT1 cells, which uncovered rapid AT2 cell flattening with near-continuous barrier preservation, culminating in AT1 differentiation. Proliferation subsequently restored depleted AT2 cells in two phases, mitosis of binucleated AT2 cells followed by replication of mononucleated AT2 cells. M phase entry of binucleated and S phase entry of mononucleated cells were both triggered by AT1-produced hbEGF signaling via EGFR to Wnt-active AT2 cells. Repeated AT1 cell killing elicited exuberant AT2 proliferation, generating aberrant daughter cells that ceased surfactant function yet failed to achieve AT1 differentiation. This hyperplasia eventually resolved, yielding normal-appearing alveoli. Overall, this specialized regenerative program confers a delicate simple epithelium with functional resiliency on par with the physical durability of thicker, pseudostratified, or stratified epithelia.
Monocular vision-based online kinematic calibration method for five-axis motion platform
Authors: Tang Xianxing , Zhou Haibo , Jiang Xuening
Published: October 2023

This article proposes an online kinematic calibration method for simultaneous five-axis motion for solving the problems of low kinematics accuracy and a highly complex kinematic calibration of the five-axis motion platform. First, the ArUco markers are used in a vision system for large stroke detection, while kinematics models of the five-axis motion platform are established based on the screw theory. This article proposes an online kinematic parameter identification method for simultaneous motion along five axes, using a monocular camera as a measurement tool. Furthermore, the stability and effectiveness of the identification algorithm are verified by simulation and experiment. Specifically, a process trajectory commonly used to conduct experiments verifies the scheme’s influence on the kinematic accuracy. Experimental results show that the proposed kinematic calibration method reduces the average position error of the five-axis motion platform by 88.59% and the average direction error by 84.54%, thus proving that the proposed kinematic calibration method can significantly improve the kinematic accuracy of the five-axis motion platform and verifying the applicability and effectiveness of the proposed scheme.
A multi-model method for tool wear prediction with deep temporal features and correlation alignment
Authors: Dong Jingchuan , Chen Tao , Gao Yubo , Su Depeng , Jiang Hongyu
Published: October 2023

Accurate prediction of tool wear is essential to ensure the machining quality of parts. However, in the actual milling process, the data distribution varies greatly between sensor signals due to variations in individual tools and machining parameters; moreover, a single deep learning model is less reliable when processing a large volume of signals. All these problems make accurate tool wear prediction challenging. Therefore, we propose a multi-model method with two-stage. In the first stage, the tool wear data is initially divided into two parts. For each part, we design a correlation-aligned multiscale convolutional temporal attention gated recurrent neural network model to perform preliminary prediction, aiming at extracting the deep temporal features from diverse signals and mitigating the sensitivity of the features to the changes in data distributions. In the second stage, we adaptively aggregate the preliminary prediction from multiple models to obtain the final prediction via a joint decision-making module to extend the decision boundary of single model and improve the tool wear prediction performance. Finally, two sets of experiments are conducted for different tools and machining conditions. The experimental results show that our proposed method significantly reduces the root mean square error (RMSE) by 15% and the mean absolute error by 18% compared to other methods.
The role of recombination in constriction of a positive column of a glow discharge in inert gases
Authors: Siasko A V , Karasev V Yu , Golubovskii Yu B
Published: October 2023

The work is aimed at the experimental determination of the role of volume recombination in a positive column of a DC discharge in helium during the transition from a diffuse homogeneous state to a constricted stratified regime under real discharge conditions of high electron and gas temperatures (

T
e

≈
2

eV,

T
g

>
1000

 K). The investigation is based on the probe measurements of the wall current determined by the flux of charged particles towards the boundary of a cylindrical discharge tube. The experiments were carried out in helium, neon, and argon in the range of reduced pressures 1.2–300 Torr·cm. In heavy inert gases, the transition to a constricted regime is determined by the active loss of charged particles in the volume. In contrast to neon and argon, experiments in helium demonstrated that the role of volume recombination is insignificant during the transition to a constricted regime. The rate of volume losses in helium in real conditions is very low compared to neon and argon. The obtained results allow one to calculate the volume recombination rate by comparing the experimentally measured wall currents with the corresponding numerical calculations within the collision-radiative model.
Analysis of energy conversion capability among various magnetostrictive materials for energy harvesting
Authors: Liu Yuanyuan , Lallart Mickael , Ducharne Benjamin , Makihara Kanjuro , Sebald Gael
Published: October 2023

This work addresses vibrational energy harvesting using magnetostrictive materials. In this field, materials with exceptional magneto-mechanical coupling properties (e.g. Galfenol, Terfenol-D) have attracted significant attention. Only a few magnetostrictive materials have been tested in devices, however, leaving the actual influence of these materials’ properties on the energy harvesting device open to question. This work compares an extensive range of ferromagnetic materials through analysis of their magnetic behavior under static stress. To enable fair comparison of the materials, a model was developed to interpolate their magnetic anhysteretic curves under fixed stress of σ = ±50 MPa. The energy harvesting process was then simulated using a theoretical Ericsson thermodynamic cycle, where the area represents the energy density. This approach estimates the ultimate energy density of the materials using a fair approach, without placing conditions on the applied magnetic field. The correlation between ultimate energy density and the magnetoelastic coefficient show that highly magnetostrictive materials achieve higher ultimate energy densities, as expected. In the low field range, it is however concluded that all materials exhibit energy densities of the same order of magnitude. Secondly, the magnetoelastic coefficient versus excitation field characteristics revealed an optimal bias magnetic field for each material. Finally, for realistic implementation, the paper considers a pre-stress in combination with a bias magnetic field and the small dynamic variations that result from currents induced in surrounding coils. A model was developed and revealed an optimum output energy density that was independent of the geometry and the coil. An energy harvesting figure of merit was then defined to enable a final comparison of the materials, encompassing both material characteristics and realistic applications. Under these working conditions and with all costs considered, some low-magnetostriction materials appeared able to compete with giant magnetostriction materials.
Elastic metamaterials for guided waves: from fundamentals to applications
Authors: Lee Jeseung , Kim Yoon Young
Published: October 2023

Guided waves, elastic waves propagating through bounded structures, play a pivotal role in various applications, including ultrasonic non-destructive testing and structural health monitoring. Recently, elastic metamaterials artificially engineered to exhibit physical properties not typically seen in nature have emerged as a ground-breaking approach, heralding a new era in guided wave-based technologies. These metamaterials offer innovative solutions to overcome the inherent constraints of traditional guided wave-based technology. This paper comprehensively reviews elastic metamaterials from their fundamental principles to diverse applications, focusing on their transformative impact in guided wave manipulation.
Mathematical modelling and experimental study of a novel planar micro-positioning stage using shape memory alloy actuators
Authors: Rahbari Hossein , Fathi Alireza , Dardel Morteza
Published: October 2023

The application of smart materials as actuators in precise positioning systems has witnessed significant growth in recent years. However, the use of shape memory alloy (SMA) materials in this context is hindered by their slow response and complex nonlinear behaviour. To overcome these limitations, this paper introduces a novel approach that incorporates two opposite SMA actuators into a flexure hinge type micro-positioning stage, aiming to enhance the system speed. A semi-analytical modelling approach is employed to model the nonlinear behaviour of the SMA actuator. Using the available material models for SMA materials and the nonlinear curved beam theory, the governing equations of the proposed SMA actuator are derived and the resulted partial differential equations are reduced to an algebraic equation based on the Galerkin method. The resulting equations are then solved using the return map method. To validate the accuracy and effectiveness of the proposed model, an experimental setup is constructed. The experimental results demonstrate the model ability to accurately predict the behaviour of the system. Additionally, the developed model allows for the extraction of stress and strain profiles of the SMA actuators for designing the actuator. The study highlights the potential of integrating the proposed model with robust control methods for future works, aiming to effectively control micro-positioning systems and further enhance their performance.
3D numerical investigation on delamination behavior of the epoxy impregnated REBCO pancake coil
Authors: Shen Yansong , Chen Zhidong , Peng Xubin , Wei Yunpeng
Published: October 2023

Superconducting coils made of rare-earth-barium-copper-oxide (REBCO) coated conductor (CC) exhibit superior electromagnetic performance. Employing epoxy impregnation can improve the structural integrity and mechanical property of the superconducting coils. However, due to the extreme work environment and weak adhesion strength of REBCO CC, the delamination induced by radial thermal stress and electromagnetic force significantly affects the electromagnetic property and the reliability of the superconducting coil. This study proposes a three-dimensional thermal-electromagnetic mechanical delamination model that incorporates the cohesive zone model to investigate the delamination mechanisms in epoxy impregnated REBCO pancake coils during the cooling and coil operation processes. The simulation employs a three-parameter Weibull distribution to account for the inhomogeneity of transverse tensile strength in the CCs. The delamination behavior and mechanisms of the coils under different conditions are analyzed. The simulation results show that the model considering random adhesion strength proves to be more effective in representing the delamination behavior of the coil. And large tensile radial stresses caused by thermal stresses and electromagnetic forces lead to the delamination behavior of the coil during cooling and operation. The main reason for the tensile radial stress is the mismatch in the thermal contraction among components of the coils during cooling process. Furthermore, we investigate the influence of the thermal expansion coefficient (CTE) and thickness of the mandrel, the CTE and prestress of the overband and the initial localized damage. The results indicate that these factors significantly affect the tensile radial stress and the extent of delamination in the windings. And the extent and distribution of delamination is related to the stress release caused by delamination to a certain degree.
Generation of ultra-long optical needles with dual-ring cosine filter
Authors: Zhang Yang , Wu Wenzhi , Lan Guoqiang , Chai Zhijun , Kong Degui
Published: October 2023

Combining the advantages of phase and amplitude modulation, we designed a dual-ring cosine filter which was consisted by an inner and outer ring, and the two rings have different number of paired cosine phase. Using the dual-ring cosine filter, ultra-long longitudinally polarized optical needles were obtained by tight focusing radially polarized Bessel-Gaussian beams with a single lens system. The obtained optical needles have a depth of focus of 268λ, lateral full width of 0.37λ at half height, the beam quality of 94%, and axial uniformity of 95%. In addition, we found that the depth of focus of obtained optical needles can be further stretched and the lateral dimension can be further compressed by increasing the number of paired cosine phase. The ultra-long optical needles were appropriately applied in the fields of optical beam lithography, laser direct writing, particle acceleration, and optical trapping.
2D acoustofluidic distributions in micro-chambers modulated by Sierpiński-type structural plates
Authors: Huang Huiyu , Chen Hao , Li Chen , Liu Pengzhan , Su Songfei , Weng Ruiting , Tang Qiang
Published: October 2023

In this study, a series of Sierpiński-type structural plates have been artificially introduced to generate diversified acoustofluidic distributions in the originally-static microfluidic chambers, which are stimulated under the oscillation of incident acoustic waves at different input frequency points. The complicated interactions between quasi/pseudo-Sierpiński-carpet shaped structural plates and incident ultrasonic waves, including acoustic reflection and diffraction, can initiate sophisticated spatio-temporal discrepancies along the sound propagation path and induce heterogeneous acoustic streaming vortices. In comparison with the existing construction strategies of microfluidic lab-on-a-chip devices, the introduction of fractalized elements like quasi/pseudo-Sierpiński-carpet shaped structural components can provide remarkable insights and expand application scenarios of unconventional acoustofluidic approaches, which is conducive to driving ultrasonic micro/nano manipulation technology from monotonousness to diversification. The preliminary research demonstrates the feasibility of considering Sierpiński-type structural features as tunable ingredients to customize acoustofluidic apparatuses for the exploration of topographical manipulation of micro/nano-scale particles and orientational operation of biological specimens.
Exact solutions and bifurcations of the time-fractional coupled Boussinesq-Burgers equation
Authors: Liu Minyuan , Xu Hui , Wang Zenggui
Published: October 2023

In this paper, the time-fractional coupled Boussinesq-Burgers equations are studied to construct exact solutions by utilizing the modified extended tanh-function method, the improved

(
G
′

/

G
)

method, the two variables

(
G
′

/

G
,
1

/

G
)

-expansion method and bifurcation analysis. Firstly, based on the modified Riemann-Liouville derivative and traveling wave transformation, the equations are rewritten as an ordinary differential equation. Some exact solutions, including singular, periodic, kink, anti-kink, soliton and periodic-singular solutions, are derived. Then, we graphically describe the 3D, density plots and solution profiles of some solutions by setting suitable parameters. Finally, the effectiveness of the methods applied is verified via bifurcation theory.
Non-thermal Higgs spectrum in reheating epoch: primordial condensate vs. stochastic fluctuation
Authors: Kaneta Kunio , Oda Kin-ya
Published: October 2023

Since electroweak symmetry is generally broken during inflation, the Standard Model Higgs field can become supermassive even after the end of inflation.
In this paper, we study the non-thermal phase space distribution of the Higgs field during reheating, focusing in particular on two different contributions: primordial condensate and stochastic fluctuations.
We obtain their analytic formulae, which agree with the previous numerical result.
As a possible consequence of the non-thermal Higgs spectrum, we discuss perturbative Higgs decay during reheating for the case it is kinematically allowed.
We find that the soft-relativistic and hard spectra are dominant in the decay rate of the stochastic fluctuation and that the primordial condensate and stochastic fluctuations decay almost at the same time.
Analysis of the stability region of light bullets propagating in the tunnel ionization mode in dielectric
Authors: Bugay Aleksandr N , Khalyapin Vyacheslav A
Published: October 2023

An analytical estimation of the parameters of light bullets formed in the region of anomalous group dispersion in dielectrics under conditions of tunneling photoionization has been carried out. A system of ordinary differential equations for the parameters of a laser pulse is obtained by the method of moments. A new analytical approximation is proposed for calculating the contribution of tunneling ionization. With the help of Lyapunov’s stability theory, a quasi-stationary solution of this system and conditions for a quasi-stable propagation regime are found.
Online bunch-by-bunch position monitoring and analysis at the Taiwan Photon Source
Authors: Huang C.-H. , Hsu K.-T. , Chen J. , Hu K.-H.
Published: October 2023

The online bunch-by-bunch position monitor has been
established through the utilization of a high-speed
analog-to-digital converter, synchronized meticulously with the
accelerator's radio frequency. This implementation serves the
purpose of refining the alignment of the four injection kickers. A
substantial volume of data needs to be managed when dealing with the
motion of the bunches. To untangle the intricacies of bunch motion,
an independent component analysis has been employed. This method
efficiently segregates the bunch motion into discrete sources. The
resulting bunch motion is a direct outcome of the linear combination
of these distinct sources. Consequently, this approach significantly
simplifies the overarching data analysis procedure. Throughout the
injection phase, the predominant factors influencing the oscillation
of filled bunches originate from three distinct sources. Firstly,
there is a contribution arising from the mismatch among the four
kickers during their activation period. Additionally, the damped
betatron oscillation and the oscillation generated by wake fields
constitute the other sources of bunch motion. To comprehend the tune
variation in these sources, an examination is conducted through a
numerical analysis of fundamental frequencies. Specifically, the
tune associated with the betatron oscillation is contingent upon the
amplitude of said oscillation. In contrast, the tune corresponding
to the wake-field oscillation displays comparably minor fluctuations
during both the growing and damping phases.
Gaps labeling theorem for the bubble-diamond self-similar graphs
Authors: Melville Elizabeth , Mograby Gamal , Nagabandi Nikhil , Rogers Luke G , Teplyaev Alexander
Published: October 2023

Motivated by the appearance of fractals in several areas of physics, especially in solid state physics and the physics of aperiodic order, and in other sciences, including the quantum information theory, we present a detailed spectral analysis for a new class of fractal-type diamond graphs, referred to as bubble-diamond graphs, and provide a gap-labeling theorem in the sense of Bellissard for the corresponding probabilistic graph Laplacians using the technique of spectral decimation. Labeling the gaps in the Cantor set by the normalized eigenvalue counting function, also known as the integrated density of states, we describe the gap labels as orbits of a second dynamical system that reflects the branching parameter of the bubble construction and the decimation structure. The spectrum of the natural Laplacian on limit graphs is shown generically to be pure point supported on a Cantor set, though one particular graph has a mixture of pure point and singularly continuous components.
Boundary-induced singularity in strongly-correlated quantum systems at finite temperature
Authors: Wang Ding-Zu , Zhang Guo-Feng , Lewenstein Maciej , Ran Shi-Ju
Published: October 2023

Exploring the bulk-boundary correspondences and the boundary-induced phenomena in the strongly-correlated quantum systems belongs to the most fundamental topics of condensed matter physics. In this work, we study the bulk-boundary competition in a simulative Hamiltonian, with which the thermodynamic properties of the infinite-size translationally-invariant system can be optimally mimicked. The simulative Hamiltonian is constructed by introducing local interactions on the boundaries, coined as the entanglement-bath Hamiltonian (EBH) that is analogous to the heat bath. The terms within the EBH are variationally determined by a thermal tensor network method, with coefficients varying with the temperature of the infinite-size system. By treating the temperature as an adjustable hyper-parameter of the EBH, we identify a discontinuity point of the coefficients, dubbed as the ‘boundary quench point’ (BQP), whose physical implication is to distinguish the point, below which the thermal fluctuations from the boundaries to the bulk become insignificant. Fruitful phenomena are revealed when considering the simulative Hamiltonian, with the EBH featuring its own hyper-parameter, under the canonical ensembles at different temperatures. Specifically, a discontinuity in bulk entropy at the BQP is observed. The exotic entropic distribution, the relations between the symmetries of Hamiltonian and BQP, and the impacts from the entanglement-bath dimension are also explored. Our results show that such a singularity differs from those in the conventional thermodynamic phase transition points that normally fall into the Landau–Ginzburg paradigm. Our work provides the opportunities on exploring the exotic phenomena induced by the competition between the bulk and boundaries.
Classification of PTEN missense VUS through exascale simulations
Authors: Sinha Siddharth , Li Jiaheng , Tam Benjamin , Wang San Ming
Published: October 2023

Phosphatase and tensin homolog (PTEN), a tumor suppressor with dual phosphatase properties, is a key factor in PI3K/AKT signaling pathway. Pathogenic germline variation in PTEN can abrogate its ability to dephosphorylate, causing high cancer risk. Lack of functional evidence lets numerous PTEN variants be classified as variants of uncertain significance (VUS). Utilizing Molecular Dynamics (MD) simulations, we performed a thorough evaluation for 147 PTEN missense VUS, sorting them into 66 deleterious and 81 tolerated variants. Utilizing replica exchange molecular dynamic (REMD) simulations, we further assessed the variants situated in the catalytic core of PTEN’s phosphatase domain and uncovered conformational alterations influencing the structural stability of the phosphatase domain. There was a high degree of agreement between our results and the variants classified by Variant Abundance by Massively Parallel Sequencing, saturation mutagenesis, multiplexed functional data and experimental assays. Our extensive analysis of PTEN missense VUS should benefit their clinical applications in PTEN-related cancer.

Significance statement

Classification of PTEN variants affecting its lipid phosphatase activity is important for understanding the roles of PTEN variation in the pathogenesis of hereditary and sporadic malignancies. Of the 3000 variants identified in PTEN, 1296 (43%) were assigned as VUS. Here, we applied MD and REMD simulations to investigate the effects of PTEN missense VUS on the structural integrity of the PTEN phosphatase domain consisting the WPD, P and TI active sites. We classified a total of 147 missense VUS into 66 deleterious and 81 tolerated variants by referring to the control group comprising 54 pathogenic and 12 benign variants. The classification was largely in concordance with these classified by experimental approaches.
Addressing the Ongoing Effects of the Nakba: Experiences and Challenges that Israel’s Arab Social Workers Face
Authors: Allassad Alhuzail Nuzha , Mahajne Ibrahim , Abo Saleh Khawaled Anan
Published: October 2023

The Nakba (‘catastrophe’ in Arabic) began in 1948 with the displacement and dispossession of many Palestinians, leaving a lasting impact on Palestinian society and individual identity. To this day Palestinian social workers must address the difficulties of Palestinians deriving from the Nakba whilst they themselves contend with its ramifications. This descriptive qualitative study, conducted in 2021 using in-depth semi-structured interviews, explored the personal experiences of eighteen Palestinian Arab social workers in Israel who are members of the third generation of the Nakba. Four main themes emerged from the data analysis: ongoing pain, the struggle for justice, the comparison of the Nakba to the Holocaust and perseverance following trauma. However, participants from financially and socially established families in villages whose inhabitants were not displaced reported experiencing growth and resilience. The recommendations include creating safe spaces for Israel’s Arab social workers, where their perspectives can be heard and valued; action by national and international social work organisations to help repeal Israel’s Nakba Law, which seeks to suppress discussion of the Nakba; and inclusion of the Nakba and its consequences in social work curricula. The findings are relevant to social workers in silenced minorities worldwide.
The Future Ain’t What It Used to Be…Out With the Old…In With the Better: Antibacterial Resistance Leadership Group Innovations
Authors: Evans Scott R , Patel Robin , Hamasaki Toshimitsu , Howard-Anderson Jessica , Kinamon Tori , King Heather A , Collyar Deborah , Cross Heather R , Chambers Henry F , Fowler Vance G , Boucher Helen W ,   for the Antibacterial Resistance Leadership Group, Tamma Pranita , Schooley Robert , Banerjee Ritu , Souli Maria , Sund Zoe , Evans Beth , Booth Grant , Estes Leslie , Greenwood-Quaintance Kerryl , Parmar Krupa Mukesh , Cunningham Scott , Schwager Nyssa , Wickward Cathy , Geres Holly , Dai Weixiao , He Yijie , Doernberg Sarah , Satlin Michael , Rouphael Nadine , Tillekeratne Gayani , Baum Keri , Raza Praneeta , Komarow Lauren , Dodd Andrew , Hopkins Deborah , Li Yixuan , Tsalik Ephraim , Holland Thomas , Zhang Shanshan
Published: October 2023

Clinical research networks conduct important studies that would not otherwise be performed by other entities. In the case of the Antibacterial Resistance Leadership Group (ARLG), such studies include diagnostic studies using master protocols, controlled phage intervention trials, and studies that evaluate treatment strategies or dynamic interventions, such as sequences of empiric and definitive therapies. However, the value of a clinical research network lies not only in the results from these important studies but in the creation of new approaches derived from collaborative thinking, carefully examining and defining the most important research questions for clinical practice, recognizing and addressing common but suboptimal approaches, and anticipating that the standard approaches of today may be insufficient for tomorrow. This results in the development and implementation of new methodologies and tools for the design, conduct, analyses, and reporting of research studies. These new methodologies directly impact the studies conducted within the network and have a broad and long-lasting impact on the field, enhancing the scientific value and efficiency of generations of research studies. This article describes innovations from the ARLG in diagnostic studies, observational studies, and clinical trials evaluating interventions for the prevention and treatment of antibiotic-resistant bacterial infections.
Trust but verify? A social epistemology framework of knowledge acquisition and verification practices for fictional entertainment
Authors: Bartsch Anne , Mares Marie-Louise , Schindler Johanna , Kühn Jessica , Krack Ina
Published: October 2023

Fictional entertainment can serve as a vivid and easily comprehensible source of knowledge, but only if audiences are able to tell its kernel of truth apart from fantasy. In this article, we use the lens of social epistemology to develop a theoretical framework of knowledge acquisition and verification practices for fictional entertainment that integrates various extant lines of work on entertainment education, perceived realism, information processing, credibility assessment, and verification strategies. To flesh out the conceptual model derived from top-down theoretical integration, we use an inductive, bottom-up approach to theory building, assisted by qualitative research. The resulting model describes knowledge acquisition from fiction as an essentially social process characterized by a combination of epistemic trust and epistemic vigilance toward fictional content and sources, in which credibility is assessed via social knowledge sharing and verification practices.
At-home Disease Monitoring by Patient-performed Intestinal Ultrasound in Severe Ulcerative Colitis
Authors: Krugliak Cleveland Noa , Miyatani Yusuke , Picker Emma A , Rubin David T
Published: October 2023

Lay Summary

We describe the first reported case of a nonmedically trained patient using a handheld ultrasound device to monitor his ulcerative colitis in real time at home during induction therapy for severe colitis.
Clinical and Endoscopic Outcomes Through 78 Weeks of Tofacitinib Therapy for Ulcerative Colitis in a US Cohort
Authors: Dalal Rahul S , Sharma Puza P , Bains Kanwal , Pruce Jordan C , Allegretti Jessica R
Published: October 2023

Background

Tofacitinib is an oral JAK inhibitor for the treatment of ulcerative colitis (UC). We assessed outcomes through 78 weeks of tofacitinib therapy for UC in a real-world setting.

Methods

This retrospective cohort study included adults initiating tofacitinib for UC from May 1, 2018, to April 1, 2021, at a large academic center in the United States. The primary outcome was steroid-free clinical remission at 78 (+/-4) weeks (SFCR 78; simple clinical colitis activity index ≤2 with no corticosteroid use within 30 days). The secondary outcome was tofacitinib discontinuation due to nonresponse (treatment persistence). Additional outcomes were endoscopic response/remission and adverse events (AEs).

Results

Seventy-three patients initiated tofacitinib, with a median follow-up of 88 weeks. Among patients with available data, 31 of 60 (51.7%) achieved SFCR 78, 21 of 47 (44.7%) achieved endoscopic remission during follow-up, and 25 of 73 (34.2%) discontinued tofacitinib during follow-up due to nonresponse (including 11 patients who required colectomy). Nineteen AEs were reported among 15 patients during follow-up: shingles (n = 4, all without documented vaccinations), deep venous thrombosis (n = 2), elevated liver enzymes (n = 2), skin abscess (n = 2), pneumonia (n = 2), possible miscarriage (n = 2), norovirus (n = 1), COVID-19 (n = 1), lymphopenia (n = 1), Clostridioides difficile infection (n = 1), and heart block (n = 1). One patient discontinued therapy due to an AE (elevated liver enzymes), and no deaths occurred.

Conclusion

Tofacitinib treatment was effective in achieving SFCR for the majority of patients with UC through 78 weeks. Adverse events were consistent with the known safety profile of tofacitinib, and AEs requiring discontinuation were rare. Due to limitations regarding sample size, larger studies are needed to confirm these findings.
Waterpipe tobacco smoking and risk of all-cause mortality: a prospective cohort study
Authors: Le Phuoc Hong , Van Phan Can , Truong Dung Thuy Thi , Ho Nguyet Minh , Shuyna Ikeda , Le Ngoan Tran
Published: October 2023

Background

Despite an increasing proportion of smokers who use non-cigarette products, the harmfulness of these is inconsistent. This study aimed to evaluate the impact of waterpipe tobacco (WTP) smoking on all-cause mortality.

Methods

A prospective cohort study followed up on 35 646 participants from 2007 to 2019 in Northern Viet Nam. Data for each type of cigarette and WTP smoking were collected based on demographic lifestyle and semi-quantitative food frequency questionnaires. Smokers were categorized as current smokers and former smokers who were lifetime ever smokers but stopped smoking >6 months before the interview. Data on all-cause mortality (2449 deaths) were obtained from medical records at the state health facilities. The hazard ratios (HRs) and 95% CIs for mortality were estimated using a Cox proportional-hazards model.

Results

Compared with non-smokers, ever smokers had a higher all-cause mortality risk (HR = 1.29, 95% CI = 1.16–1.43). Current WTP (HR = 1.37, 95% CI = 1.19–1.57), current cigarette (HR = 1.40, 95% CI = 1.22–1.60) and former WTP smokers (HR = 1.39, 95% CI = 1.10–1.76) showed an elevated risk of dying. The mortality risk was significantly elevated in dual smokers using WTP and cigarettes (HR = 1.55, 95% CI = 1.35–1.79) and exclusive WTP smokers (HR = 1.38, 95% CI = 1.21–1.57). Elevated risk was observed for the main targeted attractions of cancer, diabetes and heart diseases. Smoking cessation of >10 years decreased the risk of all-cause mortality (HR = 0.61, 95% CI = 0.44–0.85) and cancer (HR = 0.24, 95% CI = 0.11–0.52).

Conclusions

WTP smoking increases the risk of all-cause mortality. A unique programme to control exposure to WTP should be a high priority in Viet Nam and other countries.
The Evolution of Mobile Phone Surveys in Low- and Middle-Income Countries: A Study of Coverage Structure
Authors: Elkasabi Mahmoud , Khan Azam
Published: October 2023

Mobile phone interviews are becoming an increasingly appealing mode of data collection in low- and middle-income countries. Therefore, we used data from 36 countries to examine mobile phone coverage of adults aged 15–49 years. We paid special attention to the (1) coverage rate (percentage of individuals who own at least one mobile phone) versus penetration rate (mobile phone subscriptions per 100 inhabitants), and (2) proxy-covered population (i.e., persons who do not own mobile phones but are potentially accessible through devices owned by other household members). Study findings suggest that (1) penetration rates notably overestimate mobile phone coverage of the population; (2) mobile phone coverage structure varies substantially; (3) mobile phone owners are more likely to be males, urban residents, literate, married, and relatively wealthy; and (4) proxy-covered adults are distinct with regard to demographic characteristics and survey outcomes in comparison to directly covered and not-covered adults. This study informs practitioners about the current coverage structure in several low- and middle-income countries and promotes proper procedures for studying coverage structure before implementing mobile phone interviews in those countries. Finally, this study introduces the term proxy-coverage and advocates for approaching the proxy-covered population to reduce noncoverage bias, especially in settings where mobile phone sharing among family members is common.
Female pond bats hunt in other areas than males and consume lighter prey when pregnant
Authors: Haarsma Anne-Jifke , Jongejans Eelke , Duijm Elza , van der Graaf Carolien , Lammers Youri , Sharma Milan , Siepel Henk , Gravendeel Barbara
Published: October 2023

Animals with large energy requirements are forced to optimize their hunting strategy, which may result in differentiation of the diet between sexes and across seasons. Here, we examined spatiotemporal variation in the diet of both sexes of the Pond Bat Myotis dasycneme, a species known to have spatial segregation of sexes when the young are born and lactating. Fecal pellets were collected from live animals for a period of 15 years at various locations in the Netherlands. A total of 535 pellets were successfully analyzed by microscopy and an additional 160 pellets by DNA metabarcoding. Morphological and molecular analyses showed that the diet of pregnant and lactating pond bats differed significantly from the diet of females with no reproductive investment. Further analyses of the data showed that pregnant female pond bats are highly dependent on small prey and pupae, mainly nonbiting midges and mosquitoes (Diptera: Chironomidae and Culicidae). These insects can be found in large quantities in peatlands intersected with shallow waterways, the habitat type in which female pond bats were observed more often than males. Our results suggest that during pregnancy the spatial segregation of sexes coincides with sex-specific diets, which might reflect habitat selection based on energy requirements, in addition to lowered intraspecific competition.
OrthoMaM v12: a database of curated single-copy ortholog alignments and trees to study mammalian evolutionary genomics
Authors: Allio Rémi , Delsuc Frédéric , Belkhir Khalid , Douzery Emmanuel J P , Ranwez Vincent , Scornavacca Céline
Published: October 2023

To date, the databases built to gather information on gene orthology do not provide end-users with descriptors of the molecular evolution information and phylogenetic pattern of these orthologues. In this context, we developed OrthoMaM, a database of ORTHOlogous MAmmalian Markers describing the evolutionary dynamics of coding sequences in mammalian genomes. OrthoMaM version 12 includes 15,868 alignments of orthologous coding sequences (CDS) from the 190 complete mammalian genomes currently available. All annotations and 1-to-1 orthology assignments are based on NCBI. Orthologous CDS can be mined for potential informative markers at the different taxonomic levels of the mammalian tree. To this end, several evolutionary descriptors of DNA sequences are provided for querying purposes (e.g. base composition and relative substitution rate). The graphical web interface allows the user to easily browse and sort the results of combined queries. The corresponding multiple sequence alignments and ML trees, inferred using state-of-the art approaches, are available for download both at the nucleotide and amino acid levels. OrthoMaM v12 can be used by researchers interested either in reconstructing the phylogenetic relationships of mammalian taxa or in understanding the evolutionary dynamics of coding sequences in their genomes. OrthoMaM is available for browsing, querying and complete or filtered download at https://orthomam.mbb.cnrs.fr/.
Immunoprecipitation of RNA–DNA hybrid interacting proteins in Trypanosoma brucei reveals conserved and novel activities, including in the control of surface antigen expression needed for immune evasion by antigenic variation
Authors: Girasol Mark J , Briggs Emma M , Marques Catarina A , Batista José M , Beraldi Dario , Burchmore Richard , Lemgruber Leandro , McCulloch Richard
Published: October 2023

RNA–DNA hybrids are epigenetic features of genomes that provide a diverse and growing range of activities. Understanding of these functions has been informed by characterising the proteins that interact with the hybrids, but all such analyses have so far focused on mammals, meaning it is unclear if a similar spectrum of RNA–DNA hybrid interactors is found in other eukaryotes. The African trypanosome is a single-cell eukaryotic parasite of the Discoba grouping and displays substantial divergence in several aspects of core biology from its mammalian host. Here, we show that DNA–RNA hybrid immunoprecipitation coupled with mass spectrometry recovers 602 putative interactors in T. brucei mammal- and insect-infective cells, some providing activities also found in mammals and some lineage-specific. We demonstrate that loss of three factors, two putative helicases and a RAD51 paralogue, alters T. brucei nuclear RNA–DNA hybrid and DNA damage levels. Moreover, loss of each factor affects the operation of the parasite immune survival mechanism of antigenic variation. Thus, our work reveals the broad range of activities contributed by RNA–DNA hybrids to T. brucei biology, including new functions in host immune evasion as well as activities likely fundamental to eukaryotic genome function.
A rice variation map derived from 10 548 rice accessions reveals the importance of rare variants
Authors: Wang Tianyi , He Wenchuang , Li Xiaoxia , Zhang Chao , He Huiying , Yuan Qiaoling , Zhang Bin , Zhang Hong , Leng Yue , Wei Hua , Xu Qiang , Shi Chuanlin , Liu Xiangpei , Guo Mingliang , Wang Xianmeng , Chen Wu , Zhang Zhipeng , Yang Longbo , Lv Yang , Qian Hongge , Zhang Bintao , Yu Xiaoman , Liu Congcong , Cao Xinglan , Cui Yan , Zhang Qianqian , Dai Xiaofan , Guo Longbiao , Wang Yuexing , Zhou Yongfeng , Ruan Jue , Qian Qian , Shang Lianguang
Published: October 2023

Detailed knowledge of the genetic variations in diverse crop populations forms the basis for genetic crop improvement and gene functional studies. In the present study, we analyzed a large rice population with a total of 10 548 accessions to construct a rice super-population variation map (RSPVM), consisting of 54 378 986 single nucleotide polymorphisms, 11 119 947 insertion/deletion mutations and 184 736 presence/absence variations. Assessment of variation detection efficiency for different population sizes revealed a sharp increase of all types of variation as the population size increased and a gradual saturation of that after the population size reached 10 000. Variant frequency analysis indicated that ∼90% of the obtained variants were rare, and would therefore likely be difficult to detect in a relatively small population. Among the rare variants, only 2.7% were predicted to be deleterious. Population structure, genetic diversity and gene functional polymorphism of this large population were evaluated based on different subsets of RSPVM, demonstrating the great potential of RSPVM for use in downstream applications. Our study provides both a rich genetic basis for understanding natural rice variations and a powerful tool for exploiting great potential of rare variants in future rice research, including population genetics and functional genomics.
Engineering of cytosine base editors with DNA damage minimization and editing scope diversification
Authors: Yuan Bo , Zhang Shuqian , Song Liting , Chen Jinlong , Cao Jixin , Qiu Jiayi , Qiu Zilong , Chen Jingqi , Zhao Xing-Ming , Cheng Tian-Lin
Published: October 2023

Cytosine base editors (CBEs), which enable precise C-to-T substitutions, have been restricted by potential safety risks, including DNA off-target edits, RNA off-target edits and additional genotoxicity such as DNA damages induced by double-strand breaks (DSBs). Though DNA and RNA off-target edits have been ameliorated via various strategies, evaluation and minimization of DSB-associated DNA damage risks for most CBEs remain to be resolved. Here we demonstrate that YE1, an engineered CBE variant with minimized DNA and RNA off-target edits, could induce prominent DSB-associated DNA damage risks, manifested as γH2AX accumulation in human cells. We then perform deaminase engineering for two deaminases lamprey LjCDA1 and human APOBEC3A, and generate divergent CBE variants with eliminated DSB-associated DNA damage risks, in addition to minimized DNA/RNA off-target edits. Furthermore, the editing scopes and sequence preferences of APOBEC3A-derived CBEs could be further diversified by internal fusion strategy. Taken together, this study provides updated evaluation platform for DSB-associated DNA damage risks of CBEs and further generates a series of safer toolkits with diversified editing signatures to expand their applications.
RAD51 paralogs synergize with RAD51 to protect reversed forks from cellular nucleases
Authors: Guh Chia-Lun , Lei Kai-Hang , Chen Yi-An , Jiang Yi-Zhen , Chang Hao-Yen , Liaw Hungjiun , Li Hung-Wen , Yen Hsin-Yung , Chi Peter
Published: October 2023

Fork reversal is a conserved mechanism to prevent stalled replication forks from collapsing. Formation and protection of reversed forks are two crucial steps in ensuring fork integrity and stability. Five RAD51 paralogs, namely, RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3, which share sequence and structural similarity to the recombinase RAD51, play poorly defined mechanistic roles in these processes. Here, using purified BCDX2 (RAD51BCD-XRCC2) and CX3 (RAD51C-XRCC3) complexes and in vitro reconstituted biochemical systems, we mechanistically dissect their functions in forming and protecting reversed forks. We show that both RAD51 paralog complexes lack fork reversal activities. Whereas CX3 exhibits modest fork protection activity, BCDX2 significantly synergizes with RAD51 to protect DNA against attack by the nucleases MRE11 and EXO1. DNA protection is contingent upon the ability of RAD51 to form a functional nucleoprotein filament on DNA. Collectively, our results provide evidence for a hitherto unknown function of RAD51 paralogs in synergizing with RAD51 nucleoprotein filament to prevent degradation of stressed replication forks.