bluuebunny/crossref_metadata_2025 huggingface dataset:
(Multi-field) natural inflation and gravitational waves
Authors: Salvio Alberto , Sciusco Simone
Published: March 2024

We provide a detailed study of natural inflation with a periodic non-minimal coupling, which is a well-motivated inflationary model that admits an explicit UV completion. We demonstrate that this construction can satisfy the most recent observational constraints from Planck and the BICEP/Keck collaborations. We also compute the corresponding relic gravitational wave background due to tensor perturbations and show that future space-borne interferometers, such as DECIGO, BBO and ALIA, may be able to detect it. Next, we extend this analysis and establish the validity of these results in a multi-field model featuring an additional R
2 term in the action, which allows us to interpolate between natural and scalaron (a.k.a. Starobinsky) inflation. We investigate the conditions under which the aforementioned future interferometers will have the capability to differentiate between pure natural inflation and natural-scalaron inflation. The latter analysis could open the door to distinguishing between single-field and multi-field inflation through gravitational wave observations in more general contexts.
Time-resolved FRS detection of OH radical for chemical reactions rate measurement
Authors: Plastinina Daria M , Koshlyakov Pavel V , Chesnokov Evgeniy N
Published: March 2024

The time-resolved Faraday rotation spectroscopy method with a DFB diode laser at 1434 nm was used to detect the hydroxyl radical OH in the first overtone region. Experiments were made at the most intense Q(3/2) line of the 2Π3/2 electronic term. The sufficient concentration for radical measurement is 2 × 1012 cm−3, with the resolving time approximately 10−6 s. This resolution is sufficient for studying fast chemical reactions, which was demonstrated by measuring the rate constant of the OH and dimethylsulfide reaction.
Surface growth approach for bulk reconstruction in the AdS/BCFT correspondence*
Authors: Fang 方 Xi-Hao 西浩 , Chen 陈 Fang-Zhong 方中 , Sun 孙 Jia-Rui 佳睿
Published: March 2024

In this study, we extend the surface growth approach for bulk reconstruction into the AdS spacetime with a boundary in the AdS/BCFT correspondence. We show that the geometry in the entanglement wedge with a boundary can be constructed from the direct growth of bulk extremal surfaces layer by layer. Furthermore, we observe that the surface growth configuration in BCFT can be connected with the defect multi scale entanglement renormalization ansatz (MERA) tensor network. Additionally, we investigate the entanglement of purification within the surface growth process, which not only reveals more refined structure of entanglement entropy in the entanglement wedge but also suggests a selection rule for surface growth in the bulk reconstruction.
Development of in situ characterization techniques in molecular beam epitaxy
Authors: Shen Chao , Zhan Wenkang , Li Manyang , Sun Zhenyu , Tang Jian , Wu Zhaofeng , Xu Chi , Xu Bo , Zhao Chao , Wang Zhanguo
Published: March 2024

Ex situ characterization techniques in molecular beam epitaxy (MBE) have inherent limitations, such as being prone to sample contamination and unstable surfaces during sample transfer from the MBE chamber. In recent years, the need for improved accuracy and reliability in measurement has driven the increasing adoption of in situ characterization techniques. These techniques, such as reflection high-energy electron diffraction, scanning tunneling microscopy, and X-ray photoelectron spectroscopy, allow direct observation of film growth processes in real time without exposing the sample to air, hence offering insights into the growth mechanisms of epitaxial films with controlled properties. By combining multiple in situ characterization techniques with MBE, researchers can better understand film growth processes, realizing novel materials with customized properties and extensive applications. This review aims to overview the benefits and achievements of in situ characterization techniques in MBE and their applications for material science research. In addition, through further analysis of these techniques regarding their challenges and potential solutions, particularly highlighting the assistance of machine learning to correlate in situ characterization with other material information, we hope to provide a guideline for future efforts in the development of novel monitoring and control schemes for MBE growth processes with improved material properties.
GHz photon-number resolving detection with high detection efficiency and low noise by ultra-narrowband interference circuits
Authors: Shi Tingting , Fan Yuanbin , Yan Zhengyu , Zhou Lai , Ji Yang , Yuan Zhiliang
Published: March 2024

We demonstrate the photon-number resolution (PNR) capability of a 1.25 GHz gated InGaAs single-photon avalanche photodiode (APD) that is equipped with a simple, low-distortion ultra-narrowband interference circuit for the rejection of its background capacitive response. Through discriminating the avalanche current amplitude, we are able to resolve up to four detected photons in a single detection gate with a detection efficiency as high as 45%. The PNR capability is limited by the avalanche current saturation, and can be increased to five photons at a lower detection efficiency of 34%. The PNR capability, combined with high efficiency and low noise, will find applications in quantum information processing technique based on photonic qubits.
Decoding of unimanual and bimanual reach-and-grasp actions from EMG and IMU signals in persons with cervical spinal cord injury
Authors: Wolf Marvin , Rupp Rüdiger , Schwarz Andreas
Published: March 2024

Objective. Chronic motor impairments of arms and hands as the consequence of a cervical spinal cord injury (SCI) have a tremendous impact on activities of daily life. A considerable number of people however retain minimal voluntary motor control in the paralyzed parts of the upper limbs that are measurable by electromyography (EMG) and inertial measurement units (IMUs). An integration into human-machine interfaces (HMIs) holds promise for reliable grasp intent detection and intuitive assistive device control. Approach. We used a multimodal HMI incorporating EMG and IMU data to decode reach-and-grasp movements of groups of persons with cervical SCI (n = 4) and without (control, n = 13). A post-hoc evaluation of control group data aimed to identify optimal parameters for online, co-adaptive closed-loop HMI sessions with persons with cervical SCI. We compared the performance of real-time, Random Forest-based movement versus rest (2 classes) and grasp type predictors (3 classes) with respect to their co-adaptation and evaluated the underlying feature importance maps. Main results. Our multimodal approach enabled grasp decoding significantly better than EMG or IMU data alone (p

<

0.05). We found the 0.25 s directly prior to the first touch of an object to hold the most discriminative information. Our HMIs correctly predicted 79.3 ± STD 7.4 (102.7 ± STD 2.3 control group) out of 105 trials with grand average movement vs. rest prediction accuracies above 99.64% (100% sensitivity) and grasp prediction accuracies of 75.39 ± STD 13.77% (97.66 ± STD 5.48% control group). Co-adaption led to higher prediction accuracies with time, and we could identify adaptions in feature importances unique to each participant with cervical SCI. Significance. Our findings foster the development of multimodal and adaptive HMIs to allow persons with cervical SCI the intuitive control of assistive devices to improve personal independence.
A simulator for Timepix-like pixel front-ends
Authors: Ballabriga Sune R. , Bromberger H. , Campbell M. , Llopart Cudie X. , Christodoulou P. , Sriskaran V. , Tlustos L.
Published: March 2024

This work presents the development of a front-end simulation code for the Timepix3 readout chip [1], intended as digitizer stage in full detector simulation. The front-end electronics is modelled using an integrator stage and 3 parallel feedback loops with individually configurable time constants. The main feedback discharging the integrator consists of 3 low-pass filtered feedback loops. The leakage current compensation is approximated by an additional independent low-pass filtered feed-back loop. The system noise is modelled using independent bandwidth limited noise channels for pre-amplifier, feedback and threshold noise. The Timepix3 time of arrival (ToA) and time over threshold (ToT) measurement is implemented by a discriminator model with independent rise and fall times and 2 independent clock frequencies for ToA and ToT. The measured dependence of the ToT on the pre-amplifier input charge using test-pulses of a Timepix3 assembly is correctly reproduced for a wide range of discriminator settings.
The development of a laser system for use in the timing performance measurements of CMS HGCAL silicon modules
Authors: Khan F.A. , Noy M. , Steen A. , Monti F. , Ganjour S. ,   the CMS collaboration
Published: March 2024

For optimal operations in the high radiation and pileup environment of the HL-LHC, the CMS-HGCAL requires precise timing information at the level of 30 ps (RMS) for a particle shower. The time measurement in silicon detector modules is performed using a per-channel time-of-arrival discriminator coupled with charge measurement to correct for the time-walk. The module design includes access holes in the PCB and in the sensor passivation to enable infrared laser light to be injected directly into the sensor cells. We present the calibration and timing-in of the system used to perform measurements.
Test and performance of the CMS ECAL barrel data conversion and digital processing ASIC for HL-LHC
Authors: Borca C. ,   the CMS collaboration
Published: March 2024

In preparation for the high luminosity upgrade of the Large Hadron Collider, a new data conversion and digital processing ASIC, called LiTE-DTU, was designed. Implemented in a 65 nm CMOS technology, the LiTE-DTU features two 12-bit 160 MS s-1 successive approximation register time-interleaved ADCs, a data processing unit and enables efficient data transmission at 1.28 Gbps.
The LiTE-DTU has undergone extensive testing in both laboratory and beam tests, demonstrating excellent performance in the pre-production version, showing the production readiness of the design. The results of this comprehensive series of tests will be presented.
Energy distribution of fragments from H2 and H2
+ dissociation by electron impact for the use in numerical models applied to negative ion sources
Authors: Sartori E.
Published: March 2024

In negative hydrogen ion sources, the kinetic energy of the atoms is directly related to the negative ion yield at the caesiated converter, with a larger contribution from hot atoms. The energy distribution of hydrogen atoms is related to the formation process: either the kinetic energy release, resulting from dissociation of the hydrogen molecules or molecular ions, or the proton neutralization either in the volume or during reflection at walls. The interpretation of recent experimental measurements related to the translational energy distribution of atoms or positive ions could profit from accurate inclusion of the initial energy distribution in numerical models. In this work, we focus on the calculation of the kinetic energy release for the various dissociation channels due to electron impact on H2 and H2
+, in the Franck-Condon and delta approximation. Since in negative ion sources non-equilibrium vibrational distributions of H2 are found, the energy distribution of fragments is calculated for all vibrational levels. The inverse cumulative distribution functions related to the main dissociation processes are given, as well as the cumulative distributions for all dissociation channels by electron impact, for simple implementation in Monte Carlo numerical simulations. Finally, the application of the method to few cases of interest for negative ion sources is discussed.
Tumor targeted nanohybrid for dual stimuli responsive and NIR amplified photothermal/photo-induced thermodynamic/chemodynamic combination therapy
Authors: Mehrotra Neha , Pal Kaushik
Published: March 2024

The combination of photodynamic (PDT) and chemodynamic therapy (CDT) for cancer treatment has gathered a lot of attention in recent years. However, its efficacy is severely limited by elevated levels of hypoxia and glutathione (GSH) in the tumor microenvironment (TME). Multifunctional nanoparticles that can help remodel the TME while facilitating PDT/CDT combination therapy are the need of the hour. To this effect, we have developed O2 self-supplying, free radical generating nanohybrids that exhibit near infra-red (NIR) triggered photothermal (PTT)/photo-induced thermodynamic (P-TDT) and CDT for efficient breast cancer treatment. The surface of nanohybrids has been further modified by biointerfacing with cancer cell membrane. The biomimetic nanohybrids have been comprehensively characterized and found to exhibit high 2,2′-azobis-[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) loading, GSH depletion, oxygen self-supply with TME responsive AIPH release. Biological activity assays demonstrate efficient cellular uptake with homotypic targeting, excellent hemo- and cytocompatibility as well as high intracellular reactive oxygen species generation with synergistic cytotoxicity against tumor cells. The multifunctional nanohybrid proposed in the present study provides an attractive strategy for achieving NIR responsive, tumor targeted PTT/P-TDT/CDT combination therapy for breast cancer treatment.
Current development of theragnostic nanoparticles for women’s cancer treatment
Authors: Kashyap Ananya , Kumari Madhubala , Singh Arnika , Mukherjee Koel , Maity Dipak
Published: March 2024

In the biomedical industry, nanoparticles (NPs—exclusively small particles with size ranging from 1–100 nanometres) are recently employed as powerful tools due to their huge potential in sophisticated and enhanced cancer theragnostic (i.e. therapeutics and diagnostics). Cancer is a life-threatening disease caused by carcinogenic agents and mutation in cells, leading to uncontrolled cell growth and harming the body’s normal functioning while affecting several factors like low levels of reactive oxygen species, hyperactive antiapoptotic mRNA expression, reduced proapoptotic mRNA expression, damaged DNA repair, and so on. NPs are extensively used in early cancer diagnosis and are functionalized to target receptors overexpressing cancer cells for effective cancer treatment. This review focuses explicitly on how NPs alone and combined with imaging techniques and advanced treatment techniques have been researched against ‘women’s cancer’ such as breast, ovarian, and cervical cancer which are substantially occurring in women. NPs, in combination with numerous imaging techniques (like PET, SPECT, MRI, etc) have been widely explored for cancer imaging and understanding tumor characteristics. Moreover, NPs in combination with various advanced cancer therapeutics (like magnetic hyperthermia, pH responsiveness, photothermal therapy, etc), have been stated to be more targeted and effective therapeutic strategies with negligible side effects. Furthermore, this review will further help to improve treatment outcomes and patient quality of life based on the theragnostic application-based studies of NPs in women’s cancer treatment.
The establishment of uncertain single pendulum equation and its solutions
*
Authors: Qiu Xiaoyue , Zhu Jiaxuan , Liu Shiqin , Liu Liying
Published: March 2024

The single pendulum equation is commonly used to model the vibration characteristics of a single pendulum subjected to variable forces. A stochastic single pendulum equation driven by Wiener process describes the vibration phenomenon containing a noise term. However, there are also contradictions in some cases. Therefore, in this paper, uncertain single pendulum equation driven by Liu process is proposed to depict noise. Furthermore, analytical solutions as well as the inverse uncertainty distribution (IUD) of solutions for a class of uncertain single pendulum equations are presented. Finally, a paradox related to the stochastic single pendulum equation is given in the appendix.
On-chip fabrication and in-flow 3D-printing of microgel constructs: from chip to scaffold materials in one integral process
Authors: Reineke Benjamin , Paulus Ilona , Löffelsend Sophia , Yu Chien-Hsin , Vinogradov Dmitrii , Meyer Anna , Hazur Jonas , Röder Jonas , Vollmer Madita , Tamgüney Gültekin , Hauschild Stephan , Boccaccini Aldo R , Groll Jürgen , Förster Stephan
Published: March 2024

Bioprinting has evolved into a thriving technology for the fabrication of cell-laden scaffolds. Bioinks are the most critical component for bioprinting. Recently, microgels have been introduced as a very promising bioink, enabling cell protection and the control of the cellular microenvironment. However, the fabrication of the bioinks involves the microfluidic production of the microgels, with a subsequent multistep process to obtain the bioink, which so far has limited its application potential. Here we introduce a direct coupling of microfluidics and 3D-printing for the continuous microfluidic production of microgels with direct in-flow printing into stable scaffolds. The 3D-channel design of the microfluidic chip provides access to different hydrodynamic microdroplet formation regimes to cover a broad range of droplet and microgel diameters. After exiting a microtubing the produced microgels are hydrodynamically jammed into thin microgel filaments for direct 3D-printing into two- and three-dimensional scaffolds. The methodology enables the continuous on-chip encapsulation of cells into monodisperse microdroplets with subsequent in-flow cross-linking to produce cell-laden microgels. The method is demonstrated for different cross-linking methods and cell lines. This advancement will enable a direct coupling of microfluidics and 3D-bioprinting for scaffold fabrication.
Does entanglement enhance single-molecule pulsed biphoton spectroscopy?
Authors: Khan Aiman , Albarelli Francesco , Datta Animesh
Published: March 2024

It depends. For a single molecule interacting with one mode of a biphoton probe, we show that the spectroscopic information has three contributions, only one of which is a genuine two-photon contribution. When all the scattered light can be measured, solely this contribution exists and can be fully extracted using unentangled measurements. Furthermore, this two-photon contribution can, in principle, be matched by an optimised but unentangled single-photon probe. When the matter system spontaneously emits into inaccessible modes, an advantage due to entanglement can not be ruled out. In practice, time-frequency entanglement does enhance spectroscopic performance of the oft-studied weakly-pumped spontaneous parametric down conversion (PDC) probes. For two-level systems and coupled dimers, more entangled PDC probes yield more spectroscopic information, even in the presence of emission into inaccessible modes. Moreover, simple, unentangled measurements can capture between 60% and 90% of the spectroscopic information. We thus establish that biphoton spectroscopy using source-engineered PDC probes and unentangled measurements can provide tangible quantum enhancement. Our work underscores the intricate role of entanglement in single-molecule spectroscopy using quantum light.
Performance-control-orientated hybrid metal additive manufacturing technologies: state of the art, challenges, and future trends
Authors: Lv Jiming , Liang Yuchen , Xu Xiang , Xu Gang , Zhang Hongmei , Lu Haifei , Luo Kaiyu , Cai Jie , Lu Jinzhong
Published: March 2024

Metal additive manufacturing (AM) technologies have made significant progress in the basic theoretical field since their invention in the 1970s. However, performance instability during continuous processing, such as thermal history, residual stress accumulation, and columnar grain epitaxial growth, consistently hinders their broad application in standardized industrial production. To overcome these challenges, performance-control-oriented hybrid AM (HAM) technologies have been introduced. These technologies, by leveraging external auxiliary processes, aim to regulate microstructural evolution and mechanical properties during metal AM. This paper provides a systematic and detailed review of performance-control-oriented HAM technology, which is categorized into two main groups: energy field-assisted AM (EFed AM, e.g. ultrasonic, electromagnetic, and heat) technologies and interlayer plastic deformation-assisted AM (IPDed AM, e.g. laser shock peening, rolling, ultrasonic peening, and friction stir process) technologies. This review covers the influence of external energy fields on the melting, flow, and solidification behavior of materials, and the regulatory effects of interlayer plastic deformation on grain refinement, nucleation, and recrystallization. Furthermore, the role of performance-control-oriented HAM technologies in managing residual stress conversion, metallurgical defect closure, mechanical property improvement, and anisotropy regulation is thoroughly reviewed and discussed. The review concludes with an analysis of future development trends in EFed AM and IPDed AM technologies.
Preparation of single atom catalysts for high sensitive gas sensing
Authors: He Xinxin , Guo Ping , An Xuyang , Li Yuyang , Chen Jiatai , Zhang Xingyu , Wang Lifeng , Dai Mingjin , Tan Chaoliang , Zhang Jia
Published: March 2024

Highlights

The single atom catalysts for high sensitive and selective gas sensor.

A comprehensive overview of preparation strategies for single atom catalysts.

The interactions between the single atom catalysts and target gases as well as their supports.

The typical applications of single atom catalysts in normal gases and volatile organic compounds.
Conclusion
Authors: Collord Michaela
Published: March 2024

This book has presented a fresh analysis of where authoritarian institutions come from and how they order power within a regime. It has traced the trajectories of ruling parties and legislatures from an early period of regime consolidation through subsequent episodes of socio-economic and institutional change. This concluding chapter reviews the main contributions of the book before engaging with three additional areas of inquiry. First, it expands on an earlier discussion of authoritarian discontinuities, examining the significance of John Magufuli’s presidency in Tanzania (2015–2021) and the political rupture it caused. Moving beyond the focus on dominant party regimes, it next engages with the implications of more competitive multiparty politics for legislative strengthening. Finally, it reflects on the relationship between legislative strengthening and democratization, pointing towards a more circumspect assessment of ‘democratic’ consolidation and its transformative potential.
Patient Navigation Plus Tailored Digital Video Disc Increases Colorectal Cancer Screening Among Low-Income and Minority Patients Who Did Not Attend a Scheduled Screening Colonoscopy: A Randomized Trial
Authors: Rawl Susan M , Perkins Susan M , Tong Yan , Katz Mira L , Carter-Bawa Lisa , Imperiale Thomas F , Schwartz Peter H , Fatima Hala , Krier Connie , Tharp Kevin , Shedd-Steele Rivienne , Magnarella Mark , Malloy Caeli , Haunert Laura , Gebregziabher Netsanet , Paskett Electra D , Champion Victoria
Published: March 2024

Background

Up to 50% of people scheduled for screening colonoscopy do not complete this test and no studies have focused on minority and low-income populations. Interventions are needed to improve colorectal cancer (CRC) screening knowledge, reduce barriers, and provide alternative screening options. Patient navigation (PN) and tailored interventions increase CRC screening uptake, however there is limited information comparing their effectiveness or the effect of combining them.

Purpose

Compare the effectiveness of two interventions to increase CRC screening among minority and low-income individuals who did not attend their screening colonoscopy appointment—a mailed tailored digital video disc (DVD) alone versus the mailed DVD plus telephone-based PN compared to usual care.

Methods

Patients (n = 371) aged 45–75 years at average risk for CRC who did not attend a screening colonoscopy appointment were enrolled and were randomized to: (i) a mailed tailored DVD; (ii) the mailed DVD plus phone-based PN; or (iii) usual care. CRC screening outcomes were from electronic medical records at 12 months. Multivariable logistic regression analyses were used to study intervention effects.

Results

Participants randomized to tailored DVD plus PN were four times more likely to complete CRC screening compared to usual care and almost two and a half times more likely than those who were sent the DVD alone.

Conclusions

Combining telephone-based PN with a mailed, tailored DVD increased CRC screening among low-income and minority patients who did not attend their screening colonoscopy appointments and has potential for wide dissemination.
Standing ‘in’ and ‘out’ from the Crowd in a Small Genre: Proximity and Positioning in Applied Linguists’ Email Signatures
Authors: Aslan Erhan , Jaworska Sylvia
Published: March 2024

Neoliberal demands in higher education (HE) amplified by the affordances of digitalisation have led to the emergence of various academic branding practices, one of which is the use of email signatures for identity work and self-promotion. Examining a corpus of 200 email signatures created by applied linguists between 2011 and 2020, this study identifies core and optional moves and how the moves orient to proximity (scholarly communities) and positioning (reputational work). The quantitative analysis of the dataset supported by semi-structured interviews with a group of academics shows that while core moves provide basic identity information, optional moves are used strategically for positioning. A comparison by career stage reveals that mid-career academics utilize more positioning than early-career and established academics. The positioning moves in the second half of the decade draw more on academic achievements, multimodality, and digital presence. The study contributes to an enhanced understanding of how a small and originally inconspicuous genre becomes a space for academic branding and evaluates this development against the increasingly competitive and precarious conditions of the neoliberal HE sector.
Inferring a directed acyclic graph of phenotypes from GWAS summary statistics
Authors: Zilinskas Rachel , Li Chunlin , Shen Xiaotong , Pan Wei , Yang Tianzhong
Published: March 2024

Estimating phenotype networks is a growing field in computational biology. It deepens the understanding of disease etiology and is useful in many applications. In this study, we present a method that constructs a phenotype network by assuming a Gaussian linear structure model embedding a directed acyclic graph (DAG). We utilize genetic variants as instrumental variables and show how our method only requires access to summary statistics from a genome-wide association study (GWAS) and a reference panel of genotype data. Besides estimation, a distinct feature of the method is its summary statistics-based likelihood ratio test on directed edges. We applied our method to estimate a causal network of 29 cardiovascular-related proteins and linked the estimated network to Alzheimer’s disease (AD). A simulation study was conducted to demonstrate the effectiveness of this method. An R package sumdag implementing the proposed method, all relevant code, and a Shiny application are available.
High-dimensional sparse vine copula regression with application to genomic prediction
Authors: Sahin Özge , Czado Claudia
Published: March 2024

High-dimensional data sets are often available in genome-enabled predictions. Such data sets include nonlinear relationships with complex dependence structures. For such situations, vine copula-based (quantile) regression is an important tool. However, the current vine copula-based regression approaches do not scale up to high and ultra-high dimensions. To perform high-dimensional sparse vine copula-based regression, we propose 2 methods. First, we show their superiority regarding computational complexity over the existing methods. Second, we define relevant, irrelevant, and redundant explanatory variables for quantile regression. Then, we show our method’s power in selecting relevant variables and prediction accuracy in high-dimensional sparse data sets via simulation studies. Next, we apply the proposed methods to the high-dimensional real data, aiming at the genomic prediction of maize traits. Some data processing and feature extraction steps for the real data are further discussed. Finally, we show the advantage of our methods over linear models and quantile regression forests in simulation studies and real data applications.
Merging or ensembling: integrative analysis in multiple neuroimaging studies
Authors: Shan Yue , Huang Chao , Li Yun , Zhu Hongtu
Published: March 2024

The aim of this paper is to systematically investigate merging and ensembling methods for spatially varying coefficient mixed effects models (SVCMEM) in order to carry out integrative learning of neuroimaging data obtained from multiple biomedical studies. The ”merged” approach involves training a single learning model using a comprehensive dataset that encompasses information from all the studies. Conversely, the ”ensemble” approach involves creating a weighted average of distinct learning models, each developed from an individual study. We systematically investigate the prediction accuracy of the merged and ensemble learners under the presence of different degrees of interstudy heterogeneity. Additionally, we establish asymptotic guidelines for making strategic decisions about when to employ either of these models in different scenarios, along with deriving optimal weights for the ensemble learner. To validate our theoretical results, we perform extensive simulation studies. The proposed methodology is also applied to 3 large-scale neuroimaging studies.
Estimation of the causal effects of time-varying treatments in nested case-control studies using marginal structural Cox models
Authors: Takeuchi Yoshinori , Hagiwawa Yasuhiro , Komukai Sho , Matsuyama Yutaka
Published: March 2024

When estimating the causal effects of time-varying treatments on survival in nested case-control (NCC) studies, marginal structural Cox models (Cox-MSMs) with inverse probability weights (IPWs) are a natural approach. However, calculating IPWs from the cases and controls is difficult because they are not random samples from the full cohort, and the number of subjects may be insufficient for calculation. To overcome these difficulties, we propose a method for calculating IPWs to fit Cox-MSMs to NCC sampling data. We estimate the IPWs using a pseudo-likelihood estimation method with an inverse probability of sampling weight using NCC samples, and additional samples of subjects who experience treatment changes and subjects whose follow-up is censored are required to calculate the weights. Our method only requires covariate histories for the samples. The confidence intervals are calculated from the robust variance estimator for the NCC sampling data. We also derive the asymptotic properties of the estimator of Cox-MSM under NCC sampling. The proposed methods will allow researchers to apply several case-control matching methods to improve statistical efficiency. A simulation study was conducted to evaluate the finite sample performance of the proposed method. We also applied our method to a motivating pharmacoepidemiological study examining the effect of statins on the incidence of coronary heart disease. The proposed method may be useful for estimating the causal effects of time-varying treatments in NCC studies.
A boosting method to select the random effects in linear mixed models
Authors: Battauz Michela , Vidoni Paolo
Published: March 2024

This paper proposes a novel likelihood-based boosting method for the selection of the random effects in linear mixed models. The nonconvexity of the objective function to minimize, which is the negative profile log-likelihood, requires the adoption of new solutions. In this respect, our optimization approach also employs the directions of negative curvature besides the usual Newton directions. A simulation study and a real-data application show the good performance of the proposal.
Secukinumab in patients with moderate-to-severe hidradenitis suppurativa based on prior biologic exposure: an efficacy and safety analysis from the SUNSHINE and SUNRISE phase III trials
Authors: Zouboulis Christos C , Passeron Thierry , Pariser David , Wozniak Magdalena B , Li Xianjun , Uhlmann Lorenz , Lobach Iryna , Martinez Angela Llobet , Ravichandran Shoba , Alarcon Ivette , Offidani Annamaria , Alam Maryam S , Mendes-Bastos Pedro
Published: March 2024

Lay Summary

Hidradenitis suppurativa (HS) is a chronic skin disease that causes painful boils. HS is common and affects about 0.4% of the world’s population. Treating the condition is difficult, but drugs called ‘biologics’ can help to improve the symptoms. For example, secukinumab is a biologic drug that has been shown to be effective and well-tolerated for the treatment of HS.

In this analysis, we investigated whether previous treatment with biologics could affect the effectiveness and tolerability of secukinumab. This analysis included data from two identical clinical trials (called SUNSHINE and SUNRISE) that recruited adult patients with HS who had moderate-to-severe disease. In these trials, patients took secukinumab 300 mg every 2 weeks or every 4 weeks for 1 year, or a placebo for 4 months and then switched to secukinumab until 1 year. At regular intervals, the effectiveness and tolerability of secukinumab were examined and the results were compared between patients who had previously used another biologic and patients who had never used a biologic before.

After 16 weeks, patients who took secukinumab had better results than the patients who took a placebo, independent of previous biologic use. Secukinumab was still effective and had improved results over 1 year of treatment in both subgroups. Regardless of whether patients had previously been taking another biologic, secukinumab was just as tolerable as placebo and there were no new safety risks.

Our analysis shows that secukinumab is effective and tolerable, regardless of whether patients have previously used another biologic drug.
Association between atopic dermatitis and eating disorders: a cross-sectional study in the All of Us Research Program
Authors: Chen Gloria F , Xu Suzanne , White Marney A , Cohen Jeffrey M
Published: March 2024

We investigated the association between atopic dermatitis (AD) and eating disorders through a cross-sectional study of US adults in the All of Us Research Program, a diverse cohort of over 250 000 participants with a focus on populations traditionally under-represented in biomedical research. Using multivariable analysis, we found that AD was significantly associated with all eating disorders tested, with binge eating disorder having the greatest multivariable odds ratio of 3.58 (95% confidence interval 2.48–5.02, P < 0.001) when adjusted for age, sex, ethnicity and race.
Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration
Authors: Ding Fengfei , Sun Qian , Long Carter , Rasmussen Rune Nguyen , Peng Sisi , Xu Qiwu , Kang Ning , Song Wei , Weikop Pia , Goldman Steven A , Nedergaard Maiken
Published: March 2024

Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes.

Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer’s disease (APP/PS1), amyotrophic lateral sclerosis (ALS) (SOD1G93A) and Huntington’s disease (R6/2) models. Cortical resting [K+]e correlated inversely with neuronal density and the [K+]e buffering rate but correlated positively with the predicted neuronal firing rate. Screening of astrocyte-selective genomic datasets revealed a number of potassium channel genes that were downregulated in these disease models but not in normal ageing. In particular, the inwardly rectifying potassium channel Kcnj10 was downregulated in ALS and Huntington’s disease models but not in normal ageing, while Fxyd1 and Slc1a3, each of which acts as a negative regulator of potassium uptake, were each upregulated by astrocytes in both Alzheimer’s disease and ALS models. Chronic elevation of [K+]e in response to changes in gene expression and the attendant neuronal hyperexcitability may drive the neuronal loss characteristic of these neurodegenerative diseases. These observations suggest that the dysregulation of extracellular K+ homeostasis in a number of neurodegenerative diseases could be due to aberrant astrocytic K+ buffering and as such, highlight a fundamental role for glial dysfunction in neurodegeneration.
TMEM16A inhibits autophagy and promotes the invasion of hypopharyngeal squamous cell carcinoma through mTOR pathway
Authors: Yang Xin , Cui Limei , Liu Zhonglu , Li Yumei , Wu Xinxin , Tian Ruxian , Jia Chuanliang , Ren Chao , Mou Yakui , Song Xicheng
Published: March 2024

Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared with normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.
Pulse azathioprine and low-dose methotrexate vs. standard-dose methotrexate in treatment of patients with moderate-to-severe psoriasis: a randomized controlled trial
Authors: El-Komy Mohamed Hussein Medhat , Sayed Khadiga S , Gawish Gehad , Elaguizy Menatallah Mohamed , Azzazi Yousra
Published: March 2024

Background

Psoriasis is a common chronic, immune-mediated inflammatory skin disease. Despite the availability of several systemic therapeutic agents, treatment of psoriasis remains a challenge because of the associated adverse effects and/or the financial burden of these medications, given the chronicity of the disease.

Objectives

We aimed to compare the efficacy and safety of combined pulse azathioprine (AZA) and low-dose methotrexate (MTX) vs. a conventional dose of MTX in patients with chronic plaque psoriasis.

Methods

In this randomized controlled trial, 67 patients with moderate-to-severe plaque psoriasis were randomized into two groups, receiving either combined pulse AZA (300 mg weekly dose) and low-dose MTX (10 mg weekly) or conventional-dose MTX (0.3 mg kg−1 per week) for 16 weeks. Patients were assessed for treatment response using the Psoriasis Area and Severity Index (PASI) score and for the development of any adverse effects at weeks 12 and 16, and for a further 3 months after stopping treatment.

Results

A statistically significantly higher proportion of the patients receiving combined pulse AZA and low-dose MTX achieved ≥ 90% improvement in PASI and 100% improvement (PASI 100) at week 12, and PASI 100 at week 16, compared with those receiving the conventional dose of MTX as monotherapy. No serious adverse events were reported during the entire study period in the two groups.

Conclusions

Combination therapy using pulse AZA and low-dose MTX can be an efficacious treatment for moderate-to-severe plaque psoriasis, with a relatively good safety profile.
An exophytic red–purple nodule on the hip
Authors: Sun Lanyu , Duarte Sofia , Brazão Cláudia , Mancha Dora , de Vasconcelos Pedro , Soares-de-Almeida Luís , Filipe Paulo
Published: March 2024

A 35-year-old man with Fitzpatrick skin type IV, born in Brazil, presented to the dermatology clinic with a 3-month history of an asymptomatic growth on the left hip. He reported no prior history of trauma.
Utilizing graph convolutional networks for identification of mild cognitive impairment from single modal fMRI data: a multiconnection pattern combination approach
Authors: He Jie , Wang Peng , He Jun , Sun Chenhao , Xu Xiaowen , Zhang Lei , Wang Xin , Gao Xin
Published: March 2024

Mild cognitive impairment plays a crucial role in predicting the early progression of Alzheimer’s disease, and it can be used as an important indicator of the disease progression. Currently, numerous studies have focused on utilizing the functional brain network as a novel biomarker for mild cognitive impairment diagnosis. In this context, we employed a graph convolutional neural network to automatically extract functional brain network features, eliminating the need for manual feature extraction, to improve the mild cognitive impairment diagnosis performance. However, previous graph convolutional neural network approaches have primarily concentrated on single modes of brain connectivity, leading to a failure to leverage the potential complementary information offered by diverse connectivity patterns and limiting their efficacy. To address this limitation, we introduce a novel method called the graph convolutional neural network with multimodel connectivity, which integrates multimode connectivity for the identification of mild cognitive impairment using fMRI data and evaluates the graph convolutional neural network with multimodel connectivity approach through a mild cognitive impairment diagnostic task on the Alzheimer’s Disease Neuroimaging Initiative dataset. Overall, our experimental results show the superiority of the proposed graph convolutional neural network with multimodel connectivity approach, achieving an accuracy rate of 92.2% and an area under the Receiver Operating Characteristic (ROC) curve of 0.988.
Auditory prediction errors in sound frequency and duration generated different cortical activation patterns in the human brain: an ECoG study
Authors: Takasago Megumi , Kunii Naoto , Fujitani Shigeta , Ishishita Yohei , Tada Mariko , Kirihara Kenji , Komatsu Misako , Uka Takanori , Shimada Seijiro , Nagata Keisuke , Kasai Kiyoto , Saito Nobuhito
Published: March 2024

Sound frequency and duration are essential auditory components. The brain perceives deviations from the preceding sound context as prediction errors, allowing efficient reactions to the environment. Additionally, prediction error response to duration change is reduced in the initial stages of psychotic disorders. To compare the spatiotemporal profiles of responses to prediction errors, we conducted a human electrocorticography study with special attention to high gamma power in 13 participants who completed both frequency and duration oddball tasks. Remarkable activation in the bilateral superior temporal gyri in both the frequency and duration oddball tasks were observed, suggesting their association with prediction errors. However, the response to deviant stimuli in duration oddball task exhibited a second peak, which resulted in a bimodal response. Furthermore, deviant stimuli in frequency oddball task elicited a significant response in the inferior frontal gyrus that was not observed in duration oddball task. These spatiotemporal differences within the Parasylvian cortical network could account for our efficient reactions to changes in sound properties. The findings of this study may contribute to unveiling auditory processing and elucidating the pathophysiology of psychiatric disorders.
Transcatheter aortic valve implantation for structural valve deterioration of homograft surgical aortic valve using SAPIEN3 Ultra RESILIA: a case report
Authors: Mizutani Kazuki , Ueno Masafumi , Sakaguchi Genichi , Nakazawa Gaku
Published: March 2024

Background

There are a few case reports regarding transcatheter aortic valve implantation (TAVI) for deteriorated surgical homograft.

Case summary

We present a case of severe structural valve deterioration (SVD) of homograft surgical aortic valve presenting severe aortic regurgitation in an 84-year-old man with decompensated heart failure. We performed TAVI in homograft valve using 23 mm SAPIEN3 Ultra RESILIA. The resulting grade of paravalvular regurgitation was trace, the post-operative effective orifice area (EOA) was 1.66 cm2 (index EOA: 1.19 cm2/m2), and device success was achieved.

Discussion

Stented bioprosthetic valves are more commonly implanted than mechanical and stentless bioprosthetic valves. In the 1980s and the early 1990s, homografts became particularly popular as alternatives to stented valves. There are several reports of TAVI for homograft SVD, but the paravalvular leakage grade is worse than that of redo-surgical aortic valve replacement, although the mortality rate is lower. However, the valves used in these reports were from older valves such as SAPIEN XT or SAPIEN3. There are no reports using SAPIEN3 Ultra RESILIA with a significant reduction in paravalvular leak due to an external textured polyethylene terephthalate skirt extending 40% higher above the valve inflow than the classical SAPIEN3, which is now available. Transcatheter aortic valve implantation using SAPIEN3 Ultra RESILIA showed good therapeutic efficacy.