bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast and efficient detection of a single photon with hole-patterned superconductor microstrips
Authors: Li Feiyan , Guo Yuqing , Liu Kangjie , Zhang Labao , Chen Qi , Wang Xiaohan , Zhang Biao , Dai Yue , Tan Jingrou , He Guanglong , Fei Yue , Wang Hao , Tu Xuecou , Zhao Qingyuan , Jia Xiaoqing , Kang Lin , Chen Jian , Wu Peiheng
Published: September 2022

In this Letter, we report on pattern engineering in superconducting microstrips to achieve a fast and efficient detection of a single-photon over a large detection area. The proposed detector is composed of hole-patterned superconductor microstrips fabricated with a 5-nm-thick amorphous molybdenum silicide film. It exhibits a saturated internal detection efficiency at 1550 nm with a negligible dark count rate and a recovery time of 9 ns with a large detection area (50 × 50 μm2). The simulation reveals that the holes patterned in the superconductor microstrip stimulate the nucleation of the vortex, which constitutes a major key to achieving the efficient detection of photons. This work paves the way for the facile and prolonged regulation of vortex nucleation in superconductors, which shows promise for developing high-performance large-area superconductor single-photon detectors.
A high-resolution MEMS magnetoresistive sensor utilizing magnetic tunnel junction motion modulation driven by the piezoelectric resonator
Authors: Lyu Haoqi , Liu Zhenxi , Wang Zheng , Yang Wuhao , Xiong Xingyin , Chen Jiamin , Zou Xudong
Published: September 2022

High-sensitivity MEMS magnetoresistive (MR) sensors have attracted ever-increasing attention due to their ability to detect weak magnetic fields, but the resolution is severely limited by the 1/f noise. This paper reports a MEMS MR sensor that can effectively suppress the 1/f noise by modulating the magnetic field signal to the higher frequency region utilizing magnetic tunnel junction vertical motion modulation based on the MEMS piezoelectric cantilever resonator. The magnetic sensitivity can be increased to 2283.3%/mT with a high magnetic gain of 39.3 by integrating the structure-optimized fixed magnetic flux concentrators. The signal-to-noise ratio of the MEMS MR sensor can be improved by three orders of magnitude and the 160 pT/√Hz resolution can be reached. These results make the MEMS MR sensor based on the MTJ motion modulation a competitive candidate in the pico-Tesla magnetic detection.
On rationality of C-graded vertex algebras and applications to Weyl vertex algebras under conformal flow
Authors: Barron Katrina , Batistelli Karina , Orosz Hunziker Florencia , Pedić Tomić Veronika , Yamskulna Gaywalee
Published: September 2022

Using the Zhu algebra for a certain category of C-graded vertex algebras V, we prove that if V is finitely Ω-generated and satisfies suitable grading conditions, then V is rational, i.e., it has semi-simple representation theory, with a one-dimensional level zero Zhu algebra. Here, Ω denotes the vectors in V that are annihilated by lowering the real part of the grading. We apply our result to the family of rank one Weyl vertex algebras with conformal element ωμ parameterized by μ∈C and prove that for certain non-integer values of μ, these vertex algebras, which are non-integer graded, are rational, with a one-dimensional level zero Zhu algebra. In addition, we generalize this result to appropriate C-graded Weyl vertex algebras of arbitrary ranks.
Lightweight design of the transonic centrifugal impeller based on fluid–structure coupling
Authors: Li Huanjun , Zhang Yimin
Published: September 2022

The impeller is the core component of the centrifugal compressor. Aiming to solve problems related to a large mass, high-energy consumption, and large vibration of the existing centrifugal impeller, a semi-open supersonic centrifugal impeller provided by Krain et al. was redesigned in this paper. The redesign was based on Tsai–Wu failure theory and the two-way fluid–structure coupling method. First, the geometric and numerical models were established using the geometric data found in the literature. Then, the established geometric and numerical models were verified through experimental data. Finally, the impeller was optimized from three aspects: material lightweight, composite material layering, and tip clearance. The results have shown that following the optimization, the maximum impeller stress was reduced by 48.77% when compared to the traditional 17-4PH material impeller. The maximum vibration deformation was reduced by 60.4%, as well as the resonance probability. The pressure ratio was increased by 0.8%, and the pressure and velocity reverse gradient trend near the blade tip were significantly reduced, while the flow field was more stable. The research results presented in this paper hence provide a basis for the application of composite materials in centrifugal impellers.
Control of three-dimensional separation due to sharp fins using co-rotating vanes ahead of quasi-conical and conical zones
Authors: Verma Shashi Bhushan , Chidambaranathan Manisankar
Published: September 2022

This experimental investigation studies the effect of an array of 30° inclined co-rotating vanes in controlling a three-dimensional interaction generated by a 15° semi-infinite sharp fin at Mach 2.05. The array is located upstream of the quasi-conical and conical zones of interaction. The primary objective is to study variation in (i) vane chord length c/h = 7.2, 4.2, and 2.5 and (ii) vane height h/δ = 0.3, 0.5, and 0.75 for c/h = 2.5 case in controlling the interaction. Control with the smallest chord length of c/h = 2.5 and h/δ = 0.75 shows the most promising result relative to vanes with longer chord lengths. The vortex trails from this configuration penetrate deeply into the quasi-conical zone of interaction, thereby modifying it both azimuthally and radially. The plateau pressure in the conical region of interaction shows a reduction of approximately 60% with an accompanied reduction in the separation shock strength by nearly 70% for this case. Implementing control in either quasi-conical or conical zones reduces the overall control effectiveness considerably. Removing vanes ahead of quasi-conical zone reduces the effectiveness of favorably modifying the flow development in this region. The bow shock formed ahead of the first vane interacts with the three-dimensional interaction creating a pressure jump that separates the region of vortex influence from that of no control.
On the prediction of noise generated by urban air mobility (UAM) vehicles. I. Integration of fundamental acoustic metrics
Authors: Little Daniel S. , Majdalani Joseph , Hartfield Roy J. , Ahuja Vivek
Published: September 2022

This work identifies and explores several aeroacoustic metrics that allow for urban air mobility (UAM) vehicle noise prediction. An increase in production and use of UAM and distributed electric propulsion vehicles within populated civilian areas stands behind the need to minimize the noise produced by these vehicles. The Federal Aviation Administration's (FAA's) strict noise regulations on UAM aircraft compels designers to place a significant emphasis, early in the design phase, on the characterization and analysis of the external noise generated by these vehicles, namely, to ensure their design viability. To accomplish this, the present study focuses on the analysis and interpretation of predicted noise signals using a set of characteristic metrics that can be instrumental at guiding the design process. Following a thorough review of metrics standardized by the International Civil Aviation Organization as well as the FAA, seven general metrics are identified, evaluated, and discussed in the context of UAM noise prediction. When used in conjunction with a modern surface-vorticity panel code, these metrics are shown to provide an effective assortment of tools to concisely describe UAM-based acoustic signal properties.
Dynamics of racial disparities in all-cause mortality during the COVID-19 pandemic
Authors: Aschmann Hélène E. , Riley Alicia R. , Chen Ruijia , Chen Yea-Hung , Bibbins-Domingo Kirsten , Stokes Andrew C. , Glymour M. Maria , Kiang Mathew V.
Published: September 2022

As research documenting disparate impacts of COVID-19 by race and ethnicity grows, little attention has been given to dynamics in mortality disparities during the pandemic and whether changes in disparities persist. We estimate age-standardized monthly all-cause mortality in the United States from January 2018 through February 2022 for seven racial/ethnic populations. Using joinpoint regression, we quantify trends in race-specific rate ratios relative to non-Hispanic White mortality to examine the magnitude of pandemic-related shifts in mortality disparities. Prepandemic disparities were stable from January 2018 through February 2020. With the start of the pandemic, relative mortality disadvantages increased for American Indian or Alaska Native (AIAN), Native Hawaiian or other Pacific Islander (NHOPI), and Black individuals, and relative mortality advantages decreased for Asian and Hispanic groups. Rate ratios generally increased during COVID-19 surges, with different patterns in the summer 2021 and winter 2021/2022 surges, when disparities approached prepandemic levels for Asian and Black individuals. However, two populations below age 65 fared worse than White individuals during these surges. For AIAN people, the observed rate ratio reached 2.25 (95% CI = 2.14, 2.37) in October 2021 vs. a prepandemic mean of 1.74 (95% CI = 1.62, 1.86), and for NHOPI people, the observed rate ratio reached 2.12 (95% CI = 1.92, 2.33) in August 2021 vs. a prepandemic mean of 1.31 (95% CI = 1.13, 1.49). Our results highlight the dynamic nature of racial/ethnic disparities in mortality and raise alarm about the exacerbation of mortality inequities for Indigenous groups due to the pandemic.
Coherent emission from surface Josephson plasmons in striped cuprates
Authors: Nicoletti D. , Buzzi M. , Fechner M. , Dolgirev P. E. , Michael M. H. , Curtis J. B. , Demler E. , Gu G. D. , Cavalleri A.
Published: September 2022

The interplay between charge order and superconductivity remains one of the central themes of research in quantum materials. In the case of cuprates, the coupling between striped charge fluctuations and local electromagnetic fields is especially important, as it affects transport properties, coherence, and dimensionality of superconducting correlations. Here, we study the emission of coherent terahertz radiation in single-layer cuprates of the La
2-x
Ba
x
CuO
4
family, for which this effect is expected to be forbidden by symmetry. We find that emission vanishes for compounds in which the stripes are quasi-static but is activated when
c
-axis inversion symmetry is broken by incommensurate or fluctuating charge stripes, such as in La
1.905
Ba
0.095
CuO
4
and in La
1.845
Ba
0.155
CuO
4
. In this case, terahertz radiation is emitted by surface Josephson plasmons, which are generally dark modes, but couple to free space electromagnetic radiation because of the stripe modulation.
Recycling of cell surface membrane proteins from yeast endosomes is regulated by ubiquitinated Ist1
Authors: Laidlaw Kamilla M.E. , Calder Grant , MacDonald Chris
Published: September 2022

Upon internalization, many surface membrane proteins are recycled back to the plasma membrane. Although these endosomal trafficking pathways control surface protein activity, the precise regulatory features and division of labor between interconnected pathways are poorly defined. In yeast, we show recycling back to the surface occurs through distinct pathways. In addition to retrograde recycling pathways via the late Golgi, used by synaptobrevins and driven by cargo ubiquitination, we find nutrient transporter recycling bypasses the Golgi in a pathway driven by cargo deubiquitination. Nutrient transporters rapidly internalize to, and recycle from, endosomes marked by the ESCRT-III associated factor Ist1. This compartment serves as both “early” and “recycling” endosome. We show Ist1 is ubiquitinated and that this is required for proper endosomal recruitment and cargo recycling to the surface. Additionally, the essential ATPase Cdc48 and its adaptor Npl4 are required for recycling, potentially through regulation of ubiquitinated Ist1. This collectively suggests mechanistic features of recycling from endosomes to the plasma membrane are conserved.
ADJUST: a dictionary-based joint reconstruction and unmixing method for spectral tomography
Authors: Zeegers Mathé T , Kadu Ajinkya , van Leeuwen Tristan , Batenburg Kees Joost
Published: September 2022

Advances in multi-spectral detectors are causing a paradigm shift in x-ray computed tomography (CT). Spectral information acquired from these detectors can be used to extract volumetric material composition maps of the object of interest. If the materials and their spectral responses are known a priori, the image reconstruction step is rather straightforward. If they are not known, however, the maps as well as the responses need to be estimated jointly. A conventional workflow in spectral CT involves performing volume reconstruction followed by material decomposition, or vice versa. However, these methods inherently suffer from the ill-posedness of the joint reconstruction problem. To resolve this issue, we propose ‘A Dictionary-based Joint reconstruction and Unmixing method for Spectral Tomography’ (ADJUST). Our formulation relies on forming a dictionary of spectral signatures of materials common in CT and prior knowledge of the number of materials present in an object. In particular, we decompose the spectral volume linearly in terms of spatial material maps, a spectral dictionary, and the indicator of materials for the dictionary elements. We propose a memory-efficient accelerated alternating proximal gradient method to find an approximate solution to the resulting bi-convex problem. From numerical demonstrations on several synthetic phantoms, we observe that ADJUST performs exceedingly well compared to other state-of-the-art methods. Additionally, we address the robustness of ADJUST against limited and noisy measurement patterns. The demonstration of the proposed approach on a spectral micro-CT dataset shows its potential for real-world applications. Code is available at https://github.com/mzeegers/ADJUST.
Accurate measures of changes in regional lung air volumes from chest x-rays of small animals
Authors: O’Connell D W , Morgan K S , Ruben G , Croton L C P , Pollock J A , Croughan M K , McGillick E V , Wallace M J , Crossley K J , Pryor E J , Lewis R A , Hooper S B , Kitchen M J
Published: September 2022

Objective. To develop a robust technique for calculating regional volume changes within the lung from x-ray radiograph sequences captured during ventilation, without the use of computed tomography (CT). Approach. This technique is based on the change in transmitted x-ray intensity that occurs for each lung region as air displaces the attenuating lung tissue. Main results. Lung air volumes calculated from x-ray intensity changes showed a strong correlation (R
2 = 0.98) against the true volumes, measured from high-resolution CT. This correlation enables us to accurately convert projected intensity data into relative changes in lung air volume. We have applied this technique to measure changes in regional lung volumes from x-ray image sequences of mechanically ventilated, recently-deceased newborn rabbits, without the use of CT. Significance. This method is suitable for biomedical research studies,enabling quantitative regional measurement of relative lung air volumes at high temporal resolution, and shows great potential for future clinical application.
Characterization of large LGAD sensors for proton counting in particle therapy
Authors: Villarreal O.A.M. , Peroglio G. , Vignati A. , Giordanengo S. , Milian F.M. , Ferrero M. , Menzio L. , Abujami M. , Galeone C. , Ali O.H. , Vignali M.C. , Borghi G. , Ficorella F. , Cirio R. , Monaco V. , Sacchi R.
Published: September 2022

A proton counter prototype based on Low Gain Avalanche Detector (LGAD) technology is being developed for the online monitoring of the fluence rate of therapeutic proton beams. The laboratory characterization of thin (45 μm and 60 μm) LGAD sensors segmented in 146 strips with an unprecedented large area of 2.6 × 2.6 cm2, covering the entire beam cross-section, is presented and discussed. The production includes 14 wafers with different characteristics, designed and produced at Fondazione Bruno Kessler (FBK) of Trento in 2020. The laboratory characterization was carried out at FBK, right after production, and at the University of Torino, after cutting the sensors, using a probe station with a power analyzer for the static DC electrical tests. The tests proved that the production was of very high quality. From 16 sensors randomly selected from different wafers, we observed consistency between the measurements performed at FBK and at the University of Torino, indicating that the cut did not degrade the performance. The sensors were also exposed to the clinical proton beam of the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy). The results show that LGADs allow achieving, in a very thin active thickness, a good separation between the proton signal, a peak of a very short duration, and the noise. This, combined with the large active area, will allow counting protons delivered with high efficiency at the high rates of a clinical beam.
Monte Carlo simulation of SiPMs with GATE
Authors: Mehadji Brahim , Dupont Mathieu , Fougeron Denis , Morel Christian
Published: September 2022

Silicon photomultipliers (SiPMs) replace photomultiplier tubes (PMTs) for the detection of light in many applications, particularly in high energy physics and medical imaging. We describe a flexible implementation of a SiPM model for the GATE Monte Carlo simulation platform, which is based on the SiPM noise description proposed by Rosado and Hidalgo, and describe an easy and effective method to determine and instantiate the SiPM noise model with simple measurements. We also simulate the micro-cell Single Photon Time Resolution (SPTR) and describe its measurement.
Novel prototype tower structure for the dual-readout fiber calorimeter
Authors: Karadzhinova-Ferrer A. , Agarwala J. , Ampilogov N. , Chmill V. , Ferrari R. , Freddi A. , Gaudio G. , Gigli S.G. , Samec Ž. , Santoro R. , Scagliotti C. , Vercellati F.
Published: September 2022

In this paper, we report on a novel cost-effective module structure for future Dual-Readout fiber Calorimetry. We have designed and constructed the system required for the fabrication of the first proof-of-concept prototype module. The instruments, the procedures and the quality control tools used in the assembly of the prototype, and its equipment, are described exhaustively. A mechanical precision of 50 μm required for the interlocking of the tower structures into a compact module has been achieved. A similar system will be used for the assembly of a full-scale prototype based on the Dual-Readout technique.
Oral mucositis on a chip: modeling induction by chemo- and radiation treatments and recovery
Authors: Ly Khanh L , Luo Xiaolong , Raub Christopher B
Published: September 2022

Oral mucositis (OM) is a debilitating complication affecting roughly 70% of head and neck cancer patients receiving chemotherapy and/or radiation treatment. No broadly effective preventative treatment for OM exists. Therefore, an in vitro model of cancer treatment-induced OM would aid studies into possible origins of the pathology and future drug targets to ameliorate it. In this study, we present a microfluidic oral mucosa triculture tissue construct consisting of a keratinocyte layer attached to a subepithelial fibroblast and endothelial cell-embedded collagen gel. To address the typically low stability of mucosal constructs in microfluidics, ruthenium-catalyzed photocrosslinking was implemented to strengthen the collagen gel and prevent the invasion of keratinocytes, thus maintaining tissue construct geometry and oral mucosa barrier function for over 18 d of culture. Next, the OM chip was exposed to cisplatin (day 10) and damaging radiation (day 11, ± cisplatin at day 10), mimicking damage from cancer therapy. Damage to and then recovery of the tissue layers and function were observed over days 11–18. Therefore, several important features of OM induction and resolution were modeled in microfluidic culture. The OM model on a chip allows for more sophisticated studies into mechanisms of OM and potential treatments.
Development of a high-throughput micropatterned agarose scaffold for consistent and reproducible hPSC-derived liver organoids
Authors: Jiang Shanqing , Xu Fang , Jin Menglong , Wang Zhen , Xu Xiaodong , Zhou Ying , Wang Jibo , Gu Longjun , Fan Han , Fan Yuhang , Zhou Zhangxian , Li Changyong , Chen Pu
Published: September 2022

Liver organoids represent emerging human-relevant in vitro liver models that have a wide range of biomedical applications in basic medical studies and preclinical drug discovery. However, the generation of liver organoids currently relies on the conventional Matrigel dome method, which lacks precise microenvironmental control over organoid growth and results in significant heterogeneity of the formed liver organoids. Here, we demonstrate a novel high-throughput culture method to generate uniform liver organoids from human pluripotent stem cell-derived foregut stem cells in micropatterned agarose scaffold. By using this approach, more than 8000 uniformly-sized liver organoids containing liver parenchyma cells, non-parenchymal cells, and a unique stem cell niche could be efficiently and reproducibly generated in a 48-well plate with a size coefficient of variation significance smaller than that in the Matrigel dome. Additionally, the liver organoids highly expressed liver-specific markers, including albumin (ALB), hepatocyte nuclear factor 4 alpha (HNF4α), and alpha-fetoprotein (AFP), and displayed liver functions, such as lipid accumulation, glycogen synthesis, ALB secretion, and urea synthesis. As a proof of concept, we evaluated the acute hepatotoxicity of acetaminophen (APAP) in these organoids and observed APAP-induced liver fibrosis. Overall, we expect that the liver organoids will facilitate wide biomedical applications in hepatotoxicity analysis and liver disease modeling.
A Simulation Study Comparing the Performance of Time-Varying Inverse Probability Weighting and G-Computation in Survival Analysis
Authors: Rudolph Jacqueline E , Schisterman Enrique F , Naimi Ashley I
Published: September 2022

Inverse probability weighting (IPW) and g-computation are commonly used in time-varying analyses. To inform decisions on which to use, we compared these methods using a plasmode simulation based on data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial (June 15, 2007–July 15, 2011). In our main analysis, we simulated a cohort study of 1,226 individuals followed for up to 10 weeks. The exposure was weekly exercise, and the outcome was time to pregnancy. We controlled for 6 confounding factors: 4 baseline confounders (race, ever smoking, age, and body mass index) and 2 time-varying confounders (compliance with assigned treatment and nausea). We sought to estimate the average causal risk difference by 10 weeks, using IPW and g-computation implemented using a Monte Carlo estimator and iterated conditional expectations (ICE). Across 500 simulations, we compared the bias, empirical standard error (ESE), average standard error, standard error ratio, and 95% confidence interval coverage of each approach. IPW (bias = 0.02; ESE = 0.04; coverage = 92.6%) and Monte Carlo g-computation (bias = −0.01; ESE = 0.03; coverage = 94.2%) performed similarly. ICE g-computation was the least biased but least precise estimator (bias = 0.01; ESE = 0.06; coverage = 93.4%). When choosing an estimator, one should consider factors like the research question, the prevalences of the exposure and outcome, and the number of time points being analyzed.
Compassion Fatigue, Compassion Satisfaction, Burnout and Alcohol Use Among Dental Hygienists
Authors: Brooks Jaime , Giblin-Scanlon Lori , Boyd Linda D , Vineyard Jared
Published: September 2022

Aims

The purpose of this study was to investigate the relationship between demographics, compassion fatigue (CF), compassion satisfaction (CS), burnout (BO) and alcohol use among dental hygienists (DHs).

Methods

The web-based survey consisting of two validated instruments [Alcohol Use Disorders Identification Test (AUDIT) and Professional Quality of Life] to measure alcohol use, CF, CS and BO was conducted with a convenience sample of DHs (n = 963).

Results

The completion rate was 81.6% (n = 786). Nearly one in five DHs (19.1%) reported having their alcohol consumption influenced by the Coronavirus disease 2019 pandemic at least moderately. The number of hours worked per week (x) and AUDIT scores (y) were fully mediated by BO (m) (P < 0.001); the average number of hours worked per week (x) and AUDIT scores (y) were fully mediated by CF (m) (P < 0.001); the average number of patients seen per day (x) was a predictor of AUDIT scores (y) when partially mediated by BO (m) (P < 0.001); and age (x) was a predictor of AUDIT scores (y), mediated by CS (m). Results showed that one in four DHs could qualify for binge drinking (25.6%, n = 177) and 15.1% experienced blackout drinking episodes within the past year (n = 118).

Conclusion

Mediating relationships exist between demographics, CF, CS, BO and alcohol use among DHs. More research needs to be conducted on alcohol use and CF among DHs and protective factors that may reduce the risk of BO, CF or alcohol use.
Defining Internal Tissue Closure: High-Resolution Ultrasound Evaluation of Interi—A Novel Internal Tissue Closure System
Authors: Alfonso David , Bengtson Bradley , McGuire Patricia
Published: September 2022

Background

Seroma remains a leading postsurgical complication in plastic surgery. Conventional drains are ineffective in clearing blood and fluid and closing down surgical spaces. The Interi (Internal Closure System, IC Surgical, Grand Rapids, MI) is comprised of a novel branching internal manifold attached to a self-contained portable pump with a higher, consistent, continuous negative pressure, may reduce this long-standing issue. In addition, high-resolution ultrasound (HRUS) has emerged as an ideal tool to visualize structures, fluid collections, and seromas internally.

Objectives

This study evaluates Interi in full abdominoplasty patients utilizing HRUS to evaluate Interi's ability to evacuate blood and fluid, hold internal tissues together and document, for the first time, what internal tissue healing actually looks like radiographically.

Methods

An IRB approved, Contract Research Organization reviewed retrospective study evaluated consecutive patients undergoing full abdominoplasty utilizing Interi from July 2020 through March 2021 by three plastic surgeons. HRUS visualized and confirmed the presence or absence of fluid collections and healing tissue planes during the postoperative process. Study data and all adverse events were recorded, with HRUS images reviewed by investigators and confirmed by an independent radiologist.

Results

Seventy-one Interi patients were enrolled. Mean age was 43 (range: 21-74) and BMI was 28. Seroma was confirmed clinically and through HRUS in 3/71 patients, and was associated with either clot (2) or failure to activate system (1). Interi's ability to eliminate fluid and approximate/hold surgical tissue planes together was confirmed with HRUS. No other major complications, including abscess, hematomas, or flap necrosis were observed.

Conclusions

This novel Internal Tissue Closure System effectively evacuated blood and fluid, approximated and maintained closure of internal tissue planes in abdominoplasty patients, allowing for primary tissue healing and internal wound closure to occur. Healing tissue planes and any fluid present are easily identified on HRUS visualizing actual internal tissue healing with a simple, widely available radiographic scan.

Level of Evidence: 3
NSF4SL: negative-sample-free contrastive learning for ranking synthetic lethal partner genes in human cancers
Authors: Wang Shike , Feng Yimiao , Liu Xin , Liu Yong , Wu Min , Zheng Jie
Published: September 2022

Motivation

Detecting synthetic lethality (SL) is a promising strategy for identifying anti-cancer drug targets. Targeting SL partners of a primary gene mutated in cancer is selectively lethal to cancer cells. Due to high cost of wet-lab experiments and availability of gold standard SL data, supervised machine learning for SL prediction has been popular. However, most of the methods are based on binary classification and thus limited by the lack of reliable negative data. Contrastive learning can train models without any negative sample and is thus promising for finding novel SLs.

Results

We propose NSF4SL, a negative-sample-free SL prediction model based on a contrastive learning framework. It captures the characteristics of positive SL samples by using two branches of neural networks that interact with each other to learn SL-related gene representations. Moreover, a feature-wise data augmentation strategy is used to mitigate the sparsity of SL data. NSF4SL significantly outperforms all baselines which require negative samples, even in challenging experimental settings. To the best of our knowledge, this is the first time that SL prediction is formulated as a gene ranking problem, which is more practical than the current formulation as binary classification. NSF4SL is the first contrastive learning method for SL prediction and its success points to a new direction of machine-learning methods for identifying novel SLs.

Availability and implementation

Our source code is available at https://github.com/JieZheng-ShanghaiTech/NSF4SL.

Supplementary information

Supplementary data are available at Bioinformatics online.
SALAI-Net: species-agnostic local ancestry inference network
Authors: Oriol Sabat Benet , Mas Montserrat Daniel , Giro-i-Nieto Xavier , Ioannidis Alexander G
Published: September 2022

Motivation

Local ancestry inference (LAI) is the high resolution prediction of ancestry labels along a DNA sequence. LAI is important in the study of human history and migrations, and it is beginning to play a role in precision medicine applications including ancestry-adjusted genome-wide association studies (GWASs) and polygenic risk scores (PRSs). Existing LAI models do not generalize well between species, chromosomes or even ancestry groups, requiring re-training for each different setting. Furthermore, such methods can lack interpretability, which is an important element in each of these applications.

Results

We present SALAI-Net, a portable statistical LAI method that can be applied on any set of species and ancestries (species-agnostic), requiring only haplotype data and no other biological parameters. Inspired by identity by descent methods, SALAI-Net estimates population labels for each segment of DNA by performing a reference matching approach, which leads to an interpretable and fast technique. We benchmark our models on whole-genome data of humans and we test these models’ ability to generalize to dog breeds when trained on human data. SALAI-Net outperforms previous methods in terms of balanced accuracy, while generalizing between different settings, species and datasets. Moreover, it is up to two orders of magnitude faster and uses considerably less RAM memory than competing methods.

Availability and implementation

We provide an open source implementation and links to publicly available data at github.com/AI-sandbox/SALAI-Net. Data is publicly available as follows: https://www.internationalgenome.org (1000 Genomes), https://www.simonsfoundation.org/simons-genome-diversity-project (Simons Genome Diversity Project), https://www.sanger.ac.uk/resources/downloads/human/hapmap3.html (HapMap), ftp://ngs.sanger.ac.uk/production/hgdp/hgdp_wgs.20190516 (Human Genome Diversity Project) and https://www.ncbi.nlm.nih.gov/bioproject/PRJNA448733 (Canid genomes).

Supplementary information

Supplementary data are available from Bioinformatics online.
Discovering significant evolutionary trajectories in cancer phylogenies
Authors: Pellegrina Leonardo , Vandin Fabio
Published: September 2022

Motivation

Tumors are the result of a somatic evolutionary process leading to substantial intra-tumor heterogeneity. Single-cell and multi-region sequencing enable the detailed characterization of the clonal architecture of tumors and have highlighted its extensive diversity across tumors. While several computational methods have been developed to characterize the clonal composition and the evolutionary history of tumors, the identification of significantly conserved evolutionary trajectories across tumors is still a major challenge.

Results

We present a new algorithm, MAximal tumor treeS TRajectOries (MASTRO), to discover significantly conserved evolutionary trajectories in cancer. MASTRO discovers all conserved trajectories in a collection of phylogenetic trees describing the evolution of a cohort of tumors, allowing the discovery of conserved complex relations between alterations. MASTRO assesses the significance of the trajectories using a conditional statistical test that captures the coherence in the order in which alterations are observed in different tumors. We apply MASTRO to data from nonsmall-cell lung cancer bulk sequencing and to acute myeloid leukemia data from single-cell panel sequencing, and find significant evolutionary trajectories recapitulating and extending the results reported in the original studies.

Availability and implementation

MASTRO is available at https://github.com/VandinLab/MASTRO.

Supplementary information

Supplementary data are available at Bioinformatics online.
3CAC: improving the classification of phages and plasmids in metagenomic assemblies using assembly graphs
Authors: Pu Lianrong , Shamir Ron
Published: September 2022

Motivation

Bacteriophages and plasmids usually coexist with their host bacteria in microbial communities and play important roles in microbial evolution. Accurately identifying sequence contigs as phages, plasmids and bacterial chromosomes in mixed metagenomic assemblies is critical for further unraveling their functions. Many classification tools have been developed for identifying either phages or plasmids in metagenomic assemblies. However, only two classifiers, PPR-Meta and viralVerify, were proposed to simultaneously identify phages and plasmids in mixed metagenomic assemblies. Due to the very high fraction of chromosome contigs in the assemblies, both tools achieve high precision in the classification of chromosomes but perform poorly in classifying phages and plasmids. Short contigs in these assemblies are often wrongly classified or classified as uncertain.

Results

Here we present 3CAC, a new three-class classifier that improves the precision of phage and plasmid classification. 3CAC starts with an initial three-class classification generated by existing classifiers and improves the classification of short contigs and contigs with low confidence classification by using proximity in the assembly graph. Evaluation on simulated metagenomes and on real human gut microbiome samples showed that 3CAC outperformed PPR-Meta and viralVerify in both precision and recall, and increased F1-score by 10–60 percentage points.

Availability and implementation

The 3CAC software is available on https://github.com/Shamir-Lab/3CAC.

Supplementary information

Supplementary data are available at Bioinformatics online.
MPVNN: Mutated Pathway Visible Neural Network architecture for interpretable prediction of cancer-specific survival risk
Authors: Ghosh Roy Gourab , Geard Nicholas , Verspoor Karin , He Shan
Published: September 2022

Motivation

Survival risk prediction using gene expression data is important in making treatment decisions in cancer. Standard neural network (NN) survival analysis models are black boxes with a lack of interpretability. More interpretable visible neural network architectures are designed using biological pathway knowledge. But they do not model how pathway structures can change for particular cancer types.

Results

We propose a novel Mutated Pathway Visible Neural Network (MPVNN) architecture, designed using prior signaling pathway knowledge and random replacement of known pathway edges using gene mutation data simulating signal flow disruption. As a case study, we use the PI3K-Akt pathway and demonstrate overall improved cancer-specific survival risk prediction of MPVNN over other similar-sized NN and standard survival analysis methods. We show that trained MPVNN architecture interpretation, which points to smaller sets of genes connected by signal flow within the PI3K-Akt pathway that is important in risk prediction for particular cancer types, is reliable.

Availability and implementation

The data and code are available at https://github.com/gourabghoshroy/MPVNN.

Supplementary information

Supplementary data are available at Bioinformatics online.
BioBulkFoundary: a customized webserver for exploring biosynthetic potentials of bulk chemicals
Authors: Sun Dandan , Ding Shaozhen , Cai Pengli , Zhang Dachuan , Han Mengying , Hu Qian-Nan
Published: September 2022

Advances in metabolic engineering have boosted the production of bulk chemicals, resulting in tons of production volumes of some bulk chemicals with very low prices. A decrease in the production cost and overproduction of bulk chemicals makes it necessary and desirable to explore the potential to synthesize higher-value products from them. It is also useful and important for society to explore the use of design methods involving synthetic biology to increase the economic value of these bulk chemicals. Therefore, we developed ‘BioBulkFoundary’, which provides an elaborate analysis of the biosynthetic potential of bulk chemicals based on the state-of-art exploration of pathways to synthesize value-added chemicals, along with associated comprehensive technology and economic database into a user-friendly framework.

Availability and implementation

Freely available on the web at http://design.rxnfinder.org/biobulkfoundary/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Multilayer Exponential Family Factor models for integrative analysis and learning disease progression
Authors: Wang Qinxia , Wang Yuanjia
Published: September 2022

Current diagnosis of neurological disorders often relies on late-stage clinical symptoms, which poses barriers to developing effective interventions at the premanifest stage. Recent research suggests that biomarkers and subtle changes in clinical markers may occur in a time-ordered fashion and can be used as indicators of early disease. In this article, we tackle the challenges to leverage multidomain markers to learn early disease progression of neurological disorders. We propose to integrate heterogeneous types of measures from multiple domains (e.g., discrete clinical symptoms, ordinal cognitive markers, continuous neuroimaging, and blood biomarkers) using a hierarchical Multilayer Exponential Family Factor (MEFF) model, where the observations follow exponential family distributions with lower-dimensional latent factors. The latent factors are decomposed into shared factors across multiple domains and domain-specific factors, where the shared factors provide robust information to perform extensive phenotyping and partition patients into clinically meaningful and biologically homogeneous subgroups. Domain-specific factors capture remaining unique variations for each domain. The MEFF model also captures nonlinear trajectory of disease progression and orders critical events of neurodegeneration measured by each marker. To overcome computational challenges, we fit our model by approximate inference techniques for large-scale data. We apply the developed method to Parkinson’s Progression Markers Initiative data to integrate biological, clinical, and cognitive markers arising from heterogeneous distributions. The model learns lower-dimensional representations of Parkinson’s disease (PD) and the temporal ordering of the neurodegeneration of PD.
Age-dependent increased sag amplitude in human pyramidal neurons dampens baseline cortical activity
Authors: Guet-McCreight Alexandre , Chameh Homeira Moradi , Mahallati Sara , Wishart Margaret , Tripathy Shreejoy J , Valiante Taufik A , Hay Etay
Published: September 2022

Aging involves various neurobiological changes, although their effect on brain function in humans remains poorly understood. The growing availability of human neuronal and circuit data provides opportunities for uncovering age-dependent changes of brain networks and for constraining models to predict consequences on brain activity. Here we found increased sag voltage amplitude in human middle temporal gyrus layer 5 pyramidal neurons from older subjects and captured this effect in biophysical models of younger and older pyramidal neurons. We used these models to simulate detailed layer 5 microcircuits and found lower baseline firing in older pyramidal neuron microcircuits, with minimal effect on response. We then validated the predicted reduced baseline firing using extracellular multielectrode recordings from human brain slices of different ages. Our results thus report changes in human pyramidal neuron input integration properties and provide fundamental insights into the neuronal mechanisms of altered cortical excitability and resting-state activity in human aging.
Effects of emotional valence and intensity on cognitive and affective empathy after insula lesions
Authors: Holtmann Olga , Schloßmacher Insa , Franz Marcel , Moenig Constanze , Tenberge Jan-Gerd , Preul Christoph , Schwindt Wolfram , Bruchmann Maximilian , Melzer Nico , Miltner Wolfgang H R , Straube Thomas
Published: September 2022

The insula plays a central role in empathy. However, the complex structure of cognitive (CE) and affective empathy (AE) deficits following insular damage is not fully understood. In the present study, patients with insular lesions (n = 20) and demographically matched healthy controls (n = 24) viewed ecologically valid videos that varied in terms of valence and emotional intensity. The videos showed a person (target) narrating a personal life event. In CE conditions, subjects continuously rated the affective state of the target, while in AE conditions, they continuously rated their own affect. Mean squared error (MSE) assessed deviations between subject and target ratings. Patients differed from controls only in negative, low-intensity AE, rating their own affective state less negative than the target. This deficit was not related to trait empathy, neuropsychological or clinical parameters, or laterality of lesion. Empathic functions may be widely spared after insular damage in a naturalistic, dynamic setting, potentially due to the intact interpretation of social context by residual networks outside the lesion. The particular role of the insula in AE for negative states may evolve specifically in situations that bear higher uncertainty pointing to a threshold role of the insula in online ratings of AE.
CCESHP: Causal Consistency Model of Edge Storage Based on Hash Ring and Partial Geo-Replication
Authors: Tian Junfeng , Jia Haoyi , Bai Wenqing
Published: September 2022

At present, most of the causal consistency models that rely on cloud storage have problems such as high operation delays and large metadata overhead. To solve these problems, this paper proposes a causal consistency model for edge storage based on hash rings, CCESHP. The proposed model uses two hashes to map the keys and servers on the hash ring for grouping and stores a subset of the complete data set in a replica node located at the edge of the network, thereby realizing a partial geographic replication strategy in the edge storage environment. Operation latency will be reduced since the edge replica is closer to the client. At the same time, it also generates and maintains a combined timestamp to capture causality according to the update type, which can keep the amount of managed metadata in a relatively stable and low state, reduce the overhead of system management metadata, and improve system throughput. The experimental evaluation results under different workloads show that the model has better performance in throughput and operation delay when compared with the existing causal consistency model.
Single-center experience in implementation of endoscopic surveillance protocol after esophagectomy
Authors: Kamaludin Ahmad , Donlon Noel E , Kavanagh Matthew , Reynolds John V , Donohoe Claire L
Published: September 2022

Esophageal cancer has a notably high recurrence rate with a paucity of robust evidence in defining the optimal surveillance strategy. The surveillance protocol at our institution comprises of annual esophagogastroduodenoscopy (OGD) from years 1 to 5 postoperatively. This study aims to evaluate the implementation of the endoscopic surveillance at our center and ascertain the value of endoscopy in detecting local recurrence after esophagectomy. A retrospective cohort review of all patients (320 patients) who underwent esophagectomy between 2013 and 2018 was conducted. The local esophageal cancer database and corresponding OGD reports were accessed to obtain data on demographics, operation details, local recurrence, and endoscopy performed. 1086 OGDs were performed between 2014 and 2020, broadly categorized to surveillance and symptomatic OGDs; 555 and 531, respectively. Surveillance OGDs detected four asymptomatic local recurrences, of which only one was treated with curative intent. Symptomatic OGDs resulted in a higher yield for the detection of local recurrence compared with surveillance endoscopy; 5% versus 0.7%, with overall median time-to-recurrence of 11.5 months (95% confidence interval 9–17). Of local recurrences, 85.7% occurred within the first 2 years postoperatively. The proportion of endoscopic findings differed between intensive and ad hoc surveillance cohorts for strictures, esophagitis, Barrett’s esophagus, and sloughing. Thirteen patients were diagnosed with histologically confirmed Barrett’s with no subsequent local recurrences. Surveillance endoscopy had a low positive yield rate with subsequent minimal survival benefits. Therefore, it is prudent to consider an alternative protocol that focuses on the period with the highest risk of recurrence and symptom presentation.
Disease Activity Patterns of Inflammatory Bowel Disease—A Danish Nationwide Cohort Study 1995–2018
Authors: Wewer Mads Damsgaard , Langholz Ebbe , Munkholm Pia , Bendtsen Flemming , Benedict Seidelin Jakob , Burisch Johan
Published: September 2022

Background and Aims

Few studies have assessed the contemporary patterns of disease activity in patients with inflammatory bowel disease [IBD]. We aimed to describe the disease patterns and their long-term outcomes.

Methods

All Danish individuals with IBD between 1995 and 2018 were identified using information about IBD-related hospitalizations, surgeries and redeemed prescriptions. The disease activity patterns for 5- and 10-year periods were assessed.

Results

In incident patients with Crohn’s disease [CD], severe disease activity occurred in the year of diagnosis in 80% of patients; for ulcerative colitis [UC] this figure was 75%, in addition to 3.4% of UC patients who underwent a colectomy within the first year. After 20 years of disease, the proportion of CD and UC patients in remission increased to 89% and 72%, respectively. The proportion of prevalent patients in remission each year was stable, despite the introduction of biological therapies. A decreasing activity pattern was the most common in both CD and UC patients [both 45%]. The distribution of the disease activity patterns was seen to be stable over time. A quiescent disease pattern was accompanied by a significantly higher risk of intestinal cancer [HR: 3.37, 95% CI: 1.23–9.19] for CD patients, according to a Cox proportional hazards model. In UC patients, increasing disease activity [HR: 0.67, 95% CI: 0.31–1.48] was associated with an increased risk of intestinal cancer.

Conclusions

We report the distribution of disease patterns among IBD patients. Patients with quiescent CD, as well as UC patients with chronic continuous or increasing activity, were at increased risk of developing intestinal cancer.