bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring long-term exposure to wildfire PM
2.5
in California: Time-varying inequities in environmental burden
Authors: Casey Joan A. , Kioumourtzoglou Marianthi-Anna , Padula Amy , González David J. X. , Elser Holly , Aguilera Rosana , Northrop Alexander J. , Tartof Sara Y. , Mayeda Elizabeth Rose , Braun Danielle , Dominici Francesca , Eisen Ellen A. , Morello-Frosch Rachel , Benmarhnia Tarik
Published: February 2024

Wildfires have become more frequent and intense due to climate change and outdoor wildfire fine particulate matter (PM
2.5
) concentrations differ from relatively smoothly varying total PM
2.5
. Thus, we introduced a conceptual model for computing long-term wildfire PM
2.5
and assessed disproportionate exposures among marginalized communities. We used monitoring data and statistical techniques to characterize annual wildfire PM
2.5
exposure based on intermittent and extreme daily wildfire PM
2.5
concentrations in California census tracts (2006 to 2020). Metrics included: 1) weeks with wildfire PM
2.5
> 5 μg/m
3
; 2) days with non-zero wildfire PM
2.5
; 3) mean wildfire PM
2.5
during peak exposure week; 4) smoke waves (≥2 consecutive days with >15 μg/m
3
wildfire PM
2.5
); and 5) mean annual wildfire PM
2.5
concentration. We classified tracts by their racial/ethnic composition and CalEnviroScreen (CES) score, an environmental and social vulnerability composite measure. We examined associations of CES and racial/ethnic composition with the wildfire PM
2.5
metrics using mixed-effects models. Averaged 2006 to 2020, we detected little difference in exposure by CES score or racial/ethnic composition, except for non-Hispanic American Indian and Alaska Native populations, where a 1-SD increase was associated with higher exposure for 4/5 metrics. CES or racial/ethnic × year interaction term models revealed exposure disparities in some years. Compared to their California-wide representation, the exposed populations of non-Hispanic American Indian and Alaska Native (1.68×, 95% CI: 1.01 to 2.81), white (1.13×, 95% CI: 0.99 to 1.32), and multiracial (1.06×, 95% CI: 0.97 to 1.23) people were over-represented from 2006 to 2020. In conclusion, during our study period in California, we detected disproportionate long-term wildfire PM
2.5
exposure for several racial/ethnic groups.
Enhanced charge-carrier dynamics and efficient solar-to-urea conversion on Si-based photocathodes
Authors: Zhang Xiaoran , Lyu Yanhong , Chen Chen , Zheng Jianyun , Jiang San Ping , Wang Shuangyin
Published: February 2024

Photoelectrochemical (PEC) coupling of CO
2
and nitrate can provide a useful and green source of urea, but the process is affected by the photocathodes with poor charge-carrier dynamics and low conversion efficiency. Here, a NiFe diatomic catalysts/TiO
2
layer/nanostructured n
+
p-Si photocathode is rationally designed, achieving a good charge-separation efficiency of 78.8% and charge-injection efficiency of 56.9% in the process of PEC urea synthesis. Compared with the electrocatalytic urea synthesis by using the same catalysts, the Si-based photocathode shows a similar urea yield rate (81.1 mg·h
−1
·cm
−2
) with a higher faradic efficiency (24.2%, almost twice than the electrocatalysis) at a lower applied potential under 1 sun illumination, meaning that a lower energy-consumption method acquires more aimed productions. Integrating the PEC measurements and characterization results, the synergistic effect of hierarchical structure is the dominating factor for enhancing the charge-carrier separation, transfer, and injection by the matched band structure and favorable electron-migration channels. This work provides a direct and efficient route of solar-to-urea conversion.
Metabolism of host lysophosphatidylcholine in
Plasmodium falciparum
–infected erythrocytes
Authors: Liu Jiapeng , Fike Katherine R. , Dapper Christie , Klemba Michael
Published: February 2024

The human malaria parasite
Plasmodium falciparum
requires exogenous fatty acids to support its growth during the pathogenic, asexual erythrocytic stage. Host serum lysophosphatidylcholine (LPC) is a significant fatty acid source, yet the metabolic processes responsible for the liberation of free fatty acids from exogenous LPC are unknown. Using an assay for LPC hydrolysis in
P. falciparum
–infected erythrocytes, we have identified small-molecule inhibitors of key in situ lysophospholipase activities. Competitive activity-based profiling and generation of a panel of single-to-quadruple knockout parasite lines revealed that two enzymes of the serine hydrolase superfamily, termed exported lipase (XL) 2 and exported lipase homolog (XLH) 4, constitute the dominant lysophospholipase activities in parasite-infected erythrocytes. The parasite ensures efficient exogenous LPC hydrolysis by directing these two enzymes to distinct locations: XL2 is exported to the erythrocyte, while XLH4 is retained within the parasite. While XL2 and XLH4 were individually dispensable with little effect on LPC hydrolysis in situ, loss of both enzymes resulted in a strong reduction in fatty acid scavenging from LPC, hyperproduction of phosphatidylcholine, and an enhanced sensitivity to LPC toxicity. Notably, growth of XL/XLH-deficient parasites was severely impaired when cultured in media containing LPC as the sole exogenous fatty acid source. Furthermore, when XL2 and XLH4 activities were ablated by genetic or pharmacologic means, parasites were unable to proliferate in human serum, a physiologically relevant fatty acid source, revealing the essentiality of LPC hydrolysis in the host environment and its potential as a target for anti-malarial therapy.
The World of Daily Life
Authors: Rasmussen Gitte , Kristiansen Elisabeth , Poulsen Søren Vigild
Published: February 2024

Within social scientific research searching for products is overwhelmingly reduced and represented as an activity that is embedded in decision-making processes. This study shows that searching is extremely multimodally rich and complex and that structured stages of searching are the product of customers’ efforts to order this complexity in and through concrete actions. Importantly, it also shows that customers carry out these actions un-hesitantly in both physical Brick-and Mortar (B&M) shops and in web-shops. The paper concludes that descriptions of searching need to take the nature of the multimodal environment as well as customers’ approach and engagement with it into consideration: searching for products is multimodally rich and complex and yet it is simple.

The study is situated within the broad fields of EMCA and Social Semiotics in multimodality. It is based on video-recordings and eye‑tracking recordings of customers’ buying practices in different kinds of (web)shops.
Los puertorriqueños se les está cayendo la “a”
Authors: Vélez Avilés Jessica
Published: February 2024

This study addresses a gap in the extensive literature on Spanish indirect objects by offering a study of unmarked
datives (i.e.,
Ø eso le pones un papel de aluminio ‘to that you put
an aluminum foil’; PRESEEA 2001). Analyzed are the linguistic constraints on the
variable absence of dative marker a ‘to’ in corpora of spoken Puerto Rican Spanish, in which the rate of marker
absence is 33% (n = 380). Results of logistic regression analysis reveal that unmarked datives occurred with low
frequency, non-prototypical dative verbs. Inanimate referents favored the absence of the dative marker, as did complex DPs, where
the dative phrase and the clitic pronoun+verb are not adjacent. The findings are discussed from the twin perspectives of analogy
as a mechanism of change and frequency effects: unmarked datives seem to most affect items at the margins of the dative category,
in terms of both verbs and referents.
Impact of technical and operational factors on effectiveness of automatic load-haul-dump machines
Authors: Gustafson Anna , Paraszczak Jacek , Tuleau Jocelyn , Schunnesson Håkan
Published: February 2024

The use of automatic load-haul-dump (LHD) machines in underground metal mines is a promising way to overcome some of the challenges now facing mining companies. They offer several potential benefits over man-operated units, mostly in terms of safety and health of the workers, but also in terms of higher availability, increased productivity, and reduced mining cost. That said, using such systems at their full capacity is a challenging and complex task. In this context, after describing some commercially available equipment and systems, the paper examines factors affecting reliability, availability and productivity of automatic LHDs and notes several technical and operational concerns.
Microwave time reversal for nondestructive testing of buried small damage in composite materials
Authors: An Kang , Li Changyou , Long Guoqian , Ding Jun
Published: February 2024

Composite materials are widely applied in aerospace, civil engineering, and sports equipment. Various damages produced during fabrication and long-term use can destroy its original mechanical properties, which brings safety and structural healthy concerns. Microwave imaging based on time reversal (TR) is one of the most promising nondestructive testing methods for portable, low-cost, and accurate testing with the advantages of auto-focus and super-resolution. This paper applied microwave TR for the detection of buried small damage in composites backed by metal plates. Strong reflection from composite–metal interfaces brings challenges in successfully achieving time-reversal auto-focusing on small and weak-scattering damages in composites. Traditional target localization methods, including the entropy regularization method and time-integrated energy method, may result in the wrong localization of small damages. The main contribution of this paper is that the localization problem caused by the strong reflection from metal plates is revealed first, and the target initial reflection method from through-wall-radar imaging is introduced to solve it. The performance of three target localization methods is investigated, and the physical reasons for failure or successful localization are discussed in detail. Some performance influence factors, such as the arrangement of receivers or the total time step of received signals, are also discussed. Good performance for the detection of a single small damage with a weak scattered signal is achieved, and the performance for detecting multiple damages is studied. All time-reversal simulations are carried out based on the finite-difference time-domain method.
Passive communication for low power distributed sensors using MEMS optical cavities
Authors: Schopp Jacob , McNamara Shamus
Published: February 2024

Distributed sensing has been of great interest in recent research. Distributed sensors are in part defined by the methods they use to communicate. We demonstrate a new low power method of optical communication. Instead of communicating optically by generating new light to communicate using a light emitting diode or laser, our method uses optical interference to vary the reflectivity of a micro-electromechanical systems (MEMS) optical cavity. A thin air gap between an adjustable MEMS mirror made on a silicon on insulator die and glass encapsulation generates optical interference. By moving the mirror electrostatically, the reflected light intensity is modulated, and signals are transmitted passively. The transmitted signal is measured by observing the reflected light intensity with a photodiode. We demonstrate the use of fiber optic cables to deliver illumination and collect reflected light with modulated intensity. We propose that these devices may also be used in series arrays where reflected light from one optical cavity can be used as illumination for another.
Controlling the charge of dust particles in an afterglow by modulating the plasma power
Authors: Chaubey Neeraj , Goree J
Published: February 2024

A dust particle immersed in a glow-discharge plasma has long been known to have a charge that is negative, while the plasma is powered. However, in the afterglow, following the stopping of the plasma power, a large positive charge can collect on the particle, as was shown recently for particles in a cathodic sheath. While that outcome of positive charging in the afterglow may be common, an experimental discovery reported here reveals that the opposite outcome is also possible: a particle can develop a negative charge in the afterglow, if the plasma had previously been operated with a modulated power. Before stopping the plasma power off altogether, in a run with power modulated at a low duty cycle of 4.5

%

, the particle’s residual charge was negative, but it was positive in a control run without modulation. This result points to a way of controlling the charge of dust particles in a decaying plasma, which can be useful for mitigating defects in semiconductor manufacturing.
A meta-learning method for few-shot bearing fault diagnosis under variable working conditions
Authors: Zeng Liang , Jian Junjie , Chang Xinyu , Wang Shanshan
Published: February 2024

Intelligent fault diagnosis in various industrial applications has rapidly evolved due to the recent advancements in data-driven techniques. However, the scarcity of fault data and a wide range of working conditions pose significant challenges for existing diagnostic algorithms. This study introduces a meta-learning method tailored for the classification of motor rolling bearing faults, addressing the challenges of limited data and diverse conditions. In this approach, a deep residual shrinkage network is employed to extract salient features from bearing vibration signals. These features are then analyzed in terms of their proximity to established fault prototypes, enabling precise fault categorization. Moreover, the model’s generalization in few-shot scenarios is enhanced through the incorporation of a meta-learning paradigm during training. The approach is evaluated using two well-known public bearing datasets, focusing on varying speeds, loads, and high noise environments. The experimental results indicate the superior diagnostic accuracy and robustness of our method compared with those of existing studies.
Modeling the interplay of oscillatory synchronization and aggregation via cell–cell adhesion
Authors: Glimm Tilmann , Gruszka Daniel
Published: February 2024

We present a model of systems of cells with intracellular oscillators (‘clocks’). This is motivated by examples from developmental biology and from the behavior of organisms on the threshold to multicellularity. Cells undergo random motion and adhere to each other. The adhesion strength between neighbors depends on their clock phases in addition to a constant baseline strength. The oscillators are linked via Kuramoto-type local interactions. The model is an advection-diffusion partial differential equation with nonlocal advection terms. We demonstrate that synchronized states correspond to Dirac-delta measure solutions of a weak version of the equation. To analyze the complex interplay of aggregation and synchronization, we then perform a linear stability analysis of the incoherent, spatially uniform state. This lets us classify possibly emerging patterns depending on model parameters. Combining these results with numerical simulations, we determine a range of possible far-from equilibrium patterns when baseline adhesion strength is zero: There is aggregation into separate synchronized clusters with or without global synchrony; global synchronization without aggregation; or unexpectedly a ‘phase wave’ pattern characterized by spatial gradients of clock phases. A 2D Lattice-Gas Cellular Automaton model confirms and illustrates these results.
Unsupervised ensembling of multiple software sensors with phase synchronization: a robust approach for electrocardiogram-derived respiration
Authors: McErlean Jacob , Malik John , Lin Yu-Ting , Talmon Ronen , Wu Hau-Tieng
Published: February 2024

Objective. We aimed to fuse the outputs of different electrocardiogram-derived respiration (EDR) algorithms to create one higher quality EDR signal. Methods. We viewed each EDR algorithm as a software sensor that recorded breathing activity from a different vantage point, identified high-quality software sensors based on the respiratory signal quality index, aligned the highest-quality EDRs with a phase synchronization technique based on the graph connection Laplacian, and finally fused those aligned, high-quality EDRs. We refer to the output as the sync-ensembled EDR signal. The proposed algorithm was evaluated on two large-scale databases of whole-night polysomnograms. We evaluated the performance of the proposed algorithm using three respiratory signals recorded from different hardware sensors, and compared it with other existing EDR algorithms. A sensitivity analysis was carried out for a total of five cases: fusion by taking the mean of EDR signals, and the four cases of EDR signal alignment without and with synchronization and without and with signal quality selection. Results. The sync-ensembled EDR algorithm outperforms existing EDR algorithms when evaluated by the synchronized correlation (

γ

-score), optimal transport (OT) distance, and estimated average respiratory rate score, all with statistical significance. The sensitivity analysis shows that the signal quality selection and EDR signal alignment are both critical for the performance, both with statistical significance. Conclusion. The sync-ensembled EDR provides robust respiratory information from electrocardiogram. Significance. Phase synchronization is not only theoretically rigorous but also practical to design a robust EDR.
First measurements with a Coherence Imaging Charge Exchange Recombination Spectroscopy (CICERS) diagnostic at Wendelstein 7-X
Authors: Lopez-Cansino R , Perseo V , Viezzer E , Kriete D M , Ford O P , Romba T , Poloskei P Zs ,   the W7-X Team
Published: February 2024

In this work, the Coherence Imaging Spectroscopy technique is exploited for active charge exchange radiation measurements to infer high spatial resolution 2D ion temperature (

T

i

) maps in the core region of Wendelstein 7-X plasmas. A synthetic model of the diagnostic is developed and used for the optimization of the hardware components for the expected ion temperatures (

T

i

∼
2

 keV) prioritizing

T

i

measurements while also considering the ion velocity flow resolution. The experimental set-up is shown and the diagnostic calibration procedure for

T

i

measurements is introduced. A combination of both simulations and experimental calibrations enable high fidelity system group delay (

∂
ϕ

∂
λ

) characterization in the whole visible spectral range. Finally, the signal processing techniques applied to the diagnostic signal are introduced and first measurements of 2D

T

i

maps are presented and validated against standard Charge eXchange Recombination Spectroscopy

T

i

profiles, finding excellent agreement.
Insights on seasonal solifluction processes in warm permafrost Arctic landscape using a dense monitoring approach across adjacent hillslopes
Authors: Fiolleau Sylvain , Uhlemann Sebastian , Shirley Ian A , Wang Chen , Wielandt Stijn , Rowland Joel , Dafflon Baptiste
Published: February 2024

Solifluction processes in the Arctic are highly complex, introducing uncertainties in estimating current and future soil carbon storage and fluxes, and assessment of hillslope and infrastructure stability. This study aims to enhance our understanding of triggers and drivers of soil movement of permafrost-affected hillslopes in the Arctic. To achieve this, we established an extensive soil deformation and temperature sensor network, covering 48 locations across multiple hillslopes within a 1 km² watershed on the Seward Peninsula, AK. We report depth-resolved measurements down to 1.8 m depth for May to September 2022, a period conducive to soil movement due to deepening thaw layers and frequent rain events. Over this period, surface movements of up to 334 mm were recorded. In general, these movements occur close to the thawing front, and are initiated as thawing reaches depths of 0.4 to 0.75 m. The largest movements were observed at the top of the south-east facing slope, where soil temperatures are cold (mean annual soil temperatures averaging -1.13°C) and slopes are steeper than 15°. Our analysis highlights three primary factors influencing movements: slope angle, soil thermal conditions, and thaw depth. The latter two significantly impact the generation of pore water pressures at the thaw–freeze interface. Specifically, soil thermal conditions govern the liquid water content, while thaw depth influences both the height of the water column and, consequently, the pressure at the thawing front. These factors affect soil properties, such as cohesion and internal friction angle, which are crucial determinants of slope stability. This underscores the significance of a precise understanding of subsurface thermal conditions, including spatial and temporal variability in soil temperature and thaw depth, when assessing and predicting slope instabilities. Based on our observations, we developed a Factor of Safety proxy that consistently falls below the triggering threshold for all probes exhibiting displacements exceeding 50 mm. This study offers novel insights into patterns and triggers of hillslope movements in the Arctic and provides a venue to evaluate their impact on soil redistribution.
Branching laws for spherical harmonics on superspaces in exceptional cases
Authors: Lávička Roman
Published: February 2024

It turns out that harmonic analysis on the superspace

R

m

|

2
n

is quite parallel to the classical theory on the Euclidean space

R

m

unless the superdimension

M
:=
m
−
2
n

is even and non-positive. The underlying symmetry is given by the orthosymplectic superalgebra

o
s
p

(
m

|

2
n
)

. In this paper, when the symmetry is reduced to

o
s
p

(
m
−
1

|

2
n
)

we describe explicitly the corresponding branching laws for spherical harmonics on

R

m

|

2
n

also in exceptional cases, i.e, when

M
−
1
∈
−
2

N

0

. In unexceptional cases, these branching laws are well-known and quite analogous as in the Euclidean framework.
Revisiting anapoles in a single high-index dielectric structure
Authors: Wang Longxiao , Huang Lujun
Published: February 2024

High-index dielectric structures support electric and magnetic Mie resonance. Through careful manipulation of geometric parameters, destructive interference can be induced between electric multipole moments and toroidal multipole moments. This leads to the formation of anapoles, which are characterized by quenched scattering in the far field and giant enhancement in the near field. Here, we revisit the formation mechanism of anapole states in a single dielectric structure with a high refractive index from an eigenmode perspective. We find that scattering efficiency is mainly determined by the intrinsic phase governed by the leaky mode of the structure and the extrinsic phase induced by the frequency deviation from resonance. It is also demonstrated that the anapole modes in a two-dimensional cylinder and a three-dimensional sphere can only occur in the following two situations: (1) when only one mode is involved, the combined phase of intrinsic and extrinsic phase should be equal to 2π at a certain frequency (anapole frequency), which is very close to the resonance frequency. Generally, these types of anapoles are low-order anapoles since low-order resonant modes (i.e., magnetic (electric) dipole and quadrupole) are well separated. (2) If two or more leaky modes are involved, the combined phase for each mode must be 2π at the same frequency located between the two resonances. This corresponds to the high-order anapoles. It is also found that more anapole states will emerge with increasing refractive index. Our results may provide new perspectives for designing high-order anapoles with more freedom.
Bandgap engineering and amplification in photonic time crystals
Authors: Sadhukhan Snehashis , Ghosh Somnath
Published: February 2024

Recently, there has been a growing interest in time-varying photonic media owing to their significant potential in the field of wave manipulation. Here, we explore the exotic characteristics of wave amplification in a photonic time crystal (PTC) made of a spatially homogeneous medium where the refractive index varies periodically in time. Based on qualitative and quantitative analysis of the amplification, we show that the amplification not only depends on the choice of wave vector of a propagating light but also attains different values in different bandgaps. Our approach further extends towards achieving the minimum amount of variation of permittivity required to open momentum gaps to facilitate the phase-dependent amplification of PTCs. Further, we investigate the impact of permittivity variation and choice of number of temporal unit cells to truncate a PTC to mimic the properties of infinite PTC and offer new opportunities to manipulate and control the amplification of light for applications including highly tunable PTC lasers and devices.
Parity-time imbalance induced by balanced gain and loss medium in non-Hermitian photonic crystals
Authors: Wang Qianxing , Liu Bobo , Ying Lei
Published: February 2024

Photonic crystals, including gain and loss materials, show numerous intriguing features than the ordinary photonic crystals. In this work, using the full wave simulation, we numerically investigate the photonic crystals with gain and loss which are satisfying the parity-time (PT) symmetry condition to reveal the effect of PT symmetry on the optical properties of photonic crystals, including the exceptional point, distribution of electromagnetic fields and edge states. This work reveals a novel mechanism of coexistence and competition between topological states and non-Hermiticity in all-dielectric photonic crystals and provides an innovative understanding of non-Hermiticity in topological photonic systems.
Compact and efficient lossy mode resonant refractive index sensor for aqueous environment
Authors: Sharma Vinod K
Published: February 2024

A very short length high sensitivity, large figure of merit and very high resolution integrated-photonic refractometer for aqueous environment operating in visible region of wavelength is proposed. The sensor design depends on the periodic coupling of the guided dielectric optical waveguide mode field and the lossy mode field of the conducting indium-tin-oxide thin film. Various layer thicknesses can be optimized to provide power transfer to the lossy layer and lossy mode resonance, resulting in a strong guided mode power absorption in the lossy layer occurs. The sensor has been designed to operate in both the TE and TM polarizations with different optimized layer frthicknesses. The optimized thicknesses are different for TE and TM polarizations. The obtained numerical results show that a spectral sensitivity of 2200 nm/RIU/2645 nm/RIU for TE/TM mode could be achieved with a very high resolution. Also, the sensors can operate in power interrogation mode with a maximum sensitivity nearly 5 × 107 dB RIU−1.
A review of fetal cell lines used during drug development: Focus on COVID-19 vaccines, transplant medications, and biologics
Authors: Durant Karin M , Whitesell Ashlyn , Dasse Kathy D
Published: February 2024

Purpose

The recent coronavirus disease 2019 (COVID-19) pandemic and vaccine mandates have increased the number of patient questions related to how fetal cell lines are used during drug development and final manufacturing. This article describes our literature search and review of COVID-19 vaccines, transplant medications, and biologics whose development included use of fetal cell lines.

A detailed literature search was conducted to identify the common fetal cell lines used in COVID-19 vaccine development; the two most prevalent fetal cell lines identified were HEK-293 and PER.C6. Subsequent literatures searches were conducted to identify transplant medications and biologics whose development included use of the HEK-293 or PER.C6 cell lines. For the COVID-19 vaccines, only the viral vector vaccine by Janssen was found to contain proteins produced by PER.C6 in the final preparation administered to patients, and Novavax is the only vaccine for which fetal cell lines were not directly involved in any portion of drug development. For transplant medications, many medications were studied in fetal cell lines in postmarketing studies after Food and Drug Administration approval; however, none of these medications contained fetal cells or would expose a patient to a fetal cell line. Many new biologics and cellular therapies for genetic diseases and malignancies have been directly developed from HEK-293 fetal cells or contain proteins produced directly from fetal cell lines.

Conclusion

There were very few drugs reviewed that were found to contain HEK-293 or PER.C6 fetal cells or proteins derived directly from fetal cell lines; however, use of fetal cell lines in biologics and gene therapies will continue to increase. Healthcare providers should be mindful of patients’ beliefs while also correcting common misconceptions about how these fetal cell lines are used throughout drug development and manufacturing.
Self-supervised deep learning of gene–gene interactions for improved gene expression recovery
Authors: Wei Qingyue , Islam Md Tauhidul , Zhou Yuyin , Xing Lei
Published: February 2024

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to gain biological insights at the cellular level. However, due to technical limitations of the existing sequencing technologies, low gene expression values are often omitted, leading to inaccurate gene counts. Existing methods, including advanced deep learning techniques, struggle to reliably impute gene expressions due to a lack of mechanisms that explicitly consider the underlying biological knowledge of the system. In reality, it has long been recognized that gene–gene interactions may serve as reflective indicators of underlying biology processes, presenting discriminative signatures of the cells. A genomic data analysis framework that is capable of leveraging the underlying gene–gene interactions is thus highly desirable and could allow for more reliable identification of distinctive patterns of the genomic data through extraction and integration of intricate biological characteristics of the genomic data. Here we tackle the problem in two steps to exploit the gene–gene interactions of the system. We first reposition the genes into a 2D grid such that their spatial configuration reflects their interactive relationships. To alleviate the need for labeled ground truth gene expression datasets, a self-supervised 2D convolutional neural network is employed to extract the contextual features of the interactions from the spatially configured genes and impute the omitted values. Extensive experiments with both simulated and experimental scRNA-seq datasets are carried out to demonstrate the superior performance of the proposed strategy against the existing imputation methods.
Regression analysis of group-tested current status data
Authors: Li Shuwei , Hu Tao , Wang Lianming , McMahan Christopher S , Tebbs Joshua M
Published: February 2024

Group testing is an effective way to reduce the time and cost associated with conducting large-scale screening for infectious diseases. Benefits are realized through testing pools formed by combining specimens, such as blood or urine, from different individuals. In some studies, individuals are assessed only once and a time-to-event endpoint is recorded, for example, the time until infection. Combining group testing with this type of endpoint results in group-tested current status data (Petito & Jewell, 2016). To analyse these complex data, we propose methods that estimate a proportional hazard regression model based on test outcomes from measuring the pools. A sieve maximum likelihood estimation approach is developed that approximates the cumulative baseline hazard function with a piecewise constant function. To identify the sieve estimator, a computationally efficient expectation-maximization algorithm is derived by using data augmentation. Asymptotic properties of both the parametric and nonparametric components of the sieve estimator are then established by applying modern empirical process theory. Numerical results from simulation studies show that our proposed method performs nominally and has advantages over the corresponding estimation method based on individual testing results. We illustrate our work by analysing a chlamydia dataset collected by the State Hygienic Laboratory at the University of Iowa.
Methodologies for smellwalks and scentwalks—a critical review
Authors: Parker Murray , Spennemann Dirk H R , Bond Jennifer
Published: February 2024

Olfactory elements of the human environment are essential with respect to culture, society, and heritage, and robust methodological approaches are necessary to identify and describe aspects of this sensory component. To accurately investigate and advance knowledge of olfactory composition of spaces and places, that is, a smellscape—an olfactory contextualized landscape—innovative methodologies such as smellwalks can be employed as part of the research approach. Despite the increasing use of smellwalks, there is no current standard methodology for this investigative method in practice.

We identify major themes including variance of group size, participant versus researcher-led walking techniques, reinvention of smellwalking process, and methodological discussion and theory. Limitations and future research potential are suggested, including that of group dynamics, attribute focus, the extension of smellwalk attribute data beyond traditional hedonic attributes, and avenues for development of future processes and protocols for multisensory sensewalks.
The Effects of Human Immunodeficiency Virus Type 1 (HIV-1) Antigen-Expanded Specific T-Cell Therapy and Vorinostat on Persistent HIV-1 Infection in People With HIV on Antiretroviral Therapy
Authors: Gay Cynthia L , Hanley Patrick J , Falcinelli Shane D , Kuruc JoAnn D , Pedersen Susan M , Kirchherr Jennifer , Raines Samuel L M , Motta Cecilia M , Lazarski Chris , Chansky Pamela , Tanna Jay , Shibli Abeer , Datar Anushree , McCann Chase D , Sili Uluhan , Ke Ruian , Eron Joseph J , Archin Nancie , Goonetilleke Nilu , Bollard Catherine M , Margolis David M
Published: February 2024

Background

The histone deacetylase inhibitor vorinostat (VOR) can reverse human immunodeficiency virus type 1 (HIV-1) latency in vivo and allow T cells to clear infected cells in vitro. HIV-specific T cells (HXTCs) can be expanded ex vivo and have been safely administered to people with HIV (PWH) on antiretroviral therapy.

Methods

Six PWH received infusions of 2 × 107 HXTCs/m² with VOR 400 mg, and 3 PWH received infusions of 10 × 107 HXTCs/m² with VOR. The frequency of persistent HIV by multiple assays including quantitative viral outgrowth assay (QVOA) of resting CD4+ T cells was measured before and after study therapy.

Results

VOR and HXTCs were safe, and biomarkers of serial VOR effect were detected, but enhanced antiviral activity in circulating cells was not evident. After 2 × 107 HXTCs/m² with VOR, 1 of 6 PWH exhibited a decrease in QVOA, and all 3 PWH exhibited such declines after 10 × 107 HXTCs/m² and VOR. However, most declines did not exceed the 6-fold threshold needed to definitively attribute decline to the study intervention.

Conclusions

These modest effects provide support for the strategy of HIV latency reversal and reservoir clearance, but more effective interventions are needed to yield the profound depletion of persistent HIV likely to yield clinical benefit.

Clinical Trials Registration. NCT03212989.
An integrated method for targeted Oxford Nanopore sequencing and automated bioinformatics for the simultaneous detection of bacteria, fungi, and ARG
Authors: Kuruwa Sanjana , Zade Amrutraj , Shah Sanchi , Moidu Rameez , Lad Shailesh , Chande Chhaya , Joshi Ameeta , Hirani Nilma , Nikam Chaitali , Bhattacharya Sanjay , Poojary Aruna , Kapoor Mahua , Kondabagil Kiran , Chatterjee Anirvan
Published: February 2024

Aims

The use of metagenomics for pathogen identification in clinical practice has been limited. Here we describe a workflow to encourage the clinical utility and potential of NGS for the screening of bacteria, fungi, and antimicrobial resistance genes (ARGs).

Methods and results

The method includes target enrichment, long-read sequencing, and automated bioinformatics. Evaluation of several tools and databases was undertaken across standard organisms (n = 12), clinical isolates (n = 114), and blood samples from patients with suspected bloodstream infections (n = 33). The strategy used could offset the presence of host background DNA, error rates of long-read sequencing, and provide accurate and reproducible detection of pathogens. Eleven targets could be successfully tested in a single assay. Organisms could be confidently identified considering ≥60% of best hits of a BLAST-based threshold of e-value 0.001 and a percent identity of >80%. For ARGs, reads with percent identity of >90% and >60% overlap of the complete gene could be confidently annotated. A kappa of 0.83 was observed compared to standard diagnostic methods. Thus, a workflow for the direct-from-sample, on-site sequencing combined with automated genomics was demonstrated to be reproducible.

Conclusion

NGS-based technologies overcome several limitations of current day diagnostics. Highly sensitive and comprehensive methods of pathogen screening are the need of the hour. We developed a framework for reliable, on-site, screening of pathogens.
Co-occurrence of blaNDM-1 and blaOXA-23 in carbapenemase-producing Acinetobacter baumannii belonging to high-risk lineages isolated from burn patients in Tunisia
Authors: Raddaoui Anis , Mabrouk Aymen , Chebbi Yosra , Frigui Siwar , Salah Abbassi Mohamed , Achour Wafa , Thabet Lamia
Published: February 2024

Aims

Carbapenem-resistant Acinetobacter baumannii (CR-Ab) is an important cause of infections in burn patients. This study aimed to characterize the antimicrobial susceptibility pattern of CR-Ab isolated from burns in Burn Intensive Care Unit (BICU) of the Trauma and Burn Centre of Ben Arous, to determine the prevalence of β-lactamase-encoding genes and to search eventual genetic relatedness of CR-Ab strains.

Methods and Results

From 15 December 2016 to 2 April 2017, all nonduplicated CR-Ab isolated in burn patients in the BICU were screened by simplex Polymerase Chain Reaction (PCR) for the class A, B, C, and D β-lactamase genes. Sequencing was performed for NDM gene only. Genetic relatedness was determined by using pulsed field gel electrophoresis (PFGE) and by multilocus sequence typing. During the study period, 34 strains of CR-Ab were isolated in burns, mainly in blood culture (n = 14) and central vascular catheter (n = 10). CR-Ab strains were susceptible to colistin but resistant to amikacin (91%), ciprofloxacin (100%), rifampicin (97%), and trimethoprim-sulfamethoxazole (100%). All strains harbored blaOXA-51-like and blaOXA-23 genes, only or associated to blaGES (n = 26; 76%), blaADC (n = 20; 59%), blaPER-1 (n = 6; 18%) or/and blaNDM-1 (n = 3; 9%). PFGE identified 16 different clusters and revealed that most strains belonged to one major cluster A (n = 15; 44.1%). Among NDM-1 isolates, two were clonally related in PFGE and belonged to two single locus variant sequence type ST-6 and ST-85.

Conclusions

This is the first description of clonally related NDM-1 and OXA-23-producing A. baumannii strains in the largest Tunisian BICU associated with two single locus variant sequence types ST6 and ST85.
Estimation of racial and language disparities in pediatric emergency department triage using statistical modeling and natural language processing
Authors: Lee Seung-Yup (Joshua) , Alzeen Mohammed , Ahmed Abdulaziz
Published: February 2024

Objectives

The study aims to assess racial and language disparities in pediatric emergency department (ED) triage using analytical techniques and provide insights into the extent and nature of the disparities in the ED setting.

Materials and Methods

The study analyzed a cross-sectional dataset encompassing ED visits from January 2019 to April 2021. The study utilized analytical techniques, including K-mean clustering (KNN), multivariate adaptive regression splines (MARS), and natural language processing (NLP) embedding. NLP embedding and KNN were employed to handle the chief complaints and categorize them into clusters, while the MARS was used to identify significant interactions among the clinical features. The study also explored important variables, including age-adjusted vital signs. Multiple logistic regression models with varying specifications were developed to assess the robustness of analysis results.

Results

The study consistently found that non-White children, especially African American (AA) and Hispanic, were often under-triaged, with AA children having >2 times higher odds of receiving lower acuity scores compared to White children. While the results are generally consistent, incorporating relevant variables modified the results for specific patient groups (eg, Asians).

Discussion

By employing a comprehensive analysis methodology, the study checked the robustness of the analysis results on racial and language disparities in pediatric ED triage. The study also recognized the significance of analytical techniques in assessing pediatric health conditions and analyzing disparities.

Conclusion

The study’s findings highlight the significant need for equal and fair assessment and treatment in the pediatric ED, regardless of their patients’ race and language.
Estimating a directed tree for extremes
Authors: Tran Ngoc Mai , Buck Johannes , Klüppelberg Claudia
Published: February 2024

We propose a new method to estimate a root-directed spanning tree from extreme data. Prominent example is a river network, to be discovered from extreme flow measured at a set of stations. Our new algorithm utilizes qualitative aspects of a max-linear Bayesian network, which has been designed for modelling causality in extremes. The algorithm estimates bivariate scores and returns a root-directed spanning tree. It performs extremely well on benchmark data and on new data. We prove that the new estimator is consistent under a max-linear Bayesian network model with noise. We also assess its strengths and limitations in a small simulation study.
Biogeographic Perspectives on Human Genetic Diversification
Authors: Hünemeier Tábita
Published: February 2024

Modern humans originated in Africa 300,000 yr ago, and before leaving their continent of origin, they underwent a process of intense diversification involving complex demographic dynamics. Upon exiting Africa, different populations emerged on the four other inhabited continents, shaped by the interplay of various evolutionary processes, such as migrations, founder effects, and natural selection. Within each region, continental populations, in turn, diversified and evolved almost independently for millennia. As a backdrop to this diversification, introgressions from archaic species contributed to establishing different patterns of genetic diversity in different geographic regions, reshaping our understanding of our species’ variability. With the increasing availability of genomic data, it has become possible to delineate the subcontinental human population structure precisely. However, the bias toward the genomic research focused on populations from the global North has limited our understanding of the real diversity of our species and the processes and events that guided different human groups throughout their evolutionary history. This perspective is part of a series of articles celebrating 40 yr since our journal, Molecular Biology and Evolution, was founded (Russo et al. 2024). The perspective is accompanied by virtual issues, a selection of papers on human diversification published by Genome Biology and Evolution and Molecular Biology and Evolution.
CRISPR-COPIES: an in silico platform for discovery of neutral integration sites for CRISPR/Cas-facilitated gene integration
Authors: Boob Aashutosh Girish , Zhu Zhixin , Intasian Pattarawan , Jain Manan , Petrov Vassily Andrew , Lane Stephan Thomas , Tan Shih-I , Xun Guanhua , Zhao Huimin
Published: February 2024

The CRISPR/Cas system has emerged as a powerful tool for genome editing in metabolic engineering and human gene therapy. However, locating the optimal site on the chromosome to integrate heterologous genes using the CRISPR/Cas system remains an open question. Selecting a suitable site for gene integration involves considering multiple complex criteria, including factors related to CRISPR/Cas-mediated integration, genetic stability, and gene expression. Consequently, identifying such sites on specific or different chromosomal locations typically requires extensive characterization efforts. To address these challenges, we have developed CRISPR-COPIES, a COmputational Pipeline for the Identification of CRISPR/Cas-facilitated intEgration Sites. This tool leverages ScaNN, a state-of-the-art model on the embedding-based nearest neighbor search for fast and accurate off-target search, and can identify genome-wide intergenic sites for most bacterial and fungal genomes within minutes. As a proof of concept, we utilized CRISPR-COPIES to characterize neutral integration sites in three diverse species: Saccharomyces cerevisiae, Cupriavidus necator, and HEK293T cells. In addition, we developed a user-friendly web interface for CRISPR-COPIES (https://biofoundry.web.illinois.edu/copies/). We anticipate that CRISPR-COPIES will serve as a valuable tool for targeted DNA integration and aid in the characterization of synthetic biology toolkits, enable rapid strain construction to produce valuable biochemicals, and support human gene and cell therapy applications.
Human CST complex restricts excessive PrimPol repriming upon UV induced replication stress by suppressing p21
Authors: Sang Pau Biak , Jaiswal Rishi K , Lyu Xinxing , Chai Weihang
Published: February 2024

DNA replication stress, caused by various endogenous and exogenous agents, halt or stall DNA replication progression. Cells have developed diverse mechanisms to tolerate and overcome replication stress, enabling them to continue replication. One effective strategy to overcome stalled replication involves skipping the DNA lesion using a specialized polymerase known as PrimPol, which reinitiates DNA synthesis downstream of the damage. However, the mechanism regulating PrimPol repriming is largely unclear. In this study, we observe that knockdown of STN1 or CTC1, components of the CTC1/STN1/TEN1 complex, leads to enhanced replication progression following UV exposure. We find that such increased replication is dependent on PrimPol, and PrimPol recruitment to stalled forks increases upon CST depletion. Moreover, we find that p21 is upregulated in STN1-depleted cells in a p53-independent manner, and p21 depletion restores normal replication rates caused by STN1 deficiency. We identify that p21 interacts with PrimPol, and STN1 depletion stimulates p21-PrimPol interaction and facilitates PrimPol recruitment to stalled forks. Our findings reveal a previously undescribed interplay between CST, PrimPol and p21 in promoting repriming in response to stalled replication, and shed light on the regulation of PrimPol repriming at stalled forks.