bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncanonical-NF-κB activation and DDX3 inhibition reduces the HIV-1 reservoir by elimination of latently infected cells
ex-vivo
Authors: Jansen Jade , Kroeze Stefanie , Man Shirley , Andreini Matteo , Bakker Jan-Willem , Zamperini Claudio , Tarditi Alessia , Kootstra Neeltje A. , Geijtenbeek Teunis B. H. 
Published: December 2023

ABSTRACT

Latency reversal and subsequent elimination of the human immunodeficiency virus-1 (HIV-1) reservoir using a combination of compounds with different mechanisms of action are considered a promising tool for HIV-1 cure. Here, we analyzed HIV-1 reservoir reduction by targeting the two host factors; inhibitor of apoptosis proteins (IAPs) and DEAD-box polypeptide 3 (DDX3) using a SMAC mimetic (SMACm) and DDX3 inhibitor (DDX3i), respectively. We observed that SMACm efficiently reactivated HIV-1 in a latency Jurkat model, which was further enhanced by DDX3 inhibition. Strikingly, this compound combination strongly decreased the proportion of latently as well as transcriptionally active infected cells in a T cell line model with a dual-reporter virus. To determine the efficacy of compounds to eradicate the HIV-1 reservoir in people living with HIV (PWH), a novel
ex vivo
HIV-1 reservoir reduction assay (HIVRRA) was developed. DDX3i and SMACm alone reduced the HIV-1 reservoir in peripheral blood mononuclear cells (PBMCs) from the majority of PWH, whereas notably, the SMACm/DDX3i combination reduced the HIV-1 reservoir even further with 53%–90% in all PWH analyzed, while uninfected bystander cells were not affected. Our data highlight that IAPs as well as factors involved in HIV-1 replication like DDX3 are excellent targets for HIV-1 cure strategies. We show for the first time that the combination of SMACm and DDX3i reverses viral latency and specifically eliminates the HIV-1-infected cells
in vitro
and
ex vivo
.

IMPORTANCE

HIV-1 continues to be a major global health challenge. Current HIV-1 treatments are effective but need lifelong adherence. An HIV-1 cure should eliminate the latent viral reservoir that persists in people living with HIV-1. Different methods have been investigated that focus on reactivation and subsequent elimination of the HIV-1 reservoir, and it is becoming clear that a combination of compounds with different mechanisms of actions might be more effective. Here, we target two host factors, inhibitor of apoptosis proteins that control apoptosis and the DEAD-box helicase DDX3, facilitating HIV mRNA transport/translation. We show that targeting of these host factors with SMAC mimetics and DDX3 inhibitors induce reversal of viral latency and eliminate HIV-1-infected cells
in vitro
and
ex vivo
.
Validation of the PyloPlus Urea Breath Test System in pediatric patients
Authors: Price Travis K. , Realegeno Susan , Azad Kamran , Shier Kileen L. 
Published: December 2023

ABSTRACT

This study evaluated the performance of the PyloPlus Urea Breath Test (UBT) System, a Food and Drug Administration (FDA)-approved assay for diagnosis of
Helicobacter pylori
infection in adult patients, using samples from 111 pediatric patients (3–17 years old). Both qualitative results (100% correlation) and quantitative delta over baseline values (
R
2
= 0.9989) from the PyloPlus UBT strongly correlated with the Meridian BreathTek POCone UBT reference method, which is FDA approved for use in pediatric patients (3–17 years old). The PyloPlus UBT performed comparably to the BreathTek UBT without any calculation correction factors for pediatric samples. Consistent with previous studies, male pediatric patients had a significantly higher positivity rate (64%) than female pediatric patients (33%) (
P
= 0.001). There was no difference in positivity rate between two performing locations. This study shows that the PyloPlus UBT system can be used for testing pediatric patient specimens.

IMPORTANCE

For the diagnosis and post-treatment monitoring of
H. pylori
infection, non-invasive testing methodologies improve patient comfort, particularly for children. Previously, only the BreathTek UBT had FDA approval for use in pediatric patients and required an adjustment calculation based on age, height, and weight of the patient. The purpose of this study was to evaluate the performance of the PyloPlus UBT assay in a pediatric population.
Diverse nature of ClpX degradation motifs in
Streptococcus mutans
Authors: Gurung Vivek , Biswas Saswati , Biswas Indranil 
Published: December 2023

ABSTRACT

Protein homeostasis is an essential process that depends on concerted effort of different proteins involved in proper protein folding, deciding the fate of misfolded proteins by either refolding them into their proper conformation or degrading the misfolded proteins. In Gram-positive bacteria, AAA+ ATPases such as ClpX, ClpC, and ClpE interact with the proteolytic ClpP and degrade misfolded proteins. Clp ATPases also maintain amounts of different proteins based on the cellular need. In streptococci, these Clp ATPases play a crucial role in various physiological processes that contribute to virulence, cell growth and division, stress tolerance, competence development, and biofilm formation. Among the Clp ATPase complexes present in low G + C Gram-positive bacteria, ClpX/P is the major proteolytic system. In contrast to numerous ClpX/P substrates identified in
Escherichia coli
and other bacteria, very little is known about the identity of the ClpX/P substrates in streptococci. Using a proteomic approach under late logarithmic growth condition, we screened for putative substrates that might be degraded by ClpX/P; several potential substrates were identified and verified by other methods. SpxA2 is one such candidate protein, and by Western blot, we confirmed that it indeed recognizes SpxA2. We further identified Ala-Ala-Leu, located at the C-terminal of SpxA2, as a ClpX/P degradation signal. Using a green fluorescent protein reporter system, we further confirmed several ClpX/P degradation signals. Furthermore, we found that the zinc-binding domain of ClpX is needed for substrate recognition. Our
in vitro
data indicate that the adaptor or other accessory factors might be needed for the ClpX/P-mediated substrate recognition or degradation. Additional investigations are needed to determine the identity of these factors in the cell.

IMPORTANCE

Cytoplasmic Clp-related proteases play a major role in maintaining cellular proteome in bacteria. ClpX/P is one such proteolytic complex that is important for conserving protein homeostasis. In this study, we investigated the role of ClpX/P in
Streptococcus mutans
, an important oral pathogen. We identified several putative substrates whose cellular levels are regulated by ClpX/P in
S. mutans
and subsequently discovered several recognition motifs that are critical for degradation. Our study is the first comprehensive analysis of determining ClpX/P motifs in streptococci. We believe that identifying the substrates that are regulated by ClpX/P will enhance our understanding about virulence regulation in this important group of pathogens.
Justicia americana exhibits stem density–aboveground biomass relationships and variability in elemental composition and isotopic signature across tissue types and land use gradients
Authors: Wood James L. , Huff Emily 
Published: December 2023

Riverine macrophytes are increasingly understood to influence both the physical and chemical dynamics of rivers by creating biogeochemical hotspots and stabilizing benthic sediments. They contribute carbon and nutrients to both aquatic and adjacent terrestrial ecosystems through senescence and herbivory. Here, we report the relationships between Justicia americana biomass, stem length, and stem density, and % carbon (%C), % nitrogen (%N), C:N, δ15N, and δ13C relationships between tissues types (roots, stems, and leaves). Additionally, we report the effects of land use on the plant's tissue. We found that (1) J. americana stem density and dry biomass were positively correlated ( P < 0.001); (2) δ13C and %N were significantly different in leaf and root tissue; (3) δ13C and δ15N were both positively correlated across tissue types; (4) Leaf C:N was less than ½ of root and stem tissue; (5) %C in leaf tissue was positively correlated ( P < 0.05) with forest cover and negatively correlated with urbanization and watershed area; and (6) provide evidence that J. americana utilizes a C3 photosynthetic pathway. Overall, this study provides novel insight into the ecology of J. americana by elucidating the nutritional quality of different plant tissues and stoichiometric changes in the plant in response to land use.
Commonsense Knowledge-Driven Joint Reasoning Approach for Object Retrieval in Virtual Reality
Authors: Jiang Haiyan , Weng Dongdong , Dongye Xiaonuo , Luo Le , Zhang Zhenliang 
Published: December 2023

National Key Laboratory of General Artificial Intelligence, Beijing Institute for General Artificial Intelligence (BIGAI), China
Retrieving out-of-reach objects is a crucial task in virtual reality (VR). One of the most commonly used approaches for this task is the gesture-based approach, which allows for bare-hand, eyes-free, and direct retrieval. However, previous work has primarily focused on assigned gesture design, neglecting the context. This can make it challenging to accurately retrieve an object from a large number of objects due to the one-to-one mapping metaphor, limitations of finger poses, and memory burdens. There is a general consensus that objects and contexts are related, which suggests that the object expected to be retrieved is related to the context, including the scene and the objects with which users interact. As such, we propose a commonsense knowledge-driven joint reasoning approach for object retrieval, where human grasping gestures and context are modeled using an And-Or graph (AOG). This approach enables users to accurately retrieve objects from a large number of candidate objects by using natural grasping gestures based on their experience of grasping physical objects. Experimental results demonstrate that our proposed approach improves retrieval accuracy. We also propose an object retrieval system based on the proposed approach. Two user studies show that our system enables efficient object retrieval in virtual environments (VEs).
Constrained Delaunay Tetrahedrization: A Robust and Practical Approach
Authors: Diazzi Lorenzo , Panozzo Daniele , Vaxman Amir , Attene Marco 
Published: December 2023

We present a numerically robust algorithm for computing the constrained Delaunay tetrahedrization (CDT) of a piecewise-linear complex, which has a 100% success rate on the 4408 valid models in the Thingi10k dataset.
We build on the underlying theory of the well-known tetgen software, but use a floating-point implementation based on indirect geometric predicates to implicitly represent Steiner points: this new approach dramatically simplifies the implementation, removing the need for ad-hoc tolerances in geometric operations. Our approach leads to a robust and parameter-free implementation, with an empirically manageable number of added Steiner points. Furthermore, our algorithm addresses a major gap in tetgen's theory which may lead to algorithmic failure on valid models, even when assuming perfect precision in the calculations.
Our output tetrahedrization conforms with the input geometry without approximations. We can further round our output to floating-point coordinates for downstream applications, which almost always results in valid floating-point meshes unless the input triangulation is very close to being degenerate.
Design, Calibration, and Evaluation of Real-time Waveform Matching on an FPGA-based Digitizer at 10 GS/s
Authors: Trautmann Jens , Krüger Paul , Becher Andreas , Wildermann Stefan , Teich Jürgen 
Published: December 2023

Digitizing side-channel signals at high sampling rates produces huge amounts of data, while side-channel analysis techniques only need those specific trace segments containing Cryptographic Operations (COs). For detecting these segments, waveform-matching techniques have been established comparing the signal with a template of the CO’s characteristic pattern. Real-time waveform matching requires highly parallel implementations as achieved by hardware design but also reconfigurability as provided by Field-Programmable Gate Arrays (FPGAs) to adapt the matching hardware to a specific CO pattern. However, currently proposed designs process the samples from analog-to-digital converters sequentially and can only process low sampling rates due to the limited clock speed of FPGAs.
In this article, we present a parallel waveform-matching architecture capable of performing high-speed waveform matching on a high-end FPGA-based digitizer. We also present a workflow for calibrating the waveform-matching system to the specific pattern of the CO in the presence of hardware restrictions provided by the FPGA hardware. Our implementation enables waveform matching at 10 GS/s, offering a speedup of 50× compared to the fastest state-of-the-art implementation known to us. We demonstrate how to apply the technique for attacking the widespread XTS-AES algorithm using waveform matching to recover the encrypted tweak even in the presence of so-called systemic noise.
Investigation on Pomegranate (Punica granatum) Skin as a Potentially Effective Natural Food Preservative
Authors: Hossain Mohammad Lokman , Uddin Md. Nazim , Orchy Tania Nowreen , Naher Shamsun , Begum Mohajira , Haque Md. Zahurul 
Published: December 2023

The study is aimed at estimating the possibility of using pomegranate peel extracts as a natural food preservative which was investigated in fish samples. All the extracts (cold water, hot water, and 70% methanol) have been tested against five bacteria (Escherichia coli, Staphylococcus aureus, Salmonella Typhi, Bacillus megaterium, and Bacillus subtilis) using the agar disc diffusion method. Hot water extract showed the best result against B. megaterium. The zone of inhibition (ZOI) for hot water extract as crude was taken 20 μl/disc was 25 mm. Total antioxidant activity and total phenolic content (TPC) were determined for different extracts. The results of a test for TPC showed that 70% methanolic extract (MeOH) and cold water extract, respectively, comprised 263.59 mg gallic acid equivalent (GAE)/g and 197.99 mg GAE/g of total phenolics. In addition, MeOH had a total antioxidant activity of

67.55
±
5.58

mg ascorbic acid equivalent (AAE)/g while hot water extract had a total antioxidant activity of

66.86
±
3.55

mg AAE/g. The extracts were applied to Ompok pabda fish, and the fish were preserved in prepared extracts for 24 hours in the open air. Total volatile nitrogen (TVN) and sensory parameters were evaluated at regular intervals of 0, 4, 12, 18, and 24 hours. The TVN value of the prepared extracts was found in order of hot water> MeOH> cold water. Fish preserved in hot water extract was in the acceptable range even after 24 hours. Methanol extract and hot water yielded superior outcomes in preserving the fish.
Association of Neighborhood-Level Marginalization With Health Care Use and Clinical Outcomes Following Hospital Discharge in Patients Who Underwent Coronary Catheterization for Acute Myocardial Infarction in a Single-Payer Health Care System
Authors: Akioyamen Leo E. , Abdel-Qadir Husam , Han Lu , Sud Maneesh , Mistry Nikhil , Alter David A. , Atzema Clare L. , Austin Peter C. , Bhatia R. Sacha , Booth Gillian L. , Dhalla Irfan , Ha Andrew C.T. , Jackevicius Cynthia A. , Kapral Moira K. , Krumholz Harlan M. , Lee Douglas S. , McNaughton Candace D. , Roifman Idan , Schull Michael J. , Sivaswamy Atul , Tu Karen , Udell Jacob A. , Wijeysundera Harindra C. , Ko Dennis T. 
Published: December 2023

BACKGROUND:
Canadian data suggest that patients of lower socioeconomic status with acute myocardial infarction receive less beneficial therapy and have worse clinical outcomes, raising questions regarding care disparities even in universal health care systems. We assessed the contemporary association of marginalization with clinical outcomes and health services use.

METHODS:
Using clinical and administrative databases in Ontario, Canada, we conducted a population-based study of patients aged ≥65 years hospitalized for their first acute myocardial infarction between April 1, 2010 and March 1, 2019. Patients receiving cardiac catheterization and surviving 7 days postdischarge were included. Our primary exposure was neighborhood-level marginalization, a multidimensional socioeconomic status metric. Neighborhoods were categorized by quintile from Q1 (least marginalized) to Q5 (most marginalized). Our primary outcome was all-cause mortality. A proportional hazards regression model with a robust variance estimator was used to quantify the association of marginalization with outcomes, adjusting for risk factors, comorbidities, disease severity, and regional cardiologist supply.

RESULTS:
Among 53 841 patients (median age, 75 years; 39.1% female) from 20 640 neighborhoods, crude 1- and 3-year mortality rates were 7.7% and 17.2%, respectively. Patients in Q5 had no significant difference in 1-year mortality (hazard ratio [HR], 1.08 [95% CI, 0.95–1.22]), but greater mortality over 3 years (HR, 1.13 [95% CI, 1.03–1.22]) compared with Q1. Over 1 year, we observed differences between Q1 and Q5 in visits to primary care physicians (Q1, 96.7%; Q5, 93.7%) and cardiologists (Q1, 82.6%; Q5, 72.6%), as well as diagnostic testing. There were no differences in secondary prevention medications dispensed or medication adherence at 1 year.

CONCLUSIONS:
In older patients with acute myocardial infarction who survived to hospital discharge, those residing in the most marginalized neighborhoods had a greater long-term risk of mortality, less specialist care, and fewer diagnostic tests. Yet, there were no differences across socioeconomic status in prescription medication use and adherence.
Robust frequency-dependent diffusional kurtosis computation using an efficient direction scheme, axisymmetric modelling, and spatial regularization
Authors: Hamilton Jake , Xu Kathy , Geremia Nicole , Prado Vania F. , Prado Marco A.M. , Brown Arthur , Baron Corey A. 
Published: December 2023

Abstract
Frequency-dependent diffusion MRI (dMRI) using oscillating gradient encoding and diffusional kurtosis imaging (DKI) techniques have been shown to provide additional insight into tissue microstructure compared to conventional dMRI. However, a technical challenge when combining these techniques is that the generation of the large b-values (≥2000 s/mm2) required for DKI is difficult when using oscillating gradient diffusion encoding. While efficient encoding schemes can enable larger b-values by maximizing multiple gradient channels simultaneously, they do not have sufficient directions to enable the estimation of directional kurtosis parameters. Accordingly, we investigate a DKI fitting algorithm that combines axisymmetric DKI fitting, a prior that enforces the same axis of symmetry for all oscillating gradient frequencies, and spatial regularization, which together enable robust DKI fitting for a 10-direction scheme that offers double the b-value compared to traditional encoding schemes. Using data from mice (oscillating frequencies of 0, 60, and 120 Hz) and humans (0 Hz only), we first show that axisymmetric DKI fitting provides comparable or even slightly improved image quality as compared to kurtosis tensor fitting, and improved DKI map quality when using an efficient encoding scheme with averaging as compared to a traditional scheme with more encoding directions. We also demonstrate that enforcing consistent axes of symmetries across frequencies improves fitting quality, and spatial regularization during fitting preserves spatial features better than using Gaussian filtering prior to fitting, which is an oft-reported pre-processing step for DKI. Thus, the use of an efficient 10-direction scheme combined with the proposed DKI fitting algorithm provides robust maps of frequency-dependent directional kurtosis which may offer increased sensitivity to cytoarchitectural changes that occur at various cellular spatial scales over the course of healthy aging, and due to pathological alterations.
The Limiting Dynamics of SGD: Modified Loss, Phase-Space Oscillations, and Anomalous Diffusion
Authors: Kunin Daniel , Sagastuy-Brena Javier , Gillespie Lauren , Margalit Eshed , Tanaka Hidenori , Ganguli Surya , Yamins Daniel L. K. 
Published: December 2023

Abstract
In this work, we explore the limiting dynamics of deep neural networks trained with stochastic gradient descent (SGD). As observed previously, long after performance has converged, networks continue to move through parameter space by a process of anomalous diffusion in which distance traveled grows as a power law in the number of gradient updates with a nontrivial exponent. We reveal an intricate interaction among the hyperparameters of optimization, the structure in the gradient noise, and the Hessian matrix at the end of training that explains this anomalous diffusion. To build this understanding, we first derive a continuous-time model for SGD with finite learning rates and batch sizes as an underdamped Langevin equation. We study this equation in the setting of linear regression, where we can derive exact, analytic expressions for the phase-space dynamics of the parameters and their instantaneous velocities from initialization to stationarity. Using the Fokker-Planck equation, we show that the key ingredient driving these dynamics is not the original training loss but rather the combination of a modified loss, which implicitly regularizes the velocity, and probability currents that cause oscillations in phase space. We identify qualitative and quantitative predictions of this theory in the dynamics of a ResNet-18 model trained on ImageNet. Through the lens of statistical physics, we uncover a mechanistic origin for the anomalous limiting dynamics of deep neural networks trained with SGD. Understanding the limiting dynamics of SGD, and its dependence on various important hyperparameters like batch size, learning rate, and momentum, can serve as a basis for future work that can turn these insights into algorithmic gains.
Goliath’s Humanimal Body: Masculinity, Ethnicity, and Animal Imagery in 1 Samuel 17
Authors: Millar Suzanna 
Published: December 2023

Abstract
In 1 Samuel 17, Goliath is described using animal imagery, depicted like a sea creature, a lion and bear, a dog, and scavengers’ prey. I argue that these images present Goliath as not fully human, and contribute to the construction of his masculinity and ethnicity. This article traces the following trajectory: masculinity is established then undermined; the foreigner encroaches then is expelled. Goliath is introduced as a hypermasculine ultrapredator. Akin to a sea monster from the chaotic beyond, he has an exoskeleton of fish-scale armour (17:5). David then likens Goliath to lions and bears (17:34–37), imperial symbols for fearsome foreign nations. David, though, can grasp their beards (overturning their masculinity) and slay them. Goliath perceives David to be treating him like a scavenging dog (17:43)—a dishonorable creature encroaching where it does not belong. Consequently, the opponents threaten to give the other’s flesh to the birds and beasts (17:44, 46). Their bodies’ masculine wholeness is disarticulated by scavengers and expelled from society.