bluuebunny/crossref_metadata_2025 huggingface dataset:
Allelic variants confer Arabidopsis adaptation to small regional environmental differences
Authors: Wijfjes Raúl Y. , Boesten René , Becker Frank F. M. , Theeuwen Tom P. J. M. , Snoek Basten L. , Mastoraki Maria , Verheijen Jelle J. , Güvencli Nuri , Denkers Lissy‐Anne M. , Koornneef Maarten , van Eeuwijk Fred A. , Smit Sandra , de Ridder Dick , Aarts Mark G. M.
Published: October 2024

Natural populations of Arabidopsis thaliana provide powerful systems to study the adaptation of wild plant species. Previous research has predominantly focused on global populations or accessions collected from regions with diverse climates. However, little is known about the genetics underlying adaptation in regions with mild environmental clines. We have examined a diversity panel consisting of 192 A. thaliana accessions collected from the Netherlands, a region with limited climatic variation. Despite the relatively uniform climate, we identified evidence of local adaptation within this population. Notably, semidwarf accessions, due to mutation of the GIBBERELLIC ACID REQUIRING 5 (GA5) gene, occur at a relatively high frequency near the coast and these displayed enhanced tolerance to high wind velocities. Additionally, we evaluated the performance of the population under iron deficiency conditions and found that allelic variation in the FE SUPEROXIDE DISMUTASE 3 (FSD3) gene affects tolerance to low iron levels. Moreover, we explored patterns of local adaptation to environmental clines in temperature and precipitation, observing that allelic variation at LA RELATED PROTEIN 1C (LARP1c) likely affects drought tolerance. Not only is the genetic variation observed in a diversity panel of A. thaliana collected in a region with mild environmental clines comparable to that in collections sampled over larger geographic ranges but it is also sufficiently rich to elucidate the genetic and environmental factors underlying natural plant adaptation.
A gene cluster for polyamine transport and modification improves salt tolerance in tomato
Authors: Yang Jie , Zhang Zhonghui , Li Xianggui , Guo Langchen , Li Chun , Lai Jun , Han Yige , Ye Weizhen , Miao Yuanyuan , Deng Meng , Cao Peng , Zhang Yueran , Ding Xiangyu , Zhang Jianing , Yang Jun , Wang Shouchuang
Published: October 2024

Polyamines act as protective compounds directly protecting plants from stress‐related damage, while also acting as signaling molecules to participate in serious abiotic stresses. However, the molecular mechanisms underlying these effects are poorly understood. Here, we utilized metabolome genome‐wide association study to investigate the polyamine content of wild and cultivated tomato accessions, and we discovered a new gene cluster that drove polyamine content during tomato domestication. The gene cluster contains two polyphenol oxidases (SlPPOE and SlPPOF), two BAHD acyltransferases (SlAT4 and SlAT5), a coumaroyl‐CoA ligase (Sl4CL6), and a polyamine uptake transporter (SlPUT3). SlPUT3 mediates polyamine uptake and transport, while the five other genes are involved in polyamine modification. Further salt tolerance assays demonstrated that SlPPOE, SlPPOF, and SlAT5 overexpression lines showed greater phenolamide accumulation and salt tolerance as compared with wild‐type (WT). Meanwhile, the exogenous application of Spm to SlPUT3‐OE lines displayed salt tolerance compared with WT, while having the opposite effect in slput3 lines, confirms that the polyamine and phenolamide can play a protective role by alleviating cell damage. SlPUT3 interacted with SlPIP2;4, a H2O2 transport protein, to maintain H2O2 homeostasis. Polyamine‐derived H2O2 linked Spm to stress responses, suggesting that Spm signaling activates stress response pathways. Collectively, our finding reveals that the H2O2‐polyamine‐phenolamide module coordinately enhanced tomato salt stress tolerance and provide a foundation for tomato stress‐resistance breeding.
Tubings, chord diagrams, and Dyson–Schwinger equations
Authors: Balduf Paul‐Hermann , Cantwell Amelia , Ebrahimi‐Fard Kurusch , Nabergall Lukas , Olson‐Harris Nicholas , Yeats Karen
Published: October 2024

We give series solutions to single insertion place propagator‐type systems of Dyson–Schwinger equations using binary tubings of rooted trees. These solutions are combinatorially transparent in the sense that each tubing has a straightforward contribution. The Dyson–Schwinger equations solved here are more general than those previously solved by chord diagram techniques, including systems and noninteger values of the insertion parameter . We remark on interesting combinatorial connections and properties.
Children’s involvement in the development and evaluation of parent-focused mental health interventions: a scoping review protocol
Authors: Nowland Rebecca , Christian Danielle L. , Aspinall Georgia , Berzins Kathryn , Khalid Sundus , Ahuja Shalini , Gallagher Lucy , Gee Brioney , Mickleburgh Ella , Fernandes Blossom , Kelsall Afra , Randell Becca , Michelson Daniel
Published: October 2024

Objective:

This review will i) describe methods used to involve children in the development and/or evaluation of parent-focused interventions to prevent or treat child mental health problems; ii) summarize the perspectives of children or adults about these methods; iii) highlight any reported enablers and barriers; and iv) identify guidance and make recommendations for further research.

Introduction:

Parent-focused interventions (where children are not primarily involved or are excluded) have been implemented to address various child mental health outcomes. However, it is unclear to what extent, and to what end, children have been involved in developing and evaluating such interventions. Engaging children in formative research activities, with or without their parents, has the potential to improve quality and implementation of the interventions.

Inclusion criteria:

Eligible studies will involve children (5–12 years) in the development and/or evaluation of parent-focused interventions aimed at preventing or treating common child mental health problems (eg, anxiety, depression, ADHD, disruptive behavior) delivered in any setting (eg, school, community, home, health facility). Eligible interventions may include one or more psychosocial practice elements targeting behavioral, cognitive, emotional, interpersonal, social, and/or environmental factors implicated in the onset and maintenance of child mental health problems.

Methods:

Comprehensive searches will be conducted in 5 electronic databases (PsycINFO, MEDLINE, CINAHL, Embase, and Scopus). Gray literature will be sourced using Google as well as through searches of key organization websites and via notifications on social media. Only English-language primary studies will be considered. Findings across a range of methodologies will be charted and combined into a narrative synthesis.

Review registration:

Open Science Framework https://osf.io/x9376/
Predicting Leidenfrost Temperature and Effects of Impact Conditions on Droplet Size Distribution in Film-Boiling Regime
Authors: Patwary Mohammad F. F. , Isik Doruk , Kong Song-Charng , Mayhew Eric , Kim Kenneth S. , Kweon Chol-Bum M.
Published: October 2024

The interaction of a droplet with a solid wall is relevant in various engineering applications. The properties of the resulting secondary droplets are determined by the wall temperature, ambient pressure, impact momentum, and impact angle. This paper presents a comprehensive characterization of drop–wall interactions and the subsequent atomization as a function of the combined effects of such parameters. A drop–wall interaction model is derived for F-24 liquid fuel droplets using smoothed particle hydrodynamics (SPH). F-24 is a derivative of Jet-A aviation fuel with military additives, and it is the focus of this study due to its common use in military applications. The model can predict different impact outcome regimes (deposition, rebound, contact-splash, and film-splash) for different ambient pressures, wall temperatures, and impact parameters. The model also addresses the effect of ambient pressure on the Leidenfrost behavior. Size distributions of secondary droplets are compared for vertical and nonvertical impacts of F-24 droplets on superheated surfaces in the film-boiling regime. The nondimensional Sauter mean diameter (SMD) of the secondary droplets varies based on the position in the impact plane for all the nonvertical impacts but remains almost unchanged for vertical impacts. The zone of leading direction for nonvertical impact consists of larger secondary droplets, and the size decreases toward the zone of trailing direction. An empirical relation is proposed to represent this trend. This research sheds light on successive droplet impacts by studying the effects of impact frequency on SMD evolution. The results are compared to single droplet impact cases for different fuels and Weber numbers. The size of secondary droplets for successive impacts is observed to be nearly indistinguishable from that of single droplet vertical impacts.
The Bressesque Surface: Distribution of Screw Pitch
Authors: Dooner David , Garcia-Garcia Ricardo , Rico José M.
Published: October 2024

Presented is an overview of the T-N interpretation of the famous planar Euler–Savary formula. The T-N spatial analog interpretation consists of two components: the established axial component along with a new transverse component. The axial component entails the spatial Euler–Savary relation involving the Disteli axis and motion parallel to the instantaneous screw axis (ISA). The transverse component emulates the classical planar Euler–Savary relation involving motion perpendicular to the ISA. Within the T-N interpretation is an inflection surface together with a family of Bressesque surfaces. Traditionally, a Bresse circle is a planar motion concept defined by points with zero tangential acceleration. Here, the Bressesque surfaces do not consider accelerations akin to the planar scenario. Instead, the Bressesque surfaces are defined as a linear combination of two axes of the inflection surface. These two axes are used to establish a skew axis gear set where the axodes are tangent along a generator of the Bressesque surface. This tangency is the ISA for the gear set. What is new is the screw pitch for each generator of the hyperboloidal Bressesque surface. Two graphs are shown: the first graph is the variation in screw pitch in terms of the ray angle and the second graph is the variation in speed ratio of the skew axes gear set in terms of the ray angle.
A Comparative Analysis Among Dynamics Modeling Approaches for Space Manipulator Systems
Authors: Tantravahi Santosh
Published: October 2024

This paper presents a comparative analysis on the space manipulator systems dynamics modeling approaches, namely, the standard approach (SA) and the dual quaternion based dynamics modeling approach. A detailed analysis supported by the results from numerical simulations, comparing the two approaches in terms of operational count and execution time, has been presented to determine which approach is computationally and temporally efficient.
Epsilon-Greedy Thompson Sampling to Bayesian Optimization
Authors: Do Bach , Adebiyi Taiwo , Zhang Ruda
Published: October 2024

Bayesian optimization (BO) has become a powerful tool for solving simulation-based engineering optimization problems thanks to its ability to integrate physical and mathematical understandings, consider uncertainty, and address the exploitation–exploration dilemma. Thompson sampling (TS) is a preferred solution for BO to handle the exploitation–exploration tradeoff. While it prioritizes exploration by generating and minimizing random sample paths from probabilistic models—a fundamental ingredient of BO–TS weakly manages exploitation by gathering information about the true objective function after it obtains new observations. In this work, we improve the exploitation of TS by incorporating the ε-greedy policy, a well-established selection strategy in reinforcement learning. We first delineate two extremes of TS, namely the generic TS and the sample-average TS. The former promotes exploration, while the latter favors exploitation. We then adopt the ε-greedy policy to randomly switch between these two extremes. Small and large values of ε govern exploitation and exploration, respectively. By minimizing two benchmark functions and solving an inverse problem of a steel cantilever beam, we empirically show that ε-greedy TS equipped with an appropriate ε is more robust than its two extremes, matching or outperforming the better of the generic TS and the sample-average TS.
Machine Learning in Wear Prediction
Authors: Shah Raj , Pai Nikhil , Thomas Gavin , Jha Swarn , Mittal Vikram , Shirvni Khosro , Liang Hong
Published: October 2024

As modern devices and systems continue to advance, device wear remains a key factor in limiting their performance and lifetime, as well as environmental and health effects. Traditional approaches often rely on wear prediction based on physical models, but due to device complexity and uncertainty, these methods often fail to provide accurate predictions and accurate wear identification. Machine learning, as a data-driven approach based on its ability to discover patterns and correlations in complex systems, has enormous potential for monitoring and predicting device wear. Here, we review recent advances in applying machine learning for predicting the wear of mechanical components. Machine learning for wear prediction shows significant potential in optimizing material selection, manufacturing processes, and equipment maintenance, ultimately enhancing productivity and resource efficiency. Successful implementation relies on careful data collection, standardized evaluation methods, and the selection of effective algorithms, with artificial neural networks (ANNs) frequently demonstrating notable success in predictive accuracy.
Dual-mode draw resonance instability regulated by concentration fluctuation in the polymer solutions casting
Authors: Nie Cui , Zhang Mengnan , Peng Fan , Zeng Jun , Cui Kunpeng , Tian Fucheng , Li Liangbin
Published: October 2024

Based on the two-fluid model, we successfully simulated the film casting process of the polymer solution system and observed the unique response wave of the film thickness and the concentration via applying perturbation. We identify that this instability pattern is essentially the product under the coupling effect of viscoelastic stress and osmotic pressure from fluctuations on different scales, which causes it to exhibit biperiodic characteristics. We call this new instability mode known as dual-mode draw resonance instability. Among them, the concentration oscillation predominates, thereby limiting the critical draw ratio Drc of the system. Through sorting out the molecular image of the polymer concentration response to perturbation, the relevant parameters are extracted, and the law of their influence on the Drc further verifies our conclusion and provides guidance for actual production.
Women Movement Behaviors During Pregnancy and 2 Years After Childbirth: Physical Activity, Sedentary Time, Sleep, and Rhythm Changes in a Brazilian Birth Cohort
Authors: Wendt Andrea , Costa Martins Rafaela , Kramer Fiala Machado Adriana , Ricardo Luiza I.C. , Ginar da Silva Shana , Gonçalves Cordeiro da Silva Bruna , Mielke Gregore I. , Rodrigues Domingues Marlos , Hallal Pedro C. , Crochemore-Silva Inácio
Published: October 2024

Objective: To describe physical activity (PA), sleep, and rhythm patterns during 24-hr cycles from the second trimester of pregnancy up to 2 years after childbirth. Methods: This longitudinal study used data from mothers of the 2015 Pelotas Birth Cohort (Brazil). Women were invited to wear the accelerometer during 7 days on the nondominant wrist during the second trimester of pregnancy and 2 years after childbirth. Data collected included PA, sleep, and rhythm variables. We compared the means/medians of variables during the pregnancy and 2 years after the childbirth. We also describe the shape of acceleration across the day in the two evaluated periods and stratified this curve according to covariables. Results: This study includes data from 1,293 women with valid accelerometer data for both periods. The nonbouted moderate-to-vigorous PA average was 94 min during pregnancy and increased to 122 min 2 years after childbirth (p < .001). Sleep decreased by 11 min (388–377 min; p < .001) in the evaluated period. The pattern of acceleration across the day did not change in the evaluated period with two marked spikes of activity at 10 a.m. and 6 p.m. The amount of activity, however, increased. Conclusions: These findings may be helpful to better understand changes in PA and sleep during this specific period of life and assist in planning recommendations.
Low penicillin susceptibility in
Streptococcus mitis/oralis
from bloodstream infections in pediatric populations
Authors: Zhou Jian-Ming , Wu Cai-Yu , Li Jian-Ping , Ye Yi-Hua , Fang Chao , Zhou Ming-Ming
Published: October 2024

Streptococcus mitis/oralis
can cause invasive diseases, including bloodstream infections. However, existing research primarily focuses on specific populations, and limited studies have been conducted on the prevalence of bloodstream infection caused by
S. mitis/oralis
across the entire pediatric population. Therefore, clinical data of
S. mitis/oralis
isolated from blood samples at Children’s Hospital, Zhejiang University School of Medicine, during the period 2019–2023 were collected retrospectively to provide a comprehensive understanding of the clinical characteristics and drug resistance patterns associated with bloodstream infections caused by
S. mitis/oralis
in pediatric populations. There were 57 (43.5%) instances of contamination across various departments, indicating a relatively dispersed pattern. Bloodstream infections caused by
S. mitis/oralis
are notably prevalent among pediatric patients with hematological diseases and tumors. The susceptibility rates of the 74
S. mitis/oralis
isolates to different antibiotics were as follows: penicillin (23%), ceftriaxone (74.3%), levofloxacin (86.5%), chloramphenicol (89.2%), erythromycin (27%), clindamycin (67.6%), linezolid (100%), and vancomycin (100%). Notably, 21.6% of the isolates exhibited multi-drug resistance (MDR). The predominant mode of MDR in
S. mitis/oralis
infections was identified as resistance to β-lactams, erythromycin, and clindamycin. The observed low susceptibility rate to penicillin, coupled with the emergence of MDR strains, underscores the imperative for continuous monitoring of the evolving antimicrobial resistance in
S. mitis/oralis
.

IMPORTANCE

Existing research primarily focuses on specific populations, such as those with hematopathy or tumors, who experience
Streptococcus mitis/oralis
bacteremia. Limited studies have been conducted on the prevalence of bloodstream infections caused by
S. mitis/oralis
across the entire pediatric population. It was found that the contamination rate of
S. mitis/oralis
isolated from blood cultures was notably high in our study. Therefore, this study evaluated the clinical characteristics and drug resistance patterns of bloodstream infections caused by
S. mitis/oralis
across the entire pediatric populations, explicitly excluding cases of blood culture contamination. The observed low susceptibility rate to penicillin, coupled with the emergence of multi-drug-resistant strains, underscores the imperative for continuous monitoring of the evolving antimicrobial resistance in
S. mitis/oralis
.
Strength of viscous subduction interfaces: A global compilation
Authors: Abila Ana Lorena , Behr Whitney M. , Ruh Jonas
Published: October 2024

The long- and short-term dynamics of subduction zones are strongly affected by interface rheology. Current estimates of interface viscosity are based on endmember flow laws or simple mixing models, but the variation of possible materials on the subduction interface theoretically permits viscosity variations of up to five orders of magnitude. To better constrain the range of strength along deep/viscous subduction interfaces, we compiled a global database of rock types and block-and-matrix distributions in exhumed deep subduction interface mélange shear zones. We applied numerical shear experiments to each shear zone to quantify their bulk shear strengths/viscosities. Our results show that natural subduction shear zones have viscosities ranging from ~1018 to 1020 Pa·s and shear strengths of ~1–100 MPa. The variation among them is dominantly controlled by temperature, but even for shear zones deformed at the same temperature, variations of up to a factor of 50 are observed. These variations are attributed to differences in matrix composition, shear zone width, and block distributions. Our results are consistent with paleopiezometric and force-balance–derived estimates of interface strength, and they confirm the importance of variation in geological inputs and their spatial distribution along the interface for subduction dynamics.
Best practice guide for patellofemoral pain based on synthesis of a systematic review, the patient voice and expert clinical reasoning
Authors: Neal Bradley Stephen , Lack Simon David , Bartholomew Clare , Morrissey Dylan
Published: October 2024

Objective

Define a best practice guide for managing people with patellofemoral pain (PFP).

Methods

A mixed-methods convergent segregated synthesis of meta-analysed data with a thematic analysis of semistructured interviews and focus groups. Agreement between subproject results informed the strength of clinical recommendation for interventions eligible for best practice recommendation.

Data sources

Medline, Web of Science, Scopus, reference lists and citation tracking; semistructured interviews of people with PFP; and semistructured interviews and focus groups with clinical experts.

Eligibility criteria

High-quality (PEDro scale >7) randomised controlled trials (RCTs) were retained for efficacy estimation using meta-analysis. People with PFP were required to have experienced an episode of care in the past 6 months and clinical experts were required to have>5 years of clinical experience alongside direct involvement in research.

Results

Data from 65 high-quality RCTs involving 3796 participants informed 11 meta-analyses of interventions. Interviews with 12 people with PFP led to 3 themes and interviews with 19 clinical experts led to 4 themes. These were further explored in three clinical expert focus groups. Best practice for PFP should first involve understanding a patient’s background risk factors, their reasons for seeking care, greatest symptoms, and physical impairments, to inform treatment selection. Synthesis led to six distinct interventions being recommended. Knee-targeted±hip-targeted exercise therapy underpinned by education should be delivered, with additional supporting interventions such as prefabricated foot orthoses, manual therapy, movement/running retraining, or taping decided on and tailored to a patient’s needs and preferences.

Conclusion

A best practice guide based on a synthesis of three data streams recommends that exercise therapy and education be delivered as the primary intervention for people with PFP. Prescription of other supporting interventions should be aligned with the individual patient’s particular presentation following a thorough assessment.
Global landscape of nicotine and tobacco products additives policies
Authors: Oliveira da Silva Andre Luiz , Bialous Stella
Published: October 2024

Introduction

Product design is a key tobacco industry strategy to recruit consumers and hinder cessation. An important technology in tobacco product design is the use of additives including those that create characterising flavours, that is, flavours that are perceived by taste and or smell by the user. To curb youth use, many countries are implementing policies to limit the use of flavours and other additives in tobacco products. This paper reviews the global landscape of tobacco additives policies including those focusing only on flavouring additives, updating a previous review.

Methods

We gathered additives policy data from available online sources of tobacco control policies including parties’ reports to the WHO Framework Convention on Tobacco Control (where WHO refers to World Health Organization), the website Tobacco Control Laws, government websites, searches with the Google search engine and consultations with the WHO to ensure comprehensiveness of the assessment. The policies were classified according to their objective and characteristics: Labelling regulations, sales bans and tobacco product design regulations. We classified and organised the regulations according to their stated intent.

Results

We found that 62 countries had tobacco products’ additives-related regulations at the regional, national or subnational levels. Most of these regulations focused on flavouring additives especially bans on the selling, importing and manufacturing tobacco products with characterising flavours.

Conclusions

The data demonstrate various global policies addressing additives and/or flavours and a range of definitions of additives and flavours. Establishing common definitions and standards could facilitate cooperation between countries and regions.
An Updated Survey of Trends in the Surgical Management of Thumb Carpometacarpal Arthritis – The Increasing Popularity of the Suture Suspension Arthroplasty
Authors: WANG William L. , NEAL William H. E. , YANG S. Steven
Published: October 2024

Background: The purpose of this study was to conduct an updated survey of American Society for Surgery of the Hand (ASSH) membership to evaluate current preferences for surgical management of thumb CMC arthritis. Past surveys have demonstrated LRTI to be the most preferred surgical technique. We hypothesised that current surgical preferences for thumb CMC arthritis have changed over the last several years due to rising popularity of high-strength suture implants.

Methods: A 22-question survey inquired about the preferences for the surgical management of basal joint arthritis and was sent to the ASSH membership. Descriptive statistics were calculated on all survey questions. Chi-squared analysis was used to compare differences in thumb CMC arthroplasty preferences across respondents.

Results: A total of 1,499 responses were available for analysis, yielding a response rate of 29.9%. For surgical management of basal joint arthritis in the primary setting, the largest percentage of respondents preferred open trapeziectomy with suture suspension arthroplasty (39.2%); amongst them, over half (56%) used a high-strength suture implant. This was followed by open trapeziectomy with LRTI (38.3%). In the revision setting, most respondents preferred open trapeziectomy with suture suspension arthroplasty (53.5%), followed by LRTI (24.6%). In determining the choice of procedure, respondents felt some form of metacarpal suspension and implant cost to be more important factors than ligament reconstruction and interposition. A higher proportion of international members (16.2%) utilised implant arthroplasty than US/Canadian members (1.1%; p < 0.01).

Conclusions: Past surveys have demonstrated LRTI to be the most preferred surgical technique. The current survey demonstrates open trapeziectomy and suture suspension arthroplasty, especially using high-strength suture implants, gaining popularity amongst surgeons, while open trapeziectomy and LRTI decreasing in preference. Suture suspension arthroplasty is now the preferred surgical technique in both the primary and revision setting.

Level of Evidence: Level IV (Therapeutic)
Ultrasonographic Evaluation of Flexor Pollicis Longus Tendon Location in Various Functional Hand Positions
Authors: RATANAKOOSAKUL Warot , ANANTAVORASAKUL Navapong , SIRIPOONYOTHAI Sopinan , KITTITHAMVONGS Piyabuth , MALUNGPAISHROPE Kanchai , UERPAIROJKIT Chairoj
Published: October 2024

Background: Flexor pollicis longus (FPL) tendon injury is a significant complication following distal radius fractures treated with volar locking plate fixation. We were unable to find any studies investigating the FPL tendon in relation to the distal radius in various functional hand positions. The aim of this study is to comprehensively evaluate FPL tendon location in essential functional hand positions commonly encountered in daily life, including pulp pinch, key pinch, chuck grip, power grip, cylindrical grasp and spherical grasp.

Methods: We assess the position of the FPL tendon and finger flexor tendons concerning the radius in various functional hand positions. Sixty-two wrists in 31 healthy volunteers were examined using transverse ultrasonography at the watershed area of the radius in six different functional hand positions, including pulp pinch, key pinch, chuck grip, power grip, cylindrical grasp and spherical grasp.

Results: The shortest distance between the FPL tendon and radius was observed in the key pinch position with a mean of 3.37 mm, while the cylindrical grasp position showed the farthest distance with a mean of 4.21 mm.

Conclusions: The location of the FPL tendon and finger flexor tendons varies across different functional hand positions. Our study shows that these tendons are closest to the radius when the hand is in the key pinch position.

Level of Evidence: Level IV (Diagnostic)
Bias Mitigation and Representation Optimization for Noise-Robust Cross-modal Retrieval
Authors: Liu Yu , Chen Haipeng , Qin Guihe , Song Jincai , Yang Xun
Published: October 2024

The remarkable progress in cross-modal retrieval relies on accurately-annotated multimedia datasets. In practice, most existing datasets used for training cross-modal retrieval models are automatically collected from the Internet to reduce data collection costs. However, it inevitably contains mismatched pairs,
i.e.
, noisy correspondences, thus degrading the model performance. Recent advances utilize the predicted similarity distribution of individual samples for noise validation and correction, which easily faces two challenging dilemmas: 1) confirmation bias and 2) unstable performance with increasing noise. In light of the above, we propose a generalized
B
ias
M
itigation and
R
epresentation
O
ptimization framework (BMRO). Specifically, we propose a
Bias Estimator
(BE) to estimate the unbiased confidence factor of a sample by contrasting it against its nearest neighbors. Unbiased confidence factor can precisely adjust sample contribution and enhance accurate sample division. This facilitates the
Adaptive Representation Optimizer
(ARO) in providing tailored optimization strategies for clean and noisy samples. ARO performs contrastive learning between clean samples and generated hard samples, thus promoting the generalizability and robustness of the representation. Besides, it utilizes complementary learning to reduce incorrect guidance from noisy samples. Extensive experiments on five visual-text benchmarks verify that our BMRO can significantly improve the matching accuracy and performance stability against noisy correspondences.
Emerging roles of ketone bodies in cardiac fibrosis
Authors: Maduray Kellina , Zhong Jingquan
Published: October 2024

Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition within the myocardium, poses a significant challenge in cardiovascular health, contributing to various cardiac pathologies. Ketone bodies (KBs), particularly β-hydroxybutyrate (β-OHB), have emerged as subjects of interest due to their potential cardioprotective effects. However, their specific influence on cardiac fibrosis remains underexplored. This literature review comprehensively examines the relationship between KBs and cardiac fibrosis, elucidating potential mechanisms through which KBs modulate fibrotic pathways. A multifaceted interplay exists between KBs and key mediators of cardiac fibrosis. While some studies indicate a profibrotic role for KBs, others highlight their potential to attenuate fibrosis and cardiac remodeling. Mechanistically, KBs may regulate fibrotic pathways through modulation of cellular components such as cardiac fibroblasts, macrophages, and lymphocytes, as well as extracellular matrix proteins. Furthermore, the impact of KBs on cellular processes implicated in fibrosis, including oxidative stress, chemokine and cytokine expression, caspase activation, and inflammasome signaling is explored. While conflicting findings exist regarding the effects of KBs on these processes, emerging evidence suggests a predominantly beneficial role in mitigating inflammation and oxidative stress associated with fibrotic remodeling. Overall, this review underscores the importance of elucidating the complex interplay between KB metabolism and cardiac fibrosis. The insights gained have the potential to inform novel therapeutic strategies for managing cardiac fibrosis and associated cardiovascular disorders, highlighting the need for further research in this area.
Homeostatic regulation of brain activity: from endogenous mechanisms to homeostatic nanomachines
Authors: Michetti Caterina , Benfenati Fabio
Published: October 2024

After the initial concepts of the constancy of the internal milieu or homeostasis, put forward by Claude Bernard and Walter Cannon, homeostasis emerged as a mechanism to control oscillations of biologically meaningful variables within narrow physiological ranges. This is a primary need in the central nervous system that is continuously subjected to a multitude of stimuli from the internal and external environments that affect its function and structure, allowing to adapt the individual to the ever-changing daily conditions. Preserving physiological levels of activity despite disturbances that could either depress neural computation or excessively stimulate neural activity is fundamental, and failure of these homeostatic mechanisms can lead to brain diseases. In this review, we cover the role and main mechanisms of homeostatic plasticity involving the regulation of excitability and synaptic strength from the single neuron to the network level. We analyze the relationships between homeostatic and Hebbian plasticity and the conditions under which the preservation of the excitatory/inhibitory balance fails, triggering epileptogenesis and eventually epilepsy. Several therapeutic strategies to cure epilepsy have been designed to strengthen homeostasis when endogenous homeostatic plasticity mechanisms have become insufficient or ineffective to contrast hyperactivity. We describe “on demand” gene therapy strategies, including optogenetics, chemogenetics, and chemo-optogenetics, and particularly focus on new closed loop sensor-actuator strategies mimicking homeostatic plasticity that can be endogenously expressed to strengthen the homeostatic defenses against brain diseases.
COMMD5 counteracts cisplatin-induced nephrotoxicity by maintaining tubular epithelial integrity and autophagy flux
Authors: Ogasawara-Nosoko Maiko , Matsuda Hiroyuki , Ikeda Jin , Abe Masanaori , Masuhiro Yoshikazu , Endo Morito , Hamet Pavel , Tremblay Johanne
Published: October 2024

Oxidative stress mediated by reactive oxygen species (ROS) contributes to apoptosis of tubular epithelial cells (TECs) and renal inflammation during acute kidney injury (AKI). Copper Metabolism MURR1 domain-containing 5 (COMMD5/HCaRG) shows strong cytoprotective properties. COMMD5 is highly expressed in proximal tubules (PTs), where it controls cell differentiation. We assessed its role in cisplatin-induced AKI using transgenic mice in which COMMD5 is overexpressed in the PTs. Cisplatin caused the accumulation of damaged mitochondria and cellular waste in PTs, thus increasing the apoptosis of TECs. COMMD5 overexpression effectively protected TECs from cisplatin nephrotoxicity by decreasing intracellular ROS levels, mitochondrial dysfunction, and apoptosis through the preservation of tubular epithelial integrity, thus alleviating morphological and functional kidney damage. Excessive ROS production by hydrogen peroxide led to long-term autophagy activation through an increased burden on the autophagy/lysosome degradation system in TECs, and autophagic elimination of damaged mitochondria and cellular waste was compromised. COMMD5 attenuated oxidative injury by increasing autophagy flux, possibly due to a reduction of intracellular ROS levels through maintained tubular epithelial integrity, which decreased JNK/caspase-3-dependent apoptosis. Meanwhile, COMMD5 inhibition by small interfering RNA reduced the resistance of TECs to cisplatin cytotoxicity, as shown by disrupted tubular epithelial integrity and cell viability. These data indicated that COMMD5 protects TECs from drug-induced oxidative stress and toxicity by maintaining tubular epithelial integrity and autophagy flux and ultimately decreases mitochondrial dysfunction and apoptosis. Increasing COMMD5 content in PTs is proposed as a new protective and therapeutic strategy against AKI.
Effect of Cold Plasma‐Treated Turmeric on the Oxidative Stability and Quality of the Oil From the Milk Thistle Seeds
Authors: Samandari Kamyab , Fathi-Achachlouei Bahram , Azadmard-Damirchi Sodeif , Borhanian Jafar , Taghinezhad Ebrahim , Szumny Antoni
Published: October 2024

Many studies have been carried out on the antioxidant effects of medicinal plants in edible oils. One of those plants is turmeric, which, due to its biological and antioxidant compounds such as curcuminoids, has a strong antioxidant effect and prevents oxidation of unsaturated fatty acids (FAs). In this study, turmeric at different levels (5% and 10% w/w) was used to increase the oxidative stability of the milk thistle (Silybum marianum L.) seed oil (MTSO). Additionally, to improve the performance of turmeric, cold plasma (CP) treatment was used at different durations (5 and 10 min). The effect of turmeric on the quality parameters of MTSO was investigated during different storage times (1, 30, and 60 days). The results indicated that the addition of turmeric treated with CP significantly (p < 0.05) decreased the acidity value (AV) (1.00–0.62 mg NaOH/g oil) and the peroxide value (PV) (4.47–3.65 mEq O2/kg oil) and also increased the total phenolic content (1003.23–1116.90 mg/GAE/100 g oil), antioxidant activity, α‐tocopherol, and finally the oxidative stability compared to the control sample and oil containing untreated turmeric. Furthermore, gas chromatography (GC) analysis of the oil sample of the FA profile containing CP‐treated turmeric revealed the higher ratio of unsaturated FAs (i.e., linoleic and arachidonic acid) and lower saturated FA content (palmitic and stearic acid) compared to oil samples containing untreated turmeric. To conclude, CP treatment increased turmeric performance and improved the quality characteristics of MTSO.
Experimental Measurement and Modeling Analysis of the Heat Transfer in Graphene Oxide/Turbine Oil Non‐Newtonian Nanofluids
Authors: Esmaeili-Faraj S. H. , Bijhanmanesh M. J. , Alibak A. H. , Pirhoushyaran T. , Vaferi B.
Published: October 2024

Heat transfer characteristics of graphene oxide (GO)/turbine oil as a non‐Newtonian nanofluid are assessed both experimentally and numerically in this paper. To do so, 0.2, 0.3, 0.5, and 1 mass percent (wt%) of GO is homogeneously dispersed in the base liquid. First, the specific heat capacity, thermal conductivity, viscosity, and density of the synthesized nanofluids are measured using standard laboratory methods. After that, constants of the shear stress equation are determined through the nonlinear regression of the rheology data on the power law model. Finally, the heat transfer from turbine blades with a constant surface temperature to the coolant nanofluid is investigated using mathematical modeling. The results suggest that while the nanofluid density, viscosity, and thermal conductivity increase by increasing the nanoparticle concentration by 0.57%, 7.07%, and 18.89% in succession, respectively, and its specific heat capacity decreases by 0.54%. Moreover, both the convective heat transfer coefficient and the temperature profile in the considered nanofluids depend on the average velocity and Reynolds number. Furthermore, the convective heat transfer coefficient increases by 5.5%, 9.5%, 14%, and 17% in exchange for 0.2, 0.3, 0.5, and 1 wt% of GO nanoparticles in the base liquid, respectively.
Targeting NAD+ Metabolism Vulnerability in FH-Deficient Hereditary Leiomyomatosis and Renal Cell Carcinoma with the Novel NAMPT Inhibitor OT-82
Authors: Najera Susana S. , Ricketts Christopher J. , Schmidt Laura S. , Medina Julia I. , Saito Keita , Ileva Lilia , Brender Jeffrey R. , James Amy M. , Peer Cody J. , Gouker Brad , Karim Baktiar O. , Chernova Olga , Wells Catherine , Wei Ming-Hui , Yang Youfeng , Zhang Xiaohu , Klumpp-Thomas Carleen , Travers Jameson , Chen Lu , Wilson Kelli M. , Issaq Sameer H. , Figg William D. , Difilippantonio Simone , Kalen Joseph D. , Krishna Murali C. , Thomas Craig J. , Ceribelli Michele , Heske Christine M. , Crooks Daniel R. , Meier Jordan L.
Published: October 2024

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited cancer syndrome caused by germline pathogenic variants in the fumarate hydratase (FH) gene. Affected individuals are at risk for developing cutaneous and uterine leiomyomas and aggressive FH-deficient renal cell carcinoma (RCC) with a papillary histology. Due to a disrupted tricarboxylic acid cycle, FH-deficient kidney cancers rely on aerobic glycolysis for energy production, potentially creating compensatory metabolic vulnerabilities. This study conducted a high-throughput drug screen in HLRCC cell lines, which identified a critical dependency on nicotinamide adenine dinucleotide (NAD), a redox cofactor produced by the biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT). Human HLRCC tumors and HLRCC-derived cell lines exhibited elevated NAMPT expression compared with controls. FH-deficient HLRCC cells, but not FH-restored HLRCC or normal kidney cells, were sensitive to NAMPT inhibition. HLRCC cell line viability was significantly decreased in both 2D and 3D in vitro cultures in response to the clinically relevant NAMPT inhibitor OT-82. NAMPT inhibition in vitro significantly decreased the total amount of NAD+, NADH, NADP, NADPH, and poly-ADP-ribose levels, and the effects of NAMPT inhibition could be rescued by the downstream NAD precursor nicotinamide mononucleotide (NMN), confirming the on-target activity of OT-82. Moreover, NAMPT inhibition by OT-82 in two HLRCC xenograft models resulted in severely reduced tumor growth. OT-82 treatment of HLRCC xenograft tumors in vivo inhibited glycolytic flux as demonstrated by reduced lactate/pyruvate ratio in hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging experiments. Overall, our data define NAMPT inhibition as a potential therapeutic approach for FH-deficient HLRCC-associated RCC.
Supplementary Fig. 5 from Peroxisome Proliferator–Activated Receptor δ Suppresses the Cytotoxicity of CD8+ T Cells by Inhibiting RelA DNA-Binding Activity
Authors: Cen Bo , Wei Jie , Wang Dingzhi , DuBois Raymond N.
Published: October 2024

Supplementary Fig. 5 shows PPARδ inhibits RelA/p50 DNA binding activity.
Supplementary Fig. 4 from Peroxisome Proliferator–Activated Receptor δ Suppresses the Cytotoxicity of CD8+ T Cells by Inhibiting RelA DNA-Binding Activity
Authors: Cen Bo , Wei Jie , Wang Dingzhi , DuBois Raymond N.
Published: October 2024

Supplementary Fig. 4 shows the densitometric analysis of western blot results presented in Fig. 3.
Figure 3 from Peroxisome Proliferator–Activated Receptor δ Suppresses the Cytotoxicity of CD8+ T Cells by Inhibiting RelA DNA-Binding Activity
Authors: Cen Bo , Wei Jie , Wang Dingzhi , DuBois Raymond N.
Published: October 2024

PPARδ binds RelA and interferes with the RelA/p50 heterodimer formation. A, Interaction of RelA with PPARδ in nuclear extracts of human CTLs was revealed by two-way coimmunoprecipitations. B, RelA, p50, and PPARδ form a κB site-bound protein complex in human CTL nuclear extracts was revealed by EMSA and Western blot. C, Treating human CTLs with GW501516 (GW) enhances the interaction between RelA and PPARδ. D, PPARδ deficiency enhances the binding of p50 to RelA in human and mouse CTLs. E, Overexpression of PPARδ in human CTLs reduces the binding of p50 to RelA. F, Treatment of human CTLs with GW501516 (GW) reduces the binding of p50 to RelA. The results from C–F were obtained from coimmunoprecipitation assays. G, Reduced RelA binding to p50 in the presence of PPARδ in GST pulldown assay using purified proteins. Data are representative of three independent experiments with similar results.
Data from Peroxisome Proliferator–Activated Receptor δ Suppresses the Cytotoxicity of CD8+ T Cells by Inhibiting RelA DNA-Binding Activity
Authors: Cen Bo , Wei Jie , Wang Dingzhi , DuBois Raymond N.
Published: October 2024

Abstract
The molecular mechanisms regulating CD8+ cytotoxic T lymphocytes (CTL) are not fully understood. Here, we show that the peroxisome proliferator–activated receptor δ (PPARδ) suppresses CTL cytotoxicity by inhibiting RelA DNA binding. Treatment of ApcMin/+ mice with the PPARδ agonist GW501516 reduced the activation of normal and tumor-associated intestinal CD8+ T cells and increased intestinal adenoma burden. PPARδ knockout or knockdown in CTLs increased their cytotoxicity against colorectal cancer cells, whereas overexpression of PPARδ or agonist treatment decreased it. Correspondingly, perforin, granzyme B, and IFNγ protein and mRNA levels were higher in PPARδ knockout or knockdown CTLs and lower in PPARδ overexpressing or agonist-treated CTLs. Mechanistically, we found that PPARδ binds to RelA, interfering with RelA–p50 heterodimer formation in the nucleus, thereby inhibiting its DNA binding in CTLs. Thus, PPARδ is a critical regulator of CTL effector function.

Significance: Here, we provide the first direct evidence that PPARδ plays a critical role in suppressing the immune response against tumors by downregulating RelA DNA-binding activity. This results in decreased expression of perforin, granzyme B, and IFNγ. Thus, PPARδ may serve as a valuable target for developing future cancer immunotherapies.