bluuebunny/crossref_metadata_2025 huggingface dataset:
A red-emitting carborhodamine for monitoring and measuring membrane potential
Authors: Gest Anneliese M. M. , Lazzari-Dean Julia R. , Ortiz Gloria , Yaeger-Weiss Susanna K. , Boggess Steven C. , Miller Evan W.
Published: October 2023

Biological membrane potentials, or voltages, are a central facet of cellular life. Optical methods to visualize cellular membrane voltages with fluorescent indicators are an attractive complement to traditional electrode-based approaches, since imaging methods can be high throughput, less invasive, and provide more spatial resolution than electrodes.

Recently developed fluorescent indicators for voltage largely report changes in membrane voltage by monitoring voltage-dependent fluctuations in fluorescence intensity. However, it would be useful to be able to not only monitor changes, but also measure values of membrane potentials. This study discloses a new fluorescent indicator which can address both.

We describe the synthesis of a new sulfonated tetramethyl carborhodamine fluorophore. When thiscarborhodamine is conjugated with an electron-rich, methoxy (-OMe) containing phenylenevinylene molecular wire, the resulting molecule, CRhOMe, is a voltage-sensitive fluorophore with red/far-red fluorescence.

Using CRhOMe, changes in cellular membrane potential can be read out using fluorescence intensity or lifetime. In fluorescence intensity mode, CRhOMe tracks fast-spiking neuronal action potentials with greater signal-to-noise than state-of-the-art BeRST (another voltage-sensitive fluorophore). CRhOMe can also measure values of membrane potential. The fluorescence lifetime of CRhOMe follows a single exponential decay, substantially improving the quantification of membrane potential values using fluorescence lifetime imaging microscopy (FLIM). The combination of red-shifted excitation and emission, mono-exponential decay, and high voltage sensitivity enable fast FLIM recording of action potentials in cardiomyocytes. The ability to both monitor and measure membrane potentials with red light using CRhOMe makes it an important approach for studying biological voltages.

Significance Statement

Biological membrane potentials are maintained by all forms of life. In electrically excitable cells, fast changes in membrane potential drive downstream events: neurotransmitter release, contraction, or insulin secretion. The ability to monitor changes in and measure values of cellular membrane potentials is central to a mechanistic understanding of cellular physiology and disease. Traditional modes for measuring membrane potential use electrodes, which are invasive, destructive, low throughput, and ill-suited to interrogate spatial dynamics of membrane potentials. Optical methods to visualize potentials with fluorescent dyes offer a powerful complement to traditional electrode approaches. In this study, we show that a new, red to farred fluorophore can both monitor changes in and measure values of membrane potential in a variety of living systems.
GIRAFFOIDS FROM THE SIWALIKS OF PAKISTAN
Authors: Solounias Nikos , Ibáñez Maria Rios
Published: October 2023

Although today they occur in Africa, during the Miocene Giraffoids were widespread in Eurasia and Africa. We describe the giraffoid faunas found in the Siwaliks of Pakistan. These faunas are extremely rich in fossil mammals among which there are several new giraffoid taxa. In total, 28 species. They are an addition to taxa known before and give new insights in evolutionary relationships of all the taxa. Non-Siwalik localities that contribute key information are: Fort Ternan, Kalodirr, Tung Gur, Gebel Zelten, Gebel Hamrin and Bou Hanifia. (1) The Palaeomerycidae are distinct with ossicones and an occipital horn. The list of taxa includes five new Palaeomerycidae:Tauromeryx canteroinov. sp.,Nuchalia gratianov. gen. sp. nov.,Fovea fossatanov. gen. sp. nov.,Goniomeryx flynnigen. nov. sp. nov., andLateralia morganinov. gen. nov. sp. nov.; (2) new Climacoceridae:Vittoria soriaegen nov. sp nov.Orangemeryx badgleyinov. sp.Pachya moruorotigen. nov. sp. nov.Prolibytherium fusushas already been described. We also define two new ranks within the Climacoceridae family: the Climacocerinae and the Prolibytheriinae. (3) Preliminary systematics suggest that Giraffidae can be subdivided into two clades: the long and the short neck groups. The Siwaliks sample a total of fourteen different giraffids:Progiraffa exigua,Giraffokeryx punjabiensis,Ua pilbeami,Orea leptianew gen and new sp,Injanatherium hazimi,Giraffa punjabiensis, Giraffa sivalensis,Decennatherium asiaticum,Bramatherium megacephalum,Bramatherium perminese,Bamiscus microsnew gen and new sp., andSivatherium giganteum.Palaeotragus germaniifrom Bou Hanifia andBohlinia tungurensisfrom Tung Gur are new determinations. Progiraffinae and Bramatheriinae are new subfamilies of Giraffidae. The subfamilies of Giraffidae seem to hold as isolated evolutionary silos. Thus, they are hard to connect systematically. They are: Progiraffinae, Giraffokerycinae, Okapiinae, Bohlininae, Giraffinae, Palaeotraginae, Samotheriinae, Bramatheriinae and Sivatheriinae. It is hard to connect these subfamilies as they appear distinct around 16 Ma.
CH4transport in wetland plants under controlled environmental conditions – untangling the impacts of phenology
Authors: Ge Mengyu , Korrensalo Aino , Putkinen Anuliina , Laiho Raija , Kohl Lukas , Pihlatie Mari , Lohila Annalea , Makiranta Päivi , Siljanen Henri , Tuittila Eeva-Stiina , Koskinen Markku
Published: October 2023

Methane (CH4) fluxes at plant surfaces are the net result of transport of soil-produced CH4and within-plant CH4production and consumption, yet factors and processes controlling these fluxes remain unclear.

We conducted high-frequency automated CH4flux measurements from shoots ofCarex rostrata(sedge),Menyanthes trifoliata(forb) and shrubs (Betula nana,Salix lapponum) during early, high and late summer in a climate-controlled environment to assess the effects of environmental variables, seasonality and CH4 cycling microbes in the CH4 flux. Measurements were conducted from intact plant-soil samples collected throughout growing seasons 2020 and 2021 from Lompolojänkkäfen, northern Finland.

All studied species showed seasonal variability in CH4fluxes. The CH4 fluxes were not impacted by light level, while out of the studied species, porewater CH4concentration increased fluxes from all but B. nana. Air temperature only and negatively affected CH4 flux from C. rostrata. Both methanogens and methanotrophs were detected in aboveground parts ofS. lapponumandM. trifoliata, methanotrophs inB. nana, while neither were detected inC. rostrata.

Our study demonstrates that the seasonal phase of the plants regulates CH4 flux they mediate across species, which was not observed in the field. The detection of methanogens and methanotrophs in herbs and shrubs suggests that microbial processes may contribute to their CH4flux.
Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany
Authors: Joshi K , Scholz S , Maschio M , Kohli M , Lee A , Fust K , Ultsch B , van de Velde N , Beck E
Published: October 2023

Objectives

To assess the potential clinical impact and cost-effectiveness of coronavirus disease 2019 (COVID-19) mRNA vaccines updated for Autumn 2023 in adults aged ≥60 years and high-risk persons aged 30-59 years in Germany over a 1-year analytic time horizon (September 2023--August 2024).

Methods

A compartmental Susceptible-Exposed-Infected-Recovered model was updated and adapted to the German market. Numbers of symptomatic infections, number of COVID-19 related hospitalisations and deaths, costs, and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio of an Autumn 2023 Moderna updated COVID-19 (mRNA-1273.815) vaccine was compared to no additional vaccination. Potential differences between the mRNA-1273.815 and the Autumn Pfizer-BioNTech updated COVID-19 (XBB.1.5 BNT162b2) vaccines, as well as societal return on investment for the mRNA-1273.815 vaccine relative to no vaccination, were also examined.

Results

Compared to no Autumn vaccination, the mRNA-1273.815 campaign is predicted to prevent approximately 1,697,900 symptomatic infections, 85,400 hospitalisations, and 4,100 deaths. Compared to an XBB.1.5 BNT162b2 campaign, the mRNA-1273.815 campaign is also predicted to prevent approximately 90,100 symptomatic infections, 3,500 hospitalisations, and 160 deaths. Across both analyses we found the mRNA-1273.815 campaign to be dominant.

Conclusions

The mRNA-1273.815 vaccine can be considered cost-effective relative to the XBB.1.5 BNT162b2 vaccine and highly likely to provide more benefits and save costs compared to no vaccine in Germany, and to offer high societal return on investment.
Cognitive Processing Speed and Loneliness in Stroke Survivors: Insights from a Large-Scale Cohort Study
Authors: Byrne Christopher , Coetzer Rudi , Ramsey Richard
Published: October 2023

Objective

Loneliness, when prolonged, is associated with many deleterious effects and has been shown to be highly prevalent in those with a history of stroke, yet the cognitive mechanisms underpinning this phenomenon remain unclear. Therefore, the current study aims to investigate the extent to which cognitive factors, with specific focus on processing speed, are associated with loneliness in those with a history of stroke.

Method

Utilizing data from the British Cohort Study (BCS), a nationally representative dataset, we conducted secondary data analysis. A total of 7,752 participants completed relevant questions related to health, social interactions, demographics, loneliness, and cognitive assessments. Among them, 47 had experienced a stroke (“stroke,” n = 47), 5,545 reported other health conditions (“ill,” n = 5,545), and 2,857 were deemed healthy (“healthy,” n = 2,857)

Results

Consistent with previous research, our findings confirmed a positive correlation between stroke history and heightened loneliness. However, inferential analysis revealed that processing speed, alongside other cognitive factors, had a minimal impact on loneliness, with correlations too small to draw definitive conclusions.

Conclusion

This study suggests that cognitive processing speed alone is not a robust predictor of loneliness in stroke survivors. Consequently, when developing interventions to combat loneliness in this population, it is crucial to consider a broader spectrum of factors, such as social engagement, emotional well-being, and interpersonal relationships. This underscores the imperative need for comprehensive assessments to better comprehend the multifaceted nature of loneliness and inform more effective intervention strategies.
Delay of punishment highlights differential vulnerability to developing addiction-like behavior toward sweet food
Authors: Solinas Marcello , Lardeux Virginie , LeBlanc Pierre-Marie , Longueville Jean-Emmanuel , Thiriet Nathalie , Vandaele Youna , Panlilio Leigh , Jaafari Nematollah
Published: October 2023

Resistance to punishment is commonly used as a measure of compulsive behavior in addiction-related processes. We recently developed a progressive shock strength (PSS) procedure in which individual rats can titrate the amount of punishment that they are willing to tolerate to obtain food rewards. Here, we investigated the effects of a range of delays (0-12 sec) on resistance to punishment measured by PSS break points. As expected from delay discounting principles, we found that delayed shock was less effective as a punisher, as revealed by higher PSS breakpoints. However, this discounting effect was not equally distributed in the population of rats, and the introduction of a delay highlighted the existence of two populations: rats that were sensitive to immediate punishment were also weakly sensitive to delay, whereas rats that were resistant to immediate punishment showed strong temporal discounting of delayed punishment. Importantly, shock-sensitive rats suppressed responding even in non-punishment sessions, and they differed from shock-resistant rats in anxiety- like behavior but not in sensitivity to pain. These results show that manipulation of temporal contingencies of punishment in the PSS procedure provides a valuable tool to identify individuals with a double vulnerability to addiction: low sensitivity to aversion and excessive discounting of negative future consequences. Conversely, the shock-sensitive population may provide a model of humans who are vulnerable to opportunity loss due to excessive anxiety.
Decoding the molecular interplay of endogenous CD20 and Rituximab with fast volumetric nanoscopy
Authors: Ghosh Arindam , Meub Mara , Helmerich Dominic A. , Eiring Patrick , Kortüm K. Martin , Doose Sören , Sauer Markus
Published: October 2023

Elucidating the interaction between membrane proteins and antibodies requires fast whole-cell imaging at high spatiotemporal resolution. Lattice light-sheet (LLS) microscopy offers fast volumetric imaging but suffers from limited spatial resolution. DNA-PAINT achieves molecular resolution but is practically restricted to two-dimensional imaging due to long acquisition times. Here, we introduce two-dye imager (TDI) probes, manifesting negligible background and amplified fluorescence signal upon transient binding, enabling ∼15-fold faster imaging. Using a combination of TDI-DNA-PAINT and LLS microscopy on B cells, we reveal the oligomeric states and interaction of endogenous CD20 with the therapeutic monoclonal antibody rituximab (RTX), unperturbed by surface effects. Our results demonstrate that B cells become polarized, and microvilli stabilized by RTX binding. These findings, we believe, will aid rational design of improved immunotherapies targeting tumor-associated antigens.
Generalized Biomolecular Modeling and Design with RoseTTAFold All-Atom
Authors: Krishna Rohith , Wang Jue , Ahern Woody , Sturmfels Pascal , Venkatesh Preetham , Kalvet Indrek , Lee Gyu Rie , Morey-Burrows Felix S , Anishchenko Ivan , Humphreys Ian R , McHugh Ryan , Vafeados Dionne , Li Xinting , Sutherland George A , Hitchcock Andrew , Hunter C Neil , Baek Minkyung , DiMaio Frank , Baker David
Published: October 2023

Although AlphaFold2 (AF2) and RoseTTAFold (RF) have transformed structural biology by enabling high-accuracy protein structure modeling, they are unable to model covalent modifications or interactions with small molecules and other non-protein molecules that can play key roles in biological function. Here, we describe RoseTTAFold All-Atom (RFAA), a deep network capable of modeling full biological assemblies containing proteins, nucleic acids, small molecules, metals, and covalent modifications given the sequences of the polymers and the atomic bonded geometry of the small molecules and covalent modifications. Following training on structures of full biological assemblies in the Protein Data Bank (PDB), RFAA has comparable protein structure prediction accuracy to AF2, excellent performance in CAMEO for flexible backbone small molecule docking, and reasonable prediction accuracy for protein covalent modifications and assemblies of proteins with multiple nucleic acid chains and small molecules which, to our knowledge, no existing method can model simultaneously. By fine-tuning on diffusive denoising tasks, we develop RFdiffusion All-Atom (RFdiffusionAA), which generates binding pockets by directly building protein structures around small molecules and other non-protein molecules. Starting from random distributions of amino acid residues surrounding target small molecules, we design and experimentally validate proteins that bind the cardiac disease therapeutic digoxigenin, the enzymatic cofactor heme, and optically active bilin molecules with potential for expanding the range of wavelengths captured by photosynthesis. We anticipate that RFAA and RFdiffusionAA will be widely useful for modeling and designing complex biomolecular systems.
Link between lipid remodeling and ESCRT-III function in multivesicular body formation
Authors: Kölling Ralf
Published: October 2023

Despite a tremendous amount of work, it is still unclear how the endosomal sorting complex required for transport (ESCRT)-III complex acts in membrane remodeling and abscission. Here we present evidence that a change in membrane composition could be connected to ESCRT-III function during multivesicular body (MVB) formation. The central observation was a strong synergistic effect of two mutations on the turnover of an endocytic cargo protein. One mutation deletes Tms1, a yeast SERINC homologue. Human SERINC3 and SERINC5 are HIV-1 restriction factors and have been shown to act as scramblases, flipping phospholipids between membrane leaflets. The other mutation deletes the Vps68 subunit of the Vps55/Vps68 complex, which loosely resembles Tms1 in its overall structure. The strong synergistic effect suggests that Tms1 and Vps55/Vps68 perform a similar function. Since we could also show that Vps55 and Tms1 physically interact with ESCRT-III, we propose that a scramblase is recruited to ESCRT-III and plays a role in intraluminal vesicles formation at MVBs.
Nestlé (Dis)entangled! Braving the Maggi Noodle Crisis in India Part B
Authors: Chaudhri Vidhi , Kaul Asha
Published: October 2023

After a tumultuous five months, Nestle India was exonerated in the Maggi crisis just in time for Diwali. Although the mood was one of vindication, the leadership team with Suresh Narayanan at the helm, knew they faced a major challenge to regain lost glory. Stock price had plummeted along with consumer confidence which went down from over 90 to less than 5 per cent. Part B traces the efforts of Nestle India to not only reinforce the message of product quality but also to engage consumer trust. Through changes in product strategy, organizational structure, and multi-pronged communication, Maggi was able to rekindle the emotional connect with the consumer and surge back. On 30 November 2019 despite loss of market share, consumer faith and trust in 2015, Nestlé India was trading at INR 14,453/55 (NSE/BSE;~US$225) per share after hitting a record low of INR 4981 (~US$76) on 29 February 2016. Part B of the case outlines the measures Nestle India took to bounce back and asks if Nestle India's reputation out of the woods. Could the past come back to haunt Maggi or was the worst behind them? 1. Evaluate communication strategies available to organizations in a crisis situation. 2. Analyse the power and influence of consumer sentiment in reputation management.
International tourism development in the digital economy era: the role of ICT services and digital finance
Authors: Lee Chien-Chiang , Shi Jiayi , Zhang Hui , Wen Huwei
Published: October 2023

Purpose

This paper aims to investigate how information and communication technology (ICT) services and digital finance affect the development of international tourism.

Design/methodology/approach

The two-way fixed effect panel regression model, spatial econometric model, panel threshold regression model and panel quantile regression model are used. Data on tourism, economic and social development in 198 Chinese cities from 2011 to 2020 are analyzed.

Findings

This study finds that digital economy including ICT services and digital finance has significantly promoted the development of international tourism industry, while there is a negative spatial spillover effect. The promotion effect of international tourism increases significantly after digital innovation reaches the threshold value. International tourism is benefiting more from digital economy with the development of international tourism industry.

Research limitations/implications

The development quality of international tourism industry has not been analyzed due to data limitations, and the mechanism has not been tested.

Originality/value

This study creatively reveals the development of international tourism industry in the digital economy era from ICT services and digital finance perspectives. This study also shows the spatial, nonlinear and asymmetric relationship between digital economy and international tourism.
The relationship between mood and anxiety and cognitive phenotypes in adults with pharmacoresistant temporal lobe epilepsy
Authors: Bingaman Nolan , Ferguson Lisa , Thompson Nicolas , Reyes Anny , McDonald Carrie R. , Hermann Bruce P. , Arrotta Kayela , Busch Robyn M.
Published: October 2023

Objective

Patients with temporal lobe epilepsy (TLE) are often at a high risk for cognitive and psychiatric comorbidities. Several cognitive phenotypes have been identified in TLE, but it is unclear how phenotypes relate to psychiatric comorbidities, such as anxiety and depression. This observational study investigated the relationship between cognitive phenotypes and psychiatric symptomatology in TLE.

Methods

A total of 826 adults (age = 40.3, 55% female) with pharmacoresistant TLE completed a neuropsychological evaluation that included at least two measures from five cognitive domains to derive International Classification of Cognitive Disorders in Epilepsy (IC‐CoDE) cognitive phenotypes (i.e., intact, single‐domain impairment, bi‐domain impairment, generalized impairment). Participants also completed screening measures for depression and anxiety. Psychiatric history and medication data were extracted from electronic health records. Multivariable proportional odds logistic regression models examined the relationship between IC‐CoDE phenotypes and psychiatric variables after controlling for relevant covariates.

Results

Patients with elevated depressive symptoms had a greater odds of demonstrating increasingly worse cognitive phenotypes than patients without significant depressive symptomatology (odds ratio [OR] = 1.123–1.993, all corrected p's < .05). Number of psychotropic (OR = 1.584, p < .05) and anti‐seizure medications (OR = 1.507, p < .001), use of anti‐seizure medications with mood‐worsening effects (OR = 1.748, p = .005), and history of a psychiatric diagnosis (OR = 1.928, p < .05) also increased the odds of a more severe cognitive phenotype, while anxiety symptoms were unrelated.

Significance

This study demonstrates that psychiatric factors are not only associated with function in specific cognitive domains but also with the pattern and extent of deficits across cognitive domains. Results suggest that depressive symptoms and medications are strongly related to cognitive phenotype in adults with TLE and support the inclusion of these factors as diagnostic modifiers for cognitive phenotypes in future work. Longitudinal studies that incorporate neuroimaging findings are warranted to further our understanding of the complex relationships between cognition, mood, and seizures and to determine whether non‐pharmacologic treatment of mood symptoms alters cognitive phenotype.
Analysis of the Synchronous Response of Rotor Components by Wavelet Transform and Wavelet Probing
Authors: Carassale Luigi
Published: October 2023

The measured synchronous response of rotor components may be analyzed with two objectives. On the one hand, the estimation of the response amplitude is necessary for structural calculations such as the assessment of the low-cycle fatigue safety margin. On the other hand, it is used for system identification purpose with particular interest for damping. Both these tasks can be carried out efficiently and accurately using the time-frequency analysis (TFA) based on the continuous wavelet transform (WT). A major issue that limits a wide use of this tool is the lack of criteria to guide the analyst to a proper choice of the parameters involved in the wavelet transform. This paper discusses this problem from a theoretical and practical point of view and provides a criterion valid for the analysis of the response during resonance crossings.
Application of the Constrained Formulation to the Nonlinear Sloshing Problem Based on the Arbitrary Lagrangian–Eulerian Method
Authors: Hara Kensuke
Published: October 2023

This study deals with an application of constrained formulation to a nonlinear sloshing problem based on the arbitrary Lagrangian–Eulerian finite element method (ALE). The ALE method incorporates a discretized form of equations of motion with mesh updating algorithms in order to prevent a problem of mesh distortion. This paper focuses on an analytical aspect of such treatments as constrained systems in the formulation of the ALE method. Since the mesh updating algorithms give algebraic relations for nodal coordinates, this study treats these relations as constraints. Then, we introduce formulation for constrained systems based on the method of Lagrange multipliers. As a result of this formulation, equations of motion are given by differential algebraic equations (DAEs) consisting of differential equations for time evolution of physical quantities and algebraic equations (constraints). The present method can be classified into a kind of augmented formulation. Moreover, we present a size-reduction technique used in the Newton–Raphson method in order to remove a part of the redundant degrees-of-freedom in the iterative procedures, because the resulting set of DAEs involves a larger number of unknowns than the minimal number of degrees-of-freedom due to the introduction of the constrained formulation. The derived reduced system still holds the physically essential part of equations of motion for the sloshing problem. Even though it is not reduced to the minimal degrees-of-freedom, it does not involve algebraically complicated and inefficient procedures in computation. In addition, this study presents a method to introduce damping effects defined in the modal space into the FEM models. The proposed approach is validated by comparisons with experimental data in the time domain analysis.
Privacy-Preserving Neural Networks for Smart Manufacturing
Authors: Lee Hankang , Finke Daniel , Yang Hui
Published: October 2023

The rapid advance in sensing technology has expedited data-driven innovation in manufacturing by enabling the collection of large amounts of data from factories. Big data provides an unprecedented opportunity for smart decision-making in the manufacturing process. However, big data also attracts cyberattacks and makes manufacturing systems vulnerable due to the inherent value of sensitive information. The increasing integration of artificial intelligence (AI) within smart factories also exposes manufacturing equipment susceptible to cyber threats, posing a critical risk to the integrity of smart manufacturing systems. Cyberattacks targeting manufacturing data can result in considerable financial losses and severe business disruption. Therefore, there is an urgent need to develop AI models that incorporate privacy-preserving methods to protect sensitive information implicit in the models against model inversion attacks. Hence, this paper presents the development of a new approach called mosaic neuron perturbation (MNP) to preserve latent information in the framework of the AI model, ensuring differential privacy requirements while mitigating the risk of model inversion attacks. MNP is flexible to implement into AI models, balancing the trade-off between model performance and robustness against cyberattacks while being highly scalable for large-scale computing. Experimental results, based on real-world manufacturing data collected from the computer numerical control (CNC) turning process, demonstrate that the proposed method significantly improves the ability to prevent inversion attacks while maintaining high prediction performance. The MNP method shows strong potential for making manufacturing systems both smart and secure by addressing the risk of data breaches while preserving the quality of AI models.
Increasing Breast Support is Associated With a Distal-to-Proximal Redistribution of Joint Negative Work During a Double-Limb Landing Task
Authors: Fong Hailey B. , Nelson Alexis K. , McGhee Deirdre , Ford Kevin R. , Powell Douglas W.
Published: October 2023

Female athletes exhibit greater rates of anterior cruciate ligament injury compared with male athletes. Biomechanical factors are suggested to contribute to sex differences in injury rates. No previous investigation has evaluated the role of breast support on landing biomechanics. This study investigates the effect of breast support on joint negative work and joint contributions to total negative work during landing. Thirty-five female athletes performed 5 landing trials in 3 breast support conditions. Lower-extremity joint negative work and relative joint contributions to total negative work were calculated. Univariate analyses of variance were used to determine the effect of breast support on negative joint work values. Increasing levels of breast support were associated with lower ankle negative work (P < .001) and ankle relative contributions (P < .001) and increases in hip negative work (P = .008) and hip relative contributions (P < .001). No changes were observed in total negative work (P = .759), knee negative work (P = .059), or knee contributions to negative work (P = .094). These data demonstrate that the level of breast support affects lower-extremity biomechanics. The distal-to-proximal shift in negative joint work and relative joint contributions may be indicative of a more protective landing strategy for anterior cruciate ligament injuries.
Test–Retest Reliability of 3 Specific Strength Tests in Professional Handball Players
Authors: Morenas-Aguilar Maria Dolores , Chirosa Rios Luis J. , Rodriguez-Perea Angela , Vázquez Diz Juan Antonio , Chirosa Rios Ignacio J. , Vera Vera José Fernando , Ruiz-Orellana Lorenzo , Jerez-Mayorga Daniel
Published: October 2023

Context: Current devices to assess strength performance in handball may not be sufficiently sports-specific and reliable methods. Functional electromechanical dynamometry is a new technology that allows the development of accurate strength tests in athletes. Purpose: To determine the absolute and relative reliability and to compare the reliability of the right and left side, and mean and peak force of 3 specific strength tests in handball players with a functional electromechanical dynamometer: unilateral pullover, standing lift, and step forward. Methods: Fourteen male handball players of the first Spanish division (28.79 [4.81] y; 10.38 [4.63] y of professional experience) performed a repeated-measurement design. Three testing sessions were performed (one per week). The first measurement consisted of 4 isometric tests (right and left unilateral pullover, and right and left standing lift) to obtain isometric peak force, and in the second and third sessions, 6 incremental tests until failure (right and left unilateral pullover, and right and left standing lift, right and left step forward) were performed. Results: The tests provided high reliability or acceptable reliability for mean and peak strength of unilateral pullover, standing lift and step forward (intraclass correlation coefficient = .83–.97; coefficient of variation = 3.90–11.57). Effect side was negligible in any of the parameters, except for a small effect side in the left peak force for unilateral pullover and a small effect side on the left side for a step forward. Significant differences in reliability (coefficient of variation ratio > 1.15) were found between the right and left sides and peak and mean force in all exercises except peak force in unilateral pullover and step forward. Conclusion: These results confirm that the tests could be applied to assess physical performance in handball at the same time as regular gym training. Moreover, this is an excellent opportunity to individualize the player’s weekly load.
Temporal and geographic distribution of gut microbial enterotypes associated with host thermogenesis characteristics in plateau pikas
Authors: Tang Xianjiang , Zhang Liangzhi , Ren Shi'en , Zhao Yaqi , Zhang Yanming
Published: October 2023

Differentiation of the gut microbiota between individuals within a species can be identified by enterotypes. However, whether different enterotypes are associated with host-related physiological status and adaptation to specific habitats is still poorly understood. In this study, we collected 308 cecal samples from plateau pikas during varying seasons and altitudes. We identified three bacterial and two fungal enterotypes. The proportion of
Rikenellaceae_RC9_gut_group
- and
Prevotella
-predominated enterotype 3 was higher than that of the other two enterotypes in all samples. Enterotype 1, distinguished by norank
Muribaculaceae
, was mainly detected during the warm season and at high altitudes, whereas enterotype 2, which is unclassified
Lachnospiraceae
, was mainly detected during the cold season. Plateau pikas with bacterial enterotypes 2 and 3 showed significantly higher alpha diversity than those with enterotype 1, while pikas with fungal enterotype 1 displayed higher diversity than those with enterotype 2. Functional pathways of lipid metabolism were enriched in bacterial enterotype 1, carbohydrate and amino acid metabolism were enriched in enterotype 2, and energy metabolism was enriched in enterotype 3. The neutral process was more important in bacterial enterotype 3 than in enterotypes 1 and 2. The body temperature and resting metabolic rate of pikas with bacterial enterotypes 1 and 3 were significantly higher than those with enterotype 2. Pikas with unclassified
Sporormiaceae
- and
Sporormiella
-dominated fungal enterotypes may engage more frequently in coprophagy. Overall, this study revealed that both gut bacterial and fungal communities in pikas can be clustered into enterotypes, and individuals with different enterotypes showed significant differences in thermogenesis.

IMPORTANCE

The gut microbiotas of small mammals play an important role in host energy homeostasis. However, it is still unknown whether small mammals with different enterotypes show differences in thermogenesis characteristics. Our study confirmed that plateau pikas with different bacterial enterotypes harbored distinct thermogenesis capabilities and employed various strategies against cold environments. Additionally, we also found that pikas with different fungal enterotypes may display differences in coprophagy.
L-glutamine protects against enterohemorrhagic
Escherichia coli
infection by inhibiting bacterial virulence and enhancing host defense concurrently
Authors: Fang Fang , Xue Yunxin , Xu Xuefang , Fang Dingli , Liu Weijia , Zhong Ying , Han Jinping , Li Yunhe , Tao Qian , Lu Rong , Ma Cong , Kumar Arvind , Wang Dai
Published: October 2023

Enterohemorrhagic
Escherichia coli
(EHEC) can colonize the gastrointestinal tract and cause bloody diarrhea in children. Previous studies showed that its pathogenesis could be mediated by metabolites from both the host and microbiota. L-Glutamine (Gln) was found to be depleted in intestinal tissues as the main energy source according to previous studies. Hence, we aimed to determine the effects of Gln on EHEC infection and its underlying mode of action. In this study, a Gln-limited signal was found to activate the type 3 secretion system (T3SS), which is crucial for EHEC infection
via
perturbation of central metabolism. By shifting the phosphorylation of NtrC, a key regulator in bacterial nitrogen metabolism, Gln stimulates
ler
transcripts in a σ
S
-PchA-dependent manner. Our
in vivo
experiments further demonstrated that Gln supplementation can reduce EHEC colonization in the gastrointestinal tract by repressing T3SS. Moreover, Gln could further attenuate bacterial infection by boosting host defense, which might be dependent on multiple pathways. Besides, our experiments demonstrated that Gln did not induce Shiga-like toxin (Stx) production or cause impairment of gut flora. In conclusion, our study presented evidence that Gln could act against EHEC infection by reducing bacterial virulence and strengthening host defense. Therefore, Gln serves as a promising therapeutic agent for EHEC infection.

IMPORTANCE

The type 3 secretion system (T3SS) was obtained in many Gram-negative bacterial pathogens, and it is crucial for their pathogenesis. Environmental signals were found to be involved in the expression regulation of T3SS, which was vital for successful bacterial infection in the host. Here, we discovered that L-glutamine (Gln), the most abundant amino acid in the human body, could repress enterohemorrhagic
Escherichia coli
(EHEC) T3SS expression
via
nitrogen metabolism and therefore had potential as an antivirulence agent. Our
in vitro
and
in vivo
evidence demonstrated that Gln could decline EHEC infection by attenuating bacterial virulence and enhancing host defense simultaneously. We repurpose Gln as a potential treatment for EHEC infection accordingly.
Characterization of T-cell subsets in response to foot-and-mouth disease bivalent inactivated vaccine in Chinese Holstein cows
Authors: Zhang Zhipeng , Wang Dasheng , Yao Yiyang , Yang Jiayu , Yang Zhangping , Yang Yi
Published: October 2023

Traditional vaccine efficacy evaluation predominantly relies on antibody levels, while the assessment of T-cell responses remains underexplored. In this study, we employed multi-parameter flow cytometry to comprehensively analyze T-cell responses in cows vaccinated against foot-and-mouth disease (FMD). We categorized the cows into high and low vaccine potency groups based on antibody levels and investigated differences in T-cell responses between these groups. Phenotypic analysis revealed a significant reduction in CD4, CD8, and γδ T cells in peripheral blood following FMD vaccine inoculation, concomitant with altered CD44 expression. Intriguingly, FMD vaccination induced a marked increase in the percentage of CD4
+
CD8
+
double-positive (DP) T cells in cow peripheral blood. Notably, cows with high vaccine potency exhibited a significantly higher proportion of CD4
+
CD8
+
DP T cells compared to those with low potency post-vaccination, suggesting their potential involvement in FMD vaccine-induced immune protection, possibly through the regulation of B-cell antibody secretion. Additionally, FMD vaccination led to the generation of central memory CD4 and CD8 T cells but not γδ T cells. Our groundbreaking findings shed light on the latent function of CD4
+
CD8
+
DP T cells in FMD vaccine-induced immune protection and established a novel method for evaluating FMD vaccine efficacy based on T-cell responses.

IMPORTANCE

Vaccination plays a crucial role in the prevention and control of FMD; however, outbreaks persist occurring worldwide. Assessing the immune response to FMD vaccines is essential for effective prevention of FMD. In this study, a seven-color flow cytometry protocol was developed to systematically evaluate the T-cell response of Chinese Holstein cows vaccinated with FMD bivalent inactivated vaccine. Our findings showed that while most T-cell subsets (%) decreased post-vaccination, a significant increase was observed in CD4
+
CD8
+
DP T cells, which was consistent with the levels of specific foot-and-mouth disease virus (FMDV) antibodies. These findings suggested that CD4
+
CD8
+
DP T cells could serve as a potential biomarker for the evaluation of cellular and humoral responses to FMDV vaccination. Additionally, we should be aware of the potential decline in cellular immunity among cattle during FMD vaccination, as this may increase the risk of other pathogen-related issues.
Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles
Authors: Oberholster Larise , Mathias Amandine , Perriot Sylvain , Blaser Emma , Canales Mathieu , Jones Samuel , Culebras Lucas , Gimenez Marie , Kaynor G. Campbell , Sapozhnik Alexey , Richetin Kevin , Goelz Susan , Du Pasquier Renaud
Published: October 2023

JC polyomavirus (JCPyV) is an opportunistic virus that remains in a latent state in the kidneys and lymphoid organs of more than half of the human adult population. In rare cases of severe immune suppression, the virus is able to establish a lytic infection of glial cells in the brain, resulting in a debilitating, demyelinating disease known as progressive multifocal leukoencephalopathy (PML). Because of the exceptional species and tissue specificity of the virus, appropriate models of JCPyV infection in the brain are lacking, thus hampering progress toward the development of novel antiviral strategies and biomarkers of disease activity. While PML has traditionally been characterized as a lytic infection of oligodendrocytes, more recent findings suggest an important role for astrocytes during the initial stages of disease. Here, using human-induced pluripotent stem cell (hiPSC)-derived astrocytes coupled with a multiparametric approach, we show that (i) JCPyV readily infects and replicates in astrocytes, (ii) JCPyV strongly dysregulates the cell biology, and (iii) these results adequately reflect
ex vivo
findings. We perform an in-depth characterization of the effect of JCPyV on the cell proteome over time, demonstrating a strong dysregulation of the cell cycle and activation of the DNA damage response. Furthermore, we show that the proteomic signature observed for infected astrocytes is extended to extracellular vesicles, underlining their potential as a resource to gain valuable insights into JCPyV infection in the brain.

IMPORTANCE

Progressive multifocal leukoencephalopathy is a crimpling demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV). Much about JCPyV propagation in the brain remains obscure because of a lack of proper animal models to study the virus in the context of the disease, thus hampering efforts toward the development of new antiviral strategies. Here, having established a robust and representative model of JCPyV infection in human-induced pluripotent stem cell-derived astrocytes, we are able to fully characterize the effect of JCPyV on the biology of the cells and show that the proteomic signature observed for JCPyV-infected astrocytes is extended to extracellular vesicles (EVs). These data suggest that astrocyte-derived EVs found in body fluids might serve as a rich source of information relevant to JCPyV infection in the brain, opening avenues toward better understanding the pathogenesis of the virus and, ultimately, the identification of new antiviral targets.
Predictors of and healthcare utilisation of depressive symptoms among middle-aged and older adults in Thailand: a national cross-sectional community-based study in 2015
Authors: Kengganpanich Mondha , Pengpid Supa , Peltzer Karl
Published: October 2023

Objective

The prevalence of depressive symptoms and healthcare utilisation among the ageing population in Thailand is unclear. The study assessed the predictors of and healthcare utilisation of depressive symptoms among an ageing population in Thailand.

Design

Cross-sectional, population-based study.

Setting

National sample of people aged 45 years and older in Thailand from the 2015 Health, Ageing and Retirement in Thailand (HART) study.

Participants

The sample included 5135 individuals (≥45 years) with complete depressive symptoms data from the 2015 HART study.

Outcome measures

Depressive symptoms were measured with the Centre for Epidemiological Studies Depression Scale. Logistic regression was used to estimate the associations between sociodemographic factors, health factors and depressive symptoms, and the associations between depressive symptoms and different types of healthcare utilisation.

Results

The study population included 5135 participants with a median age of 66 years. The prevalence of depressive symptoms was 13.9%. The proportion of past 2 year hospital admission was 12.8%, hospital outpatient 49.7%, health centre outpatient 26.2%, private clinic 8.4%, traditional medical practitioner 2.8%, medical home visit 4.9% and past-year medical check-up 50.3%. In adjusted logistic regression analysis, low income, residing in the Southern region, history of a cardiovascular disease, brain diseases and/or psychiatric problems and functional disability were positively associated with depressive symptoms. Male sex, being a Buddhist, urban residence, high religious involvement, moderate and high physical activity were negatively associated with depressive symptoms. In fully adjusted logistic regression models, depressive symptoms were positively associated with hospital inpatient utilisation, hospital outpatient utilisation, health centre utilisation and utilisation of a traditional medicine practitioner.

Conclusions

More than one in 10 participants had depressive symptoms. Chronic conditions, sociodemographic factors, physical inactivity and low religious involvement increased the odds of depressive symptoms. Furthermore, depressive symptoms increased the odds of conventional and traditional healthcare utilisation.
Equity in health service utilisation among middle-aged and elderly people with multiple chronic conditions in China: evidence from longitudinal data of 2011–2018 CHARLS
Authors: Zhang Tianjiao , Su Min , Li Dongxu , Zhang Weile , Yang Fan , Li Wenhui
Published: October 2023

Objectives

Equity in health service utilisation is a central objective for health systems. Middle-aged and elderly patients with multiple chronic conditions (MCCs) are particularly vulnerable to healthcare inequity. This study aimed to update the information on the trends in the incidence and equity of outpatient health service utilisation (OHSU) and inpatient health service utilisation (IHSU) for middle-aged and elderly MCCs patients in China, identify socioeconomic determinants that may contribute to inequity, and suggest optimisation strategies to mitigate this disparity.

Methods

Panel data obtained from four waves of the China Health and Retirement Longitudinal Study (CHARLS) were used to determine the trends in OHSU and IHSU. The inequity in OHSU and IHSU was measured by the Concentration Index (CI) and Horizontal Inequity Index (HI), which is a valid measure of health service utilisation equity. The decomposition model of the CI was set up to explore the contribution of various determinants of overall equity.

Results

The annual rate of OHSU gradually decreased from 29.32% in 2011 to 27.27% in 2018. The HI remained positive and decreased from 0.0803 in 2011 to 0.0662 in 2018, indicating the existence of pro-rich inequity. The annual rate of IHSU gradually increased from 13.31% in 2011 to 19.89% in 2018. The HI remained positive and showed a declining trend from 0.2363 in 2011 to 0.0574 in 2018, evidencing pro-rich inequity; however, a trend towards the easing of inequity was observed.

Conclusions

Pro-rich inequity was present in both OHSU and IHSU among middle-aged and elderly MCCs patients in China. Economic status, area, education and age were the main contributors to pro-rich inequity. Concerted efforts are needed to allocate resources for mitigating health service utilisation inequity in middle-aged and elderly people with MCCs.