bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the capacity of several machine learning tools to assist immunofluorescence-based detection of anti-neutrophil cytoplasmic antibodies
Authors: Bertin Daniel , Bongrand Pierre , Bardin Nathalie
Published: January 2024

The success of artificial intelligence and machine learning is an incentive to develop new algorithms to increase the rapidity and reliability of medical diagnosis. Here we compared different strategies aimed at processing microscope images used to detect anti-neutrophil cytoplasmic antibodies, an important vasculitis marker: (i) basic classifier methods (logistic regression, k-nearest neighbors and decision tree) were used to process custom-made indices derived from immunofluorescence images yielded by 137 sera. (ii) These methods were combined with dimensional reduction to analyze 1733 individual cell images. iii) More complex models based on neural networks were used to analyze the same dataset. The efficiency of discriminating between positive and negative samples and different fluorescence patterns was quantified with Rand-type accuracy index, kappa index and ROC curve. It is concluded that basic models trained on a limited dataset allowed positive/negative discrimination with an efficiency comparable to that obtained by conventional analysis performed by humans (0.84 kappa score). More extensive datasets may be required for efficient discrimination between different fluorescence patterns generated by different auto-antibody species.
Feeling at Home in a Virtually Amputated Body; Neural and Phenomenological Effects of Illusory Embodiment in Body Integrity Dysphoria
Authors: Saetta Gianluca , Peter Yannik , Ruddy Kathy , Ho Jasmine T. , Luechinger Roger , Cross Emily , Michels Lars , Lenggenhager Bigna
Published: January 2024

In Body Integrity Dysphoria (BID) a profound incongruity between the physical body and the desired, i.e., amputated body, often leads to a desire for limb amputation. Virtual reality (VR) and multisensory stimulation paradigms provide powerful tools to create the experience of being embodied in an amputated body.

Here we investigate the impact of such an experience on neural and subjective responses in 18 individuals with BID and 18 controls. We used both task-based and resting-state MRI before and after participants played an immersive virtual game in an amputated body corresponding to their desired bodily shape and mimicking their movements. The task-based fMRI assessed neural activity when viewing images of the body in the desired versus the undesired state.

Individuals with BID reported higher sense of ownership and control over the virtual body. Task-based fMRI showed increased pre-VR activity in the right superior parietal lobule (rSPL), right angular gyrus, and right supplementary motor area in the BID group, normalizing after VR exposure. Resting-state fMRI showed reduced connectivity in the rSPL, visuo-occipital areas, fronto-parietal, and fronto-striatal mirror and limb system networks, also normalising post-VR. Additionally, there was a normalization in the pattern of increased connectivity of cortico-striatal tracts connecting the rSPL and the pars orbitalis of the right inferior frontal gyrus with the nucleus accumbens.

Our findings suggest that virtual embodiment effectively modulates BID-related neural networks, offering a safe, cost-effective intervention for BID and highlights VR’s potential in exploring the complex interaction between body and self, with potential implications for similar psychiatric conditions.
Implementation of Community Health Worker Support for Tobacco Cessation: A Mixed-Methods Study
Authors: Foo Cheryl Y. S. , Potter Kevin , Nielsen Lindsay , Rohila Aarushi , Maravic Melissa Culhane , Schnitzer Kristina , Pachas Gladys N. , Levy Douglas E. , Reyering Sally , Thorndike Anne N. , Cather Corinne , Evins A. Eden
Published: January 2024

Objective

Adults with serious mental illness have high tobacco use disorder rates and underutilization of first-line tobacco cessation pharmacotherapy. In a randomized trial, participants offered community health worker (CHW) support and primary care provider (PCP) education had higher tobacco abstinence rates at two years, partly through increased tobacco cessation pharmacotherapy initiation. This study determined the association between participant-CHW engagement and tobacco abstinence outcomes.

Methods

This was a secondary, mixed-methods analysis of 196 participants in the trial’s intervention arm. Effects of CHW visit number and duration, CHW co-led smoking cessation group sessions attended, and CHW-attended PCP visit number on tobacco use disorder pharmacotherapy initiation and tobacco abstinence were modeled using logistic regression. Interviews with 12 CHWs, 16 participants, and 17 PCPs were analyzed thematically.

Results

Year-two tobacco abstinence was associated with CHW visit number (OR=1.85, 95% CI=[1.29, 2.66]) and duration (OR=1.85, 95% CI=[1.33, 2.58]) and number of groups attended (OR=1.51, 95% CI=[1.00, 2.28]); effects on pharmacotherapy initiation were similar. 1-3 CHW visits per month over two years was optimal for achieving abstinence. Interviews identified engagement facilitators, including CHWs establishing trust, providing goal accountability, skills reinforcement, and assistance overcoming barriers to treatment access and adherence related to social determinants of health and illness factors. Robust training and supervision facilitated CHW effectiveness. Barriers included PCPs’ and care teams’ limited understanding of the CHW role.

Conclusions

Feasible CHW engagement was associated with tobacco abstinence in adults with serious mental illness. CHW implementation may benefit from promoting CHW training and integration within clinical teams.

Highlights

Greater participant engagement with community health workers (CHWs) (e.g., visit number, duration) was associated with higher tobacco abstinence rates in a two-year intervention for adults with serious mental illness and tobacco use disorder.

Interviews with participants, CHWs, and primary care providers (PCPs) indicated that CHWs built trust, facilitated health behavior change, helped participants overcome adverse social determinants of health and other barriers to obtaining effective tobacco use disorder treatment.

Training and supervision were perceived to be essential to CHW effectiveness; CHWs and PCPs suggested insufficient integration of CHWs into psychiatric rehabilitation and healthcare teams as an addressable implementation barrier.
Determinants of Hepatitis B Viral infection among pregnant women in Greater Monrovia, Liberia
Authors: Kohar Henry Torbandu , Adu George Asumah , Addo Henry Ofosu , Afari Edwin , Kenu Ernest , Wurapa Frederick
Published: January 2024

Background

The global prevalence of hepatitis B virus infection is estimated to affect over 2 billion individuals, with a notable proportion ranging from 6% to 25% residing in the Sub-Saharan African region. The prevalence of hepatitis B virus (HBV) in Liberia, Guinea, and Sierra Leone has been estimated to be approximately 2%. However, current understanding of the actual risk factors associated with HBV in the Greater Monrovia remains unclear. Consequently, this study aimed to identify the factors associated with hepatitis B Viral infection among pregnant women residing in Greater Monrovia, Liberia.

Methods

An unmatched case control study of 141 cases of HBV infected pregnant women and 141 controls was conducted. Data on socio-demographic characteristics, lifestyle activities and medical related risk factors were collected for both groups with a structured questionnaire. Bivariate and multivariate analyses established associations between the HBV infection and risk factors studied.

Results

In all, 141 cases of HBV infected pregnant women and 141 controls participated in this study. The mean age of cases was 35.6 years (SD ±9.5) and 36.1 years (SD ±8.4) for controls. Low-income level <100 dollars [aOR 13.0 (4.48-37.82, p<0.001)], employment [aOR 0.04 (0.09-0.18) p<0.001], STI history [aOR 5.19 (1.68-16.02, p=0.004)] and living with a HBV infected person [aOR 35.11 (4.24-58.90), p=0.001] were factors associated with HBV infection among pregnant women in Greater Monrovia.

Conclusion

The risk factors of HBV infection among pregnant women in Greater Monrovia were engagement in formal employment, low-income level, history of sexually transmitted infections (STIs), and residing with an individual infected with hepatitis B virus (HBV). Control efforts by designated state institutions should include advocacy and awareness creation on HBV status identification, safe sex, and vaccination of uninfected individuals.
Mitotic Activity and DNA Maintenance of Adult Neural Stem Cells is Regulated by Beclin1
Authors: Kalinina A. , Dhaliwal J. , Xue Y , Vaculik M. , McCambley M. , Fong B.C. , Cook D. , Slack R.S. , Lagace D.C.
Published: January 2024

Beclin1 is a tumor suppressor gene that can regulate proliferation under pathological conditions. Whether Beclin1 has a role in regulating proliferation in physiological conditions remains unknown. Here, through the creation of an inducible transgenic mouse that removes Beclin1 from adult neural stem and progenitor cells (NSPCs) and their progeny we uncovered that Beclin1 is required cell-autonomously to sustain proliferating NSCPsin vivoandex vivo. Flow cytometry analysis and single-cell RNA-sequencing show that Beclin1 is required for mitosis. Additional analysis of the proliferating NSPCs resolved by stage of cell cycle uncovered that Beclin1-null cells have a distinct differential developmental trajectory accompanied by downregulation of genes involved in chromosomal maintenance and upregulation of cell stress genes upon cell cycle exit. These effects align with DNA damage in Beclin1-null cells and ultimately result in less adult-born granular neurons. Together these data identify Beclin1 as a novel regulator of mitosis in adult NSPCs.
Queen loss fails to elicit physiological and transcriptional responses in workers of the invasive garden antLasius neglectus
Authors: Majoe Megha , Stolarek Nicole , Vizueta Joel , Xiong Zijun , Schrader Lukas , Boomsma Jacobus J. , Foitzik Susanne , Libbrecht Romain , Nehring Volker
Published: January 2024

Insect colonies with morphologically distinct castes have been called superorganisms because their queens and workers are functionally analogous to the germline and soma in metazoan bodies. In the haplodiploid ants, workers typically lost the sperm storage organ but retained ovaries so they can lay unfertilized eggs. Worker reproduction often occurs after queen loss and is accompanied by a number of physiological changes. However, in some evolutionarily derived ants, workers have become functionally sterile and in many of these species colonies contain multiple queens and can readily raise replacement queens - a syndrome characteristic for invasive ants. We hypothesized that the combination of full worker sterility and regular queen replacement should have eliminated important aspects of the physiological interdependence between queens and workers. We tested this hypothesis by analysing fat body gene expression and worker resistance to oxidative stress in colonies of the invasive antLasius neglectuswith and without queens. We found age-related transcriptional shifts between young and old queens and young and old workers, suggesting rapid ageing in all castes. However, the removal of any queens in controlled experiments failed to elicit changes in the transcriptional activity and oxidative stress resistance of workers, consistent with our hypothesis. The invasive syndrome of this ant may thus have led to a somatic work force that evolved to be physiologically independent of queen presence.
Drawings reveal changes in object memory, but not spatial memory, across time
Authors: Megla Emma , Rosenthal Samuel R. , Bainbridge Wilma A.
Published: January 2024

Time has an immense influence on our memory. Truncated encoding leads to memory for only the ‘gist’ of an image, and long delays before recall result in generalized memories with few details. Here, we used crowdsourced scoring of hundreds of drawings made from memory after variable encoding (Experiment 1) and retentions of that memory (Experiment 2) to quantify what features of memory content change across time. We found that whereas some features of memory are highly dependent on time, such as the proportion of objects recalled from a scene and false recall for objects not in the original image, spatial memory was highly accurate and relatively independent of time. We also found that we could predict which objects were recalled across time based on the location, meaning, and saliency of the objects. The differential impact of time on object and spatial memory supports a separation of these memory systems.
From Brownian to deterministic motor movement in a DNA-based molecular rotor
Authors: Rothfischer Florian , Vogt Matthias , Kopperger Enzo , Gerland Ulrich , Simmel Friedrich C.
Published: January 2024

Molecular devices that have an anisotropic, periodic potential landscape can be operated as Brownian motors. When the potential landscape is cyclically switched with a chemical reaction or an external force, such devices can harness random Brownian fluctuations to generate directed motion. Recently, directed Brownian motor-like rotatory movement was demonstrated with an electrically switched DNA origami rotor with designed, ratchet-like obstacles. Here, we demonstrate that also the intrinsic anisotropy of DNA origami rotors that originally were not designed as Brownian motor devices is sufficient to result in motor movement. We show that for low amplitudes of an external switching field such devices operate as Brownian motors, while at higher amplitudes the movement is better described by the deterministic motion of an overdamped electrical motor. We characterize the amplitude and frequency dependence of the movements in both regimes, showing that after an initial steep rise the angular speed peaks and drops for excessive driving amplitudes and frequencies. The characteristics of the rotor movement are well described by a simple stochastic model of the system.
C1QA is an invariant biomarker for tissue macrophages
Authors: Horowitz Amir , Yu Haocheng , Pandey Sonalisa , Mishra Bud , Sahoo Debashis
Published: January 2024

Macrophages play a pivotal role in immune responses, particularly in the context of combating microbial threats within tissues. The identification of reliable biomarkers associated with macrophage function is essential for understanding their diverse roles in host defense. This study investigates the potential of C1QA as an invariant biomarker for tissue macrophages, focusing on its correlation with the anti-microbial pathway. C1QA, a component of the complement system, has been previously implicated in various immune functions. Our research delves into the specific association of C1QA with tissue-resident macrophages and its implications in the context of anti-microbial responses. Through comprehensive systems biology and Boolean analysis of gene expression, we aim to establish C1QA as a consistent and reliable marker for identifying tissue macrophages. Furthermore, we explore the functional significance of C1QA in the anti-microbial pathway. This research seeks to provide valuable insights into the molecular mechanisms underlying the anti-microbial functions of tissue macrophages, with C1QA emerging as a potential key player in this intricate regulatory network. Understanding the relationship between C1QA, tissue macrophages, and the anti-microbial pathway could pave the way for the development of targeted therapeutic strategies aimed at enhancing the host’s ability to combat infections. Ultimately, our findings contribute to the expanding knowledge of macrophage biology and may have implications for the diagnosis and treatment of infectious diseases.

One Sentence Summary

C1QA is a fundamental biomarker of tissue macrophages
Early-stage cancer results in a multiplicative increase in cell-free DNA originating from healthy tissue
Authors: Mamis Konstantinos , Bozic Ivana
Published: January 2024

Cell-free DNA (cfDNA) is a promising biomarker for cancer detection. However, cfDNA dynamics in the presence of cancer are still poorly understood. Leveraging a rich dataset of cfDNA in healthy individuals and early-stage cancer patients, we find a multiplicative increase in cfDNA concentration in the presence of cancer. This increase is cancer type-specific, ranging from a ∼1.3-fold increase in lung cancer, to a ∼12-fold increase in liver cancer, and does not originate from tumor, but from healthy tissue. Employing an additional dataset reporting the tissue of origin of cfDNA, we observe a significant increase in the correlation between cfDNA originating from leukocytes and from non-leukocyte sources in cancer patients. Introducing a mathematical model for cfDNA dynamics, we find that the observed correlation can be explained by a saturation mechanism in cfDNA clearance. Saturation in clearance implies that smaller increases in cfDNA shedding from healthy tissue due to cancer may lead to the larger observed multiplicative increases in cfDNA levels.
Association of sepsis and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage
Authors: Centner Franz-Simon , Wenz Holger , Oster Mariella Eliana , Dally Franz-Joseph , Sauter-Servaes Johannes , Pelzer Tanja , Schoettler Jochen Johannes , Hahn Bianka , Abdulazim Amr , Hackenberg Katharina Antonia Margarete , Groden Christoph , Krebs Joerg , Thiel Manfred , Etminan Nima , Maros Máté Elod
Published: January 2024

Background

Although sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association of sepsis with DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition.

Methods

Patients admitted to our hospital between 11/2014-11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0-3 vs. 4-6). Propensity score matching (PSM) and multivariable logistic regressions were performed.

Results

Of 238 patients with aSAH, 55 (23%) developed sepsis and 74 (31%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p<0.01) and longer ICU stay (p=0.046). Sepsis was independently associated with DCI (OR=2.46, 95%CI: 1.28-4.72, p<0.01). However, after exclusion of patients who developed sepsis before (OR=1.59, 95%CI: 0.78-3.24, p=0.21) or after DCI (OR=0.85, 95%CI: 0.37-1.95, p=0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56% (76/135) in patients with neither sepsis nor DCI, to 43% (21/48) in those with no sepsis but DCI, to 34% (10/29) with sepsis but no DCI and to 8% (2/26) in patients with both sepsis and DCI.

Conclusions

Our study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies.
Increased regional P2X7R uptake detected by [18F]GSK1482160 PET in a tauopathy mouse model
Authors: Kong Yanyan , Cao Lei , Wang Jiao , Zhuang Junyi , Liu Yongshan , Bi Lei , Qiu Yifan , Hou Yuyi , Huang Qi , Xie Fang , Yang Yunhao , Shi Kuangyu , Rominger Axel , Guan Yihui , Jin Hongjun , Ni Ruiqing
Published: January 2024

Neuroinflammation plays an important role in Alzheimer’s disease and primary tauopathies. The aim of the current study was to map [18F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer’s disease and primary tauopathy mouse models. MicroPET was performed using [18F]GSK1482160 in widely used mouse models of Alzheimer’s disease (APP/PS1, 5×FAD and 3×Tg), 4-repeat tauopathy (rTg4510) mice and age-matched wild-type mice. Increased uptake of [18F]GSK1482160 was observed in the cortex and basal forebrain of 7-month-old rTg4510 mice compared to age-matched wild-type mice and compared to 3-month-old rTg4510 mice. Nonparametric Spearman’s rank analysis revealed a positive correlation between tau [18F]APN-1607 uptake and [18F]GSK1482160 in the hippocampus of rTg4510 mice. No significant differences in the uptake of [18F]GSK1482160 were observed between wild-type mice and APP/PS1 mice (5, 10 months), 5×FAD mice (3, 7 months) or 3×Tg mice (10 months). Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion compared to wild-type mice. These findings provide in vivo imaging evidence for increased P2X7R in the brains of tauopathy model mice.
Reduced Proactive and Reactive Cognitive Flexibility in Older Adults Underlies Performance Costs During Dual-Task Walking: A Mobile Brain/Body Imaging (MoBI) Study
Authors: Richardson David P. , Foxe John J. , Freedman Edward G.
Published: January 2024

Age-related reductions in cognitive flexibility may limit modulation of control processes during systematic increases to cognitive-motor demands, exacerbating dual-task costs. In this study, behavioral and neurophysiologic changes to proactive and reactive control during progressive cognitive-motor demands were compared across older and younger adults to explore the basis for age-differences in cognitive-motor interference (CMI). 19 younger (19 - 29 years old, mean age = 22.84 +/- 2.75 years, 6 male, 13 female) and 18 older (60 - 77 years old, mean age = 67.89 +/- 4.60 years, 9 male, 9 female) healthy adults completed cued task-switching while alternating between sitting and walking on a treadmill. Gait kinematics, task performance measures, and brain activity were recorded using electroencephalography (EEG) based Mobile Brain/Body Imaging (MoBI). Response accuracy on easier trial types improved in younger, but not older adults when they walked while performing the cognitive task. As difficulty increased, walking provoked accuracy costs in older, but not younger adults. Both groups registered faster responses and reduced gait variability during dual-task walking. Older adults exhibited lower amplitude modulations of proactive and reactive neural activity as cognitive-motor demands systematically increased, which may reflect reduced flexibility for progressive preparatory and reactive adjustments over behavioral control.
Efficient enzyme-free isolation of brain-derived extracellular vesicles
Authors: Matamoros-Angles A. , Karadjuzovic E. , Mohammadi B. , Song F. , Brenna S. , Siebels B. , Voß H. , Seuring C. , Ferrer I. , Schlüter H. , Kneussel M. , Altmeppen HC. , Schweizer M. , Puig B. , Shafiq M. , Glatzel M.
Published: January 2024

Extracellular vesicles (EVs) have gained significant attention as pathology mediators and potential diagnostic tools for neurodegenerative diseases. However, isolation of brain-derived EVs (BDEVs) from tissue remains challenging, often involving enzymatic digestion steps that may compromise the integrity of EV proteins and overall functionality.

Here, we describe that collagenase digestion, commonly used for BDEV isolation, produces undesired protein cleavage of EV-associated proteins in brain tissue homogenates and cell-derived EVs. In order to avoid this effect, we studied the possibility of isolating BDEVs with a reduced amount of collagenase or without any protease. Characterization of the isolated BDEVs revealed their characteristic morphology and size distribution with both approaches. However, we revealed that even minor enzymatic digestion induces ‘artificial’ proteolytic processing in key BDEV markers, such as Flotillin-1, CD81, and the cellular prion protein (PrPC), whereas avoiding enzymatic treatment completely preserves their integrity. We found no differences in mRNA and protein content between non-enzymatically and enzymatically isolated BDEVs, suggesting that we are purifying the same BDEV populations with both approaches. Intriguingly, the lack of Golgi marker GM130 signal, often referred to as contamination contamination-negative marker in EV preparations, seems to result from enzymatic digestion rather than from its actual absence in BDEV samples.

Overall, we show that non-enzymatic isolation of EVs from brain tissue is possible and avoids artificial pruning of proteins while achieving a high BDEV yield and purity. This protocol will help to understand the functions of BDEV in a near-physiological setting, thus opening new research approaches.
The deubiquitylating enzyme Fat Facets promotes Fat signalling and restricts tissue growth
Authors: Dawson Lauren E. , Fulford Alexander D. , Sekar Aashika , Ribeiro Paulo S.
Published: January 2024

Tissue growth is regulated by many signals, including polarity cues. The Hippo signalling pathway restricts tissue growth and receives inputs from the planar cell polarity-controlling Fat signalling pathway. The atypical cadherin Fat restricts growth via several mechanisms that ultimately control the activity of the pro-growth transcriptional co-activator Yorkie. The Fat pathway modulates the activity of the Yorkie inhibitory kinase Warts, as well as the function of the FERM protein Expanded, which promotes Hippo signalling and also directly inhibits Yorkie. Although several Fat pathway activity modulators are known to be involved in ubiquitylation, the role of this post-translational modification in the pathway remains unclear. Moreover, no deubiquitylating enzymes have been described in this pathway. Here, using anin vivoRNAi screening approach, we identify the deubiquitylating enzyme Fat facets as a positive regulator of Fat signalling that is important for tissue growth control. Fat facets interacts genetically and physically with Fat signalling components and regulates transcription of Yorkie target genes. Thus, we uncover a role for reversible ubiquitylation in the control of Fat signalling and, by extension, in the regulation of tissue growth.
Development of the ECLIPSE model of meaningful outcome domains following lower limb amputation and prosthetic rehabilitation, through systematic review and best fit framework synthesis
Authors: Ostler Chantel , Dickinson Alex , Metcalf Cheryl , Donovan-Hall Margaret
Published: January 2024

Background

Little is known about which outcome domains characterise meaningful recovery following prosthetic rehabilitation and should be measured. Our previous qualitative work developed a conceptual model of outcome domains which are meaningful to patients. This qualitative synthesis aims to develop that model by exploring views and experiences of recovery captured in the limb loss literature, and use these to produce a second iteration of the model describing outcome domains of importance following prosthetic rehabilitation from the patient’s perspective.

Methods

Systematic searches were conducted using CINAHL, Psychinfo and Web of Science from 2011 to early 2023. Studies with a qualitative design focusing on views and experiences of lower limb prosthetic users were eligible for inclusion. Quality was assessed using the CASP tool. ‘Best Fit’ framework synthesis was used to synthesise the evidence and develop the conceptual model.

Results

40 studies were included, describing the experiences of 539 participants. Data supported the pre-existing conceptual model and led to development of four of the five domains. The newly named ECLIPSE model describes meaningful outcome domains as 1) Being able to participate in important activities and roles, 2) Participating in thewayI want to, 3) My prosthesis works for me, 4) If I am in pain, I can manage it, and 5) I am able to accept my new normal. Studies came from 15 countries showing good coverage of high-income settings. Few participants from low-and-middle-income countries were included, it is unclear if the ECLIPSE model describes outcome domains of importance in these settings.

Conclusions

This synthesis provides a rigorous foundation for understanding outcome domains of importance following lower limb prosthetic rehabilitation from the patient’s perspective. The ECLIPSE model is an accessible representation of recovery which could direct rehabilitation programmes, as well as inform the evaluation of prosthetic care through the selection of outcome measures.
The Two-dose MVA-BN Mpox Vaccine Induces a Nondurable and Low Avidity MPXV-specific Antibody Response
Authors: Oom Aaron L. , Wilson Kesi K. , Yonatan Miilani , Rettig Stephanie , Youn Heekoung Allison , Tuen Michael , Shah Yusra , DuMont Ashley L. , Belli Hayley M. , Zucker Jane R. , Rosen Jennifer B. , Herati Ramin Sedaghat , Samanovic Marie I. , Duerr Ralf , Kottkamp Angelica C. , Mulligan Mark J. ,   the NYC OSMI Study Group
Published: January 2024

The 2022 global outbreak of clade IIb mpox was the first major outbreak of mpox outside of African nations. To control the outbreak, public health officials began vaccination campaigns using the third-generation orthopoxvirus vaccine MVA-BN. Prior to this outbreak, the durability of MPXV-specific immunity induced by MVA-BN was poorly understood. In 2022, we launched the New York City Observational Study of Mpox Immunity (NYC OSMI,NCT05654883), a longitudinal study of 171 participants comprising MVA-BN vaccinees and mpox convalescent individuals. Peripheral blood sampling was performed at intervals including prior to vaccination, after one dose, and after the second dose. MVA-BN vaccinees with and without a history of smallpox vaccination demonstrated detectable mpox virus (MPXV)-specific memory B cells at one-year post-vaccination. Additionally, MVA-BN increased MPXV neutralizing titers in smallpox vaccine-naïve vaccinees, with a comparable peak titer reached in naïve and smallpox vaccine-experienced vaccinees. However, neutralizing titers returned to baseline within 5-7 months for naïve individuals, while remaining elevated in those with prior smallpox vaccination. Both naïve and experienced individuals generated robust, immunodominant IgG responses against MPXV H3 and A35, but naïve vaccinees’ IgG responses showed lower avidity than experienced vaccinees. These data highlight a low avidity antibody response elicited by MVA-BN that is short-lived in naïve vaccinees. This work supports the need for long-term studies on protection induced by MVA-BN including the potential need for booster doses as well as the development of next-generation orthopoxvirus vaccines.
Self-organizing glycolytic waves fuel cell migration and cancer progression
Authors: Zhan Huiwang , Pal Dhiman Sankar , Borleis Jane , Janetopoulos Chris , Huang Chuan-Hsiang , Devreotes Peter N.
Published: January 2024

Glycolysis has traditionally been thought to take place in the cytosol but we observed the enrichment of glycolytic enzymes in propagating waves of the cell cortex in human epithelial cells. These waves reflect excitable Ras/PI3K signal transduction and F-actin/actomyosin networks that drive cellular protrusions, suggesting that localized glycolysis at the cortex provides ATP for cell morphological events such as migration, phagocytosis, and cytokinesis. Perturbations that altered cortical waves caused corresponding changes in enzyme localization and ATP production whereas synthetic recruitment of glycolytic enzymes to the cell cortex enhanced cell spreading and motility. Interestingly, the cortical waves and ATP levels were positively correlated with the metastatic potential of cancer cells. The coordinated signal transduction, cytoskeletal, and glycolytic waves in cancer cells may explain their increased motility and their greater reliance on glycolysis, often referred to as the Warburg effect.
Opposing Sequential Biases in Direction and Time Reproduction: Influences of Task Relevance and Working Memory
Authors: Cheng Si , Chen Siyi , Shi Zhuanghua
Published: January 2024

Our current perception and decision-making are shaped by recent experiences, a phenomenon known as serial dependence. While serial dependence is well-documented in visual perception and has been recently explored in time perception, their functional similarities across non-temporal and temporal domains remain elusive, particularly in relation to task relevance and working memory load. To address this, we designed a unified experimental paradigm using coherent motion stimuli to test both direction and time reproduction. The direction and time tasks were randomly mixed across trials. Additionally, we introduced pre-cue versus post-cue settings in separate experiments to manipulate working memory load during the encoding phase. We found attractive biases in time reproduction but repulsive biases in direction estimation. Notably, the temporal attraction was more pronounced when the preceding task was also time-related. In contrast, the direction repulsion remained unaffected by the nature of the preceding task. Additionally, both attractive and repulsive biases were enhanced by the post-cue compared to the pre-cue. Our findings suggest that opposing sequential effects in non-temporal and temporal domains may originate from different processing stages linked to sensory adaptation and post-perceptual processes involving working memory.
Physical Activity, Sedentary Behavior and Microbiome: A Systematic Review and Meta-analysis
Authors: Pérez-Prieto Inmaculada , Plaza-Florido Abel , Ubago-Guisado Esther , Ortega Francisco B. , Altmäe Signe
Published: January 2024

Background

The effects of physical activity and sedentary behavior on human health are well known, however, the molecular mechanisms are poorly understood. Growing evidence points to physical activity as an important modulator of the microbial composition, while evidence of sedentary behavior is scarce. We aimed to synthesize and meta-analyze the current evidence about the effects of physical activity and sedentary behavior on microbiome across different body sites and in different populations.

Methods

A systematic search in PubMed, Web of Science, Scopus and Cochrane databases was conducted until September 2022. Random-effects meta-analyses including cross-sectional studies (activevs. inactive / athletesvs. non-athletes) or trials reporting the chronic effect of physical activity interventions on gut microbiome alpha-diversity in healthy individuals were performed.

Results

Ninety-one studies were included in this systematic review. Our meta-analyses of 2632 participants indicated no consistent effect of physical activity on microbial alpha-diversity, although there seems to be a trend toward a higher microbial richness in athletes compared to non-athletes. We observed an increase in short-chain fatty acids-producing bacteria such asAkkermansia,Faecalibacterium,VeillonellaorRoseburiain active individuals and after physical activity interventions.

Conclusions

Physical activity levels were positively associated with the relative abundance of short-chain fatty acids-producing bacteria. Athletes seem to have a richer microbiome compared to non-athletes. However, high heterogeneity between studies avoids to obtain conclusive information on the role of physical activity in microbial composition. Future multi-omics studies would enhance our understanding of the molecular effects of physical activity and sedentary behavior on the microbiome.
Polycomb Repressive Complex 1.1 Component, BCOR, Promotes Syncytiotrophoblast Differentiation in Mice and Humans
Authors: Sadowski Danielle , Corcoran Connie M. , Abdi Riyan , Zheng Teng , Okae Hiroaki , Arima Takahiro , Bardwell Vivian J. , Gearhart Micah D.
Published: January 2024

Early defects in placenta development are thought to underlie a range of adverse pregnancy conditions including miscarriage, fetal growth abnormalities, preeclampsia, and stillbirth. Differentiating trophoblast stem cells undergo a choreographed allocation of syncytiotrophoblast and extravillous trophoblast cells in response to signaling cues from the developing fetus and the uterine environment. The expression and activity of transcription factors and chromatin modifying enzymes change during differentiation to appropriately reshape the chromatin landscape in each cell type. We have previously found in mice that extraembryonic loss of BCOR, a conserved component of the epigenetic silencing complex Polycomb Repressive Complex 1.1 (PRC1.1), leads to a reduced labyrinth and expanded trophoblast giant cell population in the placenta. Molecular analysis of wild-type and BCOR loss-of-function male and female placentas by RNA-seq identified gene expression changes as early as E6.5. We found that BCOR is required to down regulate stem cell genes and repress factors that promote alternate lineages which leads to reduced levels of syncytiotrophoblasts. ChIP-seq experiments identified a number of directly bound functional targets includingPdgfaandWnt7b. In humans,BCORis mutated in X-linked syndromes involving fetal growth restriction and females with a heterozygous null mutation inBCORcan experience recurrent miscarriages. To establish a direct role forBCORin human placental development, we used CRISPR/Cas9 to knockoutBCORin male (CT29) and female (CT30) human trophoblast stem cells. Mutant cell lines retained capacity for induced differentiation into syncytiotrophoblast and extravillous trophoblasts and exhibited minimal changes in gene expression. However, in 3D cell culture using trophoblast organoid media,BCORknockout lines had significantly altered gene expression including homologs of stem cell genes upregulated inBcorknockout mice. CUT&RUN experiments in self-renewing and 3D cell culture identified genes directly bound by BCOR. Single cell profiling of wild type, knockout, and a P85L pathogenic knock-inBCORmutation showed a reduced capacity to differentiate into syncytiotrophoblasts after four days of differentiation. Together, these results suggest that BCOR is a conserved regulator of trophoblast development that represses stem cell genes during differentiation and maintains lineage fidelity by repressing genes that promote alternate cell fates.
The “No Phenotype” Challenge in Analyzing Mutant Mice
Authors: Papaioannou Virginia E. , Behringer Richard R.
Published: January 2024

If homozygous mutant mice survive to adulthood, are fertile, and have no visible phenotypes attributable to mutation of the relevant gene, there are a number of possible reasons why an effect of the mutation is not evident. Technical errors that might have occurred during gene targeting or genotyping must first be eliminated. Variable penetrance of the mutation should be considered as well as the possibility of age-related or late-onset phenotypes, such as tumor formation or other pathologies. The gene expression pattern and nature of the protein product of the gene could provide clues. A number of simple tests can be applied to uncover cryptic phenotypes that are not easily seen on casual inspection (e.g., tests of the senses and of balance and coordination). Genetic and environmental challenges can be applied to overtly normal mutant mice to reveal deviations from normal.
Hourglasslike spin excitation in a doped Mott insulator
Authors: Zhang Jia-Xin , Chen Chuan , Zhang Jian-Hao , Weng Zheng-Yu
Published: January 2024

We examine the dynamical magnetic response in a two-component resonating-valence-bond (RVB) description of the doped Mott insulator. The half-filled antiferromagnetic phase described by the Schwinger-boson mean-field theory will evolve into a bosonic-RVB state in the superconducting phase upon doping, where the doped holes introduce another fermionic itinerant spinon which forms a BCS-like RVB order. The spin excitations are thus composed of a resonance-like mode from the former and a weak dispersive mode from the itinerant component at the mean-field level. These two-component spinons are shown to give rise to an hourglasslike spin excitation at the random-phase approximation level via an antiferromagnetic coupling between the two modes, which provides an unconventional explanation of the experimental observations in the cuprate. In particular, we also discuss an instability towards an incommensurate magnetic order in this theoretical framework.

Published by the American Physical Society
2024
Thermodynamic bifurcations of boiling in solid-state nanopores
Authors: Paul Soumyadeep , Ito Yusuke , Hsu Wei-Lun , Daiguji Hirofumi
Published: January 2024

Boiling heat transfer is the basis of many commonly used cooling techniques. In cooling of electronic devices, for example, it is desirable to further miniaturize heat exchangers to achieve higher heat transfer, and thus it is necessary to understand boiling phenomena on shorter spatial and temporal scales. This is especially challenging at the nanometer scale because conventional imaging techniques cannot capture the dynamics of nanobubbles, owing to the Abbe diffraction limit. Here in this research, we utilize the nanopore Joule heating system that enables the generation of nanobubbles and simultaneous diagnosis of their nanosecond resolution dynamics using resistive pulse sensing. When a bias voltage is applied across a silicon nitride nanopore immersed in an aqueous salt solution, Joule heat is generated owing to the flow of ionic current. With increasing voltage, the Joule heating intensifies, and the temperature and entropy production in the pore increase. Our sensing results show that nanopore boiling follows the theory of minimum entropy production and attempts to settle to a minimum dissipative state. This results in two boiling bifurcations corresponding to the transition between different boiling states. These characteristics of nanopore boiling are represented by an -shaped boiling curve, experimentally obtained from the Joule heat variation with the applied voltage. A theoretical framework is proposed to model the thermodynamics of nanopore bubbles and estimates the system dissipation, which explains the four arms of the -shaped boiling curve. The present study reveals that the utilization of nanopore boiling as a benchmark platform offers a valuable means for investigating the intricate boiling phenomenon and its correlation with nanoscale bubble dynamics. This would provide much-needed fundamental insights into the chaotic transition boiling regime, which is least understood.

Published by the American Physical Society
2024
Reciprocal microswimming in fluctuating and confined environments
Authors: Hiruta Yoshiki , Ishimoto Kenta
Published: January 2024

From bacteria and sperm cells to artificial microrobots, self-propelled microscopic objects at low Reynolds numbers often perceive fluctuating mechanical and chemical stimuli and contact exterior wall boundaries both in nature and the laboratory. In this paper, we theoretically investigate the fundamental features of microswimmers by focusing on their reciprocal deformation. Although the scallop theorem prohibits the net locomotion of reciprocal microswimmers, by analyzing a two-sphere swimmer model, we show that in a fluctuating and geometrically confined environment, reciprocal deformations can afford a statistically average displacement. After designing the shape gait, a reciprocal swimmer can migrate in any direction, even in the statistical sense, while the statistical average of passive rigid particles statistically diffuses in a particular direction in the presence of external boundaries. To elucidate this symmetry breakdown, by introducing an impulse response function, we derive a general formula for predicting the nonzero net displacement of a reciprocal swimmer. Using this theory, we determine the relation between the shape gait and net locomotion as well as the net diffusion constant increase and decrease, owing to a reciprocal deformation. Based on these findings and a theoretical formulation, we provide a fundamental basis for environment-coupled statistical locomotion. Thus, this paper is valuable for understanding biophysical phenomena in fluctuating environments, designing artificial microrobots, and conducting laboratory experiments.

Published by the American Physical Society
2024
Dynamic, technological and marketing capabilities in MSMEs’ recovery from COVID-19 – the moderating role of organizational learning
Authors: Prayag Girish , Chowdhury Mesbahuddin , Ozanne Lucie K.
Published: January 2024

Purpose

Using dynamic capabilities (DCs) theory, the authors assess whether micro, small and medium-sized enterprises (MSMEs) can leverage DCs to improve operational capabilities (OCs) during the COVID-19 pandemic. The authors also identify whether organizational learning (OL) affects the relationship between DCs and OCs.

Design/methodology/approach

The authors test these propositions on a sample of 419 MSMEs from Australia and New Zealand.

Findings

DCs have no direct effect on OCs, technological or marketing capabilities (TCs or MCs). OL moderates the effect of DCs on both TCs and MCs.

Research limitations/implications

The study assesses only MCs and TCs as OCs and does not explicitly measure pandemic impacts on organizations. However, the results illustrate the importance of OL during crises for recovery purposes.

Practical implications

Managers can use the findings to improve structure, processes and knowledge management emanating from MCs and TCs within organizations impacted by the COVID-19 pandemic.

Originality/value

The authors use a multi-dimensional measure of OL and show that during the pandemic, OL is a critical factor that allows organizations to transform the benefits conferred by DCs into MCs and TCs.
The effects of different billboard advertisement language on TV sports audiences’ recognition, recall and search intention of the sponsor signage
Authors: Xu Ziyuan , Cao Yuanyuan , Matsuoka Hirotaka
Published: January 2024

Purpose

The impact of various factors on how TV sports audiences perceive sport event sponsors’ billboards around sports facilities has been the subject of extensive research. Despite numerous factors that impact the effectiveness of sponsor signage at sporting events, there has been a lack of research regarding the language used for such signage around sports facilities’ billboards. Therefore, this study aims to investigate the effects of billboard advertisement language on TV sports audiences’ recognition, recall and search intention to sponsor signage.

Design/methodology/approach

This study employed an online experimental design. Participants (n = 925) were recruited from two linguistically different regions: Chinese and English. Participants were randomly assigned to one of two conditions: watching tennis video matches with billboard advertisements presented in either the Roman alphabet exclusively or in a combination of the Roman alphabet and Chinese characters.

Findings

This study revealed that although language cannot significantly impact audiences’ unaided recall of a brand, it does have a discernible effect on brand recognition and search intention among audiences. Additionally, people are more likely to search for brands in their native language. Participants from various regions tend to have different recognition rates and search intentions for sport sponsors.

Originality/value

This is the first manuscript examining the use of different languages in relation to audiences’ recognition and recall of sports sponsorship. It provides empirical evidence of the importance of carefully considering the language used in sponsor signage around stadium billboards to optimize the efficacy of sponsorships at sports events.