bluuebunny/crossref_metadata_2025 huggingface dataset:
On the brain struggles to recognize basic facial emotions with face masks: an fMRI study
Authors: Abutalebi Jubin , Gallo Federico , Fedeli Davide , Houdayer Elise , Zangrillo Federica , Emedoli Daniele , Spina Alfio , Bellini Camilla , Del Maschio Nicola , Iannaccone Sandro , Alemanno Federica
Published: January 2024

Introduction

The COVID-19 pandemic impacted public health and our lifestyles, leading to new social adaptations such as quarantine, social distancing, and facial masks. Face masks, covering extended facial zones, hamper our ability to extract relevant socio-emotional information from others’ faces. In this fMRI study, we investigated how face masks interfere with facial emotion recognition, focusing on brain responses and connectivity patterns as a function of the presence of a face mask.

Methods

A total of 25 healthy participants (13F; mean age: 32.64 ± 7.24y; mean education: 18.28 ± 1.31y) were included. Participants underwent task-related fMRI during the presentation of images of faces expressing basic emotions (joy or fear versus neutral expression). Half of the faces were covered by a face mask. Subjects had to recognize the facial emotion (masked or unmasked). FMRI whole-brain and regions-of-interest analyses were performed, as well as psychophysiological interaction analysis (PPI).

Results

Subjects recognized better and faster emotions on unmasked faces. FMRI analyses showed that masked faces induced a stronger activation of a right occipito-temporal cluster, including the fusiform gyrus and the occipital face area bilaterally. The same activation pattern was found for the neutral masked > neutral unmasked contrast. PPI analyses of the masked > unmasked contrast showed, in the right occipital face area, a stronger correlation with the left superior frontal gyrus, left precentral gyrus, left superior parietal lobe, and the right supramarginal gyrus.

Discussion

Our study showed how our brain differentially struggles to recognize face-masked basic emotions, implementing more neural resources to correctly categorize those incomplete facial expressions.
Productive art engagement in a hybrid format: effects on emotions of older adults during COVID-19 pandemic
Authors: Payne Magali , Galery Kevin , Plonka Alexandra , Lemaire Justine , Derreumaux Alexandre , Fabre Roxane , Mouton Aurélie , Sacco Guillaume , Guerin Olivier , Manera Valeria , Robert Philippe , Beauchet Olivier , Gros Auriane
Published: January 2024

Introduction

Previous studies have shown benefits of productive art-activity on frail older adults' mental and physical health. In this study, we investigated the effects of art-producing activities in a hybrid format (in-person and online) in a context of lockdown compared with previous studies taking place in museums and their effects on wellbeing, quality of life, physical frailty, and apathy in older adults.

Methods

We conducted a randomized unicentric control trial on a sample of 126 seniors older than 65 years (mean age 71.9 ± 2.3, 81% women) living in Nice (France). Participants were randomized in two parallel groups (intervention group with n = 62 vs. control group with n = 64) conducted during pandemic, between March and May 2021. The intervention group involved participatory art-based activities conducted in a hybrid format, either in-person or online, once a week for 2 h over a 12-week period. No specific intervention was proposed to the control group. The main aim was to evaluate how this hybrid format would impact the wellbeing, quality of life, and physical frailty of participants. The secondary aim was to compare our results with the previous studies conducted by Beauchet et al., and the third aim was to evaluate the impact of the intervention on apathy. Validated scales were implemented in RedCap and administered at baseline (M0) and at the end of the third month (M3).

Results

The intervention group showed significant improvement in their quality of life (p = 0.017) and their level of apathy (p = 0.016) after intervention. Emotional blunting increased significantly in the control group (p = 0.016) while it remained stable in the intervention group. No significant improvement was observed on the frailty, and wellbeing scores remained constant in both groups.

Conclusion

This randomized control trial confirmed emotional effects on seniors practicing an art-based activity in a hybrid format during pandemic on a weekly basis for 3 months.

Clinical Trial Registration

ClinicalTrials.gov, identifier: NCT04570813.
The acute effects of pre- and mid-exercise carbohydrate ingestion on the immunoregulatory stress hormone release in experienced endurance athletes—a systematic review
Authors: Christ Tabea , Ringleb Miriam , Haunhorst Simon , Fennen Lena , Jordan Paul M. , Wagner Heiko , Puta Christian
Published: January 2024

Background

In times of physical stress, the body orchestrates a multisystemic regulatory response. The hormones epinephrine and norepinephrine play a role in the immediate regulation chain, while cortisol is involved in delayed regulation. The release of those stress hormones in response to exercise has previously been reported to elicit diverse immune reactions.

Objective

The aim of this systematic review was to examine and present the acute effects of immediate pre- and mid-exercise carbohydrate ingestion on cortisol, epinephrine and norepinephrine levels in experienced endurance athletes.

Methods

A systematic literature search was conducted using PubMed, Cochrane Library and Web of Science in accordance with PRISMA guidelines up to February 2023. Randomized controlled trials in English or German language were included if baseline and at least two follow-up measures of blood plasma or serum of chosen stress hormones (cortisol, epinephrine, norepinephrine) were collected in response to prolonged continuous endurance activity. Eligibility furthermore required an acute carbohydrate ingestion of at least 30 g of carbohydrates per hour no more than 30 min before start of the exercise, as well as a placebo-controlled study design.

Results

Eleven studies of moderate to high quality were included in this review. Carbohydrate ingestion of at least 30 g per hour was able to attenuate rises in cortisol concentration in majority of the included studies. Epinephrine levels were considerably lower with ingestion of carbohydrates compared to placebo in all studies. Norepinephrine concentrations were largely unaffected by acute carbohydrate feeding.

Conclusion

Pre- and mid-exercise ingestion of carbohydrates seems an effective dietary strategy to attenuate rises in cortisol and epinephrine levels and, thus, an effective countermeasure for endurance exercise-induced increases in stress hormone levels.
Systems Connected to Inequities in Access to Kidney Transplantation and the Value of Intersectionality
Authors: Nonterah Camilla W.
Published: January 2024

Patients from minoritized backgrounds based on race/ethnicity, gender, sexuality, and other social identities are more likely to experience inequities in access in kidney transplantation. Although these inequities have been reported over the decades, limited research focuses on the experiences of patients with intersecting minoritized social statuses and the mechanisms that contribute to their reduced access to transplantation. Intersectionality, a framework for understanding the ways in which multiple social identities represent interacting systems of oppression and privilege, offers a nuanced approach for understanding the experiences of patients diagnosed with end-stage organ disease with intersecting social identities. This article outlines complex systems that perpetuate inequities by highlighting the value of intersectionality in studying disparate outcomes to transplant and providing recommendations for the transplant community. This article aligns with the ESOT call for action to promote equity in transplantation worldwide.
Hungarian Representative Exhibitions and the Rhetoric of Display in the 1920s
Authors: Albert Samuel D.
Published: January 2024

This article examines the series of art exhibitions organized by the Hungarian government in the 1920s. After examining the bureaucratic framework of the exhibition, the article then discusses the materials displayed at five different exhibitions, organized between 1920 and 1927. While much of the material displayed remained the same, the rhetoric, particularly the catalog essays that accompanied the exhibition provided insight into the organizers’ goals and the governmental ideology underlying that rhetoric.
Diagnostic Performance of a Novel Ultra-Thin Endoscopy under Narrow-Band Imaging for Superficial Squamous Cell Carcinoma of the Pharynx and Esophagus
Authors: Dobashi Akira , Hara Yuko , Furuhashi Hiroto , Matsui Hiroaki , Tada Naoya , Ito Mamoru , Futakuchi Toshiki , Kobayashi Masakuni , Ono Shingo , Aizawa Daisuke , Yamauchi Takashi , Suka Machi , Sumiyama Kazuki
Published: January 2024

This study aimed to evaluate the diagnostic utility of the ultra-thin endoscope (UTE) for superficial squamous cell carcinoma (SSCC) compared to magnifying endoscopy (ME) under narrow-band imaging. Participants underwent endoscopic examination, and images of pharyngeal and esophageal SCCs, as along with suspicious SSCC lesions, were collected using UTE and ME on the same day. Three image catalogs (UTE, ME-1, and ME-2) were created and reviewed by three expert endoscopists. ME-1 and ME-2 contained the same endoscopic images. The primary endpoint was the intra-observer agreement for diagnosing SCC. Eighty-six lesions (SCC = thirty-nine, non-SCC = forty-seven) in 43 participants were identified. The kappa values for the intra-observer agreement between UTE and ME-1 vs. the control (ME-1 vs. ME-2) were 0.74 vs. 0.84, 0.63 vs. 0.76, and 0.79 vs. 0.88, respectively. The accuracies for diagnosing SCC by UTE and ME-1 were 87.2% vs. 86.0%, 78.0% vs. 73,2%, and 75.6 vs. 82.6%, respectively, with no significant differences (p > 0.05). The rates of lesions that were diagnosed with confidence by UTE and ME-1 were 30.2% vs. 27.9%, 55.8% vs. 62.8%, and 58.1% vs. 55.8%, respectively. UTE demonstrates substantial diagnostic performance for SSCC in the pharynx and esophagus.
Circulating Adipocytokines and Insulin Like-Growth Factors and Their Modulation in Obesity-Associated Endometrial Cancer
Authors: Ray Irene , Möller-Levet Carla S. , Michael Agnieszka , Butler-Manuel Simon , Chatterjee Jayanta , Tailor Anil , Ellis Patricia E. , Meira Lisiane B.
Published: January 2024

The rising global incidence of uterine cancer is linked to the escalating prevalence of obesity. Obesity results in alterations in adipocytokines and IGFs, driving cancer progression via inflammation, increased cell proliferation, and apoptosis inhibition, although the precise mechanisms are still unclear. This study examined a set of six markers, namely, adiponectin, leptin, IL6, TNFα, IGF1, and IGF2 and compared them between fifty age-matched endometrial cancer patients (study group) and non-cancer patients with benign gynaecological conditions (control group). We also assessed the relationship of these markers with obesity and explored the correlation between these markers and various tumour characteristics. In the cancer population, these markers were also assessed 24 h and 6 months post-surgery. Remarkably, low adiponectin levels were associated with a 35.8% increase in endometrial cancer risk. Interestingly, compared to control subjects where IGF levels decreased after menopause, post-menopausal women in the study group showed elevated IGF1 and IGF2 levels, suggesting a potential influence of endometrial cancer on the IGF system, particularly after menopause. Lastly, it is noteworthy that a discernible inverse relationship trend was observed in the levels of adipocytokines and IGFs 6 months post-surgery. This indicates that treatment for endometrial cancer may have a differential impact on adipocytokines and IGFs, potentially holding clinical significance that merits further investigation.
Stochastic Thermodynamics of Learning Parametric Probabilistic Models
Authors: Parsi Shervin S.
Published: January 2024

We have formulated a family of machine learning problems as the time evolution of parametric probabilistic models (PPMs), inherently rendering a thermodynamic process. Our primary motivation is to leverage the rich toolbox of thermodynamics of information to assess the information-theoretic content of learning a probabilistic model. We first introduce two information-theoretic metrics, memorized information (M-info) and learned information (L-info), which trace the flow of information during the learning process of PPMs. Then, we demonstrate that the accumulation of L-info during the learning process is associated with entropy production, and the parameters serve as a heat reservoir in this process, capturing learned information in the form of M-info.
Stochastic Antiresonance for Systems with Multiplicative Noise and Sector-Type Nonlinearities
Authors: Stoica Adrian-Mihail , Yaesh Isaac
Published: January 2024

The paradigm of stochastic antiresonance is considered for a class of nonlinear systems with sector bounded nonlinearities. Such systems arise in a variety of situations such as in engineering applications, in physics, in biology, and in systems with more general nonlinearities, approximated by a wide neural network of a single hidden layer, such as the error equation of Hopfield networks with respect to equilibria or visuo-motor tasks. It is shown that driving such systems with a certain amount of state-multiplicative noise, one can stabilize noise-free unstable systems. Linear-Matrix-Inequality-based stabilization conditions are derived, utilizing a novel non-quadratic Lyapunov functional and a numerical example where state-multiplicative noise stabilizes a nonlinear system exhibiting chaotic behavior is demonstrated.
Study on the Spatiotemporal Evolution and Influencing Factors of Forest Coverage Rate (FCR): A Case Study on Yunnan Province Based on Remote Sensing Image Interpretation
Authors: Yang Renyi , He Yimei , Zhong Changbiao , Yang Zisheng , Wang Xian , Xu Mingjun , Cao Linlin
Published: January 2024

The study of the forest coverage rate (FCR) is related to the ecological environment and sustainable development goals (SDGs) of a region. In light of the lack of an organic integration method of “spatiotemporal evolution, correlation analysis, and change prediction” and the lack of a methodology that integrates methods of “remote sensing (RS) and GIS, multi-phase LUCC, and construction of econometric models” in the research methods at present, this study focus on Yunnan, a typical border province located in China with a relatively fragile “innate” ecological environment, as the research area. Based on the interpretation of land use/land cover (LULC) data retrieved from seven periods RS images (1990, 1995, 2000, 2005, 2010, 2015, and 2020), the spatiotemporal evolution of FCR in 129 counties was analyzed. Complementary research methods, such as the spatial econometric model, geographically weighted regression (GWR), and the geographic detector (GD), are used to reveal the influencing factors of FCR. Finally, this study predicts the FCRs of 129 counties in Yunnan from 2025 to 2050. The FCR in Yunnan presents an increasing trend year by year, increasing from 28.96% in 1990 to 49.05% in 2020. In addition, it exhibits spatial agglomeration characteristics with fewer values in the east and more in the west. The analysis of influencing factors show that the increases in the per capita GDP, land utilization rate, and annual average temperature, and the implementation of the Conversion of Cultivated Land into Forest Project (CCFP) will significantly improve the FCR, while the increases in the population density land reclamation rate, the proportion of construction land area, and the proportion of soil erosion land area will significantly reduce the FCR. Furthermore, the FCR is influenced by multiple factors, and the relative factors observed not only show significant spatial differences, but also present complex and diverse patterns, with the additional characteristics of being interwoven and overlapping. This study contributes to expanding and improving the methods and pathways of exploring the spatiotemporal evolution characteristics of FCR in ecologically fragile areas using RS methods, providing a reference for increasing FCR and improving the ecological environment’s quality in Yunnan Province and other ecologically fragile areas.
Migration of Nutrient Substances and Characteristic Changes of Chicken White Soup Emulsion from Chicken Skeleton during Cooking
Authors: Guan Haining , Tian Yanli , Feng Chunmei , Leng Siqi , Zhao Shifa , Liu Dengyong , Diao Xiaoqin
Published: January 2024

The protein and fat in chicken skeleton can be emulsified in a boiling state to form milky white chicken soup. White chicken soup has a delicious taste, good nutritional value, a beautiful color, and volatile flavor compounds. However, cooking time significantly impacts the quality of white chicken soup. Herein, we investigated the influence of cooking time (30, 60, 90, 120, 150, 180, and 210 min) on the migration of nutrient substances and characteristics changes in white chicken soup from chicken skeletons. The results showed that nutrients such as total lipids, water-soluble protein, total sugars, solid matter, and oligopeptides in the chicken skeletons’ tissue continuously migrated into the soup during the cooking process. The total nutrient content in the chicken soup was highest after cooking for 180 min. Simultaneously, the white chicken soup obtained after cooking for 180 min had low interfacial tension and high whiteness, viscosity, and storage stability. The high stability index was associated with increased ζ potential and decreased particle size. The contact angle analysis results also indicated that the stability of the white chicken soup was improved when the cooking time reached 180 min. This research provides basic information for the production of high-quality white chicken soup.
Health-Related Quality of Life among Older Adults with Dementia Living in Vietnamese Nursing Homes
Authors: Nguyen Thanh Xuan , Nguyen Anh Huynh Phuong , Nguyen Huong Thi Thu , Nguyen Thu Thi Hoai , Nguyen Hoa Lan , Goldberg Robert Joel , Thillainadesan Janani , Naganathan Vasi , Vu Huyen Thi Thanh , Tran Luc Viet , Nguyen Anh Trung
Published: January 2024

Better understanding of the quality of life among nursing home residents with dementia is important for developing interventions. The objectives of this cross-sectional study were to examine factors associated with poor health-related quality of life in older people with dementia living in nursing homes in Hanoi, Vietnam. In-person interviews were conducted with 140 adults who were 60 years and older with dementia, and information about their quality of life was obtained using the Quality of Life in Alzheimer’s Disease (QOL-AD) scale. The sociodemographic and clinical factors associated with poor health-related quality of life (lowest quartile) were assessed through the results of physical tests, interviews with nursing home staff, and review of medical records. The average age of the study sample was 78.3 years, 65% were women, and their average QOL-AD total score was 27.3 (SD = 4.4). Malnutrition, total dependence in activities of daily living, and urinary incontinence were associated with poor quality of life after controlling for multiple potentially confounding factors. Our findings show that Vietnamese nursing home residents with dementia have a moderate total quality of life score, and interventions based on comprehensive geriatric assessment remain needed to modify risk factors related to poor health-related quality of life.
Mapping Access to Children’s Hospitals in Texas
Authors: Maleki Shadi , Dede-Bamfo Nathaniel , Ekren Elizabeth , Mohammadalizadehkorde Milad , Villagran Melinda
Published: January 2024

Vehicle access, travel time, and distance to hospitals and emergency rooms with sufficient patient beds are critical healthcare accessibility measures, especially for children who require specific pediatric services. In a large state like Texas with vast rural areas and limited public transit infrastructure, 75% of the children live over an hour from the closest facility that provides pediatric emergency services or specialty care. In view of this challenge, this study first sought to map the prevailing geographical accessibility to children’s hospitals and, second, to model the hospital beds per capita for each hospital’s service area within the state of Texas. The results showed disparities in accessing emergency pediatric care, especially in rural areas. However, despite major metro areas recording better geographical accessibility to pediatric healthcare, residents in these areas may experience limited hospital bed availability. The findings indicate an urgent need for more pediatric healthcare services in rural Texas. Given the increasing population growth in metro areas and their surroundings, there is also a need for the expansion of healthcare infrastructure in these areas.
“A Huge Gap”: Health Care Provider Perspectives on Cancer Screening for Aboriginal and Torres Strait Islander People in the Northern Territory
Authors: Taylor Emma V. , Dugdale Sarah , Connors Christine M. , Garvey Gail , Thompson Sandra C.
Published: January 2024

Cancer is one of the leading causes of death for Aboriginal and Torres Strait Islander people in the Northern Territory (NT). Accessible and culturally appropriate cancer screening programs are a vital component in reducing the burden of cancer. Primary health care plays a pivotal role in facilitating the uptake of cancer screening in the NT, due to the significant challenges caused by large distances, limited resources, and cultural differences. This paper analyses health care provider perspectives and approaches to the provision of cancer screening to Aboriginal people in the NT that were collected as part of a larger study. Semi-structured interviews were conducted with 50 staff from 15 health services, including 8 regional, remote, and very remote primary health care (PHC) clinics, 3 hospitals, a cancer centre, and 3 cancer support services. Transcripts were thematically analysed. Cancer screening by remote and very remote PHC clinics in the NT is variable, with some staff seeing cancer screening as a “huge gap”, while others see it as lower priority compared to other conditions due to a lack of resourcing and the overwhelming burden of acute and chronic disease. Conversely, some clinics see screening as an area where they are performing well, with systematic screening, targeted programs, and high screening rates. There was a large variation in perceptions of the breast screening and cervical screening programs. However, participants universally reported that the bowel screening kit was complicated and not culturally appropriate for their Aboriginal patients, which led to low uptake. System-level improvements are required, including increased funding and resourcing for screening programs, and for PHC clinics in the NT. Being appropriately resourced would assist PHC clinics to incorporate a greater emphasis on cancer screening into adult health checks and would support PHCs to work with local communities to co-design targeted cancer screening programs and culturally relevant education activities. Addressing these issues are vital for NT PHC clinics to address the existing cancer screening gaps and achieving the Australian Government pledge to be the first nation in the world to eliminate cervical cancer as a public health problem by 2035. The implementation of the National Lung Cancer Screening Program in 2025 also presents an opportunity to deliver greater benefits to Aboriginal communities and reduce the cancer burden.
Cognitive Job Demands and Sports Participation among Young Workers: What Moderates the Relationship?
Authors: Wiertsema Sara , Kraaykamp Gerbert , Beckers Debby
Published: January 2024

Cognitive job demands are theoretically and empirically associated with sports participation in various ways. Workers may be overwhelmed by stress and fatigue from their workload and therefore refrain from sports activities, but they can also feel the need to use sports as a way to recover and detach from work. The strategy to which workers adhere can depend on workers’ resources that moderate the cognitive job demands and sports participation relationship, such as educational attainment, being a parent, or having worktime and work location control. To test our expectations, we used recent information on sports participation by young working adults from the Netherlands (N = 2032). Using multinomial logistic regression modelling, we found that workers in mentally demanding jobs were more likely to participate in sports more than three times a week. In particular, workers without children reported a higher likelihood of participating in sports more than three times a week when they experienced high cognitive job demands. Among the higher-educated, workers with high cognitive job demands were less likely to participate in sports one to three times a week. We reflect on the academic and policy-related implications of our findings.
Analyzing Multiple Social Determinants of Health Using Different Clustering Methods
Authors: Zhang Li , Clay Olivio J. , Lee Seung-Yup , Howell Carrie R.
Published: January 2024

Social determinants of health (SDoH) have become an increasingly important area to acknowledge and address in healthcare; however, dealing with these measures in outcomes research can be challenging due to the inherent collinearity of these factors. Here we discuss our experience utilizing three statistical methods—exploratory factor analysis (FA), hierarchical clustering, and latent class analysis (LCA)—to analyze data collected using an electronic medical record social risk screener called Protocol for Responding to and Assessing Patient Assets, Risks, and Experience (PRAPARE). The PRAPARE tool is a standardized instrument designed to collect patient-reported data on SDoH factors, such as income, education, housing, and access to care. A total of 2380 patients had complete PRAPARE and neighborhood-level data for analysis. We identified a total of three composite SDoH clusters using FA, along with four clusters identified through hierarchical clustering, and four latent classes of patients using LCA. Our results highlight how different approaches can be used to handle SDoH, as well as how to select a method based on the intended outcome of the researcher. Additionally, our study shows the usefulness of employing multiple statistical methods to analyze complex SDoH gathered using social risk screeners such as the PRAPARE tool.
Placental Transfer Efficiency of Neutralizing Antibodies on SARS-CoV-2 Vaccination before and after Pregnancy in Mexican Women
Authors: Martínez-Quezada Rebeca , Miguel-Rodríguez Carlos Emilio , Ramírez-Lozada Tito , Valencia-Ledezma Omar Esteban , Acosta-Altamirano Gustavo
Published: January 2024

The protection of the neonate against pathogens depends largely on the antibodies transferred placentally from the mother; for this reason, maternal vaccination against emerging viruses, such as SARS-CoV-2, is of vital importance. Knowing some of the immunogenic factors that could alter the placental transfer of antibodies could aid in understanding the immune response and neonatal protection after maternal vaccination. In this study, we analyzed the efficiency of the placental transfer of binding and neutralizing antibodies, as well as some factors that could alter the passive immune response, such as the trimester of gestation at the time of immunization, the number of doses received by the mother and the type of vaccine. Binding IgG antibodies were detected by ELISA, and the detection of neutralizing antibodies was carried out using flow cytometry. Our results show efficient transfer rates (>1), which are higher when maternal vaccination occurs during the third trimester of gestation. Antibodies are detectable in mothers and their neonates after 12 months of maternal immunization, suggesting than the vaccination against COVID-19 before and during pregnancy in the Mexican population induces a lasting neutralizing response in mothers and their newborns.
Networked Cluster Formation via Trigonal Lipid Modules for Augmented Ex Vivo NK Cell Priming
Authors: Park Jaewon , Kim Sungjun , Jangid Ashok Kumar , Park Hee Won , Kim Kyobum
Published: January 2024

Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol (PEG) material to assemble NK cell clusters via multiple hydrophobic lipid insertions into cellular membranes. Our lipid conjugate-mediated ex vivo NK cell priming sufficiently augmented the structural modulation of clusters, facilitated diffusional signal exchanges, and finally activated NK cell population with the clusters. Without any inhibition in diffusional signal exchanges and intrinsic proliferative efficacy of NK cells, effectively prime NK cell clusters produced increased interferon-gamma, especially in the early culture periods. In conclusion, the present study demonstrates that our novel lipid conjugates could serve as a promising alternative for future NK cell mass production.
HTRA2/OMI-Mediated Mitochondrial Quality Control Alters Macrophage Polarization Affecting Systemic Chronic Inflammation
Authors: Liu Qingqing , Yan Xiaoyu , Yuan Yuan , Li Runyuan , Zhao Yuanxin , Fu Jiaying , Wang Jian , Su Jing
Published: January 2024

Systemic chronic inflammation (SCI) due to intrinsic immune over-activation is an important factor in the development of many noninfectious chronic diseases, such as neurodegenerative diseases and diabetes mellitus. Among these immune responses, macrophages are extensively involved in the regulation of inflammatory responses by virtue of their polarization plasticity; thus, dysregulation of macrophage polarization direction is one of the potential causes of the generation and maintenance of SCI. High-temperature demand protein A2 (HtrA2/Omi) is an important regulator of mitochondrial quality control, not only participating in the degradation of mis-accumulated proteins in the mitochondrial unfolded protein response (UPRmt) to maintain normal mitochondrial function through its enzymatic activity, but also participating in the regulation of mitochondrial dynamics-related protein interactions to maintain mitochondrial morphology. Recent studies have also reported the involvement of HtrA2/Omi as a novel inflammatory mediator in the regulation of the inflammatory response. HtrA2/Omi regulates the inflammatory response in BMDM by controlling TRAF2 stabilization in a collagen-induced arthritis mouse model; the lack of HtrA2 ameliorates pro-inflammatory cytokine expression in macrophages. In this review, we summarize the mechanisms by which HtrA2/Omi proteins are involved in macrophage polarization remodeling by influencing macrophage energy metabolism reprogramming through the regulation of inflammatory signaling pathways and mitochondrial quality control, elucidating the roles played by HtrA2/Omi proteins in inflammatory responses. In conclusion, interfering with HtrA2/Omi may become an important entry point for regulating macrophage polarization, providing new research space for developing HtrA2/Omi-based therapies for SCI.
Organelle Genomes of Epipogium roseum Provide Insight into the Evolution of Mycoheterotrophic Orchids
Authors: Zhao Zhuang , Li Yuanyuan , Zhai Jun-Wen , Liu Zhong-Jian , Li Ming-He
Published: January 2024

Epipogium roseum, commonly known as one of the ghost orchids due to its rarity and almost transparent color, is a non-photosynthetic and fully mycoheterotrophic plant. Given its special nutritional strategies and evolutionary significance, the mitogenome was first characterized, and three plastomes sampled from Asia were assembled. The plastomes were found to be the smallest among Orchidaceae, with lengths ranging from 18,339 to 19,047 bp, and exhibited high sequence variety. For the mitogenome, a total of 414,552 bp in length, comprising 26 circular chromosomes, were identified. A total of 54 genes, including 38 protein-coding genes, 13 tRNA genes, and 3 rRNA genes, were annotated. Multiple repeat sequences spanning a length of 203,423 bp (45.47%) were discovered. Intriguingly, six plastid regions via intracellular gene transfer and four plastid regions via horizontal gene transfer to the mitogenome were observed. The phylogenomics, incorporating 90 plastomes and 56 mitogenomes, consistently revealed the sister relationship of Epipogium and Gastrodia, with a bootstrap percentage of 100%. These findings shed light on the organelle evolution of Orchidaceae and non-photosynthetic plants.
PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer
Authors: Cassalia Fortunato , Danese Andrea , Tudurachi Ina , Federico Serena , Zambello Anna , Guidotti Alessia , Franceschin Ludovica , Bolzon Anna , Naldi Luigi , Belloni Fortina Anna
Published: January 2024

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.
Delving into the Role of lncRNAs in Papillary Thyroid Cancer: Upregulation of LINC00887 Promotes Cell Proliferation, Growth and Invasion
Authors: Tous Cristina , Muñoz-Redondo Carmen , Gavilán Angela , Bravo-Gil Nereida , Baco-Antón Fátima , Navarro-González Elena , Antiñolo Guillermo , Borrego Salud
Published: January 2024

Papillary thyroid carcinoma (PTC) is the most common histological category of thyroid cancer. In recent years, there has been an increasing number of studies on lncRNAs in PTC. Long intergenic non-protein coding RNA 887 (LINC00887) is a critical oncogene in developing other cancers. LINC00887 is upregulated in PTC samples but its role in PTC is currently unclear. This study aimed to investigate the impact the disruption of LINC00887 expression has on PTC progression. We performed a CRISPR/Cas9 strategy for the truncation of LINC00887 in BCPAP and TPC1 cell lines. Functional assays showed that LINC00887 knockdown in both TPC1 and BCPAP cells reduced cell proliferation, colony formation and migration, delayed the cell cycle, and increased apoptosis. These results strengthened the role of LINC00887 in cancer and showed for the first time that this lncRNA could be a potential oncogene in PTC, acting as a tumor promoter. Modulation of the immune system may be one of the etiopathogenic mechanisms of LINC00887 in PTC, as shown by the observed influence of this lncRNA on PD-L1 expression. In addition, the biological pathways of LINC00887 identified to date, such as EMT, the Wnt/β-catenin signaling pathway or the FRMD6-Hippo signaling pathway may also be relevant regulatory mechanisms operating in PTC.
Treatment of Double-Refractory Chronic Lymphocytic Leukemia—An Unmet Clinical Need
Authors: Zygmunciak Przemysław , Robak Tadeusz , Puła Bartosz
Published: January 2024

Recent years have seen significant improvement in chronic lymphocytic leukemia (CLL) management. Targeting B-cell lymphoma (BCL-2) and Bruton’s kinase (BTK) have become the main strategies to restrain CLL activity. These agents are generally well tolerated, but the discontinuation of these therapies happens due to resistance, adverse effects, and Richter’s transformation. A growing population of patients who have previously used both BTK inhibitors and BCL2 suffer from the constriction of the following regimens. This review explores the resistance mechanisms for both ibrutinib and venetoclax. Moreover, we present innovative approaches evaluated for treating double-refractory CLL.
Re-Engineering Therapeutic Anti-Aβ Monoclonal Antibody to Target Amyloid Light Chain
Authors: Bai Jingyi , Li Xi , Zhao Jun , Zong Huifang , Yuan Yuan , Wang Lei , Zhang Xiaoshuai , Ke Yong , Han Lei , Xu Jianrong , Ma Buyong , Zhang Baohong , Zhu Jianwei
Published: January 2024

Amyloidosis involves the deposition of misfolded proteins. Even though it is caused by different pathogenic mechanisms, in aggregate, it shares similar features. Here, we tested and confirmed a hypothesis that an amyloid antibody can be engineered by a few mutations to target a different species. Amyloid light chain (AL) and β-amyloid peptide (Aβ) are two therapeutic targets that are implicated in amyloid light chain amyloidosis and Alzheimer’s disease, respectively. Though crenezumab, an anti-Aβ antibody, is currently unsuccessful, we chose it as a model to computationally design and prepare crenezumab variants, aiming to discover a novel antibody with high affinity to AL fibrils and to establish a technology platform for repurposing amyloid monoclonal antibodies. We successfully re-engineered crenezumab to bind both Aβ42 oligomers and AL fibrils with high binding affinities. It is capable of reversing Aβ42-oligomers-induced cytotoxicity, decreasing the formation of AL fibrils, and alleviating AL-fibrils-induced cytotoxicity in vitro. Our research demonstrated that an amyloid antibody could be engineered by a few mutations to bind new amyloid sequences, providing an efficient way to reposition a therapeutic antibody to target different amyloid diseases.
Optimizing the Ion Conductivity and Mechanical Stability of Polymer Electrolyte Membranes Designed for Use in Lithium Ion Batteries: Combining Imidazolium-Containing Poly(ionic liquids) and Poly(propylene carbonate)
Authors: Kiriy Nataliya , Özenler Sezer , Voigt Pauline , Kobsch Oliver , Meier-Haack Jochen , Arnhold Kerstin , Janke Andreas , Muza Upenyu L. , Geisler Martin , Lederer Albena , Pospiech Doris , Kiriy Anton , Voit Brigitte
Published: January 2024

State-of-the-art Li batteries suffer from serious safety hazards caused by the reactivity of lithium and the flammable nature of liquid electrolytes. This work develops highly efficient solid-state electrolytes consisting of imidazolium-containing polyionic liquids (PILs) and lithium bis(trifluoromethane sulfonyl)imide (LiTFSI). By employing PIL/LiTFSI electrolyte membranes blended with poly(propylene carbonate) (PPC), we addressed the problem of combining ionic conductivity and mechanical properties in one material. It was found that PPC acts as a mechanically reinforcing component that does not reduce but even enhances the ionic conductivity. While pure PILs are liquids, the tricomponent PPC/PIL/LiTFSI blends are rubber-like materials with a Young’s modulus in the range of 100 MPa. The high mechanical strength of the material enables fabrication of mechanically robust free-standing membranes. The tricomponent PPC/PIL/LiTFSI membranes have an ionic conductivity of 10−6 S·cm−1 at room temperature, exhibiting conductivity that is two orders of magnitude greater than bicomponent PPC/LiTFSI membranes. At 60 °C, the conductivity of PPC/PIL/LiTFSI membranes increases to 10−5 S·cm−1 and further increases to 10−3 S·cm−1 in the presence of plasticizers. Cyclic voltammetry measurements reveal good electrochemical stability of the tricomponent PIL/PPC/LiTFSI membrane that potentially ranges from 0 to 4.5 V vs. Li/Li+. The mechanically reinforced membranes developed in this work are promising electrolytes for potential applications in solid-state batteries.
1,6-Hexanediol Is Inducing Homologous Recombination by Releasing BLM from Assemblysomes in Drosophila melanogaster
Authors: Gombás Bence György , Villányi Zoltán
Published: January 2024

We recently demonstrated that 1,6-hexanediol inhibits the formation of assemblysomes. These membraneless cell organelles have important roles in co-translational protein complex assembly and also store halfway translated DNA damage response proteins for a timely stress response. Recognizing the therapeutic potential of 1,6-hexanediol in dismantling assemblysomes likely to be involved in chemo- or radiotherapy resistance of tumor cells, we initiated an investigation into the properties of 1,6-hexanediol. Our particular interest was to determine if this compound induces DNA double-strand breaks by releasing the BLM helicase. Its yeast ortholog Sgs1 was confirmed to be a component of assemblysomes. The BLM helicase induces DNA damage when overexpressed due to the DNA double-strand breaks it generates during its normal function to repair DNA damage sites. It is evident that storing Sgs1 helicase in assemblysomes is crucial to express the full-length functional protein only in the event of DNA damage. Alternatively, if we dissolve assemblysomes using 1,6-hexanediol, ribosome-nascent chain complexes might become targets of ribosome quality control. We explored these possibilities and found, through the Drosophila wing-spot test assay, that 1,6-hexanediol induces DNA double-strand breaks. Lethality connected to recombination events following 1,6-hexanediol treatment can be mitigated by inducing DNA double-strand breaks with X-ray. Additionally, we confirmed that SMC5 recruits DmBLM to DNA damage sites, as knocking it down abolishes the rescue effect of DNA double-strand breaks on 1,6-hexanediol-induced lethality in Drosophila melanogaster.
Age-Dependent Activation of Pannexin1 Function Contributes to the Development of Epileptogenesis in Autosomal Dominant Sleep-related Hypermotor Epilepsy Model Rats
Authors: Fukuyama Kouji , Motomura Eishi , Okada Motohiro
Published: January 2024

To explore the processes of epileptogenesis/ictogenesis, this study determined the age-dependent development of the functional abnormalities in astroglial transmission associated with pannexin1-hemichannel using a genetic rat model of autosomal dominant sleep-related hypermotor epilepsy (ADSHE) named ‘S286L-TG’. Pannexin1 expression in the plasma membrane of primary cultured cortical astrocytes and the orbitofrontal cortex (OFC), which is an ADSHE focus region, were determined using capillary immunoblotting. Astroglial D-serine releases induced by artificial high-frequency oscillation (HFO)-evoked stimulation, the removal of extracellular Ca2+, and the P2X7 receptor agonist (BzATP) were determined using ultra-high performance liquid chromatography (UHPLC). The expressions of pannexin1 in the plasma membrane fraction of the OFC in S286L-TG at four weeks old were almost equivalent when compared to the wild type. The pannexin1 expression in the OFC of the wild type non-statistically decreased age-dependently, whereas that in S286L-TG significantly increased age-dependently, resulting in relatively increasing pannexin1 expression from the 7- (at the onset of interictal discharge) and 10-week-old (after the ADSHE seizure onset) S286L-TG compared to the wild type. However, no functional abnormalities of astroglial pannexin1 expression or D-serine release through the pannexin1-hemichannels from the cultured astrocytes of S286L-TG could be detected. Acutely HFO-evoked stimulation, such as physiological ripple burst (200 Hz) and epileptogenic fast ripple burst (500 Hz), frequency-dependently increased both pannexin1 expression in the astroglial plasma membrane and astroglial D-serine release. Neither the selective inhibitors of pannexin1-hemichannel (10PANX) nor connexin43-hemichannel (Gap19) affected astroglial D-serine release during the resting stage, whereas HFO-evoked D-serine release was suppressed by both inhibitors. The inhibitory effect of 10PANX on the ripple burst-evoked D-serine release was more predominant than that of Gap19, whereas fast ripple burst-evoked D-serine release was predominantly suppressed by Gap19 rather than 10PANX. Astroglial D-serine release induced by acute exposure to BzATP was suppressed by 10PANX but not by Gap19. These results suggest that physiological ripple burst during the sleep spindle plays important roles in the organization of some components of cognition in healthy individuals, but conversely, it contributes to the initial development of epileptogenesis/ictogenesis in individuals who have ADSHE vulnerability via activation of the astroglial excitatory transmission associated with pannexin1-hemichannels.
Information Transmission in G Protein-Coupled Receptors
Authors: Jones Roger D.
Published: January 2024

G protein-coupled receptors (GPCRs) are the largest class of receptors in the human genome and constitute about 30% of all drug targets. In this article, intended for a non-mathematical audience, both experimental observations and new theoretical results are compared in the context of information transmission across the cell membrane. The amount of information actually currently used or projected to be used in clinical settings is a small fraction of the information transmission capacity of the GPCR. This indicates that the number of yet undiscovered drug targets within GPCRs is much larger than what is currently known. Theoretical studies with some experimental validation indicate that localized heat deposition and dissipation are key to the identification of sites and mechanisms for drug action.