bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond acute infection: molecular mechanisms underpinning cardiovascular complications in long COVID
Authors: Mostafa Roba Hamed , Moustafa Ahmed
Published: March 2024

SARS-CoV-2, responsible for the global COVID-19 pandemic, has manifested significant cardiovascular implications for the infected population. These cardiovascular repercussions not only linger beyond the initial phase of illness but have also been observed in individuals who remain asymptomatic. This extended and pervasive impact is often called the post-acute COVID-19 syndrome (PACS) or “Long COVID”. With the number of confirmed global cases approaching an alarming 756 million, the multifaceted challenges of Long COVID are undeniable. These challenges span from individual health complications to considerable burdens on worldwide healthcare systems. Our review comprehensively examines the complications of the persistent cardiovascular complications associated with COVID-19. Furthermore, we shed light on emerging therapeutic strategies that promise to manage and possibly mitigate these complications. We also introduce and discuss the profound concerns regarding the potential transgenerational repercussions of SARS-CoV-2, emphasizing the need for a proactive and informed approach to future research and clinical practice.
Association of pulse pressure and aortic root diameter in elderly Chinese patients with chronic heart failure
Authors: Chen Lu , Xie Wenhui , Hong Xuhui , Hong Huashan
Published: March 2024

Background

High pulse pressure (PP) and aortic root diameter (AoD) are hallmarks of arterial stiffness or vascular aging and they are considered as risk factors for age-related cardiovascular disease, including heart failure (HF). However, the relationship between PP and AoD in patients with heart failure (HF) is uncertain. This study aimed to evaluate the relationship between PP and AoD in the middle-aged and the elderly with HF.

Methods

A total of 1,027 Chinese middle-aged and elderly patients with HF, including HF with reduced ejection fraction (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF) were included in this study. Pearson correlation analysis was used to evaluate the relationship between PP and AoD in the three types of HF. Multiple linear regression analysis was performed to assess the factors that affected AoD. Multivariate logistic regression was performed to determine the association between the PP level quartiles and AoD. The results were validated in an independent dataset included a total of 378 consecutive patients with HFrEF hospitalized at the Pingtan Branch of Fujian Medical University Union Hospital (Fujian, China).

Results

There was a positive correlation between PP and AoD in the middle-aged and the elderly with HFrEF. Multiple linear regression analysis revealed that PP, age, and body mass index (BMI) were independently correlated with AoD in HFrEF patients. In multivariate logistic regression analysis, an increased risk of aortic root dilation was observed in the highest quartile of the PP level compared with the lowest quartile. Age significantly interacted with PP (p = 0.047). A significant association between PP levels and AoD was only observed in patients ≥ 65 years old, but not in patients < 65 years old. In the validation dataset, PP was independently related to AoD in patients with HFrEF (β = 0.205, p = 0.001).

Conclusions

PP level was independently and positively associated with AoD, especially in the elderly with HFrEF, but not in patients with HFmrEF and HFpEF. Arterial stiffening or vascular aging may play a certain role in the elderly HFrEF patients.
A scalable MapReduce-based design of an unsupervised entity resolution system
Authors: Hagan Nicholas Kofi Akortia , Talburt John R. , Anderson Kris E. , Hagan Deasia
Published: March 2024

Traditional data curation processes typically depend on human intervention. As data volume and variety grow exponentially, organizations are striving to increase efficiency of their data processes by automating manual processes and making them as unsupervised as possible. An additional challenge is to make these unsupervised processes scalable to meet the demands of increased data volume. This paper describes the parallelization of an unsupervised entity resolution (ER) process. ER is a component of many different data curation processes because it clusters records from multiple data sources that refer to the same real-world entity, such as the same customer, patient, or product. The ability to scale ER processes is particularly important because the computation effort of ER increases quadratically with data volume. The Data Washing Machine (DWM) is an already proposed unsupervised ER system which clusters references from diverse data sources. This work aims at solving the single-threaded nature of the DWM by adopting the parallelization nature of Hadoop MapReduce. However, the proposed parallelization method can be applied to both supervised systems, where matching rules are created by experts, and unsupervised systems, where expert intervention is not required. The DWM uses an entropy measure to self-evaluate the quality of record clustering. The current single-threaded implementations of the DWM in Python and Java are not scalable beyond a few 1,000 records and rely on large, shared memory. The objective of this research is to solve the major two shortcomings of the current design of the DWM which are the creation and usage of shared memory and lack of scalability by leveraging on the power of Hadoop MapReduce. We propose Hadoop Data Washing Machine (HDWM), a MapReduce implementation of the legacy DWM. The scalability of the proposed system is displayed using publicly available ER datasets. Based on results from our experiment, we conclude that HDWM can cluster from 1,000's to millions of equivalent references using multiple computational nodes with independent RAM and CPU cores.
City composition and accessibility statistics in and around Paris
Authors: Thaury Marie-Olive , Genet Simon , Maurice Léopold , Tubaro Paola , Berkemer Sarah J.
Published: March 2024

Introduction

Is Paris a 15-min city, where inhabitants can access essential amenities such as schools and shops with a 15-min walk or bike ride? The concept of a 15-min (more generally, X-minute) city was launched in the French capital and was part of the current mayor's plan in her latest re-election campaign. Yet, its fit with the existing urban structure had not been previously assessed.

Methods

This article combines open map data from a large participatory project and geo-localized socio-economic data from official statistics to fill this gap.

Results

We show that, while the city of Paris is rather homogeneous, it is nonetheless characterized by remarkable inequalities between a highly accessible city center (though with some internal differences in terms of types of amenities) and a less well-equipped periphery, where lower-income neighborhoods are more often found. The heterogeneity increases if we consider Paris together with its immediate surroundings, the "Petite Couronne," where large numbers of daily commuters and other users of city facilities live.

Discussion

We thus conclude that successful implementation of the X-minute-city concept requires addressing existing socio-economic inequalities, and that especially in big cities, it should be extended beyond the narrow boundaries of the municipality itself to encompass the larger area around it.
Protracted post-glacial hydrocarbon seepage in the Barents Sea revealed by U–Th dating of seep carbonates
Authors: Himmler Tobias , Wagner Doris , Sahy Diana , Vadakkepuliyambatta Sunil , Chand Shyam , Martma Tõnu , Kirsimäe Kalle , Mattingsdal Rune , Panieri Giuliana , Bünz Stefan , Condon Daniel J. , Knies Jochen , Lepland Aivo
Published: March 2024

The hydrocarbon seepage chronology during deglaciation across the formerly glaciated Barents Sea was established using uranium-thorium (U–Th) dating of seep carbonates. Seep carbonates were sampled with remotely operated vehicles (ROV) from the seafloor at three active hydrocarbon seeps (water depth 156–383 m), located in the north-west (Storfjordrenna), north-central (Storbanken High), and south-west (Loppa High) Barents Sea. Overall, the U–Th dates range from 13.5 to 1.2 thousand years (ka) before present, indicating episodic seep carbonate formation since the late Pleistocene throughout the Holocene. The new U–Th dates indicate protracted post-glacial gas seepage, congruent with previously published seep carbonate ages from the south-west Barents Sea. Gas hydrate dissociation and associated seep carbonate formation occurred at Storfjordrenna between ≈6 and 1.2 ka, and around 13.5 and 6 ka at Storbanken. Early and late Holocene seep carbonate ages from Loppa High support post-glacial seismic activity as potential seepage trigger mechanism.
Associations between type 2 diabetes mellitus and chronic liver diseases: evidence from a Mendelian randomization study in Europeans and East Asians
Authors: Zhao Yue , Li Di , Shi Hanyu , Liu Wei , Qiao Jiaojiao , Wang Shanfu , Geng Yiwei , Liu Ruiying , Han Feng , Li Jia , Li Wei , Wu Fengyun
Published: March 2024

Objective

Multiple observational studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and chronic liver diseases (CLDs). However, the causality of T2DM on CLDs remained unknown in various ethnic groups.

Methods

We obtained instrumental variables for T2DM and conducted a two-sample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results.

Results

In Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271-1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of NAFLD (ALT: IVW OR=0.9752, 95%CI 0.9597-0.9909, p=0.0021; AST: IVW OR=0.9673, 95%CI, 0.9528-0.9821, p=1.67e-5), and HCV (IVW: OR=0.9289, 95%CI, 0.8852-0.9747, p=0.0027). Notably, no causal association was found between T2DM and HCC, viral hepatitis, or HBV.

Conclusion

Our MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.
Home range size of Tengmalm’s owl offspring during the post-fledging dependence period in Central and North Europe
Authors: Stehlíková Sovadinová Simona , Kouba Marek , Ševčík Michal , Tulis Filip , Bušina Tomáš , Korpimäki Erkki
Published: March 2024

A greater knowledge of the intrinsic and extrinsic factors of animal home range (HR) formation can help us to understand the fundamental biological issues underlying, for instance, movement patterns, habitat selection and survival. However, very little is known about the HRs of birds of prey fledglings, even though the post-fledging phase is recognised as crucial due to the high mortality of juvenile birds. We radio-tracked 138 Tengmalm’s owl (Aegolius funereus) fledglings from 43 broods to determine their HRs during the post-fledging dependence period and to investigate the factors affecting their sizes. The study was conducted during four breeding seasons in Czechia and two seasons in Finland. The mean fledglings’ HR size calculated according to the 95% IID Kernel Density Estimation method was 63.7 ± 43.9 ha (± SD; n = 71) during nocturnal activity and 52.0 ± 46.1 ha (n = 63) during diurnal roosting. The sizes of both nocturnal activity and diurnal roosting HRs increased with the longer individual duration of the post-fledging dependence period and also the higher rank of hatching within a brood. Diurnal roosting HRs were two times smaller in the Czech site, probably because of the very limited number of dense forest patches suitable for roosting as a legacy of the air pollution calamity in the 1970s, during which most coniferous stands died out. There was no difference in the size of nocturnal activity HR between the two study areas, although they differed markedly in terms of night length, altitude, weather, and forest age, structure and composition. This suggests that environmental factors are not decisive in determining the size of nocturnal activity HRs of Tengmalm’s owl fledglings. Since the diurnal HRs always occurred within the area of the nocturnal HRs, we suggest that conservation of the densest and preferably oldest forest stands within the areas of the study species occurrence may offer straightforward conservation tasks for protecting Tengmalm’s owl fledglings and also other species.
TRIM28 facilitates type I interferon activation by targeting TBK1
Authors: Hua Fang , Nass Tim , Parvatiyar Kislay
Published: March 2024

Type I interferons play a fundamental role in innate host defense against viral infections by eliciting the induction of an antiviral gene program that serves to inhibit viral replication. Activation of type I interferon is regulated by the IRF3 transcription factor, which undergoes phosphorylation-dependent activation by the upstream kinase, TBK1, during viral infection. However, the mechanisms by which TBK1 achieves activation to support signaling to IRF3 remain incompletely understood. Here we identified the E3 ubiquitin ligase, tripartite motif containing 28 (TRIM28), as a positive regulator of type I interferon activation by facilitating TBK1 signaling. Genetic deletion of TRIM28 via CRISPR-Cas9 editing resulted in impaired type I interferon activation upon both RNA and DNA virus challenge, corresponding with increased susceptibility to virus infections in TRIM28 knockout cells. Mechanistically, TRIM28 interacted with TBK1 and mediated the assembly of K63-linked ubiquitin chains onto TBK1, a post-translational modification shown to augment TBK1 signal transmission events. TRIM28 knockout cells further displayed defective TBK1 phosphorylation and complex assembly with IRF3, resulting in impaired IRF3 phosphorylation. Altogether, our data demonstrate TBK1 to be a novel substrate for TRIM28 and identify TRIM28 as an essential regulatory factor in controlling innate antiviral immune responses.
Cancer cells and viruses share common glycoepitopes: exciting opportunities toward combined treatments
Authors: Roy René
Published: March 2024

Aberrant glycosylation patterns of glycoproteins and glycolipids have long been recognized as one the major hallmarks of cancer cells that has led to numerous glycoconjugate vaccine attempts. These abnormal glycosylation profiles mostly originate from the lack of key glycosyltransferases activities, mutations, over expressions, or modifications of the requisite chaperone for functional folding. Due to their relative structural simplicity, O-linked glycans of the altered mucin family of glycoproteins have been particularly attractive in the design of tumor associated carbohydrate-based vaccines. Several such glycoconjugate vaccine formulations have generated potent monoclonal anti-carbohydrate antibodies useful as diagnostic and immunotherapies in the fight against cancer. Paradoxically, glycoproteins related to enveloped viruses also express analogous N- and O-linked glycosylation patterns. However, due to the fact that viruses are not equipped with the appropriate glycosyl enzyme machinery, they need to hijack that of the infected host cells. Although the resulting N-linked glycans are very similar to those of normal cells, some of their O-linked glycan patterns often share the common structural simplicity to those identified on tumor cells. Consequently, given that both cancer cells and viral glycoproteins share both common N- and O-linked glycoepitopes, glycoconjugate vaccines could be highly attractive to generate potent immune responses to target both conditions.
Interferon lambda in respiratory viral infection: immunomodulatory functions and antiviral effects in epithelium
Authors: Liu Yong-Guang , Jin Su-Wei , Zhang Shan-Shan , Xia Tian-Ji , Liao Yong-Hong , Pan Rui-Le , Yan Ming-Zhu , Chang Qi
Published: March 2024

Type III interferon (IFN-λ), a new member of the IFN family, was initially considered to possess antiviral functions similar to those of type I interferon, both of which are induced via the JAK/STAT pathway. Nevertheless, recent findings demonstrated that IFN-λ exerts a nonredundant antiviral function at the mucosal surface, preferentially produced in epithelial cells in contrast to type I interferon, and its function cannot be replaced by type I interferon. This review summarizes recent studies showing that IFN-λ inhibits the spread of viruses from the cell surface to the body. Further studies have found that the role of IFN-λ is not only limited to the abovementioned functions, but it can also can exert direct and/or indirect effects on immune cells in virus-induced inflammation. This review focuses on the antiviral activity of IFN-λ in the mucosal epithelial cells and its action on immune cells and summarizes the pathways by which IFN-λ exerts its action and differentiates it from other interferons in terms of mechanism. Finally, we conclude that IFN-λ is a potent epidermal antiviral factor that enhances the respiratory mucosal immune response and has excellent therapeutic potential in combating respiratory viral infections.
Modulation of myeloid-derived suppressor cell functions by oral inflammatory diseases and important oral pathogens
Authors: García-Arévalo Fernando , Leija-Montoya Ana Gabriela , González-Ramírez Javier , Isiordia-Espinoza Mario , Serafín-Higuera Idanya , Fuchen-Ramos Dulce Martha , Vazquez-Jimenez J. Gustavo , Serafín-Higuera Nicolas
Published: March 2024

The oral cavity presents a diverse microbiota in a dynamic balance with the host. Disruption of the microbial community can promote dysregulation of local immune response which could generate oral diseases. Additionally, alterations in host immune system can result in inflammatory disorders. Different microorganisms have been associated with establishment and progression of the oral diseases. Oral cavity pathogens/diseases can modulate components of the inflammatory response. Myeloid-derived suppressor cells (MDSCs) own immunoregulatory functions and have been involved in different inflammatory conditions such as infectious processes, autoimmune diseases, and cancer. The aim of this review is to provide a comprehensive overview of generation, phenotypes, and biological functions of the MDSCs in oral inflammatory diseases. Also, it is addressed the biological aspects of MDSCs in presence of major oral pathogens. MDSCs have been mainly analyzed in periodontal disease and Sjögren’s syndrome and could be involved in the outcome of these diseases. Studies including the participation of MDSCs in other important oral diseases are very scarce. Major oral bacterial and fungal pathogens can modulate expansion, subpopulations, recruitment, metabolism, immunosuppressive activity and osteoclastogenic potential of MDSCs. Moreover, MDSC plasticity is exhibited in presence of oral inflammatory diseases/oral pathogens and appears to be relevant in the disease progression and potentially useful in the searching of possible treatments. Further analyses of MDSCs in oral cavity context could allow to understand the contribution of these cells in the fine-tuned balance between host immune system and microorganism of the oral biofilm, as well as their involvement in the development of oral diseases when this balance is altered.
Free vibration analysis of functionally graded graphene platelet-reinforced metal foam doubly curved panel
Authors: Zhang Li-Li , Zhao Li-Cai , Lang Song-Jun , Asemi Kamran
Published: March 2024

In this research, free vibration characteristics of functionally graded metal foam doubly curved panels reinforced with graphene platelets and with porosities have been surveyed. Halpin Tsai's approach is utilized for extracting the effective Young modulus of porous metal foam nanocomposite and also the effective density of nanocomposite porous doubly curved shell panel is estimated by using an extended rule of mixture. The FSDT hypothesis is utilized for determining the displacement field and the Finite element and Hamilton principle are utilized for deriving the mass and stiffness matrices of the structure. Finally, the influences of several variables such as porosity distribution, porosity coefficient, GPL dispersion pattern, the weight fraction of Nanofillers, and span angles on the free vibrations characteristics of doubly curved shell panels with FG porosities and reinforced by graphene platelet have been reported in detail.
A randomized trial of a wearable UV dosimeter for skin cancer prevention
Authors: Dumont Emmanuel L. P. , Kaplan Peter D. , Do Catherine , Banerjee Shayak , Barrer Melissa , Ezzedine Khaled , Zippin Jonathan H. , Varghese George I.
Published: March 2024

Background

Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. Despite guidelines on ultraviolet (UV) avoidance, it remains difficult for people to assess their exposure, as UV is invisible and the onset of UV-induced symptoms is delayed.

Methods

In a prospective randomized trial, 97 elderly patients with a history of actinic keratoses (AK) were followed over 6 months. Fifty patients received UV counseling from a dermatologist and a wearable UV dosimeter that provided real-time and cumulative UV exposure. Forty-seven patients received only UV counseling from a dermatologist.

Results

Over 75% of participants recorded UV exposure at least once a week during the summer. After 6 months of intervention, when comparing the device group to the control group, we observed a non-significant 20% lower ratio of incidence rates of AKs (95% CI = [−41, 55%], p-value = 0.44) and a significant 95% lower ratio of incidence rates of NMSCs (95% CI = [33, 99.6%], p-value = 0.024). Surveys demonstrated that the control group’s score in self-perceived ability to participate in social activities significantly increased by 1.2 (p-value = 0.04), while in the device group, this score non-significantly decreased by 0.9 (p-value = 0.1). We did not observe changes, or between-group differences, in anxiety and depression surveys.

Conclusion

This pilot clinical trial has a short duration and a small sample size. However, device adherence and quality of life questionnaires suggest a smartphone-connected wearable UV dosimeter is well accepted by an elderly population. This trial also indicates that a wearable UV dosimeter may be an effective behavioral change tool to reduce NMSC incidence in an elderly population with a prior history of AKs.

Clinical trial registration: clinicaltrials.gov, identifier NCT03315286.
Chronic alcohol-induced long-lasting working memory deficits are associated with altered histone H3K9 dimethylation in the prefrontal cortex
Authors: De Clerck Mael , Manguin Martin , Henkous Nadia , d’Almeida Marion N. , Beracochea Daniel , Mons Nicole
Published: March 2024

Introduction

Epigenetic modifications have emerged as key contributors to the enduring behavioral, molecular and epigenetic neuroadaptations during withdrawal from chronic alcohol exposure. The present study investigated the long-term consequences of chronic alcohol exposure on spatial working memory (WM) and associated changes of transcriptionally repressive histone H3 lysine 9 dimethylation (H3K9me2) in the prefrontal cortex (PFC).

Methods

Male C57BL/6 mice were allowed free access to either 12% (v/v) ethanol for 5 months followed by a 3-week abstinence period or water. Spatial WM was assessed through the spontaneous alternation T-maze test. Alcoholic and water mice received daily injections of GABAB agonist baclofen or saline during alcohol fading and early withdrawal. Global levels of histone modifications were determined by immunohistochemistry.

Results

Withdrawal mice displayed WM impairments along with reduced prefrontal H3K9me2 levels, compared to water-drinking mice. The withdrawal-induced decrease of H3K9me2 occurred concomitantly with increased level of permissive H3K9 acetylation (H3K9ac) in the PFC. Baclofen treatment rescued withdrawal-related WM deficits and fully restored prefrontal H3K9me2 and H3K9ac. Alcohol withdrawal induced brain region-specific changes of H3K9me2 and H3K9ac after testing, with significant decreases of both histone marks in the dorsal hippocampus and no changes in the amygdala and dorsal striatum. Furthermore, the magnitude of H3K9me2 in the PFC, but not the hippocampus, significantly and positively correlated with individual WM performances. No correlation was observed between H3K9ac and behavioral performance. Results also indicate that pre-testing intraperitoneal injection of UNC0642, a selective inhibitor of histone methyltransferase G9a responsible for H3K9me2, led to WM impairments in water-drinking and withdrawal-baclofen mice. Collectively, our results demonstrate that alcohol withdrawal induced brain-region specific alterations of H3K9me2 and H3K9ac, an effect that persisted for at least three weeks after cessation of chronic alcohol intake.

Conclusion

The findings suggest a role for long-lasting decreased H3K9me2 specifically in the PFC in the persistent WM impairments related to alcohol withdrawal.
Brain-inspired modular echo state network for EEG-based emotion recognition
Authors: Yang Liuyi , Wang Zhaoze , Wang Guoyu , Liang Lixin , Liu Meng , Wang Junsong
Published: March 2024

Previous studies have successfully applied a lightweight recurrent neural network (RNN) called Echo State Network (ESN) for EEG-based emotion recognition. These studies use intrinsic plasticity (IP) and synaptic plasticity (SP) to tune the hidden reservoir layer of ESN, yet they require extra training procedures and are often computationally complex. Recent neuroscientific research reveals that the brain is modular, consisting of internally dense and externally sparse subnetworks. Furthermore, it has been proved that this modular topology facilitates information processing efficiency in both biological and artificial neural networks (ANNs). Motivated by these findings, we propose Modular Echo State Network (M-ESN), where the hidden layer of ESN is directly initialized to a more efficient modular structure. In this paper, we first describe our novel implementation method, which enables us to find the optimal module numbers, local and global connectivity. Then, the M-ESN is benchmarked on the DEAP dataset. Lastly, we explain why network modularity improves model performance. We demonstrate that modular organization leads to a more diverse distribution of node degrees, which increases network heterogeneity and subsequently improves classification accuracy. On the emotion arousal, valence, and stress/calm classification tasks, our M-ESN outperforms regular ESN by 5.44, 5.90, and 5.42%, respectively, while this difference when comparing with adaptation rules tuned ESNs are 0.77, 5.49, and 0.95%. Notably, our results are obtained using M-ESN with a much smaller reservoir size and simpler training process.
Human mutations in SLITRK3 implicated in GABAergic synapse development in mice
Authors: Efthymiou Stephanie , Han Wenyan , Ilyas Muhammad , Li Jun , Yu Yichao , Scala Marcello , Malintan Nancy T. , Ilyas Muhammad , Vavouraki Nikoleta , Mankad Kshitij , Maroofian Reza , Rocca Clarissa , Salpietro Vincenzo , Lakhani Shenela , Mallack Eric J. , Palculict Timothy Blake , Li Hong , Zhang Guojun , Zafar Faisal , Rana Nuzhat , Takashima Noriko , Matsunaga Hayato , Manzoni Claudia , Striano Pasquale , Lythgoe Mark F. , Aruga Jun , Lu Wei , Houlden Henry
Published: March 2024

This study reports on biallelic homozygous and monoallelic de novo variants in SLITRK3 in three unrelated families presenting with epileptic encephalopathy associated with a broad neurological involvement characterized by microcephaly, intellectual disability, seizures, and global developmental delay. SLITRK3 encodes for a transmembrane protein that is involved in controlling neurite outgrowth and inhibitory synapse development and that has an important role in brain function and neurological diseases. Using primary cultures of hippocampal neurons carrying patients’ SLITRK3 variants and in combination with electrophysiology, we demonstrate that recessive variants are loss-of-function alleles. Immunostaining experiments in HEK-293 cells showed that human variants C566R and E606X change SLITRK3 protein expression patterns on the cell surface, resulting in highly accumulating defective proteins in the Golgi apparatus. By analyzing the development and phenotype of SLITRK3 KO (SLITRK3–/–) mice, the study shows evidence of enhanced susceptibility to pentylenetetrazole-induced seizure with the appearance of spontaneous epileptiform EEG as well as developmental deficits such as higher motor activities and reduced parvalbumin interneurons. Taken together, the results exhibit impaired development of the peripheral and central nervous system and support a conserved role of this transmembrane protein in neurological function. The study delineates an emerging spectrum of human core synaptopathies caused by variants in genes that encode SLITRK proteins and essential regulatory components of the synaptic machinery. The hallmark of these disorders is impaired postsynaptic neurotransmission at nerve terminals; an impaired neurotransmission resulting in a wide array of (often overlapping) clinical features, including neurodevelopmental impairment, weakness, seizures, and abnormal movements. The genetic synaptopathy caused by SLITRK3 mutations highlights the key roles of this gene in human brain development and function.
An integrative morpho-molecular approach in malignant ectomesenchymoma diagnosis: report of a new paediatric case and a review of the literature
Authors: Pellegrino Francesco , Tirtei Elisa , Divincenzo Federico , Campello Anna , Rubino Carlotta , Augustoni Elisabetta , Linari Alessandra , Asaftei Sebastian Dorin , Fagioli Franca
Published: March 2024

Introduction

Malignant ectomesenchymoma (MEM) is a soft tissue tumour, consisting of both malignant neuroectodermal elements and one or more mesenchymal elements.

Case presentation and review of the literature

Here we describe the case of a 6-months-old male, previously treated in another hospital for abdominal rhabdomyosarcoma (RMS). Histological re-examination demonstrated that the tumour had mesenchymal and neuroectodermal elements components, with a new diagnosis of abdominal-pelvic MEM. A Next-Generation Sequencing (NGS) analysis was performed on a surgical tumour specimen and revealed the presence of a somatic mutation, already reported in MEM cases. We carried out a review of the literature and we found 33 new cases of MEM since the last review. We reported the clinic-pathologic features of new cases of MEM, highlighting the role of molecular studies in supporting the diagnosis of this ambiguous tumours.

Conclusion

We promote the importance of a diagnosis based on an integrative morpho-molecular approach, that routinely include molecular analysis and the use of bioinformatic mutation detection tools, to support diagnostic and therapeutical queries and to highlight tumour biology and behaviour.
HMGB1/RAGE axis in tumor development: unraveling its significance
Authors: Fan Anqi , Gao Mengxiang , Tang Xuhuan , Jiao Mengya , Wang Chenchen , Wei Yingying , Gong Quan , Zhong Jixin
Published: March 2024

High mobility group protein 1 (HMGB1) plays a complex role in tumor biology. When released into the extracellular space, it binds to the receptor for advanced glycation end products (RAGE) located on the cell membrane, playing an important role in tumor development by regulating a number of biological processes and signal pathways. In this review, we outline the multifaceted functions of the HMGB1/RAGE axis, which encompasses tumor cell proliferation, apoptosis, autophagy, metastasis, and angiogenesis. This axis is instrumental in tumor progression, promoting tumor cell proliferation, autophagy, metastasis, and angiogenesis while inhibiting apoptosis, through pivotal signaling pathways, including MAPK, NF-κB, PI3K/AKT, ERK, and STAT3. Notably, small molecules, such as miRNA-218, ethyl pyruvate (EP), and glycyrrhizin exhibit the ability to inhibit the HMGB1/RAGE axis, restraining tumor development. Therefore, a deeper understanding of the mechanisms of the HMGB1/RAGE axis in tumors is of great importance, and the development of inhibitors targeting this axis warrants further exploration.
A causality between fruit consumption and colorectal cancer: a two-sample Mendelian randomization analysis
Authors: Yang Li
Published: March 2024

Background

Colorectal cancer (CRC) significantly threatens human health with increasing incidence and mortality. A debate continues whether fruit consumption is associated with CRC, despite dietary habits having an impact on the disease. The study aims to examine the causal relationship between fruit consumption and CRC based on a two-sample Mendelian randomization method (MR).

Methods

Summary statistics for fruit consumption and CRC were obtained from the UK Biobank and the FinnGen Consortium, respectively. Analysis methods used in this study included the inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode. Heterogeneity and horizontal pleiotropy were also assessed. Additionally, a leave-one-out analysis was performed to validate the robustness of the results.

Results

We found that fruit consumption was associated with a reduction in CRC risk by the IVW method (P = 0.021). This protective effect was predominantly observed in males (OR 0.374; 95% CI: 0.157-0.892; P = 0.027), while no protective effect was noted in females. However, causal correlations were not observed upon analyzing 16 individual types of fruits. Moreover, our results were unlikely to be influenced by horizontal pleiotropy and heterogeneity. Leave-one-out analysis confirmed the stability of the results.

Conclusion

Our findings suggest that a genetic predisposition for fruit consumption may be protective against CRC, underscoring the need for further research to elucidate the underlying mechanisms and dietary patterns involved.
JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target
Authors: Jiang Heng , Yang Junjie , Li Tao , Wang Xinyu , Fan Zhongcai , Ye Qiang , Du Yanfei
Published: March 2024

Cardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular matrix (ECM) components produced by activated myofibroblasts, which leads to fibrotic scar formation and subsequent cardiac dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis. This lack is largely because the molecular mechanisms of cardiac fibrosis remain unclear despite extensive research. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is an extensively present intracellular signal transduction pathway and can regulate a wide range of biological processes, including cell proliferation, migration, differentiation, apoptosis, and immune response. Various upstream mediators such as cytokines, growth factors and hormones can initiate signal transmission via this pathway and play corresponding regulatory roles. STAT3 is a crucial player of the JAK/STAT pathway and its activation is related to inflammation, malignant tumors and autoimmune illnesses. Recently, the JAK/STAT3 signaling has been in the spotlight for its role in the occurrence and development of cardiac fibrosis and its activation can promote the proliferation and activation of CFs and the production of ECM proteins, thus leading to cardiac fibrosis. In this manuscript, we discuss the structure, transactivation and regulation of the JAK/STAT3 signaling pathway and review recent progress on the role of this pathway in cardiac fibrosis. Moreover, we summarize the current challenges and opportunities of targeting the JAK/STAT3 signaling for the treatment of fibrosis. In summary, the information presented in this article is critical for comprehending the role of the JAK/STAT3 pathway in cardiac fibrosis, and will also contribute to future research aimed at the development of effective anti-fibrotic therapeutic strategies targeting the JAK/STAT3 signaling.
Targeted intracellular delivery of dimeric STINGa by two pHLIP peptides for treatment of solid tumors
Authors: Moshnikova Anna , DuPont Michael , Iraca Marissa , Klumpp Craig , Visca Hannah , Allababidi Dana , Pelzer Phoebe , Engelman Donald M. , Andreev Oleg A. , Reshetnyak Yana K.
Published: March 2024

Introduction: We have developed a delivery approach that uses two pHLIP peptides that collaborate in the targeted intracellular delivery of a single payload, dimeric STINGa (dMSA).

Methods: dMSA was conjugated with two pHLIP peptides via S-S cleavable self-immolating linkers to form 2pHLIP-dMSA.

Results: Biophysical studies were carried out to confirm pH-triggered interactions of the 2pHLIP-dMSA with membrane lipid bilayers. The kinetics of linker self-immolation and dMSA release, the pharmacokinetics, the binding to plasma proteins, the stability of the agent in plasma, the targeting and resulting cytokine activation in tumors, and the biodistribution of the construct was investigated. This is the first study demonstrating that combining the energy of the membrane-associated folding of two pHLIPs can be utilized to enhance the targeted intracellular delivery of large therapeutic cargo payloads.

Discussion: Linking two pHLIPs to the cargo extends blood half-life, and targeted delivery of dimeric STINGa induces tumor eradication and the development of robust anti-cancer immunity.
Quadriceps muscle atrophy after non-invasive anterior cruciate ligament injury: evidence linking to autophagy and mitophagy
Authors: Noh Sung Gi , Ahn Ahram , Davi Steven M. , Lepley Lindsey K. , Kwon Oh Sung
Published: March 2024

Introduction: Anterior cruciate ligament (ACL) injury is frequently accompanied by quadriceps muscle atrophy, a process closely linked to mitochondrial health and mitochondria-specific autophagy. However, the temporal progression of key quadricep atrophy-mediating events following ACL injury remains poorly understood. To advance our understanding, we conducted a longitudinal study to elucidate key parameters in quadriceps autophagy and mitophagy.

Methods: Long-Evans rats were euthanized at 7, 14, 28, and 56 days after non-invasive ACL injury that was induced via tibial compression overload; controls were not injured. Vastus lateralis muscle was extracted, and subsequent immunoblotting analysis was conducted using primary antibodies targeting key proteins involved in autophagy and mitophagy cellular processes.

Results: Our findings demonstrated dynamic changes in autophagy and mitophagy markers in the quadriceps muscle during the recovery period after ACL injury. The early response to the injury was characterized by the induction of autophagy at 14 days (Beclin1), indicating an initial cellular response to the injury. Subsequently, at 14 days we observed increase in the elongation of autophagosomes (Atg4B), suggesting a potential remodeling process. The autophagosome flux was also augmented between 14- and 28 days (LC3-II/LC3-I ratio and p62). Notably, at 56 days, markers associated with the elimination of damaged mitochondria were elevated (PINK1, Parkin, and VDAC1), indicating a possible ongoing cellular repair and restoration process.

Conclusion: These data highlight the complexity of muscle recovery after ACL injury and underscore the overlooked but crucial role of autophagy and mitophagy in promoting the recovery process.
Autonomous sensory Meridian response as a physically felt signature of positive and negative emotions
Authors: Leung Wai Lam , Romano Daniela M.
Published: March 2024

Introduction

Current research on Autonomous Sensory Meridian Response (ASMR) assumes that ASMR is always accompanied by contentment, and it is distinct from frisson due to positive emotions. Thus, research investigations tend to limit their scope to solely focusing on the sensation of relaxation that ASMR induces. This study explores whether it is possible to have a different emotional experience and still perceive ASMR, testing the theory of ASMR as an amplifier of pre-existing emotion instead of a determination of positive affect.

Methods

The emotional arousal and valence, and mood changes of 180 ASMR-capable and incapable individuals were analysed using questionnaires after altering the affective interpretation associated with auditory ASMR (tapping) with visual priming to examine whether the primed emotion (fearful, relaxing, or neutral) could be amplified.

Results

It was found that an ASMR response occurred in all priming conditions, including the fear priming group. No significant difference was found in the emotional outcome or mood of the neutral and relaxing priming groups. Upon comparison with ASMR-incapable individuals, both the relaxing and neutral priming groups demonstrated the same affect, but greater potent for ASMR-capable. Individuals who appraised ASMR after visual fear priming demonstrated a significant decrease in positive emotional valence and increased arousal.

Conclusion

The findings suggest that ASMR occurs in both positive and negative emotional situations, suppressing contentment induction if ASMR stimuli are interpreted negatively and amplifying contentment when interpreted positively. While more research is needed, the results highlight that ASMR and frisson might describe the same phenomenon, both a physically felt signature of emotion. Therapeutic usage of ASMR should carefully select appropriate stimuli that emphasise contentment to avoid potential health risks associated with negative emotions until a further understanding of ASMR’s affective parameters has been established.
Characterization of students with high intellectual capacity: the approach in the Portuguese school context and importance of teacher training for their educational inclusion
Authors: García-Perales Ramón , Rocha Alberto , Aguiar Ana , Almeida Ana Isabel S.
Published: March 2024

This paper takes a terminological approach to the concept of high intellectual abilities, highlighting the distinctive aspects of the way it is addressed in the Portuguese educational context. It outlines the existing conceptual differentiation in the field of higher abilities, emphasizing how the main characteristics are described and including the strengths and weaknesses of current teaching and learning processes in Portugal. As we will show, educational work with these students in Portuguese schools is characterized by unequal regulation compared to other educational needs, by an imbalance of educational processes aimed at these gifted students, and by clear underdiagnosis that sometimes leads to them being ignored in the classroom, with the consequent harm that this can cause to their overall development and to their academic and professional careers. The paper emphasizes the importance of teacher training in Portugal as an aspect that could be key to reversing, as far as possible, this gap in educational processes—which currently include educational inclusion for all their students as part of the key action principles in the Portuguese educational system.
Psychometric properties of the wellbeing literacy 6-item scale in Chinese military academy cadets
Authors: Jia Zhen , Zheng Fangfang , Wang Feifei , Yang Guoyu
Published: March 2024

Background

Positive psychology is a vibrant field of study, and conceptualizations of the components of well-being have received a great deal of attention from researchers. The study of well-being literacy thus provides an innovative perspective for enhancing and sustaining individuals’ experiences of well-being.

Objective

This study aimed to examine the psychometric properties of the wellbeing literacy 6-item (Well-Lit 6) scale in Chinese military academy cadets.

Methods

A total of 3,218 undergraduate students from five military academies in China were recruited to complete questionnaires online.

Results

(1) The items of the scale showed high discrimination; (2) The alpha coefficient of the scale was 0.986 and the split-half reliability was 0.981, indicating high homogeneous reliability and split-half reliability; (3) The scale model fitted well and displayed structural validity; (4) The correlation between well-being literacy and related indicators was significant, and the calibration correlation and convergent-discriminant validity of the scale were high; (5) After gradually adding demographic variables, known predictors factors and well-being literacy, the ∆R2 for subjective well-being, life satisfaction, depression, and anxiety ranged from 0.036 to 0.067, 0.184 to 0.340, and 0.009 to 0.017, respectively, showing high incremental validity; (6) the total well-being literacy scores differed significantly by gender, grade, and parenting style.

Conclusion

The Chinese version of the Well-Lit 6 is reliable and valid in predicting and accessing the subjective well-being, life satisfaction, emotion regulation, and psychological resilience of Chinese military academy cadets.
Stress and sport performance: a PNEI multidisciplinary approach
Authors: Tossici Giulia , Zurloni Valentino , Nitri Andrea
Published: March 2024

Stress control is essential for avoiding a state of anxiety in sport competitions, as this state may have negative effects on other psychological variables of athletes, decreasing their self-confidence and harming their attentional control. In the present contribution a distress intervention model developed from a PNEI perspective will be sketched out. Our theoretical-methodological proposal consists of the definition of an integrated protocol of psycho-biological assessment and intervention on the allostatic load and on the levels of distress/eustress detectable in the sport environment, in relation to the person’s health/well-being condition and the impact of this condition on the quality of sport performance.

This paradigm has the potential to explore both the psychological dimension of stress management and the psycho-educational and psycho-physical dimension, according to a truly integrated approach to the athlete’s health and psychophysical well-being. Its multidisciplinary nature requires close cooperation between different professional figures, such as the mental coach, psychologist, nutritionist, osteopath, and physiotherapist, as well as biologists, physicians and kinesiologists, both in planning and in implementation and monitoring at all stages. The potential impact of the model on sport performance will be deeply discussed.