bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantum mechanics insights into melatonin and analogs binding to melatonin MT1 and MT2 receptors
Authors: de Lima Menezes Gabriela , Sales Bezerra Katyanna , Nobre Oliveira Jonas Ivan , Fontenele Araújo John , Soares Galvão Douglas , Alves da Silva Roosevelt , Vogel Saivish Marielena , Laino Fulco Umberto 
Published: May 2024

AbstractMelatonin receptors MT1 and MT2 are G protein-coupled receptors that mediate the effects of melatonin, a hormone involved in circadian rhythms and other physiological functions. Understanding the molecular interactions between these receptors and their ligands is crucial for developing novel therapeutic agents. In this study, we used molecular docking, molecular dynamics simulations, and quantum mechanics calculation to investigate the binding modes and affinities of three ligands: melatonin (MLT), ramelteon (RMT), and 2-phenylmelatonin (2-PMT) with both receptors. Based on the results, we identified key amino acids that contributed to the receptor-ligand interactions, such as Gln181/194, Phe179/192, and Asn162/175, which are conserved in both receptors. Additionally, we described new meaningful interactions with Gly108/Gly121, Val111/Val124, and Val191/Val204. Our results provide insights into receptor-ligand recognition’s structural and energetic determinants and suggest potential strategies for designing more optimized molecules. This study enhances our understanding of receptor-ligand interactions and offers implications for future drug development.
Multiplex PCR for bacterial, viral and protozoal pathogens in persistent diarrhoea or persistent abdominal pain in Côte d’Ivoire, Mali and Nepal
Authors: Jasuja Jasmin K. , Bub Florian , Veit Jonas , Fofana Hassan K. M. , Sacko Moussa , Saye Rénion , Chatigre Justin K. , N’Goran Eliézer K. , Yao Joel A. , Khanal Basudha , Koirala Kanika , Bhattarai Narayan R. , Rijal Suman , von Müller Lutz , Bottieau Emmanuel , Boelaert Marleen , Chappuis François , Polman Katja , Utzinger Jürg , Becker Sören L. 
Published: May 2024

AbstractIn contrast to acute diarrhoea, the aetiology of persistent digestive disorders (≥ 14 days) is poorly understood in low-resource settings and conventional diagnostic approaches lack accuracy. In this multi-country study, we compared multiplex real-time PCR for enteric bacterial, parasitic and viral pathogens in stool samples from symptomatic patients and matched asymptomatic controls in Côte d’Ivoire, Mali and Nepal. Among 1826 stool samples, the prevalence of most pathogens was highest in Mali, being up to threefold higher than in Côte d’Ivoire and up to tenfold higher than in Nepal. In all settings, the most prevalent bacteria were EAEC (13.0–39.9%) and Campylobacter spp. (3.9–35.3%). Giardia intestinalis was the predominant intestinal protozoon (2.9–20.5%), and adenovirus 40/41 was the most frequently observed viral pathogen (6.3–25.1%). Significantly different prevalences between symptomatic and asymptomatic individuals were observed for Campylobacter, EIEC and ETEC in the two African sites, and for norovirus in Nepal. Multiple species pathogen infection was common in Côte d’Ivoire and Mali, but rarely found in Nepal. We observed that molecular testing detected multiple enteric pathogens and showed low discriminatory accuracy to distinguish between symptomatic and asymptomatic individuals. Yet, multiplex PCR allowed for direct comparison between different countries and revealed considerable setting-specificity.
P2X7R and P2X4R expression of mice submandibular gland in high-fat diet/streptozotocin-induced type 2 diabetes
Authors: Srisutha Jiratchaya , Watari Ippei , Akakura Masato , Watanabe Minami , Changsiripun Chidsanu , Ono Takashi 
Published: May 2024

AbstractType 2 diabetes mellitus (T2DM) is a chronic inflammatory disease that can compromise the functioning of various organs, including the salivary glands (SG). The purinergic system is one of the most important inflammatory pathways in T2DM condition, and P2X7R and P2X4R are the primary purinergic receptors in SG that regulate inflammatory homeostasis. This study aimed to evaluate P2X7R and P2X4R expression, and morphological changes in the submandibular gland (SMG) in T2DM. Twenty-four 5-week-old mice were randomly assigned to control (CON) and diabetes mellitus (DM) groups (n = 12 each). Body weight, diet, and blood glucose levels were monitored weekly. The histomorphology of the SMG and the expression of the P2X7R, and P2X7R was evaluated by immunohistochemistry (IHC) staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) at 11 and 13 weeks of age. Our findings indicate a significant increase in food consumption, body weight, and blood glucose levels in the DM group. Although a significant increase in P2X7R and P2X4R expression was observed in the DM groups, the receptor location remained unchanged. We also observed a significant increase in the acinar area in the DM13w group, and a significant decrease in the ductal area in the DM11w and DM13w groups. Targeting purinergic receptors may offer novel therapeutic methods for diabetic complications.
First in vitro measurement of VHEE relative biological effectiveness (RBE) in lung and prostate cancer cells using the ARES linac at DESY
Authors: Wanstall Hannah C. , Burkart Florian , Dinter Hannes , Kellermeier Max , Kuropka Willi , Mayet Frank , Vinatier Thomas , Santina Elham , Chadwick Amy L. , Merchant Michael J. , Henthorn Nicholas T. , Köpke Michael , Stacey Blae , Jaster-Merz Sonja , Jones Roger M. 
Published: May 2024

AbstractVery high energy electrons (VHEE) are a potential candidate for radiotherapy applications. This includes tumours in inhomogeneous regions such as lung and prostate cancers, due to the insensitivity of VHEE to inhomogeneities. This study explores how electrons in the VHEE range can be used to perform successful in vitro radiobiological studies. The ARES (accelerator research experiment at SINBAD) facility at DESY, Hamburg, Germany was used to deliver 154 MeV electrons to both prostate (PC3) and lung (A549) cancer cells in suspension. Dose was delivered to samples with repeatability and uniformity, quantified with Gafchromic film. Cell survival in response to VHEE was measured using the clonogenic assay to determine the biological effectiveness of VHEE in cancer cells for the first time using this method. Equivalent experiments were performed using 300 kVp X-rays, to enable VHEE irradiated cells to be compared with conventional photons. VHEE irradiated cancer cell survival was fitted to the linear quadratic (LQ) model (R2 = 0.96–0.97). The damage from VHEE and X-ray irradiated cells at doses between 1.41 and 6.33 Gy are comparable, suggesting similar relative biological effectiveness (RBE) between the two modalities. This suggests VHEE is as damaging as photon radiotherapy and therefore could be used to successfully damage cancer cells during radiotherapy. The RBE of VHEE was quantified as the relative doses required for 50% (D0.5) and 10% (D0.1) cell survival. Using these values, VHEE RBE was measured as 0.93 (D0.5) and 0.99 (D0.1) for A549 and 0.74 (D0.5) and 0.93 (D0.1) for PC3 cell lines respectively. For the first time, this study has shown that 154 MeV electrons can be used to effectively kill lung and prostate cancer cells, suggesting that VHEE would be a viable radiotherapy modality. Several studies have shown that VHEE has characteristics that would offer significant improvements over conventional photon radiotherapy for example, electrons are relatively easy to steer and can be used to deliver dose rapidly and with high efficiency. Studies have shown improved dose distribution with VHEE in treatment plans, in comparison to VMAT, indicating that VHEE can offer improved and safer treatment plans with reduced side effects. The biological response of cancer cells to VHEE has not been sufficiently studied as of yet, however this initial study provides some initial insights into cell damage. VHEE offers significant benefits over photon radiotherapy and therefore more studies are required to fully understand the biological effectiveness of VHEE.
Twist2 contributes to skin regeneration and hair follicle formation in mouse fetuses
Authors: Takaya Kento , Sunohara Ayano , Sakai Shigeki , Aramaki-Hattori Noriko , Okabe Keisuke , Kishi Kazuo 
Published: May 2024

AbstractUnlike adult mammalian wounds, early embryonic mouse skin wounds completely regenerate and heal without scars. Analysis of the underlying molecular mechanism will provide insights into scarless wound healing. Twist2 is an important regulator of hair follicle formation and biological patterning; however, it is unclear whether it plays a role in skin or skin appendage regeneration. Here, we aimed to elucidate Twist2 expression and its role in fetal wound healing. ICR mouse fetuses were surgically wounded on embryonic day 13 (E13), E15, and E17, and Twist2 expression in tissue samples from these fetuses was evaluated via in situ hybridization, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction. Twist2 expression was upregulated in the dermis of E13 wound margins but downregulated in E15 and E17 wounds. Twist2 knockdown on E13 left visible marks at the wound site, inhibited regeneration, and resulted in defective follicle formation. Twist2-knockdown dermal fibroblasts lacked the ability to undifferentiate. Furthermore, Twist2 hetero knockout mice (Twist + /-) formed visible scars, even on E13, when all skin structures should regenerate. Thus, Twist2 expression correlated with skin texture formation and hair follicle defects in late mouse embryos. These findings may help develop a therapeutic strategy to reduce scarring and promote hair follicle regeneration.
Medicolegal analysis of physical violence toward physicians in Egypt
Authors: Khedr Rasha Ismail , Mohamed Omneya Ibrahim , Sobh Zahraa Khalifa 
Published: May 2024

AbstractThis study analyzed physical violence against physicians in Egypt from a medicolegal perspective. 88%, 42%, and 13.2% of participants were exposed to verbal, physical, and sexual violence. Concerning the tools of violence, 75.2% of attackers used their bodies. Blunt objects (29.5%), sharp instruments (7.6%), and firearm weapons (1.9%) were used. The commonest manners of attacks were pushing/pulling (44.8%), throwing objects (38.1%), and fists (30.5%). Stabbing (4.8%) and slashing (2.9%) with sharp instruments were also reported. Traumas were mainly directed towards upper limbs (43.8%), trunks (40%), and heads (28.6%). Considering immediate effects, simple injuries were reported that included contusions (22.9%), abrasions (16.2%), and cut wounds (1.9%). Serious injuries included firearm injuries (4.8%), internal organs injuries (3.8%), fractures (2.9%), and burns (1.9%). Most (90.5%) of injuries healed completely, whereas 7.6% and 1.9% left scars and residual infirmities, respectively. Only 14.3% of physicians proceeded to legal action. The current study reflects high aggression, which is disproportionate to legal actions taken by physicians. This medicolegal analysis could guide protective measures for healthcare providers in Egypt. In addition, a narrative review of studies from 15 countries pointed to violence against physicians as a worldwide problem that deserves future medicolegal analyses.
A dual model of normal vs isogenic Nrf2-depleted murine epithelial cells to explore oxidative stress involvement
Authors: Dupuy Jacques , Fouché Edwin , Noirot Céline , Martin Pierre , Buisson Charline , Guéraud Françoise , Pierre Fabrice , Héliès-Toussaint Cécile 
Published: May 2024

AbstractCancer-derived cell lines are useful tools for studying cellular metabolism and xenobiotic toxicity, but they are not suitable for modeling the biological effects of food contaminants or natural biomolecules on healthy colonic epithelial cells in a normal genetic context. The toxicological properties of such compounds may rely on their oxidative properties. Therefore, it appears to be necessary to develop a dual-cell model in a normal genetic context that allows to define the importance of oxidative stress in the observed toxicity. Given that the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered to be the master regulator of antioxidant defenses, our aim was to develop a cellular model comparing normal and Nrf2-depleted isogenic cells to qualify oxidative stress–related toxicity. We generated these cells by using the CRISPR/Cas9 technique. Whole-genome sequencing enabled us to confirm that our cell lines were free of cancer-related mutations. We used 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product closely related to oxidative stress, as a model molecule. Here we report significant differences between the two cell lines in glutathione levels, gene regulation, and cell viability after HNE treatment. The results support the ability of our dual-cell model to study the role of oxidative stress in xenobiotic toxicity.
Analyzing factors causing deadlock events of bi-directional pedestrian flow when moving on stairs using a personal space model
Authors: Liu Mingwei , Lu Guiliang , Yoshinao Oeda 
Published: May 2024

AbstractComprehending crowd dynamics on staircases is imperative for preventing accidents, particularly in emergency scenarios. In this context, our study delves into bi-directional pedestrian flow. When confronted with limited staircase space, the occurrence of two distinct lanes—one for upstairs and another for downstairs—is a common observation. However, there has been no quantitative investigation conducted to understand this phenomenon. To facilitate such an analysis, we employ a velocity-based personal space model that accurately reproduces the formation of upstairs and downstairs lanes in bi-directional staircases. The study of lane formation mechanisms and the exploration of factors influencing deadlock are essentially two sides of the same coin. This is due to the fact that, the occurrence of deadlock signifies a disruption in the anticipated lane behavior during counter flow. As a result, we have devised various scenarios to meticulously analyze the factors contributing to both deadlock formation and its subsequent performance. This involves manipulating parameters such as speed, speed dispersion, pedestrian count, initial density, right-hand preference weight, minimum personal space size, same-direction following intensity, and time step. The findings hold the potential to enhance the overall quality of service in stairway movement and offer significant contributions to the understanding and management of pedestrian behavior in such settings.
Vegetable omega-3 and omega-6 fatty acids differentially modulate the antiviral and antibacterial immune responses of Atlantic salmon
Authors: Caballero-Solares Albert , Eslamloo Khalil , Hall Jennifer R. , Katan Tomer , Emam Mohamed , Xue Xi , Taylor Richard G. , Balder Rachel , Parrish Christopher C. , Rise Matthew L. 
Published: May 2024

AbstractThe immunomodulatory effects of omega-3 and omega-6 fatty acids are a crucial subject of investigation for sustainable fish aquaculture, as fish oil is increasingly replaced by terrestrial vegetable oils in aquafeeds. Unlike previous research focusing on fish oil replacement with vegetable alternatives, our study explored how the omega-6 to omega-3 polyunsaturated fatty acid (PUFA) ratio in low-fish oil aquafeeds influences Atlantic salmon's antiviral and antibacterial immune responses. Atlantic salmon were fed aquafeeds rich in soy oil (high in omega-6) or linseed oil (high in omega-3) for 12 weeks and then challenged with bacterial (formalin-killed Aeromonas salmonicida) or viral-like (polyriboinosinic polyribocytidylic acid) antigens. The head kidneys of salmon fed high dietary omega-3 levels exhibited a more anti-inflammatory fatty acid profile and a restrained induction of pro-inflammatory and neutrophil-related genes during the immune challenges. The high-omega-3 diet also promoted a higher expression of genes associated with the interferon-mediated signaling pathway, potentially enhancing antiviral immunity. This research highlights the capacity of vegetable oils with different omega-6 to omega-3 PUFA ratios to modulate specific components of fish immune responses, offering insights for future research on the intricate lipid nutrition-immunity interplay and the development of novel sustainable low-fish oil clinical aquaculture feeds.
Vaccine hesitancy and trust in sub-Saharan Africa
Authors: Unfried Kerstin , Priebe Jan 
Published: May 2024

AbstractLack of trust is a primary reason behind the global rise in vaccine hesitancy. Existing research on the trust—vaccine hesitancy nexus has almost exclusively focused on COVID-19 with the vast majority of studies examining industrialized countries. In this study, we investigated the influence of trust in different policy-relevant actors (government, science, media, pharmaceutical companies, society) on vaccine hesitancy for recently available vaccines related to polio and HPV which we benchmark against a COVID-19 vaccine. Leveraging unique primary data on 5203 individuals from six countries (Ghana, Kenya, Nigeria, South Africa, Tanzania, and Uganda), we showed that individuals’ trust in the government and society are key predictors of vaccine hesitancy. Furthermore, we demonstrated that these relationships are remarkably stable across vaccine, disease, and country contexts.
Hypertonic saline- and detergent-accelerated EDTA-based decalcification better preserves mRNA of bones
Authors: Li Zhongmin , Wenhart Clara , Reimann Andreas , Cho Yi-Li , Adler Kristin , Muench Goetz 
Published: May 2024

AbstractEthylenediaminetetraacetic acid (EDTA), a classically used chelating agent of decalcification, maintains good morphological details, but its slow decalcification limits its wider applications. Many procedures have been reported to accelerate EDTA-based decalcification, involving temperature, concentration, sonication, agitation, vacuum, microwave, or combination. However, these procedures, concentrating on purely tissue-outside physical factors to increase the chemical diffusion, do not enable EDTA to exert its full capacity due to tissue intrinsic chemical resistances around the diffusion passage. The resistances, such as tissue inner lipids and electric charges, impede the penetration of EDTA. We hypothesized that delipidation and shielding electric charges would accelerate EDTA-based penetration and the subsequent decalcification. The hypothesis was verified by the observation of speedy penetration of EDTA with additives of detergents and hypertonic saline, testing on tissue-mimicking gels of collagen and adult mouse bones. Using a 26% EDTA mixture with the additives at 45°C, a conventional 7-day decalcification of adult mouse ankle joints could be completed within 24 h while the tissue morphological structure, antigenicity, enzymes, and DNA were well preserved, and mRNA better retained compared to using 15% EDTA at room temperature. The addition of hypertonic saline and detergents to EDTA decalcification is a simple, rapid, and inexpensive method that doesn't disrupt the current histological workflow. This method is equally or even more effective than the currently most used decalcification methods in preserving the morphological details of tissues. It can be highly beneficial for the related community.
Revealing the complexity of meniscus microvasculature through 3D visualization and analysis
Authors: Orellana Federica , Grassi Alberto , Hlushchuk Ruslan , Wahl Peter , Nuss Katja M. , Neels Antonia , Zaffagnini Stefano , Parrilli Annapaola 
Published: May 2024

AbstractThree-dimensional information is essential for a proper understanding of the healing potential of the menisci and their overall role in the knee joint. However, to date, the study of meniscal vascularity has relied primarily on two-dimensional imaging techniques. Here we present a method to elucidate the intricate 3D meniscal vascular network, revealing its spatial arrangement, connectivity and density. A polymerizing contrast agent was injected into the femoral artery of human cadaver legs, and the meniscal microvasculature was examined using micro-computed tomography at different levels of detail and resolution. The 3D vascular network was quantitatively assessed in a zone-base analysis using parameters such as diameter, length, tortuosity, and branching patterns. The results of this study revealed distinct vascular patterns within the meniscus, with the highest vascular volume found in the outer perimeniscal zone. Variations in vascular parameters were found between the different circumferential and radial meniscal zones. Moreover, through state-of-the-art 3D visualization using micro-CT, this study highlighted the importance of spatial resolution in accurately characterizing the vascular network. These findings, both from this study and from future research using this technique, improve our understanding of microvascular distribution, which may lead to improved therapeutic strategies.
Evaluation of pretreatment methods for filamentous fungal detection
Authors: Jiang Xiaoli , Xiao Daiwen , Yu Hua , Sun Anhua , Liu Qin , Liu Tao 
Published: May 2024

AbstractIn order to obtain the best mass spectrometry identification results for using the most appropriate methods in clinical practice, we explore the optimal pretreatment methods for different species and morphologies of filamentous fungi. 98 fungal strains were treated with formic acid sandwich method, dispersion method, extraction method, and other methods using a medium element mass spectrometer (EXS3000) as a platform. Each strain had three targets, and the identification rates and confidence differences under different pre-treatment methods were compared to evaluate the identification effects of these methods. The mass spectrometry identification rates of 98 filamentous fungi obtained after pre-treatment with formic acid sandwich method, dispersion method, and extraction method were 85.71%, 82.65%, and 75.51%, respectively. The identification rate of the formic acid sandwich method was significantly higher than the other two methods (P < 0 005) has the best identification ability and the obtained confidence is also higher than the other two methods. The use of formic acid sandwich method for mass spectrometry identification of filamentous fungi can achieve ideal identification results, which is suitable for mass spectrometry identification of filamentous fungi in conventional laboratories.