bluuebunny/crossref_metadata_2025 huggingface dataset:
Source identification and driving factor apportionment for soil potentially toxic elements via combining APCS-MLR, UNMIX, PMF and GDM
Authors: Gong Cang , Xia Xiang , Lan Mingguo , Shi Youchang , Lu Haichuan , Wang Shunxiang , Chen Ying
Published: May 2024

The contamination and quantification of soil potentially toxic elements (PTEs) contamination sources and the determination of driving factors are the premise of soil contamination control. In our study, 788 soil samples from the National Agricultural Park in Chengdu, Sichuan Province were used to evaluate the contamination degree of soil PTEs by pollution factors and pollution load index. The source identification of soil PTEs was performed using positive matrix decomposition (PMF), edge analysis (UNMIX) and absolute principal component score-multiple line regression (APCS-MLR). The geo-detector method (GDM) was used to analysis drivers of soil PTEs pollution sources to help interpret pollution sources derived from receptor models. Result shows that soil Cu, Pb, Zn, Cr, Ni, Cd, As and Hg average content were 35.2, 32.3, 108.9, 91.9, 37.1, 0.22, 9.76 and 0.15 mg/kg in this study area. Except for As, all are higher than the corresponding soil background values in Sichuan Province. The best performance of APCS-MLR was determined by comparison, and APCS-MLR was considered as the preferred receptor model for soil PTEs source distribution in the study area. ACPS-MLR results showed that 82.70% of Cu, 61.6% of Pb, 75.3% of Zn, 91.9% of Cr and 89.4% of Ni came from traffic-industrial emission sources, 60.9% of Hg came from domestic-transportation emission sources, 57.7% of Cd came from agricultural sources, and 89.5% of As came from natural sources. The GDM results showed that distance from first grade highway, population, land utilization and total potassium (TK) content were the main driving factors affecting these four sources, with q values of 0.064, 0.048, 0.069 and 0.058, respectively. The results can provide reference for reducing PTEs contamination in farmland soil.
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

Melatonin 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

In 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

Type 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

Very 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

Unlike 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

This 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

Cancer-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

Comprehending 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

The 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

Lack 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

Ethylenediaminetetraacetic 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

Three-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

In 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.
Chronic sensory contact with subordinated conspecifics promotes splenic glucocorticoid resistance in experimentally wounded C57BL/6N male mice
Authors: Schiele Jessica , Mazzari Giulia , Struck Antonia , Bailer Yorick , Langgartner Dominik , Reber Stefan O.
Published: May 2024

Chronic psychosocial stress induced by the chronic subordinate colony housing (CSC, 19 Days) paradigm promotes functional splenic in vitro glucocorticoid (GC) resistance, but only if associated with significant bite wounding or prior abdominal transmitter implantation. Moreover, sensory contact to social defeat of conspecifics represents a social stressor for the observer individual. As the occurence and severity of bite wounding is not adequately controllable, the present study aimed to develop an animal model, allowing a bite wound-independent, more reliable generation of chronically-stressed mice characterized by functional splenic in vitro GC resistance. Therefore, male C57BL/6N mice received a standardized sterile intraperitoneal (i.p.) incision surgery or SHAM treatment one week prior to 19-days of (i) CSC, (ii) witnessing social defeat during CSC exposure in sensory contact (SENS) or (iii) single-housing for control (SHC), before assessing basal and LPS-induced splenic in vitro cell viability and GC resistance. Our results indicate that individually-housed SENS but not CSC mice develop mild signs of splenic in vitro GC resistance, when undergoing prior i.p.-wounding. Taken together and considering that future studies are warranted, our findings support the hypothesis that the combination of repeated standardized i.p.-wounding with chronic sensory stress exposure represents an adequate tool to induce functional splenic in vitro GC resistance independent of the occurrence of uncontrollable bite wounds required in social stress paradigms to induce a comparable phenotype.
Multiple asynchronous recurrence as a predictive factor for refractoriness against locoregional and surgical therapy in patients with intermediate-stage hepatocellular carcinoma
Authors: Kasuga Ryosuke , Taniki Nobuhito , Chu Po-Sung , Tamura Masashi , Tabuchi Takaya , Yamaguchi Akihiro , Hayatsu Shigeo , Koizumi Jun , Ojiro Keisuke , Hoshi Hitomi , Kaneko Fumihiko , Morikawa Rei , Noguchi Fumie , Yamataka Karin , Usui Shingo , Ebinuma Hirotoshi , Itano Osamu , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Inoue Masanori , Nakatsuka Seishi , Jinzaki Masahiro , Kitagawa Yuko , Kanai Takanori , Nakamoto Nobuhiro
Published: May 2024

Development of subclassification of intermediate-stage hepatocellular carcinoma (HCC) by treatment suitability is in demand. We aimed to identify predictors that define treatment refractoriness against locoregional(transarterial chemoembolization(TACE) or thermal ablation) and surgical therapy. This multicenter retrospective study enrolled 1167 HCC patients between 2015 and 2021. Of those, 209 patients were initially diagnosed with intermediate-stage HCC. Treatment refractoriness was defined as clinical settings that meets the following untreatable progressive conditions by TACE (1) 25% increase of intrahepatic tumor, (2) transient deterioration to Child–Pugh class C, (3) macrovascular invasion or extrahepatic spread, within one year. We then analyzed factors contributing to treatment refractoriness. The Child–Pugh score/class, number of tumors, infiltrative radiological type, and recurrence were significant factors. Focusing on recurrence as a predictor, median time to untreatable progression (TTUP) was 17.2 months in the recurrence subgroup whereas 35.5 months in the initial occurrence subgroup (HR, 2.06; 95% CI, 1.44–2.96; P = 0.001). Median TTUP decreased in cases with more later times of recurrence (3–5 recurrences, 17.3 months; ≥ 6 recurrences, 7.7 months). Recurrence, even more at later times, leads to increased treatment refractoriness. Early introduction of multidisciplinary treatment should be considered against HCC patients after multiple recurrent episodes.
Fine-grained recognition of bitter gourd maturity based on Improved YOLOv5-seg model
Authors: Jiang Sheng , Ao Jiangbo , Yang Hualin , Xie Fangnan , Liu Ziyi , Yang Shanglin , Wei Yichen , Deng Xijin
Published: May 2024

Bitter gourd, being perishable, requires timely harvesting. Delayed harvesting can result in a substantial reduction in fruit quality. while premature harvesting leads to underdeveloped fruit and decreased yields, the continuous flowering pattern in bitter gourd underscores the significance of accurately assessing fruit growth and ensuring timely harvesting for subsequent fruit setting and development. The current reliance on the experience of production personnel represents a substantial inefficiency. We present an improved real-time instance segmentation model based on YOLOv5-seg. The utilization of dynamic snake convolution enables the extraction of morphological features from the curved and elongated structure of bitter gourd. Diverse branch blocks enhance feature space diversity without inflating model size and inference time, contributing to improved recognition of expansion stages during bitter gourd growth. Additionally, the introduction of Focal-EIOU loss accurately locates the boundary box and mask, addressing sample imbalances in the L2 stage. Experimental results showcase remarkable accuracy rates of 99.3%, 93.8%, and 98.3% for L1, L2, and L3 stages using mAP@0.5. In comparison, our model outperforms other case segmentation models, excelling in both detection accuracy and inference speed. The improved YOLOv5-seg model demonstrates strong performance in fine-grained recognition of bitter gourd during the expansion stage. It efficiently segments bitter gourd in real-time under varying lighting and occlusion conditions, providing crucial maturity information. This model offers reliable insights for agricultural workers, facilitating precise harvesting decisions.
Assessment of cardiac adverse events following COVID-19 vaccination by speckle tracking echocardiography
Authors: Chaichuum Srisakul , Tseng Ching-Li , Chang Su-Chen , Chan Chih-Lin , Hsu Chu-Ying , Chiang Edward , Daimon Masao , Chiang Shuo-Ju , Chen Hsiang-Ho
Published: May 2024

Cardiac discomfort has been reported periodically in COVID-19-vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests, electrocardiogram (ECG), and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomforts, such as chest tightness, palpitations, dyspnea, and chest pain. The ECG readings exhibited both premature ventricular contractions and premature atrial contractions (n = 24, 36.4%), while none of the individuals in the control group manifested signs of cardiac arrhythmia. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) was reduced in the symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to the control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable the evaluation of subtle changes in myocardial function after vaccination.
In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase
Authors: Shang Linyue , Wei Huimei , Deng Jing , Stewart Madeline J. , LeSaint Johnathan E. , Kyomuhangi Annet , Park Shawn , Maul Elise C. , Zhan Chang-Guo , Zheng Fang
Published: May 2024

It is recognized as a promising therapeutic strategy for cocaine use disorder to develop an efficient enzyme which can rapidly convert cocaine to physiologically inactive metabolites. We have designed and discovered a series of highly efficient cocaine hydrolases, including CocH5-Fc(M6) which is the currently known as the most efficient cocaine hydrolase with both the highest catalytic activity against (−)-cocaine and the longest biological half-life in rats. In the present study, we characterized the time courses of protein appearance, pH, structural integrity, and catalytic activity against cocaine in vitro and in vivo of a CocH5-Fc(M6) bulk drug substance produced in a bioreactor for its in vitro and in vivo stability after long-time storage under various temperatures (− 80, − 20, 4, 25, or 37 °C). Specifically, all the tested properties of the CocH5-Fc(M6) protein did not significantly change after the protein was stored at any of four temperatures including − 80, − 20, 4, and 25 °C for ~ 18 months. In comparison, at 37 °C, the protein was less stable, with a half-life of ~ 82 days for cocaine hydrolysis activity. Additionally, the in vivo studies further confirmed the linear elimination PK profile of CocH5-Fc(M6) with an elimination half-life of ~ 9 days. All the in vitro and in vivo data on the efficacy and stability of CocH5-Fc(M6) have consistently demonstrated that CocH5-Fc(M6) has the desired in vitro and in vivo stability as a promising therapeutic candidate for treatment of cocaine use disorder.
Study on the fracture propagation of ground fissures with syn-depositional structure in Fenwei Basin, China
Authors: Lu Quanzhong , Li Cong , Liu Rendao , Sun Yuemin , Mao Xinyu , Chen Feilong
Published: May 2024

In Fenwei Basin, most of the tectonic ground fissures show characteristics of growth faults on the section. They continue to destroy the engineering properties of soil at different depths. This has introduced significant security risks to the construction processes of deep underground spaces. However, there are few studies have been conducted on syn-depositional ground fissures. Therefore, in this study, a physical simulation test was used to study the fracture propagation of syn-depositional ground fissures. The characteristics of sections and surface fractures were analyzed. The engineering properties of model soil were divided into bad and poor areas. The syn-depositional ground fissure fracture propagation process was divided into five phases. The results show that soil profile exhibited a composite Y-shaped fracture morphology. Syn-deposition affects the fracture angle and healing state of fractures. The soil strain and surface displacement were positively correlated with the number of deposition layers. The conclusions of this study provide a theoretical geological basis and practical engineering significance for design of deep underground space structures.
Exploring optimal drug targets through subtractive proteomics analysis and pangenomic insights for tailored drug design in tuberculosis
Authors: Khan Muhammad Fayaz , Ali Amjad , Rehman Hafiz Muzzammel , Noor Khan Sadiq , Hammad Hafiz Muhammad , Waseem Maaz , Wu Yurong , Clark Taane G. , Jabbar Abdul
Published: May 2024

Tuberculosis (TB), caused by Mycobacterium tuberculosis, ranks among the top causes of global human mortality, as reported by the World Health Organization’s 2022 TB report. The prevalence of M. tuberculosis strains that are multiple and extensive-drug resistant represents a significant barrier to TB eradication. Fortunately, having many completely sequenced M. tuberculosis genomes available has made it possible to investigate the species pangenome, conduct a pan-phylogenetic investigation, and find potential new drug targets. The 442 complete genome dataset was used to estimate the pangenome of M. tuberculosis. This study involved phylogenomic classification and in-depth analyses. Sequential filters were applied to the conserved core genome containing 2754 proteins. These filters assessed non-human homology, virulence, essentiality, physiochemical properties, and pathway analysis. Through these intensive filtering approaches, promising broad-spectrum therapeutic targets were identified. These targets were docked with FDA-approved compounds readily available on the ZINC database. Selected highly ranked ligands with inhibitory potential include dihydroergotamine and abiraterone acetate. The effectiveness of the ligands has been supported by molecular dynamics simulation of the ligand–protein complexes, instilling optimism that the identified lead compounds may serve as a robust basis for the development of safe and efficient drugs for TB treatment, subject to further lead optimization and subsequent experimental validation.
Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson’s disease progression
Authors: Fröhlich Alexander , Pfaff Abigail L. , Middlehurst Ben , Hughes Lauren S. , Bubb Vivien J. , Quinn John P. , Koks Sulev
Published: May 2024

SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson’s disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson’s progression markers initiative cohort. We further show that SVA_67 is polymorphic for its variable number tandem repeat domain which correlates with both regulatory properties in a luciferase reporter gene assay in vitro and differential expression of multiple genes in vivo. Additionally, this variation’s utility as a biomarker is reflected in a correlation with a number of PD progression markers. These experiments highlight the plethora of transcriptomic and phenotypic changes associated with SVA_67 polymorphism which should be considered when investigating the missing heritability of neurodegenerative diseases.
Fever lasting 48 hours as a predictive factor of ESBL-producing bacteria in non-critically ill patients with urinary tract infection
Authors: Yoon Sungbin , Kim Hae-rim , Kim So Won , Yu Hoon
Published: May 2024

Urinary tract infection (UTI) is the most prevalent urological condition worldwide. Choosing appropriate antibiotics for patients who have fever before receiving a culture result is challenging. This retrospective study enrolled patients 394 patients hospitalized at Gangneung Asan Hospital for UTI from May 2017 to April 2021. Fever at 48 h of hospitalization was the analysis point, as this is when the response to antibiotic therapy manifest, although the results of antibiogram are not available. Multivariate analysis was performed to assess the correlation between ESBL producing bacteria (EPB) and fever at 48 h. Overall, 36.3% of patients had EPB and 27.9% had fever at 48 h. In multivariate analysis, a significant positive association was found between EPB and fever (odds ratio 1.17, 95% CI 1.05–1.30, P = 0.004) Female had negative association with multivariate model (OR 0.83, 95% CI 0.73–0.94, P = 0.004). Diabetes did not demonstrate a significant association with EPB. (OR 1.10, 95% CI 0.99–1.22, P = 0.072). Fever at 48 h is associated with EPB and could be considered a predictive factor for EPB infection in patients with UTI. Antibiotic escalation may be considered in patients with fever at 48 h.
A novel coupled rainfall prediction model based on stepwise decomposition technique
Authors: Jiao Xueran , He Zongheng
Published: May 2024

The traditional decomposed ensemble prediction model decomposes the entire rainfall sequence into several sub-sequences, dividing them into training and testing periods for modeling. During sample construction, future information is erroneously mixed into the training data, making it challenging to apply in practical rainfall forecasting. This paper proposes a novel stepwise decomposed ensemble coupling model, realized through variational mode decomposition (VMD) and bidirectional long short-term memory neural network (BiLSTM) models. Model parameters are optimized using an improved particle swarm optimization (IPSO). The performance of the model was evaluated using rainfall data from the Southern Four Lakes basin. The results indicate that: (1) Compared to the PSO algorithm, the IPSO algorithm-coupled model shows a minimum decrease of 2.70% in MAE and at least 2.62% in RMSE across the four cities in the Southern Four Lakes basin; the IPSO algorithm results in a minimum decrease of 25.58% in MAE and at least 28.19% in RMSE for the VMD-BiLSTM model. (2) When compared to IPSO-BiLSTM, the VMD-IPSO-BiLSTM based on the stepwise decomposition technique exhibits a minimum decrease of 26.54% in MAE and at least 34.16% in RMSE. (3) The NSE for the testing period of the VMD-IPSO-BiLSTM model in each city surpasses 0.88, indicating higher prediction accuracy and providing new insights for optimizing rainfall forecasting.
Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis
Authors: Li Zi-Jing , Pat Fong William , Zhang Dong-Sheng , Luo Hui-Yan , Chen Dong-Liang , Cai Yan-Yu , Chen Zhi-Gang , Duan Jian-Li , Huang Zi-Yao , Lu Yu-Ting , Huang Xiao-Xia , Li Yu-Hong , Wang De-Shen
Published: May 2024

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.
FDA-cleared home sleep apnea testing devices
Authors: Park Ji Hyeun , Wang Changwon , Shin Hangsik
Published: May 2024

The demand for home sleep apnea testing (HSAT) devices is escalating, particularly in the context of the coronavirus 2019 (COVID-19) pandemic. The absence of standardized development and verification procedures poses a significant challenge. This study meticulously analyzed the approval process characteristics of HSAT devices by the U.S. Food and Drug Administration (FDA) from September 1, 2003, to September 1, 2023, with a primary focus on ensuring safety and clinical effectiveness. We examined 58 reports out of 1046 that underwent FDA clearance via the 510(k) and de novo pathways. A substantial surge in certifications after the 2022 pandemic was observed. Type-3 devices dominated, signifying a growing trend for both home and clinical use. Key measurement items included respiration and sleep analysis, with the apnea–hypopnea index (AHI) and sleep stage emerging as pivotal indicators. The majority of FDA-cleared HSAT devices adhered to electrical safety and biocompatibility standards. Critical considerations encompass performance and function testing, usability, and cybersecurity. This study emphasized the nearly indispensable role of clinical trials in ensuring the clinical effectiveness of HSAT devices. Future studies should propose guidances that specify stringent requirements, robust clinical trial designs, and comprehensive performance criteria to guarantee the minimum safety and clinical effectiveness of HSATs.
Acoustic-based approach for micro-leakage detection and localization in water supply pipelines
Authors: Feng Cuimin , Zhao Jiancong , Ran Qiangsan , Qu Mengchao , Guo Zixiao
Published: May 2024

Improving the accuracy of acoustic detection techniques is crucial, especially in scenarios with low pipeline pressures (≤0.2 MPa) and small leak apertures (≤2 mm), where micro-leakage detection poses challenges.
Dual modulation of blue-fluorescent carbon dots for simultaneous detection of topotecan and pantoprazole
Authors: Mahmoud Ashraf M. , Alqahtani Yahya S. , El-Wekil Mohamed M. , Bellah H. Ali Al-Montaser
Published: May 2024

Simultaneous determination of topotecan and pantoprazole.
Ruthenium catalyzed dehydrogenative α-C–H functionalization of β-naphthol using alcohols: a metal–ligand cooperative borrowing hydrogen approach
Authors: Guin Amit Kumar , Chakraborty Santana , Khanra Subhankar , Mohapatra Arijit Singha , Paul Nanda D.
Published: May 2024

Chemoselective α-C–H functionalization of β-naphthol is achieved with inexpensive and readily available alcohols using a well-defined, air-stable, and easy-to-prepare Ru(ii)-catalyst (1a) bearing a redox-active tridentate pincer (L1a).
Enhanced gas sensing performance of sprayed ZnO–ZnWO4 toward CO gas
Authors: Sayed Mohamed H. , Dilova Tina , Atanasova Genoveva , Avdeev Georgi , Boshta Mostafa , Dikovska Anna Og. , Gomaa Mohammed M.
Published: May 2024

The sprayed ZnO–ZnWO4 composite shows a maximum sensitivity of 422.7% for 30 ppm CO with good sensor performance. The sprayed ZnO–ZnWO4 composite layer is a good candidate material for CO detection at a relatively low operating temperature.
Band gap engineering in pyridyl-functionalized two-dimensional (2D) CuSCN coordination polymers
Authors: Songkerdthong Jetnipat , Thanasarnsurapong Thanasee , Boonchun Adisak , Harding David J. , Pattanasattayavong Pichaya
Published: May 2024

3D CuSCN is transformed into 2D sheet structures when coordinated with pyridine (Py)-based ligands at a specific 1 : 1 ratio. By varying the substituent at the 3-position, the optical and electronic properties can be systematically tuned.
Catalyst-free multicomponent polymerization of aldehydes, amines and trimethylsilyl cyanide toward poly(α-aminonitrile)s
Authors: Cheng Tianyu , Wang Huadong , Ding Jianqing , Fang Junguo , Wang Jia , Li Mingzhao , Chen Jie , Qin Anjun , Tang Ben Zhong
Published: May 2024

An effecient multicomponent polymerization of dialdehydes, diamines and trimethylsilyl cyanide for preparation of cyano-containing polymers poly(α-aminonitrile)s was established. And the properties of poly(α-aminonitrile)s were investigated.
Convergence criteria for single-step free-energy calculations: the relation between the Π bias measure and the sample variance
Authors: Wang Meiting , Mei Ye , Ryde Ulf
Published: May 2024

We study convergence of single-step exponential averaging and how it depends on the standard deviation of the energy difference and Kofke's bias measure Π. We suggest a practical procedure to decide the sample size to obtain converged free energies.
Duplex-forming oligocarbamates with tunable nonbonding sites
Authors: Weigel R. Kenton , Alabi Christopher A.
Published: May 2024

Sequence-defined oligocarbamates with thymine and diaminotriazine pendant groups assemble into duplexes. The binding strength (Ka), enthalpy (ΔH), and entropy (ΔS) of hybridization depend on the valency and sequence of the interacting ligands.
Conformational flexibility driving charge-selective substrate translocation across a bacterial transporter
Authors: Vikraman Devika , Majumdar Bibhab Bandhu , SK Sharavanakkumar , Weichbrodt Conrad , Fertig Niels , Winterhalter Mathias , Mondal Jagannath , Mahendran Kozhinjampara R.
Published: May 2024

Here, we establish the conformational dynamics of a specialized natural passive bacterial transporter, CymA, using single-channel recordings and molecular dynamics simulations.