bluuebunny/crossref_metadata_2025 huggingface dataset:
Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer’s disease
Authors: Xiong Wei , Liu Ye , Zhou Heng , Li Junyi , Jing Shuili , Jiang Cailei , Li Mei , He Yan , Ye Qingsong
Published: May 2024

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer’s disease (AD), particularly in the early stages of the disease. The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases. We herein demonstrated that human dental pulp stem cells (hDPSCs) mediated oxidative stress improvement and neuroreparative effects in in vitro AD models, playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons. Importantly, these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs, with the treated mice showing significant improvement in cognitive function and neuropathological features. Mechanistically, antioxidant and neuroprotective effects, as well as cognitive enhancements elicited by hDPSCs, were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway. In conclusion, our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models, which may be a tremendous potential therapeutic candidate for Alzheimer’s disease.
Integrated proteogenomic analysis for inherited bone marrow failure syndrome
Authors: Wakamatsu Manabu , Muramatsu Hideki , Sato Hironori , Ishikawa Masaki , Konno Ryo , Nakajima Daisuke , Hamada Motoharu , Okuno Yusuke , Kawashima Yusuke , Hama Asahito , Ito Masafumi , Iwafuchi Hideto , Takahashi Yoshiyuki , Ohara Osamu
Published: May 2024

Recent advances in in-depth data-independent acquisition proteomic analysis have enabled comprehensive quantitative analysis of >10,000 proteins. Herein, an integrated proteogenomic analysis for inherited bone marrow failure syndrome (IBMFS) was performed to reveal their biological features and to develop a proteomic-based diagnostic assay in the discovery cohort; dyskeratosis congenita (n = 12), Fanconi anemia (n = 11), Diamond–Blackfan anemia (DBA, n = 9), Shwachman–Diamond syndrome (SDS, n = 6), ADH5/ALDH2 deficiency (n = 4), and other IBMFS (n = 18). Unsupervised proteomic clustering identified eight independent clusters (C1–C8), with the ribosomal pathway specifically downregulated in C1 and C2, enriched for DBA and SDS, respectively. Six patients with SDS had significantly decreased SBDS protein expression, with two of these not diagnosed by DNA sequencing alone. Four patients with ADH5/ALDH2 deficiency showed significantly reduced ADH5 protein expression. To perform a large-scale rapid IBMFS screening, targeted proteomic analysis was performed on 417 samples from patients with IBMFS-related hematological disorders (n = 390) and healthy controls (n = 27). SBDS and ADH5 protein expressions were significantly reduced in SDS and ADH5/ALDH2 deficiency, respectively. The clinical application of this first integrated proteogenomic analysis would be useful for the diagnosis and screening of IBMFS, where appropriate clinical screening tests are lacking.
Early life stress is associated with greater negative emotionality and peripheral inflammation in alcohol use disorder
Authors: Kirsch Dylan E. , Grodin Erica N. , Nieto Steven J. , Kady Annabel , Ray Lara A.
Published: May 2024

Early life stress (ELS) increases risk for psychiatric illness, including alcohol use disorder (AUD). Researchers have hypothesized that individuals with and without a history of ELS who have the same primary DSM-5 diagnosis are clinically and biologically distinct. While there is strong support for this hypothesis in the context of mood disorders, the hypothesis remains largely untested in the context of AUD. This study investigated the impact of ELS on the neuroclinical phenomenology and inflammatory profile of individuals with AUD. Treatment-seeking adults with AUD (N = 163) completed the Adverse Childhood Experiences (ACE) Questionnaire and phenotypic battery as part of a pharmacotherapy trial for AUD (NCT03594435). Participants were classified as having “no-ELS,” (ACE = 0) “moderate-ELS,” (ACE = 1, 2 or 3) or “high-ELS” (ACE = 4 + ). The Addictions Neuroclinical Assessment domains incentive salience and negative emotionality were derived and used to assess the neuroclinical phenomenology of AUD. We tested (1) cumulative ELS as a predictor of ANA domains and (2) ELS group differences in ANA domains. A subset of participants (N = 98) provided blood samples for a biomarker of peripheral inflammation (C-reactive protein; CRP); analyses were repeated with CRP as the outcome variable. Greater ELS predicted higher negative emotionality and elevated CRP, but not incentive salience. The high-ELS group exhibited greater negative emotionality compared with the no-ELS and moderate-ELS groups, with no difference between the latter two groups. The high-ELS group exhibited elevated CRP compared with the no/moderate-ELS group. Findings suggest that high-ELS exposure is associated with a unique AUD neuroclinical presentation marked by greater negative emotionality, and inflammatory profile characterized by elevated peripheral CRP.
Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study
Authors: Liu Hong-Hong , Xie Yunbo , Yang Bao-Peng , Wen Huan-Yue , Yang Peng-Hui , Lu Jin-E , Liu Yan , Chen Xi , Qu Meng-Meng , Zhang Yang , Hong Wei-Guo , Li Yong-Gang , Fu Junliang , Wang Fu-Sheng
Published: May 2024

The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.
Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway
Authors: Støer Nathalie C. , Vangen Siri , Singh Deependra , Fortner Renée T. , Hofvind Solveig , Ursin Giske , Botteri Edoardo
Published: May 2024

Background

It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs.

Methods

We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference.

Results

We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31–2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35–1.96) to Kliogest®: 2.67 (2.37–3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86–2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83–2.30) than screen-detected (HR 1.33, 95% CI 1.26–1.41) BC in women 50–71 years. HRs for HT use decreased with increasing BMI.

Conclusions

The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.
Renal macrophages and NLRP3 inflammasomes in kidney diseases and therapeutics
Authors: Islamuddin Mohammad , Qin Xuebin
Published: May 2024

Macrophages are exceptionally diversified cell types and perform unique features and functions when exposed to different stimuli within the specific microenvironment of various kidney diseases. In instances of kidney tissue necrosis or infection, specific patterns associated with damage or pathogens prompt the development of pro-inflammatory macrophages (M1). These M1 macrophages contribute to exacerbating tissue damage, inflammation, and eventual fibrosis. Conversely, anti-inflammatory macrophages (M2) arise in the same circumstances, contributing to kidney repair and regeneration processes. Impaired tissue repair causes fibrosis, and hence macrophages play a protective and pathogenic role. In response to harmful stimuli within the body, inflammasomes, complex assemblies of multiple proteins, assume a pivotal function in innate immunity. The initiation of inflammasomes triggers the activation of caspase 1, which in turn facilitates the maturation of cytokines, inflammation, and cell death. Macrophages in the kidneys possess the complete elements of the NLRP3 inflammasome, including NLRP3, ASC, and pro-caspase-1. When the NLRP3 inflammasomes are activated, it triggers the activation of caspase-1, resulting in the release of mature proinflammatory cytokines (IL)-1β and IL-18 and cleavage of Gasdermin D (GSDMD). This activation process therefore then induces pyroptosis, leading to renal inflammation, cell death, and renal dysfunction. The NLRP3–ASC–caspase-1–IL-1β–IL-18 pathway has been identified as a factor in the development of the pathophysiology of numerous kidney diseases. In this review, we explore current progress in understanding macrophage behavior concerning inflammation, injury, and fibrosis in kidneys. Emphasizing the pivotal role of activated macrophages in both the advancement and recovery phases of renal diseases, the article delves into potential strategies to modify macrophage functionality and it also discusses emerging approaches to selectively target NLRP3 inflammasomes and their signaling components within the kidney, aiming to facilitate the healing process in kidney diseases.
Microbial community structure of plant-based meat alternatives
Authors: Roch Franz-Ferdinand , Dzieciol Monika , Quijada Narciso M. , Alteio Lauren V. , Mester Patrick-Julian , Selberherr Evelyne
Published: May 2024

A reduction in animal-based diets has driven market demand for alternative meat products, currently raising a new generation of plant-based meat alternatives (PBMAs). It remains unclear whether these substitutes are a short-lived trend or become established in the long term. Over the last few years, the trend of increasing sales and diversifying product range has continued, but publication activities in this field are currently limited mainly to market research and food technology topics. As their popularity increases, questions emerge about the safety and nutritional risks of these novel products. Even though all the examined products must be heated before consumption, consumers lack experience with this type of product and thus further research into product safety, is desirable. To consider these issues, we examined 32 PBMAs from Austrian supermarkets. Based on 16S rRNA gene amplicon sequencing, the majority of the products were dominated by lactic acid bacteria (either Leuconostoc or Latilactobacillus), and generally had low alpha diversity. Pseudomonadota (like Pseudomonas and Shewanella) dominated the other part of the products. In addition to LABs, a high diversity of different Bacillus, but also some Enterobacteriaceae and potentially pathogenic species were isolated with the culturing approach. We assume that especially the dominance of heterofermentative LABs has high relevance for the product stability and quality with the potential to increase shelf life of the products. The number of isolated Enterobacteriaceae and potential pathogens were low, but they still demonstrated that these products are suitable for their presence.
Development of catalytic zero-valent iron incorporated PAN catalytic film for efficient degradation of organic matters
Authors: Yang Yi , Lin Haowen , Long Yuxi , Mei Ying , Chen J. Paul
Published: May 2024

Catalytic films work well in degradation of organic matters. However, catalytic activity and stability of films are challenging factors. A nanoscale zero-valent iron (NZVI) incorporated porous PAN fiber (Fe-PAN) film was thus developed through a one-step cryogenic auxiliary electrospinning method. The Fe-PAN film overcame the problem in the traditional multistep preparation process. The excellent intrinsic properties of the polymer in the film were maintained. It exhibited high catalytic activity (> 95% conversion in just 4 min) and excellent stability and reusability, due to the synergistic interaction between PAN and NZVI. The degradation process was optimized by the Box-Behnken design, leading to the optimal condition: pH = 2.8, temperature = 56 °C, and oxidant concentration = 4.2 mmol/L. The degradation followed the 2nd order kinetic equation and was due to the reactions by ·OH and O2-· radicals. This study demonstrates the great potentials of the Fe-PAN film for industrial applications.
Harnessing clonal gametes in hybrid crops to engineer polyploid genomes
Authors: Wang Yazhong , Fuentes Roven Rommel , van Rengs Willem M. J. , Effgen Sieglinde , Zaidan Mohd Waznul Adly Mohd , Franzen Rainer , Susanto Tamara , Fernandes Joiselle Blanche , Mercier Raphael , Underwood Charles J.
Published: May 2024

Heterosis boosts crop yield; however, harnessing additional progressive heterosis in polyploids is challenging for breeders. We bioengineered a ‘mitosis instead of meiosis’ (MiMe) system that generates unreduced, clonal gametes in three hybrid tomato genotypes and used it to establish polyploid genome design. Through the hybridization of MiMe hybrids, we generated ‘4-haplotype’ plants that encompassed the complete genetics of their four inbred grandparents, providing a blueprint for exploiting polyploidy in crops.
Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer
Authors: Zeng Yue , Hu Chun-Hong , Li Yi-Zheng , Zhou Jian-Song , Wang Shu-Xing , Liu Meng-Dong , Qiu Zhen-Hua , Deng Chao , Ma Fang , Xia Chun-Fang , Liang Fei , Peng Yu-Rong , Liang Ao-Xi , Shi Sheng-Hao , Yao Shi-Jiao , Liu Jun-Qi , Xiao Wen-Jie , Lin Xiao-Qiao , Tian Xin-Yu , Zhang Ying-Zhe , Tian Zhuo-Ying , Zou Ji-An , Li Yun-Shu , Xiao Chao-Yue , Xu Tian , Zhang Xiao-Jie , Wang Xiao-Ping , Liu Xian-Ling , Wu Fang
Published: May 2024

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979.
High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response
Authors: Mentzer Alexander J. , Dilthey Alexander T. , Pollard Martin , Gurdasani Deepti , Karakoc Emre , Carstensen Tommy , Muhwezi Allan , Cutland Clare , Diarra Amidou , da Silva Antunes Ricardo , Paul Sinu , Smits Gaby , Wareing Susan , Kim HwaRan , Pomilla Cristina , Chong Amanda Y. , Brandt Debora Y. C. , Nielsen Rasmus , Neaves Samuel , Timpson Nicolas , Crinklaw Austin , Lindestam Arlehamn Cecilia S. , Rautanen Anna , Kizito Dennison , Parks Tom , Auckland Kathryn , Elliott Kate E. , Mills Tara , Ewer Katie , Edwards Nick , Fatumo Segun , Webb Emily , Peacock Sarah , Jeffery Katie , van der Klis Fiona R. M. , Kaleebu Pontiano , Vijayanand Pandurangan , Peters Bjorn , Sette Alessandro , Cereb Nezih , Sirima Sodiomon , Madhi Shabir A. , Elliott Alison M. , McVean Gil , Hill Adrian V. S. , Sandhu Manjinder S.
Published: May 2024

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.
Screening and diagnosis of cardiovascular disease using artificial intelligence-enabled cardiac magnetic resonance imaging
Authors: Wang Yan-Ran , Yang Kai , Wen Yi , Wang Pengcheng , Hu Yuepeng , Lai Yongfan , Wang Yufeng , Zhao Kankan , Tang Siyi , Zhang Angela , Zhan Huayi , Lu Minjie , Chen Xiuyu , Yang Shujuan , Dong Zhixiang , Wang Yining , Liu Hui , Zhao Lei , Huang Lu , Li Yunling , Wu Lianming , Chen Zixian , Luo Yi , Liu Dongbo , Zhao Pengbo , Lin Keldon , Wu Joseph C. , Zhao Shihua
Published: May 2024

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.
Cognitive representations of intracranial self-stimulation of midbrain dopamine neurons depend on stimulation frequency
Authors: Millard Samuel J. , Hoang Ivy B. , Sherwood Savannah , Taira Masakazu , Reyes Vanessa , Greer Zara , O’Connor Shayna L. , Wassum Kate M. , James Morgan H. , Barker David J. , Sharpe Melissa J.
Published: May 2024

Dopamine neurons in the ventral tegmental area support intracranial self-stimulation (ICSS), yet the cognitive representations underlying this phenomenon remain unclear. Here, 20-Hz stimulation of dopamine neurons, which approximates a physiologically relevant prediction error, was not sufficient to support ICSS beyond a continuously reinforced schedule and did not endow cues with a general or specific value. However, 50-Hz stimulation of dopamine neurons was sufficient to drive robust ICSS and was represented as a specific reward to motivate behavior. The frequency dependence of this effect is due to the rate (not the number) of action potentials produced by dopamine neurons, which differently modulates dopamine release downstream.
Flip bifurcation analysis and mathematical modeling of cholera disease by taking control measures
Authors: Ahmad Aqeel , Abbas Fakher , Farman Muhammad , Hincal Evren , Ghaffar Abdul , Akgül Ali , Hassani Murad Khan
Published: May 2024

To study the dynamical system, it is necessary to formulate the mathematical model to understand the dynamics of various diseases which are spread in the world wide. The objective of the research study is to assess the early diagnosis and treatment of cholera virus by implementing remedial methods with and without the use of drugs. A mathematical model is built with the hypothesis of strengthening the immune system, and a ABC operator is employed to turn the model into a fractional-order model. A newly developed system SEIBR, which is examined both qualitatively and quantitatively to determine its stable position as well as the verification of flip bifurcation has been made for developed system. The local stability of this model has been explored concerning limited observations, a fundamental aspect of epidemic models. We have derived the reproductive number using next generation method, denoted as “$$R_{0}$$

R
0

”, to analyze its impact rate across various sub-compartments, which serves as a critical determinant of its community-wide transmission rate. The sensitivity analysis has been verified according to its each parameters to identify that how much rate of change of parameters are sensitive. Atangana–Toufik scheme is employed to find the solution for the developed system using different fractional values which is advanced tool for reliable bounded solution. Also the error analysis has been made for developed scheme. Simulations have been made to see the real behavior and effects of cholera disease with early detection and treatment by implementing remedial methods without the use of drugs in the community. Also identify the real situation the spread of cholera disease after implementing remedial methods with and without the use of drugs. Such type of investigation will be useful to investigate the spread of virus as well as helpful in developing control strategies from our justified outcomes.
Computation of molecular description of supramolecular Fuchsine model useful in medical data
Authors: Kosar Zunaira , Zaman Shahid , Ullah Asad , Siddiqui Muhammad Kamran , Belay Melaku Berhe
Published: May 2024

Supramolecular chemistry is a fascinating field that explores the interactions between molecules to create higher-order structures. In the case of the supramolecular chain of Fuchsine acid, which is a type of dye molecule, several chemical applications are possible. Fuchsine acid helps to make better medicine carriers that deliver drugs where they’re needed in the body, making treatments more effective and reducing side effects. It also helps create smart materials like sensors and self-fixing plastics, which are useful in electronics, keeping our environment clean, and making new materials. In sensing and detection, the supramolecular chain of Fuchsine acid utilizes as a sensor or detector for specific analyzes. In drug delivery, the supramolecular chains of Fuchsine acid incorporated into drug delivery systems. In recent years, a common method is linking a graph to a chemical structure and using topological descriptors to study it. This technique is becoming increasingly important over time. Topological descriptors gives very useful information while studying the topology of chemical graph. In this paper, we have computed the 3D structure of supramolecular graph of Fuchsine acid. We have computed an explicit expressions of ABC index, GA index, General Randi$$\acute{c}$$

c
´

index, first and second Zagreb index, hyper Zagreb index, H-index and F-index of supramolecular structure of Fushine acid.
EquiCity game: a mathematical serious game for participatory design of spatial configurations
Authors: Nourian Pirouz , Azadi Shervin , Bai Nan , de Andrade Bruno , Abu Zaid Nour , Rezvani Samaneh , Pereira Roders Ana
Published: May 2024

We propose a mathematical framework for developing social-choice games that are designed to mediate decision-making processes for city planning, urban area redevelopment, and architectural configuration of urban housing complexes. The proposed framework features a digital serious gaming approach for participatory design to support transparency and inclusion in the process of decision-making and ensure an equitable balance of sustainable development goals in spatial design outcomes. The mathematical process consists of a Markovian design machine for balancing the design decisions of actors, a massing configurator equipped with fuzzy logic and multi-criteria decision analysis, algebraic graph-theoretical accessibility evaluators, and automated solar-climatic evaluators using geospatial computational geometry. We demonstrate the effectiveness of the framework by implementing a multi-player online game that facilitates a participatory decision-making workshop for forming multi-functional building complexes by providing a generative configurator equipped with automated appraisal/scoring mechanisms for revealing the aggregate impact of alternatives. The EquiCity game empowers a group of decision-makers to reach a fair consensual spatial design by mathematically simulating many rounds of reasonable trade-offs between their decisions, with different levels of interest or control over various types of investments. The novelty of the framework is in its capability to encompass decision-making about the most idiosyncratic aspects of a site related to its heritage status and cultural significance to the most generic aspects such as balancing access to sunlight for the site while respecting ‘the right to sunlight’ of the neighbours of the site, ensuring coherence of the entire configuration with regards to a network of desired closeness ratings, the satisfaction of a programme of requirements, and intricately balancing individual development goals in conjunction with communal goals and environmental design codes.
Dual-branch information extraction and local attention anchor-free network for defect detection
Authors: Wang Xiaobin , Zhang Qiang , Chen Chengjun
Published: May 2024

In the production process, the presence of surface defects seriously affects the quality of industrial products. Existing defect detectors are not suitable for surface with scattered distribution and complex texture of defects. In this study, a dual-branch information extraction and local attention anchor-free network for defect detection (DLA-FCOS), which is based on the fully convolutional one-stage network, is proposed to accurately locate and detect surface defects of industrial products. Firstly, a dual-branch feature extraction network (DFENeT) is proposed and used to improve the extraction ability of complex defects. Then, a local feature enhancement module is proposed, and a residual connection is established to enrich local semantic information. Meanwhile, the self-attention mechanism is introduced to form local attentional residual feature pyramid networks (LA-RFPN) to eliminate the influences of feature misalignments. The mean average accuracy (mAP) and frames per second (FPS) of the proposed DLA-FCOS on the cut layer of the tobacco packet defect dataset (CLTP-DD) are 96.8% and 20.7, respectively, which meets the requirements for accurate and real-time defect detection. Meanwhile, the average accuracy of the proposed DLA-FCOS on the NEU-DET and GC10-DET datasets is 78.4% and 67.7%, respectively. The results demonstrate that the DLA-FCOS has good feasibility and high generalization capability to perform defect detection tasks of industrial products.
Antimicrobial efficacy of direct air gas soft jet plasma for the in vitro reduction of oral bacterial biofilms
Authors: Puca Valentina , Marinacci Beatrice , Pinti Morena , Di Cintio Federica , Sinjari Bruna , Di Marcantonio Maria Carmela , Mincione Gabriella , Acharya Tirtha Raj , Kaushik Nagendra Kumar , Choi Eun Ha , Sallese Michele , Guarnieri Simone , Grande Rossella , Perrotti Vittoria
Published: May 2024

The aim of this study was to evaluate the antimicrobial efficacy of an air gas soft jet CAP for its potential use in removing oral biofilms, given that plasma-based technologies have emerged as promising methods in periodontology. Two types of biofilms were developed, one byStreptococcus mutansUA 159 bacterial strain and the other by a complex mixture of saliva microorganisms isolated from a patient with periodontitis. This latter biofilm was characterized via Next Generation Sequencing to determine the main bacterial phyla. The CAP source was applied at a distance of 6 mm for different time points. A statistically significant reduction of both CFU count and XTT was already detected after 60 s of CAP treatment. CLSM analysis supported CAP effectiveness in killing the microorganisms inside the biofilm and in reducing the thickness of the biofilm matrix. Cytotoxicity tests demonstrated the possible use of CAP without important side effects towards human gingival fibroblasts cell line. The current study showed that CAP treatment was able to significantly reduce preformed biofilms developed by bothS. mutansand microorganisms isolated by a saliva sample. Further studies should be conducted on biofilms developed by additional saliva donors to support the potential of this innovative strategy to counteract oral pathogens responsible for periodontal diseases.
Epitaxial growth of high-quality GaN with a high growth rate at low temperatures by radical-enhanced metalorganic chemical vapor deposition
Authors: Dhasiyan Arun Kumar , Amalraj Frank Wilson , Jayaprasad Swathy , Shimizu Naohiro , Oda Osamu , Ishikawa Kenji , Hori Masaru
Published: May 2024

Using our recently developed radical-enhanced metalorganic chemical vapor deposition (REMOCVD) technique, we have grown gallium nitride (GaN) on bulk GaN and GaN on Si templates. Three features make up this system: (1) applying very high-frequency power (60 MHz) to increase the plasma density; (2) introducing H2 and N2 gas in the plasma discharge region to produce active NHx radical species in addition to nitrogen radicals; and (3) supplying radicals under remote plasma arrangement with a Faraday cage to suppress charged ions and photons. Using this new REMOCVD system, it was found that high-quality crystals can be grown at lower temperatures than that of MOCVD but the disadvantage was that the growth rate was smaller as 0.2–0.8 μm/h than that by MOCVD. In the present work, we have used a pBN inner shield to prevent the deactivation of radicals to increase the growth rate. The growth conditions such as the plasma power, trimethylgallium (TMG) source flow rate, N2 + H2 gas mixture flow rate, and the ratio of N2/H2 were optimized and it was found that the growth rate could be increased up to 3.4 μm/h with remarkably high crystalline quality comparable to that of MOCVD. The XRD-FWHM of GaN grown on the GaN/Si template and the bulk GaN substrate were 977 arcsec and 72 arcsec respectively. This work may be very promising to achieve high-power GaN/GaN devices.
Global seroprevalence of scrub typhus: a systematic review and meta-analysis
Authors: Dasgupta Sauvik , Asish Purushothaman Rajamani , Rachel Gladys , Bagepally Bhavani Shankara , Chethrapilly Purushothaman Girish Kumar
Published: May 2024

Scrub typhus, a neglected disease, is a significant health concern in the Tsutsugamushi triangle of the Asia–Pacific and has raised global concerns due to recent cases occurring outside this region. To estimate the global prevalence of scrub typhus, we conducted a systematic review and meta-analysis. We conducted a systematic search of PubMed, Scopus, and Embase databases for observational studies on scrub typhus. Using a random-effects model, we combined the prevalence estimates with inverse-variance weights while also evaluating heterogeneity and publication bias. Among 3551 reports screened, we identified 181 studies with 1,48,251 samples for inclusion in our synthesis. The overall pooled seroprevalence (95% confidence intervals) of scrub typhus infections was 24.93% (23.27–26.60). Gender-wise pooled prevalence was estimated to be 50.23% (47.05–53.40) for males and 48.84% (45.87–51.80) for females. Eschar prevalence was observed to be 30.34% (22.54–38.15) among the positive cases. One-fourth of all the samples tested positive for scrub typhus and eschar was present in one-third of these total positive cases, encompassing regions beyond the Tsutsugamushi triangle. This estimation underlines the importance of this neglected disease as a public health problem. Strengthening surveillance and implementing disease control measures are needed in the affected regions.
A fluorescently-tagged tick kinin neuropeptide triggers peristalsis and labels tick midgut muscles
Authors: Hernandez Jonathan R. , Xiong Caixing , Pietrantonio Patricia V.
Published: May 2024

Ticks are blood-feeding arthropods that require heme for their successful reproduction. During feeding they also acquire pathogens that are subsequently transmitted to humans, wildlife and/or livestock. Understanding the regulation of tick midgut is important for blood meal digestion, heme and nutrient absorption processes and for aspects of pathogen biology in the host. We previously demonstrated the activity of tick kinins on the cognate G protein-coupled receptor. Herein we uncovered the physiological role of the kinin receptor in the tick midgut. A fluorescently-labeled kinin peptide with the endogenous kinin 8 sequence (TMR-RK8), identical in the ticks Rhipicephalus microplus and R. sanguineus, activated and labeled the recombinant R. microplus receptor expressed in CHO-K1 cells. When applied to the live midgut the TMR-RK8 labeled the kinin receptor in muscles while the labeled peptide with the scrambled-sequence of kinin 8 (TMR-Scrambled) did not. The unlabeled kinin 8 peptide competed TMR-RK8, decreasing confocal microscopy signal intensity, indicating TMR-RK8 specificity to muscles. TMR-RK8 was active, inducing significant midgut peristalsis that was video-recorded and evaluated with video tracking software. The TMR-Scrambled peptide used as a negative control did not elicit peristalsis. The myotropic function of kinins in eliciting tick midgut peristalsis was established.
CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1
Authors: Khamaikawin Wannisa , Saisawang Chonticha , Tassaneetrithep Boonrat , Bhukhai Kanit , Phanthong Phetcharat , Borwornpinyo Suparerk , Phuphuakrat Angsana , Pasomsub Ekawat , Chaisavaneeyakorn Sujittra , Anurathapan Usanarat , Apiwattanakul Nopporn , Hongeng Suradej
Published: May 2024

Hematopoietic stem-cell (HSC) transplantation using a donor with a homozygous mutation in the HIV co-receptor CCR5 (CCR5Δ32/Δ32) holds great promise as a cure for HIV-1. Previously, there were three patients that had been reported to be completely cured from HIV infection by this approach. However, finding a naturally suitable Human Leukocyte Antigen (HLA)-matched homozygous CCR5Δ32 donor is very difficult. The prevalence of this allele is only 1% in the Caucasian population. Therefore, additional sources of CCR5Δ32/Δ32 HSCs are required. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) system is one method to mediate CCR5 knockout in HSCs that has been successfully employed as a gene editing tool in clinical trials. Additional anti-HIV-1 strategies are still required for broad-spectrum inhibition of HIV-1 replication. Here in this study, we combined an additional anti-HIV-1 therapy, which is C46, a cell membrane-anchored HIV-1 fusion inhibitor with the CRISPR/Cas9 mediated knockout CCR5. The combined HIV-1 therapeutic genes were investigated for the potential prevention of both CCR5 (R5)- and CXCR4 (X4)-tropic HIV-1 infections in the MT4CCR5 cell line. The combinatorial CRISPR/Cas9 therapies were superior compared to single method therapy for achieving the HIV-1 cure strategy and shows potential for future applications.
Deep-learning survival analysis for patients with calcific aortic valve disease undergoing valve replacement
Authors: Mohammadyari Parvin , Vieceli Dalla Sega Francesco , Fortini Francesca , Minghini Giada , Rizzo Paola , Cimaglia Paolo , Mikus Elisa , Tremoli Elena , Campo Gianluca , Calore Enrico , Schifano Sebastiano Fabio , Zambelli Cristian
Published: May 2024

Calcification of the aortic valve (CAVDS) is a major cause of aortic stenosis (AS) leading to loss of valve function which requires the substitution by surgical aortic valve replacement (SAVR) or transcatheter aortic valve intervention (TAVI). These procedures are associated with high post-intervention mortality, then the corresponding risk assessment is relevant from a clinical standpoint. This study compares the traditional Cox Proportional Hazard (CPH) against Machine Learning (ML) based methods, such as Deep Learning Survival (DeepSurv) and Random Survival Forest (RSF), to identify variables able to estimate the risk of death one year after the intervention, in patients undergoing either to SAVR or TAVI. We found that with all three approaches the combination of six variables, named albumin, age, BMI, glucose, hypertension, and clonal hemopoiesis of indeterminate potential (CHIP), allows for predicting mortality with a c-index of approximately$$80\%$$80%. Importantly, we found that the ML models have a better prediction capability, making them as effective for statistical analysis in medicine as most state-of-the-art approaches, with the additional advantage that they may expose non-linear relationships. This study aims to improve the early identification of patients at higher risk of death, who could then benefit from a more appropriate therapeutic intervention.
Facile fabrication of next-generation sustainable brick and mortar through geopolymerization of construction debris
Authors: Rahimpour Hamed , Amini Alireza Babaeian , Sharifi Fatemeh , Fahmi Ahmad , Zinatloo-Ajabshir Sahar
Published: May 2024

Waste from construction and demolition (also known as CDW) is one of the most harmful environmental issues. This study's primary goal is to produce new mortar and brick materials from recycled concrete powder (RCP) and recycled brick powder (RBP), two of the most popular CDW. Geopolymeric mortar and brick samples were produced by passing RCP and RBP through sieve No. 50 (with sand filler if necessary) and combining them with an alkaline solution made of water glass (WG) and NaOH. In this study, the mixture was then cured for three days at 80 °C in an oven. The effects of filler, RBP amount, WG amount, and the concentration of NaOH alkaline solution on the samples’ strength were examined. Additionally, XRF and SEM/XRD tests were performed to verify the materials' composition and microstructure. The mechanical strength of the samples showed an increase with the increase of RCP values, so the brick sample with filler showed the highest compressive strength, measuring 59.53 MPa. The study's samples exhibited strong mechanical properties. Additionally, all of the bricks' water absorption fell within the standard range. In summary, according to different standards, both waste concrete and waste brick can be used to produce geopolymer materials especially bricks for construction and paving purposes.
Amyloid-beta antibody binding to cerebral amyloid angiopathy fibrils and risk for amyloid-related imaging abnormalities
Authors: Söderberg Linda , Johannesson Malin , Gkanatsiou Eleni , Nygren Patrik , Fritz Nicolas , Zachrisson Olof , Rachalski Adeline , Svensson Anne-Sophie , Button Emily , Dentoni Giacomo , Osswald Gunilla , Lannfelt Lars , Möller Christer
Published: May 2024

Therapeutic antibodies have been developed to target amyloid-beta (Aβ), and some of these slow the progression of Alzheimer’s disease (AD). However, they can also cause adverse events known as amyloid-related imaging abnormalities with edema (ARIA-E). We investigated therapeutic Aβ antibody binding to cerebral amyloid angiopathy (CAA) fibrils isolated from human leptomeningeal tissue to study whether this related to the ARIA-E frequencies previously reported by clinical trials. The binding of Aβ antibodies to CAA Aβ fibrils was evaluated in vitro using immunoprecipitation, surface plasmon resonance, and direct binding assay. Marked differences in Aβ antibody binding to CAA fibrils were observed. Solanezumab and crenezumab showed negligible CAA fibril binding and these antibodies have no reported ARIA-E cases. Lecanemab showed a low binding to CAA fibrils, consistent with its relatively low ARIA-E frequency of 12.6%, while aducanumab, bapineuzumab, and gantenerumab all showed higher binding to CAA fibrils and substantially higher ARIA-E frequencies (25–35%). An ARIA-E frequency of 24% was reported for donanemab, and its binding to CAA fibrils correlated with the amount of pyroglutamate-modified Aβ present. The findings of this study support the proposal that Aβ antibody-CAA interactions may relate to the ARIA-E frequency observed in patients treated with Aβ-based immunotherapies.
Genomic properties of a Bartonella quintana strain from Japanese macaque (Macaca fuscata) revealed by genome comparison with human and rhesus macaque strains
Authors: Sato Shingo , Nishioka Emu , Kabeya Hidenori , Maruyama Soichi
Published: May 2024

Bartonella quintana, the causative agent of trench fever, is an intracellular bacterium that infects human erythrocytes and vascular endothelial cells. For many years, humans were considered the only natural hosts for B. quintana; however, it was recently discovered that wild Japanese macaques (Macaca fuscata) also serve as hosts for B. quintana. To elucidate the genetic characteristics of the B. quintana strain MF1-1 isolated from a Japanese macaque, we determined the complete genome sequence of the strain and compared it with those of strain Toulouse from a human and strain RM-11 from a rhesus macaque. General genomic features and orthologous gene cluster profiles are similar among the three strains, and strain MF1-1 is genetically closer to strain RM-11 than strain Toulouse based on the average nucleotide identity values; however, a significant inversion of approximately 0.68 Mb was detected in the chromosome of strain MF1-1. Moreover, the Japanese macaque strains lacked the bepA gene, which is responsible for anti-apoptotic function, and the trwL2, trwL4, and trwL6 genes, which may be involved in adhesion to erythrocytes of rhesus macaque and human. These features likely represent the genomic traits acquired by Japanese macaque strains in their host-associated evolution.
Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC
Authors: Hayhow Thomas G. , Williamson Beth , Lawson Mandy , Cureton Natalie , Braybrooke Erin L. , Campbell Andrew , Carbajo Rodrigo J. , Cheraghchi-Bashi Azadeh , Chiarparin Elisabetta , Diène Coura R. , Fallan Charlene , Fisher David I. , Goldberg Frederick W. , Hopcroft Lorna , Hopcroft Philip , Jackson Anne , Kettle Jason G. , Klinowska Teresa , Künzel Ulrike , Lamont Gillian , Lewis Hilary J. , Maglennon Gareth , Martin Scott , Gutierrez Pablo Morentin , Morrow Christopher J. , Nikolaou Myria , Nissink J. Willem M. , O’Shea Patrick , Polanski Radoslaw , Schade Markus , Scott James S. , Smith Aaron , Weber Judith , Wilson Joanne , Yang Bin , Crafter Claire
Published: May 2024

Targeting the estrogen receptor alpha (ERα) pathway is validated in the clinic as an effective means to treat ER+ breast cancers. Here we present the development of a VHL-targeting and orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of ERα. In vitro studies with this PROTAC demonstrate excellent ERα degradation and ER antagonism in ER+ breast cancer cell lines. However, upon dosing the compound in vivo we observe an in vitro-in vivo disconnect. ERα degradation is lower in vivo than expected based on the in vitro data. Investigation into potential causes for the reduced maximal degradation reveals that metabolic instability of the PROTAC linker generates metabolites that compete for binding to ERα with the full PROTAC, limiting degradation. This observation highlights the requirement for metabolically stable PROTACs to ensure maximal efficacy and thus optimisation of the linker should be a key consideration when designing PROTACs.