bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the role of Pax5 in development of taxane-resistant neuroendocrine like prostate cancers
Authors: Dutta Samikshan , Bhattacharya Sreyashi , Harris Hanna , Islam Ridwan , Bodas Sanika , Polavaram Navatha , Mishra Juhi , Das Dipanwita , Seshacharyulu Parthasarathy , Kalluchi Achyuth , Pal Anirban , Kohli Manish , Lele Subodh , Muders Michael , Batra Surinder , Ghosh Paramita , Datta Kaustubh , Rowley Michael
Published: December 2023

Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential. During t-NEPC transformation, adenocarcinomas lose their luminal features and adopt neuro-basal characteristics. Whether the adaptive neuronal characteristics of t-NEPC are responsible for such taxane resistance remains unknown. Pathway analysis from patient gene-expression databases indicates that t-NEPC upregulates various neuronal pathways associated with enhanced cellular networks. To identify transcription factor(s) (TF) that could be important for promoting the gene expression for neuronal characters in t-NEPC, we performed ATAC-Seq, acetylated-histone ChIP-seq, and RNA-seq in our NE-like cell line models and analyzed the promoters of transcriptionally active and significantly enriched neuroendocrine-like (NE-like) cancer-specific genes. Our results indicate that Pax5 could be an important transcription factor for neuronal gene expression and specific to t-NEPC. Pathway analysis revealed that Pax5 expression is involved in axonal guidance, neurotransmitter regulation, and neuronal adhesion, which are critical for strong cellular communications. Further results suggest that depletion of Pax5 disrupts cellular interaction in NE-like cells and reduces surface growth factor receptor activation, thereby, sensitizing them to taxane therapies. Moreover, t-NEPC specific hydroxymethylation of Pax5 promoter CpG islands favors Pbx1 binding to induce Pax5 expression. Based on our study, we concluded that continuous exposure to ARSI therapies leads to epigenetic modifications and Pax5 activation in t-NEPC, which promotes the expression of genes necessary to adopt taxane-resistant NE-like cancer. Thus, targeting the Pax5 axis can be beneficial for reverting their taxane sensitivity.
Deep learning genome-wide genetics through biregular sparse decoder layer: deriving new disease genetic associations and disease risk predictions
Authors: Gustafsson Mika , Dwivedi Sanjiv , Hellberg Sandra , Padyukov Leonid , Jornsten Rebecka
Published: December 2023

Genomic biobanks provide valuable resources for studying how genetic variation affects phenotypic differences and disease
susceptibility, driving advancements in human health. While unsupervised deep learning frameworks like autoencoders have
gained attention in other omics domains with fewer features, the computational complexity of genetic data has hindered their
application. To overcome this challenge, we propose a sparse biregular decoder layer for deep genetic autoencoders. This
layer significantly reduces the computational burden by using parameters at the scale of output nodes rather than multiplying
output and input nodes, as in a fully-connected layer. We trained the genetic autoencoders efficiently by storing and computing data in the internal memory, both independently for each chromosome and collectively for all autosomal chromosomes, creating a trans-chromosomal autoencoder. This approach enabled the discovery of modular associations at the gene level in the
interactome and facilitated the prediction of disease-associated single-nucleotide polymorphisms (SNPs) that yielded additional
highly significant variants to pairwise linkage disequilibrium score. Furthermore, we demonstrated the effectiveness of deep
autoencoders in enhancing the prediction performance for patients’ genetic risk scores by incorporating their embeddings into a LASSO model. This improvement was replicated in independent multiple sclerosis (MS) and rheumatoid arthritis (RA) cohort datasets, highlighting the potential of deep autoencoders in personalized medicine.
Community perceptions of incentives for minimally-invasive autopsy in Child Health and Mortality Prevention Surveillance (CHAMPS) in Western Kenya: A qualitative study
Authors: Ochola Kennedy Omondi , Ngere Sarah Hawi , Otieno Peter , Agaya Janet , Onyango Dickens , Akelo Victor , Omore Richard , Barr Beth A Tippett
Published: December 2023

Background
Incentives play an important role in improving research participation, and establishing ethically acceptable incentives is essential to preserving research integrity. The Child Health and Mortality Prevention Surveillance (CHAMPS) project uses minimally invasive tissue sampling (MITS) to ascertain the cause of death in children under five. Community beliefs about death and research with the dead necessitated a formative study on community perceptions about CHAMPS. Here we describe community perceptions about CHAMPS incentives, which include transportation of the body to place of burial, a US$40 contribution towards funeral expenses, and payment of the mortuary bill.
Methods
CHAMPS Kenya conducted a qualitative study of 88 community members between April 2017 and February 2018 using purposive sampling in an informal urban settlement in Kisumu County and in a rural Siaya county. Key informant interviews (n=29), semi-structured interviews (n=11), and focus group discussions (n=5) were conducted with community members, leaders, healthcare workers and caregivers. Respondents provided verbal consent, and interviews were audio-recorded and transcribed. Data management was completed on Nvivo 11, and analysis iterative, involving identification and collation of themes.
Results
Our study findings reveal positive perceptions towards study incentives because people believed that they were appropriate to the cultural context and well aligned to burial-related practices. Some expressed preference for non-monetary forms of incentives as monetary incentives is perceived as ‘selling’ of the body for research, and others felt that knowing and understanding the child’s cause of death should be enough motivation to participate. Respondents stated that the educational status of the participating family would influence their perception of study incentives; better-educated parents were believed to be less suspicious and view the incentives positively. However, some respondents believed that research incentives could raise suspicion among community members about the true intention of the research.
Conclusion
Our findings suggest that CHAMPS has achieved a positive balance of both cultural and financial value with the study incentives provided in the Kenya site. Increased community sensitization is needed to address negative perceptions that may be associated with research incentives.
Diversity of Plant Pollen Sources, Microbial communities and Phenolic compounds present in Bee pollen and Bee bread
Authors: Iorizzo Massimo , Albanese Gianluca , Letizia Francesco , Testa Bruno , Criscio Dalila Di , Petrarca Sonia , Martino Catello Di , Ganassi Sonia , Avino Pasquale , Pannella Gianfranco , Aturki Zeineb , Tedino Cosimo , De Cristofaro Antonio
Published: December 2023

The pollination of several crops, as well as wild plants, depends on honeybees. To get the nutrients required for growth and survival, honeybee colonies are dependent on pollen supply. Bee pollen (BP) is partially packed in honeycomb cells, and processed into beebread (BB) by microbial metabolism. The composition of pollen is highly variable and is mainly dependent on ecological habitat, geographical origin, honey plants, climatic conditions, and seasonal variations. Although there are important differences between the BP and the BB, little comparative chemical and microbiological data on this topic exists in the literature, particularly for samples with the same origin. In this study, BP and BB pollen samples were collected from two apiaries located in Campania and Molise regions of southern Italy. Phenolic profiles were detected via HPLC, while antioxidant activity was determined by ABTS assay. The Next Generation Sequencing (NGS) based on RNA analysis of 16S (rRNA), and Internal Transcribed Spacer (ITS2) regions was used to investigate the microbial community (bacteria and fungi) and botanical origin of the BP and BB. Chemical analysis showed a higher content of flavonols in BP (rutin, myricetin, quercetin, and kaempferol), while in BB there was a higher content of phenolic acids. The NGS analysis revealed that the microbial communities and pollen sources are dependent on the geographical location of apiaries. In addition, a diversity was highlighted between the microbial communities present in the BP and BB samples collected from each apiary.
Comparison of in vitro release profile of betaine from a multi-layered and single-layered electrospun structure based on Plantago ovata seed gum under the simulated digestive system
Authors: Abdollahzadeh Zahra , Honarvar Masoud , Ghavami Mehrdad
Published: December 2023

This study aimed to extract aspartic acid from sugar beet molasses using the cloud point method and encapsulate it in the structure of electrospun fast-dissolving poly(vinyl alcohol) (PVA)/Plantago ovata (P. ovata) seed gum fibers as the central layer of the sandwich structure. The outer layers of the sandwich structure were designed with corn zein electrospun fibers. The field emission scanning electron microscopy showed that the concentration of 35% w/v zein in 70% v/v ethanol provides uniform electrospun fibers for use as a delayed hydrophobic layer in a sandwich structure. The contact angle of the sandwich structure (92.45°) was significantly (p < 0.05) higher than the contact angle of electrospun mats of PVA/P. ovata seed gum containing 10% w/v sugar beet molasses betaine (53.5°). Fourier transform infrared spectroscopy and differential scanning calorimetry showed that the encapsulation process was successful. The use of a sandwich layer compared to the electrospun single-layer structure of PVA/P. ovata seed gum led to an increase in the thermal stability of betaine. In vitro release modeling showed that for all the structures of the Peppas-Sahlin model, it was the best model to describe the release behavior, and the Fickian diffusion mechanism was the dominant effective mechanism in betaine release.
NAT10 promotes chemoresistance of melanoma through regulating N4-acetylcytidine modification of DDX41 and ZNF746 mRNA
Authors: Liang Zuohui , Zeng Yuefen , Wang Li , Zhang Ying , Zhu Yun , Xu Shuangyan , Hao Yinglu , Zhao Haifeng
Published: December 2023

Background
Rapidly developed chemoresistance to dacarbazine (DTIC) is one of the major obstacles in management of melanoma in the clinic, however, roles and mechanism of epi-transcriptomic RNA modification in this process have not been investigated.
Method
We established DTIC-resistant (DR) melanoma cells for bulk RNA-sequencing, expressions of mRNAs was detected using qRT-PCR, and protein levels were determined using Western Blotting and Immunohistochemistry. Acetylated RNAs was detected by dot blotting and immunoprecipitation sequencing (acRIP-seq). A lung metastasis mouse model of melanoma was established to evaluate the anti-melanoma effects in vivo.
Results
We identified the expression of N-acetyltransferase 10 (NAT10), a catalytic enzyme for the N4-acetylcytidine (ac4C) modification of RNA, was significant upregulated in the DR cells. Clinically, NAT10 expression was elevated in disease progression samples and predicted a poor outcome. Using ac4C RNA immunoprecipitation (ac4c-RIP), we found mRNA of two C2H2 zinc finger transcriptional factors, DDX41and ZNF746, were targets of NAT10-mediated ac4C modification. Gain- and loss-of-functions either in NAT10, or in DDX41 and ZNF746, could alter chemosensitivity of melanoma accordingly, and the two target genes also negatively correlated with clinical outcomes. Finally, pharmacological inhibition of NAT10 with Remodelin sensitized melanoma cells to DTIC treatment in vitro and in a mouse xenograft model.
Conclusion
Our study elucidates previously unrecognized role of NAT10-mediated ac4c-modification in the chemoresistance of melanoma, and provides a rationale for developing new strategies to overcome chemoresistance of melanoma patients.
Determination of kilovoltage x-ray therapy depth doses with open-ended applicators
Authors: Perkins Anne , Healy Brendan , Coldrey Ben
Published: December 2023

The purpose of this work was to determine percentage depth dose (PDD) curves for kilovoltage x-rays from the WOmed-T105 unit, with open-ended steel applicators and beam qualities ranging from 0.5 to 4.2 mm Al. Measurements were made with parallel plate chambers in a water phantom, with extrapolation based on a fifth order polynomial used to estimate the surface dose. Measurements were also made with parallel plate chambers in a plastic water phantom, with thin plastic sheets used to obtain detailed measurements at shallow depths (less than 1 mm). Monte Carlo simulations were performed using the EGSnrc package, with two different sources as input: a SpekPy simulation of the x-ray beam and a full simulation of the x-ray tube, treatment head and applicators. Results showed that all four methods (two measurements and two simulations) agreed within the measurement uncertainty at depths greater than 2 mm. At shallow depths, significant differences were noted. At depths less than 0.1 mm, the full Monte Carlo simulation and the solid water measurements showed a sharp spike in surface dose which is attributed to electron contamination, which was not seen in the SpekPy Monte Carlo simulation or the extrapolated water measurements. At depths between 0.1 mm and 2 mm, beyond the range of contaminant electrons, the extrapolated water measurements underestimate the dose by up to 13% compared to the full Monte Carlo simulation and the solid water measurements., attributed to fluorescent photons generated in the applicators. This work demonstrates that for open-ended applicators, measurement of depth doses in water with extrapolation of surface dose has the potential to significantly underestimate the dose at shallow depths between the surface and 2 mm, even after eliminating electron contamination from the beam.
Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers
Authors: Rhee Joon Haeng , Tan Wenzhi , Thiruppathi Jayalakshmi , Hong Seol Hee , Puth Sao , Pheng Sophea , Mun Bo-Ram , Choi Won-Seok , Lee Kyung-Hwa , Park Hyun-Sun , Nguyen Duc , Lee Min-Cheol , JEONG Kwangjoon , Zheng Jin Hai , Kim Young , Lee Shee Eun
Published: December 2023

Alzheimer’s disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Immunotherapy targeting and resolving the pathological tau aggregates is known to improve cognitive deficits in AD animal models. The repeat domain of tau (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Considering that TauRD forms the structural core of tau aggregates, the development of immunotherapy selectively targeting TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated a recombinant TauRD polypeptide forming neurofibrillary tangle (NFT)-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum could also specifically recognize pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested the vaccine efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, such as memory deficits, and ameliorated tauopathy progression. More notably, the survival of the vaccinated mice was dramatically extended. Conclusively, we have developed a mucosal vaccine exclusively targeting pathological tau conformers and preventing disease progression.
Psychoactive Substance Use and Associated Factors Among Mohammed First University Students, Oujda, Morocco: A Cross-Sectional Study
Authors: Essadi Adil , Aissaoui Hanane , Yeznasni Asmae , Lekfif Asmae , Sebbar Sanae , Atassi Mariam , Abda Naima
Published: December 2023

Background: The use of psychoactive substances, including tobacco, alcohol, and others, remains a major public health problem. However, few studies have been conducted on Moroccan university students. This study aimed to assess the prevalence and associated factors of substance use among students at Mohammed First University, Oujda, Morocco.
Methods: We conducted this cross-sectional study with students enrolled at one of the Mohammed First University of Oujda's institutes as part of the 2021–202 academic year. We used a self-administered survey to collect data anonymously. We cleaned the data and then entered it into IBM SPSS Statistics 21 for analysis. Data analysis involved descriptive statistics as well as univariate and multivariate analysis. We considered a P value < 0.05 as the level of significance.
Results: In this study, out of 500 students we asked to complete the survey, 478 responded; the response rate was 95.6%. The average age was 21.1± 3.0, and the M/F sex ratio was 0.97. The prevalence of psychoactive substance use among Oujda University students was 28.7%. The most commonly used substances were tobacco (24.1%), alcohol (15.9%), cannabis (13.4%), sedatives (6.9%), stimulants (5.2%), and cocaine (4.4%).
Male sex, age > 20 years, self-financing, school failure (one year repeated or more), the practice of a leisure activity, the presence of a personal medical or psychiatric history, and the presence of a family medical history were all significantly associated with the use of psychoactive substances.
Conclusion: Our study revealed a significant prevalence of psychoactive substance use among university students in Oujda, highlighting the need for interventions at various levels. Further analytical studies are necessary to better understand the initiation and maintenance of psychoactive substance use and to identify all associated factors to enhance prevention strategies against substance use disorders.
Machine Learning Analysis of Gene Expression Profiles ofPyroptosis-Related Differentially Expressed Genes in IschemicStroke Revealed Potential Targets for Drug Repurposing
Authors: Hei Changchun , Li Xiaowen , Wang Ruochen , Liu Ping , Dong Xialan , Li P. Andy , Zheng Weifan , Niu Jianguo , Yang Xiao
Published: December 2023

The relationship between ischemic stroke (IS) and pyroptosis centers on the inflammatory response elicited by cerebral tissue damage during an ischemic stroke event. However, an in-depth mechanistic understanding of their connection remains limited. This study aims to comprehensively analyze the gene expression patterns of pyroptosis-related differentially expressed genes (PRDEGs) by employing integrated IS datasets and machine learning techniques. The primary objective was to develop classification models to identify crucial PRDEGs integral to the IS process. Leveraging three distinct machine learning algorithms (LASSO, Random Forest, and Support Vector Machine), models were developed to differentiate between the Control and the IS patient samples. Through this approach, a core set of 10 PRDEGs consistently emerged as significant across all three machine learning models. Subsequent analysis of these genes yielded significant insights into their functional relevance and potential therapeutic approaches. In conclusion, this investigation underscores the pivotal role of pyroptosis pathways in IS and identifies pertinent targets for therapeutic development and drug repurposing.
Meta Generative Image and Text Data Augmentation Optimization
Authors: Zhang Enzhi , Dong Bochen , Wahib Mohamed , Zhong Rui , Munetomo Masaharu
Published: December 2023

This paper proposes a method called Meta Generative Data Augmentation Optimization (MGDAO) to overcome limited types of operations for the policy-based automatic data augmentation method. While traditional data augmentation methods have relied on expert intuition to determine effective transformations, recent approaches have attempted to generate data augmentation strategies automatically. However, these automatic methods can still suffer from limited operation sets and difficulty training conditional generative models. To address these issues, MGDAO replaces the limited operations space in the AutoAugment series with a deep-style generator and replaces the discriminator in a generative adversarial model with the validation loss of the target model. These replacements released fixed image operations and made MGDAO useful for sequential data. The generator learns to transform the data from the training domain to the validation data domain. It is further used to generate augmented samples to train the target model and reduce the validation loss. Experiments on classification benchmarks of few-shot image and text-based datasets show that MGDAO achieves competitive results compared to data auto-augmentation methods.
Low handgrip strength is associated with worse functional outcomes in long-Covid
Authors: AMARAL Camila Miriam Suemi Sato Barros do Amaral , GOULART Cássia da Luz Goulart , SILVA Bernardo Maia da Silva , VALENTE Jefferson Valente , REZENDE Anna Gabriela Rezende , FERNANDES Eduardo Fernandes , CUBAS-VEGA Nadia Cubas-Vega , BORBA Mayla Gabriela Silva Borba , SAMPAIO Vanderson Sampaio , MONTEIRO Wuelton Monteiro , MELO Gisely Cardoso de Melo , LACERDA Marcus Lacerda , ARÊAS Guilherme Peixoto Tinoco Arêas , Almeida-Val Fernando Almeida-Val
Published: December 2023

The diagnosis of long-Covid is troublesome, even when functional limitations are present. Dynapenia is a decrease in muscle strength and power production and may explain in part these limitations. This study aimed to identify the distribution and possible association of dynapenia with functional assessment in patients with long-Covid. A total of 113 inpatients with COVID-19 were evaluated by functional assessment 120 days post-acute severe disease. Body composition, respiratory muscle strength, spirometry, six-minute walk test (6MWT) and hand-grip strength (HGS) were assessed. Dynapenia was defined as HGS < 30kg/f (men), and < 20kg/f (women). Twenty-five (22%) participants were dynapenic, presenting lower muscle mass (p < 0.001), worse forced expiratory volume in the first second (FEV1) (p = 0.0001), lower forced vital capacity (p < 0.001), and inspiratory (p = 0.007) and expiratory (p = 0.002) peek pressures, as well as worse 6MWT performance (p < 0.001). Dynapenia was associated with worse FEV1, MEP, and 6MWT, independent of age (p < 0.001). Patients with dynapenia had higher ICU admission rates (p = 0.01) and need for invasive mechanical ventilation (p = 0.007) during hospitalization. The HGS is a simple, reliable, and low-cost measurement that can be performed in outpatient clinics in low- and middle-income countries. Thus, HGS may be used as a proxy indicator of functional impairment in this population.
Bendamustine, prednisone and bortezomib (BPV) induction therapy prior autologous stem cell transplantation (ASCT) in 135 newly diagnosed multiple myeloma patients: comparison between patients with normal and impaired renal function
Authors: Fricke Susann , Wang Song-Yau , Holzhey Tanja , Zehrfeld Thomas , Hammerschmidt Doreen , Neumann Dominik , Becker Cornelia , Hoffmann Franz-Albert , Schwarzer Andreas , Reifenrath Kolja , Fenchel Klaus , Edelmann Thomas , Braunert Leanthe , Holzvogt Madlen , Andrea Marc , Vucinic Vladan , Franke Georg-Nikolaus , Heyn Simone , Weibl Saskia , Jentzsch Madlen , Scholz Markus , Platzbecker Uwe , Merz Maximilian , Pönisch Wolfram
Published: December 2023

Introduction:
Autologous stem cell transplantation (ASCT) is the standard first line treatment for younger patients with multiple myeloma (MM). Bortezomib and bendamustine have both been identified as rapidly acting and well-tolerated drugs for patients with MM-induced renal failure. In this retrospective study we analyzed the efficacy of induction therapy with a combination bendamustine, prednisone and bortezomib (BPV) prior to ASCT in newly diagnosed MM-patients (NDMM) depending on severity of renal impairment.
Methods
135 patients with NDMM were treated with BPV-induction.
Results
The majority of patients (n = 117; 87%) responded after BPV-induction with 9 sCR, 3 CR, 12 nCR, 39 VGPR, and 54 PR. After first ASCT ORR increased to 99% with 33 sCR, 10 CR, 32 nCR, 41 VGPR and 17 PR. Median PFS was 47 months and OS at 60 months was 67%. Patients were divided into four groups depending on severity of renal impairment: A (n = 13) with eGFR < 15mL/min, B (n = 15) 15–29mL/min, C (n = 19) 30-59mL/min and D (n = 88) ≥ 60mL/min. We observed no significant difference in PFS between patients with normal/mild, moderate, severe renal dysfunction and renal failure/dialysis (50 vs 47 vs 34 vs 24 months, p = 0.05) and in 60 months OS (69 vs 72 vs 58 vs 70%, p = 0.23). The renal response rate improved from 61% after BPV to 74% following ASCT.
Conclusions
These results indicate that BPV-induction followed by ASCT is feasible, effective and well tolerated in patients with MM-induced renal failure. Furthermore, we showed that pretreatment with short-term bendamustine had no negative impact on stem cell mobilization.
Correlation between Hospital Management Factors with Cancer Death Rates: An Example from G7 Countries
Authors: Caglar Yezdan , Ozdal Macide Artac
Published: December 2023

Objectives Cancer, which is characterized by the abnormal, uncontrolled growth and spread of cells in the body, is one of the most imminent diseases of our era. Cancer can occur anywhere, regardless of geographic boundaries, and it is a problem and health issue both for developed and developing countries that any person from any country in any age group may be affected. The main aim is to identify the relation between the cancer death rates and hospital management over two decades.Methods Within the scope of this study, the correlation between the cancer death rates in G7 countries (Germany, United States, United Kingdom, Italy, France, Japan and Canada) and nurse, doctor, hospital stay, hospital discharge and hospital bed rates were statistically analysed for the period between 2000 and 2020.Results High levels of health in developed countries and associated managerial improvement of hospitals reduce the cancer death rates. The study findings were interpreted through Eviews statistics software, which is developed by the company called Quantitative Micro Software (QMS). Eviews is a very common program for econometric analysis allowing performance of time series, panel data and horizontal sectional data analysis. For this study, this analytical tool was used due to its time series generation feature for data breakdown. For the analysis of sufficient number of studies and estimation of any unknown regression parameter, the test panel was tested with pedroni cointegration in addition to the ordinary least squares test.Conclusions The test results concluded a long term (20-year) correlation between the variables.
Impact of hepatic inflammation and fibrosis on the recurrence and long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after hepatectomy
Authors: Hao Xiangyong , Xu Liangliang , Lan Xiang , Li Bo , Cai Hui
Published: December 2023

Background: Underlying liver disease is correlated with hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV) infection. However, the impact of hepatic inflammation and fibrosis on the patients’ prognoses remains unclear.
Methods: The clinicopathological data of 638 HBV-infected patients with early-stage HCC between 2017 and 2019 were prospectively collected. Hepatic inflammation and fibrosis were evaluated by experienced pathologists using the Scheuer score system. Survival analysis was analyzed using the Kaplan–Meier analysis.
Results: Application of the Scheuer scoring system revealed that 50 (7.9%), 274 (42.9%), and 314 (49.2%) patients had minor, intermediate, and severe hepatic inflammation, respectively, and 125 (15.6%), 150 (23.5%), and 363 (56.9%) patients had minor fibrosis, advanced fibrosis, and cirrhosis, respectively. Patients with severe hepatitis tended to have a higher rate of HBeAg positivity, higher HBV-DNA load, elevated alanine aminotransferase (ALT) levels, and a lower proportion of capsule invasion (all p <0.05). There were no significant differences in the recurrence-free and overall survival among the three groups (p =0.52 and p=0.66, respectively). Patients with advanced fibrosis or cirrhosis had a higher proportion of HBeAg positivity and thrombocytopenia, higher FIB-4, and larger tumor size compared to those with minor fibrosis (all p <0.05). Patients with minor, advanced fibrosis, and cirrhosis had similar prognoses after hepatectomy (p=0.48 and p=0.70). The multivariate analysis results indicated that neither hepatic inflammation nor fibrosis was an independent predictor associated with prognosis.
Conclusions: For HBV-related HCC patients receiving antiviral therapy, hepatic inflammation and fibrosis had little impact on the post-hepatectomy prognosis.
“If it all goes digital we’ll have to learn”: Facilitators and barriers to uptake of digital health in British South Asians with cardiometabolic disease
Authors: Ramasawmy Mel , Sunkersing David , Persson Dan Roland , Poole Lydia , Patel Kiran , Modha Shivali , Sajid Madiha , Gill Paramjit , Stevenson Fiona , Khan Nushrat , Banerjee Amitava
Published: December 2023

Background: Although availability and utilisation of digital health interventions (DHIs) for management of diabetes and cardiovascular disease (“cardiometabolic disease”) have increased, they may exacerbate health inequalities. South Asians have increased cardiometabolic risk, but their experiences of DHIs are poorly investigated and characterised.
Objective: To explore facilitators and barriers to DHI uptake and use in South Asian individuals in the UK with cardiometabolic disease.
Methods: Mixed-methods approach encompassing online/face-to-face/individual interviews (n=45) and survey (n=100). After informed consent, transcription and coding, we conducted a thematic analysis informed by a framework for inequalities in DHIs to examine perceptions at the individual, healthcare professional, societal and intervention level.
Results: Participants described an intersection of factors resulting in varied digital skills and confidence within the community, including individual characteristics, awareness, and support. COVID-19 restrictions acted as both a positive (use of online shopping and social media increasing digital confidence) and negative (lack of access to health services) drivers to DHI uptake. Participants made recommendations for improving DHI uptake in the health service and policy area, such as promotion and upskilling through culturally and language-appropriate avenues such as community organisations and outlets. Participants suggested DHI design improvements should focus on literacy, numeracy, accessibility, and cultural appropriateness.
Conclusions: DHIs have the potential to support South Asian populations in the UK to prevent and manage cardiometabolic disease. In order to improve their uptake, approaches to their implementation should consider community diversity to provide appropriate promotion, education, and support.
Research on safety path planning for ship navigation based on EGA2CO algorithm
Authors: wang peiliang , Zhang Ting , wang Zhiming
Published: December 2023

For solving the problem that only the path length is considered in the traditional ship navigation path planning,the EGA2CO algorithm is proposed with the rasterize map as simulation background.Firstly, to solve the problems of "oblique wall penetration" and inconsistent time steps, a hexagonal raster is used to draw the simulation map; then, the scale and parameters of the GA algorithm are determined by setting the evolution rate based on the elite genetic algorithm (EGA); secondly, the heuristic function and pheromone update strategy adapting the raster map are designed to construct the Ant Colony Optimization (ACO) algorithm; finally, the EGA2CO algorithm is constructed using the optimal fusion point strategy, and the evaluation functions comprised of path economy and safety are designed.The simulation results show that when EGA2CO is used for path planning, its search speed and convergence speed are significantly improved, and the obtained paths can effectively avoid obstacles, which can effectively improve the safety of the navigation path on the basis of ensuring the economy of the ship's navigation path.
Analytical study of EPB shield spewing discrimination in auxiliary air pressure mode
Authors: Zheng Jingfan , Yu Jun , Li Dongkai , He Zhen , Zhang Zhizhong , Yang Feng
Published: December 2023

Considering the effect of auxiliary air pressure on the shield seepage field, the spewing problem is analyzed by using an analytical method. Soil conditioning is currently the main method that can be used to prevent and control the occurrence of shield spewing, but there is a lack of research on how low the soil permeability coefficient should be conditioned. To further study the mechanism of the occurrence of spewing, this paper uses the variable separation method and the superposition principle to derive an analytical solution of the two-dimensional seepage field of the shield under the auxiliary air pressure mode, and calculates the critical permeability coefficient of spewing based on a previous study. The accuracy of the analytical solution is verified by comparison with numerical simulations. Parametric analyses show that when the auxiliary air pressure fluctuates at the lower design limit, it slightly helps to avoid spewing, but as the auxiliary air pressure becomes greater than the water pressure at the bottom of the cutter face, the risk of spewing will be greater than that of the closed mode. After the water pressure at the bottom of the cutter face is greater than 28m, the critical permeability coefficient of a typical size shield will be less than 10-4cm/s, and the empirical way of controlling the permeability coefficient to 10-4~10-3cm/s has a risk of spewing. By comparison with the spewing example, the prediction of the critical permeability coefficient of spewing by the analytical solution is proven to be effective.
Unveiling the Therapeutic Potential of Dl-3-n-butylphthalide in Migraine: Activating the Nrf2 Pathway to Alleviate Oxidative Stress and Neuronflammation
Authors: Liu Yingyuan , Gong Zihua , Zhai Deqi , Yang Chunxiao , Lu Guangshuang , Wang Shuqing , Xiao Shaobo , Li Chenhao , Chen Ludan , Lin Xiaoxue , Zhang Shuhua , Yu Shengyuan , Dong Zhao
Published: December 2023

Background: Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in its pathogenesis and chronicity. Existing evidence indicates the capacity of Dl-3-n-butylphthalide (NBP) to mitigate oxidative stress and inflammation, thereby conferring neuroprotective benefits in many central nervous system diseases. However, the specific therapeutic implications of NBP in the context of migraine remain to be elucidated. Methods: We established a C57BL/6 mouse model of chronic migraine (CM) using recurrent intraperitoneal injections of nitroglycerin (NTG, 10mg/kg), and prophylactic treatment was simulated by administering NBP (30mg/kg, 60mg/kg, 120mg/kg) by gavage prior to each NTG injection. Mechanical threshold was assessed using von Frey fibres, and photophobia and anxious behaviours were assessed using a light/dark box and elevated plus maze. Expression of c-Fos, calcitonin gene-related peptide (CGRP), Nucleus factor erythroid 2-related factor 2 (Nrf2) and related pathway proteins in the trigeminal nucleus candis (TNC) were detected by Western blotting (WB) or immunofluorescence (IF). The expression of IL-1β, IL-6, TNF-α, Superoxide dismutase (SOD) and malondialdehyde (MDA) in TNC and CGRP in plasma were detected by ELISA. A reactive oxygen species (ROS) probe was used to detect the expression of ROS in the TNC. Results: At the end of the modelling period, chronic migraine mice showed significantly reduced mechanical nociceptive thresholds, as well as photophobic and anxious behaviours. Pretreatment with NBP attenuated nociceptive sensitization, photophobia, and anxiety in the model mice, reduced expression levels of c-Fos and CGRP in the TNC and activated Nrf2 and its downstream proteins HO-1 and NQO-1. By measuring the associated cytokines, we also found that NBP reduced levels of oxidative stress and inflammation. Most importantly, the therapeutic effect of NBP was significantly reduced after the administration of ML385 to inhibit Nrf2. Conclusions: Our data suggest that NBP may alleviate migraine by activating the Nrf2 pathway to reduce oxidative stress and inflammation in migraine mouse models, confirming that it may be a potential drug for the treatment of migraine. Graphical Abstract
Investigation of modern leakage based on numerical and geochemical modeling near a municipal well field in Memphis, Tennessee.
Authors: Hasan Khairul , Waldron Brian , Larsen Daniel , Schoefernacker Scott
Published: December 2023

Local leakage processes and potential migration pathways of modern water (< 60 years) from the shallow aquifer, into the underlying semiconfined Memphis aquifer, were evaluated to assess the vulnerability of groundwater in Memphis Light, Gas and Water’s (MLGW) Sheahan well field. To identify the source(s) and pathways of modern water, integrated hydrostratigraphic analysis, numerical modeling, hydrologic tracers, and geochemical modeling were utilized. The percentage of modern water present in Memphis aquifer production wells is estimated using inverse geochemical modeling, lumped parameter modeling, and solute transport modeling with Modular Transport, 3-Dimensional, Multi-Species model (MT3DMS). The mixing percentages determined from lumped parameter modeling and MT3DMS are generally in agreement except well 87A, estimating up to 14.3% and 15.3%, respectively. The significant mixing fraction difference at 87A might account for the missing hydrogeologic connection in the groundwater model on the eastern part of the well field. Estimates for the apparent age of the modern water derived from MT3DMS fall within the age range obtained from environmental tracer data (3H/3He). However, the age distributions from the MT3DMS model are limited to 60 years or less, resulting in a younger mean age than the tracer-based apparent ages. Thus, the MT3DMS model, calibrated with long-term tracer data could simulate the mean age and mixing percentage of modern water while emphasizing the importance of accurate hydrogeologic conceptualizations at the Sheahan well field. As a result, tracer data and solute transport modeling can identify vulnerabilities and ensure the long-term sustainability of the Sheahan well field.
Approximate nearest neighbor search by Cyclic Hierarchical Product Quantization
Authors: Xu Zhi , Zhou Mengdong , Liu Yuxuan , Zhao Longyang , Liu Jiajia
Published: December 2023

Vector quantization (VQ) is a widely used Approximate Nearest Neighbor (ANN) search method. By constructing multiple codebooks, VQ can create more codeword vectors with lower memory consumption, enabling the indexing of large-scale database. In recent years, many VQ-based methods have been proposed, but the codeword vectors constructed in these methods are often underutilized due to lack of data support, and the unimodal data distribution within the cell is not considered. To address these issues, this paper introduces a new quantization method called Cyclic Hierarchical Product Quantization (CHPQ). This method firstly constructs a hierarchical quantization structure in each subspace, with each hierarchical structure composed of several sub-quantizers. Then, the codebook is locally optimized under the sub-quantizers according to the data distribution of each cell, significantly improving quantization performance compared to other methods and greatly enhancing the accuracy of ANN search. Additionally, this paper proposes a new hierarchical quantization structure named cyclic hierarchical structure, which can generate more diverse codeword vectors in different cells compared to the traditional hierarchical quantization structure. Extensive experiments on two publicly available datasets demonstrate that CHPQ outperforms existing methods in terms of retrieval accuracy while maintaining comparable computational efficiency.
Infrared Thermography Techniques for Boundary Layer State Visualisation
Authors: Davis William , Atkins Nicholas R.
Published: December 2023

The rapid decarbonisation of the power generation and aviation sectors will require a move away from incremental development, exposing designers and researchers to the risk of unexpected results from uncertainty in boundary layer state. This problem already exists for parts developed with fully turbulent assumptions, but in novel design spaces the risk increases for both real components, where previous knowledge of similar designs may be inapplicable, and particularly in experimental testing of scaled models, where reducing Reynolds number can result in a drastic change in flow topology that skews the conclusions of a test. Computational methods struggle to reliably predict boundary layer state so experimental techniques for diagnosing boundary layer state are needed.
Infrared thermography (IR) is a non-invasive technique that offers simple, fast visualisation of boundary layer state with no additional instrumentation. IR is relatively uncommon in the literature and there is minimal information available on the best practices for its use. This paper aims to encourage the adoption of IR as a diagnostic tool by demonstrating routes for optimisation and pointing out pitfalls to avoid. A low-order model is developed and used to predict how the signal-to-noise ratio (SNR) of an IR visualisation changes depending on the thermal design of the test piece. It is shown that in low-speed flows, with active heating from the surface, the SNR is maximised through a suitable choice of surface insulation while in high-speed flows, where passive temperature differences are used, there is a crossover between heat transfer and recovery temperature effects that results in an SNR of zero, an effect that can arise in both steady-state and transient experiments. Experimental validation of the 1D model in both flow regimes is shown alongside two case studies on the use of IR in sub-scale testing where uncertainty in boundary layer state results in critical differences from the full-scale flow.
Myofibroblast-specific inhibition of ASPP1 alleviates myocardial fibrosis by enhancing p53 degradation
Authors: Pan Zhenwei , Li Shangxuan , Zhang Yang , Zhao Yinfeng , Zhai Yinghe , Sun Chongsong , Guo Yang , Zhang Xiaofang , Zhang Lingmin , Tian Tao , Yang Ying , Pei Yao , Li Jialiang , Xuan Lina , Lu Yanjie , Yang Baofeng
Published: December 2023

In the healing process of myocardial infarction, cardiac fibroblasts are activated and serious cardiac fibrosis developed, which eventually leads to cardiac remodeling and heart failure. Our recent study showed that ASPP1 (apoptosis stimulating of p53 protein 1) promotes cardiomyocyte apoptosis by enhancing nuclear trafficking of p53. As p53 is a key regulator of cardiac fibroblast activation, we thus explored the influence of ASPP1 on myocardial fibrosis and the molecular mechanisms related to p53.Here, we observed ASPP1 was increased after 4 weeks of myocardial infarction (MI). Both global and myofibroblast-specific knockout of ASPP1 in mice mitigated cardiac dysfunction, fibrosis and remodeling after MI. Strikingly, ASPP1 produced opposite influence on p53 level and cell fate of cardiac fibroblast than cardiomyocytes. Knockdown of ASPP1 increased p53 level and inhibited the activity of cardiac fibroblasts. The immunofluorescent staining revealed that upon TGF-b1 stimulation ASPP1 accumulates in the cytoplasm of fibroblasts while the level of p53 was reduced, and inhibition of ASPP1 increased p53 level and promoted p53 nuclear translocation. Mechanistically, ASPP1 directly binds to deubiquitinase OTUB1 and prevents its binding with p53, thereby promoting the ubiquitination and degradation of p53. Targeting ASPP1 may be a promising strategy for the treatment of myocardial fibrosis.
Molding without melting: Investigation of thermoplastic polymers with regard to their suitability as mold material
Authors: Neumann Fabian , Rings Benedikt , Golombek Hannes
Published: December 2023

Context:
The choice of material, manufacturing process, and molding tool significantly effects the quality, environmental impact, and cost efficiency of fiber reinforced polymer (FRP) components. Producing one-piece hollow profiles with smooth inner surfaces and undercuts presents major challenges for conventional mold concepts. A promising solution are shape memory polymers as tooling material.
Objectives
This study aims to identify thermoplastic polymers which are suitable as mold material in the FRP manufacturing process. The overarching objective is to develop a high-rate manufacturing process for one-piece FRP hollow profiles with undercuts.
Methods
First a manufacturing and curing process for an FRP is introduced. From this, boundary conditions for the mold material are defined. An assessment of the properties of thermoplastic polymers from literature research is carried out. An evaluation matrix allows the preselection of four polymers. PET, PPS, PA6 and PA66 are further analyzed by DSC and DMA.
Results
Semi-crystalline thermoplastics are more suitable as mold material than amorphous ones. When heated above their glass transition temperature (Tg) the elastomeric state allows for one-piece demolding. The material properties of 31 semi-crystalline polymers are assessed. PET, PPS, PA6 and PA66 are found as most likely suitable as mold materials for the introduced curing process. Their Tg is evaluated by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA).
Conclusion
PET, PA6 and PA66 meet the process parameters of the defined FRP production process. Further research has to be carried out regarding their shape memory behavior and demolding capabilities.