bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio Design for Footwear Innovation: Growing Sneaker Components with Composite Mycelium-based Materials
Authors: Rapagnani Nicholas , van Bezooijen Aart , Borruso Luigimaria , Mimmo Tanja , Bouaicha Oussama
Published: May 2024

Footwear design has traditionally followed a linear and profit-driven approach, leading to present ecological and social issues. Contemporarily, bio design experimentations have shown several opportunities in growing materials. We explore the use of mycelium composite cultures in the production of sneakers components, aiming to combat climate change, foster multidisciplinary collaborations, and promote sustainable material values. In this study, we implemented microbiological procedures to cultivate Plerotus Ostreatus mycelium as footwear components within scaled-down 3D printed moulds holding hemp fibres, natural tanned goat leather, and 3D printed TPU as substrate materials. To assess material flexibility, we experimented with various glycerol solutions. Mycelium demonstrated its ability to grow on diverse substrates, particularly hemp fibres, colonizing both its surface and bottom. However, challenges arose with leather and TPU, as the hyphae struggled to digest and entangle heavy, large pieces of animal or synthetic-based substrates, rendering the materials fragile and unstable. Additionally, glycerol did not effectively enhance the flexibility of the composite materials. Our findings suggest that fungi hold promise for growing circular footwear components directly in required shapes, utilizing digitally manufactured moulds. To enhance mycelium structure stability and mechanical properties, further exploration of different fungi species alongside smaller scale ground substrate materials is recommended.
Perceived Parenting Styles and College Student’s Psychosocial Adjustment
Authors: Asare Lionel K.
Published: May 2024

Extant literature has established the impact that parenting has on the development of children within specific domains of behavioral outcomes such as deviance, prone to depression among others. However, there are still unanswered questions regarding the role of parenting styles in the development of psychosocial skills of emerging adults. This study assessed retrospective information from college students (n=138) about their parents’ parenting styles during their early years of life and how it has impacted the development of their perceived self-esteem, self-efficacy, and academic self-efficacy. Results showed that the best optimal environment for parenting that is likely to yield positive psychosocial variables are parental responsiveness and involvement. This study further showed that, even though parents may show a higher level of involvement and responsiveness to their children, the co-occurring of these variables with higher level of parental demandingness tends to neutralize the positive effects of parental responsiveness and involvement.
Aplikasi Pemantauan dan Peringatan Dini untuk Energi Baru Terbarukan Berbasis Android dengan Restful Api (Studi Kasus Kajian EBT Polinema dan PT. PLN
Authors: Yuniari Nilam , Ed Dien Habibie , Ariyanto Rudy
Published: May 2024

Renewable energy sources are environmentally friendly energy sources, because they do not cause environmental changes and do not cause climate change and global warming. Due to the influence of astronomy and geography, Indonesia is a country that is rich in potential new and renewable energy sources such as geothermal energy, solar, water, wind, marine and bioenergy. In the context of providing sustainable electricity, PT. PLN is collaborating with the Malang State Polytechnic to increase the use of renewable energy to become a power plant that utilizes kinetic energy and solar energy. In the development process, monitoring of power plants is currently still done manually. Monitoring the condition of power plants will be more effective and efficient if it is done automatically. Technological trends that support these applications are now starting to increase, especially on smartphones with the Android operating system. From a standalone application, it has now turned into an application that can be connected to other applications using a global network known as Restful API and is integrated with Internet of Things (IoT) technology which can monitor the condition of generators in real time and provide emergency information. Therefore, there is a need for applications that can assist in the process of developing power plants that can monitor and provide early warning notifications. The system designed and implemented uses a MySQL database and the Java programming language in the Android Studio application. From the test results using a Likert Scale, a feasibility percentage of 86.5% of users stated that the application was in accordance with its function and was able to make it easier for users, namely admins, operators, stakeholders, asset managers, project owners and PLN in monitoring EBT generators.
Komunikasi Kooperatif D2D dengan Bantuan UAV Berbasis AF/DF Multi Relay dengan Dampak Hardware Impairment
Authors: Annysa Aprilya  , Meyra Chusna Mayarakaca  , Arifin  , Faridatun Nadziroh  , Yoedy Moegiharto
Published: May 2024

This work investigates the implementation of hybrid AF and DF relay protocols in D2D multi-relay wireless communication systems. To obtain system performance we propose four scenarios for using the AF and DF relay protocols and three S – R and R – D distance conditions that have an impact on system performance in terms of throughput values. From the simulation results it is concluded that the R – D distance will produce the highest SNR value which produces the best system throughput value compared to . The simulation results also prove that applying the AF relay protocol to all relays produces better SNR values ​​and better throughput values ​​than applying the DF relay protocol. Simulation results with the impact of hardware impairment (HI) levels show that system performance in the first scenario is actually worse than other scenarios when the κ value is above 0.1.
O Papel da Grande Firma na Dinâmica Industrial: notas para uma síntese pós-keynesiana-evolucionária
Authors: Kippe Rubinsztajn Igor
Published: May 2024

Este artigo tem como objetivo estudar a contribuição das decisões de investimento das grandes firmas capitalistas para a dinâmica de emergência e evolução das indústrias, por meio da fertilização cruzada entre três abordagens distintas, para articular estes fenômenos e conceitos: a noção de incerteza e sua relação com as decisões de investir em Keynes e na literatura pós-keynesiana, na análise pós-keynesiana, mais precisamente de Steindl, sobre o crescimento das firmas e sua relação com a dinâmica industrial e na abordagem evolucionária da mudança técnica. Com base na literatura revisada, o trabalho revela que essas estratégias – por vezes sobrepostas – dependerão essencialmente do grau de preferência pela liquidez; do hiato entre a taxa de acumulação interna das grandes firmas e a taxa de crescimento da demanda da indústria (ou seja, a maturidade da indústria); e das dimensões econômicas da tecnologia (ou seja, as oportunidades, cumulatividade e apropriabilidade tecnológicas).
Desoneração da folha salarial: uma caracterização setorial a partir dos dados da RAIS e das Contas Nacionais
Authors: De Britto Rocha Gustavo , De Queiroz Stein Alexandre , Oliveira Santos Diogo , Arthur  , Prates Romero João
Published: May 2024

As discussões sobre a política de desoneração da folha salarial retornaram aos noticiários em decorrência do veto, em outubro de 2023, pelo presidente Lula ao projeto de lei que previa a prorrogação da medida até 2027. Porém, a retomada do debate público não veio acompanhada do rigor técnico adequado para analisar a complexidade da lei e seus efeitos. Este artigo tem o objetivo de contribuir para este debate com uma caracterização detalhada dos setores efetivamente beneficiados pela política, utilizando agregações setoriais consistentes com a CNAE. A análise revela que não é apropriado falar em 17 setores desonerados, mas em 141 atividades (classes CNAE) desoneradas. Além disso, os dados com agregação setorial correta mostram que as atividades efetivamente desoneradas tiveram pior resultado em termos de empregos e massa salarial (queda) do que as atividades não desoneradas (estabilidade) entre 2010 e 2021. Adicionalmente, entre as 15 atividades que mais empregam no país, estão apenas 3 atividades desoneradas. Portanto, a medida não está alinhada com as boas práticas de políticas industriais e tecnológicas, faltando critérios claros sobre os setores a serem beneficiados, além de metas de desempenho e temporalidade para cada setor.
EDUCAÇÃO COMO ESTRATÉGIA DE DESENVOLVIMENTO SUSTENTÁVEL
Authors: PALAZZO SAMANTHA RIBAS , OLIVEIRA GILSON BATISTA
Published: May 2024

Este artigo analisa a importância da educação como estratégia de desenvolvimento sustentável (ODS) com base na literatura econômica e nas Metas de ODS da ONU. Economistas reconhecem a educação como uma estratégia eficaz para o desenvolvimento nacional, oferecendo vantagens econômicas e sociais. A ODS 4 destaca a necessidade de uma educação inclusiva, equitativa e de qualidade ao longo da vida para todos. A educação é vista como um meio de acesso a empregos melhores, redução de desigualdades e estímulo ao desenvolvimento tecnológico. Estudos de caso, como a implantação da Universidade Federal da Integração Latino-Americana (UNILA) em Foz do Iguaçu, demonstram seu impacto não apenas econômico, mas também social e cultural. Portanto, é fundamental que economistas, governantes e autoridades priorizem investimentos em educação como parte integrante de seus planos de desenvolvimento sustentável.
Hidden dual mathematical symmetry in the genetic code
Authors: Nieto-Marín N. , Nieto-Marín C. C. , Nieto-Marín I. , Nieto J. A.
Published: May 2024

We describe the genetic code in terms of numbers that help us to find several dual symmetries. Our formulation can even be rewritten regarding the up-down and right-left dual concepts. We argue that our work may bring many topological tools to studying the DNA molecule, including the Grassmann-Plücker coordinates, which are important in mathematical and physical contexts.
Explainable AI models for predicting liquefaction-induced lateral spreading
Authors: Hsiao Cheng-Hsi , Kumar Krishna , Rathje Ellen M.
Published: May 2024

Introduction: Earthquake-induced liquefaction can cause substantial lateral spreading, posing threats to infrastructure. Machine learning (ML) can improve lateral spreading prediction models by capturing complex soil characteristics and site conditions. However, the “black box” nature of ML models can hinder their adoption in critical decision-making.

Method: This study addresses this limitation by using SHapley Additive exPlanations (SHAP) to interpret an eXtreme Gradient Boosting (XGB) model for lateral spreading prediction, trained on data from the 2011 Christchurch Earthquake.

Result: SHAP analysis reveals the factors driving the model's predictions, enhancing transparency and allowing for comparison with established engineering knowledge. Notably, the SHAP values expose an unexpected behavior in the PGA feature. Moreover, the results demonstrate that the XGB model successfully identifies the importance of soil characteristics derived from Cone Penetration Test (CPT) data in predicting lateral spreading, validating its alignment with domain understanding.

Discussion: This work highlights the value of explainable machine learning for reliable and informed decision-making in geotechnical engineering and hazard assessment.
Systematic conceptual design strategies for the recovery of metals from E-waste
Authors: Palav Samarth D. , Torres Ana I. , Biegler Lorenz T.
Published: May 2024

As the consumption of electronics increases worldwide, significant strain is posed on both the availability of mineral resources and the accumulation of waste due to their disposal. Recovering valuable minerals from e-waste can potentially alleviate both. This paper discusses the systematic design of processes for the recycling of waste printed circuit boards (WPCB). After reviewing the relevant processing steps, the generation of processing superstructures is explained. Next, a formulation of the optimization problem is presented to identify the best processing pathway, and the use of process simulators to specify optimization-relevant parameters. These ideas are described in detail via a WPCB to metals case study.
Research progress in isolation and identification of rumen probiotics
Authors: Wu Runmin , Ji Peng , Hua Yongli , Li Hongya , Zhang Wenfei , Wei Yanming
Published: May 2024

With the increasing research on the exploitation of rumen microbial resources, rumen probiotics have attracted much attention for their positive contributions in promoting nutrient digestion, inhibiting pathogenic bacteria, and improving production performance. In the past two decades, macrogenomics has provided a rich source of new-generation probiotic candidates, but most of these “dark substances” have not been successfully cultured due to the restrictive growth conditions. However, fueled by high-throughput culture and sorting technologies, it is expected that the potential probiotics in the rumen can be exploited on a large scale, and their potential applications in medicine and agriculture can be explored. In this paper, we review and summarize the classical techniques for isolation and identification of rumen probiotics, introduce the development of droplet-based high-throughput cell culture and single-cell sequencing for microbial culture and identification, and finally introduce promising cultureomics techniques. The aim is to provide technical references for the development of related technologies and microbiological research to promote the further development of the field of rumen microbiology research.
Does intervention engagement mediate physical activity change in a web-based computer-tailored physical activity intervention?—Secondary outcomes from a randomised controlled trial
Authors: Vandelanotte Corneel , Short Camille E. , Plotnikoff Ronald C. , Schoeppe Stephanie , Alley Stephanie J. , To Quyen , Rebar Amanda L. , Duncan Mitch J.
Published: May 2024

Introduction

The relationship between intervention engagement and behaviour change may vary depending on the specific engagement metric being examined. To counter this composite engagement measures may provide a deeper understanding of the relationship between engagement and behaviour change, though few studies have applied such multidimensional engagement metrics. The aim of this secondary analysis of RCT data was to examine how a composite engagement score mediates the effect of a web-based computer-tailored physical activity intervention.

Methods

501 inactive Australian adults were randomised to a no-treatment control or intervention group. Intervention participants received 8 sessions of web-based personalised physical activity advice over a 12-week intervention period and the ability to complete action plans. Change in physical activity was assessed using Actigraph accelerometers at baseline, 3-months and 9-months. Engagement with the intervention (i.e., a composite score including frequency, intensity, duration and type) was continuously assessed during the intervention period using website tracking software and database metrics. Generalised structural equation models were used to examine how a composite engagement score mediated intervention effects at 3 months and 9 months.

Results

At 3 months, mediation analysis revealed that the intervention group had significantly higher engagement scores than the control group [a-path exp(b) = 6.462, 95% CI = 5.121–7.804, p < 0.001]. Further, increased engagement with the intervention platform was associated with an increased time spent in moderate-to-vigorous physical activity [ab-coefficient exp(b) = 1.008, 95% CI = 1.004–1.014, P < 0.001]; however, the magnitude of this effect was small. There were no significant mediation effects at the 9-month time point.

Discussion

The findings suggest that a composite intervention engagement score has a small positive influence on physical activity changes and that other factors (e.g., behaviour change techniques) are likely to be more important drivers of behaviour change.
Vascular service provision during the COVID-19 pandemic worsened major amputation rates in socially deprived diabetic populations
Authors: AlMajali Ali S. , Richards Thomas , Yusuf Syed Waquar , Telgenkamp Bjorn
Published: May 2024

Introduction

The Coronavirus Disease – 2019 (COVID-19) pandemic significantly impacted healthcare service provision and put diabetic patients at increased risk of adverse health outcomes. We aimed to assess the impact of the COVID-19 pandemic on the incidence and demographic shift of major lower-limb amputation in diabetic patients.

Methods

We performed a retrospective analysis of diabetic patient records undergoing major lower-limb amputation between 01/03/2019 and 01/03/2021 at the Royal Sussex County Hospital, the regional arterial hub for Sussex. Primary outcomes were amputation incidence rates and patient demographics compared between the prepandemic and pandemic cohorts.

Results

The incidence rate ratio of major lower-limb amputations shows a drop in amputations during the pandemic compared to pre-pandemic (IRR 0.82; 95% CI 0.57–1.18). Data suggests a shift in the social deprivation background of patients receiving amputations to disproportionately affect those in the more deprived 50% of the population (p=0.038). Younger patients received more amputations during the pandemic compared to prepandemic levels (p=0.001).

Conclusion

Results suggest that during the COVID-19 pandemic there was a paradoxical reduction in amputations compared to prepandemic levels. However, changes to the demographic makeup of patient’s receiving amputations are alarming as younger, and more deprived patients have been disproportionately affected by the pandemic.
shRNA-mediated gene silencing of HDAC11 empowers CAR-T cells against prostate cancer
Authors: Zhang Hongmei , Yao Jie , Ajmal Iqra , Farooq Muhammad Asad , Jiang Wenzheng
Published: May 2024

Epigenetic mechanisms are involved in several cellular functions, and their role in the immune system is of prime importance. Histone deacetylases (HDACs) are an important set of enzymes that regulate and catalyze the deacetylation process. HDACs have been proven beneficial targets for improving the efficacy of immunotherapies. HDAC11 is an enzyme involved in the negative regulation of T cell functions. Here, we investigated the potential of HDAC11 downregulation using RNA interference in CAR-T cells to improve immunotherapeutic outcomes against prostate cancer. We designed and tested four distinct short hairpin RNA (shRNA) sequences targeting HDAC11 to identify the most effective one for subsequent analyses. HDAC11-deficient CAR-T cells (shD-NKG2D-CAR-T) displayed better cytotoxicity than wild-type CAR-T cells against prostate cancer cell lines. This effect was attributed to enhanced activation, degranulation, and cytokine release ability of shD-NKG2D-CAR-T when co-cultured with prostate cancer cell lines. Our findings reveal that HDAC11 interference significantly enhances CAR-T cell proliferation, diminishes exhaustion markers PD-1 and TIM3, and promotes the formation of T central memory TCM populations. Further exploration into the underlying molecular mechanisms reveals increased expression of transcription factor Eomes, providing insight into the regulation of CAR-T cell differentiation. Finally, the shD-NKG2D-CAR-T cells provided efficient tumor control leading to improved survival of tumor-bearing mice in vivo as compared to their wild-type counterparts. The current study highlights the potential of HDAC11 downregulation in improving CAR-T cell therapy. The study will pave the way for further investigations focused on understanding and exploiting epigenetic mechanisms for immunotherapeutic outcomes.
New findings on retinal microvascular changes in patients with primary COVID-19 infection: a longitudinal study
Authors: Zhang Chenxi , Cheng Shiyu , Chen Huan , Yang Jingyuan , Chen Youxin
Published: May 2024

Purpose

To investigate the longitudinal alterations of retinal microvasculature in patients with primary coronavirus disease 2019 (COVID-19) infection.

Methods

A cohort of participants, who had never been infected with COVID-19, was recruited between December 2022 and May 2023 at Peking Union Medical College Hospital in Beijing, China. Participants underwent comprehensive ophthalmologic examinations and fundus imaging, which included color fundus photography, autofluorescence photography, swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). If participants were infected with COVID-19 during the study, follow-ups with consistent imaging modality were conducted within one week and two months after recovery from the infection.

Results

31 patients (61 eyes), with a mean age of 31.0 ± 7.2 years old, were eligible for this study. All participants contracted mild COVID-19 infection within one month of baseline data collection. The average period was 10.9 ± 2.0 days post-infection for the first follow-up and 61.0 ± 3.5 days for the second follow-up. No clinical retinal microvasculopathy features were observed during the follow-ups. However, SS-OCTA analysis showed a significant increase in macular vessel density (MVD) from 60.76 ± 2.88% at baseline to 61.59 ± 3.72%(p=0.015) at the first follow-up, which subsequently returned to the baseline level of 60.23 ± 3.33% (p=0.162) at the two-month follow-up. The foveal avascular zone (FAZ) remained stable during the follow-ups with areas of 0.339 ± 0.097mm2, 0.342 ± 0.093mm2, and 0.344 ± 0.098mm2 at the baseline, first follow-up (p=0.09) and second follow-up (p=0.052), respectively. Central macular thickness, cube volume and ganglion cell-inner plexiform layer showed a transient decrease at the first follow-up(p<0.001, p=0.039, p=0.002, respectively), and increased to baseline level at the two-month follow-up(p=0.401, p=0.368, p=0.438, respectively).

Conclusion

Mild COVID-19 infection may temporarily and reversibly impact retinal microvasculature, characterized by a transient increase in retinal blood flow during the early recovery phase, which returns to the pre-infection level two months post-infection.
Factors contributing to sepsis-associated encephalopathy: a comprehensive systematic review and meta-analysis
Authors: Zhang Zhiyang , Guo Li , Jia Lijing , Duo Hong , Shen Limin , Zhao Heling
Published: May 2024

Background

This study aims to systematically assess the risk factors, the overall strength of association, and evidence quality related to sepsis-associated encephalopathy.

Methods

A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, and Embase for cohort or case-control studies published up to August 2023 on risk factors associated with sepsis-related encephalopathy. The selected studies were screened, data were extracted, and the quality was evaluated using the Newcastle–Ottawa Scale. Meta-analysis was performed using RevMan 5.3 software. The certainty of the evidence was assessed using the GRADE criteria.

Results

A total of 13 studies involving 1,906 participants were included in the analysis. Among these studies, 12 were of high quality, and one was of moderate quality. Our meta-analysis identified six risk factors significantly associated with Serious Adverse Events (SAE). These included APACHE II, SOFA, age, tau protein, and IL-6, which were found to be risk factors with significant effects (standard mean difference SMD: 1.24–2.30), and albumin, which was a risk factor with moderate effects (SMD: −0.55). However, the certainty of evidence for the risk factors identified in this meta-analysis ranged from low to medium.

Conclusion

This systematic review and meta-analysis identified several risk factors with moderate to significant effects. APACHE II, SOFA, age, tau protein, IL-6, and albumin were associated with sepsis-related encephalopathy and were supported by medium- to high-quality evidence. These findings provide healthcare professionals with an evidence-based foundation for managing and treating hospitalized adult patients with sepsis-related encephalopathy.
Biochar-bacteria-plant combined potential for remediation of oil-contaminated soil
Authors: Fang Xin , Zhang Mei , Zheng Pufan , Wang Haomin , Wang Kefan , Lv Juan , Shi Fuchen
Published: May 2024

Oil pollution is a common type of soil organic pollution that is harmful to the ecosystem. Bioremediation, particularly microbe-assisted phytoremediation of oil-contaminated soil, has become a research hotspot in recent years. In order to explore more appropriate bioremediation strategies for soil oil contamination and the mechanism of remediation, we compared the remediation effects of three plants when applied in combination with a microbial agent and biochar. The combined remediation approach of Tagetes erecta, microbial agent, and biochar exhibited the best plant growth and the highest total petroleum hydrocarbons degradation efficiency (76.60%). In addition, all of the remediation methods provided varying degrees of restoration of carbon and nitrogen contents of soils. High-throughput sequencing found that microbial community diversity and richness were enhanced in most restored soils. Some soil microorganisms associated with oil degradation and plant growth promotion such as Cavicella, C1_B045, Sphingomonas, MND1, Bacillus and Ramlibacter were identified in this study, among which Bacillus was the major component in the microbial agent. Bacillus was positively correlated with all soil remediation indicators tested and was substantially enriched in the rhizosphere of T. erecta. Functional gene prediction of the soil bacterial community based on the KEGG database revealed that pathways of carbohydrate metabolism and amino acid metabolism were up-regulated during remediation of oil-contaminated soils. This study provides a potential method for efficient remediation of oil-contaminated soils and thoroughly examines the biochar–bacteria–plant combined remediation mechanisms of oil-contaminated soil, as well as the combined effects from the perspective of soil bacterial communities.
Lentinula edodes substrate formulation using multilayer perceptron-genetic algorithm: a critical production checkpoint
Authors: Safaie Naser , Salehi Mina , Farhadi Siamak , Aligholizadeh Ali , Mahdizadeh Valiollah
Published: May 2024

Shiitake (Lentinula edodes) is one of the most widely grown and consumed mushroom species worldwide. They are a potential source of food and medicine because they are rich in nutrients and contain various minerals, vitamins, essential macro- and micronutrients, and bioactive compounds. The reuse of agricultural and industrial residues is crucial from an ecological and economic perspective. In this study, the running length (RL) of L. edodes cultured on 64 substrate compositions obtained from different ratios of bagasse (B), wheat bran (WB), and beech sawdust (BS) was recorded at intervals of 5 days after cultivation until the 40th day. Multilayer perceptron-genetic algorithm (MLP-GA), multiple linear regression, stepwise regression, principal component regression, ordinary least squares regression, and partial least squares regression were used to predict and optimize the RL and running rate (RR) of L. edodes. The statistical values showed higher prediction accuracies of the MLP-GA models (92% and 97%, respectively) compared with those of the regression models (52% and 71%, respectively) for RL and RR. The high degree of fit between the forecasted and actual values of the RL and RR of L. edodes confirmed the superior performance of the developed MLP-GA models. An optimization analysis on the established MLP-GA models showed that a substrate containing 15.1% B, 45.1% WB, and 10.16% BS and a running time of 28 days and 10 h could result in the maximum L. edodes RL (10.69 cm). Moreover, the highest RR of L. edodes (0.44 cm d−1) could be obtained by a substrate containing 30.7% B, 90.4% WB, and 0.0% BS. MLP-GA was observed to be an effective method for predicting and consequently selecting the best substrate composition for the maximal RL and RR of L. edodes.
Increased hippocampal epigenetic age in the Ts65Dn mouse model of Down Syndrome
Authors: Ravaioli Francesco , Stagni Fiorenza , Guidi Sandra , Pirazzini Chiara , Garagnani Paolo , Silvani Alessandro , Zoccoli Giovanna , Bartesaghi Renata , Bacalini Maria Giulia
Published: May 2024

Down syndrome (DS) is a segmental progeroid genetic disorder associated with multi-systemic precocious aging phenotypes, which are particularly evident in the immune and nervous systems. Accordingly, people with DS show an increased biological age as measured by epigenetic clocks. The Ts65Dn trisomic mouse, which harbors extra-numerary copies of chromosome 21 (Hsa21)-syntenic regions, was shown to recapitulate several progeroid features of DS, but no biomarkers of age have been applied to it so far. In this pilot study, we used a mouse-specific epigenetic clock to measure the epigenetic age of hippocampi from Ts65Dn and euploid mice at 20 weeks. Ts65Dn mice showed an increased epigenetic age in comparison with controls, and the observed changes in DNA methylation partially recapitulated those observed in hippocampi from people with DS. Collectively, our results support the use of the Ts65Dn model to decipher the molecular mechanisms underlying the progeroid DS phenotypes.
A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study
Authors: Rushendran Rapuru , Singh Anuragh , Ankul Singh S. , Chitra Vellapandian , Ilango Kaliappan
Published: May 2024

Background

Migraines affect one billion individuals globally, with a higher occurrence among young adults and women. A significant survey in the United States indicated that 17.1% of women and 5.6% of men suffer from migraines. This study seeks to investigate the potential connection between NLRP3 and MMP9 in migraine pathology.

Methods

The research involved searching databases such as PubMed, Scopus, Science Direct, Google Scholar, and Proquest, with the search concluding on March 31, 2024. Following PRISMA guidelines, PICO data were collected, focusing exclusively on animal models induced by Nitroglycerine (10 mg/kg), while excluding clinical studies.

Results

The study, originally registered in Prospero Reg. No. CRD42022355893, conducted bias analysis using SYRCLE’s RoB tool and evaluated author consensus using GraphPad v9.5.1. Out of 7,359 search results, 22 papers met the inclusion criteria. Inter-rater reliability among reviewers was assessed using Cohen’s kappa statistics.

Conclusion

This review summarizes 22 preclinical studies on Nitroglycerin (NTG), NLRP3, MMP9, and related biomarkers in migraine. They reveal that NTG, especially at 10 mg/kg, consistently induces migraine-like symptoms in rodents by activating NLRP3 inflammasome and stimulating proinflammatory molecule production.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, CRD42022355893.
Developmental trajectory of care dependency in older stroke patients
Authors: Lin Qinger , Dong Xiaohang , Huang Tianrong , Zhou Hongzhen
Published: May 2024

Background

Stroke is the leading cause of death in China. Older stroke survivors often have other chronic conditions, not only musculoskeletal deterioration due to age, but also changes in body image that can be brought on by stroke and other diseases, making them unable to take good care of themselves and dependent on others. The degree of dependency affects the rehabilitation progress of stroke survivors and shows dynamic changes that need to be recognized.

Objectives

This study investigates the trajectory of dependency changes in older stroke patients with comorbidities and analyze the influencing factors.

Methods

Grounded in the Chronic Illness Trajectory Framework (CITF), a longitudinal study was conducted from February 2023 to October 2023, tracking 312 older stroke patients with comorbidities admitted to two tertiary hospitals in Guangzhou. Care dependency levels were assessed using Care Dependency Scale on admission day 5 (T0), at discharge (T1), 1 month post-discharge (T2), and 3 months post-discharge (T3). Growth Mixture Model were utilized to identify trajectory categories, and both univariate analysis and multivariate logistic regression methods were employed to explore factors associated with different developmental trajectories.

Results

A total of four developmental trajectories were fitted, C1 (high independence-slow increased group, 52.0%), C2 (moderate independence-rapid increased group, 13.0%), C3 (moderate independence-slow increased group, 25.0%), and C4 (low independence-increased and decreased group, 10.0%). Length of hospital stay, place of residence, level of social support, residual functional impairments, NIHSS score, and BI index independently influence the trajectory categories.

Conclusion

There is heterogeneity in care dependency among older stroke patients with comorbidities. Most patients gradually reduce their dependency and become more independent, but others remain dependent for an extended period of time. It is recommended to focus on patients who live in rural areas, have low social support, have high admission NIHSS scores and have residual functional impairment, and provide them with personalized continuity of care and rehabilitation services in order to reduce care dependency and the burden of care, and to improve patients’ quality of life.
A multimodal approach to automated hierarchical assessment of bulbar involvement in amyotrophic lateral sclerosis
Authors: Rong Panying , Heidrick Lindsey , Pattee Gary L.
Published: May 2024

Introduction

As a hallmark feature of amyotrophic lateral sclerosis (ALS), bulbar involvement leads to progressive declines of speech and swallowing functions, significantly impacting social, emotional, and physical health, and quality of life. Standard clinical tools for bulbar assessment focus primarily on clinical symptoms and functional outcomes. However, ALS is known to have a long, clinically silent prodromal stage characterized by complex subclinical changes at various levels of the bulbar motor system. These changes accumulate over time and eventually culminate in clinical symptoms and functional declines. Detection of these subclinical changes is critical, both for mechanistic understanding of bulbar neuromuscular pathology and for optimal clinical management of bulbar dysfunction in ALS. To this end, we developed a novel multimodal measurement tool based on two clinically readily available, noninvasive instruments—facial surface electromyography (sEMG) and acoustic techniques—to hierarchically assess seven constructs of bulbar/speech motor control at the neuromuscular and acoustic levels. These constructs, including prosody, pause, functional connectivity, amplitude, rhythm, complexity, and regularity, are both mechanically and clinically relevant to bulbar involvement.

Methods

Using a custom-developed, fully automated data analytic algorithm, a variety of features were extracted from the sEMG and acoustic recordings of a speech task performed by 13 individuals with ALS and 10 neurologically healthy controls. These features were then factorized into 10 composite outcome measures using confirmatory factor analysis. Statistical and machine learning techniques were applied to these composite outcome measures to evaluate their reliability (internal consistency), validity (concurrent and construct), and efficacy for early detection and progress monitoring of bulbar involvement in ALS.

Results

The composite outcome measures were demonstrated to (1) be internally consistent and structurally valid in measuring the targeted constructs; (2) hold concurrent validity with the existing clinical and functional criteria for bulbar assessment; and (3) outperform the outcome measures obtained from each constituent modality in differentiating individuals with ALS from healthy controls. Moreover, the composite outcome measures combined demonstrated high efficacy for detecting subclinical changes in the targeted constructs, both during the prodromal stage and during the transition from prodromal to symptomatic stages.

Discussion

The findings provided compelling initial evidence for the utility of the multimodal measurement tool for improving early detection and progress monitoring of bulbar involvement in ALS, which have important implications in facilitating timely access to and delivery of optimal clinical care of bulbar dysfunction.
Cubeb (Piper cubeba L.): nutritional value, phytochemical profiling and dermacosmeceutical properties
Authors: Drissi Badr Eddine , Mahdi Ismail , Ortaakarsu Ahmet Buğra , Abdelfattah Mohamed A. O. , Bakrim Widad Ben , Khatib Sohaib , Mahmoud Mona F. , Bouissane Latifa , Sobeh Mansour
Published: May 2024

Introduction

Cubeb, Piper cubeba L., has been used for centuries in traditional medicine and culinary practices, with a wide range of biological and pharmacological activities.

Objective

Herein, we determined the phytochemical profile, mineral, fatty acids, and amino acid contents of P. cubeba berries and assessed the dermacosmeceutical properties of their water extract and essential oil (EO). These included assessing their antioxidant and antibacterial activities as well as their in vitro inhibitory activities against tyrosinase and elastase enzymes. In addition, molecular docking and molecular dynamics studies were performed on the major identified compounds of the EO.

Results and discussion

A total of forty-three compounds belonging to organic acids, phenolic acids and flavonoids were found in the water extract, while 36 volatile compounds were identified in the EO with Z-isoeugenol, dihydroeugenol, β-pinene, E-caryophyllene, and 1,8-cineole as major constituents. The berries were found to be rich in sodium and iron, have moderate zinc content along with low contents of total nitrogen, phosphorus, and potassium. Amino acid analysis revealed a considerable concentration of isoleucine and phenylalanine, whereas 11,14,17-eicosatrienoic acid and linoleic acid were identified as the major fatty acids. In the DPPH and FRAP assays, the water extract elicited considerable antioxidant activity compared to the reference compounds. Enzyme inhibitory assays revealed that the EO had a potential to inhibit tyrosinase and elastase enzymes with IC50 values of 340.56 and 86.04 μg/mL, respectively. The water extract and EO completely inhibited the bacterial growth at MIC of 50 mg/mL and 20%, respectively. At sub-MIC concentrations, the extract and the EO substantially reduced the biofilm formation by up to 26.63 and 77.77%, respectively, as well as the swimming and swarming motilities in a dose-dependent manner. Molecular docking and molecular dynamics showed that the five main components of P. cubeba EO could be the major contributors to the elastase and tyrosinase inhibitory effect.

Conclusion

This study emphasizes the promising potential of P. cubeba as a valuable source of natural compounds that can be utilized for the development of innovative pharmaceuticals, dietary supplements, and dermacosmeceutical agents.
A glutamatergic biomarker panel enables differentiating Grade 4 gliomas/astrocytomas from brain metastases
Authors: Lange Falko , Gade Richard , Einsle Anne , Porath Katrin , Reichart Gesine , Maletzki Claudia , Schneider Björn , Henker Christian , Dubinski Daniel , Linnebacher Michael , Köhling Rüdiger , Freiman Thomas M. , Kirschstein Timo
Published: May 2024

Background

The differentiation of high-grade glioma and brain tumors of an extracranial origin is eminent for the decision on subsequent treatment regimens. While in high-grade glioma, a surgical resection of the tumor mass is a fundamental part of current standard regimens, in brain metastasis, the burden of the primary tumor must be considered. However, without a cancer history, the differentiation remains challenging in the imaging. Hence, biopsies are common that may help to identify the tumor origin. An additional tool to support the differentiation may be of great help. For this purpose, we aimed to identify a biomarker panel based on the expression analysis of a small sample of tissue to support the pathological analysis of surgery resection specimens. Given that an aberrant glutamate signaling was identified to drive glioblastoma progression, we focused on glutamate receptors and key players of glutamate homeostasis.

Methods

Based on surgically resected samples from 55 brain tumors, the expression of ionotropic and metabotropic glutamate receptors and key players of glutamate homeostasis were analyzed by RT-PCR. Subsequently, a receiver operating characteristic (ROC) analysis was performed to identify genes whose expression levels may be associated with either glioblastoma or brain metastasis.

Results

Out of a total of 29 glutamatergic genes analyzed, nine genes presented a significantly different expression level between high-grade gliomas and brain metastases. Of those, seven were identified as potential biomarker candidates including genes encoding for AMPA receptors GRIA1, GRIA2, kainate receptors GRIK1 and GRIK4, metabotropic receptor GRM3, transaminase BCAT1 and the glutamine synthetase (encoded by GLUL). Overall, the biomarker panel achieved an accuracy of 88% (95% CI: 87.1, 90.8) in predicting the tumor entity. Gene expression data, however, could not discriminate between patients with seizures from those without.

Conclusion

We have identified a panel of seven genes whose expression may serve as a biomarker panel to discriminate glioblastomas and brain metastases at the molecular level. After further validation, our biomarker signatures could be of great use in the decision making on subsequent treatment regimens after diagnosis.
The value of the malignant subregion-based texture analysis in predicting the Ki-67 status in breast cancer
Authors: Hua Chao , Wenwen Chen , Huijuan Rui , Ting Pan , Jin Zhang
Published: May 2024

Objective

To evaluate the value of the malignant subregion-based texture analysis in predicting Ki-67 status in breast cancer.

Materials and methods

The dynamic contrast-enhanced magnetic resonance imaging data of 119 histopathologically confirmed breast cancer patients (81 patients with high Ki-67 expression status) from January 2018 to February 2023 in our hospital were retrospectively collected. According to the enhancement curve of each voxel within the tumor, three subregions were divided: washout subregion, plateau subregion, and persistent subregion. The washout subregion and the plateau subregion were merged as the malignant subregion. The texture features of the malignant subregion were extracted using Pyradiomics software for texture analysis. The differences in texture features were compared between the low and high Ki-67 expression cohorts and then the receiver operating characteristic (ROC) curve analysis to evaluate the predictive performance of texture features on Ki-67 expression. Finally, a support vector machine (SVM) classifier was constructed based on differential features to predict the expression level of Ki-67, the performance of the classifier was evaluated using ROC analysis and confirmed using 10-fold cross-validation.

Results

Through comparative analysis, 51 features exhibited significant differences between the low and high Ki-67 expression cohorts. Following feature reduction, 5 features were selected to build the SVM classifier, which achieved an area under the ROC curve (AUC) of 0.77 (0.68–0.87) for predicting the Ki-67 expression status. The accuracy, sensitivity, and specificity were 0.76, 0.80, and 0.68, respectively. The average AUC from the 10-fold cross-validation was 0.72 ± 0.14.

Conclusion

The texture features of the malignant subregion in breast cancer were potential biomarkers for predicting Ki-67 expression level in breast cancer, which might be used to precisely diagnose and guide the treatment of breast cancer.
Case report: Simultaneous resections of pulmonary segment and an esophageal leiomyoma during spontaneous ventilation video-assisted thoracoscopic surgery
Authors: Ding Yi , Shan Lei , Li Peichao , Li Ning , Zhang He , Cong Bo , Zhang Hua , Tian Zhongxian , Zhao Xiaogang , Zhao Yunpeng
Published: May 2024

Spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) has rapidly developed in recent years. The application scope is still being continuously explored. We describe a case in which a 40-year-old woman with mixed ground-glass opacity (GGO) and an esophageal leiomyoma successfully underwent simultaneous segmentectomy and leiomyoma resection through spontaneous ventilation video-assisted thoracoscopic surgery. The perioperative course was uneventful. Postoperative pathology revealed minimally invasive adenocarcinoma and esophageal leiomyoma.
Acute hematologic toxicity prediction using dosimetric and radiomics features in patients with cervical cancer: does the treatment regimen matter?
Authors: Yue Haizhen , Li Xiaofan , You Jing , Feng Pujie , Du Yi , Wang Ruoxi , Wu Hao , Cheng Jinsheng , Ding Kuke , Jing Bin
Published: May 2024

Background

Acute hematologic toxicity (HT) is a prevalent adverse tissue reaction observed in cervical cancer patients undergoing chemoradiotherapy (CRT), which may lead to various negative effects such as compromised therapeutic efficacy and prolonged treatment duration. Accurate prediction of HT occurrence prior to CRT remains challenging.

Methods

A discovery dataset comprising 478 continuous cervical cancer patients (140 HT patients) and a validation dataset consisting of 205 patients (52 HT patients) were retrospectively enrolled. Both datasets were categorized into the CRT group and radiotherapy (RT)-alone group based on the treatment regimen, i.e., whether chemotherapy was administered within the focused RT duration. Radiomics features were derived by contouring three regions of interest (ROIs)—bone marrow (BM), femoral head (FH), and clinical target volume (CTV)—on the treatment planning CT images before RT. A comprehensive model combining the radiomics features as well as the demographic, clinical, and dosimetric features was constructed to classify patients exhibiting acute HT symptoms in the CRT group, RT group, and combination group. Furthermore, the time-to-event analysis of the discriminative ROI was performed on all patients with acute HT to understand the HT temporal progression.

Results

Among three ROIs, BM exhibited the best performance in classifying acute HT, which was verified across all patient groups in both discovery and validation datasets. Among different patient groups in the discovery dataset, acute HT was more precisely predicted in the CRT group [area under the curve (AUC) = 0.779, 95% CI: 0.657–0.874] than that in the RT-alone (AUC = 0.686, 95% CI: 0.529–0.817) or combination group (AUC = 0.748, 95% CI: 0.655–0.827). The predictive results in the validation dataset similarly coincided with those in the discovery dataset: CRT group (AUC = 0.802, 95% CI: 0.669–0.914), RT-alone group (AUC = 0.737, 95% CI: 0.612–0.862), and combination group (AUC = 0.793, 95% CI: 0.713–0.874). In addition, distinct feature sets were adopted for different patient groups. Moreover, the predicted HT risk of BM was also indicative of the HT temporal progression.

Conclusions

HT prediction in cervical patients is dependent on both the treatment regimen and ROI selection, and BM is closely related to the occurrence and progression of HT, especially for CRT patients.