bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic and Biophysical Evaluation and Characterization of Cyclic Peptides for Antituberculosis Drug Development Targeting ClpC1
Authors: Vaid Tasneem Murtuza , Demissie Robel , Kwon Youngjin , Shetye Gauri , Tran Thao , Nomani Fatema , Jin Shengnan , Suh Joo-Won , Lee Hanki , Shin Yern-Hyerk , Cui Jinsheng , Oh Dong-Chan , Franzblau Scott G. , Cho Sanghyun , Lee Hyun
Published: December 2024

Natural products and synthetic small molecules have been extensively studied as potential therapeutics against Mycobacterium tuberculosis (Mtb), particularly drug-resistant strains. The caseinolytic protein C1 (ClpC1) has emerged as a promising drug target for combating Mtb, and accurate measurement of its ATPase activity is essential for elucidating the mechanisms of drug candidates. In this study, we optimized a highly sensitive ATPase assay for ClpC1 and compared the enzymatic activity of various constructs, including N-terminal His6-SUMO-tagged, C-terminal His6-tagged, native full-length (FL) ClpC1, and smaller domains. Our results demonstrated that the N-terminal tag significantly impairs ClpC1 activity, whereas the C-terminal tag has no such effect. Additionally, smaller domains exhibited markedly reduced enzymatic activity compared to FL-native ClpC1. Taking the native ClpC1 forward, we tested three natural products—rufomycin (RUF), ecumicin (ECU), and cyclomarin A (CYMA)—and observed varying degrees of ATPase activity enhancement. ECU and five of its analogs were further evaluated, yielding AC50 values consistent with their binding affinities (KD) measured by surface plasmon resonance (SPR). RUF and CYMA exhibited strong KD values of 0.023 µM and 0.006 µM, respectively, and minimal inhibitory concentrations (MICs) of 0.02 µM and 0.094 µM, respectively. However, their ATPase activity enhancement was modest (<93%). In contrast, ECU and its analogs significantly enhanced ATPase activity (up to 830%) despite weaker MICs and KD values compared to RUF and CYMA. These findings suggest that RUF/CYMA and ECU may operate via distinct mechanisms of action, offering valuable insights for the development of ClpC1-targeting therapeutics against tuberculosis.
Urban Furniture Design Strategies to Build Healthy and Inclusive Neighbourhoods
Authors: Rinaldi Alessandra , Viviani Sara , Busciantella-Ricci Daniele
Published: December 2024

Several guidelines provided by European organizations and the World Health Organization, and frameworks in the scientific literature suggest focusing on the built environment for promoting public health as it acts as a promoter of healthy lifestyles. They also highlight the importance of creating healthy conditions for active ageing through spatial and urban furniture solutions that improve overall accessibility, walkability, and independence, by providing supporting products, such as urban furniture for resting and access to quality food and water, as well as equipment for physical activities, including socializing and creating multigenerational connections.
The paper presents the results at the micro scale, relating to urban furniture design, of an action-research, that investigated two representative neighborhoods as case studies of Florence in which the topics of inclusion, proximity and healthy lifestyles were tested, and design strategies and orienting scenarios for a healthy neighborhood were developed.
Semi-structured interviews, co-design workshops, and living labs with citizens, stakeholders and experts provided several needs, problems, opportunities, and potential aspects about the healthy perspective of the neighborhoods.
The results highlight the potential and important role of urban furniture design in promoting a healthy built environment, underlining the strategic role of tangible products as healthy touchpoints to promote healthy lifestyles.
Vestibular Assessment in Infants with Congenital or Early Onset Sensorineural Hearing Loss: Is Neonatal Screening Required?
Authors: Farquhar Lauren , Refaie Amr El
Published: December 2024

Background/Objectives: Children with congenital or early onset sensorineural hearing loss (SNHL) are at a greater risk of vestibular dysfunction (VD), hypothesised to occur from the close embryological relationship between the cochlear and vestibular systems. Even with increasing focus on early detection and rehabilitation through Universal Newborn Hearing Screening Programmes in many countries, few studies have focused on the prevalence and feasibility of vestibular assessment on infant populations. The objectives of this review are to 1. Identify the prevalence of VD infants with congenital or early onset SNHL, 2. Identify which vestibular assessment tests/protocols are conducted on this population, 3. Report sensitivity and specificity values for identified vestibular assessment tests/protocols. Methods: Studies including infants aged 0-12 months, with congenital or early onset SNHL of any laterality, degree and configuration and underwent any method of vestibular assessment. The review adhered to the Joanna Briggs Institute (JBI) guidance and the PRISMA-ScR extension statement. Results: A total of 14 studies were included in the review. All articles reported that infants with congenital or early onset SNHL are at a greater risk of VD, particularly those with bilateral severe-profound SNHL. The cVEMP test was the most frequently identified vestibular assessment tool utilised within this age demographic. Conclusions: Results from the included articles coincide with results from literature assessing older paediatric populations. cVEMPs have been reported to be a feasible, sensitive, and specific screening tool in infants with congenital or early onset SNHL. The prevalence of VD in infants with congenital or early onset SNHL justify further investigation on the feasibility of establishing a pathway for vestibular assessment for all infants referred by UNHS programmes.
Characterization of the Pro-Inflammatory, Regulatory and Anti-Inflammatory Cytokines of Distress Placenta in Different Gestation Times
Authors: Brikune Elizabete , Junga Anna , Brikune Jana , Pilmane Māra
Published: December 2024

Pregnancy represents a delicate immunological balance, with cytokines playing pivotal roles in regulating maternal-fetal interactions. Distress acuta is associated with persistent inflammation that may impact placental function and pregnancy outcomes. Thus, this study aims to analyze the expression and distribution of key cytokines – IL-1α, IL-2, IL-4, IL-6, IL-7, IL-8, and IL-10 – in distressed placental tissues across three gestational periods: 28th, 31st, and 40th weeks. Placental samples from 15 participants were examined using immunohistochemistry, semi-quantitative evaluation, and non-parametric statistical methods. The findings revealed persistent high activity of IL-1α across all gestational periods, signifying its role in sustaining inflammation. IL-2 activity declined with advancing gestation, indicating adaptive immune modulation, while IL-7 and IL-8 showed sustained activity irrespective of placental aging, underscoring their roles in inflammation and immune response. Anti-inflammatory cytokines IL-4 and IL-10 were minimally expressed, suggesting limited anti-inflammatory regulation in distress conditions. Conversely, IL-6 demonstrated consistent expression, highlighting its regulatory function in maintaining placental integrity. Correlation analysis revealed intricate interactions among cytokines, reflecting a complex regulatory network essential for placental homeostasis during distress acuta.
Ferroptosis Transcriptional Regulation and Prognostic Impact in Medulloblastoma Subtypes Revealed by scRNA-seq
Authors: Desterke Christophe , Fu Yuanji , Bonifacio-Mundaca Jenny , Monge Claudia , Pineau Pascal , Mata-Garrido Jorge , Francés Raquel
Published: December 2024

Medulloblastoma (MB) is the most common malignant brain tumor in children, typically arising during infancy and childhood. Despite multimodal therapies achieving a response rate of 70% in children older than 3 years, treatment remains challenging. Ferroptosis, a form of regulated cell death, can be induced in medulloblastoma cells in vitro using erastin or RSL3. Using two independent medulloblastoma RNA-sequencing cohorts (MB-PBTA and MTAB-10767), we investigated the expression of ferroptosis-related molecules through multiple approaches, including Weighted Gene Co-Expression Network Analysis (WGCNA), molecular subtype stratification, protein-protein interaction (PPI) networks, and univariable and multivariable overall survival analyses. A prognostic expression score was computed based on a cross-validated ferroptosis signature. In training and validation cohorts, regulation of the ferroptosis transcriptional program distinguished the four molecular subtypes of medulloblastoma. WGCNA identified nine gene modules in the MB tumor transcriptome; five correlated with molecular subtypes, implicating pathways related to oxidative stress, hypoxia, and trans-synaptic signaling. One module, associated with disease recurrence, included epigenetic regulators and nucleosome organizers. Univariable survival analyses identified a 45-gene ferroptosis prognostic signature associated with nutrient sensing, cysteine and methionine metabolism, and trans-sulfuration within one-carbon metabolism. The top ten unfavorable ferroptosis genes included: CCT3, SNX5, SQOR, G3BP1, CARS1, SLC39A14, FAM98A, FXR1, TFAP2C, and ATF4. Patients with a high ferroptosis score showed worse prognosis, particularly in G3 and SHH subtypes. The PPI network highlighted IL6 and CBS as unfavorable hub genes. In a multivariable overall survival model, which included gender, age, and molecular subtype classification, the ferroptosis expression score was validated as an independent adverse prognostic marker (hazard ratio: 5.8; p-value = 1.04 × 10⁻⁹). This study demonstrates that regulation of the ferroptosis transcriptional program is linked to medulloblastoma molecular subtypes and patient prognosis. A cross-validated ferroptosis signature was identified in two independent RNA-sequencing cohorts, and the ferroptosis score was confirmed as an independent and adverse prognostic factor in medulloblastoma.
Intracranial Hemorrhage in Childhood Hemophilia Patients
Authors: Ay Tuncel Defne , Sasmaz Hatice Ilgen , Antmen Bulent
Published: December 2024

ABSTRACT Childhood hemophilia, a hereditary bleeding disorder predominantly affecting males, arises due to mutations in the genes encoding clotting factors VIII or IX. Intracranial hemorrhage represents a significant and life-threatening complication in pediatric patients with hemophilia. The incidence of intracranial hemorrhage in children with hemophilia, although relatively low, is notably higher compared to the general pediatric population. In this study, the objective is to examine patients with hemophilia who have experienced intracranial hemorrhage retrospectively. This study is a multicenter, retrospective analysis using data from three tertiary care centers in a provincial city in Turkey. Data were obtained from the participants' hospital records. The presence of inhibitors in the participants and the prophylaxis used against them were included in the analysis. Trauma history was queried, with types of traumas examined, including traffic accidents, falls, and a traumatic vaginal delivery. The duration and causes of complaints among the participants were investigated. The causes of complaints were categorized as fever, hematoma, convulsions, loss of consciousness, and hemiparesis. The participants' physical examination findings were classified as fever, hematoma, and loss of consciousness. The duration of hospital stays was evaluated. The hemorrhage location was classified into five groups: parenchymal, subdural, scalp, subarachnoid, and multiple hemorrhagic foci. The recurrence of bleeding, the need for transfusion, surgical intervention, and mortality were also examined. A significant difference was identified between the participants' survival rates and age variables, transfusion in < 36 months. Nine participants were spontaneous intracranial bleeding, two experienced cranial trauma as a result of traffic accidents, and 25 participants were exposed to head trauma due to falls. Of the remaining individuals, one suffered head trauma from a severe impact, and one did cranial trauma following a traumatic vaginal delivery. Fourteen participants required transfusion, and three underwent surgical intervention. According to the results of the statistical analyses, the variables Factor Level, Physical Examination Findings, Transfusion, Recurrent Bleeding, Inhibitor, and Prophylaxis were found to affect survival significantly. No significant relationship was determined between the other analyzed variables and survival. In our study, five of the participants examined have died. Accordingly, the mortality rate identified in our study is 13.1%.
The FAbry STabilization indEX Is Insufficient for Evaluating the Effectiveness of Enzyme Replacement Therapy for Pediatric Fabry Disease
Authors: KOGA Nobuhiko , INOUE Takahito , UESUGI Noriko , NAGAMITSU Shinichiro
Published: December 2024

Background: Fabry disease (FD) is a progressive disorder characterized by a decrease or deficiency in α-galactosidase enzyme activity. The FAbry STabilization indEX (FASTEX) scores FD symptoms and measures clinical deterioration as the score increases. However, the effectiveness of FASTEX for evaluating pediatric FD has not yet been examined. Methods: We conducted FASTEX scoring on 5 cases of FD receiving enzyme replacement therapy at our department by September 2022 (1 classical-type male, 2 late-onset males, and 2 heterozygous females). We performed FASTEX scoring before and after the initiation of treatment, defining a change in score of 20% or less from the baseline as clinically unchanged. Results: FASTEX did not show an increase in scores during the treatment course in the late-onset males and heterozygous females. FASTEX in the classical-type male only increased from 0 to 5 points during treatment, but did not show a temporal increase and, thus, he was judged to be clinically unchanged. Conclusion: FASTEX may not be sufficient to evaluate treatment effects in pediatric FD cases. New evaluation methods for pediatric cases are required, particularly for those detected through newborn screening.
Wnt Pathway Targeted Therapy in GI Cancers: Integrating Benchside Insights with Bedside Applications
Authors: Nayak Anirudh , Streiff Hannah , Adekoya Oluwabomi Oluwatomi , Gonzalez Ivan , Silva Itzcoatl , Shenoy Anitha Kota
Published: December 2024

The Wnt signaling pathway is critical in the onset and progression of gastrointestinal (GI) cancers. Anomalies in this pathway, often stemming from mutations in critical components such as adenomatous polyposis coli (APC) or β-catenin, lead to uncontrolled cell proliferation and survival. In the case of colorectal cancer, dysregulation of the Wnt pathway drives tumor initiation and growth. Similarly, aberrant Wnt signaling contributes to tumor development, metastasis, and resistance to therapy in other GI cancers, such as gastric, pancreatic, and hepatocellular carcinomas. Targeting the Wnt pathway or its downstream effectors has emerged as a promising therapeutic strategy for combating these highly aggressive GI malignancies. Here, we review the dysregulation of the Wnt signaling pathway in the pathogenesis of GI cancers and further explore the therapeutic potential of targeting the various components of the Wnt pathway. Furthermore, we summarize and integrate the preclinical evidence supporting the therapeutic efficacy of potent Wnt pathway inhibitors with completed and ongoing clinical trials in GI cancers. Additionally, we discuss the challenges of Wnt pathway targeted therapies in GI cancers to overcome these concerns for effective clinical translation.
Roles of Whole Genome Sequencing in Determining Transmission, Risk Factors Associated with Carbapenem-Resistant Organisms at a Vietnam HealthCare Center of Orphaned Children, Vietnam
Authors: Nguyen Kim Van , Noisumdaeng Pirom , Ivanovitch Maj Katiya , Athan Eugene , Croft Larry , Nguyen Phuong Toai , Nguyen Huu Phuc Pham
Published: December 2024

Antimicrobial resistance is a most concerning public health issue in Vietnam due to antibiotic-resistant Gram-negative bacteria, including Carbapenem-resistant organisms (CROs), which might appear in remote areas in Vietnam. So, at this center, we performed a cross-sectional study and collected fecal samples from human subjects (20 healthcare workers (HCWs) and 67 residents) and 175 environmental samples, with rectal and environment swabs, as study data for this study, from September 2022 to December 2022. We conducted the microbiological testing, including the MELAB-Chromogenic-CARBA-agar plates, blood-agar plates, and BD PhoenixTM Automated Microbiology System to screen, isolate, and identify bacterial species and phenotypic tests for antimicrobial susceptibility of carbapenem-resistant bacteria, and the whole genome sequencing for 12 CROs chosen to confirm the CRO transmission between HCWs and residents. The study findings showed the prevalence and risk factors associated with CRO colonization were detected in HCWs, residents, and the environment in the Center of Care and Protection of Orphan Children. CRO transmission happened between HCWs and residents detected with WGS analysis. So, whole genome sequencing (WGS) plays a significant role in CRO control and prevention and reduces CRO transmission/ colonization in this center and other healthcare settings.
Building Acceptance Through Parents' Self-Efficacy In Supporting Children With Special Needs Philosophical Studies A Literature Review
Authors: Yusiana Maria Anita , Pandin Moses Glorino Rumambo , Yusuf Ah.
Published: December 2024

Introduction: Parental acceptance of children with special needs is an important factor that influences child development and family well-being. However, many parents have difficulty accepting their child's condition, which can have a negative impact on interactions and support. This study aims to explore the relationship between parents' self-efficacy and their acceptance of children with disabilities and analyze it through philosophical studies.Research method: this research uses a literature review using the PICOS framework. Articles were searched from 3 databases namely Scopus, Sciencedirect, Sage. The keywords used in the literature search are self-efficacy AND parental acceptance AND philosophical approach, especially existentialism. The search was limited to publications in 2019-2024, complete articles. Starteginyang used to search for articles using the PICOS framework, then selected using the PRISMA diagram and obtained six articles. Results: The results of the analysis show that parents with high levels of self-efficacy tend to be more able to accept and adapt to the conditions of children with special needs, which has a positive impact on their support and interactions. In addition, the existentialism philosophy approach provides insight into the search for meaning and understanding in the face of challenges faced by parents.Conclusion: this study confirms that increasing parental self-efficacy can be an effective strategy to build better acceptance of children with special needs, which in turn can improve the quality of support provided to children. By understanding and meeting the specific needs of parents, we can promote better outcomes for families with children with special needs.
Characterization of the Prevalence and Antibiotic Resistance among Staphylococcus species in an Exercise Facility in Central Kentucky, USA
Authors: Kiborus Lilian Jeptoo , Altheide S. Travis , Marion Jason W.
Published: December 2024

The spread of methicillin-resistant Staphylococcus aureus (MRSA) in community settings, including fitness/exercise centers, remains relevant for public health. MRSA, a cause for severe infections in some, can be transmitted through shared equipment and skin contact. Understanding its prevalence and the frequency of antibiotic resistance in such environments can be useful for informing hygiene and intervention strategies. For this investigation, multiple environmental swabs were collected from 14 different sites within a fitness facility, including equipment and locker rooms. Samples were collected to characterize the prevalence of staphylococci (including MRSA), E. coli, and carbapenem-resistant enterococci (CRE). Isolated colonies were identified biochemically and evaluated for antibiotic resistance. Logistic regression was applied to assess risk across different surfaces. Among 42 samples, the highest prevalence of Staphylococcus spp. was found on locker room surfaces. S. aureus was prevalent on locker room floors and benches. Non-S. aureus species, such as S. saprophyticus and S. haemolyticus, were common. Resistance to oxacillin and penicillin was widespread, particularly among non-S. aureus species. E. coli were detected once, and CRE were not detected. Fitness center surfaces can harbor staphylococci, including MRSA. This facility, and probably others, have notable antibiotic resistance among other staphylococci. Hygiene improvements, including personal hygiene actions, are essential for reducing transmission risks.
Cloud-Based License Plate Recognition: A Comparative Approach Using YOLO Versions 5,7, 8 and 9 Object Detection
Authors: Asaju Christine Bukola , Owolawi Pius Olawale , Tu Chuling , Van Wyk Etienne
Published: December 2024

Cloud-based License Plate Recognition (LPR) systems have emerged as essential tools in modern traffic management and security applications. Determining the best approach remains paramount in the field of computer vision. This study presents a comparative analysis of various versions of the YOLO (You Only Look Once) object detection models, namely YOLO 5, 7, 8 and 9, applied to LPR tasks in a cloud computing environment. Using live video, We performed experiments on YOLOv5, YOLOv7, YOLOv8, and YOLOv9 models to detect number plates in real-time. According to the results, YOLOv8 reported the most effective model for real-world deployment due to its strong cloud performance. It achieved an accuracy of 78\% during cloud testing, while YOLOv5 showed consistent performance with 71\%. YOLOv7 performed poorly in cloud testing (52\%), indicating potential issues, while YOLOv9 reported 70\% accuracy. This tight alignment of results shows consistent, although modest, performance across scenarios. The findings highlight the evolution of the YOLO architecture and its impact on enhancing LPR accuracy and processing efficiency. The results provide valuable insights into selecting the most appropriate YOLO model for cloud-based LPR systems, balancing the trade-offs between real-time performance and detection precision. This research contributes to advancing the field of intelligent transportation systems by offering a detailed comparison that can guide future implementations and optimisations of LPR systems in cloud environments.
Automata: Completeness, Expressibility, Application
Authors: Aleshin Stanislav Vladimirovich , Babin Dmitry Nikolaevich , Chasovskikh Anatolii Aleksandrovich
Published: December 2024

The study of expressive properties in classes of discrete control systems has become the most important direction of development of the Russian school of cybernetics, one of the founders of which is Sergey Vsevolodovich Yablonsky. Of particular interest are the classes of finite automata widely used, in particular, for modeling integrated circuits. The paper provides an overview of the results of studies of the expressive properties of automata obtained within the framework of the scientific school of S.V. Yablonsky and his associates since its foundation.
Entre lutas e saberes
Authors: Araújo Aline Praxedes , Bezerra da Silva Severino , Dos Santos Wanderley Kamila Karine
Published: December 2024

Este artigo analisa as práticas educativasdas egressas do curso de Pedagogia do Pronerana Universidade Federal da Paraíba,em parceria com a Comissão Pastoral daTerra (2015-2019). Focando as narrativasbiográficas, investiga como as experiênciasno ensino superior influenciaram as formaçõesprofissionais e pessoais das egressas.No campo teórico, centramos nossasanálises na Educação Popular e no debatedecolonial de gênero. Dialogamos com autorase autores como Brandão (1994), Freire(2018), Lugones (2014), Mejía (1994),entre outras e outros. Os procedimentosmetodológicos incluem pesquisa bibliográficae documental e entrevistas semiestruturadas.Os resultados indicam que oacesso e a permanência no ensino superiorpara mulheres camponesas resultaram nofortalecimento de sua identidade campo nesa. No tocante ao contexto profissional,observamos educadoras comprometidascom uma Educação do Campo pública ede qualidade.
Relato de experiência do ensino de história indígena nos anos finais do fundamental
Authors: Gabriel dos Santos Silva Pedro
Published: December 2024

O objetivo do presente trabalho gira emtorno de expor o desenvolvimento de oficinaspara ensino de História Indígena,nos anos finais do ensino fundamental,com turmas de sexto a nono ano, em umaescola pública do município de São Gonçalodo Amarante-RN, com a finalidadede combater e problematizar estereótiposhistoricamente construídos sobre as comunidadese a cultura indígena no Brasil.Para tanto, foram utilizados os parâmetrosde ensino de História previstos pela BaseNacional Comum Curricular (BNCC), emque foram priorizados os conhecimentos ecompetências referentes a uma educaçãoplural, voltados para a valorização da sociodiversidadeétnica que forma a sociedadebrasileira contemporânea.
Em roda com intelectuais negras/os para pensar uma teoria do racismo “à brasileira”
Authors: Nascimento Mariana Galvão , Silva Renato Izirodo da
Published: December 2024

Este ensaio consiste em uma reflexão teórica sobre a experiência do racismo no Brasil a partir das reflexões de intelectuais negras/os sobre o fenômeno do racismo à brasileira, paralelamente às modalidades francesa e estadunidense, para citar dois exemplos correlatos, mas diferentes. Partimos da premissa de que uma compreensão teórica da experiência do racismo ganha força com uma formulação conceitual baseada em uma abordagem epistemológica afrorreferenciada. Defenderemos a hipótese de que uma compreensão contemporânea da experiência do racismo construída histórica e socialmente na esteira coletiva dos intercâmbios da intelectualidade negra transatlântica e amefricana.
Metastasis of WHO Grade II Meningioma With Subsequent Pathological T12 Fracture
Authors: Zhang Helen , Hardacker Kyle , Alsoof Daniel , Balmaceno-Criss Mariah , Daher Mohammad , Kuris Eren , Diebo Bassel G. , Daniels Alan H. , McCluskey Leland C.
Published: December 2024

Case:

A 64-year-old woman with a history of World Health Organization Grade II (Ki-67 20%) atypical meningioma presented with T12 vertebral body burst fracture as a complication of metastatic meningioma (SSTR2+). Following disease progression, decompression surgery and stabilization through T10-L2 posterior thoracolumbar instrumented fusion was performed.

Conclusion:

This is one of few documented cases of spinal metastatic meningioma causing pathological fracture and the first to detail surgical management and longitudinal follow-up. Applying the neurologic, oncologic, mechanical, and systemic decision framework to this rare presentation, the patient was indicated for the selected surgical approach, yielding short-term improvement of patient outcome and neurologic deficit.
Apego y síntomas emocionales en familiares de adolescentes con talla baja
Authors: Lacomba-Trejo Laura , Casaña-Granell Sara , Montoya-Castilla Inmaculada , Pérez-Marín Marián
Published: December 2024

Caring for an adolescent child with a medical condition such as short stature (TB) is associated with emotional symptoms. Sociodemographic factors and secure attachment may buffer them. The aim was to study factors related to emotional symptoms in caregivers of adolescents with TB. A total of 157 caregivers of adolescents with TB participated. We assessed sociodemographic variables, anxiety, depression and attachment. Many had anxious symptoms (46.90%), depressive symptoms (17.50%) and emotional distress (14.40%). Secure attachment, the presence of fewer children, the absence of chronic conditions in other children, and a lesser affectation of the child's height were associated with less symptomatology. It is important to attend to the family in the process of assessment and treatment of the disease.
RETRACTED: Weighing sustainability potentials: A DEMATEL analysis of interrelationships in smart manufacturing technologies
Authors: Leutheuser Viktoria , Müller Julian Marius , Voigt Kai-Ingo
Published: December 2024

The authors have requested that this preprint be removed from Research Square.
Diffusion Smart-seq3 of breast cancer spheroids to explore spatial tumor biology and test evolutionary principles of tumor heterogeneity
Authors: Cougnoux Antony , Mahmoud Loay , Johnsson Per , Gsell Louise , Rosenbauer Jakob , Eroglu Alper , Sandberg Rickard , Hausser Jean
Published: December 2024

Combining 3D cultures such as tumor spheroids and organoids with spatial omics holds great potential for tissue biology and cancer research. Yet, this potential is presently limited by technical and financial challenges of spatial omics methods and 3D cultures. To address this, we combine dye diffusion, the Smart-seq3xpress protocol for deep single-cell gene expression profiling, and dedicated probabilistic inference methods into diffusion Smart-seq3 (Smart-seq3D), to reveal the transcriptome of single cells along with their position along the core-periphery axis of spheroids. Applying Smart-seq3D to triple-negative breast tumor spheroids identifies thousands of spatial genes and reveals continuous, ungated spatial gene expression. Spatial gene and pathway expression patterns suggest biologies specific to spheroid regions, which we validate by immunostainings and pharmacological interventions. We use the Smart-seq3D data to test evolutionary principles of spatial tumor heterogeneity. Finally, we characterize aspects of tumor heterogeneity captured by 3D spheroids that are missing from 2D cultures but found in tumors in vivo. Smart-seq3D can offer a cost-efficient approach to explore how cells adapt their transcriptome to different micro-environments, reveal spatial determinants of drug resistance and could serve to characterize spatial interactions between cancer and stromal/immune cells in 3D co-cultures.
A 4-plex droplet digital PCR (ddPCR) to quantity four food-borne pathogenic bacteria simultaneously
Authors: Sun Xueqi , Xiao Jian , Wei Haiyan , Chen Kai , Huang Zhishen , Lao Jiaqian , Lin Xiuming , Liang Meidan , Zeng Shanmei
Published: December 2024

To establish a 4-plex ddPCR method for quantitatively detecting the four major pathogenic bacteria: Salmonella, Staphylococcus aureus, Listeria monocytogenes, and Bacillus cereus in instant food simultaneously, primers, probes, and PCR conditions were optimized. For the 4-plex ddPCR assay, four target pathogens demonstrated a good linear correlation to the readouts (r2>0.999). The linear dynamic ranges were: 33-21504 copies/20µL for Salmonella, 28-18404 copies/20µL for Staphylococcus aureus, 25-27012 copies/20µL for Listeria monocytogenes and 15-15560 copies /20µL for Bacillus cereus. The relative standard deviations (RSD) at different concentrations of the target pathogens were all less than 25% (n = 5) indicating the good repeatability of the assay. The detection limits were 8 copies/20µL (Salmonella), 7 copies/20µL (Staphylococcus aureus), 9 copies/20µL (Listeria monocytogenes) and 7 copies/20µL (Bacillus cereus). The established 4-plex ddPCR assay was evaluated in parallel with the classical plate colony-counting method to detect the target pathogens in the four types of simulated samples. The results from the two assays are similar with deviations less than 9%. Still, the PCR assay appears superior to the plate method, evidenced by the short turnaround time, lower detection limit, and robust reproducibility.
An Island that has been an Island twice: How and why small volcanic ocean islands collapse and move vertically up and down
Authors: Marques Fernando O. , Ribeiro Luísa P. , Hübscher Christian , Costa Ana C.G. , Hildenbrand Anthony
Published: December 2024

Mass controls two major processes in volcanic islands: large-scale collapse and vertical movements. Therefore, large islands like Hawaii are gradually subsiding and have undergone massive landsliding. What if the mass is much smaller, and there is good evidence that the vertical movement is more complex than simple loading-related subsidence? Here, we show that small volcanic islands, seemingly stable because of the small mass, can undergo sector collapses that can affect the vertical movement of the island. Santa Maria Island (Azores) is ca. 170 times smaller than Hawaii; however, it has collapsed more than once, as inferred from new onshore and marine geophysical data. From the vertical distribution of submarine and subaerial lavas, we can infer a complex subsidence and uplift history (seamount-island-seamount-island), which is most likely the consequence of alternating volcanic construction and large-scale collapses. Given the age difference between Santa Maria and the underlying oceanic crust, the island likely sits on several hundred meters of marine sediments that could behave as a weak layer (detachment) under shear. We evaluate the likely collapse mechanism by numerical modelling and conclude that small volcanic islands can collapse when both the edifice and its substrate are weak. The proximity of Santa Maria to the East Azores Fault, active during the volcanic lifetime of Santa Maria, may point to the trigger mechanism of the flank collapses. The inferred instability factor, a weak substrate, could be responsible for similar evolutions in other volcanic ocean islands sitting on sediments overlying the igneous oceanic crust.
Development and validation of a minimal SNP genotyping panel for the differentiation of Cannabis sativa chemovars
Authors: Cull Alex , Joly David L.
Published: December 2024

Background
Due to its previously illicit nature, cannabis had not fully reaped the benefits of recent innovations in genomic plant science. However, Canada’s legalization of cannabis in 2018 triggered significant new demand for robust genotyping tools to assist breeders in meeting consumer demands. While most molecular marker-based research on cannabis has focused on screening for traits of agronomic value, more recent research has sought to use molecular markers to differentiate between cannabis cultivars.
Results
In this study, we have conducted whole genome sequencing of 32 cannabis chemovars, mined the sequencing data for SNPs, developed a reduced SNP genotyping panel to discriminate between sequenced chemovars, then validated the 20-SNP panel using DNA from the sequenced varieties and tested the assays on commercially available cannabis products. The assay conversion rate was high in DNA extracted from fresh plant material and middling in DNA extracted from commercial samples. However, called genotypes were internally consistent, highlighting discrepancies between genotypes predicted using sequencing data and observed using genotyping assays. The primary contributions of this work are to clearly document the process used to develop this genotyping panel and outline improvements and goals for future iterations of PCR-based, minimal SNP panels to enable efficient development genotyping tools to identify and screen cannabis varieties.
Conclusions
Our key recommendations are to leverage higher read length paired-end short-read technology; conduct in-depth pre- and post-processing of reads, mapping, and variant calling data; integrate trait-associated loci to develop multi-purpose panels; use iterative approaches for in vitro validation; and integrate redundancy to account for errors throughout the pipeline and the effects of irradiation sterilization on cannabis DNA extracted from commercially available dried flower samples.
Association of Oxidative Balance Score with chronic constipation and diarrhea among adult men and women:Findings from the National Health and Nutrition Examination Survey(2007-2010)
Authors: Cao Yaoling , Yang Zhihao , Tang Qinqing
Published: December 2024

Objective
Chronic constipation and diarrhea are prevalent functional gastrointestinal disorders. Various factors related to diet and lifestyle contribute to functional bowel disorders. We aimed to examine the association between Oxidative Balance Score(OBS) and chronic constipation and diarrhea among US adult men and women.
Methods
A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey covering the years 2007 to 2010. Altogether, 4,462 subjects were enrolled in our study. The independent variable is the OBS scoring based on 20 types of dietary and lifestyle components. We conducted binary logistic regression, subgroup analysis by sex, and used restricted cubic spline (RCS) to illustrate the relationship between OBS and abnormal bowel health.
Results
In the fully-adjusted Model 3, the odds ratio (OR) with a 95% confidence interval for OBS in the fourth quartile was 0.302 (0.113, 0.808) (p for trend < 0.001) in men with constipation, compared to the third quartile. Similarly, the incidence of of diarrhea in women varied significantly across OBS in the third quartile [OR: 0.422 (0.218, 0.816), P = 0.010] and the fourth quartile [OR: 0.387 (0.178, 0.839), P = 0.016] (P for trend < 0.001). A negative linear trend between OBS and constipation is identified by RCS, with a p-value for non-linear relations greater than 0.05.
Conclusion
In conclusion, low OBS is negatively related to the risk of constipation in males and diarrhea in females.
Suppressed ammonia emission through the circulation of composted liquid fertilizer from swine waste liquid discharge system
Authors: Lee Sang-Ryong , Kim Gyuwon
Published: December 2024

Ammonia (NH3) emissions from animal feeding operations (AFOs) contribute significantly to the total ammonia inventory, causing problems ranging from discomfort for nearby residents to forming particulate matter precursors like NH4NO3 and (NH4)2SO4. Reducing NH3 emissions from AFOs is crucial and requires the implementation of improved manure management systems. In South Korea, a liquid fertilizer circulation (LFC) system has been adopted in the swine industry to convert manure waste into usable fertilizer. However, enhanced NH3 emissions due to microbial activity, particularly anaerobes in swine pit slurry, have been observed. The efficiency of NH3 emission reduction from the LFC system, particularly under controlled variables such as pH, total ammonium nitrogen (TAN), temperature, ion activity, and turbulence, has not been thoroughly investigated. This study evaluated slurry (SL) and liquid fertilizer (LF) from four farms, mixed in three different ratios (SL:LF-7:3, 5:5, and 3:7). These mixtures were tested in a simple-flow Teflon-lined chamber equipped with scrubbers for NH3 collection. Results indicated that swine pit liquid mixed with LF from the LFC system significantly reduced NH3 emissions, likely due to the dilution effect and the bacterial activities that mitigate NH3 emissions in swine slurry.
Cobalt oxide-Zinc oxide nanocatalysts loaded on activated carbon for the photocatalytic degradation of methylene blue dye in water
Authors: Dinka Waktola Fite , Regasa Melkamu Biyana
Published: December 2024

Water contamination with organic dyes like methylene blue (MB) becomes among the main issues at the present time owing to their carcinogenicity and toxic nature towards ecology and human health. Thus, the removal of MB from water using adsorption-photocatalytic degradation method become promising due to its potential to convert this contaminant into non-harmful products. Wastewater containing MB micropollutants can be treated by photocatalytic degradation that involves the application of light and a photocatalyst to break down this dye into less harmful substances. Here, we report cobalt oxide-Zinc oxide (Zn/Co3O4) binary nanocomposite supported on the activated carbon (AC) phoyocatalyst was prepared from the renewable agricultural solid waste (coffee husk) to break down MB in water bodies. The photocatalyst’s optical band gap, average crystalline size and functional groups were characterized by using UV-vis, XRD and FTIR techniques, respectively. The adsorption-photocatalytic degradation of the MB was studied at the optimum experimental parameter values of pH 10, initial concentration of dye of 10 mg/L, catalyst dose of 80 mg and contact time of 120 minutes. Under optimized conditions, the photocatalytic degradation efficiency of MB is 96.16% for ZnO/Co3O4/AC (1:2:2 mass ratios). Furthermore, the light assisted catalytic degradation of MB revealed that the use of AC as support for ZnO/Co3O4 greatly improved the overall performance of the nanocatalyst against MB. This implies that the photocatalytic activities based on the ZnO/Co3O4/AC nanocomposite showed better photo-catalytic efficiency for the target MB dye. The prepared nanocatalyst is renewable and promising for further applications in the future.
A short-term load forecasting framework for air conditioning system based on model stacking
Authors: Liu Tianjie , Jiao Wenling , Huang Zhiwei , Yu Jianting , Zhang Xin , Li Luling
Published: December 2024

Accurate short-term air conditioning load forecasting is very important for controlling air conditioning energy consumption, and is also a requisite for realizing intelligent control of air conditioning units. This paper proposes a short-term load forecasting framework for air conditioning based on the concept of model stacking, which combines six mature machine learning models, including Lasso regression, Ridge regression, Random Forest, Support Vector Regression, eXtreme Gradient Boosting and Long Short-Term Memory, and trains new prediction models through model stacking. In order to realize the short term forecast function of air conditioning load, this paper presents a complete forecast framework, which includes operational procedures for feature screening, algorithm hyperparameters optimization, and cross stacking of prediction models. A real air conditioning system is employed for prediction analysis, the prediction results showed that 28 out of 36 control simulations achieved better prediction accuracy, with an average increase in R2 of 6.4%. Notably, simpler submodels in the meta-model yield better results in model stacking, whereas complex coupling models as the meta-model may degrade performance. These findings provide insights into implementation of model stacking and selecting the meta-model for short-term air conditioning load forecasting.
Sub-nanometer Alloyed Clusters Sustain High Productivity in Propane Dehydrogenation
Authors: He Qian , Lu Shangchen , tang Yaxin , Yao Bingqing , Xi Shibo , Lim Kang Hui , Xu Chaokai , Du Yankun , Fu Xingjie , Tan Shengdong , Zhao Binbin , Luo Wenhao , Wade Chalres , Ma Lu , Dai Sheng , Kawi Sibudjing , Yan Ning , Lu Jiong , Chen Wei , Luo Guangfu
Published: December 2024

Propane dehydrogenation (PDH) processes typically operate at low weight-hourly space velocities (WHSV) of around 10 h⁻¹ to ensure catalyst stability, which however limits propylene productivity to around 0.1 molC3H6·gcatalyst-1·h-1 or less. Here, we report well-controlled sub-nm alloyed PtSn clusters that can sustain propylene productivities about an order of magnitude better when operated at high propane WHSVs. At 165 h⁻¹, the catalyst achieved about 1 molC3H6·gcatalyst-1·h-1 for over 300 hours, with >99% propylene selectivity and a low deactivation rate of approximately 0.002 h⁻¹. Furthermore, the spent catalyst can be fully regenerated using simple air calcination. The clusters themselves have dynamic structures, which, along with their small size and complex coordination environment, allow Pt sites to access a broader range of electronic configurations. This is likely to provide the PDH reaction with a wider energy landscape to navigate, helping to surpass the activity-stability trade-offs in conventional catalysts.
Robust Fuzzy Dynamic Integrated Environmental-Economic-Social Scheduling Considering Demand Response and User’s Satisfaction with Electricity Under Multiple Uncertainties
Authors: ZHANG Hong , Qianwei XI , Lei CHEN , Yong MIN , Xiongxiong FAN , FANG Wenjin , Nan TIAN , Fei XU
Published: December 2024

Aiming at the problems that the uncertainty modeling process of price-based demand response is oversimplified, inconsistent for change pattern of error, and the reliability in user’s comprehensive satisfaction is neglected in the optimal scheduling for power system under multiple uncertainties, integrated factors of economy, environment and society, a multi-objective robust fuzzy optimal scheduling model considering power demand response and user’s comprehensive satisfaction with electricity under multiple uncertainties is proposed. On the basis of analyzing the operation mechanism of the multi-source system and the characteristics of multiple uncertainty sources, the robust theory is used to construct power output model of wind and photovoltaic (PV), and the fuzzy theory is used to construct power demand response model. Taking the lowest comprehensive operation cost as the economic objective, the smallest emissions of CO2 and atmospheric pollutants as environmental objective and the largest user’s comprehensive satisfaction with electricity as the social objective, based on the robust fuzzy theory, the multi-objective uncertainty optimal scheduling model is constructed, which is transformed into deterministic model and then solved by intelligent optimization algorithm. Based on the improved IEEE-39 node system to verify the validity and superiority of the price-based demand response uncertainty modelling method and multiple uncertainty modelling method in this paper, as well as the reasonableness and necessity for considering the reliability in the user’s comprehensive satisfaction with electricity and the multiple uncertainties in power system optimal scheduling.
Physicochemical properties and biological interaction of calcium silicate-based sealers - in vivo model
Authors: Janini Ana Cristina Padilha , Moraes Brenda Fornazaro , Pelepenko Lauter Eston , Santos Victor Augusto Benedicto dos , Barros-Costa Matheus , Malosá Gabriela Fernanda , Batista Fábio Roberto Souza , Meira Juliana Aguiar Silveira , Matsumoto Mariza Akemi , Bessa Thiago , Filho Gaspar Darin , Neto Francisco Haiter , Gomes Brenda P. F. A. , Marciano Marina Angélica
Published: December 2024

Objectives: To investigate volumetric changes, in vivo biocompatibility, and systemic migration from eight commercial materials in paste/paste, powder/liquid, and pre-mixed forms.
Material and Methods: After characterisation, tubes were implanted in Wistar rats’ alveolar bone and subcutaneous tissues. Micro-CT evaluated volumetric changes pre/post 30 days of implantation. Histological and immunohistochemistry analyses assessed biocompatibility. Kidney samples underwent spectrometry (ICP-MS) for tantalum, tungsten and zirconium. Statistical analysis determined normality and significance (p < 0.05).
Results: Characterisation revealed calcium, silicon, and radiopacifiers in the materials. Volumetric changes showed greater alteration in subcutaneous tissues than alveolar bone; BioRoot RCS and MTApex (powder/liquid) were most stable. Histological analysis indicated intense inflammation for AH Plus Jet, moderate for others; IL-10 was marked positively for all materials. Unexpectedly, AH Plus Jet had an 18-fold higher tungsten and a 37-fold higher zirconium mass fraction in kidneys versus controls, while tantalum showed lower accumulation patterns.
Conclusion: Root canal filling materials’ responses varied by implantation site and form, demonstrating acceptable biocompatibility. Tantalum and zirconium oxide radiopacifiers appear systemically safe; tungsten-based radiopacifiers are unsuitable due to metal accumulation risks.
Clinical Relevance: This study highlights the need for further in vivo studies on endodontic sealers’ chemical, biological, and physical behaviors and their systemic migration.