bluuebunny/crossref_metadata_2025 huggingface dataset:
Oblique Line Scan Illumination Enables Expansive, Accurate and Sensitive Single Protein Measurements in Solution and in Living Cells
Authors: Anderson Daniel , Driouchi Amine , Bretan Mason , Davis Brynmor , Heckert Alec , Seeger Markus , Silva Maité Bradley , Forrest William , Hsiung Jessica , Tan Jiongyi , Yang Hongli , McSwiggen David , Song Linda , Sule Akshay , Abaie Behnam , Conroy Brianna , Elliott Liam , Gonzalez Eric , Ilkov Fedor , Isaacs Joshua , Labaria George , Lagana Michelle , Larsen DeLaine , Margolin Brian , Nguyen Mai , Rine Jeremy , Tang Yangzhong , Vana Martin , Wilkey Andrew , Zhang Zhengjian , Basham Stephen , Ho Jaclyn , Johnson Stephanie , Klammer Aaron , Lin Kevin , Darzacq Xavier , Betzig Eric , Berman Russell
Published: January 2024

Single-molecule localization microscopy (SMLM) techniques, such as single-molecule tracking (SMT), enable in situ measurements in cells from which data-rich metrics can be extracted. SMT has been successfully applied to a variety of biological questions and model systems, aiming to unravel the spatiotemporal regulation of molecular mechanisms that govern protein function, downstream pathway effects, and cellular function. While powerful, SMLM often suffers from low throughput and illumination inhomogeneity, along with microscope and user-induced technical biases. Due to technical limitations in scaling SMLM techniques, a tradeoff between spatiotemporal resolution and throughput has been made historically, restricting broad application of these technologies. Here we address these limitations using Oblique Line Scan (OLS), a robust single-objective light-sheet based illumination and detection modality that achieves nanoscale spatial resolution and sub-millisecond temporal resolution across a 250 x 190 µm field of view. We demonstrate OLS-enabled SMT on Halo-Tagged proteins in living cells capturing protein motion up to 14 µm2 /s. By exploiting the adaptability of the acquisition frame rate and the improved rejection of out of focus light, we extend the utility of OLS beyond cellular compartments with in-solution SMT (isSMT) for single-molecule measurement of ligand-protein interactions and disruption of protein-protein interactions (PPI). We illustrate the versatility of OLS by showcasing two-color SMT, STORM, and single molecule fluorescence recovery after photobleaching (FRAP). OLS expands the range of SMLM applications and paves the way for robust, high-throughput single-molecule investigations of protein dynamics required for drug screening and systems biology studies, both in cells and in solution.
Biomechanical evaluation of the effect of a stem cell enhancer on bone implant connection of titanium implants
Authors: Yilmaz-Bozoglan M. , Bozoglan A. , Sunar O. , Polat O. , Tekin B.
Published: January 2024

Background
This study aimed to conduct a biomechanical investigation of the effects of stem cell enhancer (SCE) application on osseointegration of titanium implants in rat tibias.
Methods
After surgical implantation of titanium implants in the metaphyseal part of the tibiae of rats, the rats were randomly divided into three equal groups (n = 10): control group, SCE Dosage group 1 (SCE1), and SCE Dosage group 2 (SCE2). Each group consisted of 10 rats. The rats in the SCE1 and SCE2 groups were administered 6 mg and 12 mg SCE (Stemregen®), respectively, every day during the four-week of experimental period after surgery. Implants and surrounding bone tissues were collected for biomechanical bone-implant connection analysis at the end of the experimental procedures. One-way ANOVA was used for statistical analysis.
Results
There was no significant difference in the biomechanical osseointegration values of the groups; however, the osseointegration of the SCE group was better than that of the control group.
Conclusions
Stem cell enhancers have the potential to improve the biomechanical bone-implant interface.
Ground deformation in and around Jigokudani valley, Tateyama volcano, Japan, during the period of 2021-2022 revealed from combined data of leveling surveys and GPS observations
Authors: Hotta Kohei
Published: January 2024

Ground deformation in and around Jigokudani valley during the period from September 2021 through September 2022 detected from leveling surveys and GPS observations was modeled to interpret what occurred beneath the Jigokudani valley accompanied by volcanic activities. Most leveling benchmarks showed uplift of up to 0.9 cm during the one-year period. Some benchmarks located west part of Jigokudani valley showed subsidence. Two GPS stations in the valley also showed uplift up to 1.4 cm. These two GPS stations showed horizontal displacements up to 1.6 cm. The GPS station locates out of fumarolic areas of the valley showed very small displacement. A dislocation source was applied to the deformation. Assuming a Poisson’s ratio of 0.45, the optimal parameters were searched using Adam. A crack with a length of 348 m, a width of 1.4 m and a dip of 86.7° is located at a depth of 6.8 m near Koya jigoku and the new fumarolic area, which has recently become highly activated. The strike of the crack is N239°E. The opening of the crack of 36.2 cm yields a volume increase of 173 m3. The obtained crack is considered to correspond to the shallow aquifer, and the aquifer pushed out by hot volcanic gas and generated water vapor. Further investigation, such as seismic prospecting, is needed to confirm the result and interpretation of the present study. Although overall deformation can be broadly explained by opening of the crack, there is some differences between observation and calculation probably because actual shape of the crack is more complex. In addition, it is necessary to construct a unified model, combining not only geodetic data but also other data such as seismic prospecting as raised above.
Heterogeneous shell growth of the neustonic goose barnacle Lepas anserifera:Its potential application for tracking floating materials
Authors: Watanabe Hiromi Kayama , Nagai Yukiko , Sakai Saburo , Kobayashi Genki , Yamamori Luna , Tada Noriko , Kuwatani Tatsu , Nishikawa Haruka , Horigome Takuto , Uehara Haruka , Yusa Yoichi
Published: January 2024

Floating materials of both natural and anthropogenic origin can affect marine ecosystems and human economic activities. Although the tracking and forecasting of floating materials are important, these processes are difficult to trace back after the events of origins, such as tsunamis and underwater volcanic eruptions. The goose barnacle Lepas anserifera, a rapid colonizer in pelagic environments, is a potential “natural logger” of floating materials. In this study, we performed temperature-controlled culture experiments and growth line identification in the laboratory to quantify the growth increments of individual shells consisting of the capitulum of L. anserifera and to examine the effects of the temperature on their growth. Following calcein staining, the growth line of L. anserifera was visualized under a fluorescent microscope, and gross (capitular length and width) and individual (scutum and tergum) shell growth were compared. Shells grew in twice as much in the CL direction than in the CW direction owing to the larger growth increases in the scutum than in the tergum. Growth increments were unaffected by temperatures from 20°C to 30°C, although growth appeared somewhat limited after August. The stable oxygen isotope composition (δ18O) of the shells represented the water temperature as previously known, and the present results showed that the scutum had heavier δ18O than the tergum in most cases. Further understanding for the biomineralization process of barnacles is required for the precise application of environmental proxies in barnacle shells.
Translation and validation to the Arabic language of the Climate Change Anxiety Scale (CCAS)
Authors: Fekih-Romdhane Feten , Malaeb Diana , Yakın Ecem , Sakr Fouad , Dabbous Mariam , Khatib Sami El , Obeid Sahar , Hallit Souheil
Published: January 2024

Background
The Arab world is one of the global regions the most directly concerned by, and suffering from climate change’s adverse consequences. As such, there appears to be a strong need for an understanding of how Arab people may emotionally respond to climate change. Providing valid and reliable measures of climate change anxiety (CCA) can help gain a clear overview of the situation in Arab countries, and allow to intervene timely and effectively to mitigate any adverse effects on Arab people’s mental health. To this end, the present study sought to validate the Arabic language version of the Climate Change Anxiety Scale (CCAS) in a sample of native Arabic-speaking adults from the general population of Lebanon.
Methods
This study adopted a cross-sectional approach and enrolled 763 adults between July and September 2023.
Results
A confirmatory analysis of the one-factor model showed poor fit indices as follows: CFI = .90, GFI = .83, SRMR = .048 and RMSEA .131 [90% CI .123, .138). The two-factor model showed a satisfactory fit with a high CFI of and a GFI of 0.91 and a SRMR of 0.04 and RMSEA of 0.05 [90% CI 0.04, 0.06]. Both McDonald’s omega and Cronbach alpha values were high for the overall CCAS score (α = .96 and ω = .96) in the whole sample. Configural, metric and scalar invariance across gender was demonstrated. No significant difference was found between males and females in terms of total CCAS scores (24.53 ± 10.59 vs 26.03 ± 11.17, t(761) = -1.82, p = .069). Higher CCA, functional impairment and cognitive impairment scores were significantly associated with higher depression, anxiety and stress.
Conclusion
The reliability and validity of the CCAS in its Arabic version were proven. The availability of this self-report measure could offer a chance to assess CCA among Adults speaking Arabic, and to spread its future use for screening and research purposes.
Reliability of industrial-scale telescopes in the event of seismic failures
Authors: Cho Anthony D. , Jiménez Dora , Guevara Esnil
Published: January 2024

Natural disasters have the potential to pose a significant threat to property, critical infrastructure, human health and safety, and some others. One of the most relevant natural disasters is earthquakes, which are high on the list of natural phenomena that most affect infrastructures and, at the same time, are the most unpredictable. This study uses the probabilistic seismic risk analysis method to estimate the condition of an industrial-scale telescope after the effect of an earthquake. The approach considers a seismic source model and ground motion prediction equations to evaluate the intensity measure of each telescope as a function of its location. Our simulation uses reliability via Monte Carlo to discover the probability of failure of each telescope taking into consideration the fragility curves described by its nature structure. Our method incorporates terrain characteristics and component robustness into the analysis of telescope performance at an affordable computational cost. We applied our method to the observatories that use industrial-scale telescopes established in Chile, and we showed that reliability is highly dependent on the robustness/fragility of the infrastructure.
MSC Classification: 62P12 , 62P30 , 90B25
Exploring the Mechanism of Dendrobine in Treating Non-Alcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Validation
Authors: Li Feng , Wu Jialin , Zhu Ye , Zhang Xiaoyan , Wang Miao , Zhou Shigao
Published: January 2024

This research delves into the therapeutic mechanisms of Dendrobine, the primary bioactive compound in Dendrobium nobile, for Non-Alcoholic Fatty Liver Disease (NAFLD) management. Integrating network pharmacology with experimental validation, the study evaluates the clinical effectiveness and safety of Dendrobium nobile in NAFLD treatment through an exploratory clinical trial. The approach identifies Dendrobine's potential targets and associated genes, constructing an interactive gene network. Validation processes include functional genomics, pathway enrichment analysis, molecular docking, cellular assays, and qPCR. Results demonstrate Dendrobium nobile's efficacy in enhancing liver function among NAFLD patients. Network pharmacology findings indicate Dendrobine’s influence on key targets like PPARG, IL6, TNF, IL1B, and AKT1, with molecular docking confirming interactions across these targets, excluding NFKB1. Dendrobine significantly reduced ALT and AST levels in PA-treated HepG2 cells, suggesting hepatoprotective properties, and ameliorated oxidative stress by lowering MDA levels and increasing SOD levels. The findings suggest Dendrobine's role in modulating inflammatory and immune responses, potentially through the downregulation of inflammatory mediators like TNF, IL6, and IL1B, and influencing lipid metabolism via AKT1 and STAT3 inhibition, thereby mitigating liver damage in NAFLD.
Acute myeloid leukemia patients with high-risk karyotypes benefit from decitabine in combination with modified CAG
Authors: Liu Wen-Jie , Sun Qian , Zhu Yu , Zhao Xiao-Li , Li Jian-Yong , Qian Si-Xuan , Hong Ming
Published: January 2024

This study aims to investigate the cytogenetic and molecular characteristics of patients with Acute Myeloid Leukemia (AML) and determine which patients would benefit most from a low-intensity regimen of decitabine in combination with modified CAG (D-CAG) or intensive chemotherapy. We retrospectively analyzed cytogenetic and molecular data from 331 newly diagnosed AML patients and investigated the relationship between genetic characteristics, risk status, treatments and clinical outcomes. The median followed-up was 45 months (2-120 months). Overall, a single cycle of IA induction resulted in a CR rate of 79.3%, which was superior to the 66.4% observed in the cohort treated with D-CAG (P < .05). However, there was no significant difference in ORR between the two arms. The median OS was reduced in the D-CAG cohort compared to the IA cohort (P < .05). Favorable-risk groups and patients who undergo allo-HSCT treated with IA had longer OS than those in the D-CAG groups (P < .05). While the median OS of the intermediate- and high-risk groups who were not recipients of allo-HSCT was comparable between two regimen. Within the IA group, patients with TET2, NRAS, and biallelic CEBPA gene mutations achieved better OS than those in the D-CAG group (P < .05). While older patients with complex and monosomal karyotypes were tend to have longer median OS compared to younger patients (P < .05). In conclusion, it is crucial to select AML chemotherapy regimens based on karyotypes and genetic characteristics. D-CAG may be a better choice for AML patients with high-risk karyotypes.
Healthcare Providers' Perspectives on Sustaining Respectful Maternity Care Appreciated by Mothers, in Five Hospitals of Rwanda
Authors: Muhayimana Alice , Kearns Irene
Published: January 2024

Background: Childbirth demands respect, as emphasized by the World Health Organization in 2018 and the focus towards the need for positive, dignified delivery experiences, has become an integral aspect of Respectful Maternity Care (RMC). It is a known fact that RMC is pivotal for favorable birth outcomes and reduce mistreatment during childbirth. Absence of RMC violates women and newborns' rights, and the study aims to explore Health Care Providers' perspectives on sustaining RMC actions previously reported by mothers.
Methodology: This study was conducted in five hospitals in the Eastern province of Rwanda, involving 5 Focus Group Discussions (FGDs) with midwives and nurses. For interviews, we purposively selected 5-unit managers and 5 physicians. Additionally, 40 midwives and nurses were recruited for the FGDs. The research utilized the Dream phase of Appreciative Inquiry (AI) for interviews and Focus Groups. Data collection aimed to gain insights into Healthcare Providers' perceptions of how RMC is provided and how to establish and to sustain RMC in Rwandan health facilities. Nvivo 12 was employed for organizing codes and creating a codebook, and thematic analysis was applied.
Results: 4 themes emerged and their sub-themes.1) Women centered care withCompassionate care, Privacy and confidentiality maintenance, Information provision and liberty in decision making, Effective communication, Family involvement, Cleanness Equality care. 2)Professionalism compliance with Motivated staff, Teamwork, Continuous development, Quality work provision, Community trust. 3) RMC encounters 4) RMC sustenance
Conclusion and recommendations: The continuous pursuit of high RMC standards in Rwanda involves improving childbirth experiences through utilizing existing resources, ongoing improvement, and sustaining achievements. Key recommended actions in this study for sustaining RMC encompass promoting women-centered care, enhancing healthcare provider attitudes, ensuring professionalism, building community trust, maintaining conducive health facility environments, and involving leadership
Modeling Lassa fever in Nigeria with perception of risk
Authors: Agusto Folashade B.
Published: January 2024

Lassa fever is an acute viral hemorrhagic disease caused by Lassa virus. It is transmitted to humans through direct contactwith infected mastomys natalensis rodents, or through food or household items contaminated with urine or feces of infectedrodents. Nigeria is an endemic country for Lassa fever, the current overall risk at the national level is considered high due toseveral factors including lack of awareness and education about the disease. In this study, a mathematical model of Lassa fevertransmission with perception of risks was developed. The model was parameterized using Lassa fever data from 2017-2022obtained from Nigerian Centers for Disease Prevention and Control. Results of the global sensitivity analysis shows thesignificant impact of rodent-to-rodent, rodent-to-human and human-to-human transmission probabilities, as well as perceptionof risks terms on the response functions. Other influential parameters are the rodent growth and death rates as well as humanrecovery and disease progression rates. Humans’ natural death and disease induced death rates including perception of riskdecay term all have impact on the response functions. The distribution profile of the reproduction number values is within theinterval [0.7801,3.0049] for years 2017–2022. The simulation results show that increase in transmission probabilities increasethe disease burden in the community while increase in perception of risks of the disease decreases the disease burden.
Exploring the Reasons for Defaulting from Childhood Immunization: A Qualitative Study in District Swat Pakistan
Authors: Ullah Kifayat , Saleem Javeria , Zakar Rubeena , Ishaq Muhammad , Khattak Farhad Ali , Majeed Fatima , Sadiqa Hafiza Aisha , Fischer Florian
Published: January 2024

Background:Childhood vaccination is widely recognized as the most effective means to prevent various diseases. However, a considerable amount of children still miss out on their vaccination schedules. Therefore, this study explores the reasons for defaulting from the expanded program on immunization in district Swat, Pakistan.
Methods: A qualitative phenomenological approach was used. Data collection took place from March to September 2022. Thirty-six in-depth interviews were conducted with participants who had defaulter children. The collected qualitative data were analysed thematically to identify key patterns and themes related to the reasons for defaulting from childhood vaccination schedules.
Results: Six themes emerged, i.e., illness of the defaulter child at the scheduled time, perceived side effects of the vaccination, factors related to caregivers, myths and misconceptions, vaccinators attitudes and crowed vaccination centres, as well as poor immunization service arrangements. Four subthemes arose related to caregivers, such as lack of clear understanding about completion of vaccination, least priority for child’s vaccination, cultural restriction on mothers, and the loss of vaccination card.
Conclusion:According to the study’s findings, most caregivers had their perceptions about not completing the children’s vaccination schedule. The vaccination completion rate may be increased if the concerns of the caregivers are appropriately addressed.
Assessing and comparing Knowledge, Attitude, and Practices related to Water, Sanitation and Hygiene Among Government and Non-government School students in Gujarat: A Mixed-Method Study
Authors: Patel Monika , Gupta Eshwar Kumar , M Yogesh
Published: January 2024

Background: Water, sanitation, and hygiene (WASH) practices are vital for health, especially among school students who can propagate messages. Comparing WASH knowledge, attitudes and practices between government and non-government schools can guide tailored interventions. This mixed methods study aimed to assess and compare WASH-related knowledge, attitudes, and practices among adolescents in government versus non-government schools in Gujarat, India.
Materials and Methods: A cross-sectional survey was conducted among 566 students from 17 government and 17 non-government schools. Interviews using a standardized questionnaire provided quantitative data on WASH-related knowledge, attitudes, and practices. Qualitative data was gathered through focus group discussions exploring influences on student WASH behaviors. Analyses included descriptive statistics, group comparisons, multivariate regression, and thematic analysis. A-value of P <0.05 was considered significant.
Results: In total, 566 students participated, with 257 (45%) from government and 309 (55%) from non-government schools. Non-government students showed significantly better knowledge of handwashing (AOR 1.9, 95% CI 1.3-2.7), fecal-oral transmission (AOR 1.8, 95% CI 1.3-2.5), open defecation (AOR 1.7, 95% CI 1.2-2.4), and menstrual hygiene (AOR 3.2, 95% CI 1.1-9.2). More non-government students had positive attitudes about safe drinking water (AOR 4.1, 95% CI 1.8-9.6), conserving water (AOR 2.0, 95% CI 1.4-2.9), cleanliness (AOR 1.8, 95% CI 1.1-2.9), investing in hygiene (AOR 5.3, 95% CI 3.1-9.2), and menstrual management (AOR 2.1, 95% CI 1.2-3.6). In practices, non-government students showed higher use of soap (AOR 1.9, 95% CI 1.3-2.8), better menstrual hygiene (AOR 5.9, 95% CI 3.2-10.9), and more sanitary defecation (AOR 2.7, 95% CI 1.8-4.0). Superior WASH outcomes were associated with older age (AOR 1.8, 95% CI 1.1-3.0), urban locality (AOR 2.3, 95% CI 1.5-3.5), higher parental education (AOR 2.1, 95% CI 1.3-3.4), and affluence (AOR 3.1, 95% CI 1.8-5.2). Qualitative data highlighted knowledge gaps, inadequate facilities, detrimental cultural beliefs, poverty, and the need for government support.
Conclusions: Disparities exist in WASH behaviors between school types, suggesting the need for tailored interventions addressing specific gaps. Schools play a critical role in cultivating proper hygiene through infrastructure provision and targeted education. Government schools may require extra support to overcome challenges related to WASH access and quality.
Unraveling the Ground Subsidence Disaster Caused by Rock Salt Mining in Maceió (Northeast Brazil) from 2020 until Rupture Using Sentinel-1 Data
Authors: Mantovani Jose , Enner
Published: January 2024

Maceió, the capital of Alagoas, grapples with subsidence, a geophysical challenge rooted in coastal influences, anthropogenic activities, and geological factors. The consequences, ranging from structural damage to increased flood vulnerability, impact communities, notably in neighborhoods like Bebedouro and Farol. Addressing subsidence demands a comprehensive approach, integrating geotechnical engineering, urban planning, and environmental management. The dataset reveals a nuanced relationship between subsidence and urban parameters. High-density urban areas bear a disproportionate burden, emphasizing the intricate link between urbanization and ground movement. The influence of topography challenges assumptions, indicating that areas with steeper slopes exhibit lower rates of ground movement. Temporal analysis underscores the dynamic nature of subsidence, influencing the spatial distribution of occupied areas. Recognizing subsidence as an evolving phenomenon allows for adaptive strategies in dynamic urban planning. This aligns with existing literature, emphasizing the need for adaptive planning, resilient infrastructure, and targeted interventions. In conclusion, Maceió's subsidence challenges necessitate a geotechnically informed, nuanced approach, considering local variations, community engagement, and temporal dynamics. Collaborative efforts between stakeholders are crucial for sustainable solutions and urban resilience in the face of subsidence-induced complexities.
FATP2 activates PI3K/Akt/mTOR pathway by inhibiting ATF3 and promotes the occurrence and development of bladder cancer
Authors: Jiang Ming , Chen Ru , Hu Bing , Xiong Situ , Li Sheng , FU Bin , Liu Xiaoqiang
Published: January 2024

Bladder cancer (BLCA) is ranked among the main causes of mortality in male cancer patients, and research into targeted therapies guided by its genomics and molecular biology has been a prominent focus in BLCA studies. Fatty acid transporter protein 2 (FATP2/SLC27A2), a member of the FATPs/SLC27As family,is a key contributor to the progression of cancers such as hepatocellular carcinomas and melanomas.However,its role in BLCA remains poorly understand. This study delved into the function of FATP2 in BLCA through a succession of experiments in vivo and in vitro, employing techniques as quantitative real-time polymerase chain reaction (qRT-PCR), RNA sequencing, transwell assays, immunofluorescence,western blot,and others to dissect its mechanistic actions. The findings revealed that an oncogenic function is executed by FATP2 in bladder cancer, significantly impacting the proliferation and migration capabilities, thereby affecting the prognosis of BLCA patients. Furthermore, A suppression that relies on both time and concentration of BLCA proliferation and migration, trigger of apoptosis, and blockage of the cell cycle at the G2/M phase were observed when the inhibitor of FATP2, Lipofermata, was applied. It was unveiled through subsequent investigations that ATF3 expression is indirectly promoted by Lipofermata through the inhibition of FATP2, ultimately inhibiting the signal transduction of the PI3K/Akt/mTOR pathway. This effect was also responsible for the inhibitory impact on BLCA proliferation. Therefore, FATP2 emerges as an auspicious and emerging molecular target with potential applications in precision therapy in BLCA.
Serum Neurofilament Light Chain and Inflammatory Cytokines as Biomarkers for Early Detection of Alzheimer's Disease
Authors: Jing Xinyang , Wang Lan , Song Mei , Geng Hao , Li Wei , Huo Yaxin , Huang Anqi , Wang Xueyi , An Cuixia
Published: January 2024

Objective: To investigate the association between serum neurofilament light chain (NfL) levels, inflammatory cytokines, and cognitive function to assess their utility in the early detection of Alzheimer's disease (AD).
Methods: We conducted a cross-sectional study involving 157 community-dwelling individuals aged 55 years and above, categorized into healthy controls, mild cognitive impairment (MCI), and probable AD. Serum levels of NfL, inflammatory cytokines, and AD pathology markers were measured using enzyme-linked immunosorbent assay (ELISA). Correlations between these biomarkers and cognitive function were analyzed, for the potential of serum NfL in recognizing MCI.
Results: Serum NfL levels were significantly elevated in MCI and probable AD groups compared to healthy controls. Positive correlations were found between serum NfL and inflammatory cytokines IL-1β, IL-6, and Aβ40. Combining serum NfL with p-tau217 and the Boston Naming Test significantly enhanced the predictive accuracy for MCI. However, combining serum NfL with inflammatory markers did not improve MCI prediction accuracy.
Conclusions: Elevated serum NfL is associated with cognitive impairment and inflammatory markers, suggesting its potential as a peripheral blood biomarker for early AD detection. The combination of serum NfL with p-tau217 and cognitive tests could offer a more accurate prediction of MCI, providing new insights for AD treatment strategies.
Xanthine oxidase modulates Glutamic Acid Decarboxylase 65 isoform (GAD65) protein expression in rat pancreatic islets
Authors: RAZDAN KONIKA , RAINA VARSHIESH
Published: January 2024

Background: It is widely presumed that aberrant expression of GAD65 can sensitize beta cells to autoimmunity and moreover, several studies indicate Xanthine Oxidase (XO) plays significant role in Type-1 diabetes (T1D) pathology. The present study aimed to investigate whether XO modulates GAD65 protein expression in rat islets/pancreas in presence or absence of STZ.
Methods and results: Female Wistar rats were used for pancreatic islet isolation and T1D STZ model by injecting single dose of STZ (40 mg/kg body weight). GAD65 and XO protein expression was studied by immunoblot in islets/pancreas and STZ/T1D cytokines (such as IL-1 beta, TNF-α and IFN-γ)/XO siRNA/Allopurinol (XO inhibitor)/1400W (iNOS inhibitor) were used in treatment groups. Enzymatic assay was done to measure XO activity in islets/serum/pancreas and iNOS activity in culture supernatant. STZ led to a significant increase in GAD65 expression and XO activity in islets which was reduced in presence of Allopurinol and XO siRNA. In pancreas of T1D rat model, expression of GAD65 decreased and XO increased; XO activity decreased; whereas in sera XO activity increased. Treatment of islets with T1D cytokines revealed that cytokine cocktail declined GAD65 protein levels and XO activity and intervention with iNOS inhibitor reversed the effect. During ontogeny of pancreas GAD65 expression was more in the fetal/infantile pancreas compared to adult pancreas and Allopurinol challenged pregnant rats confirmed that GAD65 expression is dependent on XO activity. Conclusion: This study for the first time clearly demonstrates that XO is positive regulator of GAD65 expression in rat islets and STZ-T1D model.
Bushen Tongluo decoction attenuates epithelial-mesenchymal transition and extracellular matrix deposition in pulmonary fibrosis rats by inactivating Wnt3a/β-catenin signaling pathway
Authors: liang yanxia , su wenwen , li guangsen , wang wenwen , liu fenggu , zhao xiaoli , mu qingxiang , zhang jiaoqiang , zhao huiying , xing hongfei , fan maorong , yang bin
Published: January 2024

Context: Bushen Tongluo Decoction (BTD), a traditional Chinese herbal preparation that has shown efficacy in improving symptoms and enhancing the quality of life in IPF patients. However, the molecular mechanisms of BTD require further research.
Objective: This study explores the protective effect of BTD in pulmonary fibrosis rats and elucidate its underlying mechanism.
Materials & methods: Pulmonary fibrosis model was established using boromycin. Rats were divided into control, model, pirfenidone, high-dose BTD, low-dose BTD groups treating for 90 days. Laminin in serum, TGF-β1, IFN-γ, and IL-4 in BALF was measured using Elisa. Pathological changes were observed by HE and Masson staining. The expression of EMT markers (E-cadherin, cytokeratin 19, α-SMA, vimentin) and ECM markers (collagen I, collagen III) were assessed using immunohistochemistry. Levels of Wnt3a and β-catenin in lung tissue was measured by Western blotting.
Results: BTD reduced serum Laminin levels, reduced the levels of TGF-β1 and IL-4 in BALF, increased IFN-γ levels in BALF. BTD alleviated lung pathological injury, decreased the lung expression of α-SMA, Vimentin, Collagen I, Collagen III, and increased the levels of E-cadherin, Cytokeratin 19 in rats with pulmonary fibrosis, indicating its ability to alleviate EMT in alveolar epithelial cells. Mechanistically, BTD significantly inactivates the Wnt3a/β-catenin signaling pathway in IPF.
Discussion & conclusion: BTD alleviated lung fibrosis in rats with pulmonary fibrosis, alleviating lung injury, reducing ECM deposition, attenuating the EMT process, through inactiving the activation of the Wnt3a/β-catenin signaling pathway.
Incidence Rate of Occult Lymph Node Metastasis in Clinical T 1-2 N 0 M 0 Small Cell Lung Cancer Patients and Radiomic Prediction Based on Contrast-enhanced CT Imaging: A Multicentre Study
Authors: Jiang Xu , Luo Chao , Peng Xin , Zhang Jing , Yang Lin , Liu Li-Zhi , Cui Yan-Fen , Liu Meng-Wen , Miao Lei , Jiang Jiu-Ming , Ren Jia-Liang , Yang Xiao-Tang , Li Meng , Zhang Li
Published: January 2024

Background
This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 − 2N0M0 (cT1 − 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data.
Methods
By conducting a retrospective analysis involving 242 eligible patients from 4 centres, we determined the incidence of OLM in cT1 − 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV).
Results
The initial investigation revealed a 33.9% OLM positivity rate in cT1 − 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for T1 − 2N0M0 SCLC patients.
Conclusions
The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 − 2N0M0 SCLC.
Transcultural adaptation and validation of IMPACT-III and IMPACT-III-P in Spanish families: A multicenter study from SEGHNP
Authors: Rodríguez-Belvís Marta Velasco , Palomino Laura , Muncunill Gemma Pujol , Martin-Masot Rafael , Benítez Enrique Medina , Fernández-Lorenzo Ana Estefanía , Moreno-Álvarez Ana , Arias Manuel Molina , Montes Inmaculada Hidalgo , Torres Josefa Barrio , Navas-López Víctor Manuel , de Carpi Javier Martín
Published: January 2024

Purpose: IMPACT-III and IMPACT-III-P are health-related quality of life (HRQoL) questionnaires for patients with pediatric inflammatory bowel disease (p-IBD) and their parents/caregivers. We aimed to perform a transcultural adaptation and validation for the Spanish context.
Methods: Translation, back-translation, and evaluation of the questionnaires was performed by an expert committee and 12 p-IBD families. We recruited p-IBD patients aged 10-17 and their parents/caregivers. Utility, content, and face validity were considered. Validation was performed with Cronbach's alpha coefficient and varimax rotation. We confirmed the adequacy of the factor analysis using Kaiser-Meyer-Olkin (KMO) and Bartlett’s sphericity tests. A confirmatory factor analysis was performed using the following goodness indexes: chi-square, Normed Fit Index (NFI), Root Mean Square Error of Approximation index (RMSEA), Standardized Root Mean Square Residual (SRMR), and Comparative Fit Index (CFI). The correlation coefficient between IMPACT-III and IMPACT-III-P was analyzed.
Results: We included 370 patients and 356 parents/caregivers (37 hospitals). Both questionnaires had good content and face validity and were considered user-friendly. The KMO measure (0.8998 and 0.9228, respectively) and Bartlett’s sphericity test (p-value <0.001 for both) confirmed the adequacy of the factor analysis. The 4-factor model, complying with Kaiser’s criterion, explained 89.19% and 88.87% of the variance. Cronbach's alpha (0.9123 and 0.9383) indicated excellent internal consistency. The CFA showed an adequate fit (NFI 0.941 and 0.918, RMSEA 0.048 and 0.053, SRMR 0.037 and 0.044, CFI 0.879 and 0.913). The correlation coefficient was excellent (0.92).
Conclusions: The SEGHNP versions of IMPACT-III and IMPACT-III-P are valid and reliable instruments for Spanish p-IBD families.
VoLTE Call Blocking Estimation in Cellular LTE Network
Authors: Dehury Mohan Kumar , Pati Hemanta Kumar
Published: January 2024

In recent years, Voice over LTE (VoLTE) has emerged as a significant technological solution for delivering voice services in wireless cellular networks. However, it’s often observed that call blocking occurs in Long Term Evolution (LTE) network when initiating new calls and during handoff procedures from one cell to another. New call requests may be blocked due to configuration failures, and handoff call failures can result from reconfiguration issues. These failures typically arise from the unavailability of radio resources. The availability of resources, specifically within LTE cells providing VoLTE service, vary depending on the combination of voice codecs and Modulation and Coding Scheme (MCS) used. This variability significantly impacts the call blocking performance of the LTE network, and requires further investigation. In this paper, we propose an analytical model based on Physical Resource Block (PRB)s utilizing Markov chain approach to reflect LTE scenarios delivering VoLTE service. Using this model, we estimate the VoLTE call blocking probability in the LTE network while considering different combinations of voice codecs and MCSs, as recommended by Third Generation Partnership Project (3GPP).
Enhancing Object Segmentation Model with GAN-based Augmentation using Oil Palm as a Reference
Authors: Kwong Qi Bin , Kon Yee Thung , Rusik Wan Rusydiah W , Shabudin Mohd Nor Azizi , Kulaveerasingam Harikrishna , Rahman Shahirah Shazana A , Appleton David Ross
Published: January 2024

In digital agriculture, a central challenge in automating drone applications in the plantation sector, including oil palm, is the development of a detection model that can adapt across diverse environments. This study addresses the feasibility of using GAN augmentation methods to improve palm detection models. For this purpose, drone images of young palms (< 5 year-old) from eight different estates were collected, annotated, and used to build a baseline detection model based on DETR. StyleGAN2 was trained on the extracted palms and then used to generate a series of synthetic palms, which were then inserted into tiles representing different environments. CycleGAN networks were trained for bidirectional translation between synthetic and real tiles, subsequently utilized to augment the authenticity of synthetic tiles. Both synthetic and real tiles were used to train the GAN-based detection model. The baseline model achieved precision and recall values of 95.8% and 97.2%, whereas the GAN-based model achieved precision and recall values of 98.5% and 98.6%. In the challenge dataset 1 consisting older palms (> 5 year-old), both models also achieved similar accuracies, with baseline model achieving precision and recall of 93.1% and 99.4%, and GAN-based model achieving 95.7% and 99.4%. As for the challenge dataset 2 consisting of storm affected palms, the baseline model achieved precision of 100% but recall was only 13%, whereas GAN-based model achieved a high precision and recall values of 98.7% and 95.3%. This result demonstrates that images generated by GANs have the potential to enhance the accuracies of palm detection models.
Development of wound healing scaffold using ZnO and TiO2 nanoparticles
Authors: Samadian Fatemeh , Beygi-Khosrowshahi Younes
Published: January 2024

The goal of this experiment is to produce a nanocomposite porous scaffold, using an electrospinning method that has biological properties to use as a skin tissue engineering (TE) and wound dressing. Polyhydroxyethyle methacrylate (PHEMA), polycaprolactone (PCL), Titanium oxide (TiO2) nanoparticles, and zinc oxide (ZnO) nanoparticles, used to fabricate this scaffold. After the polymers were synthesized, both polymers were dissolved in chloroform, and nanoparticles were added. The diameter of the fibers obtained depends on the amount of addition of each nanoparticle, the injection rate of the device and the voltage, and the distance between the collector and the needle. Scanning electron microscopy (SEM) images showed the morphology of the scaffold and the cells can adhere well to nanofibers. The mechanical property test showed appropriate mechanical properties for this polymeric scaffold. X-ray diffraction pattern (XRD) and Fourier transform infrared spectroscopy (FTIR) results confirm the successful loading of nanoparticles into the polymer scaffold. Other biological features are characterized with, in vivo assay and MTT and antibacterial assay. The results show that this scaffold is suitable to use as a skin tissue scaffold and wound dress.
Results from phase one of a hybrid effectiveness-implementation study to assess the feasibility, acceptability and effectiveness of implementing seasonal malaria chemoprevention in Nampula province, Mozambique
Authors: Baker Kevin , Tarquino Ivan Alejandro Pulido , Aide Pedro , Bonnington Craig , Rassi Christian , Richardson Sol , Nnaji Chuks , Roca-Feltrer Arantxa , Rodrigues Maria , Sitoe Mercia , Enosse Sonia , McGugan Caitlin , Saute Francisco , Matambisso Gloria , Candrinho Baltazar
Published: January 2024

Introduction Seasonal malaria chemoprevention (SMC) is a highly effective intervention for malaria prevention in high burden areas with seasonal transmission, historically implemented in the Sahel. Mozambique contributes to 4% of global malaria cases, malaria being one of four major causes of mortality nationally. The mid-term review of the Malaria Strategic Plan 2017–2022 recommended SMC in Mozambique. Malaria Consortium, in partnership with the National Malaria Control Program, conducted a two-year phased SMC study in Nampula province using sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), or SPAQ, in children under five. Phase one investigated acceptability, feasibility, and protective effect of SMC; while phase two, researched the effectiveness of SMC, chemoprevention efficacy and changes in resistance markers prevalence. The following references phase one results.Methods A pragmatic type II hybrid effectiveness-implementation study design was adopted, using mixed methods. The study was conducted in three districts, utilising: (1) non-randomised controlled trial; (2) drug resistance molecular marker study; (3) coverage and quality assessment; and (4) acceptability and feasibility assessment with stakeholders.Results Children who received SMC had 86% (hazard ratio 0.14, 95% CI: 0.09–0.24) lower hazards of developing clinical malaria during the peak transmission season compared with children in the comparison district. Prevalence of SP molecular markers associated with resistance was high at baseline (K540E 66.1%). However, a non-statistically significant trend of increasing prevalence was observed. SMC achieved high coverage of eligible children over four cycles (87.7%, 95% CI: 83.9%-90.8%). Qualitative results indicate SMC was positively accepted by the targeted community, with few negative opinions reported.Conclusions Results suggest that SMC was effective at preventing clinical malaria, did not significantly impact resistance profile, and was feasible and acceptable in the context. Phase two will assess SMC impact in reducing malaria incidence and if chemoprevention efficacy of SPAQ is impacted by drug resistance and drug concentrations.
TET2 and clonal hematopoiesis-related gene variants in patients with acquired pure red cell aplasia
Authors: Ishida Fumihiro , Kawakami Toru , Kawakami Fumihiro , Matsuzawa Shuji , Yamane Taku , Mizuno Yuga , Asakura Ami , Higano Daigo , Miyairi Shotaro , Sakai Kaoko , NIshina Sayaka , Sakai Hitoshi , Kubota Yasushi , Higuchi Yumiko , Nakazawa Hideyuki
Published: January 2024

Dysregulation of T cell-mediated immunity is considered a major pathophysiological mechanism of acquired pure red cell aplasia (PRCA), such as idiopathic PRCA, large granular lymphocytic leukemia-associated PRCA, and thymoma-associated PRCA. Although STAT3 mutations are frequently detected in PRCA patients, other mutational profiles and their involvement in the clinical characteristics are yet to be clarified. Whole-exome sequencing and targeted sequencing were performed using a custom-designed panel for PRCA (n = 53). The frequently mutated genes were NEB (40%), STAT3 (36%), PCLO (30%), TET2 (23%), and KMT2D (15%). Four of the 12 patients with mutations in TET2 had germline TET2 variants. Patients positive for TET2 variants had significantly more variants of lymphoid clonal hematopoiesis-related genes than those without TET2 variants (11/12 vs. 23/41, P = 0.038). Patients with TET2 variants relapsed after immunosuppressive therapy more frequently than those without TET2 variant (55% [6/11] vs. 11% [4/35], P = 0.0065). These data suggest that variants of clonal hematopoiesis-related genes, including TET2, in addition to STAT3, play important roles in the pathophysiology of PRCA.
Evolution At Spike Position 519 in SARS-CoV-2 Facilitated Adaptation to Humans
Authors: Weger-Lucarelli James , Cereghino Chelsea , Michalak Kasia , DiGiuseppe Stephen , Guerra Juan , Yu Delaney , Faraji Ariana , Sharp Amanda , Brown Anne , Kang Lin , Michalak Pawel
Published: January 2024

As the COVID-19 pandemic enters its fourth year, the pursuit of identifying a progenitor virus to SARS-CoV-2 and understanding the mechanism of its emergence persists, albeit against the backdrop of intensified efforts to monitor the ongoing evolution of the virus and the influx of new mutations. Surprisingly, few residues hypothesized to be essential for SARS-CoV-2 emergence and adaptation to humans have been validated experimentally, despite the importance that these mutations could contribute to the development of effective antivirals. To remedy this, we searched for genomic regions in the SARS-CoV-2 genome that show evidence of past selection around residues unique to SARS-CoV-2 compared with closely related coronaviruses. In doing so, we identified a residue at position 519 in Spike within the receptor binding domain that holds a static histidine in human-derived SARS-CoV-2 sequences but an asparagine in SARS-related coronaviruses from bats and pangolins. In experimental validation, the SARS-CoV-2 Spike protein mutant carrying the putatively ancestral H519N substitution showed reduced replication in human lung cells, suggesting that the histidine residue contributes to viral fitness in the human host. Structural analyses revealed a potential role of Spike residue 519 in mediating conformational transitions necessary for Spike to adopt an up configuration prior to binding with ACE2. Pseudotyped viruses bearing the putatively ancestral N519 also demonstrated significantly reduced infectivity in cells expressing the human ACE2 receptor compared to H519. Biochemical assays corroborated that N519 binds human ACE2 with lower affinity than H519. Collectively, these findings suggest that the evolutionary transition at position 519 of the Spike protein played a critical role in SARS-CoV-2 emergence and adaptation to the human host. Additionally, this residue presents as a potential drug target for designing small molecule inhibitors tailored to this site.