bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Community Development and Empowerment Programs in Samarinda City: An Analysis of Online News Articles
Authors: Fahlevy Muhammad Reza , Qolbi Yahdi , Jumansyah Jumansyah , Ahimsa Hayamaputra Marcello
Published: July 2024

This paper seeks to explore how online news media frame the achievement of the implementation of the community development and empowerment program (Pro Bebaya) in Samarinda City. This research investigates the success factors, obstacles, and challenges in implementing Pro Bebaya. This research aims to evaluate the implementation of the Pro Bebaya policy and assist the government, local parliament (DPRD), and the community in planning future policy programs. This research uses an inductive methodology to conduct content and qualitative narrative analysis of news stories published between January 2022 and February 2023. The dataset consists of articles from eleven leading online news sites in Indonesia. Qualitative content analysis shows that the news media Antaranews, Infosatu, Kaltimminutes, and Timeskaltim do much reporting on the achievement of the implementation of Pro Bebaya. Other success factors' findings include involvement and coordination with stakeholders, a control system, socialization by the government to the community, information sharing, tangible changes in infrastructure, and increasingly developed apparatus knowledge. Then, these factors led to the smooth implementation of program activities. Further but insignificant are the barriers and challenges, such as the lack of community involvement and knowledge in program implementation and budget constraints. Our findings support the argument that implementing government decisions or policies is based on actual action practices.
Do Macroeconomic Variables Affect Deposits in Shariah Banks?
Authors: Harini Ayunseh Retno , Kurniawan Mahrus , Putra Budi Jaya
Published: July 2024

Banks are intermediary institutions that collect funds from the public and channel them back in the form of credit and the funds collected are third party funds (TPF) which are the largest source of funds relied on by banks, including sharia banking. The challenge of sharia banking is to expand market share. Currently in Indonesia the banking market share is dominated by conventional banking. Increasing market share will increase savings in sharia banking and strengthen sharia banking as an intermediation institution. The research aims to identify the influence of macroeconomic variables on deposits in sharia banking. The research uses time-series data 2012: Q1 - 2022: Q1 and the ARDL method to estimate the short- and long-term influence of macroeconomic variables on TPF. The research results show that there are two variables that influence the short and long term, namely the GDP variable and the exchange rate. Meanwhile, inflation and interest rate variables only have an effect in the short term. The implications of the research show that increasing economic growth must be followed by increasing people's income and the stability of the rupiah exchange rate will increase people's deposits or savings in sharia banking.
Farmer Satisfaction with Financing Services at Sharia Microfinance Institutions Agribusiness (Sharia MFI-A)
Authors: Fitriana Widya
Published: July 2024

The total share of financing for the agricultural sector from financial institutions in Indonesia is still relatively low. It is because the agriculture sector is considered high-risk and not bankable. Even though the demand for financing from the agricultural sector is very high. Sharia MFI-A is a financing institution friendly to farmers because it has Sharia principles and shares risks. The loyalty of its customers determines the sustainability of this business. Service quality and customer expectation are affect customer satisfaction. This study aims to analyze service attributes considered necessary by customers and customer satisfaction to financing services at Sharia MFI-A. This research was conducted in West Sumatra, a province famous for its local principles of “Adat basandi sayarak, syarak basandi kitabullah”. The research was conducted on Sharia MFI-A namely in Agam Regency. The respondents were farmers who received financing in 2022. Five variables were observed: tangible, reliability, responsiveness, assurance, and empathy and measured using the Likert scale. Data analysis used Importance Performance Analysis (IPA) and Customer Satisfaction Index (CSI). The results showed that CSI’s score on Sharia MFI-A services is 88.28%, including the range of very satisfied criteria. Customers expressed very satisfaction with the performance of Sharia MFI-A services because the office is clean and comfortable, fast and friendly service, guaranteed customer confidentiality, and proft sharing transparency. This is by the principles of sharia services, namely fairness, and honesty in transactions ('adl wa tawazun), maslahah, and does not contain gharar and riba. Customer satisfaction with the services will affect farmers' loyalty to utilizing financing services from Sharia MFI-A in the future.
The Nexus between Financial Development and Carbon Emission in OIC Countries
Authors: Fajri Mohammad Zen Nasrudin , Amal Ikhsanul , Delawari Abdul Fareed , Suminto Ahmad
Published: July 2024

Economic activities are important factors for the development of countries. However, many countries give too much importance to the economy without paying attention to the country's environment as a result of ongoing economic activities, such as industrial, electricity production, transportation, and commercial and residential which can cause environmental degradation with the spread of CO2 carbon dioxide emissions. The growth of a financial sector that supports those economic activities is considered the driver of carbon emissions at the macro level. However, Islam teaches Muslims to avoid corruption on earth including those leading to the rise in carbon emissions. This makes Muslim-majority countries have better concern in dealing with carbon emissions.  This study aims to analyze the influences of financial institution index (FII) and financial market index (FII) on carbon dioxide emissions in the Organization of Islamic Cooperation member nations. Using the GMM estimator for a panel dataset of 36 countries between 2000 and 2021, this study unravels that the FII significantly increased carbon emissions in OIC countries. In reverse, FMI contributed to the reduction of carbon emissions in OIC countries. This paper recommends the government set regulations for banking sectors to improve eco-friendly credits for the private sector. It is also recommended that the government enrich the issuance of green securities and strengthen the financial market because it is effective in minimizing carbon emissions.
Analisis Ayat-Ayat Kebebasan Beragama dalam Tafsir Sayyid Qutb
Authors: Basri Akhmad Sulton Hasan , Waskito Subarkah Yudi
Published: July 2024

Pada dasarnya kebebasan untuk memilih menjadi mukmin atau kafir merupakan otoritas sepenuhnya dari manusia itu sendiri. Bahkan dalam beragama, harus berdasarkan kepada keyakinan dan kesadaran yang penuh terhadap ajaran dari agama yang dipeluknya. Artikel ini menganalisis tentang pandangan Sayyid Qutb terhadap kebebasan beragama dalam Tafsîr Fî Zhilâl Al-Qur’ân. Metode yang digunakan adalah deskriptif analitis dengan tafsir tematik sebagai pendekatannya. Hasilnya ditemukan bahwa pertama, bahwa kebebasan beragama menurut Sayyid Qutb sangatlah ketat, karena sifat agama Islam sendiri didasarkan pada ayat-ayat Al-Qur'an yang menjelaskan hubungan antara orang-orang yang tidak menganut agama Islam dengan orang-orang yang menganut agama lain, sehingga menetapkan agama Islam sebagai hukum terakhir tentang hubungan antara masyarakat Islam dengan orang-orang yang tidak menganut agama Islam. Kedua, kebebasan beragama dalam Islam adalah bahwasanya tidak ada paksaan dalam beragama. Ketiga, Pada umumnya, para Mufassir menafsirkan ayat-ayat tentang kebebasan beragama berarti bebas untuk bertindak adil dan berhubungan baik dengan orang lain. Hubungan baik tersebut berlaku untuk semua agama, hal ini menunjukkan bahwasanya toleransi yang dimaksud bukanlah dalam ranah aqidah dan ibadah, melainkan cukup toleransi dalam batasan mu'ȃmalah saja.
Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications.
Authors: Barros-Aragão Fernanda G. Q. , Pinto Talita P. , Carregari Victor C. , Rezende Nathane B. S. , Pinheiro Thaís L. , Reis-de-Oliveira Guilherme , Cabral-Castro Mauro J. , Queiroz Daniel C. , Fonseca Paula L. C. , Gonçalves Alessandro L. , de Freitas Gabriel R. , Sudo Felipe K. , Mattos Paulo , Bozza Fernando A. , Rodrigues Erika C. , Aguiar Renato S. , Rodrigues Rosana S. , Brandão Carlos O. , Souza Andrea S. , Martins-de-Souza Daniel , De Felice Fernanda G. , Tovar-Moll Fernanda F.
Published: July 2024

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2’s spike protein in patients’ CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62–62.23 vs. Mild 3.91 pg/mL CI 1.5–10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4–4.4 vs. Non-Pronounced 2.0, CI 1.4–2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89-123.31 vs Non-Pronounced 6.22, CI 2.9-13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.
Biosynthesis of unnatural polyisoprenes by engineered prenyltransferases on rubber particles
Authors: Takahashi Seiji , Suenaga-Hiromori Miki , Ishii Tomoki , Khan Nadia Nur Shazana Binti Abu Talib , Mikami Tomoyo , Takahashi Tomohiro , Minakawa Chiho , Yanbe Fumihiro , Waki Toshiyuki , Nakayama Toru , Imaizumi Riki , Yanai Taro , Kataoka Kunishige , Yamashita Satoshi , Takeshita Kohei , Matsuura Hiroaki , Sakai Naoki , Yamamoto Masaki , Yamaguchi Haruhiko , Miyagi-Inoue Yukino , Fushihara Kazuhisa , Tozawa Yuzuru
Published: July 2024

Natural rubber (NR) is a sustainable biopolymer consisting mainly of cis-1,4-polyisoprene. Modifying an NR biosynthetic enzyme is a promising strategy to bioproduce novel polymers. Here, we have elucidated the NR biosynthetic mechanism and successfully developed novel enzymes that synthesise NR-sized polyisoprenes with unnatural substrates. NR is synthesised by a cis-prenyltransferase (cPT) on rubber particles (RPs), NR-harbouring lipid monolayer membrane organelles. However, the key to NR biosynthesis is not specialised cPTs, but the proper arrangement of cPTs on RPs since cPTs from various non-NR-producing organisms, such as humans, synthesise NR when introduced into the RPs. A tomato cPT, which condenses only one isoprene unit, was engineered to synthesise novel NR-sized polyisoprenes with artificial substrates by modifying residues for product size determination. Furthermore, the introduction of a modified trans-prenyltransferase into RPs led to the synthesis of NR-sized trans-1,4-polyisoprenes. This RP system could be used as a versatile platform for enzymatic polyisoprenoid synthesis.
Automating adjoint sensitivity analysis for multidisciplinary models involving partial differential equations
Authors: Xiang Ru , Schie Sebastiaan P. C. van , Scotzniovsky Luca , Yan Jiayao , Kamensky David , Hwang John T.
Published: July 2024

We present a general framework for incorporating partial differential equation (PDE)- based models into gradient-based optimization of multidisciplinary systems by integrating FEniCSx with the recently-developed Computational System Design Language (CSDL). CSDL is a domain specific language designed to facilitate adjoint sensitivity analysis multidisciplinary design optimization (MDO). We use CSDL’s abstractions to link together sub-models representing different disciplines, not all of which are necessarily modeled by PDEs. For the subsystems which are modeled by PDEs, we use FEniCSx to compute partial derivatives of problem residuals, which CSDL can combine with derivatives from other disciplines using the chain rule and the adjoint method. The development of this framework is motivated by the problem of optimizing designs of electric vertical takeoff and landing (eVTOL) aircraft where, due to the relative novelty of this class of vehicle, there is currently a large, unexplored design space. Predicting the performance of eVTOL aircraft requires PDE-based modeling of various sub-problems, including electric motors, composite shell structures, and thermoelasticity and electrochemistry of battery packs. For system-level analysis and optimization, these must be coupled to non-PDE components, such as low-fidelity aerodynamic models, geometric design tools, and lumped-parameter battery and circuit models. In this work, we demonstrate the modeling flexibility and efficiency of this framework through classic optimal control and topology optimization problems with known solutions, and also challenging eVTOL-related applications including shape optimization of an electric motor, and aeroelastic coupling for gust response of an eVTOL wing. Given the generality of this framework, we expect it to facilitate research on a wide-range of PDEconstrained MDO problems beyond eVTOL applications.
A consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson’s Disease
Authors: Mammen Jennifer , Adams Jamie
Published: July 2024

Background
A comprehensive, widely-accepted, patient-centered conceptual model of Parkinson’s disease (PD) is needed to improve therapeutic development and guide selection of relevant endpoints.
Objectives
To develop an evidence-based conceptual model of early PD, defined as <3 years since clinical diagnosis, that meets the needs of all relevant stakeholders, including people with PD, researchers, clinicians, industry, and regulators.
Method
A multi-stakeholder taskforce and patient advisory panel oversaw the systematic review and meta-synthesis of qualitative and quantitative studies using JBI Mixed Methods Review criteria and GRADE-CERQual standards for assessment of evidence quality, with iterative taskforce and advisory meetings to develop the model.
Results
More than 340 symptoms and impacts were identified from 38 unique study samples. These were grouped into 10 symptom domains (Movement, Cognitive, Psychiatric, Sleep, Sensory, Speech, Digestive, Urinary, Sexual, Autonomic) and two impact domains (Physical functioning, Psychosocial functioning). Synthesis of findings tables (SOFT) indicate that a wide range of motor and non-motor symptoms are prevalent and bothersome in early PD, with strongest evidence for tremor, dexterity, gait, stiffness, and slow movements, as well as cognitive changes (e.g., word finding issues), mood and sleep alterations, urinary dysfunction, constipation, pain, and fatigue. These commonly affected mobility, self-concept, coping, effort of living, interpersonal interactions and important activities, with evidence of many understudied impacts.
Conclusion
This consensus-based conceptual model of early PD provides the most comprehensive catalogue of meaningful symptoms and functional impacts to date. The model and SOFT offer evidence-based tools for identification of concepts of interest to define endpoints for clinical trials.
m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p
Authors: Wang Kefeng , Zhu Chunming , Li Ruiming , You Xiangyun , Xu Jie , Wang Jiahe , Dong Dan , Chen Xiaonan
Published: July 2024

Background: N6-methyladenosine (m6A) has been validated to play a vital role in human cancers. However, the modulation of m6A modification on renal cell carcinoma (RCC) and long non-coding RNA (lncRNA) LHX1-DT is still unknown.
Methods: The m6A levels of RCC tissues and cell lines were detected by colorimetry assay. Differentially expressed lncRNAs and m6A levels were identified by microarray analysis. Functional assays were designed to verify the impacts of lncRNA LHX1-DT (LHX1-DT) on RCC cell proliferation and invasion. The interaction between insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and LHX1-DT was detected by RNA immunoprecipitation and luciferase reporter assays.
Results: LHX1-DT was downregulated in RCC tissues and decreased LHX1-DT expression predicted poor overall survival in RCC patients. Functional experiments uncovered that LHX1-DT overexpression dramatically inhibited cell proliferation and invasion. Mechanistically, METTL14-mediated m6A reader IGF2BP2 could recognize the m6A modification site of LHX1-DT and enhance its stability. LHX1-DT functioned as a competing endogenous RNA (ceRNA) to sponge miR-590-5p, leading to the downregulation of the target programmed cell death factor 4 (PDCD4) to promote RCC cell proliferation and invasion.
Conclusions: LHX1-DT is an independent prognostic biomarker for RCC. The IGF2BP2/LHX1-DT/miR-590-5p/PDCD4 axis inhibits the progression and is a novel therapeutic target.
Exploring the impact of biogenic zinc oxide nanoparticles derived from Lantana camara L. on alleviating heat stress in wheat
Authors: Kapoor Neelesh , Agrawal Ankit , Kumar Prafulla , Kumar Ravindra , Sengar Rakesh Singh , Gangwar L. K. , Kumar Pankaj , Dixit Rekha
Published: July 2024

Wheat faces escalating vulnerability to heat stress as a consequence of climate change, resulting in a substantial annual loss of up to 30% in global wheat productivity. Nanotechnology emerges as a promising frontier, with the potential to revolutionize agriculture across various stages, from seed priming to post-harvest storage. In this study, biogenic zinc oxide nanoparticles (ZnO-NPs) synthesized from Lantana camara leaf extracts was evaluated on growth, morphological, bio physiochemical and molecular parameters in four wheat genotypes. The application of ZnO-NPs, particularly at a concentration of 100 ppm, significantly improved various seed growth parameters and total protein content. Genetic analyses unveiled substantial variability among wheat genotypes under both non-stress and heat-stress conditions. Heritability and genetic advance estimates underscored spike length and grain yield as promising traits. Moreover, genotypic and phenotypic correlations revealed intricate relationships between agronomic traits, providing valuable insights for targeted breeding strategies. Path analysis elucidated the direct and indirect contributions of traits to grain yield, emphasizing the significance of biomass, effective tillers per plant, and spike length. Physiological and biochemical responses indicated that ZnO-NPs alleviated the adverse effects of heat stress on chlorophyll content, photosynthetic rate, relative water content, and cellular membrane stability. Simultaneously, ZnO-NPs enhanced proline, catalase, peroxidase and superoxide dismutase activities. Gene expression analysis of heat shock proteins (HSP17, Hsp23, and Hsp70) in heat-tolerant and heat-sensitive genotypes under various heat shock treatments revealed distinct responses, with HSP17 exhibiting the highest expression in PBW226 under stress conditions. Overall, this research showcases the potential of biogenic ZnO-NPs to enhance wheat resilience in the face of climate change, highlighting nanotechnology's pivotal role in modern agriculture and its contribution to global food security.
Hydro-mechanical theoretical solutions of supported noncircular excavated in deep elastic ground
Authors: Wang E. T. , Wang H. N. , Song F. , Jia X. C.
Published: July 2024

This study provides a general analytical approach to predict the stresses and displacements of deep noncircular tunnels excavated in saturated elastic ground, considering the hydro-mechanical coupling, the interaction between rock and liner, and arbitrary tunnel shapes. The complex variable theory is innovatively extended to solve the seepage fields for noncircular supported tunnels in both surrounding rocks and liner fields. After that, coupled hydro-mechanical solutions of stresses and displacements can be determined by considering the influence of seepage flow on the mechanical responses. Furthermore, stability analyses of supported tunnels are conducted in the hydro-mechanical coupled framework, incorporating the effect of seepage flow. As a verification, a good agreement is observed between stress and displacement fields obtained from the current analytical solutions and numerical simulations. Then, parametric analyses are performed to assess how variations in tunnel shape, liner permeability, and liner thickness influence the mechanical behaviours of supported tunnels. Meanwhile, by employing the Mohr-Coulomb strength criterion, an expression of equivalent stress is proposed to assess the potential failure behaviour of supported tunnels in the entire process of excavation and operation stages. This study provides high potential of application to a number of relevant case studies, such as tunnelling below the water table.
Transformer-based modeling of Clonal Selection and Expression Dynamics (TraCSED) reveals resistance signatures in breast cancer
Authors: Hafner Marc , Maulding Nathan , Zou Jun , Zhou Wei , Metcalfe Ciara , Stuart Joshua , Ye Xin
Published: July 2024

Understanding transcriptional heterogeneity in cancer cells and its implication for treatment response is critical to identify how resistance occurs and may be targeted. Such heterogeneity can be captured by in vitro studies through clonal barcoding methods. We present TraCSED (Transformer-based modeling of Clonal Selection and Expression Dynamics), a dynamic deep learning approach for modeling clonal selection. Using single-cell gene expression and the fitness of barcoded clones, TraCSED identifies interpretable gene programs and the timepoints at which they are associated with clonal selection. When applied to cells treated with either giredestrant, an estrogen receptor (ER) antagonist and degrader, or palbociclib, a CDK4/6 inhibitor, time-dependent resistance pathways are revealed. For example, ER activity is associated with positive selection around day four under palbociclib treatment and this adaptive response can be suppressed by combining the drugs. Yet, in the combination treatment, one clone still emerged. Clustering based on partial least squares regression found that high baseline expression of both SNHG25 and SNCG genes was the primary marker of positive selection to co-treatment and thus potentially associated with innate resistance – an aspect that traditional differential analysis methods missed. In conclusion, TraCSED enables associating pathways with phenotypes in a time-dependent manner from scRNA-seq data.
Evidence of Partial Artemisinin Resistance in Malaria Endemic Lake Region, Busia County, Western, Kenya
Authors: Makau Mark , Kanoi Bernard N. , Mgawe Calvin , Maina Michael , Too Edwin , Naruse Taeko , Abkallo Hussein , Waweru Harrison , Adung’o Ferdinand , Kaneko Osamu , Gitaka Jesse
Published: July 2024

Malaria remains a key health and economic problem particularly in sub-Saharan Africa. The emergence of artemisinin resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because ART remains the first-line treatment drug in the majority of malaria-endemic regions in Sub-Saharan Africa. P. falciparum ART resistance has been linked to mutations in the Kelch – 13 propeller gene (k13) of the Plasmodium falciparum. Single nucleotide polymorphisms in the K-13 region have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of K-13 mutations in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were put under directly observed treatment with Artemether-Lumefantrine (AL), and microscopy repeated after 24 hours. P. falciparum DNA from samples showing the lowest 24-hour relative parasite clearance underwent targeted amplification of the K-13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R nonsynonymous mutation C469Y was identified in 3% (n = 3) of the samples suggesting it could have had an impact on clinical parasite clearance 24 hours post-AL administration. Our findings highlight the need for continuous surveillance of AL resistance in western Kenya and the region to determine the spread of ART-R and inform containment.
Sexual and reproductive health interventions for adolescents in Niger: Historical overview and stakeholder profile Health
Authors: Ibrahim Nassirou , Silva Roxane Borgès Da , Diarra Aïssa , Agyepong Irene Akua
Published: July 2024

Background
In many developing countries such as Niger, a variety of interventions have been implemented to improve adolescent sexual and reproductive health. Nevertheless, the reality is that the levels of adolescent sexual and reproductive health (ASRH) indicators remain critical in these countries. Unfortunately, very few studies have examined the reasons why these interventions fail. This study aimed to improve the knowledge on this topic. Specifically, it described the history of ASRH interventions and examined the profile of the actors who contributed to the emergence of these interventions in Niger.
Methods
A literature review was first conducted covering the period 1975–2021. Then, individual interviews were conducted with 46 actors involved in the process of designing, financing, and implementing ASRH interventions in Niger. For the data analysis, a descriptive historical approach was carried out using an analysis grid to exploit the information collected. Qualitative data were transcribed and coded using Nvivo 12 software, and a content analysis was carried out.
Conclusion
Several interventions have been implemented to improve the sexual and reproductive health of adolescents in Niger since 1994, but their impact is questionable.
Functional Connectivity Changes in Human Brain Networks from 2 Hz Rhythmic Muscle Contraction to the Hand: A pilot study
Authors: Stauber William , McGaughey Tyler , Evans Nick , Chaffin Alyssa , Snyder Sean , Webster Paula J. , Sizemore Gina , Brefczynski-Lewis Julie A. , Lewis James W.
Published: July 2024

For patients undergoing prolonged bed rest, inactivity results in a decline in multiple physiological systems that can be attenuated by physical exercise in the hospital such as walking. In addition, non-voluntary activation of skeletal muscles can produce some benefits similar to walking. We hypothesize that rhythmical muscle stimulation of small muscles of the hand, in contrast to sensory stimulation of the skin, will lead to patterns of functional connectivity in the brain that reflect central mechanisms behind some of the physiological benefits afforded by exercise. Using a 2x2 design, healthy participants (age 21 to 31) underwent resting-state functional magnetic resonance imaging (rsfMRI) immediately before and after a45 minute treatment with either muscle stimulation (2 Hz) or skin stimulation (100 Hz) to the left hand. Six of eight participants responded to the rhythmical muscle contractions in a manner consistent with endorphin release. Functional connectivity data were analyzed using CONN toolbox software. Relative to skin stimulation, rhythmic muscle stimulation led to significant differences in connectivity with regions associated with the autonomic and limbic systems, including the hypothalamus, amygdala, periaqueductal grey, thalamus, basal ganglia, plus insulae and cingulate cortices. In addition, the rhythmic muscle stimulation led to changes in several previously identified resting state networks. In conclusion, distinct networks of the human central nervous system appear to play roles in the outcomes reported for therapeutic use of rhythmical muscle stimulation of hand muscles. These outcomes support the use and future development of similar treatment protocols for bedridden patients or people unable to engage in daily exercise.
The Origin of Patient-Derived Cancer Organoids from Pathologically Undiagnosed Specimen in Patients with Pancreatobiliary Cancers
Authors: Kim Bomi , Park Jiho , Na Hee Young , Park Sinwoo , Jin Jeonghwa , Jung Kwangrok , Lee Jong-chan , Hwang Jin-Hyeok , Seo Minseok , Kim Jaihwan
Published: July 2024

Purpose
Tissue confirmation of pancreatobiliary cancer is often difficult because of the location of the tumor and structure of the surrounding blood vessels. Patient-derived cancer organoids (PDCOs) reflect the genomic characteristics of individual cancers. Although diverse attempts to construct PDCOs for various pancreatobiliary cancer models are ongoing, no research results have yet confirmed the possibility of performing a precise diagnosis on PDCOs derived from pathologically negative patient samples.
Methods
We obtained a total of nine samples, including pathologically negative samples, from four patients (three patients with pancreatic cancer and one patient with gallbladder cancer) using different tissue acquisition methods to establish PDCOs (success rate 75%).
Results
We successfully verified whether the constructed PDCOs could represent the tissues of patients with pancreatobiliary cancer at each multi-omics level using tumor panel sequencing, single-cell RNA sequencing, hematoxylin and eosin, and immunohistochemical staining. PDCOs from pathologically negative samples showed expression patterns of malignant ductal cell-related biomarkers similar to those of other pathologically positive samples. Furthermore, the expression patterns at the single-cell level in PDCO from patients ultimately diagnosed with gallbladder cancer after surgery were different from those in patients with pancreatic cancer.
Conclusion
Therefore, PDCOs could be used for precision therapy from positive as well as negative samples.
Equation Development for Predicting Phreatic Line in Silty Clay Soils under Groundwater Inundation
Authors: Alsaffar Abdul Kareem Khaleel , Hamad Riyadh , Majeed Zaid Hameed , Alsareji Osamah J.
Published: July 2024

The threat of rising groundwater inundation, estimated by the elevation of the water table above the ground surface, is highly impacting various infrastructure Components. That issue can potentially damage Critical infrastructure elements such as foundations of buildings, bridges, roads, and other essential aspects. This problem will intensify when it is linked to the growing frequency of severe weather events and alterations in land use, which increases groundwater withdrawals. Among others, the important goal is to understand groundwater inundation and its effects on infrastructures (footings and soil), find methodologies for vulnerability evaluation and damage mitigation, and highlight the significant challenges and opportunities for future research. A laboratory model was constructed to simulate the actual conditions. A seepage of high-water level through Silty Clay Soil was tested to determine an equation of a phreatic line in such homogenous soil. A unitless relationship was estimated to represent the equation of the parabolic curve of the phreatic line ( Y2/H2 = 1-X/L), and it was successfully applied after being tested statistically in two methods (1) R2 formula (0.97–0.99); (2)RMSE method (average 0.69), (0–1). To track the change in parameters, the following two parameters were taken in the analysis: 1- Type of soil (silty clay soil) 2- Height of water table.
Enhancing Critical Current Density in Thin Superconductor Layers by Moiré Pinning Centers
Authors: Owjifard Zahra , Tavana Ali , Hosseini Mehdi
Published: July 2024

One important factor affecting the critical current density in type-II superconductors is the formation of artificial pinning centers. Hence, the engineering of pinning centers in superconducting systems has garnered considerable attention. In this study, the effect of moiré patterned pinning centers on the critical current density of superconducting tapes is investigated. The Langevin equation is solved by taking into account the prominent forces within the superconductor medium, using the appropriate boundary conditions for vortices. The vortex dynamics is investigated by performing molecular dynamics simulations, which are used to calculate the corresponding critical current densities. Results show a significant enhancement in the critical current density at particular angles of the relative rotation of the primary lattices. It is also revealed that for stronger pinning forces, the calculated critical current densities are higher in the moiré lattices compared to the primary lattices of pinning centers.
Enhancing Doctor-Patient Communication Using Large Language Models for Pathology Report Interpretation
Authors: Yang Xiongwen , Xiao Yi , Liu Di , Zhang Yun , Deng Huiyin , Huang Jian , Shi Huiyou , Liu Dan , Liang Maoli , Jin Xing , Sun Yongpan , Yao Jing , Zhou XiaoJiang , Guo Wankai , He Yang , Tang WeiJuan , Xu Chuan
Published: July 2024

Background
Large language models (LLMs) are increasingly utilized in healthcare settings. Postoperative pathology reports, which are essential for diagnosing and determining treatment strategies for surgical patients, frequently include complex data that can be challenging for patients to comprehend. This complexity can adversely affect the quality of communication between doctors and patients, potentially impacting patient outcomes.
Materials and Methods
This study analyzed text pathology reports from four hospital between October and December 2023, focusing on malignant tumors. Using GPT-4, we developed templates for interpretive pathology reports (IPRs) to simplify medical terminology for non-professionals. We randomly selected 70 reports to generate these templates and evaluated the remaining 628 reports for consistency and readability.
Results
Among 698 pathology reports analyzed, the interpretation through LLMs significantly improved readability and patient understanding. The average communication time between doctors and patients decreased by over 70%, from 35 minutes to 10 minutes (P < 0.001), with the use of IPRs. The study also found that patients scored higher on understanding levels when provided with AI-generated reports, from 5.23 points to 7.98 points (P < 0.001), with the use of IPRs. indicating an effective translation of complex medical information.
Conclusion
This research demonstrates the efficacy of LLMs like GPT-4 in enhancing doctor-patient communication by translating pathology reports into more accessible language. By improving comprehension and reducing communication time, AI applications in medical settings can enhance patient outcomes and satisfaction, highlighting the potential of AI to bridge gaps between medical professionals and the public in healthcare environments.
Methylation assay in KMT2B related dystonia: a novel diagnostic validation tool
Authors: Carvalho Gleyson Francisco da Silva , Gusmão Claudio Melo , Wolff Beatriz Martins , Vieira Lucas Liro , Gasparini Yanca Oliveira , Costa Mariana Ribeiro , Mendes Rafaela Silva , Castro Matheus Augusto Araujo , Sakuma Mayara T , Kok Fernando , Kulikowski Leslie Domenici
Published: July 2024

Background/Objectives: KMT2B-related dystonia (DYT28, OMIM #617284), is a progressive neurological condition characterized by early-onset movement disorders with autosomal dominant inheritance. In this study, we describe the use of a genome methylation epi-signature methodology to functionally validate 2 variants of uncertain significance (VUS) in the KMT2B gene.
Methods: Genome-wide methylation status was assessed using the EPIC methylation assay in peripheral blood samples from two subjects with early-onset movement disorder and missense variants of uncertain significance in the KMT2B gene (p.Leu1720Phe and p.Tyr2515Cys). After QC and normalization steps, we compared the M-values for all 144 probes, previously described as an EpiSign for KMT2B-related dystonia, between the two subjects and 14 controls individuals.
Results: The individual harboring the p.Tyr2515Cys variant exhibited a hypermethylation profile compatible with pathogenic/likely pathogenic variants in KMT2B, allowing for variant reclassification, conclusive genetic counseling, and patient stratification for deep brain stimulation. In contrast, the individual harboring the p.Leu1720Phe variant had a methylation status similar to controls, practically ruling out KMT2B-related dystonia.
Conclusion: Investigation of methylation status can be a powerful tool to determine pathogenicity when facing KMT2B variants of uncertain significance. Methylation results may optimize genetic counseling and positively impact patient care.
One-Year Outcomes of a Digital Twin Intervention for Type 2 Diabetes: A Retrospective Real-World Study
Authors: Shamanna Paramesh , Erukulapati Ravi Shankar , Shukla Ashutosh , Shah Lisa , Willis Bree , Thajudeen Mohamed , Kovil Rajiv , Baxi Rahul , Wali Mohsin , Damodharan Suresh , Joshi Shashank
Published: July 2024

This retrospective observational study, building on prior research that demonstrated the efficacy of the Digital Twin (DT) Precision Treatment Program over shorter follow-up periods​​, aimed to examine glycemic control and reduced anti-diabetic medication use after one year in a DT commercial program. T2D patients enrolled had adequate hepatic and renal function and no recent cardiovascular events. DT intervention powered by artificial intelligence utilises precision nutrition, activity, sleep, and deep breathing exercises. Outcome measures included HbA1c change, medication reduction, anthropometrics, insulin markers, and CGM metrics. Of 1985 enrollees, 132 (6.6%) were lost to follow-up, leaving 1853 participants who completed one year. At one year, participants exhibited significant reductions in HbA1c [mean change (SD) -1.8 (1.7)%, p<0.0001], with 1650 (89.0%) achieving HbA1c levels below 7%. At baseline, participants were taking mean anti-diabetic medications of 1.9 (1.4) which decreased to 0.5 (0.7) after one year [change: -1.5 (1.3), p<0.0001]. There were also significant decreases in weight [-4.8 (6.0) kg, p<0.0001], improvements in insulin resistance as measured by HOMA2-IR [-0.1 (1.2), p=0.00005], and enhancements in β-cell function [HOMA2-B; +21.6 (47.7); p<0.0001], along with better CGM metrics. These findings suggest that DT intervention could play a vital role in the future of T2D care.
A potential clue of IL-17A as a helper assist paraquat and T cell infiltration into brain parenchyma
Authors: Shi Ge , Wang Kaidong , Hu Rong , Li Yang , Jiao Yuxuan , Li Yonghang , Li Yujing , Qi Ai , Huang Min
Published: July 2024

Paraquat (PQ), a globally widely used and highly residual herbicide, is one of the potential environmental risk factors for neurodegenerative diseases (NDs). Before exerting neurotoxicity, however, PQ needs to break through the blood-brain barrier (BBB), how it penetrates the BBB and reaches the brain parenchyma remains a mystery. Recently, peripheral T cells and cytokine infiltrates into the brain have been involved in the development of NDs. But, the main reason for the infiltrating is not yet unrevealed. BBB plays a crucial role in the communication of T cells between the central nervous system (CNS) and the peripheral. Hence, whether T cells and their cytokines serve as core assistants to assist PQ infiltrating the BBB exerting neurotoxicity, in this article, C57BL/6J mice treated with PQ experienced down emotion and learning and memory abilities decreased. Pathologically, neurons and microglia respectively exhibit selective spatial damage and hyperresponsiveness. Simultaneously there were capture the traces of CD3 and its subsets of CD4/8, as well as IL-17A. Surprisingly, the response of T cells from peripheral blood and spleen to PQ gradually leans towards Th17 cells and secretes IL-17A. Therefore, it is highly suspected that IL-17A plays a role in disrupting the BBB. In vitro, bEnd.3 cells were specifically constructed with IL-17A, and PQ or mixture revealed IL-17A takes part in PQ-induced BBB disruption. Altogether, PQ responds to peripheral T cells to react and secrete IL-17A, which destroys BBB and assists PQ and T cells or other factors in infiltrating brain parenchyma.
FOCUS-MUSE DWI in Primary Rectal Cancer: Comparison with FOCUS, MUSE, and Single-shot DWI
Authors: Feng Weiming , Zhu Lan , Wang Kangning , Dai Jiankun , Ma Qianchen , Shen Hailin , Yuan Fei , Zhang Huan
Published: July 2024

Background
To assess the reliability of constrained undistorted single-shot diffusion-weighted imaging (FOCUS_DWI), multiplexed sensitivity-encoding_DWI (MUSE_DWI), single-shot echo planar imaging DWI (SS_DWI) and the combination of FOCUS and MUSE (FOCUS-MUSE_DWI) in primary rectal cancer by evaluating image quality and T staging performance.
Methods
Patients with primary rectal cancer underwent 3.0T MR scans with four DWI sequences. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values were measured. T stage and subjective image quality were assessed. Statistical analyses included intraclass correlation coefficient (ICC), Fleiss Kappa test, Friedman test, Chi-square tes, Paired t-test, and Spearman correlation analysis.
Results
A total of 45 patients (mean age: 60.45 ± 9.79, 30 men) were evaluated. FOCUS-MUSE_DWI exhibited the highest CNR (6.43 ± 0.94 and 6.44 ± 0.90 for two readers, respectively), adequate SNR (49.81 ± 6.60 and 49.67 ± 6.09 for two readers, respectively) with the best ADC repeatability (mean absolute difference: 8.44). No significant T staging differences were observed among DWI sequences (p ≥ 0.908). FOCUS-MUSE_DWI achieved the highest total image quality score (median value: 16) compared with other three sequences (p ≤ 0.001). Good to excellent agreement observed in both interobserver and intraobserver assessments (kappa > 0.600).
Conclusion
FOCUS-MUSE_DWI demonstrated good reliability with commendable T staging performance, the best ADC repeatability, sufficient SNR, the best CNR among four DWI sequences and could be the recommended sequence for clinical evaluation.
Resilience in a time of stress: revealing the molecular underpinnings of coral survival following thermal bleaching events
Authors: Nunn Brook , Brown Tanya , Timmins-Schiffman Emma , Mudge Miranda , Riffle Michael , Axworthy Jeremy , Dilworth Jenna , Kenkel Carly , Zaneveld Jesse , Rodrigues Lisa , Padilla-Gamiño Jacqeline
Published: July 2024

Coral bleaching events from thermal stress are increasing globally in duration, frequency, and intensity. Bleaching occurs when a coral’s algal symbionts are expelled, resulting in a loss of color. While bleaching can result in mortality, some corals survive, reacquire their symbionts, and recover. In this study, we experimentally bleached Montipora capitata to examine molecular and physiological signatures of intrinsic differences between corals that recover (resilient) compared to those that die (susceptible). All corals were collected from the same bay and monitored for eight months post-bleaching to identify genets exhibiting long-term resilience and survival. Using an integrated systems-biology approach that included quantitative mass spectrometry-based proteomics, 16S rRNA of the microbiome, total lipids, symbiont community composition and density, we explored molecular-level mechanisms of tolerance in experimental corals pre- and post-bleaching and identified predictive biomarkers of resilience that distinguish resilient and susceptible corals before thermal-induced bleaching events. Prior to thermal stress, resilient corals were characterized by a more diverse microbiome and increased abundances of proteins essential for carbon and nitrogen acquisition strategies, symbiont retention and acquisition, and pathogen resistance. Susceptible corals had early signs of symbiont rejection and had resorted to using urea uptake pathways for carbon and nitrogen. Further, proteins identified prior to bleaching were amplified after bleaching, suggesting these pathways may be deterministic of a coral’s fate when thermally bleached. Our results have important implications for the future of reefs, revealing molecular factors necessary for surviving thermally-induced bleaching events and identifying promising diagnostic biomarker candidates for coral reef management and restoration applications.