bluuebunny/crossref_metadata_2025 huggingface dataset:
CAN CORPORATE SUSTAINABILITY PERFORMANCE (CSP) OVERCOME INDONESIA'S CORPORATE DEBT PROBLEMS?
Authors:   PPM School of Management, Febrian Johnson Ferry , Hendriyeni Nora Sri ,   PPM School of Management
Published: May 2024

Based on IMF publications (2022), Indonesian companies have a risky debt level that may cause bankruptcy, so companies are required to make leverage adjustments to return the debt to its optimal level. In recent years, corporate sustainability performance (CSP) practices have been proven to improve performance and overcome financial problems such as debt by integrating sustainability aspects into business processes. Based on stakeholder theory and trade-off theory, this study aims to examine the effect of CSP on leverage adjustment and the role of competitive advantage, equity mispricing, profitability, and firm size in moderating this relationship. This study used a sample of 40 listed companies that registered on the Indonesia Stock Exchange and implemented CSP from 2019 to 2022. By using multiple linear regression analysis and moderated regression analysis, this study shows that companies with CSP can increase company leverage adjustments. Meanwhile, company characteristics such as equity mispricing and company size have proven to strengthen this relationship, but competitive advantage and profitability do not influence it. The results of this study provide theoretical and practical benefits by enhancing knowledge about CSP and leverage adjustments, as well as enabling managerial and regulatory parties to make the right decisions.
BEYOND THE NUMBER: TONE ANALYSIS IN ANNUAL REPORTS
Authors:   Universitas Negeri Malang, Suryani Ani Wilujeng , Fauz Dinda Tustika Apta ,   Universitas Negeri Malang
Published: May 2024

In making decisions, stakeholders utilize not only quantitative information but also qualitative information, such as annual reports. However, annual reports in narrative form are often used to exaggerate company performance data. One aspect that influences stakeholders’ decision is tone. This study aims to examine the impact of positive tone disclosure in management analysis reports and discussions on company value. This study was conducted on 166 financial and property companies listed on the IDX. Management analysis and discussion reports were categorized according to their tone. Using linguistic inquiry and word count software (LIWC-22), the procedure yielded more precise and consistent analysis. Financial data used to determine the value of company was the price-to-book-value (PBV) ratio. The results of the test using robust regression analysis showed that the positive tone disclosure with an informative nature had a positive influence on the company’s value. This finding suggests that managers must use positive tones when regulating the company's situation in order to maintain the expected value of company.
ESG PERFORMANCE, DEBT EQUITY CHOICES, AND RAPID ADJUSTMENTS IN INDONESIA
Authors:   Universitas Selamat Sri, Pujiastuti Arum , Yunita Rizki Dini Shandra ,   National Yunlin University of Science and Technology, Astuti Fitria Yuni ,   Universitas Selamat Sri
Published: May 2024

Previous research has explored the relationship between sustainability performance and firm performance; however, there is a noticeable scarcity of studies addressing the intricate connection between sustainability performance and firm financing. This study aims to bridge this gap by investigating how sustainability performance impacts firm financing decisions and capital structure adjustment in the context of Indonesia. Leveraging Environmental, Social, and Governance (ESG) performance data specific to Indonesia, this research contributes novelty to financing choices and the speed at which firms adjust their leverage. Through a combination of fixed-effect modelling and dynamic panel Generalized Method of Moments (GMM), the study employs a dataset containing 506 firm-year observations, evenly distributed between ESG firms and non-ESG firms. The findings demonstrate that firms that incorporate ESG principles into their operations display a greater inclination towards equity financing. Additionally, the research underscores that ESG firms exhibit a more rapid adjustment pace toward their target leverage ratios compared to non-ESG firms.
Preexposure Prophylaxis (PrEP) for HIV Prevention at Outpatient Substance Use Treatment Facilities, United States, 2021
Authors: Bunting Samuel R. , Vidyasagar Nitin , Wilson Allison P. , Hazra Aniruddha
Published: May 2024

Objectives. To determine the percentage of US outpatient substance use treatment facilities that offer HIV preexposure prophylaxis (PrEP).

Methods. We used a retrospective cross-sectional design with data from the National Substance Use and Mental Health Services Survey, which was administered to directors of US outpatient substance use treatment facilities in 2021. We evaluated the percentage of outpatient substance use treatment facilities offering PrEP and factors associated with the likelihood of offering PrEP.

Results. We included 12 182 outpatient substance use treatment facilities. Of these, 637 (5.2%) offered PrEP. Offering HIV treatment (adjusted odds ratio [AOR] = 45.3; 95% confidence interval [CI] = 36.0, 56.9) and offering programs for LGBTQ (lesbian, gay, bisexual, transgender, and queer or questioning) people (AOR = 1.3; 95% CI = 1.0, 1.6) were associated with higher likelihoods of offering PrEP.

Conclusions. PrEP is highly effective and recommended for patients at risk for HIV from injection drug use. Nearly 95% of US outpatient substance use treatment facilities did not offer PrEP—a missed opportunity for harm reduction through primary HIV prevention.

Public Health Implications. Diversification of the array of available HIV PrEP options and the ongoing HIV and opioid use epidemics require outpatient substance use treatment facilities to expand PrEP availability. ( Am J Public Health. 2024;114(8):833–837. https://doi.org/10.2105/AJPH.2024.307699 )
Reliability of Hip Strength Assessment in Young Active People with Hip Dysplasia: An Examination in Student Circus Artists
Authors: Ganderton C , O’Brien MJM , Han J , Wallis AK , Munro D , O'Shea T , Grabinski R , King MG
Published: May 2024

BACKGROUND: Developmental dysplasia of the hip (DDH) is common in performing artists and other young active individuals and involves abnormalities in bony morphology of the acetabulum and proximal femur that can negatively impact walking biomechanics, muscular strength, quality of life,
and sleep. Rehabilitation for hip-related conditions should target known modifiable impairments such as hip muscle strength, though a reliable method of assessment in this population remains unclear. OBJECTIVE: To determine the inter- and intra-rater reliability of hip muscle strength assessments
using handheld dynamometry (HHD) in young active circus artists with DDH. METHODS: Reliability of hip strength in all planes was assessed using HHD in 21 adult performing circus arts students (mean age 21.3 yrs [3.2]; 13 M, 5 F, 3 NB) with symptomatic radiologically and clinically diagnosed
hip dysplasia. The reliability of average peak force and absolute peak force were expressed for each position tested. Reliability was assessed using intraclass correlation coefficients (ICC) with standard error of measurement (SEM) and minimal detectable change (MDC) values calculated to improve
clinical interpretability. RESULTS: Good to excellent inter-rater reliability resulted for all hip muscle strength testing positions, ICC=0.88 (95%CI 0.70 to 0.95) to ICC=0.97 (0.92 to 0.99), except average peak hip flexion strength, ICC=0.71 (0.28 to 0.88). Absolute peak hip abduction, ICC=0.77
(0.16 to 0.94), and adduction strength, ICC=0.72 (–0.55 to 0.92), demonstrated the lowest intra-rater reliability. Transverse plane strength measures (rotation) produced the lowest SEM and MDC values followed by the frontal plane (abduction/adduction) and sagittal plane (flexion/extension).
CONCLUSION: HHD is an appropriate and reliable method to assess hip muscle strength in circus artists with DDH.
Comparison of Perfectionism Between Music and Medical Students and its Association with Anxiety
Authors: Alpheis Stine , Altenmüller Eckart
Published: May 2024

OBJECTIVES: Perfection is a central goal for many musicians and health professionals. The present study compared perfectionism between music and medical students to examine whether perfectionism is adaptive or maladaptive and how it evolves during university studies. Furthermore, the
association between perfectionism and anxiety was investigated in both populations to determine possible implications for mental and general health. METHODS: 110 music students (61 F, avg age 23.2 yrs) and 281 medical students (209 F, avg age 23.3 yrs) took part in the study. Perfectionism
was surveyed using two multidimensional perfectionism scales and anxiety was measured using the State-Trait-Anxiety-Inventory. Subscales and total scores of the perfectionism scales were compared within and between groups and correlated with the anxiety measures. RESULTS: Music and medical
students did not differ in their level of perfectionism. However, music students in the early semesters showed significantly (p = 0.009) stronger maladaptive perfectionism (mean 0.3, SD 1.4) than students from more senior semesters (–0.3, 1.7). Musicians from early semesters also scored
higher on “parental expectations and criticism” (p = 0.04), showed more “concerns over mistakes and doubts” (p = 0.009), and perfectionism in general (p = 0.01). Analysis of the anxiety measure showed a strong correlation (rs = 0.55) between maladaptive perfectionism
and anxiety for the music students. Semester and age had no influence on anxiety. Maladaptive perfectionism and adaptive perfectionism both correlated significantly with anxiety in medical students. CONCLUSION: Music and medical students had similar levels of perfectionism. Medical students
maintained a consistent level of perfectionism throughout their studies, while music students were more perfectionistic at the beginning of their education. For both groups, perfectionism was significantly correlated with anxiety.
Serat Wulangreh: Islamization In Java ‎Through Cultural Approach
Authors: Muslih Mustopa
Published: May 2024

Pakubuwana IV combined Islamic teaching and Javanese culture on Serat Wulangreh without eliminating the core value of Islamic teaching its result. Pakubuwana IV used the Javanese language as a communication tool to distribute his message of advice through The Macapat song. Substantially, Wulangreh is Islamic teaching taken from The Al-Quran and Hadith which cover the aspects of divinity, law, ethics, virtue, and social relationship aspect. Although Serat Wulangreh employs local language and culture, it displays identifiable pure Islamic teaching. The teachings on Wulangreh are the forms of acculturation of Islam and Javanese culture. They are applicable in a pluralistic society as a form of multiculturalism emphasizing equality and equity within a diverse and dynamic community (tribes, ethnicities, cultures, and religious beliefs
On the Graph-Based Extension of the Set Based Model: A New Approach on Graph Representation and Model Ensemble
Authors: Kalogeropoulos Nikitas Rigas , Skamnelos Nikolaos , Makris Christos
Published: May 2024

The purpose of this paper is to present a set of algorithmic improvements upon an extension of the Set-Based Model (Kalogeropoulos et al (2020)) that focuses on the dependence among document terms employing graph representations. A graph-based approach to document representation can positively affect the information retrieval process due to the ability of graphs to capture the syntactic notion and, in some cases, the semantic relationship among document terms. The aforementioned model generates complete graphs; thus, each document term will be interdependent with the rest. Consequently, an interdependent segment or multiple parts of a document called a window is defined, in which the graph creation algorithms are applied. The proposed methods aim to approximate the window size by exploiting the document length. Moreover, an attempt to create multiple windows is made, considering the relationship between a sentence and a paragraph, which is reflected in the semantic importance of nodes and edges. An attempt to tackle the stop-word detection problem on bridge nodes is made by implementing algorithmic schemes that use core decomposition (Seid-man (1983a)) to identify the importance of such nodes in a sample of the corpus collection. Finally, a simple reranking scheme and an ensemble voting technique are implemented to enhance model performance on queries where the proposed approach lacks performance. The experimental analysis made on multiple document collections exhibits performance improvements and in some queries, our 1 approach outperforms even state-of-the-art models such as BM25 (Robertson et al (2004)) and ColBERT (Khattab and Zaharia (2020)).
Multiplexed Detection of Respiratory Virus RNA Using Optical pH Sensors and Injection Molded Centrifugal Microfluidics
Authors: Nagl Stefan , Suarez Gianmarco , Tang Yuki , Bayer Steevanson , Cheung Peter
Published: May 2024

Infectious pathogens, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are a threat to global health and prosperity, with the coronavirus disease 2019 (COVID-19) pandemic causing deaths and negative economic impacts worldwide. Pathogens continuously mutate, evading vaccines and treatments; monitoring is therefore crucial to preventing future outbreaks. But there are still many shortcomings in available diagnostic technologies, and scalable and convenient point-of-care technologies are highly demanded. In this work, we demonstrate the application of injection molded centrifugal microfluidic chips with integrated optical pH sensors for multiplexed detection of SARS-CoV-2, influenza A, and influenza B RNA. The optical pH sensors generated sensitive fluorescent readouts from diagnostic reverse transcription loop-mediated isothermal amplification (RT-LAMP) reactions; limits of detection for influenzas A and B, and SARS-CoV-2 of 89, 245, and 38 RNA copies per reaction, respectively, were attained. Results were obtainable within 44 minutes for SARS-CoV-2 and influenza A, and 48 minutes for influenza B. We implemented a data processing strategy that allowed for reliable, quantitative thresholds for deciding reaction outcomes based on numerical derivatives of the fluorescence curves, enabling 100% specificity. This work demonstrates the utility of optical pH sensors and injection molded centrifugal microfluidics for multiplexed infectious disease diagnostics with point-of-care applications.
Midkine is a Potential Novel Biomarker for Acro-osteolysis in Systemic Sclerosis
Authors: Gogulamudi Venkateswara R , Adeogun Ganiat , Donato Anthony J. , Petrey Aaron , Wood Sarah , Zent Roy , Frech Tracy M.
Published: May 2024

Background: Digital acro-osteolysis can result from ischemia and is a complication of systemic sclerosis (SSc). Midkine (MK) is an angiogenic growth factor that plays a key role in bone remodeling. The objective of this study was to examine serum MK level as a biomarker of acro-osteolysis in SSc.
Methods: The study population consisted of patients who consented to undergo ethics approval at two institutions and had Raynaud's phenomenon (RP), abnormal capillaroscopy, and hand radiographs. Age- and sex-matched healthy controls without hypertension, Raynaud phenomenon, or digital lesions were included. Serum MK concentration was measured using an enzyme-linked immunosorbent assay. An analysis of variance test assessed the differences in MK concentrations among SSc patients with acro-osteolysis, SSc patients without acro-osteolysis, and age-and sex-matched healthy controls.
Results: A total of 54 SSc registry patients and 20 age-sex matched healthy controls were included in the cross-sectional analysis of MK levels. Except for digital ulcers, there were no sociodemographic or clinical features that were statistically significantly associated with the presence of acro-osteolysis. There were significantly higher MK levels between SSc without acro-osteolysis than in acro-osteolysis (p=0.0001), as well as in SSc without acro-osteolysis and in healthy controls (p=0.01). There were no significant differences between SSc patients with acro-osteolysis and healthy controls (p=0.31).
Conclusions: Our study suggests that MK may maintain an intact digital tip in SSc patients. A reduction in serum MK level is associated with progressive digital vasculopathy,defined by the presence of acro-osteolysis.
Author Contributions: TMF, VG, GA, AJD, SW, RZ contributed to the design and implementation of the research analysis of the results and to the writing of the manuscript. TMF conceived the original and supervised the project.
EIF6 conditions drug-tolerant persister-like transdifferentiation in small cell lung carcinoma
Authors: Shen Shensi , Peng Haoning , Wang Zhile , Wang Mengyao , Tang Xinpu , Li Kaixiu , Yu Xuejiao , Song Siyang , Wang Yuqing , Lu Tianjian , Dong Bo , Wang Youyu , Chen Minqi , Ceng Dongjian , Deng Yulan , Xia Liang , Guo Chenglin , Pu Qiang , Li Lu , Cerezo Michael , Wang Weiya , Liu Lunxu
Published: May 2024

Drug-tolerant persister cells withstand treatments by adapting their identity through lineage-dependent plasticity during systemic anti-cancer therapies. This phenomenon is evident in small-cell lung carcinoma (SCLC), a lethal neuroendocrine cancer initially responsive (60-80%) to platinum-based chemotherapy but succumbing to resistance within 6 months in advanced stages. This resistance associates with the transdifferentiation of residual tumour cells into a non-neuroendocrine state, a process intricately tied to SCLC's chemotolerance, yet molecular mechanisms governing this lineage conversion remain completed understood. Here we report that first-line chemotherapy induces translation initiation factor eIF6 in drug-tolerant persister-like cells in SCLC, associating with the non-neuroendocrine state in both SCLC genetically engineered mouse model and patient samples. Intervening eIF6 inhibits non-neuroendocrine transdifferentiation, thus enhancing SCLC responsiveness to chemotherapy. Mechanistically, therapy-induced eIF6 dissociates from ribosomes whereas interacts with the extracellular matrix complex CD104/FAK, leading to the activation of MAPK pathway and a global translational remodelling in SCLC drug-tolerant persister-like cells. This prompts us to develop an eIF6-CD104/FAK proximity ligation assay applicable to clinical samples, showing its prognostic value for SCLC clinical outcomes. This study of eIF6’s moonlight function sheds light on its potential therapeutic interventions to mitigate treatment resistance in SCLC.
Plant hormones determine the differentiation of callus tissue during tissue culture of mature and immature Brachypodium distachyon embryos
Authors: Ouyang Dandan , Wei Jiagu , Ran Liping , Liu Peiyao , Xiong Fei , Yu Xurun
Published: May 2024

Brachypodium distachyon has emerged as a new model for the structural and functional genomics of temperate grasses. Somatic embryo culture serves as an effective method for the genetic transformation of B. distachyon. However, the role of regulatory genes in inducing somatic embryogenesis through endogenous hormone modulation in B. distachyon remains unexplored. This study investigated the endogenous hormone levels and transcriptome data of embryogenic calli (EC) derived from both mature and immature B. distachyon embryos. Our findings indicate that higher levels of IAA and GAs promote the formation of mature embryo-produced compact embryogenic calli (MEC), whereas higher tZR and lower ABA levels promote the development of immature embryo-produced compact embryogenic calli (IEC). The differential expression of genes involved in the biosynthesis and signal transduction of auxin (YUCCA,ALDH, AUX/IAA), trans-zeatin riboside (CKX), gibberellin (KAO, GA3ox), and abscisic acid (AAO3, SnRK2) influences the endogenous hormone concentrations in MEC and IEC of B. distachyon. Specifically, increased expression of AUX/IAA is linked to MEC formation. Thus, the differential expression of genes associated with the AUX, CK, GA, and ABA biosynthesis and signal transduction pathways may modulate endogenous hormone levels, steering the differentiation of MEC and IEC in B. distachyon.
Keywords Brachypodium distachyon·embryogenic calli· differentially expressed genes·endogenous hormone
Adaptive Hyperparameter Selection in Kernel-based Partition of Unity Methods by Global Optimization Techniques
Authors: Cavoretto Roberto , De Rossi Alessandra , Haider Adeeba , Sergeyev Yaroslav D.
Published: May 2024

In this article, we present a new numerical algorithm to detect the kernel shape parameter and the subdomain radius size within a partition of unity method for scattered data interpolation. Since an adaptive search of such hyperparameters is quite expensive from the computational point of view, we propose the use of a leave-one-out cross validation technique combined with univariate global optimization tools from the class of Lipschitz derivative-free method. Particularly, we consider efficient global optimization strategies characterized by optimistic and pessimistic improvements. The resulting algorithm allows us to improve the performance of the standard approach in terms of both accuracy and efficiency. Numerical results deriving from the study of some test cases and an application to real-world data support our analysis.
MSC Classification: 65D05 , 65D15 , 90C26 , 65K05
Temporal Interactions between Neural Proxies for Memory Recall, Negative Affect, and Emotion Regulation in Major Depression
Authors: Michel Christina , Schmidt Mike , Mann J. John , Herzog Sarah , Ochsner Kevin , Davachi Lila , Schneck Noam
Published: May 2024

Dysfunction in emotion regulation (ER) and autobiographical memory are components of major depressive disorder (MDD). However, little is known about how they mechanistically interact with mood disturbances in real time. Using machine learning-based neural signatures, we can quantify negative affect (NA), ER, and memory continuously to evaluate how these processes dynamically interact in MDD. Unmedicated individuals with MDD (N=45) and healthy volunteers (HV; N=38) completed a negative autobiographical memory functional magnetic resonance imaging task wherein they recalled, distanced from (an ER strategy), and immersed into memories. We used a negative affect signature (PINES) and an emotion regulation signature (ERS) to quantify moment-to-moment NA and ER. We then examined whether memory engagement, indexed by hippocampal activity, predicted subsequent change in PINES and ERS over time. During memory recall and immersion, greater hippocampal activity predicted increased PINES across groups. During distancing, greater hippocampal activity in HVs predicted increased ERS but not PINES. In MDD, greater hippocampal activity predicted increased PINES but not ERS. Findings suggest abnormalities in the real-time relationship between memory, NA, and ER in MDD. During distancing, as predicted, HVs showed an attenuation of the linkage between memory engagement and NA, and they had subsequent increases in ER following memory reactivation. In contrast, MDD was characterized by continued linkage between memory engagement and NA, without subsequent increases in ER. Deficits in engagement of ER and ineffective modulation of NA following negative memory recall may contribute to the mood disturbances in MDD and are potential targets for clinical intervention.
INAEME: Integral Neoantigen Analysis with Entirety of Mutational Events
Authors: Kovacevic Vladimir , Milicevic Ognjen , Raicevic Nevena Ilic , Kojicic Milica , Lazic Ana Mijalkovic , Skundric Nikola , DiGiovanna Jack
Published: May 2024

Neoantigens are peptides on the surface of cancer cells presented to the immune system. Multiple novel therapeutic approaches involve the administration of neoantigens to trigger immunity-induced tumor regression. Identification of neoantigens includes a personalized approach consisting of detailed analyses of the sequenced tumor tissue and its comparison with wild type to identify somatic mutations. Alternated peptides are translated from nucleotides around somatic mutations and their binding affinity and immunogenicity need to be further evaluated. Still, the entire bioinformatics analysis is very complex, and accurate prediction of the neoantigen candidates represents a true challenge. Here, we present the novel, integral bioinformatic analysis workflow for neoantigen discovery, denoted INAEME (Integral Neoantigen Analysis with Entirety of Mutational Events). The workflow performs integral processing of an individual's DNA tumor-normal and RNA tumor raw reads to output prioritized neoantigen candidates. Our evaluation analysis includes a wide scope of mutational events so far not considered in the existing solutions, including phasing of variants, influence of both somatic and germline variants, positions of all transcripts, neighboring variants, and frameshifts. The influence of each mutational event on the accuracy of predicted neoantigen candidates is tested across 300 TCGA samples from multiple cancer types. The obtained results have demonstrated the significance of considering the entirety of mutational events to obtain an accurate set of strong neoantigen candidates for cancer immunotherapy targets or vaccines. The adaption of the described methods in the bioinformatics analysis minimizes the existence of false positives which are only later discovered in a laboratory environment using expensive methods such as mass spectrometry or microscopy.
MRPL27 as a new prognostic biomarker involved in immune cell infiltration and hepatocellular carcinoma progression
Authors: Yang JiaYing , Lin Qinghua , Liu Xiayan , Chen Ke , Chen Xinyi , Han Junyong , Liao Zhijun
Published: May 2024

Mitochondrial ribosomal protein L27 (MRPL27) is a member of mitochondrial ribosomal proteins (MRPs). However, the biological function of MRPL27 in hepatocellular carcinoma (LIHC) is still unclear. Use UALCAN, TIMER, TISIDB, Kaplan Meier, and GEPIA database systems to analyze the expression, prognostic value, and relationship between MRPL27 and immune infiltration in LIHC. The expression and clinical significance of MRPL27 in LIHC patients were validated using tissue microarray. Conduct cell function experiments to detect the effects of overexpression and knockdown of MRPL27 on the proliferation, migration, and invasion of Huh7 cells. The tissue microarray results confirmed that MRPL27 expression is upregulated in LIHC, and high MRPL27 expression is associated with poorer prognosis. The expression of MRPL27 is significantly correlated with the infiltration levels of immune modulators, chemokines, and various immune cells. In addition, MRPL27 affects the proliferation, migration, and invasion of LIHC cells. These data indicate that MRPL27 is a new prognostic biomarker for LIHC and is associated with immune infiltration in LIHC.
PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [18F]TZ4877 in Nonhuman Primates
Authors: Gu Jiwei , Zheng Ming-Qiang , Holden Daniel , Fowles Krista , Qiu Lin , Felchner Zachary , Zhang Li , Ropchan Jim , Gropler Robert J , Carson Richard E , Tu Zhude , Huang Yiyun , Hillmer Ansel T
Published: May 2024

Purpose
The sphingosine-1-phosphate receptor-1 (S1PR1) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR1-specific radioligands with clinically suitable brain pharmcokinetic properties to complement existing radiotracers. This work evaluated a promising S1PR1 radiotracer, [18F]TZ4877, in nonhuman primates.
Procedures:
[18F]TZ4877 was produced via nucleophilic substitution of tosylate precursor with K[18F]/F− followed by deprotection. Brain PET imaging data were acquired with a Focus220 scanner in two Macaca mulatta (6, 13 years old) for 120–180 min following bolus injection of 118–163 MBq [18F]TZ4877, with arterial blood sampling and metabolite analysis to measure the parent input function and plasma free fraction (fP). Each animal was scanned at baseline, 15–18 min after 0.047–0.063 mg/kg of the S1PR1 inhibitor ponesimod, 33 min after 0.4–0.8 mg/kg of the S1PR1-specific compound TZ82112, and 167–195 min after 1 ng/kg of the immune stimulus endotoxin. Kinetic analysis with metabolite-corrected input function was performed to estimate the free fraction corrected total distribution volume (VT/fP). Whole-body dosimetry scans were acquired in 2 animals (1M, 1F) with a Biograph Vision PET/CT System, and absorbed radiation dose estimates were calculated with OLINDA.
Results
[18F]TZ4877 exhibited fast kinetics that were described by the reversible 2-tissue compartment model. Baseline [18F]TZ4877 fP was low (< 1%), and [18F]TZ4877 VT/fP values were 233–866 mL/cm3. TZ82112 dose-dependently reduced [18F]TZ4877 VT/fP, while ponesimod and endotoxin exhibited negligible effects on VT/fP, possibly due to scan timing relative to dosing. Dosimetry studies identified the critical organs of gallbladder (0.42 (M) and 0.31 (F) mSv/MBq) for anesthetized nonhuman primate.
Conclusions
[18F]TZ4877 exhibits reversible kinetic properties, but the low fP value limits quantification with this radiotracer. S1PR1 is a compelling PET imaging target, and these data support pursuing alternative F-18 labeled radiotracers for potential future human studies.
Mechanism of action of carbon nanoparticle verified in rice: Improved water use efficiency is the key
Authors: Kumar Aman , S Lekshmi Manasa , Kashyap Jyotiprabha , Mandal Sikha , Mishra Gayatri , Rath Jnanendra , Rout Gyana Ranjan , Panigrahi Kishore CS , Panigrahy Madhusmita
Published: May 2024

Mechanism of action and molecular basis of positive growth effects including yield increase due to carbon nanoparticle (CNP) treatment in rice plants is dissected here. CNP at 500–750 µg/mL were found to be the optimum dosages showing best seedling growth. CNP treatment resulted increase in stomata size, gaseous exchange and water use efficiency along with decrease in stomata frequency, relative humidity, internal CO2 concentration. CNP treatment exerted cold tolerance in seedlings and water stress tolerance in reproductive stage. CNP-coupled with water uptake was found to be endocytosis mediated, although CNP uptake was not affected by endocytosis inhibitor application in roots. Genomic analysis resulted major involvement of ABA pathway and stomata size and frequency genes in Arabidopsis and rice. Elevated endogenous ABA in rice seedlings and flag leaves along with increased expression of ABA biosynthetic genes in Arabidopsis and rice AtNCED3, AtNCED6, OsNCED1 confirmed increased ABA synthesis. Negative regulators of ABA pathway, OsSNRK2 down-regulation and up-regulation of stomagen (OsEPFL9) reconfirmed ABA’s involvement. CNP treatment resulted water stress tolerance by maintaining lower stomatal conductance, transpiration rate and higher relative water content. Increased ABA (OsSNRK1, OsSNRK2) and aquaporin (OsPIP2-5) genes’ expressions could explain the better water stress tolerance in rice plants treated with CNP. Altogether, due to thermomorphogenesis, down-regulation of Phytochrome B resulted altered the ABA pathway and stomatal distribution with size. These changes resulted improved water relation parameters and WUE showing improvement in yield. Detailed mechanism of action of CNP in abiotic stress tolerance can be exploited in in nano-agriculture.
The relationships between the expression of SPP1 and IL33 during the dedifferentiation of breast cancer associated adipocytes and the prognosis of breast cancer
Authors: Jiang Yuchan , Yang Chuang , Shi Han , Li Junfeng , Zhang Huan , Gao Yidan , Feng Xing , Tan Jinxiang
Published: May 2024

Purpose
We aimed to determine the biomarkers for breast cancer by studying the relationship between breast cancer and the dedifferentiation process of adipose tissue.
Methods
The public databases Gene Expression Omnibus (GEO) database, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases, the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database, the Kaplan-Meier Plotter database, the Human Protein Atlas (HPA) database and the TIMER 2.0 database were used to analyze. Immunohistochemical experiment was carried out to verify the expression of Secreted phosphoprotein 1 (SPP1) gene and the interleukin 33 (IL-33) gene in adipose tissue and breast cancer tissue respectively.
Results
Totally, 19 differentially expressed genes (DEGs) were identified and mainly enriched in the three signaling pathways. Compared with normal controls, SPP1 microRNA and IL33 microRNA were differently expressed (P < 0.05). And SPP1 and IL33 gene were related to the prognosis of estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER-2) negative breast cancer patients (P < 0.05). Immunohistochemical results showed that the positive expression rate of SPP1 and IL33 in breast cancer were higher than that in normal tissues; both associated with macrophages in breast cancer.
Conclusion
SPP1 and IL33 affect the prognosis of breast cancer during the dedifferentiation of breast cancer related adipocytes. The SPP1 and IL33 perhaps are potential biomarkers for breast cancer.
Insights into Immune Microenvironment and Therapeutic Targeting in Androgen-Associated Prostate Cancer Subtypes
Authors: Huang Liang , Xie Yu , Jiang Shusuan , Dai Tao , Xu Zhenzhou , Shan Hong
Published: May 2024

Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.
A comparison of regression models for static and dynamic prediction of a prognostic outcome during admission in electronic health care records
Authors: Gao Shan , Albu Elena , Putter Hein , Stijnen Pieter , Rademakers Frank , Cossey Veerle , Debaveye Yves , Janssens Christel , Calster Ben van , Wynants Laure
Published: May 2024

Background
Hospitals register information in the electronic health records (EHR) continuously until discharge or death. As such, there is no censoring for in-hospital outcomes. We aimed to compare different dynamic regression modeling approaches to predict central line-associated bloodstream infections (CLABSI) in EHR while accounting for competing events precluding CLABSI.
Methods
We analyzed data from 30,862 catheter episodes at University Hospitals Leuven from 2012 and 2013 to predict 7-day risk of CLABSI. Competing events are discharge and death. Static models at catheter onset included logistic, multinomial logistic, Cox, cause-specific hazard, and Fine-Gray regression. Dynamic models updated predictions daily up to 30 days after catheter onset (i.e. landmarks 0 to 30 days), and included landmark supermodel extensions of the static models, separate Fine-Gray models per landmark time, and regularized multi-task learning (RMTL). Model performance was assessed using 100 random 2:1 train-test splits.
Results
The Cox model performed worst of all static models in terms of area under the receiver operating characteristic curve (AUC) and calibration. Dynamic landmark supermodels reached peak AUCs between 0.741–0.747 at landmark 5. The Cox landmark supermodel had the worst AUCs (≤ 0.731) and calibration up to landmark 7. Separate Fine-Gray models per landmark performed worst for later landmarks, when the number of patients at risk was low.
Conclusions
Categorical and time-to-event approaches had similar performance in the static and dynamic settings, except Cox models. Ignoring competing risks caused problems for risk prediction in the time-to-event framework (Cox), but not in the categorical framework (logistic regression).
Acid-Induced In Situ Phase Separation and Percolation for Constructing Bi-Continuous Phase Hydrogel Electrodes with High Conductivity and Robust Mechanical Properties
Authors: Bai Shuo , Han Qingquan , Gao Xigang , Zhang Chao , Tian Yajie , Liang Sen , Li Xin , Jing Yafeng , Zhang Milin , Wang Anhe
Published: May 2024

Conductive polymer hydrogels have emerged as promising materials for wearable bioelectronics due to their inherent biocompatibility and stability in physiological conditions. However, achieving hydrogel electrodes with excellent conductivity and mechanical properties is challenging due to the inherent contradiction between the hydrophobicity of conductive materials and the hydrophilicity of hydrogels. Herein, we introduce a hydrogel integrating PVA, PVP and PEDOT:PSS, and propose a single-step acid-induced strategy that not only facilitates gelation but also ensures in situ phase separation of PEDOT:PSS under mild conditions, resulting in a unique bi-continuous phase structure combining excellent electrical and mechanical properties. Upon reaching the percolation threshold at 4.8 mg mL-1 PEDOT:PSS, the electrical conductivity surges to 906 mS cm-1. The hydrogel also exhibits unprecedented mechanical resilience, with a fracture strain of 1103%, significantly surpassing previous reports of PEDOT:PSS-based conductive materials. This stretchability, coupled with low mechanical hysteresis (dissipation energy less than 1.2 kJ m-3) and a resilience rate of approximately 95%, highlights its superior mechanical integrity and fatigue resistance. The hydrogel electrodes demonstrate substantially lower noise power (4.9 μV²) compared to commercial gel electrodes (1541.8 μV²) and Ag/AgCl electrodes (>34.4 μV²). The hydrogel sets a new benchmark for the performance of conductive hydrogels in wearable bioelectronics, offering exceptional mechanical properties and superior electrical functionality for efficient and reliable monitoring of biological signals.
Individual identification and forensic applications with microsatellites in a non-invasive monitoring of Antilophia bokermanni
Authors: Oliveira Alison Honorio , Andrade Amanda Oliveira , Santos Marcos Aurelio Figueiredo , Alcântara Ana Cleide , Ribeiro Samuel Cardozo , Silva Maria Arlene Pessoa da , Coutinho Henrique Douglas Melo
Published: May 2024

The applicability of a panel of microsatellites in studies focused on conservation can be decisive in obtaining information on endangered species, such as the Soldadinho-do-Araripe. In the present work, it was tested a set of 12 microsatellite loci in order to evaluate the potential of carrying out the individual identification process and the establishment of family relationships necessary for future conservation monitoring of the species. This set of microsatellites proved capable of carrying out the potential identification of exclusive genotypes, in addition to revealing the family pedigree between individuals, determining possible parents/offspring, full siblings and half-siblings. This research will provide support in obtaining predictions of one or more possible sites (springs that have family groups) that can serve as a source of rare alleles and from that translocation programs are implemented and consequently ecological stations function as in situ germplasm banks, enabling the current and future monitoring of this species whose maintenance and conservation will help as a model in the preservation of biodiversity in Chapada do Araripe, Ceará, Brazil.
Daily life mobility detects frailty, falls, and functioning in ADT-treated prostate cancer survivors
Authors: Tibbitts Deanne C. , Mancini Martina , Stoyles Sydnee , Dieckmann Nathan F. , Graff Julie N. , El-Gohary Mahmoud , Horak Fay B. , Winters-Stone Kerri M.
Published: May 2024

Background
Androgen deprivation therapy (ADT) increases the risk of frailty, falls, and, poor physical functioning in prostate cancer survivors. Detection of frailty is limited to self-report instruments and performance measures, so unbiased tools are needed. We investigated relationships between an unbiased measure – daily life mobility – and ADT history, frailty, falls, and functioning in ADT-treated prostate cancer survivors.
Methods
ADT-treated prostate cancer survivors (N=99) were recruited from an exercise clinical trial, an academic medical center, and the community. Participants completed performance measures and surveys to assess frailty, fall history, and physical functioning, then wore instrumented socks to continuously monitor daily life mobility. We performed a principal component analysis on daily life mobility metrics and used regression analyses to investigate relationships between domains of daily life mobility and frailty, fall history, and physical functioning.
Results
Daily life mobility metrics clustered into four domains: Gait Pace, Rhythm, Activity, and Balance. Worse scores on Rhythm and Activity were associated with increased odds of frailty (OR 1.59, 95% CI: 1.04, 2.49 and OR 1.81, 95% CI: 1.19, 2.83, respectively). A worse score on Rhythm was associated with increased odds of ≥1 falls in the previous year (OR 1.60, 95% CI: 1.05, 2.47). Worse scores on Gait Pace, Rhythm, and Activity were associated with worse physical functioning. Mobility metrics were similar between current and past users of ADT.
Conclusions
Continuous passive monitoring of daily life mobility may identify prostate cancer survivors who have or are developing risk for frailty, falls, and declines in physical functioning.
Alkane gene expression and its increased production in recombinant cyanobacteria
Authors: Nagao Misato , Ozaki Takato , Fukuda Hirofumi , Kanesaki Yu , Asayama Munehiko
Published: May 2024

Background: In cyanobacteria, the mechanism of the biosynthetic pathway of alkanes, which are useful materials for transportation biofuels in automobiles and airplanes, is being elucidated by genetic analytical methods. However, to date, no study has consistently analysed the transcription of alkane genes, molecular structure of mRNA, production of alkanes depending on the culture medium, catalytic activity of enzymes as indicated by the increased production of alkanes by the recombinant strain, or alkane accumulation in cells.
Results: Transcription start point (TSP) of alkane genes ado and aar in the representative cyanobacteria Synechocystis sp. PCC 6803 and Limnothrix sp. SK1-2-1 strains producing C17H36 and C15H32, respectively, were determined at -88/-72 (6803_ado/aar) and -70/-20 (SK1-2-1_ado/aar). From the TSPs, consensus promoter sequences were identified, and the transcripts possessed unique stem and loop (S&L) structure at 5’- and 3’-UTR regions, which can regulate mRNA stability, translation initiation, and transcription termination. Alkane gene transcript levels were higher in nitrogen- and phosphorus-depleted BG11 media; however, higher amount of alkanes was produced in BG11 medium because of the reduced biomass. Transconjugants in which 6803_ado/aar or SK1-2-1_ado/aar were cloned into an algal expression vector and inserted into PCC 6803 strain produced approximately 1.6- to 2.2-times more C17 alkanes (C17H36) than that of wild-type strain in both cases. When alkane hyperaccumulator strains were cultured in BG11 or BG11-N/-P/-S medium, TEM observation showed clearly different cell shapes and accumulated products under each condition, but no significant accumulation, such as oil drops, was observed.
Conclusion: New transcription start sites and predicted promoter sequences were identified, and unique S&L structures were found in 5'-UTR and 3'-UTR regions of each transcript, indicating mRNA stability and efficiency of translation initiation or termination. Although nutrient-depleted media are effective for alkane gene mRNA accumulation, it is clear that alkane accumulation per unit medium volume is higher when BG11 medium is used, given the reduced biomass. Experiments using recombinant strains for alkane production have shown that not only the enzymatic activity of ADO/AAR but also the intracellular production level of fatty-acyl ACP substrate may be important for mass production of alkanes with the desired carbon chain lengths.
MPicker: Visualizing and Picking Membrane Proteins for Cryo-Electron Tomography
Authors: Li Xueming , Yan Xiaofeng , Li Shudong , Huang Weilin , Wang Hao , Zhao Tianfang , Huang Mingtao , Zhou Niyun , Shen Yuan
Published: May 2024

Advancements in cryo-electron tomography (cryoET) allow the structure of macromolecules to be determined in situ, which is crucial for studying membrane protein structures and their interactions in the cellular environment. However, membranes are often highly curved and have a strong contrast in cryoET tomograms, which masks the signals from membrane proteins. These factors pose difficulties in observing and revealing the structures of membrane proteins in situ. Here, we report a membrane-flattening method and the corresponding software, MPicker, designed for the visualization, localization, and orientation determination of membrane proteins in cryoET tomograms. This method improves the visualization of proteins on and around membranes by generating a flattened tomogram that eliminates membrane curvature and reduces the spatial complexity of membrane protein analysis. In MPicker, we integrated approaches for automated particle picking and coarse alignment of membrane proteins for sub-tomogram averaging. MPicker was tested on tomograms of various cells to evaluate the method for visualizing, picking, and analyzing membrane proteins.
Combined duplicate origin and early bifurcated middle cerebral artery diagnosed by magnetic resonance angiography
Authors: Uchino Akira , Kobayashi Satoshi
Published: May 2024

Purpose
To describe a case of combined duplicate origin and early bifurcated middle cerebral artery (MCA) incidentally diagnosed using magnetic resonance (MR) angiography.
Methods
A 51-year-old woman with an unruptured left MCA aneurysm underwent cranial MR angiography with a 3-Tesla scanner for presurgical evaluation. MR angiography was performed using a standard 3-dimensional time-of-flight technique.
Results
An unruptured left MCA aneurysm at the M1-M2 junction was identified. The maximum aneurysm diameter was 9 mm. Two almost equally sized right MCAs arose from the terminal segment of the right internal carotid artery. These two channels soon anastomosed, and the temporal branch arose from the inferior channel. The aneurysm was successfully treated with coil embolization.
Conclusion
We herein report a case of a combined duplicate origin and early bifurcated MCA. This variation can also be regarded as anastomosis between the main MCA and the duplicated MCA. This variation has been previously reported as segmental duplication of the MCA. This is the third case of this rare MCA variation reported in the relevant English-language literature. The term “segmental duplication” may be confused with duplicate origin of the MCA, in which only one artery is located distal to the fusion.