bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Advances in Bispecific T Cell–Engaging Therapies
Authors: Ansah Emmanuel Owusu , Nyarko Bernard Ansong
Published: January 2024

The emergence of bispecific antibodies has transformed cancer immunotherapy, highlighting increased clinical efficacy, especially in hematological malignancies. These innovative molecules uniquely target two distinct tumor antigens or separate epitopes simultaneously, demonstrating potent antitumor activity across various cancers. Despite their promise, challenges like rapid drug clearance, off-target effects, and cytokine release syndrome hinder their widespread therapeutic application. Recent engineering advancements in bispecific antibody systems aim to overcome these challenges, broadening therapeutic coverage. This review offers insights into the latest clinical and preclinical progress in bispecific immunotherapy, outlining key challenges faced by the technique, and exploring emerging strategies to address these obstacles.
Subtype Transdifferenziation in Human Cancer: The Power of Tissue Plasticity in Tumor Progression
Authors: Fedele Monica , Cerchia Laura , Battista Sabrina
Published: January 2024

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.
FXR agonism with bile acid mimetic reduces pre-clinical triple-negative breast cancer burden
Authors: Joseph Sydney Clarice , Eugin Simon Samson , Bohm Margaret Sue , Kim Minjeong , Pye Madeline E , Simmons Boston William , Graves Dillon Garen , Thomas-Gooch Stacey Marchelle , Tanveer Ubaid A , Holt Jeremiah Ray , Ponnusamy Suriyan , Sipe Laura M , Hayes D. Neil , Cook Katherine Loree , Narayanan Ramesh , Pierre Joseph F , Makowski Liza
Published: January 2024

Obesity is one of the most prevalent chronic diseases and has become a global epidemic. Obesity leads to a greater risk of breast cancer (BC), metastases, recurrence, and decreased survival. For sustained weight loss, bariatric surgery is effective as a long-term solution. Bariatric surgery is associated with improved outcomes of several cancers including BC, although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Indeed, patients with greater expression of the bile acid receptor FXR displayed improved survival in specific BC subtypes. Patients with tumors that are estrogen receptor negative (ER-) displayed significantly elevated survival with higher FXR (NR1H4) expression compared to lower expression. FXR is a nuclear hormone receptor activated by bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would display anticancer effects. Indeed, FXR agonism by the bile acid mimetic known commercially as OCALIVA (“OCA”), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor (GPBAR1, TGR5) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. Findings suggest that FXR is a tumor suppressor gene with high potential for personalized therapeutic strategies for individuals with BC.
TGF- β Signaling Pathways in the Development of Diabetic Retinopathy
Authors: Callan Andrew , Jha Sonal , Valdez Laura , Baldado Lois , Tsin Andrew
Published: January 2024

Diabetic retinopathy (DR), a prevalent complication of diabetes mellitus affecting a significant portion of the global population, has long been viewed primarily as a microvascular disorder. However, emerging evidence suggests that it should be redefined as a neurovascular disease with multifaceted pathogenesis rooted in oxidative stress and advanced glycation end products. The transforming growth factor-β (TGF-β) signaling family has emerged as a major contributor to DR pathogenesis due to its pivotal role in retinal vascular homeostasis, endothelial cell barrier function, and pericyte differentiation. However, the precise roles of TGF-β signaling in DR remain incompletely understood, with conflicting reports on its impact in different stages of the disease. Additionally, the BMP subfamily within the TGF-β superfamily introduces further complexity, with BMPs exhibiting both pro- and anti-angiogenic properties. Furthermore, TGF-β signaling extends beyond the vascular realm, encompassing immune regulation, neuronal survival, and maintenance. The intricate interactions between TGF-β and reactive oxygen species (ROS), non-coding RNAs, and inflammatory mediators have been implicated in the pathogenesis of DR. This review delves into the complex web of signaling pathways orchestrated by the TGF-β superfamily and their involvement in DR. A comprehensive understanding of these pathways may hold the key to developing targeted therapies to halt or mitigate the progression of DR and its devastating consequences.
Back to the Future of Metabolism – Advances in the Discovery and Characterization of Unknown Biocatalytic Functions and Pathways
Authors: Wohlgemuth Roland
Published: January 2024

The architecture, organization and functioning of biocatalytic reaction networks, which are coded in the cell specific genome and which work together in the small space of biological cells, are a fascinating feature of life evolved over more than 3 billion years. The knowledge about the diversity of biocatalytic functions and metabolic pathways sustaining life on our planet is highly important, especially as the currently occurring loss of biodiversity is considered a planetary boundary which is at high risk, and knowledge about the life of current biological organisms should be gained before they become extinct. In addition to the well-known enzymatic reactions involved in biochemical pathways, the enzyme universe offers numerous opportunities for discovering novel functions and pathways. Maintaining thousands of molecules and reactions functioning properly within biological cells, which may be exposed to various kinds of external hazards, environmental stress, enzymatic side reactions or non-enzymatic chemical reactions, is key for keeping cellular life healthy. This review aims at outlining advances in assigning enzyme functions to protein sequences and the discovery of novel biocatalytic functions and pathways.
Recent Advances Towards the Understanding of Secondary Acute Myeloid Leukemia Progression
Authors: Auerbach Scott , Puka Beana , Golla Upendarrao , Chachoua Ilyas
Published: January 2024

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.
Electrodeposition of Silicon Fibers from KI–KF–KCl–K2SiF6 Melt and their Electrochemical Performance During Lithiation/Delithiation
Authors: Leonova Anastasia , Leonova Natalia , Minchenko Lyudmila , Suzdaltsev Andrey
Published: January 2024

The possibility of using Si-based anodes in lithium-ion batteries is actively investigated due to the increased lithium capacity of silicon. The paper reports the preparation of submicron silicon fibers on glassy carbon in the KI–KF–KCl–K2SiF6 melt at 720°C. For this purpose, the parameters of silicon electrodeposition in the form of fibers were determined by cyclic voltammetry, and ex-perimental samples of ordered silicon fibers with an average diameter from 0.1 to 0.3 μm were obtained under galvanostatic electrolysis conditions. Using the obtained silicon fibers, anode half-cells of lithium-ion battery was fabricated, and its electrochemical performance under mul-tiple lithiation and delithiation was studied. By means of voltametric studies, it is observed that charging and discharging of the anode based on the obtained silicon fibers occurs at potentials from 0.2 to 0.05 V and from 0.2 to 0.5 V, respectively. A change in discharge capacity from 520 to 200 mAh g-1 during the first 50 charge/discharge cycles at a charge current of 0.1C and a Coulomb ef-ficiency of 98-100% was shown. The possibility of charging silicon-based anode samples at charging currents up to 2C was also noted; the discharge capacity ranged from 25 to 250 mAh g-1.
Exploring the In Vitro Antibacterial Potential of Specific Probiotic Strains Against Oral Pathogens
Authors: Squarzanti Diletta Francesca , Dell'Atti Federica , Scalia Alessandro Calogero , Najmi Ziba , Cochis Andrea , Malfa Patrizia
Published: January 2024

The microbiota in the oral cavity has a strict connection to its host. Its unbalance may determine oral diseases and can also have an impact on the systemic health. Probiotic strains may help in the restoration of a balanced condition. For this purpose, we screened the antibacterial and antiadhesive activities of many viable probiotic strains (Lactobacillus acidophilus PBS066, Lactobacillus crispatus LCR030, Lactobacillus gasseri LG050, Lactiplantibacillus plantarum PBS067, Limosilactobacillus reuteri PBS072, Lacticaseibacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050, Lacticaseibacillus paracasei LPC 1101, L. paracasei LPC 1082, and L. paracasei LPC 1114) against two main oral pathogens, Streptococcus mutans and Aggregatibacter actinomycetemcomitans, involved in dental caries and periodontal disease development and progression. Our results, obtained through agar overlay assay, plate count method, and scanning electron microscope imaging, indicate that the tested probiotics prevent the growth and adhesion of oral pathogens in a strain-specific manner, improving oral health. L. plantarum PBS067, L. rhamnosus LRH020, L. paracasei LPC 1101, L. paracasei LPC 1082, and L. paracasei LPC 1114 performed in a significant way against both pathogens in all the tests used. They can be considered as an effective adjuvant to guarantee oral and systemic well-being.
Strengthening Pathogen and Antimicrobial Resistance Surveillance by Environmental Monitoring in Sub-Saharan Africa: A Stakeholder Survey
Authors: Tiwari Ananda , Miller Taru , Baraka Vito , Tahita Marc , Maketa Vivi , Kabore Berenger , Kingpriest Paul , Mitashi Patrick , Lyimo Erick , Sebukoto Hillary , Pitkänen Tarja
Published: January 2024

Background: Waterborne diseases pose a significant global public health threat, compelling enhanced comprehensive surveillance. This study investigates the current infectious disease and antimicrobial resistance (AMR) surveillance systems, including wastewater and environmental surveillance (WES), in three sub-Saharan African countries: Tanzania, Burkina Faso, and the Democratic Republic of the Congo (DRC). The three countries have their specificities regarding wastewater networks and logistic systems. So, emphasizing the need to strengthen existing disease surveillance, the paper advocates for incorporating WES systems specifically designed for countries' context to monitor waterborne and re-emerging pathogens, as well as AMR.Methods: National workshops were conducted to assess the current clinical and environmental surveillance systems and identify priority pathogens for new environmental monitoring. Data were collected through surveys from experts in academia, research, policy, and healthcare. Results: Prioritized pathogens for WES include waterborne (poliovirus, Salmonella Typhi, Vibrio cholerae), respiratory (influenza A&B, SARS-CoV-2), other (Measles and Rubella, Mycobacterium tuberculosis). Recommended AMR pathogens include drug-resistant Mycobacterium tuberculosis, Salmonella spp., methicillin-resistant Staphylococcus aureus, and extended-spectrum beta-lactamase and carbapenemase-producing E. coli. Tanzania, Burkina Faso, and the DRC employ DHSI2-based centralized electronic systems for clinical data collection, complemented by Excel and paper-based registries. The WES approach is commonly employed for monitoring poliovirus and rarely for AMR and other pathogens. Discussion and conclusions: WES is a valuable tool for early detection of locally circulating human-derived pathogens, aiding in outbreak detection, data-driven epidemic response, and prevention. The availability of WES results underscores the importance of effective sanitation for safeguarding human, animal, and environmental health. WES is a pivotal tool for integrated risk management, preventing waterborne outbreaks, protecting drinking water sources, and ultimately gaining various UN Sustainable Development Goals. The study highlights the importance of customized WES systems in line with each country's context, emphasizing localized approaches for effective monitoring of waterborne pathogens and AMR.
THE INFLUENCE OF OFFICIAL TIKTOK HANASUI VIDEO CONTENT ON BRAND AWARENESS AND CONSUMER BUYING INTEREST IN SOLO RAYA
Authors: Alfrico Windu Kurniansyah  , Anggi Wulandari  , Diva Yuni Harminingsih  , Faizal Nur Rachman  , Pradipta Eva Kusuma
Published: January 2024

TikTok is considered as one of the means to promote products. This phenomenon provides an opportunity for beauty companies to utilize TikTok as a tool to increase brand awareness and consumer buying interest. This study aims to examine the significance of the influence of Hanasui's official Tiktok content on brand awareness and purchase intention of Hanasui products. This research adopts a descriptive quantitative approach using descriptive quantitative research methods. The minimum sample size taken was 42 respondents by applying non-probability sampling through purposive sampling technique. Data collection was carried out through questionnaire distribution, and data analysis was carried out using simple linear regression analysis. The results showed a positive and significant effect of TikTok Hanasui Official video content on the variables of brand awareness and purchase intention of Hanasui products. These findings indicate that utilizing the TikTok platform in marketing strategies can help companies increase brand awareness and product purchase intention. Beauty companies can consider using Tik Tok as one of the tools to increase the marketing effectiveness of their products. Hanasui Official's Tiktok video content has a positive influence on brand awareness and purchase intention, companies can design more focused and efficient marketing strategies.
Etika dalam Mitos dan Legenda Islam: Menggali Kearifan Tradisional
Authors: Ningtias Annisa , Fahrudin Fahrudin
Published: January 2024

Artikel ini bertujuan untuk menggali aspek etika dalam mitos dan legenda Islam sebagai reservoir nilai-nilai moral dan etika . Penelitian ini menggunakan pendekatan interdisipliner, menggabungkan studi sastra, agama, dan etika untuk memahami kedalaman relevansi kearifan tradisional Indonesia yang terkandung dalam mitos dan legenda Islam. Dengan menganalisis narasi-narasi kuno dan cerita-cerita epik dalam warisan Islam, studi ini memaparkan bahwa etika bukan hanya sebuah konsep abstrak, tetapi juga sebuah panduan hidup yang tercermin dalam cerita-cerita kuno. Hasil penelitian ini mengungkapkan kompleksitas etika dalam berbagai konteks mitos dan legenda Islam, yang mencakup nilai-nilai seperti kejujuran, kebijaksanaan, keberanian, dan kasih sayang. Analisis mendalam terhadap kisah-kisah seperti "Kisah Ali Baba" dan "Kisah Nabi Sulaiman" menyoroti bagaimana nilai-nilai ini terjalin dalam narasi-narasi tersebut dan memberikan arahan etis bagi pembaca. Studi ini merangsang pemikiran tentang bagaimana masyarakat Islam dapat menggali kekayaan etika dalam warisan budaya mereka untuk memandu tindakan dan keputusan mereka dalam kehidupan sehari-hari. Kesimpulannya, artikel ini menyoroti pentingnya mengintegrasikan kearifan tradisional dalam kajian etika kontemporer
A modular framework for FAIR shallow landslide susceptibility mapping based on machine learning
Authors: Edrich Ann-Kathrin , Yildiz Anil , Roscher Ribana , Bast Alexander , Graf Frank , Kowalski Julia
Published: January 2024

Machine learning has grown in popularity in the past few years for susceptibility and hazard mapping tasks. Necessary steps for the generation of a susceptibility or hazard map are repeatedly implemented in new studies. We present a Random Forest classifier-based landslide susceptibility and hazard mapping framework to facilitate future mapping studies using machine learning. The framework, as a piece of software, follows the FAIR paradigm, and hence is set up as a transparent, reproducible and modularly extensible workflow. It contains pre-implemented steps from conceptualisation to map generation, such as the generation of input datasets. The framework can be applied to different areas of interest using different environmental features and is also flexible in terms of the desired scale and resolution of the final map. To demonstrate the functionality and validity of the framework, and to explore the challenges and limitations of Random Forest-based susceptibility and hazard mapping, we apply the framework to a test case. This test case conveys the influence of the training dataset on the generated susceptibility maps in terms of feature combination, influence of non-landslide instances and representativeness of the training data with respect to the area of interest. A comparison of the test case results with the literature shows that the framework works reliably. Furthermore, the results obtained in this study complement the findings of previous studies that demonstrate the sensitivity of the training process to the training data, particularly in terms of its representativeness.
Controlling metabolic stability of food microbiome for stable indigenous liquor fermentation
Authors: Santos Vitor Martins dos , Tan Yuwei , Zhu Yang , Wijffels René , Zhang Hongxia , Scott William , Xu Yan
Published: January 2024

Steering microbial metabolic stability in fermentation is a recurrent goal for developing sustainable and robust microbial food production systems. Indigenous liquor fermentation typically relies on complex microbiome metabolism that makes it difficult to steer fermentation towards consistent high-quality products. Here, we designed a three-step experiment to identify and understand instability factors and to steer fermentation stability accordingly. We found that the metabolic stability of the microbiome fluctuates due to a combination of community assembly responses to fermentation parameters, dynamic benefit allocation between yeasts and Lactobacilli, and functional redundancy of metabolic networks associated with biodiversity. Short-term metabolic stability needs stable allocation of microbial benefits, whereas long-term requires proper functional redundancy. Rationally setting initial parameters and the microbial inoculation ratio is a practical way to optimize metabolic stability for stable solid-state indigenous fermentation. Our study provides insights into the underlying interactions and shows the feasibility of enhancing metabolic functional stability by setting appropriate initial conditions in dynamic microbial ecosystems.
A nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
Authors: Walter Nils , Chauvier Adrien , Dandpat Shiba , Romero Rosa
Published: January 2024

Widespread manganese-sensing transcriptional riboswitches effect the dependable gene regulation needed for bacterial manganese homeostasis in changing environments. Riboswitches – like most structured RNAs – are believed to fold co-transcriptionally, subject to both ligand binding and transcription events; yet how these processes are orchestrated for robust regulation is poorly understood. Through a combination of single molecule and bulk approaches, we discovered how a single Mn2+ ion and the transcribing RNA polymerase (RNAP), paused immediately downstream by a DNA template sequence, are coordinated by the bridging switch helix P1.1 in the paradigmatic Lactococcus lactis riboswitch. This coordination achieves a heretofore-overlooked semi-docked global conformation of the nascent RNA, P1.1 base pair stabilization, transcription factor NusA ejection, and RNAP pause extension, thereby enforcing transcription readthrough. Our work demonstrates how a central, adaptable RNA helix functions analogous to a molecular fulcrum of a first-class lever system to integrate disparate signals for finely balanced gene expression control.
Modal Analysis and Frequency Matching Study of Subway Bogie Architecture under Environmental Excitation
Authors: Shen Longjiang , He Shizhong
Published: January 2024

A wealth of practical cases indicates that the fatigue failure of subway bogies primarily stems from the modal resonance of the structure. If the modal characteristics of the entire vehicle, including equipment and bogies, are mismatched, rail vehicles may experience abnormal vibrations and noise. Therefore, it is imperative to conduct modal analysis and mistuning design for subway vehicle bogies to ensure smooth operation, reduce structural vibrations and noise, and enhance vehicle safety and ride comfort. Modal identification methods under the environmental excitations during vehicle operation were employed to identify the modal parameters of the bogie structure before and after wheel turning and under different load conditions. According to the test results, wheel turning has minimal impact on the modal parameters of the structure, but with an increase in load, the modal frequencies of each order generally increase. This is associated with boundary constraint states, such as the increased stiffness of the bogie air spring with an increase in vehicle load. By comparing the test results with simulation analysis results of the bogie structure under free and constrained states, it is evident that simulating realistic boundary constraint conditions is crucial to ensure the accuracy of the finite element model. Based on frequency isolation criteria and vibration isolation theory, a frequency planning basis for the bogie structure was established. The study found that as the vehicle load increases, changes in the boundary conditions of the bogie affecting the elastic modal frequencies of the structure may have a certain impact on mistuning design, and may even better comply with the requirements of frequency management formulas. This provides a new direction for subsequent scholars researching modal mistuning design.
Gd-Doped Ceria with Extraordinary Oxygen-Ion Conductivity for Low Temperature Solid Oxide Fuel Cells
Authors: Vinchhi Prerna , Ray Abhijit , Mallik Kaushik , Pati Ranjan
Published: January 2024

Doped ceria has been extensively explored as an efficient electrolyte material for intermediate to low temperature solid oxide fuel cell. Among other ceria electrolytes, gadolinia doped ceria (GDC) is one of the most extensively studied electrolyte materials for low temperature SOFC applications. Here, co-precipitation method is employed to synthesize GDC composites with stoichiometric ratio of GdxCe1−xO2−δ (with 0\(\le\)x \(\le 0.\)20). In this process, the molecular water of the precursors has been utilized during the co-precipitation to avoid possible agglomeration caused by hydrogen bonding. The cubic phase formation was examined using X-ray diffraction (XRD) and Raman profile ascribing absence of other phases. The granularity of the sample was observed using field emission scanning electron microscopy (FESEM) with elemental mapping by EDS. The electrochemical behavior was investigated using electrochemical impedance spectroscopy (EIS), which was taken between the temperature ranges of 350–700°C. It is observed from the EIS study that ceria doped with 15 mol % Gd3+ (Gd0.15Ce0.85O2−δ) is having highest grain boundary ionic conductivity of about 0.104 S cm−1 at 700°C with an activation energy of 0.81 eV. This work demonstrates the correlation between oxygen vacancy generation and the enhancement of ionic conductivity with Gd3+ doping in ceria.
RETRACTED: Foliar Application of Ortho Silicic Acid (Silixol) Elicits Distinctive Physio- biochemical Responses in Sugarcane Under Water Deficit Stress
Authors: Hegde Vinay , Rathod Tarasingh , Chanumolu H G K , Gurumurthy S , Ghorade R B , Rane Jagadish
Published: January 2024

The authors have requested that this preprint be removed from Research Square.
Dynamic environment but no temperature change since the late Paleogene at Lühe Basin (Yunnan, China)
Authors: Witkowski Caitlyn , Lauretano Vittoria , Farnsworth Alexander , Li Shufeng , Li Shihi , Mayser Jan Peter , Naafs David , Spicer Robert , Su Tao , Tang He , Zhou Zhekun , Valdes Paul , Pancost Richard
Published: January 2024

The Eocene-Oligocene transition (EOT; ~34 million years ago) marks a critical shift from a greenhouse to an icehouse climate. Whereas temperatures derived from marine records show a consensus ~ 4°C cooling worldwide, there is an emerging picture that the terrestrial realm experienced a heterogenous response to rapid climate change. Here, we reconstruct an 8-million-year terrestrial temperature record across the EOT at a tectonically unresolved location at the margins of the Tibetan Plateau, Lühe Basin (Yunnan, China). Our multi-proxy organic geochemistry approach, complemented by sedimentological interpretations, shows that Lühe Basin was a dynamic fluvial environment that maintained relatively stable average temperatures from ~ 35 − 27 million years ago. These palaeotemperatures match our model-based estimates, as well as palaeobotany-based estimates at a nearby site; these stable palaeotemperature trends differ from the global marine cooling, supporting a heterogenous response of terrestrial sections. Furthermore, these palaeotemperature estimates match present-day values at this location, suggesting that this area has not undergone significant temperature change – and possibly no significant uplift – since the late Paleogene.
Investigation on the width-to-depth ratio effect on turbulent flows in a sharp meandering channel with periodic boundaries using Large Eddy Simulations
Authors: Zhang Bingchang , Xu Dong , Ji Chunning , Ran Qihua
Published: January 2024

As one of the most common river patterns in nature, meandering river has very complex flow structures in its curved channel bends, including secondary flow structure and primary flow velocity redistributions. To date, most of the studies have been carried out on the complex flow structures of a single channel bend with unavoidable influence, while the turbulent flow structures in periodic sharp meandering channels require further investigations. In this paper, Large Eddy Simulations (LES) are employed to reveal the flow structures of periodic sharp sine-generated bends with different width-to-depth ratios and dimensionless curvature radiuses. The results highlight the determining effects of width-to-depth ratio on recirculation zone’s size, the recirculation zone’s size is generally larger in Sine-Generated-Curve (SGC) Channel with large width-to-depth ratio, its size reaches maximum between the zero-curvature section and the apex section. The IBC (Inner bank cell) only forms in a small-sinuosity SGC channel with a small width-to-depth ratio, for SGC channel with large width-to-depth ratio, only one circulation cell is observed near the inner bank. The turbulent kinetic energy (TKE) is mainly influenced by width-to-depth ratio and dimensionless curvature radius.
Transcriptomic and metabolomic profiling provide insight into the role of sugars and hormones in leaf senescence of Pinellia ternata
Authors: Chen Jialei , Li Xiwen , Feng xue , Wang Jialu , Pei Yifei , Liu li , Liu ziyi
Published: January 2024

Pinellia ternata, an environmentally sensitive medicinal plant, undergoes leaf senescence twice a year, affecting its development and yield. However, the underlying mechanism of this phenomenon is still largely unexplored. In this study, a typical senescent population model was constructed, and an integrated analysis of transcriptomic and metabolomic profiles of P. ternatawas conducted using obviously different leaf senescence phenotypes in this model. The result showed that two key modules associated with leaf senescence based on weighted correlation network analysis (WGCNA) were key components for leaf senescence. Further analysis revealed that genes in these two modules were mainly enriched in sugar and hormone signaling pathways, respectively. A network of unigenes and metabolisms related to the obtained two pathways revealed that D-arabitol and 2MeScZR played key roles in leaf senescence. Additionally, a total of 130 hub genes were discovered in this network, and they were categorized into three classes based on connectivity. A total of 34 hub genes and 13 metabolites were further analyzed through a pathway map, the potential crosstalk between sugar and hormone metabolisms might be an underlying reason of leaf senescence inP. ternata. These findings address the knowledge gap regarding leaf senescence in P. ternata, providing candidate germplasms for molecular breeding and laying theoretical basis for the realization of finely regulated cultivation in future.
Health mediation does not reduce the readmission rate of frequent users of emergency departments living in precarious conditions: what lessons can be learned from this randomised controlled trial?
Authors: Rotily Michel , Persico Nicolas , Lamouroux Aurore , Rojas-Vergara Ana Cristina , Auquier Pascal , Apostolidis Themistoklis , Odena Sophie , Chischportich Celia , Loundou Anderson , Boucekine Mohamed
Published: January 2024

Background: Severe overcrowding of emergency departments (EDs) affects the quality of healthcare. One factor of overcrowding is precariousness, but it has rarely been considered a key factor in designing interventions to improve ED care. Health mediation (HM) aims to facilitate access to rights, prevention, and care for the most vulnerable persons and to raise awareness among healthcare providers about obstacles in accessing healthcare. The primary aim of this study was to determine whether HM intervention for frequent users of EDs (FUED) living in precarious conditions could reduce the readmission rate at 90 days.
Methods: Between February 2019 and May 2022, we enrolled and interviewed 726 FUED in four EDs of southeastern France in this randomised controlled trial. The HM intervention started in the ED and lasted 90 days. The outcome was measured in the ED information systems. Statistical methods included an intention-to-treat analysis and a per-protocol analysis. Comparisons were adjusted for gender, age, ED, and health mediator.
Results: 46% of patients reported attending the ED because they felt their life was in danger, and 42% had been referred to the ED by the emergency medical dispatch centre or their GP; 40% of patients were considered to be in a serious condition by ED physicians. The proportion of patients who were readmitted at 90 days was high but did not differ between the control and the HM intervention groups (31.7% vs 36.3, p=0.23). There was no significant difference in any of the secondary outcome measures between the control and HM intervention groups. Per-protocol analysis also showed no significant difference for the primary and secondary endpoints.
Conclusions: Although health mediation seemed to be a promising solution at the end of our qualitative study, this randomised controlled trial did not show that it was effective in reducing the use of emergency services by FUED living in precarious conditions. Interventions should screen these patients and aim to accurately identify their social, psychosocial and medical needs, involve ED staff and train them on the issue of precariousness, with a view to long-term health empowerment.
Trial registration: registered on clinicaltrials.gov as NCT03660215 on 4th September 2018
Electronic monitoring versus manual paper-based monitoring for hand hygiene compliance: A comprehensive health economic assessment analysis
Authors: Cheng Xiaolin , Li Yan , Chen Nuo , He Wenbin , Peng Hanzhi , Chen Xiaoyan , Cheng Fan , Tan Yibin , Yu Lina , Wu Wenwen , Wang Ying , Feng Bilong
Published: January 2024

Background: Monitoring hand hygiene compliance (HHC) of healthcare providers (HCPs) in healthcare facilities is critical for hand hygiene (HH) promotion. However, less is known about the cost and effectiveness of different HHC monitoring tools. In this study, we aimed to compare various health economic indicators corresponding to electronic system-based monitoring (ESM) and manual paper-based monitoring (MPM) for HHC to provide evidence-based advice for HHC monitoring measures targeted selecting.
Methods: A before and after self-controlled prospective study in 40 clinical departments with 4,524 HCPs was conducted from December 2022 to January 2023 (MPM implementation phase) and March 2023 to May 2023 (ESM implementation phase). The cost-effectiveness, cost-efficiency, the extent of the Hawthorne effect, and indirect cost-benefit of the two monitoring methods were compared.
Results: Compared with ESM, every 1% increase in the HHC of MPM resulted in a 39,881.62 CNY reduction in cost. Acceptability of ESM was higher when the cost was 40,000 CNY or less. The cost-efficiency ratio of MPM in all departments (155,775.56 CNY) was higher than that of ESM (36,796.76 CNY). The Hawthorne effect of MPM of HHC in all departments (43.99%) was more pronounced than that of ESM (35.69%), with a statistically significant difference(p < 0.01).
Conclusions: ESM exhibited notable advantages over MPM in terms of cost-effectiveness, cost-efficiency, cost-benefit, and the Hawthorne effect.
Effectiveness of multiple teaching methods in standardized training of internal medicine residents in China: a network meta-analysis
Authors: Ye Guan Cheng , Liu Chun Ping , Li Wei , Zhu Hua Chao , Lv Liu , Zhu Zhen Hong , Wang Yong Hong , Hu Jie , Zheng Xiao Jia , Fang Jing Ying , Ma Yu Cao , Liu Ming Xuan , Wang Yi Wen , Gao Ying Kai , Zhang Zi Yu , Zhao Lu Ming , Xie Cun Xiang , Lim Min Yee , Wang Hai-Long
Published: January 2024

Objective
Standardized training for resident physicians in China has been carried out for 10 years, and various new teaching methods have been widely applied in it. The quality of internal medicine teaching is directly related to whether the trainees can master the corresponding clinical skills well and become qualified clinical physicians. The purpose of this study is to systematically evaluate the effectiveness of all teaching methods in Chinese standardized training of internal medicine residents.
Methods
This study was registered in Inplasy. A comprehensive search of databases, including English and Chinese, was conducted from inception to 30 July 2023. Eligible studies included cohort study and randomized controlled trials (RCT) of all teaching methods in Chinese standardized training of internal medicine residents. A network meta-analysis (NMA) was performed using STATA 16.0. Statistical analysis was done using the mean and standard deviation. The literature quality and risks of bias was assessed using RevMan 5.3.
Results
A total of 74 articles including 5004 Chinese participants were retrieved, involving 13 interventions, of which 65 were RCT and 9 were cohort studies. This study found that the problem-based learning(PBL) + Wechat may be the best choice for improving students' academic performance, practical performance and reducing the number of dissatisfied individuals. The case-based learning(CBL) + Wechat has the most advantages in improving students' theoretical performance and reducing the number of dissatisfied individuals. The PBL + CBL may better improve students' self-learning ability and reduce the number of dissatisfied individuals.
Conclusion
New teaching methods represented by PBL + Wechat, CBL + Wechat, PBL + CBL are more effective in improving the academic performance of Chinese resident physicians in standardized training compared to control therapy, and have gained more recognition from students.
Examining Provider Practice-Level Disparities in Delivery Outcomes Among Patients with a History of Cesarean Delivery
Authors: McCarthy Lily , Tavella Nicola , Wetzler Sara , Ardente Lily , Chadwick Molly , Paul Dexter , Sabet Nikki , Stern Toni , Bianco Angela
Published: January 2024

Background
Choosing whether to pursue a trial of labor after cesarean (TOLAC) or elective repeat cesarean delivery (ERCD) requires prenatal assessment of risks and benefits. Providers play a central role in this process. However, the influence of provider-associated characteristics on delivery methods remains unclear. In this study we hoped to evaluate the impact of provider practice-level differences on delivery choice and outcome in a cohort of patients with prior cesarean delivery (CD).
Methods
This was a retrospective cohort study of deliveries between April 29, 2015 – April 29, 2020. Subjects were divided into three cohorts: ERCD, successful VBAC, and unsuccessful VBAC (patients who opted for TOLAC but delivered by CD). Disparities were reviewed between different obstetric provider practices, examining proportional differences through Chi-squared tests and logistic regression models. The delivering provider practice was determined from a breakdown of different providers delivering at the study site during the study period.
Results
1,765 deliveries were included in the study. There were significant proportional disparities between patients in the different delivery groups. Specifically, patients with a provider in a midwifery practice were significantly more likely to undergo successful VBAC, while patients seeing a private obstetrician were more likely to deliver by ERCD (p < 0.001). In our multivariate analysis of successful VBAC versus unsuccessful VBAC, patients delivered by the Refuah (16.62; 95%CI: 2.54, 30.61) and midwife (14.12; 95% CI: 2.83, 25.71) practices had greater odds ratios of VBAC compared to the private obstetrician group. In our multivariate analysis of unsuccessful VBAC versus ERCD, patients delivered by the Refuah (29.92; 95% CI: 9.92, 70.34) and house staff (2.35; 95% CI: 1.40, 4.00) practices had greater odds ratios of unsuccessful VBAC compared to the private obstetrician group.
Conclusion
This study suggests that provider practice-level differences may be one factor influencing CD rates. These data also illuminate under-researched areas in which culture influences maternal and neonatal delivery outcomes. These findings help to guide future investigations to improve outcomes among patients with a history of CD.
Trial Registration
Icahn School of Medicine at Mount Sinai, Program for the Protection of Human Subjects, STUDY ID 20–00633, Approved 6/17/2020
Metaverse in Dynamic Viral-shedding Surveillance for Emerging Infectious Disease: A Digital Twin Approach to COVID-19 Epidemic
Authors: Chen Hsiu Hsi , Lin Ting-Yu , Yen Ming-Fang , Chen Li-Sheng , Hsu Chen-Yang , Yeh Yen-Po
Published: January 2024

Metaverse in effective surveillance of outbreaks of emerging infectious diseases such as COVID-19 opens a new avenue for precision and efficient contact tracing, quarantine, and isolation. We adopted a digital twin model to generate digital threads for tracing and tracking virtual data on the cycle threshold (Ct) values of the repeated RT-PCR with parameters learned from real-world (physical) data fitted with Markov machine learning algorithms. Such a digital twin method is demonstrated with COVID-19 community-acquired outbreaks of the Alpha and Omicron Variants of Concern (VOCs) in Taiwan. The personalized dynamics of Ct-defined transitions were derived from the digital threads of the two community-acquired outbreaks to guide precision contact tracing, quarantine, and isolation of both Alpha and Omicron VOCs outbreaks. Metaverse surveillance with such a Ct-guided digital twin model is supposed to be useful for timely containing the spread of emerging infectious diseases in the future.
Group-based exercise for Parkinson’s: a qualitative study of participants’ and partners’ experiences from a community-university collaboration
Authors: Ferrusola-Pastrana Anna , Fullerton Christopher L , Meadows Stephen N
Published: January 2024

Community-based exercise programmes (CBEPs) are a practical and viable approach for providing people with Parkinson’s disease (PwP) with the opportunity to exercise as an ancillary therapeutic benefit to pharmacological management. This study aimed to explore the views and experiences of exercising participants (PwP) and non-participating partners involved in an exercise class delivered through a community-university partnership. Two separate focus group discussions were conducted: one with class participants (PwP: n = 7, H&Y scale I to III), and the other with non-participating partners of PwP (n = 4). The data were then thematically analyzed. Results suggest that a range of physical, psychological, and social factors were perceived to influence engagement: 1) Actively taking control, 2) Exercise is medicine for the mind and body, and 3) Working together as a team. Participants and partners felt that the support from the group, including the instructors and student volunteers, empowered and supported PwP to proactively self-manage their health, enjoy exercise in an inclusive group setting, and develop strong social connections with others in the local Parkinson’s community. Support for exercise from healthcare professionals was identified as both an enabler and barrier to participation. Critical reflections concerning its sustainability are offered, including implications for how exercise is considered as medicine for PwP, as well as some practical recommendations to galvanize community participation and provide inclusive and viable exercise opportunities for PwP.
Repeated γ Irradiation and Thermal Annealing via Built-In Thermo-Electric Coolers of Si Avalanche Photodiodes
Authors: Wu Shuin Jian , Chowdhury Arya , Soe Moe Thar , Ling Alexander
Published: January 2024

When operating in space, on-board Silicon Geiger-Mode Avalanche Photodiodes (GM-APDs) are exposed to radiation damage that result in an increase in dark count rates. Thermal annealing has been found to mitigate the damage, although prior studies have largely focused on annealing following a single session of proton irradiation. This work reports that thermal annealing can be performed simply with the built-in thermo-electric coolers of the GM-APDs. Annealing was also done in 10 min intervals for a clearer view of the recovery curve. Mitigation of damage from repeated γ radiation was observed from the: (1) halving of the increase in dark count rates on average and (2) outperformance of room temperature annealing (25°C) by 33%. Additionally, we show that heavy doses of γ radiation (21 krad) have a probability of causing Random Telegraph Signals in GM-APDs that can be suppressed by lowering the operating temperature.
Prevalence and molecular characterization of Trichomonas gallinae from pigeons in Anhui, China
Authors: Zhang Yilei , Lu Zhenxiao , Liu Zhenzhen , Zhou Yuhan , Xiao Guodong , Opeyemi Ayanniyi Olalekan , Jin Sihua , Li Yongsheng , Liu Tao , Wu Qiong , Sun Xingdong , Xu Qianming , Zhang Qingxun , Yang Congshan
Published: January 2024

Trichomonas gallinae, a protozoan parasite causing avian trichomonosis, exhibits a widespread global prevalence. It primarily affects the upper digestive tract of birds and has resulted in significant ecological problems worldwide. This study aimed to investigate the prevalence and genotypes of T. gallinae in Anhui Province, China. A total of 1612 oropharyngeal swab samples were collected from pigeon farms in Anhui Province to determine the prevalence of T. gallinae infection. The results revealed 565 (35.1%) positive samples of T. gallinae. Significant differences in infection rates were observed among different regions and age groups. Furthermore, the ITS1/5.8S/ITS2 region was amplified, sequenced, and subjected to phylogenetic analysis. Genotypes A and B of T. gallinae were identified, and genotype B was the dominant genotype in Anhui Province. This is the first report on the prevalence and molecular characterization of T. gallinae in Anhui Province, China. Additionally, we integrated reports on the prevalence and genotype of T. gallinae in relevant provinces in China.