bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencing
Authors: Huo Jingyuan , Wang Zhen , Zhao Wenting , Chen Miao , Li Haoyang , He Fengpu , Tian Xiao , Ma Yaqi , Husanova Firyuza , Ma Liang , Ni Yiming , Ding Hongda , Li Weidong , Xu Hongfei
Published: December 2024

Background

Primary cardiac angiosarcoma (PCAS) is a rare and aggressive heart tumour with limited treatment options and a poor prognosis. Understanding cellular heterogeneity and tumour microenvironment (TME) is crucial for the development of effective therapies. Here, we investigated the intratumoural heterogeneity and TME diversity of PCAS using single‐cell RNA sequencing (scRNA‐seq).

Methods

We performed scRNA‐seq analysis on tumour samples from four patients with PCAS, supplemented with multicolour immunohistochemistry for identification. We used scRNA‐seq data from five normal cardiac tissue samples downloaded from public databases for comparative analyses. Bioinformatic analyses, including Cell Ranger, Seurat, Monocle2, hdWGCNA, SCENIC and NicheNet, were utilized to identify distinct cell populations, transcriptional patterns, and co‐regulating gene modules.

Results

Our analysis revealed significant intratumoural heterogeneity in PCAS driven by diverse biological processes such as protein synthesis, degradation, and RIG‐I signalling inhibition. The SCENIC analysis identified three primary transcription factors' clusters (CEBPB, MYC and TAL1). T‐cell subset analysis showed exhausted antigen‐specific T‐cells, complicating the efficacy of immune checkpoint blockade. Furthermore, we observed suppressive macrophages (SPP1+ and OLR1+) and reduced mitochondrial gene MT‐RNR2 (MTRNR2L12) expression in TME‐infiltrating cells, indicating impaired mitochondrial function.

Conclusion

This study elucidates the complex cellular landscape and immune microenvironment of PCAS, highlighting potential molecular targets for the development of novel therapies. These findings underscore the importance of a multifaceted therapeutic approach for addressing the challenges posed by PCAS's heterogeneity and immune evasion.

Key points

Insights into the heterogeneity and transcriptional patterns of sarcoma cells may explain the challenges in treating primary cardiac angiosarcoma (PCAS) using the current therapeutic modalities.

Characterization of the immune microenvironment revealed significant immunosuppression mediated by specific myeloid cell populations (SPP1+ and OLR1+ macrophages).

Identification of mitochondrial dysfunction in immune cells within the PCAS microenvironment, particularly the notable downregulation of the MTRNR2L12 protein, suggests a new avenue for therapeutic targeting.
Epithelial NSD2 maintains FMO‐mediated taurine biosynthesis to prevent intestinal barrier disruption
Authors: Xu Yue , Xiao Xiuying , Ma Chunxiao , Wang Ziyi , Feng Wenxin , Rao Hanyu , Zhang Wei , Liu Ningyuan , Aji Rebiguli , Meng Xiangjun , Gao Wei‐Qiang , Li Li
Published: December 2024

Background

Inflammatory bowel disease (IBD) presents a significant challenge due to its intricate pathogenesis. NSD2, a histone methyltransferase responsible for dimethylating histone 3 at lysine 36, is associated with transcriptional activation. NSD2 expression is decreased in both the intestinal epithelial cells (IECs) of IBD patients and the IBD mouse model. However, the precise role of NSD2 in IBD remains unexplored.

Methods

Colon tissues from IBD mice, SW620 cells and MC38 cells, were used as research subjects. Clinical databases of IBD patients were analysed to investigate whether NSD2 expression is reduced in the occurrence of IBD. NSD2‐knockout mice were generated to further investigate the role of NSD2 in IBD. The IECs were isolated for RNA sequencing and chromatin immunoprecipitation sequencing to identify molecular signalling pathways and key molecules leading to IBD in mice. Molecular and cellular experiments were conducted to analyse and validate the role of NSD2 in the development of IBD. Finally, rescue experiments were performed to confirm the molecular mechanism of NSD2 in the development of IBD.

Results

Deficiency of NSD2 in mouse IECs aggravated epithelial barrier disruption and inflammatory response in IBD. Mechanistically, NSD2 loss led to downregulation of H3K36me2 and flavin‐containing monooxygenase (FMO) (taurine‐synthesis enzyme) mRNA, resulting in decreased taurine biosynthesis in IECs. Significantly, supplementation with taurine markedly alleviated the symptoms of NSD2 deficiency‐induced IBD.

Conclusions

These data demonstrate that NSD2 plays a pivotal role in maintaining FMO‐mediated taurine biosynthesis to prevent intestinal inflammation. Our findings also underscore the importance of NSD2‐H3K36me2‐mediated taurine biosynthesis in maintaining intestinal mucosal barrier homeostasis.

Key points

In this study, we investigated the role of the histone methyltransferase NSD2 in preventing intestinal barrier disruption by sustaining taurine biosynthesis. NSD2 levels were reduced in both human specimens and mouse models of IBD. We demonstrate that NSD2 loss hinders the process of taurine synthesis in intestinal cells, leading to increased intestinal inflammation.

Supplementation with taurine significantly relieved the symptoms caused by NSD2 deficiency. These data suggest that maintenance of NSD2‐mediated taurine biosynthesis is vital for preserving the intestinal barrier and attenuating inflammation.
Design and Discovery of New Dual Carbonic Anhydrase IX and VEGFR‐2 Inhibitors Based on the Benzenesulfonamide‐Bearing 4‐Thiazolidinones/2,4‐Thiazolidinediones Scaffold
Authors: Zengin Merve , Unsal Tan Oya , Sabuncuoglu Suna , Arafa Reem K. , Balkan Ayla
Published: December 2024

Dual‐targeting drug design has become a popular approach in investigating and developing potent anticancer agents. In this regard, carbonic anhydrase (CAIX) and vascular endothelial growth factor receptor (VEGFR‐2) are emerging as highly effective targets in the battle against cancer. In the present study, two series of 4‐thiazolidinones/2,4‐thiazolidinediones carrying 2‐methylbenzenesulfonamide derivatives were designed and synthesized as potential dual CAIX/VEGFR‐2 inhibitors. All the target compounds were evaluated against CAIX enzyme compared to dorzolamide and acetazolamide, subsequently the most potent CAIX inhibitors (3a, 3b, 3o, 6d, 6g, and 6i) were selected to evaluate their inhibitory activity against VEGFR‐2 using sorafenib as a reference drug. These compounds were also evaluated against MCF‐7 breast cancer cells and the murine fibroblast 3T3 cell line. According to the results, 3b (CAIX IC50 = 0.035 µM, VEGFR‐2 IC50 = 0.093 µM) and 6i (CAIX IC50 = 0.041 µM, VEGFR‐2 IC50 = 0.048 µM) emerged the most potent compounds against CAIX and VEGFR‐2. Furthermore, docking studies of selected compounds were performed with the CAIX and the tyrosine kinase domain of VEGFR‐2 to comprehend the ligand‐binding interactions. Physicochemical predictions were examined using in silico techniques. In conclusion, these scaffolds present promising leads and furnish promising chemical backbones for the design of potent dual CAIX and VEGFR‐2 inhibitors.b
Get it while it's hot: Benefits of a large herbivore exploiting stochastic resource pulses in a time of food scarcity
Authors: Dwinnell Samantha P. H. , Beumer Larissa T. , van der Wal René , Albon Steve D. , Pedersen Åshild Ø. , Holand Øystein , Hansen Brage B. , Irvine R. Justin , Ropstad Erik , Veiberg Vebjørn , Loe Leif Egil
Published: December 2024

To persist in seasonal environments, animals track, exploit, and store energy when food is plentiful. Seasonal changes in plant phenology that are predictable allow animals to track abundant food resources. However, little is known about how animals use and benefit from ephemeral and unpredictable food pulses during times when food is scarce. Climate change is altering the timing, abundance, and spatial distribution of food releases, emphasizing the ongoing need for understanding how unseasonal weather conditions influence access to food. Using 12 years of GPS‐location data and annual measures of body mass in 72 adult female Svalbard reindeer (Rangifer tarandus platyrhynchus), we tested whether individuals with greater use of nutritionally beneficial resource pulses in autumn and early winter are heavier going into parturition in spring. Additionally, we evaluated how stochastic weather conditions influence the use of food resources. Reindeer that foraged most in marshes during autumn and early winter gained a positive carryover effect of up to 5 kg heavier body mass in late winter, with previously demonstrated benefits to both survival and reproduction. Marsh use was rare, brief, and intense, which is the expected response to a pulsed resource. The extent to which marshes were used varied greatly among years and was associated with stochastic mild spells that relaxed constraints of snow depth for a few days. Compared with other habitats used, marshes offered superior quantity and quality of belowground plant biomass that may be accessed more easily under milder autumn and winter conditions. Our findings demonstrate the individual benefits of exploiting stochastic food pulses and showcase how resource tracking during periods of food scarcity may be a behavioral trait that could enhance population resilience in a rapidly warming climate.
Using Gap Visualization to Navigate Multivariate Metabarcode Data, Select Primer Pairs, and Enhance Reference Data Quality
Authors: Chua Xin‐Yi , Ord Louise , Bent Stephen J. , Lovell David , McGrath Annette
Published: December 2024

The success of amplicon sequencing studies of environmental DNA (eDNA) depends on the choice of primer pairs used to select taxa‐specific regions of DNA for amplification then sequencing to characterize sample composition. This paper presents practical methods to visualize the extent to which different primer pairs can differentiate taxonomic groups, enabling researchers to assess which primers might be best suited for a study or environment of interest. These methods can also be used to review taxonomic annotations in genomic reference sequence databases. We apply the concept of DNA barcoding gaps to metabarcoding of multiple species in environmental DNA to leverage reference data on the amplicon sequences of previously characterized specimens. Since reference data sets are large and complex, we provide a simple and intuitive method to navigate subsets of reference sequence data containing conflicting or ambiguous relationships between genomic information and taxonomic classification. We demonstrate how to use gap visualization and taxonomic segmentation in comparing how well different primer pairs discriminate species of interest, and in detecting anomalies in reference sequence annotation. We show how these visualization methods can enable amplicon survey study design and make fundamental molecular resources more accessible to a wider research audience beyond bioinformaticians and data scientists.
From Enzyme Encapsulation to Environmental Solutions: Photostable Laccase in Dopc Vesicles
Authors: Luna M. Alejandra , Reynoso Eugenia , Biasutti M. Alicia , Montejano Hernán A. , Moyano Fernando , Correa N. Mariano
Published: December 2024

The laccase enzyme offers significant advantages for the removal of organic contaminants; but its stability and effectiveness in bioremediation can be compromised by photo‐induced degradation processes. To address this challenge, we investigated the immobilization of laccase in unilamellar and multilamellar vesicles of dioleoyl phosphatidylcholine (DOPC) as a means to enhance its photo‐stability while preserving its catalytic activity. Enzymatic activity was evaluated spectroscopically for both free and encapsulated laccase, before and after UVB irradiation. Our results demonstrate that DOPC vesicles effectively encapsulate the laccase enzyme, maintaining its activity within the vesicles. Moreover, the substrate syringaldazine, a model compound for laccase activity studies, was able to permeate through the bilayer. Notably, encapsulated laccase exhibited significantly higher retention of enzymatic activity (REA) post‐irradiation compared to the free enzyme. In conclusion, both unilamellar and multilamellar vesicles provide substantial photoprotection for laccase against UVB light. This protective effect is attributed to the enzyme's confinement within a system that scatters high‐energy photons. Furthermore, the simplicity and ease of large‐scale production of multilamellar vesicles present an advantageous option for various applications, including bioremediation.
Biowaste Sea Shells‐Based Triboelectric Nanogenerator: Sustainable Approach for Efficient Mechanical Energy Harvesting
Authors: Vikram Lakshmi Suneetha , Potu Supraja , Kasireddi A. K. Durga Prasad , Khanapuram Uday Kumar , Divi Haranath , Rajaboina Rakesh Kumar
Published: December 2024

Waste‐to‐energy research is crucial for reducing environmental pollution and achieving a greener planet. Among many waste‐to‐energy technologies, triboelectric nanogenerators (TENGs) have attracted much attention in using waste materials for energy production in the last decade. This study presents the first reported use of biowaste sea shells (BSS) in the development of TENGs. For the fabrication of the TENG, BSS powder is attached to aluminum tape to act as one triboelectric layer and silicone rubber to serve as the opposite triboelectric layer. The BSS‐TENG device produces an output voltage and current of ≈200 V and 40 μA, respectively. The power density achieved by the fabricated TENG is 948 mW m−2. The output of the TENG is utilized in a powering series connected 240 LEDs momentarily for each tapping. This study not only offers a sustainable and cost‐effective material for TENG assembly, but also opens up new avenues for research into energy harvesting utilizing biowaste, with the potential for future applications in powering small‐scale devices and contributing to sustainable energy solutions.
Synthesis‐Driven Enhancement in Energy Storage Performance of Copper Transition Metal Phosphates for Hybrid Battery‐Supercapacitor Systems
Authors: Ahmed Anique , Abdul Karim Muhammad Ramzan , Usman Muhammad
Published: December 2024

The tremendous advancements in science and technology have resulted in the invention of electronic devices that require greater energy storage capabilities. Hybrid supercapacitors (SCs) gain promising interest due to their exceptional electrochemical performance similar to batteries (high‐energy density) and SCs (high‐power density). The excellent performance of the electrode material is significantly influenced by the employed synthesis route. The copper phosphate (Cu3(PO4)2) nanomaterials are synthesized using hydrothermal and sonochemical techniques. Two‐ and three‐electrode configurations are utilized to evaluate the electrochemical performance of the as‐prepared nanomaterials. An incredible specific capacity of 443.86 C g−1 at 1.4 A g−1 is achieved through sonochemically obtained nanomaterial (S2). In two‐electrode configuration, S2 is used as a positive electrode material to fabricate an asymmetric device, which provides an energy density of 51.2 Wh kg−1 and power density of 6800 W kg−1 at 0.9 and 8.0 A g−1, respectively. The device also demonstrates an exceptional capacity retention of 93.45% after 1000 galvanostatic charge–discharge cycles at 5 A g−1. Overall, the outcomes suggest that the sonochemical method is the most effective approach for the preparation of nanomaterials for next‐generation energy storage applications.
Effect of supersaturation distribution on particle heterogeneous condensation in growth tube
Authors: Dai Anwen , Zhang Jun , Li Anjin
Published: December 2024

Supersaturation is a critical factor influencing the growth of fine particles in heterogeneous nucleation processes. To further investigate its effects on particle growth behavior, this study employs numerical simulations, coupling the particle growth rate equation with a population balance model to systematically analyze the impact of various supersaturation distributions on particle growth. The results indicate that, in the axial direction, the closer the supersaturation peak is to the outlet of the growth tube, the more effective the particle growth, with a maximum increase of 10.20%. In the radial direction, higher supersaturation near the tube wall results in better particle growth at the outlet, with a maximum increase of 28.70%. A more uniform supersaturation field is found to promote particle growth. Conversely, when the supersaturation near the wall is relatively low, particles are less likely to be effectively activated, leading to restricted growth. Additionally, this paper explores the growth of fine particles under different supersaturation field configurations, demonstrating the generality of the observed patterns.
Experimental and numerical investigation of water flow behaviour in sharply curved 60° open‐channel bends
Authors: Seyedashraf Omid , Akhtari Ali Akbar
Published: December 2024

Understanding secondary flows in sharply curved open‐channel bends is key for analysing the flow patterns in rivers and and designing effective hydraulic structures. This study employs both experimental and computational methods to investigate the flow characteristics in a sharply curved 60° open‐channel bend. The primary objective is to enhance understanding of flow behaviours in such configurations. For numerical simulations, we utilize the Reynolds‐averaged Navier–Stokes equations, applying the volume‐of‐fluid free surface model to simulate air‐water interactions alongside the standard k‐ε and renormalized group (RNG) k‐ε turbulence models. Our findings reveal the emergence of helical currents driven by centrifugal forces at the bend's onset, which guide the fluid particles from the channel bottom to the convex (inner) bank and then to the concave (outer) bank at the surface. We observe a progressive increase in secondary flow intensity and energy dissipation along the bend, peaking at the terminal section. Notably, maximum flow velocity occurs near the convex wall accompanied by nonlinear water surface behaviours. Additionally, flow separation tendencies near the convex wall are noted after two‐thirds of the curvature. Quantitatively, the flow velocity at the convex bank was observed to be 1.70 times higher than at the concave bank within the bend. The mean absolute errors between experimental data and the standard k‐ε and RNG k‐ε models are 3.20 and 3.12, respectively, indicating the accuracy of the RNG k‐ε model.
Impact of vitamin A on the risk of mild cognitive impairment and Alzheimer's disease pathology in high‐fat‐diet–treated APP/PS1 mice
Authors: Wang Xixiang , Guo Yujie , Li Pengfei , Ma Xiaojun , Xu Jingjing , Liu Lu , Liu Yu , Ren Xiuwen , Wang Ying , Meng Liping , Zhou Shaobo , Yuan Linhong
Published: December 2024

Abnormal glucose metabolism and vitamin A (VA) nutritional status promote the occurrence of cognitive impairment and Alzheimer's disease (AD). However, the effects of low VA intake, insulin resistance, and their interaction on the promoting cognitive impairment remain unclear. This population‐based study was conducted to explore the relationship between circulating VA levels with cognitive performance in T2DM subjects. Moreover, APP/PS1 mice were treated with a low VA diet to investigate the effect and mechanism of VA deficiency on glucose and Aβ metabolism in the brain. Low blood VA levels correlated with an increased risk of mild cognitive impairment in both non‐T2DM and T2DM subjects, and T2DM patients need much higher circulating VA levels to maintain normal cognitive function. High‐fat diet induced insulin resistance in APP/PS1 mice, and this impact was further enhanced by a low VA diet. A synergistic deteriorated impact of a high‐fat diet and low VA intake on AD‐like pathology was observed in APP/PS1 mice, which was demonstrated by increased cortical BACE1 expression and Aβ level and decreased IRS1 expression. Our results suggest that the nutritional status of VA is associated with cognitive performance in the elderly and synergistically enhances the pathological phenotypic changes in APP/PS1 mice treated with a high‐fat diet.
N6,N6‐Dimethyl‐l‐Lysine: An Anti‐Obesity Metabolite of Lactiplantibacillus plantarum R2‐5 From Longevity Area Revealed by Multi‐Omics Analysis
Authors: Su Man , Zhao Lina , Li Chen , Zhang Na , Liu Yajing , Li Yuwei , Wang Miaoshu , Kang Hongyan , Li Dongyao , Tian Hongtao
Published: December 2024

Lactobacilli bacteria, as probiotics, show significant potential for lipid reduction. Current research into their lipid‐lowering effects is in the early stages, with mechanisms largely unexplored. In this study, mice were induced with a high‐fat diet (HFD) and treated with Lactiplantibacillus plantarum R2‐5 (LPR2‐5) via oral gavage. After 12 weeks, the LPR2‐5‐treated group exhibited substantial improvements in body weight and lipid abnormalities, with significant reductions in liver and abdominal fat accumulation. (LPR2‐5 can reduce serum total cholesterol [TC] by 25.7%, lower triglycerides [TG] by 45%, decrease low‐density lipoprotein cholesterol [LDL‐C] by 30%, and double high‐density lipoprotein cholesterol [HDL‐C].) Analysis of gut microbiota diversity demonstrated that LPR2‐5 intervention altered the gut microbiome, increasing the abundance of short‐chain fatty acid (SCFA)‐producing bacteria (Lactobacillus, Roseburia) and potentially beneficial microbes (Turicibacter, Christensenella), while inhibiting obesity‐associated bacteria (Alistipes, Bilophila), thus altering metabolic activity in the gut. Using multi‐omics techniques, key metabolic pathways and metabolites were identified. The lipid‐lowering mechanism involved a notable increase in N6,N6‐dimethyl‐l‐lysine, a precursor for carnitine synthesis, enhancing carnitine production in the liver and promoting β‐oxidation of long‐chain fatty acids, thereby effectively reducing early stage adipose accumulation.
Quality Controls: The Role of Self‐Corrective Science in Explorations of Primate Memory Systems
Authors: Murray Elisabeth A.
Published: December 2024

In 1978, Mort Mishkin published a landmark paper describing a monkey model of H.M.'s dense, global amnesia. It depended on a combined removal of the amygdala and hippocampus (the A + H lesion) and a memory test called delayed nonmatching‐to‐sample (DNMS). My first project examined whether the impairment Mishkin had found in visual memory generalized to tactual stimuli. However, to gain access to the hippocampus and amygdala with 1980s surgical methods, we had to remove the underlying cortex. When we were able to test the effects of bilateral removal of that underlying cortex (the entorhinal and perirhinal cortex, or “rhinal cortex” for short) we obtained a dramatic result. This so‐called “control” lesion caused a profound impairment on the DNMS task. A few years later, excitotoxic A + H lesions, which left the rhinal cortex intact, confirmed that removal of the cortical “impediments” had caused the entire memory impairment that Mishkin had observed. These results: (1) forced a reconsideration of the monkey model of global anterograde amnesia; (2) spurred study of the independent contributions of the amygdala, hippocampus, and perirhinal cortex to cognition; and (3) led to the realization that the DNMS task did not test the kinds of memory that H.M. lost after his surgery.
Effectiveness of video self‐monitoring for training and maintaining procedural fidelity during covert observations
Authors: Paden Amber R. , Carroll Regina A.
Published: December 2024

Previous research has shown that low procedural fidelity can lead to decreased effectiveness and efficiency of skill acquisition during discrete‐trial instruction. Previous research has also found that procedural fidelity may be substantially lower when a supervisor is not present to observe the session. Finding a socially acceptable, effective, and efficient method to increase and maintain high levels of staff members' procedural fidelity during covert observations is critical in the clinic setting. The purpose of the current study was to examine the effectiveness of video self‐monitoring in increasing and maintaining high procedural fidelity among staff who implement discrete‐trial instruction during covert and overt observations. Participants included four staff members working one‐on‐one with children with autism spectrum disorder. The results show that video self‐monitoring was effective at increasing staff members' procedural fidelity and maintaining high fidelity over time.
On the prevalence and magnitude of resurgence during delay‐and‐denial tolerance teaching
Authors: Marshall Arielle R. , Mitteer Daniel R. , Greer Brian D. , Kishel Catherine B.
Published: December 2024

Resurgence is the recurrence of target behavior (e.g., challenging behavior) during a worsening of reinforcement conditions (e.g., increases in response effort, decreases in alternative reinforcement). Previous studies have examined the prevalence and magnitude of resurgence during functional communication training implemented with discriminative stimuli. We conducted a systematic review of the literature to analyze the magnitude and prevalence of resurgence during delay‐and‐denial tolerance teaching. Similar to previous studies with discriminative stimuli, resurgence occurred for most participants and in about one third of transitions. When resurgence was present, challenging behavior increased to approximately 26% of baseline levels. Resurgence was less likely to occur during response‐effort manipulations (i.e., complexity teaching, tolerance‐response teaching) and was most likely to occur during increases in delays that ended following the passage of time rather than a response criterion. We discuss implications for treatment refinements and future treatment‐relapse research.
Clinical impact of a tiered, pharmacist‐driven remote patient monitoring protocol utilizing self‐measured blood pressure readings
Authors: Hovis Zachary , Hanson Ryan , DeJarlais Erin
Published: December 2024

Introduction

Pairing self‐measured blood pressure (SMBP) with protocolized, non‐physician follow‐up consistently improves hypertension (HTN) management. However, these interventions are often resource‐intensive and rely on a degree of technological proficiency that may exclude a vulnerable subset of the population.

Objectives

The primary objective of this study was to determine the rate of attainment of blood pressure (BP) control (defined as <140/<90 mmHg) based on the most recent clinic‐measured BP readings 12 months or more after enrollment in the Digital Care Monitoring program. The secondary objective was to determine if there was a difference between the most recent clinic‐measured systolic and diastolic BP readings before enrollment compared with 12 months or more after the enrollment eligibility period.

Methods

This study examined the impact of a tiered, non‐physician SMBP program, engaging patients through a familiar communication medium to relay home BP readings. A pre‐post quality improvement study was conducted in the outpatient arm of an integrated delivery network. Patients meeting selection criteria were invited to voluntarily enroll bi‐monthly from October 2021 to July 2023. Patients consenting to enrollment received reminders twice weekly to respond with home BP readings, and an outreach protocol was established utilizing a medical assistant and clinical pharmacist.

Results

The rate of attainment of BP control 12 months or more after the enrollment eligibility period was found to be 79.2% (p < 0.01). BP dropped significantly over the 12‐month treatment course with a mean systolic BP difference of 19.97 mmHg (p < 0.001) and a mean diastolic BP difference of 12.34 mmHg (p < 0.001).

Conclusion

The results indicate that a tiered, pharmacist‐driven remote patient monitoring protocol utilizing SMBP readings is an effective management strategy to reduce BP in patients with uncontrolled HTN.
Prescribing practices and barriers to use of sodium‐glucose cotransporter 2 inhibitors and glucagon‐like Peptide‐1 receptor agonists in adult kidney transplant recipients: A survey of endocrinology and nephrology prescribers
Authors: Walter Krysta , Choksi Palak , Papaleontiou Maria , Low Wang Cecilia C. , Gumber Ramnika , Park Jeong M.
Published: December 2024

Clinical practice variability exists regarding the use of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) in kidney transplant recipients (KTRs). The objective of this study was to understand prescribing practices and barriers for the use of SGLT2i and GLP‐1RA among endocrinology and nephrology prescribers caring for KTRs. A 19‐item electronic survey assessing prescribing practices and barriers for the use of SGLT2i and GLP‐1RA in adult KTRs was distributed to all members of the Planning Research in Inpatient Diabetes/Planning Research in Outpatient Diabetes (PRIDE/PROUD) group and the American Society of Transplantation Kidney Pancreas Community of Practice via email listservs between July and November 2023. Endocrinology and nephrology prescribers caring for adult KTRs with type 2 diabetes mellitus (T2DM) or post‐transplant diabetes mellitus (PTDM) were eligible. A total of 50 responses were included for analysis (n = 25 endocrinology, n = 25 nephrology). Respondents prescribed SGLT2i and GLP‐1RA to adult KTRs with T2DM/PTDM with the following frequency: always (4% SGLT2i, 6% GLP‐1RA), often (34% SGLT2i, 30% GLP‐1RA), sometimes (34% SGLT2i, 36% GLP‐1RA), rarely (22% SGLT2i, 20% GLP‐1RA), or never (6% SGLT2i, 8% GLP‐1RA). The most common indication for both drug classes was diabetes mellitus (DM)/hyperglycemia (84% SGLT2i, 90% GLP‐1RA). Most prescribers felt comfortable initiating a SGLT2i (58%) or GLP‐1RA (62%) between 1 and 6 months post‐transplant. Prescribers were always or often concerned about infection (67%) with the use of SGLT2i and gastrointestinal intolerance (66%) with GLP‐1RA. Cost of treatment/insurance coverage/need for prior authorization and patient concern for drug cost was identified as being very likely or likely barriers for prescribing these drug classes post‐transplant (54% SGLT2i, 62% GLP‐1RA). SGLT2i and GLP‐1RA are prescribed mainly for DM/hyperglycemia by endocrinology and nephrology prescribers between 1 and 6 months postkidney transplant. Concerns surrounding medication access and cost were the most frequently reported barriers to use.
Regulation of the Cilia as a Potential Treatment for Senescence and Tumors: A Review
Authors: Zhu Danping , Pan Yuqin , Yang Yong , Wang Shukui
Published: December 2024

Millions of people worldwide die from malignant tumors every year, and the current clinical treatment is still based on radiotherapy and chemotherapy. Immunotherapy‐adjuvant chemotherapy is widely applied, yet resistance to various factors persists in the management of advanced malignancies. Recently researchers have gradually discovered that the integrity of primary cilia is closely related to many diseases. The phenotypic changes in primary cilia are found in some cases of progeria, tumorigenesis, and drug resistance. Primary cilia seem to mediate signaling during these diseases. Hedgehog inhibitors have emerged in recent years to treat tumors by controlling signaling proteins on primary cilia. There is evidence for the use of anti‐tumor drugs to treat senescence‐related disease. Considering the close relationship between aging and obesity, as well as the obesity is the phenotype of many ciliopathies. Therefore, we speculate that some anti‐tumor or anti‐aging drugs can treat ciliopathies. Additionally, there is evidence suggesting that anti‐aging drugs for tumor treatment, in which the process may be mediated by cilia. This review elucidates for the first time that cilia may be involved in the regulation of senescence, metabolic, tumorigenesis, and tumor resistance and hypothesizes that cilia can be regulated to treat these diseases in the future.
Translocal Livelihoods, Socio‐Economic Differentiation and Lower Level Urbanisation in Uganda
Authors: Andersson Agnes , Mackay Heather , Mukwaya Paul Isolo
Published: December 2024

In sub‐Saharan Africa, more than a quarter of the urban population lives in small towns, with rapid lower level urbanisation being driven largely by lacking rural opportunities. A growing interest in translocality considers relationships that position livelihoods within multiple spatial contexts. Terms of inclusion in translocal relationships vary, and the socio‐economic differentiation emerging out of these relationships is understudied. We use a mixed‐methods approach, combining survey data with qualitative data collected in seven small towns in Uganda to shed light on their translocal livelihood dynamics and to elucidate the empirical and theoretical linkages between translocality and socio‐economic differentiation.
Investigating the causal links between inflammatory cytokines and scoliosis through bidirectional Mendelian randomization analysis
Authors: Mardan Muradil , Mamat Mardan , Yasin Parhat , Cai Xiaoyu , Zheng Huoliang , Xu Qingyin , Song Shaokuan , Li Bo , Cai Hao , Chen Pengbo , Lu Zeyu , Omar Shahna , Jiang Shengdan , Jiang Leisheng , Zheng Xin‐feng
Published: December 2024

Background

Scoliosis, characterized by a lateral curvature of the spine, affects millions globally. The role of inflammatory cytokines in the pathogenesis of scoliosis is increasingly acknowledged, yet their causal relationships remain poorly defined.

Aims

This study aims to explore the genetic‐level causal relationships between inflammatory cytokines and scoliosis utilizing bidirectional Mendelian randomization (MR) analysis.

Materials and Methods

This study leverages genetic data from public Genome‐Wide Association Studies (GWAS). Bidirectional MR was employed to investigate the causal relationships between 44 inflammatory cytokines and scoliosis. The inflammatory cytokine data include 8293 Finnish individuals, while the scoliosis data consist of 165 850 participants of European descent, including 1168 scoliosis cases and 164 682 controls. Causal links were assessed using the inverse variance‐weighted method, supplemented by MR‐Egger, weighted median, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using standard tests, with sensitivity analysis conducted through leave‐one‐out analysis.

Results

Our analysis demonstrated a significant causal association between the cytokine Resistin (RETN) and the development of scoliosis (p = 0.024, OR 95% CI = 1.344 [1.039–1.739]). No other cytokines among the 44 studied showed significant associations.

Discussion

The findings highlight the critical role of RETN in scoliosis progression and underscore the complex interplay of genetic and inflammatory pathways. Further research is needed to explore additional biomarkers and their mechanisms in scoliosis.

Conclusion

This study provides evidence of a significant causal relationship between RETN and scoliosis, emphasizing its potential as a therapeutic target. These findings contribute to understanding scoliosis pathogenesis and pave the way for future research on inflammation‐related pathways and therapies.
Discovering the Bioactive Compounds Binding to α1A‐Adrenergic Receptor in Guizhi Fuling Formula and Revealing Their Interactions by Immobilizing the Receptor Through Colicin L7 DNase/Immunity Protein 7 Ultra‐Affinity System
Authors: Ji Xu , Li Liangxi , Zhang Kaiyue , Yuan Xinyi , Zhang Xiaoying , Wang Lu , Zhao Qin
Published: December 2024

In this work, Guizhi Fuling Formula (GFF), as well as α1A‐adrenergic receptor (α1A‐AR) were taken as the research objects. By utilizing the ultra‐affinity between Colicin L7 DNase (CL7) and its homologous immune protein 7 (Im7), CL7‐tagged α1A‐AR was oriented immobilized to the Im7‐coated silica gel surface. With the α1A‐AR immobilized column in hand, the active compounds in GFF targeted to α1A‐AR were screened, and the binding procedures were analyzed. The composite characterization demonstrated that the α1A‐AR can be immobilized to the chromatographic stationary phase with good specificity and stability in 3 weeks. Paeoniflorin, cinnamic acid, and paeonol were identified as the active compounds in GFF targeted to α1A‐AR. Among them, cinnamic acid and paeonol have the same binding site on α1A‐AR as the specific drug tamsulosin. The binding parameters obtained by frontal analysis and injection amount‐dependent analysis were consistent in the same concentration range. Collectively, these results indicated that the α1A‐AR chromatographic column synthesized by a novel immobilized method was capable of screening and analyzing the functional compounds from the complex matrix, which provided an alternative for rapid screening and analysis to traditional ethnic drugs.
An Alginate/Gelatin Injectable Hydrogel Containing Au Nanoparticles for Transplantation of Embryonic Mouse Cardiomyocytes in Myocardial Repair
Authors: Pournemati Behnam , Tabesh Hadi , Mehdinavaz Aghdam Rouhollah , Rezayan Ali Hossein , Poorkhalil Ali , Ahmadi Tafti Seyed Hossein , Heirani‐Tabasi Asieh , Eyni Hossein , Malekmohamadi Marjan , Boroumand Safieh , Pinna Alessandra
Published: December 2024

In advancing cardiac tissue engineering (CTE), the development of injectable hydrogels mirroring myocardial properties is pivotal. The designed hydrogels must not only support cardiac cell growth but also have to be conductive to properly promote the functionalities of cardiac cells. Here, a facile approach is developed to incorporate gold nanoparticles (AuNPs) into an injectable hydrogel composed of Alginate (Alg) and Gelatin (Gel). The resultant nanocomposite hydrogel boasts a porous interconnected network and superior conductivity (2.04 × 10–4 S cm−1) compared to the base Alg/Gel hydrogel. Hydrogel hydration and in vitro degradation profiles affirm their suitability as carriers for cardiac cells. Importantly, Alg/Gel+AuNPs hydrogels exhibit no toxicity to mouse Embryonic Cardiac Cells (mECCs) over 7 days, elevating connexin 43 (Cx43) and cardiac troponin T (CTnT) gene expression compared to controls. Then, the Alg/Gel+AuNPs hydrogel is used as a carrier for intramyocardial delivery of mECCs in rats with myocardial infarction. The significant increase in α‐Smooth Muscle Actin (α‐SMA) and cardiac troponin T (CTnT) expression along with the increase in ejection fraction (EF), smaller infarction size, less fibrosis area confirmed that the hydrogel efficiently promoted the transmission of mechanical and electrical signals between transplanted cells and surrounding tissue.
Engineering RAFT Polymers to the Protein‐capped Gold Nanoclusters for Developing Fluorescent Polymeric Nanoconjugates
Authors: Gaddala Raviteja , Chelluboyina Aruna Kumar , Kumar Sonu
Published: December 2024

The synthesis of fluorescent hybrid nanomaterials engineered via the chain‐end modification of reversible addition‐fragmentation chain‐transfer (RAFT) polymers on the surface of bovine serum albumin (BSA) protein‐stabilized gold nanoclusters (AuNCs@BSA) is described. Based on the “grafting‐to” approach the core‐shell structured nanoconjugates AuNCs@BSA/polymer are generated via effective ligation of hydrophilic, and stimuli‐responsive polymers. Such nanomaterials are characterized via various microscopic and spectroscopic studies and exhibit their size as ≈5 nm and emission peak at ≈650 nm. Interestingly, the conjugation of thermoresponsive polymer poly(diethylene glycol monomethyl ether methacrylate) (PDEGMA) transformed the nanoconjugates AuNCs@BSA/PDEGMA as dual thermo/pH‐responsive nanomaterials.
Temporal Changes in Tick‐Borne Pathogen Prevalence in Questing Ixodes ricinus Across Different Habitats in the North‐Eastern Italian Alps
Authors: Rosso Fausta , Ferrari Giulia , Weil Tobias , Tagliapietra Valentina , Marini Giovanni , Dagostin Francesca , Arnoldi Daniele , Girardi Matteo , Rizzoli Annapaola
Published: December 2024

Changes in land use, climate, and host community are leading to increased complexity in eco‐epidemiological relationships and the emergence of zoonoses. This study investigates the changes in the prevalence of several Ixodes ricinus‐transmitted pathogens in questing ticks over a 10‐year interval (2011–2013, 2020) in natural and agricultural habitats of the Autonomous Province of Trento (North‐eastern Alps), finding an average prevalence of infection of 27.1%. Analysis of 2652 ticks, investigating four infectious agents (Borrelia burgdorferi sensu lato, Anaplasma spp., Rickettsia spp., and Babesia spp.), revealed the circulation of 11 different zoonotic pathogens, with varying infection rates across different years and habitats. In 2020, we found a decrease in Anaplasma phagocytophilum, associated with agricultural habitats, and Rickettsia spp., found in all habitats. In the same year, Babesia spp. increased in both habitats, similar to Borrelia burgdorferi sensu stricto, which was related to natural habitats. Co‐infections were identified in 8% of positive‐tested ticks with different spatiotemporal associations, primarily in natural settings. Our results provide new evidence that the risk of infection with tick‐borne pathogens in the Alpine region varies over time and in different environments, broadening the current information on co‐infection rates and the circulation of zoonotic pathogens, previously not reported in this area.
Research on marine fish classification and recognition based on an optimized ResNet50 model
Authors: Gao Guodong , Sun Zihao , Mu Guangyu , Yin Hui , Ren Yuxuan
Published: December 2024

Objective

In order to solve the problems of low accuracy and limited generalization ability in traditional marine fish species identification methods, the optimized ResNet 50 model is proposed in this paper.

Methods

First, a data set of marine fish images was constructed, targeting 30 common marine fish species (e.g., Japanese Eel Anguilla japonica, Japanese Horsehead Branchiostegus japonicus, Black Sea Sprat Clupeonella cultriventris, and Atlantic Cutlassfish Trichiurus lepturus). The marine fish images were pre-processed to increase the sample size of the data set. Second, the ResNet50 model was optimized by introducing a Dual Multi-Scale Attention Network (DMSANet) module to improve the model's attention to subtle features. A dropout regularization mechanism and dense layer were added to improve the model's generalization ability and prevent overfitting. The triplet loss function was adopted as the optimization objective of the model to reduce errors. Third, species identification was conducted on 30 species of marine fish to test the comprehensive performance of the optimized ResNet50 model.

Result

The test results showed that the optimized model had a recognition accuracy of 98.75% in complex situations, which was 3.05% higher than that of the standard ResNet50 model. A confusion matrix of the visual analysis results showed that the optimized ResNet50 model had a high accuracy rate for marine fish species recognition in many cases. To further validate and evaluate the generalization ability of the optimized ResNet50 model, partial fish data from the ImageNet database and the Queensland University of Technology (QUT) Fish Dataset were used as data sets for performance experiments. The results showed that the optimized ResNet50 model achieved accuracies of 97.65% and 98.75% on the two benchmark data sets (ImageNet and the QUT Fish Dataset, respectively).

Conclusion

The optimized ResNet50 model integrates the DMSANet module, effectively capturing subtle features in images and improving the accuracy of fish classification tasks. This model has good recognition and generalization abilities in complex scenes, and can be applied to marine fish recognition tasks in different situations.
Deep‐HH: A deep learning‐based high school student hidden hunger risk prediction system
Authors: Yang Yang , Zhang Zheng , Cao Huake , Zhang Yuchen , Wang Minao , Zhang Ning
Published: December 2024

Background

Hidden hunger (HH) refers to the deficiency of certain micronutrients. Current research suggests that approximately 70% of chronic diseases are linked to HH, which significantly affects public health. Consequently, there is an urgent need for an effective method to assess the risk of HH. This study aims to develop risk prediction models for HH using machine learning (ML).

Methods

We conducted a questionnaire survey among 9336 high school students in 11 cities within Anhui Province and assessed their HH risk using a scale. After quality control, we designated 632 students from Xuancheng City as the external test cohort and used the remaining 6477 students as the training cohort to develop predictive models. We used six ML algorithms (i.e., deep‐learning neural network [DNN], random forest, support vector machine, extreme gradient boosting, gradient boosting decision tree, and k‐nearest neighbor) to fit the training set using five‐fold cross‐validation, with hyperparameter tuning performed via Bayesian optimization. We used the “Streamlit” library to construct an online application and the “shapley additive explanations” library for model interpretability analysis.

Results

We observed that the DNN model performed best. In the external test cohort, the area under the curve reached 0.813, accuracy was 0.739, and sensitivity and specificity were 0.720 and 0.760, respectively. Furthermore, the precision‐recall curve, calibration curve, and decision curve analysis also indicated that our model had high predictive accuracy. To aid practical use, we developed an online application (http://sec.mitusml.com:9000/). Through model interpretability analysis, we discovered that the frequent consumption of fruits and coarse grains was likely to reduce the risk of HH, whereas frequently eating snacks and fried foods increased the risk of HH.

Conclusions

We developed an effective prediction model for HH and analyzed the factors that influence its risk.
Theoretical Study on Consolidation of Slurry Treated by PHDs‐VP Considering Clogging Effect and Vacuum Preloading Process
Authors: Yang Kang , Lu Mengmeng , Liu Yuanjie , Geng Xueyu , Ding Zhiwei
Published: December 2024

Prefabricated horizontal drains combined with vacuum preloading (PHDs‐VP) have addressed the shortcomings of prefabricated vertical drains combined with vacuum preloading (PVDs‐VP), beginning to emerge as a popular method for dredged slurry treatment. However, theoretical research on PHDs‐VP consolidation is relatively scarce. This study proposes a novel analytical model for predicting the consolidation behavior of the slurry treated by PHDs‐VP. This model treats the PHDs layer as a continuous drainage layer. Analytical solutions considering the clogging effect and the vacuum preloading process have been derived. The correctness and applicability of the proposed model have been verified through degeneration analysis and comparison with laboratory experimental data. Subsequently, an in‐depth sensitivity analysis of parameters has been conducted to assess the influence on consolidation. The research findings indicate that the clogging effect significantly reduces the consolidation rate, while the influence of the increasing rate in vacuum pressure is relatively minor. Additionally, increasing the slurry filling rate and the PHDs layout density can both accelerate soil consolidation. These findings offer significant guidance for the implementation of PHDs‐VP method in engineering.