bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of a novel numerical simulation to biochemical reaction systems
Authors: Sato Takashi
Published: September 2024

Recent advancements in omics and single-cell analysis highlight the necessity of numerical methods for managing the complexity of biological data. This paper introduces a simulation program for biochemical reaction systems based on the natural number simulation (NNS) method. This novel approach ensures the equitable treatment of all molecular entities, such as DNA, proteins, H2O, and hydrogen ions (H+), in biological systems. Central to NNS is its use of stoichiometric formulas, simplifying the modeling process and facilitating efficient and accurate simulations of diverse biochemical reactions. The advantage of this method is its ability to manage all molecules uniformly, ensuring a balanced representation in simulations. Detailed in Python, NNS is adept at simulating various reactions, ranging from water ionization to Michaelis–Menten kinetics and complex gene-based systems, making it an effective tool for scientific and engineering research.
Photocatalytic fluoroalkylation by ligand-to-metal charge transfer
Authors: Liu Jingyi , Cui Zhenwei , Bi Jingjing , He Xing , Ding Qingjie , Zhu Hong , Ma Chunhua
Published: September 2024

Trifluoromethyl (CF3) and other fluoroalkyl groups are of great significance in the fields of pharmaceutical chemistry and agricultural chemicals. Fluoroalkyl acids, especially trifluoroacetic acid (TFA) is considered the most ideal fluoroalkylation reagent due to its low cost and easy availability. However, the extremely high oxidation potential requirement of TFA limits its wide application. In recent years, since visible-light-induced fluoroalkylation through the ligand-to-metal charge transfer (LMCT) process can overcome the above limitations, it has become an effective synthetic tool for the construction of fluorinated compounds with complex molecules and structures. In this review, according to the classification of different metal catalysts, we summarize the trifluoromethylation and fluoroalkylation of olefins, heteroaromatics, and terminal alkynes in different metal catalytic systems and their corresponding reaction mechanisms. The photocatalytic fluoroalkylation via LMCT is believed to expedite the development of fluoro-containing drugs, and more novel fluoroalkylation methologies using this strategy will be disclosed.
Diagnostic performance of metagenomic sequencing in patients with suspected infection: a large-scale retrospective study
Authors: Li Ziyang , Tan Li , Zhang Jialiang , Long Qichen , Chen Zhiyang , Xiang Zhongyuan , Wu Weimin , Guo Zhe , Liu Huifang , Hu Bingxue , Yang Bin , Hu Min
Published: September 2024

Background

Metagenomic next-generation sequencing (mNGS) has been widely reported to identify pathogens in infectious diseases (IDs). In this work, we intended to investigate the diagnostic value and clinical acceptance of paired-samples mNGS as compared to the culture method.

Methods

A total of 361 patients with suspected infection were retrospectively included. With reference to the clinical diagnosis, we compared the diagnostic performance and clinical acceptance in pathogen detection between mNGS and culture tests. Moreover, the pathogen concordance of paired blood and respiratory tract (RT) samples in mNGS assay was investigated.

Results

Among 511 samples, 62.04% were shown to be pathogen positive by mNGS, and that for clinical diagnosis was 51.86% (265/511). When compared to culture assay (n = 428), mNGS had a significantly higher positivity rate (51.87% vs. 33.18%). With reference to the clinical diagnosis, the sensitivity of mNGS outperformed that of culture (89.08% vs. 56.72%). Importantly, mNGS exhibited a clinically accepted rate significantly superior to that of culture. In addition, the mNGS result from 53 paired blood and RT samples showed that most pairs were pathogen positive by both blood and RT, with pathogens largely being partially matched.

Conclusion

Through this large-scale study, we further illustrated that mNGS had a clinically accepted rate and sensitivity superior to those of the traditional culture method in diagnosing infections. Moreover, blood and paired RT samples mostly shared partial-matched positive pathogens, especially for pathogens with abundant read numbers in RT, indicating that both blood and RT mNGS can aid the identification of pathogens for respiratory system infection.
Quantitative study on toppling deformation zoning of antidip rock slope under different soft and hard rock conditions
Authors: Cai Junchao , Liu Jiangtao , Zhang Jie , Wang Junping , Zhang Shuo , Qi Guoqing
Published: September 2024

Toppling deformation can be classified into deep toppling (DT) and shallow toppling (ST) based on deformation mechanisms and development depth of rock mass under different soft and hard rock conditions. Currently, the toppling zoning indicators and quantitative criteria are not uniform, and human factors have a significant influence on the toppling zoning indicators. Summerizing and analyzing the existing toppling cases and toppling zoning researches, this study selects rock layer toppled angle, maximum tension within layer, unit tension within layer, and longitudinal wave velocity as indicators for toppling zoning. Considering the differences in the characteristics of deep toppling (DT) and shallow toppling (ST), the quantitative criteria for the deep and shallow toppling zoning indicators are determined respectively. This study employs the Analytic Hierarchy Process (AHP) and fuzzy comprehensive evaluation method to establish toppling zoning evaluation models. The deep toppling dam site slope at Miaowei hydropower station and the shallow toppling bank slope of Xingguang Ⅲ formation at Xiluodu Hydropower Station were tested, respectively. These results are compared with toppling zoning of field surveys to verify the rationality and applicability of the models. This achievement holds significant reference value for the toppling zoning of rock masses in engineering slopes, especially in the construction, development, and engineering management of toppling slopes.
MMC parameter selection and stability control for flexible direct transmission converter station of energy storage power station
Authors: Xiaotong Ji , Kezheng Jiang , Chenyu Wang , Chang Ye , Dan Liu
Published: September 2024

With the continuous advancement of science and technology, there is a growing global focus on new energy sources. Despite the rapid progress of offshore wind power generation systems, they are still plagued by issues such as significant transmission loss, limited transmission distance, and low-frequency oscillation, which hinder further development. To address these challenges, the Flexible Direct Current Transmission System (VSC-HVDC) has emerged as a widely studied solution. The integration of energy storage power stations presents new opportunities for enhancing offshore wind power transmission systems. These power stations not only serve as energy buffer pools to reduce transmission loss but also improve transmission efficiency through intelligent regulation and control, effectively mitigating low-frequency oscillation. This article introduces an optimization control parameter design method based on sensitivity analysis to enhance the stability of MTDC based on MMC. It outlines the topology structure of the offshore VSC-HVDC system, covering the main circuit and control system. Additionally, the article delves into the derivation of the small signal stability model of the system and investigates the selection of control parameters based on the eigenvalue objective function. Lastly, it analyzes the impact of the control system on the stability of the wind power flexible direct output converter station, highlighting the significant influence of control system parameters on the small signal stability of MTDC systems based on MMC. The MMC parameter selection strategy proposed in this paper is shown to effectively enhance system stability.
Analysis of the evolution of watershed habitat quality and its drivers under the influence of the human footprint
Authors: Jiang Yinghong , He Jing , Zhai Duanqiang , Hu Chuyan , Yu Long
Published: September 2024

Habitat quality (HQ) serves as a pivotal metric for assessing biodiversity and ecosystem health, with alterations in land use driven by human activities posing direct implications on HQ and ecological sustainability within river basins. Prior research on HQ has predominantly centered on historical land use changes, neglecting the comprehensive consideration of future land use transformations and ecological zoning strategies’ influence on HQ. Consequently, this investigation simulates potential land use shifts in the Min River Basin across various future scenarios, leveraging the integration of PLUS and InVEST models, quantitatively dissects HQ’s responsiveness to these changes and delves into the spatial differentiation dynamics underlying these responses, while also exploring the drivers behind such differentiation. Synergizing with the Human Footprint Index (HFI), the study devises a rational ecological zoning plan tailored to the region and outlines targeted control measures for each zone. The results of the study showed that: 1) the east-central part of the Min River Basin was subject to a greater degree of human interference, and the trend of interconversion between grassland, forest land, and cropland was relatively significant, with construction land mainly originating from the transfer of cropland; 2) from 2000 to 2020, average HQ scores for priority protected zones, priority recovery zones, and appropriate development zones stood at 0.9372, 0.2697, and 0.6098, respectively, accompanied by a rise in the proportion of low and moderate HQ areas to 15% and 17%; (3) DEM and Slope were the main drivers affecting HQ, and their explanatory power reached 0.519 and 0.426, respectively; (4) in comparison to a natural development scenario (ND), the planning protection scenario (PP) offers greater promise for ecological preservation and sustainable development within the Min River Basin. The research results can provide technical support for the ecological restoration of land resources and the development and protection of national land space in watershed areas.
Immune system dysfunction and inflammation in aging Shank3b mutant mice, a model of autism spectrum disorder
Authors: Cerilli Enrica , Dall’O Ginevra Matilde , Chelini Gabriele , Catena Benedetta , Weinberger Birgit , Bozzi Yuri , Pangrazzi Luca
Published: September 2024

Introduction

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental Q8 conditions characterized by deficits in social interaction/communication and restrictive/repetitive behaviors. Recent studies highlight the role of immune system dysfunction and inflammation in ASD pathophysiology. Indeed, elevated levels of pro-inflammatory cytokines were described in the brain and peripheral blood of ASD individuals. Despite this, how this pro-inflammatory profile evolves with aging and whether it may be associated with behavioral deficits is unknown. In this work, we explored the impact of aging on motor behavior and inflammation using Shank3b mutant mice, a model for syndromic ASD.

Methods

Using RT-qPCR and flow cytometry, we examined the expression of key pro-inflammatory molecules in the cerebellum, bone marrow, spleen, and peripheral blood, comparing adult and old Shank3b+/+, Shank3b+/-, and Shank3b-/- mice.

Results and discussion

Our findings revealed genotype- and age-related differences in inflammation and motor behavior, with Shank3b-/- mice exhibiting accelerated aging and motor impairments. Correlations between pro-inflammatory molecules and behavioral deficits suggest that a link may be present between systemic inflammation and ASD-related behaviors, underscoring the potential role of age-related inflammation (“inflammaging”) in exacerbating ASD symptoms.
Suppression of overactivated immunity in the early stage is the key to improve the prognosis in severe burns
Authors: Xiang Yang , Pan Bo-han , Zhang Jin , Chen Ji-qiu , Fang He , Wang Qun , Li Lin-hui , Chen Tian-sheng , Chen Jia-xin , Li Chan , Zheng Xing-feng , Zhu Shi-hui
Published: September 2024

Background

Severe burns can lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) due to inflammation-immunity dysregulation. This study aimed to identify key immune-related molecules and potential drugs for immune regulation in severe burn treatment.

Method

Microarray datasets GSE77791 and GSE37069 were analyzed to identify immune-related differentially expressed genes (DEGs), enriched pathways and prognosis-related genes. The DGIdb database was used to identify potentially clinically relevant small molecular drugs for hub DEGs. Hub DEGs were validated by total RNA from clinical blood samples through qPCR. The efficacy of drug candidates was tested in a severe burn mouse model. Pathologic staining was used to observe organ damage. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the serum IL-1b, IL-6, TNF-a and MCP-1 contents. Activation of the NF-κB inflammatory pathway was detected by western blotting. Transcriptome sequencing was used to observe inflammatory-immune responses in the lung.

Results

A total of 113 immune-related DEGs were identified, and the presence of immune overactivation was confirmed in severe burns. S100A8 was not only significantly upregulated and identified to be prognosis-related among the hub DEGs but also exhibited an increasing trend in clinical blood samples. Methotrexate, which targets S100A8, as predicted by the DGIdb, significantly reduces transcription level of S100A8 and inflammatory cytokine content in blood, organ damage (lungs, liver, spleen, and kidneys) and mortality in severely burned mice when combined with fluid resuscitation. The inflammatory-immune response was suppressed in the lungs.

Conclusion

S100A8 with high transcription level in blood is a potential biomarker for poor severe burn prognosis. It suggested that methotrexate has a potential application in severe burn immunotherapy. Besides, it should be emphasized that fluid resuscitation is necessary for the function of methotrexate.
Unmasking hemoglobin Köln: a rare cause of discrepancies between pulse oximetry and arterial oxygen saturation—a case report
Authors: Alshurafa Awni , Elsabagh Ahmed , Obaid Koutaibah Rida , Elhaji Youssef , Yassin Mohamed A.
Published: September 2024

Discrepancies between pulse oximetry and arterial oxygen saturation can pose challenges in clinical assessment. Possible underlying causes include poor peripheral perfusion, skin pigmentation, motion artifacts, and conditions like unstable hemoglobin and methemoglobinemia. Unstable hemoglobin variants, such as hemoglobin Köln, are rare inherited mutations affecting globin genes, potentially disrupting the folding, assembly, or interactions among subunits in globin molecules and the essential interactions between heme and globin for oxygen-binding properties. In this case report, we present the case of a 44-year-old Arabic woman who underwent extensive investigations due to disparities in pulse oximetry and arterial oxygen saturation, ultimately leading to the diagnosis of the unstable hemoglobin variant, hemoglobin Köln.
The vicious cycle of chronic endometriosis and depression—an immunological and physiological perspective
Authors: Sherwani Subuhi , Khan Mohd Wajid Ali , Rajendrasozhan Saravanan , Al-Motair Khalid , Husain Qayyum , Khan Wahid Ali
Published: September 2024

Endometriosis is a chronic, estrogen-dependent, proinflammatory disease that can cause various dysfunctions. The main clinical manifestations of endometriosis include chronic pelvic pain and impaired fertility. The disease is characterized by a spectrum of dysfunctions spanning hormonal signaling, inflammation, immune dysregulation, angiogenesis, neurogenic inflammation, epigenetic alterations, and tissue remodeling. Dysregulated hormonal signaling, particularly involving estrogen and progesterone, drives abnormal growth and survival of endometrial-like tissue outside the uterus. Chronic inflammation, marked by immune cell infiltration and inflammatory mediator secretion, perpetuates tissue damage and pain. Altered immune function, impaired ectopic tissue clearance, and dysregulated cytokine production contribute to immune dysregulation. Enhanced angiogenesis promotes lesion growth and survival. Epigenetic modifications influence gene expression patterns, e.g., HSD11B1 gene, affecting disease pathogenesis. Endometriosis related changes and infertility lead to depression in diagnosed women. Depression changes lifestyle and induces physiological and immunological changes. A higher rate of depression and anxiety has been reported in women diagnosed with endometriosis, unleashing physiological, clinical and immune imbalances which further accelerate chronic endometriosis or vice versa. Thus, both endometriosis and depression are concomitantly part of a vicious cycle that enhance disease complications. A multidimensional treatment strategy is needed which can cater for both endometrial disease and depression and anxiety disorders.
Role of epigenetic in cancer biology, in hematologic malignancies and in anticancer therapy
Authors: Nwabo Kamdje Armel Hervé , Dongmo Fogang Hervet Paulain , Mimche Patrice N.
Published: September 2024

Major epigenetic changes are associated with carcinogenesis, including aberrant DNA methylations and post-translational modifications of histone. Indeed evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-basedclinical and experimental studies, we hypothesize that factors associated with risk for developing a hematologic malignancy (HM), such as metabolic syndrome and chronic inflammation, may trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Signaling pathways associated with such risk factors include but are not limited to pro-inflammatory nuclear factor κB (NF-κB) and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways. The latter includes signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/mitogen-activated protein kinases (MAPKs)/extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in the biology of cancer and in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.
Behavioral, neurotransmitter and transcriptomic analyses in male and female Fmr1 KO mice
Authors: McCarthy Deirdre M. , Vied Cynthia , Trupiano Mia X. , Canekeratne Angeli J. , Wang Yuan , Schatschneider Christopher , Bhide Pradeep G.
Published: September 2024

Introduction

Fragile X syndrome is an inherited X-linked disorder associated with intellectual disabilities that begin in childhood and last a lifetime. The symptoms overlap with autism spectrum disorder, and the syndrome predominantly affects males. Consequently, FXS research tends to favor analysis of social behaviors in males, leaving a gap in our understanding of other behavioral traits, especially in females.

Methods

We used a mouse model of FXS to analyze developmental, behavioral, neurochemical, and transcriptomic profiles in males and females.

Results

Our behavioral assays demonstrated locomotor hyperactivity, motor impulsivity, increased “approach” behavior in an approach-avoidance assay, and deficits in nest building behavior. Analysis of brain neurotransmitter content revealed deficits in striatal GABA, glutamate, and serotonin content. RNA sequencing of the ventral striatum unveiled expression changes associated with neurotransmission as well as motivation and substance use pathways. Sex differences were identified in nest building behavior, striatal neurotransmitter content, and ventral striatal gene expression.

Discussion

In summary, our study identified sex differences in specific behavioral, neurotransmitter, and gene expression phenotypes and gene set enrichment analysis identified significant enrichment of pathways associated with motivation and drug reward.
Memory-efficient neurons and synapses for spike-timing-dependent-plasticity in large-scale spiking networks
Authors: Urbizagastegui Pablo , van Schaik André , Wang Runchun
Published: September 2024

This paper addresses the challenges posed by frequent memory access during simulations of large-scale spiking neural networks involving synaptic plasticity. We focus on the memory accesses performed during a common synaptic plasticity rule since this can be a significant factor limiting the efficiency of the simulations. We propose neuron models that are represented by only three state variables, which are engineered to enforce the appropriate neuronal dynamics. Additionally, memory retrieval is executed solely by fetching postsynaptic variables, promoting a contiguous memory storage and leveraging the capabilities of burst mode operations to reduce the overhead associated with each access. Different plasticity rules could be implemented despite the adopted simplifications, each leading to a distinct synaptic weight distribution (i.e., unimodal and bimodal). Moreover, our method requires fewer average memory accesses compared to a naive approach. We argue that the strategy described can speed up memory transactions and reduce latencies while maintaining a small memory footprint.
Glymphatic system dysfunction associated with cognitive impairment in chronic tinnitus patients
Authors: Du Yinjuan , Huang Zhichun , Wu Yuanqing , Xue Yuan , Che Zigang
Published: September 2024

Background

The glymphatic system has been regarded as a pivotal factor in the pathogenesis of neurodegenerative diseases. Given the heightened risk of cognitive impairment in chronic tinnitus patients, the possible alterations of the glymphatic system in tinnitus patients remain elusive. This study was designed to evaluate glymphatic dysfunction in chronic tinnitus patients using the diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) approach.

Methods

Fifty chronic tinnitus patients and 50 age, sex, and education-matched healthy controls (HCs) with normal hearing thresholds were recruited. The DTI-ALPS was calculated from each group. We investigated the differences in the DTI-ALPS index between the tinnitus patients and HCs. The relationships between the DTI-ALPS index and specific cognitive performance were further assessed.

Results

There were significant differences in the DTI-ALPS index between the two groups. The DTI-ALPS index was significantly lower in the tinnitus group than in HCs group (p < 0.01). In addition, the Dyyproj index was significantly higher in the tinnitus group than in the HC group (p < 0.01). In chronic tinnitus patients, the decreased DTI-ALPS index was negatively associated with worse TMT-B scores (r = −0.309, p = 0.039). Moreover, the increased Dyyproj index was negatively correlated with the reduced AVLT performances (r = −0.413, p = 0.005).

Conclusion

In this current study, glymphatic system activity in chronic tinnitus was investigated for the first time using DTI-ALPS index. Significant decrease in glymphatic system function was detected in chronic tinnitus, which correlated well with the specific cognitive performance. The current study may provide pivotal imaging markers for chronic tinnitus with cognitive impairment.
Longitudinal evaluation of structural brain alterations in two established mouse models of Gulf War Illness
Authors: Carpenter Jessica M. , Hughes Sarah N. , Filipov Nikolay M.
Published: September 2024

Gulf War Illness (GWI) affects nearly 30% of veterans from the 1990–1991 Gulf War (GW) and is a multi-symptom illness with many neurological effects attributed to in-theater wartime chemical overexposures. Brain-focused studies have revealed persistent structural and functional alterations in veterans with GWI, including reduced volumes, connectivity, and signaling that correlate with poor cognitive and motor performance. GWI symptomology components have been recapitulated in rodent models as behavioral, neurochemical, and neuroinflammatory aberrations. However, preclinical structural imaging studies remain limited. This study aimed to characterize the progression of brain structural alterations over the course of 12 months in two established preclinical models of GWI. In the PB/PM model, male C57BL/6 J mice (8–9 weeks) received daily exposure to the nerve agent prophylactic pyridostigmine bromide (PB) and the pyrethroid insecticide permethrin (PM) for 10 days. In the PB/DEET/CORT/DFP model, mice received daily exposure to PB and the insect repellent DEET (days 1–14) and corticosterone (CORT; days 7–14). On day 15, mice received a single injection of the sarin surrogate diisopropylfluorophosphate (DFP). Using a Varian 7 T Bore MRI System, structural (sagittal T2-weighted) scans were performed at 6-, 9-, and 12-months post GWI exposures. Regions of interest, including total brain, ventricles, cortex, hippocampus, cerebellum, and brainstem were delineated in the open source Aedes Toolbox in MATLAB, followed by brain volumetric and cortical thickness analyses in ImageJ. Limited behavioral testing 1 month after the last MRI was also performed. The results of this study compare similarities and distinctions between these exposure paradigms and aid in the understanding of GWI pathogenesis. Major similarities among the models include relative ventricular enlargement and reductions in hippocampal volumes with age. Key differences in the PB/DEET/CORT/DFP model included reduced brainstem volumes and an early and persistent loss of total brain volume, while the PB/PM model produced reductions in cortical thickness with age. Behaviorally, at 13 months, motor function was largely preserved in both models. However, the GWI mice in the PB/DEET/CORT/DFP model exhibited an elevation in anxiety-like behavior.
Evaluation of urinary C-reactive protein as an early detection biomarker for pancreatic ductal adenocarcinoma
Authors: Ali Nurshad , Debernardi Silvana , Kurotova Evelyn , Tajbakhsh Jian , Gupta Nirdesh K. , Pandol Stephen J. , Wilson Patrick , Pereira Stephen P. , Greenhalf Bill , Blyuss Oleg , Crnogorac-Jurcevic Tatjana
Published: September 2024

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. Up to now, no specific screening or diagnostic tests are available for early PDAC detection. As a result, most patients are diagnosed with advanced or metastatic disease, which leads to a poor prognosis. In this study, we aimed to evaluate the diagnostic value of urinary CRP (uCRP) alone and in combination with our previously established urine biomarker panel (REG1B, LYVE1 and TFF1) for early detection of PDAC. A total of 534 urine samples from multiple centres were analysed: 93 from healthy individuals, 265 from patients with benign hepatobiliary diseases and 176 from PDAC patients. The uCRP and the urinary biomarker panel were assessed using commercial ELISA assays, while plasma CA19-9 and blood CRP (bCRP) were measured using Roche Cobas platform. Multiple logistic regression and nonparametric Kruskal–Wallis test were used for statistical analysis. An internal validation approach was applied, and the validated AUC estimators were reported to ensure accuracy. A significant difference was observed in the medians of uCRP between healthy and benign controls and PDAC sample groups (p < 0.001). uCRP levels were not dependent on gender and age, as well as cancer stage. When uCRP was combined with the urinary biomarker panel, it achieved AUCs of 0.878 (95% CI: 0.802-0.931), 0.798 (95% CI: 0.738-0.859) and 0.813 (95% CI: 0.758-0.869) in healthy vs PDAC, benign vs PDAC and healthy and benign vs PDAC sample groups, respectively. However, adding plasma CA19-9 to the urinary biomarker panel yielded a better performance, with AUCs of 0.978 (95% CI: 0.959-0.996), 0.911 (95% CI: 0.873-0.949) and 0.919 (95% CI: 0.883-0.955) in the healthy vs PDAC, benign vs PDAC and healthy and benign vs PDAC comparisons, respectively. In conclusion, we show that measuring CRP in urine is a feasible analytical method, and that uCRP could potentially be a promising biomarker in various diseases including other cancer types.
Recent clinical evidence on nutrition, novel pharmacotherapy, and vaccination in inflammatory bowel diseases
Authors: Gheonea Theodora , Bogdan Maria , Meca Andreea-Daniela , Rogoveanu Ion , Oancea Carmen
Published: September 2024

Inflammatory bowel diseases (IBD), which enclose Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory ailments. Their specific pathogenesis is not completely clarified, the worldwide incidence and prevalence of IBD has been steadily growing, and there is still not a definitive cure. The management of IBD has become more and more targeted, with specific immune mediators identified to be involved in its pathogenesis. Vedolizumab, a humanised monoclonal antibody binding specifically to the α4β7 integrin, is a gut-selective immunosuppressive biologic drug administered for both CD and UC. With the same indications as vedolizumab, ustekinumab is a fully human IgG1κ monoclonal antibody binding with specificity to the shared p40 protein subunit of human cytokines interleukin (IL)-12 and IL-23. Several selective IL-23p19 monoclonal antibodies (risankizumab, mirikizumab, and guselkumab) have also revealed admirable efficacy and safety in IBD patients. Nutrition is a very important environmental factor associated with the onset and progression of IBD, and the Western diet is considered to contribute to the development of IBD. In this narrative review, our aim is to present an overview of the main results from recent clinical studies on IBD regarding diet, new drug treatments, and also vaccination.
Exploring pharmacokinetic variability of palbociclib in HR+/HER2- metastatic breast cancer: a focus on age, renal function, and drug–gene interactions
Authors: Peruzzi Elena , Posocco Bianca , Gerratana Lorenzo , Nuti Margherita , Orleni Marco , Gagno Sara , De Mattia Elena , Puglisi Fabio , Cecchin Erika , Toffoli Giuseppe , Roncato Rossana
Published: September 2024

Palbociclib, an oral inhibitor of cyclin-dependent kinase 4 and 6, is approved for the treatment of metastatic breast cancer. This study investigated the influence of diverse clinical and biological factors—age, renal function, genetic variations, and concomitant medications (pharmacokinetic covariates)—on palbociclib pharmacokinetics. Employing a validated LC-MS/MS method, we analyzed the minimum plasma concentrations (Ctrough) of palbociclib in 68 women and determined the percentage deviations from the median Ctrough for each dosage group. Variations in a panel of absorption, distribution, metabolism, and excretion (ADME) genes were assessed using end-point allele-specific fluorescence detection and pyrosequencing. Two distinct patient cohorts were defined based on median values of age, creatinine, and eGFR, which exhibited statistically significant differences in percentage deviations (p = 0.0095, p = 0.0288, and p = 0.0005, respectively). Homozygous carriers of the PPARA variants displayed larger positive percentage deviations than the other group (p = 0.0292). Similarly, patients concurrently taking CYP3A and P-glycoprotein inhibitors alongside anticancer therapy exhibited significant variations (p = 0.0285 and p = 0.0334, respectively). Furthermore, exploring the drug–drug–gene interactions between inhibitors of CYP3A and P-glycoprotein with their respective genetic variants revealed two patient groups with statistically different percentage deviations (p = 0.0075, p = 0.0012, and p = 0.0191, respectively). These results could help address cases where pharmacokinetic covariates or subclinical conditions impair palbociclib adherence or response, aiming to offer tailored dosing strategies or monitoring for individual patients.
Effects of intermittent seating upright, lower body negative pressure, and exercise on functional tasks performance after head-down tilt bed rest
Authors: Clément Gilles , Moudy Sarah C. , Macaulay Timothy R. , Mulder Edwin , Wood Scott J.
Published: September 2024

Introduction

Bed rest can be used as a ground-based analog of the body unloading associated with spaceflight. In this study, we determined how strict head-down tilt bed rest affects subjects’ performance of functional tests (sit-to-stand, tandem walk, walk-and-turn, dynamic posturography) that challenge astronauts’ balance control systems immediately after they return from space.

Methods

Forty-seven participants were assessed before and a few hours after 30 days of 6° head down tilt bed rest at the DLR:envihab facility. During this bed rest study, called SANS-CM, the participants were divided into 4 groups that either a) were positioned in head-down tilt continuously throughout the 30 days; b) sat upright for 6 h a day; c) were exposed to lower body negative pressure (LBNP) for 6 h a day; or d) exercised for 60 min and then wore venous-occlusive cuffs for 6 h a day.

Results

Results showed that strict head-down tilt bed rest caused deficits in performance of functional tasks that were similar to those observed in astronauts after spaceflight. Seated upright posture mitigated these deficits, whereas exercise or LBNP and cuffs partly mitigated them.

Discussion

These data suggest that more direct, active sensorimotor-based countermeasures may be necessary to maintain preflight levels of functional performance after a long period of body unloading.
Validation of the French version of the Body Awareness Questionnaire: toward a way to assess alexisomia
Authors: Carre Arnaud , Shankland Rebecca , Guillaume Philippe , Duclos Jeanne , El-Jor Claire , Pellissier Sonia , Flaudias Valentin
Published: September 2024

Background

Awareness of one's own states is a particularly important part of cognition and emotion regulation. Recently, the concept of alexisomia has been used to refer to lack of awareness and expression of somatic sensations. Developing self-reported questionnaires to evaluate alexisomia represents a challenge for clinical psychology and medicine. In this context, we suggested to adapt the Body Awareness Questionnaire in French to measure alexisomia and its relation to alexithymia. In fact, we carried out a backtranslation and studied the validity of the construct in relation to proximal constructs around emotional awareness.

Methods

For this study, 610 university students completed questionnaires measuring a three dimensions alexithymia concept [with The Toronto Alexithymia Scale (TAS-20)] or the five dimensions alexithymia concept [with The Bermond-Vorts Alexithymia Questionnaire (BVAQ-B)] and alexisomia (with the BAQ).

Results

Confirmatory factor analyses showed that the BAQ can be envisaged through 4 factors as well as a unidimensional model to refer to alexisomia. We also found that body awareness was negatively related to scores of alexithymia.

Conclusion

Results are discussed in light of the construct of alexisomia and its clinical implications in somatic as well as mental disorders. We suggest that the BAQ, which assesses interoception, can contribute, in part, to the assessment of alexisomia. Like alexithymia, this is a key concept to take into consideration when designing treatment and prevention programs.
Community and family relationships across the transition to medical school: links to student adjustment
Authors: Rincon Brenda , Bravo Diamond Y. , Arnold Elisha , Meza Alexis , Camacho-Thompson Daisy
Published: September 2024

Introduction

Supporting students during the transition to medical school is crucial for their academic adjustment. However, there has been limited research on the protective role of community and family support during this transition, despite evidence of the benefits of supportive relationships in higher education. Guided by self-determination theory, the current cross-sectional study explored how changes in family and community relationships impact Cuban medical students' sense of belonging in their field and their grade expectations.

Methods

A total of 881 medical students (MAge = 21.51, SD= 2.23, range = 18–33; 54% female; 72.2% Cuban) participated in this study. Participants included students across 6 years of medical school (1st year = 14.8%, 2nd year = 10%, 3rd year = 24.1%, 4th year = 19.3%, 5th year = 11.8%, 6th year = 20%).

Results

Controlling for key demographics (e.g., student aid experience, family legacy, nationality, year in medical school, prior academic performance, gender, and offspring), our findings revealed that improvements in community relationships—rather than family relationships—were associated with higher levels of field belonging. Additionally, more extensive experience as a student aid and a greater number of family members with a medical background were linked to higher levels of field belonging and higher grade expectations. Notably, higher prior academic performance was associated with increased field belonging but did not affect grade expectations. Conversely, identifying as female was related to both higher field belonging and higher grade expectations.

Discussion

Our study highlights the importance of supportive community relationships for medical students' academic adjustment. We discuss the potential benefits of enhancing community relationships within medical school training programs.
The moderating role of food cravings in the relationship between weight suppression and eating disorder psychopathology in college students
Authors: Garcia Susana Cruz , Hormes Julia M.
Published: September 2024

Weight suppression (WS), the difference between an individual’s current and highest adult weight, is predictive of eating-related pathology across diagnostic categories and poor eating disorder treatment outcomes, but findings from non-clinical samples have been mixed. Cravings are strong urges for specific foods that are subjectively difficult to resist. Food cravings are now widely conceptualized as cognitive-affective states characterized by intrusive thoughts that are perceived as distressing and can interfere with adaptive functioning. Food cravings are known antecedents of binge eating, but little is known about how they interact with WS. We examined the obsessive-compulsive aspects of food cravings as potential moderators of the association between WS and eating disorder symptoms in general, and binge eating specifically in a cross-sectional study of college students. Participants (n = 144, 60.4% female) self-reported their height and current and past highest adult weight and completed the Binge Eating Scale (BES), Eating Disorder Examination-Questionnaire (EDE-Q), and Obsessive Compulsive Eating Scale (OCES). Main and interactive effects of WS and OCES scores on EDE-Q global and BES scores were examined in regression models. There were significant main effects of OCES scores on overall eating disorder symptom severity as well as binge frequency, with those endorsing more craving-related intrusive thoughts and compulsive urges engaging in maladaptive behaviors more frequently. WS alone did not consistently cross-sectionally predict eating disorder psychopathology. Findings suggest that food cravings are significantly associated with disordered eating symptoms and specifically binge eating frequency and should be accounted for in future research on WS in clinical and non-clinical samples.
Embodiment and agency in a digital world
Authors: Gangopadhyay Nivedita , Pichler Alois
Published: September 2024

We are agents and our agency is often best characterized in terms of embodied cognition. However, this is not to deny that there are cognitively significant ways of agentive engagement with the world that may be described without referring to our embodiment. In this paper we shall focus on the interplay between embodied agency and non-embodied agency or agency that may not be straightforwardly described in terms of embodied cognition in the context of interaction with digital technologies. In recent years a lot of our daily lives are coupled to the world via digital technologies. Yet how to understand the nature and evolution of our agency in the context of interacting with daily digital technologies is an open question. We propose to address this question by focusing on whether the steady development of digital technologies in our daily lives challenges the view that embodied agency is the de facto way of robustly engaging with the world and if embodied cognition is challenged then what is taking its place in scenarios where it was once dominant.
Effect of music therapy on anxiety in full-term pregnant women
Authors: Ji Chao , Li Juan , Nie Qiaole , Wang Shuo
Published: September 2024

Objectives

To examine the impact of receptive music therapy on maternal anxiety both during and after the process of childbirth.

Methods

In this experimental study, 217 women were divided into the receptive music therapy and control groups. The first group were exposed to music at intervals of 20 minutes for a duration of 30 minutes during labor. Data were collected using the Pregnant Information Form, the State Anxiety Inventory (STAI), Visual Analogue Scale and Edinburgh postnatal depression scale.

Results

The pregnant women who participated in the music group exhibited reduced scores of STAI, both during the active time (46.42 ± 11.69 vs. 50.21 ± 11.14, 44.37 ± 10.38 vs. 47.56 ± 11.46, P<0.05) and two hours after giving birth(26.32 ± 6.23 vs. 29.55 ± 8.9, 30.38 ± 7.15 vs. 33.08 ± 9.45, P<0.05). At the first stage of labor, pregnant women in the music group experienced dramatically reduced score of pain in active phase (6.39 ± 1.00 vs. 6.91 ± 0.99, P<0.05) and Edinburgh postnatal depression scale at discharged from the hospital (6.68 ± 3.36 vs. 7.66 ± 3.54, P<0.05).

Conclusion

Receptive music therapy is effective in reducing pain during labor and anxiety during prenatal and postnatal periods. The use of receptive music therapy in obstetric care can be an effective tool in preventing anxiety-induced complications.
Regional differences, dynamic evolution, and influencing factors of high-quality medical resources in China’s ethnic minority areas
Authors: Liang Binghua , Huang Lifeng , Chen Zhuo , Hao Bangyan , Li Chengcheng
Published: September 2024

Background

In China, as people’s standard of living improves and the medical service system becomes more sophisticated, the demand for higher-quality and improved healthcare services is steadily rising. Inequality in health resource allocation (HRA) is more pronounced in ethnic minority areas (EMAs) than in developed regions. However, little research exists on high-quality medical resources (HQMRs) in China’s EMAs. Hence, we examined the spatiotemporal dynamic evolution of HQMRs in China’s EMAs from 2007 to 2021 and identified the main factors affecting their respective HQMR levels.

Methods

We selected tertiary hospitals to represent the quality of healthcare resources. We employed descriptive statistical techniques to analyze changes in the distribution of HQMRs from 2007 to 2021. We used the Dagum Gini coefficient and kernel density approach to analyze the dynamic evolution of HQMRs in China’s EMAs. We utilized the least squares dummy variable coefficient (LSDVC) to identify key factors affecting HQMR.

Results

The number of HQMRs in each EMA has risen annually. The average number of tertiary hospitals increased from 175 in 2007 to 488 in 2021. The results of the Dagum Gini coefficient revealed that the differences in the HQMR level in China’s EMAs have slowly declined, and intra-regional disparities have now become the primary determining factor influencing overall variations. The kernel density plot indicated that the HQMR level improved significantly during the study period, but bifurcation became increasingly severe. Using the LSDVC for analysis, we found that gross domestic product (GDP) per capita, the size of the resident population, and the number of students enrolled in general higher education exhibited a significant negative correlation with HQMR levels, while GDP and urbanization rate had a significant promoting effect.

Conclusion

The HQMR level in EMAs has risen rapidly but remains inadequate. The differences in HQMR between regions have continued to narrow, but serious bifurcation has occurred. Policymakers should consider economic growth, education, and population size rather than simply increasing the number of HQMRs everywhere.
Eco-friendly bio-composite sheets: a study on the utilization of banana peels, cassava starch, and banana stem fibers
Authors: Ishara G.K.K , Koliyabandara Pabasari A , Samarakoon Gamunu
Published: September 2024

Massively using conventional plastics has led to significant environmental issues, including harm to ecosystems, wildlife, and human health, contributions to greenhouse gas emissions, and resource depletion through their extraction and production. Thus, there is an urgent imperative to seek sustainable alternatives like bio-composites. This research established the viability of banana peels and cassava starch for eco-friendly bio-composite sheets, offering insights into their properties and performance The bio-composite materials, composed of banana peels, cassava starch, banana stem fiber, glycerol, and acetic acid, were prepared in different weight-based proportions. The preparation process involved cleaning, drying, blending, and molding the materials to produce consistent bio-composite samples. The properties and performance of the composite samples were assessed for water absorption, moisture content, and tensile strength. Notably, the combination of banana peels and cassava in a 1:2 ratio, along with banana stem fiber, demonstrated favorable attributes, including reduced water absorption (ranging from 6.42 to 30.91%), desirable moisture content (ranging from 8.06 to 11.27%), and increased tensile strength (ranging from 5.345 to 11.892 MPa). These findings confirm the viability of using banana peels and cassava starch in producing bio-composite sheets, offering a sustainable alternative to conventional plastics. This study contributes to the field of sustainable materials by providing insights into the properties and performance of bio-composites, thereby supporting the development of eco-friendly bio-composite sheets.