bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies
Authors: Uchiyama Makoto , Mishima Kazuo , Yagi Tomoko , Yoshihara Tatsuya , Eto Takashi , Muehlan Clemens , Togo Osamu , Inoue Yuichi 
Published: August 2024

SummaryDaridorexant is a dual orexin receptor antagonist for the treatment of insomnia. We report results from the first two randomised, double‐blind clinical studies of daridorexant in Japanese subjects. In the Phase 1 study, daridorexant (10, 25, 50 mg) or placebo were administered in the morning for 4 days in 24 young (mean age 26.9 years) and 24 older (mean age 69.7 years) healthy Japanese adults. Daridorexant reached a peak plasma concentration within 1.0 h across every dose and age group. For all doses, the mean plasma concentration of daridorexant showed a similar change between the age groups. Exposure parameters increased dose‐dependently with minimal/no accumulation upon repeated dosing. The terminal half‐life was ~8 h. In the Phase 2, four‐period, four‐way crossover study, 47 Japanese subjects (mean age 50.4 years) with insomnia disorder were randomised to receive four treatments (daridorexant 10, 25, 50 mg, placebo) during four treatment periods, each consisting of two treatment nights (5–12 day washout between treatment periods). Subjects continued their fourth treatment for 12 further days. A statistically significant dose–response relationship (multiple‐comparison procedure‐modelling, p < 0.0001) was found in the reduction of polysomnography‐measured wake after sleep onset (WASO; primary endpoint) and latency to persistent sleep (secondary endpoint) from baseline to days 1/2. Statistically significant dose–response relationships were also observed for secondary subjective endpoints from baseline to days 1/2 (sWASO, latency to sleep onset). All daridorexant doses were well tolerated, with no treatment discontinuations and no next‐morning residual effects. These results supported further investigation of daridorexant in Japanese patients with insomnia disorder.
A ribonuclease T2 protein FocRnt2 contributes to the virulence of Fusarium oxysporum f. sp. cubense tropical race 4
Authors: He Yanqiu , Li Pengfei , Zhou Xiaoshu , Ali Shaukat , Zhu Jie , Ma Yini , Li Jieling , Zhang Nan , Li Huaping , Li Yunfeng , Nie Yanfang 
Published: August 2024

AbstractBanana Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), is a major disease of banana plants worldwide. Effector proteins play critical roles in banana–Foc TR4 interaction. Our previous studies highlighted a ribonuclease protein belonging to the T2 family (named as FocRnt2) in the Foc TR4 secretome, which was predicted to be an effector. However, its biological function in Foc TR4 infection is still unclear. Herein, we observed significant expression of FocRnt2 during the early stage of fungal infection in planta. A yeast signal sequence trap assay showed that FocRnt2 contained a functional signal peptide for secretion. FocRnt2 possessed ribonuclease activity that could degrade the banana total RNA in vitro. Subcellular localization showed that FocRnt2 was localized in the nucleus and cytoplasm of Nicotiana benthamiana leaves. Transient expression of FocRnt2 suppressed the expression of salicylic acid‐ and jasmonic acid‐signalling marker genes, reactive oxygen species accumulation, and BAX‐mediated cell death in N. benthamiana. FocRnt2 deletion limited fungal penetration, reduced fusaric acid biosynthesis in Foc TR4, and attenuated fungal virulence against banana plants, but had little effect on Foc TR4 growth and sensitivity to various stresses. Furthermore, FocRnt2 deletion mutants induced higher expression of the defence‐related genes in banana plants. These results suggest that FocRnt2 plays an important role in full virulence of Foc TR4, further improving our understanding of effector‐mediated Foc TR4 pathogenesis.
The molecular mechanisms that underlie IGHMBP2‐related diseases
Authors: Rzepnikowska Weronika , Kaminska Joanna , Kochański Andrzej 
Published: August 2024

AbstractImmunoglobulin Mu‐binding protein 2 (IGHMBP2) pathogenic variants result in the fatal, neurodegenerative disease spinal muscular atrophy with respiratory distress type 1 (SMARD1) and the milder, Charcot–Marie‐Tooth (CMT) type 2S (CMT2S) neuropathy. More than 20 years after the link between IGHMBP2 and SMARD1 was revealed, and 10 years after the discovery of the association between IGHMBP2 and CMT2S, the pathogenic mechanism of these diseases is still not well defined. The discovery that IGHMBP2 functions as an RNA/DNA helicase was an important step, but it did not reveal the pathogenic mechanism. Helicases are enzymes that use ATP hydrolysis to catalyse the separation of nucleic acid strands. They are involved in numerous cellular processes, including DNA repair and transcription; RNA splicing, transport, editing and degradation; ribosome biogenesis; translation; telomere maintenance; and homologous recombination. IGHMBP2 appears to be a multifunctional factor involved in several cellular processes that regulate gene expression. It is difficult to determine which processes, when dysregulated, lead to pathology. Here, we summarise our current knowledge of the clinical presentation of IGHMBP2‐related diseases. We also overview the available models, including yeast, mice and cells, which are used to study the function of IGHMBP2 and the pathogenesis of the related diseases. Further, we discuss the structure of the IGHMBP2 protein and its postulated roles in cellular functioning. Finally, we present potential anomalies that may result in the neurodegeneration observed in IGHMBP2‐related disease and highlight the most prominent ones.
Delirium care burden of intensive care nurses caring for patients undergoing open‐heart surgery: A mixed‐method research
Authors: Ulus Meltem , Durmaz Edeer Aylin 
Published: August 2024

AbstractBackgroundDelirium is an acute confusional state characterized by inattention, cognitive dysfunction and an altered level of consciousness. Delirium causes negative outcomes in patients, and patients with delirium increase the workload of nurses. Therefore, it is important to recognize the challenges and burdens experienced by nurses caring for patients with delirium.AimTo determine the subjective burden experienced by intensive care nurses caring for patients who have undergone open‐heart surgery.Study DesignA mixed‐method sequential explanatory design. A non‐probability purposive sampling method was used for the quantitative stage. Using OpenEpi, we employed the method of sample calculation with an unknown universe. The sample size of the quantitive study comprised 130 nurses. Quantitative data were collected with Google survey. For gathering qualitative data, online video interviews were conducted with 10 nurses, an interpretive phenomenological approach was used and content analysis was performed.ResultsIn the quantitative phase, we found that the subjective burden was high. In the qualitative phase, five main themes emerged: difficulty in recognizing delirium, physical burden, emotional burden, burden in care management of patients with delirium and the effect of patients with delirium on other patients. The nurses experienced physical and emotional burden in delirium management and felt lonely while caring for patients with delirium.ConclusionsBecause nurses play a key role in the care of patients with delirium, reducing the burden nurses experience when caring for patients with delirium should be considered important in ensuring that this patient population receives adequate care.Relevance to Clinical PracticeDelirium patients create a care burden for intensive care nurses. To reduce this burden of care, in‐service training in patient management and bedside teaching support should be provided to nurses. Furthermore, the use of a valid scale to diagnose delirium should be integrated into health policies. Nurses should not be left alone in the management of delirium. Managing delirium patients with a team including physicians, nurses and professionals from other health disciplines will ensure that patients receive high‐quality care, thereby reducing the care burden of nurses.
Autonomic assessment at the intersection of psychosocial and gastrointestinal health
Authors: Kolacz Jacek 
Published: August 2024

AbstractBackgroundWearable technology is increasingly used in clinical practice and research to monitor functional gastrointestinal symptoms and mental health.AimsThis article explores the potential of wearable sensors to enhance the understanding of the autonomic nervous system (ANS), particularly its role in linking psychological and gastrointestinal function. The ANS, facilitates brain‐gut communication and is responsive to psychosocial conditions. It is implicated in disorders related to psychological stress and gut‐brain interaction. Wearable technology enables tracking of the ANS in daily life, offering complementary and alternative methods from traditional lab‐based measures. This review places focus on autonomic metrics such as respiratory sinus arrhythmia, vagal efficiency, and electrodermal activity as well as self‐reports of autonomic symptoms.DiscussionPotential applications include use of wearable sensors for tracking autonomic activity in disorder of gut‐brain interaction such as cyclic vomiting syndrome, in which ANS dysregulation may be triggered by psychosocial factors. Considerations for data interpretation and contextualization are addressed, acknowledging challenges such as situational confounders of ANS activity and accuracy of wearable devices.
Unsupervised machine learning highlights the challenges of subtyping disorders of gut‐brain interaction
Authors: Dowrick Jarrah M. , Roy Nicole C. , Bayer Simone , Frampton Chris M. A. , Talley Nicholas J. , Gearry Richard B. , Angeli‐Gordon Timothy R. 
Published: August 2024

AbstractBackgroundUnsupervised machine learning describes a collection of powerful techniques that seek to identify hidden patterns in unlabeled data. These techniques can be broadly categorized into dimension reduction, which transforms and combines the original set of measurements to simplify data, and cluster analysis, which seeks to group subjects based on some measure of similarity. Unsupervised machine learning can be used to explore alternative subtyping of disorders of gut‐brain interaction (DGBI) compared to the existing gastrointestinal symptom‐based definitions of Rome IV.PurposeThis present review aims to familiarize the reader with fundamental concepts of unsupervised machine learning using accessible definitions and provide a critical summary of their application to the evaluation of DGBI subtyping. By considering the overlap between Rome IV clinical definitions and identified clusters, along with clinical and physiological insights, this paper speculates on the possible implications for DGBI. Also considered are algorithmic developments in the unsupervised machine learning community that may help leverage increasingly available omics data to explore biologically informed definitions. Unsupervised machine learning challenges the modern subtyping of DGBI and, with the necessary clinical validation, has the potential to enhance future iterations of the Rome criteria to identify more homogeneous, diagnosable, and treatable patient populations.
Tourniquet Effect on Patients Undergoing Total Knee Arthroplasty: A Single‐Blind, Randomized Controlled Trial
Authors: Dong Ziyang , Li Yang , Xue Heng , Tao Liyuan , Tian Hua 
Published: August 2024

BackgroundTourniquet is applied in Total Knee Arthroplasty (TKA) to reduce intraoperative blood loss and improve view of surgical field. However, tourniquet use in TKA is still in dispute. Some researchers find that tourniquet may lead to extra side effects such as aggravated pain and limb swelling, while others consider that tourniquet has no significant adverse impact on clinical outcomes of TKA patients. This trial is conducted to evaluate tourniquet effect on TKA patients.MethodsA prospective, single‐blind, randomized controlled trail is adopted with a sample size of 130 knees from August 2020 to February 2023. Patients undergoing TKA are randomly allocated to tourniquet group and non‐tourniquet group. Outcomes including quadriceps thickness and stiffness, operation time, total blood loss, intraoperative blood loss, postoperative blood loss, transfusion rate, thigh circumference, knee and thigh VAS, D‐Dimer and CRP level, knee function score, patient satisfaction, and complications are evaluated in this trial. Student's t‐test, Mann–Whitney U test, Pearson's chi‐square test, and Fisher's exact test are used in this study.ResultsNo significant difference in demographic information and baseline outcomes were found (p > 0.05). Participants in the tourniquet group had significantly less total blood loss and intraoperative blood loss, more postoperative blood loss, and higher D‐Dimer level on postoperative day 3 when compared with non‐tourniquet group (p < 0.05). Other outcomes including quadriceps thickness and stiffness, operation time, postoperative blood loss, transfusion rate, thigh circumference, knee and thigh VAS, D‐Dimer level on postoperative day 1, CRP level, knee function score, patient satisfaction, and complications showed no significant difference (p > 0.05).ConclusionTourniquet application can effectively reduce intraoperative blood loss and total blood loss, without significant side effects. Hence, we advocate the regular use of tourniquet in primary TKA.
Age‐related Differences in Volumetric Bone Mineral Density, Structure, and Bone Strength of Surgical Neck of Humerus in Postmenopausal Women
Authors: Wang Yeming , Li Jian , Men Yutao , Wei Wanfu 
Published: August 2024

ObjectivePostmenopausal changes in bone mass and structure compromise the mechanical properties of proximal humerus, predisposing it to low‐energy fractures with complex morphology. The aim of the study is to investigate associations of bone quality and estimated bone strength of the surgical neck with age after menopause.MethodsA total of 122 healthy postmenopausal women were recruited from December 2016 to December 2022 and assigned to three groups: the 50–59 years group, the 60–69 years group, and the older than 70 years group. Bone properties of the surgical neck, including volumetric bone mineral density (vBMD), cortical thickness (CTh), the periosteal and medullary size, and estimated indices of bone strength were evaluated by quantitative computed tomography.ResultsCompared to the 50–59 years group, postmenopausal women aged over 70 years were characterized by lower cortical thickness (13.9%) and vBMD (6.65%), as well as reduced strength indices including the minimum and maximum section modulus (Zmin 18.11%, Zmax 21.71%), polar section modulus (Zpol 20.21%), and the minimum and maximum second moments of area (Imax 21.01%, Imin 21.43%). Meanwhile, the difference in periosteal diameter and perimeter, total area in three groups did not reach statistical significance. Both cortical thickness and vBMD value were inversely associated with age, showing 10.56% and 23.92% decline. Imax showed the greatest age‐related decrease between age of 54 and 86 years (39.08%), followed by Zmax (−35.77%), Imin (−35.73%), Zpol (−34.90%) and Imin (−23.92%).The strength indices had stronger correlations with cortical thickness than with bone size or density.ConclusionIn postmenopausal women, aging is associated with a significant decline in cortical bone thickness and mechanical strength of the proximal humerus, especially over the age of 70 years.
Biomechanical Effects of Multi‐segment Fixation on Lumbar Spine and Sacroiliac Joints: A Finite Element Analysis
Authors: Zhao Geng , Wang Lianlei , Wang Hongwei , Li Chao , Yuan Suomao , Sun Junyuan , Tian Yonghao , Liu Xinyu 
Published: August 2024

ObjectiveSpine fixation surgery affects the biomechanical environment in the sacroiliac joint (SIJ), which may lead to the SIJ pain or degeneration after surgery. The purpose of this study is to determine the impact of the number and position of fixed segments on the SIJs and provide references for surgeons to plan fixation levels and enhance surgical outcomes.MethodsThe intact lumbar‐pelvis finite element (FE) models and 11 fixation FE models with different number and position of fixed segments were developed based on CT images. A 400N follower load and 10° range of motion (ROM) of the spine were applied to the superior endplate of L1 to simulate the flexion, extension, bending and torsion motion after surgery. The peak stress on the SIJs, lumbar intervertebral discs, screws and rods were calculated to evaluate the biomechanical effects of fixation procedures.ResultsWith the lowermost instrumented vertebra (LIV) of L5 or S1, the peak stress on SIJs increased with the number of fixed segments increasing. The flexion motion led to the greater von Mises stress on SIJ compared with other load conditions. Compared with the intact model, peak stress on all fixed intervertebral discs was reduced in the models with less than three fixed segments, and it increased in the models with more than three fixed segments. The stress on the SIJ was extremely high in the models with all segments from L1 to L5 fixed, including L1‐L5, L1‐S1 and L1‐S2 fixation models. The stress on the segment adjacent to the fixed segments was significant higher compared to that in the intact model. The peak stress on rods and screws also increased with the number of fixed segments increasing in the flexion, extension and bending motion, and the bending and flexion motions led to the greater von Mises stress on SIJs.ConclusionShort‐term fixation (≤2 segments) did not increase the stress on the SIJs significantly, while long‐term segment fixation (≥4 segments) led to greater stress on the SIJs especially when all the L1‐L5 segments were fixed. Unfixed lumbar segments compensated the ROM loss of the fixed segments, and the preservation of lumbar spine mobility would reduce the risks of SIJ degeneration.
FHL1: A novel diagnostic marker for papillary thyroid carcinoma
Authors: Zeng Yeting , Zeng Dehua , Qi Xingfeng , Wang Hanxi , Wang Xuzhou , Dai Xiaodong , Qu Lijuan 
Published: August 2024

AbstractAlthough there are clear morphologic criteria for the diagnosis of papillary thyroid carcinoma (PTC), when the morphology is untypical or overlaps, accurate diagnostic indicators are necessary. Since few studies investigated the role of down‐regulated genes in PTC, this article aims to further explore the molecular markers associated with PTC. We conducted bioinformatics analysis of gene microarrays of PTC and normal adjacent tissues. Besides, quantitative real‐time quantitative polymerase chain reaction array and immunohistochemical staining were used to investigate the expression of the major down‐regulated genes. The results indicated that several important down‐regulated genes, including TLE1, BCL2, FHL1, GHR, KIT, and PPARGC1A were involved in the process of PTC. Compared to normal adjacent tissues, the mRNA expression of the major genes was down‐regulated in PTC (p＜0.05). Immunohistochemically, FHL1 shows negative or low expression in PTC tissues (p＜0.05). BCL2 did not show a significant difference between PTC and normal thyroid tissues (p > 0.05). TLE1, KIT, PPARGC1A and GHR showed negative expression in both tumor and normal tissues. These results suggested that FHL1 could serve as a novel tumor marker for precise diagnosis of PTC.
Non‐pharmacological management of wandering in persons with dementia: an integrative review
Authors: Park Sojung , Lee Yaelim 
Published: August 2024

AbstractBackgroundWandering behaviour affects a significant portion of dementia patients, ranging from 15% to 80%, presenting a serious safety concern and adding to caregivers' burden. Recent studies emphasise the effectiveness of non‐pharmacological interventions over pharmacological ones due to their minimal side effects. Consequently, in current literature there has been a surge of interest in exploring non‐pharmacological methods for managing wandering.PurposeThis integrative literature review aims to deepen comprehension of wandering behaviour, presents recent studies on non‐pharmacological approaches, and inspires further research in this field.MethodsElectronic data collection spanned from 2019 to 2024, sourcing 20 relevant articles from PubMed and Scopus databases using search terms such as ‘dementia’, ‘Alzheimer's disease’, ‘wandering’, and ‘management’. A thematic analysis methodology was employed to identify non‐pharmacological treatment themes for managing wandering. This approach involves scrutinising and synthesising themes within the dataset. Qualitative data analysis focused on significant phrases and keywords, grouping them to derive relevant themes.ResultsRecent literature extensively explores non‐pharmacological methods for managing wandering. These include understanding behaviours, identifying and targeting high‐risk groups, facilitating safe wandering, addressing environmental factors, promoting exercise and activity, and offering caregiver support.ConclusionsThis study significantly advances understanding of wandering behaviour and highlights recent research on non‐pharmacological interventions. The findings suggest the potential for providing safe and effective treatment to wandering dementia patients, thereby alleviating stress for both patients and caregivers.
The cofradías’ role within the Fisheries Local Action Groups system: Implications for small‐scale fisheries in Galicia (Spain)
Authors: García‐Lorenzo Iria , Piñeiro‐Antelo María Ángeles , Villasante Sebastián , Pita Pablo 
Published: August 2024

AbstractStructural funds for fisheries have a long history in the European Union, but the use of public funds for the sustainable development of fisheries‐dependent areas is a relatively recent practice. This approach is based on the concept of sustainable fisheries management and focuses on increasing the importance of the involvement of local communities in conservation and management. Fisheries Local Action Groups (FLAGs), created to harmonise social development in a broad sense with the specific, sectoral development of fishing, have become key players in this process in some European countries. In Galicia (NW Spain), FLAGs started to be created in 2008, and soon they were deeply integrated into the small‐scale fisheries (SSF) sector, which was already highly organised. Thus, synergies have been established between cofradías—fisheries organisations with a key role and strong responsibilities in the management of fisheries resources‐ and FLAGs. This article studies the interdependencies between cofradías and FLAGs and how these relationships can influence the development of SSF and their communities. Galician FLAGs and cofradías have created in general positive relationships that contributed to the development of the SSF sector. On the other hand, bureaucratic obligations are concentrated funding in larger cofradías, while the needs of the most vulnerable fishing stakeholders are less covered.