bluuebunny/crossref_metadata_2025 huggingface dataset:
The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study
Authors: Stastna Nela , Hrabovska Lenka , Homolka Pavel , Homola Lukas , Svoboda Michal , Brat Kristian , Fila Libor
Published: May 2024

Background

Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated.

Methods

We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients.

Results

We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters.

Conclusion

Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.
Preoperative and follow-up variations of psoas major muscle are related to S1 screw loosening in patients with degenerative lumbar spinal stenosis
Authors: Zhou Siyu , Xu Fei , Sun Zhuoran , Jiang Shuai , Li Zhuofu , Han Gengyu , Li Weishi
Published: May 2024

Background

It was reported the paraspinal muscle played an important role in spinal stability. The preoperative paraspinal muscle was related to S1 screw loosening. But the relationship between preoperative and postoperative change of psoas major muscle (PS) and S1 pedicle screw loosening in degenerative lumbar spinal stenosis (DLSS) patients has not been reported. This study investigated the effects of preoperative and follow-up variations in the psoas major muscle (PS) on the first sacral vertebra (S1) screw loosening in patients with DLSS.

Methods

212 patients with DLSS who underwent lumbar surgery were included. The patients were divided into the S1 screw loosening group and the S1 screw non-loosening group. Muscle parameters were measured preoperatively and at last follow-up magnetic resonance imaging. A logistic regression analysis was performed to investigate the risk factors for S1 screw loosening.

Results

The S1 screw loosening rate was 36.32% (77/212). The relative total cross-sectional areas and relative functional cross-sectional areas (rfCSAs) of the PS at L2–S1 were significantly higher after surgery. The increased rfCSA values of the PS at L3–S1 in the S1 screw non-loosening group were significantly higher than those in the S1 screw loosening group. The regression analysis showed male, lower CT value of L1 and longer segment fusion were independent risk factors for S1 screw loosening, and postoperative hypertrophy of the PS was a protective factor for S1 screw loosening.

Conclusions

Compared to the preoperative muscle, the PS size increased and fatty infiltration decreased after surgery from L2–3 to L5–S1 in patients with DLSS after short-segment lumbar fusion surgery. Postoperative hypertrophy of the PS might be considered as a protective factor for S1 screw loosening. MRI morphometric parameters and postoperative selected exercise of PS for DLSS patients after posterior lumbar fusion surgery might contribute to improvement of surgical outcome.
Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring F1 hybrids
Authors: Boman Jesper , Qvarnström Anna , Mugal Carina F.
Published: May 2024

Background

Regulation of transcription by DNA methylation in 5’-CpG-3’ context is a widespread mechanism allowing differential expression of genetically identical cells to persist throughout development. Consequently, differences in DNA methylation can reinforce variation in gene expression among cells, tissues, populations, and species. Despite a surge in studies on DNA methylation, we know little about the importance of DNA methylation in population differentiation and speciation. Here we investigate the regulatory and evolutionary impact of DNA methylation in five tissues of two Ficedula flycatcher species and their naturally occurring F1 hybrids.

Results

We show that the density of CpG in the promoters of genes determines the strength of the association between DNA methylation and gene expression. The impact of DNA methylation on gene expression varies among tissues with the brain showing unique patterns. Differentially expressed genes between parental species are predicted by genetic and methylation differentiation in CpG-rich promoters. However, both these factors fail to predict hybrid misexpression suggesting that promoter mismethylation is not a main determinant of hybrid misexpression in Ficedula flycatchers. Using allele-specific methylation estimates in hybrids, we also determine the genome-wide contribution of cis- and trans effects in DNA methylation differentiation. These distinct mechanisms are roughly balanced in all tissues except the brain, where trans differences predominate.

Conclusions

Overall, this study provides insight on the regulatory and evolutionary impact of DNA methylation in songbirds.
Information technology-supported integrated health service for older adults in long-term care settings
Authors: Choi Jung-Yeon , Kim Hongsoo , Chun Seungyeon , Jung Young-il , Yoo Sooyoung , Oh In-Hwan , Kim Gi-Soo , Ko Jin Young , Lim Jae-Young , Lee Minho , Lee Jongseon , Kim Kwang-il
Published: May 2024

Background

To examine the effectiveness and safety of a data sharing and comprehensive management platform for institutionalized older patients.

Methods

We applied information technology-supported integrated health service platform to patients who live at long-term care hospitals (LTCHs) and nursing homes (NHs) with cluster randomized controlled study. We enrolled 555 patients aged 65 or older (461 from 7 LTCHs, 94 from 5 NHs). For the intervention group, a tablet-based platform comprising comprehensive geriatric assessment, disease management, potentially inappropriate medication (PIM) management, rehabilitation program, and screening for adverse events and warning alarms were provided for physicians or nurses. The control group was managed with usual care. Co-primary outcomes were (1) control rate of hypertension and diabetes, (2) medication adjustment (PIM prescription rate, proportion of polypharmacy), and (3) combination of potential quality-of-care problems (composite quality indicator) from the interRAI assessment system which assessed after 3-month of intervention.

Results

We screened 1119 patients and included 555 patients (control; 289, intervention; 266) for analysis. Patients allocated to the intervention group had better cognitive function and took less medications and PIMs at baseline. The diabetes control rate (OR = 2.61, 95% CI 1.37–4.99, p = 0.0035), discontinuation of PIM (OR = 4.65, 95% CI 2.41–8.97, p < 0.0001), reduction of medication in patients with polypharmacy (OR = 1.98, 95% CI 1.24–3.16, p = 0.0042), and number of PIMs use (ꞵ =  − 0.27, p < 0.0001) improved significantly in the intervention group. There was no significant difference in hypertension control rate (OR = 0.54, 95% CI 0.20–1.43, p = 0.2129), proportion of polypharmacy (OR = 1.40, 95% CI 0.75–2.60, p = 0.2863), and improvement of composite quality indicators (ꞵ = 0.03, p = 0.2094). For secondary outcomes, cognitive and motor function, quality of life, and unplanned hospitalization were not different significantly between groups.

Conclusions

The information technology-supported integrated health service effectively reduced PIM use and controlled diabetes among older patients in LTCH or NH without functional decline or increase of healthcare utilization.

Trial registration

Clinical Research Information Service, KCT0004360. Registered on 21 October 2019.
CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis
Authors: Zhang Xiao-Yu , Li Shan-Shan , Gu Yu-Rong , Xiao Le-Xin , Ma Xin-Yi , Chen Xin-Ru , Wang Jia-Liang , Liao Chun-Hong , Lin Bing-Liang , Huang Yue-Hua , Lian Yi-Fan
Published: May 2024

Background

The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development.

Methods

Functional analyses were conducted to assess circPIAS1’s impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1’s effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms.

Results

CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib.

Conclusion

This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.
miR-92b-3p protects retinal tissues against DNA damage and apoptosis by targeting BTG2 in experimental myopia
Authors: Liu Jinpeng , Bao Bo , Li Tuling , Yang Zhaohui , Du Yongle , Zhang Ruixue , Xin Jizhao , Hao Jiawen , Wang Guimin , Bi Hongsheng , Guo Dadong
Published: May 2024

Background

Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2.

Methods

Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting.

Results

Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia.

Conclusion

In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.

Graphical Abstract
Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs
Authors: Tran Nhi T. , Hale Nadia , Maung Anawar Aung Win , Wiersma Manon , Walker David W. , Polglase Graeme , Castillo-Melendez Margie , Wong Flora Y.
Published: May 2024

Background

Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses.

Methods

At 119–120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3–4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit.

Results

LPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte “end feet” vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS.

Conclusion

LPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.
Maternal employment characteristics as a structural social determinant of breastfeeding after return to work in the European Region: a scoping review
Authors: Brugaillères Pauline , Deguen Séverine , Lioret Sandrine , Haidar Sahar , Delamaire Corinne , Counil Emilie , Vandentorren Stéphanie
Published: May 2024

Background

The European Region has the lowest rate of exclusive breastfeeding at 6 months worldwide. Improving work-related breastfeeding issues is important given that women may have difficulties combining work and breastfeeding, especially those in precarious working situations, which adds to their adversity. This scoping review overviews research on the maternal employment characteristics that support breastfeeding continuation after return to work in the European Region.

Methods

Studies published from 2013 to 2023 were collected from Scopus, PubMed, and PsycInfo. Quantitative and qualitative studies published in English or French that explored the association between maternal employment characteristics and any breastfeeding status, duration, or experience were included. Participants included were mothers of healthy children who continued breastfeeding after resuming work. The main determinants were work-related factors that can lead to socially differentiated working conditions, including type of employment (e.g., occupation, employed/self-employed status, type of contract, working time, occupational prestige), working conditions (e.g., work schedule, decision latitude, latitude to organize worktime), and work environment (e.g., occupational exposure, family-friendly workplace policy, social support). The geographic area encompassed countries included in the World Health Organization European Region.

Results

Of the 693 single studies retrieved and screened, 13 were included in the review. Eight studies focused on combining work and breastfeeding, while the others had a broader spectrum by investigating breastfeeding determinants. The represented countries were Spain (n = 4), France (n = 4), UK (n = 2), Ireland (n = 2), and the Netherlands (n = 1). Results highlighted the heterogeneity of measures, time frames, and fields of inquiry, thus revealing a lack of conceptual framework regarding the links between work, breastfeeding, and social health inequalities. Nonetheless, being self-employed, working in a non-manual profession with time flexibility, having lactation rooms at work, being supported by co-workers, and having a breastfeeding workplace policy were salient factors that supported breastfeeding in working mothers.

Conclusions

Supporting working mothers who choose to breastfeed is important given the myriad of adverse factors faced by mothers and their children. These results advocate for targeted actions at the workplace such as time flexibility, breastfeeding facilities, and the promotion of breastfeeding-friendly policies.
Exploring the content and delivery of feedback facilitation co-interventions: a systematic review
Authors: Sykes Michael , Rosenberg-Yunger Zahava R. S. , Quigley Matthew , Gupta Lavanya , Thomas Owen , Robinson Lisa , Caulfield Karen , Ivers Noah , Alderson Sarah
Published: May 2024

Background

Policymakers and researchers recommend supporting the capabilities of feedback recipients to increase the quality of care. There are different ways to support capabilities. We aimed to describe the content and delivery of feedback facilitation interventions delivered alongside audit and feedback within randomised controlled trials.

Methods

We included papers describing feedback facilitation identified by the latest Cochrane review of audit and feedback. The piloted extraction proforma was based upon a framework to describe intervention content, with additional prompts relating to the identification of influences, selection of improvement actions and consideration of priorities and implications. We describe the content and delivery graphically, statistically and narratively.

Results

We reviewed 146 papers describing 104 feedback facilitation interventions. Across included studies, feedback facilitation contained 26 different implementation strategies. There was a median of three implementation strategies per intervention and evidence that the number of strategies per intervention is increasing. Theory was used in 35 trials, although the precise role of theory was poorly described. Ten studies provided a logic model and six of these described their mechanisms of action. Both the exploration of influences and the selection of improvement actions were described in 46 of the feedback facilitation interventions; we describe who undertook this tailoring work. Exploring dose, there was large variation in duration (15–1800 min), frequency (1 to 42 times) and number of recipients per site (1 to 135). There were important gaps in reporting, but some evidence that reporting is improving over time.

Conclusions

Heterogeneity in the design of feedback facilitation needs to be considered when assessing the intervention’s effectiveness. We describe explicit feedback facilitation choices for future intervention developers based upon choices made to date. We found the Expert Recommendations for Implementing Change to be valuable when describing intervention components, with the potential for some minor clarifications in terms and for greater specificity by intervention providers. Reporting demonstrated extensive gaps which hinder both replication and learning. Feedback facilitation providers are recommended to close reporting gaps that hinder replication. Future work should seek to address the ‘opportunity’ for improvement activity, defined as factors that lie outside the individual that make care or improvement behaviour possible.

Review registration

The study protocol was published at: https://www.protocols.io/private/4DA5DE33B68E11ED9EF70A58A9FEAC02.
Biallelic variants in LARS1 induce steatosis in developing zebrafish liver via enhanced autophagy
Authors: Inoue Masanori , Sebastian Wulan Apridita , Sonoda Shota , Miyahara Hiroaki , Shimizu Nobuyuki , Shiraishi Hiroshi , Maeda Miwako , Yanagi Kumiko , Kaname Tadashi , Hanada Reiko , Hanada Toshikatsu , Ihara Kenji
Published: May 2024

Background

Biallelic pathogenic variants of LARS1 cause infantile liver failure syndrome type 1 (ILFS1), which is characterized by acute hepatic failure with steatosis in infants. LARS functions as a protein associated with mTORC1 and plays a crucial role in amino acid-triggered mTORC1 activation and regulation of autophagy. A previous study demonstrated that larsb-knockout zebrafish exhibit conditions resembling ILFS. However, a comprehensive analysis of larsb-knockout zebrafish has not yet been performed because of early mortality.

Methods

We generated a long-term viable zebrafish model carrying a LARS1 variant identified in an ILFS1 patient (larsb-I451F zebrafish) and analyzed the pathogenesis of the affected liver of ILFS1.

Results

Hepatic dysfunction is most prominent in ILFS1 patients during infancy; correspondingly, the larsb-I451F zebrafish manifested hepatic anomalies during developmental stages. The larsb-I451F zebrafish demonstrates augmented lipid accumulation within the liver during autophagy activation. Inhibition of DGAT1, which converts fatty acids to triacylglycerols, improved lipid droplets in the liver of larsb-I451F zebrafish. Notably, treatment with an autophagy inhibitor ameliorated hepatic lipid accumulation in this model.

Conclusions

Our findings suggested that enhanced autophagy caused by biallelic LARS1 variants contributes to ILFS1-associated hepatic dysfunction. Furthermore, the larsb-I451F zebrafish model, which has a prolonged survival rate compared with the larsb-knockout model, highlights its potential utility as a tool for investigating the pathophysiology of ILFS1-associated liver dysfunction.
Macintosh-style videolaryngoscope use for tracheal intubation in elective surgical patients revisited: a sub-analysis of the 2022 Cochrane review data
Authors: McNarry Alistair F. , Ward Patrick , Silas Ubong , Saunders Rhodri , Saunders Sita J.
Published: May 2024

The Cochrane systematic review and meta-analysis published in 2022 that compared videolaryngoscopy (VL) with direct laryngoscopy (DL) for facilitating tracheal intubation in adults found that all three types of VL device (Macintosh-style, hyper-angulated and channeled) reduced the risk of failed intubation and increased the likelihood of first-pass success. We report the findings of a subgroup re-analysis of the 2022 Cochrane meta-analysis data focusing on the Macintosh-style VL group. This was undertaken to establish whether sufficient evidence exists to guide airway managers in making purchasing decisions for their local institutions based upon individual device-specific performance. This re-analysis confirmed the superiority of Macintosh-style VL over Macintosh DL in elective surgical patients, with similar efficacy demonstrated between the Macintosh-style VL devices examined. Thus, when selecting which VL device(s) to purchase for their hospital, airway managers decisions are likely to remain focused upon issues such as financial costs, portability, cleaning schedules and previous device experience.
ePRINT: exonuclease assisted mapping of protein-RNA interactions
Authors: Hawkins Sophie , Mondaini Alexandre , Namboori Seema C. , Nguyen Grady G. , Yeo Gene W. , Javed Asif , Bhinge Akshay
Published: May 2024

RNA-binding proteins (RBPs) regulate key aspects of RNA processing including alternative splicing, mRNA degradation and localization by physically binding RNA molecules. Current methods to map these interactions, such as CLIP, rely on purifying single proteins at a time. Our new method, ePRINT, maps RBP-RNA interaction networks on a global scale without purifying individual RBPs. ePRINT uses exoribonuclease XRN1 to precisely map the 5′ end of the RBP binding site and uncovers direct and indirect targets of an RBP of interest. Importantly, ePRINT can also uncover RBPs that are differentially activated between cell fate transitions, including neural progenitor differentiation into neurons.
Hematological and plasma profiles and ticks and tick-borne pathogens in wild Formosan black bears (Ursus thibetanus formosanus)
Authors: Tsai Yi-Lun , Wechtaisong Wittawat , Lee Ting-Rong , Chang Chun-Hao , Yu Pin-Huan , Hwang Mei-Hsiu
Published: May 2024

Background

The endangered Formosan black bear (Ursus thibetanus formosanus) is the largest native carnivorous mammal in Taiwan. Diseases, poor management, illegal hunting, and habitat destruction are serious threats to the survival of bear populations. However, studies on the impact of diseases on bear populations are limited. Therefore, this study aimed to establish a database of the hematological and plasma profiles of free-ranging Formosan black bears and investigate the occurrence of ectoparasites, blood parasites, and vector-borne pathogens.

Methods

Formosan black bears were captured in Yushan National Park (YNP) and Daxueshan Forest Recreation Area (DSY) in Taiwan. Blood samples were collected from each bear for hematological analysis and plasma biochemistry using a hematology analyzer. Parasites and pathogens were detected using a thin blood smear with Wright–Giemsa staining and polymerase chain reaction (PCR) assay. Additionally, macroscopic ectoparasites were collected from bears to detect blood parasites and other pathogens. Moreover, the relationships between the bear variables (sex, age, and occurrence of parasites or pathogens), ectoparasites, and infectious agents were also analyzed.

Results

In all, 21 wild bears (14 in YNP and 7 in DSY) were captured and released during the satellite tracking studies. Hematological analysis and plasma biochemistry indicated significant differences in white blood cells (WBC), segments, creatine kinase (CK), and lactate dehydrogenase (LDH) levels between foot snare and culvert-captured bears. Additionally, there were significant differences in total plasma protein (TPP), creatinine, Ca2+, Mg2+, and K+ levels between male and female bears. Moreover, pathogen-infected bears had significantly higher erythrocyte sedimentation rate (ESR; 30 min and 1 h) and globulin levels than uninfected bears. In total, 240 ticks were collected from 13 bears, among which eight adult tick species were identified, including Haemaphysalis flava, Haemaphysalis hystricis, Amblyomma testudinarium, Ixodes ovatus, Dermacentor taiwanensis, Haemaphysalis longicornis, Ixodes acutitarsus, Amblyomma javanense, and nymphs belonging to Haemaphysalis spp. PCR revealed that 13 (61.90%) and 8 (38.10%) bears harbored Hepatozoon ursi and Babesia DNA, respectively. Among the ticks examined, 157 (65.41%) and 128 (53.33%) samples were positive for H. ursi and Babesia, respectively.

Conclusions

To the best of our knowledge, this is the first study to establish a database of the hematological and plasma profiles of wild Formosan black bears and investigate ectoparasite infestation and Hepatozoon and Babesia spp. infection. In conclusion, these findings may serve as a reference for monitoring the health and population of locally endangered bears.

Graphical Abstract
Consensus holistic virtual screening for drug discovery: a novel machine learning model approach
Authors: Moshawih Said , Bu Zhen Hui , Goh Hui Poh , Kifli Nurolaini , Lee Lam Hong , Goh Khang Wen , Ming Long Chiau
Published: May 2024

In drug discovery, virtual screening is crucial for identifying potential hit compounds. This study aims to present a novel pipeline that employs machine learning models that amalgamates various conventional screening methods. A diverse array of protein targets was selected, and their corresponding datasets were subjected to active/decoy distribution analysis prior to scoring using four distinct methods: QSAR, Pharmacophore, docking, and 2D shape similarity, which were ultimately integrated into a single consensus score. The fine-tuned machine learning models were ranked using the novel formula “w_new”, consensus scores were calculated, and an enrichment study was performed for each target. Distinctively, consensus scoring outperformed other methods in specific protein targets such as PPARG and DPP4, achieving AUC values of 0.90 and 0.84, respectively. Remarkably, this approach consistently prioritized compounds with higher experimental PIC50 values compared to all other screening methodologies. Moreover, the models demonstrated a range of moderate to high performance in terms of R2 values during external validation. In conclusion, this novel workflow consistently delivered superior results, emphasizing the significance of a holistic approach in drug discovery, where both quantitative metrics and active enrichment play pivotal roles in identifying the best virtual screening methodology.

Scientific contribution

We presented a novel consensus scoring workflow in virtual screening, merging diverse methods for enhanced compound selection. We also introduced ‘w_new’, a groundbreaking metric that intricately refines machine learning model rankings by weighing various model-specific parameters, revolutionizing their efficacy in drug discovery in addition to other domains.

Graphical Abstract
Relational aggression in romantic relationship: empirical evidence among young female adults in Malaysia
Authors: Kamaluddin Mohammad Rahim , Munusamy Shalini , Sheau Tsuey Chong , Abdullah & Mohd Nor Hilwa
Published: May 2024

Background

Aggressive behaviour in romantic relationship is a social problem of great concern. Studies related to the influence of psychosocial factors on relational aggression are still limited. Furthermore, these factors have not been widely studied in the local context, resulting in the issue of relational aggression among young female adults still not being addressed. This study aims to explore whether psychosocial factors such as big five personality traits, adult attachment style and loneliness could predict relational aggression in romantic relationships among young female adults in Malaysia. In addition, this study aims to identify the moderating effect of social support in the relationship between psychosocial factors and relational aggression in romantic relationship.

Methods

A quantitative research approach was used with 424 young female adults in Malaysia aged between 18 and 30 years old (mean age = 24.18) were recruited through multistage sampling design by completing a questionnaire consisting of the Big Five Inventory (BFI), Experiences in Close Relationships Scale II (ECRS-II), Revised UCLA Loneliness Scale, Measure of Relational Aggression and Victimization (MRAV) and Multidimensional Scale of Perceived Social Support (MSPSS).

Results

Multiple regression analysis predicted significant relationship between agreeableness personality, loneliness, avoidant attachment style and anxious attachment style with relational aggression in romantic relationships. Hierarchical regression analysis found a significant effect of social support as a moderator between loneliness with relational aggression in romantic relationships.

Conclusions

Thus, the results show that young female adults with low level of agreeableness, high level of loneliness, avoidant attachment style and anxious attachment style are at a higher risk of engaging in relational aggression in romantic relationships. The implication of this study can help in understanding the psychosocial factors that form the basis of relational aggression in romantic relationships. Hence, the gap in knowledge warrants further research.
Associations between perceived occupational stressors and symptoms severity of depression, anxiety and stress among academic faculty: First cross-sectional study from Qatar
Authors: Hammoudi Halat Dalal , Abdel-Rahman Manar E. , Al-Jayyousi Ghadir Fakhri , Malki Ahmed
Published: May 2024

Background

Mental health concerns among university faculty are on the rise, with reports of anxiety, depression, and occupational stress, impacting the higher education community. In Qatar, an assessment of faculty mental health has not been previously realized. The objectives of the current study were twofold: Firstly, to evaluate the extent of perceived occupational stress, depression, anxiety, and stress, and secondly, to assess the association among these mental health parameters.

Methods

A cross-sectional study was conducted among faculty using an online, self-administered, anonymous, voluntary survey. All faculty were included by sending the survey to their institutional emails. In addition to faculty demographics and general health status, the survey measured perceived stress due to academic job roles using the Faculty Stress Index (FSI) with its five distinct domains, and assessed faculty mental health using the Depression, Anxiety, and Stress Scale-21 items (DASS-21). Modified Poisson regression with robust variance was used to assess how FSI influences levels of depression, anxiety, and stress.

Results

A total of 112 faculty responded to the survey. The highest faculty self-perceptions of mental health conditions were for anxiety (63% at least moderate), followed by depression (30% at least moderate), and least for stress (26% at least moderate). The overall mean FSI score was 48.8 ± 29.4; time constraint and rewards and recognition domains scored highest (18.5 ± 11.4 and 13.3 ± 9.3 respectively) while the departmental influence domain scored least (4.8 ± 4.4). Increased risk of at least moderate levels of self-perceived depression and stress were significantly associated with higher FSI score (p˂0.001). Increased risk of at least moderate levels of depression were less likely among faculty aged 50 years and above (p = 0.034), while increased risk of at least moderate levels of anxiety were more likely among faculty from humanities colleges (p = 0.027).

Conclusions

This is the first investigation of university faculty mental health in Qatar, indicating multifactorial perceived occupational stress, associated with higher perceived severity of mental health conditions. These baseline results establish links between specific occupational stressors for faculty and their mental well-being. As such, assessment of mental health conditions, controlling occupational stress, and developing tailored mental health interventions for faculty, are strategic to implement and foster well-being of academics. Further research into mental health of faculty and designing effective interventions that consider their specific stressors and associated factors are warranted.
Reliability and validity of simple Chinese version of grit scale for elementary school students
Authors: Jie Wang , Xinyi Wang , Tao Xin
Published: May 2024

Background

The Grit scale (GS-12) is a widely used rating scale that assess passion and perseverance. The present study aimed to evaluate the reliability and validity of simple Chinese Version of Grit Scale (GS-SC) among Chinese adolescents.

Methods

Seven hundred one primary school students were recruited as Sample 1. Item analysis and exploratory factor analysis (EFA) were conducted on Sample 1 to preliminarily examine the structure of the scale. Sample 2 consisted of 5,384 primary school students. Confirmatory factor analysis (CFA) and verification of reliability and validity were conducted on Sample 2 to establish a formal scale and further verify the psychometric properties by applying item response theory (IRT).

Results

EFA and CFA revealed a clear two-factor structure. The results demonstrated that the Simplified Chinese Version of Grit Scale had adequate internal consistency and re-test reliability. GS-CS also showed good criterion-validity with personality, self-control, effort regulation and academic achievement. Furthermore, all the items show a acceptable fit to the GRM and have good discrimination (ranging from 2.13 to 3.45) and moderate difficulty(ranging from-1.58 to 0.95).

Conclusions

The reliability and validity of the GS-SC are good, indicating that the scale can be used as an effective tool for measuring the grit of primary school students in China.
Sustainable development and formative evaluation of mathematics open educational resources created by pre-service teachers: an action research study
Authors: Lo Chung Kwan , Ng Fletcher , Cheung Ka Luen
Published: May 2024

In the post-pandemic world, UNESCO advocates the development of open educational resources (OER) to remedy the financial pressures of students and their families. We thus conducted a dual-cycle action research study aiming to develop a sustainable model with minimal cost for creating OER for secondary school mathematics teachers and students. Our theoretical foundations drew upon existing sustainable models of OER development and experiential learning theory to enhance the efficacy of OER. Formative evaluation techniques were employed in both action research cycles, where pre-service teachers developed the OER and in-service teachers provided suggestions for improvement. In the second cycle, we tested the use of our OER with 35 Grade 11 students to examine both student achievement and retention. The test results showed a significant learning gain (pre-test: Mdn = 2.00; post-test: Mdn = 10.00), which was retained over 2 weeks (delayed post-test: Mdn = 11.00). However, the students’ performance on more advanced questions was not satisfactory. Based on an overall reflection on the study, we proposed a sustainable model of OER development, which leveraged the manpower of pre-service and in-service teachers and incorporated formative evaluation techniques. Furthermore, we provided recommendations for enhancing the future development of OER in mathematics education.
Interaction-focused music therapy with cancer-affected children and their significant others: a randomized controlled feasibility study with subsequent intervention (INMUT)
Authors: Boyde Constance , Berger Bettina , Längler Alfred , Neugebauer Lutz , Jacobsen Stine Lindahl , Swanick Rachel , Gaebel Christine , Schneider Dominik , Bernbeck Benedikt , Paulussen Michael , Ostermann Thomas , Hunger-Schoppe Christina
Published: May 2024

Background

Paediatric oncology/haematology patients and their families are confronted with a life-threatening situation for which music therapy can be a cross-linguistic field of action. The creative act of making music together offers the possibility to strengthen competences and make conflicts tangible. Besides its complementing of evidence-based biomedical care, there is little research on the feasibility and efficacy of interactive music therapy including the diagnosed child and their significant others.

Methods

We conducted an assessor blind, prospective, multicentric feasibility randomized controlled trial (RCT) with subsequent intervention. Including overall 52 child-significant other dyads, INMUT investigates interaction-focused music therapy with cancer-affected children and their significant others (INMUT-KB; n = 21) compared to music therapy only with the child (MUT-K; n = 21) and a wait-list group (WLG; n = 10). The measurement points include the screening for a cancer diagnosis, psychometric baseline (pre-T1), initial assessment (T1/T2), music therapy sessions (T3–T9), final assessment (T10), final psychometric evaluation (post-T10), and 3-month follow-up (cat-T11). Feasibility and acceptability of the (1) research methodology, (2) intervention and (3) estimation of effect sizes will be assessed using qualitative and quantitative data. The proposed primary outcome includes the parent–child interaction (APCI), and the proposed secondary outcomes refer to subjective goal achievement (GAS), quality of life (KINDL), system-related functional level (EXIS), psychosocial stress (BAS), psychosomatic complaints (SCL-9k), and resources (WIRF). We plan to investigate the efficacy of INMUT-KB and MUT-K post-intervention (post-T10) within the RCT design and at 3-month follow-up (cat-T11).

Discussion

This study will provide insights into the feasibility of INMUT and the final sample needed for a confirmatory RCT. We will reflect on successfully implemented study procedures and, if necessary, provide recommendations for changes considering the design, procedures, measures, and statistical analyses. The discussion will conclude with an evaluation whether a confirmatory RCT is worth the investment of future resources, including the calculated number of child-significant other dyads needed based on the efficacy trends derived from this feasibility study.

Trial registration

ClinicalTrials.gov: NCT05534282; date of registration: June 23, 2022.
Between meeting quotas and following the duty-bound heart: navigating the formidable dilemma of refugee protection in the EU
Authors: Efthymiou Dimitrios
Published: May 2024

The provision of refuge to those fleeing persecution and danger is a complex matter that cannot be reduced to simply meeting admission quotas. While numerical targets for refugee admissions may seem like a straightforward way to ensure states are doing their fair share, an overemphasis on numbers risks obscuring the deeper moral issues at play. A truly robust approach to refugee protection requires that states act from the right kinds of reasons - a genuine commitment to the duty to provide safe haven to all refugees, regardless of their country of origin or the political expediency of admitting them. The worry is that if a state’s willingness to accept refugees fluctuates based on domestic political preferences and perceptions of national interest, rather than an unwavering recognition of the moral claims of the forcibly displaced, then the protection provided to refugees becomes contingent and precarious. A disposition to selectively protect only certain refugees undermines the very concept of refuge. However, in our non-ideal world, a commitment to the principle of robust refugee protection can run up against the hard reality of state non-compliance. If the only way to get some states to fulfil their duties is to allow them leeway in choosing which refugees to admit, we face a serious moral dilemma. Relaxing the demands of robustness may enable larger raw numbers of people to access refuge in the near term. However, it also risks eroding the norm of impartial consideration and creating a two-tier system of refugee protection. Ultimately, I argue, the dilemma between refugee numbers and robustness has no fully satisfying solution - it is an unavoidable product of our current circumstances of injustice and non-compliance. The best we can do is seek arrangements that ease this tension over time. This requires taking a nuanced, context-sensitive approach attuned to real-world constraints and trade-offs while still keeping sight of the moral lodestar of genuinely unconditional refuge for all who need it.
Music therapy for Alzheimer’s disease management: a narrative review
Authors: Nikkhah Bahrami Sahar , Momtazmanesh Sara , Rezaei Nima
Published: May 2024

Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, is escalating globally. Characterized by cognitive decline, emotional instability, and neuropsychiatric symptoms, AD presents a growing challenge for effective management. Current pharmaceutical treatments, primarily acetylcholinesterase inhibitors and memantine, offer symptomatic relief but fail to halt disease progression or significantly address psychiatric manifestations. Consequently, non-pharmacological interventions, particularly music therapy, have garnered attention as potential adjunctive treatments. Musical memory is regarded as completely distinct from other memory processes, and patients with AD retain some musical recall despite the significant cognitive decline. In addition, music therapy is well-tolerated by the vast majority of patients and easy to administer. Herein, the mechanisms of music as a memory enhancer, how musical memory is preserved in AD, active and passive music therapy methods and their effects on each function, and factors affecting the efficacy of music therapy, such as music selection and genre, are discussed. Additional research is required to determine the optimal duration of music therapy sessions for patients to experience long-term benefits. In addition, as patients in severe stages cannot participate fully in music therapy sessions due to their disability, additional research finding a solution to this issue would be helpful.
Determinant factors of banking profitability: an application of quantile regression for panel data
Authors: Bortoluzzo Adriana Bruscato , Ciganda Rodrigo Ricardo , Bortoluzzo Mauricio Mesquita
Published: May 2024

This study examines the determinants of bank profitability using a quantile regression approach, offering insights into factors affecting banks across different percentiles of profitability. Utilizing a comprehensive database from Orbis covering 1200 top-market institutions across 101 countries, the research uniquely employs dynamic panel quantile regression while addressing sample survival bias. Our findings highlight that bank size and capital adequacy negatively impact profitability, whereas market value exerts a positive influence on higher profitability banks. Credit risk affects profitability differently across levels of profitability, and inflation rate shows significance only for higher profitability banks. The study contributes to the existing literature by offering valuable insights into the factors determining bank profitability and how they behave at different percentiles in the sample, suggesting the importance of bank efficiency and competition in promoting economic growth.