bluuebunny/crossref_metadata_2025_split huggingface dataset:
An intelligent and self-assembled nanoscale metal organic framework (99mTC-DOX loaded Fe3O4@FeIII-tannic acid) for tumor targeted chemo/chemodynamic theranostics
Authors: Swidan Mohamed M. , Wahba Nehal S. , Sakr Tamer M. 
Published: June 2024

Abstract
Background
Recent advances in clinical transformation research have focused on chemodynamic theranostics as an emerging strategy for tackling cancer. Nevertheless, its effectiveness is hampered by the tumor's glutathione antioxidant effect, poor acidic tumor microenvironment (TME) and inadequate endogenous H2O2. Hence, we designed an activatable theranostics (99mTc-DOX loaded AA-Fe3O4@FeIII-TA) that effectively boost the catalytic efficiency of the Fenton-reaction-induced ROS production and augment the chemotherapeutic efficacy combined with diagnostic action.

Results
A cross-linked matrix of tannic acid-ferric salt (FeIII-TA) as a pH-responsive shell onto ascorbic acid-decorated iron-oxide nanoparticles (AA-Fe3O4NPs) was prepared demonstrating a metal–organic- framework (MOF) nanostructure, followed by loading of 99mTc-labelled DOX. The platform (99mTc-DOX loaded AA-Fe3O4@FeIII-TA) displayed suitable physical–chemical properties, including 69.8 nm particle size, 94.8 nm hydrodynamic size, − 21 mV zeta potential, effective FeIII-TA shell crosslinking onto AA-Fe3O4NPs and 94% loading efficiency for 99mTc-DOX. The results of the in-vitro release investigations showed that the platform exhibited a pH-dependent release manner with 98.3% of the 99mTc-DOX being released at pH 5 (simulating the tumor’s pH) and only 10% being released at the physiological pH (pH 7.4). This indicates that there was negligible payload leakage into the systemic circulation during the platform's passive accumulation inside tumor. Due to the acidic TME nature, the MOF shell might be degraded releasing free FeIII, TA and a sustained release of 99mTc-DOX. Besides its chemotherapeutic impact and capacity to raise intracellular H2O2 content, the released 99mTc-DOX might be used as SPECT imaging tracer for concurrent tumor diagnosis. Furthermore, the mild acidity of the tumor may be overcome by the released TA, which might raise the acidification level of cancer cells. The released FeIII, TA and the endogenous GSH could engage in a redox reaction that depletes GSH and reduces FeIII to FeII ions which subsequently catalyze the elevated concentration of H2O2 to reactive •OH via Fenton-like reaction, increasing the effectiveness of chemodynamic therapy. Moreover, the in-vivo evaluation in tumor-bearing mice showed significant radioactivity accumulation in the tumor lesion (16.8%ID/g at 1 h post-injection) with a potential target/non-target ratio of 8.

Conclusions
The 99mTc-DOX loaded AA-Fe3O4@FeIII-TA could be introduced as an effective chemo/chemodynamic theranostics.

Graphical Abstract
ExonSurfer: a web-tool to design primers at exon–exon junctions
Authors: Monfort-Lanzas Pablo , Rusu Elena Cristina , Parrakova Lucia , Karg Cornelia A. , Kernbichler Dorina-Elina , Rieder Dietmar , Lackner Peter , Hackl Hubert , Gostner Johanna M. 
Published: June 2024

Abstract

Background
Reverse transcription quantitative PCR (RT-qPCR) with intercalating dyes is one of the main techniques to assess gene expression levels used in basic and applied research as well as in diagnostics. However, primer design for RT-qPCR can be complex due to the high demands on primer quality. Primers are best placed on exon junctions, should avoid polymorphic regions, be specific to the target transcripts and also prevent genomic amplification accurately, among others. Current software tools manage to meet all the necessary criteria only insufficiently. Here, we present ExonSurfer, a novel, user-friendly web-tool for qPCR primer design.

Results
ExonSurfer combines the different steps of the primer design process, encompassing target selection, specificity and self-complementarity assessment, and the avoidance of issues arising from polymorphisms. Amplification of potentially contaminating genomic DNA is avoided by designing primers on exon-exon junctions, moreover, a genomic alignment is performed to filter the primers accordingly and inform the user of any predicted interaction. In order to test the whole performance of the application, we designed primer pairs for 26 targets and checked both primer efficiency, amplicon melting temperature and length and confirmed the targeted amplicon by Sanger sequencing. Most of the tested primers accurately and selectively amplified the corresponding targets.

Conclusion
ExonSurfer offers a comprehensive end-to-end primer design, guaranteeing transcript-specific amplification. The user interface is intuitive, providing essential specificity and amplicon details. The tool can also be used by command line and the source code is available. Overall, we expect ExonSurfer to facilitate RT-qPCR set-up for researchers in many fields.
Application of artificial neural networks to classify Avena fatua and Avena sterilis based on seed traits: insights from European Avena populations primarily from the Balkan Region
Authors: Oveisi Mostafa , Sikuljak Danijela , Anđelković Ana A. , Bozic Dragana , Trkulja Nenad , Piri Ramin , Poczai Peter , Vrbnicanin Sava 
Published: June 2024

Abstract
Background
Avena fatua and A. sterilis are challenging to distinguish due to their strong similarities. However, Artificial Neural Networks (ANN) can effectively extract patterns and identify these species. We measured seed traits of Avena species from 122 locations across the Balkans and from some populations from southern, western, and central Europe (total over 22 000 seeds). The inputs for the ANN model included seed mass, size, color, hairiness, and placement of the awn attachment on the lemma.

Results
The ANN model achieved high classification accuracy for A. fatua and A. sterilis (R2 > 0.99, RASE < 0.0003) with no misclassification. Incorporating geographic coordinates as inputs also resulted in successful classification (R2 > 0.99, RASE < 0.000001) with no misclassification. This highlights the significant influence of geographic coordinates on the occurrence of Avena species. The models revealed hidden relationships between morphological traits that are not easily detectable through traditional statistical methods. For example, seed color can be partially predicted by other seed traits combined with geographic coordinates. When comparing the two species, A. fatua predominantly had the lemma attachment point in the upper half, while A. sterilis had it in the lower half. A. sterilis exhibited slightly longer seeds and hairs than A. fatua, while seed hairiness and mass were similar in both species. A. fatua populations primarily had brown, light brown, and black colors, while A. sterilis populations had black, brown, and yellow colors.

Conclusions
Distinguishing A. fatua from A. sterilis based solely on individual characteristics is challenging due to their shared traits and considerable variability of traits within each species. However, it is possible to classify these species by combining multiple seed traits. This approach also has significant potential for exploring relationships among different traits that are typically difficult to assess using conventional methods.
Overexpression of PavHIPP16 from Prunus avium enhances cold stress tolerance in transgenic tobacco
Authors: Yu Runrun , Hou Qiandong , Deng Hong , Xiao Ling , Cai Xiaowei , Shang Chunqiong , Qiao Guang 
Published: June 2024

Abstract
Background
The heavy metal-associated isoprenylated plant protein (HIPP) is an important regulatory element in response to abiotic stresses, especially playing a key role in low-temperature response.

Results
This study investigated the potential function of PavHIPP16 up-regulated in sweet cherry under cold stress by heterologous overexpression in tobacco. The results showed that the overexpression (OE) lines’ growth state was better than wild type (WT), and the germination rate, root length, and fresh weight of OE lines were significantly higher than those of WT. In addition, the relative conductivity and malondialdehyde (MDA) content of the OE of tobacco under low-temperature treatment were substantially lower than those of WT. In contrast, peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) activities, hydrogen peroxide (H2O2), proline, soluble protein, and soluble sugar contents were significantly higher than those of WT. Yeast two-hybrid assay (Y2H) and luciferase complementation assay verified the interactions between PavbHLH106 and PavHIPP16, suggesting that these two proteins co-regulated the cold tolerance mechanism in plants. The research results indicated that the transgenic lines could perform better under low-temperature stress by increasing the antioxidant enzyme activity and osmoregulatory substance content of the transgenic plants.

Conclusions
This study provides genetic resources for analyzing the biological functions of PavHIPPs, which is important for elucidating the mechanisms of cold resistance in sweet cherry.
Prevalence of self-reported hearing difficulty on the Revised Hearing Handicap Inventory and associated factors
Authors: Dillard Lauren K. , Matthews Lois J. , Dubno Judy R. 
Published: June 2024

Abstract
Background
Hearing loss is common in aging adults and is an important public health concern. Self-reported measures of hearing difficulty are often used in research and clinical practice, as they capture the functional impacts of hearing loss on individuals. However, little research has evaluated the prevalence or factors associated with self-reported hearing difficulty. Therefore, the purpose of this study was to determine the prevalence of self-reported hearing difficulty, measured by the Revised Hearing Handicap Inventory (RHHI), and associated factors.

Methods
This study was conducted in a community-based cohort study based in Charleston, SC. We determined the prevalence of RHHI self-reported hearing difficulty (score ≥ 6 points) and evaluated associated factors with logistic regression models. Results are presented as odds ratios (OR) with corresponding 95% confidence intervals (95% CI).

Results
There were 1558 participants included in this study (mean age 63.7 [SD 14.4], 56.9% female, 20.0% Minority race). The prevalence of RHHI self-reported hearing difficulty was 48.8%. In a multivariable model, older age (per + 1 year; OR 0.97 [95% CI 0.96, 0.98]), Minority (vs. White) race (OR 0.68 [95% CI 0.49, 0.94]), and speech-in-noise scores that are better than predicted (OR 0.99 [95% CI 0.98, 1.00]) were associated with lower odds of RHHI self-reported hearing difficulty. Furthermore, female (vs. male) sex (OR 1.39 [95% CI 1.03, 1.86]), higher PTA in the worse ear (per + 1 dB; OR 1.10 [95% CI 1.09, 1.12]), more comorbid conditions (vs. 0; 1 condition: OR 1.50 [95% CI 1.07, 2.11]; 2 conditions: OR 1.96 [95% CI 1.32, 2.93]; 3 + conditions: OR 3.00 [95% CI 1.60, 5.62]), noise exposure (OR 1.54 [95% CI 1.16, 2.03]), bothersome tinnitus (OR 2.16 [95% CI 1.59, 2.93]), and more depressive symptoms (OR 1.04 [95% CI 1.01, 1.07]) were associated with higher odds of RHHI self-reported hearing difficulty.

Conclusions
The prevalence of RHHI self-reported hearing difficulty is high, and associated factors included demographics, audiometric hearing and other hearing-related factors, and physical and mental health. The RHHI likely captures functional impacts of hearing loss that are not captured by audiometry alone. Study findings can support the correct interpretation of the RHHI in research and clinical settings.
Pharmacist interventions in Asian healthcare environments for older people: a systematic review and meta-analysis on hospitalization, mortality, and quality of life
Authors: Kim In-Ja , Ryu Gina , Rhie Sandy Jeong , Kim Hwa-Jung 
Published: June 2024

Abstract
Background
Pharmaceutical interventions play a key role in the care of older people experiencing polypharmacy. Despite the rapid increase in the aging population in Asia, there is a lack of evidence regarding the effectiveness of pharmacist interventions on older adult’s healthcare. This systematic review and meta-analysis assessed the effects of pharmacist interventions in Asian health care environments on hospitalization, mortality, and quality of life (QoL) among older people in Asia.

Methods
A comprehensive search was conducted across 5 databases, encompassing studies published from inception through June 2023. Only studies involving pharmacist interventions for people aged 65 years or older, residing in Asian countries, were considered. Studies without evidence of pharmacist involvement or conducted outside of Asia were excluded. Data extraction was performed by two reviewers, one reviewer (I.K.) performed the initial extraction, and another reviewer (G.R.) verified the extracted data. Forest plots were generated using a random effects model to obtain risk ratios or pooled standardized mean differences (SMDs).

Results
A total of 170 articles underwent thorough review, and ultimately, ten studies meeting the inclusion criteria were included in the meta-analyses. These studies encompassed diverse healthcare settings such as outpatient, inpatient, and nursing homes, with sample sizes ranging from 32 to 306 older people. Pharmacist interventions were found to significantly reduce hospitalization rates (n = 5, risk ratio = 0.57, 95% CI = 0.41–0.81) and mortality rates (n = 4, risk ratio = 0.57, 95% CI = 0.37–0.88) among older people. The analysis revealed less significant improvement in QoL in these patients than in those receiving usual care (n = 6, SMD = 0.36, P = 0.057).

Conclusions
These findings highlight the crucial role of pharmacists within healthcare teams in Asian countries. Pharmacist interventions have an impact on reducing hospitalization and mortality rates among the elderly people, underscoring the importance of optimizing patient outcomes in Asia.
Radiomics diagnostic performance for predicting lymph node metastasis in esophageal cancer: a systematic review and meta-analysis
Authors: Ma Dong , Zhou Teli , Chen Jing , Chen Jun 
Published: June 2024

Abstract
Background
Esophageal cancer, a global health concern, impacts predominantly men, particularly in Eastern Asia. Lymph node metastasis (LNM) significantly influences prognosis, and current imaging methods exhibit limitations in accurate detection. The integration of radiomics, an artificial intelligence (AI) driven approach in medical imaging, offers a transformative potential. This meta-analysis evaluates existing evidence on the accuracy of radiomics models for predicting LNM in esophageal cancer.

Methods
We conducted a systematic review following PRISMA 2020 guidelines, searching Embase, PubMed, and Web of Science for English-language studies up to November 16, 2023. Inclusion criteria focused on preoperatively diagnosed esophageal cancer patients with radiomics predicting LNM before treatment. Exclusion criteria were applied, including non-English studies and those lacking sufficient data or separate validation cohorts. Data extraction encompassed study characteristics and radiomics technical details. Quality assessment employed modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Radiomics Quality Score (RQS) tools. Statistical analysis involved random-effects models for pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC). Heterogeneity and publication bias were assessed using Deek’s test and funnel plots. Analysis was performed using Stata version 17.0 and meta-DiSc.

Results
Out of 426 initially identified citations, nine studies met inclusion criteria, encompassing 719 patients. These retrospective studies utilized CT, PET, and MRI imaging modalities, predominantly conducted in China. Two studies employed deep learning-based radiomics. Quality assessment revealed acceptable QUADAS-2 scores. RQS scores ranged from 9 to 14, averaging 12.78. The diagnostic meta-analysis yielded a pooled sensitivity, specificity, and AUC of 0.72, 0.76, and 0.74, respectively, representing fair diagnostic performance. Meta-regression identified the use of combined models as a significant contributor to heterogeneity (p-value = 0.05). Other factors, such as sample size (> 75) and least absolute shrinkage and selection operator (LASSO) usage for feature extraction, showed potential influence but lacked statistical significance (0.05 < p-value < 0.10). Publication bias was not statistically significant.

Conclusion
Radiomics shows potential for predicting LNM in esophageal cancer, with a moderate diagnostic performance. Standardized approaches, ongoing research, and prospective validation studies are crucial for realizing its clinical applicability.
Prediction of cerebral infarction after bypass surgery in adult moyamoya disease: using pulsatility index on TCD
Authors: Ding Jiangbo , Chang Xuying , Ma Peiyu , Yang Guangwu , Zhang Ruoyu , Li Yuanyuan , Lei Ting , Mu Linjie , Zhang Xingkui , Li Zhigao , Tang Jinwei , Tang Zhiwei 
Published: June 2024

Abstract
Background
At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear.

Objective
To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD.

Methods
We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction.

Results
Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients’ ipsilateral MCA-PI were less than 0.614, and another one’s MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009).

Conclusions
A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.
Evaluation of a culture change program to reduce unprofessional behaviours by hospital co-workers in Australian hospitals
Authors: Westbrook Johanna I. , Urwin Rachel , McMullan Ryan , Badgery-Parker Tim , Pavithra Antoinette , Churruca Kate , Cunningham Neil , Loh Erwin , Hibbert Peter , Maddern Guy , Braithwaite Jeffrey , Li Ling 
Published: June 2024

AbstractBackgroundUnprofessional behaviours between healthcare workers are highly prevalent. Evaluations of large-scale culture change programs are rare resulting in limited evidence of intervention effectiveness. We conducted a multi-method evaluation of a professional accountability and culture change program “Ethos” implemented across eight Australian hospitals. The Ethos program incorporates training for staff in speaking-up; an online system for reporting co-worker behaviours; and a tiered accountability pathway, including peer-messengers who deliver feedback to staff for ‘reflection’ or ‘recognition’. Here we report the final evaluation component which aimed to measure changes in the prevalence of unprofessional behaviours before and after Ethos.MethodsA survey of staff (clinical and non-clinical) experiences of 26 unprofessional behaviours across five hospitals at baseline before (2018) and 2.5–3 years after (2021/2022) Ethos implementation. Five of the 26 behaviours were classified as ‘extreme’ (e.g., assault) and 21 as incivility/bullying (e.g., being spoken to rudely). Our analysis assessed changes in four dimensions: work-related bullying; person-related bullying; physical bullying and sexual harassment. Change in experience of incivility/bullying was compared using multivariable ordinal logistic regression. Change in extreme behaviours was assessed using multivariable binary logistic regression. All models were adjusted for respondent characteristics.ResultsIn total, 3975 surveys were completed. Staff reporting frequent incivility/bullying significantly declined from 41.7% (n = 1064; 95% CI 39.7,43.9) at baseline to 35.5% (n = 505; 95% CI 32.8,38.3; χ2(1) = 14.3;P < 0.001) post-Ethos. The odds of experiencing incivility/bullying declined by 24% (adjusted odds ratio [aOR] 0.76; 95% CI 0.66,0.87;P < 0.001) and odds of experiencing extreme behaviours by 32% (aOR 0.68; 95% CI 0.54,0.85;P < 0.001) following Ethos. All four dimensions showed a reduction of 32–41% in prevalence post-Ethos.Non-clinical staff reported the greatest decrease in their experience of unprofessional behaviour (aOR 0.41; 95% CI 0.29, 0.61). Staff attitudes and reported skills to speak-up were significantly more positive at follow-up. Awareness of the program was high (82.1%; 95% CI 80.0, 84.0%); 33% of respondents had sent or received an Ethos message.ConclusionThe Ethos program was associated with significant reductions in the prevalence of reported unprofessional behaviours and improved capacity of hospital staff to speak-up. These results add to evidence that staff will actively engage with a system that supports informal feedback to co-workers about their behaviours and is facilitated by trained peer messengers.