bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxyurea pharmacokinetics and precision dosing in low-resource settings
Authors: Smart Luke R. , Charles Mwesige , McElhinney Kathryn E. , Dong Min , Power-Hays Alexandra , Howard Thad , Vinks Alexander A. , Ambrose Emmanuela E. , Ware Russell E.
Published: June 2023

Introduction: Hydroxyurea is effective disease-modifying treatment for sickle cell anemia (SCA). Escalation to maximum tolerated dose (MTD) achieves superior benefits without additional toxicities, but requires dose adjustments with serial monitoring. Pharmacokinetic (PK)-guided dosing can predict a personalized optimal dose, which approximates MTD and requires fewer clinical visits, laboratory assessments, and dose adjustments. However, PK-guided dosing requires complex analytical techniques unavailable in low-resource settings. Simplified hydroxyurea PK analysis could optimize dosing and increase access to treatment.

Methods: Concentrated stock solutions of reagents for chemical detection of serum hydroxyurea using HPLC were prepared and stored at −80C. On the day of analysis, hydroxyurea was serially diluted in human serum, then spiked with N-methylurea as an internal standard and analyzed using two commercial HPLC machines: 1) standard benchtop Agilent with 449 nm detector and 5 micron C18 column; and 2) portable PolyLC with 415 nm detector and 3.5 micron C18 column. After validation in the United States, the portable HPLC and chemicals were transported to Tanzania.

Results: A calibration curve using hydroxyurea 2-fold dilutions ranging from 0 to 1000 µM was plotted against the hydroxyurea:N-methylurea ratio. In the United States, both HPLC systems yielded calibration curves with R2 > 0.99. Hydroxyurea prepared at known concentrations confirmed accuracy and precision within 10%–20% of the actual values. Both HPLC systems measured hydroxyurea with <10% variance from the prepared concentrations, and paired analysis of samples on both machines documented <15% variance. Serial measurements of 300 and 100 μM concentrations using the PolyLC system were precise with 2.5% coefficient of variance. After transport to Tanzania with setup and training, the modified PolyLC HPLC system produced similar calibration curves with R2 > 0.99.

Conclusion: Increasing access to hydroxyurea for people with SCA requires an approach that eases financial and logistical barriers while optimizing safety and benefits, especially in low-resource settings. We successfully modified a portable HPLC instrument to quantify hydroxyurea, validated its precision and accuracy, and confirmed capacity building and knowledge transfer to Tanzania. HPLC measurement of serum hydroxyurea is now feasible in low-resource settings using available laboratory infrastructure. PK-guided dosing of hydroxyurea will be tested prospectively to achieve optimal treatment responses.
Q1291H-CFTR molecular dynamics simulations and ex vivo theratyping in nasal epithelial models and clinical response to elexacaftor/tezacaftor/ivacaftor in a Q1291H/F508del patient
Authors: Allan Katelin M. , Astore Miro A. , Kardia Egi , Wong Sharon L. , Fawcett Laura K. , Bell Jessica L. , Visser Simone , Chen Po-Chia , Griffith Renate , Jaffe Adam , Sivam Sheila , Vittorio Orazio , Kuyucak Serdar , Waters Shafagh A.
Published: June 2023

Background: Cystic fibrosis (CF) is caused by a wide spectrum of mutations in the CF transmembrane conductance regulator (CFTR) gene, with some leading to non-classical clinical presentations. We present an integrated in vivo, in silico and in vitro investigation of an individual with CF carrying the rare Q1291H-CFTR allele and the common F508del allele. At age 56 years, the participant had obstructive lung disease and bronchiectasis, qualifying for Elexacaftor/Tezacaftor/Ivacaftor (ETI) CFTR modulator treatment due to their F508del allele. Q1291H CFTR incurs a splicing defect, producing both a normally spliced but mutant mRNA isoform and a misspliced isoform with a premature termination codon, causing nonsense mediated decay. The effectiveness of ETI in restoring Q1291H-CFTR is largely unknown.

Methods: We collected clinical endpoint measurements, including forced expiratory volume in 1 s percent predicted (FEV1pp) and body mass index (BMI), and examined medical history. In silico simulations of the Q1291H-CFTR were compared to Q1291R, G551D, and wild-type (WT)-CFTR. We quantified relative Q1291H CFTR mRNA isoform abundance in patient-derived nasal epithelial cells. Differentiated pseudostratified airway epithelial cell models at air liquid interface were created and ETI treatment impact on CFTR was assessed by electrophysiology assays and Western blot.

Results: The participant ceased ETI treatment after 3 months due to adverse events and no improvement in FEV1pp or BMI. In silico simulations of Q1291H-CFTR identified impairment of ATP binding similar to known gating mutants Q1291R and G551D-CFTR. Q1291H and F508del mRNA transcripts composed 32.91% and 67.09% of total mRNA respectively, indicating 50.94% of Q1291H mRNA was misspliced and degraded. Mature Q1291H-CFTR protein expression was reduced (3.18% ± 0.60% of WT/WT) and remained unchanged with ETI. Baseline CFTR activity was minimal (3.45 ± 0.25 μA/cm2) and not enhanced with ETI (5.73 ± 0.48 μA/cm2), aligning with the individual’s clinical evaluation as a non-responder to ETI.

Conclusion: The combination of in silico simulations and in vitro theratyping in patient-derived cell models can effectively assess CFTR modulator efficacy for individuals with non-classical CF manifestations or rare CFTR mutations, guiding personalized treatment strategies and optimizing clinical outcomes.
The time squares sequences: a new task for assessing visuospatial working memory
Authors: Mirino Pierandrea , Mercuri Sara , Pecchinenda Anna , Boccia Maddalena , Di Piero Andrea , Soldani Marta , Guariglia Cecilia
Published: June 2023

Introduction

Several studies have shown that the working memory is sensitive to temporal variations. We used a new visuospatial working memory task, the “Time Squares Sequences,” to investigate whether implicit variations in stimuli presentation time affect task performance.

Methods

A total of 50 healthy participants saw two sequences (S1 and S2) of seven white squares presented in a matrix of gray squares and assessed whether S2 matched S1. There were four conditions depending on the spatial position and the presentation time (i.e., timing) of the white squares in S1 and S2: two with the same (S1 fixed/S2 fixed and S1 variable/S2 variable) and two with different (S1 fixed/S2 variable and S1 variable/S2 fixed) presentation times.

Results

Findings showed impaired performance when S1 had a fixed presentation time and S2 had a variable presentation time.

Conclusion

These findings are attributed to increased cognitive load due to S2 timing difference, pointing to a monitoring process, sensitive to temporal variations.
Improved multi-objective artificial bee colony algorithm-based path planning for mobile robots
Authors: Cui Qiuyu , Liu Pengfei , Du Hualong , Wang He , Ma Xin
Published: June 2023

Mobile robots are widely used in various fields, including cosmic exploration, logistics delivery, and emergency rescue and so on. Path planning of mobile robots is essential for completing their tasks. Therefore, Path planning algorithms capable of finding their best path are needed. To address this challenge, we thus develop improved multi-objective artificial bee colony algorithm (IMOABC), a Bio-inspired algorithm-based approach for path planning. The IMOABC algorithm is based on multi-objective artificial bee colony algorithm (MOABC) with four strategies, including external archive pruning strategy, non-dominated ranking strategy, crowding distance strategy, and search strategy. IMOABC is tested on six standard test functions. Results show that IMOABC algorithm outperforms the other algorithms in solving complex multi-objective optimization problems. We then apply the IMOABC algorithm to path planning in the simulation experiment of mobile robots. IMOABC algorithm consistently outperforms existing algorithms (the MOABC algorithm and the ABC algorithm). IMOABC algorithm should be broadly useful for path planning of mobile robots.
Mitoepigenetics and gliomas: epigenetic alterations to mitochondrial DNA and nuclear DNA alter mtDNA expression and contribute to glioma pathogenicity
Authors: Grady Clare I. , Walsh Lisa M. , Heiss John D.
Published: June 2023

Epigenetic mechanisms allow cells to fine-tune gene expression in response to environmental stimuli. For decades, it has been known that mitochondria have genetic material. Still, only recently have studies shown that epigenetic factors regulate mitochondrial DNA (mtDNA) gene expression. Mitochondria regulate cellular proliferation, apoptosis, and energy metabolism, all critical areas of dysfunction in gliomas. Methylation of mtDNA, alterations in mtDNA packaging via mitochondrial transcription factor A (TFAM), and regulation of mtDNA transcription via the micro-RNAs (mir 23-b) and long noncoding RNAs [RNA mitochondrial RNA processing (RMRP)] have all been identified as contributing to glioma pathogenicity. Developing new interventions interfering with these pathways may improve glioma therapy.
Cognitive rehabilitation in paediatric acquired brain injury—A 2-year follow-up of a randomised controlled trial
Authors: Sargénius Hanna L. , Andersson Stein , Haugen Ingvild , Hypher Ruth , Brandt Anne Elisabeth , Finnanger Torun G. , Rø Torstein B. , Risnes Kari , Stubberud Jan
Published: June 2023

Background

Goal management training (GMT), a metacognitive rehabilitation method that has been demonstrated to improve executive function (EF) in adults with acquired brain injury (ABI), could potentially be effective for children in the chronic phase of ABI. In a previously published randomised controlled trial (RCT), the efficacy of a paediatric adaptation of GMT (pGMT) compared to a psychoeducative control intervention (paediatric Brain Health Workshop, pBHW) was investigated. Comparable improvements in EF in both groups were found at 6-month follow-up. However, a specific effect of pGMT could not be conclusively proven. The present study reports 2-year follow-up data (T4; T1: baseline, T2: post-intervention, T3: 6-month follow-up, and T4: 2-year follow-up) from this original RCT.

Methods

A total of 38 children and adolescents and also their parents completed questionnaires tapping into daily life EF. Explorative analyses were conducted comparing the 2-year follow-up data (T4) with the baseline (T1) and 6-month follow-up data (T3) for T4-participants in the two intervention groups (pGMT; n = 21, pBHW; n = 17), and we also assessed T4-participants vs. non-responders (n = 38) in the RCT. Primary outcome measures were the Behavioural Regulation Index (BRI) and the Metacognition Index (MI) derived from the Behaviour Rating Inventory of Executive Function (BRIEF) parent report.

Results

No difference between intervention groups was found (BRI, F = 2.25, p = 0.143, MI, F = 1.6, p = 0.213), and no time*group interaction (BRI, F = 0.07, p = 0.976, MI, F = 0.137, p = 0.937) could be seen at the 2-year follow-up. Nevertheless, both pGMT and the pBHW groups improved daily EF as measured by parental reports over time from the baseline to T4 (p = 0.034). T4 participants and non-responders shared similar baseline characteristics.

Conclusion

Our results extend the findings from the 6-month follow-up previously published. Both pGMT and pBHW groups sustained their improvements in daily life EFs from the baseline, but additional effectiveness of pGMT relative to pBHW was not found.
Mind wandering state detection during video-based learning via EEG
Authors: Tang Shaohua , Liang Yutong , Li Zheng
Published: June 2023

The aim of this study is to explore the potential of technology for detecting mind wandering, particularly during video-based distance learning, with the ultimate benefit of improving learning outcomes. To overcome the challenges of previous mind wandering research in ecological validity, sample balance, and dataset size, this study utilized practical electroencephalography (EEG) recording hardware and designed a paradigm consisting of viewing short-duration video lectures under a focused learning condition and a future planning condition. Participants estimated statistics of their attentional state at the end of each video, and we combined this rating scale feedback with self-caught key press responses during video watching to obtain binary labels for classifier training. EEG was recorded using an 8-channel system, and spatial covariance features processed by Riemannian geometry were employed. The results demonstrate that a radial basis function kernel support vector machine classifier, using Riemannian-processed covariance features from delta, theta, alpha, and beta bands, can detect mind wandering with a mean area under the receiver operating characteristic curve (AUC) of 0.876 for within-participant classification and AUC of 0.703 for cross-lecture classification. Furthermore, our results suggest that a short duration of training data is sufficient to train a classifier for online decoding, as cross-lecture classification remained at an average AUC of 0.689 when using 70% of the training set (about 9 min). The findings highlight the potential for practical EEG hardware in detecting mind wandering with high accuracy, which has potential application to improving learning outcomes during video-based distance learning.
Novel approach to investigate the association between type 2 diabetes risk and dietary fats in a dietary pattern context: a scoping review
Authors: Brayner Barbara , Kaur Gunveen , Keske Michelle A. , Marchese Laura E. , Livingstone Katherine M.
Published: June 2023

The effect of dietary fat on type 2 diabetes (T2D) risk is unclear. A posteriori dietary pattern methods have been increasingly used to investigate how dietary fats impact T2D risk. However, the diverse nutrients, foods and dietary patterns reported in these studies requires examination to better understand the role of dietary fats. This scoping review aimed to systematically search and synthesize the literature regarding the association between dietary patterns characterized by dietary fats and T2D risk using reduced rank regression. Medline and Embase were searched for cross-sectional, cohort or case-control studies published in English. Of the included studies (n = 8), five high-fat dietary patterns, mostly high in SFA, were associated with higher T2D risk or fasting glucose, insulin and Homeostasis Model Assessment (HOMA) levels. These were mostly low-fiber (n = 5) and high energy-density (n = 3) dietary patterns characterized by low fruit and vegetables intake, reduced fat dairy products and higher processed meats and butter intake. Findings from this review suggest that a posteriori dietary patterns high in SFA that increase T2D risk are often accompanied by lower fruits, vegetables and other fiber-rich foods intake. Therefore, healthy dietary fats consumption for T2D prevention should be encouraged as part of a healthful dietary pattern.
Feasibility of the Omaha system for the care of children with dilated cardiomyopathy
Authors: Zhang Qin , Zhang Ai , Wang Yanqin , Lv Tiewei , Sun Ping , Zhao Xiaoxia , Li Rui , Zheng Xianlan
Published: June 2023

Aim

To explore the feasibility of Omaha system theory in the care of children with dilated cardiomyopathy (DCM), which may provide a practical basis for the continuous nursing of DCM children.

Methods

A total of 1,392 records describing symptoms, signs, and nursing interventions were extracted from the medical records of 76 children suffered from DCM. Content analysis method was used to find out existent nursing problems, make precise nursing plans, and take corresponding nursing measurements according to the medical records of DCM children. Cross-mapping method was utilized to compare the conceptual consistency of the medical records and Omaha system (problem classification and intervention subsystems).

Results

Of the total 1,392 records, 1,094 (78.59%) were complete consistency, while 245 (17.60%) were partial consistency, and 53 (3.81%) were inconsistency with the Omaha system concepts. The concept matching degree of medical records and Omaha system was approximately 96.19%.

Conclusions

The Omaha system may be an effective nursing language for Chinese DCM children, which may be useful to guide nurses in the care of DCM. Further well-design studies need to fully evaluate the feasibility and effectiveness of the Omaha system in nursing children with DCM.
Gut microbiome-mediated mechanisms in aging-related diseases: are probiotics ready for prime time?
Authors: Ren Jing , Li Huimin , Zeng Guixing , Pang Boxian , Wang Qiuhong , Wei Junping
Published: June 2023

Chronic low-grade inflammation affects health and is associated with aging and age-related diseases. Dysregulation of the gut flora is an important trigger for chronic low-grade inflammation. Changes in the composition of the gut flora and exposure to related metabolites have an effect on the inflammatory system of the host. This results in the development of crosstalk between the gut barrier and immune system, contributing to chronic low-grade inflammation and impairment of health. Probiotics can increase the diversity of gut microbiota, protect the gut barrier, and regulate gut immunity, thereby reducing inflammation. Therefore, the use of probiotics is a promising strategy for the beneficial immunomodulation and protection of the gut barrier through gut microbiota. These processes might positively influence inflammatory diseases, which are common in the elderly.
Efficacy and safety of pharmacotherapy for recurrent high-grade glioma: a systematic review and network meta-analysis
Authors: Xu Yanan , Guan Haijing , Yu Kefu , Ji Nan , Zhao Zhigang
Published: June 2023

Objective: To compare the efficacy and safety of treatments for patients with recurrent high-grade gliomas.

Methods: Electronic databases including Pubmed, Embase, Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials (RCT) related to high-grade gliomas. The inclusion of qualified literature and extraction of data were conducted by two independent reviewers. The primary clinical outcome measures of network meta-analysis were overall survival (OS) while progression-free survival (PFS), objective response rate (ORR) and adverse event of grade 3 or higher were secondary measures.

Results: 22 eligible trials were included in the systematic review, involving 3423 patients and 30 treatment regimens. Network meta-analysis included 11 treatments of 10 trials for OS and PFS, 10 treatments of 8 trials for ORR, and 8 treatments of 7 trials for adverse event grade 3 or higher. Regorafenib showed significant benefits in terms of OS in paired comparison with several treatments such as bevacizumab (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.21–0.73), bevacizumab plus carboplatin (HR, 0.33; 95%CI, 0.16–0.68), bevacizumab plus dasatinib (HR, 0.44; 95%CI, 0.21–0.93), bevacizumab plus irinotecan (HR, 0.4; 95%CI, 0.21–0.74), bevacizumab plus lomustine (90 mg/m2) (HR, 0.53; 95%CI, 0.33–0.84), bevacizumab plus lomustine (110 mg/m2) (HR, 0.21; 95%CI, 0.06–0.7), bevacizumab plus vorinostat (HR, 0.42; 95%CI, 0.18–0.99), lomustine (HR, 0.5; 95%CI, 0.33–0.76), and nivolumab (HR, 0.38; 95%CI, 0.19–0.73). For PFS, only the hazard ratio between bevacizumab plus vorinostat and bevacizumab plus lomustine (90 mg/m2) was significant (HR,0.51; 95%CI, 0.27–0.95). Lomustine and nivolumab conferred worse ORR. Safety analysis showed fotemustine as the best and bevacizumab plus temozolomide as the worst.

Conclusion: The results suggested that regorafenib and bevacizumab plus lomustine (90 mg/m2) provide improvements in terms of survival but may have poor ORR in patients with recurrent high-grade glioma.
The suppression of the probe laser pumping effect in SERF atomic magnetometer
Authors: Cao Qian , Zhai Yueyang , Huang Binyue , Li Renjie , Li Jiajie
Published: June 2023

Introduction: A spin exchange relaxation free atomic magnetometer, as an ultra-highly sensitive magnetic field sensor, is limited by the performance of the probe laser system. The probe laser pumping effect (PLPE) hinders the increase in the performance of probe laser system.

Methods: This study investigated the PLPE and proposed a method for suppressing the same. Through changes to the angle of a quarter wave plate and the addition of a triangular modulated magnetic field to the alkali atoms, the suppression point was determined.

Results and discussion: Further, related parameters were measured for different degree of polarizations of the probe laser, which confirmed that the influence of PLPE on the magnetic field was the least at the suppressed point.
Performance analysis of the coherent FMCW photonic radar system under the influence of solar noise
Authors: Kumari Annapurna , Kumar Amitesh , Reddy Gurijala Sai Tejesh
Published: June 2023

The real-time high-resolution target detection in radar applications has increased the demand for photonic radar systems due to their higher bandwidth and faster processing capabilities over conventional microwave radar. Additionally, photonic-based radar technology can revolutionize the limited performance of conventional microwave radar caused by various atmospheric attenuations. This article presents a frequency-modulated continuous-wave photonic radar system using coherent detection. The performance of the proposed system is theoretically investigated under the effect of various real-time atmospheric weather attenuations and the influence of solar background noise, which is further verified on the simulation platform. This study is conducted under different atmospheric weather conditions, such as clear, haze, and fog, to highlight the practical limitation of free-space links in the presence of solar background noise. The detected signal at different target ranges with and without solar noise is measured and then compared in terms of signal-to-noise ratio. Furthermore, the impact of solar noise on the system performance when the Sun is under different sky conditions and zenithal angles is also analyzed. The results presented here provide insights into designing photonic radar systems for practical applications like autonomous vehicle radar systems, self-traffic control, and navigation.
Photoplethysmography upon cold stress—impact of measurement site and acquisition mode
Authors: Fleischhauer Vincent , Bruhn Jan , Rasche Stefan , Zaunseder Sebastian
Published: June 2023

Photoplethysmography (PPG) allows various statements about the physiological state. It supports multiple recording setups, i.e., application to various body sites and different acquisition modes, rendering the technique a versatile tool for various situations. Owing to anatomical, physiological and metrological factors, PPG signals differ with the actual setup. Research on such differences can deepen the understanding of prevailing physiological mechanisms and path the way towards improved or novel methods for PPG analysis. The presented work systematically investigates the impact of the cold pressor test (CPT), i.e., a painful stimulus, on the morphology of PPG signals considering different recording setups. Our investigation compares contact PPG recorded at the finger, contact PPG recorded at the earlobe and imaging PPG (iPPG), i.e., non-contact PPG, recorded at the face. The study bases on own experimental data from 39 healthy volunteers. We derived for each recording setup four common morphological PPG features from three intervals around CPT. For the same intervals, we derived blood pressure and heart rate as reference. To assess differences between the intervals, we used repeated measures ANOVA together with paired t-tests for each feature and we calculated Hedges’ g to quantify effect sizes. Our analyses show a distinct impact of CPT. As expected, blood pressure shows a highly significant and persistent increase. Independently of the recording setup, all PPG features show significant changes upon CPT as well. However, there are marked differences between recording setups. Effect sizes generally differ with the finger PPG showing the strongest response. Moreover, one feature (pulse width at half amplitude) shows an inverse behavior in finger PPG and head PPG (earlobe PPG and iPPG). In addition, iPPG features behave partially different from contact PPG features as they tend to return to baseline values while contact PPG features remain altered. Our findings underline the importance of recording setup and physiological as well as metrological differences that relate to the setups. The actual setup must be considered in order to properly interpret features and use PPG. The existence of differences between recording setups and a deepened knowledge on such differences might open up novel diagnostic methods in the future.
PRDM16 regulates arterial development and vascular integrity
Authors: Thompson Michael , Sakabe Masahide , Verba Mark , Hao Jiukuan , Meadows Stryder M. , Lu Q. Richard , Xin Mei
Published: June 2023

Proper vascular formation is regulated by multiple signaling pathways. The vascular endothelial growth factor (VEGF) signaling promotes endothelial proliferation. Notch and its downstream targets act to lead endothelial cells toward an arterial fate through regulation of arterial gene expression. However, the mechanisms of how endothelial cells (ECs) in the artery maintain their arterial characteristics remain unclear. Here, we show that PRDM16 (positive regulatory domain-containing protein 16), a zinc finger transcription factor, is expressed in arterial ECs, but not venous ECs in developing embryos and neonatal retinas. Endothelial-specific deletion of Prdm16 induced ectopic venous marker expression in the arterial ECs and reduced vascular smooth muscle cell (vSMC) recruitment around arteries. Whole-genome transcriptome analysis using isolated brain ECs show that the expression of Angpt2 (encoding ANGIOPOIETIN2, which inhibits vSMC recruitment) is upregulated in the Prdm16 knockout ECs. Conversely, forced expression of PRDM16 in venous ECs is sufficient to induce arterial gene expression and repress the ANGPT2 level. Together, these results reveal an arterial cell-autonomous function for PRDM16 in suppressing venous characteristics in arterial ECs.
Small fish, big discoveries: zebrafish shed light on microbial biomarkers for neuro-immune-cardiovascular health
Authors: Sree Kumar Hemaa , Wisner Alexander S. , Refsnider Jeanine M. , Martyniuk Christopher J. , Zubcevic Jasenka
Published: June 2023

Zebrafish (Danio rerio) have emerged as a powerful model to study the gut microbiome in the context of human conditions, including hypertension, cardiovascular disease, neurological disorders, and immune dysfunction. Here, we highlight zebrafish as a tool to bridge the gap in knowledge in linking the gut microbiome and physiological homeostasis of cardiovascular, neural, and immune systems, both independently and as an integrated axis. Drawing on zebrafish studies to date, we discuss challenges in microbiota transplant techniques and gnotobiotic husbandry practices. We present advantages and current limitations in zebrafish microbiome research and discuss the use of zebrafish in identification of microbial enterotypes in health and disease. We also highlight the versatility of zebrafish studies to further explore the function of human conditions relevant to gut dysbiosis and reveal novel therapeutic targets.
Improving field establishment and yield in seed propagated Miscanthus through manipulating plug size, sowing date and seedling age
Authors: Ashman Chris , Wilson Rebecca , Mos Michal , Clifton-Brown John , Robson Paul
Published: June 2023

Biomass crops provide significant potential to substitute for fossil fuels and mitigate against climate change. It is widely acknowledged that significant scale up of biomass crops is required to help reach net zero targets. Miscanthus is a leading biomass crop embodying many characteristics that make it a highly sustainable source of biomass but planted area remains low. Miscanthus is commonly propagated via rhizome, but efficient alternatives may increase uptake and help diversify the cultivated crop. Using seed-propagate plug plants of Miscanthus has several potential benefits such as improving propagation rates and scale up of plantations. Plugs also provide an opportunity to vary the time and conditions under protected growth, to achieve optimal plantlets before planting. We varied combinations of glasshouse growth period and field planting dates under UK temperate conditions, which demonstrated the special importance of planting date on yield, stem number and establishment rates of Miscanthus. We also propagated Miscanthus in four different commercial plug designs that contained different volumes of substrate, the resulting seedlings were planted at three different dates into field trials. In the glasshouse, plug design had significant effects on above and belowground biomass accumulation and at a later time point belowground growth was restricted in some plug designs. After subsequent growth in the field, plug design and planting date had a significant effect on yield. The effects of plug design on yield were no longer significant after a second growth season but planting date continued to have a significant effect. After the second growth year, it was found that planting date had a significant effect on surviving plants, with the mid-season planting producing higher survival rates over all plug types.Establishment was positively correlated with DM biomass produced in the first growth season. Sowing date had a significant effect on establishment but the impacts of plug design were more nuanced and were significant at later planting dates. We discuss the potential to use the flexibility afforded by seed propagation of plug plants to deliver significant impacts in achieving high yield and establishment of biomass crops during the critical first two years of growth.
Re-sequencing and morphological data revealed the genetics of stone shell and kernel traits in apricot
Authors: Zhang Qiuping , Zhang Yuping , Liu Weisheng , Liu Ning , Ma Xiaoxue , Lü Chunjing , Xu Ming , Liu Shuo , Zhang Yujun
Published: June 2023

Kernel-using apricot (Prunus armeniaca L.) is an economically important fruit tree species in arid areas owing to its hardiness and cold and drought tolerance. However, little is known about its genetic background and trait inheritances. In the present study, we first evaluated the population structure of 339 apricot accessions and the genetic diversity of kernel-using apricots using whole genome re-sequencing. Second, the phenotypic data of 222 accessions were investigated for two consecutive seasons (2019 and 2020) for 19 traits, including kernel and stone shell traits and the pistil abortion rate of flowers. Heritability and correlation coefficient of traits were also estimated. The stone shell length (94.46%) showed the highest heritability, followed by the length/width ratio (92.01%) and length/thickness ratio (92.00%) of the stone shell, whereas breaking force of the nut (17.08%) exhibited a very low heritability. A genome-wide association study (GWAS) using general linear model and generalized linear mixed model revealed 122 quantitative trait loci (QTLs). The QTLs of the kernel and stone shell traits were unevenly assigned on the eight chromosomes. Out of the 1,614 candidate genes identified in the 13 consistently reliable QTLs found using the two GWAS methods and/or in the two seasons, 1,021 were annotated. The sweet kernel trait was assigned to chromosome 5 of the genome, similar to the almond, and a new locus was also mapped at 17.34–17.51 Mb on chromosome 3, including 20 candidate genes. The loci and genes identified here will be of significant use in molecular breeding efforts, and the candidate genes could play essential roles in exploring the mechanisms of genetic regulation.
Are “bad” jobs bad for democracy? Precarious work and electoral participation in Europe
Authors: Azzollini Leo , Macmillan Ross
Published: June 2023

Introduction

While socioeconomic inequality in voting has been central for research on electoral participation, recent years have seen radical changes in labor relations. The key issue is increasing prevalence of precarious work, involving dimensions as non-indefinite tenure and limited control over work activities. While occupations traditionally were the locus of political socialization, there is scarce research connecting occupational uncertainty to electoral participation. To fill this void, we develop a framework that connects the multiple dimensions of precarious work to electoral participation.

Methods

We test these ideas using data from 32 countries from the European Social Survey (2008–2018).

Results and discussion

Results indicate that work precarity is both strongly connected to traditional indicators of SES and has large, independent effects on probability of voting. We corroborate these results with heterogeneity analyses across countries. Findings show how precarious work heightens socio-economic stratification in electoral participation, undermining the universality of the right to vote and the health of democracies.
Trauma-focused treatment for traumatic stress symptoms in unaccompanied refugee minors: a multiple baseline case series
Authors: Van Es Carlijn Maria , Velu Merel E. , Sleijpen Marieke , van der Aa Niels , Boelen Paul A. , Mooren Trudy
Published: June 2023

Introduction

Unaccompanied refugee minors (URMs) are at increased risk of developing mental health problems, such as symptoms of posttraumatic stress disorder (PTSD) and depression. In addition, URMs face several barriers to mental health care. Few studies have evaluated trauma-focused interventions for URMs that target these issues. The current study evaluated a multimodal trauma-focused treatment approach for URMs. It aimed to provide an initial indication of the effectiveness of this treatment approach and to provide a qualitative evaluation assessing treatment satisfaction of the participating URMs.

Methods

A mixed-methods study was conducted among ten URMs, combining quantitative data with qualitative data through triangulation. Quantitative data were collected using a non-concurrent multiple baseline design in which repeated, weekly assessments were carried out during a randomized baseline period, during treatment, and during a 4-week follow-up period. Questionnaires assessing PTSD (Children’s Revised Impact of Event Scale) and symptoms of depression (The Patient Health Questionnaire-9, modified for adolescents) were used. In addition, treatment satisfaction was measured post-treatment using a semi-structured interview.

Results

During the qualitative evaluation, all but one URM noted they found the trauma-focused treatment approach useful and felt the treatment had positively impacted their wellbeing. However, the results of the quantitative evaluation did not show clinically reliable symptom reductions at posttest or follow-up. Implications for clinical practice and research are discussed.

Discussion

The current study presents our search in developing a treatment approach for URMs. It adds to the current knowledge about methodological considerations in evaluating treatments for URMs, the potential effects of trauma-focused treatments on URMs, and the implementation of treatments for URMs.

Clinical trial registration: The study was registered in the Netherlands Trial Register (NL8519), 10 April 2020.
Dropout in youth and adult education: a multilevel analysis of students and schools in Chile
Authors: Contreras-Villalobos Tabata , López Verónica , Baleriola Enrique , González Luis
Published: June 2023

Introduction

School dropout is an increasing worldwide phenomenon, marked by inequality and educational exclusion. In Chile, many students who have dropped out of regular schools attempt to reenter youth and adult education (YAE). However, some of them drop out again from YAE.

Objective

The aim of this study was to identify and jointly analyze school and individual factors that influence dropout in YAE.

Methods

This secondary multilevel analysis of official datasets from Chile’s Ministry of Education focused on students enrolled in YAE (N = 10,130).

Results

According to the findings, YAE dropout can be explained by the individual risk factors of age (19–24 years), low academic achievement, and school-level factors such as number of teachers (raw and student-to-teacher ratio), economic resources, and school management quality.

Discussion

We discuss the need to develop school-level protective factors that build connections, foster student engagement, and ultimately, promote students’ permanence and progress in YAE.
Free-Association Session Scale: factor structure and preliminary validity test
Authors: Mariani Rachele , Di Monte Cinzia , Caricati Luca , Bastianini Tiziana , Ferruta Anna , Christopher Christian , Speranza Anna Maria , Guerrini degli Innocenti Benedetta , Musetti Alessandro
Published: June 2023

One of the main concepts of the psychoanalytic method postulated by Freud in 1912 is the fundamental rule, which involves asking the patient to say whatever comes to mind as the analyst follows the patient's speech with fluctuating attention. Despite different theoretical models, this concept has remained an invariant element that characterizes the psychoanalytic method. For this reason, the purpose of the current study is to present a new instrument that measures this process based on the clinician's assessment. The Free-Association Session Scale (FASS) has been designed according to the psychoanalytic framework. Study 1 presented the preliminary validation of the FASS factor structure. Experienced Italian psychoanalysts (N = 281; 196 women) completed the FASS and sociodemographic questionnaire. The following two factors were identified using exploratory factor analysis: (1) Perturbing, and (2) Associativity. Study 2 cross-validated the two factors using an independent sample (N = 259; 187 women) of experienced psychoanalysts and confirmatory factor analysis (CFA). The FASS has been tested for concurrent validity using the Session Evaluation Questionnaire (SEQ) and Linguistic measures of the Referential process. The two-factor model achieved a close-fit test, and the FASS items were found to measure the corresponding factors with good reliability. The Perturbing factor is negatively associated with three SEQ factors (Depth, Smoothness, and Positivity) and negatively correlated with symbolization (IWRAD and IWRAD_IWRRL), confirming a more complex and unexpected session. The Associativity factor is positively associated with all four SEQ factors (Depth, Smoothness, Positivity, and Arousal). In conclusion, the FASS is a promising new questionnaire for assessing psychoanalytic session quality processes with satisfactory validity and reliability.
Prescription drug dependence with and without concurrent illicit drug use: a multicenter cross-sectional survey among an addiction treatment seeking population
Authors: Nawaz Asma , Nielsen Suzanne , Mehmood Tahir , Abdullah Abdullah , Ahmed Ali , Ullah Waseem , Khan Ahmad
Published: June 2023

Background

Dependence on prescription drugs and illicit drugs imposes a global health and social burden. Despite accumulating evidence of prescription drugs and illicit drugs dependence, none of the systematized studies has explored the magnitude of this problem in Pakistan. The aim is to investigate the extent and associated factors of prescription drug dependence (PDD), as opposed to concomitant prescription drug dependence and illicit drug use (PIDU), within a sample of individuals seeking addiction treatment.

Methods

The cross sectional study was conducted on the sample recruited from three drug treatment centers in Pakistan. Face-to-face interviews were conducted with participants who met ICD-10 criteria for prescription drug dependence. Several aspects like substance use histories, negative health outcomes, patient attitude, pharmacy and physician practices also collected to predict the determinants of (PDD). Binomial logistic regression models examined the factors associated with PDD and PIDU.

Results

Of the 537 treatment seeking individuals interviewed at baseline, close to one third (178, 33.3%) met criteria for dependence on prescription drugs. The majority of the participants were male (93.3%), average age of 31 years, having urban residence (67.4%). Among participants who met criteria for dependence on prescription drugs (71.9%), reported benzodiazepines as the most frequently used drug, followed by narcotic analgesics (56.8%), cannabis/marijuana (45.5%), and heroin (41.5%). The patients reported alprazolam, buprenorphine, nalbuphine, and pentazocin use as alternatives to illicit drugs. PDD was significantly negatively associated with injectable route (OR = 0.281, 95% CI, 0.079–0.993) and psychotic symptoms (OR = 0.315, 95% CI, 0.100, 0.986). This implies that PDD is less likely to be associated with an injectable route and psychotic symptoms in contrast to PIDU. Pain, depression and sleep disorder were primary reasons for PDD. PDD was associated with the attitude that prescription drugs are safer than illicit drugs (OR = 4.057, 95%CI, 1.254–13.122) and PDD was associated with being on professional terms (i.e., having an established relationship) with pharmaceutical drugs retailers for acquisition of prescription drugs.

Discussion and conclusion

The study found benzodiazepine and opioid dependence in sub sample of addiction treatment seekers. The results have implications for drug policy and intervention strategies for preventing and treating drug use disorders.
Sleep disorders in chronic pain and its neurochemical mechanisms: a narrative review
Authors: Duo Lan , Yu Xintong , Hu Ruihan , Duan Xiping , Zhou Jia , Wang Ke
Published: June 2023

Chronic pain (CP) is a prevalent problem, and more than half of patients with CP have sleep disorders. CP comorbidity with sleep disorders imposes immense suffering and seriously affects the patient’s quality of life, which is a challenging issue encountered by clinicians. Although the reciprocal interactions between pain and sleep have been studied to some degree, there is still a lack of awareness and comprehensive description of CP comorbidity with sleep disorders. In this narrative review article, we summarize the current knowledge about the present estimates of the prevalence of comorbid sleep disorders in CP patients, sleep detection methods, sleep characterization in CP, and the effect of sleep disorders on CP and current therapies. We also summarize current knowledge of the neurochemical mechanisms of CP comorbidity with sleep disorders. In conclusion, insufficient attention has been paid to the role of sleep disorders in CP patients, and CP patients should be screened for sleep disorders in the clinic. Special attention should be given to a possible risk of drug–drug interaction when using two types of drugs targeting pain and sleep simultaneously. The current insight into the neurobiological mechanisms underlying CP comorbidity with sleep disorders is still rather limited.
Behind the scenes of the healthcare COVID-19 pandemic crisis: potential affecting factors of healthcare work sustainability in Romania during 2020–2022
Authors: Savu Cristina , Armaș Iuliana , Burcea Marin , Dobre Daniela
Published: June 2023

Aim

The COVID-19 pandemic represented a great disturbance for medical systems around the world, putting medical personnel on the front lines of the fight against the SARS-Cov2 virus. This fight was particularly impactful in countries with medical systems already facing various challenges, including Romania; where the pandemic unfolded in five waves that severely affected the psychological and physical well-being of medical professionals in terms of overload and continuous exposure to health threats. Against this background, our research aims to identify the mediating role of potential affecting factors of healthcare work sustainability during the change-related uncertainty conditions generated by the COVID 19 crisis. Dynamics and relations of nine carefully selected constructs were tracked along all five pandemic waves in Romania, which span from March 2020 to April 2022. The tested variables and constructs are perception of healthcare workers of their own state of health, their workplace safety, the work–family conflict, the satisfaction of basic needs, the work meaningfulness and work engagement, patient care, pandemic stress and burnout.

Methods

This cross-sectional study is based on an online snowball sampling of 738 health workers from 27 hospitals. Panel research is limited to a maximum of 61 respondents for two successive waves. The analytical part is built on means comparison of analysed variables between all five pandemic waves and an in-depth model to explain the relationships between the variables.

Results

The results indicate statistically significant correlations between the perception of health risks and all selected factors excluding patient care, which seems to be above the own health perception. The factors’ dynamics was followed along all five pandemic waves. The developed model identified that one’s health status satisfaction is a mediator of the family–work conflict and, together, of work engagement. In turn, work engagement plays a significant role in satisfying basic psychological needs and supporting work meaningfulness. Also, work meaningfulness influences the satisfaction of basic psychological needs.

Discussion

Health workers with higher levels of positive perceived health are better at managing pandemic stress, burnout effects and work-family imbalances. Adaptive behaviors and attitudes towards COVID-19 pandemic threats could be identified in later pandemic waves due to the progress in terms of medical protocols and procedures.
Waiting for a digital therapist: three challenges on the path to psychotherapy delivered by artificial intelligence
Authors: Grodniewicz J. P. , Hohol Mateusz
Published: June 2023

Growing demand for broadly accessible mental health care, together with the rapid development of new technologies, trigger discussions about the feasibility of psychotherapeutic interventions based on interactions with Conversational Artificial Intelligence (CAI). Many authors argue that while currently available CAI can be a useful supplement for human-delivered psychotherapy, it is not yet capable of delivering fully fledged psychotherapy on its own. The goal of this paper is to investigate what are the most important obstacles on our way to developing CAI systems capable of delivering psychotherapy in the future. To this end, we formulate and discuss three challenges central to this quest. Firstly, we might not be able to develop effective AI-based psychotherapy unless we deepen our understanding of what makes human-delivered psychotherapy effective. Secondly, assuming that it requires building a therapeutic relationship, it is not clear whether psychotherapy can be delivered by non-human agents. Thirdly, conducting psychotherapy might be a problem too complicated for narrow AI, i.e., AI proficient in dealing with only relatively simple and well-delineated tasks. If this is the case, we should not expect CAI to be capable of delivering fully-fledged psychotherapy until the so-called “general” or “human-like” AI is developed. While we believe that all these challenges can ultimately be overcome, we think that being mindful of them is crucial to ensure well-balanced and steady progress on our path to AI-based psychotherapy.