bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial and auditory factors that influence successful music-based auditory training in pediatric cochlear implant recipients
Authors: Gfeller Kate , Mallalieu Ruth
Published: December 2023

Introduction

Cochlear implants (CIs), which are designed to support spoken communication of persons with severe to profound hearing loss, can provide improved hearing capability through passive exposure. However, auditory training may optimize perception of spectrally complex sounds such as music or speech. Reviews of music-based training for pediatric CI users have reported modest though variable benefits, as well as problems with attrition. It is presumed that more substantial changes may result from longer, more intensive training; however, the development of protocols sufficiently motivating for sustained intensity is challenging. This article examined the experiences of star pediatric CI users, whose years of music training have yielded exceptional auditory benefits. Greater understanding of their experiences and attitudes may suggest best practices for music-based training. Research aims included: (a) characterizing the musical behaviors and perceptual learning processes of music-centric (Music-centric, for purposes of this paper, refers to CI users who engage in sustained and successful music making such as music lessons and ensembles and focused music listening over a period of years, and who derive deep satisfaction from those experiences.) pediatric CI users, and (b) identifying psychosocial and auditory factors that motivated persistence in auditory training.

Methods

We used qualitative and patient-engaged research methodologies, gathering data through questionnaires with open-ended questions. The participants, six music-centric CI users and five parents, described their experiences and attitudes regarding music training, and factors that supported or undermined those experiences. Data were analyzed using reflexive thematic analysis.

Results

The codes were consolidated into five themes and organized into a Model of Music-Based Learning for Pediatric Cochlear Implant Recipients. Sustained participation in music training was perceived as a dynamic process including varied musical stimuli, and moderated by intrinsic (attitude, perceived behavioral control) and extrinsic (parents, teachers, peers) influences, hearing status, sound access and background factors.

Discussion

These themes highlighted motivational factors that pediatric CI users and parents considered important to sustained, intensive and successful music learning throughout childhood and adolescence. These factors should be considered in the development of music-based training for pediatric CI recipients.
Comparisons of air-conduction hearing thresholds between manual and automated methods in a commercial audiometer
Authors: Liu Hui , Fu Xinxing , Li Mohan , Wang Shuo
Published: December 2023

Objective

To investigate the correlation of air-conduction thresholds between automated audiometry in a non-isolated environment and manual audiometry in participants with normal hearing and different degrees of hearing loss.

Methods

Eighty-three participants aged 11–88 years old underwent automated pure-tone audiometry in a non-acoustically isolated environment, and the results were compared with those of manual pure-tone audiometry performed in a standard acoustically isolated booth, with the order of testing randomised. Six frequencies of 250, 500, 1,000, 2000, 4,000 and 8,000 Hz were tested.

Results

All 166 ears were completed and 996 valid hearing threshold data were obtained, with 28 data exceeding the 95% confidence interval in the Bland–Altman plot, accounting for 2.81% of all data. The means and standard deviations of the differences for the six frequencies from 250 to 8,000 Hz were, respectively, 0.63 ± 5.31, 0.69 ± 4.50, 0.45 ± 4.99, 0.3 ± 6.2, −0.15 ± 4.8, and 0.21 ± 4.97 dB. The correlation coefficients of the two test results for normal hearing, mild, moderate, severe and above hearing loss groups were 0.95, 0.92, 0.97, and 0.96, respectively. The correlation coefficient of the automated and manual audiometry thresholds for the age groups under 40 years, 40–60 years, and 60 years above, were 0.98, 0.97 and 0.97, respectively, with all being statistically significant (p < 0.01). The response time of the three age groups were 791 ± 181 ms, 900 ± 190 ms and 1,063 ± 332 ms, respectively, and there was a significant difference between the groups under 40 years and over 60 years.

Conclusion

There was good consistency between automated pure-tone audiometry in a non-acoustically isolated environment and manual pure-tone audiometry in participants with different hearing levels and different age groups.
Increased fiber density of the fornix in patients with chronic tinnitus revealed by diffusion-weighted MRI
Authors: Rosemann Stephanie , Rauschecker Josef P.
Published: December 2023

Up to 45% of the elderly population suffer from chronic tinnitus - the phantom perception of sound that is often perceived as ringing, whistling, or hissing “in the ear” without external stimulation. Previous research investigated white matter changes in tinnitus patients using diffusion-weighted magnetic resonance imaging (DWI) to assess measures such as fractional anisotropy (a measure of microstructural integrity of fiber tracts) or mean diffusivity (a measure for general water diffusion). However, findings overlap only minimally and are sometimes even contradictory. We here present the first study encompassing higher diffusion data that allow to focus on changes in tissue microstructure, such as number of axons (fiber density) and macroscopic alterations, including axon diameter, and a combination of both. In order to deal with the crossing-fibers problem, we applied a fixel-based analysis using a constrained spherical deconvolution signal modeling approach. We investigated differences between tinnitus patients and control participants as well as how cognitive abilities and tinnitus distress are related to changes in white matter morphology in chronic tinnitus. For that aim, 20 tinnitus patients and 20 control participants, matched in age, sex and whether they had hearing loss or not, underwent DWI, audiometric and cognitive assessments, and filled in questionnaires targeting anxiety and depression. Our results showed increased fiber density in the fornix in tinnitus patients compared to control participants. The observed changes might, reflect compensatory structural alterations related to the processing of negative emotions or maladaptive changes related to the reinforced learning of the chronic tinnitus sensation. Due to the low sample size, the study should be seen as a pilot study that motivates further research to investigate underlying white matter morphology alterations in tinnitus.
Postsynaptic dorsal column pathway activation during spinal cord stimulation in patients with chronic pain
Authors: Gmel Gerrit Eduard , Santos Escapa Rosana , Benkohen Teddy Edmond , Mugan Dave , Parker John Louis , Palmisani Stefano
Published: December 2023

Spinal cord stimulation (SCS) treatment for chronic pain relies on the activation of primary sensory fibres ascending to the brain in the dorsal columns. While the efficacy of SCS has been demonstrated, the precise mechanism of action and nature of the fibres activated by stimulation remain largely unexplored. Our investigation in humans with chronic neuropathic pain undergoing SCS therapy, found that post-synaptic dorsal column (PSDC) fibres can be activated synaptically by the primary afferents recruited by stimulation, and axonically by the stimulation pulses directly. Synaptic activation occurred in 9 of the 14 patients analysed and depended on the vertebral level of stimulation. A clear difference in conduction velocities between the primary afferents and the PSDC fibres were observed. Identification of PSDC fibre activation in humans emphasises the need for further investigation into the role they play in pain relief and the sensory response sensation (paraesthesia) experienced by patients undergoing SCS.
A latent code based multi-variable modulation network for susceptibility mapping
Authors: Zhou Weibin , Xi Jiaxiu , Bao Lijun
Published: December 2023

Quantitative susceptibility mapping (QSM) is a technique for obtaining quantitative information on tissue susceptibility and has shown promising potential for clinical applications, in which the magnetic susceptibility is calculated by solving an ill-posed inverse problem. Recently, deep learning-based methods are proposed to address this issue, but the diversity of data distribution was not well considered, and thus the model generalization is limited in clinical applications. In this paper, we propose a Latent Code based Multi-Variable modulation network for QSM reconstruction (LCMnet). Particularly, a specific modulation module is exploited to incorporate three variables, i.e., field map, magnitude image, and initial susceptibility. The latent code in the modulated convolution is learned from feature maps of the field data using the encoder-decoder framework. The susceptibility map pre-estimated from simple thresholding is the constant input of the module, thereby enhancing the network stability and accelerating training convergence. As another input, multi-level features generated by a cross-fusion block integrate the information of field and magnitude data effectively. Experimental results on in vivo human brain data, challenge data, clinical data and synthetic data demonstrate that the proposed method LCMnet can achieve outstanding performance on accurate susceptibility measurement and also excellent generalization.
Fundamental roles of the Optineurin gene in the molecular pathology of Amyotrophic Lateral Sclerosis
Authors: Zhao Shumin , Chen Ranran , Gao Ying , Lu Yanchao , Bai Xue , Zhang Jingjing
Published: December 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) in the brain and spinal cord. It is caused by multiple factors, including mutations in any one of several specific genes. Optineurin (OPTN) mutation is an essential cause of some familial and sporadic ALS. Besides, as a multifunctional protein, OPTN is highly expressed and conserved in the central nervous system. OPTN exerts its functions by interacting with various proteins, often acting as an adaptor to provide a link between two or more core proteins related to autophagy and inflammation, etc. OPTN mutation mainly results in its function deficiency, which alters these interactions, leading to functional impairment in many processes. Meanwhile, OPTN immunopositive inclusions are also confirmed in the cases of ALS due to C9ORF72, FUS, TARDBP, and SOD1 mutations. Therefore, OPTN gene may play fundamental roles in the molecular pathology of ALS in addition to OPTN mutation. In this review, we summarize the recent advances in the ALS pathology of OPTN defect, such as mitophagy disorder, neuroinflammation, neuronal axonal degeneration, vesicular transport dysfunction, etc., which will provide a reference for research on the pathogenesis and treatment of ALS.
Realizing asynchronous finite-time robust tracking control of switched flight vehicles by using nonfragile deep reinforcement learning
Authors: Cheng Haoyu , Song Ruijia , Li Haoran , Wei Wencheng , Zheng Biyu , Fang Yangwang
Published: December 2023

In this study, a novel nonfragile deep reinforcement learning (DRL) method was proposed to realize the finite-time control of switched unmanned flight vehicles. Control accuracy, robustness, and intelligence were enhanced in the proposed control scheme by combining conventional robust control and DRL characteristics. In the proposed control strategy, the tracking controller consists of a dynamics-based controller and a learning-based controller. The conventional robust control approach for the nominal system was used for realizing a dynamics-based baseline tracking controller. The learning-based controller based on DRL was developed to compensate model uncertainties and enhance transient control accuracy. The multiple Lyapunov function approach and mode-dependent average dwell time approach were combined to analyze the finite-time stability of flight vehicles with asynchronous switching. The linear matrix inequalities technique was used to determine the solutions of dynamics-based controllers. Online optimization was formulated as a Markov decision process. The adaptive deep deterministic policy gradient algorithm was adopted to improve efficiency and convergence. In this algorithm, the actor–critic structure was used and adaptive hyperparameters were introduced. Unlike the conventional DRL algorithm, nonfragile control theory and adaptive reward function were used in the proposed algorithm to achieve excellent stability and training efficiency. We demonstrated the effectiveness of the presented algorithm through comparative simulations.
Changes in the urinary proteome of rats after short-term intake of magnesium L-threonate(MgT)
Authors: Shen Ziyun , Yang Minhui , Wang Haitong , Liu Yuqing , Gao Youhe
Published: December 2023

Introduction

Magnesium (Mg) is an important mineral in living organisms. Magnesium has multiple functions in the human body, wherein it plays an important therapeutic and preventive role in a variety of diseases.

Methods

Urine samples of rats before and after gavage of magnesium L-threonate (MgT) were collected, and the urinary proteome was identified using the LC-MS/MS technique and analyzed using various databases.

Results and discussion

The results illustrated that the urinary proteome of rats was significantly altered after short-term intake of magnesium supplements and that the differential proteins and the biological functions were related to magnesium. This study innovatively establishes a method to study nutrients from the perspective of urine proteomics. This work demonstrates that the urinary proteome is capable of reflecting the effects of nutrient intake on the organism in a more systematic and comprehensive manner and has the potential to provide clues for clinical nutrition research and practice.
27-hydroxycholesterol and DNA damage repair: implication in prostate cancer
Authors: Galvan Gloria Cecilia , Friedrich Nadine A. , Das Sanjay , Daniels James P. , Pollan Sara , Dambal Shweta , Suzuki Ryusuke , Sanders Sergio E. , You Sungyong , Tanaka Hisashi , Lee Yeon-Joo , Yuan Wei , de Bono Johann S. , Vasilevskaya Irina , Knudsen Karen E. , Freeman Michael R. , Freedland Stephen J.
Published: December 2023

Introduction

We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects.

Methods

We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment analysis was done using the GSEA software with hallmark gene sets from MSigDB. Key changes were validated at mRNA and protein levels. Human PC transcriptomes from six datasets were analyzed to determine the correlation between CYP27A1 and DNA repair gene expression signatures. DNA damage was assessed via comet assays.

Results

Transcriptome analysis revealed 27HC treatment downregulated Hallmark pathways related to DNA damage repair, decreased expression of FEN1 and RAD51, and induced “BRCAness” by downregulating genes involved in homologous recombination regulation in LNCaP cells. Consistently, we found a correlation between higher CYP27A1 expression (i.e., higher intracellular 27HC) and decreased expression of DNA repair gene signatures in castration-sensitive PC (CSPC) in human PC datasets. However, such correlation was less clear in metastatic castration-resistant PC (mCRPC). 27HC increased expression of DNA damage repair markers in PC cells, notably in AR+ cells, but no consistent effects in AR- cells and decreased expression in non-neoplastic prostate epithelial cells. While testing the clinical implications of this, we noted that 27HC treatment increased DNA damage in LNCaP cells via comet assays. Effects were reversible by adding back cholesterol, but not androgens. Finally, in combination with olaparib, a PARP inhibitor, we showed additive DNA damage effects.

Discussion

These results suggest 27HC induces “BRCAness”, a functional state thought to increase sensitivity to PARP inhibitors, and leads to increased DNA damage, especially in CSPC. Given the emerging appreciation that defective DNA damage repair can drive PC growth, future studies are needed to test whether 27HC creates a synthetic lethality to PARP inhibitors and DNA damaging agents in CSPC.
Use of PIRADS 2.1 to predict capsular invasion in patients with radiologic T3a prostate cancer
Authors: Song Wan , Ko Kwang Jin , Lee Jae Kyung , Kang Minyong , Sung Hyun Hwan , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong IL. , Jeon Seong Soo , Chung Jae Hoon
Published: December 2023

Objective

Using multi-parametric magnetic resonance imaging (mpMRI) to identify patients with clinical T3a (cT3a) who were overestimated on mpMRI with final pathological T2 (pT2). To suggest that the neurovascular bundle (NVB) can be preserved by evaluating the characteristics of patients according to their pathological grade among cT3a prostate cancer (PCa) patients using mpMRI.

Materials and methods

Patients who underwent robot-assisted laparoscopic radical prostatectomy (RALP) were retrospectively analyzed and those patients with clinical T3aN0M0 were enrolled. These enrolled patients were divided into a localized cancer group with pT2 PCa and a locally advanced group with pT3a or higher. Factors affecting the diagnosis of localized PCa after RALP in patients with cT3a PCa were evaluated.

Results

Among the preoperative parameters of patients with cT3a PCa, the prostate specific antigen density (PSAD) (OR: 3.76, 95% CI: 1.85–7.64, p<0.001), international society of urological pathology (ISUP) grade (p<0.05), and index lesion size (OR: 1.44, 95% CI: 1.85–7.64, p<0.001) were significantly associated with pathological locally advanced PCa. Optimal cut-off values for prediction of pT3a or higher were 0.36 ng/mL2 for PSAD (sensitivity: 55.7%, specificity: 70.8%), 1.77 cm for index lesion size (sensitivity: 54.3%, specificity: 66.0%), and 2.5 for ISUP grading (sensitivity: 67.6%, specificity: 53.2%). For prediction of pT3a or higher among patients with cT3a PCa, a nomogram was developed using ISUP grade, index lesion size, and PSAD on prostate biopsy (area under the curve: 0.71, 95% CI: 0.670–0.754, p<0.001). PSAD less than 0.36 index lesion size less than 1.77 cm, and biopsy ISUP grade 1–2 are highly likely to indicate that there is no actual extracapsular extension in cT3a PCa patients.

Conclusions

PSAD, ISUP, and index lesion size showed significant associations with the classification of pathologic localized and locally advanced PCa in patients with cT3a PCa. A nomogram including these features can predict the diagnosis of locally advanced PCa in patients with cT3a PCa.
Viral oncogenes, viruses, and cancer: a third-generation sequencing perspective on viral integration into the human genome
Authors: Ye Ruichen , Wang Angelina , Bu Brady , Luo Pengxiang , Deng Wenjun , Zhang Xinyi , Yin Shanye
Published: December 2023

The link between viruses and cancer has intrigued scientists for decades. Certain viruses have been shown to be vital in the development of various cancers by integrating viral DNA into the host genome and activating viral oncogenes. These viruses include the Human Papillomavirus (HPV), Hepatitis B and C Viruses (HBV and HCV), Epstein-Barr Virus (EBV), and Human T-Cell Leukemia Virus (HTLV-1), which are all linked to the development of a myriad of human cancers. Third-generation sequencing technologies have revolutionized our ability to study viral integration events at unprecedented resolution in recent years. They offer long sequencing capabilities along with the ability to map viral integration sites, assess host gene expression, and track clonal evolution in cancer cells. Recently, researchers have been exploring the application of Oxford Nanopore Technologies (ONT) nanopore sequencing and Pacific BioSciences (PacBio) single-molecule real-time (SMRT) sequencing in cancer research. As viral integration is crucial to the development of cancer via viruses, third-generation sequencing would provide a novel approach to studying the relationship interlinking viral oncogenes, viruses, and cancer. This review article explores the molecular mechanisms underlying viral oncogenesis, the role of viruses in cancer development, and the impact of third-generation sequencing on our understanding of viral integration into the human genome.
Diffusion MRI correlation with p16 status and prediction for tumor progression in locally advanced head and neck cancer
Authors: Cao Yue , Aryal M. , Li P. , Lee C. , Schipper M. , You D. , Jaworski E. , Gharzai L. , Shah J. , Eisbruch A. , Mierzwa Michelle
Published: December 2023

Purpose

To investigate p16 effects on diffusion image metrics and associations with tumor progression in patients with locally advanced head and neck cancers.

Methods

Diffusion images pretreatment and after 20 Gy (2wk) of RT were analyzed in patients with cT4/N3 p16+ oropharynx cancer (OPSCC) (N=51) and locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) (N=28), enrolled onto a prospective adaptive RT trial. Mean ADC values, subvolumes with ADC <1.2 um2/ms (TVLADC), and peak values of low (µL) and high (µH) components of ADC histograms in primary and total nodal gross tumor volumes were analyzed for prediction of freedom from local, distant, or any progression (FFLP, FFDP or FFLRDP) using multivariate Cox proportional-hazards model with clinical factors. P value with false discovery control <0.05 was considered as significant.

Results

With a mean follow up of 36 months, 18 of LAHNSCC patients and 16 of p16+ OPSCC patients had progression. After adjusting for p16, small µL and ADC values, and large TVLADC of primary tumors pre-RT were significantly associated with superior FFLRDP, FFLP and FFDP in the LAHNSCC (p<0.05), but no diffusion metrics were significant in p16+ oropharynx cancers. Post ad hoc analysis of the p16+ OPSCC only showed that large TVLADC of the total nodal burden pre-RT was significantly associated with inferior FFDP (p=0.05).

Conclusion

ADC metrics were associated with different progression patterns in the LAHNSCC and p16+ OPSCC, possibly explained by differences in cancer biology and morphology. A deep understanding of ADC metrics is warranted to establish imaging biomarkers for adaptive RT in HNSCC.
Research hotspots and trends on neuropathic pain-related mood disorders: a bibliometric analysis from 2003 to 2023
Authors: Wang Xiaohua , Zhuang Yueyang , Lin Zhigang , Chen Shuijin , Chen Lechun , Huang Hongye , Lin Hui , Wu Shiye
Published: December 2023

Introduction

Neuropathic Pain (NP) is often accompanied by mood disorders, which seriously affect the quality of life of patients. This study aimed to analyze the hotspots and trends in NP-related mood disorder research using bibliometric methods and to provide valuable predictions for future research in this field.

Methods

Articles and review articles on NP-related mood disorders published from January 2003 to May 2023 were retrieved from the Web of Science Core Collection. We used CiteSpace to analyze publications, countries, institutions, authors, cited authors, journals, cited journals, references, cited references, and keywords. We also analyzed collaborative network maps and co-occurrence network maps.

Results

A total of 4,540 studies were collected for analysis. The number of publications concerning NP-related mood disorders every year shows an upward trend. The United States was a major contributor in this field. The University of Toronto was the most productive core institution. C GHELARDINI was the most prolific author, and RH DWORKIN was the most frequently cited author. PAIN was identified as the journal with the highest productivity and citation rate. The current research hotspots mainly included quality of life, efficacy, double-blind methodology, gabapentin, pregabalin, postherpetic neuralgia, and central sensitization. The frontiers in research mainly focused on the mechanisms associated with microglia activation, oxidative stress, neuroinflammation, and NP-related mood disorders.

Discussion

In conclusion, the present study provided insight into the current state and trends in NP-related mood disorder research over the past 20 years. Consequently, researchers will be able to identify new perspectives on potential collaborators and cooperative institutions, hot topics, and research frontiers in this field.
Association between mortality and critical events within 48 hours of transfer to the pediatric intensive care unit
Authors: Liang Huan , Carey Kyle A. , Jani Priti , Gilbert Emily R. , Afshar Majid , Sanchez-Pinto L. Nelson , Churpek Matthew M. , Mayampurath Anoop
Published: December 2023

Introduction

Critical deterioration in hospitalized children, defined as ward to pediatric intensive care unit (PICU) transfer followed by mechanical ventilation (MV) or vasoactive infusion (VI) within 12 h, has been used as a primary metric to evaluate the effectiveness of clinical interventions or quality improvement initiatives. We explore the association between critical events (CEs), i.e., MV or VI events, within the first 48 h of PICU transfer from the ward or emergency department (ED) and in-hospital mortality.

Methods

We conducted a retrospective study of a cohort of PICU transfers from the ward or the ED at two tertiary-care academic hospitals. We determined the association between mortality and occurrence of CEs within 48 h of PICU transfer after adjusting for age, gender, hospital, and prior comorbidities.

Results

Experiencing a CE within 48 h of PICU transfer was associated with an increased risk of mortality [OR 12.40 (95% CI: 8.12–19.23, P < 0.05)]. The increased risk of mortality was highest in the first 12 h [OR 11.32 (95% CI: 7.51–17.15, P < 0.05)] but persisted in the 12–48 h time interval [OR 2.84 (95% CI: 1.40–5.22, P < 0.05)]. Varying levels of risk were observed when considering ED or ward transfers only, when considering different age groups, and when considering individual 12-h time intervals.

Discussion

We demonstrate that occurrence of a CE within 48 h of PICU transfer was associated with mortality after adjusting for confounders. Studies focusing on the impact of quality improvement efforts may benefit from using CEs within 48 h of PICU transfer as an additional evaluation metric, provided these events could have been influenced by the initiative.
Methadone and neonatal abstinence syndrome (NAS): what we think we know, but do not
Authors: McCarthy John J. , Finnegan Loretta P.
Published: December 2023

Since the first use of methadone to treat OUD in pregnancy in the 1970s, there has been a long, controversial, and confusing history of studies, regulatory actions, and practice changes that have clouded an accurate perception of methadone's use in pregnancy. This review will trace this history with a focus on the effect of methadone exposure during pregnancy on neonatal abstinence syndrome (NAS). A new laboratory measure, the serum methadone/metabolite ratio (MMR), has provided a tool for documenting the profoundly dynamic nature of perinatal metabolism. Continuous induction of metabolic enzymes during pregnancy requires dose adjustments and dose frequency changes. The concept of “fetal methadone dosing” emphasizes that relative stability of methadone levels in the fetus is an important consideration for methadone dosing in pregnancy. Finally, the effects of the societal “war on drugs” on pediatric management of neonatal withdrawal risks will be discussed, as well as the importance of comprehensive services for mother and child including the “rooming-in” approach of neonatal care which has considerably replaced the older NICU care model of maternal/infant separation.
Case Report: Novel biallelic moderately damaging variants in RTTN in a patient with cerebellar dysplasia
Authors: Romano Ferruccio , Amadori Elisabetta , Madia Francesca , Severino Mariasavina , Capra Valeria , Rizzo Renata , Barone Rita , Corradi Beatrice , Maragliano Luca , Shams Nosrati Mohammad Sadegh , Falace Antonio , Striano Pasquale , Zara Federico , Scala Marcello
Published: December 2023

Rotatin, encoded by the RTTN gene, is a centrosomal protein with multiple, emerging functions, including left-right specification, ciliogenesis, and neuronal migration. Recessive variants in RTTN are associated with a neurodevelopmental disorder with microcephaly and malformations of cortical development known as “Microcephaly, short stature, and polymicrogyria with seizures” (MSSP, MIM #614833). Affected individuals show a wide spectrum of clinical manifestations like intellectual disability, poor/absent speech, short stature, microcephaly, and congenital malformations. Here, we report a subject showing a distinctive neuroradiological phenotype and harboring novel biallelic variants in RTTN: the c.5500A>G, p.(Asn1834Asp), (dbSNP: rs200169343, ClinVar ID:1438510) and c.19A>G, p.(Ile7Val), (dbSNP: rs201165599, ClinVar ID:1905275) variants. In particular brain magnetic resonance imaging (MRI) showed a peculiar pattern, with cerebellar hypo-dysplasia, and multiple arachnoid cysts in the lateral cerebello-medullary cisterns, in addition to left Meckel cave. Thus, we compare his phenotypic features with current literature, speculating a possible role of newly identified RTTN variants in his clinical picture, and supporting a relevant variability in this emerging condition.
Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B
Authors: Fan Hai-Na , Zhao Zhi-Min , Huang Kai , Wang Xiao-Ning , Dai Yun-Kai , Liu Cheng-Hai
Published: December 2023

Background and aims: The serum metabolites changes in patients with hepatitis B virus (HBV)-related cirrhosis as progression. Peroxisome proliferator-activated receptor gamma (PPARγ) is closely related to lipid metabolism in cirrhotic liver. However, the relationship between fatty acids and the expression of hepatic PPARγ during cirrhosis regression remains unknown. In this study, we explored the serum metabolic characteristics and expression of PPARγ in patients with histological response to treatment with entecavir.

Methods: Sixty patients with HBV-related cirrhosis were selected as the training cohort with thirty patients each in the regression (R) group and non-regression (NR) group based on their pathological changes after 48-week treatment with entecavir. Another 72 patients with HBV-related cirrhosis and treated with entecavir were collected as the validation cohort. All of the serum samples were tested using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Data were processed through principal component analysis and orthogonal partial least square discriminant analysis. Hepatic PPARγ expression was observed using immunohistochemistry. The relationship between serum fatty acids and PPARγ was calculated using Pearson’s or Spearman’s correlation analysis.

Results: A total of 189 metabolites were identified and 13 differential metabolites were screened. Compared to the non-regression group, the serum level of fatty acids was higher in the R group. At baseline, the expression of PPARγ in hepatic stellate cells was positively correlated with adrenic acid (r2 = 0.451, p = 0.046). The expression of PPARγ in both groups increased after treatment, and the expression of PPARγ in the R group was restored in HSCs much more than that in the NR group (p = 0.042). The adrenic acid and arachidonic acid (AA) in the R group also upgraded more than the NR group after treatment (p = 0.037 and 0.014).

Conclusion: Baseline serum differential metabolites, especially fatty acids, were identified in patients with HBV-related cirrhosis patients who achieved cirrhosis regression. Upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPARγ in HSCs may play a crucial role in liver fibrosis improvement.
Prophylactic treatments for vestibular migraine: a systematic review and network meta-analysis of randomized clinical trials
Authors: Chu Hongyuan , Wang Yuru , Ling Xia , Li Kangzhi , Yang Xu
Published: December 2023

Objectives: We compared and ranked the efficacy and tolerability of multiple prophylactic treatments for vestibular migraine (VM), including β-blockers, calcium channel blockers, antiseizure medications, and antidepressants such as tricyclics and serotonin–noradrenaline reuptake inhibitors.

Methods: PubMed, Web of Science, Embase, and Cochrane Center for Clinical Trials were systematically searched for relevant randomized clinical trials (RCTs) from March 2023 to May 2023. Studies on the efficacy and tolerability of prophylactic treatments for VM were included. Efficacy was measured using the average vertigo frequency per month and dizziness handicap inventory (DHI) improvement after 3–6 months of treatment. Tolerability was measured by the number of patients reporting at least one adverse event (AE). Network meta-analyses were performed according to a Bayesian framework and a random-effects model based on odds ratios or mean differences (MDs) and 95% confidence intervals (CIs). A sequence of ranking probability was calculated according to the surface under the cumulative ranking (SUCRA) curve. This network meta-analysis was previously registered with PROSPERO (CRD42023422258).

Results: Five RCTs comprising 334 patients were analyzed by synthesizing the published evidence. Considering the examined prophylactic therapies, there is significant evidence that valproate acid (VPA) is superior to placebo or abortive treatment alone (MD = −4.12, 95% CI = −8.09, −0.15) in reducing the frequency of vertigo. Flunarizine (MD = 20.00, 95% CI = 10.90, 29.10), valproate acid (MD = 18.88, 95% CI = 10.42, 27.34), and venlafaxine (MD = 11.48, 95% CI = 9.84, 13.12) were significantly more effective than placebo or abortive treatment in reducing DHI. VPA most strongly reduced the frequency of vertigo according to SUCRA, but it ranked third-to-last in tolerability. Flunarizine ranked best in DHI improvement but worst in tolerability. Metoprolol ranked worst for efficacy but best for tolerability.

Conclusion: VPA and flunarizine reduced the frequency of vertigo and improved DHI, but they had unfavorable tolerability. The effects of metoprolol on vertigo require further study. Given the low certainty and limited sample, additional head-to-head RCTs are warranted to further confirm efficacy.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/; Identifier CRD42023422258.
X-ray detector requirements for laser–plasma accelerators
Authors: Armstrong Chris D. , Scott G. G. , Richards S. , Patel J. K. , Fedorov K. , Gray R. J. , Welsby K. , Rajeev P. P.
Published: December 2023

Laser–plasma interactions (LPIs) are an emerging source of a range of energetic radiation. LPI experiments drive ultra-short (< ps) and brilliant sources of X-rays from keV to MeV energies. Designing detectors to maximise the sensitivity and resolution achievable with these sources is paramount to optimising laser-driven accelerators. In this article, we explore the key parameters associated with laser-driven X-ray sources and the detector systems required to characterise them. We present a concise approach to modelling the sensitivity and resolution for indirect detector systems factoring in both the optical collection and the X-ray attenuation within the scintillator.
Metabolome combined with transcriptome profiling reveals the dynamic changes in flavonoids in red and green leaves of Populus × euramericana ‘Zhonghuahongye’
Authors: Yang Yun , Chen Mengjiao , Zhang Wan , Zhu Haiyang , Li Hui , Niu Xinjiang , Zhou Zongshun , Hou Xiaoya , Zhu Jingle
Published: December 2023

Flavonoids are secondary metabolites that have economic value and are essential for health. Poplar is a model perennial woody tree that is often used to study the regulatory mechanisms of flavonoid synthesis. We used a poplar bud mutant, the red leaf poplar variety 2025 (Populus × euramericana ‘Zhonghuahongye’), and green leaves as study materials and selected three stages of leaf color changes for evaluation. Phenotypic and biochemical analyses showed that the total flavonoid, polyphenol, and anthocyanin contents of red leaves were higher than those of green leaves in the first stage, and the young and tender leaves of the red leaf variety had higher antioxidant activity. The analyses of widely targeted metabolites identified a total of 273 flavonoid metabolites (114 flavones, 41 flavonols, 34 flavonoids, 25 flavanones, 21 anthocyanins, 18 polyphenols, 15 isoflavones, and 5 proanthocyanidins). The greatest difference among the metabolites was found in the first stage. Most flavonoids accumulated in red leaves, and eight anthocyanin compounds contributed to red leaf coloration. A comprehensive metabolomic analysis based on RNA-seq showed that most genes in the flavonoid and anthocyanin biosynthetic pathways were differentially expressed in the two types of leaves. The flavonoid synthesis genes CHS (chalcone synthase gene), FLS (flavonol synthase gene), ANS (anthocyanidin synthase gene), and proanthocyanidin synthesis gene LAR (leucoanthocyanidin reductase gene) might play key roles in the differences in flavonoid metabolism. A correlation analysis of core metabolites and genes revealed several candidate regulators of flavonoid and anthocyanin biosynthesis, including five MYB (MYB domain), three bHLH (basic helix-loop-helix), and HY5 (elongated hypocotyl 5) transcription factors. This study provides a reference for the identification and utilization of flavonoid bioactive components in red-leaf poplar and improves the understanding of the differences in metabolism and gene expression between red and green leaves at different developmental stages.
Design and test of Kinect-based variable spraying control system for orchards
Authors: Xue Xiuyun , Luo Qin , Ji Yihang , Ma Zhaoyong , Zhu Jiani , Li Zhen , Lyu Shilei , Sun Daozong , Song Shuran
Published: December 2023

Target detection technology and variable-rate spraying technology are key technologies for achieving precise and efficient pesticide application. To address the issues of low efficiency and high working environment requirements in detecting tree information during variable spraying in orchards, this study has designed a variable spraying control system. The system employed a Kinect sensor to real-time detect the canopy volume of citrus trees and adjusted the duty cycle of solenoid valves by pulse width modulation to control the pesticide application. A canopy volume calculation method was proposed, and precision tests for volume detection were conducted, with a maximum relative error of 10.54% compared to manual measurements. A nozzle flow model was designed to determine the spray decision coefficient. When the duty cycle ranged from 30% to 90%, the correlation coefficient of the flow model exceeded 0.95, and the actual flow rate of the system was similar to the theoretical flow rate. Field experiments were conducted to evaluate the spraying effectiveness of the variable spraying control system based on the Kinect sensor. The experimental results indicated that the variable spraying control system demonstrated good consistency between the theoretical spray volume and the actual spray volume. In deposition tests, compared to constant-rate spraying, the droplets under the variable-rate mode based on canopy volume exhibited higher deposition density. Although the amount of droplet deposit and coverage slightly decreased, they still met the requirements for spraying operation quality. Additionally, the variable-rate spray mode achieved the goal of reducing pesticide use, with a maximum pesticide saving rate of 57.14%. This study demonstrates the feasibility of the Kinect sensor in guiding spraying operations and provides a reference for their application in plant protection operations.
A complex regulatory network governs the expression of symbiotic genes in Sinorhizobium fredii HH103
Authors: Navarro-Gómez Pilar , Fuentes-Romero Francisco , Pérez-Montaño Francisco , Jiménez-Guerrero Irene , Alías-Villegas Cynthia , Ayala-García Paula , Almozara Andrés , Medina Carlos , Ollero Francisco-Javier , Rodríguez-Carvajal Miguel-Ángel , Ruiz-Sainz José-Enrique , López-Baena Francisco-Javier , Vinardell José-María , Acosta-Jurado Sebastián
Published: December 2023

Introduction

The establishment of the rhizobium-legume nitrogen-fixing symbiosis relies on the interchange of molecular signals between the two symbionts. We have previously studied by RNA-seq the effect of the symbiotic regulators NodD1, SyrM, and TtsI on the expression of the symbiotic genes (the nod regulon) of Sinorhizobium fredii HH103 upon treatment with the isoflavone genistein. In this work we have further investigated this regulatory network by incorporating new RNA-seq data of HH103 mutants in two other regulatory genes, nodD2 and nolR. Both genes code for global regulators with a predominant repressor effect on the nod regulon, although NodD2 acts as an activator of a small number of HH103 symbiotic genes.

Methods

By combining RNA-seq data, qPCR experiments, and b-galactosidase assays of HH103 mutants harbouring a lacZ gene inserted into a regulatory gene, we have analysed the regulatory relations between the nodD1, nodD2, nolR, syrM, and ttsI genes, confirming previous data and discovering previously unknown relations.

Results and discussion

Previously we showed that HH103 mutants in the nodD2, nolR, syrM, or ttsI genes gain effective nodulation with Lotus japonicus, a model legume, although with different symbiotic performances. Here we show that the combinations of mutations in these genes led, in most cases, to a decrease in symbiotic effectiveness, although all of them retained the ability to induce the formation of nitrogen-fixing nodules. In fact, the nodD2, nolR, and syrM single and double mutants share a set of Nod factors, either overproduced by them or not generated by the wild-type strain, that might be responsible for gaining effective nodulation with L. japonicus.
Exogenous abscisic acid and sugar induce a cascade of ripening events associated with anthocyanin accumulation in cultured Pinot Noir grape berries
Authors: Bennett Jeffrey , Meiyalaghan Sathiyamoorthy , Nguyen Han M. , Boldingh Helen , Cooney Janine , Elborough Caitlin , Araujo Leandro Dias , Barrell Philippa , Lin-Wang Kui , Plunkett Blue J. , Martin Damian , Espley Richard V.
Published: December 2023

Fruit quality is dependent on various factors including flavour, texture and colour. These factors are determined by the ripening process, either climacteric or non-climacteric. In grape berry, which is non-climacteric, the process is signalled by a complex set of hormone changes. Abscisic acid (ABA) is one of the key hormones involved in ripening, while sugar availability also plays a significant role in certain ripening aspects such as anthocyanin production. To understand the relative influence of hormone and sugar signalling in situ can prove problematic due to the physiological and environmental (abiotic and biotic) factors at play in vineyards. Here we report on the use of in vitro detached berry culture to investigate the comparative significance of ABA and sugar in the regulation of Pinot noir berry anthocyanin production under controlled conditions. Using a factorial experimental design, pre-véraison berries were cultured on media with various concentrations of sucrose and ABA. After 15 days of in vitro culture, the berries were analysed for changes in metabolites, hormones and gene expression. Results illustrated a stimulatory effect of sucrose and ABA on enhancing berry colour and a corresponding increase in anthocyanins. Increased ABA concentration was able to boost anthocyanin production in berries when sucrose supply was low. The sucrose and ABA effects on berry anthocyanins were primarily manifested through the up-regulation of transcription factors and other genes in the phenylpropanoid pathway, while in other parts of the pathway a down-regulation of key proanthocyanindin transcription factors and genes corresponded to sharp reduction in berry proanthocyanidins, irrespective of sucrose supply. Similarly, increased ABA was correlated with a significant reduction in berry malic acid and associated regulatory genes. These findings suggest a predominance of berry ABA over berry sugar in coordinating the physiological and genetic regulation of anthocyanins and proanthocyanins in Pinot noir grape berries.
The concept of “Work-Life-Blending”: a systematic review
Authors: Steffens Katharina , Sutter Christine , Sülzenbrück Sandra
Published: December 2023

Work-Life Blending refers to the permeability and dissolution of boundaries between work and personal life, bringing these domains closer together. However, a comprehensive, holistic definition or conceptualisation of Work-Life-Blending is currently lacking. This research aims to address this gap by conducting a systematic literature review to define and clarify the concept. The primary objective is to identify the key factors and dimensions of Work-Life-Blending by reviewing the current state of research, and by offering a clear and precise conceptual framework to guide further research in developing measurable and concrete concepts. We conducted a systematic review following the PRISMA guidelines to achieve this, drawing on keyword-based searches. We searched for English or German manuscripts in the electronic databases Business Source Premier and PsycARTICLES, using keywords such as “blending,” “blurring,” “fusion,” “Entgrenzung,” “Verschmelzung,” “Vermischung,” “boundary,” “border,” or “demarcation” in combination with “work” and “life.” From 1,400 screened references between 2000 and 2023, we identified 302 eligible articles. After applying exclusion criteria, 51 records were retained. Employing a holistic approach, we developed a coding scheme to analyse the articles focusing on antecedents, processes, and outcomes of Work-Life-Blending. Articles were prioritized based on their impact, relevance, and data content. Our analysis revealed a diverse field, and we adopted Clark’s central concepts (2000) to categorize Work-Life Blending into four key areas: Domains, Borders, Individual, and Interindividual. Structural analysis allowed us to gain deeper insights into the multifaceted nature of the research field. Diversification was evident in studies exploring various aspects, such as the combination of dimensions (e.g., organizational and individual factors), correlations between factors (e.g., working conditions), and the introduction of new constructs (e.g., motivational processes). Our research addresses a significant knowledge gap in the field of Work-Life-Blending, making valuable contributions to the existing body of knowledge. By examining key categories and proposing an extended definition, this study provides a robust foundation for further investigations. As a result, we established a classification of the determinants. Given the high degree of diversification, we offer a comprehensive framework for future research, contributing to a deeper understanding of Work-Life Blending.