bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteolysis of CD44 at the cell surface controls a downstream protease network
Authors: Wöhner Birte , Li Wenjia , Hey Sven , Drobny Alice , Werny Ludwig , Becker-Pauly Christoph , Lucius Ralph , Zunke Friederike , Linder Stefan , Arnold Philipp
Published: February 2023

The cell surface receptor cluster of differentiation 44 (CD44) is the main hyaluronan receptor of the human body. At the cell surface, it can be proteolytically processed by different proteases and was shown to interact with different matrix metalloproteinases. Upon proteolytic processing of CD44 and generation of a C-terminal fragment (CTF), an intracellular domain (ICD) is released after intramembranous cleavage by the γ-secretase complex. This intracellular domain then translocates to the nucleus and induces transcriptional activation of target genes. In the past CD44 was identified as a risk gene for different tumor entities and a switch in CD44 isoform expression towards isoform CD44s associates with epithelial to mesenchymal transition (EMT) and cancer cell invasion. Here, we introduce meprin β as a new sheddase of CD44 and use a CRISPR/Cas9 approach to deplete CD44 and its sheddases ADAM10 and MMP14 in HeLa cells. We here identify a regulatory loop at the transcriptional level between ADAM10, CD44, MMP14 and MMP2. We show that this interplay is not only present in our cell model, but also across different human tissues as deduced from GTEx (Gene Tissue Expression) data. Furthermore, we identify a close relation between CD44 and MMP14 that is also reflected in functional assays for cell proliferation, spheroid formation, migration and adhesion.
Preliminary insights on the metabolomics of Trichinella zimbabwensis infection in Sprague Dawley rats using GCxGC-TOF-MS (untargeted approach)
Authors: Ndlovu I. S. , Silas Ekuyikeno , Tshilwane S. I. , Chaisi M. , Vosloo A. , Mukaratirwa S.
Published: February 2023

Trichinella infections have been documented globally and have been detected in wild and/or domestic animals except Antarctica. There is paucity of information in the metabolic responses of hosts during Trichinella infections and biomarkers for infection that can be used in the diagnosis of the disease. The current study aimed to apply a non-targeted metabolomic approach to identify Trichinella zimbabwensis biomarkers including metabolic response from sera of infected Sprague-Dawley rats. Fifty-four male Sprague-Dawley rats were randomly assigned into T. zimbabwensis infected group (n = 36) and the non-infected control (n = 18). Results from the study showed that the metabolic signature of T. zimbabwensis infection consists of enriched methyl histidine metabolism, disturbance of the liver urea cycle, impeded TCA cycle, and upregulation of gluconeogenesis metabolism. The observed disturbance in the metabolic pathways was attributed to the effects caused by the parasite during its migration to the muscles resulting in downregulation of amino acids intermediates in the Trichinella-infected animals, and therefore affecting energy production and degradation of biomolecules. It was concluded that T. zimbabwensis infection caused an upregulation of amino acids; pipecolic acid, histidine, and urea, and upregulation of glucose and meso-Erythritol. Moreover, T. zimbabwensis infection caused upregulation of the fatty acids, retinoic acid, and acetic acid. These findings highlight the potential of metabolomics as a novel approach for fundamental investigations of host-pathogen interactions as well as for disease progression and prognosis.
Experience and perception of utilizing virtual clinic in neurological assessment in Saudi Arabia
Authors: Hmoud Mohammed , Salamatullah Hassan K. , Faidah Dania E. , Makkawi Seraj
Published: February 2023

Introduction

The World Health Organization defined electronic health as “the unified usage of information technology and electronic communications in the health sector.” In the Kingdom of Saudi Arabia, outpatient encounters were largely shifted to virtual clinics due to the crisis caused by COVID-19. This study aimed to evaluate the neurology consultants', specialists', and residents' experience and perception of utilizing virtual services for neurological assessment in Saudi Arabia.

Methods

This cross-sectional study was conducted by sending an anonymous online survey to neurologists and neurology residents in Saudi Arabia. The survey was developed by the authors and contained three main sections: demographics, subspecialty and years of experience after residency, and virtual clinics during the coronavirus disease 2019 (COVID-19) pandemic.

Result

A total of 108 neurology-practicing physicians in Saudi Arabia responded to the survey. Overall, 75% experienced virtual clinics, and 61% of them used phones for consultation. In neurology clinical practice, there was a significant difference (P < 0.001) regarding the teleconsultations for follow-up patients compared to the newly referred patients, being more suitable for the follow-up cases. Additionally, most neurology practicing physicians showed more confidence in performing history-taking tasks virtually (82.4%) than in physical examination. However, it was found that consultants were significantly (P < 0.03) more confident to virtually perform the cranial nerve, motor, coordination, and extrapyramidal assessments than the neurology residents. Physicians deemed it more suitable to conduct teleconsultations for patients with headaches and epilepsy than for those with neuromuscular and demyelinating diseases/multiple sclerosis. Furthermore, they agreed that patients' experiences (55.6%) and physicians' acceptance (55.6%) were the two main limitations to implementing virtual clinics.

Discussion

This study revealed that neurologists were more confident in performing history-taking in virtual clinics than in physical exams. On the contrary, consultants were more confident in handling the physical examination virtually than the neurology residents. Moreover, the most accepted clinics to be handled electronically were the headache and epilepsy clinics in comparison to the other subspecialties, being mainly diagnosed using history. Further studies with larger sample sizes are warranted to observe the level of confidence in performing different duties in neurology virtual clinics.
Design and analysis of HSC-BPPV diagnostic maneuver based on virtual simulation
Authors: Li Yanjun , Yang Xiaokai
Published: February 2023

Background

The preferred supine roll test for the diagnosis of horizontal semicircular canal BPPV has several disadvantages, including difficulty in locating the affected ear, inconsistent nystagmus performance on repeated testing, and lack of a typical latency period, resulting in insensitive diagnosis.

Objectives

To investigate novel diagnostic techniques with more scientific design, more accessible application, and better diagnostic sensitivity and specificity.

Materials and methods

Based on clinical microscopic CT data, we created a virtual simulation model of BPPV using Unity software. The physical simulation of the traditional supine roll test was performed to observe and analyse the movement of the otoliths, whose initial position was the typical stable position. In addition, the normal vectors of the plane and crista ampullaris of the horizontal semicircular canal were measured using 3D Slicer software. Based on this, we analyzed the critical steps for designing diagnostic maneuvers for BPPV in the horizontal semicircular canal. For a more accurate diagnosis of horizontal semicircular canal BPPV, it is critical to rotate the horizontal semicircular canal to be parallel to gravity. It is also necessary to move the otolith by swinging the head. As a result, we developed two diagnostic maneuvers: the 60° roll test and the prone roll test. We also performed simulations to observe otolith movement and predict nystagmus performance.

Conclusions

The 60° roll test and the prone roll test can complement the supine roll test. Compared to the supine roll test, they not only effectively differentiate canalolithiasis from cupulolithiasis, but also make it easier to determine the position of the otoliths, and the characteristics of the nystagmus are more pronounced. Significant diagnostic features have significant potential benefits for home and telemedicine.
RETRACTED: NeuroSuites: An online platform for running neuroscience, statistical, and machine learning tools
Authors: Moreno-Rodríguez José Luis , Larrañaga Pedro , Bielza Concha
Published: February 2023

Nowadays, an enormous amount of high dimensional data is available in the field of neuroscience. Handling these data is complex and requires the use of efficient tools to transform them into useful knowledge. In this work we present NeuroSuites, an easy-access web platform with its own architecture. We compare our platform with other software currently available, highlighting its main strengths. Thanks to its defined architecture, it is able to handle large-scale problems common in some neuroscience fields. NeuroSuites has different neuroscience-oriented applications and tools to integrate statistical data analysis and machine learning algorithms commonly used in this field. As future work, we want to further expand the list of available software tools as well as improve the platform interface according to user demands.
Prenatal alcohol exposure results in brain region- and sex-specific changes in circHomer1 expression in adult mouse brain
Authors: Papageorgiou Grigorios , Amoah Stephen K. , Pierotti Caroline , Otero Madison , Eckel Sophie , Coffey Kacie , Allan Andrea M. , Caldwell Kevin K. , Mellios Nikolaos
Published: February 2023

Circular RNAs (circRNAs) are a novel category of covalently-closed non-coding RNAs mainly derived from the back-splicing of exons or introns of protein-coding genes. In addition to their inherent high overall stability, circRNAs, have been shown to have strong functional effects on gene expression via a multitude of transcriptional and post-transcriptional mechanisms. Furthermore, circRNAs, appear to be particularly enriched in the brain and able to influence both prenatal development and postnatal brain function. However, little is known about the potential involvement of circRNAs in the long term influence of prenatal alcohol exposure (PAE) in the brain and their relevance for Fetal Alcohol Spectrum Disorders (FASD). Using circRNA-specific quantification, we have found that circHomer1, an activity-dependent circRNA derived from Homer protein homolog 1 (Homer1) and enriched in postnatal brain, is significantly down-regulated in the male frontal cortex and hippocampus of mice subjected to modest PAE. Our data further suggest that the expression of H19, an imprinted embryonic brain-enriched long non-coding RNA (lncRNA), is significantly up-regulated in the frontal cortex of male PAE mice. Furthermore, we show opposing changes in the developmental- and brain region specific- expression of circHomer1 and H19. Lastly, we show that knockdown of H19 results in robust increases in circHomer1 but not linear HOMER1 mRNA expression in human glioblastoma cell lines. Taken together, our work uncovers notable sex- and brain region-specific alterations in circRNA and lncRNA expression following PAE and introduces novel mechanistic insights with potential relevance to FASD.
Emerging roles of miRNAs in neuropathic pain: From new findings to novel mechanisms
Authors: Zhao Yu-Ying , Wu Zi-Jun , Zhu Li-Juan , Niu Tong-Xiang , Liu Bin , Li Jing
Published: February 2023

Neuropathic pain, which results from damage to the somatosensory nervous system, is a global clinical condition that affects many people. Neuropathic pain imposes significant economic and public health burdens and is often difficult to manage because the underlying mechanisms remain unclear. However, mounting evidence indicates a role for neurogenic inflammation and neuroinflammation in pain pattern development. There is increasing evidence that the activation of neurogenic inflammation and neuroinflammation in the nervous system contribute to neuropathic pain. Altered miRNA expression profiles might be involved in the pathogenesis of both inflammatory and neuropathic pain by regulating neuroinflammation, nerve regeneration, and abnormal ion channel expression. However, the lack of knowledge about miRNA target genes prevents a full understanding of the biological functions of miRNAs. At the same time, an extensive study on exosomal miRNA, a newly discovered role, has advanced our understanding of the pathophysiology of neuropathic pain in recent years. This section provides a comprehensive overview of the current understanding of miRNA research and discusses the potential mechanisms of miRNAs in neuropathic pain.
Impact of feeding habits on the development of language-specific processing of phonemes in brain: An event-related potentials study
Authors: Alatorre-Cruz Graciela C. , Andres Aline , Gu Yuyuan , Downs Heather , Hagood Darcy , Sorensen Seth T. , Williams David Keith , Larson-Prior Linda J.
Published: February 2023

Introduction

Infancy is a stage characterized by multiple brain and cognitive changes. In a short time, infants must consolidate a new brain network and develop two important properties for speech comprehension: phonemic normalization and categorical perception. Recent studies have described diet as an essential factor in normal language development, reporting that breastfed infants show an earlier brain maturity and thus a faster cognitive development. Few studies have described a long-term effect of diet on phonological perception.

Methods

To explore that effect, we compared the event-related potentials (ERPs) collected during an oddball paradigm (frequent /pa/80%, deviant/ba/20%) of infants fed with breast milk (BF), cow-milk-based formula (MF), and soy-based formula (SF), which were assessed at 3, 6, 9, 12, and 24 months of age [Mean across all age groups: 127 BF infants, Mean (M) 39.6 gestation weeks; 121 MF infants, M = 39.16 gestation weeks; 116 SF infants, M = 39.16 gestation weeks].

Results

Behavioral differences between dietary groups in acoustic comprehension were observed at 24-months of age. The BF group displayed greater scores than the MF and SF groups. In phonological discrimination task, the ERPs analyses showed that SF group had an electrophysiological pattern associated with difficulties in phonological-stimulus awareness [mismatch negativity (MMN)-2 latency in frontal left regions of interest (ROI) and longer MMN-2 latency in temporal right ROI] and less brain maturity than BF and MF groups. The SF group displayed more right-lateralized brain recruitment in phonological processing at 12-months old.

Discussion

We conclude that using soy-based formula in a prolonged and frequent manner might trigger a language development different from that observed in the BF or MF groups. The soy-based formula’s composition might affect frontal left-brain area development, which is a nodal brain region in phonological-stimuli awareness.
Characterization of meat quality traits, fatty acids and volatile compounds in Hu and Tan sheep
Authors: Li Jing , Tang Chaohua , Yang Youyou , Hu Ying , Zhao Qingyu , Ma Qing , Yue Xiangpeng , Li Fadi , Zhang Junmin
Published: February 2023

Sheep breed has a major influence on characteristics of meat quality and intramuscular fat (IMF), however, studies into the relationship between sheep breed and meat quality traits rarely consider the large variation in IMF within breed. In this study, groups of 176 Hu and 76 Tan male sheep were established, weaned at 56 days old, with similar weights, and representative samples were selected based on the distribution of IMF in each population, to investigate variations in meat quality, IMF and volatile compound profiles between breeds. Significant differences were observed in drip loss, shear force, cooking loss, and color coordinates between Hu and Tan sheep (p < 0.01). The IMF content and the predominate unsaturated fatty acids, oleic and cis, cis-linoleic acids, were similar. Eighteen out of 53 volatile compounds were identified as important odor contributors. Of these 18 odor-active volatile compounds, no significant concentration differences were detected between breeds. In another 35 volatile compounds, γ-nonalactone was lower in Tan sheep relative to Hu sheep (p < 0.05). In summary, Tan sheep exhibited lower drip loss, higher shear force values, and redder color, had less saturated fatty acids, and contained less γ-nonalactone against Hu sheep. These findings improve understanding of aroma differences between Hu and Tan sheep meat.

Graphical Abstract
Cancer-associated fibroblasts, and clinicopathological characteristics and prognosis of gastric cancer: A systematic review and meta-analysis
Authors: Wei Jinwu , Wang Mingxia , Li Guixiang
Published: February 2023

Objective

To systematically evaluate the relationship between cancer-associated fibroblasts (CAFs) and clinicopathological characteristics and prognosis of gastric cancer, so as to provide new directions and clinical evidence for the diagnosis and treatment of this disease.

Methods

We searched PubMed, Embase, Web of Science, and The Cochrane Library to identify studies on the correlation between tumor-associated fibroblasts and the diagnosis and prognosis of gastric cancer. Two researchers screened the literature independently to extract data, evaluated the quality of the included studies, and used the Review Manager 5.4 software to perform a meta-analysis.

Results

A total of 14 studies involving a total of 2,703 patients were included. The meta-analysis results showed that high expression of CAFs was associated with stage III–IV gastric cancer (relative risk ratio [RR]=1.59; 95% confidence interval [CI]: [1.24–2.04]; P=0.0003), lymph node metastasis (RR=1.51; 95% CI: [1.23–1.87]; P=0.0001), serosal infiltration (RR=1.56, 95% CI: [1.24–1.95]; P=0.0001), diffuse and mixed types in Lauren classification (RR=1.43; 95% CI: [1.18–1.74]; P=0.0003), vascular invasion (RR=1.99; 95% CI: [1.26–3.14]; P=0.003), and overall survival (hazard ratio [HR]=1.38; 95% CI: [1.22–1.56]; P<0.00001). However, the high expression of CAFs was not significantly correlated with poorly differentiated gastric cancer (RR=1.03; 95% CI: [0.96–1.10]; P=0.45) and gastric cancer with tumor diameter >5 cm (RR=1.34; 95% CI: [0.98–1.83]; P=0.07).

Conclusion

The findings of this meta-analysis demonstrated that high expression of CAFs is closely associated with the traditional pathological indicators related to poor prognosis in gastric cancer, and is a valuable prognostic factor in this setting.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358165.
Comparison of 68Ga-FAPI and 18F-FDG PET/CT for the diagnosis of primary and metastatic lesions in abdominal and pelvic malignancies: A systematic review and meta-analysis
Authors: Liu Xue , Liu Huiting , Gao Cailiang , Zeng Wenbing
Published: February 2023

Purpose

The purpose of this study is to compare the application value of 68Ga-FAPI and 18F-FDG PET/CT in primary and metastatic lesions of abdominal and pelvic malignancies (APMs).

Materials

The search, limited to the earliest available date of indexing through 31 July 2022, was performed on PubMed, Embase, and Cochrane Library databases using a data-specific Boolean logic search strategy. We calculated the detection rate (DR) of 68Ga-FAPI and 18F-FDG PET/CT in the primary staging and recurrence of APMs, and pooled sensitivities/specificities based on lymph nodes or distant metastases.

Results

We analyzed 473 patients and 2775 lesions in the 13 studies. The DRs of 68Ga-FAPI and 18F-FDG PET/CT in evaluating the primary staging and recurrence of APMs were 0.98 (95% CI: 0.95-1.00), 0.76 (95% CI: 0.63-0.87), and 0.91(95% CI: 0.61-1.00), 0.56 (95% CI: 0.44-0.68), respectively. The DRs of 68Ga-FAPI and 18F-FDG PET/CT in primary gastric cancer and liver cancer were 0.99 (95% CI: 0.96-1.00), 0.97 (95% CI: 0.89-1.00) and 0.82 (95% CI: 0.59-0.97), 0.80 (95% CI: 0.52-0.98), respectively. The pooled sensitivities of 68Ga-FAPI and 18F-FDG PET/CT in lymph nodes or distant metastases were 0.717(95% CI: 0.698-0.735) and 0.525(95% CI: 0.505-0.546), and the pooled specificities were 0.891 (95% CI: 0.858-0.918) and 0.821(95% CI: 0.786-0.853), respectively.

Conclusions

This meta-analysis concluded that 68Ga-FAPI and 18F-FDG PET/CT had a high overall diagnostic performance in detecting the primary staging and lymph nodes or distant metastases of APMs, but the detection ability of 68Ga-FAPI was significantly higher than that of 18F-FDG. However, the ability of 68Ga-FAPI to diagnose lymph node metastasis is not very satisfactory, and is significantly lower than that of distant metastasis.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022332700.
SARS-CoV-2 infection in children: A 24 months experience with focus on risk factors in a pediatric tertiary care hospital in Milan, Italy
Authors: Di Pietro Giada Maria , Ronzoni Luisa , Meschia Lorenzo Maria , Tagliabue Claudia , Lombardi Angela , Pinzani Raffaella , Bosis Samantha , Marchisio Paola Giovanna , Valenti Luca
Published: February 2023

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is characterized by a wide variety of expressions ranging from asymptomatic to, rarely, critical illness. The basis of this variability is not yet fully understood. The aim of this study was to identify clinical and genetic risk factors predisposing to disease susceptibility and progression in children.

Methods

We enrolled 181 consecutive children aged less than 18 years hospitalized with or for SARS-CoV-2 infection during a period of 24 months. Demographic, clinical, laboratory, and microbiological data were collected. The development of coronavirus disease 2019 (COVID-19)-related complications and their specific therapies were assessed. In a subset of 79 children, a genetic analysis was carried out to evaluate the role of common COVID-19 genetic risk factors (chromosome 3 cluster; ABO-blood group system; FUT2, IFNAR2, OAS1/2/3, and DPP9 loci).

Results

The mean age of hospitalized children was 5.7 years, 30.9% of them being under 1 year of age. The majority of children (63%) were hospitalized for reasons different than COVID-19 and incidentally tested positive for SARS-CoV-2, while 37% were admitted for SARS-CoV-2 infection. Chronic underlying diseases were reported in 29.8% of children. The majority of children were asymptomatic or mildly symptomatic; only 12.7% developed a moderate to critical disease. A concomitant pathogen, mainly respiratory viruses, was isolated in 53.3%. Complications were reported in 7% of children admitted for other reasons and in 28.3% of those hospitalized for COVID-19. The respiratory system was most frequently involved, and the C-reactive protein was the laboratory test most related to the development of critical clinical complications. The main risk factors for complication development were prematurity [relative risk (RR) 3.8, 95% confidence interval (CI) 2.4–6.1], comorbidities (RR 4.5, 95% CI 3.3–5.6), and the presence of coinfections (RR 2.5, 95% CI 1.1–5.75). The OAS1/2/3 risk variant was the main genetic risk factor for pneumonia development [Odds ratio (OR) 3.28, 95% CI 1-10.7; p value 0.049].

Conclusion

Our study confirmed that COVID-19 is generally less severe in children, although complications can develop, especially in those with comorbidities (chronic diseases or prematurity) and coinfections. Variation at the OAS1/2/3 genes cluster is the main genetic risk factor predisposing to COVID-19 pneumonia in children.
Feasibility of high-throughput drug sensitivity screening (HDS)-guided treatment for children with refractory or relapsed acute myeloid leukemia
Authors: Lv Wenxiu , Chen Tianping , Wang Shen , Li Chun , Zhang Bo , Wang Liang , Xv Fang , Cao Fang , Wang Jing , Chen Li , Liao Chenglin , Li Na , Liu Hongjun
Published: February 2023

Relapsed/refractory (rel/ref) acute myeloid leukemia (AML) has a very high mortality rate. At present, hematopoietic stem cell transplantation (HSCT) is the most effective treatment for rel/ref AML. The remission of the primary disease before HSCT is crucial for the transplantation to be effective. Therefore, it is critical to choose a suitable type of chemotherapy before HSCT. Here, we recorded the outcomes of high-throughput drug sensitivity screening (HDS) in children with rel/ref AML. Thirty-seven pediatric rel/ref AML patients who received HDS from September 2017 until July 2021 were analyzed retrospectively. Most of the patients (24 patients, 64.9%) had adverse cytogenetics. Two patients had rel/ref AML with central nervous system leukemia. The complete remission (CR) rate was 67.6%. Eight patients developed IV grade bone marrow suppression. Twenty-three patients (62.2%) underwent HSCT. The 3-year overall survival (OS) and EFS rates were 45.9% and 43.2%, respectively. Infection in the myelosuppression stage was the main cause of death. The outcome of HDS was superior to the commonly reported rates. These results suggest that HDS may be a novel treatment option for pediatric patients with rel/ref AML, and it is a promising transitional regimen prior to HSCT.
Mineral bone disorder in children with chronic kidney disease: Data from the KNOW-Ped CKD (Korean cohort study for outcome in patients with pediatric chronic kidney disease) study
Authors: Jung Jiwon , Lee Keum Hwa , Park Eujin , Park Young Seo , Kang Hee Gyung , Ahn Yo Han , Ha Il-Soo , Kim Seong Heon , Cho Heeyeon , Han Kyoung Hee , Cho Min Hyun , Choi Hyun Jin , Lee Joo Hoon , Shin Jae Il
Published: February 2023

Background

Children with chronic kidney disease (CKD) are at high risk of mineral bone disorder (MBD), which leads to fractures, growth retardation, and cardiovascular disease. We aimed to comprehensively understand the relationship between renal function and factors related to MBD and evaluate the prevalence and distribution characteristics of MBD, specifically among Korean patients from the KNOW-PedCKD cohort.

Methods

From the baseline data of the KNOW-PedCKD cohort, we examined the prevalence and distribution of MBD in 431 Korean pediatric CKD patients, including the level of corrected total calcium, serum phosphate, serum alkaline phosphatase, serum intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF-23), serum vitamin D, fractional excretion of phosphate (FEP), and bone densitometry Z-scores.

Results

The median serum calcium level remained relatively normal regardless of the CKD stage. The levels of 1,25-dihydroxy vitamin D, urine calcium-to-creatinine ratio, and bone densitometry Z-score significantly decreased with advancing CKD stage, while those of serum phosphate, FGF-23, and FEP significantly increased with CKD stage. The prevalence of hyperphosphatemia (17.4%, 23.7%, and 41.2% from CKD stages 3b, 4, and 5, respectively) and hyperparathyroidism (37.3%, 57.4%, 55.3%, and 52.9% from CKD stages 3a, 3b, 4, and 5, respectively) significantly increased with the CKD stage. Prescriptions of medications, such as calcium supplements (39.1%, 42.1%, 82.4%), phosphate binders (39.1%, 43.4%, 82.4%), and active vitamin D (21.7%, 44.7%, and 64.7%) significantly increased with CKD stage 3b, 4, and 5, respectively.

Conclusions

The results demonstrated the prevalence and relationship of abnormal mineral metabolism and bone growth according to CKD stage in Korean pediatric CKD patients for the first time.
Reinforcement learning as an innovative model-based approach: Examples from precision dosing, digital health and computational psychiatry
Authors: Ribba Benjamin
Published: February 2023

Model-based approaches are instrumental for successful drug development and use. Anchored within pharmacological principles, through mathematical modeling they contribute to the quantification of drug response variability and enables precision dosing. Reinforcement learning (RL)—a set of computational methods addressing optimization problems as a continuous learning process—shows relevance for precision dosing with high flexibility for dosing rule adaptation and for coping with high dimensional efficacy and/or safety markers, constituting a relevant approach to take advantage of data from digital health technologies. RL can also support contributions to the successful development of digital health applications, recognized as key players of the future healthcare systems, in particular for reducing the burden of non-communicable diseases to society. RL is also pivotal in computational psychiatry—a way to characterize mental dysfunctions in terms of aberrant brain computations—and represents an innovative modeling approach forpsychiatric indications such as depression or substance abuse disorders for which digital therapeutics are foreseen as promising modalities.
Effect of S-ketamine administered at the end of anesthesia on emergence delirium in preschool children undergoing tonsillectomy and/or adenoidectomy
Authors: Chen Yang , Ru Feixiang , Ye Qiuping , Wu Xinzhe , Hu Xianwen , Zhang Ye , Wu Yun
Published: February 2023

Background: S-ketamine (the S-isomer of ketamine) is twice as potent as the racemic mixture of this agent and carries fewer side effects when administered to humans. Information regarding the use of S-ketamine for the prevention of emergence delirium (ED) is limited. Thus, we evaluated the effect of S-ketamine administered at the end of anesthesia on ED in preschool children undergoing tonsillectomy and/or adenoidectomy.

Methods: We investigated 108 children aged 3–7 years, who were scheduled for elective tonsillectomy and/or adenoidectomy under general anesthesia. They were randomly assigned to receive either S-ketamine 0.2 mg/kg or an equal volume of normal saline at the end of anesthesia. The primary outcome was the highest score on the pediatric anesthesia ED (PAED) scale during the first 30 min post-surgery. The secondary outcomes included the incidence of ED (defined as a score of ≥ 3 on Aono scale), pain score, time to extubation, and incidences of adverse events. Multivariate analyses were also performed using logistic regression to evaluate the independent factors predictive of ED.

Results: The median (interquartile range) PAED score of the S-ketamine group (0 [0, 3]) was significantly lower than that in the control group (1 [0, 7]) (estimate median difference = 0, 95% confidence interval −2 to 0, p = 0.040). Significantly fewer patients in the S-ketamine group had an Aono scale score ≥ 3 (4 [7%] vs. 12 [22%], p = 0.030). Patients in the S-ketamine group also had a lower median pain score than did control subjects (4 [4, 6] vs. 6 [5, 8], p = 0.002). The time to extubation and incidences of adverse events were comparable between the two groups. However, multivariate analyses indicated that except S-ketamine use, pain scores, age and duration of anesthesia were independent factors predictive of ED.

Conclusion: S-ketamine (0.2 mg/kg) administered at the end of anesthesia effectively reduced the incidence and severity of ED in preschool children undergoing tonsillectomy and/or adenoidectomy without prolonging the time to extubation or increasing adverse events. However, S-ketamine use was not an independent factor predictive of ED.
Evaluation of noscapine-licorice combination effects on cough relieving in COVID-19 outpatients: A randomized controlled trial
Authors: Barati Saghar , Feizabadi Faezeh , Khalaj Hakimeh , Sheikhzadeh Hakimeh , Jamaati Hamid R. , Farajidavar Hirad , Dastan Farzaneh
Published: February 2023

Background: As February 2023, SARS-CoV-2 is still infecting people and children worldwide. Cough and dyspnea are annoying symptoms almost present in a large proportion of COVID-19 outpatients, and the duration of these symptoms might be long enough to affect the patients’ quality of life. Studies have shown positive effects for noscapine plus licorice in the previous COVID-19 trials. This study aimed to assess the effects of the combination of noscapine and licorice-for relieving cough in outpatients with COVID-19.

Methods: This randomized controlled trial was conducted on 124 patients at the Dr. Masih Daneshvari Hospital. Participants over 18 years of age with confirmed COVID-19 and cough were allowed to enter the study if the onset of symptoms was less than 5 days. The primary outcome was to assess the response to treatment over 5 days using the visual analogue scale. Secondary outcomes included the assessment of cough severity after 5 days using Cough Symptom Score, as well as the cough-related quality of life and dyspnea relieving. Patients in the noscapine plus licorice group received Noscough® syrup 20 mL every 6 h for 5 days. The control group received diphenhydramine elixir 7 mL every 8 h.

Results: By day five, 53 (85.48%) patients in the Noscough® group and 49 (79.03%) patients in the diphenhydramine group had response to treatment. This difference was not statistically significant (p-value = 0.34). The presence of dyspnea was significantly lower in the Noscough® group versus diphenhydramine at day five (1.61% in the Noscough® group vs. 12.9% in the diphenhydramine group; p-value = 0.03). The cough-related quality of life and severity also significantly favored Noscough® syrup (p-values <0.001).

Conclusion: Noscapine plus licorice syrup was slightly superior to diphenhydramine in relieving cough symptoms and dyspnea in the COVID-19 outpatients. The severity of cough and cough-related quality of life were also significantly better in the noscapine plus licorice syrup. Noscapine plus licorice may be a valuable treatment in relieving cough in COVID-19 outpatients.
Pharmacological effects of methylone and MDMA in humans
Authors: Poyatos Lourdes , Pérez-Mañá Clara , Hladun Olga , Núñez-Montero Melani , de la Rosa Georgina , Martín Soraya , Barriocanal Ana Maria , Carabias Lydia , Kelmendi Benjamin , Taoussi Omayema , Busardò Francesco Paolo , Fonseca Francina , Torrens Marta , Pichini Simona , Farré Magí , Papaseit Esther
Published: February 2023

Methylone is one of the most common synthetic cathinones popularized as a substitute for 3,4-methylenedioxymethamphetamine (MDMA, midomafetamine) owing to its similar effects among users. Both psychostimulants exhibit similar chemistry (i.e., methylone is a β-keto analog of MDMA) and mechanisms of action. Currently, the pharmacology of methylone remains scarcely explored in humans. Herein, we aimed to evaluate the acute pharmacological effects of methylone and its abuse potential in humans when compared with that of MDMA following oral administration under controlled conditions. Seventeen participants of both sexes (14 males, 3 females) with a previous history of psychostimulant use completed a randomized, double-blind, placebo-controlled, crossover clinical trial. Participants received a single oral dose of 200 mg of methylone, 100 mg of MDMA, and a placebo. The variables included physiological effects (blood pressure, heart rate, oral temperature, pupil diameter), subjective effects using visual analog scales (VAS), the short form of the Addiction Research Center Inventory (ARCI), the Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire (VESSPA-SSE), and the Sensitivity to Drug Reinforcement Questionnaire (SDRQ), and psychomotor performance (Maddox wing, psychomotor vigilance task). We observed that methylone could significantly increase blood pressure and heart rate and induce pleasurable effects, such as stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone exhibited an effect profile similar to MDMA, with a faster overall onset and earlier disappearance of subjective effects. These results suggest that abuse potential of methylone is comparable to that of MDMA in humans.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT05488171; Identifier: NCT05488171.
Role of the rhizosphere bacterial community in assisting phytoremediation in a lead-zinc area
Authors: Xiao Yunhua , Chen Liang , Li Chunxiao , Ma Jingjing , Chen Rui , Yang Bo , Liu Gang , Liu Shuming , Fang Jun
Published: February 2023

Heavy metals (HMs) contamination and vegetation destruction in the mining area caused by mining activities are severely increasing. It is urgent to restore vegetation and stabilize HMs. In this study, we compared the ability of HMs phytoextraction/phytostabilization of three dominant plants, including Artemisia argyi (LA), Miscanthus floridulus (LM), and Boehmeria nivea (LZ) in a lead-zinc mining area in Huayuan County (China). We also explored the role of the rhizosphere bacterial community in assisting phytoremediation using 16S rRNA sequencing technology. Bioconcentration factor (BCF) and translocation factor (TF) analysis showed that LA preferred accumulating Cd, LZ preferred accumulating Cr and Sb, and LM preferred accumulating Cr and Ni. Significant (p < 0.05) differences were found among the rhizosphere soil microbial communities of these three plants. The key genera of LA were Truepera and Anderseniella, that of LM were Paracoccus and Erythrobacter, and of LZ was Novosphingobium. Correlation analysis showed some rhizosphere bacterial taxa (e.g., Actinomarinicola, Bacillariophyta and Oscillochloris) affected some soil physicochemical parameters (e.g., organic matter and pH) of the rhizosphere soil and enhanced the TF of metals. Functional prediction analysis of soil bacterial community showed that the relative abundances of genes related to the synthesis of some proteins (e.g., manganese/zinc-transporting P-type ATPase C, nickel transport protein and 1-aminocyclopropane-1-carboxylate deaminase) was positively correlated with the phytoextraction/phytostabilization capacity of plants for heavy metals. This study provided theoretical guidance on selecting appropriate plants for different metal remediation applications. We also found some rhizosphere bacteria might enhance the phytoremediation of multi-metals, which could provide a reference for subsequent research.
Transcriptomic profiling reveals candidate allelopathic genes in rice responsible for interactions with barnyardgrass
Authors: Sultana Most. Humaira , Alamin Md. , Qiu Jie , Fan Longjiang , Ye Chuyu
Published: February 2023

Echinochloa crus-galli (barnyardgrass) is one of the most damaging weeds in rice fields worldwide. Allelopathy has been considered a possible application for weed management. Thus understanding its molecular mechanisms is important for rice production. This study generated transcriptomes from rice under mono- and co-culture with barnyardgrass at two-time points to identify the candidate genes controlling allelopathic interactions between rice and barnyardgrass. A total of 5,684 differentially expressed genes (DEGs) were detected, amongst which 388 genes were transcription factors. These DEGs include genes associated with momilactone and phenolic acid biosynthesis, which play critical roles in allelopathy. Additionally, we found significantly more DEGs at 3 hours than at 3 days, suggesting a quick allelopathic response in rice. Up-regulated DEGs involve diverse biological processes, such as response to stimulus and pathways related to phenylpropanoid and secondary metabolites biosynthesis. Down-regulated DEGs were involved in developmental processes, indicating a balance between growth and stress response to allelopathy from barnyardgrass. Comparison of DEGs between rice and barnyardgrass shows few common genes, suggesting different mechanisms underlying allelopathic interaction in these two species. Our results offer an important basis for identifying of candidate genes responsible for rice and barnyardgrass interactions and contribute valuable resources for revealing its molecular mechanisms.
Predicting heterosis via genetic distance and the number of SNPs in selected segments of chromosomes in maize
Authors: Jiang Fuyan , Yin XingFu , Li Zi Wei , Guo Ruijia , Wang Jing , Fan Jun , Zhang Yudong , Kang Manjit S. , Fan Xingming
Published: February 2023

A reliable method is needed for predicting heterosis to help maize (Zea mays L.) breeders develop new hybrids more efficiently. The objectives of this study were to 1) investigate if the numbers of selected PEUS SNPs (the SNP in the Promoters (1 kb upstream of the start codon), Exons, Untranslated region (UTR), and Stop codons) could be used for predicting MPH or BPH of GY; 2) if the number of PEUS SNPs is a better predictor of MPH and/or BPH of GY than genetic distance (GD). A line × tester experiment was conducted with 19 elite maize inbreds from three heterotic groups, which were crossed with five testers. The multi-location trial data on GY were recorded. Whole-genome resequencing of the 24 inbreds was carried out. After filtration, a total of 58,986,791 SNPs were called with high confidence. Selected SNPs in the promoters, exons, untranslated region (UTRs), and stop codons (PEUS SNPs) were counted, and the GD was calculated. The correlation between heterozygous PEUS SNPs/GD and mean MPH, BPH of GY revealed that 1) both the number of heterozygous PEUS SNP and the GD were highly correlated to both MPH_GY and BPH_GY at p<0.01 with correlation coefficients for the number of heterozygous PEUS SNP being higher than that for GD; 2) the mean number of heterozygous PEUS SNPs was also highly correlated with mean BPH_GY or mean MPH_GY (p<0.05) in the 95 crosses grouped by either male or female parents, implying that inbreds can be selected before making the actual crosses in the field. We concluded that the number of heterozygous PEUS SNPs would be a better predictor of MPH_GY and BPH_GY than GD. Hence, maize breeders could use heterozygous PEUS SNPs to select inbreds with high heterosis potential before actually making the crosses, thus improving the breeding efficiency.
Genome-wide analysis of 14-3-3 gene family in four gramineae and its response to mycorrhizal symbiosis in maize
Authors: Wang Yanping , Xu Qiang , Shan Hanchen , Ni Ying , Xu Minyan , Xu Yunjian , Cheng Beijiu , Li Xiaoyu
Published: February 2023

14-3-3 proteins (regulatory protein family) are phosphate serine-binding proteins. A number of transcription factors and signaling proteins have been shown to bind to the 14-3-3 protein in plants, which plays a role in regulating their growth (seed dormancy, cell elongation and division, vegetative and reproduction growth and stress response (salt stress, drought stress, cold stress). Therefore, the 14-3-3 genes are crucial in controlling how plants respond to stress and develop. However, little is known about the function of 14-3-3 gene families in gramineae. In this study, 49 14-3-3 genes were identified from four gramineae, including maize, rice, sorghum and brachypodium, and their phylogeny, structure, collinearity and expression patterns of these genes were systematically analyzed. Genome synchronization analysis showed large-scale replication events of 14-3-3 genes in these gramineae plants. Moreover, gene expression revealed that the 14-3-3 genes respond to biotic and abiotic stresses differently in different tissues. Upon arbuscular mycorrhizal (AM) symbiosis, the expression level of 14-3-3 genes in maize significantly increased, suggesting the important role of 14-3-3 genes in maize-AM symbiosis. Our results provide a better understanding on the occurrence of 14-3-3 genes in Gramineae plants, and several important candidate genes were found for futher study on AMF symbiotic regulation in maize.
Employing the TAM in predicting the use of online learning during and beyond the COVID-19 pandemic
Authors: Zobeidi Tahereh , Homayoon Seyedeh Bahar , Yazdanpanah Masoud , Komendantova Nadejda , Warner Laura A.
Published: February 2023

Online learning systems have become an applied solution for delivering educational content, especially in developing countries, since the start of the COVID-19 pandemic. The present study is designed to identify the factors influencing the behavioral intention of agricultural students at universities in Iran to use online learning systems in the future. This research uses an extended model in which the constructs of Internet self-efficacy, Internet anxiety, and output quality are integrated into the technology acceptance model (TAM). Data analysis was performed using the SmartPLS technique. The analyses showed the proposed model to be strong in terms of predicting the attitude to online learning and the intention to use it. The extended TAM model fit the data well and predicted 74% of the intention variance. Our findings show attitude and perceived usefulness to have directly affected intention. Output quality and Internet self-efficacy indirectly affected attitude and intention. Research findings can help with the design of educational policies and programs to facilitate education and improve student academic performance.
Worsening psychosis associated with administrations of buspirone and concerns for intranasal administration: A case report
Authors: Apeldoorn Samuel , Chavez Rebecca , Haschemi Freshta , Elsherif Kareem , Weinstein David , Torrico Tyler
Published: February 2023

Buspirone is commonly used to treat generalized anxiety disorder and demonstrates a limited side-effect profile compared to other anxiolytics. Buspirone is considered generally safe, and neuropsychiatric adverse reactions are uncommon. There are rare clinical case reports that suggest buspirone-induced psychosis. We present a case of buspirone worsening psychosis for a patient psychiatrically hospitalized for an episode of decompensated schizoaffective disorder. The patient had a primary diagnosis of schizoaffective disorder and was treated with antipsychotics during this hospitalization, but his symptoms worsened when buspirone was administered on two separate occasions. During the first trial of buspirone, the patient exhibited traits of increased aggression, odd behaviors, and paranoia. The buspirone was discontinued after the patient admitted to hiding his pills to later consume through nasal ingestion. The second trial resulted in repeated exacerbated symptoms of paranoia related to food and substantially decreased oral intake. Considering its complex mechanism of action, buspirone is suggested to derive its neuropharmacological effects through 5-HT1A receptors. However, the drug also has been found to mediate dopamine neurotransmission. Buspirone acts as an antagonist at presynaptic dopamine D2, D3, and D4 receptors. Yet, contrary to expected outcomes, it was unable to produce antipsychotic effects and instead resulted in a substantial increase in dopaminergic metabolites. The route of administration may also play a role in the enhancement of the buspirone’s effects, particularly considering that after first-pass metabolism, buspirone has approximately 4% oral bioavailability. Intranasal administration of buspirone leads to faster drug absorption by direct transport from the nasal mucosa to the brain and increased bioavailability.