bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidural combined optical and electrical stimulation induces high-specificity activation of target muscles in spinal cord injured rats
Authors: Guo Xiao-Jun , Zhao Ziyi , Chang Jia-Qi , He Le-Wei , Su Wen-Nan , Feng Ting , Zhao Can , Xu Meng , Rao Jia-Sheng
Published: November 2023

Introduction

Epidural electrical stimulation (EES) has been shown to improve motor dysfunction after spinal cord injury (SCI) by activating residual locomotor neural networks. However, the stimulation current often spreads excessively, leading to activation of non-target muscles and reducing the accuracy of stimulation regulation.

Objectives

Near-infrared nerve stimulation (nINS) was combined with EES to explore its regulatory effect on lower limb muscle activity in spinal-cord-transected rats.

Methods

In this study, stimulation electrodes were implanted into the rats’ L3–L6 spinal cord segment with T8 cord transected. Firstly, a series of EES parameters (0.2–0.6 mA and 20–60 Hz) were tested to determine those that specifically regulate the tibialis anterior (TA) and medial gastrocnemius (MG). Subsequently, to determine the effect of combined optical and electrical stimulation, near-infrared laser with a wavelength of 808 nm was used to irradiate the L3–L6 spinal cord segment while EES was performed. The amplitude of electromyography (EMG), the specific activation intensity of the target muscle, and the minimum stimulus current intensity to induce joint movement (motor threshold) under a series of optical stimulation parameters (power: 0.0–2.0 W; pulse width: 0–10 ms) were investigated and analyzed.

Results

EES stimulation with 40 Hz at the L3 and L6 spinal cord segments specifically activated TA and MG, respectively. High stimulation intensity (>2 × motor threshold) activated non-target muscles, while low stimulation frequency (<20 Hz) produced intermittent contraction. Compared to electrical stimulation alone (0.577 ± 0.081 mV), the combined stimulation strategy could induce stronger EMG amplitude of MG (1.426 ± 0.365 mV) after spinal cord injury (p < 0.01). The combined application of nINS effectively decreased the EES-induced motor threshold of MG (from 0.237 ± 0.001 mA to 0.166 ± 0.028 mA, p < 0.001). Additionally, the pulse width (PW) of nINS had a slight impact on the regulation of muscle activity. The EMG amplitude of MG only increased by ~70% (from 3.978 ± 0.240 mV to 6.753 ± 0.263 mV) when the PW increased by 10-fold (from 1 to 10 ms).

Conclusion

The study demonstrates the feasibility of epidural combined electrical and optical stimulation for highly specific regulation of muscle activity after SCI, and provides a new strategy for improving motor dysfunction caused by SCI.
Loss of ASD-related molecule Cntnap2 affects colonic motility in mice
Authors: Robinson Beatriz G. , Oster Beau A. , Robertson Keiramarie , Kaltschmidt Julia A.
Published: November 2023

Gastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Cntnap2) is an ASD-related synaptic cell-adhesion molecule important for sensory processing. In this study, we examine the role of Cntnap2 in GI motility by characterizing Cntnap2’s expression in the ENS and assessing GI function in Cntnap2 mutant mice. We find Cntnap2 expression predominately in enteric sensory neurons. We further assess in vivo and ex vivo GI motility in Cntnap2 mutants and show altered transit time and colonic motility patterns. The overall organization of the ENS appears undisturbed. Our results suggest that Cntnap2 plays a role in GI function and may provide a molecular link between ASD and GI dysfunction.
Effect of high hydrostatic pressure on aroma volatile compounds and aroma precursors of Hami melon juice
Authors: Pei Longying , Liu Wei , Jiang Luxi , Xu Heng , Liu Luping , Wang Xiaoyu , Liu Manli , Abudureheman Buhailiqiemu , Zhang Heng , Chen Jiluan
Published: November 2023

High hydrostatic pressure (HHP) treatment is an effective technique for processing heat-sensitive fruits and causes changes in volatile compounds and their precursors while maintaining quality. We investigated the changes and correlations of volatile compounds, related enzyme activities and precursor amino acids, and fatty acids in Hami melon juice under 350–500 MPa pressure. The application of HHP treatment resulted in a considerable reduction of esters and a substantial increase in aldehydes and alcohols in C6 and C9. Activities of lipoxygenase (LOX), alcohol acyltransferase (AAT), and phospholipase A2 (PLA2) were lower than those of the untreated group, alcohol dehydrogenase (ADH) activity was reversed. When compared to fresh cantaloupe juice, there was an increase in both the types and contents of amino acids with lower total fatty acid contents than the control group. Positive correlations were observed among six ester-related substances and eight alcohol-related substances. Additionally, the correlations between volatile compounds and fatty acids were more substantial compared to those between volatile compounds and amino acids. HHP treatment increases Hami melon flavor precursors and is an effective way to maintain the aroma volatile compounds and flavor of Hami melon juice.
Why we should care about gas pockets in online adaptive MRgRT: a dosimetric evaluation
Authors: Nardini Matteo , Meffe Guenda , Galetto Matteo , Boldrini Luca , Chiloiro Giuditta , Romano Angela , Panza Giulia , Bevacqua Andrea , Turco Gabriele , Votta Claudio , Capotosti Amedeo , Moretti Roberto , Gambacorta Maria Antonietta , Indovina Luca , Placidi Lorenzo
Published: November 2023

Introduction

Contouring of gas pockets is a time consuming step in the workflow of adaptive radiotherapy. We would like to better understand which gas pockets electronic densitiy should be used and the dosimetric impact on adaptive MRgRT treatment.

Materials and methods

21 CT scans of patients undergoing SBRT were retrospectively evaluated. Anatomical structures were contoured: Gross Tumour Volume (GTV), stomach (ST), small bowel (SB), large bowel (LB), gas pockets (GAS) and gas in each organ respectively STG, SBG, LBG. Average HU in GAS was converted in RED, the obtained value has been named as Gastrointestinal Gas RED (GIGED). Differences of average HU in GAS, STG, SBG and LBG were computed. Three treatment plans were calculated editing the GAS volume RED that was overwritten with: air RED (0.0012), water RED (1.000), GIGED, generating respectively APLAN, WPLAN and the GPLAN. 2-D dose distributions were analyzed by gamma analysis. Parameter called active gas volume (AGV) was calculated as the intersection of GAS with the isodose of 5% of prescription dose.

Results

Average HU value contained in GAS results to be equal to -620. No significative difference was noted between the average HU of gas in different organ at risk. Value of Gamma Passing Rate (GPR) anticorrelates with the AGV for each plan comparison and the threshold value for GPR to fall below 90% is 41, 60 and 139 cc for WPLANvsAPLAN, GPLANvsAPLAN and WPLANvsGPLAN respectively.

Discussions

GIGED is the right RED for Gastrointestinal Gas. Novel AGV is a useful parameter to evaluate the effect of gas pocket on dose distribution.
Revolutionizing orofacial pain management: the promising potential of stem cell therapy
Authors: Ren Ke , Vickers Russel , Murillo Josue , Ruparel Nikita B.
Published: November 2023

Orofacial pain remains a significant health issue in the United States. Pain originating from the orofacial region can be composed of a complex array of unique target tissue that contributes to the varying success of pain management. Long-term use of analgesic drugs includes adverse effects such as physical dependence, gastrointestinal bleeding, and incomplete efficacy. The use of mesenchymal stem cells for their pain relieving properties has garnered increased attention. In addition to the preclinical and clinical results showing stem cell analgesia in non-orofacial pain, studies have also shown promising results for orofacial pain treatment. Here we discuss the outcomes of mesenchymal stem cell treatment for pain and compare the properties of stem cells from different tissues of origin. We also discuss the mechanism underlying these analgesic/anti-nociceptive properties, including the role of immune cells and the endogenous opioid system. Lastly, advancements in the methods and procedures to treat patients experiencing orofacial pain with mesenchymal stem cells are also discussed.
Evaluation of febrile seizures in children infected with SARS-CoV-2 Omicron variant in Yunnan, China: a multi-center, retrospective observational study
Authors: Liu Hai-feng , Lu Rui , Yang Jian , Xiang Mei , Ban Deng , Yang Jia-wu , Guo Zheng-hong , Yuan Ting-yun , Fu Hong-min
Published: November 2023

Background

The SARS-CoV-2 Omicron variant was reported to be linked to febrile seizures (FSs), but studies on FSs in children with Omicron infection remain relatively scarce, especially in the Chinese population. This study aimed to investigate the characteristics of children diagnosed with Omicron infection with FSs in Yunnan, China, and evaluate the potential association between FSs and Omicron infection.

Methods

This study was conducted at four hospitals in Yunnan from December 8, 2022, to January 8, 2023, and consisted of 590 pediatric subjects. According to clinical characteristics, 85, 129 and 376 subjects were divided into the FS-only, Omicron-FS, and Omicron-only groups, respectively. Demographic, clinical and laboratory data were retrospectively collected for analysis.

Results

The incidence of FSs in children with Omicron infection was 25.5% (129/505). Older age, stronger male predominance, as well as lower proportions of prior history and family history of seizures were observed in Omicron-FS and Omicron-only groups than in FS-only group, but there were no differences in these four above-mentioned events between these two Omicron-related groups. Compared to FS-only group, Omicron-FS group also had a shorter fever-to-seizure onset duration and more frequent seizures during a single course of fever. Moreover, higher levels of IL-6, TNF-α and ferritin as well as decreased counts of leukocytes and lymphocytes were confirmed in Omicron-FS group than in FS-only and Omicron-only groups. Regarding COVID-19 vaccination status, Omicron-FS group revealed a higher proportion of unvaccinated children and a lower proportion of three-dose vaccination than Omicron-only group. As for clinical outcomes, proportions of mechanical ventilation and intensive care unit admission observed in the two Omicron-related groups were notably higher than those in FS-only group. Meanwhile, Omicron-FS group showed the longest length of hospital stay, followed by Omicron-only group and FS-only group, in order. Finally, all patients but one who died of fulminant myocarditis had been successfully discharged.

Conclusions

The incidence of FSs in children with Omicron infection was 25.5% in Yunnan. FSs might be a clinical sign deserving more attention in children with Omicron infection. Furthermore, COVID-19 vaccination is likely to provide effective protection against Omicron-related FSs in children.
Streptococcus pneumoniae associated hemolytic uremic syndrome in children
Authors: Young Heather L. , Brown Clare C. , Crawford Brendan , Blaszak Richard T. , Prodhan Parthak
Published: November 2023

Introduction

Previous small-scale, single-center investigations of Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) have shown increased disease severity among SpHUS relative to non-SpHUS patients. Our study compares the impact of S. pneumoniae on patient outcomes between SpHUS cases and non-SpHUS controls using the national, multicenter retrospective Pediatric Health Information Systems (PHIS) Database.

Methods

Children <18 years of age with a diagnosis of HUS were included. Univariate analyses and multivariable linear and logistic regressions were utilized to assess the impact of S. pneumoniae on mortality, length of stay (LOS), intensive care unit admission (ICU), and mechanical ventilation use. Models were adjusted for demographic and clinical characteristics, including cardiac, neurologic, pulmonary, gastrointestinal, immunologic and renal clinical complications.

Results

Of 3,952 index HUS hospitalizations, 231 (5.8%) were due to SpHUS. SpHUS patients had worse outcomes, including longer hospital stays, increased rate of ICU admission, and increased use of mechanical ventilation (p < 0.001 for all). There was a strong positive relationship between clinical complications and adverse outcomes. After adjusting for covariates, SpHUS was associated with an increase in hospital LOS by 3.47 days (p = 0.009) and overall ICU-LOS by 4.21 days (p < 0.001). SpHUS was also associated with increased likelihood of mechanical ventilation (OR: 3.08; p < 0.001), with no increase in ICU admission (p = 0.070) and in-hospital mortality (p = 0.3874).

Discussion

Our study highlights that SpHUS patients are at increased risk of multiple adverse outcomes likely due to the summative impact of pneumococcal infection and HUS as well as more frequent clinical complications.
A Y-shape connection device for pediatric patients with an indwelling catheter (Dia = 8Fr) during urodynamic studies, especially for filling phase measurements: a single-center prospective study for safety and effectiveness
Authors: Yang Shi-Qin , Zeng Xiao , Peng Liao , Shen Si-Hong , Zhang Jie , Huang Zhi-Hui , Shen Hong , Luo De-yi , Jin Tao
Published: November 2023

Introduction

This prospective study aimed to assess the effectiveness of a Y-shape connection device in reducing pain and bleeding in pediatric patients with indwelling catheters during urodynamic studies (UDS), while also obtaining effective results in the filling phase.

Methods

A total of 45 pediatric patients with a mean age of 13 years were included, all of whom underwent both a UDS with the Y-shape connection device (Method A) and a standard UDS procedure (Method B).

Results

The Y-shape connection device demonstrated similar overall urodynamic parameters compared to the standard procedure, while also resulting in significantly less bleeding (P = 0.006) and lower VAS scores during (1.12 ± 0.58 vs. 3.88 ± 1.01, P = 0.001) and after (0.12 ± 0.08 vs 2.91 ± 0.89, P = 0.001) the procedure. No adverse events were reported at the 1-month follow-up.

Discussion

These findings suggest that the Y-shape connection device can effectively reduce pain and bleeding during and after UDS in pediatric patients with indwelling catheters (Dia = 8Fr), while also obtaining effective results in the filling phase. Therefore, this Y-shape connection device has a more significant value for children who require urodynamic studies and place more emphasis on filling phase parameters.

Clinical trial registration

ChiCTR2300068280.
Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers
Authors: Sorić Hosman Iva , Cvitković Roić Andrea , Fištrek Prlić Margareta , Vuković Brinar Ivana , Lamot Lovro
Published: November 2023

Autosomal dominant polycystic kidney disease (ADPKD) is one of the leading causes of end-stage renal disease. In spite of the recent tremendous progress in the understanding of ADPKD pathogenesis, the molecular mechanisms of the disease remain incompletely understood. Considering emerging new targeted therapies for ADPKD, it has become crucial to disclose easily measurable and widely available biomarkers for identifying patients with future rapid disease progression. This review encompasses all the research with a shared goal of identifying promising serum or urine biomarkers for predicting ADPKD progression or response to therapy. The rate of the ADPKD progress varies significantly between patients. The phenotypic variability is only partly explained by the underlying genetic lesion diversity. Considering significant decline in kidney function in ADPKD is not usually evident until at least 50% of the parenchyma has been destroyed, conventional kidney function measures, such as glomerular filtration rate (GFR), are not suitable for monitoring disease progression in ADPKD, particularly in its early stages. Since polycystic kidney enlargement usually precedes the decline in GFR, height-adjusted total kidney volume (ht-TKV) has been accepted as an early biomarker for assessing disease severity in ADPKD patients. However, since measuring ht-TKV is time-consuming and observer-dependent, the identification of a sensitive and quickly measurable biomarker is of a great interest for everyday clinical practice. Throughout the last decade, due to development of proteomic and metabolomic techniques and the enlightenment of multiple molecular pathways involved in the ADPKD pathogenesis, a number of urine and serum protein biomarkers have been investigated in ADPKD patients, some of which seem worth of further exploring. These include copeptin, angiotensinogen, monocyte chemoattractant protein 1, kidney injury molecule-1 and urine-to-plasma urea ratio among many others. The aim of the current review is to provide an overview of all of the published evidence on potentially clinically valuable serum and urine biomarkers that could be used for predicting disease progression or response to therapy in patients with ADPKD. Hopefully, this review will encourage future longitudinal prospective clinical studies evaluating proposed biomarkers as prognostic tools to improve management and outcome of ADPKD patients in everyday clinical practice.
The alleviating effect of Scutellaria amoena extract on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NLRP3/ASC/caspase-1 axis
Authors: Lin Yu-Ping , Fang Qiong-Lian , Fu Sheng-Nan , Li Xin-Ping , Shi Rui , Du Cheng-Hong , Qiao Xue , Yin Xun-Qing , Zeng Yong-Cheng , Zhao Xiu-Juan , Hua Yan
Published: November 2023

Background:Scutellaria amoena (SA) is the root of S. amoena C.H. Wright of Labiatae, also known as Scutellaria southwestern. This is mainly distributed in Sichuan, Yunnan, and Guizhou in China. In southwest China, SA is used as an alternative method to genuine medicine for the treatment of allergy, diarrhea, inflammation, hepatitis, and bronchitis. Thus far, studies on the effects of SA on non-alcoholic steatohepatitis (NASH) are lacking. This paper investigated the effect of SA on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NOD-like receptor 3 (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis.

Methods: A NASH rat model was induced by a high-fat diet (HFD) for 12 weeks, and rats were orally given different doses of SA extracts (150 and 300 mg/kg/d) for 6 weeks. Changes in histological parameters, body weight, organ indexes, cytokines, and biochemical parameters related to NLRP3 in NASH rats were checked. 16S rRNA gene sequencing and UPLC-MS/MS technology were used to analyze the changes in the gut microbiota composition and its metabolites in NASH rats.

Results: SA significantly inhibited the HFD-induced increase in body weight, lipid levels, and inflammatory infiltration. SA notably inhibited the HFD-induced increase in the upper and lower factors of NLRP3, such as transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, pro-IL-18, IL-1β, pro-IL-1β, NLRP3, ASC, and caspase-1. Additionally, mRNA expressions of caspase-1, NLRP3, and ASC were significantly downregulated after SA treatment. The results of the intestinal flora showed that SA could increase the diversity of flora and change its structure and composition in NASH rats by reducing Firmicutes/Bacteroidetes (F/B) ratio, Blautia (genus), Lachospiraceae (family), and Christensenellaceae R-7 group (genus), and increasing Muribaculaceae (family) and Bacteroides (genus). The metabolomics revealed that 24 metabolites were possibly the key metabolites for SA to regulate the metabolic balance of NASH rats, including chenodeoxycholic acid, xanthine, and 9-OxoODE. Nine metabolic pathways were identified, including primary bile acid biosynthesis, bile secretion, purine metabolism, and secondary bile acid biosynthesis.

Conclusion: SA can regulate the intestinal microbial balance and metabolic disorder by inhibiting the NLRP3/ASC/caspase-1 axis to relieve NASH.
The effect of ginger extract on cisplatin-induced acute anorexia in rats
Authors: Kim Hyeonah , Park Keun-Tae , Jo Heejoon , Shin Yuchan , Chung Geehoon , Ko Seong-Gyu , Jin Young-Ho , Kim Woojin
Published: November 2023

Cisplatin is a platinum-based chemotherapeutic agent widely used to treat various cancers. However, several side effects have been reported in treated patients. Among these, acute anorexia is one of the most severe secondary effects. In this study, a single oral administration of 100 or 500 mg/kg ginger extract (GE) significantly alleviated the cisplatin-induced decrease in food intake in rats. However, these body weight and water intake decreases were reversed in the 100 mg/kg group rats. To elucidate the underlying mechanism of action, serotonin (5-HT) and 5-HT2C, 3A, and 4 receptors in the nodose ganglion of the vagus nerve were investigated. The results showed that cisplatin-induced increases in serotonin levels in both the blood and nodose ganglion tissues were significantly decreased by100 and 500 mg/kg of GE administration. On 5-HT receptors, 5-HT3A and 4, but not 2C receptors, were affected by cisplatin, and GE 100 and 500 mg/kg succeeded in downregulating the evoked upregulated gene of these receptors. Protein expression of 5-HT3A and 4 receptors were also reduced in the 100 mg/kg group. Furthermore, the injection of 5-HT3A, and 4 receptors antagonists (palonostron, 0.1 mg/kg, i.p.; piboserod, 1 mg/kg, i.p., respectively) in cisplatin treated rats prevented the decrease in food intake. Using high-performance liquid chromatography (HPLC) analysis, [6]-gingerol and [6]-shogaol were identified and quantified as the major components of GE, comprising 4.12% and 2.15% of the GE, respectively. Although [6]-gingerol or [6]-shogaol alone failed to alleviate the evoked anorexia, when treated together, the effect was significant on the cisplatin-induced decrease in food intake. These results show that GE can be considered a treatment option to alleviate cisplatin-induced anorexia.
The influence of general practitioner and patient sex on the treatment of major depression
Authors: Jufresa-Blanch Elisabeth , Carrilero Neus , García-Altés Anna
Published: November 2023

Introduction: Biological and sociocultural factors may lead to a significant gender bias in the treatment of major depression and thus contribute to accentuating gender inequalities. However, the influence of the general practitioner’s (GP’s) sex on the prescription of antidepressants has not been adequately assessed in previous work and remains unclear. This retrospective cohort study aims to determine the influence of GP and patient sex on the treatment of major depression.

Methods: The study population comprised 87,629 patients (33.56% male patients and 66.44% female patients) aged over 15 years newly diagnosed with major depression recorded between 2017 and 2019 in Catalonia, Spain. Logistic regression models were used to evaluate the effect of GP sex on the therapeutic strategy (i.e., whether antidepressants were prescribed at the first diagnostic visit). Cox proportional hazards models and survival analyses were conducted to compare, according to GP and patient sex, the probability that a patient would be prescribed an antidepressant at any time during the study period. Finally, a multiple linear regression analysis was performed to assess the pharmacological intensity of the treatment [monthly fluoxetine-equivalent defined daily dose (DDD)].

Results: Female patients were more likely to be prescribed an antidepressant at the time of diagnosis, both by male [OR = 1.11, 95% CI = (1.05, 1.17), p<0.001] and female GPs [OR = 1.13, 95% CI = (1.09, 1.17), p<0.001]. Similarly, female patients were 8% and 9% more likely than male patients to be prescribed an antidepressant from male [HR = 1.08, 95% CI = (1.05, 1.11), p<0.001] and female GPs [HR = 1.09, 95% CI = (0.92, 1.07), p<0.001], respectively, during the study period. Female GPs prescribed less antidepressants than male GPs: an average of 0.39 less monthly fluoxetine-equivalent DDD [β = −0.39, 95% CI = (0.10, −3.92), p<0.001].

Discussion: Few differences are observed between male and female GPs regarding the therapeutic strategy and its intensity for the treatment of major depression. However, both male and female GPs are influenced by biases and stereotypes that entail differential antidepressant-prescribing behaviors in accordance with the sex of the patient and their characteristics.
Structure-function and rational design of a spider toxin Ssp1a at human voltage-gated sodium channel subtypes
Authors: Dongol Yashad , Wilson David T. , Daly Norelle L. , Cardoso Fernanda C. , Lewis Richard J.
Published: November 2023

The structure-function and optimization studies of NaV-inhibiting spider toxins have focused on developing selective inhibitors for peripheral pain-sensing NaV1.7. With several NaV subtypes emerging as potential therapeutic targets, structure-function analysis of NaV-inhibiting spider toxins at such subtypes is warranted. Using the recently discovered spider toxin Ssp1a, this study extends the structure-function relationships of NaV-inhibiting spider toxins beyond NaV1.7 to include the epilepsy target NaV1.2 and the pain target NaV1.3. Based on these results and docking studies, we designed analogues for improved potency and/or subtype-selectivity, with S7R-E18K-rSsp1a and N14D-P27R-rSsp1a identified as promising leads. S7R-E18K-rSsp1a increased the rSsp1a potency at these three NaV subtypes, especially at NaV1.3 (∼10-fold), while N14D-P27R-rSsp1a enhanced NaV1.2/1.7 selectivity over NaV1.3. This study highlights the challenge of developing subtype-selective spider toxin inhibitors across multiple NaV subtypes that might offer a more effective therapeutic approach. The findings of this study provide a basis for further rational design of Ssp1a and related NaSpTx1 homologs targeting NaV1.2, NaV1.3 and/or NaV1.7 as research tools and therapeutic leads.
NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor
Authors: Zhang Meng , Zhang Zhenyong , Tian Xin , Zhang Enchong , Wang Yichun , Tang Jun , Zhao Jianzhu
Published: November 2023

Tumorigenesis and tumor development are closely related to the abnormal regulation of ubiquitination. Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), an E3 ubiquitin ligase critical to the ubiquitination process, plays key roles in the regulation of cancer stem cells, as well as tumor cell functions, including cell proliferation, apoptosis, cell cycle regulation, migration, invasion, epithelial–mesenchymal transition (EMT), and tumor drug resistance, by controlling subsequent protein degradation through ubiquitination. NEDD4L primarily functions as a tumor suppressor in several tumors but also plays an oncogenic role in certain tumors. In this review, we comprehensively summarize the relevant signaling pathways of NEDD4L in tumors, the regulatory mechanisms of its upstream regulatory molecules and downstream substrates, and the resulting functional alterations. Overall, therapeutic strategies targeting NEDD4L to treat cancer may be feasible.
Harmonising knowledge for safer materials via the “NanoCommons” Knowledge Base
Authors: Maier Dieter , Exner Thomas E. , Papadiamantis Anastasios G. , Ammar Ammar , Tsoumanis Andreas , Doganis Philip , Rouse Ian , Slater Luke T. , Gkoutos Georgios V. , Jeliazkova Nina , Ilgenfritz Hilmar , Ziegler Martin , Gerhard Beatrix , Kopetsky Sebastian , Joshi Deven , Walker Lee , Svendsen Claus , Sarimveis Haralambos , Lobaskin Vladimir , Himly Martin , van Rijn Jeaphianne , Winckers Laurent , Millán Acosta Javier , Willighagen Egon , Melagraki Georgia , Afantitis Antreas , Lynch Iseult
Published: November 2023

In mediaeval Europe, the term “commons” described the way that communities managed land that was held “in common” and provided a clear set of rules for how this “common land” was used and developed by, and for, the community. Similarly, as we move towards an increasingly knowledge-based society where data is the new oil, new approaches to sharing and jointly owning publicly funded research data are needed to maximise its added value. Such common management approaches will extend the data’s useful life and facilitate its reuse for a range of additional purposes, from modelling, to meta-analysis to regulatory risk assessment as examples relevant to nanosafety data. This “commons” approach to nanosafety data and nanoinformatics infrastructure provision, co-development, and maintenance is at the heart of the “NanoCommons” project and underpins its post-funding transition to providing a basis on which other initiatives and projects can build. The present paper summarises part of the NanoCommons infrastructure called the NanoCommons Knowledge Base. It provides interoperability for nanosafety data sources and tools, on both semantic and technical levels. The NanoCommons Knowledge Base connects knowledge and provides both programmatic (via an Application Programming Interface) and a user-friendly graphical interface to enable (and democratise) access to state of the art tools for nanomaterials safety prediction, NMs design for safety and sustainability, and NMs risk assessment, as well. In addition, the standards and interfaces for interoperability, e.g., file templates to contribute data to the NanoCommons, are described, and a snapshot of the range and breadth of nanoinformatics tools and models that have already been integrated are presented Finally, we demonstrate how the NanoCommons Knowledge Base can support users in the FAIRification of their experimental workflows and how the NanoCommons Knowledge Base itself has progressed towards richer compliance with the FAIR principles.
Numerical study of second-grade fuzzy hybrid nanofluid flow over the exponentially permeable stretching/shrinking surface
Authors: Zulqarnain Rana Muhammad , Nadeem Muhammad , Siddique Imran , Samar Mahvish , Khan Ilyas , Mohamed Abdullah
Published: November 2023

The study of hybrid nanoliquids can aid in developing numerous advanced features that facilitate heat transmission, such as pharmaceutical processes, hybrid-powered engines, microelectronics, engine cooling, and domestic refrigerators. In the current study, a mathematical model is designed to elaborate the physical inception of an unsteady second-grade hybrid nanofluid with Al2O3−Cu/SA, a combination concentrated over the permeable exponentially heated stretching/shrinking sheet under hydromagnetic, heat source/sink, and viscous dissipation implications. The set of similarity transforms is used to convert underlying partial differential equations into the system of ordinary differential equations. The well-known homotopy analysis method is applied to tackle the formulated differential system in the MATHEMATICA program, which can obtain non-uniqueness outcomes. The imprecision of nanofluid and hybrid nanofluid volume fractions was modeled as a triangular fuzzy number [0%, 5%, 10%] for comparison. The double parametric approach was applied to deal with the fuzziness of the associated fuzzy parameters. The nonlinear ordinary differential equations are converted into fuzzy differential equations, and the homotopy analysis method is used for the fuzzy solution. In terms of code validity, our results are matched to previous findings. The features of several parameters against the velocity, surface-friction coefficient, heat transfer, and Nusselt number are described via graphs. Furthermore, the nanoparticle volume fraction magnifies the fluid temperature and retards the flow profile throughout the domain, according to our findings. Thermal profiles increase with progress in the heat source, nanoparticles volumetric fractions, viscous dissipation, and nonlinear thermal radiation. The percentage increase in the drag force and heat transfer rate are 15.18 and 5.54 when the magnetic parameter takes input in the range 0.1 ≤ M ≤ 0.3 and nanoparticle volume fraction inputs 0.01 ≤ ϕ1 ≤ 0.15. From our observation, the hybrid nanofluid displays the maximum heat transfer compared to nanofluids. This important contribution will support industrial growth, particularly in the processing and manufacturing sectors.
Toxicological effects of copper on bioaccumulation and mRNA expression of antioxidant, immune, and apoptosis-related genes in Chinese striped-necked turtle (Mauremys sinensis)
Authors: Ali Zeeshan , Khan Ijaz , Iqbal Muhammad Shahid , Zhang Qiongyu , Ai Xiaoqi , Shi Haitao , Ding Li , Hong Meiling
Published: November 2023

Heavy metals are among the most ubiquitous environmental pollutants of recent decades. Copper is commonly used to control algal blooms or macrophyte and waste infestations, its ambient concentration has increased significantly, indicating possible environmental risk. To investigate the effects of copper exposure on bioaccumulation, antioxidant defense, immune response, and apoptosis in the Chinese Striped-necked Turtle Mauremys sinensis, three experimental groups, control (0.0 mg/L), Cu2 (2 mg/L) and Cu4 (4 mg/L) were designed, and sampled at 14 and 28 days. Results showed that copper accumulates in different organs depending on the concentration and exposure time, Liver > Kidney > Gut > Heart > Brain > Muscle and the time order was 28 days > 14 days. The liver enzymes AST, ALT, and ALP decreased when the turtles were exposed to copper stress, while the contents of bilirubin TBIL, DBIL, IBIL, and LDH showed a significant upward trend. Similarly, the mRNA expression level of acetylcholinesterase AChE in the brain was significantly downregulated upon copper exposure. An upward trend was noticed in the liver Metallothionein MT mRNA expression levels compared to the control group. The mRNA expression levels of antioxidant enzymes CAT, SOD, MnSOD, and GSH-PX1 in the liver increased initially and then significantly decreased. Furthermore, the relative mRNA expression levels of inflammatory cytokines IL-1β, IL-8, TNF-α, and IFN-γ involved in inflammatory response significantly upregulated. Copper significantly increased the hepatic mRNA transcription of heat shock proteins HSP70 and HSP90 at different exposure durations. In addition, the relative mRNA levels of caspase3, caspase8, and caspase9 related to the caspase-dependent apoptotic pathway significantly increased under copper stress. These results explain that copper toxicity causes bioaccumulation, promotes oxidative stress, obstructs immunity, and induces inflammation and apoptosis by altering their gene expression levels in M. sinensis.
Trust in the police and affective evaluation of police faces: a preliminary study
Authors: Brunet Nicolas M. , Marsh Natalya K. , Bean Caitlin R. , Powell Zachary A.
Published: November 2023

Introduction

A study was conducted to investigate if an individual’s trust in law enforcement affects their perception of the emotional facial expressions displayed by police officers.

Methods

The study invited 77 participants to rate the valence of 360 face images. Images featured individuals without headgear (condition 1), or with a baseball cap (condition 2) or police hat (condition 3) digitally added to the original photograph. The images were balanced across sex, race/ethnicity (Asian, African American, Latine, and Caucasian), and facial expression (Happy, Neutral, and Angry). After rating the facial expressions, respondents completed a survey about their attitudes toward the police.

Results

The results showed that, on average, valence ratings for “Angry” faces were similar across all experimental conditions. However, a closer examination revealed that faces with police hats were perceived as angrier compared to the control conditions (those with no hat and those with a baseball cap) by individuals who held negative views of the police. Conversely, participants with positive attitudes toward the police perceived faces with police hats as less angry compared to the control condition. This correlation was highly significant for angry faces (p < 0.01), and stronger in response to male faces compared to female faces but was not significant for neutral or happy faces.

Discussion

The study emphasizes the substantial role of attitudes in shaping social perception, particularly within the context of law enforcement.
Identifying the effects of scaffolding on learners’ temporal deployment of self-regulated learning operations during game-based learning using multimodal data
Authors: Dever Daryn A. , Wiedbusch Megan D. , Romero Sarah M. , Smith Kevin , Patel Milouni , Sonnenfeld Nathan , Lester James , Azevedo Roger
Published: November 2023

Introduction

Self-regulated learning (SRL), or learners’ ability to monitor and change their own cognitive, affective, metacognitive, and motivational processes, encompasses several operations that should be deployed during learning including Searching, Monitoring, Assembling, Rehearsing, and Translating (SMART). Scaffolds are needed within GBLEs to both increase learning outcomes and promote the accurate and efficient use of SRL SMART operations. This study aims to examine how restricted agency (i.e., control over one’s actions) can be used to scaffold learners’ SMART operations as they learn about microbiology with Crystal Island, a game-based learning environment.

Methods

Undergraduate students (N = 94) were randomly assigned to one of two conditions: (1) Full Agency, where participants were able to make their own decisions about which actions they could take; and (2) Partial Agency, where participants were required to follow a pre-defined path that dictated the order in which buildings were visited, restricting one’s control. As participants played Crystal Island, participants’ multimodal data (i.e., log files, eye tracking) were collected to identify instances where participants deployed SMART operations.

Results

Results from this study support restricted agency as a successful scaffold of both learning outcomes and SRL SMART operations, where learners who were scaffolded demonstrated more efficient and accurate use of SMART operations.

Discussion

This study provides implications for future scaffolds to better support SRL SMART operations during learning and discussions for future directions for future studies scaffolding SRL during game-based learning.
A descriptive analysis of children seeking medical attention for problematic sexualized behavior
Authors: Thompson Kara , Svendsen Sasha
Published: November 2023

Introduction

Problematic Sexualized Behavior (PSB) in children is an increasingly prevalent and often misunderstood issue that impacts the well-being of children. Quantifying the numbers of affected children is challenging due to inconsistencies in how these children are identified, as well as misperceptions surrounding the issue and lack of a coordinated community response.

Methods

In this single-center retrospective case review, we attempt to report data on child demographics and case characteristics for children presenting to one Child Protection Program (CPP) medical specialty team for concern of PSB.

Results

A total of 224 children were identified as having engaged in PSB during the study period. 110 (49%) of these children were referred to the CPP for medical evaluation and medically triaged by the team. The remaining 114 children (51%) were identified through the medical triage of the presenting cases as having engaged in PSB with the index children, but were not referred to CPP for medical care themselves. The majority of children who were referred (69%) were the recipient of the PSB, compared to being the displayer of the behavior (20%). Of the recipient cases, the child displaying PSB was also referred to the CPP only 14.5% of the time.

Discussion

These results highlight that the number of children presenting for medical evaluation with concern of PSB is a significant underestimation of the prevalence of PSB in the community. This notable gap in identification of children engaging in PSB prevents service delivery for these children, including medical evaluation. The results also demonstrate that children displaying PSB were disproportionately missing from care and represent a specific area of missed opportunity for intervention and support by medical professionals.
The effectiveness, efficiency, and acceptability of EMDR vs. EMDR 2.0 vs. the Flash technique in the treatment of patients with PTSD: study protocol for the ENHANCE randomized controlled trial
Authors: Alting van Geusau Valentijn V. P. , de Jongh Ad , Nuijs Mae D. , Brouwers Thomas C. , Moerbeek Mirjam , Matthijssen Suzy J. M. A.
Published: November 2023

Background

Several widely studied therapies have proven to be effective in the treatment of post-traumatic stress disorder (PTSD). However, there is still room for improvement because not all patients benefit from trauma-focused treatments. Improvements in the treatment of PTSD can be achieved by investigating ways to enhance existing therapies, such as eye movement desensitization and reprocessing (EMDR) therapy, as well as exploring novel treatments. The purpose of the current study is to determine the differential effectiveness, efficiency, and acceptability of EMDR therapy, an adaptation of EMDR therapy, referred to as EMDR 2.0, and a novel intervention for PTSD, the so-called Flash technique. The second aim is to identify the moderators of effectiveness for these interventions. This study will be conducted among individuals diagnosed with PTSD using a randomized controlled trial design.

Methods

A total of 130 patients diagnosed with (complex) PTSD will be randomly allocated to either six sessions of EMDR therapy, EMDR 2.0, or the Flash technique. The primary outcomes used to determine treatment effectiveness include the presence of a PTSD diagnosis and the severity of PTSD symptoms. The secondary outcomes of effectiveness include symptoms of depression, symptoms of dissociation, general psychiatric symptoms, and experiential avoidance. All patients will be assessed at baseline, at 4-week post-treatment, and at 12-week follow-up. Questionnaires indexing symptoms of PTSD, depression, general psychopathology, and experiential avoidance will also be assessed weekly during treatment and bi-weekly after treatment, until the 12-week follow-up. Efficiency will be assessed by investigating the time it takes both to lose the diagnostic status of PTSD, and to achieve reliable change in PTSD symptoms. Treatment acceptability will be assessed after the first treatment session and after treatment termination.

Discussion

This study is the first to investigate EMDR 2.0 therapy and the Flash technique in a sample of participants officially diagnosed with PTSD using a randomized controlled trial design. This study is expected to improve the available treatment options for PTSD and provide therapists with alternative ways to choose a therapy beyond its effectiveness by considering moderators, efficiency, and acceptability.

Trial registration

The trial was retrospectively registered in the ISRCTN registry at 10th November 2022 under registration number ISRCTN13100019.
Cost-effectiveness of non-communicable disease prevention in Southeast Asia: a scoping review
Authors: Nguyen Thi-Phuong-Lan , Rokhman M. Rifqi , Stiensma Imre , Hanifa Rachmadianti Sukma , Ong The Due , Postma Maarten J. , van der Schans Jurjen
Published: November 2023

Background

Cost-effectiveness analyses (CEAs) on prevention of non-communicable diseases (NCDs) are necessary to guide decision makers to allocate scarce healthcare resource, especially in Southeast Asia (SEA), where many low- and middle-income countries (LMICs) are in the process of scaling-up preventive interventions. This scoping review aims to summarize the cost-effectiveness evidence of primary, secondary, or tertiary prevention of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) as well as of major NCDs risk factors in SEA.

Methods

A scoping review was done following the PRISMA checklist for Scoping Reviews. Systematic searches were performed on Cochrane Library, EconLit, PubMed, and Web of Science to identify CEAs which focused on primary, secondary, or tertiary prevention of T2DM, CVDs and major NCDs risk factors with the focus on primary health-care facilities and clinics and conducted in SEA LMICs. Risks of bias of included studies was assessed using the Consensus of Health Economic Criteria list.

Results

This study included 42 CEAs. The interventions ranged from screening and targeting specific groups for T2DM and CVDs to smoking cessation programs, discouragement of smoking or unhealthy diet through taxation, or health education. Most CEAs were model-based and compared to a do-nothing scenario. In CEAs related to tobacco use prevention, the cost-effectiveness of tax increase was confirmed in all related CEAs. Unhealthy diet prevention, mass media campaigns, salt-reduction strategies, and tax increases on sugar-sweetened beverages were shown to be cost-effective in several settings. CVD prevention and treatment of hypertension were found to be the most cost-effective interventions. Regarding T2DM prevention, all assessed screening strategies were cost-effective or even cost-saving, and a few strategies to prevent T2DM complications were found to be cost-effective in certain settings.

Conclusion

This review shows that the cost-effectiveness of preventive strategies in SEA against T2DM, CVDs, and their major NCDs risk factors are heterogenous in both methodology as well as outcome. This review combined with the WHO “best buys” could guide LMICs in SEA in possible interventions to be considered for implementation and upscaling. However, updated and country-specific information is needed to further assess the prioritization of the different healthcare interventions.

Systematic review registration

https://osf.io, identifier: 10.17605/OSF.IO/NPEHT.
Addressing unforeseen public health risks via the use of sustainable system and process management
Authors: Zhang Yi , Yu Yue , Fong Patrick Sik Wah , Shen Jianfu
Published: November 2023

During the coronavirus disease 2019 (COVID-19) pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was designated by the World Health Organization in January 2020 as a newly emerging coronavirus in 2019, and its variants have placed unbearable strain on the healthcare systems of various countries, with serious implications for sustainable development worldwide. Researchers have proposed several solutions, such as the use of digital technologies to improve prevention systems. However, the challenges of epidemic prevention and control failures have not been addressed fundamentally, as the key causes of epidemic failures (i.e., outbreaks) and strategies for process management have been neglected. The purpose of the current study is to address these issues by exploring the causes of epidemic prevention and control failure and targeting improvement strategies that combine system structure of epidemic prevention and process management. Specifically, following an exploration of the main reasons for COVID-19 prevention and control failures through a case study of two tertiary hospitals, this paper outlines a targeted prevention and control system based on triangular validation and a loosely coupled process management framework and verifies the expected results using simulation methods together with statistical data on the spread of SARS-CoV-2 in Wuhan, China. The findings not only advance the development of epidemic risk prevention and control theory, especially the complementary nature of IT applications and process management in the field of epidemic risk prevention and control, but also provide guidance on the innovation and implementation of epidemic prevention and control systems and process management and recommendations for countries to promote sustainable development from a health-focused perspective.