bluuebunny/crossref_metadata_2025 huggingface dataset:
My hands are running away – learning a complex nursing skill via virtual reality simulation: a randomised mixed methods study
Authors: Plotzky Christian , Loessl Barbara , Kuhnert Barbara , Friedrich Nina , Kugler Christiane , König Peter , Kunze Christophe
Published: June 2023

Background

Clinical skills training is an essential component of nursing education. However, sometimes education does not sufficiently prepare nurses for the real world. Virtual reality (VR) is an innovative method to complement existing learning strategies, yet few studies investigate its effectiveness. This study compared educational outcomes achieved by three groups learning with either of two different VR simulation variants, with varying technological features, or a video training on the endotracheal suctioning skill.

Methods

The investigated outcomes were knowledge and skill acquisition, learner satisfaction, and technology acceptance. 131 undergraduate nursing students were randomised into three groups, based on the interventions they received. Knowledge was assessed through a pre-post-test design, skill through a post-intervention objective structured clinical examination on a manikin, learning satisfaction and technology acceptance through standardised questionnaires, and qualitative feedback through focus groups.

Results

All interventions led to a significant knowledge acquisition, with no significant difference between the groups. The video intervention group performed significantly better than the VR groups in skill demonstration. One of the two VR intervention groups had a significantly higher learner satisfaction than the video group. Technology acceptance was high for both VR groups, with the simpler VR simulation resulting in higher technology acceptance than the one with more experimental features. Students described the VR experience as realistic, interactive, and immersive, and saw the opportunity to practise skills in a safe environment, learn from mistakes, and increase knowledge and confidence.

Conclusions

For the development of VR trainings, we recommend keeping them simple and targeting a specific educational outcome since trying to optimise for multiple outcomes is resource intensive and hard to achieve. Psychomotor skills were easier for participants to learn by watching a video on the procedure rather than practically learning it with the VR hardware, which is a more abstract representation of reality. We therefore recommend using VR as a complementing resource to skills labs, rather than replacing existing learning strategies. Perhaps VR is not ideal for practising practical psychomotor skills at the moment, but it can increase knowledge, satisfaction, motivation, confidence and prepare for further practical training.

Trial registration

Not applicable.
Promoter hypermethylation and comprehensive regulation of ncRNA lead to the down-regulation of ZNF880, providing a new insight for the therapeutics and research of colorectal cancer
Authors: Dong Xiangqian , Zhang Yinghui , Sun Yang , Nan Qiong , Li Maojuan , Ma Lanqing , Zhang Lei , Luo Juan , Qi Yating , Miao Yinglei
Published: June 2023

The human genome encodes more than 350 kinds of Krüppel-associated box (KRAB) domain-containing zinc-finger proteins (KZFPs), KRAB-type ZNF transcription factor family (KZNF) plays a vital role in gene regulatory networks. The KZNF family members include a large number of highly homologous genes, gene subtypes and pseudogenes, and their expression has a high degree of tissue specificity and precision. Due to the high complexity of its regulatory network, the KZNF gene family has not been researched in sufficient, and the role of its members in the occurrence of cancer is mostly unexplored. In this study, ZNF880 was significantly associated with overall survival (OS) and disease-free survival (DFS) in colorectal carcinoma (CRC) patients. Low ZNF880 expression resulted in shorter OS and DFS. Combined with Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) data collection in the TCGA database, we found that ZNF880 was significantly down-regulated in CRC. Further analysis of the sequence variation of ZNF880 in CRC showed that ZNF880 accumulated a large number of SNV in the C2H2 domain and KRAB domain, while promoter region of ZNF880 also showed high methylation in COAD and READ. Combined with the Cbioportal and TIMER databases, the expression of mutant ZNF880 was significantly lower in COAD compared to the wild type. Simultaneously, the lncRNA-miRNA-ZNF880 ceRNA regulatory network was constructed through co-expression and miRNAs target gene prediction, demonstrating the precision of the ZNF880 regulatory network. In addition, the decreased expression of ZNF880 caused the significant immune infiltration decreases of CD8 + cells in COAD. In contrast, the immune infiltration of CD4 + cells and macrophages in COAD is positively correlated with ZNF880. Finally, through protein–protein interaction (PPI) network analysis and transcription factor target gene prediction, we screened out the genes most likely to be related to the function of ZNF880. CENPK, IFNGR2, REC8 and ZBTB17 were identified as the most closely functioning genes with ZNF880, which may indicate that ZNF880 has important links with the formation of cell centromere, tumor immunity, cell cycle and other pathways closely related to the occurrence of CRC. These studies show that the down-regulation of ZNF880 gene is closely related to CRC, and the targeted change of the expression of its regulatory molecules (miRNA and lncRNA) may be a new perspective for CRC treatment.
Accuracy of intravascular ultrasound-derived virtual fractional flow reserve (FFR) and FFR derived from computed tomography for functional assessment of coronary artery disease
Authors: Huang Wenhao , Zhang Jingyuan , Yang Lin , Hu Yumeng , Leng Xiaochang , Liu Yajun , Jin Hongfeng , Tang Yiming , Wang Jiangting , Liu Xiaowei , Guo Yitao , Ye Chen , Feng Yue , Xiang Jianping , Tang Lijiang , Du Changqing
Published: June 2023

Background

Coronary computed tomography-derived fractional flow reserve (CT-FFR) and intravascular ultrasound-derived fractional flow reserve (IVUS-FFR) are two functional assessment methods for coronary stenoses. However, the calculation algorithms for these methods differ significantly. This study aimed to compare the diagnostic performance of CT-FFR and IVUS-FFR using invasive fractional flow reserve (FFR) as the reference standard.

Methods

Six hundred and seventy patients (698 lesions) with known or suspected coronary artery disease were screened for this retrospective analysis between January 2020 and July 2021. A total of 40 patients (41 lesions) underwent intravascular ultrasound (IVUS) and FFR evaluations within six months after completing coronary CT angiography were included. Two novel CFD-based models (AccuFFRct and AccuFFRivus) were used to compute the CT-FFR and IVUS-FFR values, respectively. The invasive FFR ≤ 0.80 was used as the reference standard for evaluating the diagnostic performance of CT-FFR and IVUS-FFR.

Results

Both AccuFFRivus and AccuFFRct demonstrated a strong correlation with invasive FFR (R = 0.7913, P < 0.0001; and R = 0.6296, P < 0.0001), and both methods showed good agreement with FFR. The area under the receiver operating characteristic curve was 0.960 (P < 0.001) for AccuFFRivus and 0.897 (P < 0.001) for AccuFFRct in predicting FFR ≤ 0.80. FFR ≤ 0.80 were predicted with high sensitivity (96.6%), specificity (85.7%), and the Youden index (0.823) using the same cutoff value of 0.80 for AccuFFRivus. A good diagnostic performance (sensitivity 89.7%, specificity 85.7%, and Youden index 0.754) was also demonstrated by AccuFFRct.

Conclusions

AccuFFRivus, computed from IVUS images, exhibited a high diagnostic performance for detecting myocardial ischemia. It demonstrated better diagnostic power than AccuFFRct, and could serve as an accurate computational tool for ischemia diagnosis and assist in clinical decision-making.
Mutated CYP17A1 promotes atherosclerosis and early-onset coronary artery disease
Authors: Wu Ting-Ting , Zheng Ying-Ying , Ma Xiang , Xiu Wen-Juan , Yang Hai-Tao , Hou Xian-Geng , Yang Yi , Chen You , Ma Yi-Tong , Xie Xiang
Published: June 2023

Background

Coronary artery disease (CAD) is a multi-factor complex trait and is heritable, especially in early-onset families. However, the genetic factors affecting the susceptibility of early-onset CAD are not fully characterized.

Methods

In the present study, we identified a rare nonsense variant in the CYP17A1 gene from a Chinese Han family with CAD. To validate the effect of this variation on atherosclerosis and early-onset coronary artery disease, we conducted studies on population, cells, and mice.

Results

The mutation precisely congregated with the clinical syndrome in all the affected family members and was absent in unaffected family members and unrelated controls. Similar to the human phenotype, the CYP17A1-deficient mice present the phenotype of metabolic syndrome with hypertension, increased serum glucose concentration, and presentation of central obesity and fatty liver. Furthermore, CYP17A1 knockout mice or CYP17A1 + ApoE double knockout mice developed more atherosclerotic lesions than wild type (WT) with high fat diary. In cell models, CYP17A1 was found to be involved in glucose metabolism by increasing glucose intake and utilization, through activating IGF1/mTOR/HIF1-α signaling way, which was consistent in CYP17A1 knockout mice with impaired glucose tolerance and insulin resistance.

Conclusions

Through our study of cells, mice and humans, we identified CYP17A1 as a key protein participating in the pathophysiology of the atherosclerotic process and the possible mechanism of CYP17A1 C987X mutation induced atherosclerosis and early-onset CAD involving glucose homeostasis regulation was revealed.
Cancer stem cell fate determination: mito-nuclear communication
Authors: Fan Mengchen , Shi Ying , Zhao Jumei , Li Ling
Published: June 2023

Cancer stem cells (CSCs) are considered to be responsible for tumor recurrence and metastasis. Therefore, clarification of the mechanisms involved in CSC stemness maintenance and cell fate determination would provide a new strategy for cancer therapy. Unregulated cellular energetics has been accepted as one of the hallmarks of cancer cells, but recent studies have revealed that mitochondrial metabolism can also actively determine CSC fate by affecting nuclear stemness gene expression. Herein, from the perspective of mito-nuclear communication, we review recent progress on the influence of mitochondria on CSC potential from four aspects: metabolism, dynamics, mitochondrial homeostasis, and reactive oxygen species (ROS).
The crescent-like Golgi ribbon is shaped by the Ajuba/PRMT5/Aurora-A complex-modified HURP
Authors: Chiu Shao-Chih , Yang Xin-Ting , Wei Tong-You Wade , Liao Yu-Ting Amber , Chen Jo-Mei Maureen , Kuo Yi-Chun , Liu Chun-Chih Jared , Cheng Chiao-Yun , Huang Yu-Ting Jenny , Huang Yun-Ru Jaoying , Wu He-Lian Joe , Wan Chang-Xin , Tsai Jia-Rung , Yu Chang-Tze Ricky
Published: June 2023

Background

Golgi apparatus (GA) is assembled as a crescent-like ribbon in mammalian cells under immunofluorescence microscope without knowing the shaping mechanisms. It is estimated that roughly 1/5 of the genes encoding kinases or phosphatases in human genome participate in the assembly of Golgi ribbon, reflecting protein modifications play major roles in building Golgi ribbon.

Methods

To explore how Golgi ribbon is shaped as a crescent-like structure under the guidance of protein modifications, we identified a protein complex containing the scaffold proteins Ajuba, two known GA regulators including the protein kinase Aurora-A and the protein arginine methyltransferase PRMT5, and the common substrate of Aurora-A and PRMT5, HURP. Mutual modifications and activation of PRMT5 and Aurora-A in the complex leads to methylation and in turn phosphorylation of HURP, thereby producing HURP p725. The HURP p725 localizes to GA vicinity and its distribution pattern looks like GA morphology. Correlation study of the HURP p725 statuses and GA structure, site-directed mutagenesis and knockdown-rescue experiments were employed to identify the modified HURP as a key regulator assembling GA as a crescent ribbon.

Results

The cells containing no or extended distribution of HURP p725 have dispersed GA membranes or longer GA. Knockdown of HURP fragmentized GA and HURP wild type could, while its phosphorylation deficiency mutant 725A could not, restore crescent Golgi ribbon in HURP depleted cells, collectively indicating a crescent GA-constructing activity of HURP p725. HURP p725 is transported, by GA membrane-associated ARF1, Dynein and its cargo adaptor Golgin-160, to cell center where HURP p725 forms crescent fibers, binds and stabilizes Golgi assembly factors (GAFs) including TRIP11, GRASP65 and GM130, thereby dictating the formation of crescent Golgi ribbon at nuclear periphery.

Conclusions

The Ajuba/PRMT5/Aurora-A complex integrates the signals of protein methylation and phosphorylation to HURP, and the HURP p725 organizes GA by stabilizing and recruiting GAFs to its crescent-like structure, therefore shaping GA as a crescent ribbon. Therefore, the HURP p725 fiber serves a template to construct GA according to its shape.
The impact of lipid metabolism on breast cancer: a review about its role in tumorigenesis and immune escape
Authors: Zipinotti dos Santos Diandra , de Souza Josiany Carlos , Pimenta Tatiana Massariol , da Silva Martins Bárbara , Junior Roberto Silva Ribeiro , Butzene Solenny Maria Silva , Tessarolo Nayara Gusmão , Cilas Paulo Morais Lyra , Silva Ian Victor , Rangel Leticia B. A.
Published: June 2023

Background

Breast cancer (BC) is the second most frequent type of cancer in the world and most common among women, configuring a major challenge to global health. BC is a complex and heterogeneous disease that can be subdivided into distinct tumor types based on the expression of molecular markers predicting patient outcomes and response to therapy. A growing number of studies have tried to expand the known markers by investigating the association of altered lipid metabolism with BC immune escape, progression, and metastasis. In this review, we describe the metabolic peculiarities of each BC subtype, understanding how this influences its aggressiveness and identifying whether these intrinsic vulnerabilities of each subtype can play a role in therapeutic management and may affect immune system cells in the tumor microenvironment.

Conclusion

The evidence suggests so far that when changes occur in lipid pathways, it can affect the availability of structural lipids for membrane synthesis, lipid synthesis, and degradation that contribute to energy homeostasis and cell signaling functions. These findings will guide the next steps on the path to understanding the mechanisms underlying how lipids alterations are related to disparities in chemotherapeutic response and immune escape in BC.
Non-POU Domain-Containing Octomer-Binding (NONO) protein expression and stability promotes the tumorigenicity and activation of Akt/MAPK/β-catenin pathways in human breast cancer cells
Authors: Lone Bilal Ahmad , Siraj Fouzia , Sharma Ira , Verma Shweta , Karna Shibendra Kumar Lal , Ahmad Faiz , Nagar Preeti , Sachidanandan Chetana , Pokharel Yuba Raj
Published: June 2023

Breast cancer is one of the most common cancers with a high mortality rate, underscoring the need to identify new therapeutic targets. Here we report that non-POU domain-containing octamer-binding (NONO) protein is overexpressed in breast cancer and validated the interaction of the WW domain of PIN1 with c-terminal threonine-proline (thr-pro) motifs of NONO. The interaction of NONO with PIN1 increases the stability of NONO by inhibiting its proteasomal degradation, and this identifies PIN1 as a positive regulator of NONO in promoting breast tumor development. Functionally, silencing of NONO inhibits the growth, survival, migration, invasion, epithelial to mesenchymal transition (EMT), and stemness of breast cancer cells in vitro. A human metastatic breast cancer cell xenograft was established in transparent zebrafish (Danio rerio) embryos to study the metastatic inability of NONO-silenced breast cancer cells in vivo. Mechanistically, NONO depletion promotes the expression of the PDL1 cell-surface protein in breast cancer cells. The identification of novel interactions of NONO with c-Jun and β-catenin proteins and activation of the Akt/MAPK/β-catenin signaling suggests that NONO is a novel regulator of Akt/MAPK/β-catenin signaling pathways. Taken together, our results indicated an essential role of NONO in the tumorigenicity of breast cancer and could be a potential target for anti-cancerous drugs.
RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3
Authors: Shi Qian , He Ying , He Shouyu , Li Jingjing , Xia Ji , Chen Tianwei , Huo Lixia , Ling Yuhang , Liu Qinchen , Zang Wei , Wang Qiang , Tang Chengwu , Wang Xiang
Published: June 2023

Background

RP11-296E3.2 is a novel long noncoding RNA (lncRNA) associated with colorectal cancer (CRC) metastasis, that was reported in our previous clinical studies. However, the mechanisms of RP11-296E3.2 in colorectal tumorigenesis remain elusive.

Methods

RNA sequencing (RNA-seq), Fluorescence in situ hybridization (FISH), Transwell assays and others, were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vitro. In situ and metastatic tumor models were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vivo. RNA-pulldown, RNA-interacting protein immunoprecipitation (RIP), tissue microarray (TMA) assay, a luciferase reporter assay, chromatin immunoprecipitation (ChIP) and others were performed to explore the mechanisms by which RP11-296E3.2 regulates CRC tumorigenesis.

Results

RP11-296E3.2 was confirmed to be associated with CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, RP11-296E3.2 directly bound to recombinant Y-Box Binding Protein 1 (YBX1) and enhanced signal transducer and activator of transcription 3 (STAT3) transcription and phosphorylation. YBX1 promoted the CRC cell proliferation and migration, while knockdown of RP11-296E3.2 attenuated the effects of YBX1 on CRC cell proliferation, and metastasis and the expression of several related downstream genes. We are the first to discover and confirm the existence of the YBX1/STAT3 pathway, a pathway dependent on RP11-296E3.2.

Conclusion

Together, these novel findings show that the RP11-296E3.2/YBX1 pathway promotes colorectal tumorigenesis and progression by activating STAT3 transcription and phosphorylation, and suggest that RP11-296E3.2 is a potential diagnostic biomarker and therapeutic target in CRC.
Is chewing khat associated with mental health disorders? A scoping review of the content and quality of the current evidence base
Authors: Olani Amanti Baru , Gerbaba Mulusew , Getnet Masrie , Soboka Matiwos , Decorte Tom
Published: June 2023

Background

Khat (Catha edulis) is a plant commonly found in the horn of Africa whose leaves are chewed for their psycho-stimulant effects. Several studies have demonstrated the association between khat use and mental health problems. Nevertheless, evidence is mixed and inconsistent, warranting further review of available studies. This scoping review is aimed at investigating the content and quality of evidence base on the associations between khat use and mental health disorders and suggesting avenues for further research.

Methods

We used a scoping review methodology to map the existing evidence using PubMed, SCOPUS, Embase, and CINAHL databases. Primary studies focusing on the association between any pattern of khat use and any form of mental health disorders are included. The review focused on all age groups, any study design, all geographical locations, and any publication year. The terms used for searching eligible studies include khat, mental disorders, and various alternative terminologies. Narrative review is employed to present findings.

Results

7,121 articles were found, of which 108 were eligible, conducted across 12 different countries. The majority of the studies was done during the last ten years and the studies mostly employed cross-sectional design. About 10 different categories of mental health disorders have been identified as showing associations with khat use. Despite many contradictory findings between the studies, most of the evidence base suggests that khat use is associated with mental health disorders. Non-specific psychological distress is the most frequently mentioned mental health problem (reported in 26.9% of the studies). Khat use as a predictor variable is mostly assessed using a ‘yes/no’ category, and as a result, dose-dependent effects of khat use on mental health are not given much consideration.

Conclusion

Although most of the studies associate khat use with mental health disorders, the causal relationships are inconclusive given the cross-sectional design of the studies, and the presence of potential confounders and several forms of biases. Available studies also report contradictory findings. Further studies are recommended using prospective designs, standardized and valid measures of khat use, and focusing on specific types of mental health disorders.
The validity and reliability of the Arabic version of the short form of neurogenic bladder symptoms score in patients with spinal cord injury
Authors: Khadour Younes A. , Zheng Meng , Khadour Fater A.
Published: June 2023

Background

The Neurogenic Bladder Symptom Score-Short Form (NBSS-SF) evaluates the impact of disease-specific symptoms on the quality of life in individuals with neurogenic bladder (NB). There is no data on the validity and reliability of the NBSS-SF questionnaire in the Arabic language, so this study aimed to examine the psychometric characteristics of the Arabic NBSS-SF in patients with spinal cord injury (SCI).

Methods

International standards were followed when culturally adapting the questionnaire. The Arabic version was conducted in patients with neurogenic bladder caused by SCI twice within a 14 day period. Psychometric properties such as content validity, construct validity, internal consistency, and test–retest reliability were tested. Internal consistency and test–retest reliability was evaluated using Cronbach’s alpha, and the Intraclass Correlation Coefficient (ICC), respectively. Construct validity was assessed by comparing the NBSS-SF with the Short Form (SF-12) and the Qualiveen questionnaire.

Results

One hundred and one patients with SCI participated in the study. The internal consistency for the overall NBSS-SF score (Cronbach’s α of 0.82) and for each subdomain was variable (urinary incontinence 0.84; storage/voiding 0.72; consequences 0.57). ICC was 0.91 for the overall score and 0.94 for the urinary incontinence subdomain, 0.72 for storage/voiding, and 0.90 for consequences. The correlation analysis showed that the Arabic version of NBSS-SF has good construct validity.

Conclusion

Our results showed that the Arabic version of NBSS-SF is a valid and reliable instrument for evaluating NB symptoms in the Arabic population suffering from SCI.
The lateral habenula nucleus regulates pruritic sensation and emotion
Authors: Chen Rui , Xu Xiang , Wang Xin-Yue , Jia Wen-Bin , Zhao De-Shan , Liu Na , Pang Zhen , Liu Xiao-Qing , Zhang Yan
Published: June 2023

Itch is a complex aversive sensory and emotional experience. As a most upsetting symptom in many dermatological and systemic diseases, it lacks efficient treatments. The lateral habenula nucleus (LHb) encodes negative emotions in the epithalamus and has been implicated in pain and analgesia. Nevertheless, the role of the lateral habenula nucleus in the pruritic sensation and emotion remains elusive. Here we defined the crucial role of glutamatergic neurons within the lateral habenula nucleus (GluLHb) in itch modulation in mice. We established histamine-dependent and histamine-independent models of acute pruritus, as well as the acetone-ether-water (AEW) model of chronic pruritus. We first assessed the effects of pruritogen injection on neural activation in both medial and lateral divisions of LHb in vitro. We then demonstrated that the population activity of GluLHb neurons was increased during the acute itch and chronic itch-induced scratching behaviors in vivo. In addition, electrophysiological data showed that the excitability of GluLHb neurons was enhanced by chronic itch. Chemogenetic suppression of GluLHb neurons disrupted both acute and chronic itch-evoked scratching behaviors. Furthermore, itch-induced conditioned place aversion (CPA) was abolished by GluLHb neuronal inhibition. Finally, we dissected the LHb upstream brain regions. Together, these findings reveal the involvement of LHb in processing both the sensational and emotional components of pruritus and may shed new insights into itch therapy.
Development and validation of a nomogram to predict cancer-specific survival of mucinous epithelial ovarian cancer after cytoreductive surgery
Authors: Ma Guanchen , Zeng Shaoqing , Zhao Yingjun , Chi Jianhua , Wang Li , Li Qingshui , Wang Jing , Yao Shuzhong , Zhou Qi , Chen Youguo , Jiao Xiaofei , Liu Xingyu , Yu Yang , Huo Yabing , Li Ming , Peng Zikun , Ma Ding , Hu Ting , Gao Qinglei
Published: June 2023

Background

Mucinous epithelial ovarian cancer (mEOC) is a relatively uncommon subtype of ovarian cancer with special prognostic features, but there is insufficient research in this area. This study aimed to develop a nomogram for the cancer-specific survival (CSS) of mEOC based on Surveillance, Epidemiology, and End Results (SEER) database and externally validate it in National Union of Real World Gynecological Oncology Research and Patient Management (NUWA) platform from China.

Methods

Patients screened from SEER database were allocated into training and internal validation cohort in a ratio of 7: 3, with those from NUWA platform as an external validation cohort. Significant factors selected by Cox proportional hazard regression were applied to establish a nomogram for 3-year and 5-year CSS. The performance of nomogram was assessed by concordance index, calibration curves and Kaplan-Meier (K-M) curves.

Results

The training cohort (n = 572) and internal validation cohort (n = 246) were filtered out from SEER database. The external validation cohort contained 186 patients. Baseline age, tumor stage, histopathological grade, lymph node metastasis and residual disease after primary surgery were significant risk factors (p < 0.05) and were included to develop the nomogram. The C-index of nomogram in training, internal validation and external validation cohort were 0.869 (95% confidence interval [CI], 0.838-0.900), 0.839 (95% CI, 0.787–0.891) and 0.800 (95% CI, 0.738–0.862), respectively. The calibration curves of 3-year and 5-year CSS in each cohort showed favorable agreement between prediction and observation. K-M curves of different risk groups displayed great discrimination.

Conclusion

The discrimination and goodness of fit of the nomogram indicated its satisfactory predictive value for the CSS of mEOC in SEER database and external validation in China, which implies its potential application in different populations.
Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-β/Smads signaling pathway
Authors: Nazdikbin Yamchi Nahideh , Ahmadian Shahin , Mobarak Halimeh , Amjadi Farhad , Beheshti Rahim , Tamadon Amin , Rahbarghazi Reza , Mahdipour Mahdi
Published: June 2023

In the current study, we investigated the regenerative effects of amniotic fluid exosomes (AF-Exos) in a rat model for premature ovarian insufficiency (POI). POI is a condition characterized by a decrease in ovarian function that can lead to infertility. We induced POI by administering cyclophosphamide (CTX) for 15 consecutive days, and then transplanted AF-Exos directly into both ovarian tissues. Four weeks later, we measured the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2), and performed histopathological evaluations using H & E and Masson’s trichrome staining. We also monitored the expression of genes related to the TGF-β signaling pathway using real-time PCR and examined the fertility rate of POI rats after AF-Exos therapy. Histological analysis showed an increase in atretic follicles and a decrease in healthy follicle count after POI induction. Four weeks post-AF-Exos intervention, the healthy follicle count increased (p < 0.01) while the atretic follicle count decreased (p < 0.001). In parallel, the deposition of collagen fibers also decreased following AF-Exos transplantation. The concentrations of FSH and LH hormones in sera remained unchanged after injection of AF-Exos, while E2 levels increased (p < 0.05). The expression of Smad-4 (p < 0.01) and Smad-6 (p < 0.05) was upregulated in POI rats that received AF-Exos, while Smad-2, TGF-β1, TNF-α, and IL-10 remained statistically unchanged. Our records showed a notable increase in litter number after AF-Exos compared to the non-treated POI rats. These results suggest that AF-Exos transplantation has the potential to restore ovarian function through the TGF-β/Smads signaling pathway in POI rats.
Predictors of participant retention in a community-based HIV prevention cohort: perspectives from the HPTN 071 (PopART) study
Authors: Bell-Mandla Nomtha , Wilson Ethan , Sharma Deeksha , Sloot Rosa , Bwalya Justin , Schaap Ab , Donnell Deborah , Piwowar-Manning Estelle , Floyd Sian , Makola Nozizwe , Nkonki Lungiswa , Simwinga Musonda , Moore Ayana , Hayes Richard , Fidler Sarah , Ayles Helen , Bock Peter ,   the HPTN 071 (PopART) Study Team
Published: June 2023

Introduction

In 2021, there were 38.4 million people living with HIV (PLHIV) globally, of which 20.6 million (54%) were living in Eastern and Southern Africa. Longitudinal studies, inclusive of community randomized trials (CRTs), provide critical evidence to guide a broad range of health care interventions including HIV prevention. In this study, we have used an individual-level cohort study design to evaluate the association between sex and other baseline characteristics and participant retention in the HPTN 071 (PopART) trial in Zambia and South Africa.

Methods

HPTN 071 (PopART) was a community randomized trial (CRT) conducted from 2013 to 2018, in 21 communities. The primary outcome was measured in a randomly selected population cohort (PC), followed up over 3 to 4 years at annual rounds. PC retention was defined as completion of an annual follow-up questionnaire. Baseline characteristics were described by study arm and Poisson regression analyses used to measure the association between baseline factors and retention. In addition, we present a description of researcher-documented reasons for study withdrawal by PC participants.

Results

Of the 38,474 participants enrolled during the first round of the trial (PC0), most were women (27,139, 71%) and 73% completed at least one follow-up visit. Retention was lower in men (adj RR: 0.90; 95% CI: 0.88, 0.91) and higher among older participants (adj RR: 1.23; 95% CI 1.20, 1.26) when comparing ages 35–44 to 18–24 years. Retention was higher among individuals with high socioeconomic status (SES) (adj RR 1.16; 95% CI 1.14, 1.19) and medium SES (adj RR 1.12; 95% CI 1.09, 1.14) compared to low SES. The most common reasons for study withdrawal were study refusal (23%) and relocation outside the CRT catchment area (66%).

Conclusion

Despite challenges, satisfactory retention outcomes were achieved in PopART with limited variability across study arms. In keeping with other studies, younger age, male sex, and lower SES were associated with lower levels of retention. Relocation outside of catchment area was the most common reason for non-retention in this CRT.
Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn’s disease (ENDOCIR study): an open-label, multicentre, randomized trial
Authors: Loras Carme , Ruiz-Ramirez Pablo , Romero Juan , Andújar Xavier , Bargallo Josep , Bernardos Esther , Boscá-Watts Marta Maia , Brugiotti Carlo , Brunet Eduard , Busquets David , Cerrillo Elena , Cortina Francisco Javier , Díaz-Milanés Juan Antonio , Dueñas Carmen , Farrés Ramón , Golda Thomas , González-Huix Ferran , Gornals Joan B. , Guardiola Jordi , Julià David , Lira Alba , Llaó Jordina , Mañosa Miriam , Marin Ingrid , Millán Mónica , Monfort David , Moro David , Mullerat Josep , Navarro Mercè , Pérez Roldán Francisco , Pijoan Eva , Pons Vicente , Reyes José , Rufas María , Sainz Empar , Sanchiz Vicente , Serracant Anna , Sese Eva , Soto Cristina , Troya Jose , Zaragoza Natividad , Tebé Cristian , Paraira Marta , Sudrià-Lopez Emma , Mayor Vicenç , Fernández-Bañares Fernando , Esteve Maria ,   on behalf of the Grupo Español de Trabajo de la Enfermedad de Crohn y Colitis Ulcerosa GETECCU
Published: June 2023

Background

Stenosis is one of the most common complications in patients with Crohn’s disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length.

Methods/design

Exploratory study as “proof-of-concept”, multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up.

Discussion

The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD.

Trial registration

ClinicalTrials.gov NCT 04330846. Registered on 1 April 1 2020. https://clinicaltrials.gov/ct2/home
Epidemiology of soil-transmitted helminths using quantitative PCR and risk factors for hookworm and Necator americanus infection in school children in Dak Lak province, Vietnam
Authors: Hughes Angus , Ng-Nguyen Dinh , Clarke Naomi E. , Dyer Clare E. F. , Hii Sze Fui , Clements Archie C. A. , Anderson Roy M. , Gray Darren J. , Coffeng Luc E. , Kaldor John M. , Traub Rebecca J. , Vaz Nery Susana
Published: June 2023

Background

Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water, sanitation and hygiene (WASH). Epidemiological studies that measure both infection and potential risk factors associated with infection help to understand the drivers of transmission in a population and therefore can provide information to optimise STH control programmes.

Methods

During October and November 2019, we conducted a cross-sectional survey of the prevalence and intensity of STH infection and associated risk factors among 7710 primary-school-age children from 64 primary schools across 13 districts in Dak Lak province, Vietnam. Quantitative PCR (qPCR) was used to detect and quantify STH infections.

Results

The predominant STH species was the hookwormNecator americanus(overall cluster-adjusted prevalence of 13.7%), and its prevalence was heterogeneously distributed across surveyed schools (0% to 56.3%). All other STH species had a prevalence of less than 1%. Using mixed-effects logistic regression, we found that the adjusted odds ratio (aOR) was significantly higher for both infection and moderate-to-heavy-intensity infection withN. americanusamong children from multiple ethnic minority groups, compared to children from the majority group (Kinh). Adjusted odds of infection withN. americanuswere also higher in children who reported practising open defecation at school (aOR 1.42, 95% CI 1.05, 1.93,P = 0.02) and in those who had an unimproved household water supply (aOR 1.28, 95% CI 1.04, 1.57,P = 0.02). Conversely, children with a flushing household toilet had a reduced risk of infection (aOR 0.58, 95% CI 0.47, 0.70,P < 0.01), as did those whose primary female carer attended secondary (aOR 0.65, 95% CI 0.51, 0.84,P < 0.01) or tertiary education (aOR 0.39, 95% CI 0.24, 0.63,P < 0.01).

Conclusions

This study is the largest reported prevalence survey of STH infections conducted using qPCR as a diagnostic technique. The findings of higher adjusted odds of infection amongst ethnic minority children highlight that STH control programmes may not be reaching certain population groups and that additional culturally appropriate approaches may be required. Additionally, the associations between specific WASH factors and infection indicate potential programmatic targets to complement preventive chemotherapy programmes.

Graphical Abstract
A chromosome scale assembly of the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), genome
Authors: Perera O. P. , Saha Surya , Glover James , Parys Katherine A. , Allen K. Clint , Grozeva Snejana , Kurtz Ryan , Reddy Gadi V. P. , Johnston J. Spencer , Daly Mark , Swale Thomas
Published: June 2023

Objective

The tarnished plant bug (TPB), Lygus lineolaris (Palisot de Beauvois) (Hemiptera: Miridae), is a pest damaging many cultivated crops in North America. Although partial transcriptome data are available for this pest, a genome assembly was not available for this species. This assembly of a high-quality chromosome-length genome of TPB is aimed to develop the genetic resources that can provide the foundation required for advancing research on this species.

Results

The initial genome of TPB assembled with paired-end nucleotide sequences generated with Illumina technology was scaffolded with Illumina HiseqX reads generated from a proximity ligated (HiC) library to obtain a high-quality genome assembly. The final assembly contained 3963 scaffolds longer than 1 kbp to yield a genome of 599.96 Mbp. The N50 of the TPB genome assembly was 35.64 Mbp and 98.68% of the genome was assembled into 17 scaffolds larger than 1 Mbp. This megabase scaffold number is the same as the number of chromosomes observed in karyotyping of this insect. The TPB genome is known to have high repetitive DNA content, and the reduced assembled genome size compared to flowcytometric estimates of approximately 860 Mbp may be due to the collapsed assembly of highly similar regions.
Polyetheretherketone implants with hierarchical porous structure for boosted osseointegration
Authors: Chen Zhiyong , Chen Yu , Wang Yang , Deng JiaJia , Wang Xin , Wang Qingqing , Liu Yuehua , Ding Jiandong , Yu Lin
Published: June 2023

Background

Good osseointegration is the key to the long-term stability of bone implants. Thermoplastic polyetheretherketone (PEEK) has been widely used in orthopedics; however, its inherent biological inertia causes fibrous tissue to wrap its surface, which leads to poor osseointegration and thus greatly limits its clinical applications.

Methods

Herein, we developed a facile yet effective surface modification strategy. A commonly used sulfonation coupled with “cold pressing” treatment in the presence of porogenic agent formed a three-dimensional hierarchical porous structure on PEEK surface. Subsequently, the effects of porous surface on the in vitro adhesion, proliferation and differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) were evaluated. Finally, the osteoinduction and osseointegration of surface-porous PEEK implant were examined in the rat distal femoral defect model.

Results

In vitro results showed that the surface modification did not significantly affect the mechanical performance and cytocompatibility of PEEK substance, and the porous structure on the modified PEEK substrate provided space for cellular ingrowth and enhanced osteogenic differentiation and mineralization of BMSCs. In vivo tests demonstrated that the surface-porous PEEK implant could effectively promote new bone formation and had higher bone-implant contact rate, thereby achieving good bone integration with the surrounding host bone. In addition, this modification technique was also successfully demonstrated on a medical PEEK interbody fusion cage.

Conclusion

The present study indicates that topological morphology plays a pivotal role in determining implant osseointegration and this facile and effective modification strategy developed by us is expected to achieve practical applications quickly.

Graphical Abstract
Hybrid control using fuzzy logic and adaptive space vector modulation for reduction of torque ripples in PM-BLDC motor drive
Authors: Karan Vijay Kumar , Alam Aftab , Thakur Amarnath
Published: June 2023

A novel hybrid control strategy for reducing torque ripple in permanent magnet brushless direct current motors has been developed by combining the deterministic nature of direct torque control and the adaptive nature of fuzzy logic control. Direct torque control using space vector pulse width modulation has been developed. This technique ensures the near-sinusoidal nature of the stator and rotor current. The impact of commutation ripple corresponding to the sinusoidal current is reduced compared to square wave current in conventional direct torque control. Further, the fuzzy logic controller provides adaptive modulation in space vector to mitigate the torque ripple. The response of the proposed method has been analyzed in the time domain as well as in the frequency domain. Experimental results establish a significant reduction in torque ripple and minimization of high-frequency components. A comparative study with conventional direct torque control methods has also been presented.
Pleiotropy of autism-associated chromatin regulators
Authors: Lasser Micaela , Sun Nawei , Xu Yuxiao , Wang Sheng , Drake Sam , Law Karen , Gonzalez Silvano , Wang Belinda , Drury Vanessa , Castillo Octavio , Zaltsman Yefim , Dea Jeanselle , Bader Ethel , McCluskey Kate E. , State Matthew W. , Willsey A. Jeremy , Willsey Helen Rankin
Published: June 2023

Gene ontology analyses of high-confidence autism spectrum disorder (ASD) risk genes highlight chromatin regulation and synaptic function as major contributors to pathobiology. Our recent functional work in vivo has additionally implicated tubulin biology and cellular proliferation. As many chromatin regulators, including the ASD risk genes ADNP and CHD3, are known to directly regulate both tubulins and histones, we studied the five chromatin regulators most strongly associated with ASD (ADNP, CHD8, CHD2, POGZ and KMT5B) specifically with respect to tubulin biology. We observe that all five localize to microtubules of the mitotic spindle in vitro in human cells and in vivo in Xenopus. Investigation of CHD2 provides evidence that mutations present in individuals with ASD cause a range of microtubule-related phenotypes, including disrupted localization of the protein at mitotic spindles, cell cycle stalling, DNA damage and cell death. Lastly, we observe that ASD genetic risk is significantly enriched among tubulin-associated proteins, suggesting broader relevance. Together, these results provide additional evidence that the role of tubulin biology and cellular proliferation in ASD warrants further investigation and highlight the pitfalls of relying solely on annotated gene functions in the search for pathological mechanisms.
Phosphorylation of Rab29 at Ser185 regulates its localization and role in the lysosomal stress response in concert with LRRK2
Authors: Komori Tadayuki , Kuwahara Tomoki , Fujimoto Tetta , Sakurai Maria , Koyama-Honda Ikuko , Fukuda Mitsunori , Iwatsubo Takeshi
Published: June 2023

Rab proteins are small GTPases that regulate a myriad of intracellular membrane trafficking events. Rab29 is one of the Rab proteins phosphorylated by leucine-rich repeat kinase 2 (LRRK2), a Parkinson's disease-associated kinase. Recent studies suggest that Rab29 regulates LRRK2, whereas the mechanism by which Rab29 is regulated remained unclear. Here, we report a novel phosphorylation in Rab29 that is not mediated by LRRK2 and occurs under lysosomal overload stress. Mass spectrometry analysis identified the phosphorylation site of Rab29 as Ser185, and cellular expression studies of phosphomimetic mutants of Rab29 at Ser185 unveiled the involvement of this phosphorylation in counteracting lysosomal enlargement. PKCα and PKCδ were deemed to be involved in this phosphorylation and control the lysosomal localization of Rab29 in concert with LRRK2. These results implicate PKCs in the lysosomal stress response pathway comprised of Rab29 and LRRK2, and further underscore the importance of this pathway in the mechanisms underlying lysosomal homeostasis.
Comparative evaluation of clinical performance, child and parental satisfaction of Bioflex, zirconia and stainless steel crowns in pediatric patients
Authors: Rahate Ishani , Fulzele Punit , Thosar Nilima
Published: June 2023

Background: Pediatric treatment is challenging in patients with early childhood caries. It is difficult due to the adjacency of pulp, miniature tooth size, and thin enamel compared to permanent dentition. Nowadays, aesthetics play an important role in managing decayed teeth, and children need treatment that includes full coverage crowns in either stainless steel or anesthetic crown in zirconia or the recently developed Bioflex crown. The Bioflex crowns are highly flexible and aesthetically preformed pediatric crowns with combined stainless steel and zirconia properties. This study aims to assess the clinical performance and child and parental satisfaction of Bioflex crowns compared to zirconia and stainless steel crowns.

Methods: In the current in-vivo comparison of Bioflex crowns with zirconia and stainless steel crowns, children aged three to seven years old will be selected, and 72 primary teeth requiring crowns will be randomly distributed into three groups,  n = 24: Group I:  Preformed stainless steel crown, control; Group II:  Preformed Bioflex crown; Group III: Preformed zirconia crown. Crowns will be evaluated for recurrent caries, plaque accumulation, restoration failure, gingival status opposing tooth wear, and clinicians and parental satisfaction at zero, three, six, and 12 months. Newly introduced aesthetic crowns will serve as a versatile alternative for restoring primary decayed teeth that over-performed aesthetic and conventional crowns.

Conclusions: The Bioflex crown will be assessed as a better aesthetic substitute for the future, and the satisfaction level of parents will be evaluated. 

Trial registration: CTRI registration number: CTRI/2023/05/052256; Date of registration: May 03, 2023.

Protocol version: Two; Date: April 22, 2023
Computer technologies in professional activity
Authors: Kuznecova Natal'ya , Morozkina Svetlana
Published: June 2023

The textbook reveals modern aspects of the use of computer technology in professional activities. The features of work in the main text and table processors are considered in detail, an overview of modern technologies of remote banking services, software products for accounting and analytical work is given.
Meets the requirements of the federal state educational standards of higher education of the latest generation.
For students of higher educational institutions studying in the field of Economics (master's degree, specialty), as well as teachers and postgraduates of universities, students of educational and methodological centers and practitioners of accounting and analytical services.