bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBreast 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

Abstract
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

Abstract
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

Abstract
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

AbstractItch 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

Abstract
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

AbstractIn 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

Abstract
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

Abstract
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

AbstractBackgroundSoil-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.MethodsDuring 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.ResultsThe 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).ConclusionsThis 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