bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene co-expression changes underlying the functional connectomic alterations in Alzheimer’s disease
Authors: He Bing , Gorijala Priyanka , Xie Linhui , Cao Sha , Yan Jingwen 
Published: April 2022

Abstract
Background
There is growing evidence indicating that a number of functional connectivity networks are disrupted at each stage of the full clinical Alzheimer’s disease spectrum. Such differences are also detectable in cognitive normal (CN) carrying mutations of AD risk genes, suggesting a substantial relationship between genetics and AD-altered functional brain networks. However, direct genetic effect on functional connectivity networks has not been measured.

Methods
Leveraging existing AD functional connectivity studies collected in NeuroSynth, we performed a meta-analysis to identify two sets of brain regions: ones with altered functional connectivity in resting state network and ones without. Then with the brain-wide gene expression data in the Allen Human Brain Atlas, we applied a new biclustering method to identify a set of genes with differential co-expression patterns between these two set of brain regions.

Results
Differential co-expression analysis using biclustering method led to a subset of 38 genes which showed distinctive co-expression patterns between AD-related and non AD-related brain regions in default mode network. More specifically, we observed 4 sub-clusters with noticeable co-expression difference, where the difference in correlations is above 0.5 on average.

Conclusions
This work applies a new biclustering method to search for a subset of genes with altered co-expression patterns in AD-related default mode network regions. Compared with traditional differential expression analysis, differential co-expression analysis yielded many more significant hits with extra insights into the wiring mechanism between genes. Particularly, the differential co-expression pattern was observed between two sets of genes, suggesting potential upstream genetic regulators in AD development.
Metal ions/nucleotide coordinated nanoparticles comprehensively suppress tumor by synergizing ferroptosis with energy metabolism interference
Authors: Wang Yanqiu , Chen Jie , Lu Jianxiu , Xi Juqun , Xu Zhilong , Fan Lei , Dai Hua , Gao Lizeng 
Published: April 2022

Abstract
Background
Ferroptosis holds promise as a potential tumor therapy by programming cell death with a hallmark of reactive oxygen species (ROS)-induced lipid peroxidation. However, vigorous energy metabolism may assist tumors to resist oxidative damage and thus weaken the effects of ferroptosis in tumor treatment.

Results
Herein, a bifunctional antitumor platform was constructed via coordinated interactions between metal ions and nucleotides to synergistically activate ferroptosis and interrupt energy metabolism for tumor therapy. The designed nanoparticles were composed of Fe2+/small interfering RNA (siRNA) as the core and polydopamine as the cloak, which responded to the tumor microenvironment with structural dissociation, thereby permitting tumor-specific Fe2+ and siRNA release. The over-loaded Fe2+ ions in the tumor cells then triggered ferroptosis, with hallmarks of lipid peroxidation and cellular glutathione peroxidase 4 (GPX4) down-regulation. Simultaneously, the released siRNA targeted and down-regulated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in the tumor to inhibit glycolytic pathway, which interfered with tumor energy metabolism and enhanced Fe2+-induced ferroptosis to kill tumor cells.

Conclusions
This study presents a concise fabrication of a metal ion/nucleotide-based platform to integrate ferroptosis and energy metabolism intervention in one vehicle, thereby providing a promising combination modality for anticancer therapy.

Graphical Abstract
Association between quality of life and mental stress-induced myocardial ischaemia in high-risk patients after coronary revascularization
Authors: Nan Nan , Dong Wei , Gao Bingyu , Cui Feihuan , Chang Zhi , Jiao Jian , Zuo Huijuan , Mi Hongzhi , Song Xiantao , Lyu Shuzheng , Zhang Hongjia 
Published: April 2022

Abstract
Objective
We sought to determine the association between mental stress-induced myocardial ischaemia (MSIMI) and quality of life (QoL) in patients with coronary artery disease (CAD) after coronary revascularization.

Methods
This cohort study involved patients with high-risk MSIMI who received coronary revascularization between Dec 2018 and Dec 2019. Patients who screened positive for depression/anxiety were enrolled in this study. Mental stress was induced by the Stroop Colour and Word Test 1 month after coronary revascularization. All participants underwent single photon emission computed tomography (SPECT) scans at rest and under mental stress. MSIMI was defined as the presence of four abnormal SPECT phenomena. QoL was assessed using the Seattle Angina Questionnaire (SAQ) prior to treatment and 1 month after coronary revascularization.

Results
Of the 1845 consecutive patients who received coronary revascularization, 590 (31.9%) had depression/anxiety, and 205 agreed to accept the mental stress test. During the average observation period of 33 days, 105 (51.2%) patients exhibited MSIMI. All SAQ subscales showed significant improvement, except for QoL, in the MSIMI group. The QoL score was lower (− 0.2 ± 32.7 vs. 13.1 ± 29.9, P = 0.005), and the proportion of deterioration in QoL was higher (50.5% vs. 31.9%, P = 0.010) in the MSIMI group than in the non-MSIMI group. Those with a deterioration in QoL had approximately twice the rate of MSIMI than those with an improvement in QoL (unadjusted OR: 2.019, 95% CI 1.122–3.634, P = 0.026; adjusted OR: 1.968, 95% CI 1.083–3.578, P = 0.017).

Conclusion
Among patients with CAD who received coronary revascularization and had depression/anxiety, deterioration in QoL increased the likelihood of MSIMI. Hence, our results indicate that deterioration in QoL is a predictor of MSIMI.
Trail Registration ChiCTR2200055792, retrospectively registered, 2022.1.20, www.medresman.org.cn
A seven-autophagy-related gene signature for predicting the prognosis of differentiated thyroid carcinoma
Authors: Li Chengxin , Yuan Qianqian , Xu Gaoran , Yang Qian , Hou Jinxuan , Zheng Lewei , Wu Gaosong 
Published: April 2022

Abstract
Background
Numerous studies have implicated autophagy in the pathogenesis of thyroid carcinoma. This investigation aimed to establish an autophagy-related gene model and nomogram that can help predict the overall survival (OS) of patients with differentiated thyroid carcinoma (DTHCA).

Methods
Clinical characteristics and RNA-seq expression data from TCGA (The Cancer Genome Atlas) were used in the study. We also downloaded autophagy-related genes (ARGs) from the Gene Set Enrichment Analysis website and the Human Autophagy Database. First, we assigned patients into training and testing groups. R software was applied to identify differentially expressed ARGs for further construction of a protein-protein interaction (PPI) network for gene functional analyses. A risk score-based prognostic risk model was subsequently developed using univariate Cox regression and LASSO-penalized Cox regression analyses. The model’s performance was verified using Kaplan-Meier (KM) survival analysis and ROC curve. Finally, a nomogram was constructed for clinical application in evaluating the patients with DTHCA. Finally, a 7-gene prognostic risk model was developed based on gene set enrichment analysis.

Results
Overall, we identified 54 differentially expressed ARGs in patients with DTHCA. A new gene risk model based on 7-ARGs (CDKN2A, FGF7, CTSB, HAP1, DAPK2, DNAJB1, and ITPR1) was developed in the training group and validated in the testing group. The predictive accuracy of the model was reflected by the area under the ROC curve (AUC) values. Univariate and multivariate Cox regression analysis indicated that the model could independently predict the prognosis of patients with THCA. The constrained nomogram derived from the risk score and age also showed high prediction accuracy.

Conclusions
Here, we developed a 7-ARG prognostic risk model and nomogram for differentiated thyroid carcinoma patients that can guide clinical decisions and individualized therapy.
Significance of fibulin-3 expression in bladder cancer: a tissue microarray-based immunohistochemical study
Authors: Al Khader Ali , Fararjeh Abdul Fattah S. , Kaddumi Ezidin G. , Al-Saghbini Mohamad 
Published: April 2022

Abstract
Background
Predicting the behavior of bladder cancer by easy noninvasive methods and with less cost is needed. Fibulin-3 (EFEMP1), a glycoprotein of the extracellular matrix that is encoded by the gene EFEMP1, has been nominated as one of the potential mediators of muscle invasion in bladder cancer.

Methods
In this tissue microarray-based immunohistochemical study, fibulin-3 level of expression was evaluated using a semiquantitative scoring system and was correlated with patient’s age and sex and tumor grade and stage.

Results
A total of 160 urothelial carcinoma cases were analyzed. The age of the patients ranged from 25 to 91 years (mean, 60.15; SD, 11.60). Fibulin-3 was significantly associated with muscle invasion and overall tumor stage (p = 0.033 and 0.02, respectively). Fibulin-3 expression was nonsignificantly associated with tumor grade (p = 0.092)

Conclusions
We found that the expression of fibulin-3 is significantly associated with muscle invasion in urinary bladder urothelial carcinoma. However, the prognostic role of fibulin-3 needs further investigations.
Increased testicular insulin-like growth factor 1 is associated with gonadal activation by recombinant growth hormone in immature rats
Authors: Xu Yang , Han Chang Yong , Park Mi Jung , Gye Myung Chan 
Published: April 2022

AbstractBackgroundIn children, recombinant human growth hormone (rhGH) therapy for treatment of short stature has raised concerns of the early onset of puberty. Puberty is initiated by the activation of the hypothalamus-pituitary-gonad axis. Insulin-like growth factor-1 (IGF1) has been known to mediate physiologic effects of GH. To understand the mechanism of precocious sexual maturation following prepubertal GH therapy, the effects of rhGH on the hypothalamus-pituitary-gonad axis were examined in the immature male rats.MethodsImmature male rats were given by daily injection of rhGH (1 or 2 IU/kg) from postnatal day (PND) 21 to PND 23 or 30. The effects of rhGH on kisspeptin-GnRH-LH system in the hypothalamus-pituitary axis, systemic and testicular IGF1, spermatogenesis, steroidogenesis, and circulating testosterone levels were examined. The effects of rhGH on the IGF1 expression and steroidogenesis were examined in progenitor LCsin vitro.ResultsTesticular steroidogenic pathway and spermatogenesis marker mRNA levels, number and size of 17β-hydroxysteroid dehydrogenase (+) LCs, and blood testosterone levels of rhGH rats were significantly higher than those of controls on PNDs 24 and 31. HypothalamicKiss1andGnrh1mRNA of rhGH rats were significantly higher than those of controls on PND 24, indicating early activation of hypothalamic kisspeptin-GnRH neurons by rhGH. HypothalamicIgf1mRNA levels of rhGH rats were significantly higher than those of controls on PND 24 but significantly lower than those of controls on PND 31. TesticularIgf1mRNA levels were significantly higher in rhGH rats than in the controls on PNDs 24 and 31 whereas circulating IGF1 levels were not. In progenitor LCs, rhGH significantly increasedIgf1and steroidogenic pathway mRNA levels and testosterone production.ConclusionsLocal increases in testicular IGF1 might be an important mediator of gonadal maturation via activation of LCs steroidogenesis in immature rats given rhGH.
Practitioners’ perspectives on family-based intervention for illicit drug-using adolescents in Taiwan: a qualitative study
Authors: Huang Lanying 
Published: April 2022

Abstract
Background
Drug-related psychiatric comorbidity or death among adolescents has grown to become a public health threat in Taiwan. In an atmosphere of abstinence, few alternatives or rehabilitative options for troubled young people have caused many juveniles to be driven away from home and placed in closed institutions. The intersectionality of illegal substance use, deviant behaviours, and criminal offences among adjudicated adolescents is a challenge for the development of adolescent users’ harm reduction strategies. In addition, the relationships among the adolescents, their families, and practitioners might be undermined by coercive and mandatory court measures. As developing a harm reduction approach includes minimizing the negative effects on not only adolescents and also their families, this study aims to explore Taiwanese practitioners’ perspectives of family-based programmes for drug-using adolescents.

Methods
This study adopted a qualitative approach. Through face-to-face interviews and a focus group, accounts were collected from 28 key informants working in youth delinquency. The interviews were transcribed for analysis using qualitative analysis software, namely NVivo10.

Results
Practitioners tend to refer to an “adolescent-centred model” when describing their work with drug-using young people. From the frontline practitioners’ descriptions, the families of those youth needing treatment services are often vulnerable and disadvantaged. These families are seldom onboard because of low readiness and scarce resources. Although a legal framework is in place, resources, workforce, and programmes to engage and involve parents in the intervention are lacking. Despite the obstacles, practitioners have utilized a variety of strategies to obtain limited success, such as parent meetings, resources referrals, parent counselling, court support, voluntary parenting courses, illicit substance information sharing, and home visits. Practitioners also pointed out that therapeutic interventions are more effective than coercive or mandatory interventions for adolescents and also for their families.

Conclusions
Since most practitioners have an adolescent-centred work principle, their work with parents falls into professional-centred or family-allied work models. It is therefore suggested that resources be reallocated to involve parent counselling and intense treatment instead of mandatory parental education.
Semi-prone thoracoscopic esophagectomy for esophageal carcinoma with aberrant right subclavian artery and non-recurrent inferior laryngeal nerve
Authors: Koyama Kazunori , Watanabe Toru , Kato Hideaki , Kawaguchi Masahiko 
Published: April 2022

Abstract
Background
Aberrant right subclavian artery (ARSA) accompanied by non-recurrent inferior laryngeal nerve (NRILN) is a rare anomaly. In cases of thoracic esophageal carcinoma associated with ARSA and NRILN, surgeons must take extra care not to injury these vessels and nerves. We believe semi-prone thoracoscopic esophagectomy to be a surgical approach that can safely deal with such an anomaly.

Case presentation
A 70-year-old man complained of feelings of chest constriction. Endoscopic examination revealed an esophageal tumor and computed tomography showed an ARSA. We performed semi-prone thoracoscopic esophagectomy for case with ARSA and NRILN. We identified these anomalies during esophagectomy, and we could complete surgery without injury these vessels and nerves. The patient had an uneventful recovery and discharged 22 days after surgery.

Conclusions
Semi-prone thoracoscopic esophagectomy for esophageal carcinoma can be performed safely with a wide operative field, and is an excellent procedure for dissecting esophageal carcinoma in patients with ARSA and NRILN.
Trauma-focused treatments for refugee children: study protocol for a randomized controlled trial of the effectiveness of KIDNET versus EMDR therapy versus a waitlist control group (KIEM)
Authors: Velu Merel E. , Martens Irene , Shahab Mona , de Roos Carlijn , Jongedijk Ruud A. , Schok Michaela , Mooren T. 
Published: April 2022

Abstract
Background
Prevalence of posttraumatic stress disorder (PTSD) in refugees is reportedly higher in comparison to the general population. Refugee children specifically are often coping with trauma and loss and are at risk for mental health difficulties. With staggering numbers of people seeking refuge around the world and 50% being 18 years or younger, research examining the effects of trauma-focused therapies for refugee children with PTSD is highly needed. Both Eye Movement Desensitization and Reprocessing (EMDR) therapy and the child version of Narrative Exposure Therapy (KIDNET) have been used for refugees, although these treatment methods have not been systematically compared. The aim of the current study is to investigate the effectiveness of EMDR and KIDNET, compared to a waitlist control group and with each other, offered to refugee children.

Methods
A randomized controlled three-arm trial has been designed. The primary outcome is PTSD diagnosis and symptom severity assessed with the Clinician-Administered PTSD Scale for Children DSM5 (CAPS-CA-5) at baseline (T1), 1 month post-treatment, or after 8 weeks of waiting (T2) and 3 months follow-up (T3). Additionally, instruments to assess posttraumatic stress symptoms, behavioral and emotional problems, and quality of life perception in children aged 8–18 are conducted at T1, T2, and T3.

Discussion
This is the first RCT that examines the effectiveness of EMDR and KIDNET in refugee children aged 8–18 years specifically, compared to a waitlist control group intended to reduce PTSD diagnosis and severity of posttraumatic stress symptoms and comorbid complaints in a growing and challenging population.

Trial registration
Dutch Trial Register NL40769. Retrospectively registered on June 16, 2021.
An adaptive design to screen, treat, and retain people with opioid use disorders who use methamphetamine in methadone clinics (STAR-OM): study protocol of a clinical trial
Authors: Giang Le Minh , Trang Nguyen Thu , Diep Nguyen Bich , Thuy Dao Thi Dieu , Thuy Dinh Thanh , Hoe Han Dinh , Van Hoang Thi Hai , Truc Thai Thanh , Nguyen Hoa H. , Lai Nguyen Ly , Linh Pham Thi Dan , Vi Vu Thi Tuong , Reback Cathy J. , Leibowitz Arleen , Li Li , Lin Chunqing , Li Michael , Do Van Dung  , Shoptaw Steve 
Published: April 2022

Abstract
Background
Methamphetamine use could jeopardize the current efforts to address opioid use disorder and HIV infection. Evidence-based behavioral interventions (EBI) are effective in reducing methamphetamine use. However, evidence on optimal combinations of EBI is limited. This protocol presents a type-1 effectiveness-implementation hybrid design to evaluate the effectiveness, cost-effectiveness of adaptive methamphetamine use interventions, and their implementation barriers in Vietnam.

Method
Design: Participants will be first randomized into two frontline interventions for 12 weeks. They will then be placed or randomized to three adaptive strategies for another 12 weeks. An economic evaluation and an ethnographic evaluation will be conducted alongside the interventions.
Participants: We will recruit 600 participants in 20 methadone clinics. Eligibility criteria: (1) age 16+; (2) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores ≥ 10 for methamphetamine use or confirmed methamphetamine use with urine drug screening; (3) willing to provide three pieces of contact information; and (4) having a cell phone.
Outcomes: Outcomes are measured at 13, 26, and 49 weeks and throughout the interventions. Primary outcomes include the (1) increase in HIV viral suppression, (2) reduction in HIV risk behaviors, and (3) reduction in methamphetamine use.
COVID-19 response: We developed a response plan for interruptions caused by COVID-19 lockdowns to ensure data quality and intervention fidelity.

Discussion
This study will provide important evidence for scale-up of EBIs for methamphetamine use among methadone patients in limited-resource settings. As the EBIs will be delivered by methadone providers, they can be readily implemented if the trial demonstrates effectiveness and cost-effectiveness.

Trial registration
ClinicalTrials.gov NCT04706624. Registered on 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624
The effect of a social network-based cognitive behavioral therapy intervention on the severity of premenstrual syndrome symptoms: a protocol of a randomized clinical trial study
Authors: Alimoradi Zainab , Rajabalipour Somayeh , Rahmani Khaled , Pakpour Amir H. 
Published: April 2022

Abstract
Background
Premenstrual syndrome (PMS) is one of the most widespread menstrual disorders in women of reproductive age. This recurrent syndrome is a combination of physically, mentally, or behaviorally disturbing changes occurring during the secretory phase of the menstrual cycle. The aim of this study is to determine the effect of a cognitive-behavioral therapy-based educational intervention using social networks on PMS in female health center employees in Rudbar, Iran.

Methods/design
A randomized superiority controlled trial will be conducted involving 140 female employees of health centers affiliated with the Guilan University of Medical Sciences, Rudbar. The study involves a block size of 4 and 6 in a randomly varied order, 140 women who meet all the inclusion criteria will be randomly and equally divided into 2 groups: the intervention and the control groups. Those in the former group will receive a cognitive-behavioral therapy-based treatment for eight consecutive weeks on the social network platform WhatsApp; however, those in the control group will not be offered any treatment except usual care practices (unprotocolized usual care). The study’s primary outcome is the severity of PMS symptoms, and the secondary outcomes include general self-efficacy, work-related quality of life, the impact of PMS on daily life, coping with the symptoms, and experiencing anxiety and depression at the beginning of the study to identify people with PMS. A daily record of the symptoms will be completed for two consecutive months by all female employees aged 20–45 years who wish to participate in the study. According to the initial screening, those with moderate to severe PMS will be included. We will use the MLwin software for the analyses. All questionnaires will be completed by both groups immediately and 8 weeks after the termination of the treatment. The data will be analyzed using linear mixed-effects modeling with random intercepts and slopes.

Discussion
It is anticipated that the findings of the present study may demonstrate the effectiveness of the cognitive behavioral therapy intervention on the severity of PMS symptoms that could guide healthcare providers in opting for suitable treatment alternatives for the syndrome.

Ethics and dissemination
The research proposal is approved by the Human Ethics Committee of Qazvin University of Medical Sciences (IR.QUMS.REC.1399.252). The results of this intervention trial will be submitted for publication in a peer-reviewed research journal.

Trial registration
Iranian Registry of Clinical Trials IRCT20180218038789N4. Registered prospectively on October 28, 2020