bluuebunny/crossref_metadata_2025_split huggingface dataset:
N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma
Authors: Chen Yuanlei , Lu Zeyi , Qi Chao , Yu Chenhao , Li Yang , Huan Wang , Wang Ruyue , Luo Wenqin , Shen Danyang , Ding Lifeng , Ren Liangliang , Xie Haiyun , Xue Dingwei , Wang Mingchao , Ni Kangxin , Xia Liqun , Qian Jun , Li Gonghui 
Published: May 2022

Abstract
Background
Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear.

Methods
RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis.

Results
We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment.

Conclusions
Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.
Hsa-miR-3178/RhoB/PI3K/Akt, a novel signaling pathway regulates ABC transporters to reverse gemcitabine resistance in pancreatic cancer
Authors: Gu Jianyou , Huang Wenjie , Wang Xianxing , Zhang Junfeng , Tao Tian , Zheng Yao , Liu Songsong , Yang Jiali , Chen Zhe-Sheng , Cai Chao-Yun , Li Jinsui , Wang Huaizhi , Fan Yingfang 
Published: May 2022

Abstract
Background
Although gemcitabine has been considered as the first-line drug for advanced pancreatic cancer (PC), development of resistance to gemcitabine severely limits the effectiveness of this chemotherapy, and the underlying mechanism of gemcitabine resistance remains unclear. Various factors, such as ATP binding cassette (ABC) transporters, microRNAs and their downstream signaling pathways are included in chemoresistance to gemcitabine. This study investigated the potential mechanisms of microRNAs and ABC transporters related signaling pathways for PC resistance to gemcitabine both in vivo and in vitro.

Methods
Immunohistochemistry and Western blotting were applied to detect the expression of ABC transporters. Molecular docking analysis was performed to explore whether gemcitabine interacted with ABC transporters. Gain-of-function and loss-of-function analyses were performed to investigate the functions of hsa-miR-3178 in vitro and in vivo. Bioinformatics analysis, Western blotting and dual-luciferase reporter assay were used to confirm the downstream regulatory mechanisms of hsa-miR-3178.

Results
We found that P-gp, BCRP and MRP1 were highly expressed in gemcitabine-resistant PC tissues and cells. Molecular docking analysis revealed that gemcitabine can bind to the ABC transporters. Hsa-miR-3178 was upregulated in gemcitabine resistance PANC-1 cells as compared to its parental PANC-1 cells. Moreover, we found that hsa-miR-3178 promoted gemcitabine resistance in PC cells. These results were also verified by animal experiments. RhoB was down-regulated in gemcitabine-resistant PC cells and it was a downstream target of hsa-miR-3178. Kaplan–Meier survival curve showed that lower RhoB expression was significantly associated with poor overall survival in PC patients. Rescue assays demonstrated that RhoB could reverse hsa-miR-3178-mediated gemcitabine resistance. Interestingly, hsa-miR-3178 promoted gemcitabine resistance in PC by activating the PI3K/Akt pathway-mediated upregulation of ABC transporters.

Conclusions
Our results indicate that hsa-miR-3178 promotes gemcitabine resistance via RhoB/PI3K/Akt signaling pathway-mediated upregulation of ABC transporters. These findings suggest that hsa-miR-3178 could be a novel therapeutic target for overcoming gemcitabine resistance in PC.
FMRP ligand circZNF609 destabilizes RAC1 mRNA to reduce metastasis in acral melanoma and cutaneous melanoma
Authors: Shang Qingfeng , Du Haizhen , Wu Xiaowen , Guo Qian , Zhang Fenghao , Gong Ziqi , Jiao Tao , Guo Jun , Kong Yan 
Published: May 2022

Abstract
Background
Melanoma is a type of malignant tumor with high aggressiveness and poor prognosis. At present, metastasis of melanoma is still an important cause of death in melanoma patients. However, the potential functions and molecular mechanisms of most circular RNAs (circRNAs) in melanoma metastasis remain unknown.

Methods
circRNAs dysregulated in melanoma cell subgroups with different metastatic abilities according to a screening model based on repeated Transwell assays were identified with a circRNA array. The expression and prognostic significance of circZNF609 in skin cutaneous melanoma and acral melanoma cells and tissues were determined by qRT–PCR, nucleoplasmic separation assays and fluorescence in situ hybridization. In vitro wound healing, Transwell and 3D invasion assays were used to analyse melanoma cell metastasis ability. Tail vein injection and intrasplenic injection were used to study in vivo lung metastasis and liver metastasis, respectively. The mechanism of circZNF609 was further evaluated via RNA immunoprecipitation, RNA pull-down, silver staining, and immunofluorescence colocalization assays.

Results
circZNF609 was stably expressed at low levels in melanoma tissues and cells and was negatively correlated with Breslow depth, clinical stage and prognosis of melanoma patients. circZNF609 inhibited metastasis of acral and cutaneous melanoma in vivo and in vitro. Mechanistically, circZNF609 promoted the binding of FMRP protein and RAC1 mRNA, thereby enhancing the inhibitory effect of FMRP protein on the stability of RAC1 mRNA and ultimately inhibiting melanoma metastasis.

Conclusions
Our findings revealed that circZNF609 plays a vital role in the metastasis of acral and cutaneous melanoma through the circRNF609-FMRP-RAC1 axis and indicated that circZNF609 regulates the stability of RAC1 mRNA by combining with FMRP, which might provide insight into melanoma pathogenesis and a new potential target for treatment of melanoma.
Factors associated with age of diagnosis of autism spectrum disorder among children in Saudi Arabia: new insights from a cross-sectional study
Authors: Alnemary Fahad M. , Alnemary Faisal M. , Simon-Cereijido Gabriela , Aldhalaan Hesham M. , Hernandez Anthony , Alyahya Ahmed , Alenezi Shuliweeh 
Published: May 2022

Abstract
Objectives
Research examining the age of diagnosis of autism spectrum disorder (ASD) and its influencing factors mostly originate from developed Western countries, providing little to no systematic information about the understanding and management of ASD in the rest of the world. The present exploratory study examined the influence of child and family characteristics on the age of ASD diagnosis in Saudi Arabia.

Results
The median age at diagnosis was 3.0 years and was associated with some child and family characteristics. A 1 year increase in child’s age was associated with a 0.1 year increase in age of diagnosis (95% CI 0.05, 0.12). Children who did not respond to their name were diagnosed 0.3 years earlier than other children (95% CI − 0.60, − 0.05), and engaging in challenging behavior was associated with a 0.5 year increase in age of diagnosis (95% CI 0.20, 0.81). A lack of comorbidity was associated with a 0.6 year increase in the age of diagnosis compared to the diagnosis age of children with comorbidity (95% CI 0.13, 1.01). Finally, those residing outside of Saudi Arabia were diagnosed with ASD 0.9 years earlier than those residing in Saudi Arabia (95% CI − 0.171, − 0.11).
Face image synthesis from facial parts
Authors: Sun Qiushi , Guo Jingtao , Liu Yi 
Published: May 2022

AbstractRecently, inspired by the growing power of deep convolutional neural networks (CNNs) and generative adversarial networks (GANs), facial image editing has received increasing attention and has produced a series of wide-ranging applications. In this paper, we propose a new and effective approach to a challenging task: synthesizing face images based on key facial parts. The proposed approach is a novel deep generative network that can automatically align facial parts with the precise positions in a face image and then output an entire facial image conditioned on the well-aligned parts. Specifically, three loss functions are introduced in this approach, which are the key to making the synthesized realistic facial image: a reconstruction loss to generate image content in an unknown region, a perceptual loss to enhance the network's ability to model high-level semantic structures and an adversarial loss to ensure that the synthesized images are visually realistic. In this approach, the three components cooperate well to form an effective framework for parts-based high-quality facial image synthesis. Finally, extensive experiments demonstrate the superior performance of this method to existing solutions.
Effect of High-intensity Training and Probiotics on Gut Microbiota Diversity in Competitive Swimmers: Randomized Controlled Trial
Authors: Bielik Viktor , Hric Ivan , Ugrayová Simona , Kubáňová Libuša , Putala Matúš , Grznár Ľuboš , Penesová Adela , Havranová Andrea , Šardzíková Sára , Grendar Marián , Baranovičová Eva , Šoltys Katarína , Kolisek Martin 
Published: May 2022

Abstract
Background
Physical exercise has favorable effects on the structure of gut microbiota and metabolite production in sedentary subjects. However, little is known whether adjustments in an athletic program impact overall changes of gut microbiome in high-level athletes. We therefore characterized fecal microbiota and serum metabolites in response to a 7-week, high-intensity training program and consumption of probiotic Bryndza cheese.

Methods
Fecal and blood samples and training logs were collected from young competitive male (n = 17) and female (n = 7) swimmers. Fecal microbiota were categorized using specific primers targeting the V1–V3 region of 16S rDNA, and serum metabolites were characterized by NMR-spectroscopic analysis and by multivariate statistical analysis, Spearman rank correlations, and Random Forest models.

Results
We found higher α-diversity, represented by the Shannon index value (HITB-pre 5.9 [± 0.4]; HITB-post 6.4 [± 0.4], p = 0.007), (HIT-pre 5.5 [± 0.6]; HIT-post 5.9 [± 0.6], p = 0.015), after the end of the training program in both groups independently of Bryndza cheese consumption. However, Lactococcus spp. increased in both groups, with a higher effect in the Bryndza cheese consumers (HITB-pre 0.0021 [± 0.0055]; HITB-post 0.0268 [± 0.0542], p = 0.008), (HIT-pre 0.0014 [± 0.0036]; HIT-post 0.0068 [± 0.0095], p = 0.046). Concomitant with the increase of high-intensity exercise and the resulting increase of anaerobic metabolism proportion, pyruvate (p[HITB] = 0.003; p[HIT] = 0.000) and lactate (p[HITB] = 0.000; p[HIT] = 0.030) increased, whereas acetate (p[HITB] = 0.000; p[HIT] = 0.002) and butyrate (p[HITB] = 0.091; p[HIT] = 0.019) significantly decreased.

Conclusions
Together, these data demonstrate a significant effect of high-intensity training (HIT) on both gut microbiota composition and serum energy metabolites. Thus, the combination of intensive athletic training with the use of natural probiotics is beneficial because of the increase in the relative abundance of lactic acid bacteria.
Systems Analysis and Improvement Approach to optimize the pediatric and adolescent HIV Cascade (SAIA-PEDS): a pilot study
Authors: Wagner Anjuli D. , Augusto Orvalho , Njuguna Irene N. , Gaitho Douglas , Mburu Nancy , Oluoch Geoffrey , Carimo Naziat , Mwaura Peter , Cherutich Peter , Oyiengo Laura , Gimbel Sarah , John-Stewart Grace C. , Nduati Ruth , Sherr Kenneth 
Published: May 2022

Abstract
Introduction
Children and adolescents lag behind adults in achieving UNAIDS 95-95-95 targets for HIV testing, treatment, and viral suppression. The Systems Analysis and Improvement Approach (SAIA) is a multi-component implementation strategy previously shown to improve the HIV care cascade for pregnant women and infants. SAIA merits adaptation and testing to reduce gaps in the pediatric and adolescent HIV cascade.

Methods
We adapted the SAIA strategy components to be applicable to the pediatric and adolescent HIV care cascade (SAIA-PEDS) in Nairobi and western Kenya. We tested whether this SAIA-PEDS strategy improved HIV testing, linkage to care, antiretroviral treatment (ART), viral load (VL) testing, and viral load suppression for children and adolescents ages 0–24 years at 5 facilities. We conducted a pre-post analysis with 6 months pre- and 6 months post-implementation strategy (coupled with an interrupted time series sensitivity analysis) using abstracted routine program data to determine changes attributable to SAIA-PEDS.

Results
Baseline levels of HIV testing and care cascade indicators were heterogeneous between facilities. Per facility, the monthly average number of children/adolescents attending outpatient and inpatient services eligible for HIV testing was 842; on average, 253 received HIV testing services, 6 tested positive, 6 were linked to care, and 5 initiated ART. Among those on treatment at the facility, an average of 15 had a VL sample taken and 13 had suppressed VL results returned.
Following the SAIA-PEDS training and mentorship, there was no substantial or significant change in the ratio of HIV testing (RR: 0.803 [95% CI: 0.420, 1.532]) and linkage to care (RR: 0.831 [95% CI: 0.546, 1.266]). The ratio of ART initiation increased substantially and trended towards significance (RR: 1.412 [95% CI: 0.999, 1.996]). There were significant and substantial improvements in the ratio of VL tests ordered (RR: 1.939 [95% CI: 1.230, 3.055]) but no substantial or significant change in the ratio of VL results suppressed (RR: 0.851 [95% CI: 0.554, 1.306]).

Conclusions
The piloted SAIA-PEDS implementation strategy was associated with increases in health system performance for indicators later in the HIV care cascade, but not for HIV testing and treatment indicators. This strategy merits further rigorous testing for effectiveness and sustainment.
Barbed suture pharyngoplasty in velopharyngeal complete concentric collapse: a multicentric study
Authors: Castillo-Farias Felipe , Carrasco-Llatas Marina , Bosco Gabriela , Rinaldi Vittorio , Baptista-Jardín Peter Michael , Cammaroto Giovanni , Alkan Uri , Muñoz-Fernandez Noelia , Rosel Pablo , Bachelet Cristian , Casale Manuele , Moffa Antonio , Plaza-Mayor Guillermo , Perez-Martin Nuria , Vicini Claudio 
Published: May 2022

Abstract
Background
Studies have shown that complete concentric circular collapse (CCC) at the velum is a frequent finding in drug-induced sleep endoscopy, implying a worse prognosis for surgical outcomes in the treatment of obstructive sleep apnea syndrome (OSAS). Our group evaluated the results of pharyngoplasties with barbed sutures for this indication. We selected 48 patients with OSAS and CCC who underwent pharyngoplasty with barbed sutures in 8 tertiary centers. The outcome results were measured by polygraphy or polysomnography and Epworth Symptoms Scale (ESS) at least 6 months after surgery.

Results
Apnea Hypopnea Index (AHI) improved from 34.9/h [21.2] to 12.7/h [10.6]. The success rate according to Sher’s criteria was 86.7%, the cure rate was 23.9%, and an AHI < 10 occurred in 42.2% of the cases. The oxygen desaturation index improved from 32.5/h [29.9] to 12.5/h SD [11.6], and the ESS improved from 10.2 [5.2] to 6 [3.5].

Conclusions
Pharyngoplasty with barbed sutures seems to be a good alternative for patients with OSAS and CCC findings in drug-induced sleep endoscopy.
Thrombocytopenic patients with hematological malignancy who underwent fiberoptic bronchoscopy are they really under a significant hemorrhagic risk?
Authors: Yıldırım Fatih , Özkalemkaş Fahir , Ursavaş Ahmet 
Published: May 2022

Abstract
Background
Fiberoptic bronchoscopy (FOB) is a very important procedure in hematology clinics. Clinicians often worry about thrombocytopenia before performing FOB because hemorrhagic complications may occur during and after FOB. We have planned a retrospective study about hemorrhagic complications in thrombocytopenic patients who underwent FOB and treated for hematological malignancy. In this study, we have analyzed hemorrhagic complications, which are related to thrombocytopenia, in 114 adult patients who have hematologic malignancy and underwent FOB between January 1, 2005 and October 20, 2015. The platelet counts of all the patients were below 100 × 109/L.

Results
The complications related to FOB were observed in 4 (3.5%) out of 114 patient. Three out of 4 the complications were related to hemorrhage. One out of these 3 patients who occured hemorrhage was in “no bleeding group” according to BTS classification. The other 1 out of these 3 patients was in “mild bleeding” group. No bleeding was observed during FOB in the third patient. Hemoptysis was observed after FOB in the third patient, it was not required replacement and hemoptysis regressed spontaneously.
In this study, we categorized all the patients into three groups. The first group was comprised of 32 patients whose platelet counts were between 0 and 30 × 109/L. The second group was comprised of 47 patients whose platelets counts were between 30 and 50 × 109/L and lastly, the third group was comprised of 35 patients whose platelets counts were between 50 and 100 × 109/L. When we compared the groups to each other, there was no significant difference between these three groups in regards to occurrence of hemorrhagic complications. We observed that there was no significant relationship between thrombocytopenia level and risk of hemorrhagic complications in thrombocytopenic patients who underwent FOB.

Conclusions
In conclusion, this study demonstrated that FOB is safe procedures in thrombocytopenic patients if it is performed in multidisciplinary centers by experienced pulmonologists.
Slow and Steady Wins the Race: 25 Years Developing the GLP-1 Receptor as an Effective Target for Weight Loss
Authors: Kumar Nitya , D’Alessio David A 
Published: May 2022

Abstract
Recent evidence from clinical trials supports the efficacy and tolerability of glucagon-like peptide 1 (GLP-1) receptor agonists as useful agents for weight loss. Although originally developed as glucose lowering agents for people with type 2 diabetes, progress in research over the last 3 decades has demonstrated that GLP-1 receptor agonists act in the central nervous system to reduce food intake. This minireview summarizes key aspects of GLP-1 biology and the clinical studies supporting the utility of the GLP-1 receptor signaling system as a therapeutic target for weight loss.
„A ci, którzy chcą się bogacić”. Analiza lingwistyczno-teologiczna 1 Tm 6,9.
Authors: Tomczyk Dominik Tomasz 
Published: May 2022

Autor artykułu przedstawia analizę lingwistyczno-teologiczną tekstu 1 Tm 6,9, który jest parenetycznym pouczeniem o możliwych niebezpieczeństwach czekających tych, którzy chcą się bogacić. Poprzestawanie na tym, co się już posiada w perspektywie życia wiecznego jest ważniejsze od pomnażania swoich majętności.W 1 Tm 6,9 wyodrębnić możemy dwa główne etapy niebezpieczeństw: „wpadanie” i „zatapianie”. W etapie „wpadania” można wyodrębnić trzy podetapy (próba, sidła, pragnienia), zaś w etapie „zatapiania” dwa podetapy (zguba, zatracenie). Niepohamowane pragnienie bogacenia się może w konsekwencji doprowadzić nawet do wiecznego potępienia.
ESSA CONSTRUÇÃO SOFREU MÓ MUDANÇA DE LÁ PRA CÁ: POSSÍVEL TRAJETÓRIA EVOLUTIVA DA CONSTRUÇÃO [MÓX]
Authors: Freitas Jr Roberto , Silva Érica Cristina , Barbosa Kleveland Cristian 
Published: May 2022

O artigo em tela apresenta o recorte de uma pesquisa de mestrado em desenvolvimento e discute a possível construcionalização da Construção de Informalidade e Intensificação [MóX], vulgo construção [MóX], no Português do Brasil. À luz da Linguística Funcional Centrada no Uso (GOLDBERG, 2006; CROFT, 2001; HILPERT, 2014; PEREK, 2015; BYBEE, 2008 e 2010; TRAUGOTT e TROUSDALE, 2013), tendo como aporte teórico a Gramática de Construções Baseada no Uso, o presente trabalho tem como objetivo mapear, analisar e descrever sincronicamente os contextos de uso de expressões como [Mó saudade], [Mó legal], [Mó relembrando], [Mó mal] no PB na tentativa de compreender como se deu esse possível processo de construcionalização. Sob a perspectiva construcional, algumas propriedades do pareamento forma e função serão observadas, visto serem esses os critérios que determinam e definem o novo nó na rede construcional. Para robustecer a ideia de que a construção [MóX] possa ser um exemplo de mudança, tal qual defendido pelo modelo de construcionalização, processos cognitivos de domínio geral como chunking e memória enriquecida serão abordados. Para situar o estudo e comprovar a criação desse novo nó, foi necessário remontar ao latim, ao galego-português e ao português do século XX e XXI, sendo também realizado um mapeamento de dados extraídos do Twitter. Os dados foram usados para analisar historicamente a evolução e transformação da construção.
Health system use among patients with mental health conditions in a community based sample in Toronto, Canada: A retrospective cohort study
Authors: Lazare Kimberly , Kalia Sumeet , Aliarzadeh Babak , Bernard Steven , Moineddin Rahim , Eisen David , Greiver Michelle , Kaplan David , Koczerginski David , Muraca Maria , Fung Wai Lun Alan , O’Neill Braden 
Published: May 2022

Objective
To identify hospital and primary care health service use among people with mental health conditions or addictions in an integrated primary-secondary care database in Toronto, Ontario.

Method
This was a retrospective cohort study of adults with mental health diagnoses using data from the Health Databank Collaborative (HDC), a primary care-hospital linked database in Toronto. Data were included up to March 31st 2019. Negative binomial and logistic regression were used to evaluate associations between health care utilization and various patient characteristics and mental health diagnoses.

Results
28,482 patients age 18 or older were included. The adjusted odds of at least one mental health diagnosis were higher among younger patients (18–30 years vs. 81+years aOR = 1.87; 95% CI:1.68–2.08) and among female patients (aOR = 1.35; 95% CI: 1.27–1.42). Patients with one or more mental health diagnoses had higher adjusted rates of hospital visits compared to those without any mental health diagnosis including addiction (aRR = 1.74, 95% CI: 1.58–1.91) and anxiety (aRR = 1.28, 95% CI: 1.23–1.32). 14.5% of patients with a psychiatric diagnosis were referred to the hospital for specialized psychiatric services, and 38% of patients referred were eventually seen in consultation. The median wait time from the date of referral to the date of consultation was 133 days.

Conclusions
In this community, individuals with mental health diagnoses accessed primary and hospital-based health care at greater rates than those without mental health diagnoses. Wait times for specialized psychiatric care were long and most patients who were referred did not have a consultation. Information about services for patients with mental health conditions can be used to plan and monitor more integrated care across sectors, and ultimately improve outcomes.