bluuebunny/crossref_metadata_2025_split huggingface dataset:
αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma
Authors: Gu Yongwei , Du Yue , Jiang Liangdi , Tang Xiaomeng , Li Aixue , Zhao Yunan , Lang Yitian , Liu Xiaoyan , Liu Jiyong 
Published: August 2022

Abstract
Background
Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potential of TP is plagued by its poor aqueous solubility, short half-life, and biotoxicity. Therefore, developing an ideal vehicle to efficiently load TP and achieving targeted delivery to melanoma is a prospective approach for making full use of its antitumor efficacy.

Results
We applied exosome (Exo) derived from human umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 157.34 ± 6.21 nm, with a high drug loading of 10.76 ± 1.21%. The in vitro antitumor results showed that the designed Exo delivery platform could be effectively taken up by targeted cells and performed significantly in antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via the caspase cascade and mitochondrial pathways and cell cycle alteration. Furthermore, the biodistribution and pharmacokinetics results demonstrated that cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended survival time with negligible systemic toxicity in tumor-bearing mice.

Conclusion
The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma.

Graphical Abstract
Mesoporous silica-coated silver nanoparticles as ciprofloxacin/siRNA carriers for accelerated infected wound healing
Authors: Liu Qiqi , Zhang Ying , Huang Jingkai , Xu Zhourui , Li Xiang , Yang Jingyu , Huang Haoqiang , Tang Shiqi , Chai Yujuan , Lin Jinbo , Yang Chengbin , Liu Jia , Lin Suxia 
Published: August 2022

AbstractThe colonization of bacterial pathogens is a major concern in wound infection and becoming a public health issue. Herein, a core–shell structured Ag@MSN (silver core embedded with mesoporous silica, AM)-based nanoplatform was elaborately fabricated to co-load ciprofloxacin (CFL) and tumor necrosis factor-α (TNF-α) small interfering RNA (siTNF-α) (AMPC@siTNF-α) for treating the bacterial-infected wound. The growth of bacterial pathogens was mostly inhibited by released silver ions (Ag+) and CFL from AMPC@siTNF-α. Meanwhile, the loaded siTNF-α was internalized by macrophage cells, which silenced the expression of TNF-α (a pro-inflammatory cytokine) in macrophage cells and accelerated the wound healing process by reducing inflammation response. In the in vivo wound model, theEscherichia coli (E. coli)-infected wound in mice almost completely disappeared after treatment with AMPC@siTNF-α, and no suppuration symptom was observed during the course of the treatment. Importantly, this nanoplatform had negligible side effects both in vitro and in vivo. Taken together, this study strongly demonstrates the promising potential of AMPC@siTNF-α as a synergistic therapeutic agent for clinical wound infections.Graphical Abstract
Pulmonary embolism in a patient with eltrombopag-treated aplastic anaemia and paroxysmal nocturnal haemoglobinuria clone during COVID-19 pneumonia
Authors: Bosi Alessandro , Barcellini Wilma , Fattizzo Bruno 
Published: August 2022

AbstractThrombosis in patients with thrombocytopenia has several risk factors, both disease-related and treatment-associated. Recently, COVID-19 infection was recognized as an additional risk factor, further complicating the delicate balance between thrombosis and bleeding in these patients. Here we describe the case of a patient with aplastic anaemia on eltrombopag who developed pulmonary embolism during COVID-19 pneumonia, despite receiving oral anticoagulation with edoxaban. Notably, he was also carrying a large paroxysmal nocturnal haemoglobinuria clone, although without evidence of haemolysis. The presented case recapitulates some of the open questions in thrombotic risk management of cytopenic patients, such as the management of thrombopoietin receptor agonists and the choice of anticoagulation in PNH, while also accounting for the additional thrombotic risk linked to COVID-19.
A retrospective study comparing definitive chemoradiotherapy vs. chemoradiotherapy followed by surgery in T4 esophageal squamous cell carcinoma patients who were downstaged after neochemoradiotherapy
Authors: Zhang Tian , Guo Zhoubo , Chen Xi , Dong Jie , Jiang Hongjing , Tang Peng , Wang Ping , Qian Dong , Zhang Wencheng , Pang Qingsong 
Published: August 2022

Abstract
Background
The outcome of patients with T4 esophageal squamous cell carcinoma (ESCC) is extremely poor. Two distinct therapeutic options are currently available for T4 esophageal cancers: neochemoradiotherapy followed by surgery (CRT-S) and definitive chemoradiotherapy (D-CRT). This study aimed to investigate the clinicopathologic characteristics of T4 ESCC in Chinese patients and compare the survival between the two therapeutic options.

Methods
We retrospectively analyzed 125 patients with clinically unresectable T4 ESCC in Tianjin Medical University Cancer Institute and Hospital from January 2010 to December 2020. Overall survival (OS), progression-free survival (PFS) and associated factors were analyzed.

Results
A total of 106 of 125 T4 ESCC patients were downstaged of the tumor by neoadjuvant CRT. Among 106 patients, 32 patients underwent CRT-S, and 74 patients underwent D-CRT. Patients in the CRT-S group had a higher OS (20.4 months vs. un-reached median OS, p = 0.037) and PFS (8.6 months vs. 21.0 months, p = 0.008) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor of PFS. After propensity score matching (PSM), 50 patients (CRT-S = 25; D-CRT = 25) were matched. Among these 50 patients, patients in the CRT-S group had a higher OS (15.6 months vs. un-reached median OS, p = 0.025) and PFS (7.2 months vs. 18.8 months, p = 0.026) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor for PFS.

Conclusion
We demonstrated that CRT-S was superior to D-CRT for T4 ESCC patients who were downstaged by neo-CRT with respect to longer OS and PFS. Randomized controlled trials involving large population samples are needed to define the standard treatment for T4 ESCC.
A rare case of posttraumatic aortic rupture, treated with an endovascular stent graft implantation and complicated with esophageal rupture
Authors: Kyuchukov Dimitar , Simeonov Peyo , Nachev Gencho , Alexieva Magdalena , Yankov Georgi 
Published: August 2022

Abstract
Background
Esophageal necrosis and perforation after thoracic endovascular aortic repair (TEVAR) for ruptured traumatic aortic aneurysm is extremely rare. It is difficult to manage, and patients rarely survive without treatment. Although, there is no certain consensus in relation with the optimal treatment we present a subsequent successful management of both life-threatening conditions.

Case presentation
A 52-year-old man experienced a blunt chest trauma after motor vehicle collision with mild symptoms of pain and fractured ribs. On the 12th day he had severe chest pain and computed tomography (CT) revealed a ruptured traumatic thoracic aortic aneurysm with massive mediastinal hematoma. An emergency thoracic endovascular aortic repair (TEVAR) was performed. Several days later the patient developed a fever. CT suspected a pneumomediastinum, a sign of esophageal rupture, but no confirmation from esophagography and esophagoscopy was achieved. Because of deteriorated septic condition, patient was referred for exploratory thoracotomy. The rupture was found and esophagectomy was performed, with an esophagostomy and gastrostomy to enable enteral nutrition. Almost one year after the esophagectomy, gastric conduit reconstruction through the retrosternal route was performed. The patient was still alive and symptom-free more than 1 year after the reconstruction and no infection of the stent graft was observed.

Conclusion
We successfully managed a rare case of esophageal necrosis after TEVAR for ruptured traumatic thoracic aortic aneurysm. It is essential to diagnose the esophageal necrosis at an early stage and provide appropriate treatment to increase survival.
Accuracy of a community mental health education and detection (CMED) tool for common mental disorders in KwaZulu-Natal, South Africa
Authors: Grant Merridy , Petersen Inge , Mthethwa Londiwe , Luvuno Zamasomi , Bhana Arvin 
Published: August 2022

Abstract
Background
Screening tools for mental health disorders improve detection at a primary health care (PHC) level. However, many people with mental health conditions do not seek care because of a lack of knowledge about mental health, stigma about mental illness and a lack of awareness of mental health services available at a PHC facility level. Interventions at a community level that raise awareness about mental health and improve detection of mental health conditions, are thus important in increasing demand and optimising the supply of available mental health services. This study sought to evaluate the accuracy of a Community Mental Health Education and Detection (CMED) Tool in identifying mental health conditions using pictorial vignettes.

Methods
Community Health Workers (CHWs) administered the CMED tool to 198 participants on routine visits to households. Consenting family members provided basic biographical information prior to the administration of the tool. To determine the accuracy of the CMED in identifying individuals in households with possible mental health disorders, we compared the number of individuals identified using the CMED vignettes to the validated Brief Mental Health (BMH) screening tool.

Results
The CMED performed at an acceptable level with an area under the curve (AUC) of 0.73 (95% CI 0.67–0.79), identifying 79% (sensitivity) of participants as having a possible mental health problem and 67% (specificity) of participants as not having a mental health problem. Overall, the CMED positively identified 55.2% of household members relative to 49.5% on the BMH.

Conclusion
The CMED is acceptable as a mental health screening tool for use by CHWs at a household level.
Development and pilot testing of a five item traumatic stress screener for use with adolescents in pediatric primary care
Authors: Ng Lauren C. , Oblath Rachel , Brigham Rebecca , Tai Ming Him , Coles Mandy 
Published: August 2022

Abstract
Background
Almost 80% of adolescents in the US have experienced a traumatic event, and approximately 7% have post-traumatic stress disorder. However, there is a lack of validated and feasible assessments for assessing traumatic stress symptoms in pediatric primary care, and traumatic stress symptoms are routinely unidentified. This study aimed to develop, pilot test, and assess the psychometric properties of the Adolescent Primary Care Traumatic Stress Screen (APCTSS), a five-item yes/no screener for post-traumatic stress symptoms in adolescents designed for use in pediatric primary care.

Methods
The APCTSS was developed by pediatricians, psychiatrists, psychologists, and social workers who all provide care to trauma-affected adolescent patients. The providers sought to create a developmentally appropriate tool that accurately reflected DSM-5 posttraumatic stress symptoms and that was feasible and acceptable for use in pediatric primary care. To develop the APCTSS, they combined and adapted the UCLA Post-traumatic Stress Disorder (PTSD) Reaction Index for DSM-5 with the adult Primary Care PTSD Screen for DSM-5. Next, 213 adolescent medicine patients were universally approached during routine clinic visits and 178 agreed to participate and were enrolled. The 178 patients were aged 13-22 (M=18.4, SD=2.3), 64.4% female; 62.1% Black or African-American, and 20.7% Hispanic/Latinx. Patients completed APCTSS, Patient Health Questionnaire for Adolescents (PHQ-A), and the Child PTSD Symptom Scale for DSM-5 Interview (CPSS-5-I), and 61 completed the Traumatic Events Screening Inventory for Children (TESI-C).

Results
56.7% reported a criterion A trauma, 30.1% met criteria for DSM-5 PTSD, 7.4% met criteria for subsyndromal PTSD symptoms, and 19.0% for post-event impairing symptoms. Validity and reliability testing indicated that the APCTSS was internally consistent, had good concurrent and discriminant validity, and demonstrated good sensitivity and specificity in identifying adolescents at high risk for post-trauma symptoms. Over half of patients (56.0%) who screened positive on the APCTSS (score ≥2) would not have been identified as having a mental health concern using the PHQ-A, including 60.8% of patients who had probable PTSD, subsyndromal PTSD, or post-event impairing symptoms.

Conclusions
Many youth with trauma-related mental health symptoms are unidentified in pediatric primary care, which is a missed opportunity for early identification and may contribute to a host of poor outcomes. The development of an effective and feasible traumatic stress screening tool for youth primary care may improve early intervention, and the health and well-being of trauma affected youth.
Towards school-based mental health programs in Nigeria: the immediate impact of a depression-literacy program among school-going adolescents and their teachers
Authors: Atilola Olayinka , Ayinde Olatunde , Obialo Felix-Kingsley , Adeyemo Sunday Oladotun , Adegbaju Dapo , Anthony Robert 
Published: August 2022

Abstract
Background
Depression-literacy, which is the foundational requirement for symptom recognition, positive attitude and help-seeking, is poor among adolescents in Nigeria. This study, therefore, aims to determine the impact of a school-based training program on depression-literacy among a cohort of high-school students and their teachers in South-West Nigeria.

Methods
An adapted version of the Break Free from Depression, a 4-module depression awareness curriculum for staff and students, was implemented among students and their teachers. Paired-sample T-test was used to assess the domain-specific (knowledge, attitude, and confidence) impact of the training by comparing the baseline and immediate (within the week of the training) post-scores.

Results
A total of 3098 students and 294 teachers from 21 schools across three states in South-West Nigeria successfully completed the training. There was a significant positive difference (p < 0.05), at post-test, in the knowledge, attitude, and confidence among the students. The same was observed among teachers except for attitude where positive change did not reach significant level (p = 0.06). When statistically significant, the calculated effect size (eta squared) was highest for knowledge (students: 0.07, p = 0.001; teachers: 0.08, p < 0.000) and least for attitude (students: 0.003, p = 0.002 teachers: 0.085, p = 0.06). Multiple regression analyses result showed that the level of pre-scores predicted the magnitude of change in all domains of depression-literacy (p < 0.05) after controlling for age, gender, and type of school among the students, but not for teachers.

Conclusions
School-based depression-literacy programs can lead to significant positive change in knowledge, attitude, and confidence of students and teachers.
GRK3 is a poor prognosticator and serves as a therapeutic target in advanced gastric adenocarcinoma
Authors: Li Yuan , Fan Yibo , Xu Jinbang , Huo Longfei , Scott Ailing W. , Jin Jiankang , Yang Boxuan , Shao Shan , Ma Lang , Wang Ying , Yao Xiaodan , Pool Pizzi Melissa , Sewastjanow Da Silva Matheus , Zhang Guoliang , Zhuo Lijuan , Cho Eun Jeong , Dalby Kevin N. , Shanbhag Namita D. , Wang Zhenning , Li Wenliang , Song Shumei , Ajani Jaffer A. 
Published: August 2022

AbstractBackgroundG protein-coupled receptor (GPCR) is the most targeted protein family by the FDA-approved drugs. GPCR-kinase 3 (GRK3) is critical for GPCR signaling. Our genomic analysis showed that GRK3 expression correlated with poor prognosis of gastric adenocarcinoma (GAC) patients. However, GRK3’s functions and clinical utility in GAC progression and metastases are unknown.MethodsWe studied GRK3 expression in normal, primary, and metastatic GAC tissues. We identified a novel GRK3 inhibitor, LD2, through a chemical-library screen. Through genetic and pharmacologic modulations of GRK3, a series of functional and molecular studies were performedin vitroandin vivo. Impact of GRK3 on YAP1 and its targets was determined.ResultsGRK3 was overexpressed in GAC tissues compared to normal and was even higher in peritoneal metastases. Overexpression (OE) of GRK3 was significantly associated with shorter survival. Upregulation of GRK3 in GAC cells increased cell invasion, colony formation, and proportion of ALDH1+cells, while its downregulation reduced these attributes. Further, LD2 potently and specifically inhibited GRK3, but not GRK2, a very similar kinase to GRK3. LD2 highly suppressed GAC cells’ malignant phenotypesin vitro. Mechanistically, GRK3 upregulated YAP1 in GAC tissues and its transcriptional downstream targets: SOX9, Birc5, Cyr61 and CTGF. Knockdown (KD) YAP1 rescued the phenotypes of GRK3 OE in GAC cells. GRK3 OE significantly increased tumor growth but LD2 inhibited tumor growth in the PDX model and dramatically suppressed peritoneal metastases induced by GRK3 OE.ConclusionsGRK3, a poor prognosticator for survival, conferred aggressive phenotype. Genetic silencing of GRK3 or its inhibitor LD2 blunted GRK3-conferred malignant attributes, suggesting GRK3 as a novel therapeutic target in advanced GAC.
AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes
Authors: Lau Tin Man Mandy , Lowe John , Pickles Timothy , Hood Kerenza , Kotecha Sailesh , Gillespie David 
Published: August 2022

Abstract
Background
The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described.

Methods and design
A double-blind, randomised, placebo-controlled trial of a 10-day course of intravenous azithromycin (20 mg/kg for 3 days; 10 mg/kg for 7 days) administered to preterm infants born at < 30 weeks’ gestational age across UK tertiary neonatal units. Following parental consent, infants are randomly allocated to azithromycin or placebo, with allocated treatment starting within 72 h of birth. The primary outcome is survival without moderate/severe CLD at 36 weeks’ postmenstrual age (PMA). Serial respiratory fluid and stool samples are being collected up to 21 days of life. The target sample size is 796 infants, which is based on detecting a 12% absolute difference in survival without moderate/severe CLD at 36 weeks’ PMA (90% power, two-sided alpha of 0.05) and includes 10% loss to follow-up.

Results
Baseline demographic and clinical characteristics will be summarised by treatment arm and in total. Categorical data will be summarised by numbers and percentages. Continuous data will be summarised by mean, standard deviation, if data are normal, or median, interquartile range, if data are skewed. Tests of statistical significance will not be undertaken for baseline characteristics. The primary analysis, on the intention to treat (ITT) population, will be analysed using multilevel logistic regression, within a multiple imputation framework. Adjusted odds ratios, 95% confidence intervals, and p-values will be presented. For all other analyses, the analysis population will be based on the complete case population, which is a modified ITT population. All analyses will be adjusted for gestational age and treatment arm and account for any clustering by centre and/or multiple births as a random effect.

Conclusion
We describe the statistical analysis plan for the AZTEC trial, including the analysis principles, definitions of the key clinical outcomes, methods for primary analysis, pre-specified subgroup analysis, sensitivity analysis, and secondary analysis. The plan has been finalised prior to the completion of recruitment.

Trial registration
ISRCTN registry ISRCTN11650227. Registered on 31 July 2018.
Comparison of various methods for validity evaluation of QSAR models
Authors: Shayanfar Shadi , Shayanfar Ali 
Published: August 2022

Abstract
Background
Quantitative structure–activity relationship (QSAR) modeling is one of the most important computational tools employed in drug discovery and development. The external validation of QSAR models is the main point to check the reliability of developed models for the prediction activity of not yet synthesized compounds. It was performed by different criteria in the literature.

Methods
In this study, 44 reported QSAR models for biologically active compounds reported in scientific papers were collected. Various statistical parameters of external validation of a QSAR model were calculated, and the results were discussed.

Results
The findings revealed that employing the coefficient of determination (r2) alone could not indicate the validity of a QSAR model. The established criteria for external validation have some advantages and disadvantages which should be considered in QSAR studies.

Conclusion
This study showed that these methods alone are not only enough to indicate the validity/invalidity of a QSAR model.