bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series
Authors: Tamura Ryota , Morimoto Yukina , Kosugi Kenzo , Sato Mizuto , Oishi Yumiko , Ueda Ryo , Kikuchi Ryogo , Nagashima Hideaki , Hikichi Tetsuro , Noji Shinobu , Kawakami Yutaka , Sasaki Hikaru , Yoshida Kazunari , Toda Masahiro 
Published: March 2020

Abstract
Background
The expression of vascular endothelial growth factor (VEGF)-A/ VAGF receptors (VEGFRs) signaling plays a pivotal role in the tumor angiogenesis and the development of the immunosuppressive tumor microenvironment in glioblastomas. We have previously conducted exploratory clinical studies investigating VEGFRs peptide vaccination with and without multiple glioma oncoantigens in patients with recurrent high-grade gliomas. Recently, an exploratory clinical investigation of VEGFRs peptide vaccination was conducted in patients with progressive neurofibromatosis type 2. Those studies suggested that cytotoxic T lymphocytes (CTLs) induced by the vaccination can directly kill a wide variety of cells associated with tumor growth, including tumor vessels, tumor cells, and immunosuppressive cells expressing VEGFR1 and/or 2. In the present study, synergistic activity of the combination of VEGFRs peptide vaccination with chemotherapy was evaluated.

Methods
We performed the first clinical trial to assess VEGFR1 and 2 vaccination along with temozolomide (TMZ) -based chemoradiotherapy for the patients with primary glioblastomas. Furthermore, histopathological changes after the vaccination were evaluated using paired pre- and post- vaccination specimens.

Results
The disappearance of radiographically enhanced lesion was observed in 2 patients after the vaccination, including one in which the methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was not observed. The histopathological findings of pre- and post-vaccination specimens demonstrated that tumor vessels showed negative or slight VEGFRs expressions after the vaccination and most endothelial cells were covered with PDGFR-β-positive pericytes. Notably, CTLs induced by VEGFRs peptide vaccination attacked not only tumor vessels but also tumor cells and regulatory T cells expressing VEGFRs even in recurrent tumors.

Conclusions
VEGFR1 and 2 vaccination may have a preliminary synergistic effect when administered with TMZ. The limitation of the present study was the paucity of the number of the samples. Further studies involving more patients are warranted to confirm the findings of this study.

Trial registration
This study was registered as UMIN000013381 (University Hospital Medical Information Network-Clinical Trial Registry: UMIN-CTR) on 5 March, 2014 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs031180170 on 1 March, 2019.
A phase II open label, randomised study of ipilimumab with temozolomide versus temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma: the Ipi-Glio trial protocol
Authors: Brown Nicholas F. , Ng Stasya M. , Brooks Claire , Coutts Tim , Holmes Jane , Roberts Corran , Elhussein Leena , Hoskin Peter , Maughan Tim , Blagden Sarah , Mulholland Paul 
Published: March 2020

AbstractBackgroundMedian survival for patients with glioblastoma is less than a year. Standard treatment consists of surgical debulking if feasible followed by temozolomide chemo-radiotherapy. The immune checkpoint inhibitor ipilimumab targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and has shown clinical efficacy in preclinical models of glioblastoma. The aim of this study is to explore the addition of ipilimumab to standard therapy in patients with glioblastoma.Methods/designIpi-Glio is a phase II, open label, randomised study of ipilimumab with temozolomide (Arm A) versus temozolomide alone (Arm B) after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma. Planned accrual is 120 patients (Arm A: 80, Arm B: 40). Endpoints include overall survival, 18-month survival, 5-year survival, and adverse events. The trial is currently recruiting in seven centres in the United Kingdom.Trial registrationISRCTN84434175. Registered 12 November 2018.
Lipid profile and risk of ovarian tumours: a meta-analysis
Authors: Onwuka Justina Ucheojor , Okekunle Akinkunmi Paul , Olutola Olaniyi Matthew , Akpa Onoja Matthew , Feng Rennan 
Published: March 2020

AbstractBackgroundExisting data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT.MethodsElectronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed usingI2statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias.ResultsTwelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis andI2statistics ranged between 97 and 99%. Mean circulating TC (− 16.60 [− 32.43, − 0.77]mg/dL;P = 0.04) and HDL (− 0.25[− 0.43, − 0.08]mmol/L;P = 0.005) were significantly lower among OT cases compared to non-OT cases.ConclusionDecreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.
Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and prognostic nutritional index for predicting clinical outcomes in T1–2 rectal cancer
Authors: Xia Li-jian , Li Wen , Zhai Jian-cheng , Yan Chuan-wang , Chen Jing-bo , Yang Hui 
Published: March 2020

Abstract
Background
Inflammation-related parameters have been revealed to have prognostic value in multiple caners. However, the significance of some inflammation-related parameters, including the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and prognostic nutritional index (PNI), remains controversial in T1–2 rectal cancer (RC).

Methods
Clinical data of 154 T1–2 RC patients were retrospectively reviewed. The cut-off values for NLR, PLR, LMR, and PNI were determined by receiver operating characteristic curves. The relationships of these parameters with postoperative morbidities and prognosis were statistically analysed.

Results
The optimal cut-off values for preoperative NLR, PLR, LMR and PNI were 2.8, 140.0, 3.9, and 47.1, respectively. Significant but heterogeneous associations were found between NLR, PLR, LMR and PNI and clinicopathological factors. In addition, high NLR, high PLR, and low PNI were correlated with an increased postoperative morbidity rate. Patients with high NLR/PLR or low LMR/PNI had lower OS and DFS rates. On multivariate analysis, only high NLR was identified as an independent risk factor for poor DFS.

Conclusions
NLR, PLR, and PNI are valuable factors for predicting postoperative complications in T1–2 RC patients. A preoperative NLR of more than 2.8 is an independent prognostic factor for poor DFS in T1–2 RC patients.
Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma
Authors: Zhou Jiangqiao , Wang Tianyu , Qiu Tao , Chen Zhongbao , Ma Xiaoxiong , Zhang Long , Zou Jilin 
Published: March 2020

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitin-specific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC.

Methods
Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells).

Results
USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival. USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by downregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK).

Conclusion
USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.
Age- and gender-specific trends in respiratory outpatient visits and diagnoses at a tertiary pediatric hospital in China: a 10-year retrospective study
Authors: Shi Peng , Zhang Xiaobo , Liu Lijuan , Tang Liangfeng , Li Jing , Wang Libo , Li Albert M. , Cao Yang , Xu Hong , Huang Guoying 
Published: March 2020

Abstract
Background
Respiratory infections are one of three leading causes of childhood mortality, and worldwide increase and recent plateau in childhood asthma has been reported. However, data on trends of respiratory diseases over long period of time is limited. This study aimed to determine the trends of respiratory disease outpatient visits (ROVs) and diagnoses (RODs) in one of the largest children’s teaching hospitals in China between 2009 and 2018.

Methods
A retrospective study based on routine administrative data was designed and implemented according to the RECORD statement. Demographic details and diagnoses of the outpatients < 18 years visiting the respiratory department of the hospital were extracted from the Hospital Information System. Age- and gender-specific trends were illustrated by calculating average annual growth rate (AAGR) for ROVs and comparing change of proportion for different RODs over time.

Results
There were 698,054 ROVs from 285,574 children (40.4% female). AAGR of ROVs was 15.2%. Children aged 4 to < 7 years had a faster increase than other age groups. Bronchitis (27.6%), pneumonia (18.5%), pneumonia affecting other systems (18.4%), asthma and status asthmaticus (10.7%), and vasomotor and allergic rhinitis (9.2%) accounted for 84.4% of all RODs. The proportion of bronchitis decreased across years, with the concomitant increasing trend in the proportion of pneumonia. Age-specific trend in diagnoses showed greater proportion of asthma in all visits for the children aged 7 to < 18 years than younger children. Gender-specific trend in diagnoses showed the proportion of asthma was greater for males but the AAGR was greater for females.

Conclusion
The persistent upward trend in ROVs was observed among children at different ages and a gender difference was also seen. In contrast to what has been reported, burden of asthma and allergies diseases continues to increase locally.
Physical activity and creativity of children and youths
Authors: Piya-amornphan Nitita , Santiworakul Anoma , Cetthakrikul Salila , Srirug Phatcharawadee 
Published: March 2020

Abstract
Background
Childhood is an important period for developing maturity in thinking. Accumulating evidence shows the association between physical activity and cognitive function. Although both the intelligence quotient and emotional quotient have been reported to be associated with physical activity, there is a limited amount of published research regarding the association between physical activity and cognitive function in children and youths. With respect to creativity, an important skill for the twenty-first century, little evidence on the creative quotient promotion in childhood is available. The present study, therefore, is designed to explore the correlation between physical activity and creativity.

Methods
The participants included 1447 students with different age groups in 34 schools from Southern Thailand. Age groups were categorized according to Thailand’s 2016 Report Card on Physical Activity for Children and Youth, where 521 students were aged 6–9 years, 487 students were aged 10–13 years, and 439 students were aged 14–17 years. Creativity was measured through the use of the Test for Creative Thinking-Drawing Production (TCT-DP). Active play, time with family and peers, and sedentary behavior were monitored by the Thailand Physical Activity Children Survey-the Student Questionnaire (TPACS-SQ).

Results
The correlation between the TCT-DP score representing creativity and active play was noticed in adolescents (r = 0.148, p = 0.001), but not found in participants aged 6–13 years. Active play was associated with time with family and peers in all age groups (r = 0.485, p <  0.001).

Conclusions
The present data supports the idea that optimal physical activity is required during childhood for developing thinking process. Promotion of active play with family and peers may facilitate creativity skills.
Co-occurrence of mutations in KIF7 and KIAA0556 in Joubert syndrome with ocular coloboma, pituitary malformation and growth hormone deficiency: a case report and literature review
Authors: Niceta Marcello , Dentici Maria Lisa , Ciolfi Andrea , Marini Romana , Barresi Sabina , Lepri Francesca Romana , Novelli Antonio , Bertini Enrico , Cappa Marco , Digilio Maria Cristina , Dallapiccola Bruno , Tartaglia Marco 
Published: March 2020

Abstract
Background
Joubert syndrome is a recessive neurodevelopmental disorder characterized by clinical and genetic heterogeneity. Clinical hallmarks include hypotonia, ataxia, facial dysmorphism, abnormal eye movement, irregular breathing pattern cognitive impairment and, the molar tooth sign is the pathognomonic midbrain-hindbrain malformation on magnetic resonance imaging. The disorder is predominantly caused by biallelic mutations in more than 30 genes encoding proteins with a pivotal role in morphology and function of the primary cilium. Oligogenic inheritance or occurrence of genetic modifiers has been suggested to contribute to the variability of the clinical phenotype. We report on a family with peculiar clinical spectrum Joubert syndrome molecularly and clinically dissecting a complex phenotype, in which hypogonadism, pituitary malformation and growth hormone deficiency occur as major features.

Case presentation
A 7 year-old male was enrolled in a dedicated “Undiagnosed Patients Program” for a peculiar form of Joubert syndrome complicated by iris and retinochoroidal coloboma, hypogonadism pituitary malformation, and growth hormone deficiency. The molecular basis of the complex phenotype was investigated by whole exome sequencing. The concomitant occurrence of homozygosity for mutations in KIF7 and KIAA0556 was identified, and the assessment of major clinical features associated with mutations in these two genes provided evidence that these two independent events represent the cause underlying the complexity of the present clinical phenotype.

Conclusion
Beside the clinical variability of Joubert syndrome, co-occurrence of mutations in ciliopathy-associated genes may contribute to increase the clinical complexity of the trait.
Service user and family participation in mental health policy making in Timor-Leste: a qualitative study with multiple stakeholders
Authors: Hall Teresa , Kakuma Ritsuko , Palmer Lisa , Minas Harry , Martins João , Armstrong Greg 
Published: March 2020

AbstractBackgroundParticipation in mental health system strengthening by people with mental health problems and their families is a cornerstone of people-centred mental health care, yet there is a dearth of research about participation from low- and middle-income countries (LMICs), particularly from the Asia Pacific region. Hence, this study aimed to assess the current situation, challenges, enabling factors and future actions for service user and family participation in mental health policy making in Timor-Leste.MethodsIn-depth interviews were conducted with 85 adults (≥18 years) who were: (1) mental health service users (n = 20) and their families (n = 10); (2) government decision makers (n = 10); (3) mental health and social service providers (n = 23); (4) civil society (n = 9); and (5) other groups (n = 13). Interview data was analysed using framework analysis.ResultsThere was limited service user, family and community participation in mental health policy making in Timor-Leste. Perceptions that policy making is a technical exercise and that people with mental health problems lack cognitive capacity, and a lack of supportive mechanisms challenged participation. Enabling factors were a strong focus on human rights within the social sector, and existing mechanisms for advocacy and representation of people with disabilities in social policy making. Participants suggested bolstering civil society representation of people with mental health problems, and increasing mental health awareness and literacy, including government competencies to facilitate service user participation.ConclusionThe findings highlight the need for theoretical and practical focus on the role of family within mental health system development in LMICs. Global mental health research and practice should adopt a critical approach to mental health service user and family participation to ensure that the concept and strategies to achieve this are embedded in LMIC knowledge.
Adverse event reports in patients taking psychiatric medication during pregnancy from spontaneous reports in Japan and the United States: an approach using latent class analysis
Authors: Anzai Tatsuhiko , Takahashi Kunihiko , Watanabe Michiko , Mochizuki Mayumi , Murashima Atsuko 
Published: March 2020

Abstract
Background
Little is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US).

Methods
We summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications.

Results
The proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for ‘general disorders and administration site conditions’ from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for ‘injury, poisoning, and procedural complications’ from the class of single psychiatric medication (OR = 2.8).

Conclusions
The main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results.
Dispensation of attention deficit hyperactivity disorder (ADHD) medications in patients receiving opioid agonist therapy; a national prospective cohort study in Norway from 2015 to 2017
Authors: Vold Jørn Henrik , Aas Christer , Skurtveit Svetlana , Odsbu Ingvild , Chalabianloo Fatemeh , Halmøy Anne , Johansson Kjell Arne , Fadnes Lars Thore 
Published: March 2020

Abstract
Background
It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated.

Methods
Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to assess the associations between ADHD medication, and OAT opioid use, and dispensations of other potentially addictive drugs and DAAs against hepatitis C infection.

Results
A total of 9235 OAT patients were included. The proportion of patients who were dispensed ADHD medication increased from 3.5 to 4.6% throughout the study period. The three most dispensed CAS were short- and intermediate-acting methylphenidate (55%), lisdexamphetamine (24%), and dexamphetamine (17%) in 2017. Buprenorphine, rather than methadone, as OAT opioid (adjusted odds ratio: 1.6, CI: 1.2–2.1) was associated with being dispensed ADHD medication. Among patients who received CAS and OAT opioids each calendar year, the dispensed doses of methylphenidate increased from 63 mg/day in 2015 to 76 mg/day in 2017 (p = 0.01). Sixty percent of patients receiving ADHD medications were also dispensed other addictive drugs concomitantly in 2017. Similar results were found in 2015 and 2016.

Conclusion
Co-prescription of ADHD medications was low among patients on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed.