bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of Osimertinib for patients with radiotherapy-naïve CNS metastasis of non-small cell lung cancer: treatment rationale and protocol design of the OCEAN study (LOGIK 1603/WJOG 9116L)
Authors: Wakuda Kazushige , Yamaguchi Hiroyuki , Kenmotsu Hirotsugu , Fukuda Minoru , Takeshita Masafumi , Suetsugu Takayuki , Kirita Keisuke , Ebi Noriyuki , Hataji Osamu , Miura Satoru , Chibana Kenji , Okamoto Isamu , Yoshimura Kenichi , Nakagawa Kazuhiko , Yamamoto Nobuyuki , Sugio Kenji 
Published: May 2020

Abstract
Background
Patients with activating epidermal growth factor receptor (EGFR) mutations are highly responsive to EGFR-tyrosine kinase inhibitors (TKIs). However, it has been reported that approximately 15–30% of patients treated with EGFR-TKIs experience central nervous system (CNS) progression, and patients with EGFR mutations exhibit a higher incidence of brain metastasis than those without such mutations. The efficacy of osimertinib for treating CNS metastasis has been reported, but its efficacy for CNS metastasis in radiotherapy-naïve patients is unclear.

Methods
In the present prospective two-cohort phase II trial, 65 patients (T790M cohort, 40 patients; first-line cohort, 25 patients) with radiotherapy-naïve CNS metastasis of EGFR mutation-positive non-small cell lung cancer (NSCLC) will be included. Patients will be treated once-daily with osimertinib 80 mg. The primary endpoint is the response rate of brain metastasis as assessed using the PAREXEL criteria. Key secondary endpoints are progression-free survival and the response rate of brain metastasis as assessed using the RECIST criteria. We will exploratorily analyze the relationships of the blood concentration of osimertinib with its efficacy against brain metastasis of NSCLC and the accumulation of osimertinib in cerebrospinal fluid and evaluate tumor-derived DNA from plasma specimens for mutations in EGFR and other genes. Recruitment, which in October 2016, is ongoing.

Discussion
Although previous reports revealed the efficacy of osimertinib for CNS metastasis, these reports only involved subgroup analysis, and the efficacy of osimertinib for patients with previously untreated CNS metastasis remains unclear. The OCEAN study is the only trial of osimertinib for patients with untreated brain metastasis of NSCLC. This study should provide novel data about osimertinib. If the results of the OCEAN study are positive, then avoidance of radiotherapy will be recommended to patients harboring EGFR mutations and brain metastasis.

Trial registration
UMIN identifier: UMIN000024218 (date of initial registration: 29 September 2016). jRCT identifier: jRCTs071180017 (date of initial registration: 13 February 2019).
Quantification of the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy: development of the modified Gleason grade grouping (mGGG) model
Authors: Taguchi Satoru , Uemura Yukari , Fujimura Tetsuya , Morikawa Teppei , Naito Akihiro , Kawai Taketo , Suzuki Motofumi , Kume Haruki , Fukuhara Hiroshi 
Published: May 2020

Abstract
Background
While the new Gleason grade grouping (GGG), which started in 2016, has been widely validated in prostate cancer, it does not incorporate the concept of tertiary Gleason pattern 5. Furthermore, no study has “quantified” the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy.

Methods
We reviewed 1022 men with adjuvant-treatment-naïve prostate cancer who underwent radical prostatectomy between 2005 and 2017. The primary endpoint was biochemical recurrence-free survival, defined as two consecutive prostate-specific antigen measurements ≥0.2 ng/ml after surgery. The individual quantitative risk score (IQRS) of each amount (primary/secondary/tertiary) of each Gleason pattern (3/4/5) was calculated using the Cox regression model. On the basis of the IQRS, the modified Gleason grade grouping (mGGG) model was developed. As a robustness analysis of the mGGG model, salvage treatment-free survival was also assessed.

Results
During a median follow-up of 45 months, 229 of 1022 (22.4%) patients developed biochemical recurrence. The IQRS of each Gleason pattern was as follows: primary 5, 1.81 points (hazard ratio [HR] 6.13); secondary 5, 1.37 points (HR 3.92); tertiary 5, 0.87 points (HR 2.39); primary 4, 1.07 points (HR 2.91); secondary 4, 0.79 points (HR 2.21); and any Gleason pattern 3, 0 points (HR 1). Based on the IQRS, the mGGG model was developed, which classified patients into the following five groups: I (3 + 3 or less); II (3 + 4); III (4 + 3); IV (3 + 4 + t5, 4 + 3 + t5, 3 + 5, 5 + 3, and 4 + 4); V (4 + 4 + t5, 4 + 5, 5 + 4, and 5 + 5). The c-index for biochemical recurrence-free survival was significantly improved from 0.655 of the original GGG model to 0.672 of the mGGG model (P < 0.05). In the robustness analysis, the c-index for salvage treatment-free survival was also significantly improved from 0.619 of the original GGG model to 0.638 of the mGGG model (P < 0.05).

Conclusions
The quantitative risk of tertiary (< 5%) Gleason pattern 5 is slightly higher than that of secondary (5–50%) Gleason pattern 4. Our newly developed mGGG model more accurately predicts outcomes after radical prostatectomy than the original GGG model.
Prdx1 promotes the loss of primary cilia in esophageal squamous cell carcinoma
Authors: Chen Qiongzhen , Li Jinmeng , Yang Xiaoning , Ma Junfeng , Gong Fanghua , Liu Yu 
Published: May 2020

Abstract
Background
Loss of primary cilia is frequently observed in tumor cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction, the inability to exit the cell cycle, and promotion of tumor cell invasion. Primary cilia loss also occurs in esophageal squamous cell carcinoma (ESCC) cells, but the molecular mechanisms that explain how ESCC cells lose primary cilia remain poorly understood.

Methods
Inhibiting the expression of Prdx1 in the ESCC cells to detect the up-regulated genes related to cilium regeneration and down-regulated genes related to cilium disassembly by Gene chip. And, mice and cell experiments were carried to confirm the role of the HEF1-Aurora A-HDAC6 signaling axis in ESCC.

Results
In this study, we found that silencing Peroxiredoxin 1 (Prdx1) restores primary cilia formation, and over-expressing Prdx1 induces primary cilia loss in ESCC cells. We also showed that the expression of Prdx1 regulates the action of the HEF1-Aurora A-HDAC6 signaling axis to promote the disassembly of primary cilia, and suppression of Prdx1 results in decreased tumor formation and tumor mass volume in vivo.

Conclusions
These results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.
Germline whole exome sequencing of a family with appendiceal mucinous tumours presenting with pseudomyxoma peritonei
Authors:   Australian Ovarian Cancer Study Group, Lung Mei Sim , Mitchell Catherine A. , Doyle Maria A. , Lynch Andrew C. , Gorringe Kylie L. , Bowtell David D. L. , Campbell Ian G. , Trainer Alison H. 
Published: May 2020

Abstract
Background
Familial cases of appendiceal mucinous tumours (AMTs) are extremely rare and the underlying genetic aetiology uncertain. We identified potential predisposing germline genetic variants in a father and daughter with AMTs presenting with pseudomyxoma peritonei (PMP) and correlated these with regions of loss of heterozygosity (LOH) in the tumours.

Methods
Through germline whole exome sequencing, we identified novel heterozygous loss-of-function (LoF) (i.e. nonsense, frameshift and essential splice site mutations) and missense variants shared between father and daughter, and validated all LoF variants, and missense variants with a Combined Annotation Dependent Depletion (CADD) scaled score of ≥10. Genome-wide copy number analysis was performed on tumour tissue from both individuals to identify regions of LOH.

Results
Fifteen novel variants in 15 genes were shared by the father and daughter, including a nonsense mutation in REEP5. None of these germline variants were located in tumour regions of LOH shared by the father and daughter. Four genes (EXOG, RANBP2, RANBP6 and TNFRSF1B) harboured missense variants that fell in a region of LOH in the tumour from the father only, but none showed somatic loss of the wild type allele in the tumour. The REEP5 gene was sequenced in 23 individuals with presumed sporadic AMTs or PMP; no LoF or rare missense germline variants were identified.

Conclusion
Germline exome sequencing of a father and daughter with AMTs identified novel candidate predisposing genes. Further studies are required to clarify the role of these genes in familial AMTs.
Comparison of power-free-chop and phaco-chop techniques for moderate nuclei
Authors: Yao Lin , Bai Haiqing 
Published: May 2020

Abstract
Background
To compare the intraoperative and postoperative effects of power-free-chop and phaco-chop techniques for moderate nuclei in phacoemulsification surgery.

Methods
Sixty patients were evaluated in 2 groups. The power-free-chop technique was performed in Group 1 (30 eyes), and the phaco-chop technique was performed in Group 2 (30 eyes). There were no significant differences between these 2 groups. The cumulative dissipated energy (CDE), time to achieve maximum vision, corneal thickness variation, and time to return to the preoperative values were collected. All parameters were statistically compared in these 2 groups by using the chi-square test and the independent-sample t-test.

Results
The CDE was 5.53 ± 1.92 J in Group 1 and 7.02 ± 1.77 J in Group 2. After the operation, the mean time to recover to the maximum vision was 2.80 ± 1.42 days in Group 1 and 3.80 ± 1.92 days in Group 2. The mean postoperative corneal thickness increased 36.9 ± 14.74 μm in Group 1 and 46.20 ± 20.67 μm in Group 2. The mean time to return to preoperative pachymetry values was 3.73 ± 1.70 days and 4.83 ± 2.11 days in Group 1 and Group 2, respectively. There were significant differences in these parameters between the groups.

Conclusions
The power-free-chop technique had fewer negative effects on the corneal endothelium, as less ultrasound power was used for moderate nucleus cases. This can accelerate the functional healing process and the return to preoperative physiologic values.
The effect of yoga on sleep quality and insomnia in women with sleep problems: a systematic review and meta-analysis
Authors: Wang Wei-Li , Chen Kuang-Huei , Pan Ying-Chieh , Yang Szu-Nian , Chan Yuan-Yu 
Published: May 2020

Abstract
Background
To examine the effectiveness and safety of yoga of women with sleep problems by performing a systematic review and meta-analysis.

Methods
Medline/PubMed, ClinicalKey, ScienceDirect, Embase, PsycINFO, and the Cochrane Library were searched throughout the month of June, 2019. Randomized controlled trials comparing yoga groups with control groups in women with sleep problems were included. Two reviewers independently evaluated risk of bias by using the risk of bias tool suggested by the Cochrane Collaboration for programming and conducting systematic reviews and meta-analyses. The main outcome measure was sleep quality or the severity of insomnia, which was measured using subjective instruments, such as the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), or objective instruments such as polysomnography, actigraphy, and safety of the intervention. For each outcome, a standardized mean difference (SMD) and confidence intervals (CIs) of 95% were determined.

Results
Nineteen studies in this systematic review included 1832 participants. The meta-analysis of the combined data conducted according to Comprehensive Meta-Analysis showed a significant improvement in sleep (SMD = − 0.327, 95% CI = − 0.506 to − 0.148, P < 0.001). Meta-analyses revealed positive effects of yoga using PSQI scores in 16 randomized control trials (RCTs), compared with the control group in improving sleep quality among women using PSQI (SMD = − 0.54; 95% CI = − 0.89 to − 0.19; P = 0.003). However, three RCTs revealed no effects of yoga compared to the control group in reducing insomnia among women using ISI (SMD = − 0.13; 95% CI = − 0.74 to 0.48; P = 0.69). Seven RCTs revealed no evidence for effects of yoga compared with the control group in improving sleep quality for women with breast cancer using PSQI (SMD = − 0.15; 95% CI = − 0.31 to 0.01; P = 0.5). Four RCTs revealed no evidence for the effects of yoga compared with the control group in improving the sleep quality for peri/postmenopausal women using PSQI (SMD = − 0.31; 95% CI = − 0.95 to 0.33; P = 0.34). Yoga was not associated with any serious adverse events.

Discussion
This systematic review and meta-analysis demonstrated that yoga intervention in women can be beneficial when compared to non-active control conditions in term of managing sleep problems. The moderator analyses suggest that participants in the non-breast cancer subgroup and participants in the non-peri/postmenopausal subgroup were associated with greater benefits, with a direct correlation of total class time with quality of sleep among other related benefits.
The bat meat chain and perceptions of the risk of contracting Ebola in the Mount Cameroon region
Authors: Akem Efuet Simon , Pemunta Ngambouk Vitalis 
Published: May 2020

Abstract
Background
Local people’s interaction with bats render them vulnerable to Ebola Virus Disease (EVD). This paper examines perceptions of risk involved in the hunting, handling, processing and consumption of bat meat in the Mount Cameroon region of Southwest Cameroon. It focuses on the myriad cultural beliefs, gendered patterns of activity and institutional arrangements in which the bat meat production chain is embedded.

Methods
We conducted 30 ethnographic interviews with a sample of purposively selected men and women involved in the bat meat trade. The interviews were tape recorded, transcribed verbatim and inductive analysis was performed on the data.

Findings
The findings suggests that more urban men than villagers and hunters consume bat meat. Different practices and behaviours expose the mostly uneducated, young, single men and women to the risk of Ebola infection depending on their differential level of intervention in the human-bat interaction and value chain linking hunters, sellers and customers. The killing of bats with the mouth during hunting expose hunters (young men) while the preparation of bat carcasses for consumption also put women, (mostly young and unmarried) at risk.

Conclusions
This study demonstrates that the complexity and nuances of gender, poverty and Ebola outcomes predispose some marginal groups to the risk of infection with zoonotic diseases. There is the need to improve public health intervention and health education among the rural masses in the Mount Cameroon region.
Health problems and healthcare service utilisation amongst homeless adults in Africa- a scoping review
Authors: Osei Asibey Benedict , Conroy Elizabeth , Marjadi Brahmaputra 
Published: May 2020

AbstractBackgroundHomelessness is a growing concern as it affects a large number of people worldwide. Individuals and families experiencing homelessness are vulnerable in terms of health and underutilise health services. Despite being a global problem, not much is known about the range and breath of literature exploring health problems and health care service utilisation among homeless adults in Africa.ObjectivesTo identify the nature and scope of existing evidence on physical and mental health, and health service utilisation among homeless adults in Africa. The review aimed to examine how research is conducted, identify gaps, guide future research, and make recommendations for development and implementation of policies and practices.MethodsA search of articles and reports involving six databases: Scopus, MEDLINE, CINAHL, PubMed, African Journal Online, and Google Scholar was conducted from June 2018 to February 2019. Studies published between 1980 and 2019 that examined the health problems and health service utilisation among homeless adults in Africa were considered. Manual search in reference lists and grey literature was also done to add reports. Data was extracted manually using a charting developed. A descriptive analysis and narrative synthesis were performed.ResultsOf 761 records found, 14 satisfied the pre-determined inclusion and exclusion criteria. Three themes emerged from the studies: Physical health problems, mental health problems; and healthcare services utilisation. Of the 14 included studies, nine studied and reported physical health problems such as sexually transmitted infections, injuries and disabilities, respiratory and cardiac diseases. Five studies explored mental health problems such as psychotic disorders, mood disorders, self-harm and suicidal behaviour. Only five studies investigated utilisation of different types of health care services among homeless people.ConclusionsEvidence shows that homeless adults suffered from a range of physical and mental health problems, and underutilisation of health care services. However, there is lack of information on the complex interrelationship between homelessness and health, as well as differences in prevalence of health problems among the various sub-groups of homeless. There is also lack of information regarding utilisation other important healthcare services such as mental health services, alcohol and drugs services, and accident and emergency service, and future researches should address that. Also, attention should be given to intervention models for complex and effective physical and psychiatric care as well as social support to address the homeless people’s health vulnerabilities.
Factors associated with injuries among preschool children in Egypt: demographic and health survey results, 2014
Authors: Mohammed Zeinab , Aledhaim Ali , AbdelSalam Eman Mohammed , El-Setouhy Maged , EL-Shinawi Mohamed , Hirshon Jon Mark 
Published: May 2020

Abstract
Background
Childhood injuries are a significant and growing global public health problem, often with high morbidity and, at times, mortality. A large proportion of injuries in preschool children occur in or around the home. We aimed to identify socioeconomic and demographic factors associated with preschool children injuries in Egypt.

Methods
Secondary data analysis were done for the Egyptian Demographic and Health Surveys (EDHS), 2014. Potential associated factors were measured from data on child welfare and questions on the prevalence of accidents and injuries of preschool children. These data were linked to the children demographic data, maternal age at marriage, working status of the mother, and questions on childcare arrangements.

Results
Out of the 634 injured children, 520 (83.4%) children required medical care for their injuries. The most common reported injury was an open wound 288 (45.5%), followed by fractures 237 (35.7%), burns 124 (19.7%), electrical shock 12 (1.9%) and other unknown types of injury 15 (2.4%). There was a positive correlation between injury and child’s age, household wealth, mother’s age at marriage, and unsupervised children or children left in the care of a minor.

Conclusion
Leaving children unsupervised or in the presence of other young children is significantly associated with the occurrence of child injuries.
Protocol for the trial to establish a causal linkage between mycotoxin exposure and child stunting: a cluster randomized trial
Authors: Phillips Erica , Ngure Francis , Smith Laura E. , Makule Edna , Turner Paul C. , Nelson Rebeca , Kimanya Martin , Stoltzfus Rebecca , Kassim Neema 
Published: May 2020

AbstractBackgroundThe number of stunted children has fallen globally but continues to increase in Africa. Stunting is estimated to contribute to 14–17% of child deaths under 5 years of age and is a risk factor for poor cognitive and motor development and educational outcomes. Inadequate dietary intake and disease are thought to be the immediate causes of undernutrition and stunting. However, improving infant diets through complementary feeding interventions has been shown to only modestly reduce stunting. Multiple observational studies demonstrate a dose response relationship between fetal and post-natal aflatoxin exposure and reduced linear growth.MethodsThis community-based cluster randomized trial will measure the effect of a reduced aflatoxin diet on length-for-age Z scores at 18 months in central Tanzania. All 52 health facilities in the Kongwa District of Dodoma Region were randomized into two groups. Starting at 6 months of age, participants in the intervention group receive a low-aflatoxin pre-blended porridge flour containing maize and groundnut (ratio 4:1 respectively) and low-aflatoxin groundnut flour, whereas in the control group the same porridge mix and groundnut flour are promoted through education but acquired by the household. Both groups will receive the same infant and young child feeding education and a thermos flask. A total of 3120 infants between 6 weeks and 3 months of age will be recruited into the study over 1 year. Data will be collected four times – at recruitment and when the infants are 6, 12 and 18 months of age. In a cohort of 600 infants, additional data will be collected at 9 and 15 months of age. The primary outcome is length-for-age at 18 months. Secondary outcomes include the Z scores for weight-for-age, middle upper arm circumference and head circumference, and the blood biomarker aflatoxin-albumin in the full sample, with the urine biomarker aflatoxin M1 analyzed in the cohort only.DiscussionBetter understanding the etiology of childhood stunting can lead to more appropriate interventions and policies to further reduce linear growth faltering and meet the Sustainable Development Goals.Trial registrationNCT03940547, (April 24, 2019).
Association between type of exercise and health-related quality of life in adults without activity limitations: a nationwide cross-sectional study
Authors: Choi Min-Jung , Park Yong Gyu , Kim Yang Hyun , Cho Kyung Hwan , Nam Ga Eun 
Published: May 2020

Abstract
Background
Exercise is known to be associated with health-related quality of life (HRQoL), however, evidence on the association between type of exercise and HRQoL in the general population is limited. We performed this study to investigate the association of exercise types and their combinations with HRQoL in Korean adults.

Methods
We analyzed data from 13,437 adults aged ≥19 years without activity limitations who had participated in the 5th Korea National Health and Nutrition Examination Survey 2010–2012. As per the American College of Sports Medicine guideline, exercise types were categorized into eight groups: walking (W), flexibility (F), resistance (R), W + F, W + R, F + R, and W + F + R exercise groups and a non-exercise group. The European Quality of Life-5 Dimension (EQ-5D) index and the European Quality of Life Visual Analogue Scale (EQ-VAS) were used to assess HRQoL.

Results
The mean age of participants was 42.8 ± 0.2 years. The proportion of participants in the non-exercise group was the highest (34.7%); among the exercise groups, the walking group was the most prevalent (16.9%) and the W + R group was the least (1.2%). In analysis of covariance, the mean EQ-5D index in W (0.875), W + F (0.878), F + R (0.877), and W + F + R (0.876) groups was significantly higher compared with that in non-exerciser group (0.869) (p < 0.05). The mean EQ-VAS score in the W (64.064), F (64.427), W + F (65.676), F + R (65.811), and W + F + R (67.110) groups was higher than that in the non-exercise group (62.396) (p < 0.05). No difference was observed between R and W + R groups and non-exercise group with regard to the EQ-5D index and EQ-VAS score.

Conclusions
The W (for 30 min at least five times a week), W + F, F + R (at least two days a week), and W + F + R groups showed higher HRQoL than the non-exercise group. This study may be helpful in the development of public exercise interventions, which could help enhance HRQoL in adults.