bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of HOMER3 in liver cancer progression.
Authors: Makondi Precious Takondwa 
Published: October 2019

89 Background: Liver cancer (LC) is in the seventh most common cancer and the fourth largest cause of cancer deaths. Although significant progress has been made in the prevention and treatment of viral hepatitis; alcoholic liver disease, obesity and diabetes are now emerging as major causes for LC. Recently there has been increase in identification of biomarkers which can predict LC risk and disease progression, but the roles of HOMER3 gene in LC are not known. Methods: First the expression of HOMER3 between normal and tumor tissues was determined using The Cancer Genome Atlas (TCGA), Genetic Expression Omnibus (GEO) and protein atlas datasets. HOMER3 expression at different clinical stage and overall survival (OS) was also determined. The role of HOMER3 on OS in relation to cancer stage, hepatitis virus infection and alcohol intake was also determined. STRING database determined HOMER3 interaction network and TCGA was used to verify the correlation status, and the roles of the network genes on OS. The pathways enriched by HOMER3 were determined by Gene Set Enrichment Analysis (GSEA). Results: HOMER3 was significantly highly expressed in tumor tissues as compared to normal tissues. The expression of HOMER3 correlated positively with clinical stage, with highest expression in advanced stages (Stage 3 and 4), and high HOMER3 expression was associated with poor OS. HOMER3’ s high expression was associated with poor OS in advanced stage, alcohol intake, and in those negative of viral hepatitis infection. HOMER3 interacted with HOMER1, SHANK1, GRM5, GRM1, DLGAP1, SHANK2, DLG4, SHANK3, DLG2 and DLGAP4, with positive correlation to HOMER1, SHANK1, GRM5, GRM1, DLGAP1, DLG4 and DLGAP4 and negative correlation to SHANK2, SHANK3 and DLG2. HOMER1 and DLGAP4 high expression were associated with poor OS while SHANK2, SHANK3 and DLG2 high expression were associated with favorable OS. GRM5 and GRM1 high expression were associated with favorable OS despite being positively correlated with HOMER3. ECM receptor interaction and Notch signaling were the upregulated pathways while Metabolism of xenobiotics by cytochrome p450 and PPAR signaling were the downregulated pathways. Conclusions: HOMER3 may is have a role in liver cancer progression of which its targeting may improve LC outcome.
A pilot study of using smartphone application versus routine follow up for patients' care in advanced non-small cell lung cancer (NSCLC).
Authors: Prasongsook Naiyarat , Seetalarom Kasan , Saichaemchan Siriwimon , Udomdamrongkul Kitipong 
Published: October 2019

9 Background: Web-based patient reported outcome (PRO) improved quality of life (QoL), and overall survival (OS) in patients with advanced NSCLC who were treating with specific therapy. Lung Cancer Care application is a mobile application program that provides patients with individually tailored information on patient reported outcome. This study aims to invent a novel mobile application evaluating PRO for Thai NSCLC patients, and to evaluate the validity of mobile application. Methods: Our mobile application-based PRO was designed for monitoring quality of life. The validity of the application was tested following guidelines for translating, and validating a questionnaire. The quality of life score (FACT-L score). After the validated mobile application-based PRO, patients with advanced NSCLC were randomized to use mobile application-based PRO versus routine follow-up. The primary endpoint was quality of life (QoL). Secondary endpoint was OS. Results: Thirty-three patients with advanced NSCLC were enrolled. The mean of FACT-L score at baseline in mobile application-based PRO arm and routine follow up arm was similar (90.08 ± 5.66 vs 91.78 ± 5.26, p-value= 0.82). Patients with mobile application group had more FACT-L score at 3 months than patients with routine follow up arm (106 ± 5.97 vs 99.96 ± 5.74, p-value = 0.07). There was a trend towards increased in different mean of FACT-L score at baseline and 3 months in patients with mobile application compared to patients with routine follow up ( p-value = 0.05). The median follow-up time was 5.43 months, patients with mobile application had longer median OS than patients with routine follow up (4 months vs 2.9 months, p-value = 0.5). Conclusions: Lung Cancer Care application based on self-reported symptoms is a novel electronic device for real-time patient care monitoring. Our study results showed trend towards improved quality of life from using this novel mobile application. However, there was small samples for pilot testing, the relatively large sampling errors may reduce the statistical power needed to validate this tool.
New generation of oncolytic herpesviruses embodying immunotherapeutic genes encoding IL-12 and anti-PD-1 antibody.
Authors: Zhou Grace , Ni Dongyao , Yan Runbin , Chen Xiaoqing , Liu Xianjie , Tang Yuxin , Ma Jie 
Published: October 2019

92 Background: Systemic administration of checkpoint inhibitors alone and especially concurrent with intratumoral administration of oncolytic herpes simplex viruses (oHSV) have a major impact on cancer therapy marred by rare failures of healthy organs. Methods: We constructed 3 recombinant oHSVs expressing no immunomodulatory genes (T1 series), murine or human IL-12 (T2 series) and murine or human IL-12 and anti-PD-1 antibody (T3 series). We compared 1) the oncolytic effects of a single or multiple intratumoral injection(s) of T1, T2 and T3 series oHSVs, 2) the effectiveness of intratumoral injection of T3 oHSV with systemic administration of anti PD-1 ab and IL12 alone or in combinations with T1. Results: Insertion of gene encoding PD-1 Ab significantly augmented the oncolytic activity of oHSV bereft of immunostimulatory genes (T1 series) or expressing IL-12 alone (T2 series). In syngeneic mice the T3 series oHSV expressing murine IL-12 and PD-1 Ab was effective against a variety of murine tumors. Concurrent with enhanced cytolytic activity the T3 induced significant intratumoral accumulation of IL-12, PD-1 Ab and IFN-γ. Consistent with an earlier report of an inverse correlation between the volume of the tumor and the quantity of retained IFN-γ. The most effective oncolytic effect resulted from the administration of T3855 expressing both IL12 and anti PD-1 antibody or T2850 concurrently with intraperitoneal administration of anti PD-1 antibody alone. The least effective were single intraperitoneal administration of IL12 or PD-1 antibody. Intratumoral injection of T3 oHSV was most effective against murine tumors in comparison of either systemic administration of anti PD-1 ab and IL12 or intratumoral injection of T1 in combinations of systemic administration of anti PD-1 ab and IL12. Conclusions: We report the marriage in a single therapeutic agent of three distinct cancer therapies: the targeting of cancer cells by oncolytic viruses, the stimulation of immune system by IL12, and the production of immunotherapeutic antibodies against PD-1. The significant finding reported in this article is that the anti-tumor responses remain concentrated in the tumor environment.
Concordance between a clinical decision-support system and treatments selected by clinicians as a function of cancer type or stage.
Authors: Suwanvecho Suthida , Suwanrusme Harit , Issarachai Surasit , Jirakulaporn Tanawat , Taechakraichana Nimit , Lungchukiet Palita , Thanakarn Nittaya , Decha Wimolrat , Boonpakdee Wisanu , Wongrattananon Pattanawadee , Preininger Anita , Arriaga Yull Edwin , Solomon Metasebya , Wang Suwei , Dankwa-Mullan Irene , Esquivel Jaime , Patel Vimla L , Shortliffe Edward , Jackson Gretchen , Kiatikajornthada Narongsak 
Published: October 2019

95 Background: Watson for Oncology (WFO) is an artificial intelligence (AI) based clinical decision-support tool trained by Memorial Sloan Kettering. This retrospective observational study of breast, lung, colon and rectal cancer examined the concordance of treatment options provided by WFO to treatments selected by clinicians at Bumrungrad International Hospital (BIH) as a function of stage or cancer type. Methods: Concordance between WFO treatment options and treatments selected by BIH clinicians (WFO-BIH concordance) was defined as identical or equally acceptable treatments, as determined by a panel of experts blinded to the source of treatment. Relationships between stage or type of cancer and WFO-BIH concordant treatments were evaluated by Chi-squared analysis. Results: Analysis revealed a statistically significant association ( P = 0.02) between cancer stage and concordance. For all 4 cancer types combined, stages I-III demonstrated higher concordance than stage IV. A highly significant association ( P < 0.001) between concordance and cancer type was identified. Colon cancer demonstrated the highest concordance, followed by rectal, lung and breast cancer. Reasons for discordance, when given, related to oncologist or patient preferences, and treatment availability. Conclusions: BIH clinicians tended to agree more with WFO therapeutic options for stage I-III cancers and colon cancer in general, as compared to relatively less agreement for stage IV cancers and breast cancer in general, suggesting the need to understand reasons for discordance among all cancer types and stages. An AI tool, trained by experts in the U.S., provides treatment options consistent with some therapies selected in international settings, but preferences and treatment availability may affect choices made in practice. [Table: see text]
Risk scoring model to predict recurrence in locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NACT).
Authors: Agrawal Sushma , Mishra Prabhakar , Lal Punita , Agarwal Gaurav , Agarwal Amit , Mishra Anjali , Mishra saroj K 
Published: October 2019

98 Background: Complete response (CR) to NACT portends favorable long term outcomes in LABC. There is a need for a tool to risk categorise patients for recurrence risk (RR), so that intensification of treatment can be offered to women with high risk of recurrence. Methods: A prospectively maintained database of LABC (between January 2007 to December 2012), who received NACT followed by definitive surgery, radiotherapy and endocrine therapy in endocrine sensitive disease was retrospectively analyzed for clinico-pathological and treatment factors affecting disease free survival (DFS). A risk scoring model was developed on the basis of beta coefficients of identified independent risk factors for DFS. Results: The incidence of loco-regional relapse was 8% and that of distant metastases was 32% in a dataset of 206 patients at a median follow-up of 47 months (IQR 24-62 mo). The independent risk factors for recurrence were index T stage [HR 1.8 (0.9-3.6)], N stage [HR 1.7 (0.4 – 4.7)], grade [HR 1.8 (0.8-4.2)], age less than and more than 40 years [HR 1.6 (0.4-0.9)], pathologic CR [HR 4.3 (1.7- 10.7)], intrinsic subtype [HR 2.2 (1.3-3.7)], and type of surgery (BCS vs MRM) [HR 2.2 (1.3-3.6)]. The ROC of the model for the prediction of recurrence was 0.67 (95 % CI: 0.61-0.75). The results of this model were validated by dividing the population into 3 risk groups: low risk (score less than 12), intermediate risk group (score between 13-15), high risk group (score 16 or more). The chances of recurrence are 16% versus 34% versus 57% in low, intermediate and high risk group respectively. Presence of three risk factors implies low risk, five intermediate and more than five high risk. Conclusions: The risk scoring model developed by us predicts RR and can be used for selecting patients for treatment intensification in high risk category.
Stereotactic body radiotherapy (SBRT) or surgery in early stage (I & II) non small cell lung cancer (NSCLC).
Authors: Koyi Hirsh , Daham Kameran , Al-Ameri Mamdoh , Branden Eva 
Published: October 2019

99 Background: For patients with NSCLC clinical stages I and II disease with no medical contraindications, surgery is treatment of choice showing 5-year survival rates of about 60–80% for stage I and 40–50% for stage II, respectively. However, for patients who are medically or technically unfit for surgery and for patients refusing surgery, SBRT is an alternative with local control rates > 90% at 3 years. Methods: Medical journals in all patients with stage I or II NSCLC who were underwent surgery and treated with SBRT at the Department of oncology or thoracic surgery, Karolinska University Hospital, Sweden from 2003 to 2010 were retrospectively reviewed. Results: In all, 267 (74.8%) underwent surgery and 90 (25.2%) were treated with SBRT. Mean, median and range of age among the surgery group was 69.2, 70.0 and 41-85 years, while in the SBRT group, these figures were 77.6, 79.0 and 52-90 years. The difference in age between the groups was significant (p < 0.001).There were significantly more comorbidites in the SBRT group. Among the surgery group, 90.2% were smokers or former smokers. The figures for SBRT group was 91.1%. The difference in smoking habits between the groups was not significant (p < 0.713). There was a significant difference in performance status (PS) between the groups (p < 0.001) with with PS 0-1 in 99.3% in the surgery group compared with 66.7% in the SBRT group. There was a significant difference in lung function with median FEV1 2.11 liter in surgery group compared to 1.3 in the SBRT group. The figures for median FEV1% was 85.0% respectively 57.0%. The median overall survival was 7.7 years for the surgery group and 3.72 years for the SBRT group (p < 0.001). Five years survival was 65.5% in the surgery group and 31.6% in the SBRT group (p < 0.001). Conclusions: The much worse median overall survival in the SBRT group can be explained by the selection of patients, but still, a median survival for nearly 4 years in an elderly group with so many comorbidities and a poor PS indicates that SBRT has been of value.
Simulated Costs of the ASCO Patient-Centered Oncology Payment Model in Medicare Beneficiaries With Newly Diagnosed Advanced Ovarian Cancer
Authors: Moss Haley A. , Havrilesky Laura J. , Wang Frances F. , Georgieva Mihaela V. , Hendrix Laura H. , Dinan Michaela A. 
Published: October 2019

PURPOSE: Efforts to curb the rising costs of cancer care while improving quality include alternative payment models (APMs), which offer incentives to reduce avoidable spending and provide high-quality and cost-efficient care. The impact of proposed APMs has not been quantified in real-world practice. In this study, we evaluated ASCO’s Patient-Centered Oncology Payment (PCOP) model in existing fee-for-service (FFS) Medicare beneficiaries to understand the magnitude of potential cost savings. MATERIALS AND METHODS: SEER-Medicare data were used to identify women with advanced ovarian cancer diagnosed between 2000 and 2012 who either (1) underwent primary debulking surgery followed by chemotherapy or (2) received neoadjuvant chemotherapy followed by surgery. Medicare payments in each cohort were used to compare FFS and PCOP and to estimate the potential for cost savings across health care services received, including outpatient emergency department visits, hospitalizations, and imaging. RESULTS: Three thousand seven hundred seventy-seven primary debulking surgery and 866 neoadjuvant chemotherapy patients were included in the study, with mean total costs of $75,433 and $95,138 in 2016 US$, respectively Most costs were related to chemotherapy or hospitalization. Additional PCOP-related payments would be offset if hospitalizations could be reduced by 11.6% or imaging claims by 88%. CONCLUSION: APMs have the potential to reduce costs of current FFS reimbursement via either a large reduction in imaging or a modest reduction in hospitalizations during treatment of ovarian cancer. PCOP is a reasonable payment structure for oncologists if the additional payments can provide the necessary resources to invest in improved coordination of care.
Plasma Renin Measurements are Unrelated to Mineralocorticoid Replacement Dose in Patients With Primary Adrenal Insufficiency
Authors: Pofi Riccardo , Prete Alessandro , Thornton-Jones Vivien , Bryce Jillian , Ali Salma R , Faisal Ahmed S , Balsamo Antonio , Baronio Federico , Cannuccia Amalia , Guven Ayla , Guran Tulay , Darendeliler Feyza , Higham Claire , Bonfig Walter , de Vries Liat , Bachega Tania A S S , Miranda Mirela C , Mendonca Berenice B , Iotova Violeta , Korbonits Màrta , Krone Nils P , Krone Ruth , Lenzi Andrea , Arlt Wiebke , Ross Richard J , Isidori Andrea M , Tomlinson Jeremy W 
Published: October 2019

Abstract

Context
No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency.

Objective
To explore the relationship between mineralocorticoid (MC) replacement dose, plasma renin concentration (PRC), and clinically important variables to determine which are most helpful in guiding MC dose titration in primary adrenal insufficiency.

Design
Observational, retrospective, longitudinal analysis.

Patients
A total of 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency were recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (149 adults and 55 children) and 39 adult patients with Addison disease (AD) were analysed.

Main outcome measures
PRC, electrolytes, blood pressure (BP), and anthropometric parameters were used to predict their utility in optimizing MC replacement dose.

Results
PRC was low, normal, or high in 19%, 36%, and 44% of patients, respectively, with wide variability in MC dose and PRC. Univariate analysis demonstrated a direct positive relationship between MC dose and PRC in adults and children. There was no relationship between MC dose and BP in adults, while BP increased with increasing MC dose in children. Using multiple regression modeling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in MC dose was able to predict potassium, but not BP or PRC.

Conclusions
The relationship between MC dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last MC dose, adherence, and concomitant medications. Our data suggest that MC titration should not primarily be based only on PRC normalization, but also on clinical parameters such as BP and electrolyte concentration.
Neonatal iron distribution and infection susceptibility in full term, preterm and low birthweight babies in urban Gambia: study protocol for an observational study.
Authors: Cross James H. , Jarjou Ousman , Mohammed Nuredin Ibrahim , Prentice Andrew M. , Cerami Carla 
Published: October 2019

Background: Neonatal infection is the third largest cause of death in children under five worldwide. Nutritional immunity is the process by which the host innate immune system limits nutrient availability to invading organisms. Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Our previously published data shows that, during the first 24 hours of life, full-term neonates have reduced overall serum iron. Transferrin saturation decreases rapidly from 45% in cord blood to ~20% by six hours post-delivery. Methods: To study neonatal nutritional immunity and its role in neonatal susceptibility to infection, we will conduct an observational study on 300 full-term normal birth weight (FTB+NBW), 50 preterm normal birth weight (PTB+NBW), 50 preterm low birth weight (PTB+LBW) and 50 full-term low birth weight (FTB+LBW), vaginally-delivered neonates born at Kanifing General Hospital, The Gambia. We will characterize and quantify iron-related nutritional immunity during the early neonatal period and use ex vivo sentinel bacterial growth assays to assess how differences in serum iron affect bacterial growth. Blood samples will be collected from the umbilical cord (arterial and venous) and at serial time points from the neonates over the first week of life. Discussion: Currently, little is known about nutritional immunity in neonates. In this study, we will increase understanding of how nutritional immunity may protect neonates from infection during the first critical days of life by limiting the pathogenicity and virulence of neonatal sepsis causing organisms by reducing the availability of iron. Additionally, we will investigate the hypothesis that this protective mechanism may not be activated in preterm and low birth weight neonates, potentially putting these babies at an enhanced risk of neonatal infection. Trial registration: clinicaltrials.gov (NCT03353051) 27/11/2017
Antiprogestines
Authors: Sergheyev P. V. , Kareva Ye. N. , Tkacheva N. Yu. , Vysotsky M. M. 
Published: October 2019

Antiprogestins are steroid compounds that have a high ability to bind to progesterone cell receptors and thus prevent their binding to endogenous steroid hormone.
The first achievements in the search for progesterone antagonists were obtained in the laboratories of well-known companies Roussel-Uclaf and Schering AG, where hundreds of Hp-arylsteroid derivatives were synthesized, of which the most common were mifepristone (RU 38486), lilopristone (ZK 08734), onapriston (ZK 08200 )
At present, antiprogestins are used as implantation inhibitors, contraceptives, drugs used in Itsenko-Cushing's disease.
In most cases, antiprogestins are administered to women of active reproductive age.
DAMPAK KEBIJAKAN ISBAT NIKAH TERHADAP PERKAWINAN SIRI DAN CAMPURAN DI KABUPATEN CIANJUR
Authors: Solihah Cucu , Yulianah Yuyun , Nur Hilman , Rozi Mumuh M. 
Published: October 2019

Kebijakan isbat nikah berlaku terhadap perkawinan dalam rangka penyelesaian perceraian, hilangnya akta nikah, adanya keraguan tentang sah atau tidaknya salah satu syarat perkawinan, dan terhadap perkawinan yang terjadi sebelum berlakunya Undang-Undang No. 1 Tahun 1974 juga terhadap Perkawinan yang dilakukan oleh mereka yang tidak mempunyai halangan perkawinan menurut Undang-Undang No. 1 Tahun 1974, namun kebijakan tersebut juga dimanfaatkan oleh pasangan suami istri yang menikah dengan cara siri dan perkawinan campuran. Metode penelitian menggunakan pendekatan normatif yuridis berupa analisis deskriptif. Sumber data yang digunakan adalah data primer dan data sekunder berupa peraturan yang relevan dengan penelitian. Hasil penelitian menunjukkan adanya indikasi pemanfaatan celah hukum dari kebijakan isbat nikah oleh masyarakat dan warga Negara asing dalam menikahi wanita Indonesia guna menghindari syarat administrasi perkawinan.
Coron Problem for Nonlocal Equations Involving Choquard Nonlinearity
Authors: Goel Divya , Rădulescu Vicenţiu D. , Sreenadh K. 
Published: October 2019

Abstract
We consider the following Choquard equation:

{

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)

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)

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,

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0

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,

\left\{\begin{aligned} \displaystyle-\Delta u&\displaystyle=\Bigg{(}\int_{% \Omega}\frac{|u(y)|^{2^{*}_{\mu}}}{|x-y|^{\mu}}\,dy\Bigg{)}|u|^{2^{*}_{\mu}-2}% u&&\displaystyle\phantom{}\text{in }\Omega,\\ \displaystyle u&\displaystyle=0&&\displaystyle\phantom{}\text{on }\partial% \Omega,\end{aligned}\right.

where Ω is a smooth bounded domain in

ℝ
N

{\mathbb{R}^{N}}

(

N
≥
3

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),

2
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{2^{*}_{\mu}=\frac{2N-\mu}{N-2}}

. This paper is concerned with the existence of a positive high-energy solution of the above problem in an annular-type domain when the inner hole is sufficiently small.