bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum fibroblast growth factor 19 serves as a potential novel biomarker for hepatocellular carcinoma
Authors: Maeda Takahiro , Kanzaki Hiroaki , Chiba Tetsuhiro , Ao Junjie , Kanayama Kengo , Maruta Susumu , Kusakabe Yuko , Saito Tomoko , Kobayashi Kazufumi , Kiyono Soichiro , Nakamura Masato , Ogasawara Sadahisa , Suzuki Eiichiro , Ooka Yoshihiko , Nakamoto Shingo , Nakagawa Ryo , Muroyama Ryosuke , Kanda Tatsuo , Maruyama Hitoshi , Kato Naoya 
Published: November 2019

Abstract

Background
Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the potential of serum FGF19 as a novel tumor marker of HCC based on a sandwich enzyme-linked immunosorbent assay (ELISA).

Methods
The serum FGF19 levels of 304 patients with HCC was measured by ELISA. The serum levels of existing markers, including alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were determined by chemiluminescence enzyme immunoassay. Both diagnostic value of FGF19 and its changes after curative ablation therapy was further examined.

Results
The median FGF19 levels in controls, chronic liver disease patients, and primary HCC patients, were 78.8 pg/mL, 100.1 pg/mL, and 214.5 pg/mL, respectively. The subsequent receiver operating characteristic curves (ROC) successfully determined an optimal cut-off value of 200.0 pg/mL. The area under the ROC curve (AUC) of FGF19 for HCC detection was comparable to those of AFP and DCP. Of importance, FGF19 showed higher sensitivity for the detection of small HCC (solitary cancer with diameter < 20 mm) than those of existing markers. In addition, 43 out of 79 cases (54.4%) with normal AFP and DCP (so-called “double negative HCC”) exhibited serum FGF19 level ≥ 200 pg/mL. In 45 HCC patients treated with curative ablation therapy, serum FGF19 levels changed from 257.4 pg/mL to 112.0 pg/mL after the treatment.

Conclusion
Our findings reveal that FGF19 can be a potential novel biomarker for HCC. Although FGF19 is not necessarily a substitute for existing markers, it may help improve the prognosis in HCC patients owing to its resourceful use in various aspects of HCC management and treatment.
Can ELABELA be a novel target in the treatment of chronic lymphocytic leukaemia?
Authors: Acik Didar Yanardag , Bankir Mehmet , Baylan Filiz Alkan , Aygun Bilal 
Published: November 2019

Abstract

Background
It has been shown that bcl2, bcl-XL and mcl-1 protein levels are high in chronic lymphocytic leukemia cells, and resultantly, apoptosis does not occur chronic lymphocytic leukemia cells. Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein coupled receptor called apelin receptor. Studies have shown that ELA inhibits apoptosis by inhibiting apoptotic proteins and activating anti-apoptotic proteins. Proteins and genes involved in apoptosis are valuable for targeted cancer therapy. We hypothesized that serum levels may be increased in patients with chronic lymphocytic leukemia based on the antiapoptotic effect of ELA. We compared serum ELABELA levels of healthy volunteers and patients with chronic lymphocytic leukemia. We aimed to draw attention to a new molecule worthy of research in targeted cancer treatment.

Methods
Forty two untreated CLL patients and 41 healthy volunteers were included in the study. Serum ELA levels were measured by using enzyme-linked immunosorbent assay kits (Dhanghai Sunred Biological Technology co. Ltd), automated ELISA reader (Thermo Scientific, FİNLAND) and computer program (Scanlt for Multiscan F.C.2.5.1) in accordance with the manufacturer’s instructions. Statistical analysis was done by Statistical Package for Social Sciences for Windows 20 (IBM SPSS Inc., Chicago, IL) ve MedCalc programs. ELA and variables related to CLL were correlated with Spearman correlation anlysis test. ROC analysis and Youden index method were used to determine a cut off point for ELA. All p-values were 2-sided with statistical significance at 0.05 alpha levels.

Results
In our study, we found that serum ELA levels were significantly higher in patients with CLL.

Conclusions
This study highlights that ELA targeting may be a potential therapeutic option for treating CLL.
Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study
Authors: Lakatos Andrea , Kolossváry Márton , Szabó Miklós , Jermendy Ágnes , Barta Hajnalka , Gyebnár Gyula , Rudas Gábor , Kozák Lajos R. 
Published: November 2019

Abstract

Background
Identification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE.

Methods
A retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score < 85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors.

Results
MRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n = 78). 36% (n = 39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR = 6.2292; CI95% = [1.2642; 30.6934], p = 0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR = 6.2496; CI95% = [1.2018; 32.4983], p = 0.0294), while ICH remained to have no significant effect.

Conclusion
HIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.
Sex-related change in BMI of 15- to 16-year-old Norwegian girls in cross-sectional studies in 2002 and 2017
Authors: Bjertnaes Asborg A. , Grundt Jacob H. , Juliusson Petur B. , Markestad Trond J. , Strand Tor A. , Holten-Andersen Mads N. 
Published: November 2019

Abstract

Background
The prevalence of overweight and obesity (OWOB) has stabilized in some countries, but a portion of children with high body mass index (BMI) may have become heavier. This study aimed to describe the distributions of BMI and the point prevalence of OWOB in Norwegian adolescents in 2002 and 2017.

Methods
A cross-sectional study involving 15- to 16-year-old adolescents in Oppland, Norway, was undertaken in 2002 and 2017. We calculated their BMI, BMI z-scores (BMIz), and the prevalence of OWOB.

Results
The mean BMI increased from 20.7 to 21.4 (p < 0.001) for girls but remained unchanged at 21.5 vs 21.4 (p = 0.80) for boys. The prevalence of OWOB increased from 9 to 14% among girls (difference 5, 95% CI: 2, 8) and from 17 to 20% among boys (difference 3, 95% CI: − 1, 6%). The BMI density plots revealed similar shapes at both time points for both sexes, but the distribution for girls shifted to the right from 2002 to 2017.

Conclusion
Contrary to previous knowledge, we found that the increase in OWOB presented a uniform shift in the entire BMI distribution for 15–16-year-old Norwegian girls and was not due to a larger shift in a specific subpopulation in the upper percentiles.
A review of changes to the attention deficit/hyperactivity disorder age of onset criterion using the checklist for modifying disease definitions
Authors: Sanders Sharon , Thomas Rae , Glasziou Paul , Doust Jenny 
Published: November 2019

Abstract

Background
Widening definitions of health conditions have the potential to affect millions of people and should only occur when there is strong evidence of benefit. In the last version of the Diagnostic and Statistical Manual of Mental Disorders (DSM), the DSM-5 Committee changed the Attention Deficit Hyperactivity Disorder (ADHD) age of onset criterion in two ways: raising the age of symptom onset and removing the requirement for symptoms to cause impairment. Given concerns about ADHD prevalence and treatment rates, we aimed to evaluate the evidence available to support these changes using a recently developed Checklist for Modifying Disease Definitions.

Methods
We identified and analysed research informing changes to the DSM-IV-TR ADHD age of onset criterion. We compared this evidence to the evidence recommended in the Checklist for Modifying Disease Definitions.

Results
The changes to the DSM-IV-TR age of onset criterion were based on a literature review (publicly available as a 2 page document with online table of included studies), which we appraised as at high risk of bias. Estimates of the change in ADHD prevalence resulting from change to the age of onset criterion were based on a single study that included only a small number of children with ADHD (n = 68) and only assessed the impact of change to the age component of the criterion. No evidence was used by, or available to the Committee regarding the impact on prevalence of removal of the requirement for impairment, or the effect of the criterion changes on diagnostic precision, the prognosis of, or the potential benefits or harms for individuals diagnosed by the new, but not old criterion.

Conclusions
The changes to the age of onset criterion were based on minimal research evidence that suffered from either high risk of bias or poor applicability. The minimal documentation available makes it difficult to judge the rigor of the process behind the criterion changes. Use of the Checklist for Modifying Disease Definitions would assist future proposed modifications of the DSM ADHD criteria, provide guidance on the studies needed to inform potential changes and would improve the transparency and documentation of the process.
Measuring and correcting bias in indirect estimates of under-5 mortality in populations affected by HIV/AIDS: a simulation study
Authors: Quattrochi John , Salomon Joshua A. , Hill Kenneth , Castro Marcia C. 
Published: November 2019

Abstract

Background
In populations that lack vital registration systems, under-5 mortality (U5M) is commonly estimated using survey-based approaches, including indirect methods. One assumption of indirect methods is that a mother’s survival and her children’s survival are not correlated, but in populations affected by HIV/AIDS this assumption is violated, and thus indirect estimates are biased. Our goal was to estimate the magnitude of the bias, and to create a predictive model to correct it.

Methods
We used an individual-level, discrete time-step simulation model to measure how the bias in indirect estimates of U5M changes under various fertility rates, mortality rates, HIV/AIDS rates, and levels of antiretroviral therapy. We simulated 4480 populations in total and measured the amount of bias in U5M due to HIV/AIDS. We also developed a generalized linear model via penalized maximum likelihood to correct this bias.

Results
We found that indirect methods can underestimate U5M by 0–41% in populations with HIV prevalence of 0–40%. Applying our model to 2010 survey data from Malawi and Tanzania, we show that indirect methods would underestimate U5M by up to 7.7% in those countries at that time. Our best fitting model to correct bias in U5M had a root median square error of 0.0012.

Conclusions
Indirect estimates of U5M can be significantly biased in populations affected by HIV/AIDS. Our predictive model allows scholars and practitioners to correct that bias using commonly measured population characteristics. Policies and programs based on indirect estimates of U5M in populations with generalized HIV epidemics may need to be reevaluated after accounting for estimation bias.
Neighbour noise annoyance is associated with various mental and physical health symptoms: results from a nationwide study among individuals living in multi-storey housing
Authors: Jensen Heidi A. R. , Rasmussen Birgit , Ekholm Ola 
Published: November 2019

AbstractBackgroundNoise exposure is considered a stressor that may potentially exert negative health effects among the exposed individuals. On a population basis, the most prevalent and immediate response to noise is annoyance, which is an individually experienced phenomenon that may activate physiological stress-responses and result in both physical and mental symptoms. Health implications of traffic noise have been investigated thoroughly, but not of neighbour noise. The aim of the present study was to examine the associations between neighbour noise annoyance and eight different physical and mental health symptoms.MethodsCross-sectional data from the Danish Health and Morbidity Survey 2017 were used. The present study included a random sample of 3893 adults living in multi-storey housing. Information on neighbour noise annoyance and various health symptoms (e.g. pain in various body parts, headache, sleeping problems, depression, and anxiety) during the past two weeks was obtained by self-administered questionnaires. The question on neighbour noise annoyance and health symptoms, respectively, had three possible response options: ‘Yes, very annoyed/bothered’, ‘Yes, slightly annoyed/bothered’, ‘No’. The associations between neighbour noise annoyance and very bothering physical and mental health symptoms were investigated using multiple logistic regression models.ResultsBeing very annoyed by neighbour noise was significantly associated with higher odds of being very bothered by all eight health symptoms (adjusted OR = 1.73–3.32, allp-values < 0.05) compared to individuals not annoyed by noise from neighbours. Statistically significant interactions were observed between sex and two of the eight health symptoms. Among women, a strong association was observed between neighbour noise annoyance and being very bothered by pain or discomfort in the shoulder or neck, and in the arms, hands, legs, knees, hips or joints. Among men, no associations were observed.ConclusionsBased on the findings from this study, neighbour noise annoyance is strongly associated with eight different physical and mental health symptoms. Future studies are encouraged to 1) determine the direction of causality using a longitudinal design, 2) explore the biological mechanisms explaining the sex-specific impact of neighbour noise annoyance on symptoms of musculoskeletal pain or discomfort and the other outcomes as well.
Differential expression of histamine receptors in the bladder wall tissues of patients with bladder pain syndrome/interstitial cystitis – significance in the responsiveness to antihistamine treatment and disease symptoms
Authors: Shan Hui , Zhang Er-Wei , Zhang Peng , Zhang Xiao-Dong , Zhang Ning , Du Peng , Yang Yong 
Published: November 2019

Abstract

Background
Activation of mast cells plays an important role in the pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC). Histamine, a mast cell-derived mediators, induced inflammation and hypersensitivity of the bladder. The present study investigated the expressions of histamine receptors in the bladder wall tissues of patients with BPS/IC, and its association with the effectiveness of antihistamine therapy and disease symptoms.

Methods
Bladder tissues were collected from 69 BPS/IC patients and 10 control female patients. The expression of H3R in BPS/IC was further examined in an independent cohort of 10 female patients with BPS/IC and another 10 age-matched female patients. Immunohistochemistry, Western blotting, and quantitative RT-PCR were performed to quantify the expressions of histamine receptors. Statistical analyses of the correlation of histamine receptor expression with antihistamine therapy outcome and severity of disease symptoms were also performed.

Results
The expression of four histamine receptors was significantly elevated in BPS/IC (H1R, P < 0.001; H2R, P = 0.031; H3R, P = 0.008; H4R, P = 0.048). Western blotting revealed that H3R were significantly reduced in the patients, whereas the mRNA levels of H3R were significantly increased. The patients were further divided into antihistamine responders (n = 38) and nonresponders (n = 22). No significant correlation was found in the expression of histamine receptors between responder and nonresponder groups. However, significant correlations between OLS and H1R (P = 0.003) and H3R (P = 0.045) were found.

Conclusion
The present study showed that expression of all the 4 histamine receptors were elevated in BPS/IC. There were no statistical significant correlations between the expression levels of the four different histamine receptors and the treatment outcome of antihistamine therapy (amtitriptyline or cimetidine).
Retzius-sparing robot-assisted laparoscopic radical prostatectomy: functional and early oncologic results in aggressive and locally advanced prostate cancer
Authors: Nyarangi-Dix Joanne Nyaboe , Görtz Magdalena , Gradinarov Georgi , Hofer Luisa , Schütz Viktoria , Gasch Claudia , Radtke Jan Philipp , Hohenfellner Markus 
Published: November 2019

Abstract

Background
Retzius-sparing robot-assisted laparoscopic radical prostatectomy (rsRARP) allows entire prostatectomy procedure via the pouch of Douglas. In low- and intermediate-risk prostate cancer (PCa) there is level 1 evidence that the Retzius-sparing approach impacts early continence recovery. Since specific data on aggressive and locally advanced cancer is lacking and avoiding rsRARP is presently suggested, we investigated urinary and sexual recovery, perioperative complications and early oncologic outcomes after rsRARP in this particular cohort.

Methods
Prospectively collected data of 50 consecutive men (median age 66 years) with high-risk PCa who underwent rsRARP in a single institution was analysed retrospectively. The follow-up for all patients was 12 months after surgery.

Results
3 vs. 12 months after surgery, 82% vs. 98% of men used no pad or one safety pad and 50% vs. 72% used no pad. 89% of patients did not observe a decline of continence if postoperative radiotherapy was carried out.
Considering the 17 preoperatively potent patients who underwent bi- or unilateral nerve-sparing surgery, 41% reported their first sexual intercourse within 1 year after rsRARP.
84% of patients had ≥pT3a disease and 42% positive surgical margins. A lymphadenectomy was done in 94% of patients with a median lymph node removal of 15 and lymph node metastasis in 13%.
34% underwent adjuvant radiotherapy and 22% adjuvant androgen deprivation therapy (ADT). 1-year recurrence-free survival was 96%, including 25% of patients on adjuvant or salvage ADT.

Conclusions
RsRARP in high-risk PCa is feasible and results in excellent continence rates, even after postoperative radiotherapy. The potency rates are promising but need further clarification in larger cohorts. Reliable oncologic outcomes require longterm follow-up and are awaited.
Langerhans cells in hypospadias: an analysis of Langerin (CD207) and HLA-DR on epidermal sheets and full thickness skin sections
Authors: Haid Bernhard , Reider Daniela , Nägele Felix , Spinoit Anne-Françoise , Pechriggl Elisabeth , Romani Nikolaus , Fritsch Helga , Oswald Josef 
Published: November 2019

Abstract

Background
Hypospadias are among the most common genital malformations. Langerhans Cells (LCs) play a pivotal role in HIV and HPV infection. The migration of LC precursors to skin coincides with the embryonic period of hypospadias development and genetic alterations leading to the formation of hypospadias impact the development of ectodermally derived tissues. We hypothesized that this might be associated with a difference in frequency or morphology of epidermal and dermal LCs in hypospadias patients.

Methods
A total of 43 patients from two centers were prospectively included into this study after parental consent and ethics approval. Epidermal and dermal sheets were prepared from skin samples of 26 patients with hypospadias, 13 patients without penile malformations and 4 patients with penile malformations other than hypospadias. Immunofluorescence staining of sheets was performed with anti-HLA-DR-FITC and anti-CD207/Langerin-A594 antibodies. Skin sections from 11 patients without penile malformation and 11 patients with hypospadias were stained for Langerin. Frequencies as well as morphology and distribution of epidermal and dermal LCs on sheets and sections were microscopically evaluated. Cell counts were compared by unpaired t-tests.

Results
There was no difference in frequency of epidermal LCs, Neither on sheets (873 ± 61 vs. 940 ± 84LCs/mm2, p = 0.522) nor on sections (32 ± 3 vs. 30 ± 2LCs/mm2, p = 0.697). Likewise, the frequency of dermal LCs (5,9 ± 0,9 vs. 7.5 ± 1.3LCs/mm2, p = 0.329) was comparable between patients with hypospadias and without penile malformation. No differences became apparent in subgroup analyses, comparing distal to proximal hypospadias (p = 0.949), younger and older boys (p = 0.818) or considering topical dihydrotestosterone treatment prior to surgery (p = 0.08). The morphology of the LCs was not different comparing hypospadias patients with boys without penile malformations.

Conclusions
LCs are present in similar frequencies and with a comparable morphology and distribution in patients with hypospadias as compared to children without penile malformations. This suggests that patients with hypospadias are not different from patients with normal penile development considering this particular compartment of their skin immunity.