bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in Prostate Cancer Incidence and Mortality in Lower Saxony (Germany) and Groningen Province (Netherlands): Potential Impact of Prostate-Specific Antigen Testing
Authors: Kappen Sanny , de Bock Geertruida H. , Sirri Eunice , Vohmann Claudia , Kieschke Joachim , Winter Alexander 
Published: May 2021

BackgroundProstate cancer (PCa) is the most frequent cancer among men in Europe. Differences in PCa incidence around the world can be partly explained by variations in recommendations for prostate-specific antigen (PSA), particularly for early detection. For example, the PSA testing policy is more conservative in the Netherlands than in Germany. To better understand the relationship between PSA testing recommendations and PCa incidence, stage distribution, and mortality, we compared these variables over time between Lower Saxony in northwestern Germany and the neighboring province of Groningen in the Netherlands.MethodsPopulation data, tumor stage- and age group-specific PCa incidence (ICD-10 C61) and mortality rates for Lower Saxony and Groningen were obtained from the Lower Saxony Epidemiological Cancer Registry, the Netherlands Comprehensive Cancer Organization, and Statistics Netherlands for 2003–2012. Incidence and mortality rates per 100,000 person-years were age-standardized (ASR, old European standard). Trends in age-standardized incidence rates (ASIR) and mortality rates (ASMR) for specific age groups were assessed using joinpoint regression.ResultsThe mean annual PCa ASIR between 2003 and 2012 was on average 19.9% higher in Lower Saxony than in Groningen (120.5 vs. 100.5 per 100,000), while the mean annual ASMR was on average 24.3% lower in Lower Saxony than in Groningen (21.5 vs. 28.4 per 100,000). Between 2003 and 2012, the average annual percentage change (AAPC) in PCa incidence rates did not change significantly in either Lower Saxony (−1.8%, 95% CI −3.5, 0.0) or Groningen (0.2%, 95% CI −5.0, 5.7). In contrast, the AAPC in mortality rate decreased significantly during the same time period in Lower Saxony (−2.5%, 95% CI −3.0, −2.0) but not in Groningen (0.1%, 95% CI −2.4, 2.6).ConclusionsHigher PCa incidence and lower PCa-related mortality was detected in Lower Saxony than in Groningen. Although recommendations on PSA testing may play a role, the assessed data could not offer obvious explanations to the observed differences. Therefore, further investigations including data on the actual use of PSA testing, other influences (e.g., dietary and ethnic factors), and better data quality are needed to explain differences between the regions.
Prevalence of Growth Restriction at Birth for Newborns With Congenital Heart Defects: A Population-Based Prospective Cohort Study EPICARD
Authors: Ghanchi Ali , Rahshenas Makan , Bonnet Damien , Derridj Neil , LeLong Nathalie , Salomon Laurent J. , Goffinet Francois , Khoshnood Babak 
Published: May 2021

Background and Objectives: Congenital heart defects (CHD) and growth restriction at birth are two major causes of childhood and adult morbidity and mortality. The aim of this study was to assess the overall risk of growth restriction at birth, as measured by its imperfect proxy small (&lt; 10th percentile) for gestational age (SGA), for newborns with CHD.Methods: Using data from a population-based cohort of children born with CHD, we assessed the risk of growth restriction at birth using SGA and severe SGA (3rd percentile). To compare the odds of SGA and severe SGA across five specific major CHD, we used ordinal logistic regression using isolated, minor (non-operated) ventricular septal defect (VSD) as the control group.Results: The overall proportion of SGA for “isolated” CHD (i.e., those not associated with other anomalies) was 13% (95% CI, 12–15%), which is 30% higher than what would be expected in the general population (i.e., 10%). The risk of severe SGA was 5% (95% CI, 4–6%) as compared with the expected 3% in the general population. There were substantial differences in the risk of overall SGA and more so severe SGA across the different CHD. The highest risk of SGA occurred for Tetralogy of Fallot (adjusted OR 2.7, 95% CI, 1.3–5.8) and operated VSD (adjusted OR 2.1, 95% CI, 1.1–3.8) as compared with the control group of minor (non-operated) VSD.Conclusion: The overall risks of both SGA and severe SGA were higher in isolated CHD than what would be expected in the general population with substantial differences across the subtypes of CHD. These results may provide a clue for understanding the underlying mechanisms of the relation between alterations in fetal circulation associated with different types of CHD and their effects on fetal growth.
Pharmacokinetic Characteristics, Tissue Bioaccumulation and Toxicity Profiles of Oral Arsenic Trioxide in Rats: Implications for the Treatment and Risk Assessment of Acute Promyelocytic Leukemia
Authors: Liu Wensheng , Wang Bin , Zhao Yilei , Wu Zhiqiang , Dong Andi , Chen Hongzhu , Lin Liwang , Lu Jing , Hai Xin 
Published: May 2021

Oral arsenic trioxide (ATO) has demonstrated a favorable clinical efficiency in the treatment of acute promyelocytic leukemia (APL). However, the pharmacokinetic characteristics, tissue bioaccumulation, and toxicity profiles of arsenic metabolites in vivo following oral administration of ATO have not yet been characterized. The present study uses high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) to assess the pharmacokinetics of arsenic metabolites in rat plasma after oral and intravenous administration of 1 mg kg−1 ATO. In addition, the bioaccumulation of arsenic metabolites in blood and selected tissues were evaluated after 28 days oral administration of ATO in rats at a dose of 0, 2, 8, and 20 mg kg−1 d−1. The HPLC-HG-AFS analysis was complemented by a biochemical, hematological, and histopathological evaluation conducted upon completion of ATO treatment. Pharmacokinetic results showed that arsenite (AsIII) reached a maximum plasma concentration rapidly after initial dosing, and the absolute bioavailability of AsIII was 81.03%. Toxicological results showed that the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white blood cells (WBC) in the 20 mg kg−1 d−1 ATO group were significantly increased compared to the control group (p &lt; 0.05). The distribution trend of total arsenic in the rat was as follows: whole blood &gt; kidney &gt; liver &gt; heart. Dimethylated arsenic (DMA) was the predominant bioaccumulative metabolite in the whole blood, liver, and heart, while monomethylated arsenic (MMA) was the predominant one in the kidney. Collectively, these results revealed that oral ATO was rapidly absorbed, well-tolerated, and showed organ-specific and dose-specific bioaccumulation of arsenic metabolites. The present study provides preliminary evidence for clinical applications and the long-term safety evaluation of oral ATO in the treatment of APL.
Network Pharmacology-Based Validation of the Efficacy of Huiyangjiuji Decoction in the Treatment of Experimental Colitis
Authors: Yu Wei , Cheng Hongju , Zhu Baoliang , Yan Jing 
Published: May 2021

Ulcerative colitis (UC) is the major type of inflammatory bowel disease (IBD) characterized by an overactive immune responses and destruction of the colorectal epithelium with intricate pathological factors. In China, Huiyangjiuji decoction (HYJJ) has been widely administered against inflammation, but the underlying mechanical mechanisms are not known. A murine model of colitis was established by orally feeding 4% dextran sodium sulfate for 5 days. Intestinal organoids (IOs) were treated with TNFα (Tumor necrosis factor-α) as an ex-vivo UC model. A scratch assay combined with a co-culture system that incubated murine epithelial cell line (IEC-6) with macrophages (Mφs) was utilized to assess epithelial recovery under inflammatory conditions. Network pharmacology analysis was performed to elucidate the mechanism of HYJJ decoction. In the present study, we confirmed that HYJJ considerably alleviated of DSS-induced colitis, as evidenced by the improved intestinal injury and fecal albumin, as well as feces blood. Network pharmacology analysis identified the active components in HYJJ formula, and KEGG enrichment analysis indicated that HYJJ-target genes were enriched in pathogen-induced infections, cancer-related as well as inflammatory pathways. Consistently, RNA-sequencing demonstrated that HYJJ treated inhibited cytokine-cytokine interaction, IBD as well as TNF signaling pathways, confirming the anti-inflammatory and anti-neoplastic role of HYJJ decoction. In-vitro experimental evidence confirmed the suppression of pro-interleukins by HYJJ, including IL-2, IL-10 and IL-12. Moreover, the contribution of HYJJ to mucosal healing was corroborated by ex-vivo experiments, in which HYJJ rescued TNFα-compromised IOs functions, i.e., elevated mitochondrial stress (MOS) and impaired regeneration capacity. IEC-6 cells co-culture with Mφs from HYJJ-treated experimental colitis mice showed an improved migration capacity as compared to those incubated with Mφs from untreated colitis mice. We conclude that HYJJ re-establishes homeostasis of the gut epithelium during colitis by suppressing inflammation and orchestrating cytokines interaction.
Effects of Methanolic Extract Based-Gel From Saudi Pomegranate Peels With Enhanced Healing Potential on Excision Wounds in Diabetic Rats
Authors: Karim Shahid , Alkreathy Huda M. , Ahmad Aftab , Khan Mohammad Imran 
Published: May 2021

Introduction: Current study was designed to evaluate the wound healing activity of a Saudi pomegranate peel extract on excision wound healing in experimentally induced diabetes in rats.Methodology: Animals were divided into three groups: diabetic excision wound with no treatment, diabetic excision wound with gel alone and diabetic excision wound with Saudi pomegranate peel extract in gel. Animals were monitored for clinical signs, weekly body weight, morbidity and mortality during entire study period. The efficacy parameters evaluated were percent wound contraction, Hydroxyproline content, estimation of Transforming Growth Factor ß1 (TGF-ß1), Vascular Endothelial Growth Factor (VEGF), and Epidermal Growth Factor (EGF) in wound lysates by ELISA, mRNA expression of TGF-ß1, VEGF, and EGF in wound lysates by qPCR, Estimation of nitric oxide (NO) and NO synthase (NOS) in Wound Lysates and histopathology of skin for reepithelization, neovascularization, and inflammation.Results: The Saudi pomegranate peel extract in gel (5.0 g extract per 100 g gel) showed significant wound healing activity when compared to the vehicle control [p &lt; 0.05] following 21 days of treatment. Animals in the control and treatment groups were apparently normal through the study with no significant differences in body weights between groups. Expression of mRNA of TGFβ1, EGF and VEGF in wounds was the highest on day 14 post treatment 4.3, 3.5 and 0.9 fold higher respectively in the treatment group when compared to vehicle control, and on day 21, the values were 0.12, 0.3 and 0.83, respectively. No statistically significant differences were observed in TGF-ß1 levels in wounds on days 4, 7, 14 and 21 post treatment when compared to the vehicle control (p &gt; 0.05). Significantly higher levels of VEGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p &lt; 0.05). Significantly higher levels of EGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p &lt; 0.05). Mean hydroxyproline levels were higher in treatment group on days 4 and 7 when compared to vehicle control. NO levels in treatment group were significantly lower on days 7, 14 and 21 when compared to vehicle control (p &lt; 0.05). NOS activity in treatment group were significantly lower on days 4 and 7 when compared to vehicle control (p &lt; 0.05). Histopathological changes in skin wound in the treatment group were consistent with wound healing when compared to the vehicle group.Conclusion: This study’s findings suggest that topical application of SPPE gel effectively enhanced wound healing in experimentally induced diabetic conditions.
Does the Spatial Layout of a Playground Affect the Play Activities in Young Children? A Pilot Study
Authors: Sumiya Masashi , Nonaka Tetsushi 
Published: May 2021

BackgroundThe objective of this study was to describe, through measurement of physical activity and observation of free outdoor play, the relation between children’s free play and the spatial layout of the playground. To accomplish this, we altered the spatial layout of the same playground to see how the layout affects the play activity and the physical activity levels in the same children.MethodsParticipants were six young children (four girls and two boys; mean age = 5 years and 1 month, SD = 2.59 months). Participants’ physical activity level and the duration of different types of action that occurred in each area and their transitions were compared before and after the alteration of the play-equipment layout using the data from accelerometers and video recordings.ResultsA significant increase in physical activity occurred after the spatial layout alteration, which was related to action differences. Before the alteration, children tended to play in a similar manner for a given play area; however, after the alteration, pronounced interindividual variation in play activity across children was observed.ConclusionThe present pilot study found that in free play situations in the outdoor playground, the spatial layout of playground affects the pattern of play activity and the physical activity levels of young children.
Hope and Distress Are Not Associated With the Brain Tumor Stage
Authors: Mayer Simone , Fuchs Stefanie , Fink Madeleine , Schäffeler Norbert , Zipfel Stephan , Geiser Franziska , Reichmann Heinz , Falkenburger Björn , Skardelly Marco , Teufel Martin 
Published: May 2021

ObjectiveHopelessness and depression are strongly associated with suicidality. Given that physical and psychological outcomes can be altered with hope, hope is a therapeutic goal of increasing importance in the treatment of brain tumor patients. Moreover, it is not yet understood which factors affect the perception of hope in brain tumor patients. In addition, it remains uncertain whether lower-grade brain tumor patients suffer less from psycho-oncological distress than higher-grade brain tumor patients.MethodsNeuro-oncological patients were examined perioperatively with the Distress Thermometer (DT) and the Herth Hope Index (HHI). In addition, psychological comorbidities (anxiety GAD-2, depression PHQ-2) and an assessment of general psycho-oncological distress were recorded.ResultsSixty-six brain tumor patients were included (median age 53 years, 35% higher-grade brain tumors, i.e., WHO grade III/IV). No differences between higher- and lower-grade brain tumor patients were observed for general psycho-oncological distress and hope. However, higher-grade brain tumor patients showed a significantly higher level of depression (p ≤ 0.001) and more negative expectations regarding therapeutic success (H = 4.873, p ≤ 0.050). The extent of depression correlated negatively with hope.ConclusionUnexpectedly, higher-grade brain tumor patients remained as hopeful as lower-grade brain tumor patients despite the devastating diagnosis, higher levels of depression, and a worse expectation of therapeutic success. Conversely, lower-grade brain tumor patients experience as much psycho-oncological distress as patients with a higher-grade brain tumor, underpinning the imperative need for comprehensive psycho-oncological screening. For all brain tumor patients, considering hope is important to avoid suicides resulting from hopelessness and depression.
Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment
Authors: Reponen Elina J. , Tesli Martin , Dieset Ingrid , Steen Nils Eiel , Vedal Trude S. J. , Szabo Attila , Werner Maren C. F. , Lunding Synve H. , Johansen Ingrid T. , Rødevand Linn N. , Andreassen Ole A. , Ueland Thor 
Published: May 2021

Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors.Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses.Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors.Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime.
Acupuncture as an Independent or Adjuvant Management to Standard Care for Perimenopausal Depression: A Systematic Review and Meta-Analysis
Authors: Zhao Fei-Yi , Fu Qiang-Qiang , Kennedy Gerard A. , Conduit Russell , Zhang Wen-Jing , Zheng Zhen 
Published: May 2021

Background: Many women with perimenopausal depression (PMD) have sought alternative therapies such as acupuncture because of concerns about risks associated with antidepressant and hormone replacement therapy (HRT). This systematic review aimed to clarify if acupuncture is effective for PMD compared with waitlist control or placebo/sham acupuncture, and if acupuncture alone or combined with standard care (antidepressant and/or HRT) is more effective in ameliorating PMD in comparison with standard care alone.Methods: Randomized controlled trials (RCTs) of PMD treatment via acupuncture vs. waitlist control or placebo/sham acupuncture, and RCTs of PMD treatment via acupuncture alone or combined with Western pharmacotherapy vs. Western pharmacotherapy were searched for from seven databases from inception to December 2020. Cochrane criteria were followed.Results: Twenty-five studies involving 2,213 women were analyzed. Meta-analyses indicated that acupuncture significantly reduced the global scores of Hamilton Depression Scale (HAMD) [standardized mean difference (SMD) = −0.54, 95% CI (−0.91, −0.16), p &lt; 0.01], compared with standard care. The therapeutic effect of acupuncture maintained at 2-, 4-, and 12-week follow-ups. Acupuncture combined with standard care was more effective than standard care alone in decreasing HAMD scores [SMD = −0.82, 95% CI (−1.07, −0.58), p &lt; 0.01]. Too few RCTs were available to assess the clinical efficacy differences between acupuncture and placebo/sham acupuncture or HRT alone. Acupuncture also showed better effects in decreasing Kupperman index (KI) scores, whether compared with antidepressant alone [MD = −4.55, 95% CI (−8.46, −0.65), p = 0.02] or antidepressant combined with HRT [MD = −0.89, 95% CI (−1.34, −0.43), p &lt; 0.01].Conclusions: In comparison with standard care, acupuncture alone or combined with standard care was associated with significant improvements in PMD and reductions of other menopausal symptoms. This finding suggests that acupuncture may be a useful addition to treatment for PMD.
Self-medication practice and associated factors among adults in Wolaita Soddo town, Southern Ethiopia
Authors: Mathewos Tamirat , Daka Kassa , Bitew Shimelis , Daka Deresse 
Published: May 2021

Background: Self-medication is the selection and use of medicines by individuals to treat their self-recognized illnesses or symptoms. Self-medication can decrease costs and enable health professionals to concentrate on more serious health problems.
Aim: To assess self-medication practice and associated factors among adults in Wolaita Soddo town, Southern Ethiopia, 2017.
Methods: An institution-based cross-sectional study was conducted from September 30 to October 30, 2017. A multi-stage sampling technique of drug retail outlets in Wolaita Soddo town was employed to identify 623 individuals that came to buy drugs in the past three months. Data was collected using a structured questionnaire.
Results: About 33.7% of the respondents had practiced self-medication in the past 3 months. Multivariate analysis revealed that female sex (adjusted odds ratio (AOR) = 2.22, 95% confidence interval (CI): 1.47–3.36), low income (AOR = 3.95, 95% CI: 2.32–6.73) and higher educational level (AOR = 5.79, 95% CI: 2.47–13.58) were the independent factors significantly affecting the practice of self-medication with drugs. Headache/fever (32.4%), respiratory tract infections (31.4%) and gastrointestinal diseases (16.2%) were the most frequently reported illnesses or symptoms of illnesses that prompted self-medication of study participants.
Conclusion: Health education campaigns, strict legislations on dispensing drugs from private pharmacies, and improving accessibility and affordability of health care are among the important interventions required to change people’s health-seeking behavior and prevent the potential risks of self-medication.
Comprehensive Assessment of Fluid Status by Point-of-Care Ultrasonography
Authors: Argaiz Eduardo R. , Koratala Abhilash , Reisinger Nathaniel 
Published: May 2021

Abstract
The management of complex fluid and electrolyte disorders is central to the practice of nephrologists. The sensitivity of physical examination alone to determine fluid status is limited, precluding accurate clinical decision making. Point-of-care ultrasonography (POCUS) is emerging as a valuable, noninvasive, bedside diagnostic tool for objective evaluation of physiologic and hemodynamic parameters related to fluid status, tolerance, and responsiveness. Rapid bedside sonographic evaluation can obtain qualitative data on cardiac function and quantitative data on pulmonary congestion. Advanced POCUS, including goal-directed Doppler echocardiography, provides additional quantitative information, including flow velocities and pressures across the cardiac structures. Recently, abnormal Doppler flow patterns in abdominal organs secondary to increased right atrial pressure have been linked to congestive organ damage, adding another component to the hemodynamic assessment. Integrating POCUS findings with clinical and laboratory data can further elucidate a patient’s hemodynamic status. This drives decisions regarding crystalloid administration or, conversely, diuresis or ultrafiltration and allows tailored therapy for individual patients. In this article, we provide an overview of the focused assessment of cardiovascular function and pulmonary and venous congestion using POCUS and review relevant literature.