bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nationwide analysis of treatment outcomes in children and adolescents routinely treated for tuberculosis in the Netherlands
Authors: Gafar Fajri , van't Boveneind-Vrubleuskaya Natasha , Akkerman Onno W. , Wilffert Bob , Alffenaar Jan-Willem C. 
Published: September 2019

BackgroundAs a vulnerable population, children and adolescents with tuberculosis (TB) are faced with many challenges, even those who live in low TB incidence countries. We aimed to evaluate factors associated with TB treatment outcomes allowing more focused interventions to support this population once diagnosed.MethodsA retrospective cohort study using a nationwide surveillance database was performed in children and adolescents (aged 0–18 years) treated for TB in the Netherlands from 1993 to 2018. Logistic regression analyses were used to estimate adjusted odds ratios (aOR) for associated factors of mortality and loss to follow-up (LTFU).ResultsAmong 3253 eligible patients with known outcomes, 94.4% (95.9% children and 92.8% adolescents) were cured or completed treatment, 0.7% died during treatment and 4.9% were LTFU. There were no reported treatment failures. Risk factors of death included children aged 2–4 years (aOR 10.42), central nervous system TB (aOR 5.14), miliary TB (aOR 10.25), HIV co-infection (aOR 8.60), re-treated TB cases (aOR 10.12) and drug-induced liver injury (aOR 6.50). Active case-finding was a protective factor of death (aOR 0.13). Risk factors of LTFU were adolescents aged 15–18 years (aOR 1.91), illegal immigrants (aOR 4.28), urban domicile (aOR 1.59), unknown history of TB contact (aOR 1.99), drug-resistant TB (aOR 2.31), single adverse drug reaction (aOR 2.12), multiple adverse drug reactions (aOR 7.84) and treatment interruption >14 days (aOR 6.93). Treatment in recent years (aOR 0.94) and supervision by public health nurses (aOR 0.14) were protective factors of LTFU.ConclusionHighly successful treatment outcomes were demonstrated in children and adolescents routinely treated for TB. Special attention should be given to specific risk groups to improve treatment outcomes.
Genome-wide analysis of AGO, DCL and RDR gene families reveals RNA-directed DNA methylation is involved in fruit abscission in Citrus sinensis
Authors: Sabbione Agustín , Daurelio Lucas , Vegetti Abelardo , Talón Manuel , Tadeo Francisco , Dotto Marcela 
Published: September 2019

Abstract

Background
Small RNAs regulate a wide variety of processes in plants, from organ development to both biotic and abiotic stress response. Being master regulators in genetic networks, their biogenesis and action is a fundamental aspect to characterize in order to understand plant growth and development. Three main gene families are critical components of RNA silencing: DICER-LIKE (DCL), ARGONAUTE (AGO) and RNA-DEPENDENT RNA POLYMERASE (RDR). Even though they have been characterized in other plant species, there is no information about these gene families in Citrus sinensis, one of the most important fruit species from both economical and nutritional reasons. While small RNAs have been implicated in the regulation of multiple aspects of plant growth and development, their role in the abscission process has not been characterized yet.

Results
Using genome-wide analysis and a phylogenetic approach, we identified a total of 13 AGO, 5 DCL and 7 RDR genes. We characterized their expression patterns in root, leaf, flesh, peel and embryo samples using RNA-seq data. Moreover, we studied their role in fruit abscission through gene expression analysis in fruit rind compared to abscission zone from samples obtained by laser capture microdissection. Interestingly, we determined that the expression of several RNA silencing factors are down-regulated in fruit abscission zone, being particularly represented gene components of the RNA-dependent DNA Methylation pathway, indicating that repression of this process is necessary for fruit abscission to take place in Citrus sinensis.

Conclusions
The members of these 3 families present characteristic conserved domains and distinct expression patterns. We provide a detailed analysis of the members of these families and improved the annotation of some of these genes based on RNA-seq data. Our data suggests that the RNA-dependent DNA Methylation pathway is involved in the important fruit abscission process in C. sinensis.
Increased liver echogenicity and liver enzymes are associated with extreme obesity, adolescent age and male gender: analysis from the German/Austrian/Swiss obesity registry APV
Authors:   on behalf of the APV-Study Group, Greber-Platzer Susanne , Thajer Alexandra , Bohn Svenja , Brunert Annette , Boerner Felicitas , Siegfried Wolfgang , Artlich Andreas , Moeckel Anja , Waldecker-Krebs Hildegunde , Pauer Sophie , Holl Reinhard W. 
Published: September 2019

Abstract

Background
Childhood obesity is often associated with non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in pediatrics.

Methods
This multi-center study analyzed liver echogenicity and liver enzymes in relation to obesity, age, gender and comorbidities. Data were collected using a standardized documentation software (APV) from 1.033 pediatric patients (age: 4–18 years, body mass index = BMI: 28–36 kg/m2, 50% boys) with overweight (BMI >90th percentile), obesity (BMI >97th percentile) or extreme obesity (BMI > 99.5th percentile) and obesity related comorbidities, especially NAFLD from 26 centers of Germany, Austria and Switzerland. Liver enzymes aspartate aminotransferase (AST), alanine-aminotransferase (ALT) and gamma glutamyltransferase (gammaGT) were evaluated using 2 cut-off values a) > 25 U/L and b) > 50 U/L. Multiple logistic regression models were used for statistical analysis.

Results
In total, 44% of the patients showed increased liver echogenicity. Liver enzymes > 25 U/L were present in 64% and > 50 U/L in 17%. Increased liver echogenicity was associated with elevated liver enzymes (> 25 U/L: odds ratio (OR) = 1.4, 95% CI: 1.1–1.9, P < 0.02; > 50 U/L: OR = 3.5, 95% CI: 2.4–5.1, P < 0.0001). Extreme obesity, adolescence and male gender were associated with increased liver echogenicity (extreme obesity vs overweight OR = 3.5, 95% CI: 1.9–6.1, P < 0.0001; age > 14 years vs age < 9 years OR = 2.2, 95% CI: 1.4–3.5, P < 0.001; boys vs girls OR = 1.6, 95% CI: 1.2–2.0, P < 0.001) and elevated liver enzymes (extreme obesity vs overweight > 25 U/L: OR = 4.1, 95% CI: 2.4–6.9, P < 0.0001; > 50 U/L: OR = 18.5, 95% CI: 2.5–135, P < 0.0001; age > 14 years vs age < 9 years > 50 U/L: OR = 1.9, 95% CI: 1.0–3.7, P > 0.05; boys vs girls > 25 U/L: OR = 3.1, 95% CI: 2.4–4.1, P < 0.0001; > 50 U/L: OR = 2.1, 95% CI: 1.5–2.9, P < 0.0001). Impaired glucose metabolism showed a significant correlation with elevated liver enzymes > 50 U/L (OR = 4.4, 95% CI: 1.6–11.8, P < 0.005). Arterial hypertension seemed to occur in patients with elevated liver enzymes > 25 U/L (OR 1.6, 95% CI: 1.2–2.0, P < 0.005).

Conclusions
NAFLD is strongly related to extreme obesity in male adolescents. Moreover impaired glucose tolerance was observed in patients with elevated liver enzymes > 50 U/L, but arterial hypertension was only present in patients with moderately elevated liver enzymes > 25 U/L.
Mediators of gender effects on depression among cardiovascular disease patients in Palestine
Authors: Allabadi Hala , Probst-Hensch Nicole , Alkaiyat Abdulsalam , Haj-Yahia Saleem , Schindler Christian , Kwiatkowski Marek , Zemp Elisabeth 
Published: September 2019

AbstractBackgroundAmong patients suffering from coronary heart disease (CHD) and comorbid depression, women experience a higher burden compared to men. Little is known on the characteristics that differentiate men and women with both diseases and whether these factors mediate gender effects on depression. This study assessed whether women are more likely to suffer from depression and which characteristics mediate gender effects on depression among a cardiac population in Palestine, specifically addressing the role of post-traumatic stress disorder (PTSD).MethodsUsing a cross-sectional design, patients consecutively admitted with a CHD to one of the four main hospitals in Nablus, Palestine, were interviewed using a structured questionnaire with validated instruments. Data was also obtained from hospital medical records. Patients were assessed for depression using the Cardiac Depression Scale (CDS). Bivariate analysis was conducted to compare characteristics of women and men with and without depressive symptoms. Mediators (direct and indirect effects) of the association between gender and depression were evaluated using a structural equation model (SEM).ResultsWomen were more likely to suffer from severe depression than men (28.7% vs. 18.8%). Female gender was positively associated with higher PTSD symptoms, comorbidities, somatic symptoms and income, and with lower resilience, self-esteem, quality of life, education, prevalence of smoking and physical activity. Structural equation modeling revealed negative indirect effects of gender on depression (CDS score) through resilience, self-esteem and physical activity, whereas positive indirect effects of gender on depression were observed through PTSD, comorbidities, somatic symptoms and smoking. There was no direct effect of gender on depression.ConclusionThis study found a higher prevalence of severe depression in female patients with cardiac disease compared to male cardiac patients. Our findings provide novel information on mediating factors of the association between gender and depression among cardiac patients, in particular PTSD. The results emphasize the need for further research on potential mediating factors that could account for gender differences in depression and the need to provide support programs for female patients with comorbid CHD and depression to improve their psycho-social well-being.
Is the 2013 American Thoracic Society CPAP-tracking system algorithm useful for managing non-adherence in long-term CPAP-treated patients?
Authors: Rotty Marie-Caroline , Mallet Jean-Pierre , Suehs Carey M. , Martinez Christian , Borel Jean-Christian , Rabec Claudio , Bourdin Arnaud , Molinari Nicolas , Jaffuel Dany 
Published: September 2019

Abstract

Background
Whereas telemedicine usage is growing, the only clinical algorithm for Continuous Positive Airway Pressure (CPAP) adherence management is that stipulated by the 2013 American Thoracic Society (ATS). The capacity of the latter to predict non-adherence in long-term CPAP-treated patients has not been validated.

Methods
Patients from the prospective real-life InterfaceVent study (NCT03013283, study conducted in an adult cohort undergoing at least 3 months of CPAP) and eligible for ATS algorithm usage were analysed. The residual device Apnea–Hypopnea-Index (AHIflow) and High Large Leak (HLL) thresholds proposed in the ATS algorithm were evaluated for predicting adherence (i.e. AHIflow > 10/h, HLLs 95th > 24 L/min for ResMed® devices and ResMed® nasal mask, HLLs 95th > 36 l/min for ResMed® devices and ResMed® oronasal masks, HLLs > 1 h for Philips® devices and HHLs > 60 l/min for Fisher & Paykel® devices). Adherence was defined according to the 2013 ATS algorithm (i.e. CPAP use > 4 h/j for at least 70% of days).

Results
650/1484 patients eligible for ATS algorithm usage were analysed (15.38% non-adherent, 74% male with a median (IQ25–75) age of 68 (61–77) years, a body mass index of 30.8 (27.7–34.5) kg/m2, an initial AHI of 39 (31–55) events/h, and CPAP-treatment-duration of 5.1 (2.2–7.8) years). Logistic regression analysis demonstrated no significant relationship between the ATS proposed AHIflow or HLL thresholds and non-adherence. Complementary ROC curve analysis failed to determine satisfactory AHIflow and HLL thresholds.

Conclusion
When managing non-adherence in long-term CPAP-treated patients, our data do not validate absolute AHIflow or HLL thresholds in general.

Trial registration
The INTERFACE-VENT study is registered on ClinicalTrials.gov (Identifier: study (NCT03013283).
Surgical approach to solid pseudopapillary neoplasms of the proximal pancreas: minimally invasive vs. open
Authors: Hao Emmanuel II Uy , Rho Seoung Yoon , Hwang Ho Kyoung , Chung Jae Uk , Lee Woo Jung , Yoon Dong Sup , Kang Chang Moo 
Published: September 2019

Abstract

Background
Solid pseudopapillary neoplasms (SPN) of the pancreas are rare pancreatic neoplasms where complete resection is the cornerstone in management. It has been demonstrated in previous studies that minimally invasive surgical approaches are effective management options in treating SPNs of the distal pancreas. The purpose of this study is to evaluate the feasibility of minimally invasive surgery in treating SPNs of the uncinate, head, and neck of the pancreas.

Methods
Data from 2005 to 2017 at Severance Hospital of the Yonsei University Health systems in Seoul, South Korea, were retrospectively collected for 25 patients who were diagnosed with SPN of the uncinate, head, and neck of the pancreas and who underwent curative resection. Three groups of patients were considered, depending on the year of surgery, in order to determine trends in the surgical management of SPN. The patients were also divided into two groups corresponding to the type of operation done (minimally invasive surgery vs. open surgery). Perioperative patient data, including age, gender, body mass index (BMI), tumor size, and operation done, were compared and analyzed statistically. Long-term nutritional effects were measured using the Controlling Nutritional Status (CONUT) scoring system.

Results
There were no statistically significant differences in age, gender, BMI, symptomatic presentation, operation type, tumor size, and tumor stage between the three time periods. In comparing between minimally invasive and open surgery, there were no statistically significant differences in age, gender, symptomatic presentation, BMI, tumor size, preoperative stage, type of operation, operation time, pancreatic duct size, post-operative pancreatic fistula (POPF) grade, death associated with disease, recurrence, pathological parameters, and change in CONUT score. There was a significant difference in tumor size (4.5 ± 1.8 vs. 2.6 ± 1.0 cm, p = 0.004), blood loss (664.2 ± 512.4 vs. 277.7 ± 250.8 mL, p = 0.024), need to transfuse (33% vs. 0%, p = 0.023), hospital length of stay (27.4 ± 15.3 vs. 11.5 ± 5.3 days, p = 0.002), and complication rate (75% vs. 30.8%, p = 0.027) between the two groups.

Conclusions
In appropriately selected patients with SPNs of the uncinate, head, and neck of the pancreas, a minimally invasive surgical approach offers at least equal oncologic and nutritional outcomes, while demonstrating decreased complications and decreased hospital length of stay compared with that of an open surgical approach.
The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance
Authors: Song Wei , Sharan Roded , Ovcharenko Ivan 
Published: September 2019

Abstract

Background
Robustness and evolutionary stability of gene expression in the human genome are established by an array of redundant enhancers.

Results
Using Hi-C data in multiple cell lines, we report a comprehensive map of promoters and active enhancers connected by chromatin contacts, spanning 9000 enhancer chains in 4 human cell lines associated with 2600 human genes. We find that the first enhancer in a chain that directly contacts the target promoter is commonly located at a greater genomic distance from the promoter than the second enhancer in a chain, 96 kb vs. 45 kb, respectively. The first enhancer also features higher similarity to the promoter in terms of tissue specificity and higher enrichment of loop factors, suggestive of a stable primary contact with the promoter. In contrast, a chain of enhancers which connects to the target promoter through a neutral DNA segment instead of an enhancer is associated with a significant decrease in target gene expression, suggesting an important role of the first enhancer in initiating transcription using the target promoter and bridging the promoter with other regulatory elements in the locus.

Conclusions
The widespread chained structure of gene enhancers in humans reveals that the primary, critical enhancer is distal, commonly located further away than other enhancers. This first, distal enhancer establishes contacts with multiple regulatory elements and safeguards a complex regulatory program of its target gene.
Peripheral sensory neurons govern development of the nervous system in bivalve larvae
Authors: Yurchenko Olga V. , Savelieva Anna V. , Kolotuchina Natalia K. , Voronezhskaya Elena E. , Dyachuk Vyacheslav A. 
Published: September 2019

AbstractRecent findings regarding early lophotrochozoan development have altered the conventional model of neurogenesis and revealed that peripheral sensory elements play a key role in the initial organization of the larval nervous system. Here, we describe the main neurogenetic events in bivalve mollusks in comparison with other Lophotrochozoa, emphasizing a novel role for early neurons in establishing larval nervous systems and speculating about the morphogenetic function of the apical organ. We demonstrate that during bivalve development, peripheral sensory neurons utilizing various transmitters differentiate before the apical organ emerges. The first neurons and their neurites serve as a scaffold for the development of the nervous system. During veliger stage, cerebral, pleural, and visceral ganglia form along the lateral (visceral) nerve cords in anterior-to-posterior axis. The pedal ganglia and corresponding ventral (pedal) nerve cords develop much later, after larval settlement and metamorphosis. Pharmacological abolishment of the serotonin gradient within the larval body disrupts the navigation of “pioneer” axons resulting in malformation of the whole nervous system architecture. Comparative morphological data on neurogenetic events in bivalve mollusks shed new light on the origin of the nervous system, mechanisms of early axon navigation, and sequence of the tetraneurous nervous system formation. Furthermore, this information improves our understanding of the basic nervous system architecture in larval Bivalvia and Mollusca.
Evidence-based preschool-age vision screening: health policy considerations
Authors: Zimmerman Deena Rachel , Ben-Eli Hadas , Moore Bruce , Toledano Monique , Stein-Zamir Chen , Gordon-Shaag Ariela 
Published: September 2019

AbstractBackgroundThere are many causes of visual impairment, and even blindness, which are treatable or at least preventable. Two such conditions are strabismus (crossed-eye, squint) and refractive error (visual image not focused on the most sensitive part of the retina). If these are not detected and corrected at an early age, they can lead to an irreversible impairment known as amblyopia (lazy eye). Pediatric vision screening and subsequent treatment for amblyopia and amblyogenic risk factors are thus key to preventing vision loss. Furthermore, vision screening can detect moderate to high hyperopia, which has been found to be associated with poor school readiness.Evidence-based recommendations call for screening children at 3–5 years of age; they are old enough to cooperate, but still within the window of effective intervention. However, these recommendations have yet to be universally implemented as the standard of care.MethodsThis paper integrates a review of the literature and the international experience of preschool vision screening with the findings from a preliminary feasibility study of expanded screening in Israel to formulate a discussion of the current health policy challenge in Israel and the options for addressing it. The advantages and disadvantages of various venues for vision screening are discussed.FindingsScreening by optometrists in Mother and Child Health Centers, as implemented in a recent pilot project in the Jerusalem District, would allow the most comprehensive testing. Photo-screening in preschools would reach the most children, but at the cost of missing hyperopia (farsightedness). Either approach would probably constitute improvements over the current situation. The relative strengths of the two approaches depends in part on the ability to purchase automatic screening equipment (and the efficacy of that equipment) vs. the ongoing cost of paying trained personnel.ConclusionsFurther research should be conducted in Israel to determine the prevalence of refractive errors, so that best practices can be established for Israel’s population and social needs. In the interim, the Ministry of Health should promptly implement the inclusion of preschool visions screening for children in the approved “basket of services” covered by the National Health Insurance Laws, using photo-screening, including collection of the clinical data.
Hepatocellular carcinoma with a direct right atrial extension in an HCV patient previously treated with direct-acting antiviral therapy: a case report
Authors: Abdelnabi Mahmoud , Almaghraby Abdallah , Saleh Yehia , Abd Elsamad Sherif 
Published: September 2019

Abstract

Background
Hepatocellular carcinoma (HCC) is considered the third-leading cause of cancer-related mortality worldwide. Most cases of HCC are usually associated with liver cirrhosis due to various causes such as alcohol or more commonly viral hepatitis. Usually, patients remain asymptomatic for a long time, and symptoms are usually related to the cirrhosis itself or secondary to tumor extension. Intra-cardiac involvement with HCC rarely develops with a very poor prognosis. The occurrence and recurrence of HCC in cirrhotic patients treated with direct-acting antiviral (DAA) therapy (sofosbuvir) have been discussed in a few trials so far with no valid answer.

Case presentation
We are reporting a case of recurrent HCC with an accidentally discovered direct right atrial extension with tumor thrombus through the inferior vena cava (IVC) in a cirrhotic patient previously treated with DAA. Unfortunately, due to his critical general condition, he died within days.

Conclusion
Cardiac involvement in HCC rarely occurs and usually develops in advanced stages of HCC with very poor reported prognosis. Data regarding the relation between DAA and HCC development is controversial.
Assessment of apparent diffusion coefficient value as prognostic factor for renal cell carcinoma aggressiveness
Authors: Mohammad Ahmad Medhat Ibraheem , Sabr Mohammad , Roshy Eman 
Published: September 2019

Abstract

Background
Assurance of prognostic elements is important for the management of renal cell carcinoma (RCC). Our goal was to check the relation between apparent diffusion coefficient (ADC) values and parameters predicting prognosis of RCC. Fifty pathologically confirmed RCC underwent diffusion-weighted (DW) MRI. ADC values were calculated using b factor (800 s/mm2). The correlation between ADC values and tumor size, cystic/necrotic feature, growth pattern, unenhanced T1, histological grade, clinical stage, and distant metastasis were analyzed.

Results
The optimal ADC threshold for prognosis of RCC appeared to be 1.4 × 10−3 mm2/s. There was a significant inverse correlation between ADC values and growth pattern (R = − 0, P = 0.05), unenhanced T1(R = − 0.41, P = 0.01), cystic/necrotic feature (R = − 0.4, P = 0.01), histological grade (R = − 0.37, P = 0.02), clinical stage (r = − 0.4, P = 0.01), and distant metastasis (R = − 0.33, P = 0.04), and significant linear correlation with tumor size (R = 0.39, P < 0.02).

Conclusion
The performance of ADC value as a newly proposed prognostic parameter follows with the degree of tumor differentiation and that may recognize extremely aggressive RCC. RCC with low ADC values should be inspected extensively for the risk of high pathological grade, high clinical stage, and distant metastasis.