bluuebunny/crossref_metadata_2025 huggingface dataset:
Trust motivation: The self-regulatory processes underlying trust decisions
Authors: van der Werff Lisa , Legood Alison , Buckley Finian , Weibel Antoinette , de Cremer David
Published: September 2019

Theorizing about trust has focused predominantly on cognitive trust cues such as trustworthiness, portraying the trustor as a relatively passive observer reacting to the attributes of the other party. Using self-determination and control theories of motivation, we propose a model of trust motivation that explores the intraindividual processes involved in the volitional aspects of trust decision-making implied by the definition of trust as a willingness to be vulnerable. We distinguish between intrinsic and extrinsic drivers of trust and propose a two-phase model of trust goal setting and trust regulation. Our model offers a dynamic view of the trusting process and a framework for understanding how trust cognition, affect and behavior interact over time. Furthermore, we discuss how trust goals may be altered or abandoned via a feedback loop during the trust regulation process. We conclude with a discussion of potential implications for existing theory and future research.
Preparation of Direct Healthcare Professional Communication: An Exploratory Study on the Experiences and Perceptions of European Pharmaceutical Companies and the EMA
Authors: Boskovic Arnela , Møllebæk Mathias , Kaae Susanne
Published: September 2019

Background:

Despite the regulatory requirement for cooperation between marketing authorization holders (MAHs) and European Medicines Agency (EMA) in the direct healthcare professional communication (DHPC) preparation, no literature has explored DHPCs from an industry-regulator perspective. This constitutes a significant knowledge gap as any possibility of improving current DHPC effectiveness depends on decisions in the cooperative preparation phase. Thus, this EU-centered study explores differences in perceptions and experiences of DHPCs of European MAHs and EMA.

Methods:

European MAHs (n = 6) and EMA representatives (n = 2) were interviewed. The verbatim transcripts were coded into themes using NVivo software. Interview analysis was performed following a phenomenological approach of meaning condensation.

Results:

The DHPC process was perceived as burdensome by the industry. One company stated the process was time-consuming either due to EMA’s internal lengthy approval process or the translation activities with local company affiliates and national competent authorities. Three companies stated that DHPCs were not effective. One company stated that DHPCs are sent out due to legal obligations and not because of their use as a risk minimization measure (RMM). Newly emerged safety concerns were found difficult to phrase. Optimization proposals included improved timelines, scrutinization of healthcare professionals and better communication tools in clinical practice.

Conclusion:

DHPCs were not perceived as optimal, although the most effective intervention as it targets healthcare professionals directly. Continuous evaluation by EMA of DHPCs and evaluation on how to reach healthcare professionals are necessary. It is believed that industry perceptions from this study can support EMA with improved regulatory decision making to benefit public health.
Challenging Evolution in Public Schools: Race, Religion, and Attitudes toward Teaching Creationism
Authors: Salazar Esmeralda Sánchez , Vaidyanathan Brandon , Ecklund Elaine Howard , Garcia Adriana
Published: September 2019

Researchers argue that white evangelical Christians are likely to support teaching creationism in public schools. Yet, less is known about the role religion may play in shaping attitudes toward evolution and teaching creationism among blacks and Latinos, who are overrepresented in U.S. conservative Protestant traditions. This study fills a gap in the literature by examining whether religious factors (e.g., religious affiliation and Biblical literalism) relate to differences in support for teaching creationism between blacks and Latinos compared to whites and other racial groups. Using a nationally representative survey (N = 9,425), we find that although black and Latino Americans support teaching creationism more than other groups, religion plays a stronger role among blacks in shaping support for teaching creationism instead of evolution. Results add an important racial dimension to scholarly discussions on religion and science and suggest further exploration of race alongside other factors that may contribute to support for teaching creationism.
Patients with spontaneous remission of high-risk MDS and AML show persistent preleukemic clonal hematopoiesis
Authors: Grunwald Victoria V. , Hentrich Marcus , Schiel Xaver , Dufour Annika , Schneider Stephanie , Neusser Michaela , Subklewe Marion , Fiegl Michael , Hiddemann Wolfgang , Spiekermann Karsten , Rothenberg-Thurley Maja , Metzeler Klaus H.
Published: September 2019

Key Points

We report longitudinal mutational analyses of 2 patients with high-risk MDS and AML experiencing spontaneous disease remissions. Both patients had persistent clonal hematopoiesis during remission, harboring all but 1 of the mutations from the initial diagnostic sample.
Nongenotoxic antibody-drug conjugate conditioning enables safe and effective platelet gene therapy of hemophilia A mice
Authors: Gao Chunyan , Schroeder Jocelyn A. , Xue Feng , Jing Weiqing , Cai Yuanhua , Scheck Amelia , Subramaniam Saravanan , Rao Sridhar , Weiler Hartmut , Czechowicz Agnieszka , Shi Qizhen
Published: September 2019

Key Points

Hematopoietic cell–targeted antibody-drug conjugate preconditioning is highly effective for platelet gene therapy in hemophilia A mice. Platelet-specific FVIII gene therapy can effectively prevent a needle-induced knee joint injury in hemophilia A mice.
Defining severe obstructive lung disease in the biologic era: an endotype-based approach
Authors: Martin Richard J. , Bel Elisabeth H. , Pavord Ian D. , Price David , Reddel Helen K.
Published: September 2019

Severe obstructive lung disease, which encompasses asthma, chronic obstructive pulmonary disease (COPD) or features of both, remains a considerable global health problem and burden on healthcare resources. However, the clinical definitions of severe asthma and COPD do not reflect the heterogeneity within these diagnoses or the potential for overlap between them, which may lead to inappropriate treatment decisions. Furthermore, most studies exclude patients with diagnoses of both asthma and COPD. Clinical definitions can influence clinical trial design and are both influenced by, and influence, regulatory indications and treatment recommendations. Therefore, to ensure its relevance in the era of targeted biologic therapies, the definition of severe obstructive lung disease must be updated so that it includes all patients who could benefit from novel treatments and for whom associated costs are justified. Here, we review evolving clinical definitions of severe obstructive lung disease and evaluate how these have influenced trial design by summarising eligibility criteria and primary outcomes of phase III randomised controlled trials of biologic therapies. Based on our findings, we discuss the advantages of a phenotype- and endotype-based approach to select appropriate populations for future trials that may influence regulatory approvals and clinical practice, allowing targeted biologic therapies to benefit a greater proportion and range of patients. This calls for co-ordinated efforts between investigators, pharmaceutical developers and regulators to ensure biologic therapies reach their full potential in the management of severe obstructive lung disease.
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

Background

As 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.

Methods

A 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).

Results

Among 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.

Conclusion

Highly 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

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

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

Background

Among 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).

Methods

Using 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).

Results

Women 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.

Conclusion

This 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

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

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

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

Recent 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

Background

There 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.

Methods

This 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.

Findings

Screening 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.

Conclusions

Further 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

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

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.
Development of an Adrenocortical Cancer Humanized Mouse Model to Characterize Anti-PD1 Effects on Tumor Microenvironment
Authors: Lang Julie , Capasso Anna , Jordan Kimberly R , French Jena D , Kar Adwitiya , Bagby Stacey M , Barbee Jacob , Yacob Betelehem W , Head Lia S , Tompkins Kenneth D , Freed Brian M , Somerset Hilary , Clark Toshimasa J , Pitts Todd M , Messersmith Wells A , Eckhardt S Gail , Wierman Margaret E , Leong Stephen , Kiseljak-Vassiliades Katja
Published: September 2019

Context

Although the development of immune checkpoint inhibitors has transformed treatment strategies of several human malignancies, research models to study immunotherapy in adrenocortical carcinoma (ACC) are lacking.

Objective

To explore the effect of anti-PD1 immunotherapy on the alteration of the immune milieu in ACC in a newly generated preclinical model and correlate with the response of the matched patient.

Design, Setting, and Intervention

To characterize the CU-ACC2-M2B patient-derived xenograft in a humanized mouse model, evaluate the effect of a PD-1 inhibitor therapy, and compare it with the CU-ACC2 patient with metastatic disease.

Results

Characterization of the CU-ACC2-humanized cord blood-BALB/c-Rag2nullIl2rγnullSirpaNOD model confirmed ACC origin and match with the original human tumor. Treatment of the mice with pembrolizumab demonstrated significant tumor growth inhibition (60%) compared with controls, which correlated with increased tumor infiltrating lymphocyte activity, with an increase of human CD8+ T cells (P < 0.05), HLA-DR+ T cells (P < 0.05) as well as Granzyme B+ CD8+ T cells (<0.001). In parallel, treatment of the CU-ACC2 patient, who had progressive disease, demonstrated a partial response with 79% to 100% reduction in the size of target lesions, and no new sites of metastasis. Pretreatment analysis of the patient's metastatic liver lesion demonstrated abundant intratumoral CD8+ T cells by immunohistochemistry.

Conclusions

Our study reports the first humanized ACC patient-derived xenograft mouse model, which may be useful to define mechanisms and biomarkers of response and resistance to immune-based therapies, to ultimately provide more personalized care for patients with ACC.
Obesity, Neuroinflammation, and Reproductive Function
Authors: Lainez Nancy M , Coss Djurdjica
Published: September 2019

The increasing occurrence of obesity has become a significant public health concern. Individuals with obesity have higher prevalence of heart disease, stroke, osteoarthritis, diabetes, and reproductive disorders. Reproductive problems include menstrual irregularities, pregnancy complications, and infertility due to anovulation, in women, and lower testosterone and diminished sperm count, in men. In particular, women with obesity have reduced levels of both gonadotropin hormones, and, in obese men, lower testosterone is accompanied by diminished LH. Taken together, these findings indicate central dysregulation of the hypothalamic–pituitary–gonadal axis, specifically at the level of the GnRH neuron function, which is the final brain output for the regulation of reproduction. Obesity is a state of hyperinsulinemia, hyperlipidemia, hyperleptinemia, and chronic inflammation. Herein, we review recent advances in our understanding of how these metabolic and immune changes affect hypothalamic function and regulation of GnRH neurons. In the latter part, we focus on neuroinflammation as a major consequence of obesity and discuss findings that reveal that GnRH neurons are uniquely positioned to respond to inflammatory changes.
A Novel Anti-Cd40 Monoclonal Antibody, Iscalimab, for Control of Graves’ Hyperthyroidism – A Proof-Of-Concept Trial
Authors: Kahaly G J , Stan M N , Frommer L , Gergely P , Colin L , Amer A , Schuhmann I , Espie P , Rush J S , Basson C , He Y L
Published: September 2019

Context

The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves’ disease (GD) by promoting auto-reactive B cell activation.

Objective

Evaluate efficacy and safety of a human, blocking, non-depleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD

Design

Open label, phase II proof-of-concept study

Setting

Multicenter

Patients

Fifteen with GD

Intervention

Patients received five doses of iscalimab at 10 mg/kg intravenously over 12 weeks.

Main outcome measures

Thyroid-related hormones and autoantibodies, plasma soluble CD40, free CD40 on B cells, soluble CXCL13, pharmacokinetics, and safety were assessed.

Results

The iscalimab intervention resulted in complete CD40 engagement for up to 20 weeks. A clinical response and biochemical euthyroidism was observed in seven of 15 (47%) patients. Free and total T3 and T4 normalized in seven patients who did not receive any rescue medication with anti-thyroid drugs (ATD), and 2/15 (13.3%) showed normal TSH. Six (40%) patients required ATD. Four of seven responders relapsed after treatment completion. Serum concentrations of thyrotropin receptor autoantibodies (TSH-R-Ab) significantly declined in all patients (mean 15.3 IU/L versus 4.0 IU/L, 66% reduction, P<0.001) and TSH-R-Ab levels normalized in four (27%). Thyroperoxidase and thyroglobulin autoantibodies significantly decreased in responders. Iscalimab rapidly reduced serum CXCL13 concentrations (P<0.001). Twelve (80.0%) patients reported at least one adverse event (AE). All treatment-related AE were mild or moderate and resolved by end of the study.

Conclusion

Iscalimab was generally safe and clinically effective in a subgroup of hyperthyroid GD patients. The potential therapeutic benefit of Iscalimab should be further tested.
Opioids and their endocrine effects: A systematic review and meta-analysis
Authors: de Vries Friso , Bruin Mees , Lobatto Daniel J , Dekkers Olaf M , Schoones Jan W , van Furth Wouter R , Pereira Alberto M , Karavitaki Niki , Biermasz Nienke R , Zamanipoor Najafabadi Amir H
Published: September 2019

Context

The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear.

Objective

The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function.

Methods

Eight electronic databases were searched for articles published up to May 8, 2018. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals. This study is reported following the PRISMA- and MOOSE-guidelines.

Data Synthesis

52 studies (22 low risk of bias) were included describing 18,428 subjects, consisting of patients with chronic pain (n=21 studies), or on maintenance treatment for opioid addiction (n=9) and healthy volunteers (n=4). The most frequently used opioid was methadone (n=13 studies), followed by morphine (n=12). Prevalence of hypogonadism was 63% (95% CI: 55-70%, 15 studies, 3,250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and non-dynamic testing was 15% (95% CI: 6-28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16-33%, 2 studies, n=97 patients). In 5 out of 7 studies hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo-pituitary-thyroid axes were described.

Conclusions

Hypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately a fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.
Iron-induced transferrin receptor-1 mRNA destabilization: A response to “Neither miR-7-5p nor miR-141-3p is a major mediator of iron-responsive transferrin receptor-1 mRNA degradation”
Authors: Miyazawa Masaki , Bogdan Alexander R. , Hashimoto Kazunori , Tsuji Yoshiaki
Published: September 2019

We read with great interest the Divergent Views article by Connell and colleagues disputing our recent publication describing a role for two microRNAs in the iron-mediated regulation of transferrin receptor 1 (TfR1) mRNA stability. Our publication sought to shed light on a long-standing question in the field of cellular iron metabolism, and we welcome commentary and critique. However, there are several critical issues contained in the article by Connell and colleagues that require further consideration. We appreciate the opportunity to reply here.
Case Report: Borderline tumor and primary peritoneal carcinoma - a rare synchronism
Authors: Rei Mariana , Raposo Sofia , Figueiredo Paulo , Sousa Rita , Sá Luís
Published: September 2019

Ovarian borderline serous tumors present with peritoneal involvement in 20% of cases, either as non-invasive or invasive implants, also known as extraovarian low-grade serous carcinoma. The coexistence of high-grade serous carcinoma is rare, suggesting a synchronous neoplasia with a distinct and independent tumor biology and behavior. We aim to describe a case of a synchronous ovary-peritoneum neoplasia: serous borderline tumor and primary peritoneal high-grade serous carcinoma. A discussion and literature review concerning the optimal diagnostic and therapeutic approach is provided.
Facebook Powered Measurement and Evaluation for Iron Folic Acid Health Intervention in India
Authors: Bernard Drew , McCullough Chris , Francis Sarah , Holton Avery , Diamond-Smith Nadia
Published: September 2019

As the media landscape changes and billions of people around the world turn to Facebook, Instagram, WhatsApp, and other social media platforms for information and social interactions, the need to develop effective methods of leveraging social media for social behavior change communication (SBCC) becomes increasingly important. Yet, in order for the public health sector to embrace social media for SBCC, we must have methods for measuring the impact of social media-based SBCC.

In this letter, we share a new approach for measurement and evaluation of social media-based SBCC campaigns. The approach was developed as part of an iron-folic acid health intervention targeting young women in two states in northern India; Uttar Pradesh and Maydar Pradesh.
Innovative Collaboration Between Industry and Academics: Meeting Industry’s Future Talent Requirements
Authors: Bowers Melissa R. , Gilbert Kenneth C. , Noon Charles E.
Published: September 2019

The authors share their experience in creating and maintaining the Master of Science in Business Analytics program at the Haslam College of Business at the University of Tennessee. The Haslam College of Business received the 2018 UPS George D. Smith Prize for the program, acknowledging a collaboration with industry in preparing students to be effective practitioners of operations research/management science.
Characteristics of people with pressure ulcers using one year's routinely collected data in a defined diverse community
Authors: Jackson Debra , Hutchinson Marie , Neville Stephen , Padula William V. , Usher Kim , Gardner Sarah , Betteridge Ria , Durrant Lisa
Published: September 2019

Objective:

To determine if meaningful patient characteristics pertaining to pressure ulcers (PU) can be derived from routinely collected community health data.

Methods:

A retrospective cohort analysis of records was carried out. To provide a detailed dataset on PU for the community of interest, demographic, general medical and PU data were extracted from mandatory incident reports and audit of electronic and paper medical records. This study is reported in accordance with the RECORD Guidelines from the Equator Network. Adult patients were enrolled from a district nursing service in the target region (n=1085) during 2015. The target region was based on a geographical region bounded by a single postcode district (target region) consisting of 62,000 people of whom approximately 50,000 were adults, 3000 of whom were aged >75 years.

Results:

The total number of recorded PUs was n=137 in 103 individuals. Data from mandatory incident reports was obtainable for nearly all variables. Electronic and paper medical records were less reliable due to missing data.

Conclusion:

Detailed characteristics of community-dwelling PU patients can be derived from routinely collected data, and provides various forms and levels of information which could feed into different projects. The use of mandatory reporting fields increases the level of reporting and reduces missing data. Data enriched with information from electronic and paper records could inform the addition of variables to mandatory forms to improve characterisation of community dwellers with PUs.
Predictive factors for category II pressure ulcers in older patients with hip fractures: a prospective study
Authors: Gazineo Domenica , Chiari Paolo , Chiarabelli Matteo , Morri Mattia , D'Alessandro Fabio , Sabattini Tania , Ambrosi Elisa , Forni Cristiana
Published: September 2019

Objective:

To identify the incidence of category II or higher hospital-acquired pressure ulcers (HAPU) and significantly associated factors in older patients with hip fractures. PUs are a frequent complication in hip fracture patients, negatively impacting patients' quality of life, the health-care system and society.

Method:

A prospective cohort study was conducted. A consecutive sample of patients with pertrochanteric, femoral neck or subtrochanteric fractures requiring surgical treatment, were included. A stepwise, multiple regression was performed to identify factors associated with PU development.

Results:

A total of 761 patients aged ≥65 years were sampled. The incidence of category II or higher PUs was 12%. The study identified five factors that were significantly, independently associated with category II or higher PU development, including a higher preoperative Braden score (Hazard Ratio [HR]: 0.884; 95% confidence interval [CI]: 0.806–0.969), surgical procedure with osteosynthesis (HR 1.876; 95%CI: 1.183–2.975), a higher percentage of days with the presence of foam valve before surgery (HR: 1.010; 95%CI: 1.010–1.023) and a urinary catheter (HR: 1.013; 95%CI: 1.006–1.019) and diaper (HR: 1.007; 95% CI 1.001–1.013) in the postoperative period.

Conclusion:

Attention should be given by clinical staff to avoiding the use of foam valves, to limiting the use of diapers and to early removal of urinary catheters.
Biofilm management using monofilament fibre debridement technology: outcomes and clinician and patient satisfaction
Authors: Roes Claas , Calladine Leanne , Morris Clare
Published: September 2019

Objective:

Best practice in wound bed preparation and biofilm-based wound management includes debridement to create a clean wound bed and to assist in minimising the redevelopment of biofilm. Biofilm that is not removed inhibits healing and redevelops if not prevented from doing so with topical antimicrobial agents. Monofilament fibre debriding technology (MFDT) is used for effective and rapid mechanical debridement of loose material, slough and biofilm. The objective of this evaluation was to determine the clinical effect and consequential levels of health professional and patient satisfaction with the results of a biofilm pathway that included MFDT to achieve debridement.

Methods:

This non-comparative, open label evaluation was conducted in static and non-static wounds that required debridement. MFDT was used to debride in a two-week evaluation of a biofilm pathway. Wounds were debrided three times in week one and twice in week two. Each debridement was followed by treatment with an antimicrobial dressing. Other care included secondary dressings and compression delivered according to local practice, guidelines and formularies. After the clinical evaluation, health professionals were invited to complete an online survey of the clinical outcomes and their satisfaction with the biofilm pathway.

Results:

There were 706 health professionals who provided answers to the survey questions. Wound types evaluated were leg ulcers (67.4%), pressure ulcers (10%), dehisced surgical wounds (1.7%), diabetic foot ulcers (7.4%) and other wounds (13.4%). Of the wounds, 9% were reported as non-static despite the eligibility criteria. Not all wounds followed the pathway. The most frequently-used antimicrobial was silver. Non-antimicrobial products used included all-in-one dressings, other secondary dressings and compression. There was a change in 77% of wounds overall after two weeks. Change was reported almost equally for both static and non-static wounds. Health professionals who did or did not follow the pathway were ‘completely satisfied’ or ‘satisfied’ with the overall clinical outcome 96% and 95%, respectively. Of the patients, 77% were ‘completely satisfied’ or ‘satisfied’ with healing after following the pathway, as reported by the treating health professional.

Conclusion:

The biofilm pathway that includes MFDT appears effective. Wounds managed on the pathway were debrided effectively and healing progressed to the satisfaction of both health professionals and patients.