bluuebunny/crossref_metadata_2025 huggingface dataset:
Favorable outcomes of hematopoietic stem cell transplantation in children and adolescents with Diamond-Blackfan anemia
Authors: Strahm Brigitte , Loewecke Felicia , Niemeyer Charlotte M. , Albert Michael , Ansari Marc , Bader Peter , Bertrand Yves , Burkhardt Birgit , Da Costa Lydie M. , Ferster Alina , Fischer Alexandra , Güngör Tayfun , Gruhn Bernd , Hainmann Ina , Kapp Friedrich , Lang Peter , Müller Ingo , Schulz Ansgar , Szvetnik Amina , Wlodarski Marcin , Noellke Peter , Leblanc Thierry , Dalle Jean-Hugues
Published: April 2020

Diamond-Blackfan anemia (DBA) is a congenital pure red cell aplasia associated with congenital abnormalities and cancer predisposition. Allogeneic hematopoietic stem cell transplantation (HSCT) can correct the hematological phenotype and is indicated in transfusion-dependent patients. In 70 children reported to the German DBA and French HSCT registries, HSCT was performed from 1985 to 2017. Median age at HSCT was 5.5 years (range, 0.9-17.3 years). Two-thirds of patients (64%) were transplanted from a matched sibling donor (MSD), and most procedures were performed after the year 1999 (73%). Primary engraftment was achieved in all patients. One patient developed secondary graft failure. Cumulative incidence of acute graft-versus-host disease (GVHD) was 24% for °II-IV (95% confidence interval [CI], 16% to 37%) and 7% for °III-IV (95% CI, 3% to 17%); cumulative incidence of chronic GVHD was 11% (95% CI, 5% to 22%). The probability of chronic GVHD-free survival (cGFS) was 87% (95% CI, 79% to 95%) and significantly improved over time (<2000: 68% [95% CI, 47% to 89%] vs ≥2000: 94% [95% CI, 87% to 100%], P < .01). cGFS was comparable following HSCT from a MSD and an unrelated donor (UD). Of note, no severe chronic GVHD or deaths were reported following MSD-HSCT after 1999. The difference of cGFS in children transplanted <10 years of age compared with older patients did not reach statistical significance (<10 years: 90% [95% CI, 81% to 99%] vs 10-18 years 78% [95% CI, 58% to 98%]). In summary, these data indicate that HSCT is efficient and safe in young DBA patients and should be considered if a MSD or matched UD is available. HSCT for transfusion dependency only must be critically discussed in older patients.
Baseline FDG-PET/CT detects bone marrow involvement in follicular lymphoma and provides relevant prognostic information
Authors: Nakajima Reiko , Moskowitz Alison J. , Michaud Laure , Mauguen Audrey , Batlevi Connie Lee , Dogan Ahmet , Schöder Heiko
Published: April 2020

In follicular lymphoma (FL), detection of bone marrow (BM) involvement (BMI) by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) improves the accuracy of staging vs BM biopsy (BMB) alone. Our objective was to determine the diagnostic utility of PET for BMI FL and the prognostic value of BMI by PET (positive PET result [PET+]). Records of patients (2002-2016) with PET and BMB at the time of initial treatment were reviewed. BMI was identified by positive BMB result (BMB+) and/or unifocal or multifocal BM FDG uptake on blindly reviewed PET scans with no corresponding CT abnormality (PET+). Among 261 patients, BMI was diagnosed in 78 patients (29.9%) by PET+, in 81 patients (31.0%) by BMB+, and in 113 patients (43.3%) by either PET+ or BMB+. PET+ upstaged 24 patients to stage IV, including 10 from stages I or II to stage IV. Median duration of follow-up was 6.0 years (range, 0-16.6 years). In univariate analysis, a high Follicular Lymphoma International Prognosis Index (FLIPI) score, PET+, and BMB+ correlated with shorter progression-free survival (PFS; all P ≤ .03), and high FLIPI, PET+, and combined PET+ and BMB+ with shorter overall survival (OS; all P ≤ .01). In multivariate analysis, PET+ was the only independent predictor of PFS, whereas high FLIPI score and PET+ predicted OS (P ≤ .03). Combined PET and BMB identify BMI more accurately than either BMB or PET alone, but BMB rarely adds critical information. For patients initiating treatment of FL, identification of BMI by PET is predictive of PFS and OS.
Hydrothermal Synthesis of Silver Decorated Reduced Graphene Oxide (rGO) Nanoflakes with Effective Photocatalytic Activity for Wastewater Treatment
Authors: Ikram Muhammad , Raza Ali , Imran Muhammad , Ul-Hamid Anwar , Shahbaz Atif , Ali Salamat
Published: April 2020

Graphene oxide (GO) was obtained through modified hummers method, and reduced graphene oxide (rGO) was acquired by employing heat treatment. Various concentrations (2.5, 5, 7.5, and 10 wt. %) of silver (Ag) were incorporated in GO nanosheets by adopting hydrothermal approach. Synthesized Ag decorated rGO photocatalyst Ag/rGO was characterized using X-ray diffraction (XRD) to determine phase purity and crystal structure. XRD patterns showed the formation of GO to Ag/rGO. Molecular vibration and functional groups were determined through Fourier Transform Infrared spectroscopy (FTIR). Optical properties and a decrease in bandgap with insertion of Ag were confirmed with UV-Visible (Uv-Vis) spectrophotometer and photoluminescence (PL). Electronic properties and disorders in carbon structures were investigated through Raman spectroscopy that revealed the existence of characteristic bands (D and G). Surface morphology of prepared samples was examined with field emission scanning electron microscope (FESEM). Homogeneous distribution, size, and spherical shape of Ag NPs over rGO sheets were further confirmed with the help of high-resolution transmission electron microscope (HR-TEM). Dye degradation of doped and undoped samples was examined through Uv-Vis spectra. Experimental results indicated that photocatalytic activity of Ag@rGO enhanced with increased doping ratio owing to diminished electron-hole pair recombination. Therefore, it is suggested that Ag@rGO can be used as a beneficial and superior photocatalyst to clean environment and wastewater.
Evolution of emergency medical services in the Kingdom of Bahrain
Authors: Abuzeyad Feras H. , Al Qasim Ghada , Alqasem Leena , Al Farras Mudhaffar I.
Published: April 2020

Emergency medical services (EMS) is crucial to any healthcare system, especially in urban countries. The Kingdom of Bahrain has always strived to develop healthcare services throughout the Kingdom including EMS. Like any other country, the Kingdom has gone through several stages in the provision of EMS. This article will focus on the development of EMS in the Kingdom and its evolution from a scattered hospital-based system to a unified system, which ensures ease of access for the population and speed of delivery to the healthcare facilities. The major focus will be the most recent national project which is the National Ambulance.
Basic biochemical characterization of cytosolic enzymes in thymidine nucleotide synthesis in adult rat tissues: implications for tissue specific mitochondrial DNA depletion and deoxynucleoside-based therapy for TK2-deficiency
Authors: Wang Liya , Sun Ren , Eriksson Staffan
Published: April 2020

Background

Deficiency in thymidine kinase 2 (TK2) or p53 inducible ribonucleotide reductase small subunit (p53R2) is associated with tissue specific mitochondrial DNA (mtDNA) depletion. To understand the mechanisms of the tissue specific mtDNA depletion we systematically studied key enzymes in dTMP synthesis in mitochondrial and cytosolic extracts prepared from adult rat tissues.

Results

In addition to mitochondrial TK2 a cytosolic isoform of TK2 was characterized, which showed similar substrate specificity to the mitochondrial TK2. Total TK activity was highest in spleen and lowest in skeletal muscle. Thymidylate synthase (TS) was detected in cytosols and its activity was high in spleen but low in other tissues. TS protein levels were high in heart, brain and skeletal muscle, which deviated from TS activity levels. The p53R2 proteins were at similar levels in all tissues except liver where it was ~ 6-fold lower. Our results strongly indicate that mitochondria in most tissues are capable of producing enough dTTP for mtDNA replication via mitochondrial TK2, but skeletal muscle mitochondria do not and are most likely dependent on both the salvage and de novo synthesis pathways.

Conclusion

These results provide important information concerning mechanisms for the tissue dependent variation of dTTP synthesis and explained why deficiency in TK2 or p53R2 leads to skeletal muscle dysfunctions. Furthermore, the presence of a putative cytosolic TK2-like enzyme may provide basic knowledge for the understanding of deoxynucleoside-based therapy for mitochondrial disorders.
Community intervention for cardiovascular disease risk factors in Kalutara, Sri Lanka
Authors: Gamlath L. , Nandasena S. , Silva P. de , Morrell S. , Linhart C. , Lin S. , Sharpe A. , Nathan S. , Taylor R.
Published: April 2020

Background

The effectiveness of a 2015–17 community intervention to reduce cardiovascular disease (CVD) and type 2 diabetes (T2DM) risk factors is assessed in a Sri Lanka adult population, using a before-and-after study design.

Methods

Four contiguous Public Health Midwife (PHM) areas in Kalutara district (Western Province) were exposed to a Sri Lankan designed community health promotion initiatives (without screening) to lower CVD and T2DM risk factors. Pre- and post-intervention surveys (2014, n=1,019; 2017, n=908) were of 25–64 year males (M) and females (F) from dissimilar randomly selected clusters (villages or settlements) from PHMs, with probability of selection proportional to population size, followed by household sampling, then individual selection to yield equal-probability samples. Differences in resting blood pressure (BP), fasting plasma glucose (FPG), total cholesterol, body mass index and tobacco smoking, adjusting for cluster sampling, age and socio-economic differences, were examined.

Results

Hypertension prevalence declined from 25% to 16% (F) (p<.0001), and 21% to 17% (M). Both mean systolic and diastolic BP declined. T2DM declined from 18% to 13% (F), and 18% to 15% (M), as did mean fasting plasma glucose. Elevated total cholesterol declined from 21% to 15% in women (p=0.003) and mean cholesterol declined. Frequency distributions, medians and means of these continuous CVD risk factors shifted to lower levels, and were mostly statistically significant (p< 0.05).

Conclusions

Community health promotion can lower key CVD and T2DM risk factors. Lowering tobacco consumption in males and obesity remain challenges in Sri Lanka.
EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors
Authors: Chiang Anne C. , Fernandes Ancilla W. , Pavilack Melissa , Wu Jennifer W. , Laliberté François , Duh Mei Sheng , Chehab Nabil , Subramanian Janakiraman
Published: April 2020

Background

The objective of this study was to investigate real-world EGFR mutation testing in patients with metastatic non-small cell lung cancer (NSCLC) upon progression on first−/second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), and subsequent treatments received.

Methods

Flatiron Health electronic health records-derived database was used to identify adult patients with metastatic NSCLC treated with first−/second-generation EGFR-TKI from 11/2015–09/2017, with start of first EGFR-TKI defined as the index date. Patients were stratified by receipt of EGFR-TKI as first-line (1 L) or later-line (2 L+) treatment. Mutation testing and subsequent therapies following first−/second-generation EGFR-TKI were described.

Results

Overall, 782 patients (1 L = 435; 2 L+ =347) were included. Median age was 69.0 years, 63.6% were female, 56.3% were white, 87.1% were treated in community-based practices, and 30.1% of patients died during the study period; median follow-up was 309.0 days. Among the 294 (1 L = 160; 2L+ =134) patients who received subsequent therapies, treatments included chemotherapy only (1 L = 15.6%; 2L+ =21.6%), immunotherapy only (1 L = 13.8%; 2 L+ =41.0%), and targeted therapies (1 L = 70.0%; 2 L+ =36.6%). Specifically, 40 (25.0%) 1 L patients and 7 (5.2%) 2 L+ patients received osimertinib as subsequent therapy. Before the start of subsequent therapy, EGFR T790M resistance mutation testing was performed in 88 (29.9%) patients (1 L = 63 [39.4%]; 2 L+ =25 [18.7%]). Of these patients, 25 (28.4%) were T790M positive, among whom 24 (96.0%) received osimertinib.

Conclusions

A third of patients received subsequent therapies on disease progression; only 30% of these were tested for EGFR-TKI resistance mutation, prior to receiving subsequent therapies. These results highlight the importance of choosing treatments in the 1 L setting that optimize benefits for patients with EGFR-mutated NSCLC.
Cumulative psychosocial factors are associated with cardiovascular disease risk factors and management among African Americans in the Jackson Heart Study
Authors: Sims Mario , Glover Lá Shauntá M. , Gebreab Samson Y. , Spruill Tanya M.
Published: April 2020

Background

Racial disparities in cardiovascular disease (CVD) have been attributed in part to negative psychosocial factors. Prior studies have demonstrated associations between individual psychosocial factors and CVD risk factors, but little is known about their cumulative effects.

Methods

Using the Jackson Heart Study, we examined the cross-sectional associations of cumulative psychosocial factors with CVD risk factors among 5306 African Americans. We utilized multivariable Poisson regression to estimate sex-stratified prevalence ratios (PR 95% confidence interval-CI) of obesity, hypertension and diabetes prevalence and hypertension and diabetes control with negative affect (cynicism, anger-in, anger-out, depressive symptoms and cumulative negative affect) and stress (global stress, weekly stress, major life events-MLEs and cumulative stress), adjusting for demographics, socioeconomic status, and behaviors.

Results

After full adjustment, high (vs. low) cumulative negative affect was associated with prevalent obesity among men (PR 1.36 95% CI 1.16–1.60), while high (vs. low) cumulative stress was similarly associated with obesity among men and women (PR 1.24 95% CI 1.01–1.52 and PR 1.13 95% CI 1.03–1.23, respectively). Psychosocial factors were more strongly associated with prevalent hypertension and diabetes among men than women. For example, men who reported high cynicism had a 12% increased prevalence of hypertension (PR 1.12, 95% CI 1.03–1.23). Psychosocial factors were more strongly associated with lower hypertension and diabetes control for women than men. Women who reported high (vs. low) cynicism had a 38% lower prevalence of hypertension control (PR 0.62, 95% CI 0.46–0.84).

Conclusions

Cumulative psychosocial factors were associated with CVD risk factors and disease management among African Americans. The joint accumulation of psychosocial factors was more associated with risk factors for men than women.
A prospective study on the effect of self-reported health and leisure time physical activity on mortality among an ageing population: results from the Tromsø study
Authors: Opdal Ida Marie , Larsen Lill Sverresdatter , Hopstock Laila Arnesdatter , Schirmer Henrik , Lorem Geir Fagerjord
Published: April 2020

Background

The prevailing Western ideal of ageing in place, with the option to stay at home as one ages, has led to the development of physical activity guidelines for people of advanced age to increase their quality of life and promote their functional abilities. This study investigates the effect of self-reported health and physical activity on mortality and examines how levels of age-specific physical activity affect self-reported health trajectories in an ageing cohort.

Methods

The sample cohort of the population-based Tromsø Study consists of 24,309 participants aged 25–97 years at baseline. This study involved a survival analysis from 1994 to 2015 and included those who completed two or more surveys (n = 12,241) between 1994 and 2008. The purpose was to examine the relationship between physical activity and self-reported health throughout life using a random coefficient model analysis.

Results

Being sedentary was associated with an increased risk of mortality in the ageing cohort. Subjects who reported neither light physical activity nor hard physical activity had a 57% (OR 1.57, 1.07–2.31) increased risk of all-cause death. Both hard (OR 2.77, 2.35–3.26) and light (OR 1.52, 1.32–1.76) physical activity were positively associated with self-reported health. The effect was age dependent. Vigorous physical activity was most beneficial for individuals younger than 40 years old, while moderate physical activity levels prolonged the period in which good self-reported health was likely.

Conclusions

Poor self-reported health and being sedentary were independently associated with an increased risk of mortality in the participants. Furthermore, physical activity prolonged the period of good self-reported health among older adults in two ways: physical activity habits from early adulthood and onwards were beneficial to self-reported health at an advanced age, and self-reported health was dependent on engagement in moderate intensity physical activity after approximately 65 years of age.
Organ/space infection is a common cause of high output stoma and outlet obstruction in diverting ileostomy
Authors: Hara Yutaro , Miura Takuya , Sakamoto Yoshiyuki , Morohashi Hajime , Nagase Hayato , Hakamada Kenichi
Published: April 2020

Background

The objectives of this study are to identify causes of high-output stoma (HOS) and outlet obstruction (OO), which are major complications of diverting ileostomy.

Methods

A retrospective analysis was performed in 103 patients who underwent colorectal surgery and diverting ileostomy between December 2015 and November 2018.

Results

HOS was found in 32 patients (31.1%) and OO in 19 (18.4%). Organ/space surgical site infection (SSI), anastomotic leakage and OO were significant HOS-related factors in univariate analysis, and OO (odds ratio [OR] 3.39, p = 0.034) was a independent HOS-related factor in multivariate analysis. Organ/space SSI and male were significant OO-related factors in univariate analysis, and organ/space SSI (OR 3.77, p = 0.018) was a independent OO-related factor in multivariate analysis. The white blood cell (WBC) count on postoperative day (POD) 3 was significantly higher in the HOS group compared to the non-HOS group (9765 vs. 8130 /mL, p < 0.05), and the WBC count (9400 vs. 7475 /mL, p < 0.05) and C-reactive protein level (6.01 vs. 2.92 mg/L, p < 0.05) on POD 6 were significantly higher in the OO group compared to the non-OO group.

Conclusion

Organ/space infection is involved in the common pathology of HOS and OO. Decreased intestinal absorption due to intestinal edema caused by organ/space SSI and relative stenosis at the abdominal wall-penetrating site are major causes of HOS and OO.
Phytoremediation effect of Medicago sativa colonized by Piriformospora indica in the phenanthrene and cadmium co-contaminated soil
Authors: Li Liang , Zhu Pengyue , Wang Xiaoyang , Zhang Zhenhua
Published: April 2020

Background

The coexistence of polycyclic aromatic hydrocarbons (PAHs) and heavy metals has deleterious effects on environmental quality. Few reports have studied the mechanisms of plant inoculation with Piriformospora indica to remediate PAH-metal co-contaminated soil by analyzing the chemical speciation of the contaminants. This study investigated the influence of the inoculation of Medicago sativa with P. indica to remediate soil co-contaminated with phenanthrene (a kind of PAH) and cadmium (a heavy metal) by analyzing plant growth, physiological parameters and chemical speciation in rhizosphere and nonrhizosphere soils.

Results

The presence of P. indica significantly increased plant tolerance, chlorophyll a, chlorophyll b, maximum quantum efficiency of PSII photochemistry and electron transport rate values in phenanthrene- and/or cadmium-contaminated soil. P. indica inoculation in M. sativa roots increased fluorescein diacetate activities in soils contaminated with phenanthrene, cadmium or both, especially in the nonrhizosphere. The presence of phenanthrene prevented the inoculated plant from accumulating cadmium to some extent, whereas the presence of cadmium did not prevent the degradation of phenanthrene in either the rhizosphere or the nonrhizosphere after P. indica colonization. Although the low bioavailability of cadmium in the rhizosphere restricted its transportation into the stem, P. indica colonization in plants effectively increased cadmium accumulation in roots in soil co-contaminated with cadmium and phenanthrene.

Conclusions

In conclusion, this work provides a theoretical basis for the use of P. indica combined with M. sativa for the remediation of PAH-metal co-contaminated soil.
The significance of resilience in mental health promotion of marriage immigrant women: a qualitative study of factors and processes
Authors: Jo Yeonjae
Published: April 2020

Background

This study explores a series of processes in which marriage immigrant women achieve positive mental health status after experiencing various marriage- and migrant-related difficulties through the framework of resilience theory. As marriage immigrant women face greater barriers to public health services than non-immigrant women, it is necessary to understand the related factors, process, and context to address these barriers and strengthen available assets.

Methods

A qualitative case study design was used with the phenomenological approach. Eleven mental health promotion program managers and 12 marriage immigrant women from who experienced resilience were recruited from four public-funded multicultural community centers in Seoul and Gyeonggi-do, South Korea, between December 2015 and March 2016. Using data from in-depth semi-structured face-to-face interviews, the author applied theme analysis informed by the resilience theory in order to identify factors that affect resilience and its development process.

Results

Findings indicated that the process of resilience follows enduring difficulties, collapse of stability, access to professional help, professional and social support, and experience of growth. A combination of the staged process of growth, absence of partner support, children as a driving force for change, the need for economic activity, factors affecting difference in growth: satisfaction levels of women’s need for recognition, respect, and reward, and level of spousal support were identified as factors affecting marriage immigrant women’s resilience.

Conclusions

Spouses, children, and economic activity play key roles in resilience in positive and negative ways. The existing information barrier should be addressed at a structural level to improve the mental health of marriage immigrant women, and the optimum time for intervention is suggested within 2 years post-migration. Efforts to build supportive relationships with Korean spouses and meet the women’s needs for recognition, respect, and reward may also help promote these women’s resilience.
Uncovering the mechanism of the effects of Paeoniae Radix Alba on iron-deficiency anaemia through a network pharmacology-based strategy
Authors: Ye Xian-wen , Deng Ya-ling , Xia Lan-ting , Ren Hong-min , Zhang Jin-lian
Published: April 2020

Background

Paeoniae Radix Alba, the root of the plant Paeonia lactiflora Pall, is a common blood-enriching drug in traditional Chinese medicine. Its effectiveness in the clinical treatment of anaemia is remarkable, but its potential pharmacologic mechanism has not been clarified.

Methods

In this study, the potential pharmacologic mechanism of Paeoniae Radix Alba in the treatment of iron-deficiency anaemia was preliminarily elucidated through systematic and comprehensive network pharmacology.

Results

Specifically, we obtained 15 candidate active ingredients from among 146 chemical components in Paeoniae Radix Alba. The ingredients were predicted to target 77 genes associated with iron-deficiency anaemia. In-depth analyses of these targets revealed that they were mostly associated with energy metabolism, cell proliferation, and stress responses, suggesting that Paeoniae Radix Alba helps alleviate iron-deficiency anaemia by affecting these processes. In addition, we conducted a core target analysis and a cluster analysis of protein-protein interaction (PPI) networks. The results showed that four pathways, the p53 signalling pathway, the IL-17 signalling pathway, the TNF signalling pathway and the AGE-RAGE signalling pathway in diabetic complications, may be major pathways associated with the ameliorative effects of Paeoniae Radix Alba on iron-deficiency anaemia. Moreover, molecular docking verified the credibility of the network for molecular target prediction.

Conclusions

Overall, this study predicted the functional ingredients in Paeoniae Radix Alba and their targets and uncovered the mechanism of action of this drug, providing new insights for advanced research on Paeoniae Radix Alba and other traditional Chinese medicines.
Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice
Authors: Bao Xiaoyan , Qian Kang , Yao Ping
Published: April 2020

Background

Exenatide is an insulinotropic peptide drug for type 2 diabetes treatment with low risk of hypoglycemia, and is administrated by subcutaneous injection. Oral administration is the most preferred route for lifelong treatment of diabetes, but oral delivery of peptide drug remains a significant challenge due to the absorption obstacles in gastrointestinal tract. We aimed to produce exenatide-loaded nanoparticles containing absorption enhancer, protectant and stabilizer using FDA approved inactive ingredients and easy to scale-up method, and to evaluate their long-term oral therapeutic effect in type 2 diabetes db/db mice.

Results

Two types of nanoparticles, named COM NPs and DIS NPs, were fabricated using anti-solvent precipitation method. In COM NPs, the exenatide was complexed with cholic acid and phosphatidylcholine to increase the exenatide loading efficiency. In both nanoparticles, zein acted as the cement and the other ingredients were embedded in zein nanoparticles by hydrophobic interaction. Casein acted as the stabilizer. The nanoparticles had excellent lyophilization, storage and re-dispersion stability. Hypromellose phthalate protected the loaded exenatide from degradation in simulated gastric fluid. Cholic acid promoted the intestinal absorption of the loaded exenatide via bile acid transporters. The exenatide loading efficiencies of COM NPs and DIS NPs were 79.7% and 53.6%, respectively. The exenatide oral pharmacological availability of COM NPs was 18.6% and DIS NPs was 13.1%. COM NPs controlled the blood glucose level of the db/db mice well and the HbA1c concentration significantly decreased to 6.8% during and after 7 weeks of once daily oral administration consecutively. Both DIS NPs and COM NPs oral groups substantially increased the insulin secretion by more than 60% and promoted the β-cell proliferation by more than 120% after the 7-week administration.

Conclusions

Both COM NPs and DIS NPs are promising systems for oral delivery of exenatide, and COM NPs are better in blood glucose level control than DIS NPs. Using prolamin to produce multifunctional nanoparticles for oral delivery of peptide drug by hydrophobic interaction is a simple and effective strategy.
Primary lymph node gastrinoma: a case report and review of the literature
Authors: Cavalcanti Elisabetta , Stasi Elisa , Coletta Sergio , Lorusso Dionigi , Rinaldi Caterina Mammone , Armentano Raffaele
Published: April 2020

Background

Gastrinoma is a rare form of neuroendocrine neoplasm. The presence of a primary lymph node localization of gastrinoma is a much debated and controversial topic in the literature, as regards whether these cases represent metastatic disease from an as yet unidentified primary tumor, or the de novo occurrence of a gastrinoma in a lymph node.

Case presentation

We report the case of a 24-year-old male with intense epigastric pain treated at the beginning with high dose proton pump inhibitors. Further workup with CT and subsequent laparotomy revealed a single peripancreatic lymph node. Histological examination highlighted a well-differentiated neuroendocrine tumor.

Conclusion

This case underlines that the primitive lymph node gastrinoma is a distinct nosological entity with a precise location in the context of rare neuroendocrine tumors that should be considered when specific symptoms are associated with the identification of isolated lymph nodes, after excluding any possible primitive locations of neoplastic localization.
Cross-sectional and longitudinal associations between physical activity, sedentary behaviour and bone stiffness index across weight status in European children and adolescents
Authors:   On behalf of the IDEFICS and I. Family Consortia, Cheng Lan , Pohlabeln Hermann , Ahrens Wolfgang , Lauria Fabio , Veidebaum Toomas , Chadjigeorgiou Charalambos , Molnár Dénes , Eiben Gabriele , Michels Nathalie , Moreno Luis A. , Page Angie S. , Pitsiladis Yannis , Hebestreit Antje
Published: April 2020

Background

The associations between physical activity (PA), sedentary behaviour (SB) and bone health may be differentially affected by weight status during growth. This study aims to assess the cross-sectional and longitudinal associations between PA, SB and bone stiffness index (SI) in European children and adolescents, taking the weight status into consideration.

Methods

Calcaneus SI was first measured by quantitative ultrasound among children aged 2–9 years old in 2007/08. It was measured again after 2 years in the IDEFICS study and after 6 years in the I. Family study. A sample of 2008 participants with time spent at sports clubs, watching TV and playing computer/games self-reported by questionnaire, and a subsample of 1037 participants with SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) objectively measured using Actigraph accelerometers were included in the analyses. Weight status was defined as thin/normal and overweight/obese according to the extended International Obesity Task Force criteria. Linear mixed-effects models were used to estimate the cross-sectional and longitudinal associations between PA, SB and SI percentiles, stratified by weight status.

Results

The cross-sectional association between weekly duration of watching TV and SI percentiles was negative in thin/normal weight group (β = − 0.35, p = 0.008). However, baseline weekly duration of watching TV (β = − 0.63, p = 0.021) and change after 2 years (β = − 0.63, p = 0.022) as well as the change in weekly duration of playing computer/games after 6 years (β = − 0.75, p = 0.019) were inversely associated with corresponding changes in SI percentiles in overweight/obese group. Change in time spent at sports clubs was positively associated with change in SI percentiles after 2 years (β = 1.28, p = 0.001), with comparable effect sizes across weight status. In the subsample with accelerometer data, we found a positive cross-sectional association between MVPA and SI percentiles in thin/normal weight group. Baseline MVPA predicted changes in SI percentiles after 2 and 6 years in all groups.

Conclusions

Our results suggested the beneficial effect of PA on SI. However, the increasing durations of screen-based SB might be risk factors for SI development, especially in overweight/obese children and adolescents.
Potential of activated microglia as a source of dysregulated extracellular microRNAs contributing to neurodegeneration in amyotrophic lateral sclerosis
Authors: Christoforidou Eleni , Joilin Greig , Hafezparast Majid
Published: April 2020

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron degeneration in adults, and several mechanisms underlying the disease pathology have been proposed. It has been shown that glia communicate with other cells by releasing extracellular vesicles containing proteins and nucleic acids, including microRNAs (miRNAs), which play a role in the post-transcriptional regulation of gene expression. Dysregulation of miRNAs is commonly observed in ALS patients, together with inflammation and an altered microglial phenotype. However, the role of miRNA-containing vesicles in microglia-to-neuron communication in the context of ALS has not been explored in depth. This review summarises the evidence for the presence of inflammation, pro-inflammatory microglia and dysregulated miRNAs in ALS, then explores how microglia may potentially be responsible for this miRNA dysregulation. The possibility of pro-inflammatory ALS microglia releasing miRNAs which may then enter neuronal cells to contribute to degeneration is also explored. Based on the literature reviewed here, microglia are a likely source of dysregulated miRNAs and potential mediators of neurodegenerative processes. Therefore, dysregulated miRNAs may be promising candidates for the development of therapeutic strategies.
Online compensation detecting for real-time reduction of compensatory motions during reaching: a pilot study with stroke survivors
Authors: Cai Siqi , Wei Xuyang , Su Enze , Wu Weifeng , Zheng Haiqing , Xie Longhan
Published: April 2020

Background

Compensations are commonly observed in patients with stroke when they engage in reaching without supervision; these behaviors may be detrimental to long-term functional improvement. Automatic detection and reduction of compensation cab help patients perform tasks correctly and promote better upper extremity recovery.

Objective

Our first objective is to verify the feasibility of detecting compensation online using machine learning methods and pressure distribution data. Second objective was to investigate whether compensations of stroke survivors can be reduced by audiovisual or force feedback. The third objective was to compare the effectiveness of audiovisual and force feedback in reducing compensation.

Methods

Eight patients with stroke performed reaching tasks while pressure distribution data were recorded. Both the offline and online recognition accuracy were investigated to assess the feasibility of applying a support vector machine (SVM) based compensation detection system. During reduction of compensation, audiovisual feedback was delivered using virtual reality technology, and force feedback was delivered through a rehabilitation robot.

Results

Good classification performance was obtained in online compensation recognition, with an average F1-score of over 0.95. Based on accurate online detection, real-time feedback significantly decreased compensations of patients with stroke in comparison with no-feedback condition (p < 0.001). Meanwhile, the difference between audiovisual and force feedback was also significant (p < 0.001) and force feedback was more effective in reducing compensation in patients with stroke.

Conclusions

Accurate online recognition validated the feasibility of monitoring compensations using machine learning algorithms and pressure distribution data. Reliable online detection also paved the way for reducing compensations by providing feedback to patients with stroke. Our findings suggested that real-time feedback could be an effective approach to reducing compensatory patterns and force feedback demonstrated a more enviable potential compared with audiovisual feedback.
The efficacy of positioning stents in preventing Oral complications after head and neck radiotherapy: a systematic literature review
Authors: Chen Dong , Chen Xiaoju , Chen Xinmei , Jiang Nanchuan , Jiang Li
Published: April 2020

Background

Positioning stent in head and neck radiotherapy seems to have benefit to prevent oral complications but it hasn’t been summarized by an evidence-based method.

Objectives

This review aims to evaluate the efficacy of positioning stents in preventing oral complications after radiotherapy.

Methods

We conducted an electronic search in MEDLINE, EMBASE, Cochrane CDSR, and Cochrane CENTRAL database for randomized-controlled clinical trials, controlled clinical trials and cohort studies that assessed oral complications after head and neck radiotherapy with positioning stents. Two reviewers extracted information on radiotherapy, follow-up period, oral complications and assessments independently.

Results

Three RCTs and two cohort studies were included in this review. Oral complications such as mucositis, xerostomia, taste alteration, trismus, salivary changes, dysphagia and pain on swallowing were assessed by different methods in these studies.

Conclusions

Oral complications were common in patients after head and neck radiotherapy. There is insufficient evidence that positioning stents have a preventive effect against xerostomia, and it needs more high-quality and prospective trials with long-term follow-up to support it.
A scoping review and proposed workflow for multi-omic rare disease research
Authors: Kerr Katie , McAneney Helen , Smyth Laura J. , Bailie Caitlin , McKee Shane , McKnight Amy Jayne
Published: April 2020

Background

Patients with rare diseases face unique challenges in obtaining a diagnosis, appropriate medical care and access to support services. Whole genome and exome sequencing have increased identification of causal variants compared to single gene testing alone, with diagnostic rates of approximately 50% for inherited diseases, however integrated multi-omic analysis may further increase diagnostic yield. Additionally, multi-omic analysis can aid the explanation of genotypic and phenotypic heterogeneity, which may not be evident from single omic analyses.

Main body

This scoping review took a systematic approach to comprehensively search the electronic databases MEDLINE, EMBASE, PubMed, Web of Science, Scopus, Google Scholar, and the grey literature databases OpenGrey / GreyLit for journal articles pertaining to multi-omics and rare disease, written in English and published prior to the 30th December 2018. Additionally, The Cancer Genome Atlas publications were searched for relevant studies and forward citation searching / screening of reference lists was performed to identify further eligible articles. Following title, abstract and full text screening, 66 articles were found to be eligible for inclusion in this review. Of these 42 (64%) were studies of multi-omics and rare cancer, two (3%) were studies of multi-omics and a pre-cancerous condition, and 22 (33.3%) were studies of non-cancerous rare diseases. The average age of participants (where known) across studies was 39.4 years. There has been a significant increase in the number of multi-omic studies in recent years, with 66.7% of included studies conducted since 2016 and 33% since 2018. Fourteen combinations of multi-omic analyses for rare disease research were returned spanning genomics, epigenomics, transcriptomics, proteomics, phenomics and metabolomics.

Conclusions

This scoping review emphasises the value of multi-omic analysis for rare disease research in several ways compared to single omic analysis, ranging from the provision of a diagnosis, identification of prognostic biomarkers, distinct molecular subtypes (particularly for rare cancers), and identification of novel therapeutic targets. Moving forward there is a critical need for collaboration of multi-omic rare disease studies to increase the potential to generate robust outcomes and development of standardised biorepository collection and reporting structures for multi-omic studies.
Copeptin as a marker of outcome after cardiac arrest: a sub-study of the TTM trial
Authors: Düring Joachim , Annborn Martin , Cronberg Tobias , Dankiewicz Josef , Devaux Yvan , Hassager Christian , Horn Janneke , Kjaergaard Jesper , Kuiper Michael , Nikoukhah Homa Rafi , Stammet Pascal , Undén Johan , Wanscher Michael Jaeger , Wise Matt , Friberg Hans , Nielsen Niklas
Published: April 2020

Background

Arginine vasopressin has complex actions in critically ill patients, involving vasoregulatory status, plasma volume, and cortisol levels. Copeptin, a surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest.

Methods

Serial blood samples were collected at 24, 48, and 72 h as part of the target temperature management at 33 °C versus 36 °C after cardiac arrest trial, an international multicenter randomized trial where unconscious survivors after out-of-hospital cardiac arrest were allocated to an intervention of 33 or 36 °C for 24 h. Primary outcome was 30-day survival with secondary endpoints circulatory cause of death and cardiovascular deterioration composite; in addition, we examined the correlation with extended the cardiovascular sequential organ failure assessment (eCvSOFA) score.

Results

Six hundred ninety patients were included in the analyses, of whom 203 (30.3%) developed cardiovascular deterioration within 24 h, and 273 (39.6%) died within 30 days. Copeptin measured at 24 h was found to be independently associated with 30-day survival, hazard ratio 1.17 [1.06–1.28], p = 0.001; circulatory cause of death, odds ratio 1.03 [1.01–1.04], p = 0.001; and cardiovascular deterioration composite, odds ratio of 1.05 [1.02–1.08], p < 0.001. Copeptin at 24 h was correlated with eCvSOFA score with rho 0.19 [0.12–0.27], p < 0.001.

Conclusion

Copeptin is an independent marker of severity of the post cardiac arrest syndrome, partially related to circulatory failure.

Trial registration

Clinical Trials, NCT01020916. Registered November 26, 2009.
CCMetagen: comprehensive and accurate identification of eukaryotes and prokaryotes in metagenomic data
Authors: Marcelino Vanessa R. , Clausen Philip T. L. C. , Buchmann Jan P. , Wille Michelle , Iredell Jonathan R. , Meyer Wieland , Lund Ole , Sorrell Tania C. , Holmes Edward C.
Published: April 2020

There is an increasing demand for accurate and fast metagenome classifiers that can not only identify bacteria, but all members of a microbial community. We used a recently developed concept in read mapping to develop a highly accurate metagenomic classification pipeline named CCMetagen. The pipeline substantially outperforms other commonly used software in identifying bacteria and fungi and can efficiently use the entire NCBI nucleotide collection as a reference to detect species with incomplete genome data from all biological kingdoms. CCMetagen is user-friendly, and the results can be easily integrated into microbial community analysis software for streamlined and automated microbiome studies.
Effect of nutritional interventions on discharged older patients: study protocol for a randomized controlled trial
Authors: Munk Tina , Svendsen Jonas Anias , Knudsen Anne Wilkens , Østergaard Tanja Bak , Beck Anne Marie
Published: April 2020

Background

During hospitalization, many older patients are at nutritional risk or malnourished, and their nutritional condition is often further impaired during hospitalization. After discharge, a “nutrition gap” often occurs in which the patient does not receive enough nutrition to ensure an optimal recovery.

Methods

The study is a randomized controlled study ongoing over 112 days. At discharge, the intervention group receives guidance from a clinical dietitian, and an individualized nutrition plan is made. The dietitian will perform telephone follow-up after 4 and 30 days. It will also be possible for the participant, the participant’s relatives, or the participant’s municipality to contact the dietitian if nutritional questions arise. At the time of discharge, the intervention group will receive a package containing foods and drinks that will cover their nutritional needs on the first day after discharge. They will also receive a goodie bag containing samples of protein-rich, milk-based drinks. Data are collected on quality of life, appetite, physical function, dietary intake, weight, height, energy and protein needs, and experience of discharge and cooperation with the municipality. Information about nutrition status will be sent to the municipality so that the municipality can take over nutritional treatment. The control group receives a standard treatment.

Discussion

This study is the first to combine previously successful single nutritional interventions into a multimodal intervention whose aim is to obtain an effect on patient-related outcomes. We hope that the results will prove beneficial and help to ensure the cross-sector quality of nutritional support to older patients.

Trial registration

ClinicalTrials.gov, NCT03488329. April 5, 2018.
Peer support during in vivo exposure homework to reverse attrition from prolonged exposure therapy for posttraumatic stress disorder (PTSD): description of a randomized controlled trial
Authors: Hernandez-Tejada Melba A. , Muzzy Wendy , Price Matthew , Hamski Stephanie , Hart Stephanie , Foa Edna , Acierno Ron
Published: April 2020

Background

Effective treatments for posttraumatic stress disorder (PTSD) (e.g., prolonged exposure (PE); cognitive processing therapy (CPT)) exist and are widely adopted by the Departments of Veterans Affairs (VA) and Defense (DoD). Unfortunately, dropout from these treatments regularly exceeds 30%. However, in a recent survey of patients who dropped out of PE, approximately half indicated a greater likelihood of completion if a peer who had completed treatment were available to help with the in vivo exposure homework.

Methods

We will use a between-groups randomized controlled design with repeated assessment at baseline, post treatment, and 3- and 6-month follow-up across measures of PTSD, depression, and functioning with 150 veterans who have indicated that they intend to drop out of treatment. Participants will be randomly assigned to one of two PE + Peer Support conditions: (1) a peer will offer support directly during in vivo exposure homework for 3–4 weeks; vs (2) a peer will call weekly for 3–4 weeks to offer general support and to check in on treatment progress.

Discussion

The present study was designed to test the hypothesis that dropout from exposure-based PTSD treatment may be mitigated by using peers as support agents directly during PE in vivo homework experiences. Specifically, we intend to determine: whether patients who have dropped out of PE and are offered the “in vivo peer” adjunctive component to PE therapy will (1) return and complete treatment and (2) evince reduced PTSD symptomatology, compared to the same PE treatment, but with general peer support more reflective of current VA practices.

Trial registration

This study protocol is approved and information is available at ClinicalTrials.gov, ID: NCT03485391. Registered on 2 April 2018.