bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and disease predisposition of p.A91V perforin in an aged population of European ancestry
Authors: Voskoboinik Ilia , Lacaze Paul , Jang Helena Sung-In , Flinsenberg Thijs , Fernando Suran L. , Kerridge Ian , Riaz Moeen , Sebra Robert , Thia Kevin , Noori Taherah , Schadt Eric E. , McNeil John J. , Trapani Joseph A.
Published: January 2020

In a population-based analysis including a large database restricted to patients over age 70, the authors demonstrate that the A91V polymorphism in the familial hemophagocytic lymphohistiocytosis–related gene is a nonpathological polymorphism that confers no increase in cancer, death, or immunopathology.
Large-Area and Patternable Nano-Dot Array from Electrolysis of ITO Film for Surface-Enhanced Raman Spectroscopy
Authors: Lu Han , Han Gengxin , Cao Jieping , Jin Mingliang , Ma Qilin , Akinoglu Eser Metin , Wang Xin , Nian Li , Zhou Guofu , Shui Lingling
Published: January 2020

Fabrication of large-area devices with patternable nanostructures is important for practical applications in optical or electrical devices. In this work, we describe an easy and environment-friendly method for preparing large-area nano-dot (ND) arrays via the electrolytic reaction of a metal oxide film. NDs with various size and morphology can be obtained by adjusting the applied voltage, electrolysis time, and the film thickness of the indium tin oxide (ITO) layer. High-density NDs with size of 50–60 nm can be obtained by electrolysis of a 25-nm-thick ITO film at 150 V for 1.5 min under a water droplet medium, which have been applied for surface-enhanced Raman spectroscopy (SERS) after depositing a thin layer of silver. The SERS substrate with optimized ND structure exhibits sensitive detection of Rhodamine 6G (R6G) with detection limit down to 5 × 10-12 M. The enhancement factors (EFs) of 1.12 × 106 and 6.79 × 105 have been achieved for characterization of 4-methylbenzenethiol (4-MBT) and R6G, respectively. With an additional photolithographic step, multiple areas of ND arrays can be created on one substrate, enabling simultaneous detection of various samples containing different molecules at once experiment. Such a method is quick, easy, patternable, and environment-friendly, being suitable for on-site quick and synchronous determination of various molecules for applications in point-of-care, environmental monitoring, and airport security fields.
The impact of various seed, accessibility and interaction constraints on sRNA target prediction- a systematic assessment
Authors: Raden Martin , Müller Teresa , Mautner Stefan , Gelhausen Rick , Backofen Rolf
Published: January 2020

Background

Seed and accessibility constraints are core features to enable highly accurate sRNA target screens based on RNA-RNA interaction prediction. Currently, available tools provide different (sets of) constraints and default parameter sets. Thus, it is hard to impossible for users to estimate the influence of individual restrictions on the prediction results.

Results

Here, we present a systematic assessment of the impact of established and new constraints on sRNA target prediction both on a qualitative as well as computational level. This is done exemplarily based on the performance of IntaRNA, one of the most exact sRNA target prediction tools. IntaRNA provides various ways to constrain considered seed interactions, e.g. based on seed length, its accessibility, minimal unpaired probabilities, or energy thresholds, beside analogous constraints for the overall interaction. Thus, our results reveal the impact of individual constraints and their combinations.

Conclusions

This provides both a guide for users what is important and recommendations for existing and upcoming sRNA target prediction approaches.We show on a large sRNA target screen benchmark data set that only by altering the parameter set, IntaRNA recovers 30% more verified interactions while becoming 5-times faster. This exemplifies the potential of seed, accessibility and interaction constraints for sRNA target prediction.
Deep neural networks for human microRNA precursor detection
Authors: Zheng Xueming , Fu Xingli , Wang Kaicheng , Wang Meng
Published: January 2020

Background

MicroRNAs (miRNAs) play important roles in a variety of biological processes by regulating gene expression at the post-transcriptional level. So, the discovery of new miRNAs has become a popular task in biological research. Since the experimental identification of miRNAs is time-consuming, many computational tools have been developed to identify miRNA precursor (pre-miRNA). Most of these computation methods are based on traditional machine learning methods and their performance depends heavily on the selected features which are usually determined by domain experts. To develop easily implemented methods with better performance, we investigated different deep learning architectures for the pre-miRNAs identification.

Results

In this work, we applied convolution neural networks (CNN) and recurrent neural networks (RNN) to predict human pre-miRNAs. We combined the sequences with the predicted secondary structures of pre-miRNAs as input features of our models, avoiding the feature extraction and selection process by hand. The models were easily trained on the training dataset with low generalization error, and therefore had satisfactory performance on the test dataset. The prediction results on the same benchmark dataset showed that our models outperformed or were highly comparable to other state-of-the-art methods in this area. Furthermore, our CNN model trained on human dataset had high prediction accuracy on data from other species.

Conclusions

Deep neural networks (DNN) could be utilized for the human pre-miRNAs detection with high performance. Complex features of RNA sequences could be automatically extracted by CNN and RNN, which were used for the pre-miRNAs prediction. Through proper regularization, our deep learning models, although trained on comparatively small dataset, had strong generalization ability.
Fruit syndromes in Viburnum: correlated evolution of color, nutritional content, and morphology in bird-dispersed fleshy fruits
Authors: Sinnott-Armstrong Miranda A. , Lee Chong , Clement Wendy L. , Donoghue Michael J.
Published: January 2020

Premise

A key question in plant dispersal via animal vectors is where and why fruit colors vary between species and how color relates to other fruit traits. To better understand the factors shaping the evolution of fruit color diversity, we tested for the existence of syndromes of traits (color, morphology, and nutrition) in the fruits ofViburnum. We placed these results in a larger phylogenetic context and reconstructed ancestral states to assess howViburnumfruit traits have evolved across the clade.

Results

We find that blueViburnumfruits are not very juicy, and have high lipid content and large, round endocarps surrounded by a small quantity of pulp. Red fruits display the opposite suite of traits: they are very juicy with low lipid content and smaller, flatter endocarps. The ancestralViburnumfruit may have gone through a sequence of color changes before maturation (green to yellow to red to black), though our reconstructions are equivocal. In one major clade ofViburnum(Nectarotinus), fruits mature synchronously with reduced intermediate color stages. Most transitions between fruit colors occurred in this synchronously fruiting clade.

Conclusions

It is widely accepted that fruit trait diversity has primarily been driven by the differing perceptual abilities of bird versus mammal frugivores. Yet within a clade of largely bird-dispersed fruits, we find clear correlations between color, morphology, and nutrition. These correlations are likely driven by a shift from sequential to synchronous development, followed by diversification in color, nutrition, and morphology. A deeper understanding of fruit evolution within clades will elucidate the degree to which such syndromes structure extant fruit diversity.
Differential expression of microRNAs in tomato leaves treated with different light qualities
Authors: Dong Fei , Wang Chuanzeng , Dong Yuhui , Hao Shuqin , Wang Lixia , Sun Xiudong , Liu Shiqi
Published: January 2020

Background

Light is the main source of energy and, as such, is one of the most important environmental factors for plant growth, morphogenesis, and other physiological responses. MicroRNAs (miRNAs) are endogenous non-coding RNAs that contain 21–24 nucleotides (nt) and play important roles in plant growth and development as well as stress responses. However, the role of miRNAs in the light response is less studied. We used tomato seedlings that were cultured in red light then transferred to blue light for 2 min to identify miRNAs related to light response by high-throughput sequencing.

Results

A total of 108 known miRNAs and 141 predicted novel miRNAs were identified in leaf samples from tomato leaves treated with the different light qualities. Among them, 15 known and 5 predicted novel miRNAs were differentially expressed after blue light treatment compared with the control (red light treatment). KEGG enrichment analysis showed that significantly enriched pathways included zeatin biosynthesis (ko00908), homologous recombination (ko03440), and plant hormone signal transduction (ko04075). Zeatin biosynthesis and plant hormone signal transduction are related to plant hormones, indicating that plant hormones play important roles in the light response.

Conclusion

Our results provide a theoretical basis for further understanding the role of miRNAs in the light response of plants.
Comparative transcriptomics of stem bark reveals genes associated with bast fiber development in Boehmeria nivea L. gaud (ramie)
Authors: Xie Jiyong , Li Jiaqi , Jie Yucheng , Xie Deyu , Yang Di , Shi Huazhong , Zhong Yingli
Published: January 2020

Background

Boehmeria nivea L. Gaud (Ramie) produces one of the longest natural fibers in nature. The bark of ramie mainly comprises of the phloem tissue of stem and is the raw material for fiber. Therefore, identifying the molecular regulation of phloem development is important for understanding of bast fiber biosynthesis and improvement of fiber quality in ramie.

Results

In this study, we collected top bud (TB), bark from internode elongating region (ER) and bark from internode fully elongated region (FER) from the ramie variety Zhongzhu No. 1. Histological study indicated that these samples contain phloem tissues at different developmental and maturation stages, with a higher degree of maturation of phloem tissue in FER. RNA sequencing (RNA-seq) was performed and de novo transcriptome was assembled. Unigenes and differentially expressed genes (DEGs) in these three samples were identified. The analysis of DEGs by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed clear differences in gene expression between ER and FER. Some unigenes involved in secondary cell wall biosynthesis were up-regulated in both ER and FER, while unigenes for some cell wall components or cell wall modifications showed differential expression between ER and FER. In addition, the ethylene respond factors (ERFs) in the ethylene signaling pathway were up-regulated in FER, and ent-kaurenoic acid oxidase (KAO) and GA 20-oxidase (GA20ox) for gibberellins biosynthesis were up-regulated while GA 2-oxidase (GA2ox) for gibberellin inactivation was down-regulated in FER.

Conclusions

Both morphological study and gene expression analysis supported a burst of phloem and vascular developmental processes during the fiber maturation in the ramie stem, and ethylene and gibberellin are likely to be involved in this process. Our findings provide novel insights into the phloem development and fiber maturation in ramie, which could be useful for fiber improvement in ramie and other fiber crops.
GWAS and fine-mapping of livability and six disease traits in Holstein cattle
Authors: Freebern Ellen , Santos Daniel J. A. , Fang Lingzhao , Jiang Jicai , Parker Gaddis Kristen L. , Liu George E. , VanRaden Paul M. , Maltecca Christian , Cole John B. , Ma Li
Published: January 2020

Background

Health traits are of significant economic importance to the dairy industry due to their effects on milk production and associated treatment costs. Genome-wide association studies (GWAS) provide a means to identify associated genomic variants and thus reveal insights into the genetic architecture of complex traits and diseases. The objective of this study is to investigate the genetic basis of seven health traits in dairy cattle and to identify potential candidate genes associated with cattle health using GWAS, fine mapping, and analyses of multi-tissue transcriptome data.

Results

We studied cow livability and six direct disease traits, mastitis, ketosis, hypocalcemia, displaced abomasum, metritis, and retained placenta, using de-regressed breeding values and more than three million imputed DNA sequence variants. After data edits and filtering on reliability, the number of bulls included in the analyses ranged from 11,880 (hypocalcemia) to 24,699 (livability). GWAS was performed using a mixed-model association test, and a Bayesian fine-mapping procedure was conducted to calculate a posterior probability of causality to each variant and gene in the candidate regions. The GWAS detected a total of eight genome-wide significant associations for three traits, cow livability, ketosis, and hypocalcemia, including the bovine Major Histocompatibility Complex (MHC) region associated with livability. Our fine-mapping of associated regions reported 20 candidate genes with the highest posterior probabilities of causality for cattle health. Combined with transcriptome data across multiple tissues in cattle, we further exploited these candidate genes to identify specific expression patterns in disease-related tissues and relevant biological explanations such as the expression of Group-specific Component (GC) in the liver and association with mastitis as well as the Coiled-Coil Domain Containing 88C (CCDC88C) expression in CD8 cells and association with cow livability.

Conclusions

Collectively, our analyses report six significant associations and 20 candidate genes of cattle health. With the integration of multi-tissue transcriptome data, our results provide useful information for future functional studies and better understanding of the biological relationship between genetics and disease susceptibility in cattle.
Transcriptome-wide map of m6A circRNAs identified in a rat model of hypoxia mediated pulmonary hypertension
Authors: Su Hua , Wang Guowen , Wu Lingfang , Ma Xiuqing , Ying Kejing , Zhang Ruifeng
Published: January 2020

Background

Hypoxia mediated pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m6A-modified. The abundance of circRNAs was influenced by m6A. Furthermore, the significance of m6A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m6A circRNAs in HPH.

Results

Differentially expressed m6A abundance was detected in lungs of HPH rats. M6A abundance in circRNAs was significantly reduced in hypoxia in vitro. M6A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m6A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M6A circXpo6 and m6A circTmtc3 were firstly identified to be downregulated in HPH.

Conclusion

Our study firstly identified the transcriptome-wide map of m6A circRNAs in HPH.

M6A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m6A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m6A circRNAs for HPH should be further validated.
Gene regulatory response to hyposalinity in the brown seaweed Fucus vesiculosus
Authors: Rugiu Luca , Panova Marina , Pereyra Ricardo Tomás , Jormalainen Veijo
Published: January 2020

Background

Rockweeds are among the most important foundation species of temperate rocky littoral shores. In the Baltic Sea, the rockweedFucus vesiculosusis distributed along a decreasing salinity gradient from the North Atlantic entrance to the low-salinity regions in the north-eastern margins, thus, demonstrating a remarkable tolerance to hyposalinity. The underlying mechanisms for this tolerance are still poorly understood. Here, we exposedF. vesiculosusfrom two range-margin populations to the hyposaline (2.5 PSU - practical salinity unit) conditions that are projected to occur in the region by the end of this century as a result of climate change. We used transcriptome analysis (RNA-seq) to determine the gene expression patterns associated with hyposalinity acclimation, and examined the variation in these patterns between the sampled populations.

Results

Hyposalinity induced different responses in the two populations: in one, only 26 genes were differentially expressed between salinity treatments, while the other population demonstrated up- or downregulation in 3072 genes. In the latter population, the projected future hyposalinity induced an acute response in terms of antioxidant production. Genes associated with membrane composition and structure were also heavily involved, with the upregulation of fatty acid and actin production, and the downregulation of ion channels and alginate pathways. Changes in gene expression patterns clearly indicated an inhibition of the photosynthetic machinery, with a consequent downregulation of carbohydrate production. Simultaneously, energy consumption increased, as revealed by the upregulation of genes associated with respiration and ATP synthesis. Overall, the genes that demonstrated the largest increase in expression were ribosomal proteins involved in translation pathways. The fixation rate of SNP:s was higher within genes responding to hyposalinity than elsewhere in the transcriptome.

Conclusions

The high fixation rate in the genes coding for salinity acclimation mechanisms implies strong selection for them. The among-population differentiation that we observed in the transcriptomic response to hyposalinity stress suggests that populations ofF. vesiculosusmay differ in their tolerance to future desalination, possibly as a result of local adaptation to salinity conditions within the Baltic Sea. These results emphasise the importance of considering interspecific genetic variation when evaluating the consequences of environmental change.
Comparative transcriptomic and metabolic analysis of wild and domesticated wheat genotypes reveals differences in chemical and physical defense responses against aphids
Authors: Batyrshina Zhaniya S. , Yaakov Beery , Shavit Reut , Singh Anuradha , Tzin Vered
Published: January 2020

Background

Young wheat plants are continuously exposed to herbivorous insect attack. To reduce insect damage and maintain their growth, plants evolved different defense mechanisms, including the biosynthesis of deterrent compounds named benzoxazinoids, and/or trichome formation that provides physical barriers. It is unclear whether both of these mechanisms are equally critical in providing an efficient defense for wheat seedlings against aphids—an economically costly pest in cereal production.

Results

In this study, we compared the transcriptome, metabolome, benzoxazinoids, and trichome density of three selected wheat genotypes, with a focus on differences related to defense mechanisms. We chose diverse wheat genotypes: two tetraploid wheat genotypes, domesticated durum ‘Svevo’ and wild emmer ‘Zavitan,’ and one hexaploid bread wheat, ‘Chinese Spring.’ The full transcriptomic analysis revealed a major difference between the three genotypes, while the clustering of significantly different genes suggested a higher similarity between the two domesticated wheats than between either and the wild wheat. A pathway enrichment analysis indicated that the genes associated with primary metabolism, as well as the pathways associated with defense such as phytohormones and specialized metabolites, were different between the three genotypes. Measurement of benzoxazinoid levels at the three time points (11, 15, and 18 days after germination) revealed high levels in the two domesticated genotypes, while in wild emmer wheat, they were below detection level. In contrast to the benzoxazinoid levels, the trichome density was dramatically higher in the wild emmer than in the domesticated wheat. Lastly, we tested the bird cherry-oat aphid’s (Rhopalosiphum padi) performance and found that Chinese Spring is more resistant than the tetraploid genotypes.

Conclusions

Our results show that benzoxazinoids play a more significant defensive role than trichomes. Differences between the abundance of defense mechanisms in the wild and domesticated plants were observed in which wild emmer possesses high physical defenses while the domesticated wheat genotypes have high chemical defenses. These findings provide new insights into the defense adaptations of wheat plants against aphids.
Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats
Authors: Sepehrinezhad Ali , Dehghanian Amirreza , Rafati Ali , Ketabchi Farzaneh
Published: January 2020

Background

Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases.

Methods

Female Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O2 50%) and hypoxia (O2 10%). Besides, we assessed blood parameters and liver histology.

Results

Liver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group.

Conclusion

Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.
Value of the Barthel scale in prognostic prediction for patients with cerebral infarction
Authors: Li Qun-Xi , Zhao Xiao-Jing , Wang Yan , Wang Da-Li , Zhang Jiang , Liu Tie-Jun , Peng Yan-Bo , Fan Hai-Yan , Zheng Fu-Xia
Published: January 2020

Background

This study aims to evaluate the ADL(activity of daily living) of patients with acute cerebral infarction through BI scoring, in order to observe its predictive value in the prognosis of these patients.

Methods

According to the inclusion and exclusion criteria, patients with acute anterior circulation cerebral infarction were included in the present study. Then, the BI scoring was analyzed through five grades, in order to further investigate the dose-response relationship between BI scoring and mortality risk in patients with cerebral infarction. The receiver operating characteristic (ROC) curves for BI-scored patients were drawn, and the predictive authenticity of the Barthel scale in prognostic prediction for patients with cerebral infarction was estimated.

Results

The difference in BI scores between the survival group and death group were statistically significant (t = 10.029, P < 0.05), in which the score was lower in the death group than in the survival group. According to the linear trend ×2-test, the decrease in BI score indicates an increase in mortality risk in patients with cerebral infarction. The area under the curve (AUC) of the ROC curve was 0.794 with a P–value of < 0.05.

Conclusion

BI scoring is a highly valuable scoring system for the prognostic prediction of patients with acute cerebral infarction.
ABC-tool reinvented: development of a disease-specific ‘Assessment of Burden of Chronic Conditions (ABCC)-tool’ for multiple chronic conditions
Authors: Boudewijns Esther A. , Claessens Danny , van Schayck Onno C. P. , Keijsers Lotte C. E. M. , Salomé Philippe L. , in ‘t Veen Johannes C. C. M. , Bilo Henk J. G. , Gidding-Slok Annerika H. M.
Published: January 2020

Background

Numerous instruments have been developed to assess patient reported outcomes; most approaches however focus on a single condition. With the increasing prevalence of multimorbidity, this might no longer be appropriate. Moreover, a more comprehensive approach that facilitates shared decision making and stimulates self-management is most likely more valuable for clinical practice than a questionnaire alone. This study aims to transform the Assessment of Burden of Chronic Obstructive Pulmonary Disease (COPD) (ABC)-tool into the Assessment of Burden of Chronic Conditions (ABCC)-tool for COPD, asthma, and diabetes mellitus type 2 (DM2). The tool consists of a scale, a visualisation of the outcomes, and treatment advice.

Methods

Requirements for the tool were formulated. Questionnaires were developed based on a literature study of existing questionnaires, clinical guidelines, interviews with patients and healthcare providers, and input from an expert group. Cut-off points and treatment advice were determined to display the results and to provide practical recommendations.

Results

The ABCC-scale consists of a generic questionnaire and disease-specific questionnaires, which can be combined into a single individualized questionnaire for each patient. Results are displayed in one balloon chart, and each domain includes practical recommendations.

Conclusions

The ABCC-tool is expected to facilitate conversations between a patient and a healthcare provider, and to help formulate treatment plans and care plans with personalised goals. By facilitating an integrated approach, this instrument can be applied in a variety of circumstances and disease combinations.
Ultrasonography in assessing suspected bone fractures: a cross-sectional survey amongst German general practitioners
Authors: Schmid Gordian Lukas , Kühnast Beatrice , Heise Marcus , Deutsch Tobias , Frese Thomas
Published: January 2020

Background

Over the last two decades, ultrasonography (US) has been shown to be an accurate tool for the diagnosis of suspected bone fractures; however, the integration of this application of US into routine care and outpatient settings needs to be explored. In this study, we surveyed German general practitioners (GPs) to assess their knowledge, attitudes, and utilization of US for the diagnosis of suspected fractures.

Methods

Notification of the study, a self-designed questionnaire, and a reminder were mailed to 600 randomly selected GPs in Saxony and Saxony-Anhalt.

Results

The response rate was 47.7% (n = 286), and respondents did not differ from the population of all GPs in respect to sex and practice type. Among GPs surveyed, 48.6% used an US device in their practice. On average, GPs diagnosed six patients with suspected fractures per month, yet only 39.3% knew about the possibility of ultrasonographic fracture diagnosis, and only 4.3% of GPs using US applied it for this purpose. Among participants, 71.9% believed that US is inferior to conventional X-rays for the diagnosis of bony injuries. Users of US were better informed of and more commonly used US for fracture diagnosis compared to non-users.

Conclusion

The need to rule out possible fractures frequently arises in general practice, and US devices are broadly available. Further efforts are needed to improve the knowledge and attitudes of GPs regarding the accuracy of US for fracture diagnosis. Multicenter controlled trials could explore the safety, usefulness, and effectiveness of this still seldom used diagnostic approach for suspected fractures.
Twenty-five years on: revisiting Bosnia and Herzegovina after implementation of a family medicine development program
Authors: Hodgetts Geoffrey , Brown Glenn , Batić-Mujanović Olivera , Gavran Larisa , Jatić Zaim , Račić Maja , Tešanović Gordana , Zahilić Amra , Martin Mary , Birtwhistle Richard
Published: January 2020

Background

The wars that ravaged the former Socialist Federal Republic of Yugoslavia in the 1990’s resulted in the near destruction of the healthcare system, including education of medical students and the training of specialist physicians. In the latter stages of the war, inspired by Family Medicine programs in countries such as Canada, plans to rebuild a new system founded on a strong primary care model emerged. Over the next fifteen years, the Queen’s University Family Medicine Development Program in Bosnia and Herzegovina played an instrumental role in rebuilding the primary care system through educational initiatives at the undergraduate, residency, Masters, PhD, and continuing professional development levels. Changes were supported by new laws and regulations to insure sustainability. This study revisited Bosnia and Herzegovina (B-H) 8-years after the end of the program to explore the impact of initiatives through understanding the perspectives and experiences of individuals at all levels of the primary care system from students, deans of medical schools, Family Medicine residents, practicing physicians, Health Center Directors and Association Leaders.

Methods

Qualitative exploratory design using purposeful sampling. Semi-structured interviews and focus groups with key informants were conducted in English or with an interpreter as needed and audiotaped. Transcripts and field notes were analyzed using an interpretative phenomenological approach to identify major themes and subthemes.

Results

Overall, 118 participants were interviewed. Three major themes and 9 subthemes were identified including (1) The Development of Family Medicine Education, (subthemes: establishment of departments of family medicine, undergraduate medical curriculum change), (2) Family Medicine as a Discipline (Family Medicine specialization, academic development, and Family Medicine Associations), and (3) Health Care System Issues (continuity of care, comprehensiveness of care, practice organization and health human resources).

Conclusions

Despite the impact of years of war and the challenges of a complex and unstable postwar environment, initiatives introduced by the Queen’s Program succeeded in establishing sustainable changes, allowing Family Medicine in B-H to continue to adapt without abandoning its strong foundations. Despite the success of the program, the undervaluing of Primary Care from a human resource and health finance perspective presents ongoing threats to the system.
RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats
Authors: Feng Yanhu , Han Zhijian , Feng Zedong , Wang Bofang , Cheng Huijuan , Yang Luxi , Li Yangbing , Gu Baohong , Li Xuemei , Li Yahao , Li Yumin , Wang Chen , Chen Hao
Published: January 2020

Background

The anti-immunological rejection therapy for small-for-size syndrome (SFSS) after live donor liver transplantation (LDLT) play a central role in keeping graft survival. The hepatocyte number and grafts function has undergone real-time changes with the proliferation and apoptosis of the grafts after reperfusion. Lacking an accurate and effective treatment regiments or indicators to guide the use of immunosuppressive drugs in SFS liver transplantation has made immunotherapy after SFS liver transplantation an urgent problem to be solved. Herein, we established small-for-size (SFS) and normal size liver transplantation model in rats to explore the effective indicators in guiding immunotherapy, to find an effective way for overcoming SFSS.

Methods

Lewis rats (donors) and BN rats (recipients) were used to mimic allograft liver transplantation and treated with tacrolimus. Local graft immune response was analyzed through haematoxylin and eosin and immunohistochemistry. Flow cytometry was used to assess the overall immune status of recipient. The pharmacokinetics mechanism of immunosuppressive drugs was explored through detecting CYP3A2 expression at mRNA level and protein levels.

Results

The results showed the local immune reaction of SFS grafts and systemic immune responses of recipient were significantly increased compared with those in normal size grafts and their recipient at four days after liver transplantation. Regression equation was used to regulate the tacrolimus dose which not only controlled tacrolimus serum concentration effectively but alleviated liver damage and improved survival rate.

Conclusions

This study showed that AST level and tacrolimus serum concentrations are effective indicators in guiding immunotherapy. Regression equation (TD = − 0.494TC-0.0035AST + 260.487) based on AST and tacrolimus serum concentration can be used as a reference for adjustment of immunotherapy after SFS liver transplantation, which is applicable in clinical practice.
A new grounded theory model of sexual adjustment to HIV: facilitators of sexual adjustment and recommendations for clinical practice
Authors: Huntingdon Ben , Sharpe Louise , de Wit John , Duracinsky Martin , Juraskova Ilona
Published: January 2020

Background

Life expectancy of people living with HIV (PLWH) is increasing. Effective biomedical prevention methods (treatment as prevention and preexposure prophylaxis) are being widely implemented in high-income nations. Therefore, research into quality of life, including sexual adjustment, is of increasing importance to HIV care. Yet, sexual adjustment of PLWH has been neglected in past research. We propose a new model of sexual adjustment to HIV which explores the dynamic process, facilitators and barriers characterising sexual life of PLWH overtime.

Method

Thirty PLWH (19 male, 11 female) recruited from two HIV treatment centres as well as community groups, completed semi-structured interviews which were audio-recorded and transcribed verbatim for analysis using grounded theory.

Results

The model of sexual adjustment to HIV is the first to establish how undue fears of transmission of HIV during sex and/or fear of rejection by sexual partners determine initial sexual behaviour after diagnosis and also sexual adjustment over time. Within the model, sexual adjustment to HIV is facilitated by factors which assist PLWH to overcome such fears, including: partner acceptance, peer, community and health professional support, and accurate knowledge of risk of transmission including of undetectable viral load and pre-exposure prophylaxis. Adjustment is inhibited when undue fears of transmission and of rejection persist long term, resulting in maladaptive behaviours to cope with such fears including avoidance of sex and problematic drug and alcohol use.

Conclusion

This model offers clear directions for promoting sexual adjustment to HIV. Health professionals should: (a) assess and intervene for sexual quality of life (not just risk) among PLWH; (b) be aware that serosorting facilitates adjustment in the short to medium term, but may interfere with adjustment long-term, (c) promote opportunities for positive connection between PLWH, and (d) intervene directly with PLWH and HIV negative sexual partners to promote accurate risk of transmission knowledge, including how this applies to their own sexual practices, and whether they are experiencing undue fear of transmission over time.
Prevalence of diarrhoea and associated risk factors among children under five years old in Pader District, northern Uganda
Authors: Omona Stephen , Malinga Geoffrey M. , Opoke Robert , Openy Geoffrey , Opiro Robert
Published: January 2020

Background

Diarrhoea remains a major cause of morbidity and mortality in children under 5 years in sub-Saharan Africa. Of the three East African countries, Uganda has the worst mortality rate in children < 5 years, with 22% of these deaths attributed to diarrhoea. For proper planning and implementation of control, an understanding of the prevalence and determinants of the disease is crucial. This study assessed the prevalence of diarrhoea and related risk factors among children < 5 years in Pajule Subcounty, Pader District in northern Uganda.

Methods

A cross-sectional survey was conducted in April 2018, covering 244 randomly selected households having children < 5 years old in the study area. A semi-structured questionnaire was used to interview the households about diarrhoeal history in their children in the last 2 weeks preceding the survey, and on the risk factors predisposing children to diarrhoeal infections. Bivariate and multivariate logistic regression analyses with a 95% confidence interval and p < 0.05 was used to identify the risk factors associated with childhood diarrhoeal disease.

Results

We found a prevalence of diarrhoea of 29.1% [95% CI (23.7–35.0)] among children < 5 years in Pajule Subcounty during the 2 weeks preceding the survey. Use of unprotected water sources, age of child caretaker, child weaning time and family size had significant associations with diarrhoeal morbidity.

Conclusion

The prevalence of childhood diarrhoea among children < 5 years of age in rural settings of Pajule Subcounty was higher than the Ugandan national average. Use of unprotected water sources, age of child caretaker, child weaning time and family size were identified as predictors of diarrhoeal occurrence. These findings underscore the need for improving access to clean water and providing community health education as the best methods for fighting childhood diarrhoea in the study area.
Childhood neurodegeneration associated with a specific UBTF variant: a new case report and review of the literature
Authors: Bastos Filipa , Quinodoz Mathieu , Addor Marie-Claude , Royer-Bertrand Beryl , Fodstad Heidi , Rivolta Carlo , Poloni Claudia , Superti-Furga Andrea , Roulet-Perez Eliane , Lebon Sebastien
Published: January 2020

Background

A new monogenic neurodegenerative disease affecting ribosomal metabolism has recently been identified in association with a monoallelicUBTFputative gain of function variant (NM_001076683.1:c.628G>A, hg19). Phenotype is consistent among these probands with progressive motor, cognitive, and behavioural regression in early to middle childhood.

Case presentation

We report on a child with this monoallelicUBTFvariant who presented with progressive disease including regression, episodes of subacute deterioration during febrile illnesses and a remarkable EEG pattern with a transient pattern of semi-periodic slow waves.

Conclusions

This case further supports the phenotype-genotype correlation of neurodegeneration associated withUBTFc.628G>A. Moreover, it brings new insights into the clinical features and EEG that could possibly serve as diagnostic markers of this otherwise nonspecific phenotype.
Midwives’ engagement in smoking- and alcohol-prevention in prenatal care before and after the introduction of practice guidelines in Switzerland: comparison of survey findings from 2008 and 2018
Authors: Lemola Sakari , Gkiouleka Anna , Urfer-Maurer Natalie , Grob Alexander , Tritten Schwarz Katharina , Meyer-Leu Yvonne
Published: January 2020

Background

Evidence suggests that cigarette smoking and alcohol consumption during pregnancy negatively impacts fetal health. Health agencies across countries have developed specific guidelines for health professionals in perinatal care to strengthen their role in smoking and alcohol use prevention. One such example is the “Guideline on Screening and Counselling for prevention of cigarette smoking and alcohol consumption before, during, and after pregnancy” introduced by the Swiss Midwives Association in 2011. The current study assesses the changes in midwives’ engagement in smoking and alcohol use prevention before (2008) and after the introduction of the Guideline (2018). Further, the current study examines differences across regions (German vs. French speaking regions), graduation years (before and after the introduction of the Guideline) and different work settings (hospital vs. self-employed).

Methods

Survey data were collected in 2008 (n = 366) and in 2018 (n = 459). Differences in how midwives engaged in smoking and alcohol use prevention between 2008 and 2018 were assessed with chi-square tests, as were differences across German and French speaking regions, graduation years (before and after the introduction of the Guideline) and across different work settings (working in hospitals or as self-employed).

Results

An increase in midwives’ awareness of the risks of consuming even small quantities of cigarettes and alcohol for the unborn child between 2008 and 2018 is evident. Explaining the risks to pregnant women who smoke or use alcohol remained the most frequently reported prevention strategy. However, engagement with more extensive smoking and alcohol use preventive strategies across the whole course of pregnancy, such as assisting women in the elaboration of a plan to stop smoking/alcohol use, remained limited.

Conclusions

Seven years after its introduction, the effectiveness of the Guideline in increasing midwives’ engagement in smoking and alcohol use prevention appears limited despite midwives’ increased awareness.
Perinatal outcomes of infants with congenital limb malformations: an observational study from a tertiary referral center in Central Europe
Authors: Farr Alex , Wachutka Eva , Bettelheim Dieter , Windsperger Karin , Farr Sebastian
Published: January 2020

Background

Congenital limb malformations are rare, and their perinatal outcomes are not well described. This study analyzed the perinatal outcomes of infants with congenital limb malformations.

Methods

All infants with congenital limb malformations who underwent prenatal assessment and delivery at our tertiary referral center from 2004 through 2017 were retrospectively identified. Neonatal outcome parameters were assessed, and the predictors of worse perinatal outcomes were determined.

Results

One hundred twenty-four cases of congenital limb malformations were identified, of which 104 (83.9%) were analyzed. The upper limb was affected in 15 patients (14.4%), the lower limb in 49 (47.1%), and both limbs in 40 (38.5%) patients. A fetal syndrome was identified in 66 patients (63.5%); clubfoot and longitudinal reduction defects were the most frequent malformations. In total, 38 patients (36.5%) underwent termination, seven (6.7%) had stillbirth, and 59 (56.7%) had live-born delivery. Rates of preterm delivery and transfer to the Neonatal Intensive Care Unit were 42.4 and 25.4%, respectively. Localization of the malformation was a determinant of perinatal outcome (P = .006) and preterm delivery (P = .046).

Conclusions

Congenital limb malformations frequently occur bilaterally and are associated with poor perinatal outcomes, including high rates of stillbirth and preterm delivery. Multidisciplinary care and referral to a perinatal center are warranted.
Why do women assume a supine position when giving birth? The perceptions and experiences of postnatal mothers and nurse-midwives in Tanzania
Authors: Mselle Lilian Teddy , Eustace Lucia
Published: January 2020

Background

Before the advent of Western medicine in Tanzania, women gave birth in an upright position either by sitting, squatting or kneeling. Birthing women would hold ropes or trees as a way of gaining strength and stability in order to push the baby with sufficient force. Despite the evidence supporting the upright position as beneficial to the woman and her unborn child, healthcare facilities consistently promote the use of the supine position. The purpose of this study was to explore the perceptions and experiences of mothers and nurse-midwives regarding the use of the supine position during labour and delivery.

Methods

We used a descriptive qualitative design. We conducted seven semi-structured interviews with nurse-midwives and two focus group discussions with postnatal mothers who were purposively recruited for the study. Qualitative content analysis guided the analysis.

Results

Four themes emerged from mothers’ and midwives’ description of their experiences and perceptions of using supine position during childbirth. These were: women adopted the supine position as instructed by midwives; women experience of using alternative birthing positions; midwives commonly decide birthing positions for labouring women and supine position is the best-known birthing position.

Conclusion

Women use the supine position during childbirth because they are instructed to do so by the nurse-midwives. Nurse-midwives believe that the supine position is the universally known and practised birthing position, and prefer it because it provides flexibility for them to continuously monitor the progress of labour and assist delivery most efficiently. Mothers in this study had no other choice than to labour and deliver their babies in the supine position as instructed because they trusted midwives as skilled professionals who knew what was best given the condition of the mother and her baby.
Developmental risk among Aboriginal children living in urban areas in Australia: the Study of Environment on Aboriginal Resilience and Child Health (SEARCH)
Authors: Chando Shingisai , Craig Jonathan C. , Burgess Leonie , Sherriff Simone , Purcell Alison , Gunasekera Hasantha , Banks Sandra , Smith Natalie , Banks Emily , Woolfenden Sue
Published: January 2020

Background

Most Australian Aboriginal children are on track with their development, however, the prevalence of children at risk of or with a developmental or behavioural problem is higher than in other children. Aboriginal child development data mostly comes from remote communities, whereas most Aboriginal children live in urban settings. We quantified the proportion of participating children at moderate and high developmental risk as identified by caregivers’ concerns, and determined the factors associated with developmental risk among urban Aboriginal communities.

Methods

Study methods were co-designed and implemented with four participating urban Aboriginal Community Controlled Health Services in New South Wales, Australia, between 2008 and 2012. Caregiver-reported data on children < 8 years old enrolled in a longitudinal cohort study (Study of Environment on Aboriginal Resilience and Child Health: SEARCH) were collected by interview. The Parents’ Evaluation of Developmental Status (PEDS) was used to assess developmental risk through report of caregiver concerns. Odds ratios (OR) were calculated using multinomial logistic regression to investigate risk factors and develop a risk prediction model.

Results

Of 725 children in SEARCH with PEDS data (69% of eligible), 405 (56%) were male, and 336 (46%) were aged between 4.5 and 8 years. Using PEDS, 32% were at high, 28% moderate, and 40% low/no developmental risk. Compared with low/no risk, factors associated with high developmental risk in a mutually-adjusted model, with additional adjustment for study site, were male sex (OR 2.42, 95% confidence intervals 1.62–3.61), being older (4.5 to < 8 years versus < 3 years old, 3.80, 2.21–6.54), prior history of ear infection (1.95, 1.21–3.15), having lived in 4 or more houses versus one house (4.13, 2.04–8.35), foster care versus living with a parent (5.45, 2.32–12.78), and having a caregiver with psychological distress (2.40, 1.37–4.20).

Conclusion

In SEARCH, 40% of urban Aboriginal children younger than 8 years were at no or low developmental risk. Several factors associated with higher developmental risk were modifiable. Aboriginal community-driven programs to improve detection of developmental problems and facilitate early intervention are needed.