bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple method for in vitro preparation of natural killer cells from cord blood
Authors: Mu Yong Xu , Zhao Yu Xia , Li Bing Yao , Bao Hong Jing , Jiang Hui , Qi Xiao Lei , Bai Li Yun , Wang Yun Hong , Ma Zhi Jie , Wu Xiao Yun
Published: December 2019

Background

Cord Blood (CB) has been considered a promising source of natural killer (NK) cells for cellular immunotherapy. However, it is difficult to expand the large numbers of highly pure NK cells from CB without cell sorting and feeder cells/multiple cytokines. In this study, we try to develop a simple, safe and economical method for ex vivo expansion and purification of NK cells from CB without cell sorting and feeder cells/multiple cytokines.

Results

The large numbers (mean: 1.59 × 1010) of highly pure (≥90%) NK cells from CB could be obtained through interleukin-2, group A streptococcus and zoledronate stimulation of mononuclear cells using the 21-day culture approach. When compared to resting NK cells, expanded NK cells were a higher expression of activating receptors CD16, NKG2D, NKp30, NKp44, NKp46 and activating markers CD62L and CD69, while the inhibitory receptors, CD158a and CD158b remained largely unchanged. In addition, these cells showed a higher concentration of IFN-γ, TNF-α and GM-CSF secretion and cytotoxicity to K562 cells and acute myeloid leukemia targets than resting NK cells.

Conclusion

We develop a simple, safe and economical method to obtain high yield, purity, and functionality NK cells from CB without cell sorting and feeder cells/multiple cytokines.
Association of major dietary patterns and different metabolic phenotypes: a population-based study of northwestern Iran
Authors: Nikniaz Leila , Abbasalizad Farhangi Mahdieh , Tabrizi Jafar Sadegh , Nikniaz Zeinab
Published: December 2019

Background

Finding the relationship between the major dietary patterns and cardiometabolic phenotypes could be used for planning prevention programs based on the cultural and dietary habits to prevent transient from a metabolically healthy state to an unhealthy state. So, we aimed to assess the association between dietary patterns and cardiometabolic phenotypes in the northwestern population of Iran.

Method

In the present cross-sectional and population-based study, 504 adults sampled by cluster sampling in East-Azerbaijan, Iran. Factor analysis was used for determining the dietary pattern. Metabolic phenotypes were determined according to body mass index (BMI) cut–off point (25 kg/m2), and the presence of the metabolic syndrome. The independent sample t-test, one-way ANOVA, chi-square, and multinomial regression were used for statistical analysis.

Results

In both adjusted (OR: 2.24, 95% CI: 1.17, 4.31) and unadjusted models (OR: 3.14, 95% CI: 1.54, 5.42), the last tertile of the animal dietary pattern was associated with metabolically healthy obese (MHO) phenotypes. After adjusting, the last tertile of the animal dietary pattern was significantly associated with an increase of metabolically unhealthy obese (MUHO) phenotype (OR: 2.61, 95% CI: 1.18, 5.76).

Conclusion

In the present study, the animal dietary pattern was associated with MHO and MUHO phenotypes. It is suggested that some measures should be taken to strengthen nutrition education for the population and advocate a balanced diet to improve the condition.
Influence of different application protocols of universal adhesive system on the clinical behavior of Class I and II restorations of composite resin – a randomized and double-blind controlled clinical trial
Authors: Carvalho Andreia Assis , Leite Murillo Martins , Zago Jessica Karla Maia , Nunes Carla Aparecida Bernardes Costa Men , Barata Terezinha de Jesus Esteves , Freitas Gersinei Carlos de , Torres Érica Miranda de , Lopes Lawrence Gonzaga
Published: December 2019

Background

Multimode adhesives incorporate the versatility of adapting to various clinical situations by its capacity to be used in different protocols. This study aimed to evaluate the clinical behavior of composite resin direct restorations (Class I and II) performed with different universal dentin adhesive application protocols comparing adapted FDI and adapted USPHS criteria.

Methods

The current study is a randomized, double-blind, split-mouth, and convenience sample controlled clinical trial. The participants (age ≥ 18 years) had restorative need of Class I and/or II due to the presence of carious lesions and/or unsatisfactory restorations in at least three dental elements. Each participant received three application protocols for Scotchbond Universal adhesive (3M ESPE), one in each tooth to be restored: ER = etch-and-rinse + adhesive (n = 50); SEE = selective enamel etch + adhesive (n = 50) and SE = self-etch adhesive (n = 50). All teeth were restored in a similar way using Filtek™ Supreme composite resin (3M ESPE). Restorations were evaluated using the adapted FDI and adapted USPHS criteria, at baseline after 7 to 21 (12.02 ± 5.68) days (T1; n = 50 per group) and after 12 to 20 (15.8 ± 2.7) months (T2; n = 46 per group) by two previously calibrated evaluators (Kappa > 0.80). The statistical tests were performed between groups (Friedman), intragroup (Wilcoxon), and between the criteria considering acceptable and not acceptable restorations (McNemar), α = 0.05.

Results

A statistically significant difference was observed only for the property “superficial staining”, between groups at T2 (p = 0.01) for ER (n = 13 with score 2 or more) and SEE (n = 3 with score 2 or more) and intragroup for ER (T1, n = 1 with score 2 or more; T2, n = 13 with score 2 or more, p = 0.001) and SE (T1, n = 0 with score 2 or more; T2, n = 8 with score 2 or more p = 0.007). For the other comparisons between groups, intragroup, and between the adapted FDI and adapted USPHS criteria, there were no statistically significant differences (p ≥ 0.05).

Conclusions

It can be concluded that the different application protocols of the universal adhesive resulted in clinically “acceptable” restorations after 15.8 ± 2.7 months of follow-up. Adapted FDI and adapted USPHS criteria provided similar results to each other.

Trial registration.

Number in Brazilian Registry of Clinical Trials (ReBEC): RBR-9p3hdp. Registered 24 May 2015.
Investigating the anatomical relationship between the maxillary molars and the sinus floor in a Chinese population using cone-beam computed tomography
Authors: Zhang Xi , Li Yan , Zhang Yi , Hu Fengling , Xu Bin , Shi Xiaojun , Song Liang
Published: December 2019

Background

The anatomical relationship between the root apices of maxillary molars and the maxillary sinus floor (MSF) is important for the treatment of dental implantations and endodontic procedures. In this study, the detailed anatomical relationships between the root apices of maxillary molars and the MSF were studied in a Chinese population using CBCT.

Methods

We collected the CBCT data files of patients who visited the stomatology outpatient clinic in Shanghai Fifth People’s Hospital, Fudan University from January 1, 2017 to January 1, 2019 and measured the following items: the distance between the molar root apices and the MSF, the thickness of the mucosa and cortical bone of the MSF closest to the root apices, and the angle between the buccal and palatal roots.

Results

The shortest distances between the root apices and the MSF were 1.57 ± 3.33 mm (the mesiobuccal root of the left second molar) and 1.61 ± 3.37 mm (the mesiobuccal root of the right second molar). Apical protrusion over the inferior wall of the sinus most often occurred in the mesiobuccal root of left second molar (frequency, 20.5%). The mucosa of the MSF was thinnest at the distobuccal root of the right second molar (1.52 ± 0.85 mm), the cortical bone of the MSF was thinnest at the mesiobuccal root of the right second molar (0.46 ± 0.28 mm), and the angle between the buccal and palatal roots ranged from 12.01° to 124.2° (42.36 ± 24.33 °).

Conclusions

Among the root apices of the maxillary molars, the mesiobuccal root apex of the left second molar was closest to the MSF, and it had the highest incidence of protrusion into the sinus. The unique anatomical relationship between the maxillary molars and the MSF in this Chinese population is critical for treatment planning for dental implantation or endodontic procedures.
Predictors of contraceptive use among adolescent girls and young women (AGYW) aged 15 to 24 years in South Africa: results from the 2012 national population-based household survey
Authors: Makola L. , Mlangeni L. , Mabaso M. , Chibi B. , Sokhela Z. , Silimfe Z. , Seutlwadi L. , Naidoo D. , Khumalo S. , Mncadi A. , Zuma K.
Published: December 2019

Background

Despite a variety of contraceptives being available for women in South Africa, a considerable number of adolescent girls and young women still face challenges in using them. This paper examines socio-demographic and behavioral predictors of using contraceptives among adolescent girls and young women (AGYW) aged 15 to 24 years.

Methods

A secondary data analysis was conducted based on the 2012 population-based nationally representative multi-stage stratified cluster randomised household survey. Multivariate backward stepwise logistic regression model was used to examine socio-demographic and behavioural factors independently associated with contraceptive use amongst AGYW aged 15 to 24 years in South Africa.

Results

Out of 1460 AGYW, 78% (CI: 73.9–81.7) reported using some form of contraceptives. In the model, contraceptive use was significantly associated with secondary education [OR = 1.8 (1.2–2.7),p = 0.005], having a sexual partner within 5 years of their age [OR = 1.8 (1.2–2.5),p = 0.002], and sexual debut at age 15 years and older [OR = 2.5 (1.3–4.6),p = 0.006]. The likelihood of association decreased with other race groups-White, Coloured, and Indians/Asians [OR = 0.5 (0.3–0.7),p = 0.001], being married [OR = 0.4 (0.2–0.7),p = 0.001], never given birth [OR = 0.7 (0.5–0.9),p = 0.045], coming from rural informal [OR = 0.5 (0.3–0.9),p = 0.010] and rural formal settlements [OR = 0.5 (0.3–0.9),p = 0.020].

Conclusions

Evidence suggest that interventions should be tailor-made to meet the needs of AGYW in order to, promote use and access to contraceptives. The results also suggest that family planning interventions should target those who had not given birth in order to reduce unplanned and or unintended pregnancies and associated risk factors. These findings contribute to public health discourse and reproductive health planning for these age groups in the country.
Predictors of cervical cancer screening service utilization among commercial sex workers in Northwest Ethiopia: a case-control study
Authors: Muluneh Bekele Atinafu , Atnafu Desta Debalkie , Wassie Belaynew
Published: December 2019

Background

Although an opportunistic approach of cervical cancer screening strategy had been implemented in Ethiopia, utilization of screening services among women is still low, accounted < 1%. We hypothesize that commercial sex women in Ethiopia faced a number of obstacles in order to access screening services. Identifying the predictors influencing utilizations of the screening services is an essential effort to tailor screening program towards increasing the utilization.

Methods

An unmatched case-control study was implemented with a total sample size of 230 (46 cases and 184 controls). The study was conducted among commercial sex workers who attended confidential clinic opened for sex workers. Simple random sampling was employed. After the data were checked for completeness, consistency and accuracy, it was entered in to Epi nfo version 7 then exported to SPSS for further statistical analysis. Descriptive statistics were used to describe the profile of study participants. Logistic regression was employed to identify the predictors of cervical cancer screening uptake. P < 0.05 was computed to determine the level of statistical significance.

Results

Cervical cancer screening utilization was associated with providers’ recommendation (AOR = 6.8; 95% CI: 2.3, 9.7), history of sexually transmitted infection (AOR = 6.9; 95% CI: 1.29, 7.2), frequency of facility visit (AOR = 4.8; 95% CI: 1.97, 11.8) and history of vaginal examination (AOR = 0.21; 95% CI: 0.1, 0.68).

Conclusions

The level of cervical cancer screening service utilization was higher among women with history of STI, frequency of facility visit and providers’ recommendation. The level of cervical cancer screening service utilization was lower in women with previous vaginal examination.
Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocyte cells and in mice fed a high-fat diet
Authors: Nam Woo , Nam Seok Hyun , Kim Sung Phil , Levin Carol , Friedman Mendel
Published: December 2019

Background

The body responds to overnutrition by converting stem cells to adipocytes. In vitro and in vivo studies have shown polyphenols and other natural compounds to be anti-adipogenic, presumably due in part to their antioxidant properties. Purpurin is a highly antioxidative anthraquinone and previous studies on anthraquinones have reported numerous biological activities in cells and animals. Anthraquinones have also been used to stimulate osteoblast differentiation, an inversely-related process to that of adipocyte differentiation. We propose that due to its high antioxidative properties, purpurin administration might attenuate adipogenesis in cells and in mice.

Methods

Our study will test the effect purpurin has on adipogenesis using both in vitro and in vivo models. The in vitro model consists of tracking with various biomarkers, the differentiation of pre-adipocyte to adipocytes in cell culture. The compound will then be tested in mice fed a high-fat diet. Murine 3T3-L1 preadipocyte cells were stimulated to differentiate in the presence or absence of purpurin. The following cellular parameters were measured: intracellular reactive oxygen species (ROS), membrane potential of the mitochondria, ATP production, activation of AMPK (adenosine 5′-monophosphate-activated protein kinase), insulin-induced lipid accumulation, triglyceride accumulation, and expression of PPARγ (peroxisome proliferator activated receptor-γ) and C/EBPα (CCAAT enhancer binding protein α). In vivo, mice were fed high fat diets supplemented with various levels of purpurin. Data collected from the animals included anthropometric data, glucose tolerance test results, and postmortem plasma glucose, lipid levels, and organ examinations.

Results

The administration of purpurin at 50 and 100 μM in 3T3-L1 cells, and at 40 and 80 mg/kg in mice proved to be a sensitive range: the lower concentrations affected several measured parameters, whereas at the higher doses purpurin consistently mitigated biomarkers associated with adipogenesis, and weight gain in mice. Purpurin appears to be an effective antiadipogenic compound.

Conclusion

The anthraquinone purpurin has potent in vitro anti-adipogenic effects in cells and in vivo anti-obesity effects in mice consuming a high-fat diet. Differentiation of 3T3-L1 cells was dose-dependently inhibited by purpurin, apparently by AMPK activation. Mice on a high-fat diet experienced a dose-dependent reduction in induced weight gain of up to 55%.
The effectiveness of traditional Japanese medicine Goshajinkigan in irradiation-induced aspermatogenesis in mice
Authors: Takahashi Kumpei , Nagahori Kenta , Qu Ning , Kuramasu Miyuki , Hirayanagi Yoshie , Hayashi Shogo , Ogawa Yuki , Hatayama Naoyuki , Terayama Hayato , Suyama Kaori , Hirai Shuichi , Sakabe Kou , Itoh Masahiro
Published: December 2019

Background

Infertility and gonadal dysfunction are well known side-effects by cancer treatment in males. In particularly, chemotherapy and radiotherapy induced testicular damage, resulting in prolonged azoospermia. However, information regarding therapeutics to treat spermatogenesis disturbance after cancer treatment is scarce. Recently, we demonstrated that Goshajinkigan, a traditional Japanese medicine, can completely rescue severe busulfan-induced aspermatogenesis in mice. In this study, we aimed to detect the effects of Goshajinkigan on aspermatogenesis after irradiation.

Methods

This is animal research about the effects of traditional Japanese medicine on infertility after cancer treatment. C57BL/6 J male mice received total body irradiation (TBI: a single dose of 6Gy) at 4 weeks of age and after 60 days were reared a Goshajinkigan (TJ107)-containing or TJ107-free control diet from day 60 to day 120. Then, two untreated females were mated with a single male from each experimental group. On day 60, 120 and 150, respectively, the sets of testes and epididymis of the mice in each group after deep anesthetization were removed for histological and cytological examinations.

Results

Histological and histopathological data showed that 6Gy TBI treatment decreased the fertility rate (4/10) in the control diet group; in contrast, in the TJ107-diet group, the fertility rate was 10/10 (p < 0.05 vs. 6Gy group). Supplementation with TJ107 was found to rescue the disrupted inter-Sertoli tight junctions via the normalization of claudin11, occludin, and ZO-1 expression and reduce serum anti-germ cell autoantibodies.

Conclusions

These findings show the therapeutic effect on TBI-induced aspermatogenesis and the recovering disrupted gonadal functions by supplementation with TJ107.
Latent Dirichlet Allocation in predicting clinical trial terminations
Authors: Geletta Simon , Follett Lendie , Laugerman Marcia
Published: December 2019

Background

This study used natural language processing (NLP) and machine learning (ML) techniques to identify reliable patterns from within research narrative documents to distinguish studies that complete successfully, from the ones that terminate. Recent research findings have reported that at least 10 % of all studies that are funded by major research funding agencies terminate without yielding useful results. Since it is well-known that scientific studies that receive funding from major funding agencies are carefully planned, and rigorously vetted through the peer-review process, it was somewhat daunting to us that study-terminations are this prevalent. Moreover, our review of the literature about study terminations suggested that the reasons for study terminations are not well understood. We therefore aimed to address that knowledge gap, by seeking to identify the factors that contribute to study failures.

Method

We used data from the clinicialTrials.gov repository, from which we extracted both structured data (study characteristics), and unstructured data (the narrative description of the studies). We applied natural language processing techniques to the unstructured data to quantify the risk of termination by identifying distinctive topics that are more frequently associated with trials that are terminated and trials that are completed. We used the Latent Dirichlet Allocation (LDA) technique to derive 25 “topics” with corresponding sets of probabilities, which we then used to predict study-termination by utilizing random forest modeling. We fit two distinct models – one using only structured data as predictors and another model with both structured data and the 25 text topics derived from the unstructured data.

Results

In this paper, we demonstrate the interpretive and predictive value of LDA as it relates to predicting clinical trial failure. The results also demonstrate that the combined modeling approach yields robust predictive probabilities in terms of both sensitivity and specificity, relative to a model that utilizes the structured data alone.

Conclusions

Our study demonstrated that the use of topic modeling using LDA significantly raises the utility of unstructured data in better predicating the completion vs. termination of studies. This study sets the direction for future research to evaluate the viability of the designs of health studies.
A low-cost vision system based on the analysis of motor features for recognition and severity rating of Parkinson’s Disease
Authors: Buongiorno Domenico , Bortone Ilaria , Cascarano Giacomo Donato , Trotta Gianpaolo Francesco , Brunetti Antonio , Bevilacqua Vitoantonio
Published: December 2019

Background

Assessment and rating of Parkinson’s Disease (PD) are commonly based on the medical observation of several clinical manifestations, including the analysis of motor activities. In particular, medical specialists refer to the MDS-UPDRS (Movement Disorder Society – sponsored revision of Unified Parkinson’s Disease Rating Scale) that is the most widely used clinical scale for PD rating. However, clinical scales rely on the observation of some subtle motor phenomena that are either difficult to capture with human eyes or could be misclassified. This limitation motivated several researchers to develop intelligent systems based on machine learning algorithms able to automatically recognize the PD. Nevertheless, most of the previous studies investigated the classification between healthy subjects and PD patients without considering the automatic rating of different levels of severity.

Methods

In this context, we implemented a simple and low-cost clinical tool that can extract postural and kinematic features with the Microsoft Kinect v2 sensor in order to classify and rate PD. Thirty participants were enrolled for the purpose of the present study: sixteen PD patients rated according to MDS-UPDRS and fourteen healthy paired subjects. In order to investigate the motor abilities of the upper and lower body, we acquired and analyzed three main motor tasks: (1) gait, (2) finger tapping, and (3) foot tapping. After preliminary feature selection, different classifiers based on Support Vector Machine (SVM) and Artificial Neural Networks (ANN) were trained and evaluated for the best solution.

Results

Concerning the gait analysis, results showed that the ANN classifier performed the best by reaching 89.4% of accuracy with only nine features in diagnosis PD and 95.0% of accuracy with only six features in rating PD severity. Regarding the finger and foot tapping analysis, results showed that an SVM using the extracted features was able to classify healthy subjects versus PD patients with great performances by reaching 87.1% of accuracy. The results of the classification between mild and moderate PD patients indicated that the foot tapping features were the most representative ones to discriminate (81.0% of accuracy).

Conclusions

The results of this study have shown how a low-cost vision-based system can automatically detect subtle phenomena featuring the PD. Our findings suggest that the proposed tool can support medical specialists in the assessment and rating of PD patients in a real clinical scenario.
Working with patients and the public to design an electronic health record interface: a qualitative mixed-methods study
Authors: Warren Leigh R. , Harrison Matthew , Arora Sonal , Darzi Ara
Published: December 2019

Background

Enabling patients to be active users of their own medical records may promote the delivery of safe, efficient care across settings. Patients are rarely involved in designing digital health record systems which may make them unsuitable for patient use. We aimed to develop an evidence-based electronic health record (EHR) interface and participatory design process by involving patients and the public.

Methods

Participants were recruited to multi-step workshops involving individual and group design activities. A mixture of quantitative and qualitative questionnaires and observational methods were used to collect participant perspectives on interface design and feedback on the workshop design process.

Results

48 recruited participants identified several design principles and components of a patient-centred electronic medical record interface. Most participants indicated that an interactive timeline would be an appropriate way to depict a medical history. Several key principles and design components, including the use of specific colours and shapes for clinical events, were identified. Participants found the workshop design process utilised to be useful, interesting, enjoyable and beneficial to their understanding of the challenges of information exchange in healthcare.

Conclusion

Patients and the public should be involved in EHR interface design if these systems are to be suitable for use by patient-users. Workshops, as used in this study, can provide an engaging format for patient design input. Design principles and components highlighted in this study should be considered when patient-facing EHR design interfaces are being developed.
Correction to: Responding to policy makers’ evaluation needs: combining experimental and quasi-experimental approaches to estimate the impact of performance based financing in Burkina Faso
Authors: De Allegri Manuela , Lohmann Julia , Souares Aurélia , Hillebrecht Michael , Hamadou Saidou , Hien Hervé , Haidara Ousmane , Robyn Paul Jacob
Published: December 2019

Due to an error introduced during copyediting of this article [1], there are two corrections about the Figs. 1. The caption of Fig. 1 should be changed to “Study design”. 2. The Fig. 2 is missing.
Adaptation, modification, and psychometric assessment of a Norwegian version of the Basel extent of rationing of nursing care for nursing homes instrument (BERNCA-NH)
Authors: Norman Rebecka Maria , Sjetne Ingeborg Strømseng
Published: December 2019

Background

To our knowledge, no instrument has been developed and tested for measuring unfinished care in Norwegian nursing home settings. The Basel Extent of Rationing of Nursing Care for Nursing Homes instrument (BERNCA-NH) was developed and validated in Switzerland to measure the extent of implicit rationing of nursing care in nursing homes. The BERNCA-NH comprises a list of nursing care activities in which a care worker reports the frequency to which activities were left unfinished over the last 7 working days as a result of lack of time. The aim of this study was to adapt and modify a Norwegian version of the BERNCA-NH intended for all care workers, and assess the instruments’ psychometric properties in a Norwegian nursing home setting.

Methods

The BERNCA-NH was translated into Norwegian and modified to fit the Norwegian setting with inputs from individual cognitive interviews with informants from the target population. The instrument was then tested in a web-based survey with a final sample of 931 care workers in 162 nursing home units in different parts of Norway. The psychometric evaluation included score distribution, response completeness and confirmatory factor analysis (CFA) of a hypothesised factor structure and evaluation of internal consistency. Hypothesised relation to other variables was assessed through correlations between the subscale scores and three global ratings.

Results

The Norwegian version of BERNCA-NH comprised four subscales labelled: routine care, ‘when required’ care, documentation and psychosocial care. All subscales demonstrated good internal consistency. The CFA supported the four-factor structure with fit statistics indicating a robust model. There were moderate to strong bivariate associations between the BERNCA-NH subscales and the three global ratings. Three items which were not relevant for all care workers were not included in the subscales and treated as single items.

Conclusions

This study found good psychometric properties of the Norwegian version BERNCA-NH, assessed in a sample of care workers in Norwegian nursing homes. The results indicate that the instrument can be used to measure unfinished care in similar settings.
Protocol of a longitudinal study on the specific needs of Syrian refugee families in Switzerland
Authors: El Ghaziri Nahema , Blaser Jérémie , Darwiche Joëlle , Suris Joan-Carles , Sanchis Zozaya Javier , Marion-Veyron Régis , Spini Dario , Bodenmann Patrick
Published: December 2019

Background

The ongoing Syrian civil war has led to massive population displacements, leading to the reorganization of the asylum policies of several countries. Accordingly, like other European countries, the Swiss government has recently chosen to implement a specific resettlement program. This program is characterized by the fact that the whole nuclear family is granted a work and residence permit upon arrival, and benefits from enhanced integration services. The aim of the present project is to evaluate the effects of the Swiss resettlement program, with a special focus on mental health, while adopting a family perspective.

Methods

The outcomes of 15 Syrian families taking part in this program will be compared to those of 15 Syrian families that came to Switzerland through other means (i.e., following the usual asylum procedure, which is much more stressful and time consuming). Each family member above 8 years old will be invited to participate to a 3-wave longitudinal survey concerning the resettlement process: upon arrival in the collective shelters, six and 12 months later. Questionnaires will be used for the evaluation of participants’ mental health, risk behaviors, general health, romantic relationship, parent-child relationship, family functioning, parentification, social support, and social identities related to group belongingness.

Discussion

The findings of the present project will provide longitudinal information on Syrian refugees. A comprehensive approach will be adopted by screening potential difficulties that the sample may be faced with and potential strengths that participants may rely on. Accordingly, physical and mental health, as well as the quality of family functioning, the feeling of support and of belongingness to different groups will be evaluated.

We will also compare the results of families who had the chance to immigrate through the Swiss resettlement program, to the results of families that did not. This comparison will allow the elaboration of hypotheses regarding adjusted asylum policies. Furthermore, it will enhance our knowledge regarding the impact of displacement on the family system. Indeed, although the role of the family for the well-being of adults and children has been established, surprisingly few studies have adopted this focus in the asylum field.
Crossing fitness valleys via double substitutions within codons
Authors: Belinky Frida , Sela Itamar , Rogozin Igor B. , Koonin Eugene V.
Published: December 2019

Background

Single nucleotide substitutions in protein-coding genes can be divided into synonymous (S), with little fitness effect, and non-synonymous (N) ones that alter amino acids and thus generally have a greater effect. Most of the N substitutions are affected by purifying selection that eliminates them from evolving populations. However, additional mutations of nearby bases potentially could alleviate the deleterious effect of single substitutions, making them subject to positive selection. To elucidate the effects of selection on double substitutions in all codons, it is critical to differentiate selection from mutational biases.

Results

We addressed the evolutionary regimes of within-codon double substitutions in 37 groups of closely related prokaryotic genomes from diverse phyla by comparing the fractions of double substitutions within codons to those of the equivalent double S substitutions in adjacent codons. Under the assumption that substitutions occur one at a time, all within-codon double substitutions can be represented as “ancestral-intermediate-final” sequences (where “intermediate” refers to the first single substitution and “final” refers to the second substitution) and can be partitioned into four classes: (1) SS, S intermediate–S final; (2) SN, S intermediate–N final; (3) NS, N intermediate–S final; and (4) NN, N intermediate–N final. We found that the selective pressure on the second substitution markedly differs among these classes of double substitutions. Analogous to single S (synonymous) substitutions, SS double substitutions evolve neutrally, whereas analogous to single N (non-synonymous) substitutions, SN double substitutions are subject to purifying selection. In contrast, NS show positive selection on the second step because the original amino acid is recovered. The NN double substitutions are heterogeneous and can be subject to either purifying or positive selection, or evolve neutrally, depending on the amino acid similarity between the final or intermediate and the ancestral states.

Conclusions

The results of the present, comprehensive analysis of the evolutionary landscape of within-codon double substitutions reaffirm the largely conservative regime of protein evolution. However, the second step of a double substitution can be subject to positive selection when the first step is deleterious. Such positive selection can result in frequent crossing of valleys on the fitness landscape.
Calibration: the Achilles heel of predictive analytics
Authors:   On behalf of Topic Group ‘Evaluating diagnostic tests and prediction models’ of the STRATOS initiative, Van Calster Ben , McLernon David J. , van Smeden Maarten , Wynants Laure , Steyerberg Ewout W.
Published: December 2019

Background

The assessment of calibration performance of risk prediction models based on regression or more flexible machine learning algorithms receives little attention.

Main text

Herein, we argue that this needs to change immediately because poorly calibrated algorithms can be misleading and potentially harmful for clinical decision-making. We summarize how to avoid poor calibration at algorithm development and how to assess calibration at algorithm validation, emphasizing balance between model complexity and the available sample size. At external validation, calibration curves require sufficiently large samples. Algorithm updating should be considered for appropriate support of clinical practice.

Conclusion

Efforts are required to avoid poor calibration when developing prediction models, to evaluate calibration when validating models, and to update models when indicated. The ultimate aim is to optimize the utility of predictive analytics for shared decision-making and patient counseling.
RNA disruption indicates CHOP therapy efficacy in canine lymphoma
Authors: Parissenti Amadeo M. , Pritzker Laura B. , Guo Baoqing , Narendrula Rashmi , Wang Shirly Xiaohui , Lin Lin Laura , Pei Jingchun , Skowronski Karolina , Bienzle Dorothee , Woods J. Paul , Pritzker Kenneth P. H. , Coomber Brenda L.
Published: December 2019

Background

Assessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter. However, no consistent correlation has been made with prognostic indicators and the length or absence of clinical remission based on lymph node size. RNA disruption measured mid-therapy has been correlated with increased disease-free survival in recent studies of human cancer and was assessed in this study of canine lymphoma patients. Fine needle aspirate samples were taken before treatment and at weeks 3, 6, and 11 of CHOP therapy. RNA was isolated from these samples and assessed using an Agilent Bioanalyzer. RNA disruption assay (RDA) analysis was performed on the data from the resulting electropherograms.

Results

An increased RNA disruption index (RDI) score was significantly associated with improved progression-free survival.

Conclusions

Predicting the risk of early relapse during chemotherapy could benefit veterinary patients by reducing ineffective treatment and could allow veterinary oncologists to switch earlier to a more effective drug regimen.
Low BRAF V600 mutation prevalence in primary skin nodular melanoma in Indonesia: a real-time PCR detection among Javanese patients
Authors: Rinonce Hanggoro Tri , Aji Rovi Panji Mustiko , Hayati Ni’mah , Pudjohartono Maria Fransiska , Kameswari Bidari , Irianiwati
Published: December 2019

Background

Cutaneous melanoma is a rare, aggressive skin malignancy with a high mortality rate. Although only contributing 7.6% of the cases worldwide, Asia is responsible for 18.6% of deaths from cutaneous melanoma. BRAF V600 mutation presents a potential prognostic predictor in melanoma. Unfortunately, studies on that mutation in melanoma, particularly nodular subtype, in Indonesia are still scarce. This research aimed to investigate the prevalence of BRAF V600 mutation in primary skin nodular melanoma in Yogyakarta and Central Java, Indonesia. Its association with clinicopathological parameters was also analyzed.

Methods

Forty paraffin-embedded tissue samples from primary skin nodular melanoma cases in 2011–2018 were collected from the two biggest referral hospitals in Yogyakarta and Central Java, Indonesia. The BRAF V600 mutation status was assessed using qualitative real-time PCR and its associations with age, sex, anatomic location, lymph node metastasis, tumor thickness, ulceration, mitotic index, necrosis, lymphovascular invasion, and tumor-infiltrating lymphocytes were analyzed.

Results

BRAF V600 mutations were found in 4 (10%) samples. These mutations were significantly associated with the central (non-extremity) region (p = 0.013) and presence of lymphovascular invasion (p = 0.005). However, it was not associated with any other variables analyzed in this study.

Conclusion

The prevalence of BRAF V600 mutation in Indonesian primary skin nodular melanoma cases is low and significantly associated with anatomic location and lymphovascular invasion. It is lower than prevalences in other Asian populations as well as in Caucasian populations and suggests that melanoma cases in Javanese people may have distinct clinicopathological characteristics from other Asian ethnicities.
The effect of 5α-oleandrin on keloid fibroblast activities
Authors: Dachlan Ishandono , Wirohadidjojo Yohanes Widodo , Wahyuningsih Mae Sri Hartati , Aryandono Teguh , Soebono Hardyanto , Afandy Dwiki
Published: December 2019

Background

Keloids develop due to hyperactivity of keloid fibroblast (KF) in proliferation, migration, and collagen deposition along with low rates of collagen degradation. These are a result of the Wnt/β catenin signaling pathways under stimulation of TGF-β. 5α-oleandrin can suppress Wnt-targeted genes of osteosarcoma cells. We aimed to evaluate the anti-fibrotic effects of 5α-oleandrin on KF activities.

Methods

We collected the core of keloid materials from six patients who underwent keloid debulking surgery. Passage 4 of KF cells were then treated with mitomycin-C, 5α-oleandrin, and dilution medium as the negative control. To determine the effective dose of 5α-oleandrin, we diluted 5α-oleandrin into various concentrations. The incubation periods were 24 h, 48 h, and 72 h. The anti-proliferation and anti-fibrotic properties were measured using standard assay.

Results

Both the mitomycin-C and 5α-oleandrin treated groups indicated decrease in proliferation index (86.16 ± 4.20% and 73.76 ± 4.94%, respectively), collagen deposition index (90.26 ± 1.72% and 71.35 ± 4.26%, respectively), and migration capacity (33.51 ± 1.50% and 28.57 ± 1.58%, respectively). These were significant changes (p ≤ 0.05) compared to the non-treated group. Antifibrotic activities of 5α-oleandrin in cellular proliferation and collagen deposition were better than mitomycin-C.

Conclusions

The 5α-oleandrin has good antifibrotic effect in keloid fibroblast activities.
Use of air stacking to improve pulmonary function in Indonesian Duchenne muscular dystrophy patients: bridging the standard of care gap in low middle income country setting
Authors: Iskandar Kristy , Sunartini  , Nugrahanto Andika Priamas , Ilma Nissya , Kalim Alvin Santoso , Adistyawan Guritno , Siswanto  , Naning Roni
Published: December 2019

Background

Duchenne Muscular Dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease, characterized by progressive loss of muscle strength. Respiratory failure is the main cause of morbidity and mortality in DMD patients. Respiratory devices have been reported to increase the effectiveness of cough and pulmonary function, thus prolong the survival rate. However, there is scarcity of studies about DMD patients’ respiratory profiles and usage of respiratory devices in Indonesia.

Methods

We recruited 8 Indonesian DMD patients in Dr. Sardjito Hospital and UGM Academic Hospital, Yogyakarta. Baseline pulmonary function was measured using spirometry. Peak Cough Flow was measured at baseline, with chest compression, after air stacking with manual ventilation bag, and with the combined techniques. Data recorded was presented as mean ± SD and analysed using ANOVA.

Results

Here we show the respiratory profiles from 8 non-ambulatory DMD patients (mean age: 13.25 ± 3.96 years old) confirmed by genetic testing. None of them had access to respiratory devices. Spirometry measurements showed 7 of 8 patients had severe restrictive pulmonary function with mean FEV1/FVC 22.40 ± 10.30% of predictive values (normal ratio > 70%). In addition, all patients showed poor cough performances measured by peak cough flowmeter (160 ± 44.58 L/min (normal value > 270 L/min)) that were improved by air stacking using a manual ventilation bag (167.4 ± 46.72 L/min). Three patients who had nocturnal hypoventilation did not have daytime hypercapnia. Manual ventilation bag or mechanical in−/ex-sufflation was indicated in 75% of patients while nocturnal assisted ventilation was indicated in 50% of patients. Neither daytime assisted ventilation nor tracheostomy was indicated in these patients.

Conclusion

Use of manual exsufflation in combination with the manual ventilation bag for air stacking to improve cough performance is recommended as the first step of respiratory management in DMD patients. Provision of manual ventilation bag serve as an affordable and effective device for respiratory support in the early stage of respiratory involvement in those non-ambulatory patients with DMD.
Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
Authors: Arfian Nur , Setyaningsih Wiwit Ananda Wahyu , Romi Muhammad Mansyur , Sari Dwi Cahyani Ratna
Published: December 2019

Background

Diabetes Mellitus (DM) is one of the metabolic diseases which leads to fatty tissue injury, and consequently inducing lipotoxicity and cellular senescence. This condition contributes to endothelial dysfunction with chronic inflammation and organ damage. Heparanase which has a role in disrupting endothelial surface layer (glycocalyx) may promote endothelial Nitric oxide synthase (eNOS) reduction and inflammation. However, its relationship with DM and organ injury has not been fully elucidated yet. This study aimed to determine how heparanase from fatty tissue may contribute to endothelial dysfunction and inflammation in patients with hyperglycemia and in a hyperglycemia model in rats.

Methods

This population study with a cross-sectional design was conducted with 28 subjects without diagnosis and medication of DM. Fasting blood glucose levels, lipid profile, heparanase protein, MCP-1 protein and HbA1c were quantified. In vivo study was performed with a diabetic model in Wistar rats induced with streptozotocin 60 mg/kg body weight by single intraperitoneal injection. Rats were euthanized after 1 month (DM1 group, n = 6), 2 months (DM2 group, n = 6) and 4 months (DM4 group, n = 6). White Adipose Tissue (WAT) was harvested from visceral fat. Real Time and Reverse Transcriptase-PCR (RT-PCR) was done to quantify expressions of heparanase, MCP-1, eNOS, IL-6 and p-16 (senescence). Immunostaining was performed to localize MCP-1 and macrophage (CD68). Western blot tests were used to examine eNOS, MCP-1 and heparanase protein expression.

Results

This study revealed associations between blood glucose levels with higher HbA1c, LDL, cholesterol, heparanase and MCP-1. The in vivo study also revealed lipid levels as the source of Heparanase and MCP-1 mRNA and protein expressions. This finding was associated with inflammation, cellular senescence and macrophage infiltration in fat tissue based on immunostaining and qRT-PCR analysis. RT-PCR revealed significantly lower expression of eNOS and higher expression of IL-6 in DM groups compared to the control group.

Conclusion

Heparanase upregulation in fat tissue was associated with endothelial injury and inflammation in hyperglycemia conditions.
Genepanel.iobio - an easy to use web tool for generating disease- and phenotype-associated gene lists
Authors: Ekawade Aditya , Velinder Matt , Ward Alistair , DiSera Tonya , Miller Chase , Qiao Yi , Marth Gabor
Published: December 2019

When ordering genetic testing or triaging candidate variants in exome and genome sequencing studies, it is critical to generate and test a comprehensive list of candidate genes that succinctly describe the complete and objective phenotypic features of disease. Significant efforts have been made to curate gene:disease associations both in academic research and commercial genetic testing laboratory settings. However, many of these valuable resources exist as islands and must be used independently, generating static, single-resource gene:disease association lists. Here we describe genepanel.iobio (https://genepanel.iobio.io) an easy to use, free and open-source web tool for generating disease- and phenotype-associated gene lists from multiple gene:disease association resources, including the NCBI Genetic Testing Registry (GTR), Phenolyzer, and the Human Phenotype Ontology (HPO). We demonstrate the utility of genepanel.iobio by applying it to complex, rare and undiagnosed disease cases that had reached a diagnostic conclusion. We find that genepanel.iobio is able to correctly prioritize the gene containing the diagnostic variant in roughly half of these challenging cases. Importantly, each component resource contributed diagnostic value, showing the benefits of this aggregate approach. We expect genepanel.iobio will improve the ease and diagnostic value of generating gene:disease association lists for genetic test ordering and whole genome or exome sequencing variant prioritization.
Competitive endogenous RNA (ceRNA) regulation network of lncRNAs, miRNAs, and mRNAs in Wilms tumour
Authors: Tang Fucai , Lu Zechao , Wang Jiamin , Li Zhibiao , Wu Weijia , Duan Haifeng , He Zhaohui
Published: December 2019

Background

Competitive endogenous RNAs (ceRNAs) have revealed a new mechanism of interaction between RNAs. However, an understanding of the ceRNA regulatory network in Wilms tumour (WT) remains limited.

Methods

The expression profiles of mRNAs, miRNAs and lncRNAs in Wilms tumour samples and normal samples were obtained from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database. The EdgeR package was employed to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analyses via the ClusterProfile R package were performed, and the lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape. Subsequently, the correlation between the ceRNA network and overall survival was analysed.

Results

A total of 2037 lncRNAs, 154 miRNAs and 3609 mRNAs were identified as differentially expressed RNAs in Wilms tumour. Of those, 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in the ceRNA regulatory network. The results of Gene Ontology (GO) analysis revealed that the differentially expressed genes (DEGs) were mainly enriched in terms related to response to mechanical stimuli, transcription factor complexes, and transcription factor activity (related to RNA polymerase II proximal promoter sequence-specific DNA binding). The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the DEGs were mainly enriched in pathways related to the cell cycle. The survival analysis results showed that 16 out of the 205 lncRNAs, 1 out of 26 miRNAs and 5 out of 143 mRNAs were associated with overall survival in Wilms tumour patients (P < 0.05).

Conclusions

CeRNA networks play an important role in Wilms tumour. This finding might provide effective, novel insights for further understanding the mechanisms underlying Wilms tumour.