bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case report of familial 4q13.3 microdeletion in three individuals with syndromic intellectual disability
Authors: Maldžienė Živilė , Vaitėnienė Evelina M. , Aleksiūnienė Beata , Utkus Algirdas , Preikšaitienė Eglė 
Published: April 2020

Abstract
Background
Interstitial 4q deletions are rare chromosomal alterations. Most of the previously reported deletions involving the 4q13.3 region are large chromosomal alterations with a common loss of band 4q21 resulting in marked growth restriction, severe intellectual disability, and absent or severely delayed speech. A microdeletion of 4q13.3 hasn’t been previously reported. We discuss the involvement of genes and the observed phenotype, comparing it with that of previously reported patients.

Case presentation
We report on a 4q13.3 microdeletion detected in three affected individuals of a Lithuanian family. The clinical features of two affected children and their affected mother are very similar and include short stature, congenital heart defect, skeletal anomalies, minor facial anomalies, delayed puberty, and intellectual disability. Whole genome SNP microarray analysis of one child revealed an interstitial 4q13.3 microdeletion, 1.56 Mb in size. FISH analysis confirmed the deletion in the proband and identified the same deletion in her affected sib and mother, while it was not detected in a healthy sib. Deletion includes ADAMTS3, ANKRD17, COX18, GC, and NPFFR2 protein-coding genes.

Conclusions
Our findings suggest that 4q13.3 microdeletion is a cause of a recognizable phenotype of three affected individuals. The detected microdeletion is the smallest interstitial deletion in 4q13. We highlight ADAMTS3, ANKRD17 and RNU4ATAC9P as candidate genes for intellectual disability, growth retardation and congenital heart defect.
Repeated fed-batch strategy and metabolomic analysis to achieve high docosahexaenoic acid productivity in Crypthecodinium cohnii
Authors: Liu Liangsen , Wang Fangzhong , Pei Guangsheng , Cui Jinyu , Diao Jinjin , Lv Mingming , Chen Lei , Zhang Weiwen 
Published: April 2020

Abstract
Background
Docosahexaenoic acid (DHA) is essential for human diet. However, high production cost of DHA using C. cohnii makes it currently less competitive commercially, which is mainly caused by low DHA productivity. In recent years, repeated fed-batch strategies have been evaluated for increasing the production of many fermentation products. The reduction in terms of stability of culture system was one of the major challenges for repeated fed-batch fermentation. However, the possible mechanisms responsible for the decreased stability of the culture system in the repeated fed-batch fermentation are so far less investigated, restricting the efforts to further improve the productivity. In this study, a repeated fed-batch strategy for DHA production using C. cohnii M-1-2 was evaluated to improve DHA productivity and reduce production cost, and then the underlying mechanisms related to the gradually decreased stability of the culture system in repeated fed-batch culture were explored through LC– and GC–MS metabolomic analyses.

Results
It was discovered that glucose concentration at 15–27 g/L and 80% medium replacement ratio were suitable for the growth of C. cohnii M-1-2 during the repeated fed-batch culture. A four-cycle repeated fed-batch culture was successfully developed and assessed at the optimum cultivation parameters, resulting in increasing the total DHA productivity by 26.28% compared with the highest DHA productivity of 57.08 mg/L/h reported using C. cohnii, including the time required for preparing seed culture and fermentor. In addition, LC– and GC–MS metabolomics analyses showed that the gradually decreased nitrogen utilization capacity, and down-regulated glycolysis and TCA cycle were correlated with the decreased stability of the culture system during the long-time repeated fed-batch culture. At last, some biomarkers, such as Pyr, Cit, OXA, FUM, l-tryptophan, l-threonine, l-leucine, serotonin, and 4-guanidinobutyric acid, correlated with the stability of culture system of C. cohnii M-1-2 were identified.

Conclusions
The study proved that repeated fed-batch cultivation was an efficient and energy-saving strategy for industrial production of DHA using C. cohnii, which could also be useful for cultivation of other microbes to improve productivity and reduce production cost. In addition, the mechanisms study at metabolite level can also be useful to further optimize production processes for C. cohnii and other microbes.
Insight into the role of p62 in the cisplatin resistant mechanisms of ovarian cancer
Authors: Yan Xiao-Yu , Qu Xian-Zhi , Xu Long , Yu Si-Hang , Tian Rui , Zhong Xin-Ru , Sun Lian-Kun , Su Jing 
Published: April 2020

AbstractCisplatin is a platinum-based first-line drug for treating ovarian cancer. However, chemotherapy tolerance has limited the efficacy of cisplatin for ovarian cancer patients. Research has demonstrated that cisplatin causes changes in cell survival and death signaling pathways through its interaction with macromolecules and organelles, which indicates that investigation into the DNA off-target effects of cisplatin may provide critical insights into the mechanisms underlying drug resistance. The multifunctional protein p62 works as a signaling hub in the regulation of pro-survival transcriptional factors NF-κB and Nrf2 and connects autophagy and apoptotic signals, which play important roles in maintaining cell homeostasis. In this review, we discuss the role of p62 in cisplatin resistance by exploring p62-associated signaling pathways based on current studies and our work. Insights into these resistance mechanisms may lead to more effective therapeutic strategies for ovarian cancer by targeting p62.
Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling
Authors: Al-Obeed Omar , El-Obeid Adila Salih , Matou-Nasri Sabine , Vaali-Mohammed Mansoor-Ali , AlHaidan Yazeid , Elwatidy Mohammed , Al Dosary Hamad , Alehaideb Zeyad , Alkhayal Khayal , Haseeb Adil , McKerrow James , Ahmad Rehan , Abdulla Maha-Hamadien 
Published: April 2020

Abstract
Background
Colorectal carcinoma is one of the most deadly cancers that requests effective and safe chemotherapy. Evaluation of natural product-based anticancer drugs as adjuvant treatment with fewer side effects is largely unexplored research fields. Herbal melanin (HM) is an extract of the seed coats of Nigella sativa that modulates an inflammatory response through toll-like receptor 4 (TLR4). This TLR4 receptor is also involved in the modulation of apoptosis. We therefore explored the anticancer potential of HM and specifically its effect on the molecular mechanisms underlying adenocarcinoma and metastatic colorectal cancer (mCRC) cell death in vitro.

Methods
Cell viability was evaluated using the MTT assay. Cellular reactive oxygen species (ROS), glutathione levels, and apoptotic status were assessed using fluorometric and colorimetric detection methods. HM-induced apoptotic and other signaling pathways were investigated using Western blot technology and mitochondrial transition pore assay kit. TLR4 receptor downregulation and blockade were performed using siRNA technology and neutralizing antibody, respectively.

Results
Our results showed that HM inhibited the proliferation of the colorectal adenocarcinoma HT29 and mCRC SW620 cell lines. Furthermore, HM enhanced ROS production and decreased glutathione levels. HM-induced apoptosis was associated with mitochondrial outer membrane permeability and cytochrome c release, inhibition of the Bcl2 family proteins, and activation of caspase-3/-7. In addition, HM modulated MAPK pathways by activating the JNK pathway and by inhibiting ERK phosphorylation. TLR4 receptor downregulation enhanced HM-induced apoptosis while TLR4 receptor blockade partially alleviated HM-inhibited ERK phosphorylation.

Conclusion
Altogether, these findings indicate that HM exerts pro-apoptotic effects and inhibits MAPK pathway through TLR4 in mCRC and colorectal adenocarcinoma cells, suggesting HM as a promising natural-based drug for the treatment of colorectal cancer.
Effects of natural polyphenol-rich pomegranate juice supplementation on plasma ion and lipid profiles following resistance exercise: a placebo-controlled trial
Authors: Ammar Achraf , Trabelsi Khaled , Bailey Stephen J. , Turki Mouna , Bragazzi Nicola Luigi , Boukhris Omar , El Abed Kais , Bouaziz Mohamed , Ayadi Fatma , Driss Tarak , Souissi Nizar , Chtourou Hamdi , Hökelmann Anita 
Published: April 2020

Abstract
Background
Pomegranate juice (POMj) contains abundant soluble polyphenolic antioxidant compounds and is recommended for its cardioprotective/atheroprotective properties. However, very few studies have investigated the efficacy of POMj supplementation to alter physiological responses during intensive physical exercise. This placebo-controlled study aimed to examine whether supplementation with natural polyphenol-rich-POMj could influence the ionic or lipid responses to an intensive resistance training session in elite athletes.

Methods
Nine elite weightlifters (21 ± 1 years) performed two Olympic-weightlifting sessions after ingesting placebo and POMj supplements. Venous blood samples were collected at rest and 3 min after each session for assessment of plasma sodium ([Na+]), potassium ([K+]), chloride ([Cl−]), calcium ([Ca2+]), triglyceride ([TG]) and high-density lipoprotein ([HDL-C]), low-density lipoprotein ([HDL-C]) and total ([TC]) cholesterol concentrations.

Results
Plasma [K+] and [TG] were lowered post-exercise compared to resting values in the PLA condition (p = 0.03 for K+ and p = 0.02 for TG) with no pre-to-post exercise differences in the other plasma ion and lipid markers (p > 0.05). Compared to rest, plasma [Na+] and [Cl−] were increased (p = 0.04, %change = 4.10% for Na+ and p = 0.02, %change = 4.44% for Cl−), but there were no differences in the other plasma ion or lipid markers post-exercise after POMj supplementation (p > 0.05). Post-exercise plasma [Na+], [Cl−], and [HDL-C] were greater following POMj supplementation compared to PLA (p = 0.01 for Cl- and HDL-C, p = 0.02 for Na+, and p = 0.04 for TC), with no between-supplement post-exercise differences in the other ion and lipid markers (p > 0.05).

Conclusion
In conclusion, supplementation with POMj has the potential to attenuate the acute imbalance of plasma [K+] and to improve blood lipid responses (i.e., HDL-C) following resistance exercises in elite weightlifters. However, further large research in both athletic and non-athletic populations is needed to corroborate these preliminary observations and to elucidate the potential underlying mechanisms and translational potential of our novel observations.

Trial registration
Name of the registry:ClinicalTrials.gov PRS
The registration number:NCT02697903.
Date of Registry: 03/03/2016 ‘Retrospectively registered’.
The registration title: Pomegranate Improve Biological Recovery Kinetics in Elite Weightlifter.

Graphical abstract
Recent developments and emerging trends of mass spectrometric methods in plant hormone analysis: a review
Authors: Wang Liyuan , Zou Yilin , Kaw Han Yeong , Wang Gang , Sun Huaze , Cai Long , Li Chengyu , Meng Long-Yue , Li Donghao 
Published: April 2020

AbstractPlant hormones are naturally occurring small molecule compounds which are present at trace amounts in plant. They play a pivotal role in the regulation of plant growth. The biological activity of plant hormones depends on their concentrations in the plant, thus, accurate determination of plant hormone is paramount. However, the complex plant matrix, wide polarity range and low concentration of plant hormones are the main hindrances to effective analyses of plant hormone even when state-of-the-art analytical techniques are employed. These factors substantially influence the accuracy of analytical results. So far, significant progress has been realized in the analysis of plant hormones, particularly in sample pretreatment techniques and mass spectrometric methods. This review describes the classic extraction and modern microextraction techniques used to analyze plant hormone. Advancements in solid phase microextraction (SPME) methods have been driven by the ever-increasing requirement for dynamic and in vivo identification of the spatial distribution of plant hormones in real-life plant samples, which would contribute greatly to the burgeoning field of plant hormone investigation. In this review, we describe advances in various aspects of mass spectrometry methods. Many fragmentation patterns are analyzed to provide the theoretical basis for the establishment of a mass spectral database for the analysis of plant hormones. We hope to provide a technical guide for further discovery of new plant hormones. More than 140 research studies on plant hormone published in the past decade are reviewed, with a particular emphasis on the recent advances in mass spectrometry and sample pretreatment techniques in the analysis of plant hormone. The potential progress for further research in plant hormones analysis is also highlighted.
Development of a universal endogenous qPCR control for eukaryotic DNA samples
Authors: Mittelberger Cecilia , Obkircher Lisa , Oberkofler Vicky , Ianeselli Alan , Kerschbamer Christine , Gallmetzer Andreas , Reyes-Dominguez Yazmid , Letschka Thomas , Janik Katrin 
Published: April 2020

Abstract
Background
Phytoplasma are obligate intracellular plant-pathogenic bacteria that infect a broad range of plant species and are transmitted by different insect species. Quantitative real-time PCR (qPCR) is one of the most commonly used techniques for pathogen detection, especially for pathogens that cannot be cultivated outside their host like phytoplasma. PCR analysis requires the purification of total DNA from the sample and subsequent amplification of pathogen DNA with specific primers. The purified DNA contains mainly host DNA and only a marginal proportion is of phytoplasmal origin. Therefore, detection of phytoplasma DNA in a host DNA background must be sensitive, specific and reliable and is highly dependent on the quality and concentration of the purified DNA. DNA quality and concentration and the presence of PCR-inhibitors therefore have a direct impact on pathogen detection. Thus, it is indispensable for PCR-based diagnostic tests to validate the DNA preparation and DNA integrity before interpreting diagnostic results, especially in case that no pathogen DNA is detected. The use of an internal control allows to evaluate DNA integrity and the detection of PCR-inhibiting substances. Internal controls are generally host-specific or limited to a defined group of related species. A control suitable for the broad range of phytoplasma hosts comprising different insect and plant species is still missing.

Results
We developed a primer and probe combination that allows amplification of a conserved stretch of the eukaryotic 28S rDNA gene. The developed endogenous qPCR control serves as a DNA quality control and allows the analysis of different eukaryotic host species, including plants, insects, fish, fungi, mammals and human with a single primer/probe set in single- or multiplex assays.

Conclusions
Quality and performance control is indispensable for pathogen detection by qPCR. Several plant pathogens are transmitted by insects and have a broad range of host species. The newly developed endogenous control can be used with all so far tested eukaryotic species and since multiplexing is possible, the described primer and probe set can be easily combined with other PCR-based pathogen detection systems.
Functional movement compensations persist in individuals with hip osteoarthritis performing the five times sit-to-stand test 1 year after total hip arthroplasty
Authors: Esbjörnsson Anna-Clara , Naili Josefine E. 
Published: April 2020

Abstract
Background
Methods to quantify and evaluate function are important for development of specific rehabilitation interventions. This study aimed to evaluate functional movement compensation in individuals with hip osteoarthritis performing the five times sit-to-stand test and change following total hip arthroplasty. To this end, trajectories of the body’s center of mass in the medial-lateral and anterior-posterior dimensions were quantified prior to and 1 year after total hip arthroplasty and compared to a healthy control group.

Methods
Twenty-eight individuals with hip osteoarthritis and 21 matched healthy controls were enrolled in this prospective study. Within 1 month prior to and 1 year after total hip arthroplasty, performance on the five times sit-to-stand test was evaluated using three-dimensional motion analysis and perceived pain using a visual analog scale. The center of mass trajectories for the medial-lateral and the anterior-posterior dimensions were identified, and the area under the curve was calculated, respectively. Repeated measures ANOVA were used to evaluate differences in the area under the curve, between pre- and postoperative performance, and between participants with hip osteoarthritis and controls.

Results
Preoperatively, individuals with hip osteoarthritis displayed a larger contralateral shift (p < 0.001) and forward displacement of the center of mass (p = 0.022) compared to controls. After surgery, deviations in both dimensions were reduced (medial-lateral p = 0.013; anterior-posterior p = 0.009). However, as compared to controls, the contralateral shift of the center of mass remained larger (p = 0.010), indicative of persistent asymmetric limb loading. Perceived pain was significantly reduced postoperatively (p < 0.001).

Conclusions
By quantifying the center of mass trajectory during five times sit-to-stand test performance, functional movement compensations could be detected and evaluated over time. Prior to total hip arthroplasty, individuals with hip osteoarthritis presented with an increased contralateral shift and forward displacement of the center of mass, representing a strategy to reduce pain by unloading the affected hip and reducing required hip and knee extension moments. After surgery, individuals with total hip arthroplasty displayed a persistent increased contralateral shift as compared to controls. This finding has implications for rehabilitation, where more focus must be directed towards normalizing loading of the limbs.
Diagnosis support systems for rare diseases: a scoping review
Authors: Faviez Carole , Chen Xiaoyi , Garcelon Nicolas , Neuraz Antoine , Knebelmann Bertrand , Salomon Rémi , Lyonnet Stanislas , Saunier Sophie , Burgun Anita 
Published: April 2020

Abstract
Introduction
Rare diseases affect approximately 350 million people worldwide. Delayed diagnosis is frequent due to lack of knowledge of most clinicians and a small number of expert centers. Consequently, computerized diagnosis support systems have been developed to address these issues, with many relying on rare disease expertise and taking advantage of the increasing volume of generated and accessible health-related data. Our objective is to perform a review of all initiatives aiming to support the diagnosis of rare diseases.

Methods
A scoping review was conducted based on methods proposed by Arksey and O’Malley. A charting form for relevant study analysis was developed and used to categorize data.

Results
Sixty-eight studies were retained at the end of the charting process. Diagnosis targets varied from 1 rare disease to all rare diseases. Material used for diagnosis support consisted mostly of phenotype concepts, images or fluids. Fifty-seven percent of the studies used expert knowledge. Two-thirds of the studies relied on machine learning algorithms, and one-third used simple similarities. Manual algorithms were encountered as well. Most of the studies presented satisfying performance of evaluation by comparison with references or with external validation. Fourteen studies provided online tools, most of which aimed to support the diagnosis of all rare diseases by considering queries based on phenotype concepts.

Conclusion
Numerous solutions relying on different materials and use of various methodologies are emerging with satisfying preliminary results. However, the variability of approaches and evaluation processes complicates the comparison of results. Efforts should be made to adequately validate these tools and guarantee reproducibility and explicability.
Challenges in recruiting and retaining adolescents with abuse-related posttraumatic stress disorder: lessons learned from a randomized controlled trial
Authors: Vogel Anna , Comtesse Hannah , Rosner Rita 
Published: April 2020

AbstractBackgroundResearch on effective recruitment and retention strategies for adolescents and young adults suffering from posttraumatic stress disorder is scarce. The aim of the current study was to provide data on recruitment sources, barriers, and facilitators for participation in a randomized controlled trial for young individuals with histories of sexual and/or physical abuse.MethodsStudy participants aged 14 to 21 were asked to complete a checklist on individual sources of recruitment, barriers, and facilitators for participation in the trial. Fifty-three out of the 80 study participants who were contacted completed the checklist (66.3%).ResultsMost respondents reported multiple recruitment sources, with online and media advertising search strategies indicated most frequently (45.4% of all mentions), followed by practitioner-referred sources (38.7%). Respondents’ reported barriers included additional demands of the trial (60.3%), followed by distress caused by having to talk about painful topics (15.5%). The most frequently indicated facilitators were the organizational setting (55.1%) and monetary incentives (22.2%), followed by social support (12.0%) and non-monetary incentives (10.2%). No significant differences were observed between adolescent and young adult respondents with the exception that adolescents reported significantly more frequently that they had learned about the trial from their caregiver.ConclusionsOur findings permit the formulation of recommendations for planning and conducting trials with this clientele. Future research is needed on how specific barriers can be effectively overcome.
What clinical crew competencies and qualifications are required for helicopter emergency medical services? A review of the literature
Authors: Masterson Siobhán , Deasy Conor , Doyle Mark , Hennelly David , Knox Shane , Sorensen Jan 
Published: April 2020

Abstract
Background
Patients served by Helicopter Emergency Medical Services (HEMS) tend to be acutely injured or unwell and in need of stabilisation followed by rapid and safe transport. It is therefore hypothesised that a particular clinical crew composition is required to provide appropriate HEMS patient care. A literature review was performed to test this hypothesis.

Methods
MEDLINE, EMBASE, Web of Science and the Cochrane Database of Systematic Reviews were systematically searched from 1 January 2009 to 30 August 2019 to identify peer-reviewed articles of relevance. All HEMS studies that mentioned ‘staffing’, ‘configuration’, ‘competencies’ or ‘qualifications’ in the title or abstract were selected for full-text review.

Results
Four hundred one studies were identified. Thirty-eight studies, including one systematic review and one randomised controlled trial, were included. All remaining studies were of an observational design. The vast majority of studies described clinical crews that were primarily doctor-staffed. Descriptions of non-doctor staff competencies were limited, with the exception of one paramedic-staffed model.

Conclusions
HEMS clinical crews tended to have a wider range of competencies and experience than ground-based crews, and most studies suggested a patient outcome benefit to HEMS provision. The conclusions that can be drawn are limited due to study quality and the possibility that the literature reviewed was weighted towards particular crewing models (i.e. primarily doctor-staffed) and countries. There is a need for trial-based studies that directly compare patient outcomes between different HEMS crews with different competencies and qualifications.