bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal diagnosis of cri-du-chat syndrome by SNP array: report of twelve cases and review of the literature
Authors: Su Jiasun , Fu Huayu , Xie Bobo , Lu Weiliang , Li Wei , Wei Yuan , Zhang Qiang , Wei Shengkai , Chen Qiuli , Lu Yingchi , Jiang Tingting , Luo Jingsi , Qin Zailong 
Published: December 2019

Abstract
Background
Cri-du-chat syndrome (CdCS; OMIM#123450) is a classic contiguous gene syndrome caused by chromosome 5p terminal deletion (5p-), which characterized by a high-pitched cat-like cry, developmental delay, severe psychomotor, mental retardation, and dysmorphic features in infancy. Prenatal diagnosis of CdCS is difficult due to the non-specific ultrasound features. And reports using array analysis are rare. This study presented the first retrospective analysis of prenatal series of CdCS fetuses diagnosed by single nucleotide polymorphism (SNP) array in China.

Case presentation
A total of 35,233 pregnant women were enrolled from Jan 2014 to April 2019 in our center, there are twelve 5p- cases with abnormal sonographic signs revealed by SNP array, giving an incidence of 0.034% (12/35,233). Clinical information and molecular basis included: maternal demographics, indications for invasive testing, sonographic findings and SNP array results. Among all the 5p- cases revealed, nine cases were diagnosed by both karyotyping and SNP array, three cases were detected only by SNP array. Half of our cases (6/12) had an isolated 5p terminal deletion, which sizes ranged from 9.0 Mb to 30 Mb. The other half of cases (6/12) characterized by unbalanced translocation, with sex ratio 7:5 (female: male), when combine the clinical features observed from this study and available literature, the most frequent anomaly observed in prenatal ultrasound examination of CdCS was cerebral abnormalities, accounted for 44.4% (16/36) of the existing cases. Features that are less consistent included: choroid plexus cyst (13.8%, 5/36), single umbilical artery (13.3%, 4/30), ventricular septal defect (11.1%, 4/36), hydrops fetalis (8.3%, 3/36), ascites (8.3%, 3/36), increased NT/NF (8.3%, 3/36), absent/severely hypoplastic nasal bone (5.5%, 2/36), in order.

Conclusion
Prenatal findings such as cerebral abnormalities, absent/hypoplastic nasal bone, hydrops fetalis, ascites or encephalocele may act as suggestive signs of CdCS or other microdeletion/duplication syndromes. Combining typical karyotyping with chromosomal microarray analysis (CMA) is a definitive method for a precise diagnosis of CdCS and provides more accurate results in order to offer genetic counseling to families which need to deal with cryptic aberrations.
Zinc transporters in Alzheimer’s disease
Authors: Xu Yingshuo , Xiao Guiran , Liu Li , Lang Minglin 
Published: December 2019

AbstractAlzheimer’s disease (AD) is the most devastating neurodegenerative disorder. Due to the increase in population and longevity, incidence will triple by the middle of the twenty-first century. So far, no treatment has prevented or reversed the disease. More than 20 years of multidisciplinary studies have shown that brain zinc dyshomeostasis may play a critical role in AD progression, which provides encouraging clues for metal-targeted therapies in the treatment of AD. Unfortunately, the pilot clinical application of zinc chelator and/or ionophore strategy, such as the use of quinoline-based compounds, namely clioquinol and PBT2, has not yet been successful. The emerging findings revealed a list of key zinc transporters whose mRNA or protein levels were abnormally altered at different stages of AD brains. Furthermore, specifically modulating the expression of some of the zinc transporters in the central nervous system through genetic methods slowed down or prevented AD progression in animal models, resulting in significantly improved cognitive performance, movement, and prolonged lifespan. Although the underlying molecular mechanisms are not yet fully understood, it shed new light on the treatment or prevention of the disease. This review considers recent advances regarding AD, zinc and zinc transporters, recapitulating their relationships in extending our current understanding of the disease amelioration effects of zinc transport proteins as potential therapeutic targets to cure AD, and it may also provide new insights to identify novel therapeutic strategies for ageing and other neurodegenerative diseases, such as Huntington’s and Parkinson’s disease.
Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer
Authors: Wang Hongbo , Lu Zaiming , Zhao Xiangxuan 
Published: December 2019

AbstractHepatocellular carcinoma (HCC, also called primary liver cancer) is one of the most fatal cancers in the world. Due to the insidiousness of the onset of HCC and the lack of effective treatment methods, the prognosis of HCC is extremely poor, and the 5-year average survival rate is less than 10%. Exosomes are nano-sized microvesicle and contain various components such as nucleic acids, proteins, and lipids. Exosomes are important carriers for signal transmission or transportation of material from cell to cell or between cells and tissues. In recent years, exosomes have been considered as potential therapeutic targets of HCC. A large number of reports indicate that exosomes play a key role in the establishment of an HCC microenvironment, as well as the development, progression, invasion, metastasis, and even the diagnosis, treatment, and prognosis of HCC. However, the exact molecular mechanisms and roles of exosomes in these processes remain unclear. We believe that elucidation of the regulatory mechanism of HCC-related exosomes and its signaling pathway and analysis of its clinical applications in the diagnosis and treatment of HCC can provide useful clues for future treatment regimens for HCC. This article discusses and summarizes the research progress of HCC-related exosomes and their potential clinical applications.
RETRACTED ARTICLE: m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis
Authors: Jin Dan , Guo Jiwei , Wu Yan , Du Jing , Yang Lijuan , Wang Xiaohong , Di Weihua , Hu Baoguang , An Jiajia , Kong Lingqun , Pan Lei , Su Guoming 
Published: December 2019

Abstract
Background
METTL3 is an RNA methyltransferase that mediates m6A modification and is implicated in mRNA biogenesis, decay, and translation. However, the biomechanism through which METTL3 regulates MALAT1-miR-1914-3p-YAP axis activity to induce NSCLC drug resistance and metastasis is not very clear.

Methods
The expression of mRNA was analyzed by qPCR assays. Protein levels were analyzed by western blotting and immunofluorescent staining. Cellular proliferation was detected by CCK8 assays. Cell migration and invasion were analyzed by wound healing and transwell assays, respectively. Promoter activities and gene transcription were analyzed by luciferase reporter assays. Finally, m6A modification was analyzed by MeRIP.

Results
METTL3 increased the m6A modification of YAP. METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. Moreover, the RNA level of MALAT1 was increased due to a higher level of m6A modification mediated by METTL3. Meanwhile, the stability of MALAT1 was increased by METTL3/YTHDF3 complex. Additionally, MALAT1 functions as a competing endogenous RNA that sponges miR-1914-3p to promote the invasion and metastasis of NSCLC via YAP. Furthermore, the reduction of YAP m6A modification by METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.

Conclusion
Results indicated that the m6A mRNA methylation initiated by METTL3 promotes YAP mRNA translation via recruiting YTHDF1/3 and eIF3b to the translation initiation complex and increases YAP mRNA stability through regulating the MALAT1-miR-1914-3p-YAP axis. The increased YAP expression and activity induce NSCLC drug resistance and metastasis.
miR-552 promotes ovarian cancer progression by regulating PTEN pathway
Authors: Zhao Wenman , Han Tao , Li Bao , Ma Qianyun , Yang Pinghua , Li Hengyu 
Published: December 2019

Abstract
Background
Increasing researches have demonstrated the critical functions of MicroRNAs (miRNAs) in the progression of malignant tumors, including ovarian cancer. It was reported that miR-552 was an important oncogene in both breast cancer and colorectal cancer. However, the role of miR-552 in ovarian cancer (OC) remains to be elucidated.

Methods
RT-PCR and western blot analysis were used to detect the expression of miR-552 and PTEN. The impact of miR-552 on ovarian cancer proliferation and metastasis was investigated in vitro. The prognostic value of miR-552 was evaluated using the online bioinformatics tool Kaplan-Meier plotter.

Results
In the present study, we for first found that miR-552 was upregulated in ovarian cancer, especially in metastatic and recurrence ovarian cancer. Forced miR-552 expression promotes the growth and metastasis of ovarian cancer cells. Consistently, miR-552 interference inhibits the proliferation and metastasis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified Phosphatase and tension homolog (PTEN) as a direct target of miR-552. miR-552 downregulated the PTEN mRNA and protein expression in ovarian cancer cells. Furthermore, the PTEN siRNA abolishes the discrepancy of growth and metastasis capacity between miR-552 mimic ovarian cells and control cells. More importantly, upregulation of miR-552 predicts the poor prognosis of ovarian cancer patients.

Conclusion
Our findings revealed that miR-552 could promote ovarian cancer cells progression by targeting PTEN signaling and might therefore be useful to predict patient prognosis.
Effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory biomarkers, tumor marker CEA, and nutritional status in patients with colorectal cancer: a study protocol for a double blind randomized controlled trial
Authors: Haidari Fatemeh , Abiri Behnaz , Iravani Masood , Razavi Seyed-Mohsen , Sarbakhsh Parvin , Ahmadi-Angali Kambiz , Vafa Mohammadreza 
Published: December 2019

AbstractBackgroundMuch evidence is available demonstrating that both vitamin D and omega-3 fatty acids block the development and progression of colonic carcinogenesis. The results of animal studies have shown that the consumption of omega-3 fatty acids can decrease inflammatory biomarkers, enhance the efficacy of chemotherapy, and decrease the side effects of chemotherapy or cancer. Also, observational studies propose that higher levels of 25(OH)D are related to improved survival of colorectal cancer patients. This study will aim to evaluate the effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory biomarkers, tumor marker CEA, and nutritional status in colorectal cancer patients.Methods/designWe will carry out an 8-week double-blind randomized, placebo-controlled clinical trial to evaluate the effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory biomarkers, tumor marker CEA, and nutritional status in patients with stage ӀӀ or ӀӀӀ colorectal cancer undergoing chemotherapy.DiscussionBecause of the important effects of vitamin D and omega-3 fatty acids on molecular pathways involved in cancer development and progression, it seems that both vitamin D and omega-3 fatty acids may provide a new adjuvant therapy by decreasing inflammatory biomarkers and resistance to cancer treatment in patients with colorectal cancer.Trial registrationIranian Registry of Clinical TrialsIRCT20180306038979N1. Registered on 16 March 2018.
A pragmatic pilot phase II randomised controlled trial of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) in adult patients who are undergoing heart surgery (PROPHESY)
Authors: Green Laura , Roberts Neil , Cooper Jackie , Field Jane , Gill Ravi , Klein Andrew , Agarwal Seema , Stanworth Simon , Johnston Atholl , Monk Vivienne , O’Brien Ben 
Published: December 2019

Abstract
Background
Fresh frozen plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during or immediately after cardiac surgery. In the United Kingdom prothrombin complex concentrate (PCC) is not licensed in this setting, although it is being used in Europe because it has a higher concentration of clotting factor levels, and it can be administered rapidly and in small volume, resulting in less volume overload during cardiac surgery.

Methods
PROPHESY is a pragmatic, single-centre, open-label, randomised, controlled pilot trial that will assess whether it is feasible to perform a large trial in the future that will compare PCC versus FFP in patients who are bleeding (not on warfarin) and who require blood transfusion. Over a 15-month period, 50 patients will be randomised to PCC versus FFP if they develop active bleeding within 24 h of cardiac surgery and for whom the clinician has decided to administer FFP for treatment of bleeding. Standard laboratory and point-of-care assessments will be performed as per routine practice, and additional research blood samples will be taken at three time points to assess haemostasis. Subjects will be assessed daily up to hospital discharge or 30 days or death (whichever occurs first) and will be seen in follow-up for 90 days after surgery to assess for thromboembolic complications and hospital re-admission since discharge. Quality-of-life assessment will be performed pre-surgery and at 90 days post-surgery. We will also perform qualitative research with clinical experts and patients to explore the understanding of and experience with the interventions, as well as adherence to study procedures and protocol.

Discussion
There have been no randomised controlled trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery patients who are bleeding. This pilot study will assess if individual components of a large trial are deliverable to assess the safety and efficacy of the two blood products in the future.

Trial registration
EudraCT, 2018-003041-41; ClinicalTrials.gov, NCT03715348. Registered on 29 July 2018.
The effect of antibiotics on post-adenotonsillectomy morbidity in Tanzanian children: study protocol for a randomized, double-blind, placebo-controlled trial
Authors: Katundu Denis R. , Shija Peter S. , Nyombi Baltazari , Semvua Hadija , Oussoren Fieke K. , van Heerbeek Niels 
Published: December 2019

Abstract
Background
Adenotonsillectomy is the most frequently performed operation in children worldwide. For decades, prophylactic antibiotics have been prescribed to limit postoperative complications. The effect of this antibiotic use has been refuted in a Cochrane Review. However, all reviewed studies were carried out in developed countries. In Tanzania, like many other developing countries with limited resources and a high burden of infectious diseases, postoperative antibiotic prescription is still very common to decrease the supposed higher postoperative morbidity. However, as a consequence of this widespread use of postoperative antibiotics, cross-resistance and risk of allergic side effects rise. Well-designed randomized controlled trials are needed to limit unnecessary antibiotic prescription and secondary antibiotic resistance.

Aim
The aim of this study is to analyse the prophylactic role of postoperative antibiotics on morbidity following adenotonsillectomy in children in Tanzania.

Design
The double-blinded, randomized, placebo-controlled trial was set in northern Tanzania. Participating centres are the Department of Otolaryngology at Kilimanjaro Christian Medical Centre in Moshi and the Department of Paediatric Surgery at the Arusha Lutheran Medical Centre in Arusha.

Methods
Around 270 children aged 2–14 years, all scheduled for elective (adeno)tonsillectomy, will be included and assigned to receive either a standard regimen of 5 days of antibiotic prophylaxis or placebo after surgery. The primary outcomes are postoperative haemorrhage, fever and pain. Secondary outcomes are the time until normal diet is resumed, the time until normal activities are resumed and the occurrence of adverse events and microbial recolonization of the tonsillar beds.

Discussion
This study will enhance an increase of proper antimicrobial prescription in Tanzanian institutions as well as other resource-limited countries where prescription of antibiotics is still very common. In addition, it might augment current knowledge about surface and core tonsillar micro-organisms and sensitivity patterns.

Trial registration
Pan African Clinical Trials Registry, PACTR201905466349317. Retrospectively registered on 15 May 2019. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=8119
Principles and procedures for data and safety monitoring in pragmatic clinical trials
Authors: Simon Gregory E. , Shortreed Susan M. , Rossom Rebecca C. , Penfold Robert B. , Sperl-Hillen Jo Ann M. , O’Connor Patrick 
Published: December 2019

Abstract
Background
All clinical trial investigators have ethical and regulatory obligations to monitor participant safety and trial integrity. Specific procedures for meeting these obligations, however, may differ substantially between pragmatic trials and traditional explanatory clinical trials.

Methods/Results
Appropriate monitoring of clinical trials typically includes assessing rate of recruitment or enrollment; monitoring safe and effective delivery of study treatments; assuring that study staff act to minimize risks; monitoring quality and timeliness of study data; and considering interim analyses for early detection of benefit, harm, or futility. Each of these responsibilities applies to pragmatic clinical trials. Just as design of pragmatic trials typically involves specific and necessary departures from methods of explanatory clinical trials, appropriate monitoring of pragmatic trials typically requires specific departures from monitoring procedures used in explanatory clinical trials. We discuss how specific aspects of pragmatic trial design and operations influence selection of monitoring procedures and illustrate those choices using examples from three ongoing pragmatic trials conducted by the Mental Health Research Network.

Conclusions
Pragmatic trial investigators should not routinely adopt monitoring procedures used in explanatory clinical trials. Instead, investigators should consider core principles of trial monitoring and design monitoring procedures appropriate for each pragmatic trial.
Association of age, sex and BMI with the rate of change in tibial cartilage volume: a 10.7-year longitudinal cohort study
Authors: Cai Guoqi , Jiang Matthew , Cicuttini Flavia , Jones Graeme 
Published: December 2019

Abstract
Background
To describe the association of age, sex and body mass index with the rate of change of tibial knee cartilage volume over 10.7 years in a community-based sample of older adults.

Methods
Four hundred and eighty-one participants (49% female, mean age 60.8 years [range 51.1–79.7], 49% had knee pain and 58% radiographic osteoarthritis) were included. Tibial cartilage volume of the right knee was assessed on T1-weighted fat-suppressed 1.5 T MRI at baseline and 10.7 years. Data analyses were performed using linear regression models.

Results
The average rate of loss of cartilage volume was 1.2%/year (range 0.2–3.9%) with all participants losing cartilage volume over the study period. There was a significant association between age and loss of tibial cartilage volume in the medial (0.023%/year, 95% confidence interval [CI] 0.010 to 0.036%, p < 0.001), lateral (0.013%/year, 95% CI 0.003 to 0.023%, p = 0.012) and total tibia (0.018%/year, 95% CI 0.009 to 0.026%, p < 0.001). Higher body mass index at baseline and increases in body mass index over time were associated with a greater tibial cartilage loss at the medial (body mass index at baseline 0.040%/year, 95% CI 0.022 to 0.058%, p < 0.001; increases in body mass index 0.055%/year, 95% CI 0.018 to 0.093%, p = 0.004) but not lateral compartment. No evidence of non-linear relationships was observed. Compared to males, females lost more lateral tibial cartilage with increasing age (0.023%/year, 95% CI 0.003 to 0.043%, p = 0.024 for interaction).

Conclusions
Tibial cartilage volume declines at a faster rate with increasing age and body mass index in both males and females, particularly in the medial compartment. In contrast to the low rate of change in radiographs, our findings suggest that cartilage loss at the tibia is universal in this age group.
Quantification and Modeling of the Interactions of Gamma Radiation with Concrete from Bulk-Scale Observations
Authors: Reches Yonathan 
Published: December 2019

AbstractThe exposure of concrete to gamma radiation gives rise to a set of physical and chemical processes over multiple length scales, from molecular to bulk. The literature includes a number of bulk-scale studies which report the radiogenic heating of concrete and the loss of water (unbound, physically-bound, and/or chemically-bound) due to irradiation. This paper mechanistically quantifies observations by these studies, and presents a continuum framework to model the effects of gamma photons on concrete. A basis is presented for comparing otherwise disparate results in the literature for radiolysis rates. The Stefan–Boltzmann Law, adapted to include a gamma heat source term, reasonably describes radiogenic heating in concrete specimens. In multiple studies, the primary mechanism for dehydration is the loss of liquid water in the pore network of the cement product, rather than of water which is physically or chemically bound in a solid state.
Performance of proximity loggers under controlled field conditions: an assessment from a wildlife ecological and epidemiological perspective
Authors: Triguero-Ocaña Roxana , Vicente Joaquín , Acevedo Pelayo 
Published: December 2019

Abstract
Background
Ecological sciences have, in recent decades, benefited from the ability of proximity loggers (PLs)—i.e. devices that transmit and receive radio signals (UHF)—to quantify intra- and inter-specific interactions. These are used to estimate the frequency of contacts according to a predefined distance between individuals or between individuals and environmental features. The performance of these devices may, however, be potentially affected by several factors, signifying that they require accurate calibration under field conditions in order to correctly interpret the information obtained. We assessed the effect of four relevant factors in ecological and epidemiological studies over the attenuation of radio waves in terms of the received signal strength indicator (RSSI) and contact success rate at a short (3 m) and medium distance (up to 20 m). The factors considered were: height above the ground (0–1 m), the presence/absence of vegetation, the presence/absence of live body mass around the devices, the distance between devices and the overlaid effects of all of them.

Results
The RSSI was found to be an accurate measure of distance, although its precision decreased over greater distances (up to 100 m), with the loss being sharper with vegetation, with body mass and when the devices were located on the ground. The success rate at up to 20 m decreased with distance and was also affected by body mass and vegetation. A probability of contact success of 81% was obtained in the best conditions (without vegetation and body mass) at a distance of 3 m, whereas it was of 56% in the worst conditions.

Conclusions
Our study shows the potential synergistic effects of external factors on the performance of PLs, even when they are used to infer near-contacts. We, therefore, highlight the importance of assessing, for each particular study, the combined effect of non-controllable external factors on the performance of PLs in order to estimate the minimum (best scenario) and maximum (worst scenario) level of underestimation in the field data. The sampling design described here is a cost-effective protocol suitable for this purpose.