bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental fluoride neurotoxicity: an updated review
Authors: Grandjean Philippe 
Published: December 2019

Abstract
Background
After the discovery of fluoride as a caries-preventing agent in the mid-twentieth century, fluoridation of community water has become a widespread intervention, sometimes hailed as a mainstay of modern public health. However, this practice results in elevated fluoride intake and has become controversial for two reasons. First, topical fluoride application in the oral cavity appears to be a more direct and appropriate means of preventing caries. Second, systemic fluoride uptake is suspected of causing adverse effects, in particular neurotoxicity during early development. The latter is supported by experimental neurotoxicity findings and toxicokinetic evidence of fluoride passing into the brain.

Method
An integrated literature review was conducted on fluoride exposure and intellectual disability, with a main focus on studies on children published subsequent to a meta-analysis from 2012.

Results
Fourteen recent cross-sectional studies from endemic areas with naturally high fluoride concentrations in groundwater supported the previous findings of cognitive deficits in children with elevated fluoride exposures. Three recent prospective studies from Mexico and Canada with individual exposure data showed that early-life exposures were negatively associated with children’s performance on cognitive tests. Neurotoxicity appeared to be dose-dependent, and tentative benchmark dose calculations suggest that safe exposures are likely to be below currently accepted or recommended fluoride concentrations in drinking water.

Conclusion
The recent epidemiological results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. Recognition of neurotoxic risks is necessary when determining the safety of fluoride-contaminated drinking water and fluoride uses for preventive dentistry purposes.
LINC02273 drives breast cancer metastasis by epigenetically increasing AGR2 transcription
Authors: Xiu Bingqiu , Chi Yayun , Liu Lei , Chi Weiru , Zhang Qi , Chen Jiajian , Guo Rong , Si Jing , Li Lun , Xue Jingyan , Shao Zhi-Ming , Wu Zhao-Hui , Huang Shenglin , Wu Jiong 
Published: December 2019

AbstractBackgroundThe majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown.MethodslncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment.ResultsWe identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo.ConclusionsOur findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.
Further content validation of the 18-item NCCN/FACT Ovarian Symptom Index and its Disease Related Symptom-Physical (DRS-P) subscale for use in advanced ovarian cancer clinical trials
Authors: Shaunfield Sara , Jensen Sally , Fisher Allison P. , Webster Kimberly , Shahabi Shohreh , Ganguli Arijit , Cella David 
Published: December 2019

Abstract
Background
This study evaluated pre-defined aspects of content validity of the 18-item NCCN FACT-Ovarian Symptom Index (NFOSI-18) and its Disease-Related Symptoms-Physical (DRS-P) subscale, as clinical trial outcome tools for patients with advanced ovarian cancer.

Methods
Twenty-one women (mean age 59.5 years) diagnosed with advanced ovarian cancer completed the NFOSI-18 and participated in a cognitive interview to explore: (1) whether ‘pain’ and ‘cramps’ are considered redundant; (2) whether ‘fatigue’ and ‘lack of energy’ are overlapping concepts; (3) whether patients consider severity when responding to the item “I am bothered by constipation;” and (4) factors considered when responding to the item “I am sleeping well.” Interviews were audio-recorded, transcribed, and analyzed qualitatively.

Results
Pain was associated with discomfort, hurt, and life interference; ‘cramps’ was associated with pain, muscle tightening, and menstrual or digestive issues. Most (81%) considered the items “I have pain” and “I have cramps in my stomach area” to be more different than similar. Participants associated ‘fatigue’ with intense tiredness and ‘lack of energy’ with motivation and capability to complete daily activities. Item comparisons revealed a majority (65%) considered the items to be more different than similar. When responding to “I am bothered by constipation,” patients indicated constipation severity was related to bother. Finally, patients considered disease, treatment, and other factors when responding to “I am sleeping well.”

Conclusions
Findings support content validity of the NFOSI-18 and its DRS-P as originally constructed. We propose an alternative scoring option that excludes the item “I am sleeping well” from the DRS-P when used as a symptom-focused index for clinical research in a regulatory context.
Strengthening capacity to use research evidence in health sector policy-making: experience from Kenya and Malawi
Authors: Oronje Rose N. , Murunga Violet I. , Zulu Eliya M. 
Published: December 2019

Abstract
Background
Among the many barriers to evidence use in decision-making, weak capacity for evidence use has attracted a lot of focus in the last decade. The study aims to inform and enrich ongoing and future efforts to strengthen capacity for evidence use by presenting and discussing the experiences and lessons of a project implemented in Kenya and Malawi to strengthen individual and institutional capacity for evidence use within the ministries of health (MoHs).

Methods
This paper draws on the internal and external evaluations of a 3-year project funded by the United Kingdom’s Department for International Development, the Strengthening Capacity to Use Research Evidence in Health Policy (SECURE Health). To strengthen individual capacity, the project implemented a training and mentorship programme for 60 mid-level policy-makers in the two MoHs. To strengthen institutional capacity, the project conducted sustained advocacy with top leaders to strengthen structures that enable evidence-informed decision-making (EIDM), supported Kenya to develop research-for-health policies and priorities, supported Malawi to review the implementation of its health research agenda, developed EIDM guidelines for both MoHs, and supported bi-annual evidence dialogues to improve interactions and raise the profile of evidence. Internal evaluation included baseline and endline surveys (93 baseline and 92 endline interviews), 60 in-depth interviews, and intervention-specific evaluations (pre–post tests for training workshops, feedback forms for policy dialogues and tracking effects of advocacy efforts). The external evaluation was implemented alongside project implementation, conducting three annual evaluations.

Results
The results show that training and mentorship programmes in EIDM were effective in improving competencies of civil servants. However, such programmes need to train a critical mass to be effective in enhancing EIDM practice at the MoHs. On strengthening institutional capacity for EIDM, while the project achieved some success, it did not realise long-lasting effects because of its limited time of implementation and limited focus on sustained political economy analysis, which meant that the intervention was negatively affected by frequently changing interests within the MoHs.

Conclusions
Although training and mentorship are effective in improving EIDM competencies, they need to be incorporated in existing pre-service and in-service training programmes for sustainability. Strengthening institutional capacity for evidence use is complex and needs sustained political commitment and long-term investments.
EOS, an Ikaros family zinc finger transcription factor, interacts with the HTLV-1 oncoprotein Tax and is downregulated in peripheral blood mononuclear cells of HTLV-1-infected individuals, irrespective of clinical statuses
Authors: Naito Tadasuke , Ushirogawa Hiroshi , Fukushima Takuya , Tanaka Yuetsu , Saito Mineki 
Published: December 2019

Abstract
Background
EOS plays an important role in maintaining the suppressive function of regulatory T cells (Tregs), and induces a regulated transformation of Tregs into T helper-like cells, which are capable of secreting proinflammatory cytokines in response to specific inflammatory signals. Meanwhile, significant reduction in Treg activity along with production of proinflammatory cytokines has been reported in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Methods
In this study, to examine whether there is an alteration in EOS expression in peripheral blood mononuclear cells (PBMCs) derived from HTLV-1-infected individuals especially HAM/TSP, we investigated the expression of HTLV-1 tax genotype, proviral load (PVL), and the mRNA expression of tax, HBZ and EOS in HTLV-1 infected individuals including adult T-cell leukemia/lymphoma (ATL), HAM/TSP, or asymptomatic carriers. The expression levels of EOS mRNA and protein in various HTLV-1-infected or uninfected human T-cell lines were also investigated.

Results
EOS was highly expressed at the protein level in most HTLV-1 infected T-cell lines, and was augmented after the HTLV-1 regulatory factor Tax was induced in a Tax-inducible JPX-9 cell line. Immunoprecipitation experiments demonstrated a physical interaction between EOS and the viral regulatory protein Tax, but not HBZ. Meanwhile, there was a significant decrease in EOS mRNA levels in PBMCs of HTLV-1 infected individuals irrespective of their clinical statuses. We found an inverse correlation between EOS mRNA levels and HTLV-1 PVL in ATL patients, and positive correlations between both EOS mRNA load and PVL, and EOS and HBZ mRNA load in HAM/TSP patients, whereas this correlation was not observed in other clinical statuses.

Conclusions
These findings suggest that both Tax and HBZ can alter the expression of EOS through undetermined mechanisms, and dysregulated expression of EOS in PBMCs of HTLV-1 infected individuals may contribute to the pathological progression of HTLV-1-associated diseases, such as ATL and HAM/TSP.
Mental health profile and its relation with parental alcohol use problems and/or the experience of abuse in a sample of Moroccan high school students: an explorative study
Authors: Zouini Btissame , Sfendla Anis , Hedman Ahlström Britt , Senhaji Meftaha , Kerekes Nóra 
Published: December 2019

Abstract
Background
Studies on mental health are scarce from Arab countries, especially studies focusing on adolescents. In addition to the neurobiological and physiological changes that occur during adolescent development, psychological, societal and cultural influences have strong effects on adolescents’ behavior and on their somatic and mental health. The present study aimed (1) to describe the mental health profile, operationalized as psychological distress, of a sample of Moroccan adolescents, and (2) to investigate how specific psychosocial factors (parental alcohol use problems and the experience of physical and/or psychological abuse) may affect adolescents’ mental health.

Methods
The sample included 375 adolescents from conveniently selected classes of four high schools in the city of Tetouan in Morocco. The participants responded to an anonymous survey containing, beside other inventories, the Brief Symptom Inventory (BSI) and identified those reporting parental alcohol use problems and/or the previous experience of abuse. The sample characteristics were defined using descriptive statistics. The effects of the defined psychosocial factors were identified using the Kruskal–Wallis test, followed by the post hoc Fisher’s least significant difference test.

Results
The most common problems found in high school students from an urban region of Morocco were memory problems, concentration difficulties, restlessness, fear, nervosity and feelings of inadequacy during interpersonal interactions. The female students reported significantly higher psychological distress levels when compared to the male students (p < 0.001). The adolescents reporting parental alcohol use problems and the experience of physical/psychological abuse showed significantly higher levels of psychological distress (p = 0.02), especially symptoms of somatization (p < 0.001), hostility (p = 0.005) and anxiety (p = 0.01), than those not reporting any of these psychosocial factors.

Conclusion
The mental health profile of female adolescents from an urban area of Morocco is worse than that of their male fellow students. Adolescents reporting parental alcohol use problems and/or the experience of physical/psychological abuse need synchronized support from social- and healthcare services.
Improving blood product utilization at an ambulatory surgery center: a retrospective cohort study on 50 patients with lumbar disc replacement
Authors: Dorenkamp Benjamin C. , Janssen Madisen K. , Janssen Michael E. 
Published: December 2019

Abstract
Background
There is minimal literature discussing anterior lumbar spine surgery in ambulatory surgery centers (ASCs). The main concern with the anterior approach to the lumbar spine is the potential for injury to great vessels. In our facility, there are two units of crossmatched blood available in addition to cell saver during the procedure. We retrospectively looked at 50 cases of lumbar total disc arthroplasty (TDA) in our ASC to determine utilization of blood products.

Methods
Medical records of 50 consecutive patients who underwent a lumbar TDA at a single ASC were reviewed. Surgeries completed at the ASC were all transferred from the post anesthesia care unit to an attached convalescence care center which allows up to 3 days of observation. Patients who had either a 1 or 2 level lumbar TDA were included in the study. Data consisting of demographics, American Society of Anesthesiologist Physical Status Classification System, length of stay, estimated blood loss, cell saver volume, transfusion, perioperative and postoperative complications were recorded. Preoperative, perioperative and postoperative medical records were reviewed.

Results
Medical records of 50 consecutive patients were reviewed. The mean age was 40.86 ± 9.45. Of these, 48 (96%) had a 1-level lumbar TDA, 1(2%) had a 2-level lumbar TDA, 1 (2%) had a lumbar TDA at L4/5 and an anterior lumbar interbody fusion at L5/S1. There were no mortalities; no patient had recorded perioperative complications. No patients received allogeneic blood transfusion, 4 (8%) were re-transfused with cell saver (2 receiving approximately 400 ml and 2 receiving approximately 200 ml of re-transfused blood). All 50 (100%) were discharged home in stable condition. We had 30-day follow-up data on 35 of 50 patients. Of the 35 patients reviewed, three (8.5%) of the patients were readmitted to the hospital. One additional patient was seen in the emergency department and discharged home after negative testing. No patient was readmitted for post-operative anemia.

Conclusion
The routine use of both cell saver and crossmatched blood in the operating suite for lumbar TDA may be an over-utilization of healthcare resources. In our review of 50 patients, we had no need for transfusion of allogeneic packed red blood cells (PRBCs) and only four of the 50 patients had enough blood output for re-transfusion from the cell saver. This opens the conversation for alternatives to crossmatched PRBCs being held in the operating room. Such alternatives may be the use of cell salvage, only type O blood in a cooler for each patient or keeping type O blood on constant hold in ASCs.
A novel 14q13.1–21.1 deletion identified by CNV-Seq in a patient with brain-lung-thyroid syndrome, tooth agenesis and immunodeficiency
Authors: Hu Xuyun , Liu Jun , Guo Ruolan , Guo Jun , Zhao Zhipeng , Li Wei , Xu Baoping , Hao Chanjuan 
Published: December 2019

Abstract
Background
Chromosome 14q11-q22 deletion syndrome (OMIM 613457) is a rare genomic disorder. The phenotype heterogeneity depends on the deletion size, breakpoints and genes deleted. Critical genes like FOXG1, NKX2–1, PAX9 were identified.

Case presentation
We performed whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) for a patient with mild speech and motor developmental delay, short stature, recurrent pulmonary infections, tooth agenesis and triad of brain-lung-thyroid syndrome. By using CNV-seq, we identified a 3.1 Mb de novo interstitial deletion of the 14q13.2q21.1 region encompassing 17 OMIM genes including NKX2–1, PAX9 and NFKBIA. Our patient’s phenotype is consistent with other published 14q13 deletion patients.

Conclusion
Our results showed the combination of WES and CNV-seq is an effective diagnostic strategy for patients with genetic or genomic disorders. After reviewing published patients, we also proposed a new critical region for 14q13 deletion syndrome with is a more benign disorder compared to 14q11-q22 deletion syndrome.
Severe congenital RYR1-associated myopathy complicated with atrial tachycardia and sinus node dysfunction: a case report
Authors: Hayakawa Itaru , Abe Yuichi , Ono Hiroshi , Kubota Masaya 
Published: December 2019

Abstract
Background
Cardiac arrhythmias are sometimes encountered in patients with hereditary myopathies and muscular dystrophies. Description of arrhythmias in myopathies and muscular dystrophies is very important, because arrhythmias have a strong impact on the outcomes for these patients and are potentially treatable.

Case presentation
A girl with severe congenital RYR1-related myopathy exhibited atrial tachycardia and sinus node dysfunction during infancy. She was born after uncomplicated caesarian delivery. She showed no breathing, complete ophthalmoplegia, complete bulbar paralysis, complete facial muscle paralysis, and extreme floppiness. At 5 months old, she developed persistent tachycardia around 200–210 beats per minutes. Holter monitoring revealed ectopic atrial tachycardia during tachyarrhythmia and occasional sinus pauses with junctional escape beats. Propranolol effectively alleviated tachyarrhythmia but was discontinued due to increased frequency and duration of the sinus pauses that led to bradyarrhythmia. There was no evidence of structural heart diseases or heart failure. The arrhythmia gradually resolved spontaneously and at 11 months old, she showed complete sinus rhythm.

Conclusions
Although supraventricular arrhythmia is sometimes encountered in congenital myopathies, this is the first report of cardiac arrhythmia requiring drug intervention in RYR1-associated myopathy.
A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial
Authors:   On behalf of the CLEAR study group, Bradley Judy Martina , Anand Rohan , O’Neill Brenda , Ferguson Kathryn , Clarke Mike , Carroll Mary , Chalmers James , De Soyza Anthony , Duckers Jamie , Hill Adam T. , Loebinger Michael R. , Copeland Fiona , Gardner Evie , Campbell Christina , Agus Ashley , McGuire Alistair , Boyle Roisin , McKinney Fionnuala , Dickson Naomi , McAuley Danny F. , Elborn Stuart 
Published: December 2019

Abstract
Background
Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care.

Methods
This is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum.

Discussion
This trial’s pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE.

Trial registration
EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017).
ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018.
Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01).
Sponsor: Belfast Health and Social Care Trust.
Ethics Reference Number: 17/NE/0339.
Protocol version: v3.0 Final_14052018.
Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to activity management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): amendment to the published protocol
Authors: Anderson Emma , Gaunt Daisy , Metcalfe Chris , Rai Manmita , Hollingworth William , Mills Nicola , Beasant Lucy , Parslow Roxanne , Kessler David , Macleod John , Stallard Paul , Knoop Hans , Van de Putte Elise , Nijhof Sanne , Bleijenberg Gijs , Crawley Esther 
Published: December 2019

Abstract
The FITNET-NHS Trial is a UK, national, trial investigating whether an online cognitive behavioural therapy program (FITNET-NHS) for treating chronic fatigue syndrome/ME in adolescents is clinically effective and cost-effective in the NHS. At the time of writing (September 2019), the trial was recruiting participants. This article presents an update to the planned sample size and data collection duration previously published within the trial protocol.

Trial registration
ISRCTN, ID: 18020851. Registered 8 April 2016.