bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teacher Anxiety Program for Elementary Students (TAPES): intervention development and proposed randomized controlled trial
Authors: Ginsburg Golda S. , Pella Jeffrey E. , Piselli Kate , Chan Grace 
Published: December 2019

AbstractBackgroundExcessive student anxiety is a common problem that severely impairs short- and long-term academic functioning and increases teacher burden. Reducing student anxiety has been associated with improvement in educational functioning. Because anxiety manifests daily in the classroom, teachers are in an ideal position to identify and help students manage their anxiety. Unfortunately, teachers lack the knowledge and skills to support the learning of students with excessive anxiety. The Teacher Anxiety Program for Elementary Students (TAPES), a novel teacher-administered school-home collaborative intervention, was designed to address this gap.MethodsThis manuscript describes the protocol for developing and evaluating TAPES. Specifically, we present a description of: (1) the intervention and theoretical model; and (2) methods for the proposed randomized controlled trial comparing TAPES to a standard professional development seminar focused on reducing student anxiety.DiscussionPrimary aims examine the impact of the TAPES training on teacher knowledge and skill. Secondary aims examine the impact of TAPES on student outcomes. Exploratory aims will examine mediators based on our proposed theory of change. If effective, TAPES has the potential to directly benefit teachers (improving skills) and students (reducing anxiety and improving functioning).Trial registrationClinicalTrials.gov,NCT03899948. Registered on 28 March 2019.
Internet-based interpersonal psychotherapy for stress, anxiety, and depression in prenatal women: study protocol for a pilot randomized controlled trial
Authors: Bright Katherine S. , Mughal Muhammad Kashif , Wajid Abdul , Lane-Smith Marie , Murray Lindsay , Roy Nicola , Van Zanten Sander Veldhuyzen , Mcneil Deborah A. , Stuart Scott , Kingston Dawn 
Published: December 2019

Abstract
Background
Psychological distress, defined as depression, anxiety and perceived stress, during pregnancy is common, with 15–25% of women experiencing clinically significant levels of such distress. Despite the far-reaching impact of prenatal psychological distress on mothers and their children, and that women are receptive to screening, few providers routinely screen for prenatal psychological distress and less than one in five women will receive the mental health care that they require. There is a lack of certainty regarding the most effective treatments for prenatal psychological distress. No online interpersonal psychotherapy (IPT) trials have been conducted that focus on improving psychological distress in prenatal women. The purpose of this pilot randomized controlled trial is to evaluate the perspectives of pregnant women on the feasibility and acceptability of online IPT (e-IPT) delivered during pregnancy.

Methods
A pilot randomized controlled trial design with repeated measures will evaluate the feasibility and acceptability of e-IPT for pregnant women compared to routine prenatal care. Qualitative interviews with 15–30 individuals in the intervention group will provide further data on the feasibility and acceptability of the intervention. Assessment of feasibility will include the ease of accessing and completing the intervention. Women will also be asked about what barriers there were to starting and completing the e-IPT. Assessment of acceptability will inquire about the perception of women regarding the intervention and its various features. A sample size of 160 consenting pregnant women aged 18 years and older will be enrolled and randomized into the experimental (e-IPT) or control (routine care) condition. The secondary outcome measures include: depression, anxiety and stress symptoms; self-efficacy; self-mastery; self-esteem; relationship quality (spouse, immediate family members); coping; and resilience. All participants will complete the aforementioned measures at baseline during pregnancy (T1), 3 months postrandomization (T2), at 8 months of pregnancy (T3), and 3 months postpartum (T4).

Discussion
The results of this pilot randomized controlled trial will provide data on the feasibility and acceptability of the intervention and identify necessary adaptations. This study will allow for optimization of full trial processes and inform the evaluation strategy, including sample size calculations for the full randomized controlled trial.

Trial registration
ClinicalTrials.gov, NCT01901796. Registered on 18 December 2014.
The efficacy of iCBT added to treatment as usual for alcohol-dependent patients in primary care: study protocol for a randomized controlled trial
Authors: Hyland Karin , Hammarberg Anders , Hedman-Lagerlöf Erik , Johansson Magnus , Andreasson Sven 
Published: December 2019

Abstract
Background
Alcohol dependence is a common disorder with a continuum regarding severity. Most alcohol-dependent persons have a moderate level of dependence and live under socially orderly conditions. Treatment-seeking in this group is low, mainly due to stigma and because treatment options are seen as unappealing.
Alcohol is a relevant topic to discuss in many primary care (PC) consultations and PC is less stigmatizing to visit compared to addiction care units for people with alcohol problems. However, general practitioners (GPs) hesitate to engage in treating alcohol problems due to time constraints and lack of knowledge. Screening and brief interventions are effective for high consumers but there are few studies on dependence.

Methods
This is a two-group, parallel, randomized controlled trial (RCT). The aim is to study whether an Internet-based Cognitive Behavioral Treatment (iCBT) when added to treatment as usual (TAU) is more effective than TAU only for alcohol dependence in PC. Two hundred and sixty adults with alcohol dependence will be included. Participants are randomized to iCBT and TAU or TAU only. The primary study outcome is alcohol consumption in grams per week and heavy-drinking days. Secondary outcomes include alcohol-related problem severity, number of diagnostic criteria for alcohol dependence, depression and anxiety symptoms, health-related quality of life and biochemical markers for high consumption and liver pathology. Data will be analyzed using mixed-effect models.

Discussion
Internet-based interventions are attractive to, and have been shown to reach, people with alcohol problems. Yet there are no studies investigating the efficacy of Internet treatment of alcohol dependence in PC. In this study we hypothesize that iCBT when added to TAU will improve treatment outcome for alcohol dependence in PC, compared to TAU only. If effective, iCBT can be distributed to the public to a low cost for a stakeholder and has the opportunity to reduce both short-term and long-term public health costs.

Trial registration
ISRCTN69957414. Retrospectively registered on 7 June 2018.
Facile synthesis and antiproliferative activity of new 3-cyanopyridines
Authors: Abdel-aziz Hassan M. , Gomha Sobhi M. , El-Sayed Abdelaziz A. , Mabkhot Yahia Nasser , Alsayari Abdulrhman , Muhsinah Abdullatif Bin 
Published: December 2019

Abstract
Background
Pyridines have been reported to possess various pharmacological activities.

Results
Sodium 3-oxo-3-(2-oxo-2H-chromen-3-yl)prop-1-en-1-olate (2) and sodium 3-oxo-3-(3-oxo-3H-benzo[f]chromen-2-yl)prop-1-en-1-olate (7) were prepared and reacted with 2-cyano-N’-(1-aryl(heteryl)ethylidene)acetohydrazides 3a–d to produce 2-oxo-1,2-dihydropyridine-3-carbonitrile derivatives 5a–d and 9a–d, respectively, in good yields. Also, 3a–d reacted with sodium (2-oxocyclopentylidene)methanolate (11a) or sodium (2-oxocyclohexylidene) methanolate (11b) to yield 2-oxo-tetrahydro-1H-cyclopenta[b]pyridine-3-carbonitriles 13a–d and 2-oxo-hexahydroquinoline-3-carbonitriles 13e–h, respectively. The mechanisms that account for the formation of the products are discussed. Additionally, the structures of all the newly synthesized products are confirmed, based on elemental analysis and spectral data. Several of the newly synthesized compounds are evaluated for their antitumor activity against HEPG2 and their structure activity relationship (SAR) was studied.

Conclusions
The results revealed that the pyridine derivatives 5c and 5d (IC50 = 1.46, 7.08 µM, respectively) have promising antitumor activity against liver carcinoma cell line (HEPG2), compared to the reference drug, doxorubicin.
Neoantigen-specific immunity in low mutation burden colorectal cancers of the consensus molecular subtype 4
Authors: van den Bulk Jitske , Verdegaal Els M. E. , Ruano Dina , Ijsselsteijn Marieke E. , Visser Marten , van der Breggen Ruud , Duhen Thomas , van der Ploeg Manon , de Vries Natasja L. , Oosting Jan , Peeters Koen C. M. J. , Weinberg Andrew D. , Farina-Sarasqueta Arantza , van der Burg Sjoerd H. , de Miranda Noel F. C. C. 
Published: December 2019

Abstract
Background
The efficacy of checkpoint blockade immunotherapies in colorectal cancer is currently restricted to a minority of patients diagnosed with mismatch repair-deficient tumors having high mutation burden. However, this observation does not exclude the existence of neoantigen-specific T cells in colorectal cancers with low mutation burden and the exploitation of their anti-cancer potential for immunotherapy. Therefore, we investigated whether autologous neoantigen-specific T cell responses could also be observed in patients diagnosed with mismatch repair-proficient colorectal cancers.

Methods
Whole-exome and transcriptome sequencing were performed on cancer and normal tissues from seven colorectal cancer patients diagnosed with mismatch repair-proficient tumors to detect putative neoantigens. Corresponding neo-epitopes were synthesized and tested for recognition by in vitro expanded T cells that were isolated from tumor tissues (tumor-infiltrating lymphocytes) and from peripheral mononuclear blood cells stimulated with tumor material.

Results
Neoantigen-specific T cell reactivity was detected to several neo-epitopes in the tumor-infiltrating lymphocytes of three patients while their respective cancers expressed 15, 21, and 30 non-synonymous variants. Cell sorting of tumor-infiltrating lymphocytes based on the co-expression of CD39 and CD103 pinpointed the presence of neoantigen-specific T cells in the CD39+CD103+ T cell subset. Strikingly, the tumors containing neoantigen-reactive TIL were classified as consensus molecular subtype 4 (CMS4), which is associated with TGF-β pathway activation and worse clinical outcome.

Conclusions
We have detected neoantigen-targeted reactivity by autologous T cells in mismatch repair-proficient colorectal cancers of the CMS4 subtype. These findings warrant the development of specific immunotherapeutic strategies that selectively boost the activity of neoantigen-specific T cells and target the TGF-β pathway to reinforce T cell reactivity in this patient group.
A benchmark of transposon insertion detection tools using real data
Authors: Vendrell-Mir Pol , Barteri Fabio , Merenciano Miriam , González Josefa , Casacuberta Josep M. , Castanera Raúl 
Published: December 2019

Abstract
Background
Transposable elements (TEs) are an important source of genomic variability in eukaryotic genomes. Their activity impacts genome architecture and gene expression and can lead to drastic phenotypic changes. Therefore, identifying TE polymorphisms is key to better understand the link between genotype and phenotype. However, most genotype-to-phenotype analyses have concentrated on single nucleotide polymorphisms as they are easier to reliable detect using short-read data. Many bioinformatic tools have been developed to identify transposon insertions from resequencing data using short reads. Nevertheless, the performance of most of these tools has been tested using simulated insertions, which do not accurately reproduce the complexity of natural insertions.

Results
We have overcome this limitation by building a dataset of insertions from the comparison of two high-quality rice genomes, followed by extensive manual curation. This dataset contains validated insertions of two very different types of TEs, LTR-retrotransposons and MITEs. Using this dataset, we have benchmarked the sensitivity and precision of 12 commonly used tools, and our results suggest that in general their sensitivity was previously overestimated when using simulated data. Our results also show that, increasing coverage leads to a better sensitivity but with a cost in precision. Moreover, we found important differences in tool performance, with some tools performing better on a specific type of TEs. We have also used two sets of experimentally validated insertions in Drosophila and humans and show that this trend is maintained in genomes of different size and complexity.

Conclusions
We discuss the possible choice of tools depending on the goals of the study and show that the appropriate combination of tools could be an option for most approaches, increasing the sensitivity while maintaining a good precision.
Activating BRAF mutation in sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid gland: two case reports and review of the literature
Authors: Sukumar Jasmine S. , Sukumar Senthil , Purohit Darshana , Welch Brian J. , Balani Jyoti , Yan Shirley , Hathiramani Sumitha S. 
Published: December 2019

AbstractBackgroundSclerosing mucoepidermoid carcinoma with eosinophilia is a rare form of thyroid carcinoma. The underlying molecular mechanisms of sclerosing mucoepidermoid carcinoma with eosinophilia tumorigenesis remain unknown.Case presentationWe present two cases of sclerosing mucoepidermoid carcinoma with eosinophilia, both with a concurrent papillary thyroid carcinoma. Patient 1, a 70-year-old Caucasian woman, presented with sclerosing mucoepidermoid carcinoma with eosinophilia with distant renal metastasis and coexisting papillary thyroid carcinoma. Patient 2, a 74-year-old Caucasian woman with a remote history of thyroid cancer treated with thyroidectomy, presented with locoregionally invasive sclerosing mucoepidermoid carcinoma with eosinophilia and recurrent papillary thyroid carcinoma in the thyroid bed.BRAFmutation studies were performed on the sclerosing mucoepidermoid carcinoma with eosinophilia tumors. In both cases, sclerosing mucoepidermoid carcinoma with eosinophilia was positive for theBRAFV600E mutation by polymerase chain reaction. Patient 1 is the first reported case of sclerosing mucoepidermoid carcinoma with eosinophilia with renal metastasis, to the best of our knowledge.ConclusionsOur findings suggest, for the first time, to our knowledge, involvement of the RAS-RAF-MEK-ERK signaling pathway in the pathogenesis of sclerosing mucoepidermoid carcinoma with eosinophilia. Thus, BRAF inhibitors may prove to be a useful targeted medical therapy in the treatment of a subset of patients with aggressive sclerosing mucoepidermoid carcinoma with eosinophilia tumors who exhibitBRAFactivating mutation.
Buying efficiency: optimal hospital payment in the presence of double upcoding
Authors: Spika Simon B. , Zweifel Peter 
Published: December 2019

Abstract
Background
With DRG payments, hospitals can game the system by ’upcoding’ true patient’s severity of illness. This paper takes into account that upcoding can be performed by the chief physician and hospital management, with the extent of the distortion depending on hospital’s internal decision-making process. The internal decision making can be of the principal-agent type with the management as the principal and the chief physician as the agent, but the chief physicians may be able to engage in negotiations with management resulting in a bargaining solution.

Results
In case of the principal-agent mechanism, the distortion due to upcoding is shown to accumulate, whereas in the bargaining case it is avoided at the level of the chief physician.

Conclusion
In the presence of upcoding it may be appropriate for the sponsor to design a payment system that fosters bargaining to avoid additional distortions even if this requires extra funding.
Pharmacologic and surgical therapies for patients with Meniere’s disease: a protocol for a systematic review and meta-analysis
Authors: Ahmadzai Nadera , Cheng Wei , Wolfe Dianna , Bonaparte Jamie , Schramm David , Fitzpatrick Elizabeth , Lin Vincent , Skidmore Becky , Esmaeilisaraji Leila , Kilty Shaun , Hutton Brian 
Published: December 2019

Abstract
Background
Hearing loss is one of the leading causes of disability in Canada and worldwide, with more than one million Canadians enduring a hearing-related disability. Meniere’s disease (MD) is a chronic condition of the inner ear, manifesting as a triad of disabling symptoms, including attacks of vertigo, fluctuating sensorineural hearing loss (SNHL), and tinnitus. Impacts on quality of life are severe, particularly with respect to restrictions in social participation and physical activity, fatigue, and reduced capacity to work. Anxiety and other psychological disorders may result from the restrictions imposed on life, the constant uncertainty of vertigo attacks, and fluctuating SNHL, with neuroses and depression affecting 40 to 60% of sufferers of intractable MD. There is a need to establish the benefits of previously studied interventions with greater certainty. The planned systematic review and meta-analyses/network meta-analyses (NMAs) will assess the relative effects of competing pharmacologic and surgical interventions for management of MD in adults.

Methods
An experienced medical information specialist in consultation with the review team will develop the electronic search strategies. We will search various databases including MEDLINE, Embase, and the Cochrane Library with no date or language restrictions for published literature, and key clinical trial registries for in-progress and completed trials. Screening of the literature will be performed by two reviewers independently using pre-specified eligibility criteria, and quality of the included studies will be assessed using the Cochrane Risk of Bias tool. We will resolve disagreements through consensus or third-party adjudication. When applicable, meta-analyses and NMAs will be pursued to compare interventions in terms of their effects on outcomes, including frequency and severity of vertigo, occurrence and intensity of tinnitus, changes in hearing and speech recognition, quality of life, and harms. Separate analyses exploring the effects of pharmacologic and surgical approaches will be performed.

Discussion
Our planned systematic review will provide informative evaluations of existing treatments for management of Meniere’s disease. The findings will inform practitioners as to the relative benefits and harms of the existing competing interventions for MD, offer optimal clinical treatment strategies, identify evidence gaps, and determine promising therapies for evaluation in future trials.

Systematic review registration
PROSPERO CRD42019119129
Faucet aerators as a reservoir for Carbapenem-resistant Acinetobacter baumannii: a healthcare-associated infection outbreak in a neurosurgical intensive care unit
Authors: Lv Yu , Xiang Qian , Jin Ying Z. , Fang Ying , Wu Yu J. , Zeng Bin , Yu Hua , Cai Hong M. , Wei Qiong D. , Wang Chen , Chen Jing , Wang Hui 
Published: December 2019

Abstract
Background
On January 7, 2019, we observed an outbreak of healthcare-associated infection (HAI) caused by Carbapenem-resistant Acinetobacter baumannii (CRAB) in the neurosurgical intensive care unit (NSICU). A follow-up epidemiological investigation was conducted, and an emergency response was initiated. We aimed to study the clonal transmission of CRAB and its possible source.

Methods
A matched case-control (1:2) study was performed to identify the possible predisposing factors. A multifaceted intervention was implemented to control the outbreak. We collected environmental samples from patients’ rooms and living area of the staff. CRAB isolates were tested for genetic relatedness by Pulsed-Field Gel Electrophoresis (PFGE).

Results
Environmental sampling showed that a faucet aerator was contaminated with A. baumannii. Molecular typing revealed the only outbreak strain, which was isolated from tracheal aspirate cultures of the first case of community-acquired infection and 3 cases of HAI. In environmental samples, the outbreak strain was found only in the faucet aerator of the dining room. This CRAB outbreak was discovered in time, and further progress of this outbreak was prevented through a pre-set emergency response procedure.

Conclusions
The faucet aerator acted as a reservoir for bacteria in the outbreak, and contamination of the faucet aerator might have occurred from splashes originating from handwashing by the healthcare workers (HCWs). In high-risk areas, such as NSICU, the faucet aerators should not be used during an outbreak or they should be regularly cleaned and disinfected. The start-up criteria for the emergency response played a key role in controlling the CRAB outbreak, and its settings should be discussed more widely.
Implications of salep collection for the conservation of the Elder-flowered orchid (Dactylorhiza sambucina) in Epirus, Greece
Authors: Charitonidou Martha , Stara Kalliopi , Kougioumoutzis Konstantinos , Halley John M. 
Published: December 2019

AbstractBackgroundIn Epirus, Greece, orchids have been traditionally harvested for the production of salep, a beverage made from their tubers. Over-collection of orchids for salep is believed to be a growing threat to wild species, yet very little research has concentrated on orchid populations in the wild. Here, we studied the impact of salep collection on population demographic parameters and uniformity of distribution patterns of the Elder-flowered orchid,Dactylorhiza sambucina, the most commonly collected orchid in northern Greece.MethodsWe carried out fieldwork in four meadows where salep harvesting occurs, and conducted interviews in villages close to these sites. Fieldwork focused on the demographic parameters of orchid populations and on the characteristics of their habitat (natural-anthropogenic). We also measured population size and distribution, extent and multi-scale density, comparing distributions to Poisson and fractal models.ResultsAccording to interviews, salep collection by the local community has decreased, contrary to collection by people outside the community, which is increasing. Interviewees did not believe that orchid abundance was higher in the past; they claim that it can be very variable. None of the participants seemed aware of the legislation to conserve orchids. Demographic parameters did not seem to be strongly dependent on whether it was a harvested and non-harvested sites and population density was greatest in the site of highest collection pressure.ConclusionsOur findings show that salep collection is still ongoing in Epirus. Our interview results and our population study indicate that current levels of collection are not significantly affecting the abundance of the Elder-flowered orchid in Epirus subalpine meadows. However, the expanding commercial collection could reach levels that threaten the species. There is a need for a longer-term monitoring of these orchid populations, and a more effective modeling of the species’ response to different harvesting pressures.