bluuebunny/crossref_metadata_2025_split huggingface dataset:
BET bromodomain inhibitors PFI-1 and JQ1 are identified in an epigenetic compound screen to enhance C9ORF72 gene expression and shown to ameliorate C9ORF72-associated pathological and behavioral abnormalities in a C9ALS/FTD model
Authors: Quezada Esteban , Cappelli Claudio , Diaz Iván , Jury Nur , Wightman Nicholas , Brown Robert H. , Montecino Martín , van Zundert Brigitte 
Published: March 2021

AbstractBackgroundAn intronic GGGGCC (G4C2) hexanucleotide repeat expansion (HRE) in theC9ORF72gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), referred to as C9ALS/FTD. No cure or effective treatment exist for C9ALS/FTD. Three major molecular mechanisms have emerged to explain C9ALS/FTD disease mechanisms: (1) C9ORF72 loss-of-function through haploinsufficiency, (2) dipeptide repeat (DPR) proteins mediated toxicity by the translation of the repeat RNAs, and more controversial, (3) RNA-mediated toxicity by bidirectional transcription of the repeats that form intranuclear RNA foci. Recent studies indicate a double-hit pathogenic mechanism in C9ALS/FTD, where reduced C9ORF72 protein levels lead to impaired clearance of toxic DPRs. Here we explored whether pharmacological compounds can revert these pathological hallmarks in vitro and cognitive impairment in a C9ALS/FTD mouse model (C9BAC). We specifically focused our study on small molecule inhibitors targeting chromatin-regulating proteins (epidrugs) with the goal of increasingC9ORF72gene expression and reduce toxic DPRs.ResultsWe generated luciferase reporter cell lines containing 10 (control) or ≥ 90 (mutant) G4C2 HRE located between exon 1a and 1b of the humanC9ORF72gene. In a screen of 14 different epidrugs targeting bromodomains, chromodomains and histone-modifying enzymes, we found that several bromodomain and extra-terminal domain (BET) inhibitors (BETi), including PFI-1 and JQ1, increased luciferase reporter activity. Using primary cortical cultures from C9BAC mice, we further found that PFI-1 treatment increased the expression of V1-V3 transcripts of the human mutantC9ORF72gene, reduced poly(GP)-DPR inclusions but enhanced intranuclear RNA foci. We also tested whether JQ1, an BETi previously shown to reach the mouse brain by intraperitoneal (i.p.) injection, can revert behavioral abnormalities in C9BAC mice. Interestingly, it was found that JQ1 administration (daily i.p. administration for 7 days) rescued hippocampal-dependent cognitive deficits in C9BAC mice.ConclusionsOur findings place BET bromodomain inhibitors as a potential therapy for C9ALS/FTD by amelioratingC9ORF72-associated pathological and behavioral abnormalities. Our finding that PFI-1 increases accumulation of intranuclear RNA foci is in agreement with recent data in flies suggesting that nuclear RNA foci can be neuroprotective by sequestering repeat transcripts that result in toxic DPRs.
Gamma heavy chain disease associated with rheumatoid arthritis: a case report
Authors: Danic Gwenvaël , Dejoie Thomas , Caillon Hélène , Achille Aurélie , Pottier Pierre , Agard Christian 
Published: March 2021

Abstract
Background
Gamma heavy chain disease (γ-HCD) is a monoclonal gammopathy defined by an abnormal clonal and isolated production of incomplete heavy chain gamma (γ), unable to bind with light chains kappa or lambda. This disease is rare and remains poorly described. Its association to lymphoid neoplasm is well established, but exceptional forms of γ-HCD may also accompany auto-immune diseases. We report here a new case of γ-HCD characterized by an indolent course with a 4-year follow-up, and its association with quiescent rheumatoid arthritis (RA).

Case presentation
We report the case of a 85-year old French white man followed for quiescent anti-CCP+ rheumatoid arthritis treated by prednisolone 4 mg/day and hydroxychloroquine 200 mg/day since 10 years, and a monoclonal gammopathy of undetermined significance for 6 years, who was hospitalized for costal fractures after a fall. Serum protein electrophoresis showed a stable small monoclonal peak, and capillary electrophoresis/immunosubtraction technique identified an isolated clonal γ-heavy chain (HC). Bone marrow aspiration was normal and he had no other lymphoproliferation. The monoclonal peak remained stable after 4 years of follow-up.

Conclusions
In case of monoclonal peak without complete monoclonal Ig on serum protein electrophoresis, the diagnosis of γ-HCD should be discussed and capillary electrophoresis/immune-subtraction is a mean to detect isolated monoclonal heavy chain (HC). Gamma-HC disease is rare, may be associated to RA, and may have an indolent course.
Learning chemistry: exploring the suitability of machine learning for the task of structure-based chemical ontology classification
Authors: Hastings Janna , Glauer Martin , Memariani Adel , Neuhaus Fabian , Mossakowski Till 
Published: March 2021

AbstractChemical data is increasingly openly available in databases such as PubChem, which contains approximately 110 million compound entries as of February 2021. With the availability of data at such scale, the burden has shifted to organisation, analysis and interpretation. Chemical ontologies provide structured classifications of chemical entities that can be used for navigation and filtering of the large chemical space. ChEBI is a prominent example of a chemical ontology, widely used in life science contexts. However, ChEBI is manually maintained and as such cannot easily scale to the full scope of public chemical data. There is a need for tools that are able to automatically classify chemical data into chemical ontologies, which can be framed as a hierarchical multi-class classification problem. In this paper we evaluate machine learning approaches for this task, comparing different learning frameworks including logistic regression, decision trees and long short-term memory artificial neural networks, and different encoding approaches for the chemical structures, including cheminformatics fingerprints and character-based encoding from chemical line notation representations. We find that classical learning approaches such as logistic regression perform well with sets of relatively specific, disjoint chemical classes, while the neural network is able to handle larger sets of overlapping classes but needs more examples per class to learn from, and is not able to make a class prediction for every molecule. Future work will explore hybrid and ensemble approaches, as well as alternative network architectures including neuro-symbolic approaches.
Calf health from birth to weaning - an update
Authors: Lorenz Ingrid 
Published: March 2021

AbstractResearch on calf health and welfare has intensified in the past decades. This is an update on a review series on calf health from birth to weaning published ten years ago.Good colostrum management is still recognised as the single most important factor to preventing calf morbidity and mortality, however, it is now known that immunoglobulins are only one of many components of colostrum that are vital for the calf’s development. Other non-nutrient factors like leucocytes, hormones and growth factors, oligosaccharides as well as microRNAs have significant effects on the development and maturation of the intestinal and systemic immune functions. They also promote the maturation and function of the intestine, thus enabling the calf to digest and absorb the nutrients provided with colostrum and milk. The improved energetic status of colostrum-fed neonates is reflected by an accelerated maturation of the somatotropic axis, which stimulates body growth and organ development. Colostrum oligosaccharides are presumed to play a major role in the development of a healthy intestinal flora.A biologically normal (intensive) milk-feeding programme is subsequently necessary for optimal body growth, organ development and resistance to infectious diseases. Ad-libitum or close to ad-libitum feeding in the first three to four weeks of life also leaves calves less hungry thus improving calf welfare. Only calves fed intensively with colostrum and milk are able to reach their full potential for performance throughout their life.Public interest in farm animal welfare is growing in past decades, which makes it necessary to have a closer look at contentious management practices in the dairy industry like early separation of the dairy calf from the dam with subsequent individual housing. Public objection to these practices cannot be mitigated through educational efforts. Contrary to common opinion there is no evidence that early cow-calf separation is beneficial for the health of calf or cow. There is evidence of behavioural and developmental harm associated with individual housing in dairy calves, social housing improves feed intake and weight gains, and health risks associated with grouping can be mitigated with appropriate management.In conclusion, there are still many management practices commonly applied, especially in the dairy industry, which are detrimental to health and welfare of calves.
Motivational network intervention to reduce substance use and increase supportive connections among formerly homeless emerging adults transitioning to housing: study protocol for a pilot randomized controlled trial
Authors: Tucker Joan S. , Kennedy David P. , Osilla Karen Chan , Golinelli Daniela 
Published: March 2021

Abstract
Background
Studies indicate high rates of substance use among youth experiencing homelessness (YEH). Further, the social networks of YEH, although multi-dimensional in composition, are largely comprised of other YEH, substance users, and individuals who do not provide the youth with tangible or emotional support. For YEH who have the opportunity to enter a housing program, helping them to reduce their substance use and strengthen their prosocial supportive connections during this critical transition period may increase their stability and reduce their risk of re-entering homelessness. The goal of this study is to pilot test a brief motivational network intervention (MNI), delivered by case managers, to help former YEH who have recently transitioned to a housing program reduce their substance use and strengthen their prosocial supportive connections.

Methods/design
Up to 60 residents of housing programs in the Los Angeles area will be randomized to receive four sessions of usual case manager support or four sessions of case manager support + MNI. Each MNI session consists of three parts: (1) identifying two goals that are most important for the resident over the next year (e.g., get or keep a job, finish or stay in school, reduce substance use); (2) a network interview with the resident to capture network data pertaining to their interactions in the past 2 weeks; and (3) a discussion between the case manager and the resident of the resulting network visualizations, conducted in a Motivational Interviewing (MI) style, and what role the resident’s network may play in reaching their most important goals over the next year.

Discussion
This study addresses a critical gap by pilot testing a computer-assisted MNI, delivered using MI techniques, that can help case managers work with recent YEH to reduce substance use and increase permanent supportive connections during the critical transitional period from homelessness to housing.
Trial registration ClinicalTrials.gov Identifier: NCT04637815. Registered November 10, 2020.
The subtle nuances of intranasal corticosteroids
Authors: Fowler James , Rotenberg Brian W. , Sowerby Leigh J. 
Published: March 2021

Background In the specialty of Otolaryngology – Head and Neck Surgery, intranasal corticosteroids are the mainstay treatment for inflammatory processes within the nasal cavity. All too often, physician prescribing patterns are based on previous training, personal experience, and interactions with industry. The purpose of this commentary is to review the nuances of each intranasal corticosteroid. Commentary There are nine intranasal corticosteroids approved for use in Canada. Each are discussed in detail, including their indication, bioavailability, effects on intranasal environment, and factors around patient adherence. Off-label use of budesonide irrigations is also discussed and cost information is presented in reference format for all available intranasal corticosteroids. Conclusion Although the efficacy of each intranasal corticosteroid has been shown to be similar, prescribing should be tailored based on bioavailability, intranasal environment, and factors that impact patient adherence such as dosing, cost and tolerability. Graphical abstract
Towards a science inquiry test in primary education: development of items and scales
Authors: Pedaste Margus , Baucal Aleksandar , Reisenbuk Elle 
Published: March 2021

Abstract
Background
Inquiry-based learning is widely applied in science education; however, so far, the outcomes of learning process have been systematically assessed mainly at the secondary school level. For primary school students, there is no valid instrument for assessing the outcomes of their science inquiry. The aim of the current study was to develop a test for assessing science learning outcomes (analytical skills, planning skills, interpretation skills, and science knowledge) related to the five phases of inquiry-based learning (Orientation, Conceptualization, Investigation, Conclusion, and Discussion) at primary education level (ISCED 1).

Results
A set of contextualized science tasks was created to assess each of the learning outcomes at three levels. The Science Inquiry Test for Primary Education (SIT-PE test) was developed through several phases, including pilot studies with large groups of fourth-grade students (10 to 11 years of age). The 1 PL Item Response Theory model was used to analyze the quality of the test and items based on the test’s reliability score, item difficulty measure, infit and outfit indices, estimation of item discrimination, item-scale correlation, and the quality of the scoring key. The final test, consisting of 24 items, was used with a sample of 1868 students. The analysis showed the SIT-PE test to be of good quality on test level and item level and to also have good predictive validity. Confirmatory factor analysis revealed that the correlated factors model and second-order factor model of the science learning outcomes both had a good fit to data collected with the SIT-PE test. Confirmatory factor analysis confirmed the multidimensionality of science learning outcomes and validated four dimensions of the model: analytical skills, planning skills, interpretation skills, and science knowledge.

Conclusions
In conclusion, the SIT-PE test could be further used for assessing students’ inquiry competence in primary education. However, it could be even further improved in several ways and this study provides guidelines on how to do that. In addition, the SIT-PE provides test developers with information on how to design derivations of the SIT-PE test for assessing particular science inquiry outcomes or the same outcomes in older age groups as well.
Laser microgrooved vs. machined healing abutment disconnection/reconnection: a comparative clinical, radiographical and biochemical study with split-mouth design
Authors: Guarnieri Renzo , Miccoli Gabriele , Reda Rodolfo , Mazzoni Alessandro , Di Nardo Dario , Testarelli Luca 
Published: March 2021

Abstract
Background
Repeated removal and replacement of healing abutments result in frequent injuries to the soft tissues.

Purpose
The purpose of this study was to evaluate the effect of disconnection/reconnection of laser microgrooved vs. machined healing and prosthetic abutments on clinical periodontal parameters, marginal bone levels, and proinflammatory cytokine levels around dental implants.

Material and methods
Twenty-four patients each received 2 implants with one-stage protocol in a split-mouth design on the same jaw. In each patient, one healing and prosthetic abutments with a laser microgrooved surface (LMS group) and one healing and prosthetic abutments with machined surface (MS group) were used. Four months following implant placement (T0), the healing abutments were disconnnected and reconnected three times to carry out the impression procedures and metal framework try-in. Four weeks later (T1), definitive prosthetic abutments were installated with screw-retained crowns. Modified plaque index (mPI), modified gingival index (mGI) bleeding on probing (BOP), and probing depth (PD) were recorded at T0 and T1. At the same time points, samples for immunological analyses were taken from the sulcus around each implant. Peri-implant crevicular fluid (PICF) samples were analyzed for interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α levels using the ELISA kit.

Results
At T0 and T1, mPI and mGI showed no statistical difference between the two groups, while higher PD and BoP values were noted for the MS group (P < 0.05). The mean PICF volume and mean concentrations of IL-1β, IL-6, and (TNF)-α in the LMS group were statistically less than those in the MS group (P < 0.05). In addition, comparison of IL-6 and IL-1β mean concentrations at T0 and T1 in the MS group showed a statistically significant increase (p < 0.05) over time, which was not noted for the LMS.

Conclusion
Disconnection/reconnection of healing and prosthetic abutments with a laser-microgrooved surface resulted in less inflammatory molecular response compared with conventional machined ones.

Trial registration
ClinicalTrials.govNCT04415801, registered 03/06/2020
Mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder: a case report
Authors: Ishikawa Tatsuki , Nakano Katsunori , Osaka Masafumi , Aratani Kenichi , Yayoi Kadotani , Akioka Kiyokazu , Tsuchiya Kuniyuki , Hosokawa Yohei 
Published: March 2021

Abstract
Background
Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare.

Case presentation
We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy.

Conclusions
GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.
An evaluation of the InDevR FluChip-8G insight microarray assay in characterizing influenza a viruses
Authors: Bailey Emily S. , Wang Xinye , Ma Mai-juan , Wang Guo-lin , Gray Gregory C. 
Published: March 2021

AbstractInfluenza viruses are an important cause of disease in both humans and animals, and their detection and characterization can take weeks. In this study, we sought to compare classical virology techniques with a new rapid microarray method for the detection and characterization of a very diverse, panel of animal, environmental, and human clinical or field specimens that were molecularly positive for influenza A alone (n = 111), influenza B alone (n = 3), both viruses (n = 13), or influenza negative (n = 2) viruses. All influenza virus positive samples in this study were first subtyped by traditional laboratory methods, and later evaluated using the FluChip-8G Insight Assay (InDevR Inc. Boulder, CO) in laboratories at Duke University (USA) or at Duke Kunshan University (China). The FluChip-8G Insight multiplexed assay agreed with classical virologic techniques 59 (54.1%) of 109 influenza A-positive, 3 (100%) of the 3 influenza B-positive, 0 (0%) of 10 both influenza A- and B-positive samples, 75% of 24 environmental samples including those positive for H1, H3, H7, H9, N1, and N9 strains, and 80% of 22 avian influenza samples. It had difficulty with avian N6 types and swine H3 and N2 influenza specimens. The FluChip-8G Insight assay performed well with most human, environmental, and animal samples, but had some difficulty with samples containing multiple viral strains and with specific animal influenza strains. As classical virology methods are often iterative and can take weeks, the FluChip-8G Insight Assay rapid results (time range 8 to 12 h) offers considerable time savings. As the FluChip-8G analysis algorithm is expected to improve over time with addition of new subtypes and sample matrices, the FluChip-8G Insight Assay has considerable promise for rapid characterization of novel influenza viruses affecting humans or animals.
Addressing the mental health needs of adolescents in South African communities: a protocol for a feasibility randomized controlled trial
Authors: Sorsdahl K. , van der Westhuizen C. , Neuman M. , Weiss H. A. , Myers B. 
Published: March 2021

Abstract
Background
Like many low- and middle-income countries, almost half of the proportion of the South African population is under the age of 25. Given the peak age of onset for most mental health problems is in adolescence, it is vital that adolescents have access to mental health counselling. There are several initiatives to increase access to mental health counselling in South Africa, primarily through the integration of counselling for common mental disorders (CMD) into primary health care services, but adolescents (15–18 years of age) generally do not utilize these services. To address this gap, we will undertake a study to explore the feasibility of conducting a trial of the effectiveness of a community-based mental health counselling intervention for adolescents at-risk for a CMD.

Methods
The study is a feasibility trial of the ASPIRE intervention, a four-session blended multi-component counselling intervention adapted for South African adolescents at risk for depression and alcohol use disorders. We will enrol 100 adolescents from community settings and randomly assign them to the ASPIRE intervention or a comparison condition. Feasibility measures, such as rates of recruitment, consent to participate in the trial and retention, will be calculated. Qualitative interviews with participants and counsellors will explore the acceptability of the intervention. The primary outcomes for a subsequent trial would be reductions in symptoms of depression and days of heavy drinking which will be measured at baseline, 6 weeks, and 3 months post-randomization.

Discussion
This feasibility trial using a mixed-methods design will allow us to determine whether we can move forward to a larger effectiveness trial of the ASPIRE intervention.

Trial registration
The trial is registered with the Pan African Clinical Trials Registry (PACTR20200352214510). Registered 28 February 2020—retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9795