bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut Microbiome in BALB/c and C57BL/6J Mice Undergoing Experimental Thyroid Autoimmunity Associate with Differences in Immunological Responses and Thyroid Function
Authors: Moshkelgosha Sajad , Masetti Giulia , Berchner-Pfannschmidt Utta , Verhasselt Hedda , Horstmann Mareike , Diaz-Cano Salvador , Noble Alistair , Edelman Barbel , Covelli Danila , Plummer Sue , Marchesi Julian , Ludgate Marian , Biscarini Filippo , Eckstein Anja , Banga J. 
Published: August 2018

AbstractExperimental models of hyperthyroid Graves’ disease (GD) and Graves’ orbitopathy (GO) are efficiently developed by genetic immunisation by electroporation with human thyrotropin hormone receptor (hTSHR) A-subunit plasmid in female BALB/c (H-2d) mice. We investigated susceptibility in C57BL/6 J (H-2b) animals to allow studies on disease mechanisms in transgenic and immune response gene knock-out mice. Higher numbers of female C57BL/6 J were positive for pathogenic thyroid stimulating antibodies, but induced hyperthyroidism remained at a low frequency compared to BALB/c animals. Assessment of hTSHR specific T cells showed reduced proliferation in C57BL/6 J animals accompanied with anti-inflammatory IL-10, with less pro-inflammatory IFN-γ compared to BALB/c. Whilst the orbital tissue from immune BALB/c mice showed inflammation and adipogenesis, in contrast C57BL/6 J animals showed normal pathology. We characterised the gut microbiota using 16 S ribosomal RNA gene sequencing to explore its possible pathogenic role in the model. Despite being housed under identical conditions, we observed significantly different organisation of the microbiota (beta-diversity) in the two strains. Taxonomic differences were also noted, with C57BL/6 J showing an enrichment of Operational Taxonomic Units (OTUs) belonging to the Paludibacter and Allobaculum, followed by Limibacter, Anaerophaga and Ureaplasma genera. A higher number of genera significantly correlating with clinical features was observed in C57BL/6 J compared to BALB/c; for example, Limibacter OTUs correlated negatively with thyroid-stimulating antibodies in C57BL/6 J mice. Thus, our data suggest gut microbiota may play a pivotal immunomodulatory role that differentiates the thyroid function and orbital pathology outcome in these two inbred strains undergoing experimental GO.
Perioperative Management of Endocrine Active Adrenal Tumors
Authors: Schreiner Florentine , Anand Gurpreet , Beuschlein Felix 
Published: August 2018

AbstractEndocrine active adrenal tumors are associated with a relevant risk of complications during surgery, either due to direct hemodynamic effects of the hormone excess or due to hormone related comorbidities. Over the last decades, careful preoperative evaluation and improved peri-interventional medical management of affected patients has resulted in a significant reduction of perioperative complications. In addition, improvement in anesthesia and surgical techniques with the feasibility of laparoscopic adrenalectomy have contributed to reduce morbidity. Nevertheless, there are still several challenges to be considered in the perioperative care of these patients. Due to the rarity of functionally active adrenal tumors, there are no prospective data available to guide clinical management. Accordingly, most recommendations are based on retrospective data analysis, expert opinion or carry weak evidence based on small series or case reports. The aim of this review is to summarize the current knowledge and to suggest practical approaches to reduce perioperative complications in endocrine active adrenal tumors. This review exclusively deals with data from adult patients with functionally active adrenal tumors.
Fallstricke bei der Schmerztherapie von Palliativpatienten
Authors: Himstedt-Kämpfer Bernd 
Published: August 2018

ZusammenfassungEine adäquate Schmerztherapie ist kein Selbstläufer, sondern kann sich in verschiedenen Fallstricken verfangen. Viele Palliativpatienten haben mit Ängsten zu
tun: Angst vor der Zukunft, vor Symptomverschlechterung, vor weiteren Nebenwirkungen, vor einer Abhängigkeit und vor Sterben und Tod. Häufig werden Schmerzen
auch nicht erkannt, entweder weil der Patient nicht darüber spricht oder weil Patienten nicht zur verbalen Kommunikation fähig sind. Dabei können die
verschiedensten Möglichkeiten zur Schmerzlinderung nur adäquat eingesetzt werden, wenn die Schmerzursache möglichst gut geklärt ist. Beim Einsatz von Opiaten
ist dauerhaft eine begleitende Laxanzientherapie indiziert. Die Wirksamkeit und Verträglichkeit von Substanzen variiert von Patient zu Patient. Schmerzen
unterschiedlicher Genese und unterschiedlichen Charakters benötigen unterschiedliche Therapien. Allein aufgrund der komplexen physiologischen und
pathophysiologischen Abläufe bei Schmerzentstehung und Schmerzverarbeitung ist eine Kombination verschiedener analgetischer Interventionen indiziert. Weitere
Elemente einer multimodalen Therapie sind z. B. Physiotherapie, lokale regionale Maßnahmen wie das Kühlen oder Wärmen von schmerzenden Körperstellen sowie
pflegerische Maßnahmen wie Einreibungen, Wickel oder Bäder. Da seelische Nöte und Schmerzen sich gegenseitig verstärken, kann psychologische Unterstützung diese
Nöte auffangen. In Zeiten kurzer Verweildauern ist es wichtig, die Schmerztherapie frühzeitig mit in die Therapieplanung aufzunehmen.Im Folgenden werden häufige Fallstricke aus der klinischen Erfahrung mit Palliativpatienten benannt und es wird beschrieben, wie sie umgangen werden können.
The Abdominal Aortic Intima-Media Thickness Increases in Patients with Primary Hyperparathyroidism
Authors: Sumbul Hilmi Erdem , Koc Ayse Selcan 
Published: August 2018

Abstract
Background We aimed to determine whether there is an increase in aortic intima-media thickness values measured from the abdominal aorta in addition to the traditional carotid intima-media thickness in patients with primary hyperparathyroidism and to determine the parameters closely related to aortic intima-media thickness.
Methods This perspective study included 65 primary hyperparathyroidism patients and 30 healthy-controls. Routine laboratory tests for the diagnosis of hyperparathyroidism and vascular ultrasound examinations were performed. Common carotid, internal carotid, and abdominal aortic intima media thickness were measured. The participants of the study was divided into 3 groups as the control (Group–I), the medical treatment (Group–II) due to primary hyperparathyroidism, and the planned surgery (group–III).
Results Aortic intima-media thickness, serum urea, creatinine, glucose, uric acid, hs-CRP, parathyroid hormone, calcium and urine calcium levels increased significantly from Group–I to Group–III and T–scores and serum phosphorus in levels decreased significantly. Carotid intima-media thicknesses were not significantly different between the groups. Serum and urinary calcium levels were independently associated with aortic intima-media thickness. Aortic intima-media thickness, serum phosphorus, parathyroid hormone, T-scores, serum and urinary calcium levels are independent indicators for Group–III. When the cut-off value of aortic intima-media thickness was taken as 1.5 mm, 80.6% sensitivity and 89.1% specificity were determined for patients who would go to surgery.
Conclusion Serum and urine calcium levels were independently associated with aortic intima-media thickness. Aortic intima-media thickness is more useful than carotid intima-media thickness in showing vascular organ involvement in patients with primary hyperparathyroidism.
The Use of a Game-Based Decision Aid to Educate Pregnant Women about Prenatal Screening: A Randomized Controlled Study
Authors: Johnson Erin , Wong Bob , Rose Nancy , Latendresse Gwen , Altizer Roger , Zagal Jose , Smid Marcela , Watson Abby , Botkin Jeffrey , Rothwell Erin 
Published: August 2018

Purpose This project developed and evaluated the efficacy of a game decision aid among pregnant women about prenatal screening in a randomized controlled study.
Study Design Participants were recruited from an obstetric clinic of an academic urban medical center and randomized (n = 73) to one of two study groups: the control group (n = 39) that used a brochure or the intervention group (n = 34) that also used a game decision aid.
Result Participants who played the game had higher knowledge scores (m = 21.41, standard deviation [SD] = 1.74) than participants in the control group (m = 19.59; SD = 3.31), p = 0.004. The median time of game playing was 6:43 minutes (range: 2:17–16:44). The groups were similar in frequency of completing screening after the study, control = 6 (15%) versus intervention = 11 (32%), p = 0.087. However, the more interaction with the game resulted in more positive attitudes toward screening.
Conclusion The addition of a game decision aid was effective in educating pregnant women about prenatal screening. As other genetic testing decisions continue to increase within clinical care, game-based decision tools may be a constructive method of informed decision-making.
“Behave yourself, woman!”
Authors: Ilie Cornelia 
Published: August 2018

Abstract
After a record number of women were elected to the House of Commons in 1997, many incidents of sexism and abusive behaviour were reported. The aim of this article is twofold: on the one hand, to scrutinize the mechanisms and effects of sexist discrimination and stereotyping of women MPs in the House of Commons; on the other, to identify the strategies used by female (and male) MPs to subvert discriminatory representations, and to counteract gender-biased and sexist treatment. The focus of the multi-level analysis is on three recurrent strategies: objectifying women MPs through fixation on personal appearance rather than professional performance (e.g. making trivialising comments about women’s hair and dressing style); patronizing women MPs through the use of derogatory forms of address (e.g. directly addressing them by the terms of endearment “honey”, “dear”, “woman”); and stigmatizing women MPs through abusive and discriminatory labelling (e.g. ascribing to them stereotypically insulting names.
A Legally Constructed Underclass of Workers? The Deportability and Limited Work Rights of International Students in Australia and the United Kingdom
Authors: Howe Joanna 
Published: August 2018

Abstract
International students have not traditionally been the focus of labour law scholarship, in part because their central purpose in a foreign country is to study rather than work. It is also generally accepted that there is no special reason to focus on international students as a distinct category of workers. This article attests to the particular vulnerability of international students in domestic labour markets, drawing on a comparative study of government policy and practice in relation to international students in Australia and the UK. Immigration rules in both jurisdictions frame the manner in which international students engage in the labour market during their studies. These rules restrict the hours in which international students can engage in paid work during semester, and if breached can result in the international students being deported from the host country. This has the effect of limiting the job market for international students, increasing the power of employers and reducing the likelihood international students will report exploitative work. Instead of strict work hour limits and deportation for breach, governments should rely on other regulatory mechanisms for ensuring international students are present in the host country for the purpose of education rather than work.
Impact of a tailored training on advanced electronic medical records use for providers in a Veterans Health Administration Medical System
Authors: Lopez Christopher A , Omizo Reese K , Whealin Julia M 
Published: August 2018

Abstract
This quality improvement project evaluated the impact of a tailored, evidence-based training strategy on advanced electronic medical record (EMR) use for Veterans Administration (VA) clinicians experienced in using the EMR. After developing the curriculum, an online needs assessment tool evaluated 20 clinicians’ competency gaps. Responses were used to prioritize clinicians’ training needs. Clinician informaticists then provided 2–4 h of tailored training to groups of 1–5 clinicians. Compared with baseline scores (M = 3.59), scores on EMR Task Comfort showed a large improvement in the week following training (M = 4.60; t = 5.41; P &lt;.000, r = 0.58) regardless of baseline level of computer anxiety. Assessment and tailored training methods can help maximize the benefits of resources for EMR training. This formative evaluation suggests that tailored, hands-on training led by clinician informaticists effectively improved clinicians’ EMR comfort and confidence in only 2–4 h.
Nuclear localized Raf1 isoform alters DNA‐dependent protein kinase activity and the DNA damage response
Authors: Nixon Benjamin R. , Sebag Sara C. , Glennon Michael S. , Hall Eric J. , Kounlavong Emily S. , Freeman Michael L. , Becker Jason R. 
Published: August 2018

ABSTRACTRaf1/c‐Raf is a well‐characterized serine/threonine–protein kinase that links Ras family members with the MAPK/ERK signaling cascade. We have identified a novel splice isoform of human Raf1 that causes protein truncation and loss of the C‐terminal kinase domain (Raf1‐tr). We found that Raf1‐tr has increased nuclear localization compared with full‐length Raf1, and this finding was secondary to reduced binding of Raf1‐tr to the cytoplasmic chaperone FK506 binding protein 5. We show that Raf1‐tr has increased binding to DNA‐dependent protein kinase (DNA‐PK), which inhibits DNA‐PK function and causes amplification of irradiation‐ and bleomycin‐induced DNA damage. We found that the human colorectal cancer cell line, HCT‐116, displayed reduced expression of Raf1‐tr, and reintroduction of Raf1‐tr sensitized the cells to bleomycin‐induced apoptosis. Furthermore, we identified differential Raf1‐tr expression in breast cancer cell lines and showed that breast cancer cells with increased Raf1‐tr expression become sensitized to bleomycin‐induced apoptosis. Collectively, these results demonstrate a novel Raf1 isoform in humans that has a unique noncanonical role in regulating the double‐stranded DNA damage response pathway through modulation of DNA‐PK function.—Nixon, B. R., Sebag, S. C., Glennon, M. S., Hall, E. J., Kounlavong, E. S., Freeman, M. L., Becker, J. R. Nuclear localized Raf1 isoform alters DNA‐dependent protein kinase activity and the DNA damage response. FASEB J. 33, 1138–1150 (2019). www.fasebj.org
Noninvasive measures in atopic dermatitis
Authors: Fluhr Joachim W. , Zuberbier Torsten , Darlenski Razvigor 
Published: August 2018

Purpose of review
To summarize the current knowledge on the morphology, functionality and biochemical composition of the skin in allergic reactions. We address novel noninvasive techniques that promise to disclose intimate mechanisms of skin allergy in vivo. Epidermal barrier is not just a static wrap of the organism but rather a dynamic field for immunological, biophysical and biochemical processes and serves as a bio-sensor for exogenous danger signals.

Recent findings
Classical biophysical methods are amended by novel in-vivo techniques, such as Raman spectroscopy, analysing the skin microcomposition and develop epidermal profiles. Visualization techniques, such as reflectance spectroscopy and optical coherence tomography (OCT) are employed in studying the micro-morphological changes in the skin of allergic patients.

Summary
The noninvasive assessment of skin functions, micro-morphology and biochemical as well as immunological pathways will help to better understand skin allergies. They will allow to detect subtypes, for example in atopic dermatitis and to develop specific treatment modalities.
Intraocular Pressure Lowering Effect of Latanoprost as First-line Treatment for Glaucoma
Authors: Aspberg Johan , Heijl Anders , Jóhannesson Gauti , Lindén Christina , Andersson-Geimer Sabina , Bengtsson Boel 
Published: August 2018

Purpose:
The purpose of this study was to assess the intraocular pressure (IOP) - reducing effect of latanoprost in treatment-naïve patients with newly detected open-angle glaucoma with no restriction of the level of untreated IOP.

Methods:
Eighty-six patients (105 eyes) with a diagnosis of open-angle glaucoma received IOP-lowering therapy with latanoprost. The IOP reduction 1 and 3 months after initiation of treatment was recorded.

Results:
Mean untreated IOP for all eyes was 26.2 mm Hg (ranging from 10 to 51 mm Hg). The mean pressure reduction was 7.9 mm Hg (28%), with equivalent average levels at 1 and 3 months. The reduction in IOP ranged from −2.3 to 25.3 mm Hg after 1 month, and from −1.3 to 33.3 mm Hg after 3 months. The pressure-lowering effect was considerably more pronounced in eyes with higher untreated IOP; the reduction increased by 0.55 mm Hg per mm Hg higher untreated IOP. Four eyes, with untreated IOP within statistically normal limits, had no or negative IOP-reduction. A regression model predicted that IOP reduction ended at untreated IOP≤16 mm Hg. Multiple regression analysis showed that an additional IOP-lowering effect of 1.28 mm Hg was achieved in eyes with pseudoexfoliation glaucoma.

Conclusions:
To the best of our knowledge, this paper is the first to report the IOP-reducing effect of latanoprost treatment at all untreated IOP levels in newly detected glaucoma patients. The effect was proportional to the untreated IOP at all levels above 16 mm Hg and better at higher untreated IOP levels, also in relative terms. Our results further confirm the indication of latanoprost as a first-line therapy for glaucoma.
Efficacy of Sertraline in Patients With Major Depressive Disorder Naive to Selective Serotonin Reuptake Inhibitors
Authors: Valle-Cabrera Roselin , Mendoza-Rodríguez Yudexi , Robaina-García Maytee , Ballesteros Javier , Cordero-Jiménez Juan Rafael , Espinosa-Rodríguez Nadia B. , Sotolongo-Garcia Yenia , Lauria-Horner Bianca 
Published: August 2018

Abstract

Purpose
The aim of this study was to assess the efficacy and safety of sertraline compared with placebo in a good clinical practice trial conducted with major depressive disorder patients naive to selective serotonin reuptake inhibitors.

Methods
This was a 10-week randomized, multicenter, placebo-controlled, double blind, superiority trial. Adult patients diagnosed with major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria), total score of 19 to 36 in the 17-item Hamilton Depression Rating Scale (HAMD-17), were randomly allocated to sertraline (n = 39) or placebo (n = 38). Each patient received a fixed dose of sertraline 50 mg/d or placebo for 4 weeks. Afterward a flexible dose up to 200 mg/d was allowed if needed. The primary efficacy end point was clinical response defined as 50% score reduction in HAMD-17 at 10 weeks relative to baseline. Supplementary analysis was performed on HAMD-17 score change from baseline.

Findings
The clinical response favored sertraline (72% vs 32%; relative risk, 2.27; 95% confidence interval, 1.37–3.78; P = 0.0006). A linear mixed model showed arm × time interaction was significant (likelihood ratio test χ2 on 7 df = 48.42, P < 0.0001). The HAMD-17 change score favored sertraline from week 8 onwards. The most frequent adverse events in the sertraline arm were headache, diarrheas, and weight loss.

Implications
In this trial, the benefit of sertraline compared with placebo appeared later than usual. The therapeutic process with a close doctor-patient relationship throughout the trial and the effect expectancy due to a new treatment might explain the response delay.

Trial registration: RPCEC, ID no. 00000128.
Next Generation Sequencing of Sporadic Vestibular Schwannoma: Necessity of Biallelic NF2 Inactivation and Implications of Accessory Non-NF2 Variants
Authors: Carlson Matthew L. , Smadbeck James B. , Link Michael J. , Klee Eric W. , Vasmatzis George , Schimmenti Lisa A. 
Published: August 2018

Objectives:
1) Describe the genetic alterations discovered in a series of sporadic vestibular schwannomas (VS). 2) Identify if more clinically aggressive variants possess different genetic alterations compared to more indolent-behaving VS.

Methods:
Fresh frozen tumor and matched peripheral blood leukocytes from 23 individuals with sporadic VS were analyzed using whole-exome sequencing, tumor whole transcriptome expression profiling (mRNA-Seq), and tumor mate-pair analysis. Source cases included tumors with fast preoperative growth, giant tumors in young patients, tumors with macrocystic change, recurrent tumors following radiation or microsurgery, and indolent small tumors with minimal or no growth before surgery. Somatic and germ-line alterations of the NF2 gene and beyond the NF2 locus were identified and analyzed using complementing analyses.

Results:
Biallelic somatic events involving the NF2 gene were discovered in every analyzed tumor specimen with no concurrent NF2 variants identified in matching peripheral blood specimens. Thirteen tumors showed loss of one chromosome 22 (ch22), 4 tumors showed copy-neutral 22q loss of heterozygosity, and 31 unique small variants in the NF2 gene were discovered. Of the latter, 10 were essential splice site, 11 frame shift, 7 stop gain, 2 missense, and 1 in-frame mutation. No other common or recurring NF2 mutations were identified. However, several other notable large chromosomal aberrations were discovered including 2 tumors with loss of a chromosome 21, 3 with loss of an X or Y chromosome, 1 with copy-neutral loss of heterozygosity in chromosome 15, and 1 with loss of 18p and 16q. All of these other major chromosomal abnormalities only occurred in tumors demonstrating a more aggressive phenotype.

Conclusions:
To date, few studies have used whole-exome sequencing, mate-pair analysis, and RNA-seq to profile genome-wide alterations in sporadic VS. Using high-throughput deep sequencing, “two-hit” alterations in the NF2 gene were identified in every tumor and were not present in peripheral blood supporting that all events were somatic. Type of NF2 gene alteration and accessory mutations outside the NF2 locus may predict phenotypic expression and clinical course.
Cochlear Implantation in Organ Transplant Recipients
Authors: Suhling Marie-Charlot , Lenarz Thomas , Teschner Magnus 
Published: August 2018

Objective:
Immunosuppressed individuals who have undergone organ transplants, especially children, pose particular challenges in terms of treatment. The aim of this study was to analyze the postoperative complication rate of organ transplant recipients who have also received a cochlear implant (CI).

Study Design:
Retrospective case series.

Setting:
Tertiary referral center.

Intervention:
The case series includes 13 kidney, liver, lung, and heart transplant patients. Age at treatment ranged from 2 to 71 years, with a total of 17 CIs.

Main Outcome Measures:
Postoperative complications were classified into major and minor, early (within 3 mo postoperatively) and late (>3 mo postoperatively). The results were compared with those for 13 1:1 matched pairs obtained and from our database and a healthy patient collective from our department.

Results:
The global postoperative complication rate was 29.4%. The proportion of patients suffering major complications was 17.6%, with 17.6% having minor complications. Complications that occurred early accounted for 13.3%, and late for 26.7%. No adults, and 33.0% of children, showed any complications after cochlear implantation. The global complication rate (29.4%) was significantly increased compared with the matched pairs (0%, p = 0.013) and department data (13.8%, p = 0.006; Cramers v = 0.102).

Conclusion:
This study demonstrates that organ transplant recipients, and especially children, are at increased risk of postoperative complications after cochlear implantation in comparison with healthy CI recipients.